LÉKAŘSKÁ FAKULTA MASARYKOVY UNIVERZITY
V BRNĚ
aerobní trénink nemocných s chronickou ischemickou chorobou
srdeční a jeho vliv na systolickou a diastolickou funkci levé komory, toleranci zátěže a prognózu nemocných
(SOUBOR PUBLIKACÍ)
MUDr. Roman Panovský, Ph.D. HABILITAČNÍ PRÁCE
BRNO 2015
Pokládám za milou povinnost poděkovat
svému učiteli:
prof.MUDr.Jaroslavu Meluzínovi, CSc za výchovu, odborné podněty, cenné rady a velkou trpělivost při četných konzultacích
přednostům I.interní kardio-angiologické kliniky:
prof. MUDr.Miloši Štejfovi, DrSc, prof. MUDr. Jiřímu Tomanovi, CSc, prof. MUDr. Jiřímu Vítovcovi, CSc a prof. MUDr. Lence Špinarové, Ph.D. za vytváření prostřední pro vědeckou práci
svým kolegům:
MUDr. Vladimíru Kinclovi, PhD, MUDr. Radkovi Jančárovi a MUDr.Pavlu Kuklovi,
za pomoc při vyšetřování nemocných a při zpracování získaných dat
lékařům a fyzioterapeutkám Kliniky tělovýchovného lékařství a rehabilitace:
především doc.MUDr.Jiřímu Jančíkovi, PhD, Mgr. Leoně Mífkové, Ph.D., Mgr. Lucii Kožantové, Ph.D., kteří pod vedením prof.MUDr.Jarmily Siegelové, DrSc. a prof.MUDr.Petra Dobšáka, CSc. kompletně zajišťovali řízený rehabilitační program nemocných.
OBSAH
1. ÚVOD A CÍLE
1.1. Příznivé účinky aerobního tréninku
1.2. Tréninkové režimy
1.3. Efekt kardiovaskulární rehabilitace na funkci levé komory srdeční
1.4. Cíle práce
1.5. Literatura k úvodním kapitolám
2. VÝSLEDKY - PUBLIKOVANÉ VĚDECKÉ PRÁCE
2.1. Srovnání řízeného a nekontrolovaného aerobního tréninku nemocných
s chronickou ischemickou chorobou srdeční
2.2. The effect of regular physical activity on the left ventricle systolic
function in patients with chronic coronary artery disease
2.3. Assessing the left ventricle diastolic function in group of patients
with chronic ischemic heart disease and regular physical activity
2.4. The prognostic effect of different types of cardiac rehabilitation
in patients with coronary artery disease
3. SOUHRN
4. ZÁVĚR
5. PŘÍLOHY - ORIGINÁLY PUBLIKOVANÝCH PRACÍ
1. ÚVOD
1.1. PŘÍZNIVÉ ÚČINKY AEROBNÍHO TRÉNINKU
Příznivý vliv fyzické aktivity na kardiovaskulární systém je nesporný nejen u zdravých j edinců, ale i u nemocných s kardiovaskulárními chorobami. Již desítky let je známo, že pravidelná aerobní zátěž nemocným se srdečními chorobami zlepšuje kvalitu života, omezuje jejich symptomy a zejména snižuje mortalitu [1-9]. Děje se tak ovlivněním celé řady dějů v organismu. Zřejmě nej výraznější m účinkem je příznivé ovlivnění rizikových faktorů ischemické choroby srdeční (ICHS) [10-11]. Je ovlivněn lipidový metabolismus snížením LDL (low-density lipoprotein) a zvýšením HDL (high density lipoprotein) cholesterolu [8, 12-14]. Pravidelnou tělesnou aktivitou dochází též ke zvýšení senzitivity k inzulínu, což spolu s dietními opatřeními vede k redukci obezity [8, 15]. Dalším efektem je ovlivnění humorální rovnováhy snížením klidové sympatikoadrenální aktivity [16]. Tento vliv spolu s omezením agregace krevních destiček a poklesem plazmatických hladin fibrinogenu vede ke snížení rizika vzniku akutního koronárního syndromu. Menší vzestup tepové frekvence (TF) a krevního tlaku (TK) při zátěži způsobuje pokles kyslíkových požadavků myokardu [17-20]. V neposlední řadě je příznivě ovlivněna i psychika nemocných [8].
Výše popsané účinky jsou více či méně společné pro jakoukoliv skupinu cvičících, ať už se jedná o primární prevenci zdravých jedinců nebo sekundární prevenci kardiologický nemocných. U nemocných s ICHS jsou kromě zlepšení prognózy nemocných [21-23] očekávány i některé specifické efekty aerobního tréninku. Jde především o zmírnění anginózních potíží a objektivních známek ischemie myokardu při zátěžových testech - zvýšení tolerance zátěže, snížení incidence depresí ST úseku při zátěžovém testu nebo segmentární poruchy kontraktility při zátěžové echokardiografii, apod. [24-25]. Tyto změny mohou nastat několika mechanismy. Pravidelný trénink vede jednak snížení srdeční práce tím, že se na jedné straně sníží spotřeba kyslíku (snížením TF a TK) [7, 26-29] a zároveň dochází i ke zlepšení přísunu kyslíku (rozšířením epikardiálních koronárních artérií, zvýšením denzity myokardiálních kapilár a případným rozvojem kolaterál) [24, 30]. Kombinace pravidelného cvičení s dietou omezující tuky vede u nemocných s ICHS ke zpomalení progrese koronárních stenóz a podle některých prací může dokonce dojít až kjejich regresi [17, 28, 31-32].
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1.2. TRÉNINKOVÉ REŽIMY
Z výše uvedeného je zřejmé, že by kardiovaskulární rehabilitace měla představovat nezbytnou součást komplexní léčby pacientů s ICHS. Je také součástí mnoha doporučení odborných společností. Aktuálně platná doporučení České kardiologické společnosti z roku 2006 [33] popisují u nemocných s ICHS rehabilitaci nemocných po infarktu myokardu (IM), kterou rozdělují na 4. fáze - nemocniční, časnou posthospitalizační, stabilizační a udržovací. Dále se zaobírají jinými kardiálními diagnózami. Nemocní s chronickou ICHS zde nejsou blíže rozvedeni. Novější doporučení Evropské kardiologické společnosti [34] rozebírají obecně nemocné se srdečními onemocněními s důrazem na nemocné po UVI, aortokoronárních bypassech (CABG) nebo koronárních intervencích (PCI). Naproti tomu, americká doporučení American Heart Association [35] jsou zaměřena cíleně na nemocné s koronárni nemocí. Podle těchto doporučení by všichni nemocní měli být povzbuzováni a motivováni k 30-60 minutám středně intenzivní aerobní aktivity nejméně 5 (nejlépe 7) dní v týdnu. Je vhodné tento aerobní trénink podpořit silovým cvičením alespoň 2krát týdně.
Ačkoliv je prospěšnost kardiovaskulární rehabilitace nezpochybnitelná, není zatím zcela vyjasněno přesné optimální nastavení tréninku. Struktura a intenzita doporučovaných a realizovaných tréninků se liší nejenom mezi jednotlivými zeměmi, ale i mezi centry. Odlišnosti jsou prakticky ve všech parametrech tréninku - intenzitě, frekvenci, trvání, obsahu tréninkové jednotky. Tomuto faktu odpovídá i výrazná nesourodost publikací ve světové vědecké literatuře s nemožností srovnaní dat z různých center a obtížemi stran praktických aplikací zjištěných výsledků [36-39]. Je jistě správné, aby nemocný měl (víceméně jakékoliv) navýšení hlavně aerobní aktivity, ale určitě v současné době existuje poměrně velký prostor pro snahy hledat optimální tréninkový režim.
Jakkoliv je hledání optimálního tréninkového modelu důležité, daleko větším aktuálním problémem je relativně malé procento nemocných, kteří se institucionálních tréninkových programů účastní. Příčiny jsou jak na straně medicínských zařízení, tak na straně pacientů. Ne každá nemocnice má k dispozici oddělení kardiovaskulární rehabilitace. A i v případech, že tato možnost existuje, jen málokde je celý systém natolik fungující, aby byli všichni nemocní osloveni a motivováni k absolvování tréninkových jednotek. A z těch, kterým účast nabídnuta je, jen menší část nemocných s absolvováním ambulantních cvičení souhlasí a opravdu ho celé absolvuje. Důvody jsou pestré, od
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principiální nechuti nemocného měnit svůj zavedený životní styl až po důvody ryze praktické, zahrnující například časovou náročnost, problémy s dopravováním se na trénink, apod. Pro tyto nemocné jsou ve světě hledány alternativy. Jednou z možností je takzvaná domácí rehabilitace, kdy nemocný není nucen dojíždět do centra, ale cvičí si sám doma. Domácí rehabilitace může být výhradním tréninkem nebo může navazovat na vstupní tréninkové jednotky v centru. Může být pod částečným dozorem (skrze telefonní kontakt nebo internet) nebo bez dozoru s následným zhodnocením při ambulantní kontrole nemocného [40-43]. Domácí rehabilitace má řadu výhod, ale také limitací. Mezi omezení patří zejména horší kontrola cvičení a omezená možnost pomoci nemocnému při případných nežádoucích účincích cvičení - proto nelze tento druh tréninku doporučit paušálně všem nemocným. K hlavním výhodám patří kromě již zmíněného vyřešení některých překážek absolvování cvičení i to, že pacient, který si zvykne na režim v domácích podmínkách, v tomto režimu snadněji setrvá v budoucnu. Dosud nejsou jednoznačná data srovnávající efekt řízeného a individuálního aerobního cvičení.
1.3. EFEKT KARDIOVASKULÁRNÍ REHABILITACE NA FUNKCI LEVÉ KOMORY (LK) SRDEČNÍ
Jak bylo uvedeno na začátku, existuje poměrně velké množství dat potvrzujících nej různější příznivé účinky kardiovaskulární rehabilitace. Oproti tomu máme k dispozici jen omezené množství informací o tom, zda trénink dokáže ovlivnit funkci LK. Výsledky dostupných prací u nemocných s ICHS jsou rozporuplné. Na jedné straně řada prací [44-47] nenašla žádný významný rozdíl mezi skupinami cvičícími a kontrolními. Na straně druhé, například Giannuzzi s kolektivem [48] zjistili zlepšení ejekční frakce (EF) LK a redukci nežádoucí remodelace LK u nemocných po Q EVI a absolvování tréninku ve srovnání s kontrolami bez tréninku. Podobně Klecha a spol. [49] popsali trend ke zlepšení funkčních parametrů LK po šestiměsíčním tréninku nemocných s ICHS. Podobné výsledky publikovali i další autoři [50-51]. Podle velké metaanalýzy z roku 2011 [52] bylo nalezeno celkem 12 studií zkoumající efekt tréninku na EF LK u nemocných po JJVI. Metaanalýza potvrdila pozitivní efekt rehabilitace jak na vývoj EF LK, tak i na její remodelaci.
LK hodnocen pomocí EF LK a endsystolického a enddiastolického rozměru LK.
Výhodou těchto parametrů je jejich snadná dostupnost a také fakt, že jsou rutinně
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používány. Naopak nevýhodou je, že jsou na sledování malých změn (ajiné se jistě při krátkých sledováních ani očekávat nedají) příliš hrubými parametry. Lze spekulovat o tom, že v studiích s negativním výsledkem mohl být příznivý efekt rehabilitace na funkci a remodelaci LK přítomný, ale natolik malý, že pomocí měřených parametrů prostě nebyl zachycen.
Novější echokardiografická metoda, tkáňová dopplerovská echokardiografie (TDI) je technika využívající dopplerovský princip k měření rychlosti pohybu myokardu. Pulsní TDI umožňuje výrazně přesněji kvantifikovat systolickou i diastolickou funkci LK [53-55]. Parametry TDI se tedy nabízí jako potenciálně výhodnější a přesnější k sledování zejména menších změn funkce LK v čase [56]. Pomocí pulsní TDI získáme křivku pohybu myokardu v měřeném místě. Měření lze provádět prakticky v jakémkoliv segmentu LK, ale pro praxi se nejlépe osvědčilo měření rychlostí myokardu na bazi jednotlivých stěn v těsné blízkosti mitrálního anulu. Vzhledem k fyziologickým principům srdeční kontrakce je měření v těchto místech obrazem funkce celé příslušné stěny. Regionální systolická funkce je pak hodnocena velikostí vlny Sa (nově označované jako S'), která ukazuje aktuální rychlosti myokardu během systoly. V diastole měříme (u pacientů se sinusovým rytmem) vlnu Ea (nově E' nebo e'), která zachycuje rychlosti myokardu během fáze rychlého plnění komory, a vlnu Aa (A'nebo a') odpovídající rychlosti myokardu v době kontrakce síně. K vlastnímu hodnocení diastolické funkce je pak použita buď velikost vlny Ea nebo poměr vln Ea/Aa.
Do této dobyje v písemnictví jen velmi málo prací, které využívají pulsní TDI k hodnocení efektu kardiovaskulární rehabilitace na funkci LK. Jedna práce [57] popisuje zlepšení diastolické funkce hodnocené pomocí TDI u obézních mužů po osmitýdenním tréninku, další [58] zlepšení diastolické funkce LK po komplexní intervenci včetně tělesného tréninku u nemocných s ledvinným selháním. U nemocných s ICHS po EVI, Deljanin-Ilic a spol. [59] popsali po tréninku zlepšení celkové i regionální funkce LK v místě LVI.
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1.4. CÍLE HABILITAČNÍ PRÁCE
(1) Srovnat parametry opakovaného ergometrického zátěžového testu nemocných s ICHS s řízeným a nekontrolovaným aerobním tréninkem.
(2) Zhodnotit vliv aerobního tréninku na systolickou a diastolickou funkci LK u nemocných s ICHS.
(3) Porovnat prognostický efekt různých typů tréninku.
Tyto cíle vyly řešeny v dílčích projektech, které jsou uvedeny v následujících kapitolách 2.1.,2.2.,2.3.a2.4.,a které byly úspěšně publikovány v recenzovaných kardiologických časopisech.
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2. VÝSLEDKY
2.1. SROVNÁNÍ ŘÍZENÉHO A NEKONTROLOVANÉHO AEROBNÍHO TRÉNINKU NEMOCNÝCH S CHRONICKOU ISCHEMICKOU CHOROBOU SRDEČNÍ
ABSTRAKT
Cíl: Cílem práce bylo srovnat parametry opakovaného ergometrického zátěžového testu nemocných s chronickou ischemickou chorobou srdeční (ICHS) s řízeným a nekontrolovaným aerobním tréninkem.
Soubor pacientů a metodika: Šedesát čtyři nemocných s chronickou ICHS bylo rozděleno do 4 skupin podle intenzity a druhu aerobního tréninku. Do skupiny A bylo zařazeno 17 pacientů, kteří se zúčastnili řízeného tříměsíčního rehabilitačního programu a navázali na něj individuálním cvičením. Ve skupině B bylo 22 pacientů, kteří absolvovali jen řízený program bez následného individuálního tréninku. Ve skupině C bylo 10 pacientů, kteří neabsolvovali rehabilitační program, ale doma intenzivně cvičili. Do skupiny D bylo zařazeno 15 pacientů, kteří se nezúčastnili rehabilitačního programu, ani doma necvičili. Ergometrické testy byly provedeny před zařazením do studie a po 1 roce sledování. Byly hodnoceny změny těchto parametrů: celkový čas zátěže, celkově vykonaná práce, pracovní kapacita, pracovní tolerance, čas do stenokardií, deprese ST úseku ve svodu V5 při maximální zátěži.
Výsledky: Pro nemocné ve skupině C byl zjištěn trend ke zlepšení ve všech hodnocených parametrech s výjimkou prohloubení deprese úseku ST ve svodu V5 při maximální zátěži. Ve skupině A nemocní dosáhli delšího celkového času zátěže, vykonali větší celkovou práci a měli vyšší pracovní toleranci, v ostatních parametrech došlo ke zhoršení. Pacienti ze skupin B a D se zhoršili ve všech parametrech. Všechny rozdíly v jednotlivých skupinách ani mezi skupinami navzájem nebyly statisticky významné.
Závěry: Parametry opakovaného ergometrického testu nemocných podstupujících jednotlivé typy rehabilitačních programů se od sebe statisticky nelišily. Byl nalezen trend
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ke zlepšení zátěžových parametrů u skupin nemocných cvičících intenzivně a trvale doma a trend ke zhoršení u skupin individuálně necvičících, a to nezávisle na absolvování úvodního řízeného rehabilitačního programu.
Klíčová slova: Tělesný trénink - Ischemická choroba srdeční - Ergometrie
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ÚVOD
Příznivý vliv fyzické aktivity na kardiovaskulární systém je nesporný nejen u zdravých j edinců, ale i u nemocných s kardiovaskulárními chorobami. Pravidelná aerobní zátěž nemocným se srdečními chorobami zlepšuje kvalitu života, omezuje jejich symptomy a snižuje mortalitu [1-8]. Děje se tak příznivým ovlivněním rizikových faktorů vzniku a progrese především ischemické choroby srdeční. Dochází k ovlivnění lipidového metabolismu snížením LDL a zvýšením HDL cholesterolu [5, 9-10]. Zvyšuje se také senzitivita k inzulínu a spolu s dietními opatřeními dochází k redukci obezity [5, 11]. Dochází ke snížení klidové sympatikoadrenální aktivity, což spolu se omezením agregace krevních destiček a poklesem plazmatických hladin fibrinogenu vede ke snížení rizika vzniku akutního koronárního syndromu.
U nemocných s ischemickou chorobou srdeční má pravidelné cvičení řadu příznivých účinků vedoucích ke zmírnění anginózních potíží i objektivních známek ischemie myokardu při zátěžových testech - zvýšení tolerance zátěže, snížení depresí ST úseku, atd. Tyto změny jsou způsobeny několika mechanismy - pravidelný trénink způsobuje jednak snížení srdeční práce tím, že se sníží spotřeba kyslíku (snížením tepové frekvence a krevního tlaku) [4, 12-16] a zároveň má vliv i na zlepšení přísunu kyslíku (rozšířením epikardiálních koronárních artérií, zvýšením denzity myokardiálních kapilár a rozvojem kolaterál) [17-18]. Při dostatečně intenzivní zátěži, spolu s redukcí ostatních rizikových faktorů, může dojít k zastavení progrese popřípadě i k mírné regresi angiografických změn na koronárních artériích [4, 13, 19-20].
Pro pacienty se hledají optimální druhy a režimy tréninku (např. aerobní trénink s posilováním nebo bez něj), různé frekvence a délky cvičení. Prakticky všechny práce hodnotící nej různější řízené tréninkové programy přinášejí důkazy o jejich příznivých efektech. Existuje ale i dostatek prací, které popisují zlepšení pacientů, kteří se o svůj pohybový režim starají více či méně sami Dosud chybí studie srovnávající řízený a individuálního nekontrolovaného aerobního cvičení. Proto bylo cílem této práce srovnat parametry opakovaného ergometrického zátěžového testu nemocných s chronickou ischemickou chorobou srdeční s řízeným a nekontrolovaným aerobním tréninkem.
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MATERIÁL A METODY
Do studie bylo zařazeno 64 nemocných s chronickou ischemickou chorobou, kteří splňovali následující kritéria: onemocnění koronárních tepen bylo ověřeno koronarografií (zúžení průměru lumina tepny > 50% na alespoň 1 hlavní koronárni tepně); bez anamnézy prodělané ataky nestabilní anginy pectoris nebo infarktu myokardu v posledních 3 měsících před zařazením do studie; bez anamnézy revaskularizace myokardu koronárni angioplastikou nebo aortokoronárním bypassem v posledních 3 měsících před zařazením do studie; nepřítomnost významné chlopenní vady a destabilizované hypertenze. Všem nemocným byl opakovaně a důkladně vysvětlen příznivý účinek tělesné aerobní aktivity na jejich zdravotní stav, doporučena pravidelná aerobní aktivita a nabídnut tříměsíční řízený rehabilitační program. Všichni nemocní podstoupili ergometrický zátěžový test při zařazení do studie a po 1 roce sledování.
Zpětně byli nemocní rozděleni do čtyř skupin podle intenzity a druhu jejich aerobního tréninku. Do skupiny A bylo zařazeno 17 pacientů (14 mužů a 3 ženy, průměrného věku 66±11 let), kteří se zúčastnili řízeného rehabilitačního programu a doma na něj navázali individuálním cvičením. Ve skupině B bylo 22 pacientů (14 mužů a 8 žen, průměrného věku 66±8 let), kteří absolvovali jen řízený program bez následného individuálního tréninku. Ve skupině C bylo 10 pacientů (7 mužů a 3 ženy, průměrného věku 60±8 let), kteří neabsolvovali rehabilitační program, ale doma intenzivně cvičili. Do skupiny D bylo zařazeno 15 pacientů (12 mužů a 3 ženy, průměrného věku 63±8 let), kteří se nezúčastnili rehabilitačního programu, ani doma necvičili. Další charakteristiky jednotlivých skupin jsou uvedeny v tabulce 1. Rozdíly mezi jednotlivými skupinami nebyly statisticky významné. Farmakologickou léčbu nemocných ukazuje tabulka 2.
Tabulka 1. Charakteristika pacientů
Tab. 1. Charakteristiky pacientů.
skupina	počet	věk (roky)	nadváha (%) HT {%)		DM {%)	DLP {%)	AP	IM (%)	počet tepen	C AB G (%)	PTCA (%)	EF(%)
A	17	66	71	65	24	82	1,2	53	2,3	18	41	48
B	22	66	82	45	23	82	1.3	86	1,6	14	41	45
C	10	60	80	70	20	90	1,3	90	1,9	20	70	43
D	15	63	67	73	20	73	1.4	60	2.2	20	27	49
HT = hypertenze, DM - diabetes mellitus, DLP = dyslipoprotienemie, AP = stupeň anginy pectoris podle kanadské klasifikace (CCS), IM = počet nemocných po infarktu myokardu, počet tepen - průměrný počet tepen postižených významnou stenozou CABG - počet nemocných po aortokoronárním bypassu, PTCA = počet nemocných po perkutánní koronárni angioplastice, EF = ejekčni frakce levé komory.
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HT = hypertenze; DM = diabetes mellitus; DLP = dyslipoproteinémie; AP = stupeň anginy pectoris podle kanadské klasifikace (CCS); LVI = počet nemocných po infarktu myokardu; Počet tepen = průměrný počet tepen postižených významnou stenózou; CABG = počet nemocných po aorto-koronárním bypassu; PTCA = počet nemocných po perkutánní koronárni angioplastice; EF = ejekční frakce levé komory
Tabulka 2. Charakteristika pacientů - farmakologická léčba nemocných Tab. 2. Farmakologická léčba nemocných.
Skjpina salicvláty {%) BB<%)   CaA(%)  nitráty (%) ACEI (%)   ATII (%) statiny(ä)
A	100	94	53	53	53	12	as
B	96	100	27	63	Ě8	0	82
C	33	100	10	70	70	10	80
□	100	93	40	80	G3	0	73
B B = betablokátory. CaA = kalciový antagonisté, ACEI = antagonisté angiotenzin-konvertujíciho enzymu, ATII = sartany.
BB = betablokátory; CaA = kalciový antagonisté; ACEI = antagonisté angiotenzin konvertují čího enzymu; AT II = sartany
Řízený rehabilitační program probíhal na Klinice funkční diagnostiky a rehabilitace Fakultní nemocnice U svaté Anny. Nemocní, kteří souhlasili s absolvováním tohoto programu, měli před jeho zahájením provedeno spiroergometrické vyšetření k nastavení úrovně aerobního cvičení. Vyšetření bylo provedeno v ranních hodinách při ponechané medikamentózni léčbě. Vlastní vyšetření začínalo tříminutovou adaptací vsedě na veloergometru. Následovaly dvouminutové zátěže od 20 W, zvyšované vždy o 20 W, v jejichž průběhu byly měřeny ventilačně-respirační parametry. Ty byly sledovány přístrojem Pulmonary Function System 1070 (Med Graphics, USA). Byl hodnocen symptomy limitovaný minutový příjem kyslíku (V02) jako kritérium kardiorespirační funkční zdatnosti a byla určena hodnota anaerobního prahu k nastavení vhodné intenzity zatížení. Hodnota anaerobního prahu byla pro potřeby studie vyjádřena ve W, odpovídající hodnotě tepové frekvence a stupněm Borgovy škály subjektivního vnímání namáhavosti
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příslušného zatížení. Během celého vyšetření včetně doby restituce byl monitorován dvanácti svodový elektrokardiogram (Schiller C S 100, USA), v klidu a na konci každé zátěže byl měřen krevní tlak.
Vlastní rehabilitační program trval 3 měsíce, během kterých nemocní cvičili 3x týdně 60 minut. Cvičební jednotka se skládala z fáze zahřívací (10 minut), vlastního aerobního cvičení na veloergometru na úrovni aerobního prahu doplněná silovým tréninkem (40 minut) a ze závěrečné fáze relaxační (10 minut) (Obr. 1).
Individuální aktivita byla doporučována jako minimálně 3krát týdně 60 minut aerobního cvičení (jízda na kole nebo na rotopedu, běh, plavání). Plnění tohoto doporučení bylo zjišťováno pouze anamnestický od pacienta a nebylo ani kontrolováno, ani prověřováno.
Ergometrické zátěžové testy byly provedeny na přístroji Ergo-line před zařazením do studie a po jednom roce sledování, vždy s vysazenou medikací. Bylo započato zátěží 0,5W/kg, která byla schodovitě zvyšována po 3 minutách vždy o 0,5 W/kg. Test byl ukončen při průkazu ischemie (objevení se nebo prohloubení depresí ST úseku o alespoň 0,2mV), při dosažení průměrné maximální tepové frekvence vzhledem k věku, při vzestupu krevního tlaku nad 250/130, při dosažení hranice subjektivního maxima. Rozdíl mezi zátěžovým testem na konci sledování a na začátku studie byl hodnocen pomocí změny těchto parametrů: celkový čas zátěže, celkově vykonaná práce, pracovní kapacita, pracovní tolerance, čas do stenokardií a deprese ST úseku ve svodu V5 při maximální zátěži (srovnáno dle maximální zátěže vstupního testu).
Ejekční frakce byla před zařazením do studie stanovena retrográdní levostrannou ventrikulografií.
Výsledky srovnání změny parametrů ergometrických testů nemocných j sou uvedeny jako průměry ± směrodatná odchylka. Výsledky jednotlivých skupin byly porovnány parametrickou statistickou metodou ANOVA. Hodnoty p < 0,05 byly považovány za významné. Normální rozložení hodnot bylo testováno pomocí Kolmogorov-Smirnovovým testem s výsledkem p > 0.2.
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Obrázek 1. Rehabilitační program
a- zahřívací fáze, b- aerobního cvičení na veloergometru, c- silový trénink, d- relaxační fáze
VÝSLEDKY
Vliv různých typů tréninku na změnu parametrů ergometrického zátěžového testu přehledně znázorňují grafy 1-6.
Graf 1. Srovnání změn celkového času zátěžového testu na konci sledování ve srovnání se vstupním testem v jednotlivých skupinách.
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Graf 2. Srovnání změn celkové práce během zátěžového testu na konci sledování ve srovnání se vstupním testem v jednotlivých skupinách
Graf 3. Srovnání změn času do stenokardií během zátěžového testu na konci
sledování ve srovnání se vstupním testem v jednotlivých skupinách
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Graf 4. Srovnání změn depresí ST úseku ve svodu V5 při maximální zátěži na konci
sledování ve srovnání se vstupním testem v jednotlivých skupinách
Graf 5. Srovnání změn pracovní kapacity na konci sledování ve srovnání se
vstupním testem v jednotlivých skupinách
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Graf 6. Srovnání změn pracovní tolerance na konci sledování ve srovnání se
vstupním testem v jednotlivých skupinách
Nalezené změny zátěžových testů v jednotlivých skupinách nedosáhly statistické významnosti. Nemocní cvičící od začátku individuálně (skupina C) měli trend ke zlepšení ve všech hodnocených parametrech s výjimkou prohloubení deprese úseku ST ve svodu V5 při maximální zátěži (prohloubení při kontrolním testu o 0,006±0,018mV - p=NS). Při kontrolním testu dosáhli o 30±108sec delší doby zátěže, vykonali o 3,7±15,0 kW větší celkovou práci, dosáhli vyšších hodnot pracovní kapacity o 0,01±0,52 W/kg a pracovní tolerance o 0,16±0,33 W/kg a prodloužil se u nich čas do stenokardií o 72±408 sekund (vše p=NS).
Nemocní, kteří absolvovali řízený program a následně individuálně cvičili (skupina A) dosáhli nevýznamně delšího celkového času zátěže (zlepšení o 26±73sec), vykonali větší celkovou práci (o 4,8±14,2 kW) a měli vyšší pracovní toleranci (o 0,03±0,36 W/kg) (vše p = NS). V ostatních parametrech došlo k mírnému zhoršení - pracovní kapacita poklesla o 0,06±0,48 W/kg, ST deprese ve svodu V5 při maximální zátěži se prohloubily o 0,002±0.014 mV a doba do vzniku stenokardií se zkrátila o 95±269 sec (vše p= NS).
Pacienti necvičí vůbec (skupina D) nebo necvičící po absolvování RHB programu (skupina B) se zhoršili prakticky ve všech sledovaných parametrech. Pacienti ve skupině B
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vydrželi kontrolní zátěžový test o 28±51 sec kratší dobu, vykonali o 3,5±5,9 menší celkovou práci, zhoršili svoji pracovní kapacitu o 0,06±0,28 W/kg a pracovní toleranci o 0,08±0,20 W/kg a stenokardie popisovali o 93±219 sec (vše p= NS). Menší deprese úseku ST ve svodu V5 o 0,009±0,018mV (p=NS) je dán menší celkovou prací při kontrolním testu.
Nemocní ze skupiny D měli nižší čas zátěže o 8±95 sec, menší celkově vykonanou práci o 0,8±13,3 kW, menší pracovní kapacitu o 0,23±0,36 W/kg a pracovní toleranci o 0,07±0,25 W/kg, stenokardie udávali o 127±320sec dříve a deprese úseku ST ve svodu V5 se prohloubily o 0,009±0,012 mV (vše p= NS).
Rozdíly mezi jednotlivými hodnocenými skupinami nebyly statisticky významné. Během obou sledovaných forem fyzického tréninku nenastala žádná závažná komplikace.
DISKUSE
V naší práci se parametry opakovaného ergometrického zátěžového testu nemocných s chronickou ischemickou chorobou srdeční podstupující jednotlivé typy rehabilitačních programů od sebe statisticky významně nelišily. Počty nemocných a změny hodnocených parametrů nebyly dostatečně velké k dosažení statisticky významných rozdílů, nicméně byly nalezeny jasné trendy k většímu zlepšení zátěžové kapacity a tolerance u skupin nemocných cvičících intenzivně a trvale doma a to nezávisle na absolvování řízeného rehabilitačního programu.
Nebylo překvapením, že se zlepšili právě pacienti, kteří se cvičení věnují intenzivně sami. Mírně překvapil fakt, že se na výsledcích více neprojevil vstupní řízený trénink. Je tomu tak, pravděpodobně, z důvodů provedení kontrolních testů až 9 měsíců po ukončení řízeného tréninku. Je známo, že čím je trénink více intenzivní, tím se dá očekávat výraznější efekt na zátěžovou toleranci [21]. Zatímco u nemocných, kteří po absolvování programu pokračovali ve cvičení, se při kontrolních testech projevil hlavně intenzivní dlouhodobý trénink. Naopak, ti pacienti, kteří cvičit přestali, měli své funkční parametry na úrovni, jako kdyby necvičili vůbec.
I v ostatních studiích zaměřených na tuto problematiku v minulosti byly nalezeny
vlivy pravidelného cvičení na zátěžové parametry. Studie European Heart Failure
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Training Group [22] uvádí statisticky významné 17% zvýšení celkového času zátěže u pravidelně cvičících pacientů a to bez rozdílu zda účastníci cvičili doma nebo v nemocnici. Také udává větší účinnost u kombinace cvičení na ergometru a rytmiky oproti samotnému cvičení na ergometru.
Benzer a spol. [23] zjistili významné zlepšení stavu (sledované pomocí dotazníku kvality života) po 1-měsíčním cvičení oproti nemocným, kteří necvičili. Zlepšení se sice týkalo jak nemocných cvičících pod dozorem v nemocnici, tak i těch, kteří cvičili individuálně mimo nemocnici, ale individuálně cvičící se zlepšili více. Autoři doporučují nemocným podstupující nemocniční trénink, aby následně navázali individuální aktivitou. Individuální tělesnou aktivitou se zabývali i Adachi a spol. [24], kteří zkoumali vliv různých intenzit tréninku na funkci levé komory. Jejich pacienti cvičili doma - jejich úkolem bylo chodit rychlou chůzí 15 minut 2x denně, 5 dní v týdnu, po dobu 2 měsíců. Intenzitu zátěži si řídili podle tepové frekvence. U 29 nemocných po infarktu myokardu prokázali, že trénink jakékoliv intenzity zlepšuje pracovní kapacitu, ale pouze trénink o vysoké intenzitě zlepšuje funkci levé komory vyjádřenou tepovým objemem a ejekční frakcí. I jiné studie prokázali, že čím je trénink intenzivnější, tím větší je jeho kardioprotektivní účinek [25-26].
Na poměrně velkém souboru 113 pacientů s ICHS, kteří cvičili pravidelně denně doma na rotopedu a své cvičení si zapisovali do přiděleného log-booku, Niebauer se spolupracovníky [13] prokázali po 6 letech sledování 28% zvýšení pracovní kapacity a zpomalení progrese koronárních stenóz. K podobným výsledkům dospěli i další studie [27]. Hledají se také nejrůznější možnosti, jak zvýšit motivaci pacientů ke cvičení a zároveň umožnit lékaři přesnější sledování fyzické aktivity - kromě zmíněného log-booku je možno využít například krokoměr nebo akcelerometr [28-30]. Pravidelné cvičení neovlivňuje pouze fyzickou výkonnost, ale i celkovou kvalitu života. Focht se spolupracovníky [31] porovnávali 2 druhy tělesného tréninku (pouze řízený versus řízený následovaný individuálním cvičením) u 147 osob starších 50 let a dle dotazníků zjistili zlepšení kvality života (health-related quality of life) při obou typech tréninku.
Naše práce, ve shodě s výše uvedenými studiemi, ukazuje, že nej důležitější je pravidelnost a kontinuita cvičení. Řízené rehabilitační programy mají přesto několik nezastupitelných úloh. Ukazují nemocným styl cvičení, posilováním jim umožňují
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dosáhnout lepší fyzické kondice, která je nutná pro další pokračování ve cvičení na dostatečné úrovni zátěže doma. Velmi významná je u pacientů, u kterých hrozí zdravotní komplikace už při malém stupni zátěže a je u nich velké riziko zdravotních komplikací, které vyžadují lékařský dohled popřípadě intervenci. Jedno z možných řešení, jak spojit řízenou a individuální tělesnou aktivitu, naznačují němečtí autoři z Heidelbergu - jejich pacienti cvičili nejdříve 3 týdny intenzivně v nemocnici (6x denně!), následně jim byl zapůjčen rotoped a cvičili individuálně doma (2x denně po 30 minutách) s pravidelnými společnými cvičeními v nemocnici (2x týdně). Tímto velmi intenzivním tréninkem dosáhli u svých pacientů za 12 měsíců nejenom snížení zátěží vyvolané ischemie o 54% [32], ale prokázali i zpomalení progrese koronárni aterosklerózy [20]. Rovněž zastavení progrese koronárních aterosklerotických lézí prokázali Hambrecht a spol. [33] u 29 chronických ischemiků pomocí 12-měsíčního individuálního tréninkového programu (minimálně 30 minut denně jízdy na ergometru) zahájeného 3 týdny společného cvičení v nemocnici (6x denně 10 minut šlapání na ergometru).
Podobně Hofman-Bang [4] nabídli svým pacientům 12 měsíční individuální tréninkový program spoj ený s pokusem o změnu životního stylu, který zahrnoval vstupní 4-týdenní „zaučení". Na 151 nemocných po PTC A (perkutánní transluminální koronárni angioplastice) ukázali zvýšení pracovní kapacity a snížení počtu hospitalizací během následujících 12 měsíců po ukončení programu. Z hlediska praktického využití mají tyto rehabilitační modely zásadní limitaci ve vstupní tří-, respektive čtyřtýdenní hospitalizaci, nicméně jistě by se podobné spojení řízené a individuální aktivity dalo přizpůsobit reálným možnostem a komfortu pacientů.
Hlavními limitacemi naší práce je malé množství nemocných v jednotlivých skupinách a krátká doba sledování. Spolu s očekávaně nevelkými změnami jednotlivých ergometrických parametrů po 1 roce sledování se nedá předpokládat statistická významnost rozdílů mezi skupinami.
ZÁVĚR
Parametry opakovaného ergometrického zátěžového testu nemocných podstupující jednotlivé typy rehabilitačních programů se od sebe statisticky významně nelišily. Byl
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nalezen trend zlepšení zátěžových parametrů u skupin nemocných cvičících intenzivně a trvale doma a trend zhoršení u skupin individuálně necvičících, a to nezávisle na absolvování úvodního řízeného rehabilitačního programu. Je třeba dbát zvýšeného důrazu na informování a edukaci nemocných s ICHS ve smyslu zintenzívnění jejich pohybového režimu.
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12. Myers J, Ahnve S, Froelicher V et al. A randomized trial of the effects of 1 year of exercise training on computer-measured ST segment displacement in patients with coronary artery disease. J Am Coll Cardiol 1984; 4(6): 1094-1102.
13. Niebauer J, Hambrecht R, Velich T et al. Attenuated progression of coronary artery disease after 6 years of multifactorial risk intervention. Role of physical exercise. Circulation 1997; 96 (8): 2534-2541.
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18. Senti S, Fleisch M, Billinger M et al. Long-term physical exercise and quantitavely assessed human coronary collateral circulation. J Am Coll Cardiol 1998; 32: 49-56.
19. Gould KL, Ornish D, Kirkeeide R et al. Improved stenosis geometry by quantitive coronary arteriography after vigorous risk factor modification, J Am Coll Cardiol 1992; 69(10): 845-853.
20. Schuler G, Hambrecht R, Schlierf G et al. Myocardial perfusion and regression of coronary artery disease in patients on a regimen of intensive exercise and low fat diet. J Am Coll Cardiol 1992; 19: 34-42.
21. Rognmo O, Hetland E, Helgerud J et al.: High intensity aerobic interval exercise is superior to moderate intensity exercise for increasing aerobic capacity in patients with coronary artery disease. Eur J Cardiovasc Prevention and Rehabilitation 2004; 11: 216-222.
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22. European Heart Failure Training Group: Experience from controlled trials of physical training in chronic heart failure. Eur Heart J 1998; 19: 466-475.
23. Benzer W, Platter M, Oldridge NB, et al. Short-term patient-reported outcomes after different exercise-based cardiac rehabilitation programmes. Eur J Cardiovasc Prev Rehabil2007; 14(3): 441-447.
24. Adachi K, Koike A, Obayashi T et al. Does appropriate endurance exercise training improve cardiac function in patients with prior myocardial infarction? Eur Heart J 1996; 17:1511-1521.
25. Swain DP, Franklin BA. Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise. Am J Cardiol. 2006; 97:141-147.
26. Shiroma EJ, Sesso HD, Moorthy MV, et al. Do moderate-intensity and vigorous-intensity physical activities reduce mortality rates to the same extent? J Am Heart Assoc. 2014; 3:e000802.
27. Haskell WL, Alderman EL, Fair JM et al. Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease: the Stanford Coronary Risk Intervention Project (SCRIP). Circulation 1994; 89: 975-990.
28. Frederix I, Driessche NV, Hansen D, et al. Increasing the medium-term clinical benefits of hospital-based cardiac rehabilitation by physical activity telemonitoring in coronary artery disease patients. Eur J Prev Cardiol 2013 [Epub ahead of print].
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31. Focht BC, Brawley LR, Rejeski WJ, Ambrosius WT. Group-mediated activity counseling and traditional exercise therapy programs: Effects on health-related quality of life among older adults in cardiac rehabilitation. Ann Behav Med 2004; 28(1): 52-61.
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32. Schuler G, Schlierf G, Wirth A et al. Low-fat diet and regular, supervised physical exercise in patients with symptomatic coronary artery disease: reduction of stress-induced myocardial ischemia. Circulation 1988; 77(1): 172-181.
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2.2. THE EFFECT OF REGULAR PHYSICAL ACTIVITY ON THE LEFT VENTRICLE SYSTOLIC FUNCTION IN PATIENTS WITH CHRONIC CORONARY ARTERY DISEASE
SUMMARY
Objective: The purpose of this study was to assess the influence of aerobic training on the left ventricular (LV) systolic function.
Methods: Thirty patients with stable coronary artery disease, who had participated in the conducted 3-month physical training, were retrospectively divided into 2 cohorts. While patients in the cohort I (n=14) had continued training individually for 12 months, patients in the cohort II (n=16) had stopped training after finishing the conducted program.
Rest and stress dobutamine/atropine echocardiography was performed in all patients before the training program and 1 year later. The peak systolic velocities of mitral annulus (Sa) were assessed by tissue Doppler imaging for individual LV walls. In addition, to determine global LV systolic longitudinal function, the four-site mean systolic velocity was calculated (Sa glob).
According to the blood supply, left ventricular walls were divided into 5 groups: A- walls supplied by nonstenotic artery; B- walls supplied by coronary artery with stenosis < 50%; C- walls supplied by coronary artery with stenosis 51-70%; D- walls with stenosis of supplying artery 71-99%; and E- walls with totally occluded supplying artery.
Results: In global systolic function, the follow-up values of Sa glob in cohort I were improved by 0.23±0.36 as compared with baseline values at rest, and by 1.26±0.65 cm/s at the maximal load, while the values of Sa glob in cohort II were diminished by 0.53±0.22 (p=NS), and by 1.25±0.45 cm/s (p<0.05), respectively.
Concerning the resting regional function, the only significant difference between cohorts in follow-up changes was found in walls E: 0.37±0.60 versus -1.76±0.40 cm/s (p<0.05). At the maximal load, the significant difference was found only in walls A (0.16±0.84 versus -2.67±0.87 cm/s; p <0.05).
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Conclusion: Patients with regular 12-month physical activity improved their global left ventricle systolic function mainly due to improvement of contractility in walls supplied by a totally occluded coronary artery.
Key words: coronary artery disease - aerobic training - left ventricle systolic function
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ABBREVIATIONS
ACE - angiotensin-converting enzyme
CR - cardiac rehabilitation
EF - ejection fraction
DM - diabetes mellitus
LV - left ventricle
MI - myocardial infarction
TDI - tissue Doppler imaging
2D - two-dimensional
Sa - peak systolic velocity of myocardium adjacent to the mitral annulus
Sa- peak velocity of myocardium adjacent to the mitral annulus during isovolumic contraction
Ea - peak velocity of myocardium adjacent to the mitral annulus during early diastolic phase
Aa - peak velocity of myocardium adjacent to the mitral annulus during atrial contraction
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INTRODUCTION
Beneficial effects of cardiac rehabilitation (CR) on secondary prevention of patients with coronary artery disease are now well-established. The major objective benefits are an increased exercise capacity (Hambrecht et al. 2000) and reduced rates of cardiac events and mortality (Oldridge et al.1988, Hadkell et al.1994). In addition, beneficial effects on coronary risk factors - blood pressure, lipid levels, glucose metabolism, body weight, as well as on the endothelial function and psychological well-being were proved (Shephard and Balady 1999).
On the other hand, only limited data exists concerning the effect of CR on left ventricular (LV) function. Some authors suggest improvements in cardiac function (Klecha et al. 2007, Hambrecht et al. 2000, Belardinelli et al.1996, Giannuzzi et al.1997), whereas others have not found any significant differences between exercise training groups and controls (Dubach et al.1997, Giannuzzi et al.2003). The different results may be due to differences in intensity and duration of training, measurement techniques or patient populations. However, in majority of the studies, LV function has been evaluated by LV ejection fraction (EF) measurements. It is well known that LVEF quantification using standard two-dimensional (2D) echocardiography is strongly dependent on image quality and endocardial border delineation.
Tissue Doppler imaging (TDI) is an echocardiographic technique employing the Doppler principle to measure the velocity of myocardium. Using the pulsed TDI we get the characteristic curve, which consists of three main waves (Figure 1). The positive Sa wave represents a systolic phase of cardiac cycle. This wave is frequently two-phased with the first slim peak of isovolumic contraction (Sa) and second wider wave of ejection of LV. The first negative wave after the Sa wave is called Ea, it represents fast filling of the ventricle in diastolic phase of cardiac cycle. The second negative wave (Aa) grows from atrium contraction at the end of the diastolic phase of cardiac cycle. Pulsed-TDI permits quantification of regional longitudinal myocardial velocities with high temporal resolution and is feasible even in poor acoustic windows. Hence, TDI offered a potentially more accurate quantitative assessment of both regional and global LV function including even more minor changes in systolic LV function that are not detectable during 2D echocardiographic evaluation of LVEF.
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The purpose of this study was to assess the influence of aerobic training on the LV systolic function using TDI measurements.
Figure 1. Characteristic curve of pulse TDI
Sa - peak systolic velocity of myocardium adjacent to the mitral annulus
Sa'- peak velocity of myocardium adjacent to the mitral annulus during isovolumic contraction
Ea - peak velocity of myocardium adjacent to the mitral annulus during early diastolic phase
Aa - peak velocity of myocardium adjacent to the mitral annulus during atrial contraction
PATIENTS AND METHODS
Patient population and study protocol
The study comprised 30 patients with stable coronary artery disease (proved by the coronary angiography performed before the study). All of them had participated in the conducted 3-month physical CR training. The continuation of physical training was recommended to all patients. After 1 year period, these patients were retrospectively
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divided into 2 cohorts. While patients in the cohort I (n=14) had continued training individually for 12 months, patients in the cohort II (n=16) had stopped training after finishing the conducted CR program.
Rest and stress dobutamine/atropine echocardiography was performed in all patients before the training program and 1 year later. For the evaluation of regional systolic LV function, the pulsed TDI was used.
According to the blood supply, LV walls were divided into 5 groups: A- walls supplied by nonstenotic artery; B- walls supplied by coronary artery with stenosis < 50%; C- walls supplied by artery with stenosis 51-70%; D- walls with stenosis of supplying coronary artery 71-99%; and E- walls with totally occluded supplying artery.
The study was in accordance with the Declaration of Helsinki (2000) of the World Medical Association, was approved by the institutional ethics committee and written consent was obtained from each patient.
Physical training
All patients had participated in the conducted outpatient CR. The program offered 3 months of 3 times per week sessions. Each session lasted for 60 minutes and consisted of 3 different phases: 10 minutes warm-up, period of aerobic exercise on bicycle ergometer with load intensity at the level of anaerobic threshold (20 minutes), period of resistance training performed on combined training machine (20 min), and relaxation period (10 min). Aerobic exercise intensity was individually prescribed according to symptom-limited spiroergometry (Blood Gas Analyser, MedGraphics, USA) that was provided before training period for the evaluation of anaerobic threshold.
The 9-months individual training of cohort I consisted of regular physical activity performed for a minimum of one hour at least three times a week. As a regular physical activity the patients have been asked to choose either cycling, riding a velo-ergometer or swimming.
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Echocardiography
Using commercially available equipment Philips Sonos 5500 (Andover, USA) with a 2.5MHz transducer, echocardiographic examinations were performed in one centre by one experienced echocardiographer. 2D images of standard views and pulsed TDI of apical 4- and 2-chamber views were acquired and recorded on videotape for off-line analyses. The peak systolic velocities of myocardium adjacent to the mitral annulus (Sa) were assessed by TDI for individual LV walls: septum, lateral, anterior, and inferior walls. In addition, to determine global LV systolic longitudinal function, the four-site mean systolic velocity was calculated (Sa glob). Velocities were evaluated at rest and at the maximal load.
Dobutamine echocardiography was performed in all patients. Dobutamine was infused with mechanical pump, starting at a dose of 5 ug/kg/min. At 3-minute intervals, the dose was increased incrementally to 10, 20, 30, 40 ug/kg/min until a maximal dose was reached or target heart rate was attained. Intravenous atropine was given in one bolus dose of 0.5mg if the target heart rate was not reached. After the test has been terminated, patients were monitored until baseline condition returned.
Statistical analysis
The changes of global and regional systolic function of individual LV wall groups were compared between cohorts at rest and at the maximal load. To assess normal distribution of variables, the Kolmogorov-Smirnov test was used. An unpaired t-test and Mann-Whitney U test were applied to compare the values of parameters between cohorts; p<0.05 was considered statistically significant.
RESULTS
Baseline characteristics and coronary angiography findings of patients are shown at Table 1 and 2. The majority of parameters have been similar in the two groups - just differences between the number of men and women and the difference between patients
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age in both cohorts have been found. No serious adverse events were found in either group during the follow-up.
Table 1. Characteristics of the study population
Parameter	Cohort I	(n = 14)	Cohort II (n = 16)	
Age (years)	60	(10)	69*	(8)
Men	13	(93 %)	8*	(50 %)
Diabetes mellitus	4	(29 %)	5	(31 %)
Hypertension	14	(100 %)	16	(100 %)
Hyperlipidemia	14	(100 %)	15	(94 %)
Previous myocardial infarction	10	(71%)	9	(57%)
LV EF (%)	50.4	(2.9)	47.9	(2.7)
No of stenotic arteries (>70%)	2.1	(0.2)	1.6	(0.2)
Medication				
Aspirin	14	(100 %)	15	(94 %)
Beta blocker	14	(100 %)	16	(100 %)
ACE inhibitor	10	(71 %)	11	(70 %)
Statin	13	(93 %)	16	(100 %)
Diuretics	4	(29 %)	5	(31 %)
Nitrates	8	(57 %)	11	(69%)
The values are expressed as the mean supplied by standard error (in parentheses) or number (%) of subjects.
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LV = left ventricle; EF = ejection fraction; No = number; ACE = angiotensin-converting enzyme; * p< 0.05 between cohorts
Table 2. Coronary angiography finding in cohorts
Cohort	I (n = 14)			II (n= 16)		
	LAD	LCX	RCA	LAD	LCX	RCA
no stenosis	3 (21%)	2 (14%)	3 (21%)	3 (19%)	6 (38%)	5 (31%)
stenosis < 50	4 (29%)	7 (50%)	0 (0%)	2(13%)	4 (25%)	4 (25%)
stenosis 51-70%	2 (14%)	2 (14%)	3 (21%)	1 (6%)	1 (6%)	2(13%)
stenosis 71-99%	3 (21%)	1 (7%)	3 (21%)	4 (25%)	3 (19%)	2(13%)
totally occluded	2 (14%)	2 (14%)	5 (36%)	6 (38%)	2(13%)	3 (19%)
The values are expressed as number of arteries (%)
LAD = left anterior descending artery; LCX = left circumflex; RCA = right coronary artery
The changes of Sa value after follow-up in different groups of LV walls are shown in Table 3. In global systolic function, the values of Sa glob in cohort I were improved by 0.23±0.36 as compared with baseline values at rest, and by 1.26±0.65 cm/s at the maximal load, while the values of Sa glob in cohort II were diminished by 0.53±0.22 (p=NS), and by 1.25±0.45 cm/s (p<0.05), respectively.
Concerning the resting regional function, the only significant difference between
cohorts in follow-up changes was found in walls E: 0.37±0.60 versus -1.76±0.40 cm/s
(p<0.05). At the maximal load, the significant difference was found only in walls A
(0.16±0.84 versus -2.67±0.87 cm/s; p <0.05). Sa changes in other walls was not significant.
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Table 3. Changes of Sa value after follow-up in different groups of LV walls at rest and at the maximal load
	At rest		At the maximal load	
Cohort	I (n = 14)	II (n = 16)	I (n = 14)	II (n = 16)
Wall group A	-1.56±0.93	-0.86±0.38	0.16±0.84	-2.67i0.87*
B	1.29±0.63	0.62±0.58	3.83Ü.13	0.56Ü.05
C	-0.64±0.69	0.14±0.88	-0.42il.02	-0.58+1.92
D	-0.09±0.86	-0.10±0.30	-2.82il.19	-2.29i0.86
E	0.37±0.60	-1.76±0.40*	1.70Ü.43	0.02i0.78
All (global function)	0.23±0.36	-0.53±0.22	1.26i0.65	-1.25i0.45*
The values are expressed as the mean supplied by standard error (in parentheses)
Sa = peak systolic velocity of mitral annulus; LV = left ventricle;
Wall groups : A- walls supplied by nonstenotic artery; B- walls supplied by artery with coronary stenosis < 50%; C- walls supplied by artery with stenosis 51-70%; D- walls with stenosis of supplying artery 71-99%; and E- walls with totally occluded supplying artery.
* p< 0.05 between cohorts.
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DISCUSSION
Effect of CR on global LV systolic function
The present investigation suggests that long-term exercise training can improve LV systolic function in patients with coronary artery disease. Previous works have shown variable results in relation to influence of CR on the LV function (Klecha et al.2007, Hambrecht et al.2000, Belardinelli et al.1996, Giannuzzi et al.2003). The failure to assess changes in LVEF in some studies may have several reasons. It may be the result of different study populations, kind and intensity of the training programs or the measurement techniques (Webb-Peploe et al.2000). Only patients with chronic heart failure or after myocardial infarction with moderate-to-severe LV dysfunction were included in the majority of studies assessing the influence of CR on LV function. In comparison with them, our patients had only slight depression of LVEF and not all of them underwent clinical myocardial infarction.
The intensity and duration of CR necessary for LV function improvement have not yet been sufficiently evaluated. In the analysis in the work of Piepoli (Piepoli 2004) the data suggested that only long-term duration over 28 weeks of CR may be required to reach benefits in mortality and adverse events rates. The antiremodelling effect of training with a trend towards improvement of LV functional parameters was found after 6-month training in the work of Klecha et al (Klecha et al.2007). On the other hand, the work of Hambrecht (Hambrecht 2000) demonstrated that an intense CR program can improve resting LVEF in 2 weeks. In our work, just 1-year CR improved LV systolic function, while the 3-month training did not provide the sustained long-term functional improvement.
The utilization of LVEF, as an evaluated parameter of LV function, could be one of the main factor contributing to the failure of some previous studies to shown the effect of CR. LVEF is a load-dependent parameter and is very rough to assess expected slight changes of LV function. EF evaluated by 2D echocardiography is strongly dependent on image quality and endocardial border delineation. In contrast, TDI is robust, reproducible and may be more sensitive marker of LV longitudinal systolic function and it is feasible
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even in poor echocardiographic windows. Hence, TDI allows evaluation of even minor changes in LV function that are not detectable by 2D assessment. In several published data, TDI has been applied to stress echocardiography in order to overcome the limitation of only visual analysis (Cain et al.2001, Fathi et al.2001, Bougault et al.2008, Duzenli et al.2008, Garcia et al.2006).
Effect of CR on regional LV systolic function
This present study is the first trial to evaluate the effect of CR on regional LV systolic function in relation to blood supply of individual LV walls. TDI was chosen for this purpose, because it permits quantification of regional longitudinal myocardial systolic velocities with a high temporal resolution and can overcome the limitation in the subjective echocardiographic evaluation of regional ventricular function (Reuss et al.2005).Our data showed that the effect of CR on LV systolic function is caused mainly through the improvement of contractility in walls supplied by a totally occluded coronary artery. The effect of physical training and LV global and regional function was assessed by TDI also in the study of Deljanin-Ilic and al (Deljanin-Ilic et al.2007). After 6 months, LV EF increased significantly as well as the regional systolic myocardial function at the previously infarcted wall only in the training group.
Mechanisms of this training effect have not yet been established. The most likely explanation is the combination of beneficial changes in ventricular wall tension and favorable adaptation in the coronary circulation. The physical training may have beneficial effect on changes in autonomic balance toward a vagal predominance, which could limit the deleterious effects of sympathetic hyperactivity on the LV remodeling and function, analogously to treatment with beta blockers.
In patients with stable coronary artery disease, augmented delivery of blood to ischemic myocardium has been shown to take place in response to physical training (Hambrecht 2004). The beneficial effect of CR on morbidity and mortality has been attributed to the growth of collateral vessels between healthy and underperfused myocardial regions (Shephard and Balady 1999). This theory was documented for example by work of Zbinden et al where beneficial dose-response effect of 3-month endurance
44
exercise training on collaterals has been found (Zbinden et al.2007). However, other human studies have failed to document consistently the formation of collaterals. The main reason for different results may have been the lack of sensitivity of angiography to detect small coronary collaterals. The collateral growth and other coronary vascular changes may improve function of chronically hypoperfused myocardium.
Furthermore, CR has been shown to favourably affect blood flow rheology, thereby possible improving of myocardial perfusion. The improvement in myocardial blood flow to the infarcted area may lead to recovery of both global and regional LV function (Schuler et al.1992).
Although our study cannot elucidate the possible mechanism of regional functional improvement, we speculate, that combination of autonomic system changes and especially the development of collaterals may have facilitated partial functional recovery of dysfunctional but viable myocardial regions supplied by a totally occluded coronary artery.
Study limitations
Our study had several limitations. The study was retrospective, not randomized. The interpretations of results could be limited by a relatively small sample size in both cohorts. Also our study can be influenced by the difference between the number of men and women and the difference between patients age in both cohorts, because age and gender are determining factors for training effects - smaller improvements of women as well as a negative relation between age and improvement in exercise performance is known (Vanhees et al.2004).
Another limitation is the fact, that the 9-months training of cohort II have been performed as an outpatient individual training without any supervision. The information about frequency and intensity has been obtained only from patient's anamnesis during their regular visits in outpatient department. However, very different types of training programmes are described in literature and in some studies, a home-based CR had no significant differences in the main outcomes compared with the centre-based programme (Jolly et al.2009) or an outpatient CR led to further improvement of followed parameters in comparison to supervised CR in a hospital (Benzer et al.2007).
45
Certainly, further research is required, especially in order to optimize the effectiveness of CR programs and to better understand the mechanisms responsible for the improvements related to CR training.
CONCLUSION
In our study, patients with regular 12-month physical activity improved their global left ventricle systolic function mainly due to improvement of contractility in walls supplied by a totally occluded coronary artery.
46
REFERENCES
1. BELARDINELLIR, GEORGIOU D, CIANCI G, PURCARO A: Effects of exercise training on left ventricular filling at rest and during exercise in patients with ischemic cardiomyopathy and severe left ventricular systolic dysfunction. Am Heart J 132: 61-70, 1996.
2. BENZER W, PLATTER M, OLDRIDGE NB, SCHWANN H, MACHREICH K, KULLICH W, MAYR K, PHILIPPI A, GASSNER A, DÖRLER J, HÖFER S: Short-term patient-reported outcomes after different exercise-based cardiac rehabilitation programmes. Eur J Cardiovasc Prev Rehabil 14 (3): 441-447, 2007.
3. BOUGAULT V, NOTTIN S, DOUCENDE G, OBERT P: Tissue Doppler imaging reproducibility during exercise. Int J Sports Med 29 (5):395-400, 2008.
4. CAIN P, MARWICK TH, CASE C, BAGLIN T, DART J, SHORT L, OLSTAD B: Assessment of regional long-axis function during dobutamine echocardiography. Clin Sei 100 (4): 423-432, 2001.
5. DELJANIN-ILIC M, ILIC S, STOICKOV V: Effects of continuous physical training on exercise tolerance and left ventricular myocardial function in patients with heart failure. Srp Arh Celok Lek 135 (9-10): 516-520, 2007.
6. DUBACH P, MYERS J, DZIEKAN G, GOEBBELS U, REINHART W, VOGT P, RATTIR, MULLER P, MIETTUNEN R, BUSER P: Effect of exercise training on myocardial remodeling in patients with reduced left ventricular function after myocardial infarction. Circulation 95:2060-2067, 1997.
7. DUZENLI MA, ÖZDEMIR K, AYGUL N, ALTUNKESER BB, ZENGIN K, SIZER M: Relationship between systolic myocardial velocity obtained by tissue doppler imaging and left ventricular ejection fraction: Systolic myocardial velocity predicts the degree of left ventricular dysfunction in heart failure. Echocardiography 25(8): 856-863, 2008.
8. FATHI R, CAIN P, NAKATANI S, YU HC, MARWICK TH: Effect of tissue Doppler on the accuracy of novice and expert interpreters of dobutamine echocardiography. Am J Cardiol 88 (4): 400-405, 2001.
9. GARCIA EH, PERNA ER, FARIAS EF, OBREGON RO, MACIN SM, PARRAS JL AGUERO MA, MORATORIO DA, PITZUS AE, TASSANO EA, RODRIGUEZ L: Reduced systolic performance by tissue Doppler in patients with preserved and abnormal ejection fraction: New insights in chronic heart failure. Int J Cardiol 108 (2): 181-188, 2006.
10. GIANNUZZIP, TEMPORELLI PL, CORRA U, GATTONE M, GIORDANO A, TAVAZZIL: Attenuation of unfavourable remodeling by exercise training in postinfarction patients with left ventricular dysfunction (ELVD) trial. Circulation 96:1790-1797, 1997.
11. GIANNUZZI P, TEMPORELLI PL, CORRA U, TAVAZZI L: Antiremodeling effect of long-term exercise training in patients with stable chronic heart failure. Results of the Exercise in Left Ventricular Dysfunction and Chronic Heart Failure (ELVD-CHF) Trial. Circulation 108: 554-559, 2003.
12. HAMBRECHT R, GIELEN S, LINKE A, FIEHN E, YU J, WALTHER C, SCHOENE N, SCHULER G: Effects of exercise training on the left ventricular function and peripheral resistance in patients with chronic heart failure. A randomized trial. JAMA 283: 3095-3101, 2000.
13. HAMBRECHT R, WALTHER C, MOEBIUS-WINKLER S, GIELEN S, LINKE A, CONRADI K, ERBS S, KLUGE R, KENDZIORRA K, SABRI O, SICK P, SCHULER G: Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease. A randomized trial. Circulation 109: 1371-1378,2004.
14. HAMBRECHT R, WOLF A, GIELEN S, LINKE A, HOFER J, ERBS S, SCHOENE N, SCHULER G: Effects of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med 342: 454-460, 2000.
15. HASKELL WL, ALDERMAN EL, FAIR JM, MARON DJ, MACKEY SF, SUPERKO R, WILLIAMS PT, JOHNSTONE IM, CHAMPAGNE MA, KRAUSS RM: Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease: the
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Stanford Coronary Risk Intervention Project (SCRIP). Circulation 89: 975-990, 1994.
16. JOLLY K, LIP GYH, TAYLOR RS, RAFTERY J, MANT J, LANE D, GREENFIELD S, STEVENS A. The Birmingham rehabilitation uptake maximisation study (BRUM): a randomised controlled trial comparing home-based with centre-based cardiac rehabilitation. Heart 95: 36-42, 2009.
17. KLECHA A, KAWECKA-JASZCZ K, BACIOR B, KUBINYI A, PASOWICZ M, KLIMECZEK P, BANYS R: Physical training in patients with chronic heart failure of ischemic origin: effect on exercise capacity and left ventricular remodeling. Eur J Cardiovasc Prev Rehabil 14 (1): 85-91, 2007.
18. OLDRIDGE NB, GUYATT GH, FISCHER ME, RIMM AA: Cardiac rehabilitation after myocardial infarction: combined experience of randomized clinical trials. JAMA 260: 950-954, 1988.
19. PIEPOLIMF: Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH). BMJ 328: 189-196, 2004.
20. REUSS CS, MORENO CA, APPLETON CP, LESTER SJ: Doppler tissue imaging during supine and upright exercise in healthy adults. J Am Soc Echocardiogr 18 (12): 1343-1348,2008
21. SCHULER G, HAMBRECHT R, SCHLIERF G, GRUNZE M, METHFESSEL S, HAUER K, KUBLER W: Myocardial perfusion and regression of coronary artery disease in patients on a regimen of intensive exercise and low fat diet. J Am Coll Cardiol 19: 34-42, 1992.
22. SHEPHARD RJ, BALADY GJ: Exercise as cardiovascular therapy. Circulation 99: 963-972, 1999.
23. VANHEES L, STEVENS A, SCHEPERS D, DEFOOR J, RADEMAKERS F, FAGARD R. Determinants of the effects of physical training and of the complications requiring resuscitation during exercise in patients with cardiovascular disease. Eur J Cardiovasc Prev Rehabil 11 (4): 304-312, 2004.
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24. WEBB-PEPLOE KM, CHUA TP, HARRINGTON D, HENEIN MY, GIBSON DG, COATS AJS: Different response of patients with idiopatic and ischaemic dilated cardiomyopathy to exercise training. Int J Cardiol 74 (2-3): 215-224, 2000.
25. ZBINDEN R, ZBINDEN S, MEIER P, HUTTER D, BILLINGER M, WAHL A, SCHMID JP, WINDECKER S, MEIER B, SEILER C: Coronary collateral flow in response to endurance exercise training. Eur J Cardiovasc Prev Rehabil 14 (2): 250-257, 2007.
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2.3. ASSESSING THE LEFT VENTRICLE DIASTOLIC FUNCTION IN A
GROUP OF PATIENTS WITH CHRONIC ISCHAEMIC HEART DISEASE AND REGULAR PHYSICAL ACTIVITY
ABSTRACT
Aim: Assessing the left ventricle diastolic function in a group of patients with stable coronary artery disease and regular physical training.
Methods: The study included thirty patients with stable coronary artery disease. Every patient had participated in the conducted 3-month physical training in Department of Functional Diagnostic and Rehabilitation St. Anna Hospital. After one year patients were retrospectively divided into two cohorts according to their physical activity. The patients in cohort C (consists of 14 patients) continued in aerobic physical training after the end of rehabilitation program. The patients in cohort N (consists of 16 patients) had stopped their training after finishing the conducted program in St. Anna Faculty Hospital.
The peak diastolic velocities of myocardial motion were measured at individual LV walls: septum, lateral, anterior, and inferior walls. In addition, to determine global LV diastolic function, the four-site mean diastolic velocity was calculated (Ea glob, Ea/Aa glob). Velocities were evaluated at rest and at the maximal load.
According to the blood supply, left ventricular walls were divided into five groups: 0- walls supplied by non-stenotic artery; 1- walls supplied by artery with coronary stenosis < 50%; 2- walls supplied by artery with stenosis 51-70%; 3- walls with stenosis of supplying artery 71-99%; 4- walls with totally occluded supplying artery. For every patient the difference between values Ea, Ea/Aa for each wall at the end of the study and the values at the beginning of the study was assessed. The values of particular walls were divided into 5 groups according to the blood supply (this 5 groups were create using coronarography).
The differences of these values at rest and stress between both cohorts of patients were statistically processed using unpaired t-test, the p<0.05 was considered statistically significant.
51
Results: In global diastolic function, the values of Ea global in cohort C were improved by 0.05±2.94 cm/s at rest, and by o 1.27±3.75 cm/s at maximal load, while the values of Ea global in cohort N were diminished by -0.89±2.01 cm/s (p<0.05 versus cohort C), and by -0.13±3.20 cm/s; (p<0.05 versus cohort C) at maximal load.
The most important benefit at diastolic function was found in group 4 (groups with totally occluded coronary artery). The values of Ea in cohort C were improved by 4.24±3.65 cm/s, while the values in cohort N were diminished by -0.68±2.74 cm/s; (p<0.05 versus cohort C) at maximal load. The other Ea values results were not significant.
The Ea/Aa values in group 4 in cohort C were improved by 0.29±0.39 cm/s at maximal load , while values of Ea/Aa in cohort N were diminished by -0.03±0,24 cm/s; (p<0.05 versus cohort C) at maximal load. The other Ea/Aa values results were not significant.
Conclusion: Our patients with 12 months training improved their global diastolic function. The most important benefit was found in walls supplied by occluded artery.
Key words: aerobic training, left ventricle diastolic function, chronic ischemic heart disease
52
INTRODUCTION
The effects of regular physical activity on cardiovascular system and myocardial function are global. The risk factors are reduced (by changing the way of life, strength of thews). Heart rate and blood pressure are decreased, peripheral venous tonus is improved and positive influence on the left ventricle (LV) is probable.
Tissue Doppler imaging (TDI) is echocardiographic method using the Doppler effect. By this method it is possible to measure the velocity of myocardial motion in both systolic and diastolic phases of cardiac cycle [1]. The difference between classic Doppler sonography and TDI is in using special filters, that eliminate signals which are repulsed back by blood cells, and reversible intensify signals that are repulsed by myocardium (these signals are marked with high amplitude and low frequency).
There are two types of TDI: pulsed TDI and colour TDI. Using the pulsed TDI we get the characteristic curve, which consists of three main waves. The positive Sa wave represents a systolic phase of cardiac cycle. This wave is frequently two-phased with the first slim peak of isovolumic contraction (Sa') and second wider wave of ejection of LV. The first negative wave after the Sa wave is called Ea, it represents fast filling of the ventricle in diastolic phase of cardiac cycle. The second negative wave (Aa) grows from atrium contraction at the end of the diastolic phase of cardiac cycle. The Aa wave is missing in the case of atrial fibrillation [2]. During exercise tests the waves Ea and Aa are often fusing [3] cause to the faster heart rate.
By measuring the amplitude of these single waves, the maximal velocity of each myocardial segment during cardiac cycle can be evaluated. In myocardial pathologies velocity values for each segment and also the overall value of ventricle function are being changed. The velocity of all 17 myocardial segments can be measured [4]. Physiologically, the velocities are getting higher in segments from apex towards heart base. TDI can be used for evaluation of regional and also global function of both ventricles (both systolic and diastolic ventricle function). We can prove the myocardial ischaemia, and the reversible and non-reversible myocardial dysfunction [2]. During ischaemia the maximal Sa and Ea velocities are reduced. The change of Aa is not significant, so the Ea/Aa ratio in ischaemic area is getting down [1].
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The purpose of this study was to assess the effect of aerobic training on the left ventricular diastolic function in group of patients with chronic ischemic heart disease.
MATERIALS AND METHODS
The study included thirty patients with stable coronary artery disease. These patients were retrospectively divided into two cohorts with difference in regular physical training. The cohort C consists of 14 patients. These patients had participated in the conducted 3-month physical training in Department of Functional Diagnostic and Rehabilitation St. Anne's Faculty Hospital, and after the 3-months they had continued with individual training for 9 more months. The regular physical training consists of 3 phase in 60 minutes 3 times a week. The first phase of the training is called warming up and lasts for ten minutes. The second phase is an aerobic period and lasts for 35 minutes. This phase consists of power training and riding a bicycle ergometer. The third phase is a relaxation phase and lasts for 15 minutes. The 9-months individual training consists of regular physical activity performed for one hour at least three times a week. As a regular physical activity the patients should have chosen riding a bicycle-ergometer, cycling, or swimming. The cohort N consists of 16 patients. These patients had stopped the training after finishing the conducted program. Cohort's characteristics are shown in Table 1.
Table 1. Study population
	Cohort C	cohort N	
Age (years)	60±10	69±8	
Nu mber of a rteries. wi th stenos i s > 70 %	1.6±1.1	1.8±1.2	
DM	43%	19%	
Ml	50%	63%	
Hypertension	100%	100%	
HLPP	100%	94%	
EF<%)	50.8+10.8	4&6±12.4	
Male/female	13/1	9/7	*
Values are shown as average ± standard deviation;
EF-ejection fraction LV; Ml-myocardial infarction; DM-diabetes mellitus; HLPP-hyperlipoproteinemia; * p<0.05 between cohorts
54
At the beginning of the study the coronary angiography was performed. According to the blood supply, left ventricular walls were divided into five groups: 0- walls supplied by nonstenotic artery; 1- walls supplied by artery with coronary stenosis < 50%; 2- walls supplied by artery with stenosis 51-70%; 3- walls with stenosis of supplying artery 71-99%; 4- walls with totally occluded supplying artery.
Rest and stress dobutamine/atropine echocardiography was performed in all patients before the training program and one year later. Three days before the rest/stress dobutamine echocardiography the beta blockers were discontinued. Using commercially available equipment Sonos 5500 (Hewlet-Pacard, US) with transducer 2.5 MHz, echocardiography was performed in standard views - parasternal long axis, parasternal short axis (level of papillary muscles), apical 4- and 2- chamber views. The peak diastolic velocities of myocardial motion were measured at individual LV walls: septum, lateral, anterior, and inferior walls. In addition, to determine global LV diastolic function, the four-site average diastolic velocity was calculated (Ea glob, Ea/Aa glob). Velocities were evaluated at rest and at the maximal load.
For every patient the difference between values Ea, Ea/Aa for each wall at the end of the study and the values at the beginning of the study was assessed. The values of particular walls were divided into 5 groups according to the blood supply (this 5 groups were create using coronary angiography). The differences of these values during rest and maximal stress between both cohorts of patients were statistically processed using unpaired t-test, a p<0.05 was considered statistically significant.
RESULTS
The results are shown in Table 2.
In global diastolic function, the values of Ea global in cohort C were improved by 0.05±2.94 cm/s at rest, and by o 1.27±3.75 cm/s at maximal load, while the values of Ea global in cohort N were diminished by -0.89±2.01 cm/s (p<0.05 versus cohort C), and by -0.13±3.20 cm/s; (p<0.05 versus cohort C) at maximal load.
The most important benefit to the diastolic function was found in group 4 (groups
with totally occluded coronary artery). The values of Ea in cohort C were improved by
55
4.24±3.65 cm/s, while the values in cohort N were diminished by -0.68±2.74 cm/s; (p<0.05 versus cohort C) at maximal load.
