European Journal of Applied Physiology

, Volume 119, Issue 8, pp 1757–1767 | Cite as

High-intensity interval training in cardiac resynchronization therapy: a randomized control trial

  • Helena Santa-Clara
  • Ana Abreu
  • Xavier MeloEmail author
  • Vanessa Santos
  • Pedro Cunha
  • Mário Oliveira
  • Rita Pinto
  • Miguel Mota Carmo
  • Bo Fernhall
Original Article



To determine the effects of high-intensity interval training (HIIT) following cardiac resynchronization therapy (CRT) implantation in patients with chronic heart failure (CHF), on noninvasive estimates of systolic ventricular function, exercise performance, severity of symptoms and quality of life.


Cardiopulmonary exercise testing, resting transthoracic echocardiogram and health-related quality of life assessment were obtained before and at 6 months after CRT implantation in 37 patients with moderate-to-severe CHF. Patients were randomized after CRT to either a 24-week HIIT group (90–95% peak heart rate, 2 days per week) or to a usual care group (CON). Mixed design 2 × 2 repeated measures ANOVA were used to test for differences within and in-between groups.


Improvements in health-related quality of life (HIIT = 98.54%, CON = 123.47%), NYHA class (HIIT = 43.44%, CON = 38.30%) HR recovery at minute 1 (HIIT = 32.32%, CON = 42.94%), pulse pressure at peak effort (HIIT = 14.06%, CON = 9.52%, LVEF (HIIT = 42.17%, CON = 51.10%) and LV Mass (HIIT = 13.26%, CON = 11.88%) were similar in both groups (p > 0.05). Significant increases in CPET duration in the HIIT group (25.94%), and increases in peak VO2 (HIIT = 8.64%, CON = 4.85%) and percent-predicted VO2 (HIIT = 10.57%, CON = 4.26%) in both groups, were observed in the intention-to-treat analysis.


Six months of HIIT in patients in CRT did not further improved indices of functional capacity and health-related quality of life, and LV structure and function, compared to CRT alone. However, HIIT led to further improvements in exercise performance. It remains unclear whether HIIT benefits patients in CRT to a similar degree as more conventional forms of exercise training previously shown to maximize benefits in CRT.

Clinical trial registration Unique identifier: NCT02413151.


Exercise capacity Chronic heart failure Reduced ejection fraction Exercise training 



Chronic heart failure




Cardiopulmonary exercise testing duration


Cardiac resynchronization therapy


High-intensity interval training


Heart rate

HR recovery 1 min

Heart rate recovery at 1 min after CPET

HR recovery 3 min

Heart rate recovery at 3 min after CPET


Left ventricular


Left ventricular ejection fraction

LV mass

Left ventricular mass


Left ventricular end-diastolic volume


Left ventricular end-systolic volume


New York Heart Association Functional Scale

Peak PP

Pulse pressure at peak effort during cardiopulmonary exercise testing

Peak RPP

Rate pressure product at peak effort during cardiopulmonary exercise testing

Peak HR

Heart rate at peak effort during cardiopulmonary exercise testing

Peak VO2

Oxygen consumption at peak effort during cardiopulmonary exercise testing


Respiratory exchange ratio



The authors would like to thank Dr. Neil Oldridge’s suggestions on the manuscript. We would also acknowledge the contributions of the cardiopulmonary technicians and the medical interns in cardiology from Hospital Santa-Marta, and Mafalda Carinha from Faculdade de Motricidade Humana, Universidade de Lisboa.

Author contributions

HSC, AA contributed to conception and design, critically revised the manuscript, and gave final approval. VS contributed to acquisition, analysis, critically revised the manuscript and gave final approval. XM contributed to acquisition, analysis, interpretation, drafted the manuscript and gave final approval. RP and BF contributed to interpretation, critically revised manuscript, and gave final approval. PC, MO, MMC contributed to acquisition, critically revised the manuscript, and gave final approval.


This research was supported by National funding from the Portuguese Foundation for Science and Technology (PTDC/DES/120249/2010).

Compliance with ethical standards

Conflict of interest

The authors have no competing interests.

