Risk of sudden cardiac death associated with QRS, QTc, and JTc intervals in the general population.

BACKGROUND: QRS duration and corrected QT (QTc) interval have been associated with sudden cardiac death (SCD), but no data are available on the significance of repolarization component (JTc interval) of the QTc interval as an independent risk marker in the general population. OBJECTIVE: In this study, we sought to quantify the risk of SCD associated with QRS, QTc, and JTc intervals. METHODS: This study was conducted using data from 3 population cohorts from different eras, comprising a total of 20,058 individuals. The follow-up period was limited to 10 years and age at baseline to 30-61 years. QRS duration and QT interval (Bazett's) were measured from standard 12-lead electrocardiograms at baseline. JTc interval was defined as QTc interval - QRS duration. Cox proportional hazards models that controlled for confounding clinical factors identified at baseline were used to estimate the relative risk of SCD. RESULTS: During a mean period of 9.7 years, 207 SCDs occurred (1.1 per 1000 person-years). QRS duration was associated with a significantly increased risk of SCD in each cohort (pooled hazard ratio [HR] 1.030 per 1-ms increase; 95% confidence interval [CI] 1.017-1.043). The QTc interval had borderline to significant associations with SCD and varied among cohorts (pooled HR 1.007; 95% CI 1.001-1.012). JTc interval as a continuous variable was not associated with SCD (pooled HR 1.001; 95% CI 0.996-1.007). CONCLUSION: Prolonged QRS durations and QTc intervals are associated with an increased risk of SCD. However, when the QTc interval is deconstructed into QRS and JTc intervals, the repolarization component (JTc) appears to have no independent prognostic value.

Asystole episodes and bradycardia in patients with end-stage renal disease.

BACKGROUND: Knowledge of arrhythmias in patients with end-stage renal disease (ESRD) is mainly based on ambulatory electrocardiography (ECG) studies and observations during haemodialysis (HD). We used insertable cardiac monitors (ICMs) to define the prevalence of arrhythmias, focusing on bradyarrhythmias, in ESRD patients treated with several dialysis modes including home therapies. Moreover, we assessed whether these arrhythmias were detected in baseline or ambulatory ECG recordings. METHODS: Seventy-one patients with a subcutaneous ICM were followed for up to 3 years. Asystole (≥4.0 s) and bradycardia (heart rate <30 bpm for ≥4 beats) episodes, ventricular tachyarrhythmias and atrial fibrillation (AF) were collected and verified visually. A baseline ECG and a 24- to 48-h ambulatory ECG were recorded at recruitment and once a year thereafter. RESULTS: At recruitment, 44 patients were treated in in-centre HD, 12 in home HD and 15 in peritoneal dialysis. During a median follow-up of 34.4 months, 18 (25.4%) patients had either an asystolic or a bradycardic episode. The median length of each patient's longest asystole was 6.6 s and that of a bradycardia 13.5 s. Ventricular tachyarrhythmias were detected in 16 (23%) patients, and AF in 34 (51%) patients. In-centre HD and Type II diabetes were significantly more frequent among those with bradyarrhythmias, whereas no bradyarrhythmias were found in home HD. No bradyarrhythmias were evident in baseline or ambulatory ECG recordings. CONCLUSIONS: Remarkably many patients with ESRD had bradycardia or asystolic episodes, but these arrhythmias were not detected by baseline or ambulatory ECG.

Hydroxychloroquine reduces interleukin-6 levels after myocardial infarction: The randomized, double-blind, placebo-controlled OXI pilot trial.

OBJECTIVES: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. METHOD: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. RESULTS: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to interruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups). CONCLUSIONS: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocardial infarction.

Electrocardiographic Risk Markers for Heart Failure in Women Versus Men.

