Risk Of Incident Heart Failure Research Articles

Serum metabolomics improves risk stratification for incident heart failure.

Prediction and early detection of heart failure (HF) is crucial to mitigate its impact on quality of life, survival, and healthcare expenditure. Here, we explored the predictive value of serum metabolomics (168 metabolites detected by proton nuclear magnetic resonance [1H-NMR] spectroscopy) for incident HF. Leveraging data of 68 311 individuals and >0.8 million person-years of follow-up from the UK Biobank cohort, we (i) fitted per-metabolite Cox proportional hazards models to assess individual metabolite associations, and (ii) trained and validated elastic net models to predict incident HF using the serum metabolome. We benchmarked discriminative performance against a comprehensive, well-validated clinical risk score (Pooled Cohort Equations to Prevent HF [PCP-HF]). During a median follow-up of ≈12.3 years, several metabolites showed independent association with incident HF (90/168 adjusting for age and sex, 48/168 adjusting for PCP-HF). Performance-optimized risk models effectively retained key predictors representing highly correlated clusters (≈80% feature reduction). Adding metabolomics to PCP-HF improved predictive performance (Harrel's C: 0.768 vs. 0.755, ΔC = 0.013, [95% confidence interval [CI] 0.004-0.022], continuous net reclassification improvement [NRI]: 0.287 [95% CI 0.200-0.367], relative integrated discrimination improvement [IDI]: 17.47% [95% CI 9.463-27.825]). Models including age, sex and metabolomics performed almost as well as PCP-HF (Harrel's C: 0.745 vs. 0.755, ΔC = 0.010 [95% CI -0.004 to 0.027], continuous NRI: 0.097 [95% CI -0.025 to 0.217], relative IDI: 13.445% [95% CI -10.608 to 41.454]). Risk and survival stratification was improved by integrating metabolomics. Serum metabolomics improves incident HF risk prediction over PCP-HF. Scores based on age, sex and metabolomics exhibit similar predictive power to clinically-based models, potentially offering a cost-effective, standardizable, and scalable single-domain alternative.

Association between Statin Use and Chemotherapy-Induced Cardiotoxicity: A Meta-Analysis.

Background: Chemotherapy-induced cardiac dysfunction (CIC) is a significant and concerning complication observed among cancer patients. Despite the demonstrated cardioprotective benefits of statins in various cardiovascular diseases, their effectiveness in mitigating CIC remains uncertain. Objective: This meta-analysis aims to comprehensively evaluate the potential cardioprotective role of statins in patients with CIC. Methods: A systematic literature search was conducted using PubMed, Embase, and Scopus databases to identify relevant articles published from inception until 10th May 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CIs). Results: This meta-analysis comprised nine studies involving a total of 5532 patients, with 1904 in the statin group and 3628 in the non-statin group. The pooled analysis of primary outcome shows that patients who did not receive statin suffer a greater decline in the LVEF after chemotherapy compared to those who receive statin (MD, 3.55 (95% CI: 1.04-6.05), p = 0.01). Likewise, we observed a significantly higher final mean LVEF among chemotherapy patients with statin compared to the non-statin group of patients (MD, 2.08 (95% CI: 0.86-3.30), p > 0.001). Additionally, there was a lower risk of incident heart failure in the statin group compared to the non-statin group of patients (OR, 0.41 (95% CI: 0.27-0.62), p < 0.001). Lastly, the change in the mean difference for LVEDV was not statistically significant between the statin and non-statin groups (MD, 1.55 (95% CI: -5.22-8.33), p = 0.65). Conclusion: Among patients of CIC, statin use has shown cardioprotective benefits by improving left ventricular function and reducing the risk of heart failure.

Association of left atrial enlargement with heart failure events in non-valvular atrial fibrillation patients with preserved left ventricular ejection fraction.

Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little is known regarding the risk stratification for incident HF in AF patients, especially with preserved left ventricular ejection fraction (LVEF). The Fushimi AF Registry is a community-based prospective survey of AF patients. From the registry, 3002 non-valvular AF patients with preserved LVEF and with the data of antero-posterior left atrial diameter (LAD) at enrolment were investigated. Patients were stratified by LAD (<40, 40-44, 45-49, and ≥50 mm) with backgrounds and HF hospitalization incidences compared between groups. Of 3002 patients [mean age, 73.5 ± 10.7 years; women, 1226 (41%); paroxysmal AF, 1579 (53%); and mean CHA2DS2-VASc score, 3.3 ± 1.7], the mean LAD was 43 ± 8 mm. Patients with larger LAD were older and less often paroxysmal AF, with a higher CHA2DS2-VASc score (all P < 0.001). Heart failure hospitalization occurred in 412 patients during the median follow-up period of 6.0 years. Larger LAD was independently associated with a higher HF hospitalization risk [LAD ≥ 50 mm: hazard ratio (HR), 2.36; 95% confidence interval (CI), 1.75-3.18; LAD 45-49 mm: HR, 1.84; 95% CI, 1.37-2.46; and LAD 40-44 mm: HR, 1.34; 95% CI, 1.01-1.78, compared with LAD < 40 mm) after adjustment by age, sex, AF type, and CHA2DS2-VASc score. These results were also consistent across major subgroups, showing no significant interaction. Left atrial diameter is significantly associated with the risk of incident HF in AF patients with preserved LVEF, suggesting the utility of LAD regarding HF risk stratification for these patients.

Ready-to-Eat Food Environments and Risk of Incident Heart Failure: A Prospective Cohort Study.

Food environments have been linked to cardiovascular diseases; however, few studies have assessed the relationship between food environments and the risk of heart failure (HF). We aimed to evaluate the association between ready-to-eat food environments and incident HF at an individual level in a large prospective cohort. Exposure to ready-to-eat food environments, comprising pubs or bars, restaurants or cafeterias, and fast-food outlets, were individually measured as both proximity and density metrics. We also developed a composite ready-to-eat food environment density score by summing the densities of 3 types of food environments. Cox proportional analyses were applied to assess the associations of each single type and the composite food environments with HF risk. Closer proximity to and greater density of ready-to-eat food environments, particularly for pubs and bars and fast-food outlets (P<0.05 for both proximity and density metric) were associated with an elevated risk of incident HF. Compared with those with no exposure to composite ready-to-eat food environments, participants in the highest density score category had a 16% (8%-25%; P<0.0001) higher risk of HF. In addition, we found significant interactions of food environments with education, urbanicity, and density of physical activity facilities on HF risk (all Pinteraction<0.05); the ready-to-eat food environments-associated risk of HF was stronger among participants who were poorly educated, living in urban areas, and without physical activity facilities. Exposure to ready-to-eat food environments is associated with a higher risk of incident HF, suggesting the potential importance of minimizing unfavorable food environments in the prevention of HF.

Iron Deficiency and Incident Heart Failure in Older Community-Dwelling Individuals.

Among persons with prevalent heart failure (HF), iron deficiency has been linked to HF admissions, and intravenous iron replacement improves HF outcomes. Recent studies in persons with chronic kidney disease (CKD) demonstrate that iron deficiency is associated with incident HF. This study aimed to determine the relationship of iron status with incident HF in community-dwelling older adults irrespective of their kidney function. In this case-cohort study, 1,006 Cardiovascular Health Study participants (785 from the random sub-cohort [including 193 HF cases] and 221 additional HF cases [N=414 total HF cases]) aged ≥ 65years without HF (41% with CKD), we used weighted Cox models to evaluate associations of iron status with incident HF. Participants were categorized based on quartiles of transferrin saturation and ferritin as "iron replete" (27.3%), "functional iron deficiency" (7.7%), "iron deficiency" (11.8%), "mixed iron deficiency" (5.6%), "high iron" (9.3%) and "non-classified" (38.1%), consistent with prior studies. Compared to older persons who were iron replete, those with iron deficiency were at higher risk of incident HF (HR 1.47; 1.02-2.11) in models adjusting for demographics, HF risk factors, and estimated glomerular filtration rate. Other iron categories did not associate with incident HF. The relationship of iron deficiency with incident HF did not differ by CKD status (interaction P value 0.2). Among community-dwelling elders, iron deficiency is independently associated with incident HF, an association that was similar irrespective of CKD status. Our findings support conduct of clinical trials of iron replacement for prevention of HF in older adults with iron deficiency.

Self-Reported Outdoor Light Exposure Time and Incident Heart Failure.

