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BACKGROUND Despite some reports of cardiometabolic disorders associated with the risk of Alzheimer's disease (AD), limited studies have been conducted to examine the association between excessive sugar intake (a risk factor for cardiometabolic disorders) and AD risk. AIM The purpose of our study was to evaluate if excessive sugar intake has a significant long-term effect on the risk of AD. METHODS A population sample of 37,689 participants, who enrolled in the United States (US) Women's Health Initiative - Dietary Modification Trial (WHI-DM) in 1993-2005 and its extended observational follow-up study through 1 March 2019, were analyzed. Dietary sugar intake was measured using food frequency questionnaires. AD was classified by reports using a standard questionnaire. A dietary pattern that explained the maxima variations in sugar intake was constructed using reduced rank regression (RRR) technique. Associations of RRR dietary pattern scores and sugar intake (g/day) by quartiles (Q1 through Q4) with AD risk were examined using Cox proportional hazards regression analysis with adjusting for key covariates. RESULTS During a mean follow-up of 18.7 years, 4586 participants reported having incident AD. The total incidence rate (95% confidence interval [CI]) of AD was 6.5 (6.3-6.7) per 1000 person-years (PYs). The incidence rates (95% CI) of AD by total sugar intake were 6.2 (5.8-6.6), 6.4 (6.0-6.8), 6.6 (6.3-7.0), and 6.9 (6.5-7.3) per 1000 PYs among those in quartiles (Q) 1 to Q4 (toward higher sugar consumption) of total sugar intake, respectively (test for trend of AD incident rates, p

A consensus conference on frailty in solid organ transplantation took place on February 11, 2018, to discuss the latest developments in frailty, adopt a standardized approach to assessment, and generate ideas for future research. The findings and consensus of the Frailty Heart Workgroup (American Society of Transplantation's Thoracic and Critical Care Community of Practice) are presented here. Frailty is defined as a clinically recognizable state of increased vulnerability resulting from aging-associated decline in reserve and function across multiple physiologic systems such that the ability to cope with every day or acute stressors is compromised. Frailty is increasingly recognized as a distinct biologic entity that can adversely affect outcomes before and after heart transplantation. A greater proportion of patients referred for heart transplantation are older and have more complex comorbidities. However, outcomes data in the pretransplant setting, particularly for younger patients, are limited. Therefore, there is a need to develop objective frailty assessment tools for risk stratification in patients with advanced heart disease. These tools will help to determine appropriate recipient selection for advanced heart disease therapies including heart transplantation and mechanical circulatory support, improve overall outcomes, and help distinguish frailty phenotypes amenable to intervention.

BACKGROUND In spite of an increase in the incidence and prevalence of diabetes mellitus (DM) and Alzheimer’s disease (AD) in the aging population worldwide, limited attention has been paid to their potential association. AIM To investigate the association of DM and cardiometabolic syndrome (CMS, a precursor to DM) with risk of incident AD among postmenopausal women. METHODS Postmenopausal women aged 50-79 (n = 63117) who participated in the U.S. Women’s Health Initiative Observational Study (WHIOS), recruited in 1993-1998, without baseline AD and followed up through March 1, 2019, were analyzed. AD was classified by participant-reported history of doctor-diagnosis of incident AD in the WHIOS. DM was defined by participant-report or treated because of diabetes or serum glucose concentrations ≥ 126 mg/dL. CMS was defined as having ≥ 3 of five CMS components: large waist circumference, high blood pressure, elevated triglycerides, elevated glucose, and low high-density lipoprotein cholesterol. The associations of DM and CMS with AD were analyzed using Cox’s proportional hazards regression analysis. RESULTS During a median follow-up of 20 years (range: 3.36 to 23.36 years), of 63117 participants, 8340 developed incident AD. Women with DM had significantly higher incidence of AD [8.5, 95% confidence interval (CI): 8.0-9.0 per 1000 person-years (PY)] than those without DM (7.1, 95%CI: 6.9-7.2 per 1000 PY). Multivariate Cox’s regression analysis indicated that women with DM or CMS had a significantly higher risk of AD than those without DM or CMS. The corresponding hazard ratios [HR (95%CI)] were 1.22 (1.13-1.31, P < 0.001) in subjects with DM, and 1.18 (1.09-1.27, P < 0.001) in subjects with CMS. The HRs diminished with age and became non-significant in the oldest age group. CONCLUSION During a median follow-up of 20 years, DM and CMS were significantly associated with the risk of AD among postmenopausal women. More specifically, women aged 50-69 with DM or CMS vs those without these conditions had significantly higher relative risks of AD than the relative risks of AD in those aged 70-79 with DM or CMS vs those without DM or CMS.

Aims Although heart failure with preserved ejection fraction (HFpEF) is a rapidly emerging global health problem, an adequate tool to screen it reliably and economically does not exist. We developed an interpretable deep learning model (DLM) using electrocardiography (ECG) and validated its performance. Methods and results This retrospective cohort study included two hospitals. 34 103 patients who underwent echocardiography and ECG within 1 week and indicated normal left ventricular systolic function were included in this study. A DLM based on an ensemble neural network was developed using 32 671 ECGs of 20 169 patients. The internal validation included 1979 ECGs of 1979 patients. Furthermore, we conducted an external validation with 11 955 ECGs of 11 955 patients from another hospital. The endpoint was to detect HFpEF. During the internal and external validation, the area under the receiver operating characteristic curves of a DLM using 12-lead ECG for detecting HFpEF were 0.866 (95% confidence interval 0.850–0.883) and 0.869 (0.860–0.877), respectively. In the 1412 individuals without HFpEF at initial echocardiography, patients whose DLM was defined as having a higher risk had a significantly higher chance of developing HFpEF than those in the low-risk group (33.6% vs. 8.4%, P Conclusion The DLM demonstrated high performance for HFpEF detection using not only a 12-lead ECG but also 6- single-lead ECG. These results suggest that HFpEF can be screened using conventional ECG devices and diverse life-type ECG machines employing the DLM, thereby preventing disease progression.

