Risk Of Cardiovascular Death Research Articles

Myocardial dysfunction in patients with rheumatoid arthritis in the speckle-tracking echocardiography and its relationship with the clinical characteristics of the disease

patients with RA have an approximately 50% increased risk of cardiovascular events and cardiovascular death. Cardiovascular diseases lead to a decrease in life expectancy, and the determination of the mechanisms of myocardial damage in patients with RA is of great importance for the development of methods for the early prevention of heart failure. The aim of our study was to study myocardial dysfunction using speckle tracking echocardiography (STE) in patients with RA and to find out possible correlations with the course of the disease and risk factors for cardiovascular diseases. Materials and methods. 29 RA patients were examined (5 in remission, 17.2%). Rheumatoid factor (RF), the level of antibodies to cyclic citrullinated peptides (a-CRP), quantitative C-reactive protein (CRP) was determined in the blood of all patients, and echocardiography and speckle-tracking echocardiography were performed to determine indicators of longitudinal deformation of the left ventricle. Disease activity was determined using the DAS28 index (CRP) and other functional and laboratory indicators. The results. The study of STE indicators is much better than "classical" echocardiography, revealing latent preclinical heart lesions. We established a significant decrease in Global Longitudinal Strain in the basal anterior and basal antero-septal segments (-17.24±3.01% and 15.94±9.37%, respectively) and preservation of local strain in the apical and middle segments (respectively -26.95+4.95% and -21.69+3.05%). In general, 41.2% of patients with RA had lesions of the basal segments. When analyzing the correlation between disease activity and deformation in STE, an inverse relationship between the DAS28 index and apical deformation (API Strain) was established (r=-0.50, р=0.06). The highest correlations were found between STE and functional status of disease: HAQ-DI score (r=-0.51, p=0.05) and VAS activity (r=-0.64, p=0.01). Conclusions. Functional activity according to the HAQ-DI score and VAS had a significantly greater relationship with preclinical manifestations of heart damage (detected by STE) than standard cardio-vascular risk factors. It is necessary to continue the search for other important factors that can lead to the formation of heart lesions and are related to both the activity of the disease and the functional status of patients. It is expedient to conduct comparative studies of STE in RA and coronary artery disease to clarify the differences in the processes of formation of myocardial damage.

Prognostic Models for Mortality and Morbidity in Heart Failure With Preserved Ejection Fraction

Accurate risk prediction of morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF) may help clinicians risk stratify and inform care decisions. To develop and validate a novel prediction model for clinical outcomes in patients with HFpEF using routinely collected variables and to compare it with a biomarker-driven approach. Data were used from the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial to derive the prediction model, and data from the Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction (PARAGON-HF) and the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-PRESERVE) trials were used to validate it. The outcomes were the composite of HF hospitalization (HFH) or cardiovascular death, cardiovascular death, and all-cause death. A total of 30 baseline candidate variables were selected in a stepwise fashion using multivariable analyses to create the models. Data were analyzed from January 2023 to June 2023. Models to estimate the 1-year and 2-year risk of cardiovascular death or hospitalization for heart failure, cardiovascular death, and all-cause death. Data from 6263 individuals in the DELIVER trial were used to derive the prediction model and data from 4796 individuals in the PARAGON-HF trial and 4128 individuals in the I-PRESERVE trial were used to validate it. The final prediction model for the composite outcome included 11 variables: N-terminal pro-brain natriuretic peptide (NT-proBNP) level, HFH within the past 6 months, creatinine level, diabetes, geographic region, HF duration, treatment with a sodium-glucose cotransporter 2 inhibitor, chronic obstructive pulmonary disease, transient ischemic attack/stroke, any previous HFH, and heart rate. This model showed good discrimination (C statistic at 1 year, 0.73; 95% CI, 0.71-0.75) in both validation cohorts (C statistic at 1 year, 0.71; 95% CI, 0.69-0.74 in PARAGON-HF and 0.75; 95% CI, 0.73-0.78 in I-PRESERVE) and calibration. The model showed similar discrimination to a biomarker-driven model including high-sensitivity cardiac troponin T and significantly better discrimination than the Meta-Analysis Global Group in Chronic (MAGGIC) risk score (C statistic at 1 year, 0.60; 95% CI, 0.58-0.63; delta C statistic, 0.13; 95% CI, 0.10-0.15; P < .001) and NT-proBNP level alone (C statistic at 1 year, 0.66; 95% CI, 0.64-0.68; delta C statistic, 0.07; 95% CI, 0.05-0.08; P < .001). Models derived for the prediction of all-cause and cardiovascular death also performed well. An online calculator was created to allow calculation of an individual's risk. In this prognostic study, a robust prediction model for clinical outcomes in HFpEF was developed and validated using routinely collected variables. The model performed better than NT-proBNP level alone. The model may help clinicians to identify high-risk patients and guide treatment decisions in HFpEF.

