Development Of Heart Failure Research Articles

Role of PGC-1α in the proliferation and metastasis of malignant tumors.

Malignant tumors are among the major diseases threatening human survival in the world, and advancements in medical technology have led to a steady increase in their detection rates worldwide. Despite unique clinical presentations across the spectrum of malignancies, treatment modalities generally adhere to common strategies, encompassing primarily surgical intervention, radiation therapy, chemotherapy, and targeted treatments. Uncovering the genetic elements contributing to cancer cell proliferation, metastasis, and drug resistance remains a pivotal pursuit in the development of novel targeted therapeutics. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A/PGC-1α) is a transcriptional coactivator that influences most cellular metabolic pathways. Its aberrant expression is associated with numerous chronic diseases, including diabetes, heart failure, neurodegenerative disorders, and cancer development. This study primarily discusses the structure, physiological functions, regulatory mechanisms, and research advancement concerning the role of PGC-1α in the proliferation and metastasis of malignant tumors. Targeting PGC-1α and its related regulatory pathways for therapeutic interventions holds promise in facilitating precise and individualized oncological treatments. This approach is expected to counteract drug resistance in patients with cancer and offer a novel direction for the treatment of malignant tumors.

Dapagliflozin improves ejection fraction, radial/longitudinal strain and reduces systemic H-FABP and pro-inflammatory cytokines in models of dororubicin/trastuzumab induced cardiotoxicity

Abstract Background The use of anthracyclines as a standard cancer therapy is limited by the potential for the development of cardiac dysfunction, arrhythmias, and clinical heart failure. The incidence of cardiac dysfunction or heart failure post-trastuzumab plus anthracycline therapy is higher compared to monotherapy regimen, exposing cancer patients to cardiotoxic risk. Dapagliflozin exerts several cardiometabolic benefits in patients with and wthout T2DM through SGLT2-NLRP3 mediated pathways. In this study, we highlighted on new beneficial properties of Dapagliflozin in preclinical models of doxorubicin-HER-2 blocking agent induced cardiotoxicity. Methods Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg associated to HER-2 blocking agent i.p at 2,25 mg/kg (DOXO/TRA, n=6), DAPA at 12 mg/kg (DAPA, n=6) or doxorubicin-HER-2 blocking agent combined to DAPA (DOXO/TRA–DAPA, n=6). Cardiac function studies, including EF, FS and radial/longitudinal strain were analysed through transthoracic echocardiography (Vevo 2100) . Systemic levels of ferroptosis-related biomarkers, galectin-3, high-sensitivity C-reactive protein (hs-CRP), and pro-inflammatory chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. Results Dapagliflozin increased EF and FS compared to DOXO groups (p < 0.01), prevented the reduction of radial and longitudinal strain after 10 days of treatment with DOXO-TRA (RS) 40.2% in EMPA-DOXO vs 14.9% in DOXO-TRA mice; LS – 26,8 % in DOXO/TRA-DAPA vs – 9,7.3% in DOXO/TRA mice (p < 0.001 for both). Dapagliflozin associated to Doxorubicin reduces of 53,8 % plasma levels of H-FABP compared to DOXO group (p<0.001). Myocardial expression of H-FABP were also reduced, indicating cardioprotective properties of SGLT2i. Significant reductions in ferroptosis, xanthine oxidase expression, cardiac fibrosis and apoptosis in DAPA associated to DOXO/TRA were also seen. A reduced expression of systemic pro-inflammatory cytokines and NLRP3 was also seen in in DOXO/TRA-DAPA group compared to DOXO/TRA (p < 0.001). Conclusion For the first time, Dapagliflozin demonstrated significant improvements in cardiac functions and reductions of systemic H-FABP and troponin levels during doxorubicin associated to HER- blocking agent therapy, indicating new potential pathways of cardioprotection in cancer patients.

