Showing papers by "Sean Pinney published in 2022"

Donor heart selection: Evidence-based guidelines for providers.

Abstract: The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review.

Management of Heart Failure.

Abstract: This JAMA Clinical Guidelines Synopsis summarizes the 2022 ACC/AHA/HFSA guidelines for management of heart failure in adults with a diagnosis of or at risk for heart failure.

Sodium Glucose Co-Transporter 2 Inhibitor Use in Patients with Left Ventricular Assist Devices

Abstract: Purpose Multiple studies have shown improved cardiovascular outcomes with a sodium glucose-co-transporter 2 inhibitor (SGLT2i) in patients with heart failure with reduced ejection fraction (HFrEF). There are no current data supporting safety or efficacy in the Left Ventricular Assist Device (LVAD) population. The purpose of this study is to assess use of SGLT2 inhibitors in LVAD patients. Methods A retrospective analysis of LVAD patients implanted since 2015 was completed. Patients prescribed SGLT2i were identified. Clinical and laboratory variables were assessed following SGLT2i initiation with median values calculated at three and six month intervals. Results A total of 15 patients were prescribed SGLT2i, dapagliflozin (n=10) or empagliflozin (n=5), following LVAD implantation with follow-up time of 8 months (IQR 7-11). Six patients were naïve to SGLT2i until after implant, with 9 re-started on their pre-implant SGLT2i. Ten of the 15 carry a diagnosis of Diabetes Mellitus. Mean arterial pressure was 87 mmHg (IQR 82-88, n=15) at initiation, 78 mm Hg (IQR 74-89, n=15) at three months, and 82 mmHg (IQR 73-91, n=13) at six months. Estimated glomerular filtration rate was 70 mL/min/1.73m2 (IQR 54-92, n=15) at initiation, 79.5 mL/min/1.73m2 (IQR 60-94, n=12) at three months, and 74 mL/min/1.73m2 (IQR 62-78, n=9) at six months. Pro-brain natriuretic peptide decreased from 2005 pg/mL (IQR 1208-3813, n=13) at initiation, to 1334 pg/mL at 3 months (IQR 876-3617, n=11), and 885 pg/mL (IQR 409-1164, n=8) at 6 months. Glycated hemoglobin at the time of initiation was 7.4% (IQR 6.4-7.9, n=12), 7% (IQR 6.8-8.2, n=9) at 3 months, and 6.8% (IQR 6.5-7.3, n=6) at 6 months. One of the 15 patients had SGLT2i therapy discontinued due to recurrent genital yeast infections. Eight of the 15 patients had 11 total unplanned hospitalizations due to: gastrointestinal bleeding (2), acute decompensated heart failure (5), driveline infection (1), arrhythmia (1), drug-related reaction (1), diabetic ketoacidosis (DKA) (1). The hospitalization for DKA occurred while receiving high-dose steroids, and SGLT2i was resumed without adverse effects. Conclusion SGLT2i were successfully initiated in a small cohort of LVAD patients without significant adverse events. Larger, prospective studies are needed to determine if the cardiovascular and renal benefits of SGLT2i carry over from HFrEF to LVAD patients. Multiple studies have shown improved cardiovascular outcomes with a sodium glucose-co-transporter 2 inhibitor (SGLT2i) in patients with heart failure with reduced ejection fraction (HFrEF). There are no current data supporting safety or efficacy in the Left Ventricular Assist Device (LVAD) population. The purpose of this study is to assess use of SGLT2 inhibitors in LVAD patients. A retrospective analysis of LVAD patients implanted since 2015 was completed. Patients prescribed SGLT2i were identified. Clinical and laboratory variables were assessed following SGLT2i initiation with median values calculated at three and six month intervals. A total of 15 patients were prescribed SGLT2i, dapagliflozin (n=10) or empagliflozin (n=5), following LVAD implantation with follow-up time of 8 months (IQR 7-11). Six patients were naïve to SGLT2i until after implant, with 9 re-started on their pre-implant SGLT2i. Ten of the 15 carry a diagnosis of Diabetes Mellitus. Mean arterial pressure was 87 mmHg (IQR 82-88, n=15) at initiation, 78 mm Hg (IQR 74-89, n=15) at three months, and 82 mmHg (IQR 73-91, n=13) at six months. Estimated glomerular filtration rate was 70 mL/min/1.73m2 (IQR 54-92, n=15) at initiation, 79.5 mL/min/1.73m2 (IQR 60-94, n=12) at three months, and 74 mL/min/1.73m2 (IQR 62-78, n=9) at six months. Pro-brain natriuretic peptide decreased from 2005 pg/mL (IQR 1208-3813, n=13) at initiation, to 1334 pg/mL at 3 months (IQR 876-3617, n=11), and 885 pg/mL (IQR 409-1164, n=8) at 6 months. Glycated hemoglobin at the time of initiation was 7.4% (IQR 6.4-7.9, n=12), 7% (IQR 6.8-8.2, n=9) at 3 months, and 6.8% (IQR 6.5-7.3, n=6) at 6 months. One of the 15 patients had SGLT2i therapy discontinued due to recurrent genital yeast infections. Eight of the 15 patients had 11 total unplanned hospitalizations due to: gastrointestinal bleeding (2), acute decompensated heart failure (5), driveline infection (1), arrhythmia (1), drug-related reaction (1), diabetic ketoacidosis (DKA) (1). The hospitalization for DKA occurred while receiving high-dose steroids, and SGLT2i was resumed without adverse effects. SGLT2i were successfully initiated in a small cohort of LVAD patients without significant adverse events. Larger, prospective studies are needed to determine if the cardiovascular and renal benefits of SGLT2i carry over from HFrEF to LVAD patients.

Enhancing Palliative Care for Patients With Advanced Heart Failure Through Simple Prognostication Tools: A Comparison of the Surprise Question, the Number of Previous Heart Failure Hospitalizations, and the Seattle Heart Failure Model for Predicting 1-Year Survival

Abstract: Background Score-based survival prediction in patients with advanced heart failure (HF) is complicated. Easy-to-use prognostication tools could inform clinical decision-making and palliative care delivery. Objective To compare the prognostic utility of the Seattle HF model (SHFM), the surprise question (SQ), and the number of HF hospitalizations (NoH) within the last 12 months for predicting 1-year survival in patients with advanced HF. Methods We retrospectively analyzed data from a cluster-randomized controlled trial of advanced HF patients, predominantly with reduced ejection fraction. Primary outcome was the prognostic discrimination of SHFM, SQ (“Would you be surprised if this patient were to die within 1 year?”) answered by HF cardiologists, and NoH, assessed by receiver operating characteristic (ROC) curve analysis. Optimal cut-offs were calculated using Youden’s index (SHFM: <86% predicted 1-year survival; NoH ≥ 2). Results Of 535 subjects, 82 (15.3%) had died after 1-year of follow-up. SHFM, SQ, and NoH yielded a similar area under the ROC curve [SHFM: 0.65 (0.60–0.71 95% CI); SQ: 0.58 (0.54–0.63 95% CI); NoH: 0.56 (0.50–0.62 95% CI)] and similar sensitivity [SHFM: 0.76 (0.65–0.84 95% CI); SQ: 0.84 (0.74–0.91 95% CI); NoH: 0.56 (0.45–0.67 95% CI)]. As compared to SHFM, SQ had lower specificity [SQ: 0.33 (0.28–0.37 95% CI) vs. SHFM: 0.55 (0.50–0.60 95% CI)] while NoH had similar specificity [0.56 (0.51–0.61 95% CI)]. SQ combined with NoH showed significantly higher specificity [0.68 (0.64–0.73 95% CI)]. Conclusion SQ and NoH yielded comparable utility to SHFM for 1-year survival prediction among advanced HF patients, are easy-to-use and could inform bedside decision-making.

Heart Mate 3 Pump Thrombosis After Ventricular Tachycardia Ablation: Pushing the Boundaries of Hemocompatibility

Abstract:

Introduction

The risk for pump thrombosis (PT) following ventricular tachycardia (VT) ablation in HeartMate II and HeartWare HVAD left ventricular assist devices (LVADs) has been described previously; however, it is unknown whether Heart Mate 3 (HM3) LVADs are also at increased risk of PT following VT ablation.

