Left Ventricular Assist Device and Drug Therapy for the Reversal of Heart Failure
Emma J. Birks, M.R.C.P., Ph.D., Patrick D. Tansley, F.R.C.S., James Hardy, M.B., B.S., B.Sc., Robert S. George, M.R.C.S., B.Sc., Christopher T. Bowles, Ph.D., Margaret Burke, F.R.C.Path., Nicholas R. Banner, F.R.C.P., Asghar Khaghani, F.R.C.S., and Magdi H. Yacoub, F.R.S.
Background In patients with severe heart failure, prolongedunloading of the myocardium with the use of a left ventricularassist device has been reported to lead to myocardial recoveryin small numbers of patients for varying periods of time. Increasingthe frequency and durability of myocardial recovery could reduceor postpone the need for subsequent heart transplantation.
Methods We enrolled 15 patients with severe heart failure dueto nonischemic cardiomyopathy and with no histologic evidenceof active myocarditis. All had markedly reduced cardiac outputand were receiving inotropes. The patients underwent implantationof left ventricular assist devices and were treated with lisinopril,carvedilol, spironolactone, and losartan to enhance reverseremodeling. Once regression of left ventricular enlargementhad been achieved, the 2-adrenergicreceptor agonist clenbuterolwas administered to prevent myocardial atrophy.
Results Eleven of the 15 patients had sufficient myocardialrecovery to undergo explantation of the left ventricular assistdevice a mean (±SD) of 320±186 days after implantationof the device. One patient died of intractable arrhythmias 24hours after explantation; another died of carcinoma of the lung27 months after explantation. The cumulative rate of freedomfrom recurrent heart failure among the surviving patients was100% and 88.9% 1 and 4 years after explantation, respectively.The quality of life as assessed by the Minnesota Living withHeart Failure Questionnaire score at 3 years was nearly normal.Fifty-nine months after explantation, the mean left ventricularejection fraction was 64±12%, the mean left ventricularend-diastolic diameter was 59.4±12.1 mm, the mean leftventricular end-systolic diameter was 42.5±13.2 mm, andthe mean maximal oxygen uptake with exercise was 26.3±6.0ml per kilogram of body weight per minute.
Conclusions In this single-center study, we found that sustainedreversal of severe heart failure secondary to nonischemic cardiomyopathycould be achieved in selected patients with the use of a leftventricular assist device and a specific pharmacologic regimen.
Source Information
From the Royal Brompton and Harefield National Health Service Trust, Harefield, Middlesex, United Kingdom (E.J.B., P.D.T., J.H., R.S.G., C.T.B., M.B., N.R.B., A.K., M.H.Y.); and the Heart Science Centre, National Heart and Lung Institute, Imperial College, London (E.J.B., P.D.T., J.H., R.S.G., C.T.B., A.K., M.H.Y.).
Address reprint requests to Dr. Yacoub at the Heart Science Centre, Royal Brompton and Harefield Hospital, Harefield, Middlesex UB9 6JH, United Kingdom, or at m.yacoub{at}ic.ac.uk.
Klotz, S., Burkhoff, D., Garrelds, I. M., Boomsma, F., Danser, A.H.J.
(2009). The impact of left ventricular assist device-induced left ventricular unloading on the myocardial renin-angiotensin-aldosterone system: therapeutic consequences?. Eur Heart J
30: 805-812
[Abstract][Full Text]
Brinks, H., Tevaearai, H., Muhlfeld, C., Bertschi, D., Gahl, B., Carrel, T., Giraud, M.-N.
(2009). Contractile function is preserved in unloaded hearts despite atrophic remodeling.. J. Thorac. Cardiovasc. Surg.
137: 742-746
[Abstract][Full Text]
Leontiadis, E., Morshuis, M., Arusoglu, L., Cobaugh, D., Koerfer, R., El-Banayosy, A.
(2008). Thoratec Left Ventricular Assist Device Removal After Toxic Myocarditis. Ann. Thorac. Surg.
86: 1982-1985
[Abstract][Full Text]
Takeda, K., Matsumiya, G., Matsue, H., Hamada, S., Fujita, T., Sawa, Y.
(2008). Noninvasive assessment of cardiac function during ventricular assist system support using 64-row multidetector computed tomographic angiography.. J. Thorac. Cardiovasc. Surg.
136: 1602-1603
[Full Text]
Lara-Pezzi, E., Felkin, L. E., Birks, E. J., Sarathchandra, P., Panse, K. D., George, R., Hall, J. L., Yacoub, M. H., Rosenthal, N., Barton, P. J. R.
(2008). Expression of Follistatin-Related Genes Is Altered in Heart Failure. Endocrinology
149: 5822-5827
[Abstract][Full Text]
Siedlecka, U., Arora, M., Kolettis, T., Soppa, G. K. R., Lee, J., Stagg, M. A., Harding, S. E., Yacoub, M. H., Terracciano, C. M. N.
(2008). Effects of clenbuterol on contractility and Ca2+ homeostasis of isolated rat ventricular myocytes. Am. J. Physiol. Heart Circ. Physiol.
295: H1917-H1926
[Abstract][Full Text]
Qanud, K., Mamdani, M., Pepe, M., Khairallah, R. J., Gravel, J., Lei, B., Gupte, S. A., Sharov, V. G., Sabbah, H. N., Stanley, W. C., Recchia, F. A.
(2008). Reverse changes in cardiac substrate oxidation in dogs recovering from heart failure. Am. J. Physiol. Heart Circ. Physiol.
295: H2098-H2105
[Abstract][Full Text]
Loisance, D.
(2008). Mechanical Circulatory Support: a Clinical Reality. Asian Cardiovasc. Thorac. Ann.
