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Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant. Immediately after transplant, %ddcfDNA was higher for Black patients (mean [SE]: 8.3% [1.3%] vs 3.2% [1.2%], p = 0.001). In the first week post-transplant, the rate of decay in %ddcfDNA was similar (0.7% [0.68] vs 0.7% [0.11], p = 0.78), and values declined in both groups to a comparable plateau at 7 days post-transplant (0.46% [0.03] vs 0.45% [0.04], p = 0.78). The proportion of Black patients experiencing AMR was higher than non-Black patients (21% vs 9% [hazard ratio of 2.61 [95% confidence interval: 0.651-10.43], p = 0.18). Black patients were more likely to receive a race mismatched organ than non-Black patients (69% vs 35%, p = 0.01), which may explain the higher levels of early allograft injury.

Infiltrative cardiomyopathies are an increasingly recognized cause of heart failure warranting systematic evaluation. Given overlap of clinical and imaging findings among etiologies of infiltrative cardiomyopathies, comprehensive evaluation, including a history and physical examination, advanced cardiac imaging, and sometimes endomyocardial biopsy, is required for diagnosis. We report a case of infiltrative cardiomyopathy in which endomyocardial biopsy confirmed diagnosis of cobalt-induced cardiomyopathy. The novel teaching points highlighted by this case report include identification of heavy-metal toxicity as a cause of infiltrative cardiomyopathy, and the outline of a diagnostic approach and management for cobalt-induced cardiomyopathy.

BACKGROUND Due to anatomic and physiologic concerns, prior generations of the left ventricular assist devices (LVAD) have frequently been denied to patients with small body size. However, outcomes in patients with small body surface area (BSA) following HeartMate 3 (HM3) LVAD implantation remain relatively unknown. METHODS A cohort of 220 patients implanted at a single center was divided into two groups: BSA ≤1.8 m2 (small BSA, n = 37) and BSA >1.8 m2 (large BSA, n = 183). We investigated baseline characteristics and clinical outcomes including survival and incidence of adverse events. RESULTS Small BSA patients were older (60 vs. 57 years), more likely female (60% vs. 20%), had a lower body mass index (24 vs. 32 kg/m2 ), lower incidence of diabetes (32% vs. 51%), history of stroke (5% vs. 19%), and left ventricular thrombus (0% vs. 11%). They had smaller left ventricular end diastolic diameter (64.8 vs. 69.3 mm). Pump speed and pump flows at discharge were lower in the small BSA group. Survival at 1 year and 2 years was 86% versus 87% and 86% versus 79% for small versus large BSA groups (p = 0.408), respectively. The rates of adverse events were similar between groups and there were no cases of confirmed pump thrombosis. The incidence of readmissions for low flow alarms was higher in the small BSA group (0.55 vs. 0.24 EPPY). CONCLUSIONS These findings demonstrate comparable outcomes in patients with small body size and suggest that this parameter should not be an exclusion criterion on patients who are otherwise candidates for HM3 LVAD implantation.

Background Many patients with American College of Cardiology/American Heart Association Stage D (advanced) heart failure are discharged home on chronic intravenous inotropic support (CIIS) as bridge to surgical therapy or as palliative therapy. This study analyzed the clinical trajectory of patients with advanced heart failure who were on home CIIS. Methods We conducted a single-institution, retrospective cohort study of patients on CIIS between 2010 and 2016 (n = 373), stratified by indication for initiation of inotropic support. Study outcomes were time from initiation of CIIS to cessation of therapy, time to death for patients who did not receive surgical therapy and rates of involvement with palliative care. Results Overall, patients received CIIS therapy for an average of 5.9 months (standard deviation [SD] 7.3). Patients on CIIS as palliative therapy died in an average of 6.2 months (SD 6.6) from the time of initiation of CIIS, and those on CIIS as bridge therapy who did not ultimately receive surgical therapy died after an average of 8.6 months (SD 9.3). Patients who received CIIS as bridge therapy were significantly less likely to receive palliative-care consultation than those on inotropes as palliative therapy, whether or not they underwent surgery. Conclusions In this large cohort of patients with advanced HF, patients who on CIIS as palliative therapy survived for 6.2 months, on average, with wide variation among patients. Patients who were on CIIS as bridge therapy but did not ultimately receive surgical therapy received less palliative care despite the high mortality rate in this subgroup.

Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in prognostication after LVAD surgery has never been studied. VE/VCO2 slope is an important component of CPET which has direct pathophysiologic links to right ventricular (RV) performance. We hypothesized that VE/VCO2 slope would prognosticate RV dysfunction after LVAD. All CPET studies from a single institution were collected between September 2009 and February 2019. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2 and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic, echocardiographic and clinical markers of RV dysfunction as well mortality. Patients were stratified into those with a ventilatory class of III or greater. (VE/VCO2 slope of ≥ 36, n = 43) and those with a VE/VCO2 slope

Background Women differ from men in their left ventricular (LV) structure, function and remodeling with age and diseases. The LV assist device (LVAD) unloads the LV and reversely remodels the heart. We sought to define the effects of sex on longitudinal reverse remodeling after LVAD implantation. Methods and Results Cardiac structure and function were assessed by serial echocardiograms. Mixed effect regression models were constructed to assess the independent contribution of sex to longitudinal changes in cardiac structure and function. A total of 355 consecutive patients with advanced heart failure received continuous flow LVADs between 2006 and 2016. The average age was 56 ± 13 years, 73% were men, and 67% were black. Early (within 3 months) after LVAD implantation, women had a greater reduction in LV dimensions and a greater increase in LV ejection fraction compared with men. These differences were independent of age, body surface area, device type, or ischemic etiology of heart failure. At long-term follow-up, LV dimensions increased slightly over time in women compared with men, but overall, earlier changes were maintained. Conclusion Women had significantly more favorable longitudinal changes in cardiac structure and function in response to LV unloading compared with men. Understanding the cause of sex difference in reverse remodeling after LVAD may help to devise novel therapeutic strategies for women with advanced heart failure.

