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Scientific Review

Exercise Interventions in Patients With Implantable Cardioverter-Defibrillators and Cardiac Resynchronization Therapy


Steinhaus, Daniel A. MD; Lubitz, Steven A. MD, MPH; Noseworthy, Peter A. MD; Kramer, Daniel B. MD, MPH

Author Information
Journal of Cardiopulmonary Rehabilitation and Prevention: September 2019 - Volume 39 - Issue 5 - p 308-317
doi: 10.1097/HCR.0000000000000389

Implantable cardioverter-defibrillators (ICDs) including those with cardiac resynchronization therapy capability (CRT-Ds) are recommended for selected patients at risk for ventricular arrhythmias.1,2 Approximately 80% of patients receive devices for primary prevention, usually based on a history of systolic heart failure despite optimal medical therapy, while the remainder includes survivors of sudden cardiac arrest.3,4 In the United States, approximately 100 000 ICDs are implanted annually, and >1 million patients are living with these devices.5

For patients with cardiovascular disease including heart failure and coronary artery disease, aerobic exercise provides significant benefits with improvement in exercise capacity and quality of life.6,7 However, despite guidelines recommending exercise training, there is significant underutilization of this important therapy.8 Patients with ICDs introduce several concerns regarding exercise, including increased burden of ventricular arrhythmias, ICD shocks, and sudden death. In some cases, physical activity can precipitate ventricular arrhythmias or supraventricular arrhythmias that result in ICD therapy.9 The risk for cardiovascular complications during exercise testing and training may be higher in patients with a history of life-threatening arrhythmias or cardiac arrest.10 However, regular exercise, such as cardiac rehabilitation, may exert a protective effect for patients whose cardiac substrate supports indications for ICDs and CRT-Ds.11,12 Accordingly, we performed a systematic review and meta-analysis of trial-level data with the purpose of evaluating exercise interventions in patients with ICDs and CRT-Ds to characterize study design, safety, and effectiveness of exercise in affected patients.



A protocol for the systematic review was developed prospectively and registered with the International Prospective Register of Systematic Reviews (PROSPERO) at, registration number CRD42015027422. Following PRISMA guidelines13 for systematic reviews, we performed a systematic literature search of the MEDLINE/PubMed, Google Scholar, EMBASE, and Cochrane Library databases for articles using the following terms: “implantable cardioverter-defibrillators”; “ICDs”; “cardiac resynchronization therapy”; “CRT”; and any one of the following: “activity”; “exercise”; “training”; or “rehabilitation.” We limited dates to January 1, 2000 to October 1, 2015, to evaluate contemporary practice. No language requirement was placed on the search.

After the initial sample was obtained, we evaluated study titles and abstracts to identify potentially relevant studies and then obtained the full-text articles to confirm which studies would be included in the systematic review. When the literature search was complete, we engaged in manual reference mining of our sample of articles.


Prespecified inclusion criteria involved characteristics of the studies themselves and the data presented. Studies included must have reported empirical data regarding an intervention or program targeting physical activity, rehabilitation programs, or exercise training specifically intended for patients with ICDs. Both clinical trials and observational studies were eligible for inclusion. Case studies, editorials, opinion pieces, commentaries, and reviews or meta-analyses without original data or analysis were excluded. We excluded trials that examined device-guided exercise optimization (eg, atrial-ventricular delay optimization during exercise) or studies that evaluated exercise capacity without a cardiovascular training component.


Two authors (D.A.S. and D.B.K.) independently reviewed the initial list of eligible studies, with any disagreements resolved with consultation among all 4 authors. We noted the methodology and results, with a focus on the sample size, intervention, and assessment of endpoints. Then the major limitations of each study were formally assessed. Possible sources of bias in the included studies were noted, including funding sources and methodological limitations (including lack of detail reporting of methods). Qualitative analysis was then performed on these studies to evaluate the type and duration of exercise intervention, type of primary and secondary endpoints, and outcomes. Data were evaluated at a trial level.

The primary quantitative outcome for this review is ICD shock during follow-up. This outcome was assessed in all studies that reported the outcome in both the intervention and control arm as well as in the subset of studies with a randomized controlled trial (RCT) design. Implantable cardioverter-defibrillator shock was categorized as a dichotomous variable and evaluated in a standard 2 × 2 table with Fisher exact test using STATA version 12.1 software (StataCorp). Odds ratio and 95% CI were generated from these analyses. Change in peak

O2 was analyzed in all studies that reported the outcome and evaluated with the t test statistic. A sensitivity analysis was performed.



