Risk Factor For Heart Failure Research Articles

Age-Induced Accumulation of Succinate Promotes Cardiac Fibrogenesis.

Age-related cardiac fibrosis is a risk factor for heart failure and a marker for heart aging. However, the mechanisms underlying age-related cardiac fibrosis remain unclear. Ischemia and hypoxia are inevitable events in the aging process, which are direct causes of mitochondrial dysfunction and metabolic alterations. In this study, we identified metabolic changes and determined the mechanisms by which succinate (a tricarboxylic acid cycle intermediate) accumulation promotes fibroblast activation and apoptosis resistance in the aging heart. We also assessed its significance in relation to cardiac fibrosis and diastolic dysfunction. We first investigated how aging promotes persistent cardiac fibrosis. Following this, the metabolic alterations of the aging heart were identified by untargeted metabolomics, and the succinate level was verified via quantitative analysis. Furthermore, the correlations between succinate and fibrosis or diastolic dysfunction in older mice/people were assessed. We also described the role of succinate and its receptor SUCNR1/GPR91 in establishing a fibrosis network during diastolic dysfunction with age using SUCNR1-/- mouse model and an AAV9-based approach. We further identified the specific mechanisms involved in PKM2 dimerization, which regulate fibroblast activation and apoptosis resistance. We demonstrated that aging promotes fibrogenesis and diastolic dysfunction, which are linked to fibroblast activation and apoptosis resistance in the heart. Succinate levels were correlated with diastolic dysfunction and cardiac fibrosis in older mice and people. Functionally, succinate promoted fibroblast activation and apoptosis resistance, which aggravate cardiac fibrosis formation in both young and old mice. This was attributed to the ability of succinate to stimulate PKM2 dimerization via succinate receptor SUCNR1. Furthermore, dimeric PKM2 translocated to the nucleus and mitochondria, where it promoted fibroblast activation and apoptosis resistance, respectively. Accumulated PKM2 in the nucleus interacted with HIF-1α, increasing the DNA binding of HIF-1α and the expression of fibrogenic genes, resulting in fibroblast activation. In the mitochondria, accumulated PKM2 phosphorylated VDAC1 at T93 and increased VDAC1 degradation by promoting SYVN1-based E3 ligase binding to VDAC1, which is associated with increased apoptosis resistance and fibrosis persistence. We found that targeting succinate accumulation by metformin can inhibit fibroblast activation and apoptosis resistance in mice, which is a potential strategy to control age-related cardiac fibrosis and diastolic dysfunction. Our findings indicate that targeting metabolic dysregulation has significant implications for the treatment of age-related cardiac fibrosis and diastolic dysfunction. We further demonstrate a novel mechanism by which succinate induces fibroblast activation and apoptosis resistance by promoting PKM2 dimerization. Hence, inhibiting succinate generation or blocking its downstream effects is potentially a promising new strategy for slowing the heart aging.

Establishment and validation of a prediction nomogram for heart failure risk in patients with acute myocardial infarction during hospitalization

BackgroundAcute myocardial infarction (AMI) with consequent heart failure is one of the leading causes of death in humans. The aim of this study was to develop a prediction model to identify heart failure risk in patients with AMI during hospitalization.MethodsThe data on hospitalized patients with AMI were retrospectively collected and divided randomly into modeling and validation groups at a ratio of 7:3. In the modeling group, the independent risk factors for heart failure during hospitalization were obtained to establish a logistic prediction model, and a nomogram was constructed. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the predictive performance and clinical value. Machine learning models with stacking method were also constructed and compared to logistic model.ResultsA total of 1875 patients with AMI were enrolled in this study, with a heart failure rate of 5.1% during hospitalization. The independent risk factors for heart failure were age, heart rate, systolic blood pressure, troponin T, left ventricular ejection fraction and pro-brain natriuretic peptide levels. The area under the curve (AUC) of the model in modeling group and validation group were 0.829 and 0.846, respectively. The calibration curve showed high prediction accuracy and the DCA curve showed good clinical value. The AUC value of the ensemble model by the stacking method in the validation group were 0.821, comparable to logistic prediction model.ConclusionsThis model, combining laboratory and clinical factors, has good efficacy in predicting heart failure during hospitalization in AMI patients.

