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Heart failure and chronic kidney disease are common and clinically important conditions that regularly coexist. Electrophysiologic changes of advanced heart failure often result in abnormal conduction, causing dyssynchronous contraction, and development of ventricular arrhythmias, which can lead to sudden cardiac arrest. In the last 2 decades, implantable cardioverter-defibrillator and cardiac resynchronization therapy devices have been developed to address these complications. However, when the coexisting chronic kidney disease is advanced, the associated pathophysiologic cardiovascular changes can alter the efficacy and safety of those interventions and complicate the management. This review explores the impact of comorbid advanced heart failure and advanced chronic kidney disease on the efficacy and safety of implantable cardioverter-defibrillator and cardiac resynchronization therapy, the currently available evidence, and potential future directions., Competing Interests: Funding Support and Author Disclosures Dr Cleland has received research grants from Bristol Myers Squibb, CSL-Vifor, and Pharmacosmos; and has received honoraria for advisory boards and speaking from Biopeutics, Boehringer Ingelheim, Bristol Myers Squibb, CSL-Vifor, and Pharmacosmos. Dr Abraham has received personal fees from Medtronic and Abbott. Dr Lip is a consultant and speaker for Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Anthos, no fees are received personally; is a National Institute for Health and Care Research (NIHR) Senior Investigator and coprincipal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899871. Dr Hatamizadeh has served as advisory board member for Horizon Therapeutics; and receives research support from Sarfez Pharmaceutical Company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Heart failure (HF) and malnutrition exhibit overlapping risk factors, characterized by increased levels of natriuretic peptides and an inflammatory profile. The aim of this study was to compare the differences in plasma brain natriuretic peptide (BNP), N-terminal-pro B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) in patients with HF and malnutrition versus normal nutrition., Methods: From inception until July 2023, the databases, PubMed, Scopus, Web of Science, and Cochrane Library were searched. To examine the association among malnutrition [controlling nutritional status (CONUT) score ≥2; Geriatric Nutritional Risk Index (GNRI) score <92] with BNP, NT-proBNP and CRP in patients with HF, a meta-analysis using a random-effects model was conducted (CRD42023445076)., Results: A significant association of GNRI with increased levels of BNP were demonstrated [mean difference (MD): 204.99, 95% confidence interval (CI) (101.02, 308.96, I 2  = 88%, P < 0.01)], albeit no statistically significant findings were shown using CONUT [MD: 158.51, 95% CI (-1.78 to 318.79, I 2  = 92%, P = 0.05)]. GNRI [MD: 1885.14, 95% CI (1428.76-2341.52, I 2  = 0%, P < 0.01)] and CONUT [MD: 1160.05, 95% CI (701.04-1619.07, I 2  = 0%, P < 0.01)] were associated with significantly higher levels of NT-proBNP. Patients with normal GNRI scores had significantly lower levels of CRP [MD: 0.50, 95% CI (0.12-0.88, I 2  = 87%, P = 0.01)] whereas significantly higher levels of CRP were observed in those with higher CONUT [MD: 0.40, 95% CI (0.08-0.72, I 2  = 88%, P = 0.01)]. Employing meta-regression, age was deemed a potential moderator between CRP and GNRI., Conclusions: Normal nutrition scores in patients with HF are linked to lower BNP, NT-proBNP, and CRP levels compared with malnourished counterparts. Despite the significant link between CRP and malnutrition, their relationship may be influenced in older groups considering the sensitivity of GNRI due to ageing factors., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim: To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD)., Methods: We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry., Results: Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status., Conclusions: In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD., (© 2024 John Wiley & Sons Ltd.)

Aims: Sarcopenia is linked to impaired physical function and exercise tolerance. The aim of this systematic review and meta-analysis was to examine the association of sarcopenia and low appendicular skeletal muscle (ASM) with biomarkers of cardiac function, B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP), in patients with heart failure (HF)., Methods and Results: From inception until May 2023, a systematic literature search of observational studies was undertaken utilizing the PubMed, Web of Science, Scopus, and Cochrane Library databases. A meta-analysis employing a random-effects model was used to compute the pooled effects (CRD42023418465). Overall, 16 studies were included in this systematic review and meta-analysis. Our main analysis showed that sarcopenia in HF was linked to significantly higher levels of BNP (MD: 87.76, 95% CI 20.74-154.78, I 2 = 61%, P = 0.01) and NT-proBNP (MD: 947.45, 95% CI 98.97-1795.93, I 2 = 35%, P = 0.03). Similarly, low ASM was associated with significantly higher levels of BNP (MD: 118.95, 95% CI 46.91-191.00, I 2 = 93%, P < 0.01) and NT-proBNP (MD: 672.01, 95% CI 383.72-960.30, I 2 = 2%, P < 0.01). The quality of the included cohort studies was considered moderate, using the binary AXIS checklist and the Cochrane Tool to Assess the Risk of Bias in Cohort Studies., Conclusions: In patients with HF, sarcopenia and reduced ASM are associated with considerably higher plasma levels of BNP and NT-proBNP. Future research is required to investigate whether sarcopenia may express dysregulated biomarkers of cardiac function., (© 2024. The Author(s).)

Patients with heart failure with reduced ejection fraction (HFrEF) and diabetes mellitus (DM) have an increased risk of adverse events, including thromboembolism. In this analysis, we aimed to explore the association between DM and HFrEF using data from the "Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction" (WARCEF) trial. We analyzed factors associated with DM using multiple logistic regression models and evaluated the effect of DM on long-term prognosis, through adjusted Cox regressions. The primary outcome was the composite of all-cause death, ischemic stroke, or intracerebral hemorrhage; we explored individual components as the secondary outcomes and the interaction between treatment (warfarin or aspirin) and DM on the risk of the primary outcome, stratified by relevant characteristics. Of 2294 patients (mean age 60.8 (SD 11.3) years, 19.9% females) included in this analysis, 722 (31.5%) had DM. On logistic regression, cardiovascular comorbidities, symptoms and ethnicity were associated with DM at baseline, while age and body mass index showed a nonlinear association. Patients with DM had a higher risk of the primary composite outcome (Hazard Ratio [HR] and 95% Confidence Intervals [CI]: 1.48 [1.24-1.77]), as well as all-cause death (HR [95%CI]: 1.52 [1.25-1.84]). As in prior analyses, no statistically significant interaction was observed between DM and effect of Warfarin on the risk of the primary outcome, in any of the subgroups explored. In conclusion, we found that DM is common in HFrEF patients, and is associated with other cardiovascular comorbidities and risk factors, and with a worse prognosis., (© 2024. The Author(s).)

Aims: The influence of social determinants of health (SDOH) on the prognosis of Heart Failure and reduced Ejection Fraction (HFrEF) is increasingly reported. We aim to evaluate the contribution of educational status on outcomes in patients with HFrEF., Methods: We used data from the WARCEF trial, which randomized HFrEF patients with sinus rhythm to receive Warfarin or Aspirin; educational status of patients enrolled was collected at baseline. We defined three levels of education: low, medium and high level, according to the highest qualification achieved or highest school grade attended. We analysed the impact of the educational status on the risk of the primary composite outcome of all-cause death, ischemic stroke (IS) and intracerebral haemorrhage (ICH); components of the primary outcome were also analysed as secondary outcomes., Results: 2295 patients were included in this analysis; of these, 992 (43.2%) had a low educational level, 947 (41.3%) had a medium education level and the remaining 356 (15.5%) showed a high educational level. Compared to patients with high educational level, those with low educational status showed a high risk of the primary composite outcome (adjusted hazard ratio [aHR]: 1.31, 95% confidence intervals [CI] 1.02-1.69); a non-statistically significant association was observed in those with medium educational level (aHR: 1.20, 95%CI: .93-1.55). Similar results were observed for all-cause death, while no statistically significant differences were observed for IS or ICH., Conclusion: Compared to patients with high educational levels, those with low educational status had worse prognosis. SDOH should be considered in patients with HFrEF., Clinical Trial Registration: NCT00041938., (© 2024 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: Data on cardiovascular outcomes according to objectively measured physical activity (PA) in patients with atrial fibrillation (AF) are scarce. This study explored the associations between PA derived from wrist-worn accelerometers and the risk of death, incident heart failure (HF), and incident stroke in patients with AF., Methods: From 37 990 patients with AF in UK Biobank, 2324 patients with accelerometer data were included. Weekly moderate-to-vigorous PA (MVPA) duration was computed from accelerometer data. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, incident HF, and incident stroke. Restricted cubic splines estimated the dose-response associations between MVPA duration and the outcomes. The adjusted HRs (aHRs) of the outcomes according to adherence to PA standard guidelines (performing MVPA≥150 min/week) were also evaluated., Results: The mean age was 66.9±6.2 years and 64.9% were male. During a median follow-up of 6.7 years, there were 181 all-cause deaths, 62 cardiovascular deaths, 225 cases of incident HF, and 91 cases of incident stroke; the overall incidence rate per 1000 patient-years was 11.76, 4.03, 15.16 and 5.99, respectively. There was a linear inverse dose-response relationship between MVPA (≥108 min/week) and all-cause mortality. Performing MVPA for 105-590 min/week was associated with a lower risk of HF than those with no measurable MVPA. The risk of stroke and cardiovascular mortality was not associated with MVPA. Performing guideline-adherent MVPA was related to a 30% lower risk of all-cause mortality (aHR: 0.70 (0.50-0.98), p=0.04) and 33% lower risk of HF (aHR 0.67 (0.49-0.93), p=0.02)., Conclusion: In patients with AF, accelerometer-derived PA data supports lower risks of all-cause mortality and HF according to a greater level of MVPA and adherence to PA guidelines. Regular MVPA should be encouraged in patients with AF as a part of integrated management., Competing Interests: Competing interests: E-KC: Research grants or speaking fees from Abbott, Bayer, BMS/Pfizer, Biosense Webster, Chong Kun Dang, Daewoong Pharmaceutical Co, Daiichi-Sankyo, DeepQure, Dreamtech Co, Ltd, Jeil Pharmaceutical Co Ltd, Medtronic, Samjinpharm, Seers Technology, and Skylabs. GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Anthos and Daiichi-Sankyo. No fees are received personally. GYHL is coprincipal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899871., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of adverse events in patients with atrial fibrillation (AF); however, few data are available on this topic in Asian populations., Methods and Results: Prospective observational study conducted on patients with AF enrolled in the Asia-Pacific Heart Rhythm Society (APHRS) AF Registry. The diagnosis of COPD was based on data reported in the case report form by the investigators. Cox-regression models were used to assess the 1-year risk of a primary composite outcome of all-cause death, thromboembolic events, acute coronary syndrome, and heart failure. Analysis on single outcomes and cardiovascular death was also performed. Interaction analysis was used to assess the risk of composite outcome and all-cause death in different subgroups. The study included 4094 patients with AF (mean±SD age 68.5±12 years, 34.6% female), of whom 112 (2.7%) had COPD. Patients with COPD showed a higher incidence of the primary composite outcome (25.1% versus 6.3%, P <0.001), all-cause death (14.9% versus 2.6%, P <0.001), cardiovascular death (2.0% versus 0.6%, P <0.001), and heart failure (8.3% versus 6.0%, P <0.001). On multiple Cox-regression analysis, COPD was associated with a higher risk of the primary composite outcome (hazard ratio [HR], 3.17 [95% CI, 2.05-4.90]), all-cause death (HR, 3.59 [95% CI, 2.04-6.30]), and heart failure (HR, 3.32 [95% CI, 1.56-7.03]); no statistically significant differences were found for other outcomes. The association between COPD and mortality was significantly modified by the use of beta blockers ( P int =0.018)., Conclusions: In Asian patients with AF, COPD is associated with worse prognosis. In patients with AF and COPD, the use of beta blockers was associated with a lower mortality., Registration Information: clinicaltrials.gov Identifier: NCT04807049.

