Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults.

Background: Incidence of cryptogenic ischemic stroke (CIS) in young adults is increasing. Early left atrial (LA) myopathy might be 1 of the underlying mechanisms, but this has only been scarcely explored. Objectives: The purpose of this study was to assess the association between increased LA stiffness and CIS in young adults. Methods: In the multicenter SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study, LA function was analyzed by speckle tracking echocardiography in 150 CIS patients (aged 18-49 years) and 150 age- and sex-matched controls. Minimum and maximum LA volumes, LA reservoir and contractile strain were measured. LA stiffness was calculated by the ratio: mitral peak E-wave velocity divided by mitral annular e' velocity (E/e')/LA reservoir strain and considered increased if ≥0.22. Increased LA volumes, LA stiffness, and/or reduced LA strain indicated LA myopathy. Logistic regression was used to determine the relation between LA stiffness and CIS and the clinical variables associated with LA stiffness. Results: Increased LA stiffness was found in 36% of patients and in 18% of controls (P < 0.001). Increased LA stiffness was associated with a 2.4-fold (95% CI: 1.1-5.3) higher risk of CIS after adjustment for age, sex, comorbidities, and echocardiographic confounders (P = 0.03). In patients, obesity, pre-CIS antihypertensive treatment, older age, and lower LA contractile strain were all related to increased LA stiffness (all P < 0.05). Conclusions: LA myopathy with increased LA stiffness and impaired LA mechanics more than doubles the risk of CIS in patients under the age of 50 years. This provides new insights into the link between LA dysfunction and CIS at young ages. (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome [SECRETO]; NCT01934725).

Influence of cardiorespiratory fitness on obesity-associated inflammation in women and men: The FATCOR study.

BACKGROUND AND AIMS: Cardiorespiratory fitness has been postulated to lower chronic inflammation in obesity. We assessed sex-specific associations of inflammation with cardiorespiratory fitness in overweight and obese persons. METHODS AND RESULTS: Peak oxygen uptake (VO2max) was measured by treadmill in 566 participants (age 48 ± 9 years, 60% women) with body mass index >27.0 kg/m2 in the FAT associated CardiOvasculaR dysfunction (FATCOR) study. Fitness was identified from age- and sex specific reference levels of VO2max. The inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), kynurenine:tryptophan ratio (KTR) and pyriodoxic acid ratio (PAr) were measured by mass spectrometry. In the total study population 63% had obesity and 74% were cardiorespiratory unfit. Unfit women had the highest fat percentage and the highest serum levels of CRP and SAA (p < 0.05). In multivariable linear regression analyses in women, higher CRP (ß -0.15, p = 0.001), SAA (ß -0.10, p = 0.03) and PAr (ß -0.09, p = 0.03) were associated with lower VO2max after adjusting for confounders. In multivariable analyses in men, higher PAr (ß -0.14, p = 0.02) was associated with lower VO2max. In multivariable analyses in obese women, higher CRP and PAr remained associated with lower VO2max (p < 0.05), while in obese men there was no significant association. When normalizing VO2max for fat-free mass (VO2maxFFM) higher CRP, SAA and PAr index were associated with lower VO2maxFFM in women, while only higher PAr index was associated with lower VO2maxFFM in men. CONCLUSION: The association of inflammation with lower cardiorespiratory fitness was more pronounced in women than men, in particular when obesity was present. CLINICAL TRIAL REGISTRATION: URL: http://www. CLINICALTRIALS: gov NCT02805478.

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

AIMS: 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, 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 four-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 with men despite lower MR regurgitant volumes and similar indexed LA size. The findings reveal sex-specific features of LA remodeling in MR. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04442828.

Preoperative risk factors associated with left ventricular dysfunction after bariatric surgery.

