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).

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.

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.

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.

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.

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.