Improvement of right and left ventricular echocardiographic parameters in obese patients after bariatric surgery

Abstract Background Severe obesity causes hemodynamic changes in the circulatory system, which leads to the development of heart failure with either preserved or reduced ejection fraction. Weight loss achieved through bariatric surgery is likely to possibly reverse many of hemodynamic and structural abnormalities caused by obesity. Purpose Assessment of left and right ventricular function in patients undergoing bariatric surgery. Methods Detailed echocardiographic parameters assessing left and right ventricular function in severely obese patients undergoing bariatric surgery were analyzed. The following parameters of left and right ventricular function were compared in the examinations performed before, 3 and 6 months after surgery: left ventricular ejection fraction (LVEF), LV and RV global longitudinal strain (GLS), peak early (e’) and late (a’) diastolic annular velocities (lateral and septal) with calculation of E/e’ ratios, left atrium volumeindex ( LAVI), TRV (tricuspid regurgitation velocity), tricuspid annular plane systolic excursion (TAPSE), maximum systolic velocity of the lateral part of the tricuspid annulus-s’ and accelerated pulmonary time (AcT). Results Forty obese patients (76% women) with mean BMI 40.3 (SD 5.6) and mean age of 42.4 (SD 11.9) years were enrolled. BMI as 6 months was 31.2 (SD 5.1). Baseline and follow-up results of echocardiography are presented for both left and right ventricular parameters in Table 1 and Table 2. Conclusions Only GLS for right and left ventricle, FWS and TRV improve significantly within 6 months from bariatric surgery. On the other hand, these changes are significant as early as 3 months after bariatric surgery. Left ventricular parameters Right ventricular parameters

Risk estimation for subclinical heart failure using the PREVENT calculator in patients with autoimmune rheumatic diseases

Abstract Background Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and psoriatic arthritis (PsA) are heterogeneous autoimmune diseases with established cardiovascular involvement associated with a higher risk of developing heart failure (HF). Studies have shown a greater risk for HF in rheumatologic patients compared to the general population, however, the calculated risk varies among studies. PREVENTTM is the first cardiovascular risk calculator to predict the risk of HF. Purpose To evaluate the performance of the novel PREVENTTM cardiovascular risk calculator to detect subclinical HF in patients with inflammatory autoimmune diseases. Methods Cross-sectional, descriptive study involving RA, SLE, and PsA patients of a single cardiology-rheumatology preventive clinic in a tertiary-care hospital. This cohort includes patients aged 30-79 who met the ACR/EULAR/CASPAR classification criteria for diagnosing RA, SLE, and PsA, respectively. Exclusion criteria included a previous diagnosis of atherosclerotic cardiovascular disease, overlap syndromes, or pregnancy. The risk of heart failure was assessed using the new 10-year PREVENTTM calculator and patients were categorized as high risk if they had ≥20%. The result was multiplied by 1.5 according to EULAR 2015/2016 recommendations in the patients with RA. A transthoracic echocardiogram was performed on all participants by a board-certified cardiologist. Distribution was assessed by the Kolmogorov-Smirnov test. Results are shown as frequencies (%) for qualitative variables and mean ± SD or median (p25-p75) according to the distribution of quantitative variables. Cohen's Kappa coefficient was used to evaluate the agreement between the transthoracic echocardiogram and the PREVENTTM algorithm to detect subclinical HF. Results A total of 238 patients with rheumatic diseases were included, mostly women (n = 204, 85.7%) with a mean age of 52.8 ± 10.1 years. Demographic and clinical characteristics are shown in Table 1. The PREVENTTM calculator classified 4 (1.6%) patients of the 3 rheumatologic diseases as a high-risk category. Employing echocardiography, 144 (60.5%) patients with subclinical HF were identified. By Kappa analysis, a slight concordance was found in patients with RA (k = 0.033) and poor concordance in patients with SLE (k = -0.049) between the PREVENTTM algorithm and the echocardiogram for the classification of high-risk subclinical HF patients. No concordance was found in patients with PsA. Conclusion Our study demonstrates that the PREVENTTM risk algorithm failed to detect a high proportion of patients with subclinical HF and that there is no concordance between the two methods. Echocardiography as part of cardiovascular evaluation may help detect those patients with rheumatologic diseases and subclinical HF.

