24-hour ambulatory blood pressure monitoring 9 years after pediatric cardiac surgery: a pilot and feasibility study.

BACKGROUND: Children undergoing cardiac surgery are at risk of high blood pressure (BP), a risk factor for cardiovascular and kidney disease. Twenty-four-hour ambulatory BP monitoring (ABPM) is a reference standard hypertension (HTN) test. Little data exist on ABPM abnormalities in children several years post cardiac surgery. This study aimed to (a) determine ABPM feasibility; (b) describe and compare ABPM measures and abnormalities (percent load, masked HTN [MH]; non-dipping, mean systolic/diastolic BP > 95th percentile; pre-HTN (ABPM); white-coat HTN [WCH]) to casual BP; and (c) compare BP in patients with and without acute kidney injury (AKI). METHODS: Prospective, follow-up pilot study of children (0-18 years) who underwent cardiac surgery from 2007 to 2009 at Montreal Children's Hospital. We recorded if participants had post-operative AKI and assessed the following outcomes at 9-year follow-up: casual BP classified by three single-visit measures (normal; elevated BP [eBPSingleVisit]; HTNSingleVisit); ABPM. Bivariable analyses were used to compare characteristics between groups. RESULTS: Twenty-three patients (median [interquartile range], 8.6 [8.0, 9.0] years post cardiac surgery) were included; 16 (70%) male. Six participants (26%) had eBPSingleVisit or higher. On ABPM, 11 (48%) had ≥ 1 abnormality: 9 (39%) had non-dipping; 3 (13%) had pre-HTN; 3 (13%) had WCH; none had HTN or MH. There were no differences in ABPM according to AKI status. CONCLUSION: Our pilot study determined that ABPM was feasible in children years after cardiac surgery and frequently identified ABPM abnormalities. Future research in larger populations is needed to define specific risk factors for HTN in children after cardiac surgery.

Biomarkers associated with 30-day readmission and mortality after pediatric congenital heart surgery.

OBJECTIVES: Novel cardiac biomarkers serum (suppression of tumorigenicity [ST2]) and Galectin-3 may be associated with an increased likelihood of important events after cardiac surgery. Our objective was to explore the association between pre- and postoperative serum biomarker levels and 30-day readmission or mortality for pediatric patients. METHODS: We prospectively enrolled pediatric patients <18 years of age who underwent at least one cardiac surgical operation at Johns Hopkins Children's Center from 2010 to 2014 (N = 162). Blood samples were collected immediately before surgery and at the end of bypass. We evaluated the association between pre- and postoperative Galectin-3 and ST2 with 30-day readmission or mortality, using backward stepwise logistic regression, adjusting for covariates based on the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Mortality Risk Model. RESULTS: In our cohort, 21 (12.9%) patients experienced readmission or mortality 30-days from discharge. Before adjustment, preoperative ST2 terciles demonstrated a strong association with readmission and/or mortality after surgery (OR: 2.58; 95% CI: 1.17-3.66 and OR: 4.37; 95% CI: 1.31-14.57). After adjustment for covariates based on the STS congenital risk model, Galectin-3 postoperative mid-tercile was significantly associated with 30-day readmission or mortality (OR: 6.17; 95% CI: 1.50-0.43) as was the highest tercile of postoperative ST2 (OR: 4.98; 95% CI: 1.06-23.32). CONCLUSIONS: Elevated pre-and postoperative levels of ST2 and Galectin-3 are associated with increased risk of readmission or mortality after pediatric heart surgery. These clinically available biomarkers can be used for improved risk stratification and may guide improved patient care management.

The Association between Cytokines and 365-Day Readmission or Mortality in Adult Cardiac Surgery.

Cardiac surgery results in a multifactorial systemic inflammatory response with inflammatory cytokines, such as interleukin-10 and 6 (IL-10 and IL-6), shown to have potential in the prediction of adverse outcomes including readmission or mortality. This study sought to measure the association between IL-6 and IL-10 levels and 1-year hospital readmission or mortality following cardiac surgery. Plasma biomarkers IL-6 and IL-10 were measured in 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from eight medical centers participating in the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. Readmission status and mortality were ascertained using Medicare, state all-payer claims, and the National Death Index. We evaluated the association between preoperative and postoperative cytokines and 1-year readmission or mortality using Kaplan-Meier estimates and Cox's proportional hazards modeling, adjusting for covariates used in the Society of Thoracic Surgeons 30-day readmission model. The median follow-up time was 1 year. After adjustment, patients in the highest tertile of postoperative IL-6 values had a significantly increased risk of readmission or death within 1 year (HR: 1.38; 95% CI: 1.03-1.85), and an increased risk of death within 1 year of discharge (HR: 4.88; 95% CI: 1.26-18.85) compared with patients in the lowest tertile. However, postoperative IL-10 levels, although increasing through tertiles, were not found to be significantly associated independently with 1-year readmission or mortality (HR: 1.25; 95% CI: .93-1.69). Pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10 may be postoperative markers of cardiac injury, and IL-6, specifically, shows promise in predicting readmission and mortality following cardiac surgery.

Evaluating biomarkers for prognostic enrichment of clinical trials.

BACKGROUND/AIMS: A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. METHODS: We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. RESULTS: We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. CONCLUSION: In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

Utility of Applying Quality Assessment Tools for Kidneys With KDPI ≥80.

BACKGROUND: Kidneys with "high" Kidney Donor Profile Index (KDPI) are often biopsied and pumped, yet frequently discarded. METHODS: In this multicenter study, we describe the characteristics and outcomes of kidneys with KDPI of 80 or greater that were procured from 338 deceased donors. We excluded donors with anatomical kidney abnormalities. RESULTS: Donors were categorized by the number of kidneys discarded: (1) none (n = 154, 46%), (2) 1 discarded and 1 transplanted (n = 48, 14%), (3) both discarded (n = 136, 40%). Donors in group 3 were older, more often white, and had higher terminal creatinine and KDPI than group 1 (all P < 0.05). Biopsy was performed in 92% of all kidneys, and 47% were pumped. Discard was associated with biopsy findings and first hour renal resistance. Kidney injury biomarker levels (neutrophil gelatinase-associated lipocalin, IL-18, and kidney injury molecule-1 measured from donor urine at procurement and from perfusate soon after pump perfusion) were not different between groups. There was no significant difference in 1-year estimated glomerular filtration rate or graft failure between groups 1 and 2 (41.5 ± 18 vs 41.4 ± 22 mL/min per 1.73 m; P = 0.97 and 9% vs 10%; P = 0.76). CONCLUSIONS: Kidneys with KDPI of 80 or greater comprise the most resource consuming fraction of our donor kidney pool and have the highest rates of discard. Our data suggest that some discarded kidneys with KDPI of 80 or greater are viable; however, current tools and urine and perfusate biomarkers to identify these viable kidneys are not satisfactory. We need better methods to assess viability of kidneys with high KDPI.