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While cytomegalovirus (CMV) reactivation occurs in immunocompetent patients who are critically ill and has been associated with worse outcomes, very few cases of CMV reactivation have been reported following left ventricular assist device (LVAD) implantation. We aimed to evaluate the incidence and risk factors for CMV reactivation following LVAD implantation. Retrospective chart review of patients who had undergone LVAD implantation between July 2004 and December 2018 was performed. Cases with CMV reactivation post-LVAD were randomly matched (1:2) by sex, LVAD type, and implant year with controls utilizing SAS macros. Fisher's exact and paired sample t-tests were performed to evaluate for differences between categorical and continuous variables, respectively. Days to reactivation post-LVAD implantation were calculated in cases, and the corresponding times post-LVAD implantation were determined in control patients for variable comparisons. Survival analysis was performed using the Kaplan-Meier method. Of the 349 patients reviewed, 208 (59.6%) patients were seropositive for CMV before LVAD implantation. Of these 208 patients, eight (3.8%) had CMV reactivation following LVAD implantation. The median time to CMV reactivation following LVAD implantation was 21.5 days (range, 6-177). Six (75%) patients had CMV viremia, and the other two had colitis and pneumonia without viremia. In comparison to controls, patients with CMV had higher creatinine levels (p = 0.039) and higher RDW (p = 0.05) and were more likely to have received steroids within the previous week (p = 0.028) and to have concurrent bacterial infection (p = 0.001). CMV reactivation following LVAD implantation is more frequent than expected. Early testing, diagnosis, and treatment in at-risk patients (i.e., renal failure, steroid use, elevated RDW) might improve clinical outcomes., Competing Interests: The authors have no relevant conflicts of interest to disclose. The authors received no internal or external funding to conduct this study., (Copyright © ASAIO 2020.)

Gastrointestinal bleeding (GIB) is a common cause of morbidity among patients supported by left ventricular assist devices (LVADs). The aim of this study was to identify if pre-LVAD right ventricular (RV) dysfunction is associated with risk of GIB after LVAD implantation. Of 398 patients implanted with LVADs between July 2008 and July 2016, 130 (33%) developed GIB at a median of 2.6 months following LVAD implantation. Arteriovenous malformations (AVMs) were found in 42 (34%) GIB patients. Patients with GIB were older and more likely to have hypertension, diabetes, and ischemic cardiomyopathy. On pre-LVAD echocardiography, GIB patients had increased RV diastolic dimension (4.7 ± 0.8 vs. 4.4 ± 0.9 cm, p = 0.02), a higher rate of greater than mild tricuspid valve (TV) regurgitation (73 [60%] vs. 120 [47%], p = 0.006), and underwent TV repair more often (38 [30%] vs. 43 [16%], p = 0.0006) during LVAD implantation. After multivariable adjustment, preoperative greater than mild RV enlargement (hazard ratio [HR] 2.32, 95% CI 1.12-5.03; p = 0.03), TV regurgitation (HR 1.83, CI 1.02-3.44; p = 0.01), and TV repair (HR 3.76, confidence interval [CI] 1.02-4.44; p = 0.01) remained associated with risk of GIB. This finding was driven by the AVM-GIB subgroup. Preoperative RV enlargement and TV regurgitation are associated with post-LVAD AVM-related GIB., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

Background: Exercise performance remains limited in some patients after heart transplantation (HTx). The goal of this study was to assess for association between cardiopulmonary exercise test performance at 1 year after HTx and future development of cardiac allograft vasculopathy (CAV)., Methods: Overall 243 HTx recipients performed cardiopulmonary exercise testing at 1 year after HTx. During the median follow-up period of 31 (interquartile range 19;61) months, 76 (32%) patients were diagnosed with CAV (CAV group)., Results: The CAV group patients had lower exercise capacity (5.2 ± 1.9 versus 6.5 ± 2.2 metabolic equivalents; P = 0.001) and duration (9.6 ± 3.5 versus 11.4 ± 4.8 min; P = 0.008), lower peak oxygen consumption (VO2) (18.4 ± 5.4 versus 21.4 ± 6.1 mL/kg/min; P = 0.0005), lower normalized peak VO2 (63% ± 18% versus 71% ± 19%; P = 0.007), and higher minute ventilation (VE)/carbon dioxide production (VCO2) (34 ± 5 versus 32 ± 5, P = 0.04). On Cox proportional hazards regression analysis, normalized peak VO2 ≤60%, and VE/VCO2 ≥34 were associated with a high hazard for CAV (HR = 1.8 [95% CI 1.10-4.53, P = 0.03] and 2.5 [95% CI 1.01-8.81, P = 0.04], respectively). The subgroup of patients with both normalized peak VO2 ≤60% and VE/VCO2 ≥34 was at highest risk for development of CAV (HR = 5.2, 95% CI 2.27-15.17, P = 0.001)., Conclusions: Normalized peak VO2 ≤60% and VE/VCO2 ≥34 at 1 year after HTx are associated with the development of CAV.

