Common Cause Of Heart Failure Research Articles

Estimating the Prevalence of Cardiac Amyloidosis in Old Patients with Heart Failure-Barriers and Opportunities for Improvement: The PREVAMIC Study.

Cardiac amyloidosis (CA) could be a common cause of heart failure (HF). The objective of the study was to estimate the prevalence of CA in patients with HF. Observational, prospective, and multicenter study involving 30 Spanish hospitals. A total of 453 patients ≥ 65 years with HF and an interventricular septum or posterior wall thickness > 12 mm were included. All patients underwent a 99mTc-DPD/PYP/HMDP scintigraphy and monoclonal bands were studied, following the current criteria for non-invasive diagnosis. In inconclusive cases, biopsies were performed. The vast majority of CA were diagnosed non-invasively. The prevalence was 20.1%. Most of the CA were transthyretin (ATTR-CM, 84.6%), with a minority of cardiac light-chain amyloidosis (AL-CM, 2.2%). The remaining (13.2%) was untyped. The prevalence was significantly higher in men (60.1% vs 39.9%, p = 0.019). Of the patients with CA, 26.5% had a left ventricular ejection fraction less than 50%. CA was the cause of HF in one out of five patients and should be screened in the elderly with HF and myocardial thickening, regardless of sex and LVEF. Few transthyretin-gene-sequencing studies were performed in older patients. In many patients, it was not possible to determine the amyloid subtype.

PS-C24-12: HEALTH-RELATED QUALITY OF LIFE, AND OUTCOMES IN ADULTS WITH HEART FAILURE: AGE AND SEX-RELATED DIFFERENCES AND THE ROLE OF HYPERTENSION

Objective: Hypertension is the commonest cause of heart failure. Heart failure is a pandemic and major driver of mortality; limiting disease progression and improving health related quality of life remains the cornerstone of management. There is dearth of information on quality of life in Africans with heart failure. This study examined age and sex related differences and the role of hypertension in the profile, health related quality of life, and clinical outcomes in African adults with heart failure. Design and method: A cross sectional study conducted at the outpatient cardiology clinics of Jos University Teaching Hospital. Two hundred adults with stable heart failure were enrolled using a simple random method. Relevant history, functional class, Charlson comorbidity index were obtained. Physical examination which included electrocardiography, echocardiography, 6 minutes walk distance were done using standard guidelines. Health related quality of life was assessed using the Minnesota living with heart failure questionnaire and graded as good, moderate or poor. Data was analyzed using SPSS version 21. Simple descriptive statistics and multiple logistic regression to determine predictors of moderate and poor quality of life were done. Results: The participants comprised of 104 females and 96 males. More males belonged to higher social class, 21% of the males had health insurance compared to 17% of the females. 48% of the males had atrial fibrillation compared to 33% of the females. About 50% of the participants have heart failure with reduced ejection fraction, there was significant difference in heart failure aetiology below 45 years versus above 45 years in both sexes. The burden of comorbidities was significantly higher in the males and those above 45 years old. There were differences in the individual domain scores of MLHF scores across age groups and sex, the males have a statistically significant poorer quality of life similarly for above 45 year old compared to below 45 year old. The females had higher numbers of hospital admission within the past 12 months and higher hospitalization frequency. functional class 3 or more, 6MWT below 300metres, ejection fraction above 50% and above 6 classes of medication emerged as predictors of moderate/poor MLHF scores in both males and females. Conclusion: This study found significant age and sex-related differences in clinical profile, HRQOL, and clinical outcomes in African adults with HF. Hypertension was the commonest cause of HF. Improved control of hypertension and periodic health related quality of life assessment in patients with HF are advocated to improve outcomes.

Application of Machine Learning for Cardiovascular Disease Risk Prediction

Cardiovascular diseases (CVDs) are a common cause of heart failure globally. The need to explore possible ways to tackle the disease necessitated this study. The study designed a machine learning model for cardiovascular disease risk prediction in accordance with a dataset that contains 11 features which may be used to forecast the disease. The dataset from Kaggle on cardiovascular disease includes approximately 70,000 patient records that were used to determine the outcome. Compared to the UCI dataset, the Kaggle dataset has many more training and validation records. Models created using neural networks, random forests, Bayesian networks, C5.0, and QUEST were compared for this dataset. On training and testing data sets, the results acquired a high accuracy (99.1 percent), which is significantly superior to previous methods. Ahead‐of‐time detection and diagnosis of cardiac disease, as well as better treatment outcomes, are strong possibilities for the suggested prediction model. Additionally, it may help patients better manage their illness or life forms in order to increase their chances of recovery/survival. The result showed greater accuracy and promising signs that machine‐learning algorithms can indeed assist in early identification of the disease and improvement of the treatment outcome.

