Increased levels of sST2 in patients with mitral annulus disjunction and ventricular arrhythmias

Abstract

ObjectiveDisplacement of the mitral valve, mitral annulus disjunction (MAD), is described as a possible aetiology of sudden cardiac death. Stress-induced fibrosis in the mitral valve apparatus has been suggested as the underlying mechanism. We aimed to explore the association between stretch-related and fibrosis-related biomarkers and ventricular arrhythmias in MAD. We hypothesised that soluble suppression of tumourigenicity-2 (sST2) and transforming growth factor-β1 (TGFβ1) are markers of ventricular arrhythmias in patients with MAD.MethodsWe included patients with ≥1 mm MAD on cardiac MRI. We assessed left ventricular ejection fraction (LVEF) and fibrosis by late gadolinium enhancement (LGE). The occurrence of ventricular arrhythmia, defined as aborted cardiac arrest, sustained or non-sustained ventricular tachycardia, was retrospectively assessed. We assessed circulating sST2 and TGFβ1 levels.ResultsWe included 72 patients with MAD, of which 22 (31%) had ventricular arrhythmias. Patients with ventricular arrhythmias had lower LVEF (60 % (±6) vs 63% (±6), p = 0.04), more frequently papillary muscle fibrosis (14 (64%) vs 10 (20%), p < 0.001) and higher sST2 levels (31.6 ± 10.1 ng/mL vs 25.3 ± 9.2 ng/mL, p = 0.01) compared with those without, while TGFβ1 levels did not differ (p = 0.29). Combining sST2 level, LVEF and papillary muscle fibrosis optimally detected individuals with arrhythmia (area under the curve 0.82, 95% CI 0.73 to 0.92) and improved the risk model (p < 0.05) compared with single parameters.ConclusionCirculating sST2 levels were higher in patients with MAD and ventricular arrhythmias compared with arrhythmia-free patients. Combining sST2, LVEF and LGE assessment improved risk stratification in patients with MAD.

Need for expertise in mitral valve regurgitation

“…sST2 is an interleukin 1 receptor family member secreted by cardiac cells in circumstances of biomechanical stress that can promote myocardial fibrosis. In the present work, sST2 was enhanced in patients with MAD and ventricular arrhythmias (p=0.01) and improved the differentiation of patients with and without ventricular arrhythmia in conjunction with LV, EF and papillary muscles LGE 11…”

Malignant Arrhythmic Mitral Valve Prolapse: A Continuum of Clinical Challenges from Diagnosis to Risk Stratification and Patient Management

“…A familial distribution of MVP has been largely documented especially in Barlow’s patients [ 16 , 17 ] and four genes are known so far to be linked to MVP; interestingly, also an association of isolated MVP and mutations in cardiomyopathy genes was observed, further supporting the important role of myocardial involvement in the disease [ 18 , 19 ]. Finally, the possibility of testing specific biomarkers might be offered in the future; for example, initial observations showed the soluble suppression of tumourigenicity-2-serum level (sST2), as a marker of the stretched myocardium, to be higher in patients with mitral annular disjunction and VA [ 20 ].…”

Handling of Ventricular Fibrillation in the Emergency Setting

“…In contrary to the study of Patton et al, they found normal NT-proBNP and CRP levels in their population. In the same study TGFß1 was assumed to be responsible for the ventricular arrhythmogeneity (Scheirlynck et al, 2019). In the Physicians' Health Study a positive correlation was reported between high serum CRP levels and increased arrhythmia risk vulnerability, however in the Nurse's Health Study population similar connection could not be proven (Balla et al, 2019).…”