![]() ![]() Participants arrived in a climate-controlled laboratory after eating a light breakfast or lunch. Atrioventricular–nodal blocking agents (eg, nondihydropyridine calcium channel blockers, β-blockers) were held for at least 5 half-lives before testing days. Both HFpEF and senior participants underwent a screening maximal exercise stress echo test before enrollment and were excluded if they had evidence of coronary ischemia by ECG and echocardiography. Control participants were excluded if they had a history of hypertension or elevated 24-hour ambulatory BP >140/90 mm Hg (Oscar 2 Suntech Medical) and if they had a history of cardiovascular disease (eg, stroke, myocardial infarction, atrial fibrillation), diabetes, chronic obstructive pulmonary disease, former or current smoking, or body mass index >30 kg/m 2. 5Īfter providing written informed consent, all participants underwent testing as outlined in the following. Control participants were recruited from the Dallas Heart Study, a population-based cohort of >6000 individuals, enriched by a random sampling of employees of Texas Health Resources, a large health care provider in the Dallas–Fort Worth metroplex, as previously described. Patients with HFpEF were excluded for history of ejection fraction 40 kg/m 2, serum creatinine level >2.0 mg/dL, severe chronic obstructive pulmonary disease, permanent atrial fibrillation, constrictive or restrictive cardiomyopathy, severe valvular disease, or history of valvular surgery and if they were unable to perform exercise testing. Patients were invited to participate if they were older than 60 years, had a hospitalization for heart failure, had evidence of congestion by either chest x-ray or elevated filling pressures (pulmonary capillary wedge or left ventricular end-diastolic pressures >16 mm Hg), and had left ventricular ejection fraction >50% at study entry. ![]() The institutional review boards of the University of Texas Southwestern Medical Center and Texas Health Resources approved all study procedures. Patients with HFpEF were recruited from a university cardiology clinic. We hypothesized there would be no differences in central command feedforward control of heart rate but that skeletal muscle metaboreceptor function would be augmented compared with senior controls of similar age. We used a static handgrip exercise model 4 to assess integrity of central command (maximal heart rate during isometric handgrip) and muscle metaboreceptor (blood pressure during postexercise circulatory arrest) reflexes. The purpose of this study was to assess the integrity of autonomic control over exercise heart rate, specifically central command and skeletal muscle metaboreceptor function, and whether abnormalities in either of these reflexes could account for apparent chronotropic incompetence in HFpEF. 3 Whether upstream autonomic signaling pathways are also impaired in HFpEF is unknown. We have previously shown cardiac β-receptor transduction is impaired in patients with HFpEF, although this impairment does not fully explain the reduced peak heart rate in these patients. 2 These signals are then transduced at the sinus node to electromechanically increase heart rate and cardiac contractility. Mechanisms controlling heart rate responsiveness during exercise are regulated by afferent feedback from muscle metaboreceptors and mechanoreceptors, which are integrated with feedforward signals from higher motor cortical centers in the central nervous system (central command) to decrease parasympathetic and increase sympathetic output. A blunted heart rate response limits increases in cardiac output, which in turn reduces peak oxygen uptake (V o 2). 1 One purported mechanism of decreased exercise capacity is chronotropic incompetence: the inability to increase heart rate during exercise. Several purported mechanisms involving cardiac and peripheral pathways are thought to play a role in limiting exercise capacity in these patients by impairing convective or diffusive oxygen delivery. Customer Service and Ordering InformationĮxercise intolerance is common in patients with heart failure with preserved ejection fraction (HFpEF).Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).
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