Noninvasive monitoring of heart allograft health is important to improve clinical outcomes. MicroRNAs (miRs) are promising biomarkers of cardiovascular disease and limited studies suggest they can be used to noninvasively diagnose acute heart transplant rejection.The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter prospective cohort study that phenotyped heart transplant patients from 5 mid-Atlantic centers. Patients who had no history of rejection after transplant were compared to patients with acute cellular rejection (ACR) or antibody-mediated rejection (AMR). Small RNA sequencing was performed on plasma samples collected at the time of an endomyocardial biopsy. Differential miR expression was performed with adjustment for clinical covariates. Regression was used to develop miR panels with high diagnostic accuracy for ACR and AMR. These panels were then validated in independent samples from GRAfT and Stanford University. Receiver operating characteristic curves were generated and area under the curve (AUC) statistics calculated. Distinct ACR and AMR clinical scores were developed to translate miR expression data for clinical use.The GRAfT cohort had a median age of 52 years, with 35% females and 45% Black patients. Between GRAfT and Stanford, we included 157 heart transplant patients: 108 controls and 49 with rejection (50 ACR and 38 AMR episodes). After differential miR expression and regression analysis, we identified 12 miRs that accurately discriminate ACR and 17 miRs in AMR. Independent validation of the miR panels within GRAfT led to an ACR AUC 0.92 (95% confidence interval [CI]: 0.86-0.98) and AMR AUC 0.82 (95% CI: 0.74-0.90). The externally validated ACR AUC was 0.72 (95% CI: 0.59-0.82). We developed distinct ACR and AMR miR clinical scores (range 0-100), a score ≥ 65, identified ACR with 86% sensitivity, 76% specificity, and 98% negative predictive value, for AMR score performance was 82%, 84% and 97%, respectively.We identified novel miRs that had excellent performance to noninvasively diagnose acute rejection after heart transplantation. Once rigorously validated, the unique clinical ACR and AMR scores usher in an era whereby genomic biomarkers can be used to screen and diagnose the subtype of rejection. These novel biomarkers may potentially alleviate the need for an endomyocardial biopsy while facilitating the initiation of targeted therapy based on the noninvasive diagnosis of ACR or AMR.

Continuous infusion of ambulatory inotropic therapy (AIT) is increasingly used in patients with end-stage heart failure (HF). There is a paucity of data concerning the concomitant use of beta-blockers (BB) in these patients.We retrospectively reviewed all patients discharged from our institution on AIT. The cohort was stratified into 2 groups based on BB use. The 2 groups were compared for differences in hospitalizations due to HF, ventricular arrhythmias and ICD therapies (shock or antitachycardia pacing).Between 2010 and 2017, 349 patients were discharged on AIT (95% on milrinone); 74% were males with a mean age of 61 ± 14 years. BB were used in 195 (56%) patients, whereas 154 (44%) did not receive these medications. Patients in the BB group had longer duration of AIT support compared to those in the non-BB group (141 [1-2114] vs 68 [1-690] days). After adjusting for differences in baseline characteristics and indication for AIT, patients in the BB group had significantly lower rates of hospitalizations due to HF (hazard ratio [HR] 0.61 (0.43-0.86); P = 0.005), ventricular arrhythmias (HR 0.34 [0.15-0.74]; P = 0.007) and ICD therapies (HR 0.24 [0.07-0.79]; P = 0.02).In patients with end-stage HF on AIT, the use of BB with inotropes was associated with fewer hospitalizations due to HF and fewer ventricular arrhythmias.

OBJECTIVES The influence of preoperative left ventricular size in outcomes following centrifugal-flow left ventricular assist device (LVAD) implantation has not been well characterized. METHODS A cohort of 313 patients who received a centrifugal-flow LVAD at a single institution was analysed. Using a maximally selected log-rank statistic, we investigated whether a left ventricular end-diastolic dimension (LVEDD) cut-off point was associated with worse outcomes. The cohort was then divided in 2 groups based on the LVEDD cut-off point. RESULTS An LVEDD cut-off point of 59 mm was found to predict worse survival. Smaller LVEDD patients (≤59 mm, N = 52) were older and more likely to have a history of coronary artery disease compared those with a larger LVEDD (>59 mm, N = 261). Smaller LVEDD patients had lower survival compared to larger LVEDD patients (71% vs 85% at 1 year and 58% vs 80% at 2 years, P = 0.003). The need for temporary right ventricular mechanical support was significantly higher in the smaller LVEDD cohort (11.5% vs 1.9%, P = 0.002). Pump flows at time of discharge were lower in the smaller LVEDD group (3.8 vs 4.2 l/min, P = 0.005), who also had a higher incidence of late right ventricular failure (23% vs 12%, P = 0.02), higher rates of gastrointestinal bleeding (0.416 vs 0.256 events per patient-year, P = 0.025) and higher readmissions secondary to low flow alarms (0.429 vs 0.240 events per patient-year, P = 0.007). Multivariable analysis demonstrated that smaller LVEDD, older age, high BUN and high bilirubin levels were independent predictors of worse survival. CONCLUSIONS In patients receiving a centrifugal-flow LVAD, smaller preoperative LVEDD (≤59 mm) was associated with lower survival and higher incidence of adverse outcomes.

