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Ann Thorac Surg 2001;71:S109-S113
© 2001 The Society of Thoracic Surgeons

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Session 2: bridging to transplant and alternatives to transplant

Bridging-to-recovery

^a Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum, Berlin, Berlin, Germany

Address reprint requests to Dr Hetzer, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
e-mail: hetzer{at}dhzb.de

Presented at the Fifth International Conference on Circulatory Support Devices for Severe Cardiac Failure, New York, NY, Sept 15–17, 2000.

Abstract

Background. Patients with end-stage heart failure placed on a cardiac assist device show at least some degree of improvement of cardiac function. In a subgroup of selected patients, some hearts recovered considerable function. In these patients the device was removed and cardiac transplantation was no longer necessary. We report our long-term experience with these weaned patients.

Methods. As of today, 512 cardiac assist devices of various types (Berlin Heart, Berlin, Germany; Novacor, World Heart, Ottawa, Ontario, Canada; TCI, ThermoCardio Systems, Inc, Woburn, MA; DeBakey, Micromed Technology Inc, Houston, TX) were implanted in patients with end-stage heart failure in our institution. Of these, 95 patients belonged to a subgroup of patients with nonischemic, idiopathic, dilated cardiomyopathy who were implanted with a left ventricular support system (Novacor 84, TCI 10, Berlin Heart 1) between 1994 and 2000. All were routinely examined by echocardiography for improvement of cardiac function. The left ventricular diameter in diastole (LVIDd) and left ventricular ejection fraction (LVEF) served as the main parameters to assess changes in cardiac performance. Under the conditions of a running device, an LVIDd below 60 mm and an LVEF above 40% were the criteria to do further echocardiographic studies when the pump was turned off for up to 20 minutes.

Results. Twenty-eight patients (26 men, 2 women; ages 18 to 64 yrs; history of heart failure, 1 to 17 yrs) fulfilled the criteria of improved cardiac performance and were weaned from the device. Since then, 16 patients have continued "normal" heart function with follow-up times ranging from 1 month to 5.5 years (group B). Three patients died of noncardiac causes (group C). Eight patients were transplanted from 1 to 17 months later and one died on the waiting list (group A). Statistically significant differences between groups A and B were calculated for the duration of heart failure (9 versus 2 years, p = 0.0002). Differences in LVIDd before removal of the device (57 versus 51 mm, p = 0.0420), LVEF after 2 months of unloading (30 versus 49%, p = 0.0300), and LVEF preexplantation (43 versus 52%, p = 0.0001) were significant. Overall, 17% of the cohort of 95 patients were weaned successfully.

Conclusions. Weaning from cardiac assist devices is feasible for selected patients; it saves donor hearts and is preferred to cardiac transplantation. However, as of today no reliable parameter predicts outcome after weaning and none determines the possibility of device removal before implantation in advance.

Since our first observation that patients with end-stage idiopathic dilated cardiomyopathy (IDC) treated with a left ventricular cardiac assist device (LVAD) may demonstrate restoration of heart function, (which may be sustained long-term after device explanation), removal of the device without transplantation has attracted considerable interest in the heart failure research community and a number of clinical reports have been published [1–7]. Meanwhile, our experience with this concept, which is based on more patients, longer follow-up, and more detailed investigations has widened. However, the most important clinical questions continue to await definite answers, namely:

1. Which cases of IDC are amenable to recovery by mechanical unloading?
   
2. Which criteria indiate complete and long-term cardiac recovery on the assist device?
   
3. What is the ideal time to remove the device once recovery appears to have occurred?
   

On the basis of the investigations performed during unloading and after assist explantation, we have reached a somewhat better understanding of the recovery process and, thus, a more reliable decision-making basis.

Patients and methods

In our institution, we have implanted 512 mechanical cardiac assist devices (InCor, 382, Berlin Heart, Berlin, Germany; Novacor N100, 99, World Heart Corp, Ottawa, Ontario, Canada; HeartMate VE23, ThermoCardio Systems Inc, Woburn, MA; DeBakey VAD, 8, Micromed Technology Inc, Houston, TX). Between November 1993 and September 2000, 94 patients with IDC were supported with a left ventricular assist device (LVAD) (Novacor N100, 84, World Heart Corp, Ottawa, Ontario, Canada; HeartMate VE, 10, ThermoCardio Systems Inc, Woburn, MA). During follow-up observation, while on the device, all patients demonstrated some improvement of heart function, the degree of which was documented during repeated pump-off studies by echocardiography. In 28 patients (24 supported by a Novacor, 3 by a TCI, and 1 by a Berlin Heart) Myocardial recovery was deemed sufficient to allow safe pump explantation. This decision was made strictly electively when heart function had reached normal values with regard to dimension and left ventricular ejection fraction in 24 patients. In 4 patients pump explantation was prompted by significant pump-related complications, such as pump pocket infection, pump valve infection, thromboembolism, or intractable pump pocket pain, when recovery seemed to be nearly complete.

