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Association Between Early Cardiac Rehabilitation and Long-term Survival in Cardiac Transplant Recipients



      To determine whether participation in early cardiac rehabilitation (CR) after heart transplant (HTx) affects long-term survival.

      Patients and Methods

      A retrospective review was conducted in 201 patients who underwent HTx at Mayo Clinic between June 1, 2000, and July 31, 2013. Patients were excluded with multiorgan transplant, no CR data, and follow-up less than 90 days after HTx. Demographic and exercise data at baseline before HTx were collected. Post-HTx exercise capacity, biopsy, CR data, and medications were collected at 1 through 5 and 10 years.


      Overall survival at 1, 5, and 10 years was 98%, 88%, and 82%, respectively; 29 patients died. Number of CR sessions attended in the first 90 days after HTx predicted survival in multivariate regression, controlling for baseline post-HTx 6-minute walk test (6MWT) results and rejection episodes (hazard ratio, 0.90; 95% CI, 0.82-0.97; P=.007). Additional univariate predictors of survival included pre-HTx 6MWT results, weight at HTx, and body mass index and systolic blood pressure at CR enrollment. Pre-HTx 6MWT results, body mass index, and post-HTx were associated with improvement in peak oxygen consumption.


      This report demonstrates, for the first time, an association between CR and long-term survival in patients after HTx. Further work should clarify the most beneficial aspects of CR.

      Abbreviations and Acronyms:

      ACEi (angiotensin-converting enzyme inhibitor), Aldo blocker (aldosterone antagonist), ARB (angiotensin receptor blocker), AZA (azathioprine), BMI (body mass index), BP (blood pressure), CCB (calcium channel blocker), CR (cardiac rehabilitation), ENaC (epithelial sodium channel inhibitor), HF (heart failure), HR (hazard ratio), HTx (heart transplant), LVEF (left ventricular ejection fraction), MCS (mechanical circulatory support), MMF (mycophenolate mofetil), QoL (quality of life), UNOS (United Network for Organ Sharing), VO2 (oxygen consumption), 6MWT (6-minute walk test)
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        • Lund L.H.
        • Edwards L.B.
        • Kucheryavaya A.Y.
        • et al.
        The Registry of the International Society for Heart and Lung Transplantation: Thirtieth Official Adult Heart Transplant Report–2013; focus theme: age.
        J Heart Lung Transplant. 2013; 32: 951-964
        • Hunt S.A.
        • Haddad F.
        The changing face of heart transplantation.
        J Am Coll Cardiol. 2008; 52: 587-598
        • Kugler C.
        • Gottlieb J.
        • Warnecke G.
        • et al.
        Health-related quality of life after solid organ transplantation: a prospective, multiorgan cohort study.
        Transplantation. 2013; 96: 316-323
        • Hummel M.
        • Michauk I.
        • Hetzer R.
        • Fuhrmann B.
        Quality of life after heart and heart-lung transplantation.
        Transplant Proc. 2001; 33: 3546-3548
        • Kavanagh T.
        Physical training in heart transplant recipients.
        J Cardiovasc Risk. 1996; 3: 154-159
        • Squires R.W.
        Exercise therapy for cardiac transplant recipients.
        Prog Cardiovasc Dis. 2011; 53: 429-436
        • Haykowsky M.
        • Taylor D.
        • Kim D.
        • Tymchak W.
        Exercise training improves aerobic capacity and skeletal muscle function in heart transplant recipients.
        Am J Transplant. 2009; 9: 734-739
        • Kobashigawa J.A.
        • Leaf D.A.
        • Lee N.
        • et al.
        Review of a controlled trial of exercise rehabilitation after heart transplantation.
        N Engl J Med. 1999; 340: 272-277
        • Bernardi L.
        • Radaelli A.
        • Passino C.
        • et al.
        Effects of physical training on cardiovascular control after heart transplantation.
        Int J Cardiol. 2007; 118: 356-362
        • Braith R.W.
        • Mills R.M.
        • Welsch M.A.
        • Keller J.W.
        • Pollock M.L.
        Resistance exercise training restores bone mineral density in heart transplant recipients.
        J Am Coll Cardiol. 1996; 28: 1471-1477
        • Deliva R.D.
        • Hassall A.
        • Manlhiot C.
        • Solomon M.
        • McCrindle B.W.
        • Dipchand A.I.
        Effects of an acute, outpatient physiotherapy exercise program following pediatric heart or lung transplantation.
        Pediatr Transplant. 2012; 16: 879-886
        • Kavanagh T.
        • Yacoub M.H.
        • Mertens D.J.
        • Kennedy J.
        • Campbell R.B.
        • Sawyer P.
        Cardiorespiratory responses to exercise training after orthotopic cardiac transplantation.
        Circulation. 1988; 77: 162-171
        • Niset G.
        • Coustry-Degre C.
        • Degre S.
        Psychosocial and physical rehabilitation after heart transplantation: 1-year follow-up.
        Cardiology. 1988; 75: 311-317
        • Keteyian S.
        • Shepard R.
        • Fedel E.
        • Rhoads G.
        • Levin T.
        Cardiovascular responses of heart transplant patients to exercise training.
        J Appl Physiol (1985). 1991; 70: 2627-2631
        • Zhao Q.M.
        • Mettauer B.
        • Epailly E.
        • et al.
        Effect of exercise training on leukocyte subpopulations and clinical course in cardiac transplant patients.
        Transplant Proc. 1998; 30: 172-175
        • Williams M.A.
        • Ades P.A.
        • Hamm L.F.
        • et al.
        Clinical evidence for a health benefit from cardiac rehabilitation: an update.
        Am Heart J. 2006; 152: 835-841
        • Balady G.J.
        • Ades P.A.
        • Bittner V.A.
        • et al.
        Referral, enrollment, and delivery of cardiac rehabilitation/secondary prevention programs at clinical centers and beyond: a presidential advisory from the American Heart Association.
        Circulation. 2011; 124: 2951-2960
        • Suaya J.A.
        • Shepard D.S.
        • Normand S.L.
        • Ades P.A.
        • Prottas J.
        • Stason W.B.
        Use of cardiac rehabilitation by Medicare beneficiaries after myocardial infarction or coronary bypass surgery.
        Circulation. 2007; 116: 1653-1662
        • Lavie C.J.
        • Cahalin L.P.
        • Chase P.
        • et al.
        Impact of cardiorespiratory fitness on the obesity paradox in patients with heart failure.
        Mayo Clin Proc. 2013; 88: 251-258
        • Marconi C.
        • Marzorati M.
        Exercise after heart transplantation.
        Eur J Appl Physiol. 2003; 90: 250-259
        • Shah N.D.
        • Dunlay S.M.
        • Ting H.H.
        • et al.
        Long-term medication adherence after myocardial infarction: experience of a community.
        Am J Med. 2009; 122: 961.e7-961.e13
        • Hsu C.-J.
        • Chen S.-Y.
        • Su S.
        • et al.
        The effect of early cardiac rehabilitation on health-related quality of life among heart transplant recipients and patients with coronary artery bypass graft surgery.
        Transplant Proc. 2011; 43: 2714-2717
        • Tegtbur U.
        • Busse M.W.
        • Jung K.
        • Pethig K.
        • Haverich A.
        Time course of physical reconditioning during exercise rehabilitation late after heart transplantation.
        J Heart Lung Transplant. 2005; 24: 270-274
        • Farmer S.A.
        • Grady K.L.
        • Wang E.
        • McGee E.C.
        • Cotts W.G.
        • McCarthy P.M.
        Demographic, psychosocial, and behavioral factors associated with survival after heart transplantation.
