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Ann Thorac Surg 2000;70:1255-1258
© 2000 The Society of Thoracic Surgeons

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Original articles: cardiovascular

Recurrent remodeling after ventricular assistance: is long-term myocardial recovery attainable?

^a Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital–Columbia Campus, College of Physicians and Surgeons of Columbia University, New York, New York, USA
^b Division of Cardiology, Department of Medicine, New York Presbyterian Hospital–Columbia Campus, College of Physicians and Surgeons of Columbia University, New York, New York, USA

Address reprint requests to Dr Oz, Division of Cardiothoracic Surgery, New York Presbyterian Hospital, MHB 7-435, 177 Fort Washington Ave, New York, NY 10032
e-mail: mco2{at}columbia.edu

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. Long-term left ventricular assist devices (LVAD) have been used both as a bridge to heart transplantation and to recovery of native myocardial function. Despite much evidence for reversal of some of the structural and functional changes present in the failing heart during LVAD support, clinical evidence for sustained myocardial recovery is scant. We describe 2 patients in whom myocardial recovery during LVAD support led to device explanation only to have heart failure recur. This necessitated a second LVAD implantation, a process that we have termed recurrent remodeling.

Methods. The medical records of 2 patients with cardiomyopathy supported with HeartMate LVADs (Thermo Cardiosystems, Inc, Woburn, MA) were retrospectively reviewed.

Results. One patient was supported with an LVAD for 2 months, at which time the LVAD was explanted. Progressive deterioration of cardiac function followed, requiring a second LVAD 19 months after LVAD explanation. After 2 months of further LVAD support, a second episode of apparent myocardial recovery was observed during a period of device malfunction. The other patient was supported with an LVAD for 12 months, at which time the LVAD was explanted. The patient experienced progressive hemodynamic deterioration and required a second LVAD 6 months after LVAD explantation. Heart transplantations of both patients were successful.

Conclusions. Our understanding of myocardial recovery in the setting of hemodynamic unloading with LVAD support has not yet progressed to the point where we are able to accurately predict successful long-term LVAD explantation. The evolution of reliable predictors of sustainable myocardial recovery will help to avoid further cases of recurrent remodeling requiring repeat LVAD implantation.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
As the experience with long-term left ventricular assist device (LVAD) support has grown, reports have appeared of cases in which patients with left ventricular dysfunction treated with LVADs have unexpectedly experienced recovery of their myocardial function, allowing device explanation without immediate heart transplantation [1–3]. These device explantations were, in some cases, driven by factors related to device infection or malfunction as opposed to elective explantation procedures. The process by which hemodynamic unloading of the left ventricle with an LVAD leads to a reversal of the structural and functional abnormalities of the ventricle has been referred to as reverse remodeling [3]. Despite much evidence for reversal of some of the changes present in the failing heart, both at the level of the myocyte and in the structure and function of the ventricle, clinical evidence for sustained myocardial recovery is scant. There are no clear guidelines for the selection of patients for whom device explantation without transplantation is appropriate.

We describe 2 patients in whom myocardial recovery during LVAD support led to device explantation only to have heart failure recur, necessitating a second LVAD implantation, a process that we have termed recurrent remodeling. One of these patients went on to have a second episode of myocardial recovery during LVAD support with the second device.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
The medical records of 2 patients with cardiomyopathy treated at Columbia-Presbyterian Medical Center were reviewed retrospectively. Both patients underwent HeartMate LVAD (Thermo Cardiosystems, Inc, Woburn, MA) implantation using a previously reported technique [4]. Both pneumatic and vented-electric versions of the HeartMate LVAD were utilized.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Patient 1
A 30-year-old man presented to an outside hospital 7 months before LVAD implantation with a diffusely dilated, hypokinetic heart with a left ventricular ejection fraction (EF) of 15%. A diagnosis of idiopathic cardiomyopathy was made after a cardiac catheterization revealed normal coronary arteries and a myocardial biopsy sample showed areas of fibrosis. His medical regimen was optimized and he was discharged home with New York Heart Association class II heart failure. Five months later dyspnea, lower extremity edema, and ascites developed in the patient. In addition, atrial tachyarrhythmias developed, which persisted despite intravenous amiodarone, rapid pacing, and cardioversion. A transthoracic echocardiogram at this time showed an EF of 15% with a left ventricular end-diastolic diameter (LVEDD) of 7.0 cm. His hemodynamic condition progressively worsened and a pneumatic HeartMate LVAD was implanted.

