Development of autonomic heart rate modulations during childhood and adolescence.

Autonomic control of heart rate is well known in adult subjects, but limited data are available on the development of the heart rate control during childhood and adolescence. Continuous 12-lead electrocardiograms were recorded in 1045 healthy children and adolescents (550 females) aged 4 to 19 years during postural manoeuvres involving repeated 10-min supine, unsupported sitting, and unsupported standing positions. In each position, heart rate was measured, and heart rate variability indices were evaluated (SDNN, RMSSD, and high (HF) and low (LF) frequency components were obtained). Quasi-normalized HF frequency components were defined as qnHF = HF/(HF + LF). These measurements were, among others, related to age using linear regressions. In supine position, heart rate decreases per year of age were significant in both sexes but lower in females than in males. In standing position, these decreases per year of age were substantially lowered. RMSSD and qnHF indices were independent of age in supine position but significantly decreased with age in sitting and standing positions. Correspondingly, LF/HF proportions showed steep increases with age in sitting and standing positions but not in the supine position. The study suggests that baseline supine parasympathetic influence shows little developmental changes during childhood and adolescence but that in young children, sympathetic branch is less responsive to vagal influence. While vagal influences modulate cardiac periods in young and older children equally, they are less able to suppress the sympathetic influence in younger children.

QRS micro-fragmentation as a mortality predictor.

AIMS: Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology. METHODS AND RESULTS: A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS 'micro'-fragmentation, QRS-µf) between the original and reconstructed signals. QRS 'micro'-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS-µf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS 'macro'-fragmentation, QRS-Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS-µf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS-µf prospectively at 3.5%. When QRS-µf was used in multivariable analyses, QRS-Mf and QRS duration lost their predictive value. CONCLUSION: In three populations with different clinical characteristics, QRS-µf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS-µf values are likely responsible for the predictive power of visible QRS-Mf.

The role of computed tomography pulmonary angiography in COVID-19 patients with suspected pulmonary embolism.

OBJECTIVES: This study is aimed to determine the location and distribution of pulmonary embolism (PE) and presence of signs potentially indicative of right heart overload on computed tomography pulmonary angiography (CTPA) in COVID-19 and non-COVID-19 patients. We also evaluated the extent and severity of COVID-19-associated lung changes in relation to PE. METHODS: The total number of 1,698 patients with CTPA included in the study were divided into 2 groups according to their COVID-19 status and each group was divided into 2 subgroups based on their PE status. These groups and subgroups were compared in terms of location of PE, diameter of pulmonary artery, right heart strain, ground-glass opacities (GGO), consolidations and other imaging features. RESULTS: In COVID-19 patients, there was a significant predominance of PE in peripheral branches of pulmonary artery (p < 0.001). There was an increased right-to-left ratio of ventricular diameters in cases with PE (p = 0.032 in patients with COVID-19 and p < 0.001 in non-COVID-19 patients). There was no association between the extent and severity of the disease and distribution of PE. CONCLUSION: COVID-19 is associated with a higher incidence of peripheral location of PE and presence of GGO. There were signs indicative of right heart overload in cases with PE regardless of COVID-19 (Tab. 3, Fig. 1, Ref. 29) Keywords: COVID-19, computed tomography, CTPA, pneumonia, pulmonary embolism.

Q waves are the strongest electrocardiographic variable associated with primary prophylactic implantable cardioverter-defibrillator benefit: a prospective multicentre study.

