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Background: Since United Network for Organ Sharing (UNOS) revised their heart allocation policy in 2018, usage of veno-arterial extracorporeal life support (VA-ECLS) has dramatically increased as a bridge to transplant. This study investigated outcomes of VA-ECLS patients bridged to simultaneous heart-kidney transplant (SHK) in the new policy era., Methods: This study included 774 adult patients from the UNOS database who received SHK between 10/18/18 and 12/31/21 and compared patients bridged to transplant on VA-ECLS (n = 50) with those not bridged (n = 724)., Results: At baseline, SHK recipients bridged from VA-ECLS were younger (50.5 vs 58.0 years, p = 0.007), had higher estimated glomerular filtration rate (eGFR) at time of transplant (47.6 vs 30.1, p < 0.001), and spent fewer days on the waitlist (7.0 vs 33.5 days, p < 0.001). In the perioperative period, VA-ECLS was associated with higher rates of temporary dialysis (56.0% vs 28.0%, p < 0.001) but similar 2-year cumulative incidence of chronic dialysis (7.5% vs 5.4%, p = 0.800) and renal allograft failure (12.0% vs 8.1%, p = 0.500) compared to non-ECLS cohort. However, VA-ECLS patients had decreased survival to discharge (76.0% vs 92.7%, p < 0.001) and 2-year post-transplant survival (71.7% vs 83.0%, p = 0.004), as well as greater 2-year cumulative incidence of cardiac allograft failure (10.0% vs 2.7%, p = 0.002). Multivariable analyses found VA-ECLS at time of transplant to be independently associated with 2-year post-transplant mortality (HR [95% CI]: 3.40 [1.66-6.96], p = 0.001) and cardiac allograft failure (sub-distribution hazard ratio [SHR] [95% CI]: 8.51 [2.77-26.09], p < 0.001)., Conclusion: Under the new allocation policy, patients bridged to SHK from VA-ECLS displayed greater early mortality and cardiac allograft failure but similar renal outcomes compared to non-ECLS counterparts., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac hybrid positron emission tomography/computed tomography (PET/CT) has become a valid screening modality for cardiac allograft vasculopathy (CAV) following heart transplantation (HT). Visually estimated coronary artery calcium (VECAC) can be quantified from CT images obtained as part of PET/CT and has been shown to be associated with adverse cardiovascular outcomes in coronary artery disease. We investigated the prognostic value of VECAC following HT., Methods: A retrospective analysis of 430 consecutive adult HT patients who underwent 13 N-ammonia cardiac PET/CT from 2016 to 2019 with follow-up through October 15, 2022, was performed. VECAC categories included: VECAC 0, VECAC 1-9, VECAC 10-99, and VECAC 100+. The association between VECAC categories and outcomes was assessed using univariable and multivariable proportional hazards regression. The primary outcome was death/retransplantation., Results: The cohort was 73% male, 33% had diabetes, 67% had estimated glomerular filtration rate <60 ml/min, median age was 61 years, and median time since HT was 7.5 years. VECAC alone was insufficiently sensitive to screen for CAV. During a median follow-up of 4.2 years ninety patients experienced death or retransplantation. Compared with those with VECAC 0, patients VECAC 10-99 (HR 2.25, 95% CI 1.23-4.14, p = 0.009) and VECAC 100+ (HR 3.42, 95% CI 1.96-5.99, p < 0.001) experienced an increased risk of death/retransplantation. The association was similar for cardiovascular death and cardiovascular hospitalization. After adjusting for other predictors of death/retransplantation, VECAC 10-99 (VECAC 10-99: aHR 1.95, 95% CI 1.03-3.71 p = 0.04) and VECAC 100+ (VECAC 100+: aHR 2.33, 95% CI 1.17-4.63, p = 0.02) remained independently associated with death/retransplantation., Conclusions: VECAC is an independent prognostic marker of death/retransplantation following HT and merits inclusion as a part of post-HT surveillance PET/CT., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Hemocompatibility-related adverse events affect patients after left ventricular assist device (LVAD) implantation but are hard to predict., Objectives: Dynamic risk modeling with a multistate model can predict risk of gastrointestinal bleeding (GIB), stroke, or death in ambulatory patients., Methods: This was a secondary analysis of the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial. HeartMate 3 LVAD recipients who survived to hospital discharge and were followed for up to 2 years. A total of 145 variables were included in the multistate model with multivariate logistic regression. Model performance was assessed with the area under the curve in a holdout validation cohort. A risk stratification tool was created by dividing patients into categories of predicted risk using the final model variables and associated OR., Results: Among 2,056 LVAD patients, the median age was 59.4 years (20.4% women, 28.6% Black). At 2 years, the incidence of GIB, stroke, and death was 25.6%, 6.0%, and 12.3%, respectively. The multistate model included 39 total variables to predict risk of GIB (16 variables), stroke (10 variables), and death (19 variables). When ambulatory patients were classified according to their risk category, the 30-day observed event rate in the highest risk group for GIB, stroke, or death was 26.9%, 1.8%, and 4.8%, respectively. The multistate model predicted GIB, stroke, and death at any 30-day period with an area under the curve of 0.70, 0.69, and 0.86, respectively., Conclusions: The multistate model informs 30-day risk in ambulatory LVAD recipients and allows recalculation of risk as new patient-specific data become available. The model allows for accurate risk stratification that predicts impending adverse events and may guide clinical decision making. (MOMENTUM 3 IDE Clinical Study Protocol; NCT02224755)., Competing Interests: Funding Support and Author Disclosures Abbott is the sponsor of the MOMENTUM 3 studies. Abbott supported an investigator-initiated grant paid to the Inova Heart and Vascular Institute to support this effort; and Abbott has filed a U.S. provisional patent (U.S. Patent Application No. 63/421,450) for the work presented in the paper. Dr Shah is supported by National Institutes of Health K23 Career Development Award 1K23HL143179; has received consulting fees from Procyrion, Merck, and Natera; and grant support has been paid to his institution from Abbott, Roche, Merck, and Bayer. Dr Sayer has received consulting fees from Abbott. Dr Kanwar is on the medical advisory board for Abiomed, CorWave, and CareDx. Dr Cowger has served as a consultant for Abbott, Medtronic, Bioventrix, Endotronix, Bivacor, and Procyrion; and has received grant support and speaker fees from Abbott. Dr Pagani has served as an AD hoc scientific advisor without compensation for FineHeart, Medtronic, CH Biomedical, and Abbott; has served as medical monitor for Abiomed; is a member of the data safety monitoring board for Carmat and the National Heart, Lung, and Blood Institute PumpKIN clinical trial; and is Chair of the Society of Thoracic Surgeons Intermacs Task Force. Dr Mehra has received travel support and consulting fees, paid to Brigham and Women’s Hospital, from Abbott; has received fees for serving on a steering committee from Medtronic and Janssen (Johnson and Johnson); has received fees for serving on a data and safety monitoring board from Mesoblast; has received consulting fees from Natera, Paragonix, Moderna, Baim Institute of Clinical Research, and Broadview Ventures; and has received fees for serving as a scientific board member from NuPulseCV, Leviticus, and FineHeart. Dr Cleveland has received fees from Abbott and Medtronic. Dr Desai is on the speaker’s bureau for Abbott. Drs Lu, Hu, Connolly, and Kormos are employees of Abbott. Dr Uriel is a medical advisory board member for Livemetric, Levitcus, and Revamp; and receives grant support from Abbott, Abiomed, and Fire 1. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Interventricular interactions may be responsible for the decline in ventricular performance observed in various disease states that primarily affect the contralateral ventricle., Objectives: This study sought to quantify the impact of such interactions on right ventricular (RV) size and function using clinically stable individuals with left ventricular assist devices (LVADs) as a model for assessing RV hemodynamics while LV loading conditions were acutely manipulated by changing device speed during hemodynamic optimization studies (ie, ramp tests)., Methods: The investigators recorded RV pressure-volume loops with a conductance catheter at various speeds during ramp tests in 20 clinically stable HeartMate3 recipients., Results: With faster LVAD speeds and greater LV unloading, indexed RV end-diastolic volume increased (72.28 ± 15.07 mL at low speed vs 75.95 ± 16.90 at high speed; P = 0.04) whereas indexed end-systolic volumes remained neutral. This resulted in larger RV stroke volumes and shallower end-diastolic pressure-volume relationships. Concurrently, RV end-systolic pressure decreased (31.58 ± 9.75 mL at low speed vs 29.58 ± 9.41 mL at high speed; P = 0.02), but contractility, as measured by end-systolic elastance, did not change significantly. The reduction in RV end-systolic pressure was associated with a reduction in effective arterial elastance from 0.65 ± 0.43 mm Hg/mL at low speed to 0.54 ± 0.33 mm Hg/mL at high speed (P = 0.02)., Conclusions: Interventricular interactions resulted in improved RV compliance, diminished afterload, and did not reduce RV contractility. These data challenge the prevailing view that interventricular interactions compromise RV function, which has important implications for the understanding of RV-LV interactions in various disease states, including post-LVAD RV dysfunction., Competing Interests: Funding Support and Author Disclosures This project was supported, in part, by the American College of Cardiology and Merck Research Fellowship Award. Dr Brener has received consulting fees from Artract Medical and Osprey Medical. Dr Kanwar has served on the Medical Advisory Boards of Abiomed, CareDx, and CorWave. Dr Lander has served on the Medical Advisory Board of Abiomed. Dr Raina has received research support from United Therapeutics and Merck. Dr Sethi has received honoraria from Janssen and Chiessi; and has received institutional grant support from the American Heart Association’s COVID-19 Rapid Response Award. Dr Maurer has received funding from the National Institutes of Health (HL139671-01AL1 and AG K24AG036778); AD consulting income from Ionis, Alnylam, Eidos Therapeutics, Pfizer, Intellia, and Prothena; and his institution has also received funding for clinical trials for Ionis, Alnylam, Eidos Therapeutics, Pfizer, and Attralus. Dr Sayer has received consulting fees from Abbott. Dr Burkhoff has received an unrestricted institutional educational grant from Abiomed. Dr Uriel has received grant support from Abbott, Abiomed, and Fire1; and has served on the Medical Advisory Boards of Leviticus and Revamp. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Racial and ethnic disparities in provision of left ventricular assist device (LVAD) therapy have been identified. These disparities may be at least partially related to socioeconomic factors, including social support networks and financial constraints. This study aimed to identify specific barriers, and variations in institutional approaches, to the provision of equitable care to underserved populations. A survey was administered to 237 LVAD program personnel, including physicians, LVAD coordinators, and social workers, at more than 100 LVAD centers across 7 countries. Three fourths of respondents reported that their program required a support person to live with the LVAD patient for some period of time following implantation. In addition, 31% of respondents reported that patients with the inability to pay for medications are turned down at their program. The most significant barriers to successful LVAD implantation were lack of social support, lack of insurance, and lack of timely referral. The most consistently identified supports needed from the hospital system for success in underserved populations were the provision of a solution for patient transportation to and from hospital visits and the provision of financial support. This survey highlights the challenges facing LVAD programs that care for underserved patient populations and sets the stage for specific interventions aimed at reducing disparities in access to care., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is most commonly associated with obstructive symptoms and sudden cardiac death; however, predominantly nonobstructive advanced heart failure in HCM, marked by medically refractory disease with severe functional impairment, occurs in 5% to 7% of patients with HCM. The diagnosis relies on the integration of imaging (echocardiography/cardiac magnetic resonance), hemodynamic data, and cardiopulmonary exercise testing to identify the patients who will benefit from advanced heart failure therapies. Most advanced heart failure therapies focus on systolic dysfunction and are not always applicable to this patient population. Left ventricular assist devices may be an option in a highly selected population with left ventricular dilation. Heart transplantation is often the best option for patients with advanced heart failure in HCM with excellent post-transplantation survival., Competing Interests: Funding Support and Author Disclosures Dr Shimada was supported by the National Institutes of Health (R01 HL157216). Dr Maurer was supported by funding from the National Institutes of Health (HL139671-01, AG R21AG058348, and AG K24AG036778). Dr Clerkin was supported by the National Institutes of Health (K23 HL148528). Dr Shimada has received research support from the American Heart Association National Clinical and Population Research Awards, an American Heart Association Career Development Award, the Korea Institute of Oriental Medicine, a Columbia University Irving Medical Center Irving Institute for Clinical and Translational Research Precision Medicine Pilot Award, and Bristol Myers Squibb; and consulting income from Bristol Myers Squibb; and his institution has also received funding for clinical trials for Bristol Myers Squibb. Dr Maurer has received consulting income from Akcea, Alnylam, Eidos Therapeutics, Pfizer, Prothena, Novo Nordisk, and Intellia; and his institution has also received funding for clinical trials for Alnylam, Eidos Therapeutics, Pfizer, and Prothena. Dr Sayer has received consulting fees from Abbott. Dr Uriel has received grants from Abbott, Abiomed, and Fire 1; and served on the medical advisory board for Livemetric, Leviticus, and Revamp outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The 2018 heart allocation policy sought to improve risk stratification and reduce waitlist mortality for the sickest patients. This study sought to evaluate changes in wait times for the highest priority patients since policy implementation. All adult single-organ transplant recipients were identified in the United Network for Organ Sharing registry from October 18, 2018, to July 