A healthy lifestyle is an important factor for preventing heart failure. However, the association between outdoor light exposure time and heart failure is still unknown. The aim of this study was to examine the association between outdoor light exposure time and the incidence of heart failure. This cohort study included participants from the UK Biobank recruited from 2006 to 2010 who were 40 to 70 years of age and free of heart failure at baseline. The mean follow-up time was 12.61 years. The outdoor light exposure time was self-reported at baseline. A restricted cubic spline was performed to examine the potential nonlinear relationship between outdoor light exposure and the incidence of heart failure. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% CIs. During a mean follow-up of 12.61 years, 13 789 participants were first diagnosed with heart failure. There was a nonlinear (J-shaped) trend between outdoor light time and heart failure risk. Cox proportional hazard regression models showed that, compared with participants who received an average of 1.0 to 2.5 hours of outdoor light per day, those with <1.0 hours or >2.5 hours had a higher risk of heart failure after the model was adjusted for age and sex (<1.0 hours: HR, 1.27 [95% CI, 1.18-1.36]; >2.5 hours: HR, 1.11 [95% CI, 1.07-1.15]). These associations were still significant in the fully adjusted models (<1.0 hours: HR, 1.10 [95% CI, 1.03-1.18]; >2.5 hours: HR, 1.07 [95% CI, 1.03-1.11]). We found a J-shaped association between outdoor light exposure time and the risk of incident heart failure, suggesting that moderate exposure to outdoor light may be a prevention strategy for heart failure.

Association between secondhand smoke exposure and incident heart failure: The Multi-Ethnic Study of Atherosclerosis (MESA).

There are no studies on the association between secondhand smoke (SHS) exposure and incident heart failure (HF). This cohort study aimed to examine the associations of self-reported and urinary cotinine-assessed SHS exposure with incident HF. This study included 5548 non-active smoking participants aged 45-84 years and free of known cardiovascular diseases and HF at baseline who self-reported SHS exposure time in the Multi-Ethnic Study of Atherosclerosis (MESA) at baseline (2000-2002). A cohort subset of 3376 non-active smoking participants underwent urinary cotinine measurements. HF events were verified by medical records or death certificates and ascertained from baseline through 2019. Multivariable Cox proportional hazards regression analysis was used with adjustment for demographic variables, traditional cardiovascular risk factors, physical activity, tobacco pack-years and medications. During a median follow-up of 17.7 years, 353 and 196 HF events were identified in the self-report cohort and cohort subset, respectively. In the self-report cohort, compared with the SHS unexposed group (0 h/week), the highest tertile of the SHS exposed group (7-168 h/week) was not associated with incident HF (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.49-1.00; p = 0.052). In contrast, in the cohort subset, participants with detectable urinary cotinine >7.07 ng/ml had a higher risk of incident HF than those with undetectable urinary cotinine ≤7.07 ng/ml (HR 1.45, 95% CI 1.03-2.06; p = 0.034). There were no significant heterogeneities in HF risk by age, sex, race/ethnicity, or past smoking status. Secondhand smoke exposure reflected by modestly increased urinary cotinine (>7.07 ng/ml) rather than self-report in non-active smokers was associated with a 40-50% higher risk of any HF event.

Abnormal circulating steroids refine risk of progression to heart failure in ischemic heart disease.

Patients with ischemic heart disease (IHD) experience a high incidence of progression to heart failure (HF) despite current therapies. We speculated that steroid hormone metabolic disorders distinct adverse phenotypes and contribute to HF. We measured 18 steroids using liquid chromatography with tandem mass spectrometry in 2023 patients from the Registry Study of Biomarkers in Ischemic Heart Disease (BIOMS-IHD), including 1091 patients with IHD in a retrospective discovery set and 932 patients with IHD in a multicentre validation set. Our outcomes included incident HF after a median follow-up of 4 years. We demonstrated steroid-based signatures of inflammation, coronary microvascular dysfunction and left ventricular hypertrophy that were associated with subsequent HF events in patients with IHD. In both cohorts, patients with a high steroid-heart failure score (SHFS) (>1) exhibited a greater risk of incident HF than patients with a low SHFS (≤1). The SHFS further improved the prognostic accuracy beyond clinical variables (net reclassification improvement of 0.628 in the discovery set and 0.299 in the validation set) and demonstrated the maximal effect of steroid signatures in patients with IHD who had lower B-type natriuretic peptide levels (pinteraction = 0.038). A steroid-based strategy can simply and effectively identify individuals at higher HF risk who may derive benefit from more intensive follow-ups.