16: 419-431
[Abstract][Full Text]
Dandel, M., Weng, Y., Siniawski, H., Potapov, E., Drews, T., Lehmkuhl, H. B., Knosalla, C., Hetzer, R.
(2008). Prediction of Cardiac Stability After Weaning From Left Ventricular Assist Devices in Patients With Idiopathic Dilated Cardiomyopathy. Circulation
118: S94-S105
[Abstract][Full Text]
Moore, D, Anderson, M, Larson, D.
(2008). Effect of clenbuterol administration on the healthy murine heart. Perfusion
23: 297-302
[Abstract]
Raake, P. W., Vinge, L. E., Gao, E., Boucher, M., Rengo, G., Chen, X., DeGeorge, B. R. Jr, Matkovich, S., Houser, S. R., Most, P., Eckhart, A. D., Dorn, G. W. II, Koch, W. J.
(2008). G Protein-Coupled Receptor Kinase 2 Ablation in Cardiac Myocytes Before or After Myocardial Infarction Prevents Heart Failure. Circ. Res.
103: 413-422
[Abstract][Full Text]
Braunwald, E.
(2008). The Management of Heart Failure: The Past, the Present, and the Future. Circ Heart Fail
1: 58-62
[Full Text]
Lynch, G. S., Ryall, J. G.
(2008). Role of {beta}-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease. Physiol. Rev.
88: 729-767
[Abstract][Full Text]
Soppa, G. K.R., Lee, J., Stagg, M. A., Felkin, L. E., Barton, P. J.R., Siedlecka, U., Youssef, S., Yacoub, M. H., Terracciano, C. M.N.
(2008). Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure. Cardiovasc Res
77: 695-706
[Abstract][Full Text]
Haj-Yahia, S., Birks, E.J., Dreyfus, G., Khaghani, A.
(2008). Limited surgical approach for explanting the HeartMate II left ventricular assist device after myocardial recovery.. J. Thorac. Cardiovasc. Surg.
135: 453-454
[Full Text]
Kooshkabadi, M., Kalogeropoulos, A., Babaliaros, V. C., Lerakis, S.
(2008). Transesophageal guided left atrial positioning of a percutaneous ventricular assist device. Eur J Echocardiogr
9: 175-177
[Abstract][Full Text]
Davies, R. R.
(2007). Invited commentary. Ann. Thorac. Surg.
84: 1262-1263
[Full Text]
Shuros, A. C., Salo, R. W., Florea, V. G., Pastore, J., Kuskowski, M. A., Chandrashekhar, Y., Anand, I. S.
(2007). Ventricular Preexcitation Modulates Strain and Attenuates Cardiac Remodeling in a Swine Model of Myocardial Infarction. Circulation
116: 1162-1169
[Abstract][Full Text]
Mau, J., Menzie, S., Ward, M., Bundgaard, H., Hunyor, S.
(2007). Time-dependent response of both ventricles after septal ablation: Implications for biventricular support after left ventricular assist device placement. J. Thorac. Cardiovasc. Surg.
134: 579-586
[Abstract][Full Text]
Hunt, S. A.
(2007). Mechanical Circulatory Support: New Data, Old Problems. Circulation
116: 461-462
[Full Text]
Haykowsky, M. J., Liang, Y., Pechter, D., Jones, L. W., McAlister, F. A., Clark, A. M.
(2007). 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
49: 2329-2336
[Abstract][Full Text]
Maybaum, S., Mancini, D., Xydas, S., Starling, R. C., Aaronson, K., Pagani, F. D., Miller, L. W., Margulies, K., McRee, S., Frazier, O.H., Torre-Amione, G., for the LVAD Working Group,
(2007). Cardiac Improvement During Mechanical Circulatory Support: A Prospective Multicenter Study of the LVAD Working Group. Circulation
115: 2497-2505
[Abstract][Full Text]
Jones, R. H.
(2007). The Year in Cardiovascular Surgery. J Am Coll Cardiol
49: 1887-1898
[Full Text]
Milbrandt, E. B., Ishizaka, A., Angus, D. C.
(2007). Update in Critical Care 2006. Am. J. Respir. Crit. Care Med.
175: 638-648
[Full Text]
Hall, J. L., Birks, E. J., Grindle, S., Cullen, M. E., Barton, P. J., Rider, J. E., Lee, S., Harwalker, S., Mariash, A., Adhikari, N., Charles, N. J., Felkin, L. E., Polster, S., George, R. S., Miller, L. W., Yacoub, M. H.
(2007). Molecular signature of recovery following combination left ventricular assist device (LVAD) support and pharmacologic therapy. Eur Heart J
28: 613-627
[Abstract][Full Text]
Lowes, B. D., Baker, M. L., Blaxall, B. C.
(2007). Gene expression profile of the recovering human heart. Eur Heart J
28: 522-524
[Full Text]
Lindsay, A.
(2007). JournalScan. Heart
93: 409-410
[Full Text]
Hetzer, R., Dandel, M., Knosalla, C., Burniston, J. G., Florea, V. G., Rott, D., Leibowitz, D., Vanderwilt, G. J., Yacoub, M. H., Birks, E. J.
(2007). Left Ventricular Assist Devices and Drug Therapy in Heart Failure. NEJM
356: 869-872
[Full Text]
(2006). End stage heart failure may be reversible. BMJ
333: 1014-1014
[Full Text]
Renlund, D. G., Kfoury, A. G.
(2006). When the Failing, End-Stage Heart Is Not End-Stage. NEJM
355: 1922-1925
[Full Text]
(2006). Can an LVAD plus Drugs Reverse Advanced Systolic Heart Failure?. Journal Watch Cardiology
2006: 2-2
[Full Text]