Common Cause Of Heart Failure Research Articles

Percutaneous Coronary Intervention Versus Optimal Medical Therapy for Severe Ischemic Left Ventricular Systolic Dysfunction

Coronary artery disease is the most common cause of heart failure, which is the leading cause of cardiovascular-related death worldwide. There are insufficient data to make strong recommendations for percutaneous coronary intervention (PCI) in patients with severe ischemic left ventricular systolic dysfunction (LVSD). In that context, we performed a meta-analysis to compare the outcomes of PCI with those of optimal medical therapy alone in patients with severe ischemic LVSD. A systematic search was conducted in PubMed, EMBASE, and ClinicalTrials.gov from inception to December 2023. Our outcome of interest was all-cause mortality in patients undergoing PCI vs medical therapy. We used random effects models to aggregate data and to calculate pooled incidence and relative risk with 95% CIs. Four studies including 2 randomized controlled trials with 2080 patients (PCI, 1082; optimal medical therapy, 998) were included. All-cause mortality did not differ significantly between the groups: 168 patients (15.5%) in the PCI group vs 200 patients (20.0%) in the optimal medical therapy group (relative risk, 0.88; 95% CI, 0.75-1.09; P=.25). In conclusion, the available evidence indicates that PCI does not improve all-cause mortality in patients with severe LVSD without lifestyle-limiting anginal symptoms. Further data are needed to identify subgroups of patients better served by each modality.

Comprehensive bioinformatics analytics and in vivo validation reveal SLC31A1 as an emerging diagnostic biomarker for acute myocardial infarction.

Globally, Acute Myocardial Infarction (AMI) is a common cause of heart failure (HF), which has been a leading cause of mortality resulting from non-communicable diseases. On the other hand, increasing evidence suggests that the role of energy production within the mitochondria strongly links to the development and progression of heart diseases, while Cuproptosis, a newly identified cell death mechanism, has not yet been comprehensively analyzed from the aspect of cardiovascular medicine. 8 transcriptome profiles curated from the GEO database were integrated, from which a diagnostic model based on the Stacking algorithm was established. The efficacy of the model was evaluated in a multifaced manner (i.e., by Precision-Recall curve, Receiver Operative Characteristic curve, etc.). We also sequenced our animal models at the bulk RNA level and conducted qPCR and immunohistochemical staining, with which we further validated the expression of the key contributor gene to the model. Finally, we explored the immune implications of the key contributor gene. A merged machine learning model containing 4 Cuproptosis-related genes (i.e., PDHB, CDKN2A, GLS, and SLC31A1) for robust AMI diagnosis was developed, in which SLC31A1 served as the key contributor. Through in vivo modeling, we validated the aberrant overexpression of SLC31A1 in AMI. Besides, further transcriptome analysis revealed that its high expression was correlated with significant potential immunological implications in the infiltration of many immune cell types, especially monocyte. We constructed an AMI diagnostic model based on Cuproptosis-related genes and validated the key contributor gene in animal modeling. We also analyzed the effects on the immune system for its overexpression in AMI.

Single-Cell RNA Sequencing Reveals Cardiac Fibroblast-Specific Transcriptomic Changes in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common cause of heart failure, with a complex aetiology involving multiple cell types. We aimed to detect cell-specific transcriptomic alterations in DCM through analysis that leveraged recent advancements in single-cell analytical tools. Single-cell RNA sequencing (scRNA-seq) data from human DCM cardiac tissue were subjected to an updated bioinformatic workflow in which unsupervised clustering was paired with reference label transfer to more comprehensively annotate the dataset. Differential gene expression was detected primarily in the cardiac fibroblast population. Bulk RNA sequencing was performed on an independent cohort of human cardiac tissue and compared with scRNA-seq gene alterations to generate a stratified list of higher-confidence, fibroblast-specific expression candidates for further validation. Concordant gene dysregulation was confirmed in TGFβ-induced fibroblasts. Functional assessment of gene candidates showed that AEBP1 may play a significant role in fibroblast activation. This unbiased approach enabled improved resolution of cardiac cell-type-specific transcriptomic alterations in DCM.

Characterization of Non-Ischemic Dilated Cardiomyopathy in a Native Tanzanian Cohort: MOYO Study.

