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Biomedical subjects

Lauri Toivonen

Publications and source records attributed to Lauri Toivonen.

At least 19 recordsLinked to original sources
PubMed2006

Beta1-adrenergic receptor polymorphisms, QTc interval and occurrence of symptoms in type 1 of long QT syndrome.

BACKGROUND: The most prevalent LQT1 form of inherited long QT syndrome is caused by mutations of the KCNQ1 gene resulting repolarizing I(Ks) potassium current to decrease and the QT interval to prolong. As abrupt sympathetic activation triggers ventricular arrhythmias that may cause syncopal attacks and sudden death in LQT1 patients, we investigated whether two known beta1-adrenergic receptor polymorphisms were associated with the duration of QT interval or history of symptoms in LQT1. METHODS: We determined beta1-adrenergic receptor polymorphisms (Ser49Gly and Arg389Gly) in 168 LQT1 patients. We also reviewed each patient's clinical records on the history of long QT syndrome-related symptoms and measured QT intervals from baseline ECG in each subject and from an exercise test ECG in 55 LQT1 patients. RESULTS: Patients with the homozygous Arg389Arg genotype tended to have shorter and those with the Ser49Ser genotype longer QT intervals than patients with other genotypes, but neither polymorphism studied alone affected the risk of symptoms. In contrast, adjusted odds ratio for the history of symptoms was 4.9 (95% CI 1.18 to 20.3) in patients homozygous for both Ser49 and Arg389. These double homozygous patients showed similar QT intervals as the rest of the LQT1 cohort. CONCLUSIONS: In this relatively small study, double homozygosity for Arg389 and Ser49 of the human beta1-adrenergic receptor associated with the risk of symptoms in LQT1. The association between these beta1-adrenergic receptor polymorphisms and the symptom history in LQT1 is not mediated via QT interval duration.

Adolescent↗
PubMed2006

Effect of physical training on ventricular repolarization in type 1 long QT syndrome: a pilot study in asymptomatic carriers of the G589D KCNQ1 mutation.

AIMS: High-intensity physical exercise and competitive sports have been traditionally avoided in long QT syndrome. However, endurance training increases vagal activity and thus may improve cardiac electrical stability in healthy subjects. We hypothesized that controlled submaximal endurance training would not adversely affect ventricular repolarization in asymptomatic carriers of a KCNQ1 gene mutation of type 1 long QT syndrome (LQT1). METHODS AND RESULTS: Previously, sedentary carriers of a missense mutation of KCNQ1 gene (LQT1, n=7) and healthy controls (n=8) exercised on a bicycle ergometer 3-4 times a week, 30 min a day at 60-75% of maximal heart rate (HR) for a maximum of 3 months. Body surface potential mapping (BSPM) was recorded and QT intervals were determined automatically from 14 channels over the left chest area. Maximal work capacity increased by 4+/-1% in LQT1 and by 14+/-2% in controls (both P<0.05), and left ventricular (LV) mass by 8+/-1% and 9+/-1%, respectively (P<0.05). Resting corrected QT interval shortened by 10+/-1% (P<0.05) and QT interval dispersion by 25+/-9% (P<0.05) in LQT1, but not significantly in controls. QT intervals at specified HRs during workload and recovery phases were not changed in either group. CONCLUSION: In this pilot study of asymptomatic carriers of a KNCQ1 gene mutation, submaximal endurance training did not harmfully affect arrhythmia risk markers. Confirmatory studies in a broader spectrum of LQT1 genotypes are needed before any generalization can be made.

Adult↗
PubMed2006

Effects of beta-blocker therapy on ventricular repolarization documented by 24-h electrocardiography in patients with type 1 long-QT syndrome.