Cachectic biomarkers as confounders behind the obesity paradox in patients with acute decompensated heart failure.

Obesity is a risk factor for heart failure (HF) development but is associated with a lower incidence of mortality in HF patients. This obesity paradox may be confounded by unrecognized comorbidities, including cachexia. A retrospective assessment was conducted using data from a prospectively recruiting multicenter registry, which included consecutive acute heart failure patients. A low, normal, and high body mass index (BMI) was defined as <20 kg/m2, 20-25 kg/m2, and ≥25 kg/m2, respectively. Cachexia was defined as a combination of BMI < 20 kg/m2 and any biochemical abnormalities including albumin, hemoglobin, or C-reactive protein. Patients with either of the three biochemical abnormalities were categorized as those with cachectic biomarkers. Two-year all-cause, cardiac, and noncardiac mortality were evaluated. This study evaluated 3314 patients (mean BMI, 22 ± 4 kg/m2 [low BMI with cachexia, 828 (25%); low BMI without cachexia, 273 (8%); normal BMI, 1584 (48%); high BMI, 629 (19%)]). Overall, an increase of 1 point in BMI was associated with a decreased incidence of all-cause mortality (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.90-0.94; p < 0.001). Regardless of the mode of death, the low BMI with cachexia indicated the worst prognosis, while the low BMI without cachexia showed a similar prognosis to the normal BMI. Cachectic biomarkers, which were observed more frequently in the low BMI, predicted a higher incidence of 2-year all-cause mortality across the BMI categories (adjusted HR for the low BMI, 1.90; 95% CI, 1.30-2.77; p = 0.001; adjusted HR for the normal BMI, 1.94; 95% CI, 1.34-2.79; p < 0.001; adjusted HR for the high BMI, 3.60; 95% CI, 1.61-8.08; p = 0.002). BMI could be only a surrogate marker. The cachectic biomarkers may reflect the underlying conditions and contribute to elucidating the obesity paradox.

Meteorin-like protein plasma levels are associated with worse outcomes in de novo heart failure.

Meteorin-like protein (Metrnl) has been recently suggested as a new adipokine with protective cardiovascular effects. Its circulating levels in patients seem to be associated with heart failure (HF), although with contradictory results. Our aim was to ascertain whether this adipokine could estimate the prognosis of HF in de novo HF (DNHF) patients. Metrnl plasma levels of 400 patients hospitalized with DNHF (55% of patients with HF with reduced ejection fraction, 17.3% HF with mid-range ejection fraction, 27.8% HF with preserved ejection fraction) were measured by enzyme-linked immunosorbent assay. We performed both sex-pooled and sex-specific analyses. A 12-month follow-up was conducted, during which clinical outcomes such as all-cause mortality, cardiovascular death and re-hospitalization due to HF were collected. After a 12-month follow up, higher plasma Metrnl levels were associated with an increased risk for all-cause death and cardiovascular death after adjusting by sex, age, LVEF, hypertension, diabetes, ischemic aetiology, chronic renal failure, NT-proBNP and troponin (hazard ratio [HR] = 1.003, 95% confidence interval [CI] = 1.000-1.005; p-value<.05 and HR = 1.004, 95% CI = 1.001-1.007, p-value<.05, respectively). In line with this, DNHF patients with increased levels of circulating Metrnl had a higher number of occurrences of cardiovascular events. Regarding Metrnl associations with parameters implicated in the development and progression of HF, we found that Metrnl circulating levels were positively correlated with age (r = .322, p-value<.0001), NT-proBNP (r = .281, p-value<.0001) and with the renal dysfunction markers urea (r = .322, p-value<.0001) and creatinine (r = .353, p-value<.0001) and higher in women than men (473.7 [385.9-594.0] pg/mL vs. 428.7 [349.1-561.3] pg/mL, p-value<.006). Finally, concerning the subtype of HF, Metrnl plasma levels were higher in HF with preserved ejection fraction. Patients with higher Metrnl levels have a worse prognosis in DNHF. Our results reinforce the association of Metrnl plasma levels with HF progression and outcomes.

