Higher Risk Of Heart Failure Research Articles

Weight telemonitoring of heart failure versus standard of care in a real-world setting: Results on mortality and hospitalizations in a 6-month nationwide matched cohort study.

Evaluating the benefit of telemonitoring in heart failure (HF) management in real-world settings is crucial for optimizing the healthcare pathway. The aim of this study was to assess the association between a 6-month application of the telemonitoring solution Chronic Care Connect™ (CCC) and mortality, HF hospitalizations, and associated costs compared with standard of care (SOC) in patients with a diagnosis of HF. From February 2018 to March 2020, a retrospective cohort study was conducted using the largest healthcare insurance system claims database in France (Système National des Données de Santé) linked to the CCC telemonitoring database of adult patients with an ICD-10-coded diagnosis of HF. Patients from the telemonitoring group were matched with up to two patients from the SOC group based on their high-dimensional propensity score, without replacement, using the nearest-neighbour method. A total of 1358 telemonitored patients were matched to 2456 SOC patients. The cohorts consisted of high-risk patients with median times from last HF hospitalization to index date of 17.0 (interquartile range: 7.0-66.0) days for the telemonitoring group and 27.0 (15.0-70.0) days for the SOC group. After 6 months, telemonitoring was associated with mortality risk reduction (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.56-0.89), a higher risk of first HF hospitalization (HR 1.81, 95% CI 1.55-2.13), and higher HF healthcare costs (relative cost 1.38, 95% CI 1.26-1.51). Compared with the SOC group, the telemonitoring group experienced a shorter average length of overnight HF hospitalization and fewer emergency visits preceding HF hospitalizations. The results of this nationwide cohort study highlight a valuable role for telemonitoring solutions such as CCC in the management of high-risk HF patients. However, for telemonitoring solutions based on weight and symptoms, consideration should be given to implement additional methods of assessment to recognize imminent worsening of HF, such as impedance changes, as a way to reduce mortality risk and the need for HF hospitalizations. Further studies are warranted to refine selection of patients who could benefit from a telemonitoring system and to confirm long-term benefits in high-risk and stable HF patients.

Association of inflammatory markers with incident heart failure or cancer in the HUNT3 and Health ABC population studies.

To investigate the relationship between chronic low-grade inflammation, as measured by high-sensitivity C-reactive protein (hsCRP) levels, and incident heart failure (HF) or cancer. We assessed the relationship between baseline hsCRP concentrations and subsequent HF or cancer in two community-based cohorts, the Trøndelag Health Study (HUNT3) and the Health, Aging and Body Composition (ABC) study. In the latter, the analysis was replicated with interleukin (IL)-1, IL-6, or tumour necrosis factor (TNF)-α instead of hsCRP. In HUNT3, hsCRP was measured in 47 163 subjects (mean age 52.3 ± 15.8 years). During a median follow-up of 12.1 years, 2034 (4.3%) individuals developed HF and 5024 (10.7%) cancer, with 442 (0.9%) being diagnosed with both. After adjusting for age, male sex, diabetes, obesity, previous or current smoking, and comorbidities, elevated baseline hsCRP was associated with a higher risk of HF or cancer [hazard ratio (HR) 1.09; 95% confidence interval (CI), 1.07-1.10]. In the Health ABC study, hsCRP levels were assessed in 2803 participants, who had a mean age of 72.6 ± 2.9 years and a higher burden of comorbidities than in HUNT3. During a median follow-up of 8.2 years, HF and cancer were diagnosed in 346 (12.3%) and 776 (27.7%) subjects, respectively, with 77 (2.7%) having both conditions. After adjusting for the same variables used for the HUNT3 cohort, hsCRP remained significantly associated with incident HF or cancer (HR 1.11; 95% CI, 1.05-1.18), as were IL-1 (HR 1.15; 1.07-1.24), IL-6 (HR 1.09; 1.02-1.17), and TNF-α (HR 1.15; 1.07-1.24). A state of chronic, low-grade inflammation captured by an increase in hsCRP levels is associated with an increased risk of developing HF or cancer, with potential implications for clinical trials with anti-inflammatory therapies.

Ready-to-Eat Food Environments and Risk of Incident Heart Failure: A Prospective Cohort Study.

