Strategies for Aggressive Central Afterload Reduction in Patients With Heart Failure
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Change in Peak Oxygen Uptake (VO2) During Maximal Effort Exercise Stress Test According to Ejection Fraction Subgroups
研究概览
简要总结
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.
详细描述
Research Design and Methods
Hypotheses Knowledge of central aortic pressure waveforms (central pressure therapy, CPT) will affect the intensity of antihypertensive medication prescription, and treatment decisions based upon this knowledge in turn will lead to an enhanced reduction in CBP and AIx. Finally, it is hypothesized that this reduction in AIx/CBP will lead to improved exercise performance and LV systolic and diastolic reserve function.
Basic Study Plan This is a single-blind, randomized, controlled, parallel group intervention study examining the effects of a novel, noninvasive diagnostic test for determining AIx and CBP (SphygmoCor, Atcor Medical) on medical care, blood pressure control, exercise performance, and LV functional reserve in patients with chronic heart failure (HF) and systolic dysfunction (25%<EF<50%) and with preserved systolic function (EF>50%). Eligible subjects will undergo resting echocardiogram, noninvasive CBP assessment, and metabolic exercise stress testing on a recumbent cycle ergometer to quantify exercise performance. Echocardiography and CBP assessment will be performed at rest, during graded exercise, and immediately after peak exercise to determine indexes of LV systolic and diastolic performance and changes in CBP. Subjects will then be randomized (1:1) to subsequent determination of CBP at 1 month heart failure clinic visits versus sham (tonometry information acquired, but not shared with investigator). Investigators will then make adjustments to subject's medical therapy and antihypertensive regimen based upon the additional data procured via the Sphygmocor device. Subjects randomized to sham will have adjustments made as per standard clinical judgment based upon brachial blood pressure assessment and other clinical variables. In addition to standard clinical assessment, each subject will undergo 6 minute walk test at each visit, administered by the study coordinator.
At the 6 month follow up visit, subjects will undergo resting and exercise echo/CBP/metabolic stress testing exactly as performed at visit 1. The co-primary endpoints will be the change in central augmentation index (defined below) and change in peak oxygen uptake (VO2) from baseline. Secondary endpoints will include the changes in resting and exercise-induced CBP and brachial blood pressures, number of antihypertensive medications prescribed, resting and exercise change in LV systolic and diastolic function (see below), changes in: cardiac output, exercise time, anaerobic threshold, minute ventilation (VE) over carbon dioxide produced (VCO2) slope (ventilatory efficiency). There will be a total of 7 visits, the first and last for exercise testing; the intervening 5 visits will be routine heart failure clinic follow up appointments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
结局指标
主要结局
Change in Peak Oxygen Uptake (VO2) During Maximal Effort Exercise Stress Test According to Ejection Fraction Subgroups
时间窗: baseline, 6 months
Peak oxygen uptake (VO2) is the maximum rate of oxygen consumption as measured during incremental exercise, most typically on a motorized treadmill. Maximal oxygen consumption reflects the aerobic physical fitness of the individual. VO2 data was obtained via standard breath-by-breath expired gas analysis. Ejection Fraction Subgroups are based on participants reported at baseline.
Change in Aortic Augmentation Index (AIx) According to Ejection Fraction Subgroups
时间窗: baseline, 6 months
Aortic stiffness increases with aging, further augmenting cardiac load. One important repercussion of aortic stiffening is an increase in pulse wave velocity. As the outgoing pressure wave caused by ventricular ejection encounters zones of impedance mismatch, it is partially reflected backward, summing with the incident wave, to increase central aortic blood pressure. The magnitude of this systolic pressure wave reflection can be quantified by AIx. Aortic pressures were assessed in the seated position after 5 minutes rest. Aortic pulse waveform analysis was performed using a noninvasive, high-fidelity hand held tonometer placed over the radial artery. The built-in, custom software was then used to convert radial pressure waveforms to central aortic waveforms, which more accurately reflect LV afterload. The ratio of this augmented pressure to aortic pulse pressure is defined as the augmentation index (AIx).
次要结局
- Change in Heart Rate(baseline, six months)
- Change in Left Ventricle (LV) End Diastolic Volume(baseline, 6 months)
- Change in LV End Systolic Volume(baseline, 6 months)
- Change in LV Ejection Fraction(baseline, 6 months)
- Change in Stroke Volume(baseline, 6 months)
- Change in Mitral E Velocity(baseline, 6 months)
- Change in Mitral E/A Ratio(baseline, 6 months)
- Change in Mitral E Wave Deceleration Time(baseline, 6 months)
- Change in Brachial Systolic Blood Pressure (BP)(baseline, 6 months)
- Change in Brachial Diastolic BP(baseline, 6 months)
- Change in Central Systolic BP(baseline, 6 months)
- Change in Central Diastolic BP(baseline, 6 months)
- Change in Augmentation Index(baseline, 6 months)
- Change in Arterial Elastance(baseline, 6 months)