Eur J Cardiothorac Surg 1999;15:20-25
© 1999 Elsevier Science NL
Left ventricular assist device as a bridge to partial left ventriculectomy 1
O.H Frazier*
Texas Heart Institute, P.O. Box 20345, MC 3-147, Houston, TX 77225-0345, USA
* Tel.: +1-713-791-3000; fax: +1-713-794-6798.
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Abstract
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In 1963, Dr Michael DeBakey successfully implanted the first left ventricular assist device. Throughout the 1970s, cardiovascular research aimed to achieve long-term circulatory support with such devices; later, as improved medical therapy decreased patients' chances of organ rejection or infection, transplantation became a viable alternative for the treatment of heart failure. At that point, left ventricular assist devices began to be used as bridges to transplantation. As left ventricular assist devices were used for longer periods of time, we realized that the ventricular function and overall health of the patients awaiting transplant improved. Used as a bridge to transplantation, left ventricular assist devices often increased a patient's chances of survival and recovery. Recently left ventricular assist devices have been used as bridges to partial left ventriculectomy (the Batista procedure). Our early experiences with this procedure in selected patients have been promising. Many patients recover to NYHA functional class I after prolonged left ventricular unloading, surgery, or both. In addition, the native heart may be saved, especially in younger patients, eliminating the need for transplantations and decreasing the strain on the limited organ donor pool.
Key Words: Left ventricular assist device • Ventriculectomy • Transplantation • Congestive heart failure
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Introduction
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For many years, the standard therapy for heart failure was simply bed rest. In 1963, however, a major breakthrough occurred in the treatment of heart failure: Dr Michael DeBakey implanted a left ventricular assist device, or LVAD, into a patient with severe heart failure. The LVAD was designed to allow the ventricle to rest and recover [1]. When funding from the National Institutes of Health became available in the 1970s, most research on the treatment of heart failure aimed to achieve long-term circulatory support because neither transplanted nor total artificial hearts were considered viable. With the advent of better immunosuppressive drugs like cyclosporine in the 1980s, however, transplantation regained acceptance in clinical practice. By using a mechanical circulatory support device as a bridge to transplantation, surgeons could help even patients who had undergone previous cardiac operations. The precedent for use of such devices had already been set – by Dr DeBakey in 1963; by Dr Denton Cooley [2]in 1969 with a total artificial heart; by Dr John Norman [3]in 1976 with an LVAD; and by Drs Tetsuzo Akutzu and Cooley [4]in 1981 with an artificial heart.
Most recently, the LVAD has been used as a bridge to partial left ventriculectomy (the Batista procedure). Our studies indicate that this procedure may reduce the strain on cardiomyopathic hearts and improve heart function in selected patients.
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1. Ventricular unloading: rest and recovery
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1.1 Bed rest
In the 1950s, Dr George Burch advocated bed rest as a therapy for heart failure. Burch received a grant from the Public Health Service to study whether patients with chronic heart failure would improve after a regimen of long-term bed rest (greater than 3 months). His protocol was elaborate, and in many cases, his patients improved [5]One man with severe, chronic heart failure who rested for approximately 80 days was eventually able to return to work, but unfortunately his symptoms returned. He was prescribed bed rest again, and he remained alive 8.5 years later.
Most dissenters believe that Dr Burch's patients suffered from alcoholic cardiomyopathy, a condition that is not representative of today's patients. While some patients had alcohol-induced myopathy, Dr Burch identified 31 patients in his study who clearly had idiopathic myopathies; of those patients, ten recovered normal heart function after bed rest (Table 1
) [5]. One of the characteristics of these ten patients was a shorter duration of heart failure before bed rest (mean 14 months). Research has now shown that integrity of the extracellular matrix and stiffening of the heart may be important keys to recovery from idiopathic cardiomyopathy [6, 7]. This could help explain why patients with a shorter duration of heart failure improved the most in Dr Burch's results.
1.2 Mechanical ventricular unloading
At the Texas Heart Institute, we have been involved in LVAD research since the early 1970s. We currently use the HeartMateTM LVAD (Thermo Cardiosystems, Woburn, MA) (Fig. 1
) for chronic support. The shortage of donor hearts compelled us to develop alternative treatments for patients with heart failure and led to our early extended use of LVADs. We found that patients, particularly those who were large and had blood type O, could live with the devices for long periods of time. These are the patients who typically wait the longest for a donor heart (Table 2
). With the LVAD, they usually recovered to New York Heart Association (NYHA) functional class I; by the time donor hearts were available, their overall condition was significantly improved, making them better transplant candidates and more likely to survive [8]. The device worked so well that we have now received approval from the Food and Drug Administration (FDA) to discharge patients from the hospital with electrically driven LVADs still implanted.
