MUNI MED PATOPHYSIOLOGY OF HEART FAILURE Lékařská fakulta Masarykovy univerzity Heart as a pump • Heart is a central organ of circulatory system • Heart ejects blood into systemic and pulmonary arteries • It removes blood from vena cava superior et inferior as well as from pulmonary arteries CO = SV (stroke volume) x f SV = EDV (enddiastolic volume) - ESV (endsystolic volume) EF [%] = SV/EDV Cardiac output has to match a venous return (4.CO in hypovolemic shock) Frank-Starling mechanism: stretching of muscular fibres increases the force of muscular contraction (up to a peak - force decreases with further stretching - Starling curve SV/EDV) Mechanisms leading into heart failure Extracardlac causes • 1^ preload • 1^ afterload Primary - cardiac causes • systolic dysfunction^ inotropy) • diastolic dysfunction (4/ lusitropy tachycardia) • bradycardia • 1^ preload and/or afterload (valvular disorders and shunts) Preload and afterload in a muscular fibre • Preload - force needed for keeping of muscle tension before the start of muscle shortening (isometric phase) • Afterload - force needed for isotonic contraction • Compared to skeletal muscle, cardiac muscle has much higher passive stretch force -during overstretching, the active force of contraction decreases, but the passive force increases - the resulting length-force curve is increasing • This also works in skeletal muscle, but the passive force is negligible in its working range, therefore, overstretching leads into the loss of total force Preload and afterload in the heart Law of Laplace for wall tension in a hollow sphere: a = Pxr , where: P....pressure inside the sphere r....inner radius of the sphere h....sphere wall thickness • Preload - wall tension (N.m 2 = Pa - force per area) before the systole 0 The main factor is venous return —> filling of cardiac ventricles • Afterload - increase in wall tension during the systole ° The main factor is a peripheral resistence, or pulmonary vascular resistence in the case of the right ventricle • Preload is higher in the right ventricle, afterload is higher in the left one 2h Muscular work of the heart - P-V diagram P-V diagram in the right ventricle P-V diagram and energy consumption PE: potential energy • Energy consumpton per a unit of myocardial P X7" SW: stroke work volume corresponds to wall stress (o = — : • MV02 ~ (PE + SW) x f see hypertrophy) P-V diagram during changes of preload or afterload Endsystolic P-curve Control I Preload § \ ' \ ^^^W Preload weis 100 200 IV Volume (ml) Enddiastolic P-V curve 200 O) I E E 2 100 3 M to CD n > 1 Afterload Limit of Frank-Starling mechanism (active muscular force decrease) Inotropy and lusitropy Dl 11 I LI ICT CI IUDVDLUUL. I V t~UI VC U\J 1s lusitropy („ability to relax") of the heart - shifts the enddiastolic P-V curve down • In principle, the relaxation process is ATP-dependent as well - as it is enabled by pumping out the cytosolic Ca2+ -which is, however, stable and independent on cycle phase • \|/ inotropy or lusitropy decrease an area of P-V diagram, i.e. the cardiac work decreases - compensation by RAAS and SNS increasing preload and afterload follows (similarly to the loss of peripheral resistence or circulating volume) • Those compensatory processes contribute to heart failure development in the long term. Passive contraction by elastic fibres (relaxation ability decreases) „Interests" of the heart and perfused tissues ncreaslng of cardiac work means higher energy needs for the myocardium, however the increase of circulating volume/venous return an peripheral resistance is necessary to ensure the perfusion of key organs (heart, lungs, liver, kidneys...) On contrary, systemic hypotension is often associated with lower preload (e.g. severe hemorrhage, severe diarrhea) and/or afterload (e.g. anaphylaxis, sepsis) From the heart's viewpoint, 4/ preload and 4/ afterload are advantageous, regarding the blood supply to key organs they may be linked to circulatory failure caused by circulatory system inability to keep sufficient perfusion pressure (esp. in brain