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Aims Current non-invasive screening methods for cardiac allograft rejection have shown limited discrimination and are yet to be broadly integrated into heart transplant care. Given electrocardiogram (ECG) changes have been reported with severe cardiac allograft rejection, this study aimed to develop a deep-learning model, a form of artificial intelligence, to detect allograft rejection using the 12-lead ECG (AI-ECG). Methods and results Heart transplant recipients were identified across three Mayo Clinic sites between 1998 and 2021. Twelve-lead digital ECG data and endomyocardial biopsy results were extracted from medical records. Allograft rejection was defined as moderate or severe acute cellular rejection (ACR) based on International Society for Heart and Lung Transplantation guidelines. The extracted data (7590 unique ECG-biopsy pairs, belonging to 1427 patients) was partitioned into training (80%), validation (10%), and test sets (10%) such that each patient was included in only one partition. Model performance metrics were based on the test set (n = 140 patients; 758 ECG-biopsy pairs). The AI-ECG detected ACR with an area under the receiver operating curve (AUC) of 0.84 [95% confidence interval (CI): 0.78–0.90] and 95% (19/20; 95% CI: 75–100%) sensitivity. A prospective proof-of-concept screening study (n = 56; 97 ECG-biopsy pairs) showed the AI-ECG detected ACR with AUC = 0.78 (95% CI: 0.61–0.96) and 100% (2/2; 95% CI: 16–100%) sensitivity. Conclusion An AI-ECG model is effective for detection of moderate-to-severe ACR in heart transplant recipients. Our findings could improve transplant care by providing a rapid, non-invasive, and potentially remote screening option for cardiac allograft function.

Aims Increased LV wall thickness is frequently encountered in transthoracic echocardiography (TTE). While accurate and early diagnosis is clinically important, given the differences in available therapeutic options and prognosis, an extensive workup is often required to establish the diagnosis. We propose the first echo-based, automated deep learning model with a fusion architecture to facilitate the evaluation and diagnosis of increased left ventricular (LV) wall thickness. Methods and Results Patients with an established diagnosis of increased LV wall thickness (hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA), and hypertensive heart disease (HTN)/others) between 1/2015 to 11/2019 at Mayo Clinic Arizona were identified. The cohort was divided into 80%/10%/10% for training, validation, and testing sets, respectively. Six baseline TTE views were used to optimize a pre-trained InceptionResnetV2 model. Each model output was used to train a meta-learner under a fusion architecture. Model performance was assessed by multiclass area under the receiver operating characteristic curve (AUROC). A total of 586 patients were used for the final analysis (194 HCM, 201 CA, and 191 HTN/others). The mean age was 55.0 years, and 57.8% were male. Among the individual view-dependent models, the apical 4 chamber model had the best performance (AUROC: HCM: 0.94, CA: 0.73, and HTN/other: 0.87). The final fusion model outperformed all the view-dependent models (AUROC: CA: 0.90, HCM: 0.93, and HTN/other: 0.92). Conclusion The echo-based InceptionResnetV2 fusion model can accurately classify the main etiologies of increased LV wall thickness and can facilitate the process of diagnosis and workup.

Pectus excavatum is a common chest wall deformity with inward deviation of sternum and accompanying ribs. The depression can cause symptomatic cardiac compression, although the cardiopulmonary impact remains controversial. We present 2 cases of cardiac transplantation followed by modified minimally invasive pectus excavatum repair due to the hemodynamic consequences of the pectus deformity.

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.

Obesity is an important limiting factor for heart transplantation (HT) in patients with congestive heart failure (CHF). Achieving substantial weight loss is challenging in this population due to activity limitations and fluid retention. Endoscopic bariatric therapies (EBTs) including intragastric balloons (IGB) are effective primary weight loss therapies. IGBs have also been successfully utilized as a bridge therapy prior to liver transplantation and, in one case report, prior to HT. Potential advantages of IGBs in this population include low bleeding risk and less invasiveness as compared to other EBTs and surgery. We report the successful use of IGB as a bridge therapy in two patients with class II obesity and end-stage CHF requiring left ventricular assist devices (LVAD), anticoagulation, antiplatelet, and inotrope therapy.