Clinical Features: Giant cell myocarditis (GCM) is a rare and a rapidly progressive disorder with fatal outcomes such that patients often require heart transplantation. We present a case of recurrent GCM in a transplanted patient with a history of Crohn disease requiring a novel therapeutic approach., Therapeutic Challenge: After the orthotopic heart transplantation, GCM recurred on aggressive immunosuppression over the months, which included corticosteroids, basiliximab, tacrolimus, antithymocyte globulin, and rituximab. Although combination immunosuppressive therapy containing cyclosporine and 2-4 additional drugs including corticosteroids, azathioprine, mycophenolate mofetil, muromonab, gammaglobulin, or methotrexate have shown to prolong the transplant-free survival by keeping the disease under control, its role in preventing and treating recurrence posttransplantation is unclear., Solution: We added sirolimus, a macrolide antibiotic, with properties of T- and B-lymphocyte proliferation inhibition on the above immunosuppressive treatment postrecurrence of GCM. After sirolimus initiation and continuation, the patient has remained disease free.

Psychosocial factors have been show to impact survival and outcomes in a number of different diseases, including heart failure and patients receiving heart transplantation. With the increasing utilization of these devices, it is important to identify risk factors that could impact post-left ventricular assist device (LVAD) outcomes. This study was a single center, retrospective analysis of 238 patients who underwent implantation of a LVAD between July 27, 2004, and July 21, 2016, at The University of Nebraska Medical Center. Data collected include length of stay, number of readmission, alive status at 30 days, 180 days, and 1 year, as well as multiple psychosocial factors including history of drug abuse, history of alcohol abuse, history of noncompliance, history of anxiety, and history of depression, among others. Outcomes were calculated using univariate and multivariate analyses with SAS Version 9.4. None of the psychosocial factors assessed in this study showed statistical significance in predicting 30 day or 6 month mortality, but patients who smoked at the time of admission for LVAD implantation had higher mortality at 1 year (odds ratio 4.6, 95% confidence interval, 1.226-15.898, p = 0.011.) Patients with a diagnosis of depression had higher numbers of readmissions compared with those without depression (p = 0.048) with the number of readmissions further increased in patients with a diagnosis of both depression and anxiety (p = 0.0074). Psychosocial determinants do not appear to have a significant effect on mortality, but can result in increased risk of readmission if not adequately addressed before implantation and continually monitored postimplantation.

The aim of this study was to evaluate clinical outcomes after left ventricular assist device (LVAD) implantation in patients with severe pre-LVAD renal dysfunction (RD). The cohort of 165 consecutive patients implanted with HeartMate II LVADs was divided into two groups: 1) baseline glomerular filtration rate (bGFR) ≤ 40 ml/min/1.73 m (n = 30), and 2) GFR > 40 ml/min/1.73 m (n = 135). In both groups, GFR increased significantly at 1 month and then declined, remaining higher than the pre-LVAD level in the bGFR ≤ 40 group and returning back to the pre-LVAD level in the bGFR > 40 group by 1 year post-LVAD follow-up. Post-LVAD dialysis was used in 20% of the bGFR ≤ 40 patients and 7% of the bGFR > 40 patients (p = 0.02). By 3 months, 14% patients had GFR ≤ 40 ml/min/1.73 m. Grade ≥2 tricuspid regurgitation (TR) (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.23-10.28; p = 0.02) and model for end-stage liver disease-XI score ≥ 17 (OR, 4.2; 95% CI, 1.45-12.24; p = 0.01) were risk factors for severe RD at 3 months after LVAD implantation. Eight bGFR ≤ 40 patients underwent heart transplantation. Carefully selected patients with advanced heart dysfunction and bGFR ≤ 40 ml/min/1.73 m can improve kidney function with LVAD support and be able to bridge to isolated heart transplantation. Additional research is needed to refine patient selection for LVAD.

Background: Adverse events (AEs), such as intracranial hemorrhage, thromboembolic event, and progressive aortic insufficiency, create substantial morbidity and mortality during continuous flow left ventricular assist device support yet their relation to blood pressure control is underexplored., Methods and Results: A multicenter retrospective review of patients supported for at least 30 days and ≤18 months by a continuous flow left ventricular assist device from June 2006 to December 2013 was conducted. All outpatient Doppler blood pressure (DOPBP) recordings were averaged up to the time of intracranial hemorrhage, thromboembolic event, or progressive aortic insufficiency. DOPBP was analyzed as a categorical variable grouped as high (>90 mm Hg; n=40), intermediate (80-90 mm Hg; n=52), and controlled (<80 mm Hg; n=31). Cumulative survival free from an AE was calculated using Kaplan-Meier curves and Cox hazard ratios were derived. Patients in the high DOPBP group had worse baseline renal function, lower angiotensin-converting enzyme inhibitor or angiotensin receptor blocker usage during continuous flow left ventricular assist device support, and a more prevalent history of hypertension. Twelve (30%) patients in the high DOPBP group had an AE, in comparison with 7 (13%) patients in the intermediate DOPBP group and only 1 (3%) in the controlled DOPBP group. The likelihood of an AE increased in patients with a high DOPBP (adjusted hazard ratios [95% confidence interval], 16.4 [1.8-147.3]; P=0.012 versus controlled and 2.6 [0.93-7.4]; P=0.068 versus intermediate). Overall, a similar association was noted for the risk of intracranial hemorrhage (P=0.015) and progressive aortic insufficiency (P=0.078) but not for thromboembolic event (P=0.638). Patients with an AE had a higher DOPBP (90±10 mm Hg) in comparison with those without an AE (85±10 mm Hg; P=0.05)., Conclusions: In a population at risk, higher DOPBP during continuous flow left ventricular assist device support was significantly associated with a composite of AEs., (© 2015 American Heart Association, Inc.)

Background: When β-blockers produce reverse-remodeling in idiopathic dilated cardiomyopathy, they partially reverse changes in fetal-adult/contractile protein, natriuretic peptide, SR-Ca(2+)-ATPase gene program constituents. The objective of the current study was to further test the hypothesis that reverse-remodeling is associated with favorable changes in myocardial gene expression by measuring additional contractile, signaling, and metabolic genes that exhibit a fetal/adult expression predominance, are thyroid hormone-responsive, and are regulated by β1-adrenergic receptor signaling. A secondary objective was to identify which of these putative regulatory networks is most closely associated with observed changes., Methods and Results: Forty-seven patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction, 0.24±0.09) were randomized to the adrenergic-receptor blockers metoprolol (β1-selective), metoprolol+doxazosin (β1/α1), or carvedilol (β1/β2/α1). Serial radionuclide ventriculography and endomyocardial biopsies were performed at baseline, 3, and 12 months. Expression of 50 mRNA gene products was measured by quantitative polymerase chain reaction. Thirty-one patients achieved left ventricular ejection fraction reverse-remodeling response defined as improvement by ≥0.08 at 12 months or by ≥0.05 at 3 months (Δ left ventricular ejection fraction, 0.21±0.10). Changes in gene expression in responders versus nonresponders were decreases in NPPA and NPPB and increases in MYH6, ATP2A2, PLN, RYR2, ADRA1A, ADRB1, MYL3, PDFKM, PDHX, and CPT1B. All except PDHX involved increase in adult or decrease in fetal cardiac genes, but 100% were concordant with changes predicted by inhibition of β1-adrenergic signaling., Conclusions: In addition to known gene expression changes, additional calcium-handling, sarcomeric, adrenergic signaling, and metabolic genes were associated with reverse-remodeling. The pattern suggests a fetal-adult paradigm but may be because of reversal of gene expression controlled by a β1-adrenergic receptor gene network., Clinical Trial Registration: URL: www.clinicaltrials.gov. Unique Identifier: NCT01798992., (© 2015 American Heart Association, Inc.)