Erick Avelar

Left Ventricular Hypertrophy in Severe Obesity: Interactions Among Blood Pressure, Nocturnal Hypoxemia, and Body Mass

Obese subjects have a high prevalence of left ventricular (LV) hypertrophy. It is unclear to what extent LV hypertrophy results directly from obesity or from associated conditions, such as hypertension, impaired glucose homeostasis, or obstructive sleep apnea. We tested the hypothesis that LV hypertrophy in severe obesity is associated with additive effects from each of the major comorbidities. Echocardiography and laboratory testing were performed in 455 severely obese subjects with body mass index 35 to 92 kg/m2 and 59 nonobese reference subjects. LV hypertrophy, defined by allometrically corrected (LV mass/height2.7), gender-specific criteria, was present in 78% of the obese subjects. Multivariable regression analyses showed that average nocturnal oxygen saturation <85% was the strongest independent predictor of LV hypertrophy (P<0.001), followed by systolic blood pressure (P<0.015) and then body mass index (P<0.05). With regard to LV mass, there were synergistic effects between hypertension and body mass index (P interaction <0.001) and between hypertension and reduced nocturnal oxygen saturation. Severely obese subjects had normal LV endocardial fractional shortening (35±6% versus 35±6%) but mildly decreased midwall fractional shortening (15±2% versus 17±2%; P<0.001), indicating subtle myocardial dysfunction. In conclusion, more severe nocturnal hypoxemia, increasing systolic blood pressure, and body mass index are all independently associated with increased LV mass. The effects of increased blood pressure seem to amplify those of sleep apnea and more severe obesity.

Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese

Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight‐loss intervention. Three groups of severely obese subjects (N = 1,156, BMI ≥ 35 kg/m2) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population‐based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes‐related variables, resting metabolic rate (RMR), sleep apnea, and health‐related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF‐36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux‐en‐Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight‐loss intervention was highly effective for weight loss, improved health‐related quality of life, and resolution of major obesity‐associated complications measured at 2 years.

Impaired insulin signaling accelerates cardiac mitochondrial dysfunction after myocardial infarction

Diabetes increases mortality and accelerates left ventricular (LV) dysfunction following myocardial infarction (MI). This study sought to determine the impact of impaired myocardial insulin signaling, in the absence of diabetes, on the development of LV dysfunction following MI. Mice with cardiomyocyte-restricted knock out of the insulin receptor (CIRKO) and wildtype (WT) mice were subjected to proximal left coronary artery ligation (MI) and followed for 14 days. Despite equivalent infarct size, mortality was increased in CIRKO-MI vs. WT-MI mice (68% vs. 40%, respectively). In surviving mice, LV ejection fraction and dP/dt were reduced by >40% in CIRKO-MI vs. WT-MI. Relative to shams, isometric developed tension in LV papillary muscles increased in WT-MI but not in CIRKO-MI. Time to peak tension and relaxation times were prolonged in CIRKO-MI vs. WT-MI suggesting impaired, load-independent myocardial contractile function. To elucidate mechanisms for impaired LV contractility, mitochondrial function was examined in permeabilized cardiac fibers. Whereas maximal ADP-stimulated mitochondrial O(2) consumption rates (V(ADP)) with palmitoyl carnitine were unchanged in WT-MI mice relative to sham-operated animals, V(ADP) was significantly reduced in CIRKO-MI (13.17+/-0.94 vs. 9.14+/-0.88 nmol O(2)/min/mgdw, p<0.05). Relative to WT-MI, expression levels of GLUT4, PPAR-alpha, SERCA2, and the FA-Oxidation genes MCAD, LCAD, CPT2 and the electron transfer flavoprotein ETFDH were repressed in CIRKO-MI. Thus reduced insulin action in cardiac myocytes accelerates post-MI LV dysfunction, due in part to a rapid decline in mitochondrial FA oxidative capacity, which combined with limited glucose transport capacity that may reduce substrate utilization and availability.

Comparison of the Accuracy of Multidetector Computed Tomography Versus Two-Dimensional Echocardiography to Measure Left Atrial Volume

Left atrial (LA) volume is an important prognostic factor in cardiovascular disease. Multidetector computed tomography (MDCT) is an emerging cardiac imaging modality; however, its accuracy in measuring the LA volume has not been well studied. The aim of our study was to determine the accuracy of MDCT in quantifying the LA volume. A total of 48 patients underwent MDCT and 2-dimensional (2D) echocardiography (2DE) on the same day. The area-length and Simpsons methods were used to obtain the 2D echocardiographic LA volume. The LA volume assessment by MDCT was obtained using the modified Simpsons method. Four artificial phantoms were created, and their true volume was assessed by an independent observer using both imaging modalities. The correlation between the LA volume by MDCT and 2DE was significant (r = 0.68). The mean 2D echocardiographic LA volume was lower than the LA volume obtained with MDCT (2DE 79 +/- 37 vs MDCT 103 +/- 32, p <0.05). In the phantom experiment, the volume obtained using MDCT and 2DE correlated significantly with the true volume (r = 0.97, p <0.05 vs r = 0.96, p <0.05, respectively). However, the mean 2D echocardiographic phantom volume was 16% lower than the true volume (2DE, Simpsons method 53 +/- 24 vs the true volume 61 +/- 24, p <0.05). The mean volume calculated using MDCT did not differ from the true volume (MDCT 60 +/- 21 vs true volume 61 +/- 24, p = NS). 2DE appeared to systematically underestimate the LA volume compared to phantom and cardiac MDCT, suggesting that different normal cutoff values should be used for each modality. In conclusion, LA volume quantification using MDCT is an accurate and feasible method.

