Atherosclerosis of the ascending aorta is a predictor of renal dysfunction after cardiac operations

AbstractObjectives: Renal dysfunction occurring after cardiac operations has been attributed to various factors, but the importance of an atherosclerotic thoracic aorta has not been previously evaluated. The purpose of this study was to identify predictors of postoperative renal dysfunction (50% or more increase from preoperative values) and to evaluate the importance of atherosclerosis of the ascending aorta as a predictor of this complication. Methods: Nine hundred seventy-eight consecutive patients, 50 years of age and older with normal preoperative renal function (serum creatinine level of 1.5 mg/dL or less), who were scheduled to undergo cardiac surgery were prospectively evaluated. Atherosclerosis of the ascending aorta was assessed during the operation (with epiaortic ultrasound), and patients were divided into 3 groups according to its severity (normal-to-mild, moderate, and severe). Results: Univariate predictors of renal dysfunction at postoperative day 1 were atherosclerosis of the ascending aorta (P < .045) and postoperative low cardiac output (P = .05); at postoperative day 6 they were atherosclerosis of the ascending aorta (P < .0001), postoperative low cardiac output (P < .0001), advanced age (P = .001), decreased preoperative left ventricular function (P = .01), and female gender (P = .03). Multivariate analysis showed that atherosclerosis of the ascending aorta (odds ratio, 3.06; P = .04) was the only independent predictor of postoperative renal dysfunction at day 1 and that postoperative low cardiac output (odds ratio, 4.83; P < .0001), atherosclerosis of the ascending aorta (odds ratio, 2.13; P = .0006), and preoperative left ventricular dysfunction (odds ratio, 1.48; P = .028) were independent predictors of postoperative renal dysfunction at day 6. Conclusions: An atherosclerotic ascending aorta is an important predictor of postoperative renal dysfunction, possibly because atheroembolism to the kidneys occurs in the perioperative period (ie, during surgical manipulation of an atherosclerotic aorta) or because the diseased aorta may be a marker of widespread atherosclerotic disease that may predispose to perioperative renal dysfunction. (J Thorac Cardiovasc Surg 1999;117:111-6

Sex Affects Myocardial Blood Flow and Fatty Acid Substrate Metabolism in Humans with Nonischemic Heart Failure

In animal models of heart failure (HF), myocardial metabolism shifts from the normal preference for high-energy fatty acid (FA) metabolism towards the more efficient fuel, glucose. However, FA (vs. glucose) metabolism generates more ATP/mole; thus FA metabolism may be especially advantageous in HF. Sex modulates myocardial blood flow (MBF) and substrate metabolism in normal humans. Whether sex affects MBF and metabolism in patients with HF is unknown. We studied 19 well-matched men and women with nonischemic HF with similar ejection fractions (all ≤ 35%). MBF and myocardial substrate metabolism were quantified using positron emission tomography. Women had higher MBF (mL/g/min), FA uptake (mL/g/min), utilization (nmol/g/min) (P<0.005, <0.005, <0.05, respectively) and trended towards higher FA oxidation than men (P=0.09). These findings were independent of age, obesity, and insulin resistance. There were no sex-related differences in fasting myocardial glucose uptake or metabolism. In an exploratory analysis of the longitudinal follow-up of these subjects (mean 7 y), we found that 4 men had a major cardiovascular event, while one woman died of non-cardiac causes. Higher MBF related to improved event-free survival (HR=0.31, P=0.02). In sum, in nonischemic HF, women have higher MBF and FA uptake and metabolism than men, and these changes are not due to differences in other variables that can affect myocardial metabolism (e.g., age, obesity, or insulin resistance). Moreover, higher MBF portends a better prognosis. These sex-related differences should be taken into account in the development and targeting of novel agents aimed at modulating in MBF and metabolism in HF

Ultrasound Core Laboratory for the Household Air Pollution Intervention Network Trial: Standardized Training and Image Management for Field Studies Using Portable Ultrasound in Fetal, Lung, and Vascular Evaluations