Heart failure (HF) is one of the leading causes of hospitalization in the Western world. Women have a lower HF hospitalization rate and mortality compared with men. The role of electrocardiography as a risk marker of future HF in women is not well known. We studied association of electrocardiographic (ECG) risk factors for HF hospitalization in women from a large middle-aged general population with a long-term follow-up and compared the risk profile to men. Standard 12-lead ECG markers were analyzed from 10,864 subjects (49% women), and their predictive value for HF hospitalization was analyzed. During the follow-up (30 ± 11 years), a total of 1,743 subjects had HF hospitalization; of these, 861 were women (49%). Several baseline characteristics, such as age, body mass index, blood pressure, and history of previous cardiac disease predicted the occurrence of HF both in women and men (p <0.001 for all). After adjusting for baseline variables, ECG sign of left ventricular hypertrophy (LVH) (p <0.001), and atrial fibrillation (p <0.001) were the only baseline ECG variables that predicted future HF in women. In men, HF was predicted by fast heart rate (p = 0.008), T wave inversions (p <0.001), abnormal Q-waves (p = 0.002), and atrial fibrillation (p <0.001). Statistically significant gender interactions in prediction of HF were observed in ECG sign of LVH, inferolateral T wave inversions, and heart rate. In conclusion, ECG sign of LVH predicts future HF in middle-aged women, and T wave inversions and elevated heart rate are associated with HF hospitalization in men.

Fluid overload is an independent predictor of atrial fibrillation in end-stage renal disease: A prospective study using insertable cardiac and body composition monitors
.

BACKGROUND: Fluid overload and atrial fibrillation (AF) are frequently encountered in patients with end-stage renal disease (ESRD). We used subcutaneously insertable cardiac monitors (ICM) to detect AF and associated it with the hydration status, determined with a body composition monitor (BCM) in dialysis patients. MATERIALS AND METHODS: 69 patients were recruited. Fluid overload was defined based on BCM measurements as a ratio of overhydration (OH) and extracellular water (OH/ECW) of > 15% at baseline. AF episodes lasting ≥ 2 minutes were collected. RESULTS: 45 in-center hemodialysis patients, 11 on peritoneal dialysis, 12 on home hemodialysis, and 1 predialysis-stage patient were followed up for a median of 2.9 years (25th - 75th percentile 1.9 - 3.1). 29% were overhydrated at baseline, and the percentage remained similar throughout the study. Overhydrated patients had a lower body mass index, a higher prevalence of type 1 diabetes mellitus (DM) and diabetic nephropathy, higher systolic blood pressure, greater ultrafiltration (UF) during dialysis, and a smaller lean tissue index than normohydrated patients. Chronic or paroxysmal AF was known to occur in 20.3% at entry, and a further 33.3% developed AF during the study, with an overall prevalence 53.6%. In univariable logistic regression, OH/ECW > 15% was strongly associated with AF prevalence (OR 6.8, 95% CI 1.7 - 26.5, p = 0.006), as were UF, age, coronary heart disease (CHD), DM, and the echocardiogram-derived ejection fraction and left atrial diameter. In multivariable analyses, OH/ECW > 15% remained an independent predictor of AF alongside age and CHD. CONCLUSION: The occurrence of AF is independently associated with BCM-measured fluid overload, which is common among ESRD patients.

Gender differences in prevalence and prognostic value of fragmented QRS complex.

BACKGROUND: Fragmented QRS (fQRS) on 12-lead electrocardiogram (ECG) is associated with scarred myocardium and adverse outcome. However, the data on gender differences in terms of its prevalence and prognostic value is sparse. The aim of this study was to evaluate whether gender differences in fQRS exist among subjects drawn from populations with different risk profiles. METHODS: We analyzed fQRS from 12-lead ECG in 953 autopsy-confirmed victims of sudden cardiac death (SCD) (78% men; 67.0 ± 11.4 yrs), 1900 coronary artery disease (CAD) patients with angiographically confirmed stenosis of ≥50% (70% men; 66.6 ± 9.0 yrs, 43% with previous myocardial infarction [MI]), and in 10,904 adults drawn from the Finnish adult general population (52% men; 44.0 ± 8.5 yrs). RESULTS: Prevalence of fQRS was associated with older age, male sex and the history and severity of prior cardiac disease of subjects. Among the general population fQRS was more commonly found among men in comparison to women (20.5% vs. 14.8%, p < 0.001). The prevalence of fQRS rose gradually along with the severity of prior cardiac disease in both genders, yet remained significantly higher in the male population: subjects with suspected or known cardiac disease (25.4% vs. 15.8% p < 0.001), CAD patients without prior MI (39.9% vs. 26.4%, p < 0.001), CAD patients with prior MI (42.9% vs. 31.2%, p < 0.001), and victims of SCD (56.4% vs. 44.4%, p < 0.001). CONCLUSIONS: The prevalence of QRS fragmentation varies in different populations. The fragmentation is clearly related to the underlying cardiac disease in both genders, however women seem to have significantly lower prevalence of fQRS in each patient population in comparison to men.

