METABOLISM OF MYOCARDIUM
ISCHEMIC HEART DISEASE
MYOCARDIAL INFARCTION
VLA October 10, 2017
METABOLISM OF THE HEART
 The heart is an omnivore organ, which utilizes a
diverse set of fuel substrates, including lactate,
glucose, amino acids, ketones, and particularly
free fatty acids.
 Newborns –preferentially-glucose (FAs with a
long chains are needed for myelinisation)
 Healthy adults - lipids
 Ischemic adults - anaerobic glycolysis only
(ATP)
 Diabetic adults – also ketones
 Patients with heart failure - toxic effects of both
glucose and lipid metabolism
EPICARDIAL ADIPOSE TISSUE
Epicardial portion – between inner surface of
visceral layer of pericardium and myocardium
(without fascia- common microcirculation)origin-splanchnopleuric
mesoderm- supplied by
aa. coronarie.
Similar to brown tissue (high expression UCP-1,
modulation of the heat production for heart
during changes of thermoregulation, protection
against effects of ischemia/ hypoxia with great
hemodynamical effects, maybe characteristics
of beige fat)
EPICARDIAL ADIPOSE TISSUE
 Pericardial (paracardial) portion- betwen
external surface of external pericardial
layer and thoracic wall – primitive
thoracic mesenchym –supplied by a.
mammaria int.
EAT AND CORONARY MICROCIRCULATION
 EAT is an ectopic visceral adipose tissue that directly contacts the
myocardium and coronary arteries. EAT accumulation is reported
to be associated with coronary atherosclerosis and unfavorable
cardiovascular outcomes independent of traditional CAD risk
factors.
 Pericoronary fat volume was positively associated with the
presence of plaque independent of total EAT volume .
 CFR (coronary flow reserve) is dependent on the combined
effects of epicardial coronary stenosis and microvascular
dysfunction. There is the possibility of a paracrine role of
periventricular EAT on the coronary microcirculation.
PERIVENTRICULAR EAT AND DIASTOLIC
FUNCTION
 Obesity is an important risk factor for LV diastolic dysfunction,
which has been shown to be a predictor of heart failure
development. However, the underlying mechanism linking obesity
to LV diastolic dysfunction has not been fully elucidated.
 Increased periventricular EAT volume seems to be 1 of the
important causes of diastolic dysfunction and impaired CFR may
be involved in the association between periventricular EAT and
diastolic dysfunction.
 Periventricular EAT may affect LV relaxation but not LV
compliance. Periventricular EAT may serve as a potential
therapeutic target for diastolic dysfunction.
ATHEROSCLEROSIS DEVELOPMENT
 Initiation
 Inflammation
 Fibrous cap formation
 Plaque rupture
 Thrombosis
FUNCTIONAL ENDOTHELIUM
 Constant vasodilation
 Antiadhesive state (NO, PGI2)
 Constant local anticoagulation and
fibrinolytic state (increase of AT III,
protein C, protein S, tPA, PAI-1)
ENDOTHELIAL DYSFUNCTION- CAUSES
 LDL modification (oxidation, glycation,
immune complex formation).
 Expression of adhesive molecules
 Cytokines release (attraction and migration
of proinflammatory cells to subendothelial
space).
 Prothrombotic phenotype of dysfunctional
endothelium
Crossection of normal vessel
Stable angina pectoris
Unstable angina pectoris
Myocardial infarction
Decreasedbloodflow
„RESPONSE-TO-RETENTION“ MODEL OF ATHEROGENESIS
 Atherogenesis is initiated by focal retention of ApoB on molecules of
subendothelial matrix, especially on proteoglycans.
 Adherent lipoproteins are modified (by aggregation and/ or oxidation),
which lead to maladaptive inflammatory response. Monocytes enter
subendothelial space, differentiate to macrophages and that
phagocyte adherent and modified lipoproteins. They become
gradually foam cells. Another cells as T-lymphocytes, mast cells and
other ones enter the developing lesion and take part in maladaptive
inflammatory response. The process is accelerating by increased
retention of lipoproteins in atherosclerotic plaques.
 Smooth muscle cells (SMCs) migrate to intima and support production of
collagen fibrous cap which seems to be remodelling response of
vascular wall (similar to scar) to damage.
 During atherosclerotic lesion progression focal necrotic lesions with
death macrophages are formed. In these lesions accumulation of
extracellular debris, cholesterol crystals, proteases and procoagulation/
trombogenic material can be observed. This leads to attenuation of
fibrous cap, erosion and/ or rupture of the plaque and development of
acute thrombotic vascular event (MI, cerebral stroke).