Plasma Ferritin Levels, Incident Heart Failure, and Cardiac Structure and Function: The ARIC Study

BackgroundWhether iron deficiency contributes to incident heart failure (HF) and cardiac dysfunction has important implications given the prevalence of iron deficiency and the availability of several therapeutics for iron repletion. ObjectivesThe aim of this study was to estimate the associations of plasma ferritin level with incident HF overall, HF phenotypes, and cardiac structure and function measures in older adults. MethodsParticipants in the ongoing, longitudinal ARIC (Atherosclerosis Risk In Communities) study who were free of prevalent HF and anemia were studied. The associations of plasma ferritin levels with incident HF overall and heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) were estimated using Cox proportional hazards regression models. Linear regression models estimated the cross-sectional associations of plasma ferritin with echocardiographic measures of cardiac structure and function. ResultsThe cohort included 3,472 individuals with a mean age of 75 ± 5 years (56% women, 14% Black individuals). In fully adjusted models, lower ferritin was associated with higher risk for incident HF overall (HR: 1.20 [95% CI: 1.08-1.34] per 50% lower ferritin level) and higher risk for incident HFpEF (HR: 1.28 [95% CI: 1.09-1.50]). Associations with incident HFrEF were not statistically significant. Lower ferritin levels were associated with higher E/e′ ratio and higher pulmonary artery systolic pressure after adjustment for demographics and HF risk factors but not with measures of left ventricular structure or systolic function. ConclusionsAmong older adults without prevalent HF or anemia, lower plasma ferritin level is associated with a higher risk for incident HF, HFpEF, and higher measures of left ventricular filling pressure.

Changes in physical activity and the risk of heart failure in newly diagnosed patients with depression: A nationwide cohort study

BackgroundDepression is known to increase the risk of heart failure (HF), and physical activity could be a potential mediator of their linkage. In this study, we examined the risk of incident HF according to changes in the level of physical activity before and after the diagnosis of depression. MethodsA South Korean National Health Insurance Sharing Service database was used. A total of 1,405,655 patients with newly diagnosed depression were included in the analyses. According to the changes in physical activity based on the recommended level of regular physical activity, participants were divided into four groups: never, beginning, maintenance, and discontinuation. The main outcome was the occurrence of HF. ResultsDuring the average follow-up period of 5.28 years (SD, 2.00 years), 69,338 participants were diagnosed with HF, with an incidence rate of 9.34 per 1000 person-years. Compared to the never group, the beginning group showed a decreased risk of HF (aHR, 0.88; 95% CI, 0.86–0.90). Compared to the maintenance group, the discontinuation group showed an increased risk of HF (aHR, 1.16; 95% CI, 1.11–1.20). ConclusionsIn the patients with depression, beginning regular physical activity was associated with a decreased risk of HF, and discontinuing regular physical activity was associated with an increased risk.

Life's Essential 8 and risk of incident heart failure in community population without cardiovascular disease: Results of the sub-cohort of China PEACE Million Persons Project

ObjectiveThe American Heart Association has introduced the Life's Essential 8 metrics to evaluate and promote cardiovascular health (CVH) and we aimed to evaluate the association of CVH and incident heart failure (HF). MethodsThe China PEACE Million Persons Project is a population-based cardiovascular disease (CVD) screening study. This was a sub-cohort of the project that included individuals free of CVD at baseline. Components and classifications of CVH, including diet, physical activity, smoking status, sleep status, body mass index (BMI), non-high density lipoprotein (non-HDL), blood glucose and blood pressure, were determined based on the Life's Essential 8. CVH status was categorized as poor, intermediate and ideal status. HF cases were identified by linking hospital records. ResultsAmong the cohort (n = 38,571, median age 54 years and women 60.5%), proportion of individuals with poor, intermediate and ideal CVH was 30.7%, 56.9% and 12.4%. After a median follow-up of 3.56 years, the incidence of HF in individuals with poor, intermediate and ideal CVH was 2.5%, 1.1% and 0.5% respectively. Compared to poor CVH, intermediate (adjusted HR: 0.52 [95% CI: 0.43–0.61]) and ideal CVH (adjusted HR: 0.38 [95% CI: 0.26–0.57]) were associated with a lower HF risk. A gradient of association between CVH and HF risk was observed (P-trend<0.001). Ideal physical activity, ideal smoking status, and intermediate and ideal status of BMI, blood glucose and blood pressure were associated with a lower HF risk. ConclusionPoor CVH was associated with an increased risk of HF, and promotion of CVH may help prevent HF development.