Undernutrition was a prevalent clinical problem among older adult patients with heart failure in a hospital setting in Northwest Ethiopia.

Undernutrition is a frequently noticed medical problem in patients with heart failure. It is caused by poor nutrient intake, malabsorption, systemic inflammation, neurohumoral activation, oxidative stress, and hypermetabolic state. Undernutrition results in a decrease in the quality of life and the survival rate in patients with heart failure. There is a paucity of documentation on undernutrition among patients with heart failure in sub-Saharan African countries. The study aimed to determine the magnitude and associated factors of undernutrition among older adult patients with heart failure in the hospital setting in Northwest Ethiopia. An institutional-based cross-sectional study was conducted at the University of Gondar Hospital, Northwest Ethiopia, between 1 June 2021 and 31 October 2021. A consecutive sampling method was used to recruit 262 study subjects. A Mini-nutritional assessment-full form (MNA-FL) Questionnaire was used to extract nutritional information among patients with heart failure. Patients with heart failure, who scored MNA-FL score <17, were declared to have undernutrition. The data were entered into EPI Info version 4.6.0.0 and then exported to SPSS version 26 for analysis. Explanatory variables associated with undernutrition in patients with heart failure were analyzed by applying a logistic regression model. A P-value of <0.05 was used to declare a significant association. A total of 262 patients with heart failure were included in the study. The mean age (± SD) of the study subjects was 64.6 (± 9.2) years. Hypertensive heart disease (111/262, 42%) was the most common cause of heart failure. Hypertension was the frequently observed comorbid disease. Based on the MNA-FL score for nutritional status, 75 out of 262 (28.6%, 95% CI: 22.9-34.4%) were undernourished (MNA-FL < 17), while 124 out of 262 (47.3%, CI: 41.5-53.1%) were at risk of undernutrition (MNA-FL = 17-23.5). The remaining 63 out of 262 (24.1%, 95% CI: 18.2-29.8%) study subjects were well nourished (MNA-FL > 24). On a multivariate analysis, patients with severe heart failure (New York Heart Association (NYHA) functional class III/IV) (AOR = 4.287, CI: 2.012-9.134, P-value < 0.001), with a duration of illness of 3-5 years (AOR = 3.225, CI: 1.138-9.137, P-value = 0.028), with a duration of illness of >5 years (AOR = 4.349, CI: 1.592-11.879, P-value = 0.001), presence of comorbidities (AOR = 2.29, CI: 1.06-4.96, P-value = 0.036), who underwent treatment with loop diuretics (AOR = 2.983, CI: 1.407-6.326, P-value = 0.040), and who reside in a rural area (AOR = 5.119, CI: 2.481-10.560, P-value < 0.001) were at risk of developing undernutrition. Undernutrition was a significant clinical problem in older patients with heart failure. Nutritional interventions should be prioritized for patients with chronic and severe heart failure.

A risk model developed based on necroptosis to assess progression for ischemic cardiomyopathy and identify possible therapeutic drugs.

