Biomedical subjects

M Komajda

Publications and source records attributed to M Komajda.

At least 127 records · Page 7Linked to original sources

PubMed1992

Model-based determination of cut-off values for left ventricular hypertrophy from echocardiographic myocardial mass data.

1. The left ventricular myocardial mass is a measurement that is easy to obtain by echocardiography. It is currently used for the definition of left ventricular hypertrophy, but cut-off values are often critical, since they depend on covariates of left ventricular myocardial mass such as sex, age, body surface area, physical training, blood pressure, etc. As it is very difficult in any laboratory to obtain a sufficient number of normal subjects for the establishment of left ventricular myocardial mass experimental distributions, we propose a non-linear model for the calculation of echocardiographic left ventricular myocardial mass distribution in normal subjects, from personal and literature data. left ventricular myocardial mass probability density function was computed from the following two assumptions: the joint distribution of the internal and external left ventricular diameters is assumed to be bivariate normal, and the relation between left ventricular myocardial mass and ventricular diameters is given by the formula of Devereux & Reicheck (Devereux, R. B. & Reicheck, N. Circulation 1977; 55, 613-8). 2. The Gaussian assumption was tested by using skewness tests. The model was further developed for the myocardial mass index distribution. The calculated probability density functions were compared with experimental data and showed very good agreement. Furthermore, they were used to define cut-off values of left ventricular hypertrophy at selected false-positive ratios. Finally, since left ventricular myocardial mass may vary under normal conditions with co-variates, the model may provide co-variate-matched cut-off values for any, even small, series of non-diseased control subjects.

Adult↗

PubMed1992

Cardiomyopathy in Friedreich's ataxia: a Doppler-echocardiographic study.

Heart involvement is frequent in Friedreich's ataxia (FA), the most prevalent of the spino-cerebellar degenerative diseases, which is inherited with an autosomal recessive pattern. However, the pathophysiological link between cardiac and neurological disorders is not yet clearly established. We compared a group of 10 patients with FA to a control group (C) of 16 normal subjects, using Doppler-echocardiography. To see whether cardiac involvement was specific to FA, the data of patients with FA were also compared to those of patients with autosomal dominant olivo-ponto-cerebellar atrophia (OPCA), another spino-cerebellar degenerative disease. There was an increase in left ventricular mass index in FA (154 +/- 9 g.m-2 vs 99 +/- 7 g. m-2 in C, P < 0.001), systolic function was normal, the ejection fraction (EF) slope and E/A ratio were decreased (85 +/- 9 mm.s-1 vs 130 +/- 7 mm.s-1 in C, P < 0.001 and 1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.01, respectively), while the isovolumic relaxation period was increased (96 +/- 3 ms vs 92 +/- 2 ms in C, P < 0.01). Deceleration time and time-velocity integrals of A wave to total mitral flow were not modified. In OPCA only the E/A ratio was decreased (1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.05). These data show the presence of cardiomyopathy in FA with left ventricular hypertrophy and suggest the presence of diastolic function abnormalities. The cardiomyopathy seems specifically associated with FA and not to spino-cerebellar degenerative disease in general.

Adolescent↗

PubMed1992

Plasma calcitonin gene-related peptide decreases in chronic congestive heart failure.

To investigate the role of calcitonin gene-related peptide (CGRP) in cardiac failure, a sensitive and specific radioimmunoassay was developed to study plasma levels of CGRP in 37 normal subjects and 41 patients with heart failure (HF). The mean plasma levels of CGRP were 294.3 pg.ml-1 (SEM: 41.4) in normal subjects and 121.2 pg.ml-1 (SEM: 21.2) in HF patients. The significant decrease observed in HF patients suggests that CGRP is involved in the pathogenesis of heart failure via a direct effect or via modulation of sympathetic nervous activity.

Calcitonin Gene-Related Peptide↗

PubMed1992

[Non invasive evaluation of cardiovascular effects of nebivolol in patients with cardiac insufficiency].

