2020, Número 4
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Rev Cubana Cardiol Cir Cardiovasc 2020; 26 (4)
Entrenamiento Aeróbico y de Fuerza Combinado comparado con Aeróbico solamente en la Rehabilitación de Pacientes con Insuficiencia Cardíaca
Bizzozero PB, Díaz GV
Idioma: Español
Referencias bibliográficas: 75
Paginas: 1-14
Archivo PDF: 267.03 Kb.
RESUMEN
Objetivo: comparar la influencia del entrenamiento aeróbico y de fuerza combinados (EAFC) con el entrenamiento aeróbico sobre variables relevantes de la rehabilitación cardíaca (RC) en pacientes con insuficiencia cardíaca (IC).
Método: Realizamos una revisión de revisiones sistemáticas y meta-análisis en PubMed y Web of Science hasta marzo de 2020. Se utilizó la herramienta ‘Assessment of Multiple Systematic Reviews 2’ (AMSTAR-2) para evaluar la calidad metodológica de los estudios.
Resultados: se identificaron un total de 600 artículos, de los cuales 5 se seleccionaron para esta revisión. En los estudios incluidos se identificaron un total de 16 intervenciones diferentes con 409 pacientes (rango edad media = 51-70 años) con IC y fracción de eyección del ventrículo izquierdo reducida. Un estudio presentó nivel de confianza alto y 4 estudios presentaron nivel de confianza moderado (AMSTAR-2). El EAFC presentó mejoras significativas sobre la calidad de vida y la fuerza muscular en comparación al entrenamiento aeróbico. No se encontraron diferencias significativas al comparar los efectos de los entrenamientos sobre la capacidad aeróbica, fracción de eyección del ventrículo izquierdo y pendiente de ventilación minuto/producción dióxido de carbono.
Conclusiones: El EAFC es una intervención de ejercicio adecuada en la RC de pacientes con IC, potenciando las mejoras sobre calidad de vida y fuerza muscular en comparación al entrenamiento aeróbico. Son necesarios estudios que analicen los efectos del EAFC según característica del entrenamiento, edad, severidad de la IC y tratamiento farmacológico.
REFERENCIAS (EN ESTE ARTÍCULO)
Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol. 2016;13(6):368–78. Doi: 10.1038/nrcardio.2016.25
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37(27):2129–200. Doi: 10.1093/eurheartj/ehw128
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Card Fail. 2017;23(8):628–51. Doi: 10.1016/j.cardfail.2017.04.014
Anderson L, Taylor RS. Cardiac rehabilitation for people with heart disease: an overview of Cochrane systematic reviews. In: Taylor RS, editor. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2014. Doi: 10.1002/14651858.CD011273.pub2
Clark RA, Conway A, Poulsen V, Keech W, Tirimacco R, Tideman P. Alternative models of cardiac rehabilitation: a systematic review. Eur J Prev Cardiol. 2015;22(1):35–74. Doi: 10.1177/2047487313501093
Vanhees L, Geladas N, Hansen D, Kouidi E, Niebauer J, Reiner Ž, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR (Part II). Eur J Prev Cardiol. 2012;19(5):1005–33. Doi: 10.1177/1741826711430926
Heart Failure Society of America, Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2010;16(6):e1-194. Doi: 10.1016/j.cardfail.2010.04.004