Object: Ischemic cardiomyopathy (ICM), with high morbidity and mortality, is the most common cause of heart failure. Cardiovascular remodeling secondary to chronic myocardial ischemia is the main cause of its progression. A recently identified type of programmed cell death called necroptosis is crucial in the development of various cardiovascular diseases. However, the function role of necroptosis in cardiac remodeling of ICM has not been elucidated. Our study aimed to screen for genes associated with necroptosis and construct a risk score to assess the progression and evaluate the prognosis of ICM patients, and further to search for potentially therapeutic drugs. Methods: The gene expression profiling was obtained from the GEO database. LASSO regression analysis was used to construct necroptosis-related gene signatures associated with ICM progression and prognosis. TF-gene and miRNA-gene networks were constructed to identify the regulatory targets of potential necroptosis-related signature genes. Pathway alterations in patients with high necroptosis-related score (NRS) were analyzed by GO, KEGG, GSEA analysis, and immune cell infiltration was estimated by ImmuCellAI analysis. CMap analysis was performed to screen potential small molecule compounds targeting patients with high NRS. Independent risk analyses were performed using nomograms. Results: Six necroptosis-related signature genes (STAT4, TNFSF10, CHMP5, CHMP18, JAK1, and CFLAR) were used to define the NRS, with areas under the ROC curves of 0.833, 0.765, and 0.75 for training test, test set, and validation set, respectively. Transcription factors FOXC1 and hsa-miR-124-3p miRNA may be regulators of signature genes. Patients with higher NRS have pathway enriched in fibrosis and metabolism and elevated nTreg cells. AZD-7762 may be an effective drug to improve the prognosis of patients with high NRS. A feature-based nomogram was constructed from which patients could derive clinical benefit. Conclusion: Our results reveal 6 necroptosis gene signatures that can evaluate the progression and prognosis of ICM with high clinical value, and identify potential targets that could help improve cardiovascular remodeling.

Safety and efficacy of acupuncture for anxiety and depression in patients with heart failure: A protocol for systematic review and meta-analysis.

In recent years, with the increase of patients with coronary heart disease, the number of patients with heart failure (HF) has also gradually increased. Coronary heart disease is one of the most common causes of HF. Anxiety and depression are frequent psychological disorders in patients with HF. Studies have shown that anxiety and depression can affect the quality of life of patients with HF, and can increase hospitalization and mortality. Conventional pharmacotherapy and psychotherapy have certain limitations. Acupuncture has therapeutic effects on heart disease, anxiety and depression, and has been widely used to relieve symptoms in patients with HF. This protocol aims to evaluate the safety and efficacy of acupuncture for anxiety and depression in patients with HF. We will search the following databases: PubMed, Web of Science, Springer Cochrane Library, EMBASE, MEDLINE, WHO international clinical trials registry platform, China National Knowledge Infrastructure database, Wan Fang database, Chinese scientific journal database and Chinese Biomedical Literature Database. The databases will be searched from initiate to October 1, 2022. Two reviewers will screen and document eligible studies based on inclusion and exclusion criteria. Two reviewers will independently perform data analysis and bias risk assessment. Review Manager version 5.4 software will be used for meta-analysis. This study will explore the efficacy and safety of acupuncture for anxiety and depression in patients with HF. The results of this study will provide high-quality evidence for evaluating the safety and efficacy of acupuncture for anxiety and depression in patients with HF.

Abstract 11026: Proteomic Signatures of Ischemic and Non-Ischemic Heart Failure in a Community Cohort

Introduction: Coronary disease is the most common cause of heart failure (HF). HF is classified as ischemic (IHF) or non-ischemic (NIHF) based on this etiology. IHF and NIHF have distinct mechanisms not accounted for by ejection fraction (EF) and an improved understanding of the differences could drive the discovery of novel therapeutic targets. We therefore sought to identify proteomic signatures between IHF and NIHF. Methods: Proteomic profiling using the SomaScan®1.7K was performed using plasma samples from HF patients in a community cohort (Rochester Epidemiology Project, 2003-2012). IHF was defined by prior myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft, or obstructive disease in at least 1 vessel on coronary angiography. We compared the protein expression levels between IHF and NIHF using t-test and applied the Benjamini-Hochberg false-discovery rate (FDR) procedure for multiple comparisons. We explored pathway analysis for functional annotations using the biological process component of the Gene Ontology Resource (Panther 17v). Results: Among 1,388 patients, there were 518 IHF patients (age: 75±12years, 39.4% female, NYHA Class III/IV: 72.5%, EF:45±15%), and 870 NIHF patients (age: 75±14years, 53.6% female, NYHA Class III/IV: 66.9%, EF:49±17%). Among 7335 plasma proteins quantified, 63 unique proteins (FDR &lt; 0.05) were differentially expressed between IHF and NIHF. Thirty-seven proteins including Troponin-I and T, and Myoglobin showed increased expression in IHF compared to NIHF and 26 including IGFBP-3 showed decreased expression. Pathophysiologic pathways including angiogenesis, coagulation, and lipid metabolism were represented in IHF, while inflammation and remodeling signaling pathways were dominant in relation to NIHF. Conclusions: High-throughput proteomic techniques are able to delineate IHF versus NIHF patients based on distinct biomarkers and pathophysiologic processes.

