Wai Hong Tang

Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension

Background New 2-dimensional strain echocardiography enables quantification of right ventricular (RV) mechanics by assessing global longitudinal strain of RV (GLSRV) in patients with pulmonary arterial hypertension (PAH). However, the prognostic significance of impaired GLSRV is unclear in these patients. Methods Comprehensive echocardiography was performed in 51 consecutive PAH patients without atrial fibrillation (40 females, 48 ± 14 years old) with long-term follow-up. GLSRV was measured with off-line with velocity vector imaging (VVI, Siemens Medical System, Mountain View, CA, USA). Results GLSRV showed significant correlation with RV fractional area change (r = -0.606, p < 0.001), tricuspid annular plane systolic excursion (r = -0.579, p < 0.001), and RV Tei index (r = 0.590, p < 0.001). It showed significant correlations with pulmonary vascular resistance (r = 0.469, p = 0.001) and B-natriuretic peptide concentration (r = 0.351, p = 0.012). During a clinical followup time (45 ± 15 months), 20 patients experienced one or more adverse events (12 death, 2 lung transplantation, and 15 heart failure hospitalization). After multivariate analysis, age [hazard ratio (HR) = 2.343, p = 0.040] and GLSRV (HR = 2.122, p = 0.040) were associated with adverse clinical events. Age (HR = 3.200, p = 0.016) and GLSRV (HR = 2.090, p = 0.042) were also significant predictors of death. Impaired GLSRV (≥ -15.5%) was associated with lower event-free survival (HR = 4.906, p = 0.001) and increased mortality (HR = 8.842, p = 0.005). Conclusion GLSRV by VVI showed significant correlations with conventional echocardiographic parameters indicating RV systolic function. Lower GLSRV (≥ -15.5%) was significantly associated with presence of adverse clinical events and deaths in PAH patients.

Bayesian integration of genetics and epigenetics detects causal regulatory SNPs underlying expression variability

The standard expression quantitative trait loci (eQTL) detects polymorphisms associated with gene expression without revealing causality. We introduce a coupled Bayesian regression approach—eQTeL, which leverages epigenetic data to estimate regulatory and gene interaction potential, and identifies combination of regulatory single-nucleotide polymorphisms (SNPs) that explain the gene expression variance. On human heart data, eQTeL not only explains a significantly greater proportion of expression variance but also predicts gene expression more accurately than other methods. Based on realistic simulated data, we demonstrate that eQTeL accurately detects causal regulatory SNPs, including those with small effect sizes. Using various functional data, we show that SNPs detected by eQTeL are enriched for allele-specific protein binding and histone modifications, which potentially disrupt binding of core cardiac transcription factors and are spatially proximal to their target. eQTeL SNPs capture a substantial proportion of genetic determinants of expression variance and we estimate that 58% of these SNPs are putatively causal.

HEMODYNAMIC DETERMINANTS OF SERUM CHLORIDE IN AMBULATORY PATIENTS WITH ADVANCED HEART FAILURE

Lower serum chloride (Cl) is associated with mortality in patients with heart failure and may be more prognostically relevant than sodium. However, the association of hemodynamics and Cl levels is unknown. 436 sequential patients with advanced chronic heart failure (ACHF) underwent invasive

TWO-THIRDS OF HEART FAILURE PATIENTS WHO MEET THE FDA-APPROVED INDICATION FOR SACUBITRIL/VALSARTAN DO NOT MEET PARADIGM-HF ENROLLMENT CRITERIA AFTER RECENT HOSPITALIZATION

The angiotensin-neprilysin inhibitor sacubitril/valsartan was approved by FDA for NYHA FC II-IV chronic heart failure (HF) patients with reduced ejection fraction (HFrEF) based on the PARADIGM-HF trial, which excluded patients with low GFR, low baseline BP, and ACE inhibitor (ACE-I) and beta blocker

HIGHER PLASMA TRIMETHYLAMINE-N-OXIDE IS ASSOCIATED WITH GREATER ATHEROSCLEROTIC BURDEN QUANTIFIED BY THE SYNTAX SCORE

Trimethylamine-N-oxide (TMAO), a gut microbiota metabolite from dietary of phosphatidylcholine, shows a mechanistic link to coronary artery disease (CAD) pathogenesis and adverse outcomes. We aimed to examine the relationship between fasting plasma TMAO levels and the complexity and burden of CAD.

ELEVATED PLASMA TRIMETHYLAMINE-N-OXIDE IS ASSOCIATED WITH POOR PROGNOSIS IN PATIENTS WITH PERIPHERAL ARTERY DISEASE

Production of trimethylamine-N-oxide (TMAO) by gut-microbiota metabolite from dietary phosphatidylcholine has been associated with the development of atherosclerosis in animals and in humans. The ability of plasma TMAO to predict future risk of major adverse cardiac events (MACE=death, myocardial

INTRAVASCULAR VOLUME EXPANSION IN PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION IS NOT REVEALED BY CHANGES IN CARDIAC FILLING PRESSURES

Background: Volume overload and increased cardiac filling pressures are hallmark features of heart failure. This study investigates the relationship between intravascular volume and cardiac filling pressures in heart failure with reduced ejection fraction (HFREF), in which the transition from

THE ASSOCIATION OF THICK LEFT VENTRICULAR HYPERTROPHY WITH CARDIOVASCULAR OUTCOMES IN HEART FAILURE WITH PRESERVED EJECTION FRACTION: INSIGHTS FROM THE TOPCAT TRIAL

Background: In the general population, a 4-tiered classification of left ventricular hypertrophy (LVH), which accounts for the presence of left ventricular (LV) dilation in addition to increased relative wall thickness (RWT), provided additional prognostic information beyond the conventional 2-

IDENTIFYING NON-HEART FAILURE PATIENTS WITH ELEVATED NT-PROBNP LEVELS IN THE OUTPATIENT SETTING: OPPORTUNITIES FOR PREVENTION

Background: Elevated NTproBNP has been associated with adverse outcomes in the community setting for at risk (Stage A Heart failure [HF]) patients. A recent study (STOP-HF) has implied potential mortality benefits of ACE inhibitors (ACEI)/ARBs or beta blockers (BB) in this population. We

THE HOSPITAL READMISSION MODEL POORLY PREDICTS 30-DAY REHOSPITALIZATION IN HEART FAILURE

Background: Accurately predicting risk for 30-day readmission after hospital discharge remains challenging in heart failure (HF) patients. The HOSPITAL readmission model, which predicts readmission risk based upon clinical variables, has been derived and validated in general and subspecialty medical