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Heikki Swan

Publications and source records attributed to Heikki Swan.

25 records · Page 2Linked to original sources
PubMed2003

Functional characterization of the common amino acid 897 polymorphism of the cardiac potassium channel KCNH2 (HERG).

OBJECTIVE: To determine whether the amino acid 897 threonine (T) to lysine (K) polymorphism of the KCNH2 (HERG) potassium channel influences channel performance or patient phenotype. METHODS: The phenotypic effects of this polymorphism were investigated in vitro by electrophysiological experiments in HEK-293 cells and in vivo by exercise electrocardiography in a group of LQTS patients carrying the same genetically proven KCNQ1 mutation. RESULTS: When expressed in HEK-293 cells, the 897T isoform of the KCNH2 channel exhibited changes in inactivation and deactivation properties, and a smaller current density than the more common 897K isoform. Western blot experiments indicated that the decreased current density associated with 897T was caused by reduced channel expression. During a maximal exercise test in 39 LQT1 patients carrying an identical KCNQ1 mutation (G589D) and showing a prolonged QT interval (>440 ms), QT intervals were longer in patients carrying the 897T allele than in those homozygous for the 897K allele. CONCLUSIONS: The K897T variation has an effect on channel function and clinical phenotype. Our data warrant further investigations into the significance of this polymorphism in drug-induced and inherited LQTS.

Adolescent↗
PubMed2003

Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms.

Mutations of two myocardial calcium signaling molecules, ryanodine receptor 2 (RYR2) and calsequestrin 2 (CASQ2), may cause catecholaminergic polymorphic ventricular tachycardia (CPVT), a severe inherited arrhythmic disease manifesting with salvoes of exercise-induced bidirectional and polymorphic tachycardias. We screened 12 Finnish CPVT probands for mutations in these genes and identified three novel RYR2 mutations (V2306I, P4902L, R4959Q), which were absent in unaffected and control individuals. Although no obvious disease-causing mutations were identified in the CASQ2 gene, the molecular screening revealed two novel amino-acid polymorphisms (T66A and V76M). The frequencies of these polymorphisms in 185 unrelated probands with long QT syndrome and in 280 healthy blood donors were not significantly different. These data, combined with our previous findings, show that RYR2 mutations are present in at least 6/16 (38%) of the catecholaminergic polymorphic ventricular tachycardia families, while CASQ2 mutations must be a rare cause of CPVT.

Adult↗
PubMed2002

Ambulatory electrocardiographic evidence of transmural dispersion of repolarization in patients with long-QT syndrome type 1 and 2.

BACKGROUND: Transmural dispersion of repolarization (TDR) may be related to the genesis of torsade de pointes (TdP) in patients with the long-QT (LQT) syndrome. Experimentally, LQT2 models show increased TDR compared with LQT1, and beta-adrenergic stimulation increases TDR in both models. Clinically, LQT1 patients experience symptoms at elevated heart rates, but LQT2 patients do so at lower rates. The interval from T-wave peak to T-wave end (TPE interval) is the clinical counterpart of TDR. We explored the relationship of TPE interval to heart rate and to the presence of symptoms in patients with LQT1 and LQT2. METHODS AND RESULTS: We reviewed Holter recordings from 90 genotyped subjects, 31 with LQT1, 28 with LQT2, and 31 from unaffected family members, to record TPE intervals by use of an automated computerized program. The median TPE interval was greater in LQT2 (112+/-5 ms) than LQT1 (91+/-2 ms) or unaffected (86+/-3 ms) patients (P<0.001 for all group comparisons), and the maximal TPE values differed as well. LQT1 patients showed abrupt increases in TPE values at RR intervals from 600 to 900 ms, but LQT2 patients did so at RR intervals from 600 to 1400 ms (longest RR studied). Asymptomatic and symptomatic patients showed similar TDRs. CONCLUSIONS: TDR is greater in LQT2 than in LQT1 patients. LQT1 patients showed a capacity to increase TDR at elevated heart rates, but LQT2 patients did so at a much wider rate range. The magnitude of TDR is not related to a history of TdP.

Adult↗
PubMed2002

Association between HERG K897T polymorphism and QT interval in middle-aged Finnish women.