Non-ischemic dilated cardiomyopathy (NIDCM) is a common cause of heart failure with progressive tendency. The disease occurs in one in every 2,500 individuals in the developed world, with high morbidity and mortality. However, detailed data on the role of NIDCM in heart failure in Tanzania is lacking. To characterize NIDCM in a Tanzanian cohort with respect to demographics, clinical profile, imaging findings and management. Characterization of non-ischemic dilated cardioMyOpathY in a native Tanzanian cOhort (MOYO) is a prospective cohort study of NIDCM patients seen at the Jakaya Kikwete Cardiac Institute. Patients aged ≥18 years with a clinical diagnosis of heart failure, an ejection fraction of ≤45% on echocardiography and no evidence of ischemia were enrolled. Clinical data, echocardiography, electrocardiography (ECG), coronary angiography and stress ECG information were collected from February 2020 to March 2022. Of 402 patients, n = 220 (54.7%) were males with a median (IQR) age of 55.0 (41.0, 66.0) years. Causes of NIDCM were presumably hypertensive n = 218 (54.2%), idiopathic n = 116 (28.9%), PPCM n = 45 (11.2%), alcoholic n = 10 (2.5%) and other causes n = 13 (3.2%). The most common presenting symptoms were dyspnea n = 342 (85.1%), with the majority of patients presenting with New York Heart Association (NYHA) Class III n = 195 (48.5%). The mean (SD) left ventricular ejection fraction (LVEF) was 29.4% (±7.7), and severe systolic dysfunction (LVEF <30%) was common n = 208 (51.7%). Compared with other forms of DCM, idiopathic DCM patients were significantly younger, had more advanced NYHA class (p < 0.001) and presented more often with left bundle branch block on ECG (p = 0.0042). There was suboptimal use of novel guidelines recommended medications ARNI n = 10 (2.5%) and SGLT2 2-inhibitors n = 2 (0.5%). In our Tanzanian cohort, the majority of patients with NIDCM have an identified underlying cause, and they present at late stages of the disease. Patients with idiopathic DCM are younger with more severe disease compared to other forms of NIDCM.

Epidemiology of heart failure in rural Chhattisgarh, India.

Background Cardiovascular diseases, including heart failure (HF), are leading causes of death and disability in India. However, most studies in India only include urban populations or rural regions with improved access and may not represent the poorest patients or regions. We studied the epidemiology of HF patients admitted to a secondary care hospital in rural Chhattisgarh, India. Methods We did a retrospective chart review of patients hospitalized with HF in 2018 to obtain their demographic data and risk factors for developing HF. We reviewed echocardio-grams to assign patients to their most probable HF category. Results We studied 88 HF patients with a mean age of 42 years including 55 (62.5%) women. The most common categories of HF were cardiomyopathy (36.8%), rheumatic heart disease (RHD; 25.3%) and right heart failure (RHF; 18.4%). Prior tuberculosis was more prevalent in patients with RHF compared with other types of HF (43.8% v. 13.9%). Conclusions HF patients in this study from rural central India were young and predominantly women. Cardiomyopathy, RHD and RHF due to past tuberculosis were common causes of HF in this population. Further studies are needed to expand upon these single centre findings to better understand the risk factors and outcomes of HF among the rural poor.

Waitlist Outcomes in Candidates With Rare Causes of Heart Failure After Implementation of the 2018 French Heart Allocation Scheme.

