Tuomas Kenttä

Early repolarization as a predictor of arrhythmic and nonarrhythmic cardiac events in middle-aged subjects

BACKGROUND Early repolarization (ER) in the inferior/lateral leads predicts mortality, but whether ER is a specific sign of increased risk for arrhythmic events is not known. OBJECTIVE The purpose of this study was to study the association of ER and arrhythmic events and nonarrhythmic morbidity and mortality. METHODS We assessed the prognostic significance of ER in a community-based general population of 10,846 middle-aged subjects (mean age 44 ± 8 years). The end-points were sustained ventricular tachycardia or resuscitated ventricular fibrillation (VT-VF), arrhythmic death, nonarrhythmic cardiac death, new-onset atrial fibrillation (AF), hospitalization for congestive heart failure, or coronary artery disease during mean follow-up of 30 ± 11 years. ER was defined as ≥0.1-mV elevation of J point in either inferior or lateral leads. RESULTS After including all risk factors of cardiac mortality and morbidity in Cox regression analysis, inferior ER (prevalence 3.5%) predicted VF-VT events (n = 108 [1.0%]) with a hazard ratio (HR) of 2.2 (95% confidence interval [CI] 1.1-4.5, P = .03) but not nonarrhythmic cardiac death (n = 1235 [12.2%]), AF (n = 1659 [15.2%]), congestive heart failure (n = 1752 [16.1%]), or coronary artery disease (n = 3592 [32.9%]) (P = NS for all). Inferior ER predicted arrhythmic death in cases without other QRS complex abnormalities (multivariate HR 1.68, 95 % CI 1.10-2.58, P = .02) but not in those with ER and other coexisting abnormalities in QRS morphology (HR 1.30, 95% CI 0.86-1.96, P = .22). CONCLUSION ER in the inferior leads, especially in cases without other QRS complex abnormalities, predicts the occurrence of VT-VF but not nonarrhythmic cardiac events, suggesting that ER is a specific sign of increased vulnerability to ventricular tachyarrhythmias.

Prevalence and Prognostic Significance of Abnormal P Terminal Force in Lead V1 of the ECG in the General Population

Background—Prevalence and prognostic significance of abnormal P terminal force (PTF) in the general population are not known. The aim of this study was to assess the prevalence of abnormal PTF and to compare clinical outcomes of middle-aged subjects with and without the PTF. Methods and Results—The presence of PTF was assessed in a cohort of 10 647 middle-aged subjects (mean age [SD], 44 [8] years; 47.2% female). The subjects were followed 35 to 41 years, and data on mortality and hospitalizations were obtained from national registers. Primary outcomes were all-cause mortality, cardiac mortality, and arrhythmic death. Secondary outcomes were hospitalization because of congestive heart failure, coronary heart disease, new onset atrial fibrillation, and stroke. The Cox proportional hazards model was used to assess the risk for death (all-cause), and the Fine and Gray competing risks model was used for other outcomes. The prevalence of PTF 0.04 to 0.049, 0.05 to 0.059, and ≥0.06 mm·s were 4.8%, 1.5%, and 1.2%, respectively. Subjects presenting PTF ≥0.04 mm·s were at increased risk for death, cardiac death, and congestive heart failure, and subjects presenting PTF ≥0.06 mm·s were at increased risk for atrial fibrillation. However, after adjustment for potential confounding factors, an increased risk was observed only for death (hazard ratio, 1.76; 95% confidence interval, 1.45–2.12; P<0.001) and atrial fibrillation (hazard ratio, 1.91; 95% confidence interval, 1.34–2.73; P<0.001) in subjects presenting PTF ≥0.06 mm·s. Conclusions—PTF ≥0.04 mm·s is a relatively common finding in a 12-lead ECG of middle-aged subjects. PTF ≥0.06 mm·s is associated with increased risk for atrial fibrillation and death in the general population.