Electrocardiographic Risk Markers of Cardiac Death: Gender Differences in the General Population.

BACKGROUND: Cardiac death is one of the leading causes of death and sudden cardiac death (SCD) is estimated to cause approximately 50% of cardiac deaths. Men have a higher cardiac mortality than women. Consequently, the mechanisms and risk markers of cardiac mortality are not as well defined in women as they are in men. AIM: The aim of the study was to assess the prognostic value and possible gender differences of SCD risk markers of standard 12-lead electrocardiogram in three large general population samples. METHODS: The standard 12-lead electrocardiographic (ECG) markers were analyzed from three different Finnish general population samples including total of 20,310 subjects (49.9% women, mean age 44.8 ± 8.7 years). The primary endpoint was cardiac death, and SCD and all-cause mortality were secondary endpoints. The interaction effect between women and men was assessed for each ECG variable. RESULTS: During the follow-up (7.7 ± 1.2 years), a total of 883 deaths occurred (24.5% women, p < 0.001). There were 296 cardiac deaths (13.9% women, p < 0.001) and 149 SCDs (14.8% women, p < 0.001). Among those who had died due to cardiac cause, women had more often a normal electrocardiogram compared to men (39.0 vs. 27.5%, p = 0.132). After adjustments with common cardiovascular risk factors and the population sample, the following ECG variables predicted the primary endpoint in men: left ventricular hypertrophy (LVH) with strain pattern (p < 0.001), QRS duration > 110 ms (p < 0.001), inferior or lateral T-wave inversion (p < 0.001) and inferolateral early repolarization (p = 0.033). In women none of the variables remained significant predictors of cardiac death in multivariable analysis, but LVH, QTc ≥ 490 ms and T-wave inversions predicted SCD (p < 0.047 and 0.033, respectively). In the interaction analysis, LVH (HR: 2.4; 95% CI: 1.2-4.9; p = 0.014) was stronger predictor of primary endpoint in women than in men. CONCLUSION: Several standard ECG variables provide independent information on the risk of cardiac mortality in men but not in women. LVH and T-wave inversions predict SCD also in women.

Predicting sudden cardiac death in a general population using an electrocardiographic risk score.

OBJECTIVE: We investigated whether combining several ECG abnormalities would identify general population subjects with a high sudden cardiac death (SCD) risk. METHODS: In a sample of 6830 participants (mean age 51.2±13.9 years; 45.5% male) in the Mini-Finland Health Survey, a general population cohort representative of the Finnish adults aged ≥30 years conducted in 1978-1980, we examined their ECGs, following subjects for 24.3±10.4 years. We analysed the association between individual ECG abnormalities and 10-year SCD risk and developed a risk score using five ECG abnormalities independently associated with SCD risk: heart rate >80 beats per minute, PR duration >220 ms, QRS duration >110 ms, left ventricular hypertrophy and T-wave inversion. We validated the score using an external general population cohort of 10 617 subjects (mean age 44.0±8.5 years; 52.7% male). RESULTS: No ECG abnormalities were present in 4563 subjects (66.8%), while 96 subjects (1.4%) had ≥3 ECG abnormalities. After adjusting for clinical factors, the SCD risk increased progressively with each additional ECG abnormality. Subjects with ≥3 ECG abnormalities had an HR of 10.23 (95% CI 5.29 to 19.80) for SCD compared with those without abnormalities. The risk score similarly predicted SCD risk in the validation cohort, in which subjects with ≥3 ECG abnormalities had HR 10.82 (95% CI 3.23 to 36.25) for SCD compared with those without abnormalities. CONCLUSION: The ECG risk score successfully identified general population subjects with a high SCD risk. Combining ECG risk markers may improve the risk stratification for SCD.