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Table 2. UNOS analysis of heart waiting list registrations and median waiting time until transplantation for the entire US
a
(patients<200 lb)
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The first such patient left the hospital in November 1991. In my last conversation with him, he said, `Why don't we just take out this pump? I think my heart is better now and I'll be all right without it.' At that time, however, the FDA did not allow removal of the pump. In January 1993, this patient felt so well that he stopped taking Coumadin; 8 days later, he suffered a massive stroke that proved fatal. Before he died, we determined that his left ventricular end-diastolic dimension had, for the most part, corrected itself; it decreased from 8.5 to 5.5 cm after LVAD implantation (Fig. 2
). His stroke volume had also markedly improved (from 20 to 54 cc), although his ejection fraction was still abnormal (15%, up from 8%). This is the first report of a patient undergoing myocardial recovery with prolonged left ventricular unloading (305 days) [9].
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Fig. 2. Roentgenograms taken before LVAD implantation (left) and 180 days after LVAD implantation (right). Note the significantly decreased cardiac silhouette.
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Prompted by this case and other patients in whom we saw similar improvements, we retrospectively analyzed data from 31 patients (30 men, 1 woman) with chronic heart failure (33.5±39 months) to assess their degree of ventricular recovery [6]. Their mean age was 48 years (range 22–64 years). Seventeen patients had idiopathic cardiomyopathy and 14 had ischemic cardiomyopathy. Our assessment included physiologic, hemodynamic, histologic, biochemical and gross anatomic measurements. Data were collected at three intervals: at implantation; during the period of support with the device off; and at explantation (mean 137 days; range 31 to 505 days). The LVAD allows much more profound ventricular unloading than if the patient were confined to bed but permits full mobility of the patient. Thus, we were able to study an effect of rest similar to that reported by Dr Burch. Also, because implantation of an LVAD requires that a large segment of myocardium be cored from the apex of the ventricle (Fig. 3
), we could easily study the histology, ultrastructure, and calcium and glucose metabolism of the excised tissue.
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Fig. 3. Technique used to core a section of the left ventricle for implantation of the inlet graft to the LVAD.
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All of the histologic characteristics of heart failure could be seen in these 31 patients: stretching of the fibers, expansion of the collagen matrix, and boxed nuclei (Fig. 4
). After implantation of the LVAD, heart function consistently improved (Fig. 5
). Severe myocytolysis, which was evident before treatment in one of our patients (Fig. 6
), almost disappeared after 8 months of LVAD support (Fig. 7
). Other physiologic measurements also improved in the patients after LVAD implantation (Table 3
). End-diastolic dimensions of all 31 patients were assessed by echocardiography at varying times while the LVAD was off; in all cases, heart size decreased. The ejection fractions doubled, and pulmonary capillary wedge pressure decreased. Peripheral vascular resistance improved, and myocytolysis was markedly improved at the time of transplantation compared to that seen at the time of LVAD implantation [6].
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Fig. 4. Longitudinal section of heart muscle before LVAD implantation, showing stretching of myocardial fibers, expansion of the collagen matrix, and boxed nuclei.
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Fig. 5. Longitudinal section of heart muscle in the same patient as in Fig. 4 38 days after LVAD implantation, showing improved myocardial geometry.
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Fig. 7. Longitudinal section of heart muscle in the same patient as in Fig. 6 after 8 months of LVAD support. Note near normalization of the cellular matrix.
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To investigate the effect of the LVAD on ventricular function, we examined subcellular organelles and membrane proteins in cardiac tissue taken before and after LVAD implantation. Because many researchers now believe that the inability to regulate calcium flux is an early manifestation of heart failure in idiopathic cardiomyopathy, [6, 10]we measured calcium flux in 12 patients to determine oxalate-facilitated calcium uptake in the sarcoplasmic reticulum before and after LVAD implantation (Fig. 8
). In the specimens before LVAD implant, calcium uptake was markedly deranged, whereas it invariably normalized in the postoperative specimens. At the time of transplantation, we observed near-normalization of the calcium-binding ability of the sarcoplasmic reticulum, an essential component of normal heart function (Fig. 9
). In addition, phospholipid levels demonstrated the positive effects of LVADs on ventricular function (Table 4
). Lysozymes that destroy the membrane are very active in the preoperative specimen but become much less active after LVAD implantation. We also found that deranged norepinephrine levels generally decrease after LVAD implantation; our results collaborated with those reported by the Cleveland Clinic [11]. All indicators of ventricular function improved following prolonged unloading of the heart.
