Reductions in blood flow (and consequently the oxygen supply) to the myocardium can cause transient or permanent damage (ischemia and necrosis, respectively). Atherosclerosis of the coronary arteries is the most common cause. In most cases, the ischemia initially involves the subendocardial layers of the myocardium, which are characterized by a higher metabolic rate and oxygen consumption than the subepicardial layers since they more exposed to extravascular compressive forces (systolic tension, ventricular filling pressure). Only later does the damage extends to the full thickness of the myocardium (Fig. 11.1).

The main electrocardiographic (ECG) changes associated with myocardial ischemia involve the ST segment, the T wave, and the QRS complex. The nature and time-courses of these changes vary depending on the extension and temporal characteristics (acute vs. chronic, transient vs. persistent) of the ischemia and on the concomitant presence of other factors that can complicate diagnosis (bundle-branch blocks, pacemaker rhythms, WPW-type ventricular preexcitation).

Acute ischemia modifies the morphology and duration of the transmembrane action potential of the myocardial cells. Those of the subendocardial layers display decreases in the resting potential, the amplitude and velocity of phase 0, and the duration of the action potential (Fig. 11.2a). The result is an electrical gradient between ischemic and normal cells during the whole cardiac cycle. The ischemia may be caused by incomplete occlusion of a coronary vessel, in which case it will be confined to the inner layers of the myocardium (subendocardial ischemia), or by complete (transient or permanent) occlusion, in which case it will involve the full thickness of the myocardium (transmural ischemia).

The main ECG correlate of acute ischemia is displacement of the ST-segment from its normal position on the isoelectric line, which reflects the tendency of normal cardiomyocytes to repolarize in a uniform manner. In the presence of subendocardial ischemia, the leads “facing” the affected area record a depressed ST segment (Fig. 11.3). In contrast, transmural ischemia will be associated with ST-segment elevation in these leads and reciprocal ST-segment depression in the leads whose positive poles are oppositely directed (Fig. 11.4). Transmural ischemia can also produce significant changes in the T waves with the same electrical and clinical implications. The initial phase of ischemia is associated with an increase in voltage (T-wave peaking, referred to as hyperacute T-wave changes). It may be followed by ST-segment elevation and T-wave pseudonormalization (positivity of T waves that are negative under baseline conditions). Unlike the ECG changes that occur during subendocardial ischemia, those associated with transmural ischemia are closely correlated with the affected region of the myocardium.

Two different mechanisms have been proposed to explain ischemic elevation of the ST segment. The first assumes that the elevation is produced during electrical diastole, the ECG correlate of which is the TQ interval. In this case, the elevation is believed to reflect partial or complete depolarization of the ischemic cells, whose electrical charge is negative relative to their nonischemic counterparts, during phase 4 of the action potential. The result would be a flow of current (the so-called current of injury) represented by a vector directed away from the ischemic zone toward the nonischemic areas, which are positively charged during diastole. On ECG, these events would translate into TQ-segment depression (Fig. 11.5a) in the leads facing the ischemic zone. However, the electrocardiographs commonly used in clinical settings, which operate on AC power, automatically realign the TQ segment with the isoelectric line, thereby producing an apparent level change in the ST-segment, which is equal in magnitude and opposite in direction to the level change involving the TQ segment.

The second hypothesis assumes that the current of injury develops during electrical systole (Fig. 11.5b), which corresponds to the ST segment itself. It is based on the electrophysiological alterations in ischemic cells mentioned above (i.e., reduction of the resting potential, reduction of the amplitude and velocity of phase 0, and reduction of the overall duration of the action potential). These conditions result in an electrical current that flows from the nonischemic zone (where the cells are normally depolarized and therefore electronegative) toward the ischemic zone, which is prematurely repolarized or incompletely depolarized. The leads over the ischemic zone therefore record an elevation of the ST segment, which, as noted earlier, is often associated with reciprocal ST-segment depression in the opposite leads.

The phenomenon of ST-segment depression is caused mainly by delayed repolarization phase in the ischemic subendocardial zone. The ST-segment vector is therefore directed as usual from the epicardial to the endocardial layers, that is, from the nonischemic to the ischemic zone (Fig. 11.3). ST-segment depression is often associated with prolongation of the QT interval. The shape and appearance of the depressed ST segment is important: horizontal and down-sloping ST depressions of at least 1 mm are considered significant, whereas the significance threshold for up-sloping depressions is 1.5 mm (Fig. 11.6).

Chronically ischemic cells repolarize later than healthy cardiomyocytes because their action potentials are prolonged (Fig. 11.2b). The subepicardial zone recovers more slowly than the subendocardial myocardium: therefore, repolarization is represented by a T-wave vector moving from the epicardium to the endocardium. For this reason, the ECG alteration typical of this phase involves an inversion of T-wave polarity (from positive to negative) in the leads exploring the ischemic region (Fig. 11.7). Under these conditions, T-wave negativity in a given lead is generally associated with transmural ischemia in the area being explored by that lead.

The QRS-complex changes classically associated with myocardial necrosis appear in the post-acute phase of infarction and consist of “new” Q waves (not seen on previous recordings) with a duration of ≥40 ms and an amplitude at least one fourth that of the R wave in the same lead. It is important to recall that, in certain leads (the precordials in particular), Q waves can be physiological, reflecting septal depolarization. Pathologic Q waves will be found in two or more anatomically contiguous leads. This is especially true of lead III, where the appearance of Q waves is considered abnormal only if they are also present in leads II and aVF.

Q waves are a reflection of the necrotic tissue’s electrical inertness, that is, its inability to generate the electrical activity that would normally counterbalance similar forces originating in the opposite wall. The absence of electrical activity in a specific area results in the appearance of a QRS vector moving away from the necrotic zone and therefore inscribed as a negative deflection (Fig. 11.8). Abnormal Q waves were once considered a distinguishing feature of transmural myocardial infarctions. It has now become clear, however, that they may also develop in patients with nontransmural necrosis. Even more important, Q waves may well be absent in cases of transmural necrosis. As a result, myocardial infarctions are now electrocardiographically classified as Q-wave or non-Q-wave MIs. In the latter cases, the ECG alterations are confined to the ST segment and T wave. Phases of transient ischemia may also be associated with QRS alterations, mainly consisting of increased in amplitude and conduction disturbances. (Examples will be provided below in the section on angioplasty.)

It is important to stress that the ST-segment and T-wave changes that develop during ischemic heart disease (T-wave inversion in particular) may also appear in nonischemic forms of heart disease (left ventricular overload, myocarditis, pericarditis, hypertrophic cardiomyopathy), during certain types of drug therapy or electrolyte imbalances, and even in young persons (females in particular) with no significant heart disease. The saying that an ECG must first be described and then interpreted is never so true as in ischemic heart disease, and it becomes a valid basis for diagnosis only when analyzed within the specific clinical context of the case at hand. Failure to recall this rule can lead to misdiagnosis, sometimes with grave consequences.

The main clinical manifestations of coronary heart disease are stable angina pectoris and the acute coronary syndromes, which include unstable angina and myocardial infarctions (Q-wave and non-Q-wave forms). The different clinical pictures reflect specific characteristics of the endoluminal surfaces of atherosclerotic plaques in coronary arteries. In stable disease, the fibrous surface of a plaque tends to be smooth. The presence of ulceration triggers a chain of events, the most important of which is coronary thrombosis, which may be occlusive or nonocclusive. Stable angina is generally indicative of the presence of a soft plaque. Ulcerated plaques with thrombosis may be associated with myocardial infarction or unstable angina.