A new biomarker of cardiac resynchronization therapy response: cGMP to mature BNP ratio

Background: Biomarkers that can predict cardiac resynchronization therapy (CRT) response have not yet been identified. The purpose of this study was to assess whether individual measurements of four brain/B-type natriuretic peptide (BNP) forms, coupled with cyclic guanosine monophosphate (cGMP) might contribute to the prediction of echocardiographic CRT responders.

Methods: A BNP precursor (proBNP) and total BNP (= proBNP + mature BNP) were measured with newly developed kits, while an N-terminal fragment of proBNP (NT-proBNP) and cGMP were measured with commercial kits on the day before CRT implantation. Estimated mature BNP (emBNP = total BNP-proBNP), and the ratio of cGMP to each BNP form, as well as the concentrations of three other BNP forms, were prospectively investigated for their capability in predicting a response to CRT. A CRT responder was defined as an improvement in left ventricular ejection fraction >10% and/or a reduction in left ventricular end-systolic volume >15% at 6-month follow-up.

Results: Out of 77 patients, 46 (60%) were categorized as CRT responders. Among the measurement parameters, only the highest quartile of the cGMP to emBNP ratio was an independent predictor of CRT responders (odds ratio 4.87, 95% confidence interval 1.25-18.89, p = 0.02). The cGMP to emBNP ratio was associated with the cumulative events of heart failure hospitalization within one year following CRT implantation (log-rank p = 0.029).

Conclusions: The cGMP to emBNP ratio could be utilized as a predictive biomarker of CRT responders. (Clinical Study on Responder Prediction in Cardiac Resynchronization Therapy Using Individual Molecular Measurement of Natriuretic Peptide: UMIN R000038927).