A large proportion of patients with severe obesity remain with left ventricular (LV) dysfunction after bariatric surgery. We assessed whether preoperative evaluation by echocardiography and inflammatory proteins can identify this high-risk group. In the Bariatric Surgery on the West Coast of Norway study, 75 patients (44 ± 10 years, body mass index [BMI] 41.5 ± 4.7 kg/m2) were prospectively evaluated by echocardiography and inflammatory proteins (high-sensitivity C-reactive protein [hsCRP], serum amyloid A [SAA] and calprotectin) before and one year after Roux-en-Y gastric bypass surgery. LV mechanics was assessed by the midwall shortening (MWS) and global longitudinal strain (GLS). Bariatric surgery improved BMI and GLS, and lowered hsCRP, calprotectin and SAA (p < 0.05). MWS remained unchanged and 35% of patients had impaired MWS at 1-year follow-up. A preoperative risk index including sex, hypertension, ejection fraction (EF) and high hsCRP (index 1) or SAA (index 2) predicted low 1-year MWS with 81% sensitivity/71% specificity (index 1), and 77% sensitivity/77% specificity (index 2) in ROC analyses (AUC 0.80 and 0.79, p < 0.001). Among individuals with severe obesity, women and patients with hypertension, increased serum levels of inflammatory proteins and reduced EF are at high risk of impaired LV midwall mechanics 1 year after bariatric surgery.ClinicalTrials.gov identifier NCT01533142 February 15, 2012.

Myocardial Work in Middle-Aged Adults with Overweight and Obesity: Associations with Sex and Central Arterial Stiffness.

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 (ß = 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.

Arterial Stiffness in Overweight and Obesity: Association with Sex, Age, and Blood Pressure.

INTRODUCTION: Obesity has been associated with increased arterial stiffness. Sex-differences in arterial stiffness in obesity have been less explored. AIM: To explore sex-differences in arterial stiffness by applanation tonometry in 323 women and 225 with overweight and obesity, free of cardiovascular disease. METHODS: Covariables of arterial stiffness were identified in multivariable linear regression analyses in the total cohort and separately in women and men. RESULTS: In the total study cohort, women had higher augmentation pressure (AP) and augmentation index (AIx), and lower carotid-femoral pulse wave velocity (cf-PWV) than men, independent of confounders (all p < 0.001). In sex-specific analyses, higher AP was associated with higher age and 24-hours systolic blood pressure (BP), and with lower heart rate in women (all p < 0.001), and with higher age and BP in men (all p < 0.001). Similarly, higher AIx was associated with higher age and BP, and lower body mass index (BMI) and heart rate in women (all p < 0.05), and with higher age in men (all p < 0.001). Higher cf-PWV correlated with higher age and BP in women (all p < 0.005), and additionally with higher heart rate and non-smoking in men (all p < 0.05). When replacing BMI with waist-hip ratio, higher waist-hip ratio was associated with higher cf-PWV in men only (p < 0.05). CONCLUSIONS: Among subjects with overweight and obesity, AP and AIx were higher in women, and cf-PWV was higher in men. Age and 24-hours systolic BP were the main factors associated with arterial stiffness in both sexes, while measures of adiposity had little impact on arterial stiffness.

Atrial Dysfunction in Significant Atrial Functional Mitral Regurgitation: Phenotypes and Prognostic Implications.

BACKGROUND: Atrial functional mitral regurgitation (AFMR) is associated with increased morbidity and mortality. Left atrial (LA) size and function in AFMR are poorly characterized. We aimed to assess LA function by reservoir strain (LASr) and estimated reservoir work (LAWr) and their impact on outcome in AFMR. METHODS: Consecutive patients at our institution between 2001 and 2019 and with significant (moderate or greater) AFMR were examined. LAWr was estimated as LASr×LA reservoir volume, and patients were grouped by median LASr and LAWr. Outcomes were all-cause death or heart failure hospitalizations. RESULTS: Five hundred fifteen AFMR patients were followed up for 5 (1-17) years. Patients had previously documented atrial fibrillation (AF; 37%), heart failure with preserved ejection fraction (HFpEF) without AF (24%), or both (HFpEF+AF, 39%). LA volume was largest in AF, while LA function parameters were most impaired in the combined HFpEF+AF group. During follow-up, patients with low LASr or LAWr had higher risk of death (P<0.001) and heart failure hospitalization (P<0.05). In Cox regression analyses, low LASr and LAWr, but not LA volume or left ventricular function, were associated with a higher risk of death (LASr: hazard ratio, 2.3 [95% CI, 1.6-3.5]; LAWr: hazard ratio, 3.4 [95% CI, 2.4-4.9]; both P<0.001) after adjustment for clinical and echocardiographic confounders. Low LASr and LAWr were strongest associated with death in HFpEF and HFpEF+AF. CONCLUSIONS: LA reservoir function but not LA size is a robust predictor of outcome in significant AFMR. This provides mechanistic insights into the interplay of functional versus geometric LA changes in AFMR.