This retrospective study analyzed glycemic trends, incidence of post-transplant diabetes mellitus (PTDM) incidence and associated risk factors in a cohort of patients who underwent first-time heart transplantation (HT). Univariate analyses compared patient with and without pretransplant diabetes mellitus (DM). Multivariate regression analyses were conducted to determine association between PTDM and different risk factors. Finally, trends in glucometrics and other outcomes are described across follow-up time points. There were 152 patients who underwent HT between 2010 and 2015, 109 of whom had no pretransplant history of DM. PTDM incidence was 38% by the 1-year follow-up. Pretransplant body mass index (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.01 to 1.23, p = 0.03), insulin use during the final 24 hours of inpatient stay (OR 4.26, 95% CI 1.72 to 10.56, p0.01), mean inpatient glucose (OR 2.21, 95% CI 1.33 to 3.69, p0.01), and mean glucose in the final 24 hours before discharge (OR 1.29, 95% CI 1.03 to 1.60, p = 0.03) were associated with increased odds of PTDM at 1 year. In patients on insulin before discharge, blood glucose values were significantly higher compared with those who were not (136 mg/dl vs 114 mg/dl at 1 to 3 months, 112 vs 100 at 4 to 6 months, 109 vs 98 at 8 to 12 months, all p0.01). This analysis improves understanding of PTDM incidence, glucometric trends, and risk differences by DM status in the HT population. Similar to liver and kidney patients, inpatient glucometrics may be informative of PTDM risk in HT patients. Guidelines for this population should be developed to account for risk heterogeneity and need for differential management.

Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce proliferation of lymphoid cells; thus, their use for immunosuppression after heart transplantation (HT) may reduce post-transplant lymphoproliferative disorder (PTLD) risk. This study sought to investigate whether the sirolimus (SRL)-based immunosuppression regimen is associated with a decreased risk of PTLD compared with the calcineurin inhibitor (CNI)-based regimen in HT recipients. We retrospectively analyzed 590 patients who received HTs at two large institutions between 1 June 1988 and 31 December 2014. Cox proportional-hazard modeling was used to examine the association between type of primary immunosuppression and PTLD after adjustment for potential confounders, including Epstein–Barr virus (EBV) status, type of induction therapy, and rejection. Conversion from CNI to SRL as primary immunosuppression occurred in 249 patients (42.2%). During a median follow-up of 6.3 years, 30 patients developed PTLD (5.1%). In a univariate analysis, EBV mismatch was strongly associated with increased risk of PTLD (HR 10.0, 95% CI: 3.8–26.6; p < 0.001), and conversion to SRL was found to be protective against development of PTLD (HR 0.19, 95% CI: 0.04–0.80; p = 0.02). In a multivariable model and after adjusting for EBV mismatch, conversion to SRL remained protective against risk of PTLD compared with continued CNI use (HR 0.12, 95% CI: 0.03–0.55; p = 0.006). In conclusion, SRL-based immunosuppression is associated with lower incidence of PTLD after HT. These findings provide evidence of a benefit from conversion to SRL as maintenance therapy for mitigating the risk of PTLD, particularly among patients at high PTLD risk.

Background Invasive fungal infection (IFI) in heart transplant recipients is associated with poor outcomes. Estimated risk of 1-year IFI in heart transplant recipients is 3.4-8.6% with risk factors inconsistently identified in previous studies. The role of antifungal prophylaxis is unclear. The transplant program at Mayo Clinic provides 6 months of universal azole prophylaxis for those heart transplant recipients in Arizona. We sought to define risk factors for 1-year IFI and determine the effect of antifungal prophylaxis. Methods We conducted a retrospective cohort study of patients undergoing heart transplantation at Mayo Clinic from January 2000 to March 2019. We analyzed demographics, details of transplant hospitalization, antifungal prophylaxis, and fungal infection. Multivariable Cox analyses were performed to identify risk factors of 1-year IFI and impact of IFI on posttransplant mortality. Results A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62). A total of 444 patients received antifungal prophylaxis. Over 1-year follow-up, 62 patients developed IFI with a cumulative incidence of 6.4%. In multivariable analysis, factors associated with IFI were renal replacement therapy (RRT) (HR 3.24, 95% CI 1.65-6.39), allograft rejection (HR 2.33, 95% CI 1.25-4.34), and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96). RRT was also associated with invasive mold infection (HR 3.00, 95% CI 1.29-6.97). Conclusions RRT and allograft rejection after transplantation are associated with 1-year IFI, and RRT is also associated with invasive mold infection. Antifungal prophylaxis appears to be protective and further study is needed in the heart transplant population.

