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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: Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed “responders”). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown. Methods: To identify changes in signaling pathways operative in the normal and failing human heart and to molecularly characterize patients who respond favorably to LVAD unloading, we performed global RNA sequencing and phosphopeptide profiling of left ventricular tissue from 93 patients with HF undergoing LVAD implantation (25 responders and 68 nonresponders) and 12 nonfailing donor hearts. Patients were prospectively monitored through echocardiography to characterize their myocardial structure and function and identify responders and nonresponders. Results: These analyses identified 1341 transcripts and 288 phosphopeptides that are differentially regulated in cardiac tissue from nonfailing control samples and patients with HF. In addition, these unbiased molecular profiles identified a unique signature of 29 transcripts and 93 phosphopeptides in patients with HF that distinguished responders after LVAD unloading. Further analyses of these macromolecules highlighted differential regulation in 2 key pathways: cell cycle regulation and extracellular matrix/focal adhesions. Conclusions: This is the first study to characterize changes in the nonfailing and failing human heart by integrating multiple -omics platforms to identify molecular indices defining patients capable of myocardial recovery. These findings may guide patient selection for advanced HF therapies and identify new HF therapeutic targets.

Objective To identify predictors of 30-day all-cause mortality for patients with cardiogenic shock secondary to acute coronary syndrome (ACS-CS) who require short-term mechanical circulatory support (ST-MCS). Background ACS-CS mortality is high. ST-MCS is an attractive treatment option for hemodynamic support and stabilization of deteriorating patients. Mortality prediction modeling for ACS-CS patients requiring ST-MCS has not been well-defined. Methods The Utah Cardiac Recovery (UCAR) Shock database was used to identify patients admitted with ACS-CS requiring ST-MCS devices between May 2008 and August 2018. Pre-ST-MCS clinical, laboratory, echocardiographic, and angiographic data were collected. The primary endpoint was 30-day all-cause mortality. A weighted score comprising of pre-ST-MCS variables independently associated with 30-day all-cause mortality was derived and internally validated. Results A total of 159 patients (mean age, 61 years; 78% male) were included. Thirty-day all-cause mortality was 49%. Multivariable analysis resulted in four independent predictors of 30-day all-cause mortality: age, lactate, SCAI CS classification, and acute kidney injury. The model had good calibration and discrimination (area under the receiver operating characteristics curve 0.80). A predictive score (ranging 0-4) comprised of age ≥ 60 years, pre-ST-MCS lactate ≥2.5 mmol/L, AKI at time of ST-MCS implementation, and SCAI CS stage E effectively risk stratified our patient population. Conclusion The ACS-MCS score is a simple and practical predictive score to risk-stratify CS secondary to ACS patients based on their mortality risk. Effective mortality risk assessment for ACS-CS patients could have implications on patient selection for available therapeutic strategy options.

A growing proportion of transplant donors and recipients have a history of COVID-19 infection. This study sought to characterize clinical practice after recipient or donor COVID-19 infection.An online survey was distributed to heart transplant clinicians through a professional society message board and social media. Responses were collected between September 29 and November 5, 2021.There were 222 health care professionals (68% transplant cardiologists, 22% transplant surgeons, 10% other) across diverse geographic regions who completed the survey. While there was significant variation in donor acceptance, as it relates to past and current COVID-19 infection, the respondents were fairly cautious: 28% would not typically accept a donor with a history of COVID-19 regardless of the infection course and 80% would not accept donors who had evidence of myocardial dysfunction during past COVID-19 infection, or who died of COVID-19 or its complications. The timing of candidate reactivation on the waiting list after COVID-19 infection also varied and often diverged from scenarios addressed by social guidelines. Eighty-one percent of the respondents felt COVID-19 vaccine should be mandatory before transplant, but this rate varied by geographic region.Our results reflect evolving experience of the heart transplant field at a time of lack of high-quality evidence. In the absence of longer-term outcome data for donors and transplant candidates with history of COVID-19 infection, clinicians remain cautious; however, this approach will likely need to be refined as an increasing proportion of the population will continue to be infected with COVID-19.

Background Studies have indicated differences between Asians and Whites in their propensity for stroke, coronary artery disease, heart failure, bleeding and thrombosis. We investigated whether Asian-Americans on durable left ventricular assist devices (LVADs) exhibit differential morbidity and mortality when compared to Whites. Methods We analysed prospectively collected data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database to compare the outcomes after LVAD implantation of Asians versus Whites. Results In total, 7,018 patients were included, 130 were identified as Asian-Americans. Asian-Americans were younger, had lower body mass index, higher serum bilirubin and lower albumin levels. In a multivariable regression model, there was no difference in survival between the two groups. Asian-Americans had lower incidence of device malfunction and after adjusting for multiple factors this remained lower. The adjusted risk of a major safety composite outcome, including major bleeding, major infection, stroke and device malfunction, revealed no difference between the two groups. Conclusions Although prior studies have reported worse cardiac surgery outcomes in Asians, in this INTERMACS analysis Asian-Americans appear to have similar survival and risk of adverse events as their White counterparts. The incidence of device malfunction was lower in the Asian-Americans, both in a univariate model and after adjusting for multiple clinical factors. Future, larger studies of Asian-Americans with end-stage heart failure and LVAD support are warranted to confirm these results.

