Symptoms in patients with stable angina pectoris typically follow the pattern of demand angina, in which the chest discomfort is exacerbated by increased myocardial oxygen demand, for example, exertion or emotional upset. Stable angina generally has a benign prognosis because the brief episodes of ischemia do not damage the heart, but instead increase the ability of the myocardium to withstand a fall in blood flow (see later). For this reason, the natural history of stable angina is determined largely by progression of the disease in the coronary arteries. The key to improving prognosis in these patients is meticulous management of the risk factors for atherosclerosis that include high cholesterol, diabetes, hypertension, obesity, and elimination of smoking. When symptoms become troublesome, patients are usually treated with β-adrenergic blockers and arteriolar vasodilators to reduce the heart’s energy demand, nitrates which decrease preload and dilate coronary collateral vessels, and drugs that
inhibit platelet aggregation and clotting in the diseased coronary arteries. Revascularization by coronary artery bypass surgery or angioplasty usually alleviates symptoms but has little or no ability to prolong survival.

Patients with coronary vasospasm typically experience angina when they are at rest, usually without a clear predisposing cause. This syndrome, which is also called vasospastic angina, variant angina, or Prinzmetal’s angina, is dangerous because, unlike demand angina in which myocardial energy starvation can be alleviated by rest, ischemia caused by vasospasm persists until the constricted coronary artery dilates. In some patients, myocardial ischemia lasts long enough to cause a myocardial infarction; in others, coronary vasospasm can trigger arrhythmias that may be fatal. The obvious goal of treatment is to relieve the coronary vasoconstriction, which can be done with variable success using combinations of nitrates, calcium channel blockers, and other vasodilators.

The pathophysiology of angina and its relationship to energy starvation explains the clinical picture in patients with unstable angina; the intensity of the symptoms increases, the amount of effort needed to evoke the chest discomfort decreases, and angina can occur at rest. The appearance of unstable angina usually indicates that the coronary occlusive disease is worsening but can also be caused when a complicating condition, like anemia, impairs oxygen delivery to the heart. Unstable angina typically follows a “stuttering” course because platelet plugs and thrombi that form in the damaged artery break up or dissolve, and then reappear. The resulting impairment of blood flow is often exacerbated by coronary vasospasm caused by vasoconstrictor substances that are released when platelets are activated by the damaged endothelium.

Instability is generally initiated by disruption of an atherosclerotic plaque, where damage to the fibrous cap in a previously stable coronary artery lesion exposes a thrombogenic surface that leads to arterial occlusion. The appearance of unstable angina has ominous prognostic implications as it can herald a myocardial infarction or sudden cardiac death. For this reason, unstable angina requires prompt medical attention.

Acute myocardial infarction occurs when coronary flow is reduced to levels so low as to cause myocardial cell death. Most clinical infarctions involve the left ventricle; right ventricular infarction can occur, but is less common. Because the endocardium is especially vulnerable to energy starvation (see earlier), coronary occlusion causes endocardial myocytes to be severely injured and to die sooner than those in the epicardium.

The criteria now used to classify patients with myocardial infarction depend on whether the ST segments in ECG leads facing the infarction are depressed or elevated. The distinction between STEMI and NSTEMI is determined largely by whether the full thickness of the ventricular wall or just the subendocardial layers are injured or infarcted (see later).

Prompt restoration of the normal balance between energy delivery and energy utilization is central to managing any of the acute coronary syndromes. Most important is to increase energy supply by addressing the underlying disease in the coronary arteries. This can be accomplished using aspirin and other platelet inhibitors, antithrombotic drugs, and thrombolytic agents. In patients with STEMI, the most effective treatment is reperfusion of the ischemic myocardium by immediate (primary) angioplasty. Reducing cardiac energy demands can also alleviate symptoms and improve prognosis, but this approach deals with the consequences, rather than the cause, of the clinical syndrome. β-Adrenergic blockers administered immediately after a coronary occlusion have important energy-sparing effects that are especially beneficial in regions where perfusion is reduced, but not totally abolished. Vasodilators, such as nitrates and calcium channel blockers, are useful because their ability to dilate arterioles that determine peripheral vascular resistance reduces afterload and so decreases energy demand. Nitrates also dilate veins, which has the added benefit of decreasing preload; these drugs also increase blood supply to ischemic regions of the heart by dilating intracoronary collateral vessels.

Interruption of coronary flow to the mammalian heart is followed within a few seconds by a decrease in contractility and profound impairment of ventricular filling (Fig. 17-2). The decrease in contractility, which is accompanied by abbreviation of systole, causes the ischemic region to bulge outward during systole because it cannot overcome the intraventricular pressure generated by the normally perfused myocardium. The resulting decrease in ejection also impairs filling because acute ventricular dilatation within the non-distensible pericardium reduces the ability of the heart to fill. This negative lusitropic effect, which is similar to pericardial tamponade, can be of greater hemodynamic importance than the negative inotropic effect.