8, 2022, and separated into 4 periods. Outcomes were compared by blood type and UNOS region. Over the study period, 897 of 9,143 patients were listed as status 1 with no significant change in median wait time by blood type or region. More patients were listed as status 2 (4,523/9,143), and each subsequent period postpolicy change was associated with a 4.2-day increase in mean status 2 waitlist time (95% confidence interval 3.0-5.5, p < 0.0001). Wait times were longest for candidates with blood type O and shortest for AB & A. Regional variations continued, however, wait time increased in every region over time., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: In patients with the HeartMate 3 (HM3, Abbott) left ventricular (LV) assist device (LVAD), outflow graft narrowing has been reported as a result of accumulation of biodebris either internal or external to the graft. This study describes the prevalence, imaging findings, and clinical outcomes associated with HM3 LVAD outflow graft narrowing., Methods: A single-center retrospective cohort study was performed in patients who received an HM3 LVAD between November 2014 and July 2019. All patients with a computed tomographic (CT) angiogram or a CT scan with intravenous contrast sufficient to evaluate the outflow graft lumen were included. Narrowing was defined as a hypodensity of ≥3 mm., Results: Of 165 HM3 LVAD recipients, 46 (28%) had qualifying imaging. Outflow graft narrowing was present in 33% (15/46). One patient had complete obstruction requiring emergency surgery, whereas 14 patients had a median hypodensity of 4.5 mm (interquartile range, 3.3-5.8 mm). The presence of outflow graft narrowing was significantly associated with a longer duration of LVAD support (588.2 ± 277.5 days vs 131.5 ± 170.9 days; P < .0001). One-year survival after identification of narrowing was 93%, with death occurring in 1 patient with complete obstruction. LV unloading (mean percent decrease in LV end-diastolic diameter at time of CT imaging vs pre-LVAD) was 16.7% vs 17.7% in patients with and without narrowing, respectively (P = .86)., Conclusions: Among patients with adequate imaging, one-third have evidence of narrowing. Outflow graft narrowing secondary to biodebris was more likely to be found in HM3 LVAD recipients with longer duration of LVAD support. There was no significant difference in LV unloading between patients with and without narrowing., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Propionic acidemia (PA) is a rare inherited metabolic disease due to inborn errors of metabolism. PA results in the accumulation of abnormal organic acid metabolites in multiple systems, mainly the central nervous system and the heart. Cardiac complications include dilated cardiomyopathy (DCM) and carry a 40-50% increased mortality risk. Liver transplantation (LT) is required in PA patients when medical treatment fails and may prevent or slow down the cardiomyopathy progression. However, severe heart disease may be a serious contraindication to LT. We present a complicated case of a PA patient, supported with a Left Ventricular Assist Device, who underwent a heart and Liver transplant. PA patients are at increased risk for metabolic acidosis during surgery, with increased anion gap and hyperammonemia. A strict multi-disciplinary approach is needed to prevent and treat metabolic decompensation. The patient had a successful heart and liver transplant after a strict treatment protocol in the pre, intra, and post-operative periods. His case highlights the complexity of PA patients and the increased risk for metabolic decompensation during surgery and provides an insight into how to manage such complicated patients., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to discloses described by the American Journal of Transplantation., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: There are numerous risk-prediction models applied to acute myocardial infarction-related cardiogenic shock (AMI-CS) patients to determine a more accurate prognosis and to assist in patient triage. There is wide heterogeneity among the risk models including the nature of predictors evaluated and their specific outcome measures. The aim of this analysis was to evaluate the performance of 20 risk-prediction models in AMI-CS patients., Methods: Patients included in our analysis were admitted to a tertiary care cardiac intensive care unit with AMI-CS. Twenty risk-prediction models were computed utilizing vitals assessments, laboratory investigations, hemodynamic markers, and vasopressor, inotropic and mechanical circulatory support available from within the first 24 ​hours of presentation. Receiver operating characteristic curves were used to assess the prediction of 30-day mortality. Calibration was assessed with a Hosmer-Lemeshow test., Results: Seventy patients (median age 63 years, 67% male) were admitted between 2017 and 2021. The models' area under the curve (AUC) ranged from 0.49 to 0.79, with the Simplified Acute Physiology Score II score having the most optimal discrimination of 30-day mortality (AUC: 0.79, 95% confidence interval [CI]: 0.67-0.90), followed by the Acute Physiology and Chronic Health Evaluation-III score (AUC: 0.72, 95% CI: 0.59-0.84) and the Acute Physiology and Chronic Health Evaluation-II score (AUC: 0.67, 95% CI: 0.55-0.80). All 20 risk scores demonstrated adequate calibration ( p > 0.05 for all)., Conclusions: Among the models tested in a data set of patients admitted with AMI-CS, the Simplified Acute Physiology Score II risk score model demonstrated the highest prognostic accuracy. Further investigations are required to improve the discriminative capabilities of these models or to establish new, more streamlined and accurate methods for mortality prognostication in AMI-CS., (© 2022 The Author(s).)

Background: De novo aortic insufficiency (AI) is a common adverse event after continuous-flow left ventricular assist device (LVAD) placement and is associated with morbidity and mortality. This study aims to compare the development of de novo AI between HeartMate 3 (Abbott) and HeartMate II LVAD recipients., Methods: A retrospective review was conducted of clinical characteristics and serial echocardiograms (1 month, 6 months, and 1 year postimplantation) of HeartMate 3 patients implanted between November 2014 and March 2019 and of HeartMate II patients implanted between April 2004 and December 2015 at Columbia University Irving Medical Center. One hundred twenty-two patients were excluded from analysis for a history of aortic valve surgery, concomitant aortic valve surgery with LVAD implant, or more than trace preoperative AI left untreated. De novo AI was defined as development of more than mild AI after LVAD implant., Results: Included in the study were 121 HeartMate 3 patients and 270 HeartMate II patients. After accounting for competing risks of death and transplantation, there was no significant difference in the development of de novo AI by 1 year postimplantation between HeartMate II and HeartMate 3 patients (P = .68). There was no significant difference in severity of AI developed up to 1 year post-implantation between HeartMate II and HeartMate 3 patients., Conclusions: Development of de novo AI is comparable between HeartMate 3 and HeartMate II patients. There is no significant difference in severity of AI between HeartMate II and HeartMate 3 patients., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Anticoagulation therapy management during venoarterial extracorporeal membrane oxygenation (ECMO) is particularly difficult in postcardiotomy shock