Although being obtained in one single LVAD case, our data confirms previous observations in long term assisted patients: by an ejecting left ventricle the exercise CO exceeds the device output, contributing to yield an exercise capacity similar to moderately severe stable heart failure subjects (2,6,19). Additionally, because we performed an extensive hemodynamic and neuro-hormonal evaluation, we were able to observe after training further left ventricular unloading, and an increased right ventricular (the nonassisted chamber) load at peak exercise leading to a decrease in this chamber’s ejection fraction. After training, we observed a decreased neuro-hormonal drive for a given work rate, although the orthosympathetic stimulation may be higher at the enhanced maximal power. Moreover, the exercise blood lactate and ventilatory drive are lessened after training, whereas the oxygen pulse is increased for a given work rate.
Our data fit with the several previous studies on the postrehabilitation exercise capacity of LVAD supported patients (2,6,11,12,15,17,19). These studies have reported peak &OV0312;O2 in the range 14.1–17 mL·min-1·kg-1 (Table 4), all measured after the patient’s rehabilitation. Conversely, our report describes the improvements gained by exercise training in a previously moribund mechanically assisted patient. The peak work rate increased by 167% and the peak &OV0312;O2 increased by 56% during the 6 wk of training, but the peak exercise cardiac output remained unchanged (Table 3). This is consistent with the muscle hypothesis of exercise intolerance during heart failure (3,20). Indeed, the beneficial effects of exercise training resulted essentially from muscle metabolism and peripheral blood output redistribution changes, without improvements in central hemodynamic function in heart failure patients (13,22,32). We and others have shown in heart transplant, or heart failure patients, that retraining provokes an increase in the muscular mitochondrial density (5,16). Interestingly, after LVAD assistance and retraining, our patient reached the peak &OV0312;O2 that he had when in stable NYHA class III heart failure, at the time of initial evaluation for transplantation. In the recent report by Mancini et al. (19), the LVAD group had a significantly better peak &OV0312;O2 than the severe heart failure group, and the LVAD patients’ VT was equivalent to peak exercise in their heart failure patients. These improvements in gas exchange elicited by retraining are also prominent in Figure 1 where a slow &OV0312;O2 component exists even at 30W before training, whereas it occurs only at 60 W after training. As this slow component results from the type II muscle fiber recruitment (1), a lower percentage of such fibers are probably recruited for a given submaximal work rate after training. As previously stated the measured systemic CO was adequately related to &OV0312;O2(14) in our patient suggesting that there was no obvious deficit in central oxygen transport. Jaski et al. (12) were the first to observe in LVAD patients that the exercise CO exceeds the device output because the left ventricle starts to eject part of its stroke volume through the aortic valve, in parallel with the LVAD, an observation consistently found thereafter (2,11,19) ourselves included. Because the difference between the exercise systemic and device output is larger after training, the chronic left ventricular unloading, together with retraining, might have improved the left ventricular reserve (Table 2). This is also suggested by the benefits we observed on the filling pressures (Fig. 2). Therefore, both LVAD unloading and exercise training are likely to interact to yield a decreased left ventricular preload for any given level of exercise. Accordingly, the left ventricular pressure-volume relation, myocyte hypertrophy, and plasma volume are normalized by LVAD unloading (10,18,34), with beneficial effects on left ventricular morphometry and on histological signs of myocyte injury (26). Training might also participate in the decreased ventricular load because it diminishes the excess neuro-hormonal stimulation for any given submaximal work rate (3,4). This deserves further study. The effects of exercise and training on the right ventricle deserves also further attention: Jaski et al. (11) suggested that the exercise cardiac output is not limited by the unassisted right ventricle in the short-term assisted patient. Our patient’s right ventricular ejection fraction increased with exercise at time of initial assessment, but it decreased toward resting levels during heavy exercise after training, when the muscular improvements induced by retraining allow the exercise to reach a sufficiently high work rate.
The main limitation of this case study concerns the fact that we obtained data in one single patient. Therefore, our observations can only serve as guide for subsequent studies. Nevertheless, because our hemodynamic and gas exchange data are closely consistent with data previously reported after rehabilitation in LVAD patients (Table 4), we are convinced that it represent the average LVAD recipient. Another limitation concern the fact that our study does not permit us to separate the improvements due to retraining from those due to left ventricular unloading only. Because peak exercise CO remains similar before and after training, the beneficial muscular metabolic or vasomotor effects are likely to result from retraining, whereas the decrease in filling pressures and beneficial neuro-hormonal effects most likely result mainly from unloading with a contributing effect of retraining (10). Nevertheless, our preliminary data may help to design the necessary further studies on this topic. Because portable electrically actuated devices have become available (7), very prolonged LVAD support up to 794 d (30) have been reported, sometimes with sufficient heart recoveries to allow successful explantations of the LVAD without subsequent cardiac transplantation (30). This supposes that LVAD implantation can be seen as an independent therapeutic option for the dying heart failure patient, either as a permanent mechanical assist or as a bridge to recovery rather than as a bridge to transplantation (24,27,30). In this view, a comprehensive rehabilitation approach of the patient is mandatory, with its necessary exercise retraining program. Such an approach has been shown feasible even at a large scale (23), but the mechanisms that lead to improvements remained to be made precise. On the other hand, the assessment of the physiological response to exercise might reveal essential, especially in terms of right ventricular function and neuro-hormonal responses, to assess the long term safety of the LVAD assistance option without subsequent transplantation.
We conclude that exercise training in the previously moribund patient subject to left ventricular mechanical assistance results in beneficial metabolic muscular effects at submaximal exercise, without deleterious hemodynamic and neuro-hormonal consequences. Nevertheless the safety of exercise at near maximal level, as well as the long term consequences of regular training, remain to be examined.
We are indebted to Prof. Bernard Eisenmann, Prof. Jean-Georges Kretz, and Dr. Jean-Claude Thiranos for their support, the nurses team of our cardiovascular surgery department for their enthusiastic participation, and our patient who gave us lessons of hope.
This work has been supported in part by the INSERM network Activité Physique, Muscle et Handicap.
Address for correspondence: Bertrand Mettauer, M.D., Ph.D., Unité Fonctionnelles des Explorations Cardio-circulatoires à L’Exercice et Service de Chirurgie Cardio-Vasculaire, Pavillon Chirurgical A, Hôpitaux Universitaires de Strasbourg, 1, Place de L’Hôpital, 67091 Strasbourg Cedex, France; E-mail: Bertrand.Mettauer@physio-ulp. u-strasbg.fr.
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