Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide. Over the last two decades, different risk score models, generally assessing the short-term (10-year) risk estimates, have been developed to predict risk and to provide guidance for informed decision-making regarding initiation or intensification of CVD prevention strategies. However, the short-term risk estimation of CVD mortality/morbidity deeply underestimates the lifetime CVD risk, especially in younger age individuals and in women. Moreover, the greatest number of CV events occurs in subjects with low/moderate short-term risk because they are prevalent in the general population. By contrast, estimates of the lifetime risk of CVD may provide a more comprehensive assessment by considering both traditional and non-traditional CV risk factors as well as the potential competing risks, which leads to a more accurate and tailored assessment of the patient's health status. Aim of the present manuscript is to review the latest proposed strategies regarding the estimation of lifetime CV risk and how these strategies may be helpful in daily clinical practice both in primary and secondary prevention.

Heart failure (HF), a life-threatening condition marked by high morbidity and mortality, lacks effective non-pharmacological and minimally invasive treatments. This study presents a novel therapeutic strategy using Airy-beam ultrasound (Airy-US), a non-invasive approach that enables precise cardiac targeting. By employing a 3D-printed ultrasound metasurface, Airy-US generates non-diffractive beams capable of bypassing the ribcage and achieving subwavelength focusing (full width at half maximum, FWHM, 0.8 λ) in deep cardiac tissue. Compared to conventional planar ultrasound (Plane-US), which suffers from waveform distortion and off-target effects, Airy-US preserves focus and reduces unintended impact on surrounding tissue, evidenced by decreased R-R interval variance (3.85 to 2.56 ms). In a doxorubicin (DOX)-induced murine HF model, Airy-US significantly improved cardiac function and reduced myocardial fibrosis without invasive procedures. Moreover, it demonstrated superior biosafety by minimizing arrhythmias. These results highlight the potential of Airy-US as a precise and safe therapeutic modality for HF and possibly other fibrotic diseases. Its ability to focus energy through bone structures opens new opportunities for non-invasive subcostal organ treatments.

Arterial hypertension is the most important modifiable cardiovascular risk factor and a major cause of cardiovascular mortality worldwide. In daily clinical practice, the hypertensive patient is often treated in a uniform way, thus ignoring the significant effects of sex on several aspects of hypertension, including its prevalence, pathophysiology, response to antihypertensive treatment, and outcomes. Along with the immune response and several cardiometabolic risk factors that frequently coexist, the substantial hormonal changes during a woman's life cycle are among the main pathophysiological mechanisms driving hypertension in women. Concurrently, women exhibit increased cardiovascular risk at lower blood pressure (BP) levels compared to age-matched men and present certain disparities in the incidence of cardiovascular events and subsequent hypertension-related cardiovascular prognosis. In addition, women respond differently to antihypertensive treatment, experience more drug-related side effects, and exhibit lower rates of BP control compared to men. Currently, international guidelines propose the same targets and the same therapeutic algorithms for the treatment of hypertension in both sexes without taking into account the sex differences that exist. In this review, we aim to describe certain particularities of arterial hypertension in the female sex, moving from pathophysiological aspects to clinical and therapeutical management.

Hypertension (HTN) is a significant risk factor for heart failure (HF), and both significantly contribute to cardiovascular mortality. This study aims to examine trends and disparities in HF-related mortality among hypertensive older adults (≥65 years) in the United States from 1999 to 2020. Centers for Disease Control and Prevention-Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) database data were analyzed, focusing on HTN as the underlying cause and HF as the contributing cause of death. Age-adjusted mortality rates (AAMRs) and crude rates were stratified by gender, race/ethnicity, age groups, urban-rural status, and geographic regions. The Joinpoint regression program was used to calculate annual percentage changes (APCs) and average annual percentage changes (AAPCs). A total of 259 079 HF-related deaths occurred among hypertensive older adults, with an overall AAMR increase from 11.27 in 1999 to 41.05 in 2020, indicating a clear upward trend (AAPC: 5.51%). Females had higher AAMRs (28.57) than males (25.56); however, males showed a steeper rise in mortality (AAPC: 6.15% vs. 5.23%). Non-Hispanic Blacks had the highest AAMR (43.99), while NH Whites exhibited the most significant increase (AAPC: 5.92%). Mortality rates were highest in the West (AAMR: 34.57) and lowest in the Northeast (21.44). Non-metropolitan areas had a higher AAMR than metropolitan areas (30.69 vs. 26.52). These findings emphasize the necessity for targeted interventions to diminish disparities and tackle increasing mortality rates in vulnerable populations, especially among women, NH Blacks, individuals in the West, and those living in non-metropolitan areas.

Heart failure (HF) is a prevalent and complex clinical syndrome with no single reference standard diagnostic test. Imaging has a supportive role in patients with suspected and known HF, including initial imaging assessment of an adult with suspected HF, but without history of HF, including evaluation of pulmonary edema and detection of left ventricular dysfunction (Variant 1). In adults with established diagnosis of HF but unknown etiology, imaging also has an important role in the assessment of the underlying disease process, including ischemic and nonischemic etiologies (Variant 2). In the course of continuing care for adult patients with an established diagnosis of HF without new symptoms, follow-up imaging is performed to assess for longitudinal changes in ventricular function, response to therapy and prognostication (Variant 3). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical diagnosis with a heterogeneous pathophysiology and clinical presentation. The hallmark of HFpEF is diastolic dysfunction associated with left ventricular remodeling and fibrosis. Myocardial interstitial fibrosis (MIF) occurs as the result of collagen deposition and is dependent on the underlying etiology of heart failure. Detection of MIF can be done by invasive histopathologic sampling or by imaging. More recently, novel biomarkers have been investigated as an alternative tool for not only the detection of MIF but also for the prognostication of patients with HFpEF which may in turn alleviate the need for invasive and expensive imaging in the future.

