BIOmarker Based Diagnostic TOOLkit to Personalize Pharmacological Approaches in Congestive Heart Failure

IRCCS Azienda Ospedaliero-Universitaria di Bologna4,254 enrolled

Overview

This retrospective study will take advantage of an existing EU-funded dataset, the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), which was designed to identify biomarkers related to the response to guideline directed medical therapy, and coordinated by UMCG. The availability of this comprehensive dataset of patients with severe HFrEF, prospectively and consistently collected, with the possibility to access a biobank to re-assay samples with novel biomarkers, provides a unique opportunity to derive preliminary data about the interaction between biomarkers of congestion and diuretic doses, that were prescribed based on clinical judgement, and therefore derive a machine learning-based algorithm than could be tested to guide the management of diuretic therapy

This is a retrospective study based on the index and the validation cohorts of the BIOSTAT-CHF project. The index cohort consists of a prospectively enrolled series of 2516 patients from 69 centres in 11 European countries recruited between December 2010 and December 2012 and with a median follow-up of 21 months \[interquartile range (IQR) 15 - 27 months\]. Validation cohort was designed as well as a multicentre, prospective, observational study, which included 1738 patients from six centres in Scotland, United Kingdom. BIOSTAT-CHF data will be re-analysed to include additional congestion biomarkers and derive a predictive model for congestion-related adverse events at 9 months after study entry, priming the design of a prospective randomized study. Predictive models based on the analysis of the BIOSTAT-CHF cohort had already been reported. When considering only standard clinical and biological predictive variables, the full prediction models for mortality, hospitalisation owing to HF, and the combined outcome, yielded c-statistic values of 0.73, 0.69, and 0.71, respectively. The five strongest predictors of mortality were more advanced age, higher blood urea nitrogen and N-terminal pro-B-type natriuretic peptide (NT-proBNP), lower haemoglobin, and failure to prescribe a beta-blocker. The five strongest predictors of hospitalisation due to decompensated HF were more advanced age, previous hospitalisation owing to HF, presence of oedema, lower systolic blood pressure and lower estimated glomerular filtration rate. We hypothesize that by including a more granular biomarkers analysis and different statistical models, the BIOSTAT-DISCO may provide a multi-parametric score that can be tested to guide therapy management.

Study Type

OBSERVATIONAL

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: In order to have been included to participate in the index trial, a subject must have met all of the following criteria: age \>=18 years with symptoms of new-onset or worsening heart failure; objective evidence of cardiac dysfunction documented either by left ventricular ejection fraction \<=40% or plasma concentrations of brain natriuretic peptide (BNP) \>400 pg/mL and/or NT-proBNP \>2000 pg/mL; treatment with either oral or intravenous furosemide \>=40 mg/day or equivalent at the time of inclusion; not previously treated with evidence-based therapies (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers) or receiving \<=50% of target doses of these drugs at the time of inclusion; anticipated initiation or up-titration of ACE inhibitors or ARBs and/or beta-blockers by the treating physician. For the validation cohort, patients had to fulfil the following inclusion criteria: age \>=18 years; diagnosis of heart failure with a previous documented admission requiring diuretic treatment; treatment with furosemide \>=20 mg/day or equivalent; not previously treated or receiving \<=50% of target doses of ACE inhibitors or ARBs and/or beta-blockers; anticipated initiation or up-titration of ACE inhibitors or ARBs and/or beta-blockers. In both trials, patients could be enrolled as inpatients or from outpatient clinics. Exclusion Criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: known diagnosis of septicaemia, known diagnosis of acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy, heart transplant recipient or admitted for cardiac transplantation or left ventricular assist device surgery, anticipated need for surgery or any cardiovascular intervention, except implantable cardioverter defibrillator and-or cardiac resynchronization therapy, within 4 weeks, current known inability to follow instructions or comply with follow-up procedures, and treatment with medications or devices not approved in Europe. Patients with concomitant pulmonary disease, even if severe, valvular disease, acute coronary syndrome or stroke, could be included when the primary diagnosis for admission to hospital or outpatient clinic visit was heart failure, rather than the concomitant condition

BIOmarker Based Diagnostic TOOLkit to Personalize Pharmacological Approaches in Congestive Heart Failure

Overview

Conditions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes