Metabolomic Profiling in Relation to New-Onset Atrial Fibrillation (from the Framingham Heart Study)

Previous studies have shown several metabolic biomarkers to be associated with prevalent and incident atrial fibrillation (AF), but the results have not been replicated. We investigated metabolite profiles of 2,458 European ancestry participants from the Framingham Heart Study without AF at the index examination and followed them for 10 years for new-onset AF. Amino acids, organic acids, lipids, and other plasma metabolites were profiled by liquid chromatography-tandem mass spectrometry using fasting plasma samples. We conducted Cox proportional hazard analyses for association between metabolites and new-onset AF. We performed hypothesis-generating analysis to identify novel metabolites and hypothesis-testing analysis to confirm the previously reported associations between metabolites and AF. Mean age was 55.1 +/- 9.9 years, and 53% were women. Incident AF developed in 156 participants (6.3%) in 10 years of follow-up. A total of 217 metabolites were examined, consisting of 54 positively charged metabolites, 59 negatively charged metabolites, and 104 lipids. None of the 217 metabolites met our a priori specified Bonferroni corrected level of significance in the multivariate analyses. We were unable to replicate previous results demonstrating associations between metabolites that we had measured and AF. In conclusion, in our metabolomics approach, none of the metabolites we tested were significantly associated with the risk of future AF

Epicardial Adipose Tissue and Invasive Hemodynamics in Heart Failure With Preserved Ejection Fraction

Objectives: This study examined associations between epicardial adipose tissue (EAT), invasive hemodynamics, and exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). Background: EAT is increased in patients with HFpEF and may play a role in the pathophysiology of this disorder. Methods: Patients with heart failure and a left ventricular ejection fraction >45% who underwent right and left heart catheterization with simultaneous echocardiography were included. Pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP), right ventricular end-diastolic pressure (RVEDP), and pulmonary vascular resistance (PVR) were invasively measured. Obesity was defined as body mass index (BMI) ≥30 kg/m2. EAT thickness alongside the right ventricle was measured on echocardiographic long- and short-axis views. Cardiopulmonary exercise testing was performed to obtain maximal oxygen uptake (VO2-max). Results: This study examined 75 patients, mean age 74 ± 9 years; 68% were women, mean BMI was 29 ± 6 kg/m2, and 36% were obese. Higher BMI was strongly associated with increased EAT (r = 0.74; p < 0.001). Increased EAT was associated with higher RVEDP, independent of PVR (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.02 to 1.34; p = 0.03), but not independent of obesity (p = 0.10). Increased EAT and higher RVEDP were both associated with lower VO2-max (r = −0.43; p < 0.001 and r = −0.43; p = 0.001, respectively). Increased EAT remained associated with lower VO2-max after adjustment for PVR (OR: 0.64; 95% CI: 0.49 to 0.84; p = 0.002) and obesity (OR: 0.69; 95% CI: 0.53 to 0.92; p = 0.01). EAT thickness was not associated with left-sided filling pressures (i.e., PCWP and LVEDP). Conclusions: In HFpEF, obesity and increased EAT were associated with higher right-sided filling pressures and with reduced exercise capacity

Atrial fibrillation without comorbidities: Prevalence, incidence and prognosis (from the Framingham Heart Study)

BACKGROUND: The epidemiology of atrial fibrillation (AF) without comorbidities, known as \u27lone AF\u27, is uncertain. Although it has been considered a benign condition, we hypothesized that it confers a worse prognosis compared with a matched sample without AF. METHODS: We described the proportion of AF without comorbidities (clinical, subclinical cardiovascular disease and triggers) among the entire AF sample in Framingham Heart Study (FHS). We compared AF without comorbidities with typical AF, and age-, sex- and cohort-matched individuals without AF, using Cox proportional hazards analysis in relation to combined cardiovascular events (stroke, heart failure, myocardial infarction), and mortality. RESULTS: Of 10,311 FHS participants, 1,961 were diagnosed with incident AF, among which 173 individuals had AF without comorbidities (47% women, mean age 71+/-12 years). AF without comorbidities had a prevalence of 1.7% of the entire cohort, and an annual incidence of 0.5 per 1000 person-years. During a median follow-up of 9.7 years after initial AF, 137 individuals with AF without comorbidities (79.2%) died and 141 individuals developed cardiovascular events (81.5%). AF without comorbidities had significantly lower mortality (HR 0.67, 95%CI 0.55-0.81, P \u3c .001) and total cardiovascular events (HR 0.66, 95% CI 0.55-0.80, P \u3c .001) compared with typical AF. However, mortality (HR1.43, 95% CI 1.18-1.75, P \u3c .001) and risk of total cardiovascular events (HR 1.73, 95% CI 1.39-2.16, P \u3c .001) were higher than age-, sex-, and cohort-matched individuals without AF. CONCLUSIONS: The risk of cardiovascular outcomes and mortality among individuals with AF without comorbidities is lower than typical AF, but is significantly elevated compared with matched individuals without AF