Of this so-called "bridge-to-recovery" cohort, 4 patients had received the assist system in 1994, none in 1995, 7 in 1996, 7 in 1997, 1 in 1998, 2 in 1999, and 3 in 2000.

There were 26 men and 2 women, their ages at the time of pump implantation ranged from 18 years to 64 years (mean, 42 plus or minus 12 years). All patients suffered from IDC and their history of heart failure ranged from less than 1 year up to 17 years, (mean, 4 plus or minus 4 years). All patients were in end-stage heart failure, uncontrollable by intravenous inotropic medication, and all fulfilled the criteria required for a heart transplant candidate. However, these patients also showed at least a slight increase in liver enzymes and substances that were usually eliminated with urine. Implantation was done early enough in all patients to avoid dialysis.

At the time of device placement, hemodynamic data revealed elevated mean pulmonary artery pressures (35 plus or minus 6.5 mm Hg; range, 17 to 47 mm Hg) and a depressed cardiac index (1.8 plus or minus 0.31 min^-1 m^-2; range, 1.1 to 2.21 min^-1 m^-2). The left ventricular internal diameter in diastole (LVIDd) measured by echocardiographic motion mode ranged from 62 mm to 93 mm (mean, 75 plus or minus 8 mm). Left ventricular ejection fraction (LVEF), calculated from two reliable orthogonal views using biplanar Simpson’s rule, was quite uniform in all patients and ranged from 10% to 20% (mean, 16 plus or minus 3%).

Implantation was performed through median sternotomy with the creation of a large tissue pocket in the left upper quadrant of the abdominal wall with standard normothermic extracorporeal circulation. For implantation of the apical cannula, a short period of induced ventricular fibrillation during pulmonary artery venting was applied; otherwise, the implantation was performed on the beating heart.

Pump-off studies were conducted once a week after device placement. With a regularly running pump, if LVEF and LVIDd revealed normalization of cardiac function (LVEF 40% to 45%) and dimension (LVIDd less than 60 mm), the pump was set at the lowest possible pumping frequency. Eventually, the pump was stopped to evaluate the heart without mechanical support. To avoid thrombus formation inside the pump, 10,000 international units of heparin were administered before stopping the pump. Additionally, the device was allowed to pump once a minute.

After patients left the intensive care unit and were hemodynamically and physically stabilized, aggressive medical treatment for heart failure was initiated. This included beta-blockers, angiotensin-converting enzyme inhibitors, aldosterone-antagonists, digitalis, low-dose loop diuretics, electrolytes, trace elements, and a cocktail of antioxidants and enzymes. This medical regimen was aimed at attaining afterload reduction, a moderate heart rate, volume restriction, oxidative stress compensation, and increased fibrinolysis.

Once the degree of recovery is deemed complete, the pump is turned to a fixed-rate working mode to exert some moderated load on the ventricular muscle and, thus, "train" the heart for later pump explanation. This is one in incremental steps so that the minimal fixed rate mode of 60 bpm (i.e., maximum possible loading of the ventricle) will be reached within 2 weeks.

Pump explanation followed the fundamental rule of maintaining the recovered heart in a state that is as unmolested as possible. The apical cannula and the aortic graft are left in place; the pump body is simply removed by opening the tissue pocket; and the cardiac-side ends of the grafts are clamped, disconnected and oversewn.

Following explantation, patients were closely observed and treated with sodium warfarin for 6 months to avoid thrombus formation from the remnants of the inflow and outflow cannulae. As soon as possible after the operation, heart failure medication, such as beta-blockers, angiotensin-converting enzyme inhibitors, aldosterone-antagonists, digitalis, low-dose loop diuretics, electrolytes, trace elements, and a cocktail of antioxidants and enzymes that was given prior to device removal was restarted to maintain blood pressure and left ventricular afterload. Heart rate was controlled at the lowest rate possible (systolic blood pressure 100 mm Hg, resting heart rate 55 bpm). Transthoracic echocardiography was performed daily or every other day. Repeat echocardiography included determination of LVIDd and LVEF in all patients; more recently, peak systolic velocity (Sm) was added to the follow-up routine. Clinical follow-up was complete for all patients. No exercise testing or myocardial oxygen consumption tests were performed for the first 2 or 3 months postoperatively.

