Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure
Completed · Not applicable
Conditions studied: Heart Failure
In brief
Heart failure (HF) is the leading cause of hospitalization among Americans over the age of 65 years, affecting greater than 5 million in the U.S. alone. Significant improvements in morbidity and mortality have been achieved through the use of medications that antagonize adverse neurohormonal signaling pathways, particularly therapies that reduce left ventricular (LV) afterload. Vascular stiffness increases with aging, contributing to the increase in cardiac load. One important repercussion of such stiffening is an increase in pulse wave velocity. As the incident pressure wave generated by cardiac ejection encounters zones of impedance mismatch (such as arterial bifurcations), part of the wave is reflected backward, summing with the incident wave, increasing central blood pressure (CBP). With normal aging, hypertension, and heart failure, increased wave velocity causes the reflected wave to reach the heart earlier, in mid to late systole, considerably increasing late-systolic load, impairing cardiac ejection, and diastolic relaxation in the ensuing cardiac cycle. The magnitude of this reflected pressure wave can be quantified by the augmentation index (AIx). The use of vasoactive agents which antagonize this increase in late systolic load (and AIx) may prove useful in the treatment of heart failure, by facilitating cardiac ejection during late systole when reflected pressure waves predominate. However, it has never been conclusively shown in humans that CBP-targeted therapy is useful in the management of HF. LV afterload, measured centrally in the ascending aorta, may differ considerably from brachial cuff-measured pressure, and has traditionally required invasive hemodynamic assessment to determine, limiting the applicability of techniques targeting CBP and late-systolic load. Recently, a novel, hand-held tonometer (SphygmoCor, Atcor Medical) has been developed for the noninvasive assessment of CBP. This pencil-like device is applied over the radial artery, and uses a validated mathematical transformation to derive central aortic pressure. This device has received FDA approval for clinical use in the assessment of central pressures. However, it remains unknown whether knowledge of CBP and late-systolic load (AIx) confers any clinically-significant incremental benefit in the management of patients with heart failure. The primary objective of the proposed investigation will be to determine if this assessment might have such a role.
Key facts
- Study ID
- NCT00588692
- Run by
- Mayo Clinic
- People needed
- 60
- Starts
- 2007-07-01
- Expected to finish
- 2012-12-01
- Last updated by the study team
- 2014-05-06
Who can join
Age: 18 and older. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- 18 years of age or greater
- Cardiac Ejection Fraction (EF) greater than or equal to 25% by echocardiography within 12 months
- Stable New York Heart Association (NYHA) class II or greater
- Heart Failure consultation within the last 18 months
- Ability to exercise on a cycle ergometer
- Stable angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) dosage for greater than 3 months
You may not qualify if…
- Enrollment in a concurrent study that may confound the results of this study
- Subjects with medical conditions that would limit study participation
- Pregnancy
- Brachial Systolic Blood Pressure less than 110 mmHg
- Baseline AIx less than 15%
- Cardiac Surgery with 60 days of potential study enrollment
- Myocardial infarction within 30 days of potential study enrollment
- Hemodynamically significant valvular stenosis (greater than mild)
- Heart failure due to thyroid disease
- Active myocarditis or anemia defined as hemoglobin less than 9 mg/dl
- Presence of severe renal insufficiency with serum creatinine greater than 2.5 mg/dl
- Significant pulmonary hypertension or Cor pumonale
- Irregular heart rhythms
- Dyspnea due to pulmonary disease
- Uninterpretable echocardiographic images or radial tonometry data
- Significant competing cause for exercise intolerance (e.g., severe stable angina)
Where it is running
- University of Arizona — Phoenix, Arizona, United States
- Mayo Clinic — Rochester, Minnesota, United States
Full record on ClinicalTrials.gov
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