Advertisement
Canadian Journal of Cardiology

Therapies for Advanced Heart Failure Patients Ineligible for Heart Transplantation: Beyond Pharmacotherapy

Published:November 20, 2019DOI:https://doi.org/10.1016/j.cjca.2019.11.012

      Abstract

      Globally, there are ∼ 26 million people living with heart failure (HF), 50% of them with reduced ejection fraction, costing countries billions of dollars each year. Improvements in treatment of cardiovascular diseases, including advanced HF, have allowed an unprecedented number of patients to survive into old age. Despite these advances, patients with HF deteriorate and often require advanced therapies. As the proportion of elderly patients in the population increases, there will be an increasing number of patients to be evaluated for advanced therapies and an increasing number that do not qualify for, won’t be considered for, or decline orthotopic heart transplantation. The purpose of this article is to review the benefits of palliative care (PC), exercise-based cardiac rehabilitation (ExCR), device therapy (cardiac resynchronization therapy and mitral clip), and mechanical circulatory support (MCS) in advanced HF patients who are transplant ineligible. PC interventions should be introduced early in the course of a patient’s diagnosis to manage symptoms, address goals of care, and improve patient-centered outcomes. Further improvement in health-related quality of life as well as functional capacity can be achieved safely in patients with advanced HF through patient participation in ExCR. Device therapy and MCS can reduce HF hospitalizations and improve survival. In fact, early survival with MCS approaches that of heart transplantation. Despite their being transplant ineligible, there are a variety of treatment options available to patients to improve their quality of life, decrease hospitalizations, and potentially improve mortality.

      Résumé

      Quelque 26 millions de personnes dans le monde vivent avec une insuffisance cardiaque (IC); la moitié d’entre elles ont une fraction d’éjection réduite, ce qui coûte des milliards de dollars chaque année. Grâce aux améliorations du traitement des maladies cardiovasculaires, y compris l’IC avancée, les patients sont de plus en plus nombreux à atteindre un âge avancé. Malgré les progrès réalisés, l’état des patients atteints d’IC continue de se détériorer et exige souvent des traitements avancés. En raison du vieillissement de la population, le nombre de patients qui devront être évalués afin de déterminer s’ils sont bons candidats pour recevoir un traitement avancé ira en augmentant, tout comme le nombre de patients qui ne seront pas admissibles à une transplantation cardiaque orthotopique, qui refuseront une telle intervention ou à qui cette option ne sera pas proposée. Les auteurs passent en revue les bienfaits des soins palliatifs, de la réadaptation cardiaque axée sur l’activité physique, des dispositifs thérapeutiques (resynchronisation cardiaque et pince à valve mitrale) et de l’assistance circulatoire mécanique (ACM) chez les patients atteints d’IC avancée qui ne sont pas admissibles à une transplantation. Les interventions en soins palliatifs doivent être mises en œuvre rapidement après le diagnostic, afin de prendre en charge les symptômes, de répondre aux besoins en matière de soins et d’améliorer les résultats pour le patient. D’autres améliorations de la qualité de vie liée à la santé et de la capacité fonctionnelle peuvent aussi être obtenues en toute sécurité chez les patients atteints d’IC avancée grâce à la réadaptation cardiaque axée sur l’activité physique. Les dispositifs thérapeutiques et l’ACM peuvent réduire les hospitalisations pour IC et améliorer la survie. En fait, la survie aux stades initiaux grâce à l’ACM se rapproche de celle d’une transplantation cardiaque. Bien que ces patients ne soient pas admissibles à une transplantation, diverses autres options thérapeutiques s’offrent à eux afin d’améliorer leur qualité de vie et de réduire les hospitalisations ainsi que, possiblement, la mortalité.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ponikowski P.
        • Anker S.D.
        • AlHabib K.F.
        • et al.
        Heart failure: preventing disease and death worldwide.
        ESC Heart Fail. 2014; 1: 4-25
        • Benjamin E.J.
        • Muntner P.
        • Alonso A.
        • et al.
        Heart disease and stroke statistics—2019 update: a report from the American Heart Association.
        Circulation. 2019; 139: e56-e528
        • Blais C.