Supplementary material

421_2019_4165_MOESM1_ESM.docx (15 kb)
Lost to follow-up registered during the study period (docx 15 kb)
421_2019_4165_MOESM2_ESM.docx (15 kb)
Quality of Life, Functional Class, Exercise Performance and Echocardiographic parameters including all patients in CRT as randomized. Values were expressed as mean ± SEM. * Significant time effects (p<0.05). Abbreviations: HIIT, High intensity interval Training; CRT, Cardiac resynchronization therapy; CON, Control; P change score, significance of differences between change scores (HIIT vs CON); NYHA, New York Heart Association Functional Class; Peak PP, Pulse pressure at peak effort during cardiopulmonary exercise testing; Peak RPP, Rate pressure product at peak effort during cardiopulmonary exercise testing; Peak HR, Heart rate at peak effort during cardiopulmonary exercise testing; Peak VO2, Oxygen consumption at peak effort during cardiopulmonary exercise testing; %-predicted VO2, calculated according to normative values proposed by Wasserman and Hansen et al (2012); CPET duration, Cardiopulmonary exercise testing duration; RER, Respiratory Exchange Ratio; HR recovery 1’, Heart rate recovery at 1’ after CPET; HR recovery 3’, Heart rate recovery at 3’ after CPET; LVEF, Left Ventricular Ejection Fraction; LV Mass, Left Ventricular Mass; LVEDV, Left Ventricular End-Diastolic Volume; LVESV, Left Ventricular End-Systolic Volume. (docx 15 kb)


