Relation between QT duration and maximal wall thickness in familial hypertrophic cardiomyopathy.

BACKGROUND: QT abnormalities have been reported in left ventricular hypertrophy and hypertrophic cardiomyopathy. OBJECTIVE: To determine the relation between left ventricular hypertrophy and increased QT interval in familial hypertrophic cardiomyopathy. METHODS: The QT interval was measured in 206 genotyped adult subjects with familial hypertrophic cardiomyopathy from 15 unrelated families carrying mutations in the beta myosin heavy chain (beta-MHC) gene (five families, n = 68) or the cardiac myosin binding protein C (MyBPC) gene (10 families, n = 138). Subjects were classified as genetically unaffected (controls, n = 112), affected with left ventricular hypertrophy (penetrants, n = 58), or affected without left ventricular hypertrophy (non-penetrants, n = 36). RESULTS: There was a significant increase in QTmax and QTmin from controls to non-penetrants and penetrants for both the MyBPC group (p < or = 0.001 and p < or = 0.001, respectively) and the beta-MHC group (p < or = 0.001 and p < or = 0.001, respectively). In the MyBPC group, the increase in the QT interval could be explained by increased left ventricular hypertrophy. In the beta-MHC group, non-penetrants had a significantly longer QTmax than controls despite the absence of left ventricular hypertrophy, and a similar QT interval to penetrants despite a lesser degree of left ventricular hypertrophy. CONCLUSIONS: In familial hypertrophic cardiomyopathy, genetically affected subjects without left ventricular hypertrophy may have a prolonged QT duration, which depends not only on the degree of left ventricular hypertrophy, when present, but also on the causative mutation.

[Familial hypertrophic cardiomyopathy. French study of the duration and outcome of pregnancy]. / Cardiomyopathie hypertrophique familiale. Etude française du déroulement des grossesses et des accouchements.

Hypertrophic cardiomyopathy (HCM) is a rare, often familial condition, which may be complicated by syncope, atrial or ventricular arrhythmias and episodes of cardiac failure. This genetic disease affects young people and may be observed in women wishing for a pregnancy. The duration and outcome of such pregnancies has not been extensively studied. The authors undertook a retrospective study by questionnaire to compare the pregnancies of 41 women with HCM, a total of 150 pregnancies, with those of 39 unaffected women from the same families: a total of 132 pregnancies. None of the women died, there were no hospital admission for cardiac causes and there was no aggravation of functional status (31% of women with HCM had symptoms before pregnancy compared with 27% during pregnancy). The foetal prognosis was good with no increase in prematurity or neonatal crises. Only the women with symptoms before pregnancy had an increased risk of foetal prematurity compared with healthy women (18% versus 5%). These results indicate the good tolerance of pregnancy of women with HCM and should lead to a revision of systematic medical contra-indication of pregnancy in these patients.

[Hypertrophic cardiomyopathy. Long-term clinical development in a regional cohort of 243 patients]. / Cardiomyopathie hypertrophique. Evolution clinique à long terme d'une cohorte régionale de 243 patients.

This retrospective study was undertaken to assess the long-term clinical outcome of hypertrophic cardiomyopathy (HCM) in a regional cohort of 243 patients aged 40.4 years on average at the time of diagnosis and followed up for 12.3 +/- 8.1 years. Forty-one deaths were recorded during the follow-up period directly related to HCM (including 20 sudden deaths and 17 deaths due to cardiac failure), an annual cardiac mortality rate of 1.37%. In multivariate analysis, two factors were associated with extra mortality: occurrence of the first symptoms before the age of 20 (RR x 2.35) (p = 0.006) and NYHA functional classes III: IV at the latest clinical assessment (p = 0.005). The risk of sudden death increased significantly with septal wall thickness: RR x 2.34 (p = 0.05), RR x 3.27 (p = 0.007) and RR x 3.67 (p = 0.02) respectively, for septal thickness equal to or greater than 25, 30 and 35 mm. Eighty-three patients (34%) had major cardiovascular events (sudden death, congestive cardiac failure, cerebrovascular accident) during follow-up. However, at the latest clinical assessment, 79% were relatively unaffected by their disease, without treatment (12%) or with drug therapy alone (60%). In a minority of patients (28%) a more aggressive therapeutic approach was necessary: cardiac pacing (N = 48), implantable cardiac defibrillators (N = 2) myomectomy (N = 27) or cardiac transplantation (N = 6). The authors conclude that HCM is a complex disease, less serious than initially thought in the majority of patients, but the cause of major cardiovascular events and premature deaths which still remain difficult to prevent.