        • Dai S.
        • Waters C.
        • et al.
        Assessing the burden of hospitalized and community-care heart failure in Canada.
        Can J Cardiol. 2014; 30: 352-358
        • Allen L.A.
        • Stevenson L.W.
        • Grady K.L.
        • et al.
        Decision making in advanced heart failure: a scientific statement from the American Heart Association.
        Circulation. 2012; 125: 1928-1952
        • Komajda M.
        • Böhm M.
        • Borer J.S.
        • et al.
        Incremental benefit of drug therapies for chronic heart failure with reduced ejection fraction: a network meta-analysis.
        Eur J Heart Fail. 2018; 20: 1315-1322
        • Zannad F.
        • McMurray J.J.V.
        • van Veldhuisen D.J.
        • et al.
        Eplerenone in patients with systolic heart failure and mild symptoms.
        N Engl J Med. 2011; 364: 11-21
        • McMurray J.J.V.
        • Packer M.
        • Desai A.S.
        • et al.
        Angiotensin-neprilysin inhibition versus enalapril in heart failure.
        N Engl J Med. 2014; 371: 993-1004
        • Swedberg K.
        • Komajda M.
        • Böhm M.
        • et al.
        Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study.
        Lancet. 2010; 376: 875-885
        • McMurray J.J.V.
        • Solomon S.D.
        • Inzucchi S.E.
        • et al.
        Dapagliflozin in patients with heart failure and reduced ejection fraction.
        N Engl J Med. 2019; : 1-13
        • Jaarsma T.
        • Beattie J.M.
        • Ryder M.
        • et al.
        Palliative care in heart failure: a position statement from the palliative care workshop of the Heart Failure Association of the European Society of Cardiology.
        Eur J Heart Fail. 2009; 11: 433-443
        • Lam P.H.
        • Taffet G.E.
        • Ahmed A.
        • Singh S.
        Cardiac resynchronization therapy in older adults with heart failure.
        Heart Fail Clin. 2017; 13: 581-587
        • Garbade J.
        • Barten M.J.
        • Bittner H.B.
        • Mohr F.W.
        Heart transplantation and left ventricular assist device therapy: two comparable options in end-stage heart failure?.
        Clin Cardiol. 2013; 36: 378-382
        • Kim I.C.
        • Youn J.C.
        • Kobashigawa J.A.
        The past, present and future of heart transplantation.
        Korean Circ J. 2018; 48: 565-589
        • Canadian Institute for Health Information
        Deceased organ donor potential in Canada.
        (Available at:) (Accessed June 10, 2019)
        • Khush K.K.
        Donor selection in the modern era.
        Ann Cardiothorac Surg. 2018; 7: 126-134
        • Ezekowitz J.A.
        • O’Meara E.
        • McDonald M.A.
        • et al.
        2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of heart failure.
        Can J Cardiol. 2017; 33: 1342-1433
        • Ponikowski P.
        • Voors A.A.
        • Anker S.D.
        • et al.
        2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure.
        Eur Heart J. 2016; 37: 2129-2200
        • World Health Organization. Cancer
        WHO definition of palliative care.
        (Available at:)
        • Warraich H.J.
        • Hernandez A.F.
        • Allen L.A.
        How medicine has changed the end of life for patients with cardiovascular disease.
        J Am Coll Cardiol. 2017; 70: 1276-1289
        • Gelfman L.P.
        • Kavalieratos D.
        • Teuteberg W.G.
        • Lala A.
        • Goldstein N.E.
        Primary palliative care for heart failure: what is it? How do we implement it?.
        Heart Fail Rev. 2017; 22: 611-620
        • Chow J.
        • Senderovich H.
        It’s time to talk: challenges in providing integrated palliative care in advanced congestive heart failure. A narrative review.
        Curr Cardiol Rev. 2018; 14: 128-137
        • Brännström M.
        • Boman K.
        Effects of person-centred and integrated chronic heart failure and palliative home care. PREFER: a randomized controlled study.
        Eur J Heart Fail. 2014; 16: 1142-1151
        • Sidebottom A.C.
        • Jorgenson A.
        • Richards H.