Food environments have been linked to cardiovascular diseases; however, few studies have assessed the relationship between food environments and the risk of heart failure (HF). We aimed to evaluate the association between ready-to-eat food environments and incident HF at an individual level in a large prospective cohort. Exposure to ready-to-eat food environments, comprising pubs or bars, restaurants or cafeterias, and fast-food outlets, were individually measured as both proximity and density metrics. We also developed a composite ready-to-eat food environment density score by summing the densities of 3 types of food environments. Cox proportional analyses were applied to assess the associations of each single type and the composite food environments with HF risk. Closer proximity to and greater density of ready-to-eat food environments, particularly for pubs and bars and fast-food outlets (P<0.05 for both proximity and density metric) were associated with an elevated risk of incident HF. Compared with those with no exposure to composite ready-to-eat food environments, participants in the highest density score category had a 16% (8%-25%; P<0.0001) higher risk of HF. In addition, we found significant interactions of food environments with education, urbanicity, and density of physical activity facilities on HF risk (all Pinteraction<0.05); the ready-to-eat food environments-associated risk of HF was stronger among participants who were poorly educated, living in urban areas, and without physical activity facilities. Exposure to ready-to-eat food environments is associated with a higher risk of incident HF, suggesting the potential importance of minimizing unfavorable food environments in the prevention of HF.

Daprodustat and Heart Failure in CKD.

Patients with chronic kidney disease (CKD) are at higher risk for heart failure. The hypoxia inducible factor prolyl hydroxylase inhibitor daprodustat is an orally acting alternative to conventional injectable erythropoietin-stimulating agents (ESA) for the treatment of anemia in patients with CKD. Whether daprodustat affects the risk of heart failure hospitalization is unknown. The ASCEND-D (n=2,964) and ASCEND-ND (n=3,872) trials compared daprodustat to conventional ESA in patients with anemia of CKD who did or did not require dialysis, respectively. We identified risk factors for heart failure hospitalization and assessed the effect of daprodustat compared to conventional ESA on heart failure hospitalizations. History of heart failure, diabetes, and higher systolic blood pressure were independently associated with heart failure hospitalization in both trials, irrespective of treatment assignment. The number of first heart failure hospitalizations was greater in the daprodustat arm in patients not receiving dialysis (hazard ratio [HR] 1.22 [0.95-1.56], p=0.12] and in patients receiving dialysis (HR 1.10 [0.84-1.45], p=0.47), though these differences were not statistically significant. HRs in patients with and without history of heart failure were 1.37 (0.89-2.11) vs 1.08 (0.79-1.46) (p-interaction=0.36) in ASCEND-ND, and 1.52 (0.97-2.38) vs 0.93 (0.66-1.30) (p-interaction=0.09) in ASCEND-D, respectively. In post hoc analyses, daprodustat increased total (first and recurrent) heart failure hospitalizations in participants not receiving dialysis (rate ratio 1.46 [1.11-1.92], p=0.007) ) but not in participants receiving dialysis (rate ratio 1.01 [0.74-1.39], p=0.93). Daprodustat did not significantly affect the risk of a composite outcome of first heart failure hospitalization or death. A greater number of first heart failure hospitalization events occurred in patients treated with daprodustat compared with conventional ESA, but this difference did not reach statistical significance. Differences in the number of heart failure hospitalization events were most apparent in patients not receiving dialysis and in patients with history of heart failure.

Genetic Characterization of Dilated Cardiomyopathy in Romanian Adult Patients.

Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of <35% was observed in 41.9% of patients with disease-causing variants and 55% with negative or uncertain findings. Further genotype-phenotype correlations were explored in this study population. The substantial percentage (50.8%) of disease-causing variants identified in patients with DCM acknowledges the importance of genetic investigations. This study highlights the genetic landscape in genes associated with DCM in the Romanian population.

Self-Reported Outdoor Light Exposure Time and Incident Heart Failure.

A healthy lifestyle is an important factor for preventing heart failure. However, the association between outdoor light exposure time and heart failure is still unknown. The aim of this study was to examine the association between outdoor light exposure time and the incidence of heart failure. This cohort study included participants from the UK Biobank recruited from 2006 to 2010 who were 40 to 70 years of age and free of heart failure at baseline. The mean follow-up time was 12.61 years. The outdoor light exposure time was self-reported at baseline. A restricted cubic spline was performed to examine the potential nonlinear relationship between outdoor light exposure and the incidence of heart failure. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% CIs. During a mean follow-up of 12.61 years, 13 789 participants were first diagnosed with heart failure. There was a nonlinear (J-shaped) trend between outdoor light time and heart failure risk. Cox proportional hazard regression models showed that, compared with participants who received an average of 1.0 to 2.5 hours of outdoor light per day, those with <1.0 hours or >2.5 hours had a higher risk of heart failure after the model was adjusted for age and sex (<1.0 hours: HR, 1.27 [95% CI, 1.18-1.36]; >2.5 hours: HR, 1.11 [95% CI, 1.07-1.15]). These associations were still significant in the fully adjusted models (<1.0 hours: HR, 1.10 [95% CI, 1.03-1.18]; >2.5 hours: HR, 1.07 [95% CI, 1.03-1.11]). We found a J-shaped association between outdoor light exposure time and the risk of incident heart failure, suggesting that moderate exposure to outdoor light may be a prevention strategy for heart failure.

