The aim of this study was to validate speckle tracking echocardiography (STE) as a method for angle-independent measurement of regional myocardial strain, using sonomicrometry and magnetic resonance ...imaging (MRI) tagging as reference methods.
Tissue Doppler imaging allows non-invasive measurement of myocardial strain in the left ventricle (LV), but is limited by angle dependency.
Strain measurements with STE were obtained by a custom-made program that allowed tracking of two-dimensional motion of speckle patterns in a B-mode image. In anesthetized dogs, we compared LV long- and short-axis measurements by STE to sonomicrometry during preload changes and regional myocardial ischemia. Measurements in the two orthogonal axes were obtained simultaneously in a single imaging plane. In human subjects, long-axis strain by STE and MRI tagging were compared in multiple segments of the LV.
In the experimental study there was good correlation and agreement between STE and sonomicrometry for systolic strain in the long axis (r = 0.90, p < 0.001; 95% limits of agreement -4.4% to 5.0%) and systolic shortening in the short axis (r = 0.79, p < 0.001; -5.6% to 5.1%). In the clinical study, 80% of the segments could be analyzed, and correlation and agreement between STE and MRI tagging were good (r = 0.87, p < 0.001; -9.1% to 8.0%).
Speckle tracking echocardiography provides accurate and angle-independent measurements of LV dimensions and strains and has potential to become a clinical bedside tool for quantifying myocardial strain.
The objectives of this study were to determine the associations of the metabolic syndrome, inflammatory markers, and insulin resistance with incident congestive heart failure (CHF), beyond ...established risk factors, and to examine whether these risk factors may provide the link between obesity and CHF.
Recently, increasing interest has emerged on the potential role of novel risk factors such as systemic inflammation, insulin resistance, and albuminuria in the pathophysiology of CHF and their relationship with obesity.
The MESA (Multi-Ethnic Study of Atherosclerosis) study is a community-based multicenter cohort study of 6,814 participants (age 45 to 84 years, 3,601 women) of 4 ethnicities: Caucasians, African Americans, Hispanics, and Chinese Americans. Participants were recruited between 2000 and 2002 from 6 U.S. communities. Median follow-up time was 4 years. Participants with history of symptomatic cardiovascular disease were excluded. Cox proportional hazards models were used to analyze the associations of the metabolic syndrome, inflammatory markers, insulin resistance, and albuminuria with incident CHF, independent of established risk factors (age, gender, hypertension, diabetes mellitus, left ventricular hypertrophy, obesity, serum total cholesterol, and smoking), an interim myocardial infarction, and baseline magnetic resonance imaging parameters of left ventricular structure and function.
A total of 79 participants developed CHF during follow-up, and 26 participants (32.9%) had a myocardial infarction prior to CHF and 65% of the cases had CHF with preserved function (left ventricular ejection fraction >or=40%). In multivariable analyses, serum interleukin-6 (hazard ratio HR for 1 standard deviation 1.50, 95% confidence interval CI 1.10 to 2.03) or C-reactive protein (HR for 1 standard deviation 1.38; 95% CI 1.01 to 1.86) and macroalbuminuria (HR 4.31, 95% CI 1.58 to 11.76) were predictors of CHF, independent of obesity and the other established risk factors. Although obesity was significantly associated with incident CHF, this association was no longer significant after adding inflammatory markers (interleukin-6 or C-reactive protein) to the model.
Inflammatory markers and albuminuria are independent predictors of CHF. The association of obesity and CHF may be related to pathophysiologic pathways associated with inflammation.
To evaluate the relationships of right ventricular (RV) and left ventricular (LV) myocardial perfusion reserves with ventricular function and pulmonary hemodynamics in patients with pulmonary ...arterial hypertension (PAH) by using adenosine stress perfusion cardiac magnetic resonance (MR) imaging.
This HIPAA-compliant study was institutional review board approved. Twenty-five patients known or suspected to have PAH underwent right heart catheterization and adenosine stress MR imaging on the same day. Sixteen matched healthy control subjects underwent cardiac MR imaging only. RV and LV perfusion values at rest and at adenosine-induced stress were calculated by using the Fermi function model. The MR imaging-derived RV and LV functional data were calculated by using dedicated software. Statistical testing included Kruskal-Wallis tests for continuous data, Spearman rank correlation tests, and multiple linear regression analyses.