OBJECTIVES: We tested the hypothesis that in long-QT syndrome (LQT) type 1 (LQT1), beta-blocker therapy may decrease both the diurnal maximal T-wave peak to T-wave end interval (TPE) and the maximal ratio between late and early T-wave peak amplitude (T2/T1 ratio), which are electrocardiographic counterparts of transmural dispersion of repolarization (TDR) and early afterdepolarizations (EA), respectively. BACKGROUND: Ventricular repolarization duration and increased TDR and EAs are the three electrophysiological components generating the high risk of ventricular arrhythmias and sudden death in the inherited LQT. In the most prevalent LQT1 form of LQT, treatment with beta-blockers reduces serious arrhythmia events dramatically without a known influence on QT interval duration. In experimental LQT1 models, beta-blockers decrease TDR and prevent EAs. METHODS: We reviewed 24-h electrocardiographic recordings obtained before and during the treatment with beta-blockers from 24 genotyped LQT1 patients to record maximal TPE intervals and T2/T1 ratios as well as maximal and rate-adapted QT intervals using a computer-assisted program. RESULTS: Treatment with beta-blockers decreased the maximal diurnal T2/T1 amplitude ratio from 3.0+/- 1.0 to 2.2 +/- 0.6 (p = 0.002). Beta-blockers also decreased both maximal TPE intervals and abrupt maximal QT intervals at heart rates higher than 85 beats/min, whereas QT intervals measured at steady-state conditions remained unchanged. CONCLUSIONS: Prevention of abrupt increases of electrocardiographic TDR, EA, and ventricular repolarization duration at elevated heart rates may explain the favorable clinical effects of beta-blockers in LQT1.

Adolescent↗
PubMed2006

The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome.

BACKGROUND: Data on the Jervell and Lange-Nielsen syndrome (J-LN), the long-QT syndrome (LQTS) variant associated with deafness and caused by homozygous or compound heterozygous mutations on the KCNQ1 or on the KCNE1 genes encoding the I(Ks) current, are still based largely on case reports. METHODS AND RESULTS: We analyzed data from 186 J-LN patients obtained from the literature (31%) and from individual physicians (69%). Most patients (86%) had cardiac events, and 50% were already symptomatic by age 3. Their QTc was markedly prolonged (557+/-65 ms). Most of the arrhythmic events (95%) were triggered by emotions or exercise. Females are at lower risk for cardiac arrest and sudden death (CA/SD) (hazard ratio, 0.54; 95% CI, 0.34 to 0.88; P=0.01). A QTc >550 ms and history of syncope during the first year of life are independent predictors of subsequent CA/SD. Most mutations (90.5%) are on the KCNQ1 gene; mutations on the KCNE1 gene are associated with a more benign course. beta-Blockers have only partial efficacy; 51% of the patients had events despite therapy and 27% had CA/SD. CONCLUSIONS: J-LN syndrome is a most severe variant of LQTS, with a very early onset and major QTc prolongation, and in which beta-blockers have limited efficacy. Subgroups at relatively lower risk for CA/SD are identifiable and include females, patients with a QTc < or =550 ms, those without events in the first year of life, and those with mutations on KCNE1. Early therapy with implanted cardioverter/defibrillators must be considered.

Adolescent↗
PubMed2006

Quality of emergency room care for atrial fibrillation.

OBJECTIVES: Atrial fibrillation (AF) is the most common arrhythmia in emergency rooms (ER). We surveyed the clinical characteristics and quality of care of AF patients in three emergency rooms in Helsinki, Finland. DESIGN: Observational data of the treatment of 179 consecutive symptomatic AF patients were prospectively collected. The quality of care was analysed according to a predestined set of criteria. RESULTS: Mean age of the patients was 63 years and 61% were men. The leading symptom was palpitation (86%). Sinus rhythm was achieved in 70%. New anticoagulation was initiated in 20% and cardiovascular medication modified in 42% of patients. Considering the overall quality of care, including documentation in the patient chart, it was classified as good in 53% of all patients, whereas the quality of therapeutic decisions and planning for follow-up was good in 77%. CONCLUSIONS: The ER visit results in extensive treatment modifications in two of three patients. Although inadequate care is rare, maintaining good quality requires adherence to clinical guidelines, careful documentation and plans for follow-up.

Adult↗
PubMed2006

QRS duration in high-resolution methods and standard ECG in risk assessment after first and recurrent myocardial infarctions.

