Chronotropic Incompetence: Causes, Consequences, and Management

Chronotropic incompetence (CI), broadly defined as the inability of the heart to increase its rate commensurate with increased activity or demand, is common in patients with cardiovascular disease, produces exercise intolerance that impairs quality of life, and is an independent predictor of major adverse cardiovascular events and overall mortality. However, the importance of CI is underappreciated, and CI is often overlooked in clinical practice. This may be due in part to multiple definitions, the confounding effects of aging and medications, and the need for formal exercise testing for definitive diagnosis. This review discusses the definition, mechanisms, diagnosis, and treatment of CI, with particular emphasis on its prominent role in heart failure (HF). CI is common and can be diagnosed by objective, widely available, inexpensive methods; it is potentially treatable, and its management can lead to significant improvements in exercise tolerance and quality of life. The ability to perform physical work is an important determinant of quality of life,1 and is enabled by an increase in oxygen uptake (Vo2).2 During maximal aerobic exercise in healthy humans, Vo2 increases approximately 4-fold.2 This is achieved by a 2.2-fold increase in heart rate (HR), a 0.3-fold increase in stroke volume, and a 1.5-fold increase in arteriovenous oxygen difference.2 Thus, the increase in HR is the strongest contributor to the ability to perform sustained aerobic exercise.3 It is therefore not surprising that CI can be the primary cause of or a significant contributor to severe, symptomatic exercise intolerance. HR at any moment in time reflects the dynamic balance between the sympathetic and parasympathetic divisions of the autonomic nervous system. Although the intrinsic rate of the sinoatrial node is approximately 100 beats per minute (bpm), resting HR in humans is generally much lower (60 to 80 …