Cardiac Rehabilitation: Outpatient
Number: 0021
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses outpatient cardiac rehabilitation.
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Medical Necessity
Aetna considers outpatient (Phase II) cardiac rehabilitation medically necessary when the eligibility and program description are met as described below.
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Eligibility
Aetna considers a medically supervised outpatient Phase II cardiac rehabilitation program medically necessary for selected members when it is individually prescribed by a physician within a 12-month window after any of the following documented diagnoses:
- Acute myocardial infarction within the preceding 12 months; or
- Any major open heart surgery, including the following:
- coronary artery bypass grafting (CABG)
- great vessel surgery
- heart transplantation or heart-lung transplantation
- major pulmonary surgery
- open MAZE arrhythmia surgery
- placement of a ventricular assist device
- removal of atrial myxoma
- surgical septal myectomy via thoracotomy
- thoracic aortic aneurysm repair
- transcatheter valve replacement or repair; or
- Chronic stable angina pectoris unresponsive to medical therapy which prevents the member from functioning optimally to meet domestic or occupational needs (particularly with modifiable coronary risk factors or poor exercise tolerance); or
- Percutaneous coronary intervention (i.e., percutaneous transluminal coronary angioplasty (PTCA), atherectomy, stenting); or
- Sustained ventricular tachycardia or fibrillation, or survivors of sudden cardiac death; or
- Stable congestive heart failure (CHF) with left ventricular ejection fraction (LVEF) of 35% or less and New York Heart Association (NYHA) class II to IV symptoms despite being on optimal heart failure therapy for at least 6 weeks; stable CHF is defined as CHF in persons who have not had recent (less than or equal to 6 weeks) or planned (less than or equal to 6 months) major cardiovascular hospitalizations or procedures.
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Program Description
- Physician-prescribed exercise each day cardiac rehabilitation items and services are furnished; and
- Provides up to a maximum of two 1-hour sessions per day for up to 36 sessions over a period of 36 weeks of medically supervised exercise with or without continuous electrocardiogram (ECG) monitoring (frequency generally consists of 2 to 3 sessions per week for 12 to 18 weeks); and
- Program is under the direct supervision of a physician or other qualified health care professional (e.g., nurse practitioner [NP], physician's assistant [PA]) Note: physician, NP or PA do not have to be present in the room during the session; however, must be immediately available and accessible for medical consultations and emergencies at all times while services are being furnished under the program; and
- Facility is located in a physician's office, or outpatient hospital setting, and has the necessary cardio-pulmonary, emergency, diagnostic, and therapeutic life-saving equipment immediately available (e.g., cardiopulmonary resuscitation equipment, defibrillator); and
- An individual outpatient exercise program has been created that can be self-monitored and maintained; and
- There has been a psychosocial assessment; and
- Cardiac risk factor modification, including education, counseling and behavioral intervention is tailored to individual needs; and
- Entails an outcomes assessment (e.g., objective clinical measures of exercise performance).
Aetna considers additional cardiac rehabilitation services medically necessary when the eligible member has an additional qualifying event for any of the following conditions:
- Another cardiovascular surgery or percutaneous coronary intervention; or
- Another documented myocardial infarction or extension of initial infarction; or
- New clinically significant coronary lesions documented by cardiac catheterization.
Note: Up to an additional 36 sessions is considered medically necessary for continuation (not to exceed a total of 72 sessions).
Aetna considers cardiac rehabilitation not medically necessary for individuals following pericardiectomy for calcified constrictive pericarditits.
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Experimental, Investigational, or Unproven
- Cardiac rehabilitation programs are not recommended and are considered experimental, investigational, or unproven for individuals with coronary artery disease (CAD) who have the following conditions:
- Acute pericarditis or myocarditis; or
- Acute systemic illness or fever; or
- Clinical signs of decompensated aortic stenosis (e.g., angina pectoris and dyspnea on exertion, or syncope); or
- Forced expiratory volume less than 1 liter; or
- New-onset atrial fibrillation; or
- Progressive worsening of exercise tolerance or dyspnea at rest or on exertion over the previous 3 to 5 days; or
- Recent embolism or thrombophlebitis; or
- Third-degree heart block without pacemaker; or
- Unstable angina.
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Aetna considers cardiac rehabilitation experimental, investigational, or unproven for all other indications including the following (not an all-inclusive list) because of insufficient evidence in the peer-reviewed literature:
- Atrial fibrillation (other than following the Maze procedure)
- Following balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension
- Following repair of sinus venosus atrial septal defect
- Following thoracic aortic repair
- Individuals who are too debilitated to exercise
- Individuals who have hypertrophic cardiomyopathy
- Individuals who have undergone atrial fibrillation ablation
- Individuals who have undergone closure of patent foramen ovale
- Individuals who have undergone placement of an implantable automated cardioverter-defibrillator
- Individuals with a history of high degree atrioventricular block following implantation of a permanent pacemaker
- Individuals with Takotsubo (stress) cardiomyopathy
- Individuals with lymphoma undergoing autologous hematopoietic stem cell transplantation
- Postural tachycardia syndrome (POTS)
- Prevention of chemotherapy-induced cardiotoxicity and/or improvement of fitness in individuals with subclinical markers of cardiotoxicity while receiving chemotherapy
- Secondary prevention after stroke
- Secondary prevention after transient ischemic attack
- Uncompensated heart failure
- Uncontrolled arrhythmias.
- Cardiac rehabilitation programs are not recommended and are considered experimental, investigational, or unproven for individuals with coronary artery disease (CAD) who have the following conditions:
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Policy Limitations and Exclusions
Note: Phase III and Phase IV cardiac rehabilitation programs are not covered under standard Aetna benefit plans as these programs do not require direct supervision by a physician or advanced practitioner (NP or PA), or continuous ECG monitoring. These programs are considered educational and training in nature. Education and training programs are generally not covered under most Aetna benefit plans. Please check benefit plan descriptions.
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Related Policies
Background
Patients who have cardiovascular events are often functional in society and employed prior to a cardiac event, and frequently require only re-entry into their former life pattern. Cardiac rehabilitation (CR) serves this purpose by providing a supervised program in the outpatient setting that involves medical evaluation, a physical exercise program with electrocardiogram (ECG) monitored and non-ECG monitored sessions, cardiac risk factor modification, education, and counseling.
Cardiac rehabilitation is designed to help individuals with conditions such as heart or vascular disease return to a healthier and more productive life. This includes individuals who have had heart attacks, open heart surgery, stable angina, vascular disease or other cardiac related health problems.
Traditionally, cardiac rehabilitation programs have been classified into 4 phases, phase I to IV, representing a progression from the hospital (phase I) to a medically supervised outpatient program (phases II) to maintenance programs that are structured for community or home-based settings (phase III or IV). Phase I cardiac rehabilitation begins in the hospital (inpatient) after experiencing a heart attack or other major heart event. During this phase, individuals receive education and nutritional counseling to prepare them for discharge. Phase II outpatient cardiac rehabilitation begins after leaving the hospital. As described by the U.S. Public Health Service, it is a comprehensive, long-term program including medical evaluation, prescribed exercise, cardiac risk factor modification, education and counseling. Phase II refers to medically supervised programs that typically begin one to three weeks after discharge and provide appropriate ECG monitoring. Phase III and phase IV cardiac rehabilitation programs encourage exercise and healthy lifestyle performed at an outpatient medical facility, home or in a fitness center with the goal of continuing the risk factor modification and exercise program learned in phase II. Phase III and IV do not require direct physician supervision or continuous ECG monitoring. These programs encourage a commitment to regular exercise and healthy habits for risk factor modification to establish lifelong cardiovascular fitness. Some programs combine phases III and IV (CMS, 2006).
Cardiac rehabilitation phase II sessions can take place in an outpatient hospital setting or a physician's office (CGS, 2018). Per the Centers for Medicare & Medicaid Services (CMS, 2010) and the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR, 2019), cardiac rehabilitation sessions require direct physician supervision. Although the physician does not have to be present in the room during the CR sessions, all CR settings must have a physician immediately available and accessible for medical consultations and emergencies at all times when items and services are being furnished under the program. This provision is satisfied if the physician meets the requirements for supervision for physician office services, at section 410.26; and for hospital outpatient services at section 410.27. For pulmonary rehabilitation, cardiac rehabilitation, and intensive cardiac rehabilitation services, direct supervision must be furnished by a doctor of medicine or osteopathy, as specified in §§410.47 and 410.49, respectively (CGS, 2018). AACVPR website (2018) also state that for cardiac rehabilitation sessions "the physician does not need to be in the rehab suite but must be immediately available and interruptible".
The AACVPR recommends "adjusting levels or intensities of ECG monitoring of patients during the outpatient training phase of CR based on clinical need and patient safety. Procedures include graduated processes with an initial intensive phase of continuous ECG monitoring followed by intermittent monitoring over the course of the program, or basing the level of monitoring on the patient’s risk of cardiac events during exercise; low risk patients would be monitored less frequently than high risk patients". Furthermore, "research indicates that “modified” CR programs that limit ECG monitoring are both cost-effective and safe, while potentially improving patient adherence (Carlson, 2000). Current Medicare regulations do not mandate that CR sessions be ECG-monitored. Per American Medical Association definitions of CR CPT codes, sessions may be with ECG-monitoring (93798) or without ECGmonitoring (93797) (CPT Manual). Both procedure codes are reimbursed by Medicare at the same rate in a hospital outpatient setting" (AACVPR, 2024).
Due to changes in hospital and health care practices, and the need to accommodate patients at various stages of disease risk, some have argued that the need for phase designation becomes inappropriate, and that cardiac rehabilitation programs can be more appropriately distinguished as inpatient, outpatient or community/home-based programs. Participation within these programs is determined by appropriate risk stratification in order to maximize health care resources and patient benefit. Irrespective of the program, there should be regular communication, in the form of progress reports, between the program staff and the patient’s attending physician (Ignaszewski and Lear, 1998).
Entry into such programs is based on the demonstrated limitation of functional capacity on exercise stress testing, and the expectation that medically supervised exercise training will improve functional capacity to a clinically significant degree. The exercise test in cardiac rehabilitation is a vital component of the overall rehabilitative process as it provides continuous follow-up in a noninvasive manner and adds information to the overall physical evaluation. In general, testing is performed before entering the cardiac rehabilitation exercise program, and sequentially during the program to provide information on the changes in cardiac status, prognosis, functional capacity, and evidence of training effect. The central component of cardiac rehabilitation is a prescribed regimen of physical exercises intended to improve functional work capacity and to increase the patient's confidence and well-being. Depending on the degree of debilitation, cardiac patients may or may not require a full or supervised rehabilitation program.
The scientific literature documents that some of the benefits of participation in a cardiac rehabilitation program include decreased symptoms of angina pectoris, dyspnea, and fatigue, and improvement in exercise tolerance, blood lipid levels, and psychosocial well-being, as well as a reduction in weight, cigarette smoking and stress. The efficacy of modification of risk factors in reducing the progression of coronary artery disease and future morbidity and mortality has been established. Meta-analysis of data from random controlled studies indicates a 20 % to 25 % reduction in mortality in patients participating in cardiac rehabilitation following myocardial infarction as compared to controls.
The typical model for delivering outpatient cardiac rehabilitation in the United States is for patients to attend sessions 2 to 3 times per week for up to 12 to 18 weeks (36 total sessions) (CMS, 2006). A session typically lasts for approximately 1 hour and includes aerobic and/or resistance exercises with continuous electrocardiographic monitoring. There are alternative approaches to this typical model. Patients can be classified as low-, moderate- or high-risk for participating in exercise based on a combination of clinical and functional data. The number of recommended supervised exercise sessions varies by risk level: low-risk patients receive 6 to 18 exercise sessions over 30 days or less from the date of the cardiac event/procedure; moderate-risk 12 to 24 sessions over 60 days; and high-risk 18 to 36 sessions over 90 days (Hamm, 2008; AACVPR, 2004).