In 2018, an algorithm-based allocation system for heart transplantation (HT) was implemented in France. Its effect on access to HT of patients with rare causes of heart failure (HF) has not been assessed. In this national study, including adults listed for HT between 2018 and 2020, we analyzed waitlist and posttransplant outcomes of candidates with rare causes of HF (restrictive cardiomyopathy [RCM], hypertrophic cardiomyopathy, and congenital heart disease). The primary end point was death on the waitlist or delisting for clinical deterioration. Secondary end points included access to HT and posttransplant mortality. The cumulative incidence of waitlist mortality estimated with competing risk analysis and incidence of transplantation were compared between diagnosis groups. The association of HF cause with outcomes was determined by Fine-Gray or Cox models. Overall, 1604 candidates were listed for HT. At 1 year postlisting, 175 patients met the primary end point and 1040 underwent HT. Candidates listed for rare causes of HF significantly differed in baseline characteristics and had more frequent score exceptions compared with other cardiomyopathies (31.3%, 32.0%, 36.4%, and 16.7% for patients with hypertrophic cardiomyopathy, RCM, congenital heart disease, and other cardiomyopathies). The cumulative incidence of death on the waitlist and probability of HT were similar between diagnosis groups (P=0.17 and 0.40, respectively). The adjusted risk of death or delisting for clinical deterioration did not significantly differ between candidates with rare and common causes of HF (subdistribution hazard ratio (HR): hypertrophic cardiomyopathy, 0.51 [95% CI, 0.19-1.38]; P=0.18; RCM, 1.04 [95% CI, 0.42-2.58]; P=0.94; congenital heart disease, 1.82 [95% CI, 0.78-4.26]; P=0.17). Similarly, the access to HT did not significantly differ between causes of HF (hypertrophic cardiomyopathy: HR, 1.18 [95% CI, 0.92-1.51]; P=0.19; RCM: HR, 1.19 [95% CI, 0.90-1.58]; P=0.23; congenital heart disease: HR, 0.76 [95% CI, 0.53-1.09]; P=0.14). RCM was an independent risk factor for 1-year posttransplant mortality (HR, 2.12 [95% CI, 1.06-4.24]; P=0.03). Our study shows equitable waitlist outcomes among HT candidates whatever the indication for transplantation with the new French allocation scheme.

Optimisation of conservative treatment of patients with severe heart failure by using hemosorption

Background. Heart failure (HF) is a complex cardiac pathology that is the main cause of hospitalisation among adults and is characterised by a high mortality. Dilated cardiomyopathy (DCM) is the most common cause of HF, and it can be fatal within a few years after the first symptoms appear. Many patients with HF remain refractory to medical therapy, despite its constant development and improvement. The study aims to compare the effectiveness of conservative treatment of patients with severe HF that occurred on the background of DCM using drug therapy and its combination with a course of hemosorption (HS). Materials and methods. We analysed treatment outcomes in 30 patients with severe HF against DCM (New York Heart Association class III–V, left ventricular ejection fraction (LV EF) &lt; 30 %). Patients in group 1 (n = 13; N-terminal fragment of brain natriuretic peptide precursor (NT-pro BNP) 4,546.23 ± ± 3,265.01 pg/ml; LV EF 16.77 ± 2.92 %; LV end-diastolic volume (EDV) 261.31 ± 60.60 ml, LV end-systolic volume (ESV) 214.85 ± 49.44 ml) received drug therapy according to local protocols. In group 2 (n = 17; NT-pro BNP 3,974.49 ± 3,550.17 pg/ml; LV EF 18.18 ± 4.36 %; LV EDV 261.12 ± 79.96 ml, LV ESV 212.06 ± 71.67 ml), medical treatment was supplemented with a course of 3 HS procedures using granular deligandizing hemosorbent. Results. Patients in both study groups noted an improvement in well-being and a decrease in the severity of symptoms. The level of NT-pro BNP decreased to 2,609.92 ± 1,465.14 pg/ml (p &lt; 0.01) in group 1 and to 975.35 ± 511.55 pg/ml (p &lt; 0.05) in group 2. LV EF increased to 22.77 ± 4.69 % and 26.76 ± 5.02 %, respectively, in the groups (p &lt; 0.01). In patients of group 1, LV EDV and LV ESV changed to 262.22 ± 40.92 ml and 211.33 ± 35.22 ml, respectively. In group 2, there was a significant decrease in LV EDV to 228.94 ± 73.16 ml and LV ESV to 170.88 ± 60.28 ml (p &lt; 0.01). Conclusions. The use of HS in combination with drug therapy for severe HF on the background of DCM improves the clinical status of patients and LV systolic function.

Public Awareness of Heart Failure Among the Population of Makkah City, Saudi Arabia: A Cross-Sectional Study.

