Non-invasive Wedensky modulation within the QRS complex.

To investigate non-invasively induced Wedensky modulation, 2ms pulses of 5, 20 and 40mA were delivered between precordial and subscapular patches synchronously with the ORS complex. Wavelet vector magnitude was obtained for averaged modulated and non-modulated complexes. The surface area of a 3D-envelope of their difference (WSR) was compared in 59 patients with an uncomplicated follow-up after myocardial infarction (MI) (42 men, 64.3+/-9.1 years), in 30 patients with ischaemic heart disease and a history of ventricular tachycardia/fibrillation (VT/VF) (29 men, 63.1+/-9.8 years), and in 53 healthy subjects (control) (22 men, 56.6+/-10.1 years). Reproducibility of the assessment was tested by computing relative errors in a sub-population of 30 VT/VF patients and 47 controls. Wedensky modulation parameters differed significantly between control, MI and VT/VF subjects. In 10 ms post-modulation windows, the following WSR values were obtained: controls: 1184+/-496 (5mA), 1553+/-838 (20 mA) and 2092+/-1488 (40 mA); VT/VF: 861+/-412 (5mA), 1134+/-636 (20 mA) and 1320+/-1036 (40 mA); MI: 1305+/-885 (5mA) and 1779+/-1169 (20 mA). With all modulating energies used, the VT/VF patients differed significantly from both the controls and MI patients; control patients against VT/VF patients: p<0.004 (5 mA), p<0.01 (20 mA) and p<0.001 (40 mA); VT/VF patients against MI patients: p<0.02 (5mA), p<0.01 (20 mA); control patients against MI patients: all p=NS. The reproducibility assessment showed an acceptable stability of Wedensky modulation parameters. This study demonstrated that wavelet decomposition detects non-invasive Wedensky modulation within the QRS complex, and VT/VF patients are less sensitive to Wedensky modulation than control and MI patients.

Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRP1 ion channel: implications for acquired and congenital long Q-T syndrome.

BACKGROUND: The voltage-gated, rapid-delayed rectifier current (I(Kr)) is important for repolarization of the heart, and mutations in the genes coding for the K+-ion channel conducting this current, i.e., KCNH2 for the alpha-subunit HERG and KCNE2 for the beta-subunit MiRP1, cause acquired and congenital long Q-T syndrome (LQTS) and other cardiac arrhythmias. METHODS: We developed a robust single-strand conformation polymorphism-heteroduplex screening analysis, with identical thermocycling conditions for all PCR reactions, covering all of the coding exons in KCNH2 and KCNE2. The method was used to screen 40 unrelated LQTS patients. RESULTS: Eleven mutations, of which six were novel, were found in KCNH2. Interestingly, six mutations were found in the region of the gene coding for the Per-Arnt-Sim (PAS) and PAS-S1 regions of the HERG protein, stressing the need to examine the entire gene when screening for mutations. No mutations were found in KCNE2, suggesting that direct involvement of MiRP1 in LQTS is rare. Furthermore, four novel single-nucleotide polymorphisms (SNPs) and one amino acid polymorphism (R1047L) were identified in KCNH2, and one novel SNP and one previously known amino acid polymorphism (T8A) were found in KCNE2. CONCLUSIONS: The potential role of rare polymorphisms in the HERG/MiRP1 K+-channel should be clarified with respect to drug interactions and susceptibility to arrhythmia and sudden death.

T-wave morphology differences between patients with and without arrhythmic complication of ischemic heart disease.

