Enhanced External Counterpulsation in Patients With Heart Failure: A Multicenter Feasibility Study

Ozlem Soran, MD, Bruce Fleishman, MD, Theresa Demarco, MD, William Grossman, MD, Virginia M. Schneider, RN, Karen Manzo, RN, Paul-André de Lame, MD, Arthur M. Feldman, MD, PhD

Disclosures

CHF. 2002;8(4) 

In This Article

Methods

This study was an open, prospective, nonrandomized (single-group) feasibility trial involving three study centers. The study was supervised by a Steering Committee, and monitored by a Data Safety Monitoring Board. Anabase International Corporation (Stockton, New Jersey) performed data collection and management, statistical analysis and monitoring services. The study was conducted in compliance with the Declaration of Helsinki.

A total of 32 patients were enrolled in the study, 11 with idiopathic dilated cardiomyopathy and 21 with ischemic cardiomyopathy. Details of these patients are given in Table I and Table II . Informed consent was obtained from all patients prior to study enrollment. Six patients (four idiopathic, two ischemic) withdrew from the study prior to receiving therapy.

Patients of both sexes between the ages of 21 and 81 were eligible for the study if they had a diagnosis of heart failure (New York Heart Association [NYHA] class II or III) despite conventional therapy, left ventricular systolic dysfunction with an ejection fraction of 35% or less, the ability to exercise on a treadmill (Modified Naughton Protocol) with exertion limited by shortness of breath or fatigue, and clinical stability as demonstrated by an absence of medication changes over the 2 weeks prior to the first study visit. Patients were classified as having idiopathic cardiomyopathy if they had no hemodynamically significant coronary artery disease or other known causes of heart failure. Patients with heart failure and documented history of ischemic heart disease and/or diagnostic coronary arteriography were assumed to have ischemic cardiomyopathy.

Patients were excluded from the study if they met any of the following criteria: exercise limited by chest pain, electrocardiographic changes consistent with myocardial ischemia, or claudication; peripheral edema above the ankle; unstable angina; a serum digoxin level greater than 1.5 ng/mL; a serum creatinine level greater than 2 mg/dL; a myocardial infarction or coronary artery bypass grafting within the past 3 months; a cardiac catheterization within the past 2 weeks; acute myocarditis; a history of sudden death; the presence of an implantable cardioverter defibrillator or pacemaker; a history of clinically significant aortic stenosis, mitral stenosis, or aortic regurgitation; chronic obstructive pulmonary disease with forced expiratory volume at one second of 1.5 L or lower; coagulation abnormalities resulting in an international normalized ratio greater than 2.0; or severe hypertension. Because of the requirements for cardiac gating with EECP, patients were excluded if they had arrhythmias that would interfere significantly with triggering of the EECP device. In addition, patients were also excluded if they had a history of deep vein thrombosis, phlebitis, stasis ulcers, and/or pulmonary emboli, because of the potential risks associated with the use of pressurized cuffs around the lower extremities in such patients. Patients were also excluded from the study if they had any condition that precluded diastolic augmentation during initiation of EECP.

Heart failure treatment was optimized and stable prior to enrollment into the study. All patients were treated with an angiotensin-converting enzyme inhibitor unless contraindicated or not tolerated. In patients with ischemic heart disease, calcium channel blockers were permitted if unchanged for at least 1 month prior to the study. Likewise, blockers were allowed provided dosage had been unchanged for at least 6 months. In patients with idiopathic cardiomyopathy, calcium channel blockers were not permitted. Patients were excluded if a calcium channel blocker or a blocker had been withdrawn less than 3 months prior to the study.

Before treatment, patients were entered into a 2-week screening and baseline period, during which they underwent physical examinations, routine chemistry tests, and two baseline symptom-limited treadmill exercise tolerance tests. If the exercise tests differed by >20%, additional tests were performed; the average of two tests that were within a 20% range was used as the baseline value.

Each patient received 35 1-hour EECP sessions administered once a day, 5 days a week on average, for a total treatment period of 7 weeks. After assessing clinical stability, EECP was initiated and the inflation pressure applied was increased by 0.01 megapascals increments up to a maximum of 0.04 megapascals in all patients (0.04 MPa=300 mm Hg). Oxygen saturation during the treatments was measured by continuous pulse oxymetry. During the study, all drugs were kept as constant as possible, adjustments being made only when medically essential. Injected inotropic agents were not permitted.

Each patient was followed for a period of six months, with study visits at 1 week, 3 months, and 6 months after the end of the treatment period. All assessments performed at baseline were repeated at the 1-week and 6-month follow-up visits. In addition, a clinical assessment was made at the 3-month follow-up visit.

The primary study parameter was safety as reflected by adverse events experienced during the administration of EECP, adverse events during the overall treatment period, or changes in laboratory parameters. Other parameters included changes in exercise capacity and quality of life.

Statistical analysis was performed by comparing mean changes of the primary parameters from baseline to study visits at either 1-week post-EECP treatment or at the end of the study, using paired t tests.

Clinical examinations and laboratory parameters were summarized at each visit. Change and percent change from baseline are expressed using descriptive statistics (N, Mean, Standard Error, etc.). Paired t tests were used within each etiology of heart failure (ischemic or idiopathic) to test whether the change or percent change from baseline was significant.

Peak exercise parameters, Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores,[11] and NYHA status were summarized as described above. These were also analyzed using analysis of variance with etiology of heart failure, study site, and their interaction, as factors (if significant at the 0.15 level). The primary analysis was done using observed cases only and is presented here. A secondary analysis was done using the method of last observation carried forward for imputing missing data, and produced similar results.

Descriptive statistics were also used to summarize demographic variables, medical history, leg discomfort, worsening of condition, and area and pressure ratio. Adverse events were summarized within each etiology of heart failure by incidence, causal relation, intensity, relationship, and action taken.

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