Improvement in Coronary Allograft Vasculopathy Following Treatment with a Regimen Including Extracorporeal Photophoresis in a Heart Transplant Recipient

Introduction: Extracorporeal photophoresis (ECP) has been used for select heart transplant (HT) recipients with acute cellular rejection, recurrent or refractory rejection, antibody-mediated rejection (AMR) and as prophylactic therapy. Effects of ECP on coronary allograft vasculopathy (CAV) are not as well-described. Case Report: A 48 year-old man with a history of familial cardiomyopathy required left ventricular assist device therapy and ultimately HT in 2001. He developed ISHLT CAV 1 (40% stenosis of LCx and RCA) with severe microvascular dysfunction detected on PET scan (MFR Total 1.14, LAD 1.11, LCx 0.98, RCA 1.40). He was started on treatment with everolimus, but progressive chronic kidney disease necessitated a change back to mycophenolate mofetil. Following this change, his chronic Class II DSA increased significantly and his renal function worsened requiring dialysis, during which time he also had COVID-19. He then presented in cardiogenic shock with ISHLT CAV 3 and pAMR 2 in July 2020 and was treated with an IABP, plasmapheresis, and thymoglobulin. He had recurrent pAMR 2 three months later, for which he was treated with plasmapheresis, bortezomib, rituximab, and ECP. Prior to initiation of ECP, his coronary angiogram demonstrated rapidly progressive ISHLT CAV 3 (80% proximal LAD, 80% ostial LCx, 70% OM1, and 80% mid RCA). Right heart catheterization demonstrated restrictive filling pressures and echocardiogram demonstrated normal graft systolic function. Four months following initiation of ECP therapy, repeat coronary angiography showed improvement of his CAV: the stenosis in the pLAD had regressed to 50%, the proximal LCX stenosis had regressed to 50%, and disease in the distal circumflex artery had also improved (Figure). In our patient, ECP along with multiple other therapies was associated with significant regression of CAV. Even many years post-HT, CAV may be amenable to some therapies.

Remote Monitoring of Heart Transplant Recipients during the COVID-19 Pandemic

Purpose The COVID-19 pandemic created significant challenges in monitoring heart transplant (HT) recipients for rejection due to efforts to minimize contact with the hospital setting. The aim of this study was to evaluate the safety and efficacy of transitioning HT patients to home phlebotomy and a monitoring protocol based on gene expression profiling (GEP) and donor derived cell free DNA (ddcfDNA). Methods A single-center cohort study that prospectively enrolled consecutive HT patients who were transitioned to a remote monitoring protocol employing home phlebotomy and non-invasive surveillance for rejection. Patients were enrolled starting at 2 months post-HT. Positive GEP values were defined as ≥32 (up to 6 months post-HT) and ≥34 (> 6 months post-HT). A positive ddcfDNA score was defined as >0.12%. A positive biopsy was defined as grade ≥1B/1R Results 246 HT patients were enrolled and followed for a minimum of 3 months. Mean age was 56±14, 71.5% were male, and median time from transplant was 2.7 years. The average distance of patients from the hospital was 25.6 miles. 359 blood tests were drawn for detection of GEP and ddcfDNA and 102 biopsies performed (Figure). Among 32 patients who had negative results on both tests and had a biopsy, 0 had a positive biopsy. Of 25 patients who had positive results on both tests and had a biopsy, 3 (12%) had a positive biopsy. The biopsy positivity rate in patients who were GEP+/ddcfDNA- was 6% and in patients who were GEP-/ddcfDNA+ was 8%. None of the positive biopsies were associated with hemodynamic compromise. 15 (6%) of patients were admitted due to allograft rejection during the study period. There were no deaths. Conclusion Using a remote monitoring protocol with home phlebotomy and noninvasive rejection surveillance was feasible and safe in HT recipients. In this cohort, the combination of negative GEP and ddcfDNA scores was accurate at predicting a lack of allograft rejection.