Purpose: To examine the burden of uncontrolled hyperglycemia in patients with diabetes mellitus (DM) and their characteristics in a large urban city. Methods: A randomized sample of 4993 patients with DM ≥18 years old who received routine health care in a large university teaching hospital in the city of Philadelphia was analyzed. Uncontrolled hyperglycemia was classified as blood hemoglobin A1c >8%. The associations of uncontrolled hyperglycemia with sociodemographic and cardiovascular factors were analyzed using univariate and multivariate analysis methods. Results: The results show that patients 18–54 years had the highest prevalence of uncontrolled hyperglycemia (36.0%), followed by those at age 55–64 (30.9%), 65–74 (22.9%), and ≥75 (20.6%) years (p

Among the estimated 6.2 million Americans living with heart failure (HF), ≈5%/y may progress to advanced, or stage D, disease. Advanced HF has a high morbidity and mortality, such that early recognition of this condition is important to optimize care. Delayed referral or lack of referral in patients who are likely to derive benefit from an advanced HF evaluation can have important adverse consequences for patients and their families. A 2-step process can be used by practitioners when considering referral of a patient with advanced HF for consideration of advanced therapies, focused on recognizing the clinical clues associated with stage D HF and assessing potential benefits of referral to an advanced HF center. Although patients are often referred to an advanced HF center to undergo evaluation for advanced therapies such as heart transplantation or implantation of a left ventricular assist device, there are other reasons to refer, including access to the infrastructure and multidisciplinary team of the advanced HF center that offers a broad range of expertise. The intent of this statement is to provide a framework for practitioners and health systems to help identify and refer patients with HF who are most likely to derive benefit from referral to an advanced HF center.

Background: Long-term oral anticoagulants (OAC) increases bleeding risk after the percutaneous coronary intervention (PCI) with dual antiplatelet therapy (DAPT) with Aspirin and P2Y12 inhibitors. We hypothesize that dual anti-thrombotic therapy (DATT) reduces bleeding without increased cardiovascular events. Objectives: DATT does not increase adverse cardiovascular events compared to triple anti-thrombotic therapy (TATT). Method: We searched MEDLINE, PUBMED, Google Scholar, Cochrane and EMBASE from inception to 6 April 2019 for randomized control trials (RCTs) comparing DATT to TATT after PCI. Results: We identified 641 citations (411 after excluding duplicates). Four RCTs with 5,317 patients (3,039 on DATT vs 2,278 on TATT) were included. DATT arm showed significantly reduced [total bleeding, 731 vs. 784, odds ratio [OR] = 0.51, Confidence Interval [CI] = 0.39–0.67, p < 0.00001, I2 = 71% (I2 = 0% without WOEST study)], [TIIMI major bleeding 60 vs. 80, OR = 0.56, CI = 0.4–0.79, p = 0.0009, I2 = 0%], and [TIIMI minor bleeding, 70 vs 126, OR = 0.43, CI = 0.32–0.59, p < 0.00001, I2 = 0%]. There was no difference in subsequent strokes, myocardial infarction, stent thrombosis, and mortality. A trend towards decreased non-cardiac deaths with DATT was observed, 14 vs 26, OR = 0.55, CI = 0.27–1.10, p = 0.09, I2 = 6%. Conclusions: DATT is associated with significantly reduced bleeding and a trend towards reduced non-cardiac death with no difference in adverse cardiovascular outcomes.

Antiproliferative agents include Mycophenolic acid and Azathioprine (which is less commonly used unless in certain conditions). They were initially identified for use in autoimmune and cancer research due to their role in disruption of cellular replication. They have now become the cornerstone of antirejection maintenance therapy in solid organ transplant. In this chapter we will describe the major times that lead to discovery, mechanisms of action, side effects, use during pregnancy and the major clinical trials.

Transthyretin amyloid cardiomyopathy (ATTR-CM) results in a restrictive cardiomyopathy caused by extracellular deposition of transthyretin, normally involved in the transportation of the hormone thyroxine and retinol-binding protein, in the myocardium. Enthusiasm about ATTR-CM has grown as a result of 3 simultaneous areas of advancement: Imaging techniques allow accurate noninvasive diagnosis of ATTR-CM without the need for confirmatory endomyocardial biopsies; observational studies indicate that the diagnosis of ATTR-CM may be underrecognized in a significant proportion of patients with heart failure; and on the basis of elucidation of the mechanisms of amyloid formation, therapies are now approved for treatment of ATTR-CM. Because therapy for ATTR-CM may be most effective when administered before significant cardiac dysfunction, early identification of affected individuals with readily available noninvasive tests is essential. This scientific statement is intended to guide clinical practice and to facilitate management conformity by covering current diagnostic and treatment strategies, as well as unmet needs and areas of active investigation in ATTR-CM.

