Steidley, D. Eric

Abstract Background Heart transplant (HTx) patients can develop graft dysfunction (GD) without biopsy evidence of cell or antibody mediated rejection. Cardiac MRI (CMR) can detect inflammatory or infiltrative causes of cardiomyopathy however CMR findings in HTx recipients with GD have not been previously described. Purpose We sought to identify CMR characteristics of HTx patients with GD, and evaluate its additive value in its diagnosis and prognosis. Methods CMR has been performed routinely to evaluate GD at our institutions. There were 37 HTx recipients who presented with acute decline in left ventricular ejection fraction (LVEF) of <50% and >10% from baseline, with no biopsy evidence of rejection between 2007 and 2018. Coronary angiogram with IVUS was done to rule out allograft vasculopathy. Treatment of GD was per discretion of the treating clinician. Responders were defined as those with LVEF improvement >10% at 180 days or greater post-presentation. LV and RV indices, the presence and pattern of late gadolinium enhancement (LGE) were determined by CMR. Results There were 34% females and mean age at transplant was 49±13 years. Median time from HTx to GD was 1.2 years. Presenting symptoms were heart failure (n=25), cardiogenic shock (n=1) and 11 patients were asymptomatic. Mean LVEF at presentation was 37±12% and donor specific antibodies were detected in 38% patients. Most patients were treated with steroid bolus (n=29), and/or plasmapheresis (n=23). There were no major changes made in immunosuppression in 6 patients. Delayed enhancement MRI was performed with standard inversion-recovery (IR) gradient echo sequences, between 5 and 20 minutes after institutional-standard protocol administration of IV gadolinium contrast. Biventricular LGE was present in 18/37 (49%) patients with GD and was more prevalent in responders (57%, 13 of 23) than non-responders (35%, 5 of 14), although not statistically significant (p=0.21). There were two patterns of LGE noted: 1) Diffuse epicardial (10 patients out which 9 were responders) and 2) Patchy pattern with non-specific distribution (8 patients out of which 4 were responders). Myocardial edema by triple IR sequencing was seen in 6 patients, all having diffuse epicardial pattern of enhancement matching the delayed enhancement pattern. When comparing different treatment groups, among those treated for GD (n=31), 12 of 21 (57%) responders had LGE and 4 of 10 (40%) non-responders had LGE (p=0.37), a pattern similar to the broader population. Among those not treated for GD (n=6), 1 of 2 responders had LGE and 1 of 4 non-responders had LGE (p=0.5). Conclusion CMR identified inflammation as a potential cause of GD in approximately 50% of HTx patients. There are 2 distinct patterns of LGE observed in GD, diffuse epicardial (56%) and patchy (44%). Although the presence of LGE in itself is not associated with myocardial recovery, 90% of patients with a diffuse epicardial pattern have recovery of GD. Funding Acknowledgement Type of funding source: None

Abstract Tricuspid valve regurgitation in orthotopic heart transplant recipients is common. Surgical corrections have been the mainstay of the treatment for diuretic-refractory heart failure due to severe tricuspid regurgitation. However, post-transplant patients inherently carry higher surgical risk owing to previous sternotomy and immunocompromised state. We report a case of successful percutaneous edge-to-edge tricuspid valve repair for severe tricuspid regurgitation after cardiac transplantation. A 27-year-old man with a history of idiopathic restrictive cardiomyopathy status after orthotopic heart transplant presented with severe right-sided heart failure symptoms. A transthoracic echocardiogram showed bi-atrial enlargement and moderate-to-severe tricuspid regurgitation, and an increase to the severe range with exercise. Percutaneous edge-to-edge tricuspid valve repair was performed. The patient's symptoms improved, and follow-up echocardiogram showed mild tricuspid regurgitation. Percutaneous tricuspid valve repair can be considered as an alternative option to conventional surgery for symptomatic severe tricuspid regurgitation in orthotopic heart transplant recipients with suitable anatomy.

