Goswami, Rohan

Background: International data on COVID-19 infection in immunosuppressed populations is limited. Heart transplant (OHT) recipients requiring immunotherapy are at risk for potentially increased complications with COVID-19 infection, including long-covid and oxidative stress during initial infection. The availability of vaccination and temporal trends in this population has not been well described. We report outcomes in immunosuppressed patients during the initial years of the COVID pandemic. Methods: All patients who underwent heart transplantation at Mayo Clinic in Florida were reviewed from March 2019 to October 2021. Patients were divided into two groups: those diagnosed with COVID-19 (based on a positive SARS-CoV-2 RT-PCR) and those not. A p value of 0.05 was considered significant using the Chi-squared test. Results: A total of 98 patients were reviewed. Of these, 49 were COVID-19-positive (CP), and 49 were negative (CN). The cohort was well matched, with a median age of 58 years (49 - 65) in both groups. 20 females in the CP group and 9 in the CN group. Diabetic status (p = .07), history of hypertension (p=.5), BMI (p=.41), GFR (p=.19), and ejection fraction (p=.29) were not significantly different between the two groups. Immunosuppression was not significantly different for CP or CN patients, with a median trough tacrolimus level of 7.68 vs. 8.70 (p = .26). The median time from transplant to CP was 384 days (237 - 677). The CN group’s median follow-up after transplant was 947 days (737 - 1191). CP hospitalization rate was 24% (5 Pfizer, 3 unvaccinated, 4 Moderna) with only 1 death. Hospitalized patients’ markers of inflammation were: IL6 19.2 (12-48), D-dimer 1408 (763 - 2227), and CRP 54 (20 - 90). The CP group was more vaccinated than the CN group (92% vs. 78%, p = .025). More CP patients received the Pfizer vaccine compared to Moderna (p = .018). Conclusion: We found that patients after OHT on similar immunotherapy regimens did not carry the same risk of contracting Covid-19 despite being vaccinated. CP patients were generally infected in the first 1.5 years after OHT. This may indicate an increased infection rate due to a weakened immune system or lack of bivalent boosters before 2022. Vaccine efficacy in this population should be evaluated in larger studies.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia detected in hospitalized patients. It is independently associated with an increased risk of stroke. Anti-fibrotic properties of mineralocorticoid receptor antagonists (MRA) have been proposed to modulate AF burden. Gender differences in patients with AF exist within the epidemiology and causative mechanisms to outcomes and complications. We compared men and women with known AF while treated with MRA to assess potential differences in stroke rate. Method: After IRB approval, we performed a retrospective chart review of all patients with confirmed HF and AF diagnoses. Patient data were extracted from electronic medical records. Patients with AF and HF treated with MRA were included in this study. Results: 64 patients with HF and AF treated with MRA were reviewed between January 2021 and September 2022. 34 were male, and 30 were female. Females were younger, 66 years (57 -74) compared to males, 73 years (60 - 78), p=.13. The median ejection fraction was similar among women, 42% (31 - 50) compared to men, 41% (33 - 49), p = .43. A significantly higher incidence of atrial fibrillation was found in our male group (59%) compared to the female group (30%), p=.02. There was no significant difference in MRA or anticoagulation use between male and female patients (p = .11, p = .12 respectively). More men had strokes compared to females (16% vs. 26% p = .17). Men were also more likely to be hypertensive compared to females (47% vs. 25%, p<.01). Conclusion: Men were more likely to have AF and stroke compared to females with HF on MRA therapy. Males were more likely to be hypertensive, which may relate to increased stroke rate in this patient population. Increased awareness of the gender-based prevalence of stroke rate in patients with HF and AF may allow for earlier recognition and reduction in stroke events.