The study investigated the differences in T-wave morphology between normal controls, patients with an uncomplicated follow-up after a myocardial infarction (MI), and patients with ischaemic heart disease and a history of ventricular tachycardia/fibrillation (VT/VF). The study population consisted of 164 healthy patients (age 53.4 +/- 18.7 years old, 80 women), 123 VT/VF patients (age 63.8 +/- 10.1 years old, 15 women), and 196 MI patients (age 59.2 +/- 10.0 years old, 23 women). In all patients, supine resting signal-averaged orthogonal electrocardiograms were obtained. After singular value decomposition of electrocardiogram signal, 2 T-wave morphology descriptors were calculated: total cosine R to T describing the global angle between repolarisation and depolarisation loops, and percentage of loop area expressing the irregularity of the T-wave loop (a more irregular wave results in a lower percentage of loop area value). Both parameters were practically uncorrelated (Controls: r = - .106, MI r = .161, and VT/VF r = .173) and different between individual groups of patients: total cosine R to T (Control vs. MI: P = 4.3 x 10(-8), Control vs. VT/VF: P = 2.7 x 10(-16), MI vs. VT/VF: P = 3.1 x 10(-6)), percentage of loop area (Control vs. MI: P = 0.07, Control vs. VT/VF: P = 1.1 x 10(-8), MI vs. VT/VF: P = 2.9 x 10(-5), all nonparametric Mann-Whitney test). The comparisons of cumulative histograms also revealed significant differences between all three groups for both parameters (Kruskal-Wallis ANOVA test). Thus, these numerical descriptors of T-wave morphology are powerful indicators of arrhythmic complications among patients with ischaemic heart disease. They also differentiate between patients with stable uncomplicated ischaemic heart disease and healthy controls.

Familial mydriasis, cardiac arrhythmia, respiratory failure, muscular weakness and hypohidrosis.

OBJECTIVES: To describe a family with some sort of progressive autonomic failure in one generation (2 affected of a sibship of 7 sisters). The main features were: mydriasis, cardiac arrhythmia, cardiomegaly, hypohidrosis, respiratory failure, and muscular weakness. METHODS: Pupillometry, evaporimetry, and isokinetic power measurements were carried out. RESULTS: The autonomic dysfunction pattern (mainly cardiac abnormalities, mydriasis) seems to differ somewhat from that of progressive autonomic failure (Shy-Drager syndrome). "Lewy body-like" inclusions were present, in particular in substantia nigra, but also in locus ceruleus and raphe nuclei (cell loss only in locus ceruleus). There were no oligodendroglial, cytoplasmatic inclusions, apparently a marker in multiple system atrophy. Proper Lewy bodies were also present. Differences seemed to prevail vs the Shy-Drager syndrome. Various traits: muscular weakness pattern (e.g. preferential peroneal distribution), minor elbow contractures, and arrhythmia were reminiscent of Emery-Dreifuss muscle dystrophy (E-D). Distinguishing features included: hereditary pattern, mydriasis, and hypohidrosis. CONCLUSION: Conceivably, this disorder is close to, but still not identical with E-D.

Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen.

Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive syndrome characterised by profound congenital sensorineural deafness and prolongation of the QT interval on the electrocardiogram, representing abnormal ventricular repolarisation. In a study of ten British and Norwegian families with JLNS, we have identified all of the mutations in the KCNQ1 gene, including two that are novel. Of the nine mutations identified in this group of 10 families, five are nonsense or frameshift mutations. Truncation of the protein proximal to the recently identified C-terminal assembly domain is expected to preclude assembly of KCNQ1 monomers into tetramers and explains the recessive inheritance of JLNS. However, study of a frameshift mutation, with a dominant effect phenotypically, suggests the presence of another assembly domain nearer to the N-terminus.

Ventricular fibrillation related to reversal of the neuromuscular blockade in a patient with long QT syndrome.

The long QT syndrome (LQTS) is associated with syncopal attacks or even sudden death at a young age due to ventricular fibrillation. We report a patient with an undiagnosed LQTS who had an episode of cardiac arrest during the final part of general anesthesia, immediately after the drugs for reversal of the neuromuscular blockade were given. We suggest that the administration of glycopyrronium might have been the provoking factor in this patient.

[Rheumatoid arthritis and heart disease]. / Reumatoid artritt og hjertesykdom.

Rheumatoid arthritis is a chronic inflammatory disease that usually involves the joints, tendons and bursae. The disease is systemic and may involve the brain, peripheral nerves, lungs, kidneys, heart and blood-vessels. All anatomical structures of the heart may be involved. Most reports on rheumatoid arthritis and heart disease are case reports and autopsy studies. Sonography studies from recent years show pathology in some heart structures at about the same rate as autopsy studies. Mortality studies from the last ten years provide evidence of increased cardiovascular mortality. The frequency of reported rheumatoid heart disease differs according to the method applied in the studies. Clinically significant disease is infrequent. We describe two cases with pericarditis and give a review of the literature.

Jervell and Lange-Nielsen syndrome: a Norwegian perspective.