There is limited evidence on the appropriate duration of cardiac rehabilitation. Hammill et al (2010) stated that for patients with coronary heart disease, exercise-based cardiac rehabilitation improves survival rate and has beneficial effects on risk factors for coronary artery disease. However, the relationship between the number of sessions attended and long-term outcomes is unknown. In a national 5 % sample of Medicare beneficiaries, these investigators identified 30,161 elderly patients who attended at least 1 cardiac rehabilitation session between January 1, 2000, and December 31, 2005. They used a Cox proportional hazards model to estimate the relationship between the number of sessions attended and death and myocardial infarction (MI) at 4 years. The cumulative number of sessions was a time-dependent co-variate. After adjustment for demographical characteristics, co-morbid conditions, and subsequent hospitalization, patients who attended 36 sessions had a 14 % lower risk of death (hazard ratio [HR], 0.86; 95 % confidence interval [CI]: 0.77 to 0.97) and a 12 % lower risk of MI (HR, 0.88; 95 % CI: 0.83 to 0.93) than those who attended 24 sessions; a 22 % lower risk of death (HR, 0.78; 95 % CI: 0.71 to 0.87) and a 23 % lower risk of MI (HR, 0.77; 95 % CI: 0.69 to 0.87) than those who attended 12 sessions; and a 47 % lower risk of death (HR, 0.53; 95 % CI: 0.48 to 0.59) and a 31 % lower risk of MI (HR, 0.69; 95 % CI: 0.58 to 0.81) than those who attended 1 session. The authors concluded that among Medicare beneficiaries, a strong dose-response relationship existed between the number of cardiac rehabilitation sessions and long-term outcomes. Attending all 36 sessions reimbursed by Medicare was associated with lower risks of death and MI at 4 years compared with attending fewer sessions.
Pack et al (2013) noted that outpatient CR decreases mortality rates but is under-utilized. Current median time from hospital discharge to enrollment is 35 days. These researchers hypothesized that an appointment within 10 days would improve attendance at CR orientation. At hospital discharge, 148 patients with a non-surgical qualifying diagnosis for CR were randomized to receive a CR orientation appointment either within 10 days (early) or at 35 days (standard). The primary end-point was attendance at CR orientation. Secondary outcome measures were attendance at greater than or equal to 1 exercise session, the total number of exercise sessions attended, completion of CR, and change in exercise training work-load while in CR. Average age was 60 ± 12 years; 56 % of participants were male and 49 % were black, with balanced baseline characteristics between groups. Median time (95 % CI) to orientation was 8.5 (7 to 13) versus 42 (35 to NA [not applicable]) days for the early and standard appointment groups, respectively (p < 0.001). Attendance rates at the orientation session were 77 % (57/74) versus 59% (44/74) in the early and standard appointment groups, respectively, which demonstrated a significant 18 % absolute and 56 % relative improvement (relative risk, 1.56; 95 % CI: 1.03 to 2.37; p = 0.022). The number needed to treat was 5.7. There was no difference (p > 0.05) in any of the secondary outcome measures, but statistical power for these end points was low. Safety analysis demonstrated no difference between groups in CR-related adverse events. The authors concluded that early appointments for CR significantly improved attendance at orientation. This simple technique could potentially increase initial CR participation nationwide.
In a retrospective cohort study, Beauchamp et al (2013) examined if attendance at CR independently predicts all-cause mortality over 14 years and whether there is a dose-response relationship between the proportion of CR sessions attended and long-term mortality. The sample comprised 544 men and women eligible for CR following MI, coronary artery bypass surgery or percutaneous interventions. Participants were tracked 4 months after hospital discharge to ascertain CR attendance status. Main outcome measure was all-cause mortality at 14 years ascertained through linkage to the Australian National Death Index. In total, 281 (52 %) men and women attended at least 1 CR session. There were few significant differences between non-attenders and attenders. After adjustment for age, sex, diagnosis, employment, diabetes and family history, the mortality risk for non-attenders was 58 % greater than for attenders (HR = 1.58, 95 % CI: 1.16 to 2.15). Participants who attended less than 25 % of sessions had a mortality risk more than twice that of participants attending greater than or equal to 75 % of sessions (odds ratio [OR] = 2.57, 95 % CI: 1.04 to 6.38). This association was attenuated after adjusting for current smoking (OR = 2.06, 95 % CI: 0.80 to 5.29). The authors concluded that this study provided further evidence for the long-term benefits of CR in a contemporary, heterogeneous population. While a dose-response relationship may exist between the number of sessions attended and long-term mortality, this relationship does not occur independently of smoking differences. They stated that CR practitioners should encourage smokers to attend CR and provide support for smoking cessation.
The Centers for Medicare & Medicaid Services (CMS, 2010) state that cardiac rehabilitation (CR) programs must include a medical evaluation, a program to modify cardiac risk factors, with prescribed exercise, education and counseling. CMS allows for physicians to determine the time period over with CR services are provided as long as it falls within the covered time period identified in the CMS regulation. The regulation allows for coverage of up to 36 1-hour sessions over up to 36 weeks.
In 2014, CMS determined that the evidence was sufficient to expand coverage for cardiac rehabilitation services to beneficiaries with stable, chronic heart failure defined as patients with left ventricular ejection fraction of 35 % or less and New York Heart Association (NYHA) class II to IV symptoms despite being on optimal heart failure therapy for at least 6 weeks. Stable patients are defined as patients who have not had recent (less than or equal to 6 weeks) or planned (less than or equal to 6 months) major cardiovascular hospitalizations or procedures. Per CMS, CR sessions are limited to a maximum of two 1-hour session per day for up to 36 sessions over a period of 36 weeks. Furthermore, and additional 36 sessions may be warranted and approved by the Medicare contractor under section 1862(a)(1)(A) of the Social Security Act (CMS, 2014).
Gaalema et al (2015) noted that continued smoking after a cardiac event greatly increases mortality risk. Smoking cessation and participation in CR are effective in reducing morbidity and mortality. However, these 2 behaviors may interact; those who smoke may be less likely to access or complete CR. These researchers explored the association between smoking status and CR referral, attendance, and adherence. They carried out a systematic literature search examining associations between smoking status and CR referral, attendance and completion in peer-reviewed studies published through July 1, 2014. For inclusion, studies had to report data on outpatient CR referral, attendance or completion rates and smoking status had to be considered as a variable associated with these outcomes. A total of 56 studies met inclusion criteria. A history of smoking was associated with an increased likelihood of referral to CR. However, smoking status also predicted not attending CR and was a strong predictor of CR drop-out. The authors concluded that continued smoking after a cardiac event predicts lack of attendance in, and completion of CR. The issue of smoking following a coronary event deserves renewed attention.
Huang et al (2015) examined the effectiveness of telehealth intervention-delivered CR compared with center-based supervised CR. Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library and the Chinese BioMedical Literature Database (CBM), were searched to April 2014, without language restriction. Existing randomized controlled trials (RCTs), reviews, relevant conference lists and gray literature were checked. Randomized controlled trials that compared telehealth intervention delivered CR with traditional center-based supervised CR in adults with coronary artery disease (CAD) were included. Two reviewers selected studies and extracted data independently. Main clinical outcomes including clinical events, modifiable risk factors or other end-points were measured. A total of 15 articles reporting 9 trials were reviewed, most of which recruited patients with MI or re-vascularization. No statistically significant difference was found between telehealth interventions delivered and center-based supervised CR in exercise capacity (standardized mean difference (SMD) -0.01; 95 % CI: -0.12 to 0.10), weight (SMD -0.13; 95 % CI: -0.30 to 0.05), systolic and diastolic blood pressure (SBP and DBP) (mean difference (MD) -1.27; 95 % CI: -3.67 to 1.13 and MD 1.00; 95 % CI: -0.42 to 2.43, respectively), lipid profile, smoking (risk ratio (RR) 1.03; 95 % CI: 0.78 to 1.38), mortality (RR 1.15; 95 % CI: 0.61 to 2.19), quality of life and psychosocial state. The authors concluded that telehealth intervention-delivered CR does not have significantly inferior outcomes compared to center-based supervised program in low-to-moderate risk CAD patients. Telehealth intervention offers an alternative deliver model of CR for individuals less able to access center-based CR. Choices should reflect preferences, anticipation, risk profile, funding, and accessibility to health service.
In a Cochrane review, Taylor et al (2015) compared the effect of home-based and supervised center-based CR on mortality and morbidity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease. To update searches from the previous Cochrane review, these investigators searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 9, 2014), MEDLINE (Ovid, 1946 to Week 1 of October, 2014), EMBASE (Ovid, 1980 to Week 41 of 2014), PsycINFO (Ovid, to Week 2 of October, 2014), and CINAHL (EBSCO, to October 2014). They checked reference lists of included trials and recent systematic reviews. No language restrictions were applied. The authors concluded that this updated review supports the conclusions of the previous version of this review that home- and center-based forms of CR seem to be equally effective for improving the clinical and health-related quality of life outcomes in low risk patients after MI or re-vascularization, or with heart failure (HF). This finding, together with the absence of evidence of important differences in healthcare costs between the 2 approaches, supports the continued expansion of evidence-based, home-based CR programs. The choice of participating in a more traditional and supervised center-based program or a home-based program should reflect the preference of the individual patient. They stated that further data are needed to determine whether the effects of home- and center-based CR reported in these short-term trials can be confirmed in the longer term. A number of studies failed to give sufficient detail to assess their risk of bias.
Acute Coronary Syndrome
Rauch and colleagues (2016) noted that the prognostic effect of multi-component CR in the modern era of statins and acute re-vascularization remains controversial. These investigators evaluated the effect of CR on total mortality and other clinical end-points after an acute coronary event. Randomized controlled trials, retrospective controlled cohort studies (rCCSs) and prospective controlled cohort studies (pCCSs) evaluating patients after acute coronary syndrome (ACS), coronary artery bypass grafting (CABG) or mixed populations with CAD were included, provided the index event was in 1995 or later. Out of 18,534 abstracts, 25 studies were identified for final evaluation (RCT: n = 1; pCCS: n = 7; rCCS: n = 17), including n = 219,702 patients (after ACS: n = 46,338; after CABG: n = 14,583; mixed populations: n = 158,781; mean follow-up of 40 months). Heterogeneity in design, biometrical assessment of results and potential confounders was evident; CCSs evaluating ACS patients showed a significantly reduced mortality for CR participants (pCCS: HR 0.37, 95 % CI: 0.20 to 0.69; rCCS: HR 0.64, 95 % CI: 0.49 to 0.84; OR 0.20, 95 % CI: 0.08 to 0.48), but the single RCT fulfilling Cardiac Rehabilitation Outcome Study (CROS) inclusion criteria showed neutral results. These investigators noted that CR participation was also associated with reduced mortality after CABG (rCCS: HR 0.62, 95 % CI: 0.54 to 0.70) and in mixed CAD populations. The authors concluded that CR participation after ACS and CABG was associated with reduced mortality even in the modern era of CAD treatment. However, the heterogeneity of study designs and CR programs highlighted the need for defining internationally accepted standards in CR delivery and scientific evaluation.