Plasma Total‐Tau is Related to Risk of Heart Failure in the Community

AbstractBackgroundTau is mainly expressed in the neurons of the central nervous system, with elevated cerebrospinal fluid and plasma levels noted when pathologic extracellular aggregation of tau occurs in the setting of neurodegeneration. Plasma tau and phosphorylated tau species are currently being studied as biomarkers for diagnosis, prognosis, or to measure susceptibility risk for conditions such as Alzheimer’s disease. However, the potential for circulating tau protein or other toxic entities upstream or along the tau pathway to cause cardiac dysfunction via protein misfolding or abnormal aggregation has only received limited study.MethodsWe evaluated the association of plasma total‐tau and risk of congestive heart failure in a community‐based sample from the prospective Framingham Heart Study. Adult participants free from clinical heart failure at time of blood sample (Exam 8, 2005‐2008) were included. Participants with renal failure or on dialysis were excluded. Plasma total‐tau was measured using the Simoa platform. Total‐tau plasma values were natural log‐transformed to approximate a normal distribution. Using Cox regression models, total‐tau was related to incident congestive heart failure (up to 2019), adjusting for age and sex (Model 1) and additionally adjusting for cardiovascular risk factors: systolic blood pressure, prevalent diabetes, antihypertensive medication use, smoking status, total cholesterol‐to‐high density lipoprotein ratio, and prevalent atrial fibrillation (Model 2).ResultsWe studied 2792 participants (mean age 67±9 years, 55% women) over a mean follow‐up period of 10.7±3.2 years (Table 1). There were 215 incident cases of heart failure. Each standard deviation unit increase in the log of plasma total‐tau was associated with a 42% increased risk of incident heart failure (95% confidence interval:1.26‐1.61; p&lt;0.0001) in Model 2 (Table 2). Among individuals with plasma total‐tau values in the top quintile compared to the bottom four quintiles, risk for incident heart failure was increased by 69% (1.26‐2.28; p = 0.0005).ConclusionElevated levels of plasma total‐tau at baseline in this community‐based sample were associated with incidence of congestive heart failure. Circulating tau protein, or possibly byproducts of related neurodegenerative pathways, may represent a shared substrate of protein misfolding, in the brain and the heart, resulting in Alzheimer’s disease and heart failure.

Statin Therapy Is Associated With a Lower Risk of Heart Failure in Patients With Atrial Fibrillation: A Population-Based Study.

Whether statin usecan 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. 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. Statin use was associated with a decreased risk of incident HF in a duration-dependent manner among patients with atrial fibrillation.

Infertility and Subclinical Antecedents of Heart Failure With Preserved Ejection Fraction in the Framingham Heart Study

BackgroundInfertility has been shown to be associated with a greater risk of incident heart failure with preserved ejection fraction. We studied the association of infertility with subclinical markers of heart failure with preserved ejection fraction, including echocardiographic signs of cardiac remodeling and cardiac biomarkers. Methods and ResultsA history of infertility was ascertained in 2002 women enrolled in the Framingham Heart Study. We examined the association of infertility with echocardiographic measures and cardiac biomarkers with multivariable-adjusted linear regression models. Among 2002 women (mean age 40.84 ± 9.71 years), 285 (14%) reported a history of infertility. Infertility was associated with a greater E/e′ ratio (β = 0.120, standard error 0.057, P = .04), even after adjustment for common confounders. Infertility was not associated with other echocardiographic measures or cardiac biomarkers. ConclusionsInfertility was associated with a greater E/e′ ratio, a marker of diastolic dysfunction that may signal earlier subclinical cardiac remodeling in women with infertility.

Association of cardiovascular health with incident heart failure in community population without cardiovascular disease: results of the China PEACE million persons project