        • Kirven J.
        • Sillah A.
        Inpatient Palliative care for patients with acute heart failure: outcomes from a randomized trial.
        J Palliat Med. 2015; 18: 134-142
        • Wong F.K.Y.
        • Ng A.Y.M.
        • Lee P.H.
        • et al.
        Effects of a transitional palliative care model on patients with end-stage heart failure: a randomised controlled trial.
        Heart. 2016; 102: 1100-1108
        • Rogers J.G.
        • Patel C.B.
        • Mentz R.J.
        • et al.
        Palliative care in heart failure: the PAL-HF randomized, controlled clinical trial.
        J Am Coll Cardiol. 2017; 70: 331-341
        • Kavalieratos D.
        • Gelfman L.P.
        • Tycon L.E.
        • et al.
        Palliative care in heart failure: rationale, evidence, and future priorities.
        J Am Coll Cardiol. 2017; 70: 1919-1930
        • Rush B.
        • Walley K.R.
        The emerging role of palliative care in the management of canadians with heart failure.
        Can J Cardiol. 2018; 34: 1114-1115
        • Nazim A.
        • Demers C.
        • Berbenetz N.
        • You J.J.
        Patterns of care during the terminal hospital admission for patients with advanced heart failure: a retrospective cohort study.
        Can J Cardiol. 2018; 34: 1215-1218
        • CorHealth Ontario
        Heart failure: care in the community for adults.
        (Available at:) (Accessed September 12, 2019)
        • Huitema A.A.
        • Harkness K.
        • Heckman G.A.
        • McKelvie R.S.
        The spoke-hub-and-node model of integrated heart failure care.
        Can J Cardiol. 2018; 34: 863-870
        • Heckman G.A.
        • Shamji A.K.
        • Ladha R.
        • et al.
        Heart failure management in nursing homes: a scoping literature review.
        Can J Cardiol. 2018; 34: 871-880
        • Iqbal J.
        • Francis L.
        • Reid J.
        • Murray S.
        • Denvir M.
        Quality of life in patients with chronic heart failure and their carers: a 3-year follow-up study assessing hospitalization and mortality.
        Eur J Heart Fail. 2010; 12: 1002-1008
        • Glogowska M.
        • Simmonds R.
        • McLachlan S.
        • et al.
        “Sometimes we can’t fix things”: a qualitative study of health care professionals’ perceptions of end of life care for patients with heart failure.
        BMC Palliat Care. 2016; 15: 1-10
        • Mitter S.S.
        • Yancy C.W.
        Contemporary approaches to patients with heart failure.
        Cardiol Clin. 2017; 35: 261-271
        • Heckman G.A.
        • Tannenbaum C.
        • Costa A.P.
        • Harkness K.
        • McKelvie R.S.
        The journey of the frail older adult with heart failure: implications for management and health care systems.
        Rev Clin Gerontol. 2014; 24: 269-289
        • Levenson J.W.
        • McCarthy E.P.
        • Lynn J.
        • Davis R.B.
        • Phillips R.S.
        The last six months of life for patients with congestive heart failure.
        J Am Geriatr Soc. 2000; 48: S101-S109
        • Forman D.E.
        • Sanderson B.K.
        • Raikhelkar J.
        • Bittner V.
        Heart failure as a newly approved diagnosis for cardiac rehabilitation challenges and opportunities.
        J Am Coll Cardiol. 2015; 65: 2652-2659
        • O’Connor C.M.
        • Whellan D.J.
        • Lee K.L.
        • et al.
        Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial.
        JAMA. 2009; 301: 1439-1450
        • Long L.
        • Mordi I.R.
        • Bridges C.
        • et al.
        Exercise-based cardiac rehabilitation for adults with heart failure.
        Cochrane Database Syst Rev. 2019; 1 (CD003331)
        • Taylor R.S.
        • Walker S.
        • Smart N.A.
        • et al.
        Impact of exercise rehabilitation on exercise capacity and quality-of-life in heart failure: individual participant meta-analysis.
        J Am Coll Cardiol. 2019; 73: 1430-1443
        • Bohannon R.W.
        • Crouch R.
