M. Juhani Junttila

Long-term outcome associated with early repolarization on electrocardiography

BACKGROUND Early repolarization, which is characterized by an elevation of the QRS-ST junction (J point) in leads other than V(1) through V(3) on 12-lead electrocardiography, has been associated with vulnerability to ventricular fibrillation, but little is known about the prognostic significance of this pattern in the general population. METHODS We assessed the prevalence and prognostic significance of early repolarization on 12-lead electrocardiography in a community-based general population of 10,864 middle-aged subjects (mean [+/-SD] age, 44+/-8 years). The primary end point was death from cardiac causes, and secondary end points were death from any cause and death from arrhythmia during a mean follow-up of 30+/-11 years. Early repolarization was stratified according to the degree of J-point elevation (> or = 0.1 mV or > 0.2 mV) in either inferior or lateral leads. RESULTS The early-repolarization pattern of 0.1 mV or more was present in 630 subjects (5.8%): 384 (3.5%) in inferior leads and 262 (2.4%) in lateral leads, with elevations in both leads in 16 subjects (0.1%). J-point elevation of at least 0.1 mV in inferior leads was associated with an increased risk of death from cardiac causes (adjusted relative risk, 1.28; 95% confidence interval [CI], 1.04 to 1.59; P=0.03); 36 subjects (0.3%) with J-point elevation of more than 0.2 mV in inferior leads had a markedly elevated risk of death from cardiac causes (adjusted relative risk, 2.98; 95% CI, 1.85 to 4.92; P<0.001) and from arrhythmia (adjusted relative risk, 2.92; 95% CI, 1.45 to 5.89; P=0.01). Other electrocardiographic risk markers, such as a prolonged QT interval corrected for heart rate (P=0.03) and left ventricular hypertrophy (P=0.004), were weaker predictors of the primary end point. CONCLUSIONS An early-repolarization pattern in the inferior leads of a standard electrocardiogram is associated with an increased risk of death from cardiac causes in middle-aged subjects.

Early Repolarization Electrocardiographic Phenotypes Associated With Favorable Long-Term Outcome

Background— Early repolarization (ER) in inferior/lateral leads of standard ECGs increases the risk of arrhythmic death. We tested the hypothesis that variations in the ST-segment characteristics after the ER waveforms may have prognostic importance. Methods and Results— ST segments after ER were classified as horizontal/descending or rapidly ascending/upsloping on the basis of observations from 2 independent samples of young healthy athletes from Finland (n=62) and the United States (n=503), where ascending type was the dominant and common form of ER. Early repolarization was present in 27/62 (44%) of the Finnish athletes and 151/503 (30%) of the US athletes, and all but 1 of the Finnish (96%) and 91/107 (85%) of US athletes had an ascending/upsloping ST variant after ER. Subsequently, ECGs from a general population of 10 864 middle-aged subjects were analyzed to assess the prognostic modulation of ER-associated risk by ST-segment variations. Subjects with ER ≥0.1 mV and horizontal/descending ST variant (n=412) had an increased hazard ratio of arrhythmic death (relative risk 1.43; 95% confidence interval 1.05 to 1.94). When modeled for higher amplitude ER (>0.2 mV) in inferior leads and horizontal/descending ST-segment variant, the hazard ratio of arrhythmic death increased to 3.14 (95% confidence interval 1.56 to 6.30). However, in subjects with ascending ST variant, the relative risk for arrhythmic death was not increased (0.89; 95% confidence interval 0.52 to 1.55). Conclusions— ST-segment morphology variants associated with ER separates subjects with and without an increased risk of arrhythmic death in middle-aged subjects. Rapidly ascending ST segments after the J-point, the dominant ST pattern in healthy athletes, seems to be a benign variant of ER.Background— Early repolarization (ER) in inferior/lateral leads of standard ECGs increases the risk of arrhythmic death. We tested the hypothesis that variations in the ST-segment characteristics after the ER waveforms may have prognostic importance. Methods and Results— ST segments after ER were classified as horizontal/descending or rapidly ascending/upsloping on the basis of observations from 2 independent samples of young healthy athletes from Finland (n=62) and the United States (n=503), where ascending type was the dominant and common form of ER. Early repolarization was present in 27/62 (44%) of the Finnish athletes and 151/503 (30%) of the US athletes, and all but 1 of the Finnish (96%) and 91/107 (85%) of US athletes had an ascending/upsloping ST variant after ER. Subsequently, ECGs from a general population of 10 864 middle-aged subjects were analyzed to assess the prognostic modulation of ER-associated risk by ST-segment variations. Subjects with ER ≥0.1 mV and horizontal/descending ST variant (n=412) had an increased hazard ratio of arrhythmic death (relative risk 1.43; 95% confidence interval 1.05 to 1.94). When modeled for higher amplitude ER (>0.2 mV) in inferior leads and horizontal/descending ST-segment variant, the hazard ratio of arrhythmic death increased to 3.14 (95% confidence interval 1.56 to 6.30). However, in subjects with ascending ST variant, the relative risk for arrhythmic death was not increased (0.89; 95% confidence interval 0.52 to 1.55). Conclusions— ST-segment morphology variants associated with ER separates subjects with and without an increased risk of arrhythmic death in middle-aged subjects. Rapidly ascending ST segments after the J-point, the dominant ST pattern in healthy athletes, seems to be a benign variant of ER. # Clinical Perspective {#article-title-24}

