Faculty Bibliography

BACKGROUND:The Impella (Abiomed) ventricular support system is a family of temporary mechanical circulatory support (MCS) devices used to treat patients with cardiogenic shock, acute cardiogenic decompensation, and for high-risk percutaneous or surgical revascularization. These devices include the percutaneously implanted 2.5/cardiac power (CP) and the surgically implanted 5.0/left direct (LD). Despite the beneficial effects and increased usage of these devices, data to assess adverse outcomes and guide clinician decision-making between the Impella CP and 5.0/LD are limited. METHODS:This is a retrospective analysis of 91 consecutive patients who required at least 24 h of Impella support, from January 1, 2015 to December 31, 2019. Groups were stratified based on either initial Impella CP or 5.0/LD placement. Clinical outcomes and in-hospital complications were compared. RESULTS:Impella CP was implanted in 66 patients (mean age: 61 ± 15 years, male 71.2%) and Impella 5.0/LD was implanted in 25 patients (mean age: 62 ± 9 years, male 84.0%). There was greater stability of device position (p = .033), less incidence of hemolysis (p < .001), and less frequent need for additional MCS (p = .001) in patients implanted with the Impella 5.0/LD compared with Impella CP in this study cohort. Patients with Impella 5.0/LD were more likely to survive from Impella and survive to discharge. CONCLUSIONS:This study suggests that for patients who require temporary MCS for more than 24 h, the Impella 5.0/LD may have a more favorable device-specific adverse profile compared with the Impella CP.

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: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.

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.

Study: Despite advances in design and hemocompatibility, pump thrombosis remains a significant cause of morbidity for patients implanted with durable left ventricular assist devices (LVAD). Pharmacologic fibrinolysis may be preferred as initial therapy because it obviates a surgical procedure. Yet, it historically has been associated with a significant risk of secondary intracerebral hemorrhage (ICH).
Method(s): We implemented a novel protocol to treat HVAD pump thrombosis and minimize risk of ICH that consisted of the following: initiation of a non-titrating heparin infusion at 500 units/hr; normalization of international normalized ratio (INR) by giving a flat dose of 1,000 units of four-factor prothrombin complex concentration (4F-PCC); and administration of alteplase as a 10 mg bolus followed by 40 mg given over 3 hours.
Result(s): Two patients underwent treatment with the above protocol for presumed HVAD pump thrombosis based on clinical signs of hemolysis and elevations of power on log-file analysis. One patient was 2 months from HVAD implant and the other 13 months. Both patients had subtherapeutic INR in the preceding weeks. Following administration of alteplase, log-file analysis demonstrated immediate resolution of power elevations (Fig. 1). Both patients had a subsequent rise in power requiring repeat alteplase dosing. No bleeding or thrombotic events occurred with treatment. One patient underwent heart transplant a month after treatment and is doing well; the second patient is stable on HVAD support 4 months following alteplase. Combining 4F-PCC to temporarily normalize the INR with repeat dosing of alteplase was effective at resolving HVAD pump thrombosis without bleeding complications and should be investigated further

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: 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.
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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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