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Acute Myocarditis Associated With Desmosomal Gene Variants

Ammirati, Enrico; Raimondi, Francesca; Piriou, Nicolas; Sardo Infirri, Loren; Mohiddin, Saidi A; Mazzanti, Andrea; Shenoy, Chetan; Cavallari, Ugo A; Imazio, Massimo; Aquaro, Giovanni Donato; Olivotto, Iacopo; Pedrotti, Patrizia; Sekhri, Neha; Van de Heyning, Caroline M; Broeckx, Glenn; Peretto, Giovanni; Guttmann, Oliver; Dellegrottaglie, Santo; Scatteia, Alessandra; Gentile, Piero; Merlo, Marco; Goldberg, Randal I; Reyentovich, Alex; Sciamanna, Christopher; Klaassen, Sabine; Poller, Wolfgang; Trankle, Cory R; Abbate, Antonio; Keren, Andre; Horowitz-Cederboim, Smadar; Cadrin-Tourigny, Julia; Tadros, Rafik; Annoni, Giuseppe A; Bonoldi, Emanuela; Toquet, Claire; Marteau, Lara; Probst, Vincent; Trochu, Jean Noël; Kissopoulou, Antheia; Grosu, Aurelia; Kukavica, Deni; Trancuccio, Alessandro; Gil, Cristina; Tini, Giacomo; Pedrazzini, Matteo; Torchio, Margherita; Sinagra, Gianfranco; Gimeno, Juan Ramón; Bernasconi, Davide; Valsecchi, Maria Grazia; Klingel, Karin; Adler, Eric D; Camici, Paolo G; Cooper, Leslie T
BACKGROUND:The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown. OBJECTIVES/OBJECTIVE:The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV. METHODS:In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up. RESULTS:In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. CONCLUSIONS:Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk.
PMID: 36175056
ISSN: 2213-1787
CID: 5334522

Long-term follow-up of acute and chronic rejection in heart transplant recipients from hepatitis C viremic (NAT+) donors

Stachel, Maxine W; Alimi, Marjan; Narula, Navneet; Flattery, Erin E; Xia, Yuhe; Ramachandran, Abhinay; Saraon, Tajinderpal; Smith, Deane; Reyentovich, Alex; Goldberg, Randal; Kadosh, Bernard S; Razzouk, Louai; Katz, Stuart; Moazami, Nader; Gidea, Claudia G
The long-term safety of heart transplants from hepatitis C viremic (NAT+) donors remains uncertain. We conducted a prospective study of all patients who underwent heart transplantation at our center from January 2018 through August 2020. Routine testing was performed to assess for donor-derived cell-free DNA, acute cellular rejection (ACR), antibody-mediated rejection (AMR), and cardiac allograft vasculopathy (CAV). Allograft dysfunction and mortality were also monitored. Seventy-five NAT- recipients and 32 NAT+ recipients were enrolled in the study. All NAT+ recipients developed viremia detected by PCR, were treated with glecaprevir/pibrentasvir at the time of viremia detection, and cleared the virus by 59 days post-transplant. Patients who underwent NAT testing starting on post-operative day 7 (NAT+ Group 1) had significantly higher viral loads and were viremic for a longer period compared with patients tested on post-operative day 1 (NAT+ Group 2). Through 3.5 years of follow-up, there were no statistically significant differences in timing, severity, or frequency of ACR in NAT+ recipients compared with the NAT- cohort, nor were there differences in noninvasive measures of graft injury, incidence or severity of CAV, graft dysfunction, or mortality. There were five episodes of AMR, all in the NAT- group. There were no statistically significant differences between Group 1 and Group 2 NAT+ cohorts. Overall, these findings underscore the safety of heart transplantation from NAT+ donors.
PMID: 36053676
ISSN: 1600-6143
CID: 5332222

Pre-transplant immune cell function assay as a predictor of early cardiac allograft rejection

