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(1) Background: Cardiac donation after circulatory death (DCD) is an emerging paradigm in organ transplantation. However, this technique is recent and has only been implemented by highly experienced centers. This study compares the characteristics and outcomes of thoraco-abdominal normothermic regional perfusion (TANRP) and static cold-storage DCD and traditional donation after brain death (DBD) cardiac transplants (CT) in a newly stablished transplant program with restricted donor availability. (2) Method: We performed a retrospective, single-center study of all adult patients who underwent a CT between November 2019 and December 2023, with a follow-up conducted until August 2024. Data were retrieved from medical records. A review of the current literature on DCD CT was conducted to provide a broader context for our findings. The primary outcome was survival at 6 months after transplantation. (3) Results: During the study period, 76 adults (median age 56 years [IQR: 50-63 years]) underwent CT, and 12 (16%) were DCD donors. DCD donors had a similar age (46 vs. 47 years, p = 0.727), were mostly male (92%), and one patient had left ventricular dysfunction during the intraoperative DCD process. There were no significant differences in recipients' characteristics. Survival was similar in the DCD group compared to DBD at 6 months (100 vs. 94%) and 12 months post-CT survival (92% vs. 94%), p = 0.82. There was no primary graft dysfunction in the DCD group (9% in DBD, p = 0.581). The median total hospital stay was longer in the DCD group (46 vs. 21 days, p = 0.021). An increase of 150% in transplantation activity due to DCD was estimated. (4) Conclusions: In a new CT program that utilized older donors and included recipients with similar illnesses and comorbidities, comparable outcomes between DCD and DBD hearts were observed. DCD was rapidly incorporated into the transplant activity, demonstrating an expedited learning curve and significantly increasing the availability of donor hearts.

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PURPOSE: In patients with end-stage heart failure who undergo left ventricular assist device (LVAD) implantation, higher pulmonary vascular resistance (PVR) is associated with higher right heart failure rates and ineligibility for heart transplant. Concomitant mitral regurgitation (MR) could potentially worsen pulmonary hemodynamics and lead to worse outcomes; however, its effects in this patient population have not been specifically examined. METHODS: Using an institutional database spanning November 2003 to August 2017, we retrospectively identified patients with elevated PVR who underwent LVAD implantation. Patients were stratified by concurrent MR: moderate/severe (PVR + MR) vs. mild/none (PVR - MR). Cumulative incidence functions and Fine-Gray competing risk regression were performed to assess the effect of MR on heart transplant rates and overall survival during index LVAD support. RESULTS: Of 644 LVAD recipients, 232 (171 HeartMate II, 59 HeartWare, 2 HeartMate III) had baseline PVR > 3 Woods units; of these, 124 (53%) were INTERMACS 1-2, and 133 (57%) had moderate/severe MR (≥ 3 +). Patients with PVR + MR had larger a baseline left ventricular end-diastolic diameter than patients with PVR - MR (87.9 ± 38.2 mm vs. 75.9 ± 38.0 mm; P = 0.02). Median clinical follow-up was 18.8 months (interquartile range: 4.7-36.4 months). Moderate/severe MR was associated with lower mortality rates during index LVAD support (adjusted hazard ratio 0.64, 95% CI 0.41-0.98; P = 0.045) and higher heart transplant rates (adjusted odds ratio 2.86, 95% CI 1.31-6.25; P = 0.009). No differences in stroke, gastrointestinal bleeding, or right heart failure rates were observed. CONCLUSIONS: Among LVAD recipients with elevated preoperative PVR, those with moderate/severe MR had better overall survival and higher transplant rates than those with mild/no MR. These hypothesis-generating findings could be explained by incremental LVAD benefits resulting from reduction of MR and better LV unloading in a subset of patients with larger ventricles at baseline. In patients with preoperative elevated PVR, MR severity may be a prognostic sign that can inform patient selection for end-stage heart failure therapy.

