Differentiating heart failure phenotypes using sex‐specific transcriptomic and proteomic biomarker panels

Abstract

AimsHeart failure with preserved ejection fraction (HFpEF) accounts for 30–50% of patients with heart failure (HF). A major obstacle in HF management is the difficulty in differentiating between HFpEF and heart failure with reduced ejection fraction (HFrEF) using conventional clinical and laboratory investigations. The aim of this study is to develop robust transcriptomic and proteomic biomarker signatures that can differentiate HFpEF from HFrEF.Methods and resultsA total of 210 HF patients were recruited in participating institutions from the Alberta HEART study. An expert clinical adjudicating panel differentiated between patients with HFpEF and HFrEF. The discovery cohort consisted of 61 patients, and the replication cohort consisted of 70 patients. Transcriptomic and proteomic data were analysed to find panels of differentiating HFpEF from HFrEF. In the discovery cohort, a 22‐transcript panel was found to differentiate HFpEF from HFrEF in male patients with a cross‐validation AUC of 0.74, as compared with 0.70 for N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in those same patients. An ensemble of the transcript panel and NT‐pro‐BNP yielded a cross‐validation AUC of 0.80. This performance improvement was also observed in the replication cohort. An ensemble of the transcriptomic panel with NT‐proBNP produced a replication AUC of 0.90, as compared with 0.74 for NT‐proBNP alone and 0.73 for the transcriptomic panel.ConclusionsWe have identified a male‐specific transcriptomic biomarker panel that can differentiate between HFpEF and HFrEF. These biosignatures could be further replicated on other patients and potentially be developed into a blood test for better management of HF patients.

Natriuretic peptides for the detection of diastolic dysfunction and heart failure with preserved ejection fraction—a systematic review and meta-analysis

“…Twenty-eight were performed in Europe [ 20 , 32 – 36 , 38 , 40 , 41 , 43 – 45 , 50 , 52 , 53 , 55 – 57 , 59 , 63 , 64 , 66 , 69 , 73 , 76 – 78 ], 11 in North America [ 22 , 37 , 39 , 46 , 49 , 54 , 65 , 70 , 72 , 74 , 75 ], 11 in Asia [ 31 , 42 , 47 , 51 , 58 , 60 – 62 , 67 , 68 , 71 ] and one was a multi-country study [ 48 ]. The control populations were either healthy controls ( N = 14) [ 31 , 35 , 59 , 60 , 62 , 65 , 67 – 69 , 71 , 72 , 75 – 77 ] or were recruited at the same department as the patient population, but without DD or HFpEF ( N = 37) [ 32 – 34 , 36 – 42 , 58 , 61 , 63 , 64 , 66 , 70 ]. The mean age of the DD and HFpEF populations ranged from 51 to 74 years and...…”

“…Five DD studies included patients with HFpEF [ 38 , 43 , 48 , 73 , 76 ], one DD study included patients with signs and symptoms [ 44 ], but did not exclude on LVEF, and eight DD studies only included patients with LVEF above 45 or 50% [ 18 , 20 , 45 , 47 , 50 , 52 , 53 , 77 ]. The reference diagnoses used in the included studies varied from use of maximal velocity of the E-wave (e’) ( N = 10) [ 43 – 45 , 49 , 50 , 52 , 54 , 56 , 57 , 74 ] versus no tissue Doppler (TDI) measures ( N = 14) [ 18 , 20 , 22 , 38 , 46 – 48 , 51 , 53 , 55 , 73 , 76 – 78 ] for DD studies and, use of extensive criteria ( N = 13) [ 31 , 32 , 34 , 35 , 38 , 41 , 59 , 61 , 63 , 64 , 66 , 69 , 72 ], signs and symptoms of HF in combination with LVEF ( N = 11) [ 36 , 40 , 42 , 58 , 60 , 62 , 65 , 67 , 68 , 70 , 71 ], expert opinion ( N = 1) [ 33 ] or catheterization ( N = 3) [ …”

Biomarkers, myocardial fibrosis and co-morbidities in heart failure with preserved ejection fraction: an overview

“…Currently we are awaiting the results of a study which aims to identify new biomarkers of HFpEF progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF [ 36 ]. The result may not be a single biomarker, but rather a panel of biomarkers that identifies different pathophysiological changes, as has been used in previous studies [ 37 ]. Indeed, the Preserved and Reduced Ejection Fraction Epidemiological Regional Study (PREFERS) Stockholm HF study will enable the characterization and comparison of new onset HFpEF and HFrEF patients by using new cutting edge techniques such as advanced bioinformatics and spatial transcriptomics [ 36 ].…”

Influencing factors of NT‑proBNP level inheart failure patients with different cardiacfunctions and correlation with prognosis

“…When patients suffer from heart failure caused by various degrees of decompensation, the level of NT-proBNP secreted into ventricular cells is increased distinctly ( 17 ). High class of cardiac function reflects poor cardiac function, and is the cause of increased ventricular end-diastolic pressure, left ventricular enlargement, decreased ejection fraction ( 18 ), and increased NT-proBNP level. Although many studies on the relationship between the level of NT-proBNP and the development of heart failure have been reported ( 19 ), most patients were diagnosed based on clinical manifestations or New York Heart Function scores, and objective data were not used, especially for the LVEF evaluated by color Doppler echocardiography.…”