AIM: The association of standard 12-lead electrocardiogram (ECG) markers with benefits of the primary prophylactic implantable cardioverter-defibrillator (ICD) has not been determined in the contemporary era. We analysed traditional and novel ECG variables in a large prospective, controlled primary prophylactic ICD population to assess the predictive value of ECG in terms of ICD benefit. METHODS AND RESULTS: Electrocardiograms from 1477 ICD patients and 700 control patients (EU-CERT-ICD; non-randomized, controlled, prospective multicentre study; ClinicalTrials.gov Identifier: NCT02064192), who met ICD implantation criteria but did not receive the device, were analysed. The primary outcome was all-cause mortality. In ICD patients, the co-primary outcome of first appropriate shock was used. Mean follow-up time was 2.4 ± 1.1 years to death and 2.3 ± 1.2 years to the first appropriate shock. Pathological Q waves were associated with decreased mortality in ICD patients [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.35-0.84; P < 0.01] and patients with pathological Q waves had significantly more benefit from ICD (HR 0.44, 95% CI 0.21-0.93; P = 0.03). QTc interval increase taken as a continuous variable was associated with both mortality and appropriate shock incidence, but commonly used cut-off values, were not statistically significantly associated with either of the outcomes. CONCLUSION: Pathological Q waves were a strong ECG predictor of ICD benefit in primary prophylactic ICD patients. Excess mortality among Q wave patients seems to be due to arrhythmic death which can be prevented by ICD.

Polyscore of autonomic parameters for risk stratification of the elderly general population: the Polyscore study.

AIMS: Present society is constantly ageing and elderly frequently suffer from conditions that are difficult and/or costly to treat if detected late. Effective screening of the elderly is therefore needed so that those requiring detailed clinical work-up are identified early. We present a prospective validation of a screening strategy based on a Polyscore of seven predominantly autonomic, non-invasive risk markers. METHODS AND RESULTS: Within a population-based survey in Germany (INVADE study), participants aged ≥60 years were enrolled between August 2013 and February 2015. Seven prospectively defined Polyscore components were obtained during 30-min continuous recordings of electrocardiogram, blood pressure, and respiration. Out of 1956 subjects, 168 were excluded due to atrial fibrillation, implanted pacemaker, or unsuitable recordings. All-cause mortality over a median 4-year follow-up was prospectively defined as the primary endpoint. The Polyscore divided the investigated population (n = 1788, median age: 72 years, females: 58%) into three predefined groups with low (n = 1405, 78.6%), intermediate (n = 326, 18.2%), and high risk (n = 57, 3.2%). During the follow-up, 82 (4.6%) participants died. Mortality in the Polyscore-defined risk groups was 3.4%, 7.4%, and 17.5%, respectively (P < 0.0001). The Polyscore-based mortality prediction was independent of Framingham score, diabetes, chronic kidney disease, and major stroke and/or myocardial infarction history. It was particularly effective in those aged <75 years (n = 1145). CONCLUSION: The Polyscore-based mortality risk assessment from short-term non-invasive recordings is effective in the elderly general population, especially those aged 60-74 years. Implementation of a comprehensive Polyscore screening of this age group is proposed to advance preventive medical care.

Clinical effectiveness of primary prevention implantable cardioverter-defibrillators: results of the EU-CERT-ICD controlled multicentre cohort study.

AIMS: The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy. METHODS AND RESULTS: We recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537-0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class

Prediction of mortality benefit based on periodic repolarisation dynamics in patients undergoing prophylactic implantation of a defibrillator: a prospective, controlled, multicentre cohort study.

