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Biomedical subjects

M Komajda

Publications and source records attributed to M Komajda.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Silent Q fever endocarditis. Report of a case].

A murmur of aortic regurgitation was discovered in an asymptomatic patient who had suffered from an acute Coxiella Burnetti infection several months before hand. Transoesophageal echocardiography, serology and direct immunofluorescence of the aortic valve confirmed the diagnosis of Q fever endocarditis. Treatment with Vibramycin and Plaquenil was instituted after aortic valve replacement. Cardiac complications of Q fever should be recognised as they may remain asymptomatic for long periods of time. Transthoracic and transoesophageal echocardiography should be widely used in acute forms of Q fever and systematic in chronic infections with Coxiella Burnetti.

Adult↗
PubMed1999

[Evaluation of a specific French scale of activity in chronic heart failure. A national multicenter study. Group for Cardiac Insufficiency and Cardiomyopathy of the French Society of Cardiology].

Many systems have been proposed to evaluate the functional incapacity caused by chronic cardiac failure. The classification of the New York Heart Association (NYHA) is the best known. It is subjective, poorly reproducible and has a poor predictive value on effort. The authors propose a Specific French Scale of Activity with the object of a more accurate functional evaluation of cardiac failure, easier to use by the doctor and more specific to French patients and their life styles. A French multicentre study was set up in hospital departments by the French Society of Cardiology working group on Cardiomyopathy and Cardiac Failure to assess this new classification with respect to the NYHA classification and peak VO2 (Weber's classification). Eight centres participated in the study. A total of 124 patients with chronic cardiac failure and a mean age of 61 years (102 men) were included. Cardiac failure was due to ischaemic heart disease in 72 cases, hypertension in 10 cases, dilated cardiomyopathy in 40 cases and aortic regurgitation in 2 cases. Eighty-two patients underwent a double evaluation using the French Scale: 40 patients by 2 physicians and 42 patients by a physician and a nurse. Good reproducibility was found between the assessment by the 2 physicians in 35 cases (87%) and between the physician and nurse in 30 cases (71%). When compared with peak VO2, the classification was concordant in 47% of cases using the NYHA and in 61% of cases using the French Scale, with variation of one class in 40% of cases with the NYHA and 35% of cases with the French Scale. These results show good reproducibility and correspondence of classification with the exercise test which was better using the French Scale than the NYHA classification.

Aged↗
PubMed1998

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.

Adolescent↗
PubMed1998

Genotype-phenotype analysis in four families with mutations in beta-myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy is a genetically heterogeneous disease in which one of the most frequently implicated gene is the gene encoding the beta-myosin heavy chain. To date, more than 40 distinct mutations have been found within this gene. In order to progress on the determination of genotype-phenotype relationship, we have screened the beta-myosin heavy chain gene for mutations in 18 probands from unrelated families. We identified the mutation implicated in the disease in four families. Two of them, the Glu930 codon deletion and the Ile263Thr mutation, are reported here for the first time. The two other mutations are the Arg723Cys mutation, that was previously described in a proband as a de novo mutation, and the Arg719Trp mutation. A poor prognosis was associated with the Glu930codon deletion (mean maximal wall thickness (MWT) = 19.5 mm +/- 5) and the Arg719Trp mutation (mean MWT = 15.3 mm +/- 7), whereas a good prognosis was associated with the Arg723Cys mutation (mean MWT = 20.1 mm +/- 7). The combination of clinical and genetic characteristics of each family member suggests that prognosis is related neither to the degree of left ventricular wall thickness nor to a change in the net electrical charge of the protein. Additional family studies are needed to confirm these findings and to contribute to stratify the prognosis according to the mutation involved.

Adolescent↗
PubMed1998

Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy.

Five disease genes encoding sarcomeric proteins and associated with familial and classical forms of hypertrophic cardiomyopathy have been determined since 1989. In 1996 two other genes encoding ventricular regulatory and essential myosin light chains were shown to be associated with a particular phenotype of the disease characterized by mid left ventricular obstruction. The aim of the present study was to search for mutations in the ventricular regulatory myosin light chain gene (MYL2), located on chromosome 12q23q24.3, in a panel of 42 probands presenting a classical phenotype of familial hypertrophic cardiomyopathy. Single-strand conformation polymorphism analysis was used to search for mutations in the coding segments of the MYL2 gene, and the abnormal products were sequenced. Two novel missense mutations, Phe18Leu in exon 2 and Arg58Gln in exon 4 were identified in three unrelated families. None of the affected patients had hypertrophy localized only at the level of the papillary muscle with mid left ventricular obstruction. By analysis of genetic recombinations, one of these mutations identified in a large family allowed us to refine the localization of the MYL2 gene on the genetic map, in an interval of 6 cM containing six informative microsatellite markers. In conclusion, we show that mutations in the MYL2 gene may be involved in familial and classical forms of hypertrophic cardiomyopathy, and we provide new tools for the genetic analysis of patients with familial hypertrophic cardiomyopathy.

