Increasing Utilization of Extended Criteria Donor Hearts for Transplantation: The OCS Heart EXPAND Trial.

BACKGROUND: Extended criteria donor (ECD) hearts available with donation after brain death (DBD) are underutilized for transplantation due to limitations of cold storage. OBJECTIVES: This study evaluated use of an extracorporeal perfusion system on donor heart utilization and post-transplant outcomes in ECD DBD hearts. METHODS: In this prospective, single-arm, multicenter study, adult heart transplant recipients received ECD hearts using an extracorporeal perfusion system if hearts met study criteria. The primary outcome was a composite of 30-day survival and absence of severe primary graft dysfunction (PGD). Secondary outcomes were donor heart utilization rate, 30-day survival, and incidence of severe PGD. The safety outcome was the mean number of heart graft-related serious adverse events within 30 days. Additional outcomes included survival through 2 years benchmarked to concurrent nonrandomized control subjects. RESULTS: A total of 173 ECD DBD hearts were perfused; 150 (87%) were successfully transplanted; 23 (13%) did not meet study transplantation criteria. At 30 days, 92% of patients had survived and had no severe PGD. The 30-day survival was 97%, and the incidence of severe PGD was 6.7%. The mean number of heart graft-related serious adverse events within 30 days was 0.17 (95% CI: 0.11-0.23). Patient survival was 93%, 89%, and 86% at 6, 12, and 24 months, respectively, and was comparable with concurrent nonrandomized control subjects. CONCLUSIONS: Use of an extracorporeal perfusion system resulted in successfully transplanting 87% of donor hearts with excellent patient survival to 2 years post-transplant and low rates of severe PGD. The ability to safely use ECD DBD hearts could substantially increase the number of heart transplants and expand access to patients in need. (International EXPAND Heart Pivotal Trial [EXPANDHeart]; NCT02323321; Heart EXPAND Continued Access Protocol; NCT03835754).

Is it time to stop living in a HeartMate II world?

Despite improving outcomes with modern pump technology, left ventricular assist device (LVAD) utilization for patients with end-stage heart failure (HF) has declined significantly in the preceding half-decade. Here, we examine this trend, noting an inherent contradiction in the declining utilization of an improving therapeutic option. We propose a series of provocative questions as a "call to action" for the field of advanced HF to consider both scientifically and clinically, focusing on our evaluation parameters for LVAD candidacy, our approach to dichotomous LVAD vs transplant decisions, and our current management paradigms. We conclude that modernization in these areas to match the advantages of modern pump technology is required to best serve patients with advanced HF.

Transplantation Outcomes with Donor Hearts after Circulatory Death.

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

Practice patterns of female cardiothoracic surgeons older than age 58 years: Are we making progress?

OBJECTIVE: Women remain a small minority of cardiothoracic surgeons, and within adult cardiac surgery, the gender gap widens. This study examines the career pathway and trajectory of female adult cardiac surgeons. METHODS: Female cardiothoracic surgeons were identified from the American Board of Thoracic Surgery diplomates over 58 years. Publicly available information was obtained to determine years in practice, practice type, academic and leadership title(s), and location of practice. RESULTS: The average number of years in practice for female adult cardiac surgeons was 13.1. Those categorized as adult cardiac surgeons composed 25.4% (n = 90) of all female cardiothoracic diplomates and 134 (37.9%) were categorized as other subspecialty practice. Of the adult cardiac surgeons, 33.3% (n = 30) practiced privately and the remainder in academic practice. Academic titles were held by 47.8% (43 out of 90) and 30% (27 out of 90) held a position of leadership. Of those in academic practice, 25% (11 out of 42) are titled professor, whereas 43% (18 out of 42) are assistant professors. Most commonly, those in positions of leadership held the title "director," which reflects 37% (10 out of 27) of individuals. Practice locations were distributed throughout the United States, with the highest number in the northeast (26.7%). CONCLUSIONS: Only a small portion of female cardiothoracic surgeons pursue a career in adult cardiac surgery compared to their male counterparts. From 1999 to 2009, 1300 individuals were board certified cardiothoracic surgeons, of whom only 103 (7.9%) were female. Of these, the majority of female cardiothoracic surgeons entered academic practice. Although the overall number of practicing female adult cardiac surgeons has increased with a growth rate of 10.7%, this number remains extremely low. A discrepancy remains between gender representation of academic titles and leadership positions. Although the field has increased female representation over the past few decades, work remains to ensure all potential talent is encouraged and supported.

Unconventional use of total artificial heart in a patient with severe, destructive prosthetic valve endocarditis.

Here, we report the case of a patient who presented to our institution with severe, destructive, and unreconstructable prosthetic valve endocarditis which required the planned implantation of a total artificial heart (TAH) to function as a bridge to cardiac transplantation. The use of TAH in this fashion has been infrequently reported in the literature. This case highlights the importance of a thoughtful, preoperative multidisciplinary approach to these complex patients to provide the most appropriate and life-saving care.

Survival after orthotopic heart transplantation in patients with BMI > = 35 with and without diabetes.