Sex and Age Differences in the Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and Heart Failure: A Prospective Cohort Study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a risk factor for heart failure (HF) occurrence, but it remains unclear whether the association between MAFLD and HF differs in different sexes and ages. A total of 96 576 participants of Kailuan Study were included. MAFLD was defined as presence of hepatic steatosis and metabolic dysfunction and classified as mild and significant by ultrasound. Hazard ratios (HRs) were calculated by Cox regression models. After a median follow-up of 14.0 years, 2939 participants developed HF. Adjusting for confounding factors, mild-MAFLD (HR, 1.27 [95% CI, 1.16-1.39]) and significant-MAFLD (HR, 1.45 [95% CI, 1.31-1.63]) were associated with a higher risk of HF in all participants, and the risk differed by sex (Pinteraction<0.05) and age (Pinteraction<0.001). Compared with non-MAFLD participants, in women, significant-MAFLD was associated with an 84% (HR, 1.84 [95% CI, 1.43-2.37]) increased risk of HF; however, in men, the risk was 36% (HR, 1.36 [95% CI, 1.20-1.53]). In participants under 45 years, mild-MAFLD and significant-MAFLD had a 55% (HR, 1.55 [95% CI, 1.07-2.25]) and 172% (HR, 2.72 [95% CI, 1.87-3.97]) increased risk of HF; however, in participants over 65 years, even significant-MAFLD did not associate with a higher risk of HF (HR, 1.11 [95% CI, 0.92-1.34]). Afterwards, we stratified all participants by both sex and age and found that the risk of MAFLD-associated HF decreased with age in men (Pinteraction<0.05) and women (Pinteraction<0.05), but the sex difference in this risk was only present in participants younger than 45 years (Pinteraction<0.05). MAFLD greatly increased the risk of HF in women, especially young women. With increasing age, MAFLD-related risk of HF decreased and the difference between men and women disappeared.

Radiomics from Cardiovascular MR Cine Images for Identifying Patients with Hypertrophic Cardiomyopathy at High Risk for Heart Failure.

Purpose To develop a model integrating radiomics features from cardiac MR cine images with clinical and standard cardiac MRI predictors to identify patients with hypertrophic cardiomyopathy (HCM) at high risk for heart failure (HF). Materials and Methods In this retrospective study, 516 patients with HCM (median age, 51 years [IQR: 40-62]; 367 [71.1%] men) who underwent cardiac MRI from January 2015 to June 2021 were divided into training and validation sets (7:3 ratio). Radiomics features were extracted from cardiac cine images, and radiomics scores were calculated based on reproducible features using the least absolute shrinkage and selection operator Cox regression. Radiomics scores and clinical and standard cardiac MRI predictors that were significantly associated with HF events in univariable Cox regression analysis were incorporated into a multivariable analysis to construct a combined prediction model. Model performance was validated using time-dependent area under the receiver operating characteristic curve (AUC), and the optimal cutoff value of the combined model was determined for patient risk stratification. Results The radiomics score was the strongest predictor for HF events in both univariable (hazard ratio, 10.37; P < .001) and multivariable (hazard ratio, 10.25; P < .001) analyses. The combined model yielded the highest 1- and 3-year AUCs of 0.81 and 0.80, respectively, in the training set and 0.82 and 0.77 in the validation set. Patients stratified as high risk had more than sixfold increased risk of HF events compared with patients at low risk. Conclusion The combined model with radiomics features and clinical and standard cardiac MRI parameters accurately identified patients with HCM at high risk for HF. Keywords: Cardiomyopathies, Outcomes Analysis, Cardiovascular MRI, Hypertrophic Cardiomyopathy, Radiomics, Heart Failure Supplemental material is available for this article. © RSNA, 2024.

Predicting heart failure outcomes by integrating breath-by-breath measurements from cardiopulmonary exercise testing and clinical data through a deep learning survival neural network.

