Soluble suppression of tumorigenesis-2 (sST2), a new potential biomarker of response to cardiac resynchronization therapy and cardiac contractility modulation in patients with chronic heart failure

Abstract

Background: According to numerous studies, from 30% to 50% of patients with chronic heart failure (CHF) are resistant to cardiac resynchronization therapy (CRT) and cardiac contractility modulation (CCM), despite their careful selection in accordance with current guidelines. It is of interest to study neurohormones characterizing myocardial (NT-proBNP) and fibrosis (sST2) as potential additional markers of CHF patients' “response” to CRT and CCM.

Aim: To evaluate the potential to use NT-proBNP and sST2 biomarkers in CHF patients combined with transthoracic echocardiography (Echo) and contrast magnetic resonance imaging (MRI) parameters of the heart to predict a positive response to CRT and CCM devices.

Materials and methods: The study included 51 patients (41 men, 10 women) aged 58 ± 12 years (26 to 79 years) with ischemic heart disease post acute myocardial infarction (n = 22) or non-ischemic cardiomyopathy (n = 29), left ventricle (LV) ejection fraction (EF) < 35%, and CHF II–III NYHA functional class despite ≥ 3 months of optimized medical therapy. The patients were assessed by serum biomarkers NT-proBNP and sST2 measurements, transthoracic Echo, and contrast- enhanced cardiac MRI. After the diagnostic assessment, CRT defibrillators (CRT-D) were implanted to 39 patients and CCM to 12 patients. After prospective follow-up of the patients for 18 to 24 months, predictors of the response to each device type were analyzed in univariate, multivariate, and ROC analysis.

Results: The response to CRT-D was found in 21 (54%) patients, to CCM in 7 (58%) patients. Multivariate analysis showed the following predictors of the response of patients to CRT-D were: 1) sST2 < 50 ng/mL, 2) NT-proBNP < 3900 pg/mL, 3) < 3 LV segments with fibrosis (by MRI) and 4) anteroposterior dimension of the left atrium < 4.8 cm (by Echo). Any 2 of these 4 characteristics made it possible to predict the response to CRT with an accuracy of 87% (sensitivity 90%, specificity 83%). The predictors of the response to CCM were: 1) sST2 < 30 ng/ml, 2) LV end diastolic diameter < 78 mm (Echo), 3) age < 56 years, 4) body mass index < 27 kg/m2. Any 2 of these 4 characteristics predicted the positive response to CCM with an accuracy of 92% (sensitivity 86%, specificity 100%).

Conclusion: The preoperative sST2 level was the only universal marker of the response to either CRT (< 50 ng/mL) or CCM (< 30 ng/mL) devices in CHF patients with reduced LVEF. The results indicate the potential for improved efficacy of these devices with their earlier implantation after the onset of the heart disease, as well as provided that maximal control CHF in these patients has been achieved.

About the authors

N. B. Shlevkov

National Medical Research Cardiology Center

Author for correspondence.
Email: nik.shlevkov@inbox.ru
ORCID iD: 0000-0003-3956-1860

Nikolay B. Shlevkov – MD, PhD, Leading Research Fellow, Laboratory of Interventional Methods for Diagnostics and Treatment of Rhythm Disorders, Cardiac Conduction and Syncope, Department of Clinical Electrophysiology and X-ray Surgical Methods for Treatment of Heart Rhythm Disorders

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

A. Zh. Gasparyan

National Medical Research Cardiology Center

Email: doctor_gasparyan@inbox.ru
ORCID iD: 0000-0001-9984-6505

Armenui Zh. Gasparyan – Postgraduate Student, Department of Clinical Electrophysiology and X-ray 
Surgical Methods for Treatment of Heart Rhythm Disorders

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

A. A. Zhambeev

National Medical Research Cardiology Center

Email: azhambeev@yandex.ru
ORCID iD: 0000-0002-3550-6111

Azamat A. Zhambeev – Postgraduate Student, Department of Clinical Electrophysiology and X-ray Surgical Methods for Treatment of Heart Rhythm Disorders

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

H. F. Salami

National Medical Research Cardiology Center

Email: hussein_salami@mail.ru
ORCID iD: 0000-0001-9751-7767

Hussein F. Salami – MD, Cardiovascular Surgeon, Clinical Department No. 7a

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

E. V. Guseva

National Medical Research Cardiology Center

Email: gev1994@list.ru
ORCID iD: 0000-0001-6500-3649

Elena V. Guseva – Postgraduate Student, Department of Clinical Electrophysiology and X-ray Surgical Methods for Treatment of Heart Rhythm Disorders

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

G. S. Tarasovskiy

National Medical Research Cardiology Center

Email: gena80@yandex.ru
ORCID iD: 0000-0002-2143-8912

Gennady S. Tarasovskiy – MD, Cardiologist, Clinical Department No. 7a

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

T. V. Sharf

National Medical Research Cardiology Center

Email: tsharf@rambler.ru
ORCID iD: 0000-0003-1993-9264

Tatiana V. Sharf – Research Fellow

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

O. V. Stukalova

National Medical Research Cardiology Center

Email: olgastukalova@mail.ru
ORCID iD: 0000-0001-8377-2388

Olga V. Stukalova – MD, PhD, Senior Research Fellow, Department of Tomography

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

E. M. Gupalo

National Medical Research Cardiology Center

Email: eleno4ka_g@mail.ru
ORCID iD: 0000-0002-0063-5474

Elena M. Gupalo – MD, PhD, Research Fellow, Department of Clinical Electrophysiology and X-ray Surgical Methods for Treatment of Heart Rhythm Disorders

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

N. A. Mironova

National Medical Research Cardiology Center

Email: mirona01@mail.ru

Nataliya A. Mironova – MD, PhD, Senior Research Fellow, Department of Clinical Electrophysiology and X-ray Surgical Methods for Treatment of Heart Rhythm Disorders

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

A. A. Skvortsov

National Medical Research Cardiology Center

Email: skvortsov00@yandex.ru
ORCID iD: 0000-0003-2712-927X

Andrey A. Skvortsov – MD, PhD, Leading Research Fellow, Department of Myocardial Diseases and Heart Failure

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

S. P. Golitsyn

National Medical Research Cardiology Center

Email: golitsyn@mail.ru
ORCID iD: 0000-0001-9913-9974

Sergey P. Golitsyn – MD, PhD, Professor, Head of Department of Clinical Electrophysiology and X-ray Surgical Methods for Treatment of Heart Rhythm Disorders

15a 3-ya Cherepkovskaya ul., Moscow, 121552, Russian Federation

Russian Federation

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Copyright (c) 2021 Shlevkov N.B., Gasparyan A.Z., Zhambeev A.A., Salami H.F., Guseva E.V., Tarasovskiy G.S., Sharf T.V., Stukalova O.V., Gupalo E.M., Mironova N.A., Skvortsov A.A., Golitsyn S.P.

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