Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is a common genetic variant in Asians that is responsible for defective toxic aldehyde and lipid peroxidation metabolism after alcohol consumption. The extent to which low alcohol consumption may cause atrial substrates to trigger atrial fibrillation (AF) development in users with ALDH2 variants remains to be determined. We prospectively enrolled 249 ethnic Asians, including 56 non-drinkers and 193 habitual drinkers (135 (70%) as ALDH2 wild-type: GG, rs671; 58 (30%) as ALDH2 variants: G/A or A/A, rs671). Novel left atrial (LA) mechanical substrates with dynamic characteristics were assessed using a speckle-tracking algorithm and correlated to daily alcohol consumption and ALDH2 genotypes. Despite modest and comparable alcohol consumption by the habitual alcohol users (14.3 [8.3~28.6] and 12.3 [6.3~30.7] g/day for those without and with ALDH2 polymorphism, p = 0.31), there was a substantial and graded increase in the 4-HNE adduct and prolonged PR, and a reduction in novel LA mechanical parameters (including peak atrial longitudinal strain (PALS) and phasic strain rates (reservoir, conduit, and booster pump functions), p < 0.05), rather than an LA emptying fraction (LAEF) or LA volume index across non-drinkers, and in habitual drinkers without and with ALDH2 polymorphism (all p < 0.05). The presence of ALDH2 polymorphism worsened the association between increasing daily alcohol dose and LAEF, PALS, and phasic reservoir and booster functions (all P_interaction: <0.05). Binge drinking superimposed on regular alcohol use exclusively further worsened LA booster pump function compared to regular drinking without binge use (1.66 ± 0.57 vs. 1.97 ± 0.56 1/s, p = 0.001). Impaired LA booster function further independently helped to predict AF after consideration of the CHARGE-AF score (adjusted 1.68 (95% CI: 1.06–2.67), p = 0.028, per 1 z-score increment). Habitual modest alcohol consumption led to mechanical LA substrate formation in an ethnic Asian population, which was more pronounced in subjects harboring ALDH2 variants. Impaired LA booster functions may serve as a useful predictor of AF in such populations.

Epicardial adipose tissue (EAT) as a source of pro-inflammatory cytokines tightly linked to metabolic abnormalities. Data regarding the associations of EAT with adipocyte fatty acid-binding protein (A-FABP), a cytokine implicated in the cardiometabolic syndrome, might play an important part in mediating the association between EAT and cardiac structure/function in preserved ejection fraction heart failure (HFpEF). We conducted a prospective cohort study comprising 252 prospectively enrolled study participants classified as healthy (n = 40), high-risk (n = 161), or HFpEF (n = 51). EAT was assessed using echocardiography and compared between the three groups and related to A-FABP, cardiac structural/functional assessment utilizing myocardial deformations (strain/strain rates) and HF outcomes. EAT thickness was highest in participants with HFpEF (9.7 ± 1.7 mm) and those at high-risk (8.2 ± 1.5 mm) and lowest in healthy controls (6.4 ± 1.9 mm, p < 0.001). Higher EAT correlated with the presence of cardiometabolic syndrome, diabetes and renal insufficiency independent of BMI and waist circumference (p_interaction for all > 0.1), and was associated with reduced LV global longitudinal strain (GLS) and LV mass-independent systolic/diastolic strain rates (SRs/SRe) (all p < 0.05). Higher A-FABP levels were associated with greater EAT thickness (p_interaction > 0.1). Importantly, in the combined control cohort, A-FABP levels mediated the association between EAT and new onset HF. Excessive EAT is independently associated with the metabolic syndrome, renal insufficiency, and higher A-FABP levels. The association between EAT and new onset HF is mediated by A-FABP, suggesting a metabolic link between EAT and HF.

Background: Fragmented QRS (fQRS) morphology as a surrogate marker of the possible presence of myocardial scarring has been shown to confer a higher risk in patients with reduced ejection fraction heart failure. We aimed to investigate the pathophysiological correlates and prognostic implications of fQRS in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results: We consecutively studied 960 patients with HFpEF (76.4±12.7 years, men: 37.2%). fQRS was assessed using a body surface ECG during hospitalization. QRS morphology was available and classified into 3 categories among 960 subjects with HFpEF as non‐fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the 3 fQRS categories, anterior/lateral fQRS showed significantly higher B‐type natriuretic peptide/troponin levels (both P <0.001), with both the inferior and anterior/lateral fQRS HFpEF groups demonstrating a higher degree of unfavorable cardiac remodeling, greater extent of myocardial perfusion defect, and slower coronary flow phenomenon (all P <0.05). Patients with anterior/lateral fQRS HFpEF exhibited significantly altered cardiac structure/function and more impaired diastolic indices (all P <0.05). During a median of 657 days follow‐up, the presence of anterior/lateral fQRS conferred a doubled HF re‐admission risk (adjusted hazard ratio 1.90, P <0.001), with both inferior and anterior/lateral fQRS having a higher risk of cardiovascular and all‐cause death (all P <0.05) by using Cox regression models. Conclusions: The presence of fQRS in HFpEF was associated with more extensive myocardial perfusion defects and worsened mechanics, which possibly denotes a more severe involvement of cardiac damage. Early recognition in such patients with HFpEF likely benefits from targeted therapeutic interventions.

