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Background Because of ongoing shortages of donors for heart transplantation, the use of donor candidates whose availabilities are the result of drug overdoses (ODs) has become increasingly prevalent, even though these donors carry a high preponderance of the now curable hepatitis C virus (HCV). This study investigated temporal trends and regional variabilities in HVC-positive (HCV+) allograft use in heart transplantation and assessed the relationship between the use of HCV+ graft donors and the use of OD donors as well as assessing waitlist and post-transplant outcomes. Methods and Results A retrospective review of the United Network for Organ Sharing database assessed adults listed for heart transplantation. Patients were stratified both temporally into pre-HCV and HCV eras related to HCV+ graft use trends and regionally by degree of HCV+ allograft use. Regions of high HCV+ donor use were associated with an increase in OD donor access by 7.8% across eras compared to 0.4% in low HCV+ donor-use regions. One-year waitlist mortality decreased from 4.7% to 2.5% across eras in high HCV+ donor-use regions (P= 0.001) and remained roughly the same as before in low HCV+ donor-use regions (3.0% vs 2.4%; P= 0.244.). Post-transplant survival at 1 year remained similar across eras. Conclusions HCV+ donor allograft use can help to optimize donor use, decreasing waitlist mortality without compromising early survival. Ongoing assessment is essential to ensure long-term safety and efficacy of using HCV+ donors.

Background Impella (Abiomed Inc, Danvers, MA) is a temporary mechanical support device positioned across the aortic valve, and can be used to support patient before LVAD implantation. There are no data on the incidence of aortic insufficiency (AI) in patients supported with Impella as a bridge to durable LVAD implantation. We sought to assess the incidence of AI in patients with Impella support as a bridge to durable left ventricular assist device (LVAD) implantation. Methods We reviewed all patients undergoing primary LVAD implantation at the University of Pennsylvania from January 2015 onward, comparing those supported with Impella as temporary mechanical support with those supported by either venoarterial extracorporeal life support or an intra-aortic balloon pump. We reviewed transthoracic echocardiography preoperatively, as well as at 1 week, 1, 3, 6, 9, and 12 months after LVAD implantation. Results A total of 215 echocardiograms were analyzed in 41 patients. Eleven patients were supported with Impella before LVAD implant—6 patients with Impella alone (5 with Impella CP, 1 with Impella 5.0) and 5 with Impella in conjunction with venoarterial extracorporeal life support (2 with Impella 2.5, 2 with Impella CP, and 1 with Impella 5.0). After LVAD implant, mild or moderate AI developed in 82% of patients supported with Impella (9 of 11) compared with 43% of those without Impella (13 of 30) (P = .038). Conclusions Patients supported by Impella as a bridge to durable LVAD have a higher risk of developing AI. Further studies are needed to assess this risk as the use of the Impella increases.

Background Heart transplant volume varies significantly among centers. We hypothesized that centers where the transplant team routinely accepts organs previously declined by other centers and where operating room availability is unrestricted have higher transplant volumes. Methods and Results We used the potential transplant recipient sequence number in the United Network for Organ Sharing database as a surrogate for graft acceptance threshold and the number of transplantations occurring on weekends and 8 major holidays as a marker of center resource availability. Centers were classified as low-, medium-, or high-volume if the average annual number of transplants were, respectively, 30 over a 10-year period. From July 12, 2006, to December 31, 2015, 19,054 transplants were performed by 142 centers. There were 59 low-volume centers, 69 medium-volume centers, and 14 high-volume centers with median potential transplant recipient sequence numbers for transplanted candidates of 7 (interquartile range 3–11), 7 (5–10), and 15 (7–40), respectively (P = .002). The median proportion of off-hours transplantations performed by medium-volume centers was 28% (25%–31%) compared with 32% (29%–33%) by high-volume centers (P = .009). Five-year survival was equivalent among all centers (P = .053). Conclusions Transplants for candidates with high sequence numbers and unrestricted operating room availability are associated with increased center volume without sacrificing post-transplantation survival.

