Denial for Advanced Heart Failure Therapies Due to Psychosocial Stressors: Who Comes Back?

BACKGROUND: Psychosocial evaluations to assess candidacy for advanced heart failure therapies are not standardized across institutions, potentially contributing to disparities in approval for advanced therapies. Remediation rates of psychosocial stressors among patients with advanced HF and reconsideration for advanced therapies have not been well described. METHODS AND RESULTS: We performed a retrospective, single-center study of 647 adults evaluated for heart transplant and VAD between 2014 and 2020, of whom 89 (14%) were denied for psychosocial stressors including caregiver, substance use, housing, financial, or mental health concerns. Later reevaluation occurred in 32 (36%) patients, of whom 23 were then approved. Patients initially declined were mostly male (76%), white (74%), and urban (79%). Reevaluation occurred in more women than men (43% vs 34%), black patients than white (43% vs 37%), and urban patients than rural (39% vs 28%). Patients had fewer psychosocial stressors at reevaluation (median=0.5) than at initial denial (median=2). Caregiver and substance use concerns were the most prevalent stressors in patients never returning for or subsequently denied at reevaluation. CONCLUSIONS: Caregiver and substance use concerns were common in patients denied for psychosocial reasons. Future efforts should focus on early screening for these stressors and implementation of a systematic reevaluation process.

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era.

BACKGROUND: Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre-direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test-positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. METHODS AND RESULTS: We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. CONCLUSIONS: These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

Outcomes of Heart Transplant Donation After Circulatory Death.

BACKGROUND: Heart transplantation using donation after circulatory death (DCD) allografts is increasingly common, expanding the donor pool and reducing transplant wait times. However, data remain limited on clinical outcomes. OBJECTIVES: We sought to compare 6-month and 1-year clinical outcomes between recipients of DCD hearts, most of them recovered with the use of normothermic regional perfusion (NRP), and recipients of donation after brain death (DBD) hearts. METHODS: We conducted a single-center retrospective observational study of all adult heart-only transplants from January 2020 to January 2023. Recipient and donor data were abstracted from medical records and the United Network for Organ Sharing registry, respectively. Survival analysis and Cox regression were used to compare the groups. RESULTS: During the study period, 385 adults (median age 57.4 years [IQR: 48.0-63.7 years]) underwent heart-only transplantation, including 122 (32%) from DCD donors, 83% of which were recovered with the use of NRP. DCD donors were younger and had fewer comorbidities than DBD donors. DCD recipients were less often hospitalized before transplantation and less likely to require pretransplantation temporary mechanical circulatory support compared with DBD recipients. There were no significant differences between groups in 1-year survival, incidence of severe primary graft dysfunction, treated rejection during the first year, or likelihood of cardiac allograft vasculopathy at 1 year after transplantation. CONCLUSIONS: In the largest single-center comparison of DCD and DBD heart transplantations to date, outcomes among DCD recipients are noninferior to those of DBD recipients. This study adds to the published data supporting DCD donors as a safe means to expand the heart donor pool.

Early Blood Pressure Variables Associated With Improved Outcomes in VA-ECLS: The ELSO Registry Analysis.

