Rationale and design of the PACE HFpEF trial: Physiologic accelerated pacing as a holistic treatment of heart failure with preserved ejection fraction

Abstract

BackgroundIn heart failure with preserved ejection fraction (HFpEF), it has been assumed that pharmacologic heart rate suppression should provide clinical benefits through an increase in diastolic filling time. Contrary to this assumption, heart rate lowering in patients with preserved left ventricular ejection fraction and hypertension or coronary artery disease results in adverse outcomes and suggests that the opposite may be beneficial. Namely, shortening the diastolic filling time with a higher heart rate might normalize the elevated filling pressures that are the sine qua non of HFpEF. Initial clinical studies that assessed the effects of accelerated heart rates in pacemaker patients with preclinical and overt HFpEF provide support for this latter hypothesis, having shown improvements in quality of life, natriuretic peptide and activity levels, and atrial fibrillation burden.ObjectiveThe study sought to determine the effects of continued resting heart rate elevation with and without superimposed nocturnal pacing in HFpEF patients without standard pacing indication.MethodsThe physiologic accelerated pacing as treatment for heart failure with preserved ejection fraction (PACE HFpEF) trial is an investigator-initiated, prospective, patient-blinded multiple crossover pilot study that assesses the impact of accelerated pacing on quality of life, physical activity, N-terminal pro–B-type natriuretic peptide, and echocardiographic measures of cardiac structure and function.ResultsTwenty patients were enrolled and underwent dual-chamber pacemaker implantation under U.S. Food and Drug Administration investigational device exemption with both atrial and ventricular physiologic lead placement targeting the Bachmann bundle and the His bundle.ConclusionThis manuscript describes the rationale and design of the PACE HFpEF trial, which tests the safety and feasibility of continuous accelerated physiological pacing as a treatment strategy in HFpEF. In heart failure with preserved ejection fraction (HFpEF), it has been assumed that pharmacologic heart rate suppression should provide clinical benefits through an increase in diastolic filling time. Contrary to this assumption, heart rate lowering in patients with preserved left ventricular ejection fraction and hypertension or coronary artery disease results in adverse outcomes and suggests that the opposite may be beneficial. Namely, shortening the diastolic filling time with a higher heart rate might normalize the elevated filling pressures that are the sine qua non of HFpEF. Initial clinical studies that assessed the effects of accelerated heart rates in pacemaker patients with preclinical and overt HFpEF provide support for this latter hypothesis, having shown improvements in quality of life, natriuretic peptide and activity levels, and atrial fibrillation burden. The study sought to determine the effects of continued resting heart rate elevation with and without superimposed nocturnal pacing in HFpEF patients without standard pacing indication. The physiologic accelerated pacing as treatment for heart failure with preserved ejection fraction (PACE HFpEF) trial is an investigator-initiated, prospective, patient-blinded multiple crossover pilot study that assesses the impact of accelerated pacing on quality of life, physical activity, N-terminal pro–B-type natriuretic peptide, and echocardiographic measures of cardiac structure and function. Twenty patients were enrolled and underwent dual-chamber pacemaker implantation under U.S. Food and Drug Administration investigational device exemption with both atrial and ventricular physiologic lead placement targeting the Bachmann bundle and the His bundle. This manuscript describes the rationale and design of the PACE HFpEF trial, which tests the safety and feasibility of continuous accelerated physiological pacing as a treatment strategy in HFpEF.

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