Symptom Burden of Atrial Fibrillation and Its Relation to Interventions and Outcome in Europe.

BACKGROUND: Little is known about the association of atrial fibrillation symptom burden with quality of life and outcomes. METHODS AND RESULTS: In the Prevention of Thromboembolic Events-European Registry in Atrial Fibrillation (n=6196 patients with atrial fibrillation; mean±SD age, 71.8±10.4 years; 39.7% women), we assessed European Heart Rhythm Association score symptoms and calculated correlations with the standardized health status questionnaire (EQ-5D-5L). Patients were followed up for atrial fibrillation therapies and outcomes (stroke/transient ischemic attack/arterial thromboembolism, coronary events, heart failure, and major bleeding) over 1 year. Most individuals (92%) experienced symptoms. Correlations with health status and quality of life were modest. In multivariable-adjusted regression models, the dichotomized European Heart Rhythm Association score (intermediate/frequent versus never/occasional symptoms) was associated with cardioversions (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.01-1.45) and catheter ablation (OR, 1.97; 95% CI, 1.44-2.69), and inversely related with heart rate control (OR, 0.80; 95% CI, 0.70-0.92) and heart failure incidence (OR, 1.65; 95% CI, 1.16-2.34). Anxiety was inversely related with stroke/transient ischemic attack/arterial thromboembolism (OR, 0.55; 95% CI, 0.32-0.93), whereas chest pain related positively with coronary events (OR, 2.45; 95% CI, 1.42-4.22). Fatigue (OR, 1.84; 95% CI, 1.30-2.60), dyspnea (OR, 2.33; 95% CI, 1.63-3.33), and anxiety (OR, 1.72; 95% CI, 1.16-2.55) were associated with heart failure incidence. Palpitations were positively associated with cardioversion (OR, 1.32; 95% CI, 1.08-1.61) and ablation therapy (OR, 2.02; 95% CI, 1.48-2.76). CONCLUSIONS: A higher symptom burden, in particular palpitations, predicted interventions to restore sinus rhythm. The score itself had limited predictive value, but its individual components were related to different and specific clinical events, and may thus be helpful to target patient management.

Atrial Fibrillation Manifestations Risk Factors and Sex Differences in a Population-Based Cohort (From the Gutenberg Health Study).

Sex differences in cardiovascular risk factors, cardiac structure and function, and disease and symptom burden in the common arrhythmia atrial fibrillation (AF) have not been investigated systematically at the population level. Cross-sectional data of 14,796 subjects (age range 35 to 74 years, 50.5% men) from the population-based Gutenberg Health Study were examined to show the distribution of cardiovascular risk factors by AF status and sex, and to determine sex-specific predictors for AF. The prevalence of AF was higher in men (4.3%) than in women (1.9%). Men had a worse cardiovascular risk factor profile, a higher prevalence of cardiovascular disease, but fewer symptoms than women. Age-adjusted Cox regressions showed sex interactions in the association of high-density lipoprotein-cholesterol, triglycerides, diabetes mellitus, coronary artery disease, myocardial infarction, generalized anxiety disorder, and heart rate with AF. After multivariable adjustment, sex interactions were seen for thickness of interventricular end-diastolic septum, odds ratio (OR) per standard deviation (SD), 95% confidence interval women: 0.9 (0.8, 1.1), men: 1.2 (1.1, 1.4), interaction p value = 0.02; left atrial diameter index, OR per SD women: 1.5 (1.3, 1.8), men: 1.9 (1.7, 2.1), interaction p value = 0.03; and myocardial infarction, OR women: 2.7 (1.3, 5.6), men: 0.7 (0.5, 1.1), interaction p value = 0.002. In conclusion, in our large cohort, we observed substantial sex differences in AF distribution and clinical characteristics including comorbidities, symptom burden, and structural cardiac changes.

Gender differences in clinical presentation and 1-year outcomes in atrial fibrillation.

OBJECTIVES: Our objective was to examine gender differences in clinical presentation, management and prognosis of atrial fibrillation (AF) in a contemporary cohort. METHODS: In 6412 patients, 39.7% women, of the PREvention oF thromboembolic events - European Registry in Atrial Fibrillation, we examined gender differences in symptoms, risk factors, therapies and 1-year incidence of adverse outcomes. RESULTS: Men with AF were on average younger than women (mean±SD: 70.1±10.7 vs 74.1±9.7 years, p<0.0001). Women more frequently had at least one AF-related symptom at least occasionally compared with men (95.4% in women, 89.8% in men, p<0.0001). Prescription of oral anticoagulation was similar, with an increase of non-vitamin K antagonist oral anticoagulants from 5.9% to 12.6% in women and from 6.2% to 12.6% in men, p<0.0001 for both.Men were more frequently treated with electrical cardioversion and ablation (20.6% and 6.3%, respectively) than women (14.9% and 3.3%, respectively), p<0.0001. Women had 65% (OR: 0.35; 95% CI (0.22 to 0.56)) lower age-adjusted and country-adjusted odds of coronary revascularisation, 40% (OR: 0.60; (0.38 to 0.93)) lower odds of acute coronary syndrome and 20% (OR: 0.80; (0.68 to 0.96)) lower odds of heart failure at 1 year. There were no statistically significant gender differences in 1-year stroke/transient ischaemic attack/arterial thromboembolism and major bleeding events. CONCLUSION: In a 'real-world' European AF registry, women were more symptomatic but less likely to receive invasive rhythm control therapy such as electrical cardioversion or ablation. Further study is needed to confirm that these differences do not disadvantage women with AF.