BACKGROUND: As utilization of veno-arterial extracorporeal life support (VA-ECLS) in treatment of cardiogenic shock (CS) continues to expand, clinical variables that guide clinicians in early recognition of myocardial recovery and therefore, improved survival, after VA-ECLS are critical. There remains a paucity of literature on early postinitiation blood pressure measurements that predict improved outcomes. OBJECTIVES: The objective of this study is to help identify early blood pressure variables associated with improved outcomes in VA-ECLS. METHODS: The authors queried the ELSO (Extracorporeal Life Support Organization) registry for cardiogenic shock patients treated with VA-ECLS or venovenous arterial ECLS between 2009 and 2020. Their inclusion criteria included treatment with VA-ECLS or venovenous arterial ECLS; absence of pre-existing durable right, left, or biventricular assist devices; no pre-ECLS cardiac arrest; and no surgical or percutaneously placed left ventricular venting devices during their ECLS runs. Their primary outcome of interest was the survival to discharge during index hospitalization. RESULTS: A total of 2,400 CS patients met the authors' inclusion criteria and had complete documentation of blood pressures. Actual mortality during index hospitalization in their cohort was 49.5% and survivors were younger and more likely to be Caucasian, intubated for >30 hours pre-ECLS initiation, and had a favorable baseline SAVE (Survival After Veno-arterial ECMO) score (P < 0.05 for all). Multivariable regression analyses adjusting for SAVE score, age, ECLS flow at 4 hours, and race showed that every 10-mm Hg increase in baseline systolic blood pressure (HR: 0.92 [95% CI: 0.89-0.95]; P < 0.001), and baseline pulse pressure (HR: 0.88 [95% CI: 0.84-0.91]; P < 0.001) at 24 hours was associated with a statistically significant reduction in mortality. CONCLUSIONS: Early (within 24 hours) improvements in pulse pressure and systolic blood pressure from baseline are associated with improved survival to discharge among CS patients treated with VA-ECLS.

Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion.

BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation and the growing interest in donation after circulatory death (DCD), our institution recently began procuring cardiac allografts from DCD donors. METHODS: Between October 2020 and March 2021, 15 patients with heart failure underwent cardiac transplantation using DCD allografts. Allografts were procured using a modified extracorporeal membrane oxygenation circuit for thoracic normothermic regional perfusion (TA-NRP) and were subsequently transported using cold static storage. Data collection and analysis were performed with institutional review board approval. RESULTS: The mean age of the DCD donors was 23 ± 7 years and average time on TA-NRP was 56 ± 8 minutes. Total ischemic time was 183 ± 31 minutes and distance from transplant center was 373 ± 203 nautical miles. Recipient age was 55 ± 14 years, with 8 (55.3%) recipients on durable left ventricular assist device support. Post-transplant, 6 (40%) recipients experienced mild left ventricle primary graft dysfunction (PGD-LV), 3 (20%) recipients experienced moderate PGD-LV, and no recipients experienced severe PGD-LV. Postoperative transthoracic echocardiogram demonstrated left ventricular ejection fraction >55% in all recipients. One recipient (6.6%) developed International Society for Heart and Lung Transplantation 2R acute cellular rejection on first biopsy. At last follow-up, all 15 recipients were alive past 30-days. CONCLUSIONS: Cardiac DCD provides an opportunity to increase the availability of donor hearts for transplantation. Utilizing TA-NRP with cold static storage, we have extended the cold ischemic time of DCD allografts to almost 3 hours, allowing for inter-hospital organ transport.

Impact of increased donor distances following adult heart allocation system changes: A single center review of 1-year outcomes.

BACKGROUND: On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes. METHODS: In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006). CONCLUSIONS: Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed.

Trends in Renal Function Among Heart Transplant Recipients of Donor-Derived Hepatitis C Virus.