Abstract 11069: Evaluation for Ischemic Cardiomyopathy After Heart Failure Diagnosis is Associated With Reduced Mortality in a Safety-Net Setting

Introduction: Ischemic cardiomyopathy is a common cause of heart failure (HF). Many commercially insured HF patients are not evaluated for ischemia, but rates of testing in a safety net setting have not been investigated, and the effect of testing on mortality is not clear. Methods: We developed an EHR cohort of individuals with HF by ICD9 or 10 code in San Francisco’s municipal health system during 2001-2019. Invasive coronary angiography, nuclear stress, and coronary CT angiography were considered as ischemic testing. Proportions tested and adjusted relative risks [ARR] for testing were adjusted for age, sex, diabetes, hypertension, and tobacco use. To estimate the effect of testing on mortality, we created a “target trial” of patients with incident HF without known CAD using propensity score models. Results: Out of 15,558 individuals with HF, 4,215 (27.1%) ever underwent ischemic testing, without increase over time (p=0.33). Excluding those with prior testing, 2,483/13,821 (18.0%) had testing at a median 25 days after HF diagnosis (IQR 0-417). Groups less likely to receive testing included women (ARR 0.89, 95%CI 0.82-0.96; p=0.003), unstably housed individuals (ARR 0.45, 95%CI 0.37 to 0.54, p&lt;0.0001), people with HIV (ARR 0.67, 95%CI 0.57-0.79, p&lt;0.0001), and methamphetamine users (ARR 0.77, 95%CI 0.69-0.86; p&lt;0.0001). Those hospitalized for HF were more likely to be tested (ARR 2.21, 95% CI 2.05-2.39; p&lt;0.0001). Testing within 30 days was associated with a 4% absolute reduction in mortality (95%CI -6.5 to -1.6%; p&lt;0.001) independent of hospitalization. Testing within 30 days and ever were associated with 22% and 27% lower mortality hazard, respectively (Figure). Conclusions: In a municipal health system in San Francisco, women, people with HIV, without stable housing, and methamphetamine users were less likely to receive ischemic testing. Ischemic testing was associated with improved survival. Ischemic testing should be considered for everyone with HF.

Irisin and ALCAT1 mediated aerobic exercise-alleviated oxidative stress and apoptosis in skeletal muscle of mice with myocardial infarction.

Skeletal muscle in patients with heart failure (HF) exhibits altered structure, function and metabolism. Myocardial infarction (MI) is the most common cause of HF. Oxidative stress and cell apoptosis are involved in the pathophysiology of MI/HF-induced skeletal muscle atrophy. It is well recognized that aerobic exercise (AE) could prevent skeletal muscle atrophy after MI, but the underlying mechanism and molecular targets are still not fully clarified. In this study, Fndc5-/- and Alcat1-/- mice were used to establish the MI model and subjected to six weeks of moderate-intensity AE. C2C12cells were treated with H2O2 and recombinant human Irisin (rhIrisin), or transduced with a lentiviral vector to mediate the overexpression of ALCAT1 (LV-Alcat1). Results showed that MI reduced Irisin expression and antioxidant capacity of skeletal muscle, increased ALCAT1 expression, induced protein degradation and cell apoptosis, which were partly reversed by AE; Knockout of Fndc5 further aggravated MI-induced oxidative stress and cell apoptosis in skeletal muscle, and partly weakened the beneficial effects of AE. In contrast, knockout of Alcat1 reduced MI-induced oxidative stress and cell apoptosis and strengthened the beneficial effects of AE. rhIrisin and AICAR intervention inhibited ALCAT1 expression, oxidative stress and cell apoptosis, which induced by H2O2 or LV-Alcat1 in C2C12cells. These findings reveal that AE could alleviate the levels of oxidative stress and apoptosis in skeletal muscle following MI, partly via up-regulating Irisin and inhibiting ALCAT1 expression.

