Background: The impact of COVID-19 on heart transplant (HTx) recipients remains unclear, particularly in the early post-transplant period. Methods: We share novel insights from our experience in five HTx patients with COVID-19 (three within 2 months post-transplant) from our institution at the epicenter of the pandemic. Results: All five exhibited moderate (requiring hospitalization, n = 3) or severe (requiring ICU and/or mechanical ventilation, n = 2) illness. Both cases with severe illness were transplanted approximately 6 weeks before presentation and acquired COVID-19 through community spread. All five patients were on immunosuppressive therapy with mycophenolate mofetil (MMF) and tacrolimus, and three that were transplanted within the prior 2 months were additionally on prednisone. The two cases with severe illness had profound lymphopenia with markedly elevated C-reactive protein, procalcitonin, and ferritin. All had bilateral ground-glass opacities on chest imaging. MMF was discontinued in all five, and both severe cases received convalescent plasma. All three recent transplants underwent routine endomyocardial biopsies, revealing mild (n = 1) or no acute cellular rejection (n = 2), and no visible viral particles on electron microscopy. Within 30 days of admission, the two cases with severe illness remain hospitalized but have clinically improved, while the other three have been discharged.

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Introduction: Acute heart failure (AHF) is a leading cause of hospitalization and readmission in the US. The present study evaluated maximum diuresis while minimizing electrolyte imbalances, hemodynamic instability, and kidney dysfunction, to achieve a euvolemic state safely in a shorter period of time. Methods and results:A protocol of combined therapy with furosemide, metolazone, and spironolactone, with or without tolvaptan and acetazolamide, was used in 17 hospitalized patients with AHF. The mean number of days on combination diuretic protocol was 3.8 days. The mean daily fluid balance was 3.0±2.1 L negative. The mean daily urine output (UOP) was 4.1±2.0 L (range 1.8-10.5 L). There were minimal fluctuations in serum electrolyte levels and serum creatinine over the duration of diuretic therapy. There was no statistically significant change in patients' creatinine from immediately prior to therapy to the last day of therapy, with a mean increase in creatinine of 0.14 mg/dL (95% CI −0.03, +0.30, p=0.10). Conclusion: Our strategy of treating AHF by achieving high UOP, while maintaining stable electrolytes and creatinine in a short period to euvolemic state, is safe.

Introduction: Cytokine release syndrome (CRS) and associated cardiovascular (CV) events are common following infusion of chimeric antigen receptor T cell therapy (CAR-T). There are no data characterizing whether CAR-T recipients with a pre-existing cardiac dysfunction (LVEF <53%) are at increased risk for CV events following CAR-T. Hypothesis: We hypothesized that cardiac dysfunction would be associated with a higher rate of CV events following CAR-T infusion. CV events were defined as a composite of cardiogenic shock, clinical heart failure, myocardial infarction, or arrhythmia. Methods: Patients in a multi-center registry of adult CAR-T recipients with a known baseline LVEF were included (n=241). Covariates included standard baseline CV and cancer parameters. Results: In total, 22 (9%) CAR-T patients had a pre-existing cardiac dysfunction. Those with and without [219 (91%)] baseline cardiac dysfunction were similar in age, gender, pre-existing CV risk factors, and ECOG performance status. LVEF among patients with cardiac dysfunction ranged from 25%-52%. There was no difference in prior anthracycline use, cancer type or burden, but cardiac dysfunction patients had higher rates of prior radiation (36% vs 16%, p=0.02). Cardiac dysfunction patients received less investigational CAR-T (9% vs 31%, p=0.03), more tisagenlecleucel (36% vs 18%, p=0.04), and had similar rates of axicabtagene ciloleucel and lisocabtagene maraleucel. There was no difference in mean CRS grade, rate of ≥2 grade CRS, or in tocilizumab or steroids use between those with and without cardiac dysfunction. During a median follow-up of 294 (IQR 123-661) days, 60 (25%) patients experienced CV events with more events in patients with cardiac dysfunction (63% vs 21%, p<0.001). In a Cox model adjusted for covariates identified in univariate analyses, baseline cardiac dysfunction was independently associated with an increased CV events risk (adjusted HR: 4.9, 95% CI 2.54–9.61, p<0.001) Conclusions: CAR-T recipients with pre-existing cardiac dysfunction experience more CV events despite similar rates of CRS.

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