Background Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering t...

Objective: To describe the structural sequelae of carbon monoxide (CO) poisoning on the heart assessed using stress cardiac MRI (CMR). CO poisoning is common. While acute cardiac injury is frequent among survivors, the mid- and long-term effects of CO on the myocardium are unclear. Methods: CMR studies performed between the years 2005 and 2014 for a primary diagnosis of CO poisoning at a tertiary care center were reviewed by an experienced cardiologist. Variables of interest were compared between patients with normal and abnormal studies to identify factors associated with cardiac dysfunction. Results: Eighty-eight patients underwent stress CMR, age 34 years (range 11-70); 49% were male, 74 had acute poisoning and 14 had chronic poisoning (CO exposure for longer than 24 hours). Time from CO poisoning to imaging was 24 months (1day-120 months). Patients were stratified into four categories, which included those with acute poisoning imaged: • ≤12 months; • 12-60 months; • >60 months from the event; and • those with chronic poisoning. Overall, 26 studies (30%) were abnormal. The most common findings were: left ventricular systolic dysfunction in 14 patients, right ventricular systolic dysfunction in nine, and LV dilatation in six. Abnormalities were mild in most cases and were equally prevalent in all four patient categories. Dyspnea at the time of follow-up was more frequent among those with abnormal studies. Conclusions: Mild alterations in ventricular structure and function are frequent in survivors of CO poisoning. Myocardial scarring is rare, suggesting that acute hypoxic injury may not fully explain these abnormalities.

Cardiac remodeling is an adaptive, compensatory biological process following an initial insult to the myocardium that gradually becomes maladaptive and causes clinical deterioration and chronic heart failure (HF). This biological process involves several pathophysiological adaptations at the genetic, molecular, cellular, and tissue levels. A growing body of clinical and translational investigations demonstrated that cardiac remodeling and chronic HF does not invariably result in a static, end-stage phenotype but can be at least partially reversed. One of the paradigms which shed some additional light on the breadth and limits of myocardial elasticity and plasticity is long term mechanical circulatory support (MCS) in advanced HF pediatric and adult patients. MCS by providing (a) ventricular mechanical unloading and (b) effective hemodynamic support to the periphery results in functional, structural, cellular and molecular changes, known as cardiac reverse remodeling. Herein, we analyze and synthesize the advances in our understanding of the biology of MCS-mediated reverse remodeling and myocardial recovery. The MCS investigational setting offers access to human tissue, providing an unparalleled opportunity in cardiovascular medicine to perform in-depth characterizations of myocardial biology and the associated molecular, cellular, and structural recovery signatures. These human tissue findings have triggered and effectively fueled a "bedside to bench and back" approach through a variety of knockout, inhibition or overexpression mechanistic investigations in vitro and in vivo using small animal models. These follow-up translational and basic science studies leveraging human tissue findings have unveiled mechanistic myocardial recovery pathways which are currently undergoing further testing for potential therapeutic drug development. Essentially, the field is advancing by extending the lessons learned from the MCS cardiac recovery investigational setting to develop therapies applicable to the greater, not end-stage, HF population. This review article focuses on the biological aspects of the MCS-mediated myocardial recovery and together with its companion review article, focused on the clinical aspects, they aim to provide a useful framework for clinicians and investigators.

Introduction: Accurate assessment of the risk of adverse outcomes can assist in the management of patients with heart failure (HF). Hypothesis: Health-related quality of life (HRQoL) can improve prediction of HF outcomes beyond that of the more traditional clinical disease characteristics. Methods: We included consecutive patients with HF with reduced ejection fraction (HFrEF) who were seen in the HF clinic and completed patient reported outcome assessment (PROs) as part of routine care. Elastic net and gradient boosting regression analysis were used to build predictive models for HF hospitalization, heart transplant, left ventricular assist device implantation or death (composite outcome), including a range of clinical variables and PRO results as covariates. Results: There were 1,165 patients with HFrEF (mean age 60.5±16.2, 65% male) with median follow-up time of 490 days. Addition of PROs to more traditional risk factors improved model performance, as analyzed by C-statistics. The gradient boosting regression was chosen as the final model based on superior prediction performance - c-statistic 0.733 and favorable stratification of patient risk - Figure 1A . The Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ) and PROMIS dimensions of Satisfaction with social roles and activities and Physical function were covariates with high variable importance measure in the model. The predictive value of PROs was also confirmed by determining freedom from the composite endpoint in the 20th, 50th and 80th percentiles of PRO strata, while assigning the remaining clinical variables a median value ( Figure 1B ). In this analysis, PROs discriminated outcomes independent of other clinical characteristics. Conclusions: HRQoL appears to significantly modify outcome in HFrEF. Routine assessment of PROs could help to more accurately assess risk of adverse outcomes and personalize informed treatment decisions.

Background Cardiogenic shock from most causes has unfavorable prognosis. Hypertrophic cardiomyopathy (HCM) can uncommonly present with apical ballooning and shock in association with sudden development of severe and unrelenting left ventricular (LV) outflow obstruction. Typical HCM phenotypic features of mild septal thickening, outflow gradients, and distinctive mitral abnormalities differentiate these patients from others with Takotsubo syndrome, who have normal mitral valves and no outflow obstruction. Methods and Results We analyzed 8 patients from our 4 HCM centers with obstructive HCM and abrupt presentation of cardiogenic shock with LV ballooning, and 6 cases reported in literature. Of 14 patients, 10 (71%) were women, aged 66±9 years, presenting with acute symptoms: LV ballooning; depressed ejection fraction (25±5%); refractory systemic hypotension; marked LV outflow tract obstruction (peak gradient, 94±28 mm Hg); and elevated troponin, but absence of atherosclerotic coronary disease. Shock was managed with intravenous administration of phenylephrine (n=6), norepinephrine (n=6), β‐blocker (n=7), and vasopressin (n=1). Mechanical circulatory support was required in 8, including intra‐aortic balloon pump (n=4), venoarterial extracorporeal membrane oxygenation (n=3), and Impella and Tandem Heart in 1 each. In refractory shock, urgent relief of obstruction by myectomy was performed in 5, and alcohol ablation in 1. All patients survived their critical illness, with full recovery of systolic function. Conclusions When cardiogenic shock and LV ballooning occur in obstructive HCM, they are marked by distinctive anatomic and physiologic features. Relief of obstruction with targeted pharmacotherapy, mechanical circulatory support, and myectomy, when necessary for refractory shock, may lead to survival and normalization of systolic function.

Endomyocardial biopsy (EMB), the reference surveillance test for acute rejection (AR) in heart transplant (HTx) recipients, is invasive, costly, and shows significant interobserver variability. Recent studies indicate that donor-derived cell-free DNA (dd-cfDNA), obtained non-invasively from blood, is associated with AR and could reduce the frequency of EMB surveillance. The aim of this study was to examine the performance characteristics of a novel test for detecting AR in adult HTx recipients.Plasma samples with contemporaneous EMBs were obtained from HTx recipients. A clinically available SNP-based massively multiplexed-PCR dd-cfDNA assay was used to measure dd-cfDNA fraction. dd-cfDNA fractions were compared with EMB-defined rejection status and test performance was assessed by constructing ROC curves and calculating accuracy measures.A total of 811 samples from 223 patients with dd-cfDNA testing and contemporaneous EMB were eligible for the study. dd-cfDNA fraction was significantly higher in AR (median 0.58%, IQR, 0.13%-1.68%) compared to non-AR (median 0.04%, IQR, 0.01%-0.11%, pThis novel dd-cfDNA test detects AR in HTx recipients with good accuracy and holds promise as a noninvasive test for AR in HTx recipients.

The 2018 U.S. heart allocation system offers an accelerated pathway for heart transplantation to the most urgent patients.This study sought to determine whether the new allocation system resulted in lower likelihood of candidate recovery.Adult patients waitlisted for heart transplantation with temporary mechanical circulatory support at the time of initial listing between 2010 and 2020 in the United Network for Organ Sharing registry were included. Competing events of heart transplantation, waitlist death or delisting for deteriorating condition, and delisting for improved condition (candidate recovery) were analyzed in the new vs old heart allocation system.A total of 688 patients were waitlisted with venoarterial extracorporeal membrane oxygenation or a surgical nondischargeable biventricular assist device (status 1 or old 1A). Overall, 2,237 patients were waitlisted with an intra-aortic balloon pump, a percutaneous left ventricular assist device (LVAD), or a surgical nondischargeable LVAD (status 2 or old 1A). Patients waitlisted with venoarterial extracorporeal membrane oxygenation or a nondischargeable biventricular assist device had significantly shorter median waitlist times (5 vs 31 days), higher incidence for cardiac transplantation (81.5% vs 43.0%), and lower incidence of candidate recovery (1.5% vs 7.9%) in the new vs old heart allocation system (all P 0.05). Patients waitlisted with an intra-aortic balloon pump or percutaneous or a nondischargeable LVAD also had significantly shorter median waitlist times (8 vs 35 days), higher incidence of transplantation (88.9% vs 64.9%), and lower incidence of candidate recovery (0.2% vs 1.6%) in the new vs old heart allocation system (all P 0.05).Current practice of the new allocation system may not offer select temporary mechanical circulatory support patients the opportunity and adequate time to recover to the point of waitlist removal. Further research will determine which patients would benefit from urgent transplantation vs recovery strategy.