Prognosis in asymptomatic patients with discordantly graded aortic valve stenosis based on pressure recovery adjusted valve area.

OBJECTIVE: We 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. METHODS: Data 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. RESULTS: DGASEL 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). CONCLUSIONS: Patients with asymptomatic AS who remain with discordant grading after adjustment for pressure recovery have increased risk for HF and death. TRIAL REGISTRATION NUMBER: NCT00092677.

Markers of Subclinical Atherosclerosis in Severe Obesity and One Year after Bariatric Surgery.

Background: Aortic valve sclerosis (AVS), mitral valve sclerosis (MVS), remodeling of major arteries, and increased pericardial fat are associated with subclinical atherosclerosis. We assessed these markers of atherosclerosis in severely obese patients before and 1 year after bariatric surgery. Methods: Eighty-seven severely obese patients (43 ± 10 years, preoperative body mass index [BMI] 41.8 ± 5 kg/m2) underwent echocardiography before and 1 year after Roux-en-Y bypass surgery in the FatWest (Bariatric Surgery on the West Coast of Norway) study. We measured the end-diastolic aortic wall thickness (AWT), pericardial fat thickness at the right ventricular free wall, and AVS/MVS based on combined aortic leaflet thickness and hyperechoic valve lesions. Results: Postoperatively, patients experienced a reduction of 12.9 ± 3.9 kg/m2 in BMI, 0.5 ± 1.9 mm in AWT, 2.6 ± 2.3 mm in pericardial fat, and 45%/53% in AVS/MVS (p < 0.05). In multivariate regression analyses with adjustment for clinical and hemodynamic variables, less pericardial fat reduction was associated with male sex and higher 1-year blood pressure and BMI, and less AWT-reduction with higher age and 1-year BMI (p < 0.05). Persistent AVS and MVS were related to higher 1-year BMI and more advanced valve sclerosis preoperatively (p < 0.05). Conclusions: Markers of subclinical atherosclerosis decreases significantly 1 year after bariatric surgery, particularly in younger patients that achieve a BMI < 28 kg/m2.

Grading of Aortic Stenosis: Is it More Complicated in Women?

Aortic stenosis (AS) is the most common valvular heart disease and the main indication for valvular replacement in older women. Correct AS grading is mandatory for an adequate selection of patients for both surgical and transcatheter aortic valve replacement. Women and men have different AS severity grades at the same level of aortic valve calcification. Moreover, besides having smaller cardiac volumes, left ventricular outflow tract and aortic size, women have a specific pattern of left ventricular structural and functional remodelling in response to the AS-related chronic pressure overload. Here, the sex-specific cardiac changes in AS that make AS grading more challenging in women, with consequences for the management and outcome of this group of patients, are reviewed.

Low myocardial energetic efficiency is associated with increased mortality in aortic stenosis.

OBJECTIVES: In 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. METHODS: Data 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. RESULTS: MEEi <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). CONCLUSIONS: In 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 NUMBER: NCT00092677.

Higher Acceleration/Ejection Time Ratio Predicts Impaired Outcome in Aortic Valve Stenosis.

BACKGROUND: Acceleration time (AT)/ejection time (ET) ratio is a marker of aortic valve stenosis (AS) severity and predicts outcome in moderate-severe AS. METHODS: We explored the association of increased AT/ET ratio on prognosis in 1530 asymptomatic patients with presumably mild-moderate AS, normal ejection fraction, and without known diabetes or cardiovascular disease. Patients were part of the SEAS study (Simvastatin Ezetimibe Aortic Stenosis). Patients were grouped according to the optimal AT/ET ratio threshold to predict cardiovascular death and heart failure hospitalization. Low-gradient severe AS was identified as combined valve area ≤1.0 cm2 and mean gradient <40 mm Hg. Outcome was assessed in Cox regression analyses, and results are reported as hazard ratio and 95% CI. RESULTS: Higher AT/ET ratio was significantly associated with lower systolic blood pressure, lower left ventricular ejection fraction, lower stress-corrected midwall shortening, low flow, and with higher left ventricular mass and higher peak aortic jet velocity. AT/ET ratio ≥0.32 provided the optimal cutoff for predicting incident cardiovascular death and heart failure hospitalization in the total study sample. In patients with low-gradient severe AS, this threshold was >0.32. AT/ET ratio ≥0.32 had a 79% higher risk of cardiovascular death and heart failure hospitalization (hazard ratio, 1.79 [95% CI, 1.20-2.68]). In patients with low-gradient severe AS, AT/ET ratio >0.32 was associated with a 2-fold higher risk of cardiovascular death and heart failure hospitalization (hazard ratio, 2.15 [95% CI, 1.22-3.77]). CONCLUSIONS: In asymptomatic nonsevere AS and low-gradient severe AS, higher AT/ET ratio was associated with increased cardiovascular morbidity and mortality. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00092677.

