Prognostic impact of abnormal sodium burden in heart failure patients with preserved ejection fraction.

BACKGROUND: Sodium abnormality is common in patients with heart failure (HF) and is associated with adverse clinical outcomes. The aim of this study is to determine the impact of abnormal sodium burden on long-term mortality and hospitalization in HF with preserved ejection fraction (HFpEF). METHODS: We analysed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline and follow-up data (n = 1717). Abnormal sodium burden was defined as the proportion of days with abnormal sodium plasma levels (either <135 mmol/L or > 145 mmol/L). To determine the independent prognostic impact of abnormal sodium burden on the long-term clinical adverse outcomes (The primary outcome was any cause death, the secondary outcomes include cardiovascular disease death, HF hospitalization, any cause hospitalization and the primary endpoint of the original study), a multivariable Cox proportional hazard model and time-updated Cox regression model were performed. RESULTS: Abnormal sodium burden occurred in 717 patients (41.76%). A high abnormal sodium burden was associated with 1.47 (95% CI, 1.15-1.89) higher risk with any cause mortality, 1.51 (95% CI, 1.08-2.09) higher risk with CVD death and 1.31 (95% CI, 1.02-1.69) higher risk with HF hospitalization when compared with no burden group. When sodium level changes over time were accounted for in time-updated models, abnormal sodium level was still associated with poor clinical outcomes. Diuretic and spironolactone usage did not show a statistical interaction effect on the prognostic significance. CONCLUSIONS: In HFpEF patients, abnormal sodium burden was an independent predictor long-term any-cause mortality and HF hospitalization.

Early Management of Blood Lipid Levels with Non-Statin Lipid-Lowering Drugs in Acute Coronary Syndrome: A Mini Review.

Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality, despite many improvements in its prevention and management. Lipid management is an important aspect of secondary prevention after ACS. Previous studies indicate that the early use of intensive statin therapy in patients with ACS may alleviate the risk of recurrent cardiovascular events and mortality. However, many patients do not reach the target low-density lipoprotein cholesterol (LDL-C) level of < 55 mg/dL with statin monotherapy, and muscle-related adverse effects caused by statins hinder adherence to treatment. Novel non-statin agents are recommended for patients who cannot achieve the target LDL-C levels with high-intensity statin therapy and those with statin intolerance. The combination of statins and non-statins may synergistically affect intensively lowering LDL-C through different mechanisms, which could lead to better cardiovascular outcomes than statin monotherapy. However, it remains uncertain whether the early use of combination lipid-lowering therapy is more beneficial. The present review summarizes the benefits of intensive statin monotherapy and their early combination with non-statin medications including ezetimibe, PCSK9 inhibitors, inclisiran, and bempedoic acid (BDA) in the management of ACS.

The use of non-vitamin K antagonist oral anticoagulants in chronic thromboembolic pulmonary hypertension: an updated meta-analysis.

Studies have demonstrated the beneficial effects of non-vitamin K antagonist oral anticoagulants (NOACs) for the treatment of atrial fibrillation and venous thromboembolism (VTE). The impact of NOACs on chronic thromboembolic pulmonary hypertension (CTEPH) remains controversial. This meta-analysis was conducted to investigate the effectiveness and safety of NOACs compared with vitamin K antagonists (VKAs) in patients with CTEPH. A comprehensive search of PubMed, Embase, and Cochrane Library was conducted for relevant studies, encompassing data from inception until November 2023. The data were pooled using a fixed-effects model if the I2 value was less than 50%; otherwise, a random-effects model was employed. Overall, two randomized controlled trials (RCTs) and eight observational studies involving 4556 patients with CTEPH were included. Patients receiving NOACs exhibited a significantly lower incidence of all-cause mortality (odds ratio [OR] = 0.52, 95% confidence interval [CI]: 0.36-0.76) and major bleeding (OR = 0.58, 95% CI: 0.36-0.92) compared to those with VKAs. There were no significant differences in the rate of VTE recurrence (OR = 1.07, 95% CI: 0.72-1.59), total bleeding (OR = 0.78, 95% CI: 0.60-1.01), and minor bleeding (OR = 1.11, 95% CI: 0.73-1.69) between the two studied groups. Similar results were found in the subgroup analysis and sensitivity analysis.This meta-analysis provided evidence that NOACs could be superior to VKAs for the treatment of CTEPH. NOACs might be safe and a convenient alternative to VKAs for thromboprophylaxis in patients with CTEPH.