Experimental studies have reported that Factor Xa inhibitors (Xa-Is) have positive effects on cardiac muscles and blood vessels via protease-activated receptor 2 inhibition, suggesting the preventive effects of Xa-Is on cardiovascular events. However, the clinical impact of Xa-Is on cardiovascular disease is unknown.

This study aimed to investigate the incidence of cardiovascular events among older patients with nonvalvular atrial fibrillation (NVAF) taking Xa-Is compared with those taking non-Xa-Is.

We conducted a single-center historical cohort study of consecutive patients with NVAF who were aged ≥80 years and used oral anticoagulants. Xa-Is included rivaroxaban, apixaban, and edoxaban, and non-Xa-Is included dabigatran and warfarin. The outcome of cardiovascular events was defined as a composite outcome of congestive heart failure, arteriosclerotic disease, and cardiovascular death. We compared the 5-year incidence of cardiovascular events between patients taking Xa-Is and those taking non-Xa-Is.

Of 1705 patients aged ≥80 years who were diagnosed with AF, 1092 patients with NVAF were enrolled. Propensity score matching provided 445 patients in each group. The risks of cardiovascular events, congestive heart failure, arteriosclerotic disease, and cardiovascular death were significantly lower in the Xa-I group than in the non-Xa-I group (hazard ratio [95% confidence interval]: 0.43 [0.30-0.61], 0.44 [0.29-0.66], 0.47 [0.22-1.04], and 0.41 [0.23-0.75], respectively).

Among patients with NVAF who were aged ≥80 years, the incidence of cardiovascular events was lower in the Xa-I users than in the non-Xa-I users.

Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection techniques. Herein, a unique hydrogel incorporating extracellular matrix from fish swim bladder (FSB-ECM), which has distinct advantages over mammalian derived ECM, such as low antigenicity, bioactivity, and source safety, is developed. It consists of collagen, glycoproteins, and proteoglycans, including 13 proteins common in the myocardial matrix and three specific proteins: HSPG, Col12a1, and vWF. This hydrogel enhances cardiac cell adhesion and stretching while promoting angiogenesis and M2 macrophage polarization. In addition, its storage modulus (G') increases over time, reaching about 1000 Pa after 5 min, which facilitates transcatheter delivery and in situ gelling. Furthermore, this hydrogel provides sustained support for cardiac contractions, exhibiting superior longevity. In a rat model of ischemic heart failure, the ejection fraction significantly improves with FSB-ECM treatment, accompanied by increased angiogenesis, reduced inflammation, and decreased infarct size. Finally, RNA sequencing combined with in vitro assays identifies ANGPTL4 as a key protein involved in mediating the effects of FSB-ECM treatment. Overall, this new injectable hydrogel based on FSB-ECM is suitable for transcatheter delivery and possesses remarkable reparative capabilities for treating heart failure.

Coronary artery disease (CAD) is a leading etiology of heart failure (HF) and serves as a significant therapeutic target to ameliorate HF-associated morbidity and mortality. Key management considerations include pharmacologic treatment, electrophysiological devices, and coronary revascularization, aimed toward preventing CAD progression, left ventricular remodeling, sudden death, and reinfarction. The optimal revascularization strategy for patients with CAD and HF who are surgical candidates requires careful assessment of each patients' unique risk/benefit profile and individual preferences. Several novel pharmacologic agents are in development with hopes of adding to the armamentarium of treatment of CAD and HF.

Implantable cardioverter defibrillators (ICDs) reliably prevent death due to life-threatening arrhythmias; this may become less relevant in people with more severe heart failure who are reaching the end of life (EOL). This review aimed to explore the ICD deactivation process and identify ethical issues, especially around the initiation of relevant discussions among professionals and patients. Available literature was reviewed using four electronic databases to identify issues that may deter healthcare professionals from having important deactivation discussions and to address considerations for ICD management prior to the EOL. The search resulted in the retainment of 12 studies. Three themes emerged from the data: barriers and facilitators, ethical considerations in clinical practice, and nurse's role. Lack of knowledge, which has been associated with cultural differences, has been found among the barriers, and interdisciplinary education and open communication appeared as facilitators. As clinicians' ethical considerations and fears emerged from the literature, nurses' special role has not been sufficiently supported. Complex care requires facilitation by multidisciplinary teams and education around the device's function regarding EOL issues. Establishing expert consensus statements on advance care planning might help define the distinct roles of each healthcare practitioner involved. Further research is needed in addressing the identified gaps.

Five risk factors account for approximately 50% of the global burden of cardiovascular disease. How the presence or absence of classic risk factors affects lifetime estimates of cardiovascular disease and death from any cause remains unclear.

We harmonized individual-level data from 2,078,948 participants across 133 cohorts, 39 countries, and 6 continents. Lifetime risk of cardiovascular disease and death from any cause was estimated up to 90 years of age according to the presence or absence of arterial hypertension, hyperlipidemia, underweight and overweight or obesity, diabetes, and smoking at 50 years of age. Differences in life span (in terms of additional life-years free of cardiovascular disease or death from any cause) according to the presence or absence of these risk factors were also estimated. Risk-factor trajectories were analyzed to predict lifetime differences according to risk-factor variation.

