Sex differences in left atrial volumes, mechanics and stiffness in primary mitral regurgitation- a combined 2D and 3D echocardiographic study.

BACKGROUND: Mitral regurgitation (MR) causes left atrial (LA) enlargement and impaired reservoir function. We assessed whether changes in LA size, strain and stiffness in significant (moderate or greater) primary MR are sex-specific. METHODS AND RESULTS: In the 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation study (3D-PRIME), 111 patients with primary MR were prospectively investigated with 2D and 3D echocardiography. MR was severe if the 3D regurgitant fraction was ≥50%. LA size was assessed by maximum, minimum and pre-A 3D volume (LAV), mechanics by peak reservoir (LASr) and contractile strain, and stiffness by the ratio: mitral peak E-wave divided by the annular e' velocity (E/e´)/LASr.Women were older, had higher heart rate, and lower body mass index and MR regurgitant volumes (p < 0.05). 3D LAV indexed for body surface area and LA contractile strain did not differ by sex, while LASr was lower (22.2% vs. 25.0%) and LA stiffness higher in women (0.56 vs. 0.44) (p < 0.05). In linear regression analysis, female sex was associated with higher LA stiffness independent of age, minimum LAV, left ventricular global longitudinal strain, diabetes and coronary artery disease (R2 0.56, all p < 0.05). In logistic regression analysis, women had a 4.0-fold (95% CI 1.2-13.1, p = 0.02) higher adjusted risk of increased LA stiffness than men. CONCLUSION: Women with significant primary MR have more impaired LA reservoir mechanics and increased LA stiffness compared to men despite lower MR regurgitant volumes and similar indexed LA size. The findings reveal sex-specific features of LA remodeling in MR.

Relation of Left Ventricular Mass to Prognosis in Initially Asymptomatic Mild to Moderate Aortic Valve Stenosis.

BACKGROUND: The prognostic importance of left ventricular (LV) mass in nonsevere asymptomatic aortic stenosis has not been documented in a large prospective study. METHODS AND RESULTS: Cox regression analysis was used to assess the impact of echocardiographic LV mass on rate of major cardiovascular events in 1656 patients (mean age, 67 years; 39.6% women) with mild-to-moderate asymptomatic aortic stenosis participating in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. Patients were followed during 4.3 years of randomized treatment with combined simvastatin 40 mg and ezetimibe 10 mg daily or placebo. At baseline, LV mass index was 45.9+14.9 g/m(2.7), and peak aortic jet velocity was 3.09+0.54 m/s. During follow-up, 558 major cardiovascular events occurred. In Cox regression analyses, 1 SD (15 g/m(2.7)) higher baseline LV mass index predicted increases in hazards of 12% for major cardiovascular events, 28% for ischemic cardiovascular events, 34% for cardiovascular mortality, and 23% for combined total mortality and hospitalization for heart failure (all P<0.01), independent of confounders. In time-varying models, taking the progressive increase in LV mass index during follow-up into account, 1 SD higher in-study LV mass index was consistently associated with 13% to 61% higher hazard for cardiovascular events (all P<0.01), independent of age, sex, body mass index, valvuloarterial impedance, LV ejection fraction and concentricity, and the presence of concomitant hypertension. CONCLUSIONS: Higher LV mass index is independently associated with increased cardiovascular morbidity and mortality during progression of aortic stenosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Sex differences in cardiovascular outcome during progression of aortic valve stenosis.

OBJECTIVE: Women with severe aortic valve stenosis (AS) have better LV systolic function and more concentric LV geometry than their male counterparts. However, sex differences in cardiovascular (CV) outcome during progression of AS have not been reported from a longitudinal prospective study. METHODS: Doppler echocardiography and CV events were recorded during a median of 4.0 years in 979 men and 632 women aged 28-86 (mean 67±10) years in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. LV systolic function was assessed by EF and midwall shortening (MWS). Study outcomes were AS-related events, ischaemic CV events and total mortality. RESULTS: The annular cumulative incidence of AS events, ischaemic CV events and death was 8.1%, 3.4% and 2.8% in women, and 8.9%, 4.4% and 2.4% in men, respectively. Women and men had similar AS progression rate whether measured by peak jet velocity, mean gradient or valve area. In multivariate analyses, female sex independently predicted less reduction in LV MWS and EF during follow-up (both p<0.05). In time-varying Cox analyses, women had a 40% lower rate of ischaemic CV events (95% CI 21% to 54%), in particular, more than 50% lower rate of stroke and coronary artery bypass grafting, and a 31% lower all-cause mortality (95% CI 1% to 51%), independent of active study treatment, age and hypertension, as well as time-varying valve area, low systolic function and abnormal LV geometry. AS event rate did not differ by sex. CONCLUSIONS: In the SEAS study, women and men had similar rates of AS progression and AS-related events. However, women had lower total mortality and ischaemic CV event rate than men independent of confounders. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT00092677.