Heart failure (HF) is a leading cause of morbidity and mortality in the United States and worldwide. As a multifactorial syndrome with unpredictable clinical outcomes, identifying the common molecular underpinnings that drive HF pathogenesis remains a major focus of investigation. Disruption of cardiac gene expression has been shown to mediate a common final cascade of pathological hallmarks wherein the heart reactivates numerous developmental pathways. Although the central regulatory mechanisms that drive this cardiac transcriptional reprogramming remain unknown, epigenetic contributions are likely. In the current study, we examined whether the epigenome, specifically DNA methylation, is reprogrammed in HF to potentiate a pathological shift in cardiac gene expression. To accomplish this, we used paired-end whole genome bisulfite sequencing and next-generation RNA sequencing of left ventricle tissue obtained from seven patients with end-stage HF and three nonfailing donor hearts. We found that differential methylation was localized to promoter-associated cytosine-phosphate-guanine islands, which are established regulatory regions of downstream genes. Hypermethylated promoters were associated with genes involved in oxidative metabolism, whereas promoter hypomethylation enriched glycolytic pathways. Overexpression of plasmid-derived DNA methyltransferase 3A in vitro was sufficient to lower the expression of numerous oxidative metabolic genes in H9c2 rat cardiomyoblasts, further supporting the importance of epigenetic factors in the regulation of cardiac metabolism. Last, we identified binding-site competition via hypermethylation of the nuclear respiratory factor 1 (NRF1) motif, an established upstream regulator of mitochondrial biogenesis. These preliminary observations are the first to uncover an etiology-independent shift in cardiac DNA methylation that corresponds with altered metabolic gene expression in HF. NEW & NOTEWORTHY The failing heart undergoes profound metabolic changes because of alterations in cardiac gene expression, reactivating glycolytic genes and suppressing oxidative metabolic genes. In the current study, we discover that alterations to cardiac DNA methylation encode this fetal-like metabolic gene reprogramming. We also identify novel epigenetic interference of nuclear respiratory factor 1 via hypermethylation of its downstream promoter targets, further supporting a novel contribution of DNA methylation in the metabolic remodeling of heart failure.

Background: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD. Methods: The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF Results: Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was −0.6 cm (interquartile range [IQR], −1.1 to −0.1 cm; nonresponders), −1.1 cm (IQR, −1.8 to −0.4 cm; partial responders), and −1.9 cm (IQR, −2.9 to −1.1 cm; responders). Similarly, the median change in LVEF was −2% (IQR, −6% to 1%), 9% (IQR, 6%–14%), and 27% (IQR, 23%–33%), respectively. Conclusions: Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations.

Introduction: Left ventricular assist device (LVAD) therapy aims to improve LV reverse remodeling, but still >50% of chronic heart failure (CHF) patients show ‘no’ recovery. The current clinical paradigm to assess post-LVAD myocardial recovery relies on ventricular rotational and deformational mechanics. Investigating the role of a pre-LVAD QRS as a potential indicator for post-LVAD LV recovery in CHF patients may help clinicians develop optimal care plans for LVAD patients. Hypothesis: Pre-LVAD short QRS has potential value to be useful as an independent predictor for early myocardial recovery following LVAD implantation. Methods: Chronic and dilated cardiomyopathy patients (n=315) undergoing LVAD implantation were retrospectively studied. Acute HF etiology and post-LVAD follow up (6 cm. From 315 LVAD patients, 39 fulfilled the criteria of myocardial recovery as ‘R’. Results: Based on univariate logistic regression, pre-LVAD QRS duration is found to be a predictor of myocardial recovery following LVAD implantation (OR:0.986, 95% CI:0.976-0.996, p=0.005) in LVAD patients. QRS duration is 14.5% longer in the ‘NR’ group as compared with the ‘R’ group (145±36 ms vs 124±37 ms). In multivariate logistic regression, after adjusting for previous thoracotomy, beta-blockers, and a previously evaluated composite score (UCARS) including age, HF duration, and LVEDD, pre-LVAD QRS remains a significant predictor of ‘R’ status (OR:0.983, 95% CL:0.973-0.994, p=0.003). The model shows an accuracy of 0.74 with a p-value of Conclusions: Pre-LVAD short QRS interval is associated with post-LVAD LV reverse remodeling in the ‘R’ group, and thus could be of use in a clinical setting for predicting post-LVAD early myocardial recovery.

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.

