NT-proBNP in systemic right ventricles: a new cutoff level for risk stratification?

INTRODUCTION AND OBJECTIVES: The role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the risk prediction of patients with systemic right ventricles (sRV) is not well defined. The aim of this study was to analyze the prognostic value of NT-proBNP in patients with an sRV. METHODS: The prognostic value of NT-proBNP was assessed in 98 patients from the SERVE trial. We used an adjusted Cox proportional hazards model, survival analysis, and c-statistics. The composite primary outcome was the occurrence of clinically relevant arrhythmia, heart failure, or death. Correlations between baseline NT-proBNP values and biventricular volumes and function were assessed by adjusted linear regression models. RESULTS: The median age [interquartile range] at baseline was 39 [32-48] years and 32% were women. The median NT-proBNP was 238 [137-429] ng/L. Baseline NT-proBNP concentrations were significantly higher among the 20 (20%) patients developing the combined primary outcome compared with those who did not (816 [194-1094] vs 205 [122-357]; P = .003). In patients with NT-proBNP concentrations > 75th percentile (> 429 ng/L), we found an exponential increase in the sex- and age-adjusted hazard ratio for the primary outcome. The prognostic value of NT-proBNP was comparable to right ventricular ejection fraction and peak oxygen uptake on exercise testing (c-statistic: 0.71, 0.72 and 0.71, respectively). CONCLUSIONS: In patients with sRVs, NT-proBNP concentrations correlate with sRV volumes and function and may serve as a simple tool for predicting adverse outcomes.

Prognostic Value and Determinants of High-Sensitivity Cardiac Troponin T in Patients With a Systemic Right Ventricle: Insights From the SERVE Trial.

BACKGROUND: The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown. METHODS AND RESULTS: Ninety-eight patients from the randomized controlled SERVE (Effect of Phosphodiesterase-5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs-cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs-cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all-cause death. Median age was 39 (interquartile range, 32-48) years, and 32% were women. Median hs-cTnT concentration was 7 (interquartile range, 4-11) ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 (P=0.046) and -0.381 (P=0.018), respectively. The sex- and age-adjusted hazard ratio for the primary outcome of hs-cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14-7.29) and 4.42 (95% CI, 1.21-16.15), respectively. The prognostic performance quantified by the concordance statistics for age- and sex-adjusted models based on hs-cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61-0.82), 0.72% (95% CI, 0.59-0.84), and 0.71% (95% CI, 0.59-0.83), respectively. CONCLUSIONS: Hs-cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end-systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs-cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03049540.

Ketamine vs. haloperidol for prevention of cognitive dysfunction and postoperative delirium: A phase IV multicentre randomised placebo-controlled double-blind clinical trial.

STUDY OBJECTIVE: Delirium is frequently observed in the postoperative and intensive care unit (ICU) population. Due to the multifactorial origin of delirium and according to international guidelines (e.g., American Geriatrics Society; Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) guideline), there are several but no incontestable options for prevention and symptomatic treatment. The purpose of the Baden PRIDe (Prevention and Reduction of Incidence of postoperative Delirium) trial was to determine whether postoperative cognitive dysfunction and delirium could be prevented by the combination of possible preventive agents such as haloperidol and ketamine. In addition, pre- and postoperative levels of the biomarkers cortisol, neuron specific enolase (NSE) and S100ß were measured to investigate their dynamics in delirious and non-delirious patients after surgery. DESIGN: The Baden PRIDe Trial was an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial. SETTING: Perioperative care. PATIENTS: 182 adult patients that underwent elective or emergency surgery under general or combined (i.e., general and regional) anaesthesia. INTERVENTIONS: Pre-anaesthetic, pharmacologic prevention of postoperative brain dysfunction with haloperidol, ketamine, and the combination of both vs. placebo. MEASUREMENTS: Assessment of cognitive performance pre- and postoperatively with the MMSE, the DOS, the Nursing Delirium Screening Scale (Nu-DESC) or the Intensive Care Delirium Screening Checklist (ICDSC) during ICU stay. MAIN RESULTS: None of the three study arms - haloperidol, ketamine, or both drugs combined - was significantly superior to placebo for prevention of postoperative brain dysfunction and delirium (P = 0.39). Measured levels of postoperative cortisol were significantly higher in delirious patients. S-100ß levels were significantly higher in all postoperative outcome groups (cognitive impairment, delirium, no cognitive decline), whereas postoperative NSE levels declined in all groups. CONCLUSIONS: The study results offer no possibility for a novel recommendation for prevention of postoperative cognitive decline including delirium. Perioperative S-100ß trajectories in patients with cognitive deterioration suggest affection of glial cells in particular. TRIAL REGISTRATION: ClinicalTrials.govNCT02433041; registered on April 7, 2015.

Study protocol for a prospective randomised double-blind placebo-controlled clinical trial investigating a Better Outcome with Melatonin compared to Placebo Administered to normalize sleep-wake cycle and treat hypoactive ICU Delirium: the Basel BOMP-AID study.

INTRODUCTION: Delirium is frequently observed in the intensive care unit (ICU) population, in particular. Until today, there is no evidence for any reliable pharmacological intervention to treat delirium. The Basel BOMP-AID (Better Outcome with Melatonin compared to Placebo Administered to normalize sleep-wake cycle and treat hypoactive ICU Delirium) randomised trial targets improvement of hypoactive delirium therapy in critically ill patients and will be conducted as a counterpart to the Basel ProDex Study (Study Protocol, BMJ Open, July 2017) on hyperactive and mixed delirium. The aim of the BOMP-AID trial is to assess the superiority of melatonin to placebo for the treatment of hypoactive delirium in the ICU. The study hypothesis is based on the assumption that melatonin administered at night restores a normal circadian rhythm, and that restoration of a normal circadian rhythm will cure delirium. METHODS AND ANALYSIS: The Basel BOMP-AID study is an investigator-initiated, single-centre, randomised controlled clinical trial for the treatment of hypoactive delirium with the once daily oral administration of melatonin 4 mg versus placebo in 190 critically ill patients. The primary outcome measure is delirium duration in 8-hour shifts. Secondary outcome measures include delirium-free days and death at 28 days after study inclusion, number of ventilator days, length of ICU and hospital stay, and sleep quality. Patients will be followed after 3 and 12 months for activities of daily living and mortality assessment. Sample size was calculated to demonstrate superiority of melatonin compared with placebo regarding the duration of delirium. Results will be presented using an intention-to-treat approach. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonisation (ICH) of technical requirements for registration of pharmaceuticals for human use; Good Clinical Practice (GCP) or ISO EN 14155 (as far as applicable), as well as all national legal and regulatory requirements. Study results will be presented in international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03438526. PROTOCOL VERSION: Clinical Study Protocol Version 3, 10.03.2019.