Case Report

A 51-year-old male with non-ischemic cardiomyopathy status post HM3 LVAD as destination therapy, VT on mexiletine and quinidine with previous VT ablation, and amiodarone-induced thyrotoxicosis presented to the emergency room in VT storm after multiple defibrillator shocks. He underwent successful endocardial/epicardial VT ablation of seven VT morphologies, ethanol ablation of the coronary sinus branch, as well as coil embolization of two left circumflex branches that fed the culprit territory. Target ACT was achieved throughout the procedure and he was bridged to warfarin with a therapeutic INR upon discharge. Two weeks later, he presented with low flow LVAD alarms, a subtherapeutic INR, and an elevated lactate dehydrogenase concerning for PT. Despite volume resuscitation and pressors, he required initiation of venoarterial extracorporeal membrane oxygenation (VA-ECMO), intra-aortic balloon pump, and underwent a LV outflow tract aortogram. Thrombus was noted in the LVAD outflow graft and the LVAD flow was 0 liters per minute. Thrombolytics were not given due to the patient's tenuous status and need for emergent pump exchange, so decision was made to turn off the LVAD to prevent a cardioembolic event while he was supported by VA-ECMO. Transthoracic echocardiogram confirmed PT with a large thrombus extending out of the inflow cannula. The patient was deemed not to be a surgical candidate given a high operative mortality after worsening shock, liver failure, and bacteremia. His family proceeded with comfort care and support was withdrawn.

Summary

While PT is rare with HM3 LVADs even with lower intensity anticoagulation, there may be a higher risk of PT after VT ablation.

The Sleeping Giant Awakes: A Case of Recurrent Post-Transplant Giant Cell Myocarditis

Abstract: Introduction A 69-year-old man with no past medical history was admitted with acute-onset heart failure with rapid progression to cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation. He underwent urgent heart transplantation (HT) within one week of listing. Case Report He received immunosuppression with methylprednisolone, mycophenolate, and tacrolimus. Retrospective crossmatch was negative. The explanted heart showed diffuse giant cell myocarditis (GCM) (Figures A-C) One week after transplant he had normal biventricular filling pressures with preserved cardiac output and a Grade 0 endomyocardial biopsy (EMB). During his second post-operative week, he developed paroxysmal atrial fibrillation, for which flecainide 50 mg twice daily was initiated. Two weeks post-transplant he had normal hemodynamics, but three of four EMB samples showed multinucleated giant cells (Figure D). Cardiac magnetic resonance (CMR) imaging was done at the time of diagnosis and was notable for non-specific diffuse late gadolinium enhancement throughout the left ventricular myocardium which “could be related to recent history of heart transplant or a diffuse infiltrative process.” He was treated with a three-day course of IV methylprednisolone, one gram daily, followed by an oral steroid taper. Mycophenolate was increased from 1000 mg to 1500 mg twice daily. Tacrolimus goal remained at 10-12 [units]. EMB three- and four-weeks post-transplant did not show any evidence of GCM. Serial surveillance EMB have not shown any further recurrence of GCM throughout the first post-transplant year. Additionally, repeat CMR one- and six-months after initial imaging showed resolution of all abnormalities. Prednisone 5 mg daily will be continued indefinitely due to his GCM history. Summary A 69-year-old man with GCM requiring urgent HT was noted to have recurrence of GCM two weeks after transplant. Following a three-day steroid pulse, the patient did not have any further recurrence of GCM during the first transplant year. A 69-year-old man with no past medical history was admitted with acute-onset heart failure with rapid progression to cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation. He underwent urgent heart transplantation (HT) within one week of listing. He received immunosuppression with methylprednisolone, mycophenolate, and tacrolimus. Retrospective crossmatch was negative. The explanted heart showed diffuse giant cell myocarditis (GCM) (Figures A-C) One week after transplant he had normal biventricular filling pressures with preserved cardiac output and a Grade 0 endomyocardial biopsy (EMB). During his second post-operative week, he developed paroxysmal atrial fibrillation, for which flecainide 50 mg twice daily was initiated. Two weeks post-transplant he had normal hemodynamics, but three of four EMB samples showed multinucleated giant cells (Figure D). Cardiac magnetic resonance (CMR) imaging was done at the time of diagnosis and was notable for non-specific diffuse late gadolinium enhancement throughout the left ventricular myocardium which “could be related to recent history of heart transplant or a diffuse infiltrative process.” He was treated with a three-day course of IV methylprednisolone, one gram daily, followed by an oral steroid taper. Mycophenolate was increased from 1000 mg to 1500 mg twice daily. Tacrolimus goal remained at 10-12 [units]. EMB three- and four-weeks post-transplant did not show any evidence of GCM. Serial surveillance EMB have not shown any further recurrence of GCM throughout the first post-transplant year. Additionally, repeat CMR one- and six-months after initial imaging showed resolution of all abnormalities. Prednisone 5 mg daily will be continued indefinitely due to his GCM history. A 69-year-old man with GCM requiring urgent HT was noted to have recurrence of GCM two weeks after transplant. Following a three-day steroid pulse, the patient did not have any further recurrence of GCM during the first transplant year.

The prognostic role of advanced hemodynamic variables in patients with left ventricular assist devices

Abstract: Background: Invasive hemodynamic variables obtained from right heart catheterization have been used for risk-stratifying patients with advanced heart failure. However, there is a paucity of data on the prognostic value of invasive hemodynamic variables in patients with left ventricular assist devices (LVAD). We hypothesized that cardiac power output (CPO), cardiac power efficiency (CPE), and left ventricular stroke work index (LVSWI) can serve as prognostic markers in patients with LVADs. Methods: Baseline hemodynamic data from patients who had LVAD ramp studies at our institution from 4/2014 to 7/2018 were prospectively collected, from which advanced hemodynamic variables (CPO, CPE, and LVSWI) were retrospectively analyzed. Univariate and multivariable analyses were performed for hemocompatibility-related adverse events (HRAE), HF admissions, and mortality. Results: Ninety-one participants (age 61 ± 11 years, 34% women, 40% Black or African American, and 38% ischemic cardiomyopathy) were analyzed. Low CPE was significantly associated with mortality (HR 2.42, 95% CI 1.02–5.74, p = 0.045) in univariate analysis and Kaplan–Meier analysis (p = 0.04). Low LVSWI was significantly associated with mortality (HR 2.13, 95% CI 1.09–4.17, p = 0.03) in univariate analysis and Kaplan–Meier analysis (p = 0.02). CPO was not associated with mortality. CPO, CPE, and LVSWI were not associated with HRAE or HF admissions. Conclusions: Advanced hemodynamic variables can serve as prognostic indicators for patients with LVADs. Low CPE and LVSWI are prognostic for higher mortality, but no variables were associated with HF admissions or HRAEs.

Early and Long-Term Outcomes of the Prophylactic Tricuspid Annuloplasty in Heart Transplantation

