Faculty Bibliography

PURPOSE: Thoracic organ transplantation from Hepatitis C (HCV) viremic donors is a promising strategy due to curative therapies for HCV. Currently, there is no consensus on the best time to initiate HCV therapy relative to time of transplantation. We assessed the difference in magnitude of viremia and time to clearance in recipients of heart (HT) and lung (LT) transplant, based on timing of starting antiviral HCV therapy.
METHOD(S): From January 2018 to October 2019, 42 patients received thoracic organs from viremic donors. All recipients were treated with Mavyret (glecaprevir/pibrentasvir) for 8 weeks. HT recipients received therapy at the time of detectable viremia, while LT recipients were preemptively treated within 3 days post-transplant. HCV viral load was monitored by RT-PCR.
RESULT(S): 23 patients received HT (mean age 59 +/- 9 years) and 19 patients received LT (mean age 60 +/- 9 years). HCV serologic testing was performed in HT recipients at a mean of 7 +/- 1 days and in LT recipients at a mean of 4 +/- 3 days post-transplant. At the time of testing, all HT and 14 LT patients had detectable viremia. Five LT patients never developed viremia. The mean viral load f HT was 4.5 logIU/mL and for LT was 1.6 logIU/ml. Viremia clearance was obtained at a mean of 28 +/- 13 days in HT and 21+/-11 days in LT recipients (p=0.13) (Fig). The mean time to HCV antibody (AB) clearance was 130 +/- 145 days in HT and 225 +/- 103 days in LT recipients (p=0.058). There was no correlation between the 2 groups in either the duration of viremia or HCV AB clearance.
CONCLUSION(S): Our study suggests that the magnitude and conversion to detectable viremia depends on the time of initiation of HCV therapy relative to time of transplant with complete conversion to HCV viremia in the HT group. Interestingly, there was no significance in time to viremia or HCV AB clearance between the two groups. This may be an organ specific response, but larger sample size studies need to be conducted to define the optimal time of starting HCV therapy.
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PURPOSE: Passive transmission of hepatitis C (HCV) viremia from actively infected donors to uninfected recipients at the time of heart transplantation may modulate response to alloantigens and risk of allograft rejection. We evaluated the one-year incidence of acute cellular rejection (ACR) in patients transplanted from nucleic amplification testing positive (NAT+) HCV donors compared to those from NAT negative (NAT-) donors.
METHOD(S): Since January 2018, 25 patients completed one-year follow-up. All recipients underwent right ventricular endomyocardial biopsy (EMB) per our institution protocol. ACR was graded according to both the 1990 and the revised 2004 International Society for Heart and Lung Transplantation (ISHLT) criteria. All NAT+ donor recipients developed viremia detected by RT-PCR. Mixed models were used to assess the association between donor HCV NAT status, recipient viremia, tacrolimus levels and ACR in the first year post-transplant.
RESULT(S): Twelve NAT+ recipients (mean age 60, 67% male) and 13 NAT- recipients (mean age 54, 77% male) completed one-year follow-up; 182 and 191 EMB were performed, respectively. NAT+ recipients were associated with higher grade rejection compared with NAT- recipients (p=0.041). At least one episode of high grade rejection (2R/3A) occurred in 4 NAT+ recipients (33%) compared with 2 NAT- recipients (15%). At least one episode of low grade rejection (1R/1B or 1R/2) occurred in 11 NAT+ recipients (92%) compared with 7 NAT- recipients (54%). These findings were independent of the presence and magnitude of viremia and tacrolimus levels. No episodes of ACR 3R or antibody mediated rejection were detected during one-year follow-up in either group. There was no allograft dysfunction or mortality related to ACR in either group.
CONCLUSION(S): One year data from our institution demonstrate increased ACR in heart transplant recipients from NAT+ donors. Most of the rejection episodes in the NAT+ group were low grade and did not translate into any adverse outcomes through one-year follow-up.
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Mechanical blood-immersed bearings have been used in many continuous-flow rotary blood pumps to reduce friction between relatively moving parts, but their use has been associated with a significant incidence of pump thrombosis. As newer cardiac assist devices with more advanced bearings become available, the rate of pump thrombosis will likely decrease. Nevertheless, it is important to understand the design limitations of mechanical bearings as pumps utilizing them are still in use as chronic support devices and especially in the acute setting for temporary support devices. A properly designed journal bearing should support the spinning rotor with no surface-to-surface contact between the bearing and journal surfaces. The journal continuously undergoes orbital motion within the bearing, which can be "stable" or "unstable." Unstable orbital motion causes the journal to move progressively off-center until it collides with the bearing, and even minor variations in manufacturing can create off-design operation and dynamic instability of the journal. Since blood is the lubricant in most clinically-used rotary blood pumps, lubricant viscosity can vary abruptly in response to changes in hematocrit or plasma protein concentration. Additionally, shear stress from the high-speed rotor can cause hemolysis and plasma protein denaturation. We reviewed theoretical design and operating principles of mechanical bearings and discuss why the phenomenon of mechanical bearing thrombosis may be an inherent design issue dependent on variables that are beyond the control of clinicians.