Alcohol consumption and incident heart failure in men and women.

Regular heavy alcohol consumption may lead to the development of alcohol-related cardiomyopathy and symptomatic heart failure (HF) later in life. However, the dose-response relationship between alcohol consumption and risk for incident HF, and whether these associations vary by sex and type of alcoholic beverage remains unclear. A total of 407 014 participants (52% women, age 56 years) from the UK Biobank who completed alcohol-related questionnaires and without a history of HF at baseline were included in the study. Competing-risk model and cubic spline regression analyses were used to calculate hazard ratios of the association between alcohol consumption and incident HF in men and women. The associations were adjusted for an extensive set of potential confounders. During a median follow-up of 12 years, 11 735 (34% women) cases of incident HF were identified. Total alcohol consumption was higher in men than in women (median consumption: 16 vs. 8 drinks/week, p < 0.001). A J-shaped association was observed between total alcohol consumption and incident HF in both men and women. Drinking alcohol <28 units/week was associated with a lower risk for developing HF, with a ~20% maximum risk reduction at 14 units/week in men and 7 units/week in women, independent of common confounders. Similar trends were observed in wine consumption. However, the risk of incident HF increases with beer consumption, particularly in women (p for sex interaction = 0.002). Consuming 7-14 units/week of beer was associated with a 29% increased risk of incident HF in women. Alcohol consumption was higher among men compared with women. Although low to moderate total alcohol consumption appears to be associated with a reduced risk of developed HF, beer drinkers, particularly women, were at higher risk of developed HF.

Downregulation of CCR2 reduces ventricular remodeling after myocardial infarction by splenic nerve neuromodulation in acute and chronic rat models.

Pathological remodeling after myocardial infarction (MI) confers the development of heart failure. Our prior research has indicated that splenic nerve neuromodulation mitigates myocardial ischemia-reperfusion injury (IRI) by reducing levels of proinflammatory factors. This study aims to explore the potential therapeutic benefits of splenic nerve neuromodulation in MI and the underlying mechanism. Splenic nerve neuromodulation was performed through electrical splenic nerve stimulation (SpNS). In the acute myocardial IRI model, post-mortem analyses encompassed RNA sequencing and a range of molecular biology techniques, with the application of CCR2 antagonists (RS-504393) to inhibit the CCR2. In the chronic MI model, rats underwent echocardiographic assessment four weeks post-MI, after which tissues were harvested. In the acute IRI model, the negative regulation of chemokines production pathway was enriched by RNA-seq, and SpNS reduced the levels of CCR2, CCL2, and CCL7. The administration of RS-504393 decreased cardiomyocyte apoptosis, reduced myocardial damage, and lowered proinflammatory cytokines levels following myocardial IRI. Additionally, SpNS was shown to inhibit oxidative stress, proinflammatory cytokine levels, and cardiac collagen deposition, as observed four weeks post-MI. SpNS also restrained sympathetic nerve remodeling and improved left ventricular function, in part by downregulating CCR2 in the chronic MI model. SpNS demonstrated significant improvements in cardiac function, reductions of cardiac remodeling and inhibitions of excessive sympathetic activation in the chronic MI model by downregulation of CCR2. Our study provides novel evidence that splenic nerve neuromodulation may serve as a potential therapeutic intervention in MI patients.

Adrenomedullin 2/Intermedin Exerts Cardioprotective Effects by Regulating Cardiomyocyte Mitochondrial Function.