[Can one die of sorrow?]. / Peut-on mourir de chagrin?

The authors report the case of a 49 year old woman who, on two occasions four years apart, presented with cardiogenic shock following the same type of intense emotional stress. Acute left ventricular systolic dysfunction in the initial phase regressed completely with drugs. A diagnostic investigation excluded atheromatous coronary artery disease, myocarditis and pheochromocytoma. Two hypotheses remained: prolonged coronary spasm causing myocardial stunning or acute catecholaminergic cardiomyopathy secondary to the stress.

Clinical features and prognostic implications of familial hypertrophic cardiomyopathy related to the cardiac myosin-binding protein C gene.

BACKGROUND: Little information is available on phenotype-genotype correlations in familial hypertrophic cardiomyopathy that are related to the cardiac myosin binding protein C (MYBPC3) gene. The aim of this study was to perform this type of analysis. METHODS AND RESULTS: We studied 76 genetically affected subjects from nine families with seven recently identified mutations (SASint20, SDSint7, SDSint23, branch point int23, Glu542Gln, a deletion in exon 25, and a duplication/deletion in exon 33) in the MYBPC3 gene. Detailed clinical, ECG, and echocardiographic parameters were analyzed. An intergene analysis was performed by comparing the MYBPC3 group to seven mutations in the beta-myosin heavy-chain gene (beta-MHC) group (n=52). There was no significant phenotypic difference among the different mutations in the MYBPC3 gene. However, in the MYBPC3 group compared with the beta-MHC group, (1) prognosis was significantly better (P<0.0001), and no deaths occurred before the age of 40 years; (2) the age at onset of symptoms was delayed (41+/-19 versus 35+/-17 years, P<0.002); and (3) before 30 years of age, the phenotype was particularly mild because penetrance was low (41% versus 62%), maximal wall thicknesses lower (12+/-4 versus 16+/-7 mm, P<0.03), and abnormal T waves less frequent (9% versus 45%, P<0.02). CONCLUSIONS: These results are consistent with specific clinical features related to the MYBPC3 gene: onset of the disease appears delayed and the prognosis is better than that associated with the beta-MHC gene. These findings could be particularly important for the purpose of clinical management and genetic counseling in familial hypertrophic cardiomyopathy.

[Restrictive cardiomyopathy]. / Cardiomyopathies restrictives.

Restrictive cardiomyopathies are the rarest forms of cardiomyopathy. They are characterised by restrictive filling and reduction in diastolic volume of one or both ventricles with normal wall thickness and systolic function. Increased interstitial fibrosis may be observed. This form of cardiomyopathy may be idiopathic or associated with other conditions (amyloid disease, endomyocardial pathology with or without hypereosinophilia). The idiopathic variety is sometimes familial. The symptoms are not specific except for angina in cases of amylosis. All the signs of cardiac failure except cardiomegaly are present in advanced stages. In the idiopathic forms, thromboembolic complications are common. Atrial fibrillation and atrioventricular block are also often observed. The differential diagnosis with chronic constrictive pericarditis is sometimes difficult. Different investigations (Doppler echocardiography, CT scan, magnetic resonance imaging, isotopes, cardiac catheterisation and endomyocardial biopsy) may all fail to make the diagnosis and pericardectomy may have to be performed in the last resort. Treatment is based on diuretics, prevention of atrial fibrillation (amiodarone) and oral anticoagulants. Digoxin, which fixes to amyloid fibrils, may be arrhythmogenic in amyloidosis. Cardiac pacing may be used in cases of atrioventricular block and brady-arrhythmias. Cardiac transplantation is available in advanced forms after exclusion of amyloidosis. New specific therapeutic approaches to amyloidosis are discussed.

Spontaneous dissection of the celiac artery.

We describe a case of intestinal angina caused by spontaneous dissection of the celiac artery and thrombosis of the superior mesenteric artery. Spontaneous dissection of a visceral artery is an uncommon occurrence that is usually diagnosed after fatal hemorrhage or ischemia. The underlying mechanism is unclear but the frequent association with multiple arterial lesions suggests general arterial disease. In symptomatic forms, surgical reconstruction is mandatory, to treat the lesion and allow definitive histological diagnosis.