Ades PA, Keteyian SJ, Balady GJ, Houston-Miller N, Kitzman DW, Mancini DM, et al. Cardiac Rehabilitation Exercise and Self-Care for Chronic Heart Failure. Vol. 1, JACC: Heart Failure. 2013. p. 540–7. Doi: 10.1016/j.jchf.2013.09.002
Thompson PD, Franklin BA, Balady GJ, Blair SN, Corrado D, Estes NAM, et al. Exercise and acute cardiovascular events placing the risks into perspective: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology. Circulation. 2007;115(17):2358–68. Doi: 10.1161/CIRCULATIONAHA.107.181485
Sagar VA, Davies EJ, Briscoe S, Coats AJS, Dalal HM, Lough F, et al. Exercise-based rehabilitation for heart failure: systematic review and meta-analysis. Open Hear. 2015;2(1):e000163. Doi: 10.1136/openhrt-2014-000163
Fukuta H, Goto T, Wakami K, Kamiya T, Ohte N. Effects of exercise training on cardiac function, exercise capacity, and quality of life in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials. Heart Fail Rev. 2019;24(4):535–47. Doi: 10.1007/s10741-019-09774-5
Cattadori G, Segurini C, Picozzi A, Padeletti L, Anzà C. Exercise and heart failure: an update [Internet]. Vol. 5, ESC Heart Failure. Wiley-Blackwell; 2018. p. 222–32. Doi: 10.1002/ehf2.12225
Do Prado DML, Rocco EA. The benefits of exercise training on aerobic capacity in patients with heart failure and preserved ejection fraction. In: Advances in Experimental Medicine and Biology. Springer New York LLC; 2017. p. 51–64. Doi: 10.1007/978-981-10-4304-8_4
Giuliano C, Karahalios A, Neil C, Allen J, Levinger I. The effects of resistance training on muscle strength, quality of life and aerobic capacity in patients with chronic heart failure — A meta-analysis. Vol. 227, International Journal of Cardiology. Elsevier Ireland Ltd; 2017. p. 413–23. Doi: 10.1016/j.ijcard.2016.11.023
Slimani M, Ramirez-Campillo R, Paravlic A, Hayes LD, Bragazzi NL, Sellami M. The effects of physical training on quality of life, aerobic capacity, and cardiac function in older patients with heart failure: A meta-analysis. Vol. 9, Frontiers in Physiology. Frontiers Media S.A.; 2018. Doi: 10.3389/fphys.2018.01564
Mitchell JH, Wildenthal K. Static (Isometric) Exercise and the Heart: Physiological and Clinical Considerations. Annu Rev Med. 1974;25(1):369–81. Doi: 10.1146/annurev.me.25.020174.002101
Marzolini S, Oh PI, Brooks D. Effect of combined aerobic and resistance training versus aerobic training alone in individuals with coronary artery disease: a meta-analysis. Eur J Prev Cardiol. 2012;19(1):81–94. Doi: 10.1177/1741826710393197
Fletcher GF, Ades PA, Kligfield P, Arena R, Balady GJ, Bittner VA, et al. Exercise standards for testing and training: A scientific statement from the American heart association. Circulation. 2013;128(8):873–934. Doi: 10.1161/CIR.0b013e31829b5b44
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009;6(7):e1000097. Doi: 10.1371/journal.pmed.1000097
Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;j4008. Doi: 10.1136/bmj.j4008
Ciapponi A. AMSTAR-2: herramienta de evaluación crítica de revisiones sistemáticas de estudios de intervenciones de salud. Evidencia. 2017;21(1):4–13.
Shea B, Reeves B, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR Checklist [Internet]. BMJ. 2017.