Atrial Fibrillation
In a randomized study (the CopenHeartRFA Trial), Risom and colleagues (2016) examined the effects of comprehensive CR compared with usual care on physical activity and mental health for patients treated with catheter ablation for AF. The patients were randomized 1:1 stratified by paroxysmal or persistent AF and sex to CR consisting of 12 weeks physical exercise and 4 psycho-educational consultations plus usual care (CR group) versus usual care. The primary outcome was peak oxygen uptake (Vo2 peak). The secondary outcome was self-rated mental health measured by the Short Form-36 questionnaire. Exploratory outcomes were collected. A total of 210 patients were included (mean age of 59 years, 74 % men), 72 % had paroxysmal AF prior to ablation. Compared with usual care, the CR group had a beneficial effect on Vo2 peak at 4 months (24.3 ml/kg/min versus 20.7 ml/kg/min, p of main effect = 0.003, p of interaction between time and intervention = 0.020). No significant difference between groups on Short Form-36 was found (53.8 versus 51.9 points, p = 0.20); 2 serious AEs (AF in relation to physical exercise and death unrelated to rehabilitation) occurred in the CR group versus 1 in the usual care group (death unrelated to intervention) (p = 0.56). In the CR group 16 patients versus 7 in the usual care group reported non-serious AEs (p = 0.047). The authors concluded that comprehensive CR had a positive effect on physical capacity compared with usual care, but not on mental health. Moreover, CR caused more non-serious AEs.
In a Cochrane review, Risom and colleagues (2017) evaluated the benefits and harms of exercise-based CR programs, alone or with another intervention, compared with no-exercise training controls in adults who currently have atrial fibrillation (AF), or have been treated for AF. These investigators searched the following electronic databases; CENTRAL and the Database of Abstracts of Reviews of Effectiveness (DARE) in the Cochrane Library, Medline Ovid, Embase Ovid, PsycINFO Ovid, Web of Science Core Collection Thomson Reuters, CINAHL EBSCO, LILACS Bireme, and 3 clinical trial registers on July 14, 2016. They also checked the bibliographies of relevant systematic reviews identified by the searches. They imposed no language restrictions. These researchers included RCTs that examined exercise-based interventions compared with any type of no-exercise control. They included trials with adults aged 18 years or older with AF, or post-treatment for AF. Two authors independently extracted data. They assessed the risk of bias using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. They assessed clinical and statistical heterogeneity by visual inspection of the forest plots, and by using standard Chi² and I² statistics. These researchers performed meta-analyses using fixed-effect and random-effects models; they used SMDs where different scales were used for the same outcome. They assessed the risk of random errors with trial sequential analysis (TSA) and used the GRADE methodology to rate the quality of evidence, reporting it in the “Summary of findings” table. A total of 6 RCTs with 421 patients with various types of AF were included in this review. All trials were conducted between 2006 and 2016, and had short follow-up (8 weeks to 6 months). Risks of bias ranged from high risk to low risk. The exercise-based CR programs in 4 trials consisted of both aerobic exercise and resistance training, in 1 trial consisted of Qi-gong (slow and graceful movements), and in another trial, consisted of inspiratory muscle training. For mortality, very low-quality evidence from 6 trials suggested no clear difference in deaths between the exercise and no-exercise groups (RR 1.00, 95 % CI: 0.06 to 15.78; participants = 421; I² = 0 %; deaths = 2). Very low-quality evidence from 5 trials suggested no clear difference between groups for serious adverse events (AEs) (RR 1.01, 95 % CI: 0.98 to 1.05; participants = 381; I² = 0 %; events = 8). Low-quality evidence from 2 trials suggested no clear difference in health-related quality of life (QOL) for the Short Form-36 (SF-36) physical component summary measure (MD 1.96, 95 % CI: -2.50 to 6.42; participants = 224; I² = 69 %), or the SF-36 mental component summary measure (MD 1.99, 95 % CI: -0.48 to 4.46; participants = 224; I² = 0 %). Exercise capacity was assessed by cumulated work, or maximal power (Watt), obtained by cycle ergometer, or by 6-minute walking test (6MWT), or ergo-spirometry testing measuring VO2 peak. These researchers found moderate-quality evidence from 2 studies that exercise-based CR increased exercise capacity, measured by VO2 peak, more than no exercise (MD 3.76, 95 % CI: 1.37 to 6.15; participants = 208; I² = 0 %); and very low-quality evidence from 4 studies that exercise-based rehabilitation increased exercise capacity more than no exercise, measured by the 6MWT (MD 75.76, 95 % CI: 14.00 to 137.53; participants = 272; I² = 85 %). When these investigators combined the different assessment tools for exercise capacity, they found very low-quality evidence from 6 trials that exercise-based rehabilitation increased exercise capacity more than no exercise (SMD 0.86, 95 % CI: 0.46 to 1.26; participants = 359; I² = 65 %). Overall, the quality of the evidence for the outcomes ranged from moderate to very-low. The authors concluded that due to few randomized patients and outcomes, they could not evaluate the real impact of exercise-based CR on mortality or serious AEs. The evidence showed no clinically relevant effect on health-related QOL. Pooled data showed a positive effect on the surrogate outcome of physical exercise capacity, but due to the low number of patients and the moderate to very low-quality of the underpinning evidence, the authors could not be certain of the magnitude of the effect. Moreover, they stated that future high-quality randomized trials are needed to evaluate the benefits and harms of exercise-based CR for adults with AF on patient-relevant outcomes.
Kato and associates (2019) stated that the safety and effectiveness of CR for patients with persistent AF who restored sinus rhythm after catheter ablation remains unclear. In a RCT, these researchers examined the effects of CR on exercise capacity, inflammatory status, cardiac function, and safety in patients with persistent AF who had catheter ablation. A total of 61 patients treated with catheter ablation for persistent AF (men, 80 %; mean age of 66 ± 9 years) were analyzed; 30 patients underwent CR (rehabilitation group), whereas the remaining 31 patients received usual care (usual care group). The CR group underwent endurance and resistance training with moderate intensity, at least thrice-weekly for 6 months; 6MWD, muscle strength, serum high-sensitivity C-reactive protein (CRP), plasma pentraxin 3, LVEF and AF recurrence were assessed at baseline and at 6-month follow-up. In the CR group, significant increases in the 6MWD, handgrip strength, leg strength and LVEF and significant decreases in high-sensitivity CRP and plasma pentraxin 3 concentrations were observed at 6-month follow-up compared with baseline (all p < 0.05). No significant changes were observed in the usual care group. During the 6-month follow-up period, the number of patients with AF recurrence was 6 (21.4 %) in the CR group and 8 (25.8 %) in the usual care group (RR, 0.83; 95 % CI: 0.33 to 2.10). The authors concluded that CR improved exercise capacity without increasing the risk for AF recurrence. It may also be effective in managing systemic inflammatory status and systolic LV function in patients with persistent AF treated with catheter ablation.
The authors stated that this study had several drawbacks. First, the single-center design and the relatively small number of subjects (n = 30 in the CR group) were major limitations. Despite the absence of statistically significant differences in patient characteristics between the 2 groups, the effect of randomization might not have been perfect because of the small sample size. Furthermore, log-rank tests in this study might have the probability of making a type II error. On the other hand, the primary outcome of the present study was exercise capacity and sample size for the primary outcome was calculated using 6MWD data from a previous study. In addition, it was difficult to enroll statistically enough patients to demonstrate a difference in AF recurrence because patients with paroxysmal AF were ineligible and the exclusion criteria were strict. Second, the subjects were not blinded for the exercise intervention. This might have affected their everyday lifestyle (e.g., other activity and diet). Third, there was a possibility for detection bias regarding AF recurrence because AF recurrence was evaluated only 3 times using a 12-lead ECG and twice using a 24-hour ECG during the study. Using an implanted loop recorder to continuously examine AF recurrence would have been ideal. Fourth, the lack of information on QOL was another limitation in the present study because QOL was becoming an increasingly important measure when evaluating interventions for AF patients. Fifth, a short-term follow-up period of 6 months was also a limitation in this study. Pathak et al (2014) demonstrated that aggressive risk factor management improved the long-term success of AF ablation; thus, a longer follow-up might have reinforced the value of the study. Sixth, as the values of LVEF and inflammatory markers at baseline and follow-up were within the normal range in both groups, it was unclear if changes in these parameters by CR had clinical significance, such as AF recurrence or their prognosis in the future. Finally, given that this trial included only patients with persistent AF, it was unclear if CR would have the same effect among non-persistent AF patients. These researchers noted that because of these limitations, their findings require confirmation from larger samples, multi-center studies, possibly using an outcome measurement without detection bias.
In long-term follow-up of the randomized CopenHeartRFA Trial, Risom and wo-workers (2020) examined outcomes at 12 as well as 24 months following participation in a multi-disciplinary CR program plus usual care compared with usual care alone for patients treated for AF with catheter ablation. Patients were enrolled and outcome examined at the hospital and the intervention were performed at the hospital or at local rehabilitation centers. Interventions included a 6-month CR program consisting of physical exercise and psycho-educational consultations plus usual care or usual care alone. Physical capacity was measured by Vo2 peak at 12 months, and patient-reported outcomes on perceived health, anxiety, and depression were collected by validated questionnaires at 12 and 24 months. Information on hospital admissions and mortality was collected through national registers up to 24 months. Mean Vo2 peak was higher at 12 months in the CR group (25.82 ml/kg/min) versus usual care group (22.43 ml/kg/min, p = 0.003). A lower proportion of patients had high levels of anxiety at 24 months in the CR group compared to usual care (12 % versus 24 %, p = 0.004). There was no difference in mortality or hospital admissions at 24 months between the 2 groups. The authors concluded that this long-term follow-up of a comprehensive multi-disciplinary CR program for patients treated for AF with catheter ablation found sustained improvements with respect to physical capacity and anxiety compared to usual care but no difference on mortality or hospital admission.
Benjamin et al (2021) noted that there has been sustained focus on the secondary prevention of coronary heart disease and HF; yet, apart from stroke prevention, the evidence base for the secondary prevention of AF recurrence, AF progression, and AF-related complications is modest. Although there are multiple observational studies, there are few large, robust, randomized trials providing definitive effective approaches for the secondary prevention of AF. Given the increasing incidence and prevalence of AF nationally and internationally, the AF field needs transformative research and a commitment to evidenced-based secondary prevention strategies. These investigators reported on a National Heart, Lung, and Blood Institute virtual workshop directed at identifying knowledge gaps and research opportunities in the secondary prevention of AF. Once AF has been detected, lifestyle changes and novel models of care delivery may contribute to the prevention of AF recurrence, AF progression, and AF-related complications. Although benefits observed in small subgroups, cohort studies, and selected randomized trials were impressive, the widespread effectiveness of AF secondary prevention strategies remains unknown, calling for development of scalable interventions suitable for diverse populations and for identification of subpopulations who may particularly benefit from intensive management. The authors identified critical research questions for 6 topics relevant to the secondary prevention of AF:
- Weight loss
- Alcohol intake, smoking cessation, and diet
- Cardiac rehabilitation
- Approaches to sleep disorders
- Integrated, team-based care
- Non-anticoagulant pharmacotherapy.
