Personalized accelerated physiologic pacing

Abstract

Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent with a high socioeconomic burden. Pharmacological heart rate lowering was recommended to improve ventricular filling in HFpEF. This article discusses the misperceptions that have resulted in an overprescription of beta-blockers, which in all likelihood have untoward effects on patients with HFpEF, even if they have atrial fibrillation or coronary artery disease as a comorbidity. Directly contradicting the lower heart rate paradigm, faster heart rates provide haemodynamic and structural benefits, amongst which lower cardiac filling pressures and improved ventricular capacitance may be most important. Safe delivery of this therapeutic approach is feasible with atrial and ventricular conduction system pacing that aims to emulate or enhance cardiac excitation to maximize the haemodynamic benefits of accelerated pacing. This conceptual framework was first tested in the myPACE randomized controlled trial of patients with pre-existing pacemakers and preclinical or overt HFpEF. This article provides the background and path towards this treatment approach.

Keywords: Cardiac filling pressures; Cardiac remodelling; Conduction system pacing; Diastolic function; Ejection fraction; Heart failure; Heart rate.

Figure 1

Effects of below normal heart rates on intracardiac haemodynamics. (A) Below normal heart rates lead to intracardiac congestion due to prolonged diastolic filling. The added blood volume is encountering opposing forces from the increasingly less compliant left ventricular myocardium, an effect that is disproportionally pronounced in hypertensive heart disease and heart failure with preserved ejection fraction. This increases both atrial and ventricular filling pressures and wall stress, which raises the risk for incident heart failure with preserved ejection fraction and atrial fibrillation. (B) Rightward shift of the pressure–volume loop with prolonged ventricular filling (rightloop). Left ventricular end-diastolic pressure (right lower corner of the loop) rises while following the end-diastolic pressure–volume relationship that is exponential in heart failure with preserved ejection fraction (dotted line). LVEDP, left ventricular end-diastolic pressure; LAP, left atrial pressure.

Figure 2

Height–heart rate relationship. (A) The human height and resting heart rate relationship. Linear regression of height and resting heart rate obtained from group medians of national survey and growth chart data. (B) Ranges of personalized heart rates (5th percentile, median, and 95th percentile) without consideration of ejection fraction in both women and men. (C) The modified personalized heart rate algorithm used in myPACE with an ejection fraction 50% pivot. (Personalized HR (b.p.m.) = (height [cm] × –0.3744) + 134.82) × √√ (ejection fraction [%]/50). A patient with an ejection fraction of 50% will be treated with a normal resting heart rate for their height to minimize the risk of ejection fraction reductions. At higher ejection fractions (>50%), patients are treated with incrementally higher heart rates to produce eccentric remodelling.

Figure 3

myPACE study design and flow. Pacemaker clinic patients at the University of Vermont Medical Center were consecutively screened. Those enrolled completed a Minnesota Living With Heart Failure Questionnaire, N-terminal pro-brain natriuretic peptide level, and a pacemaker interrogation. Patients were then randomized to a personalized pacemaker rate (myPACE) or remained at the nominal rate of 60 b.p.m. (Usual care) for 1 year. N-terminal pro-brain natriuretic peptide levels were repeated at 1 month and the Minnesota living with heart failure questionnaire was repeated at 1 month and 1 year. Pacemaker data and clinical outcomes were monitored continuously over the course of 1 year. NT-proBNP, N-terminal pro-brain natriuretic peptide.

Figure 4

Primary outcome of the myPACE randomized controlled trial.

Figure 5

Illustration of the main effects of personalized accelerated physiological pacing. The immediate haemodynamic benefits are followed by eccentric remodelling with a reduction in wall thickness and increased capacitance that improves left ventricular compliance and reserve capacity.