patients given a significant bleeding risk. We sought to determine the effect of anticoagulation treatment on bleeding and thrombosis risk for postcardiotomy shock patients on ECMO., Methods: We retrospectively reviewed patients who received ECMO for postcardiotomy shock from July 2007 through July 2019. Characteristics of patients who had bleeding and thrombosis were investigated, and risk factors were assessed by multilevel logistic regression., Results: Of the 152 patients who received ECMO for postcardiotomy shock, 33 (23%) had 40 thrombotic events and 64 (45%) had 86 bleeding events. Predictors of bleeding were intraoperative packed red blood cell transfusion (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.01 to 1.09), platelet transfusion (OR 1.10; 95% CI, 1.05 to 1.16), international normalized ratio (OR 1.18; 95% CI, 1.02 to 1.37), and activated partial thromboplastin time greater than 60 seconds (OR 2.32; 95% CI, 1.14 to 4.73). Predictors of thrombosis were anticoagulant use (OR 0.39; 95% CI, 0.19 to 0.79), surgical venting (OR 3.07; 95% CI, 1.29 to 7.31), hemoglobin (OR 1.38; 95% CI, 1.06 to 1.79), and central cannulation (OR 2.06; 95% CI, 1.03 to 4.11). The daily predicted probability of thrombosis was between 0.075 and 0.038 for patients who did not receive anticoagulation and decreased to between 0.030 and 0.013 for patients who received anticoagulation treatment at activated partial thromboplastin times between 25 and 80 seconds., Conclusions: Anticoagulation therapy can reduce thromboembolic events in postcardiotomy shock patients on ECMO, but bleeding risk may outweigh this benefit at activated partial thromboplastin times greater than 60 seconds., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: This analysis sought to investigate the waitlist and post-transplant outcomes of individuals bridged to transplantation by using temporary percutaneous endovascular mechanical circulatory support (tMCS) through a status 2 designation (cardiogenic shock and exception)., Background: The 2018 donor heart allocation policy change granted a status 2 designation to patients supported with tMCS., Methods: Adult patients in the United Network for Organ Sharing registry after October 18, 2018 who received a status 2 designation for tMCS were included and grouped by their status 2 criteria: cardiogenic shock with hemodynamic criteria (CS-HD), cardiogenic shock without hemodynamic criteria before tMCS (CS-woHD), and exception. Baseline characteristics, waitlist events (death and delisting), and post-transplant outcomes were compared., Results: A total of 2,279 patients met inclusion criteria: 68.6% (n = 1,564) with CS-HD, 3.2% (n = 73) with CS-woHD, and 28.2% (n = 642) with exceptions. A total of 64.2% of patients underwent heart transplantation within 14 days of status 2 listing or upgrade, and 1.9% died or were delisted for worsening clinical condition. Among the 35.8% who did not undergo transplantation following 14 days, only 2.8% went on to receive a left ventricular assist device (LVAD). The 30-day transplantation likelihood was similar among groups: 80.1% for the CS-HD group vs 79.7% for the exception group vs 73.3% for the CS-woHD group; P = 0.31. However, patients who met criteria for CS-woHD had 2.3-fold greater risk of death or delisting (95% CI: 1.10-4.75; P = 0.03) compared with CS-HD patients after multivariable adjustment. Pre-tMCS hemodynamics were not associated with adverse waitlist events., Conclusions: The use of tMCS is an efficient, safe, and effective strategy as a bridge to transplantation; however, patients with CS-woHD may represent a high-risk cohort. Transition to a durable LVAD was a rare event in this group., Competing Interests: Funding Support and Author Disclosures Dr Clerkin is supported by National Heart, Lung and Blood Institute grant K23 HL148528. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The number of patients with adult congenital heart disease (ACHD) who require orthotopic heart transplantation has increased rapidly in the past 2 decades. This study examined heart transplant outcomes of patients with ACHD who had previous cardiac surgery by using data from the United Network for Organ Sharing database., Methods: Between January 2008 and March 2019, patients with ACHD who underwent previous cardiac surgery and subsequent heart transplantation were identified from the United Network for Organ Sharing database. As a control group, adult patients without congenital heart disease who had previous sternotomy and subsequent heart transplantation were extracted from the database. Propensity score matching was then used to compare outcomes between the 2 groups., Results: There were 793 patients in the ACHD group and 8400 patients in the control group. Among well-matched groups of 486 patients each, 30-day mortality (8.2% vs 3.9%; P = .004) and perioperative need for dialysis (22.7% vs 13.3%; P < .001) were significantly higher in the ACHD group compared with the control group. However, there was no difference in 10-year survival between the groups (ACHD 66.0% vs control 64.1%; log-rank P = .353)., Conclusions: Compared with well-matched patients without ACHD but with previous sternotomy, patients with ACHD and previous intracardiac repair had a higher operative risk but similar 10-year survival., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

HLA antibodies pose a significant barrier to transplantation and current strategies to reduce allosensitization are limited. We hypothesized that augmenting proteasome inhibitor (PI) based desensitization with costimulation blockade (belatacept) to mitigate germinal center (GC) responses might increase efficacy and prevent rebound. Four highly sensitized (calculated panel reactive antibody [cPRA] class I and/or II >99%, complement-dependent cytotoxicity panel reactive antibody [CDC PRA+], C1q+) heart transplant candidates were treated with the combination of belatacept and PI therapy, which significantly reduced both class I and II HLA antibodies and increased the likelihood of identifying an acceptable donor. Three negative CDC crossmatches were achieved against 3, 6, and 8 donor-specific antibodies (DSA), including those that were historically C1q+ binding. Posttransplant, sustained suppression of 3 of 3, 4 of 6, and 8 of 8 DSA (cases 1-3) was achieved. Analysis of peripheral blood mononuclear cells before and after desensitization in one case revealed a decrease in naïve and memory B cells and a reduction in T follicular helper cells with a phenotype suggesting recent GC activity (CD38, PD1, and ICOS). Furthermore, a shift in the natural killer cell phenotype was observed with features suggestive of activation. Our findings support synergism between PI based desensitization and belatacept facilitating transplantation with a negative CDC crossmatch against historically strong, C1q binding antibodies., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Tricuspid regurgitation (TR) is common in advanced heart failure (HF) patients. However, the effect of concomitant tricuspid valve repair or replacement (tricuspid valve intervention [TVI]) with left ventricular assist device (LVAD) implantation is controversial. The aim of this study was to investigate the longitudinal trend of TR after LVAD implantation and the effect of TVI on the TR trend and clinical outcomes., Methods: We retrospectively reviewed patients at our institution who underwent LVAD implantation between April 2014 and August 2018. We evaluated the grade of TR by echocardiography before and after LVAD implantation. Moderate or greater