Abstract Aim To evaluate the association of cardiovascular health (CVH) with incident heart failure (HF). Methods The China PEACE million persons project is a nationwide, government-funded and population-based cardiovascular disease (CVD) screening study. This was a sub-cohort study of the project that included community-dwelling adults free of CVD. Components of CVH, including diet, physical activity, smoking status, sleep status, body mass index (BMI), non-HDL, blood glucose and blood pressure, were collected using self-report questionnaires. Each component and CVH were categorized as poor, intermediate and ideal status based on the AHA Life’s Essential 8 criteria. HF cases were identified by linking hospital records. Results Among the cohort (n=38571, median age 54 years and women 60.5%), proportion of individuals with poor, intermediate and ideal CVH was 30.7%, 56.9% and 12.4% respectively. After a median follow-up of 3.6 years, the incidence of HF in individuals with poor, intermediate and ideal CVH was 2.5%, 1.1% and 0.5% (P&amp;lt;0.001). Compared to poor CVH, intermediate (adjusted HR: 0.52 [95% CI: 0.43-0.61]) and ideal CVH (adjusted HR: 0.38 [95% CI: 0.26-0.57]) were associated with a lower risk of incident HF. A gradient of association between CVH and risk of incident HF was observed (P-trend &amp;lt; 0.001). Ideal physical activity, ideal smoking status, and intermediate and ideal status of BMI, blood glucose and blood pressure were independently associated with a lower risk of incident HF. Conclusion Poor CVH was independently associated with an increased risk of incident HF and promotion of CVH may have important implications for HF prevention.Graphical abstract

Diastolic function is more sensitive than GLS in identifing cardiotoxicity. The SAFE trial results

Abstract Echocardiographic measures of diastolic dysfunction are associated with an increased risk of incident heart failure. Previous studies have shown that changes in diastolic function occur with anthracycline cancer therapy. However, they did not incorporate the newest classification of diastolic function nor evaluated the association with subsequent declines in systolic function. Design The SAFE trial is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study. Recruitment was conducted between July 2015 and June 2020. Patients with breast cancer were eligible if they had indication to primary or postoperative systemic therapy using an anthracycline-based regimen. Known cardiovascular disease or high-risk features were exclusion criteria. Cardioprotective therapy (bisoprolol(B), ramipril(R), or both drugs, as compared to placebo(P)) was administered for 1 year since chemotherapy initiation or until the end of trastuzumab therapy in the case of HER2-positive patients. Each drug was systematically titrated, up to the target dose of B(5 mg OD), R(5 mg OD), if tolerated. The primary endpoint was defined as any subclinical impairment (worsening ≥10%) of 3D left ventricular ejection fraction and global longitudinal strain (GLS) at the end-of-therapy (EOT) and at 2-year follow-up (EOF). Individual measures indicative of diastolic function (mitral E/A ratio, septal and lateral e’ velocities, indexed LA volume, TR velocity, and E/e’ ratio) were recorded and diastolic function was graded according to the 2016 ASE/EACVI guidelines. Results Out of 262 women (median age 48 years; range, 24-75 years) enrolled and treated, 222 patients completed the pre-planned cardiological assessment at 24 months. Baseline demographic, tumor, and cardiovascular profiles were similar between the study arms. All patients received anthracyclines, 217 also received taxane, and 77 adjuvant trastuzumab. Forty-nine patients were treated with neoadjuvant chemotherapy, 154 with adjuvant endocrine therapy, and 124 had postoperative radiation therapy. At EOT GLS worsened by 10% or greater in 57% of patients in the P arm, 20%, 13%, and 18% in the R, B, and R+B arms, respectively (P&amp;lt; 0.05). At EOF GLS worsened by 10% or greater in 65 % of patients in the P arm, 13%, 9%, and 10% in the R, B, and R+B arms, respectively (P&amp;lt; 0.05). In all patients, diastolic function was normal at baseline. Changes in any diastolic parameter were not significant (Table). AT EOT 9% of the patients with &amp;lt;10% GLS decrease showed diastolic dysfunction (22% in P arm, 8%, 6%, and 4% in the R, B, and R+B arms, respectively, P&amp;lt;0.05). At EOF 78% of patients with ≥10% GLS decrease showed diastolic dysfunction (Figure). Our findings provide evidence that 1. abnormal diastolic function precedes systolic dysfunction, 2 there are significant changes in diastolic function grade over time, 3. cardioprotective therapy may be useful in low-risk breast cancer patients.TableFigure

A comprehensive analysis of 30 Biomarkers and their association with cardiovascular outcomes and mortality in the UK Biobank

