AIMS: Mutations in the Lamin A/C gene may cause atrioventricular block, supraventricular arrhythmias, ventricular arrhythmias (VA), and dilated cardiomyopathy. We aimed to explore the predictors and the mechanisms of VA in Lamin A/C mutation-positive subjects. METHODS AND RESULTS: We included 41 Lamin A/C mutation-positive subjects. PR-interval and occurrence of VA were recorded. Left ventricular (LV) myocardial function was assessed as ejection fraction and speckle tracking longitudinal strain by echocardiography. Magnetic resonance imaging was performed to assess fibrosis in a selection of subjects. Ventricular arrhythmias were documented in 21 patients (51%). Prolonged PR-interval was the best predictor of VA (P < 0.001). Myocardial function by strain was reduced in the interventricular septum compared with the rest of the LV segments (-16.7% vs. -18.7%, P = 0.001) and correlated to PR-interval (R = 0.41, P = 0.03). Myocardial fibrosis was found exclusively in the interventricular septum and only in patients with VA (P = 0.007). PR-interval was longer in patients with septal fibrosis compared with those without (320 ± 66 vs. 177 ± 40 ms, P < 0.001). CONCLUSION: Prolonged PR-interval was the best predictor of VA in Lamin A/C mutation-positive subjects. Electrical, mechanical, and structural cardiac properties were related in these subjects. Myocardial function was most reduced in the interventricular septum and correlated to prolonged PR-interval. Myocardial septal fibrosis was associated with prolonged PR-interval and VA. Localized fibrosis in the interventricular septum may be the mechanism behind reduced septal function, atrioventricular block and VA in Lamin A/C mutation-positive subjects.
AIMS: Mutations in the Lamin A/C gene may cause atrioventricular block, supraventricular arrhythmias, ventricular arrhythmias (VA), and dilated cardiomyopathy. We aimed to explore the predictors and the mechanisms of VA in Lamin A/C mutation-positive subjects. METHODS AND RESULTS: We included 41 Lamin A/C mutation-positive subjects. PR-interval and occurrence of VA were recorded. Left ventricular (LV) myocardial function was assessed as ejection fraction and speckle tracking longitudinal strain by echocardiography. Magnetic resonance imaging was performed to assess fibrosis in a selection of subjects. Ventricular arrhythmias were documented in 21 patients (51%). Prolonged PR-interval was the best predictor of VA (P < 0.001). Myocardial function by strain was reduced in the interventricular septum compared with the rest of the LV segments (-16.7% vs. -18.7%, P = 0.001) and correlated to PR-interval (R = 0.41, P = 0.03). Myocardial fibrosis was found exclusively in the interventricular septum and only in patients with VA (P = 0.007). PR-interval was longer in patients with septal fibrosis compared with those without (320 ± 66 vs. 177 ± 40 ms, P < 0.001). CONCLUSION: Prolonged PR-interval was the best predictor of VA in Lamin A/C mutation-positive subjects. Electrical, mechanical, and structural cardiac properties were related in these subjects. Myocardial function was most reduced in the interventricular septum and correlated to prolonged PR-interval. Myocardial septal fibrosis was associated with prolonged PR-interval and VA. Localized fibrosis in the interventricular septum may be the mechanism behind reduced septal function, atrioventricular block and VA in Lamin A/C mutation-positive subjects.