Adolescent↗
PubMed1998

Genotype-phenotype correlations in familial hypertrophic cardiomyopathy. A comparison between mutations in the cardiac protein-C and the beta-myosin heavy chain genes.

BACKGROUND: The gene involved in familial hypertrophic cardiomyopathy on chromosome 11 was recently identified as the cardiac myosin binding protein-C (MyBP-C) gene. The phenotype of two families associated with mutation in this gene is described here and compared to that of five families with mutations in the beta-myosin heavy chain gene. METHODS AND RESULTS: In adults (n = 33) bearing a splice acceptor site mutation in the MyBP-C gene, penetrance of familial hypertrophic cardiomyopathy was incomplete (69%) and ventricular hypertrophy mild. Among 37 clinical, electrocardiographic and echocardiographic parameters analysed, the only difference with the beta-MHC group (n = 35) was a shorter acceleration time of systolic flow in the pulmonary artery (P < 0.05). Sensitivity and specificity of diagnostic criteria were similar for the two genes. Cumulative survival rate for the splice acceptor site mutation (90% at 50 years old) was mid-way between that observed with a malignant (Arg403Leu: 42%) and a benign mutation (Arg403Trp: 100%) in the beta myosin heavy chain gene (P = 0.002). CONCLUSIONS: The detailed phenotype associated with a mutation in the MyBP-C gene was no different from that associated with mutations in the beta myosin heavy chain gene, except for prognosis which appeared more benign. These preliminary results suggest that there is no locus-specific genotype-phenotype correlation for the two genes analysed.

Adult↗
PubMed1998

Familial hypertrophic cardiomyopathy. Cardiac ultrasonic abnormalities in genetically affected subjects without echocardiographic evidence of left ventricular hypertrophy.

AIMS: It is not known whether the apparent normality of echocardiographic examination results, in subjects bearing a mutation for hypertrophic cardiomyopathy but without ultrasonic left ventricular hypertrophy, is due to incomplete phenotypic expression, or inaccurate echocardiographic criteria. The aim of this study was to search for echocardiographic abnormalities in these patients. METHODS AND RESULTS: Echocardiography was performed in 100 subjects from two families with a mutation in the beta-MHC (720) or My-BPC (714) genes. We compared genetically affected subjects with an apparently normal left ventricle (thickness < 13 mm) (20 patients), and nonaffected first-degree relatives (61 normal subjects). (1) Patients had a thicker left ventricular wall (9.7 +/- 1.4 vs 8.9 +/- 1.4 mm, P = 0.03), a greater indexed mass (107 +/- 18 vs 97 +/- 17 g. m-2, P = 0.03), a larger left atrium (27 +/- 9 vs 23 +/- 10 mm3, P = 0.09) and lower wall stress (78 +/- 11 vs 89 +/- 15 10(3) dynes. cm-2, P = 0.002); these differences were highly significant after adjustment for height, age and systolic blood pressure either for wall thickness (P = 0.000003), mass (P = 0.005) or atrial volume (P = 0.001), and the ventricular systolic dimension appeared smaller (P = 0.01); (2) results remained significant (P < 0.01) when a lower cut-off value (< or = 11 mm) or only adults (> or = 18 years) were considered; (3) a subanalysis of Family 714 (13 patients, 25 normals matched for sex, age and height) showed the same trends. CONCLUSION: In familial hypertrophic cardiomyopathy, genetically affected subjects with an apparently normal heart by echocardiography show slight ultrasonic structural and functional left ventricular modifications, suggesting that the phenotype of the disease is a continuous spectrum from normal structure to typical hypertrophy.

Adolescent↗
PubMed1998

Diagnostic value of electrocardiography and echocardiography for familial hypertrophic cardiomyopathy in genotyped children.