Mathematical models previously developed to predict outcomes in patients with heart failure (HF) generally have limited performance and have yet to integrate complex data derived from cardiopulmonary exercise testing (CPET), including breath-by-breath data. We aimed to develop and validate a time-to-event prediction model using a deep learning framework using the DeepSurv algorithm to predict outcomes of HF. Inception cohort of 2490 adult patients with high-risk cardiac conditions or HF underwent CPET with breath-by-breath measurements. Potential predictive features included known clinical indicators, standard summary statistics from CPETs, and mathematical features extracted from the breath-by-breath time series of 13 measurements. The primary outcome was a composite of death, heart transplant, or mechanical circulatory support treated as a time-to-event outcomes. Predictive features ranked as most important included many of the features engineered from the breath-by-breath data in addition to traditional clinical risk factors. The prediction model showed excellent performance in predicting the composite outcome with an area under the curve of 0.93 in the training and 0.87 in the validation data sets. Both the predicted vs. actual freedom from the composite outcome and the calibration of the prediction model were excellent. Model performance remained stable in multiple subgroups of patients. Using a combined deep learning and survival algorithm, integrating breath-by-breath data from CPETs resulted in improved predictive accuracy for long-term (up to 10 years) outcomes in HF. DeepSurv opens the door for future prediction models that are both highly performing and can more fully use the large and complex quantity of data generated during the care of patients with HF.

Abnormal circulating steroids refine risk of progression to heart failure in ischemic heart disease.

Patients with ischemic heart disease (IHD) experience a high incidence of progression to heart failure (HF) despite current therapies. We speculated that steroid hormone metabolic disorders distinct adverse phenotypes and contribute to HF. We measured 18 steroids using liquid chromatography with tandem mass spectrometry in 2023 patients from the Registry Study of Biomarkers in Ischemic Heart Disease (BIOMS-IHD), including 1091 patients with IHD in a retrospective discovery set and 932 patients with IHD in a multicentre validation set. Our outcomes included incident HF after a median follow-up of 4 years. We demonstrated steroid-based signatures of inflammation, coronary microvascular dysfunction and left ventricular hypertrophy that were associated with subsequent HF events in patients with IHD. In both cohorts, patients with a high steroid-heart failure score (SHFS) (>1) exhibited a greater risk of incident HF than patients with a low SHFS (≤1). The SHFS further improved the prognostic accuracy beyond clinical variables (net reclassification improvement of 0.628 in the discovery set and 0.299 in the validation set) and demonstrated the maximal effect of steroid signatures in patients with IHD who had lower B-type natriuretic peptide levels (pinteraction = 0.038). A steroid-based strategy can simply and effectively identify individuals at higher HF risk who may derive benefit from more intensive follow-ups.

Smoking Behavior Change and the Risk of Heart Failure in Patients With Type 2 Diabetes: Nationwide Retrospective Cohort Study.

Heart failure (HF) is one of the most common initial manifestations of cardiovascular disease in patients with type 2 diabetes. Although smoking is an independent risk factor for HF, there is a lack of data for the incidence of HF according to changes in smoking behaviors in patients with type 2 diabetes. We aimed to examine the association between interval changes in smoking behavior and the risk of HF among patients with type 2 diabetes. We conducted a retrospective cohort study using the National Health Insurance Service database. We identified 365,352 current smokers with type 2 diabetes who had 2 consecutive health screenings (2009-2012) and followed them until December 31, 2018, for the incident HF. Based on smoking behavior changes between 2 consecutive health screenings, participants were categorized into quitter, reducer I (≥50% reduction) and II (<50% reduction), sustainer (reference group), and increaser groups. During a median follow-up of 5.1 (IQR 4.0-6.1) years, there were 13,879 HF cases (7.8 per 1000 person-years). Compared to sustainers, smoking cessation was associated with lower risks of HF (adjusted hazard ratio [aHR] 0.90, 95% CI0.86-0.95), whereas increasers showed higher risks of HF than sustainers; heavy smokers who increased their level of smoking had a higher risk of HF (aHR 1.13, 95% CI 1.04-1.24). In the case of reducers, the risk of HF was not reduced but rather increased slightly (reducer I: aHR 1.14, 95% CI 1.08-1.21; reducer II: aHR 1.03, 95% CI 0.98-1.09). Consistent results were noted for subgroup analyses including type 2 diabetes severity, age, and sex. Smoking cessation was associated with a lower risk of HF among patients with type 2 diabetes, while increasing smoking amount was associated with a higher risk for HF than in those sustaining their smoking amount. There was no benefit from reduction in smoking amount.

