Safety and Feasibility of a Nocturnal Heart Rate Elevation—Exploration of a Novel Treatment Concept

Abstract

Diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) are associated with myocardial fibrosis and concentric left ventricular hypertrophy (LVH). In a preclinical model of LVH, we demonstrated that a moderate increase in heart rate can reduce interstitial fibrosis and improve LV compliance. We therefore hypothesized that moderately elevated heart rates can be used to beneficially modify the myocardial substrate in patients with diastolic dysfunction and HFpEF. As a preliminary step to test this hypothesis, we evaluated if patients can tolerate this novel pacemaker-based treatment approach without adverse effects. A pacemaker-mediated increase in heart rate to 100 beats/min for 5 hours at night was tested over 4 weeks in 10 patients with diastolic dysfunction. The patients underwent a physical examination, biomarker collection, 6-minute walk test, heart failure questionnaire, and echocardiography before and after the pacing intervention. None of the patients reported any symptoms at night. No arrhythmias were induced. Eight patients completed the protocol. Three patients experienced unanticipated daytime pacing from an interfering pacemaker function. There were no detrimental changes in biomarkers or LV systolic function. Nocturnal pacing at a rate of 100 beats/min appears to be safe and well tolerated in this small exploratory patient cohort.