  1. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P, Messenger J, Evaluation MSGMIRC (2002) Cardiac resynchronization in chronic heart failure. N Engl J Med 346(24):1845–1853. CrossRefGoogle Scholar
  2. Auricchio A, Stellbrink C, Sack S, Block M, Vogt J, Bakker P, Huth C, Schondube F, Wolfhard U, Bocker D, Krahnefeld O, Kirkels H (2002) Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol 39(12):2026–2033CrossRefGoogle Scholar
  3. Bartlett JD, Close GL, MacLaren DP, Gregson W, Drust B, Morton JP (2011) High-intensity interval running is perceived to be more enjoyable than moderate-intensity continuous exercise: implications for exercise adherence. J Sports Sci 29(6):547–553. CrossRefPubMedGoogle Scholar
  4. Belardinelli R, Capestro F, Misiani A, Scipione P, Georgiou D (2006) Moderate exercise training improves functional capacity, quality of life, and endothelium-dependent vasodilation in chronic heart failure patients with implantable cardioverter defibrillators and cardiac resynchronization therapy. Eur J Cardiovasc Prev Rehabil 13(5):818–825CrossRefPubMedGoogle Scholar
  5. Beneke R, Meyer K (1997) Walking performance and economy in chronic heart failure patients pre and post exercise training. Eur J Appl Physiol Occup Physiol 75(3):246–251CrossRefPubMedGoogle Scholar
  6. Bjarnason-Wehrens B, McGee H, Zwisler AD, Piepoli MF, Benzer W, Schmid JP, Dendale P, Pogosova NG, Zdrenghea D, Niebauer J, Mendes M, Cardiac Rehabilitation Section European of Cardiovascular Prevention and Rehabilitation (2010) Cardiac rehabilitation in Europe: results from the European Cardiac Rehabilitation Inventory Survey. Eur J Cardiovasc Prev Rehabil 17(4):410–418. CrossRefPubMedGoogle Scholar
  7. Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE (ESC) ESoC (EHRA) EHRA (2013) 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Europace 15(8):1070–1118. CrossRefGoogle Scholar
  8. Cleland JGF, Daubert J, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L, Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators (2005) The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352(15):1539–1549CrossRefGoogle Scholar
  9. Conraads VM, Vanderheyden M, Paelinck B, Verstreken S, Blankoff I, Miljoen H, De Sutter J, Beckers P (2007) The effect of endurance training on exercise capacity following cardiac resynchronization therapy in chronic heart failure patients: a pilot trial. Eur J Cardiovasc Prev Rehabil 14(1):99–106CrossRefPubMedGoogle Scholar
  10. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N (1986) Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 57(6):450–458CrossRefPubMedGoogle Scholar
  11. Dimopoulos S, Anastasiou-Nana M, Sakellariou D, Drakos S, Kapsimalakou S, Maroulidis G, Roditis P, Papazachou O, Vogiatzis I, Roussos C, Nanas S (2006) Effects of exercise rehabilitation program on heart rate recovery in patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil 13(1):67–73CrossRefPubMedGoogle Scholar
  12. Downing J, Balady GJ (2011) The role of exercise training in heart failure. J Am Coll Cardiol 58(6):561–569CrossRefPubMedGoogle Scholar
  13. Ellingsen Ø, Halle M, Conraads V, Støylen A, Dalen H, Delagardelle C, Larsen AI, Hole T, Mezzani A, Van Craenenbroeck EM, Videm V, Beckers P, Christle JW, Winzer E, Mangner N, Woitek F, Höllriegel R, Pressler A, Monk-Hansen T, Snoer M, Feiereisen P, Valborgland T, Kjekshus J, Hambrecht R, Gielen S, Karlsen T, Prescott E, Linke A, SMARTEX Heart Failure Study (Study of Myocardial Recovery After Exercise Training in Heart Failure) Group (2017) High-intensity interval training in patients with heart failure with reduced ejection fraction. Circulation 135(9):839–849. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Evangelista A, Flachskampf F, Lancellotti P, Badano L, Aguilar R, Monaghan M, Zamorano J, Nihoyannopoulos P, Echocardiography EAo (2008) European Association of Echocardiography recommendations for standardization of performance, digital storage and reporting of echocardiographic studies. Eur J Echocardiogr 9(4):438–448. CrossRefGoogle Scholar
  15. Gayda M, Ribeiro PA, Juneau M, Nigam A (2016) Comparison of different forms of exercise training in patients with cardiac disease: where does high-intensity interval training fit? Can J Cardiol 32(4):485–494. CrossRefPubMedGoogle Scholar
  16. Goldenberg I, Moss AJ, Hall WJ, Foster E, Goldberger JJ, Santucci P, Shinn T, Solomon S, Steinberg JS, Wilber D, Barsheshet A, McNitt S, Zareba W, Klein H, Executive Committee MADIT-CRT (2011) Predictors of response to cardiac resynchronization therapy in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Circulation 124(14):1527–1536. CrossRefPubMedGoogle Scholar
  17. Grewal J, McCully RB, Kane GC, Lam C, Pellikka PA (2009) Left ventricular function and exercise capacity. JAMA 301(3):286–294. CrossRefPubMedPubMedCentralGoogle Scholar
  18. Guiraud T, Nigam A, Gremeaux V, Meyer P, Juneau M, Bosquet L (2012) High-intensity interval training in cardiac rehabilitation. Sports Med 42(7):587–605. CrossRefPubMedGoogle Scholar
  19. Hambrecht R, Gielen S, Linke A, Fiehn E, Yu J, Walther C, Schoene N, Schuler G (2000) Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial. JAMA 283(23):3095–3101CrossRefGoogle Scholar
  20. Hussein NA, Thomas MA (2008) Rehabilitation of patients with implantable cardioverter/defibrillator: a literature review. Acta Cardiol 63(2):249–257. CrossRefPubMedGoogle Scholar
  21. Iellamo F, Manzi V, Caminiti G, Vitale C, Castagna C, Massaro M, Franchini A, Rosano G, Volterrani M (2013) Matched dose interval and continuous exercise training induce similar cardiorespiratory and metabolic adaptations in patients with heart failure. Int J Cardiol 167(6):2561–2565. CrossRefPubMedGoogle Scholar