Background: Patients presenting for kidney transplant (KTx) evaluation are subject to high rates of mortality and cardiovascular (CV) events pre- and post-KTx. CV and mortality risk assessment is needed. Methods: We evaluated cardiac troponin T (cTnT) as a predictor of CV events and mortality in a racially diverse cohort with significant CV disease burden presenting for KTx evaluation. Right ventricular systolic pressure (RVSP) was also assessed in predicting these outcomes. The population consisted of 561 patients presenting for KTx evaluation from 2011 to 2013 at Mayo Clinic, Arizona. A cutoff value for cTnT and RVSP that was most associated with CV events or mortality was derived. Multivariate Cox regression analysis was used to assess cTnT, RVSP, traditional, and other risk factors for the outcomes of interest. Results: Mean age was 53.5 ± 13.7 years and the median follow-up after KTx evaluation was 48.0 months. The cohort was 70.6% (n = 392) White, 11.4% (n = 63) Black, 8.5% (n = 47) Native American, and 3.1% (n = 17) Asian. Preexisting CV disease at the time of evaluation was prevalent in 24.4% (n = 137) of patients. During follow-up, 66.3% (n = 372) received a KTx and 21.9% (n = 123) had a composite event (16.8% death, 6.6 % CV events). It was found that 70.7% (n = 87) of events occurred in patients who were not transplanted; 53.5% (n = 300) had an elevated cTnT (≥0.01 ng/mL, median 0.02 ng/mL) and 84.1% (n = 344) of patients with RVSP data had an elevated RVSP (>25 mm Hg). Time to event analysis identified a cTnT ≥0.036 ng/mL and RVSP ≥31 mm Hg to be best predictive of CV events and mortality. Smoking, CV disease, hypoalbuminemia, RVSP, and cTnT independently predicted CV events and mortality. Conclusion: Elevated cTnT and RVSP were independently predictive of CV events and mortality in the cohort. Clinicians should consider the value of RVSP and cTnT as markers of CV risk in KTx evaluation.

Introduction: End stage renal disease (ESRD) patients with concomitant heart failure (HF) are often denied kidney transplantation (KTx). The aims of this study were to explore factors predictive of suitability for KTx and to assess cardiovascular (CV) outcomes in patients with impaired left ventricular ejection fraction (LVEF) presenting for KTx evaluation. Methods: We evaluated 109 consecutive adults with LVEF≤40% at the time of initial KTx evaluation between 2013 and 2018. Post-transplant CV outcomes were defined as non-fatal MI, admission for HF, CV death and all-cause mortality. Results: Mean age was 58.2 years (SD11.9), 78% were male, 58% had diabetes, 70% had history of CV events and 42% had ischemic cardiomyopathy. Mean LVEF was 31.5% (SD 6.47). Eighty patients had nuclear stress imaging; 10% were positive for reversible ischemia and 43% for prior infarct. Mean VO2max was 14.4(SD 5.71)ml/kg/min (31 patients). A cardiologist evaluated 93% of patients and was present at 58% of selection committee meetings. Twenty-four patients (22%) were denied by a cardiologist for KTx and 59 (54%) were denied by the selection committee, of whom 43 were due to CV risk. On univariate analysis, the variables associated with denial for KTx were: cardiologist denial, denial due to CV risk, Native American race (6% of cohort), higher NT-pro-BNP, prior MI, coronary intervention, positive stress study, anemia, lower EF and lower VO2max (all p Conclusions: Only 38% of ESRD patients with LVEF≤40% presenting for KTx evaluation were approved and of those, only 52% received KTx. Cardiologist approval was the primary predictor of suitability for KTx. Despite careful selection, prevalence of CV events and mortality after KTx was 23%. There is need for a consistent multidisciplinary approach during KTx evaluation, including cardiologist input, to improve CV outcomes.

Obesity is an important limiting factor for heart transplantation (HT) in patients with congestive heart failure (CHF). Achieving substantial weight loss is challenging in this population due to activity limitations and fluid retention. Endoscopic bariatric therapies (EBTs) including intragastric balloons (IGB) are effective primary weight loss therapies. IGBs have also been successfully utilized as a bridge therapy prior to liver transplantation and, in one case report, prior to HT. Potential advantages of IGBs in this population include low bleeding risk and less invasiveness as compared to other EBTs and surgery. We report the successful use of IGB as a bridge therapy in two patients with class II obesity and end-stage CHF requiring left ventricular assist devices (LVAD), anticoagulation, antiplatelet, and inotrope therapy.

As a bridge to heart transplantation or destination treatment, implantation of the Heartmate 3 (HM3) left ventricular assist device is a viable option for patients with end-stage congestive heart failure. The recent Momentum 3 trial has shown favorable outcomes compared with Heartmate 2. We report the first case of aortic root thrombus occurring early after HM3 implantation as a bridge to heart transplantation. Our case suggests that bridging with an Impella 5.0 preceding HM3 implantation could potentially predispose patients to aortic root thrombus after HM3 implantation, due to Impella-related injury to the aortic valve and aortic root stasis after durable LVAD support.