Prediction of sudden cardiac death with automated high-throughput analysis of heterogeneity in standard resting 12-lead electrocardiograms

BACKGROUND Heterogeneity of depolarization and repolarization underlies the development of lethal arrhythmias. OBJECTIVE We investigated whether quantification of spatial depolarization and repolarization heterogeneity identifies individuals at risk for sudden cardiac death (SCD). METHODS Spatial R-, J-, and T-wave heterogeneity (RWH, JWH, and TWH, respectively) was analyzed using automated second central moment analysis of standard digital 12-lead electrocardiograms in 5618 adults (2588, 46% men; mean ± SEM age 50.9 ± 0.2 years), who took part in the epidemiological Health 2000 Survey as representative of the entire Finnish adult population. RESULTS During the follow-up period of 7.7 ± 0.2 years, a total of 72 SCDs occurred (1.3%), with an average yearly incidence rate of 0.17% per year. Increased RWH, JWH, and TWH in left precordial leads (V4-V6) were univariately associated with SCD (P < .001 for each). When adjusted with standard clinical risk markers, JWH and TWH remained independent predictors of SCD. Increased TWH (≥102 µV) was associated with a 1.7-fold adjusted relative risk for SCD (95% confidence interval [CI] 1.0-2.9; P = .048) and increased JWH (≥123 µV) with a 2.0-fold adjusted relative risk for SCD (95% CI 1.2-3.3; P = .006). When both TWH and JWH were above the threshold, the adjusted relative risk for SCD was 2.9-fold (95% CI 1.5-5.7; P = .002). When RWH (≥470 µV), JWH, and TWH were all above the threshold, the adjusted relative risk for SCD was 3.2-fold (95% CI 1.4-7.1; P = .009). CONCLUSION Second central moment analysis of standard resting 12-lead electrocardiographic morphology provides an ultrarapid means for the automated measurement of spatial RWH, JWH, and TWH, enabling analysis of high subject volumes and screening for SCD risk in the general population.

Prevalence and Prognostic Significance of Abnormal P Terminal Force in Lead V1 of the Electrocardiogram in the General Population

Background—Prevalence and prognostic significance of abnormal P terminal force (PTF) in the general population are not known. The aim of this study was to assess the prevalence of abnormal PTF and to compare clinical outcomes of middle-aged subjects with and without the PTF. Methods and Results—The presence of PTF was assessed in a cohort of 10 647 middle-aged subjects (mean age [SD], 44 [8] years; 47.2% female). The subjects were followed 35 to 41 years, and data on mortality and hospitalizations were obtained from national registers. Primary outcomes were all-cause mortality, cardiac mortality, and arrhythmic death. Secondary outcomes were hospitalization because of congestive heart failure, coronary heart disease, new onset atrial fibrillation, and stroke. The Cox proportional hazards model was used to assess the risk for death (all-cause), and the Fine and Gray competing risks model was used for other outcomes. The prevalence of PTF 0.04 to 0.049, 0.05 to 0.059, and ≥0.06 mm·s were 4.8%, 1.5%, and 1.2%, respectively. Subjects presenting PTF ≥0.04 mm·s were at increased risk for death, cardiac death, and congestive heart failure, and subjects presenting PTF ≥0.06 mm·s were at increased risk for atrial fibrillation. However, after adjustment for potential confounding factors, an increased risk was observed only for death (hazard ratio, 1.76; 95% confidence interval, 1.45–2.12; P<0.001) and atrial fibrillation (hazard ratio, 1.91; 95% confidence interval, 1.34–2.73; P<0.001) in subjects presenting PTF ≥0.06 mm·s. Conclusions—PTF ≥0.04 mm·s is a relatively common finding in a 12-lead ECG of middle-aged subjects. PTF ≥0.06 mm·s is associated with increased risk for atrial fibrillation and death in the general population.

