Abstract
BackgroundAortic root dilatation and—dissection and mitral valve prolapse are established cardiovascular manifestations in Marfan syndrome (MFS). Heart failure and arrhythmic sudden cardiac death have emerged as additional causes of morbidity and mortality.MethodsTo characterize myocardial dysfunction and arrhythmia in MFS we conducted a prospective longitudinal case–control study including 86 patients with MFS (55.8% women, mean age 36.3 yr—range 13–70 yr–) and 40 age—and sex-matched healthy controls. Cardiac ultrasound, resting and ambulatory ECG (AECG) and NT-proBNP measurements were performed in all subjects at baseline. Additionally, patients with MFS underwent 2 extra evaluations during 30 ± 7 months follow-up. To study primary versus secondary myocardial involvement, patients with MFS were divided in 2 groups: without previous surgery and normal/mild valvular function (MFS-1; N = 55) and with previous surgery or valvular dysfunction (MFS-2; N = 31).ResultsCompared to controls, patients in MFS-1 showed mild myocardial disease reflected in a larger left ventricular end-diastolic diameter (LVEDD), lower TAPSE and higher amount of (supra) ventricular extrasystoles [(S)VES]. Patients in MFS-2 were more severely affected. Seven patients (five in MFS-2) presented decreased LV ejection fraction. Twenty patients (twelve in MFS-2) had non-sustained ventricular tachycardia (NSVT) in at least one AECG. Larger LVEDD and higher amount of VES were independently associated with NSVT.ConclusionOur study shows mild but significant myocardial involvement in patients with MFS. Patients with previous surgery or valvular dysfunction are more severely affected. Evaluation of myocardial function with echocardiography and AECG should be considered in all patients with MFS, especially in those with valvular disease and a history of cardiac surgery.
Highlights
Marfan syndrome (MFS) (OMIM #154700, ORPHA #284963) is an inherited connective tissue disorder caused by pathogenic variants in the fibrillin-1 gene (FBN1), encoding for the extracellular matrix protein, fibrillin-1 [1]
Left ventricular enlargement and myocardial dysfunction in MFS can result from valvular disease, but primary biventricular myocardial involvement in patients with MFS without valvular pathology has been shown by several independent groups [5,6,7,8,9,10]
Eleven patients had moderate to severe valvular disease (5 mitral valve regurgitation, 4 aortic valve regurgitation and 1 both) of whom 7 had not undergone cardiovascular surgery
Summary
Marfan syndrome (MFS) (OMIM #154700, ORPHA #284963) is an inherited connective tissue disorder caused by pathogenic variants in the fibrillin-1 gene (FBN1), encoding for the extracellular matrix protein, fibrillin-1 [1]. Aortic root dilatation and—dissection and mitral valve prolapse (MVP) are the most common and best studied cardiovascular manifestations in MFS, heart failure and sudden cardiac death, presumably secondary to ventricular arrhythmia, seem to be additional causes of morbidity and mortality to consider in at least some of these patients [2, 3]. Mild myocardial impairment and abnormal myocardial signaling have been shown in 2 different murine models of MFS (fbn1mgR/ mgR and fbn C1039G/+) [13, 14] Using one of these models (fbn C1039G/+), Rouff et al [15] further showed that hemodynamic overload by TAC ligation (transverse aortic constriction), was less well tolerated in MFS mice than in wild-type littermates. Heart failure and arrhythmic sudden cardiac death have emerged as additional causes of morbidity and mortality
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