Effectiveness of Systematic Echocardiographic Screening for Rheumatic Heart Disease in Nepalese Schoolchildren: A Cluster Randomized Clinical Trial.

Importance: Echocardiographic screening allows for early detection of subclinical stages of rheumatic heart disease among children in endemic regions. Objective: To investigate the effectiveness of systematic echocardiographic screening in combination with secondary antibiotic prophylaxis on the prevalence of rheumatic heart disease. Design, Setting, and Participants: This cluster randomized clinical trial included students 9 to 16 years of age attending public and private schools in urban and rural areas of the Sunsari district in Nepal that had been randomly selected on November 17, 2012. Echocardiographic follow-up was performed between January 7, 2016, and January 3, 2019. Interventions: In the experimental group, children underwent systematic echocardiographic screening followed by secondary antibiotic prophylaxis in case they had echocardiographic evidence of latent rheumatic heart disease. In the control group, children underwent no echocardiographic screening. Main Outcomes and Measures: Prevalence of the composite of definite or borderline rheumatic heart disease according to the World Heart Federation criteria in experimental and control schools as assessed 4 years after intervention. Results: A total of 35 schools were randomized to the experimental group (n = 19) or the control group (n = 16). After a median of 4.3 years (interquartile range [IQR], 4.0-4.5 years), 17 of 19 schools in the experimental group (2648 children; median age at follow-up, 12.1 years; IQR, 10.3-12.5 years; 1308 [49.4%] male) and 15 of 16 schools in the control group (1325 children; median age at follow-up, 10.6 years; IQR, 10.0-12.5 years; 682 [51.5%] male) underwent echocardiographic follow-up. The prevalence of definite or borderline rheumatic heart disease was 10.8 per 1000 children (95% CI, 4.7-24.7) in the control group and 3.8 per 1000 children (95% CI, 1.5-9.8) in the experimental group (odds ratio, 0.34; 95% CI, 0.11-1.07; P = .06). The prevalence in the experimental group at baseline had been 12.9 per 1000 children (95% CI, 9.2-18.1). In the experimental group, the odds ratio of definite or borderline rheumatic heart disease at follow-up vs baseline was 0.29 (95% CI, 0.13-0.65; P = .008). Conclusions and Relevance: School-based echocardiographic screening in combination with secondary antibiotic prophylaxis in children with evidence of latent rheumatic heart disease may be an effective strategy to reduce the prevalence of definite or borderline rheumatic heart disease in endemic regions. Trial Registration: ClinicalTrials.gov Identifier: NCT01550068.

Development of a risk score for early saphenous vein graft failure: An individual patient data meta-analysis.

OBJECTIVES: Early saphenous vein graft (SVG) occlusion is typically attributed to technical factors. We aimed at exploring clinical, anatomical, and operative factors associated with the risk of early SVG occlusion (within 12 months postsurgery). METHODS: Published literature in MEDLINE was searched for studies reporting the incidence of early SVG occlusion. Individual patient data (IPD) on early SVG occlusion were used from the SAFINOUS-CABG Consortium. A derivation (n = 1492 patients) and validation (n = 372 patients) cohort were used for model training (with 10-fold cross-validation) and external validation respectively. RESULTS: In aggregate data meta-analysis (48 studies, 41,530 SVGs) the pooled estimate for early SVG occlusion was 11%. The developed IPD model for early SVG occlusion, which included clinical, anatomical, and operative characteristics (age, sex, dyslipidemia, diabetes mellitus, smoking, serum creatinine, endoscopic vein harvesting, use of complex grafts, grafted target vessel, and number of SVGs), had good performance in the derivation (c-index = 0.744; 95% confidence interval [CI], 0.701-0.774) and validation cohort (c-index = 0.734; 95% CI, 0.659-0.809). Based on this model. we constructed a simplified 12-variable risk score system (SAFINOUS score) with good performance for early SVG occlusion (c-index = 0.700, 95% CI, 0.684-0.716). CONCLUSIONS: From a large international IPD collaboration, we developed a novel risk score to assess the individualized risk for early SVG occlusion. The SAFINOUS risk score could be used to identify patients that are more likely to benefit from aggressive treatment strategies.