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Fig. 8. Oxalate-facilitated calcium uptake in the sarcoplasmic reticulum before and after LVAD implantation. The markedly deranged preoperative specimens returned to normal postoperatively.
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Fig. 9. Calcium-binding ability of the sarcoplasmic reticulum, which was almost normal at the time of transplantation.
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2. LVAD as a bridge to partial left ventriculectomy (the Batista procedure)
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New questions then arose: could the LVAD be used as a bridge to partial ventriculectomy in patients who would otherwise need a heart transplant to survive? Would cardiac function recover enough after chronic ventricular unloading to allow for LVAD removal? Several of our first cases indicate that the answer to both questions is yes.
Our first patient was a large man, approximately 6'6'' and 240 lb. In May 1995, he received an electrical LVAD. One month later he was discharged from the hospital to await transplant. One year later he was readmitted in heart failure, despite maximal medical therapy. A chest roentgenogram showed that his heart size had increased, approximating the size of his heart at the time of LVAD implantation. Our studies revealed that valvular insufficiency had developed in the pump, which caused his heart to redilate. At that time, we decided to remove the LVAD and perform a partial left ventriculectomy (PLV).
Immediately after the operation, the patient's heart function dramatically improved. Only Nipride was needed to keep his pressure down. Although the diameter of the ventricle was still larger than normal, it was much improved. At follow-up 1 year later, the patient was in NYHA class I and had returned to work. He remains well without any mechanical support, taking only standard cardiac medications. Although his heart function is still abnormal, he is certainly in better health than he would have been with either an LVAD or a transplanted heart. Because of his size, it was unlikely that we would ever have found a suitable donor heart for him.
Another of our early cases also demonstrates the potential of the ventriculectomy procedure. A 24-year-old woman from the United Arab Emirates was transferred to our institution in March 1996. She had severe heart failure caused by idiopathic cardiomyopathy and a methicillin-resistant Staphylococcus infection. After 156 days of LVAD support, her cardiac index had improved from 1.2 to 2.7 l/min per m2, and we performed a ventriculectomy. One year later, she was in NYHA class I.
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3. Comment
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The mortality associated with heart transplantation is approximately 6% per year over 5 years; however, 15% of transplant patients do not survive the first year [12]. Only about 2300 transplants are performed each year in the United States, and this number has not increased since 1993 [12]. In addition, patients who undergo heart transplants die prematurely. While older patients may be happy to live 5–10 more years, most young adults want more permanent results. This younger group of patients will benefit most from LVAD technology, possibly in combination with PLV. Today, I would consider PLV for any young adult with an idiopathic cardiomyopathy. When the Batista procedure is successful, heart transplantation and its attendant complications, including premature death, may be postponed or avoided altogether.
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Conference discussion
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Mr S. Westaby
(Oxford, UK): I think the issue of mechanical bridge to myocyte recovery is potentially the most exciting development in the treatment of heart failure in the last 15 years.
Audience
: Congratulations on your fine results. A few years ago, Lynne W. Stevenson stated that the survival benefit from heart transplantation is small for patients waiting on the list more than 6 months. She suggested reevaluating all patients who have been waiting for more than 6 months and reserving heart transplantations for only the critically ill patients. Do you think that would present an opportunity to begin using these alternative surgical options in those patients?
Dr O.H. Frazier
: In general, we reserved the LVAD for patients who fit the FDA criterion for insertion, which was severe heart failure. Supported by an assist device, these patients are not so sick when they eventually undergo transplantation and, thus, they have better outcomes. I am aware of Dr Stevenson's work, but one of the problems with heart transplantation is that there has never been a randomized study of its benefits. It is unclear which of the class II and III outpatients will benefit from recent improvements in medical therapy, so I would be reluctant to embark on any surgical procedure for such patients.
Mr S. Westaby
: The problem with the current treatment of alleged end-stage heart failure is that the patient becomes desperately sick while waiting for a donor organ, often experiencing multiorgan failure. If you had both permission and a user-friendly LVAD, such as Dr Jarvik's impeller pump (the Jarvik 2000), would you consider intervening at perhaps the class II and certainly the class III level to prevent end-stage heart failure? Do you think the device, implanted at that stage, could prevent heart failure altogether in some dilated cardiomyopathies?
Dr O.H. Frazier
: I think so. I hope that will be its clinical use. As Dr Burch discovered, patients with shorter-duration heart failure are the most likely to improve. Although we will eventually better understand the extracellular matrix and thickening of collagen that characterize chronic heart failure, it is unlikely that we will be able to cure the condition. It is important to intervene at an earlier stage to improve the chance of recovery. I think that within the next 2–5 years, the therapy for some younger patients with idiopathic cardiomyopathies may well be surgical intervention with PLV or an LVAD as an initial therapy, not transplantation.