Background Heart failure (HF), a major public health problem worldwide, is a complex clinical syndrome caused by structural or functional heart disorders occurring when the heart cannot supply sufficient blood to the body. The most common cause of HF is impairment of the left ventricle. Public awareness of HF is critical for controlling the disease burden, recognizing disease severity, and determining its prognosis. Therefore, this study assesses the awareness and perception of HF among the population in Makkah City, Saudi Arabia. Methods A cross-sectional study was conducted among 1,053 participants over 18 years of age who lived in Makkah City between October 2022 and February 2023. Participants were randomly selected and recruited using a validated online questionnaire. Results Of the participants, 62.4% had heard of HF, and the majority (59.5%) correctly identified it. Regarding the etiology of the disease, about 50.6% indicated that it was related to the aging process, and 82.9% indicated it was related to high blood pressure. Only 24.1% of participants correctly recognized HF symptoms; most defined the symptoms as general heart disease. Moreover, 51.6% of participants agreed that the current HF medications can reduce deaths from HF and improve quality of life. However, most respondents disagreed that HF drugs can prevent the onset of HF. Conclusion The findings emphasize the need for more awareness programs to raise the public awareness about HF and effectively guide the population to more reliable sources that provide evidence-based information about the disease.

Effects of pericyte and smooth muscle specific knock-out of CXCL12 on cardiac function after myocardial ischemia in mice

Abstract Introduction Ischemic cardiomyopathy as a result of myocardial infarction represents one of the most common causes of heart failure (1). The C-X-C motif chemokine ligand 12 (CXCL12) and its receptor CXCR4 facilitate cardiac repair after myocardial ischemia (MI) and play fundamental roles in cardiovascular development (2). However, the cell- and tissue-specific actions of CXCL12 are poorly understood, limiting the introduction of targeted therapies. Here, we aimed to examine the role of pericyte and smooth muscle cell-specific CXCL12 expression on myocardial function after MI. Methods We generated a smooth muscle protein 22-alpha-Cre and a pericyte protein NG2-Cre driven mouse model to ablate CXCL12 specifically in smooth muscle cells (SM22-Cre x CXCL12flox/flox) and in pericytes (NG2-Cre x CXCL12flox/flox). Genotyping was performed using ear hole biopsy by PCR. Hearts were analysed morphologically by histology and immunofluorescence. Cardiac function and dimensions of the wall thicknesses and cardiac cavities were determined by echocardiography. Myocardial infarction was induced in the animals and cardiac function was further investigated 28 days after MI. Results In immunofluorescence, we found that CXCL12 is highly expressed in SM22+ smooth muscle cells and in cells surrounding arterial blood vessels (3). NG2-CXCL12-/- mice did not show increased mortality, they behaved inconspicuously and no obvious developmental defects could be detected. Echocardiographic analysis of cardiac function in NG2-Cre x CXCL12flox/flox mice without infarction showed no significant difference in left ventricular (LV) performance and no evidence of abnormal geometry of the ventricles compared with controls. Assessment of SM22-Cre x CXCL12flox/flox mice after MI revealed reduced ejection fraction (EF) (29.0%±9.7 vs. 40.0%±8.1; n=10; p=0.027) and stroke volume (SV) (19.0µl±3.3 vs. 32.7µl±10.3; n=10; p=0.002) compared to non-transgenic controls. In contrast NG2-Cre x CXCL12flox/flox mice showed no significant changes in EF (34.6%±11.4 vs. 40.0%±8.1; n=10; p=0.368) and SV (27.7µl±7.3 vs. 32.7µl±10.3; n=10; p=0.303). Conclusion Our findings suggest that pericyte specific CXCL12 plays no major role in cardiac development and function after MI. In contrast, KO of CXCL12 in smooth muscle seems to deteriorate cardiac function after ischemia.