Seventeen of the 25 patients had PAH: 11 with scleroderma-associated PAH, and six with idiopathic PAH. The remaining eight patients had scleroderma without PAH. The myocardial perfusion reserve indexes (MPRIs) in the PAH group (median RV MPRI, 1.7 25th-75th percentile range, 1.3-2.0; median LV MPRI, 1.8 25th-75th percentile range, 1.6-2.1) were significantly lower than those in the scleroderma non-PAH (median RV MPRI, 2.5 25th-75th percentile range, 1.8-3.9 P = .03; median LV MPRI, 4.1 25th-75th percentile range, 2.6-4.8 P = .0003) and control (median RV MPRI, 2.9 25th-75th percentile range, 2.6-3.6 P < .01; median LV MPRI, 3.6 25th-75th percentile range, 2.7-4.1 P < .01) groups. There were significant correlations between biventricular MPRI and both mean pulmonary arterial pressure (mPAP) (RV MPRI: ρ = -0.59, Bonferroni P = .036; LV MPRI: ρ = -0.79, Bonferroni P < .002) and RV stroke work index (RV MPRI: ρ = -0.63, Bonferroni P = .01; LV MPRI: ρ = -0.75, Bonferroni P < .002). In linear regression analysis, mPAP and RV ejection fraction were independent predictors of RV MPRI. mPAP was an independent predictor of LV MPRI.
Biventricular vasoreactivity is significantly reduced with PAH and inversely correlated with RV workload and ejection fraction, suggesting that reduced myocardial perfusion reserve may contribute to RV dysfunction in patients with PAH.
To compare the diagnostic performance of myocardial computed tomographic (CT) perfusion imaging and single photon emission computed tomography (SPECT) perfusion imaging in the diagnosis of ...anatomically significant coronary artery disease (CAD) as depicted at invasive coronary angiography.
This study was approved by the institutional review board. Written informed consent was obtained from all patients. Sixteen centers enrolled 381 patients from November 2009 to July 2011. Patients underwent rest and adenosine stress CT perfusion imaging and rest and either exercise or pharmacologic stress SPECT before and within 60 days of coronary angiography. Images from CT perfusion imaging, SPECT, and coronary angiography were interpreted at blinded, independent core laboratories. The primary diagnostic parameter was the area under the receiver operating characteristic curve (Az). Sensitivity and specificity were calculated with use of prespecified cutoffs. The reference standard was a stenosis of at least 50% at coronary angiography as determined with quantitative methods.
CAD was diagnosed in 229 of the 381 patients (60%). The per-patient sensitivity and specificity for the diagnosis of CAD (stenosis ≥50%) were 88% (202 of 229 patients) and 55% (83 of 152 patients), respectively, for CT perfusion imaging and 62% (143 of 229 patients) and 67% (102 of 152 patients) for SPECT, with Az values of 0.78 (95% confidence interval: 0.74, 0.82) and 0.69 (95% confidence interval: 0.64, 0.74) (P = .001). The sensitivity of CT perfusion imaging for single- and multivessel CAD was higher than that of SPECT, with sensitivities for left main, three-vessel, two-vessel, and one-vessel disease of 92%, 92%, 89%, and 83%, respectively, for CT perfusion imaging and 75%, 79%, 68%, and 41%, respectively, for SPECT.
The overall performance of myocardial CT perfusion imaging in the diagnosis of anatomic CAD (stenosis ≥50%), as demonstrated with the Az, was higher than that of SPECT and was driven in part by the higher sensitivity for left main and multivessel disease.