circulation - shock states) • But: heart must ensure its own perfusion Regulation of circulating volume (preload) • 1^ preload in ^ systolic volume • Most substances shifting the renal - renal function curve shift function curve to the right have also vasoconstriction effects, those promoting the shift to the left are often vasodilators Regulation of systemic peripheral resistance (afterload) Vasodilatation • NO - produced in the endothelium by constitutive (eNOS) and inducible (iNOS) synthase prostacyclins histamine bradykinin p02, pC02,pH adenosine catecholamines cGMP, cAMP Vasoconstriction • endothelin • ATM • ADH • catecholamines • thromboxane A2 • Ca2+ afterload inT* peipheral resistence-systemic vasodilation of resistence arterioles Dilatation in acute cardiac insufficiency • acute reaction of the heart • a consequence of increased enddiastolic volume • enables the use of Frank-Starling mechanism in the acute cardiac insufficiency, but at the expense of higher metabolic requirement • typically as a reaction to | preload, heart failure decompensation • renal compensation of hypotension increases preload! • failing heart produces natriuretic peptides to increase diuresis Decreed compensation ^Decreased! lusitropy Cardiac output (l/min) 10- Cardiac output (l/min) 1 Glume -2 0 2 4 6 8 10 -2 0 2 4 6 8 10 Central venous pressure (mm Hg) Central venous pressure (mm Hg) www.lecturio.com/concepts/venous-function/ Dilation without hypertrophy (300 g) Concentric hypertrophy (550 g) Hypertrophic cardiomyopathy Eccentric hypertrophy (650 g) Cardiac remodelation (cellular level) • Triggered by overload • Proliferation factors reach the overloaded cardiomyocytes (catecholamines, angiotesin II, aldosterone, ADH, endotnelin-1...) • Expression of fetal genes (protooncogenes) —> fetal phenotype • shorter action potentials • contraction depends on extracellular Ca2+ (slow removal —> calcium overload) • Cardiomyocyte hypertrophy • Hypoxia in relative blood supply insufficiency (decrease of coronary blood reserve) • f 02 consumptions • microvascular compression • hypoxia changes the shape of some cells' action potentials —>• arrhythmia risk • apoptosis —>• myocardium replacement by fibrous tissue —>• impaired inotropy and lusitropy (vicious circle - see later) • autophagy - "rescue program" in hypoxic conditions (decrease of energetic needs by limiting metabolic conversion and contractile function)) • Smooth muscle cells hypertrophy —> 1s resistance (including coronary arteries) Cardiac remodelation in chronically f preload and 'f afterload • Volume overload - eccentric hypertrophy (e.g. valvular regurgitation, left-to-right shunt) • wall tension is high (law of Laplace), but lusitropy increases • Pressure overload - concentric hyperthrophy (e.g. valvular stenosis, hypertension) • all tension decreases - 4. 02 consumption, low lusitropy • Physiological h/r ratio is 0,3 - 0,4, increases during physical effort • Above 1,5 or below 0,2 decrease of CO • concentric: hypertrophic cardiomyopathy • mixed: IHD, reactive hypertrophy following myocardial infarction (eccentric in the ischemic area, concentric in unaffected part of the heart - i.e. combined systolic and diastolic dysfunction) • Athletes: eccentric in endurance disciplines, concentric in strenght disciplines (CAVE anabolics) - usually reversible • high coronary reserve phy Weeks et al., Physiology, 2011 Why (concentric) hypertrophy does not finally decrease myocardial 02 consumption a = x / 2h When wall stress (i.e. neccessity to generate higher pressure during overload) increases (together with MV02), hypertrophy initially compensates wall stress and decreases MV02 But as the myocardial mass increases, MV02 increases as well - pathological hypertrophy is not followed by adequate "densing" of coronary vessels |Fiii|ijii|iiii|iiii|Mii|iiii|iiii;iiii|nii|iMi|iiii|iiii|iiii|ii!i|iiii|iiii|tti Q 1 2 3 £ 5 6 7 & Biochemie changes in heart failure Tissue hypoxia Impaired energetic metabolism (4/ATP and creatine phosphate) Decreased utilization of fatty acids, followed