The Safety and Efficacy of Enhanced External Counterpulsation as a Treatment for Angina in Patients With Aortic Stenosis


  • Debra L. Braverman MD,

    Corresponding author
    1. Division of Cardiology, Einstein Institute for Heart and Vascular Health, Albert Einstein Medical Center, Philadelphia, Pennsylvania
    2. Moss Rehab, Philadelphia, Pennsylvania
    3. Jefferson Medical College, Philadelphia, Pennsylvania
    • 700 Cottman Avenue, Building B, Lower Level, Philadelphia, PA 19111
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  • Len Braitman PhD,

    1. Research and Technology Development, Albert Einstein Medical Center, Philadelphia, Pennsylvania
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  • Vincent M. Figeuredo MD

    1. Division of Cardiology, Einstein Institute for Heart and Vascular Health, Albert Einstein Medical Center, Philadelphia, Pennsylvania
    2. Jefferson Medical College, Philadelphia, Pennsylvania
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This article is corrected by:

  1. Errata: ERRATUM Volume 36, Issue 7, 433, Article first published online: 3 July 2013



Comorbid aortic stenosis (AS) has been considered a precaution when applying enhanced external counterpulsation (EECP) to individuals with angina due to concerns about treatment-related hemodynamic changes.


The aim of this study was to determine whether EECP safely reduces symptoms of myocardial ischemia and improves hemodynamics in individuals with AS.


Forty-three patients with AS (average age, 73 years; 86% male) and 43 comparison patients without AS were chosen from a database of 1327 EECP patients. Canadian Cardiovascular Society (CCS) Functional Angina Classification, diastolic augmentation ratio, and blood pressure were measured at baseline and on completion of the course of EECP.


Thirty-five of the 43 patients with AS (81%, 95% CI: 66.6% to 91.6%) and 38 of the 43 without AS (88%, 95% CI: 74.9% to 96.1%) improved in angina class (P < 0.0001). There was no statistical difference between the percentages in patients with and without AS (P = 0.54). CCS angina class outcome was not associated with AS severity (P = 0.55). The percentage of patients with diastolic augmentation ratio ≥1.0 was 16.3% in both groups at baseline and improved to 39.5% in AS patients and 37.2% in non-AS patients after EECP (both P = 0.002). The average decreases in systolic blood pressure in subjects with AS (−15 mm Hg, 95% CI: 11 to 20, P < 0.0001) and without AS (−18 mm Hg, 95% CI: 14 to 22, P < 0.0001) were similar (P = 0.31). No major adverse cardiac events were reported.


Angina patients with AS who undergo EECP had clinically important symptomatic and hemodynamic improvements comparable to their non-AS counterparts. Clin. Cardiol. 2012 doi: 10.1002/clc.22073

The authors have no funding, financial relationships, or conflicts of interest to disclose.


The overall costs of coronary heart disease approach $177.5 billion annually.1 Improved pharmacologic and invasive therapies have increased the life expectancy of such patients. However, many remain disabled by angina despite exhausting these treatments. The prevalence of refractory angina in the United States is 600 000 to 1.8 million.2 Enhanced external counterpulsation (EECP) is a noninvasive therapy for coronary artery disease (CAD) and angina. EECP has been shown to improve anginal symptoms, myocardial ischemia, left ventricular function, and quality of life.3–12

Aortic stenosis (AS) affects 2% to 4% of adults older than 65 years.13 As the population ages, the prevalence of AS is increasing.14 Atherosclerosis and calcific AS have similar predisposing risk factors (age, male gender, smoking, hypertension, and dyslipidemia)15 and share pathophysiological features.16 Fifty percent of patients with severe AS also have significant CAD.15 Patients with AS often seek medical attention because of angina. Many providers have been reluctant to use EECP in patients with severe AS, because severe AS may prevent the patient from obtaining benefit from diastolic augmentation and reduce cardiac afterload in the presence of increased venous return. The aim of this study was to determine whether EECP safely reduces symptoms of myocardial ischemia and improves hemodynamics in individuals with AS.