OBJECTIVES: The aim of this study was to test whether a recently reported polymorphism in the HERG gene coding for the rapidly activating delayed rectifier K+ channel has influence on myocardial repolarization. BACKGROUND: The length of myocardial repolarization, measured as the QT interval, has a hereditary component, but no genes that would explain the variability of repolarization have been identified in healthy subjects. METHODS: QT intervals were measured from the 12-lead electrocardiogram in a random middle-aged population (226 men/187 women). The longest QT interval at any of the 12 leads (QTmax), QTV(2), and the Tpeak-Tend interval were used as measures of repolarization. Deoxyribonucleic acid samples were genotyped for the nucleotide 2690A>C variation of the HERG gene, corresponding to the HERG K(lysine)897T(threonine) amino acid polymorphism. RESULTS: The allele frequencies were 0.84 (A) and 0.16 (C). Females with the genotype AC or CC had longer QTcmax (477 +/- 99 ms) and Tpeak-Tend intervals (143 +/- 95 ms) than females with the genotype AA (441 +/- 69 ms and 116 +/- 65 ms, p = 0.005 and p = 0.025, respectively). In males, the QTcmax and the Tpeak-Tend intervals did not differ between the genotypes. After adjustment for echocardiographic and various laboratory variables, the HERG K897T polymorphism remained as an independent predictor of QTcmax (p = 0.009) and the Tpeak-Tend intervals (p = 0.026) in females. CONCLUSIONS; The common K897T polymorphism of the HERG channel is associated with the maximal duration and transmural dispersion of ventricular repolarization in middle-aged females.

Adult↗
PubMed2002

Differentiation between LQT1 and LQT2 patients and unaffected subjects using 24-hour electrocardiographic recordings.

This study assesses the use of 24-hour ambulatory electrocardiographic recordings in distinguishing patients with long-QT1 syndrome (LQT1) from those with LQT2, and for distinguishing affected from unaffected patients. The diagnoses of the congenital LQT syndrome and its most common types LQT1 and LQT2 are made difficult because of the limitations of the electrocardiogram as a diagnostic tool. With an automated computerized program, Holter recordings from 15 LQT1 and 15 LQT2 patients and 43 healthy subjects (training set) were reviewed to select the best criteria using QT duration and rate dependence as well as the difference between QT end and QT apex to separate the 3 groups. Fixed criteria were then applied in blinded fashion to separate a different group of 32 genotyped patients and 16 unaffected subjects (test set). In the training set, the RR interval (100 ms), a slope value for median QT/RR curves of -0.016 separated 25 of 30 (83%) and a minimal QT end - QT apex value of 80 ms, separated 26 of 30 (87%) LQT1 patients from LQT2 patients. When all selected criteria were applied to differentiate LQT1 from LQT2 versus unaffected genotypes in the test set, 38 of 48 cases (79%) were correctly identified, whereas using the electrocardiogram alone, 60% of patients were correctly classified into 3 genotypes (p = 0.03). Combining measures for QT duration, rate dependence, and QT end - QT apex interval, derived from Holter recordings, complements the clinical differentiation between LQT1 versus LQT2 patients and between affected and unaffected persons for genotype screening purposes.

Adolescent↗
PubMed2002

Cardiac findings of reactive arthritis: an observational echocardiographic study.

The aim of this study was to assess echocardiographically the occurrence of cardiac abnormalities in patients with acute reactive arthritis (ReA). Eighteen consecutive adult patients with acute ReA were studied by the use of two-dimensionally guided M-mode and Doppler echocardiography. Aortic or mitral regurgitation were both detected in one of the patients. Mild to moderate left ventricular dilatation was observed in five patients, in four of whom the duration of acute ReA was over 6 months. In four patients, the ratio of peak early and peak late transmitral filling velocities was decreased. No patient had echocardiographic signs of myocarditis or pericardial effusion. In conclusion, no major structural cardiac alterations were detected. Mild valvular disease or mild to moderate left ventricular dilatation was observed in a quarter of the patients. Echocardiographic evaluation may be warranted if the acute ReA persists or has a prolonged course but is not recommended for routine use.

Adult↗