Ischemic Heart Disease

M Adhitya Nagara
Universitas Sriwijaya
Clinical definition
Condition in which imbalance between myocardial oxygen supply and demand
results in myocardial hypoxia and accumulation of waste metabolites, most often
caused by atherosclerotic disease of the coronary arteries.
Determinants of myocardial supply and
demand
Myocardial oxygen supply
Oxygen content – determined by the
hemoglobin concentration and the degree
of systemic oxygenation.
Myocardial oxygen supply
 
Coronary blood flow is much more
dynamic, and regulation of the flow is
responsible for matching the oxygen
supply with metabolic requirements.
Myocardial oxygen supply
Perfusion pressure can be approximated
by aortic diastolic pressure.
Can be decreased by hypotension and
aortic valve regurgitation.
Myocardial oxygen supply
Coronary vascular resistance is modu-
lated by external compression and fac-
tors that alter intrinsic coronary tone.
External compression
Exerted on the coronary vessels during the cardiac cycle by the contraction of
surrounding myocardium.
Directly related to intramyocardial pressure, therefore greatest during systole.
Subendocardium is subjected to a greater force, thus it is most vulnerable to ischemic
damage.
Intrinsic control of arterial tone
Additional oxygen requirement must be met by an increase in blood flow.
Autoregulation of coronary vascular resistance is the most important mediator in this
process.
Factors that contribute: accumulation of local metabolites, endothelium-derived
substances, and neural innervation.
Metabolic factors – during hypoxemia, the generation of high-energy phosphates,
including ATP, is impaired. Consequently, ADP and AMP accumulate and are
subsequently degraded into adenosine. Other metabolites includes lactate, acetate,
hydrogen ions, and carbon dioxide.
Intrinsic control of arterial tone (cont’d)
Endothelial factors – endothelial cells of
the arterial wall produce vasoactive
substances: nitric oxide, prostacyclin, and
endothelium-derived hyperpolarizing
factor (EDHF).
Intrinsic control of arterial tone (cont’d)
Neural factors – under normal circumstances, sympathetic receptors play an
important role. Coronary vessels contain α-adrenergic (vasoconstriction) and β2-
adrenergic (vasodilatation).
Myocardial oxygen demand
 
Wall stress – the force acting on the
myocardial fibers, tending to pull them
apart.
Myocardial oxygen demand
Heart rate – when increased, the number
of contractions and the amount of ATP
consumed per minute increases.
Contractility – a measure of the force of
contraction.
Pathophysiology of ischemia
Research has demonstrated that the reduction of blood flow results from the
combination of fixed vessel narrowing and abnormal vascular tone, contributed to by
atherosclerosis endothelial cell dysfunction.
Pathophysiology of ischemia
Fixed cell narrowing
The hemodynamic significance of fixed atherosclerotic coronary artery stenosis
relates to both the fluid mechanics and the anatomy of the vascular supply.
Pathophysiology of ischemia
Fixed cell narrowing
 • Fluid mechanics Thus, vascular resistance is
governed, in part, by the
geometric component of L/r4.
, Hemodynamic significance of a
stenotic lesion depends on its
length and the degree of vessel
• Vascular resistance narrowing.
Pathophysiology of ischemia
Fixed cell narrowing
Anatomy – the coronary artery consists of large proximal epicardial segments and
smaller, distal resistance vessels (arterioles).
Proximal vessels are subject to overt atherosclerosis, while distal vessels can adjust
their vasomotor tone.
These resistance vessels serve as a reserve, increasing their diameter with exertion to
meet increasing oxygen demand and dilating, even at rest, if a proximal stenosis is
severe.
Pathophysiology of ischemia
Fixed cell narrowing
The hemodynamic significance of a coronary
artery narrowing depends on both the degree of
stenosis of the epicardial portion of the vessel
and the amount of compensatory vasodilatation
the distal resisance vessels are able to achieve.
Pathophysiology of ischemia
Endothelial cell dysfunction
Contributes to the pathophysiology of ischemia in two ways: (1) by inappropriate
vasoconstriction of coronary arteries and (2) through loss of normal antithrombotic
properties.
In patients with dysfunctional endothelium, the release of endothelial vasodilators is
impaired.
Factors released from endothelial cells (including NO and prostacyclin) exert
antithrombotic properties.
Pathophysiology of ischemia
Other causes
Decreased perfusion pressure due to hypotension (e.g., in a patient with
hypovolemia or septic shock).
Severely decreased oxygen content (anemia, impaired oxygenation of the blood by
the lungs).
Consequences of ischemia
It reflects the inadequate oxygenation and local accumulation of metabolic waste
products.
During ischemia, myocites convert to anaerobic metabolic pathways which results in
transient reduction of both ventricular systolic contraction and diastolic relaxation.
The consequent elevation of LV diastolic pressure to the pulmonary capillaries can
precipitate pulmonary congestion.
Metabolic products (lactate, serotonin, and adenosine) accumulation is suspected to
activate peripheral pain receptors and arrhythmias.
Consequences of ischemia
The fate of myocardium depends on the severity and duration of imbalance between
oxygen supply and demand.
Ischemic cardiac injury results in either irreversible myocardial necrosis or rapid and
full recovery of myocite function.
It is also now known that sometimes it can result in a period of prolonged contractile
dysfunction without myocite necrosis – such as stunned myocardium and
hibernating myocardium.
Consequences of ischemia
Ischemic syndromes
Consequences of ischemia
Ischemic syndromes

A pattern of predictable, transient chest discomfort during exertion or emotional

stress generally caused by obstructive atheromatous plaque in one or more
coronary arteries.
During the period that oxygen demand exceeds supply, ischemia results, often
accompanied by chest discomfort of angina pectoris.
Consequences of ischemia
Ischemic syndromes

A patient with chronic stable angina may experience a sudden increase in the tempo
and duration of ischemic episodes.
Occuring with lesser degrees of exertion and even at rest.
Consequences of ischemia
Ischemic syndromes

Local coronary artery spasm in the absence of atherosclerotic lesions known as

prinzmetal angina.
The mechanism is not completely understood but may involve increased
sympathetic activity in combination of endothelial dysfunction.
Clinical features of chronic stable
angina
The most important clinical evaluation of ischemic heart disease is the history
described by patient: quality, location, accompanying symptoms, precipitants,
frequency, risk factors.
Quality – angina is most often described as a pressure, discomfort, tightness, burning,
or heaviness. The patient may place a clenched fist over the sternum referred to as
Levine sign.
Location – is usually diffuse rather than localized to a single point.
Accompanying symptoms – tachycardia, diaphoresis, nausea, dyspnea, transient
fatigue and weakness.
Clinical features of chronic stable
angina
Precipitants – angina is precipitated by conditions that increase myocardial oxygen
demand. These include physical exertion, anger, and other emotional excitement.
Frequency – varies considerably because patients quickly learn which activities cause
their discomfort and avoid them.
Risk factors – a careful history should uncover risk factors to atherosclerosis and
CAD, including cigarette smoking, dyslipidemia, hypertension, diabetes, and family
history of premature coronary disease.
Clinical features of chronic stable
angina
Differential Diagnosis
 Cardiac
o Myocardial ischemia
o Pericarditis
 Gastrointestinal
o Gastroesophageal reflux
o Peptic ulcer disease
o Esophageal spasm
o Biliary colic
 Musculoskeletal
o Costochondral syndrome
o Cervical radiculitis
Clinical features of chronic stable
angina Increased heart rate and blood pressure
due to augmented sympathetic response.
Myocardial ischemia may lead to
papillary muscle dysfunction and
therefore mitral regurgitation.
Decreased ventricular compliance
produces stiffened ventricle, therefore an
S4 gallop during atrial contraction.
Diagnostic studies
Electrocardiogram
Diagnostic studies
Stress testing – to rule out underlying ischemic heart disease, provocative exercise
or pharmacologic stress tests are valuable diagnostic and prognostic aids.
Standard exercise testing – the patient exercises to progressively higher workloads
and is observed for chest discomfort or excessive dyspnea.
Pharmacologic stress tests – for patients unable to exercise, through the use of
vasodilators or inotropes.
Diagnostic studies
Coronary angiography

• Injection of the right coronary artery

demonstrates stenosis of the
midportion of the vessel.
Diagnostic studies
Noninvasive imaging of coronary arteries – coronary CT angiography (CCTA)
performed with administration of intravenous contrast can visualize stenosis of
greater than 50%.
Approximate sensitivity is 90% while specificity is 65% - 90%.
CCTA without contrast can be used as a screening test to detect artery calcification,
which correlates with the extent of atherosclerosis and thus estimates plaque burden.
Natural history
The patient with chronic angina may show no change in a stable pattern. However,
the course maybe punctuated by the occurrence of unstable angina, MI, or sudden
cardiac death. This is often related to vulnerability of the plaque to rupture.
Mortality has significantly declined in recent decades. This is likely related to
improved lifestyle changes, improved therapeutic strategies and longevity following
ACS, and advances in pharmacologic and mechanical therapies for chronic CAD.
Treatment
The goals of therapy are to decrease the frequency of anginal attacks, prevent
acute coronary syndromes, and prolong survival.
This is done by addressing the risk factors that led to the development of
atherosclerotic heart disease: smoking cessation, cholesterol improvement, and BP
control.
Treatment
Drug class Mechanism of action Adverse effects
Organic nitrates ↓ myocardial oxygen demand Headche
↓ preload Hypotension
↑ O2 supply Reflex tachycardia
↑ coronary perfusion
↑ coronary vasospasm
β-blockers ↓ myocardial oxygen demand Excessive bradycardia
↓ contractility ↓ LV contractile dysfunction
↓ heart rate Bronchoconstriction
May mask hypoglycemic symptoms
Fatigue
Treatment
Drug class Mechanism of action Adverse effects
Calcium channel blockers ↓ myocardial oxygen demand Headache, flushing
↓ preload (venodilatation) ↓ LV contractility (V, D)
↓ wall stress (↓ BP) Marked bradycardia (V, D)
↓ contractility (V, D) Edema (especially N, D)
↓ heart rate (V, D) Constipation (esp. V)
↑ O2 supply
↑ coronary perfusion
↑ coronary vasospasm
Ranolazine ↓ late phase inward sodium current Dizziness, headache
Constipation, nausea
Treatment
Medical treatment to prevent acute cardiac events
Antiplatelet therapy (e.g., aspirin) has antithrombotic actions though the
inhibition of synthesis of thromboxane A2, as well as anti-inflammatory properties.
Platelet P2Y12 ADP receptor antagonists, such as clopidogrel, also prevent
platelet activation and aggregation.
Lipid regulation therapy, in particular, HMG-CoA reductase inhibitors (statins)
lower MI and death rates in patients with established coronary disease. An LDL
less than 70 mg/dL is a common goal for patients with CAD.
ACE-inhibitors are beneficial in the treatment of hypertension, heart failure, and
following MI.
Treatment
Revascularization – is pursued if (1) the patient symptoms of angina do not respond
adequately to drug therapy, (2) unacceptable side effects of medications occur, (3) the
patient is found to have a high risk coronary disease.
The two techniques to accomplish mechanical revascularization are percutaneous
coronary intervention (PCI) and coronary artery bypass graft (CABG).
Treatment
PCI includes percutaneous transluminal
coronary angioplasty (PTCA), a
procedure performed under fluoroscopy in
which a balloon-tipped catheter is inserted
through peripheral artery.
Coronary stents developed for
implantation at the time of PCI have been
shown to significantly reduce the rate of
restenosis.
Treatment
CABG surgery entails grafting portions of a
patient’s native blood vessels to bypass
obstructed coronary arteries.
Two types of surgical grafts are used; the first
employs native veins, typically a section of
saphenous vein (superfluous vessel from the
leg); the second uses arterial grafts—most
commonly, an internal mammary artery.
thank you