Association of serum Asprosin concentrations with heart failure

BackgroundTo analyze the association of serum Asprosin concentrations with heart failure (HF).MethodsA total of 103 patients with HF were included in the HF group, and 103 patients with health checkups were included in the non-HF group. The serum Asprosin levels of the two groups were measured, and relevant clinical data were collected for statistical analysis.ResultsCompared with the non-HF group, the serum Asprosin concentration was significantly higher in the HF group, and the difference was statistically significant (P < 0.001). According to the serum Asprosin levels, we divided all the subjects into three quartiles. We found that the prevalence of HF increased with increasing serum Asprosin levels in the three groups (P < 0.001). Serum Asprosin levels were positively correlated with NT-ProBNP (P < 0.05) and negatively correlated with LVEF (P < 0.001). Dichotomous logistic regression analysis found Asprosin and age to be independent risk factors for HF (OR = 1.010, 95% CI: 1.003–1.018; OR = 1.058, 95% CI:1.004–1.665, respectively). Combining Asprosin and NT-proBNP indicators to draw ROC curves can improve the specificity and sensitivity of HF diagnosis.ConclusionsSerum Asprosin levels were significantly elevated in HF patients. The serum Asprosin level is an independent risk factor for HF, and the combined detection of Asprosin and NT-proBNP levels can improve the accuracy of HF diagnosis.

Rediscover the predictive capacity of B-type natriuretic peptide applied to neonatal supraventricular tachycardia

BackgroundSupraventricular tachycardia (SVT) is one of the most common non-benign arrhythmias in neonates, potentially leading to cardiac decompensation. This study investigated the early risk factors of acute heart failure (AHF) secondary to SVT in neonates, and explored their value in guiding the selection of effective anti-arrhythmic treatment.MethodsA total of 43 newborns diagnosed with and treated for SVT between January 2017 and December 2022 were analyzed. According to the presence of AHF after restoring sinus rhythm in newborns with SVT, they were divided into SVT with AHF group and SVT without AHF group. Clinical data and anti-arrhythmic therapies were analyzed. Risk factors of AHF secondary to SVT in neonates were determined using logistic regression. The cut-off value for predictors of AHF secondary to SVT and demanding of a second-line anti-arrhythmic treatment was determined through receiver operating characteristic (ROC) analysis.ResultsTime to initial control of tachycardia > 24 h, hyperkalemia, anemia, and plasma B-type natriuretic peptide (BNP) were identified as risk factors of AHF secondary to SVT in neonates. BNP exhibited AUC of 0.80 in predicting AHF, and BNP > 2460.5pg/ml (OR 2.28, 95% CI 1.27 ~ 45.39, P = 0.03) was an independent predictor, yielding sensitivity of 70.6% and specificity of 84.6%. Neonates with BNP > 2460.5pg/ml (37.5% versus 7.4%, P = 0.04) had a higher demand for a second line anti-arrhythmic treatment to terminate SVT, with sensitivity and specificity for BNP in predicting at 75.0%, 71.4%, respectively.ConclusionsBNP could be used to predict an incident of AHF secondary to SVT and a demand of second-line anti-arrhythmic treatment to promptly terminate SVT and prevent decompensation in neonates.

Identification and exploration of aging-related subtypes and distinctive role of SERPINE1 in heart failure based on single-cell and bulk RNA sequencing data.