Background COVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear. Methods We included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression , adjusting for age and time since transplant. Results The median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea , oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor , antimetabolite , and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR = 7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy . Conclusions We present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients.

Background: After heart transplantation, endomyocardial biopsy (EMBx) is used to monitor for acute rejection (AR). Unfortunately, EMBx is invasive, and its conventional histological interpretation has limitations. This is a validation study to assess the performance of a sensitive blood biomarker—percent donor-derived cell-free DNA (%ddcfDNA)—for detection of AR in cardiac transplant recipients. Methods: This multicenter, prospective cohort study recruited heart transplant subjects and collected plasma samples contemporaneously with EMBx for %ddcfDNA measurement by shotgun sequencing. Histopathology data were collected to define AR, its 2 phenotypes (acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), and controls without rejection. The primary analysis was to compare %ddcfDNA levels (median and interquartile range [IQR]) for AR, AMR, and ACR with controls and to determine %ddcfDNA test characteristics using receiver-operator characteristics analysis. Results: The study included 171 subjects with median posttransplant follow-up of 17.7 months (IQR, 12.1–23.6), with 1392 EMBx, and 1834 %ddcfDNA measures available for analysis. Median %ddcfDNA levels decayed after surgery to 0.13% (IQR, 0.03%–0.21%) by 28 days. Also, %ddcfDNA increased again with AR compared with control values (0.38% [IQR, 0.31–0.83%], versus 0.03% [IQR, 0.01–0.14%]; P Conclusions: We found that %ddcfDNA detected AR with a high area under the receiver operator characteristic curve and negative predictive value. Monitoring with ddcfDNA demonstrated excellent performance characteristics for both ACR and AMR and led to earlier detection than the EMBx-based monitoring. This study supports the use of %ddcfDNA to monitor for AR in patients with heart transplant and paves the way for a clinical utility study. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02423070.

The immune checkpoint inhibitors have brought about a paradigm shift in the treatment of many cancers and are being used as the first line therapy in increasing number of aggressive malignancies, including metastatic melanoma. Their adverse effects, mostly mediated by an uncontrolled overactivation of the immune system, may compromise the therapeutic benefit. Combination immune checkpoint therapies in particular, have higher therapeutic efficacy, but have also been associated with a higher incidence of severe immune-related adverse effects including autoimmune lymphocytic myocarditis. Recent clinical reports of this rare and life threatening condition indicated rapid progression of severe hemodynamic and electrical instability, with or without acute decompensated heart failure, reduced ejection fraction and shock, pointing to the need for early recognition, diagnosis and prompt management. Current guidelines for management of other immune-related adverse effects recommend high-dose glucocorticoids, with consideration of immunomodulators, such as infliximab in patients with severe colitis. However, knowledge about the treatment approaches in immune-related myocarditis remains extremely scarce. Here we report a case of severe, steroid refractory, lymphocytic myocarditis that occurred after the first cycle of combination immunotherapy with the programmed cell death protein-1 inhibitor, nivolumab, and the cytotoxic T-lymphocyte-associated protein 4 blocker, ipilimumab, for metastatic melanoma. We discuss treatment approaches including the role for transvenous pacemaker, advanced heart failure support, and interdisciplinary decision making.

Iatrogenic chordal rupture with severe mitral regurgitation is a rare but serious complication associated with the use of Impella device. We present a case of a 47-year-old man with ischemic cardiomyopathy who required insertion of an Impella 5.0 device. During Impella support, he developed acute pulmonary edema secondary to newly diagnosed posterior mitral valve chordal rupture and subsequent severe mitral regurgitation. He underwent implantation of a durable left ventricular assist device with concomitant edge-to-edge mitral valve repair through the apex.

Introduction Radiation therapy in patients with axial flow left ventricular assist devices (LVAD) has not been associated with significant device malfunction. However, the effects of radiation on the fully magnetically levitated HeartMate 3 (Abbott, Abbott Park, IL) LVAD are not well known. We report two cases of stereotactic bone radiation therapy (SBRT) in patients with a HeartMate 3 LVAD implantation. Case Report Patient 1 71-year-old woman with history of chronic systolic heart failure status post HeartMate 3 LVAD and history of left upper lobe non-small cell lung cancer status post lobectomy was found to have an incidental left lateral thorax wall mass on CT imaging with subsequent biopsy consistent for recurrent oligometastatic lung adenocarcinoma. She consequently underwent 5 fractions of 600 cGy SBRT to her left lateral chest wall over a period of 10 days. Mild fatigue was reported following radiation, however LVAD log files sent subsequent to each fraction were unremarkable. On follow up, no cardiac symptoms were reported and LVAD parameters were normal with flow 4.6 L/min, speed 5600 rpm, pulse index 2.8 and power 4.4 watts. Device malfunction has not been witnessed during 1 year follow up. Patient 2 70-year-old man with history of advanced systolic heart failure status post HeartMate 3 LVAD implantation was found to have a right upper lobe nodule and mediastinal lymphadenopathy on CT imaging. Ensuing biopsy diagnosed squamous cell lung cancer without metastatic disease. SBRT was initiated and 5 treatments of 1000 cGy were delivered to the right upper lobe lesion within 10 days. No LVAD complications or symptoms of heart failure were witnessed during treatment. On follow up, patient denied any symptoms and LVAD function remained normal with observed with flow 4.3 L/min, speed 5200 rpm, pulse index 4.8 and power 3.8 watts. Device malfunction has not been witnessed during 1 year follow up. Summary Our 2 cases suggests that SBRT in patients with HeartMate 3 LVAD implantation may be safe and likely not associated with device malfunction. Larger studies are required to better evaluate this relationship and to determine long term safety profile.

