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Missed Opportunities in Identifying Cardiomyopathy Aetiology Prior to Advanced Heart Failure Therapy

Aiad, Norman; Elnabawai, Youssef A; Li, Boyangzi; Narula, Navneet; Gidea, Claudia; Katz, Stuart D; Rao, Shaline D; Reyentovich, Alex; Saraon, Tajinderpal; Smith, Deane; Moazami, Nader; Pan, Stephen
BACKGROUND:Specific aetiologies of cardiomyopathy can significantly impact treatment options as well as appropriateness and prioritisation for advanced heart failure therapies such as ventricular assist device (VAD) or orthotopic heart transplantation (OHT). We reviewed the tissue diagnoses of patients who underwent advanced therapies for heart failure (HF) to identify diagnostic discrepancies. METHODS:This study presents a retrospective cohort of the aetiology of cardiomyopathy in 118 patients receiving either durable VAD or OHT. Discrepancies between the preoperative aetiological diagnosis of cardiomyopathy with the pathological diagnosis were recorded. Echocardiographic and haemodynamic data were reviewed to examine differences in patients with differing aetiological diagnoses. RESULTS:Twelve (12) of 118 (12/118) (10.2%) had a pathological diagnosis that was discordant with pre-surgical diagnosis. The most common missed diagnoses were infiltrative cardiomyopathy (5) and hypertrophic cardiomyopathy (3). Patients with misidentified aetiology of cardiomyopathy had smaller left ventricular (LV) dimensions on echocardiography than patients with dilated cardiomyopathy (5.8±0.9 vs 6.7±1.1 respectively p=0.01). CONCLUSIONS:Most HF patients undergoing VAD and OHT had a correct diagnosis for their heart failure prior to treatment, but a missed diagnosis at time of intervention (VAD or OHT) was not uncommon. Smaller LV dimension on echocardiogram in a patient with a non-ischaemic cardiomyopathy warrants further workup for a more specific aetiology.
PMID: 35165053
ISSN: 1444-2892
CID: 5163352

Use of Sodium-Glucose Cotransporter-2 Inhibitors in Clinical Practice for Heart Failure Prevention and Treatment: Beyond Type 2 Diabetes. A Narrative Review

Rao, Shaline
Despite the availability of established treatments, heart failure (HF) is associated with a poor prognosis and its management is suboptimal, highlighting the need for new options for treatment and prevention. Patients with type 2 diabetes (T2D) often experience cardiovascular (CV) complications, with HF being one of the most frequent. Consequently, several CV outcome trials have focused on glucose-lowering therapies and their impact on CV outcomes. An established treatment for T2D, sodium-glucose cotransporter-2 inhibitors (SGLT-2is; canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) have demonstrated beneficial effects on CV outcomes in long-term studies of patients with T2D with established CV disease and/or a broad range of CV risk factors. Recent studies have extended these findings to patients with HF, with and without T2D, finding that SGLT-2is (particularly dapagliflozin and empagliflozin) are effective therapeutic interventions for the treatment and prevention of HF. This narrative review article discusses the use of SGLT-2is in the treatment and prevention of HF in patients with and without T2D. Dapagliflozin was the first SGLT-2i to receive US Food and Drug Administration (FDA) approval for treatment of HF, to reduce the risk of CV death and hospitalization for HF in adults with HF with reduced ejection fraction (HFrEF) with and without T2D. Recently, the FDA also approved empagliflozin for this indication. Given the new HFrEF indications for dapagliflozin and empagliflozin, and the likelihood of similar approvals for other SGLT-2is, cardiology guidelines are beginning to integrate SGLT-2is into a standard-of-care treatment regimen for patients with HFrEF. The utility of SGLT-2is in HF with preserved EF (HFpEF) shows promise based on data from the EMPEROR-Preserved study of empagliflozin in patients with HFpEF. Further clinical trial evidence may lead to more widespread use and further integration of SGLT-2is into standard-of-care regimens for the treatment and management of HF in patients with and without T2D.
PMID: 34881413
ISSN: 1865-8652
CID: 5082902

Increased early acute cellular rejection events in hepatitis C-positive heart transplantation

