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ICD placement

The clinical case of the month: June 2008

A 36-year-old man was diagnosed because of syncope with episodes of supraventricular tachycardia of up to 200 bpm, treated with cardioversion. Echocardiographic study revealed LV dilation (%LVE 126) and reduced LVEF – 40%. Coronary angiography was normal.
Myocardial Disease

Endomyocardial biopsy was taken, H+E examination revealed non-specific findings. Electrophysiologic study excluded the presence of accessory pathways. Following mild doses of beta-blocker treatment, conduction disease was unmasked showing bradycardia and second degree a-v block (Wenckebach type) and episodes of atrial fibrillation with slow ventricular response. The patient received DDD pacemaker. Within 4 years the patient developed progressive decrease of exercise tolerance, signs of heart failure; his LVEF dropped to <20%. Following poor response to full conventional medical therapy, the patient received heart transplant.

Do you have any suggestion of inherited disease in this patient?

Following HTX, the patient came asking for genetic studies for his family, especially for his offspring. Cardiac examination including ecg and echocardiography showed no significant abnormality. A nonsense mutation Y481Stop was found in the LMNA in the proband and in three of his children. Following the genetic diagnosis, Holter 24h ecg monitoring was performed in all mutation carriers. The examination revealed two VE triplets in an 18-year-old girl, episodes of advanced II degree a-v block in a13- year-old girl and nsVT (a burst of 10 VE beats) in an 11-year-old boy. All three children were asymptomatic, feeling healthy.

Would you refer all three mutation carriers for ICD placement?

Pedigree of the family

Case of the month: ESC Working Group on Myocardial & Pericardial disease


Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment [1]. With the new European classification, we are prompted to think about familial vs nonfamilial disease; in this particular family the familial background is unlikely, the proband’s father died of heart attack at the age of 68 years and his mother is treated because of hypertension.

The course of the disease in the proband is typical of laminopathy. First symptoms: episodes of supraventricular arrhythmia, associated with a-v block were followed by steadily decreasing LV contractility, requiring heart transplantation [2, 3]. Mildly dilated left ventricle with severely depressed LV contractility, representing mildly dilated congestive cardiomyopathy, not present in the proband, is also a common presentation of laminopathy. Subclinical skeletal muscle involvement with elevated sCPK level may be present. DCM patients with laminopathy have poor prognosis. Heart involvement may belong to the spectrum of overlapping laminopathies characterized by the coexistence of several tissue involvements such as striated muscles with partial lipodystrophy [4, 5] and striated muscle with peripheral nerves and leuconychia [6]. Besides, other isolated cardiac conditions, such as apical left ventricular aneurysm without atrio-ventricular block [7], early atrial fibrillation [8] and left ventricular noncompaction are also linked to LMNA gene mutations [9].

A second question is much more difficult to answer. Accumulating evidence shows that LMNA mutation carriers are at increased risk of sudden death despite pacemaker implantation [10, 11]. Consequently, all mutation carriers should be considered as candidates for ICD implantation. The decision, however, is very difficult to make in teenagers, especially feeling healthy. The risk of death increases with age, little is known, however, about sudden death at young age in this subgroup. In this family, the eldest mutation carrier, following second Holter monitoring (showing 2 VE triplets and several episodes of sinus pauses during daily activities) received ICD. The mutation carrier with episodes of advanced II degree a-v block received a DDD pacemaker, and is considered for replacement with ICD. The youngest boy remains asymptomatic, receives a small dose of beta-blocker and undergoes regular follow-up with Holter ecg monitoring.


1. Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2008; 29: 270-276.
2. Taylor MR, Fain PR, Sinagra G, et al. Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. J Am Coll Cardiol 2003; 41: 771-780.
3. Arbustini E, Pilotto A, Repetto A, et al. Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease. J Am Coll Cardiol 2002; 39: 981-990.
4. van der Kooi AJ, Bonne G, Eymard B, et al. Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy. Neurology 2002; 59: 620-623.
5. Vantyghem MC, Pigny P, Maurage CA, et al. Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities. J Clin Endocrinol Metab 2004; 89: 5337-5346.
6. Goizet C, Yaou RB, Demay L, et al. A new mutation of the lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease, and leuconychia. J Med Genet 2004; 41: e29.
7. Forissier JE, Bonne G, Bouchier C, et al. Apical left ventricular aneurysm without atrio-ventricular block due to a lamin A/C gene mutation. Arch Mal Coeur Vaiss 2005; 98: 67-70.
8. Sebillon P, Bouchier C, Bidot LD, et al. Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations. J Med Genet 2003; 40: 560-567.
9. Hermida-Prieto M, Monserrat L, Castro-Beiras A, et al. Familial dilated cardiomyopathy and isolated left ventricular noncompaction associated with lamin A/C gene mutations. Am J Cardiol 2004; 94: 50-54.
10. Meune C, Van Berlo JH, Anselme F, Bonne G, Pinto YM, Duboc D. Primary prevention of sudden death in patients with lamin A/C gene mutations. N Engl J Med 2006; 354: 209-210.
11. van Berlo JH, de Voogt WG, van der Kooi AJ, et al. Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death? J Mol Med 2005; 83: 79-83.

Notes to editor

Zofia BilinskaBy Dr Zofia Bilinska. 1st Dept. Coronary Artery Disease and Outpatient Clinic, Institute of Cardiology, Warsaw, Poland

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.