Faculty Bibliography

We conducted a retrospective review of thoracic transplant recipients (22 heart and 16 lung transplant recipients) prospectively enrolled in a single-center observational study of HCV NAT+ organ transplantation in HCV NAT- recipients. All recipients were treated with 8 weeks of glecaprevir-pibrentasvir (GP) for HCV viremia in addition to standard triple immunosuppression post-transplant. Thoracic transplant recipients of HCV NAT- organs were used as a control (24 heart and 22 lung transplant recipients). Our primary outcome was to assess the effect of GP on tacrolimus dose requirements. Secondary objectives included assessing drug interactions with common post-transplant medications, adverse effects, and the need to hold or discontinue GP therapy. The median tacrolimus concentration-to-dose (CDR) in the cohort was 184 (99-260) during GP therapy and 154 (78-304) over the first month after GP (p=0.79). Trends in median tacrolimus CDR were similar on a per-week basis and per-patient basis. In three instances, concomitant posaconazole and GP led to hyperbilirubinemia and interruption of posaconazole. GP therapy was held in one heart transplant recipient, and discontinued in another, due to unresolving hyperbilirubinemia. Utilization of GP to treat HCV viremia post-thoracic transplant is feasible and safe, but requires modifications to post-transplant pharmacotherapy and careful monitoring for adverse effects.

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.
Copyright

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.
Copyright

PURPOSE: Heart transplantation from Hepatitis C (HCV) viremic donors is becoming increasingly used due to advent of direct acting antiviral drugs with almost 100% cure. There are limited data about its impact on cardiac allograft vasculopathy (CAV). We report the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic amplification test positive; NAT+) compared to non-HCV infected donors (NAT-).
METHOD(S): We retrospectively reviewed coronary angiograms with intravascular ultrasound (IVUS) of heart transplant recipients at our institution from January 5, 2018 to September 17, 2019. The presence of CAV was graded according to ISHLT guidelines. IVUS was performed as per our lab protocol on the left main and left anterior descending arteries. Maximal intimal thickness (MIT) was measured with advanced quantification software as per protocol. MIT >= 5mm was considered significant for future adverse outcomes.
RESULT(S): LHC and IVUS was performed on 24 heart transplant recipients (mean age 56; 70% male) at 1- year post transplant. Eleven of these patients were transplanted from NAT+ donors. Thirteen patients received a NAT- donor heart. Two recipients (18.7%) of NAT+ donors had CAV grade >= 1 compared to 2 (16.7%) from NAT- donors (p=1). MIT >= 5mm was seen in 88.9% of NAT+ vs 50% of NAT- recipients (p=0.14) (Figure). The mean MIT was 76mm and 65mm for NAT+ and NAT- group, respectively. Both NAT+ and NAT- donor recipients exhibit mostly eccentric (84.2%) and few (15.7%) demonstrated concentric plaques. There was no heterogeneity in the data after adjusting for risk factors for CAD and donor LHC.
CONCLUSION(S): Our data show no difference in the presence of (CAV >= grade 1) or subclinical atherosclerosis at 1 year among NAT+ donor recipients. HCV viremia is a known risk factor for accelerated atherosclerosis and the consequence of prolonged donor viremia on the recipient is not known. A larger cohort and further longitudinal follow-up is needed to assess the validity of this trend and its prognostic implications.
Copyright

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.

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.
Copyright

BACKGROUND:Despite innovations in left ventricular assist devices (LVAD) technology, stroke remains a leading cause of morbidity and mortality in this population. Major clinical trials of LVAD have used various definitions and approaches to measuring stroke outcomes which may limit comparison of stroke risk between different devices. METHODS:Data from the five major LVAD randomized, controlled, trials was abstracted to compare definitions of stroke (composite, ischemic, hemorrhagic and disabling) and stroke event rates across trials. Methodological limitations and suggestions to improve research and clinical practices for stroke and LVAD were identified. RESULTS:Comparison of stroke events across LVAD clinical trials is confounded by methodological variability including heterogeneity in stroke definitions, non-standardized evaluation of stroke etiology, oversimplification of stroke severity classification, and inconsistent event rate reporting due to data censoring at the time of death or transplant. Variability in the study of stroke in LVAD patients limits the ability to compare devices and design prevention strategies to mitigate stroke risk. CONCLUSIONS:Based on this review, we propose that future clinical trials: 1) utilize standardized stroke definitions and define stroke subtypes, 2) ensure that neurologists are integrated in study design and event adjudication, 3) include more thorough evaluations of stroke etiology using multimodality techniques, and 4) adopt the National Institutes of Health Stroke Scale to define stroke severity.

Background Arrhythmogenic cardiomyopathy (ACM) can mimic inflammatory processes. We present a complex patient with scleroderma (Sc)-dermatomyositis overlap syndrome (Sc-DM) and cardiac disease. Case A 57-year-old woman with family history of Sc presented with progressive weakness, dyspnea, edema, and Raynaud's (1A). Troponin was 1.6 ng/mL and CRP was 13.2 mg/L. EKGs revealed sinus rhythm with RBBB and AV sequential pacing with multifocal PVCs (1B-C). CT chest showed bibasilar fibrosis (1D). Echocardiography revealed biventricular dysfunction. Cardiac catheterization showed non-obstructive coronaries and a cardiac index of 1.8 L/min/m2. Cardiac MRI had diffuse biventricular subendocardial late gadolinium enhancement (1E). Electromyography revealed proximal myopathy. Rheumatologic workup was consistent with seronegative Sc-DM. Decision-making She was treated with steroids, mycophenolate, IV immunoglobulins, diuretics, and inotropes. Her course was complicated by recurrent VT cardiac arrests, prompting escalation to VA-ECMO. She underwent cardiac transplant on day 9 of ECMO. Pathology revealed biventricular fibrofatty replacement consistent with ACM (1F-G), patchy fibrosis of the pericardium, and mitral valve with thickened and fused chordae suggestive of inflammatory changes from Sc (1H-I). Conclusion This case highlights an atypical presentation of ACM in a patient with Sc-DM and the multidisciplinary approach necessary for proper diagnosis and management. [Figure presented]
Copyright