Background and Aims: Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF., Methods: Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort., Results: The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death)., Conclusions: CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: No studies have investigated the association between albumin levels and the risk of early cardiovascular complications in patients with ischemic stroke., Methods: Retrospective analysis with a federated research network (TriNetX) based on electronic medical records ( International Classification of Diseases-Tenth Revision-Clinical Modification and logical observation identifiers names and codes) mainly reported between 2000 and 2023, from 80 health care organizations in the United States. Based on albumin levels measured at admission to the hospital, patients with ischemic stroke were categorized into 2 groups: (1) reduced (≤3.4 g/dL) and (2) normal (≥3.5 g/dL) albumin levels. The primary outcome was a composite of all-cause death, heart failure, atrial fibrillation, ventricular arrhythmias, myocardial infarction, and Takotsubo cardiomyopathy 30 days from the stroke. Secondary outcomes were the risk for each component of the primary outcome. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching., Results: Overall, 320 111 patients with stroke had normal albumin levels (70.9±14.7 years; 48.9% females) and 183 729 (57.4%) had reduced albumin levels (72.9±14.3 years; 50.3% females). After propensity score matching, the primary outcomes occurred in 36.0% of patients with reduced and 26.1% with normal albumin levels (HR, 1.48 [95% CI, 1.46-1.50]). The higher risk in patients with reduced albumin levels was consistent also for all-cause death (HR, 2.77 [95% CI, 2.70-2.84]), heart failure (HR, 1.31 [95% CI, 1.29-1.34]), atrial fibrillation (HR, 1.11 [95% CI, 1.09-1.13]), ventricular arrhythmias (HR, 1.38 [95% CI, 1.30-1.46]), myocardial infarction (HR, 1.60 [95% CI, 1.54-1.65]), and Takotsubo cardiomyopathy (HR, 1.51 [95% CI, 1.26-1.82]). The association between albumin levels and the risk of cardiovascular events was independent of advanced age, sex, multimorbidity, and other causes of hypoalbuminemia. A progressively increased risk of adverse events was found in patients with mild and severe reduced compared to normal albumin levels., Conclusions: Albumin levels are associated with the risk of early cardiovascular events and death in patients with ischemic stroke. The potential pathophysiological or therapeutic roles of albumin in patients with stroke warrant further investigation., Competing Interests: Disclosures Dr Lip is a consultant and speaker for Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Anthos and Daiichi-Sankyo. No fees are received personally. Dr Lip is co-principal investigator of the AFFIRMO project (Atrial Fibrillation Integrated Approach in Frail, Multimorbid and Polymedicated Older People) on multimorbidity in atrial fibrillation, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 899871. The other authors report no conflicts.

Background and Purpose: Epilepsy is associated with higher morbidity and mortality compared to people without epilepsy. We performed a retrospective cross-sectional and longitudinal cohort study to evaluate cardiovascular comorbidity and incident vascular events in people with epilepsy (PWE)., Methods: Data were extracted from the French Hospital National Database. PWE (n = 682,349) who were hospitalized between January 2014 and December 2022 were matched on age, sex, and year of hospitalization with 682,349 patients without epilepsy. Follow-up was conducted from the date of first hospitalization with epilepsy until the date of each outcome or date of last news in the absence of the outcome. Primary outcome was the incidence of all-cause death, cardiovascular death, myocardial infarction, hospitalization for heart failure, ischaemic stroke (IS), new onset atrial fibrillation, sustained ventricular tachycardia or fibrillation (VT/VF), and cardiac arrest., Results: A diagnosis of epilepsy was associated with higher numbers of cardiovascular risk factors and adverse cardiovascular events compared to controls. People with epilepsy had a higher incidence of all-cause death (incidence rate ratio [IRR] = 2.69, 95% confidence interval [CI] = 2.67-2.72), cardiovascular death (IRR = 2.16, 95% CI = 2.11-2.20), heart failure (IRR = 1.26, 95% CI = 1.25-1.28), IS (IRR = 2.08, 95% CI = 2.04-2.13), VT/VF (IRR = 1.10, 95% CI = 1.04-1.16), and cardiac arrest (IRR = 2.12, 95% CI = 2.04-2.20). When accounting for all-cause death as a competing risk, subdistribution hazard ratios for ischaemic stroke of 1.59 (95% CI = 1.55-1.63) and for cardiac arrest of 1.73 (95% CI = 1.58-1.89) demonstrated higher risk in PWE., Conclusions: The prevalence and incident rates of cardiovascular outcomes were significantly higher in PWE. Targeting cardiovascular health could help reduce excess morbidity and mortality in PWE., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Systemic chronic inflammation plays a role in the pathophysiology of both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated fatty liver disease. This study aimed to investigate whether serum hs-CRP (high-sensitivity C-reactive protein) levels were associated with the future risk of heart failure (HF) hospitalization in patients with metabolic dysfunction-associated fatty liver disease and a normal left ventricular ejection fraction., Methods and Results: The study enrolled consecutive individuals with metabolic dysfunction-associated fatty liver disease and normal left ventricular ejection fraction who underwent coronary angiography for suspected coronary heart disease. The study population was subdivided into non-HF, pre-HFpEF, and HFpEF groups at baseline. The study outcome was time to the first hospitalization for HF. In 10 019 middle-aged individuals (mean age, 63.3±10.6 years; 38.5% women), the prevalence rates of HFpEF and pre-HFpEF were 34.2% and 34.5%, with a median serum hs-CRP level of 4.5 mg/L (interquartile range, 1.9-10 mg/L) and 5.0 mg/L (interquartile range, 2.1-10.1 mg/L), respectively. Serum hs-CRP levels were significantly higher in the pre-HFpEF and HFpEF groups than in the non-HF group. HF hospitalizations occurred in 1942 (19.4%) patients over a median of 3.2 years, with rates of 3.7% in non-HF, 20.8% in pre-HFpEF, and 32.1% in HFpEF, respectively. Cox regression analyses showed that patients in the highest hs-CRP quartile had a ≈4.5-fold increased risk of being hospitalized for HF compared with those in the lowest hs-CRP quartile (adjusted-hazard ratio, 4.42 [95% CI, 3.72-5.25])., Conclusions: There was a high prevalence of baseline pre-HFpEF and HFpEF in patients with metabolic dysfunction-associated fatty liver disease and suspected coronary heart disease. There was an increased risk of HF hospitalization in those with elevated hs-CRP levels.

We aimed to investigate the relationship between time in target range of systolic blood pressure (SBP-TTr) and clinical outcomes in patients with atrial fibrillation (AF). We analyzed the results from multicenter AF registry in Thailand. Blood pressure was recorded at baseline and at every 6 monthly follow-up visit. SBP-TTr were calculated using the Rosendaal method, based on a target SBP 120-140 mmHg. The outcomes were death, ischemic stroke/systemic embolism (SSE), major bleeding, and heart failure. A total of 3355 patients were studied (mean age 67.8 years; 41.9% female). Average follow-up time was 32.1 ± 8.3 months. SBP-TTr was classified into 3 groups according to the tertiles. The incidence rates of all-cause death, SSE, major bleeding, and heart failure were 3.90 (3.51-4.34), 1.52 (1.27-1.80), 2.2 (1.90-2.53), and 2.83 (2.49-3.21) per 100 person-years, respectively. Patients in the 3rd tertile of SBP-TTr had lower rates of death, major bleeding and heart failure with adjusted hazard ratios 0.62 (0.48-0.80), p < 0.001, 0.64 (0.44-0.92), p = 0.016, and 0.61 (0.44-0.84), p = 0.003, respectively, compared to 1st SBP-TTr tertile. In conclusion, high SBP-TTr was associated with better clinical outcomes compared to other groups with lower SBP-TTr. This underscores the importance of good blood pressure control in AF patients., (© 2024. The Author(s).)