Adrenomedullin 2 (AM2) plays critical roles in regulating blood pressure and fluid balance. However, the specific involvement of AM2 in cardiac hypertrophy has not been comprehensively elucidated, warranting further investigation into its molecular mechanisms and therapeutic implications. Cardiac hypertrophy was induced in adult mice lacking AM2 (AM2-/-) using transverse aortic constriction surgery. Comprehensive cardiac morphology, function, histology, and transcriptome/metabolome analyses were conducted. Signal transduction underlying AM2 stimulation in the cardiomyocytes was explored. The absence of endogenous AM2 led to the development of severe heart failure after transverse aortic constriction surgery, which was characterized by alterations in the mitochondrial morphology and function associated with glycolysis and the tricarboxylic acid cycle in the heart and cardiomyocytes of transverse aortic constriction-operated AM2-/- mice. AM2 stimulation was associated with the receptor-modifying factor RAMP2 (receptor activity-modifying protein 2), which primarily transduces signals through the MAPK pathway and affects the expression of genes involved in glycolysis, β-oxidation, and oxidative phosphorylation. The administration of exogenous AM2 alleviated heart failure following transverse aortic constriction. AM2 crucially regulates mitochondrial functions associated with the glycolysis and tricarboxylic acid cycles in the cardiomyocytes, thereby exerting a protective effect on the heart under pressure overload conditions.

CURRENT ISSUES OF MODELING HEART FAILURE AND MYOCARDIAL FIBROSIS IN RATS

HighlightsMethods for modeling heart failure in rats are classified into models requiring surgical intervention, toxic, genetic and autoimmune models, models based on the effects of physical factors, the use of special dietary regimens.It is impossible to single out a single ideal model, since the development of heart failure is a multifactorial process, it is preferable to use a combination of several methods.The correctness of the choice of the model and its compliance with the tasks of future research must be confirmed by combining several diagnostic methods for verifying myocardial fibrosis - laboratory, histological, instrumental. AnnotationDetailed study of the mechanisms of heart failure and its main pathogenetic factor, myocardial fibrosis, is required for developing new effective treatment strategies. The choice of an appropriate model is key for a reliable experimental study. The aim of the review is to systematize current data on methods for modeling heart failure in rats. The main advantages of these animals are high genetic, biochemical and physiological similarity with humans, ease of breeding, availability of maintenance, small size, while allowing for surgery. This article classifies the currently available rat models of heart failure, discusses their pathophysiological basis, timing of the formation of heart failure, clinical features, advantages and disadvantages of each experimental model. The authors have paid particular attention to methods developed by domestic scientists. Methods for assessing the developed myocardial fibrosis and the influence of drugs on its formation are considered. The study of heart failure requires reliable animal models to assess biochemical, functional, morphological changes in damaged myocardium, and controlled testing of new drugs. Should the necessity arise, specialists should use several methods simultaneously, whereas the choice of treatment strategy depends on the aim of the study.

Metabolic dysfunction-associated steatotic liver disease is associated with increased risks of heart failure.

Metabolic dysfunction-associated steatotic liver disease (MASLD), defined by steatotic liver disease (SLD) and cardiometabolic factors, is increasing in prevalence, but its association with heart failure (HF) is unclear. Patients with SLD without a history of HF from 2006 to 2021 were retrospectively included and were classified into MASLD and non-MASLD groups that were followed longitudinally. The primary outcome was the new development of HF, which was sub-classified by echocardiography. Multivariable and propensity score matching analyses were conducted to adjust for confounding factors. Overall, 26 676 patients with SLD were included, with a median age of 51 years and 71% classified as MASLD. During a median follow-up of 6 years, 429 (1.61%) patients developed HF, and 76% were HF with preserved ejection fraction (HFpEF). The risk of HF was significantly higher in patients with MASLD than in those without (sub-distribution hazard ratio [SHR] 2.59, 95% confidence interval [CI] 1.84-3.64) after adjustment of competing mortality. There was a dose-dependent increase in HF risks in patients with more cardiometabolic risk factors (SHR 1.12, 95% CI 1.04-1.22). MASLD was also associated with higher risk of HF-related hospitalization (SHR 2.30, 95% CI 1.31-4.04) and specifically, the risk of HFpEF (SHR 1.91, 95% CI 1.27-2.86). In propensity score-matched cohorts, MASLD was also associated with a 2.52-fold higher risk of HF. In patients with SLD, those with MASLD show a higher risk of HF, specifically HFpEF. Future studies are warranted to validate the association between HF and MASLD.

Cardiovascular Profile and Cardiovascular Imaging After Bariatric Surgery: A Narrative Review.