Atherogenic lipid profile in patients with statin treatment after acute coronary syndrome: a real-world analysis from Chinese cardiovascular association database.

BACKGROUND: Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients after acute coronary syndrome (ACS). Knowledge regarding the impact of statins on lipid profile remains limited. METHODS: We retrospectively analysed multicenter, real-world data from the Chinese Cardiovascular Association Database-iHeart Project. Patients with a primary diagnosis of ACS from 2014 to 2021 during index hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed target achievement of atherogenic lipid profile, including apolipoprotein B (< 80 mg/dL), low-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L), lipoprotein(a) [Lp(a)] (< 30 mg/dL), triglycerides (< 1.7 mmol/L), remnant cholesterol (RC) (< 0.78 mmol/L), non-high-density lipoprotein cholesterol (< 2.6 mmol/L) at baseline and follow-up. Multivariate Cox regression models were employed to investigate the association between patient characteristics and target achievement. RESULTS: Among 4861 patients, the mean age was 64.9 years. Only 7.8% of patients had all atherogenic lipids within the target range at follow-up. The proportion of target achievement was for LDL-C 42.7%, Lp(a) 73.3%, and RC 78.5%. Patients with female sex, younger age, myocardial infarction, hypertension, and hypercholesteremia were less likely to control LDL-C, Lp(a), and RC. An increase in the burden of comorbidities was negatively associated with LDL-C and Lp(a) achievements but not with RC. CONCLUSIONS: A substantial gap exists between lipid control and the targets recommended by contemporary guidelines. Novel therapeutics targeting the whole atherogenic lipid profile will be warranted to improve cardiovascular outcomes.

Association between epicardial adipose tissue and incident heart failure mediating by alteration of natriuretic peptide and myocardial strain.

BACKGROUND: Epicardial adipose tissue (EAT) has been suggested to exert deleterious effects on myocardium and cardiovascular disease (CVD) consequence. We evaluated the associations of EAT thickness with adverse outcomes and its potential mediators in the community. METHODS: Participants without heart failure (HF) who had undergone cardiac magnetic resonance (CMR) to measure EAT thickness over the right ventricular free wall from the Framingham Heart Study were included. The correlation of EAT thickness with 85 circulating biomarkers and cardiometric parameters was assessed in linear regression models. The occurrence of HF, atrial fibrillation, coronary heart disease (CHD), and other adverse events was tracked since CMR was implemented. Their associations with EAT thickness and the mediators were evaluated using Cox regression and causal mediation analysis. RESULTS: Of 1554 participants, 53.0% were females. Mean age, body mass index, and EAT thickness were 63.3 years, 28.1 kg/m2, and 9.8 mm, respectively. After fully adjusting, EAT thickness positively correlated with CRP, LEP, GDF15, MMP8, MMP9, ORM1, ANGPTL3, and SERPINE1 and negatively correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP), IGFBP1, IGFBP2, AGER, CNTN1, and MCAM. Increasing EAT thickness was associated with smaller left ventricular end-diastolic dimension, thicker left ventricular wall thickness, and worse global longitudinal strain (GLS). During a median follow-up of 12.7 years, 101 incident HF occurred. Per 1-standard deviation increment of EAT thickness was associated with a higher risk of HF (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.19-1.72, P < 0.001) and the composite outcome consisting of myocardial infarction, ischemic stroke, HF, and death from CVD (adjusted HR [95% CI], 1.23 [1.07-1.40], P = 0.003). Mediation effect in the association between thicker EAT and higher risk of HF was observed with NT-proBNP (HR [95% CI], 0.95 [0.92-0.98], P = 0.011) and GLS (HR [95% CI], 1.04 [1.01-1.07], P = 0.032). CONCLUSIONS: EAT thickness was correlated with inflammation and fibrosis-related circulating biomarkers, cardiac concentric change, myocardial strain impairment, incident HF risk, and overall CVD risk. NT-proBNP and GLS might partially mediate the effect of thickened EAT on the risk of HF. EAT could refine the assessment of CVD risk and become a new therapeutic target of cardiometabolic diseases. TRIAL REGISTRATION: URL: https://clinicaltrials.gov . Identifier: NCT00005121.