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The late-breaking science presented at the 2023 scientific session of the American Heart Association paves the way for future pragmatic trials and provides meaningful information to guide management strategies in coronary artery disease and heart failure (HF). The dapagliflozin in patient with acute myocardial infarction (DAPA-MI) trial showed that dapagliflozin use among patients with acute MI without a history of diabetes mellitus or chronic HF has better cardiometabolic outcomes compared with placebo, with no difference in cardiovascular outcomes. The MINT trial showed that in patients with acute MI and anemia (Hgb < 10 g/dL), a liberal transfusion goal (Hgb ≥ 10 g/dL) was not superior to a restrictive strategy (Hgb 7-8 g/dL) with respect to 30-day all-cause death and recurrent MI. The ORBITA-2 trial showed that among patients with stable angina and coronary stenoses causing ischemia on little or no antianginal therapy, percutaneous coronary intervention results in greater improvements in anginal frequency and exercise times compared with a sham procedure. The ARIES-HM3 trial showed that in patients with advanced HF who received a HeartMate 3 levitated left ventricular assist device and were anticoagulated with a vitamin K antagonist, placebo was noninferior to daily aspirin with respect to the composite endpoint of bleeding and thrombotic events at 1 year. The TEAMMATE trial showed that everolimus with low-dose tacrolimus is safe in children and young adults when given ≥ 6 months after cardiac transplantation. Providing patients being treated for HF with reduced ejection fraction (HFrEF) with specific out-of-pocket (OOP) costs for multiple medication options at the time of the clinical encounter may reduce 'contingency planning' and increase the extent to which patients are taking the medications decided upon. The primary outcome, which was cost-informed decision-making, defined as the clinician or patient mentioning costs of HFrEF medication, occurred in 49% of encounters with the checklist only control group compared with 68% of encounters in the OOP cost group.

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Ganciclovir, a guanine analogue, is used intravenously (IV) first-line for the prophylaxis and treatment of cytomegalovirus (CMV) infection in solid organ transplant recipients. The pharmacokinetics (PK) of ganciclovir are highly variable, with myelosuppression occurring at high concentrations. Ganciclovir is primarily renally excreted as the parent compound, and clearance is significantly reduced in renal impairment. Acute kidney injury (AKI) is a common post-operative complication of cardiac transplantation, reducing the clearance of ganciclovir. In the intensive care unit (ICU), AKI is often managed by kidney replacement therapy (KRT). One form of KRT, prolonged intermittent kidney replacement therapy (PIKRT) is increasingly used for cost and flexibility advantages. Ganciclovir dosing recommendations are available for varying degrees of renal impairment and KRT, except for PIKRT. In this case of cardiac transplantation, complicated by anuric AKI, a ganciclovir dose of 2.0-2.5 mg/kg of adjusted body weight given after each PIKRT session was demonstrated to achieve PK targets.

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TAF1A, a gene encoding a TATA-box binding protein involved in ribosomal RNA synthesis, is a candidate gene for pediatric cardiomyopathy as biallelic TAF1A variants were reported in two families with affected individuals. Here, we report a third family with two siblings who presented with infantile restrictive cardiomyopathy and carried biallelic missense variants in TAF1A (NM_001201536.1:c.1021G>A p.(Gly341Arg) and c.781A>C p.(Thr261Pro)). Additional shared clinical features in the siblings included feeding intolerance, congenital leukoencephalopathy, ventriculomegaly and concern for primary immunodeficiency. The first-born sibling passed away at 6 months of age due to complications of hemophagocytic lymphohistiocytosis (HLH) whereas the second sibling underwent cardiac transplantation at 1 year of age and is currently well. We compare the clinical and molecular features of all the TAF1A associated cardiomyopathy cases. Our study adds evidence for the gene-disease association of TAF1A with autosomal recessive pediatric cardiomyopathy.

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BACKGROUND: We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy. METHODS: A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events. RESULTS: Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%). CONCLUSIONS: In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.