Tu RH, Zeng ZY, Zhong GQ, Wu WF, Lu YJ, Bo ZD, et al. Effects of exercise training on depression in patients with heart failure: A systematic review and meta-analysis of randomized controlled trials. Eur J Heart Fail. 2014;16(7):749–57. Doi: 10.1002/ejhf.101
Tucker WJ, Beaudry RI, Liang Y, Clark AM, Tomczak CR, Nelson MD, et al. Meta-analysis of Exercise Training on Left Ventricular Ejection Fraction in Heart Failure with Reduced Ejection Fraction: A 10-year Update. Vol. 62, Progress in Cardiovascular Diseases. W.B. Saunders; 2019. p. 163–71. Doi: 10.1016/j.pcad.2018.08.006
Pearson MJ, Mungovan SF, Smart NA. Effect of aerobic and resistance training on inflammatory markers in heart failure patients: systematic review and meta-analysis. Vol. 23, Heart Failure Reviews. Springer New York LLC; 2018. p. 209–23. Doi: 10.1007/s10741-018-9677-0
Ostman C, Jewiss D, Smart NA. The Effect of Exercise Training Intensity on Quality of Life in Heart Failure Patients: A Systematic Review and Meta-Analysis. Cardiol. 2017;136(2):79–89. Doi: 10.1159/000448088
Wang ZQ, Peng X, Li K, Wu CJJ. Effects of combined aerobic and resistance training in patients with heart failure: A meta-analysis of randomized, controlled trials. Vol. 21, Nursing and Health Sciences. Blackwell Publishing; 2019. p. 148–56. Doi: 10.1111/nhs.12593
Smart NA, Steele M. Systematic review of the effect of aerobic and resistance exercise training on systemic brain natriuretic peptide (BNP) and N-terminal BNP expression in heart failure patients. Vol. 140, International Journal of Cardiology. Elsevier Ireland Ltd; 2010. p. 260–5. Doi: 10.1016/j.ijcard.2009.07.004
Gayda M, Ribeiro PAB, Juneau M, Nigam A. Comparison of Different Forms of Exercise Training in Patients With Cardiac Disease: Where Does High-Intensity Interval Training Fit? Vol. 32, Canadian Journal of Cardiology. Pulsus Group Inc.; 2016. p. 485–94. Doi: 10.1016/j.cjca.2016.01.017
Zhang Y, Qi L, Xu L, Sun X, Liu W, Zhou S, et al. Effects of exercise modalities on central hemodynamics, arterial stiffness and cardiac function in cardiovascular disease: Systematic review and meta-analysis of randomized controlled trials. PLoS One. 2018;13(7). Doi: 10.1371/journal.pone.0200829
Jesus IC De, Menezes Junior FJ de, Bento PCB, Wiens A, Mota J, Leite N. Effect of combined interval training on the cardiorespiratory fitness in heart failure patients: a systematic review and meta-analysis. Vol. 24, Brazilian Journal of Physical Therapy. Revista Brasileira de Fisioterapia; 2020. p. 8–19. Doi: 10.1016/j.bjpt.2019.04.001
Haykowsky MJ, Liang Y, Pechter D, Jones LW, McAlister FA, Clark AM. A Meta-Analysis of the Effect of Exercise Training on Left Ventricular Remodeling in Heart Failure Patients. The Benefit Depends on the Type of Training Performed. J Am Coll Cardiol. 2007;49(24):2329–36. Doi: 10.1016/j.jacc.2007.02.055
Smart NA, Dieberg G, Giallauria F. Intermittent versus continuous exercise training in chronic heart failure: A meta-analysis. Int J Cardiol. 2013;166(2):352–8. Doi: 10.1016/j.ijcard.2011.10.075
Chen YM, Zhu M, Zhang YX. Combined endurance-resistance training improves submaximal exercise capacity in elderly heart failure patients: A systematic review of randomized controlled trials. Int J Cardiol. 2013;166(1):250–2. Doi: 10.1016/j.ijcard.2012.09.114