The primary literature search yielded 649 studies (Figure 1). After evaluating study titles, 75 study abstracts were screened. Of these, 25 full-text articles were assessed for eligibility. We excluded 9 studies that did not meet our primary entry criteria (ie, focus was not rehabilitation program or did not provide description of intervention). Of the remaining 16 studies, 8 were RCTs, 5 were single-arm studies, 2 were observational cohort trials, and 1 was a randomized crossover trial. These 16 studies were included for qualitative analysis. For quantitative analysis, 9 of these 16 studies were excluded as they did not report patient-level ICD shock data. Of the remaining 7 studies, 5 were RCTs and 2 were observational cohort studies. Table 1 describes the trial design, study locations, intervention, patient population, primary and secondary endpoints, primary and secondary outcomes, and funding sponsor.

Figure 1
Figure 1:
PRISMA flow diagram of study selection process. ICD indicates implantable cardioverter-defibrillator; RCT, randomized controlled trial.
Table 1
Table 1:
Design and Interventions of Included Studies


A total of 2547 patients (median sample size = 52, range: 24-1053) were included, with 1215 patients receiving exercise interventions and 1332 control patients. Patients predominately had New York Heart Association class II and class III heart failure. The mean ages of the patients in the studies ranged from 52 to 69 yr (median: 60 yr), a high percentage were males (82.7%), and mean left ventricular ejection fractions ranged from 24% to 43% (median: 33%).


Exercise interventions varied widely in character (Table 1). Studies included both inpatient and outpatient training with varied methods including aerobic exercise (walking, running, cycling, rowing, arm ergometry, calisthenics, and Nordic walking), strength training, stretching, and psychoeducational counseling including cognitive behavioral therapy. Home telemonitoring was also used in several studies. Exercise programs generally consisted of several weekly sessions (predominately 3 times/wk) for 25 to 90 min/session, offered over several weeks. Most studies also described methods of avoiding ICD interventions that generally included targeting a maximal heart rate during exercise of 10 to 30 beats/min lower than the ICD therapy rate threshold, or alternatively, adjusting the ICD therapy rate to be higher than the maximal achieved heart rate during exercise. Of note, in the largest trial,23 the patients were excluded if the ICD tachycardia detection limit was set below the target heart rate for exercise training (determined by 70% of heart rate reserve [peak heart rate during exercise testing minus resting heart rate times a percent]). The median duration of exercise intervention was 84 d (range of 23-168 d) and the median total follow-up was 109 d (range: 23 d to 48 mo).


Exercise performance measures were the most common primary endpoint (87.5%), with a majority of studies reporting

O2 peak (75%) (Table 2). Other primary outcome measures included median intensity of exercise in metabolic equivalents as estimated from patient-reported activity and frequency (12.5%), improvement in exercise test time during treadmill exercise testing (6.25%), functional class (12.5%), quality-of-life measures (6.3%), and ICD shocks (12.5%). The primary endpoint was found to be statistically significantly improved in the majority of studies (81%). Most studies reported ICD shocks and/or antitachycardia pacing (ATP) during exercise intervention (81%). In these studies, ICD interventions were uncommon during exercise, with 6 ICD shocks and 2 ATP events in 635 patients. Only 1 ICD shock was described as inappropriate (not further described) and all other shocks and ATP were appropriate for ventricular tachycardia.

Table 2
Table 2:
Primary and Secondary Outcomes of Included Studies

Cochrane risk of bias assessment tool was used to evaluate the quality of publications (see Supplemental Digital Content 1, available at: Among the RCTs, 2 studies reported random sequence generation while 2 other studies reported blinding of outcome assessment. There was no selective or incomplete reporting. There was no significant other bias noted in the studies.


A total of 7 studies reported the burden of ICD shocks during follow-up in both an intervention and control arm18,19,23,26–29 (Table 3). From these studies, ICD shocks were less common in patients receiving any exercise intervention (15.6% vs 23%, OR: 0.68; 95% CI, 0.48-0.80, P < .001, Figure 2). Among this group, 5 RCTs were included for evaluation of ICD shock rates.19,23,26–28 During the follow-up period of RCT trials, the patients receiving exercise interventions had a lower rate of ICD shocks (15.2% vs 20.1%, OR: 0.70; 95% CI, 0.53-0.92, P = .013, Figure 3). The rate of ATP was not consistently reported and was therefore not included in the quantitative analysis.

Table 3
Table 3:
Frequency of ICD Shocks by Study
Figure 2
Figure 2:
Frequency of shocks in all trials reporting shock outcomes.
Figure 3
Figure 3:
Frequency of shocks in randomized controlled trials reporting shock outcomes.

Change in

O2 peak with exercise intervention compared with control (usual care) was reported in 7 studies.

O2 peak improved significantly in patients receiving exercise intervention (1.98 vs 0.36 mL/kg/min, P < .001). Within this group, 6 studies were RCTs and demonstrated significant improvement in

O2 peak with exercise intervention (2.15 vs 0.54 mL/kg/min, P < .001).

Since data from Piccini et al23 provided a significant proportion of patients, sensitivity analysis was performed excluding these data. After this exclusion, there were no significant changes in the aforementioned outcomes.