Paediatric heart failure in Uyo: A retrospective analysis

Background/Aim: Paediatric heart failure is a condition that continues to present challenges in management in our environment especially in its treatment and outcomes hence the aim of this study.Materials and Methods: A retrospective analysis of the case notes of all children who were diagnosed and managed for heart failure from January 2019 – October 2021 was undertaken. Data obtained included age, sex, presenting features, primary diagnosis, treatment modalities, duration ofhospital stay and outcomes.Results: A total of 2226 children were admitted over the study period with 67 children diagnosed with heart failure giving a prevalence rate of 3% although only 47 case notes could be retrieved giving a case retrieval rate of 70%. There were 26 (55.3%) males and 21 (44.7%) females (M:F ratio1.2: 1). Mean age of patients was 32.6 months (±52.23) with 28 (59.6%) of them being infants. Bronchopneumonia was the commonest cause of heart failure 31(65.9%) either singly or in combination with acyanotic congenital heart disease followed by severe anaemia in 14 (29.8%). Average duration of hospital stay was 6.9days (±5.08) and average cost of admission was N13,266. Twenty-three patients were discharged (48.9%), while 10 (21.3%) left against medical advice, 2 absconded (4.3%) while 12 (25.3%) died.Conclusion: Heart failure remains an important cause of morbidity and mortality in children in our environment arising from largely preventable causes. Urgent steps such as patient care giver education, immunization and screening for congenital heart disease are needed to reduce its effect on children in our environment.

Primary cardiomyopathies in childhood: clinical and diagnostic features (literature review)

Primary cardiomyopathies in childhood are a rare but serious disease that is a common cause of heart failure and the most common reason for heart transplantation in children over one year of age. Over the past decades, the diagnosis of cardiomyopathy has advanced from traditional clinical imaging methods to new genetic and imaging techniques. The article presents a review of the literature data on the modern classification of primary pediatric cardiomyopathies and the features of the clinical course and imaging, which is an integral part of the diagnosis based on the primary morphofunctional phenotype.

Genotype Complements the Phenotype: Identification of the Pathogenicity of an LMNA Splice Variant by Nanopore Long-Read Sequencing in a Large DCM Family.

Dilated cardiomyopathy (DCM) is a common cause of heart failure (HF) and is of familial origin in 20–40% of cases. Genetic testing by next-generation sequencing (NGS) has yielded a definite diagnosis in many cases; however, some remain elusive. In this study, we used a combination of NGS, human-induced pluripotent-stem-cell-derived cardiomyocytes (iPSC-CMs) and nanopore long-read sequencing to identify the causal variant in a multi-generational pedigree of DCM. A four-generation family with familial DCM was investigated. Next-generation sequencing (NGS) was performed on 22 family members. Skin biopsies from two affected family members were used to generate iPSCs, which were then differentiated into iPSC-CMs. Short-read RNA sequencing was used for the evaluation of the target gene expression, and long-read RNA nanopore sequencing was used to evaluate the relevance of the splice variants. The pedigree suggested a highly penetrant, autosomal dominant mode of inheritance. The phenotype of the family was suggestive of laminopathy, but previous genetic testing using both Sanger and panel sequencing only yielded conflicting evidence for LMNA p.R644C (rs142000963), which was not fully segregated. By re-sequencing four additional affected family members, further non-coding LMNA variants could be detected: rs149339264, rs199686967, rs201379016, and rs794728589. To explore the roles of these variants, iPSC-CMs were generated. RNA sequencing showed the LMNA expression levels to be significantly lower in the iPSC-CMs of the LMNA variant carriers. We demonstrated a dysregulated sarcomeric structure and altered calcium homeostasis in the iPSC-CMs of the LMNA variant carriers. Using targeted nanopore long-read sequencing, we revealed the biological significance of the variant c.356+1G>A, which generates a novel 5′ splice site in exon 1 of the cardiac isomer of LMNA, causing a nonsense mRNA product with almost complete RNA decay and haploinsufficiency. Using novel molecular analysis and nanopore technology, we demonstrated the pathogenesis of the rs794728589 (c.356+1G>A) splice variant in LMNA. This study highlights the importance of precise diagnostics in the clinical management and workup of cardiomyopathies.

Soluble ST2 in coronary artery disease: Clinical biomarkers and treatment guidance.

