Heart transplantation: advances in expanding the donor pool and xenotransplantation.

Approximately 65 million adults globally have heart failure, and the prevalence is expected to increase substantially with ageing populations. Despite advances in pharmacological and device therapy of heart failure, long-term morbidity and mortality remain high. Many patients progress to advanced heart failure and develop persistently severe symptoms. Heart transplantation remains the gold-standard therapy to improve the quality of life, functional status and survival of these patients. However, there is a large imbalance between the supply of organs and the demand for heart transplants. Therefore, expanding the donor pool is essential to reduce mortality while on the waiting list and improve clinical outcomes in this patient population. A shift has occurred to consider the use of organs from donors with hepatitis C virus, HIV or SARS-CoV-2 infection. Other advances in this field have also expanded the donor pool, including opt-out donation policies, organ donation after circulatory death and xenotransplantation. We provide a comprehensive overview of these various novel strategies, provide objective data on their safety and efficacy, and discuss some of the unresolved issues and controversies of each approach.

Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19.

BACKGROUND: Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. OBJECTIVES: We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. METHODS: Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. RESULTS: Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent. CONCLUSIONS: Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079).

A case report of acute heart failure and cardiogenic shock caused by catastrophic antiphospholipid syndrome and lupus myocarditis.

Background: Catastrophic antiphospholipid syndrome and lupus myocarditis are two rare life-threatening conditions. Case summary: We present a case of a 47-year-old woman admitted in profound cardiogenic shock due to catastrophic antiphospholipid syndrome and lupus myocarditis requiring advanced heart failure therapies, including early mechanical circulatory support. She improved with steroids, immunoglobulins, mycophenolate, and eculizumab. Discussion: This case highlights the importance of early identification of cardiogenic shock secondary to catastrophic antiphospholipid syndrome and lupus myocarditis, the arrhythmogenic complications of myocarditis, and the subsequent management of the disease progression with mechanical and medical support.

De novo human leukocyte antigen allosensitization patterns in patients bridged to heart transplantation using left ventricular assist devices.

INTRODUCTION: We examined the impact and time course of de novo human leukocyte antigen (HLA) allosensitization following left ventricular assist device (LVAD) implantation. METHODS AND RESULTS: Forty patients had a calculated panel reactive antibody (cPRA) prior to LVAD surgery between January 2014 and December 2018. Of these patients, we retrospectively studied 33 patients who had pre-LVAD cPRA <10%. De novo allosensitization was defined as cPRA ≥10% within 3 months following LVAD surgery, and "persistent allosensitization" was defined as cPRA ≥10% at time of heart transplant or death. One-third (11/33) of our cohort developed de novo allosensitization within 3-months post-LVAD. Median duration of follow-up during LVAD support was 588 days (IQR 337-1071 days), or approximately 19 months. In an adjusted, multivariable analysis, female sex remained associated with de novo allosensitization (adjusted odds ratio [95%CI]: 11 (1.4-85), P = 0.026). De novo allosensitization was subsequently associated with persistent allosensitization (P = 0.024). Both axial-flow and centrifugal-flow LVADs had similar rates of allosensitization. Compared to those with no allosensitization, patients with de novo allosensitization did not appear to have inferior post-transplant outcomes of death or treated rejection. CONCLUSION: In our single-center experience, one-third of patients developed de novo allosensitization which did not appear to associate with inferior post-transplant outcomes. Female sex was associated with de novo allosensitization.

Relation of Left Ventricular Assist Device Infections With Cardiac Transplant Outcomes.

Left ventricular assist device (LVAD)-specific infections (LSIs) are common in patients on LVAD support awaiting heart transplant (HT), yet their impact on post-HT outcomes is not completely understood. We hypothesized that LSIs would result in vasoplegia and negatively affect post-HT 30-day and 1-year outcomes. LSI was defined as driveline, pump, or pocket infection. The short-term outcome was a composite of acute renal failure, allograft rejection, and mortality at 30 days after HT. The long-term outcome was a composite of allograft rejection and death within 1 year after HT. We performed a retrospective analysis of 111 HT recipients bridged with durable LVAD support at our institution from May 2012 to August 2019. Of these, 63 patients had LSIs, with 94% of the infections being driveline infections. Vasoplegia was more prevalent in the LSI group but not significantly (7 vs 2 persons, p = 0.3). There was no difference in the composite end point of acute renal failure, rejection, or death at 30 days (30% vs 25%, p = 0.55) or 1-year end point of rejection and death (38% vs 40%, p = 0.87) in patients with LSI versus those without LSI. In conclusion, LSIs were common in patients on LVAD who underwent HT in our single-center contemporary cohort. However, LSI was not associated with adverse outcomes at 30 days or at 1 year after HT.

Racial and ethnic differences in severity of coronary calcification among patients undergoing PCI: Results from a single-center multiethnic PCI registry.