Echocardiography-based risk score predicts cardiovascular outcomes in ischemic heart failure patients with reduced ejection fraction

Abstract Background Ischemic heart disease (IHD) is the most common cause of heart failure (HF) and serves as an important prognostic factor across the whole HF spectrum. Prognostic assessment is important for optimal patient care, and a number of prediction models or prognostic scores have been developed in the past years for risk stratification of HF patients. Purpose Present study aimed to develop a comprehensive echocardiography-based score algorism for risk assessment of ischemic heart failure (IHF) patients with reduced left ventricular ejection fraction (&amp;lt;50%). Methods This study included 1355 IHF patients with ejection fraction &amp;lt;50%, the median clinical follow-up was 25 months. Multivariable Cox hazard models were used to assess the associations between echocardiography variables [including 13 standard parameters and global longitudinal strain (GLS)] and major adverse outcomes [including all-cause mortality, cardiovascular (CV) death, and CV related hospitalization]. Results Rates of all-cause mortality, CV mortality, and combined CV events including death and hospitalization, were 29.2%, 18.2%, 41.1%, respectively. Right ventricular mid-cavity diameter (RVD)&amp;gt;38mm, mitral annular plane systolic excursion (MAPSE)&amp;lt;8mm, tricuspid annular plane systolic excursion (TAPSE)&amp;lt;12mm, transmitral early flow velocity to mitral annular velocity ratio (E/E´)&amp;gt;14.5, systolic pulmonary artery pressure (sPAP)&amp;gt;38mmHg, and absolute GLS&amp;lt;8% were identified as independent echocardiographic indexes for worse clinical outcome in the multivariable Cox models. An echocardiography-based risk score (Echo Risk Score, ranged from 0 to 6 points) was established based on these markers and patients were classified into 3 risk groups: a score of 0 to 1 as low-risk, 2 to 3 as intermediate-risk, and 4-6 as high-risk. After adjustment for all clinical covariates, high-risk patients faced 2 to 3-fold increased risk of all-cause mortality (HR 2.42, 95% CI 1.81-3.24), CV mortality (HR 2.75, 95% CI 1.88-4.02), and combined CV events (HR 1.84, 95% CI 1.43-2.36) compared with low-risk patients. Incremental predicting efficacy was evidenced after the addition of Echo Risk Score either to the model including clinical risk factors or to the model including clinical risk factors and N-terminal prohormone of brain natriuretic peptide (all P&amp;lt;0.001, Figure 1). Conclusions This new echocardiography-based risk score is significantly and independently associated with all-cause mortality and CV mortality or hospitalization in ischemic heart failure patients with reduced ejection fraction. Future studies are warranted to validate the predicting efficacy of this echocardiography-based risk score in ischemic heart failure patients with reduced ejection fraction.Figure 1

Metabolome Profiling in the Plasma of Dogs with Idiopathic Dilated Cardiomyopathy: A Multiplatform Mass-Spectrometry-Based Approach.

Dilated cardiomyopathy is one of the important diseases in dogs and humans. The second most common cause of heart failure in dogs is idiopathic dilated cardiomyopathy (iDCM), which results in heart failure or sudden cardiac death due to arrhythmia. This study aimed to determine changes in the plasma metabolome of dogs with iDCM compared to healthy dogs. For that purpose, a multiplatform mass-spectrometry-based approach was used. In this study, we included two groups of dogs: 12 dogs with iDCM and 8 healthy dogs. A total of 272 metabolites were detected in the plasma samples of dogs by combining three approaches but four MS-based platforms (GC-MS, LC-MS (untargeted), LC-MS (targeted), and FIA-MS (targeted) methods). Our findings demonstrated changes in the canine plasma metabolome involved in the development of iDCM, including the different concentrations of amino acids, biogenic amines, acylcarnitines, triglycerides and diglycerides, sphingomyelins, and organic acids. The results of this study will enable the detection and monitoring of pathophysiological mechanisms involved in the development of iDCM in the future.

Transcriptional Activity of Metalloproteinase 9 (MMP-9) and Tissue Metalloproteinase 1 (TIMP-1) Genes as a Diagnostic and Prognostic Marker of Heart Failure Due to Ischemic Heart Disease.

