Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between July, 1967 and December, 1987, 71 children and adolescents (43 boys, 28 girls) aged from 9 days to 20 years (mean 7.8 years) underwent pacemaker implantation. In 91 p. 100 of the cases this treatment was performed for complete atrioventricular block (CAVB). Surgical CAVB was the reason for 59 p. 100 of implantations (correction of tetralogy of Fallot and, more recently, of complex cardiopathies), the second main reason (16.9 p. 100) being nonsurgical CAVB associated with heart disease; the children in this group were young (mean age 4.2 years), and the prognosis mainly depended on the heart disease. Isolated congenital CAVB accounted for only 8.5 p. 100 of pacemaker implantations; these were older children (mean age 13.7 years), and the decision to implant was often difficult to reach in the absence of major functional disorders; following implantation, it was frequently found that isolated congenital CAVBs regarded as being well tolerated in fact were unrecognized handicaps. Acquired CAVB (7 p. 100) mostly consisted of Kearns' syndrome (4/5 cases). In addition, 3 children with sinus node disease and 1 with Romano-Ward syndrome benefited from cardiac pacing. Seven children died; death was in no case due to pacing but to the heart disease associated with CAVB. Endocardial pacing (68.2 p. 100 of primary implantations during the last decade) was preferred to epicardial pacing. Since 1985 we have been using exclusively screwed endocardial monopolar electrodes. The pacemakers were usually of the single-chamber ventricular type (85.9 p. 100 of primary implantations), but since 1987 dual-chamber pacemakers have been increasingly preferred for children with permanent CAVB or for replacement of pacemaker cases. Single-chamber noncompetitive ("demand") pacemakers were implanted in only 2 children: one pacemaker was connected to a ventricular electrode (atrial paralysis), the other to an atrial electrode. Whatever the type of electrode used, the pacemakers were implanted in the abdominal region in very young infants and in the pectoral region in children older than 3 or 4 years. Breakage of the wire was the main complication. Rises in threshold are the major drawback of epicardial pacing, as they require reoperation when the energy delivered cannot be effectively programmed. Endocardial pacing, preferably with a dual-chamber instrument, seems to be the best method, being the least aggressive, with minimal complications in short and very long term; it is justified as first-line treatment of permanent or predominant CAVB.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Cardiac stimulation in children. 20 years' experience]. 313 30

The long QT syndrome is an autosomally dominantly inherited cardiac disorder characterized by abnormalities of myocardial repolarization, exercise- or stress-related syncopal attacks and risk of sudden death due to cardiac arrhythmias. Genetic linkage studies have defined three LQT loci on chromosomes 11p15.5, 3q21-24 and 7p35-36. We performed linkage analyses in three Finnish LQT families using five amplifiable markers assigned to chromosome 11p15. By multipoint linkage analyses we obtained a maximal lod score of 5.503, suggesting that the LQT1 locus maps between D11S922 and D11S1338 on chromosome 11. Our data provide a step towards closer definition of the exact borderlines of the LQT1 locus in chromosome 11 and demonstrate markers with high utility in identification of gene carriers in the affected families.
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PMID:Linkage of the long QT syndrome to the short arm of chromosome 11: use of five highly polymorphic markers towards more detailed localization of the mutant gene. 755 59

Halofantrine, increasingly used for treatment of Plasmodium falciparum malaria, is a normally well-tolerated amino-alcohol with very few side-effects, but torsades de pointes ventricular tachycardia due to halofantrine has been reported in a few patients with a congenital long QT interval (Romano-Ward syndrome). We performed a prospective study of the cardiac effect of halofantrine in 20 patients with 48 h ambulatory electrocardiographic (ECG) monitoring; the halofantrine levels in their serum were also determined. Minimal ECG changes were noted, with lengthening of the QT interval without clinical symptoms. This effect was dose-dependent and can be very severe in cases of pre-existing cardiopathy; it also occurs in patients without any pre-existing cardiopathy. In order to reduce the likelihood of such incidents, which are admittedly rare, we suggest performing electrocardiography on all patients before initiating treatment with halofantrine.
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PMID:Cardiac complications of halofantrine: a prospective study of 20 patients. 757 Aug 88