The lifetime risk of cardiovascular disease was 24% (95% confidence interval [CI], 21 to 30) among women and 38% (95% CI, 30 to 45) among men for whom all five risk factors were present. In the comparison between participants with none of the risk factors and those with all the risk factors, the estimated number of additional life-years free of cardiovascular disease was 13.3 (95% CI, 11.2 to 15.7) for women and 10.6 (95% CI, 9.2 to 12.9) for men; the estimated number of additional life-years free of death was 14.5 (95% CI, 9.1 to 15.3) for women and 11.8 (95% CI, 10.1 to 13.6) for men. As compared with no changes in the presence of all risk factors, modification of hypertension at an age of 55 to less than 60 years was associated with the most additional life-years free of cardiovascular disease, and modification of smoking at an age of 55 to less than 60 years was associated with the most additional life-years free of death.

The absence of five classic risk factors at 50 years of age was associated with more than a decade greater life expectancy than the presence of all five risk factors, in both sexes. Persons who modified hypertension and smoking in midlife had the most additional life-years free of cardiovascular disease and death from any cause, respectively. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov number, NCT05466825.).

Atrial fibrillation (AF) is one of the most prevalent cardiac arrhythmias in the world. Patients with AF also suffer from heart failure (HF). The relationship between AF and HF is often considered bidirectional and both share very similar risk factors. The mechanism of AF-induced cardiomyopathy lies in 3 distinct components: tachycardia-related cardiac dysfunction, heart rhythm irregularity, and AF-induced atrial myopathy. These components are mediated by calcium mishandling, neurohormonal activation, oxidative stress, myocardial supply-demand mismatch, and irreversible fibrosis and remodeling. Managing AF-induced cardiomyopathy should focus on early rhythm control to mitigate the development of irreversible remodeling and atrial myopathy.

Atrial fibrillation and heart failure are common cardiovascular conditions that are intricately linked to each other, with a significant impact on morbidity, mortality, and quality of life. These two conditions can create a vicious pathophysiologic milieu associated with neurohormonal changes, elevated cardiac filling pressure, myocardial remodeling, systemic and regional inflammation, fibrosis, and diminished myocardial contractility. It is well known that cardiomyopathy can cause atrial fibrillation and vice-versa, but often it is difficult to sort which came first. Unfortunately, the disease burden will only continue to rise with an aging population, and understanding the epidemiology of the disease and the interplay of these two conditions is vital to improved patient care.

Heart failure (HF) is a common complication of ST-elevation myocardial infarction (STEMI) in low- and middle-income countries (LMICs), where cardiovascular mortality is disproportionately high. Primary percutaneous coronary intervention (PCI) has reduced post-STEMI HF incidence in high-income countries. However, access to this standard of care is poor in LMICs, and data in these settings remain scarce.

To identify predictors of HF following STEMI in a LMIC with limited access to PCI, aiming at better management and outcomes.

This retrospective cohort study analyzed 2,467 STEMI patients admitted to two Brazilian public hospitals between January/2015 and February/2020. All participants received pharmacological thrombolysis and underwent coronarography within 48h post-admission. The primary outcome was symptomatic HF, defined as dyspnea with chest X-ray evidence of congestion, from 48h post-admission until discharge. Stepwise binary logistic regression was used to identify HF predictors. Significance was defined as p-values<0.05.

The population was 61.9% male, mean age was 58.3±12.6 years, and 39.9% developed post-STEMI HF. HF was more common among older men with cardiovascular-kidney-metabolic (CKM) disease, larger infarcts, and left anterior descending artery involvement. Medications were often underprescribed at discharge, especially aldosterone antagonists (11.0%). HF was notably more frequent among individuals with failed thrombolysis (47.0%).

This regionally representative cohort from a LMIC with limited access to PCI showed that older men with CKM disease are particularly vulnerable to post-STEMI HF, and that HF pharmacotherapy at discharge needs optimization. The high HF incidence among patients with failed thrombolysis highlights the need to expand PCI availability.

Heart failure (HF) is one of the most common cardiovascular disorders, and its prevalence is increased due to age, genetics, and lifestyle factors. Emerging evidence suggests that the Mediterranean Diet (Med Diet) is linked to lower all-cause mortality in patients with increased cardiovascular disease risk, such as those with HF.

To conduct a systematic review and meta-analysis of observational studies into the relationship between the Med Diet on HF risk.

Several databases (PubMed, Scopus, Web of Science and Cochrane Library) until the 01st of May 2023 were searched. Our research was conducted based on the updated 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were reported as risk ratios (RRs) with their 95% confidence intervals (CIs) as results of multivariate or univariate analyses.

From the original 1206 studies collected, six observational prospective studies were included, with a total of 216,385 European participants without evidence of HF at baseline. Over a mean period of 11 years of follow-up, a 1-point increase in the Med Diet score was associated with a significantly lower risk of HF (RR = 0.940; 95% CI: 0.912-0.969, p < 0.0001; I2 = 42.9%). Categorised by sex, a higher adherence to Med Diet was associated with a significantly lower incidence of HF in women (RR = 0.942; 95% CI: 0.912-0.973, p = 0.001; I2 = 41.8%), but not in men. The overall quality of included studies was good.

Higher adherence to Med Diet across European countries is associated with lower risk of HF, particularly in women.