The results of several studies, mostly without controls, have suggested that betablockers, administered at progressively increasing doses, may be beneficial in cardiac failure. Based on this hypothesis, betablockers with a peripheral vasodilator effect, such as Nebivolol, could be particularly valuable in this indication. A preliminary study of its tolerance, haemodynamic and neurohormonal effects was carried out with a noninvasive methodology in 12 patients with cardiac failure in sinus rhythm, 8 men and 4 women (average age 53 +/- 12 years), all of whom had Class III or IV symptoms according to the NYHA Classification. The protocol had 2 phases: the first was an open phase during which Nebivolol was administered at a dose of 1 mg/day for 48 hours then 2.5 mg/day for 72 h. In the second phase, the patients were randomly separated into 2 groups, one to receive placebo and the other 2.5 mg for one week then 5 mg of Nebivolol for the 5 remaining weeks. The heart rate decreased significantly from 70 +/- 3 to 63 +/- 4 beats/min (p < 0.01) with Nebivolol 1 mg/day without further slowing at the 2.5 mg dosage. During the randomised phase, the heart rate remained stable in the Nebivolol group but increased to its initial value in the group given placebo. No aggravation of symptoms was observed in the Nebivolol group. No significant changes in cardiac output, parameters of cardiac loading or contractility could be demonstrated after 6 weeks' treatment. During submaximal exercise testing, plasma concentrations of catecholamines and atrial natriuretic factor tended to be higher with Nebivolol than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1992

[Atrial natriuretic factor and cardiac insufficiency].

The atrial natriuretic factor (ANF) is a vasodilating and natriuretic peptide. In experimental and human cardiac failure, plasma ANF concentrations are increased. The ANF is a good marker of functional and haemodynamic severity and of the prognosis of cardiac failure. In this syndrome, messenger RNA of ANF is expressed not only in the atria but also in the ventricles which also secrete the peptide. Attenuation of the natriuretic response is observed in cardiac failure. It may be related to an abnormality situated after the receptor and second messenger, cyclic GMP and/or the reduction of renal perfusion pressure which occurs in cardiac failure. The therapeutic perspectives of ANF in cardiac failure are limited by the necessity of continuous intravenous or parenteral administration. Inhibitors of the enzyme degrading the peptide, neutral endopeptidase, are under evaluation in clinical trials which are at a preliminary stage for the moment.

Atrial Natriuretic Factor↗

PubMed1992

[Nitrate derivatives and cardiac insufficiency].

Nitrate derivatives are venous vasodilators which are effective in reducing the symptoms of pulmonary congestion. The beneficial action on exercise capacity was recently demonstrated in the Veterans II Study in association with Hydralazine and has also been suggested by other trials. The reduction in mortality from cardiac failure was demonstrated in the Veterans I Study in association with Hydralazine compared to conventional digitalo-diuretic therapy but seems less important than that obtained by angiotensin converting enzyme inhibitors. The phenomenon of tolerance seems to be related to the use of high doses in continuous therapy and may be countered by discontinuous use of the drug during the 24 hour period. Tolerance seems to be related to neuro-hormonal factors and perhaps to depletion of SH groups. Simultaneous use of nitrates and ACE inhibitors seems to be an interesting therapeutic concept.

Aged↗

PubMed1991

Effects of arginine vasopressin and extracellular osmolarity on atrial natriuretic peptide release by superfused rat atria.

This study investigated the characteristics of atrial natriuretic peptide (ANP) release from superfused sliced atria and ventricles of rats. Right atria spontaneously released more immunoreactive ANP (Ir-ANP: pg/min per mg tissue) (32 +/- 3) than did left atria (11 +/- 2) or right ventricles (1.5 +/- 0.5). Addition of 10(-9) to 10(-5) M of arginine vasopressin (AVP) to the superfusing fluid or increasing its osmolarity (290 to 490 mOsM) resulted in a significant increase of the Ir-ANP outflow from right atria. The effect of AVP was prevented by a specific V1 receptor antagonist, ([d(ch2)5Tyr(Me)]AVP). Superfusion with indomethacin (10(-5) M) did not alter spontaneous release but inhibited the peak levels of Ir-ANP induced by AVP (10(-5) M). Moreover, DDAVP, a specific V2 receptor agonist, did not induce Ir-ANP release. Ca(2+)-free medium alone or plus 1 mM EGTA induced a significant increase in basal Ir-ANP outflow. The Ir-ANP released chromatographed similarly to the standard alpha-rANP. These results suggest a specific stimulatory effect of AVP and osmolarity and a negative influence of extracellular Ca2+ on atrial spontaneous Ir-ANP release. It appears that the effect of AVP could be mediated by prostaglandin synthesis.

Animals↗

PubMed1991

Skeletal actin mRNA increases in the human heart during ontogenic development and is the major isoform of control and failing adult hearts.