EECP charts from the Einstein Cardiology EECP Laboratory, Philadelphia, PA, of 1770 consecutive patients from December 2000 through June 2011 were reviewed. Four hundred forty-three patients did not complete 35 EECP treatments and were excluded from the study cohort. Of these 443 exclusions, 252 (14%) were discharged due to comorbid medical complications unrelated to EECP treatment that precluded participation in EECP, and 191 (10%) dropped out before completing the course of EECP (3.7% of whom had documented aortic stenosis). All 43 (3.2%) patients with confirmed AS documented by 2-dimensional echocardiogram who had completed at least 35 EECP treatments were included. Forty-three age- and gender-matched patients without AS from the same cohort were selected for comparison by choosing the first individual encountered in the alphabetical listing of the patient database who satisfied the matching criteria (Figure 1).

Figure 1.

Patient flow diagram. Abbreviations: AS, aortic stenosis; EECP, enhanced external counterpulsation.

Standard EECP equipment (Vasomedical Inc., Westbury, NY) was applied by standard treatment protocol. During EECP, the patient's lower extremities are wrapped in 3 pneumatic cuffs applied to the calves, lower thighs, and upper thighs. Electrocardiogram-gated sequential leg compression occurs as these cuffs are inflated from distal to proximal in early diastole to a pressure of 260 mm Hg ± 20 mm Hg, forcing blood back to the heart, augmenting diastolic pressure and assisting coronary artery filling. The cuffs are rapidly deflated at the onset of systole (Figure 2), analogous to the intra-aortic balloon pump (IABP), creating suction in the aorta, assisting ventricular ejection and reducing systolic pressure. Unlike the IABP, EECP also increases venous return, further increasing cardiac output.

Figure 2.

Sequential leg compression by enhanced external counterpulsation cuffsat 50-msec intervals during early diastole followed by simultaneous cuff deflation at the onset of systole.

During the treatment hour, the magnitude of hemodynamic change is estimated noninvasively by measuring the diastolic augmentation ratio (defined as diastolic pressure waveform divided by systolic pressure waveform), using the finger plethysmography integrated in the EECP system. Cuff inflation and deflation is adjusted based in part on this feature to maximize diastolic augmentation during treatment. The investigation conforms to the principles outlined in the Declaration of Helsinki.

The primary study outcome was the change in Canadian Cardiovascular Society (CCS) Functional Angina Classification. The secondary outcomes were the change in diastolic augmentation ratio (obtained as the average of 2 finger plethysmographic readings measured during the EECP treatment), change in CCS Functional Angina Classification according to AS severity, and change in blood pressure. All outcomes were measured at baseline prior to EECP and then compared to those measured after completion of the full course of EECP therapy.

AS severity was classified by the aortic valve (AV) area and mean gradient across the AV. Mild AS was defined as AV area >1.5 cm2 and mean gradient <25 mm Hg, moderate AS as AV area 1.0 to 1.5 cm2 and mean gradient 25 to 40 mm Hg, and severe AS as AV area <1.0 cm2 and a mean gradient >40 mm Hg.

Statistical Analysis

Paired analyses were used to assess efficacy by comparing study outcomes before and after a course of EECP. Paired t tests were performed with the accompanying 95% confidence intervals (CI) for the mean paired differences before and after the full course of EECP for the diastolic augmentation ratio, and systolic and diastolic blood pressure. The sign test was used to assess improvement in the percentages of patients with diastolic augmentation ratio ≥1 from before to after EECP. CCS before and after EECP were compared using the Wilcoxon matched-pairs signed rank test. To compare outcomes between subgroups of patients with and without AS, we used unpaired t tests for continuous outcomes and Fisher exact tests for binary outcomes. All P values were 2-sided. Statistical analyses were performed using Stata 12 (StataCorp, College Station, TX).


