Interatrial block and P terminal force in the general population - Longitudinal changes, risk factors and prognosis.

BACKGROUND: Partial and advanced interatrial block (IAB) and P terminal force (PTF) in lead V1 are markers of atrial remodeling and risk factors for atrial fibrillation (AF). There is a lack of information about constancy and possible factors influencing the development of these P-wave abnormalities. METHODS: The study sample consisted of 6058 Finnish participants (mean age 52.16 ± 14.60 years, 45.0% male) from the general population with an ECG taken in a health examination, and from 3224 of these participants, who had a re-examination 11 years later. Risk factors for incident partial and advanced IAB and PTF were studied using binomial logistic regression analysis, and the prognostic significance of these ECG changes for new AF was studied using time-varying Cox regression analysis. RESULTS: The rate of reversal to normal of the studied ECG parameters were 47.4% for partial IAB, 40.0% for advanced IAB and 79.3% for PTF. Age, male sex, hypertension, higher BMI, higher LDL cholesterol, ECG left ventricular hypertrophy, use of beta blocker, and use of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist were independently associated with a risk to develop incident P-wave abnormality. Partial IAB was independently associated with increased AF risk (HR 1.28 [95% CI 1.04-1.58]), as was also advanced IAB (HR 1.72 [95% CI 1.07-2.75]). CONCLUSION: Traditional cardiovascular risk factors increase the risk of a new P-wave abnormality. Partial and advanced IAB are associated with increased AF risk. Surprisingly, P-wave abnormalities are often reversible during long-term follow-up in the general population.

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.

The prognostic significance of T-wave inversion according to ECG lead group during long-term follow-up in the general population.

BACKGROUND: Inverted T waves in the electrocardiogram (ECG) have been associated with coronary heart disease (CHD) and mortality. The pathophysiology and prognostic significance of T-wave inversion may differ between different anatomical lead groups, but scientific data related to this issue is scarce. METHODS: A representative sample of Finnish subjects (n = 6,354) aged over 30 years underwent a health examination including a 12-lead ECG in the Health 2000 survey. ECGs with T-wave inversions were divided into three anatomical lead groups (anterior, lateral, and inferior) and were compared to ECGs with no pathological T-wave inversions in multivariable-adjusted Fine-Gray and Cox regression hazard models using CHD and mortality as endpoints. RESULTS: The follow-up for both CHD and mortality lasted approximately fifteen years (median value with interquartile ranges between 14.9 and 15.3). In multivariate-adjusted models, anterior and lateral (but not inferior) T-wave inversions associated with increased risk of CHD (HR: 2.37 [95% confidence interval 1.20-4.68] and 1.65 [1.27-2.15], respectively). In multivariable analyses, only lateral T-wave inversions associated with increased risk of mortality in the entire study population (HR 1.51 [1.26-1.81]) as well as among individuals with no CHD at baseline (HR 1.59 [1.29-1.96]). CONCLUSIONS: The prognostic information of inverted T waves differs between anatomical lead groups. T-wave inversion in the anterior and lateral lead groups is independently associated with the risk of CHD, and lateral T-wave inversion is also associated with increased risk of mortality. Inverted T wave in the inferior lead group proved to be a benign phenomenon.

The prevalence and prognostic significance of interatrial block in the general population.