„RESPONSE-TO-RETENTION“ MODEL OF ATHEROGENESIS
 Cytokine release (platelet-derived growth factor a transforming
growth factor-β (TGF-β) from monocytes, macrophages and/ or
damaged endothelial cells support further accumulation of
macrophages and migration and proliferation of smooth muscle
cells
Plaque rupture and plaque erosion in ACS. (Modified from: Crea
F, Liuzzo G: J Am Coll Cardiol. 2013;61(1):1-11)
Current Cardiology Reports
September 2017, 19:84
INFLAMMATION AND PLAQUES
Inflammation contributes to many of the characteristics of plaques
implicated in the pathogenesis of acute coronary syndromes (ACS).
Two major mechanisms precipitate most ACS:
 a rupture of the plaque fibrous cap, which causes most fatal acute
myocardial infarctions (higher degree of inflammation), and
 a superficial erosion of the intima (lower degree of inflammation)
Thin fibrous caps, measured in many studies at ≈ 60 to 70 μm, are one of the
most studied characteristics of plaques that cause ACS. Inflammatory
signals, such as the T helper 1 (TH1) cytokine γ-interferon, impair the ability of
the smooth muscle cell (SMC), to synthesize new collagen required to repair
and maintain the extracellular matrix of the fibrous cap. On the other hand,
matrix-degrading proteinases, tightly regulated by inflammatory mediators,
strongly contribute to the dissolution of interstitial collagen that weakens the
fibrous cap and hence renders a plaque susceptible to rupture.
Current Cardiology Reports
September 2017, 19:84
INFLAMMATION AND PLAQUES
 A dysregulation of adaptive immunity is a major feature of ACS.
The abnormalities of CD4+helper T-cell subpopulations are also
associated with worse outcomes, especially in patients with
diabetes mellitus. Such alterations characterize about half of ACS
patients, and may concern the number or the function of T-cells
with a differentiation oriented toward aggressive effector
phenotypes and/or defective regulatory T-cells that are involved
in the suppression of an excessive immune response. This
imbalance might contribute to plaque destabilization through
multiple pathways, among which the alteration of the normal
biological outcome of immune responses seems to be the most
relevant.
Current Cardiology Reports
September 2017, 19:84
INFLAMMATION AND PLAQUES
 A marked increase in Th1 frequency and increased expression of
Th1-related cytokines such as IFN-γ were reported. By releasing
their signatory cytokine IFN-γ, Th1 cells contribute to increase the
fragility of the fibrous cap, as well as the thrombogenic potential
of the plaque. Indeed, IFN-γ is involved in the recruitment and
activation of macrophages, in the reduction of collagen synthesis,
and in the increase of extracellular matrix-degrading proteins.
Among helper T-cells, CD4+CD28null T-cells might be considered a
different lymphocyte subset for several aspects. This
subpopulation of T-cells, with increased resistance to apoptosis
and a wide range of pro-inflammatory properties (above all
increased production of IFN-γ and TNF-α), is strongly associated
with ACS; since CD4+CD28null T-cells are present preferentially in
unstable ruptured atherosclerotic plaques and their frequency
shows a direct relation with the risk of ACS.
Current Cardiology Reports
September 2017, 19:84
INFLAMMATION AND PLAQUES
 Recently, the introduction of a T-cell subset, Th17,
characterized by the expression of a different
transcription factor (retinoid-related orphan receptor,
ROR-γt), and by the production of IL-17, was reported.
 IL-17 seems to be predominantly pro-atherogenic.
Increased levels of Th17 and Th17 associated cytokines,
such as IL-17, IL-21 and IL-23, have been described in
atherosclerotic carotid artery plaques and found to be
associated with the progression of atherosclerotic
disease and with plaque vulnerability.
Current Cardiology Reports
September 2017, 19:84
INFLAMMATION AND PLAQUES
 Indeed, Th17 cells with features overlapping both inducible Tregs
(IL-17/IL-10 dual producing T cells) and Th1 (IL-17/IFNγ dual
producing T cells) have been described. On the other hand, the
role of Treg in the atherosclerotic disease is well known. This T-cell
subpopulation inhibits atherosclerosis development and
progression by suppressing effector T-cell responses.
 ACS patients show low levels of circulating Treg, a reduced
suppressive efficiency of Treg and an increased Treg susceptibility
to apoptosis. ACS patients have a lower induction of Treg after Tcell
receptor (TCR) in vitro stimulation. Moreover, Treg from
unstable plaque shows a restricted TCR diversity, suggesting an
increased antigen-specific Treg redistribution between the
peripheral blood and local sites of inflammation.