Donor-derived hepatitis C (dd-HCV) infection may increase the risk of renal impairment (RI) among heart transplantation (HT) recipients. Sofosbuvir, an integral component of HCV direct-acting antivirals (DAAs) has also been linked to RI. To date, no study has examined the trends in renal function for HT recipients of dd-HCV infection and assessed safety and efficacy of Sofosbuvir-based DAAs. Between September 2016 and June 2018, 46 HCV-naive patients and one patient with a history of HCV treated pretransplant, underwent HT from HCV-positive donors (follow-up available through October 10, 2018). Patients were treated with Ledipasvir-Sofosbuvir (genotype 1) or Sofosbuvir-Velpatasvir (genotype 3) for 12 or 24 weeks; no dose adjustments were made for renal function. Data on renal function were available for 23 patients who achieved a sustained virologic response at 12 weeks after the treatment (SVR12; cohort A) and 18 patients who completed 1 year of follow-up (cohort B). Treatment of dd-HCV infection was initiated at a median of 6 weeks post-HT. In both cohorts, a nonsignificant reduction in median estimated glomerular filtration rate (eGFR; ml/min/1.73 m) was noted (cohort A: pretransplant eGFR: 62 [interquartile range {IQR}: 1-84] to SVR12 eGFR: 49 [IQR: 37-82]; p = 0.43; cohort B: pretransplant eGFR: 65 [IQR: 54-84] to 1 year post-HT eGFR: 56 [IQR: 39-75]; p = 0.29). Pretreatment renal function had no significant impact on changes in renal function during treatment. All patients tolerated DAAs well with 100% completion rate to the assigned therapy and duration and 100% success at achieving SVR12. In this first and largest reported case series to date of HT recipients with dd-HCV infection, we observed that neither the dd-HCV infection nor its treatment with Sofosbuvir-based DAAs increased the risk of RI. Sofosbuvir-based DAAs appear safe, tolerable, and effective for HCV treatment even in presence of severe RI.

Expanding Heart Transplant in the Era of Direct-Acting Antiviral Therapy for Hepatitis C.

Importance: For patients awaiting heart transplant, hepatitis C-positive donors offer an opportunity to expand the donor pool, shorten wait times, and decrease wait-list mortality. While early reported outcomes among few heart transplant recipients have been promising, knowledge of 1-year outcomes in larger cohorts of patients is critical to shared decision-making with patients about this option. Objective: To better define the association of hepatitis C-positive donors with heart transplant volumes, wait-list duration, the transmission and cure of donor-derived hepatitis C, and morbidity and mortality at 1 year. Design, Setting, and Participants: This was a prospective, single-center observational study of 80 adult (age 18 years or older) patients who underwent heart transplant using hearts from hepatitis C-positive donors between September 2016 and April 2019 at a large academic medical center. Among donors, who were considered hepatitis C-positive if results from hepatitis C antibody and/or nucleic acid testing were positive, 70 had viremia and 10 were seropositive but did not have viremia. Follow-up was available through May 15, 2019. Comparisons were drawn with patients who underwent transplant with hearts from hepatitis C-negative donors during the same period. Exposures: In addition to standard posttransplant management, transplant recipients who developed donor-derived hepatitis C infection were treated with direct-acting antivirals. Main Outcomes and Measures: The main outcomes included wait-list duration and 1-year survival in all patients, and for those who developed donor-derived hepatitis C, the response to direct-acting antiviral treatment. Results: Of 80 patients, 57 (71.3%) were men, 55 (68.7%) were white, and 17 (26.3%) were black; the median age at transplant was 54.5 years (interquartile range, 46-62 years). Following consent to accept hearts from hepatitis C-exposed donors, the median days to heart transplant was 4 (interquartile range, 1-18). No recipients of donors with negative nucleic acid testing results (10 [12.5%]) developed donor-derived hepatitis C. Of 70 patients who were recipients of donors with positive nucleic acid testing results, 67 (95.7%) developed donor-derived hepatitis C over a median follow-up of 301 days (interquartile range, 142-617). Treatment with direct-acting antivirals was well tolerated and yielded sustained virologic responses in all treated patients. Within the cohort with infection, 1-year patient survival was 90.4%, which was not significantly different compared with the cohort without infection or with patients who received transplants from hepatitis C-negative donors during the same period. Conclusions and Relevance: In the era of direct-acting antivirals, hepatitis C-positive donors are a viable option to expand the donor pool, potentially reducing wait-list duration and mortality. In heart transplant recipients with donor-derived hepatitis C, infection is well-tolerated and curable, and 1-year survival is equivalent to that in recipients of hepatitis C-negative donors.

Anticoagulation Reversal and Risk of Thromboembolic Events Among Heart Transplant Recipients Bridged with Durable Mechanical Circulatory Support Devices.