Cardiovascular disease, depressive symptoms, and heart failure in Mexican American aged 75 years and older during 12 years of follow up

ObjectiveTo examine the relationship of cardiovascular disease (CVD) and high depressive symptoms (HDS) with heart failure (HF) among Mexican American older adults without HF at baseline over 12-years of follow-up. MethodsA 12-year prospective cohort study of 1,018 Mexicans Americans aged 75 and older from the Hispanic Established Population for the Epidemiologic Study of the Elderly (2004–2016). Measures included socio-demographics, CVD (heart attack or stroke), HDS, smoking status, body mass index, cognitive function, and HF. Participants were grouped into: CVD and HDS (n = 11), CVD only (n = 122), HDS only (n = 44), and no CVD or HDS (n = 841). Odds ratio (OR) and 95 % Confidence Interval (CI) of HF over time were estimated using the Generalized Estimating Equation. ResultsParticipants with CVD and HDS and those with HDS only had greater odds (OR=4.70, 95 %CI=1.98–11.2 and OR=3.26, 95 %CI=1.82–5.84, respectively) of HF over time, after controlling for all covariates. No significant association was found between CVD only and HF (OR=1.25, 95 %CI=0.90–1.76). ConclusionMexican American older adults with HDS only or both HDS and CVD were at high risk of HF. Appropriate management of CVD and depressive symptoms may reduce the onset of HF among this population.

Effect of carvedilol versus placebo on cardiac function in anthracycline-exposed survivors of childhood cancer (PREVENT-HF): a randomised, controlled, phase 2b trial

Carvedilol improves cardiac function in patients with heart failure but remains untested as cardioprotective therapy in long-term childhood cancer survivors (ie, those who have completed treatment for childhood cancer and are in remission) at risk for heart failure due to high-dose anthracycline exposure. We aimed to evaluate the activity and safety of low-dose carvedilol for heart failure risk reduction in childhood cancer survivors at highest risk for heart failure. PREVENT-HF was a randomised, double-blind, phase 2b trial done at 30 hospitals in the USA and Canada. Patients were eligible if they had any cancer diagnosis that resulted in at least 250 mg/m2 cumulative exposure to anthracycline by age 21 years; completed their cancer treatment at least 2 years previously; an ejection fraction of at least 50% or fractional shortening of at least 25%, or both; and bodyweight of at least 40 kg. Patients were randomly assigned (1:1) with automated computer-generated permuted block randomisation (block size of 4), stratified by age at diagnosis, time since diagnosis, and history of chest-directed radiotherapy, to carvedilol (up-titrated from 3·125 g per day to 12·5 mg per day) or placebo orally for 2 years. Participants, staff, and investigators were masked to study group allocation. The primary endpoint was to establish the effect of carvedilol on standardised left ventricular wall thickness-dimension ratio Z score (LVWT/Dz). Treatment effects were analysed with a linear mixed-effects model for normally distributed data with a linear time effect and testing the significance of treatment*time interaction in the modified intention-to-treat (mITT) cohort (ie, all randomly assigned participants who had a baseline and at least one subsequent echocardiogram measurement). Safety was assessed in the ITT population (ie, all randomly assigned participants). This trial was registered with ClinicalTrials.gov, NCT027175073, and enrolment and follow-up are complete. Between July 3, 2012, and June 22, 2020, 196 participants were enrolled, of whom 182 (93%) were eligible and randomly assigned to either carvedilol (n=89) or placebo (n=93; ITT population). Median age was 24·7 years (IQR 19·6-36·6), 91 (50%) participants were female, 91 (50%) were male, and 119 (65%) were non-Hispanic White. As of data cutoff (June 10, 2022), median follow-up was 725 days (IQR 378-730). 151 (n=75 in the carvedilol group and n=76 in the placebo group) of 182 participants were included in the mITT population, among whom LVWT/Dz was similar between the two groups (-0·14 [95% CI -0·43 to 0·16] in the carvedilol group vs -0·45 [-0·77 to -0·13] in the placebo group; difference 0·31 [95% CI -0·10 to 0·73]; p=0·14). Two (2%) of 89 patients in the carvedilol group two adverse events of grade 2 or higher (n=1 shortness of breath and n=1 arthralgia) and none in the placebo group. There were no adverse events of grade 3 or higher and no deaths. Low-dose carvedilol appears to be safe in long-term childhood cancer survivors at risk for heart failure, but did not result in significant improvement of LVWT/Dz compared with placebo. These results do not support the use of carvedilol for secondary heart failure prevention in anthracycline-exposed childhood cancer survivors. National Cancer Institute, Leukemia & Lymphoma Society, St Baldrick's Foundation, Altschul Foundation, Rally Foundation, American Lebanese Syrian Associated Charities.