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A neonate born of third-degree consanguineous marriage presented on day 12 of life with congestive cardiac failure. A male sibling died at 3 months of age, cause of which was not known. He was treated with decongestive measures and multiple inotropes. 2D Echocardiogram revealed severe Left ventricular dysfunction with prominent trabeculations and deep recesses in the left ventricle suggestive of Left ventricular non-compaction. He was also found to have horse-shoe kidney. Considering the presence of cardiac left ventricular non compaction, horse-shoe kidney and family history of neonatal death and pregnancy loss clinical exome sequencing was done. It detected a homozygous missense variant in exon 6 of the AGK gene suggestive of Senger's syndrome. Baby was on regular follow-up and was thriving well on diuretics, sacubitril-valsartan and weekly levosimendan infusions. At 8 months of age, cardiac transplantation was successfully done and baby has been doing well post-transplantation. LVNC in children is rare with an estimated incidence of 0.11 per 100,000, the highest incidence being during infancy. Senger's syndrome is autosomal recessive in inheritance. Senger's syndrome associated with Left ventricular non compaction has been reported only once in literature so far. Renal manifestations in the form of horse shoe kidney like in our index baby has not been reported previously with Senger's syndrome.

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Background/Objectives: Mental health and substance use disorders (MHDs and SUDs) affect cardiac allograft and VAD recipients and impact their quality of life and compliance. Limited research currently exists on MHDs and SUDs in this population. Methods: This study compares the incidence of MHDs and SUDs in the transplant list, VAD, and post-transplant patients with that in heart failure patients. Study cohorts were derived from the TriNetX database using ICD-10 codes. Differences in incidence were examined using the log-rank test. Adults with MHDs and SUDs before the window of time were excluded. All comparisons were made between propensity-matched cohorts. Statistical significance was set at p < 0.05. Results: Transplant waitlist patients showed a significant increase in the incidence of anxiety, depression, panic, adjustment, mood, alcohol use, and eating disorders. Post-transplant patients showed a significant increase in depression and opioid use. VAD patients showed a significant increase in depression and a decrease in panic disorder and anxiety. These results allow for further investigations on prevention and coping strategies. Conclusions: The deterioration of mental health can significantly impact medication compliance, survival, and quality of life. Opioid use for pain management in the early postoperative period should be further investigated to assess its impact on long-term substance use and addiction.

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BACKGROUND: We previously demonstrated that the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statins) play an important role in the regulation of alloimmune responses. However, little is known regarding the effects of statin on allograft protection or donor-specific antibodies (DSA). In this study, we investigated the graft-protective and immunomodulatory effects of rosuvastatin in a model of fully major histocompatibility complex-mismatched murine cardiac allograft transplantation. METHODS: CBA mice underwent transplantation of C57BL/6 (B6) hearts and received 50 and 500 µg/kg/day of rosuvastatin from the day of transplantation until seven days after the completion of transplantation. To confirm the requirement for regulatory T cells (Tregs), we administered an anti-interleukin-2 receptor alpha antibody (PC-61) to rosuvastatin-treated CBA recipients. Additionally, histological and fluorescent staining, cell proliferation analysis, flow cytometry, and DSA measurements were performed. RESULTS: CBA recipients with no treatment rejected B6 cardiac graft acutely (median survival time [MST], 7 days). CBA mice treated with 500 µg/kg/day of rosuvastatin prolonged allograft survival (MSTs, 77 days). Fluorescent staining studies showed that rosuvastatin-treated recipients had strong aggregation of CD4+Foxp3+ cells in the myocardium and around the coronary arteries of cardiac allografts two weeks after grafting. Flow cytometry studies performed two weeks after transplantation showed an increased number of splenic CD4+CD25+Foxp3+ T cells in rosuvastatin-treated recipients. The addition of rosuvastatin to mixed leukocyte cultures suppressed cell proliferation by increasing the number of CD4+CD25+Foxp3+ Tregs. Additionally, Tregs suppressed DSA production in rosuvastatin-treated recipients. CONCLUSION: Rosuvastatin treatment may be a complementary graft-protective strategy for suppressing DSA production in the acute phase, driven by the promotion of splenic and graft-infiltrating CD4+CD25+Foxp3+ Tregs.

