Enhanced External Counterpulsation (EECP)
Number: 0262
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses enhanced external counterpulsation (EECP).
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Medical Necessity
Aetna considers enhanced external counterpulsation (EECP) therapy medically necessary (unless otherwise specified) for members with chronic stable angina when criteria are met:
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As a single EECP treatment course (defined as a total of 35 treatment hoursFootnote*) for members who meet all of the following criteria:
- Disabling, chronic stable angina (defined as Canadian Cardiovascular Society [CCS] Class III or IV angina, or equivalent; see Appendix); and
- Refractory to maximum medical therapy and not readily amenable to surgical intervention such as percutaneous transluminal coronary angioplasty (PTCA) or cardiac bypass due to any of the following:
- Condition is inoperable; or
- At high-risk of operative complications or postoperative failure; or
- Coronary anatomy is not readily amenable to such procedures; and
- No present comorbid conditions or contraindications that would result in excessive risk. Examples include:
- Abdominal aortic aneurysm (greater than 5 mm) or dissection
- Acute decompensated heart failure
- Any surgical intervention within 6 weeks before EECP
- Arrhythmias that may interfere with triggering of EECP system (uncontrolled atrial fibrillation, flutter and very frequent premature ventricular contractions)
- Coagulopathy with international normalized ratio (INR) of prothrombin time greater than 2.0
- Heart rate of less than 35 or greater than 125 beats per minute
- Moderate to severe aortic regurgitation
- Pregnancy or women of childbearing age who do not have a negative pregnancy test
- Recent cardiac catheterization (1–2 weeks) or arterial femoral puncture
- Recent myocardial infarction within the last 3 months
- Severe chronic obstructive pulmonary disease
- Severe hypertension greater than 180/110 mm Hg
- Severe peripheral arterial disease (PAD)
- Severe venous disease (thrombophlebitis, prior or current deep vein thrombosis or pulmonary embolism)
- Unstable angina pectoris;
Footnote1*EECP treatment is usually administered as 35 one-hour sessions, five days a week; however, two sessions may be completed in a single day if tolerated. There is no proven benefit to extending a course of EECP beyond 35 sessions. -
As a repeat course of EECP therapy when all of the following criteria are met:
- Member continues to meet all medical necessity criteria as outlined in the single EECP treatment course requirement (above); and
- Prior EECP treatment has resulted in a sustained improvement in symptoms with:
- A significant (greater than 25%) reduction in frequency of anginal symptoms; or
- Improvement by 1 or more anginal classes; and
- Three or more months has elapsed from the prior EECP treatment;
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Hydraulic versions of these devices are considered not medically necessary.
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Experimental, Investigational, or Unproven
The following EECP indications are considered experimental, investigational, or unproven because the effectiveness for these indications has not been established (not an all-inclusive list):
- Abnormal glucose tolerance
- Aortic insufficiency
- Arrhythmia
- Atherosclerosis obliterans of the lower extremity
- Chronic cerebrovascular occlusive disease
- Erectile dysfunction
- Fatigue/malaise
- Heart failure
- Hepato-renal syndrome
- Hypertension
- Improvement of exercise endurance in individuals with chronic obstructive pulmonary disease
- Improvement of sleep quality in chronic insomnia
- Long COVID (post-acute sequelae of coronavirus disease 2019)
- Microvascular angina
- Peripheral vascular disease or phlebitis
- Prevention of renal injury in individuals with cirrhosis, heart failure, and radio-contrast exposure
- Reduction in the risk of contrast-induced nephropathy in individuals with chronic kidney disease
- Restless leg syndrome
- Retinal artery occlusion
- Rotational vertebro-basilar insufficiency
- Stroke
- Sudden deafness
- Tinnitus
- Unstable angina.
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Related Policies
Background
Enhanced External Counterpulsation (EECP) is a non‑invasive, hemodynamically active therapy designed to improve coronary perfusion and reduce left‑ventricular workload by applying sequential pneumatic compression to the lower limbs during diastole. Evidence‑based clinical literature describes EECP as a structured outpatient intervention delivered as a standard 35‑hour course, typically consisting of one‑hour sessions, five days per week for seven weeks; an equivalent accelerated schedule uses twice‑daily one‑hour sessions separated by at least 30 minutes for approximately 3.5 weeks, still totaling 35 hours. Repeat EECP courses may be administered when clinically appropriate, following the same 35‑hour protocol (Sharma et al., 2013).
Enhanced External Counterpulsation (EECP) works by using sequential pneumatic compression of the lower extremities to augment diastolic blood flow and reduce cardiac workload. During each EEECP session, large pneumatic cuffs wrapped around the calves, thighs, and buttocks inflate sequentially from distal to proximal during diastole and then rapidly deflate at the onset of systole, timed to the patient’s ECG trigger. This timing creates diastolic augmentation—a boosted backward pressure wave that increases coronary perfusion pressure—and systolic unloading, which reduces afterload and myocardial oxygen demand. The physiologic effect is similar in principle to an intra‑aortic balloon pump, but achieved externally. Over a standard 35‑hour course, this hemodynamic repetition is believed to stimulate improved coronary collateral circulation, enhance endothelial function, and reduce ischemia in patients with chronic stable angina (Mielniczuk et al., 2004).
In the short term, this method of therapy is thought to deliver more oxygen to the ischemic myocardium by increasing coronary blood flow during diastole, while at the same time reducing the demand for oxygen by diminishing the work requirements of the heart. Long-term benefit is expected to result as coronary collateral flow to ischemic regions of the myocardium is increased. A full course of EECP typically involves 5 hours of treatment per week, delivered in 1- to 2-hour sessions for 7 weeks, for a total of 35 hours of treatment (Arora et al., 1999; CMS, 2006). The pivotal randomized controlled trial of EECP, the MUST-ECP trial, employed a 35-hour protocol (Arora et al., 1999). There is no reliable evidence that clinical outcomes of EECP are improved with prolonged courses of treatment. Michaels et al. (2005) reviewed registry data to assess the frequency, efficacy, predictors, and long-term success of repeat EECP therapy in relieving angina in patients who had chronic angina and had undergone a full course of EECP. Within 2 years of the initial course of EECP, the rate of repeat EECP was 18%, which occurred at a mean interval of 378 days after initial EECP. Of those who underwent repeat EECP, 70% had a decrease of 1 or more angina classes at the end of repeat EECP, with similar decreases in nitroglycerin use. Although patients who underwent repeat EECP did benefit from the 2 courses of therapy, the symptomatic improvement was not sustained. Of the patients who had repeat EECP, 59% also had class 0 to II angina compared with 82% of those who did not undergo repeat EECP (p < 0.001). Nitroglycerin use was more common in patients who underwent repeat EECP (63%) than in those who did not (45%; p < 0.0001).