Background: Whether statin use can reduce the risk of heart failure (HF) remains controversial. The present study evaluates the association between statin use and HF in patients with atrial fibrillation., Methods and Results: Patients with newly diagnosed atrial fibrillation from 2010 to 2018 were included. An inverse probability of treatment weighting was used to balance baseline covariates between statin users (n=23 239) and statin nonusers (n=29 251). The primary outcome was incident HF. Cox proportional hazard models with competing risk regression were used to evaluate the risk of HF between statin users and nonusers. The median age of the cohort was 74.7 years, and 47.3% were women. Over a median follow-up of 5.1 years, incident HF occurred in 3673 (15.8%) statin users and 5595 (19.1%) statin nonusers. Statin use was associated with a 19% lower risk of HF (adjusted subdistribution hazard ratio, 0.81 [95% CI, 0.78-0.85]). Restricted to the statin users, duration of statin use was measured during follow-up; compared with short-term use (3 months to <2 years), there was a stepwise reduction in the risk of incident HF among those with 2 to <4 years of statin use (subdistribution hazard ratio, 0.86 [95% CI, 0.84-0.88]), 4 to <6 years of statin use (subdistribution hazard ratio, 0.74 [95% CI, 0.72-0.76]), and ≥6 years of statin use (subdistribution hazard ratio, 0.71 [95% CI, 0.69-0.74]). Subgroup analysis showed consistent reductions in the risk of HF with statin use., Conclusions: Statin use was associated with a decreased risk of incident HF in a duration-dependent manner among patients with atrial fibrillation.

Purpose: Suboptimal glucose control early in the diagnosis of type 2 diabetes (T2D) is strongly associated with subsequent morbidity and mortality, termed the 'glycaemic legacy'. Additionally, it is known that Asian and Black individuals are at increased risk of T2D, and its associated complications compared to their White counterparts. However, ethnicity does not currently feature in the treatment algorithm of T2D, unlike in other cardiovascular disease states such as hypertension. We therefore sought to evaluate the real-world impact of early intensive treatment with combination therapy on cardiorenal outcomes compared to standard treatment in T2D, with a focus on ethnicity., Methods: We performed a retrospective cohort study of all patients aged 18 or over with T2D using the TriNetX platform. TriNetX is a global collaborative network providing access to real time, anonymised medical records. We included patients who were initiated with Metformin and an SGLT2i within one month of diagnosis of T2D and compared this cohort with individuals who received Metformin only for a period of at least 1 year. We evaluated cardiovascular and renal outcomes at three years and stratified by ethnicity. We excluded individuals with a personal history of an outcome of interest., Findings: We identified 49,651 individuals with T2D who were treated with Metformin and an SGLT2i and 1,028,806 patients with T2D who were treated with Metformin alone. A total of 98,094 individuals were included in the core analysis. The Metformin only group had a greater risk of mortality (RR 1.44, [95% CI 1.34-1.55], P<0.0001), CKD (RR 1.10, [95% CI 1.04-1.16], P = 0.0004), diabetic nephropathy (RR 1.06, [95% CI 1.01-1.12], P = 0.0239), heart failure (RR 1.13, [95% CI 1.07-1.21], P < 0.0001) and hospitalisation (RR 1.24, [95% CI 1.21-1.27], P < 0.0001) compared to individuals treated with Metformin and SGLT2i. Black individuals had a reduced risk of mortality (RR 0.71, [95% CI 0.55-0.92], P = 0.0099) and IHD (RR 0.73, [95% CI 0.64-0.84], P < 0.0001) compared to White individuals. Asian individuals had a reduced risk of heart failure (RR 0.61, [95% CI 0.41-0.91], P = 0.0134) and hospitalisation (RR 0.76, [95% CI 0.66-0.87], P = 0.0001) compared to White individuals., Implications: Initial combination treatment within the first year of T2D diagnosis confers favourable cardio-metabolic outcomes when compared to standard therapy, even in patients without established cardiovascular disease. Black and Asian individuals in particular demonstrate a greater degree of benefit compared to White individuals. Further prospective studies with a focus on ethnicity are now required to validate these findings., Competing Interests: Declaration of Competing Interest Mr Austin and Dr Hernández Ibarburu are employees of TriNetX LLC. Dr Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Anthem (no fees are received personally); he is co-principal investigator of the AFFIRMO (Atrial Fibrillation Integrated Approach in Frail, Multimorbid and Polymedicated Older People) project on multimorbidity in atrial fibrillation, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 899871. Dr Alam has received honoraria from Procter & Gamble, Viatris, Grunenthal, and Sanofi for educational meetings; and has received investigator-led funding by Procter & Gamble. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Heart failure (HF) is a major disease in our society that often presents with multiple comorbidities with mutual interaction and aggravation. The comorbidity of HF and stroke is a high risk condition that requires particular attention to ensure early detection of complications, efficient diagnostic workup, close monitoring, and consequent treatment of the patient. The bi-directional interaction between the heart and the brain is inherent in the pathophysiology of HF where HF may be causal for acute cerebral injury, and - in turn - acute cerebral injury may induce or aggravate HF via imbalanced neural and neurovegetative control of cardiovascular regulation. The present document represents the consensus view of the ESC Council on Stroke, the Heart Failure Association and the ESC Working Group on Thrombosis to summarize current insights on pathophysiological interactions of the heart and the brain in the comorbidity of HF and stroke. Principal aspects of diagnostic workup, pathophysiological mechanisms, complications, clinical management in acute conditions and in long-term care of patients with the comorbidity are presented and state-of-the-art clinical management and current evidence from clinical trials is discussed. Beside the physicians perspective, also the patients values and preferences are taken into account. Interdisciplinary cooperation of cardiologists, stroke specialists, other specialists and primary care physicians is pivotal to ensure optimal treatment in acute events and in continued long-term treatment of these patients. Key consensus statements are presented in a concise overview on mechanistic insights, diagnostic workup, prevention and treatment to inform clinical acute and continued care of patients with the comorbidity of HF and stroke., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Diabetes mellitus (DM), heart failure (HF) and metabolic dysfunction associated steatotic liver disease (MASLD) are overlapping diseases of increasing prevalence. Because there are still high numbers of patients with HF who are undiagnosed and untreated, there is a need for improving efforts to better identify HF in patients with DM with or without MASLD. This study aims to develop machine learning (ML) models for assessing the risk of the HF occurrence in patients with DM with and without MASLD., Research Design and Methods: In the Silesia Diabetes-Heart Project (NCT05626413), patients with DM with and without MASLD were analyzed to identify the most important HF risk factors with the use of a ML approach. The multiple logistic regression (MLR) classifier exploiting the most discriminative patient's parameters selected by the χ2 test following the Monte Carlo strategy was implemented. The classification capabilities of the ML models were quantified using sensitivity, specificity, and the percentage of correctly classified (CC) high- and low-risk patients., Results: We studied 2000 patients with DM (mean age 58.85 ± SD 17.37 years; 48% women). In the feature selection process, we identified 5 parameters: age, type of DM, atrial fibrillation (AF), hyperuricemia and estimated glomerular filtration rate (eGFR). In the case of MASLD( +) patients, the same criterion was met by 3 features: AF, hyperuricemia and eGFR, and for MASLD(-) patients, by 2 features: age and eGFR. Amongst all patients, sensitivity and specificity were 0.81 and 0.70, respectively, with the area under the receiver operating curve (AUC) of 0.84 (95% CI 0.82-0.86)., Conclusion: A ML approach demonstrated high performance in identifying HF in patients with DM independently of their MASLD status, as well as both in patients with and without MASLD based on easy-to-obtain patient parameters., (© 2023. The Author(s).)