        Ann Thorac Surg. 2013; 95: 876-883
        • Kerrigan D.J.
        • Williams C.T.
        • Ehrman J.K.
        • et al.
        Cardiac rehabilitation improves functional capacity and patient-reported health status in patients with continuous-flow left ventricular assist devices: the Rehab-VAD Randomized Controlled Trial.
        JACC Heart Fail. 2014; 2: 653-659
        • Hayes K.
        • Leet A.S.
        • Bradley S.J.
        • Holland A.E.
        Effects of exercise training on exercise capacity and quality of life in patients with a left ventricular assist device: a preliminary randomized controlled trial.
        J Heart Lung Transplant. 2012; 31: 729-734
        • Flynn K.E.
        • Pin I.L.
        • Whellan D.J.
        • et al.
        Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial.
        JAMA. 2009; 301: 1451-1459
        • Swank A.M.
        • Horton J.
        • Fleg J.L.
        • et al.
        Modest increase in peak VO2 is related to better clinical outcomes in chronic heart failure patients: results from heart failure and a controlled trial to investigate outcomes of exercise training.
        Circ Heart Fail. 2012; 5: 579-585
        • Tabet J.-Y.
        • Meurin P.
        • Beauvais F.
        • et al.
        Absence of exercise capacity improvement after exercise training program: a strong prognostic factor in patients with chronic heart failure.
        Circ Heart Fail. 2008; 1: 220-226
        • Scrutinio D.
        • Passantino A.
        • Catanzaro R.
        • et al.
        Inpatient cardiac rehabilitation soon after hospitalization for acute decompensated heart failure: a propensity score study.
        J Cardiopulm Rehabil Prev. 2012; 32: 71-77
        • Menezes A.R.
        • Lavie C.J.
        • Milani R.V.
        • Forman D.E.
        • King M.
        • Williams M.A.
        Cardiac rehabilitation in the United States.
        Prog Cardiovasc Dis. 2014; 56: 522-529
        • Grace S.L.
        • Bennett S.
        • Ardern C.I.
        • Clark A.M.
        Cardiac rehabilitation series: Canada.
        Prog Cardiovasc Dis. 2014; 56: 530-535
        • Forman D.E.
        • Sanderson B.K.
        • Josephson R.A.
        • Raikhelkar J.
        • Bittner V.
        American College of Cardiology's Prevention of Cardiovascular Disease Section. Heart failure as a newly approved diagnosis for cardiac rehabilitation: challenges and opportunities.
        J Am Coll Cardiol. 2015; 65: 2652-2659
        • Pack Q.R.
        • Goel K.
        • Lahr B.D.
        • et al.
        Participation in cardiac rehabilitation and survival after coronary artery bypass graft surgery: a community-based study.
        Circulation. 2013; 128: 590-597
        • Goel K.
        • Pack Q.R.
        • Lahr B.
        • et al.
        Cardiac rehabilitation is associated with reduced long-term mortality in patients undergoing combined heart valve and CABG surgery.
        Eur J Prev Cardiol. 2015; 22: 159-168
        • Dunlay S.M.
        • Pack Q.R.
        • Thomas R.J.
        • Killian J.M.
        • Roger V.L.
        Participation in cardiac rehabilitation, readmissions, and death after acute myocardial infarction.
        Am J Med. 2014; 127: 538-546
        • Goel K.
        • Lennon R.J.
        • Tilbury R.T.
        • Squires R.W.
        • Thomas R.J.
        Impact of cardiac rehabilitation on mortality and cardiovascular events after percutaneous coronary intervention in the community.
        Circulation. 2011; 123: 2344-2352
        • Lavie C.J.
        • Alpert M.A.
        • Arena R.
        • Mehra M.R.
        • Milani R.V.
        • Ventura H.O.
        Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure.
        JACC Heart Fail. 2013; 1: 93-102
        • McAuley P.A.
        • Artero E.G.
        • Sui X.
        • et al.
        The obesity paradox, cardiorespiratory fitness, and coronary heart disease.
        Mayo Clin Proc. 2012; 87: 443-451
        • Taylor D.O.
        • Stehlik J.
        • Edwards L.B.
        • et al.
        Registry of the International Society for Heart and Lung Transplantation: Twenty-sixth Official Adult Heart Transplant Report-2009.
        J Heart Lung Transplant. 2009; 28: 1007-1022
        • Casanova C.
        • Cote C.G.
        • Marin J.M.
        • et al.
        The 6-min walking distance: long-term follow up in patients with COPD.
        Eur Respir J. 2007; 29: 535-540
        • Kundu A.
        • Maji A.
        • Sarkar S.
        • Saha K.
        • Jash D.
        • Maikap M.
        Correlation of six minute walk test with spirometric indices in chronic obstructive pulmonary disease patients: a tertiary care hospital experience.
        J Assoc Chest Physicians. 2015; 3: 9-13
        • Stollar F.
        • Rodrigues J.C.
        • Cunha M.T.
        • Leone C.
        • Adde F.V.
        Six minute walk test Z score: correlations with cystic fibrosis severity markers.
        J Cyst Fibros. 2012; 11: 253-256
        • Demers C.
        • McKelvie R.S.
        • Negassa A.
        • Yusuf S.
        Reliability, validity, and responsiveness of the six-minute walk test in patients with heart failure.
        Am Heart J. 2001; 142: 698-703
        • Cahalin L.P.
        • Mathier M.A.
        • Semigran M.J.
        • Dec G.W.
        • DiSalvo T.G.
        The six-minute walk test predicts peak oxygen uptake and survival in patients with advanced heart failure.
        Chest. 1996; 110: 325-332
        • Guazzi M.
        • Dickstein K.
        • Vicenzi M.
        • Arena R.
        Six-minute walk test and cardiopulmonary exercise testing in patients with chronic heart failure: a comparative analysis on clinical and prognostic insights.
        Circ Heart Fail. 2009; 2: 549-555
        • Bellet R.N.
        • Adams L.
        • Morris N.R.
        The 6-minute walk test in outpatient cardiac rehabilitation: validity, reliability and responsiveness: a systematic review.
        Physiotherapy. 2012; 98: 277-286