Jervell and Lange-Nielsen syndrome (MIM 220400; JLNS), is a rare form of profound congenital deafness combined with syncopal attacks and sudden death due to prolonged QTc; it is an autosomal recessive trait. After its first description in Norway in 1957, later reports from many other countries have confirmed its occurrence. Nowhere is the prevalence so high as in Norway, where we estimate a prevalence of at least 1:200,000. The KCNQ1 and KCNE1 proteins coassemble in a potassium channel, and mutations in either the KCNQ1 gene or the KCNE1 gene disrupt endolymph production in the stria vascularis in the cochlea, causing deafness. KCNQ1 seems to be the major gene in JLNS. Long QT syndrome (LQTS) is a separate disorder of either autosomal dominant or recessive inheritance caused by mutations in four different ion channel genes; KCNQ1 is the one most frequently involved. Some heterozygous carriers of JLNS mutations in either gene may suffer from prolonged QTc and be symptomatic LQTS patients with a need for appropriate medical treatment to prevent life-threatening cardiac arrhythmia. In general, frameshift/stop mutations cause JLNS, and missense/splice site mutations cause LQTS, but a precise genotype-phenotype correlation in LQTS and JLNS is not established, which complicates both genetic counseling and clinical risk evaluation in carriers. We review JLNS from a Norwegian perspective because of the unusually high prevalence, the genetic homogeneity associated with considerable mutational heterogeneity, and some evidence for recurrent mutational events as well as one founder mutation. We outline the clinical implications for investigation of deaf children and cases of sudden infant death syndrome as well as careful electrocardiographic monitoring of identified mutation carriers to prevent sudden death. Am. J. Med. Genet. (Semin. Med. Genet.) 89:137-146, 1999.

[Sotalol--atrial fibrillation, reduced renal function and sudden death]. / Sotalol--atrieflimmer, redusert nyrefunksjon og plutselig død.

Sotalol is a betablocker with additional antiarrythmic properties. Its pharmacokinetic properties may lead to increased serum levels of the drug in patients with reduced kidney function. We report on a case in which kidney failure in a patient using sotalol for paroxysmal atrial fibrillation gave rise to torsade de pointes ventricular tachycardia and, eventually, sudden death. Gradual prolongation of the QT interval suggested an overdose of sotalol. Sotalol has been commonly used in cases of angina pectoris and hypertension. The recently published SWORD study has, however, changed the indications for its use, and sotalol should now only be used in cases of severe supraventricular and ventricular arrythmias.

IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome.

The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes. These are caused by ventricular arrhythmias secondary to abnormal repolarisation, manifested by a prolonged QT interval on the electrocardiogram. Recently, in families with JLNS, Neyroud et al. reported homozygosity for a single mutation in KVLQT1 , a gene which has previously been shown to be mutated in families with dominantly inherited isolated long QT syndrome [Neyroud et al . (1997) Nature Genet ., 15, 186-189]. We have analysed a group of families with JLNS and shown that the majority are consistent with mutation at this locus: five families of differing ethnic backgrounds were homozygous by descent for markers close to the KVLQT1 gene and a further three families from the same geographical region were shown to be homozygous for a common haplotype and to have the same homozygous mutation of the KVLQT1 gene. However, analysis of a single small consanguineous family excluded linkage to the KVLQT1 gene, establishing genetic heterogeneity in JLNS. The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the gene IsK . This codes for a transmembrane protein known to associate with KVLQT1 to form the slow component of the delayed rectifier potassium channel. Sequencing of the affected boys showed a homozygous mutation, demonstrating that mutation in the IsK gene may be a rare cause of JLNS and that an indistinguishable phenotype can arise from mutations in either of the two interacting molecules.

[Hemopericardium with cardiac tamponade. Case reports from a coronary care unit]. / Hemoperikard med hjertetamponade. Kasuistikker fra en hjerteovervåkingsavdeling.

We describe three patients with cardiac tamponade who had been admitted to a coronary care unit, two because of rupture of the free wall during acute myocardial infarction and one because of proximal aortic dissection. Pericardiocentesis was performed in the coronary care unit after the diagnosis had been made by echocardiography. One of the patients with acute infarction and the one with proximal aortic dissection, who also underwent surgery, survived. We discuss various aspects of acute cardiac tamponade with hemopericardium.

Impact of changes in heart rate and stroke volume on the cross sectional flow velocity distribution of diastolic mitral blood flow. A study on 6 patients with pacemakers programmed at different heart rates.

