Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

HFSA Expert Consensus Statement on the Medical Management of Patients on Durable Mechanical Circulatory Support.

The medical management of patients supported with durable continuous flow left ventricular assist device (LVAD) support encompasses pharmacological therapies administered in the preoperative, intraoperative, postoperative, and chronic LVAD support stages. As patients live longer on LVAD support, the risks of LVAD-related complications and progression of cardiovascular and other diseases increase. Using existing data from cohort studies, registries, randomized trials, and expert opinion, this Heart Failure Society of America Consensus Document on the Medical Management of Patients on Durable Mechanical Circulatory Support offers best practices on the management of patients on durable mechanical circulatory support, focusing on pharmacological therapies administered to patients on continuous flow LVADs. Although quality data in the LVAD population are few, the use of guideline-directed heart failure medical therapies and the importance of blood pressure management, right ventricular preload and afterload optimization, and antiplatelet and anticoagulation regimens are discussed. Recommended pharmacological regimens used to mitigate or treat common complications encountered during LVAD support, including arrhythmias, vasoplegia, mucocutaneous bleeding, and infectious complications, are addressed. Finally, this document touches on important potential pharmacological interactions from antidepressants and herbal and nutritional supplements of relevance to providers of patients on LVAD support.

Impact of Donor Hemodynamics on Recipient Survival in Heart Transplantation.

BACKGROUND: Heart transplantation is the gold-standard therapy for end-stage heart failure, but rates of donor-heart use remain low due to various factors that are often not evidence based. The impact of donor hemodynamics obtained via right-heart catheterization on recipient survival remains unclear. METHODS: The United Network for Organ Sharing registry was used to identify donors and recipients from September 1999-December 2019. Donor hemodynamics data were obtained and analyzed using univariate and multivariable logistical regression, with the primary endpoints being 1- and 5-year post-transplant survival. RESULTS: Of the 85,333 donors who consented to heart transplantation during the study period, 6573 (7.7%) underwent right-heart catheterization, of whom 5531 eventually underwent procurement and transplantation. Donors were more likely to undergo right-heart catheterization if they had high-risk criteria. Recipients who had donor hemodynamic assessment had 1- and 5-year survival rates similar to those without donor hemodynamic assessment (87% vs 86%, 1 year). Abnormal hemodynamics were common in donor hearts but did not impact recipient survival rates, even when risk-adjusted in multivariable analysis. CONCLUSIONS: Donors with abnormal hemodynamics may represent an opportunity to expand the pool of viable donor hearts.

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial.

IMPORTANCE: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. OBJECTIVE: To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. DESIGN, SETTING, and PARTICIPANTS: This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. Intervention: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. MAIN OUTCOMES AND MEASURES: The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. RESULTS: Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. CONCLUSIONS AND RELEVANCE: In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.

A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report.

BACKGROUND: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. METHODS: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).

Exploring Physician Perceptions of the 2018 United States Heart Transplant Allocation System.

BACKGROUND: After the implementation of the 2018 US heart transplant allocation system, the experience and perceptions of heart transplant clinicians have not been well-cataloged. METHODS AND RESULTS: This web-based survey of both heart failure cardiologists and surgeons examined physician perspectives about the policy changes and whether the system is meeting its intended goals. The majority of participants (94%, n = 113) responded that the 2018 heart allocation system requires modification. Eighty-four percent reported using more temporary mechanical circulatory support to achieve higher status and 86% were concerned about the change in physician behavior and practices under the new system. CONCLUSIONS: Suggestions for possible improvement included higher status for patients on durable left ventricular assist device support, changes to criteria for status 2, modification of status exceptions, and advocacy for a heart allocation score.

Increased Opportunities for Transplantation for Women in the New Heart Allocation System.

