Should Early Acceleration of Heart Rate During Exercise Be Used to Risk Stratify Patients With Suspected or Established Coronary Artery Disease

Exercise is one of the most common noninvasive stressors used to risk stratify patients with suspected or established coronary disease. Functional capacity, time to onset of demand-induced ischemic ST-segment shifts or angina, complex ventricular arrhythmias, a progressive fall in systolic blood pressure during exercise, and abnormal heart rate (HR) responses either during or after exercise are all well-established independent predictors of long-term outcome and, when used in combination, have the potential to identify prognostic high-risk patients who may be candidates for coronary angiography and coronary revascularization.1 Among HR variables tested that are predictive of mortality, the most common include the ability to augment HR to age-predicted maximum (chronotropic response), the HR recovery response in the immediate postexercise phase, and the ST-segment response corrected for HR. 2,3 Article p 468 A normal increase in HR during exercise and the ability to slow HR in the immediate postexercise phase are dependent on the autonomic nervous system and the ability of the cardiac conduction tissue to normally propagate the electrical impulse. The vasomotor center, located in the reticular substance of the medulla and pons, has the capability to transmit parasympathetic impulses through the vagus nerves to the heart that slow HR and can modulate excitatory impulses through the sympathetic nervous system that increase HR and contractility.4 Regulation of the vasomotor center is affected by higher nervous centers that can excite or inhibit the center, as well as by circulatory reflexes initiated by aortic arch and carotid sinus baroreceptors that stimulate the vagal parasympathetic center. During the early phases of exercise in normal subjects, increased HR is mediated predominantly by decreased parasympathetic tone and in the later stages of exercise by a marked increase in sympathetic tone and circulating catecholamines. Thus, an exaggerated initial HR response to exercise (eg, first 1 to 2 minutes of exercise) could signal autonomic dysfunction, a condition associated with increased mortality. In 2005, Falcone et al5 published a report in Circulation indicating that a rapid HR increase at the onset of exercise (HR 1 minute 12 bpm) predicts increased adverse cardiac events and cardiovascular mortality in patients with coronary artery disease even after adjustment for potential prognostic confounders. This finding is important because the observation would allow potential risk stratification of patients after only 1 minute of exercise, a useful parameter for patients who cannot perform more strenuous exertion. Notably, the authors comment that their findings require validation in a separate data set. In this issue of Circulation, Leeper et al6 examined initial HR responses using multiple different definitions, including HR15 seconds, HR2 METS,, and HR1 minute, and report that a rapid initial increase in HR predicts decreased total and cardiovascular mortality and that peak exercise HR is the most powerful predictor of cardiovascular prognosis after adjustment for prognostic confounders. How can both welldone studies reach the exact opposite conclusions? A careful analysis provides useful insight. The exercise protocol that Falcone et al 5 used was a symptom-limited semisupine bicycle ergometer with an initial workload of 25 W and fixed stepwise 25-W increments every 2 minutes. The 458 patients were selected for exercise testing after a cardiac catheterization had been performed and coronary disease confirmed. Presumably, patients with highrisk coronary disease were excluded from the study and referred for revascularization. -Blockers and calcium antagonists were withdrawn before testing in 69% of subjects. Patients with signs or symptoms of heart failure, with impaired left ventricular ejection fraction, on digitalis, with evidence of valvular or congenital heart disease, and with a pacemaker or noninterpretable ECG were excluded from the study. Patients were followed up for a median of 6 years, and the cardiovascular end points tested were a composite of cardiac death (n15) and nonfatal myocardial infarction (n56). The overall mortality was very low (3.3% after a median of 6 years), indicating a low-risk population of patients with coronary artery disease.