Aging is a major risk factor for heart failure (HF) and is the leading cause of death worldwide. Currently, the nature of the relationship between aging and HF is not entirely clear. Herein, this study aimed to explore new diagnostic biomarkers, molecular typing and therapeutic strategies for HF by investigating the biological significance of aging-related genes in HF. A total of 157 differentially expressed genes (DEGs) were screened totally between HF and normal samples, and functional enrichment analysis of DEGs revealed the strong association of HF progression with aging, immune processes and metabolism. Six HF-specific aging-related genes were further identified, and a diagnostic model was developed and validated for good diagnostic efficacy. In addition, we collected blood samples from 10 normal controls and 10 HF patients for RT-qPCR analysis to verify the bioinformation. We also identified two aging-associated subtypes with distinctly different immune infiltration and metabolic microenvironment. Further single-cell sequencing analysis conducted in the study identified SERPINE1 as a key gene in HF. The distinctive role of SERPINE1 fibroblasts was revealed, including three main findings: (I) fibroblasts had a higher proportion and expression of SERPINE1 levels in HF; (II) the ligand-receptor pair MDK-LRP1 made the most contributions in high interactions with other cell types in SERPINE1 fibroblasts; and (III) SERPINE1 fibroblasts were associated with the interaction of extracellular matrix and receptor and may be regulated by the transcription factor EGR1. In conclusion, this study highlights the importance of aging-related genes in diagnosing HF and regulating immune infiltration. We also identified different HF subtypes and a potentially crucial gene, which may provide a better understanding of the molecular-level mechanisms of aging-related HF and aid in developing effective therapeutic strategies.

Investigating the Smoker's Paradox: Aortic Stenosis Patient Outcomes in Smokers

BackgroundSmoking is a major risk factor for premature atherosclerosis, myocardial infarction (MI), heart failure (HF), and sudden cardiac death. Studies suggest that smokers lose at least a decade of life expectancy compared to non-smokers. Despite these well-documented risks, the short-term mortality rates following acute coronary syndromes (ACSs) or related HF are lower in current smokers than non-smokers, a phenomenon known as the smoker's paradox. This study aimed to examine the influence of smoking on in-hospital outcomes for patients diagnosed with aortic stenosis (AS) in the United States and ascertain the presence of the smoker's paradox in this patient population. MethodsIn this study, we utilized the National Inpatient Sample (NIS) for the year of 2020 to identify all patients who were admitted for a principal diagnosis of aortic stenosis (AS). Subsequently, we isolated those patients with an ICD-10 code indicating smoking or tobacco use. To examine associations, both logistic and linear regression analyses were employed while adjusting for potential confounding factors. Our findings were considered significant if the 2-tailed p-value was 0.05 or lower. ResultsIn 2020, there were 102,615 hospitalizations with a principal diagnosis of aortic stenosis, 41,689 (40.6%) of these cases involved patients with a secondary diagnosis of smoking history or use. After accounting for factors such as age, race, gender, hospital bed size, location, teaching status, insurance coverage, income level, and Elixhauser comorbidities, we found that patients who smoked and had AS demonstrated a lower rate of in-hospital mortality (aOR 0.64, 95% CI 0.51 – 0.81), mechanical ventilation (aOR 0.77, 95% CI 0.67- 0.88), vasopressor initiation (aOR 0.79, 95% CI 0.64- 0.95), mechanical circulatory support (aOR 0.56, 95% CI 0.34-0.91), and hemodialysis initiation (aOR 0.56, 95% CI 0.47-0.67) when compared to non-smoking patients with AS (Figure 1). ConclusionOur study demonstrated that patients with a primary diagnosis of aortic stenosis (AS) and a history of smoking or tobacco use had significantly lower odds of in-hospital mortality, mechanical ventilation, vasopressor use, mechanical circulatory support, and hemodialysis initiation compared to their non-smoking counterparts with AS. To comprehensively understand the smoker's paradox and its influence on clinical outcomes for patients hospitalized with AS, it is crucial to carry out larger, methodologically rigorous investigations. Such studies will aid in revealing the underlying mechanisms and reasons behind the persistence of this paradox, despite its apparent contradiction, ultimately enhancing our understanding and informing more effective patient care strategies.

Combination Electroacupuncture and Guidelines Directed Medical Therapy Maintained Stability of Heart Rate and Mean Arterial Pressure in Heart Failure with Reduced Ejection Fraction.