The average age of study patients was 76.8 years (standard deviation, 7 years; range, 59–92 years) and 74 (86%) were male. The prevalence of AS in the study group of 1327 (3.2%) was consistent with the prevalence of AS in this age range in the general population.13 The cardiac history and CAD risk factors of our cohort are reported in the Table 1. There were no significant statistical differences between the groups in regard to baseline characteristics. Most study patients had at least 1 complex, comorbid, cardiovascular condition and had undergone at least 1 revascularization procedure prior to EECP (Table 1). Medication changes were reported in 5 AS patients and 7 non-AS patients. Aortic insufficiency was present in 21 AS patients and 15 non-AS patients, none severe. Twenty-three patients had mild AS (53%), 12 had moderate AS (28%), and 8 had severe AS (19%).

Table 1. Baseline Cardiac History and Risk Factors
Cardiac History and CAD Risk FactorsWithout AS (%), N = 43With AS (%), N = 43
  1. Abbreviations: AS, aortic stenosis; CAD, coronary artery disease; N/A, not applicable.

Prior percutaneous coronary intervention18 (42)26 (61)
Prior coronary artery bypass surgery28 (65)23 (54)
Prior myocardial infarction24 (56)25 (58)
History of congestive heart failure [mean left ventricular ejection fraction %]21 (49) [47%]18 (42) [52%]
Permanent pacemaker5 (12)6 (14)
Hypertension36 (84)34 (79)
Hyperlipidemia28 (65)33 (77)
Diabetes mellitus23 (54)18 (42)
Family history of CAD35 (81)25 (58)
Smoking history35 (81)26 (61)
Syncope02 (5)
Aortic insufficiency15 (35)21 (49)
Mild ASN/A23 (53)
Moderate ASN/A12 (28)
Severe ASN/A8 (19)

Of the 43 subjects with AS, 35 (81%, 95% CI: 67% to 92%) improved in angina class (P < 0.0001) and 8 did not change; 24 improved by 1 class, 7 by 2 classes, and 4 by 3 classes. Of the 43 patients without AS, 38 (88%, 95% CI: 75% to 96%) improved in angina class (P < 0.0001) and 5 did not change; 22 improved by 1 class, 13 by 2 classes, and 3 by 3 classes. The percentages of patients with improved CCS functional angina class after EECP in patients with (81%) and without (88%) AS were similar (P = 0.54).

Improvement in CCS angina class occurred after EECP in 18 of 23 (78%) individuals with mild AS, 9 of 12 (75%) with moderate AS, and 8 of 8 (100%) with severe AS. These percentages did not differ statistically (P = 0.55).

In patients with AS, the average diastolic augmentation ratio after EECP was 0.85 compared to 0.61 before treatment, an improvement of 0.24 (95% CI: 0.16 to 0.32, P < 0.0001). In patients without AS, the average diastolic augmentation ratio after EECP was 0.92 compared to 0.67 before treatment, an improvement of 0.26 (95% CI: 0.18 to 0.33, P < 0.0001). These improvements in AS and non-AS patients were similar (P = 0.8). A diastolic augmentation ratio of at least 1.0 is the clinical goal and was present in 7 (16%) AS patients prior to EECP and improved to 17 (40%) after (P = 0.002). In non-AS patients, 7 (16%) had a diastolic augmentation ratio of at least 1.0 before EECP compared to 16 (37%) after (P = 0.01). These important clinical improvements were similar (P = 0.8).

The frequency distribution of systolic blood pressure (SBP) decreased substantially after EECP in patients with AS and without AS (Figure 3). In patients with AS, the mean SBP decreased from 134 to 119 mm Hg (−15 mm Hg, 95% CI: 11 to 20, P < 0.0001), whereas it decreased from 136 to 119 mm Hg (−18 mm Hg, 95% CI: 14 to 22, P < 0.0001) in those without AS. These average decreases in SBP did not differ statistically (P = 0.31). In AS patients, the mean diastolic blood pressure (DBP) dropped from 75 to 70 mm Hg (−5 mm Hg, 95% CI: 2 to 9, P = 0.0008) after EECP, whereas it decreased from 74 to 67 mm Hg (−7 mm Hg, 95% CI: 4 to 10, P < 0.0001) in patients without AS. These average decreases in DBP did not differ statistically (P = 0.48).