Background: Atrial fibrillation (AF) has consistently been associated with a higher risk of incident dementia. Observational evidence has suggested catheter ablation may be associated with a lower risk of dementia in patients with AF, but further research is needed. The objectives of this study were to use a global health research network to examine associations between catheter ablation, incident dementia and mortality in older adults with AF, and amongst subgroups by age, sex, co-morbidity status, and oral anticoagulant use., Methods: The research network primarily included healthcare organizations in the United States. This network was searched on 28th September 2022 for patients aged ≥65 years with a diagnosis of AF received at least 5 years prior to the search date. Cox proportional hazard models were run on propensity-score matched cohorts., Results: After propensity score matching, 20,746 participants (mean age 68 years; 59% male) were included in each cohort with and without catheter ablation. The cohorts were well balanced for age, sex, ethnicity, co-morbidities, and cardiovascular medications received. The risk of dementia was significantly lower in the catheter ablation cohort (Hazard Ratio 0.52, 95% confidence interval: 0.45-0.61). The catheter ablation cohort also had a lower risk of all-cause mortality (Hazard Ratio 0.58, 95% confidence interval: 0.55-0.61). These associations remained in subgroup analyses in individuals aged 65-79 years, ≥80 years, males, females, participants who received OACs during follow-up, participants with paroxysmal and non-paroxysmal AF, and participants with and without hypertension, diabetes mellitus, ischemic stroke, chronic kidney disease and heart failure, including heart failure with preserved ejection fraction and heart failure with reduced ejection fraction., Conclusion: The observed lower risk of dementia and mortality with catheter ablation could be an important consideration when determining appropriate patient-centered rhythm control strategies for patients with AF. Further studies including data on the success of ablation are required., (© 2023 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: Atrial fibrillation and heart failure commonly coexist due to shared pathophysiological mechanisms. Prompt identification of patients with heart failure at risk of developing atrial fibrillation would allow clinicians the opportunity to implement appropriate monitoring strategy and timely treatment, reducing the impact of atrial fibrillation on patients' health., Methods: Four machine learning models combined with logistic regression and cluster analysis were applied post hoc to patient-level data from the Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm (WARCEF) trial to identify factors that predict development of atrial fibrillation in patients with heart failure., Results: Logistic regression showed that White divorced patients have a 1.75-fold higher risk of atrial fibrillation than White patients reporting other marital statuses. By contrast, similar analysis suggests that non-White patients who live alone have a 2.58-fold higher risk than those not living alone. Machine learning analysis also identified "marital status" and "live alone" as relevant predictors of atrial fibrillation. Apart from previously well-recognized factors, the machine learning algorithms and cluster analysis identified 2 distinct clusters, namely White and non-White ethnicities. This should serve as a reminder of the impact of social factors on health., Conclusion: The use of machine learning can prove useful in identifying novel cardiac risk factors. Our analysis has shown that "social factors," such as living alone, may disproportionately increase the risk of atrial fibrillation in the under-represented non-White patient group with heart failure, highlighting the need for more studies focusing on stratification of multiracial cohorts to better uncover the heterogeneity of atrial fibrillation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little focus has been placed on the prevention of HF in patients with AF. Left ventricular ejection fraction (LVEF) is an established echocardiographic parameter in HF patients. We sought to investigate the association of LVEF with HF events in AF patients without pre-existing HF., Methods and Results: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Japan. In this analysis, we excluded patients with pre-existing HF (defined as having one of the following: prior HF hospitalization, New York Heart Association class ≥ 2 in association with heart disease, or LVEF < 40%). Among 3233 AF patients without pre-existing HF, we investigated 2459 patients with the data of LVEF at enrolment. We divided the patients into three groups stratified by LVEF [mildly reduced LVEF (40-49%), below normal LVEF (50-59%), and normal LVEF (≥60%)] and compared the backgrounds and incidence of HF hospitalization between the groups. Of 2459 patients [mean age: 72.4 ± 10.5 years, female: 917 (37%), paroxysmal AF: 1405 (57%), and mean CHA 2 DS 2 -VASc score: 3.0 ± 1.6], the mean LVEF was 66 ± 8% [mildly reduced LVEF: 114 patients (5%), below normal LVEF: 300 patients (12%), and normal LVEF: 2045 patients (83%)]. Patients with lower LVEF demonstrated lower prevalence of female and paroxysmal AF (both P < 0.01), but age and CHA 2 DS 2 -VASc score were comparable between the three groups (both P > 0.05). During the median follow-up period of 6.0 years, 255 patients (10%) were hospitalized for HF (annual incidence: 1.9% per person-year). Multivariable Cox regression analysis demonstrated that lower LVEF strata were independently associated with the risk of HF [mildly reduced LVEF (40-49%): hazard ratio = 2.98, 95% confidence interval = 1.99-4.45 and below normal LVEF (50-59%): hazard ratio = 2.01, 95% confidence interval = 1.44-2.82, compared with normal LVEF (≥60%)] after adjustment by age, sex, type of AF, and CHA 2 DS 2 -VASc score. LVEF < 60% was significantly associated with the higher risk of HF hospitalization across all major subgroups without significant interaction (P for interaction; all P > 0.05). LVEF had an independent and incremental prognostic value for HF hospitalization in addition to natriuretic peptide levels in AF patients without pre-existing HF., Conclusions: Lower LVEF was significantly associated with the higher incidence of HF hospitalization in AF patients without pre-existing HF, leading to the future risk stratification for and prevention of incident HF in AF patients., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The risks of cardiovascular events (CVEs) in people with epilepsy (PWE) are not well understood. To establish the short- and long-term burden of CVEs in PWE. Electronic health records from a global federated health research network (TriNetX) were used to establish a cohort of PWE. Primary outcomes were: (1) the proportion of people experiencing a composite outcome of cardiac arrest, acute heart failure (HF), acute coronary syndrome (ACS), atrial fibrillation (AF), severe ventricular arrhythmia or all-cause death within 30 days of a seizure; and (2) the 5-year risk for a composite outcome of ischemic heart diseases, stroke, hospitalization, or all-cause death in the PWE experiencing early CVEs. Cox-regression analyses with propensity score matching was used to produce hazard ratios (HRs) and 95% confidence intervals (CI). In 271,172 PWE (mean age 50 ± 20 years; 52% females), the 30-day risk of CVEs following seizure was: 8.7% for the composite outcome, 0.9% for cardiac arrest, 0.8% for HF, 1.2% for ACS, 4.1% for AF, 0.7% for severe ventricular arrhythmias, and 1.6% for all-cause death. For the 15,120 PWE experiencing CVEs within 30 days of seizure, the 5-year adjusted risks for all composite outcomes measured were significantly increased (overall HR: 2.44, 95% CI 2.37-2.51), ischemic heart diseases HR 3.23 (95% CI 3.10-3.36), stroke HR 1.56 (95% CI 1.48-1.64), hospitalization HR 2.03 (95% CI 1.97-2.10), and all-cause death HR 2.75 (95% CI 2.61-2.89). The large proportions of PWE with active disease that experience CVEs and the poor long-term outcome associated suggest the existence of an "epilepsy-heart syndrome.", Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gregory Y.H. Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. All other authors report no disclosures., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: There are no nationwide epidemiological data on heart failure (HF) stages in China. Knowledge of the prevalence of HF stages is crucial for planning HF prevention and management strategies. We aimed to evaluate the prevalence of HF stages in the general Chinese population and the specific prevalence by age, sex, and urbanity., Methods and Results: This is a cross-sectional study and national representative general population aged ≥ 35 years (n = 31 494, mean age 57.4 years, women 54.1%) were obtained from the China Hypertension Survey. Participants were divided into Stage A (at-risk for HF), Stage B (pre-HF), and Stage C (symptomatic HF). Survey weights were calculated based on the 2010 China population census data. The prevalence of Stage A was 35.8% (≈245.1 million), Stage B 42.8% (≈293.1 million), and Stage C 1.1% (≈7.5 million). The prevalence of Stages B and C increased with increasing age (P < 0.0001). Women had lower prevalence of Stage A (32.6% vs. 39.3%; P < 0.0001) but higher prevalence of Stage B (45.9% vs. 39.5%; P < 0.0001) than men. People from rural area had lower prevalence of Stage A (31.9% vs. 41.0%; P < 0.0001) but higher prevalence of Stage B (47.8% vs. 36.2%; P < 0.0001) than people from urban. The prevalence of Stage C was similar by sex and urbanity., Conclusion: The burdens of pre-clinical and clinical HF are high and vary by age, sex, and urbanity in China. Targeted interventions are needed to reduce the high burden of pre-clinical and clinical HF., Competing Interests: Conflict of interests: Dr Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Janssen, Medtronic, Merck, and Novartis. The other authors declare that they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background:  Visit-to-visit heart rate variability (VVV-HR) has been associated with adverse cardiovascular outcomes. We aimed to determine the predictive value of VVV-HR for adverse clinical outcomes in patients with nonvalvular atrial fibrillation (AF)., Methods:  We used data from a prospective multicenter AF registry of 27 hospitals in Thailand during 2014 to 2017. After the baseline visit, patients were followed up every 6 months until 3 years. VVV-HR was calculated from the standard deviation of heart rate data from baseline visit and every follow-up visit. VVV-HR was categorized into four groups according to the quartiles. Clinical outcomes were all-cause death, ischemic stroke/systemic embolism (SE), and heart failure. Cox proportional hazard models were used for multivariable analysis., Results:  There were a total of 3,174 patients (mean age: 67.7 years; 41.8% female). The incidence rates of all-cause death, ischemic stroke/SE, and heart failure were 3.10 (2.74-3.49), 1.42 (1.18-1.69), and 2.09 (1.80-2.42) per 100 person-years respectively. The average heart rate was 77.8 ± 11.0 bpm and the average of standard deviation of heart rate was 11.0 ± 5.9 bpm. VVV-HR Q4 was an independent predictor of all-cause death, ischemic stroke/SE, and heart failure with adjusted hazard ratios of 1.45 (95% confidence interval: 1.07-1.98), 2.02 (1.24-3.29), and 2.63 (1.75-3.96), respectively. VVV-HR still remained a significant predictor of clinical outcomes when analyzed based on coefficient of variation and variability independent of mean., Conclusion:  VVV-HR is an independent predictor for adverse clinical outcomes in patients with AF. A J -curve appearance was demonstrated for the effect of VVV-HR on all-cause death., Competing Interests: G.Y.H.L. received consultant and speaker fees from BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Anthos. No fees are directly received personally. Other authors hereby declare no personal or professional conflicts of interest relating to any aspect of this particular study., (Thieme. All rights reserved.)