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The epidemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had a significant global impact, especially on immunosuppressed populations such as heart transplant recipients. While SARS-CoV-2 initially infects the respiratory system, cardiovascular complications induced by coronavirus disease 2019 (COVID-19) include cardiac arrest, myocardial infarction, heart failure, myocarditis, arrhythmia, acute myocyte injury, thrombotic events, and cardiogenic shock. Here, we present a case of a 45-year-old African American male who tested positive for COVID-19 infection six months after receiving a heart transplant. The patient was asymptomatic initially, but two weeks later he developed dyspnea, early satiety, and abdominal bloating. The patient was admitted to the hospital for acute renal failure and subsequently diagnosed with moderate acute T cell-mediated allograft rejection (Grade 2R) by endomyocardial biopsy. Three months after testing positive for COVID-19, the patient suffered a sudden cardiac death. At autopsy, the epicardium was diffusely edematous and showed vascular congestion. The coronary arteries showed a striking concentric narrowing of lumens and diffusely thickened arterial walls of all major extramural arteries deemed consistent with a rapidly progressive form of cardiac allograft vasculopathy (CAV). SARS-CoV-2 nucleocapsid protein was localized by immunohistochemistry (IHC) in endothelial cells of venules and capillaries within the epicardium. Our localization of SARS-CoV-2 in coronary vessel endothelial cells by IHC suggests that endothelial cell infection, endotheliitis, and immune-related inflammation may be a primary mechanism of vascular injury. The present case represents an early onset rapidly progressive form of CAV. This case may be the first case of post-transplant arteriopathy occurring in such a short time that includes corresponding autopsy, surgical pathology, and IHC data.

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BACKGROUND: Rejection is a major cause of mortality and morbidity in heart transplant (HTx) recipients. Current methods for diagnosing rejection have limitations. Imaging methods to map the entire left ventricle and reliably identify potential sites of rejection is lacking. Animal studies suggest FDG PET-CT (FDG PET) could have potential application in human HTx recipients. METHODS: Between December 2020 and February 2022, all HTx recipients at Harefield Hospital, London, with definite or suspected rejection underwent FDG PET in addition to routine work-up. RESULTS: Thirty HTx recipients (12 with definite and 18 with suspected rejection) underwent FDG PET scans. Overall, 12 of the 30 patients had FDG PET with increased myocardial avidity, of whom 2 died (17%). Eighteen patients of the 30 patients had FDG PET with no myocardial avidity and all are alive (100%, p = 0.15). All patients with definite rejection, scanned within 2 weeks of starting anti-rejection treatment, showed increased myocardial avidity. In 5 cases, FDG PET showed myocardial avidity beyond 6 weeks despite pulsed steroid treatment, suggesting unresolved myocardial rejection. CONCLUSION: Preliminary findings suggest FDG PET may have a role in diagnosing cardiac transplant rejection. Future blinded studies are needed to help further validate this.

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Background: Giant cell myocarditis (GCM) is an inflammatory form of acute heart failure with high rates of cardiac transplantation or death. Standard acute treatment includes multi-drug immunosuppressive regimens. There is a small but growing number of case reports utilizing rabbit anti-thymocyte globulin in severe cases. Case summary: Two cases are presented with similar presentations and clinical courses. Both are middle-aged patients with no significant past medical history, who presented with new acute decompensated heart failure that quickly progressed to cardiogenic shock requiring inotropic and mechanical circulatory support. Both underwent endomyocardial biopsies that diagnosed GCM. Both were treated with a multi-agent immunosuppressive regimen, notably including rabbit anti-thymocyte globulin, with subsequent resolution of shock and recovery of left ventricular ejection fraction. Both remain transplant-free and without ventricular arrhythmias at 7 months and 26 months, respectively. Discussion: In aggregate, these cases are typical of GCM. They add to growing observational data that upfront rabbit anti-thymocyte globulin may reduce morbidity and mortality in GCM, including potentially preventing the need for complex interventions like orthotopic heart transplantation.