Backgrounds The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread worldwide. Cardiac injury after SARS-CoV-2 infection is a major concern. The present study investigated impact of the biomarkers indicating cardiac injury in coronavirus disease 2019 (COVID-19) on patients' outcomes. Methods This study enrolled patients who were confirmed to have COVID-19 and admitted at a tertiary university referral hospital between February 19, 2020 and March 15, 2020. Cardiac injury was defined as an abnormality in one of the following result markers: 1) myocardial damage marker (creatine kinase-MB or troponin-I), 2) heart failure marker (N-terminal-pro B-type natriuretic peptide), and 3) electrical abnormality marker (electrocardiography). The relationship between each cardiac injury marker and mortality was evaluated. Survival analysis of mortality according to the scoring by numbers of cardiac injury markers was also performed. Results A total of 38 patients with COVID-19 were enrolled. Twenty-two patients (57.9%) had at least one of cardiac injury markers. The patients with cardiac injuries were older (69.6 ± 14.9 vs. 58.6 ± 13.9 years old, P = 0.026), and were more male (59.1% vs. 18.8%, P = 0.013). They showed lower initial oxygen saturation (92.8 vs. 97.1%, P = 0.002) and a trend toward higher mortality (27.3 vs. 6.3%, P = 0.099). The increased number of cardiac injury markers was significantly related to a higher incidence of in-hospital mortality which was also evidenced by Kaplan-Meier survival analysis (P = 0.008). Conclusion The increased number of cardiac injury markers is related to in-hospital mortality in patients with COVID-19., Graphical Abstract

Background Recent randomized control trials (RCTs) have suggested benefit with transcatheter patent foramen ovale (PFO) closure plus antiplatelet therapy over medical treatment alone for secondary stroke prevention. Material and Methods Data sources: we searched PubMed and Ovid MEDLINE from the inception until November 10, 2017 for RCTs comparing TPFO closure to medical therapy in patients with a PFO and a history of cryptogenic stroke. Results Five RCTs with 3,627 patients (TPFO closure = 1,829 versus medical therapy =1,798) were included. There was a decreased number of post-TPFO closure strokes compared to the medical therapy arm; 53 versus 80 strokes (odds ratio [OR] = 0.61, CI: 0.39-0.94, P = 0.03, I2 = 17%). Transient ischemic attacks occurred in 43 patients after TPFO closure versus 60 patients in the medical therapy group (OR = 0.80, CI: 0.53-1.19, P = 0.26, I2 = 0%). There was a higher incidence of atrial fibrillation in the TPFO closure group, which occurred in 75 patients, compared to 12 patients in the medical therapy group (OR = 5.23, CI: 2.17-12.59, P = 0.0002, I2 = 43%). There was a trend toward a decreased number of neuropsychiatric events in the TPFO closure closure group compared to the medical therapy group; 42 versus 67 neuropsychiatric events (OR = 0.71, CI: 0.48-1.06, P = 0.09, I2 = 0%). Conclusions TPFO closure plus antiplatelet therapy is superior to medical therapy in patients with a PFO and cryptogenic stroke. PFO closure is associated with new-onset atrial fibrillation and a trend toward reduced neuropsychiatric events.

Acute kidney injury (AKI) is commonly associated with aortic valve replacement. Surgical aortic valve replacement (SAVR) is a known risk factor for AKI but little is known about the short- and long-term effects of transcatheter aortic valve implantation (TAVI). The purpose of our analysis is to identify the short- and long-term effect of TAVI on renal outcomes. We searched Medline and PUBMED from January 1, 2000 to November 6, 2017 for randomized control trials (RCTs) comparing TAVI to SAVR in patients with severe aortic stenosis. Three hundred sixty-nine trials were identified, 6 RCTs were included in our analysis. RevMan version 5.3 was used for statistical analysis. Heterogeneity is calculated using I2 statistics. Primary outcomes were AKI within 30 days and 1 year of TAVI, and requirement for renal replacement therapy. We included 5,536 patients (2,796 in TAVI and 2,740 in SAVR arm) from 6 RCTs. Baseline characteristics were similar. There was reduced incidence of AKI at 30 days of TAVI compared with SAVR, 57 versus 133 (odds ratio [OR] 0.40, confidence interval [CI] 0.28 to 0.56, p

Implantable cardioverter-defibrillator (ICD) has shown to reduce sudden cardiac death and overall mortality in patients with dilated cardiomyopathy. The recently published DANISH trial has shown conflicting outcomes on the long-term survival in patients with prophylactic implantation of ICD in Non-Ischemic Cardiomyopathy (NICM). Two independent reviewers searched MEDLINE, PUBMED, Ovid, CINAHL, clinicaltrials.gov , and Cochrane Registry for randomized control trials (RCT’s) comparing ICD to medical treatment (MT). Six RCT’s enrolling 3389 patients (ICD = 1554 and MT = 1835) were included for final analysis. The primary outcomes were mortality comparing ICD to MT, 231 vs 337 (OR = 0.74, CI = 0.62–0.90, p = 0.002, and I2 = 0%) favoring ICD. On comparing to amiodarone only, there were 47 deaths in the ICD arm vs 71 deaths in amiodarone arm, (OR = 0.66, CI = 0.44–0.98, p = 0.04, I2 0%), to placebo and usual care only (excluding amiodarone); there were 225 deaths in ICD patients compared to 266 in the placebo and usual care arm, (OR = 0.73, CI = 0.59–0.92, p = 0.007, I2 = 15%). The results of our analysis from these six RCTs clearly support the ongoing benefit of prophylactic ICD implantation and support current recommendations for ICD implantation in NICM patients. More RCT’s at a larger scale are needed to further elucidate benefits of both ICD and CRT-D in this post PARADIGM era where MT is at a pinnacle in reducing morbidity and mortality in heart failure patients.