Aoyama et al (2021) noted that few studies have examined the safety and effectiveness of CR in patients with AF who have undergone AF ablation. These researchers examined the feasibility of additional CR following AF ablation in patients with a reduced LVEF. A total of 54 patients with HF and a reduced LVEF (HFrEF) (LVEF less than 50 %; age of 67.1 ± 11.6 years; 43 men) who underwent initial AF ablation procedures were included; 14 (25.9 %) patients underwent CR (rehabilitation-group) and the remaining 40 (74.1 %) did not (non-rehabilitation-group) after the procedure. The rehabilitation-group patients were relatively older, more likely women (p = 0.024), and had more likely a history of an HF hospitalization (p < 0.01) and cardiac device implantation (p = 0.041). The baseline LVEF was significantly lower (p = 0.043) and brain natriuretic peptide (BNP) (p < 0.01) and CRP (p < 0.01) values were significantly higher in the rehabilitation-group. The 6MWD significantly improved after 21.4 ± 11.5 days of CR during hospitalization (226.1 ± 155.9 versus 398.1 ± 77.5 m, p = 0.016) without any AEs. During an 18.9 ± 6.3 months follow-up period, the freedom from AF recurrence (p = 0.52) and re-hospitalizations due to HF (p = 0.63) were similar between the 2 groups. No death or strokes were observed. During the follow-up period, the LVEF significantly improved similarly in both groups, and the change in the BNP and CRP values significantly decreased in the rehabilitation-group. The authors concluded that despite the rehabilitation-group patients having a more severe HF status, the clinical outcomes and AF freedom were similar between the 2 groups, suggesting the favorable impact of CR following AF ablation in HFrEF patients.
Buckley et al (2024) noted that AF disrupts the heart's rhythm via many small re-entry circuits in the atrial tissue, resulting in irregular atrial contractions. The condition poses significant health risks, including increased stroke risk, HF, and reduced QOL. Given the complexity of AF and its growing incidence worldwide, exercise-based CR (ExCR) may provide additional benefits for patients with AF or those undergoing routine treatment for the condition. In a Cochrane review, these researchers examined the benefits and harms of ExCR compared with non-exercise controls for individuals who currently have AF or who have been treated for AF. They searched the following electronic databases: CENTRAL in the Cochrane Library, Medline Ovid, Embase Ovid, PsycINFO Ovid, Web of Science Core Collection Thomson Reuters, CINAHL EBSCO, LILACS BIREME, as well as 2 clinical trial registers on March 24, 2024; no language restrictions was imposed. These investigators included RCTs that examined ExCR interventions compared with any type of non-exercise control. They included adults 18 years of age or older with any subtype of AF or those who had received treatment for AF. A total of 5 review authors independently screened and extracted data in duplicate. They examined risk of bias using Cochrane's RoB 1 tool as outlined in the Cochrane Handbook for Systematic Reviews of Interventions. These researchers evaluated clinical and statistical heterogeneity by visual inspection of the forest plots and by using standard Chi² and I² statistics. They carried out meta-analyses by means of random-effects models for continuous and dichotomized outcomes; and calculated SMDs where different scales were used for the same outcome. They employed the GRADE approach to evaluate the certainty of the evidence. These investigators included a total of 20 RCTs entailing 2,039 subjects with AF. All studies were carried out between 2006 and 2024, with a follow-up period ranging from 8weeks to 5 years. These researchers examined the certainty of evidence as moderate-to-very low. A total of 5 trials assessed comprehensive ExCR programs, which included educational or psychological interventions, or both; the remaining 15 trials compared exercise-only CR with controls. The overall risk of bias in the included studies was mixed. Details on random sequence generation, allocation concealment, and use of intention-to-treat (ITT) analysis were typically poorly reported. Evidence from 9 trials (n = 1,173) suggested little to no difference in mortality between ExCR and non-exercise controls (RR 1.06, 95 % CI: 0.76 to 1.49; I² = 0 %; 101 deaths; low-certainty evidence). Based on evidence from 10 trials (n = 825), ExCR may have little to no effect on SAEs (RR 1.30, 95 % CI: 0.63 to 2.67; I² = 0 %; 28 events; low-certainty evidence). Evidence from 4 trials (n = 378) showed that ExCR likely reduced AF recurrence (measured via Holter monitoring) compared to controls (RR 0.70, 95 % CI: 0.56 to 0.88; I² = 2 %; moderate-certainty evidence). ExCR may reduce AF symptom severity (MD -1.59, 95 % CI: -2.98 to -0.20; I² = 61 %; n = 600; low-certainty evidence); likely reduced AF symptom burden (MD -1.61, 95 % CI: -2.76 to -0.45; I² = 0 %; n = 317; moderate-certainty evidence); may reduce AF episode frequency (MD -1.29, 95 % CI: -2.50 to -0.07; I² = 75 %; n = 368; low-certainty evidence); and likely reduced AF episode duration (MD -0.58, 95 % CI: -1.14 to -0.03; I² = 0 %; n = 317; moderate-certainty evidence), measured via the AF Severity Scale (AFSS) questionnaire. Moderate-certainty evidence from 6 trials (n = 504) showed that ExCR likely improved the mental component summary measure in health-related QOL (HR-QOL) of the SF-36 (MD 2.66, 95 % CI: 1.22 to 4.11; I² = 2 %), but the effect of ExCR on the physical component summary measure was very uncertain (MD 1.75, 95 % CI: -0.31 to 3.81; I² = 52 %; very low-certainty evidence). ExCR also may improve individual components of HR-QOL (general health, vitality, emotional role functioning, and mental health) and exercise capacity (peak oxygen uptake (VO2peak) and 6MWT) following ExCR. The effects of ExCR on serious AEs and exercise capacity were consistent across different models of ExCR delivery: center compared to home-based, exercise dose, exercise only compared to comprehensive programs, and aerobic training alone compared to aerobic plus resistance programs. Using uni-variate meta-regression, there was evidence of significant association between location of trial and length of longest follow-up on exercise capacity.
The authors concluded that due to few randomised participants and typically short-term follow-up, the impact of ExCR on all-cause mortality or serious AEs for patients with AF is uncertain. ExCR likely improved AF-specific measures including reduced AF recurrence, symptom burden, and episode duration, as well as the mental components of HR-QOL. In addition, ExCR may improve AF symptom severity, episode frequency, and VO2peak. Moreover, these researchers stated that future high-quality RCTs are needed to examine the benefits of ExCR for individuals with AF on PROMs including AF symptom severity and burden, AF recurrence, AF-specific QOL, and clinical events such as mortality, re-admissions, and serious AEs. These investigators noted that high-quality studies are needed to examine how AF subtype and clinical setting (i.e. primary and secondary care) may influence ExCR effectiveness.
Following Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension
Fukui and co-workers (2016) determined the safety and effectiveness of CR initiated immediately following balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) who presented with continuing exercise intolerance and symptoms on effort even after a course of BPA; 2 to 8 sessions/patient. A total of 41 consecutive patients with inoperable CTEPH who underwent their final BPA with improved resting mean pulmonary arterial pressure (PAP) of 24.7±5.5 mm Hg and who suffered remaining exercise intolerance were prospectively studied. Participants were divided into 2 groups just after the final BPA (6.8 ± 2.3 days): (i) patients with (CR group, n = 17) or without (non-CR group, n = 24) participation in a 12-week CR of 1-week in-hospital training followed by an 11-week out-patient program. Cardiopulmonary exercise testing (CPET), hemodynamics, and quality of life (QOL) were assessed before and after CR. No significant between-group differences were found for any baseline characteristics. At week 12, peak oxygen uptake (VO2), per cent predicted peak VO2 (70.7 ± 9.4 % to 78.2 ± 12.8 %, p < 0.01), peak work-load, and oxygen pulse significantly improved in the CR group compared with the non-CR group, with a tendency towards improvement in mental health-related QOL. Quadriceps strength and heart failure (HF) symptoms (WHO functional class, 2.2 to 1.8, p = 0.01) significantly improved within the CR group. During the CR, no patient experienced adverse events (AEs) or deterioration of right-sided HF or hemodynamics as confirmed via right heart catheterization. The authors concluded that the combination of BPAs and subsequent CR for inoperable CTEPH additively ameliorated exercise intolerance to near-normal levels and improved HF symptoms, with a tendency towards improvement in mental health-related QOL. They stated that this promising new treatment strategy did not require a prolonged hospital stay for initial in-hospital training and did not lower patient compliance; however, further large, randomized, multi-center studies are needed to confirm the present findings.
- it lacked randomization during group assignment, although it was prospectively designed with a control group. Thus, they could not exclude the possibility that selection bias affected the present results. However, no significant between-group differences were found in any baseline characteristics, which might strengthen the value of the present results,
- this study was implemented in a single center, although the center is one of the largest pulmonary hypertension centers in Japan with experienced rehabilitation centers. These results should be confirmed in a large, randomized, multi-center study,
- the increase in 6-minute walk distance (6MWD) in the CR group did not reach statistical significance -- this was inconsistent with previous studies with patients with CTEPH.
It was possible that these patients with CR walked much better in the baseline 6MWD examination (498 ± 96 m) than the patients with CTEPH in previous studies (353 to 453 m), because these patients had already undergone BPAs before group assignment, in addition to PH-specific therapies. This was also supported by the findings that exercise training might be more effective in patients with a lower 6MWD, rather than those who have a near-normal 6MWD (greater than 550 m) and that 6MWD was less sensitive to increases in peak VO2 at distances greater than 500 m, (iv) VO2 at anaerobic threshold (AT) did not significantly improve after CR, consistent with the findings of Yuan et al who conducted a systematic review and meta-analysis on exercise training for PH. In addition, these researchers could not accurately determine the AT level in the pre-interventional and/or post-interventional CPET in 5 of 17 patients in the CR group due to ventilatory oscillation-like changes or increased ventilatory drives even at rest, implying that the AT level was unreliable in this population, and (v) physical-related QOL scores were unchanged after CR, which was inconsistent with previous studies. The authors could explain this discrepancy by their preliminary data that physical-related QOL scores in their patients had already improved to a certain degree before CR via BPA alone (data not shown), as well as hemodynamics and functional capacity.
Following Heart Valve Surgery
Sibilitz and colleagues (2016) stated that the evidence for CR after valve surgery remains sparse. Thus, current recommendations are based on patients with ischemic heart disease. In a randomized clinical trial, these researchers examined the effects of CR versus usual care after heart valve surgery. The trial was an investigator-initiated, randomized superiority trial (The CopenHeartVR trial, VR; valve replacement or repair). They randomized 147 patients after heart valve surgery 1:1 to 12 weeks of CR consisting of physical exercise and monthly psycho-educational consultations (intervention) versus usual care without structured physical exercise or psycho-educational consultations (control). Primary outcome was physical capacity measured by VO2 peak and secondary outcome was self-reported mental health measured by Short Form-36. A total of 76 % of participants were men, mean age of 62 years, with aortic (62 %), mitral (36 %) or tricuspid/pulmonary valve surgery (2 %). Cardiac rehabilitation compared with control had a beneficial effect on VO2 peak at 4 months (24.8 mL/kg/min versus 22.5 mL/kg/min, p = 0.045); but did not affect Short Form-36 Mental Component Scale at 6 months (53.7 versus 55.2 points, p = 0.40) or the exploratory physical and mental outcomes. Cardiac rehabilitation increased the occurrence of self-reported non-serious AEs (11/72 versus 3/75, p = 0.02). The authors concluded that CR following heart valve surgery significantly improved VO2 peak at 4 months but had no effect on mental health and other measures of exercise capacity and self-reported outcomes. Moreover, they stated that further research is needed to justify CR in this patient group.
Following Repair of Sinus Venosus Atrial Septal Defects
A Medscape review on “Sinus venosus atrial septal defects” (Satou, 2015) did not mention CR. Furthermore, an UpToDate review on “Surgical and percutaneous closure of atrial septal defects in adults” (Connolly, 2017) does not mention CR as a management tool.
Cardiac Rehabilitation Following Septal Myectomy
Septal myectomy is one treatment option that is performed surgically via open-heart in order to reduce the muscle thickening that occurs in symptomatic patients with hypertrophic cardiomyopathy (HCM) refractory to medications, or with left ventricular outflow tract (LVOT) obstruction severely restricting blood ejection from the heart. Surgical septal myectomy relieves LVOT obstruction by directly removing the thickened septal wall. The surgical septal myectomy involves performing a thoractomy, with individual being placed on cardiopulmonary bypass. Surgical septal myectomy results in resolution of the LVOT gradient and improvmeent in heart failure symptoms in most individuals. Long-term outcomes also includes reductions in implantable cardioverter-defibrillator (ICD) discharges and improvement in left atrial volumes and pulmonary hypertension (Maron, 2019).