QRS-T morphology measured from exercise electrocardiogram as a predictor of cardiac mortality

AIMS Total cosine R-to-T (TCRT) measured from the standard 12-lead electrocardiogram (ECG) reflects the spatial relationship between depolarization and repolarization wavefronts and a low TCRT value is a marker of poor prognosis. We tested the hypothesis that measurement of TCRT or QRS/T angle from exercise ECG would provide even more powerful prognostic information. METHODS AND RESULTS The prognostic significances of TCRT and QRS/T angle were assessed from exercise ECG recordings in 1297 patients [age 56 ± 13 years (mean ± SD), 67% males] undergoing a clinically indicated bicycle stress-test and the subsequent follow-up. During an average follow-up of 45 ± 12 months, 74 patients died (5.7%); 34 (2.6%) were cardiac deaths, and 24 (1.9%) were sudden cardiac deaths. Total cosine R-to-T and QRS/T angle exhibited a correlation with the RR intervals in the total cohort, but the individual responses were variable, e.g. median correlation of TCRT-RR was 0.89 with an inter-quartile range from 0.55 to 0.98. A reduced correlation of TCRT-RR during the recovery phase of exercise ECG predicted cardiac death [adjusted heart rate (HR) 3.5, 95% confidence interval (CI): 1.8-6.8, P= 0.001] similarly as the baseline TCRT measured from ECG at rest (adjusted HR 3.4, 95% CI: 1.4-8.1, P= 0.01). The poor correlation between the TCRT-RR both during the exercise and recovery was specifically related to a risk of sudden cardiac death (adjusted HR 6.2, 95% CI: 2.1-17.8, P< 0.001). CONCLUSIONS Loss of rate-adaptation of the spatial relationship between depolarization and repolarization wavefronts is a strong predictor of cardiac death, especially of sudden cardiac death.

Relationship Between Testosterone Level and Early Repolarization on 12-Lead Electrocardiograms in Men

To the Editor: An inferolateral early repolarization (ER) electrocardiographic (ECG) pattern has been associated with an increased risk of sudden cardiac death [(1–4)][1]. A strong male predominance in the prevalence of an ER ECG pattern has been observed, with a higher prevalence in young men [(

Dynamics and Rate‐Dependence of the Spatial Angle between Ventricular Depolarization and Repolarization Wave Fronts during Exercise ECG

Background: QRS/T angle and the cosine of the angle between QRS and T‐wave vectors (TCRT), measured from standard 12‐lead electrocardiogram (ECG), have been used in risk stratification of patients. This study assessed the possible rate dependence of these variables during exercise ECG in healthy subjects.

Cardiac Repolarization and Autonomic Regulation during Short-Term Cold Exposure in Hypertensive Men: An Experimental Study

Objectives The aim of our study was to assess the effect of short-term cold exposure, typical in subarctic climate, on cardiac electrical function among untreated middle-aged hypertensive men. Methods We conducted a population-based recruitment of 51 hypertensive men and a control group of 32 men without hypertension (age 55–65 years) who underwent whole-body cold exposure (15 min exposure to temperature −10°C, wind 3 m/s, winter clothes). Conduction times and amplitudes, vectorcardiography, arrhythmias, and heart rate variability (autonomic nervous function) were assessed. Results Short-term cold exposure increased T-peak to T-end interval from 67 to 72 ms (p<0.001) and 71 to 75 ms (p<0.001) and T-wave amplitude from 0.12 to 0.14 mV (p<0.001) and from 0.17 to 0.21 mV (p<0.001), while QTc interval was shortened from 408 to 398 ms (p<0.001) and from 410 to 401 ms (p<0.001) among hypertensive men and controls, respectively. Cold exposure increased both low (from 390 to 630 ms2 (p<0.001) and 380 to 700 ms2 (p<0.001), respectively) and high frequency heart rate variability (from 90 to 190 ms2 (p<0.001) and 150 to 300 ms2 (p<0.001), respectively), while low-to-high frequency-ratio was reduced. In addition, the frequency of ventricular ectopic beats increased slightly during cold exposure. The cold induced changes were similar between untreated hypertensive men and controls. Conclusions Short-term cold exposure with moderate facial and mild whole body cooling resulted in prolongation of T-peak to T-end interval and higher T-wave amplitude while QTc interval was shortened. These changes of ventricular repolarization may have resulted from altered cardiac autonomic regulation and were unaffected by untreated hypertension. Trial Registration ClinicalTrials.gov NCT02007031