Objectives: To report long-term outcomes of nonmelanoma skin cancer (NMSC) in immunosuppressed cardiac and liver transplant recipients (CLTR). Materials and Methods: The authors reviewed CLTR at the Mayo Clinic in Arizona from 1986 to 2013. Patient and tumor characteristics were recorded. Survival rates were calculated using the Kaplan-Meier method. Patient-specific and lesion-specific analyses were performed. Univariate and multivariate cox regressions were performed for comparisons. Results: Seven-hundred and forty-seven patients underwent cardiac (138) or liver (609) transplantation and of these, 97 patients (13%) developed 382 invasive NMSC. The median follow-up was 11 (range, 3 to 27) years for surviving patients. Primary treatment was mainly surgery alone. At 10 years, the local recurrence (LR) rate was 20% (95% confidence interval, 15%-28%), and 14% of patients had multiple LRs. At 10 years, LR rates were higher for T3/T4 tumors when compared with T1/T2 tumors (32.5% vs. 20%, P=0.05). At 10 years, overall survival was 79% (95% confidence interval, 64%-88%). On multivariate analysis, age 61 years and more demonstrated inferior overall survival (P<0.01). Conclusions: This is the first study describing the AJCC 8th edition stage-based patterns of recurrence and long-term outcomes of surgically managed NMSC in a large cohort of immunosuppressed CLTRs. T3 and T4 tumors recur more often than early stage tumors. Further study is required to identify factors related to recurrence and guide upfront treatment intensification in this high-risk population.

Background Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO 2peak ), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing. Methods and Results We outlined a pre–renal transplant screening algorithm to incorporate VO 2peak testing among a population of asymptomatic high‐risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO 2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO 2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all‐cause mortality. We report a high (>90%) negative predictive value, indicating that VO 2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all‐cause mortality. However, lower VO 2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant. Conclusions We conclude that incorporating an objective measure of cardiorespiratory fitness with VO 2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher‐risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.

Cardiovascular disease (CVD) is a leading cause of post–liver transplant death, and variable care patterns may affect outcomes. We aimed to describe epidemiology and outcomes of inpatient CVD care across US hospitals. Using a merged data set from the 2002‐2011 Nationwide Inpatient Sample and the American Hospital Association Annual Survey, we evaluated liver transplant patients admitted primarily with myocardial infarction (MI), stroke (cerebrovascular accident [CVA]), congestive heart failure (CHF), dysrhythmias, cardiac arrest (CA), or malignant hypertension. Patient‐level data include demographics, Charlson comorbidity index, and CVD diagnoses. Facility‐level variables included ownership status, payer‐mix, hospital resources, teaching status, and physician/nursing‐to‐bed ratios. We used generalized estimating equations to evaluate patient‐ and hospital‐level factors associated with mortality. There were 4763 hospitalizations that occurred in 153 facilities (transplant hospitals, n = 80). CVD hospitalizations increased overall by 115% over the decade (P < 0.01). CVA and MI declined over time (both P < 0.05), but CHF and dysrhythmia grew significantly (both P < 0.03); a total of 19% of hospitalizations were for multiple CVD diagnoses. Transplant hospitals had lower comorbidity patients (P < 0.001) and greater resource intensity including presence of cardiac intensive care unit, interventional radiology, operating rooms, teaching status, and nursing density (all P < 0.01). Transplant and nontransplant hospitals had similar unadjusted mortality (overall, 3.9%, P = 0.55; by diagnosis, all P > 0.07). Transplant hospitals had significantly longer overall length of stay, higher total costs, and more high‐cost hospitalizations (all P < 0.05). After risk adjustment, transplant hospitals were associated with higher mortality and high‐cost hospitalizations. In conclusion, CVD after liver transplant is evolving and responsible for growing rates of inpatient care. Transplant hospitals are associated with poor outcomes, even after risk adjustment for patient and hospital characteristics, which may be attributable to selective referral of certain patient phenotypes but could also be related to differences in quality of care. Further study is warranted.