Myocardial morphology was studied in 24 apical core samples obtained at the time of pump implantation and, more recently, in 8 patients from left heart endocardial biopsy specimens.

Results

The time course of the recovery process during ventricular unloading was quite variable, since the best achieved heart function was reached between 1 month and 26 months (mean, 5 plus or minus 5 months). Optimal left heart values (LVEF more than 45 and LVIDd less than 55 mm) were obtained in 18 patients; in 10 patients less than optimal left ventricle (LV) data (LVEF 30% to 44%; mean, 39 plus or minus 4%; and LVIDd 56 to 64 mm; mean, 62 plus or minus 4 mm) were considered sufficient for pump explantation in view of an urgency. The urgency was caused by thromboembolism, pulmonary bleeding, infection of the pocket with a trend toward systemic infection, and chronic bleeding of inflow or outflow cannulas. Out of the 28 patients weaned from the device, 16 patients have persistently demonstrated normalized heart function with follow-up times of more than 5 years in 3, more than 3 years in 6, more than 2 years in 3, more than 1 year in 2 and less than one year in 2. These numbers result in a total follow-up of 42 years with a mean of 2.6 years.

Three patients died after 3, 8, and 120 days from septic shock, massive pulmonary bleeding, and pulmonary embolism, respectively. All were unrelated to cardiac disease.

One patient died 2.5 years after explantation from a catastrophic hemorrhage and a persistent apex infection, but with excellent heart function.

In 9 patients, signs of recurrent heart failure appeared within the first 2 months after explantation and progressed further (Group A). These patients were listed for transplantation after 1 to 17 months (mean, 6 plus or minus 4 months); 8 patients have since been transplanted, but one died while on the waiting list.

Thus, if well-preserved heart function for more than 6 months after pump explantation is declared a success (Group B), our experience shows that success was achieved in 60% of the patients weaned and in 18% of the IDC cases supported by a suitable LVAD. If we omit those patients who died from conditions unrelated to cardiac disease and omit the 2 who were nonelectively weaned with only moderate recovery (in whom the need of a heart transplant was anticipated), then the success rate in 70% with respect to all patients weaned. When patients with a persistently well-recovered heart function (Group B) were compared with those who suffered recurrent heart failure (Group A), the following differences became apparent (see Table 1).

The relevance of the speed of the initial recovery after assist implantation, as documented by LVEF and LVIDd, and the completeness of the recovery for anticipating persistent recovery is well illustrated in Figure 1.

View larger version (19K): [in this window] [in a new window]   Fig 1. Graphic presentations of the course of LVIDd (left) and LVEF (right) in Groups A and B. Left ventricular ejection function (LVEF) responds faster during recovery than changes in dimensions (LVIDd), and reaches normal values in successful cases. The last data on the curves represent those obtained most recently (Group B) or at time of listing for heart transplantation (Group A). (LVEF = left ventricular ejection fraction; LVIDd = left ventricular internal diameter in diastole.)

View larger version (155K): [in this window] [in a new window]   Fig 2. Histology of the myocardium obtained from the apical core excised at time of pump implantation. Fibrosis (dark structures) on histomorphometry amounts to 41 volume percent.

View larger version (154K): [in this window] [in a new window]   Fig 3. Histology of the myocardium obtained by a left heart endocardial catheter biopsy immediately before pump explantation in the same patient as in Figure 2 with a well-recovered heart. Fibrosis (dark structures) on histomorphometry amounts to 26 volume percent.

The most important revelation of our program of "bridge-to-recovery" in end-stage IDC has been the good long-term result, which now amounts to 5.5 years of persistent and complete normalization of heart function in our first patient, who underwent LVAD explantation in March 1995 after 5 months of unloading with a Novacor LVAD [1, 7]. This patient and two more of the first 6 treated in this manner experienced similarly favorable, long-term rehabilitation. One patient had to be transplanted due to recurrent heart failure, one died on the waiting list and another of the 6 original patients lived for 2.5 years with excellent heart function, but subsequently died from left apical hemorrhage (Fig 4). This latter patient had a bacterial infection of the myocardium around the apex prior to pump explantation. As this infection could not be treated successfully even after removal of the cannula, retrospectively the question remains whether explantation of the device rather than transplantation was the right decision for this patient.