[Left ventricular systolic dysfunction in cardiomyopathies]. / Dysfonction ventriculaire systolique dans les myocardiopathies.

Of the three physiopathological types of cardiomyopathy, dilated, hypertrophic and restrictive, it is the first which characteristically shows major left ventricular systolic dysfunction. The left ventricular volumes are increased, the ventricle becomes spherical and global ejection fraction decreases with diffuse or segmental wall motion abnormalities. The left ventricular mass is increased in an excentrical fashion with wall thinning. Isovolumic contraction is slower, the ejection time is shorter and, above all, the indices of contractility such as maximal velocity of the contractile elements ... are very abnormal and do not improve after positive inotropic stimulation.

[Cardiac pacing and cardiac insufficiency]. / Stimulation cardiaque et insuffisance cardiaque.

Permanent Dual-chamber cardiac pacing has been proposed as treatment of advanced cardiac failure due to ischaemic or primary dilated, hypokinetic cardiomyopathies, since 1986. After encouraging initial results in 1990, the most recent studies have reported less convincing results, justifying the need for prospective, randomised studies. The physiopathological mechanisms underlying the haemodynamic improvement remain unknown.

[Virus and dilated cardiomyopathies]. / Virus et cardiomyopathies dilatées.

Dilated cardiomyopathy is so called when an etiological investigation is negative and no cause can be found for ventricular dilatation-hypokinesia. Current research points to genetic, immunological and infectious factors, often associated, and the passage of subclinical viral myocarditis to chronic disease. There is a lot of evidence in favour of this hypothesis. In the experimental model, the relationship between viral myocarditis and dilated cardiomyopathy has been demonstrated with, as cofactors, a genetic predisposition and an immunitary deficiency leading to an auto-immune subacute myocarditis. In the clinical setting, the enterovirus with a high cardiac tropism seems to play an epidemiological role in the genesis of dilated cardiomyopathy. The concentrations of neutralising anti-coxsackie B virus antibodies is higher in subjects with dilated cardiomyopathy than in a control population. The frequency of lymphocytic infiltration, a marker of dysimmunitary myocarditis, is variable from study to study but the presence of sequences of enterovirus genome in the myocardium could explain slow replication of the virus progressively destroying the myocytes. Techniques of molecular hybridization with or without prior genic amplification by the "Polymerase Chain Reaction" have demonstrated such sequences of specific enterovirus genome but discordant results require further studies.

[Right atrioventricular metastasis of myxoid liposarcoma. Prolonged course after repeated surgery and chemotherapy]. / Métastase auriculo-ventriculaire droite d'un liposarcome myxoïde. Evolution prolongée avec chirurgie itérative et chimiothérapie.

The authors report a case of cardiac metastasis of a myxoid liposarcoma of the thigh in a 54 year old woman. The treatment associated repeated surgical ablation and chemotherapy. The drugs used induced some cardiotoxicity which limited their prescription but nevertheless, the patient survived 5 years. Previous reported cases do not describe survival lasting more than 2 years and associated chemotherapy would therefore seem to be a valuable adjuvant, increasing the life expectancy of such patients.

Detection of enteroviruses in endomyocardial biopsy by molecular approach.

Enteroviruses are considered to be the most common agents implicated in myocarditis and cardiomyopathy. Recent studies have suggested persistent enterovirus infection in chronic disease showing the presence of enteroviral RNA in the myocardium. We used gene amplification by PCR which can demonstrate directly the presence of enteroviral sequences in endomyocardial biopsies. The primers were chosen in the 5' non-coding region of the genome representing highly conserved sequences among enteroviruses and therefore allowed the amplification of the majority of enteroviruses. The hybridization of the amplified products was effected with specific general riboprobe derived from 5' non-coding sequences internal of the amplified fragments. The results include 105 patients distributed in 6 groups: 45 idiopathic dilated cardiomyopathies with 66.7%, 17 alcoholic cardiomyopathies with 52.9%, 10 myocarditis with 30%, 5 multifactorial cardiomyopathies with 40%, 5 patients with immunosuppressive therapy with 100%, and 23 control group without viral etiology with 39.1% positive samples. The study suggested a positive link between viral infection and cardiomyopathies, but did not allow a direct relation between enterovirus infection and idiopathic dilated cardiomyopathy to be established.