Background Kidney transplant (KT) patients presenting with cardiovascular (CVD) events are being managed increasingly in non-transplant facilities. We aimed to identify drivers of mortality and costs, including transplant hospital status. Methods Data from the 2009–2011 Nationwide Inpatient Sample, the American Hospital Association, and Hospital Compare were used to evaluate post-KT patients hospitalized for MI, CHF, stroke, cardiac arrest, dysrhythmia, and malignant hypertension. We used generalized estimating equations to identify clinical, structural, and process factors associated with risk-adjusted mortality and high cost hospitalization (HCH). Results Data on 7803 admissions were abstracted from 275 hospitals. Transplant hospitals had lower crude mortality (3.0% vs. 3.8%, p = 0.06), and higher un-adjusted total episodic costs (Median $33,271 vs. $28,022, p

Background Invasive fungal infection (IFI) in heart transplant recipients is associated with increased mortality and poor outcome. Reports have estimated the risk of 1-year IFI to be 3.4-8.6% with renal replacement therapy, delayed chest closure, and reoperation suggested as risk factors. However, the role of antifungal prophylaxis is unclear, though previous studies have suggested a reduced incidence of invasive Aspergillosis. The transplant program in Mayo Arizona provides 6 months of universal azole prophylaxis for Coccidioides, while Rochester and Florida only provide prophylaxis to high risk patients. We sought to define epidemiology and risk factors for 1-year IFI and determine the effect of antifungal prophylaxis. Methods We conducted a retrospective cohort study of patients undergoing single-organ heart transplantation at Mayo Rochester, Florida, or Arizona from January 2000 to March 2019. We identified baseline characteristics, details of transplant hospitalization such as need for renal replacement therapy, open chest, reoperation, and operative time, receipt of antifungal prophylaxis, and diagnosis of IFI. Multivariable Cox analysis was performed to identify risk factors of time to 1-year IFI. Results A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62) and 72% male. 444 patients received antifungal prophylaxis which included 32% fluconazole, 34% itraconazole, 18% voriconazole, 15% echinocandin, and < 1% amphotericin or posaconazole. Over 1-year follow-up, 62 patients developed IFI with a cumulative prevalence of 6.4%. The most common organisms were Aspergillus (50%) and Candida (27%). In a multivariable model, factors associated with 1-year IFI were post-transplant renal replacement therapy (HR 3.34, 95% CI 1.69-6.60; P < 0.001) and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96; P=0.042). Operative time, recent hospitalization, open chest, and post-transplant mechanical circulatory support were not associated with 1-year IFI. Conclusion Renal replacement therapy after transplantation is associated with 1-year IFI. Antifungal prophylaxis appears to be protective and further prospective study is warranted to verify this finding. Disclosures All Authors: No reported disclosures

Background Transthyretin amyloidosis (ATTR) is a heterogeneous disorder with multiorgan involvement and a genetic or nongenetic basis. Objectives The goal of this study was to describe ATTR in the United States by using data from the THAOS (Transthyretin Amyloidosis Outcomes Survey) registry. Methods Demographic, clinical, and genetic features of patients enrolled in the THAOS registry in the United States (n = 390) were compared with data from patients from other regions of the world (ROW) (n = 2,140). The focus was on the phenotypic expression and survival in the majority of U.S. subjects with valine-to-isoleucine substitution at position 122 (Val122Ile) (n = 91) and wild-type ATTR (n = 189). Results U.S. subjects are older (70 vs. 46 years), more often male (85.4% vs. 50.6%), and more often of African descent (25.4% vs. 0.5%) than the ROW. A significantly higher percentage of U.S. patients with ATTR amyloid seen at cardiology sites had wild-type disease than the ROW (50.5% vs. 26.2%). In the United States, 34 different mutations (n = 201) have been reported, with the most common being Val122Ile (n = 91; 45.3%) and Thr60Ala (n = 41; 20.4%). Overall, 91 (85%) of 107 patients with Val122Ile were from the United States, where Val122Ile subjects were younger and more often female and black than patients with wild-type disease, and had similar cardiac phenotype but a greater burden of neurologic symptoms (pain, numbness, tingling, and walking disability) and worse quality of life. Advancing age and lower mean arterial pressure, but not the presence of a transthyretin mutation, were independently associated with higher mortality from a multivariate analysis of survival. Conclusions In the THAOS registry, ATTR in the United States is overwhelmingly a disorder of older adult male subjects with a cardiac-predominant phenotype. Val122Ile is the most common transthyretin mutation, and neurologic phenotypic expression differs between wild-type disease and Val122Ile, but survival from enrollment in THAOS does not. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745)