BACKGROUND: A small proportion of patients undergoing primary prophylactic implantation of implantable cardioverter defibrillators (ICDs) experiences malignant arrhythmias. We postulated that periodic repolarisation dynamics, a novel marker of sympathetic-activity-associated repolarisation instability, could be used to identify electrically vulnerable patients who would benefit from prophylactic implantation of ICDs by way of a reduction in mortality. METHODS: We did a prespecified substudy of EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD), a prospective, investigator-initiated, non-randomised, controlled cohort study done at 44 centres in 15 EU countries. Patients aged 18 years or older with ischaemic or non-ischaemic cardiomyopathy and reduced left ventricular ejection fraction (≤35%) were eligible for inclusion if they met guideline-based criteria for primary prophylactic implantation of ICDs. Periodic repolarisation dynamics from 24-h Holter recordings were assessed blindly in patients the day before ICD implantation or on the day of study enrolment in patients who were conservatively managed. The primary endpoint was all-cause mortality. Propensity scoring and multivariable models were used to assess the interaction between periodic repolarisation dynamics and the treatment effect of ICDs on mortality. FINDINGS: Between May 12, 2014, and Sept 7, 2018, 1371 patients were enrolled in our study. 968 of these patients underwent ICD implantation, and 403 were treated conservatively. During follow-up (median 2·7 years [IQR 2·0-3·3] in the ICD group and 1·2 years [0·8-2·7] in the control group), 138 (14%) patients died in the ICD group and 64 (16%) patients died in the control group. We noted a 43% reduction in mortality in the ICD group compared with the control group (adjusted hazard ratio [HR] 0·57 [95% CI 0·41-0·79]; p=0·0008). Periodic repolarisation dynamics significantly predicted the treatment effect of ICDs on mortality (adjusted p=0·0307). The mortality benefits associated with ICD implantation were greater in patients with periodic repolarisation dynamics of 7·5 deg or higher (n=199; adjusted HR 0·25 [95% CI 0·13-0·47] for the ICD group vs the control group; p<0·0001) than in those with periodic repolarisation dynamics less than 7·5 deg (n=1166; adjusted HR 0·69 [95% CI 0·47-1·00]; p=0·0492; pinteraction=0·0056). The number needed to treat was 18·3 (95% CI 10·6-4895·3) in patients with periodic repolarisation dynamics less than 7·5 deg and 3·1 (2·6-4·8) in those with periodic repolarisation dynamics of 7·5 deg or higher. INTERPRETATION: Periodic repolarisation dynamics predict mortality reductions associated with prophylactic implantation of ICDs in contemporarily treated patients with ischaemic or non-ischaemic cardiomyopathy. Periodic repolarisation dynamics could help to guide treatment decisions about prophylactic ICD implantation. FUNDING: The European Community's 7th Framework Programme.

Sources of QTc variability: Implications for effective ECG monitoring in clinical practice.

Pharmaceuticals that prolong ventricular repolarization may be proarrhythmic in susceptible patients. While this fact is well recognized, schemes for sequential QTc interval monitoring in patients receiving QT-prolonging drugs are frequently overlooked or, if implemented, underutilized in clinical practice. There are several reasons for this gap in day-to-day clinical practice. One of these is the perception that serially measured QTc intervals are subject to substantial variability that hampers the distinction between potential proarrhythmic signs and other sources of QTc variability. This review shows that substantial part of the QTc variability can be avoided if more accurate methodology for electrocardiogram collection, measurement, and interpretation is used. Four aspects of such a methodology are discussed. First, advanced methods for QT interval measurement are proposed including suggestion of multilead measurements in problematic recordings such as those in atrial fibrillation patients. Second, serial comparisons of T-wave morphologies are advocated instead of simple acceptance of historical QTc measurements. Third, the necessity of understanding the pitfalls of heart rate correction is stressed including the necessity of avoiding the Bazett correction in cases of using QTc values for clinical decisions. Finally, the frequently overlooked problem of QT-heart rate hysteresis is discussed including the possibility of gross QTc errors when correcting the QT interval for simultaneously measured short-term heart rate.

Problems with Bazett QTc correction in paediatric screening of prolonged QTc interval.

