Charting a roadmap for heart failure biomarker studies

Abstract

Heart failure is a syndrome with a pathophysiological basis that can be traced to dysfunction in several interconnected molecular pathways. Identification of biomarkers of heart failure that allow measurement of the disease on a molecular level has resulted in enthusiasm for their use in prognostication and selection of appropriate therapies. However, despite considerable amounts of information available on numerous biomarkers, inconsistent research methodologies and lack of clinical correlations have made bench-to-bedside translations rare and left the literature with countless publications of varied quality. There is a need for a systematic and collaborative approach aimed at definitively studying the clinical benefits of novel biomarkers. In this review, on the basis of input from academia, industry, and governmental agencies, we propose a systematized approach based on adherence to specific quality measures for studies looking to augment current prediction model or use biomarkers to tailor therapeutics. We suggest that study quality, rather than results, should determine publication and propose a system for grading biomarker studies. We outline the need for collaboration between clinical investigators and statisticians to introduce more advanced statistical methodologies into the field of biomarkers that would allow for data from a large number of variables to be distilled into clinically actionable information. Lastly, we propose the creation of a heart failure biomarker consortium that would allow for a comprehensive list of biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and hypotheses to be generated for testing in biomarker-guided trials. Such a consortium could collaborate in sharing samples to identify biomarkers, undertake meta-analyses on completed trials, and spearhead clinical trials to test the clinical utility of new biomarkers.

Keywords: biomarkers; heart failure; studies.

Figure 1. Publications Involving Heart Failure Biomarkers

The number of publications involving heart failure biomarkers has dramatically increased over the last decade. This has likely resulted from high-throughput molecular biology techniques that allow increased availability of rapid-turnaround biomarker testing and reductions in costs of analysis. The majority of these studies report associations between novel biomarkers and prognosis from heart failure.

Figure 2. Approaches to Evaluation of Novel Biomarkers in Heart Failure

The methodology depends on proposed use of biomarkers, especially whether they are for diagnosis or prognostication. IDI = integrated discrimination improvement; NRI = net reclassi fication improvement; ROC = receiver-operating characteristic.

Figure 3. Strategies for Biomarker-Guided Trials in Heart Failure

Data from Freidlin et al. (34).