Table 2. Changes of value characteristics of diastolic function
	rest						stress					
	Ea			Ea/Aa			Ea			Ea/Aa		
Cohort	C	N		C	N		C	N		C	N	
0	-0.64+2.08	-l.44il.66		-0,02+0.14	-0,10+0.24		-0.44±2.53	-1,03±2P24		-0.14±0.25	0.04±OJ7	
1	C.27±2,93	-0.26±1.37		-O.O5±0.28	0.03±0,12		1.25±2.78	2.05±337		0,01±0P17	0.11 ±0,20	
2	0.59+2,62	-1.64±3.69		0.13±0.08	-0,11 ±038		0.51 ±2,37	0.62±4,97		O,OO±0.2O	0.13±0,43	
3	0.55+3,68	-Q.66±1.71		0.03±O,34	0.14±0.30		-0.04±4.86	-0.4S±3.00		0.09+Q.57	0.25±0,57	
4	-0.4S±2.77	-Q.77±2.28		-0.06±0.22	Q.Q3±0.18		4.24±3.6S	-0,68±2.74		0,29 ±0.39	-0.03 ±0.2 4	
Global function	0.05±2.94	-0.89±2,01		-0.02+0.26	0.02+J026		1.27+3.75	-0.13±3.20		O.O6+0.36	0.09±O,38	
Values are shown as average ± standard deviation;* p<0.05 between cohorts; rest=investigation in rest; stress= investigation during maximal load; C= cohort C; N= cohort N; group 0,1,2,3,4= according to the blood supply; global function= Ea global or Ea/Aa global as a average of all walls LV
The results of the Ea values from other walls were not significant.
The Ea/Aa values in group 4 in cohort C were improved by 0.29±0.39 cm/s at maximal load, while values of Ea/Aa in cohort N were diminished by -0.03±0.24 cm/s; (p<0.05 versus cohort C) at maximal load. The changes of other Ea/Aa values results were not significant.
In cohort C, as the stress test was performed, 12 of 14 patients have stress-induced kinetic disorder, 2 patients have negative stress test. In cohort N, 12 of 16 patients have stress-induced kinetic disorder (4 patients have negative stress test, but 2 of them have typical stress performed chest pain without objective kinetic disorder).
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DISCUSSION
In our study, using TDI for assessing changes of the diastolic function of LV, the regular physical activity has positive influence on diastolic function of LV. We found the improvement of global diastolic function during the rest and also during the maximal load. The most important benefit was found in walls supplied by occluded artery.
In the literature, there are very few studies using pulsed TDI to evaluate the effect of cardiac rehabilitation on LV function. Moreover, population cohorts are very different. Schuster et al. [5] reported improvement of global diastolic function assessed by TDI in obese men with subclinical cardiac dysfunction after eight weeks of training. In the cohort of patients with chronic kidney disease, Howden et al. [6] found an improvement of diastolic LV function after comprehensive intervention including physical training. Arbab-Zadeh et al [7] has found that prolonged, endurance training preserves ventricular compliance with aging and may help to prevent heart failure in elderly. In patients with coronary artery disease after myocardial infarction, Deljanin - Ilic et al. [8] has reported that continuous physical training induced significant improvement of regional diastolic LV function. In the study of Yu [9], cardiac rehabilitation and prevention program prevented the progression of resting LV diastolic dysfunction, without affecting systolic function. The improvement of diastolic function predicted the gain in exercise capacity.
However, the results of some studies are different. In the study of Nottin et al [10], master athletes with long-term endurance training were compared with sedentary seniors and young adult men. The authors concluded that the endurance training does not prevent the LV diastolic dysfunction. In post myocardial infarction patients, an 8-week cardiac rehabilitation program led to improved exercise capacity. However, it failed to enhance diastolic function [11]. A 4.5-month training program in post-myocardial infarction patients with preserved systolic function and mild diastolic dysfunction did not led to improve diastolic function in the study of Korzeniowska-Kubacka et al. [12].
We have to be cautious in our conclusion of diastolic function improvement, because the age average in both cohorts is not the same. It is known that the diastolic function is getting worse over the age [13], and the patients in cohort N were significantly older than those in cohort C. And there was also a difference between substitution of men and women in both cohorts [14].
57
Although our study cannot elucidate the possible mechanism of regional functional improvement, we speculate, that combination of autonomic system changes and especially the development of collaterals may have facilitated partial functional recovery of dysfunctional but viable myocardial regions supplied by a totally occluded coronary artery. Several studies have shown that exercise training programs augment coronary collateral supply to native vessels. There appears to be a dose-response relation between coronary collateral flow augmentation and exercise capacity gained [15].
Our study has several limitations. The interpretations of results may be limited by a relatively small number of patients in both cohorts. Also, our study can be influenced by the difference between the number of men and women and the difference between patients' age in both cohorts.
CONCLUSION
In our study, patients with regular 12-month physical activity improved their global left ventricle diastolic function mainly due to improvement of regional diastolic function in walls supplied by a totally occluded coronary artery.
58
LITERATURE
[1.]     Petr Niederle a kolektiv: Echokardiografie, l.díl - echokardiografie dospělých, Triton 2000. 70-71 s. ISBN 80-7254-281-8.
[2.]     Nikitin NP, Witte KK.: Application of tissue Doppler imaging in cardiology. [Review] [120 refs] [Journal Article. Review. Review, Academic] Cardiology 2004;101:170-84.
[3.]     Yamada, E., Garcia, M., Thomas, J.D. et al.: Myocardial Doppler velocity imaging - a quantitative technique for interpretation of dobutamine echocardiography. Am J Cardiol 1998;82:806-809.
[4.]     Cerqueira MD, Weissman NJ, Dilsizian V, et al.: Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. J Am Soc Echocardiogr 2002;15:464-8.
[5.]      Schuster I, Vinet A, Karpoff L, et al. Diastolic dysfunction and intraventricular
dyssynchrony are restored by low intensity exercise training in obese men.
Obesity 2012;20(1):134-140. [6.]     Howden EJ, Leano R, Petchey W, et al. Effects of exercise and lifestyle
intervention on cardiovascular function in CKD. Clin J Am Soc Nephrol
2013;8(9):1494-1501.
[7.]     Arbab-Zadeh A, Dijk E, Prasad A, et al.: Effect of aging and physical activity on left ventricular compliance. Circulation 2004;110:1799-1805.
[8.]     Deljanin-Ilic M, Ilic S, Stoickov V. Effects of continuous physical training on exercise tolerance and left ventricular myocardial function in patients with heart failure. Srp Arh Celok Lek 2007; 135(9-10):516-520.
[9.]     Yu CM, Li LS, Lam MF, et al.: Effect of cardiac rehabilitation program on left ventricular diastolic function and its relationship to exercise capacity in patients with coronary heart disease: Experience from a randomized, controlled study. American Heart J 2004;147:e24.
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[10.]    Nottin S, Nguyen LD, Terbah M, Obert P.: Long-term endurance training does not prevent the age-related decrease in the left ventricular relaxation properties. Acta Physiol Scand 2004;181:209-215.
[11.]    Golabchi A, Basati F, Kargarfard M, Sadeghi M. Can cardiac rehabilitation
programs improve functional capacity and left ventricular diastolic function in patients with mechanical reperfusion after ST elevation myocardial infarction?: A double-blind clinical trial. ARYA Atheroscler 20121;8(3):125-129.
[12.]    Korzeniowska-Kubacka I, Bilihska M, Michalak E, et al. Influence of exercise training on left ventricular diastolic function and its relationship to exercise capacity in patients after myocardial infarction. Cardiol J. 2010;17(2):136-142.
[13.]    Pedone MD, Castro I, Hatem D, et al.: Changes in the parameters of left ventricular diastolic function according to age on tissue Doppler imaging. Arquivos Brasileiros de Cardiologia 2004;83:461-469.
[14.] Forman DE, Manning WJ, Hauser R, et al.: Enhanced left ventricular diastolic filling associated with long-term endurance training. J Gerontol 1992;47:M56-M58.
[15.]    Zbinden R, Zbinden S, Meier P, et al. Coronary collateral flow in response to
endurance exercise training. Eur J Cardiovasc Prev Rehabil 2007;14(2):250-257.
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2.4. THE PROGNOSTIC EFFECT OF DIFFERENT TYPES OF CARDIAC REHABILITATION IN PATIENTS WITH CORONARY ARTERY DISEASE
ABSTRACT
Aim: The purpose of this study was to access and compare the prognostic effects of different types of cardiac rehabilitation (CR) in patients with chronic coronary artery disease.
Methods: One hundred fifty two patients were retrospectively divided into 4 groups according to their adherence to physical activity recommendations. Patients in groups 1 and 2 participated in the guided 3-month exercise program. Patients in group 1 then continued with individual exercise training, while patients in the group 2 stopped exercising after finishing the guide exercise program. Patients in group 3 participated only in individual exercise training throughout the whole follow-up period, and patients in group 4 declined all exercise recommendations and did not exercise. The prognostic outcome of different types of cardiac rehabilitation was compared among groups. In addition, patients who participated in individual exercise training according to recommendations (cohort IT+) were compared with patients who declined these activities (cohort IT-).
Results: During a median follow-up of 94 months, 33 deaths occurred: 17 cardiovascular and 16 non-cardiac deaths. A Kaplan-Meier survival analysis demonstrated significantly better survival rates for patients who followed a long-term aerobic exercise training (IT+) than for those who did not participate or who had only a short-term exercise programs (IT-) (p=0.009).
Conclusion: In our study, long-term exercise training had a higher impact on patient survival than short-term guided CR.
Key words: coronary artery disease, cardiac rehabilitation, prognosis, cardiovascular risk
61
INTRODUCTION
The beneficial effects of cardiac rehabilitation (CR) on secondary prevention of coronary artery disease are well-established and regular physical activity, including
1-3
exercise, is recommended by many guidelines " . The major objective benefits are an increased exercise capacity 4 and reduced rates of cardiac events and mortality 5. In addition, the beneficial effects on cardiovascular risk factors - blood pressure, lipid levels, glucose metabolism, body weight, as well as on the endothelial function and psychological well-being - have also been proven 6.
The structure and intensity of CR programs varies widely among different countries and centers . However, in spite of their benefits and guideline recommendations, only a minority of eligible patients participated in and completed these programs. Alternative home-based CR activities might help to solve the problems of the poor uptake and adherence of outpatients or inpatients to center-based CR programs. Furthermore, the physical activity behaviors of patients, especially their participation in walking and vigorous activities, were found to be inversely associated with the use of antidiabetic,
8 9
antihypertensive, and lipid-lowering drugs ' .
The purpose of this study was to assess and compare the prognostic effects of different types of aerobic exercise programs in patients with chronic stable coronary artery disease.
PATIENTS AND METHODS
Patient population and study protocol
The study comprised 152 consecutive patients with stable coronary artery disease with at least one coronary artery stenosis more than 50% in luminal diameter (proved by the coronary angiography performed before the study). The exclusion criteria were: 1. coronary artery bypass graft or coronary intervention less than 3 months before inclusion; 2. known need for future coronary revascularization; 3. unstable patients; 4. hemodynamically important valve disease; 5. non-cardiac disease adversely affecting
62
prognosis; and 6. non-cardiac disease seriously limiting the participation in cardiac exercise programs.
Participation in the supervised outpatient cardiac rehabilitation and individual aerobic exercise training programs were recommended to all patients. After the follow-up, the patients were retrospectively divided into 4 groups according to their acceptance of the exercise recommendation. Patients in groups 1 and 2 participated in the guided 3-month physical exercise program. Patients in group 1 continued to exercise individually; patients in the group 2 stopped their exercise after finishing the guided program. Patients in group 3 participated only in an individual exercise training program throughout the follow-up period, and patients in group 4 declined all exercise recommendations and did not exercise. For further evaluation of the effect of different types of aerobic exercise, patients who attended the supervised cardiac rehabilitation (cohort CR+, comprising patients of groups 1 and 2) were compared with patients who did not (cohort CR-, comprising patients of groups 3 and 4). Similarly, patients who participated in individual training program in accordance with the recommendation (cohort IT+, comprising patients of groups 1 and 3) were compared with patients who declined these activities (cohort IT-, comprising patients of groups 2 and 4).
During follow-up period, all patients were medically treated according to the evidence-based medicine. Significant effort was spent also on motivating the patients toward nonpharmacological treatment of risk factors, including not only physical exercise, but also smoking cessation, dietary and weight recommendations. Mortality and major adverse cardiac events (MACE) were assessed during follow-up visits. The primary end-point was all-cause mortality; the secondary end-points were a composite of MACE, including myocardial infarction, unstable angina pectoris, coronary revascularization, and hospitalization for heart failure.
The study was in accordance with the Declaration of Helsinki (2000) of the World Medical Association, and was approved by the institutional ethics committee. Written consent was obtained from each patient.
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Physical exercise
The guided program offered 3 months of 3 times weekly sessions. Each session lasted for 60 minutes and consisted of 3 different phases: 10 minutes of warm-up, 20 minutes of aerobic exercise on a bicycle ergometer with a load intensity at the level of anaerobic threshold, 20 minutes of resistance training on combined training machine, and 10 minutes of relaxation.
Aerobic exercise intensity was individually prescribed according to initially performed symptom-limited spiroergometry. The protocol with intensified workload up to the symptom- limited maximum was used starting on 40W, increasing by 20W each 2 minutes. The respiratory gases were analyzed under physical exercise (Blood Gas Analyser, MedGraphics, USA). The anaerobic threshold value for prescribing suitable load intensity was determined according to the corresponding value of heart rate and degrees of the Borg scale of subjective perception of load intensity.
The individual exercise training program consisted of regular physical activity performed for a minimum of 1 hour at least 3 times per week. As a regular physical activity, patients were asked to choose cycling, riding a veloergometer or swimming.
Statistical analysis
For descriptive purposes, basic summary statistics such as mean, median, standard deviation, minimum and maximum were assessed for continuous data analysis, and absolute and relative frequencies for binary and categorical data. Groups were compared in continuous parameters by ANOVA or Kruskal-Wallis AN OVA test if appropriate (the Kolmogorov-Smirnov test was used to analyze distribution of data). Distribution of binary and categorical data between groups was tested by a chi-square test.
Survival analysis (overall survival and cardiovascular survival) was performed using the Kaplan-Meier method, and groups were compared by log-rank test or by chi-square test. Cox proportional hazard regression model was used for multivariate analysis. All data were analyzed at the significance level of a=0.05, and all the tests were two-tailed.
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RESULTS
Baseline patient characteristics are presented in Tables 1 and 2. Most parameters were similar in all four groups, but there were significant differences among the groups in age, sex, and in the number of diabetic and dyslipidemic patients. Medical treatment before the study and after follow-up is shown in Tables 3 and 4. No statistically significant differences were found among the 4 groups.
During a median follow-up of 94 months (range 2-158) after inclusion, there were 33 deaths (17 cardiovascular and 16 non-cardiac deaths). The Kaplan-Meier survival curve for all four groups is shown in Figure 1. Patients in group 3 had statistically better survival than group 2 (p=0.042) and group 4 (p=0.041). The survival between other groups did not differ statistically. The result of an overall test comparing all patient groups bordered on statistical significance (p=0.067). No significant differences in survival were found between cohorts CR+ and CR- (p=0.948). However, patients in cohort IT+ had longer survival rates than cohort IT- (p=0.009) (Figure 2). Multivariate Cox regression analysis including baseline covariates (sex, age, diabetes mellitus, and dyslipidemia) revealed group as an independent factor for survival on the borderline of statistical significance (p=0.057).
The secondary end-points are shown in Table 5. The incidence of each of unstable angina pectoris, coronary revascularization, and hospitalization for heart failure significantly differs among the groups and was higher in cohort IT- than cohort IT+. The composite secondary end-point differed significantly among groups and between cohorts IT+ and IT-, but no difference was found between cohorts CR+ and CR-.
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Table 1. Study groups characteristics: medical history (groups 1-4)
1 Parameter	Group 1	Group 1	Group J	Group 4	Pvalue
	(n = 32)	{n = *0)	{■1 = 22}	(n = 38)	
Age {years)	71,5 ±10.0	71.8 ±8,8	63.8 ±10.3	73.9 ± 8.7	0,002*
Men	32 (100.0%)	43(71.7%)	20(90.9%)	27(71.0%)	< 0.001*
BMI	27.3 ±13	28.3 ±3.0	28.3 ±3.0	27.6 ± 3.8	0.622
LVEF (%)	48,6 ±6.8	46.9 ±10,1	49.5 ±7,6	50.1+11.6	0,276
No of stenotic arteries 70%)	1.5 ±0.7	1.5 ±0.7	1.4 ±0.6	1.4 + 0.6	0.526
Coro na ry revascu larization	19(59.4%)	20(48.3%)	15(682%)	17(44.7%)	0.243
DM	5 (15.6%)	10(31.7%)	2(9.1%)	14(36.8%)	0.028*
Hypertension	31 (96.9%)	58 (06.7%)	22 (100.0%)	37(97.4%)	0.727
Dyslipidaemia	25 (78.1%)	53 [88.3%)	22(100.0%)	38(100.0%)	< 0.001*
Smoking	8 (25.0%)	8(13.3%)	7(31.8%)	6(15.8%)	0.223
Values are expressed as the mean ± standard deviation or the number of subjects with the percentage in parentheses.
BMI = body mass index; LV EF = left ventricular ejection fraction; DM = diabetes mellitus; * p< 0.05 between groups.
Table 2. Study cohort characteristics: medical history (groups CR+, CR-, IT+, IT-)
Parameter	Group CB+ (n = 92)	Group CR-(n=M»	Pvalue	Group IT+ (■=»»	Group IT-(n = 98(	P value
Age (years)	71.7 ±9.1	70.2 ± 10.4	0.302	68.4 ±10.7	72.6 ±8.7	0.007*
Men	75(81.5%)	47(78.3%)	0.679	52(96.3%)	70 (71.4%)	< 0.001*
BMI	27.0 ±3.2	27.0 ±3.5	0.867	27.7 ±3.2	28.0 ±3.3	0.585
LVEF (%)	47.5 ±9.7	49.9 ±10.2	0.091	48.0 ±8.3	48.1 ± 10.8	Oil 9
No of stenotic arteries 70%)	1.5 ±0.7	1.4 ±0.6	0.148	1.4 ±0.7	1.5 ±0.7	0.868
Coro na ry revascu larization	48(522%)	32(533%)	0.909	34(63.0%)	46 (47.0%)	0.064
DM	24(26.1%)	16(26.7%)	0.909	7(13.0%)	33 (33.7%)	0.007*
Hypertension	89(96.7%)	59(98.3%)	0.909	53(98.1%)	95(969%)	0.999
Dyslipidaemia	78(84.8%)	60(100.0%)	< 0.001*	47(87.0%)	91 (92.6%)	0253
Smoking	16(17.4%)	13(21.7%)	0532	15(27.8%)	14(14.3%)	0.053
Values are expressed as the mean ± standard deviation or the number of subjects with the percentage in parentheses.
CR+ = patients who participated in the guided exercise program (comprising patients of groups 1 and 2); CR- = patients who declined to participate in the guided exercise program (comprising patients of groups 3 and 4); IT+ = patients who exercised individually training (comprising patients of groups 1 and 3); IT- = patients who declined individual exercise (comprising patients of groups 2 and 4); BMI = body mass index; LV EF = left ventricular ejection fraction; DM = diabetes mellitus; * p< 0.05 between cohorts
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Table 3. Study population characteristics: medical treatment before the study
1 Parameter	Group 1	Group 2	Group}	Group 4	P value 1
	<n = H)	{n = 60)	(n=M)	(n = M(	
ASA	31 [96.9%)	57(95.0«}	20(90.9%)	35 (92.1%)	0.748
Beta-blockers	29 (90.6%)	58 [96.7%)	22(100.0%)	35 (92.1%)	0.236
ACEI	28 [87.5%)	50(83.3%)	21 (95.5%)	28 (73.7%)	0.123
Saltans	0 (0.0%)	1 [1.7%)	1 (4.6%)	0 (0.0%)	0.393
Statins	23 (71.9%)	49(81.7%)	19(86.4%)	35(92.1%)	0.146
Nitrates	24(75.0%)	41 (68.3%)	13(59.1%)	29 (763%)	0.495
Values are expressed as the number of subjects with the percentage in parentheses. ASA = acetylsalicylic acid; ACEI = angiotensin-converting-enzyme inhibitor
Table 4. Study population characteristics: medical treatment at the end of the follow up
1 Parameter	Group 1	Group 2	Group 3	Group 4	fvalue
	(»=»)	(n = 60)	<n = 2I)	(n = 3*>	
ASA	31 (96.9%)	58(96.7%)	20 (90.9%)	36(94.7%)	0.740
Beta-blockers	30(93.8%)	58(96.7%)	22(100.0%)	35 (92.1%)	0.351
ACEI	21 (65j6%)	45(75.0%)	19 (86.4%)	25 (65.8%)	0.243
Sartaris	2 (6.3%)	8(13.3%)	4(182%)	5(132%)	0.572
Statins	28(87.5%)	54(90.0%)	20 (90.9%)	35 (92.1%)	0.935
Mitrates	18(56.3%)	39(65.0%)	13(59,1%)	30(79.0%)	0.182
Values are expressed as the number of subjects with the percentage in parentheses. ASA = acetylsalicylic acid; ACEI = angiotensin-converting-enzyme inhibitors.
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Figure 1. Kaplan-Meier curve for patient survival according to the physical activity - a comparison of 4 groups of patients
N=152; p=0.067
Group 3 Group 1
■j—: Group 4
Group 2
0.0   '-'-1-'-'-'-'-1-'-'-'
0       20       40       60       80      100     120     140     160     180 200
Time [months]
Group 1 = patients participated in the supervised 3-month physical exercise program and continued to exercise individually; Group 2 = patients participated in the supervised 3-month physical training and stopped exercise after that; Group 3 = patients only exercised individually throughout the whole follow-up period; Group 4 = patients declined all exercise recommendations and did not perform any exercise activities.
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Figure 2. Kaplan-Meier curve for patient survival according to the physical activity - a comparison of cohorts IT+ and IT-.
N=152;p=0.009
Cohort IT+
Cohort IT-
0.0
0        20       40       60       80       100      120      140      160      180 200
Time [months]
Cohort IT+ = patients who exercised individually; Cohort IT- = patients who declined individual exercise.
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Table 5. Secondary end-points in groups and cohorts
	Group 1 (n = 32)	Group 2 {n = 60)	Groups (n = 22)	Group 4 (n = 38)	Among groups	P value CR + wCR-	IT+vsII-
Ml	2(6%)	5(8%)	1(5%)	7 (18%)	0.249	0.275	0.149
UAP	6(19%)	22(37%)	1(5%)	8 (21%)	0.008«	0.034«	0.018«
Revascularization	4(13%)	22(37%)	3 (14%)	13(34%)	0.020«	0.855	0.002«
HF	0(0%)	10(17%)	1(5*)	4(11%)	0.017*	0.783	0.020*
M1 + UAP + reva scula rizario n + HF	8 (25%)	36(60%)	4(13%)	21 (55%)	< 0.001«	0.368	< 0.001»
Values are expressed as the number of subjects with the percentage in parentheses.
CR+ = patients who participated in the guided exercise program (comprising patients of groups 1 and 2); CR- = patients who declined to participate in the supervised training (comprising patients of groups 3 and 4); IT+ = patients who exercised individually (comprising patients of groups 1 and 3); IT- = patients who declined individual exercise (comprising patients of groups 2 and 4); MI = myocardial infarction; UAP = unstable angina pectoris; HF = hospitalization for heart failure; * p< 0.05 among groups or between cohorts.
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DISCUSSION
The present study showed that an individual, long-term exercise program has a higher impact on patient survival and rate of MACE than a short-term hospital-based CR program. The potential beneficial effect of supervised exercise training is probably lost when the increased physical activity does not continue also after the guided program is finished.
Physical activities clearly reduce the mortality of coronary artery disease patients 10. While this is encouraging, the success of CR is largely dependent on patient adherence to exercise recommendations during both supervised exercise and self- managed exercise programs. Unfortunately, the data show poor attendance and high dropout rates in guided CR. For example, Hansen et al11 followed 119 patients with coronary artery disease 18 months after inpatient rehabilitation. They found very poor adherence (27%) to the recommended minimal physical activity level during the follow-up, low habitual physical activity in the total group, and progressively worsened cardiovascular disease risk profile
12
of the patients. Similarly, Reid et al   found a significant decrease in habitual physical activity during long-term follow-up after hospital discharge in patients with coronary
13
artery disease. The PIN study   showed that the benefit of CR therapy following myocardial infarction or coronary revascularization is only partially maintained during the following year. The cardiac risk factors improved initially during CR, but deteriorated over the next 12 months.