Abstract Background The use of a comprehensive panel of circulating biomarkers in risk estimation of cardiovascular disease and mortality in a general healthy population remains uncertain. Methods The individual association of 30 clinically available biomarkers with risk of incident heart failure (HF), atrial fibrillation (AF), stroke, myocardial infarction (MI), venous thromboembolism (VTE), and mortality was estimated within 5-years using separate logistic regression models in nearly 500,000 individuals in the UK Biobank; a prospective, population-based cohort recruited between 2006-2010. Results A total of 496,415 individuals were included (median age 58 years, 54% female). Higher concentrations of C-reactive protein, gamma-glutamyl transferase, cystatin C, and urate were associated with significantly higher odds, and albumin with lower odds, of all outcomes (Figure 1). Higher levels of sex hormone binding globulin were associated with a higher risk of AF for both sexes (men: Odds ratio [OR] per standard deviation [SD] 1.26, 95% confidence intervals [CI] 1.21-1.31; premenopausal women: OR per SD 1.20, 95% CI 1.09-1.31; postmenopausal women: OR per SD 1.41, 95% CI 1.12-1.77). No significant associations were found among pre- or postmenopausal women between estradiol and cardiovascular outcomes. For men, having estradiol ≥40 pmol/L was associated with a higher risk of mortality, HF and AF. Conclusions Several associations were found between multiple biomarkers and cardiovascular disease, and mortality, especially novel associations of hormonal markers associated with both lower and higher odds of cardiovascular disease. Further research is needed to validate these associations and explore the potential clinical applications of biomarker data.

The association between alcohol consumption and heart failure with reduced and preserved ejection fraction: the Cardiovascular Health Study

Abstract Background Alcohol consumption has been associated with a lower risk of heart failure (HF) and myocardial infarction. Nevertheless, knowledge of the relationship between alcohol consumption and the two subtypes of HF; HF with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) is lacking. Methods The Cardiovascular Health study is a US-based prospective cohort study aiming to investigate cardiovascular risk factors and outcomes (5,888 subjects, ≥65 years, follow-up 18 years). Weekly alcohol consumption was assessed by questionnaires and categorized (long-term abstainers; quit-during-follow-up; former; &amp;lt;1drinks/week, 1-&amp;lt;7drinks/week; 7-&amp;lt;14drinks/week; ≥14drinks/week. Incidence of new onset HF, HFpEF (left ventricular ejection fraction (LVEF) ≥50%) and HFrEF (LVEF &amp;lt;50%) was determined by review of available data by an expert panel. Time-dependent multivariable Cox proportional hazard models were used to investigate the associations between time-varying alcohol consumption over up to 18 years follow up and HF, HFpEF and HFrEF. Multiple imputation (5-itterations) was used on variables with &amp;gt;5% missing data (kindney-function/income). Long-term abstainers served as the reference category. Analyses were corrected for age, race, sex, body mass index, smoking status, education, marital status, physical activity, hypertension, glycemic status (normal/impaired/diabetes), kidney-function, lipid lowering medication, time-dependent myocardial infarction, stroke and atrial fibrillation. Effect modification by sex and glycemic status was investigated. Results At baseline 5,608 subjects who reported alcohol consumption were at risk for incident HF. 2,029 events occurred during follow-up (n(HFpEF) = 568, n(HFrEF) = 551, n(Unclassified) = 910). Compared with long-term abstainers, the fully-adjusted risk of HF was lower among subjects who reported consuming 1-&amp;lt;7drinks/week (hazard ratio (HR]) 0.82, 95% confidence interval (CI); 0.70-0.97), 7-13 drinks/week (HR 0.83, 95%CI; 0.69-0.99) and ≥14drinks/week (HR 0.68, 95%CI; 0.49-0.93). For HFrEF, the fully adjusted risk was lower among subjects who reported consuming ≥14drinks/week (HR: 0.40, 95% CI; 0.20-0.82) compared with long-term abstainers. For both HF and HFrEF a cardioprotective trend was observed with increasing alcohol consumption (ptrend = 0.001 and ptrend = 0.004, respectively). No significant associations were found for alcohol consumption and HFpEF (HR 0.83, 95%CI; 0.46-1.51). Effect modification was not observed. Conclusions Among older adults, increasing alcohol consumption is associated with a lower risk of incident HF and consumption of ≥14drinks/week with HFrEF, but not with HFpEF. This is likely due to the different underlying pathophysiological mechanisms leading to different entities of HF. This study provides evidence that the observed protective effects in HF are likely to be driven by HFrEF.