COVID-19 myocarditis and postinfection Bell's palsy.

Here we present the case of a 37-year-old previously healthy man who developed fever, headache and a unilateral, painful neck swelling while working offshore. He had no known contact with anyone with COVID-19; however, due to the ongoing pandemic, a nasopharyngeal swab was performed, which was positive for the virus. After transfer to hospital for assessment his condition rapidly deteriorated, requiring admission to intensive care for COVID-19 myocarditis. One week after discharge he re-presented with unilateral facial nerve palsy. Our case highlights an atypical presentation of COVID-19 and the multifaceted clinical course of this still poorly understood disease.

One-year impact of bariatric surgery on left ventricular mechanics: results from the prospective FatWest study.

Aims: Patients with severe obesity are predisposed to left ventricular (LV) hypertrophy, increased myocardial oxygen demand, and impaired myocardial mechanics. Bariatric surgery leads to rapid weight loss and improves cardiovascular risk profile. The present prospective study assesses whether LV wall mechanics improve 1 year after bariatric surgery. Methods and results: Ninety-four severely obese patients [43 ± 10 years, 71% women, body mass index (BMI) 41.8 ± 4.9 kg/m2, 57% with hypertension] underwent echocardiography before, 6 months and 1 year after gastric bypass surgery in the FatWest (Bariatric Surgery on the West Coast of Norway) study. We assessed LV mechanics by midwall shortening (MWS) and global longitudinal strain (GLS), LV power/mass as 0.222 × cardiac output × mean blood pressure (BP)/LV mass, and myocardial oxygen demand as the LV mass-wall stress-heart rate product. Surgery induced a significant reduction in BMI, heart rate, and BP (P < 0.001). Prevalence of LV hypertrophy fell from 35% to 19% 1 year after surgery (P < 0.001). The absolute value of GLS improved by-4.6% (i.e. 29% increase in GLS) while LV ejection fraction, MWS, and LV power/mass remained unchanged. In multivariate regression analyses, 1 year improvement in GLS was predicted by lower preoperative GLS, larger mean BP, and BMI reduction (all P < 0.05). Low 1-year MWS was associated with female sex, preoperative hypertension, and higher 1-year LV relative wall thickness and myocardial oxygen demand (all P < 0.001). Conclusion: In severely obese patients, LV longitudinal function is largely recovered one year after bariatric surgery due to reduced afterload. LV midwall mechanics does not improve, particularly in women and patients with persistent LV geometric abnormalities. ClinicalTrialsgov identifier: NCT01533142, 15 February 2012.

Prognostic impact of impaired left ventricular midwall function during progression of aortic stenosis.

OBJECTIVE: In hypertension, indexes of midwall left ventricular (LV) function may identify patients at higher cardiovascular (CV) risk independent of normal LV ejection fraction (EF). We analyzed the association of baseline and new-onset LV midwall dysfunction with CV outcome in a large population of patients with asymptomatic aortic stenosis (AS). METHODS: One thousand four hundred seventy-eight patients with asymptomatic AS and normal EF (≥50%) at baseline in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study were followed for a median of 4.3 years. LV systolic function was assessed by biplane EF and midwall shortening (MWS, low if <14% in men/16% in women) at baseline and annual echocardiographic examinations. RESULTS: One hundred twenty-three CV deaths and heart failure hospitalizations occurred during follow-up. In Cox analyses, adjusting for age, gender, body mass index, hypertension, EF, AS severity, LV hypertrophy and systemic arterial compliance, low baseline MWS predicted 61% higher risk of a major CV event and a twofold higher risk of death and heart failure hospitalization (P < .05). New-onset low MWS developed in 574 patients, particularly in elderly women with higher blood pressure and more severe AS (P < .05). In time-varying Cox analysis, new-onset low MWS was associated with a twofold higher risk of CV death and heart failure hospitalization, independent of changes over time in EF, AS severity, LV hypertrophy and systemic arterial compliance (P < .05). CONCLUSIONS: Low MWS develops in a large proportion of patients with AS and normal EF during valve disease progression and is a marker of increased CV risk.