EECP is legally marketed in the U.S. as an Food and Drug Administration (FDA)‑cleared device for therapeutic use. However, FDA clearance reflects device safety and performance equivalence, not clinical guideline endorsement for specific diseases. While the FDA has granted EECP 510(k) clearance for treating a variety of conditions, including stable or unstable angina pectoris, acute myocardial infarction and cardiogenic shock, the effectiveness of EECP for conditions other than stable disabling angina (e.g., heart failure and retinal artery occlusion) has not been established in the peer-reviewed medical literature.
Clinical trials have demonstrated that the beneficial effects of EECP, including increased time until onset of ischemia and a reduction in the number and severity of anginal episodes. These effects are not only sustained between treatments, but may persist for several months to 2 years after completion of a course of therapy.
Owlia et al. (2019) highlight that the Canadian Cardiovascular Society (CCS) angina severity classification is linked to mortality, myocardial infarction, and coronary revascularization based on clinical trial and registry data. This study aimed to explore the associations between CCS class, all-cause mortality, and healthcare utilization by utilizing natural language processing to extract CCS classifications from clinical notes. In this retrospective cohort study involving U.S. veterans with stable angina from January 1, 2006, to December 31, 2013, veterans with a prior diagnosis of coronary artery disease were excluded. The primary outcomes included all-cause mortality, all-cause and cardiovascular-specific hospitalizations, coronary revascularization, and one-year healthcare costs. Out of 299,577 veterans identified, 14,216 (4.7%) had at least one CCS classification extracted. The mean age of participants was 66.6 years, with 99% being male and 81% white. Over a median follow-up of 3.4 years, all-cause mortality rates per 100 person-years were 4.58, 4.60, 6.22, and 6.83 for CCS classes I, II, III, and IV, respectively. The multivariable adjusted hazard ratios for all-cause mortality compared to class I were 1.05 (95% CI, 0.95–1.15) for class II, 1.33 (95% CI, 1.20–1.47) for class III, and 1.48 (95% CI, 1.25–1.76) for class IV. Additionally, the hazard ratio for all-cause hospitalization comparing CCS IV to CCS I was 1.20 (95% CI, 1.09–1.33), with varying ratios for other hospitalization types and procedures. The study concluded that natural language processing–extracted CCS classification was positively associated with all-cause mortality and healthcare utilization, demonstrating the prognostic importance of anginal symptom assessment and documentation.
Braunwald et al. (2000) explain that the American College of Cardiology (ACC) and American Heart Association (AHA) Task Force on Practice Guidelines was established to provide recommendations for diagnosing and treating patients with known or suspected cardiovascular disease. According to the ACC/AHA guidelines for managing unstable angina (UA), patients are generally classified as having low short-term risk of death or nonfatal myocardial infarction (MI) if they do not exhibit high- or intermediate-risk features. One such feature is the presence of new-onset CCS Class III or IV angina within the past two weeks, accompanied by a moderate to high likelihood of coronary artery disease (CAD).
Manchanda and Soran (2007) stated that numerous clinical trials in the last 2 decades have shown EECP therapy to be safe and effective for patients with refractory angina, with a clinical response rate averaging 70% to 80%, which is sustained for up to 5 years. It is not only safe in patients with co-existing heart failure, but it has also been shown to improve quality of life, exercise capacity, and left ventricular function long-term. Interestingly, EECP therapy has been studied for various potential uses other than heart disease, such as restless leg syndrome, sudden deafness, hepatorenal syndrome, and erectile dysfunction. Moreover, Arora and Shah (2007) stated that EECP has been proven to provide symptomatic benefit in angina patients, but it has not been proven to show an increase in life expectancy or a decrease in cardiovascular events. Furthermore, EECP in heart failure has been proven to be safe, but its effectiveness is still uncertain.
Alexandrov et al. (2008) determined ECP's effect on middle cerebral artery (MCA) blood flow augmentation in normal controls as a first step to support future clinical trials in acute stroke. Bilateral 2-MHz pulsed wave transcranial Doppler (TCD) probes were mounted by head frame, and baseline M1 MCA TCD measurements were obtained. External counterpulsation was then initiated using standard procedures for 30 minutes, and TCD readings were repeated at 5 and 20 minutes. Physiological correlates associated with ECP-TCD waveform morphology were identified, and measurable criteria for TCD assessment of ECP arterial mean flow velocity (MFV) augmentation were constructed. A total of 5 subjects were enrolled in the study. Pre-procedural M1 MCA TCD measurements were within normal limits. Onset of ECP produced an immediate change in TCD waveform configuration with the appearance of a second upstroke at the dicrotic notch, labeled peak diastolic augmented velocity (PDAV). Although end-diastolic velocities did not increase, both R-MCA and L-MCA PDAVs were significantly higher than baseline end-diastolic values (p < 0.05, Wilcoxon rank-sum test) at 5 and 20 minutes. Augmented MFVs (aMFVs) were also significantly higher than baseline MFV in the R-MCA and L-MCA at both 5 and 20 minutes (p < 0.05). The authors concluded that ECP induces marked changes in cerebral arterial waveforms and augmented peak diastolic and mean MCA flow velocities on TCD in 5 healthy subjects. In this regard, Han and Wong (2008) stated that randomized controlled trials with a large sample size are needed to further define the safety and effectiveness of ECP in acute stroke management.
A Cochrane systematic evidence review concluded that there is a lack of reliable and conclusive evidence that EECP can improve symptoms of angina in patients with chronic stable or refractory forms of the condition (Amin et al., 2010). The authors identified 1 trial, with 139 participants, that met criteria for inclusion in the review. They found that poor methodological quality, in terms of trial design and conduct, incompleteness in reporting of the review's primary outcome, limited follow-up for the secondary outcomes, and subsequent flawed statistical analysis compromised the reliability of the reported data. The authors explained that this trial failed to address the characteristics of interest satisfactorily, in terms of severity of angina, for the participants in this review. Participants with the most severe symptoms of angina were excluded; therefore, the results of this study represent only a subsection of the broader population with the disorder, are not generalizable, and provide inconclusive evidence for the effectiveness of EECP therapy for chronic angina pectoris.
Similarly, an assessment by the National Institute for Health Research Health Technology Assessment Programme found that although EECP is cost-effective if the observed quality of life benefits are assumed to continue throughout a patient's lifetime, there is insufficient evidence for its long-term clinical effectiveness in refractory stable angina (McKenna et al., 2009).
- EECP + traction,
- EECP, and
- traction.
