Long-Term Outcome and Risk Stratification in Dilated Cardiolaminopathies

Pasotti, Michele; Klersy, Catherine; Pilotto, Andrea; Marziliano, Nicola; Rapezzi, Claudio; Serio, Alessandra; Mannarino, Savina; Gambarin, Fabiana Isabella; Favalli, Valentina; Grasso, Maurizia; Agozzino, Manuela; Campana, Carlo; Gavazzi, Antonello; Febo, Oreste; Marini, Massimiliano; Landolina, Maurizio; Mortara, Andrea; Piccolo, G.; Viganò, Mario; Tavazzi, Luigi; Arbustini, Eloisa

doi:10.1016/j.jacc.2008.06.044

Cited by 340 publications

(283 citation statements)

References 28 publications

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“…Phenotypic penetrance is age-related but the expression is extremely heterogeneous, so that muscular and arrhythmic disease can be present in combination in the same patient, or one phenotypic manifestation can appear earlier than the other or even not become overt for a long time [6]. Moreover, both the severity of the disease and its progression may have a marked interindividual variability also within the same family of affected patients.…”

Section: Laminopathies and The Heartmentioning

confidence: 99%

“…The systolic function, as measured by left ventricular ejection fraction, has to be measured (values below 50% characterize systolic dysfunction) and monitored over time in order to assess disease progression. The expression of the pattern of dilated cardiomyopathy was found to be age-dependent, with development of the phenotype between 20 and 39 years in two thirds of the cases and complete penetrance by 60 years [6]. …”

Section: Dilated Cardiomyopathymentioning

confidence: 99%

“…Usually, the expression of a pattern of dilated cardiomyopathy follows that of the arrhythmic manifestations, or the two manifestations can be associated at the time of the first diagnosis [6]. Dilated cardiomyopathy related to laminopathies can present an aggressive and rapid evolution to very severe and potentially life-threatening conditions, with a worse natural history in comparison with other forms of non-ischemic dilated cardiomyopathy [6,21]. In these cases of progressive and worsening heart failure, other options in addition to pharmacological treatment can be considered.…”

Section: Dilated Cardiomyopathymentioning

confidence: 99%

“…In an observational study of 94 patients with dilated cardiomyopathy due to lamin A/C mutations, the outcome in years was predicted at multivariable analysis by a series of variables, with New York Heart Association functional class III to IV and history of highly dynamic competitive sports for ≥10 years being independent predictors of total events (arrhythmias, heart failure, death) and splice site mutations and competitive sport being associated with increased risk of sudden cardiac death [6]. …”

Section: Dilated Cardiomyopathymentioning

confidence: 99%

“…A detailed review of all the literature published on the risk of ventricular tachyarrhythmias, and on device activations in carriers of an implantable cardioverter defibrillators (ICDs) are shown in Table 2, in relationship to the series of patients with laminopathies reported in Table 1 [4,6,23,24,27,43,44,47,51–62]. In the largest observational study, reported by Kumar et al [24], the cumulative occurrence of sustained ventricular tachyarrhythmias was 34% at 7 years, and among patients with no history of ventricular tachyarrhythmias the incidence was 22% during a 7-year follow-up.…”

Section: Ventricular Tachyarrhythmias and Sudden Cardiac Deathmentioning

confidence: 99%

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Cardiolaminopathies from bench to bedside: challenges in clinical decision-making with focus on arrhythmia-related outcomes

