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Background: Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF. Methods: Patients implanted with continuous flow LVAD between June 2, 2014, and June 30, 2016 and registered in the Interagency Registry for Mechanically Assisted Circulatory Support/Society of Thoracic Surgeons Database were included. RHF incidence and predictors, and survival after RHF were assessed. The manifestations of RHF which were separately analyzed were elevated central venous pressure, peripheral edema, ascites, and use of inotropes. Results: Among 5537 LVAD recipients (mean 57±13 years, 49% destination therapy, support 18.9 months) prevalence of 1-month RHF was 24%. Of these, RHF persisted at 12 months in 5.3%. In contrast, de novo RHF, first identified at 3 months, occurred in 5.1% and persisted at 12 months in 17% of these, and at 6 months occurred in 4.8% and persisted at 12 months in 25%. Higher preimplant blood urea nitrogen (ORs,1.03–1.09 per 5 mg/dL increase; P P P =0.004); and centrifugal versus axial LVAD (ORs,1.15–1.78; P =0.001) represented risk factors for RHC incidence at 3 months. Patients with persistent RHF at 3 months had the lowest 2-year survival (57%) while patients with de novo RHF or RHF which resolved by 3 months had more favorable survival outcomes (75% and 78% at 2 years, respectively; P Conclusions: RHF at 1 or 3 months post-LVAD was a common and frequently transient condition, which, if resolved, was associated with relatively favorable prognosis. Conversely, de novo, late RHF post-LVAD (>6 months) was more frequently a persistent disorder and associated with increased mortality. The 1-, 3-, and 6-month time points may be used for RHF assessment and risk stratification in LVAD recipients.

Background The COVID-19 pandemic disrupted the way care is delivered to patients with chronic conditions such as heart failure (HF). Many outpatient encounters are now conducted virtually via telehealth. Whether virtual visit for HF results in similar type of interventions as when the patient is seen in person is not known. Methods Starting on March 15, 2020, all non-time sensitive outpatient in-person appointments at our institution were cancelled and transitioned to virtual appointments where possible. We included all patients seen in a tertiary care HF clinic from February 18 to March 13 (pre-Covid) and from March 16 to May 15 (post-COVID). We examined the volume of in-person and virtual visits and compared medication titration rates pre- and post-COVID. Results The study cohort included 745 patients, mean age 60.7+/-15.3 years, 65.2% male, 80.9% Caucasian, 7.7% Hispanic/Latino. Of these, 227 patients were seen pre-COVID and 518 post-COVID. All appointments were in-person pre-COVID. After the change, only 18% of appointments were in-person while 82% were virtual. Outpatient volume decreased after March 15, but gradually increased, eventually to volumes that exceeded pre-COVID (Figure). Detailed results on medication titration are shown in Table. Diuretic titration took place in 33/227 (14.5%) of patients pre-COVID and 83/518 (16.0%) post-COVID (p=NS). Among 567 patients with HF with reduced ejection fraction (HFrEF), titration of guideline-directed medical therapy (GDMT) took place in 86/172 (50.0%) of patients pre-COVID and 159/395 (40.2%) post-COVID (p=0.03). Among the 395 HFrEF patients seen post-COVID, GDMT was titrated in 33/68 (48.5%) patients seen in person and 126/327 (38.5%) seen virtually - p=0.13. Barriers to medication titration in virtual visits were lack of blood pressure readings and lack of recent laboratory results. Conclusion Telehealth has become an essential method of outpatient care delivery for chronic HF. Once implemented, it offered efficiencies including improved access to the HF clinic thanks to higher throughput capacity compared to physical clinic space. However, we identified that GDMT titration took place less frequently than during in-person visits. Since it is anticipated that telehealth use will continue into the future, approaches to maximize GDMT in the absence of traditional direct physical contact with HF patients are needed.

SUMMARY Using serial analysis of myocardial gene expression employing endomyocardial biopsy starting material in a dilated cardiomyopathy cohort, we show that the SARS-CoV-2 cardiac myocyte receptor ACE2 is upregulated with remodeling and with reverse remodeling down-regulates into the normal range. The proteases responsible for virus-cell membrane fusion were expressed but not regulated with remodeling. In addition, a new candidate for CoV-2 cell binding and entry was identified, the integrin ITGA5. The upregulation in ACE2 in remodeled LVs may explain worse outcomes in COVID-19 patients with underlying myocardial disorders, and counteracting ACE2 upregulation is a possible therapeutic approach to minimizing cardiac damage., Graphical abstract, Highlights 1. The SARS-CoV-2 cellular receptor ACE2 and 5 proteases implicated in fusion of virus and cell membranes that are vital to cell entry were expressed at the mRNA level in RNA extracted from septal endomyocardial biopsies of F/NDC and nonfailing (NF) control patients. 2. ACE 2 was upregulated by 1.97 fold in 46 F/NDC patients compared to NF, but proteases showed similar degrees of expression. 3. On LV reverse remodeling effected by beta-blocking agents, ACE2 expression, in the presence of unchanged doses of ACE inhibitors or ARBs, downregulated into the normal range. 4. ITGA5, an integrin that binds to ACE2 and to a motif in the CoV-2 spike protein binding domain, was expressed in both NF and F/NDC, upregulated in the latter at baseline and decreased in expression on reverse remodeling similar to ACE2, and is a candidate for facilitating CoV-2 binding and cell entry in LV myocardium.

Purpose The complex anatomy and different contraction patterns of the different right ventricular (RV) wall segments has made it challenging to predict acute RV failure (ARVF) in patients receiving a left ventricular assist device (LVAD). We sought to improve the prediction of ARVF after LVAD by performing a comprehensive 18-segment strain (e) analysis of the RV. Methods Prospectively enrolled LVAD recipients had a right heart catheterization and echocardiogram prior to implant. From RV-focused views (Figure 1A), 18-segment e was performed and indexed to pulmonary arterial elastance (Ea [PV]). ARVF was defined as need for RVAD, inotropes for >14 days or pulmonary vasodilator for >48 hours post-LVAD. Logistic regression was used to identify associations between specific parameters and ARVF. Results ARVF occurred in 15 of 30 patients enrolled. Lower pulmonary artery pulsatility index (PAPi), TAPSE and basal free wall (FW) (basal anterior, lateral and posterior FW) segmental e/Ea (PV) were significantly associated with ARVF. Indexed basal FW segmental strain provided incremental predictive value over PAPi and TAPSE (Figure 1B). Conclusion Prediction of ARVF in LVAD candidates can be improved by adding comprehensive RV segmental strain analysis to traditional echocardiographic and hemodynamics parameters.