The recently revised 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension (HTN) guidelines employ a lower blood pressure threshold to define HTN, aiming for earlier prevention of HTN-related cardiovascular diseases (CVD). Thoracic aortic calcification (TAC), a new surrogate marker of aging and aortic medial layer degeneration, and different stages of HTN, according to the 2017 ACC/AHA HTN guidelines, remain unknown. We classified 3022 consecutive asymptomatic individuals enrolled into four HTN categories using the revised 2017 ACC/AHA guidelines: normal blood pressure (NBP), elevated blood pressure (EBP), and stage 1 (S1) and stage 2 (S2) HTN. The coronary artery calcification score and TAC metrics (total Agaston TAC score, total plaque volume (mm³), and mean density (Hounsfield units, HU)) were measured using multi-detector computed tomography. Compared to NBP, a graded and significant increase in the TAC metrics was observed starting from EBP and S1 and S2 HTN, using the new 2017 ACC/AHA guidelines (NBP as reference; all trends: p < 0.001). These differences remained consistent after being fully adjusted. Older age (>50 years), S1 and S2 HTN, prevalent diabetes, and chronic kidney disease (<60 mL/min/1.73 m²) are all independently contributing factors to higher TAC risk using multivariate stepwise logistic regressions (all p ≤ 0.001). The optimal cutoff values of systolic blood pressure, diastolic blood pressure, and pulse pressure were 121, 74, and 45 mmHg, respectively, for the presence of TAC after excluding subjects with known CVD and ongoing HTN medication treatment. Our data showed that the presence of TAC starts at a stage of elevated blood pressure not categorized as HTN from the updated 2017 ACC/AHA hypertension guidelines.

Background: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) commonly coexist with overlapping pathophysiology like left atrial (LA) remodeling, which might differ given different underlying mechanisms.Objectives: We sought to investigate the different patterns of LA wall remodeling in AF vs. HFpEF.Methods: We compared LA wall characteristics including wall volume (LAWV), wall thickness (LAWT), and wall thickness heterogeneity (LAWT[SD]) and LA structure, function among the controls (without AF or HFpEF, n = 115), HFpEF alone (n = 59), AF alone (n = 37), and HFpEF+AF (n = 38) groups using multi-detector computed tomography and echocardiography.Results: LA wall remodeling was most predominant and peak atrial longitudinal strain (PALS) was worst in HFpEF+AF patients as compared to the rest. Despite lower E/e' (9.8 ± 3.8 vs. 13.4 ± 6.4) yet comparable LA volume, LAWT and PALS in AF alone vs. HFpEF alone, LAWV [12.6 (11.6–15.3) vs. 12.0 (10.2–13.7); p = 0.01] and LAWT(SD) [0.68 (0.61–0.71) vs. 0.60 (0.56–0.65); p < 0.001] were significantly greater in AF alone vs. HFpEF alone even after multi-variate adjustment and propensity matching. After excluding the HFpEF+AF group, both LAWV and LAWT [SD] provided incremental values when added to PALS or LAVi (all p for net reclassification improvement <0.05) in discriminating AF alone, with LAWT[SD] yielding the largest C-statistic (0.78, 95% CI: 0.70–0.86) among all LA wall indices.Conclusions: Despite a similar extent of LA enlargement and dysfunction in HFpEF vs. AF alone, larger LAWV and LAWT [SD] can distinguish AF from HFpEF alone, suggesting the distinct underlying pathophysiological mechanism of LA remodeling in AF vs. HFpEF.

Obesity has been conceptualized as a highly heterogeneous condition. We aim to investigate chamber-specific effects of obesity on the heart and relevant outcomes. A total of 2944 symptom-free individuals (age: 47.5 ± 10.0 years), free of known cardiovascular diseases were classified into four categories based on body mass index (BMI) (as normal-weight (NW) vs. overweight/obese (O)) and metabolic status (metabolically-healthy (MH) vs. unhealthy (MU)). Epicardial adipose thickness (EAT) using echocardiography method. Speckle-tracking based atrio-ventricular (LA/LV) deformations including global longitudinal strain (GLS) and peak atrial longitudinal strain (PALS) were also analyzed. MUNW had higher cardiometabolic risks and more impaired diastolic and GLS/PALS than MHNW phenotype. Both MHO and MUO phenotypes exhibited worst atrial functions. Greater EAT was independently associated with worse GLS and PALS after correcting for various anthropometrics, LV mass and LA volume, respectively, with unfavorable LA effects from EAT being more pronounced in the NW phenotypes (both p interactions < 0.05). During a median follow-up period of 5.3 years, BMI/EAT improved the reclassification for atrial fibrillation (AF) incidence (p for net reclassification improvement < 0.05) mainly in the NW phenotypes (p interaction < 0.001). Categorization of clinical obesity phenotypes based on excessive visceral adiposity likely provides increment prognostic impacts on atrial dysfunction, particularly in non-obese phenotypes.