Clinical studies have shown that electroacupuncture (EA) has therapeutic and modulatory effects on managing heart failure (HF) risk factors. This study aimed to determine the impact of combination drugs and EA on chronic HF patients with reduced ejection fraction (HFrEF) to maintain a stable heart rate (HR) and mean arterial pressure (MAP). This single-blind clinical randomized controlled trial included 42 patients with chronic HFrEF. The patients were divided into 3 groups: patients taking drugs and EA, patients taking drugs and sham EA (sham acupuncture [SA]), and patients taking drugs without EA. All patients underwent 16 sessions of therapy for 8 weeks. There was a significant difference in the average MAP based on therapy duration in the drugs + EA group, whereas there was no significant difference between drugs + SA and drugs without EA groups. There was a substantial difference between the average MAP in the drugs + EA group at the beginning of therapy compared with that at midtherapy (P < 0.05) and at the beginning of treatment and at the end of therapy (P < 0.05). There was no significant difference in the mean HR between the groups. Clinically, after 16 treatment sessions, patients receiving combined drugs and EA treatment presented with stable MAP and HR. Drugs combined with EA maintained the stability of MAP and HR in patients with chronic HFrEF.

Short-term paroxysmal atrial fibrillation detection with intra- and inter-patient paradigm based on R-R intervals

Paroxysmal Atrial Fibrillation (PAF) may lead to the decline of atrial mechanism and hemodynamic disturbance, which is the major risk factor for stroke, myocardial infarction, heart failure and other diseases. Although a number of methods have been developed to detect PAF, they rely on long ECG signals. Furthermore, most studies are only for the intra-patient test, ignoring individual specificity. Therefore, this paper proposes an automatic detection algorithm based on the combination of RR interval time-domain and nonlinear features to detect short-term PAF. The proposed features reflect the underlying physiological phenomenon of highly irregular ventricular activity caused by atrial unstable conduction. These include changes in morphological features and intrinsic changes in the cardiac dynamic system, which can capture subtle changes in early short-term PAF episodes and attenuate specificity between individuals. Finally, the random forest algorithm was used to detect the MIT-BIH Atrial Fibrillation Database and MIT-BIH Arrhythmia Database with intra-patient and inter-patient paradigm. The results show that the two databases’ algorithm accuracy in different paradigms of intra-patient and inter-patient have achieved more than 99.50% and 95.50%, respectively. Therefore, the proposed algorithm has a potential application for clinical monitoring.

Beyond Glycemic Control: Mechanistic Insights Into SGLT-2 Inhibitors in Heart Failure Management.

Heart failure is a common and clinically significant cardiac condition that causes significant morbidity and mortality in the United States. Diabetes and hypertension are 2 of the most common comorbidities associated with heart failure. Other risk factors for heart failure include smoking, obesity, and intrinsic cardiac diseases such as myocardial infarction and valvular pathologies. All of these conditions, to some extent, cause remodeling within the cardiomyocyte, which eventually leads to the development of congestive heart failure. Over the years, using diuretics and medications that inhibit the Renin-Angiotensin-Aldosterone System has been the traditional treatment for congestive heart failure. But in recent years studies in the diabetic population revealed that sodium-glucose cotransporter-2 inhibitors had a negative impact on the remodeling of cardiomyocytes. In this review, we discuss the numerous molecular mechanisms by which these recently developed medicines inhibit remodeling in cardiomyocytes, independent of their intended effect of decreasing blood glucose levels. Furthermore, it emphasizes the use of these drugs in diabetic as well as non-diabetic patients as a promising adjunct to ongoing heart failure treatment.

Sex difference in incidence and risk factors of hospitalization for heart failure, and subsequent mortality: findings from the China PEACE million persons project.

Epidemiological study of sex differences in incidence and risk factors of heart failure (HF), and subsequent mortality attributed to HF in the Chinese general population is lacking. This study aims to assess the sex differences in the incidence and risk factors of hospitalization for HF and evaluate the sex differences in population attributable fractions (PAFs) for the subsequent mortality among the general population. Data were from a sub-cohort of the Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project in China. Fine and Gray models were conducted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) accounting for the competing risk of all-cause mortality. Propensity score matching analysis and subgroup analyses were used to verify the robustness of the results. Adjusted PAFs of HF for all-cause and cardiovascular mortality were evaluated by sex. Of the 102,278 participants, 60.5% were women, and the mean age was 54.3 years. After a median follow-up of 3.52 years, 1588 cases of hospitalization for HF were identified. After adjusting for the covariates, women had 31% (95% CI: 0.61-0.79) lower risk for HF than men. The results were consistent in the propensity score matching cohort and across all subgroup analyses (all P sex-subgroups interaction > 0.05). Although women were associated with a lower risk of HF, they had a higher PAF (24.2%, 95% CI: 16.0-31.6) for subsequent cardiovascular mortality than men (16.5%, 95% CI: 11.3-21.5). Several significant differences in risk factors for HF were noted between sexes. In the southern Chinese population, women had a lower risk of HF but had a higher cardiovascular mortality fraction attributed to HF than men. Sex-specific preventative strategies and management for HF should be warranted.

