Mechanisms of Chronotropic Incompetence in Heart Failure With Preserved Ejection Fraction

Chronotropic incompetence is common in heart failure with preserved ejection fraction (HFpEF) and is associated with impaired aerobic capacity. We investigated the integrity of cardiac β-receptor responsiveness, an important mechanism involved in exertional increases in HR, in HFpEF and control subjects. Thirteen carefully screened patients with HFpEF and 13 senior controls underwent exercise testing and graded isoproterenol infusion to quantify cardiac β-receptor-mediated HR responses. To limit autonomic neural influences on heart rate (HR) during isoproterenol, dexmedetomidine and glycopyrrolate were given. Isoproterenol doses were increased incrementally until HR increased by 30 beats per minute. Plasma levels of isoproterenol at each increment were measured by liquid chromatography with electrochemical detection and plotted against HR. Peak VO and HR (117±15 versus 156±15 beats per minute;