ECG and Standard Exercise Stress Testing

Intraventricular Conduction Delays

Intraventricular conduction delays (IVCDs) and bundle branch blocks (BBBs) can be seen in patients without known cardiovascular disease (CVD) (isolated BBB) and in those with nonischemic or ischemic cardiomyopathies. Criteria for defining these conduction disturbances have been well established. Some patients with BBB will have rate-related or intermittent episodes of BBB, which may progress to permanent BBB over time.

In multiple studies, the presence of a right BBB (RBBB) has not been associated with an increased risk of overall mortality, cardiovascular mortality, or CVD. However, multiple population-based longitudinal studies have shown that the presence of a left BBB (LBBB) is associated with CVD including future high-grade atrioventricular block and increased cardiovascular mortality. More recently, these findings have been extended to patients with incomplete LBBB and nonspecific IVCD.

Despite these clinical findings, the presence of an RBBB and not an LBBB has been recently found to be associated with large anteroseptal scarring in patients with cardiomyopathy of both ischemic and nonischemic etiology. This is consistent with necropsy studies evaluating the blood supply of the conduction system. Whereas the right bundle is supplied solely by septal perforators originating from the left anterior descending artery, the left bundle has dual blood supply in 90% of cases with the septal perforators feeding the anterior fascicle of the left bundle and the right coronary artery feeding the posterior fascicle via the posterior descending artery ( Fig. 10.1 ). The anterior and posterior fascicles of the left bundle each have a dual blood supply in up to 50% of cases. For this reason, despite the common misconception, new complete LBBB is rarely seen as a complication of acute anterior infarction and, when seen, is usually indicative of massive infarction.

One of the most significant effects of IVCD in patients with coronary disease is the challenge that it presents with interpretation of acute ischemic changes and stress ECG changes. Stress ECG alone has a very poor diagnostic accuracy in the presence of LBBB. However, important prognostic information can still be gathered from exercise performance when combined with an imaging modality to evaluate for ischemia such as two-dimensional echocardiography or myocardial perfusion imaging. In one large single-institution experience, among patients with a positive exercise stress echocardiogram, those with underlying LBBB had a significantly higher future mortality rate than those with an RBBB or no conduction abnormality (4.5% per year vs 2.5% per year and 1.9% per year, respectively). Additionally, those patients with a normal stress echocardiogram showed a similar mortality with and without LBBB.

Whereas the presence of LBBB with known coronary disease clearly is associated with an increase in the risk of cardiovascular events, the presence of LBBB does not increase the probability of coronary disease itself. In a study of patients without known coronary disease referred for coronary computed tomography angiography (CCTA), 106 patients with presumed new LBBB were compared with 303 matched controls and found to have no significant difference in the presence of obstructive coronary disease. This study also found comparable image quality in LBBB patients and non-LBBB controls, suggesting that CCTA is a reasonable diagnostic test in patients with LBBB.

The clinical scenario most often seen in chronic coronary patients is a new-onset BBB in the absence of symptoms. There are no consensus guidelines for how these patients should be evaluated. The evidence would suggest that the most likely etiology is a chronic degenerative/fibrotic process affecting the conduction system rather than new ischemia. However, it may be reasonable to consider noninvasive evaluation of cardiac function and in selected patients, screening for ischemia. Additionally, increasing the frequency of routine ECG testing is also reasonable.

Ventricular Ectopy

Patients with stable CAD are often found to have premature ventricular ectopic beats (PVCs) on routine ECG. Most times these are asymptomatic; however some patients will experience palpitations. In patients with a low burden of ectopy and no symptoms, medical therapy should not be changed from that recommended for the coronary disease itself. Attempts to suppress ectopy with arrhythmic drugs should be avoided in these patients based on the results of the Cardiac Arrhythmias Suppression Trial (CAST). For patients with minor symptoms, starting or increasing dosages of β-blockers or calcium-channel blockers should be considered.

Patients with high burdens of ventricular ectopy may have decreased systolic function. An exact burden cutoff has not been elucidated to date; however studies have shown that a range of PVC burden from 13% to 24% of total beats is independently associated with development of cardiomyopathy. In addition, successful elimination of the ectopy through ablation can result in significant improvement and even normalization of systolic function. The link between a high burden of ectopy and cardiomyopathy has been extended to patients with chronic coronary disease. In a small single-center study of patients with CAD and high ectopy burden, PVC ablation decreased PVC burden from 22% to 2.6%. The mean left ventricular ejection fraction (LVEF) improved in these patients from 38% to 51%, significantly better than in a control population without ablation that showed no change in systolic function. This more aggressive strategy may eliminate the need for implantable cardioverter-defibrillators (ICDs) in some patients. In a study of 66 patients (including 11 with known coronary disease) undergoing PVC suppression with ablation who met current guidelines for ICD implantation before therapy, 64% no longer had an indication based on improvement in LVEF (including 10 of the 11 patients with prior myocardial infarction).