BACKGROUND: Bazett formula is frequently used in paediatric screening for the long QT syndrome (LQTS) and proposals exist that using standing rather than supine electrocardiograms (ECG) improves the sensitivity of LQTS diagnosis. Nevertheless, compared to adults, children have higher heart rates (especially during postural provocations) and Bazett correction is also known to lead to artificially prolonged QTc values at increased heart rates. This study assessed the incidence of erroneously increased QTc values in normal children without QT abnormalities. METHODS: Continuous 12-lead ECGs were recorded in 332 healthy children (166 girls) aged 10.7 ± 2.6 years while they performed postural manoeuvring consisting of episodes (in the following order) of supine, sitting, standing, supine, standing, sitting, and supine positions, each lasting 10 min. Detailed analyses of QT/RR profiles confirmed the absence of prolonged individually corrected QTc interval in each child. Heart rate and QT intervals were measured in 10-s ECG segments and in each segment, QTc intervals were obtained using Bazett, Fridericia, and Framingham formulas. In each child, the heart rates and QTc values obtained during supine, sitting and standing positions were averaged. QTc durations by the three formulas were classified to < 440 ms, 440-460 ms, 460-480 ms, and > 480 ms. RESULTS: At supine position, averaged heart rate was 77.5 ± 10.5 beat per minute (bpm) and Bazett, Fridericia and Framingham QTc intervals were 425.3 ± 15.8, 407.8 ± 13.9, and 408.2 ± 13.1 ms, respectively. At sitting and standing, averaged heart rate increased to 90.9 ± 10.1 and 100.9 ± 10.5 bpm, respectively. While Fridericia and Framingham formulas showed only minimal QTc changes, Bazett correction led to QTc increases to 435 ± 15.1 and 444.9 ± 15.9 ms at sitting and standing, respectively. At sitting, Bazett correction identified 51, 4, and 0 children as having the QTc intervals 440-460, 460-480, and > 480 ms, respectively. At sitting, these numbers increased to 118, 11, and 1, while on standing these numbers were 151, 45, and 5, respectively. Irrespective of the postural position, Fridericia and Framingham formulas identified only a small number (< 7) of children with QT interval between 440 and 460 ms and no children with longer QTc. CONCLUSION: During screening for LQTS in children, the use of Bazett formula leads to a high number of false positive cases especially if the heart rates are increased (e.g. by postural manoeuvring). The use of Fridericia formula can be recommended to replace the Bazett correction not only for adult but also for paediatric ECGs.

The potential of electrocardiography for cardiac risk prediction in chronic and end-stage kidney disease.

Cardiovascular mortality is very high in chronic and end-stage kidney disease (ESKD). However, risk stratification data are lacking. Sudden cardiac deaths are among the most common cardiovascular causes of death in these populations. As a result, many studies have assessed the prognostic potential of various electrocardiographic parameters in the renal population. Recent data from studies of implantable loop recordings in haemodialysis patients from five different countries have shed light on a pre-eminent bradyarrhythmic risk of mortality. Importantly, heart block addressed by permanent pacing system was detected in a proportion of patients during the prolonged recording periods. Standard electrocardiogram is inexpensive, non-invasive and easily accessible. Hence, risk prediction models using this simple investigation tool could easily translate into clinical practice. We believe that electrocardiographic assessment is currently under-valued in renal populations. For this review, we identified studies from the preceding 10 years that assessed the use of conventional and novel electrocardiographic biomarkers as risk predictors in chronic and ESKD. The review indicates that conventional electrocardiographic markers are not reliable for risk stratification in the renal populations. Novel parameters have shown promising results in smaller studies, but further validation in larger populations is required.

Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project.

BACKGROUND: The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue. SUMMARY: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, and first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12­lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit. CONCLUSION: The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular.

Clinical value of different QRS-T angle expressions.

Aims: Increased spatial angle between QRS complex and T wave loop orientations has repeatedly been shown to predict cardiac risk. However, there is no consensus on the methods for the calculation of the angle. This study compared the reproducibility and predictive power of three most common ways of QRS-T angle assessment. Methods and results: Electrocardiograms of 352 healthy subjects, 941 survivors of acute myocardial infarction (MI), and 605 patients recorded prior to the implantation of automatic defibrillator [implantable cardioverter defibrillator (ICD)] were used to obtain QRS-T angle measurements by the maximum R to T (MRT), area R to T (ART), and total cosine R to T (TCRT) methods. The results were compared in terms of physiologic reproducibility and power to predict mortality in the cardiac patients during 5-year follow-up. Maximum R to T results were significantly less reproducible compared to the other two methods. Among both survivors of acute MI and ICD recipients, TCRT method was statistically significantly more powerful in predicting mortality during follow-up. Among the acute MI survivors, increased spatial QRS-T angle (TCRT assessment) was particularly powerful in predicting sudden cardiac death with the area under the receiver operator characteristic of 78% (90% confidence interval 63-90%). Among the ICD recipients, TCRT also predicted mortality significantly among patients with prolonged QRS complex duration when the spatial orientation of the QRS complex is poorly defined. Conclusion: The TCRT method for the assessment of spatial QRS-T angle appears to offer important advantages in comparison to other methods of measurement. This approach should be included in future clinical studies of the QRS-T angle. The TCRT method might also be a reasonable candidate for the standardization of the QRS-T angle assessment.