Sudden Cardiac Death Caused by Coronary Heart Disease

An association between the anatomic pathology and pathophysiology of coronary atherosclerosis and sudden cardiac death (SCD) has been long recognized. At the end of the 15th century, Da Vinci described a personally witnessed SCD that he attributed to a “parched and shrunk and withered … artery that feeds the heart” at autopsy,1 and in 1812, Warren, commenting on the significance of Heberdens description of angina pectoris, reported a patient who died suddenly a short time after presenting with an anginal pattern of chest pain.2 However, insights into the magnitude and mechanisms of SCD as a consequence of the presence and extent of coronary atherosclerosis, its underlying vascular pathophysiology, the myocardial electrophysiology, and the role of ischemic cardiomyopathy began to unravel only during the past 50 years. Despite a rapidly developing base of knowledge about the tachyarrhythmic manifestations of acute coronary syndromes and chronic ischemic cardiomyopathy, especially during the past 25 years, that resulted from extensive clinical, investigative, and interventional advances, important challenges remain for the prediction and prevention of SCD caused by coronary heart disease (CHD).3 The total population burden of SCD resulting from CHD remains incompletely defined and debated.4 Estimates of the total number of SCDs annually in the United States are based largely on retrospective death certificate analyses,5,6 the American Heart Association statistical updates based on data from the National Center for Health Statistics,7 and nationwide extrapolations from well-studied community experiences.8,9 The most widely cited estimates have remained in the range of 300 000 to 350 000 SCDs annually since the early 1980s,10 suggesting an overall incidence between 1 and 2 deaths per 1000 person-years among the general population. However, estimates from the same death certificate sources range from 460 000 SCDs …

Induced Brugada-type electrocardiogram, a sign for imminent malignant arrhythmias.

Case presentation: A previously healthy 20-year-old man arrives at the emergency department for a consultation for mild fever. During his initial interview, he complains of palpitations to the triage nurse and therefore he undergoes an ECG, which is placed in the chart. A few minutes later, while awaiting his turn to be seen, he goes into cardiac arrest. The patient does not respond to resuscitation and dies in the emergency department. The autopsy reveals no cardiac structural abnormalities or evidence of myocarditis. The cause of death is determined as sudden unexplained cardiac death. The ECG from the emergency department revealed ST-segment elevation in the right precordial leads consistent with a Brugada ECG pattern. The Brugada syndrome is a heterogeneous genetic disease that predisposes to life-threatening ventricular tachyarrhythmias and sudden cardiac death (SCD). The syndrome is usually identified by a characteristic Brugada-type ECG that consists of ST elevation of a coved type in the precordial leads V1 to V3, although affected individuals may have a normal ECG.1,2 Because patients with Brugada syndrome usually become symptomatic at a relatively young age, early diagnosis is crucial to prevent SCD in those with a higher risk of developing an arrhythmic event.3 Approximately one fourth of the cases of Brugada syndrome are caused by loss of function mutations in the cardiac sodium channel SCN5A. Several nongenetic factors have been mentioned in the literature as possible inductors of the ECG pattern resembling Brugada syndrome.2 As such, a Brugada-type ECG may appear in some patients during febrile states …