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Heart transplantation is a pivotal treatment of end-stage heart failure, and recent advancements have extended median posttransplant life expectancy. However, despite the progress in surgical techniques and medical treatment, heart transplant patients still face complications such as rejection, infections, and drug toxicity. CT is a reliable tool for detecting most of these complications, whereas MR imaging is particularly adept at identifying pericardial pathologies and signs of rejection. Awareness of these nuances by radiologists, cardiologists, and surgeons is desired to optimize care, reduce morbidities, and enhance survival.

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BACKGROUND: Cardiac allograft vasculopathy (CAV) is one of the major late causes of mortality in cardiac transplant recipients beyond the first year. Given the lack of longer term data for PCI in cardiac transplant recipients, we report ten year follow up of such cardiac transplant recipients who underwent PCI at Mayo Clinic. METHODS: A retrospective observational study was conducted that included cardiac transplant recipients who underwent PCI at the Mayo Clinic. Continuous variables were presented as mean (SD) or median (IQR) and discrete variables were presented as frequency (percentage). RESULTS: Thirty-eight consecutive cardiac transplant recipients underwent PCI from January 1, 1995, to June 30, 2023, at the Mayo Clinic. The median age of the cohort was 61.00 years (IQR:51.00-70.00) comprised predominantly of men (65.80%), and 47.40% of the cohort presented with an acute coronary syndrome. The antirejection therapy prior to the PCI included steroids (47.30%), cyclosporine (26.30%), tacrolimus (15.80%), mycophenolate (42.10%), azathioprine (13.10%), & sirolimus (31.57%). Intravascular ultrasound during PCI was utilized in 10.50% of the cases. The median time duration between heart transplant and PCI was 9.00 years (IQR:6.00-13.00 years). Two individuals needed repeat heart transplant for severe CAV. In hospital mortality was 5.20% and the long-term median survival was 7.20 years with a 10-year mortality rate of 65.70%. CONCLUSIONS: This is the first publication reporting ten-year outcomes for PCI in cardiac transplant patients. The salient features for our cohort were a 65.70% mortality rate at 10 years and a median survival of 7.20 years.

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BACKGROUND: Drug overdose (DO) deaths rose to unprecedented levels during the coronavirus disease 2019 (COVID-19) pandemic. This study examines the impact of COVID-19 on the availability of cardiac allografts from DO donors and the implications of DO donor use on recipient survival. METHODS: Heart transplants reported to the United Network for Organ Sharing from January 2017 to November 2019 ("pre-COVID") and from March 2020 to June 2021 ("COVID pandemic") were analyzed with respect to DO donor status. Outcomes were analyzed using Kaplan-Meier survival and Cox regression to identify predictors of survival. Characteristics of discarded cardiac allografts were also compared by DO donor status. RESULTS: During the COVID-19 pandemic, 27.2% of cardiac allografts were from DO donors vs 20.5% pre-COVID, a 32.7% increase (p < 0.001). During the pandemic, DO donors were younger (84.7% vs 76.3% <40 years, p < 0.001), had higher cigarette use (16.1% vs 10.8%, p < 0.001), higher cocaine use (47.4% vs 19.7%, p < 0.001), and higher incidence of hepatitis C antibodies (26.8% vs 6.1%, p < 0.001) and RNA positivity (16.2% vs 4.2%, p < 0.001). While DO donors were less likely to require inotropic support (30.8% vs 35.4%, p = 0.008), they were more likely to have received cardiopulmonary resuscitation (95.3% vs 43.2%, p < 0.001). Recipient survival was equivalent using Kaplan-Meier analysis (log-rank, p = 0.33) and survival probability at 36 months was 85.6% (n at risk = 398) for DO donors vs 83.5% (n at risk = 1,633) for all other donors. Cox regression demonstrated that DO donor status did not predict mortality (hazard ratio 1.05; 95% confidence interval 0.90-1.23, p = 0.53). CONCLUSIONS: During the COVID-19 pandemic, there was a 32.7% increase in heart transplants utilizing DO donor hearts, and DO became the most common mechanism of death for donors. The use of DO donor hearts did not have an impact on short-term recipient survival.