Background: Evidence about the association between calculated remnant cholesterol (RC) and risk of heart failure (HF) in participants with diabetes mellitus (DM) remains sparse and limited., Methods: We included a total of 22 230 participants with DM from the UK Biobank for analyses. Participants were categorized into three groups based on their baseline RC measures: low (with a mean RC of 0.41 mmol/L), moderate (0.66 mmol/L), and high (1.04 mmol/L). Cox proportional hazards models were used to evaluate the relationship between RC groups and HF risk. We performed discordance analysis to evaluate whether RC was associated with HF risk independently of low-density lipoprotein cholesterol (LDL-C)., Results: During a mean follow-up period of 11.5 years, there were a total of 2232 HF events observed. The moderate RC group was significantly related with a 15% increased risk of HF when compared with low RC group (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.01-1.32), while the high RC group with a 23% higher HF risk (HR = 1.23, 95% CI: 1.05-1.43). There was significant relationship between RC as a continuous measure and the increased HF risk (P < 0.01). The association between RC and risk of HF was stronger in participants with HbA1c level ≥ 53 mmol/mol when compared with HbA1c < 53 mmol/mol (P for interaction = 0.02). Results from discordance analyses showed that RC was significantly related to HF risk independent of LDL-C measures., Conclusions: Elevated RC was significantly associated with risk of HF in patients with DM. Moreover, RC was significantly related to HF risk independent of LDL-C measures. These findings may highlight the importance of RC management to HF risk in patients with DM., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To evaluate the association between regular glucosamine intake and heart failure (HF) and to explore whether the association is mediated by relevant cardiovascular disease., Patients and Methods: We included 479,650 participants with data available for supplement use and without HF at baseline from the UK Biobank study. Using 12 single-nucleotide polymorphisms linked to HF, a weighted genetic risk score was calculated. We evaluated the association between glucosamine use and HF by Cox regression models after inverse probability of treatment weighting. A validation and mediation analysis were performed through two-sample Mendelian randomization. The study was from May 18, 2006, to February 16, 2018., Results: During a median follow-up of 9.0 (IQR, 8.3-9.8) years, we documented 5501 incident cases of HF. In multivariable analysis, the HR of glucosamine users for HF was 0.87 (95% CI, 0.81 to 0.94). The inverse associations were stronger in males and participants with unfavorable lifestyle (P<.05 for interaction). Genetic risk categories did not modify this association (P>.05 for interaction). Multivariable Mendelian randomization showed that taking glucosamine was protective against HF (HR, 0.92; 95% CI, 0.87 to 0.96). The mediated proportion of coronary heart disease and stroke were 10.5% (95% CI, 7.6% to 13.4%) and 14.4% (95% CI, 10.8% to 18.0%), respectively. The two-mediator combination accounted for 22.7% (95% CI, 17.2% to 28.2%) of the effect of glucosamine use., Conclusion: Regular glucosamine supplementation was associated with a lower risk of HF regardless of genetic risk status, and to a lesser extent, coronary heart disease and stroke mediated this effect. The results may inform novel pathway for prevention and intervention toward HF., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The role of inflammation in predicting early cardiac complications among stroke patients is unclear. Electronic medical records from TriNetX, a global federated health research network, were used for this retrospective analysis. Patients with ischemic stroke and C-Reactive Protein (CRP) levels measured within 24 h post-stroke were categorized into three groups: (i) < 1 mg/L, (ii)1-3 mg/L and (iii) > 3 mg/L. The primary outcome was a composite outcome of cardiac complications (heart failure (HF), ischemic heart disease, atrial fibrillation (AF), ventricular arrhythmias and Takotsubo cardiomyopathy) or death at 30 days from the index event. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Of the 104,741 patients enrolled, 51% were female and the mean age was 66 ± 16 years. After PSM, a new cardiac complication or death within 30 days occurred in 5624 (33.1%) patients with CRP > 3 mg/L, in 4243 (25.6%) patients with CRP 1-3 mg/L and in 3891 (23.5%) patients with CRP < 1 mg/L. Patients with CRP levels of 1-3 mg/L and > 3 mg/L had higher risk of the composite outcome (HR 1.10, 95%CI 1.05-1.52; HR 1.51, 95%CI 1.45-1.58), death (HR 1.43, 95%CI 1.24-1.64; HR 3.50, 95%CI 3.01-3.96), HF (HR 1.08, 95%CI 1.01-1.16; HR 1.51, 95%CI 1.41-1.61), AF (HR 1.10, 95% CI:1.02-1.18; HR 1.42, 95%CI 1.33-1.52) and ventricular arrhythmias (HR 1.25, 95%CI 1.02-1.52; HR 1.67, 95% CI 1.38-2.01) compared to those with CRP < 1 mg/L. Ischemic heart disease were more common among patients with CRP levels > 3 mg/L compared to those with CRP < 1 mg/L (HR:1.33, 95% CI:1.26-1.40), while no association with Takotsubo cardiomyopathy was found in all the analyses. CRP levels within the first 24 h of an ischemic stroke predict 30-day cardiac complications or death., (© 2023. The Author(s).)

Aims: We aim to evaluate the association of frailty and high body mass index with risk of incident heart failure., Methods and Results: From the Kuopio Ischaemic Heart Disease Risk Factor Study, 408 women and 369 men, aged 61-74 years were included in this study. Frailty was ascertained with the presence of 3-5 and prefrailty 1-2 of the following criteria: weight loss (highest 20% over 7 years), self-reported tiredness, weakness (measured by handgrip strength), slow walking speed (walking pace), and low physical activity (lowest 20%). At the baseline, participants were allocated to frail (n = 36), prefrail (n = 340), and robust (n = 441). HF incidents were obtained by record linkages from the national hospitalization registry in Finland up to 31 December 2019. Multivariate Cox proportional hazards regression estimated the hazard ratio (HR) of incident events, adjusted for potential confounders. Two hundred one HF events were recorded (111 in women and 90 in men) during the 14.2 years follow-up. After adjustment for the age and sex, the risk of HF events was higher among prefrail (HR 1.42, 95% CI 1.08 to 1.79, P = 0.02) and frail (HR 3.39, 95% CI 1.89 to 4.79, P ≤ 0.001) compared with the robust group. After adjusting for multiple confounders result remained significant for HF indecent in prefrail [1.46 (HR 1.46, 95% CI 1.09 to 1.95, P = 0.01] and frail (HR 3.33, 95% CI 1.86 to 5.70, P ≤ 0.001). In the sensitivity analysis, significant interaction between high BMI (≥25 kg/m 2 ) and frailty was observed (P for interaction = 0.02). The association of frailty [multivariate-adjusted HR: 2.88 (1.56 to 5.33), P ≤ 0.001)] and prefrailty [multivariate-adjusted HR: 1.40 (1.08 to 1.91), P = 0.03)] with risk of HF indecent was more pronounced in those with high BMI., Conclusions: Frailty is highly common in older age, and our results indicated the high risk of HF incident in frail and prefrail groups. While frailty is clinically recognized by weight loss phenotype, our finding showed that frailly and high BMI can coexist and worsen the risk of HF incidence. Further research is warranted to substantiate these results in large studies and clinical settings., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Heart failure is a complex, debilitating condition and despite advances in treatment, it remains a significant cause of morbidity and mortality worldwide. Therefore, the need for alternative treatment strategies is essential. In this review, we explore the therapeutic strategies of augmenting natriuretic peptide receptors (NPR-A and NPR-B) and cyclic guanosine monophosphate (cGMP) in heart failure., Areas Covered: We aim to provide an overview of the evidence of preclinical and clinical studies on novel heart failure treatment strategies. Papers collected in this review have been filtered and screened following PubMed searches. This includes epigenetics, modulating enzyme activity in natriuretic peptide (NP) synthesis, gene therapy, modulation of downstream signaling by augmenting soluble guanylate cyclase (sGC) and phosphodiesterase (PDE) inhibition, nitrates, c-GMP-dependent protein kinase, synthetic and designer NP and RNA therapy., Expert Opinion: The novel treatment strategies mentioned above have shown great potential, however, large randomized controlled trials are still lacking. The biggest challenge is translating the results seen in preclinical trials into clinical trials. We recommend a multi-disciplinary team approach with cardiologists, geneticist, pharmacologists, bioengineers, researchers, regulators, and patients to improve heart failure outcomes. Future management can involve telemedicine, remote monitoring, and artificial intelligence to optimize patient care.

We aimed to develop a machine learning (ML) model for predicting cardiovascular (CV) events in patients with diabetes (DM). This was a prospective, observational study where clinical data of patients with diabetes hospitalized in the diabetology center in Poland (years 2015-2020) were analyzed using ML. The occurrence of new CV events following discharge was collected in the follow-up time for up to 5 years and 9 months. An end-to-end ML technique which exploits the neighborhood component analysis for elaborating discriminative predictors, followed by a hybrid sampling/boosting classification algorithm, multiple logistic regression (MLR), or unsupervised hierarchical clustering was proposed. In 1735 patients with diabetes (53% female), there were 150 (8.65%) ones with a new CV event in the follow-up. Twelve most discriminative patients' parameters included coronary artery disease, heart failure, peripheral artery disease, stroke, diabetic foot disease, chronic kidney disease, eosinophil count, serum potassium level, and being treated with clopidogrel, heparin, proton pump inhibitor, and loop diuretic. Utilizing those variables resulted in the area under the receiver operating characteristic curve (AUC) ranging from 0.62 (95% Confidence Interval [CI] 0.56-0.68, P < 0.01) to 0.72 (95% CI 0.66-0.77, P < 0.01) across 5 nonoverlapping test folds, whereas MLR correctly determined 111/150 (74.00%) high-risk patients, and 989/1585 (62.40%) low-risk patients, resulting in 1100/1735 (63.40%) correctly classified patients (AUC: 0.72, 95% CI 0.66-0.77). ML algorithms can identify patients with diabetes at a high risk of new CV events based on a small number of interpretable and easy-to-obtain patients' parameters., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Heart failure (HF) is a major public health issue associated with significantly increased risk of stroke. It remains uncertain whether oral anticoagulation (OAC) in patients with heart failure and sinus rhythm (HF-SR) could improve prognosis., Methods: We performed a systematic search of PubMed and Embase databases for randomized controlled clinical trials assessing oral anticoagulants versus antiplatelets or placebo in patients with HF or ventricular dysfunction/cardiomyopathy without clinical HF and SR. The outcomes assessed were stroke/systemic embolism, major bleeding, myocardial infarction, all-cause mortality, and HF hospitalization., Results: Seven trials of 15,794 patients were eligible for our analyses. The overall follow-up duration was 32,367 patient-years corresponding to a mean follow-up of 2.05 years per patient. Four trials included patients treated with warfarin and three included patients treated with rivaroxaban. OAC was associated with reduced rate of stroke or systemic embolism compared to control (odds ratio (OR): 0.57, 95% confidence interval (CI): 0.44, 0.73, number needed to treat (NNT): 71.9) but higher rate of major bleeding (OR: 1.92, 95% CI: 1.47, 2.50, number needed to harm (NNH): 57.1). In the subgroup analysis according to the type of OAC, rivaroxaban was associated with significantly reduced rate of stroke or systemic embolism (1.24 vs 1.97 events per 100 patient-years, respectively, OR: 0.63, 95% CI: 0.45, 0.88, NNT: 82) and higher risk of major bleeding (OR: 1.66, 95% CI: 1.26, 2.20) compared to antiplatelets or placebo. There was no significant differences between groups for the outcomes of myocardial infarction, all-cause mortality, and HF hospitalization., Conclusion: This analysis shows that any benefit of OAC for stroke prevention may be offset by an increased risk of major bleeding in HF-SR patients. A well-designed randomized controlled trial of newer safer OACs is needed in this population.