Two months after the LVAD implantation, a suitable donor heart was identified and the patient was taken to the operating room for heart transplantation. With the patient heparinized and LVAD support discontinued under general anesthesia he was found to have a heart rate of 64, central venous pressure of 4 mm Hg, pulmonary artery pressure of 24/12 mm Hg, systemic blood pressure of 98/54 mm Hg, and a cardiac output of 6.0 L/min. A transesophageal echocardiogram (TEE) showed that the heart was not dilated and that the EF was normal without wall motion abnormalities without inotropic support. The LVAD was explanted without proceeding to subsequent heart transplantation.

The postoperative EF was 50% and the LVEDD was 5.3 cm. The patient’s cardiac function was followed with outpatient serial echocardiograms. Serial EF and LVEDD measurements are plotted in Figure 1.

View larger version (14K): [in this window] [in a new window]   Fig 1. (Patient 1.) Left ventricular end-diastolic diameter (LVEDD) and ejection fraction versus time after implantation of first left ventricular assist device (LVAD).

Two months after the second LVAD implantation the LVAD was noted to have been nonfunctioning for an unknown period of time. Intravenous heparin and dobutamine were started prophylactically. An echocardiogram revealed an EF of 35% to 40% and an LVEDD of 5.2 cm. The device was left in place but no attempt was made to restart the LVAD due to concerns of thromboembolism. The patient underwent heart transplantation 10 days later. Pathologic analysis of the native heart revealed diffuse myocyte hypertrophy and interstitial fibrosis consistent with idiopathic cardiomyopathy.

Patient 2
An 11-year-old girl was diagnosed with congestive heart failure (CHF) and was found to have an EF of 8% 3 months before LVAD implantation. Of note, her father died of cardiomyopathy at age 23 years and her paternal uncle died of cardiomyopathy at age 28 years. An endomyocardial biopsy sample was nonspecific and a diagnosis of familial cardiomyopathy was made. Hemodynamic instability prompted implantation of a vented-electric HeartMate LVAD. She made an uneventful recovery and was discharged home with the device in place.

Seven months after LVAD implantation, maximal treadmill exercise testing with hemodynamic monitoring with the LVAD rate lowered to 20 cycles/min revealed a peak VO₂ of 23.1 mL · kg^-1 · min^-1. Twelve months after LVAD implantation, the patient was readmitted with Pseudomonas sepsis and treated with intravenous antibiotics. An echocardiogram revealed an EF of 30% with an LVEDD of 5.0 cm with the LVAD output lowered to 2 L/min. Given her infected state and the apparent recovery of myocardial function, the LVAD was explanted. Left ventricular size and function were followed with serial echocardiograms as shown in Figure 2.

View larger version (13K): [in this window] [in a new window]   Fig 2. (Patient 2.) Left ventricular end-diastolic diameter (LVEDD) and ejection fraction versus time after implantation of first left ventricular assist device (LVAD).

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
Although LVADs have been utilized effectively as a bridge to a heart transplantation, their ability to provide sustainable recovery of myocardial function in patients with chronic heart failure is unclear. An important unresolved question remains as to whether any myocardial recovery observed during LVAD support will be maintained after LVAD explantation [3]. Long-term recovery will depend on whether significant changes have taken place in myocardial structure and function during LVAD support to reverse the underlying myocardial pathophysiologic process. Otherwise, any improvement in left ventricular function may be short-lived as the original disease process remains essentially unchanged.