Gidea, Claudia G; Narula, Navneet; Reyentovich, Alex; Fargnoli, Anthony; Smith, Deane; Pavone, Jennifer; Lewis, Tyler; Karpe, Hannah; Stachel, Maxine; Rao, Shaline; Moreira, Andre; Saraon, Tajinderpal; Raimann, Jochen; Kon, Zachary; Moazami, Nader
BACKGROUND:Increased utilization of hepatitis C virus (HCV)-positive donors has increased transplantation rates. However, high levels of viremia have been documented in recipients of viremic donors. There is a knowledge gap in how transient viremia may impact acute cellular rejections (ACRs). METHODS:In this study, 50 subjects received hearts from either viremic or non-viremic donors. The recipients of viremic donors were classified as nucleic acid amplification testing (NAT)+ group, and the remaining were classified as NAT-. All patients were monitored for viremia levels. Endomyocardial biopsies were performed through 180 days, evaluating the incidence of ACRs. RESULTS:A total of 50 HCV-naive recipients received hearts between 2018 and 2019. A total of 22 patients (44%) who received transplants from viremic donors developed viremia at a mean period of 7.2 ± 0.2 days. At that time, glecaprevir/pibrentasvir was initiated. In the viremia period (<56 days), 14 of 22 NAT+ recipients (64%) had ACR vs 5 of 28 NAT- group (18%) (p = 0.001). Through 180 days, 17 of 22 NAT+ recipients (77%) had a repeat rejection biopsy vs 12 of 28 NAT- recipients (43%) (p = 0.02). NAT+ biopsies demonstrated disparity of ACR distribution: negative, low-grade, and high-grade ACR in 84%, 12%, and 4%, respectively, vs 96%, 3%, and 1%, respectively, in the NAT- group (p = 0.03). The median time to first event was 26 (interquartile range [IQR]: 8-45) in the NAT+ group vs 65 (IQR: 44-84) days in the NAT-. Time to first event risk model revealed that NAT+ recipients had a significantly higher rate of ACR occurrences, adjusting for demographics (p = 0.004). CONCLUSIONS:Transient levels of viremia contributed to higher rates and severity of ACRs. Further investigation into the mechanisms of early immune activation in NAT+ recipients is required.
PMID: 32739334
ISSN: 1557-3117
CID: 4553482

Outcomes with Treatment with Glecaprevir/Pibrentasvir Following Heart Transplantation Utilizing Hepatitis C Viremic Donors

Reyentovich, Alex; Gidea, Claudia G; Smith, Deane; Lonze, Bonnie; Kon, Zachary; Fargnoli, Anthony; Pavone, Jennifer; Rao, Shaline; Saraon, Tajinderpal; Lewis, Tyler; Qian, Yingzhi; Jacobson, Ira; Moazami, Nader
BACKGROUND:The use of direct acting antivirals (DAA) has expanded transplantation from hepatitis C viremic donors (HCV-VIR). Our team has conducted an open-label, prospective trial to assess outcomes transplanting HCV-viremic hearts. Glecaprevir/Pibrentasvir (GLE/PIB) was our sole DAA. METHODS:Serial quantitative hepatitis C virus (HCV) RNA PCR was obtained to assess HCV viral titers. Between January 2018 to June 2019, a total of 50 recipients were transplanted. Of these, 22/50 (44%) were from HCV-VIR, the remaining 28 from non-viremic (HCV NON-VIR) donors. An 8 week course of GLE/PIB was initiated at 1 week post-transplant. RESULTS:There was no difference in demographic or clinical parameters between groups. All 22 recipients of HCV-VIR transplants became viremic. GLE/PIB was effective in decreasing viremia to undetectable levels by 6 weeks post-transplant in all patients. The median time to first undetectable HCV quantitative PCR was (4.3 weeks, IQR: 4-5.7 weeks). All patients demonstrated sustained undetectable viral load through 1 year follow up. There was no difference in survival at one year between HCV NON-VIR 28/28: (100%) vs. HCV-VIR 21/22 (95%) recipients. CONCLUSIONS:Our center reports excellent outcomes in transplanting utilizing hearts from HCV-VIR donors. No effect on survival or co-morbidity was found. An 8 week GLE/PIB course was safe and effective when initiated approximately 1 week post-transplant.
PMID: 32441413
ISSN: 1399-0012
CID: 4444732

The Use of Hemodynamics Does Not Aide in Correctly Identifying the Etiology of Cardiomyopathy in Patients Receiving Advanced Therapy [Meeting Abstract]

Aiad, Norman; Narula, Navneet; Gidea, Claudia G.; Katz, Stuart D.; Rao, Shaline; Reyentovich, Alex; Saraon, Tajinderpal S.; Smith, Deane; Moazami, Nader; Pan, Stephen
ISI:000607190400098
ISSN: 0009-7322
CID: 4916692