Aims: Utilizing real-world UK data, we aimed to understand: (i) whether anti-arrhythmic drugs and catheter ablation are effective in improving the survival of atrial fibrillation (AF) patients and (ii) which rhythm control option produces better results for the whole AF population and for specific groups of patients, stratified by age, sex, and history of heart failure., Methods and Results: We identified 199 433 individuals (mean age at diagnosis 75.7 ± 12.7 years; 50.2% women) with new-onset AF diagnosis in nationwide electronic health records linking primary care consultation with hospital data and death registry data from 1998 to 2016. We investigated the survival and causes of death of new-onset AF patients receiving vs. not-receiving rhythm control therapies. During a median follow-up of 2.7 (0.7-6.0) years, we observed a significantly lower mortality in patients receiving rhythm control [multivariate-adjusted hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.84-0.88]. Pulmonary vein isolation was associated with a two-third significant mortality reduction compared with no rhythm control (HR = 0.36, 95% CI 0.28-0.48), flecainide with 50% reduction (HR = 0.52, 95% CI 0.48-0.57), and propafenone and sotalol with reduction by a third (HR = 0.63, 95% CI 0.50-0.81, 0.71, 95% CI 0.68-0.74, respectively). Amiodarone showed no survival benefit in individuals <70 years (HR = 0.99, 95% CI 0.97-1.02). Otherwise, the effect of rhythm control on survival did not differ by age, sex, nor history of heart failure., Conclusion: Among individuals with new-onset AF, favourable survival was observed for patients receiving rhythm control treatment. Among different rhythm control strategies, pulmonary vein isolation showed the most pronounced survival benefit., Competing Interests: Conflict of interest: P.D.L. receives research grants from Medtronic, Abbott, and Boston Scientific; G.Y.H.L. is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally; No other conflicts of interest to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background We aimed to determine the effect of integrating Atrial Fibrillation Better Care pathway compliance in relation to achievement of systolic blood pressure (SBP) targets and good control of time in therapeutic range (TTR) on clinical outcomes in patients with atrial fibrillation. Methods and Results We prospectively enrolled patients with nonvalvular atrial fibrillation  from 27 hospitals in Thailand. All clinical outcomes were recorded. Main outcomes were the composite of all-cause death or ischemic stroke/systemic embolism (SSE), as well as secondary outcomes of all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure. An SBP of 120 to 140 mm Hg was considered good blood pressure control. Target TTR was a TTR ≥65%. A total of 3405 patients were studied (mean age 67.8 years, 41.8% female). Full ABC pathway compliance was evident in 42.7%. For blood pressure control, 41.9% had SBP within target, whereas 35.9% of those on warfarin had TTR within target. The incidence rates of all-cause death/SSE, all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure were 5.29, 4.21, 1.51, 2.25, 0.78, and 2.84 per 100 person-years respectively. Adjusted hazard ratios and 95% CI of Atrial Fibrillation Better Care pathway compliance for all-cause death/SSE, all-cause death, and heart failure were 0.76 (0.62-0.94), 0.79 (0.62-0.99), and 0.69 (0.51-0.94), respectively, compared with noncompliance. Patients with Atrial Fibrillation Better Care compliance and SBP within target had a better outcome or TTR within target had better outcomes. Conclusions In COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Level in Patients With Non-Valvular Atrial Fibrillation in Thailand), a multicenter nationwide prospective cohort of patients with atrial fibrillation, achieving SBP within target and TTR ≥ 65% has added value to Atrial Fibrillation Better Care pathway compliance in the reduction of adverse clinical outcomes in patients with atrial fibrillation.

Aims: This study aimed to determine the impact of heart failure (HF) on clinical outcomes in patients with atrial fibrillation (AF)., Methods and Results: We analysed data from Polish participants of the EURObservational Research Programme-AF General Long-Term Registry. The primary endpoint was all-cause death, and the secondary endpoints included hospital readmissions, cardiovascular (CV) interventions, thromboembolic and haemorrhagic events, rhythm control interventions, and other CV or non-CV diseases development during one-year follow up. Overall, 688 patients with available data on HF were included into analysis; 51% (n = 351) had HF; of these 48% (n = 168) had reduced ejection fraction (HFrEF), 22% (n = 77) mid-range EF (HFmrEF), and 30% (n = 106) preserved EF (HFpEF). Compared with patients without HF, those with HF had higher mortality rate (aHR 5.61; 95% CI 1.94-16.22, P < 0.01). Patients with HF (vs. without HF) had more often CV interventions (10% vs. 5.4%, P = 0.046) and events (14% vs. 7.1%, P = 0.02), and had less often atrial arrhythmia-related hospital admissions (6.8% vs. 15%, P < 0.01). Over follow-up, patients with HFmrEF and HFpEF had similar mortality rate versus HFrEF (aHR 0.45, 95% CI 0.13-1.57, P = 0.45 for HFmrEF and aHR 0.54, 95% CI 0.20-1.48, P = 0.54 for HFpEF). Mortality rate was similar among rhythm versus rate control group (aHR 0.34; 95% CI 0.10-1.16; P = 0.34)., Conclusions: AF patients with HF have greater mortality rate and more CV interventions/events. No statistically significant difference in long-term outcomes between patients with HFrEF, HFmrEF, and HFpEF highlights the need to develop therapeutic strategies targeting functional status and survival for patients with HF and AF., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim: To investigate the impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the risk of incident heart failure and adverse cardiovascular outcomes., Methods: All patients with diabetes who were registered between January 2018 and December 2019 were identified from a federated electronic medical record database (TriNetX) and followed up for 2 years. A 1:1 propensity-score matching (PSM) analysis was performed to balance the SGLT2 inhibitor and non-SGLT2 inhibitor cohorts. The primary outcome was incident heart failure. Secondary outcomes included all-cause mortality, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF), incident atrial fibrillation (AF), ischaemic stroke/transient ischaemic attack (TIA), composite of arterial and venous thrombotic events, and composite of incident VT/VF and cardiac arrest., Results: A total of 131 189 and 2 692 985 patients were treated with and without SGLT2 inhibitors, respectively. After PSM, 131 188 patients remained in each group. The risk of incident heart failure was significantly lower in the SGLT2 inhibitor cohort compared to the non-SGLT2 inhibitor cohort (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.68-0.73). SGLT2 inhibitor use was also associated with a significantly lower risk of all-cause mortality (HR 0.61, 95% CI 0.58-0.64), cardiac arrest (HR 0.70, 95% CI 0.63-0.78), incident AF (HR 0.81, 95% CI 0.76-0.84), ischaemic stroke/TIA (HR 0.90, 95% CI 0.88-0.93), composite of arterial and venous thrombotic events (HR 0.90, 95% CI 0.88-0.92), and composite of incident VT/VF and cardiac arrest (HR 0.76, 95% CI 0.71-0.81). There were no significant differences for VT/VF (HR 0.94, 95% CI 0.88-1.00)., Conclusion: Use of SGLT2 inhibitors was associated with a significant reduction in the risk of incident heart failure and adverse cardiovascular outcomes but not ventricular arrhythmias., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objectives: Accurate prediction of heart failure (HF) patients at high risk of atrial fibrillation (AF) represents a potentially valuable tool to inform shared decision making. No validated prediction model for AF in HF is currently available. The objective was to develop clinical prediction models for 1-year risk of AF., Methods: Using the Danish Heart Failure Registry, we conducted a nationwide registry-based cohort study of all incident HF patients diagnosed from 2008 to 2018 and without history of AF. Administrative data sources provided the predictors. We used a cause-specific Cox regression model framework to predict 1-year risk of AF. Internal validity was examined using temporal validation., Results: The population included 27 947 HF patients (mean age 69 years; 34% female). Clinical experts preselected sex, age at HF, NewYork Heart Association (NYHA) class, hypertension, diabetes mellitus, chronic kidney disease, obstructive sleep apnoea, chronic obstructive pulmonary disease and myocardial infarction. Among patients aged 70 years at HF, the predicted 1-year risk was 9.3% (95% CI 7.1% to 11.8%) for males and 6.4% (95% CI 4.9% to 8.3%) for females given all risk factors and NYHA III/IV, and 7.5% (95% CI 6.7% to 8.4%) and 5.1% (95% CI 4.5% to 5.8%), respectively, given absence of risk factors and NYHA class I. The area under the curve was 65.7% (95% CI 63.9% to 67.5%) and Brier score 7.0% (95% CI 5.2% to 8.9%)., Conclusion: We developed a prediction model for the 1-year risk of AF. Application of the model in routine clinical settings is necessary to determine the possibility of predicting AF risk among patients with HF more accurately and if so, to quantify the clinical effects of implementing the model in practice., Competing Interests: Competing interests: GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. SPJ: Consultant and speaker for BMS/Pfizer. Research grants from BMS/Pfizer and Novo Nordisk. LF: Supported by a grant from Health Research Fund of Central Denmark Region. Consultant for BMS and Pfizer., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background:  Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with increased risks of stroke and other adverse outcomes., Aims:  This study sought to determine whether the Essen Stroke Risk Score (ESRS) could predict the risks of adjudicated clinical outcomes in patients with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial., Methods:  We evaluated associations of baseline ESRS with clinical outcomes by using the Cox proportional hazard model with competing risk regression. The diagnostic accuracy of the ESRS was assessed using the C-index and calibration data., Results:  Of 3,441 HFpEF patients with a mean follow-up of 3.3 years, the risk of stroke ranged from 0.32% per year at an ESRS of 1 to 2 points to 1.71% per year at a score of ≥6 points. Each point increase in ESRS was associated with increased risks of primary composite outcome (hazard ratios [HRs] = 1.31; 95% confidence intervals [CIs]: 1.23-1.40; C-index = 0.68), stroke (HR = 1.33 [95% CI: 1.16-1.53]; C-index = 0.68), myocardial infarction (HR = 1.60 [95% CI: 1.40-1.83]; C-index = 0.75), HF hospitalization (HR = 1.30 [95% CI: 1.20-1.41]; C-index = 0.71), any hospitalization (HR = 1.20, 95% CI: 1.15-1.26; C-index = 0.68), cardiovascular death (HR = 1.32 [95% CI: 1.20-1.44]; C-index = 0.68), and all-cause death (HR = 1.37, [95% CI: 1.28-1.48]; C-index = 0.68). The calibration curves showed that the ESRS had a better agreement between predicted and observed stroke risks compared with the R2CHADS2, CHADS2, or CHA2DS2-VASC stroke scores., Conclusion:  The ESRS had modest discriminatory abilities for predicting stroke as well as other adverse outcomes including myocardial infarction, hospitalization, and death in HFpEF patients. ESRS might have better calibration performance than R2CHADS2, CHADS2, or CHA2DS2-VASC in HFpEF at high risk for stroke., Clinical Trial Registration:  URL: https://clinicaltrials.gov. Unique identifier: NCT00094302., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To evaluate the association between prediabetes and heart failure (HF) and the association of HF with changes in glycemic status., Research Design and Methods: Patients newly diagnosed with atrial fibrillation (AF) between 2015 and 2018 were divided into three groups (normoglycemia, prediabetes, and type 2 diabetes) according to their baseline glycemic status. The primary outcome was incident HF. The Fine and Gray competing risks model was applied, with death defined as the competing event., Results: Among 17,943 patients with AF (mean age 75.5 years, 47% female), 3,711 (20.7%) had prediabetes, and 10,127 (56.4%) had diabetes at baseline. Over a median follow-up of 4.7 years, HF developed in 518 (14%) patients with normoglycemia, 646 (15.7%) with prediabetes, and 1,795 (17.7%) with diabetes. Prediabetes was associated with an increased risk of HF compared with normoglycemia (subdistribution hazard ratio [SHR] 1.12, 95% CI 1.03-1.22). In patients with prediabetes at baseline, 403 (11.1%) progressed to diabetes, and 311 (8.6%) reversed to normoglycemia at 2 years. Compared with remaining prediabetic, progression to diabetes was associated with an increased risk of HF (SHR 1.50, 95% CI 1.13-1.97), whereas reversion to normoglycemia was associated with a decreased risk (SHR 0.61, 95% CI 0.42-0.94)., Conclusions: Prediabetes was associated with an increased risk of HF in patients with AF. Compared with patients who remained prediabetic, those who progressed to diabetes at 2 years experienced an increased risk of HF, whereas those who reversed to normoglycemia incurred a lower risk of HF., (© 2022 by the American Diabetes Association.)