Redwood et al (1979) noted that the effect of left ventriculo-myotomy and myectomy on exercise capacity and cardiac function in patients with obstructive hypertrophic cardiomyopathy has not previously been determined. In this study, a total of 29 patients were evaluated during graded treadmill exercise before and after operation. Post-operatively, 27 of 29 patients reported symptomatic improvement and had greatly reduced left ventricular outflow gradient; 25 of 28 patients (89 %) attained higher exercise levels after operation, and this was accompanied by an increase in total body oxygen consumption from 16 to 21 ml/min per kg (p < 0.005). A significant increase in cardiac index during maximal exercise also accompanied this improved exercise performance (5.0 to 5.7 L/min/m2, p < 0.05). The increase in maximal cardiac index was associated with greater desaturation of mixed venous blood (34 to 24 %, p < 0.02) in patients with pre-operative angina. At a given level of mixed venous oxygen saturation (30 %), overall mean cardiac index was higher post-operatively (4.6 to 5.2 L/min/m2, p < 0.05). The authors concluded that these findings suggested that, although several mechanisms probably contributed to symptomatic improvement after myotomy and myectomy, enhanced cardiac performance played an important role in the majority of patients.
Franz et al (2008) stated that infective endocarditis due to viridans streptococci is associated with a mortality of 5 to 10 %. Even today, it remains difficult to diagnose it at an early stage, to select a sufficient antibiotic therapy and to choose the right time for surgical intervention. These investigators reported on the case of a 37-year old man who presented with anemia, fever, adynamia and a loud systolic murmur over the base of the heart. Blood culture data were positive for Streptococcus mitis. Trans-thoracic echocardiography (TTE) revealed an endocarditis of the aortic and mitral valve with regurgitations as well as a hypertrophic obstructive cardiomyopathy. The hemodynamically stable patient was treated with penicillin G, gentamicin and verapamil. Because of an extension of valve vegetations and a decline in the hemodynamic situation with an incipient sepsis, the patient was surgically treated urgently by replacement of the aortic and mitral valve as well as a Morrow septal myectomy. A post-operative sepsis required the application of high catecholamine doses. Because of a respiratory insufficiency, a prolonged mechanical ventilation was required. Finally, the patient could be discharged for in-hospital rehabilitation. The authors concluded that the indication for surgical therapy in patients with endocarditis of the aortic and mitral valve as well as hypertrophic obstructive cardiomyopathy should be critically discussed with regard to the patient's age, the aims of conservative therapy, and the consequences of a surgical intervention. If there were any indices of a disease progress in spite of antibiotic therapy, patients should be subjected to cardiac surgery immediately.
Although there is insufficient evidence via randomized controlled clinical trials to support cardiac rehabilitation specifically for surgical septal myectomy, cardiac rehabilitation programs' efficacy has been established in other open-heart surgical indications (e.g. CABG, heart transplant).
Individuals With Lymphoma Undergoing Autologous Hematopoietic Stem Cell Transplantation
Rothe and colleagues (2018) noted that worldwide more than 50,000 hematopoietic stem cell transplants (HSCTs) are performed annually; and HSCT patients receive multiple cardiotoxic therapies (chemotherapy and radiation therapy) in addition to severe physical deconditioning during hospital admission. These researchers hypothesized that guided exercise in a CR program following autologous HSCT is a safe and feasible intervention. This was a pilot project to assess for safety, feasibility and impact of 8 weeks of CR in HSCT patients following transplant. Consecutive patients with lymphoma underwent standard activity protocol testing before HSCT, at 6 weeks following HSCT (prior to CR), and at 14 weeks following HSCT (at completion of CR), consisting of grip strength (GS), gait speed (GtS), timed up-and-go (TUG), and 6-minute walk test (6MWT); CR consisted of 8 weekly visits for guided exercise. Activity tolerance protocol data of 30 patients (24 male, 6 female) from December 2014 to December 2016 were analyzed using repeated measures (analysis of variance [ANOVA]) to observe for changes in GS, GtS, TUG, and 6MWT. Statistically significant improvements were found in GS (p < 0.005), GtS (p = 0.02), and 6MWT (p = 0.001). These improvements showed that guided CR-based exercise may assist HSCT survivors to meet or even surpass baseline exercise levels and improve physical functioning. There were no AEs (i.e., death or injury) during the study period; 57 % of referred patients participated in CR, exceeding documented CR adherence in cardiac populations. The authors concluded that the addition of CR-based exercise programming in HSCT survivorship care of patients with lymphoma was a safe and feasible intervention to assist in recovery following transplant. These preliminary findings need to be validated by well-designed studies.
Symptomatic Individuals with Non-Obstructive Coronary Artery Disease
Kissel and colleagues (2018) stated that non-obstructive coronary artery disease (NOCAD) on coronary angiography is a common finding in patients with stable angina. Angina in NOCAD patients is thought to be caused by endothelial dysfunction of the epicardial coronary arteries and/or the microvasculature. Treatment is empiric, and 30 % of patients remain symptomatic in spite of therapy. It is well known that physical exercise can improve endothelial function. These investigators evaluated the evidence on effects of physical exercise in NOCAD patients with angina. They performed a literature search (up to March 13, 2018) using the following search terms: syndrome X, microvascular angina, non-obstructive coronary artery disease and exercise training, cardiac rehabilitation, endothelial function. All original publications which examined the effect of a CR program or exercise training (ET) on patients with angina and NOCAD. A total of 8 studies, of which 4 were RCTs, examined 218 participants, 162 in an intervention and 56 in control groups. Most patients were women (97.7 %). Exercise programs varied from 8 weeks to 4 months at moderate intensity and some included relaxation therapy. The studies examined the effect of CR on exercise capacity, QOL, and perfusion defects. CR increased exercise capacity, oxygen uptake, symptom severity, and QOL; myocardial perfusion improved. The authors concluded that CR appeared to be beneficial in symptomatic patients with NOCAD, improving exercise capacity and QOL and reducing severity of symptoms and myocardial perfusion defects. Moreover, these researchers stated that data were limited to a small number of predominantly female patients. They stated that further larger trials with inclusion of men are needed to determine the optimal rehabilitation protocols and define its long-term benefits.
The authors stated that this study had several drawbacks. First, the included studies were all small with low patient numbers in each treatment group, thus limiting statistical power. In addition, not all of the studies were randomized. Second, the majority of studies included only women (97.7 %). Although cardiac syndrome X is more common in women, it is well established that it also occurs in men, with up to 30 % of men with SA presenting for coronary angiogram, have NOCAD. Given that the studies were limited to women, these investigators could only speculate whether ET has the same positive effect in men. Outcome measures in the reported trials consisted mostly of parameters for exercise capacity, easily measurable physical values, and QOL assessed by questionnaires. All outcomes were evaluated in the short-term, directly after completion of the CR program. No data were available on the long-term effects of CR programs in NOCAD, and whether the beneficial effect was sustained over time. Furthermore, it would be interesting to find out whether this transferred into hard end-points like less frequent hospitalization, lower treatment costs, and possibly an improved outcome. For a long time, symptomatic patients with NOCAD were assured of the benign nature of their condition. However, recent data pointed towards an adverse outcome of these patients in regard to MI, cardiovascular, and all-cause mortality. Thus, it would be intriguing to examine if CR also led to an improved cardiovascular outcome in this patient population. These researchers stated that current studies on the effect of ET in symptomatic patients with NOCAD are promising but larger, randomized studies with inclusion of men are needed to evaluate the benefit of ET on hard end-points and the long-term effect of ET. Furthermore, a study protocol should include randomized groups to determine the optimal training protocol in regard to training intensity, duration, and inclusion of relaxation techniques. Furthermore, it would be of interest to include vascular function studies to gain further insight into the pathophysiological mechanisms.
Diabetes Mellitus
Cardiac rehabilitation (CR) programs include interventions aimed at improving diabetes mellitus (DM) control (e.g., education, blood glucose monitoring, supervised exercise, and ECG monitoring for phase II sessions). One of the core components of CR/secondary prevention program includes diabetes management. CR programs monitor blood glucose (BG) levels before/after exercise sessions and instruct patients regarding identification and treatment of post-exercise hypoglycemia. Because the AACVPR recommends avoiding vigorous exercise before blood glucose has been adequately controlled, CR programs follow protocols/guidelines that monitor and check diabetic patients before and after exercise, and will prohibit patients from exercise if blood glucose level is outside of set parameters (Balady et al, 2000; McCulloch, 2019). According to AACVPR, “monitoring BG levels is vital for the long-term maintenance of glycemic control and is especially important during exercise given that beta-blocker therapy can mask the onset of an impending insulin reaction. Monitoring BG levels during exercise may also provide positive feedback regarding the regulation or progression of the exercise prescription, which may result in subsequent long-term adherence to exercise. This is particularly important since exercise is a cornerstone of treatment for diabetes” (Human Kinetics, 2019).
An UpToDate review of the “Effects of exercise in adults with diabetes mellitus” (McCulloch, 2019) state that in the absence of contraindications (e.g., moderate to severe proliferative retinopathy), people with type 1 and 2 diabetes should be encouraged to perform resistance training (exercise with free weights or weight machines) at least twice per week; however, vigorous exercise should be avoided in the presence of substantial hyperglycemia (≥250 mg/dL [13.9 mmol/L]) or ketosis. The authors state that it is not necessary to defer exercise based on milder hyperglycemia, as long as the patient feels well and there is no ketonemia or ketonuria. It should be noted that patients can be at risk of late hypoglycemia (i.e., 4-8 hours after the termination of exercise); however, this can usually be avoid by ingesting slowly absorbed carbohydrates immediately after exercise. “Inadequate replacement of carbohydrate before, during, and after exercise is the most common cause of exercise-associated hypoglycemia in patients taking insulin.”
Jimenez-Navarro et al (2017) state that cardiac rehabilitation (CR) participation after percutaneous coronary intervention (PCI) is associated with lower all‐cause mortality rates in patients with DM, to a similar degree as for those without DM. The authors noted that CR participation has been lower in patients with DM, suggesting the need to identify and correct the barriers to CR participation for this higher‐risk group of patients. The authors conducted a retrospective analysis of patients (n = 700) with DM who underwent PCI in a single center facility between 1994 and 2010, assessing the impact of CR participation on clinical outcomes. The endpoints of their study were to evaluate the impact of CR on cardiovascular events and mortality after PCI in patients with DM, and to compare the relative impact of CR on these outcomes in patients with and without DM. The authors found that CR participation was significantly lower in patients with DM (38 %, 263/700) compared with those who did not have DM (45 %, 1,071/2,379; p = 0.004). Using propensity score adjustment, the authors found that in patients with DM, CR participation was associated with significantly reduced all‐cause mortality (p = 0.002) and composite end-point of mortality, myocardial infarction, or re-vascularization (p = 0.037), during a median follow‐up of 8.1 years. In patients without DM, CR participation was associated with a significant reduction in all‐cause mortality (p < 0.001) and cardiac mortality (p = 0.024). This study was limited by the retrospective nature of the data, and was conducted in a single-center facility. In addition, the study cohort was primarily White, non‐Hispanic individuals; thus, may not be representative of other populations. However, the authors noted that data from the study location was identified as being a representative community‐based sample of data, with characteristics that were similar to those of other primarily White populations within the U.S. The authors concluded that these findings highlighted the benefits of CR, while supporting efforts, including the development and dissemination of clinical practice guidelines, performance measures, and policy initiatives, that were aimed at increasing CR participation after PCI. Methods to improve delivery of CR after PCI to patients with DM appeared to be warranted.