Association of sodium-glucose cotransporter 2 inhibitors with risk of major adverse cardiovascular events in type 2 diabetes patients with acute coronary syndrome: a propensity score‑matched analysis

BackgroundThis study aimed to investigate the association of sodium-glucose cotransporter 2 inhibitors (SGLT2i) use with cardiovascular (CV) clinical outcomes in type 2 diabetes (T2D) patients with acute coronary syndrome (ACS).MethodsData of T2D patients hospitalized for ACS at Civil Aviation General Hospital from January 2019 to December 2022 were collected. Based on SGLT2i use or not, patients were stratified as SGLT2i group and SGLT2i-free group. A 1:1 nearest-neighbor propensity score-matched (PSM) was performed to adjust for the confounding factors and facilitate the robust comparisons between groups. The first occurrence of major adverse cardiovascular events (MACE) with 1 year follow-up, which consisted of CV death, all cause death, non-fatal myocardial infarction or stroke, coronary revascularization or heart failure readmission, was assessed. Kaplan–Meier analysis and Cox regressions were conducted to evaluate the prognostic significance of SGLT2i use. Subgroup analyses were performed to assess the interaction between subgroups and SGLT2i use.ResultsA total of 925 patients were included, and the SGLT2i use increased from 9.9% in 2019 to 43.8% in 2022. 226 pairs were finally matched using the PSM model. During 1 year follow-up period, a total of 110 patients experienced MACE in the matched cohort, with a rate of 24.3%. Survival analyses showed cumulative incidence of MACE, CV death, and heart failure readmission in the SGLT2i group were significantly lower than the SGLT2i-free group. Additionally, the adjusted Cox analyses demonstrated that SGLT2i was associated with a 34.1% lower risk of MACE (HR 0.659, 95% CI 0.487–0.892, P = 0.007), which was primarily driven by a decrease in the risk of CV death by 12.0% (HR 0.880, 95% CI 0.7830.990, P = 0.033), and heart failure readmission by 45.5% (HR 0.545, 95% CI 0.332–0.893, P = 0.016). This MACE preventive benefit was consistent across different subgroups (P interaction > 0.05 for all comparisons).ConclusionsIn T2D patients with ACS, there was a clear increasing trend in SGLT2i use. SGLT2i was associated with a significantly lower risk of MACE, driven by the decrease in the risk of CV death, and heart failure readmission. Our study confirmed real-world use and efficacy of SGLT2i in a general T2D population with ACS.

Sacubitril/Valsartan-Related Hypotension in Patients With Heart Failure and Preserved or Mildly Reduced Ejection Fraction

BackgroundHypotension is a potential adverse effect of sacubitril/valsartan, but there are limited data regarding the predictors and implications of treatment-related hypotension in heart failure (HF) with mildly reduced and preserved ejection fraction. ObjectivesWe investigated predictors of treatment-associated hypotension, clinical outcomes after hypotension, and the relationship between left ventricular ejection fraction (LVEF) and incidence of hypotension in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) trial. MethodsPARAGON-HF randomized patients with chronic HF (≥45%) to sacubitril/valsartan or valsartan. Following randomization, hypotension was defined as investigator-reported hypotension with a systolic blood pressure <100 mm Hg. Predictors of hypotension were assessed using multivariable Cox models. Associations between hypotension and clinical outcomes were evaluated in time-updated Cox models. The relationship among treatment, LVEF, and incident rates of hypotension and clinical outcomes was estimated using Poisson regression models. ResultsOf 4,796 patients in PARAGON-HF, 637 (13%) experienced hypotension, more frequently in the sacubitril/valsartan arm (P < 0.001). Following documented hypotension, patients had higher risk of cardiovascular death and total HF hospitalizations (adjusted RR: 1.63; 95% CI: 1.27-2.09; P < 0.001) and all-cause death (adjusted HR: 1.62; 95% CI: 1.28-2.05; P < 0.001). LVEF modified the association between sacubitril/valsartan and risk of hypotension (Pinteraction = 0.019) such that patients with LVEF ≥60% experienced substantially higher treatment-related risks of hypotension. ConclusionsIn PARAGON-HF, a higher LVEF was associated with an increased risk of hypotension in patients treated with sacubitril/valsartan compared with valsartan. Because these subjects are also less likely to derive clinical benefit from sacubitril/valsartan, our data reinforce that the benefit/risk ratio favors the use of sacubitril/valsartan in patients with LVEF below normal, but not at higher LVEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)

Right Ventricular Dysfunction in Patients With Concomitant Tricuspid Regurgitation Undergoing Transcatheter Aortic Valve Implantation.