Left ventricular myocardial oxygen demand and subclinical dysfunction in patients with severe obesity referred for bariatric surgery.

BACKGROUND AND AIMS: Increased myocardial oxygen (O2) demand carries higher cardiovascular risk in hypertension. We hypothesized that myocardial O2 demand is increased in severe obesity and linked to early left ventricular (LV) dysfunction. METHODS AND RESULTS: Baseline data from 106 severely obese subjects referred for gastric bypass surgery (42 ± 11 years, 74% women, body mass index [BMI] 41.9 ± 4.8 kg/m2, 32% with hypertension) in the prospective FatWest (Bariatric Surgery on the West Coast of Norway) study was used. LV systolic function was assessed by biplane ejection fraction (EF), midwall shortening (MWS) and endocardial global longitudinal strain (GLS), and LV diastolic function by mitral annular early diastolic velocity (e'). Myocardial O2 demand was estimated from the LV mass-wall stress-heart rate product (high if > 1.62 × 106/2.29 × 106 g kdyne/cm2 bpm in women/men). High myocardial O2 demand was found in 33% and associated with higher BMI and high prevalence of low GLS (65%) and low MWS (63%) despite normal EF. In ROC analyses, higher myocardial O2 demand discriminated between patients with low vs. normal MWS and GLS (area under curve 0.71 and 0.63, p < 0.05). In successive multiple regression analyses, higher myocardial O2 demand was associated with lower LV MWS, GLS and average e', respectively, independent of age, gender, BMI, pulse pressure, diabetes mellitus, and EF (all p < 0.05). CONCLUSION: In obese patients without known heart disease and with normal EF referred for bariatric surgery, high myocardial O2 demand is associated with lower myocardial function whether assessed by GLS or MWS independent of confounders. CLINICALTRIALS. GOV IDENTIFIER: NCT01533142.

Low systemic arterial compliance is associated with increased cardiovascular morbidity and mortality in aortic valve stenosis.

OBJECTIVE: Lower systemic arterial compliance (SAC) is associated with increased cardiovascular morbidity and mortality in hypertension, but this has not been assessed in a prospective study in aortic valve stenosis (AS). METHODS: Data from 1641 patients (38% women) with initially asymptomatic mild-moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study was used. Median follow-up was 4.3 years. SAC was assessed from Doppler stroke volume index to central pulse pressure ratio and considered low if ≤0.64 mL/m², corresponding to the lower tertile in the population. The association of SAC with outcome was assessed in Cox regression analysis and reported as HR and 95% CI. RESULTS: Low SAC at baseline was characterised by older age, female sex, hypertension, obesity, presence of a small aortic root, lower mean aortic gradient and more severe AS by effective aortic valve area (all p<0.01). In Cox regression analysis adjusting for factors, low SAC was associated with higher HRs for cardiovascular death (HR 2.13(95% CI 1.34 to 3.40) and all-cause mortality (HR 1.71(95% CI 1.23 to 2.38)), both p=0.001). The results did not change when systolic or diastolic blood pressure, other measures of AS severity or presence of discordantly graded AS were included in subsequent models. Presence of low SAC did not improve mortality prediction in reclassification analysis. CONCLUSIONS: In patients with AS without diabetes and known cardiovascular disease, but a high prevalence of hypertension, low SAC was associated with higher cardiovascular and all-cause mortality independent of well-known prognosticators. TRIAL REGISTRATION NUMBER: NCT00092677; Post-results.

Impact of Obesity on Persistent Left Ventricular Hypertrophy After Aortic Valve Replacement for Aortic Stenosis.

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.