Eighteen patients with long QT interval and recurrent ventricular tachycardia, torsade de pointe, were studied. Fourteen patients had an underlying heart disease. The factors involved in the appearance of this arrhythmia were: antiarrhythmic drugs (55.5%), complete heart block (33.5%), Romano-Ward syndrome (5.5%) and hypokalemic periodic paralysis (5.5%). In drug-induced torsade de pointe the QT interval was moderately prolonged. Seven patients (70%) had hypokalemia and 5 patients were bradycardic (50%). In patients with heart block-induced torsade de pointe, the QT interval was markedly prolonged. The ventricular rate was markedly slow (38 beat/min +/- 6 SD), and hypokalemia was less obvious (33.3%). In all cases there were ventricular extrasystoles with bigeminy, couplets or polymorphism on the basic ECG. Long-short sequence initiating the torsade de pointe was observed in 83 out of the 92 episodes. The withdrawal of the offensive drug or the correction of a treatable cause was sufficient to prevent torsade de pointe while the use of isoproterenol was effective in 7 patients who received this drug alone or prior to the ventricular pacing which was successfully used in 9 patients. Lidocaine was ineffective or had deleterious effects in 15 patients where electrical cardioversion required repeated use with an average of 5 times/patient.
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PMID:Torsade de pointe. Report of 18 cases. 805 45

Incidence and malignant forms of imported Plasmodium falciparum malaria are increasing, and chemoprevention is more and more replaced by stand-by treatment and radical cure in preventing access on return from malaria areas. Halofantrine is recommended for this radical cure: it's an habitually well-tolerated amino-alcohol with very few side-effects. We report three cases of long QT-interval due to halofantine: three different young women coming back from Africa took halofantrine (500 mg (2 tablets) six hourly for three doses on the first and the seventh day) and all presented with syncopal episodes. Serum electrolyte concentrations and echocardiograms were normal. In one case only, a diagnosis of Plasmodium falciparum malaria was made, without severe manifestations, and in the two other cases, treatment was a radical cure. In two cases, several bursts of torsades de pointes ventricular tachycardia due to halofantrine were proven and electrophysiological cardiac tests concluded that they had a congenital long QT-interval/Romano-Ward syndrome). So far halofantrine cardiac toxicity was unknown with single dose of 24 mg/kg/d. This phenomenon can be very severe in case of preexisting cardiopathy. In spite of the rarity on the congenital Romano-Ward syndrome, systematic electrocardiogram is necessary before giving halofantrine.
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PMID:[Ventricular arrhythmia and halofantrine intake. Probable deleterious effect. Apropos of 3 cases]. 812 7

Inward rectifying potassium currents (Ikr and Iks) during phase 3 repolarization of the myocyte from the beginning to the end of repolarization of the myocardial syncytium will inscribe a T-U-wave on the surface electrocardiogram (ECG). Type two congenital long QT syndrome (LQT2) is a phenotype of human ether-a-go-go-related gene (HERG) mutation on the chromosome 7q 35-36. Type one congenital long QT syndrome (LQT1) is a phenotype of KvLQT1 mutation on the chromosome 11p15.5. Both LQT1 and LQT2 relate with inward rectifying potassium currents and is repolarization related, therefore, it is speculate that patients of LQT1 and LQT2 may have an abnormal T-U-wave on their surface ECG. To two probands of congenital LQT, 8 patients of structural heart disease treated by open heart surgery, 13 patients of structural heart disease without open-heart surgery, and 10 patients of normal controls, 24 hour-Holter monitoring was performed from July to December 1996. Their corrected QT interval (QTc) as well as the RR interval of every heart beat was calculated by a computer. The results showed that all 33 patients exhibited beat-by-beat fluctuation of their QTc and RR daily. The RR intervals of these two probands of congenital LQT were somewhile more than 1200 ms during circadian waking time, while 31 cases without LQT showed their RR prolongation only during the circadian sleeping time. A multi-undulant T-U-wave, or a beat-to-beat changing of vectors or amplitudes of their T-U-wave observed in these two probands of congenital LQT, were not observable in those 31 patients without congenital LQT. Therefore, we concluded that multi-undulant T-U-wave, sinus bradycardia and a longer QTc was a phenotype of the mutated genes which control the inward rectifying potassium currents during phase 3 repolarization.
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PMID:Multi-undulant T-U-wave, sinus bradycardia and long QT syndrome: a possible phenotype of mutant genes controlling the inward potassium rectifiers. 929 27

Long QT syndrome (LQT) is a cardiac disorder that causes sudden death from ventricular tachyarrhythmias, specifically torsade de pointes. Two types of LQT have been reported, autosomal-dominant LQT (Romano-Ward syndrome) and autosomal-recessive LQT (Jervell and Lange-Nielsen syndrome); Jervell and Lange-Nielsen syndrome is also associated with deafness. Four LQT genes have been identified for autosomal-dominant LQT: K+ channel genes KVLQT1 on chromosome 11p15.5, HERG on 7q35-36 and minK on 21q22, and the cardiac Na+ channel gene SCN5A on chromosome 3p21-24. Two genes, KVLQT1 and minK, have been identified for Jervell and Lange-Nielsen syndrome. Genetic testing and gene-specific therapies are available for some LQT patients.
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PMID:The molecular basis of long QT syndrome and prospects for therapy. 979 61