BACKGROUND: Prolonged QRS duration (QRSd) is associated with increased mortality after myocardial infarction (MI). Only little data exist about its predictive ability and relationships to clinical variables in the present era of active treatment of myocardial ischemia and cardiac dysfunction. We investigated whether QRSd in high-resolution methods and standard ECG predict arrhythmic events and cardiac death in post-infarction patients with cardiac dysfunction and how it relates to clinical variables, with a special emphasis on history of previous MI. METHODS AND RESULTS: Patients (n = 158) with acute MI and cardiac dysfunction had magnetocardiography (MCG), signal-averaged ECG (SAECG), and ECG registered at discharge. Patients with a previous MI had significantly longer QRSd although their left ventricular function was almost similarly impaired. During the mean follow-up of 50 +/- 15 (range 1-72) months, 32 patients died and 17 (53%) of the deaths were classified as cardiac. Eighteen patients had an arrhythmic event. QRSd >121 ms in MCG and >114 ms in SAECG were significant predictors of arrhythmic events and cardiac death, whereas QRSd in ECG predicted only cardiac death. In multivariate analysis, QRSd in MCG (hazard ratio (HR) = 3.6, P = 0.007) and SAECG (HR = 4.6, P = 0.016) predicted only arrhythmic events, whereas QRSd in ECG was an independent predictor of cardiac death. CONCLUSIONS: Prolonged QRSd in MCG and SAECG are powerful indicators of the arrhythmia substrate in post-infarction patients with cardiac dysfunction, whereas prolonged QRSd in standard ECG associates with increased risk of cardiac death.

Algorithms↗
PubMed2006

Ventricular repolarization and heart rate responses during cardiovascular autonomic function testing in LQT1 subtype of long QT syndrome.

BACKGROUND: In the most prevalent LQT1 form of inherited long QT syndrome symptoms often occur during abrupt physical or emotional stress. Sympathetic stimulation aggravates repolarization abnormalities in experimental LQT1 models. We hypothesized that autonomic function tests might reveal the abnormal repolarization in asymptomatic LQT1 patients. METHODS: We measured heart rates (HRs) and QT intervals in nine asymptomatic carriers of a C-terminal KCNQ1 mutation and 8 unaffected healthy subjects using an approach of global QT values derived from 28 simultaneous electrocardiographic leads on beat-to-beat base during Valsalva maneuver, mental stress, sustained handgrip, and light supine exercise. RESULTS: LQT1 patients exhibited impaired shortening of both QTpeak and QTend intervals during autonomic interventions but exaggerated lengthening of the intervals--a QT overshoot--during the recovery phases. The number of tests with a QT overshoot was 2.4 +/- 1.7 in LQT1 patients and 0.8 +/- 0.7 in unaffected subjects (P = 0.02). Valsalva strain prolonged T wave peak to T wave end interval (TPE) in LQT1 but not in unaffected patients. LQT1 patients showed diminished HR acceleration in response to adrenergic challenge whereas HR responses to vagal stimuli were similar in both groups. CONCLUSIONS: Standard cardiovascular autonomic provocations induce a QT interval overshoot during recovery in asymptomatic KCNQ1 mutation carriers. Valsalva maneuver causes an exaggerated fluctuation of QT and TPE intervals partly explaining the occurrence of cardiac events during abrupt bursts of autonomic activity in LQT1 patients.

Adult↗
PubMed2006

Increased intra-QRS fragmentation in magnetocardiography as a predictor of arrhythmic events and mortality in patients with cardiac dysfunction after myocardial infarction.

INTRODUCTION: Increased intra-QRS fragmentation score (FRA) in magnetocardiography (MCG) has shown association with sustained ventricular arrhythmias in post-MI patients suggesting its relation to arrhythmia substrate. The aim of this study was to investigate whether increased FRA in MCG predicts arrhythmic events and mortality after acute myocardial infarction (MI) with cardiac dysfunction. METHODS AND RESULTS: A series of 158 patients with acute MI and left ventricular ejection fraction (LVEF) <50% were studied. Their age was 60 +/- 10 years and LVEF 40 +/- 6%. MCG was registered and FRA was computed. For comparison, QRS duration in 12-lead ECG was measured. In a mean follow-up of 50 +/- 15 months, 32 (20%) patients died and 18 (11%) had an arrhythmic event. Both arrhythmic event rate and all-cause mortality were significantly higher in patients with increased FRA (P < 0.001 for both). In contrast, increased QRS duration in ECG predicted all-cause mortality (P < 0.05) but not arrhythmic events. In multivariate analysis, FRA was an independent predictor of both arrhythmic events and all-cause mortality. Using a combined criterion of increased FRA and LVEF < 30% yielded positive and negative predictive accuracies of 50% and 91% for arrhythmic events. CONCLUSION: In post-MI patients with left ventricular dysfunction, increased intra-QRS fragmentation in high-resolution magnetocardiography predicts arrhythmic events, whereas QRS duration in 12-lead ECG predicts all-cause mortality. Analysis of intra-QRS fragmentation by MCG may assist in guiding therapy of post-MI patients, for example, by selecting those who would benefit most from prophylactic implantable cardioverter-defibrillator therapy.