Maidman, Samuel D; Gidea, Claudia; Reyentovich, Alex; Rao, Shaline; Saraon, Tajinderpal; Kadosh, Bernard S; Narula, Navneet; Carillo, Julius; Smith, Deane; Moazami, Nader; Katz, Stuart; Goldberg, Randal I
INTRODUCTION/BACKGROUND:ImmuKnow, an immune cell function assay that quantifies overall immune system activity can assist in post-transplant immunosuppression adjustment. However, the utility of pre-transplant ImmuKnow results representing a patient's baseline immune system activity is unknown. This study sought to assess if pre-transplant ImmuKnow results are predictive of rejection at the time of first biopsy in our cardiac transplant population. METHODS:This is a single center, retrospective observational study of consecutive patients from January 1, 2018 to October 1, 2020 who underwent orthotopic cardiac transplantation at NYU Langone Health. Patients were excluded if a pre-transplant ImmuKnow assay was not performed. ImmuKnow results were categorized according to clinical interpretation ranges (low, moderate, and high activity), and patients were divided into two groups: a low activity group versus a combined moderate-high activity group. Pre-transplant clinical characteristics, induction immunosuppression use, early postoperative tacrolimus levels, and first endomyocardial biopsy results were collected for all patients. Rates of clinically significant early rejection (defined as rejection ≥ 1R/1B) were compared between pre-transplant ImmuKnow groups. RESULTS:Of 110 patients who underwent cardiac transplant, 81 had pre-transplant ImmuKnow results. The low ImmuKnow activity group was comprised of 15 patients, and 66 patients were in the combined moderate-high group. Baseline characteristics were similar between groups. Early rejection occurred in 0 (0%) patients with low pre-transplant ImmuKnow levels. Among the moderate- high pre-transplant ImmuKnow group, 16 (24.2%) patients experienced early rejection (P = .033). The mean ImmuKnow level in the non-rejection group was the 364.9 ng/ml of ATP compared to 499.3 ng/ml of ATP for those with rejection (P = .020). CONCLUSION/CONCLUSIONS:Patients with low pre-transplant ImmuKnow levels had lower risk of early rejection when compared with patients with moderate or high levels. Our study suggests a possible utility in performing pre-transplant ImmuKnow to identify patients at-risk for early rejection who may benefit from intensified upfront immunosuppression as well as to recognize those where slower calcineurin inhibitor initiation may be appropriate.
PMID: 35678734
ISSN: 1399-0012
CID: 5279542

Results of Heart Transplants from Donation After Circulatory Death (DCD) Donors Using Thoraco-Abdominal Normothermic Regional Perfusion (TA-NRP) Compared to Donation After Brain Death ( [Meeting Abstract]

Gidea, C G; James, L; Smith, D; Carillo, J; Reyentovich, A; Saraon, T; Rao, S; Goldberg, R; Kadosh, B; Ngai, J; Piper, G; Narula, N; Moazami, N
Purpose: In the U.S., heart transplantation from donation after circulatory death (DCD) is increasing. We present our institutional experience of DCD transplantation by using a thoracoabdominal-normothermic regional perfusion (TA-NRP) protocol and compare the results to a cohort concomitantly transplanted, from standard brain death (
ISSN: 1557-3117
CID: 5240352

Longitudinal Echocardiographic Assessment of Donor Hearts in DCD Donors Using Thoracoabdominal Normothermic Regional Perfusion [Meeting Abstract]

Gidea, C. G.; James, L.; Smith, D.; Carillo, J.; Reyentovich, A.; Saraon, T.; Goldberg, R.; Kadosh, B.; Ngai, J.; Piper, G.; Moazami, N.
ISSN: 1053-2498
CID: 5243522

Interleukin-2 Receptor Antagonists Induction Therapy in Simultaneous Heart - Kidney Transplantation [Meeting Abstract]

Samra, A.; Gidea, C.; Malik, T.; Sikand, N.; Montgomery, R.; Lonze, B.; Reyentovich, A.; Saraon, T.; Soomro, I.; Goldberg, R.; Tatapudi, V.; Ali, N.; Moazami, N.; Mattoo, A.
ISSN: 1053-2498
CID: 5243532

Transplant Outcomes in Hearts with Moderate to Severe Left Ventricular Hypertrophy After the 2018 OPTN/UNOS Allocation Changes [Meeting Abstract]

Ramachandran, A.; Siddiqui, E.; Reyentovich, A.; Lonze, B.; Saraon, T.; Rao, S.; Katz, S.; Goldberg, R.; Kadosh, B.; DiVita, M.; Cruz, J.; Carillo, J.; Smith, D.; Moazami, N.; Gidea., C.
ISSN: 1053-2498
CID: 5243542

Defining the Normal Values for Left Ventricular Global Longitudinal Strain in Adult Heart Transplanted Patients [Meeting Abstract]

Sikand, N. V.; Maidman, S.; Saric, M.; Reyentovich, A.; Saraon, T.; Rao, S.; Katz, S.; Goldberg, R.; Kadosh, B.; DiVita, M.; Cruz, J.; Riggio, S.; Moazami, N.; Gidea, C.
ISSN: 1053-2498
CID: 5243562

Cardiogenic shock complicating multisystem inflammatory syndrome following COVID-19 infection: a case report