Abstract: Purpose Significant tricuspid regurgitation (TR) is considered to adversely affect the clinical outcomes of heart transplantation. Incidence of significant TR has been reported from 20% to 40%. Prophylactic donor heart tricuspid valve annuloplasty (TVA) has been routinely performed during heart transplantation in our institution. The purpose of this study is to summarize and evaluate early and long-term outcomes of prophylactic TVA in heart transplantation. Methods Between August 2011 and August 2021, 350 patients underwent heart transplantation, and 349 patients who underwent concomitant prophylactic TVA were included in this study. TVA was performed using the De Vega annuloplasty technique. TR grade was evaluated with echocardiography, and significant TR was defined as moderate or greater TR in at least two consecutive echocardiographic asssesment. We retrospectively reviewed clinical outcomes including pacemaker implantation, the incidence of significant TR and survival. Long-term survival was assessed between the cohorts who did and did not develop significant TR using the Kaplan-Meier method. Results The mean age was 52.9 ± 13.3 years old and 266 patients (76.2%) were male. Four patients (1.1%) required pacemaker implantation within 1 month after the transplantation: 2 patients for sinus node dysfunction, 1 patient for atrio-ventricular block, and 1 patient for left bundle branch block. Mean follow-up period was 43.8 ± 32.9 months. Ten patients (2.9%, 10/349) developed significant TR during the follow up period. The rate of freedom from significant TR was 98.2% at 1 year, 96.6% at 3 years and 96.6% at 5years. There was no occurrence of tricuspid valve stenosis. The 5-year survival rate of patients who developed significant TR was lower than those who did not (61.7% vs 83.9%, log rank=0.29). Conclusion Prophylactic TVA is safe during the heart transplantation with no TV stenosis and a low rate of patients requiring pacemaker implantation. The incidence of significant TR was exceptionally low compared to published reports. Development of postoperative significant TR might negatively affect the long-term survival compared to those who did not develop significant TR. Significant tricuspid regurgitation (TR) is considered to adversely affect the clinical outcomes of heart transplantation. Incidence of significant TR has been reported from 20% to 40%. Prophylactic donor heart tricuspid valve annuloplasty (TVA) has been routinely performed during heart transplantation in our institution. The purpose of this study is to summarize and evaluate early and long-term outcomes of prophylactic TVA in heart transplantation. Between August 2011 and August 2021, 350 patients underwent heart transplantation, and 349 patients who underwent concomitant prophylactic TVA were included in this study. TVA was performed using the De Vega annuloplasty technique. TR grade was evaluated with echocardiography, and significant TR was defined as moderate or greater TR in at least two consecutive echocardiographic asssesment. We retrospectively reviewed clinical outcomes including pacemaker implantation, the incidence of significant TR and survival. Long-term survival was assessed between the cohorts who did and did not develop significant TR using the Kaplan-Meier method. The mean age was 52.9 ± 13.3 years old and 266 patients (76.2%) were male. Four patients (1.1%) required pacemaker implantation within 1 month after the transplantation: 2 patients for sinus node dysfunction, 1 patient for atrio-ventricular block, and 1 patient for left bundle branch block. Mean follow-up period was 43.8 ± 32.9 months. Ten patients (2.9%, 10/349) developed significant TR during the follow up period. The rate of freedom from significant TR was 98.2% at 1 year, 96.6% at 3 years and 96.6% at 5years. There was no occurrence of tricuspid valve stenosis. The 5-year survival rate of patients who developed significant TR was lower than those who did not (61.7% vs 83.9%, log rank=0.29). Prophylactic TVA is safe during the heart transplantation with no TV stenosis and a low rate of patients requiring pacemaker implantation. The incidence of significant TR was exceptionally low compared to published reports. Development of postoperative significant TR might negatively affect the long-term survival compared to those who did not develop significant TR.

Accuracy of Estimated versus Calculated Mean Pulmonary Arterial Pressure

Abstract: Purpose Less than half of heart failure physicians calculate mean pulmonary arterial pressures (mPAP). Rather, they are reported from approximation between the systolic and diastolic pulmonary pressures. Imprecise assessment of mPAP will result in inaccurate calculation of the pulmonary vascular resistance (PVR), which can alter perceived eligibility for heart transplantation (HT). We sought to assess for differences between reported and calculated mPAP and associated PVR. Methods We retrospectively analyzed consecutive patients undergoing right heart catheterization with milrinone drug study at our institution (2/2013-11/2019). Hemodynamics were measured at baseline and again after a 50 mcg/kg milrinone load. We retrospectively calculated the mPAP as (2/3)*(diastolic PA) + (1/3)*(systolic PA), as well as the corresponding PVR. We compared the median reported and calculated mPAPs at baseline and following milrinone study. Finally, we assessed the number of patients in which calculation of mPAP reclassified the PVR across the cut-off of 3.5 WU, which is often used to determine eligibility for HT. Results A total of 224 patients were included - median age 57 (IQR 48-66) years, 34% women, and 31% ischemic cardiomyopathy. At baseline, median mPAP remained the same when comparing the calculated (40 mmHg, IQR 31-47) versus the reported mPAP (40 mmHg, IQR 32-48), though calculation resulted in significantly less variation in measurements (p<0.001). Calculated PVR, 3.5 WU (IQR 2.3-4.6), was significantly lower than reported PVR, 3.8 WU (IQR 2.5-5.1), p< 0.001. After milrinone study, final calculated mPAP, 33 mmHg (IQR 26-41), again had significantly less variability compared to reported, 33 mmHg (IQR 25-42), p<0.001, and subsequent PVR was significantly lower with calculated mPAP, PVR 2.65 WU (IQR 1.88-3.70), compared to reported mPAP, PVR 2.78 WU (IQR 1.93-3.78), p<0.001. There were 46 patients (21%) in which the PVR transitioned across the PVR cutoff of 3.5 WU after calculation of mPAP - 40 (18%) had PVR decrease to ≤ 3.5 from > 3.5, and 6 (3%) had PVR increase to > 3.5 from ≤ 3.5. Conclusion Calculation of mPAP resulted in less variation in measurement, affecting downstream calculation of PVR. More than one in five patients had PVR values transition across the cut-off of 3.5 WU following calculation of mPAP, which could alter subsequent eligibility for HT. Less than half of heart failure physicians calculate mean pulmonary arterial pressures (mPAP). Rather, they are reported from approximation between the systolic and diastolic pulmonary pressures. Imprecise assessment of mPAP will result in inaccurate calculation of the pulmonary vascular resistance (PVR), which can alter perceived eligibility for heart transplantation (HT). We sought to assess for differences between reported and calculated mPAP and associated PVR. We retrospectively analyzed consecutive patients undergoing right heart catheterization with milrinone drug study at our institution (2/2013-11/2019). Hemodynamics were measured at baseline and again after a 50 mcg/kg milrinone load. We retrospectively calculated the mPAP as (2/3)*(diastolic PA) + (1/3)*(systolic PA), as well as the corresponding PVR. We compared the median reported and calculated mPAPs at baseline and following milrinone study. Finally, we assessed the number of patients in which calculation of mPAP reclassified the PVR across the cut-off of 3.5 WU, which is often used to determine eligibility for HT. A total of 224 patients were included - median age 57 (IQR 48-66) years, 34% women, and 31% ischemic cardiomyopathy. At baseline, median mPAP remained the same when comparing the calculated (40 mmHg, IQR 31-47) versus the reported mPAP (40 mmHg, IQR 32-48), though calculation resulted in significantly less variation in measurements (p<0.001). Calculated PVR, 3.5 WU (IQR 2.3-4.6), was significantly lower than reported PVR, 3.8 WU (IQR 2.5-5.1), p< 0.001. After milrinone study, final calculated mPAP, 33 mmHg (IQR 26-41), again had significantly less variability compared to reported, 33 mmHg (IQR 25-42), p<0.001, and subsequent PVR was significantly lower with calculated mPAP, PVR 2.65 WU (IQR 1.88-3.70), compared to reported mPAP, PVR 2.78 WU (IQR 1.93-3.78), p<0.001. There were 46 patients (21%) in which the PVR transitioned across the PVR cutoff of 3.5 WU after calculation of mPAP - 40 (18%) had PVR decrease to ≤ 3.5 from > 3.5, and 6 (3%) had PVR increase to > 3.5 from ≤ 3.5. Calculation of mPAP resulted in less variation in measurement, affecting downstream calculation of PVR. More than one in five patients had PVR values transition across the cut-off of 3.5 WU following calculation of mPAP, which could alter subsequent eligibility for HT.