Malignancy is a concern in cardiac transplant recipients, but the temporal trends of de novo malignancy development are unknown.The goal of this study was to describe the temporal trends of the incidence, types, and predictors of de novo malignancy in cardiac transplant recipients.The authors analyzed the temporal trends of post-transplant incidence, types, and predictors of malignancy using 17,587 primary adult heart-only transplant recipients from the International Society for Heart and Lung Transplantation registry. The main study outcomes included the incidence of, types of, and time to de novo malignancy.The risk of any de novo solid malignancy between years 1 and 5 after transplantation was 10.7%. The cumulative incidence by malignancy type was: skin cancer (7.0%), non-skin solid cancer (4.0%), and lymphoproliferative disorders (0.9%). There was no temporal difference in the time to development according to malignancy type. However, the cumulative incidence of de novo solid malignancy increased from 2000 to 2005 vs. 2006 to 2011 (10.0% vs. 12.4%; p 0.0001). Survival in patients after de novo malignancy was markedly lower than in patients without malignancy (p 0.0001). Older recipients and patients who underwent transplantation in the recent era had a higher risk of de novo malignancy.More than 10% of adult heart transplant recipients developed de novo malignancy between years 1 and 5 after transplantation, and this outcome was associated with increased mortality. The incidence of post-transplant de novo solid malignancy increased temporally, with the largest increase in skin cancer. Individualized immunosuppression strategies and enhanced cancer screening should be studied to determine whether they can reduce the adverse outcomes of post-transplantation malignancy.

Cardiac transplantation remains the only definitive treatment for end-stage heart failure. Transplantation rates are limited by a shortage of donor hearts. This shortage is magnified because many hearts are discarded because of strict selection criteria and concern for regulatory reprimand for less-than-optimal posttransplant outcomes. There is no standardized approach to donor selection despite proposals to liberalize acceptance criteria. A donor heart selection conference was organized to facilitate discussion and generate ideas for future research. The event was attended by 66 participants from 41 centers with considerable experience in cardiac donor selection. There were state-of-the-art presentations on donor selection, with subsequent breakout sessions on standardizing the process and increasing utilization of donor hearts. Participants debated misconceptions and established agreement on donor and recipient risk factors for donor selection and identified the components necessary for a future donor risk score. Ideas for future initiatives include modification of regulatory practices to consider extended criteria donors when evaluating outcomes and prospective studies aimed at identifying the factors leading to nonacceptance of available donor hearts. With agreement on the most important donor and recipient risk factors, it is anticipated that a consistent approach to donor selection will improve rates of heart transplantation.

We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P1R) with an area under the curve of 0.87 (P&nbsp

Graft allocation rules for heart transplantation are necessary because of the shortage of heart donors, resulting in high waitlist mortality. The Agence de la biomedecine is the agency in charge of the organ allocation system in France. Assessment of the 2004 urgency-based allocation system identified challenging limitations. A new system based on a score ranking all candidates was implemented in January 2018. In the revised system, medical urgency is defined according to candidate characteristics rather than the treatment modalities, and an interplay between urgency, donor-recipient matching, and geographic sharing was introduced. In this article, we describe in detail the new allocation system and compare these allocation rules to Eurotransplant and US allocation policies.

Congestive heart failure is a major cause of morbidity and mortality as well as a major health care cost in the developed world. Despite the introduction of highly effective heart failure medical therapies and simple devices such as cardiac resynchronization therapy that reduce mortality, improve cardiac function and quality of life, there remains a large number of patients who do not respond to these therapies or whose heart failure progresses despite optimal therapy. For these patients, cardiac transplantation is an option but is limited by donor availability as well as co-morbidities which may limit survival post-transplant. For these patients, left ventricular assist devices (LVADs) offer an alternative that can improve survival as well as exercise tolerance and quality of life. These devices have continued to improve as technology has improved with substantially improved durability of the devices and fewer post-implant complications. Pump thrombosis, stroke, gastrointestinal bleeding and arrhythmias post-implant have become less common with the newest devices, making destination therapy where ventricular assist device are implanted permanently in patients with advanced heart failure, a reality and an appropriate option for many patients. This may offer an opportunity for long term survival in many patients. As the first of the totally implantable devices are introduced and go to clinical trials, LVADs may be introduced that may truly be alternatives to cardiac transplantation in selected patients. Post-implant right ventricular failure remains a significant complication and better ways to identify patients at risk as well as to manage this complication must be developed.

The success of organ transplantation depends on the prevention of the allograft rejection with immunosuppression. The three types of rejections are hyperacute, acute, and chronic and are categorized by when the rejection occurs, and the mechanisms of organ injury. The type of tissue, specificity and memory of the lymphocytes, and the type of organ being transplanted are factors that dictate the risk of the type of rejection that may occur.