Impact of obesity and nonobesity on grading the severity of aortic valve stenosis.

We tested the hypothesis that the disproportionate increase of body surface area in obesity may lead to the overestimation of aortic stenosis (AS) severity when the aortic valve area (AVA) is indexed (AVAI) for body surface area in 1,524 patients enrolled in the Simvastatin and Ezetimibe in AS study. Obesity was defined as a body mass index of ≥30 kg/m(2). Peak aortic jet velocity, mean aortic gradient, AVA, and energy loss (EL) did not differ, although AVAI and EL indexed (ELI) for body surface area were significantly smaller in the obese group (n = 321) compared with the nonobese (n = 1,203) group (both p <0.05). Severe AS by AVAI (<0.6 cm(2)/m(2)) but nonsevere by AVA (>1.0 cm(2); AVAI/AVA discordance) was found in 15% of the patients, whereas severe AS by ELI (<0.6 cm(2)/m(2)) but nonsevere by EL (>1.0 cm(2); ELI/EL discordance) was found in 9% of the patients. Obesity was associated with a 2.4-fold higher prevalence of AVAI/AVA discordance and a 1.6-fold higher prevalence of ELI/EL discordance. Discordant grading was also associated with male gender, larger body size, higher mean aortic gradient, and stroke volume (all p <0.05). During a median follow-up of 4.3 years, 419 patients were referred for aortic valve replacement and 177 patients died or were hospitalized because of heart failure. In the Cox regression analyses, AVAI/AVA discordance was associated with a 28% higher rate of aortic valve replacement (p <0.05) but did not predict the rate of combined death and hospitalization for heart failure. In conclusion, using AVAI and ELI for the grading of stenosis in patients with obesity may lead to overestimation of true AS severity.

Effect of overweight and obesity on cardiovascular events in asymptomatic aortic stenosis: a SEAS substudy (Simvastatin Ezetimibe in Aortic Stenosis).

OBJECTIVES: This study investigated whether overweight and obesity impacted outcome in patients with aortic valve stenosis (AS). BACKGROUND: Increased body mass index (BMI) is a strong predictor of higher cardiovascular (CV) morbidity and mortality in the general population but not among patients undergoing heart surgery. METHODS: Cardiovascular events in 1,664 patients with initially asymptomatic AS were recorded during a mean of 4.3 years of follow-up in the SEAS (Simvastatin Ezetimibe in Aortic Stenosis) study. Patients were grouped according to baseline BMI class. RESULTS: Overweight (n = 737) and obese patients (n = 334) had higher prevalence of hypertension, more abnormal left ventricular geometry, and lower stress-corrected midwall shortening throughout the study compared with normal weight patients (all p < 0.01). The AS progression rate did not differ between BMI classes. In univariate Cox regression, overweight was associated with a 17% to 22% lower rate of AS-related (p = 0.04) and ischemic CV events (p = 0.05). In multivariate analyses, adjusting for AS severity and differences in baseline characteristics, overweight had no significant influence on the rate of ischemic CV or AS-related events, whereas overweight and obesity had 46% and 67% higher rate of total mortality and 42% and 69% higher rate of combined hospital stay for heart failure and death from any cause, respectively, compared with normal weight patients (all p < 0.05). CONCLUSIONS: In patients with initially asymptomatic AS participating in the SEAS study, overweight and obesity did not influence AS progression or rate of AS-related or ischemic CV events but were both associated with increased mortality.

Retinoylserine and retinoylalanine, natural products of the moth Trichoplusia ni.

Insect cells convert vitamin A into a number of retinoids that are evolutionarily conserved with those of mammalian cells. However, insect cells also produce additional natural retinoids. Namely, two retinoic acid peptides, N-trans-retinoylserine (1) and N-trans-retinoylalanine (2), have been isolated from a cell line of the common cabbage looper, Trichoplusia ni. These are the first examples of naturally occurring retinoic acid linked to amino acids through an amide bond; the amino acid moieties are depicted in the more common l-configuration, although the absolute configuration was not determined due to the minuscule sample amount.