Resolved Proteinuria May Attenuate the Risk of Heart Failure: A Nationwide Population-Based Cohort Study.

Although proteinuria is a risk factor for heart failure (HF), proteinuria can be reversible or persistent. Our objective was to explore the link between changes in the proteinuria status and the risk of HF. We included participants from a Korean national health screening cohort who underwent health examinations in 2003-2004 and 2005-2006 and had no history of HF. Participants were categorized into four groups: proteinuria-free, proteinuria-resolved, proteinuria-developed, and proteinuria-persistent. The outcome of interest was the occurrence of HF. The study included 1,703,651 participants, among whom 17,543 (1.03%) were in the proteinuria-resolved group and 4585 (0.27%) were in the proteinuria-persistent group. After a median follow-up period of 14.04 years (interquartile range 14.19-15.07), HF occurred in 75,064 (4.41%) participants. A multivariable Cox proportional hazards regression analysis indicated that the proteinuria-persistent group had a higher risk of HF compared with the proteinuria-free group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 2.03-2.36, p < 0.001). In a further pairwise comparison analysis, participants in the proteinuria-resolved group had a relatively low risk of HF compared with those in the proteinuria-persistent group (HR: 0.64, 95% CI: 0.58-0.70, p < 0.001). In conclusion, the risk of HF can change with alterations in the proteinuria status.

Acute heart failure following pazopanib treatment: a literature review featuring two case reports.

Tyrosine kinase inhibitors (TKIs) have transformed cancer treatment but are associated with cardiovascular toxicity, including heart failure. This review examines the cardiotoxicity of pazopanib, a VEGFR-TKI, through two case reports and explores potential mechanisms. The importance of vigilant clinical monitoring to prevent cardiac dysfunction in cancer patients receiving pazopanib is emphasized. We present two cases of acute heart failure following pazopanib treatment. Case 1 involves a comorbidity-free, 62-year-old woman with metastatic renal cell carcinoma who experienced irreversible heart failure. In case 2, a 40-year-old woman with a history of anthracycline-containing chemotherapy developed reversible left ventricular systolic dysfunction following pazopanib discontinuation. Both patients received appropriate management for their heart failure symptoms. Case 1's condition rapidly deteriorated, leading to her unfortunate demise 3 months after starting pazopanib. In contrast, case 2's cardiac function improved after discontinuing pazopanib. The advent of TKIs has revolutionized cancer treatment, but their association with cardiovascular toxicity necessitates meticulous monitoring of patients. The cases presented here highlight the importance of recognizing and managing cardiotoxicity, particularly in patients without prior cardiovascular risk factors. Understanding the underlying mechanisms and risk factors for TKI-induced heart failure is crucial to optimize patient care and treatment outcomes. Oncologists should be vigilant in identifying clinical symptoms and closely monitoring cardiac function throughout TKI therapy.

The importance, consequences and treatment of psychosocial risk factors in heart disease: less conversation, more action!

Psychosocial factors play asignificant role in the incidence and prognosis of cardiovascular disease with arapidly increasing body of knowledge, as acknowledged by their inclusion in the European Society of Cardiology cardiovascular prevention guideline since 2012. Nevertheless, psychosocial risk is not consistently assessed, acknowledged and treated in daily clinical practice. Therefore, adopting amultidimensional approach that encompasses biological, psychological, and social factors is crucial for understanding the dynamic nature of cardiovascular health and disease, delivering patient-centred care, and developing effective interventions to ultimately enhance health and satisfaction with contemporary medicine and care. The current review summarises the state-of-the-art evidence for screening and treating psychological risk factors in coronary heart disease, heart failure, and atrial fibrillation in the context of cardiac rehabilitation, along with accompanying recommendations. The limited adoption of routine screening, despite longstanding recommendations, highlights the importance of prioritising the implementation and expansion of routine screening in primary and secondary prevention. To advance psychosocial treatment, astandardised and personalised approach including comprehensive education, physical exercise, and psychosocial support with afocus on patient-reported outcomes is crucial. Treating heart and mind together has the potential to decrease psychosocial risk while enhancing the prognosis and quality of life, therefore delivering true patient-centred care.