AIM To examine the epidemic of diabetes mellitus (DM) and its impact on mortality from all-cause and cardiovascular disease (CVD), and to test the effect of antidiabetic therapy on the mortality in United States adults. METHODS The analysis included a randomized population sample of 272149 subjects ages ≥ 18 years who participated in the National Health Interview Surveys (NHIS) in 2000-2009. Chronic conditions (hypertension, DM and CVD) were classified by participants’ self-reports of physician diagnosis. NHIS-Mortality Linked Files, and NHIS-Medical Expenditure Panel Survey Linkage Files on prescribed medicines for patients with DM were used to test the research questions. χ2, Poisson and Cox’s regression models were applied in data analysis. RESULTS Of all participants, 22305 (8.2%) had DM. The prevalence of DM significantly increased from 2000 to 2009 in all age groups (P < 0.001). Within an average 7.39 (SD = 3) years of follow-up, male DM patients had 1.56 times higher risk of death from all-cause (HR = 1.56, 95%CI: 1.49-1.64), 1.72 times higher from heart disease [1.72 (1.53-1.93)], 1.48 times higher from cerebrovascular disease [1.48 (1.18-1.85)], and 1.67 times higher from CVD [1.67 (1.51-1.86)] than subjects without DM, respectively. Similar results were observed in females. In males, 10% of DM patients did not use any antidiabetic medications, 38.1% used antidiabetic monotherapy, and 51.9% used ≥ 2 antidiabetic medications. These corresponding values were 10.3%, 40.4% and 49.4% in females. A significant protective effect of metformin monotherapy or combination therapy (except for insulin) on all-cause mortality and a protective but non-significant effect on CVD mortality were observed. CONCLUSION This is the first study using data from multiple linkage files to confirm a significant increased prevalence of DM in the last decade in the United States. Patients with DM have significantly higher risk of death from all-cause and CVD than those without DM. Antidiabetic mediations, specifically for metformin use, show a protective effect against all-cause and CVD mortalities.

Purpose Renal replacement therapy (RRT) post-LVAD implantation is often needed due to post-operative complications from AKI and pre-implant cardio-renal syndrome. RRT can assist with post-operative renal function recovery, but long-term use is associated with complications and poor outcomes. Identifying risk factors that increase the likelihood of RRT initiation and withdrawal post-LVAD can help multi-disciplinary teams risk-stratify patients to improve outcomes. Methods A retrospective chart review from 2018 to 2019 was conducted on 26 LVAD recipients (53.9% INTERMACS Class I) in our program. Patients on RRT prior to LVAD implantation were excluded. Clinical, laboratory, and outcomes data were compared between RRT (n=11) and no RRT (n=15) patients and between RRT recipients who continued (n=4) and withdrew (n=7). RRT withdrawal was defined as stopping RRT before hospital discharge. Bivariate analyses performed with T-test, Wilcoxon Rank-Sum Test, Chi-square, and Fisher's Exact test. Logistic regression with backward elimination used to predict RRT initiation and withdrawal. Results Patients on RRT were less healthy compared to patients not on RRT. More patients on RRT had hypertension (p=0.01) and history of myocardial infarction (p=0.05). Patients requiring RRT had longer mean hospitalizations (50.5 vs 30.3 days, p =0.01). Pre-operative renal function characterized by BUN, Cr, and eGFR were worse among RRT recipients (p=0.02, 0.04, and 0.04), respectively. Adjusting for age and sex, our reduced model identified a 12% increase in RRT initiation for each 1mg/dL increase in BUN prior to LVAD implantation (p=0.03). Patients withdrawing or continuing RRT post-LVAD were similar in terms of co-morbidities and hemodynamics. INTERMACS Class I was not associated with RRT initiation or withdrawal. Patients withdrawing from RRT had better renal function than those who continued. A serum biomarker, LDH (U/L), was elevated after (p=0.01) LVAD implantation among patients who withdrew from RRT. Conclusion Pre-operative renal function was significantly worse among LVAD recipients requiring post-implantation RRT. LVAD recipients may benefit from optimization of renal function and identification of serum biomarkers prior and after surgery, which may reduce the number of patients requiring RRT after LVAD implantation.

Background Continuous flow left ventricular assist devices (cfLVADs) have improved outcomes for advanced Heart Failure (HF) patients. Recurrent HF continues to be a complication and clinical examination is limited by the nature of the LVAD therapy requiring better diagnostics to improve patient outcomes. Methods We describe a multisensory diagnostic in two LVAD patients. Results Two patients with end-stage HF supported with a HeartMate II and HeartMate III containing a multisensor diagnostic for HF (HeartLogic) presented to clinic with exercise intolerance. In both, exam revealed no elevation of venous pressure, lungs were clear and no heart sounds were appreciated above the normal LVAD hum. On right heart catheterization of patient A, RA pressure was 14 mmHg, PCWP 18 mmHg and CI 1.9 L/min/m2. LVAD speed was increased from 10,000 to 10,400 rpm. Similarly, elevated filling pressures were seen with patient B, who had LVAD speed increased as well. In both cases, S3 magnitude decreased following LVAD speed increase. Both patients later had outpatient alerts detected and diuretics were doubled until alert resolution. In each instance, the clinical events were associated with a HeartLogic alert, and remarkably, the S3 changed in manner consistent with the interventions that occurred although clinicians could not appreciate an S3. Conclusion These cases demonstrate that a multisensory HF diagnostic changes and alerts during clinically meaningful events that is useful in the management of LVAD patients.

