Clinical implications for affected parents and siblings of probands with long-QT syndrome.

BACKGROUND: Whenever a proband is identified with long-QT syndrome (LQTS), his or her parents and siblings should be evaluated regarding the possibility of carrying the disorder. In the majority of cases, one of the proband's parents and one or more siblings are affected. The aim of this study was (1) to determine whether the clinical severity of LQTS in the proband is useful in identifying first-degree family members at high risk for cardiac events, and (2) to evaluate the clinical course of affected parents and siblings of LQTS probands. METHODS AND RESULTS: The clinical and ECG characteristics of 211 LQTS probands and 791 first-degree relatives (422 parents and 369 siblings) were studied to determine if the clinical profile of the proband is useful in determining the clinical severity of LQTS in affected parents and siblings. Affected female parents of an LQTS proband had a greater cumulative risk for a first cardiac event than affected male parents. The probability of a parent or sibling having a first cardiac event was not significantly influenced by the severity of the proband's clinical symptoms. Female sex and QT(c) duration were risk factors for cardiac events among affected parents, and QT(c) was the only risk factor for cardiac events in affected siblings. CONCLUSIONS: The severity profile of LQTS in a proband was not found to be useful in identifying the clinical severity of LQTS in affected first-degree relatives of the proband.

Molecular pharmacology of the sodium channel mutation D1790G linked to the long-QT syndrome.

BACKGROUND: Multiple mutations of SCN5A, the gene that encodes the human Na(+) channel alpha-subunit, are linked to 1 form of the congenital long-QT syndrome (LQT-3). D1790G (DG), an LQT-3 mutation of the C-terminal region of the Na(+) channel alpha-subunit, alters steady-state inactivation of expressed channels but does not promote sustained Na(+) channel activity. Recently, flecainide, but not lidocaine, has been found to correct the disease phenotype, delayed ventricular repolarization, in DG carriers. METHODS AND RESULTS: To understand the molecular basis of this difference, we studied both drugs using wild-type (WT) and mutant Na(+) channels expressed in HEK 293 cells. The DG mutation conferred a higher sensitivity to lidocaine (EC(50), WT=894 and DG=205 micromol/L) but not flecainide tonic block in a concentration range that is not clinically relevant. In contrast, in a concentration range that is therapeutically relevant, DG channels are blocked selectively by flecainide (EC(50), WT=11.0 and DG=1.7 micromol/L), but not lidocaine (EC(50), WT=318.0 and DG=176 micromol/L) during repetitive stimulation. CONCLUSIONS: These results (1) demonstrate that the DG mutation confers a unique pharmacological response on expressed channels; (2) suggest that flecainide use-dependent block of DG channels underlies its therapeutic effects in carriers of this gene mutation; and (3) suggest a role of the Na(+) channel alpha-subunit C-terminus in the flecainide/channel interaction.

Arrhythmogenic mechanism of an LQT-3 mutation of the human heart Na(+) channel alpha-subunit: A computational analysis.

BACKGROUND: D1790G, a mutation of SCN5A, the gene that encodes the human Na(+) channel alpha-subunit, is linked to 1 form of the congenital long-QT syndrome (LQT-3). In contrast to other LQT-3-linked SCN5A mutations, D1790G does not promote sustained Na(+) channel activity but instead alters the kinetics and voltage-dependence of the inactivated state. METHODS AND RESULTS: We modeled the cardiac ventricular action potential (AP) using parameters and techniques described by Luo and Rudy as our control. On this background, we modified only the properties of the voltage-gated Na(+) channel according to our patch-clamp analysis of D1790G channels. Our results indicate that D1790G-induced changes in Na(+) channel activity prolong APs in a steeply heart rate-dependent manner not directly due to changes in Na(+) entry through mutant channels but instead to alterations in the balance of net plateau currents by modulation of calcium-sensitive exchange and ion channel currents. CONCLUSIONS: We conclude that the D1790G mutation of the Na(+) channel alpha-subunit can prolong the cardiac ventricular AP despite the absence of mutation-induced sustained Na(+) channel current. This prolongation is calcium-dependent, is enhanced at slow heart rates, and at sufficiently slow heart rate triggers arrhythmogenic early afterdepolarizations.

Effects of flecainide in patients with new SCN5A mutation: mutation-specific therapy for long-QT syndrome?