Jewiss D, Ostman C, Smart NA. The effect of resistance training on clinical outcomes in heart failure: A systematic review and meta-analysis. Int J Cardiol. 2016;221:674–81. Doi: 10.1016/j.ijcard.2016.07.046
Hwang CL, Chien CL, Wu YT. Resistance training increases 6-minute walk distance in people with chronic heart failure: A systematic review. J Physiother. 2010;56(2):87–96. Doi: 10.1016/S1836-9553(10)70038-2
Cornelis J, Beckers P, Taeymans J, Vrints C, Vissers D. Comparing exercise training modalities in heart failure: A systematic review and meta-analysis. Vol. 221, International Journal of Cardiology. Elsevier Ireland Ltd; 2016. p. 867–76. Doi: 10.1016/j.ijcard.2016.07.105
Santos F V., Chiappa GR, Ramalho SHR, de Lima ACGB, de Souza FSJ, Cahalin LP, et al. Resistance exercise enhances oxygen uptake without worsening cardiac function in patients with systolic heart failure: a systematic review and meta-analysis. Vol. 23, Heart Failure Reviews. Springer New York LLC; 2018. p. 73–89. Doi: 10.1007/s10741-017-9658-8
Gomes-Neto M, Duraes A, Conceicao L, Roever L, Magalhaes C, Nogueira I, et al. Effect of combined aerobic and resistance training on peak oxygen consumption, muscle strength and health-related quality of life in patients with heart failure with reduced left ventricular ejection fraction: a systematic review and meta-analysis. Int J Cardiol. 2019;293:165–75. Doi: 10.1016/j.ijcard.2019.02.050
Springer J, Springer JI, Anker SD. Muscle wasting and sarcopenia in heart failure and beyond: update 2017 [Internet]. Vol. 4, ESC Heart Failure. Wiley-Blackwell; 2017. p. 492–8. Doi: 10.1002/ehf2.12237
Suzuki T, Palus S, Springer J. Skeletal muscle wasting in chronic heart failure. Vol. 5, ESC Heart Failure. Wiley-Blackwell; 2018. p. 1099–107. Doi: 10.1002/ehf2.12387
Hülsmann M, Quittan M, Berger R, Crevenna R, Springer C, Nuhr M, et al. Muscle strength as a predictor of long-term survival in severe congestive heart failure. Eur J Heart Fail. 2004;6(1):101–7. Doi: 10.1016/j.ejheart.2003.07.008
Heitmann BL, Frederiksen P. Thigh circumference and risk of heart disease and premature death: Prospective cohort study. BMJ. 2009;339(7723):736. Doi: 10.1136/bmj.b3292
Reddy YNV, Rikhi A, Obokata M, Shah SJ, Lewis GD, AbouEzzedine OF, et al. Quality of life in heart failure with preserved ejection fraction: importance of obesity, functional capacity, and physical inactivity. Eur J Heart Fail. 2020; Doi: 10.1002/ejhf.1788
Faller H, Störk S, Schowalter M, Steinbüchel T, Wollner V, Ertl G, et al. Is health-related quality of life an independent predictor of survival in patients with chronic heart failure? J Psychosom Res. 2007;63(5):533–8. Doi: 10.1016/j.jpsychores.2007.06.026
Molina AJA, Bharadwaj MS, Van Horn C, Nicklas BJ, Lyles MF, Eggebeen J, et al. Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance. JACC Heart Fail. 2016;4(8):636–45. Doi: 10.1016/j.jchf.2016.03.011
Haykowsky MJ, Nicklas BJ, Brubaker PH, Hundley WG, Brinkley TE, Upadhya B, et al. Regional Adipose Distribution and its Relationship to Exercise Intolerance in Older Obese Patients Who Have Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2018;6(8):640–9. Doi: 10.1016/j.jchf.2018.06.002
Borlaug BA, Olson TP, Lam CSP, Flood KS, Lerman A, Johnson BD, et al. Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2010;56(11):845–54. Doi: 10.1016/j.jacc.2010.03.077
