Heart transplant recipient 1-year outcomes during the COVID-19 pandemic.

The COVID-19 pandemic initially brought forth considerable challenges to the field of heart transplantation. To prevent the spread of the virus and protect immunocompromised recipients, our center made the following modifications to post-transplant outpatient management: eliminating early coronary angiograms, video visits for postoperative months 7, 9, and 11, and home blood draws for immunosuppression adjustments. To assess if these changes have impacted patient outcomes, the current study examines 1-year outcomes for patients transplanted during the pandemic. Between March and September 2020, we assessed 50 heart transplant patients transplanted during the pandemic. These patients were compared to patients who were transplanted during the same months between 2011 and 2019 (n = 482). Endpoints included subsequent 1-year survival, freedom from cardiac allograft vasculopathy, any-treated rejection, acute cellular rejection, antibody-mediated rejection, nonfatal major adverse cardiac events (NF-MACE), and hospital and ICU length of stay. Patients transplanted during the pandemic had similar 1-year endpoints compared to those of patients transplanted from years prior apart from 1-year freedom from NF-MACE which was significantly higher for patients transplanted during the pandemic. Despite necessary changes being made to outpatient management of heart transplant recipients, heart transplantation continues to be safe and effective with similar 1-year outcomes to years prior.

Risk of deep vein thrombosis and pulmonary embolism after heart transplantation: clinical outcomes comparing upper extremity deep vein thrombosis and lower extremity deep vein thrombosis.

INTRODUCTION: Heart transplant patients have risk factors that place them at higher risk for acute venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), than the general population. We assessed for rate of VTE and incidence of PE-related mortality among heart transplant patients. MATERIALS AND METHODS: A total of 1258 heart transplant patients were evaluated for the development of VTE. The diagnosis of DVT was made by Duplex ultrasonography, and PE was diagnosed by computerized tomography pulmonary angiography or ventilation-perfusion radionuclide scan. PE-related mortality was assessed at one yr, three yr, and five yr post-transplant. RESULTS: A total of 117 (9.3%) patients were diagnosed with DVT, including 65 of 117 (55.5%) with lower extremity DVT (LEDVT) and 52 of 117 (44.4%) with upper extremity DVT (UEDVT). A total of 24 (1.9%) patients experienced PE with seven (29.2%) resulting deaths. The rate of LEDVT and UEDVT was similar (55.5% vs. 44.4%); however, the incidence of PE was greater for those with LEDVT (23.1% vs. 7.7%; p = 0.04). Patients with PE had lower survival over the five-yr follow-up period compared to those with DVT only (67% vs. 81%; p = 0.51). CONCLUSION: Heart transplant patients have a high incidence of VTE despite current best practice, indicating a need for a more aggressive approach to thromboprophylaxis.

Clinical and angiographic outcomes with everolimus eluting stents for the treatment of cardiac allograft vasculopathy.

OBJECTIVES: This study aimed to examine clinical efficacy, safety, and intermediate clinical outcomes with everolimus-eluting stents (EESs) in patients with transplant coronary artery disease (TCAD). BACKGROUND: TCAD is a major cause of mortality in patients following orthotopic heart transplantation (OHT). Systemic everolimus in OHT patients has been shown to reduce TCAD. The safety and efficacy of an EES, the Xience V, have not been evaluated in this population. METHODS: Patients post-OHT with hemodynamically significant CAD who underwent percutaneous coronary intervention (PCI) with EES were included. Participants were maintained on dual antiplatelet therapy for 1-year post-PCI. We examined procedural success, in-hospital and 1-year mortality, stent thrombosis, angiographic restenosis, and myocardial infarction rates. All patients had follow-up angiography 1-year after PCI. Target vessel revascularization (TVR), target lesion revascularization (TLR), in-segment restenosis, target vessel failure (TVF), and lumen late loss were noted. RESULTS: PCI was performed in 34 de novo lesions in 21 patients, and 40 EES were placed. Procedural success rate was 100%. Average stent was 16.5 ± 5.1 mm long and 3.0 ± 0.6 mm in diameter. All patients had angiographic follow-up (409 ± 201 days). There was no stent thrombosis, deaths, or myocardial infarctions during follow-up. Two patients had focal in-stent restenosis. TLR rate was 5.9% (2/34), and TVR rate was 11.1% (3/27). Quantitative coronary angiography (QCA) showed stenosis diameter to be 19.98 ± 17.57%. CONCLUSIONS: Use of an EES is associated with a low incidence of TVR and TLR in patients with TCAD. Further studies are needed to determine whether PCI with EES changes long-term outcomes.