Prognostic Implications and Characteristics of Low dd-cfDNA Results in Heart Transplant Patients with Biopsy Proven Rejection

Abstract: Purpose Donor-derived cell-free DNA (dd-cfDNA) has emerged as an important noninvasive marker of heart transplant allograft injury. The characteristics and prognostic implications of low level dd-cfDNA in patients with histological evidence of acute rejection is not known. Although considered the gold standard, endomyocardial biopsy is limited to focal tissue sampling and is subject to interobserver variability in its interpretation. Methods Patients enrolled in the Surveillance HeartCare Outcomes Registry (SHORE) with biopsy proven acute cellular rejection (ACR) and antibody mediated rejection (AMR) who had low levels of dd-cfDNA (<0.15%) were evaluated. A targeted amplification, next generation-sequencing assay (AlloSure®; CareDx, Inc.) was used to detect dd-cfDNA. Results The SHORE registry had 2029 patients in total. Patients with ACR 1R were excluded. Only those patients who had a dd-cfDNA level within 30 days of biopsy (mean 2.7 days) were included. 61 patients (male 78%, median age 48 years) had low dd-cfDNA and endomyocardial biopsy evidence of ACR ≥2R and/or AMR ≥1R. Mean duration of the biopsy from the time of transplant was 196.31 days (IQR 88-257 days). ACR was seen in 36 patients (35=2R, 1=3R) and AMR was seen in 27 patients (21=pAMR 1(H+), 6=pAMR2). 2 patients had both ACR and AMR. The mean ejection fraction (EF) at the time of the rejection was mostly preserved (ACR 2R=EF 62.8±5.6%,ACR 3R=EF 47.5%, and AMR 1=EF 60.9±6%, AMR 2=EF 61±4.7%). 2 patients (3.3%) died 330±31days after the initial diagnosis of rejection. None of the patients developed graft dysfunction at one year follow up. One patient developed coronary artery vasculopathy and 7 patients developed de novo DSA. Conclusion Patients with low dd-cfDNA and biopsy-confirmed rejection typically had lower grades of rejection and maintained preserved left ventricular function on echocardiography. There was no immediate death after rejection or graft dysfunction. In this preliminary analysis, low dd-cfDNA despite biopsy evidence of rejection appears to have favorable prognosis. Discordance between light-based histology and molecular histology has shown better correlation with dd-cfDNA levels, and so consideration of dd-cfDNA in treatment and immunosuppression management requires ongoing evaluation. Donor-derived cell-free DNA (dd-cfDNA) has emerged as an important noninvasive marker of heart transplant allograft injury. The characteristics and prognostic implications of low level dd-cfDNA in patients with histological evidence of acute rejection is not known. Although considered the gold standard, endomyocardial biopsy is limited to focal tissue sampling and is subject to interobserver variability in its interpretation. Patients enrolled in the Surveillance HeartCare Outcomes Registry (SHORE) with biopsy proven acute cellular rejection (ACR) and antibody mediated rejection (AMR) who had low levels of dd-cfDNA (<0.15%) were evaluated. A targeted amplification, next generation-sequencing assay (AlloSure®; CareDx, Inc.) was used to detect dd-cfDNA. The SHORE registry had 2029 patients in total. Patients with ACR 1R were excluded. Only those patients who had a dd-cfDNA level within 30 days of biopsy (mean 2.7 days) were included. 61 patients (male 78%, median age 48 years) had low dd-cfDNA and endomyocardial biopsy evidence of ACR ≥2R and/or AMR ≥1R. Mean duration of the biopsy from the time of transplant was 196.31 days (IQR 88-257 days). ACR was seen in 36 patients (35=2R, 1=3R) and AMR was seen in 27 patients (21=pAMR 1(H+), 6=pAMR2). 2 patients had both ACR and AMR. The mean ejection fraction (EF) at the time of the rejection was mostly preserved (ACR 2R=EF 62.8±5.6%,ACR 3R=EF 47.5%, and AMR 1=EF 60.9±6%, AMR 2=EF 61±4.7%). 2 patients (3.3%) died 330±31days after the initial diagnosis of rejection. None of the patients developed graft dysfunction at one year follow up. One patient developed coronary artery vasculopathy and 7 patients developed de novo DSA. Patients with low dd-cfDNA and biopsy-confirmed rejection typically had lower grades of rejection and maintained preserved left ventricular function on echocardiography. There was no immediate death after rejection or graft dysfunction. In this preliminary analysis, low dd-cfDNA despite biopsy evidence of rejection appears to have favorable prognosis. Discordance between light-based histology and molecular histology has shown better correlation with dd-cfDNA levels, and so consideration of dd-cfDNA in treatment and immunosuppression management requires ongoing evaluation.

The Effect of Race on Heart Transplant Outcomes by Age

Abstract: Purpose The 2021 ISHLT adult heart transplantation (HT) report showed worse survival for 18-39 year-olds in North America following HT compared to the 40-59 and 60+ age groups. Conversely, survival in Europe was worse with increase in age. We aim to assess each age cohort within the United Network Organ Sharing (UNOS) database for differences in survival after heart transplantation stratified by race. Methods All HTs performed from January 2004 to September 2020 from the UNOS database were included. Patients were divided into three age groups: 18-39, 40-59, and 60+. Multivariable analyses compared survival in Black, Asian, or Hispanic categories to White patients, and then adjusted for education and work status at time of HT listing. Kaplan-Meier survival analyses stratified by race were completed for each of the three age groups. Results A total of 44,031 patients were included in this analysis. In comparison to White patients aged 18-39, Black (HR 1.59, 95%CI 1.41-1.80, p<0.01) and Other (HR 1.51, 95%CI 1.04-2.21, p=0.03) patients of the same age group had significantly worse survival, while Asian patients (HR 1.02, 95%CI 0.74-1.42, p=0.90) and Hispanic patients (HR 0.91, 95%CI 0.74-1.11, p=0.34) did not. In patients age 40-59, Black patients had worse survival than White patients (HR 1.18, 95%CI 1.03-1.34, p<0.02), while Asian (HR 0.81, 95%CI 0.55-1.20, p=0.30), Hispanic (HR 0.99, 95%CI 0.80-1.21, p=0.90), or Other (HR 1.11, 95%CI 0.67-1.86, p=0.68) patients did not. In the 60+ age cohort, there were no differences in survival when stratifying by race (Figure 1A-C). In the 18-39 age cohort, employment conferred decreased mortality (HR 0.78, 95%CI 0.63-0.95, p<0.02). Similarly, increased education was associated with reduced mortality (HR 0.15-0.24, p<0.05). Conclusion Black and Other patients had increased post-HT mortality compared to their White, age-matched counterparts. This difference was prominent in the youngest age cohort, but was mitigated with increased age. Further analysis is needed to determine key drivers of these differences. The 2021 ISHLT adult heart transplantation (HT) report showed worse survival for 18-39 year-olds in North America following HT compared to the 40-59 and 60+ age groups. Conversely, survival in Europe was worse with increase in age. We aim to assess each age cohort within the United Network Organ Sharing (UNOS) database for differences in survival after heart transplantation stratified by race. All HTs performed from January 2004 to September 2020 from the UNOS database were included. Patients were divided into three age groups: 18-39, 40-59, and 60+. Multivariable analyses compared survival in Black, Asian, or Hispanic categories to White patients, and then adjusted for education and work status at time of HT listing. Kaplan-Meier survival analyses stratified by race were completed for each of the three age groups. A total of 44,031 patients were included in this analysis. In comparison to White patients aged 18-39, Black (HR 1.59, 95%CI 1.41-1.80, p<0.01) and Other (HR 1.51, 95%CI 1.04-2.21, p=0.03) patients of the same age group had significantly worse survival, while Asian patients (HR 1.02, 95%CI 0.74-1.42, p=0.90) and Hispanic patients (HR 0.91, 95%CI 0.74-1.11, p=0.34) did not. In patients age 40-59, Black patients had worse survival than White patients (HR 1.18, 95%CI 1.03-1.34, p<0.02), while Asian (HR 0.81, 95%CI 0.55-1.20, p=0.30), Hispanic (HR 0.99, 95%CI 0.80-1.21, p=0.90), or Other (HR 1.11, 95%CI 0.67-1.86, p=0.68) patients did not. In the 60+ age cohort, there were no differences in survival when stratifying by race (Figure 1A-C). In the 18-39 age cohort, employment conferred decreased mortality (HR 0.78, 95%CI 0.63-0.95, p<0.02). Similarly, increased education was associated with reduced mortality (HR 0.15-0.24, p<0.05). Black and Other patients had increased post-HT mortality compared to their White, age-matched counterparts. This difference was prominent in the youngest age cohort, but was mitigated with increased age. Further analysis is needed to determine key drivers of these differences.