Weight regain frequently follows interventions that reduce body weight, leading to a failure in long-term obesity treatment. Inhibitory proteins of the leptin signaling pathway, such as the ...suppressor of cytokine signaling 3 (SOCS3), have been studied in conditions that predispose animals to obesity. However, whether SOCS3 modulates postrestriction hyperphagia and weight regain remains unknown. Mice lacking SOCS3 protein specifically in leptin receptor (LepR)-expressing cells (LepR SOCS3 knockout KO) were generated and studied in fasting and refeeding conditions. LepR SOCS3 KO mice exhibited increased leptin sensitivity in the hypothalamus. Notably, LepR SOCS3 KO males and females showed attenuated food intake and weight regain after 48 hours of fasting. Postrestriction hyperleptinemia was also prevented in LepR SOCS3 KO mice. Next, we studied possible mechanisms and neural circuits involved in the SOCS3 effects. SOCS3 deletion did not prevent fasting- or refeeding-induced c-Fos expression in the arcuate nucleus of the hypothalamus (ARH) nor fasting-induced increased excitability of ARH LepR-expressing cells. On the other hand, SOCS3 ablation reduced the mRNA levels of hypothalamic orexigenic neuropeptides during fasting (neuropeptide Y, agouti-related protein, orexin, and melanin-concentrating hormone). In summary, our findings suggest that increased leptin sensitivity contributes to the maintenance of a reduced body weight after food deprivation. In addition, the attenuated postrestriction food intake observed in mutant mice was not explained by fasting-induced changes in the activity of ARH neurons but exclusively by a lower transcription of orexigenic neuropeptides during fasting. These results indicate a partial dissociation between the regulation of neuronal activity and gene expression in ARH LepR-expressing cells.
The classic cardiovascular complication of chronic obstructive pulmonary disease (COPD) is cor pulmonale or right ventricular (RV) enlargement. Most studies of cor pulmonale were conducted decades ...ago.
This study sought to examine RV changes in contemporary COPD and emphysema using cardiac magnetic resonance (CMR) imaging.
We performed a case-control study nested predominantly in 2 general population studies of 310 participants with COPD and control subjects 50 to 79 years of age with ≥10 pack-years of smoking who were free of clinical cardiovascular disease. RV volumes and mass were assessed using magnetic resonance imaging. COPD and COPD severity were defined according to standard spirometric criteria. The percentage of emphysema was defined as the percentage of lung regions <-950 Hounsfield units on full-lung computed tomography; emphysema subtypes were scored by radiologists. Results were adjusted for age, race/ethnicity, sex, height, weight, smoking status, pack-years, systemic hypertension, and sleep apnea.
Right ventricular end-diastolic volume (RVEDV) was reduced in COPD compared with control subjects (-7.8 ml; 95% confidence interval: -15.0 to -0.5 ml; p = 0.04). Increasing severity of COPD was associated with lower RVEDV (p = 0.004) and lower RV stroke volume (p < 0.001). RV mass and ejection fraction were similar between the groups. A greater percentage of emphysema also was associated with lower RVEDV (p = 0.005) and stroke volume (p < 0.001), as was the presence of centrilobular and paraseptal emphysema.
RV volumes are lower without significant alterations in RV mass and ejection fraction in contemporary COPD, and this reduction is related to the greater percentage of emphysema on computed tomography.
Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies.
To test the ability of random survival forests, a machine learning ...technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores.
We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%-25%).
Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.
As a result of warming and precipitation deficits, the increasing shortage of water resources, droughts have become one of the main drivers of desertification, land degradation and food insecurity ...with direct impacts on ecosystems and society, especially in fragile communities. Over the Iberian Peninsula, a known climate change hotspot, the occurrence of droughts varies in intensity and severity, being its assessment under present and future conditions an important tool for adaptation measures. Here, for the first time, we present a comprehensive analysis of different plausible evolutions of droughts throughout the twenty-first century over Iberia on a monthly basis, featuring three different emission scenarios (RCP2.6, RCP4.5, RCP8.5). A multi-variable, multi-model EURO-CORDEX weighted ensemble is used to assess future drought conditions using the SPI (Standardized Precipitation Index) and SPEI (Standardized Precipitation Evapotranspiration Index). All indexes were computed by considering the full period, from 1971 to 2000 merged with 2011–2100 from each RCP scenario. The results clearly show that the Iberian Peninsula is highly vulnerable to climate change, indicating a significant increase in the intensity and severity of drought occurrences, even for the low-end RCP2.6 scenario. For the RCP4.5 and RCP8.5 scenarios, the increases are more pronounced and enhanced throughout the twenty-first century, from 3 up to 12 more severe droughts for the shorter timescales with increases in mean duration above 30 months for the longer accumulation periods. The use of all the RCPs data pooled together with a multi-variable weighted ensemble approach allows not only a more accurate and robust projection of future droughts but also ensures comparability among the projections from the three RCP scenarios. The future drought evolution aspires to assist the new Portuguese national roadmap for adaptation for the twenty-first century, bridging the water sector challenges from mitigation to adaptation in a dynamic way.
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