Prognostic value of myocardial fibrosis in severe aortic stenosis: study protocol for a prospective observational multi-center study (FIB-AS)

Giedrė Balčiūnaitė, Darius Palionis, Edvardas Žurauskas, Viktor Skorniakov, Vilius Janušauskas, Aleksejus Zorinas, Tomas Zaremba, Nomeda Valevičienė, Audrius Aidietis, Pranas Šerpytis, Kęstutis Ručinskas, Peter Sogaard, Sigita Glaveckaitė, Giedrė Balčiūnaitė, Darius Palionis, Edvardas Žurauskas, Viktor Skorniakov, Vilius Janušauskas, Aleksejus Zorinas, Tomas Zaremba, Nomeda Valevičienė, Audrius Aidietis, Pranas Šerpytis, Kęstutis Ručinskas, Peter Sogaard, Sigita Glaveckaitė

Abstract

Background: Adverse cardiac remodeling with a myocardial fibrosis as a key pathophysiologic component may be associated to worse survival in aortic stenosis (AS) patients. Therefore, with the application of advanced cardiac imaging we aim to investigate left ventricular myocardial fibrosis in severe AS patients undergoing aortic valve replacement (AVR) and determine its impact with post-intervention clinical outcomes.

Methods: In a prospective, observational, cohort study patients with severe AS scheduled either for surgical or transcatheter AVR will be recruited from two tertiary heart centers in Denmark and Lithuania. All patients will receive standard of care in accordance with the current guidelines and will undergo additional imaging testing before and after AVR: echocardiography with deformation analysis and cardiovascular magnetic resonance (CMR) with T1 parametric mapping. Those undergoing surgical AVR will also have a myocardial biopsy sampled at the time of a surgery for histological validation. Patients will be recruited over a 2-year period and followed up to 2 years to ascertain clinical outcomes. Follow-up CMR will be performed 12 months following AVR, and echocardiography with deformation analysis will be performed 3, 12, and 24 months following AVR. The study primary outcome is a composite of all-cause mortality and major adverse cardiovascular events.

Discussion: Despite continuous effort of research community there is still a lack of early predictors of left ventricular decompensation in AS, which could improve patient risk stratification and guide the optimal timing for aortic valve intervention, before irreversible left ventricular damage occurs. Advanced cardiac imaging and CMR derived markers of diffuse myocardial fibrosis could be utilized for this purpose. FIB-AS study is intended to invasively and non-invasively assess diffuse myocardial fibrosis in AS patients and investigate its prognostic significance in post-interventional outcomes. The results of the study will expand the current knowledge of cardiac remodeling in AS and will bring additional data on myocardial fibrosis and its clinical implications following AVR.

Ethics/dissemination: The study has full ethical approval and is actively recruiting patients. The results will be disseminated through scientific journals and conference presentations.

Trial registration: ClinicalTrials.govNCT03585933. Registered on 02 July 2018.

Keywords: Aortic valve replacement; Aortic valve stenosis; Magnetic resonance imaging; Myocardial fibrosis; Prognosis.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of FIB-AS study. Abbreviations: 6MWT- 6-min walking test, AS- aortic stenosis, BNP- brain natriuretic peptide, CAD- coronary artery disease, LGE-CMR- late gadolinium enhancement cardiovascular magnetic resonance, MLHFQ- Minnesota Living with Heart Failure Questionnaire, SAVR- surgical aortic valve replacement, VHD- valvular heart disease, TAVR- transcatheter aortic valve replacement, Tn-I- troponin I
Fig. 2
Fig. 2
CMR T1 assessment. To measure the T1 value, regions of interest will be drawn manually in the blood and septum at the midventricular level on the short-axis, avoiding papillary muscle
Fig. 3
Fig. 3
CMR protocol for FIB-AS study
Fig. 4
Fig. 4
Standard protocol items: recommendation for interventional trials (SPIRIT) figure of participant timeline. Abbreviations: 2D- two-dimensional, 6MWT- 6-min walking test, CMR- cardiovascular magnetic resonance, MACEs- major adverse cardiovascular events, m- months, MLHFQ- Minnesota Living with Heart Failure Questionnaire. *Endomyocardial biopsy will be performed only in patients undergoing surgical AVR

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