The beneficial effect of cardiac rehabilitation is nowadays well recognized. However, it remains largely obscure, which characteristics of physical activity and exercise training are the most effective. In general, recommendations of exercise training programmes need to be tailored to the individual's exercise capacity and risk profile, with the aim to reach and maintain the individually highest fitness level possible14. A center-based CR has several advantages, including better exercise supervision with possibilities for correcting the intensity and type of exercise as well as addressing safety issues. On the other hand, supervised CR could be more difficult for some patients to attend. Older age and high co-morbidity are strong predictors for non-attendance 15. A valid alternative is home-based CR. These programs are as effective as center-based CR, but seem hopeful in targeting higher number of patients 16~20. Our study confirmed that long-term individual CR
71
is a very good alterative and could be even more effective than short-time guided exercise program.
21 22
In several studies, such as the HF-ACTION study   '  , exercise led only to a nonsignificant reduction in all-cause mortality or hospitalization. These studies failed to meet the previous expectations most probably due to non-uniform adherence to scheduled physical activity levels and a high percentage of exercise cross-over from training group. In the HF-ACTION study, only approximately 40% of the patients in the exercise group reported weekly exercise volumes at or above the recommended level. Reasons for non-attendance usually varied- patients being "uninterested", illness, work scheduling, and
23
transportation issues   . Patients are not easily convinced to permanently change their lifestyle habits. From the results of our study, it can be deduced that the initial patient enthusiasm for physical exercise and lifestyle changes and their resulting compliance with the exercise recommendations are the most important factors which influencing the effect of exercise programs.
The results of the present study are certainly influenced by the fact that it is nonrandomized study and patients were divided into groups retrospectively according to their acceptance of the exercise recommendations. Patient motivation and willingness to exercise played an important role in the study, and most probably also in their lifestyle behavior. Other potential prognostic factors, such as dietary behavior, weight maintenance or loss, and medication compliance, were not assessed in this study. Nevertheless, all patients were treated according to the evidence-based medicine, and a significant effort was spent on motivating the patients toward nonpharmacological treatment of risk factors, including not only physical exercise, but also dietary and weight recommendations and smoking cessation.
The interpretations of results could be limited by the relatively small sample size of the groups. The study could also be influenced by the differences in age, gender, and diabetic and dyslipidemic patients among the groups. Younger men showed the best compliance to individual aerobic exercise, and this certainly may have influenced the results of our study. However, multivariate Cox regression analysis including baseline covariates (sex, age, diabetes mellitus, and dyslipidaemia - where significant differences were found among groups) revealed group as an independent factor for survival on the borderline of statistical significance.
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In this study, no other outcomes than mortality and mortality was assessed. It has been reported previously that the change in aerobic capacity after CR was related to mortality. Accorging to the study of Vanhees et al, a 1% greater increase in peak oxygen uptake (VO2) after training was associated with a decrease in cardiovascular mortality of 2%. Peak V02, evaluated after a physical training program, and its change in response to training were independent predictors for cardiovascular mortality in patients with coronary
24
artery disease  . Physical training generally increases exercise capacity. The effect of our conducted 3 month training on functional capacity improvement is known and was
25
published previously by our group   . However, patients in our trial had no aerobic capacity evaluation at the end of the follow-up. So that no direct comparison of the impact different training programmes on aerobic capacity is possible.
Another limitation is the fact, that the outpatient individual exercise was performed without any supervision. The information about frequency and intensity was obtained only from patient anamnesis during regular visits to the outpatient department. And finally, the cut off of individual exercise training at minimum duration of 1 hour at least 3 times per week was defined for the group categorization. However, very different types of exercise programs are described in the literature and in some studies a home-based CR had no
18
significant differences from a guided center-based CR programs in the main outcomes , or an outpatient CR led to further improvements than an in-hospital supervised CR . Certainly, further research is required, especially in order to optimize the effectiveness of CR programs and to better understand the mechanisms responsible for the improvements related to CR exercise.
CONCLUSION
In our study, individual long-term exercise program had higher impact on patient survival and rate of MACE than short-term hospital-based guided CR.
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Piepoli MF, Conraads V, Corrä U, Dickstein K, Francis DP, Jaarsma T, McMurray J, Pieske B, Piotrowicz E, Schmid JP, Anker SD, Solal AC, Filippatos GS, Hoes AW, Gielen S, Giannuzzi P, Ponikowski PP. Exercise training in heart failure: from theory to practice. A consensus document of the Heart Failure Association and the European Association for Cardiovascular Prevention and Rehabilitation. Eur J Heart Fail 2011; 13: 347-357.
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012; 33: 1635-1701.
Smith SC Jr, Benjamin EJ, Bonow RO, Braun LT, Creager MA, Franklin BA, Gibbons RJ, Grundy SM, Hiratzka LF, Jones DW, Lloyd-Jones DM, Minissian M, Mosca L, Peterson ED, Sacco RL, Spertus J, Stein JH, Taubert KA. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2011 Update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation 2011; 124: 2458-2473.
Hambrecht R, Gielen S, Linke A, Fiehn E, Yu J, Walther C, Schoene N, Schuler G. Effects of exercise training on the left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial. JAMA 2000; 283: 3095-3101.
Haskell WL, Alderman EL, Fair JM, Maron DJ, Mackey SF, Superko HR, Williams PT, Johnstone IM, Champagne MA, Krauss RM. Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease: The Stanford Coronary Risk Intervention Project (SCRIP). Circulation 1994; 89: 975-990.
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Shephard RJ, Balady GJ. Exercise as cardiovascular therapy. Circulation 1999; 99: 963-972.
7. Benzer W, Platter M, Oldridge NB, Schwann H, Machreich K, Kullich W,
Mayr K, Philippi A, Gassner A, Dörler J, Höfer S. Short-term patient-reported outcomes after different exercise-based cardiac rehabilitation programmes. Eur J Cardiovasc Prev Rehabil 2007; 14(3): 441-447.
8. Williams PT. Vigorous exercise, fitness and incident hypertension, high
cholesterol, and diabetes. Med Sei Sports Exerc 2008; 40(6): 998-1006.
9. Williams PT. Reduced diabetic, hypertensive, and cholesterol medication
use with walking. Med Sei Sports Exerc 2008; 40(3): 433-443.
10. Taylor RS, Brown A, Ebrahim S, Jolliffe J, Noorani H, Rees K, Skidmore
B, Stone JA, Thompson DR, Oldridge N. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and metaanalysis of randomized controlled trials. Am J Med 2004; 116(10): 682-92.
11. Hansen D, Dendale P, Raskin A, Schoonis A, Berger J, Vlassak I, Meeusen
R. Long-term effect of rehabilitation in coronary artery disease patients: randomized clinical trial of the impact of exercise volume. Clin Rehabil 2010; 24(4): 319-327.
12. Reid RD, Morrin LI, Pipe AL, Dafoe WA, Higginson LA, Wielgosz AT,
LeHaye S A, McDonald PW, Plotnikoff RC, Courneya KS, Oldridge NB, Beaton LJ, Papadakis S, Slovinec D Angelo ME, Tulloch HE, Blanchard CM. Determinants of physical activity after hospitalization for coronary artery disease: the Tracking Exercise After Cardiac Hospitalization (TEACH) Study. Eur J Cardiovasc Prev Rehabil 2006; 13(4): 529-537.
13. Wilich SN, Müller-Nordhorn J, Kulig M, Binting S, Gohlke H, Hahmann H,
Bestehorn K, Krobot K, Voeller H. Cardiac risk factors, medication, and recurrent clinical events after acute coronary disease. A prospective cohort study. Eur Heart J 2001; 22(4): 307-313.
14. Vanhees L, Rauch B, Piepoli M, van Buuren F, Takken T, Börjesson M,
Bjarnason-Wehrens B, Doherty P, Dugmore D, Halle M. Importance of
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characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III) . Eur J Prev Cardiol 2012;19: 1333-1356.
15. Cooper AF, Jackson G, Weuinman J, Hörne R. Factors associated with
cardiac rehabilitation attendance: a systematic review of the literature. Clin Rehabil 2002; 16: 541-552.
16. Oerkild B, Frederiksen M, Fischer Hansen J, Simonsen L, Skovgaard LT,
Prescott E. Home-based cardiac rehabilitation is as effective as centre-based cardiac rehabilitation among elderly with coronary heart disease: results from a randomised clinical trial. Age Ageing 2011; 40(1): 78-85.
17. Grace SL, McDonald J, Fishman D, Caruso V. Patient preferences for
home-based versus hospital-based cardiac rehabilitation. / Cardiopulm Rehabil 2005; 25(1): 24-29.
18. Jolly K, Lip GYH, Taylor RS, Raftery J, Mant J, Lane D, Greenfield S,
Stevens A. The Birmingham Rehabilitation Uptake Maximisation study (BRUM): a randomised controlled trial comparing home-based with centre-based cardiac rehabilitation. Heart 2009; 95: 36-42.
19. Dalai HM, Evans PH, Campbell JL, Taylor RS, Watt A, Read KL, Mourant
AJ, Wingham J, Thompson DR, Pereira Gray DJ. Home-based versus hospital-based rehabilitation after myocardial infarction: A randomized trial with preference arms — Cornwall Heart Attack Rehabilitation Management Study (CHARMS). Int J Cardio 2007; 119(2): 202-211.
20. Stolee P, Lim SN, Wilson L, Glenny C. Inpatient versus home-based
rehabilitation for older adults with musculoskeletal disorders: a systematic review. Clin Rehabil 2012; 26: 387-402.
21. Flynn KE, Pina IL, Whellan DJ, Lin L, Blumenthal JA, Ellis SJ, Fine LJ,
Howlett JG, Keteyian SJ, Kitzman DW, Kraus WE, Houston Miller N, Schulman KA, Spertus JA, O'Connor CM, Weinfurt KP. Effects of exercise training on health status in patients with chronic heart failure; HF-ACTION Randomized Controlled Trial. JAMA 2009; 301(14): 1451-1459.
22. Conraads VM, Deaton C, Piotrowicz E, Santaularia N, Tierney S, Piepoli
MF, Pieske B, Schmid JP, Dickstein K, Ponikowski PP, Jaarsma T.
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Adherence of heart failure patients to exercise: barriers and possible solutions: a position statement of the Study Group on Exercise Training in Heart Failure of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2012; 14: 451-458.
23. Blair J, Corrigall H, Angus NJ, Thompson DR, Leslie S. Home versus
hospital-based cardiac rehabilitation: a systematic review. Rural and Remote Health 2011; 11(2): 1532-1547.
24. Vanhees L, Fagard R, Thijs L, Amery A. Prognostic value of training-
induced change in peak exercise capacity in patients with myocardial infarcts and patients with coronary bypass surgery. Am J Cardiol 1995;76(14): 1014-1019.
25. Jancik J, Siegelova J, Homolka P, Svacinova H, Placheta Z, Karpisek Z,
Dobsak P, Dusek J, Fiser B, Toman J, Meluzin J. Exercise training in patients with chronic coronary disease. Scripta Medica 2002;75: 151-156.
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2.5. SOUHRN
V práci byl zkoumán vliv různých druhů tréninku na změnu parametrů zátěžového ergometrického testu, na systolickou a diastolickou funkci LK a na prognózu nemocných s chronickou ICHS. Byl srovnáván především řízený rehabilitační program s individuální pohybovou aktivitou a jejich různé kombinace.
V souboru 64 pacientů nebyly po 1 roce sledování změny hodnocených parametrů ergometrického zátěžového testu dostatečně velké k dosažení statisticky významných rozdílů. Ale i tak bylo možno pozorovat trendy k většímu zlepšení zátěžové kapacity a tolerance, j akožto i zlepšení dalších parametrů u skupin nemocných cvičících intenzivně a trvale doma a to nezávisle na absolvování řízeného rehabilitačního programu. Naopak trend ke zhoršení těchto parametrů byl pozorován u skupin individuálně po dobu sledování necvičících, a to nezávisle na tom, zda absolvovali úvodní 3-měsíční řízený rehabilitační program.
V echokardiografické části studie bylo v souboru 30 nemocných pomocí TDI zjištěno zlepšení celkové systolické funkce LK po 1 roce pouze u té části nemocných, kteří po úvodním 3-měsíčním řízeném tréninku dokázali navázat vlastní tréninkovou aktivitou. Tato studie byla vůbec první, která prováděla i analýzu vlivu tréninku na regionální funkci LK dle povodí věnčitých tepen. V rámci této analýzy bylo zjištěno, že příznivý efekt cvičení byl dán zlepšením regionální kontraktility v povodí uzavřených tepen.
Velmi podobné výsledky byly dosaženy při hodnocení diastolické funkce LK. U 30 nemocných došlo po 1 roce opět ke statisticky významnému zlepšení celkové diastolické funkce pouze u těch nemocných, kteří po řízeném programu trénovali individuálně. I zde byl efekt dán především zlepšení stěn v povodí uzavřených tepen. Je pravděpodobné, že mechanismem zlepšení regionální funkce LK v povodí uzavřené tepny by mohl být pravidelnou tělesnou aktivitou způsobený rozvoj kolaterál. Proto tento předpoklad však naše studie nebyly designovány a tudíž nemohly přinést jeho jednoznačný důkaz.
V prognostické části studie se 152 nemocnými bylo v rámci 94-měsíčního sledování zjištěno, že dlouhodobý individuální trénink zlepšuje přežití nemocných a snižuje množství závažných kardiálních nežádoucích účinků (nestabilní anginy pectoris, nutnosti koronárni revaskularizace, hospitalizace pro srdeční selhání). Výsledky se lišily
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jen na základě dlouhodobě individuální tělesné aktivity. Naproti tomu případný positivní efekt řízeného programu se během času ztratil.
Všechny studie z různých úhlů pohledu a dle rozdílných hodnocených parametrů prokázaly zásadní vliv dlouhodobé tělesné aktivity nemocných s chronickou ICHS. Pouze dlouhodobým pravidelným tréninkem lze dosáhnout zlepšení zátěžové tolerance, zlepšení systolické a diastolické funkce LK a především zlepšení životní prognózy. Práce neměla v úmyslu nikterak zpochybnit důležitost řízených rehabilitačních programů, které mají jistě nesporné výhody, jako je přizpůsobení tělesné aktivity na míru individuálním pacientům, nastartování pohybového režimu u nemocných, kteří ho dosud neměli a potenciálně větší bezpečnost tělesné aktivity u rizikových jedinců. Pokud ale chceme nemocným zlepšit jejich prognózu, nebo alespoň jejich srdeční funkci, je třeba je motivovat k, pokud možno trvalé, změně jejich životního stylu, a to především směrem k pravidelné tělesné aktivitě.
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2.6. ZÁVĚR
Rehabilitační program je důležitou složkou léčby nemocných s chronickou ICHS. Dlouhodobá individuální pohybová aktivita přináší nemocným významně větší prospěch než krátkodobý řízený rehabilitační program, a to jak ve smyslu zlepšení systolické a diastolické funkce LK, tak i zlepšení prognózy. Pravidelná aerobní tělesná aktivita by se měla stát trvalou součástí životního stylu nemocných s chronickou ICHS.
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2.7. PŘÍLOHY - ORIGINÁLY PUBLIKOVANÝCH PRACÍ
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Srovnání řízeného a nekontrolovaného aerobního tréninku nemocných s chronickou ischemickou chorobou srdeční
- R. Panovský, R. Jančár, J. Meluzín, J. Jančík, L. Kožantová, L. Mífková, J. Siegelová, V. Kincl -
MUDr. Roman Panovský, Ph.D.
Narodil se v roce 1970. Po promoci na LF MU v Brně (1994) nastoupil na I. interní kardioangiologickou kliniku FN U sv. Anny v Brně, kde působí dosud. Zde pracuje především na standardním kardiologickém oddělení, v ambulanci pro konzervativní terapii ischemické chorby srdeční a v echokardiografické laboratoři. Atestaci z vnitřního lékařství I. stupně složil v roce 1997, atestaci z kardiológie v roce 2002. V roce 2003 obhájil doktorandskou disertační práci na téma Perspektivy ultrazvukové charakteristiky tkání v kardiológii (Využití v hodnocení viability myokardu). Je autorem nebo spoluautorem 60 publikací. Mezi hlavní odborné zájmy patří neinvazivní kardiológie, echokar-diografie, rehabilitace pacientů s ischemickou chorobou srdeční a buněčná léčba kardiologických pacientů.
Klíčová slova
tělesný trénink - ischemická choroba srdeční - ergometrie
Souhrn
Cíl: Cílem práce bylo srovnat parametry opakovaného ergometrického zátěžového testu nemocných s chronickou ischemickou chorobou srdeční (ICHS) s řízeným a nekontrolovaným aerobním tréninkem. Soubor a metodologie: 64 nemocných s chronickou ICHS bylo rozděleno do 4 skupin podle intenzity a druhu aerobního tréninku. Do skupiny A bylo zařazeno 17 pacientů, kteří se zúčastnili řízeného 3měsíčního rehabilitačního programu a navázali na něj individuálním cvičením. Ve skupině B bylo 22 pacientů, kteří absolvovali jen řízený program bez následného individuálního tréninku. Ve skupině C bylo 10 pacientů, kteří neabsolvovali rehabilitační program, ale doma intenzivně cvičili. Do skupiny D bylo zařazeno 15 pacientů, kteří se nezúčastnili rehabilitačního programu, ani doma necvičili. Ergometrické testy byly provedeny před zařazením do studie a po 1 roce sledování. Byly hodnoceny změny těchto parametrů: celkový čas zátěže, celkově vykonaná práce, pracovní kapacita, pracovní tolerance, čas do stenokardií, deprese ST-úseku ve svodu V5 při maximální zátěži. Výsledky: Pro nemocné ve skupině C byl zjištěn trend ke zlepšení ve všech hodnocených parametrech s výjimkou prohloubení deprese úseku ST ve svodu V5 při maximální zátěži. Ve skupině A nemocní dosáhli delšího celkového času zátěže, vykonali větší celkovou práci a měli vyšší pracovní toleranci, v ostatních parametrech došlo ke zhoršení. Pacienti ze skupin B a D se zhoršili ve všech parametrech. Všechny rozdíly v jednotlivých skupinách ani mezi skupinami navzájem nebyly statisticky významné. Závěry: Parametry opakovaného ergometrického testu nemocných podstupujících jednotlivé typy rehabilitačních programů se od sebe statisticky nelišily. Byl konstatován trend ke zlepšení zátěžových parametrů u skupin nemocných cvičících intenzivně a trvale doma a trend ke zhoršení u skupin individuálně necvičících, a to nezávisle na absolvování úvodního řízeného rehabilitačního programu.
Keywords
physical training - coronary heart disease - ergometry
Summary
Comparison of controlled and uncoltrolled aerobic physical training of patients with chronic coronary heart disease. Purpose: The purpose of this study was to compare the effect of the controlled or uncontrolled aerobic physical training in patients with stable coronary artery disease (CAD). Methogology and group: 64 patients with stable CAD were divided into 4 groups according to the intensity and form of aerobic training. The group A comprised 17 patients, who had taken part in a conducted training program for 3 months and have continued with individual training. 22 patients (group B) had participated in the training program without follow-up individual exercise. Patients in groups C and D had not taken part in the controlled training program. 10 group C patients had intensively exercised at home (cycling, running, etc.), whereas 15 group D patients had not exercised at all. ECG (electrocardiogram) stress tests ona bicycle ergometer were performed before the training and 1 year later. The changes of following parameters were assessed: the total exercise duration, total work load, exercise capacity, exercise tolerance, the time to onset of angina and ST-segment depressions at the lead V5 in the maximal load. Results: Patients in the group C exhibited trends to improve in all parameters, with the exception of ST-segment depression at the lead V5 in the maximal exercise load. Patients in the group A exhibited trends to reach longer exercise duration, higher total work load and higher exercise capacity comparing with the basal stress test. Patients in the group B and D exhibited trends to worsen all parameters. Differences in groups and between groups were not statistically significant. Conclusion: In patients with stable CAD and different types of aerobic physical training, exercise parameters did not statistically differ. The trend toward improving stress parameters was identified only in patients, who had intensively exercised at home, independently of participating in the conducted training program.
Kardiol Rev 2005; 7(2)
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Srovnání řízeného a nekontrolovaného aerobního tréninku nemocných s chronickou ischemickou chorobou srdeční
Uvod
Příznivý vliv fyzické aktivity na kardiovaskulární systém je nesporný nejen u zdravých jedinců, ale i u nemocných s kardiovaskulární chorobami. Pravidelná aerobní zátěž nemocných se srdečními chorobami zlepšuje kvalitu života, omezuje jejich symptomy a snižuje mortalitu [1-8]. Děje se tak příznivým ovlivněním rizikových faktorů vzniku a progrese především ischemické choroby srdeční. Dochází k ovlivnění lipidového metabolizmu snížením LDL- a zvýšením HDL-cholesterolu [5,9-10]. Zvyšuje se také senzitivita k inzulínu a spolu s dietními opatřeními dochází k redukci obezity [5,11]. Dochází ke snížení klidové sym-patikoadrenální aktivity, což spolu s omezením agregace krevních destiček a poklesem plazmatických hladin fibrinogenu vede ke snížení rizika vzniku akutního koronárního syndromu.
U nemocných s ischemickou chorobou srdeční má pravidelné cvičení řadu příznivých účinků vedoucích ke zmírnění anginózních potíží i objektivních známek ischemie myokardu při zátěžových testech - zvýšení tolerance zátěže, snížení depresí ST-úseku atd. Tyto změny jsou způsobeny několika mechanizmy - pravidelný trénink způsobuje jednak snížení srdeční práce tím, že se sníží spotřeba kyslíku (snížením tepové frekvence a krevního tlaku) [4,12-16] a zároveň má vliv i na zlepšení přísunu kyslíku (rozšířením epikardiálních koro-nárních arterií, zvýšením denzity myokardiál-ních kapilár a rozvojem kolaterál) [ 17-18]. Při dostatečně intenzivní zátěži (spolu s redukcí ostatních rizikových faktorů) může dojít k zastavení progrese, příp. i k mírné regresi angio-grafických změn na koronárních arteriích [4,13,19-20],
Hledají se optimální druhy a režimy tréninku (např. aerobní trénink s posilováním nebo bez něj), různé frekvence a délky cvičení. Prakticky všechny práce hodnotící nejrůznější řízené tréninkové programy přinášejí důkazy o jejich příznivých efektech. Existuje ale i dostatek prací, popisujících zlepšení stavu pacientů, kteří se o svůj pohybový režim starají více či méně sami. Dosud chybí studie srovnávající řízené a individuální nekontrolované aerobní cvičení. Proto bylo cílem této práce srovnat parametry opakovaného ergometrického zátě-
žového testu nemocných s chronickou ischemickou chorobou srdeční s řízeným a nekontrolovaným aerobním tréninkem.
Materiál a metodologie_
Do studie bylo zařazeno 64 nemocných s chronickou ischemickou chorobou, kteří splňovali následující kritéria: onemocnění koronárních tepen bylo ověřeno koronarografií (zúžení průměru lumina tepny > 50 % na alespoň jedné hlavní koronárni tepně); bez anamnézy prodělané ataky nestabilní anginy pectoris nebo infarktu myokardu v posledních 3 měsících před
zařazením do studie; bez anamnézy revaskula-rizace myokardu koronárni angioplastikou nebo aortokoronárním bypassem v posledních 3 měsících před zařazením do studie; nepřítomnost významné chlopenní vady a destabilizované hypertenze. Všem nemocným byl opakovaně a důkladně vysvětlen příznivý účinek tělesné aerobní aktivity na jejich zdravotní stav, byla jim doporučena pravidelná aerobní aktivita a nabídnut 3měsíční řízený rehabilitační program. Všichni nemocní podstoupili ergo-metrický zátěžový test při zařazení do studie a po 1 roce sledování.
Graf 1. Srovnání změn celkového času zátěžového testu na konci sledování ve srovnání se vstupním testem v jednotlivých skupinách.
6	p kW			skupina H A      1 B      1 c D
5	4,8			
4				3,7
3	-			
2	-			
1	-			
0 -1	1			
				-0,8
-2				
-3				p = NS
-4			-3,5	
Graf 2. Srovnání změn celkové práce během zátěžového testu na konci sledování ve srovnání se vstupním testem v jednotlivých skupinách.
Tab. 1. Charakteristiky pacientů.
skupina	počet	věk (roky)	nadváha (%) HT(%)		DM (%)	DLP (%)	AP	IM (%)	počet tepen	CABG(%)	PTCA (%)	EF(%)
A	17	66	71	65	24	82	1,2	53	2,3	18	41	48
B	22	66	82	45	23	82	1,3	86	1,6	14	41	45
C	10	60	80	70	20	90	1,3	90	1,9	20	70	43
D	15	63	67	73	20	73	1,4	60	2,2	20	27	49
HT = hypertenze, DM = diabetes mellitus, DLP = dyslipoprotienemie, AP = stupeň anginy pectoris podle kanadské klasifikace (CCS), IM = počet nemocných po infarktu myokardu, počet tepen = průměrný počet tepen postižených významnou stenozou, CABG = počet nemocných po aortokoronárním bypassu, PTCA = počet nemocných po perkutánní koronárni angioplastice, EF = ejekční frakce levé komory.