Authors: Edmond M Cronin; Frank M Bogun; Philippe Maury; Petr Peichl; Minglong Chen; Narayanan Namboodiri; Luis Aguinaga; Luiz Roberto Leite; Sana M Al-Khatib; Elad Anter; Antonio Berruezo; David J Callans; Mina K Chung; Phillip Cuculich; Andre d'Avila; Barbara J Deal; Paolo Della Bella; Thomas Deneke; Timm-Michael Dickfeld; Claudio Hadid; Haris M Haqqani; G Neal Kay; Rakesh Latchamsetty; Francis Marchlinski; John M Miller; Akihiko Nogami; Akash R Patel; Rajeev Kumar Pathak; Luis C Saenz Morales; Pasquale Santangeli; John L Sapp; Andrea Sarkozy; Kyoko Soejima; William G Stevenson; Usha B Tedrow; Wendy S Tzou; Niraj Varma; Katja Zeppenfeld Journal: J Interv Card Electrophysiol Date: 2020-10 Impact factor: 1.900
Authors: Wei Wu; Mahendra D Chordia; Barry P Hart; E Sathyajith Kumarasinghe; Min K Ji; Ajay Bhargava; Michael W Lawlor; Ji-Yeon Shin; Fusako Sera; Shunichi Homma; Antoine Muchir; Uday R Khire; Howard J Worman Journal: Bioorg Med Chem Date: 2016-12-09 Impact factor: 3.641
Authors: Antoine Bondue; Eloisa Arbustini; Anna Bianco; Michele Ciccarelli; Dana Dawson; Matteo De Rosa; Nazha Hamdani; Denise Hilfiker-Kleiner; Benjamin Meder; Adelino F Leite-Moreira; Thomas Thum; Carlo G Tocchetti; Gilda Varricchi; Jolanda Van der Velden; Roddy Walsh; Stephane Heymans Journal: Cardiovasc Res Date: 2018-08-01 Impact factor: 10.787
Authors: Edmond M Cronin; Frank M Bogun; Philippe Maury; Petr Peichl; Minglong Chen; Narayanan Namboodiri; Luis Aguinaga; Luiz Roberto Leite; Sana M Al-Khatib; Elad Anter; Antonio Berruezo; David J Callans; Mina K Chung; Phillip Cuculich; Andre d'Avila; Barbara J Deal; Paolo Della Bella; Thomas Deneke; Timm-Michael Dickfeld; Claudio Hadid; Haris M Haqqani; G Neal Kay; Rakesh Latchamsetty; Francis Marchlinski; John M Miller; Akihiko Nogami; Akash R Patel; Rajeev Kumar Pathak; Luis C Sáenz Morales; Pasquale Santangeli; John L Sapp; Andrea Sarkozy; Kyoko Soejima; William G Stevenson; Usha B Tedrow; Wendy S Tzou; Niraj Varma; Katja Zeppenfeld Journal: Europace Date: 2019-08-01 Impact factor: 5.214
Authors: Elham Kayvanpour; Farbod Sedaghat-Hamedani; Ali Amr; Alan Lai; Jan Haas; Daniel B Holzer; Karen S Frese; Andreas Keller; Katrin Jensen; Hugo A Katus; Benjamin Meder Journal: Clin Res Cardiol Date: 2016-08-30 Impact factor: 5.460
Authors: Laurence M Nunn; Luis R Lopes; Petros Syrris; Cian Murphy; Vincent Plagnol; Eileen Firman; Chrysoula Dalageorgou; Esther Zorio; Diana Domingo; Victoria Murday; Iain Findlay; Alexis Duncan; Gerry Carr-White; Leema Robert; Teofila Bueser; Caroline Langman; Simon P Fynn; Martin Goddard; Anne White; Henning Bundgaard; Laura Ferrero-Miliani; Nigel Wheeldon; Simon K Suvarna; Aliceson O'Beirne; Martin D Lowe; William J McKenna; Perry M Elliott; Pier D Lambiase Journal: Europace Date: 2015-10-25 Impact factor: 5.214
Authors: Carlos Andres Sanchez Vallejo; Carlos Daniel Rodriguez Ariza; Jose Alfredo Restrepo Urbina; Santiago Callegari Osorio Journal: Eur Heart J Case Rep Date: 2022-03-22
Authors: Laura Keil; Céleste Chevalier; Paulus Kirchhof; Stefan Blankenberg; Gunnar Lund; Kai Müllerleile; Christina Magnussen Journal: Int J Mol Sci Date: 2021-07-01 Impact factor: 5.923