Mr S. Westaby
: Children with viral myocarditis who underwent cardiac massage and were supported with an external LVAD are also fascinating. They have returned to complete normality. It would be an enormous advance even if we only treated children with viral myocarditis in end-stage heart disease with the small LVADs.
Dr G. Tolis
(Athens, Greece): Are you then suggesting that every patient who is a candidate for PLV today should have the LVAD first, in the hope that he may not need PLV?
Dr O.H. Frazier
: No, I think most patients with severe heart failure will need PLV, because in many cases the ventricle will still be enlarged. I have described what I am doing, although I understand that the technologies available to me are not available everywhere. I hope they will be, however, particularly the continuous-flow pump [13]. This pump will be a tremendous advance in the field of mechanical circulatory support. It is small (about the size of a thumb), and we have been able to implant it in animals without using cardiopulmonary bypass. It can be made very inexpensively and should have far wider indications. I do believe that LVADs should be considered before a heart transplantation in young patients with idiopathic cardiomyopathies, because if you can spare these patients a transplantation, you have done them a great service.
Mr S. Westaby
: At this point, the Jarvik 2000 can be implanted without cardiopulmonary bypass, and we have electively explanted the device from sheep on three occasions to prove the possibility of a mechanical bridge to recovery. It is an easy procedure, and the animals return to the fields.
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Footnotes
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1 Presented at the Sulzer Carbomedics Sixth International Clinical Symposium, Copenhagen, Denmark, 27 September 1997. 
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References
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- DeBakey ME. Left ventricular bypass pump for cardiac assistance: clinical experience. Am J Cardiol 1971;27:3-11.[Medline]
- Cooley DA, Liotta D, Hallman GL, Bloodwell RD, Leachman RD, Milam JD. Orthotopic cardiac prosthesis for two-staged cardiac replacement. Am J Cardiol 1969;24:723-730.[Medline]
- Norman JC, Brook MI, Cooley DA, Klima T, Kahan BD, Frazier OH, Keats AS, Hacker J, Massin EK, Duncan JM, Solis RT, Dacso CC, Luper WE, Winston DS, Reul GJ. Total support of the circulation of a patient with postcardiotomy stone heart syndrome by a partial artificial heart (ALVAD) for 5 days followed by heart and kidney transplantation. Lancet 1978;1:1125-1127.[Medline]
- Cooley DA, Akutzu T, Norman JC, Serrato MA, Frazier OH. Total artificial heart in two staged cardiac transplantation. Cardiovasc Dis Bull Texas Heart Inst 1981;8:305-319.
- McDonald CD, Burch GE, Walsh JJ. Prolonged bed rest in the treatment of idiopathic cardiomyopathy. Am J Med 1972;52:41-50.[Medline]
- Frazier OH, Benedict CR, Radovancevic B, Bick RJ, Capek P, Springer WE, Macris MP, Delgado R, Buja LM. Improved left ventricular function after chronic left ventricular unloading. Ann Thorac Surg 1996;62:675-682.[Abstract/Free Full Text]
- Factor SM. Role of the extracellular matrix in dilated cardiomyopathy. Heart Failure 1993;9:260-267.
- Frazier OH, Rose EA, McCarthy P, Burton NA, Tector A, Levin H, Kayne HL, Poirier VL, Dasse KA. Improved mortality and rehabilitation of transplant candidates treated with a long-term implantable left ventricular assist system. Ann Surg 1995;222:327-338.[Medline]
- Frazier OH. First use of an untethered, vented electric left ventricular assist device for long-term support. Circulation 1994;89:2908-2914.[Abstract/Free Full Text]
- Parameshwar J, Poole-Wilson PA. The role of calcium antagonists in the treatment of chronic heart failure. Eur Heart J 1993;14(Suppl A):38-44.
- James, K.B., McCarthy, P.M., Thomas, J.D., Vargo, R., Hobbs, R.E., Sapp, S., Bravo, E. Effect of the implantable left ventricular assist device on neuroendocrine activation in heart failure. Circulation 1995;92(Suppl 9):II191–II195..
- United Network for Organ Sharing Web site. Annual Report of the US Scientific Registry for Organ Transplantation and the Organ Procurement and Transplantation Network, 1997. Available at: http://www.unos.org/frame_Default.asp?Category=DataAR97. Accessed June 24, 1998..
- Macris MP, Myers TJ, Jarvik R, Robinson JL, Fuqua JM, Parnis SM, Frazier OH. In vivo evaluation of an intraventricular electric axial flow pump for left ventricular assistance. ASAIO J 1994;40:M719-M722.[Medline]
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Abstract
Introduction