This study evaluates the Area Deprivation Index (ADI) as a novel prognostic metric of socioeconomic status for patients with a left ventricular assist device.A retrospective analysis of patients with a left ventricular assist device at a high-volume institution from 2007 to 2018 was conducted. Socioeconomic status was determined using the ADI, a multifactorial neighborhood-based metric where higher ADI denotes worse socioeconomic status. Patients were stratified into 4 ADI cohorts. Long-term survival was compared with multivariate analysis. Of the 380 patients stratified by ADI, 35 were in the 10th percentile or lower, 218 were in the 11th-50th percentile, 104 were in the 51st-89th percentile, and 23 were in the 90th percentile or higher. Baseline characteristics were comparable. On multivariate analysis, being male (hazard ratio [HR], 0.14; P = .01), bridge-to-transplant (HR, 0.14; P = .03), and not requiring biventricular support (HR, 0.02; P.01) were protective, whereas chronic kidney disease (HR, 9.07; P.01) and an elevated total bilirubin (HR, 3.56; P = .02) were harmful. The ADI as a continuous variable did not affect survival; however, categorically, a higher ADI was protective (ADI 90-100: HR, 0.07; P = .04).Socioeconomically disadvantaged patients had noninferior outcomes given appropriate pre-implant optimization and workup.

Background Pulmonary arterial compliance (PAC), a marker of right ventricular (RV) afterload, represented as the ratio of stroke volume (SV) to pulmonary artery pulse pressure (PP), has been shown to be prognostic in heart failure populations. Prior work has shown that the ratio of right ventricular outflow tract pulsed-wave Doppler velocity time integral (RVOT-VTI; an echo-derived estimate of RV SV) and PA systolic pressure (PASP), correlates well with PAC obtained from invasive hemodynamics in patients with heart failure with preserved ejection fraction (HFpEF). We sought to explore this relationship in patients with heart failure with reduced ejection fraction (HFrEF) in a pre-left ventricular assist device (LVAD) cohort. Methods From a cohort of 196 patients with HFrEF awaiting LVAD implant at the Hospital of the University of Pennsylvania from 1/2008 to 2/2015, 72 patients underwent quantitative analysis of pre-implant echocardiogram by an independent reviewer (median days between echo and invasive hemodynamics were 3 [IQR 1-7]). We examined the relationship between RVOT-VTI/PASP with invasive PAC (calculated as SV/PP) using Pearson's rank coefficient and multivariate linear regression analysis. Results There were 42 patients (58%) with sufficient study quality to generate RVOT-VTI/PASP. The median RVOT-VTI/PASP was 0.16 cm/mmHg (IQR 0.11-0.23) and the median PAC was 1.61 ml/ mmHg (IQR 1.36-2.37). There was a modest but significant correlation between RVOT-VTI/PASP and PAC (r2 = 0.47; p=0.002) (Figure). In multivariate linear regression modeling, the relationship between RVOT-VTI/PASP and PAC was maintained (beta-coef 5.5, p=0.015) after adjusting for PCWP (beta-coef -0.016, p=0.5) and PVR (beta-coef -0.24, p=0.03). Conclusions In this small HFrEF cohort, RVOT-VTI/PASP, a proposed non-invasive metric of RV afterload that can be readily obtained on routine echocardiography, correlates with invasive PAC. Additional larger studies among patients with HFrEF are needed to determine if this relationship is maintained and is robust enough for the non-invasive estimation of PAC.

Introduction Aortic incompetence (AI) is very common complication after continuous flow left ventricular assist device (LVAD) implantation, and can result in increased symptoms for LVAD patients. Recent advances in Transcatheter Aortic Valve Replacement (TAVR) technology has resulted in this becoming a potential therapeutic avenue for LVAD patients with AI. We report a case of TAVR implantation in a patient supported with a LVAD complicated by thrombosis. Case Report A 61-year-old female presented with STEMI. She was treated with primary PCI, but had progressive cardiogenic shock and was placed on VA-ECMO. Due to high PRA, she was unable to be listed for primary transplantation and underwent implantation of a Heartware LVAD (Medtronic) as bridge to decision. Her post-operative course was complicated by recurrent GI bleeding. Over the following 12 months, she was noted to have worsening AI on routine echocardiography, with worsening symptoms that persisted despite hemodynamic and echocardiographic-guided LVAD optimization. After heart team review, her anatomy was deemed appropriate for TAVR and she underwent implant of a 26mm Evolut Pro (Medtronic). The procedure was complicated by post-implant complete heart block on POD #4 requiring pacemaker implantation. She was discharged from the hospital, however over the next 3 months had recurrent episodes of low flow alarms that continued despite LVAD speed and medication optimization. A transthoracic echocardiogram did not reveal any abnormalities, although it was unable to visualize the TAVR leaflets. A multiphase 4D CT Angiogram was performed to rule out LVAD outflow graft obstruction, which revealed extensive hypoattenuating leaflet thickening involving all 3 leaflets of the TAVR with absent leaflet motion consistent with thrombosis of the prosthetic valve leaflets (See Figure). She was started on intravenous anticoagulation (unfractionated heparin), but this had to be ceased due to hemodynamically significant GI bleeding requiring multiple transfusions. LVAD speed was also attempted to be increased to minimize risk of aortic valve opening, but this was unable to be continued due to recurrent low flow LVAD alarms. Repeat imaging 3 months later showed continual thrombosis, and she has remained stable while awaiting transplantation. Summary We describe a novel complication of TAVR in LVAD patients. This case highlights the major diagnostic and management dilemmas that should be considered as this management strategy becomes more widespread in this patient population.

