Final Report Summary - VAD AND EXERCISE (VAD-Patient interaction: from rest to exercise) Heart failure is one of the main causes of death in industrialized countries. The disease can be slowed down or stopped with the use of medical therapy, but in a percentage of patients it progresses to end-stage heart failure. In this condition, patients require a heart transplantation, but due to the lack of donors this option is not always possible. An alternative is the use of a ventricular assist device (VAD) consisting of a hydraulic pump placed inside the chest. The VAD drains blood from the left ventricle and pumps it into the aorta, thus bypassing the native left heart in propelling blood to the systemic circulation. Thanks to the current technical improvements, a VAD is nowadays considered a valuable therapy, not only as a bridge to transplantation, but also as a destination therapy. The current clinical and research interest is focused on continuous-flow VADs, due to their small size, low invasiveness and mechanical durability. This new class of continuous-flow VADs is able to provide an amount of flow according to the pressure drop across the pump itself and to the pump speed set by the clinician. Therefore, unlike pulsatile devices, continuous-flow VADs have no capability of changing their output according to the patients’ venous return.According to this, there is an increasing clinical necessity for understanding how to estimate and modulate the optimal level of support (that is, the VAD rotational speed) to be provided to a patient according to the venous return and the residual functionality of the left ventricle. This is crucial during exercise, when the human body needs to increase its cardiac output to better oxygenate the peripheral tissues. VAD and Exercise is a project focused on investigating exercise capacity in VAD patients. In particular, the project is aimed at assessing the evolutions of the patients’ exercise capacity over time, and at investigating the effects of VAD speed changes on the patients’ performance. The main hypothesis of this project is that an increase in VAD speed during exercise might accommodate a higher cardiac output and therefore improve exercise capacity.To this end, we ran a clinical study in the University Hospitals of KU Leuven, enrolling patients that received a continuous-flow VAD. Each patient performed two maximal cardiopulmonary exercise tests (CPET) on the same day, one at constant VAD speed (Exp1), and the other with a manually increased VAD speed (Exp2). The main RESULTS of the study are listed below:1. The exercise capacity of VAD patients is on average only ~50% of that expected in a healthy condition. VADs have proven to successfully restore a stable hemodynamic condition in end-stage heart failure patients, but more clinical and research efforts should be directed towards evaluating secondary morbidity and quality of life. 2. The exercise capacity of VAD patients does not improve over time. We observed an improvement only in the first months after VAD implantation, but then patients reach a plateau and no further changes were observed in terms of exercise performance. 3. During a regular CPET test (Exp1), VAD flow naturally raises with the increase in workload. The VAD information, observed from the device monitor, revealed that VAD flow tends to increase during exercise even if the rotational speed is kept constant. The magnitude of this increase depends on the patients’ condition and it tends to be higher in weaker patients. 4. A VAD speed increase does not significantly improve exercise capacity. The comparison between Exp1 and Exp2 revealed no differences in terms of ventilation, hemodynamic and cardiac parameters.5. A VAD speed increase provides a benefit in terms of fatigue perception only in a small percentage of patients. We asked patients to score the fatigue perceived at the end of both Exp1 and Exp2 and to compare the two tests in case any difference was felt. Most of the patients claimed that no differences were observed, and that the level of fatigue was the same in Exp1 and Exp2. From the results we obtained, we can conclude that exercise physiology in VAD patients is a very complex matter that involves a high number of variables rather than just the VAD speed. Indeed, the VAD speed is only one small element in a much wider picture including many other parameters like heart, lungs, muscular function, blood anemia etc. From this project, we can conclude that more efforts should be made to improve exercise capacity, focusing not only on the VAD itself, but also on the patient’s (de)conditioned status, and on its residual cardiac function.Besides, due to the complexity of exercise physiology, involving both cardiovascular and respiratory variables, a computational cardio–respiratory simulator was developed in this project. It was specifically adapted to reproduce exercise physiology in heart failure, and especially beat-to-beat hemodynamic and respiratory responses to graded exercise (in a similar manner to a CPET test). The simulator offers a reliable representation of heart rate, blood flows, pressures, O2 and CO2 saturations and vascular resistances at rest and during exercise. As a last step, we also included the VAD support, simulated on the basis of a pressure-flow characteristic of some devices currently available in the market. The simulator allows to reproduce the interaction between the left ventricle and the VAD from rest to exercise, and to evaluate the effect of different VAD speeds on it. A schematic representation of the simulator is provided in Figure 1. The results of the present project will have an important IMPACT on the current treatment of VAD patients:1. MEDICAL AND SOCIAL IMPACT: the clinical study we conducted provides some indications about which parameters should be taken (or not) into account to improve patients’ exercise capacity. This will have some positive effects in the future on the patients’ quality of life and daily activity. Our next step will be to try to improve the exercise capacity of both VAD patients in destination therapy (since they will be more active and independent) and VAD patients waiting for a heart transplantation (since they will reach a fitter condition at the moment of the surgery). It is a social challenge to assure these patients not only a “stable hemodynamic” condition, but also a life style as close as possible to that of a healthy subject, so that they can return to work and maximize their social, psychological and physical functions. 2. EDUCATIONAL AND DISSEMINATION IMPACT: the cardio-respiratory simulator is a user friendly tool exploitable for VAD therapy optimization and patients’ clinical management improvement. Moreover, it can be used as an educational tool to train clinicians, technicians, and nurses on the use of a VAD and its effects on patients’ hemodynamics. VAD therapy is still a niche, and more efforts should be carried out to divulge it to the medical community so that more patients can benefit from it.3. TECHNOLOGICAL IMPACT: the project has an important potential impact also on VAD manufacturing. The simulator itself and the clinical study carried out in this project, provided some important indications about pros and cons of different VAD types. Moreover, the simulator can be used as computational test bench, where different VAD prototypes and speed modulation strategies can be tested.Contact details: Libera Fresiello, Department of Clinical Cardiac Surgery - KU Leuven. email: libera.fresiello@gmail.com final1-figure1.png