All patients and 50 healthy volunteers received transcranial color Doppler examination of the vertebral artery and basilar artery in both a neutral cervical spine position and a rotational position. Within 3 days after treatment, 47 (84%) patients in EECP + traction group, 32 (61%) patients in EECP group, and 8 (15%) patients in traction group achieved successful outcomes, while at 3 months' follow-up, 45 (80%) patients in EECP + traction group, 34 (64%) in EECP group, and 3 (6%) in traction group achieved successful outcomes. With head rotation, the percentage of reduction of blood flow velocities of the vertebro-basilar artery (VBA) in patients was much greater than that of the healthy volunteers (p < 0.01). After treatment, rotational blood flow velocity reduction percentage of VBA in each treatment group was much lower than that of each group before treatment. Patients in the EECP + traction group experienced the greater decrease of rotational blood flow velocity reduction percentage of VBA than patients in the EECP group. The authors concluded that EECP and traction therapy can relieve the symptoms of rotational VBI, improve the rotational reduction of vertebro-basilar blood flow, and reduce the increased arterial impedance. Moreover, they stated that further long-term investigations are needed to confirm these findings.
Shah et al. (2010) aimed to assess the true benefits of enhanced external counterpulsation (EECP) by examining its impact on Canadian Cardiovascular Society (CCS) angina class in patients with chronic stable angina. This meta-analysis included 13 prospective studies involving 949 adult patients with stable angina who received EECP treatment. A systematic literature search was conducted for studies published from 1950 to February 2009, focusing on those in English that involved human subjects, had a prospective design, and provided sufficient data on CCS angina class. The EECP regimen consisted of 35 sessions, each lasting one hour, conducted five days a week over seven weeks. The improvement in angina class was measured as the weighted proportion of patients who improved by at least one CCS class following treatment. Heterogeneity was evaluated through subgroup analyses and the Cochran Q statistic, while publication bias was assessed using funnel plots and the Egger bias statistic. The analysis revealed that 86% of patients experienced a reduction of at least one CCS score (95% confidence interval 82-90%, Q statistic p=0.008). Although funnel plots indicated some asymmetry, the Egger bias statistic suggested no significant publication bias (p=0.97). The authors concluded that further long-term studies are needed to clarify the role of EECP therapy in managing chronic stable angina, recommending it for patients who are refractory to or unsuitable for invasive treatments and/or medical management.
In a Cochrane review, Lin et al. (2012) evaluated the safety and effectiveness of EECP for acute ischemic stroke. These investigators searched the Cochrane Stroke Group Trials Register (June 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011 Issue 2), MEDLINE (1948 to June 2011), EMBASE (1980 to June 2011), CINAHL (1982 to June 2011), AMED (Allied and Complementary Medicine) (1985 to June 2011), China Biological Medicine Database (CBM) (1978 to June 2011), Chinese National Knowledge Infrastructure (CNKI) (1979 to June 2011), Chinese Science and Technique Journals Database (VIP) (1989 to June 2011), and Wanfang Data (1984 to June 2011). They also searched ongoing trials registers, reference lists, relevant conference proceedings, and contacted authors and manufacturers of EECP devices. Randomized controlled trials (RCTs) in which EECP (started within 7 days of stroke onset) was compared with sham treatment or no treatment, or EECP plus routine treatment was compared with routine treatment alone, in patients with acute ischemic stroke, were included. Two review authors independently assessed trial quality, extracted data, checked for adverse events data, and contacted trialists for missing information. These researchers included 2 trials involving 160 patients. Numbers of deaths or dependent patients at the end of at least 3 months of follow-up were not reported in either of the included trials. The outcome measure used in the included trials was only the number of participants with improvement of neurological impairment after treatment according to the Modified Edinburgh-Scandinavian Stroke Scale (MESSS) or self-making criteria. External counterpulsation was associated with a significant increase in the number of participants whose neurological impairment improved (risk ratio (RR) 1.75, 95% confidence interval (CI): 1.37 to 2.23). Only 1 trial reported no adverse events. The authors concluded that the methodological quality of the included studies was poor, and reliable conclusions could not be drawn from the present data. They stated that high-quality and large-scale RCTs are needed.
May (2013) stated that enhanced ECP (EECP) is a non-invasive therapy offered to patients with angina pectoris who have unacceptable chest pain despite medical treatment and who have no operative options. During EECP, 3 sets of pneumatic cuffs wrapped around the lower extremities are inflated to a pressure of 260 to 300 mm Hg in diastole. This creates an augmented diastolic blood pressure and an increase in coronary blood flow. The therapy is usually given for 1 hour, 5 days a week, over 7 weeks. The author concluded that EECP is known to reduce the frequency of angina, increase the quality of life, and reduce the frequency of hospitalization.
An UpToDate review on “Possibly Effective Emerging Therapies for Heart Failure” (Colucci, 2015) states that “Trials and registries of EECP included some patients with HF, some of whom had improvements in their exercise capacity following EECP therapy. The PEECH trial directly evaluated the possible benefit of EECP in patients with mild-to-moderate HF. One hundred and eighty-seven patients were randomly assigned to standard medical therapy with seven to eight weeks of EECP or standard medical therapy alone. Patients assigned to EECP were slightly more likely to increase their total exercise time by more than 60 seconds (35% versus 25% with standard medical therapy). However, EECP did not have any effect on peak VO2. Thus, this study did not achieve positive results for its two primary endpoints. In addition, the results of this single-blind trial are subject to placebo effect. Further research will be necessary to define the impact of EECP in the treatment of HF.”
Martin et al. (2014) stated that EECP improves resistance artery function in coronary artery disease patients. However, whether EECP elicits similar effects in persons with abnormal glucose tolerance (AGT) is unknown. These researchers provided novel evidence that EECP significantly improves resistance arterial function in the forearm of persons with AGT, whereas the calf only approached significance (p ≤ 0.10). These improvements were coincident with greater glycemic control, providing further insight into the potential mechanisms of EECP-mediated alterations in glycemia. These preliminary findings need to be validated by well-designed studies.
Caceres et al. (2021) highlight that EECP is a safe, noninvasive intervention that effectively reduces angina symptoms, decreases nitrate use, enhances exercise tolerance, and improves myocardial ischemia. Their study aimed to review existing literature to demonstrate the efficacy of EECP in alleviating refractory angina and enhancing the quality of life for patients with coronary artery disease (CAD). The comprehensive analysis of numerous studies indicated that EECP consistently reduces angina pectoris, extends the time to exercise-induced ischemia, decreases reliance on nitroglycerin, increases maximum workload, and improves the quality of life for patients with symptomatic stable angina. Currently, EECP is recommended for patients with symptomatic coronary artery disease (CCS angina class III and IV) who are inoperable or at high risk for complications from surgical interventions, or who continue to experience symptoms despite percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The American Heart Association and American College of Cardiology classify EECP as a Class IIb intervention for refractory angina, alongside other nonpharmacologic treatments. A repeat course of EECP is advised for patients who have experienced a sustained improvement in symptoms after prior treatment, specifically when there is a greater than 25% reduction in anginal symptoms or an improvement of one or more anginal classes, and at least three months have passed since the last EECP treatment. Studies have shown that EECP is generally safe and well-tolerated, with leg discomfort being the most common adverse effect. Contraindications for EECP include acute heart failure, recent myocardial infarction, unstable angina, severe hypertension, and certain arrhythmias, among others. Despite its introduction in the U.S. following the MUST-EECP trial in 1999, many cardiologists remain unfamiliar with EECP due to limited exposure during training, which has hindered its integration into mainstream practice. The authors state that research indicates that EECP can lead to improvements in angina, functional class, and quality of life, while also reducing healthcare costs over time. However, access to EECP centers can be challenging for patients, as they may not be conveniently located. The authors concluded that EECP is a valuable therapy that offers significant relief from angina symptoms and enhances the quality of life for patients with stable ischemic heart disease and refractory angina. While it is not intended to replace other treatments like PCI or CABG, the growing evidence supporting its effectiveness suggests that it is a viable, cost-effective option for many patients.
Caceres et al. (2021) list the following contraindications to the use of EECP:
- Acute decompensated heart failure
- Recent myocardial infarction within the last 3 months
- Unstable angina pectoris
- Severe hypertension > 180/110 mm Hg
- Coagulopathy with international normalized ratio of prothrombin time > 2.0
- Moderate to severe aortic regurgitation
- Abdominal aortic aneurysm (>5 mm) or dissection
- Arrhythmias that may interfere with triggering of EECP system (uncontrolled atrial fibrillation, flutter and very frequent premature ventricular contractions)
- Heart rate of <35 or >125 beats per minute
- Any surgical intervention within 6 weeks before EECP
- Recent cardiac catheterization (1–2 weeks) or arterial femoral puncture
- Severe peripheral arterial disease
- Severe venous disease (thrombophlebitis, prior or current deep vein thrombosis or pulmonary embolism)
- Severe chronic obstructive pulmonary disease
- Pregnancy or women of childbearing age who do not have a negative pregnancy test.
The 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guidelines assigned a Class IIb recommendation that EECP may be considered for symptom relief in patients with chronic coronary disease (CCD) who experience refractory angina and have no other treatment options available (Virani et al., 2023).
Atherosclerosis Obliterans of the Lower Extremity
Badtieva and colleagues (2019) examined the effectiveness of EECP in the treatment and rehabilitation of patients with stages I to IIB obliterating atherosclerosis of the lower extremities (OALE). A total of 68 patients aged 50 to 78 years with stages I to IIb OALE in the presence of clinical symptomatology of arterial insufficiency were examined and treated. According to the method of treatment, patients were divided into 2 groups: 32 people received standard drug therapy (a control group), and 36 patients underwent an EECP therapy cycle during the standard therapy (a study group). The frequency of characteristic complaints, pain-free walking distance, peripheral hemodynamics, and the ankle-brachial index (ABI) were assessed. Post-treatment leg pain on walking persisted in 11 (30.6%) and 25 (78.1%) patients in the study group and the control group, respectively. There were leg cramps in 9 (25.0%) and 14 (43.8%) people and cold feet in 5 (13.9%) and 25 (78.1%) patients, respectively (p < 0.05). In the study group, the considerable increase in pain-free walking distance compared to baseline values averaged 250 ± 31.2 m (p < 0.05), while that in the control group was only 64.5 ± 25.1 m (p > 0.05). The post-treatment increase in the leg and foot rheographic indices averaged 23.9% and 23.2%, respectively, in the study group and 11.9% and 12.3%, respectively, in the control group. The increases in ABI in the anterior and posterior tibial arteries were 31.4% and 35.2%, respectively, in the study group (p < 0.05), and 16.0% and 13.0%, respectively, in the control group (p > 0.05). The authors concluded that the findings of this study suggested that the use of EECP in the combination therapy of patients with stages I to IIb OALE was safe and effective. These preliminary findings need to be validated by well-designed studies.
Chronic Cerebrovascular Occlusive Disease
Buschmann and associates (2018) noted that EECP improves cerebral perfusion velocity in acute stroke and may stimulate collateral artery growth. However, whether (non-acute) at-risk patients with high-grade carotid artery disease may benefit from EECP needs to be validated. In this study, a total of 28 patients (71 ± 6.5 years, 5 women) with asymptomatic unilateral chronic severe internal carotid artery stenosis (greater than 70%) or occlusion were randomized to receive 20 minutes of active EECP followed by sham treatment or vice versa. Cerebral blood flow velocity (CBFV) (measured bilaterally by transcranial middle cerebral artery Doppler), tissue oxygenation index (TOI) (measured over the bilateral prefrontal cortex by near-infrared spectroscopy), and cerebral hemodynamic parameters, such as relative pulse slope index (RPSI), were monitored. Ipsilateral mean CBFV (ΔVmean +3.5 ± 1.2 cm/s) and tissue oxygenation (ΔTOI +2.86 ± 0.8) increased significantly during active EECP compared to baseline, while the sham had little effect (ΔVmean +1.13 ± 1.1 cm/s; ΔTOI +1.25 ± 0.65). On contralateral sides, neither EECP nor sham control had any effect on either parameter. During EECP, early dynamic changes in ΔRPSI of the ipsilateral CBFV signal predicted improved tissue oxygenation during EECP (odds ratio [OR] 1.179, 95% CI: 1.01 to 1.51), while baseline cerebrovascular reactivity to hypercapnia failed to show an association. The authors concluded that in patients with high-grade carotid disease, ipsilateral cerebral oxygenation and blood flow velocity were increased by EECP. This is a necessary condition for the stimulation of regenerative collateral artery growth and thus a therapeutic concept for the prevention of cerebral ischemia. These researchers stated that the findings of this study provided a rationale for further investigations on the long-term effects of EECP on cerebral hemodynamics and collateral growth. They stated that future studies in chronic carotid artery occlusion should examine if repetitive EECP can lead to persistent elevation in cerebral oxygenation and whether it can improve cerebral collateral flow.
The authors stated that this study had several drawbacks. First, only a small number of participants (n = 28) were recruited. In order to fully elucidate the potential of the techniques, data are needed for a higher number of clinically stable and asymptomatic patients, with mostly ipsilateral impaired auto-regulatory reserve. Second, the majority of the study population was men; thus, it would be important to recruit a more gender-balanced cohort for future investigations. Furthermore, prospective long-term and multi-center studies are needed in order to analyze whether EECP has a sustained effect on CBFV and TOI. Finally, functional analyses following treatment with EECP are needed to evaluate any improvement in cognitive function and compensatory vascular remodeling processes.