View larger version (128K): [in this window] [in a new window]   Fig 4. The 6 patients who had pump explantation in the years 1995 and 1996. The patient in the back row, left, was the first to go through the "bridge-to-recovery" process, and it is now 5.5 years since he underwent explantation. He has a normal heart that is fully working. The same applies to the patients in the front row on the left and on the right. The 2 other patients in the back row had recurrent heart failure; 1 patient was transplanted and the other died on the waiting list 2 years after pump explantation. The patient in the front row, center, had excellent heart function for 2.5 years after pump removal, but died from a catastrophic hemorrhage in a chronically-infected left heart apex.

Persistent restoration of heart function, even in far advanced cases of IDC, may be obtained by prolonged unloading of the heart with LVAD and apical drainage. It appears that a certain proportion of IDC patients who are currently accepted as assist candidates, (ie, patients with end-stage heart failure unresponsive to inotropic support), may have the potential for complete cardiac recovery. Under the stringent acceptance conditions currently used, this proportion may amount to 15% to 20% of patients [8, 9]. This percentage may be quite different when the step is taken to electively implant LVADs in patients under stable circulatory conditions.

When addressing the question of how to characterize patients with such potential, several data suggest that hearts that are less chronically altered have a better prospect for recovery. Patients with long-term good results were younger in age, had a shorter history of heart failure, and showed faster and more complete restoration of function on the pump. In addition, the amount of fibrosis, albeit studied in only a few cases, seemed to diminish during the unloading period.

The change in fibrosis places patients with a good prospect for recovery somewhere between those with long-term chronically altered function and considerable fibrosis and those patients with acute inflammatory heart disease, such as acute viral myocarditis. In children with acute viral myocarditis, we have seen a dramatic and complete recovery in practically noncontracting hearts when supported by an assist device for only 2 or 3 weeks [10].

Worldwide research is focusing on a host of molecular biologic parameters related to inflammation or an abnormal response to receptors to identify patients who might benefit from mechanical unloading. So far none of the complex studies have fulfilled these expectations convincingly.

Similarly, morphologic studies of the myocardium so far have failed to arrive at reliable differences between those patients who respond to unloading and those who do not. However, we have observed that during the unloading period, fibrosis decreases most in patients who have good long-term recovery.

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]
2. Goldstein D.J., Oz M.C., Rose E.A. Implantable left ventricular assist devices. N Engl J Med 1998;339:1522-1533.[Free Full Text]
3. Hunt S., Frazier O.H. Mechanical cardiac support and cardiac transplantation. Circulation 1998;97:2079-2090.[Free Full Text]
4. DeBakey M.E. Left ventricular bypass pump for cardiac assistance B clinical experience. Am J Cardiol 1971;27:3-11.[Medline]
5. Nakatani T., Sasko Y., Kumon K., et al. Long-term circulatory support to promote recovery from profound heart failure. ASAIO J 1995;41:M526-M530.[Medline]
6. Marelli D., Laks H., Amsel B., et al. Temporary mechanical support with the BVS 5000 assist device during treatment of acute myocarditis. J Card Surg 1997;12:55-59.[Medline]
7. Hetzer R., Mueller J., Weng Y., et al. Cardiac recovery in dilated cardiomyopathy by unloading with a left ventricular assist device. Ann Thorac Surg 1999;68:742-749.[Abstract/Free Full Text]
8. Mancini D., Beniaminovitz A., Levin H., et al. Low incidence of myocardial recovery after ventricular assist device implantation in patients with chronic heart failure. Circulation 1998;98:2383-2389.[Abstract/Free Full Text]
9. Hummel M., Czerlinski S., Friedel N., et al. Interleukin-6 and interleukin-8 concentrations as predictors of outcome in ventricular assist device patients before heart transplantation. Crit Care Med 1994;22:448-454.[Medline]
10. Hetzer R., Loebe M., Potapov E.V., et al. Circulatory support with pneumatic paracorporeal ventricular assist devices in infants and children. Ann Thorac Surg 1998;66:1498-1506.[Abstract/Free Full Text]

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