Purpose To evaluate early hemocompatibility-related outcomes after implementation of a low anti-Xa target heparin protocol following implantation of the HeartMate 3 Left Ventricular Assist Device (LVAD). Methods We reviewed hemocompatibility-related outcomes including mediastinal bleeding, gastrointestinal bleeding (GIB), stroke, and pump thrombosis (PT) events in recipients of HeartMate 3 LVADs before and after implementation of a low anti-Xa target heparin protocol. The higher anti-Xa protocol targeted levels of 0.3-0.5 IU/ml using a starting dose of 18 units/kg/hr with a maximum starting dose of 1530 units/hr, and the lower anti-Xa protocol targeted levels of 0.1-0.3 IU/ml using a starting dose of 7 units/kg/hr with a maximum starting dose of 595 units/hr. Results Between 9/2018 and 8/2020, 152 patients were implanted with a HeartMate 3. Mean patient age was 57 ± 12 years, 74% were males, and 76% of patients were African American. Per our center's protocol, IV heparin was started on postoperative day 5. 106 patients were treated with the higher anti-Xa protocol and 21 patients were treated with the lower anti-Xa protocol. The patients treated with the higher anti-Xa target protocol experienced 10 (9.4%) post-operative mediastinal bleeding events requiring return to the operating room (OR) while patients on the lower anti-Xa protocol experienced none. Patients treated with the higher anti-Xa target protocol experienced 8 (7.5%) GIB events within 60 days of implant while patients on the lower anti-Xa protocol experienced no GIB. Patients treated with the higher anti-Xa protocol experienced one hemorrhagic stroke and no ischemic strokes, while patients on the lower anti-Xa protocol experienced one ischemic stroke and no hemorrhagic strokes. No PT events requiring pump exchange occurred in either group. Conclusion Implementation of a low anti-Xa target heparin protocol after HeartMate 3 LVAD implantation surgery was associated with a lower incidence of mediastinal and GI bleeding. No PT events requiring pump exchange were observed in either group. Stroke rate was low in both groups. Further research is needed to determine the safest and most effective anticoagulation protocol after HeartMate 3 implantation that lowers the incidence of early hemocompatibility-related events.

Purpose Despite significant advances in US CV health, ethnic disparities in outcomes persist. The prognosis of HF among African-Americans (AA) is less favorable than other groups. The impact of race on durable LVAD outcomes is not well defined. We therefore sought to determine the characteristics and long term outcomes of AA LVAD recipients. Methods We performed a retrospective review of all LVAD recipients at a single center from October 1, 2006 to June 30, 2019. We compared clinical characteristics of AAs to non-AAs. Survival and rates of adverse events (AEs) for AA patients (pts) were determined. 571 pts were included in the analysis. Results 394 AA (69% of the population) underwent LVAD implantation. The mean follow up time of AA cohort was 670+617 days. The AA group was younger (54+13 vs 60+13, p Conclusion In the largest ever reported cohort of AA LVAD recipients, AA were shown to have excellent long term survival with rates of AEs comparable to those reported in published clinical trials. Further research is warranted to determine predictors of survival in AA pts.

Purpose Patients who suffer from device malfunction after axial-flow left ventricular assist device (af-LVAD) implantation often require device exchange. Although af-LVAD to af-LVAD exchange is reported as a safe procedure, rate of recurrent malfunction remains high. We hypothesized that af-LVAD to centrifugal-flow LVAD (cf-LVAD) exchange is associated with lower rate of recurrent malfunction requiring repeat exchange compared to af-LVAD to af-LVAD exchange. Methods We retrospectively reviewed all patients who underwent af-LVAD implantation between 5/2011 and 3/2019 at out institution. Of these, 31 patients underwent 43 device exchanges either to af-LVAD (AE group, N = 29) or to cf-LVAD (CE group, N = 14). Results Reasons of device exchange in the AE group were pump thrombosis in 19 (66 %), infection in 1 (3 %) and others in 9 (31 %), and those in the CE group were pump thrombosis in 8 (58 %), infection in 3 (21 %) and others in 3 (21 %). There was no difference in baseline characteristics between the groups except higher rate of more than mild aortic insufficiency in the CE group (CE; 50 % vs AE; 0 %, P Conclusion Af-LVAD to cf-LVAD exchange is a safe procedure for af-LVAD patients who require device exchange, and possibly decrease recurrent device malfunction event requiring repeat device exchange.