Molecular Pathways and Animal Models of Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with underdevelopment of left-sided heart structures. While previously uniformly fatal, surgical advances now provide highly effective palliation that allows most HLHS patients to survive their critical CHD. Nevertheless, there remains high morbidity and mortality with high risk of heart failure. As hemodynamic compromise from restricted aortic blood flow has been suggested to underlie the poor LV growth, this suggests the possibility of prenatal fetal intervention to recover LV growth. As such interventions have yielded ambiguous results, the optimization of therapy will require more mechanistic insights into the developmental etiology for HLHS. Clinical studies have shown high heritability for HLHS, with an oligogenic etiology indicated in conjunction with genetic heterogeneity. This is corroborated with the recent recovery of mutant mice with HLHS. With availability-induced pluripotent stem cell (iPSC)-derived cardiomyocytes from HLHS mice and patients, new insights have emerged into the cellular and molecular etiology for the LV hypoplasia in HLHS. Cell proliferation defects were observed in conjunction with metaphase arrest and the disturbance of Hippo-YAP signaling. The left-sided restriction of the ventricular hypoplasia may result from epigenetic perturbation of pathways regulating left-right patterning. These findings suggest new avenues for fetal interventions with therapies using existing drugs that target the Hippo-YAP pathway and/or modulate epigenetic regulation.

Identification of miR-1 and miR-499 in chronic atrial fibrillation by bioinformatics analysis and experimental validation.

Atrial fibrillation (AF) is one of the most prevalent arrhythmias and is characterized by a high risk of heart failure and embolic stroke, yet its underlying mechanism is unclear. The primary goal of this study was to establish a miRNA-mRNA network and identify the miRNAs associated with chronic AF by bioinformatics and experimental validation. The GSE79768 dataset was collected from the Gene Expression Omnibus(GEO) database to extract data from patients with or without persistent AF. Differentially expressed genes (DEGs) were identified in left atrial appendages (LAAs). The STRING platform was utilized for protein-protein interaction (PPI) network analysis. The target miRNAs for the top 20 hub genes were predicted by using the miRTarBase Web tool. The miRNA-mRNA network was established and visualized using Cytoscape software. The key miRNAs selected for verification in the animal experiment were confirmed by miRwalk Web tool. We used a classic animal model of rapid ventricular pacing for chronic AF. Two groups of animals were included in the experiment, namely, the ventricular pacing group (VP group), where ventricular pacing was maintained at 240-280 bpm for 2 weeks, and the control group was the sham-operated group (SO group). Finally, we performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to validate the expression of miR-1 and miR-499 in LAA tissues of the VP group and the SO group. Left atrial fibrosis and apoptosis were evaluated by Masson staining and caspase-3 activity assays, respectively. The networks showed 48 miRNAs in LAA tissues. MiR-1 and miR-499 were validated using an animal model of chronic AF. The expression level of miR-1 was increased, and miR-499 was decreased in VP group tissues compared to SO group tissues in LAAs (P < 0.05), which were correlated with left atrial fibrosis and apoptosis in AF. This study provides a better understanding of the alterations in miRNA-1 and miR-499 in chronic AF from the perspective of the miRNA-mRNA network and corroborates findings through experimental validation. These findings may offer novel potential therapeutic targets for AF in the future.

Habitual Daily Intake of Fried Foods Raises Transgenerational Inheritance Risk of Heart Failure Through NOTCH1-Triggered Apoptosis.