Panel-Reactive Antibody Associated with Acute Rejection Episodes After Heart Transplantation: An Analysis of the UNOS Database

Abstract: Purpose The presence of circulating alloantibodies can prolong transplant waiting times and may be associated with worse post-transplant outcomes. Recently, patients undergoing heart transplantation have been found to possess higher panel reactive antibody (PRA) levels, but the impact of this finding is uncertain. We aimed to determine the association between an elevated PRA and subsequent episodes of acute rejection. Methods Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed HTs performed from January 2004 to September 2020. Multi-organ transplants and re-transplants were excluded from analysis. Site-reported “Most recent PRA Class I” and “Most Recent PRA Class II” were used to assess PRA level, and the “Acute Rejection Episodes” variable was used to identify acute rejection, regardless of use of anti-rejection therapies. Detection methodology between centers could vary. Patients were stratified into three groups: 1) No-PRA (PRA% = 0), 2) Some-PRA (PRA% >0 and <50), and 3) High-PRA (PRA% >50). Rates of acute rejection were compared by log-rank test, with multivariate analysis adjusting for clinically relevant factors. Results A total of 41,537 patients were included in this study. Approximately 19% of patients experienced at least one acute rejection event. When stratifying based on Most Recent PRA Class I, the Some-PRA and High-PRA groups had significantly higher rates of acute rejection episodes, OR 1.22 (95% CI 1.12-1.33, p <0.001) and OR 1.79 (95% CI 1.55-2.06, p <0.001), respectively. Similar findings were obtained when using Most Recent PRA Class II, OR 1.31, (95% CI 1.19-1.45, p <0.001) and OR 1.71 (95% CI 1.47-1.99, p <0.001), respectively. When adjusting for sex and pre-operative blood transfusions, the results remained generally consistent - Class I: OR 3.9 (95% CI 1.04-17, p <0.05) and OR 3.2 (95% CI 0.13-37, p = 0.38), respectively; Class II: OR 3.79 (95% CI 0.94-17, p = 0.065) and OR 18.58 (95% CI 1.42-467, p <0.05), respectively. Conclusion Elevated PRA levels are associated with acute rejection episodes after HT, irrespective of patient sex and pre-operative blood transfusions. Further research should be conducted to verify our findings prospectively and account for possible confounders. The presence of circulating alloantibodies can prolong transplant waiting times and may be associated with worse post-transplant outcomes. Recently, patients undergoing heart transplantation have been found to possess higher panel reactive antibody (PRA) levels, but the impact of this finding is uncertain. We aimed to determine the association between an elevated PRA and subsequent episodes of acute rejection. Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed HTs performed from January 2004 to September 2020. Multi-organ transplants and re-transplants were excluded from analysis. Site-reported “Most recent PRA Class I” and “Most Recent PRA Class II” were used to assess PRA level, and the “Acute Rejection Episodes” variable was used to identify acute rejection, regardless of use of anti-rejection therapies. Detection methodology between centers could vary. Patients were stratified into three groups: 1) No-PRA (PRA% = 0), 2) Some-PRA (PRA% >0 and <50), and 3) High-PRA (PRA% >50). Rates of acute rejection were compared by log-rank test, with multivariate analysis adjusting for clinically relevant factors. A total of 41,537 patients were included in this study. Approximately 19% of patients experienced at least one acute rejection event. When stratifying based on Most Recent PRA Class I, the Some-PRA and High-PRA groups had significantly higher rates of acute rejection episodes, OR 1.22 (95% CI 1.12-1.33, p <0.001) and OR 1.79 (95% CI 1.55-2.06, p <0.001), respectively. Similar findings were obtained when using Most Recent PRA Class II, OR 1.31, (95% CI 1.19-1.45, p <0.001) and OR 1.71 (95% CI 1.47-1.99, p <0.001), respectively. When adjusting for sex and pre-operative blood transfusions, the results remained generally consistent - Class I: OR 3.9 (95% CI 1.04-17, p <0.05) and OR 3.2 (95% CI 0.13-37, p = 0.38), respectively; Class II: OR 3.79 (95% CI 0.94-17, p = 0.065) and OR 18.58 (95% CI 1.42-467, p <0.05), respectively. Elevated PRA levels are associated with acute rejection episodes after HT, irrespective of patient sex and pre-operative blood transfusions. Further research should be conducted to verify our findings prospectively and account for possible confounders.

Abstract 14516: Systolic Slope of the Outflow Cannula Predicts Heart Failure Readmission Risk in Patients With Heartmate 3 Left Ventricular Assist Device

Abstract: Introduction: Left ventricular assist devices (LVAD) may lead to left ventricular (LV) recovery in patients with heart failure with reduced ejection fraction (HFrEF) via LV offloading and subsequent positive remodeling. Current echocardiographic markers of LV recovery in LVAD patients are not well defined. The peak systolic slope, also known as systolic acceleration, of the outflow cannula has recently been shown to be a marker of underlying LV contractility and a tool to assess for LV recovery. We hypothesized that variations in the systolic slope would predict heart failure (HF) admissions. Methods: A total of 63 unique patients with LVAD at The University of Chicago Medical Center had HeartMate 3 (HM3) outflow tract Doppler signals obtained during routine transthoracic echocardiography (TTE) of suitable quality between 2015 and 2022. Systolic acceleration, systolic deceleration, diastolic acceleration, and the presence of flow reversal were measured. Mortality and HF admissions were recorded up to one year from the date of the TTE. Results: Increased systolic acceleration through the HM3 outflow cannula was associated with a decreased 1-year HF admission risk (352.8 [241.9, 515.8] cm/sec 2 vs 249.2 [164.0, 316.5] cm/sec 2 among readmitted patients, p = 0.03; Figure 1A). Systolic deceleration also predicted 1-year HF admission (-318.6 [-477.9, -244.0] cm/sec 2 vs -217.8 [-304.5, -188.8] cm/sec 2 among readmitted patients, p = 0.04; Figure 1B). Other variables, including the presence of flow reversal and diastolic acceleration, were not significantly associated with HF admission risk. Conclusions: Systolic acceleration, which reflects LV contractility, and systolic deceleration, which represents LV relaxation, are predictive of HF admission in patients with the HM3 LVAD.

Abstract 15817: Hemodynamics of the UNOS Heart Allocation System: Is it Time to Add Objectivity to an Subjective System?

Abstract: Introduction: In the current United States Organ Sharing heart transplant allocation system, hemodynamic criteria, systolic blood pressure (SBP), cardiac index (CI), and pulmonary capillary wedge pressure (PCWP), are utilized to justify certain listing statuses. Hypothesis: We sought to identify how currently utilized, and advanced, hemodynamics discriminated patients by listing status. Methods: Retrospective analysis of the Scientific Registry of Transplant Candidates including all adults listed for heart transplant since the updated listing criteria went live in October 2018 was completed. In addition to SBP, CI, and PCWP, the mean advanced hemodynamic metrics of aortic pulsatility index (API), cardiac power output (CPO), left ventricular stroke work index (LVSWI), right ventricular stroke work index (RVSWI), and pulmonary artery pulsatility index (PAPI), were calculated for each status. Results: Since October 2018, 9,418 patients were listed for heart transplant, and 8,636 had complete hemodynamic data at time of listing. Currently utilized hemodynamic metrics failed to discriminate lower acuity statuses (3 through 6 for PCWP and CI; 4 through 6 for SBP). For advanced hemodynamic metrics, mean API was lowest for Status 1 patients, and rose consistently with increasing status with a clear stepwise and statistically significant difference for sequential statuses (p < 0.001). CPO and LVSWI were unable to discriminate statuses 3-6. For right-sided hemodynamics, PAPI was unable to discriminate statuses 2 through 6, and there were no significant differences across any status for RVSWI. Conclusions: API is the only hemodynamic metric that is able to differentiate patients on the heart transplant waiting list across all active statuses by increasing in a stepwise fashion. Incorporation of API into future iterations of the UNOS heart allocation system may help better risk stratify patients and minimize waitlist mortality.

The Gut Microbiome and Tacrolimus Dosing in the Peri-Heart Transplant Period

Abstract:

Purpose

Recent evidence suggest that the gut microbiome may influence tacrolimus dosing requirements, potentially through direct metabolism. The impact of the gut microbiome on tacrolimus requirements among heart transplant (HT) recipients during medication initiation is unknown. We aimed to evaluate the effect of the gut microbiome on tacrolimus dosing requirements among HT recipients in the peri-HT period.