This systematic review and meta-analysis found that exercise training appears to be safe and effective for patients with ICDs and CRT-Ds. A significant strength of this review is the wide search criteria and large number of articles screened for inclusion. Exercise interventions in the evaluated studies varied widely but all included regular cardiovascular activity, with a reassuring safety profile specifically regarding ICD shocks. While the primary endpoint definition varied, most studies found improvements using objective measurements such as peak

O2. Taken together, these findings support broader application of exercise training among patients with ICDs, though standardization of protocols is necessary for more rigorous future study.

These conclusions extend prior reviews in this area. A review by Isaksen et al30 identified 9 studies of exercise training in a total of 1889 patients with ICDs. They report a low burden of ICD therapies during exercise training as well as an improvement in aerobic fitness with exercise training. One limitation of this review was that the results from the large HF-ACTION trial23 had not yet been published. The more recent analysis from Pandey et al31 included the HF-ACTION trial results and evaluated a total of 6 trials (5 RCT, 1 non-RCT). They found that exercise training in patients with heart failure and ICDs improved cardiorespiratory fitness and was associated with a lower likelihood of ICD shocks. While both trials had similar findings to our study, our current review provides a more comprehensive evaluation of the available literature by assessing all available trials, including parallel-arm and single-arm studies.

Although fear of ICD therapies is a natural concern in this patient population, our review illustrates that, with appropriate programming and patient monitoring, ICD discharges were extremely rare both during exercise activity and in follow-up in the entire cohort. In fact, patients receiving an exercise intervention had fewer device shocks compared with those who did not engage in an exercise program. Exercise training may decrease both appropriate and inappropriate shocks by modifying autonomic tone with subsequent reductions in ventricular arrhythmia, sinus tachycardia, rapid atrial fibrillation, and other supraventricular tachycardias. While catecholamine levels are higher during exercise, chronic exercise blunts this effect.32,33 Exercise also increases resting parasympathetic tone that protects against ventricular arrhythmias 34,35 and sudden death.36 Furthermore, guidelines for ICD programming have also advanced significantly in recent years, which should reduce the likelihood of both inappropriate therapies and appropriate shocks for self-limited arrhythmia during exercise programs.

Importantly, exercise interventions that improve exercise capacity and decrease ICD shock burden can have significant benefits for patient quality of life. Patients receiving ICD shocks have been shown to have significant decrease in mental health and physical functioning.37 Implantable cardioverter-defibrillator shocks are associated with decreased physical activity,38 as well as increased anxiety and depression.39 Furthermore, a decrease in ICD shocks and ventricular arrhythmias may reduce myocardial and cerebral ischemia by limiting exposure to hypotensive events.40–43 There are several potential benefits of exercise training following ICD or CRT-D implantation including familiarization with the device, instruction about physical activity, psychological support, and improvement in exercise capacity.8

Consensus documents suggest that patients perform a symptom-limited cardiopulmonary exercise stress test or similar evaluation (eg, conventional exercise test or 6-min walk test) prior to initiation of an exercise training program.8,44 Pre-exercise testing allows for evaluation of the chronotropic response to exercise, effectiveness of medications, and the risk of reaching a heart rate in the ICD intervention zone. We recognize that formal exercise testing before initiating an exercise program may not always be practical, given resource and time constraints, and we would emphasize that providers should be aware of a patient's programmed ICD intervention zone to provide a safe exercise prescription. The American Heart Association statement suggests that the exercise prescription for patients with defibrillators should be limited to a maximal heart rate that is at least 10 to 15 beats/min lower than the intervention zone for the defibrillator. Heart rate monitoring during the exercise program can help avoid any inappropriate interventions.

Our analysis includes several potential limitations. First, study design varied greatly and made direct comparison difficult, with limited options for quantitative analysis. The large number of observational and nonrandomized studies provided an overall relatively low-quality of included studies. Confounding by indication, where healthier individuals would be more likely to be enrolled in exercise programs, in the observational studies may overestimate the benefits of exercise training and underestimate the risks of device shocks. In addition, selection bias may be present as only published studies were able to be included, though lack of consistent endpoint definition made formal analysis of publication bias difficult.

In conclusion, exercise training in patients with ICDs and CRT appears safe and effective based on our review of the relatively scant available literature. However, lack of consensus on design and endpoints limits broader application in this important patient population.


Dr Lubitz is supported by NIH grants K23HL114724 and a Doris Duke Charitable Foundation Clinical Scientist Development Award #2014105. Dr Noseworthy is supported by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery. Dr Kramer is supported by a Paul Beeson Career Development Award (NIH-NIA K23AG049563) and the Greenwall Faculty Scholars Program in Bioethics.


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exercise; implantable cardioverter defibrillator; meta-analysis; review

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