This study investigated the impact and predictive factors of concomitant significant tricuspid regurgitation (TR) and evaluated the roles of right ventricle (RV) function and the etiology of TR in the clinical outcomes of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). We assessed grading of TR severity, TR etiology, and RV function in pre- and post-TAVI transthoracic echocardiograms for 678 patients at Keio University School of Medicine. TR etiology was divided into 3 groups: primary TR, ventricular functional TR (FTR), and atrial FTR. The primary outcomes were all-cause and cardiovascular death. At baseline, moderate or greater TR was found in 55 (8%) patients and, after adjustment for comorbidities, was associated with increased all-cause death (hazard ratio [HR] 2.11; 95% confidence interval [CI] 1.19-3.77; P=0.011) and cardiovascular death (HR 2.29; 95% CI 1.06-4.99; P=0.036). RV dysfunction (RVD) also remained an independent predictor of cardiovascular death (HR 2.06; 95% CI 1.03-4.14; P=0.042). Among the TR etiology groups, patients with ventricular FTR had the lowest survival rate (P<0.001). Patients with persistent RVD after TAVI had a higher risk of cardiovascular death than those with a normal or recovered RV function (P<0.001). The etiology of TR and RV function play an important role in predicting outcomes in concomitant TR patients undergoing TAVI.

Association between the haemoglobin glycation index (HGI) and clinical outcomes in patients with acute decompensated heart failure

Background A growing number of studies show that people with similar blood glucose levels have different levels of glycosylated haemoglobin (HbA1c), and relying only on HbA1c may lead to clinical decision-making errors. The haemoglobin glycation index (HGI) quantifies the difference in HbA1c among individuals and is strongly linked to the risk of cardiovascular disease. However, the connection between this phenomenon and the poor outcomes of patients with acute decompensated heart failure (ADHF) is currently unknown. Patients and Methods This retrospective, single-centre-based cohort study included 1531 hospitalized patients with ADHF from September 2010 to January 2020. The HGI is calculated from the difference between the observed and predicted HbA1c values [predicted HbA1c = 0.024 × fasting plasma glucose (FPG) (mg/dL)+3.1]. The endpoints examined in the study included all-cause death, cardiovascular (CV) death, and major adverse cardiac events (MACE). We fitted multivariable-adjusted Cox proportional hazard models to investigate the association between the HGI and clinical outcomes. Results During the five-year follow-up, 427 (27.9%) patients died from all causes, 232 (15.6%) from CV death, and 848 (55.4%) from MACE. The restricted cubic spline analysis also showed that the cumulative risk of all-cause and CV deaths decreased linearly with increasing HGI. According to multivariate Cox proportional hazard models, the highest tertile of the HGI was associated with a lower incidence of all-cause and cardiovascular deaths [all-cause death, adjusted hazard ratio (HR): 0.720, 95% confidence interval (CI): 0.563–0.921, p = 0.009; CV death, adjusted HR: 0.619, 95% CI: 0.445–0.861, p = 0.004]. A 1% increase in the HGI was associated with a 12.5% reduction in the risk of all-cause death and a 20.8% reduction in the risk of CV death. Conclusions A high HGI was directly associated with a reduction in all-cause and CV deaths but was not associated with MACE. These findings may be helpful in the management of patients with ADHF.

Impact of heart rate changes during hospitalization on outcome in heart failure with preserved ejection fraction.