Expression of the two sarcomeric actins, alpha-skeletal and alpha-cardiac, is regulated in the rodent heart in response to developmental, hormonal, and hemodynamic stimuli. Little is known in man, except that both isogenes were found to be coexpressed in three adult ventricles. In this report, we investigated the isoactin mRNA composition in ventricles from 21 control patients (4 fetal, 5 juvenile, 12 adult) and from 15 patients undergoing cardiac transplantation (5 idiopathic dilated cardiomyopathies, 5 ischemic myopathies with myocardial infarcts, 5 diverse etiologies) by two different and complementary techniques: RNA dot blot analysis with specific cDNA probes, and primer extensions with an oligonucleotide common to alpha-cardiac and alpha-skeletal actins. In the case of dot blot analysis, quantification of each isoform was performed by using as standards RNA transcripts obtained from cloned human alpha-actin sequences, and the total amount of sarcomeric actin mRNA was evaluated as a function of total poly(A+)RNA. We found that both isogenes are always coexpressed, and that the isoactin pattern changes during development. In utero and in neonatal hearts, alpha-skeletal actin mRNA represents less than or equal to 20% of sarcomeric actins, it increases to 48 +/- 6% during the first decade after birth and becomes the predominant isoform of adult hearts (60.4 +/- 8.5%). The 15 adult failing hearts exhibited the same isoactin pattern as the control ones (62.84 +/- 11.06%), and there was no difference in expression between patients with dilated cardiomyopathy or ischemic heart disease. These observations demonstrate that cardiac development in man, in contrast to rodent heart, is characterized by an up-regulation of the skeletal actin gene, the expression of which does not change in hypertrophied and failing hearts, and suggest that the actin and myosin heavy chain families are independently regulated in human heart.

Actins↗

PubMed1991

Cardiac hypertrophy and function in asymptomatic acromegaly.

Heart disease frequently occurs in advanced acromegaly. In order to investigate cardiac mass and function in acromegaly in the absence of obvious cardiac disease, we performed Doppler echocardiography in 15 asymptomatic acromegalic patients (six of them had systemic hypertension). The data were compared with those of a group of 10 age-matched controls. Left ventricular mass index (LVMI) was increased in acromegaly (110 +/- 32 vs 32 +/- 12 g m-2, P = 0.02), but shortening fraction and systolic time intervals did not differ. Mitral EF slope was decreased (80 +/- 21 vs 101 +/- 30 mms-1, P less than 0.02), while the duration of the isovolumic relaxation period (IRP) was increased (92 +/- 13 vs 69 +/- 16 ms, P less than 0.01). Hypertensive acromegalic patients (n = 6) had a higher LVMI than normotensive acromegalic patients (n = 9) (133 +/- 27 vs 94 +/- 24 g m-2, P = 0.02) and this was confirmed by a meta-analysis of data in the literature: the prevalence of hypertrophy was 76% in the presence of hypertension vs 50% in its absence, P less than 0.002. IRP was prolonged in normotensive acromegalic patients vs normal controls (90 +/- 11 vs 69 +/- 16 ms, P less than 0.01). In conclusion, subclinical cardiac abnormalities occur frequently in acromegaly in the absence of obvious heart disease, and hypertrophy is observed in asymptomatic hypertensive acromegaly. Moreover, diastolic abnormalities are found in asymptomatic acromegaly and could be caused by several heart-related factors.

Acromegaly↗

PubMed1991

[Myocardial involvement in 2 women, carriers of Duchenne de Boulogne muscular dystrophy].

Duchenne muscular dystrophy is the commonest genetic muscular disease. The prognosis, which depends on cardiac involvement, is poor. In boys, this takes the form of a hypokinetic cardiomyopathy particularly affecting the postero-lateral wall of the left ventricle which then dilates. The recent identification of the gene which transmits the disease on the X chromosome and of the coded protein, dystrophin, has improved our understanding of the disease. We report two cases of isolated cardiac involvement in two female carriers of the disease, classically thought to be unaffected. They presented with apparently idiopathic dilated cardiomyopathies. These cases show that Duchenne muscular dystrophy is an original example of a genetically determined diffuse muscular disease with cardiac involvement.

Adult↗

PubMed1990

Effects of indapamide on left ventricular mass and function in systemic hypertension with left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is frequently associated with hypertension and constitutes a major cardiovascular risk factor, the reduction of which should be considered when initiating antihypertensive therapy. To assess the effects of indapamide on LVH, 18 hypertensive patients were included in the study (11 men and 7 women, age 53.6 +/- 2.9 years, mean +/- standard deviation) whose supine diastolic blood pressure was greater than 95 mm Hg without (n = 11) or with (n = 7:6 beta blockers, 1 calcium antagonist) antihypertensive therapy. All presented with LVH, echocardiographically defined by a left ventricular mass index greater than 110 g/m2. After a 2-week preinclusion period, all patients received indapamide, 2.5 mg/day, for a period of 6 months. Physical examination including blood pressure measurement was performed on selection (M-1/2), before (M0), and after 1 (M1), 3 (M3) and 6 (M6) months of indapamide treatment, and echocardiography was performed at M0 and M6. Quality of life was evaluated by means of questionnaires completed by the patient and the physician, and a visual analog scale was completed by the patient at M-1/2, M0 and M6. All clinical parameters remained stable during the 2-week preinclusion period. Indapamide administration induced a highly significant reduction in both supine systolic and diastolic blood pressures from 173.9 +/- 2.9/100.5 +/- 1.2 mm Hg at M0 to 150.9 +/- 1.9/90.5 +/- 1.3 mm Hg at M1 (p less than 0.001), and 145.0 +/- 1.7/86.0 +/- 1.5 mm Hg at M6 (p less than 0.001). Similar favorable effects were observed in the upright position.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