To describe the structural sequelae of carbon monoxide (CO) poisoning on the heart assessed using stress cardiac MRI (CMR). CO poisoning is common. While acute cardiac injury is frequent among survivors, the mid- and long-term effects of CO on the myocardium are unclear.CMR studies performed between the years 2005 and 2014 for a primary diagnosis of CO poisoning at a tertiary care center were reviewed by an experienced cardiologist. Variables of interest were compared between patients with normal and abnormal studies to identify factors associated with cardiac dysfunction.Eighty-eight patients underwent stress CMR, age 34 years (range 11-70); 49% were male, 74 had acute poisoning and 14 had chronic poisoning (CO exposure for longer than 24 hours). Time from CO poisoning to imaging was 24 months (1 day-120 months). Patients were stratified into four categories, which included those with acute poisoning imaged: ≤12 months; 12-60 months;60 months from the event; and those with chronic poisoning. Overall, 26 studies (30%) were abnormal. The most common findings were: left ventricular systolic dysfunction in 14 patients, right ventricular systolic dysfunction in nine, and LV dilatation in six. Abnormalities were mild in most cases and were equally prevalent in all four patient categories. Dyspnea at the time of follow-up was more frequent among those with abnormal studies.Mild alterations in ventricular structure and function are frequent in survivors of CO poisoning. Myocardial scarring is rare, suggesting that acute hypoxic injury may not fully explain these abnormalities.

Background: Significant improvements in myocardial structure and function have been reported in some patients with advanced heart failure (termed responders [R]) following left ventricular assist device (LVAD)–induced mechanical unloading. This therapeutic strategy may alter myocardial energy metabolism in a manner that reverses the deleterious metabolic adaptations of the failing heart. Specifically, our previous work demonstrated a post-LVAD dissociation of glycolysis and oxidative-phosphorylation characterized by induction of glycolysis without subsequent increase in pyruvate oxidation through the tricarboxylic acid cycle. The underlying mechanisms responsible for this dissociation are not well understood. We hypothesized that the accumulated glycolytic intermediates are channeled into cardioprotective and repair pathways, such as the pentose-phosphate pathway and 1-carbon metabolism, which may mediate myocardial recovery in R. Methods: We prospectively obtained paired left ventricular apical myocardial tissue from nonfailing donor hearts as well as R and nonresponders at LVAD implantation (pre-LVAD) and transplantation (post-LVAD). We conducted protein expression and metabolite profiling and evaluated mitochondrial structure using electron microscopy. Results: Western blot analysis shows significant increase in rate-limiting enzymes of pentose-phosphate pathway and 1-carbon metabolism in post-LVAD R (post-R) as compared with post-LVAD nonresponders (post-NR). The metabolite levels of these enzyme substrates, such as sedoheptulose-6-phosphate (pentose phosphate pathway) and serine and glycine (1-carbon metabolism) were also decreased in Post-R. Furthermore, post-R had significantly higher reduced nicotinamide adenine dinucleotide phosphate levels, reduced reactive oxygen species levels, improved mitochondrial density, and enhanced glycosylation of the extracellular matrix protein, α-dystroglycan, all consistent with enhanced pentose-phosphate pathway and 1-carbon metabolism that correlated with the observed myocardial recovery. Conclusions: The recovering heart appears to direct glycolytic metabolites into pentose-phosphate pathway and 1-carbon metabolism, which could contribute to cardioprotection by generating reduced nicotinamide adenine dinucleotide phosphate to enhance biosynthesis and by reducing oxidative stress. These findings provide further insights into mechanisms responsible for the beneficial effect of glycolysis induction during the recovery of failing human hearts after mechanical unloading.

Background: Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. Methods: In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II–III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2–4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545. Findings: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned to mavacamten (n=123 [49%]) or placebo (n=128 [51%]). 45 (37%) of 123 patients on mavacamten versus 22 (17%) of 128 on placebo met the primary endpoint (difference +19·4%, 95% CI 8·7 to 30·1; p=0·0005). Patients on mavacamten had greater reductions than those on placebo in post-exercise LVOT gradient (−36 mm Hg, 95% CI −43·2 to −28·1; p2 (+1·4 mL/kg per min, 0·6 to 2·1; p=0·0006), and improved symptom scores (KCCQ-CSS +9·1, 5·5 to 12·7; HCMSQ-SoB −1·8, −2·4 to −1·2; p

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.