Nocturnal Hypertension and Left Ventricular Diastolic Dysfunction in Patients With Diabetes With the Absence of Heart Failure: Prospective Cohort HSCAA Study.

Diabetes is an important risk factor for heart failure (HF) and is associated with left ventricular (LV) diastolic dysfunction. However, diabetic comorbid conditions, such as nocturnal hypertension, as predictors of diastolic dysfunction are not known in the absence of an HF period. The present study was conducted as the longitudinal examination of the predictive value of nocturnal hypertension profiles on the progression of LV diastolic dysfunction in patients with and without diabetes without HF. The subjects (154 diabetes and 268 nondiabetes) in the absence of HF were followed for 36.8±18.2 months. The relationships among the patterns of nocturnal hypertension and the outcome of LV diastolic dysfunction, defined as an increase in E/e'>14, were investigated in the patients with and without diabetes. The interaction effect of the diabetes status and the patterns of nocturnal hypertension on the hazard rate of the occurrence of E/e'>14 was statistically significant (P=0.017). Kaplan-Meier analysis results revealed that patients with diabetes with nondipper (P=0.021 versus dipper) and riser (P=0.006 versus dipper) had a greater risk for a diastolic dysfunction event. Furthermore, multivariable Cox proportional hazards analysis revealed that nondipper (hazard ratio, 4.56 [95% CI, 1.49-13.96]; P=0.007) and riser (hazard ratio, 3.89 [95% CI, 1.31-11.57]; P=0.014) patterns were associated with elevated risk of the outcome of LV diastolic dysfunction. In contrast, no similar significant associations were found in patients without diabetes. During the absence of HF periods, nocturnal hypertension is an important predictor for the progression of LV diastolic dysfunction in patients with diabetes.

Machine learning identification of risk factors for heart failure in patients with diabetes mellitus with metabolic dysfunction associated steatotic liver disease (MASLD): the Silesia Diabetes-Heart Project

BackgroundDiabetes mellitus (DM), heart failure (HF) and metabolic dysfunction associated steatotic liver disease (MASLD) are overlapping diseases of increasing prevalence. Because there are still high numbers of patients with HF who are undiagnosed and untreated, there is a need for improving efforts to better identify HF in patients with DM with or without MASLD. This study aims to develop machine learning (ML) models for assessing the risk of the HF occurrence in patients with DM with and without MASLD.Research design and methodsIn the Silesia Diabetes-Heart Project (NCT05626413), patients with DM with and without MASLD were analyzed to identify the most important HF risk factors with the use of a ML approach. The multiple logistic regression (MLR) classifier exploiting the most discriminative patient’s parameters selected by the χ2 test following the Monte Carlo strategy was implemented. The classification capabilities of the ML models were quantified using sensitivity, specificity, and the percentage of correctly classified (CC) high- and low-risk patients.ResultsWe studied 2000 patients with DM (mean age 58.85 ± SD 17.37 years; 48% women). In the feature selection process, we identified 5 parameters: age, type of DM, atrial fibrillation (AF), hyperuricemia and estimated glomerular filtration rate (eGFR). In the case of MASLD( +) patients, the same criterion was met by 3 features: AF, hyperuricemia and eGFR, and for MASLD(−) patients, by 2 features: age and eGFR. Amongst all patients, sensitivity and specificity were 0.81 and 0.70, respectively, with the area under the receiver operating curve (AUC) of 0.84 (95% CI 0.82–0.86).ConclusionA ML approach demonstrated high performance in identifying HF in patients with DM independently of their MASLD status, as well as both in patients with and without MASLD based on easy-to-obtain patient parameters.Graphical

Sex- and age-related differences in the inflammatory properties of cardiac fibroblasts: impact on the cardiosplenic axis and cardiac fibrosis.