Missed Opportunities in Identifying Cardiomyopathy Etiology Prior to Advanced Heart Failure Therapy [Meeting Abstract]

Aiad, N; Li, B; Narula, N; Gidea, C; Katz, S; Rao, S D; Reyentovich, A; Saraon, T; Smith, D; Moazami, N; Pan, S
Purpose: In October 2018, a new US adult heart allocation scheme was enacted in which the etiology of cardiomyopathy can play a significant role in the prioritization of patients listed for transplantation. Given this, we embarked on a review of the diagnoses of patients who underwent therapy for advanced heart failure at our center.
Method(s): We retrospectively reviewed the etiology of cardiomyopathy of patients receiving either durable ventricular assist device (VAD) or orthotopic heart transplantation (OHT) at NYU Langone Medical Center in New York, NY between January 2011 and October 2018. We evaluated for discrepancies between the primary HF diagnosis at time of operation with the ultimate diagnosis, combining both clinical follow-up data and cardiac pathology.
Result(s): During the study period, a total of 110 patients were treated with advanced therapies, of which the majority (74.5%) were male. 40.9% were African American, 35.4% Caucasian, 4.5% Asian, and 23.6% Hispanic. 86.3% underwent VAD and 22.0% underwent OHT. The average age of those undergoing OHT and VAD were 58 and 61 respectively. The most common reported etiology of HF was dilated cardiomyopathy (57.3%), followed by ischemic (36.3%), familial DCM (1.8%), amyloidosis (1.8%), restrictive cardiomyopathy (1.8%), and sarcoidosis (0.9%). On final review of the diagnoses in these patients, 14 (12.7%) had a final diagnosis that was inconsistent with the prior reported one. 5 were clerical errors, but 9 were significant deviations from the prior diagnosis. The most common diagnoses that were misidentified prior to VAD or OHT were cardiac sarcoidosis (2), cardiac amyloidosis (2), and hypertrophic cardiomyopathy (2). Among those 9 patients, 7 patients received VAD with 5 eventually requiring OHT (median days to OHT = 248); 2 patients directly received OHT. All of those are alive except one patient who was lost to follow-up (transferred care to another center). Patients in whom the diagnosis was misidentified prior to VAD or OHT had smaller LV dimensions on transthoracic echocardiography on average than other LVAD or OHT patients with non-ischemic cardiomyopathy.
Conclusion(s): In this single-center review, we found that the majority of HF patients undergoing VAD and OHT had a correct diagnosis for their heart failure prior to treatment, although notably 8.1% had a missed diagnosis at time of intervention (VAD or OHT). Appropriately identifying the subtype of cardiomyopathy remains challenging especially in advanced HF patients but can significantly impact waiting list time in the current organ allocation scheme. A normal or minimally increased LV dimension on echocardiogram in a patient with advanced non-ischemic cardiomyopathy may warrant further workup for another diagnosis.
Copyright
EMBASE:2002535684
ISSN: 1532-8414
CID: 4043812

Clinical Experience with Heart Transplantation from Hepatitis C Positive Donors [Meeting Abstract]

Reyentovich, A.; Gidea, C.; Smith, D.; Lonze, B.; Pavone, J.; Katz, S.; Pan, S.; Rao, S.; Saraon, T.; Moazami, N.
ISI:000461365100095
ISSN: 1053-2498
CID: 3803772

Aortic Valve Opening Time, a Novel Parameter to Describe the Aortic Valve in Patients with Continuous Flow Devices [Meeting Abstract]

Mai, X.; Reyentovich, A.; Moazami, N.; Soria, C.; Smith, D.; Katz, S.; Pan, S.; Rao, S.; Saraon, T.; Gidea, C.
ISI:000461365103160
ISSN: 1053-2498
CID: 3803762

Magnitude of Recipient Viremia after Heart Transplantation from HCV Viremic Donors and Time to Clearance with Therapy [Meeting Abstract]

Gidea, C. G.; Reyentovich, A.; Smith, D.; Pavone, J.; Katz, S.; Pan, S.; Rao, S.; Saraon, T.; Moazami, N.
ISI:000461365100138
ISSN: 1053-2498
CID: 3803752

The Impact of HCV Viremia in Heart Transplant Recipients from Donors with HCV Infection on Acute and Humoral Cellular Rejection [Meeting Abstract]

Gidea, C. G.; Narula, N.; Reyentovich, A.; Smith, D.; Pavone, J.; Katz, S.; Pan, S.; Rao, S.; Saraon, T.; Moazami, N.
ISI:000461365100140
ISSN: 1053-2498
CID: 3803742