Figure 3.

Systolic blood pressure (SBP) before and after enhanced external counterpulsation (EECP). In the boxplots, the horizontal line segments in the middle of each box represent the median (50th percentile). The bottom of each box indicates the 25th percentile, whereas the top indicates the 75th percentile.

The small changes in heart rate in the AS group (average increase, 0.5 bpm) and in the non-AS group (average decrease, 1.3 bpm) were not significant (both P > 0.12). In the AS group, the average rate pressure product (RPP) decreased from 90.2 to 80.6, an average decrease of 9.6 (95% CI: 5.5 to 13.6, P < 0.0001). In patients without AS, the average RPP decreased from 95.4 to 80.2, an average decrease of 14.8 (95% CI: 10.5 to 10.1, P < 0.0001), 5.2 (95% CI: −0.6 to 11.1, P = 0.08) more in the patients without AS.

No major adverse cardiac events were reported throughout the EECP treatment period, including no myocardial infarction, unstable angina, development or progression of heart failure, persistent arrhythmias, symptom-driven revascularization, or death.


This is the first study to demonstrate the safety and efficacy of EECP in patients with both AS and angina. Our primary outcome, the CCS Functional Angina Classification, improved in 81% of patients with AS (independent of AS severity) and 88% of patients without AS, which is comparable to the general reported rate of anginal improvement from EECP in patients without AS (81%–88%).5,17–21

Surgical AV replacement is the only effective treatment for severe AS in patients with symptoms of left ventricular systolic dysfunction. However, in those who are asymptomatic or have increased operative risks, the decision to proceed with surgery is controversial.22–24 In elderly patients with AS, the etiology of symptoms may be unclear due to comorbid symptoms that may overlap with AS symptoms.25

Previously published studies26 have reported that half of AS patients with angina have CAD; the other half have increased myocardial oxygen demands in the setting of inadequate perfusion. The myocardium becomes hypertrophied to maintain cardiac output and systolic function against increasing afterload in AS.27 There is reduced coronary flow reserve and a transmural perfusion gradient leading to myocardial ischemia.28 Patients with symptomatic CAD or AS present similarly, and may seek EECP to alleviate such symptoms.

The acute hemodynamic effect of counterpulsation is augmentation of aortic diastolic pressure and mean intracoronary pressures (93% and 16%, respectively) and a decrease in left ventricular systolic pressure (15%).29 In this study, more than twice as many patients had diastolic augmentation ratio >1.0 after EECP compared to before. Counterpulsation increases the transvalvular pressure gradient, which is associated with increased stroke volume. In patients with severe AS who are hemodynamically decompensated, counterpulsation with the IABP results in substantial clinical improvement due to augmentation of the diastolic coronary filling gradient. This suggests that ischemia is the major cause of such decompensation.30,31

Vasomedical, Inc., the manufacturer of EECP therapy systems, lists clinically significant valvular disease as a precaution to providing EECP. They state that in the setting of increased venous return during EECP, clinically significant AS may prevent diastolic augmentation and afterload reduction.32 In this study, patients with AS were treated successfully without pulmonary congestion or heart failure. Although EECP will not alter the anatomy of AS, it may help with the ischemic or cardiomyopathic components contributing to the individual's symptoms and functional limitations, as our data suggest.