The long QT syndrome (LQTS) is a heart disorder which is characterised by the prolongation of the QT interval of the surface electrocardiogram and is associated with malignant arrhythmias, syncopal episodes, torsade de pointes form ventricular tachycardias and an increased risk of sudden cardiac death. There are two familial forms of LQTS, the autosomal dominant Romano-Ward syndrome and the autosomal recessive Jervell-Lange-Nielsen syndrome which is associated with congenital senzorineural deaf-mutism. Recent advances in molecular genetics have allowed to identify mutations in four genes, KvLQT1 (11p15.5), HERG (7q35), SCN5A (3p21) and minK (21q22), which cause LQTS. There is a fifth genetic locus known on chromosome 4 (4q25-27), where the disease causing gene has not been identified yet. As LQTS genes code proteins which form sodium and potassium channels of the heart, LQTS can be regarded as the disease of cardiac ion channels. The KvLQT1 and minK genes code the slowly activating, delayed rectifier (Iks) potassium channel, the HERG gene code the rapidly activating, delayed rectifier (Ikr) potassium channel of the heart, while the SCN5A gene codes a cardiac sodium channel. Mutations in KvLQT1, minK and HERG genes affects repolarising, rectifier potassium currents, while SCN5A mutations cause delayed inactivation and reopening of the cardiac sodium channel, which initiates the depolarisation of cardiac cells. Both alterations result in a prolongation of cardiac repolarisation which is represented in the elongation of the QT interval. Elucidation of the genetic base of the disease provided new tools in the clinical management of LQTS. It has been shown that changes in the repolarisation parameters on the ECG may be predictive for the causative gene and different LQTS genes are associated with different clinical picture. More importantly, it is possible to use "gene-specific" therapy in LQTS which specifically targets ion channels affected by given gene mutations.
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PMID:[Molecular genetics of the long QT syndrome: clinical aspects]. 1061 47

The prolonged QT syndromes are characterized by prolongation of the QT interval corrected for heart rate (QTc) on the surface electrocardiogram associated with T-wave abnormalities, relative bradycardia, and ventricular tachyarrhythmias, including polymorphic ventricular tachycardia and torsades de pointes. These patients tend to present with episodes of syncope, seizures, or sudden death typically triggered by exercise, emotion, noise, or, in some cases, sleep. These disorders of cardiac repolarization are commonly inherited, with the autosomal dominant form, Romano-Ward syndrome, most common. A rare autosomal recessive form associated with sensorineural deafness, Jervell and Lange-Nielsen syndrome, in which the cardiac disorder is autosomal dominant and deafness is a recessive trait, also occurs. The underlying genetic causes of these forms of prolonged QT interval syndromes are heterogeneous, with at least seven genes responsible for the clinical syndromes. All of the five genes identified to date encode ion channel proteins, suggesting this to be an ion channelopathy. In this review, the genetic basis of the prolonged QT interval syndromes will be discussed, genotype-phenotype correlations identified, and the approaches to genetic testing and treatments will be outlined.
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PMID:Molecular biology and the prolonged QT syndromes. 1128 54

The long-QT syndrome (LQTS) is an inherited cardiac disorder associated with syncope and a high risk of sudden death. The molecular basis of type-1 LQTS (LQT1) is a missense or nonsense mutation in KCNQ channels that reduces slowly activating delayed rectifier potassium channel (I(Ks)) resulting in a prolonged action potential. Noticeably, the S2-S3 linker is a highly congregating region of LQT1 mutations. To further explore the mechanism, a KCNQ mutant (L191P) identified in one Chinese pedigree with LQT1 was chosen for this purpose. As Leu-191 is located in the middle of a well-known endoplasmic reticulum (ER) localization signal (RXR) in the intracellular S2-S3 linker, we examined the kinetics and the surface expression of both the KCNQ1 and L191 mutants. Our results showed that the mutation did not affect the channel kinetics, whereas the surface expression increased with increasing hydrophobicity of the middle residue 'X' of the RXR motif. Based on an analysis of fractional fluorescence data using a binomial model, we also found that the percentage of KCNQ1/L191P heteromeric channels expressed at the cell surface were 22.0%, 40.5%, 27.9%, 8.6% and 1.0% of heteromeric channels with 0, 1, 2, 3 and 4 subunits of L191P, respectively, in a transfected ratio of KCNQ1: L191P=1:1. These experiments demonstrated that coexpression of L191P resulted in a trafficking factor alpha<1, causing a trafficking deficiency of heteromeric channels that underlay the dominant-negative effect. This study suggests several trafficking signals coexisting in this region, and expands our understanding of possible dominant-negative mechanisms underlying LQTS.
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PMID:A hydrophobicity-dependent motif responsible for surface expression of cardiac potassium channel. 1904 15


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