        Minimal clinically important difference for change in 6-minute walk test distance of adults with pathology: a systematic review.
        J Eval Clin Pract. 2017; 23: 377-381
        • Rector T.S.
        FDA Medical Device Development Tool (MDDT) qualification package for the Minnesota Living with Heart Failure Questionnaire (MLHFQ).
        (Available at:)
        • Taylor R.S.
        • Walker S.
        • Ciani O.
        • et al.
        Exercise-based cardiac rehabilitation for chronic heart failure: the EXTRAMATCH II individual participant data meta-analysis.
        Health Technol Assess (Rockv). 2019; 23: 1-98
        • Pina I.L.
        • Kokkinos P.
        • Kao A.
        • et al.
        Baseline differences in the HF-ACTION trial by sex.
        Am Heart J. 2009; 158: S16-S23
        • Ponikowski P.
        • Voors A.A.
        • Anker S.D.
        • et al.
        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 J Heart Fail. 2016; 18: 891-975
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • et al.
        2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
        Circulation. 2013; 128: e240-e327
        • Grace S.L.
        • Midence L.
        • Oh P.
        • et al.
        Cardiac rehabilitation program adherence and functional capacity among women: a randomized controlled trial.
        Mayo Clin Proc. 2016; 91: 140-148
        • Colella T.J.
        • Gravely S.
        • Marzolini S.
        • et al.
        Sex bias in referral of women to outpatient cardiac rehabilitation? A meta-analysis.
        Eur J Prev Cardiol. 2015; 22: 423-441
        • Taylor R.S.
        • Sadler S.
        • Dalal H.M.
        • et al.
        The cost effectiveness of REACH-HF and home-based cardiac rehabilitation compared with the usual medical care for heart failure with reduced ejection fraction: a decision model–based analysis.
        Eur J Prev Cardiol. 2019; 26: 1252-1261
        • Lima de Melo Ghisi G.
        • Pesah E.
        • Turk-Adawi K.
        • et al.
        Cardiac rehabilitation models around the globe.
        J Clin Med. 2018; 7: 260
        • Grace S.L.
        • Turk-Adawi K.
        • Santiago de Araújo Pio C.
        • Alter D.A.
        Ensuring cardiac rehabilitation access for the majority of those in need: a call to action for Canada.
        Can J Cardiol. 2016; 32: S358-S364
        • Grace S.L.
        • Chessex C.
        • Arthur H.
        • et al.
        Systematizing inpatient referral to cardiac rehabilitation 2010: Canadian Association of Cardiac Rehabilitation and Canadian Cardiovascular Society joint position paper.
        Can J Cardiol. 2011; 27: 192-199
        • Grace S.L.
        • Bennett S.
        • Ardern C.I.
        • Clark A.M.
        Cardiac rehabilitation series: Canada.
        Prog Cardiovasc Dis. 2014; 56: 530-535
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • et al.
        2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.
        J Am Coll Cardiol. 2017; 70: 776-803
        • António N.
        • Elvas L.
        • Gonçalves L.
        • Providência L.A.
        Cardiac resynchronization therapy in the elderly: a realistic option for an increasing population?.
        Int J Cardiol. 2012; 155: 49-51
        • Tang A.S.L.
        • Wells G.A.
        • Talajic M.
        • et al.
        Cardiac-resynchronization therapy for mild-to-moderate heart failure.
        New Engl J Med. 2008; 363: 2385-2395
        • Gold M.R.
        • Daubert C.
        • Abraham W.T.
        • et al.
        The effect of reverse remodeling on long-term survival in mildly symptomatic patients with heart failure receiving cardiac resynchronization therapy: results of the REVERSE study.
        Heart Rhythm. 2015; 12: 524-530
        • Barsheshet A.
        • Wang P.J.
        • Moss A.J.
        • et al.
        Reverse remodeling and the risk of ventricular tachyarrhythmias in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial—Cardiac Resynchronization Therapy).
        J Am Coll Cardiol. 2011; 57: 2416-2423
        • Hayes D.L.
        • Boehmer J.P.
        • Day J.D.
        • et al.