Long-term prognostic impact of hyperuricemia in community.

The debate whether an elevated level of serum uric acid (SUA) is an independent marker of cardiovascular risk is still going on. We examined morbidity and mortality related to SUA and hyperuricemia in a well-characterized population with very long follow-up. Study included 4696 participants (aged 30-59 years at baseline) of the coronary heart disease (CHD) Study of the Finnish Mobile Clinic Health Examination Survey. Adjusted hazard ratios (HRs) of hyperuricemia (defined as ≥360 µmol/l and ≥420 µmol/l) and SUA quintiles for mortality and adverse cardiovascular outcomes are reported. During the mean follow up of 30.6 years there were 2723 deaths, 887 deaths for CHD of which 340 were classified as sudden cardiac deaths, 1642 hospitalizations due to CHD and 798 hospitalizations due to congestive heart failure. After adjusting to baseline risk factors and presence of cardiovascular diseases as well as the use of diuretics there were no significant differences in the risk of any of the outcomes when analyzed either according to quintiles of SUA or using a cut-off point SUA ≥360 µmol/l for hyperuricemia. Only a rare finding of hyperuricemia SUA ≥420 µmol/l among women (n = 17, 0.9%) was independently associated with significantly higher risk of mortality (adjusted HR: 2.59, 95% CI: 1.54-4.34) and a combination end-point of major adverse cardiac events (MACEs) (HR: 2.69; 95% CI: 1.56-4.66). SUA was not an independent indicator of morbidity and mortality, with the exception of particularly high levels of SUA among women.

Electrocardiogram as a predictor of sudden cardiac death in middle-aged subjects without a known cardiac disease.

BACKGROUND: Abnormal 12­lead electrocardiogram (ECG) findings and proposing its ability for enhanced risk prediction, majority of the studies have been carried out with elderly populations with prior cardiovascular diseases. This study aims to denote the association of sudden cardiac death (SCD) and various abnormal ECG morphologies using middle-aged population without a known cardiac disease. METHODS: In total, 9511 middle-aged subjects (mean age 42 ±â€¯8.2 years, 52% males) without a known cardiac disease were included in this study. Risk for SCD was assessed after 10 and 30-years of follow-up. RESULTS: Abnormal ECG was present in 16.3% (N = 1548) of subjects. The incidence of SCD was distinctly higher among those with any ECG abnormality in 10 and 30-year follow-ups (1.7/1000 years vs. 0.6/1000 years, P < 0.001; 3.4/1000 years vs. 1.9/1000 years, P < 0.001). At 10-year point, competing risk multivariate regression model showed HR of 1.62 (95% CI 1.0-2.6, P = 0.05) for SCD in subjects with abnormal ECG. QRS duration ≥ 110 ms, QRST-angle > 100°, left ventricular hypertrophy, and T-wave inversions were the most significant independent ECG risk markers for 10-year SCD prediction with up to 3-fold risk for SCD. Those with ECG abnormalities had a 1.3-fold risk (95% CI 1.07-1.57, P = 0.007) for SCD in 30-year follow-up, whereas QRST-angle > 100°, LVH, ER ≥ 0.1 mV and ≥0.2 mV were the strongest individual predictors. Subjects with multiple ECG abnormalities had up to 6.6-fold risk for SCD (P < 0.001). CONCLUSION: Several ECG abnormalities are associated with the occurrence of early and late SCD events in the middle-age subjects without known history of cardiac disease.

Fragmented QRS complex as a predictor of exercise-related sudden cardiac death.

