Hypertrophic Cardiomyopathy Clinical Trial

Reduced Contractile Reserve: a Therapeutic Target in Heart Failure With Preserved Ejection Fraction(HFpEF)

Summary

Heart failure with preserved ejection fraction (HFpEF) accounts for over 50% of heart failure cases in the United States, affecting a primarily elderly population. No treatment has been shown to affect mortality in HFpEF, which is more than 50% at five years a hospitalization. This project explores the underlying cardiovascular physiology of patients with HFpEF with the goal of identifying new therapeutic targets that would allow improved treatment of this devastating disease.

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Full Description

Heart failure with preserved ejection fraction (HFpEF) is a difficult disease to diagnose due to nonspecific symptoms and clinical findings. The disease occurs in the elderly, who often have other illnesses and signs of aging that make diagnosis of heart failure more difficult. Recently, it has been suggested that HFpEF, which has primarily been thought to be a diastolic disease, is in fact multifactorial, with elements of abnormal systolic function and increased vascular stiffness playing a role in disease pathology. No treatment has been shown to reduce the high mortality of the disease. However, few studies have evaluated this population of patients during periods of increased physiologic stress, despite the consistent clinical presentation of impaired exercise tolerance with few symptoms at rest. This study explores the multifactorial physiology of HFpEF, with a detailed investigation of the specificity of abnormalities in contractile reserve and vascular stiffness for this disease, and exploration of the modifiability of these abnormalities. The techniques used are non-invasive, involving echocardiographic evaluation of cardiac function, and measurement of arterial stiffness using tonometry. The first aim of the study is to explore the specificity of a potential diagnostic test for HFpEF by investigating the change in ejection fraction before and after β-adrenergic stimulation with low-dose dobutamine in HFpEF compared to other groups important to distinguish clinically, specifically patients with shortness of breath due to pulmonary disease, and those with hypertension and left ventricular hypertrophy without clinical heart failure. In the second aim, the study will investigate the ability of the calcium channel blocker, amlodipine, to restore normal contractile responses of the myocardium. In the third aim, the role of arterial stiffness in drug responses in HFpEF will be explored. It is anticipated that improved understanding of the complex physiology of this multifactorial disease gained through this study will lead to more rational design of large clinical trials studying promising agents for HFpEF that impact not only diastolic function, but contractile reserve and arterial properties as well.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Male or female; Age 18 or older.
Left ventricular ejection fraction ≥ 50%.
Symptomatic heart failure or appropriate comparator group criteria
Informed consent signed by the subject

Exclusion Criteria:

Symptoms of active ischemia.
Moderate or severe mitral or aortic stenosis, or severe aortic insufficiency.
Serum creatinine > 3.0 or chronic hemodialysis.
Known chronic hepatic disease; defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels > 3.0 times the upper limit of normal as read at the local lab.
Severe renal dysfunction, i.e. glomerular filtration rate (GFR) <30 ml/min.
Atrial fibrillation
Myocardial infarction within the last year
Coronary bypass surgery within the last 6 months
Stroke within the last 6 months
Known aortic aneurysm
Contra-indication to withdrawal of beta blocker or antihypertensive medications
Resting or orthostatic hypotension (SBP < 90 mmHg)
Any gastrointestinal disorder which would interfere with drug absorption
Any significant valvular heart disease, including prior multiple valve replacement.
Pericardial Disease
Infiltrative or hypertrophic cardiomyopathy
Cor pulmonale
Unstable coronary disease
Pregnancy
Any condition which may prevent the subject from adhering to the study protocol, as determined by the investigator

Heart Failure with Preserved Ejection Fraction

Clinical evidence of heart failure with preserved ejection fraction, as manifest by at least 2 symptoms or signs, including dyspnea on exertion or at rest, orthopnea, jugular venous distention or hepatojugular reflux, rales or edema.
Controlled systolic BP (< 150 mmHg on the day of study)

Pulmonary Disease Group

Known obstructive airways disease with objective documentation of an isolated obstructive defect by pulmonary function testing.
No history of heart failure.
No history of cardiovascular disease, with the exception of hypertension or hyperlipidemia
History and physical examination free of signs and symptoms of heart failure, including elevated jugular venous pressure, hepatojugular reflux, rales or edema.
Baseline echocardiographic examination without evidence of heart failure, including systolic dysfunction of the LV or RV, or evidence of more than mild diastolic dysfunction on non-invasive assessment.

HTN/LVH Group

Known history of hypertension.
Echocardiographic evidence of left ventricular hypertrophy and diastolic dysfunction.
No history or physical examination evidence of heart failure, including excessive dyspnea on exertion, dyspnea at rest, orthopnea, PND, jugular venous distention, hepatojugular reflux, rales or edema.

Study is for people with:

Hypertrophic Cardiomyopathy

Estimated Enrollment:

14

Study ID:

NCT01354613

Recruitment Status:

Completed

Sponsor:

University of Wisconsin, Madison

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There is 1 Location for this study

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UW - Madison
Madison Wisconsin, 53705, United States

How clear is this clinincal trial information?

Study is for people with:

Hypertrophic Cardiomyopathy

Estimated Enrollment:

14

Study ID:

NCT01354613

Recruitment Status:

Completed

Sponsor:


University of Wisconsin, Madison

How clear is this clinincal trial information?

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