Arrhythmias, Cardiac↗
PubMed2006

Magnetocardiographic assessment of healed myocardial infarction.

BACKGROUND: We evaluated the capability of multichannel magnetocardiography (MCG) to detect healed myocardial infarction (MI). METHODS: Multichannel MCG over frontal chest was recorded at rest in 21 patients with healed MI, detected by cine- and contrast-enhanced magnetic resonance imaging, and in 26 healthy controls. Of the 21 MI patients, 11 had non-Q wave and 10 Q wave MIs. QRS, ST-segment, T wave and ST-T wave integrals, ST-segment and T wave amplitudes, and QRS and ST-T wave magnetic field map orientations were measured. RESULTS: The MCG repolarization indexes, such as ST segment and ST-T wave integrals, separated the MI group from the controls (ST-T wave integral -1.4 +/- 5.3 vs 1.5 +/- 4.7 pTs, P = 0.034). The abnormalities were more distinct in the Q wave-MI than in the non-Q wave MI subgroup. In the latter, however, a trend similar to the Q wave MI group was found. The relation of QRS area to ST segment and T wave integral improved the detection of healed MIs compared to the ST-T wave indexes alone (QRS-ST-T discordance 14 +/- 10 vs 5.0 +/- 7.1 pTs, P = 0.003). When comparing the MI group to the controls, the orientation of the magnetic field maps differed in the ST-T wave maps (163 +/- 119 degrees vs 58 +/- 17 degrees, P < 0.001) but not in the QRS maps (111 +/- 95 degrees vs 106 +/-93 degrees, P = 0.646). CONCLUSIONS: The MCG repolarization variables can detect healed MI. These ST-T wave abnormalities are more pronounced in patients with Q wave MI than in patients with non-Q wave MIs. Relating the signals of depolarization and repolarization phases improves the detection of healed MI. Repolarization abnormalities are common in healed MI and thus should not always be interpreted as present ongoing ischemia.

Aged↗
PubMed2006

Reproducibility of computerized measurements of QT interval from multiple leads at rest and during exercise.

BACKGROUND: Accurate measurement of the QT interval is important for diagnosing long QT syndrome (LQTS), and in research on determinants of ventricular repolarization time. We tested automatic analysis of QT intervals from multiple ECG leads on chest. METHODS: Eleven healthy volunteers and 10 genotyped LQTS patients were tested at rest and during exercise with a bicycle ergometer twice 1-31 months apart. Electrocardiograms were recorded with the body surface potential mapping system, and 12 precordial channels were selected for analysis. Averaged QT peak and QT end intervals were determined with an automated algorithm, and the difference QT end minus QT peak (Tp-e) was calculated. Repeatability was assessed by coefficient of variation (CV) between measurements. RESULTS: Within one test at rest the QT end intervals were highly repeatable with CV 0.6%. In repeated tests CV was 4.4% for QT end interval and 3.5% when the QT interval was corrected for heart rate. In exercise test at specified heart rates, mean CV was 3.0% for QT end and 2.9% for QT peak interval. The CV of Tp-e interval was 10.2% at rest, and 9.3% in exercise test. Reproducibility was comparable between healthy subjects and LQTS patients. CONCLUSIONS: The BSPM system with automated analysis produced accurate and highly repeatable QT interval measurements. Reproducibility was adequate also over prolonged time periods both at rest and in exercise stress test. The method can be applied in studying duration of ventricular repolarization time in different physiologic and pharmacologic interventions.