The policy of placing older donors into older recipients: is it worth the risk?

BACKGROUND: To expand the donor pool, older donors (≥50 yr) are frequently used in older recipients (≥60 yr). Older recipients and those receiving older donor hearts have independently displayed decreased post-transplant survival. However, outcomes in older patients receiving older donor hearts are contentious. METHODS: Eight hundred and seventy-nine heart transplant patients between 2000 and 2010 were analyzed, excluding patients with donor coronary artery disease. From 380 patients ≥60 yr, 327 patients with donors <50 yr old were compared with 53 patients with donors ≥50 yr old for: five-yr actuarial survival, freedom from cardiac allograft vasculopathy (CAV: stenosis ≥30%), non-fatal major adverse cardiac events (NF-MACE: MI, CHF, stroke, need for pacemaker/ICD), one-yr freedom from any treated rejection. RESULTS: The older vs. younger donor group demonstrated significantly lower five-yr survival (57% vs. 85%, p < 0.001) and freedom from CAV (83% vs. 92%, p = 0.03). No difference was observed in five-yr freedom from NF-MACE and one-yr freedom from any treated rejection. Multivariate analysis found donor age ≥50 to be an independent risk factor for death (HR 1.8, CI 1.1-2.9, p = 0.008) and CAV (HR 1.9, CI 1.2-2.9, p = 0.004). CONCLUSIONS: Use of older donors (≥50 yr) in older recipients (≥60 yr) results in lower five-yr survival and freedom from CAV. Caution is required in these cases. Larger studies are warranted to confirm findings.

The impact of mean first-year heart rate on outcomes after heart transplantation: does it make a difference?

BACKGROUND: Cardiac denervation following transplantation has a variable effect on heart rate (HR), and the consequence of this is not known. We examined the impact of first-year HR on five-yr outcomes after heart transplant. METHODS: We evaluated 544 heart transplant recipients from 1994 to 2008. Patients were divided into groups by mean first-year HR: group 1, HR < 90 (mean 85.0 ± 4.3); group 2, 90 ≤ HR < 110 (mean 97.8 ± 4.9); group 3, HR ≥ 110 (mean 111.5 ± 1.8). Endpoints included one-yr freedom from treated rejection, five-yr survival, five-yr freedom from cardiac allograft vasculopathy (CAV), and five-yr freedom from non-fatal major adverse cardiac events (NF-MACE). RESULTS: One-yr freedom from treated rejection, five-yr survival and freedom from CAV were not significantly different between groups. Five-yr freedom from NF-MACE was significantly lower in group 3 compared with group 2, 69% vs. 91%, p < 0.01, mainly due to higher prevalence of congestive heart failure (CHF) in group 3 over five yr. CONCLUSIONS: Mean first-year HR does not provide prognostic significance for one-yr freedom from treated rejection, five-yr survival or development of CAV five yr after heart transplant. These results suggest that HR post-heart transplantation does not affect long-term outcomes, but high first-year HRs may be associated with new-onset CHF.

Increased negative impact of donor HLA-specific together with non-HLA-specific antibodies on graft outcome.