Association of QRS-T angle and heart rate variability with major cardiac events and mortality in hemodialysis patients.

INTRODUCTION: Mortality in hemodialysis (HD) patients is high with significant proportion attributed to fatal arrhythmias. In a pilot study, we showed that intradialytic electrocardiographic (ECG) monitoring can yield stable profiles of selected repolarisation descriptors and heart rate variability (HRV) parameters. This study investigated the relationship of these ECG markers with major adverse cardiac events (MACE) and mortality. METHODS: Continuous ECGs were obtained during HD and repeated five times at 2-week intervals. The QRS-T angle calculated as Total Cosine R to T (TCRT) and T-wave morphology dispersion (TMD) were calculated in overlapping 10 s ECG segments. High- (HF) and low (LF)-frequency components and the LF/HF ratio of HRV were calculated every 5 min. These indices were averaged during the first hour of dialysis and subsequently overall recordings in each subject. RESULTS: All ECG parameters were available in 72 patients aged 61 ± 15, 23 (31.9%) females and 26 (36.1%) diabetics. After a median follow up of 54.8 months, 16 patients died, 20 were transplanted, and 9 suffered MACE. TCRT (in degrees) was higher and LF/HF was lower in patients who died compared to survivors (112 ± 30 vs. 73 ± 35, p = 0.000 and 0.222 ± 0.418 vs. 0.401 ± 0.274, p = 0.000, respectively) and in MACE positive compared to negative (117 ± 40 vs. 77 ± 34, p = 0.017 and 0.125 ± 0.333 vs.0.401 ± 0.274, p = 0.007 respectively). In multivariate Cox regression analysis of mortality risk adjusted for age, diabetes mellitus, and coronary artery disease, TCRT and LF/HF remained significant predictors (p < 0.05). CONCLUSION: QRS-T angle and HRV may serve risk assessment in future prospective studies in HD patients.

Importance of QT/RR hysteresis correction in studies of drug-induced QTc interval changes.

QT/RR hysteresis and QT/RR adaptation are interlinked but separate physiological processes signifying how quickly and how much QT interval changes when heart rate changes, respectively. While QT interval duration is, as a rule, corrected for heart rate in terms of the QT/RR adaptation, the correction for QT/RR hysteresis is frequently omitted in studies of drug-induced QTc changes. This study used data from previously conducted thorough QT studies to investigate the extent of QTc errors caused by omitting the correction for QT/RR hysteresis, particularly in small clinical investigations. Statistical modeling approach was used to generate 11,000 simulated samples of 10-subject studies in which mixed effect PK/PD models were used to estimate drug-induced QTc changes at mean maximum plasma concentration of investigated compounds. Calculations of QTc intervals involving and omitting QT/RR hysteresis correction were compared. These comparisons showed that ignoring QT/RR hysteresis has two undesirable effects: (A) In the design of subject-specific heart rate corrections (needed in studies of drugs that change heart rate) omission of QT/RR hysteresis may lead to signals of QTc prolongation of more than 10 ms to be missed. (B) Irrespective of whether the investigated drug changes heart rate, omission of QT/RR hysteresis causes the widths of the confidence intervals of the PK/PD predicted QTc interval changes to be increased by 20-30% on average (exceeding 50% in some cases). This may lead to a failure of excluding meaningful QTc prolongation which would be excluded if using hysteresis correction. The study concludes that correction for QT/RR hysteresis should be incorporated into future studies of drug-induced QTc changes. Subject-specific heart rate corrections that omit hysteresis correction may lead to erroneously biased conclusions. Even when using universal (e.g. Fridericia) heart rate correction, hysteresis correction decreases the confidence intervals of QTc changes and thus helps avoiding false positive outcomes.

Automation bias in medicine: The influence of automated diagnoses on interpreter accuracy and uncertainty when reading electrocardiograms.