Consumption of fried foods is highly prevalent in the Western dietary pattern. Western diet has been unfavorably linked with high risk of developing cardiovascular diseases. Heart failure (HF) as a cardiovascular disease subtype is a growing global pandemic with high morbidity and mortality. However, the causal relationship between long-term fried food consumption and incident HF remains unclear. Our population-based study revealed that frequent fried food consumption is strongly associated with 15% higher risk of HF. The causal relationship may be ascribed to the dietary acrylamide exposure in fried foods. Further cross-sectional study evidenced that acrylamide exposure is associated with an increased risk of HF. Furthermore, we discover and demonstrate that chronic acrylamide exposure may induce HF in zebrafish and mice. Mechanistically, we reveal that acrylamide induces energy metabolism disturbance in heart due to the mitochondria dysfunction and metabolic remodeling. Moreover, acrylamide exposure induces myocardial apoptosis via inhibiting NOTCH1-phosphatidylinositol 3-kinase/AKT signaling. In addition, acrylamide exposure could affect heart development during early life stage, and the adverse effect of acrylamide exposure is a threat for next generation via epigenetic change evoked by DNA methyltransferase 1 (DNMT1). In this study, we reveal the adverse effects and underlying mechanism of fried foods and acrylamide as a typical food processing contaminant on HF from population-based observations to experimental validation. Collectively, these results both epidemiologically and mechanistically provide strong evidence to unravel the mechanism of acrylamide-triggered HF and highlight the significance of reducing fried food consumption for lower the risk of HF.

Age and sex-related differences in epidemiology, treatment, and mortality of patients with ST-segment elevation myocardial infarction in Iran.

Few studies have investigated the characteristics of patients with ST elevation myocardial infarction (STEMI) according to age and sex in Iran. This study aims to investigate the risk factors profile, treatment, and mortality of STEMI based on age and sex. From 10th June 2016 to December 2019 a total of 2816, STEMI patients referred to the Imam Ali heart center of Kermanshah were included in the study. Profile of the risk factors, epidemiology, treatment and 30- day mortality for all cases in the age categories of 18-49, 50-64, and≥65 years were studied. There were 1256 (44.6%) middle-aged STEMI patients, and 2181 (77.45%) were male. The elderly had a longer median door-to-balloon and symptom-to-balloon time and received less primary PCI. In the absence of primary PCI, the rate of 30-day mortality in women was higher than in men, and the mortality rate increased with age. The risk of death in middle-aged women was higher than that of men. Also, in the middle-aged group, after multivariable adjustment, previous bypass surgery, diabetes, and Killip class≥2 was associated with significant increase in the risk of death. The present study showed that young people with STEMI had a high risk of heart failure and anterior infarction compared to the older age groups. Women had more risk factors for STEMI and a higher mortality rate than men. Therefore, there is a need to educate young age groups and women to modify their lifestyles and intervene in the risk factors of heart diseases.

Impact on clinical outcomes of renin-angiotensin system inhibitors against doxorubicin-related toxicity in patients with breast cancer and hypertension: A nationwide cohort study in South Korea.

Although doxorubicin (DOX) is a commonly used potent chemotherapeutic agent in patients with breast cancer, its cardiotoxic effect is a concern, particularly in patients with hypertension. Antihypertensive renin-angiotensin system (RAS) inhibitors may potentially play a role in preventing overt heart failure (HF) due to DOX toxicity. This study aimed to evaluate whether the use of RAS inhibitors improves clinical outcomes in patients with hypertension and breast cancer undergoing DOX-containing chemotherapy. A total of 54,344 female patients who were first diagnosed with breast cancer and initiated into DOX therapy between 2008 and 2015 were recruited from a nationwide Korean cohort. Patients were divided into two groups: with and without hypertension (HT, n = 10,789; non-HT, n = 43,555), and the RAS inhibitor group (n = 1,728) was sub-classified from the HT group. Two propensity score-matched cohorts were constructed to compare the clinical outcomes between non-HT and HT groups and between non-HT and RAS inhibitor groups. The primary outcome was the composite of HF and death. After propensity score matching, the HT group had a higher risk for HF (adjusted hazard ratio [HR] = 1.30, 95% confidence intervals [95% CI] = 1.09-1.55) compared to the non-HT group, but there was no significant difference in primary outcome between the two groups. The RAS inhibitor group had a lower risk for primary outcome (adjusted HR = 0.78, 95% CI = 0.65-0.94) and death (adjusted HR = 0.81, 95% CI = 0.66-0.99) compared to the non-HT group. Hypertension is a risk factor for HF in patients with breast cancer undergoing DOX chemotherapy. However, the RAS inhibitors used to treat hypertension may contribute to decreased mortality and improved clinical outcomes.