INTRODUCTION: Little is known about the association between electrocardiographic abnormalities and exercise-related sudden cardiac death. Therefore, our aim was to identify possible electrocardiographic findings related to exercise-induced sudden cardiac death. METHODS AND RESULTS: The FinGesture study includes 3,989 consecutive sudden cardiac deaths in northern Finland between 1998 and 2012, out of whom a total of 647 subjects had a previously recorded electrocardiography acquired from the archives of Oulu University Hospital. In 276 of these cases the death was witnessed, and the activity at the time of death was either rest or physical exercise (PE); in 40 (14%) cases sudden cardiac death was exercise-related and in 236 (86%) cases death took place at rest. Fragmented QRS complex in at least two consecutive leads within anterior leads (V1-V3) was more common in the exercise-group compared to rest-group (17 of 40, 43% vs. 51 of 236, 22%, P  =  0.005). Pathologic Q wave in anterior leads was more common in the PE group (9 of 40, 23% vs. 26 of 236, 11%; P  =  0.044). Median QRS duration was prolonged in the exercise-group compared to the rest-group (100 milliseconds vs. 94 milliseconds, P = 0.047). QTc interval, the prevalence of inverted T-waves, or other electrocardiographic abnormalities did not differ significantly between the two groups. CONCLUSIONS: As a conclusion, fragmented QRS complex in the anterior leads is associated with an increased risk of sudden cardiac death during PE.

Case reports of two pedigrees with recessive arrhythmogenic right ventricular cardiomyopathy associated with homozygous Thr335Ala variant in DSG2.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease, involving changes in ventricular myocardial tissue and leading to fatal arrhythmias. Mutations in desmosomal genes are thought to be the main cause of ARVC. However, the exact molecular genetic etiology of the disease still remains largely inconclusive, and this along with large variabilities in clinical manifestations complicate clinical diagnostics. CASE PRESENTATION: We report two families (n = 20) in which a desmoglein-2 (DSG2) missense variant c.1003A > G, p.(Thr335Ala) was discovered in the index patients using next-generation sequencing panels. The presence of this variant in probands' siblings and children was studied by Sanger sequencing. Five homozygotes and nine heterozygotes were found with the mutation. Participants were evaluated clinically where possible, and available medical records were obtained. All patients homozygous for the variant fulfilled the current diagnostic criteria for ARVC, whereas none of the heterozygous subjects had symptoms suggestive of ARVC or other cardiomyopathies. CONCLUSIONS: The homozygous DSG2 variant c.1003A > G co-segregated with ARVC, indicating autosomal recessive inheritance and complete penetrance. More research is needed to establish a detailed understanding of the relevance of rare variants in ARVC associated genes, which is essential for informative genetic counseling and rational family member testing.

The ability of an electrocardiogram to predict fatal and non-fatal cardiac events in asymptomatic middle-aged subjects.

INTRODUCTION: The long-term prognostic value of a standard 12-lead electrocardiogram (ECG) for predicting cardiac events in apparently healthy middle-aged subjects is not well defined. MATERIALS AND METHODS: A total of 9511 middle-aged subjects (mean age 43 ± 8.2 years, 52% males) without a known cardiac disease and with a follow-up 40 years were included in the study. Fatal and non-fatal cardiac events were collected from the national registries. The predictive value of ECG was separately analyzed for 10 and 30 years. Major ECG abnormalities were classified according to the Minnesota code. RESULTS: Subjects with major ECG abnormalities (N = 1131) had an increased risk of cardiac death after 10-years (adjusted hazard ratio [HR] 1.7; 95% confidence interval [95% CI], 1.1-2.5, p = 0.009) and 30-years of follow-up (HR 1.3, 95% CI, 1.1-1.5, p < 0.001). Model discrimination measured with the C-index showed only a minor improvement with the inclusion of ECG abnormalities: 0.851 versus 0.853 and 0.742 versus 0.743 for 10- and 30-year follow-up, respectively. ECG did not predict non-fatal cardiac events after 10-years or 30-years of follow-up. DISCUSSION: Major ECG abnormalities are associated with an increased risk of short and long-term cardiac mortality in middle-aged subjects. However, the improvement in discrimination between subjects with and without fatal cardiac events was marginal with abnormal ECG. KEY MESSAGES: Abnormalities observed on 12-lead electrocardiogram are shown to have prognostic significance for cardiac events in elderly subjects without known cardiac disease. Our results suggest that ECG abnormalities increase the risk of fatal cardiac events also in middle-aged healthy subjects.