TR was defined as significant., Results: Among 199 consecutive patients, 194 had at least 2 echocardiographic TR assessments before and after LVAD implantation. Of these patients, 108 were included in the TVI-positive (TVI+) group and 86 in the TVI-negative (TVI-) group. In the TVI+ group, the prevalence of significant TR decreased from 52% to about 20% in the first 6 months after implantation (P < .01). Overall survival and HF readmission-free survival were comparable between the TVI+ and TVI- patients. In contrast, patients in both groups who had significant postoperative TR during early follow-up had worse 2-year HF readmission-free survival (36% in patients with significant postoperative TR vs 55% in those without significant postoperative TR; P = .028)., Conclusions: Concomitant TVI with LVAD implantation improved TR in most patients but did not have an impact on clinical outcomes. Significant postoperative TR after LVAD implantation, in patients with and without TVI, was associated with worse HF-free outcomes., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: HeartWare ventricular assist device (HVAD) cannula position is associated with hemodynamics and heart failure readmissions. However, its impact on hemocompatibility-related adverse events (HRAEs) remains uncertain., Methods: HVAD patients were followed for 1 year after index hospitalization, when cannula coronal angle was quantified from chest x-ray film. Invasive right heart catheterization and transthoracic echocardiography were performed. One-year occurrences of each HRAE were compared between those with and without a cannula coronal angle of greater than 65 degrees., Results: Among 63 HVAD patients (median age 60 years, 63% male), 10 (16%) had a cannula coronal angle greater than 65 degrees. The wide-angle group had elevated intracardiac pressures and lower pulmonary artery pulsatility index (P < .05). They also had reduced right ventricular function by echocardiography. Freedom from HRAEs tended to be lower in the wide-angle group (24% vs 62%; P = .11). The rate of gastrointestinal bleeding was significantly higher in the greater than 65 degrees group (0.90 events/year vs 0.40 events/year; P = .013). The rates of stroke and pump thrombosis were statistically comparable irrespective of cannula angle (P > .05)., Conclusions: HVAD cannula coronal angle was associated with reduced right ventricular function and HRAEs. Prospective studies evaluating surgical techniques to ensure optimal device positioning and its effects on HRAEs are warranted., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Aortic insufficiency (AI) significantly affects morbidity and mortality in patients with left ventricular assist devices. Although AI may be commonly assessed by echocardiography, expert techniques are required for accurate quantification of AI severity., Description: In this prospective blinded study, screenshots from the HVAD (Medtronic, Framingham, MA) display and simultaneous echocardiographic measurements were obtained. Each screenshot was digitized and the early diastolic phase slope was calculated, with blinding to the echocardiographic results. The regurgitant fraction of AI was quantified by Doppler echocardiography of the outflow graft., Evaluation: A total of 30 patients (median, 57 years old; 57% male) were enrolled. A cutoff of -17.6 L/min/s for the early diastolic phase slope had a sensitivity of 0.92 and a specificity of 0.53 to estimate significant AI with a regurgitant fraction of 30% or greater, and it significantly stratified patients into a low regurgitant faction group (0.3%) and a high regurgitant fraction group (33.0%) (P = .009). The early diastolic phase slope had a moderate correlation with the actually measured regurgitant fraction (r = .50)., Conclusions: The early diastolic phase slope of the HVAD flow waveform may be a parameter that can estimate the presence of clinically significant AI., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The acute angle between inflow cannula and device body of HeartMate II left ventricular assist device (LVAD) (Abbott, Pleasanton, California) is associated with device thrombosis. However, most studies utilized two-dimensional (2D) angle obtained from chest roentgenogram (CXR), which is unlikely accurate. We aimed to create and validate a formula to estimate actual three-dimensional (3D) angle., Methods: We retrospectively reviewed the cohort undergoing HeartMate II LVAD implantation between 2008 and 2016. A formula for calculating 3D angles of the LVAD inflow cannula relative to the device body was mathematically derived, using simple 2D measurements from CXR., Results: The cohort included consecutive 275 patients with HeartMate II (median age: 60 [25% quartile: 51, 75% quartile: 68] years). There was no significant difference between the calculated 3D angles (from formula) and actual 3D angles (from computed tomography) from the subset group with 3D computed tomography (n = 28) (71.7° ± 13.4° vs 71.1° ± 11.5°, P = .858). Among all participants, the calculated 3D angle (from formula) was 74.4° ± 14.2°, which was significantly larger than the 2D projected angle (from CXR) (65.2° ± 11.3°, P < .001). There was no statistical difference in the calculated 3D angles (from formula) between patients with/without device thrombosis, hemorrhagic stroke, ischemic stroke, or mortality (P > .05 for all)., Conclusions: We established a novel formula to mathematically calculate actual 3D angles between inflow cannula and device body of HeartMate II. The formula would help investigators to validate their findings of the relationship between 2D projected angle (from CXR) and device thrombosis., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The heart transplant (HT) guidelines recommendation to match recipient and donors within 30% of body weight lacks a strong evidence base and is not well established in patients bridged to transplant with left ventricular assist devices (LVAD). In light of the scarcity of donor hearts, we investigated the effect of size mismatch on hemodynamics, one-year survival and length of stay (LOS) following HT., Methods: Single-center retrospective analysis of consecutive HT patients from April 2007 to September 2017. Recipients were divided into 3 cohorts based on donor-to-recipient weight ratio (DRWR): (1) undersized (<0.7), (2) size-matched, (0.7-1.3); (3) oversized (>1.3)., Results: 288 consecutive patients were identified (mean age 53 ± 11 years; 76% male), 46 were undersized (0.61 ± 0.05), 210 size-matched (0.94 ± 0.16), and 32 oversized (1.65 ± 0.38). There was no significant difference in donor left ventricular end diastolic diameter (LVEDD) between the 3 groups (p = 0.11). The donor/recipient (D/R) predicted heart mass (PHM) was lowest in the undersized group (0.92 ± 0.13). There were no significant differences in 1-year survival in the overall and LVAD cohort (p = 0.65 and 0.59, respectively). Neither donor LVEDD nor D/R PHM differed among survivors or non-survivors. LOS was longer in the undersized group than the size-matched cohort (p = 0.004). The undersized group had hearts with the highest filling pressures and lowest cardiac index at 1 week among the remaining groups (p = 0.009, 0.017, and p = 0.05, respectively). There were no clinically significant differences in hemodynamics at 1 or 6 months., Conclusions: HT undersizing affects hemodynamics early but not later in the course and does not impact 1-year survival. The liberalization of size matching may increase the HT donor pool significantly., (Copyright © 2019. Published by Elsevier Inc.)