Coronary Computed Tomography Angiography (CCTA) is commonly used to identify coronary artery disease. In this study, the indications for CCTA referrals are reviewed, to identify the strongest predictors of CAD, as seen on CCTA. A retrospective study, reviewing the electronic health records of consecutive patients who underwent CCTA between July and November 2020 at our Trust, was conducted. A total of 485 patient reports were reviewed. Of patients with moderate-to-severe CAD, 128 (73.6%) were hypertensive. Of those with severe CAD, 79 patients (76%) were hypertensive. Univariate analysis for comparison of patients with absent (n = 219), mild (n = 92), moderate (n = 70) and severe (n = 104) CAD revealed that hypertension (P < .001), diabetes mellitus (P < .001), gender (P < .001), dyslipidemia (P < .001) and smoking (P = .006), were each significantly associated with the presence of CAD on CCTA. However, multiple logistic regression analysis confirmed that hypertension has the strongest association with CAD (OR = 2.22, P < .001) Furthermore, the presence of typical chest pain in hypertensive patients was strongly associated with significant CAD, on CCTA. Among all risk factors, hypertension is the strongest independent predictor for the presence of CAD on CCTA. These results suggest that hypertension is a significant factor when considering referral for CCTA, particularly when associated with chest pain.

Heart failure with preserved ejection fraction (HFpEF) is associated with elevated rates of readmission and mortality. Accurate prediction of readmission risk is essential for optimizing healthcare resources and enhancing patient outcomes.

We conducted a retrospective cohort study utilizing HFpEF patient data from two institutions: the First Affiliated Hospital Zhejiang University School of Medicine for model development and internal validation, and the Affiliated Hospital of Xuzhou Medical University for external validation. A machine learning (ML) model was developed and validated using 53 variables to predict the risk of readmission within one year. The model's performance was assessed using several metrics, including the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, F1 score, model training time, model prediction time and brier score. SHAP (SHapley Additive exPlanations) analysis was employed to enhance model interpretability, and a dynamic nomogram was constructed to visualize the predictive model.

Among the 766 HFpEF patients included in the study, 203 (26.5%) were readmitted within one year. The LightGBM model exhibited the highest predictive performance, with an AUC of 0.88 (95% confidence interval (CI):0.84-0.91), an accuracy of 0.79, a sensitivity of 0.81, and a specificity of 0.78. Key predictors included the E/e' ratio, NYHA classification, LVEF, age, BNP levels, MLR, history of atrial fibrillation (AF), use of ACEI/ARB/ARNI, and history of myocardial infarction (MI). External validation also demonstrated strong predictive performance, with an AUC of 0.87 (95%CI:0.83-0.91).

The LightGBM model exhibited robust performance in predicting one-year readmission risk among HFpEF patients, providing a valuable tool for clinicians to identify high-risk individuals and implement timely interventions.

Background: The study investigates age-related differences in the prevalence and extent of coronary artery disease (CAD), as well as long-term outcomes in a large cohort of unselected patients undergoing invasive coronary angiography (CA). The aging population, along with an increasing number of older and multi-morbid patients undergoing CA, poses challenges for healthcare systems. Despite this, studies investigating age-related differences in the long-term outcomes of unselected patients undergoing CA are limited. Methods: Consecutive patients undergoing invasive CA from 2016 to 2022 were included from one institution. The prognosis of patients undergoing CA stratified by pre-specified age groups (i.e., 40-<60, 60-<80 and ≥80 years) was investigated with regard to the primary endpoint of rehospitalization for heart failure (HF), as well as the risks of acute myocardial infarction (AMI) and coronary revascularization at 36 months. Results: From 2016 to 2022, 7520 patients undergoing CA were included with a median age of 70 years (mean: 69 years). The prevalence of CAD (61.9% vs. 71.8% vs. 77.3%; p = 0.001), as well as the prevalence of three-vessel CAD (21.0% vs. 31.5% vs. 36.1%) increased with age. At 36 months, patients ≥ 80 years of age had the highest rates of rehospitalization for HF, followed by patients 60-<80 years and patients 40-<60 years (28.4% vs. 23.2% vs. 14.0%; p = 0.001). Consequently, compared to younger patients (i.e., 40-<60 years of age), those ≥80 years of age exhibited the highest risk of HF-related rehospitalization (≥ 80 years: HR = 2.205; 95% CI 1.884-2.579; p = 0.001), followed by those 60-< 80 years (HR = 1.765; 95% CI 1.536-2.029; p = 0.001). The increased risk of rehospitalization for HF at 36 months was still observed after multivariable adjustment (i.e., ≥80 years: HR = 1.265; 95% CI 1.049-1.524; p = 0.014; 60-<80 years: HR = 1.339; 95% CI 1.145-1.565; p = 0.001) and was specifically evident in patients with left ventricular ejection fraction ≥ 35% and in patients without evidence of CAD/single-vessel CAD. In contrast, the rates of AMI and coronary revascularization at 36 months did not differ significantly among different age groups. Conclusions: Advanced age is an independent predictor of rehospitalization for HF in patients undergoing CA, but not AMI and revascularization during long-term follow-up. This highlights the importance of optimizing diagnostic and therapeutic strategies for HF, particularly in older patients undergoing CA.

The study investigates the prognostic impact of sex and sex-related differences in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). More data regarding the characterization of patients and their outcomes in the presence of HFmrEF are needed.

Consecutive patients hospitalized with HFmrEF (ie, left ventricular ejection fraction 41%-49% and signs or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Female patients were compared with male patients with regard to the primary end point of all-cause mortality at 30 months (median follow-up). Statistical analyses comprised Kaplan-Meier, multivariable Cox proportional regression analyses and propensity score matching. From a total of 2184 patients hospitalized with HFmrEF, 64.6% were male. Female patients with HFmrEF were older than male patients (median age 78 versus 73 years; P=0.001) and had lower rates of ischemic cardiomyopathy (46.6% versus 63.6%; P=0.001). Within the entire study cohort, sex was not associated with the risk of all-cause mortality (hazard ratio [HR], 0.931 [95% CI, 0.797-1.088]; P=0.372). However, male sex was associated with a lower risk of HF-related rehospitalization at 30 months (HR, 0.761 [95% CI, 0.600-0.966]; P=0.026), which was confirmed after multivariable adjustment (HR, 0.759 [95% CI, 0.592-0.973]; P=0.029) and propensity score matching (HR, 0.722 [95% CI, 0.539-0.967]; P=0.029).