AIM: The aim of the study was to evaluate electrocardiography and echocardiography in the diagnosis of familial hypertrophic cardiomyopathy in children, using the genetic status as the criterion of reference. METHODS AND RESULTS: We analysed 35 children (<18 years) from 13 families with identified mutations: 16 were genetically affected (11.2 +/- 3 years), 19 unaffected (13.1 +/- 2.8 years). Conventional major diagnostic criteria were: left ventricular wall thickness >95% confidence interval on the echocardiogram; abnormal Q waves, left ventricular hypertrophy (voltage >95th percentile), or marked ST-T changes on the electrocardiogram. Twenty-two minor electrocardiographic and echocardiographic criteria were also analysed. Using major criteria, the specificity of the electrocardiogram and echocardiogram was excellent (100% for both) but sensitivity was particularly low (38% and 50% respectively). However, when four relevant additional criteria (QRS axis, left atrium dimension, intraventricular septum/posterior wall ratio, E/A wave ratio) were taken into account, sensitivity increased to 88% and specificity remained high (95%). CONCLUSIONS: (1) Familial hypertrophic cardiomyopathy was diagnosed in only approximately 50% of genetically affected children by conventional electrocardiographic and/or echocardiographic criteria. (2) Relevant additional diagnostic criteria were selected so that nearly all children considered as healthy carriers of a mutation (based on conventional criteria) could be identified with excellent specificity.

Adolescent↗
PubMed1998

[Clinical application of the genetic aspects of familial hypertrophic cardiomyopathy].

Familial hypertrophic cardiomyopathy is a disease with very heterogeneous genetic characteristics, both at the intergenic level (7 genes have been identified and some of them are still unknown) and intragenic level (more than 100 mutations have been identified). This genetic heterogeneity at least partly explains the clinical heterogeneity, expressed in terms of the degree of left ventricular hypertrophy and the inherent risk related to the disease (sudden death and/or heart failure). However, the understanding of phenotype/genotype relationships of this disease is only in the very early stages. So-called "modifier" genes are probably involved to modify the clinical profile of the disease. Many healthy carriers have been identified, but their outcome is unknown at the present time. The molecular genetics of HCM allows reevaluation of the classical clinical criteria. In the future, it would be desirable to establish specialized units for predictive and antenatal diagnosis, composed of cardiologists specialized in the disease, geneticists and psychologists in order to consider all clinical, ethical, and psychological aspects of this disease. Hopefully, this new approach to cardiology will be able to establish a more accurate risk profile for exposed subjects and guide treatment options.

Cardiomyopathy, Hypertrophic↗
PubMed1997

Diagnostic value of electrocardiography and echocardiography for familial hypertrophic cardiomyopathy in a genotyped adult population.

BACKGROUND: The diagnostic value of ECG and echocardiography for familial hypertrophic cardiomyopathy (FHC) has not been reassessed since the development of molecular genetics. The aim of the study was to evaluate it in adults, with the genetic status used as the criterion of reference. METHODS AND RESULTS: Ten families with previously identified mutations were studied (9 mutations in 3 genes). ECG and echocardiography were analyzed in 155 adults, of whom 77 were genetically affected and 78 unaffected. The major diagnostic criteria were, for echocardiography, a left ventricular wall thickness > 13 mm and, for ECG, abnormal Q waves, left ventricular hypertrophy, and marked ST-T changes. Minor ECG and echographic abnormalities were also analyzed. (1) Sensitivity and specificity of major criteria were 61% and 97% for ECG and 62% and 100% for echocardiography. (2) Sensitivity but not specificity was age related (from 50% at < 30 years to 94% at > 50 years old, P < .01) and sex related (83% in men versus 57% in women, P = .01). (3) Sensitivity was improved by the addition of minor criteria and by the association of ECG and echocardiography. The negative predictive value was therefore very good (95%) at > 30 years of age. (4) Healthy carriers without any ECG or echocardiographic abnormality represented 17% of genetically affected adults. CONCLUSIONS: ECG and echocardiography have similar diagnostic values for FHC in adults, with an excellent specificity and a lower sensitivity. The association of the two techniques allows a better evaluation of the risk of being genetically affected in families with hypertrophic cardiomyopathy.

Adult↗
PubMed1997

Correlation between left ventricular hypertrophy and GAA trinucleotide repeat length in Friedreich's ataxia.