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Srovnání řízeného a nekontrolovaného aerobního tréninku nemocných s chronickou ischemickou chorobou srdeční
Zpětně byly nemocní rozděleni do 4 skupin podle intenzity a druhu jejich aerobního tréninku. Do skupiny A bylo zařazeno 17 pacientů (14 mužů a 3 ženy, průměrný věk 66+11 let), kteří se zúčastnili řízeného rehabilitačního programu a doma na něj navázali individuálním cvičením. Ve skupině B bylo 22 pacientů (14 mužů a 8 žen, průměrný věk 66 + 8 let), kteří absolvovali jen řízený program bez následného individuálního tréninku. Ve skupině C bylo 10 pacientů (7 mužů a 3 ženy, průměrný věk 60 + 8 let), kteří neabsolvovali rehabilitační program, ale doma intenzivně cvičili. Do skupiny D bylo zařazeno 15 pacientů (12 mužů a 3 ženy, průměrný věk 63 + 8 let), kteří se nezúčastnili rehabilitačního programu, ani doma necvičili. Další charakteristiky jednotlivých skupin jsou uvedeny v tab. 1. Rozdíly mezi jednotlivými skupinami nebyly statisticky významné. Farmakologickou léčbu nemocných ukazuje tab. 2.
Řízený rehabilitační program probíhal na Klinice funkční diagnostiky a rehabilitace Fakultní nemocnice U svaté Anny v Brně. Nemocní, kteří souhlasili s absolvováním tohoto programu, podstoupili před jeho zahájením spiroergomet-rické vyšetření k nastavení úrovně aerobního cvičení. Vyšetření bylo provedeno v ranních hodinách, při ponechané medikamentózni léčbě. Vlastní vyšetření začínalo 3minutovou adaptací vsedě na veloergometru. Následovaly 2minutové zátěže od 20 W, zvyšované vždy o 20 W, v jejichž průběhu byly měřeny ventilačně respirační parametry. Ty byly sledovány přístrojem Pulmonary Function System 1070 (Med Graphics, USA). Byl hodnocen symptomy limitovaný minutový příjem kyslíku (V02) jako kritérium kardiorespirační funkční zdatnosti a také byla určena hodnota anaerobního prahu k nastavení vhodné intenzity zatížení. Hodnota anaerobního prahu byla pro potřeby studie vyjádřena ve W, odpovídající hodnotě tepové frekvence a stupněm Borgovy škály subjektivního vnímání namáhavosti příslušného zatížení. Během celého vyšetření včetně doby restituce byl monitorován 12svodový elektrokardiogram (Schiller CS 100, USA), v klidu a na konci každé zátěže byl měřen krevní tlak.
Vlastní rehabilitační program trval 3 měsíce, během kterých nemocní cvičili 3krát týdně 60 minut. Cvičební jednotka se skládala ze zahřívací fáze (10 minut), vlastního aerobního cvičení na veloergometru, na úrovni aerobního prahu doplněná silovým tréninkem (40 minut) a ze závěrečné fáze relaxační (10 minut).
Individuální aktivita byla doporučována jako minimálně 3krát týdně 60 minut aerobního cvičení (jízda na kole nebo na rotopedu, běh, plavání). Plnění tohoto doporučení bylo zjišťováno pouze anamnestický od pacienta a nebylo ani kontrolováno, ani prověřováno.
Ergometrické zátěžové testy byly provedeny na přístroji Ergo-line před zařazením do stu-
die a po 1 roce sledování, vždy s vysazenou medikací. Bylo započato zátěží 0,5 W/kg, která byla schodovitě zvyšována po 3 minutách vždy o 0,5 W/kg. Test byl ukončen při průkazu ischemie (objevení nebo prohloubení depresí ST-úseku o alespoň 0,2 mV), při dosažení průměrné maximální tepové frekvence vzhledem k věku, při vzestupu krevního tlaku nad 250/130 mmHg, při dosažení hranice subjektivního maxima. Rozdíl mezi zátěžovým testem na konci sledování a na začátku studie byl hodnocen pomocí změny těchto parametrů: celkový čas zátěže, celkově vykonaná práce, pracovní kapacita, pracovní tolerance, čas do stenokardií a deprese ST-úseku ve svodu V5
0
1—			
-			
	-95		-93
			
při maximální zátěži (srovnáno dle maximální zátěže vstupního testu).
Ejekční frakce byla před zařazením do studie stanovena retrográdní levostrannou ventriku-lografií.
Výsledky srovnání změny parametrů ergomet-rických testů nemocných jsou uvedeny jako průměry směrodatná odchylka. Výsledky jednotlivých skupin byly porovnány parametrickou statistickou metodou ANOVA. Hodnoty p < 0,05 byly považovány za významné. Normální rozložení hodnot bylo testováno pomocí Kolmogorov-Smirnovovým testem s výsledkem p > 0,2.
skupina B A       I B      I c        I D
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-127 p = NS
Graf 3. Srovnání změn času po stenokardií během zátěžového testu na konci sledování ve srovnání se vstupním testem v jednotlivých skupinách.
Graf 4. Srovnání změn depresí ST úseku ve svodu V5 při maximální zátěži na konci sledování ve srovnání se vstupním testem v jednotlivých skupinách.
Tab. 2. Farmakologická léčba nemocných.
Skupina salicyláty (%) BB (%)    CaA(%)   nitráty (%) ACEI (%)    ATM (%) statiny(%)
A	100	94	53	53	53	12	88
B	95	100	27	68	68	0	82
C	90	100	10	70	70	10	80
D	100	93	40	80	33	0	73
BB = betablokátory, CaA = kalciový antagonisté, ACEI = antagonisté angiotenzin-konvertujícího enzymu, ATM = sartany.
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Srovnání řízeného a nekontrolovaného aerobního tréninku nemocných s chronickou ischemickou chorobou srdeční
Výsledky
Vliv různých typů tréninku na změnu parametrů ergometrického zátěžového testu přehledně znázorňují grafy 1-6. Nalezené změny zátěžových testů v jednotlivých skupinách nedosáhly statistické významnosti. Nemocní cvičící od začátku individuálně (skupina C) vykazovali trend ke zlepšení ve všech hodnocených parametrech s výjimkou prohloubení deprese úseku ST ve svodu V5 při maximální zátěži (prohloubení při kontrolním testu o 0,006 + 0,018 mV, p = NS). Při kontrolním testu dosáhli o 30 + 108 s delší doby zátěže, vykonali o 3,7 + 15,0 kW větší celkovou práci, dosáhli vyšších hodnot pracovní kapacity o 0,01 + 0,52 W/kg a pracovní tolerance o 0,16 + 0,33 W/kg a prodloužil se u nich čas do stenokardií o 72 + 408 sekund (vše p = NS).
Nemocní, kteří absolvovali řízený program a následně individuálně cvičili (skupina A), dosáhli nevýznamně delšího celkového času zátěže (zlepšení o 26 + 73 s), vykonali větší celkovou práci (o 4,8 + 1 4,2 kW) a měli vyšší pracovní toleranci (o 0,03 + 0,36 W/kg) (vše p = NS). V ostatních parametrech došlo k mírnému zhoršení - pracovní kapacita poklesla o 0,06 + 0,48 W/kg, ST deprese ve svodu V5 při maximální zátěži se prohloubily o 0,002 + 0,014 mV a doba do vzniku stenokardií se zkrátila o 95 + 269 s (vše p = NS).
Pacienti necvičící vůbec (skupina D) nebo necvičící po absolvování RHB programu (skupina B) se zhoršili prakticky ve všech sledovaných parametrech. Pacienti ve skupině B vydrželi kontrolní zátěžový test o 28 + 51 s kratší dobu, vykonali o 3,5 + 5,9 kW menší celkovou práci, zhoršili svoji pracovní kapacitu o 0,06 + 0,28 W/kg a pracovní toleranci o 0,08 + 0,20 W/kg a stenokardie popisovali o 93 + 219 s dříve (vše p = NS). Menší deprese úseku ST ve svodu V5 o 0,009 + 0,018 mV (p = NS) je dán menší celkovou prací při kontrolním testu.
Nemocní ze skupiny D měli nižší čas zátěže o 8 + 95 s, menší celkově vykonanou práci o 0,8 + 13,3 kW, menší pracovní kapacitu o 0,23 + 0,36 W/kg a pracovní toleranci o 0,07 + 0,25 W/kg, stenokardie udávali o 127 + 320 s dříve a deprese úseku ST ve svodu V5 se prohloubily o 0,009 + 0,012 mV (vše p = NS).
Rozdíly mezi jednotlivými hodnocenými skupinami nebyly statisticky významné. Během obou sledovaných forem fyzického tréninku nenastala žádná závažná komplikace.
Diskuse
V naší práci se parametry opakovaného ergometrického zátěžového testu nemocných s chronickou ischemickou chorobou srdeční podstupující jednotlivé typy rehabilitačních programů od sebe statisticky významně nelišily. Počty nemocných a změny hodnocených parametrů
nebyly dostatečně velké k dosažení statisticky významných rozdílů, nicméně byly nalezeny jasné trendy k většímu zlepšení zátěžové kapacity a tolerance u skupin nemocných cvičících intenzivně a trvale doma a to nezávisle na absolvování řízeného rehabilitačního programu.
Nebylo překvapením, že se zlepšili právě pacienti, kteří se cvičení věnují intenzivně sami. Mírně překvapil fakt, že se na výsledcích více neprojevil vstupní řízený trénink. Pravděpodobně je tomu tak z důvodů provedení kontrolních testů až 9 měsíců po ukončení řízeného tréninku. Je známo, že čím je trénink intenzivnější, tím výraznější efekt se dá očekávat na zátěžovou toleranci [21]. Zatímco se u nemocných, pokračujících po absolvování programu ve cvičení, projevil při kontrolních testech hlavně intenzivní dlouhodobý trénink, u těch pacientů, kteří cvičit přestali, byly naopak funkční parametry na úrovni, jako kdyby necvičili vůbec.
I v ostatních studiích zaměřených v minulosti na tuto problematiku byly nalezeny vlivy pravidelného cvičení na zátěžové parametry. Studie European Heart Failure Training Group,
publikovaná v roce 1998 [22], uvádí statisticky významné 17% zvýšení celkového času zátěže u pravidelně cvičících pacientů, a to bez rozlišení, zda účastníci cvičili doma, nebo v nemocnici. Také udává větší účinnost u kombinace cvičení na ergometru a rytmiky oproti samotnému cvičení na ergometru.
Individuální tělesnou aktivitou se zabývali i Adachi et al [23], kteří zkoumali vliv různých intenzit tréninku na funkci levé komory. Jejich pacienti cvičili doma - měli za úkol chodit rychlou chůzí 15 minut 2krát denně, 5 dní v týdnu, po dobu 2 měsíců. Intenzitu zátěže si řídili podle tepové frekvence. U 29 nemocných po infarktu myokardu prokázali, že trénink jakékoliv intenzity zlepšuje pracovní kapacitu, ale pouze trénink o vysoké intenzitě zlepšuje funkci levé komory vyjádřenou tepovým objemem a ejekční frakcí.
Na poměrně velkém souboru 113 pacientů s ICHS, kteří cvičili pravidelně denně doma na rotopedu a své cvičení si zapisovali do přiděleného log booku, prokázali Niebauer et al [13] po 6 letech sledování 28% zvýšení pracovní kapacity a zpomalení progrese koronárních
0,05
.W/kg
skupina ^| A 0,001
Graf 5. Srovnání změn pracovní kapacity na konci sledování ve srovnání se vstupním testem v jednotlivých skupinách.
0,2 rw/kg 0,15 -
0,1 0,05 0
-0,05 _ -0,1 _
skupina ^| A 0,016
0,003
-0,008
IT
-0,007
p = NS
Graf 6. Srovnání změn pracovní tolerance na konci sledování ve srovnání se vstupním testem v jednotlivých skupinách.
Kardiol Rev 2005; 7(2)
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Srovnání řízeného a nekontrolovaného aerobního tréninku nemocných s chronickou ischemickou chorobou srdeční
stenóz. K podobným výsledkům dospěly i další studie [24]. Pravidelné cvičení neovlivňuje pouze fyzickou výkonnost, ale i celkovou kvalitu života. Focht et al [25] porovnávali 2 druhy tělesného tréninku (pouze řízený versus řízený následovaný individuálním cvičením) u 147 osob starších 50 let a dle dotazníků zjistili zlepšení kvality života (health-related quality of life) při obou typech tréninku.
Naše práce, ve shodě s výše uvedenými studiemi, ukazuje, že nej důležitější je pravidelnost a kontinuita cvičení. Řízené rehabilitační programy mají přesto několik nezastupitelných úloh. Ukazují nemocným styl cvičení, posilováním jim umožňují dosáhnout lepší fyzické kondice, která je nutná pro další pokračování ve cvičení na dostatečné úrovni zátěže doma. Velmi významná je u pacientů, u kterých hrozí zdravotní komplikace už při malém stupni zátěže a je u nich velké riziko zdravotních komplikací, které vyžadují lékařský dohled, příp. intervenci. Jedno z možných řešení, jak spojit řízenou a individuální tělesnou aktivitu, naznačují němečtí autoři z Heidelbergu - jejich pacienti cvičili nejdříve 3 týdny intenzivně v nemocnici (6krát denně!), následně jim byl zapůjčen rotoped a cvičili individuálně doma (2krát denně po 30 minutách) s pravidelnými společnými cvičeními v nemocnici (2krát týdně). Tímto velmi intenzivním tréninkem dosáhli u svých pacientů za 12 měsíců nejenom snížení zátěží vyvolané ischemie o 54 % [26], ale prokázali i zpomalení progrese koronárni aterosklerózy [20]. Rovněž zastavení progrese koronárních aterosklerotických lézí prokázali Hambrecht et al [27] u 29 chronických ischemiků pomocí 12měsíčního individuálního tréninkového programu (minimálně 30 minut denně jízdy na ergometru) zahájeného 3 týdny společného cvičení v nemocnici (6krát denně 10 minut šlapání na ergometru).
Podobně Hofman-Bang [4] nabídli svým pacientům 12měsíční individuální tréninkový program spojený s pokusem o změnu životního stylu, který zahrnoval vstupní 4týdenní „zaučení". Na 151 nemocných po PTCA (perkutánní transluminální koronárni angioplastice) ukázali zvýšení pracovní kapacity a snížení počtu hospitalizací během následujících 12 měsíců po ukončení programu. Z hlediska praktického využití mají tyto rehabilitační modely zásadní limitaci ve vstupní 3týdenní, respektive 4týdenní hospitalizaci, nicméně jistě by se podobné spojení řízené a individuální aktivity dalo přizpůsobit reálným možnostem a komfortu pacientů.
Hlavními limitacemi naší práce je malé množství nemocných v jednotlivých skupinách a krátká doba sledování. Spolu s očekávaně nevelkými změnami jednotlivých ergometric-kých parametrů po 1 roce sledování se nedá předpokládat statistická významnost rozdílů mezi skupinami. Vzhledem k jasným trendům
je plánováno pokračování studie s větším počtem nemocných a s delší dobou sledování.
Závěr_
Parametry opakovaného ergometrického zátěžového testu nemocných podstupující jednotlivé typy rehabilitačních programů se od sebe statisticky významně nelišily. Byl nalezen trend zlepšení zátěžových parametrů u skupin nemocných cvičících intenzivně a trvale doma a trend zhoršení u skupin individuálně necvičících, a to nezávisle na absolvování úvodního řízeného rehabilitačního programu. Je třeba dbát zvýšeného důrazu na informování a edu-kaci nemocných s ICHS ve smyslu zintenzívnění jejich pohybového režimu.
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20. Schuler G, Hambrecht R, Schliert G et al. Myocardial perfusion and regression of coronary artery disease in patients on a regimen of intensive exercise and low fat diet. J Am Coll Cardiol 1992; 19: 34-42.
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Doručeno do redakce 9. 2. 05 Přijato k otištění po recenzi 17. 4. 05
M U D r. Roman Panovský, Ph.Dj M U D r. Radek Jančár prof. M U D r. Jaroslav Meluzín, CSc. MUDr. Vladimír Kincľ as. MUDr. Jiří Jančík, Ph.D.? Mgr. Lucie Kožantová? Mgr. Leona Mífkováš prof. MUDr. Jarmila Siegelová, DrSc2
1 I. interní kardioangiologická klinika FN U sv. Anny, Brno 2 Klinika funkční diagnostiky a rehabilitace, FN U sv. Anny, Brno
72
www.kardiologickarevue.cz
Physiol. Res. 60: 869-875, 2011
The Effect of Regular Physical Activity on the Left Ventricle Systolic Function in Patients With Chronic Coronary Artery Disease
R. PANOVSKÝ1, P. KUKLA1, R. JANČÁR1, J. MELUZÍN1, J. JANČÍK2, V. KINCL1, K. POLOKOVÁ1, L. MÍFKOVÁ2, A. HAVELKOVÁ2, R. LÁTALOVÁ2, P. DOBŠÁK2, M. PEŠL1
xFirst Department of Internal Medicine/Cardioangiology, International Clinical Research Center-ICRC, St. Anne's Hospital, Masaryk University, Brno, Czech Republic, 2 Department of Functional Diagnostic and Rehabilitation, St. Anne's Hospital, Masaryk University, Brno, Czech Republic
Received February 15, 2011 Accepted August 3, 2011 On-line October 12, 2011
Summary
The purpose of this study was to assess the influence of aerobic training on the left ventricular (LV) systolic function. Thirty patients with stable coronary artery disease, who had participated in the conducted 3-month physical training, were retrospectively divided into 2 cohorts. While patients in the cohort I (n=14) had continued training individually for 12 months, patients in the cohort II (n=16) had stopped training after finishing the conducted program. Rest and stress dobutamine/atropine echocardiography was performed in all patients before the training program and 1 year later. The peak systolic velocities of mitral annulus (Sa) were assessed by tissue Doppler imaging for individual LV walls. In addition, to determine global LV systolic longitudinal function, the four-site mean systolic velocity was calculated (Sa glob). According to the blood supply, left ventricular walls were divided into 5 groups: A- walls supplied by nonstenotic artery; B- walls supplied by coronary artery with stenosis < 50 %; C- walls supplied by coronary artery with stenosis 51-70 %; D- walls with stenosis of supplying artery 71-99 %; and E- walls with totally occluded supplying artery. In global systolic function, the follow-up values of Sa glob in cohort I were improved by 0.23±0.36 as compared with baseline values at rest, and by 1.26±0.65 cm/s at the maximal load, while the values of Sa glob in cohort II were diminished by 0.53±0.22 (p=NS), and by 1.25±0.45 cm/s (p<0.05), respectively. Concerning the resting regional function, the only significant difference between cohorts in follow-up changes was found in walls E: 0.37±0.60 versus -1.76±0.40 cm/s (p<0.05). At the maximal load, the significant difference was found only in walls A (0.16±0.84 versus -2.67±0.87 cm/s; p<0.05). Patients with
regular 12-month physical activity improved their global left ventricle systolic function mainly due to improvement of contractility in walls supplied by a totally occluded coronary artery.
Key words
Coronary artery disease • Aerobic training • Left ventricle systolic function
Corresponding author
R. Panovský, First Department of Internal Medicine/ Cardioangiology, International Clinical Research Center - ICRC, St. Anne's Hospital, Masaryk University, Pekařská 53, 656 91 Brno, Czech Republic. Fax: +420 543182205. E-mail: panovsky@fnusa.cz
Introduction
Beneficial effects of cardiac rehabilitation (CR) on secondary prevention of patients with coronary artery disease are now well-established. The major objective benefits are an increased exercise capacity (Hambrecht et al. 2000) and reduced rates of cardiac events and mortality (Oldridge et al. 1988, Hadkell et al. 1994). In addition, beneficial effects on coronary risk factors -blood pressure, lipid levels, glucose metabolism, body weight, as well as on the endothelial function and psychological well-being were proved (Shephard and Balady 1999).
On the other hand, only limited data exists
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concerning the effect of CR on left ventricular (LV) function. Some authors suggest improvements in cardiac function (Belardinelli et al. 1996, Giannuzzi et al. 1997, Hambrecht et al. 2000, Klecha et al. 2007), whereas others have not found any significant differences between exercise training groups and controls (Dubach et al. 1997, Giannuzzi et al. 2003). The different results may be due to differences in intensity and duration of training, measurement techniques or patient populations. However, in majority of the studies, LV function has been evaluated by LV ejection fraction (EF) measurements. It is well known that LVEF quantification using standard two-dimensional (2D) echocardiography is strongly dependent on image quality and endocardial border delineation.
Tissue Doppler imaging (TDI) is an echocardiographic technique employing the Doppler principle to measure the velocity of myocardium. Pulsed-TDI permits quantification of regional longitudinal myocardial velocities with high temporal resolution and is feasible even in poor acoustic windows. Hence, TDI offered a potentially more accurate quantitative assessment of both regional and global LV function including even more minor changes in systolic LV function that are not detectable during 2D echocardiographic evaluation of LVEF.
The purpose of this study was to assess the influence of aerobic training on the LV systolic function using TDI measurements.
Methods
Patient population and study protocol
The study comprised 30 patients with stable coronary artery disease (proved by the coronary angiography performed before the study). All of them had participated in the conducted 3-month physical CR training. The continuation of physical training was recommended to all patients. After 1 year period, these patients were retrospectively divided into 2 cohorts. While patients in the cohort I (n=14) had continued training individually for 12 months, patients in the cohort II (n=16) had stopped training after finishing the conducted CR program.
Rest and stress dobutamine/atropine echocardiography was performed in all patients before the training program and 1 year later. For the evaluation of regional systolic LV function, the pulsed TDI was used.
According to the blood supply, LV walls were
divided into 5 groups: A- walls supplied by nonstenotic artery; B- walls supplied by coronary artery with stenosis <50 %; C- walls supplied by artery with stenosis 51-70 %; D- walls with stenosis of supplying coronary artery 71-99 %; and E- walls with totally occluded supplying artery.
The study was in accordance with the Declaration of Helsinki (2000) of the World Medical Association, was approved by the institutional ethics committee and written consent was obtained from each patient.
Physical training
All patients had participated in the conducted outpatient CR. The program offered 3 months of 3 times per week sessions. Each session lasted for 60 minutes and consisted of 3 different phases: 10 minutes warm-up, period of aerobic exercise on bicycle ergometer with load intensity at the level of anaerobic threshold (20 min), period of resistance training performed on combined training machine (20 min), and relaxation period (10 min). Aerobic exercise intensity was individually prescribed according to symptom-limited spiroergometry (Blood Gas Analyser, MedGraphics, USA) that was provided before training period for the evaluation of anaerobic threshold.
The 9-months individual training of cohort I consisted of regular physical activity performed for a minimum of one hour at least three times a week. As a regular physical activity the patients have been asked to choose either cycling, riding a velo-ergometer or swimming.
Echocardiography
Using commercially available equipment Philips Sonos 5500 (Andover, USA) with a 2.5 MHz transducer, echocardiographic examinations were performed in one centre by one experienced echocardiographer. 2D images of standard views and pulsed TDI of apical 4- and 2-chamber views were acquired and recorded on videotape for off-line analyses. The peak systolic velocities of myocardium adjacent to the mitral annulus (Sa) were assessed by TDI for individual LV walls: septum, lateral, anterior, and inferior walls. In addition, to determine global LV systolic longitudinal function, the four-site mean systolic velocity was calculated (Sa glob). Velocities were evaluated at rest and at the maximal load.
Dobutamine echocardiography was performed in all patients. Dobutamine was infused with mechanical
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The Effect of Physical Activity on the Left Ventricle Systolic Function 871
pump, starting at a dose of 5 ug/kg/min. At 3-minute intervals, the dose was increased incrementally to 10, 20, 30, 40 ug/kg/min until a maximal dose was reached or target heart rate was attained. Intravenous atropine was given in one bolus dose of 0.5 mg if the target heart rate was not reached. After the test has been terminated, patients were monitored until baseline condition returned.
Statistical analysis
The changes of global and regional systolic function of individual LV wall groups were compared between cohorts at rest and at the maximal load. To assess normal distribution of variables, the Kolmogorov-Smirnov test was used. An unpaired t-test and Mann-
Whitney U test were applied to compare the values of parameters between cohorts; p<0.05 was considered statistically significant.