Importance Heart failure with recovered ejection fraction (HFrecEF) is a recently recognized phenotype of patients with a history of reduced left ventricular ejection fraction (LVEF) that has subsequently normalized. It is unknown whether such LVEF improvement is associated with improvements in health status. Objective To examine changes in health-related quality of life in patients with heart failure with reduced ejection fraction (HFrEF) whose LVEF normalized, compared with those whose LVEF remains reduced and those with HF with preserved EF (HFpEF). Design, setting, and participants This prospective cohort study was conducted at a tertiary care hospital from November 2016 to December 2018. Consecutive patients seen in a heart failure clinic who completed patient-reported outcome assessments were included. Clinical data were abstracted from the electronic health record. Data analysis was completed from February to December 2020. Main outcomes and measures Changes in Kansas City Cardiomyopathy Questionnaire overall summary score, Visual Analog Scale score, and Patient-Reported Outcomes Measurement Information System domain scores on physical function, fatigue, depression, and satisfaction with social roles over 1-year follow-up. Results The study group included 319 patients (mean [SD] age, 60.4 [15.5] years; 120 women [37.6%]). At baseline, 212 patients (66.5%) had HFrEF and 107 (33.5%) had HFpEF. At a median follow-up of 366 (interquartile range, 310-421) days, LVEF had increased to 50% or more in 35 patients with HFrEF (16.5%). Recovery of systolic function was associated with heart failure-associated quality-of-life improvement, such that for each 10% increase in LVEF, the Kansas City Cardiomyopathy Questionnaire score improved by an mean (SD) of 4.8 (1.6) points (P = .003). Recovery of LVEF was also associated with improvement of physical function, satisfaction with social roles, and a reduction in fatigue. Conclusions and relevance Among patients with HFrEF in this study, normalization of left ventricular systolic function was associated with a significant improvement in health-related quality of life.

Diagnosis, prognosis, treatment, and development of new therapies for diseases or syndromes depend on a reliable means of identifying phenotypes associated with distinct predictive probabilities for these various objectives. Left ventricular ejection fraction (LVEF) provides the current basis for combined functional and structural phenotyping in heart failure by classifying patients as those with heart failure with reduced ejection fraction (HFrEF) and those with heart failure with preserved ejection fraction (HFpEF). Recently the utility of LVEF as the major phenotypic determinant of heart failure has been challenged based on its load dependency and measurement variability. We review the history of the development and adoption of LVEF as a critical measurement of LV function and structure and demonstrate that, in chronic heart failure, load dependency is not an important practical issue, and we provide hemodynamic and molecular biomarker evidence that LVEF is superior or equal to more unwieldy methods of identifying phenotypes of ventricular remodeling. We conclude that, because it reliably measures both left ventricular function and structure, LVEF remains the best current method of assessing pathologic remodeling in heart failure in both individual clinical and multicenter group settings. Because of the present and future importance of left ventricular phenotyping in heart failure, LVEF should be measured by using the most accurate technology and methodologic refinements available, and improved characterization methods should continue to be sought.

Aims This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS-986231, a novel second-generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF). Methods and results Forty-six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose-escalation cohorts in this double-blind, randomized, placebo-controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m2 received one 6-h i.v. infusion of BMS-986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS-986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time-averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS-986231 increased non-invasively measured time-averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug-related arrhythmia or symptomatic hypotension with BMS-986231. Analyses of adverse events throughout the 30-day follow-up did not identify any toxicities specific to BMS-986231, with the potential exception of infrequent mild-to-moderate headaches during infusion. There were no treatment-related serious adverse events. Conclusions BMS-986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS-986231 should be further assessed in patients with heart failure.

Aims This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS‐986231, a novel second‐generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF). Methods and results Forty‐six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose‐escalation cohorts in this double‐blind, randomized, placebo‐controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m2 received one 6‐h i.v. infusion of BMS‐986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS‐986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time‐averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS‐986231 increased non‐invasively measured time‐averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug‐related arrhythmia or symptomatic hypotension with BMS‐986231. Analyses of adverse events throughout the 30‐day follow‐up did not identify any toxicities specific to BMS‐986231, with the potential exception of infrequent mild‐to‐moderate headaches during infusion. There were no treatment‐related serious adverse events. Conclusions BMS‐986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS‐986231 should be further assessed in patients with heart failure.

Purpose LVAD therapy has been primarily studied in patients with elevated pulmonary capillary wedge pressure (PCW) and low cardiac index (CI), “cold and wet”. In daily practice, LVADs are often also offered to patients with low PCW and low CI, “cold and dry”. The efficacy of LVAD therapy in this population is not well studied. Methods Patients implanted with LVAD with a baseline CI 18mmHg) or “dry” (PCW Results Serial invasive hemodynamics data was available for 92 pts (cold-dry group, n=34 and cold-wet group, n=58) (Table). Diuretic and vasodilator use pre-LVAD was comparable in both groups. Cold-dry patients had no change in CVP or PCW with a smaller increase in CI after LVAD. Adjusted 3-year mortality was higher for cold-dry patients (Figure). Age (HR=1.09, 95%CI 1.02-1.2; p=006) and cold-dry profile (HR=5.4, 95%CI 1.4-21; p=0.016) were identified as independent predictors of mortality. Conclusion “Cold and dry” patients with advanced heart failure may not derive equal benefit from LVAD therapy as those who are “cold and wet”. This observation warrants further investigation.

Objectives The aim of this study was to evaluate the impact of a shared-care model on outcomes in patients with left ventricular assist devices (LVADs) living in remote locations. Background Health care delivery through shared-care models has been shown to improve outcomes in patients with chronic diseases. However, the impact of shared-care models on outcomes in patients with LVAD is unknown. Methods LVAD recipients in the authors’ program (2007 to 2018) were classified based on the levels of care provided and training and resources used: level 1, was defined as outpatient primary care without LVAD-specific care; level 2 was level 1 services and outpatient LVAD-specific care; level 3 was level 2 services and inpatient LVAD-specific care and implantation center (IC). The Kaplan-Meier method was used to compare rates of survival, bleeding, pump thrombosis, infection, neurologic events, and readmissions among levels of care. Results A total of 336 patients were included, with 255 patients (75.9%) cared for in shared-care facilities. Median follow-up was 810 (interquartile range: 321 to 1,096) days. In comparison to patients cared for by IC, patients at levels 2 and 3 shared-care centers had similar rates of death, bleeding, neurologic events, pump thromboses, and infections. However, the rates of death, pump thromboses, and infections were higher for level 1 patients than in IC patients. Conclusions Shared health care is an effective strategy to deliver care to patients with LVAD living in remote locations. However, patients in shared-care facilities unable to provide LVAD-specific care are at higher risk of unfavorable outcomes. Availability of LVAD-specific care should be strongly considered during patient selection and every effort made to ensure LVAD-specific training and resources are available at shared-care facilities.

Background Predicting cardiac recovery (CR) in advanced heart failure (HF) patients before left ventricular assist device (LVAD) implantation remains challenging. This study sought to investigate whether CR after LVAD unloading can be predicted by cardiac functional and structural parameters together with clinical characteristics. Methods From 2008 to 2016, consecutive advanced chronic HF patients (N=347) supported with durable continuous-flow LVADs were prospectively evaluated. Patients with acute HF etiologies or without adequate post-LVAD follow up ( Results CR occurred in 13.7% of patients. Univariate analysis showed that responders were more likely to be young, female, non-ischemic cardiomyopathy, with shorter HF symptoms duration and no prior cardiac surgery. They had lower blood urea nitrogen and were more likely to be on temporary mechanical support before LVAD. The multivariable UCAR model (AUC=0.755; p Conclusion Univariate and multivariable predictors of CR include both modifiable and non-modifiable patient characteristics that are known prior to LVAD implantation. The UCAR score can serve as a practical tool for targeted patient selection to implement protocols that facilitate CR in the advanced HF patient subpopulation that is most likely to respond.