Methods

We conducted a prospective, observational cohort study of all single organ HT recipients at a single center from 2020-2021. Stool samples were collected within 2 weeks of HT and underwent shotgun metagenomic analysis. Measures of microbial diversity, composition, and metabolomics were correlated to the ratio of tacrolimus serum level (L) to the total 24-hour dose (D) at time of post-HT discharge. HT recipients were further divided into 2 groups: above-median L/D ratio (slow metabolizers) and below-median L/D ratio (fast metabolizers).

Results

Thirty-two patients were included in the study. Stool samples were collected a median of 8 days (IQR [5, 11]) post-HT. Median time to discharge was 18 days (IQR [12, 23]). Median L/D ratio was 0.86 (IQR [0.52, 1.13]) with 18 patients in the slow metabolizer group and 16 in the fast metabolizer group (median L/D 1.28 vs 0.61, p = 0.001). The fast metabolizer group was on a higher tacrolimus dose at discharge than the slow metabolizer group (19 vs 9 mg/day, p<0.001). Demographic factors and within sample microbial diversity, i.e. α-diversity, as measured by inverse Simpson index was similar between groups. The fast metabolizer group was found to have lower abundance of the phylum Bacteroidetes (19% vs 39%, p = 0.03) and higher abundance of Firmicutes (67% vs 47%, p = 0.04) (Fig. 1). Both groups had similar levels of the gut microbial metabolites, secondary bile acids and short chain fatty acids.

Conclusion

HT recipients have variable tacrolimus dosing requirements in the immediate post-HT period. Differences in the abundance of gut microbes in the peri-HT period may influence these needs.

Prevalence of Clinical Events Following High Donor Derived Cell Free DNA in the Absence of Rejection in Heart Transplant Recipients

Abstract: Purpose Donor-derived cell free DNA (dd-cfDNA) is a noninvasive biomarker used to assess graft injury following heart transplant (HTx). While the relationship between increased levels of dd-cfDNA and acute cellular rejection (ACR) and antibody mediated rejection (AMR) has been well studied, less is known about the frequency of other processes that damage the allograft following an elevated dd-cfDNA measurement. The goal of this analysis was to assess the prevalence of clinical events following a high dd-cfDNA measurement in the absence of rejection. Methods This retrospective study included 223 HTx recipients from the Donor-Derived Cell-Free DNA-Outcomes AlloMap Registry (D-OAR) with elevated dd-cfDNA (AlloSure®), defined as a level ≥0.20% that did not occur within 14 days of biopsy proven ACR (grade ≥2R) or AMR (pAMR≥1). Clinical events included the presence of donor specific antibodies (DSA), cardiac allograft vasculopathy (CAV; ISHLT grade ≥1), graft dysfunction [left ventricular ejection fraction (LVEF) ≤45% or a proportional decrease in LVEF ≥25% from the first D-OAR study visit], ACR, AMR and death. Clinical data were collected for 180 days following the first elevated dd-cfDNA. Allosensitization was defined as a pre-transplant panel reactive antibody ≥10%. Results The study consisted of 68% men and 71% Caucasians (mean ± SD age at HTx 52 ± 14 years), with non-ischemic cardiomyopathy (46%) representing the primary reason for HTx. The median time post-HTx to the first non-rejection elevated dd-cfDNA was 241 days (IQR 154-362). Fifty-seven of the 223 patients (26%), of whom 6 were allosensitized, experienced 70 clinical events in the 180 days post-elevated dd-cfDNA. The presence of at least one DSA (n=36) was the most common clinical event, of which 28/36 (78%) were de novo DSA. Graft dysfunction (n=14), CAV (n=9), AMR (n=5), death (n=4), and ACR (n=2) were the next most common. Median time (IQR) from elevated dd-cfDNA to these events was as follows: DSA, 37 days (15-104); graft dysfunction, 22 days (0-77); AMR, 70 days (42-91); and death, 100 days (75-124). Conclusion Elevated dd-cfDNA levels in the absence of allograft rejection appeared to precede the development of clinically relevant events within the next 6 months. Further studies are needed to determine whether elevated dd-cfDNA should trigger a change in clinical management. Donor-derived cell free DNA (dd-cfDNA) is a noninvasive biomarker used to assess graft injury following heart transplant (HTx). While the relationship between increased levels of dd-cfDNA and acute cellular rejection (ACR) and antibody mediated rejection (AMR) has been well studied, less is known about the frequency of other processes that damage the allograft following an elevated dd-cfDNA measurement. The goal of this analysis was to assess the prevalence of clinical events following a high dd-cfDNA measurement in the absence of rejection. This retrospective study included 223 HTx recipients from the Donor-Derived Cell-Free DNA-Outcomes AlloMap Registry (D-OAR) with elevated dd-cfDNA (AlloSure®), defined as a level ≥0.20% that did not occur within 14 days of biopsy proven ACR (grade ≥2R) or AMR (pAMR≥1). Clinical events included the presence of donor specific antibodies (DSA), cardiac allograft vasculopathy (CAV; ISHLT grade ≥1), graft dysfunction [left ventricular ejection fraction (LVEF) ≤45% or a proportional decrease in LVEF ≥25% from the first D-OAR study visit], ACR, AMR and death. Clinical data were collected for 180 days following the first elevated dd-cfDNA. Allosensitization was defined as a pre-transplant panel reactive antibody ≥10%. The study consisted of 68% men and 71% Caucasians (mean ± SD age at HTx 52 ± 14 years), with non-ischemic cardiomyopathy (46%) representing the primary reason for HTx. The median time post-HTx to the first non-rejection elevated dd-cfDNA was 241 days (IQR 154-362). Fifty-seven of the 223 patients (26%), of whom 6 were allosensitized, experienced 70 clinical events in the 180 days post-elevated dd-cfDNA. The presence of at least one DSA (n=36) was the most common clinical event, of which 28/36 (78%) were de novo DSA. Graft dysfunction (n=14), CAV (n=9), AMR (n=5), death (n=4), and ACR (n=2) were the next most common. Median time (IQR) from elevated dd-cfDNA to these events was as follows: DSA, 37 days (15-104); graft dysfunction, 22 days (0-77); AMR, 70 days (42-91); and death, 100 days (75-124). Elevated dd-cfDNA levels in the absence of allograft rejection appeared to precede the development of clinically relevant events within the next 6 months. Further studies are needed to determine whether elevated dd-cfDNA should trigger a change in clinical management.

Child‐Turcotte‐Pugh versus MELD‐XI identify distinct high‐risk populations for heart transplantation following ventricular assist device placement

Abstract: Patients with end‐stage heart failure frequently have significant congestive hepatopathy requiring hepatology assessment prior to heart transplantation listing. An elevated Model for End‐stage Liver Disease score with modification to exclude INR (MELD‐XI) has been associated with increased mortality following heart transplantation (HT). This study's primary aim was to examine whether Child‐Turcotte‐Pugh (CTP) classification is associated with post‐transplant mortality in patients bridged to transplant with left ventricular assist devices.

Racial and Gender Disparities in the Prognostic Value of Galectin-3 in Post Left Ventricular Assist Device Outcomes