[Myocardial infarction in a patient free of coronary artery disease]. / Tervesydämisen migreenipotilaan sydäninfarkti.

Triptans are widely used for treating migraine attacks. Their mechanism of action is attributable to cerebrovascular vasoconstriction. Vasoconstriction can occur also in the coronary arteries. Mild chest symptoms not related to myocardial ischemia have been reported among triptan users. Severe cardiovascular events have also been reported, but they are extremely rare. There are few observational studies focusing on the cardiovascular risks of triptans. Triptans are nevertheless considered contra-indicated in patients with coronary artery disease. We report a case of zolmitriptan-induced myocardial infarction in a patient free of coronary artery disease.

Diabetes, glucose tolerance, and the risk of sudden cardiac death.

BACKGROUND: Diabetes predisposes to sudden cardiac death (SCD). However, it is uncertain whether greater proportion of cardiac deaths are sudden among diabetes patients than other subjects. It is also unclear whether the risk of SCD is pronounced already early in the course of the disease. The relationship of impaired glucose tolerance (IGT) and SCD is scarcely documented. METHODS: A general population cohort of 10594 middle-aged subjects (mean age 44 years, 52.6 % male, follow-up duration 35-41 years) was divided into diabetes patients (n = 82), subjects with IGT (n = 3806, plasma glucose ≥9.58 mmol/l in one-hour glucose tolerance test), and controls (n = 6706). RESULTS: Diabetes patients had an increased risk of SCD after adjustment confounders (hazard ratio 2.62, 95 % confidence interval 1.46-4.70, p = 0.001) but risk for non-sudden cardiac death was similarly increased and the proportion of SCD of cardiac deaths was not increased. The SCD risk persisted after exclusion of subjects with baseline cardiac disease or non-fatal cardiac events during the follow-up. Subjects with IGT were at increased risk for SCD (univariate hazard ratio 1.51; 95 % confidence interval 1.31-1.74; p < 0.001) and also for non-sudden cardiac deaths and non-fatal cardiac events but adjustments for other risk factors attenuated these effects. CONCLUSIONS: Diabetes was associated with increased risk of SCD but also the risk of non-sudden cardiac death was similarly increased. The proportion of cardiac deaths being sudden in subjects with diabetes was not increased. The higher SCD risk in diabetes patients was independent of known cardiac disease at baseline or occurrence of non-fatal cardiac event during the follow-up.

Body Mass Index as a Predictor of Sudden Cardiac Death and Usefulness of the Electrocardiogram for Risk Stratification.

Evidence of the role of body mass index (BMI) as a risk factor for sudden cardiac death (SCD) is conflicting, and how electrocardiographic (ECG) SCD risk markers perform in subjects with different BMIs is not known. In this study, a general population cohort consisting of 10,543 middle-aged subjects (mean age 44 years, 52.7% men) was divided into groups of lean (BMI <20, n = 374), normal weight (BMI 20.0 to 24.9, n = 4,334), overweight (BMI 25.0 to 29.9, n = 4,390), and obese (BMI >30, n = 1,445) subjects. Cox proportional hazards models adjusted for confounders were used to assess the risk for SCD associated with BMI and the risk for SCD associated with ECG abnormalities in subjects with different BMIs. The overweight and obese subjects were at increased risk for SCD (hazard ratios [95% CIs] were 1.33 [1.13 to 1.56], p = 0.001 and 1.79 [1.44 to 2.23], p <0.001 for overweight and obese subjects, respectively). The risk of non-SCD had a similar relation with BMI as SCD. Hazard ratios associated with ECG abnormalities were 3.03, 1.75, 1.74, and 1.34 in groups of lean, normal weight, overweight, and obese subjects, respectively, but no statistical significance was reached in the obese. ECG abnormalities improved integrated discrimination indexes and continuous net reclassification indexes statistically significantly only in the normal weight group. In conclusion, the overweight and obese are at increased risk for SCD but also for non-SCD, and ECG abnormalities are associated with increased risk of SCD also in normal weight subjects presenting with less traditional cardiovascular risk factors.