Purpose Higher rates of acute rejection in African American transplant recipients are reported across multiple organ types. Mechanisms underlying poorer outcomes vs. other races are poorly defined. Because race is a social construct, most studies use self-identified race to categorize patients. Reports of genetic unique to individuals of African ancestry (AA) led us to hypothesize that ancestry markers might enhance the precision of race categorization in studies of transplant injury and rejection. Methods Using the Genomic Research for Transplantation (GRAfT) cohort, we performed whole-genome genotyping assay and measured the donor-derived cell-free DNA (dd-cfDNA), a biomarker of graft injury. We genotyped 171 heart recipients and estimated the genetic ancestry proportions by GRAF-pop software referencing 1000Genome data. Applying the filters for African genetic ancestry proportion (AGAP), patients were categorized as AA if AGAP was > 85%, and not of AA if AGAP 15%. Serial post-transplant plasma samples were analyzed for dd-cfDNA by Illumina HiSeq3500. We consolidated the highest dd-cfDNA level along the time series to represent each individual; data are presented as median + the standard error. To assess potential relationship between AGAP and dd-cfDNA, we selected patients at two extremes: 31 AAs (>85% AGAP) and 97 non-AAs ( Results Among the 171 recipients, 69 self-reported as AAs (40%), while the AGAP reported 72 AAs (42 %). The consistence between self-reported and AGAP was 97.7% (167/171). AAs at the estimated extremes ( > 85% AGAP) had significantly higher dd-cfDNA level than non-AAs ( 15% AGAP): 3.64 + 0.73 vs. 1.79 + 0.41, p=0.03). Self-reported race showed a non-significant trend towards higher dd-cfDNA levels in AAs compared to non-AAs: 2.91 + 0.48 vs. 1.79 + 0.40, p=0.074). Conclusion This study documents a high consistence between self-reported race and genetic ancestry markers. It also confirms our prior reports of increased graft injury reflected as higher levels of dd-cfDNA in AAs at the extremes of genetic ancestry proportion. Supporting our hypothesis, ancestry markers might augment self-reported race data, warranting further studies on the interaction genetic heterogeneity with social determinants of health.

Purpose Despite the approval of LVADs as destination therapy (DT) nearly 2 decades ago, significant knowledge gaps remain regarding the characteristics and outcomes of AA patients (pts) who receive LVAD therapy as DT. The present analysis sought to assess the characteristics and outcomes of DT LVAD AA pts. Methods Single center retrospective review of DT LVAD pts from 1/1/2009 to 12/31/2019 was performed. We compared clinical characteristics of AAs to non-AAs. Survival and hemocompatibility-related adverse event (HRAE) rates for AA pts were determined. Uni- and multivariate predictors of mortality were identified. Results 256 pts underwent DT LVAD implantation, of which 180 (70%) were AA. 63 pts received a HMII, 54 HVAD, and 63 HM3. Compared to non-AAs, AA pts were younger (AA: 57 ± 12 vs non-AA: 67 ± 9), more likely to be female (33% vs 16%) have HTN (71% vs 57%), had a higher BMI (mean BMI 30 ± 8 vs 26 ± 5), a non-ischemic cardiomyopathy (76% vs 33%), and a history of stroke/TIA (19% vs 8%). There were no significant differences between the 2 groups in terms of INTERMACS profile. Post-operatively, the AA cohort required more days of vasopressor support (9.5 ± 14 vs. 6.0 ± 6) and had a higher postoperative length of stay (32.9 ± 21.0 vs. 26.2 ± 21.9 days). Among AAs, GI bleeding was the most common HRAE (44% of patients with events per patient year, EPPY 0.55) followed by stroke (22%, EPPY 0.13) and pump thrombosis (16%, EPPY 0.13). The HM3 was associated with lowest HRAE rates (EPPY) amongst the 3 devices (GIB 0.40, stroke 0.07, and no pump thrombosis events). Overall survival among AA DT pts was 81% and 69% at 1-year and 2-years. 5-year survival was 41%. On univariate analysis, history of prior sternotomy (HR 1.93, 95% CI 1.03-3.59, p=0.04) and total bilirubin (HR 1.21, 95% CI 1.04-1.40, p=0.01) were predictors of AA mortality while INTERMACS profile ≥3 (HR 0.67, 95% CI 0.49-0.93, p=0.02) was associated with improved survival. Total bilirubin was the only independent predictor of mortality in multivariate analysis (HR 1.18, 95% CI 1.0-1.4, p=0.05). Conclusion AA DT LVAD pts experienced excellent 1- and 2-year survival comparable to those demonstrated in large clinical studies. HM3 implantation was associated with lower rates of GIB, pump thrombosis, and stroke. Future research focused on barriers to LVAD therapy and the quality of life of AA LVAD pts is warranted.

Purpose Continuous infusion of inotropes is increasingly used in patients with end-stage heart failure who are being discharged from the hospital. However, Dobutamine and Milrinone are both known to be arrhythmogenic agents. Because Milrinone does not act through the beta-adrenergic system, it may allow for the cautious addition of beta-blockers (BB). We therefore sought to compare the impact of BB use is these patients on ventricular arrhythmias. Methods We retrospectively reviewed all patients who were discharged from our Institution on inotropes (used as a bridge to durable LVAD or transplant, as a bridge to recovery, or as a palliative measure). The cohort was stratified into 2 groups based on whether BB were added to the medical regimen. We compared the incidence of ventricular arrhythmias and ICD device therapy (defined as shock or anti-tachycardia pacing) between the 2 groups. Results Between 2010 and 2017, 349 patients were discharged on inotropes. Mean age was 61+14 years, 74% were men and 64% were African American. Most patients (330) were treated with Milrinone. BB were used in 195 (56%) of patients, whereas 154 (44%) did not receive these meds. There were no significant differences between the 2 groups in baseline socio-demographics, etiology of cardiomyopathy, CV comorbidities, or invasive hemodynamics. Patients on BB were more likely to receive an LVAD/transplant (49% vs. 41%) or be weaned off inotropes (12% vs. 4%), and less likely to transition to hospice care/death (37% vs 53%). Patients on BB were more likely to receive ACEI/ARB than those who were not on BB (67% vs. 47%, p Conclusion In heart failure patients who are discharged on inotropes, the use of BB appears to be associated with a lower incidence of sustained ventricular arrhythmias, ICD shocks or anti-tachycardia pacing. Prospective studies are warranted to confirm these findings.