Prognostic Value of Early Postoperative Troponin T in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Cardiac troponin T (cTnT) is elevated after coronary artery bypass grafting surgery. The aim of this study was to determine the association between cTnT elevations between 6 and 12 hours after coronary artery bypass grafting and in-hospital outcome. METHODS AND RESULTS: We prospectively studied 1722 patients undergoing isolated coronary artery bypass grafting. We assessed the association between conventional cTnT (749 patients) and high-sensitivity cTnT (hs-cTnT; 973 patients) 6 to 12 hours postoperatively with in-hospital major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, or stroke. The prespecified secondary outcome was a safety composite of MACCE, resuscitation, intensive care unit readmission or admission ≥48 hours, inotrope or vasopressor use ≥24 hours, or new-onset renal insufficiency. Among patients with a conventional cTnT measurement, 92 experienced a MACCE (12%) and 146 experienced a safety composite event (19%). Likewise, for hs-cTnT, 114 experienced a MACCE (12%) and 153 experienced a safety composite event (16%). Compared with cTnT ≤200 ng/L, each 200-ng/L increment in cTnT was associated with a monotonous increase in the odds of MACCE and the safety composite outcome. Conventional and hs-cTnT demonstrated moderate discrimination for MACCE (areas under the fitted receiver operating characteristics curve, 0.72 and 0.77 for conventional and hs-cTnT, respectively) and the safety composite outcome (areas under the fitted receiver operating characteristics curve, 0.66 and 0.74 for conventional and hs-cTnT, respectively) and resulted in improved prognostic performance when added to the EuroSCORE. At a cutoff of 800 ng/L, conventional and hs-cTnT provided clinically relevant power to rule in MACCE and the safety composite outcome. CONCLUSIONS: cTnT levels assessed between 6 and 12 hours after coronary artery bypass grafting identify patients at increased risk of MACCE or other complications.

Income Disparities in Absolute Cardiovascular Risk and Cardiovascular Risk Factors in the United States, 1999-2014.

Importance: Large improvements in the control of risk factors for cardiovascular disease have been achieved in the United States, but it remains unclear whether adults in all socioeconomic strata have benefited equally. Objective: To assess temporal trends in 10-year predicted absolute cardiovascular risk and cardiovascular risk factors among US adults in different socioeconomic strata. Design, Setting, and Participants: A cross-sectional analysis was conducted using data on adults 40 to 79 years of age without established cardiovascular disease from the 1999 to 2014 National Health and Nutrition Examination Survey. Exposures: Socioeconomic status was based on the family income to poverty ratio and participants were divided into the following 3 groups: high income (family income to poverty ratio, ≥4), middle income (>1 and <4), or at or below the federal poverty level (≤1). Main Outcomes and Measures: We assessed predicted absolute cardiovascular risk using the pooled cohort equation. We assessed the following 4 risk factors: systolic blood pressure, smoking status, diabetes, and total cholesterol. Results: Of the 17 199 adults whose data were included in the study (8828 women and 8371 men; mean age, 54.4 years), from 1999-2014, trends in the percentage of adults with predicted absolute cardiovascular risk of 20% or more, mean systolic blood pressure, and the percentage of current smokers varied by income strata (P ≤ .02 for interaction). For adults with incomes at or below the federal poverty level, there was little evidence of a change in any of these outcomes across survey years (cardiovascular risk ≥20%, 14.9% [95% CI, 12.9%-16.8%] in 1999-2004; 16.5% [95% CI, 13.7%-19.2%] in 2011-2014; P = .41; mean systolic blood pressure, 127.6 [95% CI, 126.1-129.0] mm Hg in 1999-2004; 126.8 [95% CI, 125.2-128.5] mm Hg in 2011-2014; P = .44; and smoking, 36.5% [95% CI, 32.1%-41.0%] in 1999-2004; 36.0% [95% CI, 31.1%-40.8%] in 2011-2014; P = .87). For adults in the high-income stratum, these variables decreased across survey years (cardiovascular risk ≥20%, 12.0% [95% CI, 10.7%-13.3%] in 1999-2004; 9.5% [95% CI, 8.2%-10.7%] in 2011-2014; P = .003; systolic blood pressure, 126.0 [95% CI, 125.0-126.9] mm Hg in 1999-2004; 122.3 [95% CI, 121.3-123.3] mm Hg in 2011-2014; P < .001; and smoking, 14.1% [95% CI, 12.0%-16.2%] in 1999-2004; 8.8% [95% CI, 6.6%-11.0%] in 2011-2014; P = .001). Trends in the percentage of adults with diabetes and the mean total cholesterol level did not vary by income. Conclusions and Relevance: Adults in each socioeconomic stratum have not benefited equally from efforts to control cardiovascular risk factors.

