Anderson Lindsey, Nguyen Tricia T, Dall Christian H, Burgess Laura, Bridges Charlene, Taylor Rod S
Institute of Health Research, University of Exeter Medical School, Veysey Building, Salmon Pool Lane, Exeter, UK, EX2 4SG.
Dept. of Cardiology, Dept. of Physical Therapy and IOC Sports Institute Copenhagen, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, Copenhagen, Denmark.
Cochrane Database Syst Rev. 2017 Apr 4;4(4):CD012264. doi: 10.1002/14651858.CD012264.pub2.
Heart transplantation is considered to be the gold standard treatment for selected patients with end-stage heart disease when medical therapy has been unable to halt progression of the underlying pathology. Evidence suggests that aerobic exercise training may be effective in reversing the pathophysiological consequences associated with cardiac denervation and prevent immunosuppression-induced adverse effects in heart transplant recipients.
To determine the effectiveness and safety of exercise-based rehabilitation on the mortality, hospital admissions, adverse events, exercise capacity, health-related quality of life, return to work and costs for people after heart transplantation.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO) and Web of Science Core Collection (Thomson Reuters) to June 2016. We also searched two clinical trials registers and handsearched the reference lists of included studies.
We included randomised controlled trials (RCTs) of parallel group, cross-over or cluster design, which compared exercise-based interventions with (i) no exercise control (ii) a different dose of exercise training (e.g. low- versus high-intensity exercise training); or (iii) an active intervention (i.e. education, psychological intervention). The study population comprised adults aged 18 years or over who had received a heart transplant.
Two review authors independently screened all identified references for inclusion based on pre-specified inclusion criteria. Disagreements were resolved by consensus or by involving a third person. Two review authors extracted outcome data from the included trials and assessed their risk of bias. One review author extracted study characteristics from included studies and a second author checked them against the trial report for accuracy.
We included 10 RCTs that involved a total of 300 participants whose mean age was 54.4 years. Women accounted for fewer than 25% of all study participants. Nine trials which randomised 284 participants to receive exercise-based rehabilitation (151 participants) or no exercise (133 participants) were included in the main analysis. One cross-over RCT compared high-intensity interval training with continued moderate-intensity training in 16 participants. We reported findings for all trials at their longest follow-up (median 12 weeks).Exercise-based cardiac rehabilitation increased exercise capacity (VO) compared with no exercise control (MD 2.49 mL/kg/min, 95% CI 1.63 to 3.36; N = 284; studies = 9; moderate quality evidence). There was evidence from one trial that high-intensity interval exercise training was more effective in improving exercise capacity than continuous moderate-intensity exercise (MD 2.30 mL/kg/min, 95% CI 0.59 to 4.01; N = 16; 1 study). Four studies reported health-related quality of life (HRQoL) measured using SF-36, Profile of Quality of Life in the Chronically Ill (PLC) and the World Health Organization Quality Of Life (WHOQoL) - BREF. Due to the variation in HRQoL outcomes and methods of reporting we were unable to meta-analyse results across studies, but there was no evidence of a difference between exercise-based cardiac rehabilitation and control in 18 of 21 HRQoL domains reported, or between high and moderate intensity exercise in any of the 10 HRQoL domains reported. One adverse event was reported by one study.Exercise-based cardiac rehabilitation improves exercise capacity, but exercise was found to have no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients whose health is stable.There was no evidence of statistical heterogeneity across trials for exercise capacity and no evidence of small study bias. The overall risk of bias in included studies was judged as low or unclear; more than 50% of included studies were assessed at unclear risk of bias with respect to allocation concealment, blinding of outcome assessors and declaration of conflicts of interest. Evidence quality was assessed as moderate according to GRADE criteria.
AUTHORS' CONCLUSIONS: We found moderate quality evidence suggesting that exercise-based cardiac rehabilitation improves exercise capacity, and that exercise has no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients. Cardiac rehabilitation appears to be safe in this population, but long-term follow-up data are incomplete and further good quality and adequately-powered trials are needed to demonstrate the longer-term benefits of exercise on safety and impact on both clinical and patient-related outcomes, such as health-related quality of life, and healthcare costs.