        Cardiac resynchronization therapy and the relationship of percent biventricular pacing to symptoms and survival.
        Heart Rhythm. 2011; 8: 1469-1475
        • Cleland J.G.F.
        • Daubert J.-C.
        • Erdmann E.
        • Freemantle N.
        • Gras D.
        The effect of cardiac resynchronization on morbidity and mortality in heart failure.
        Congest Heart Fail. 2005; 352: 1539-1549
        • Bristow M.R.
        • Saxon L.A.
        • Boehmer J.
        • et al.
        for the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure.
        N Engl J Med. 2004; 350: 2140-2150
        • Fantoni C.
        • Regoli F.
        • Ghanem A.
        • et al.
        Long-term outcome in diabetic heart failure patients treated with cardiac resynchronization therapy.
        Eur J Heart Fail. 2008; 10: 298-307
        • Obeng-Gyimah E.K.
        • Deo R.
        Cardiorenal resynchronization therapy: strengthening the heart and kidneys.
        Clin J Am Soc Nephrol. 2015; 10: 1705-1707
        • Höke U.
        • Khidir M.J.H.
        • van der Velde E.T.
        • et al.
        Cardiac resynchronization therapy in CKD stage 4 patients.
        Clin J Am Soc Nephrol. 2015; 10: 1740-1748
        • Cheng A.
        • Landman S.R.
        • Stadler R.W.
        Reasons for loss of cardiac resynchronization therapy pacing.
        Circ Arrhythmia Electrophysiol. 2012; 5: 884-888
        • Khazanie P.
        • Greiner M.A.
        • Al-Khatib S.M.
        • et al.
        Comparative effectiveness of cardiac resynchronization therapy among patients with heart failure and atrial fibrillation.
        Circ Heart Fail. 2016; 9: 1-9
        • Upadhyay G.A.
        • Choudhry N.K.
        • Auricchio A.
        • Ruskin J.
        • Singh J.P.
        Cardiac resynchronization in patients with atrial fibrillation. a meta-analysis of prospective cohort studies.
        J Am Coll Cardiol. 2008; 52: 1239-1246
        • Zaca V.
        • Murphy T.
        • Biffi M.
        Electrical manipulation of the failing heart.
        Heart Fail Rev. 2018; 23: 885-896
        • Ganesan A.N.
        • Brooks A.G.
        • Roberts-Thomson K.C.
        • et al.
        Role of AV nodal ablation in cardiac resynchronization in patients with coexistent atrial fibrillation and heart failure: a systematic review.
        J Am Coll Cardiol. 2012; 59: 719-726
        • Rossi A.
        • Dini F.L.
        • Faggiano P.
        • et al.
        Independent prognostic value of functional mitral regurgitation in patients with heart failure. A quantitative analysis of 1256 patients with ischaemic and nonischaemic dilated cardiomyopathy.
        Heart. 2011; 97: 1675-1680
        • Grigioni F.
        • Enriquez-Sarano M.
        • Zehr K.J.
        • Bailey K.R.
        • Tajik A.J.
        Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment.
        Circulation. 2001; 103: 1759-1764
        • Feldman T.
        • Foster E.
        • Glower D.D.
        • et al.
        Percutaneous repair or surgery for mitral regurgitation.
        N Engl J Med. 2011; 364: 1395-1406
        • Maisano F.
        • Franzen O.
        • Baldus S.
        • et al.
        Percutaneous mitral valve interventions in the real world.
        J Am Coll Cardiol. 2013; 62: 1052-1061
        • Puls M.
        • Lubos E.
        • Boekstegers P.
        • et al.
        One-year outcomes and predictors of mortality after Mitraclip therapy in contemporary clinical practice: results from the German transcatheter mitral valve interventions registry.
        Eur Heart J. 2016; 37: 703-712
        • Nickenig G.
        • Estevez-Loureiro R.
        • Lüscher T.F.
        • et al.
        Percutaneous mitral valve edge-to-edge repair.
        J Am Coll Cardiol. 2014; 64: 875-884
        • Stone G.W.
        • Lindenfeld J.
        • Abraham W.T.
        • et al.
        Transcatheter mitral-valve repair in patients with heart failure.