Purpose Diabetes mellitus (DM) is prevalent among advanced heart failure (HF) patients, however its effect on the potential of left ventricular assist device (LVAD)-mediated cardiac recovery has not been described. Methods Consecutive advanced chronic HF patients (N=425) requiring durable continuous-flow LVAD were prospectively evaluated. After excluding patients with acute HF etiologies or post-LVAD follow up Results Baseline characteristics of the 2 groups are shown in the Table. Cardiac functional and structural improvement, as evidenced by relative LVEF and LVEDD changes, was more prominent in non-DM compared to DM patients, and in well- compared to not well-controlled DM patients (Figure). Overall, DM patients were less likely to experience cardiac recovery (8.4% vs 17.5%; p=0.032), while on LVAD support. This remained significant in a multivariate logistic regression after controlling for potential confounders. Conclusion The presence of DM, and notably not well-controlled DM, appears to negatively affect the potential for LVAD-induced myocardial recovery. Further research is needed to investigate the dynamic cardiac metabolism in HF with DM.

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.

Survival beyond 1 year after heart transplantation has remained without significant improvement for the last 2 decades. A more individualized approach to post-transplant care could result in a reduction of long-term mortality. Although recipient age has been associated with an increased incidence of certain post-transplant morbidities, its effect on cause-specific mortality has not been established.We analyzed overall and cause-specific mortality of heart transplant recipients registered in the International Society for Heart and Lung Transplantation Registry between 1995 and 2011. Patients were grouped by recipient age: 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥ 70 years. Multivariable regression models were used to examine the association between recipient age and leading causes of post-transplant mortality. We also compared immunosuppression (IS) use among the different recipient age groups.There were 52,995 recipients (78% male; median age [5th, 95th percentile]: 54 [27, 66] years). Survival through 10 years after transplant was lower in heart transplant recipients in the 2 more advanced age groups: 49% for 60 to 69 years and 36% for ≥ 70 years (p0.01 for pairwise comparisons with remaining groups). The risk of death caused by acute rejection (hazard ratio [HR], 4.11; p0.01), cardiac allograft vasculopathy (HR, 2.85; p0.01), and graft failure (HR, 2.29; p0.01) was highest in the youngest recipients (18-29 years) compared with the reference group (50-59 years). However, the risk of death caused by infection (HR, 2.10; p0.01) and malignancy (HR, 2.23; p0.01) was highest in older recipients (≥ 70 years). Similarly, the risk of death caused by renal failure was lower in younger recipients than in the reference group (HR, 0.53; p0.01 for 18-49 years vs 50-59 years). The use of induction IS was similar among the different recipient age groups, and differences in maintenance IS were not clinically important.Causes of death in this large cohort of heart transplant recipients varied significantly with recipient age at the time of transplant, with cause-specific mortality profiles suggesting a possible effect of inadequate IS in younger recipients and over-IS in older recipients. Thus, a more personalized approach, possibly including different IS strategies according to recipient age, might result in improved post-transplant survival.

Purpose There is limited information on regional variation in rates of cardiac recovery and left ventricular assist device (LVAD) explantation at a global level. We aimed to compare the rates of cardiac recovery and LVAD explantation across several world regions. Methods LVAD recipients registered in the International Registry for Mechanically Assisted Circulatory Support (IMACS) were analyzed. Cardiac recovery was defined as follow-up LVEF >40% and a pre-LVAD LVEF Results A total of 16,029 patients met our inclusion criteria and were included in the analysis. Of these, 9,381 patients had at least one follow-up echocardiogram and a minimum of 3 months of LVAD support. Cardiac recovery was achieved in 13.3% (n=1,249) of patients, with a rate of 55.3% (n=21) in BTR compared with 13.1% (n=1,228) in non-BTR patients. Rates of cardiac recovery varied significantly by region: 12.7% (n=1,079) in the Americas, 15.9% (n=94) in Asia-Pacific and 29.5% (n=76) in Europe (p Conclusion Global rates of both cardiac recovery and LVAD explantation are higher in patients implanted with a priori BTR strategy. Rates of cardiac recovery appear to be higher in Europe for reasons that warrant further investigation. The global rates of LVAD explantation are much lower compared to the corresponding cardiac recovery rates. This observation invites future investigations to identify the challenges in regards to LVAD weaning when recovery is identified, which could result in higher rates of LVAD explantation.

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.

Purpose Predicting cardiac structural and functional improvement in advanced heart failure (HF) patients before durable left ventricular assist device (LVAD) implantation remains challenging. Identifying clinical predictors could improve patient selection and impact clinical management. Methods Advanced chronic HF patients (N=652) supported with continuous-flow LVADs were evaluated. After excluding patients with acute HF etiologies or without adequate post-LVAD follow up ( Results In total, 10% of the LVAD patients were R. Univariate analysis showed that R were younger, had shorter HF symptoms duration, less need for diuretics and their LV were less dilated pre-LVAD. Further, R had higher acuity disease as evidenced by the higher vasoactive agents need, higher BNP and higher incidence of abnormal liver enzymes. The multivariate Cox regression (AUC=0.74; p Conclusion Younger patients with less LV dilation and shorter duration of HF are more likely to improve their cardiac function during LVAD support. Whether these characteristics also predict sustainability of improved cardiac function after LVAD weaning warrants further investigation.