A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. Acthar® Gel) in nephrotic syndrome due to idiopathic membranous nephropathy.

BACKGROUND: H.P. Acthar(®) Gel is currently the only Food and Drug Administration therapy approved for the treatment of nephrotic syndrome. Active drug ingredients include structurally related melanocortin peptides that bind to cell surface G-protein-coupled receptors known as melanocortin receptors, which are expressed in glomerular podocytes. In animal models of membranous nephropathy, stimulation has been demonstrated to reduce podocyte injury and loss. We hypothesized that H.P. Acthar(®) Gel would improve symptoms of the nephrotic syndrome in patients with idiopathic membranous nephropathy. METHODS: Twenty patients received a subcutaneous dose of 40 or 80 IU twice weekly. Changes in proteinuria, albumin, cholesterol profile, estimated glomerular filtration rate and serum anti-PLA2R antibodies were assessed at baseline and in response to treatment along with tolerance and safety. RESULTS: Baseline characteristics included mean proteinuria (9.1 ± 3.4 g/day), albumin (2.7 ± 0.8 g/dL), estimated glomerular filtration rate (77 ± 30 mL/min) along with elevated total and low-density lipoprotein (LDL) cholesterol. By 12 months of follow-up, there was a significant improvement in proteinuria in the entire cohort, decreasing to 3.87 ± 4.24 g/day (P < 0.001) with significant improvements in serum albumin, total and LDL cholesterol. A >50% decrease in proteinuria was noted in 65% of the patients with a trend toward better outcomes among patients who received greater cumulative doses. No significant adverse effects were documented. Clearing of serum anti-PLA2R antibodies prior to or in parallel with proteinuria improvement was noted in some, but not all patients. CONCLUSIONS: H.P. Acthar(®) Gel is a potential therapy for nephrotic syndrome secondary to idiopathic membranous nephropathy that deserves further study.

Cystatin C and acute changes in glomerular filtration rate.

The identification of an effective marker of acutely changing kidney function is a priority in clinical nephrology. While serum creatinine is the most widely used surrogate for glomerular filtration rate (GFR), its vulnerability to non-glomerular clearance results in biased estimates of GFR and may delay the identification of acute changes. Alternatively, cystatin C (CysC) has been recognized as a promising marker of GFR. Controlled physiological studies in diabetes, protein-induced glomerular hyperfiltration and extreme exercise demonstrated that acute changes in CysC provide a better approximation of GFR than serum creatinine. Clinical studies examining contrast induced nephropathy, acute kidney injury, and kidney transplantation have also demonstrated several possible advantages of CysC with respect to accurately measuring GFR and early diagnosis of renal dysfunction. CysC measurements also provide ancillary benefits such as improved prediction of patient outcomes and prognosis. Our aim was to review the literature on short-term changes in CysC over days, weeks and months to explore the clinical utility of CysC in the acute setting. Based on existing evidence, CysC may improve clinicians' ability to detect acute changes in kidney function.

The kidney in normal pregnancy and preeclampsia.

Complicating up to 8% of pregnancies, preeclampsia is, in fact, the most common glomerular disease worldwide. In this article, we review the effect of normal pregnancy on the kidney as well as the role of the kidney in preeclampsia. We discuss blood pressure in pregnancy and preeclampsia, followed by the physiology of hyperfiltration in normal pregnancy as well as the pathophysiology of hypofiltration and proteinuria in preeclampsia. Recent studies have suggested that the clinical syndrome of preeclampsia, which recovers rapidly after delivery of the placenta, is caused by impaired vascular endothelial growth factor signaling that disturbs the status of vascular dilatation as well as the symbiosis between the glomerular endothelium and the podocytes. Finally, we discuss the intriguing association between chronic kidney disease (CKD) and preeclampsia. We hypothesize that the imbalance between angiogenic and anti-angiogenic factors, which may be common to both preeclampsia and CKD, might explain why CKD predisposes pregnant women to develop preeclampsia.