Initial FDA Post-Approval Study INTERMACS Registry Results with a Continuous Flow Left Ventricular Assist Device as a Bridge to Heart Transplantation

Introduction: The HeartWare is a small centrifugal left ventricular assist device (LVAS). We report a health-related quality of life (QOL) and neurocognitive assess- ment from a multi-center prospective non-randomized study of the HeartWare LVAS. Methods: Fifty patients (age 49 6 13 {range 20-75} yrs) were enrolled at 5 centers in Europe and Australia. Results are reported for a sub-sample of patients with com- plete data. The neurocognitive battery consisted of measures of verbal memory, cog- nitive speed, planning ability, visual perception, and language. Data were analyzed using repeated measure ANOVA. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was used to measure self-reported health-related functional status and QOL in 9 domains. Results: Actuarial survival was 90% at 180 days and 86% at 1 year. As a group, health-related QOL improved for every subscale of the KCCQ, most notably in symptom burden, quality of life, physical limitations and overall functional status across the post-implantation testing periods compared to pre- implant. Individual analyses showed that 46% reported clinically significant improve- ment in QOL, 46% no change, and 8% worsening at week 4 post-surgery when compared to pre-surgery. Moreover, 64% of the sample reported improvements in QOL while 36% reported no change by week 26 compared to pre-surgery. All patients who were tested 1 year after surgery reported significant improvements in QOL. Prior to undergoing LVAD implantation, patients were moderately impaired as a group on tests of memory and mildly impaired on cognitive speed compared to age-matched normative data. Twenty-six weeks after surgery, memory perfor- mance remained similarly impaired compared to before surgery while cognitive speed significantly improved. Planning ability, visual perception, and language remained the same or similar at week 26 compared to before surgery. One year after surgery, cognitive test performance remained similar to week 26. Conclusions: Qual- ity of life is significantly improved at 4-, 26- and 52-weeks post-LVAS implantation. Some improvements were noted in neurocognitive functions at 26 weeks (i.e. cogni- tive speed) and results at 52 weeks were similar to those at 26 weeks. Introduction: There are several animal models using coronary occlusion that try to mimic ischemic heart failure (IHF). These techniques create infarctions by mechanical disruption of blood flow but lack the biomass of thrombus that occurs during plaque rup- ture that we see clinically. We propose a novel pre-clinical large animal model of car- diac failure developed by direct injections of autologous platelet aggregates (APAs) into the coronary circulation which results in IHF. Methods: Platelets were isolated from the whole ovine blood before embolization procedure (EP) and aggregated using thrombin. Each animal (n56) was anesthetized and catheter was placed into coronary circulation via left carotid artery access. APAs were injected into the circumflex coro- nary artery under fluoroscopic guidance. Cardiac injury was monitored by troponin levels collected after each EP for 3 days. IHF was evaluated by echo-based assessment of ejection fraction (EF), left ventricular end-systolic dimension (LVESd), left ventric- ular end-systolic volume (ESV), left ventricular end-diastolic dimension (LVEDd), and left ventricular end-diastolic volume (EDV). Results: Each animal developed IHF within 4-12 weeks from first EP. Cardiac injury was monitored with troponin levels (ng/ml) rising from 0.01 6 0.00 to 216, 66 and 24 (mean value) at days 1, 2 and 3 post EP, respectively. EF dropped from 67 6 0.9% to 26 6 0.01% (mean value). LVESd increased from 2.7 6 0.06cm to 5.0 6 0.3cm. ESV increased from 27 6 1.5ml to 116 6 15ml, LVEDd increased from 4.3 6 0.1cm to 5.6 6 0.3cm, and EDV increased from