  22. Keteyian SJ, Piña IL, Hibner BA, Fleg JL (2010) Clinical role of exercise training in the management of patients with chronic heart failure. J Cardiopulm Rehabil Prev 30(2):67–76. CrossRefPubMedGoogle Scholar
  23. Kutyifa V, Solomon SD, Bourgoun M, Shah AM, Pouleur AC, Knappe D, McNitt S, Wang PJ, Merkely B, Pfeffer M, Moss AJ, Zareba W (2013) Effects of cardiac resynchronization therapy on left ventricular mass and wall thickness in mild heart failure patients in MADIT-CRT. Heart Rhythm 10(3):354–360. CrossRefPubMedGoogle Scholar
  24. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 16(3):233–270. CrossRefPubMedGoogle Scholar
  25. Mannaerts H (2006) Regression of left ventricular mass and wall thickness after cardiac resynchronization therapy: proof of pathophysiological concept. Eur Heart J 27(12):1392–1393. CrossRefPubMedGoogle Scholar
  26. Meyer P, Gayda M, Juneau M, Nigam A (2013) High-intensity aerobic interval exercise in chronic heart failure. Curr Heart Fail Rep 10(2):130–138. CrossRefPubMedGoogle Scholar
  27. Oldridge N, Höfer S, McGee H, Conroy R, Doyle F, Saner H (2014) The HeartQoL: part II. Validation of a new core health-related quality of life questionnaire for patients with ischemic heart disease. Eur J Prev Cardiol 21(1):98–106. CrossRefGoogle Scholar
  28. Patwala AY, Woods PR, Sharp L, Goldspink DF, Tan LB, Wright DJ (2009) Maximizing patient benefit from cardiac resynchronization therapy with the addition of structured exercise training: a randomized controlled study. J Am Coll Cardiol 53(25):2332–2339CrossRefPubMedGoogle Scholar
  29. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Members ATF (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37(27):2129–2200. CrossRefGoogle Scholar
  30. Roditis P, Dimopoulos S, Sakellariou D, Sarafoglou S, Kaldara E, Venetsanakos J, Vogiatzis J, Anastasiou-Nana M, Roussos C, Nanas S (2007) The effects of exercise training on the kinetics of oxygen uptake in patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil 14(2):304–311. CrossRefPubMedGoogle Scholar
  31. Santos V, Abreu A, Pinto R, Melo X, Cunha P, Oliveira M, Selas M, Soares R, Ferreira R, Sardinha LB, Fernhall B (2015) Effect of high intensity interval training on cardiac remodeling following cardiac resynchronization therapy: RCT. Med Sci Sports Exerc. CrossRefPubMedGoogle Scholar
  32. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2(5):358–367CrossRefGoogle Scholar
  33. Smolis-Bąk E, Dąbrowski R, Piotrowicz E, Chwyczko T, Dobraszkiewicz-Wasilewska B, Kowalik I, Kazimierska B, Jędrzejczyk B, Smolis R, Gepner K, Maciąg A, Sterliński M, Szwed H (2015) Hospital-based and telemonitoring guided home-based training programs: effects on exercise tolerance and quality of life in patients with heart failure (NYHA class III) and cardiac resynchronization therapy. A randomized, prospective observation. Int J Cardiol 199:442–447. CrossRefPubMedGoogle Scholar
  34. St John Sutton MG, Plappert T, Abraham WT, Smith AL, DeLurgio DB, Leon AR, Loh E, Kocovic DZ, Fisher WG, Ellestad M, Messenger J, Kruger K, Hilpisch KE, Hill MR, Multicenter InSync Randomized Clinical Evaluation (MIRACLE) Study Group (2003) Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation 107(15):1985–1990. CrossRefPubMedGoogle Scholar
  35. St John Sutton M, Ghio S, Plappert T, Tavazzi L, Scelsi L, Daubert C, Abraham WT, Gold MR, Hassager C, Herre JM, Linde C, Group RrRiSlvdRS (2009) Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure. Circulation 120(19):1858–1865. CrossRefPubMedGoogle Scholar
  36. Wasserman K, Hansen J, Sue D, Stringer W, Sietsema K, Sun X-G, Whipp B (2012) Principles of exercise testing and interpretation. Normal values, 5th edn. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  37. Weston KS, Wisløff U, Coombes JS (2014) High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: a systematic review and meta-analysis. Br J Sports Med 48(16):1227–1234. CrossRefGoogle Scholar
  38. Wisloff U, Stoylen A, Loennechen JP, Bruvold M, Rognmo O, Haram PM, Tjonna AE, Helgerud J, Slordahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen O, Skjaerpe T (2007) Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation 115(24):3086–3094. CrossRefPubMedPubMedCentralGoogle Scholar
  39. Wisløff U, Ellingsen Ø, Kemi OJ (2009) High-intensity interval training to maximize cardiac benefits of exercise training? Exerc Sport Sci Rev 37(3):139–146. CrossRefPubMedGoogle Scholar
  40. Yu CM, Chau E, Sanderson JE, Fan K, Tang MO, Fung WH, Lin H, Kong SL, Lam YM, Hill MR, Lau CP (2002) Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 105(4):438–445CrossRefPubMedGoogle Scholar
  41. Zeitler EP, Piccini JP, Hellkamp AS, Whellan DJ, Jackson KP, Ellis SJ, Kraus WE, Keteyian SJ, Kitzman DW, Ewald GA, Fleg JL, Piña IL, O’Connor CM, Investigators H-A (2015) Exercise training and pacing status in patients with heart failure: results from HF-ACTION. J Card Fail 21(1):60–67. CrossRefPubMedGoogle Scholar
  42. Zhang Q, Fung JW, Auricchio A, Chan JY, Kum LC, Wu LW, Yu CM (2006) Differential change in left ventricular mass and regional wall thickness after cardiac resynchronization therapy for heart failure. Eur Heart J 27(12):1423–1430. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Faculdade de Motricidade Humana, CIPER, Centro Interdisciplinar de Estudo da Performance HumanaUniversidade de LisboaLisbonPortugal
  2. 2.Departamento de Cardiologia, Centro Hospitalar de Lisboa CentralHospital Santa-MartaLisbonPortugal
  3. 3.GCP Lab, Praça Ginásio Clube Português n.1Ginásio Clube PortuguêsLisbonPortugal
  4. 4.Faculdade de Ciências Médicas, CEDOC, Centro de Estudos de Doenças CrónicasUniversidade NovaLisbonPortugal
  5. 5.Integrative Physiology Laboratory, College of Applied Health SciencesUniversity of Illinois at ChicagoChicagoUSA

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