Novel insights into bicuspid aortic valve (BAV) aortopathy: Long non-coding RNAs TUG1 and MIAT are differentially expressed in BAV ascending aortas.

BACKGROUND: Whilst a combination of genetically mediated vulnerability and hemodynamic insult is suspected to contribute to bicuspid aortic valve (BAV) aortopathy, the underlying pathophysiological mechanisms are poorly understood. METHODS: Utilizing RT-qPCR, we compared the expression of 28 potentially relevant long non-coding RNA (lncRNA) in aortic tissue from BAV patients undergoing aortic surgery for aortopathy, to healthy controls. Relative lncRNA expression was measured using ΔΔCT, with fold-change calculated as RQ=2-ΔΔCT. RESULTS: When comparing samples from BAV patients (n=29, males n=25; median age 58 years, Q1-Q3 51-65, maximum aortic dimension 50±5 mm) with healthy controls (n=7; males n=4, P=.12; median age 39 years, Q1-Q3 18-47, P=.001), there were two differentially expressed lncRNA: TUG1 expression was significantly lower in BAV aortic tissue (RQ 0.59, 95% CI 0.50-0.69, P=.02), whilst MIAT expression was significantly higher (RQ 2.87, 95% CI 1.96-4.20, P=.01). Sensitivity analysis including only patients with normal BAV function showed similar trends of differential expression of TUG1 (RQ 0.69, 95% CI 0.50-0.90, P=.29) and MIAT (RQ 2.55, 95% CI 1.21-5.36, P=.29) compared to controls. CONCLUSIONS: LncRNA TUG1 and MIAT are differentially expressed in BAV aortopathy compared to healthy controls, independent of BAV hemodynamics. Aberrant lncRNA expression may be involved in the pathogenesis of BAV aortopathy.

Long-term cardiovascular and noncardiovascular mortality of 1023 patients with confirmed acute pulmonary embolism.

BACKGROUND: There are currently no guidelines advising long-term surveillance of patients following an acute pulmonary embolism (PE), because long-term outcome studies are rare. We investigated the long-term cardiovascular and all-cause mortality of a large patient cohort with confirmed PE in relation to baseline cardiovascular disease (CVD). METHODS AND RESULTS: Clinical details of all patients presenting with acute PE to a tertiary hospital were retrieved from medical records, and their survival tracked from a statewide death registry. There were 1023 (45% males) patients admitted with confirmed PE from 2000 to 2007. During a mean follow-up of 3.8±2.6 years, 363 patients died (35.5%), of whom only 31 (3.0%) died in-hospital during the index PE admission. The 3-month, 6-month, 1-year, 3-year, and 5-year cumulative mortality rates were 8.3%, 11.1%, 16.3%, 26.7%, and 31.6% respectively. Annual mortality did not improve over the 7-year period. The postdischarge mortality of 8.5%/patient-year was 2.5-fold that of an age- and sex-matched general population, being 12.6-fold in the youngest quintile (<55 years) and 1.9-fold in the oldest quintile (≥83 years). Patients with known CVD at baseline had 2.2-fold greater all-cause mortality than those without CVD, and this effect, although at a lower level of risk, remained significant after multivariate analysis. Of the 332 deaths occurring postdischarge, 40% were attributed to cardiovascular causes. CONCLUSIONS: In a contemporary adult population, PE is associated with a substantially increased long-term mortality, of which nearly half is cardiovascular. Our study highlights the urgent need to develop long-term surveillance strategies in this population.

Left atrial size increases with body mass index in children.

OBJECTIVES: To evaluate the association between body mass index (BMI) z-score and left atrial (LA) size in childhood and to determine whether LA size differs between healthy weight (HW), overweight (OW) and obese (OB) children. BACKGROUND: LA enlargement is an independent risk factor for adverse cardiovascular outcomes. BMI is associated with LA size in adults but this may be mediated by co-morbidities that accompany adult obesity. Thus the relationship between LA size and BMI z-score in children is of interest, to assess the effect of increased body mass per se. METHODS: 991 children aged 5-15 years (9.3+/-2.8 years, 60% male), with normal cardiac structure and function, were studied by ultrasound. LA diameter (indexed to height) was measured and regression analysis assessed the association with possible determinants. RESULTS: Indexed LA diameter was significantly associated with BMI z-score (r=0.239), age (r=0.282), left ventricular (LV) posterior wall (LVPW) thickness (r=0.125) and LV mass index (r=0.349) (p<0.001 for all). On multivariate analysis, BMI z-score was significantly related to Indexed LA diameter after controlling for age, sex and LV mass index or LVPW thickness. Indexed LA diameter increased across weight groups [19.8+/-2.9, 20.5+/-2.8 and 21.9+/-3.3 mm/m for HW, OW and OB, respectively (p<0.001)]. CONCLUSIONS: In children, higher BMI z-score is an independent determinant of increased LA size, suggesting that obesity exerts an effect on LA size at an early age and thus potentially predisposes to later cardiovascular morbidity.