Chronic obstructive pulmonary disease and atrial fibrillation:an interdisciplinary perspective

Chronic obstructive pulmonary disease (COPD) is highly prevalent among patients with atrial fibrillation (AF), shares common risk factors, and adds to the overall morbidity and mortality in this population. Additionally, it may promote AF and impair treatment efficacy. The prevalence of COPD in AF patients is high and is estimated to be ∼25%. Diagnosis and treatment of COPD in AF patients requires a close interdisciplinary collaboration between the electrophysiologist/cardiologist and pulmonologist. Differential diagnosis may be challenging, especially in elderly and smoking patients complaining of unspecific symptoms such as dyspnoea and fatigue. Routine evaluation of lung function and determination of natriuretic peptides and echocardiography may be reasonable to detect COPD and heart failure as contributing causes of dyspnoea. Acute exacerbation of COPD transiently increases AF risk due to hypoxia-mediated mechanisms, inflammation, increased use of beta-2 agonists, and autonomic changes. Observational data suggest that COPD promotes AF progression, increases AF recurrence after cardioversion, and reduces the efficacy of catheter-based antiarrhythmic therapy. However, it remains unclear whether treatment of COPD improves AF outcomes and which metric should be used to determine COPD severity and guide treatment in AF patients. Data from non-randomized studies suggest that COPD is associated with increased AF recurrence after electrical cardioversion and catheter ablation. Future prospective cohort studies in AF patients are needed to confirm the relationship between COPD and AF, the benefits of treatment of either COPD or AF in this population, and to clarify the need and cost-effectiveness of routine COPD screening

Dose-limiting, adverse event-associated bradycardia with β-blocker treatment of atrial fibrillation in the GENETIC-AF trial

Background: Heart failure (HF) patients with atrial fibrillation (AF) often have conduction system disorders, which may be worsened by β-blocker therapy.Objective: In a post hoc analysis we examined the prevalence of bradycardia and its association with adverse events (AEs) and failure to achieve target dose in the GENETIC-AF trial.Methods: Patients randomized to metoprolol (n = 125) or bucindolol (n = 131) entering 24-week efficacy follow-up and receiving study medication were evaluated. Bradycardia was defined as an electrocardiogram (ECG) heart rate (HR) &lt;60 beats per minute (bpm) and severe bradycardia &lt;50 bpm.Results: Mean HR in sinus rhythm (SR) was 62.6 ± 12.5 bpm for metoprolol and 68.3 ± 11.1 bpm for bucindolol (P &lt; .0001), but in AF HRs were not different (87.5 bpm vs 89.7 bpm, respectively). Episodes per patient for bucindolol vs metoprolol were 0.82 vs 2.08 (P &lt; .001) for bradycardia and 0.24 vs 0.57 for severe bradycardia (P &lt; .001), with 98.9% of the episodes occurring in SR. Patients experiencing bradycardia had a 4.15-fold higher prevalence of study medication dose reduction (P &lt;.0001) compared to patients without bradycardia. Fewer patients receiving metoprolol were at target dose (61.7% vs 74.9% for bucindolol, P &lt; .0001) at ECG recordings, and bradycardia AEs were more prevalent in the metoprolol group (13 vs 1 for bucindolol, P = .001). On multivariate analysis of 21 candidate bradycardia predictors including presence of a device with pacing capability, bucindolol treatment was associated with the greatest degree of prevention (Zodds ratio -4.24, P &lt; .0001).Conclusion: In AF-prone HF patients bradycardia may limit the effectiveness of β blockers, and this property is agent-dependent.</p