Introduction: Partial and advanced interatrial block (IAB) in the electrocardiographic (ECG) represents inter-atrial conduction delay. IAB is associated with atrial fibrillation (AF) and stroke in the general population.Material and methods: A representative sample of Finnish subjects (n = 6354) aged over 30 years (mean: 52.2 years, standard deviation: 14.6) underwent a health examination including a 12-lead ECG. Five different IAB groups based on automatic measurements were compared to normal P waves using multivariate-adjusted Cox proportional hazard model. Follow-up lasted up to 15 years.Results: The prevalence of advanced and partial IAB was 1.0% and 9.7%, respectively. In the multivariate model, both advanced (hazard ratio (HR): 1.63 (95% confidence interval (CI): 1.00-2.65)) and partial IAB (HR: 1.39 (1.09-1.77)) were associated with increased risk of AF. Advanced IAB was associated with increased risk of stroke or transient ischaemic attack (TIA) independently of associated AF (HR: 2.22 (1.20-4.13)). Partial IAB was also associated with increased risk of being diagnosed with coronary heart disease (HR: 1.26 (1.01-1.58)).Discussion: IAB is a rather frequent finding in the general population. IAB is a risk factor for AF and is associated with an increased risk of stroke or TIA independently of associated AF.Key messagesBoth partial and advanced interatrial block are associated with increased risk of atrial fibrillation in the general population.Advanced interatrial block is an independent risk factor for stroke and transient ischaemic attack.The clinical significance of interatrial block is dependent on the subtype classification.

Long-term prognostic significance of the ST level and ST slope in the 12­lead ECG in the general population.

BACKGROUND: Even minor ST depression in the electrocardiogram (ECG) is associated with cardiovascular disease and increased mortality. There is limited data on the prognostic significance of ST-level changes in the general population. SUBJECTS AND METHODS: A random sample of Finnish subjects (n = 6354) aged over 30 years (56.1% women) underwent a health examination including a 12­lead ECG in the Health 2000 survey. The effects of relative ST level as a continuous variable and ST slope (upsloping, horizontal, downsloping) in three different lead groups were analyzed using a multi-adjusted Cox proportional hazard model separately for men and women with total mortality as endpoint. RESULTS: The follow-up lasted for 13.7 (SD 3.3) years for men and 13.9 (SD 3.1) years for women. Lower lateral ST levels were associated with all-cause mortality in multi-adjusted models in both genders (at J + 80 ms hazard ratio [HR] 0.64 for a change of 1.0 mm [95% confidence interval 0.49-0.84, p = 0.002] for men and HR 0.61 [0.48-0.78, p < 0.001] for women). Associated coronary heart disease had no major influence on the results. Exclusion of subjects with ECG signs of left ventricular hypertrophy from the analyses increased the mortality risk of lower lateral ST levels in men but decreased it in women. For the anterior and inferior lead groups, no statistically significant difference was seen after multivariate adjustment. ST slope was not an independent predictor of mortality after multivariate adjustment. CONCLUSION: Lower ST level in the lateral ECG leads is an independent prognostic factor to predict all-cause mortality in the general population.

Heterozygous junctophilin-2 (JPH2) p.(Thr161Lys) is a monogenic cause for HCM with heart failure.

During the last two decades, mutations in sarcomere genes have found to comprise the most common cause for hypertrophic cardiomyopathy (HCM), but still significant number of patients with dominant HCM in the family are left without molecular genetic diagnosis. Next generation sequencing (NGS) does not only enable evaluation of established HCM genes but also candidate genes for cardiomyopathy are frequently tested which may lead to a situation where conclusive interpretation of the variant requires extensive family studies. We aimed to characterize the phenotype related to a variant in the junctophilin-2 (JPH2) gene, which is less known non-sarcomeric candidate gene. In addition, we did extensive review of the literature and databases about JPH2 variation in association with cardiac disease. We characterize nine Finnish index patients with HCM and heterozygous for JPH2 c.482C>A, p.(Thr161Lys) variant were included and segregation studies were performed. We identified 20 individuals affected with HCM with or without systolic heart failure and conduction abnormalities in the nine Finnish families with JPH2 p.(Thr161Lys) variant. We found 26 heterozygotes with the variant and penetrance was 71% by age 60 and 100% by age 80. Co-segregation of the variant with HCM phenotype was observed in six families. Main clinical features were left ventricular hypertrophy, arrhythmia vulnerability and conduction abnormalities including third degree AV-block. In some patients end-stage severe left ventricular heart failure with normal or mildly enlarged diastolic dimensions was detected. In conclusion, we propose that the heterozygous JPH2 p.(Thr161Lys) variant is a new Finnish mutation causing atypical HCM.