Abstract: Purpose Galectin-3 is a novel biomarker, with elevated levels being linked to greater cardiovascular risk and poor outcomes in heart failure (HF) patients. McEvoy et al. found that Galectin-3 has better predictive value of HF outcomes in Caucasians compared to African Americans, however, this relationship and gender disparities have not been well explored in the Left Ventricular Assist Device (LVAD) population. The purpose of this study was to investigate gender and racial disparities in the LVAD population. Methods From 2012 to 2020, 171 LVAD patients at our institution had lab values collected for Galectin-3. Of these, 73 were African American, 76 were Caucasian, 110 were male, and 61 were female. Their outcomes, including right ventricular failure (RVF), time on inotropes, need for right ventricular assist device (RVAD), length ICU stay, and mortality were collected retrospectively. Results There was no significant difference in demographic variables besides age and BSA (Table 1). Galectin-3 correlated to inotrope duration in both African Americans (r=0.312, p=0.008) and Caucasians (r=0.295, p=0.013), but was only correlated with ICU stay in Caucasians (r=0.352, p=0.003), and not in African Americans (r=-0.006, p=0.963) There was significant correlation between Galectin-3 and Creatinine in Caucasians (r=0.425, p=0.001), but not in African Americans (r=0.078, p=0.509)Galectin-3 predicted inotrope duration in males (r=0.32, p=0.001) but not in females (r=0.28, p=0.07). Correlation was also found between Galectin-3 and Creatinine in males (r=-0.27, p=0.005), but not in females (r=-0.09, p=0.55). Galectin-3 predicted mortality in males with mean Galectin-3 of 28.6 ± 11.3 in those who died compared to 25.0 ± 12.2 in those who did not (p=0.05), while it did not in females, with mean Galectin-3 of 29.3 ± 17.6 in those who died compared to 28.0 ± 13.1 in those who did not (p=0.78). Conclusion The prognostic implications of Galectin-3 may be more pronounced in certain gender and racial groups. Galectin-3 is a novel biomarker, with elevated levels being linked to greater cardiovascular risk and poor outcomes in heart failure (HF) patients. McEvoy et al. found that Galectin-3 has better predictive value of HF outcomes in Caucasians compared to African Americans, however, this relationship and gender disparities have not been well explored in the Left Ventricular Assist Device (LVAD) population. The purpose of this study was to investigate gender and racial disparities in the LVAD population. From 2012 to 2020, 171 LVAD patients at our institution had lab values collected for Galectin-3. Of these, 73 were African American, 76 were Caucasian, 110 were male, and 61 were female. Their outcomes, including right ventricular failure (RVF), time on inotropes, need for right ventricular assist device (RVAD), length ICU stay, and mortality were collected retrospectively. There was no significant difference in demographic variables besides age and BSA (Table 1). Galectin-3 correlated to inotrope duration in both African Americans (r=0.312, p=0.008) and Caucasians (r=0.295, p=0.013), but was only correlated with ICU stay in Caucasians (r=0.352, p=0.003), and not in African Americans (r=-0.006, p=0.963) There was significant correlation between Galectin-3 and Creatinine in Caucasians (r=0.425, p=0.001), but not in African Americans (r=0.078, p=0.509)Galectin-3 predicted inotrope duration in males (r=0.32, p=0.001) but not in females (r=0.28, p=0.07). Correlation was also found between Galectin-3 and Creatinine in males (r=-0.27, p=0.005), but not in females (r=-0.09, p=0.55). Galectin-3 predicted mortality in males with mean Galectin-3 of 28.6 ± 11.3 in those who died compared to 25.0 ± 12.2 in those who did not (p=0.05), while it did not in females, with mean Galectin-3 of 29.3 ± 17.6 in those who died compared to 28.0 ± 13.1 in those who did not (p=0.78). The prognostic implications of Galectin-3 may be more pronounced in certain gender and racial groups.

Concomitant left atrial appendage closure during left ventricular assist device surgery can reduce ischaemic cerebrovascular accidents

Abstract: Abstract OBJECTIVES It remains unknown if the left atrial appendage closure (LAAC) at the time of left ventricular assist device (LVAD) surgery can reduce ischaemic cerebrovascular accidents. METHODS Consecutive 310 patients who underwent LVAD surgery with HeartMate II or 3 between January 2012 and November 2021 were included in this study. The cohort was divided into 2 groups: patients with LAAC (group A) and without LAAC (group B). We compared the clinical outcomes including the incidence of cerebrovascular accident between 2 groups. RESULTS Ninety-eight patients were included in group A, and 212 patients in group B. There were no significant differences between 2 groups in age, preoperative CHADS2 score and history of atrial fibrillation. In-hospital mortality did not differ significantly between the 2 groups (group A: 7.1%, group B: 12.3%, P = 0.16). Thirty-seven patients (11.9%) experienced ischaemic cerebrovascular accident (5 patients in group A and 32 patients in group B). The cumulative incidence from ischaemic cerebrovascular accidents in group A (5.3% at 12 months and 5.3% at 36 months) was significantly lower than that in group B (8.2% at 12 months and 16.8% at 36 months; P = 0.017). In a multivariable competing risk analysis, LAAC was associated with reducing ischaemic cerebrovascular accidents (hazard ratio 0.38, 95% confidence interval 0.15–0.97, P = 0.043). CONCLUSIONS Concomitant LAAC in LVAD surgery can reduce ischaemic cerebrovascular accidents without increasing perioperative mortality and complications.

Implications of Heart Rate in Patients with Left Ventricular Assist Devices.

Abstract: Optimal heart rate (HR) is a promising therapeutic target in patients with heart failure with reduced ejection fraction. Nevertheless, the implication of optimal HR in patients with left ventricular assist devices (LVAD) remains unknown. The cohort included consecutive patients with sinus rhythm undergoing LVAD implantation between 2014 and 2018. Ideal HR was calculated as follows: 93 - 0.13 × (deceleration time [msec]). The impact of "HR difference," defined as an HR difference between the actual HR at discharge and the calculated ideal HR, on the 1-year mortality and heart failure readmissions was investigated. A total of 143 patients (55 years old, 101 men) was identified and tertiled considering their HR differences: (1) the optimal HR group (n = 49; HR difference < 27 bpm), (2) the suboptimal HR group (n = 47; HR difference = 27-42 bpm), and (3) the nonoptimal HR group; HR difference (n = 47; HR difference > 43 bpm). The nonoptimal HR group had a significantly higher 1-year cumulative incidence of the primary endpoint compared with the optimal HR group (38% versus 16%, P = 0.029) with a hazard ratio of 1.69 (95% confidence interval 1.02-2.57) adjusted for 6 potential confounders. In conclusion, nonoptimized HR negatively affected clinical outcomes in LVAD patients. The implication of deceleration time-guided HR optimization in LVAD patients should be further investigated.

Postoperative tolvaptan use in left ventricular assist device patients: The TOLVAD randomized pilot study.

Abstract: PURPOSE Tolvaptan, a selective vasopressin type-2 antagonist, has been shown to increase serum sodium (Na) and urine output in hyponatremic left ventricular assist device (LVAD) patients in retrospective studies. In this prospective randomized pilot study, we aimed to assess the efficacy of tolvaptan in this population. METHODS We conducted a prospective, randomized, non-blinded pilot study of LVAD recipients with post-operative hyponatremia (Na < 135 mEq/L) (NCT05408104). Eligible participants were randomized to receive tolvaptan 15 mg daily in addition to usual care versus usual care alone. The primary outcome was a change in Na level and estimated glomerular filtration rate (eGFR), from the first post-operative day of hyponatremia (the day of randomization) to discharge. RESULTS A total of 33 participants were enrolled, and 28 underwent randomization (median age 55 [IQR 50-62]), 21% women, 54% Black, 32% ischemic cardiomyopathy, median baseline Na 135 (IQR 134-138). Fifteen participants were randomized to tolvaptan (TLV) and 13 were randomized to usual care alone (No-TLV). Mean change in Na from randomization to discharge in the TLV group was 2.7 mEq/L (95%CI 0.7-4.7, p = 0.013) and 1.8 (95%CI 0.5-4.0, p = 0.11) in the No-TLV group, though baseline and final Na levels were similar between groups. The mean change in eGFR was 2.6 ml/min/1.73 m2 (95%CI 10.1-15.3, p = 0.59) in TLV versus 7.5 ml/min/1.73 m2 (95%CI 5.2-20.2, p = 0.15) in No-TLV. TLV participants had significantly more urine output than No-TLV patients during their first 24 h after randomization (3294 vs 2155 ml, p = 0.043). CONCLUSION TLV significantly increases urine output, with nominal improvement in Na level, in hyponatremic post-operative LVAD patients without adversely impacting renal function.