Cobalt toxicity is a rare cause of infiltrative cardiomyopathy. We describe a case of cobalt-induced cardiomyopathy that progressed to end stage heart failure requiring orthotopic heart transplantation. A 67 year old woman with history of bilateral cobalt-chromium hip replacements presented with dyspnea of 3 weeks duration. She was tachycardic and hypotensive, with elevated NT- proBNP. Electrocardiogram demonstrated sinus tachycardia, low voltage and right bundle branch block. Transthoracic echocardiogram revealed left ventricular ejection fraction of 20-25% with global hypokinesis and a moderate circumferential pericardial effusion. Left and right heart catheterization showed normal coronaries, elevated filling pressures and low cardiac index. Dobutamine infusion was initiated for management of cardiogenic shock. Cardiac magnetic resonance imaging (MRI) illustrated diffuse late gadolinium enhancement concerning for infiltrative cardiomyopathy. Extensive non-ischemic and rheumatologic workup was negative. Cobalt and chromium levels were significantly elevated at 121 mcg/L (Nl

Purpose A thoracotomy approach for left ventricular assist device implantation is theoretically beneficial in patients who had previous sternotomy. The aim of this study is to investigate short-term outcomes of a thoracotomy approach versus a re-do sternotomy approach for left ventricular assist device implantation in patients with previous sternotomy. Methods We retrospectively reviewed 227 patients who underwent left ventricular assist device (HeartWare, HVAD) implantation between 7/2011 and 1/2019. Of these, 52 had a previous sternotomy. Twenty-eight patients were excluded because they had an extracorporeal ventricular assist device, cardiac surgery during the same hospitalization, concomitant procedures or an alternative outflow graft anastomosis at the time of the implantation. The study cohort was divided in two groups based on incision approach: a left anterior thoracotomy approach (LAT group, N=14) and a re-do sternotomy approach (RS group, N=10). Results Previous cardiac surgeries of the cohort were coronary artery bypass grafting (CABG) in 16 patients, aortic valve replacement (AVR) in 1, mitral valve (MV) replacement in 1, MV repair in 1, CABG + AVR in 1, CABG + MV repair in 1, atrial septal defect closure in 2, and heart transplant in 1. There was no difference in baseline characteristics between the groups. Median cardiopulmonary bypass time was similar, though median operative time in the LAT group was longer than that in the RS group (LAT; 267 mins vs RS; 235 mins). There was no statistical difference in postoperative short-term outcomes between the groups, except the LAT group required less postoperative red blood cell transfusion compared to the RS group (LAT; 57 % vs RS; 100 %, P = 0.024). Conclusion A thoracotomy approach was feasible alternative in patients with previous cardiac surgery and associated with less blood transfusion requirement compared with a re-do sternotomy approach.

Purpose Excellent outcomes following HM3 LVAD implantation have been reported in the setting of a large multicenter randomized controlled trial. Real world experience reports with this device are still limited. We sought to review our experience with this fully magnetically levitated LVAD. Methods The first 125 consecutive patients who received a HM3 LVAD at our institution from October 1, 2015 to August 30, 2019 were analyzed. Pump exchange procedures were excluded. We investigated clinical outcomes including survival and the development of postoperative complications. Results All devices were implanted via median sternotomy. Mean patient age was 57.5 ± 11 years, 72 % were males and 74% African-Americans. Idiopathic dilated cardiomyopathy was the most common diagnosis (73%). 67 % of the patients were INTERMACS profiles 1 or 2. 19 % of devices were implanted as bridge to transplant and 59% as destination therapy. Mean body-mass index at the time of implant was 30.5 ± 8 Kg/m2. Mean creatinine level was 1.29 ± 0.4 mg/dl and mean bilirubin was 1.45 ± 1.6 mg/dl. The mean length of stay during index admission for LVAD was 30 ± 17 days and the mean follow-up time was 411 ± 34 days. The rate of complications measured as EPPY was 0.42 for GI bleeding, 0.03 for ischemic stroke, 0.01 for hemorrhagic stroke, 0 for clinically suspected pump thrombosis or confirmed pump thrombosis, 0.22 for LVAD related infection, 0.16 for other systemic infection and 0.59 for acute heart failure. Survival was estimated at 96%, 91%, 88%, 81% and 74% at 30-day, 90-day, 1-year, 2-year, and overall 3-year follow-up, respectively (Figure). Conclusion In this single center, real world experience, HeartMate 3 implantation was associated with excellent survival comparable to those demonstrated in a recent clinical trial. The incidence of complications was also low, including no episodes of suspected or confirmed pump thrombosis.