Postexercise recovery of the spatial QRS/T angle as a predictor of sudden cardiac death

BACKGROUND Postexercise measurement of heart rate (HR) recovery and QT interval dynamics provides prognostic information in various patient populations. OBJECTIVE The purpose of this study was to assess whether the measurement of the spatial relationship between the depolarization and repolarization wavefronts (total cosine R-to-T [TCRT]) during the postexercise recovery phase would yield prognostic information. METHODS The population consisted of 1297 patients (56 ± 13 years; 67% men) who performed a clinically indicated bicycle stress test. The exercise-recovery hysteresis of TCRT was quantified from the 12-lead exercise electrocardiogram by measuring the TCRT/HR loop area bounded by the exercise and first 3-minute postexercise recovery curves. The HR-corrected TCRT/HR hysteresis was calculated by dividing the area with the HR decrement during the first 3 minutes of recovery. HR recovery was measured at 1 minute postexercise recovery. End points were cardiac death and sudden cardiac death. RESULTS During an average follow-up of 45 ± 12 months, 74 patients died (5.7%); 35 (2.6%) were cardiac deaths and 24 (1.9%) were sudden cardiac deaths. Reduced TCRT/HR loop area and TCRT/HR hysteresis were associated with cardiac mortality (P <.001). After adjustments for clinical variables, including ejection fraction, TCRT/HR loop area remained an independent predictor of cardiac death (hazard ratio 5.6; 95% confidence interval 1.6-19.1; P = .007) and sudden cardiac death (10.7; 95% confidence interval 1.4-83.7; P = .024). HR recovery did not remain a significant predictor in the multivariate analysis. CONCLUSIONS Attenuated hysteresis of the depolarization and repolarization wavefronts during postexercise recovery is associated with an increased risk of cardiac and sudden cardiac death. Analysis of repolarization dynamics from exercise electrocardiogram represents a promising tool for risk stratification.

Usefulness of Highly Sensitive Troponin as a Predictor of Short-Term Outcome in Patients With Diabetes Mellitus and Stable Coronary Artery Disease (from the ARTEMIS Study).

The aim of this study was to test the hypothesis that novel biomarkers may predict cardiac events in diabetic patients with stable coronary artery disease (CAD). Serum levels of highly sensitive troponin T (hs-TnT), B-type natriuretic peptide, highly sensitive C-reactive protein (hs-CRP), galectin-3, and soluble suppressor of tumorigenicity-2 (sST2) were analyzed in 1,137 patients with CAD and with type 2 diabetes, impaired glucose tolerance, or fasting glycaemia (diabetic group) and in 649 patients with normal glucose state. Cardiac death or hospitalization for congestive heart failure was the major end point during the follow-up of 2 years. Forty patients in the diabetic group (3.5%) and 9 patients in the nondiabetic group (1.4%) reached the primary end point. High hs-TnT level (≥14 ng/l) was the strongest predictor of the primary end point with hazard ratio of 24.5 (95% confidence interval 8.7 to 69.0; p <0.001) and remained so when adjusted for clinical variables, ejection fraction, renal, lipid, and glycemic status and other biomarkers (hazard ratio 9.9, 95% confidence interval 3.2 to 30.8; p <0.001). In the multivariate model, hs-CRP, B-type natriuretic peptide, and sST2 also predicted the primary end point in the diabetic group (p <0.01 for all). Only sST2 (p <0.001) and hs-CRP (p = 0.02) predicted the primary end point in nondiabetic group. The inclusion of hs-TnT in the model significantly improved discrimination (integrated discrimination improvement 0.050) and reclassification of the patients (net reclassification index 0.21). In conclusion, hs-TnT is a strong predictor of cardiac death or hospitalization for heart failure independently from traditional risk markers or other biomarkers in diabetic patients with stable CAD.