对于经药物治疗无法阻止潜在病情进展的特定终末期心脏病患者，心脏移植被视为金标准治疗方法。有证据表明，有氧运动训练可能有效逆转与心脏去神经支配相关的病理生理后果，并预防心脏移植受者免疫抑制引起的不良反应。
确定基于运动的康复对心脏移植后患者的死亡率、住院率、不良事件、运动能力、健康相关生活质量、重返工作岗位情况及费用的有效性和安全性。
我们检索了截至2016年6月的Cochrane图书馆中的Cochrane对照试验中心注册库（CENTRAL）、MEDLINE（Ovid）、Embase（Ovid）、CINAHL（EBSCO）和科学引文索引核心合集（汤森路透）。我们还检索了两个临床试验注册库，并手工检索了纳入研究的参考文献列表。
我们纳入了平行组、交叉或整群设计的随机对照试验（RCT），这些试验将基于运动的干预措施与以下情况进行比较：（i）无运动对照；（ii）不同剂量的运动训练（例如低强度与高强度运动训练）；或（iii）积极干预（即教育、心理干预）。研究人群包括18岁及以上接受心脏移植的成年人。
两位综述作者根据预先指定的纳入标准独立筛选所有识别出的参考文献以确定是否纳入。分歧通过协商一致或由第三人参与解决。两位综述作者从纳入的试验中提取结局数据并评估其偏倚风险。一位综述作者从纳入研究中提取研究特征，另一位作者对照试验报告检查其准确性。
我们纳入了10项RCT，共涉及300名参与者，平均年龄为54.4岁。女性占所有研究参与者的比例不到25%。主要分析纳入了9项试验，将284名参与者随机分为接受基于运动康复组（151名参与者）或无运动组（133名参与者）。一项交叉RCT比较了16名参与者的高强度间歇训练与持续中等强度训练。我们在所有试验最长随访期（中位数12周）报告了研究结果。与无运动对照相比，基于运动的心脏康复提高了运动能力（VO）（MD 2.49 mL/kg/min，95%CI 1.63至3.36；N = 284；研究 = 9；中等质量证据）。一项试验有证据表明，高强度间歇运动训练在提高运动能力方面比持续中等强度运动更有效（MD 2.30 mL/kg/min，95%CI 0.59至4.01；N = 16；1项研究）。四项研究报告了使用SF - 36、慢性病生活质量概况（PLC）和世界卫生组织生活质量（WHOQoL） - BREF测量的健康相关生活质量（HRQoL）。由于HRQoL结局和报告方法的差异，我们无法对各研究结果进行Meta分析，但在报告的21个HRQoL领域中的18个领域，基于运动的心脏康复与对照之间没有差异的证据，在报告的10个HRQoL领域中的任何一个领域，高强度与中等强度运动之间也没有差异的证据。一项研究报告了1例不良事件。在健康状况稳定的心脏移植受者中，基于运动的心脏康复提高了运动能力，但运动在短期（中位数12周随访）对健康相关生活质量没有影响。在运动能力方面，各试验之间没有统计学异质性的证据，也没有小研究偏倚的证据。纳入研究的总体偏倚风险被判定为低或不明确；超过50%的纳入研究在分配隐藏、结局评估者盲法和利益冲突声明方面被评估为偏倚风险不明确。根据GRADE标准，证据质量被评估为中等。
我们发现中等质量证据表明，在心脏移植受者中，基于运动的心脏康复提高了运动能力，且运动在短期（中位数12周随访）对健康相关生活质量没有影响。心脏康复在该人群中似乎是安全的，但长期随访数据不完整，需要进一步高质量且有足够样本量的试验来证明运动对安全性的长期益处以及对临床和患者相关结局（如健康相关生活质量和医疗费用）的影响。