Whereas most patients with PVCs should still be managed based on symptoms only, further attention should be paid to the patient with very frequent ventricular ectopy. Evidence shows these patients are at higher risk of developing cardiomyopathy and that elimination of the ectopy can reverse left ventricular dysfunction, even among those with an ischemic etiology. As there are no specific guidelines addressing management of PVCs in patients with CAD, we recommend ambulatory Holter monitoring and assessment of LV function in patients with a high burden of ectopy by history or ECG.

Persistent and New Q Waves

As mentioned previously, ECGs should be obtained at baseline and at regular intervals in patients with chronic CAD. CAD patients will often have evidence of prior infarction or conduction system disease at baseline. These baseline ECGs are important to use as a comparison when patients present with new symptoms.

Pathologic Q waves are considered the classic ECG sign of necrotic myocardium and are seen in the late progression of myocardial infarction (MI). In the modern era of reperfusion therapy however, many patients who are found to have Q waves on presenting ECGs can have partial or complete resolution over time. Compared with patients with persistent Q waves, those with eventual Q wave regression have significantly improved LVEF ( Fig. 10.2 ).

When routine ECGs are performed in patients with coronary disease, occasionally one will find evidence of new MI in patients who have had no apparent symptoms. This evaluation and management of apparent “silent” MI is not directly addressed in current practice guidelines. Clearly a careful history should be obtained, focusing on symptoms that may have been atypical for the patient and symptoms that may point to crescendo angina or congestive heart failure. In our opinion, in the absence of symptoms the finding of new Q waves on routine ECG does not require an evaluation for ischemia, but should trigger consideration for reassessment of LV function. This is particularly true for patients who have not yet met criteria for an ICD as a new infarction may now place them at increased risk of sudden death. If new LV dysfunction is seen, it is reasonable to consider an assessment for ischemic and viable myocardium even in the absence of symptoms, as revascularization may improve LV function.

Many other ECG abnormalities may be seen, from nonspecific ST changes to LV hypertrophy, which have been associated with increased risk of coronary events in the non-CVD and hypertensive populations. The potential effect on long-term prognosis in patients already diagnosed with coronary disease is not well understood. However, given that each of these findings alone changes classic risk models only modestly, it is unlikely that these findings in patients with known coronary disease on optimal medical therapy significantly modifies their future risk of coronary events. It is again our opinion that these findings should trigger a reevaluation of potential symptoms and possibly a reassessment of LV function.

Historical Perspective

In 1941 Masters and Jaffe reported the combination of Masters’ two-step stress test with the ECG to obtain objective evidence of angina pectoris. Because many patients could not perform the Masters two-step stress test, Bruce and colleagues devised a more accessible version of the stress test using the motorized treadmill with inclination in 1956. His eponymous protocol has been included in over 15,000 scholarly articles and remains the most common and most studied protocol today.

More definitive diagnostic procedures and treatment were developed soon afterward. Coronary angiography was introduced in 1958 and coronary artery bypass (CABG) surgery in 1967. Since the early days of stress testing, other modalities of imaging have accompanied stress ECG, especially myocardial perfusion imaging and echocardiography. The combination of imaging with the stress ECG has improved the sensitivity and specificity of the test (see Chapter 11, Chapter 12, Chapter 15 ). Categorically, these are functional or physiologic tests that depend on their ability to produce objective evidence of myocardial ischemia.

The objectives of stress ECG need to be evaluated in the context of a cost-sensitive environment. The first consideration is the diagnostic value of determining obstructive CAD, more precisely the confirmation that a patient’s symptoms of chest discomfort are due to angina pectoris. The second is risk stratification and the prognostic value of stress ECG. The stress ECG may appropriately identify patients at high risk for MI and other major adverse cardiac events. Thus the clinician may better determine which patient might derive incremental benefit from revascularization. Finally, one may use stress ECG to objectively determine the efficacy of a treatment regimen whether it is revascularization or medical therapy.

This section will describe the role of stress ECG in CAD; it will also review the physiology of exercise and the pathophysiology of myocardial ischemia and describe the performance of the test and the interpretation of its outcomes.