BACKGROUND: Mutations in the cardiac sodium channel gene (SCN5A) can cause one variant of the congenital long-QT syndrome. The effects of some of these mutations on the alpha-subunit channel properties can be blocked by type Ib antiarrhythmic drugs. Recently, we have described a new SCN5A mutation (D1790G) that affects the channel properties in a manner suggesting that sodium blockers of the Ib type will be ineffective in carriers of this mutation. Hence, the ECG effects of flecainide-acetate, a type Ic sodium blocker, were evaluated in carriers of this mutation. METHODS AND RESULTS: Eight asymptomatic mutation carriers and 5 control subjects were studied. Intravenous lidocaine was tested first in only 2 mutation carriers and had no significant effect on any ECG parameter. Flecainide significantly shortened all heart rate-corrected repolarization duration parameters only in carriers and not in control subjects: QT(c) shortened by 9.5% (from 517+/-45 to 468+/-36 ms, P=0.011), and the S-offset to T-onset interval shortened by 64.7% (from 187+/-88 to 66+/-50 ms, P=0.0092). Flecainide also normalized the marked baseline repolarization dispersion in most mutation carriers. These effects among carriers were maintained during long-term (9 to 17 months) outpatient flecainide therapy with no adverse effects. CONCLUSIONS: This report is the first to describe SCN5A mutation carriers who significantly responded to flecainide therapy yet did not respond to lidocaine. These results have important implications for long-QT allele-specific therapeutic strategies.

Clinical and genetic variables associated with acute arousal and nonarousal-related cardiac events among subjects with long QT syndrome.

In patients with the long QT syndrome (LQTS), the occurrence of cardiac events (syncope or cardiac arrest) is frequently associated with acute arousal caused by exercise, swimming, emotion, or noise. However, cardiac events may also occur during sleep or with ordinary daily activities. The purpose of this study was to determine whether there are differential clinical, electrocardiographic, and genetic features among LQTS patients who experienced cardiac events with and without acute arousal. We identified 1,325 patients with cardiac events from the International LQTS Registry. Based on the precipitating conditions of the first event, 427 patients were classified as arousal, 345 as nonarousal, and the remaining 553 were unknown (not classifiable). Gene linkage was known in 78 of the 772 patients with classifiable first events. The age at first cardiac event was significantly younger in the arousal than the nonarousal group (11.7 vs. 15.5 years, respectively; p<0.001). The arousal-type patients had a higher rate of subsequent cardiac events during follow-up after the index event than the nonarousal-type patients (p = 0.02). Arousal-related cardiac events occurred in 85% of LQT1, 67% of LQT2, and 33% of LQT3 patients (p = 0.008). This study provides evidence that the genotype is an important determinant of the LQTS phenotype in terms of arousal and nonarousal-related cardiac events.

Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome.

BACKGROUND: beta-blockers are routinely prescribed in congenital long-QT syndrome (LQTS), but the effectiveness and limitations of beta-blockers in this disorder have not been evaluated. METHODS AND RESULTS: The study population comprised 869 LQTS patients treated with beta-blockers. Effectiveness of beta-blockers was analyzed during matched periods before and after starting beta-blocker therapy, and by survivorship methods to determine factors associated with cardiac events while on prescribed beta-blockers. After initiation of beta-blockers, there was a significant (P<0.001) reduction in the rate of cardiac events in probands (0.97+/-1.42 to 0.31+/-0.86 events per year) and in affected family members (0. 26+/-0.84 to 0.15+/-0.69 events per year) during 5-year matched periods. On-therapy survivorship analyses revealed that patients with cardiac symptoms before beta-blockers (n=598) had a hazard ratio of 5.8 (95% CI, 3.7 to 9.1) for recurrent cardiac events (syncope, aborted cardiac arrest, or death) during beta-blocker therapy compared with asymptomatic patients; 32% of these symptomatic patients will have another cardiac event within 5 years while on prescribed beta-blockers. Patients with a history of aborted cardiac arrest before starting beta-blockers (n=113) had a hazard ratio of 12.9 (95% CI, 4.7 to 35.5) for aborted cardiac arrest or death while on prescribed beta-blockers compared with asymptomatic patients; 14% of these patients will have another arrest (aborted or fatal) within 5 years on beta-blockers. CONCLUSIONS: beta-blockers are associated with a significant reduction in cardiac events in LQTS patients. However, syncope, aborted cardiac arrest, and LQTS-related death continue to occur while patients are on prescribed beta-blockers, particularly in those who were symptomatic before starting this therapy.