The most common cause of heart failure (HF) is coronary artery disease (CAD). The aim of this study was to evaluate the transcriptional activity of the metalloproteinase 9 (MMP-9) and tissue metalloproteinase inhibitor 1 (TIMP-1) genes in a study group of patients with HF due to CAD and in the control group, as well as assess the transcriptional activity of the examined genes, taking into account the number of affected coronary arteries and the severity of heart failure. The study group consisted of a total of 150 (100%) patients. The material for the study was peripheral blood, and molecular tests were performed using the quantitative QRT-PCR technique. The transcriptional activity of the MMP-9 gene was significantly higher in the group of patients with CAD and HF. It was also significantly higher with the progression of heart failure. TIMP-1 gene transcriptional activity was significantly lower with the advancement of heart failure. The transcriptional activity of the MMP-9 and TIMP-1 genes differentiated the examined patients. The severity of HF, and a significant increase in the QRT-PCR transcriptional activity of the MMP-9 gene with a simultaneous decrease in the activity of the TIMP-1 gene, makes them useful diagnostic and prognostic markers in clinical practice.

Spectrum and prevalence of renal dysfunction among heart failure patients attending tertiary care hospital: first report from Somalia

IntroductionHeart failure is one of the major global health problems that we face today, worldwide. The main objective of our study is to evaluate the spectrum and prevalence of renal dysfunction among heart failure patients in Mogadishu, Somalia. The design of the study is a retrospective descriptive study aimed at heart failure patients who presented to the largest tertiary care center in southern somalia between January 2021 to september 2021. Demographic data, co-morbidities, types of heart failure, causes of heart failure and the presence or absence of renal dysfunction were analysed.ResultsOverall 180 heart failure patients were enrolled in the study. The mean age of the participants was 62.26 ± 14 years. Regarding the age group, patients aged between 61–80 years was the most abundant participants with (n = 87, 48.3%). Regarding the type of heart failure in our study, HFpEF was the most common type in our respondents with frequency of (n = 85, 47.2%). When analysed the cause of heart failure among patients; hypertension was the most common cause of heart failure (n = 90, 50%). Also, hypertension was the most common co-morbidity among our patients (n = 106, 59%), followed by coronary artery diseases (n = 50, 28%). The prevalence of renal dysfunction in heart failure patients was (n = 37, 20.6%). Our analysis showed that among the 37 renal dysfunction patients, 12.3% of them (n = 22) were CKD (chronic kidney disease) while the remaining 8.3% (n = 15) had AKI (acute kidney injury). We found a significant correlation between gender and renal dysfunction in heart failure patients with (95% CI: 0.098–0.574, OR: 0.237, p value: < 0.001). Males were 2 and half times more likely to develop renal failure than females.Conclusionswe found that the prevalence of renal dysfunction in heart failure patients is 20.6%. It was more prevalent in males and elderly population.

Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human

BackgroundDilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.MethodsWe performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.ResultsOur results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.ConclusionsCollectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.

Interim analysis of a prospective observational multicenter registry study of patients with chronic heart failure in the Russian Federation "PRIORITET-CHF": initial characteristics and treatment of the first included patients

Aim. To describe demographic and clinical laboratory characteristics, concomitant diseases and drug therapy of outpatients with heart failure (HF) in the Russian Federation.Material and methods. An interim analysis of a prospective observational multicenter registry study of patients with chronic heart failure in the Russian Federation ("PRIORITET-CHF") was performed. The study included outpatients with HF followed by a general practitioner or cardiologist.Results. Data from 6255 patients were analyzed (31,3% of the study sample; median age, 65 years; men, 65%). HF with reduced ejection fraction (HFrEF) was diagnosed in 42,4%, HF with preserved EF — in 31,9%. In addition, 57,4% of patients were characterized by NYHA class II HF. The most common causes of HF were hypertension, coronary artery disease, and atrial fibrillation or flutter. Of the concomitant diseases, doctors most often reported chronic kidney disease (CKD) (43,2%), obesity (37,8%) and diabetes (26,7%) in HF.Conclusion. In the Russian Federation, among outpatients with HF, there was domination of men, HFrEF phenotype, NYHA class II. The relatively young mean age and frequent associations of HF with cardiovascular risk factors and diseases underscore the importance of timely prevention initiatives. The identified high proportion of patients with CKD requires special attention and separate analysis. Despite the relatively high prescription rate of certain classes of diseasemodifying therapy for HF, the prescription of optimal quadruple therapy and electrophysiological treatments for HFrEF is insufficient.

Machine learning-based risk prediction model for canine myxomatous mitral valve disease using electronic health record data.

