{"id":"29114687de07","type":"article","url":"https://hartvaat.nl/2026/03/06/laminopathieen-natuurlijk-beloop-en-voorspelmodel-voor-hartfalen/","title":"Laminopathieën: natuurlijk beloop en voorspelmodel voor hartfalen","title_en":"Laminopathies: natural history and risk prediction of heart failure.","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog"],"tags":["acuut-hartfalen","cardiomyopathie-gerichte-therapie","gedilateerde-cardiomyopathie","harttransplantatie","hfref","hypertrofische-cardiomyopathie","laminopathie","nt-probnp","pathfinder-trial","step-hfpef","vrouwen"],"journal":"European heart journal","doi":"10.1093/eurheartj/ehag104","source_url":"https://doi.org/10.1093/eurheartj/ehag104","authors":["Philippe Charron","Julie Proukhnitzky","Rabah Ben Yaou","Pascale Richard","Mohamed Dembélé","Mario Urtis","Thomas Gossios","Saurabh Kumar","Konstantinos Savvatis","Tanya Stojkovic","Frédéric Anselme","Philippe Maury","Estelle Gandjbakhch","Raphaël Martins","Frédéric Sacher","Jean-Noel Trochu","Stéphanie Rouanet","Julie Lejeune","Ghassan Moubarak","Abdallah Fayssoil","Eloi Marijon","Pascal Laforêt","Anthony Béhin","Sarah Leonard-Louis","Guilhem Sole","Fabien Labombarda","Corinne Metay","Susana Quijano-Roy","Ivana Dabaj","Didier Klug","Gilbert Habib","Marie-Christine Vantyghem","Philippe Chevalier","Emmanuelle Salort-Campana","Jean-Marc Sellal","Xavier Waintraub","Katja Zeppenfeld","Ahmad S Amin","Daria R Kramarenko","Yigal M Pinto","Andrew Landstrom","Alessandra Serio","Cathy Chikhaoui","Nicolas Combes","Christine Barnerias","Henri-Marc Bécane","Eric Bieth","Franck Boccara","Damien Bonnet","Françoise Bouhour","Anne-Claire Brehin","Pascal Cintas","François Roubille","Nicolas Lamblin","Pascal de Groote","Pierre-Francois Winum","Nicolas Piriou","Patricia Réant","Annachiara De Sandre-Giovannoli","Marion Masingue","Isabelle Desguerre","Julien Durigneux","Andoni Echaniz-Laguna","Romain Eschalier","Ana Ferreiro","Mélanie Fradin","Bénédicte Gaborit","Arnaud Gay","Albert Hagège","Arnaud Isapof","Isabelle Jeru","Emmanuelle Lagrue","Vincent Laugel","Arnaud Lazarus","France Leturcq","Armelle Magot","Véronique Manel","Sandra Mercier","Christophe Meune","Maud Michaud","Marie-Christine Minot-Myhié","Aleksandra Nadaj-Pakleza","Yann Péréon","Florence Petit","Julien Praline","Anne Rollin","Catherine Sarret","Frederic Taithe","Céline Tard","Vincent Tiffreau","Laurent Fauchier","Camille Vatier","Ulrike Walther-Louvier","Benjamin Schurr","Pierre Bobin","Mohamed El Hachmi","Clarisse Billon","Bertrand Fontaine","Corinne Vigouroux","Neal K Lakdawala","Eloisa Arbustini","Perry Elliott","Gisèle Bonne","Karim Wahbi"],"significance":7,"published":"2026-03-21","source_date":"2026-03-06","image":"","kennis":["https://hartvaat.nl/kennis/hartfalen/palliatief-hartfalen/"],"congress":"","summary_en":"This large EHJ study of 470 patients with LMNA gene variants characterized the risk of severe heart failure in laminopathies and developed a prediction model to guide surveillance and early intervention in this high-risk genetic cardiomyopathy.","created":"2026-07-03T10:32:36Z","updated":"2026-07-03T18:39:28Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"In deze grote EHJ-studie werd bij 470 patiënten met LMNA-genvarianten het risico op ernstig hartfalen in kaart gebracht. De onderzoekers ontwikkelden een voorspelmodel dat cardiologen kan helpen bij de risicostratificatie en het bepalen van het behandelbeleid bij deze hoogrisicopopulatie met gedilateerde cardiomyopathie.","abstract_original":"BACKGROUND AND AIMS: Patients with LMNA gene variants are at high risk for dilated cardiomyopathy and heart failure (HF), but no prediction model for severe HF events exists. This study aimed to describe the incidence of severe HF events and develop a prediction model in a large cohort of patients with adult-onset laminopathies. METHODS: From a population of 660 patients enrolled in the French LMNA nationwide registry, 470 adults were included in the derivation cohort. An independent international validation cohort included 245 additional patients. Baseline characteristics at genetic testing were assessed and the cumulative incidence of the primary endpoint HF-major adverse cardiac events (HF-MACE) was calculated, defined as HF hospitalization, HF-related death, mechanical circulatory support, or heart transplantation. Predictors of HF-MACE were studied after excluding patients with left ventricular ejection fraction (LVEF) <30% at baseline using a Fine-Gray competing risk model, adjusted hazard ratio (aHR) with 95% confidence interval (CI), and Harrell's concordance (C-) index. A secondary composite endpoint, without hospitalization, was also studied. RESULTS: Among 470 patients of the derivation cohort, HF-MACE occurred in 65 over a median follow-up of 7.1 years (interquartile range: 3.4-12.1). Four independent predictors of HF-MACE were identified: male sex (aHR 1.86; 95% CI 1.060-3.290), LVEF <50% (aHR 2.18; 95% CI 1.080-4.400), missense variants in head and rod domains (aHR 2.91; 95% CI 1.110-7.630), and complete left bundle branch block (aHR 2.99; 95% CI 1.400-6.400). The C-index of the model was 0.750 (95% CI 0.720-0.780) in the derivation cohort and 0.758 (95% CI 0.720-0.800) in the validation cohort. The 5-year cumulative incidence of HF-MACE was 1.5% (95% CI 0.6-3.6), 5.0% (95% CI 1.8-8.2), and 22.0% (95% CI 15.6-28.4) among patients with 0, 1, and ≥2 risk factors, respectively. In patients with LVEF <30% at baseline, the 1-year incidence of HF-MACE was 50%, and those patients were excluded from the risk score. CONCLUSIONS: The first prediction model for severe HF events in adult laminopathies was developed, which may facilitate early and optimal preventive management. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov Unique identifier: NCT03058185."}