A simple ATTR-CM score to identify transthyretin amyloid cardiomyopathy burden in HFpEF patients.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is often found in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence regarding ATTR-CM and prognosis in HFpEF remains scarce. This study sought to determine whether the ATTR-CM burden was associated with clinical outcomes in HFpEF patients. METHODS: We evaluated the associations of baseline ATTR-CM score with adverse outcomes in HFpEF patients from the TOPCAT trial using the Cox proportional hazards model or the competing risk regression model. The discriminatory ability of the ATTR-CM score was assessed using the area under the time-dependent receiver operating characteristic curve (AUC). RESULTS: We included 870 HFpEF patients, 18.9% of which had an ATTR-CM score ≥6. Per 1 increment in the ATTR-CM score was significantly associated with an increased risk of the primary outcome (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.12-1.27) with an AUC of 0.652 (0.594-0.711), whereas patients with ATTR-CM score ≥6 presented higher risks of the primary outcome (adjusted HR 2.20, 95% CI 1.65-2.95). Similar results were observed toward the secondary outcomes. CONCLUSIONS: The simple ATTR-CM score identified an 18.9% ATTR-CM burden in HFpEF patients, and a higher ATTR-CM burden might predict adverse outcomes with moderate discriminatory abilities in HFpEF.

Identification of a long noncoding RNA Gm17501 as a novel negative regulator of cardiac hypertrophy.

Pathological cardiac hypertrophy is an independent risk factor for the development of heart failure. Long noncoding RNAs (lncRNAs), an emerging class of non-protein-coding transcripts, are involved in regulation of multiple cardiac diseases through diverse molecular mechanism, whereas the role of cytoplasmic lncRNAs in regulating cardiac hypertrophy remains unclear. In this study, we identified a novel and functional long noncoding RNA Gm17501, which was predominantly expressed in the cytoplasm of cardiomyocytes. The expression level of lncRNA Gm17501 was altered in cardiac hypertrophy induced by pressure overload and phenylephrine treatment. Moreover, lncRNA Gm17501 expression was decreased in the heart tissue of patients with heart failure. Silencing lncRNA Gm17501 aggravated cardiac hypertrophy under pathological stress. Inhibition of lncRNA Gm17501 did not alter the expression of nearby genes but decreased mRNA level of calcium handling proteins which were involved in cardiac contraction. Therefore, the cytoplasmic lncRNA Gm17501 might protect cardiomyocytes against hypertrophy, possibly by maintaining calcium signaling pathway.

Associations of long-term mortality with serum uric acid at admission in acute decompensated heart failure with different phenotypes.

BACKGROUND AND AIMS: It remains unclear whether the long-term prognostic value of serum uric acid (SUA) at admission differs in acute decompensated heart failure (HF) patients across the spectrum of left ventricular ejection fraction (EF). METHODS AND RESULTS: In 2375 patients (38.9% women; mean age, 68.8 years), we assessed the risk of long-term (>1 year) all-cause mortality associated with per 1-SD increase in SUA at admission, using multivariable Cox regression in HF with preserved (HFpEF), mildly reduced (HFmrEF) and reduced (HFrEF) EF. During a median follow-up of 4.1 years, the long-term mortality rate was 39.9%. In all patients, the multivariable-adjusted hazard ratio (HR) expressing the risk of long-term mortality associated with SUA was 1.18 (95% CI, 1.11-1.26; P < 0.001). Compared with the low tertile of the SUA distribution, the sex- and age-adjusted cumulative incidence of long-term mortality was higher in the top tertile. In patients with HFpEF and HFrEF, SUA predicted the risk of long-term mortality with HRs amounting to 1.12 (95% CI, 1.02-1.21; P = 0.012) and 1.28 (95% CI, 1.12-1.47; P < 0.001), respectively. However, there were no associations between the risk of mortality and SUA in HFmrEF. Furthermore, age, sex, NYHA class, and the prevalence of coronary heart disease interacted significantly with SUA for predicting long-term mortality. CONCLUSION: Higher levels of SUA at admission were associated with higher risk of long-term mortality in patients with different HF subtypes. The risk conferred by SUA was age and sex dependent. Our observations highlight that measuring SUA at admission may help to improve risk stratification.