Background: This retrospective single-institutional study investigated the effect of significant valvular regurgitation after left ventricular assist device (LVAD) implantation and the role of concomitant valve surgery during LVAD surgery., Methods: All patients receiving an LVAD (HeartMate II; Abbott, Abbott Park, IL) during 2008 and 2015 were enrolled. The cohort was divided into two groups based on the valve status at the end of the operation: patients without significant valvular regurgitation (no-VR) and those with significant valvular regurgitation (residual-VR)., Results: An LVAD was implanted in 270 patients. Of these, 233 had significant preoperative valve disease(s), and 180 (66.6%) received concomitant valve interventions (35 aortic, 90 mitral, 138 tricuspid). At the completion of the LVAD operation, 204 had no-VR and 66 had residual-VR. Short-term outcomes were similar in two groups, except for longer cardiopulmonary bypass time in the no-VR group (149 minutes) than in the residual-VR group (132 minutes, p = 0.038). During follow-up, mean pulmonary artery pressure (24 mm Hg in no-VR vs 27 mm Hg in residual-VR; p = 0.018) and pulmonary vascular resistance (1.8 Wood units in no-VR vs 2.7 Wood units in residual-VR, p = 0.008) significantly improved in no-VR group compared with the residual-VR group. Survival and heart failure admission-free rates at 1 year were significantly superior in the no-VR group compared with the residual-VR group (1-year survival: 72% ± 3% No-VR vs 55% ± 6% residual-VR; log-rank p = 0.026; admission-free survival: 91% ± 2% no-VR vs 74% ± 7% residual-VR; log-rank p = 0.026). Concomitant valve intervention was not an independent predictor of in-hospital death and morbidity., Conclusions: Absence of valvular lesion after LVAD implantation was associated with improved midterm hemodynamics and survival in the current study. Aggressive surgical intervention for significant valve disease(s) at the time of LVAD implant may be beneficial to selected patients., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Neutropenia is a significant adverse event after heart transplantation (HT) and increases infection risk. Granulocyte colony-stimulating factor (G-CSF) is commonly used in patients with neutropenia. In this work, we assessed the adverse effects of G-CSF treatment in the setting of a university hospital., Methods: Data on HT patients from January 2008 to July 2016 were reviewed. Patients who received G-CSF were identified and compared with patients without a history of therapy. Baseline characteristics, rejection episodes, and outcomes were collected. Data were analyzed by incidence rates, time to rejection and survival were analyzed using Kaplan-Meier curves, and odds ratios were generated using logistic regression analysis., Results: Two hundred twenty-two HT patients were studied and 40 (18%) received G-CSF for a total of 85 total neutropenic events (0.79 event/patient year). There were no differences in baseline characteristics between the groups. In the 3 months after G-CSF, the incidence rate of rejection was 0.067 event/month. In all other time periods considered free of G-CSF effect, the incidence rate was 0.011 event/month. This rate was similar to the overall incidence rate in the non-GCSF group, which was 0.010 event/month. There was a significant difference between the incidence rates in the G-CSF group at 0 to 3 months after G-CSF administration and the non-GCSF group (p = 0.04), but not for the other time periods (p = 0.5). Freedom from rejection in the 3 months after G-CSF administration was 87.5% compared with 97.5% in the non-GCSF group (p = 0.006)., Conclusions: G-CSF administration was found to be associated with significant short-term risk of rejection. This suggests the need for increased surveillance during this time period., (Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Left ventricular assist devices (LVAD) provide a durable option for patients with advanced hear failure. Axial and centrifugal pump physiology differs with regard to the relationship between pump inflow-outflow cannula pressure differential and flow, which results in device behavior that can vary drastically under different loading conditions. Ramp studies can aid the clinician in choosing the optimal speed to adequately unload the left ventricle. Advances in 3-dimensional echocardiography enhance the understanding of chamber geometry for both types of LVADs. Novel outflow graft imaging techniques have been developed to better characterize aortic insufficiency, which may be underestimated with current standard methods., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Left ventricular assist devices (LVADs) significantly improve outcomes of advanced heart failure patients. However, patients continue to have high readmission rates due to complications ranging from bleeding, thrombosis, heart failure, and infection. Considering that the hallmark benefit of LVAD therapy is improvement in hemodynamics (cardiac unloading and increased cardiac output), hemodynamic assessment on LVAD support is key to better understand these difficult complications and may serve as a tool to resolving them. In this review, we will discuss the hemodynamic changes following LVAD implantation, and the implications and prognostic impact of hemodynamic optimization on outcomes and complications., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objectives: The purpose of this study was to investigate the differential impact of the 2 most commonly available left ventricular assist device (LVAD) types on the right ventricle (RV) and left ventricle (LV) using 3-dimensional (3D) echocardiography-based analysis of ventricular morphology., Background: LVADs have emerged as common therapy for advanced heart failure. Recent data suggest that the heart responds differently to speed settings in the 2 main devices available (HeartMate II [HMII], St Jude Medical, Pleasanton, California, and HVAD, HeartWare International, Framingham, Massachusetts). The authors hypothesized that 3D echocardiographic assessment of LV and RV volumes and shape would help describe the differential impact of the 2 LVAD types on the heart., Methods: Simultaneous 3D echocardiography, ramp test, and right heart catheterization were performed in 31 patients with LVADs (19 with HMII and 12 with HVAD). Device speed was increased stepwise (8,000 to 12,000 for HMII and 2,300 to 3,200 revolutions per minute for HVAD). 3D echocardiographic full-volume LV and RV datasets were acquired, and endocardial surfaces were analyzed using custom software to calculate LV sphericity, conicity (perfect sphere/cone = 1) and RV septal and free-wall curvature (0 = flat; <0 = concave; >0 = convex)., Results: For both devices, cardiac output increased and wedge pressure decreased with increasing speed. In HMII, LV volumes progressively decreased (meanΔ = 127 ml) as the LV became less spherical and more conical, whereas the RV volume initially remained stable, but subsequently increased at higher speeds (meanΔ = 60 ml). Findings for the HVAD were similar, but less pronounced (LV:meanΔ = 51 ml, RV:meanΔ = 22 ml), and the LV remained significantly more spherical even at high speeds. On average, in HMII patients, the RV septum became more convex (bulging into the LV) at the highest speeds whereas in HVAD patients, there was no discernable change in the RV septum., Conclusions: The heart responds differently to pump speed changes with the 2 types of LVAD, as reflected by the volume and shape changes of both the LV and RV. Our study suggests that adding RV assessment to the clinical echo-ramp study may better optimize LVAD speed. Further study is needed to determine whether this would have an impact on patient outcomes., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The intravascular ventricular assist system (iVAS) is a new, minimally invasive, ambulatory counterpulsation heart assist system delivered via the subclavian artery and powered by a portable driver. It is designed for recovery, bridge to transplantation (BTT) or for prolonging medical therapy. We report the first-in-human (FIH) experience with iVAS., Methods: This is a prospective, non-randomized single arm, U.S. Food and Drug Administration (FDA)-approved early feasibility trial in patients listed for cardiac transplantation. The primary end-point was survival to transplant or stroke-free survival at 30 days., Results: Fourteen patients were enrolled and 13 (92.8%) were treated with iVAS. At time of implant, the average age was 58 ± 6.7 years; 85% were male; 28% had ischemic cardiomyopathy; and 3 were Interagency Registry for Mechanically Assisted Devices (INTERMACS) Level 2, 9 were Level 3, and 1 was Level 4. The mean