Erectile Dysfunction
Raeissadat and colleagues (2018) reviewed the effectiveness of EECP in patients suffering from erectile dysfunction (ED). PubMed, Medline, Google Scholar, Tripdatabase, Scopus, and Cochrane library databases were searched for articles with the following search terms: enhanced external counterpulsation and erectile dysfunction. No restrictions with respect to study setting, date of publication, and language were imposed. From an initial set of 208 records, 4 studies were selected after a final review. A total of 177 patients with a mean age of 59.98 years were included in these studies, with 20 to 35 hours/week of EECP treatment; 3 studies used the International Index of Erectile Function questionnaire and 1 applied a four-item questionnaire and a peak systolic flow measurement. All of these parameters were significantly improved after the EECP treatment. The authors concluded that to the best of their knowledge, this was the first study reviewing the clinical effectiveness of EECP in patients with ED. According to the articles reviewed in this study, an improvement in erectile function following EECP treatment courses has been observed in patients with and without coronary artery disease without any significant adverse effects. Moreover, these investigators stated that since the safety and effectiveness of EECP were observed in non-controlled studies, there is a need for well-designed randomized clinical trial studies with larger sample sizes and long-term follow-up periods to evaluate this new and non-invasive therapeutic option in patients suffering from ED by excluding the confounders.
Heart Failure
Xu et al. (2023) stated that heart failure (HF) is a serious health problem worldwide, and coronary artery disease is one of the main causes. Currently, the therapeutic options for ischemic HF (IHF) are limited. In a systematic review, these investigators examined the available evidence on EECP as a non-invasive cardiac rehabilitation approach in patients with IHF and made a preliminary exploration of its mechanisms. According to available evidence, the standard course of EECP is safe in patients with IHF and can significantly improve the quality of life (QOL) of these patients. The effect of EECP on systolic function is still unclear, while EECP has a significant improvement effect on cardiac diastolic function. At the same time, this treatment can reduce the re-hospitalization rate and emergency room (ER) visit rate of patients within 6 months. In terms of mechanisms, in addition to the immediate hemodynamic effect, available evidence mostly suggested that its improvement of cardiac function may be derived from its up-regulation of shear stress to improve myocardial perfusion. The authors concluded that EECP is safe to use in patients with stable IHF, and it can improve the performance status of patients and may be beneficial to cardiac function and reduce the short-term re-hospitalization rate. Moreover, these researchers stated that there are still many limitations in the exploration of EECP use in patients with IHF. First, the lack of large-scale RCTs, existing research designs had shortcomings such as small sample size, non-blinding, high heterogeneity, which affected the reliability of results. Second, the lack of long-term follow-up observation limited the data on the safety and effectiveness of EECP in patients with IHF. Third, the evaluation indicators were relatively single, the comprehensive use of echocardiography, speckle-tracking imaging, cardiac magnetic resonance imaging (MRI), and other methods can more comprehensively and sensitively examine changes in cardiac function. Fourth, in terms of examining the mechanisms, it is currently mainly limited to its improvement in myocardial perfusion. These investigators stated that future research should examine if EECP can directly enhance myocardial cell contractility to improve cardiac function.
Improvement of Exercise Endurance in Individuals with Chronic Obstructive Pulmonary Disease
Zhao and colleagues (2020) noted that EECP is popular in China for the treatment of coronary heart diseases, but it may be an effective treatment for other populations. In a pilot study, these researchers examined the effect of EECP on exercise endurance of healthy people and chronic obstructive pulmonary disease (COPD) patients and provided intervention measures to improve their physical condition. Patients were randomly divided into the EECP and non-EECP groups. According to their maximal oxygen uptake, the volunteers were also sub-grouped into the normal, low exercise endurance, and COPD subgroups. Differences in exercise endurance were evaluated between the EECP and non-EECP groups before and after treatment. Cardiopulmonary exercise testing included anaerobic threshold oxygen uptake (AT-VO2Kg), maximum oxygen uptake (Max-VO2Kg), anaerobic threshold pulse (AT-O2puls), anaerobic threshold metabolic equivalent (AT-Mets), and maximum metabolic equivalent (Max-Mets). A total of 72 volunteers were enrolled. The EECP and non-EECP groups were similar in terms of age, sex, body mass index (BMI), blood pressure, heart rate, breathing frequency, AT-VO2Kg, Max-VO2Kg, AT-O2puls, AT-Mets, and Max-Mets (p > 0.05) before treatment. EECP significantly improved AT-VO2Kg, Max-VO2Kg, AT-O2puls, AT-Mets, and Max-Mets compared with the non-EECP group (p < 0.05). When analyzed according to sub-groups, the AT-VO2Kg, Max-VO2Kg, AT-O2puls, AT-Mets, and Max-Mets of the normal, low exercise endurance, and COPD subgroups were all significantly increased after EECP (p < 0.05). The authors concluded that EECP significantly improved the exercise endurance of normal adults, low endurance adults, and COPD patients. Moreover, these researchers stated that these findings need to be validated using a large-scale, multi-center clinical trial. The drawbacks of this trial included the small sample size (n = 13 in the EECP COPD-subgroup), and short-term follow-up. Furthermore, stratified randomization was not used.
Improvement of Sleep Quality in Chronic Insomnia
In a randomized, participant-blind, sham-controlled, pilot study, Xu et al. (2024) examined the short-term effectiveness of EECP on patients with chronic insomnia. A total of 46 subjects with chronic insomnia were randomly assigned in a 1:1 ratio to receive EECP or sham EECP intervention (a total of 35 sessions with 45 mins each). The primary outcome was Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes included sleep diary, Hospital Anxiety and Depression Scale (HADS), Short-Form Health Survey (SF-12), flow mediated dilation (FMD), serum biomarkers of melatonin, cortisol, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP). Outcomes were assessed after treatment and at 3-month follow-up. The PSQI was significantly decreased in both EECP and sham groups after 35-session intervention (13.74 to 6.96 in EECP, and 13.04 to 9.48 in sham), and EECP decreased PSQI more than sham EECP (p = 0.009). PSQI in the 2 groups kept improved at 3-month follow-up. After treatment, the total sleep time, sleep efficiency, FMD value, and SF-12 mental component of EECP group were significantly improved, and group differences were found for these outcomes. At follow-up, total sleep time, sleep efficiency, and SF-12 mental component of EECP group remained improved, and group difference for SF-12 mental component was found. Post-treatment and follow-up HADS-A significantly decreased in both groups, with no differences between the 2 groups. Post-treatment serum biomarkers showed no differences within and between groups. The authors concluded that EECP could improve sleep quality and mental QOL in patients with chronic insomnia and the therapeutic effect maintained for 3 months. These researchers stated that the main drawback of this study was the lack of objective sleep measurement. Further investigations are needed to validate the preliminary findings of this pilot study.