In this study, the diastolic augmentation ratio improved similarly after EECP in patients with (+0.24) and without AS (+0.26) (both P < 0.0001), which is comparable to the mean diastolic augmentation increase reported in the general EECP population without AS (+0.20).10 The diastolic augmentation ratios were derived from peripheral vascular wave forms that are the surrogate for central blood pressure. There is an inverse relation between left ventricular filling pressure and the diastolic augmentation ratio and coronary blood flow.33 The hemodynamic effects of EECP are maximized when the ratio of diastolic to systolic flow is 1.5 or more.34 This high diastolic augmentation ratio is not achievable in all patients due to various comorbidities, and most patients with suboptimal diastolic augmentation ratios can still achieve benefits from EECP. Clinically, the goal for diastolic augmentation ratio is ≥1.0, which 37% of our patients achieved (39% without AS, 35% with AS), whereas only 9% overall in each group had a ratio ≥1.5. Higher diastolic augmentation ratios are associated with improved outcomes, particularly with a greater reduction in CCS angina class, suggesting that a clinical benefit from EECP is partly associated with the magnitude of diastolic augmentation ratio achieved.35,36

In our study, we observed improvements in blood pressure after EECP in both AS and non-AS patients. This blood pressure response to EECP has been documented in previous studies. In 1 such analysis of 108 patients, there was a decrease in SBP at the end of each EECP treatment, at the end of a course of EECP, and at 6 weeks follow-up.37 The most pronounced drop in SBP was −30 ± 17 mm Hg in patients with baseline SBP ≥141 mm Hg, and in DBP −13 ± 9 mm Hg in those with baseline DBP ≥81 mm Hg. This suggests a physiologic response to EECP that integrates improved endothelial function and vasoreactivity.37 In a retrospective case-control study of 100 consecutive angina patients (58 normotensive and 42 hypertensive with known CAD), the average decrease in SBP after EECP in normotensive individuals was 2 ± 14 mm Hg but 25 ± 11 mm Hg in hypertensive subjects. Similarly, the average decrease in DBP was 1 ± 11 mm Hg but 7.5 ± 9 mm Hg in hypertensive subjects. The authors concluded that endothelial dysfunction is common in patients with angina and CAD, and EECP produces a larger decrease in SBP and DBP in those with hypertension than in normotensive patients.38 The significant improvements in RPP in patients both with and without AS was likely due to the decreases in SBP, as the average changes in HR were negligible.

Study limitations include a referral bias, as only patients with CAD who received EECP were enrolled. By using within-patient (paired) comparisons to assess EECP efficacy, the patients served as their own controls, which controlled for all patient characteristics (observed and unobserved) that did not change over time. This study did not control for changes in medical treatment during the course of EECP. Hemodynamic data (including pulmonary and filling pressures, and cardiac output), the extent of coronary artery disease and ischemic burden, exercise tolerance pre- and post-treatment, and follow-up echocardiogram data were not available. This study was mostly conducted and applies to patients with mild/moderate AS. The next steps would be to investigate a larger cohort of patients with severe AS and to study how AS patients without CAD respond to EECP. We examined only the short-term effects of EECP. Previous studies have demonstrated EECP benefits are sustained for up to 3 years.10,39,40 In addition, major adverse cardiac events are avoided in most EECP patients 5 years following treatment.9 The results of this study cannot be generalized to women as they were a small component of the cohort. Future studies with long-term outcomes are needed, particularly focusing on female patients, as well as a randomized controlled trial to determine the direct effects of EECP in symptomatic AS patients.


EECP safely reduced symptoms of myocardial ischemia and improved hemodynamics in individuals with CAD and aortic stenosis. More than 80% of AS patients improved in CCS Functional Angina Classification after EECP, irrespective of AS severity. That rate of improvement was similar for non-AS patients. Study patients with and without AS also experienced similar and marked improvements in diastolic augmentation ratio and blood pressure after EECP. Although EECP will not improve the anatomic restrictions of AS, it may help symptomatically if there is an ischemic or cardiomyopathic component. Based on these results, EECP should be considered a viable alternative to conventional invasive, surgical, and pharmacological treatments for angina patients with and without AS.