        N Engl J Med. 2018; 379: 2307-2318
        • Baumgartner H.
        • Falk V.
        • Bax J.J.
        • et al.
        2017 ESC/EACTS guidelines on the management of valvular heart disease.
        Eur Heart J. 2017; 38: 2739-2791
        • Nishimura R.A.
        • Otto C.M.
        • Bonow R.O.
        • et al.
        2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        J Am Coll Cardiol. 2017; 70: 252-289
        • Obadia J.F.
        • Messika-Zeitoun D.
        • Leurent G.
        • et al.
        Percutaneous repair or medical treatment for secondary mitral regurgitation.
        N Engl J Med. 2018; 379: 2297-2306
        • Arnold S.V.
        • Chinnakondepalli K.M.
        • Spertus J.A.
        • et al.
        Health status after transcatheter mitral-valve repair in heart failure and secondary mitral regurgitation: COAPT trial.
        J Am Coll Cardiol. 2019; 73: 2123-2132
        • Almarzooq Z.
        • Pareek M.
        • Sinnenberg L.
        • Vaduganathan M.
        • Mehra M.R.
        Nine contemporary therapeutic directions in heart failure.
        Heart Asia. 2019; 11 (e011150)
        • Goliasch G.
        • Bartko P.E.
        • Pavo N.
        • et al.
        Refining the prognostic impact of functional mitral regurgitation in chronic heart failure.
        Eur Heart J. 2018; 39: 39-46
        • Shah M.
        • Jorde U.P.
        Percutaneous mitral valve interventions (repair): current indications and future perspectives.
        Front Cardiovasc Med. 2019; 6: 88
        • Atianzar K.
        • Zhang M.
        • Newhart Z.
        • Gafoor S.
        Why did COAPT Win while MITRA-FR failed? Defining the appropriate patient population for Mitraclip.
        Interv Cardiol Rev. 2019; 14: 45
        • Arora G.
        • Patel N.
        • Arora P.
        Futile MITRA-FR and a positive COAPT trial: where does the evidence leave the clinicians?.
        IJC Heart Vasc. 2019; 22: 18-19
        • Anker S.
        • Schillinger W.
        A clinical evaluation of the safety and effectiveness of the Mitraclip system in the treatment of clinically significant functional mitral regurgitation (Reshape-HF2).
        (Available at:)
        https://clinicaltrials.gov/show/nct02444338
        Date: 2015
        Date accessed: June 14, 2019
        • Fang J.C.
        Rise of the machines—left ventricular assist devices as permanent therapy for advanced heart failure.
        N Engl J Med. 2009; 361: 2282-2285
        • Cai A.W.
        • Islam S.
        • Hankins S.R.
        • Fischer W.
        • Eisen H.J.
        Mechanical circulatory support in the treatment of advanced heart failure.
        Am J Transplant. 2017; 17: 3020-3032
        • Rose E.A.
        • Gelijns A.C.
        • Moskowitz A.J.
        • et al.
        Long-term use of a left ventricular assist device.
        N Engl J Med. 2001; 345: 1435-1443
        • Rogers J.G.
        • Butler J.
        • Lansman S.L.
        • et al.
        Chronic mechanical circulatory support for inotrope-dependent heart failure patients who are not transplant candidates. Results of the INTREPID trial.
        J Am Coll Cardiol. 2007; 50: 741-747
        • Pagani F.D.
        • Miller L.W.
        • Russell S.D.
        • et al.
        Extended mechanical circulatory support with a continuous-flow rotary left ventricular assist device.
        J Am Coll Cardiol. 2009; 54: 312-321
        • Slaughter M.S.
        • Rogers J.G.
        • Milano C.A.
        • et al.
        Advanced heart failure treated with continuous-flow left ventricular assist device.
        N Engl J Med. 2009; 361: 2241-2251
        • Rogers J.G.
        • Pagani F.D.
        • Tatooles A.J.
        • et al.
        Intrapericardial left ventricular assist device for advanced heart failure.
        N Engl J Med. 2017; 376: 451-460
        • Milano C.A.
        • Rogers J.G.
        • Tatooles A.J.
        • et al.