The benefits of lowering heart rate (HR) in heart failure (HF) with preserved ejection fraction (HFpEF) patients are still a matter of debate. This study aimed to investigate the relationship between changes in HR during hospitalization and cardiovascular (CV) events and all-cause death in hospitalized HFpEF patients. Hospitalized HF patients between January 2017 and December 2021 were consecutively enrolled in a national, multicentred, and prospective registry database, the China Cardiovascular Association Database-HF Center Registry. HF patients with a left ventricular ejection fraction of ≥50% were defined as HFpEF patients. The study analysed admission/discharge HR, change in HR during hospitalization (∆HR), and ∆HR ratio (∆HR/admission HR). The patients were categorized into three groups: no HR dropping group (ΔHR ratio>0.0%), moderate HR dropping group (-15%<ΔHR ratio≤0.0%), and excessive HR dropping group (ΔHR ratio≤-15%). All patients were followed up for 12months. The primary endpoint was CV events (CV death or HF rehospitalization). The secondary endpoint was all-cause death. A total of 19510 HFpEF patients (9750 males, mean age 71.9±12.2years) were included, with 4575 in the no HR dropping group, 8434 in the moderate HR dropping group, and 6501 in the excessive HR dropping group. Excessive HR dropping during hospitalization was significantly associated with an increased risk of CV events (17.1%) compared with the no HR dropping group (14.5%, P<0.001) or the moderate HR dropping group (14.0%, P<0.001), although all-cause mortality was similar among the three groups. After adjusting for multiple confounding factors, excessive HR dropping remained an independent predictor of increased CV event risk [hazard ratio 1.197, 95% confidence interval (CI) 1.078-1.328]. Subgroup analysis revealed that the prognostic impact of excessive HR dropping on increased CV event risk remained in the subgroups of older age, New York Heart Association class IV, ischaemic HF, higher left ventricular ejection fraction, absence of chronic kidney disease, and use of beta-blockers or ivabradine. Independent determinants associated with excessive HR dropping during admission included use of beta-blockers [odds ratio (OR) 1.683, 95% CI 1.558-1.819], lower discharge diastolic blood pressure (OR 0.988, 95% CI 0.985-0.991), no pacemaker (OR 0.501, 95% CI 0.416-0.603), coexisting atrial fibrillation or atrial flutter (OR 1.327, 95% CI 1.218-1.445), and use of digoxin (OR 1.340, 95% CI 1.213-1.480). In hospitalized HFpEF patients, excessive HR dropping during hospitalization is associated with an increased risk of CV death or HF rehospitalization. These findings highlight the importance of HR monitoring and avoiding excessively slowing down HR in hospitalized HFpEF patients to reduce the risk of CV events.

Long-Term Body Mass Index Variability and Adverse Cardiovascular Outcomes

Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is a commonly used estimate of obesity, which is a complex trait affected by genetic and lifestyle factors. Marked weight gain and loss could be associated with adverse biological processes. To evaluate the association between BMI variability and incident cardiovascular disease (CVD) events in 2 distinct cohorts. This cohort study used data from the Million Veteran Program (MVP) between 2011 and 2018 and participants in the UK Biobank (UKB) enrolled between 2006 and 2010. Participants were followed up for a median of 3.8 (5th-95th percentile, 3.5) years. Participants with baseline CVD or cancer were excluded. Data were analyzed from September 2022 and September 2023. BMI variability was calculated by the retrospective SD and coefficient of variation (CV) using multiple clinical BMI measurements up to the baseline. The main outcome was incident composite CVD events (incident nonfatal myocardial infarction, acute ischemic stroke, and cardiovascular death), assessed using Cox proportional hazards modeling after adjustment for CVD risk factors, including age, sex, mean BMI, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking status, diabetes status, and statin use. Secondary analysis assessed whether associations were dependent on the polygenic score of BMI. Among 92 363 US veterans in the MVP cohort (81 675 [88%] male; mean [SD] age, 56.7 [14.1] years), there were 9695 Hispanic participants, 22 488 non-Hispanic Black participants, and 60 180 non-Hispanic White participants. A total of 4811 composite CVD events were observed from 2011 to 2018. The CV of BMI was associated with 16% higher risk for composite CVD across all groups (hazard ratio [HR], 1.16; 95% CI, 1.13-1.19). These associations were unchanged among subgroups and after adjustment for the polygenic score of BMI. The UKB cohort included 65 047 individuals (mean [SD] age, 57.30 (7.77) years; 38 065 [59%] female) and had 6934 composite CVD events. Each 1-SD increase in BMI variability in the UKB cohort was associated with 8% increased risk of cardiovascular death (HR, 1.08; 95% CI, 1.04-1.11). This cohort study found that among US veterans, higher BMI variability was a significant risk marker associated with adverse cardiovascular events independent of mean BMI across major racial and ethnic groups. Results were consistent in the UKB for the cardiovascular death end point. Further studies should investigate the phenotype of high BMI variability.