Spectrum of ST-T-wave patterns and repolarization parameters in congenital long-QT syndrome: ECG findings identify genotypes.

BACKGROUND: Congenital long-QT syndrome (LQTS) is caused by mutations of genes encoding the slow component of the delayed rectifier current (LQT1, LQT5), the rapid component of the delayed rectifier current (LQT2, LQT6), or the Na(+) current (LQT3), resulting in ST-T-wave abnormalities on the ECG. This study evaluated the spectrum of ST-T-wave patterns and repolarization parameters by genotype and determined whether genotype could be identified by ECG. METHODS AND RESULTS: ECGs of 284 gene carriers were studied to determine ST-T-wave patterns, and repolarization parameters were quantified. Genotypes were identified by individual ECG versus family-grouped ECG analysis in separate studies using ECGs of 146 gene carriers from 29 families and 233 members of 127 families undergoing molecular genotyping, respectively. Ten typical ST-T patterns (4 LQT1, 4 LQT2, and 2 LQT3) were present in 88% of LQT1 and LQT2 carriers and in 65% of LQT3 carriers. Repolarization parameters also differed by genotype. A combination of quantified repolarization parameters identified genotype with sensitivity/specificity of 85%/70% for LQT1, 83%/94% for LQT2, and 47%/63% for LQT3. Typical patterns in family-grouped ECGs best identified the genotype, being correct in 56 of 56 (21 LQT1, 33 LQT2, and 2 LQT3) families with mutation results. CONCLUSIONS: Typical ST-T-wave patterns are present in the majority of genotyped LQTS patients and can be used to identify LQT1, LQT2, and possibly LQT3 genotypes. Family-grouped ECG analysis improves genotype identification accuracy. This approach can simplify genetic screening by targeting the gene for initial study. The multiple ST-T patterns in each genotype raise questions regarding the pathophysiology and regulation of repolarization in LQTS.

Asthma and the risk of cardiac events in the Long QT syndrome. Long QT Syndrome Investigative Group.

While acquiring data for the International Long QT Syndrome Registry, we noticed that a number of patients referred for long QT syndrome (LQTS) were affected by asthma. The effect of asthma comorbidity on clinical course of LQTS has not been studied. This study aimed to evaluate the prevalence of asthma in patients with LQTS, determine the influence of asthma comorbidity on outcome of LQTS patients, and to investigate the confounding effects of beta mimetics and beta blockers on the occurrence of cardiac events in asthmatic patients. The influence of asthma on risk of cardiac events (syncope, aborted cardiac arrest, or LQTS death) was evaluated after accounting for age, gender, QTc, and RR interval duration, beta-blocker and beta-mimetic use. Asthma was identified in 226 (5.2%) of 4,310 studied LQTS family members. Longer QTc duration was associated with higher incidence of asthma (p <0.001). Asthma was independently associated with significantly increased risk of cardiac events in affected LQTS patients (hazard ratio 1.32; p = 0.048) and in borderline-affected family members (hazard ratio 2.08; p = 0.004) after adjustment for QTc, RR interval, and gender. An increased risk of cardiac events in asthmatic patients observed before beta-blocker therapy was reduced after initiation of treatment with beta blockers. In conclusion, the occurrence of asthma in LQTS patients increases with QTc duration. Asthma comorbidity in LQTS patients is associated with an increased risk of cardiac events. The asthma-associated increase in the risk of LQTS-related cardiac events is diminished after initiation of beta-blocker therapy, suggesting a possible role of beta-receptor modulation underlying asthma-LQTS association.

Comparison of clinical and genetic variables of cardiac events associated with loud noise versus swimming among subjects with the long QT syndrome.