Prediction of incident heart failure through deep learning-based analysis of 1-lead ECGs

Abstract Background/Introduction Identification of individuals at risk for heart failure (HF) can lead to early intervention. However, large scale screening for incident HF in the general population is insufficient, partly due to the limited capacities in health care systems and number of health care specialists. One-lead ECGs, e.g. from wearables capable of deriving this biomarker, are becoming more popular in the population. This holds the potential to identify individuals at risk who could benefit from a referral to a HF specialist. Purpose We examined the ability to predict three-year HF incidence from 1-lead ECGs using a deep learning (DL) model that was trained on data from the UK Biobank (UKB). Methods The UKB was established in 2006 and contains data from 500,000 participants from the British general population. N = 100,551 1-lead ECGs from 91,898 unique participants were used for this study. This includes 57,897 3-lead resting ECGs written during ergometry exams between 2006 and 2010 (Exam 1; median age 56.7 years, 46.2% men) and at the first follow-up from 2010-2013 (Exam 2; median age 61.3 years, 49% men) and 32,828 12-lead resting ECGs which were acquired between 2014 and 2020 (Exam 3; median age 63.5 years, 48.4% men). Lead I was extracted from the ECGs for all analyses. A 1D-Convolutional Neural Network was used for prediction of the 3-year risk of incident HF. A comparison with the CHARGE-AF score was performed using a nested 6-fold cross-validation scheme. The models were evaluated using the Area Under the Curve (AUC). Results In all three exams, the DL model was able to reliably detect 3-year incident HF (AUC; Exam 1: 0.738, Exam 2: 0.822, Exam 3: 0.738) while the CHARGE-AF score provided slightly better predictions at Exam 1 and Exam 3 (AUC 0.766, 0.748), but lower results in Exam 2 (AUC 0.736). Combining both models led to increased discriminatory properties across all exams (AUC; Exam 1: 0.812, Exam 2: 0.832, Exam 3: 0.788). Conclusion The derived DL model shows high discriminatory ability in the prediction of incident HF from 1-lead ECGs. The predictive ability can be further increased when combined with simple clinical variables from the CHARGE-AF score. This study represents another step towards the application of DL-based analysis of the ECG to advance health care.

Association between cardiac time intervals and incident heart failure after acute coronary syndrome

Abstract Background Cardiac time intervals are sensitive markers of myocardial dysfunction that predisposes to heart failure (HF). Color tissue Doppler imaging (TDI) curved M-mode is a reliable method for measuring cardiac time intervals. Purpose We aimed to investigate the association between cardiac time intervals and HF in patients with acute coronary syndrome (ACS). Methods This was a retrospective cohort study of 580 ACS patients treated with percutaneous coronary intervention (PCI). Patients underwent an echocardiography examination performed a median of two days after PCI. By echocardiography cardiac time intervals including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI curved M-mode and used to derive the myocardial performance index (MPI). The outcome was incident HF. Patients with prevalent at baseline HF were excluded from the analysis. Results The final study sample consisted of 387 patients, 73% were male, the mean age was 64 years, 76% of the ACS events were STEMI and LVEF and GLS were 42% and -13.1%, respectively. During follow-up (median 4.3, IQR:1.0-6.7 years), 140 (36%) developed HF. In unadjusted analyses, longer combined indexes were associated with a higher risk of HF (IVRT/ET: HR 1.24 (1.07-1.43), P = 0.003, per 0.1 increase) and (IVCT/ET: HR 1.44 (1.10-1.91), P = 0.010, per 0.1 increase), and so was higher MPI (HR 1.20 (1.08-1.34),P = 0.001, per 0.1 increase). In addition, shorter ET was also associated with higher HF risk (HR 1.13 (1.07-1.18), P&amp;lt;0.001 per 10ms decrease). MPI and IVCT/ET showed a curvilinear association with the outcome, whereas a linear association was observed for ET and IVRT/ET to the outcome (figure 1). After multivariable adjustment for cardiovascular risk factors, only MPI (HR 1.13 (1.01-1.27), P = 0.034), ET (HR 1.09 (1.01-1.17), P = 0.025), and IVCT/ET (HR1.37 (1.04-1.81), P = 0.023) remained significantly associated with HF. Of note, left ventricular ejection fraction (LVEF) significantly modified the association between ET and HF (p for interaction = 0.002), such that ET was associated with HF even in those with preserved LVEF (&amp;gt;40%) (HR 1.13 (1.02-1.24, P = 0.017, per 10ms decrease), but not in those with reduced LVEF (HR 1.02 (0.96-1.08), P = 0.56, per 10ms decrease). These findings also persisted after adjustment for cardiovascular risk factors. Conclusion Shortened ET, prolongation of combined indexes, and higher MPI were associated with an increased risk of incident HF. In addition, shortening of the ET was associated with an increased risk of HF in patients with preserved systolic function by LVEF.