The IL-33/ST2 L signaling pathway is involved in the pathophysiological processes of several diseases and mainly exerts anti-inflammatory and antifibrotic effects. Soluble suppression of tumorigenicity 2 (sST2), which serves as a competitive inhibitory molecule of this pathway, is a member of the interleukin (IL)-1 family, a decoy receptor for IL33, thought to play a role in cardiac remodeling and the inflammatory process. However, the association between sST2 and coronary artery disease (CAD), one of the most common causes of heart failure, is still being explored. We therefore reviewed the research on sST2 in the field of CAD, including reflecting the atherosclerosis burden, predicting no-reflow, predicting prognosis, responding to myocardial remodeling, and guiding management, hoping to provide cardiologists with new perspectives.

Heart transplantation in children and adults with Down syndrome: A single centre experience.

In recent years, rapid advances in cardiac surgery and changes in attitude towards patients with cognitive disability have led to these patients receiving cardiac transplantation. This is a retrospective report describing the experience of four patients with Down Syndrome who received heart transplantation in a single institution. Anthracycline-induced cardiomyopathy was the most common cause of heart failure in this group (3/4). Two patients were bridged to transplantation, one by using a combination of extra-corporeal membrane oxygenation and biventricular assist device and the other by using a durable implantable left ventricular assist device. All the four patients are alive with the longest surviving patient 17 years after transplantation. Against strong hypothetical predictions, we observed no propensity for the development of post-transplant infections or lymphoproliferative disorders. Down Syndrome should not be the sole contraindication to heart transplantation. The decision for transplantation should be on a case-by-case basis provided adequate social support is in place.

STUDY OF CLINICAL AND ECHOCARDIOGRAPHIC PROFILE IN PATIENTS OF DILATED CARDIOMYOPATHY

Objective: Dilated cardiomyopathy (DCM) is the third most common cause of heart failure (HF) and is the most common cardiomyopathy. The present study was undertaken with the aim to study the different clinical presentations of dilated cardiomyopathy, to correlate echocardiography findings with different clinical presentations and to find out the variables which determine the poor outcomes.&#x0D; &#x0D; Methods: This prospective observational study was conducted in the Department of General Medicine of MKCG Medical College and Hospital, Berhampur, Odisha, India from November 2019 to November 2021. Fifty cases of dilated cardiomyopathy (28 males &amp; 22 females), diagnosed on clinical and echocardiography criteria in the Department of General Medicine and Cardiology were selected for the study.&#x0D; &#x0D; Results: Out of 50 cases, there were 28(56%) males and 22(44%) females giving male to female ratio 1.27:1. Forty (80%) were idiopathic. Dyspnea was most common presenting clinical feature in 43(86%) cases. In echo study, maximum number of cases (n=21, 42%) were having ejection fraction (EF) in the range of 36-40% and maximum number of cases (n=26, 52%) had severe fractional shortening (FS).&#x0D; &#x0D; Conclusion: DCM is one of the commonest causes of heart failure and is most common type of cardiomyopathy found in middle aged and elderly male population. Biventricular failure followed by left ventricular failure was the most frequent clinical presentation. Early identification and treatment are very essential to improve cardiac function and alleviate patient symptomology.

Prevalence, risk factors, and survival associated with pulmonary hypertension and heart failure among patients with underlying coronary artery disease: a national prospective, multicenter registry study in China.

Background:Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH.Methods:Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded.Results:One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH.Conclusions:PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients.Trial Registration:ClinicalTrials.gov, NCT02164526.

Abstract P3030: Fundc1 Mediated Mitochondrial Protein Import As A Novel Mechanism Exacerbating Dilated Cardiomyopathy