Long COVID
Varanasi et al. (2021) stated that a growing number of patients diagnosed with coronavirus disease 2019 (COVID-19) have been reported to have postural orthostatic tachycardia syndrome (POTS) following the acute phase. A 57-year-old woman was diagnosed with COVID-19 in December 2020. As a result of her acute illness, she was hospitalized for COVID pneumonia and respiratory failure, followed by stays at an acute care facility and a home rehabilitation center. After the acute phase, the patient was diagnosed with long-COVID-19-associated POTS, with symptoms such as fatigue, "brain fog," and dyspnea. The patient was referred to an EECP treatment center and underwent 15 one-hour sessions over 3 weeks. Upon completion of therapy, the patient reported improvements in "brain fog" and the ability to perform activities of daily living (ADL). Her Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue score was reduced by 3 points, her six-minute walk distance (6MWD) increased by 85 feet, and her Duke Activity Status Index (DASI) improved by over 15 points. EECP therapy was chosen due to the overlap in underlying pathology driving POTS and the mechanisms of action of EECP. The authors concluded that this report was the first case of using EECP for the successful management of COVID-19-associated POTS and warranted further trials.
Dayrit et al. (2021) noted that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. As patients recover from COVID-19, some continue to report persisting symptoms weeks to months after acute infection. These effects have been referred to as post-acute sequelae of SARS-CoV-2 infection (PASC). These investigators reported the case of a 38-year-old woman suffering from PASC symptoms following acute COVID-19 in October 2020. During her acute infection phase, she had a home recovery and reported her predominant symptoms as fatigue, headaches, body pain, and shortness of breath. After most of her symptoms were resolved, she continued to have periodic episodes of fatigue and headaches, along with random shortness of breath while at rest and during activities for months beyond the acute phase of the illness. She also noted the presence of "brain fog," as if lacking the same clarity that she had before her illness. These symptoms persisted for 3 months before the patient underwent EECP therapy in one-hour sessions, three times per week. This therapy was chosen based on the mechanism of action of EECP benefiting patients with ischemic cardiovascular diseases. After one week, her "brain fog" had improved, with shortness of breath improving after 1.5 weeks. The patient reported returning to pre-COVID health and fitness following about 5 weeks of EECP treatment. The authors concluded that, to their knowledge, this was the first case of using EECP for post-COVID shortness of breath, fatigue, and "brain fog." These researchers stated that further investigation is needed to validate these findings.
Joli et al. (2022) noted that fatigue is recognized as one of the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. In a systematic review, these investigators described symptoms, etiology, possible risk factors related to post-COVID-19 fatigue, and the therapeutic approaches used for the treatment of post-COVID-19 fatigue. For the systematic literature search, the databases PubMed, Web of Science, Cochrane Library, and PsycInfo were employed. All studies that met the inclusion criteria were analyzed for demographics, clinical data, and treatment. Included were studies that focused on an adult population (18 to 65 years of age); elderly patients and patients with chronic somatic diseases that could also cause fatigue were excluded. These researchers identified 2,851 studies, screened 2,193, and finally included 20 studies with moderate-to-high methodological quality, encompassing 5,629 subjects. Potential risk factors for post-COVID-19 fatigue were old age, female sex, severe clinical status in the acute phase of infection, a high number of co-morbidities, and a pre-diagnosis of depression/anxiety. Finally, a possible autoimmune etiology was suspected. Several therapeutic options have been tested, mostly in small and uncontrolled studies so far: a Chinese herbal formulation improved breathlessness and fatigue. Moreover, molecular hydrogen (H2) inhalation had beneficial health effects in terms of improved physical (6MWD) and respiratory function in patients with post-COVID-19. Patients also noticed improvement in fatigue after undergoing hyperbaric oxygen therapy (HBOT) and EECP. Finally, muscle strength and physical function were improved after undergoing an 8-week bi-weekly physical therapy (PT) course, including aerobic training, strengthening exercises, diaphragmatic breathing techniques, and mindfulness training. However, the authors stated that larger and controlled studies (e.g., examining the effect of physical and/or psychotherapy for patients with post-COVID-19 fatigue) are needed.
In a retrospective analysis of a contemporary, consecutive patient cohort, Sathyamoorthy et al. (2022) examined the use of EECP as a possible therapy for long COVID. This trial was carried out in 7 outpatient treatment centers; subjects received 15 to 35 EECP treatments. Main outcome measures included the change from baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue; Seattle Angina Questionnaire (SAQ); Duke Activity Status Index (DASI); 6MWD; Canadian Cardiovascular Society (CCS) Angina Grade; Rose Dyspnea Scale (RDS); and Patient Health Questionnaire (PHQ-9). Compared to baseline, the PROMIS Fatigue, SAQ, DASI, and 6MWD improved by 4.63 ± 3.42 (p < 0.001), 21.44 ± 16.54 (p < 0.001), 18.08 ± 13.82 (p < 0.001), and 200.00 ± 180.14 (p = 0.002), respectively. CCS and RDS improved in 63% and 44% of patients, respectively. All patients unable to work before EECP were able to return post-therapy. The authors concluded that EECP significantly improved validated fatigue and cardiovascular-related markers in patients with long COVID. These researchers stated that these findings suggested that EECP may be beneficial for the management of long COVID symptoms; these promising findings are hypothesis-generating and should be further examined in a broader clinical investigation.
An UpToDate review on “COVID-19: Evaluation and Management of Adults with Persistent Symptoms Following Acute Illness ("Long COVID")” (Mikkelsen and Abramoff, 2022) did not mention EECP as a management/therapeutic option.
Furthermore, the 2022 American College of Cardiology (ACC)’s Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults (Gluckman et al., 2022) did not mention the use of EECP as a management option.
Huang et al. (2025) noted that some of the millions of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have developed new sequelae after recovering from the initial disease, termed post-acute sequelae of coronavirus disease 2019 (PASC). One symptom is anxiety, which is likely due to three etiologies: brain structural changes, neuroendocrine disruption, and neurotransmitter alterations. These investigators provided an overview of the available evidence on the pathophysiological pathways linking COVID-19 to anxiety, as well as the possible mechanisms of action in which an increasingly scrutinized treatment method, EECP, is able to alleviate anxiety. SARS-CoV-2 triggers increased inflammatory cytokine production, as well as oxidative stress; these processes contribute to the aforementioned three etiologies. The potential treatment approach of EECP, entailing sequenced inflation and deflation of specifically placed airbags, has become of increasing interest, as it has been found to alleviate PASC-associated anxiety by improving patient cardiovascular function. These functional improvements were achieved by EECP stimulating anti-inflammatory and pro-angiogenic processes, as well as improving endothelial cell function and coronary blood flow, partially by counteracting the negative effects of SARS-CoV-2 infection on the renin-angiotensin-aldosterone system. Thus, EECP could promote both psychosomatic and cardiac rehabilitation. Moreover, these researchers stated that further investigations are still needed to ascertain its benefits and mechanism of action.