Introduction Chronotropic incompetence is very common after heart transplant. The extent to which it affects the functional capacity of heart transplant patients is unknown. We hypothesize that a higher heart rate responsiveness would be associated with improved peak oxygen uptake and may have long-term prognostic impact. Methods We performed a retrospective analysis of all patients who underwent heart transplantation and cardiopulmonary exercise testing (CPET) in the first post-transplant year at a single large academic center between the year 2000 and 2011. Peak VO2 and total exercise time were assessed by CPET. Heart rate responsiveness was defined as the difference between peak and resting heart rate during CPET. The association of heart rate responsiveness with peak VO2 and total exercise time was analyzed using multivariable linear regression, and survival analysis was performed via a cox proportional hazard model. Results CPET was performed at our institution in 271 patients during the first year post heart transplantation at a median of 2.3 months. Subjects were 82% male, age 55 (IQR 45-61) at time of CPET. After multivariate adjustment, each ten beat/min increase in heart rate responsiveness was associated with a 0.9 ml/kg/min increase in peak oxygen consumption (p Conclusions Chronotropic incompetence after heart transplant is associated with decreased functional capacity but is not a prognostic indicator of mortality after transplant.

Introduction The development of aortic incompetence (AI) after left ventricular assist device (LVAD) implantation occurs in 25-30% of all LVAD patients and contributes to increased morbidity. While the underlying pathophysiology is still unclear, previous pathology studies have shown that LVAD patients have accelerated aortic valve cusp remodeling when compared to other heart failure patients; this has been postulated to be the mechanism for AI in the LVAD population. A number of studies have attempted to identify populations that are at risk of developing AI, but none have assessed the effect of preoperative aortic valve sclerosis as a risk factor. We sought to assess the impact of preoperative aortic valve sclerosis on the development of AI in patients requiring LVAD support. Methods We retrospectively reviewed medical charts of patients implanted with Heartmate II (Abbott) and Heartware HVAD (Medtronic) LVADs at a large academic medical center between January 2011 and September 2018. We reviewed transthoracic echocardiography preoperatively and at 1, 3, 6, 9, and 12-months post LVAD implantation. Preoperative aortic valve thickening was predefined as mild or worse sclerosis on transthoracic echocardiogram. Patients with more than mild AI preoperatively or concomitant aortic valve replacement (AVR) were excluded from the analysis. Results A total of 660 echocardiography studies in 176 patients on LVAD support (mean age 55.1±14.0 years old, 84% male, 36.9% HVAD, 63.1% Heartmate2) were identified and analyzed. 25.5% were identified as bridge to transplant, 55.7% as destination therapy, 15.3% as bridge to decision and 3.4% as bridge to recovery. 21.6% were INTERMACS profile 1 and 71.0% were INTERMACS 2 and 3. 49.4% of the patients (n=87) had at least mild AI over the follow up period. The main risk factors identified for the development of AI post-operatively were aortic valve thickening on preoperative echocardiography (61.9% vs 42.4%, p = 0.014) and older age (58.9 ± 13.1 vs 51.4 ± 13.1, p = 0.003). On a multivariate analysis, patients with preoperative aortic valve thickening had a 2.1 times increased risk of developing mild or worse AI post LVAD implant (odds ratio of 2.1, p = 0.027). Conclusions Occurrence of aortic insufficiency is very frequent in patients on prolonged LVAD support. Our study is the first to show that preoperative aortic valve thickening is a significant risk factor for postoperative AI and should be included as a risk factor in decision making prior to LVAD implantation.