Purpose The variability of left ventricular structural and functional improvement following continuous flow left ventricular assist device (LVAD) implantation is poorly understood. Methods The study consecutively enrolled 358 patients with confirmed chronic heart failure who required a durable LVAD across four study sites. Echocardiograms were performed preceding LVAD implantation and serially up to a year after. Patients were categorized by the degree of structural (left ventricular internal diastolic diameter, LVIDd) and functional (left ventricular ejection fraction, LVEF) change after LVAD. Results In the cohort, 34 patients (10%) experienced improvement of the LVEF ≥40% and LVIDd ≤6.0cm and were termed responders. The rest of the patients were distinguished in 3 groups based on the absolute change (Δ) in LVEF during follow up: Partial Responders had Δ-LVEF ≥10% (n=57, 16%), Borderline Responders Δ-LVEF 5-10% (n=55, 15%), Non-Responders Δ-LVEF Conclusion Reverse left ventricular remodeling associated with durable LVAD support is not an all or none phenomenon and manifests in a continuous spectrum. Defining four stages across this continuum can inform clinical management and facilitate advancing the field of myocardial plasticity by informing the design of future investigations.

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.

Progress in precision medicine is limited by insufficient knowledge of transcriptomic or proteomic features in involved tissues that define pathobiological differences between patients. Here, myectomy tissue from patients with obstructive hypertrophic cardiomyopathy and heart failure is analyzed using RNA-Seq, and the results are used to develop individualized protein-protein interaction networks. From this approach, hypertrophic cardiomyopathy is distinguished from dilated cardiomyopathy based on the protein-protein interaction network pattern. Within the hypertrophic cardiomyopathy cohort, the patient-specific networks are variable in complexity, and enriched for 30 endophenotypes. The cardiac Janus kinase 2-Signal Transducer and Activator of Transcription 3-collagen 4A2 (JAK2-STAT3-COL4A2) expression profile informed by the networks was able to discriminate two hypertrophic cardiomyopathy patients with extreme fibrosis phenotypes. Patient-specific network features also associate with other important hypertrophic cardiomyopathy clinical phenotypes. These proof-of-concept findings introduce personalized protein-protein interaction networks (reticulotypes) for characterizing patient-specific pathobiology, thereby offering a direct strategy for advancing precision medicine., Understanding patient-specific pathobiological pathways is a critical step for advancing precision medicine. Here the authors show that individualized protein-protein interaction networks provide key insight on patient-level pathobiology and clinically relevant pathophenotypic characteristics in a complex disease.

Background Occasionally new onset cardiomyopathy patients (pts) present late and with such advanced disease stage that they cannot tolerate heart failure (HF) drug therapy. We sought to investigate the cardiac recovery (CR) potential following a combination of left ventricular assist device (LVAD) and guideline-directed HF drug therapy in this medication-naive population. Methods Chronic advanced HF requiring durable continuous-flow LVAD were prospectively evaluated. Patients with acute HF (myocarditis etc.) or post LVAD follow up Results Univariate analysis showed that “med-naive” patients were younger, more likely to be on intravenous vasoactive agents, temporary mechanical support and with lower INTERMACS profile before LVAD implantation. Interestingly, no differences were seen in HF symptoms duration or other comorbidities. Baseline and follow up hemodynamics were similar in both groups, besides higher right atrial pressure pre-LVAD in the “meds-naive” group (16 vs 11 mmHg; p=0.04). Baseline echocardiographic (including LV dilation) and biochemical parameters revealed no differences between the groups, besides lower LVEF and higher BNP in the “meds-naive” group (14 vs 19%; p=0.03 and 2352 vs 1270; p=0.03, respectively). CR rates were significantly higher on “meds-naive” versus “meds-failed” group (50.0 vs 13.8%; p=0.005). Despite higher cardiac recovery rates in the “meds-naive” group the time course and magnitude of the favorable functional and structural response was similar among the CR responders of each of the 2 groups. Conclusion Young patients with new onset dilated cardiomyopathy sometimes present late, with advanced disease stage, unable to tolerate HF medications and requiring durable LVAD support. This patient population appears to have a potential for CR up to 50% and this could be factored in decisions surrounding their long-term therapeutic options.

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.