Purpose Gene expression profile (GEP) monitoring by AlloMap® is ISHLT-guideline recommended for graft surveillance after heart transplant (HT). The Outcomes in AlloMap Registry (OAR) is an observational, prospective study of HT patients monitored by AlloMap. The effect of malignancy on AlloMap scores is not well characterized. The large cohort of OAR patients with clinical data associated with AlloMap scores permits this characterization. Methods Patients enrolled in the OAR study and >6 months post-HT were assessed for malignancy status and stratified by HT recipients with malignancy and those without. The malignancy groups were further stratified by non-skin cancers and skin cancers, where mean AlloMap scores were compared between groups. Results 135 patients in the OAR registry (1.4%) with de-novo malignancy (including skin cancer) and 9395 patients with no de-novo malignancy >6 months post-HT and associated AlloMap scores were identified. Mean AlloMap score in patients with malignancy was significantly higher than in patients without malignancy (30.9 vs 30.1; p=0.0354) (Table 1). For HT patients with skin cancer vs no malignancy, there was not a statistically significant difference between GEP scores (30.7 vs 30.1; p=0.1390). Conclusion AlloMap scores were higher in HT recipients with any malignancy compared to HT patients without malignancy; however, scores were not statistically significant when looking only at skin-cancer versus no malignancy. Although statistically significant, the absolute difference was only small and therefore unlikely to have clinical impact. The GEP score comprises changes in gene expression in peripheral blood mononuclear cells (PBMCs). Recently, malignancy has been shown to cause changes in gene expression in PBMCs, which may explain this observed difference. Further studies are warranted to replicate these findings and to determine whether cancer development causes an elevated AlloMap score.

Background The International Society for Heart & Lung Transplantation (ISHLT) guidelines for Mechanical Circulatory Support (MCS) includes assessment of four elements of psychosocial functioning prior to Left Ventricular Assist Device (LVAD) implantation. Information about the practices and impact of assessments of psychosocial functioning are limited. Objective To describe the psychosocial function assessment practices used within US LVAD programs and the influence of psychosocial assessment results on clinical decisions for LVAD patient selection. Methods In 2017, a cross-sectional survey of LVAD programs listed in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) (N = 164) was conducted to understand practices used for and the influence of psychosocial assessments for post-operative care planning decisions. Results Respondents included representatives of 69 LVAD programs from throughout the U.S. that implanted 64.8% of all U.S LVADs in 2016. More than 39 psychosocial screening instruments were used. Assessment of family, social and emotional support occurred most frequently (84.1% (n = 58) of programs assessed 100% of patients), but assessment was least likely to be conducted with standardized instruments (36.2%). Cognitive dysfunction was the least likely characteristic to be assessed (26.1% (n = 18) of programs assessed 100% of patients), but was most often conducted with standardized instruments (53.8% of programs). Twenty seven percent of programs used non-standardized instruments or patient observation. The influence of assessments on clinical decisions to implant an LVAD was most influential in the bridge to transplant pathway with 60% (n = 39) of respondents rating it very influential and least influential for patients in the destination therapy pathway with 39.4% (n = 26) of respondents. Conclusions Current psychosocial assessment practices in LVAD programs vary widely and often yield non-standardized, non-comparable data that may lead to variations in care and limit generation of an evidence base for decision making regarding psychosocial eligibility for LVAD implantation.

Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation and systolic function and is the most common among all cardiomyopathies. Familial DCM makes up a significant portion of cases, and approximately 40 genes are identified as involved in the pathogenesis of heart failure, each affecting a specific part of cellular mechanisms. The purpose of this review is to summarize recent findings and the current understanding of the most common gene mutations identified associated with DCM. Next-generation sequencing is a comprehensive gene analysis technique used to discover more mutation variants and also to learn about the impact of mutations in relationship to clinical presentations. A variety of techniques are utilized to study different gene mutations, such as genotype-phenotype association analysis or whole-exome sequencing, to understand the natural history of diseases. For certain genetic abnormalities, information is helpful in developing potential therapeutic treatment targeting mutations. More treatment options are hopeful with the understanding of specific genetic mutations and their pathogenic mechanism. It also suggests the importance of genetic assessment and counseling for family members of an affected patient, in order to provide potential early diagnosis and better clinical management of DCM.

Objective: Apolipoprotein L1 (APOL1), the major protein component of HDL, is identified having an association with renal disease in African Americans (AA). We assessed the hypothesis that the genetic variations in APOL1 (G1 and G2 alleles) are associated with risk of heart failure (HF), and this effect is modified by age. Methods: Subjects aged 21-75, with an estimated GFR (eGFR) of 20 to 70 ml/min/1.73 m 2 at baseline recruitments (April 2003-Sept 2008), who were free of HF participating in the Chronic Renal Insufficiency Cohort (CRIC) Study and followed-up through March 2013 are analyzed (White: 1335, AA:1323). The associations of APOL1 risk genotype (assessed by either 1 of the G1 and G2, or 2 of their combinations, i.e., G1/G1, G1/G2 or G2/G2) with incident HF and mortality are examined using Cox’s regression models. Results: Within a mean 7-year (SD: 2.1) follow-up, AA had a significantly higher incidence of HF than White (2.62 vs. 1.67 per 100 person-year (PY), p=0.006) in those aged Conclusion: African Americans with APOL1 risk alleles have significantly higher risk of HF and mortality than White. An additive genetic effect of the number of APOL1 risk alleles is shown among AA aged ≥65, but not in the younger adults. The modifying effect of age suggests that a possible 'different genetic-risk window' by ages warrants consideration in HF control and prevention.

