Cardiovascular and non‐cardiovascular death distinction: the utility of troponin beyond N‐terminal pro‐B‐type natriuretic peptide. Findings from the BIOSTAT‐CHF study

Abstract

AimsHeart failure (HF) patients are at high-risk of cardiovascular (CV) events, including CV death. Nonetheless, a substantial proportion of these patients die from non-CV causes. Identifying patients at higher risk for each individual event may help selecting patients for clinical trials and tailoring cardiovascular therapies. The aims of the present study are to: (i) characterize patients according to CV vs. non-CV death; (ii) develop models for the prediction of the respective events; (iii) assess the models' performance to differentiate CV from non-CV death.This study included 2309 patients with HF from the BIOSTAT-CHF (a systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) study. Competing-risk models were used to assess the best combination of variables associated with each cause-specific death. Results were validated in an independent cohort of 1738 HF patients. The best model to predict CV death included low blood pressure, estimated glomerular filtration rate ≤ 60 mL/min, peripheral oedema, previous HF hospitalization, ischaemic HF, chronic obstructive pulmonary disease, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), and troponin (c-index = 0.73). The non-CV death model incorporated age > 75 years, anaemia and elevated NT-proBNP (c-index = 0.71). Both CV and non-CV death rose by quintiles of the risk scores; yet these models allowed the identification of patients in whom absolute CV death rates clearly outweigh non-CV death ones. These findings were externally replicated, but performed worse in a less severely diseased population. ConclusionsRisk models for predicting CV and non-CV death allowed the identification of patients at higher absolute risk of dying from CV causes (vs. non-CV ones). Troponin helped in predicting CV death only, whereas NT-proBNP helped in the prediction of both CV and non-CV death. These findings can be useful both for tailoring therapies and for patient selection in HF trials in order to attain CV event enrichment.

It is time for consistency in the use of biomarkers in heart failure clinical trials

“…In the present issue of the Journal, Ferreira and colleagues report results from a substudy out of the BIOSTAT‐CHF (A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) trial . In this analysis, the investigators sought to develop risk models to predict cardiovascular and non‐cardiovascular events.…”

“…The ability of biomarkers such as hs‐cTnT to predict risk allows for enrolment of study patients with higher event rates, minimizing Type II error in underpowered studies, as elevated concentrations are associated with worse prognosis . And so, as Ferreira and colleagues demonstrated, a clinical trialist interested in cardiovascular death as a clinical trial endpoint may opt to use hs‐cTnT concentrations as an inclusion criterion in combination with BNP and NT‐proBNP. The potential for use of biomarker inclusion criteria concentration to attain a certain event rate is vast, and intuition would tell us that higher concentration cut‐offs are associated with higher event rates, but this has yet to be examined across the universe of HF clinical trials.…”

“…In the present issue of the Journal, Ferreira and colleagues report results from a substudy out of the BIOSTAT-CHF (A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) trial. 2 In this analysis, the investigators sought to develop risk models to predict cardiovascular and non-cardiovascular events. Both models included clinical and laboratory variables; and interestingly, both models incorporated NT-proBNP, however, high-sensitivity cardiac troponin T (hs-cTnT) helped predict cardiovascular death only.…”

Heart failure in the last year: progress and perspective

“…NPs, along with troponin, are the most useful biomarkers to predict outcomes in both chronic and acute HF to date 109–112 . NT‐proBNP is also predictive for non‐CV death 113 . The role of mid‐regional pro‐atrial natriuretic peptide has been recently investigated not only in the acute setting but also in chronic HF, and it has a diagnostic value similar to NT‐proBNP 114 …”

January 2020 at a glance: translational medicine, predictors of outcome and treatments

“…They found changes in the proteins related to the glutathione, arginine and proline, and pyruvate metabolism in the patients who died or were rehospitalized, compared with those with a stable clinical course. Ferreira et al . used biomarker analysis to compare mechanisms related to cardiovascular (CV) and non‐CV death in 2309 patients with HF from the BIOSTAT‐CHF (a systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) study.…”