AbstractIn endemic regions, coccidioidomycosis causes substantial morbidity and mortality for patients receiving solid organ transplants. We aimed to demonstrate the effect of antifungal coccidioidal prophylaxis in heart transplant (HT) recipients. We retrospectively reviewed the electronic health records of all patients who received HTs between October 19, 2005, and December 13, 2014. We collected information regarding antifungal regimens and determined whether patients subsequently developed infections. Our 174‐person cohort all received antifungal prophylaxis for at least 6 months (mean follow‐up, 53.8 months). One proven and one probable coccidioidal infection (each, 0.6%) occurred during the study period. The incidence of coccidioidomycosis was 0.6% at 1 year and 2.3% at 5 years. No cases of proven coccidioidomycosis occurred within 2 years after transplantation. No patients developed disseminated disease, and no sentinel events were attributed to coccidioidomycosis. Both fluconazole and voriconazole were well tolerated. In the absence of intolerance or contraindication, we suggest continuing a universal antifungal prophylactic regimen with fluconazole for at least 6‐12 months in HT recipients residing in a coccidioidomycosis‐endemic area.

Background Cardiovascular disease (CVD) is an important driver of mortality after kidney transplantation. Its broader impact on posttransplant health care utilization in US hospitals is unknown. Methods We used administrative claims data from the Nationwide Inpatient Sample and the American Hospital Association Annual Survey to identify hospitalizations for kidney transplant patients with a cardiovascular diagnosis from 2005 to 2011. CVD hospitalizations were stratified by transplant hospital status to characterize patterns in inpatient health care utilization and outcomes. Based on these analyses, the domestic burden of treatment for posttransplant CVD (myocardial infarction, stroke, congestive heart failure, dysrhythmia, cardiac arrest, malignant hypertension) was estimated. Results The total domestic burden of post-kidney transplant hospitalization between 2005 and 2011 is estimated at 389 138 of which 26.5% of episodes were related to CVD (n = 103 118). CVD was responsible for a growing proportion of post-transplant hospitalizations over time (24.4%-30.4%, P < 0.001). Compared with nontransplant hospitals, transplant hospitals had similar length of stay (median length of stay, 3.7 days), higher median costs per hospitalization (US $10 364 vs US $8606, overall US $9324), and lower adjusted mortality (3.2% vs 3.9%, overall 3.6%; P = 0.003). Conclusions Inpatient CVD care is increasing over time for kidney transplant patients, accounting for 30% of all post-transplant hospitalizations. Variation exists in the inpatient care, outcomes, and costs between by hospital type. Further studies are needed to better understand the mechanisms behind these phenomena.

Background— The HeartMate II (HMII) destination therapy (DT) trial demonstrated significant improvements in outcomes in continuous-flow left ventricular assist devices compared with patients implanted with the pulsatile-flow HeartMate XVE. The primary hypothesis of the current study is that trial patients enrolled after the initial data cohort would have better clinical outcomes. Methods and Results— Two hundred eighty-one patients who underwent HMII for DT from May 2007 to March 2009 (Mid Trial [MT] group) were compared with the initial 133 HMII patients from March 2005 to May 2007 (Early Trial [ET] group). Patient entry criteria were the same during the 2 time periods. Survival, adverse events, and quality of life were compared between the 2 groups. Baseline characteristics were similar between the groups. Compared with the ET group, patients in the MT group had reduced adverse event rates for bleeding requiring transfusions (1.66 versus 1.13 events per patient-year, P <0.001), sepsis (0.38 versus 0.27, P =0.025), device-related infections (0.47 versus 0.27, P <0.001), and hemorrhagic stroke (0.07 versus 0.03, P =0.01). Other event rates were similar between groups including ischemic stroke (0.06 versus 0.05 events per patient-year, P =0.57). Survival at 1 year in the MT group was 73% versus 68% in the ET group ( P =0.21). Additionally, there was a significant reduction in deaths caused by hemorrhagic stroke ( P =0.01). Quality of life improvements were significant in both the groups ( P <0.001). Conclusions— The benefit of DT therapy with the HMII is confirmed in subsequent trial patients, with improved adverse event rates and a strong trend for improvements in survival. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00121485.