Adult↗
PubMed2005

Electrocardiographic strain pattern and prediction of new-onset congestive heart failure in hypertensive patients: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study.

BACKGROUND: The ECG strain pattern of ST depression and T-wave inversion is strongly associated with left ventricular hypertrophy (LVH) independently of coronary heart disease and with an increased risk of cardiovascular morbidity and mortality in hypertensive patients. However, whether ECG strain is an independent predictor of new-onset congestive heart failure (CHF) in the setting of aggressive antihypertensive therapy in unclear. METHODS AND RESULTS: The relationship of ECG strain at study baseline to the development of CHF was examined in 8696 patients with no history of CHF who were enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. All patients had ECG LVH by Cornell product and/or Sokolow-Lyon voltage criteria on a screening ECG, were treated in a blinded manner with atenolol- or losartan-based regimens, and were followed up for a mean of 4.7+/-1.1 years. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite the QRS axis in lead V5 or V6. ECG strain was present in 923 patients (10.6%), and new-onset CHF occurred in 265 patients (3.0%), 26 of whom had a CHF-related death. Compared with patients who did not develop CHF, hypertensive patients who developed CHF were older; were more likely to be black, current smokers, and diabetic; were more like to have a history of myocardial infarction, ischemic heart disease, stroke, or peripheral vascular disease; and had greater baseline severity of LVH by Cornell product and Sokolow-Lyon voltage, higher baseline body mass indexes, higher serum glucose levels and albuminuria, similar baseline systolic and diastolic pressures, and reductions in diastolic pressure with treatment but greater reductions in systolic pressure. In univariate Cox analyses, ECG strain was a significant predictor of new-onset CHF (hazard ratio [HR], 3.27; 95% CI, 2.49 to 4.29) and CHF mortality (HR, 4.74; 95% CI, 2.11 to 10.64). In Cox multivariable analyses adjusting for baseline differences between patients with and without new-onset CHF, in-treatment differences in systolic and diastolic pressures, Sokolow-Lyon voltage, and Cornell product, and the impact of treatment with losartan versus atenolol on outcomes, ECG strain remained a significant predictor of incident CHF (HR, 1.80; 95% CI, 1.30 to 2.48) and CHF-related death (HR, 2.78; 95% CI, 1.02 to 7.63). CONCLUSIONS: ECG strain identifies hypertensive patients at increased risk of developing CHF and dying as a result of CHF, even in the setting of aggressive blood pressure lowering.

Aged↗
PubMed2005

Ratio of late to early T-wave peak amplitude in 24-h electrocardiographic recordings as indicator of symptom history in patients with long-QT Syndrome types 1 and 2.

UNLABELLED: We reviewed 24-h electrocardiographic recordings from 214 genotyped subjects--97 with long-QT syndrome type 1 (LQT1), 62 with LQT2, and 55 unaffected--to record maximal diurnal amplitude ratios between late and early T-wave peaks. Maximal amplitude ratios between late and early T-wave peaks were higher in symptomatic than in asymptomatic patients both in LQT1 (3.2 +/- 1.0 vs. 2.3 +/- 0.8; p < 0.001) and in LQT2 patients (2.6 +/- 1.0 vs. 1.7 +/- 0.5; p < 0.001). The maximal amplitude ratio between late and early T-wave peaks was independently associated with symptom history in both LQT1 and LQT2 patients. OBJECTIVES: We tested the hypothesis that in long-QT syndrome types 1 (LQT1) and 2 (LQT2), the diurnal maximal ratio between late and early T-wave peak amplitudes correlates with a history of symptoms better than QT interval durations. BACKGROUND: Genotype and phenotype studies have delineated clinical profiles of the most prevalent LQT1 and LQT2 subtypes of inherited LQT, but prediction of arrhythmia risk remains uncertain, the baseline QTc interval being the best predictor. In experimental long-QT syndrome models, the ratio between late and early T-wave peak amplitude predicts onset of torsade de pointes. METHODS: We reviewed 24-h electrocardiographic recordings from 214 genotyped subjects--97 with LQT1, 62 with LQT2, and 55 unaffected-to record maximal amplitude ratios between late and early T-wave peaks by use of a computer-assisted program. RESULTS: Maximal amplitude ratios between late and early T-wave peaks were higher in symptomatic than in asymptomatic patients both in LQT1 (3.2 +/- 1.0 vs. 2.3 +/- 0.8; p < 0.001) and LQT2 patients (2.6 +/- 1.0 vs. 1.7 +/- 0.5; p < 0.001). Although the QTc interval also was longer in symptomatic patients, only the maximal amplitude ratio between late and early T-wave peaks was independently associated with symptoms in both LQT1 and LQT2 patients. CONCLUSIONS: Maximal diurnal ratio between late and early T-wave peak amplitude improves noninvasive risk assessment both in LQT1 and LQT2 syndromes. We propose this new indicator in clinical evaluation of arrhythmia risk in LQT1 and LQT2.