by glucose tROS l^cytosolic Ca2+ • Increases the energy consumption - vicious circle Systolic and diastolic heart failure Systolic (with reduced ejection fraction) • Impaired i not ropy i i-i- j- j EDV -ESV . • 4/EF diagnosed as-, most a EDV commonly using USG • More common in men, younger patients, DCM • More often leads into the terminal heart failure Diastolic (with preseved ejection fraction -cave valvular disease) • Impaired lusitropy • Diagnosed using Doppler USG: 1^E/e' (flow through mitral valve/ mitral anulus movement at the beginning of the diastole) - blood is "pressed" rather than "sucked" into the ventricles • More common in women, older patients, hypertension, HCM, RCM, tachycardia • Prevalence of systolic and diastolic heart failure is approx. 60:40, mixed pattern is common - especially IHD Heart failure - systemic effects Left-sided failure • backward • ^hydrostatic pressure in pulmonary capillaries -> pulmonary oedema • respiratoryfailure, pleural effusion (transudate) • pulmonary hypertension -> secondary right-sided failure • forward • systemic hypotensions shock • organ failure (liver, kidneys, GIT, brain) • muscular weakness, fatigue, cachexia Right-sided failure • backward • ^hydrostatic pressure at the venous end of systemic • oedemas and effusions in systemic circulation (incl. pleural effusion) • anasarca (systemic oedema) • hepatomegaly, ascites • forward • isolated is a rarity • leads into 4/left ventricle preload -> left-sided forward failure ■ Heart failure and renal function • Low perfusion pressure in kidneys leads into lower diuresis and hypervolemia • That softens the forward effects of heart failure, but worsens the backward effects • This is more pronounced in preexisting renal failure and hypervolemia Starling forces and edema Actually pressures, or pressure gradients F = A . K . [(Pv - Pt) - o(nv - nt)], where: • F...filtration • A...filtration area • K...membrane permeability coefficient (for water) • o...membrane reflection coefficient (for proteins) The pressure gradient is directed outside at the arterial end and inside at the venous end of a capillary Exception: glomerular capillaries (high hydrostatic pressure - cave shock) Pulmonary capillaries - filtration slightly prevails all along the capillary (low both hydrostatic and oncotic pressure gradient, low reflection coefficient) But the excessive water is either drained by lymphatic vessels or breathed out, the lungs stay „dry" Capillary smaller larger I w wmot|c hydrostatic pressure = Z5mm net How out or capillary Into Ussu« = 10mm smaller hydrostatic pressure a =15rnm A r> pressure net flow into capillary = IDitwi The flow from the capillary little exceeds the reabsorption - lymphatic drainage Pulmonary edema and pleural effusion Pulmonary oedema: fluid accumulation in the lung tissue („swamp") • interstitial • alveolar • both fluid filtration and resorption from/to pulmonary circulation • treatment: medication Pleural effusion: fluid between the parietal and visceral pleura („lake") • fluid is filtrated mainly from the systemic circulation and reabsorbed mainly into the pulmonary circulation • treatment: medication or surgery • In transudates, pulmonary oedema may be combined with pleural effusion Heart failure according to rapidity of development 'A cute • De novo origin or through decompensation of chronic heart failure • Classification Killip I - IV Chronic Slow development Classification NYHA l-IV Heart failure treatment Acute • Treatment of initiating cause • Rest in bed, hospitalization • o2 • Diuretics • Vasodilators (if not severe hypotension - i.e. „warm and wet" failure) • Vasopressors (in cardiogenic shock - „cold and wet") • Inotropics (e.g. catecholamines) • Opioids in dyspnea • Mechanical circulatory support Chronic • Treatment of initiating cause • Mild physical load • Conditioning training 3-5 times per a week 20-30 min • Diuretics • Heart rate reduction (6-blockers, digoxin, ivabradine) • RAAS inhibition (prevents remodelling) • Implantation of ICD, BiV PM (arrhythmia) • Heart transplantation