ObjectivesTo investigate the biologic relevance of cross-platform concordant changes in gene expression in intact human failing/hypertrophied ventricular myocardium undergoing reverse remodeling.BackgroundInformation is lacking on genes and networks involved in remodeled human LVs, and in the associated investigative best practices.MethodsWe measured mRNA expression in ventricular septal endomyocardial biopsies from 47 idiopathic dilated cardiomyopathy patients, at baseline and after 3-12 months of β-blocker treatment to effect left ventricular (LV) reverse remodeling as measured by ejection fraction (LVEF). Cross-platform gene expression change concordance was investigated in reverse remodeling Responders (R) and Nonresponders (NR) using 3 platforms (RT-qPCR, microarray, and RNA-Seq) and two cohorts (All 47 subjects (A-S) and a 12 patient "Super-Responder" (S-R) subset of A-S).ResultsFor 50 prespecified candidate genes, in A-S mRNA expression 2 platform concordance (CcpT), but not single platform change, was directly related to reverse remodeling, indicating CcpT has biologic significance. Candidate genes yielded a CcpT (PCR/microarray) of 62% for Responder vs. Nonresponder (R/NR) change from baseline analysis in A-S, and ranged from 38% to 100% in S-R for PCR/microarray/RNA-Seq 2 platform comparisons. Global gene CcpT measured by microarray/RNA-Seq was less than for candidate genes, in S-R R/NR 17.5% vs. 38% (P = 0.036). For S-R global gene expression changes, both cross-cohort concordance (CccT) and CcpT yielded markedly greater values for an R/NR vs. an R-only analysis (by 22 fold for CccT and 7 fold for CcpT). Pathway analysis of concordant global changes for R/NR in S-R revealed signals for downregulation of multiple phosphoinositide canonical pathways, plus expected evidence of a β1-adrenergic receptor gene network including enhanced Ca2+ signaling.ConclusionsTwo-platform concordant change in candidate gene expression is associated with LV biologic effects, and global expression concordant changes are best identified in an R/NR design that can yield novel information.

Background Immune allosensitization can be triggered by continuous-flow left ventricular assist devices (CF LVAD). However, the effect of this type of allosensitization on post-transplant outcomes remains controversial. This study examined the post-transplant course in a contemporary cohort of patients undergoing transplantation with and without LVAD bridging. Methods We included consecutive patients who were considered for cardiac transplant from 2006 to 2015. Serum alloantibodies were detected with single-antigen beads on the Luminex platform (One Lambda Inc., Canoga Park, CA). Allosensitization was defined as calculated panel reactive antibody (cPRA) > 10%. cPRA was determined at multiple times. LVAD-associated allosensitization was defined as development of cPRA > 10% in patients with cPRA ≤ 10% before LVAD implantation. Post-transplant outcomes of interest were acute cellular rejection (ACR), antibody-mediated rejection (AMR), and survival. Results Allosensitization status was evaluated in 268 patients (20% female). Mean age was 52 ± 12 years, and 132 (49.3%) received CF LVADs. After LVAD implant, 30 patients (23%) became newly sensitized, and the level of sensitization appeared to diminish in many of these patients while awaiting transplant. During the study period, 225 of 268 patients underwent transplant, and 43 did not. A CF LVAD was used to bridge 50% of the transplant recipients. Compared with patients without new sensitization or those already sensitized at baseline, the patients with LVAD-associated sensitization had a higher risk of ACR (p = 0.049) and higher risk of AMR (p = 0.018) but a similar intermediate-term post-transplant survival. The patients who did not receive a transplant had higher level of allosensitization, with a baseline cPRA of 20% vs 6% in those who received an allograft and a high risk (40%) of death during follow-up. Conclusions New allosensitization takes place in > 20% of patents supported with CF LVADs. Among patients who undergo transplant, this results in a higher risk of ACR and AMR, but survival remains favorable, likely due to the efficacy of current management after transplant. However, mortality in sensitized patients who do not reach transplant remains high, and new approaches are necessary to meet the needs of this group of patients.

Mechanical cardiovascular support devices are now widely used both in the setting of cardiogenic shock as well as during high risk cardiac catheterization procedures. We report a case of a young female patient who presented with presumed myocarditis and rapidly deteriorating decompensated heart failure requiring the implantation of an Impella Circulatory Support System. Upon transfer to our facility it was discovered that during transport, the Impella device had migrated through the left ventricle. She was emergently taken to the operating room where the Impella was surgically removed and biventricular support devices were placed. The patient eventually expired after weeks of treatment in the intensive care unit. We believe this is the first recorded case of an Impella device perforating the left ventricle. Particularly in cases of newly discovered pericardial effusion, change in waveform on the Impella controller placement signal or rapid decompensation, physicians should consider this rare but potentially catastrophic complication associated with mechanical left ventricular support devices.

Background Outcomes of patients with advanced heart failure (HF) due to restrictive cardiomyopathy (RCM) remain unfavorable in spite of advances in HF therapies. Left ventricular assist devices (LVADs) are a standard therapeutic option for patients with advanced HF, however there is limited data to support LVAD implantation in these patients. The purpose of this study was to examine outcomes in patients with end-stage RCM following LVAD implantation when compared with those with dilated cardiomyopathies (DCM). Methods The International Registry for Mechanically Assisted Circulatory Support (IMACS) registry was queried for all patients with RCM (n = 179) and DCM (n = 15,335) who underwent durable LVAD implantation between January 2013 and September 2017. Patients with RCM were grouped into amyloidosis, sarcoidosis, radiotherapy, idiopathic and other forms of RCM. Baseline patient characteristics, survival, and adverse events were compared among the groups. Results Patients with RCM had a mean age of 56 years and were predominately male (78.9%). Echocardiograms of patients with RCM had significantly smaller left ventricular end-diastolic diameter (LVEDD) compared to DCM (6.3 cm vs 6.8 cm p Conclusions In this analysis of an international registry, we demonstrated that patients with RCM have similar outcomes compared with patients with DCM following LVAD implantation. This observation invites future prospective investigations on validating our findings and on identifying challenges in regards to LVAD implantation in patients with advanced HF due to RCM.