Adult↗
PubMed2005

Catecholaminergic polymorphic ventricular tachycardia: recent mechanistic insights.

Cardiac excitation-contraction coupling occurs by a calcium ion-mediated mechanism in which the signal of action potential is converted into Ca2+ influx into the cardiomyocytes through the sarcolemmal L-type calcium channels. This is followed by Ca2+-induced release of additional Ca2+ ions from the lumen of the sarcoplasmic reticulum into the cytosol via type 2 ryanodine receptors (RyR2). RyR2 channels form large complexes with additional regulatory proteins, including FKBP12.6 and calsequestrin 2 (CASQ2). Catecholamines, released into the body fluids during emotional or physical stress, activate Ca2+-induced Ca2+ release by protein kinase A-mediated phosphorylation of RyR2. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an insidious, early-onset and highly malignant, inherited disorder characterized by effort-induced ventricular arrhythmias in the absence of structural alterations of the heart. At least some cases of sudden, unexplained death in young individuals may be ascribed to CPVT. Mutations of the RyR2 gene cause autosomal dominant CPVT, while mutations of the CASQ2 gene may cause an autosomal recessive or dominant form of CPVT. The steps of the molecular pathogenesis of CPVT are not entirely clear, but inappropriate "leakiness" of RyR2 channels is thought to play a role; the underlying mechanisms may involve an increase in the basal activity of the RyR2 channel, alterations in its phosphorylation status, a defective interaction of RyR2 with other molecules or ions, such as FKBP12.6, CASQ2, or Mg2+, or its abnormal activation by extra- or intraluminal Ca2+ ions. Beta-adrenergic antagonists have proven to be of value in prevention of arrhythmias in CPVT patients, but occasional treatment failures call for alternative measures. There is great interest at present for the development of novel antiarrhythmic drugs for CPVT, as the same approaches may be applied for treatment of more common forms of life-threatening arrhythmias, such as those arising during ischemia and heart failure.

Animals↗
PubMed2005

Measurement and reproducibility of magnetocardiographic filtered atrial signal in patients with paroxysmal lone atrial fibrillation and in healthy subjects.

Magnetocardiography (MCG) is a method complementary to electrocardiography (ECG). We examined recording and reproducibility of atrial depolarization signal by MCG. Multichannel MCG over anterior chest and orthogonal 3-lead ECG were recorded in 9 patients who had paroxysmal lone atrial fibrillation and in 10 healthy subjects in duplicate at least 1 week apart. Data were averaged using atrial wave template and high-pass filtered at 25, 40, and 60 Hz. Atrial signal duration with automatic detection of onset and offset and root mean square amplitudes of the last portion of atrial signal were determined. Coefficient of variation of atrial signal duration by MCG at 40 Hz was 3.3% and difference between the measurements was 3.5 milliseconds on average. The corresponding figures obtained by signal-averaged ECG (SAECG) were 6.1% and 6.9 milliseconds. Coefficient of variation for root mean square of the last 40 milliseconds of atrial signal were 16% in MCG and 17% in SAECG. Reproducibility was best at 40-Hz filter and similar in patients and healthy subjects. In conclusion, the reproducibility of atrial signal variables in MCG is adequate and somewhat better than in SAECG and equal in patients with lone atrial fibrillation and healthy subjects. Magnetocardiography seems to be a potentially valuable method to evaluate features of atrial depolarization in patient studies.