Intraventricular Conduction Delay in a Standard 12-Lead Electrocardiogram as a Predictor of Mortality in the General Population

Background— Prolonged duration of QRS complex in a 12-lead ECG is associated with adverse prognosis in patients with cardiac disease, but its significance is not well established in the general population. In particular, there is a paucity of data on the prognostic significance of nonspecific intraventricular conduction delay in apparently healthy subjects. Methods and Results— We evaluated the 12-lead ECGs of 10 899 Finnish middle-aged subjects from the general population (52% of whom were men; mean age 44±8.5 years) between 1966 and 1972 and followed them for 30±11 years. Primary end points were all-cause mortality, cardiac mortality, and arrhythmic death. Prolonged QRS duration was defined as QRS ≥110 ms and intraventricular conduction delay as QRS ≥110 ms, without the criteria of complete or incomplete bundle-branch block. QRS duration ≥110 ms was present in 1.3% (n=147) and intraventricular conduction delay in 0.6% (n=67) of the subjects. Prolonged QRS duration predicted all-cause mortality (multivariate-adjusted relative risk [RR] 1.48; 95% confidence interval [CI] 1.22–1.81; P<0.001), cardiac mortality (RR 1.94; CI 1.44–2.63; P<0.001), and sudden arrhythmic death (RR 2.14; CI 1.38–3.33; P=0.002). Subjects with intraventricular conduction delay had increased all-cause mortality (RR 2.01; CI 1.52–2.66; P<0.001), increased cardiac mortality (RR 2.53; CI 1.64–3.90; P<0.001), and an elevated risk of arrhythmic death (RR 3.11; CI 1.74–5.54; P=0.001). Left bundle-branch block also weakly predicted arrhythmic death (P=0.04), but right bundle-branch block was not associated with increased mortality. Conclusions— Prolonged QRS duration in a standard 12-lead ECG is associated with increased mortality in a general population, with intraventricular conduction delay being most strongly associated with an increased risk of arrhythmic death.

Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).

Differences in 12‐Lead Electrocardiogram Between Symptomatic and Asymptomatic Brugada Syndrome Patients

Introduction: Brugada syndrome (BrS) is an inherited disorder that predisposes some subjects to sudden cardiac death (SCD). It is not well established which BrS patients are at risk of severe arrhythmias. Our aim was to study whether standard 12‐lead electrocardiogram (ECG) would give useful information for this purpose.

Association of Early Repolarization and Sudden Cardiac Death During an Acute Coronary Event

Background— Electrocardiographic early repolarization (ER) pattern has been previously associated with arrhythmic mortality and with an increased risk of ventricular fibrillation. We hypothesized that there is an association between ER and sudden cardiac death (SCD) during an acute coronary event. Methods and Results— The present study included 432 consecutive victims of SCD because of acute coronary event and 532 survivors of such an event, in whom 12-lead ECGs recorded before and unrelated to the event could be evaluated. SCDs were verified by medicolegal autopsy to be because of acute coronary event. ER was defined as an elevation of the QRS-ST junction in at least 2 inferior or lateral leads, manifested as QRS notching or slurring. The prevalence of ER pattern ≥0.1 mV was more common in cases (62/432; 14.4%) than controls (42/532; 7.9%) (P=0.001). The victims of SCD were younger, were more commonly men and smokers, had lower body mass index, had elevated heart rate, had prolonged QRS complex, and had lower prevalence of history of prior cardiovascular disease than controls. After adjustments for baseline differences, the odds ratio for J waves without ST-segment elevation in the SCD group was 2.15 (95% CI, 1.20–3.85; P=0.01). Conclusions— Higher prevalence of ER in a standard 12-lead ECG in victims of SCD than in survivors of an acute coronary event suggests that the presence of ER increases the vulnerability to fatal arrhythmia during acute myocardial ischemia and provides a plausible mechanistic link between this ECG pattern and higher arrhythmic mortality of middle-aged/elderly subjects.

