Disease progression rate is a strong predictor of ventricular arrhythmias in patients with cardiac laminopathies: a primary prevention cohort study

Christine Rootwelt-Norberg; Eystein T Skjølsvik; Monica Chivulescu; Martin P Bogsrud; Margareth P Ribe; Eivind W Aabel; Jan Otto Beitnes; Pål H Brekke; Trine F Håland; Nina E Hasselberg; Øyvind H Lie; Kristina H Haugaa

doi:10.1093/europace/euac192

Disease progression rate is a strong predictor of ventricular arrhythmias in patients with cardiac laminopathies: a primary prevention cohort study

Europace. 2023 Feb 16;25(2):634-642. doi: 10.1093/europace/euac192.

Authors

Christine Rootwelt-Norberg^{1

2}, Eystein T Skjølsvik^{1

2}, Monica Chivulescu^{1

2}, Martin P Bogsrud³, Margareth P Ribe^{1

2}, Eivind W Aabel^{1

2}, Jan Otto Beitnes^{1

2}, Pål H Brekke^{1

2}, Trine F Håland^{1

2}, Nina E Hasselberg^{1

2}, Øyvind H Lie^{1

2}, Kristina H Haugaa^{1

2

4}

Affiliations

¹ ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, PO Box 4950 Nydalen, 0424 Oslo, Norway.
² Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Unit for Cardiac and Cardiovascular Genetics, Oslo University Hospital, Ullevål, Norway.
⁴ Faculty of Medicine, Karolinska Institute and Cardiovascular Division, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Aims: Cardiac disease progression prior to first ventricular arrhythmia (VA) in LMNA genotype-positive patients is not described.

Methods and results: We performed a primary prevention cohort study, including consecutive LMNA genotype-positive patients from our centre. Patients underwent repeated clinical, electrocardiographic, and echocardiographic examinations. Electrocardiographic and echocardiographic disease progression as a predictor of first-time VA was evaluated by generalized estimation equation analyses. Threshold values at transition to an arrhythmic phenotype were assessed by threshold regression analyses. We included 94 LMNA genotype-positive patients without previous VA (age 38 ± 15 years, 32% probands, 53% females). Nineteen (20%) patients experienced VA during 4.6 (interquartile range 2.1-7.3) years follow up, at mean age 50 ± 11 years. We analysed 536 echocardiographic and 261 electrocardiogram examinations. Individual patient disease progression was associated with VA [left ventricular ejection fraction (LVEF) odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2-1.6 per 5% reduction, left ventricular end-diastolic volume index (LVEDVi) OR 1.2 (95% CI 1.1-1.3) per 5 mL/m2 increase, PR interval OR 1.2 (95% CI 1.1-1.4) per 10 ms increase]. Threshold values for transition to an arrhythmic phenotype were LVEF 44%, LVEDVi 77 mL/m2, and PR interval 280 ms.

Conclusions: Incidence of first-time VA was 20% during 4.6 years follow up in LMNA genotype-positive patients. Individual patient disease progression by ECG and echocardiography were strong predictors of VA, indicating that disease progression rate may have additional value to absolute measurements when considering primary preventive ICD. Threshold values of LVEF <44%, LVEDVi >77 mL/m2, and PR interval >280 ms indicated transition to a more arrhythmogenic phenotype.

Keywords: LMNA cardiomyopathy; Lamin A/C; Laminopathy; Primary preventive implantable cardioverter defibrillator; Ventricular arrhythmia.

MeSH terms

Arrhythmias, Cardiac / diagnosis
Arrhythmias, Cardiac / genetics
Cohort Studies
Defibrillators, Implantable* / adverse effects
Disease Progression
Female
Humans
Laminopathies* / complications
Male
Primary Prevention
Risk Factors
Stroke Volume
Ventricular Function, Left

Abstract

MeSH terms

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