INTRODUCTION: Interpretation of the 12­lead Electrocardiogram (ECG) is normally assisted with an automated diagnosis (AD), which can facilitate an 'automation bias' where interpreters can be anchored. In this paper, we studied, 1) the effect of an incorrect AD on interpretation accuracy and interpreter confidence (a proxy for uncertainty), and 2) whether confidence and other interpreter features can predict interpretation accuracy using machine learning. METHODS: This study analysed 9000 ECG interpretations from cardiology and non-cardiology fellows (CFs and non-CFs). One third of the ECGs involved no ADs, one third with ADs (half as incorrect) and one third had multiple ADs. Interpretations were scored and interpreter confidence was recorded for each interpretation and subsequently standardised using sigma scaling. Spearman coefficients were used for correlation analysis and C5.0 decision trees were used for predicting interpretation accuracy using basic interpreter features such as confidence, age, experience and designation. RESULTS: Interpretation accuracies achieved by CFs and non-CFs dropped by 43.20% and 58.95% respectively when an incorrect AD was presented (p < 0.001). Overall correlation between scaled confidence and interpretation accuracy was higher amongst CFs. However, correlation between confidence and interpretation accuracy decreased for both groups when an incorrect AD was presented. We found that an incorrect AD disturbs the reliability of interpreter confidence in predicting accuracy. An incorrect AD has a greater effect on the confidence of non-CFs (although this is not statistically significant it is close to the threshold, p = 0.065). The best C5.0 decision tree achieved an accuracy rate of 64.67% (p < 0.001), however this is only 6.56% greater than the no-information-rate. CONCLUSION: Incorrect ADs reduce the interpreter's diagnostic accuracy indicating an automation bias. Non-CFs tend to agree more with the ADs in comparison to CFs, hence less expert physicians are more effected by automation bias. Incorrect ADs reduce the interpreter's confidence and also reduces the predictive power of confidence for predicting accuracy (even more so for non-CFs). Whilst a statistically significant model was developed, it is difficult to predict interpretation accuracy using machine learning on basic features such as interpreter confidence, age, reader experience and designation.

Adiponectin, biomarkers of inflammation and changes in cardiac autonomic function: Whitehall II study.

BACKGROUND: Biomarkers of inflammation and adiponectin are associated with cardiovascular autonomic neuropathy (CAN) in cross-sectional studies, but prospective data are scarce. This study aimed to assess the associations of biomarkers of subclinical inflammation and adiponectin with subsequent changes in heart rate (HR) and heart rate variability (HRV) in non-diabetic and diabetic individuals. METHODS: Data are based on up to 25,050 person-examinations for 8469 study participants of the Whitehall II cohort study. Measures of CAN included HR and several HRV indices. Associations between baseline serum levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-1 receptor antagonist (IL-1Ra) and adiponectin and 5-year changes in HR and six HRV indices were estimated using mixed-effects models adjusting for age, sex, ethnicity, body mass index (BMI), metabolic covariates and medication. A modifying effect of diabetes was tested. RESULTS: Higher levels of IL-1Ra were associated with higher increases in HR. Additional associations with measures of HRV were observed for hsCRP, IL-6 and IL-1Ra, but these associations were explained by BMI and other confounders. Associations between adiponectin, HR and HRV differed depending on diabetes status. Higher adiponectin levels were associated with more pronounced decreases in HR and increases in three measures of HRV reflecting both sympathetic and vagal activity, but these findings were limited to individuals with type 2 diabetes. CONCLUSIONS: Higher IL-1Ra levels appeared as novel risk marker for increases in HR. Higher adiponectin levels were associated with a more favourable development of cardiovascular autonomic function in individuals with type 2 diabetes independently of multiple confounders.

Inappropriate ICD shocks do not induce pro-arrhythmic electrocardiographic changes in men.