BACKGROUND: Historically, women have had less access to advanced heart failure therapies, including temporary and permanent mechanical circulatory support and heart transplantation (HT), with worse waitlist and post-transplant survival compared with men. This study evaluated for improvement in sex differences across all phases of HT in the 2018 allocation system. METHODS AND RESULTS: The United Network for Organ Sharing registry was queried to identify adult patients (≥18 years) listed for HT from October 18, 2016, to October 17, 2018 (old allocation), and from October 18, 2018, to October 18, 2020 (new allocation). The outcomes of interest included waitlist survival, pretransplant use of temporary and durable mechanical circulatory support, rates of HT, and post-transplant survival. There were 15,629 patients who were listed for HT and included in this analysis; 7745 (2039 women, 26.3%) in the new and 7875 patients (2074 women, 26.3%) in the old allocation system. When compared with men in the new allocation system, women were more likely to have lower priority United Network for Organ Sharing status at time of transplant, and less likely to be supported by an intra-aortic balloon pump (27.1% vs 32.2%, P < .001), with no difference in the use of venoarterial extracorporeal membrane oxygenation (5.5% vs 6.3%, P = .28). Despite these findings, when transplantation was viewed in the context of risk for death or delisting, the cumulative incidence of transplant within 6 months of listing was higher in women than men in the new allocation system (62.4% vs 54.9%, P < .001) with no differences in post-transplant survival. When comparing women in the old with the new allocation system, the distance traveled for organ procurement was 187.5 ± 207.0 miles vs 272.8 ± 233.7 miles (P < .001). CONCLUSIONS: Although the use of temporary mechanical circulatory support in women remains lower than in men in the new allocation system, more women are being transplanted with comparable waitlist and post-transplant outcomes as men. Broader sharing may be making its greatest impact on improving transplant opportunities for women.

A Novel Model Incorporating Pectoralis Muscle Measures to Predict Mortality After Ventricular Assist Device Implantation.

BACKGROUND: We have previously demonstrated that pectoralis muscle mass and tissue attenuation obtained on preoperative CT scans were powerful predictors of mortality after left ventricular assist device implantation. In this analysis, we confirm our findings in a separate left ventricular assist device implantation cohort, and we present a novel, user-friendly mortality-prediction model incorporating these measures. METHODS AND RESULTS: Patients with chest CTs performed ≤ 3 months prior to left ventricular assist device implantation at University of Minnesota (n = 143) and Houston Methodist Hospital (n = 133) were identified. Unilateral pectoralis muscle mass indexed to body surface area (PMI) and attenuation (approximated by mean Hounsfield units) (PHUm) were measured on preoperative chest CT scans. To develop a prediction model incorporating pectoralis muscle measures, we implemented a cross-validated model-selection approach using Cox proportional hazards regression models. The final model included PHUm, PMI, African American race, creatinine, total bilirubin, body mass index, bridge to transplant, and presence or absence of contrast. Receiver-operating characteristic curves for 30-, 90- and 365-day survival were generated. The area under the curve for the model at 30, 90 and 365 days was 0.78, 0.76 and 0.76, respectively. CONCLUSIONS: The Minnesota Pectoralis Risk Score had favorable discrimination in this multicenter dataset. These skeletal-muscle measures appear to add important information to preoperative risk assessment.

Nonsustained ventricular tachycardia in heart failure with preserved ejection fraction.

BACKGROUND: Ventricular tachycardia (VT) is a common arrhythmia in heart failure with reduced ejection fraction but its incidence, predictors, and significance have not been determined in heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a retrospective review of arrhythmias in two cohorts of patients with an HFpEF diagnosis. Patients in cohort 1 (n = 40) underwent routine arrhythmia surveillance with a 14-day ambulatory electrocardiogram (ECG) monitor. Patients in cohort 2 (n = 85) had cardiac pacemakers and underwent routine device interrogations. RESULTS: In cohort 1, 13 patients (32.5%) had one or more episodes of nonsustained VT (NSVT) on ambulatory ECG. In cohort 2, 38 patients (44.7%) had NSVT on cardiac pacemaker interrogations. During a median (interquartile range) follow-up of 3.0 (1.6 to 5.1) years, 15 (12%) patients died (20% of patients with NSVT versus 6.8% of those without NSVT; P = .03). In logistic regression analysis, NSVT was associated with a 3.4-fold higher odds of death (95% confidence interval 1.08 to 10.53; P = .04) in HFpEF. CONCLUSIONS: In conclusion, patients with HFpEF have a relatively high, and possibly underappreciated, burden of NSVT, which confers a higher risk of mortality. The frequent episodes of NSVT in these patients may provide insight into the mechanism of sudden cardiac death in HFpEF.