Purpose: Intra-aortic balloon pumps (IABPs) can be used to provide hemodynamic support in patients with end-stage heart failure. IABPs are commonly inserted via the femoral artery, which can limit patients' mobility. The Ramsey Protocol, developed by a critical care Physical Therapist (PT), allows patients with femoral IABPs to safely transfer out of bed to a standing position using a tilt table. Our institution adapted this protocol to create a clinical practice guideline for ambulating patients with femoral IABPs.
Method(s): Our team's guideline included key components of the Ramsey Protocol, such as assessment of the patient's pre-morbid function, strength, and medical stability, as well as monitoring of IABP augmentation, IABP waveforms pre- and post-mobilization, and tilt table follow during ambulation. Appropriate candidates were patients with stable hemodynamics who were ambulatory prior to IABP placement, demonstrated against gravity muscle strength, and followed multi-step instructions.
Result(s): From April 1, 2019 to August 31, 2019, 9 patients (mean age 57 +/- 15 years) underwent IABP insertion via either right or left femoral artery, as a bridge to transplant, and were mobilized following our protocol for a total of 27 ambulation sessions (Table). There were no adverse events associated with ambulation, defined as changes in IABP augmentation, waveform, and positioning, or bleeding requiring transfusion. The mean time from IABP to ambulation was 2 +/- 2 days. All patients were successfully transplanted with mean time of IABP support of 6 +/- 3 days and all were alive at 30 days post-transplant. There were no complications during IABP support (i.e. limb ischemia, hemorrhage, stroke, device dislodgement or failure, end-organ dysfunction, or balloon rupture).
Conclusion(s): Early mobilization in select patients with femoral IABPs can be performed safely and successfully, avoiding the deleterious effects of bedrest that have been historically seen in this patient population.
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Donation After Circulatory Death (DCD) is an alternative to Donation after Brain Death (DBD), and is a growing strategy for organ procurement in the United States (US). The purpose of this analysis was to review the number and quality of hearts in one United Network for Organ Sharing (UNOS) Region that were not utilized as a potential consequence of non-heart DCD donation. We retrospectively identified all successful US DCD solid organ donors from 1/2011 - 3/1/2017, defined an ideal heart donor by age and left ventricular ejection fraction, and then reviewed the donor charts of unused hearts in New York and Vermont (UNOS Region 9). Of 8302 successful DCD donors across the US, 5033 (61%) were between 18-49 years of age, 872 had a screening echocardiogram, with 573 (66%) measuring an EF > 50%. Of these 573 potential donors, 44 (7.7%) were from Region 9. Detailed donor chart review identified 36 ideal heart donors, 24 (66.7%) with anoxic brain injury. Trends in Region 9 DCD donation increased from 4 unused hearts in 2011, to 13 in 2016. In the context of severe organ scarcity, these data indicated that implementation of DCD heart transplantation in the US would improve overall donation rates and in particular, allow utilization of these ideal donor hearts.

BACKGROUND:The national opioid epidemic has expanded the donor pool for heart transplantation, but concerns remain regarding infectious risk and allograft function. This study compared donor and recipient characteristics, outcomes, and reasons for organ discard between overdose-death donors (ODDs) and donors with all other mechanism of death. METHODS:Data on adult cardiac transplants from 2010 to 2017 were provided by the Scientific Registry of Transplant Recipients. Cardiac allografts used in multiple organ transplantations were excluded. Recipient and donor characteristics and organ discard were analyzed with regard to ODDs. Kaplan-Meier curves and log-rank tests described mortality survival. RESULTS:A total of 1,710 of 15,904 (10.8%) cardiac transplantations were from ODDs, approximately a 10-fold increase from 2000 (1.2%). ODDs were more frequently older than 40 years of age (87.2% vs 70.1%; p < 0.001), had higher rates of substance abuse, were more likely hepatitis C positive (1.3% vs 0.2%; p < 0.001), and less frequently required inotropic support at the time of procurement (38.4% vs 44.8%; p < 0.001). Overall survival was not different between the groups (p = 0.066). Discarded ODD allografts were more likely to be hepatitis C positive (30.8% vs 5.3%; p < 0.001) and to be identified as conveying increased risk by the Public Health Services (63.3% vs 13.2%; p < 0.001), but they were less likely to be discarded because of a diseased organ state (28.2% vs 36.1%; p < 0.001). CONCLUSIONS:Rates of ODDs have increased corresponding with the worsening opioid epidemic. Even though ODDs have higher rates of hepatitis C, cardiac allograft quality indices are favorable, and recipient outcomes are similar when compared with non-ODDs, a finding indicating that greater use of this donor pool may be appropriate.

Amyloidosis describes a family of related disease states associated with the extracellular tissue deposition of fibrils composed of low-molecular-weight subunits of a variety of proteins circulating as constituents of plasma. Depending on the disease subtype, fibrillar deposits in a several organs including the heart, kidney, liver, and peripheral nerves cause organ dysfunction and associated morbidity and mortality. The most common amyloid fibril deposits associated with cardiac manifestations are of monoclonal light-chain or transthyretin (ATTR) types. This review will focus on the ATTR types of cardiac amyloidosis. ATTR amyloidosis may be associated with abnormal metabolism of wild-type transthyretin (previously called senile systemic amyloidosis) or with hereditary variants in the transthyretin gene. Cardiac amyloidosis is often under-recognized in its early stages, and when a diagnosis of cardiac amyloidosis is made, patients are often at the advanced stages of the disease. Treatments now available appear to exert their benefit predominantly in individuals with the early stages of disease. Increased awareness and early diagnosis of cardiac amyloidosis and continued discovery of effective therapies will increase opportunities to improve clinical outcomes in this patient population.

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.
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