Background: The coronary vasculature encounters a reduction in pulsatility after implementing durable continuous-flow left ventricular assist device (CF-LVAD) circulatory support. Evidence exists that appropriate pulsatility is required to maintain endothelial cell homeostasis. We hypothesized that coronary artery endothelial function would be impaired after CF-LVAD intervention. Methods and Results: Coronary arteries from patients with end-stage heart failure caused by ischemic cardiomyopathy (ICM; n=16) or non-ICM (n=22) cardiomyopathy were isolated from the left ventricular apical core, which was removed for the CF-LVAD implantation. In 11 of these patients, paired coronary arteries were obtained from an adjacent region of myocardium after the CF-LVAD intervention (n=6 ICM, 5 non-ICM). Vascular function was assessed ex vivo using isometric tension procedures in these patients and in 7 nonfailing donor controls. Maximal endothelium-dependent vasorelaxation to BK (bradykinin; 10 − 6 –10 − 10 M) was blunted ( P −4 –10 −9 M) were similar among the groups. Contrary to our hypothesis, vasorelaxation responses to BK and sodium nitroprusside were similar before and 219±37 days after CF-LVAD support. Of these patients, an exploratory subgroup analysis revealed that BK-induced coronary artery vasorelaxation was greater ( P Conclusions: Coronary artery endothelial function is not impaired by durable CF-LVAD support and in ICM patients appears to be improved. Investigating coronary endothelial function using in vivo approaches in a larger patient population is warranted.

Current continuous-flow left ventricular assist devices (LVADs) decrease peripheral vascular pulsatility, which may contribute to side effects such as bleeding and thrombotic events. However, the actual impact of manipulating LVAD pump speed, revolutions per minute (rpm), on peripheral (brachial) pulsatility index (brachial PI), in patients with heart failure implanted with a HeartWare (HVAD) or HeartMateII (HMII) LVAD is unknown. Therefore, blood velocities (Doppler ultrasound) in the brachial artery were recorded and brachial PI calculated across rpm manipulations which spanned the acceptable clinical outpatient range: 360 rpm (HVAD, n = 10) and 1200 rpm (HMII, n = 10). Left ventricular assist device-derived PIs were also recorded: HVAD maximal blood flow (HVADV max), HVAD minimum blood flow (HVADV min), and HMII PI (HMIIPI). Brachial PI changed significantly with rpm manipulations, from 2.3 ± 0.6 to 4.1 ± 0.8 (HVAD) and from 1.8 ± 0.5 to 3.6 ± 1.0 (HMII). Multilevel linear modeling with random intercepts revealed a 180 rpm decrease of the HVAD resulted in a 0.9 ± 0.1 (37 ± 4%, d = 2.65) increase in brachial PI and a 600 rpm decrease in the HMII resulted in a 0.8 ± 0.1 (38 ± 3%, d = 4.66) increase. Furthermore, a reduction in rpm resulted in a 20.0 ± 0.3% power savings, and a reduction in device reported blood flow of 9 ± 1%. Brachial PI was linearly related to HVADV max, HVADV min, their difference (R = 0.42, R = 0.65, and R = 0.54, respectively), and HMIIPI (R = 0.86). Manipulating LVAD pump speed, within a clinically acceptable outpatient range, resulted in a significant change in brachial PI, which was reflected by pump indices, documenting the potential for LVAD pump speed manipulations to improve LVAD outcomes.

Purpose Despite several models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support, poor performance when externally validated has limited their widespread use. We sought to derive a predictive model for RVF after LVAD implantation, and ascertain its performance in an independent cohort. Methods End-stage heart failure (HF) patients requiring continuous-flow LVAD were prospectively enrolled at one US program (n=477, derivation cohort), with two other US medical centers forming the validation cohort (n=321). The primary outcome was RVF incidence, defined as the need for right ventricular assist device or inotropes for >14 days. Multivariable logistic regression in the derivation set yielded a RVF predictive model, which was subsequently applied to the validation cohort, and a risk score was ultimately developed. Results Derivation cohort included patients less likely to be African-Americans (7% vs 37%; p Conclusion We propose a novel scoring system to predict post-LVAD RVF, achieving high discriminative performance in distinct, heterogeneous LVAD cohorts.

Purpose Substantial total body weight (TBW) gain is frequently observed after heart transplant (HT), but little is known about the effect of the rate of weight change on outcomes. We assessed the pattern of post-HT change in TBW and its impact on outcomes. Methods Post-HT changes in TBW, fat mass (FM) and fat-free mass (FFM) were examined for 15,182 adult recipients in the ISHLT Registry transplanted between 1996 and 2016 who survived to 1 year and for whom serial body weight data were recorded. Patients were stratified into quartiles of 1-year TBW percent change. Endpoints included treated rejection (TR), cardiac allograft vasculopathy (CAV), and all-cause mortality. Results TBW gain was seen in a large number of patients after HT, such that the proportion of obese patients increased from 21% at HT to 30% at 1 year after HT (p Conclusion A large proportion of HT recipients are at risk of weight gain. Significant weight gain in the first year after transplant is associated with a risk of adverse outcomes, independent of absolute weight or BMI. Mitigation of the rate of weight gain, and especially the FM contribution to weight gain, could reduce post-transplant morbidity and mortality.