BACKGROUND The new heart allocation system in the United States prioritizes patients supported by temporary mechanical circulatory support (TMCS) devices over those with uncomplicated durable continuous-flow left ventricular assist devices (CF-LVADs), which may increase the number of patients bridged to transplant with TMCS. Limited data are available in guiding post-transplant outcomes with various TMCS devices. We sought to describe post-transplant outcome and identify clinical variables associated with post-transplant outcome in patients bridged to transplant with TMCS. METHODS Using data from the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, we included subjects who underwent transplantation between 2005 and 2016 with known use of mechanical circulatory support. Pre-transplant recipient, donor, and transplant-specific variables were abstracted. The primary outcome was patient survival at 1-year post-transplant. Outcomes of patients bridged to transplant with TMCS were compared with those of patients bridged with CF-LVADs. Cox regression analyses were performed to identify clinical variables associated with the outcomes. RESULTS There were 6,528 patients bridged to transplant with the following types of mechanical circulatory support: durable CF-LVADs (n = 6,206), extracorporeal membrane oxygenation (ECMO, n = 134), percutaneous temporary CF-LVADs (n = 75), surgically implanted temporary CF-LVADs (n = 38) or surgically implanted temporary BiVAD (n = 75). Bridging with ECMO (hazard ratio 3.79, 95% confidence interval [CI] 2.69-5.34, p < 0.001) or percutaneous temporary CF-LVADs (hazard ratio 1.83, 95% CI 1.09-3.08, p = 0.02) was independently associated with higher risk of mortality. Additional risk factors included older donor age, female/male donor-recipient match, older recipient age, higher recipient body mass index, higher recipient creatinine, and prolonged ischemic time. CONCLUSIONS This analysis of a large international cohort of patients bridged to transplant with mechanical circulatory support identified ECMO and percutaneous temporary CF-LVADs as predictors of mortality after transplant, along with additional donor and recipient clinical characteristics. These findings may provide guidance to clinicians in decisions on mechanical circulatory support device selection, transplant eligibility, and timing of transplant.

Gastrointestinal bleeding (GIB) is a leading cause of morbidity during continuous-flow left ventricular assist device (CF-LVAD) support. GIB risk assessment could have important implications for candidate selection, informed consent, and postimplant therapeutic strategies. The aim of the study is to derive and validate a predictive model of GIB in CF-LVAD patients.CF-LVAD recipients at the Utah Transplantation Affiliated Hospitals program between 2004 and 2017 were included. GIB associated with a decrease in hemoglobin ≥2 g/dL was the primary end point. A weighted score comprising preimplant variables independently associated with GIB was derived and internally validated. A total of 351 patients (median age, 59 years; 82% male) were included. After a median of 196 days, GIB occurred in 120 (34%) patients. Independent predictors of GIB included age54 years, history of previous bleeding, coronary artery disease, chronic kidney disease, severe right ventricular dysfunction, mean pulmonary artery pressure18 mm Hg, and fasting glucose107 mg/dL. A weighted score termed Utah bleeding risk score, effectively stratified patients based on their probability of GIB: low (0-1 points) 4.8%, intermediate (2-4) 39.8%, and high risk (5-9) 83.8%. Discrimination was good in the development sample (c-index: 0.83) and after internal bootstrap validation (c-index: 0.74).The novel Utah bleeding risk score is a simple tool that can provide personalized GIB risk estimates in CF-LVAD patients. This scoring system may assist clinicians and investigators in designing tailored risk-based strategies aimed at reducing the burden posed by GIB in the individual CF-LVAD patient and healthcare systems.

Background: Gastrointestinal bleeding (GIB) is a leading cause of morbidity during continuous-flow left ventricular assist device (CF-LVAD) support. GIB risk assessment could have important implications for candidate selection, informed consent, and postimplant therapeutic strategies. The aim of the study is to derive and validate a predictive model of GIB in CF-LVAD patients. Methods and Results: CF-LVAD recipients at the Utah Transplantation Affiliated Hospitals program between 2004 and 2017 were included. GIB associated with a decrease in hemoglobin ≥2 g/dL was the primary end point. A weighted score comprising preimplant variables independently associated with GIB was derived and internally validated. A total of 351 patients (median age, 59 years; 82% male) were included. After a median of 196 days, GIB occurred in 120 (34%) patients. Independent predictors of GIB included age >54 years, history of previous bleeding, coronary artery disease, chronic kidney disease, severe right ventricular dysfunction, mean pulmonary artery pressure 107 mg/dL. A weighted score termed Utah bleeding risk score, effectively stratified patients based on their probability of GIB: low (0–1 points) 4.8%, intermediate (2–4) 39.8%, and high risk (5–9) 83.8%. Discrimination was good in the development sample (c-index: 0.83) and after internal bootstrap validation (c-index: 0.74). Conclusions: The novel Utah bleeding risk score is a simple tool that can provide personalized GIB risk estimates in CF-LVAD patients. This scoring system may assist clinicians and investigators in designing tailored risk-based strategies aimed at reducing the burden posed by GIB in the individual CF-LVAD patient and healthcare systems.

Background: Cardiac allograft vasculopathy (CAV) remains an important source of mortality after heart transplant. The aim of our study was to identify structural and microvasculature changes in severe CAV. Methods and Results: The study group included heart transplant recipients with severe CAV who underwent retransplantation (severe CAV, n=20). Control groups included time from transplant matched cardiac transplant recipients without CAV (transplant control, n=20), severe ischemic cardiomyopathy patients requiring left ventricular assist device implantation (ischemic control, n=18), and normal hearts donated for research (donor control, n=10). We collected baseline demographic information, echocardiography data, and performed histopathologic examination of myocardial microvasculature. Echocardiographic features of severe CAV included lack of eccentric remodeling and presence of significant diastolic dysfunction. In contrast, diastolic function was preserved in transplant control subjects. Histopathologic examination showed increased interstitial fibrosis among severe CAV, transplant controls, and ischemic control patients. Compared with transplant controls, severe CAV subjects had reduced capillary density and increased capillary wall thickness ( P Conclusions: Our results suggest that the marked diastolic dysfunction and resultant symptoms in patients with severe CAV may be secondary to the loss of microvasculature and remodeling of remaining microvessels rather than a consequence of interstitial fibrosis. The clinical significance and potential therapeutic implications of these unique microvasculature characteristics warrant further investigation.

Purpose Revisions to the US heart allocation system are expected to increase the number of patients bridged to transplant with temporary mechanical circulatory support (TMCS). However, the presence of TMCS at time of transplantation can lead to higher risk of post-transplant mortality. We sought to identify clinical variables associated with favorable post-transplant outcome in patients bridged to transplant with TMCS. Methods We examined data in the ISHLT Thoracic Transplant Registry. We included subjects transplanted between 2005 and 2016 with known use of MCS. Pre-transplant recipient, donor and transplant-specific variables were abstracted. The primary outcome was patient survival at 1 year post transplant in patients bridged with various types of MCS. Cox regression analyses were performed to identify predictors of survival and Cox regression coefficients were used to construct a patient survival calculator. Results There were 6,528 patients bridged to transplant with the following types of MCS: continuous flow LVAD (HeartMate II, HeartMate 3, HeartWare, Jarvik 2000; n=6,206), ECMO (n=134), percutaneous temporary LVAD (P-VAD: Impella 2.5, CP, 5.0, TandomHeart; n=75), surgically implanted temporary LVAD (T-LVAD: CentriMag LVAD; n=38) or BiVAD (T-BiVAD: CentriMag BiVAD; n=75). Kaplan Meier survival among the 5 subgroups is shown in Figure 1A. In a multivariable model, bridging with ECMO or P-VAD was associated with higher risk of mortality. Additional risk factors included older donor age, female/male donor-recipient match, older recipient age, higher recipient body mass index and higher recipient creatinine . We created a calculator that quantifies predicted patient survival at 1 year post-transplant based on donor and recipient characteristics at transplant (Figure 1B). Conclusion The calculator is a novel tool to assist providers in refining the selection of transplant candidates with TMCS with the hopes of improving post-transplant outcomes.