Background and Objectives: Up until now, behavioral interventions and pharmacological therapies were the main approach available for the management of obesity. Diet and exercise, when used as a singular therapeutic method, are inadequate for a successful outcome. Research shows promising results for the surgical treatment of obesity, especially in the area of bariatric surgery (BaS). The relevance of this study is the valuable analysis of the evolution of obese patients with increased cardiovascular risk. Materials and Methods: The patients eligible for BaS commonly suffer from multiple chronic conditions, including type 2 diabetes, obstructive sleep apnea, cardiovascular diseases, and non-alcoholic fatty liver disease. Additionally, obesity contributes to an increased probability of developing certain types of cancer, osteoarthritis, urinary incontinence, and chronic kidney disease. In this review, we focused especially on the cardiovascular status of obese patients who underwent bariatric procedures. Results: BaS has been found to be strongly associated with a reduced incidence of severe complications in individuals with a history of myocardial infarction (MI) and severe obesity. Specifically, this procedure is linked to a lower occurrence of major adverse cardiovascular events and a decrease in overall mortality. Also, BaS is correlated with a reduced risk of recurrent MI and the development of new-onset heart failure. Conclusions: The results of BaS involve a significant amelioration of the BMI, contributing to a considerable decrease in cardiovascular risk factors and to a notable refinement in the cardiovascular structure and function.

BTKi-induced cardiovascular toxicity in CLL: Risk mitigation and management strategies.

Targeted therapies, consisting of Bruton tyrosine kinase inhibitors (BTKis) or BCL-2 inhibitors, are the mainstay of contemporary treatments for chronic lymphocytic leukemia (CLL). The most common adverse effects (AEs) of BTKis are fatigue, bruising, infection, hematological and cardiovascular AEs. While AEs during treatment are usually mild (grades 1 and 2), grade 3 and 4 AEs have been detected in some patients, necessitating additional medical care and temporary or permanent drug discontinuation. In this review, we analyzed the cardiovascular effects associated with BTKi therapy for CLL and the essential practical aspects of multidisciplinary management of patients who develop cardiovascular toxicity during treatment. We particularly focus on the data and strategies for controlling cardiovascular risks associated with ibrutinib and newer BTKis (acalabrutinib, zanubrutinib and pirtobrutinib), including the development of atrial fibrillation, hypertension, ventricular arrhythmias, sudden death, heart failure, bleeding, and ischemic complications (stroke and myocardial infarction). This review highlights hematological insights underlying cardiotoxicity, an area that has received limited attention in comparison to the predominantly cardiological perspective. This review synthesizes emerging evidence on hematological biomarkers, cardiotoxic mechanisms, and therapeutic interventions, linking hematology and cardiology to enhance understanding and guide comprehensive prevention and management strategies.

Image-Based Estimation of Left Ventricular Myocardial Stiffness.

Elevation in left ventricular (LV) myocardial stiffness is a key remodeling-mediated change that underlies the development and progression of heart failure (HF). Despite the potential diagnostic value of quantifying this deterministic change, there is a lack of enabling techniques that can be readily incorporated into current clinical practice. To address this unmet clinical need, we propose a simple protocol for processing routine echocardiographic imaging data to provide an index of left ventricular myocardial stiffness, with protocol specification for patients at risk for heart failure with preserved ejection fraction. We demonstrate our protocol in both a preclinical and clinical setting, with representative findings that suggest sensitivity and translational feasibility of obtained estimates.

An Ovine Model of Chronic Heart Failure Induced by Repeated Coronary Microembolizations.