Ethnic differences in atrial fibrillation among patients with heart failure in Asia

Aims We aimed to characterize ethnic differences in prevalence, clinical correlates, and outcomes of atrial fibrillation (AF) in heart failure (HF) with preserved and reduced ejection fraction (HFpEF and HFrEF) across Asia. Methods and results Among 5504 patients with HF prospectively recruited across 11 Asian regions using identical protocols in the Asian Sudden Cardiac Death in Heart Failure study (mean age 61 +/- 13 years, 27% women, 83% HFrEF), 1383 (25%) had AF defined as a history of AF and/or AF/flutter on baseline electrocardiogram. Clinical correlates of AF were similar across ethnicities and included older age, prior stroke, higher NT-proBNP, and larger left atria. Diabetes was associated with lower odds of AF in HFrEF [adjusted odds ratio (AOR) 0.79, 95% CI 0.66-0.95] and HFpEF (AOR 0.58, 95% CI 0.39-0.84) regardless of ethnicity. Compared with Chinese ethnicity, Japanese/Koreans had higher odds of AF in HFrEF (AOR 1.76, 95% CI 1.40-2.21), while Indians had lower odds in HFrEF (AOR 0.18, 95% CI 0.13-0.24) and HFpEF (AOR 0.28, 95% CI 0.16-0.49) even after adjusting for clinical covariates. Interaction between ethnicity and region was observed among Indians, with Southeast Asian Indians having higher odds of AF (AOR 3.01, 95% CI 1.60-5.67) compared with South Asian Indians. AF was associated with poorer quality of life and increased risk of 1 year all-cause mortality or HF hospitalisation (adjusted hazard ratio 1.39, 95% CI 1.18-1.63) regardless of ethnicity. Conclusions Among patients with HF across Asia, clinical correlates and adverse outcomes associated with AF are similar across ethnicities; however, there are striking ethnic variations in the prevalence of AF that are not accounted for by known risk factors

Diabetes Mellitus and Right Ventricular Dysfunction in Heart Failure With Preserved Ejection Fraction

Diabetes mellitus is associated with left-sided myocardial remodeling in heart failure with preserved ejection fraction (HFpEF). Little is known about the impact of diabetes mellitus on right ventricular (RV) function in HFpEF. We therefore studied the relation between diabetes mellitus and RV dysfunction in HFpEF. We have examined patients with HFpEF who underwent simultaneous right-sided cardiac catheterization and echocardiography. RV systolic function was assessed using multiple established echocardiographic parameters, and systolic dysfunction was present if parameters were outside the normal range. RV diastolic function was assessed using the peak diastolic tissue velocity of the lateral tricuspid annulus (RV e') and was present if = 7.0 mmol/L, a positive glucose intolerance test result, or a glycated hemoglobin level of >= 6.5%. A total of 91 patients were studied (mean age 74 +/- 9 years, 69% women). A total of 37% had RV systolic dysfunction and 23% RV diastolic dysfunction. Thirty-seven percent of the patients had type 2 diabetes mellitus. These patients had higher pulmonary artery pressure (34 mm Hg vs 29 mm Hg, p = 0.004), more RV systolic dysfunction (57% vs 29%, p = 0.009), more RV diastolic dysfunction (46% vs 12%, p = 0.001), and lower RV e' (8.7 cm/s vs 11.5 cm/s, p = 0.006). The presence of diabetes mellitus was independently associated with RV systolic dysfunction (odds ratio 2.84, 95% confidence interval 1.09 to 7.40, p = 0.03) and with RV diastolic dysfunction (odds ratio 4.33, 95% confidence interval 1.25 to 15.07, p = 0.02), after adjustment for age, gender, and pulmonary pressures. In conclusion, diabetes mellitus is strongly associated with RV systolic and diastolic dysfunctions in patients with HFpEF, independent of RV afterload. (C) 2017 Elsevier Inc. All rights reserved