Diagnosis, prognosis, treatment, and development of new therapies for diseases or syndromes depend on a reliable means of identifying phenotypes associated with distinct predictive probabilities for these various objectives. Left ventricular ejection fraction (LVEF) provides the current basis for combined functional and structural phenotyping in heart failure by classifying patients as those with heart failure with reduced ejection fraction (HFrEF) and those with heart failure with preserved ejection fraction (HFpEF). Recently the utility of LVEF as the major phenotypic determinant of heart failure has been challenged based on its load dependency and measurement variability. We review the history of the development and adoption of LVEF as a critical measurement of LV function and structure and demonstrate that, in chronic heart failure, load dependency is not an important practical issue, and we provide hemodynamic and molecular biomarker evidence that LVEF is superior or equal to more unwieldy methods of identifying phenotypes of ventricular remodeling. We conclude that, because it reliably measures both left ventricular function and structure, LVEF remains the best current method of assessing pathologic remodeling in heart failure in both individual clinical and multicenter group settings. Because of the present and future importance of left ventricular phenotyping in heart failure, LVEF should be measured by using the most accurate technology and methodologic refinements available, and improved characterization methods should continue to be sought.

Heart failure (HF) in the United States represents a significant burden for patients and a tremendous strain on the healthcare system. Patients receiving a diagnosis of HF can be placed into 1 of 4 New York Heart Association (NYHA) functional classifications; the greatest proportion of patients are in the NYHA class II category, which is defined as patients having a slight limitation of physical activity but who are comfortable at rest, and for whom ordinary physical activity results in symptoms of HF. Because the severity of NYHA class II HF may be perceived as mild or unalarming by this definition, the urgency to treat this type of HF may be overlooked. However, these patients are optimal candidates for active intervention because their HF is at a critical point on the disease progression continuum when untoward changes can be halted or reversed. This review discusses the physiological consequences of NYHA class II HF with reduced ejection fraction and describes recent clinical trials that have demonstrated a therapeutic benefit for patients in this population. In doing so, we hope to establish that patients with NYHA class II disease merit careful attention and to provide reassurance to the treating community that options are available for these patients.

Background In dilated cardiomyopathies (DCMs) changes in expression of protein-coding genes are associated with reverse remodeling, and these changes can be regulated by microRNAs (miRs). We tested the general hypothesis that dynamic changes in myocardial miR expression are predictive of β-blocker-associated reverse remodeling. Methods Forty-three idiopathic DCM patients (mean left ventricular ejection fraction 0.24 ± 0.09) were treated with β-blockers. Serial ventriculography and endomyocardial biopsies were performed at baseline, and after 3 and 12 months of treatment. Changes in RT-PCR (candidate miRs) or array-measured miRs were compared based on the presence (R) or absence (NR) of a reverse-remodeling response, and a miR-mRNA-function pathway analysis (PA) was performed. Results At 3 months, 2 candidate miRs were selectively changed in Rs, decreases in miR-208a-3p and miR-591. PA revealed changes in miR-mRNA interactions predictive of decreased apoptosis and myocardial cell death. At 12 months, 5 miRs exhibited selective changes in Rs (decreases in miR-208a-3p, -208b-3p, 21-5p, and 199a-5p; increase in miR-1-3p). PA predicted decreases in apoptosis, cardiac myocyte cell death, hypertrophy, and heart failure, with increases in contractile and overall cardiac functions. Conclusions In DCMs, myocardial miRs predict the time-dependent reverse-remodeling response to β-blocker treatment, and likely regulate the expression of remodeling-associated miRs. Trial registration ClinicalTrials.gov NCT01798992. Funding NIH 2R01 HL48013, 1R01 HL71118 (Bristow, PI); sponsored research agreements from Glaxo-SmithKline and AstraZeneca (Bristow, PI); NIH P20 HL101435 (Lowes, Port multi-PD/PI); sponsored research agreement from Miragen Therapeutics (Port, PI).

To investigate the biologic relevance of cross-platform concordant changes in gene expression in intact human failing/hypertrophied ventricular myocardium undergoing reverse remodeling.Information is lacking on genes and networks involved in remodeled human LVs, and in the associated investigative best practices.We measured mRNA expression in ventricular septal endomyocardial biopsies from 47 idiopathic dilated cardiomyopathy patients, at baseline and after 3-12 months of β-blocker treatment to effect left ventricular (LV) reverse remodeling as measured by ejection fraction (LVEF). Cross-platform gene expression change concordance was investigated in reverse remodeling Responders (R) and Nonresponders (NR) using 3 platforms (RT-qPCR, microarray, and RNA-Seq) and two cohorts (All 47 subjects (A-S) and a 12 patient "Super-Responder" (S-R) subset of A-S).For 50 prespecified candidate genes, in A-S mRNA expression 2 platform concordance (CcpT), but not single platform change, was directly related to reverse remodeling, indicating CcpT has biologic significance. Candidate genes yielded a CcpT (PCR/microarray) of 62% for Responder vs. Nonresponder (R/NR) change from baseline analysis in A-S, and ranged from 38% to 100% in S-R for PCR/microarray/RNA-Seq 2 platform comparisons. Global gene CcpT measured by microarray/RNA-Seq was less than for candidate genes, in S-R R/NR 17.5% vs. 38% (P = 0.036). For S-R global gene expression changes, both cross-cohort concordance (CccT) and CcpT yielded markedly greater values for an R/NR vs. an R-only analysis (by 22 fold for CccT and 7 fold for CcpT). Pathway analysis of concordant global changes for R/NR in S-R revealed signals for downregulation of multiple phosphoinositide canonical pathways, plus expected evidence of a β1-adrenergic receptor gene network including enhanced Ca2+ signaling.Two-platform concordant change in candidate gene expression is associated with LV biologic effects, and global expression concordant changes are best identified in an R/NR design that can yield novel information.

Objectives Our goal was to identify conventional, deformational, and rotational echocardiographic parameters that could differentiate heart failure patients with preserved ejection fraction secondary to amyloidosis (HFpEF-amyloid) vs. heart failure patients with preserved ejection fraction without amyloidosis (HFpEF). Introduction HFpEF represents a heterogeneous clinical syndrome. Studies have shown that a substantial number of HFpEF patients have cardiac amyloidosis. Early identification of cardiac amyloidosis with a routine imaging modality such as echocardiography could improve disease management and outcomes. Methods and Results Medical records of patients with HFpEF-amyloid and HFpEF were reviewed. The presence of amyloidosis in the HFpEF-amyloid group was confirmed by cardiac biopsy, while cardiac magnetic resonance imaging ruled out its presence in the HFpEF group. The study included 34 patients with HFpEF-amyloid and 33 patients with HFpEF. Conventional echocardiographic parameters were compared between all subjects among the groups, while deformational and rotational parameters were compared between 10 subjects in each group, as these had adequate imaging quality to measure the parameters. Both groups had similar left ventricular ejection fraction. Subjects in the HFpEF-amyloid group had more grade III diastolic dysfunction, a shorter deceleration time, and lower tissue Doppler e’ wave velocities. Patients with HFpEF-amyloid had significantly more impaired left ventricular longitudinal and basal strains and higher relative apical sparing ratios. Conventional echocardiographic parameters with the highest diagnostic accuracy for HFpEF-amyloid were an interventricular septum thickness ≥1.3 cm, a Doppler average e’ ≤6.5 cm/sec, a septal e’ 0.8. For deformational parameters, a relative apical sparing strain ratio of ≥1.5 and a basal longitudinal strain ≥-12% showed the highest accuracy to diagnose HFpEF-amyloid with AUC of 0.98 and 0.96, respectively (Table). Conclusion In patients with HFpEF, specific conventional and deformational echocardiographic parameters could reveal patterns for earlier identification of cardiac amyloidosis.