Background:  In the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4), early rhythm control was associated with better clinical outcomes for patients with atrial fibrillation (AF). However, the intervention arm had more structured and regular follow-up, and whether the better outcomes of patients assigned to rhythm control were solely due to "early" intervention or because of more regular and structured follow-up was unclear., Objective:  In the present study, we aimed to investigate whether the findings of the EAST trial are applicable to the "real-world" clinical setting, where a less structured management protocol is operated., Methods:  From 2001 to 2016, 301,064 newly diagnosed AF patients were identified from Taiwan National Health Insurance Research Database. Among these patients, 62,649 AF patients receiving antiarrhythmic drugs or catheter ablation within 1 year after AF being diagnosed (similar to the timing definition of the EAST-AFNET 4 trial) were categorized as the early rhythm control group, and the remaining 238,415 patients were defined as usual care group. Risks of clinical events were compared between the two groups., Results:  Compared with usual care, early rhythm control was associated with a lower adjusted risk of ischemic stroke (adjusted hazard ratio [aHR]: 0.771, 95% confidence interval [CI]: 0.751-0.792; p  < 0.001), heart failure (aHR: 0.851, 95% CI: 0.806-0.899; p  < 0.001), acute myocardial infarction (aHR: 0.915, 95% CI: 0.877-0.955; p  < 0.001), mortality (aHR: 0.794, 95% CI: 0.782-0.806; p  < 0.001), and composite adverse events (aHR: 0.823, 95% CI: 0.813-0.834; p  < 0.001). Compared with usual care, the lower risks of ischemic stroke (aHR: 0.746, 95% CI: 0.717-0.775), heart failure (aHR: 0.819, 95% CI: 0.798-0.841), mortality (aHR: 0.777, 95% CI: 0.759-0.795), and composite adverse events (aHR: 0.802, 95% CI: 0.787-0.818) associated with early rhythm control were even more evident when performed early (<3 months) compared to later periods (3-6 months, 7-9 months, and 10-12 months; p int  < 0.001). Principal results were generally consistent for majority of subgroups studied and among the cohort after propensity matching., Conclusion:  In this nationwide cohort study, early rhythm control therapy was associated with a lower risk of adverse events compared with usual care among patients with early AF. Outcomes were even better with earlier (<3 months) intervention., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: We examined the associations between family income and educational attainment with incident atrial fibrillation (AF), myocardial infarction (MI), stroke and cardiovascular (CV) death among patients with newly-diagnosed heart failure (HF)., Methods: In a nationwide Danish registry of HF patients diagnosed between 2008 and 2018, we established a cohort for each outcome. When examining AF, MI and stroke, respectively, patients with a history of these outcomes at diagnosis of HF were excluded. We used cause-specific proportional hazard models to estimate hazard ratios for tertile groups of family income and three levels of educational attainment., Results: Among 27,947 AF-free patients, we found no association between income or education and incident AF. Among 27,309 MI-free patients, we found that lower income (hazard ratio 1.28 [95% CI 1.11-1.48] and 1.11 [0.96-1.28] for lower and medium vs. higher income) and education (1.23 [1.04-1.45] and 1.15 [0.97-1.36] for lower and medium vs. higher education) were associated with MI. Among 36,801 stroke-free patients, lower income was associated with stroke (1.38 [1.23-1.56] and 1.27 [1.12-1.44] for lower and medium vs. higher income) but not education. Lower income (1.56 [1.46-1.67] and 1.32 [1.23-1.42] for lower and medium vs. higher income) and education (1.20 [1.11-1.29] and 1.07 [0.99-1.15] for lower and medium vs. higher education) were associated with CV death., Conclusions: In patients with newly-diagnosed HF, lower family income was associated with higher rates of acute MI, stroke and cardiovascular death. Lower educational attainment was associated with higher rates of acute MI and cardiovascular death. There was no evidence of associations between income and education with incident AF., (© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Current guidelines recommend rhythm control for improving symptoms and quality of life in symptomatic patients with atrial fibrillation (AF). However, the long-term prognostic outcomes of rhythm control compared with rate control are still inconclusive. In this meta-analysis, we aimed to assess the effects of early rhythm control compared with rate control on clinical outcomes in newly diagnosed AF patients., Methods: We systematically searched the PubMed and Embase databases up to August 2022 for randomized and observational studies reporting the associations of early rhythm control (defined as within 12 months of AF diagnosis) with effectiveness outcomes. The primary outcome was a composite of death, stroke, admission to hospital for heart failure (HF), or acute coronary syndrome (ACS). Hazard ratios (HRs) and 95% confidence intervals (CIs) from each study were pooled using a random-effects model, complemented with an inverse variance heterogeneity or quality effects model., Results: A total of 8 studies involving 447,202 AF patients were included, and 23.5% of participants underwent an early rhythm-control therapy. In the pooled analysis using the random-effects model, compared with rate control, the early rhythm-control strategy was significantly associated with reductions in the primary composite outcome (HR = 0.88, 95% CI: 0.86-0.89) and secondary outcomes, including stroke or systemic embolism (HR = 0.78, 95% CI: 0.71-0.85), ischemic stroke (HR = 0.81, 95% CI: 0.69-0.94), cardiovascular death (HR = 0.83, 95% CI: 0.70-0.99), HF hospitalization (HR = 0.90, 95% CI: 0.88-0.92), and ACS (HR = 0.86, 95% CI: 0.76-0.98). Reanalyses using the inverse variance heterogeneity or quality effects model yielded similar results., Conclusions: Our current meta-analysis suggested that early initiation of rhythm control treatment was associated with improved adverse effectiveness outcomes in patients who had been diagnosed with AF within 1 year., Registration: The study protocol was registered to PROSPERO (CRD42021295405)., (© 2022. The Author(s).)

