Chronotropic Incompetence in Patients With HFpEF

Determinants of Chronotropic Incompetence in Patients With Heart Failure and a Preserved Ejection Fraction (HFpEF)

The purpose of this study is to determine the mechanisms of chronotropic incompetence (inability to increase heart rate with exercise) in patients with heart failure and preserved ejection fraction (HFpEF). The investigators will test both central command regulation and cardiac beta-receptor sensitivity over control of heart rate.

About half of all elderly patients with a diagnosis of congestive heart failure have apparently normal systolic function, so called "heart failure with a preserved ejection fraction" or HFpEF. To date, no effective therapy for HFpEF has been found, in part because of failure to discern key pathophysiologic pathways.

Although HFpEF is a complex disease with multiple pathophysiologic pathways leading to the phenotype of heart failure, virtually all proposed mechanisms involve some impairment of diastolic function - the inability of the heart to fill adequately at a low enough pressure to avoid congestion which during physical activity or exercise, prevent an increase in heart rate. A number of studies have purported the inability to increase heart rate (chronotropic incompetence) is responsible for the diminished exercise capacity.

Alternatively, the investigators hypothesize that the stiff, slowly relaxing heart of patients with HFpEF causes a marked elevation in pulmonary capillary pressure during exercise which leads to premature fatigue prior to achieving maximal heart rate, thus causing apparent "chronotropic incompetence".

Healthy Controls

Inclusion Criteria:

• ages > 60 years
• body mass index <30
• absence of co-morbid conditions including hypertension, diabetes, heart failure, asthma, chronic obstructive pulmonary disease, coronary artery disease as evidenced by angina or prior myocardial infarction or cerebrovascular disease as evidenced by prior transient ischemic attack or stroke

Exclusion Criteria:

• ages less than 60
• body mass index >30
• presence of co-morbid conditions including hypertension, diabetes, heart failure, asthma, chronic obstructive pulmonary disease, coronary artery disease as evidenced by angina or prior myocardial infarction or cerebrovascular disease as evidenced by prior transient ischemic attack or stroke
• Patients with chronic orthopedic injury that might make them unable to participate in an exercise testing will also be excluded
• Subjects unable to speak English will not be recruited because of the complex experimental studies and the need for precise communication between the volunteers and the research staff to ensure safety.

HFpEF Subjects

Inclusion Criteria:

• Patients will be > 60 years old, male or female, all races.
• signs and symptoms of heart failure
• ejection fraction > 0.50
• objective evidence of diastolic dysfunction.
• All patients must be in sinus rhythm without a left bundle branch block at the time of study

Exclusion Criteria:

• underlying valvular or congenital heart disease
• restrictive or infiltrative cardiomyopathy
• acute myocarditis
• New York Heart Association (NYHA) Class IV congestive heart failure, or heart failure that cannot be stabilized on medical therapy
• other condition that would limit the patient's ability to complete the protocol
• manifest ischemic heart disease
• Coumadin/warfarin therapy
• Patients with chronic orthopedic injury that might make them unable to participate in an exercise testing will also be excluded
• Subjects unable to speak English will not be recruited because of the complex experimental studies and the need for precise communication between the volunteers and the research staff to ensure safety.