BACKGROUND: Transthyretin amyloidosis (ATTR) is often associated with cardiac involvement manifesting as conduction disease as well as a restrictive cardiomyopathy causing heart failure and death. Myocardial contraction fraction (MCF), the ratio of left ventricular stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that is superior to EF in predicting mortality in patients with primary amyloid light chain (AL) cardiac amyloidosis. We hypothesized that MCF would be an independent predictor of survival in ATTR. METHODS AND RESULTS: MCF was derived from 2D echo-guided M-mode data for 530 subjects in the Transthyretin Amyloidosis Outcomes Survey (THAOS) database (age 61 ± 16, 74% male; 158 wild-type (ATTRwt) and 372 mutant (ATTRm) with a mean follow up of 1.5 ± 1.7 years). Using multivariate Cox proportional hazards regression models, MCF above and below 25% was highly associated with survival (HR 8.5, 95% CI 4.8 – 14.9, p < 0.0001) which was stronger than the association of ejection fraction (EF) dichotomized at 50% (HR 2.8, 95% CI 1.8 – 4.4, p < 0.0001). MCF < 25 % remained significantly predictive of survival in a multivariate model that included systolic blood pressure, estimated glomerular filtration rate below vs. above 65 ml/min/m(2), NYHA class, and health status based on the EQ-5D-3L questionnaire (AUC = 0.83, 95% CI 0.78 -0.89). CONCLUSIONS: MCF was superior to EF in predicting mortality in patients with transthyretin amyloidosis. A predictive model combining MCF with systolic blood pressure, renal function, NYHA class, and health status was strongly associated with survival in patients with ATTR.

Context Destination therapy (DT) patients face significant challenges as they transition from chronic left ventricular assist device (LVAD) support to comfort-oriented care. Integration of palliative medicine (PM) into the multidisciplinary team is important to facilitate advanced care planning (ACP) and improve quality of life (QoL). Objectives We evaluated the impact of a structured programmatic approach to the end-of-life (EOL) process in DT patients as measured by QoL surveys and the utilization of ACP. Methods We instituted a four prong intervention approach: 1) delineated the path from implant to EOL by defining specific stages, including a transitional phase where care limits were agreed upon, 2) standardized the role of PM, 3) held transitional care meetings to support shared decision-making, and 4) held multidisciplinary team debriefings to facilitate communication. Preintervention and postintervention outcomes were measured for patients/caregivers by using the QUAL-E/QUAL-E (family) QoL instrument. Wilcoxon signed-ranks test compared nonparametric variables. Results All patients (n = 41)/caregivers (n = 28) reported improved QoL measures (patient P = 0.035/caregiver P = 0.046). Preparedness plans increased from 52% to 73% after implementation and advance directives increased from 71% to 83%. Fifty-nine percent of the patients completed an outpatient PM clinic visit; 51% completed/scheduled a second visit. Clinician outcomes improved including satisfaction with multidisciplinary team communication/expectations, ACP processes, and EOL management. Conclusion A programmatic approach that standardizes the role of PM and delineates the patient's path from implant to EOL improved quality outcomes and increased implementation of ACP. A defined communication process allowed the multidisciplinary team to have a clear patient management approach.

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 a priori dichotomization of the VO 2peak 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.

Purpose Historically, survival after heart transplantation (HT) has been inferior among patients bridged with ECMO. With the recent changes in US heart allocation policy, VA-ECMO is now a status 1 indication for HT. We sought to explore the potential implications of these changes by evaluating outcomes among patients bridged to HT with ECMO. Methods We sampled HT recipients enrolled through the UNOS database from 1987 to 2017. Re-transplants were excluded, and patients were divided into two age groups: 18 years (adults ). Patients in each age group were categorized as those bridged with ECMO vs No-ECMO, and demographics between ECMO and No-ECMO patients were analyzed with Wilcoxon and Chi-Square tests . Overall survival time was analyzed with Kaplan-Meier, and compared between groups using Log-rank tests. Survival was also assessed >90 days post-transplant. Results Our sample consisted of 8,334 juveniles (414 ECMO, 7,920 No-ECMO), mean age 6.1 years and 56,013 adults (189 ECMO, 55824 No-ECMO), mean age 52.1 years. In both groups, recipient and donor ages differed between ECMO and No-ECMO patients (p 90 days). Conclusion Survival after HT with ECMO bridging is significantly lower among both juveniles and adults, though differences disappeared after 90 days. Limitations include small number of adults undergoing ECMO bridging. In light of the new HT allocation policy, as well as a lack of donor organs and notable waitlist mortality, alternate bridging options could be considered. This is particularly true among adult populations, where other options exist.

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 (P0.01). CVA and MI declined over time (both P0.05), but CHF and dysrhythmia grew significantly (both P0.03); a total of 19% of hospitalizations were for multiple CVD diagnoses. Transplant hospitals had lower comorbidity patients (P0.001) and greater resource intensity including presence of cardiac intensive care unit, interventional radiology, operating rooms, teaching status, and nursing density (all P0.01). Transplant and nontransplant hospitals had similar unadjusted mortality (overall, 3.9%, P = 0.55; by diagnosis, all P0.07). Transplant hospitals had significantly longer overall length of stay, higher total costs, and more high-cost hospitalizations (all P0.05). 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.

