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

Atherosclerosis of the ascending aorta is an independent predictor of long-term neurologic events and mortality

AbstractOBJECTIVESThis study was undertaken to determine whether atherosclerosis of the ascending aorta is a predictor of long-term neurologic events and mortality.BACKGROUNDAtherosclerosis of the thoracic aorta has been recently considered a significant predictor of neurologic events and peripheral embolism, but not of long-term mortality.METHODSLong-term follow-up (a total of 5,859 person-years) was conducted of 1,957 consecutive patients ≥50 years old who underwent cardiac surgery. Atherosclerosis of the ascending aorta was assessed intraoperatively (epiaortic ultrasound) and patients were divided into four groups according to severity (normal, mild, moderate or severe). Carotid artery disease was evaluated (carotid ultrasound) in 1,467 (75%) patients. Cox proportional-hazards regression analysis was performed to assess the independent effect of predictors on neurologic events and mortality.RESULTSA total of 491 events occurred in 472 patients (neurologic events 92, all-cause mortality 399). Independent predictors of long-term neurologic events were: hypertension (p = 0.009), ascending aorta atherosclerosis (p = 0.011) and diabetes mellitus (p = 0.015). The independent predictors of mortality were advanced age (p < 0.0001), left ventricular dysfunction (p < 0.0001), ascending aorta atherosclerosis (p < 0.0001), hypertension (p = 0.0001) and diabetes mellitus (p = 0.0002). There was >1.5-fold increase in the incidence of both neurologic events and mortality as the severity of atherosclerosis increased from normal-mild to moderate, and a greater than threefold increase in the incidence of both as the severity of atherosclerosis increased from normal-mild to severe.CONCLUSIONSAtherosclerosis of the ascending aorta is an independent predictor of long-term neurologic events and mortality. These results provide additional evidence that in addition to being a direct cause of cerebral atheroembolism, an atherosclerotic ascending aorta may be a marker of generalized atherosclerosis and thus of increased morbidity and mortality

Disseminating and implementing a lifestyle-based healthy weight program for mothers in a national organization: A study protocol for a cluster randomized trial

BACKGROUND: Excessive weight gain among young adult women age 18-45 years is an alarming and overlooked trend that must be addressed to reverse the epidemics of obesity and chronic disease. During this vulnerable period, women tend to gain disproportionally large amounts of weight compared to men and to other life periods. Healthy Eating and Active Living Taught at Home (HEALTH) is a lifestyle modification intervention developed in partnership with Parents as Teachers (PAT), a national home visiting, community-based organization with significant reach in this population. HEALTH prevented weight gain, promoted sustained weight loss, and reduced waist circumference. PAT provides parent-child education and services free of charge to nearly 170,000 families through up to 25 free home visits per year until the child enters kindergarten. METHODS: This study extends effectiveness findings with a pragmatic cluster randomized controlled trial to evaluate dissemination and implementation (D&I) of HEALTH across three levels (mother, parent educator, PAT site). The trial will evaluate the effect of HEALTH and the HEALTH training curriculum (implementation strategy) on weight among mothers with overweight and obesity across the USA (N = 252 HEALTH; N = 252 usual care). Parent educators from 28 existing PAT sites (14 HEALTH, 14 usual care) will receive the HEALTH training curriculum through PAT National Center, using PAT\u27s existing training infrastructure, as a continuing education opportunity. An extensive evaluation, guided by RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance), will determine implementation outcomes (acceptability, adoption, appropriateness, feasibility, fidelity, and adaptation) at the parent educator level. The Conceptual Framework for Implementation Research will characterize determinants that influence HEALTH D&I at three levels: mother, parent educator, and PAT site to enhance external validity (reach and maintenance). DISCUSSION: Embedding intervention content within existing delivery channels can help expand the reach of evidence-based interventions. Interventions, which have been adapted, can still be effective even if the effect is reduced and can still achieve population impact by reaching a broader set of the population. The current study will build on this to test not only the effectiveness of HEALTH in real-world PAT implementation nationwide, but also elements critical to D&I, implementation outcomes, and the context for implementation. TRIAL REGISTRATION: https://ClinicalTrials.gov , NCT03758638 . Registered 29 November 2018

Impact of Gender on the Myocardial Metabolic Response to Obesity

ObjectivesWe sought to determine the gender-specific effects of obesity on myocardial metabolism, work, and efficiency.BackgroundMyocardial metabolism abnormalities may contribute to the development of obesity-related heart failure. Increased myocardial oxygen consumption (MVO2) and fatty acid (FA) metabolism and decreased efficiency occur with obesity in women. It is unknown whether similar changes occur with obesity in men.MethodsWe quantified cardiac work, efficiency, myocardial blood flow (MBF), MVO2, glucose, and FA metabolism with echocardiography and positron emission tomography in nonobese and obese men and women (N = 86).ResultsThere were significant differences between the obese (n = 35) and nonobese (n = 51) subjects in age, body composition, plasma lipids, and insulin resistance in addition to differences between the men (n = 30) and women (n = 56) in body composition and plasma lipids. Female gender independently predicted increased cardiac work (p < 0.001). Female gender also related to lower efficiency (p < 0.05). Obesity and female gender independently predicted greater MBF (p < 0.01, p < 0.0005, respectively) and MVO2 (p < 0.0005, p < 0.0001). Myocardial glucose uptake was not different among the 4 subject groups, but obesity and gender interacted in predicting glucose uptake (p < 0.05). Lower myocardial glucose utilization was independently predicted by female gender (p < 0.05), and it independently predicted lower myocardial glucose utilization/plasma insulin (p < 0.05). Obesity and gender significantly interacted in the determination of glucose utilization/plasma insulin (p = 0.01). There were no differences in FA uptake among the 4 groups, and although increasing obesity correlated with greater myocardial FA utilization and oxidation; female gender (p < 0.005, p < 0.01) and plasma triglycerides (p < 0.05, p < 0.005) were their independent predictors.ConclusionsWomen's and men's myocardial metabolic responses to obesity are not exactly the same. Obesity and gender modulate MBF and MVO2, are related to myocardial substrate metabolism, and sometimes interact in its prediction. Gender modifies efficiency. Gender-related differences in myocardial metabolism may affect the development of/adaptation to obesity-related cardiac disease