Although almost two thirds of patients hospitalized with HFmrEF were male, sex was no predictor for the risk of all-cause mortality at 30 months. However, female sex was associated with a higher risk of HF-related rehospitalization.

URL: https://clinicaltrials.gov; Unique identifier: NCT05603390.

Background: The study investigates sex-related differences and outcomes in unselected patients undergoing invasive coronary angiography (CA). Sex-based differences with regard to baseline characteristics and management of patients with cardiovascular disease have yet been demonstrated. However, their impact on long-term outcomes in unselected patients undergoing CA remains unknown. Methods: Consecutive patients undergoing invasive CA from 2016 to 2022 were included at one institution. Prognosis of male and female patients undergoing CA was investigated with regard to the primary endpoint of rehospitalization for heart failure (HF) at 36 months. Secondary endpoints comprised the risk of acute myocardial infarction (AMI) and coronary revascularization at 36 months, as well as in-hospital all-cause mortality. Statistical analyses included Kaplan-Meier analyses, as well as uni- and multivariable Cox proportional regression analyses. Results: From 2016 to 2022, 7691 patients undergoing CA were included (males: 65.1%; females: 34.9%). Males had a higher prevalence of coronary artery disease (CAD) (76.2% vs. 57.4%; p = 0.001), alongside a higher prevalence of 3-vessel CAD compared to females (33.9% vs. 20.3%; p = 0.001). The risk of rehospitalization for HF at 36 months was higher in males compared to females (22.4% vs. 20.3%; p = 0.036; HR = 1.127; 95% CI: 1.014-1.254; p = 0.027), which was no longer observed after multivariable adjustment. Male sex was associated with a higher risk of coronary revascularization (9.6% vs. 5.9%; p = 0.001; HR = 1.659; 95% CI: 1.379-1.997; p = 0.001), which was still evident after multivariable adjustment (HR = 1.650; 95% CI 1.341-2.029; p = 0.001). However, neither the risk of AMI at 36 months (8.1% vs. 6.9%; p = 0.077), nor the risk of in-hospital all-cause mortality (6.9% vs. 6.5%; p = 0.689) differed significantly between the two sexes. Conclusions: In consecutive patients undergoing coronary angiography, male sex was independently associated with an increased risk of coronary revascularization, but not HF-related rehospitalization.

The aim of this study was to implement a model of healthcare for patients with heart failure (HF) and to assess the differences between men and women in the study population.

Through care and an extensive educational panel (dietary recommendations, physical activity, titration of diuretics, psychological support), emphasis was placed on prevention. All patients had a baseline cardiology consultation with recommendations regarding treatment, self-care, diet, and exercise. Based on regular measurements of weight and blood pressure HF patients were telemonitored by nurses, primary care physicians and referred to cardiologists when necessary. The questionnaire was conducted in all patients at baseline after enrollment to the study and after 3 months of telemonitoring and extensive educational process.

The study finally included 140 men with an average age of 66 years (SD: 56-71) and 163 women with an average age of 64 years (58-72). The ischemic origin of HF was present in 78% of men and 73% of women (p = 0.40), and 31% of men and 16% of women declared myocardial infarction in the past (p = 0.002). Men more often survived sudden cardiac arrest (7.8% vs. 1.2%; p = 0.004) and had implantable cardiac devices compared to women (16% vs. 3%; p = 0.001). Male patients reported significantly more often alcohol consumption, smoking, and less frequently any physical activity. Women significantly more often than men suffered from cancer, depression, and thromboembolic events and less frequently from obstructive sleep apnea. The mean left ventricular ejection fraction (LVEF) was 43% (SD: 30-58) for men, and 57% (45-63) for women (p = 0.0001), and women suffered mainly from heart failure with preserved ejection fraction. There were no differences between genders regarding the number of hospitalizations in last 12 months. The men, despite lower LVEF, felt short of breath/tired when climbing the stairs up than women (3 [2-4] vs. 2 floors [1-3]; p = 0.001), had higher distance in meters when walking on flat ground (400 [200-400] vs. 300 m [100-400]; p = 0.0001), and less frequently had to get up to go to the toilet at night (p = 0.03). Men also suffered significantly less often from shortness of breath at rest, swelling of the lower limbs and shortness of breath that wakes them up at night. Only 35% of men and 19% of women had HF self-care training, and only 35% of men and 46% of women knew how to increase the dose of diuretic on their own if shortness of breath or swelling increases. Based on the EuroQol-5 dimensions 5-levels questionnaire, significantly more women than men reported moderate and serious problems with moving around, serious problems with performing ordinary activities independently as well as moderate and serious pain problem and a significant level of anxiety. Men more often than women reported serious problems with self-care.

Women suffer more often from HF symptoms and have worse quality of life assessed in EQ-5D-5L than men despite their higher LVEF.

This review focuses on the sex-related differences of patients in etiological factors, clinical picture, and objective laboratory and instrumental signs of heart failure. The authors performed an analysis of the effectiveness of drug and non-drug treatments depending on the gender of patients with low and preserved left ventricular ejection fraction, which should improve the quality of medical care and outcomes in patients with heart failure.