Abstract 15000: Advanced Hemodynamics in the Assessment of Waitlist Mortality

Abstract: Introduction: Our analysis seeks to determine whether it or advanced hemodynamic variables, including aortic pulsatility index (API), pulmonary artery pulsatility index (PAPI), left ventricular stroke work index (LVSWI), or right ventricular stroke work index (RVSWI), correlated more strongly than traditional metrics with waitlist mortality for heart transplant. Hypothesis: Advanced hemodynamic markers of cardiac function, including API and PAPI, correlate more strongly with waitlist mortality than traditional hemodynamic criteria, including SBP and PCWP. Methods: This retrospective analysis of the Scientific Registry of Transplant Candidates (SRTR) included adults listed at all Statuses after the new heart allocation system in 2018. Hemodynamic data was obtained for patients listed after the 2018 policy change. Kaplan-Meier survival analysis was completed, with API, PAPI, LVSWI, and RVSWI as the independent variable stratified into quintiles. Results: There were 9,418 patients listed for heart transplant since the new policy implementation, with 8,636 patients with complete hemodynamic data at listing. Kaplan-Meier survival analysis revealed that API and LVSWI were best at stratifying patients appropriately in terms of waitlist survival with homogeneity of dispersion between groups (Figure 1), (lowest API quintile to highest: HR 2.04, 95%CI 1.94 - 2.15; HR 1.70, 1.59 - 1.81; HR 1.40, 1.29-1.51; HR 1.19, 1.08 - 1.30). The traditional parameters of PCWP, CO and systolic blood pressure had considerable dispersion of risk between quintiles while the right-sided parameters of PAPI and RVSWI did not. Conclusions: Advanced left-sided hemodynamic parameters better risk strategy waitlist mortality and the urgent need for heart transplantation than traditional metrics or right-sided advanced parameters.

Organ Care System Heart Perfusion Registry (OHP Registry) - Overview of a National Data Repository of Ex-Vivo Perfusion in DBD and DCD Heart Transplantation

Abstract: Purpose Organ Care System (OCS, Transmedics Inc) is the first clinically available system for ex-vivo normothermic heart perfusion. OHP Registry is a prospective real-world registry of Donation after Brain Death (DBD) or Donation after Circulatory Death (DCD) heart transplantation in hearts perfused and assessed on OCS Heart. OHP Registry will collect OCS ex-vivo perfusion & assessment parameters and post-transplant short & long-term clinical outcomes of heart transplant recipients in the U.S. Methods All adult heart transplant recipients of DBD or DCD heart allografts perfused and assessed on OCS Heart technology will be included, along with data on hearts perfused and assessed on OCS Heart but not transplanted. OCS Heart perfusion and assessment parameters will be prospectively collected. All recipients will be followed up to 5 years post-transplant. Patient and graft survival will be compared to a UNOS/SRTR cohort of heart transplant recipients of cold stored donor hearts transplanted at the same OHP Registry centers over the same period of time. Results Endpoints: Patient and graft survival at 1, 2, 3, 4, 5 years post-transplantation. Incidence of moderate or severe heart primary graft dysfunction (left or right ventricle) defined according to ISHLT 2014 consensus definitions. OCS Heart utilization rate defined as the number of hearts transplanted by OCS perfusion and assessment, divided by the total number of hearts perfused and assessed on the OCS Heart System. Conclusion We anticipate analyses of OHP Registry will provide important data that will inform clinical care. We plan to present regular updates at future ISHLT Annual Meetings. Organ Care System (OCS, Transmedics Inc) is the first clinically available system for ex-vivo normothermic heart perfusion. OHP Registry is a prospective real-world registry of Donation after Brain Death (DBD) or Donation after Circulatory Death (DCD) heart transplantation in hearts perfused and assessed on OCS Heart. OHP Registry will collect OCS ex-vivo perfusion & assessment parameters and post-transplant short & long-term clinical outcomes of heart transplant recipients in the U.S. All adult heart transplant recipients of DBD or DCD heart allografts perfused and assessed on OCS Heart technology will be included, along with data on hearts perfused and assessed on OCS Heart but not transplanted. OCS Heart perfusion and assessment parameters will be prospectively collected. All recipients will be followed up to 5 years post-transplant. Patient and graft survival will be compared to a UNOS/SRTR cohort of heart transplant recipients of cold stored donor hearts transplanted at the same OHP Registry centers over the same period of time. Endpoints: Patient and graft survival at 1, 2, 3, 4, 5 years post-transplantation. Incidence of moderate or severe heart primary graft dysfunction (left or right ventricle) defined according to ISHLT 2014 consensus definitions. OCS Heart utilization rate defined as the number of hearts transplanted by OCS perfusion and assessment, divided by the total number of hearts perfused and assessed on the OCS Heart System. We anticipate analyses of OHP Registry will provide important data that will inform clinical care. We plan to present regular updates at future ISHLT Annual Meetings.

Galectin-3 in Patients from 2012-2020: A Prognostic Biomarker of Left Ventricular Assist Device Post Implantation Outcomes

Abstract: Purpose Galectin-3 is a novel biomarker that has been used to risk stratify patients with heart failure. Elevated levels with values greater than 25.9 ng/mL are linked with poor outcomes and higher cardiovascular risk, however, outcomes in Left Ventricular Assist Device (LVAD) patients have not been well explored. We sought to investigate the relationship between Galectin-3 and outcomes in the LVAD population. Methods From 2012 to 2020, 249 patients with heart failure at our institution had lab values collected for Galectin-3. Among them, 171 patients underwent LVAD implantation. Lab and hemodynamic values, including Galectin-3, Creatinine, and PAPI, were collected for all patients prior to LVAD implant. Post-LVAD outcomes, including right ventricular failure (RVF), time on inotropes, need for right ventricular assist device (RVAD), length of ICU stay, and mortality were collected. Results There was no significant correlation between age, BMI, BSA and Galectin-3 (Table 1). Patients who experienced RVF (n=59) had a higher mean Galectin-3 compared to those who did not (n=112), with 30.9 ng/mL ± 15.21 compared to 24.9 ng/mL ± 10.7 (p=0.004). Those who received an RVAD (n=18) had higher Galectin-3 levels with mean 28.8 ng/mL ± 12.87 than those that did not (n=153) with mean 26.9 ng/mL ± 12.89 (p=0.558). Galectin-3 was positively correlated with inotrope duration (r=0.306, p=0.001), Creatinine (r=0.278, p=0.001) and length of ICU stay (r=0.191, p=0.022). Galectin-3 levels in patients who died (n=73) were higher than in those who did not (n=98), with a mean of 28.95 ng/mL ± 13.25 compared to 25.73 ng/mL ± 12.38 (p=0.11). Galectin-3 was negatively correlated to PAPI (r=-0.177, p=0.05), but was not significantly correlated to other hemodynamic parameters. Conclusion The Galectin-3 biomarker can be used as a predictor of post-LVAD implantation outcomes, elevated levels being associated with RVF, longer time on inotropes, increased length of ICU stay, decreased PAPI, and elevated creatinine. Galectin-3 is a novel biomarker that has been used to risk stratify patients with heart failure. Elevated levels with values greater than 25.9 ng/mL are linked with poor outcomes and higher cardiovascular risk, however, outcomes in Left Ventricular Assist Device (LVAD) patients have not been well explored. We sought to investigate the relationship between Galectin-3 and outcomes in the LVAD population. From 2012 to 2020, 249 patients with heart failure at our institution had lab values collected for Galectin-3. Among them, 171 patients underwent LVAD implantation. Lab and hemodynamic values, including Galectin-3, Creatinine, and PAPI, were collected for all patients prior to LVAD implant. Post-LVAD outcomes, including right ventricular failure (RVF), time on inotropes, need for right ventricular assist device (RVAD), length of ICU stay, and mortality were collected. There was no significant correlation between age, BMI, BSA and Galectin-3 (Table 1). Patients who experienced RVF (n=59) had a higher mean Galectin-3 compared to those who did not (n=112), with 30.9 ng/mL ± 15.21 compared to 24.9 ng/mL ± 10.7 (p=0.004). Those who received an RVAD (n=18) had higher Galectin-3 levels with mean 28.8 ng/mL ± 12.87 than those that did not (n=153) with mean 26.9 ng/mL ± 12.89 (p=0.558). Galectin-3 was positively correlated with inotrope duration (r=0.306, p=0.001), Creatinine (r=0.278, p=0.001) and length of ICU stay (r=0.191, p=0.022). Galectin-3 levels in patients who died (n=73) were higher than in those who did not (n=98), with a mean of 28.95 ng/mL ± 13.25 compared to 25.73 ng/mL ± 12.38 (p=0.11). Galectin-3 was negatively correlated to PAPI (r=-0.177, p=0.05), but was not significantly correlated to other hemodynamic parameters. The Galectin-3 biomarker can be used as a predictor of post-LVAD implantation outcomes, elevated levels being associated with RVF, longer time on inotropes, increased length of ICU stay, decreased PAPI, and elevated creatinine.