Invasive mucormycosis infections occur in less than 1% of recipients of orthotopic heart transplants. Given the angioinvasive nature of these infections, the mortality rate is high. Little literature exists regarding the presentation and management of these infections. We present a case of a patient who developed an infection after orthotopic heart transplant, describe the successful multidisciplinary management surrounding his care, and review the available literature regarding mucormycosis infections in heart transplant recipients.

Background Solubility of Tumorigenicity 2 (sST2) is a novel biomarker that better stratifies risk of cardiovascular events (CVE) compared to cardiac troponin T(cTnT) in heart failure. We assessed the association of sST2 with the composite outcome of CVE and/or mortality compared to cTnT in kidney transplant candidates. Methods 200 kidney transplant candidates between 2010 and 2013 were included. Elevated sST2 was defined as ≥30ng/ml, cTnT≥0.01 ng/ml. Results Median age 53 (interquartile range (IQR) 42–61) years, 59.7% male and 82.0% white. 33.5% had history of CVE, 42.5% left ventricular hypertrophy (LVH) and 15.6% positive cardiac stress test. Elevated sST2 correlated with male gender, history of prior-transplants, CVE, positive stress test, LVH, elevated cTnT, anemia, hyperphosphatemia, increased CRP and non-transplanted status. Male gender, history of CVE and LVH were independent determinants of sST2. During 28 months (IQR 25.3–30), 7.5% died, 13.0% developed CVE and 19.0% developed the composite outcome. Elevated sST2 was associated with the composite outcome (hazard ratio = 1.76, CI 1.06–2.73, p = 0.029) on univariate analysis but not after adjusting for age, diabetes and cTnT (p = 0.068). sST2 did not change the risk prediction model for composite outcome after including age, diabetes, prior history of CVE and elevated cTnT. Conclusions Increased sST2 level is significantly associated with variables associated with CVE in kidney transplant candidates. sST2 was associated with increased risk of the composite outcome of CVE and/or death but not independent of cTnT. Larger studies are needed to confirm these findings and determine whether sST2 has added value in CV risk stratification in this cohort of patients.

Activation of the sympathetic nervous system (SNS) is a fundamental component of the pathophysiology of heart failure, especially heart failure with reduced ejection fraction (HFREF). Prolonged SNS activation contributes to several of the clinical sequelae of HFREF, such as loss of contractile reserve, ventricular remodeling, and sudden cardiac death. Over the last 30 years, extensive clinical research has shown that inhibition of the SNS in patients with heart failure improves outcomes including mortality, hospitalization for heart failure, progression of symptoms, and sudden cardiac death. The cornerstone therapy for inhibiting the SNS is administration of drugs that act as antagonists of the β-adrenergic receptor (β-blockers). A robust body of evidence shows that β-blockers reduce symptoms and improve outcomes in all patients with HFREF. Non-pharmacologic therapies that also have been found to improve outcomes in patients with heart failure, such as cardiac resynchronization therapy (CRT) and exercise training, mediate their beneficial effects via inhibition of the SNS. Here, we review the literature that supports the use of these pharmacologic and non-pharmacologic therapies and offer practical advice regarding their application in clinical care.

Background Drive-line infections and sepsis lead to significant morbidity and even mortality in patients with ventricular assist devices (VADs). The HeartWare HVAD system is unique compared with other VAD systems in that it has a thin, flexible drive-line and is implanted directly into the pericardial space without the need for a pump pocket. We reviewed 332 patients receiving the HVAD in the pivotal ADVANCE Bridge to Transplant (BTT) trial and Continued Access Protocol (CAP) to determine the incidence of drive-line infections and sepsis. Methods Summary statistics of outcomes and Kaplan–Meier freedom-from-event analyses were performed. The Cochran–Mantel–Haenszel test for homogeneity was used to determine whether there was any site effect on rates of either drive-line exit-site or sepsis infections. Results Drive-line exit-site infections occurred in 16.9% (56 of 332) of patients (0.25 event per patient-year [EPPY]). These infections were primarily treated with antibiotics and most occurred >30 days post-implant (88%, or 66 of 75 drive-line infections). Sepsis occurred in 17.2% (57 of 332) of patients (0.23 EPPY), and sepsis events occurred more frequently >30 days post-implant (86%, or 60 of 70 sepsis events). Of patients with sepsis, 17.5% (10 of 57) died due to sepsis-related neurologic events (7 of 10) and multisystem organ failure (2 of 10) and cardiopulmonary failure (1 of 10), whereas there were no deaths related to drive-line infections. In addition, 17.5% (10 of 57) of patients had a stroke event while under treatment for sepsis (7 hemorrhagic and 3 ischemic strokes), and 3.5% (2 of 57 patients with sepsis) had a device exchange for VAD thrombus (4 days before and 1 day after sepsis diagnosis). Patients with drive-line infections or sepsis had a larger body mass index compared to those without infection (29.4 vs 27.6 kg/m 2 , p = 0.015), and were more frequently diabetic (43.7% vs 31.2%, p = 0.034). Although there was no negative impact on survival in patients with drive-line exit-site infections, there was a trend for reduced survival in patients with sepsis events when compared to those patients without sepsis. Conclusions The incidence of drive-line infection and sepsis was low in patients receiving the HVAD pump. Despite a trend toward reduced survival in patients with sepsis events, the overall survival of patients with either drive-line infections or sepsis was excellent.