Clinical characteristics and organ system involvement in sarcoidosis: comparison of the University of Minnesota Cohort with other cohorts.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Clinical cohort studies of different populations are important to understand the high variability in clinical presentation and disease course of sarcoidosis. The aim of the study is to evaluate clinical characteristics, including organ involvement, pulmonary function tests, and laboratory parameters, in a sarcoidosis cohort at the University of Minnesota. We compare the organ system involvement of this cohort with other available cohorts. METHODS: We conducted a retrospective data collection and analysis of 187 subjects with biopsy-proven sarcoidosis seen at a tertiary center. Organ system involvement was determined using the WASOG sarcoidosis organ assessment instrument. Clinical phenotype groups were classified using the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis criteria. RESULTS: Mean subject age at diagnosis was 45.8 ± 12.4, with a higher proportion of males (55.1%), and a higher proportion of blacks (17.1%) compared to the racial distribution of Minnesota residents (5.95%). The majority (71.1%) of subjects required anti-inflammatory therapy for at least 1 month. Compared to the A Case Control Etiologic Study of Sarcoidosis cohort, there was a higher frequency of extra-thoracic lymph node (34.2% vs. 15.2%), eye (20.9% vs. 11.8%), liver (17.6% vs. 11.5%), spleen (20.9% vs. 6.7%), musculoskeletal (9.6% vs. 0.5%), and cardiac (10.7% vs. 2.3%) involvement in our cohort. A multisystem disease with at least five different organs involved was identified in 13.4% of subjects. A restrictive physiological pattern was observed in 21.6% of subjects, followed by an obstructive pattern in 17.3% and mixed obstructive and restrictive pattern in 2.2%. Almost half (49.2%) were Scadding stages II/III. Commonly employed disease activity markers, including soluble interleukin-2 receptor and angiotensin-converting enzyme, did not differ between treated and untreated groups. CONCLUSIONS: This cohort features a relatively high frequency of high-risk sarcoidosis phenotypes including cardiac and multiorgan disease. Commonly-utilized serum biomarkers do not identify subpopulations that require or do better with treatment. Findings from this study further highlight the high-variability nature of sarcoidosis and the need for a more reliable biomarker to predict and measure disease severity and outcomes for better clinical management of sarcoidosis patients.

How to Develop and Implement a Specialized Heart Failure with Preserved Ejection Fraction Clinical Program.

Heart failure with preserved ejection fraction (HFpEF), a highly prevalent and complex clinical syndrome with high morbidity and mortality, is often unrecognized and not optimally treated. Clinical trials for HFpEF have been plagued by low enrollment, and clinicians often approach HFpEF patients with "therapeutic nihilism" given the perceived lack of available therapies based on the disappointing results of these prior trials. Due to these challenges, we have pioneered the successful creation of dedicated, specialized HFpEF clinical programs. Here, we discuss (1) the rationale for the development of a specialized HFpEF clinical program; (2) strategies for the systematic identification of HFpEF patients; (3) a standardized diagnostic and therapeutic approach; (4) validation of the HFpEF clinical program paradigm; (5) staffing and reimbursement considerations; (6) HFpEF clinical trial enrollment; and (7) challenges and future directions for HFpEF clinical programs. We conclude that it is feasible to create HFpEF clinical programs that fulfill the major unmet need of identifying and caring for patients with HFpEF. These clinics are essential for confirming the HFpEF diagnosis, providing standardized treatment, and facilitating clinical trial enrollment. It is our hope that the information provided here will encourage others to establish their own specialized HFpEF programs, thereby allowing for comprehensive care for these complex patients.