Reddy YNV, Olson TP, Obokata M, Melenovsky V, Borlaug BA. Hemodynamic Correlates and Diagnostic Role of Cardiopulmonary Exercise Testing in Heart Failure With Preserved Ejection Fraction. JACC Hear Fail. 2018;6(8):665–75. Doi: 10.1016/j.jchf.2018.03.003
Filippatos G, Maggioni AP, Lam CSP, Pieske-Kraigher E, Butler J, Spertus J, et al. Patient-reported outcomes in the SOluble guanylate Cyclase stimulatoR in heArT failurE patientS with PRESERVED ejection fraction (SOCRATES-PRESERVED) study. Eur J Heart Fail. 2017;19(6):782–91. Doi: 10.1002/ejhf.800
Lewis EF, Lamas GA, O’Meara E, Granger CB, Dunlap ME, McKelvie RS, et al. Characterization of health-related quality of life in heart failure patients with preserved versus low ejection fraction in CHARM. Eur J Heart Fail. 2007;9(1):83–91. Doi: 10.1016/j.ejheart.2006.10.012
Mandic S, Myers J, Selig SE, Levinger I. Resistance versus aerobic exercise training in chronic heart failure [Internet]. Vol. 9, Current Heart Failure Reports. 2012. p. 57–64. Doi: 10.1007/s11897-011-0078-0
Wang Z, Peng X, Li K, Wu C-JJ. Effects of combined aerobic and resistance training in patients with heart failure: A meta-analysis of randomized, controlled trials. Nurs Health Sci. 2019;21(2):148–56. Doi: 10.1111/nhs.12593
Agostoni P, Corrà U, Cattadori G, Veglia F, La Gioia R, Scardovi AB, et al. Metabolic exercise test data combined with cardiac and kidney indexes, the MECKI score: A multiparametric approach to heart failure prognosis. Int J Cardiol. 2013;167(6):2710–8. Doi: 10.1016/j.ijcard.2012.06.113
Haykowsky MJ, Daniel KM, Bhella PS, Sarma S, Kitzman DW. Heart Failure: Exercise-Based Cardiac Rehabilitation: Who, When, and How Intense? Can J Cardiol. 2016;32(10 Suppl 2):S382–7. Doi: 10.1016/j.cjca.2016.06.001
Crimi E, Ignarro LJ, Cacciatore F, Napoli C. Mechanisms by which exercise training benefits patients with heart failure. Nat Rev Cardiol. 2009;6(4):292–300. Doi: 10.1038/nrcardio.2009.8
Swank AM, Horton J, Fleg JL, Fonarow GC, Keteyian S, Goldberg L, et al. Modest Increase in Peak VO 2 Is Related to Better Clinical Outcomes in Chronic Heart Failure Patients. Circ Hear Fail. 2012;5(5):579–85. Doi: 10.1161/CIRCHEARTFAILURE.111.965186
Kavanagh T, Mertens DJ, Hamm LF, Beyene J, Kennedy J, Corey P, et al. Prediction of long-term prognosis in 12 169 men referred for cardiac rehabilitation. Circulation. 2002;106(6):666–71. Doi: 10.1161/01.cir.0000024413.15949.ed
White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation. 1987;76(1):44–51. Doi: 10.1161/01.cir.76.1.44
Pascual-Figal DA, Ferrero-Gregori A, Gomez-Otero I, Vazquez R, Delgado-Jimenez J, Alvarez-Garcia J, et al. Mid-range left ventricular ejection fraction: Clinical profile and cause of death in ambulatory patients with chronic heart failure. Int J Cardiol. 2017;240:265–70. Doi: 10.1016/J.IJCARD.2017.03.032
Perelshtein Brezinov O, Klempfner R, Zekry S Ben, Goldenberg I, Kuperstein R. Prognostic value of ejection fraction in patients admitted with acute coronary syndrome: A real world study. Medicine (Baltimore). 2017;96(9):e6226. Doi: 10.1097/MD.0000000000006226
Poggio R, Arazi HC, Giorgi M, Miriuka SG. Prediction of severe cardiovascular events by VE/VCO2 slope versus peak VO2 in systolic heart failure: a meta-analysis of the published literature. Am Heart J. 2010;160(6):1004–14. Doi: 10.1016/j.ahj.2010.08.037