Acute auditory stimuli and swimming activities are frequently associated with syncope, aborted cardiac arrest, and death in the long QT syndrome (LQTS). We investigated the clinical and genetic findings associated with cardiac events precipitated by these arousal factors. The study population involved 195 patients with an index cardiac event associated with a loud noise (n = 77) or swimming activity (n = 118). Patients with events associated with loud auditory stimuli were older at their index event and were more likely to be women than patients who experienced events during swimming-related activities. Patients with an index event associated with loud noise were likely to have subsequent events related to auditory stimuli; patients with an index event associated with swimming were likely to have recurrent events related to swimming or physical activities. Family patterning of auditory and swimming and/or physical activity-related events was evident. Genotype analyses in 25 patients revealed a significant difference in the distribution of index cardiac events by genotype (p <0.001), with all 19 patients with swimming-related episodes associated with LQT1 genotype and 5 of 6 patients with auditory-related events associated with LQT2 genotype. The clinical profile and genotype findings of patients with LQTS who experience cardiac events related to acute auditory stimuli are quite different from those who experience events accompanying swimming activities.

[Use of abciximab (Reopro) in the catheterization laboratory and in unstable coronary syndromes].

Blockage of platelet glycoprotein IIb/IIIa receptor by Reopro (c7E3 Fab-abciximab) has been shown to reduce markedly ischemic complications during and following elective and high-risk coronary intervention (CI). Between July '96 and February '98, 120 consecutive patients (85 men and 34 women, aged 34-90--mean 62) received Reopro (20 mg bolus, followed by 10 micrograms/min for 12-48 hours). 100 were treated with Reopro in the catheterization laboratory, in 76 as prophylactic treatment preceding high-risk CI and in 24 as bailout treatment for acute complications during CI. 20 additional patients were treated in the CCU for acute coronary syndromes, 17 of whom underwent CI 6-48 hours later. Coronary angiography demonstrated multivessel disease in 66 (56%), and the target lesions were LAD--77, RCA--41, LCX--22, SVG--6, and 2 unprotected LMCA (total: 148 lesions dilated in 117 patients). Of the 117 CI, 44 were PTCA alone, and 73 included stenting. Indications for prophylactic Reopro for high risk CI were: acute MI (< or = 48 hours), early post-MI angina, unstable AP, and/or complex anatomy with visible thrombus. In this high-risk population the overall success rate (open artery, no MI, discharged alive, no need for urgent re-vascularization) was 97% when Reopro was given prophylactically prior to CI. The success rate was lower (87.5%) when Reopro was given in bailout situations. In 20 patients with acute coronary syndromes treated in the CCU while receiving maximal combined conventional therapy (including full-dose heparin), all symptoms and dynamic ischemic ECG changes disappeared within minutes following Reopro. 17 underwent successful CI during hospitalization and 3 were treated medically. Reopro given prior to high risk CI was associated with a very low rate of complications. In a few cases with acute coronary syndromes, Reopro given in the CCU cases immediate relief of myocardial ischemia and reduced the need for urgent coronary intervention.

Influence of the genotype on the clinical course of the long-QT syndrome. International Long-QT Syndrome Registry Research Group.

BACKGROUND: The congenital long-QT syndrome, caused by mutations in cardiac potassium-channel genes (KVLQT1 at the LQT1 locus and HERG at the LQT2 locus) and the sodium-channel gene (SCN5A at the LQT3 locus), has distinct repolarization patterns on electrocardiography, but it is not known whether the genotype influences the clinical course of the disease. METHODS: We determined the genotypes of 541 of 1378 members of 38 families enrolled in the International Long-QT Syndrome Registry: 112 had mutations at the LQT1 locus, 72 had mutations at the LQT2 locus, and 62 had mutations at the LQT3 locus. We determined the cumulative probability and lethality of cardiac events (syncope, aborted cardiac arrest, or sudden death) occurring from birth through the age of 40 years according to genotype in the 246 gene carriers and in all 1378 members of the families studied. RESULTS: The frequency of cardiac events was higher among subjects with mutations at the LQT1 locus (63 percent) or the LQT2 locus (46 percent) than among subjects with mutations at the LQT3 locus (18 percent) (P<0.001 for the comparison of all three groups). In a multivariate Cox analysis, the genotype and the QT interval corrected for heart rate were significant independent predictors of a first cardiac event. The cumulative mortality through the age of 40 among members of the three groups of families studied was similar; however, the likelihood of dying during a cardiac event was significantly higher (P<0.001) among families with mutations at the LQT3 locus (20 percent) than among those with mutations at the LQT1 locus (4 percent) or the LQT2 locus (4 percent). CONCLUSIONS: The genotype of the long-QT syndrome influences the clinical course. The risk of cardiac events is significantly higher among subjects with mutations at the LQT1 or LQT2 locus than among those with mutations at the LQT3 locus. Although cumulative mortality is similar regardless of the genotype, the percentage of cardiac events that are lethal is significantly higher in families with mutations at the LQT3 locus.