BACKGROUND: Friedreich's ataxia (FA), the most common inherited ataxia, is associated frequently with cardiac hypertrophy, and death is often cardiac related. Recently, the disease has been associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the gene encoding frataxin on chromosome 9. METHODS AND RESULTS: We studied 44 consecutive patients with FA, determined the size of GAA expansions in the frataxin gene, and examined the relation between the genotype and cardiac phenotype assessed by M-mode and two-dimensional echocardiography. All the patients were homozygous for the mutation. The size of the GAA expansion on the smaller allele varied from 270 to 1200. We found a correlation between the size of GAA expansion and the left ventricular wall thickness (r = .51, P < .001) and the left ventricular mass index (r = .45, P = .002). Left ventricular hypertrophy was observed in 81% of patients with a number of GAA repeats above the median value of 770 compared with only 14% in the other group (P = .002). CONCLUSIONS: These data demonstrate that in FA, the severity of left ventricular hypertrophy is related to the number of GAA repeats. These results suggest that abnormalities of the gene encoding frataxin, a protein of unknown function highly expressed in the normal heart, may play an important role in the modulation of cardiac hypertrophy.

Adult↗
PubMed1997

The influence of the angiotensin I converting enzyme genotype in familial hypertrophic cardiomyopathy varies with the disease gene mutation.

Familial hypertrophic cardiomyopathy is an autosomal dominant genetically heterogeneous disease characterized by a partial penetrance and variable expressivity. Previous studies showed that the extent of hypertrophy is influenced by the angiotensin I converting enzyme insertion/deletion (I/D) polymorphism. Recently, molecular genetic analysis revealed the existence of healthy carriers and that as many as a quarter of genetically affected individuals do not express the disease. This data prompted us to re-investigate the role of the angiotensin I converting enzyme polymorphism on hypertrophy by assessing both clinically affected individuals and healthy carriers. For this, several families with mutations in the cardiac myosin binding protein C or the beta-myosin heavy chain genes were analysed. The mean maximal intraventricular septum thickness was compared as a function of angiotensin I converting enzyme genotypes in all genetically affected individuals (n = 114), and in subsets of subjects carrying either a splice acceptor site mutation in the cardiac myosin binding protein C gene (n = 33), or various missense mutations in the cardiac beta-myosin heavy chain gene (n = 81) or finally, mutation in the Arg403 codon of the beta-myosin heavy chain gene (n = 54). Significant association between the D allele and hypertrophy was observed only in the case of Arg403 codon mutations (mean septum thickness for subjects with the DD genotype: 19.3 +/- 2.7 mm: with the ID genotype: 13.4 +/- 1.3 mm and with the II genotype: 11.0 +/- 0.9 mm; P < 0.02). These results were confirmed by the chi 2 test showing an over-representation of DD genotype in patients carrying an Arg403 codon mutation associated with septal hypertrophy (P < 0.05). Our data confirms that the angiotensin I converting enzyme genotypes can influence the phenotypic expression of hypertrophy and shows that this influence depends on the mutation, raising the concept of multiple genetic modifiers in familial hypertrophic cardiomyopathy.

Adult↗
PubMed1997

Prognostic value of plasma endothelin-1 in patients with chronic heart failure.

AIMS: Endothelin-1 is a potent vasoconstrictive and multifunctional peptide. Elevated concentrations have been reported in congestive heart failure. We hypothesized that the level of endothelin-1 in plasma is a prognostic marker in congestive heart failure. METHODS AND RESULTS: Plasma levels of endothelin-1 were measured by radioimmunoassay in 120 congestive heart failure patients with ischaemic or non-ischaemic cardiomyopathy (mean ejection fraction 28 +/- 11%, in New York Heart Association (NYHA) functional class I:21, class II 35, class III: 61, class IV: 3). During a median follow-up of 361 +/- 338 days, 14 cardiac deaths occurred. In the univariate Cox model, endothelin-1 was the most powerful prognostic marker among the variables tested (P = 0.0001). A multivariate model, including plasma atrial natriuretic peptide and noradrenaline, NYHA class, age, and echocardiographic left ventricular end-diastolic diameter index was highly predictive of mortality (P = 0.00008), but only endothelin-1 remained significantly associated with outcome (P = 0.02). Patients with plasma endothelin-1 > or = 5 pg. ml-1 had a higher mortality rate than those with endothelin-1 < 5 pg. ml-1 (21% vs 4%, P = 0.001). CONCLUSION: Our results suggest that elevated endothelin-1 plasma levels are associated with a poor prognosis and routine plasma endothelin-1 determination provides important prognostic information in mild to moderate heart failure.

Atrial Natriuretic Factor↗