        HVAD: the ENDURANCE supplemental trial.
        JACC Heart Fail. 2018; 6: 792-802
        • International Society of Heart and Lung Transplantation
        Overall heart transplantation statistics.
        (Available at:) (Accessed November 11, 2019)
        • Mehra M.R.
        • Goldstein D.J.
        • Uriel N.
        • et al.
        Two-year outcomes with a magnetically levitated cardiac pump in heart failure.
        N Engl J Med. 2018; 378: 1386-1395
        • Lee L.S.
        • Shekar P.S.
        Current state-of-the-art of device therapy for advanced heart failure.
        Croat Med J. 2014; 55: 577-586
        • Trillium Gift of Life Network
        Addendum: Ontario clinical guidelines: ventricular assist devices for destination therapy.
        AddendumOntario Clinical Guidelines Ventricular Assist Devices for Destination Therapy. June 16, 2017; (Available at:) (Accessed September 1, 2019)
        • Dubois R.W.
        Cost-effectiveness thresholds in the USA: are they coming? Are they already here?.
        J Comp Eff Res. 2016; 5: 9-11
        • Rogers J.G.
        • Bostic R.R.
        • Tong K.B.
        • et al.
        Cost-effectiveness analysis of continuous-flow left ventricular assist devices as destination therapy.
        Circ Heart Fail. 2012; 5: 10-16
        • Long E.F.
        • Swain G.W.
        • Mangi A.A.
        Comparative survival and cost-effectiveness of advanced therapies for end-stage heart failure.
        Circ Heart Fail. 2014; 7: 470-478
        • Tadmouri A.
        • Blomkvist J.
        • Landais C.
        • Seymour J.
        • Azmoun A.
        Cost-effectiveness of left ventricular assist devices for patients with end-stage heart failure: analysis of the French hospital discharge database.
        ESC Heart Fail. 2018; 5: 75-86
        • Chew D.
        • Manns B.
        • Miller R.
        • Sharma N.
        • Exner D.
        Cost effectiveness of continuous flow left ventricular assist devices for destination therapy in end stage heart failure patients ineligible for cardiac transplantation.
        J Am Coll Cardiol. 2017; 33: 1283-1291
        • Baras Shreibati J.
        • Goldhaber-Fiebert J.D.
        • Banerjee D.
        • Owens D.K.
        • Hlatky M.A.
        Cost-effectiveness of left ventricular assist devices in ambulatory patients with advanced heart failure.
        JACC Heart Fail. 2017; 5: 110-119
        • Neyt M.
        • van den Bruel A.
        • Erasmus M.
        • et al.
        Cost-effectiveness of continuous-flow left ventricular assist devices.
        Int J Technol Assess Health Care. 2013; 29: 254-260
        • Mehra M.R.
        • Salerno C.
        • Cleveland J.C.
        • et al.
        Healthcare resource use and cost implications in the MOMENTUM 3 long-term outcome study randomized controlled trial of a magnetically levitated cardiac pump in advanced heart failure.
        Circulation. 2018; 138: 1923-1934
        • Health Quality Ontario
        Left ventricular assist devices for destination therapy: a health technology assessment.
        Ont Health Technol Assess Ser. 2017; 16: 1-60
        • Miller L.W.
        • Nelson K.E.
        • Bostic R.R.
        • et al.
        Hospital costs for left ventricular assist devices for destination therapy: lower costs for implantation in the post-REMATCH era.
        J Heart Lung Transplant. 2006; 25: 778-784
        • Murray M.A.
        • Osaki S.
        • Edwards N.M.
        • et al.
        Multidisciplinary approach decreases length of stay and reduces cost for ventricular assist device therapy.
        Interact Cardiovasc Thorac Surg. 2009; 8: 84-88
        • Shah N.
        • Garg J.
        • Martinez M.
        • et al.
        Impact of annual hospital volume on outcomes after left ventricular assist device (LVAD) implantation in the contemporary era.
        J Card Fail. 2016; 22: 232-237
      1. CorHealth Ontario. Recommendations to Support Ventricular Assist Device as Destination Therapy in Ontario.
        Comprehensive report. April 2019;