Current Cardiology Reports
September 2017, 19:84
Role of inflammation in heart failure
development and plaque instability.
(Modified from: Crea F, Liuzzo G: J Am Coll
Cardiol. 2013;61(1):1-11)
Current Cardiology Reports
September 2017, 19:84
INFLAMMATION AND HEART FAILURE
 One of the first steps of the relationship between
inflammation and heart failure is the dysregulation of
autophagy and subsequent accumulation of reactive
oxygen species (ROS), leading to activation of Toll-like
receptors (TLR-s) signaling pathways. In particular,
there is evidence that the impairment of dysfunctional
mitochondrial autophagy (called mitophagy) can
lead to low-grade release of DAMPs, important triggers
of pathological inflammation.
Current Cardiology Reports
September 2017, 19:84
INFLAMMATION AND HEART FAILURE
 Mitochondrial DNA (mtDNA) can be released into the
circulation by injured cells (secondary to impairment in
mitophagy) and then recognized by TLR9 of
polymorphonuclear neutrophils (PMNs), with
subsequent proinflammatory cytokines production
(TNF-α, IL-1β, and IL-6).
 Direct activation of NLRP3 inflammasome by oxidized
mitochondrial DNA, a key element of inflammatory
response in acute coronary syndrome and heart failure
was shown.
Current Cardiology Reports
September 2017, 19:84
DAMPS, PAMPS, AND TLR-4 SIGNALING
ACTIVATION
 It is known that Toll-like receptor 4 (TLR4) plays a pivotal role in
atherosclerosis development through activation of interleukin-1
receptor associated kinases (1, 2, and 4) and the transcription
factor nuclear factor-κB (NF-κB), leading to the expression of a
wide range of inflammatory genes. Moreover, TLR-4 signaling
involves downregulation of the sterol transporters ABCA1 and
ABCG1 in macrophages and upregulation of very low density
lipoprotein receptor, and adiponectin receptor 2, thus increasing
foam cells formation, and mediates activation of
metalloproteinases with plaque destabilization.
 A similar role for TLR-4 inflammatory pathway involved in the
establishment and progression of chronic HF was shown.
Current Cardiology Reports
September 2017, 19:84
DAMPS, PAMPS, AND TLR-4 SIGNALING
ACTIVATION
 TLRs recognize specific ligands, termed damage-associated
molecular patterns (DAMPs) and pathogen-associated molecular
patterns (PAMPs), from damaged host cells and pathogens,
respectively. During cardiac stress, above all ischemic injury or
hypertension and metabolic syndrome, a conspicuous release of
DAMPs by cardiomyocytes has been described, such as highmobility
group box 1 (HMGB1)and heat shock protein 60 (HSP 60).
 As for DAMPs, pathogen-associated molecular patterns (PAMPs)
can also promote activation of TLRs signaling, determining
transition from viral myocarditis to heart failure.
 High doses of LPS induce production of several proinflammatory
cytokines in macrophages through marked activation of TLR-4,
nuclear factor κB, and the NOD-like receptor family pyrin domain–
containing protein 3 (NLRP3) inflammasome, leading to ongoing
inflammatory signaling and eventually to LV dysfunction.
Current Cardiology Reports
September 2017, 19:84
DIFFERENT MACROPHAGES LINEAGE AS PROTAGONISTS OF
ONGOING INFLAMMATION IN HEART FAILURE AND THE CONTRIBUTION
OF NLRP-3 INFLAMMASOME
 Recently, distinct cardiac macrophage subsets were identified, which have their
own separate origins and function.
 Total cardiac macrophage numbers expanded through two different pathways:
C-C motif chemokine receptor 2 (CCR2)-mediated monocyte recruitment and
local proliferation of resident macrophages. These two macrophage lineages are
characterized by different properties and may exert different roles in the complex
interplay of pathological and physiological inflammation at the base of heart
failure development. Resident macrophages are enriched in reparative genes
expressions, while recruited CCR2+ macrophages are enriched in inflammatory
genes, in particular the NOD-like receptor family pyrin domain–containing protein
3 (NLRP3) inflammasome pathway. The activated inflammasome is a powerful
mediator of the immune response via caspase-1 activation of IL-1β and IL-18.