Cardiac CIP protein regulates dystrophic cardiomyopathy.

Heart failure is a leading cause of fatality in Duchenne muscular dystrophy (DMD) patients. Previously, we discovered that cardiac and skeletal-muscle-enriched CIP proteins play important roles in cardiac function. Here, we report that CIP, a striated muscle-specific protein, participates in the regulation of dystrophic cardiomyopathy. Using a mouse model of human DMD, we found that deletion of CIP leads to dilated cardiomyopathy and heart failure in young, non-syndromic mdx mice. Conversely, transgenic overexpression of CIP reduces pathological dystrophic cardiomyopathy in old, syndromic mdx mice. Genome-wide transcriptome analyses reveal that molecular pathways involving fibrogenesis and oxidative stress are affected in CIP-mediated dystrophic cardiomyopathy. Mechanistically, we found that CIP interacts with dystrophin and calcineurin (CnA) to suppress the CnA-Nuclear Factor of Activated T cells (NFAT) pathway, which results in decreased expression of Nox4, a key component of the oxidative stress pathway. Overexpression of Nox4 accelerates the development of dystrophic cardiomyopathy in mdx mice. Our study indicates CIP is a modifier of dystrophic cardiomyopathy and a potential therapeutic target for this devastating disease.

Effectiveness of early rhythm control in improving clinical outcomes in patients with atrial fibrillation: a systematic review and meta-analysis.

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).

Distinct implications of body mass index in different subgroups of nonobese patients with heart failure with preserved ejection fraction: a latent class analysis of data from the TOPCAT trial.

BACKGROUND: Obesity is a well-defined risk factor for heart failure with preserved ejection fraction (HFpEF), but it is associated with a better prognosis in patients with diagnosed HFpEF. The paradoxically poor prognosis in nonobese patients with HFpEF may be driven by a subset of high-risk patients, which suggests that the nonobese HFpEF subpopulation is heterogeneous. METHODS: Latent class analysis (LCA) was adopted to identify the potential subgroups of 623 nonobese patients enrolled in the TOPCAT trial. The baseline characteristics of the identified nonobese subgroups were compared with each other and with the obese patients. The risks of all-cause, cardiovascular, and noncardiovascular mortality, and an HF composite outcome were also compared. RESULTS: Two subgroups of nonobese patients with HFpEF (the physiological non-obesity and the pathological non-obesity) were identified. The obese patients were younger than both nonobese subgroups. The clinical profile of patients with pathological non-obesity was poorer than that of patients with physiological non-obesity. They had more comorbidities, more severe HF, poorer quality of life, and lower levels of physical activity. Patients with pathological non-obesity showed low serum hemoglobin and albumin levels. After 2 years of follow-up, more patients in the pathological group lost ≥ 10% of body weight compared with those in the physiological group (11.34% vs. 4.19%, P = 0.009). The prognostic implications of the two subgroups were opposite. Compared to patients with obesity, patients with physiological non-obesity had a 47% decrease in the risk of HF composite outcome (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.40-0.70, P<0.001) and a trend of decreased all-cause mortality risk (HR 0.75, 95% CI 0.55-1.01, P=0.06), while patients with pathological non-obesity had a 59% increase (HR 1.59, 95% CI 1.24-2.02, P<0.001) in all-cause mortality risk. CONCLUSIONS: Two subgroups of nonobese patients with HFpEF with distinct clinical profiles and prognostic implications were identified. The low BMI was likely physiological in one group but pathological in the other group. Using a data-driven approach, our study provided an alternative explanation for the "obesity paradox" that the poor prognosis of nonobese patients with HFpEF was driven by a pathological subgroup.

The cardiac translational landscape reveals that micropeptides are new players involved in cardiomyocyte hypertrophy.