Myxomatous mitral valve disease (MMVD) is the most common cause of heart failure in dogs, and assessing the risk of heart failure in dogs with MMVD is often challenging. Machine learning applied to electronic health records (EHRs) is an effective tool for predicting prognosis in the medical field. This study aimed to develop machine learning-based heart failure risk prediction models for dogs with MMVD using a dataset of EHRs. A total of 143 dogs with MMVD between May 2018 and May 2022. Complete medical records were reviewed for all patients. Demographic data, radiographic measurements, echocardiographic values, and laboratory results were obtained from the clinical database. Four machine-learning algorithms (random forest, K-nearest neighbors, naïve Bayes, support vector machine) were used to develop risk prediction models. Model performance was represented by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). The best-performing model was chosen for the feature-ranking process. The random forest model showed superior performance to the other models (AUC = 0.88), while the performance of the K-nearest neighbors model showed the lowest performance (AUC = 0.69). The top three models showed excellent performance (AUC ≥ 0.8). According to the random forest algorithm's feature ranking, echocardiographic and radiographic variables had the highest predictive values for heart failure, followed by packed cell volume (PCV) and respiratory rates. Among the electrolyte variables, chloride had the highest predictive value for heart failure. These machine-learning models will enable clinicians to support decision-making in estimating the prognosis of patients with MMVD.

Role of serum cytokines in the prediction of heart failure in patients with coronary artery disease.

Coronary artery disease (CAD) is the most common cause of heart failure (HF). This study aimed to identify cytokine biomarkers for predicting HF in patients with CAD. Twelve patients with CAD without HF (CAD-non HF), 12 patients with CAD complicated with HF (CAD-HF), and 12 healthy controls were enrolled for Human Cytokine Antibody Array, which were used as the training dataset. Then, differentially expressed cytokines among the different groups were identified, and crucial characteristic proteins related to CAD-HF were screened using a combination of the least absolute shrinkage and selection operator, recursive feature elimination, and random forest methods. A support vector machine (SVM) diagnostic model was constructed based on crucial characteristic proteins, followed by receiver operating characteristic curve analysis. Finally, two validation datasets, GSE20681 and GSE59867, were downloaded to verify the diagnostic performance of the SVM model and expression of crucial proteins, as well as enzyme-linked immunosorbent assay was also used to verify the levels of crucial proteins in blood samples. In total, 12 differentially expressed proteins were overlapped in the three comparison groups, and then four optimal characteristic proteins were identified, including VEGFR2, FLRG, IL-23, and FGF-21. After that, the area under the receiver operating characteristic curve of the constructed SVM classification model for the training dataset was 0.944. The accuracy of the SVM classification model was validated using the GSE20681 and GSE59867 datasets, with area under the receiver operating characteristic curve values of 0.773 and 0.745, respectively. The expression trends of the four crucial proteins in the training dataset were consistent with those in the validation dataset and those determined by enzyme-linked immunosorbent assay. The combination of VEGFR2, FLRG, IL-23, and FGF-21 can be used as a candidate biomarker for the prediction and prevention of HF in patients with CAD.

Mesenchymal stromal cells for improvement of cardiac function following acute myocardial infarction: a matter of timing.

Acute myocardial infarction (AMI) is the leading cause of cardiovascular death and remains the most common cause of heart failure. Reopening of the occluded artery, i.e., reperfusion, is the only way to save the myocardium. However, the expected benefits of reducing infarct size are disappointing due to the reperfusion paradox, which also induces specific cell death. These ischemia-reperfusion (I/R) lesions can account for up to 50% of final infarct size, a major determinant for both mortality and the risk of heart failure (morbidity). In this review, we provide a detailed description of the cell death and inflammation mechanisms as features of I/R injury and cardioprotective strategies such as ischemic postconditioning as well as their underlying mechanisms. Due to their biological properties, the use of mesenchymal stromal/stem cells (MSCs) has been considered a potential therapeutic approach in AMI. Despite promising results and evidence of safety in preclinical studies using MSCs, the effects reported in clinical trials are not conclusive and even inconsistent. These discrepancies were attributed to many parameters such as donor age, in vitro culture, and storage time as well as injection time window after AMI, which alter MSC therapeutic properties. In the context of AMI, future directions will be to generate MSCs with enhanced properties to limit cell death in myocardial tissue and thereby reduce infarct size and improve the healing phase to increase postinfarct myocardial performance.