Moreover, the NLRP3 inflammasome can also induce pyroptosis in a caspase-1dependent
manner, leading to loss of cardiomyocytes and subsequent reduction
of contractile reserve leading to HF progression. Usually, pyroptosis is a highly
inflammatory form of programmed cell death that occurs upon infection with
intracellular pathogens and is likely to form part of the antimicrobial response .
Current Cardiology Reports
September 2017, 19:84
DIFFERENT MACROPHAGES LINEAGE AS PROTAGONISTS OF
ONGOING INFLAMMATION IN HEART FAILURE AND THE CONTRIBUTION
OF NLRP-3 INFLAMMASOME
 In this context, the initiation of pyroptosis in macrophages may be caused by the
recognition of pathogen-associated molecular patterns (PAMPs) by NOD-like
receptors (NLRs) secondary to various microbial triggers, such as viral myocarditis
or LPS released by gut microbiota in metabolic syndrome, associated with heart
failure development.
 Furthermore, in the setting of diabetic cardiomyopathy inflammasome activation
dependent on the combination of oxidative stress and reactive oxygen species
production, because of mitochondrial dysfunction was shown, leading to
increased susceptibility to atherosclerosis, dyslipidemia, hypertension, and the
prothrombotic state, which ultimately can lead to heart failure development.
 Finally, another contribution to the establishment of heart failure comes from the
profibrotic pathways elicited by recruited cardiac macrophages, which play a
pivotal role in the transdifferentiation of fibroblasts to myofibroblasts through
expression of transforming growth factor (TGF)-β. Also in this setting, NLRP3 was
found to represent a key element through regulation of mitochondrial ROS (mROS)
production and Smad signaling, ultimately leading to profibrotic gene expression.
Current Cardiology Reports
September 2017, 19:84
Role of PAMPs in the inflammatory atherosclerotic burden.
(Modified with permission from: La Rosa G, Biasucci LM. Cardio
Innov Appl. 2016;1(4):433-442(10);
Current Cardiology Reports
September 2017, 19:84
MYOCARDIAL ISCHEMIA
 Myocardial ischemia results in numerous deleterious
consequences at the level of the cardiac myocyte that, if
left uncorrected, culminate in necrotic cell death.
 A major consequence of myocardial ischemia is the
depletion of adenosine triphosphate (ATP) and other high
energy phosphates due to cessation of aerobic metabolism
and oxidative phosphorylation. Because the continually
contracting myocardium is highly dependent on aerobic
metabolism, ATP depletion occurs rapidly in the ischemic
heart and contractility is halted within 60 s.
 ATP depletion is leading to: decreased relaxation of
myofilaments, glycogen depletion, disruption of ionic
equilibrium and cell swelling.
MYOCARDIAL ISCHEMIA
 Nevertheless, these effects can be reversed and normal myocyte
contractile function restored if the duration of ischemia is
sufficiently brief (generally considered to be less than 20 min of
severe ischemia).
 If the ischemia is prolonged, irreversible injury will develop, which is
characterized by damage and/or disruption of the myocyte
sarcolemmal membrane.
 Plasma membrane damage leads to loss of osmotic balance and
the leakage of cellular metabolites into the extracellular space.
 Damage to the mitochondrial membranes compromises the cell's
ability to generate ATP upon reperfusion, as well as results in
release of mitochondrial proteins that can directly stimulate the
apoptotic cell death pathway (mitoptosis).
 Disruption of lysosomal membranes is especially dire, as this can
lead to the release of degradative enzymes capable of digesting
essentially all cellular constituents, invariably leading to cellular
necrosis.
ACUTE MYOCARDIAL ISCHEMIA
 Acute myocardial ischemia was find to induce early
increases (10 min) of circulating glucose, lactate,
glutamine, glycine, glycerol, phenylalanine, tyrosine,
and phosphoethanolamine; decreases in cholinecontaining
compounds and triacylglycerols; and a
change in the pattern of total, esterified, and
nonesterified fatty acids. Creatine increased 2 h
after ischemia.
 Using multivariate analyses, a biosignature was
developed that accurately detected patients with
MIS both in the setting of angioplasty-related MIS
(area under the curve 0.94) and in patients with
acute chest pain (negative predictive value 95%).
ISCHEMIA/REPERFUSION-INDUCED CELL DEATH
 In addition to necrosis, apoptosis also contributes
significantly to myocyte death during
ischemia/reperfusion-induced cell death (IR).
While apoptotic myocyte death is most
pronounced in the reperfused myocardium,
apoptosis has also been shown to contribute to
cell death in ischemic-only hearts.
