Clinical Studies

The publications listed below will provide you a great start in understanding the benefits, mechanisms of action, and long-term outcomes of RejuvaHeart™ therapy.

Key Mechanisms of Action

Hemodynamic Effects of RejuvaHeart™ Therapy

Left Ventricular Systolic Unloading and Augmentation of Intracoronary Pressure and Doppler Flow During the RejuvaHeart™ Protocol.

Michaels AD, Accad M, Ports TA, Grossman W.
Circulation. 2002 Sep 3;106(10):1237-1242.

Summary: 10 patients underwent left heart catheterization significantly increasing their coronary diastolic pressure (93%), decreasing systolic pressure (15%) and their peak coronary flow velocity increased by 109% as measured by intracoronary Doppler ultrasound during external counter pulsation therapy when compared with baseline.

Endothelial Cell Function

RejuvaHeart™ Protocol Improves Endothelial Function in Patients with Symptomatic Coronary Artery Disease.

Healthy artery anatomy, artery layers detailed illustration. Erythrocytes inside the artery.

Bonetti PO, Barsness GW, Keelan PC, Schnell TI, Pumper GM, Kuvin JT, Schnall RP, Holmes DR, Higano ST, Lerman A.
Journal of the American College of Cardiology. 2003 May 21;41(10):1761-1768.

Summary: 17 (74%) of the 23 patients with refractory angina improved at least 1 symptomatic Canadian Cardiovascular Society class with a significant increase in their endothelial function as measured by reactive hyperemia-peripheral arterial tonometry (RH-PAT) index which occurred after 1 hour of ECP treatment and remained high at 1-month follow-up.

Arterial Stiffness

RejuvaHeart™ System Improves Arterial Wall Properties and Wave Reflection Characteristics in Patients With Refractory Angina.

Nichols WW, Estrada JC, Braith RW, Owens K,
Conti CR.
Journal of the American College of Cardiology. 2006 Sep 19;48(6):1209-1215. Epub 2006 Aug 25.

Summary: 34, 1-hour RejuvaHeart™  treatments in 20 stable angina patients caused a significant decline in the augmentation index and an increase in reflected wave travel time, demonstrating a reduction of arterial stiffness, resulting in a decrease in left ventricular afterload, myocardial oxygen demand and angina episodes and improved Canadian Cardiovascular Society functional class.


Effect of RejuvaHeart™ Protocol on Inflammatory Cytokines and Adhesion Molecules in Patients with Angina Pectoris and Angiographic Coronary Artery Disease.

Casey DP, Conti CR, Nichols WW, Choi CY, Khuddus MA, Braith RW.
American Journal of Cardiology. 2008 Feb 1;101(3):300-302. Epub 2007 Dec 11.

Summary: 21 patients were randomly assigned to RejuvaHeart™ protocol or sham treatment, plasma tumor necrosis factor was reduced by 29% and monocyte chemoattractant protein-1 by 19% after active treatment compared with no significant changes in the sham group. Circulating level of proinflammatory cytokines are predictors of future coronary events.

Endothelial Progenitor Cell Release

The Effect of RejuvaHeart™ Therapy on Circulating Endothelial Progenitor Cells in Patients with Angina Pectoris.

Barsheshet A, Hod H, Shechter M, Sharabani-Yosef O, Rosenthal E, Barbash IM, Matetzky S, Tal R, Bentancur AG, Sela BA, Nagler A, Leor J..
Cardiology. 2008;110(3):160-6. Epub 2007 Dec 4.

Summary: Circulating endothelial progenitor cells (EPCs) positive for CD34 measured by flow cytometry and kinase insert domain receptor (KDR) measured by the number of colony-forming units in 25 patients with angina pectoris randomized to 35 daily 1-hour RejuvaHeart™ treatment sessions (n=15) and control (n=10) were significantly increased in the RejuvaHeart™ protocol treated group and not in the control group. Patients in the RejuvaHeart™ protocol therapy group also improved their anginal score from 3.0 pre- therapy to 2.0 post therapy (p<0.001). The improvement of angina post treatment is associated with an increased number of colony-forming capacities of circulating EPCs.

Randomized Clinical Trials and Patient Registry Data in the Treatment of Angina Pectoris and Heart Failure

The Multicenter Study of RejuvaHeart™ Protocol Counterpulsation: Effect of RejuvaHeart™ treatment on Exercise-Induced Myocardial Ischemia and Anginal Episodes.

Arora RR, Chou TM, Jain D, Fleishman B, Crawford L, McKiernan T, Nesto R.
The Journal of the American College of Cardiology. 1999 Jun;33(7):1833-1840.

Summary: A multicenter (7 university hospitals), prospective, randomized, blinded, control trial of 139 angina patients with documented coronary artery disease and positive exercise treadmill tests were treated with either active counterpulsation (applied cuff pressure up to 350 mmHg), and inactive counterpulsation (<75 mmHg). Exercise duration increased in both groups, with time to ≥ 1-mm ST-segment depression increased significantly from baseline in the active group compared with the inactive group (p=0.11), as well as a significant reduction in the number of angina episodes (p<0.05). Nitroglycerin usage decreased in the active group but did not change in the inactive group; the between-group difference was not significant (p>0.7).