Background and Objectives: Heart failure is associated with high morbidity and mortality and linked with several pre-existing health conditions and risk factors. Early detection and prompt management in heart failure improves patient outcomes. Liver involvement is associated with heart failure disease progression, and hence liver biomarkers and liver fibrosis may have a prognostic impact. Several blood test based markers and scoring systems estimate liver fibrosis and hence can be useful prognostic tools. Materials and Methods: We retrospectively analyzed a series of 303 patients with decompensated heart failure in a city in western Romania over a period of 6 months. Several biochemical parameters were measured, the FIB-4 score was estimated and echocardiography was performed. Results for targeted variables are presented using descriptive statistics. Patients were analyzed based on their LVEF categories. Statistical analysis was based on ANOVA one-way tests for continuous variables and Chi-square tests for categorical variables. Pairwise comparisons were performed based on Bonferroni adjusted significance tests. The correlations between FIB-4 score, LVEF and NT-pro BNP in patients with and without diabetes and hypertension were explored using Spearman's correlation coefficient. Result: Age, gender, NYHA class, death, history of (h/o) type 2 diabetes mellitus (T2DM), h/o coronary artery disease (CAD), h/o arrhythmias, sodium, potassium, creatinine, eGFR, uric acid, NT-pro BNP, left atrial volume, LDL, HDL, and TG were analyzed by LVEF categories using ANOVA one-way tests, Chi-square tests, and Bonferroni correction comparisons. We found a strong statistically significant correlation between each of NT-pro BNP, left atrial volume, LDL, and HDL with the LVEF categories. Discussion: Early detection of cardiac dysfunction leads to better management in patients with cardiovascular risk factors including diabetes and hypertension. High LDL and low HDL levels contribute to a reduction in left ventricular (LV) function. Available literature suggests the FIB-4 score as superior to other non-invasive markers of fibrosis. It utilizes the patient's age, platelet count, AST, and ALT, which can be available retrospectively, making it an easy and inexpensive tool. FIB-4 score has a few limitations. Conclusions: Our study has shown a statistically significant positive correlation between severity categories of LVEF and FIB-4 score for heart failure patients with and without diabetes, and for heart failure patients with or without hypertension. We propose the implementation of FIB-4 score as a prognostic tool for heart failure.

Biological sex influences the risk of depression and cognitive impairment, but its role in relation to postoperative delirium is unclear. This analysis investigates sex differences in delirium risk after coronary artery bypass graft (CABG) surgery and sex-related differences in relation to affective and cognitive symptoms.

This is a secondary analysis of the Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study, a single-site, observational study of a CABG surgery cohort (n = 149). Preoperative characteristics are stratified by sex, and baseline variables that differ by sex are evaluated to understand whether sex modifies their relationships with delirium. We also evaluate sex differences in one-month depression and cognition.

Female sex is associated with several delirium risk factors, including higher risk of preoperative depression and middle cerebral artery (MCA) stenosis. MCA stenosis was statistically associated with delirium only among women (OR 15.6, 95% CI 1.5, 164.4); mild cognitive impairment (MCI) was associated with delirium only in men (OR 4.6, 95% CI 1.2, 17.9). Other sex-based differences failed to reach statistical significance. Depression remained commoner among women 1 month post-CABG.

Women in this CABG cohort were more likely to have depression at baseline and 1 month postoperatively, as well as MCA stenosis and postoperative delirium. Sex might modify the relationship between post-CABG delirium and its risk factors including MCA stenosis and MCI. Cerebrovascular disease deserves study as a potential explanation linking female sex and a range of poor outcomes among women with coronary heart disease.

Acute heart failure (AHF) is a major cause of hospitalizations and death in the elderly. However, elderly patients are often underrepresented in randomized clinical trials. We analysed the impact of age on clinical outcomes and response to treatment in patients enrolled in Relaxin in Acute Heart Failure (RELAX-AHF-2), a study that included older patients than in previous AHF trials.

The RELAX-AHF-2 randomized patients admitted for AHF to infusion of serelaxin or placebo. We examined the association of pre-specified clinical outcomes and treatment effect according to age categories [(years): <65 (n = 1411), 65-74 (n = 1832), 75-79 (n = 1222), 80-84 (n = 1156) and ≥85 (n = 924)]. The mean age of the 6545 patients enrolled in RELAX-AHF-2 was 73.0 ± 11 years. The risk of all-cause and cardiovascular (CV) death (all p < 0.001) as well as the composite endpoint of CV death or heart failure/renal failure rehospitalization through 180 days (p = 0.002) and hospital discharge through day 60 (p = 0.013) were all directly associated with age categories. Age remained independently associated with outcomes after adjustment for clinical confounders and the results were consistent when age was analysed continuously. No clinically significant change in treatment effects of serelaxin was observed across age categories for the pre-specified endpoints (interaction p > 0.05).

Elderly patients are at higher risk of short- and long-term CV outcomes after a hospitalization for AHF. Further efforts are needed to improve CV outcomes in this population.

Cardiovascular disease (CVD) is a leading cause of death worldwide, and the number of patients with CVD continues to increase despite extensive research and developments in this field. Chronic inflammation is a pivotal pathological component of CVD, and unveiling new proinflammatory factors will help devise novel preventive and therapeutic strategies. The extracellular matrix (ECM) not only provides structural support between cells but also contributes to cellular functions. Secreted protein acidic and rich in cysteine (SPARC) is a collagen-binding matricellular protein that is particularly induced during development and tissue remodeling. A proinflammatory role for SPARC has been demonstrated in various animal models, such as in the lipopolysaccharide-induced footpad model and dextran sodium sulfate-induced colitis model. Recent clinical studies reported a positive correlation between elevated plasma SPARC levels and hypertension, obesity, and the inflammatory marker high-sensitive C-reactive protein. In addition, SPARC gene deletion attenuates the cardiac injury induced by aging, myocardial infarction, and pressure load, suggesting that SPARC has deleterious effects on CVD. This review summarizes the regulatory and proinflammatory mechanisms of SPARC on CVD, chronic kidney disease (CKD), and cerebrovascular disease and discusses the rationale behind measuring SPARC as a biomarker of CVD and the effects of inhibition of SPARC in the prevention and treatment of CVD.