[Heart involvement in diabetic patients].

Diabetic cardiomyopathy appears to be due to "premature ageing" of the myocardium which loses some of its compliance and becomes less sensitive to catecholamines. The condition seems to be severe mainly in those frequent cases where it is associated with hypertensive and/or ischaemic cardiomyopathy. Neuropathic denervation of the heart, usually partial and predominantly affecting the parasympathetic system, might play a part in the myocardial dysfunction. It has been held responsible for sudden death, but its real consequences in diabetic patients remain to be assessed. Coronary artery disease is the most common cardiac complication of diabetes mellitus: it accounts for 50 per cent of deaths among noninsulin-dependent, and 25 per cent among insulin-dependent diabetic subjects. Its incidence does not seem to decline and its severity, notably in women, is demonstrated by a mortality rate that is twice as high as that observed in the non-diabetic population; hence the importance of primary prevention and treatment of risk factors. However, the specificity to abnormal lipid metabolism, notably hypertriglyceridaemia, the potentiation by chronic hyperglycaemia of the harmful effects of arterial hypertension, and the possible responsibility of coagulation disorders and hyperinsulinism are points that have not yet been elucidated. We still do not know whether the objectives to be attained in terms of plasma cholesterol, triglycerides and fibrinogen levels, as well as of blood pressure values, should be different in diabetic and non-diabetic subjects. In any case, the treatment of risk factors should be accompanied by a systematic search for silent ischaemia which is 2 to 3 times more frequent among diabetic patients. Detection of silent ischaemia by electrocardiography during exercise and/or Holter recordings, and by echocardiography and/or thallium scintigraphy should be performed not only in diabetic patients with coronary artery disease but also to those with other risk factors or albuminuria.

Albuminuria↗

PubMed1990

[Beta-blockers in the treatment of heart failure].

The first attempts at treating heart failure with beta-blockers were made almost 15 years ago. A few studies, some of them controlled and randomized, suggest that beta-blockers may improve the patients' comfort, their physical capabilities, their haemodynamic values or even their life expectancy. However, the results published are conflicting. The mechanism of the beneficial effects of beta of beta-blockers is controverted, the most widely accepted hypotheses being that they protect against the toxic effect of catecholamines, act as antiarrhythmics and prevent the down regulation of beta-adrenoceptors. Numerous questions concerning the exact indications of these drugs, the nature and dosage of the beta-blocker to be used, the possible combinations with other therapies and the responses to be expected remain to be answered. When available, the results of multicentre trials currently in progress will be of assistance to determine the role of beta-blockers in the overall management of heart failure.

Adrenergic beta-Antagonists↗

PubMed1990

Factors predicting mortality in idiopathic dilated cardiomyopathy.

A study of factors predicting mortality was performed in 201 patients with dilated cardiomyopathy (163 men, 38 women, mean age: 48 +/- 11 years) by multivariate analysis (Cox Model) of 51 clinical, electrocardiographic, echocardiographic and haemodynamic parameters, 56 patients died during follow-up (mean follow-up: 57.1 +/- 29.9 months). 5 year survival was 77 +/- 3%. The following parameters were independent predictors of mortality: first symptom: pulmonary oedema, peripheral oedema, syncope; duration of symptoms at the time of inclusion; end systolic left ventricular volume; end diastolic left ventricular diameter; pulmonary artery systolic pressure; and their combination had the most accurate predictive value for death. A quantitative score (s) was calculated and used to define three subgroups: A:s less than or equal to 4.5; B: 4.5 less than s less than 6; C:s greater than or equal to 6. Five-year survival was 90 +/- 5% in group A; 84 +/- 4% in B and only 53 +/- 7% in C. In conclusion, overall survival was good in this population of all stage dilated cardiomyopathy; factors related to clinical severity, left ventricular dilation, systolic pulmonary artery pressure and duration of symptoms defined a subgroup of patients with poor prognosis.