Background: Dilated cardiomyopathy (DCM) is a common cause of heart failure and an indication for heart transplantation worldwide. FUN14 Domain Containing 1 (FUNDC1), a canonical mitophagy receptor and mitochondria-associated ER membranes (MAMs) protein, plays an essential role in ischemic heart disease. However, the role of FUNDC1 in DCM remains unidentified. The current study attempted to clarify whether and how FUNDC1 regulates DCM development. Methods: Cardiomyocyte-specific F UNDC 1 gene knockout (CM-FUNDC1 KO) mice were generated to study the impact and potential mechanisms of FUNDC1 in the heart. Mitochondria were isolated from heart tissues, primary mouse neonatal/adult cardiomyocytes, or H9C2 cell lines to probe the role of FUNDC1 in mitochondrial protein import (MPI). Results: All CM-FUNDC1 KO mice developed severe DCM spontaneously and died before 15 months old. The expression of MPI-associated proteins was significantly upregulated in the hearts of CM-FUNDC1 KO mice. Experiments with purified mitochondria demonstrated that MPI efficiency was enhanced by CM-FUNDC1 KO, whereas reduced by FUNDC1 overexpression in an autophagy-independent fashion. We further identified that FUNDC1 selectively downregulated the TIM23 complex without altering other MPI translocases (e.g., TOM20, TIM22 complexes). Downregulation of subunits of TIM23 complex partly reversed the FUNDC1 KO-induced MPI enhancement. Importantly, we demonstrated that FUNDC1 selectively inhibited the import of nuclear gene-encoded respiratory subunits on complex I, IV but not on complex II, III, V or mitochondrial gene-encoded subunits. Finally, FUNDC1 deleted cells exhibited enlarged cell size, retarded cell growth, impaired oxygen consumption rate, and increased mitochondrial superoxide level. All of these phenomena were partly reversed by silence TIM23 complex or reproduced by TIM23 complex overexpression. Conclusions: We demonstrate for the first time that: 1) MPI system plays an important role in the progress of DCM; 2) FUNDC1 is a novel negative regulator of MPI via TIM23 pathway; and 3) FUNDC1 is a promising therapeutic target for DCM.

Cardioprotection of Klotho against myocardial infarction-induced heart failure through inducing autophagy

Myocardial infarction (MI) is the most common cause of heart failure (HF) worldwide. The aim of this study was to investigate the role of Klotho in cardiac function and remodeling as well as its underlying mechanism in mice with MI-induced HF. For in vivo analyses, MI or sham MI were established in C57BL/6 mice. For in vitro analyses, the H9C2 cells were used to establish a model of oxygen glucose deprivation (OGD). The In vivo and in vitro models were treated with or without Klotho. 3-methyladenine (3-MA) was used to inhibit autophagy in MI mice and H9C2 cells. Cardiac function, cardiac fibrosis, cardiomyocyte autophagy, inflammatory cytokines and myocardial apoptosis were measured. Our results revealed that Klotho significantly improved cardiac function and remodeling, reduced cardiac fibrosis, and suppressed the levels of myocardial inflammatory factors and apoptosis in MI-induced HF model. Klotho enhanced autophagy in cardiomyocytes and inhibited PI3K/AKT/mTOR signaling pathway in the mouse model of MI. Similar observations were made in the OGD model after treatment with Klotho. However, the cardioprotective effects of Klotho was significantly suppressed by 3-MA. Our data indicate that Klotho exerts its cardioprotective effects against MI-induced HF by inducing autophagy through the inhibition of PI3k/AKT/mTOR signaling pathway.

Understanding heart failure with preserved ejection fraction

Poppy Brooks looks at how to diagnose and manage this common cause of heart failure

Alcohol Intake in Patients With Cardiomyopathy and Heart Failure: Consensus and Controversy.

Alcohol is often cited to be a common cause of cardiomyopathy and heart failure. However, in most available population-based studies, a modest-to-moderate alcohol consumption has been associated with favorable effects on the cardiovascular system, including a lowered risk of heart failure, compared with no alcohol consumption. Available genetic epidemiological data have not supported a causal association between alcohol consumption and heart failure risk, suggesting that alcohol may not be a common cause of heart failure in the community. Data linking alcohol intake with cardiomyopathy risk are sparse, and the concept of alcoholic cardiomyopathy stems mainly from case series of selected patients with dilated cardiomyopathy, where a large proportion reported a history of excessive alcohol intake. This state-of-the-art paper addresses the current knowledge of the epidemiology of alcoholic cardiomyopathy and the role of alcohol intake in patients with non-alcohol-related heart failure. It also offers directions to future research in the area. The review questions the validity of current clinical teaching in the area. It is not well known how much alcohol is needed to cause disease, and the epidemiological pathways linking alcohol consumption to cardiomyopathy and heart failure are not well understood. Until more evidence becomes available, caution is warranted before labeling patients as having alcoholic cardiomyopathy due to a risk of neglecting other contributors, such as genetic causes of cardiomyopathy. In non-alcohol-related heart failure, it is unknown whether total abstinence is improving outcomes (compared with moderate drinking). Ideally, randomized clinical trials are needed to answer this question.