The use of large animals in research provides a unique bridge between preclinical findings and clinical relevance, offering a valuable perspective for advancing our understanding of the complexities of heart failure. Multiple models of heart failure have been established with advantages and limitations of each model. Many insights have been gained from these models for understanding both pathophysiological mechanisms and therapeutic interventions for heart failure. We have developed a chronic model of heart failure with reduced ejection fraction in sheep using the coronary microembolization technique. These animals gradually develop heart failure over a period of 3months. In this chapter, we document how this model can be established. The left main coronary artery is cannulated under fluoroscopic guidance, and polystyrene latex microspheres are injected into the artery. Up to three sequential selective microembolizations are undertaken over a period of 3weeks. Changes in ECG are monitored, and echocardiography is used to check on the progression of left ventricular dysfunction. All animals were followed for 3months after the first embolization, and heart tissue was examined to check for changes in cardiac myocyte size. All animals developed stable signs of HF. We propose that multiple sequential intracoronary microembolizations can induce stable myocardial dysfunction with hemodynamic signs of chronic heart failure.

Sex-specific risk factors for new-onset heart failure: the PREVEND study at 25 years.

Current estimates for the lifetime risk to develop heart failure with either a reduced (HFrEF) or preserved ejection fraction (HFpEF) and their associated risk factors are derived from two studies from the USA. The sex-specific lifetime risk and population attributable fraction of potentially modifiable risk factors for incident HFpEF and HFrEF are described in a large European community-based cohort with 25 years of follow-up. A total of 8558 participants from the PREVEND cohort were studied at baseline from 1997 onwards and followed until 2022 for cases of new-onset HFrEF (ejection fraction < 50%) and HFpEF (ejection fraction ≥ 50%) by assessment of hospital records. A total of 804 cases of new-onset HF were identified (534 HFrEF and 270 HFpEF) during 25 years of follow-up. The mean age at baseline was 50 years for men and 47 years for women. The mean age at onset of HF was 72.1 years in men and 74.2 years in women. The overall lifetime risk of developing HF was 24.5% in men compared to 23.3% in women. The lifetime risk of HFrEF was lower in women compared with men (11.9% vs. 18.1%), while the lifetime risk of HFpEF was higher in women compared with men (11.5% vs. 6.4%). In women, 71% of incident HFrEF cases were attributable to eight risk factors (hypertension, hypercholesterolaemia, obesity, smoking, atrial fibrillation, chronic kidney disease, myocardial infarction, and diabetes mellitus) and 60% in men. In women, 64% of incident HFpEF cases were attributable to those risk factors, whereas this was 46% in men. More specifically, in both men and women, hypertension and hypercholesterolaemia were the strongest risk factors for HFrEF, whereas hypertension and obesity were the strongest risk factors for HFpEF. In this European cohort, the lifetime risk of developing HFrEF was greater in men than in women, while women were at greater risk of developing HFpEF. Eight directly and indirectly modifiable risk factors substantially accounted for the risk of developing HFrEF and HFpEF, particularly in women.

High Salt Exacerbates Myocardial Dysfunction InVitro and InVivo by Promoting SIRT1/Nrf2-Mediated Ferroptosis.

Myocardial dysfunction is a crucial determinant of the development of heart failure in salt-sensitive hypertension. Ferroptosis, a programmed iron-dependent cell death, has been increasingly recognised as an important contributor to the pathophysiology of various cardiovascular diseases. This study aims to investigate the role and underlying mechanism of ferroptosis in high-salt (HS)-induced myocardial damage. Our results reveal that HS stimulation inhibited cell proliferation and promoted apoptosis in cardiomyocyte HL-1 cells in a dose-dependent manner. Ferroptotic features were observed in HS-induced HL-1 cells, including ferric iron accumulation, decreased glutathione levels, increased oxidative stress levels, upregulation of ferroptosis marker proteins PTGS2, 4HNE and FTH1 and downregulation of GPX4, all of which were reversed by treatment with the ferroptosis suppressor Fer-1. Furthermore, the administration of Fer-1 ameliorated HS-induced ferroptosis and myocardial damage in salt-sensitive Dahl SS rats. Additionally, we found that a HS diet suppressed the SIRT1/Nrf2 signalling pathway activation in our invivo experiments. Activation of SIRT1/Nrf2 signalling by SIRT1 overexpression significantly attenuated ferroptosis in HS-induced HL-1 cells. In conclusion, our findings demonstrate that HS levels induce myocardial injury by promoting ferroptosis via the deactivation of the SIRT1/Nrf2 signalling pathway, highlighting the potential for therapeutic targeting of ferroptosis for hypertension-related cardiovascular disorders.

Stress hyperglycaemia ratio is an independent predictor of in-hospital heart failure among patients with anterior ST-segment elevation myocardial infarction

BackgroundStress hyperglycaemia ratio (SHR) has been reported to be independently and significantly associated with various adverse cardiovascular events as well as mortality. Moreover, in-hospital heart failure following acute myocardial infarction has been demonstrated to account for majority of all heart failure (HF) cases with anterior myocardial infarction showing higher rates of HF. However, the association between SHR and in-hospital HF following an anterior ST-elevation myocardial infarction (STEMI) has not been reported earlier. Therefore, the present study aimed at identifying the relationship between SHR and in-hospital HF post STEMI.MethodsIn this retrospective study electronic health records of 512 patients who presented with anterior STEMI from 01 January 2022 to 31 January 2024 were analysed. Based on the development of in-hospital HF, the enrolled patients were stratified into two groups: Group I, comprising of 290 patients who developed in-hospital HF and Group II comprising of 222 patients who did not develop in-hospital HF. ROC and Multivariable logistic regression analyses were performed to assess the relationship between SHR and in-hospital HF.ResultsThe results revealed that SHR is a significant independent predictor of in-hospital HF (OR: 3.53; 95%CI: 2.02–6.15; p < 0.001). Apart from SHR, the results also identified age, nosocomial pneumonia, ventricular fibrillation, LVEF, and NT-pro-BNP levels as other independent predictors. ROC analysis showed that SHR independently had a moderate discriminative power with AUC: 0.683, 95% CI 0.605–0.762; p = 0.04, which was almost comparable to the combined predictive value of other independent risk factors (AUC: 0.726, 95% CI 0.677–0.784). Noticeably, combining SHR and other identified independent predictors demonstrated a significant predictive power (AUC: 0.813, 95% CI 0.757–0.881; p = 0.01).ConclusionSHR is an independent predictor for in-hospital HF in anterior wall STEMI patients.

Epicardial adipose tissue: a new link between type 2 diabetes and heart failure-a comprehensive review.

Diabetic cardiomyopathy is a unique cardiomyopathy that is common in diabetic patients, and it is also a diabetic complication for which no effective treatment is currently available. Moreover, relevant studies have revealed that a link exists between type 2 diabetes and heart failure and that abnormal thickening of EAT is inextricably linked to the development of diabetic heart failure. Numerous clinical studies have demonstrated that EAT is implicated in the pathophysiologic process of diabetic myocardial disease. In this overview, we will introduce the physiology, pathophysiology of the disease and potential therapeutic strategies, knowledge gaps, and future directions of the role of epicardial adipose tissue in type 2 diabetes mellitus and heart failure to promote the development of novel therapeutic approaches to improve the prognosis of patients with diabetic cardiomyopathy.

Successful Bailout of Noonan Syndrome with Obstructive Hypertrophic Cardiomyopathy During Percutaneous Intramyocardial Septal Radiofrequency Ablation

Background: Cardiac disorders such as hypertrophic cardiomyopathy (HCM) are common in patients with Noonan syndrome (NS). Some patients can develop heart failure associated with HCM, and the long-term outcome of patients with NS with HCM is reported to be worse. Case presentation: We report three patients diagnosed with NS. We initially thought that three patients were diagnosed with only HCM. Three patients' facial features were concealed, making it difficult for us to make a differential diagnosis of NS. Finally, genetic testing identified three patients as NS with HCM. Owing to these patients’ conditions, medical treatment was not effective. Patients were treated with percutaneous intramyocardial septal radiofrequency ablation (PIMSRA). Three patients recovered well, and there was no complication. Conclusions: We describe 3 patients with NS and HCM treated with PIMSRA. PIMSRA is a new therapeutic tool for treating NS with HOCM that can decrease the left ventricular wall thickness, reduce wall stress, and improve cardiac function. Early identification of congenital heart abnormalities and genetic testing are important in diagnosing NS with HCM.