Cardiac Rehabilitation Following Pericardiectomy for Calcified Constrictive Pericarditis
Drahosova (1989) noted that between 1967 to 1986 in the Czechoslovak State spa Sliac, a total of 961 (48.15 %) men and 1,035 (51.85 %) women after surgical operations on the heart were followed-up during the 2nd rehabilitation stage. The operations were made because of the following indications: acquired rheumatic valvular defects (n = 1,208; 60.52 %), congenital heart disease (n = 461; 23.10 %), ischemic heart disease (n = 260; 13.03 %), myxomas and thrombi of the left atrium (n = 31; 1.55 %), pericardiectomy (n = 36; 1.80 %). As to surgical operations, commissurotomy and commissurolysis were performed in 724 (36.27 %); an artificial prosthesis was implanted in 330 (16.53 %), homo-transplants in 151 (7.57 %) auto-transplants in 3 (0.15 %), aorto-coronary by-pass/re-vascularization in 260 (13.03), surgical operations on account of congenital heart disease, thrombi and myxomas of the left atrium were performed in 492 (24.65 %) of the patients. Rehabilitation care comprised in addition to remedial exercise a therapeutic regime, clinical and laboratory examinations, diet therapy, medicamentous and physical therapy and carbon dioxide (CO2) baths. After rehabilitation care objective improvement was recorded in 850 (42.59 %), subjective improvement in 953 (47.74 %), no change in 143 (7.16 %), deterioration in 47 (2.35 %), and 3 patients (0.15 %) died.
Wachter and Hasenfuss (2010) presented the case of a 46-year old man with progressive dyspnea on exertion and severe headache while having the head lowered. Clinically, the patient showed left-sided pleural effusion, jugular venous distension, and a congested liver. During cardiologic work-up, echocardiography, combined left/right heart catheterization and magnetic resonance imaging (MRI) established the diagnosis of constrictive pericarditis. Under conservative medical treatment, the patient again developed cardiac decompensation and, thus, a peri-cardectomy was performed. Immediately after surgery, symptoms diminished and exercise tolerance increased. The patient was currently in CR. The authors concluded that constrictive pericarditis is a rare differential diagnosis of right heart failure. Especially in patients with congested inferior vena cava, but normal systolic left ventricular function and normal function of the cardiac valves, constrictive pericarditis should be considered as a differential diagnosis.
Ponomarev et al (2018) stated that constrictive pericarditis (CP) is the final stage of a chronic inflammatory process characterized by fibrous thickening and calcification of the pericardium that impairs diastolic filling, reduces cardiac output, and ultimately leads to HF. These researchers presented a clinical case of CP in a patient with rare inherited bleeding disorder -- factor VII deficiency. Heart failure due to CP was suspected based on clinical symptoms, results of ultrasonic and radiological investigations. The diagnosis was verified by the results of cardiac MRI. Peri-cardectomy was performed resulting in significant improvement in the patient's condition. Cardiac rehabilitation was not mentioned and was not listed as one of the keywords for this study.
Cardiac Rehabilitation Following Stroke
Prior and colleagues (2011) tested feasibility and effectiveness of 6-month outpatient comprehensive cardiac rehabilitation (CCR) for secondary prevention after transient ischemic attack or mild, non-disabling stroke. Consecutive consenting subjects having sustained a transient ischemic attack or mild, non-disabling stroke within the previous 12 months (mean of 11.5 weeks; event-to-CCR entry) with greater than or equal to 1 vascular risk factor, were recruited from a stroke prevention clinic providing usual care. These researchers measured 6-month CCR outcomes following a prospective cohort design. Of 110 subjects recruited from January 2005 to April 2006, 100 subjects (mean age of 64.9 years; 46 women) entered and 80 subjects completed CCR. These investigators obtained favorable, significant intake-to-exit changes in: aerobic capacity (+31.4 %; p < 0.001), total cholesterol (-0.30 mmol/L; p = 0.008), total cholesterol/high-density lipoprotein (-11.6 %; p < 0.001), triglycerides (-0.27 mmol/L; p = 0.003), waist circumference (-2.44 cm; p < 0.001), body mass index (-0.53 kg/m(2); p = 0.003), and body weight (-1.43 kg; p = 0.001). Low-density lipoprotein (-0.24 mmol/L), high-density lipoprotein (+0.06 mmol/L), systolic (-3.21 mm Hg) and diastolic (-2.34 mm Hg) blood pressure changed favorably, but non-significantly. A significant shift toward non-smoking occurred (p = 0.008). Compared with intake, 11 more individuals (25.6 % increase) finished CCR in the lowest-mortality risk category of the Duke Treadmill Score (p < 0.001). The authors concluded that CCR is feasible and effective for secondary prevention after transient ischemic attack or mild, non-disabling stroke, offering a promising model for vascular protection across chronic disease entities. The authors stated that they know of no similar previous investigation, and are now conducting a randomized trial.
Jeffares and colleagues (2021) stated that the CR model has potential as an approach to providing rehabilitation following stroke. These researchers provided evidence for the participation of stroke patients in cardiac/cardiovascular rehabilitation programs internationally, whether or not such programs offer a cognitive intervention as part of treatment, and the impact of rehabilitation on post-stroke cognitive function. A total of 5 electronic databases were searched from inception to May 1, 2019, namely: Medline, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Central Register of Controlled Trials, and the Web of Science. Eligible studies included both randomized and non-randomized studies of CR-type interventions that measured cognitive function in patients with transient ischemic attack (TIA) or stroke. Of 14,153 records reviewed, 9 studies that delivered CR-type interventions to stroke patients were finally included. Only 3 of these studies delivered cognitive rehabilitation as part of the intervention. Cardiac rehabilitation had no statistically significant effect on cognitive function in 5 RCTs (SMD = 0.28, 95 % CI: -0.16 to 0.73) or in 3 one-group pre-post studies (SMD = 0.15, 95 % CI: -0.03 to 0.33). The authors concluded that this review highlighted that there were very few studies of delivery of CR to stroke patients and that the inclusion of cognitive interventions was even less common, despite the high prevalence of post-stroke cognitive impairment. These investigators noted that the CR model has the potential to be expanded to include patients post-stroke given the commonality of secondary prevention needs, thereby becoming a cardiovascular rehabilitation model. Up to 50 % of patients experience cognitive impairment following stroke; suggesting that a post-stroke cardiovascular rehabilitation model should incorporate specific cognitive strategies for patients. This systematic review identified 3 cardiovascular rehabilitation programs which delivered cognitive rehabilitation as part of treatment; however, evidence for efficacy was weak.
Cardiac Rehabilitation Following Surgery to Correct Anomalous Coronary Artery
Lee et al (2016) examined physiological and clinical relevance of an anomalous right coronary artery originating from left sinus of Valsalva (right ACAOS) with inter-arterial course in adults. For physiological assessment, fractional flow reserve (FFR) during dobutamine challenge was measured in 37 consecutive adult patients with lone right ACAOS with inter-arterial course. At baseline, mean FFR was 0.91 ± 0.06, declining to 0.89 ± 0.06 upon dobutamine infusion (p < 0.001). Dobutamine stress FFR was significant (≤ 0.8) in 3 patients (8.1 %), 2 of whom were surgically treated. Following surgery, dobutamine stress FFR rose from 0.76 to 0.94 and 0.76 to 0.98. Re-modelling index (r = 0.583, p = 0.002), minimal lumen area (diastole: r = 0.580, p = 0.002; systole: r = 0.0618, p < 0.001) and per cent area stenosis (r = -0.550, p = 0.004), measured by intravascular ultrasound (IVUS), correlated with dobutamine stress FFR. To assess the clinical relevance, follow-up data of 119 patients with lone right ACAOS with inter-arterial course were analyzed retrospectively; 2 deaths occurred during a median follow-up period of 4 years, for a mortality rate of 0.34 per 100 person-year. No instances of MI were recorded and 1 patient did undergo surgical re-vascularization in the course follow-up. The authors concluded that most instances of lone right ACAOS with inter-arterial course discovered in adults were physiologically insignificant and ran benign clinical courses. Conservative management may thus suffice in this setting if no definitive signs of myocardial ischemia were evident.
Furthermore, recent consensus guidelines on anomalous coronary artery implantation (Brothers et al, 2017) discussed certain exercise restrictions following surgery, but did not address whether they need monitored CR.
Cardiac Rehabilitation for Individuals with an Implantable Cardioverter Defibrillator
Nielsen and colleagues (2019) stated that an effective way of preventing sudden cardiac death (SCD) is the use of an implantable cardioverter defibrillator (ICD). In spite of the potential mortality benefits of receiving an ICD device, psychological problems experienced by patients after receiving an ICD may negatively impact their health-related QOL, and lead to increased re-admission to hospital and healthcare needs, loss of productivity and employment earnings, and increased morbidity and mortality. Evidence from other heart conditions suggested that CR should consist of both exercise training and psycho-educational interventions; such rehabilitation may benefit patients with an ICD. Prior systematic reviews of CR have excluded participants with an ICD. These researchers carried out a systematic review to examine the evidence for the use of exercise-based intervention programs following implantation of an ICD. To assess the benefits and harms of exercise-based CR programs (exercise-based interventions alone or in combination with psycho-educational components) compared with control (group of no intervention, treatment as usual or another rehabilitation program with no physical exercise element) in adults with an ICD. These investigators searched CENTRAL, Medline, Embase and 4 other databases on August 30, 2018 and 3 trials registers on November 14, 2017. They also undertook reference checking, citation searching and contacted study authors for missing data. These researchers included RCTs if they examined exercise-based CR interventions compared with no intervention, treatment as usual or another rehabilitation program. Subjects were adults (aged 18 years or older), who had been treated with an ICD regardless of type or indication. Two review authors independently extracted data and assessed risk of bias. The primary outcomes were all-cause mortality, serious AEs and health-related QOL. The secondary outcomes were exercise capacity, anti-tachycardia pacing, shock, non-serious AEs, employment or loss of employment and costs and cost-effectiveness. Risk of systematic errors (bias) was assessed by evaluation of pre-defined bias risk domains. Clinical and statistical heterogeneity were assessed. Meta-analyses were undertaken using both fixed-effect and random-effects models. These investigators used the GRADE approach to assess the quality of evidence. They identified 8 trials published from 2004 to 2017 randomizing a total of 1,730 subjects, with mean intervention duration of 12 weeks. All 8 trials were judged to be at overall high risk of bias and effect estimates were reported at the end of the intervention with a follow-up range of 8 to 24 weeks; 7 trials reported all-cause mortality, but deaths only occurred in 1 trial with no evidence of a difference between exercise-based CR and control (RR 1.96, 95 % CI: 0.18 to 21.26; subjects = 196; trials = 1; quality of evidence: low). There was also no evidence of a difference in serious AEs between exercise-based CR and control (RR 1.05, 95 % CI: 0.77 to 1.44; subjects = 356; trials = 2; quality of evidence: low). Due to the variation in reporting of health-related QOL outcomes, it was not possible to pool data. However, the 5 trials reporting health-related QOL at the end of the intervention, each showed little or no evidence of a difference between exercise-based CR and control. For secondary outcomes, there was evidence of a higher pooled exercise capacity (peak VO2) at the end of the intervention (MD 0.91 ml/kg/min, 95 % CI: 0.60 to 1.21; subjects = 1,485; trials = 7; quality of evidence: very low) favoring exercise-based CR, albeit there was evidence of substantial statistical heterogeneity (I2 = 78 %). There was no evidence of a difference in the risk of requiring anti-tachycardia pacing (RR 1.26, 95 % CI: 0.84 to 1.90; subjects = 356; trials = 2; quality of evidence: moderate), appropriate shock (RR 0.56, 95 % CI: 0.20 to 1.58; subjects = 428; studies = 3; quality of evidence: low) or inappropriate shock (RR 0.60, 95 % CI: 0.10 to 3.51; subjects = 160; studies = 1; quality of evidence: moderate). The authors concluded that due to a lack of evidence, they were unable to definitively assess the impact of exercise-based CR on all-cause mortality, serious AEs and health-related QOL in adults with an ICD. However, these findings provided very low-quality evidence that patients following exercise-based CR experienced a higher exercise capacity compared with the no exercise control. These researchers stated that further high-quality randomized trials are needed in order to examine the impact of exercise-based CR in this population on all-cause mortality, serious AEs, health-related QOL, anti-tachycardia pacing and shock.