BACKGROUND: De novo donor HLA-specific (dnDSA) and non-HLA antibodies including antiangiotensin type 1 receptor antibodies (AT1R-abs) have been associated with antibody-mediated rejection (AMR) and decreased graft survival as well as cellular-mediated rejection (CMR) and early onset of microvasculopathy in heart transplantation. The aim of our study was to determine the impact of anti-AT1R-ab and anti-donor HLA-specific antibody (DSA) on clinical outcomes. METHODS: Pretransplant and posttransplant sera from 200 recipients transplanted between May 2007 and August 2011 were tested for DSA (Luminex-based single antigen bead assay) and AT1R-ab (enzyme-linked immunosorbent assay). Two cutoff levels (≥ 17 and ≥ 12 units) were used to define high and intermediate binding of AT1R-ab. Clinical parameters examined were 5-year AMR/CMR (≥ grade 2), coronary artery vasculopathy, and survival. RESULTS: At 2 years after transplant, freedom from AMR and/or CMR was 95.4% for those with no DSA (n=175), 66.9% for those with dnDSA (n=19), and 25% for those with DSA at transplant (n=6) (P<0.0001). Neither ≥ 17 nor ≥ 12 units of pretransplant levels indicated a significant difference in freedom from AMR and/or CMR. When both dnDSA and AT1R-ab ≥ 17 or ≥ 12 units were considered, freedom from AMR and/or CMR decreased to 50% and 45% (P<0.0001), respectively. Coronary artery vasculopathy and survival were not significantly impacted. CONCLUSIONS: These results show the increased negative impact of dnDSA and AT1R-ab on freedom from AMR and/or CMR and an increased hazard ratio when both parameters are considered. Both HLA- and non-HLA-specific antibodies seem to impact graft outcome in heart transplantation.

The natural history of biopsy-negative rejection after heart transplantation.

Purpose. The most recent International Society for Heart and Lung Transplantation (ISHLT) biopsy scale classifies cellular and antibody-mediated rejections. However, there are cases with acute decline in left ventricular ejection fraction (LVEF ≤ 45%) but no evidence of rejection on biopsy. Characteristics and treatment response of this biopsy negative rejection (BNR) have yet to be elucidated. Methods. Between 2002 and 2012, we found 12 cases of BNR in 11 heart transplant patients as previously defined. One of the 11 patients was treated a second time for BNR. Characteristics and response to treatment were noted. Results. 12 cases (of 11 patients) were reviewed and 11 occurred during the first year after transplant. 8 cases without heart failure symptoms were treated with an oral corticosteroids bolus and taper or intravenous immunoglobulin. Four cases with heart failure symptoms were treated with thymoglobulin, intravenous immunoglobulin, and intravenous methylprednisolone followed by an oral corticosteroids bolus and taper. Overall, 7 cases resulted in return to normal left ventricular function within a mean of 14 ± 10 days from the initial biopsy. Conclusion. BNR includes cardiac dysfunction and can be a severe form of rejection. Characteristics of these cases of rejection are described with most cases responding to appropriate therapy.

Impact of virtual cross match on waiting times for heart transplantation.

BACKGROUND: Heart transplantation for sensitized patients has been a significant challenge. In this study, outcome of heart transplantation in sensitized patients with virtual cross match was compared with prospective cross match. METHODS: Prior to July 2007, prospective cross match was used and afterward, virtual cross match with Luminex (One Lambda, Inc, Canoga Park, CA) based antibody analysis was used for potential heart transplant recipients. Prospectively collected data for the 3 years before and after July 2007, in sensitized (panel reactive antibody greater than 10%) and nonsensitized heart transplant recipients were reviewed. RESULTS: One hundred sixty-eight patients met inclusion criteria for analysis (78 patients for prospective cross match and 90 patients for virtual cross match). Multiple parameters were compared for the prospective cross match and virtual cross match eras. Three-year survivals in nonsensitized patients were 84.6% and 77.2% and in sensitized patients were 76.9% and 77.4% (p = 0.49) for prospective cross match and virtual cross match eras, respectively. Freedom from 3A (2R) cellular rejection in nonsensitized patients was 96.9% and 95.3%, and in sensitized patients was 90.9% and 100% (p = 0.83). Freedom from antibody-mediated rejection in nonsensitized patients was 95.3% and 96.8%, and in sensitized patients was 90.9% and 90.5% (p = 0.65). Mean waiting time was 129 ± 246 days (mean ± SD) for the period before virtual cross match and 59 ± 78 days with virtual cross match (p = 0.018). Donor geographic area was similar for prospective and virtual cross match. CONCLUSIONS: In sensitized heart transplant candidates, virtual cross match may shorten waiting time to heart transplantation without increasing subsequent occurrence of cellular rejection, antibody mediated rejection, and mortality after heart transplantation.