Sex differences in long-term post-discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world-wide implementation of guideline-directed medical therapy for decades. The present study aims to elucidate the puzzling dilemma and to depict the directions of solution.

Between 2011 and 2020, a total of 12 428 patients (6518 men and 5910 women, mean age 73.50 ± 14.85) hospitalized for acute decompensated HF were retrospectively enrolled from a university HF cohort. Compared with men, women hospitalized for acute decompensated HF were older in age (76.40 ± 13.43 vs. 71.20 ± 15.67 years old, P < 0.0001) with more coexisting hypertension, diabetes, hyperlipidaemia and moderate to severe chronic kidney disease, but less with ischaemic heart disease, cerebrovascular disease and chronic obstructive pulmonary disease (P < 0.0001). In echocardiography measurement parameters, women had smaller left ventricular and left atrial dimensions, higher left ventricular mass index, higher left ventricular ejection fraction (LVEF) and more in HF with preserved ejection fraction (EF) category (LVEF > 50%) than men (P < 0.0001). In HF therapy, women compared with men received more guideline-directed medical HF therapies including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors, but similar beta-blockers and mineralocorticoid receptor antagonists (P < 0.0001). Post-discharge long-term clinical outcomes after multivariate-adjusted analysis revealed that women compared with men had lower all-cause mortality [adjusted hazard ratio (aHR): 0.89, 95% confidence interval (CI): 0.84-0.93], lower cardiovascular mortality (aHR: 0.89, 95% CI: 0.80-0.99) and lower 1 year mortality (aHR: 0.91, 95% CI: 0.84-0.99) but similar HF rehospitalization rate (aHR: 1.02, 95% CI: 0.95-1.09) over 8 years of follow-up. The superiority of women over men in all-cause mortality was shown in HF with preserved EF (>50%) and HF with mildly reduced EF (40%-50%), but not in HF with reduced EF (<40%) category. Subgroup forest plot analysis showed body mass index, coexisting hypertension and chronic obstructive pulmonary disease as significant interacting factors.

With more coronary risk factors and medical comorbidities, less cardiac remodelling and better adherence to guideline-directed HF therapy, women hospitalized for acute decompensated HF demonstrated superiority over men in long-term post-discharge clinical outcomes, including all-cause mortality, cardiovascular mortality and 1 year mortality, and mainly in HF with preserved and mid-range EF categories, in the Asian HF cohort.

Cardiac time intervals are sensitive markers of myocardial dysfunction that predispose to heart failure (HF). We aimed to investigate the association between cardiac time intervals and HF in patients with acute coronary syndrome (ACS).

This study included 386 ACS patients treated with percutaneous coronary intervention (PCI). Patients underwent an echocardiography examination a median of two days after PCI. Cardiac time intervals including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and systolic ejection time (ET), and myocardial performance index (MPI) were obtained by tissue Doppler echocardiography. The outcome was incident HF.

During follow-up (median 4.3, IQR:1.0-6.7 years), 140 (36%) developed HF. In unadjusted analyses, IVRT was not associated with HF (HR 1.02 (0.95-1.10), p = 0.61, per 10ms increase), and neither was IVCT (HR 0.07 (0.95-1.22), p = 0.26, per 10ms increase). Increasing MPI was associated with a higher risk of HF (HR 1.20 (1.08-1.34), P = 0.001, per 0.1 increase), and so was decreasing ET (HR 1.13 (1.07-1.18), P < 0.001 per 10ms decrease). After multivariable adjustment for cardiovascular risk factors, MPI (HR 1.13 (1.01-1.27), P = 0.034) and ET (HR 1.09 (1.01-1.17), P = 0.025) remained significantly associated with incident HF. LVEF modified the association between ET and HF (p for interaction = 0.002), such that ET was associated with HF in patients with LVEF ≥ 36% (HR = 1.15 (1.06-1.24), P = 0.001, per 10ms decrease).

In patients admitted with ACS, shortened ET and higher MPI were independently associated with an increased risk of incident HF. Additionally, ET was associated with incident HF in patients with LVEF above 36%.

Sex characteristics exhibit significant disparities in various human diseases, including prevalent cardiovascular diseases, cancers, metabolic disorders, autoimmune diseases, and neurodegenerative diseases. Risk profiles and pathological manifestations of these diseases exhibit notable variations between sexes. The underlying reasons for these sex disparities encompass multifactorial elements, such as physiology, genetics, and environment. Recent studies have shown that human body systems demonstrate sex-specific gene expression during critical developmental stages and gene editing processes. These genes, differentially expressed based on different sex, may be regulated by androgen or estrogen-responsive elements, thereby influencing the incidence and presentation of cardiovascular, oncological, metabolic, immune, and neurological diseases across sexes. However, despite the existence of sex differences in patients with human diseases, treatment guidelines predominantly rely on male data due to the underrepresentation of women in clinical trials. At present, there exists a substantial knowledge gap concerning sex-specific mechanisms and clinical treatments for diverse diseases. Therefore, this review aims to elucidate the advances of sex differences on human diseases by examining epidemiological factors, pathogenesis, and innovative progress of clinical treatments in accordance with the distinctive risk characteristics of each disease and provide a new theoretical and practical basis for further optimizing individualized treatment and improving patient prognosis.