Purpose Predicting cardiac recovery (CR) in advanced heart failure (HF) patients before left ventricular assist device (LVAD) implantation remains challenging. This study sought to investigate whether CR after LVAD unloading can be predicted by cardiac functional and structural parameters together with clinical characteristics. Methods From 2008 to 2016, consecutive advanced chronic HF patients (N=347) supported with durable continuous-flow LVADs were prospectively evaluated. Patients with acute HF etiologies or without adequate post-LVAD follow up ( Results CR occurred in 13.7% of patients. Univariate analysis showed that responders were more likely to be young, female, non-ischemic cardiomyopathy, with shorter HF symptoms duration and no prior heart surgery. They had lower blood urea nitrogen and were less likely to be on temporary mechanical support before LVAD. The multivariable UCAR model (AUC=0.755; p Conclusion Univariate and multivariable predictors of CR include both modifiable and non-modifiable patient characteristics that are known prior to LVAD implantation. The UCAR score can serve as a practical tool for targeted patient selection to implement protocols that facilitate CR in the advanced HF patient subpopulation that is most likely to respond.

Objectives This study sought to prospectively investigate the longitudinal effects of continuous-flow left ventricular assist device (LVAD) unloading on myocardial structure and systolic and diastolic function. Background The magnitude, timeline, and sustainability of changes induced by continuous-flow LVAD on the structure and function of the failing human heart are unknown. Methods Eighty consecutive patients with clinical characteristics consistent with chronic heart failure requiring implantation of a continuous-flow LVAD were prospectively enrolled. Serial echocardiograms (at 1, 2, 3, 4, 6, 9, and 12 months) and right heart catheterizations were performed after LVAD implant. Cardiac recovery was assessed on the basis of improvement in systolic and diastolic function indices on echocardiography that were sustained during LVAD turn-down studies. Results After 6 months of LVAD unloading, 34% of patients had a relative LV ejection fraction increase above 50% and 19% of patients, both ischemic and nonischemic, achieved an LV ejection fraction ≥40%. LV systolic function improved as early as 30 days, the greatest degree of improvement was achieved by 6 months of mechanical unloading and persisted over the 1-year follow up. LV diastolic function parameters also improved as early as 30 days after LVAD unloading, and this improvement persisted over time. LV end-diastolic and end-systolic volumes decreased as early as 30 days after LVAD unloading (113 vs. 77 ml/m2, p Conclusions Continuous-flow LVAD unloading induced in a subset of patients, both ischemic and nonischemic, early improvement in myocardial structure and systolic and diastolic function that was largely completed within 6 months, with no evidence of subsequent regression.

Background Rejection, cardiac allograft vasculopathy (CAV), and infection are significant causes of mortality in heart transplantation recipients. Assessing the immune status of a particular patient remains challenging. Although endomyocardial biopsy (EMB) and angiography are effective for the identification of rejection and CAV, respectively, these are expensive, invasive, and may have numerous complications. The aim of this study was to evaluate the immune function and assess its utility in predicting rejection, CAV, and infection in heart transplantation recipients. Methods We prospectively obtained samples at the time of routine EMB and when clinically indicated for measurement of the ImmuKnow assay (IM), 12 cytokines and soluble CD30 (sCD30). EMB specimens were evaluated for acute cellular rejection, and antibody-mediated rejection (AMR). CAV was diagnosed by the development of angiographic coronary artery disease. Infectious episodes occurring during the next 30 days after testing were identified by the presence of positive bacterial or fungal cultures and/or viremia that prompted treatment with antimicrobials. Results We collected 162 samples from 56 cardiac transplant recipients. There were 31 infection episodes, 7 AMR, and 4 CAV cases. The average IM value was significantly lower during infection, ( P = .04). Soluble CD30 concentrations showed significantly positive correlation with infection episodes, ( P = .001). Significant positive correlation was observed between interleukin-5(IL-5) and AMR episodes ( P = .008). Tumor necrosis factor–α and IL-8 showed significant positive correlation with CAV ( P = .001). Conclusions Immune function monitoring appears promising in predicting rejection, CAV, and infection in cardiac transplantation recipients. This approach may help in more individualized immunosuppression and it may also minimize unnecessary EMBs and cardiac angiographies.

We present the case of two patients with idiopathic dilated cardiomyopathy and moderate aortic valve regurgitation that were treated with a bioprosthetic valve at the time of the left ventricular assist device (LVAD) implantation. A few months later, patients revealed partial recovery in the left ventricle systolic function. Both patients, during the LVAD turndown protocol, reported the onset of chest pain. The transthoracic echocardiography revealed the presence of a new transaortic pressure gradient. We confirmed the presence of a fused bioprosthetic valve by further performing a transesophageal echocardiogram and a left and right heart catheterization. Replacement of aortic valve at the time of an LVAD implantation constitutes a challenging case. Although a mechanical valve is contraindicated due to the increased thromboembolic risk, selecting a bioprosthetic valve increases the risk of valve leaflets fusion. The consequences of this phenomenon should be acknowledged in LVAD patients undergoing aortic valve replacement with a bioprosthetic, especially under the view of LVAD explantation for those revealing myocardial recovery under mechanical unloading.

Antibody-mediated rejection (AMR) of cardiac allografts is associated with reduced long-term graft survival, but not every patient with AMR develops premature graft failure. The tissue level mechanisms leading to graft failure in some patients with antibody-mediated rejection are poorly characterized.We assessed changes in myocardial microvessel density (number of capillaries per unit area) in endomyocardial biopsies over time using whole-slide microscopic imaging of CD34-stained slides and computer-assisted image analysis. Changes were compared among eight heart transplant recipients with multiple episodes of pathologic AMR who died from cardiovascular causes, eight age- and gender-matched patients with pathologic AMR who were still alive at a similar follow-up interval, and six matched controls without AMR or cellular rejection.Microvessel density decreased in the last biopsies (mean 6.52 years post-transplant) from patients with pathologic AMR and cardiovascular mortality compared to their biopsies at 6 and 12 months post-transplant [respectively, -22% (P=.02) and -25% (P=.02)]. A similar decrease was not seen for the other groups.Significantly reduced myocardial microvessel density does occur in a subset of patients with pathologic AMR who have a worse outcome. These data provide insights into the interplay between AMR, microvascular injury, and clinical outcomes.