PKC translocation and ERK1/2 activation in compensated right ventricular hypertrophy secondary to chronic emphysema.

BackgroundRight ventricular hypertrophy (RVH) is an important complication of chronic lung disease. However, the signal transduction pathways involved as well as the physiological changes to the right ventricle have not been investigated. Emphysema was produced in male, Syrian Golden hamsters by intra-tracheal instillation of 250 IU/kg elastase (Emp, n = 17). Saline treated animals served as controls (Con, n = 15).ResultsNine months later, Emp hamsters had 75% greater lung volume, and evidence of RVH at the gross and myocyte level (RV:tibia length Emp 6.84 ± 1.18 vs. Con 5.14 ± 1.11 mg/mm; myocyte cross sectional area Emp 3737 vs. Con 2695 μm2), but not left ventricular hypertrophy. Serial echocardiographic analysis from baseline to nine months after induction of emphysema revealed increasing right ventricular internal dimension and decreased pulmonary artery acceleration time only in Emp hamsters. There was an increase in translocation of PKC βI and PKC ε from cytosolic to membranous cell fractions in RV of Emp hamsters. Phosphorylation of PKC ε was unchanged. Translocation of PKC α and βII were unchanged. Emp animals had a 22% increase in phospho-ERK 1/2, but no change in levels of total ERK 1/2 compared to Con.ConclusionThese data suggest that PKC βI, ε and ERK 1/2 may play a role in mediating compensated RVH secondary to emphysema and may have clinical relevance in the pathogenesis of RVH.

Response to a Possible Role of Visceral Fat-Related Inflammation in Linking Obstructive Sleep Apnea to Left Ventricular Hypertrophy

We thank Drs Cereda and Malavazos1 for their comments regarding our article “Left Ventricular Hypertrophy in Severe Obesity. Interactions Among Blood Pressure, Nocturnal Hypoxemia, and Body Mass.”2 They point out a potential role for inflammation mediated by visceral adipose tissue as a contributing factor for the cardiac abnormalities that we observed in …

The Influence of Multiple Variables on the Prevalence of Aspirin Prescribing in Patients with Known Coronary Artery Disease

Background and Objective: To determine the prevalence of aspirin prescribing in patients with known coronary artery disease (CAD) at admission and discharge as well as the changes in the prevalence, both as a function of the patients’ status and the specialty of the treating physician. Methods: This was a retrospective chart review. Patients admitted with a diagnosis of CAD during a 1-year period were studied. Data were collected on aspirin prescribing prior to admission, aspirin prescribed at discharge, age, gender, insurance status, physician type, smoking, hypercholesterolemia, hypertension and diabetes. Results: 1,061 charts were reviewed. After adjustment, there was a significantly higher rate of aspirin prescribing prior to admission for male patients [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.01–1.75] and patients with hypercholesterolemia (OR 1.37, 95% CI 1.05–1.78). At hospital discharge, there was no significant difference with respect to any of the eight variables of interest. For all patients, the prescribing of aspirin was significantly higher at discharge than prior to hospital admission (85 vs. 69%, p < 0.05). Conclusion: In the present sample, aspirin use in patients with known CAD was higher at hospital discharge. Our results indicate an improvement in the care of patients with known CAD, but this is still suboptimal considering the evidence of benefit.

Effect of Adjuvant Chemotherapy on Left Ventricular Remodeling in Women with Newly Diagnosed Primary Breast Cancer: A Pilot Prospective Longitudinal Cardiac Magnetic Resonance Imaging Study

Purpose: The aim of this study was to assess the left ventricular (LV) remodeling response to chemotherapy in low–cardiac-risk women with newly diagnosed nonmetastatic breast cancer. Cardiotoxic effects of chemotherapy are an increasing concern. To effectively interpret cardiac imaging studies performed for screening purposes in patients undergoing cancer therapy it is necessary to understand the normal changes in structure and function that may occur. Methods: Twenty women without preexisting cardiovascular disease, of a mean age of 50 years, newly diagnosed with nonmetastatic breast cancer and treated with anthracycline or trastuzumab, were prospectively enrolled and evaluated at four time points (at baseline, during chemotherapy, 2 weeks after chemotherapy, and 6 months after chemotherapy) using cardiac magnetic resonance imaging, blood samples, and a clinical questionnaire. Results: Over a 6-month period, the left ventricular ejection fraction (%) decreased (64.15±5.30 to 60.41±5.77, P<0.002) and the LV end-diastolic (mm) and end-systolic (mm) volumes increased (124.73±20.25 to 132.21±19.33, P<0.04 and 45.16±11.88 to 52.57±11.65, P<0.00, respectively). The LV mass (g) did not change (73.06±11.51 to 69.21±15.3, P=0.08), but the LV mass to LVEDV ratio (g/mm) decreased (0.594±0.098 to 0.530±0.124, P<0.04). Conclusions: In low–cardiac-risk women with nonmetastatic breast cancer, the increased LV volume and a mildly decreased left ventricular ejection fraction during and after chemotherapy do not seem to be associated with laboratory or clinical evidence of increased risk for heart failure.

Cleft mitral valve appearance on cardiac computed tomography.

f A m Conflict of interest: The authors report no conflicts of interest. * Corresponding author. E-mail address: SAbbara@Partners.org igure 1 A short axis echo and CT images of the cleft mitral va evel of the mitral valve shows a cleft within anterior mitral valve arly diastolic short axis multiplanar reformation in the mitral val hich extends into the mitral annulus. Please note the differences in s well as superior special resolution of CT.