QRS-T angle as a predictor of sudden cardiac death in a middle-aged general population

AIMS Spatial QRS-T angle measured from a 12-lead electrocardiogram (ECG) has been shown to predict cardiac mortality. However, there is a paucity of studies on the prognostic significance of frontal QRS-T angle, which is more readily available from the standard 12-lead ECG. The purpose of the present study was to investigate the importance of wide frontal QRS-T angle, QRS-axis, and T-wave axis as cardiac risk predictors in general population. METHODS AND RESULTS We evaluated the 12-lead ECGs of 10 957 Finnish middle-aged subjects from the general population recorded between 1966 and 1972, and followed them for 30 ± 11 years. QRS-T angle 0 to 90°, QRS-axis -30 to 90°, and T-wave axis 0 to 90° were considered normal. The primary endpoint was death from arrhythmia, and the secondary endpoints were all-cause mortality and non-arrhythmic cardiac mortality. QRS-T angle ≥ 100° was present in 2.0% of the subjects, and it was associated with an increased risk of sudden arrhythmic death [relative risk (RR) 2.26; 95% confidence interval (CI) 1.59-3.21; P< 0.001) and all-cause mortality (RR 1.57; CI 1.34-1.84; P< 0.001), but not with non-arrhythmic cardiac mortality (RR 1.34; CI 0.93-1.92; P= 0.13). The prognostic significance of wide QRS-T angle was mainly due to abnormal T-wave axis, which predicted death from arrhythmia (RR 2.13; CI 1.63-2.79; P< 0.001), all-cause mortality (RR 1.39; 1.24-1.55; P< 0.001), and non-arrhythmic cardiac death (RR 1.87; CI 1.50-2.34; P< 0.001). CONCLUSION Frontal QRS-T angle ≥ 100° increases the risk of arrhythmic death, this being mainly the result of an altered T-wave axis.

Causes of nonischemic sudden cardiac death in the current era

BACKGROUND Previous data have shown that various nonischemic cardiac diseases account for about 20% of sudden cardiac deaths (SCDs) and that dilated and hypertrophic cardiomyopathy (CM) are major causes of nonischemic SCD. OBJECTIVE The purpose of this study was to define the prevalence and causes of SCD due to nonischemic CM in the current era given the substantial change in the diagnosis and treatment of cardiac diseases and in lifestyle patterns. METHODS A total of 2661 consecutive victims of SCD from among a population of approximately 470,000 inhabitants in the Province of Oulu, Northern Finland, were included in the study. The causes of deaths were determined from the uniformly required autopsies of SCD victims in Finland, plus available medical records and standardized questionnaires. RESULTS Nonischemic cause of SCD was found in 579 victims (21.8% of all the SCDs). Mean age (± SD) was 55 (±12) years; 78% were males. After subgrouping the nonischemic SCDs into various categories, SCDs associated most closely with obesity (23.7%), followed by alcoholic CM (19.0%), hypertensive CM (15.5%), and fibrotic CM (13.6%). Fibrotic CM was the most common association with SCD in subjects younger than 40 years (28.3%), whereas alcoholic CM was the most common cause of death in subjects between 40 and 59 years of age (25.8%). CONCLUSION CM related to obesity, fibrotic CM, and alcoholic CM are commonly associated with nonischemic SCD in the current era. The association of SCD with fibrotic CM is notably frequent among victims younger than 40 years.