Purpose The HeartMate 3 (HM3) LVAD has demonstrated the lowest rates of hemocompatibility adverse events (AEs) in randomized controlled trials. Despite this success, rate of bleeding remains high. HM3 instruction for use recommends starting parenteral heparin 12-24 hours after device implantation or when chest tube drainage is 2 days post implant). The aim of the study is to evaluate the association of thrombotic and hemorrhagic events with delayed heparin initiation in HM3 recipients Methods We performed a retrospective analysis of all HM3 patients implanted at a single center from Oct 1, 2015 to Jun 30, 2019. Patients who received IV heparin ≤2 days after implant were excluded from the analysis (n=6) Results 113 patients were included in the analysis. Mean follow up time was 382±331 days. Mean age was 57±12 years. The cohort was predominantly men (72%), African-American (77%) with a NICM etiology (74%). HM3 implantation as DT represented 54% of the population (BTT 26%). 18% of patients had a history of CVA pre-implant, 2% had history of GIB. The mean time to heparin initiation was 5±2 days. Mean time to warfarin and ASA initiation was 11±9 and 2+6 days respectively. The rates of neurologic event, and hemorrhagic/ischemic CVAs were numerically similar to the rates seen in clinical trials. No confirmed pump thrombosis event was seen. The rate of GI bleeding was higher than seen in trials. Overall, the survival of this cohort was 88% and 84% at 1 and 2 years, respectively Conclusion In this single center study, a strategy of delayed heparin initiation post HM3 implantation does not appear to increase the risk of CVA or pump thrombosis. A prospective clinical study is warranted.

Purpose Outcomes of patients with small body size following HM3 LVAD implantation have not been well characterized. We sought to compare preoperative characteristics and clinical outcomes among patients stratified by body surface area. Methods Patients who received a HeartMate 3 LVAD at our institution between October 1, 2015 and June 30, 2019 were analyzed. Patients who received a HM3 LVAD as pump exchange were excluded. The cohort was divided in 4 groups: BSA ≤1.8 m2 (group 1), BSA >1.8 - ≤2.0 m2 (group 2), BSA >2.0 - ≤2.2 m2 (group 3) and BSA >2.2 (group 4). Results One hundred and nineteen patients were included in this analysis. Preoperative characteristics and postoperative results of each group are shown in Table 1. Group 1 patients were older and mostly females. A history of diabetes was less common in this group. Mean postoperative length of stay was similar between groups. Pump speed at the time of discharge was lower in group 1 patients. Mean follow-up was similar between groups. Mean days out of the hospital after discharge did not differ among the groups. One-year survival was 93% for group 1, 85% for group 2, 86% for group 3 and 84% for group 4 (p=0.69). Kaplan Meier survival curves are shown in Figure 1 (log rank: 0.692). Conclusion Outcomes following HM3 LVAD implantation were comparable between patients with small body surface area and patients with larger body size. Small body size should not be an exclusion criteria for HM3 LVAD implantation in patients with advanced heart failure who are otherwise candidates for durable mechanical support.

Purpose Outcomes in patients with small left ventricular end diastolic diameter (LVEDD) following HM3 LVAD implantation have not been well characterized. We sought to compare the clinical outcomes of patients with small LVEDD to those with dilated left ventricles. Methods Patients who received a HeartMate 3 LVAD at our institution between October 1, 2015 and June 30, 2019 were analyzed. Patients who received a HM3 LVAD as a pump exchange were excluded. The cohort was divided in 2 groups: smaller LVEDD (≤60 mm in males and ≤58 mm in females) and larger LVEDD (>60 mm in males and >58 mm in females). Results One hundred and nineteen patients underwent HeartMate 3 LVAD implantation at our institution. Patients in the smaller LVEDD group (n: 22) had a mean LVEDD of 55.7±5 mm and patients in the larger LVEDD group had a mean LVEDD of 70.6±8 mm (p= Conclusion Adult patients with smaller LVEDD who received a HeartMate 3 LVAD have comparable clinical outcomes to patients with larger LVEDD. A small left ventricle should not be a contraindication to implantation of this particular durable device in adult patients.

Purpose Cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies but its role in prognostication after LVAD surgery has never been studies. Methods All CPET studies from a single institution were collected between September 2007 and March 2018. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2, and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic and clinical markers of RV dysfunction as well mortality. Results 449 patients underwent CPET testing. 120 patients were ultimately referred to the advanced heart failure program and 61 patients later received LVAD implantation (18 axial flow, 43 centrifugal flow, 70% male). CPET testing occurred 554 ± 624 days before LVAD and RHC occurred 232 ± 243 days after LVAD. Patients with a ventilatory class of III or greater (VE/VCO2 slope of ≥ 36, n = 38) had greater rates of death (21% vs. 0%, p = 0.02) than patients with VE/VCO2 slope Conclusion Elevated preoperative VE/VCO2 slope is a predictor of post-operative mortality and is associated with post-operative hemodynamic markers of impaired RV performance.

Summary of Objectives Genomic biomarkers are used to non-invasively screen cardiac transplant recipients for allograft rejection. Gene expression profiling has no ability to diagnose antibody-mediated rejection (AMR) and has a poor positive predictive value for T-cell mediated rejection (TCMR). An emerging class of genomic biomarkers are circulating, cell-free microRNAs (cf-miR). MicroRNAs modulate gene expression and have been implicated in rejection, they are found in the circulation, and early studies, using targeted genomic approaches suggest that cf-miRs may be a helpful biomarker to detect rejection. We hypothesize that cf-miRs can non-invasively diagnose rejection and distinguish AMR from TCMR. Methods The Genomic Research Alliance for Transplantation (GRAfT) is a prospective, multicenter study enrolling transplant recipients since 2014. All patients with AMR or TCMR were included and a group of controls without rejection were selected based on age, sex and race. Each biopsy was reviewed by two blinded, independent, expert cardiac pathologists. Plasma aliquots will undergo small molecular RNA isolation and the circulating cf-miR transcriptome will be sequenced using a next-generation platform. We expect to generate ∼6 million, single-end, 50bp reads per sample. Sequence data will be annotated using the FASTX_Toolkit and DESeq2 will be used to identify differentially expressed cf-miRs. Machine learning algorithms will be used to refine the cf-miR panel and maximize the C-statistic. Endpoints The study includes 35 patients with allograft rejection and 70 controls (Table). For the TCMR cohort there were 27 episodes of grade ≥ 2R rejection. For AMR there are 11 episodes of ≥ pAMR2 and 16 episodes of pAMR1 h or i. In total ∼300 plasma samples will be sequenced. Our primary objective is to develop a cf-miR panel that diagnoses allograft rejections, distinguishes rejection subtypes and allows for a blood-based, biochemical assessment of rejection severity.

