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Normalization of left ventricular (LV) hypertrophy is expected after successful aortic valve replacement (AVR) in patients with aortic valve stenosis (AS), but is not always observed. We tested the impact of body mass index (BMI) ≥30 kg/m2 on persistent post-AVR LV hypertrophy. In the present subanalysis of Simvastatin Ezetimibe in Aortic Stenosis study, clinical and echocardiographic data of 399 patients with severe AS who underwent surgical AVR were analyzed. All patients had a standardized pre- and post-AVR echocardiogram. Patients were grouped by BMI categories into BMI <25 kg/m2, BMI 25 to 29.9 kg/m2, and BMI ≥30 kg/m2. LV hypertrophy was defined as LV mass/height2.7 >49.2 g/m2.7 in men and >46.7 g/m2.7 in women. Predictors of persistent LV hypertrophy after AVR were identified in logistic regression analysis. After a median follow-up of 196 days after AVR, LV hypertrophy was more prevalent in patients with BMI ≥30 kg/m2 compared with those with BMI 25 to 29.9 kg/m2 and those patients with BMI <25 kg/m2 (71% vs 47% and 37%, p <0.01). BMI ≥30 kg/m2 patients also remained with lower LV midwall shortening post-AVR compared with patients with normal weight (p <0.01), independent of patient prosthesis mismatch. In multivariable logistic regression analysis, the presence of BMI ≥30 kg/m2 before AVR was associated with an almost fourfold higher prevalence of post-AVR LV hypertrophy independent of significant associations with higher systolic blood pressure and lower LV midwall shortening preoperatively (odds ratio 3.75 [95% confidence interval 2.04 to 6.91], p <0.001). In conclusion, the presence of BMI ≥30 kg/m2 before AVR in patients with severe AS was strongly and independently associated with persistent post-AVR LV hypertrophy.

Asymmetric interventricular septum hypertrophy (ASH) has been associated with increased perioperative morbidity and mortality in patients with severe, symptomatic aortic valve stenosis (AS). Less is known about the prognostic impact of ASH during progression of AS. Clinical, echocardiographic, and outcome data from 1,691 patients with initially asymptomatic, mostly moderate AS, participating in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study was used. ASH was considered present if interventricular septum/posterior wall thickness ratio in end-diastole ≥1.5. The associations of ASH with hazard rate of ischemic cardiovascular events were tested in time-dependent Cox regression analyses. Based on the presence of ASH at study echocardiograms, the study population was grouped in to a no-ASH, nonpersistent ASH, persistent ASH, and new-onset ASH groups. During a median of 4.3 years of follow-up, ASH persisted or developed in 17% of patients. Persistent or new-onset ASH was characterized by higher left ventricular mass index and ejection fraction at baseline (both p <0.05) but not with female gender or hypertension. In time-varying Cox regression analyses adjusting for these confounders, persistent or new-onset ASH was associated with higher hazard rate of ischemic cardiovascular events (hazard rate 1.45; 95% confidence interval 1.09 to 1.91, p = 0.01), in particular coronary artery bypass grafting (hazard rate 1.69; 95% confidence interval 1.17 to 2.47; p = 0.006), whereas no association with increased mortality was found. In conclusion, in patients with AS without diabetes or known renal or cardiovascular disease participating in the SEAS study, persistent or new-onset ASH during progression of AS was associated with higher rate of ischemic cardiovascular events.

ObjectivesIn hypertension, low myocardial energetic efficiency (MEEi) has been documented as an integrated marker of metabolic and left ventricular (LV) myocardial dysfunction. We tested the predictive performance of MEEi in initially asymptomatic aortic stenosis (AS) patients free from diabetes and known cardiovascular disease.MethodsData from 1703 patients with mostly moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study followed for 4.3 years was used. MEE was calculated from Doppler stroke volume/([heart rate/60]) and indexed to LV mass (MEEi). The threshold value for MEEi associated with increased mortality was identified in generalised additive model with smoothing splines. Covariables of MEEi were identified in logistic regression analysis. Outcome was assessed in Cox regression analysis and reported as HR and 95% CI.ResultsMEEi <0.34 mL/s per gram was associated with increased cardiovascular mortality (n=80) (HR 2.53 (95% CI 1.50 to 4.28)) and all-cause mortality (n=155) (HR 1.74 (95% CI 1.20 to 2.52)) (both p<0.01). The association was independent of confounders of low MEEI (<0.34 mL/s per gram) identified in multivariable logistic regression analysis, including more severe AS, higher body mass index, lower LV midwall shortening and ejection fraction and presence of hypertension. Comparison of the Cox models with and without MEEi among the covariables demonstrated that MEEi significantly improved the prognostic yield (both p<0.01).ConclusionsIn patients with initially asymptomatic AS, low MEEi was associated with clustering of cardiometabolic risk factors, lower LV myocardial function and subsequent increased mortality during 4.3 years follow-up, independent of known prognosticators.Trial registration numberNCT00092677.