The effect of changes in stroke volume on the cross sectional velocity distribution in the mitral orifice during passive mitral inflow was studied in six patients with total atrioventricular block, atrial fibrillation and VVI pacemakers during periods with different heart rates. The time velocity integrals recorded both in the left ventricular outflow tract and at the mitral orifice decreased significantly as the heart rate was increased from 60 to 80 and from 80 to 100 beats per minute. Instantaneous cross sectional flow velocity profiles were constructed by time interpolation of the velocity data from each point in sequentially delayed two dimensional digital ultrasound maps. Each patient had a characteristic cross sectional flow velocity profile in the mitral orifice recorded at the level of the leaflet tips in a four chamber view. The velocity profiles varied between the patients. With increase in heart rate only minimal changes in the flow profiles from individual patients were seen. The maximum velocity through the mitral orifice overestimated the cross sectional mean velocity at the same time by a factor of 1.4-1.9. The maximum time velocity integral overestimated the cross sectional mean by a factor of 1.4-1.8. The observed cross sectional skew varied between patients but did not change significantly with increasing heart rate and decrease in stroke volume.

MR imaging of apical hypertrophic cardiomyopathy with left ventricular endomyocardial calcification.

A rare case of apical hypertrophic cardiomyopathy with massive left ventricular endomyocardial calcification was studied with MR. The extent of the hypertrophy was clearly demonstrated, enabling accurate estimations of myocardial mass and volumes. Furthermore, an apical calcification was found and its volume estimated. In this case, MR gave the same information that was available by echocardiography, CT, and cardiac catheterization without the disadvantages of these methods.

Evolution of infarct size during the early use of nifedipine in patients with acute myocardial infarction: the Norwegian Nifedipine Multicenter Trial.

In a multicenter double-blind study, 227 patients with suspected acute myocardial infarction (AMI) were randomized within 12 hr from onset of symptoms to treatment with nifedipine (112 patients) or placebo (115 patients). AMI was confirmed in 74 patients on nifedipine and in 83 on placebo. Patients with AMI received nifedipine 5.5 +/- 2.9 hr (mean +/- SD) after onset of symptoms. Infarct size was assessed by the release of creatine kinase isoenzyme MB (CK-MB). Infarct size index (CK-MB geq/m2) was 25 +/- 16 (n = 71) in the nifedipine group and 23 +/- 13 (n = 77) in the placebo group (NS). After the first 10 mg of nifedipine systolic blood pressure fell from 147 +/- 30 to 135 +/- 28 mm Hg (p less than .01) and heart rate rose from 75 +/- 18 to 79 +/- 19 beats/min (p less than .01). No change was observed after the first placebo dose. The treatment was continued for 6 weeks. Over this period there were 10 deaths in each group. Early treatment with nifedipine in patients with AMI does not seem to reduce infarct size as determined by enzyme level.

A double-blind, crossover comparison of flecainide acetate and disopyramide phosphate in the treatment of ventricular premature complexes.

The efficacy and safety of flecainide, 200 mg twice daily, was compared with disopyramide, 150 mg 4 times daily, in a randomized, double-blind, crossover study in 25 patients (19 men and 6 women, aged 20 to 71 years, mean 52.5) with more than 1,000 ventricular premature complexes (VPCs) in a pretrial 24-hour Holter monitoring screen. Each 14-day active treatment period was preceded and followed by a 7-day placebo period. Ambulatory ECGs were recorded at the end of each study week and analyzed blindly. Average VPCs recorded during each of the 2 active periods were compared with average VPCs in the placebo periods. Twenty-two of 25 patients attained therapeutic plasma levels of both drugs. The occurrence of VPCs was significantly less during flecainide than during disopyramide treatment, 92 and 39%, respectively (p less than 0.01). Complex arrhythmic events were significantly more suppressed with flecainide than with disopyramide. No difference was observed between the 2 drugs in the incidence or severity of reported side effects. PQ, QRS and QT intervals increased beyond normal limits on both drugs in some patients, significantly more with flecainide than with disopyramide. The JT interval did not change or decrease; hence, all changes in the QT interval were attributable to a widening of the QRS complex. Neither drug showed any significant effect on blood pressure or heart rate. Flecainide may be a well-tolerated and valuable alternative to currently available antiarrhythmic agents.