Background and objectivesStudies that examined geographic variation in heart failure (HF) and its association with risk factors at county and state levels were limited. This study aimed to test a hypothesis that HF mortality is disproportionately distributed across the United States, and this variation is significantly associated with the county- and state-level prevalence of high blood pressure (HBP), diabetes, obesity and physical inactivity.MethodsData from 1,723 counties in 51 states (including District of Columbia as a state) on the age-adjusted prevalence of obesity, physical inactivity, HBP and diabetes in 2010, and age-adjusted HF mortality in 2013–2015 are examined. Geographic variations in risk factors and HF mortality are analyzed using spatial autocorrelation analysis and mapped using Geographic Information System techniques. The associations between county-level HF mortality and risk factors (level 1) are examined using multilevel hierarchical regression models, taking into consideration of their variations accounted for by states (level 2).ResultsThere are significant variations in HF mortality, ranging from the lowest 11.7 (the state of Vermont) to highest 85.0 (Mississippi) per 100,000 population among the 51 states. Age-adjusted prevalence of obesity, physical inactivity, HBP, and diabetes are positively and significantly associated with HF mortality. Multilevel analysis indicates that county-level HF mortality rates remain significantly associated with diabetes (β = 2.7, 95% CI: 1.7–3.7, p

Significance of ultrafiltration in acute decompensated heart failure remains unclear. We performed meta-analysis to determine its role in reducing readmissions after acute decompensated heart failure. MEDLINE was searched using PUBMED from inception to March 22, 2017 for prospective randomized control trials comparing ultrafiltration to diuretics in acute decompensated heart failure. Five hundred ninety studies were found; nine studies with 820 patients were included. Studies with renal replacement therapy bar ultrafiltration, chronic decompensated heart failure, and non-English language were excluded. RevMan Version 5.3 was used for analysis. The primary outcomes analyzed were cumulative and 90 days readmissions secondary to heart failure and all-cause readmissions. Baseline characteristics were similar. One hundred eighty-eight patients were readmitted with heart failure, 77 vs 111 favoring ultrafiltration; risk ratio (RR) = 0.71 (95% confidence interval (CI), 0.49–1.02, p = 0.07, I 2 = 47%). Ninety days readmissions were 43 vs 67 favoring ultrafiltration; RR = 0.65 (95%CI, 0.47–0.90, p = 0.01, I 2 = 0%). Ultrafiltration showed significantly higher fluid removal and weight loss. Hypotension was common in ultrafiltration (24 vs 13, OR = 2.06, 95%CI = 0.98–4.32, p = 0.06, I 2 = 0%). Ultrafiltration showed reduced 90 days heart failure readmissions and trend towards reduced cumulative hospital readmissions. Renal and cardiovascular outcomes and hospital stay were similar.

This review aims to summarize the growing body of literature of HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) with a focus on recent pharmacologics. HFrEF continues to be more widely investigated than HFpEF. Ivabradine and combinatorial treatment with sacubitril and valsartan are promising newly approved therapies. Other experimental therapies have emerged, which include Serelaxin, Empagliflozin, Neuregulin, and Omecamtive mecarbil, among others. These drugs need to continue to be investigated for safety and efficacy. We predict ivabradine and combinatorial treatment with sacubitril-valsartan to develop as a widespread therapy. New therapies should be aimed at treating HFpEF or target the cardiomyocyte itself.

Objective: We assessed the hypothesis that metformin use significantly decreases risk of all-cause and heart disease (HD) mortality in patients with diabetes mellitus (DM). Methods: Subjects with DM aged ≥30 (n=3612) participating in 1999 -2010 National Health and Nutrition Examination Surveys, who had anti-DM drug therapy information, and were followed up by December 2011 were analyzed. Baseline DM, coronary heart disease (CHD) and heart failure (HF) were defined as a physician-diagnosis of the disease(s). Death from HD was classified using ICD10:I20-I25). Results: Mean (SD) age of 3612 participants was 63.1 (13.02), 83.4% (3056/3612) were under anti-DM therapies, and 20.3% was in metformin monotherapy, 4.9% in metformin combination (MCO), 24.8% in insulin, 45.4% in thiazolidinedione, sulfonylurea, and combinations, and 4.7% in any other antidiabetic drugs therapies. Baseline CHD and HF rates were 11.38% and 9.13%. At the end of follow-up, 1024 died from all-cause (21.86%), and 222 died from HD. Multivariate Cox’s proportional hazard regression analysis indicated that diabetic patients with comorbid HD (CHD and/or HF) had significant higher all-cause mortality than those without. However, these excess mortalities were significantly reduced in patients with metformin therapies than their counterparts without metformin. The hazard ratios (HR, 95%CI) of metformin use versus those without for all-cause mortality was 0.53 (0.38-0.76, p=0.001). Diabetic patients with CHD and with metformin therapies had a significantly lower 10-year all-cause mortality than those without metformin (33% vs. 64%, p In conclusion , metformin significantly increased survival rates from all-cause mortality in diabetic patients with comorbid CHD and/or HF. The mortality risk reduction may be partially explained by an effect of metformin on a reduction of dyslipidemia and insulin resistance.

Purpose of review Cardiac transplant remains the gold standard of care for patients with end-stage heart failure. Unfortunately, due to the limited availability of donor hearts in the United States, not all eligible candidates are able to be transplanted. Since the introduction of mechanical assist devices for the treatment of advanced heart failure, patients gain a significant survival benefit while awaiting transplant. With rapidly evolving technology, it is important to appreciate the advances in the current use of mechanical assist devices. Recent findings Following a comprehensive analysis of novel therapies in end-stage heart failure, there is an enhancement in quality of life and life expectancy following implantation of left ventricular (LV) assist devices (LVADs). When implanted in suitable patients as bridge-to-transplant or 'destination therapy', recipients demonstrate superior outcomes and survival compared with those who remain on optimal medical therapy. Summary The use of LV assist devices (LVADs) as bridge to transplantation has gained popularity over the last decade. It is recognized as an integral treatment modality in end-stage heart failure to those awaiting heart transplantation. When implanted in the appropriately chosen patient, it is superior to medical treatment alone and has shown noninferiority to heart transplantation while allowing for optimal functional status and preservation of end organ function.

