Continuous-flow Left Ventricular Assist Devices: Clinical and Technical Aspects

In view of the shortage of donor hearts, continuous-flow Left Ventricular Assist Devices (cf-LVADs) have become an effective therapeutic option to bridge heart failure patients to heart transplantation. The subject of this thesis is the clinical and technical aspects of continuous-flow Left Ventricular Assist Device (cf-LVAD) therapy. The clinical results of the University Medical Center Utrecht using the Heartmate II LVAD (HM II) are presented. The analysis of 85 HM II patients demonstrated that 1 and 2 years actuarial survival of patients with this device was 81% and 76% and comes very close to that of patients after heart transplantation. In general, the HM II LVAD therapy was considered a successful life-saving therapy, albeit still associated with serious adverse events. As blood pressure measurements are difficult in patients with a cf-LVAD, the accuracy of a new blood pressure measurement monitor, the Nexfin, was evaluated. The monitor was first validated in a general population, then under conditions of reduced pulsatility with cardiopulmonary bypass, and eventually in patients with cf-LVADs. The Nexfin was able to assess blood pressure appropriately under during cf-LVAD support, while the blood pressure and echocardiography were complimentary in regards to cardiac and circulatory support in patients with a cf-LVAD. During exercise studies total cardiac output increased considerably while the cf-LVAD flow only increased moderately at maximum exercise. The Systemic Vascular Resistance also decreased considerably and showed the strongest correlation with Total Cardiac Output, while the exercise capacity were on average half of the predicted capacity for normal subjects when corrected for age and gender. Important affects of cf-LVAD support were aortic valve regurgitation (AR) and aortic valve commissural fusion. An analysis of 58 patients revealed that only 15% of the patients were free from AR throughout cf-LVAD support while AR appeared as diastolic or continuous AR, or also systolic AR in 10% of the patients with AR. Macroscopic examination of 15 explanted hearts revealed that 60% of the aortic valves had fusion of single or multiple commissures. Histological analysis showed that aortic valve commissural fusion was a non-inflammatory process, where commissures seemed to initially stick to each other, eventually resulting in prominent changes of the aortic valve morphology. Patients with continuous aortic valve closure (full support) did have statistically larger total fusion of the commissures compared to those on partial support. Also many of the patients with commissural fusion had developed AR while on cf-LVAD support. A mathematical computer simulation was used to evaluate changes in myofiber contractility and myocardial tissue stiffness of the left ventricle during cf-LVAD support. Simulations were done considering multiple pump speeds. The simulations showed that blood pressure derived parameters and aortic valve opening rather than echocardiography derived parameters responded in opposite direction to changes of myofiber contractility and myocardial tissue stiffness. The results and discussion of the studies may guide future evaluation strategies and technological development in the field of cf-LVAD therapy