In 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. This article is protected by copyright. All rights reserved.

Few studies address the potential for donation after brain death (DBD) in the limited population of patients with ongoing mechanical circulatory support (MCS). A case study was conducted reviewing available records of both donor and recipient, and available literature. The donor was a young female with an acute myocardial infarction precipitating emergent off-pump 2-vessel bypass graft complicated by profound cardiogenic shock refractory to inotropes and intra-aortic balloon pump. A heparin drip was started following percutaneous placement of a left ventricular-assist device (TandemHeart?) which improved her hemodynamics to stabilize for transfer. She ultimately required surgical placement of biventricular assist device (CentraMag?) to normalize hemodynamics. Two days post-operatively, she developed a cerebellar hemorrhage and was declared brain dead. Pre-donation blood chemistry showed adequate end-organ function. Both kidneys were placed locally. The liver was rejected for two regional status 1 patients and by all other local centers. We accepted the liver for a patient with polycystic liver disease with a MELD exception score of 20. The recipient is now 4 years post-transplant with excellent graft function. Extending donor criteria to include MCS patients can result in successful transplantation and should be considered in selected circumstances once satisfactory donor end-organ function is established.

Background Sensitized heart transplant candidates spend more time and have higher mortality on the waiting list. Although the calculated panel-reactive antibody (CPRA) value is used to assign allocation priority to kidney transplant candidates in the United States, the relationship between CPRA and outcomes on the heart transplant waiting list is unknown. Methods A data set of patients listed for heart transplant with unacceptable human leukocyte antigens (HLA) entered was obtained from the United Network for Organ Sharing. The study cohort was composed of 3,855 adult candidates listed for heart transplant between 2006 and 2013 with active waiting time. The cohort was divided into 5 groups by increasing CPRA. Outcomes were assessed using competing risks and sub-hazard regression analyses. Results In each group of successively higher CPRA, the percentage of candidates who received a transplant decreased, whereas the percentage of those who were still waiting for a transplant increased, as did the percentage of those removed from the waiting list or had died. The group of candidates with a CPRA >80% displayed a markedly decreased incidence of transplantation (hazard ratio 0.37) and an increased risk of removal from the waiting list or death (hazard ratio 2.18) as compared to those with CPRA of ≤10%. Conclusions Sensitized heart transplant candidates are at high risk of adverse outcomes on the heart transplant waiting list. Clinicians should strive to minimize the CPRA by maximizing specificity in the selection of HLA antigens to exclude. The optimal clinical approach for candidates with high CPRA requires further study.

Left ventricular assist devices (LVAD) are being deployed increasingly in patients with severe left ventricular dysfunction and medically refractory congestive heart failure of any etiology. The United States Food and Drug Administration (FDA) recently approved the use of the Thoratec Heartmate II (Thoratec Corporation, Pleasanton, CA, USA) for outpatient use. Echocardiography is fundamental during each stage of patient management, pre-LVAD placement, during LVAD placement, for postoperative LVAD optimization and long-term follow-up. We present a pragmatic and systematic echocardiographic approach that serves as a guide for the management of left ventricular assist devices.

Background Owing to inconsistent diagnostic criteria and small heterogeneous cohorts, little is known about the long-term outcomes of adult left ventricular noncompaction (LVNC), a rare cardiomyopathy with potentially serious outcomes. This systematic overview aimed to better delineate the natural history of adult LVNC. Method and Results A comprehensive computerized search using “noncompaction” and its synonyms initially identified 206 articles, with reference lists subsequently hand scanned. These searches yielded 5 studies that were eligible for this systematic overview, identifying adult cohorts with isolated LVNC diagnosed by similar echocardiographic criteria. This combined cohort (n = 241) was followed for a mean duration of 39 months. The annualized event rate was 4% for cardiovascular deaths, 6.2% for cardiovascular death and its surrogates (heart transplantation and appropriate implantable cardioverter-defibrillator shocks), and 8.6% for all cardiovascular events (death, stroke, implantable cardioverter-defibrillator shocks, and heart transplantation.) Familial occurrence of LVNC in first-degree relatives was identified by echocardiography in 30% of index cases who were screened. Conclusion LVNC is an increasingly recognized cardiomyopathy diagnosed by echocardiography and is associated with familial tendencies, arrhythmias, thromboembolism, advanced heart failure, and death.