BACKGROUND: Orthotopic heart transplant (OHT) recipients with a body mass index (BMI) > = 35 have worse survival than those with a BMI < 35. Diabetes is a risk factor for mortality. We evaluated the impact of diabetes on mortality rates after OHT in patients with a BMI > 35. METHODS: Patients > 18 years who underwent OHT 2008-2017 with a BMI > = 35 were identified in the United Network for Organ Sharing (UNOS) database. Recipient and donor characteristics were compared. A Kaplan Meier analysis was performed. A multivariable Cox proportional hazards model examined the relationship between diabetes and survival. The equivalence of survival outcomes was examined by an unadjusted Cox proportional hazards model and the two one-sided test procedure, using a pre-specified equivalence region. RESULTS: Patients with diabetes were older, had a higher creatinine, lower bilirubin, fewer months on the waitlist, and the donor was less likely to be on inotropes. Kaplan-Meier analysis showed no difference in patient survival. Recipient factors associated with an increased risk of death were increasing bilirubin and machine ventilation. Increasing ischemic time resulted in an increased hazard of death. Long-term survival outcomes were equivalent. CONCLUSIONS: In OHT recipients with a BMI > 35, there is no statistical difference in longterm survival in recipients with or without diabetes. These results encourage continued consideration for OHT in patients BMI > 35 with coexisting diabetes.

Coronary angiography utilization in the evaluation of a potential heart donor by age: a narrative review.

Heart transplant is the gold standard treatment for patients with heart failure. The limitation to providing heart transplantation to patients suffering from end stage heart disease is the stable organ supply within the United States despite increasing demand. Transplant centers across the United States have begun to expand traditional cardiac donor selection metrics previously utilized. As a result, the use of extended criteria donors, such as older donors, those with longer ischemic times, and donors considered high risk has increased. Current guidelines suggest that coronary angiography be performed when evaluating a donor above the age of 45. Angiographic guidelines for evaluation of the donor heart are based specifically on age, with little evidence based guidance surrounding the use of angiography in a younger donor with comorbidities or increased risk behavior which may lead to premature coronary artery disease. Recently, we have seen an increase in younger heart donors, many of whom have succumbed due to drug overdose with ensuing high risk behaviors. Given the increased risk nature of these donors, consideration of performing coronary angiography is determined by clinical "gestalt" of the transplant center evaluating the heart for use, which may lead to underutilization of donor organs without evidence to support the practice. Here, we review the guidelines, literature, and controversy surrounding the use of coronary angiography in evaluating donor hearts for transplantation.

Left ventricular assist device implantation by bi-thoracotomy technique: A single-center perspective.

BACKGROUND: Left ventricular assist devices (LVAD) are standardly implanted via full sternotomy. Nonsternotomy approaches are gaining popularity, but potential benefits of this approach have not been well-studied. We hypothesized that LVAD implantation by bi-thoracotomy (BT) would demonstrate smaller and more consistent inflow cannula angles leading to improved postoperative outcomes compared to sternotomy. METHODS: Charts of patients who underwent LVAD implantation between June 2018 and June 2020 at a single academic institution were retrospectively reviewed. Patient demographics, surgical approach (sternotomy vs. BT), laboratory values, and postoperative course were compared. The inflow cannula angle was measured on the first chest radiograph available postoperatively. RESULTS: Of 40 patients studied, BT approach was used in 17 (42.5%). Mean inflow cannula angles were smaller in BT patients (23.0 vs. 37.1 degrees, p = .018) and had a smaller standard deviation (13.8 vs. 20.3). Excluding patients who went on to receive a heart transplant or died in the same hospitalization, there was no difference in median length of hospital stay after surgery (16.0 vs. 17.5 days, p = .768). However, BT patients required fewer days of postoperative inotrope support (4.0 vs. 7.0 days, p = .012). CONCLUSIONS: Our data suggest inflow cannula angles are smaller and more consistent with the BT approach, which leads to a shorter duration of postoperative inotropic support. This finding may suggest improved right heart function following LVAD implant via BT approach. Further study is warranted to determine additional benefits of the BT approach.

MicroRNA-21 regulates right ventricular remodeling secondary to pulmonary arterial pressure overload.

Right ventricular (RV) function is a critical determinant of survival in patients with pulmonary arterial hypertension (PAH). While miR-21 is known to associate with vascular remodeling in small animal models of PAH, its role in RV remodeling in large animal models has not been characterized. Herein, we investigated the role of miR-21 in RV dysfunction using a sheep model of PAH secondary to pulmonary arterial constriction (PAC). RV structural and functional remodeling were examined using ultrasound imaging. Our results showed that post PAC, RV strain significantly decreased at the basal region compared with t the control. Moreover, such dysfunction was accompanied by increases in miR-21 levels. To determine the role of miR-21 in RV remodeling secondary to PAC, we investigated the molecular alteration secondary to phenylephrine induced hypertrophy and miR21 overexpression in vitro using neonatal rat ventricular myocytes (NRVMs). We found that overexpression of miR-21 in the setting of hypertrophic stimulation augmented only the expression of proteins critical for mitosis but not cytokinesis. Strikingly, this molecular alteration was associated with an eccentric cellular hypertrophic phenotype similar to what we observed in vivo PAC animal model in sheep. Importantly, this hypertrophic change was diminished upon suppressing miR-21 in NRVMs. Collectively, our in vitro and in vivo data demonstrate that miR-21 is a critical contributor in the development of RV dysfunction and could represent a novel therapeutic target for PAH associated RV dysfunction.

Successful heart transplantation in a patient who recovered from COVID-19.

Coronavirus disease-2019 has created unprecedented challenges for society, and specifically the medical community. While the pandemic continues to unfold, the transplant community has had to pivot to keep recipients, donors, and institutional transplant teams safe given the unique circumstances inherent to solid organ transplantation.