Dapagliflozin versus sacubitril-valsartan for heart failure with mildly reduced or preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with an increased risk of heart failure (HF) hospitalizations and cardiovascular death (CVD). Both dapagliflozin and sacubitril-valsartan have recently shown convincing reductions in the combined risk of CVD and HF hospitalizations in patients with HF and mildly reduced ejection fraction (HFmrEF) or HFpEF. We aimed to investigate the cost-per-outcome implications of dapagliflozin vs sacubitril-valsartan in the treatment of HFmrEF or HFpEF patients. We compared the annualized cost needed to treat (CNT) to prevent the composite outcome of total HF hospitalizations and CVD with dapagliflozin or sacubitril-valsartan. The CNT was estimated by multiplying the annualized number needed to treat (aNNT) by the annual cost of therapy. The aNNT was calculated based on data collected from the DELIVER trial for dapagliflozin and a pooled analysis of the PARAGLIDE-HF and PARAGON-HF trials for sacubitril-valsartan. Costs were based on 2022 US prices. Scenario analyses were performed to attenuate the differences in the studies' populations. The aNNT with dapagliflozin in DELIVER was 30 (95% confidence interval [CI]: 21-62) versus 44 (95% CI: 25-311) with sacubitril-valsartan in a pooled analysis of PARAGLIDE-HF and PARAGON-HF, with an annual cost of $4,951 and $5,576, respectively. The corresponding CNTs were $148,547.13 (95% CI: $103,982.99-$306,997.39) for dapagliflozin and $245,346.77 (95% CI: $139,401.58-1,734,155.60) for sacubitril-valsartan for preventing the composite outcome of CVD and HF hospitalizations. The CNT for preventing all-cause mortality was lower for dapagliflozin than sacubitril-valsartan $1,128,958.15 [CI: $401,077.24-∞] vs $2,185,816.71 [CI: $607,790.87-∞]. Dapagliflozin provides a better monetary value than sacubitril-valsartan in preventing the composite outcome of total HF hospitalizations and CVD among patients with HFmrEF or HFpEF.

Abstract P377: Association Between Area Deprivation and Premature Cardiovascular Mortality in South Korea

Background: The underlying factors for regional disparities in cardiovascular disease (CVD) have yet to be fully understood. There is limited research on the effect of regional-level socioeconomic conditions on CVD mortality. This ecological study aims to investigate the association between area deprivation and premature death from CVD. Methods: The deprivation index was formulated with 10 socioeconomic indicators across all the 250 municipalities in Korea. Mortality rates from total CVD, ischemic heart disease, and cerebrovascular disease in adults &lt;65 years were directly standardized for sex and age using the total population structure. Municipalities are stratified by urbanicity, and the number of hospitals and the size of an area were adjusted in log-linear regression models. Results: The most deprived municipalities showed 41.6% excess mortality for total CVD, 30.3% for ischemic heart disease, and 36.9% for cerebrovascular disease, compared to the least deprived ones. Even after adjusting for the number of hospitals per unit area, the association of area deprivation was more significant in metropolitan areas than in other provinces. As one increment of the deprivation index increased, the adjusted rate ratios for total CVD were 1.031 (1.020-1.043) in metropolitans and 1.009 (1.000-1.019) in other provinces. Additional multilevel analyses showed consistent findings of higher risks in deprived areas. Conclusions: This study highlights a higher risk of premature cardiovascular death in socioeconomically disadvantaged areas. The CVD prevention strategies should reflect regional characteristics, with a particular focus on reducing the burden in deprived metropolitan areas.

Wildfire-related PM2.5 and cardiovascular mortality: A difference-in-differences analysis in Brazil

Brazil has experienced unprecedented wildfires recently. We aimed to investigate the association of wildfire-related fine particulate matter (PM2.5) with cause-specific cardiovascular mortality, and to estimate the attributable mortality burden. Exposure to wildfire-related PM2.5 was defined as exposure to annual mean wildfire-related PM2.5 concentrations in the 1-year prior to death. The variant difference-in-differences method was employed to explore the wildfire-related PM2.5-cardiovascular mortality association. We found that, in Brazil, compared with the population in the first quartile (Q1: ≤1.82 μg/m3) of wildfire-related PM2.5 exposure, those in the fourth quartile (Q4: 4.22–17.12 μg/m3) of wildfire-related PM2.5 exposure had a 2.2% (RR: 1.022, 95% CI: 1.013–1.032) higher risk for total cardiovascular mortality, 3.1% (RR: 1.031, 95% CI: 1.014–1.048) for ischaemic heart disease mortality, and 2.0% (RR: 1.020, 95% CI: 1.002–1.038) for stroke mortality. From 2010 to 2018, an estimation of 35,847 (95% CI: 22,424–49,177) cardiovascular deaths, representing 17.77 (95% CI: 11.12–24.38) per 100,000 population, were attributable to wildfire-related PM2.5 exposure. Targeted health promotion strategies should be developed for local governments to protect the public from the risk of wildfire-related cardiovascular premature deaths.

Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model.

Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors. To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients. This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated via decision curve analysis (DCA). The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), P < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), P = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), P = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), P = 0.019; > 5 cm: 2.090 (1.543-2.830), P < 0.001], surgery (no) [0.376 (0.297-0.476), P < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), P < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit. Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions.

Autoimmune blistering disorders and cardiovascular risks: A population-based cohort study

BackgroundAutoimmune blistering disorders (ABDs) might elevate cardiovascular risk, but studies are lacking. ObjectiveTo examine if ABDs elevate the risk of atherosclerotic cardiovascular disease (ASCVD), heart failure, arrhythmia, venous thromboembolism, and cardiovascular death. MethodsA population-based cohort of Danish patients with ABD (≥18 years of age) diagnosed during 1996–2021 (n=3,322) was compared with an age and sex-matched comparison cohort from the general population (n=33,195). ResultsCompared with the general population, patients with ABDs had higher one-year risks of ASCVD (3.4% vs. 1.6%), heart failure (1.9% vs. 0.7%), arrhythmia (3.8% vs. 1.3%), venous thromboembolism (1.9% vs. 0.3%), and cardiovascular death (3.3% vs. 0.9%). The elevated risk persisted after 10 years for all outcomes but arrhythmia. The hazard ratios associating ABD with the outcomes during the entire follow-up were 1.24 (1.09–1.40) for ASCVD, 1.48 (1.24–1.77) for heart failure, 1.16 (1.02–1.32) for arrhythmia, 1.87 (1.50–2.34) for VTE, and 2.01 (1.76–2.29) for cardiovascular death. The elevated cardiovascular risk was observed for both pemphigus and pemphigoid. LimitationsOur findings might only generalize to patients with ABDs without prevalent cardiovascular diseases. ConclusionPatients with ABDs had an elevated cardiovascular risk compared with age and sex-matched controls.

Dapagliflozin in patients with heart failure and previous myocardial infarction: A participant-level pooled analysis of DAPA-HF and DELIVER.

Patients with heart failure (HF) and history of myocardial infarction (MI) face a higher risk of disease progression and clinical events. Whether sodium-glucose cotransporter 2 inhibitors may modify clinical trajectory in such individuals remains incompletely understood. The DAPA-HF and DELIVER trials compared dapagliflozin with placebo in patients with symptomatic HF with left ventricular ejection fraction (LVEF) ≤40% and > 40%, respectively. In this pooled participant-level analysis, we assessed efficacy and safety outcomes by history of MI. The primary outcome in both trials was the composite of cardiovascular death or worsening HF. Of the total of 11 007 patients, 3731 (34%) had a previous MI and were at higher risk of the primary outcome across the spectrum of LVEF in covariate-adjusted models (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.02-1.24). Dapagliflozin reduced the risk of the primary outcome to a similar extent in patients with (HR 0.83, 95% CI 0.72-0.96) and without previous MI (HR 0.76, 95% CI 0.68-0.85; pinteraction = 0.36), with consistent benefits on key secondary outcomes as well. Serious adverse events did not occur more frequently with dapagliflozin, irrespective of previous MI. History of MI confers increased risks of adverse cardiovascular outcomes in patients with HF across the LVEF spectrum, even among those with preserved ejection fraction. Dapagliflozin consistently and safely reduces the risk of cardiovascular death or worsening HF, regardless of previous MI.

Donepezil attenuates progression of cardiovascular remodeling and improves prognosis in spontaneously hypertensive rats with chronic myocardial infarction.

The acetylcholinesterase inhibitor donepezil restores autonomic balance, reduces inflammation, and improves long-term survival in rats with chronic heart failure (CHF) following myocardial infarction (MI). As arterial hypertension is associated with a significant risk of cardiovascular death, we investigated the effectiveness of donepezil in treating CHF in spontaneously hypertensive rats (SHR). CHF was induced in SHR by inducing permanent MI. After 2 weeks, the surviving SHR were randomly assigned to sham-operated (SO), untreated (UT), or oral donepezil-treated (DT, 5 mg/kg/day) groups, and various vitals and parameters were monitored. After 7 weeks of treatment, heart rate and arterial hypertension reduced significantly in DT rats than in UT rats. Donepezil treatment improved 50-day survival (41% to 80%, P = 0.004); suppressed progression of cardiac hypertrophy, cardiac dysfunction (cardiac index: 133 ± 5 vs. 112 ± 5 ml/min/kg, P < 0.05; left ventricular end-diastolic pressure: 12 ± 3 vs. 22 ± 2 mmHg, P < 0.05; left ventricular +dp/dtmax: 5348 ± 338 vs. 4267 ± 114 mmHg/s, P < 0.05), systemic inflammation, and coronary artery remodeling (wall thickness: 26.3 ± 1.4 vs. 34.7 ± 0.7 μm, P < 0.01; media-to-lumen ratio: 3.70 ± 0.73 vs. 8.59 ± 0.84, P < 0.001); increased capillary density; and decreased plasma catecholamine, B-type natriuretic peptide, arginine vasopressin, and angiotensin II levels. Donepezil treatment attenuated cardiac and coronary artery remodeling, mitigated cardiac dysfunction, and significantly improved the prognosis of SHR with CHF.