Novel LQT-3 mutation affects Na+ channel activity through interactions between alpha- and beta1-subunits.

The congenital long-QT syndrome (LQT), an inherited cardiac arrhythmia characterized in part by prolonged ventricular repolarization, has been linked to 5 loci, 4 of which have been shown to harbor genes that encode ion channels. Previously studied LQT-3 mutations of SCN5A (or hH1), the gene that encodes the human Na+ channel alpha-subunit, have been shown to encode voltage-gated Na+ channels that reopen during prolonged depolarization and hence directly contribute to the disease phenotype: delayed repolarization. Here, we report the functional consequences of a novel SCN5A mutation discovered in an extended LQT family. The mutation, a single A-->G base substitution at nucleotide 5519 of the SCN5A cDNA, is expected to cause a nonconservative change from an aspartate to a glycine at position 1790 (D1790G) of the SCN5A gene product. We investigated ion channel activity in human embryonic kidney (HEK 293) cells transiently transfected with wild-type (hH1) or mutant (D1790G) cDNA alone or in combination with cDNA encoding the human Na+ channel beta1-subunit (hbeta1) using whole-cell patch-clamp procedures. Heteromeric channels formed by coexpression of alpha- and beta1-subunits are affected: steady-state inactivation is shifted by -16 mV, but there is no D1790G-induced sustained inward current. This effect is independent of the beta1-subunit isoform. We find no significant effect of D1790G on the biophysical properties of monomeric alpha- (hH1) channels. We conclude that the effects of the novel LQT-3 mutation on inactivation of heteromeric channels are due to D1790G-induced changes in alpha- and beta1-interactions.

Identification of a new SCN5A mutation, D1840G, associated with the long QT syndrome. Mutations in brief no. 153. Online.

The long QT syndrome (LQT) is an inherited cardiac disorder that can cause sudden cardiac death among apparently healthy young individuals due to malignant ventricular arrhythmias. LQT was found to be caused by mutations in four genes LTQ1, LQT2, LQT3 and LQT5, and linkage was reported for an additional locus, LQT4, on chromosome 4q25-27. We have studied a large (n=131) LQT-affected Jewish kindred and identified tight linkage between the LQT-affected status and LQT3 (lod score 6.13, with an estimated recombination fraction of zero). We identified a new point-mutation, A to G substitution at nucleotide 5519 of the SCN5A gene, changing the aspartate 1840 to glycine, D1840G. This is a non-conservative change of an amino acid completely conserved in sodium channels from Molusca to human. The mutation was identified in all affected individuals (n=23), and not identified in all the unaffected family members (n=40), and not in 200 chromosomes of healthy control individuals. The mutation was identified in 3/12 individuals with equivocal phenotype, thus, providing an accurate dignostic tool for all family members. This mutation is currently being used in a cellular electrophysiological model, to characterize the function of the mutated sodium channel in this syndrome.

Detection and significance of myocardial ischemia in women versus men within six months of acute myocardial infarction or unstable angina. The Multicenter Myocardial Ischemia Research Group.

Ischemia detection after an acute coronary event predicts subsequent cardiac events. However, gender-related aspects in the prevalence and prognostic significance of ischemia detection after an acute coronary event have not been reported. Noninvasive tests, which included resting 12-lead electrocardiogram (ECG), 24-hour ambulatory ECG, exercise ECG, and thallium-201 stress scintigraphy were performed in 936 stable patients (224 women and 712 men) 1 to 6 months (average 2.7) after an acute coronary event (i.e., myocardial infarction or unstable angina). Primary end points during an average follow-up of 23 months included cardiac death, nonfatal myocardial infarction, and unstable angina, while restricted end points included the first 2. Ischemia detection was significantly less frequent among women than among men on 24-hour ambulatory ECG, exercise ECG, and thallium-201 stress scintigraphy. Primary end points occurred in 19.2% of women and in 19% of men, and restricted end points occurred in 5.8% of women versus 8%. of men (p = NS). Cox analyses revealed that gender and its interaction with each of the ischemia tests did not contribute to the prediction of the primary or restricted end points. We conclude that in stable patients 1 to 6 months after an acute coronary event, ischemia detection by noninvasive tests was significantly less prevalent in women than in men. However, subsequent cardiac event rates in women were similar to those observed in men, and there was no gender-ischemic detection interaction regarding subsequent events.

ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome.

BACKGROUND: The long QT syndrome is an inherited disorder with prolonged ventricular repolarization and a propensity to ventricular tachyarrhythmias and sudden arrhythmic death. Recent linkage studies have demonstrated three separate loci for this disorder on chromosomes 3, 7, and 11, and specific mutated genes for long QT syndrome have been identified on two of these chromosomes. We investigated ECG T-wave patterns (phenotypes) in members of families linked to three genetically distinct forms of the long QT syndrome. METHODS AND RESULTS: Five quantitative ECG repolarization parameters, ie, four Bazett-corrected time intervals (QTonset-c, QTpeak-c, QTc, and Tduration-c, in milliseconds) and the absolute height of the T wave (Tamplitude, in millivolts), were measured in 153 members of six families with long QT syndrome linked to markers on chromosomes 3 (n = 47), 7 (n = 30), and 11 (n = 76). Genotypic data were used to define each family member as being affected or unaffected with long QT syndrome. Affected members of all six families had longer QT intervals (QTonset-c, QTpeak-c, or QTc) than unaffected family members (P < .01). Each of the three long QT syndrome genotypes was associated with somewhat distinctive ECG repolarization features. Among affected individuals, the QTonset-c was unusually prolonged in those individuals with mutations involving the cardiac sodium channel gene SCN5A on chromosome 3 (lead II QTonset-c [mean +/- SD]: chromosome 3, 341 +/- 42 ms; chromosome 7, 290 +/- 56 ms; chromosome 11, 243 +/- 73 ms; P < .001); Tamplitude was generally quite small in the chromosome 7 genotype (lead II Tamplitude, mV: chromosome 3, 0.36 +/- 0.14; chromosome 7, 0.13 +/- 0.07; chromosome 11, 0.37 +/- 0.17; P < .001); and Tduration was particularly long in the chromosome 11 genotype (lead II Tduration-c: chromosome 3, 187 +/- 33 ms; chromosome 7, 191 +/- 51 ms; chromosome 11, 262 +/- 65 ms; P < .001). Similar ECG findings were observed in leads aVF and V5. A considerable variability exists in the quantitative repolarization parameters associated with each genotype, with overlap in the T-wave patterns among the three genotypes. CONCLUSIONS: Three separate genetic loci for the long QT syndrome including mutations in two cardiac ionic channel genes were associated with different phenotypic T-wave patterns on the ECG. This study provides insight into the influence of genetic factors on ECG manifestations of ventricular repolarization.

Comparison of early invasive and conservative treatments in patients with anterior wall non-Q-wave acute myocardial infarction.

To compare the long-term prognosis of a group of patients treated by an early invasive approach after a non-Q-wave anterior wall acute myocardial infarction (AMI) with a similar group treated conservatively, data from 110 consecutive patients with non-Q-wave AMI were retrospectively obtained from 3 different hospitals: (1) a hospital with coronary angioplasty and coronary bypass facilities favoring on early invasive approach, (2) a hospital with a catheterization laboratory and no coronary angioplasty or coronary bypass facilities, and (3) a community hospital without a catheterization laboratory. Patients were divided according to the presence or absence of an early invasive approach: those who had undergone in-hospital catheterization and revascularization (n = 55) and those with a conservative approach (n = 55). The early invasive approach resulted in a significant decrease in major events. The rate of recurrent myocardial infarction was 29% in the conservative group versus 7.2% in the invasive group (p = 0.025). Survival rate curves at 3-year follow-up showed significant differences in mortality (p = 0.001), recurrent myocardial infarction (p = 0.002), recurrent angina pectoris (p = 0.001), and development of congestive heart failure (p = 0.05). Multivariate analysis disclosed the early invasive approach to be an independent predictor for decreasing the likelihood of recurrent infarction by 86% (odds ratio 0.14, confidence intervals 0.04 to 0.48, p = 0.0006), and for decreasing the likelihood of recurrent angina by 66% (odds ratio 0.34, confidence intervals 0.18 to 0.63, p < 0.005). The early invasive strategy may result in an improved outcome in the treatment of patients with non-Q-wave anterior wall AMI compared with patients treated conservatively.