Background: Inclisiran is a first-in-class, cholesterol-lowering small interfering RNA based therapy for treatment of atherosclerosis or familial hypercholesterolemia as an adjunct to maximally tolerated statin therapy. Since approval by FDA in December 2021, it is getting increasingly popular due to biannual regimen. During trials and upon review for FDA approval, it exhibited injection site reaction, arthralgia, urinary tract infection, diarrhea, and dyspnea. Objective: In view of increased usage, it is important to establish a side effect profile of inclisiran in general population since the ORION 9, 10 and 11 trials. Methods: We explored reported adverse events (AEs) of inclisiran using FDA Adverse Event Reporting System (FAERS). A total of 472 AEs were reported until September 2022. 44.49% AEs were reported by healthcare professionals (HCPs), which were further analyzed. AEs were analyzed in men (35.2%) vs women (45.2%) and in three age groups of 18-64, 65-85, and >85 years. Results: A total of 100 (47%) events were serious including 38% hospitalization and 14% deaths. The most frequently reported AE was surprisingly dyspnea in conjunction with cough (21.9%) followed by myalgia (15.2%), injection site pain (5.2%), arthralgia (4.3%), diarrhea (4.3%), rash (3.3%) and fatigue (2.4%). Most AEs were consistent with ORION trial except elevated LDL (8.2%), acute myocardial infarction (AMI) (7.6%), hyponatremia (6.6%), acute kidney injury (AKI) (3.3%) and headache (2.4%). It was reported more in women of age group 65-85 years. Discussion: The events of death and hospitalization after initiating inclisiran could have been associated with AMI, AKI and hyponatremia that are newly reported since the trial, however the temporality and mechanisms are unknown. Even though the trial has shown that this drug is relatively safe, physicians must be vigilant about the new developments to avoid decompensation in vulnerable patients. Its use in patients with pulmonary disease can worsen dyspnea. Conclusion: With the current increasing use of inclisiran, there is a need for more data on safety profile. In future, further randomized trials are required to better assess the safety profile focusing on temporality and mechanisms of AMI and AKI in relation to inclisiran.

The Impella® (Abiomed; Danvers, MA) pumps are percutaneous, transvalvular mechanical circulatory support (MCS) devices that propel blood from left ventricle to aorta that are used to augment cardiac output in management of high-risk percutaneous coronary intervention (HRPCI), acute heart failure, or cardiogenic shock. These systems utilize a flow of purge fluid that runs countercurrent to the blood flow which prevents inline thrombosis and protein deposition. Guidelines generally recommend heparin-dextrose purge fluid, with BBPS reserved for patients with heparin intolerance or active bleeding. We present the first case of use of BBPS as an elective choice for purge fluid in a patient with severe cardiogenic shock.Patient is 56-year-old male with known history of hypertension, diabetes and hyperlipidemia who presented with acute onset shortness of breath secondary to acute heart failure in the setting of myocardial infarction. He underwent a HRPCI for a non revascularizable three vessel coronary artery disease. He was readmitted for cardiogenic shock complicated with ventricular tachycardia, fibrillation and high risk of sudden cardiac death, necessitating inpatient transplant evaluation. Left heart catheterization showed pulmonary artery pressure of 59/63, wedge of 29 and cardiac index of 2 on 0.125mcg/kg/hr of milrinone. He received aggressive diuresis, antiarrhythmics and inotropic support. With increasing milrinone requirement, Impella 5.5 was placed and his antiplatelet regimen was changed from oral prasugrel to intravenous cangrelor with aspirin. A clinical decision was made to use BBPS instead of heparin purge, based on institutional experience and clinical data. Purge pressure, flow, lactate dehydrogenase and hematocrit have remained stable about 1.5ml/hr, 500mm Hg, 230U/L and 30% respectively for 22 days post-impella placement as the patient awaits transplantation.Limited retrospective studies and animal data, have shown no change in purge pressure/flow with BBPS. However, most of the data remains limited to use in heparin-intolerant patients. Our experience has indicated the possibility to use BBPS without systemic anticoagulation with no short-term complication,however conclusive trial data needs to be generated.

Abstract Aims We sought to investigate the outcomes of heart transplant patients supported with Impella 5.5 temporary mechanical circulatory support. Methods and results Patient demographics, perioperative data, hospital timeline, and haemodynamic parameters were followed during initial admission, Impella support, and post-transplant period. Vasoactive-inotropic score, primary graft failure, and complications were recorded. Between March 2020 and March 2021, 16 advanced heart failure patients underwent Impella 5.5 temporary left ventricular assist device support through axillary approach. Subsequently, all these patients had heart transplantation. All patients were either ambulatory or chair bound during their temporary mechanical circulatory support until heart transplantation. Patients were kept on Impella support median of 19 days (3–31) with the median lactate dehydrogenase level of 220 (149–430). All Impella devices were removed during heart transplantation. During Impella support, patients had improved renal function with median creatinine serum level of 1.55 mg/dL decreased to 1.25 (P = 0.007), pulmonary artery pulsatility index scores increased from 2.56 (0.86–10) to 4.2 (1.3–10) (P = 0.048), and right ventricular function improved (P = 0.003). Patients maintained improved renal function and favourable haemodynamics after their heart transplantation as well. All patients survived without any significant morbidity after their heart transplantation. Conclusions Impella 5.5 temporary left ventricular assist device optimizes care of heart transplant recipients providing superior haemodynamic support, mobility, improved renal function, pulmonary haemodynamics, and right ventricular function. Utilizing Impella 5.5 as a direct bridging strategy to heart transplantation resulted in excellent outcomes.