Gurin, Michael I; Lin, Yue J; Bernard, Samuel; Goldberg, Randal I; Narula, Navneet; Faillace, Robert T; Alviar, Carlos L; Bangalore, Sripal; Keller, Norma M
BACKGROUND:With the high prevalence of COVID-19 infections worldwide, the multisystem inflammatory syndrome in adults (MIS-A) is becoming an increasingly recognized entity. This syndrome presents in patients several weeks after infection with COVID-19 and is associated with thrombosis, elevated inflammatory markers, hemodynamic compromise and cardiac dysfunction. Treatment is often with steroids and intravenous immunoglobulin (IVIg). The pathologic basis of myocardial injury in MIS-A, however, is not well characterized. In our case report, we obtained endomyocardial biopsy that revealed a pattern of myocardial injury similar to that found in COVID-19 cardiac specimens. CASE PRESENTATION:A 26-year-old male presented with fevers, chills, headache, nausea, vomiting, and diarrhea 5 weeks after his COVID-19 infection. His SARS-CoV-2 PCR was negative and IgG was positive, consistent with prior infection. He was found to be in cardiogenic shock with biventricular failure, requiring inotropes and diuretics. Given concern for acute fulminant myocarditis, an endomyocardial biopsy (EMB) was performed, showing an inflammatory infiltrate consisting predominantly of interstitial macrophages with scant T lymphocytes. The histologic pattern was similar to that of cardiac specimens from COVID-19 patients, helping rule out myocarditis as the prevailing diagnosis. His case was complicated by persistent hypoxemia, and a computed tomography scan revealed pulmonary emboli. He received IVIg, steroids, and anticoagulation with rapid recovery of biventricular function. CONCLUSIONS:MIS-A should be considered as the diagnosis in patients presenting several weeks after COVID-19 infection with severe inflammation and multi-organ involvement. In our case, EMB facilitated identification of MIS-A and guided therapy. The patient's biventricular function recovered with IVIg and steroids.
PMID: 34715788
ISSN: 1471-2261
CID: 5042902

COVID-19 Impact on Heart Organ Transplantation - New Insights from a Single-Center Experience [Meeting Abstract]

Gidea, C G; Moazami, N; Neumann, H; Fargnoli, A; Pavone, J; Lewis, T; Saraon, T; Goldberg, R; Kadosh, B; Katz, S; Rao, S; Metha, S; Smith, D; Reyentovich, A
Purpose: During the COVID 19- pandemic, there is no consensus on management strategies for treating infected heart transplant patients. The outcomes of these patients vary by institution. We report our center experience and management strategies to date.
Method(s): All patients who received heart transplantation, from January 4th 2018 to September 25th 2020 and were diagnosed with SARS-CoV-2 were included and full chart review was performed.
Result(s): There were 113 heart transplants at our institution by September 2020. A total of 13 (12%) patients were infected with SARS-CoV-2: 9 (69%) isolated heart, 3 heart -kidney (23%) and 1 heat- lung (8%). The median (IQR) time from transplant to diagnosis was 10 (5-16) months. The mean age was 57 years and 50% were male; 50% were of Hispanic ethnicity. The main presenting symptoms were fever (43%), cough (86%) and SOB (43%). Chest x-ray was abnormal in all patients. We evaluated all patients and 79% were hospitalized and 21% were closely monitored as outpatients. None of our patients were hospitalized at outside institutions. Two (14%) required intubation and none required V-V ECMO support. The immunotherapy was modified in all patients: MMF and prednisone were discontinued, tacrolimus dose was reduced. COVID19 treatment was: 71% received hydroxychloroquine, 50% azithromycin, 15% remdesevir, 7% convalescent plasma. All hospitalized patients received anticoagulation. One patient had 2R/3A rejection within 30 days prior to diagnosis. Graft function was maintained in all patients with median LVEF% 65 (59-65%) except one patient who had received thymoglobulin 2 weeks prior to COVID 19 infection (LVEF 30%). The patient had a prolonged intubation but ultimately recovered and was discharged from the hospital. The one death (7.1%) was a heart - kidney recipient who concomitantly presented with pseudomonas sepsis and severe neutropenia. The remaining patients have all been discharged home.
Conclusion(s): We present our single center experience in managing COVID 19 infected heart transplant patients. We implemented uniform management strategies by incorporating aggressive reduction of immunosuppression, frequent scheduled contacts with infected outpatients and making sure all infected patients requiring hospitalization were treated at a transplant center.
ISSN: 1557-3117
CID: 5138672