Journal of the American Heart Association · 2025
Variant-Specific Late Gadolinium Enhancement Patterns Influence Clinical Outcomes in LMNA-Related Cardiomyopathy.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Castrichini Matteo, Garmany Ramin, Siontis Konstantinos C, Collins Jeremy D, Bois John P, Pereira Naveen L, Tester David J, Gluscevic Martina, Huynh Trung, Neves Raquel, Rosenbaum Andrew N, Ackerman Michael J, Giudicessi John R
Аннотация
BACKGROUND: Disease-causative variants in LMNA-encoded lamin A/C cause a genetic cardiomyopathy characterized by atrioventricular block, atrial fibrillation, ventricular arrhythmias, and systolic dysfunction. The influence of LMNA variant type/localization on late gadolinium enhancement (LGE) patterns and clinical outcomes remains unclear.
METHODS: Retrospective analysis of 822 genotype-positive patients with arrhythmogenic/dilated cardiomyopathy was used to identify those with disease-causative variants in LMNA. Data on LGE distribution and prevalence of advanced heart failure, thromboembolic and sudden cardiac death/major ventricular arrhythmia events were extracted from the electronic record and analyzed by variant type/localization.
RESULTS: Among the 72/116 (62%) LMNA variant-positive patients with cardiac magnetic resonance imaging data, LGE was observed in 40/72 (56%) cases. Most exhibited a nonischemic, midmyocardial or subepicardial pattern (73%), and 6/40 (15%) showed a unique "pseudo-infarct" transmural pattern, predominantly affecting the apical segments. All 6 patients with this distinct LGE pattern harbored C-terminal IgD (immunoglobulin-like domain) variants (p.Arg471His or p.Arg541His). In patients with clinically manifest disease (76/116), those with IgD-localizing variants had a lower prevalence of atrioventricular block (25% versus 72%, P=0.002) and atrial fibrillation (50% versus 81%, P=0.019) but higher rates of thromboembolic events (42% versus 16%, P=0.038). During a median follow-up of 37 months, IgD variant presence independently predicted sudden cardiac death/major ventricular arrhythmia (hazard ratio, 2.391 [95% CI, 1.046-5.464]; P=0.039).
CONCLUSIONS: LMNA missense variants localizing to IgD present a distinct apical pseudo-infarct LGE pattern associated with increased risk of ventricular arrhythmias and thromboembolic events but reduced atrioventricular block and atrial fibrillation. Multicenter studies are warranted to develop variant-specific risk-stratification strategies in cardiac laminopathy.
METHODS: Retrospective analysis of 822 genotype-positive patients with arrhythmogenic/dilated cardiomyopathy was used to identify those with disease-causative variants in LMNA. Data on LGE distribution and prevalence of advanced heart failure, thromboembolic and sudden cardiac death/major ventricular arrhythmia events were extracted from the electronic record and analyzed by variant type/localization.
RESULTS: Among the 72/116 (62%) LMNA variant-positive patients with cardiac magnetic resonance imaging data, LGE was observed in 40/72 (56%) cases. Most exhibited a nonischemic, midmyocardial or subepicardial pattern (73%), and 6/40 (15%) showed a unique "pseudo-infarct" transmural pattern, predominantly affecting the apical segments. All 6 patients with this distinct LGE pattern harbored C-terminal IgD (immunoglobulin-like domain) variants (p.Arg471His or p.Arg541His). In patients with clinically manifest disease (76/116), those with IgD-localizing variants had a lower prevalence of atrioventricular block (25% versus 72%, P=0.002) and atrial fibrillation (50% versus 81%, P=0.019) but higher rates of thromboembolic events (42% versus 16%, P=0.038). During a median follow-up of 37 months, IgD variant presence independently predicted sudden cardiac death/major ventricular arrhythmia (hazard ratio, 2.391 [95% CI, 1.046-5.464]; P=0.039).
CONCLUSIONS: LMNA missense variants localizing to IgD present a distinct apical pseudo-infarct LGE pattern associated with increased risk of ventricular arrhythmias and thromboembolic events but reduced atrioventricular block and atrial fibrillation. Multicenter studies are warranted to develop variant-specific risk-stratification strategies in cardiac laminopathy.