Prevalence and prognosis of ECG abnormalities in normotensive and hypertensive individuals.

OBJECTIVE: To define the prevalence and prognosis of ECG abnormalities in hypertensive individuals. METHODS: ECG, blood pressure and other cardiovascular risk factors were recorded in a nationwide population sample of 5800 Finns. The presence of 15 ECG abnormalities was evaluated. Participants were divided into categories by blood pressure and followed for coronary heart (CHD) and cardiovascular disease (CVD) events. RESULTS: Mean follow-up was 10.4 ±â€Š2.2 years. The age- and sex-adjusted prevalence rates of ECG abnormalities were generally higher in the hypertensive participants than in normotensive individuals. In multivariable-adjusted Cox models, the following ECG abnormalities predicted CHD in hypertensive participants: left ventricular hypertrophy (LVH) by Sokolow-Lyon criteria [hazard ratio, 1.47; 95% confidence interval (CI), 1.07-2.01; P = 0.02], LVH with ST-depression and negative T wave (ST/T changes) (hazard ratio, 2.31; 95% CI, 1.20-4.43, P = 0.01), ST/T changes (hazard ratio, 2.12; 95% CI, 1.34-3.36; P = 0.001), positive T wave in lead aVR (AVRT+) (hazard ratio, 1.74; 95% CI, 1.15-2.64; P = 0.009) and poor R-wave progression (hazard ratio, 2.02; 95% CI, 1.27-3.22; P = 0.003). These ECG abnormalities were also significant predictors of CVD in hypertensive participants (P ≤ 0.03 for all). Nonspecific intraventricular conduction delay predicted CVD in the whole population (hazard ratio, 1.50; 95% CI, 1.06-2.13; P = 0.02). Prolonged QT interval, abnormal P-wave indices, left axis deviation and early repolarization pattern were not associated with CHD or CVD. CONCLUSION: ECG abnormalities are highly prevalent in hypertensive individuals. LVH is still the cornerstone of cardiovascular risk assessment in hypertensive patients. The additional assessment of ST/T changes, AVRT+ and poor R-wave progression in ECGs could improve risk prediction in hypertensive patients.

Prognostic implications of intraventricular conduction delays in a general population: the Health 2000 Survey.

AIMS: We examined the prognostic impact of eight different intraventricular conduction delays (IVCD) in the standard electrocardiogram (ECG) in a community cohort. METHODS AND RESULTS: Data were collected from 6299 Finnish individuals. During a mean 8.2 years (interquartile range 8.1 to 8.3) of follow-up 640 subjects died (10.2%); 277 (4.4%) were cardiovascular deaths. For both sexes, all-cause and cardiovascular mortality was higher in subjects with IVCD than in those without. In Cox regression analysis after adjustment for age and gender, the hazard ratio for cardiovascular mortality for non-specific IVCD was 4.25 (95% confidence interval [CI] 1.95-9.26, P < 0.0001) and for left bundle branch block (LBBB) 2.11 (95% CI 1.31-3.41, P = 0.002). Right bundle branch block (RBBB) was not related to additional mortality, while incomplete RBBB (IRBBB) presented a hazard ratio of 2.24 (95% CI 1.064-4.77, P = 0.036). CONCLUSIONS: In the general population, non-specific IVCD, LBBB, and IRBBB were associated with increased relative risk for all-cause and cardiovascular mortality. RBBB did not have an impact on cardiovascular mortality either in subjects with or without previous heart disease.

Relation of positive T wave in lead aVR to risk of cardiovascular mortality.

