Ann Thorac Surg 2000;70:1690-1691
© 2000 The Society of Thoracic Surgeons
Case report
Normalization of native heart function years after heterotopic transplantation
Erik A.K. Beyer, MDa,
David Michael McMullan, MDa,
Reynolds Delgado, MDb,
Igor Gregoric, MDa,
Branislav Radovancevic, MDa,
O.H. Frazier, MDa
a Department of Cardiopulmonary Transplantation, Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, Texas, USA
b Department of Cardiology, University of Texas Medical School, Houston, Texas, USA
Address reprint requests to Dr Frazier, Texas Heart Institute, PO Box 20345, Houston, TX 77225-0345
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Abstract
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We describe a patient whose native heart function has normalized several years after heterotopic heart transplantation. The native heart sustained the patient’s circulation at a time when the donor heart was temporarily dysfunctional. Native heart improvement, let alone normalization, is considered rare after heterotopic transplantation but has been noted with increased frequency after long-term unloading with left ventricular assistance.
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Introduction
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In reporting the first heterotopic heart transplants performed in human beings, Barnard and Losman [1] described the donor heart’s potential role as a temporary assist device in patients with reversible heart failure. Since that time, the native heart has often been regarded as a "built-in assist device" that can provide circulatory support in the event of donor heart failure [2, 3]. As more experience has been gained with heterotopic heart transplants, some researchers have noted an improvement in native cardiac function after long-term unloading by the donor heart [3]. In at least one case involving explantation of a failed donor heart, the native heart’s function was found to have improved [4]. This finding reinforces the belief that long-term unloading of the failing heart may allow the organ to rest and recover its innate function by means of complex physiologic and biochemical processes [5, 6]. We describe a case in which, 9 years after heterotopic transplantation, the patient’s native heart is functioning normally.
In September 1988, a 53-year-old woman presented to our institution with severe congestive heart failure secondary to idiopathic cardiomyopathy. She had been treated for symptoms of congestive heart failure for 4 years. Upon admission to our hospital, she had a left ventricular ejection fraction (LVEF) of 12%, a pulmonary artery pressure of 70/45 mm Hg (mean 50 mm Hg), and a cardiac output of 2.25 L/min. Echocardiography showed a septal wall thickness of 0.9 cm, a left ventricular posterior wall (LVPW) thickness of 0.9 cm, left ventricular diastolic and systolic dimensions of 7.7 and 6.5 cm, respectively, and a left ventricular mass of 236 g. An endomyocardial biopsy showed myocyte hypertrophy and interstitial fibrosis.
In November 1988, a 26-year-old, 115-lb (52.3-kg) female heart donor was located. Heterotopic heart transplantation was performed, based on pulmonary hypertension and a greater than 20% mismatch between the recipient’s and the donor’s body weights. During the first 2 months after transplantation, the patient was readmitted for four separate rejection episodes (International Society for Heart and Lung Transplantation grade 3A; Texas Heart Institute grade 5), which were treated with pulsed steroids and intravenous cyclosporine. At the end of 2 months, right heart catheterization showed that the pulmonary artery pressure had decreased to 34/20 mm Hg (mean 24 mm Hg).
In September 1991, the patient returned for an annual checkup. Her medications included cyclosporine, prednisone, and metoprolol 200 mg daily for hypertension. Her native heart rate was 38 bpm, and her blood pressure was well controlled. Right heart catheterization again showed a reduced pulmonary artery pressure (range 36/20 mm Hg; mean 24 mm Hg). According to a radionuclide scan, the native heart function appeared to be improving, with a resting ejection fraction of 44%.
In 1996, 5 years after we first noted the native heart’s improvement, the heart continued to recover. In May 1996, two-dimensional echocardiography showed a native heart ejection fraction of 62% and a donor heart ejection fraction of only 15%. The native heart’s septal and posterior wall thickness had increased to 1.4 cm, the left ventricular diastolic dimension had decreased to 4.7 cm, and the left ventricular mass had increased to 261 g. Finally, in June 1997, echocardiography revealed a native heart ejection fraction of 60% and a donor heart ejection fraction of 45%. Coronary angiography showed no evidence of significant epicardial coronary artery disease in either heart. As of September 1999, 11 years after transplantation, the patient continues to live a full, active life.
In neither 1996 nor 1997 did donor heart biopsies reveal rejection. Morphologically, the native heart biopsy results obtained in 1996 did not differ appreciably from those obtained in 1988; both samples showed the same degree of cardiac myocyte hypertrophy, myocytolysis, interstitial and focal fibrosis, and focal endocardial fibrous thickening.