Microvascular Angina
According to the American Heart Association (AHA), microvascular angina is a type of chest pain that typically lasts more than 15-20 minutes and can be a symptom of coronary microvascular disease (MVD), which affects the smallest blood vessels in the heart. This form of angina may differ from typical angina associated with heart disease, as it often presents as a dull chest pain that is more severe and prolonged. It may also be accompanied by shortness of breath and is frequently first noticed during daily activities or periods of mental stress. Other symptoms can include sweating, nausea, dizziness, stomach pain, and unusual fatigue. Treatment for MVD may involve medications that improve blood vessel function and reduce the risk of complications, such as ACE inhibitors, anticoagulants, aspirin, beta blockers, calcium channel blockers, statins, diuretics, and nitrates. Patients with MVD should adhere to their healthcare provider's recommendations regarding symptom management and when to seek medical attention. The AHA does not provide a recommendation for EECP as a treatment method (AHA, 2025).
Wang and colleagues (2023) investigated the outcomes of EECP in patients with coronary microvascular disease (CMD). Their prospective, randomized control trial involved 41 patients in the EECP cohort and 42 in the control group. Coronary flow reserve (CFR) was measured using transthoracic Doppler echocardiography before and after a 4-week EECP program, while serum levels of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) were analyzed via ELISA. Quality of life (QoL) was assessed using the Seattle Angina Questionnaire (SAQ) and the Canadian Cardiovascular Society (CCS) angina class. Results showed a significant improvement in CFR in the EECP group compared to controls (p<0.05), along with a marked decrease in ET-1 and a notable increase in eNOS levels. Additionally, EECP improved SAQ scores and reduced the CCS angina class. The authors concluded that EECP may enhance CFR and QoL in CMD patients, but acknowledged limitations, including the single-center design, the small sample size that hindered the ability to determine clinical outcome differences between groups, the lack of flow-mediated dilation to assess endothelial function, and the complexity of EECP-related mechanisms, suggesting that further research is needed to confirm the benefits of EECP in this patient population.
Smilowitz et al. (2023) highlight that angina with nonobstructive coronary arteries (ANOCA) is a prevalent yet often overlooked clinical condition that poses challenges for healthcare providers, as it does not fit within the traditional frameworks for managing obstructive atherosclerotic disease. This necessitates the development of new diagnostic systems and techniques, and there is limited data on treatment options and outcomes. However, advancements in the field have brought ANOCA to global attention, leading to significant progress in understanding how to effectively manage these patients. In 2021, the Microvascular Network was established to create a North American community of physicians and advanced practice providers, both academic and community-based, aimed at developing a common language and standardized strategies for diagnosing and treating patients with microvascular dysfunction and related coronary disorders, such as endothelial dysfunction, vasospasm, and myocardial bridging, across various clinical contexts, including chronic angina, acute coronary syndromes, and cardiomyopathies. While considering international guidelines and consensus documents, the focus was on tailoring approaches to the specific expertise, patient populations, clinical environments, and available medical resources in North America, resulting in a two-part review on the comprehensive management of ANOCA. Part 2 discusses the essential components for establishing a comprehensive coronary function testing (CFT) center, the evidence supporting current treatment options, and clinical variables that can facilitate standardized care and enhance research initiatives. The authors report that EECP, a noninvasive technique that increases diastolic augmentation and reduces afterload, has shown sustained improvements in angina and coronary flow reserve (CFR) in nonrandomized studies involving ANOCA patients. EECP is approved for treating Canadian Cardiovascular Society Angina Class 3 or 4 angina despite medical therapy; however, its role in the treatment of ANOCA warrants further investigation.
Ashokprabhu et al. (2024) reported that the primary cause of angina with no obstructive coronary artery disease (ANOCA) in most patients is endothelial and nonendothelial coronary microvascular dysfunction (CMD) and coronary vasospasm, which are diagnosed through coronary functional testing. ANOCA is linked to a higher risk of major adverse cardiac events, reduced quality of life, and increased healthcare costs. Currently, antianginal treatments for ANOCA are limited to β-blockers, calcium channel blockers, nitrates, and ranolazine. While enhanced external counterpulsation (EECP) is approved for treating refractory angina due to obstructive coronary artery disease, its effectiveness in patients with ANOCA remains largely unproven, relying on small studies. In a retrospective analysis, the authors evaluated the efficacy of EECP in 101 patients with ANOCA (defined as ≤50% stenosis in any major epicardial vessels) and refractory angina by measuring changes in Canadian Cardiovascular Society (CCS) angina class, 6-minute walk test, Duke Activity Status Index (DASI), Seattle Angina Questionnaire 7 (SAQ7), and weekly anginal episodes before and after EECP treatment. The cohort had a mean age of 60.6 years, with 62.4% being women. Significant improvements were observed post-EECP in CCS angina class (from 3.4 to 2.4, p <0.001), 6-minute walk test (from 1200 to 1358 meters, p <0.001), DASI (from 15.2 to 31.5, p <0.001), SAQ7 (from 36.2 to 31.5, p <0.001), and weekly anginal episodes (from 5.3 to 2.4, p <0.001). Notably, 71 patients (70.3%) experienced an improvement of at least one CCS angina class, with 33 (32.7%) improving by two or more classes. The authors concluded that EECP therapy reduces CCS angina class and enhances exercise tolerance in ANOCA patients, suggesting it should be included in optimal medical therapy. However, they acknowledged several limitations, including the lack of a randomized controlled trial design, which leaves the effects of a sham placebo group uncertain, and that endpoints were measured only at the last EECP visit, potentially missing longer-term benefits. Additionally, the retrospective nature of the analysis meant that not all validated questionnaire data were available for every patient, and the limitations of data extraction from electronic health records should be considered. Despite these limitations, the authors state that their study represents the largest investigation of EECP therapy in ANOCA patients to date.
Peripheral Vascular Disease
In a randomized study, Zhang et al. (2024) examined the effects of EECP and individual shear rate therapy (ISRT) on peripheral artery function in patients with lower extremity atherosclerotic disease (LEAD). These researchers assigned 45 LEAD patients to receive 35 sessions of 45 minutes of EECP (n = 15), ISRT (n = 15), or sham-control (n = 15). Flow-mediated dilation in the brachial artery (brachial-FMD), six-minute walk distance (6MWD), blood flow in the popliteal, posterior tibial, anterior tibial, and dorsalis pedis arteries, as well as plasma levels were measured before and after the 7 weeks of treatment. The 36-item Short Form Health Survey (SF-36) was analyzed before, after 7 weeks, and at 3-month follow-ups.
EECP treatment significantly improved brachial-FMD and quality of life (QOL), increased walking distance, and enhanced blood flow and the diameters of the popliteal artery and posterior tibial artery (all p < 0.01). In contrast, ISRT markedly increased blood flow in the anterior tibial artery (p < 0.05). Both EECP and ISRT decreased the levels of endothelin-1 and asymmetrical dimethylarginine in patients with LEAD (both p < 0.01). Furthermore, soluble vascular cell adhesion molecule-1 (sVCAM-1) was significantly reduced following EECP intervention (p = 0.004). The authors concluded that the findings of this study showed that EECP and ISRT exhibited beneficial effects on walking distance, QOL, flow-mediated dilation, endothelial-derived vasoactive agents, and inflammatory and oxidative stress in LEAD patients. Moreover, these investigators stated that further investigations are needed.
