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

Yasuhiro Yokoyama, Naoya Kataoka, Michikazu Nakai, Ayaka Matsuo, Akihiro Fujiwara, Akinori Wakamiya, Nobuhiko Ueda, Kenzaburo Nakajima, Tsukasa Kamakura, Mitsuru Wada, Kenichiro Yamagata, Kohei Ishibashi, Yuko Inoue, Koji Miyamoto, Satoshi Nagase, Takashi Noda, Takeshi Aiba, Hiroyuki Takahama, Chisato Izumi, Koichiro KinugawaNaoto Minamino, Kengo Kusano

Research output: Contribution to journalArticlepeer-review


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).

Original languageEnglish
Pages (from-to)727-733
Number of pages7
JournalJournal of cardiology
Issue number6
Publication statusPublished - 2022 Jun
Externally publishedYes


  • Brain/B-type natriuretic peptide
  • Cardiac resynchronization therapy
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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