This study aimed to investigate the role of sex in the association between physical function and the occurrence of hospitalization and mortality among community-dwelling older adults with impairments in activities of daily living (ADL). Participants included community-dwelling older adults aged ≥65 years with ADL disabilities. Physical functions (hand grip strength [HGS], knee extension muscle strength, and comfortable walking speed [CWS]) were measured at baseline and analyzed for association with hospitalization and mortality by sex using Cox regression analysis, adjusted for potential confounders. In this Cox regression analysis, HGS was significantly associated with the occurrence of hospitalization and mortality in women, whereas CWS was significantly associated with the occurrence of hospitalization and HGS with mortality in men. These findings reveal that the predictive ability of adverse events in community-dwelling older adults with disabilities differs by sex, requiring outcome- and sex-specific prognostication.

Objective.Instantaneous, non-invasive evaluation of left ventricular end-diastolic pressure (LVEDP) would have significant value in the diagnosis and treatment of heart failure. A new approach called cardiac triangle mapping (CTM) has been recently proposed, which can provide a non-invasive estimate of LVEDP. We hypothesized that a hybrid machine-learning (ML) method based on CTM can instantaneously identify an elevated LVEDP using simultaneously measured femoral pressure waveform and electrocardiogram (ECG).Approach.We studied 46 patients (Age: 39-90 (66.4 ± 9.9), BMI: 20.2-36.8 (27.6 ± 4.1), 12 females) scheduled for clinical left heart catheterizations or coronary angiograms at University of Southern California Keck Medical Center. Exclusion criteria included severe mitral/aortic valve disease; severe carotid stenosis; aortic abnormalities; ventricular paced rhythm; left bundle branch and anterior fascicular blocks; interventricular conduction delay; and atrial fibrillation. Invasive LVEDP and pressure waveforms at the iliac bifurcation were measured using transducer-tipped Millar catheters with simultaneous ECG. LVEDP range was 9.3-40.5 mmHg. LVEDP = 18 mmHg was used as cutoff. Random forest (RF) classifiers were trained using data from 36 patients and blindly tested on 10 patients.Main results.Our proposed ML classifier models accurately predict true LVEDP classes using appropriate physics-based features, where the most accurate demonstrates 100.0% (elevated) and 80.0% (normal) success in predicting true LVEDP classes on blind data.Significance.We demonstrated that physics-based ML models can instantaneously classify LVEDP using information from femoral waveforms and ECGs. Although an invasive validation, the required ML inputs can be potentially obtained non-invasively.

This study aimed to examine the diagnostic pathways and outcomes of patients with heart failure (HF), stratified by left ventricular ejection fraction (EF), and to highlight deficiencies in real-world HF diagnosis and management.

We conducted a retrospective cohort study in Salford, United Kingdom, utilizing linked primary and secondary care data for HF patients diagnosed between January 2010 and November 2019. We evaluated characteristics, diagnostic patterns, healthcare resource utilization, and outcomes. Patients were categorized according to baseline (the latest measure prior to or within 90 days post-diagnosis) as having HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF), or preserved EF (HFpEF). The data encompassed a 2 year period before diagnosis and up to 5 years post-diagnosis. A total of 3227 patients were diagnosed with HF between January 2010 and November 2019. The mean follow-up time was 2.6 [±1.9 standard deviation (SD)] years. The mean age at diagnosis was 74.8 (±12.7 SD) years, and 1469 (45.5%) were female. HFpEF was the largest cohort (46.6%, npEF = 1505), HFmrEF constituted 16.1% (nmrEF = 520), and HFrEF 18.5% (nrEF = 596) of the population, while 18.8% (nu = 606) of patients remained unassigned due to insufficient evidence to support categorization. At baseline, measurement of natriuretic peptide (NP; brain NP and N-terminal pro-B-type NP) and echocardiographic report data were available for 592 (18.3%) and 2621 (81.2%) patients, respectively. A total of 2099 (65.0%) of the HF cohort had access to a cardiology-led outpatient clinic prior to the HF diagnosis, and 602 (18.7%) attended cardiac rehabilitation post-diagnosis. The 5 year crude survival rate was 37.8% [95% confidence interval (CI) (35.2-40.7%)], 42.3% [95% CI (38.0-47.2%)], and 45.5% [95% CI (41.0-50.4%)] for HFpEF, HFrEF, and HFmrEF, respectively.

Low survival rates were observed across all HF groups, along with suboptimal rates of NP testing and specialist assessments. These findings suggest missed opportunities for timely and accurate HF diagnosis, a pivotal first step in improving outcomes for HF patients. Addressing these gaps in diagnosis and management is urgently needed.

In this study, we explored the role of apoptosis as a potential biomarker for cardiac failure using functional micro-CT and fluorescence molecular tomography (FMT) imaging techniques in Ercc1 mutant mice. Ercc1 is involved in multiple DNA repair pathways, and its mutations contribute to accelerated aging phenotypes in both humans and mice, due to the accumulation of DNA lesions that impair vital DNA functions. We previously found that systemic mutations and cardiomyocyte-restricted deletion of Ercc1 in mice results in left ventricular (LV) dysfunction at older age.

Here we report that combined functional micro-CT and FMT imaging allowed us to detect apoptosis in systemic Ercc1 mutant mice prior to the development of overt LV dysfunction, suggesting its potential as an early indicator and contributing factor of cardiac impairment. The detection of apoptosis in vivo was feasible as early as 12 weeks of age, even when global LV function appeared normal, underscoring the potential of apoptosis as an early predictor of LV dysfunction, which subsequently manifested at 24 weeks.

This study highlights the utility of combined functional micro-CT and FMT imaging in assessing cardiac function and detecting apoptosis, providing valuable insights into the potential of apoptosis as an early biomarker for cardiac failure.