Age and sex are prominent risk factors for heart failure and determinants of structural and functional changes of the heart. Cardiac fibroblasts (cFB) are beyond their task as extracellular matrix-producing cells further recognized as inflammation-supporting cells. The present study aimed to evaluate the impact of sex and age on the inflammatory potential of cFB and its impact on the cardiosplenic axis and cardiac fibrosis. Left ventricles (LV) of 3- and 12-months old male and female C57BL/6J mice were harvested for immunohistochemistry, immunofluorescence and cFB outgrowth culture and the spleen for flow cytometry. LV-derived cFB and respective supernatants were characterized. LV-derived cFB from 3-months old male mice exhibited a higher inflammatory capacity, as indicated by a higher gene expression of CC-chemokine ligand (CCL) 2, and CCL7 compared to cFB derived from 3-months old female mice. The resulting higher CCL2/chemokine C-X3-C motif ligand (Cx3CL1) and CCL7/Cx3CL1 protein ratio in cell culture supernatants of 3-months old male vs. female cFB was reflected by a higher migration of Ly6Chigh monocytes towards supernatant from 3-months old male vs. female cFB. In vivo a lower ratio of splenic pro-inflammatory Ly6Chigh to anti-inflammatory Ly6Clow monocytes was found in 3-months old male vs. female mice, suggesting a higher attraction of Ly6Chigh compared to Ly6Clow monocytes towards the heart in male vs. female mice. In agreement, the percentage of pro-inflammatory CD68+ CD206- macrophages was higher in the LV of male vs. female mice at this age, whereas the percentage of anti-inflammatory CD68+ CD206+ macrophages was higher in the LV of 3-months old female mice compared to age-matched male animals. In parallel, the percentage of splenic TGF-β+ cells was higher in both 3- and 12-months old female vs. male mice, as further reflected by the higher pro-fibrotic potential of female vs. male splenocytes at both ages. In addition, female mice displayed a higher total LV collagen content compared to age-matched male mice, whereby collagen content of female cFB was higher compared to male cFB at the age of 12-months. Age- and sex-dependent differences in cardiac fibrosis and inflammation are related to age- and sex-dependent variations in the inflammatory properties of cardiac fibroblasts.

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.

Sacubitril/Valsartan in Heart Failure with Hypertension Patients: Real-World Experiences on Different Ages, Drug Doses, and Renal Functions.

Hypertension is a significant risk factor in heart failure for worldwide patients. More than half of hypertensive patients suffer from heart failure. Recently, sacubitril/valsartan (sac/val) has been approved as an antihypertensive agent in China and Japan. Additionally, it is not approved for treating hypertension in Europe or the USA. To accumulate more real-world experiences to investigate the effectiveness and optimize clinical medication of sac/val in hypertensive patients with heart failure. We retrospectively enrolled adult patients diagnosed with hypertension (HTN) and heart failure (HF) and newly treated with sac/val. The baseline characteristics and clinical outcomes were retrospectively extracted from electronic medical records (EMR) in three centers. The efficacy and safety of sac/val were first analyzed in all enrolled patients. Stratified analyses were conducted in patients with different ages (≥ 65, < 65), maximum tolerated doses (≥ 200mg/days, < 200mg/days), and renal functions (e-GFR ≥ 60 ml/min/1.73 m2, < 60 ml/min/1.73 m2). Overall, 794 patients diagnosed with both HF and HTN were included in our study. During follow-up, significant reductions were found in blood pressure (BP) (SBP 12.8 ± 21.2 mmHg, P < 0.001, DBP 7.1 ± 16.5 mmHg, P < 0.001), and cardiac biomarkers (cardiac troponin 1.78 ± 19.1 ng/mL, P < 0.001, NT-proBNP 1403 ± 6937 pg/mL, P < 0.001) from baseline. In stratification analyses, the lower dosage group earned a higher BP control rate (83.4% vs. 75.6%, P = 0.025) and an overall improvement rate of cardiac indicators (61.3% vs. 48.0%, P = 0.002). The younger patients' group had significantly less cumulative hazard of recurrent cerebral-cardiovascular events than the elder group (log-rank P value < 0.001). Patients with renal dysfunction were observed with more AE incidences. Sac/val could reduce BP and improve cardiac structural and functional parameters in hypertensive patients with HF, even with less than target doses. However, more attention should be paid to older patients and renal dysfunction patients when using sac/val because of additional risks in adverse events.