BACKGROUND: Although population-based studies have demonstrated racial heterogeneity in coronary artery calcium (CAC) burden, the degree to which such associations extend to percutaneous coronary intervention (PCI) cohorts remains poorly characterized. We sought to evaluate the associations between race/ethnicity and CAC in a PCI population. METHODS: This single center retrospective study analyzed 1025 patients with prior CAC who underwent PCI between January 1, 2012 and May 15, 2020. Patients were grouped as non-Hispanic White (NHW, N = 779), non-Hispanic Black (NHB, N = 81) and Hispanic (H, N = 165). Associations between race and CAC (Agatston units) were examined using negative binomial regression while adjusting for baseline parameters. RESULTS: Among the 1025 patients (mean age 65.8, 70% male) who underwent PCI, NHW, NHB, and H populations had median CAC scores of 760, 500, and 462 Agatston units, respectively (p < 0.0001). Hispanic patients displayed a higher burden of diabetes mellitus, hypertension and hyperlipidemia compared with other groups. After adjusting for baseline differences and compared with NHW, the inverse association between Hispanic and CAC persisted (ß = -324.1, p < 0.0001) whereas differences were not significant for NHB (ß = -51.5, p = 0.67). CONCLUSIONS: Despite a higher risk clinical phenotype, Hispanic patients who underwent PCI had significantly lower CAC compared with non-Hispanic patients. Thus, current risk stratification models using universalized CAC scores may underestimate the risk for the Hispanic population. Race/ethnicity-informed CAC thresholds may better guide clinical decisions.

Prognostic Value of Electrocardiographic QRS Diminution in Patients Hospitalized With COVID-19 or Influenza.

During the clinical care of hospitalized patients with COVID-19, diminished QRS amplitude on the surface electrocardiogram (ECG) was observed to precede clinical decompensation, culminating in death. This prompted investigation into the prognostic utility and specificity of low QRS complex amplitude (LoQRS) in COVID-19. We retrospectively analyzed consecutive adults admitted to a telemetry service with SARS-CoV-2 (n = 140) or influenza (n = 281) infection with a final disposition-death or discharge. LoQRS was defined as a composite of QRS amplitude <5 mm or <10 mm in the limb or precordial leads, respectively, or a ≥50% decrease in QRS amplitude on follow-up ECG during hospitalization. LoQRS was more prevalent in patients with COVID-19 than influenza (24.3% vs 11.7%, p = 0.001), and in patients who died than survived with either COVID-19 (48.1% vs 10.2%, p <0.001) or influenza (38.9% vs 9.9%, p <0.001). LoQRS was independently associated with mortality in patients with COVID-19 when adjusted for baseline clinical variables (odds ratio [OR] 11.5, 95% confidence interval [CI] 3.9 to 33.8, p <0.001), presenting and peak troponin, D-dimer, C-reactive protein, albumin, intubation, and vasopressor requirement (OR 13.8, 95% CI 1.3 to 145.5, p = 0.029). The median time to death in COVID-19 from the first ECG with LoQRS was 52 hours (interquartile range 18 to 130). Dynamic QRS amplitude diminution is a strong independent predictor of death over not only the course of COVID-19 infection, but also influenza infection. In conclusion, this finding may serve as a pragmatic prognostication tool reflecting evolving clinical changes during hospitalization, over a potentially actionable time interval for clinical reassessment.

Pancytopenia caused by allopurinol and azathioprine interaction in a heart transplant patient: a case report.

BACKGROUND: Azathioprine is an immunosuppressive now less commonly prescribed after orthotopic heart transplantation. Patients with solid organ transplantation are at increased risk for numerous comorbidities including gout. Co-administration of allopurinol for gout prophylaxis and azathioprine increases the risk for severe myelosuppression due to drug-drug interactions. CASE SUMMARY: A 57-year-old male with a history of heart transplant 6 years prior presented with a month of severe fatigue and shortness of breath. His admission laboratory values were notable for severe pancytopenia. Medical workup revealed no haematologic malignancy, viral infection, or other consumptive process. After extensive review, it was discovered that the patient was taking excessive allopurinol for gout. His haematologic abnormalities resolved following discontinuation of allopurinol and treatment with filgrastim and romiplostim and was able to be discharged from the hospital. DISCUSSION: Azathioprine and allopurinol can potentially cause profound cytopenias due to the increased production of the active metabolites of azathioprine. Given the association between gout and solid organ transplantation, recognition of the risks of medication interaction as well as communication amongst health care providers and between providers and their patients is paramount.

Alumni Perspectives on the Role of Medical School Service Learning Experiences in Their Professional Development and Practice.

PURPOSE: Understand how participation in service-learning activities in medical school influenced physicians' early careers. METHODS: Researchers conducted semi-structured interviews with physicians who had completed residency training and held leadership positions within an established medical-student-run, service-learning initiative. The research team analyzed the interviews iteratively, using an editing coding strategy to identify categories, and identified themes by prolonged data immersion. The team sought disconfirming evidence and conducted member-checking. Researchers stopped interviews after no new themes emerged (saturation). RESULTS: The research team identified four main themes: service-learning activities provided an outlet for individuals predisposed to service; participants reported actively seeking underserved populations in their practice; participants described increased sensitivity towards the underserved; and participants reported gaining leadership, organizational, and administrative skills. CONCLUSIONS: Physicians who participated in medical school service-learning activities indicated these experiences influenced their professional development and approach to practice. Future studies may consider these outcomes when evaluating service-learning projects.