 In addition, a more recently defined form of cell
death known as necroptosis or “programmed
necrosis,” a form of cell death with
characteristics of both necrosis and apoptosis,
has been suggested to contribute to myocyte
death during IR. It can improved by ghrellin.
MYOCYTE CALCIUM HOMEOSTASIS
 Loss of myocyte calcium homeostasis results in a number of
cellular changes that predispose the myocyte to irreversible injury.
 Mitochondrial calcium overload is the primary stimulus for
mitochondrial permeability transition (MPT), a stress response
mediated by the opening of a high conductance pore located
on the inner mitochondrial membrane. While enhanced
intracellular calcium concentration is capable of directly
stimulating apoptosis, elevated calcium levels can also stimulate
the activation of numerous intracellular degradative enzymes with
the potential to damage several different cellular structures and
precipitate cell death, including phospholipases, proteases and
endonucleases. Activation of phospholipases can lead to the
damage of cellular membranes which, as described above, can
lead to necrotic cell death as a consequence of disruption of
cellular osmotic balance and the release of lysosomal enzymes in
the cytoplasm. The ionic imbalances have further consequences.
Causes and consequences of
ionic imbalances during
ischemia.
Ischemia results in a cessation of aerobic
metabolism and a reliance on anaerobic
metabolism, resulting in cellular and tissue
acidosis. Accumulation of intracellular H+
stimulates NHE, resulting in accumulation of
intracellular Na+. Accumulation of
intracellular Na+, in turn, stimulates reverse
activity of the NCX, resulting in intracellular
Ca2+ accumulation. If ischemia is sustained,
cellular Ca2+ overload may develop, resulting
in activation of degradative enzymes (e.g.,
proteases, phosphatases and
endonucleases), and stimulation of MPT,
culminating in myocyte death. NHE, Na+/H+
exchanger; NCX, Na+/Ca2+ exchanger; MPT,
mitochondrial permeability transition.
Adam J. Perricone , Richard S. Vander Heide
Novel therapeutic strategies for ischemic heart disease
Pharmacological Research, Volume 89, 2014, 36 - 45
http://dx.doi.org/10.1016/j.phrs.2014.08.004
METABOLISM OF THE HEART IN ISCHEMIC CONDITIONS
 Dramatic and immediate changes take
place in cardiac and global metabolism
as a consequence of insufficient blood
flow to meet the myocardium energy
needs and secondary to the subsequent
stress response.
 These mechanisms include a decrease of
β-oxidation and an increase of glycolysis
and lactate release among others.
CORONARY ARTERY DISEASE (CAD)
 Multifactorial etiology, frequent risk factors
 Uninfluenced: genetics, age, sex, rase, family
history, low socioeconomic state (?)
 Influenced: total cholesterol, smoking, diabetes
mellitus, hypertension, life style,
 We can observe patients with CAD without these
risk factors.
ACUTE AND CHRONIC ISCHEMIC HEART DISEASES
 Acute coronary syndrom – generally
related to unstable angina pectorismyocardial
infarction
 Stable angina pectoris – chest pain
during exercise
 Unstable angina pectoris – chest pain in
rest conditions
 Prinzmetal´s angina pectoris – due to
spasms
Relations among coronary arteries state and clinical
syndrome.
MYOCARDIAL INFARCTION
 Clinical signs:
 Pain, angina-like after exercise. Brief onset,
during rest, several hours. Pain intensity
oscillating, in 20% patients without pain feeling.
S.c. ‚silent' MI usually in diabetic patients and
older individuals.
 Vegetative nerve system activation: sweat,
nausea, vomiting, fatique, unrest,
 Patents pale, grey, sweaty
 Sinus tachykardia (sympathetic nerve systém
activation)
 Slight fever (to 38°C) during 5 first days
DIAGNOSIS OF MI
At least two signs:
Chest pain
Corresponding changes on ECG
Increase of cardiac biomarkers
MI Signs on ECG
Q wave, ST elevation, T wave inversion
MI on ECG
HEART BIOMARKERS
Another markers of acute coronary syndrome
SIGNS AND SYMPTOMS
Acute MI can have unique manifestations in individual patients. The degree
of symptoms ranges from none at all to sudden cardiac death. An
asymptomatic MI is not necessarily less severe than a symptomatic event,
but patients who experience asymptomatic MIs are more likely to be
diabetic. Despite the diversity of manifesting symptoms of MI, there are some
characteristic symptoms.