The Physiology of Exercise

Exercise, and for that matter any activity that requires the contractions of muscles, requires energy. This energy is predominantly derived from oxidative metabolism to generate adenosine triphosphate. Fundamentally, the process requires efficient delivery of oxygen to the tissues. At any moment, the total body uptake of oxygen is defined as VO ₂ . The Fick equation describes the relationship between cardiac output (CO) and the extraction of oxygen at the tissue level (arteriovenous oxygen difference). VO ₂ = CO × a–vO ₂ difference.

The VO ₂ , or total body oxygen requirement at rest, is described as 1 MET (metabolic equivalent). This is estimated at 3.5 mL O ₂ /kg body wt. per min. Thus any physiologic activity or exercise can be described as a multiple of this basal metabolic unit. Whereas 1 MET corresponds to complete rest, 5 METs of energy is the equivalent of walking one block or climbing one flight of stairs.

During exercise, VO ₂ increases. In other words, the person who is exercising requires more oxygen to supply energy for exercising muscles. In order to accomplish this, CO (the product of heart rate [HR] × stroke volume) may increases fourfold to sixfold, HR may increase twofold to threefold, and stroke volume may increase by 50%. At approximately 40% of maximum VO ₂ the increase in stroke volume plateaus due to a progressive decrease in diastolic filling time. By definition, VO ₂ max is the maximum achievable VO ₂ and is related to age, sex, physical fitness, and cardiac status. O ₂ extraction in the periphery may increase as much as threefold during exercise, and the maximum O ₂ extraction is estimated at 15–17 mL O ₂ /100 mL blood as the physiologic limit. VO ₂ peak describes the symptom-limited maximum of a given patient undergoing exercise while testing and is commonly expressed as the patient’s maximum exercise capacity or aerobic limit.

Aerobic exercise (high-repetition/low-resistance exercise) involves vigorous muscle activity (multiple cycles of muscular contraction and relaxation). Oxidative metabolites are generated in these large working muscles. The metabolites cause dilation of local arterioles, which increases the blood flow to the exercising muscles up to fourfold. Massive dilation of these vessels decreases vascular resistance, which contributes to the increase in stroke volume. With upright exercise such as jogging or fast walking, large muscle groups lead to an increase in sympathetic tone and a relative decrease in vagal tone. This increase in sympathetic tone increases HR and myocardial contractility. This also causes a shunting of blood from the renal, splanchnic, and cutaneous vascular beds supplying large muscles. This circulatory shunting increases the venous return and further contributes to an increase in CO through the Starling mechanism. During exercise, systolic pressure increases gradually, driven by an increase in CO, and diastolic pressure remains constant or decreases slightly.

Dynamic arm exercise results in a similar hemodynamic response but HR and systolic blood pressure tend to be higher. During exercise, the myocardium experiences a marked increase in oxygen demand. This demand is driven by HR, blood pressure, LV contractility, wall thickness, and cavity size. The rate–pressure product (maximum HR × maximal systolic blood pressure achieved during exercise) is an excellent index of the O ₂ demand (see Chapter 6 ). Myocardial ischemia develops when the demand for oxygen is not met. The main goal of stress testing is to elicit myocardial ischemia under a controlled condition.

Subject Preparation

Perhaps the most important aspect of stress testing is patient selection. As discussed in more detail in the next section, stress testing performs optimally as a diagnostic test when patients with intermediate likelihood of disease are selected ( Box 10.2 ). Furthermore, the patient must be physically capable of performing treadmill exercise and the ECG must be interpretable for ischemic changes.

The most common forms of stress testing are the graded motorized treadmill and the cycle ergometer (stationary bicycle). The cycle ergometer is more commonly used outside the United States; it has the advantage of less expense and requires less laboratory space. Furthermore the cycle ergometer allows for easier access to the patient’s arms and torso for measuring blood pressures and recording the ECG during exercise. However, subjects inexperienced in cycling tend to fatigue before they reach their true VO ₂ max due to leg fatigue. Inexperienced subjects achieve 10% to 20% lower VO ₂ max on the cycle ergometer than on treadmill exercise. Dynamic arm exercise is another variety of aerobic stress available for patients who cannot perform adequate leg exercise; however, this modality is rarely used in clinical practice ( Box 10.3 ). The graded treadmill is the most common modality used in the United States. There are a variety of protocols available, but the Bruce protocol ( Table 10.2 ) is by far the most common and best studied protocol in practice today.

Most people can perform the Bruce protocol stress test. Some individuals have never exercised on a treadmill. A brief demonstration of the treadmill exercise is highly recommended before allowing a patient to initiate the test.