left ventricular ejection fraction was 22%, left ventricular internal diameter diastole was 7.13 mm, and 69% had moderate or severe mitral regurgitation. There were no intra-operative complications. Intensive care unit stay after implant was 6 ± 6 days. All patients were transplanted after 32 ± 21 days. There were no deaths or thromboembolic events: 1 patient required escalation of mechanical support, and post-implant complications included pleuritis/pericarditis (n = 1) and neuropathy (n = 2). No intra-operative blood transfusions were required., Conclusions: This study demonstrates a high rate of successful outcomes with an excellent risk-to-benefit profile. This FIH experience reveals that the iVAS can be successfully inserted in a standardized approach, provide hemodynamic support, can be interrupted for short periods, and allows for ambulation. A multicenter trial to investigate effectiveness and safety is warranted., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Indications for concomitant intervention for mitral regurgitation (MR) during left ventricular assist device (LVAD) implantation remain controversial. The objective of this study was to determine the impact of the surgical correction of MR during LVAD implantation., Methods: From July 2008 to December 2014, 164 patients with significant preoperative MR underwent LVAD (HeartMate II; Thoratec, Pleasanton, CA) implantation. The MR resolved after LVAD implantation in 110 of 164 patients (67.1%) with either surgical or spontaneous correction. The cohort (n = 110) without significant postoperative MR was divided into two groups: a spontaneous correction group (n = 54, MR spontaneously resolved after LVAD implantation); and a surgical correction group (n = 56, MR surgically corrected). Patients who received aortic valve procedures (n = 17) were excluded from this study., Results: Patient demographics, perioperative outcomes including bleeding, prolonged intubation, and stroke, and inhospital mortality did not differ in the two groups except for significantly longer cardiopulmonary bypass time in the surgical correction group (spontaneous correction 123 minutes [interquartile range (IQR): 107 to 150] versus surgical correction 177 minutes [IQR: 132 to 198], p < 0.001). During follow-up, pulmonary wedge pressure (spontaneous correction 17 mm Hg [IQR: 12 to 23 mm Hg] versus surgical correction 12 mm Hg [IQR: 4 to 17 mm Hg], p = 0.015) and pulmonary vascular resistance (spontaneous correction 2.0 Wood units [IQR: 1.5 to 2.4] versus surgical correction 1.7 Wood units [IQR: 0.8 to 2.1], p = 0.047) were significantly improved in the surgical correction group compared with the spontaneous correction group. Overall survival rate and freedom from recurrent MR were significantly better in the surgical correction group compared with the spontaneous correction group (1-year survival, spontaneous correction 59.4% ± 6.9% versus surgical correction 69.6% ± 6.4%, log rank p = 0.030; 1-year freedom from recurrent MR, spontaneous correction 76.2% ± 7.5% versus surgical correction 95.0% ± 3.5%, log rank p = 0.028)., Conclusions: The LVAD patients with surgically corrected MR had improved midterm hemodynamics and survival compared with spontaneously resolved MR, along with low recurrence of MR. Aggressive surgical mitral valve intervention during LVAD implantation may be recommended., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to evaluate the prognostic performance of novel echocardiographic (transthoracic echocardiography, or TTE) parameters for grading aortic insufficiency (AI) severity in patients with continuous-flow left ventricular assist devices (CF-LVADs). The development of AI after CF-LVAD implantation is common, although the clinical significance remains unclear. We previously described novel TTE parameters that outperformed traditional TTE parameters in grading AI severity in these patients., Methods: CF-LVAD patients with varying degrees of AI (N = 57) underwent Doppler TTE of the LVAD outflow cannula. Patients had AI severity graded by the novel parameters (systolic/diastolic velocity ratio and the diastolic acceleration of the LVAD outflow cannula) and the traditional vena contracta. The prognostic performance of novel and traditional AI parameters was determined by comparing rates of congestive heart failure re-admission, need for aortic valve intervention, urgent transplantation and death (composite end-points) for each parameter., Results: Grading AI severity using novel AI parameters led to reclassification of 32% of patients from trace/mild AI to moderate or greater AI (N = 18). Using traditional AI parameters, there was no difference in the occurrence of the composite end-point between the moderate or greater group and the trace/mild group (1.50 vs 1.18 events/person, p = 0.46). With the novel AI parameters, there were significantly more events in the patients with moderate or greater AI compared to those with trace/mild AI (1.57 vs 0.13 events/person, p = 0.002). Novel parameters also better predicted the need for aortic valve intervention, urgent transplantation or death than traditional methods (p = 0.024 vs p = 0.343)., Conclusions: In patients with CF-LVADs, traditional parameters tend to underestimate AI severity and future cardiac events. Novel AI TTE parameters are better able to discriminate AI severity and predict clinically meaningful outcomes., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to develop a technique to measure regurgitant flow throughout the entire cardiac cycle that would more accurately measure aortic insufficiency (AI) severity in patients with continuous-flow left ventricular assist devices (CF-LVADs)., Background: AI is a common problem after CF-LVAD implantation. Current echocardiographic evaluation of AI does not take into account the unique flow properties present in patients with CF-LVADs., Methods: In this prospective study, patients with LVADs who had varying degrees of AI (N = 20) underwent simultaneous right-sided heart catheterization (RHC) and transthoracic echocardiography (TTE). Regurgitant fraction (RF) across the aortic valve was calculated by subtracting the cardiac output obtained using the Fick method from the total systemic flow measured using the sum of the product of the velocity time integral and the cross-sectional area of the LVAD outflow cannula and aortic valve, respectively. The RFs were then compared with the following: 1) traditional TTE grading parameters; and 2) new TTE parameters unique to LVAD physiology, namely the diastolic flow acceleration and the systolic-to-diastolic peak velocity (S/D) ratio of the LVAD outflow cannula., Results: Patients without evidence of AI had an RF approaching zero (2.4 ± 4.6%). Patients with trace and mild AI had an RF of 31.0 ± 5.4%, whereas patients with moderate or severe AI had an RF of 45.8 ± 3.6%. RF correlated better with pulmonary capillary wedge pressure (PCWP) than with vena contracta (correlation coefficient [R] = 0.73 vs. 0.56). The new TTE parameters (S/D ratio and diastolic acceleration) highly correlated with RF (R = 0.91 and 0.94, respectively) and more strongly correlated with PCWP than did vena contracta (R = 0.82 and 0.65 vs. 0.56)., Conclusions: RF measured by simultaneous RHC and TTE better correlates with clinical filling pressures than do traditional TTE parameters and may identify significant AI that could be underestimated using conventional measures. Novel TTE parameters, unique to CF-LVAD physiology, better correlate with RF and filling pressures than do our current TTE measurements., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study tested whether combined invasive hemodynamic and echocardiographic ramp tests can help optimize patient management., Background: Guidelines for optimizing speed and medications in continuous flow ventricular assist device (cfLVAD) patients are mainly based on expert opinion., Methods: Thirty-five cfLVAD patients (21 HeartMate II [Thoratec, Pleasanton, California] and 14 HVAD [HeartWare International, Framingham, Massachusetts]) underwent ramp tests with right heart catheterization (including central venous pressure [CVP], pulmonary artery pressure, pulmonary capillary wedge pressure [PCWP], and blood pressure) and echocardiography. Data were recorded at up to 9 speed settings. Speed changes were in steps of 400 revolutions per minute (RPM) for HeartMate II (8,000 to 12,000 RPM) and 100 RPM for HVAD (2,300 to 3,200 RPM) patients., Results: Only 42.9% of patients had normal CVPs and PCWPs at their original RPM settings. Going from lowest to highest speeds, cardiac output improved by 0.16 ± 0.19 l/min/step (total change 1.28 ± 1.41 l/min) and PCWP decreased by 1.23 ± 0.85 mm Hg/step (total change 