OBJECTIVES: Longer-term electrocardiographic effects of multiple inappropriate ICD shocks were investigated to study their hypothesized pro-arrhythmic potential. DESIGN: Thirteen male patients with ischemic cardiomyopathy who received ≥2 inappropriate shocks within 24 h and for whom 12-lead ECGs were available both before and within 72h after the inappropriate shocks were analyzed. Exclusion criteria included continuous ventricular pacing, underlying AF, events within 6 weeks after lead implantation and concomitant acute medical problems. RESULTS: A total of 149 inappropriate shocks (mean 11 ± 19) were received. There were no significant differences in any of the measured intervals or morphological indices, nor was there a correlation between the "before-after" differences and the number of shocks received. Non-significant changes showed Percentage of Loop Area increase and relative T-wave Residuum decrease while the opposite changes have previously been associated with arrhythmic risk. CONCLUSIONS: No potentially pro-arrhythmic electrocardiographic changes were found 19 h after multiple inappropriate shocks.

Heart rate dependency of JT interval sections.

BACKGROUND: Little experience exists with the heart rate correction of J-Tpeak and Tpeak-Tend intervals. METHODS: In a population of 176 female and 176 male healthy subjects aged 32.3±9.8 and 33.1±8.4years, respectively, curve-linear and linear relationship to heart rate was investigated for different sections of the JT interval defined by the proportions of the area under the vector magnitude of the reconstructed 3D vectorcardiographic loop. RESULTS: The duration of the JT sub-section between approximately just before the T peak and almost the T end was found heart rate independent. Most of the JT heart rate dependency relates to the beginning of the interval. The duration of the terminal T wave tail is only weakly heart rate dependent. CONCLUSIONS: The Tpeak-Tend is only minimally heart rate dependent and in studies not showing substantial heart rate changes does not need to be heart rate corrected. For any correction formula that has linear additive properties, heart rate correction of JT and JTpeak intervals is practically the same as of the QT interval. However, this does not apply to the formulas in the form of Int/RRa since they do not have linear additive properties.

Sex and race differences in QRS duration.

AIMS: The study investigated healthy subjects to study sex and race differences in QRS durations and the dependency of QRS durations on heart rates and other physiologic correlates. METHODS AND RESULTS: QRS duration and its heart rate dependency were evaluated in 420 615 electrocardiograms obtained in 523 healthy subjects including 111 females of African origin, 130 Caucasian females, 125 males of African origin, and 129 Caucasian males. The distributions of QRS/RR slopes and QRS durations at RR intervals of 1 and 0.5 s were compared between sex- and race-defined subgroups. At high heart rates, QRS duration was increased in ∼35% of all subjects, while in the others, QRS was shortened (no differences between the subgroups). At RR interval of 1 s, the QRS duration was 97.4 ± 4.6, 99.8 ± 6.0, 101.6 ± 5.3, and 104.8 ± 6.3 ms in African females, Caucasian females, African males, and Caucasian males, respectively (all differences P < 0.001). Similar statistical differences were found at an RR of 0.5 s. When accounting for the differences in lean body mass, the difference between African and Caucasian subjects was as large as the difference between females and males. Within each subgroup, the normal QRS durations differed by 15-20 and 18-25 ms at RR intervals of 1 and 0.5 s, respectively. CONCLUSION: The QRS widths are heart rate dependent and different not only between women and men but also between African and Caucasian individuals. Difference in cardiac resynchronization therapy efficacy might be expected between patients of African and Caucasian origin stratified by QRS duration.

QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology.

This consensus guideline discusses the electrocardiographic phenomenon of beat-to-beat QT interval variability (QTV) on surface electrocardiograms. The text covers measurement principles, physiological basis, and clinical value of QTV. Technical considerations include QT interval measurement and the relation between QTV and heart rate variability. Research frontiers of QTV include understanding of QTV physiology, systematic evaluation of the link between QTV and direct measures of neural activity, modelling of the QTV dependence on the variability of other physiological variables, distinction between QTV and general T wave shape variability, and assessing of the QTV utility for guiding therapy. Increased QTV appears to be a risk marker of arrhythmic and cardiovascular death. It remains to be established whether it can guide therapy alone or in combination with other risk factors. QT interval variability has a possible role in non-invasive assessment of tonic sympathetic activity.