Objectives The aim of this study was to explore the temporal evolution of left ventricular (LV) mechanics in relation to clinical variables and genetic expression profiles implicated in cardiac allograft function. Background Considerable uncertainty exists regarding the range and determinants of variability in LV systolic performance in transplanted hearts (TXH). Methods Fifty-one patients (mean age 53 ± 12 years; 37 men) underwent serial assessment of echocardiograms, cardiac catheterization, gene expression profiles, and endomyocardial biopsy data within 2 weeks and at 3, 6, 12, and 24 months after transplantation. Two-dimensional speckle-tracking data were compared between patients with TXH and 37 controls (including 12 post–coronary artery bypass patients). Post-transplantation mortality and hospitalizations were recorded with a median follow-up period of 944 days. Results Global longitudinal strain (LS) and radial strain remained attenuated in patients with TXH at all time points (p Conclusions Speckle tracking–derived LV strains are helpful in estimating the burden of LV dysfunction in patients with TXH that evolves independent of biopsy-detected cellular rejection. Failure to improve global LS at 3 months after transplantation is associated with a higher incidence of death and cardiac events. Serial changes in LV mechanics correlate with peripheral blood gene expression profiles and may affect the clinical assessment of long-term prognosis in patients with TXH.

Pectus excavatum (PE) is a posterior depression of the sternum and adjacent costal cartilages and is frequently seen by primary care providers. PE accounts for >90% of congenital chest wall deformities. Patients with PE are often dismissed by physicians as having an inconsequential problem; however, it can be more than a cosmetic deformity. Severe cases can cause cardiopulmonary impairment and physiologic limitations. Evidence continues to present that these physiologic impairments may worsen as the patient ages. Data reports improved cardiopulmonary function after repair and marked improvement in psychosocial function. More recent consensus by both the pediatric and thoracic surgical communities validates surgical repair of the significant PE and contradicts arguments that repair is primarily cosmetic. We performed a review of the current literature and treatment recommendations for patients with PE deformities.

ObjectivesWe explored the incremental value of quantification of tissue Doppler (TD) velocity during the brief isovolumic contraction (IVC) phase of the cardiac cycle for the prediction of exercise performance in patients referred for cardiopulmonary exercise testing (CPET).BackgroundExperimental studies have shown that rapid left ventricular (LV) shape change during IVC is essential for optimal onset of LV ejection. However, the incremental value of measuring IVC velocities in clinical settings remains unclear.MethodsA total of 82 subjects (age 53 ± 14 years, 56 men) were studied with echocardiography and CPET. Reduced LV ejection fraction (EF) (EF

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.

Reports documenting the cardiopulmonary significance of pectus excavatum are limited, and there remains a lack of consensus as to whether surgical repair can improve function. We present a case of pectus excavatum deformity and heart failure. Surgical repair was performed with significant improvement of performance and heart function.

Cases of transient left ventricular apical ballooning during dobutamine stress echocardiography have been described in the literature. Dobutamine may contribute to this phenomenon via excess catecholamine release, similar to the proposed mechanism of apical ballooning syndrome during states of extreme emotional stress. We report the first case of reversible severe left ventricular systolic dysfunction with an apical ballooning pattern during dobutamine stress echocardiography in a patient who had undergone orthotopic heart transplantation.

Background In young children, acquired thoracic dystrophy (ATD) is associated with extensive resection of cartilage, often during open pectus excavatum (PE) repair. Progressive dyspnea or exercise intolerance may develop in these patients secondary to cardiac compression or restrictive pulmonary function. Surgical treatment of ATD by attempting to increase the overall thoracic volume has been controversial. We describe our experience with adults presenting for surgical correction of ATD. Methods A retrospective medical record review was performed for all patients with ATD presenting for surgical evaluation from December 2010 through February 2013. Results Ten adult male patients were evaluated for treatment of ATD after an open Ravitch procedure for PE. Nine patients, whose mean age was 34 years (range, 21-42 years), elected to proceed with surgical treatment. The mean age of the initial repair was 3.7 years. Extensive reconstruction, chest wall expansion, and placement of stainless steel support bars and titanium plating were performed in all patients. Eight patients had minor complications, and major complications occurred in 3 patients. Respiratory failure with prolonged ventilator support occurred in 3 patients. There were no reoperations or deaths. At mean follow-up of 16 months (range, 6-31 months), all patients subjectively reported improvement in their ability to exercise and in their symptoms, including dyspnea with exertion. Conclusions ATD may be associated with early childhood Ravitch repair. Adults may present with disabling symptoms related to cardiac compression and restrictive pulmonary function. Reconstruction with sternal elevation and expansion of the anterior chest subjectively improves symptoms.

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 P =0.025), device-related infections (0.47 versus 0.27, P 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 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.