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Comment
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When Barnard and Losman [1] described the first heterotopic heart transplants performed in human beings, they regarded the donor heart as an "assist device" for the left ventricle. With the advent of mechanical assist devices, the myocardium’s ability to regain some function after long-term ventricular unloading was widely recognized [5, 6]. We have reported that prolonged unloading with a left ventricular assist device enhances myocardial function, improving the left ventricular end-diastolic dimensions and the ejection fraction [6, 7]. Others have noted that, with hemodynamic unloading of sufficient magnitude and duration, chamber enlargement may be reversed and positive ventricular remodeling achieved [5]. By allowing the heart to rest for prolonged periods, such unloading appears to improve left ventricular systolic function. In our case, prolonged ventricular unloading, perhaps combined with chronic ß blockade after heterotopic heart transplantation, resulted in normalization of native heart function.
Our patient’s native heart had a marked improvement in dimensions and ejection fraction (Fig 1). On follow-up examination in June 1997, the native heart’s ejection fraction was 60%. Right ventricular endomyocardial biopsy specimens failed to show significant native heart improvement, but evaluation of subendocardial tissue from the right ventricle may not be relevant for clarifying an improvement in left ventricular morphologic and functional parameters. As the donor heart declined in function, the native heart reassumed control over the patient’s circulation. The cause of donor heart deterioration in this case is not known. Coronary angiography and biopsy specimens did not indicate coronary artery disease or rejection, but small-vessel coronary artery disease is postulated to be the reason.
Interestingly, our patient was placed on ß-blocker therapy before her improved native heart function was discovered. At her follow-up visit in 1991, she had a native heart rate of 38 bpm and stable pulmonary artery pressures. In recent years, much research has been focused on the effects of neurohormonal activation on congestive heart failure. ß-Blockers and angiotensin-converting enzyme (ACE) inhibitors have been widely used in treating this condition. Both types of drugs have been shown to retard, and even reverse, systolic dysfunction by blunting the consequences of detrimental counter-regulatory effects in heart failure [8]. The mechanism by which ß-blockers exert their salutary effects is unknown, but theories include ß receptor modulation and change of fetal isoforms of myocytes to an adult form.
Although other experts [2] have observed a recovery of native heart function several months after heterotopic transplantation, such recovery is rare, and the native heart usually deteriorates progressively. In this setting, the mechanism for ventricular recovery is less clear than that associated with unloading and isolation of the heart by a left ventricular assist device. After heterotopic heart transplantation, the native heart must pump against high pressures generated by the donor heart, and cardiac "rest" is rarely achieved in a parallel heart model. Our case is unique in that our patient’s native heart did not begin to improve until 3 years after transplantation and then continued to improve until its normal status was regained. The reason for this recovery is still unclear. Nevertheless, this case may help further the understanding of the dynamics of the failing heart and the benefits of chronic unloading.
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References
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Barnard C.N., Losman J.G. Left ventricular bypass. S Afr Med J 1975;49:303-312.[Medline]
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Cooper D.K.C. Advantages and disadvantages of heterotopic transplantation. In: Cooper D.K.C., Lanza R.P., eds. Heart transplantation. Lancaster, UK: MTP Press, 1984:305-319.
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Nakatani T., Frazier O.H., Lammermeier D.E., et al. Heterotopic heart transplantation. A reliable option for a select group of high-risk patients. J Heart Transplant 1989;8:40-46.[Medline]
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Konertz W., Sheikzadeh A., Weyand M., et al. Heterotopic heart transplantation. Tex Heart Inst J 1988;15:159-162.
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Levin H.R., Oz M.C., Chen J.M., et al. Reversal of chronic ventricular dilation in patients with end-stage cardiomyopathy by prolonged mechanical unloading. Circulation 1995;91:2717-2720.[Abstract/Free Full Text]
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Frazier O.H., Benedict C.R., Radovancevic B., et al. Improved left ventricular function after chronic left ventricular unloading. Ann Thorac Surg 1996;62:1-7.[Abstract/Free Full Text]
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Frazier O.H. First use of an untethered, vented electric left ventricular assist device for long-term support. Circulation 1994;89:2908-2914.[Abstract/Free Full Text]
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Eichhorn E.J., Bristow M.R. Medical therapy can improve the biological properties of the chronically failing heart. Circulation 1996;94:2285-2296.[Abstract/Free Full Text]
Accepted for publication January 11, 2000.
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Invited commentary
- Irving L. Kron
Ann. Thorac. Surg. 2000 70: 1691-1692.
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Abstract
Introduction