Hypertrophic growth of cardiomyocytes is one of the major compensatory responses in the heart after physiological or pathological stimulation. Protein synthesis enhancement, which is mediated by the translation of messenger RNAs, is one of the main features of cardiomyocyte hypertrophy. Although the transcriptome shift caused by cardiac hypertrophy induced by different stimuli has been extensively investigated, translatome dynamics in this cellular process has been less studied. Here, we generated a nucleotide-resolution translatome as well as transcriptome data from isolated primary cardiomyocytes undergoing hypertrophy. More than 10,000 open reading frames (ORFs) were detected from the deep sequencing of ribosome-protected fragments (Ribo-seq), which orchestrated the shift of the translatome in hypertrophied cardiomyocytes. Our data suggest that rather than increase the translational rate of ribosomes, the increased efficiency of protein synthesis in cardiomyocyte hypertrophy was attributable to an increased quantity of ribosomes. In addition, more than 100 uncharacterized short ORFs (sORFs) were detected in long noncoding RNA genes from Ribo-seq with potential of micropeptide coding. In a random test of 15 candidates, the coding potential of 11 sORFs was experimentally supported. Three micropeptides were identified to regulate cardiomyocyte hypertrophy by modulating the activities of oxidative phosphorylation, the calcium signaling pathway, and the mitogen-activated protein kinase (MAPK) pathway. Our study provides a genome-wide overview of the translational controls behind cardiomyocyte hypertrophy and demonstrates an unrecognized role of micropeptides in cardiomyocyte biology.

Comparative Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients.

BACKGROUND AND PURPOSE: Several observational studies have compared the effect of the non-vitamin K antagonist oral anticoagulants to each other in patients with atrial fibrillation. However, confounding by indication is a major problem when comparing non-vitamin K antagonist oral anticoagulant treatments in some of these studies. This meta-analysis was conducted to compare the effectiveness and safety between non-vitamin K antagonist oral anticoagulant and non-vitamin K antagonist oral anticoagulant by only including the propensity score matching studies. METHODS: We systematically searched the PubMed and Ovid databases until May 2020 to identify relevant observational studies. Hazard ratios (HRs) and 95% CIs of the reported outcomes were collected and then pooled by a random-effects model complemented with an inverse variance heterogeneity or quality effects model. RESULTS: A total of 17 retrospective cohort studies were included in this meta-analysis. Compared with dabigatran use, the use of rivaroxaban was significantly associated with increased risks of stroke or systemic embolism (HR, 1.16 [95% CI, 1.05-1.29]) and major bleeding (HR, 1.32 [95% CI, 1.24-1.41]), whereas the use of apixaban was associated with a reduced risk of major bleeding (HR, 0.78 [95% CI, 0.67-0.90]) but not stroke or systemic embolism (HR, 0.84 [95% CI, 0.56-1.28]). Compared with rivaroxaban use, the use of apixaban was associated with a decreased risk of major bleeding (HR, 0.63 [95% CI, 0.54-0.73]) but not stroke or systemic embolism (HR, 0.83 [95% CI, 0.67-1.04]). Reanalyses with the inverse variance heterogeneity or quality effects model produced similar results as the random-effects model. CONCLUSIONS: Current observational comparisons with propensity score matching methods suggest that apixaban might be a better choice compared with dabigatran or rivaroxaban for stroke prevention in atrial fibrillation patients.

C2HEST score predicts clinical outcomes in heart failure with preserved ejection fraction: a secondary analysis of the TOPCAT trial.

BACKGROUND: The C2HEST score has been validated for predicting AF in the general population or post-stroke patients. We aimed to assess whether this risk score could predict incident AF and other clinical outcomes in heart failure with preserved ejection fraction (HFpEF) patients. METHODS: A total of 2202 HFpEF patients without baseline AF in the TOPCAT trial were stratified by baseline C2HEST score. Cox proportional hazard model and competing risk regression model was used to explore the relationship between C2HEST score and outcomes, including incident AF, stroke, all-cause death, cardiovascular death, any hospitalization, and HF hospitalization. The discriminative ability of the C2HEST score for various outcomes was assessed by calculating the area under the curve (AUC). RESULTS: The incidence rates of incident AF, stroke, all-cause death, cardiovascular death, any hospitalization, and HF hospitalization were 1.79, 0.70, 3.81, 2.42, 15.50, and 3.32 per 100 person-years, respectively. When the C2HEST score was analyzed as a continuous variable, increased C2HEST score was associated with increased risk of incident AF (HR 1.50, 95% CI 1.29-1.75), as well as increased risks of all-cause death, cardiovascular death, any hospitalization, and HF hospitalization. The AUC for the C2HEST score in predicting incident AF (0.694, 95% CI 0.640-0.748) was higher than all-cause death, cardiovascular death, any hospitalization, or HF hospitalization. CONCLUSIONS: The C2HEST score could predict the risk of incident AF as well as death and hospitalization with moderately good predictive abilities in patients with HFpEF. Its simplicity may allow the possibility of quick risk assessments in busy clinical settings.