In both of our reported cases the myocardial recovery that was observed in the operating room at the time of LVAD explantation was not sustained and both patients required a second LVAD implantation. In both cases the hearts were found to redilate with gradual reductions in ejection fraction over time. The clinical findings from these 2 patients, in addition to a case we reported previously, have demonstrated to us that in most cases reverse remodeling is itself reversible over time when the heart is reloaded [3]. It is interesting to note that patient 1 actually exhibited myocardial recovery with each of the two LVADs that supported him before his eventual heart transplantation. We do not know whether this second episode of recovery would have been sustained, but based upon the patient’s history and that of other cases, we felt it unlikely and proceeded with transplantation.

There are very few reports in the literature of cases in which LVADs have been explanted successfully without immediate heart transplantation with the exception of cases of acute viral myocarditis [5–8]. Despite the copious evidence for improvement in left ventricular dimensions and function during LVAD support, the clinical evidence for sustained recovery after device explantation without transplantation has been meager.

Mueller and associates [1] have reported a series of 17 patients with idiopathic cardiomyopathy who were supported for a mean of 230 days with LVADs. These authors were able to explant the devices in 5 of these patients without subsequent transplantation and reported that these patients had remained stable for up to 592 days. All those patients who could be successfully weaned and explanted had an LVEDD less than 7.5 cm before LVAD placement.

Our experience with LVAD explantation demonstrates that our understanding of myocardial recovery in the setting of hemodynamic unloading with assist devices has not yet progressed to the point where we are able to accurately predict successful long-term LVAD explantation. Two important questions remain. First, is there truly a subset of patients with chronic heart failure in whom mechanical support allows for sustained myocardial recovery? Second, if these patients do exist, how do we identify them as candidates for assist device explantation?

A number of markers of left ventricular recovery during LVAD support have been suggested (Table 1). The group at the Berlin Heart Institute has advised that the likelihood of myocardial recovery rises with early LVAD implantation before the development of fibrosis [9]. In addition, they have used the disappearance of anti-ß₁-adrenoreceptor antibodies as a marker of myocardial recovery [1]. Altemose and associates [10] have suggested that measurement of myocardial tissue atrial natriuretic peptide and brain natriuretic peptide levels could be used as an indicator of recovery. Mancini and colleagues [11] have evaluated exercise testing with simultaneous hemodynamic monitoring in LVAD patients and report that this may be useful in assessing myocardial recovery.

Our experience with LVAD explantation in 6 patients, out of approximately 170 LVAD implantations, indicates to us that the current state of knowledge about the sustainability of myocardial recovery is not fully developed and, thus, can make LVAD explantation unpredictable. We currently lack proven markers of irreversible reverse remodeling which can be utilized to select patients in whom LVAD explantation is appropriate. Patients with idiopathic dilated cardiomyopathy and acute ischemic syndromes, as opposed to chronic ischemic cardiomyopathies, are more likely to be those patients in whom recovery during mechanical support may be sufficient to allow LVAD explantation. Development of effective and reliable strategies for patient selection and weaning is necessary if we are to realize the potential benefits of LVAD support as a bridge to recovery and not just transplantation. The evolution of accurate predictors of enduring myocardial recovery will help to avoid further cases of recurrent remodeling after LVAD explantation.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

1. Mueller J., Wallukat G., Weng Y.G., et al. Weaning from mechanical cardiac support in patients with idiopathic dilated cardiomyopathy. Circulation 1997;96:542-549.[Abstract/Free Full Text]
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8. Reiss N., el-Banayosy A., Posival H., Morshuis M., Minami K., Korfer R. Management of acute fulminant myocarditis using circulatory support systems. Artif Organs 1996;20:964-970.[Medline]
9. Mueller J., Semrau S., Spiegelsberger S., et al. Therapy of end-stage idiopathic dilated cardiomyopathy by insertion of a monoventricular assist device. Artif Organs 1997;21:477.
10. Altemose G.T., Gritsus V., Jeevanandam V., Goldman B., Margulies K.B. Altered myocardial phenotype after mechanical support in human beings with advanced cardiomyopathy. J Heart Lung Transplant 1997;16:765-773.[Medline]
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