Results
Baseline characteristics and coronary angiography findings of patients are shown at Table 1 and 2. The majority of parameters have been similar in the two groups - just differences between the number of men and women and the difference between patients age in both cohorts have been found. No serious adverse events were found in either group during the follow-up.
Table 1. Characteristics of the study population.
Parameter		Cohort I (n:		= 14)			Cohort II (	n = 16)
Age (years)		60		(10)			69*	(8)
Men		13		(93 %)			8*	(50 %)
Diabetes mellitus		4		(29 %)			5	(31 %)
Hypertension		14		(100 %)			16	(100 %)
Hyperlipidemia		14		(100 %)			15	(94 %)
Previous myocardial infarction		10		(71 %)			9	(57 %)
LVEF (%)		50.4		(2.9)			47.9	(2.7)
No of stenotic arteries (>70 %>)		2.1		(0.2)			1.6	(0.2)
Medication								
Aspirin		14		(100 %)			15	(94 %)
Beta blocker		14		(100 %)			16	(100 %)
ACE inhibitor		10		(71 %)			11	(70 %)
Statin		13		(93 %)			16	(100 %)
Diuretics		4		(29 %)			5	(31 %)
Nitrates		8		(57 %)			11	(69 %)
The values are expressed as the mean supplied by standard error (in parentheses) or number (%) of subjects. LV =								left ventricle; EF =
ejection fraction; No = number; ACE =	angiotensin-converting enzyme; *			p<0.05 between cohorts.				
Table 2. Coronary angiography finding in cohorts.								
Cohort		I (n = 14)					II (n= 16)	
LAD		LCX	RCA		LAD		LCX	RCA
no stenosis                   3 (21 °/	o)	2 (14 %)	3 (21	%)	3 (19 °/	Xo)	6 (38 %)	5 (31 %)
stenosis <50                4 (29 °/	o)	7 (50 %)	0(0'	%)	2 (13 °/	Xo)	4 (25 %)	4 (25 %)
stenosis 51-70% 2(14°/	o)	2 (14 %)	3 (21	%)	1 (6 %	.)	1 (6 %)	2 (13 %)
stenosis 71-99% 3(21°/	o)	1 (7 %)	3 (21 %)		4 (25 °/	Xo)	3 (19 %)	2 (13 %)
totally occluded            2 (14 °/	o)	2 (14 %)	5 (36	%)	6 (38 °/	Xo)	2 (13 %)	3 (19 %)
The values are expressed as number of arteries (%). LAD = left anterior descending artery; LCX = left circumflex; RCA = right coronary artery.
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Table 3. Changes of Sa value after follow-up in different groups of LV walls at rest and at the maximal load.
Cohort
I (n = 14)
At rest
II (n = 16)
At the maximal load I (n = 14) II (n ■■
16)
Wall group A B C D E
All (global function)
-1.56±0.93 1.29±0.63 -0.64±0.69 -0.09±0.86 0.37±0.60 0.23±0.36
-0.86±0.38
0.62±0.58
0.14±0.88
-0.10±0.30
-1.76±0.40*
-0.53±0.22
0.16±0.84 3.83Ü.13 -0.42il.02 -2.82il.19 1.70Ü.43 1.26i0.65
-2.67i0.87* 0.56Ü.05 -0.58+1.92 -2.29i0.86 0.02i0.78 -1.25i0.45*
The values are expressed as the mean supplied by standard error (in parentheses). Sa = peak systolic velocity of mitral annulus; LV = left ventricle. Wall groups: A- walls supplied by nonstenotic artery; B- walls supplied by artery with coronary stenosis < 50 %; C- walls supplied by artery with stenosis 51-70 %; D- walls with stenosis of supplying artery 71-99 %; and E- walls with totally occluded supplying artery. * p<0.05 between cohorts.
The changes of Sa value after follow-up in different groups of LV walls are shown in Table 3. In global systolic function, the values of Sa glob in cohort I were improved by 0.23i0.36 as compared with baseline values at rest, and by 1.26i0.65 cm/s at the maximal load, while the values of Sa glob in cohort II were diminished by 0.53i0.22 (p=NS), and by 1.25±0.45 cm/s (p<0.05), respectively.
Concerning the resting regional function, the only significant difference between cohorts in follow-up changes was found in walls E: 0.37i0.60 versus -1.76i0.40 cm/s (p<0.05). At the maximal load, the significant difference was found only in walls A (0.16i0.84 versus -2.67i0.87 cm/s; p O.05). Sa changes in other walls was not significant.
Discussion
Effect of CR on global LV systolic function
The present investigation suggests that long-term exercise training can improve LV systolic function in patients with coronary artery disease. Previous works have shown variable results in relation to influence of CR on the LV function (Belardinelli et al. 1996, Hambrecht et al. 2000, Giannuzzi et al. 2003, Klecha et al. 2007). The failure to assess changes in LVEF in some studies may have several reasons. It may be the result of different study populations, kind and intensity of the training programs or the measurement techniques (Webb-Peploe et al. 2000). Only patients with chronic heart failure or after myocardial infarction with moderate-to-severe LV dysfunction were included in the majority of studies assessing the influence of CR on LV function. In
comparison with them, our patients had only slight depression of LVEF and not all of them underwent clinical myocardial infarction.
The intensity and duration of CR necessary for LV function improvement have not yet been sufficiently evaluated. In the analysis in the work of Piepoli (2004) the data suggested that only long-term duration over 28 weeks of CR may be required to reach benefits in mortality and adverse events rates. The antiremodelling effect of training with a trend towards improvement of LV functional parameters was found after 6-month training in the work of Klecha et al. (2007). On the other hand, the work of Hambrecht (2000) demonstrated that an intense CR program can improve resting LVEF in 2 weeks. In our work, just 1-year CR improved LV systolic function, while the 3-month training did not provide the sustained long-term functional improvement.
The utilization of LVEF, as an evaluated parameter of LV function, could be one of the main factor contributing to the failure of some previous studies to shown the effect of CR. LVEF is a load-dependent parameter and is very rough to assess expected slight changes of LV function. EF evaluated by 2D echocardiography is strongly dependent on image quality and endocardial border delineation. In contrast, TDI is robust, reproducible and may be more sensitive marker of LV longitudinal systolic function and it is feasible even in poor echocardiographic windows. Hence, TDI allows evaluation of even minor changes in LV function that are not detectable by 2D assessment. In several published data, TDI has been applied to stress echocardiography in order to overcome the limitation of only visual analysis (Cain et al. 2001, Fathi et al. 2001, Garcia et al. 2006,
2011
The Effect of Physical Activity on the Left Ventricle Systolic Function 873
Bougault et al. 2008, Duzenli et al. 2008).
Effect of CR on regional LV systolic function
This present study is the first trial to evaluate the effect of CR on regional LV systolic function in relation to blood supply of individual LV walls. TDI was chosen for this purpose, because it permits quantification of regional longitudinal myocardial systolic velocities with a high temporal resolution and can overcome the limitation in the subjective echocardiographic evaluation of regional ventricular function (Reuss et al. 2005). Our data showed that the effect of CR on LV systolic function is caused mainly through the improvement of contractility in walls supplied by a totally occluded coronary artery. The effect of physical training and LV global and regional function was assessed by TDI also in the study of Deljanin-Ilic et al. (2007). After 6 months, LV EF increased significantly as well as the regional systolic myocardial function at the previously infarcted wall only in the training group.
Mechanisms of this training effect have not yet been established. The most likely explanation is the combination of beneficial changes in ventricular wall tension and favorable adaptation in the coronary circulation. The physical training may have beneficial effect on changes in autonomic balance toward a vagal predominance, which could limit the deleterious effects of sympathetic hyperactivity on the LV remodeling and function, analogously to treatment with beta blockers.
In patients with stable coronary artery disease, augmented delivery of blood to ischemic myocardium has been shown to take place in response to physical training (Hambrecht 2004). The beneficial effect of CR on morbidity and mortality has been attributed to the growth of collateral vessels between healthy and under-perfused myocardial regions (Shephard and Balady 1999). This theory was documented for example by work of Zbinden et al. (2007) where beneficial dose-response effect of 3-month endurance exercise training on collaterals has been found. However, other human studies have failed to document consistently the formation of collaterals. The main reason for different results may have been the lack of sensitivity of angiography to detect small coronary collaterals. The collateral growth and other coronary vascular changes may improve function of chronically hypoperfused myocardium.
Furthermore, CR has been shown to favourably affect blood flow rheology, thereby possible improving of myocardial perfusion. The improvement in myocardial blood flow to the infarcted area may lead to recovery of
both global and regional LV function (Schuler et al. 1992). Although our study cannot elucidate the possible mechanism of regional functional improvement, we speculate, that combination of autonomic system changes and especially the development of collaterals may have facilitated partial functional recovery of dysfunctional but viable myocardial regions supplied by a totally occluded coronary artery.
Study limitations
Our study had several limitations. The study was retrospective, not randomized. The interpretations of results could be limited by a relatively small sample size in both cohorts. Also our study can be influenced by the difference between the number of men and women and the difference between patients age in both cohorts, because age and gender are determining factors for training effects - smaller improvements of women as well as a negative relation between age and improvement in exercise performance is known (Vanhees et al. 2004).
Another limitation is the fact, that the 9-months training of cohort II have been performed as an outpatient individual training without any supervision. The information about frequency and intensity has been obtained only from patient's anamnesis during their regular visits in outpatient department. However, very different types of training programmes are described in literature and in some studies, a home-based CR had no significant differences in the main outcomes compared with the centre-based programme (Jolly et al. 2009) or an outpatient CR led to further improvement of followed parameters in comparison to supervised CR in a hospital (Benzer et al. 2007).
Certainly, further research is required, especially in order to optimize the effectiveness of CR programs and to better understand the mechanisms responsible for the improvements related to CR training.
Conclusion
In our study, patients with regular 12-month physical activity improved their global left ventricle systolic function mainly due to improvement of contractility in walls supplied by a totally occluded coronary artery.
Conflict of Interest
There is no conflict of interest.
874 Panovsky et al.
Vol. 60
Acknowledgements
The work was supported by European Regional Development Fund - Project FNUSA-ICRC (No. CZ. 1.05/1.1.00/02.0123), by a grant of the Ministry of
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BENZER W, PLATTER M, OLDRIDGE NB, SCHWANN H, MACHREICH K, KULLICH W, MAYR K, PHILIPPI A, GASSNER A, DÖRLER J, HÖFER S: Short-term patient-reported outcomes after different exercise-based cardiac rehabilitation programmes. Eur J Cardiovasc Prev Rehabil 14: 441-447, 2007.
BOUGAULT V, NOTTIN S, DOUCENDE G, OBERT P: Tissue Doppler imaging reproducibility during exercise. IntJ Sports Med 29: 395-400, 2008.
CAIN P, MARWICK TH, CASE C, BAGLIN T, DART J, SHORT L, OLSTAD B: Assessment of regional long-axis function during dobutamine echocardiography. Clin Sei 100: 423-432, 2001.
DELJANIN-ILIC M, ILIC S, STOICKOV V: Effects of continuous physical training on exercise tolerance and left ventricular myocardial function in patients with heart failure. SrpArh CelokLek 135: 516-520, 2007.
DUBACH P, MYERS J, DZIEKAN G, GOEBBELS U, REINHART W, VOGT P, RATTI R, MULLER P, MIETTUNEN R, BUSER P: Effect of exercise training on myocardial remodeling in patients with reduced left ventricular function after myocardial infarction. Circulation 95: 2060-2067, 1997.
DUZENLI MA, ÖZDEMIR K, AYGUL N, ALTUNKESER BB, ZENGIN K, SIZER M: Relationship between systolic myocardial velocity obtained by tissue doppler imaging and left ventricular ejection fraction: Systolic myocardial velocity predicts the degree of left ventricular dysfunction in heart failure. Echocardiography 25: 856-863, 2008.
FATHI R, CAIN P, NAKATANI S, YU HC, MARWICK TH: Effect of tissue Doppler on the accuracy of novice and expert interpreters of dobutamine echocardiography. Am J Cardiol 88: 400-405, 2001.
GARCIA EH, PERNA ER, FARIAS EF, OBREGON RO, MACIN SM, PARRAS JI, AGUERO MA, MORATORIO DA, PITZUS AE, TASSANO EA, RODRIGUEZ L: Reduced systolic performance by tissue Doppler in patients with preserved and abnormal ejection fraction: New insights in chronic heart failure. IntJ Cardiol 108: 181-188, 2006.
GIANNUZZI P, TEMPORELLI PL, CORRA U, GATTONE M, GIORDANO A, TAVAZZI L: Attenuation of
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ORIGINAL HESiAR-H
ASSESSMENT OF THE LEFT VENTRICLE DIASTOLIC FUNCTION IN A GROUP OF PATIENTS WITH CHRONIC ISCHAEMIC HEART DISEASE AND REGULAR PHYSICAL ACTIVITY
Kulcla P.1, Panovsky R.1, Jantar R.', Kind V. \ Varnay F. ^Chkidilova V.', Dobiak P.', Jancik J.:, Siegelova J.'
1 First Department of Internal Medicine/Cardtoangiology, St Anne's Faculty Hospital, Masaryk University ICFtC, Brno, Czech Republic
3 Department of Functional Diagnostics and Re habitation, St. Anne's Faculty Hospital, Masaryk University, Brno, Czech Republic
ABSTftACT
Received after revision August 2010
KEYWORDS
Aerobi: training
Left ventricle diastolic function
Chronic isrhaemic heart disease
E
CORRESPONDING AUTHOR Kukla P.
Gorkého 11D6/21, 767 u I Křemení Czech Republic
Aim
Assessment of the left ventricle diastolic function In a group of patients with stable coronary artery disease and regular physical training.
Methods
The study induded thirty patients with stable coronary artery disease. Every patient had participated in the conducted l-mo:h physical training in Department of Functional Diagnostic and Rehabilitation St Anna Hospital. After one year the patients were retrospectively divided into two cohorts according to their physical activity.The patients in cohort C Iconsisting of 14 patients) continued in aerobic physical training after the end Df the rehabilitation programme.The patients in cohort H (consisting of IS patients) had stopped their training after finishing (he conducted programme in St. Anne's Faculty Hospital.
The peak diastolic velocities of myocardial notion were measured at i ndividual LV walls: septum, lateral, anterior, and inferior walls. In addition. Id determine global LV diastolic function, the rbur-site mean diastolic velocity was calculated LEa glob, Ei'Aa glob). The velocities were evaluated at rest and at the maximal load.
According to blood supply, left ventricular walls were divided into five groups: 0 - walls supplied by non-stenotic artery; ; - walls supplied by a rtery with coronary stenosis s So lit; 2 -walls supplied by artery with stenosis 51-75%; 3 - walls with =:encsis of supplying artery 71-994 - walls with totally occluded supplying artery. For every patient the difference between the values Ea and Ea/Aa for each wall at the end of the study and the values at the beginning of the study was assessed. The values of the partkoila r walls were divided into
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Table 1
Population under study
	Cohort C	cohort N	
flge (years}	6O±10	&3tE	
Number of arteries wi'h stenosis:: 70 %	1	l.Bll.2	
DM	4)%	19%	
Ml	50 K	63%	
Hypertension		IQTJ*	
HLPP		91%	
ef :-.!	5D.a±10Jä	4S.6l12.4	
Male/female	13H	9/7	4
Explanatory notes: values are shown as average t standard deviation; EF: LV ejection fraction; Ml: myocard ial infarcriori; DM: diabetes mellitus;HLPP hyperlipcprateinaemia:* pcO.DS between cohorts
Tab a
Changes of the value-1 haracterlstlts -of d laBtollt funcdon
	rest						stress					
	Ea			Ea/Aa			Ea			Ea/A;		
Cohort	C	N		C	N		C	N		C	N	
0	-TJuHaJjQB	-i.+i±i£e		-Ojniuo.14	-0.1D10.24		-Q.44±153	-1J03±2,24		-D.14D0J5	OJtHlflJ?	
1	0.2712.93	-0261137		-OJ05U0.23	0.D3.1O.12		1J51L7B	2JJ51337		0.0110,17	0.1 lDOJO	
2		-1.6413.69		o ■ 7.	-o.imo.M		D.5H2.S7	DJ6214.97		OO010-2J	0.13U0.43	
3	OJ513.H	-0j66±1J1		O.OJrO.34	0.14x030		-O.D4±4.S6	-D.43i3.00		DO 91037	0J5±0.S7	
4	-D.4fl±2-77	-D.77±2JB		-OJ06±0.3J	OD3±0.1S		*Jfl±3.65	-0.68:12.74	w	i :9z;.:9	-D.03lO.24	
Global function	0 ;-5z2.?i	-O.£9±2.01	4	-OJ0210.26	O.DItDJfi		U7±3.75	-0.1J±3JO	w	0061036	DjOfttflJB	
Eipianatory notes: values are shown as average t standard deviation;* ptO.DS between cohorts; rest = investigation at rest; stress - investigation d uring maximal load; C = cohort L; H = cohort N; q no ups 0,1,2,3,4 = acccrdi ng to blood supply; global function = Ea global or Ea/Aa g bba I as the average of all LV walls
5 grou ps according to blood supply llhese 5 groups were creased using coronarrjgraphyr.
The-differences of these values at rest a nd stress between both cohorts of patients were statistically processed using an unpaired '-test; p^fl.05 was considered statistically srrjnifcan:. Results: In global diastolic function, the values of Ea global in cohort C were improved by Dj05±Z34 rm/s at Test, and by 1.3713.75- cm/s at maximal load, while the values of Ea global
in coho rt M were d imi nished by -0.Bftri.oi cnVs (p^OjOi versus cohort Cj, and by-0.13i320cm/'s; Lp<:0.D5 versus cohort C.l atdiaffiimal load.
The most important benefit with d iastolicf unction was found in group 4 (groups with totally occluded coronary artery). The values of Ea in cohort C were improved by 4 J4±3u65 cm/s, while the values in cohort N were diminished by -Oj6Si2.74 cm/s; ip iDu(H versus cohort C) atmarimal load.
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The results Df the other Ea values were not significant. The Ea/Aa values in group + in cohort C were improved by ■I-2910.39-en's at maximal load, while the values of Ea/Aa in cohort N were diminished by -O.OJtO.34 cnf's; ip■--.0.05 versus cohort Q at maximal load. The results of the Dther Ea; Aa values were not significant. Conclusion
Our patients with 12 months' training improved their global dia =:al ic function. The most important benefit was found in walls supplied try occluded artery.
ABBREVIATIONS USED
TDI - tissueOoppler imaging LV - left ventride
5a- systolic phase of cardiac cyde
5a- peak of isovolumic contraction
Ea - fast filling diastolic phase
Aa -atrium contraction end of diastole phase
EF LV-LV ejection fraction
Ml - myocardial infarction
DM - diabetes mellitus
INTBODJCTION
The effect of regular physical activity on the cardiovascular system and myocardial function are global. The risk factors are reduced (by changi ng the way of life, strength of Ihews). heart rate and blood pressure are decreased, the peripheral venDustone is im proved, and a positive influence-an the left ventricle tlV:- is probable.
Tissue Doppler imaging |TE>U is an echooardiog raphic method using the Doppler effect Using this method it is possible to measure the velocity of myocardial motion in both systolic and diastolic phases of cardiac cycle [I]. The difference between the classic Doppler sonography and TEH is in using special filters that eliminate signals which are repulsed back by blood cells, and reversibly intensify signals that are repulsed by the rryocard iurr (these signals are marked with high amplitude and low frequencyj. There are two types of TDI: pulsed TDI and colour TDi Using the pulsed TEX we get the characteristic curve, which consists of three main waves iFtqure r,\ The positive Sa wave represents the systolic phase of the cardiac cycle.This wave is frequently two-phased with a first slim peak of isovolumic contraction |Sa')and a second, wider wave of LY ejection.The fust negative wave after the Sa wave is called Ea; it represents fast filling of the ventricle in the diastolic phase of the cardiac cycle. The second negative wave (AaJ grows from atrial contraction at the end of the diastolic phase of the cardiac
fig.nt 1 ChJvrrtutf Iftk CurVi of pJrtd TDI.
Figure I
The characteristic curve of pulse TDI
Sa - systolic phase of cardiac cyde
Sa'-peat of isovolumic contraction
Ea - fast filling diastolic phase
Aa -atrium contraction end Df diastolic phase
cycle. The * a wave is missing in the case of atrial fibrillation \2\. During exercise rest" the waves Ea and Aa are often fusing |3] caused to the faster heart rate
By measuring the amplitude of these single waves, the maximal velocity of each myocardial segment d unng the card iac cycle can be evaluated. In myocardial pathologies the velocity values for each segment and also the overall value of the ventricle function are changed. The velocity of all 17 myocardial segments can be measured [4]. Physiologically, the velocities are getting higher in segments from the apex toward the heart base. TDI ca n be used for the evaluation of both regional and global function of both ventricles tooth systolic and diastolic ventricle function). We can peeve myocardial ischaemia, and reversible and non-reversible myocardial dysfunction [2|. During ischaemia the maximal Sa and Ea velocities a re red uced. The change of Aa is not sign iiicant, so the Ea/Aa ratio in the ischaemic area is getting down [1]. The purpose of this study was tD assess the effec: of aerobic train ing on the left ventricular diastol n function in a grou p of patients with chronic ischaemic heart disease.
MATERIALS AND METHODS
The study included thirty patients with stable coronary artery disease. These patients were retrospectively divided into two cohorts with different reg ular physical train ing. The cohort C consisted of 14 patients. These patients had participated in a conducted J-ncn'h ohysca training a:; he Department of Functional Diagnostics and Rehabilitation of St. Annes' Faculty Hospital, and after the 3 months they canli nued with indi-vid ual training far 9 more months. The regula r physica I training consisted of J phases in 60 minutes 3 times a week. The
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first phase of the (raining is called warrr ing-up and last= far ten minutes.The second phase is an aerobic period and last= for 35 rranutjetThis phase consists of power training and riding a bicycle ergameter. The third phase is a relaxation phase and lasts far 15 minutes, "he S-month individual training consists of regular physical activity performed for one hour at least three times a week. As a regular physical activity the patients chose Dne of the following sports: riding a bicycle ergometer, cyd ing, or swimming. The cohort N consisted of 16 patients. These patients stopped the training after having finished with the conducted programme. The cohort's characteristics a re shown in Table J.
Atthe beginning of the srudy coronarography was performed. According to blood supply, the left ventricular walls were divided into five grou ps: 0 - walls, supplied by non-stenotk artery; 1 - walls supplied by artery with coronary stenosis s 2 - walls supplied by artery with stenosis 51-7D Wf 3 -walls with stenosis of supplyi ng artery 71 -99 ft; 4 - walls with totally occluded supplying artery.
Rest and stress dobutamine/atropine echocardiography was performed in all patients before the training programme and one year later. Three days before the rest/stress, dobutamine echocard iography the beta blockers were discDntin ued. Using the commercially available equipment Scn?= i SuO (Hewlett-Packard, US) with a 2.5 MHz transducer, echocardiography was performed in standard views - parasternal long axis, parasternal short axis (level of papillary muscles}, apical 4-and 2-chamber views.The peak diastolic velocities of myocardial motion were measured at individual LV walls: septum lateral, anterior, and inferior walls. In addition, to determine the g kobal LVdiastolic function, thefau r-site average d iastDlic velocity was calculated |Ea glob, Ea/'Aa glob). The velocities were evaluated at rest and at the maximal load. For every patient the difference between the values Ea, Ear' Aaforeach wallatthe end of the study and the values at the beginning of the study was assessed. The values of the particular walls were divided into 5 groups according to blood supply rthese 5 groups were created using coronarography:. Thedifferences of these values during rest ard maximal stress between both cohorts of patients were statistically processed using an unpaired :-tes:, p^I.05. was considered statistically significant
BESUITi
The results are shown in Table 2.
In the gbbal diastolic function, the values of Ea global in cohort C were improved by n.Q5±i_M em's at rest, and by 1 J7±3.75 onVs at maximal load, while the va lues of Ea global in cohort H were diminished by -0.S9t3.Dl em's (p-rO.DS
versus cohort Q, ind £>■ C.12 -5.;-: :n-'=: :p'.;.Of versLE cohort C|at maximal load.
ThemDst important benefittothe diastolicfunctionwas found
in group 4 (groups with totally occluded coronary artery). The
values of Ea in cohort C were improved by 1.24i3u6S tmfs,
while the val ues in cohort H were diminished by -Qj66±2.74
:m/s; IptDuas versus cohort Q atmajdmal load.
The results of the Ea values from other walls were not
significant
The Eav'Aa values in group 4 in cohort C were improved by D29iOJ59 cm/s at maximal load, while tfie values of Ea/Aa in cohort N were diminished by-O.OJtO^cnVsjJp^u.DS versus cohort Q at maximal load.