The Utility of Televisits in Heart Transplant Recipients

Purpose In the current era, televisits have become requisite to assess patients and monitor their conditions. Heart transplant (HT) recipients represent a complex population with multiple co-morbidities that require frequent evaluation. This study aimed to assess the effectiveness of televist encounters in a post-heart transplant cohort during the COVID-19 pandemic. Methods This was a prospective cohort study of all HT recipients evaluated via a televist between 3/1/20-5/30/20, at a large academic medical center. Patient demographics, baseline medications and details of televisit encounters were collected from electronic medical records. Patients were followed for 3-months from their first televisit for medication changes, in-person visits, hospital admissions, treated rejection or infection episodes and mortality. Results 301 patients were enrolled, mean age was 56.0±15.1 years and 213 were males (71%). Mean time between transplant and first televisit was 49 months. The number of televisits per patient is seen in Figure 1a. Following-televisits 152 patients (50.5%) had medication changes, mostly immunosuppression (43.5%) followed by diuretics (6.0%). 141 patients (46.8%) were seen in person for either a clinic visit or RHC following a televisit. There were 61 ED visits resulting in 42 admissions in 36 patients (12.0%) (Figure 1b). Of those, 17 occurred within 2 weeks of a televisit (40.5%). There were 8 cardiac related admissions (19.0%, 5 due to treated rejection), 14 (33.3%) due to infection, and 6 due to COVID-19. One patient died due to complications of COVID-19 during the study period. Conclusion In this post HT cohort, there was a high rate of admissions, with most readmissions due to non-cardiac or infectious causes. This study calls into question the role of televisits in this complex patient population and merits further study of how they can best supplement usual care to enhance outcomes in patients post-HT.

The Utility of Televisits in Patients with Cardiac Amyloidosis during the COVID-19 Pandemic

Purpose In the era of COVID-19, the televisit has become a critical means of providing healthcare for patients unable to attend in-person visits. Transthyretin and light chain amyloidosis are complex diseases, that require frequent and close follow up. The aim of this study was to assess the utility and effectiveness of televisit encounters for patients with cardiac amyloidosis (CA) during the COVID-19 pandemic. Methods This was a prospective cohort study of consecutive patients with CA who were evaluated by televisit between March and May, 2020, at a large academic medical center. Patient demographics, baseline medications and details of televisit encounters were collected from electronic medical records. Patients were followed for 3 months from their first televisit for medication changes, in-person clinic visits, hospital admissions, and mortality. Results Ninety-eight patients with CA were included. Mean age was 76.5±9.1 yrs and 79 were male (80.6%). The number of televisits per patient is shown in Figure 1a. Over 3-months follow-up, 26 patients (26.5%) were seen for either an in-person clinic visit or right heart catheterization. There were 7 emergency room visits, of which 4 (4.1%) resulted in hospital admission, 1 patient (1.0%) had multiple admissions and no patient died (Figure 1b). None of the hospital admissions occurred within two weeks of a televisit. Hospital admissions were due to heart failure exacerbation, sepsis, acute kidney injury and dehydration secondary to diarrhea. During follow-up, 23 patients (23.5%) had medication adjustments, most commonly changes in diuretic (56.5%) and mineralocorticoid receptor antagonist (56.5%) doses. Two patients were newly initiated on tafamidis, for treatment of transthyretin CA. Conclusion The use of televisits for the management of patients with CA is feasible, and the low admission rate indicates that televisits are a safe and effective way to manage CA patients in the outpatient setting.

Six-Month Outcomes of Heart Transplant Recipients Infected by COVID-19

Purpose COVID-19 infection might be associated with higher mortality risk for transplanted patients, as a result of their multiple co-morbidities and their immunosuppressed status. We sought to describe the six-month outcomes of heart transplant (HT) recipients infected by COVID-19. Methods We retrospectively analyzed clinical and echocardiographic data from all HT recipients infected with COVID-19 between March and April 2020. All patients were followed for a minimum of 6 months or until death. Results Twenty-eight HT patients were studied, median age was 64 (range 59-69) and 22 were male. Co-morbidities included obesity (25%), diabetes (61%), HTN (71%), CKD (68 %) and chronic lung disease (36%). Eight patients died (29%) (non-survivors) and 20 survived (survivors) COVID-19 infection. All patients who survived the initial hospitalization period remained alive at 6 months (figure 1). There was no difference in the prevalence of co-morbidities between survivors and non-survivors. Survivors had lower peak ferritin (2185 ± 793 vs 18023 ± 16724, p= 0.04) and procalcitonin (0.8 ± 0.3 vs 104 ± 31, p<0.005). Baseline allograft function was similar between survivors and non-survivors and it remained unchanged at 6 months for the survivors’ group (LVEF baseline: 58 ± 1% vs LVEF 6 m 61 ± 3%). Renal function returned to baseline in 85% of survivors at 6 months after hospitalization. Mycophenolate mofetil was held during the acute infection and was resumed after discharge. At 6 months follow-up, all patients returned to their baseline immunosuppression regimen, have no further symptoms of COVID-19 and there have been no subsequent rejection events. Conclusion COVID-19 infection is associated with a high fatality rate (29%) among HT recipients, however, HT recipients that survive the acute COVID-19 infection have preserved allograft function and end-organ function has returned to baseline at 6 months follow-up.