[Show abstract][Hide abstract] ABSTRACT: -The long-term durability and prognostic significance of improvement in renal function following mechanical circulatory support (MCS) has yet to be characterized in a large multicenter population. The primary goals of this analysis were to describe serial post-MCS changes in estimated glomerular filtration rate (eGFR) and determine their association with all-cause mortality.
-Adult patients enrolled in INTERMACS with serial creatinine levels available (n=3,363) were studied. Early post-MCS, eGFR improved substantially (median improvement 48.9%, p<0.001) with 22.3% of the population improving their eGFR by ≥100% within the first few weeks. However, in the majority of patients this improvement was transient, and by one year, eGFR was only 6.7% above the pre-MCS value (p<0.001). This pattern of early improvement followed by deterioration in eGFR was observed with both pulsatile and continuous-flow devices. Interestingly, poor survival was associated with both marked improvement (adjusted HR=1.64, 1.19-2.26, p=0.002) and worsening in eGFR (adjusted HR=1.63, 1.15-2.13, p=0.004).
-Post-MCS, early improvement in renal function is common but appears to be largely transient and not necessarily indicative of an improved prognosis. This pattern was observed with both pulsatile and continuous-flow devices. Additional research is necessary to better understand the mechanistic basis for these complex post-MCS changes in renal function and their associated survival disadvantage. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00119834.
[Show abstract][Hide abstract] ABSTRACT: Rationale: The Calcium Up-Regulation by Percutaneous Administration of Gene Therapy In Cardiac Disease (CUPID 1) study was a phase 1/phase 2 first-in-human clinical gene therapy trial using an AAV1 vector carrying the cardiac sarcoplasmic reticulum ATPase pump (AAV1/SERCA2a) in patients with advanced heart failure. The study explored potential benefits of therapy at 12 months, and results were previously reported. Objective: To report long-term (3-year) clinical effects and transgene expression for the patients in CUPID 1. Methods and Results: A total of 39 patients with advanced heart failure who were on stable, optimal heart failure therapy, were randomized to receive intracoronary infusion of AAV1/SERCA2a in 1 of 3 doses (low dose-6 x 10(11) DNase Resistant Particles [DRP], middle dose-3 x 10(12) DRP and high dose-1 x 10(13) DRP) versus placebo. The following recurrent cardiovascular and terminal events were tracked over 3 years in all groups: myocardial infarction, worsening heart failure, heart failure-related hospitalization, ventricular assist device placement, cardiac transplantation and death. The number of cardiovascular events, including death, was highest in the placebo group, high but delayed in the low and mid dose groups and lowest in the high dose group. Evidence of long-term transgene presence was also observed in high dose patients. The risk of pre-specified recurrent cardiovascular events was reduced by 82% in the high dose versus placebo group, p=0.048. No safety concerns were noted during the 3-year follow-up. Conclusions: Following a single intracoronary infusion of AAV1/SERCA2a in patients with advanced heart failure positive signals in terms of cardiovascular events persist for years.
Circulation Research 09/2013; · 11.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: There are an increasing number of elderly patients with end-stage heart failure. Destination mechanical circulatory support is often the only therapy available for these patients who are not transplant candidates. The outcomes after continuous flow left ventricular assist device (CF LVAD) implant in older patients remains unclear. We undertook this multi-institutional study to quantify short-term and midterm outcomes after CF LVAD implant in the elderly. METHODS: We retrospectively analyzed all patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) national registry that underwent implant of a CF LVAD (June 2006 to April 2012). Patients were divided into 2 cohorts based upon age (<70 years [n = 4,439] and ≥70 years (n = 590]). Preoperative, intraoperative, and postoperative variables were analyzed. The primary endpoint, survival, was compared between cohorts. RESULTS: Patients age 70 and older were more hemodynamically stable pre-VAD implant as evidenced by INTERMACS profile and inotrope dependence. Perioperative outcomes, including median bypass time (89 vs 89 minutes) and length of stay (0.657 vs 0.657 months) were similar between cohorts (p = not significant). Kaplan-Meier analysis revealed a significant difference in 2-year survival between patients aged 70 years or greater (63%) and less than 70 (71%, p < 0.001). Multivariable Cox proportional hazard analysis revealed age as an independent predictor of mortality during follow-up (p < 0.001). Nonetheless, midterm cumulative survival in the older cohort was still reasonable (63% at 2 years). CONCLUSIONS: Multi-institutional analysis revealed advanced age as a predictor of increased mortality after CF LVAD implantation. Careful patient selection is critical in the elderly to optimize long-term outcomes after CF LVAD implantation.
The Annals of thoracic surgery 05/2013; · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
This study investigated how the initial intended strategy at left ventricular assist device (LVAD) implantation influenced patient outcomes.
Left ventricular assist device implantation strategy impacts candidate selection, reimbursement, and clinical trial design; however, concepts of device strategy are continuing to evolve.
For patients entered in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) receiving a primary continuous flow LVAD between March 2006 and March 2011, initial strategies were bridge to transplant (BTT), bridge to candidacy (BTC) for transplant, and destination therapy (DT). Primary analyses compared BTT, BTC, and DT outcomes at 6, 12, and 24 months.
Among 2,816 primary LVAD recipients, implant strategy was 1,060 (38%) BTT, 1,162 (42%) BTC (likely to be listed 796, moderately likely 282, unlikely 84), and 553 (20%) DT. Compared with BTC/DT, those listed at implant (BTT) had similar degrees of ventricular dysfunction and hemodynamic derangement but generally less comorbidity. Survival (alive with LVAD or transplanted) was superior at 24 months for BTT versus BTC versus DT (77.7% vs.70.1% vs. 60.7%, respectively, p < 0.0001). Strategic intent changed over time, at 2 years 43.5% of BTT patients were no longer listed for transplant, but 29.3% of BTC patients were listed for transplant.
The currently accepted indications only account for 58% of LVAD implants. Across indications, patients differ by the number and types of comorbidities rather than the need for hemodynamic support. Regardless of initial implant strategy, patients often have long durations of support, and strategies often change over time, challenging the regulatory categorization of LVAD recipients as either BTT or DT.