As the heart failure population continues to age, the need for definitive therapies such as ventricular assist devices (VADs) to extend life and alleviate suffering from end-stage disease directly increases. The goal of this article is to examine the ethical principles of autonomy, beneficence, non-maleficence, and justice within the context of long-term VAD patients. Survival rates in VAD-implanted patients have improved in parallel with modernization of device design and surgical technique, reaching that of cardiac transplantation at 1 year post-procedure. Even the sickest patients, those once deemed transplant-ineligible, have been proven to benefit from device implantation and in some cases to a point of becoming eligible for cardiac transplantation. Nevertheless, VAD implantation remains a high-risk procedure with in-hospital mortality rates reaching up to 27% post-procedure and requires intensive upkeep even after successful implantation. Furthermore, end-of-life decisions are complicated by consideration of device deactivation in patients who may not die immediately from an otherwise lethal pathophysiology. Ethical considerations in selection of patients, goals of implantation, and length of therapy become important to preserve the efficacy of treatment and maximize resource utilization. Advanced directives, shared decision-making, and multi-disciplinary approach to treatment have been shown to improve outcomes with respect to both survival and quality of life.

According to the Centers for Disease Control, heart failure (HF) remains a pervasive condition with high morbidity and mortality, affecting 5.8 million people in the United States and 23 million worldwide. For patients with refractory end-stage HF, heart transplantation is the "gold standard" for definitive treatment. However, the demand for heart transplantation has consistently exceeded the availability of donor hearts, with approximately 2331 orthotopic heart transplantations performed in the United States in 2015 despite an estimated 100 000 to 250 000 patients with New York Heart Association class IIIB or IV symptoms that are refractory to medical treatment, making such patients potential transplant candidates. As such, the need for mechanical circulatory support (MCS) to treat patients with end-stage HF has become paramount. In this review, we focus on the history, advancements, and current use of durable MCS device therapy in the treatment of advanced heart failure.

Heart failure (HF) is a common clinical syndrome caused by a variety of cardiac diseases. The morbidity and mortality have increased in the last decades. The pathophysiology of HF is exceedingly complex. It has developed from the simplistic model of pump failure to that of a multisystemic disorder that affects not only the cardiovascular system but also the musculoskeletal, neuroendocrine and immune systems. Apart from myocardial hypertrophy, the pathogenetic mechanisms of HF also include deregulation of the neurohormonal system, with disturbance of the balance between sympathetic and parasympathetic tone, and disruption of the rennin-angiotensin-aldosterone system. Activation of neurohormones and pro-inflammatory cytokines has been recognized in HF progression after an initial cardiac injury. It is becoming increasingly apparent that inflammatory mediators play a crucial role in the development of HF. The purpose of this chapter is to give a brief overview of the role of inflammation in heart failure from animal models to clinical disease.

The longer mean survival of oncological patients has led to an increased incidence of chemotherapy-induced cardiomyopathy. Anthracyclines and trastuzumab are the two most commonly implicated agents. Anthracyclines cause irreversible type I cardiomyopathy, where as, trastuzumab causes a potentially reversible type II cardiomyopathy. The most important risk factors are the total cumulative dose and pre-existing cardiovascular disease. MUGA scan and transthoracic echocardiogram are the most commonly used modalities to evaluate left ventricular function. Routine screening must be performed in all patients receiving cardiotoxic drugs. Early detection and treatment is critical for improved long-term cardiovascular prognosis. Patients with cardiomyopathy should be treated with standard heart failure therapy and treatment should be initiated as early as possible. Cardiac resynchronization therapy and heart transplant are viable options for patients with advanced heart failure. There is a great need for more research in this field with goals to develop drugs and protocols with lower cardiotoxicity, which still maintain antitumor efficacy; to develop biomarkers and imaging techniques for early detection of cardiac dysfunction; and to develop better management strategies of patients with cardiomyopathy. Creation of dedicated cardiac-oncology centers is essential for an improved future in this field.

Cardiac transplantation remains the definitive and most highly successful therapy for patients with advanced heart failure who have failed all other therapies. Long-term survival is limited by cardiac allograft vasculopathy, the transplant coronary artery disease, and malignancy. Standard, traditional immunosuppressive agents such as calcineurin inhibitors, anti-proliferative agents, and corticosteroids do little to attenuate cardiac allograft vasculopathy, which, because of its diffuse nature, is usually not amenable to percutaneous or surgical revascularization approaches, and may potentiate the developments of malignancies after cardiac transplantation. Proliferation signal inhibitors block the mammalian target of rapamycin, a critical protein involved in cell proliferation, and inhibit lymphocyte and smooth muscle cell proliferation. This results in inhibition of the alloimmune response and acute cellular rejection, even in the setting of low calcineurin levels. More significantly, they have been shown in several clinical trials to attenuate the progression of cardiac allograft vasculopathy when compared to mycophenolate or azathioprine regimens.

Cardiac transplantation remains the most durable therapy for patients with American College of Cardiology Foundation/American Heart Association stage D advanced heart failure who have exhausted other options, and it is the therapy associated with the best long-term outcomes. One of the major causes