Opportunities to Reduce the Risk of Cardiovascular Death by Improving Machine Learning Methods

Improving algorithms for automatic recognition of electrocardiograms requires increasing of training dataset, which is not always possible due to the rarity of certain cardiac diseases or ethical issues. It is possible to improve the algorithms for generating synthetic electrocardiograms using mechanistic models and generative-descriptive neural networks (GANs). At the same time, when evaluating the effectiveness of the proposed solutions, various authors offer different quality assessment metrics from subjective expert assessment to the squared mean error. We compare two approaches to generating synthetic electrocardiograms: pseudo-ECG generation using a one-dimensional cardiomyocyte model and GAN based on long-term short-term memory in terms of machine learning metrics: accuracy, recall, f1-score. We solve the problem of binary classification with bagging method, class 0 — normal sinus rhythm, class 1 — atrial fibrillation. We found that classifier trained on synthetic ECGs generated using GAN is slightly more effective compared to pseudo-ECGs generated using mechanistic models ones. At the same time, it turned out that GANs are not stable enough. The generation of synthetic electrocardiograms using both mechanistic models and GAN can be used to enrich the training set in case of recognition of rare cardiac diseases.

The clinical benefits of sodium-glucose cotransporter type 2 inhibitors in people with gout.

Gout is the most common form of inflammatory arthritis worldwide and is characterized by painful recurrent flares of inflammatory arthritis that are associated with a transiently increased risk of adverse cardiovascular events. Furthermore, gout is associated with multiple cardiometabolic-renal comorbidities such as type 2 diabetes, chronic kidney disease and cardiovascular disease. These comorbidities, potentially combined with gout flare-related inflammation, contribute to persistent premature mortality in gout, independently of serum urate concentrations and traditional cardiovascular risk factors. Although better implementation of standard gout care could improve gout outcomes, deliberate efforts to address the cardiovascular risk in patients with gout are likely to berequired to reduce mortality. Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are approved for multiple indications owing to their ability to lower the risk of all-cause and cardiovascular death, hospitalizations for heart failure and chronic kidney disease progression, making them an attractive treatment option for gout. These medications have also been shown to lower serum urate concentrations, the causal culprit in gout risk, and are associated with a reduced risk of incident and recurrent gout, potentially owing to their purported anti-inflammatory effects. Thus, SGLT2 inhibition could simultaneously address both the symptoms of gout and its comorbidities.

The worsening effect of paroxysmal atrial fibrillation on left ventricular function and deformation in type 2 diabetes mellitus patients: a 3.0 T cardiovascular magnetic resonance feature tracking study

BackgroundAtrial fibrillation (AF) has been linked to an increased risk of cardiovascular death, overall mortality and heart failure in patients with type 2 diabetes mellitus (T2DM). The present study investigated the additive effects of paroxysmal AF on left ventricular (LV) function and deformation in T2DM patients with or without AF using the cardiovascular magnetic resonance feature tracking (CMR-FT) technique.MethodsThe present study encompassed 225 T2DM patients differentiated by the presence or absence of paroxysmal AF [T2DM(AF+) and T2DM(AF−), respectively], along with 75 age and sex matched controls, all of whom underwent CMR examination. LV function and global strains, including radial, circumferential and longitudinal peak strain (PS), as well as peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were measured and compared among the groups. Multivariable linear regression analysis was used to examine the factors associated with LV global strains in patients with T2DM.ResultsThe T2DM(AF+) group was the oldest, had the highest LV end‑systolic volume index, lowest LV ejection fraction and estimated glomerular filtration rate compared to the control and T2DM(AF−) groups, and presented a shorter diabetes duration and lower HbA1c than the T2DM(AF−) group. LV PS-radial, PS-longitudinal and PDSR-radial declined successively from controls through the T2DM(AF−) group to the T2DM(AF+) group (all p < 0.001). Compared to the control group, LV PS-circumferential, PSSR-radial and PDSR-circumferential were decreased in the T2DM(AF+) group (all p < 0.001) but preserved in the T2DM(AF−) group. Among all clinical indices, AF was independently associated with worsening LV PS-longitudinal (β = 2.218, p < 0.001), PS-circumferential (β = 3.948, p < 0.001), PS-radial (β = − 8.40, p < 0.001), PSSR-radial and -circumferential (β = − 0.345 and 0.101, p = 0.002 and 0.014, respectively), PDSR-radial and -circumferential (β = 0.359 and − 0.14, p = 0.022 and 0.003, respectively).ConclusionsIn patients with T2DM, the presence of paroxysmal AF further exacerbates LV function and deformation. Proactive prevention, regular detection and early intervention of AF could potentially benefit T2DM patients.