Purpose Advanced kidney disease is often considered a relative contraindication to LVAD implantation and many implanting centers view stage 4 and 5 chronic kidney disease (CKD) as an absolute contraindication. We sought to analyze the impact of CKD at the time of LVAD implant on outcomes. Methods All LVAD patients between September 2007 and September 2017 with CKD at the time of LVAD implantation from a single institution were analyzed. Patients were stratified by CKD stage (CKD 1 through 5) at the time of implant and rates of worsening renal function, need for renal replacement therapy (RRT), hospitalizations, LVAD-related complications and death were analyzed. Results Of the 405 total patients, 191 patients (59% centrifugal, 80% male, average age 59 ± 11 years) had varying degrees of renal dysfunction at the time of LVAD implantation (17% CKD 1 or 2, 35% CKD 3a, 34% CKD 3b and 15% CKD 4 or 5). Patients with CKD 4 or 5 were more likely to require RRT than lesser CKD Stages 3b, 3a, and 1 or 2 (37.9% vs. 3.1%, vs. 7.6% vs. 0%, p trend Conclusion Patients with advanced CKD at the time of LVAD implant were more likely to have persistent renal dysfunction and require RRT thereafter. However, there were no statistically significantly differences in LVAD-related morbidity and mortality across the stages of CKD.

Purpose Advanced renal dysfunction is often viewed as a relative contraindication to durable left ventricular assist device (LVAD) implantation. We investigated the impact of early renal recovery on clinical outcomes after LVAD implantation. Methods All patients with baseline renal dysfunction who were implanted with a durable LVAD between September 2007 and September 2017 from a single institution were studied. Glomerular filtration rates at time of LVAD implant, 1 week, 1 month and 6 months after implant were collected. Early renal improvement was defined as an increase in eGFR of ≥ 15% within 1 week of implant (ΔGFR≥15%). Outcomes collected included index hospitalization length of stay (LOS), LVAD-related complications, hospitalizations and death. Results 405 patients were implanted with durable LVADs, of which, 191 patients (average age 59 years, 80% male, 73% African American, 46% bridge to transplant, 59% centrifugal) had varying degrees of renal dysfunction at implantation (17% CKD 1 or 2, 35% CKD 3a, 33% CKD 3b and 15% CKD 4 or 5). 68% of patients experienced ΔGFR≥15%. African American ethnicity and obesity (BMI 31.6 ± 6.9 vs. 28.7 ± 6.9, p =0.01) was associated with less renal improvement compared with their counterparts. Patients with ΔGFR≥15% were more likely to be CKD stage 1 or 2 six months after LVAD implant (53% vs. 22%, p = 0.005) (figure top). Index hospitalization LOS (39 ± 21 vs. 50 ± 32 days, p =0.02) was lower in patients with ΔGFR≥15% with fewer percutaneous endoscopic gastrostomy tube placement (4% vs. 15%, p = 0.02) and tracheostomy (6% vs 13%, p = 0.14). Patients with ΔGFR≥15% also had fewer heart failure readmissions (12% vs. 24%, p Conclusion Early improvement in renal function is associated with sustained renal recovery, decreased length of stay, fewer complications at index hospitalization and reduced heart failure readmissions.

Cardiac sarcoidosis has a wide range of manifestations. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan and cardiac magnetic resonance imaging (CMR) are the two major diagnostic modalities for cardiac sarcoidosis, but may not detect isolated conduction system involvement. A 55 year

Background: Prehospital 12-lead electrocardiogram (ECG) reduces the time to reperfusion in acute ST-segment elevation myocardial infarction (STEMI). However, the reliability of using cellular video-phone (VP) assisted interpretation of ECG is unknown. Methods: We studied the interphysician reliability in interpreting the ECG assisted with VP compared to print ECG interpretation. Twenty-seven physicians prospectively interpreted the ECG transmitted from the field in real-time using VP and later using the same printed ECG. The time to completion, accuracy of interpretation, and physician rating of the VP technology were recorded. Results: Similar high interphysician reliability was observed with both VP assisted and printed ECG interpretation including presence of ST-segment elevation (intraclass correlation coefficient [ICC]= 0.98 [95% CI 0.96–1] vs. 0.99 [95% CI 0.99–1]) and pathologic Q wave (ICC = 0.99 [95% CI 0.98–1] vs. 1 [95% CI 1]), respectively. The mean time to transmit and interpret the ECG with VP versus printed ECG was 3.9 ± 1.9 versus 2.1 ± 0.9 minutes, respectively, P < 0.01. On a scale of 1 to 5 with 5 being the best, the average rating of VP ease of use was 4.4 ± 0.5 and utility to recommend treatment was rated a 5. Conclusion: Cellular VP-assisted transmission and interpretation in real-time of prehospital ECG has high interphysician reliability, similar to the printed ECG interpretation. Future studies testing whether VP decreases the ischemic time and expedites the reperfusion of STEMI patients are needed. (J Interven Cardiol 2011;24:112–118)