9.9 ± 6.5 mm Hg). CVP and systolic blood pressure did not change significantly with RPM. RPM were adjusted based on test results to achieve CVPs and PCWPs as close to normal limits as possible, which was feasible in 56% of patients. For the remainder, results indicated which type of medical management should be pursued., Conclusions: Use of combined hemodynamic and echocardiographic ramp tests in patients provides objective means of optimizing RPM, and has the potential to guide medical management. It remains to be tested whether this strategy has a beneficial impact on quality of life or clinical outcomes., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A subclavian intraaortic balloon pump (SC-IABP) can help to optimize patients with advanced congestive heart failure as a bridge to definitive therapy. We retrospectively reviewed our experience to assess the application and safety of this technique., Methods: We studied 88 patients with decompensated advanced congestive heart failure who received SC-IABP placement between January 2011 and December 2014. The SC-IABP was placed through a graft in the subclavian artery. The intended therapeutic goals for SC-IABP were bridge to transplant (n = 61), mechanical circulatory support (n = 21), or recovery (n = 6). Success was defined as stroke-free survival, achievement of therapeutic goal, and maintenance or improvement in renal function, hemodynamics, and physical conditioning through ambulation and rehabilitation., Results: Eighty patients were successfully bridged to the next therapy (transplant 93.4%, mechanical circulatory support 95.3%, recovery 50%). There was no mortality related to SC-IABP placement. Duration of SC-IABP support was 4 to 135 days (median 21). Failure was attributed to escalation of support (n = 5), stroke (n = 2), and sepsis (n = 1). Mean pulmonary artery pressure significantly improved from 33 ± 11 mm Hg to 28 ± 8 mm Hg (p < 0.05). Eighty-four patients (95.5%) ambulated more than 3 times a day. Two-minute step test demonstrated significant improvement, from 50 ± 9 steps to 90 ± 23 steps (n = 16, p < 0.001). Specific complications of SC-IABP included exchange/repositioning (n = 26, 29.5%), subclavian artery thrombosis (n = 1, 1.1%), and reexploration for hematoma (n = 4, 4.5%) and infection (n = 2, 2.3%). No distal thromboembolic events were observed., Conclusions: The SC-IABP provided excellent hemodynamic support with minimal morbidity and mortality, allowed for extensive rehabilitation, and permitted more than 90% of patients to receive their intended therapy. Therefore, SC-IABP is a compelling bridge device for patients with advanced congestive heart failure., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The renin-angiotensin-aldosterone system (RAAS) plays a critical role in the pathophysiology of heart failure with reduced ejection fraction (HFrEF). Targeting components of the RAAS has produced significant improvements in morbidity and mortality. Angiotensin-converting enzyme (ACE) inhibitors remain first-line therapy for all patients with a reduced ejection fraction. Angiotensin-receptor blockers may be used instead of ACE inhibitors in patients with intolerance, or in conjunction with ACE inhibitors to further reduce symptoms. Recent data support broader indications for aldosterone antagonists in heart failure, and the combination of an ACE-inhibitor and aldosterone antagonist has become the preferred strategy for dual blockade of the RAAS., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Coronary vascular reserve is impaired during acute cellular rejection of the orthotopically transplanted heart, but changes in the peripheral vasculature during rejection have not been well described. To investigate whether peripheral vascular compensatory mechanisms are preserved after orthotopic heart transplantation (OHT), we longitudinally observed systemic vascular resistance (SVR) and cardiac output (CO) during acute cellular rejection. CO decreased during high-grade acute cellular rejection, and maintenance of mean arterial pressure was achieved by increases in SVR, and these changes did not return to baseline until several months after histologic resolution of rejection.

The management of patients awaiting transplantation is a growing concern. This retrospective cohort study examined outcomes of hepatitis C virus (HCV)-infected kidney candidates who remain waitlisted. Records from 315 HCV+ kidney candidates evaluated between 1992 and 2002, were reviewed. A total of 300 (95.1%) patients were receiving renal replacement therapy at evaluation, median duration 48.2 + 4.3 months. The diabetes prevalence was 42.9% in HCV+ candidates, compared to 35.9% among 602 currently listed HCV- patients (p = 0.023). Liver disease, defined by abnormal hepatic biochemistry or histology, was observed in 59% patients. Median post-evaluation follow-up was 1440 +/- 75 days; 138 candidates were transplanted. Kaplan-Meier survival was higher among transplanted than non-transplanted patients (p = 0.003). Of 177 patients not transplanted, 76 were delisted, mostly due to death (45%) and non-compliance (28%), infrequently because of liver disease (8.8%). A Cox regression model was fit to examine risk factors for waitlist death; only diabetes was associated (HR: 2.17, 95% CI: 1.1-4.1, p = 0.02), while liver disease was not. This study demonstrates that, in waitlisted HCV+ kidney patients, diabetes occurs with increased prevalence and is a major mortality determinant. Diabetic HCV+ kidney candidates are therefore a patient subgroup that requires frequent and careful reevaluation to ensure ongoing transplantability.

Objectives: To characterise the inflammatory cell infiltrate in varicose vein wall, and its relationship to the valve complex., Design: A comparative study of the distribution of inflammatory cells in normal and varicose vein., Materials: Specimens of proximal human long saphenous vein were obtained from patients with duplex Doppler confirmed long saphenous vein reflux (n=14). Control vein was obtained from patients undergoing coronary artery bypass without clinical evidence of venous insufficiency (n=6). Longitudinal 7 microm frozen sections of vein, displaying valve, were prepared., Methods: Using immunohistochemistry, T-lymphocytes (CD3), macrophage/monocytes (CD68), neutrophils (CD15s) and mast cells (anti-mast cell tryptase) were identified. The number of cells per unit length vein were counted using light microscopy., Results: There were significantly more mast cells and macrophage/monocytes in varicose vein as compared to control. There was a non-significant trend towards more T-lymphocytes in varicose vein. Few neutrophils were present in varicose or normal vein. The distribution of inflammatory cells with respect to the valve was not found to be significant., Conclusions: Varicose veins display a greater inflammatory cell infiltrate than normal vein. The key role of macrophage/monocytes and mast cells in tissue damage and remodelling should stimulate further research into whether they play a significant role in the development of chronic venous insufficiency.

Objective: To evaluate the relationships between socio-economic and demographic variables and low immunisation coverage at the national level., Methods: The Australian Childhood Immunisation Register (ACIR) contains data at the postcode level on the immunisation status of all children registered with Medicare under the age of seven years. The Australian Bureau of Statistics (ABS) produces a number of indicators of socio-economic status at the postcode level from Census data. These and other ABS demographic data were used to examine the relationship between immunisation coverage and various socio-demographic indicators., Results: Factors associated with lower immunisation uptake differed in rural and metropolitan areas. High levels of education and occupation and a high proportion of Aboriginal residents were significantly associated with lower coverage only in metropolitan postcodes. High unemployment was associated with lower immunisation coverage only in rural postcodes. A high proportion of late starters to immunisation was the strongest single predictor of coverage and was important in rural and metropolitan postcodes. A high proportion of overseas-born persons and of GP-delivered immunisations was also associated with lower coverage in all areas., Conclusions: These data suggest that in metropolitan areas, reasons for low uptake in more advantaged areas require further evaluation. In non-metropolitan areas, low coverage was associated with areas of disadvantage, for which access to services may be more important., Implications: Children who are late in starting the schedule should be targeted.