Background Growing evidence suggests worse cardiac allograft vasculopathy and mortality in patients with asymptomatic antibody-mediated rejection (AMR). Debate continues about whether therapeutic intervention is warranted to avoid adverse outcomes. In this study we examine the course of individual episodes of untreated asymptomatic AMR on follow-up endomyocardial biopsy (EMB). Methods The U.T.A.H. Cardiac Transplant Program database was queried for transplant recipients between 1985 and 2009 who survived beyond 1 year and had at least 1 episode of lone AMR with a follow-up EMB. All EMBs were screened for AMR by immunofluorescence and graded for severity. Data were analyzed based on time from transplant (early, ≤12 months; late, >12 months). Results Nine hundred fifty-eight patients with a total of 15,448 biopsies qualified for the study. Average age at transplant was 46.7 years; 13% of the patients were female. Within the first year post-transplant, asymptomatic AMR was diagnosed in 13.6% of biopsies compared with 5.2% beyond 1 year. AMR resolved in 65% (early) vs 75% (late) on follow-up EMB. More severe AMR was less likely to improve regardless of time from transplant. Furthermore, after an episode of AMR had resolved, the recurrence rate at 3, 6 and 12 months was 44%, 50.1% and 56.2%, respectively. Conclusions The incidence of AMR is higher in the first year post-transplant and the likelihood of resolution is less on follow-up EMB, especially when more severe. A small but significant number of cases became worse or did not change. These new findings may be helpful in planning future studies that test whether therapeutic interventions on asymptomatic AMR favorably impact outcomes.

β-Adrenergic receptors (β-AR) are central to the overall regulation of cardiac function. From the first proposed receptor/transmitter concept to the latest clinical β-blocker trials β-AR have been shown to play an important role in cardiac disease and heart failure in particular. This study provides a historical perspective, reviews the latest discoveries and beliefs, and discusses the current clinical practices of β-AR and their modulation with their associated guanine-nucleotide regulatory protein/adenylylcyclasesignal transduction pathways.

Chronic kidney disease continues to be a major limiting factor for long-term survival of heart transplant recipients. Little is known about the early use of renin-angiotensin system (RAS) blocking agents and their impact on renal function and hemodynamics in heart transplant recipients. In this cohort study all eligible recipients of orthotopic heart transplants at the UTAH cardiac transplantation program from 2001 through 2007 were divided into 2 groups-patients who were started on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers within the first 4 weeks of transplantation and continued on these for ≥4 weeks during the first 3 months (RAS blockade group, n = 75) and those who were not (non-RAS blockade group, n = 52). All patients were followed for 1 year after transplantation. There were no significant differences at baseline between the 2 groups. Estimated glomerular filtration rate at 12 months was significantly higher in the RAS blockade group compared to the non-RAS blockade group (mean ± SD, 56.3 ± 22.4 vs 47.3 ± 18.1 ml/min/1.73 m(2), p = 0.036). At 12 months pulmonary artery systolic pressure was significantly lower in the RAS blockade group compared to the non-RAS blockade group (30.2 ± 7.4 vs 32.9 ± 9.3 mm Hg, p = 0.023). Left ventricular ejection fraction and pulmonary capillary wedge pressure were similar between the 2 groups. In conclusion, early RAS blockade after heart transplantation is safe, well tolerated, and associated with better renal function and hemodynamic profile at 1 year after transplantation.

Left ventricular hypertrophy (LVH) of the donor heart is believed to increase the risk of allograft failure after transplant. However this effect is not well quantified, with variable findings from single-center studies. The United Network for Organ Sharing database was used to analyze the effect of donor LVH on recipient survival. Three cohorts, selected in accordance with the American Society of Echocardiography guidelines, were examined: recipients of allografts without LVH (55 years, and in recipients of allografts with LVH and ischemic time ≥4 h. In the contemporary era, close to half of all transplanted allografts demonstrate LVH, and survival of these recipients is similar to those without LVH. However, the use of allografts with LVH in association with other high-risk characteristics may result in increased mortality.

To better characterize the contribution of both central and peripheral mechanisms to passive limb movement-induced hyperemia, we studied nine recent (

Few data exist on the safety of transferring patients to standard oral therapy for chronic heart failure (CHF) after acute management with inotropic agents. This study compares hemodynamic responses and cardiac dysrhythmic effects of continuous infusion of enoximone, dobutamine, or placebo in patients with moderate to severe CHF. The authors enrolled 136 patients who were randomly assigned to either open-label dobutamine or double-blind enoximone vs placebo. After 24 hours of treatment, the study was unblinded. Patients receiving placebo completed the study. Patients receiving enoximone or dobutamine received the infusion for an additional 24 hours and were then switched to standard oral therapy for 72 hours. Compared with placebo, both enoximone and dobutamine increased cardiac index and decreased pulmonary capillary wedge pressure (PCWP). Compared with dobutamine, enoximone significantly increased cardiac index after the first 24 hours of infusion and significantly decreased PCWP throughout the infusion period. There was no difference in the incidence of arrhythmias between enoximone and dobutamine. More patients (65%) tolerated the switch to oral therapy in the enoximone group compared with dobutamine (49%; P =.12). Enoximone is effective in improving the hemodynamics in patients with moderate to severe CHF and is tolerated at least as well as dobutamine. Congest Heart Fail. 2010;16:265–270. © 2010 Wiley Periodicals, Inc.

Hyponatremia is a common electrolyte disorder in patients with heart failure (HF) associated with cognitive dysfunction and increased mortality and rehospitalization rates. Loop diuretics worsen renal function, produce neurohormonal activation, and induce electrolyte imbalances. Lixivaptan is a selective, oral vasopressin V2‐receptor antagonist that improves hyponatremia by promoting electrolyte‐free aquaresis without significant side effects. The Treatment of Hyponatremia Based on Lixivaptan in NYHA Class III/IV Cardiac Patient Evaluation (BALANCE) study is a randomized, double‐blind, placebo‐controlled, phase 3 trial designed to evaluate the effects of lixivaptan on serum sodium in patients hospitalized with worsening heart failure (target N= 650), signs of congestion and serum sodium concentrations

Background Blood product transfusion has been successfully used in solid-organ transplantation to induce tolerance. Whether a similar protective effect of blood product transfusion exists in heart transplantation is controversial. Objective To investigate the effect of cellular blood product transfusion within 2 weeks posttransplantation on the incidence of cellular and antibody-mediated rejection. Patients and Methods Patients were grouped on the basis of number of blood transfusions; group 1 received no transfusions, and groups 2, 3, and 4 each received an incremental number of transfusion units. All endomyocardial biopsy samples were routinely studied using immunofluorescence in the first 12 weeks posttransplantation. Results Baseline characteristics including age, sex, body mass index, history of diabetes, donor characteristics, and pretransplantation laboratory values were similar except that group 4 had a higher rate of previous sternotomy and longer ischemic time during transplantation. Approximately 9200 endomyocardial biopsy samples composed the data. Short- and long-term freedom from the International Society for Heart & Lung Transplantation grade 3A or higher cellular rejection and from antibody-mediated rejection were comparable between groups. Conclusions Blood transfusions within the first 2 weeks post-transplantation do not seem to confer any protective effect against posttransplantation cellular rejection or antibody- mediated rejection. Whether other unmeasured confounding factors mask their effect requires further prospective studies.