Following Open Surgical Aortic Valve Replacement and Transcatheter Aortic Valve Implant
Anayo and colleagues (2019) stated that exercise-based CR may be beneficial to patients following transcatheter aortic valve implantation (TAVI) and open surgical aortic valve replacement (SAVR). In a systematic review and meta-analysis, these researchers examined the safety, efficacy, and costs of exercise-based CR post-TAVI and post-SAVR. They searched numerous data-bases, including Embase, Central and Medline, up to October 2017. These investigators included RCTs and non-RCTs of exercise-based CR compared with no exercise control in TAVI or SAVR patients of greater than or equal to 18 years of age. Data extraction and risk of bias assessments were performed independently by 2 reviewers. Narrative synthesis and meta-analysis (where appropriate) were performed for all relevant outcomes, and a Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis was also performed. A total of 6 studies, all at low-risk of bias, were included: 3 RCTs and 3 non-RCTs (total of 27 TAVI, 99 SAVR and 129 mixed patients), with follow-up of 2 to 12 months. There was an increase in pooled exercise capacity (SMD: 0.41, 95 % CI: 0.11 to 0.70; moderate certainty evidence as assessed by GRADE), with exercise-based rehabilitation compared with control. Data on other outcomes including QOL and clinical events were limited. The authors concluded that exercise-based CR probably improved exercise capacity of post-TAVI and post-SAVR patients in the short-term. Moreover, these researchers stated that well-designed, multi-center, high-quality, fully powered RCTs of longer (greater than or equal to 12 months) follow-up are needed to definitely examine the effects of exercise-based CR in TAVI and SAVR patients. Such future studies should seek to collect patient relevant outcomes including hospitalization, health-related QOL, and mortality.
The authors stated that this study had several drawbacks. First, the number of included RCTs and non-RCTs was small with a lack of consistent reporting of outcomes across studies. Second, although all studies were based on aerobic exercise training, there was considerable variation in the nature of exercise-based rehabilitation programs across studies. Furthermore, there were some differences in the populations (some studies examined TAVI only, SAVR only and mixed populations). The comparator of all the studies was no structured exercise, but in the Jairath study, standard care might have included receiving guidelines for activity after discharge. Also, no study fully detailed what usual care was, and it was possible that this might differ between studies. These factors were likely to have contributed to the statistical heterogeneity observed in the review. Third, although sensitivity analysis was performed where statistical heterogeneity could not be determined by both I2 and the χ2 p value, the review did not consider sensitivity analysis for best or worse case scenarios, with regards to AEs. This could give a guide to the potential impact on these findings of not including participants with events due to poor description of drop-outs. Fourth, the certainty of evidence of the included studies for the outcomes measured ranged from very-low to high. This was largely influenced by risk of bias assessment and sample size. Overall, the sample sizes for most studies were low and the reporting bias in the studies made risk of bias assessment and therefore its impacts on these findings very difficult. In spite of these drawbacks, this review included up-to-date studies, and a meta-analysis was also carried out where necessary, increasing its robustness.
Takotsubo (Stress) Cardiomyopathy
Waller et la (2013) noted that sub-arachnoid hemorrhage (SAH) induced myocardial dysfunction (often labeled neurogenic stunned myocardium) encompasses a spectrum of clinical presentations ranging from an isolated elevation of cardiac enzymes to cardiogenic shock. These investigators described a case of Takotsubo (stress) cardiomyopathy in a patient following acute aneurysmal SAH that showed an "inverse" or reverse Takotsubo pattern on echocardiography. The patient was a 46-year old woman who presented with acute cardiogenic shock following acute SAH necessitating aggressive cardio-pulmonary support in the intensive care unit (ICU). Her admission echocardiogram showed a depressed left ventricular ejection fraction (LVEF) of 25 %. The basal 2/3 of the left ventricle (LV) was severely hypo-kinetic and the apical 1/3 of the LV was hyper-contractile, i.e., the reverse or inverse Takotsubo pattern of regional wall motion abnormality. With ongoing aggressive support her cardiovascular function steadily improved and on day 6 her follow-up echo showed LVEF increased to 60 to 65 % with resolution of the previous regional wall motion abnormality. The patient was discharged to a neuro-rehabilitation facility on day 16. The authors concluded that the "inverse" or "reverse" Takotsubo pattern of regional wall motion abnormalities, i.e., with preserved apical LV contractility and hypokinesis of the basal walls of the LV is more common in patients following acute SAH.
Wu et al (2019) examined participation rates and outcomes for patients with Takotsubo cardiomyopathy (TC) in a CR program. Patients at 2 academic medical centers with a discharge diagnosis of TC from January 2008 to March 2015 were retrospectively identified. Patients meeting the Mayo Clinic criteria for TC were cross-matched to the CR center affiliated with the hospitals to determine the referral rate and outcomes after completion of the program. A total of 380 patients were identified who survived the index hospitalization; 18 patients (5 %) were referred to CR, 15 enrolled, and of those enrolled, 10 patients (67 %) completed the program. Patients undergoing percutaneous coronary intervention (PCI) of a non-culprit vessel at the time of diagnosis was the only predictor for referral to CR (11 % versus 1 %, p = 0.01). The 10 patients who completed CR attended 33 ± 6 (range of 20 to 36) sessions. Weight and body mass index (BMI) reduction were 2.8 ± 3.5 lb and 0.6 ± 0.7 kg/m (p = 0.04, both), respectively. Post-CR exercise duration was 37 ± 4 mins/session, which improved by 13 ± 6 mins/session from baseline (p < 0.01); 2 patients entered the phase-III maintenance program; 1-year cardiac re-admission rates were comparable among patients who completed CR and those who were referred but did not attend or complete CR (0 % versus 13 %, p = 0.47). The authors concluded that referral for the TC population was low; however, enrollment and completion rates were adequate, with PCI in non-culprit vessel as the only predictor of CR referral. These researchers stated that limited data showed CR may help with weight reduction and improve exercise duration. It did not appear that CR had an effect on total mortality and other major clinical end-points.
Furthermore, an UpToDate review on “Management and prognosis of stress (takotsubo) cardiomyopathy” (Reeder and Prasad, 2020) does not mention cardiac rehabilitation as a management option.
Cardiac Rehabilitation After Closure of Patent Foramen Ovale
UpToDate reviews on “Treatment of patent foramen ovale (PFO) for secondary stroke prevention” (Messe and Brecker, 2021), and “Patent foramen ovale” (Hara, 2021) do not mention cardiac rehabilitation as a management tool.
Comprehensive Outpatient Cardiac Rehabilitation in Patients with Heart Failure
In a systematic review and meta-analysis, Gore et al (2023) examined the impact of comprehensive outpatient CR on exercise capacity, functional status, and QOL in patients with HF. PubMed, Embase, and CINAHL were searched using keywords and MeSH terms on heart failure and cardiac rehabilitation. Randomized clinical trials published in English using outpatient exercise-based CR in patients with HF were included. The GRADE analysis was employed for quality appraisal. Pooled estimates were computed using SMDs and 95 % CIs. Primary outcomes were functional status (6MWD, QOL, exercise capacity using peak oxygen consumption, muscle strength, and endurance). A total of 11 RCTs entailing 1,523 subjects ranging from 45 to 80 years of age; and an intervention duration ranging from 2 to 26 weeks were analyzed. Pooled results indicated significant improvements with comprehensive CR on 6MWD (SMD = 0.30; 95 % CI: 0.06 to 0.54) and oxygen consumption (SMD = 0.23; 95 % CI: 0.06 to 0.40). However, there was no additional benefit for the QOL beyond that observed in the comparison groups. The authors concluded that results of this study suggested that comprehensive outpatient CR was associated with significantly better clinical outcomes than single-component exercise programs in CR settings, multi-component exercise in non-CR settings, or no exercise.
Cardiac Rehabilitation Following Thoracic Aortic Repair
Koenders et al (2023) stated that it is important to gain more knowledge regarding the risks and benefits of exercise in patients recovering from thoracic aortic repair. In a systematic review and meta-analysis, these investigators examined changes in cardio-respiratory fitness, blood pressure (BP), and the incidence of AEs during CR in patients recovering from thoracic aortic repair. They carried out a systematic review and random-effects meta-analysis of outcomes before versus after outpatient CR in patients recovering from thoracic aortic repair. Medline, Embase, and CINAHL were systematically searched for eligible studies. Overall certainty of evidence was scored with GRADE. The authors included 5 studies with data from in total 241 patients. Data from 1 study could not be used in the meta-analysis because they were provided in a different unit of measure; the remaining 4 studies with data of 146 patients were included in the meta-analysis. The mean maximal work-load increased with 28.7 W (95 % CI: 21.8 W to 35.6 W, n = 146, low certainty of evidence). The mean systolic BP (SBP) during exercise testing increased with 25.4 mm Hg (95 % CI: 16.6 to 34.3, n = 133, low certainty of evidence). No exercise-induced AEs were reported. These outcomes showed that CR appeared to be safe and beneficial in improving exercise tolerance in patients recovering from thoracic aortic repair, although outcomes were based on data from a small, heterogeneous group of patients.
Postural Tachycardia Syndrome (POTS)
Shibata et al (2012) stated that recent studies have suggested the presence of cardiac atrophy as a key component of the pathogenesis of the postural orthostatic tachycardia syndrome (POTS), similar to physical deconditioning. It has also been shown that exercise intolerance is associated with a reduced stroke volume (SV) in POTS, and that the high heart rate observed at rest and during exercise in these patients is due to this low SV. These researchers tested the hypotheses that
- circulatory control during exercise is normal in POTS; and
- that physical “reconditioning” with exercise training improves exercise performance in patients with POTS.
A total of 19 (18 women) POTS patients completed a 3 month training program. Cardiovascular responses during maximal exercise testing were assessed in the upright position before and after training. Resting left ventricular diastolic function was evaluated by Doppler echocardiography. Results were compared with those of 10 well-matched healthy sedentary controls. A lower SV resulted in a higher heart rate in POTS at any given oxygen uptake (V(O(2))) during exercise while the cardiac output (Q(c))-V(O(2)) relationship was normal. V(O(2peak)) was lower in POTS than controls (26.1 ± 1.0 (SEM) versus 36.3 ± 0.9 ml kg-1 min-1; p < 0.001) due to a lower peak SV (65 ± 3 versus 80 ± 5 ml; p = 0.009). V(O(2peak)) increased by 11 % (p < 0.001) due to increased peak SV (p = 0.021) and was proportional to total blood volume. Peak heart rate was similar, but heart rate recovery from exercise was faster after training than before training (p = 0.036 for training and 0.009 for interaction). Resting diastolic function was mostly normal in POTS before training, though diastolic suction was impaired (p = 0.023). There were no changes in any Doppler index after training. The authors concluded that these results suggested that short-term exercise training improves physical fitness and cardiovascular responses during exercise in patients with POTS.