Therapeutic end points for the treatment of atrioventricular node reentrant tachycardia by catheter-guided radiofrequency current

AbstractObjectives. The purpose off this prospective study was to test the hypothesis that the elimination of inducible repetitive atrioventricular (AV) node reentry the persistence of slow AV pathway conduction is a valid end point for radiofrequency catheter ablation procedures in patients with supraventricular tachycardia due to AV node reentry.Background. Although modification of AV node physiology by radiofrequency current can eliminate AV node reentrant tachycardia, therapeutic end points that are definitive of a satisfactory result in patients undergoing modification of the slow AV pathway have not been established. Applications of radiofrequency current at selected sites may eliminate all evidence of slow pathway conduction or sufficiently modify the refractory properties of the slow pathway to preclude sustained arrhythmias. Accordingly, total abolition of dual AV node physiology may not be necessary to prevent arrhythmia recurrence.Methods. Radiofrequency catheter ablation of the slow AV pathway was attempted in 59 patients with typical AV node reentry. Tissue ablation was performed with a continuous wave of 500-kHz radiofrequency current. Twenty-five to 35 W was applied for 60 s at the site selected for destruction.Results. Dual AV node physiology was eliminated completely in 35 patients (59%), persisted without inducible AV node reentry in 13 patients (22%) and persisted with inducible single AV reentrant beats in 11 patients (19%). In patients with persistent dual AV node physiology, the maximal difference between the effective refractory period of the fast and slow pathways was reduced from 104 ± 62 ms before the procedure to 37 ± 37 ms after AV conduction had been modified (p < 0.001). During a mean follow-up interval of 15 months (range 4 to 28), only one patient (2%) had a recurrence of the tachycardia.Conclusions. Resulte demonstrate that when complete elimination of dial AV node physiology is difficult, modification of slow pathway conduction to the extent that repetitive AV node reentry cannot be induced is a definitive end point that portends a good prognosis

Dosing pole recommendations for lymphatic filariasis elimination: A height-weight quantile regression modeling approach

BACKGROUND: The World Health Organization (WHO) currently recommends height or age-based dosing as alternatives to weight-based dosing for mass drug administration lymphatic filariasis (LF) elimination programs. The goals of our study were to compare these alternative dosing strategies to weight-based dosing and to develop and evaluate new height-based dosing pole scenarios. METHODOLOGY/PRINCIPAL FINDINGS: Age, height and weight data were collected from \u3e26,000 individuals in five countries during a cluster randomized LF clinical trial. Weight-based dosing for diethylcarbamazine (DEC; 6 mg/kg) and ivermectin (IVM; 200 ug/kg) with tablet numbers derived from a table of weight intervals was treated as the gold standard for this study. Following WHO recommended age-based dosing of DEC and height-based dosing of IVM would have resulted in 32% and 27% of individuals receiving treatment doses below those recommended by weight-based dosing for DEC and IVM, respectively. Underdosing would have been especially common in adult males, who tend to have the highest LF prevalence in many endemic areas. We used a 3-step modeling approach to develop and evaluate new dosing pole cutoffs. First, we analyzed the clinical trial data using quantile regression to predict weight from height. We then used weight predictions to develop new dosing pole cutoff values. Finally, we compared different dosing pole cutoffs and age and height-based WHO dosing recommendations to weight-based dosing. We considered hundreds of scenarios including country- and sex-specific dosing poles. A simple dosing pole with a 6-tablet maximum for both DEC and IVM reduced the underdosing rate by 30% and 21%, respectively, and was nearly as effective as more complex pole combinations for reducing underdosing. CONCLUSIONS/SIGNIFICANCE: Using a novel modeling approach, we developed a simple dosing pole that would markedly reduce underdosing for DEC and IVM in MDA programs compared to current WHO recommended height or age-based dosing

The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design

BACKGROUND: Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF). METHODS: This clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO DISCUSSION: The iNIX-HF phase II clinical trial will evaluate the effectiveness of inorganic nitrate supplements as a new treatment to ameliorate poor exercise capacity in HFrEF. This study also will provide critical preliminary data for a future \u27pivotal\u27, phase III, multi-center trial of the effectiveness of nitrate supplements not only for improving exercise performance, but also for improving symptoms and decreasing other major cardiovascular endpoints. The potential public health impact of identifying a new, relatively inexpensive, safe, and effective treatment that improves overall exercise performance in patients with HFrEF is significant