A Real-World Analysis of New-Onset Heart Failure After Anterior Wall ST-Elevation Acute Myocardial Infarction in the United States

The 1-year incidence of heart failure (HF) after anterior wall ST-elevation acute myocardial infarction (STEMI) remains difficult to determine because of inconsistencies in reporting, definitions, and adjudication. The objective of this study was to evaluate the 1-year incidence of HF after anterior wall STEMI in a real-world data set using a variety of potential criteria and composite definitions. In a retrospective cohort study, anonymized patient data was accessed through a federated health research network (TriNetX Limited Liability Company (LLC)) of 56 US healthcare organizations (US Collaborative Network). Patients were identified based on the International Classification of Diseases, Tenth Revision criteria for anterior wall STEMI during the 10-year period from 2013 to 2022 and the absence of prespecified signs or symptoms of HF. Values for 1-year incidence were calculated as 1 minus Kaplan-Meier survival at 12months after anterior wall STEMI. Univariate Cox proportional hazard ratio was calculated to compare risk associated with potential risk factors. The analysis utilized 5 different types of definition criteria for HF: Diagnosis codes, Signs and symptoms, Laboratory/imaging, Medications, and Composites. A total of 34,395 patients from the US Collaborative Network met eligibility criteria and were included in the analysis. The 1-year incidence of HF varied from 2% to 30% depending upon the definition criteria. Although no single criteria exceeded a 1-year incidence of 20%, a simple composite of HF diagnosis (International Classification of Diseases, Tenth Revision-I50) or use of loop diuretic produced a 1-year incidence 26.1% that was used as the benchmark outcome for evaluation of risk factors. Age ≥65years, Black race, low-density lipoprotein ≥100mg/100ml, elevated hemoglobin A1c (7% to 9% and >9%), and body mass index≥35kg/m2 were also associated with increased risk of HF. In conclusion, patients with anterior wall STEMI continue to be at high risk for new-onset HF. In the absence of structured, prospective, systematically adjudicated diagnostic criteria, composite definitions are more likely to yield accurate estimates of HF incidence.

Impact of patient characteristics on heart failure and cardiomyopathy onset related to pregnancy from 1997 to 2019. Swedish nationwide register-based study

Abstract Background The aetiology of heart failure (HF) in young patients is heterogenic. Cardiomyopathies are common causes in young patients, that often unmask in situations of higher physical demands, as pregnancy or delivery, presenting with HF signs and symptoms. Peripartum cardiomyopathy (PPCM) is one form associated with delivery. However, even other, such as dilated or hypertrophic cardiomyopathy may present during pregnancy. Despite major advances in care, there is still a lack of knowledge about factors that trigger heart failure onset during pregnancy and delivery. Aim To evaluate the association of baseline characteristics for HF and cardiomyopathy (CM) onset related to delivery, and investigate incidence rate for HF and cardiomyopathies related to delivery over time. Method All women 18 to 50 years registered in the National Patient Register (NPR) from 1st January 1997 to 31st December 2019 were included. Time of delivery was obtained from the Swedish Medical Birth Register (MBR), time of death from the Cause of Death Register. Women with HF, CM and peripartum cardiomyopathy (PPCM) were identified from the NPR with international classification codes for disease ICD-10: I50, I42, I43 and 090.3, used for the first time 90 days prior or 180 days after delivery, and other comorbidities. Patients were compared with five controls without HF or CM from the Total Population Register matched by age, year of delivery, and county. Linear regression was used to test trend changes in use of ICD codes. The impact of baseline characteristics for onset av HF, CM and PPCM in patient compared to controls is presented as odds ratio (OR). Body mass index (BMI) was registered at the beginning of pregnancy. Results Between 1997 and 2019 we identified 2 347 723 deliveries, and 694 women with HF, CM or PPCM, median age 33 (29; 37) years and 3 465 controls. Out of those 493 (71%) had HF, 201 (29%) had any CM and 195 (28.1%) had PPCM. Over time the incidence rate of all conditions increased significantly, se Figure 1. Median BMI at the start of pregnancy increased significantly over time in patients with HF from 22 (20;28) to 27 (23;32), beta 0.1323 (p = 0.0216). Compared to controls patients with congenital heart disease OR at 18.32 (10.04-33.41), valve disease OR at 22.65 (8.55-60.03), arrythmia OR at 7.45 (4.06-13.67), hypertension OR at 7.89 (4.26-14.63), diabetes mellitus type II OR at 8.07 (2.63-24.74) and gestational diabetes OR at 3.93 (2.54-6.07) (all p&amp;lt;0.001) to for HF, CM or PPCM onset related to delivery, also BMI &amp;gt;22,5 at the beginning of pregnancy, lower education level and income, se Figure 2. Conclusion Over 22 years we observed a significant increase in the incidence rate of HF and CM related to delivery. BMI already &amp;gt;22,5 was associated with higher risk for HF or any CM onset in relation to delivery.