The changes of the results of the other Ea'Aa values were no-: s gnirka-t
In cohort C, as the stress test was performed, 12 of 14 patients had a stress-induced kinetic disorder \2 patients had negative stress tests). In cohort H, as the stress test was performed, 12 of Inpatients had a stress-ind uced kinetic disorder (4 patients had negative stress tests, but 2 of them had the typical stress-performed chest pain without objective kinetic disorders;-.
DISCUSSION
In our wo rk we used TCI to assess c hanges of the LV diastolic function.In patients with chronicischaenic heart diseasewe performed the maximal stress test
The regular physical activity has a positive influence on the diastolic function of (he left ventricle. In our study we found an improvement of the global diastole 1unction during the rest and also d uring the maximal load. However, our results are not the same as the results i n the Yu CM study [5], which proved no progression Df diastolic dysfunction in a group of physically active patienLs.
We have to be cautious in our conclusion of diastolic function im provement, beca use the age average in both cohorts is not the same. The diastolic function is known to worsen over the age [6|, and the patients in cohort N were significantly older than those in cohort C. And there was also a difference between the substitution of men and women in both cohorts Nowadays the influence of regular physical training on the progression of age-caused diastolic dys-function is not clear. Same studies proved the influence of regular physical traini ng [7\- si n ila rly in the study of Arbab-Zadeh et al. [a], in which sedentary seniors versus master athletes were compared. The concl us ion d rawn there was that prolonged endurance training preserves ventricular compliance with aging and may help to prevent heart failure in the elderly.
However, the results of some studies a re different; th us, in the study of Hottin etal. [9], in which master athletes with long-
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ASSESSMENTCf THE LEFT VENTRICLE DIASTOLIC FUNCTCN..
term endurance training were compared with sedentary seniors and young adult nun. The authors concluded that endurance training doe; no: prevent fron the LV diastolic dysfunction.
STUDY LIMITATIONS
Our study has several limitations The interpretations rjf the result may be limited by a relatively small number of patients in tvjTh cohorts* Also, our study can be influenced by the difference between the number-of men and women and the difference between the patients' age in both cohorts.
ACKNOWLEDGEMENTS
The wort was supported bye grant of the Ministry of Education Df the Czech Republic (MSM, No. »21633+02).
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6. Redone MD, Castro I, Hatem D, ef a I. Changes in the parameters of left ventricular diastolic function according :c age on tissue Doppler imaging. Arquivos Erasileirosde Cardiolcala 2004, BJ:+51-469.
7. Forman DE, Manning WJ, Häuser R, et al. Enhanced left ventricular diastolic filling assodated with long-tern endurance training. J Gerontol 1992;47: M56-M5B.
a. Arbab-Zadeh A. Dijk E, Prasad A, et al. Effect of aging and physical activity on left ventricular compliance. Circulation 2004; 1 1 ft 1799-1KB.
9. Nottin 5, HJguyen LDrTerbah M, Obert P. Long-term endu r-ance training does not prevent the age-related decrease in the left ventricular relaxation properties. Acta Physiol
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Acta Cardiol 201 3; 68(6): 575-581      doi: 10.2143/AC.68.6.8000004
575
The prognostic effect of different types of cardiac rehabilitation in patients with coronary artery disease
Roman PANOVSKÝ1, MD, PhD; Pavel KUKLA1, MD; Jiří JANČÍK2, MD, PhD; Jaroslav MELUZÍN1, MD, PhD; Petr DOBŠÁK2, MD, PhD; Vladimír KINCL1, MD, PhD; Adam SVOBODNÍK3, MSc, PhD
'First Dept. of Internal Medicine - Cardioangiology, International Clinical Research Center - ICRC, St. Anne's Hospital, Masaryk University, Brno, Czech Republic; 2Dept. of Functional Diagnostic and Rehabilitation, St. Anne's Hospital, Masaryk University, Brno, Czech Republic; 'Dept. of Clinical Development and Technology Transfer, International Clinical Research Center - ICRC, St. Anne's Hospital, Brno, Czech Republic
Aim The purpose of this study was to access and compare the prognostic effects of different types of cardiac rehabilitation (CR) in patients with chronic coronary artery disease.
Methods One hundred fifty-two patients were retrospectively divided into 4 groups according to their adherence to physical activity recommendations. Patients in groups 1 and 2 participated in the guided 3-month exercise programme. Patients in group 1 then continued with individual exercise training, while patients in the group 2 stopped exercising after finishing the guide exercise programme. Patients in group 3 participated only in individual exercise training throughout the whole follow-up period, and patients in group 4 declined all exercise recommendations and did not exercise. The prognostic outcome of different types of cardiac rehabilitation was compared among the groups. In addition, patients who participated in individual exercise training according to recommendations (cohort IT+) were compared with patients who declined these activities (cohort IT).
Results During a median follow-up of 94 months, 33 deaths occurred; 17 cardiovascular and 16 non-cardiac deaths. A Kaplan-Meier survival analysis demonstrated significantly better survival rates for patients who followed a long-term aerobic exercise training (IT+) than for those who did not participate or who had only a short-term exercise programme (IT) (P = 0.009).
Conclusion   In our study, long-term exercise training had a higher impact on patient survival than short-term guided CR. Key WO rd S  coronary artery disease - cardiac rehabilitation - prognosis - cardiovascular risk
INTRODUCTION
The beneficial effects of cardiac rehabilitation (CR) on secondary prevention of coronary artery disease are well-established and regular physical activity, including exercise, is recommended by many guidelines13. The major objective benefits are an increased exercise capacity4 and reduced rates of cardiac events and
Address for correspondence:
Roman Panovský, M.D., Ph.D., First Department of Internal Medicine - Cardioangiology, International Clinical Research Center - ICRC, St. Anne's Hospital, Masaryk University, Pekařská 53,656 91 Brno, Czech Republic. E-mail: panovsky@fnusa.cz
Received 10 October 2012; revision accepted for publication 1 5 July 2013.
mortality5. In addition, the beneficial effects on cardiovascular risk factors - blood pressure, lipid levels, glucose metabolism, body weight, as well as on the endothelial function and psychological well-being -have also been proven6.
The structure and intensity of CR programmes vary widely among different countries and centres7. However, in spite of their benefits and guideline recommendations, only a minority of eligible patients participated in and completed these programmes. Alternative home-based CR activities might help to solve the problems of the poor uptake and adherence of outpatients or inpatients to centre-based CR programmes. Furthermore, the physical activity behaviour of patients, especially their participation in walking and vigorous activities, was found to be inversely associated with the use of antidiabetic, antihypertensive, and lipid-lowering drugs8'9.
576 R. Panovský et al.
The purpose of this study was to assess and compare the prognostic effects of different types of aerobic exercise programmes in patients with chronic stable coronary artery disease.
PATIENTS AND METHODS
Patient population and study protocol
The study comprised 152 consecutive patients with stable coronary artery disease with at least one coronary artery stenosis of more than 50% in the luminal diameter (proved by the coronary angiogram performed before the study). The exclusion criteria were: (1) coronary artery bypass graft or coronary intervention less than 3 months before inclusion; (2) known need for future coronary revascularization; (3) unstable patients; (4) haemodynamically important valve disease; (5) non-cardiac disease adversely affecting prognosis; and (6) non-cardiac disease seriously limiting the participation in cardiac exercise programmes.
Participation in the supervised outpatient cardiac rehabilitation and individual aerobic exercise training programmes were recommended to all patients. After the follow-up, the patients were retrospectively divided into 4 groups according to their acceptance of the exercise recommendation. Patients in groups 1 and 2 participated in the guided 3-month physical exercise programme. Patients in group 1 continued to exercise individually; patients in the group 2 stopped their exercise after finishing the guided programme. Patients in group 3 participated only in an individual exercise training programme throughout the follow-up period, and patients in group 4 declined all exercise recommendations and did not exercise. For further evaluation of the effect of different types of aerobic exercise, patients who attended the supervised cardiac rehabilitation (cohort CR+, comprising patients of groups 1 and 2) were compared with patients who did not (cohort CR-, comprising patients of groups 3 and 4). Similarly, patients who participated in the individual training programme in accordance with the recommendation (cohort IT+, comprising patients of groups 1 and 3) were compared with patients who declined these activities (cohort IT-, comprising patients of groups 2 and 4).
During the follow-up period, all patients were medically treated according to the evidence-based medicine. Significant effort was spent also on motivating the patients toward non-pharmacological treatment of risk factors, including not only physical exercise, but also smoking cessation, dietary and weight recommendations. Mortality and major adverse cardiac events (MACE) were assessed during follow-up visits. The primary end point was all-cause mortality; the
secondary end points were a composite of MACE, including myocardial infarction, unstable angina pectoris, coronary revascularization, and hospitalization for heart failure.
The study was in accordance with the Declaration of Helsinki (2000) of the World Medical Association, and was approved by the institutional ethics committee. Written consent was obtained from each patient.
Physical exercise
The guided programme offered 3 months of 3 times weekly sessions. Each session lasted for 60 minutes and consisted of 3 different phases: 10 minutes of warm-up, 20 minutes of aerobic exercise on a bicycle ergometer with a load intensity at the level of the anaerobic threshold, 20 minutes of resistance training on the combined training machine, and 10 minutes of relaxation.
Aerobic exercise intensity was individually prescribed according to initially performed symptom-limited spiro-ergometry. The protocol with intensified workload up to the symptom- limited maximum was used starting on 40W, increasing by 20W each 2 minutes. The respiratory gases were analysed under physical exercise (Blood Gas Analyser, MedGraphics, USA). The anaerobic threshold value for prescribing suitable load intensity was determined according to the corresponding value of heart rate and degrees of the Borg scale of subjective perception of load intensity.
The individual exercise training programme consisted of regular physical activity performed for a minimum of 1 hour at least 3 times per week. As a regular physical activity, patients were asked to choose cycling, riding a bicycle-ergometer or swimming.
Statistical analysis
For descriptive purposes, basic summary statistics such as mean, median, standard deviation, minimum and maximum were assessed for continuous data analysis, and absolute and relative frequencies for binary and categorical data. Groups were compared in continuous parameters by the ANOVA or Kruskal-Wallis ANOVA test if appropriate (the Kolmogorov-Smirnov test was used to analyse distribution of the data). Distribution of binary and categorical data between the groups was tested by a chi-square test.
Survival analysis (overall survival and cardiovascular survival) was performed using the Kaplan-Meier method, and groups were compared by log-rank test or by chi-square test. Cox proportional hazard regression model was used for multivariate analysis. All data were analysed at the significance level of a = 0.05, and all the tests were two-tailed.
The prognostic effect of cardiac rehabilitation 577
RESULTS
Baseline patient characteristics are presented in tables 1 and 2. Most parameters were similar in all four groups, but there were significant differences among the groups in age, sex, and in the number of diabetic and dyslipidaemic patients. Medical treatment before the study and after follow-up is shown in tables 3 and 4. No statistically significant differences were found among the 4 groups.
During a median follow-up of 94 months (range 2-158) after inclusion, there were 33 deaths (17 cardiovascular and 16 non-cardiac deaths). The Kaplan-Meier survival curve for all four groups is shown in figure 1. Patients in group 3 had a statistically better survival than
group 2 (P = 0.042) and group 4 (P = 0.041). The survival between other groups did not differ statistically. The result of an overall test comparing all patient groups bordered on statistical significance (P = 0.067). No significant differences in survival were found between cohorts CR+ and CR- (P= 0.948). However, patients in cohort IT + had longer survival rates than cohort IT-CP = 0.009) (figure 2). Multivariate Cox regression analysis including baseline covariates (sex, age, diabetes mellitus, and dyslipidaemia) revealed group as an independent factor for survival on the borderline of statistical significance (P = 0.057).
The secondary end points are shown in table 5. The incidence of each of unstable angina pectoris, coronary revascularization, and hospitalization for heart failure
Group 4 P value
(n = 38)
Table 1   Study groups characteristics: medical history
Parameter	Group 1	Group 2
	(n = 32)	(n = 60)
Age (years)
Men
BMI
LVEF(%)
No of stenotic arteries (> 70%) Coronary revascularization DM
Hypertension Dyslipidaemia Smoking
71.5 ±10.0 32 (100.0%) 27.3 ±3.3
48.6 ±8.8 1.5 ±0.7
19(59.4%) 5(15.6%) 31 (96.9%) 25 (78.1%) 8 (25.0%)
71.8 ±8.8 43(71.7%)
28.3 ± 3.0
46.9 ±10.1 1.5 ±0.7
29 (48.3%) 19(31.7%) 58 (96.7%) 53 (88.3%) 8(13.3%)
63.8 ±10.3 20 (90.9%)
28.3 ± 3.0
49.5 ± 7.6 1.4 ±0.6 15(68.2%)
2(9.1%) 22 (100.0%) 22 (100.0%)
7(31.8%)
73.9 ±8.7 27(71.0%) 27.6 ±3.8 50.1 ±11.6 1.4 ±0.6 17(44.7%) 14(36.8%)
37 (97.4%)
38 (100.0%) 6(15.8%)
0.002*
< 0.001* 0.622 0.276 0.526 0.243 0.028* 0.727
< 0.001* 0.223
Values are expressed as the mean ± standard deviation or the number of subjects with the percentage in parentheses. BMI: body mass index, LVEF: left ventricular ejection fraction, DM: diabetes mellitus, *P < 0.05 between groups.
Table 2   Study cohort characteristics: medical history
Parameter	GroupCR+ (n = 92)	Group CR-(n = 60)	P value	Group IT+ (n = 54)	Group IT-(n = 98)	P value
Age (years)	71.7 ±9.1	70.2 ±10.4	0.392	68.4 ±10.7	72.6 ±8.7	0.007*
Men	75(81.5%)	47 (78.3%)	0.679	52 (96.3%)	70 (71.4%)	< 0.001*
BMI	27.9 ±3.2	27.9 ±3.5	0.867	27.7 ±3.2	28.0 ±3.3	0.585
LVEF(%)	47.5 ±9.7	49.9 ±10.2	0.091	48.9 ±8.3	48.1 ±10.8	0.519
No of stenotic arteries (> 70%)	1.5 ±0.7	1.4 ±0.6	0.148	1.4 ±0.7	1.5 ±0.7	0.868
Coronary revascularization	48 (52.2%)	32 (53.3%)	0.999	34 (63.0%)	46 (47.0%)	0.064
DM	24(26.1%)	16(26.7%)	0.999	7(13.0%)	33 (33.7%)	0.007*
Hypertension	89 (96.7%)	59 (98.3%)	0.999	53 (98.1%)	95 (96.9%)	0.999
Dyslipidaemia	78 (84.8%)	60 (100.0%)	< 0.001*	47 (87.0%)	91 (92.6%)	0.253
Smoking	16(17.4%)	13(21.7%)	0.532	15(27.8%)	14 (14.3%)	0.053
Values are expressed as the mean ± standard deviation or the number of subjects with the percentage in parentheses.
CR+: patients who participated in the guided exercise programme (comprising patients of groups 1 and 2), CR- = patients who declined to participate in the guided exercise programme (comprising patients of groups 3 and 4), IT+: patients who exercised individually (comprising patients of groups 1 and 3), IT-: patients who declined individual exercise (comprising patients of groups 2 and 4), BMI: body mass index, LVEF: left ventricular ejection fraction, DM: diabetes mellitus, *P < 0.05 between cohorts.
578 R. Panovsky et al.
Table 3   Study population characteristics: medical treatment before the study
Parameter	Group 1 (n = 32)				Group 3 (n = 22)	Group 4 (n = 38)	Pvalue
ASA	31 (96.9%)	57 (95.0%)			20 (90.9%)	35 (92.1%)	0.748
Beta-blockers	29 (90.6%)	58 (96.7%)			22 (100.0%)	35(92.1%)	0.236
ACEI	28 (87.5%)	50 (83.3%)			21 (95.5%)	28 (73.7%)	0.123
Sartans	0 (0.0%)		1 (1.7%)		1 (4.6%)	0 (0.0%)	0.393
Statins	23 (71.9%)	49(81.7%)			19(86.4%)	35 (92.1%)	0.146
Nitrates	24 (75.0%)	41 (68.3%)			13(59.1%)	29 (76.3%)	0.495
Values are expressed as the number of subjects with the percentage in parentheses. ASA: acetylsalicylic acid, ACEI: angiotensin-converting enzyme inhibitors..
Table 4   Study population characteristics: medical treatment at the end of the follow-up
Parameter	Group 1 (n = 32)	Group 2 (n = 60)				Group 4 (n = 38)	Pvalue
ASA	31 (96.9%)	58 (96.7%)	20 (90.9%)			36 (94.7%)	0.740
Beta-blockers	30 (93.8%)	58 (96.7%)	22 (100.0%)			35 (92.1%)	0.351
ACEI	21 (65.6%)	45 (75.0%)	19(86.4%)			25 (65.8%)	0.243
Sartans	2 (6.3%)	8(13.3%)		4(18.2%)		5(13.2%)	0.572
Statins	28 (87.5%)	54 (90.0%)	20 (90.9%)			35 (92.1%)	0.935
Nitrates	18(56.3%)	39 (65.0%)	13(59.1%)			30 (79.0%)	0.182
Values are expressed as the number of subjects with the percentage in parentheses. ASA: acetylsalicylic acid, ACEI: angiotensin-converting enzyme inhibitors.
Group 3 Group 1
Group 4 Group 2
N=152;p=0.067
N=152;p=0.009
0       20       40       60       80      100     120      140     160      180 200 Time [months]
Fig. 1   Kaplan-Meier curve for patient survival according to the physical activity - a comparison of 4 groups of patients
Group 1: patients participated in the supervised 3-month physica exercise programme and continued to exercise individually, group 2: oatients participated in the supervised 3-month physical training anc stopped exercise after that, group 3: patients only exercised individually throughout the whole follow-up period, group 4: patients declined all exercise recommendations and did not perform any exercise activities.
0       20       40       60       80      100     120      140     160     180 200 Time [months]
Fig. 2   Kaplan-Meier curve for patient survival according to the physical activity - a comparison of cohorts IT+and IT-.
Cohort IT+: patients who exercised individually, cohort IT-: patients who declined individual exercise.
The prognostic effect of cardiac rehabilitation 579
Table 5   Secondary end-points in groups and cohorts
	Group 1 (n = 32)	Group 2 (n = 60)	Group 3 (n = 22)	Group 4 (n = 38)	Among groups	Pvalue CR + vsCR-	IT + vs IT-
Ml	2 (6%)	5 (8%)	1 (5%)	7(18%)	0.249	0.275	0.149
UAP	6(19%)	22 (37%)	1 (5%)	8(21%)	0.008*	0.034*	0.018*
Revascularization	4(13%)	22 (37%)	3 (14%)	13(34%)	0.020*	0.855	0.002*
HF	0 (0%)	10(17%)	1 (5%)	4(11%)	0.017*	0.783	0.020*
Ml + UAP + revascularization + HF	8 (25%)	36 (60%)	4(18%)	21 (55%)	< 0.001*	0.368	< 0.001*
Values are expressed as the number of subjects with the percentage in parentheses.
CR+: patients who participated in the guided exercise programme (comprising patients of groups 1 and 2), CR-: patients who declined to participate in the supervised training (comprising patients of groups 3 and 4), IT+: patients who exercised individually (comprising patients of groups 1 and 3), IT-: patients who declined individual exercise (comprising patients of groups 2 and 4), Ml: myocardial infarction, UAP: unstable angina pectoris, HF: hospitalization for heart failure, *P < 0.05 among groups or between cohorts.
significantly differs among the groups and was higher in cohort IT + than cohort IT-. The composite secondary end point differed significantly among groups and between cohorts IT + and IT-, but no difference was found between cohorts CR+ and CR-.
DISCUSSION
The present study showed that an individual, long-term exercise programme has a higher impact on patient survival and rate of MACE than a short-term hospital-based CR programme. The potential beneficial effect of supervised exercise training is probably lost when the increased physical activity does not continue also after the guided programme is finished.
Physical activities clearly reduce the mortality of coronary artery disease patients10. While this is encouraging, the success of CR is largely dependent on patient adherence to exercise recommendations during both supervised exercise and self-managed exercise programmes. Unfortunately, the data show poor attendance and high dropout rates in guided CR. For example, Hansen et al.11 followed 119 patients with coronary artery disease 18 months after inpatient rehabilitation. They found very poor adherence (27%) to the recommended minimal physical activity level during the follow-up, low habitual physical activity in the total group, and progressively worsened cardiovascular disease risk profile of the patients. Similarly, Reid et al.12 found a significant decrease in habitual physical activity during long-term follow-up after hospital discharge in patients with coronary artery disease. The PIN study13 showed that the benefit of CR therapy following myocardial infarction or coronary revascularization is only partially maintained during the following year. The cardiac risk factors improved initially during CR, but deteriorated over the next 12 months.
The beneficial effect of cardiac rehabilitation is nowadays well recognized. However, it remains largely obscure, which characteristics of physical activity and exercise training are the most effective. In general, recommendations of exercise training programmes need to be tailored to the individual's exercise capacity and risk profile, with the aim to reach and maintain the individually highest fitness level possible14. A centre-based CR has several advantages, including better exercise supervision with possibilities for correcting the intensity and type of exercise as well as addressing safety issues. On the other hand, supervised CR could be more difficult for some patients to attend. Older age and high co-morbidity are strong predictors for non-attendance15. A valid alternative is home-based CR. These programmes are as effective as centre-based CR, but seem hopeful in targeting higher number of patients16 20. Our study confirmed that long-term individual CR is a very good alterative and could be even more effective than short-time guided exercise programmes.
In several studies, such as the HF-ACTION study21'22, exercise led only to a non-significant reduction in all-cause mortality or hospitalization. These studies failed to meet the previous expectations most probably due to non-uniform adherence to scheduled physical activity levels and a high percentage of exercise cross-over from the training group. In the HF-ACTION study, only approximately 40% of the patients in the exercise group reported weekly exercise volumes at or above the recommended level. Reasons for non-attendance usually varied - patients being "uninterested", illness, work scheduling, and transportation issues23. Patients are not easily convinced to permanently change their lifestyle habits. From the results of our study, it can be deduced that the initial patient enthusiasm for physical exercise and lifestyle changes and their resulting compliance with the exercise recommendations are the most important factors influencing the effect of exercise programmes.
580 R. Panovsky et al.
The results of the present study are certainly influenced by the fact that it is a non-randomized study and patients were divided into groups retrospectively according to their acceptance of the exercise recommendations. Patient motivation and willingness to exercise played an important role in the study, and most probably also in their lifestyle behaviour. Other potential prognostic factors, such as dietary behaviour, weight maintenance or loss, and medication compliance, were not assessed in this study. Nevertheless, all patients were treated according to the evidence-based medicine, and a significant effort was spent on motivating the patients toward non-pharmacological treatment of risk factors, including not only physical exercise, but also dietary and weight recommendations and smoking cessation.
The interpretations of results could be limited by the relatively small sample size of the groups. The study could also be influenced by the differences in age, gender, and diabetic and dyslipidaemic patients among the groups. Younger men showed the best compliance to individual aerobic exercise, and this certainly may have influenced the results of our study.
In this study, no other outcomes than mortality and mortality were assessed. It has been reported previously that the change in aerobic capacity after CR was related to mortality. According to the study of Vanhees et al, a 1% greater increase in peak oxygen uptake (VO ) after training was associated with a decrease in cardiovascular mortality of 2%. Peak V02, evaluated after a physical training programme, and its change in response to training were independent predictors for cardiovascular mortality in patients with coronary artery disease24. Physical training generally increases exercise capacity. The effect of our conducted 3-month training on functional capacity improvement is known and was published previously by our group25. However, patients in our trial had no aerobic capacity evaluation at the end of the follow-up. So that no direct comparison of the
impact different training programmes on aerobic capacity is possible.
Another limitation is the fact that the outpatient individual exercise was performed without any supervision. The information about frequency and intensity was obtained only from patient anamnesis during regular visits to the outpatient department. And finally, the cut-off point of individual exercise training at a minimum duration of 1 hour at least 3 times per week was defined for the group categorization. However, very different types of exercise programmes are described in the literature and in some studies a home-based CR had no significant differences from a guided centre-based CR programme in the main outcomes18, or an outpatient CR led to further improvements than an in-hospital supervised CR7. Certainly, further research is required, especially in order to optimize the effectiveness of CR programmes and to better understand the mechanisms responsible for the improvements related to CR exercise.
CONCLUSION
In our study, individual long-term exercise programmes had a higher impact on patient survival and rate of MACE than short-term hospital-based guided CR.
ACKNOWLEDGEMENTS
The work was supported by the European Regional Development Fund - Project FNUSA-ICRC (No. CZ. 1.05/ 1.1.00/02.0123).
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
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