Benarroch (2012) noted that management of POTS includes avoidance of precipitating factors, volume expansion, physical counter-maneuvers, exercise training, pharmacotherapy (fludrocortisone, midodrine, beta-blockers, and/or pyridostigmine), and behavioral-cognitive therapy.
Although it can be argued that a structured exercise program for physical reconditioning may be beneficial for patients with POTS, it is unclear there is a need for a supervised cardiac rehabilitation program. Furthermore, an UpToDate review on “Postural tachycardia syndrome” (Freeman and Kaufman, 2014) does not mention cardiac rehabilitation as a management tool.
Pearce et al (2023) state that despite expert consensus suggesting exercise is recommended for patients with postural tachycardia syndrome (POTS), there are no randomized control trials examining this rigorously. Thus, the authors designed a study to co-create a feasibility trial protocol and a rehabilitation intervention for people living with POTS. The authors used the 'three co's framework' of co-define, co-design and co-refine. Recruitment included key national charities and National Health Service Trusts treating people living with POTS in the UK. Seven intervention practitioners were trained in the rehabilitation intervention, providing feedback for further co-refinement. The final co-created intervention comprises online physical activity, and lifestyle and behavior change support sessions. It is based on functional movement activities using a patient-centered approach tailored to individual needs. Physical activity intensity is guided by individuals' perception of effort rather than by objective measures. Recumbent bikes were provided for home use. Patients deemed randomization to be acceptable because research in this area was considered important. The authors concluded that an innovative approach was used to co-create the PostUraL tachycardia Syndrome Exercise (PULSE) intervention and feasibility trial protocol to meet the evidence-based and logistical needs of people living with POTS, clinicians, service deliverers, third-sector organizations, academics and funders. This can be used as a successful example and template for future research internationally. People living with POTS were recognized as experts and involved in every aspect of conceptualization, design and refinement. Per the authors, this complex rehabilitation intervention is currently being tested in a randomized feasibility trial comparing the PULSE intervention with best-practice usual care for people living with POTS. Research in POTS is currently limited and would benefit from the inclusion of a wider range of ethnicities, genders and cultures.
An UpToDate review on "Postural tachycardia syndrome” (Cheshire, 2023) does not specify “cardiac” rehab as a management option for POTS. The author states that supervised training may be needed for patients who cannot adhere to an exercise program on their own or believe exercise to be too difficult; however, the benefits of exercise in POTS have been demonstrated in small studies.
Online Cardiac Rehabilitation Program
Ozasa et al (2024) stated that comprehensive CR program is recommended for patients with CAD; however, many facilities do not have established programs for dietary guidance as well as patient education, resulting in an exercise-based CR program and limited effectiveness for secondary prevention. These researchers noted that a pilot study will be carried out to develop an online Japanese-style intensive CR (J-ICR) program for Japanese patients with CAD and will examine adherence, safety, and effectiveness. A total of 24 patients diagnosed with stable CAD will be randomly assigned in a 1 : 1 ratio to either an early or late-phase group. The program will comprise the following 4 parts: exercise sessions; dietary education centered on "the Japan diet"; mindfulness; and group support, with a frequency of 3 hours per session, once-weekly for 12 weeks (a total of 36 hours). The primary endpoint will be program feasibility, determined by examining its adherence. Physical examination and function, stress-coping skills, risk of classic CAD (e.g., lipid profile, glucose tolerance, and BP), as well as dietary changes will be evaluated as secondary endpoints. The authors concluded that the online J-ICR program is designed as a comprehensive CR program for Japanese patients with CAD. These investigators stated that If this program demonstrates high adherence and an improvement in CAD risk factors, its secondary prevention effect should be verified with appropriately powered randomized trials at multiple centers.
Patients on Chemotherapy
Diaz-Balboa et al (2021) noted that anthracyclines and monoclonal antibodies against human epidermal growth factor receptor-2 (HER2) are often used to treat breast cancer (BC); however, they are associated with risk of developing cardio-toxicity. Implementation of cardio-protective strategies as part of BC treatment are needed. To-date, a limited number of studies have examined the effectiveness of CR programs or exercise programs in the prevention of cardio-toxicity via an integral assessment of cardiac function. The ONCORE study proposed an exercise-based CR program as a non-pharmacological tool for the management of chemotherapy-induced cardio-toxicity. The study protocol described a prospective RCT aimed to examine if an intervention via an exercise-based CR program could effectively prevent cardio-toxicity induced by anthracyclines and/or anti-HER2 antibodies in women with BC. A total of 340 women with BC at early stages scheduled to receive cardio-toxic chemotherapy will be randomly assigned (1:1) to participation in an exercise-based CR program (intervention group) or to usual care and physical activity recommendation (control group). Primary outcomes include changes in LVEF and global longitudinal strain as markers of cardiac dysfunction assessed by TTE. Secondary outcomes comprise levels of cardiovascular biomarkers and cardiopulmonary function via peak oxygen uptake determination, physical performance and psychosocial status. Supervised exercise program-related outcomes including safety, adherence/compliance, expectations and physical exercise in- and out-of-hospital are studied as exploratory outcomes; TTE, clinical test as well as questionnaires will be carried out at the beginning and 2 weeks after completion of chemotherapy. The authors concluded that the growing incidence of BC and the risk of cardio-toxicity derived from cancer treatments demand adjuvant cardio-protective strategies. The proposed study may determine if an exercise-based CR program is effective in minimizing chemotherapy-induced cardio-toxicity in this population of women with early-stage BC. Recruitment for this clinical trial commenced in August 2018 and was expected to be completed by March 1, 2021, considering the withdrawal of 1 center from the study.
Kerrigan et al (2023) stated that HF due to cardio-toxicity is a leading non-cancer-related cause of morbidity and mortality in cancer survivors; CR improves cardio-respiratory fitness (CRF) and reduces morbidity and mortality in patients with HF. However, little is known regarding its effects on cardio-toxicity in the cancer population. In a RCT, these researchers examined if participation in CR would improve CRF in patients undergoing treatment with either doxorubicin or trastuzumab who exhibit markers of sub-clinical cardio-toxicity. Female patients with cancer (n = 28: BC, n = 1: leiomyosarcoma) and evidence of sub-clinical cardio-toxicity (i.e., greater than 10 % relative decrease in global longitudinal strain or a cardiac troponin of greater than 40 ng/L) were randomized to 10 weeks of CR or usual care. Exercise consisted of 3 day/week of interval training at 60 % to 90 % of heart rate (HR) reserve. CRF, as measured by peak oxygen uptake (V˙ o2peak ), improved in the CR group (16.9 + 5.0 to 18.5 + 6.0 ml/kg/min) while it decreased in the usual care group (17.9 + 3.9 to 16.9 + 4.0 ml/kg/min) (p = 0.009). No changes were observed between groups with respect to high-sensitivity troponin or global longitudinal strain. The authors concluded that the findings of this study suggested that the use of CR may be a viable option to attenuate the reduction in CRF that occurred in patients undergoing cardio-toxic chemotherapy. Moreover, these researchers stated that the long-term effects of exercise on chemotherapy-induced HF warrant further investigation.
Diaz-Balboa et al (2024) noted that BC treatment with anthracyclines and/or anti- HER2 antibodies is associated with an increased risk of cardiovascular disease complications, including cancer therapy-related cardiac dysfunction (CTRCD). While Cardio-Oncology Rehabilitation (CORe) programs including exercise have emerged to minimize these risks, its role in preventing CTRCD is unclear. In a RCT, these investigators examined the effectiveness of an exercise-based CORe program in preventing CTRCD ] -- LVEF drop of 10 % of more to a value of less than 53 % or a decrease of greater than 15 % in global longitudinal strain (GLS). Secondary outcomes examined changes in cardiac biomarkers, physical performance including peak oxygen consumption, psychometric and lifestyle outcomes. Safety, adherence, and patient satisfaction were also assessed. This study included 122 early-stage BC women receiving anthracyclines and/or anti-HER2 antibodies, randomized to CORe (n = 60) or usual care with exercise recommendation (n = 62). Comprehensive assessments were carried out at baseline and after cardio-toxic treatment completion. The average duration of the intervention was 5.8 months. No cases of CTRCD were identified during the study. LVEF decreased in both groups, but was significantly attenuated in the CORe group [-1.5 % (-2.9 to -0.1); p = 0.006], with no changes detected in GLS or cardiac biomarkers. The CORe intervention resulted in significant BMI reduction (p = 0.037), especially in obese patients [3.1 kg/m2 (1.3 to 4.8)]. Physical performance and QOL remained stable, while physical activity level increased in both groups; and no AEs were detected. The authors concluded that the findings of this study suggested that CORe programs were safe and may aid in attenuating LVEF decline in BC women receiving cardiotoxic therapy and reduce BMI in obese patients. Moreover, these researchers stated that further investigations are needed to validate and extend these findings to identify the most effective intervention and optimize its implementation.
The authors stated that this study had several drawbacks. First, no cases of CTRCD were detected according to the formal definition employed in the study design. Recent data have indicated a lower incidence of cardio-toxicity within the studied population than it was expected at the time of trial design. Consequently, although this trial could not prove the effectiveness of the exercise-based CORe program in preventing CTRCD as previously defined, it was worth highlighting that it enrolled the largest number of subjects in a CORe program to-date and provided encouraging data suggesting attenuation of LVEF decline. Second, there was a limitation in terms of long-term cardio-toxicity monitoring, as evidence indicated that CTRCD could manifest months or even years after the completion of treatment. Third, due to pandemic-related safety recommendations concerning COVID-19, some VO2peak measurements had to be estimated using the 6-min walk test (6MWT).
Appendix
New York Heart Association (NYHA) Functional Classification System - Designed to classify heart failure according to severity of symptoms:
- Class I (mild) - No limitations on physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath) or anginal pain
- Class II (mild) - Slight limitation of physical activity; comfortable at rest; ordinary physical activity results in fatigue, palpitation, dyspnea or anginal pain
- Class III (moderate) - Marked limitation of physical activity; comfortable at rest; less than ordinary activity causes fatigue, palpitation, dyspnea or anginal pain
- Class IV (severe) - Inability to carry on any physical activity without discomfort; symptoms of cardiac insufficiency may be present even at rest. If any physical activity is undertaken, discomfort increases.
References
The above policy is based on the following references:
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- Ades PA, Savage PD, Poehlman ET, et al. Lipid lowering in the cardiac rehabilitation setting. J Cardiopulm Rehabil. 1999;19(4):255-260.
- Ades PA. Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med. 2001;345(12):892-902.
- American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR). Guidelines for Cardiac Rehabilitation and Secondary Prevention Programs. 4th ed. Champaign, IL: Human Kinetics; 2004.
- American Association of Cardiovascular and Pulmonary Rehabilitation; American College of Cardiology Foundation; American Heart Association Task Force on Performance Measures (Writing Committee to Develop Clinical Performance Measures for Cardiac Rehabilitation), Thomas RJ, King M, Lui K, et al. AACVPR/ACCF/AHA 2010 Update: Performance Measures on Cardiac Rehabilitation for Referral to Cardiac Rehabilitation / Secondary Prevention Services Endorsed by the American College of Chest Physicians, the American College of Sports Medicine, the American Physical Therapy Association, the Canadian Association of Cardiac Rehabilitation, the Clinical Exercise Physiology Association, the European Association for Cardiovascular Prevention and Rehabilitation, the Inter-American Heart Foundation, the National Association of Clinical Nurse Specialists, the Preventive Cardiovascular Nurses Association, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2010;56(14):1159-1167.
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