RejuvaHeart™ Protocol Improves Exercise Tolerance in Patients With Chronic Heart Failure.

Feldman AM, Silver MA, Francis GS, Abbottsmith CW, Fleishman BL, Soran O, de Lame PA, Varricchione T for the PEECH Investigators.
Journal of the American College of Cardiology. 2006 Sep 19;48(6):1199-1206. Epub 2006 Aug 25.

Summary: 187 subjects with mild-to-moderate symptoms of heart failure were randomized to either RejuvaHeart™ treatment with protocol-defined pharmacologic therapy (PT) or PT alone. 35% in the RejuvaHeart™ protocol therapy group and 25% in control group increased their exercise time by at least 60 sec (p=0.016) at 6 months. However, there was no between group difference in the percentage of subjects with at least 1.25 ml/kg/min increase in peak volume of oxygen uptake. New York Heart Association (NYHA) functional class improved in the active treatment group at 1-week (p<0.01), 3 months (p<0.02), and 6 months (p<0.01 post treatment). The Minnesota Living with Heart Failure score also improved significantly in the treated group at 1 week (p<0.002) and 3 months (p=0.01) after treatment, versus no significant changes in the control group.

RejuvaHeart™ Protocol Improves Exercise Duration and Peak Oxygen Consumption in Older Patients With Heart Failure: A Subgroup Analysis of the PEECH Trial.

Abbottsmith CW, Chung ES, Varricchione T, de Lame PA, Silver MA, Francis GS, Feldman AM; Prospective Evaluation of ECP in Congestive Heart Failure (PEECH) Investigators.
Congestive Heart Failure. 2006 Nov-Dec;12(6):307-311.

Summary: This paper reports the results of a pre-specified subgroup analysis of 85 elderly patients (65 years or older) enrolled in the PEECH trial. At 6-months post treatment, the percentage of subjects with >60-second increase in exercise duration was significantly higher in RejuvaHeart™ treatment patients compared with the control group (p=0.08). Moreover, in contrast to the overall PEECH study (see above), the older patient group demonstrated a significantly higher percentage of responders with >1.25 ml/kg/min increase in peak volume of oxygen consumption (p=0.017). In addition, the mean changes in exercise duration and peak oxygen consumption from baseline were significantly increased compared with the control group at 1 week, 3 months, and 6 months following completion of treatment.

Perfusion to Ischemic Region

Effects of RejuvaHeart™ Protocol on Stress Radionuclide Coronary Perfusion and Exercise Capacity in Chronic Stable Angina Pectoris.

Stys TP, Lawson WE, Hui JCK, Fleishman B, Manzo K, Strobeck JE, Tartaglia J, Ramasamy S, Suwita R, Zheng ZS, Liang H, Werner D.
The American Journal of Cardiology. 2002 Apr 1;89(7):822-824.

7-centers, 175 patients divided into two groups

Group 1
(4-centers, 97 pts)

Same Level Exercise Pre & Post ECP

Stress Nuclide Perfusion
• 83% had significant improvement
• 17% no change
• 0% worse RN
Double product no change

Group 2
(3-centers, 78 pts)

Maximal Exercise Pre & Post ECP

Stress Nuclide Perfusion
• 54% improved RN perfusion
• 42% no change
• 8% worse
Double product no change

RejuvaHeart™ Protocol in the Treatment of Chronic Refractory Angina: A Long-term Follow-up Outcome from the International External Counterpulsation Patient Registry

Loh PH, Cleland JG, Louis AA, Kennard ED, Cook JF, Caplin JL, Barsness GW, Lawson WE, Soran OZ, Michaels AD.
Clinical Cardiology. 2008 Apr 10;31(4):159-164

Experimental Studies

RejuvaHeart™ Treatment Inhibits Intimal Hyperplasia by Modifying Shear Stress Responsive Gene Expression in Hypercholesterolemic Pigs.

Zhang Y, He X, Chen X, Ma H, Liu D, Luo J, Du Z, Jin Y, Xiong Y, He J, Fang D, Wang K, Lawson WE, Hui JC, Zheng Z, Wu G.
Circulation. 2007 Jul 31;116(5):526-534. Epub 2007 Jul 9.

Summary: The coronary arteries and aortas of 35 male pigs randomly assigned to control, high-cholesterol diet and high-cholesterol diet + external counter pulsation (external counter pulsation started at week 9 to 15) were analyzed after 15 weeks. There was significant increase in peak diastolic arterial wall shear stress during RejuvaHeart™ protocol with reduction of intima-to-media area ratio by 42% compared with high-cholesterol group. ECP treated group also increased the protein expression of endothelial nitric oxide synthase suppressed the phosphorylation of extracellular signal-regulated kinases ½.


Impact of RejuvaHeart™ Treatment on Emergency Department Visits and Hospitalizations in Refractory Angina Patients with Left Ventricular Dysfunction.

RejuvaHeart™ Protocol in the Treatment of Chronic Refractory Angina: A Long-term Follow-up Outcome from the International External Counterpulsation Patient Registry

Soran O, Kennard ED, Bart BA, Kelsey SF.
Congestive Heart Failure. 2007 Jan-Feb;13(1):36-40..

Review Paper

RejuvaHeart™ Protocol and Future Directions: Step Beyond Medical Management for Patients with Angina and Heart Failure.