Living Alone and Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: In patients with heart failure with preserved ejection fraction (HFpEF), whether living alone could contribute to a poor prognosis remains unknown. We sought to investigate the association of living alone with clinical outcomes in patients with HFpEF. METHODS: Symptomatic patients with HFpEF with a follow-up of 3.3 years (data collected from August 2006 to June 2013) in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial were classified as patients living alone and those living with others. The primary outcome was defined as a composite of cardiovascular death, aborted cardiac arrest, or HF hospitalization. RESULTS: A total of 3103 patients with HFpEF were included; 25.2% of them were living alone and were older, predominantly female, and less likely to be White and have more comorbidities compared with the other patients. After multivariate adjustment for confounders, living alone was associated with increased risks of HF hospitalization (hazard ratio [HR] = 1.29, 95% confidence interval [CI] = 1.03-1.61) and any hospitalization (HR = 1.26, 95% CI = 1.12-1.42). A significantly increased risk of any hospitalization (HR = 1.16, 95% CI = 1.01-1.34) was also observed in the Americas-based sample. In addition, each year increase in age, female sex, non-White race, New York Heart Association functional classes III and IV, dyslipidemia, and chronic obstructive pulmonary disease were independently associated with living alone. CONCLUSIONS: We assessed the effect of living arrangement status on clinical outcomes in patients with HFpEF and suggested that living alone was associated with an independent increase in any hospitalization.Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00094302.

Major depression and clinical outcomes in patients with heart failure with preserved ejection fraction.

OBJECTIVE: Limited data have been published concerning about depression in heart failure with preserved ejection fraction (HFpEF). Besides, among HFpEF patients with depression, the efficacy of antidepressants is poorly defined. Therefore, our current study was aimed to examine the relationship between major depression and clinical outcomes in HFpEF patients and further address the effects of antidepressants on prognosis in patients with major depression and HFpEF. METHODS: A total of 1431 patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) were divided into 2 groups according to the baseline depression status. Major depression was diagnosed if the Patient Health Questionnaire-9 score (PHQ-9) ≥ 10. Univariable and multivariable Cox proportional hazards models tested the association of major depression with outcomes and the effects of antidepressants among HFpEF patients with major depression during a follow-up of 6 years. RESULTS: 26.7% (382/1431) of patients were diagnosed with major depression. After multivariable adjustment, major depression at baseline was not significantly associated with cardiovascular outcomes (fully adjusted hazard ratio (aHR) 0.95 [0.76-1.18] for primary outcomes; aHR: 0.86 [0.67-1.10] for HF hospitalization; aHR: 1.06 [0.91-1.23] for any hospitalization; aHR: 1.00 [0.70-1.43] for cardiovascular death; aHR: 1.24 [0.96-1.61] for all-cause death). Additionally, among HFpEF patients with major depression, the use of antidepressants was not associated with adverse events (P > .05 for all analyses). CONCLUSIONS: In HFpEF patients, major depression at baseline did not increase mortality or rehospitalization. Additionally, treatment with antidepressants might not improve prognosis among HFpEF patients with major depression. Future studies are warranted to explore the effects of antidepressants on HFpEF patients with depression.

Effect of Rivaroxaban or Apixaban in Atrial Fibrillation Patients with Stage 4-5 Chronic Kidney Disease or on Dialysis.