Usefulness of exercise test in the diagnosis of short QT syndrome.

AIMS: Short QT syndrome (SQTS) is a rare arrhythmogenic inherited heart disease. Diagnosis can be challenging in subjects with slightly shortened QT interval at electrocardiogram. In this study we compared the QT interval behaviour during exercise in a cohort of SQTS patients with a control group, to evaluate the usefulness of exercise test in the diagnosis of SQTS. METHODS AND RESULTS: Twenty-one SQTS patients and 20 matched control subjects underwent an exercise test. QT interval was measured at different heart rates (HRs), at rest and during effort. The relation between QT interval and HR was evaluated by linear regression analysis according to the formula: QT = ß ×HR + α, where ß is the slope of the linear relation, and α is the intercept. Rest and peak exercise HRs were not different in the two groups. Short QT syndrome patients showed lower QT intervals as compared with controls both at rest (276 ± 27 ms vs. 364 ± 25 ms, P < 0.0001) and at peak exercise (228 ± 27 ms vs. 245 ± 26 ms, P = 0.05), with a mean variation from rest to peak effort of 48 ± 14 ms vs. 120 ± 20 ms (P < 0.0001). Regression analysis of QT/HR relationship revealed a less steep slope for SQTS patients compared with the control group, never exceeding the value of -0.90 ms/beat/min (mean value -0.53 ± 0.15 ms/beat/min vs. -1.29 ± 0.30 ms/beat/min, P < 0.0001). CONCLUSION: Short QT syndrome patients show a reduced adaptation of the QT interval to HR. Exercise test can be a useful tool in the diagnosis of SQTS.

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.

Delayed QRS transition in the precordial leads of an electrocardiogram as a predictor of sudden cardiac death in the general population.

BACKGROUND: QRS transition zone is related to the electrical axis of the heart in the horizontal plane and is easily determined from the precordial leads of a standard 12-lead ECG. However, whether delayed QRS transition, or clockwise rotation of the heart, carries prognostic implications and predicts sudden cardiac death (SCD) is unclear. OBJECTIVE: The purpose of this study was to study whether delayed transition is associated with mortality and SCD. METHODS: We evaluated 12-lead ECGs of 10,815 Finnish middle-aged subjects from the general population (52% men, mean age 44 ± 8.5 years) and followed them for 30 ± 11 years. Main end-points were mortality and SCD. RESULTS: Delayed QRS transition at lead V4 or later occurred in 1770 subjects (16.4%) and markedly delayed transition at lead V5 or later in 146 subjects (1.3%). Delayed transition zone was associated with older age, male gender, higher body mass index, hypertension, baseline cardiovascular disease, leftward shift of the frontal QRS axis, wider QRS-T angle, and ECG left ventricular hypertrophy. After adjusting for several clinical and ECG variables, delayed transition was associated with overall mortality (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.07-1.22, P < .001) and SCD (HR 1.23, 95% CI 1.03-1.47, P = .029). Markedly delayed transition at V5 or later predicted significantly SCD (HR 1.89, 95% CI 1.18-3.03, P = .008) and all-cause mortality (HR 1.30, 95% CI 1.07-1.58, P = .01). However, further adjustments for repolarization abnormalities attenuated this effect. CONCLUSION: Delayed QRS transition in the precordial leads of an ECG seems to be a novel ECG risk marker for SCD. In particular, markedly delayed transition was associated with significantly increased risk of SCD, independent of confounding factors.