Cardiomyopathy, Dilated↗

PubMed1990

Altered sarcoplasmic reticulum Ca2(+)-ATPase gene expression in the human ventricle during end-stage heart failure.

A decrease in the myocardial level of the mRNA encoding the Ca2(+)-ATPase of the sarcoplasmic reticulum (SR) has been recently reported during experimental cardiac hypertrophy and failure. To determine if such a deficit occurs in human end-stage heart failure, we compared the SR Ca2(+)-ATPase mRNA levels in left (LV) and right ventricular (RV) specimens from 13 patients undergoing cardiac transplantation (6 idiopathic dilated cardiomyopathies; 4 coronary artery diseases with myocardial infarctions; 3 diverse etiologies) with control heart samples using a rat cardiac SR Ca2(+)-ATPase cDNA probe. We observed a marked decrease in the mRNA for the Ca2(+)-ATPase relative to both the 18S ribosomal RNA and the myosin heavy chain mRNA in LV specimens of patients with heart failure compared to controls (-48%, P less than 0.01 and -47%, P less than 0.05, respectively). The LV ratio of Ca2(+)-ATPase mRNA to 18S RNA positively correlated with cardiac index (P less than 0.02). The RV ratio correlated negatively with systolic, diastolic and mean pulmonary arterial pressures (P less than 0.02, P less than 0.02, and P less than 0.01, respectively). We suggest that a decrease of the SR Ca2(+)-ATPase mRNA in the myocardium plays an important role in alterations of Ca2+ movements and myocardial relaxation reported during human end-stage heart failure.

Adult↗

PubMed1990

[Noninvasive evaluation of partial beta adrenergic agonist properties of xamoterol in cardiac insufficiency].

The effects of an intravenous injection of 0.15 mg/Kg of xamoterol were studied non-invasively under basal conditions and during beta-1-adrenergic stimulation with dobutamine in 16 patients with dilated cardiomyopathy and severe cardiac failure. Xamoterol did not cause any detectable agonist effect but was well tolerated under basal conditions. Its potential antagonist effect was only detected during the dobutamine infusion: xamoterol significantly reduced the increase in heart rate (p less than 0.001), the systolic blood pressure (p less than 0.01), the rate-pressure product (p less than 0.001) and the cardiac index (p less than 0.001) produced by the administration of dobutamine.

Adrenergic beta-Agonists↗

PubMed1990

[Cardiomyopathy in the peripartum period: current aspects. A multicenter study. 11 cases].

Eleven of 17 case histories recensed after an inquiry addressed to all the French university hospital cardiological departments were attributed to peripartum cardiomyopathy. Three patients (27%) needed cardiac transplantation. Predisposing factors were multiparity and twin pregnancies. Forty five per cent of patients were under 25 years of age. Hypoproteinemia was present in all serious forms of the condition. Hypoproteinemia, a cardio-thoracic ratio of over 0.60, echocardiographic left ventricular fractional shortening of under 15 per cent and presistance of symptoms after one month of medical treatment were poor prognostic factors. The relatively high incidence of myocarditis (1 out of 11 cases) justifies endomyocardial biopsy.

Adolescent↗

PubMed1990

[Effect of cardioversion of atrial fibrillation on left ventricular function in dilated cardiomyopathy. A multicenter study].

A group of 73 patients with idiopathic dilated cardiomyopathy were followed up for an average of 22 +/- 7 months to assess the medium term evolution of echocardiographic parameters of left ventricular function and, in particular, the consequences of cardioversion of atrial fibrillation. Seventy nine per cent of patients presented with cardiac failure. Left bundle branch block was observed in 20% and ventricular arrhythmias were frequent in 31%, complex in 62% with episodes of non-sustained ventricular tachycardia in 10% of cases. Left ventricular dilatation was greater in patients with complete left bundle branch block (p less than 0.003). Atrial fibrillation was present in 14 patients (19%) who were generally older than the rest of the study population (p less than 0.02) and was associated with less severe left ventricular dysfunction (p less than 0.01). Return to sinus rhythm was obtained in 9 patients. Echocardiographic data was obtained in 64 patients after an average of 6.2 +/- 1.7 months. Left ventricular function improved during the follow-up period and returned to normal in 12% of cases. Reduction of atrial fibrillation to sinus rhythm was the only predictive factor of normalisation of left ventricular function (p less than 0.02). The changes in left ventricular end diastolic dimension and fractional shortening was less marked in the group of 56 patients in sinus rhythm or chronic atrial fibrillation (normalisation of left ventricular function in 8% of cases) than in the group of 8 patients in which atrial fibrillation was converted to sinus rhythm (normalisation of left ventricular function in 50% of cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