Impact of Atrial Fibrillation on Heart Failure in Patients Treated With Anthracycline Chemotherapy

Atrial fibrillation (AF) and anthracyclines are known risk factors for heart failure (HF). The magnitude of the effect of preexisting AF (preanthracycline AF) and newly developed AF (postanthracycline AF) in patients treated with anthracyclines on the occurrence of HF is unknown. The aim of our study was to characterize the impact of preanthracycline and postanthracycline AF on the subsequent occurrence of HF in patients treated with anthracyclines. In 5,598 patients treated with new anthracycline therapy at a tertiary center between 2008 and 2021, propensity score matching was used to match 204 pairs with or without preanthracycline AF and 135 pairs with or without postanthracycline AF. The primary outcome was new-onset symptomatic HF defined by the American Heart Association/American College of Cardiology guidelines. Patients with and without preanthracycline and postanthracycline AF were well matched for age, gender, medications, and cardiovascular risk factors. A total of 45 patients with preanthracycline AF and 23 matched patients developed HF (5-year cumulative incidence: 29% in the preanthracycline AF group and 13% in the matched group, p=0.003; hazard ratio 2.1, 95% confidence interval 1.3 to 3.4, p=0.004). A total of 161 patients (2.9%) developed postanthracycline AF. A total of 39 patients (5-year cumulative incidence: 40%) with postanthracycline AF and 9 matched patients (5-year cumulative incidence: 7%) developed HF (hazard ratio 6.1, 95% confidence interval 3.0 to 12.4, p <0.001). Preanthracycline AF and postanthracycline AF are associated with a high incidence of subsequent HF in patients treated with anthracyclines. Prospective studies of therapies are required to decrease HF in these high-risk patients.

Impaired retinal micro-vascular function in patients with atrial fibrillation

BackgroundCardiovascular (CV) risk factors and CV diseases, in particular heart failure, are strongly associated with impaired microvascular retinal endothelial function. Whether atrial fibrillation (AF) contributes to vascular dysfunction is not clear. Therefore, the aim of this study was to investigate the impact of AF on retinal microvascular function. MethodsIn this study, vascular function was measured non-invasively with flicker-light induced vasodilatation of retinal arterioles (FIDart%). Patients with a history of AF and risk factors for heart failure (HF) or heart failure (n = 69; age 67.9 ± 9.2 years, 71% male, 35% HFrEF, 56% paroxysmal, 25% persistent, 19% permanent AF), as well as age, sex and ejection fraction matched patients with absent history of AF (n = 66; age 63.4 ± 10.6 years, 67% male, 47% HFrEF) were included. Patients with AF were further divided into those with paroxysmal AF (in sinus rhythm – AFSR: n = 38, age 71.4 ± 9.2, 73% male), and those with AF at the time of the study visit. ResultsRetinal microvascular function was impaired in patients with AF compared to patients without AF (FIDart% 1.1% [0.3–2.8] vs. 2.7% [1.3–5.1], p < 0.001). Patients currently in AF have poorer retinal microvascular function (FIDart% 0.8% [0.1–1.9) compared to patients with a history of AF but currently in SR at the time of retinal function measurement (1.5% [0.6–4.9] p = 0.017). In patients with AF, impaired retinal vascular function was independently associated with larger left atrial volume (mean 49.8 ± 18.4), even after correction for confounding factors in different models (SCR = -0. 251 to −0.256, p = 0.035–0.01). ConclusionsAF in patients with heart failure is associated with impaired vascular function, even if currently in sinus rhythm. The association of retinal microvascular dysfunction with left atrial volume, a surrogate for elevated cardiac filling pressures, may further highlight the important interplay between the vasculature and elevated filling pressures in the development of AF.