Adult↗
PubMed2005

Spatial repolarization abnormalities in old myocardial infarction.

Conventional electrocardiogram criteria for myocardial infarction (MI) rely on QRS features, but ST-T segment is also affected. We recorded body surface potential mapping in 24 patients with prior MI and in 24 controls. T-wave maximum amplitude and QRS and ST-T integrals were automatically determined. Old MI was verified by magnetic resonance imaging. ST-T integral and T-wave maximum amplitude outperformed QRS integral in detecting MI, with area under receiver operating characteristic curve of 94%, 95%, and 83%, respectively. ST-T integral performed better in non-Q-wave than Q-wave MI, with area under receiver operating characteristic curve of 97% and 92%, respectively. QRS integral correlated negatively with ST-T integral in patients with MI (r = -0.58, P < .001) and positively in controls (r = 0.45, P < .001). In conclusion, ST-T integral proved equal to QRS integral in old MI detection. Inclusion of ventricular repolarization phase and development of electrocardiographic analysis over larger chest area may improve the QRS-based diagnosis of old myocardial infarction.

Adult↗
PubMed2005

Calcium channel antagonism reduces exercise-induced ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia patients with RyR2 mutations.

UNLABELLED: Calcium channel antagonism in RyR2 defects. INTRODUCTION: Recently, gain-of-function mutations of cardiac ryanodine receptor RyR2 gene have been identified as a cause of familial or catecholaminergic polymorphic ventricular tachycardia. We examined the influence of the calcium channel blockers, verapamil and magnesium, on exercise-induced ventricular arrhythmias in patients with RyR2 mutations. METHODS AND RESULTS: Six molecularly defined catecholaminergic polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on beta-adrenergic blocker therapy, underwent exercise stress test four times: at baseline, after verapamil and magnesium sulphate infusions, and finally, without interventions. The number of isolated and successive premature ventricular complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at baseline, and was reduced during verapamil by 76+/-17% (P<0.05). Premature ventricular complexes appeared later and at higher heart rate during verapamil than at baseline (119+/-21 vs. 127+/-27 min-1, P<0.05). Magnesium did not inhibit the arrhythmias. Results in the fourth exercise stress test without interventions were similar to those in the first baseline study. CONCLUSIONS: This study provides the first in vivo demonstration that a calcium channel antagonist, verapamil, can suppress premature ventricular complexes and nonsustained ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium antagonists might have therapeutic value.

Calcium Channel Blockers↗
PubMed2005

Effects of epinephrine on right ventricular monophasic action potentials in the LQT1 versus LQT2 form of long QT syndrome: preferential enhancement of "triangulation" in LQT1.

AIMS: To explore effects of epinephrine and phenylephrine on the behavior of right ventricular monophasic action potentials (MAPs) in symptomatic LQT1 and LQT2 patients. METHODS AND RESULTS: We recorded endocardial MAPs from right interventricular septum at baseline and during epinephrine and phenylephrine infusions in six symptomatic DNA-verified LQT1 (QTc 528 +/- 83) and five LQT2 patients (QTc 527 +/- 72) and in five control patients (QTc 381 +/- 22). We measured MAP durations at 90% and at 50% levels of repolarization and their difference (MAP50 to MAP90, a measure of MAP morphologic "triangulation"), during atrial pacing to characterize rate dependence of MAPs and repolarization phase 3 durations, respectively. Restitution kinetics were determined during atrioventricular sequential pacing, using the approach of empirical restitution rate. Epinephrine prolonged MAP50-to-MAP90 duration and increased the rate dependence of MAP90 duration and increased restitution rate in type LQT1, but not in LQT2 patients nor in control subjects. Phenylephrine did not change MAP behavior. During epinephrine administration, both LQT1 and LQT2 patients had a ratio of the restitution rate of MAP to diastolic interval >1.0 at short diastolic intervals. CONCLUSION: Symptomatic LQT1 patients with prolonged baseline QTc intervals showed beta-adrenergic-induced changes in MAPs (triangulation) known to be arrhythmogenic, thus giving insight to the difference in clinical triggers of life-threatening arrhythmias between LQT1- and LQT2-affected individuals.

Action Potentials↗