Chronotropic incompetence across heart failure categories

The heart failure (HF) syndrome is characterized by an autonomic unbalance with sympathetic hyperactivity, which contributes to increased myocardial oxygen demand, oxidative stress, peripheral vasoconstriction, afterload mismatch with a progressive desensitization, and down-regulation of cardiac β1-receptors. These changes, together with a few other structural and peripheral changes, lead to chronotropic incompetence (CI), such as the inability to increase heart rate (HR) consistently with activity or demand. Chronotropic incompetence, regardless of the method and cut-off adopted to define it, is associated with reduced exercise capacity and a worse prognosis. Furthermore, different pharmacological classes might interfere with the physiologic exercise-induced HR response, thus generating some confusion. In particular, the β-blockers, albeit lowering peak HR, are known to improve prognosis and left ventricular inotropic reserve so that their withdrawal should be avoided at least in HF with reduced and mildly reduced ejection fraction. Similarly, a still debated strategy to counterbalance a blunted exercise-induced HR response is represented by rate-adapting pacing. The present review, besides supplying an overview on possible CI definitions, discusses the clinical impact of CI and potential pharmacological and non-pharmacological therapeutic strategies.