Boriani

Biagini

Ziacchi

et al. 2018

Nucleus

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Lamin A/C gene mutations can be associated with cardiac diseases, usually referred to as ‘cardiolaminopathies’ characterized by arrhythmic disorders and/or left ventricular or biventricular dysfunction up to an overt picture of heart failure. The phenotypic cardiac manifestations of laminopathies are frequently mixed in complex clinical patterns and specifically may include bradyarrhythmias (sinus node disease or atrioventricular blocks), atrial arrhythmias (atrial fibrillation, atrial flutter, atrial standstill), ventricular tachyarrhythmias and heart failure of variable degrees of severity. Family history, physical examination, laboratory findings (specifically serum creatine phosphokinase values) and ECG findings are often important ‘red flags’ in diagnosing a ‘cardiolaminopathy’. Sudden arrhythmic death, thromboembolic events or stroke and severe heart failure requiring heart transplantation are the most dramatic complications of the evolution of cardiolaminopathies and appropriate risk stratification is clinically needed combined with clinical follow-up. Treatment with cardiac electrical implantable devices is indicated in case of bradyarrhythmias (implant of a device with pacemaker functions), risk of life-threatening ventricular tachyarrhythmias (implant of an ICD) or in case of heart failure with wide QRS interval (implant of a device for cardiac resynchronization). New technologies introduced in the last 5 years can help physicians to reduce device-related complications, thanks to the extension of device longevity and availability of leadless pacemakers or defibrillators, to be implanted in appropriately selected patients. An improved knowledge of the complex pathophysiological pathways involved in cardiolaminopathies and in the determinants of their progression to more severe forms will help to improve clinical management and to better target pharmacological and non-pharmacological treatments.

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Section: Laminopathies and The Heartmentioning

confidence: 99%

Section: Dilated Cardiomyopathymentioning

confidence: 99%

Section: Dilated Cardiomyopathymentioning

confidence: 99%

Section: Dilated Cardiomyopathymentioning

confidence: 99%

Section: Ventricular Tachyarrhythmias and Sudden Cardiac Deathmentioning

confidence: 99%

See 3 more Smart Citations

Cardiolaminopathies from bench to bedside: challenges in clinical decision-making with focus on arrhythmia-related outcomes

Boriani

Biagini

Ziacchi

et al. 2018

Nucleus

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Mortality Among Patients With Early-Onset Atrial Fibrillation and Rare Variants in Cardiomyopathy and Arrhythmia Genes

Yoneda

Anderson

et al. 2022

JAMA Cardiol

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IMPORTANCE Patients with early-onset atrial fibrillation (AF) are enriched for rare variants in cardiomyopathy and arrhythmia genes. The clinical significance of these rare variants in patients with early-onset AF is unknown.OBJECTIVE To assess the association between rare variants in cardiomyopathy and arrhythmia genes detected in patients with early-onset AF and time to death. DESIGN, SETTING, AND PARTICIPANTSThis prospective cohort study included participants with AF diagnosed before 66 years of age who underwent whole-genome sequencing through the National Heart, Lung and Blood Institute's Trans-Omics for Precision Medicine program.

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Genetics of Human Laminopathies

Novelli

D’Apice

2017

Encyclopedia of Life Sciences

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Lamins A/C, encoded by LMNA gene, are constituents of the nuclear lamina, a meshwork of proteins underneath the nuclear envelope. Human disorders linked to LMNA mutations are known as laminopathies and include cardiac and muscular dystrophies, lipodystrophies, progeroid syndromes and overlapping phenotypes. Associated with this wide clinical variability, there is also a large allelic heterogeneity that is still expanding. New links between LMNA mutations and human diseases with already known or unknown molecular cause have been established. In other cases, no evidence that a human disease is another laminopathy has been found. Moreover, the recent availability of high‐throughput sequencing technologies has made feasible to uncover the disease‐causing mutations in patients who were originally diagnosed with laminopathies but whose mutational analysis of candidate gene did not reveal any change in LMNA . Key Concepts Mutations in the LMNA gene, encoding A‐type lamin proteins, lead to a wide range of diseases known as laminopathies. The clinical and allelic heterogeneity of laminopathies is still expanding. Studies of the molecular mechanisms underlying laminopathies have led to advances in the understanding of lamin A functions and developing novel therapeutic strategies. A group of progeroid phenotypes is phenocopy of progeroid laminopathies. High‐throughput sequencing technologies have made it possible to uncover the disease‐causing mutations in genes that encode proteins involved in nuclear envelope architecture or in control of genomic stability. Nuclear alterations are linked to human ageing.

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Long-Term Outcome and Risk Stratification in Dilated Cardiolaminopathies

Cited by 340 publications

References 28 publications

Cardiolaminopathies from bench to bedside: challenges in clinical decision-making with focus on arrhythmia-related outcomes

Cardiolaminopathies from bench to bedside: challenges in clinical decision-making with focus on arrhythmia-related outcomes

Mortality Among Patients With Early-Onset Atrial Fibrillation and Rare Variants in Cardiomyopathy and Arrhythmia Genes

Genetics of Human Laminopathies

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