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BACKGROUND: In pediatric heart transplant (PHT), cardiac catheterization with endomyocardial biopsy (EMB) is standard for diagnosing acute rejection (AR) and cardiac allograft vasculopathy (CAV) but is costly and invasive. OBJECTIVES: To evaluate the ability of cardiac magnetic resonance (CMR) to noninvasively identify differences in PHT patients with AR and CAV. METHODS: Patients were enrolled at three children's hospitals. Data were collected from surveillance EMB or EMB for-cause AR. Patients were excluded if they had concurrent diagnoses of AR and CAV, CMR obtained >7days from AR diagnosis, they had EMB negative AR, or could not undergo contrasted, unsedated CMR. Kruskal-Wallis test was used to compare groups: (1) No AR or CAV (Healthy), (2) AR, (3) CAV. Wilcoxon rank-sum test was used for pairwise comparisons. RESULTS: Fifty-nine patients met inclusion criteria (median age 17years [IQR 15-19]) 10 (17%) with AR, and 11 (19%) with CAV. AR subjects had worse left ventricular ejection fraction compared to Healthy patients (p = 0.001). Global circumferential strain (GCS) was worse in AR (p = 0.054) and CAV (p = 0.019), compared to Healthy patients. ECV, native T1, and T2 z-scores were elevated in patients with AR. CONCLUSIONS: CMR was able to identify differences between CAV and AR. CAV subjects had normal global function but abnormal GCS which may suggest subclinical dysfunction. AR patients have abnormal function and tissue characteristics consistent with edema (elevated ECV, native T1 and T2 z-scores). Characterization of CMR patterns is critical for the development of noninvasive biomarkers for PHT and may decrease dependence on EMB.

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Cardiac allograft vasculopathy (CAV) is a significant determinant of long-term survival in heart transplant recipients. Standard CAV screening typically utilizes invasive coronary angiography (ICA). Quantitative flow ratio (QFR) is a computational method for functional testing of coronary stenosis, and may add diagnostic value to ICA in assessing CAV. Consecutive subjects who received heart transplantation and underwent two separate routine coronary angiograms between January 2013 and April 2016 were enrolled. Coronary angiograms and IVUS were performed per local protocol at 1, 2, 3 and 5 years post-transplant. QFR was calculated offline. CAV was assessed semi-quantitively based on coronary angiogram results. Twenty-two patients were enrolled. Mean time from transplant to first included ICA was 2.1 years. QFR in at least 1 coronary vessel was interpretable in 19/22 (86%) of initial ICA (QFR1). QFR1 correlated well with the CAV score derived from the second ICA (CAV2) with a clustering of CAV at lower QFR values. In a receiver-operating characteristic (ROC) analysis, an optimal QFR threshold of 0.88 yielded 0.94 sensitivity and 0.67 specificity (AUC of 0.79) for at least non-obstructive subsequent CAV. Initial angiographically and intravascular ultrasound derived CAV severity poorly predicted subsequent CAV severity. QFR derived from invasive coronary angiography predicts subsequent development of CAV more accurately than angiography and intravascular ultrasound. This novel method of coronary flow assessment in recipients of heart transplantation may be useful to diagnose and predict subsequent CAV development.

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We report the case of a 64-year-old man with a history of chemotherapy-induced cardiomyopathy requiring heart transplant in 2022 who underwent successful endomyocardial biopsy using patient-specific computed tomographic fluoroscopic projections. (Level of Difficulty: Beginner.).