Aims: Incident atrial fibrillation (AF) is an adverse prognostic indicator in heart failure (HF); identifying modifiable targets may be relevant to reduce the incidence and morbidity of AF. Therefore, we examined the association between quality of HF care and risk of AF., Methods and Results: Using the Danish Heart Failure Registry, we conducted a nationwide registry-based cohort study of all incident HF patients diagnosed between 2008 and 2018 and without history of AF. Quality of HF care was assessed by seven process performance measures, including echocardiographic examination, New York Heart Association classification, treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid antagonists, physical training, and patient education. In the main analysis, we examined adherence with all measures in a cohort of 25 100 patients (mean age 68.5 ± 13.2 years; 33.6% women). The median follow-up was 3.1 years. Cox proportional hazard regressions estimated the hazard ratios (HRs) with 95% confidence intervals (95% CIs) between the number of fulfilled measures and incident AF. In a multivariable-adjusted analysis with 0 fulfilled performance measures as reference, the HRs (95% CIs) were 1: 0.78 (0.61-1.00), 2: 0.63 (0.49-0.80), 3: 0.53 (0.36-0.80), 4: 0.64 (0.44-0.94), 5: 0.56 (0.39-0.82), 6: 0.51 (0.35-0.74), and 7: 0.49 (0.33-0.73), with a significant decreasing linear trend (P < 0.001)., Conclusion: In patients with incident HF, fulfilment of guideline-based process performance measures was associated with decreased long-term risk of AF. This study supports initiatives to improve the quality of care for patients with HF to prevent incident AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Prior studies have reported conflicting results on digoxin's impact on clinical outcomes and quality of life, and there are limited data from Asia. The aim of this study is to evaluate the use of digoxin and its impact on clinical outcomes and quality of life in a high-risk cohort of elderly Chinese atrial fibrillation (AF) patients., Methods and Results: The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry is a prospective, multicentre nationwide study conducted from October 2014 to December 2018. Endpoints of interest were the composite outcome of all-cause death/any thromboembolism (TE), all-cause death, cardiovascular death, sudden cardiac death, and TE events, as well as the quality of life. The eligible cohort for this analysis included 6391 individuals, of whom 751 (11.8%) patients were treated with digoxin. On multivariate analysis, the use of digoxin was associated with a higher odds ratio (OR) of composite outcome [OR: 1.71; 95% confidence interval (CI): 1.32-2.22], all-cause death (OR: 1.62; 95% CI: 1.23-2.14), and any TE (OR: 1.78; 95% CI: 1.08-2.95). Results were consistent in a subgroup of patients with diagnosed heart failure (HF) and patients with permanent AF. The use of digoxin was associated with worse health-related quality of life (mean EQ index: 0.76 ± 0.19 vs. 0.84 ± 0.18; P < 0.001)., Conclusions: In this nationwide cohort study, digoxin use was associated with an overall higher risk of the composite outcome of all-cause death/any TE, all-cause death, and any TE, regardless of HF diagnosis. Patients treated with digoxin had a worse health-related quality of life., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

As the most prevalent form of arrhythmia, atrial fibrillation (AF) increases the risk of heart failure, thromboembolism, and stroke, contributing to the raising mortality and morbidity in patients with cardiovascular diseases. Despite the multifaceted nature of AF pathogenesis and complexity of AF pathophysiology, a growing body of evidence indicates that the NLRP3 inflammasome activation contributes to onset and progression of AF. Herein, the authors aim at reviewing the current literature on the role of inflammasome signaling in AF pathogenesis, and novel therapeutic options in the management of AF., Competing Interests: Funding Support and Author Disclosures Dr Nattel is supported by the Canadian Institutes of Health Research. Dr Lip has been a consultant and speaker for Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo; no fees are received personally. Dr Ren has received support in part from the Natural Science Foundation of China (82130011). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Breast cancer (BC) is one of the most common cancers worldwide, and the treatments are frequently cardiotoxic. Whether BC is associated with a higher risk of cardiovascular events is a matter of debate. We evaluated the associations among BC and incident cardiovascular events in a contemporary population., Methods: All female patients discharged from French hospitals in 2013 with at least 5 years of follow-up and without a history of major adverse cardiovascular event (myocardial infarction [MI], heart failure [HF], ischaemic stroke or all-cause death, and MACE-HF, which includes cardiovascular death, MI, ischaemic stroke or HF) or cancer (except BC) were identified. After propensity score matching, patients with BC were matched 1:1 with patients with no BC. Hazard ratios (HRs) for cardiovascular events during follow-up were adjusted on age, sex and smoking status at baseline., Results: 1,795,759 patients were included, among whom 64,480 (4.3%) had history of BC. During a mean follow-up of 5.1 years, matched female patients with BC had a higher risk of all-cause death (HR 3.55, 95% confidence interval [CI]: 3.47-3.64), new-onset HF (HR 1.08, 95% CI 1.04-1.11), major bleeding (HR 1.43, 95% CI 1.36-1.49), MACE-HF (HR 1.07, 95% CI 1.04-1.11) and net adverse clinical events (NACE) including all-cause death, MI, ischaemic stroke, HF or major bleeding (HR 2.53, 95% CI 2.48-2.58) compared with those with no BC. By contrast, risks were not higher for cardiovascular death (HR 0.94, 95% CI 0.88-1.00) and were lower for MI (HR 0.81, 95% CI 0.75-0.88) and ischaemic stroke (HR 0.85, 95% CI 0.79-1.11)., Conclusions: In a large and contemporary analysis of female patients seen in French hospitals, women with history of breast cancer had a higher risk of all-cause mortality, new-onset heart failure and major bleeding compared to a matched cohort of women without breast cancer. In contrast, they have a reduced risk of cardiovascular mortality, MI and stroke., (© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Aims: Accumulating evidence questions the clinical value of percutaneous coronary intervention (PCI) for patients with chronic coronary syndrome (CCS). We therefore compare the impact of exercise-based cardiac rehabilitation (CR) vs. PCI in patients with CCS on 18-month mortality and morbidity, and evaluate the effects of combining PCI with exercise-based CR., Methods and Results: A retrospective cohort study was conducted in March 2021. An online, real-world dataset of CCS patients was acquired, utilizing TriNetX, a global federated health research network. Patients with CCS who received PCI were first compared with patients who were prescribed exercise-based CR. Second, we compared patients who received both CR + PCI vs. CR alone. For both comparisons, patients were propensity-score matched by age, sex, race, comorbidities, medications, and procedures. We ascertained 18-month incidence of all-cause mortality, rehospitalization, and cardiovascular comorbidity [stroke, acute myocardial infarction (AMI), and new-onset heart failure]. The initial cohort consisted of 18 383 CCS patients. Following propensity score matching, exercise-based CR was associated with significantly lower odds of all-cause mortality [0.37 (95% confidence interval (CI): 0.29-0.47)], rehospitalization [0.29 (95% CI: 0.27-0.32)], and cardiovascular morbidities, compared to PCI. Subsequently, patients that received both CR + PCI did not have significantly different odds for all-cause mortality [1.00 (95% CI: 0.63-1.60)], rehospitalization [1.00 (95% CI: 0.82-1.23)], AMI [1.11 (95% CI: 0.68-1.81)], and stroke [0.71 (95% CI: 0.39-1.31)], compared to CR only., Conclusions: Compared to PCI, exercise-based CR associated with significantly lower odds of 18-month all-cause mortality, rehospitalization, and cardiovascular morbidity in patients with CCS, whilst combining PCI and exercise-based CR associated with lower incident heart failure only., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Heart failure (HF) and atrial fibrillation (AF), increasingly common in the aging population, are closely related and commonly found together. This article explores the relationship between AF and HF and the thromboembolic effect of these diseases. Morbidity and mortality are increased when the 2 conditions are seen together. Stroke risks are significant with AF and all subtypes of HF. This article suggests that all patients with AF and HF should be considered for anticoagulation. Current evidence suggests that non-vitamin K antagonist oral anticoagulants are effective and safe in AF and HF in comparison with warfarin., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The risk of major adverse cardiovascular events is substantially increased following a stroke. Although exercise-based cardiac rehabilitation has been shown to improve prognosis following cardiac events, it is not part of routine care for people following a stroke. We, therefore, investigated the association between cardiac rehabilitation and major adverse cardiovascular events for people following a stroke. Following a stroke, individuals have an increased risk of new-onset cardiovascular complications. However, the incidence and long-term clinical consequence of newly diagnosed cardiovascular complications following a stroke is unclear. The aim of the present study was to investigate the incidence and long-term clinical outcomes of newly diagnosed cardiovascular complications following incident ischemic stroke., Methods: A retrospective cohort study was conducted using anonymized electronic medical records from 53 participating health care organizations. Patients with incident ischemic stroke aged ≥18 years with 5 years of follow-up were included. Patients who were diagnosed with new-onset cardiovascular complications (heart failure, severe ventricular arrhythmia, atrial fibrillation, ischemic heart disease, Takotsubo syndrome) within 4-weeks (exposure) of incident ischemic stroke were 1:1 propensity score-matched (age, sex, ethnicity, comorbidities, cardiovascular care) with ischemic stroke patients who were not diagnosed with a new-onset cardiovascular complication (control). Logistic regression models produced odds ratios (OR) with 95% CIs for 5-year incidence of all-cause mortality, recurrent stroke, hospitalization, and acute myocardial infarction., Results: Of 365 383 patients with stroke with 5-year follow-up: 11.1% developed acute coronary syndrome; 8.8% atrial fibrillation/flutter; 6.4% heart failure; 1.2% severe ventricular arrythmias; and 0.1% Takotsubo syndrome within 4 weeks of incident ischemic stroke. Following propensity score matching, odds of 5-year all-cause mortality were significantly higher in stroke patients with acute coronary syndrome (odds ratio, 1.49 [95% CI, 1.44-1.54]), atrial fibrillation/flutter (1.45 [1.40-1.50]), heart failure (1.83 [1.76-1.91]), and severe ventricular arrhythmias (2.08 [1.90-2.29]), compared with matched controls. Odds of 5-year rehospitalization and acute myocardial infarction were also significantly higher for patients with stroke diagnosed with new-onset cardiovascular complications. Takotsubo syndrome was associated with significantly higher odds of 5-year composite major adverse cardiovascular events (1.89 [1.29-2.77]). Atrial fibrillation/flutter was the only new-onset cardiac complication associated with significantly higher odds of recurrent ischemic stroke at 5 years (1.10 [1.07-1.14])., Conclusions: New-onset cardiovascular complications diagnosed following an ischemic stroke are very common and associate with significantly worse 5-year prognosis in terms of major adverse cardiovascular events. People with stroke and newly diagnosed cardiovascular complications had >50% prevalence of recurrent stroke at 5 years.