Gomes-Neto M, Durães AR, Conceição LSR, Roever L, Liu T, Tse G, et al. Effect of Aerobic Exercise on Peak Oxygen Consumption, VE/VCO2 Slope, and Health-Related Quality of Life in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction: a Systematic Review and Meta-Analysis [Internet]. Vol. 21, Current Atherosclerosis Reports. Current Medicine Group LLC 1; 2019. p. 45. Doi: 10.1007/s11883-019-0806-6
Höllriegel R, Winzer EB, Linke A, Adams V, Mangner N, Sandri M, et al. Long-Term Exercise Training in Patients With Advanced Chronic Heart Failure: sustained benefits on left ventricular performance and exercise capacity. J Cardiopulm Rehabil Prev. 2016;36(2):117–24. Doi: 10.1097/HCR.0000000000000165
Vanhees L, Rauch B, Piepoli M, van Buuren F, Takken T, Börjesson M, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III). Eur J Prev Cardiol. 2012;19(6):1333–56. Doi: 10.1177/2047487312437063
Ambrosetti M, Doherty P, Faggiano P, Corrà U, Vigorito C, Hansen D, et al. Characteristics of structured physical training currently provided in cardiac patients: insights from the Exercise Training in Cardiac Rehabilitation (ETCR) Italian survey. Monaldi Arch chest Dis (Archivio Monaldi per le Mal del torace). 2017;87(1):778. Doi: 10.4081/monaldi.2017.778
Gomes Neto M, Durães AR, Conceição LSR, Saquetto MB, Ellingsen Ø, Carvalho VO. High intensity interval training versus moderate intensity continuous training on exercise capacity and quality of life in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis. Int J Cardiol. 2018;261:134–41. Doi: 10.1016/j.ijcard.2018.02.076
Liu CJ, Latham NK. Progressive resistance strength training for improving physical function in older adults. COCHRANE DATABASE Syst Rev. 2009;(3). Doi: 10.1002/14651858.CD002759.pub2
Arena R, Myers J, Forman DE, Lavie CJ, Guazzi M. Should high-intensity-aerobic interval training become the clinical standard in heart failure? Heart Fail Rev. 2013;18(1):95–105. Doi: 10.1007/s10741-012-9333-z
Kraal JJ, Vromen T, Spee R, Kemps HMC, Peek N. The influence of training characteristics on the effect of exercise training in patients with coronary artery disease: Systematic review and meta-regression analysis. Int J Cardiol. 2017;245:52–8. Doi: 10.1016/j.ijcard.2016.01.207
Vromen T, Kraal JJ, Kuiper J, Spee RF, Peek N, Kemps HM. The influence of training characteristics on the effect of aerobic exercise training in patients with chronic heart failure: A meta-regression analysis. Int J Cardiol. 2016;208:120–7. Doi: 10.1016/j.ijcard.2016.01.207
Alvarez P, Hannawi B, Guha A. Exercise And Heart Failure: Advancing Knowledge And Improving Care [Internet]. Vol. 12, Methodist DeBakey cardiovascular journal. Methodist Debakey Cardiovasc J; 2016. p. 110–5. Doi: 10.14797/mdcj-12-2-110
Tierney S, Mamas M, Skelton D, Woods S, Rutter MK, Gibson M, et al. What can we learn from patients with heart failure about exercise adherence? A systematic review of qualitative papers. Health Psychol. 2011;30(4):401–10. Doi: 10.1037/a0022848
Tierney S, Mamas M, Woods S, Rutter MK, Gibson M, Neyses L, et al. What strategies are effective for exercise adherence in heart failure? A systematic review of controlled studies [Internet]. Vol. 17, Heart Failure Reviews. 2012. p. 107–15. Doi: 10.1007/s10741-011-9252-4
Pozehl BJ, Duncan K, Hertzog M, McGuire R, Norman JF, Artinian NT, et al. Study of adherence to exercise in heart failure: The HEART camp trial protocol. BMC Cardiovasc Disord. 2014;14(1):1–11. Doi: 10.1186/1471-2261-14-172