We examined the prevalence and prognostic impact of a positive T wave in lead aVR (aVRT+) on a standard electrocardiogram in the general population. Data were collected from a large nationally representative (random sample) health examination survey conducted in Finland from 2000 through 2001. The survey consisted of 6,354 subjects (2,876 men and 3,478 women) ≥30 years who participated in the field health examination including standard electrocardiographic (ECG) recording at rest. The prevalence of aVRT+ (defined as positive or isoelectric T wave in lead aVR) was 2.2%. During the median follow-up of 98.5 months (interquartile range 96.6 to 99.6), there were 214 (3.5%) cardiovascular (CV) deaths. In Cox regression analysis after adjustment for age and gender, relative risks for CV and total mortalities associated with aVRT+ were 3.24 (95% confidence interval [CI] 2.32 to 4.54, p <0.001) and 1.91 (95% CI 1.47 to 2.49, p <0.001), respectively. In the fully adjusted model controlling for other risk factors, CV morbidity, and ECG findings, the relative risk for CV mortality for aVRT+ was 2.94 (95% CI 2.07 to 4.18, p <0.001). In conclusion, aVRT+, an easily recognized ECG finding, predicts risk for CV mortality in the general population. This finding could aid in screening for risk of total and CV mortalities.

Prognostic implications of quantitative ST-segment characteristics and T-wave amplitude for cardiovascular mortality in a general population from the Health 2000 Survey.

AIMS: We determined the gender-specific prognostic importance of quantitative measures of the ST segment and T wave in a community cohort. METHODS: Data were collected from 5613 Finnish individuals. Four electrocardiogram (ECG) lead groups were used: anterior, lateral, inferior, and lead V5. ST-segment depression, determined at four points along the ST segment, and T-wave amplitude were treated as continuous variables in Cox regression analyses. RESULTS: During a median follow-up period of 72.4 months, 120 cardiovascular deaths were registered. Among women, lateral lead group as well as lead V5 showed highly significant adjusted hazard ratios at all four ST-depression assessment points. This significance was lost in women ≥ 55 years when those with ECG-based criteria of left ventricular hypertrophy (LVH) were excluded. Results for ST-segment depression were not significant among men. As those with LVH were excluded, men ≥ 55 years showed borderline significance. T-wave amplitude did not reach significance among men, while lateral leads and lead V5 bore prognostic information among women. CONCLUSION: Quantitative ST-segment depression, regardless of the measurement point, allows prediction of cardiovascular death in women within a general population. However, the effect disappears as those with LVH are excluded. This observation highlights the need for consideration of LVH when depressed ST segments are clinically observed.

Prevalence and prognostic value of poor R-wave progression in standard resting electrocardiogram in a general adult population. The Health 2000 Survey.

AIMS: We examined the prevalence and prognostic impact of poor R-wave progression (PRWP) in a standard electrocardiogram (ECG) in a general population. METHODS: Data and standard resting ECG recording were collected from a large nationally representative (random sample) health examination survey conducted in Finland in 2000-2001. The final study population consisted of 5613 individuals. RESULTS: The prevalence of PRWP (defined as RV3 < or = 3 mm and RV2 < or = RV3) was 7.0% in women and 2.7% in men (P< or = 0.001 for difference). During follow-up of 70 +/- 9 months (mean +/- SD), 317 patients died (5.6%). Both all-cause and cardiovascular mortality was higher in the group with PRWP than in those without PRWP in both women and men. In Cox regression analysis after adjustment for age, hypertension, diabetes, previous myocardial infarction, and coronary heart disease, the relative risk for all-cause mortality for PRWP was 1.69 (95% CI 0.89-3.22, P=0.112) for men and 2.00 (95% CI 1.28-3.13, P=0.002) for women. For cardiovascular mortality the relative risk for individuals with PRWP was 1.85 (0.74-4.65, P=0.19) for men and 3.02 (1.54-5.93, P=0.001) for women. CONCLUSIONS: PRWP is a common ECG finding and predicts risk for total and cardiovascular mortality in women in a general population.