Enhanced External Counterpulsation in Congestive Heart Failure: Possibly the Most Potent Inodilator to Date

John E. Strobeck, MD, PhD

Disclosures

CHF. 2002;8(4) 

Introduction

Enhanced External Counterpulsation (EECP) is a unique outpatient, noninvasive treatment method currently used to improve myocardial perfusion, reduce symptoms from obstructive coronary disease, and enhance patient functionality and quality of life. Its roots are in the science of intra-aortic balloon counterpulsation, but its effect on cardiac output and systemic vascular resistance, due to simultaneous venous and arterial sequential compression and simultaneous release, can be shown to be superior to the hemodynamic response typically seen with intra-aortic balloon counterpulsation. The device has undergone a significant evolution in design since the first units in 1953 used by Kantrowitz[1] and Amsterdam[2] and now, as used by the team from the University of Pittsburgh Medical Center in their paper in this issue of Congestive Heart Failure,[3] it is a streamlined system of external pneumatic cuffs, placed on the lower extremities and hips, sequentially inflated during early diastole, with careful online monitoring of the electrocardiogram, arterial pulse waveform/amplitude, and arterial oxygen saturation.

Lawson and colleagues[4] began reporting their experience in 1992 using EECP in chronic angina refractory to medical therapy and showed an overall improvement in stress myocardial perfusion in 78% of their patients exercised to the same cardiac workload. Post-treatment maximal stress testing showed an increase in peak exercise time and an increase in peak double-product in all patients with improved myocardial perfusion. These safety and efficacy results were extended in uncontrolled studies and confirmed by comparison with placebo in the Multicenter Study of Enhanced External Counterpulsation (MUST-EECP) completed and published in 1999.[5] Patients completing this trial were followed for 12 months after EECP treatment and demonstrated persistent improvement in health-related quality-of-life scores over placebo treatment.[6] An International EECP Patient Registry was begun in 1998 at the University of Pittsburgh Medical Center. Participation by EECP treatment centers was voluntary and during Phase I more than 5000 patients with angina pectoris were enrolled. Phase II has commenced and plans to enroll another 2500 patients with division into several important substudies such as type 2 diabetes, peripheral arterial disease, and sexual dysfunction in men.

Experienced EECP centers treating large numbers of patients with chronic obstructive coronary disease, including my own, have necessarily treated patients with low ejection fraction (EF) (<35%). Our experience, as documented by a recently published analysis of the International EECP Patient Registry data,[7] indicates that patients with low EF and obstructive coronary disease respond as well as patients with EF% >35% and do not suffer an increase of adverse events. The important study of Soran et al.[3] in this issue of Congestive Heart Failure extends these observations and forms the basis for a larger multicenter, randomized, single blind, controlled Prospective Evaluation of EECP in CHF (PEECH trial) currently enrolling patients in the United States.

Over the last two decades the preferred locus of care for patients with CHF has shifted from acute care inpatient settings to less-acute care inpatient and outpatient heart failure clinic settings. This shift has been in response to escalating inpatient health care costs while simultaneously attempting to improve access to care and outcomes of treatment. During the same time, the medical management of heart failure has become increasingly complex by virtue of: 1) trial results indicating the life-saving efficacy of several classes of medications and/or devices; and 2) the demonstrated preventive value of initiating treatment early in patients at high risk for heart failure and those with asymptomatic heart failure (see Table ).

The greatest challenges in managing symptomatic or refractory heart failure are: 1) obtaining objective data that signal disease progression or therapeutic effectiveness of specific treatment regimens; 2) inadequate dosing of medications with proven efficacy due to hypotension or bradycardia; 3) failure to detect the need for automatic implantable cardioverter-defibrillator/pacemaker insertion; and 4) poor patient compliance with polypharmacy regimens, salt/fluid intake, or scheduled follow-up leading to acute decompensations. Measurement of hemodynamic parameters such as cardiac output, contractility, systemic vascular resistance, and fluid content of the chest provide important information to augment medical decision-making, and is now possible noninvasively using impedance cardiography techniques.[9,10]

It is well known that the heart chambers, the vascular wall/endothelium, and systemic neurohormones are integrated in function to regulate the delivery of oxygen and blood to the tissues of the body. Disorders or altered reactivity of the vascular wall and/or endothelium can effect the delivery of oxygen regionally or systemically through release of vasoactive substances such as nitric oxide, endothelin, vascular growth factors, etc. Disorders of heart muscle function leading to CHF affect systemic oxygen delivery directly and indirectly through activation of neurohormonal systems (renin-angiotensin-aldosterone-system, sympathetic nervous system, and atrial natriuretic peptides), which exert their effects on both the heart and vascular wall/endothelium. Full activation of these systems in patients with systolic dysfunction typically creates a hemodynamic profile characterized by a low cardiac output, increased systemic vascular resistance, and increased intravascular fluid volume. Drug therapy that increases the heart's contractility by draining contractile reserves, reduces vascular resistance by inhibition of the renin-angiotensin-aldosterone system or the sympathetic nervous system, and reduces intravascular volume by causing diuresis will improve the CHF patient's hemodynamic profile but frequently creates an "over-medicated" state due to inadequate follow-up or reassessment of intravascular fluid status. This situation frequently leads to the development of renal dysfunction, further complicating therapy. There is currently no single oral medication treatment that is capable of increasing cardiac contractility, lowering vascular resistance, and increasing urine flow in patients with low EF. Additionally, the clinical efficacy of current medical therapy for CHF is maintained only while the medication is being taken. There is no long-term benefit to be obtained after short-term medical therapy for CHF.

EECP has been shown to have profound effects on central hemodynamics in patients with symptomatic or refractory left ventricular dysfunction. In our patients, already on optimal angiotensin-converting enzyme inhibitor, blocker, and diuretic therapy, EECP has increased cardiac output during treatment by more than 75%, reduced systemic vascular resistance by 20%-30%, and improved urine flow enough to restore diuretic responsiveness or allow diuretic dosage reduction. These changes in cardiac output and systemic vascular resistance are larger than any reported responses to oral or intravenous vasodilators or inodilators. EECP was shown to improve a load-independent measure of ventricular function, pre-load adjusted maximal power[11] indicating augmentation of intrinsic myocardial contractility. Additionally, EECP treatment increases nitric oxide production,[12,13] decreases endothelin levels,[14] increases vascular endothelial growth factor levels,[15] and decreases B-type natriuretic peptide levels[12] suggesting profound improvement in endothelial function, and a reduction of neurohormonal activation. Finally, EECP has demonstrated durable benefits in ischemic patients lasting for many multiples of the treatment duration.[6]

In summary, these results strongly suggest, in my view, that EECP (Vasomedical Inc., Westbury, NY) will play an important role as an adjunctive hemodynamic treatment for CHF. It can readily be used if the patient is hypotensive, bradycardic, or fatigued from other efficacious medication treatments. It can be used whether or not the patient has an arrhythmia or automatic implantable cardioverter-defibrillator/pacemaker. It enhances overall patient functionality as shown in the paper by Soran et al.[3] It should also help reduce poor patient compliance due to polypharmacy by reducing dosage or number of pills taken, and improve follow-up and disease process educational efforts by virtue of the need for daily visits for treatment. The results of the PEECH trial, currently in progress, are eagerly anticipated.

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