Anticoagulation reversal agents (ARAs) can minimize bleeding complications associated with mechanical circulatory support devices (MCSDs) explantation at the time of heart transplantation (HT); data on thromboembolic (TE) risk associated with ARAs are limited in this patient population. In this single-center study, we retrospectively analyzed 118 consecutive adults who were supported with durable MCSDs and underwent HT between May 2013 and October 2016. Patients were categorized based on intraoperative use of ARAs (recombinant factor VIIa [n=23], 4-factor prothrombin complex concentrate [n=48], or factor IX complex [n=2]) at the time of HT; these agents were used at discretion of implanting surgeons for bleeding control. The primary outcome of interest was presence of venous or systemic TE events within 3 months of HT. Multivariable logistic regression analyses were used to assess association between TE events and use of ARAs. A total of 71 (60%) patients received ARAs, and a total of 32 patients (27.1%) had TE events (25 venous [median time to diagnosis: 11.5 days; interquartile range {IQR}: 9-31 days], and 10 systemic [median time to diagnosis: 5.5 days; IQR: 4-8 days]); 26 (81.2%) of those with TE events had ARAs used at the time of HT. Multivariable analysis identified use of ARAs as an independent predictor of TE events (multivariable odds ratio: 3.06; 95% CI: 1.09-8.58; p = 0.034). Unplanned intraoperative use of ARAs to control bleeding was associated with a significantly higher risk of TE events among HT recipients bridged with durable MCSD. Future studies are required to further assess safety of these agents and their impact on patient outcomes.

Center volume and post-transplant survival among adults with congenital heart disease.

BACKGROUND: The number of adult congenital heart disease (ACHD) patients requiring heart transplantation (HT) continues to grow, and if they survive the first year after transplant, their long-term survival is at least equivalent to non-ACHD patients. The 1-year survival of ACHD patients with HT remains lower than non-ACHD patients. We evaluated the affect of transplant center volume on 1-year survival of ACHD patients. We analyzed United Network of Organ Sharing patients (age ≥18 years) who underwent their first orthotopic HT between January 1, 2000, and December 31, 2015, to assess the association between transplant center volume and 1-year survival of ACHD patients. RESULTS: We identified 827 ACHD patients at 113 centers who underwent HT during the study period. The average age of the recipients and donors was 36 ± 13 years (60% men and 84% Caucasian) and 28 ± 11 (63% men and 66% Caucasian), respectively. Of the ACHD patients undergoing HT, 27% (n = 60) were done at low-volume centers, 30% (n = 10) were reported at high-volume centers, and the remaining (n = 43) were at medium-volume centers. A total of 96 patients died within 30 days, including 37 (16.7%) at low-volume, 37 (10.2%) at medium-volume, and 22 (9.0%) at high-volume centers (p = 0.019). The average unadjusted Kaplan-Meier 30-day survival at low-volume centers was 83% ± 2%, which was significantly lower than medium-volume (90% ± 1%) and high-volume (91% ± 2%) centers (log-rank p < 0.05). Within 1 year, 154 patients had died, including 56 (36.4%) at low-volume, 60 (38.9%) at medium-volume, and 38 (24.7%) at high-volume centers (p = 0.011). Average unadjusted Kaplan-Meier 1-year survival at low-volume centers was 75% ± 3%, which was significantly lower than medium-volume (83% ± 2%) and high-volume (84% ± 2%) centers (log-rank p < 0.05). CONCLUSIONS: The 30-day and 1-year survival of ACHD patients undergoing HT is partly influenced by overall transplant center volume and, potentially, volume of ACHD HTs, with low-volume centers performing poorly relative to medium-volume and high-volume centers. The role of peri-operative care and multidisciplinary management in improving survival at low-volume centers required further investigations.

Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies.

BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. METHODS: Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval. RESULTS: At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients. CONCLUSIONS: In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.