Background Early graft dysfunction after orthotopic heart transplantation is associated with worse survival and functional outcomes. However, the prognostic implication of acute cellular rejection (ACR) early after transplant is less well defined. Here, we analyzed the association between early ACR and post-transplant exercise capacity. Methods We performed a retrospective analysis of all heart transplant patients who underwent cardiopulmonary exercise testing (CPET) within a year of transplant at a single large academic center between 2000 and 2011. Early ACR was defined as cellular grade 2R or 3R histopathology seen on biopsy within 3 months of transplant. Exercise capacity was assessed during CPET by 1) peak VO2 and 2) total exercise time. CPET performed prior to diagnosis of rejection were excluded. The association between early ACR or grade of ACR and exercise parameters was analyzed using linear regression. Results A total of 230 patients (median age 55 [IQR 45-61], 79.6% male) who received a heart transplantation at our institution between 2000 and 2011 underwent CPET during the 1st year. Of these, 12% (n=40) developed early grade 2R rejection and 5% (n=12) developed early grade 3R rejection. No antibody mediated rejection (including hyperacute) was seen in this timeframe among patients who later underwent CPET. Neither peak VO2 (p=0.95) nor total exercise time (p=0.54) were predicted by early ACR of any grade. Conclusions Early cellular rejection does not predict worse exercise capacity in the first year after heart transplant. This inference is limited to patients who are able to undergo CPET.

The "high-risk donor" (HRD) label was applied to donors who met the Centers for Disease Control and Prevention criteria for high-risk behavior in 2004. The number of potential recipients who die awaiting orthotopic heart transplantation (OHT) has increased. Despite organ shortages, HRD grafts are often declined given infectious concerns. We hypothesized that recipients would have equivalent outcomes.We retrospectively analyzed the United Network of Organ Sharing adult heart transplant data from June 2004 to December 2013. OHT recipients were divided into 2 cohorts by donor status.During the study period, 37,408 OHTs were performed and 3196 (8.5%) patients received HRD grafts. Recipients of HRD were significantly older (P .0001) and had a higher body mass index (P .0001) compared with standard-risk donor recipients. No significant difference in waitlist time (P = .69) or blood type (P = .07) was noted. A higher number of HRD recipients were on mechanical circulatory support (35.6%) compared with standard-risk donor (33.3%, P = .009). Both grafts manifested similar, low rates of rejection before discharge (P = .88). One1 (84.3 vs 83%) and 5-year (71.2 vs 65.5%) survival was similar in the cohorts (log-rank P = .7571).HRD status does not significantly affect recipient outcomes after OHT. Increased use of HRD grafts could augment donor pool and decrease the mortality associated with long waitlist times.

Introduction: Ischemic cardiomyopathy is a global health concern. Endothelial progenitor cell (EPC) upregulation with granulocyte-monocyte colony stimulating factor (GMCSF) followed by stromal-cell derived factor-1a (SDF) directed EPC chemokinesis is a means of myocardial revascularization.We recently reported upregulated EPCs, enhanced neovasculogenesis and increased myocardial perfusion with this therapy. To further investigate the biologic mechanisms we studied hypoxia attenuation, myocardial preservation, and function. Hypothesis: Neovasculogenic therapy with SDF/GMCSF enhances myocardial function by attenuating hypoxia and preserving myocardium. Methods: Lewis rats underwent LAD coronary ligation and progressed into heart failure. At 3wks the animals were randomized to intramyocardial SDF and subcutaneous GMCSF injections as therapy or saline as control. 6wks post-ligation borderzone vascular endothelial growth factor (VEGF) levels were quantified by western blot analysis. Endogenous VEGF is produced in response to tissue ischemia, thereby serving as a marker for hypoxia. Myocardial viability was determined by apoptosis as measured by caspase-3 activity levels and preservation of myocardial mass. Myocardial function was measured by echocardiography. Results: This therapy attenuated hypoxia as evidenced by decreased VEGF production. Enhanced myocardial preservation was noted by diminished apoptosis and enhanced myocardial to body mass ratio. There was a significant improvement in myocardial function with SDF/GMCSF therapy. Conclusions: GMCSF EPC upregulation and SDF mediated EPC chemokinesis enhances myocardial function by reversing myocardial ischemia and enhancing myocardial viability.