Ischemic Etiology in Advanced Heart Failure: Insight from the HELP-HF Registry

In patients with advanced heart failure (HF), defined according to the presence of at least one I-NEED-HELP criterium, the updated 2018 Heart Failure Association of the European Society of Cardiology (HFA-ESC) criteria for advanced HF identify a subgroup of patients with HF with worse prognosis, but whether ischemic etiology has a relevant prognostic impact in this very high-risk cohort is unknown. Patients from the HELP-HF registry were stratified according to ischemic etiology and presence of advanced HF based on 2018 HFA-ESC criteria. The primary end point was a composite of all-cause death and HF hospitalization at 1year. Secondary end points were all-cause death, HF hospitalization, and cardiovascular death at 1year. Ischemic etiology was a leading cause of HF, in both patients with advanced and nonadvanced HF (46.1% and 42.4%, respectively, p=0.337). The risk of the primary end point (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.58) and all-cause mortality (HR 1.37, 95% CI 1.06 to 1.76) was increased in ischemic as compared with nonischemic patients. The risk of the primary end point was consistently higher in ischemic patients in both patients with advanced and nonadvanced HF (advanced HF, HR 1.50 95% CI 1.04 to 2.16; nonadvanced HF, HR 1.25 95% CI 1.01 to 1.56, pinteraction=0.333), driven by an increased risk of mortality, mainly because of cardiovascular causes. In conclusion, ischemic etiology is the most common cause of HF in patients with at least one I-NEED-HELP marker and with or without advanced HF as defined by the 2018 HFA-ESC definition. In both patients with advanced and not-advanced HF, ischemic etiology carried an increased risk of worse prognosis.

Abstract EC.04: The Effects Of Cardiac Troponin Activator CK-358 On Cardiac Contractility In A Mouse Model Of Genetic Dilated Cardiomyopathy

Genetic dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. However, most treatments do not address the underlying contractile deficit caused by the disease. In an effort to create more targeted DCM therapeutics, novel small molecule drugs known as sarcomeric modulators have been of recent interest. In a recent study, a cardiac troponin activator was shown to improve cardiac muscle contractility without adversely affecting energetics or diastolic function. Here, we aim to elucidate the mechanism by which the cardiac troponin activator CK-3827358 (CK-358) is able to recover contractile function in a mouse model of DCM with a mutation at residue 61 of cardiac troponin C (cTnC I61Q). We measured steady state force and k tr , a measure of crossbridge cycling kinetics, in demembranated ventricular tissue from control and cTnC I61Q mice in solutions with increasing concentrations of calcium, ranging from pCa 9 to pCa 4. The cTnC I61Q mutation significantly decreased calcium sensitivity versus control (pCa 50 : 5.48 ± 0.06 vs 5.75 ± 0.01). Compared to controls, CK-358 (1 μM) significantly increased calcium sensitivity (pCa 50 ) in tissue from both cTnC I61Q and control mice (6.03 ± 0.06 and 6.50 ± 0.18, P=0.005) without any change in maximum force. CK-358 also significantly increased k tr , possibly suggesting activation of thin filaments. Next, we used a fluorescently labeled human cardiac troponin C (HcTnC) conjugated to N,N′-dimethyl-N-(iodoacetyl)-N′-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)ethylenediamine (IANBD) combined with subunits T and I to make a full HcTn complex. We performed calcium titrations with the HcTn-IANBD and saw no change in fluorescence in the control protein with and without CK-358. Finally, we performed HcTnC titrations with HcTnI and saw no change in fluorescence at maximum, sub-maximum, and minimum calcium concentrations. Overall, we demonstrate that cardiac troponin activator CK-358 did not alter calcium binding to HcTnC or its interaction with HcTnI. However, it restores the calcium sensitivity of cTnC I61Q DCM ventricular sarcomeres. Future studies will examine the effects of CK-358 on calcium binding in decorated thin filaments and measure activation using stopped flow spectroscopy in this model of DCM.