BACKGROUND: Anticoagulant treatment in non-valvular atrial fibrillation (AF) patients with severe chronic kidney disease (CKD) or on dialysis remains a matter of debate. The object of this study was to quantify the benefit-risk profiles of rivaroxaban or apixaban versus warfarin in AF patients with stage 4-5 CKD or on dialysis. METHOD: A comprehensive search of the Cochrane Library, PubMed, Ovid, and Google Scholar databases was performed for eligible studies that comparing the effect and safety of rivaroxaban or apixaban versus warfarin in AF patients with stage 4-5 CKD or on dialysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were abstracted, and then pooled using a random-effects model. RESULTS: A total of seven studies, one post hoc analysis of RCT and six observational cohorts, were included in this meta-analysis. Compared with warfarin use, the use of rivaroxaban or apixaban was significantly associated with reduced risks of all-cause death (HR = 0.82, 95% CI 0.72-0.93) and gastrointestinal bleeding (HR = 0.87, 95% CI 0.80-0.95). There were no significant differences in the risks of stroke or systemic embolism (rivaroxaban, HR = 0.71, 95% CI 0.43-1.19; apixaban, HR = 0.86, 95%CI 0.68-1.09) and major bleeding (rivaroxaban, HR = 0.96, 95% CI 0.64-1.45; apixaban, HR = 0.56, 95%CI 0.28-1.12). CONCLUSIONS: Current evidence suggests that rivaroxaban or apixaban are safe and at least as effective as warfarin in patients with AF and stage 4-5 CKD or on dialysis.

Effectiveness of Levoamlodipine Maleate for Hypertension Compared with Amlodipine Besylate: a Pragmatic Comparative Effectiveness Study.

PURPOSE: Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting. METHODS: This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness. RESULTS: Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient. CONCLUSION: In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01844570 registered at May 1, 2013.

Meta-analysis of metabolic syndrome and its individual components with risk of atrial fibrillation in different populations.

BACKGROUND: Recent studies have reported the effects of metabolic syndrome (MetS) and its components on atrial fibrillation (AF), but the results remain controversial. Therefore, we performed a meta-analysis to evaluate the relationship between MetS and AF risk. METHODS: Studies were searched from the Cochrane library, PubMed, and Embase databases through May 2020. Adjusted hazard ratios (HRs) and its corresponding 95% confidence intervals (CIs) were extracted and then pooled by using a random effects model. RESULTS: A total of 6 observational cohort studies were finally included. In the pooled analysis, MetS was associated with an increased risk of AF (HR 1.57; 95% CI 1.40-1.77; P < 0.01). And the components of MetS including abdominal obesity (HR 1.37; 95% CI 1.36-1.38; P < 0.01), elevated blood pressure (HR 1.56; 95% CI 1.46-1.66; P < 0.01), elevated fasting glucose (HR 1.18; 95% CI 1.15-1.21; P < 0.01) and low high density cholesterol (HDL) (HR 1.18; 95% CI 1.06-1.32; P < 0.01) was also associated with an increased risk of AF, while high triglyceride (HR 0.99; 95% CI 0.87-1.11, P = 0.82) was not. CONCLUSIONS: Our present meta-analysis suggested that MetS, as well as its components including abdominal obesity, elevated blood pressure, elevated fasting glucose and low HDL cholesterol were associated with an increase in the risk of AF.

An electrographic AV optimization for the maximum integrative atrioventricular and ventricular resynchronization in CRT.

BACKGROUND: Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to obtain the maximum integrative effects of AV and ventricular resynchronization (opt-AV). METHODS: Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was < 20 ms, and to be the AV delay with the maximal aortic velocity-time integral between AVopt-AV and AVopt-V when their difference was > 20 ms. RESULTS: The results showed that sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/Pend-Ap) (P < 0.05). Sensing/pacing AVopt-V (SAVopt-V/PAVopt-V) was correlated with the intrinsic AV conduction time (As-Vs/Ap-Vs) (P < 0.01). The percentages of patients with more than 20 ms differences between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were 62.9% and 57.1%, respectively. Among them, opt-AV was linearly correlated with SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The sensing opt-AV (opt-SAV) = 0.1 × SAVopt-AV + 0.4 × SAVopt-V + 70 ms (R2 = 0.665, P < 0.01) and the pacing opt-AV (opt-PAV) = 0.25 × PAVopt-AV + 0.5 × PAVopt-V + 30 ms (R2 = 0.560, P < 0.01). CONCLUSION: The SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were correlated with the atrial activation time and the intrinsic AV conduction interval respectively. Almost half of the patients had a > 20 ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.