Carbohydrate antigen 125 concentrations across the ejection fraction spectrum in chronic heart failure: The EMPEROR programme.

Vascular congestion may lead to an increase of carbohydrate antigen 125 (CA-125). The role of CA-125 as a biomarker of congestion or for prognosis across the full ejection fraction (EF) spectrum of chronic heart failure (HF) remains unknown. Serum CA-125 was measured in 1111 study participants from the EMPEROR-Reduced and EMPEROR-Preserved trials. Congestive signs and symptoms were evaluated across CA-125 tertiles. Cox regression was used to study the association with outcomes. The primary outcome was a composite of first HF hospitalization or cardiovascular (CV) death. No significant association was present between baseline CA-125 levels and congestive signs or symptoms. In the overall population, higher CA-125 levels were not associated with an increased risk of primary outcome (tertile 3 vs. tertile 1: hazard ratio [HR] 1.34; 95% confidence interval [CI] 0.91-1.96; p-trend = 0.11). However, higher CA-125 levels were associated with an increased risk of primary outcome in patients with HF and reduced EF (HFrEF; tertile 3 vs. tertile 1: HR 2.25 [95% CI 1.30-3.89]), but not among patients with preserved EF (HFpEF; tertile 3 vs. tertile 1: HR 0.68 [95% CI 0.38-1.21]); interaction-p = 0.02). Patients in the upper CA-125 tertile also showed the steepest estimated glomerular filtration rate decline over time (p-trend = 0.03). The effect of empagliflozin to reduce the risk of CV death or HF hospitalization appeared to be attenuated in those with lower baseline CA-125 levels (interaction-p-trend = 0.09). Across the range of EF in patients with chronic HF enrolled in the EMPEROR trials, the majority of whom did not have clinical evidence of congestion, CA-125 concentrations were not significantly associated with congestive signs or symptoms. CA-125 concentrations may predict HF hospitalization/CV death in patients with HFrEF, but not those with HFpEF. EMPEROR-Reduced (NCT03057977), EMPEROR-Preserved (NCT03057951).

Long-Term Effects of Sacubitril/Valsartan After Chemotherapy for Breast Cancer in Patients With Chronic heart Failure

Background: As the survival of patients with malignant neoplasms is improving, the urgent need for cardioprotective agents to counteract toxic effects of chemotherapy is growing.Objective: To compare the cardioprotective efficacy of sacubitril/valsartan and candesartan in women with chronic heart failure and baseline reduced left ventricular ejection fraction (LVEF) during a 5-year prospective follow-up after chemotherapy for breast cancer.Materials and methods: In this randomized study, 127 women with chronic heart failure and reduced LVEF after radical surgical treatment of breast cancer received potentially cardiotoxic adjuvant polychemotherapy (fluorouracil+ doxorubicin + cyclophosphamide). In addition, the patients received sacubitril/valsartan at a dose of up to 97/103 mg twice daily (n = 63) or candesartan at a dose of up to 32 mg once daily (n = 65), and this treatment was monitored for 5 years.Results: The combination of sacubitril/valsartan was significantly superior to candesartan in improving left ventricular function and reducing the burden of ventricular arrhythmias and the risk of cardiovascular death (P = .039) at the long-term follow-up. Sacubitril/valsartan group and candesartan group did not differ in terms of mortality due to breast cancer progression or recurrence (P = .628).Conclusions: Sacubitril/valsartan can be considered an effective and safe option for protecting the cardiovascular system during potentially cardiotoxic polychemotherapy for breast cancer in patients with chronic heart failure and baseline reduced LVEF.