The authors noted several drawbacks of this study. First, although the trial showed important findings from different perspectives, the overall sample size was relatively small (n = 15 in the EECP group). Second, conducting a subgroup analysis of the specific location of stenosis in patients was challenging due to the limited sample size. Increasing the sample size in future studies could provide a stronger experimental basis for clinical randomized controlled trials. Third, the inclusion criteria lacked specificity, as Rutherford’s grading was not included in this study. These investigators anticipated that further research would provide more comprehensive analyses. Fourth, this trial did not examine the molecular mechanisms underlying the clinical benefits.
Prevention of Renal Injury in Patients with Cirrhosis, Heart Failure, and Radio-Contrast Exposure
Thongsricome et al. (2023) stated that EECP is provided by a non-invasive device that positively affects cardiovascular function via mechanisms called diastolic augmentation and systolic unloading. The renal aspects of EECP therapy have not been extensively investigated. In a systematic review, these investigators examined the effect of EECP on renal function and its application in patients with kidney disease. Medline, Embase, SCOPUS, and Cochrane CENTRAL databases were searched for all studies involving EECP treatments. The title and abstract of all searched literature were screened, and those focusing on renal outcomes or conducted in kidney disease patients were selected. A total of 8 studies were included in the qualitative analysis.
EECP was found to increase stroke volume (SV), mean arterial pressure (MAP), renal artery blood flow, renal plasma flow, glomerular filtration rate (GFR), plasma atrial natriuretic peptide, urine volume, and urinary sodium chloride excretion, while decreasing the plasma concentration of renin and endothelin-1 in healthy subjects. A single session of EECP after radio-contrast exposure could provide enhanced contrast clearance, reducing contrast-induced renal injury in patients, irrespective of previous renal function. Additionally, 35 one-hour sessions of EECP treatment were illustrated to increase long-term estimated GFR in patients with chronic angina and heart failure. However, in cirrhotic patients, EECP failed to improve GFR and renal vascular resistance. The EECP device could maintain blood pressure, decrease angina symptoms, and increase cardiac perfusion in hemodialysis patients. The authors concluded that EECP treatment potentially increased renal perfusion and prevented renal injury in several conditions; it possibly provided beneficial effects on hemodynamics and cardiac function in hemodialysis patients. However, close surveillance for possible additional adverse effects following the application of EECP in this group of patients is needed.
The authors stated that this was the first study to comprehensively examine the application of EECP in patients with renal diseases. They noted that the main drawback of this review was that only a few studies were included in the analysis, which impeded the performance of a meta-analysis. Moreover, the varied quality assessment of the included studies necessitated more mechanistic and clinical studies with good study design, larger sample sizes, more diverse patient subgroups, adequate follow-up time, and hard endpoints before a final consensus on this topic could be drawn.
Reduction in the Risk of Contrast-Induced Nephropathy in Patients with Chronic Kidney Disease
In a prospective study, Zen et al. (2024) examined the effectiveness of EECP in the prevention of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD). This trial included 280 patients with an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m² who underwent percutaneous coronary artery procedures. Subjects were divided into 2 groups: the control group (n = 100) and the EECP group (n = 180). All participants received extra-cellular fluid (ECF) volume expansion therapy with 0.9% normal saline, and subjects in the EECP group were also treated with EECP. The renal function indexes of the 2 groups were determined 48 to 72 hours after coronary artery procedures. In the EECP group, the BUN and serum creatinine (Scr) after coronary artery procedures were significantly lower than those before coronary artery procedures (BUN: 8.4 ± 3.5 versus 6.6 ± 2.7 mmol/L, p < 0.001; Scr: 151.9 ± 44.7 versus 144.5 ± 48.3 μmol/L, p < 0.001), while the eGFR was significantly increased (43.6 ± 11.4 versus 47.1 ± 13.9 ml/min/1.73 m², p < 0.001). The degree of Scr elevation was lower in the EECP group than in the control group (12.4 ± 15.0 versus 20.9 ± 24.8 μmol/L, p = 0.026). Furthermore, the EECP group had a lower incidence of post-procedures Scr elevation than the control group (36.5% versus 48.0%, p = 0.042), a higher incidence of post-procedures eGFR elevation (62.2% versus 48.0%, p = 0.021), and a lower risk of CIN (1.1% versus 6.0%, p = 0.019). The authors concluded that EECP therapy has a protective effect on renal function and could reduce the risk of CIN in patients with CKD. Moreover, these researchers stated that further investigations are needed to confirm these findings.
The authors stated that this study had several drawbacks. First, due to the fact that the patients were scheduled to be discharged 2 to 3 days after coronary artery procedures, and considering factors such as distance from their place of residence, transportation, cost, and patient willingness, renal function data from a few weeks later were unavailable. From previous studies, EECP has been shown to enhance renal blood flow perfusion, promote renal excretion, and alleviate inflammatory response. Theoretically, it has a protective effect on renal function. If the duration of EECP treatment is extended, such as 6 times a week, 1 hour per session, for 6 weeks, for a total of 36 hours, the authors have not seen any relevant literature reports on the impact on renal function. Second, the amount of contrast agent administered was not accurately recorded but was indirectly estimated using the duration of coronary artery procedures. Furthermore, no urine data was collected, such as urinary micro-albumin and N-acetyl-β-D-glucosaminidase (NAG), and urine beta 2 microglobulin are indicators used to evaluate early renal function damage. Third, due to the limitation of sample size, this study did not perform multi-variate regression analysis to mitigate confounding factors. Fourth, the majority of patients did not undergo hyper-sensitive C-reactive protein (Hs-CRP) testing upon admission; thus, pre-operative Hs-CRP data could not be provided. From previous studies, Hs-CRP levels have been found to be associated with adverse ischemic events following PCI, with a higher risk of all-cause mortality and cardiac death associated with high Hs-CRP levels. Fifth, the protective effect of EECP on the kidney may have been mediated via improved cardiac function rather than via direct effects on the kidney, which was not examined in this trial. Considering that the basic principle of EECP reducing CIN is still unclear, and the existence of many confounding factors, such as hydration volumes and the number of patients with low ejection fraction, the next research directions include expanding the sample size to conduct RCTs and examining the effects of EECP on renal hemodynamics from a physiological perspective.
Appendix
Canadian Cardiovascular Society (CCS) Classification System for Angina Pectoris
- Class I
New York Heart Association (NYHA) Functional Classification of Cardiac Disability
Class I
Patients with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.
Class II
Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.
Class III
Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain.
Class IV
Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
Source: Adapted from Goldman et al (1981).
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