Ultrasound Core Laboratories (UCL) are used in multicenter trials to assess imaging biomarkers to define robust phenotypes, to reduce imaging variability and to allow blinded independent review with the purpose of optimizing endpoint measurement precision. The Household Air Pollution Intervention Network, a multicountry randomized controlled trial (Guatemala, Peru, India and Rwanda), evaluates the effects of reducing household air pollution on health outcomes. Field studies using portable ultrasound evaluate fetal, lung and vascular imaging endpoints. The objective of this report is to describe administrative methods and training of a centralized clinical research UCL. A comprehensive administrative protocol and training curriculum included standard operating procedures, didactics, practical scanning and written/practical assessments of general ultrasound principles and specific imaging protocols. After initial online training, 18 sonographers (three or four per country and five from the UCL) participated in a 2 wk on-site training program. Written and practical testing evaluated ultrasound topic knowledge and scanning skills, and surveys evaluated the overall course. The UCL developed comprehensive standard operating procedures for image acquisition with a portable ultrasound system, digital image upload to cloud-based storage, off-line analysis and quality control. Pre- and post-training tests showed significant improvements (fetal ultrasound: 71% ± 13% vs. 93% ± 7%, p < 0.0001; vascular lung ultrasound: 60% ± 8% vs. 84% ± 10%, p < 0.0001). Qualitative and quantitative feedback showed high satisfaction with training (mean, 4.9 ± 0.1; scale: 1 = worst, 5 = best). The UCL oversees all stages: training, standardization, performance monitoring, image quality control and consistency of measurements. Sonographers who failed to meet minimum allowable performance were identified for retraining. In conclusion, a UCL was established to ensure accurate and reproducible ultrasound measurements in clinical research. Standardized operating procedures and training are aimed at reducing variability and enhancing measurement precision from study sites, representing a model for use of portable digital ultrasound for multicenter field studies

Association and interaction of PPAR-complex gene variants with latent traits of left ventricular diastolic function

<p>Abstract</p> <p>Background</p> <p>Abnormalities in myocardial metabolism and/or regulatory genes have been implicated in left ventricular systolic dysfunction. However, the extent to which these modulate left ventricular diastolic function (LVDF) is uncertain.</p> <p>Methods</p> <p>Independent component analysis was applied to extract latent LVDF traits from 14 measured echocardiography-derived endophenotypes of LVDF in 403 Caucasians. Genetic association was assessed between measured and latent LVDF traits and 64 single nucleotide polymorphisms (SNPs) in three peroxisome proliferator-activated receptor <it>(PPAR)</it>-complex genes involved in the transcriptional regulation of fatty acid metabolism.</p> <p>Results</p> <p>By linear regression analysis, 7 SNPs (4 in <it>PPARA</it>, 2 in <it>PPARGC1A</it>, 1 in <it>PPARG</it>) were significantly associated with the latent LVDF trait, whereas a range of 0-4 SNPs were associated with each of the 14 measured echocardiography-derived endophenotypes. Frequency distribution of <it>P </it>values showed a greater proportion of significant associations with the latent LVDF trait than for the measured endophenotypes, suggesting that analyses of the latent trait improved detection of the genetic underpinnings of LVDF. Ridge regression was applied to investigate within-gene and gene-gene interactions. In the within-gene analysis, there were five significant pair-wise interactions in <it>PPARGC1A </it>and none in <it>PPARA </it>or <it>PPARG</it>. In the gene-gene analysis, significant interactions were found between rs4253655 in <it>PPARA </it>and rs1873532 (p = 0.02) and rs7672915 (p = 0.02), both in <it>PPARGC1A</it>, and between rs1151996 in <it>PPARG </it>and rs4697046 in <it>PPARGC1A </it>(p = 0.01).</p> <p>Conclusions</p> <p>Myocardial metabolism <it>PPAR</it>-complex genes, including within and between genes interactions, may play an important role modulating left ventricular diastolic function.</p

Echocardiographic characterization of the improvement in right ventricular function in patients with severe pulmonary hypertension after single-lung transplantation

AbstractObjectives. This study was designed to characterize immediate, early and long-term changes in right ventricular structure and function, as defined by two-dimensional and Doppler echocardiography, after single-lung transplantation in patients with severe pulmonary hypertension.Bacground. Single-lung transplantation has recently been shown to dramatically improve hemodynamics in patients with primary pulmonary hypertension who had unsuccessful medical therapy.Method. Fourteen patients with severe pulmonary hypertension who underwent single-lung transplantation were studied with transthoracic and transesophageal two-dimensional and Doppler echocardiography. Right ventricular dimensions were measured in the apical four-chamber view. Right ventricular ejection and acceleration times and peak velocity of tricuspid regurgitation were measured by Doppler study. Results of right heart catheterization were available early (<3 months) after transplantation in 10 of 13 patients and late after transplantation (6 month to 2 years) in 11 patients.Results. In the early posttransplantation studies, right ventricular dimensions decreased and fractional area change and ejection fraction increased in all patients, but right ventricular wall thickness did not change significantly. Tricuspid regurgitation lessened markedly in all patients. Long-term decreases in right ventricular dimension and improvement in systolic function were sustained. Right ventricular wall thickness significantly decreased compared with the early postoperative value (0.76 ± 0.1 cm compared with 0.63 ± 0.14 cm, p < 0.02).Conclusions. Two-dimensional echocardiography demonstrates sustained improvement in right ventricular function after single-lung transplantation for severe pulmonary hypertension despite severe preoperative dysfunction