ObjectiveWe hypothesised that patients with asymptomatic aortic stenosis (AS) who remain with discordantly graded aortic valve stenosis (DGAS) after adjustment for pressure recovery in the aortic root represents a subgroup of patients with increased cardiovascular risk.MethodsData from 1353 patients with asymptomatic mild–moderate AS and preserved left ventricular ejection fraction enrolled in the Simvastatin and Ezetimibe in AS study was used. DGAS was identified as combined pressure adjusted valve area (energy loss) <1.0 cm² and mean aortic gradient<40 mm Hg (DGASEL). Outcome was assessed in Cox regression analysis and reported as HR and 95% CI.ResultsDGASEL was found in 196 (14.5%) patients at baseline, and was associated with older age, female sex, smaller aortic annulus diameter, lower heart rate, more extensive valve calcification and low flow (all p<0.05). In Cox regression analysis, DGASEL was associated with higher rate of heart failure (HF) hospitalisation (HR 3.31 (95% CI 1.54 to 7.09)), cardiovascular death (HR 2.63 (95% CI 1.34 to 5.17)) and all-cause mortality (HR 1.73 (95% CI 1.04 to 2.87)) independent of confounders including low flow and aortic valve calcification (all p<0.05).ConclusionsPatients with asymptomatic AS who remain with discordant grading after adjustment for pressure recovery have increased risk for HF and death.Trial registration numberNCT00092677.

ObjectiveSex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS).MethodsAVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account.ResultsMore men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women.ConclusionIn conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men.Trial registration numberClinicalTrials.gov identifier: NCT00092677

We explored global myocardial work index (GWI), a novel measure of myocardial function that integrates left ventricular (LV) hemodynamic load, in relation to sex and increased body mass index (BMI). We used data from 467 individuals (61% women, average age 47 ± 9 years and BMI 31.2 kg/m2) without known cardiac disease. Central arterial function was analysed by applanation tonometry. GWI was calculated from global longitudinal strain (GLS) and post-echocardiography supine blood pressure (BP). Covariables of GWI were identified in linear regression analyses. Women had higher BMI, aortic augmentation pressure (12 ± 7 vs. 8 ± 6 mmHg), LV GLS (20.0 ± 2.8 vs. 18.8 ± 2.8%), and GWI (2126 ± 385 vs. 2047 ± 389 mmHg%) than men (all p < 0.05). In univariable analyses, higher GWI was associated with female sex, higher age, systolic BP, LV wall stress, LV ejection fraction, left atrial size, LV ejection time, and with lower waist circumference (all p < 0.05). In multivariable analysis, adjusting for these correlates, female sex remained independently associated with higher GWI (β = 0.13, p = 0.007). After additional adjustment for aortic augmentation pressure or central pulse pressure, this association became non-significant. In conclusion, the higher GWI in women compared to men was mainly explained by increased LV workload due to higher aortic augmentation pressure in women.

ObjectiveWhether increased myocardial oxygen demand could help explain the association of left ventricular (LV) hypertrophy with higher adverse event rate in patients with aortic valve stenosis (AS) is unknown.MethodsData from 1522 patients with asymptomatic mostly moderate AS participating in the Simvastatin-Ezetimibe in AS study followed for a median of 4.3 years was used. High LV mass–wall stress–heart rate product was identified as >upper 95% CI limit in normal subjects. The association of higher LV mass–wall stress–heart rate product with major cardiovascular (CV) events, combined CV death and hospitalised heart failure and all-cause mortality was tested in Cox regression analyses, and reported as HR and 95% CI.ResultsHigh LV mass–wall stress–heart rate product was found in 19% at baseline, and associated with male sex, higher body mass index, hypertension, LV hypertrophy, more severe AS and lower LV ejection fraction (all p<0.01). Adjusting for these confounders in time-varying Cox regression analysis, 1 SD higher LV mass–wall stress–heart rate product was associated with higher HR of major CV events (HR 1.16(95% CI 1.06 to 1.29)), combined CV death and hospitalised heart failure (HR 1.29(95% CI 1.09 to 1.54)) and all-cause mortality (HR 1.34(95% CI 1.13 to 1.58), all p<0.01).ConclusionIn patients with initially mild–moderate AS, higher LV mass–wall stress–heart rate product was associated with higher mortality and heart failure hospitalisation. Our results suggest that higher myocardial oxygen demand is contributing to the higher adverse event rate reported in AS patients with LV hypertrophy.Trial registration number NCT000092677;Post-results.