FEV1 and FVC predict all-cause mortality independent of cardiac function - Results from the population-based Gutenberg Health Study.

BACKGROUND: Lung function has previously been related to increased mortality. Whether pulmonary impairment is associated with an increased mortality independent of cardiac dysfunction remains unclear. METHODS: In 15010 individuals from the general population (age range 35-74years, 51% men) in the Gutenberg Health Study we performed spirometry and transthoracic echocardiography. N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and high-sensitive troponin I (hsTnI) were measured in all individuals. 1819 individuals with pulmonary diseases were excluded from further analysis. RESULTS: The median for forced expiratory volume in 1s (FEV1) was 94.2% and for forced vital capacity (FVC) 94.2% as a percentage of their predicted values. The median FEV1/FVC ratio was 79.1%. In 13191 subjects, 335 deaths were verified from death certificate over a median follow-up of 5.5years. Multivariable-adjusted Cox regression analyses for common cardiovascular risk factors and heart failure revealed that an increase of one standard deviation (SD) of percent predicted (%pred.) FEV1 was associated with a 22% risk reduction (hazard ratio [HR] per SD 0.78 [95% confidence interval (CI): 0.70, 0.86]). The association remained statistically significant after additional adjustment for diastolic dysfunction, Nt-proBNP or hsTnI. Comparable results were seen for %pred. FVC. After adjustment, no association of FEV1/FVC ratio with mortality could be shown. No significant interaction by heart failure was observed. CONCLUSIONS: The lung function parameters FEV1 and FVC, but not FEV1/FVC ratio, were related to all-cause mortality in individuals from the general population independent of cardiac function.

Subclinical impairment of lung function is related to mild cardiac dysfunction and manifest heart failure in the general population.

BACKGROUND: Lung function impairment has previously been related to heart failure, although no overt cardiovascular or structural heart disease is present. The extent to which pulmonary function is related to subclinical left ventricular impairment in the general population remains to be investigated. METHODS: 15010 individuals from the general population (mean age 55±11years, 50.5% men) in the Gutenberg Health Study underwent spirometry, transthoracic echocardiography and biomarker measurement. Forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) in percent of the predicted value and FEV1/FVC ratio were associated with echocardiographic measures of cardiac structure, systolic and diastolic function, biomarkers of cardiac necrosis (high-sensitive troponin I, hsTnI) and stress (N-terminal pro-B-type natriuretic peptide, Nt-proBNP) and heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF). RESULTS: Percent predicted FEV1 and FVC were significantly associated with hsTnI (P<0.001) and Nt-proBNP (P<0.001). Additionally, FEV1/FVC ratio was significantly related to hsTnI (P=0.0043) and Nt-proBNP (P<0.001). In the multivariable-adjusted linear regression analyses strongest associations were observed for percent predicted FEV1 and FVC with LVESD, E/e', SV and EF. FEV1/FVC ratio was significantly related with SV and EF. The three lung function parameters were significantly (P<0.001) associated with HFpEF and HFrEF. Associations remained statistically significant after exclusion of individuals with COPD. CONCLUSIONS: FEV1, FVC and FEV1/FVC ratio were associated with systolic and diastolic function and manifest heart failure. Our observations could show, that subclinical lung function impairment is related to a measurable reduction of left ventricular filling and cardiac output in the general population.

Sex Differences in Correlates of Intermediate Phenotypes and Prevalent Cardiovascular Disease in the General Population.

BACKGROUND: There are marked sex differences in cardiovascular disease (CVD) manifestation. It is largely unknown how the distribution of CVD risk factors or intermediate phenotypes explain sex-specific differences. METHODS AND RESULTS: In 5000 individuals of the population-based Gutenberg Health Study, mean age 55 ± 11 years, 51% males, we examined sex-specific associations of classical CVD risk factors with intima-media thickness, ankle-brachial index, flow-mediated dilation, peripheral arterial tonometry, echocardiographic, and electrocardiographic variables. Intermediate cardiovascular phenotypes were related to prevalent CVD [coronary artery disease, heart failure, stroke, myocardial infarction, lower extremity artery disease (LEAD) N = 561]. We observed differential distributions of CVD risk factors with a higher risk factor burden in men. Manifest coronary artery disease, stroke, myocardial infarction, and LEAD were more frequent in men; the proportion of heart failure was higher in women. Intermediate phenotypes showed clear sex differences with more beneficial values in women. Fairly linear changes toward less beneficial values with age were observed in both sexes. In multivariable-adjusted regression analyses, age, systolic blood pressure, and body mass index were consistently associated with intermediate phenotypes in both sexes with different ranking according to random forests, maximum model R(2) 0.43. Risk factor-adjusted associations with prevalent CVD showed some differences by sex. No interactions by menopausal status were observed. CONCLUSION: In a population-based cohort, we observed sex differences in risk factors and a broad range of intermediate phenotypes of non-invasive cardiovascular structure and function. Their relation to prevalent CVD differed markedly. Our results indicate the need of future investigations to understand sex differences in CVD manifestation.