Introduction We aim to evaluate trends in patient characteristics, causes of hospitalization, procedure utilization, and outcomes in hypertrophic cardiomyopathy (HCM) patients. Methods Data from the Nationwide Inpatient Sample database (NIS) were analyzed to identify all patients who had secondary diagnosis of HCM from 2007-2014. Results We identified 139,342 HCM admissions from 2007 to 2014 (mean age 66±16 years, 62% female and 75% Caucasian). There was no significant difference in nationwide trends in regard to the number of admissions. The most common reason for hospitalizations were: acute heart failure (47%), atrial fibrillation (16%), cerebrovascular accident (2%), syncope (1.5%) ventricular tachycardia (1%), and ventricular fibrillation or sudden cardiac death (VF/SCD) (0.3%) ( Table 1 ). In regard to interventions, 659 (0.47%) patients underwent alcohol septal ablation, 4790 (3.44%) underwent septal myomectomy, 659 (0.47%) underwent ablation for atrial fibrillation, 99 (0.07%) underwent ventricular tachycardia ablation, 4931 (3.54%) underwent implantable cardiac defibrillator (ICD) implantation, and 3823 (2.74%) underwent mitral valve replacement (MVR) ( Table-2 ). Overall in-hospital mortality was 3%. There was a significant trend towards lower all-cause mortality from 2007 to 2014 (3.43% Vs 2.74% respectively; P trend Conclusion AHF is the most common reason for admission among HCM patients. While there is a trend towards lower mortality in recent years, HCM patients admitted for VF/SCD and CVA have the highest mortality. Despite female patients with HCM being more likely to be hospitalized, they are less likely to undergo interventions.

Background We hypothesize that early right heart catheterization (RHC)/pulmonary artery catheter (PAC) placement in cardiogenic shock (CS) patients may allow to better target treatment, reduce length of stay (LOC), in-hospital mortality and readmission rates. Methods Using the National Readmission Database (NRD) we identified CS index admissions, in-hospital mortality, LOC and 30-day readmissions between January and November of 2014. The utilization and timing of RHC/PAC and its influence on in-hospital mortality, LOC and 30-day readmission rates were analyzed. Results A total of 11591 index CS hospital admissions were identified (mean age 62.7 ±15 years; females 32.6%). The overall in-hospital mortality among the CS patients was 27% and median LOC was 13.0 [8.0, 21.0] days. 3487 (33%) patients had readmissions within 30 days (30%; females). During the index hospitalization, 3390 (30%) CS patients underwent RHC/PAC. More men and young patients underwent RHC/PAC (71% Vs. 66% and 57.5±14.4 years Vs. 65.2±15 years respectively; P Conclusions Among the patients admitted with CS, utilization of RHC/PAC may reduce the mortality rates. Furthermore, those who receive early (

Background There is increasing recognition that female patients supported by continuous flow left ventricular assist devices (CF-LVADs) have worse outcome in terms of overall survival and adverse events. However, reports on sex differences in risk of pump thrombosis have been inconclusive. Objective Our aim was to evaluate the association between sex and the risk of pump thrombosis. Methods We included patients receiving a CF-LVAD at our institution from 2007 to 2017. The primary endpoint was time to first pump thrombosis during 3 years of follow up. The Kaplan-Meier method was used to analyze survival free of pump thrombosis based on sex and Cox regression was used to determine the predictors of pump thrombosis. Results Our cohort included 301 patients (median age 59), of which 49 (16.3%) were female. During a median follow up time of 846 (interquartile range 313-1096) days, 31 (10.3%) patients developed pump thrombosis. Survival free of pump thrombosis was lower in female patients ( figure 1 ). After adjusting for covariates (including age, race, body mass index, heart failure etiology, LVAD types, LVAD designations and medical comorbidities), the risk of pump thrombosis was higher for female patients than male patients (hazard ratio 2.64, 95% confidence interval 1.22-5.69, p= 0.01). Conclusion The risk of pump thrombosis following LVAD varies based on sex, with female patients at higher risk. Further research is warranted to fully understand these differences, and whether device management strategies should be tailored based on sex.

Background In a subset of patients with heart failure with reduced ejection fraction (HFrEF) disease modifying therapy results in improvement of left ventricular EF (HFiEF). Yet, it has been noted that HFiEF patients may experience clinical events exceeding that of a healthy population. Our aim was to examine health-related quality of life (hrQOL) in HFiEF and compare it to those with HFrEF and HF with preserved ejection fraction (HFpEF). Methods In a large HF clinic, hrQOL was routinely assessed using the disease-specific 12-question Kansas City Cardiomyopathy Questionnaire (KCCQ-12), the visual analogue scale (VAS) and the Patient-Reported Outcomes Measurement Information System (PROMIS) scale in the domains of physical function, fatigue, depression, and satisfaction with social roles and activities. HFrEF was defined as LVEF Results The study population consisted of 1,337 patients, average age was 59±16.6 years and 65% were male. The demographics of patients in the three groups of interest - HFiEF (N=181), HFrEF (N=878) and HFpEF (n=318) are shown in Table 1 . Compared to HFrEF and HFpEF, patients with HFiEF had better scores for KCCQ, PROMIS physical function and fatigue (p Figure 1 . HFiEF also had better score for VAS compared to HFrEF (p=0.002). There were no significant differences between scores for PROMIS depression and satisfaction with social roles among the three groups (p=NS). Despite the overall better hrQOL profile, HFiEF PROMIS scores remained below the population median. Summary Our results indicate that HFiEF patients have overall better hrQOL than patients with HFrEF and HFpEF. However, their hrQOL remains below that of the general population. More study is needed to determine the causes of these limitations and ways to further improve hrQOL in HFiEF patients.

Background In the absence of robust evidence from randomized controlled trials, clinicians treating cardiogenic shock (CS) often make decisions on short-term Mechanical Circulatory Support (s-t MCS) based on individual center or clinical team preferences. We sought to investigate whether description of device-related adverse events (AE) could help identify targets to advance the field. Methods Our institution's CS database was queried for CS patients who underwent placement of s-t MCS based on predefined criteria, between Jan 2014 - Mar 2017. Patients who needed Intra-Aortic Balloon Pump, central cannulation or had a post-cardiotomy CS were excluded from the analysis. We identified 61 who required s-t MCS with Impella, peripheral Veno-Arterial Extra-Corporeal Membrane Oxygenation (VA-ECMO) or combination of these devices as a sequela of escalating support strategy. Results Of the total patients, 23 (37.7%) were treated with Impella, 10 (16.4%) with VA-ECMO and the remaining 28 (45.9%) with combinations of devices. Groups were of similar demographics and CS etiology. Severity of CS pre-MCS revealed no differences in vital signs, number of vasoactive agents used, left ventricular ejection fraction, use of mechanical ventilation and CPR. The VA-ECMO compared with Impella and Combination groups had higher baseline lactate (11.1 vs 4.9 vs 5.3; p=0.002) and lower baseline pH (7.05 vs 7.27 vs 7.27; p=0.004) pre-MCS. The mean length of support was similar between Impella and VA-ECMO groups, however it was longer in the Combination vs Impella group (p=0.001). Major AE are shown in the Table . The mean ICU stay was 15 days and did not differ among the groups. Exchange to durable LVAD was performed in 6 patients: 3/23 (Impella) and 3/28 (Combination) group. The overall survival to hospital discharge was 43% and did not differ between the groups (p=0.2). Conclusions Despite significant advances in the technology of s-t MCS options, morbidity and mortality remain high and the device-related AE could provide practical quality improvement targets for CS programs.