Observational cohort study of ventricular arrhythmia in adults with Marfan syndrome caused by FBN1 mutations
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Observational cohort study of ventricular arrhythmia in adults with Marfan syndrome caused by FBN1 mutations. / Aydin, Ali; Adsay, Baran A; Sheikhzadeh, Sara; Keyser, Britta; Rybczynski, Meike; Sondermann, Claudia; Detter, Christian; Steven, Daniel; Robinson, Peter N; Berger, Jürgen; Schmidtke, Jörg; Blankenberg, Stefan; Willems, Stephan; von Kodolitsch, Yskert; Hoffmann, Boris A.
in: PLOS ONE, Jahrgang 8, Nr. 12, 2013, S. e81281.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Observational cohort study of ventricular arrhythmia in adults with Marfan syndrome caused by FBN1 mutations
AU - Aydin, Ali
AU - Adsay, Baran A
AU - Sheikhzadeh, Sara
AU - Keyser, Britta
AU - Rybczynski, Meike
AU - Sondermann, Claudia
AU - Detter, Christian
AU - Steven, Daniel
AU - Robinson, Peter N
AU - Berger, Jürgen
AU - Schmidtke, Jörg
AU - Blankenberg, Stefan
AU - Willems, Stephan
AU - von Kodolitsch, Yskert
AU - Hoffmann, Boris A
PY - 2013
Y1 - 2013
N2 - BACKGROUND: Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation.METHODS AND RESULTS: We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years) with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h), as ventricular couplets (Couplet), or as non-sustained ventricular tachycardia (nsVT), and during 31±18 months of follow-up as ventricular tachycardia (VT) events (VTE) such as sudden cardiac death (SCD), and sustained ventricular tachycardia (sVT). We identified >10 PVC/h in 28 (35%), Couplet/nsVT in 32 (40%), and VTE in 6 patients (8%), including 3 with SCD (4%). PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro-brain natriuretic peptide serum levels(P<.001). All arrhythmias related to increased NT-proBNP (P<.001), where PVC>10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020), to moderate mitral valve regurgitation (P = .018 and P = .003), and to prolonged QTc intervals (P = .001 and P = .006), respectively. Moreover, VTE related to mutations in exons 24-32 (P = .021). Kaplan-Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001) and with mutations in exons 24-32 (P<.001).CONCLUSIONS: Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors of VTE.
AB - BACKGROUND: Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation.METHODS AND RESULTS: We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years) with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h), as ventricular couplets (Couplet), or as non-sustained ventricular tachycardia (nsVT), and during 31±18 months of follow-up as ventricular tachycardia (VT) events (VTE) such as sudden cardiac death (SCD), and sustained ventricular tachycardia (sVT). We identified >10 PVC/h in 28 (35%), Couplet/nsVT in 32 (40%), and VTE in 6 patients (8%), including 3 with SCD (4%). PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro-brain natriuretic peptide serum levels(P<.001). All arrhythmias related to increased NT-proBNP (P<.001), where PVC>10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020), to moderate mitral valve regurgitation (P = .018 and P = .003), and to prolonged QTc intervals (P = .001 and P = .006), respectively. Moreover, VTE related to mutations in exons 24-32 (P = .021). Kaplan-Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001) and with mutations in exons 24-32 (P<.001).CONCLUSIONS: Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors of VTE.
KW - Adult
KW - Arrhythmias, Cardiac/genetics
KW - Death, Sudden, Cardiac/pathology
KW - Electrocardiography, Ambulatory
KW - Exons/genetics
KW - Female
KW - Fibrillin-1
KW - Fibrillins
KW - Humans
KW - Kaplan-Meier Estimate
KW - Male
KW - Marfan Syndrome/genetics
KW - Microfilament Proteins/genetics
KW - Middle Aged
KW - Mutation
KW - Natriuretic Peptide, Brain/genetics
KW - Peptide Fragments/genetics
KW - Tachycardia, Ventricular/genetics
U2 - 10.1371/journal.pone.0081281
DO - 10.1371/journal.pone.0081281
M3 - SCORING: Journal article
C2 - 24349050
VL - 8
SP - e81281
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 12
ER -
