Role of heart rate in coronary artery disease
Heart rate: a key determinant of myocardial ischemia
Stable angina is the presenting symptom in approximately 50% of patients with coronary artery disease.1 In Europe and the United States, 30 000 to 40 000 patients per million people suffer from chronic stable angina. Angina occurs when myocardial perfusion is unable to meet the metabolic demand. Heart rate influences both the myocardial oxygen demand as well as the supply. Heart rate is known to be the most important determinant of myocardial oxygen demand, and thereby a primary determinant of cardiac work and of the metabolic requirements of the heart.2,3 Increased heart rate also leads to shortening of diastole. Since myocardial perfusion occurs predominantly during diastole, decreased diastolic time can decrease myocardial perfusion in the subendocardial layers thereby increasing myocardial ischemia. Increased heart rate can also induce coronary constriction and worsen the hemodynamic consequences of coronary artery stenosis.4
Most episodes of ambulatory or exercise-induced myocardial ischemia in stable coronary patients are preceded by an increase in heart rate.5,6 The likelihood of developing ischemia is related to the baseline resting heart rate as well as to the magnitude and duration of the increase. The incidence of ischemic episodes doubles when the heart rate increases from 60 to 80 beats per minute (bpm) in patients with significant coronary narrowing (Figure 1).7 Most episodes of asymptomatic ischemia are also preceded by an increase in heart rate.8
Figure 1. The likelihood of ischemic episodes increases with increasing heart rate.7
Thus reducing resting heart rate and limiting the increase in heart rate are a very rational strategy to prevent ischemia. Traditionally, heart rate reduction has been effectively used to relieve angina symptoms and ischemia. Heart rate reduction has been shown to be the primary mechanism by which β-blockers confer benefit in coronary artery disease. Reversal of β- blocker–induced reduction in heart rate has deleterious effects even on ventricular function (Figure 2).9
Figure 2. Benefits of β-blockade on LV function are attenuated or reversed by increasing the heart rate.9
All these findings clearly demonstrate that elevated heart rate is a key determinant of ischemia and cardiac function.
References
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2. Braunwald E. Control of myocardial oxygen consumption: physiologic and clinical considerations. Am J Cardiol. 1971;7:416-432.
3. Collins P, Fox KM. Pathophysiology of angina. Lancet. 1990;1:94-96.
4. Nabel EG, Selwyn AP, Ganz P. Paradoxical narrowing of atherosclerotic coronary arteries induced by increases in heart rate. Circulation. 1990;81:850-859.
5. Hinderliter A, Miller P, Bragdon E, et al. Myocardial ischemia during daily activities: the importance of increased myocardial oxygen demand. J Am Coll Cardiol. 1991;18:405-412.
6. Panza JA, Diodati JG, Callahan TS, et al. Role of increases in heart rate in determining the occurrence and frequency of myocardial ischemia during daily life in patients with coronary artery disease. J Am Coll Cardiol.1992;20:1092-1098.
7. Andrews TC, Fenton T, Toyosaki N, et al. Subsets of ambulatory myocardial ischemia based on heart rate activity. Circadian distribution and response to antiischemic medication. The Angina and Silent Ischemia Study Group (ASIS). Circulation. 1993;88:92-100.
8. Stone PH, Gibson RS, Glasser SP, et al, and the ASIS Study Group. Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Circulation. 1990;82:1962-1972.
9. Simon D.R. Thackray, A Justin M, et al. The effect of altering heart rate on ventricular function in patients with heart failure treated with beta-blockers. Am Heart J. 2006;152:713.e92713.e13.