 Chest pain described as a pressure sensation, fullness, or squeezing in the
midportion of the thorax
 Radiation of chest pain into the jaw or teeth, shoulder, arm, and/or back
 Associated dyspnea or shortness of breath
 Associated epigastric discomfort with or without nausea and vomiting
 Associated diaphoresis or sweating
 Syncope or near syncope without other cause
 Impairment of cognitive function without other cause
An MI can occur at any time of the day, but most appear to be clustered
around the early hours of the morning or are associated with demanding
physical activity, or both. Approximately 50% of patients have some warning
symptoms (angina pectoris or an anginal equivalent) before the infarct.
PATHOPHYSIOLOGY SUM OF MI
 Most myocardial infarctions are caused
by a disruption in the vascular
endothelium associated with an unstable
atherosclerotic plaque that stimulates
the formation of an intracoronary
thrombus, which results in coronary artery
blood flow occlusion. If such an
occlusion persists for more than 20
minutes, irreversible myocardial cell
damage and cell death will occur.
 flow, an MI can result.
PATHOPHYSIOLOGY SUM OF MI
 The development of atherosclerotic plaque occurs over a
period of years to decades.
 The two primary characteristics of the clinically symptomatic
atherosclerotic plaque are a fibromuscular cap and an
underlying lipid-rich core. Plaque erosion can occur
because of the actions of matrix metalloproteases and the
release of other collagenases and proteases in the plaque,
which result in thinning of the overlying fibromuscular cap.
The action of proteases, in addition to hemodynamic forces
applied to the arterial segment, can lead to a disruption of
the endothelium and fissuring or rupture of the fibromuscular
cap. The loss of structural stability of a plaque often occurs
at the juncture of the fibromuscular cap and the vessel wall,
a site otherwise known as the shoulder region. Disruption of
the endothelial surface can cause the formation of
thrombus via platelet-mediated activation of the
coagulation cascade. If a thrombus is large enough to
occlude coronary blood flow, an MI can result.
PATHOPHYSIOLOGY SUM OF MI
 The death of myocardial cells first occurs in the area of
myocardium most distal to the arterial blood supply: the
endocardium. As the duration of the occlusion increases,
the area of myocardial cell death enlarges, extending from
the endocardium to the myocardium and ultimately to the
epicardium. The area of myocardial cell death then
spreads laterally to areas of watershed or collateral
perfusion.
 Generally, after a 6- to 8-hour period of coronary occlusion,
most of the distal myocardium has died. The extent of
myocardial cell death defines the magnitude of the MI. If
blood flow can be restored to at-risk myocardium, more
heart muscle can be saved from irreversible damage or
death.
PATHOPHYSIOLOGY SUM OF MI
 The severity of an MI depends on three factors:
 the level of the occlusion in the coronary artery,
 the length of time of the occlusion, and
 the presence or absence of collateral circulation.
Generally, the more proximal the coronary occlusion, the more extensive the
amount of myocardium that will be at risk of necrosis. The larger the
myocardial infarction, the greater the chance of death because of a
mechanical complication or pump failure. The longer the period of vessel
occlusion, the greater the chances of irreversible myocardial damage distal
to the occlusion.
STEMI (=MI with ST elevation) is usually the result of complete coronary
occlusion after plaque rupture. This arises most often from a plaque that
previously caused less than 50% occlusion of the lumen.
NSTEMI (= MI without ST-elevation) is usually associated with greater plaque
burden without complete occlusion. This difference contributes to the
increased early mortality seen in STEMI and the eventual equalization of
mortality between STEMI and NSTEMI after 1 year.
PRECIPITATING CAUSES OF HEART FAILURE
1. ischemia
2. change in diet, drugs or both
3. increased emotional or physical stress
4. cardiac arrhythmias (eg. atrial fib)
5. infection
6. concurrent illness
7. uncontrolled hypertension
8. new high output state (anemia, thyroid)
9. pulmonary embolism
10. mechanical disruption (sudden MR…)
NYHA FUNCTIONAL CLASSIFICATION
 Class I: patients with cardiac disease but
no limitation of physical activity
 Class II: ordinary activity causes fatigue,
palpitations, dyspnea or anginal pain
 Class III: less than ordinary activity causes
fatigue, palpitations, dyspnea or
angina
 Class IV: symptoms even at rest conditions
STAGES OF HEART FAILURE
 Stage A
 High risk for development of heart failure
 Stage B
 Structural heart disease
 No symptoms of heart failure
 Stage C
 Symptomatic heart failure
 Stage D
 End-stage heart failure
DÍKY ZA POZORNOST