The Wolff-Parkinson-White pattern in neonates: results from a large population-based cohort study.

AIMS: Wolff-Parkinson-White (WPW) syndrome is a conduction disorder characterized by an accessory electrical pathway between the atria and ventricles, which may predispose to supraventricular tachycardia (SVT) and sudden cardiac death. It can be seen as an isolated finding or associated with structural heart disease. Our aims were to determine the prevalence of a WPW pattern in a large and unselected cohort of neonates and to describe the electro- and echocardiographic characteristics as well as the natural history during early childhood. METHODS AND RESULTS: Electrocardiograms and echocardiograms of neonates (aged 0-30 days) from a large, prospective, population-based cohort study were included. Neonates with a WPW pattern were identified and matched 1:4 to controls. Localization of the accessory pathway was assessed by different algorithms. Among 17 489 neonates, we identified 17 (76% boys) with a WPW pattern consistent with a prevalence of 0.1%. One neonate had moderate mitral regurgitation while other echocardiographic parameters were similar between cases and controls (all P > 0.05). The accessory pathways were primarily predicted to be left-sided. At follow-up (available in 14/17 children; mean age 3.2 years) the pre-excitation pattern persisted in only four of the children and none of the children had experienced any episodes of SVT. CONCLUSION: The prevalence of a WPW pattern in our cohort of unselected neonates was 0.1%. The WPW pattern was more frequent in boys and generally not associated with structural heart disease, and the accessory pathways were primarily left-sided. At follow-up, the WPW pattern had disappeared in most of the children suggesting either an intermittent nature or that normalization occurs. CLINICAL TRIAL REGISTRATION: Copenhagen Baby Heart, NCT02753348.

Electrocardiographic characteristics of newborns with ventricular septal defects: a Copenhagen Baby Heart Study.

Ventricular septal defects (VSD) represent the most common congenital heart defect in newborns. We assessed the electrocardiographic characteristics of newborns with VSDs in a general population sample. The Copenhagen Baby Heart Study is a prospective population-based cohort study offering cardiac evaluation of newborns. Echocardiograms and electrocardiograms were obtained within 30 days after birth and systematically analysed. A VSD was identified in 530 newborns (mean age 11 ± 7 days, 42% boys). Newborns with VSDs had a more left-shifted QRS axis (116 ± 34 vs. 120 ± 3°, p = 0.02), and a higher S-wave amplitude in V1 (721 ± 584 vs. 636 ± 549 µV, p = 0.001) than controls. The largest differences were found in newborns with large or perimembraneous VSDs with a higher frequency of left axis deviation, higher S-wave amplitudes in V1, and higher R- and S-wave amplitudes in V6 compared with controls. R-waves in V1 and V6 were significantly associated to left ventricular mass, whereas S-waves in V1 and V6 were dependent on left ventricular end-diastolic diameter on echocardiography.  Conclusion: Newborns with VSDs showed significant differences in QRS axis, and R- and S-wave precordial amplitudes compared to matched controls. Perimembranous and large VSDs had the greatest effect on the neonatal ECG. What is Known: • Ventricular septal defects in newborns are prevalent and may affect cardiac function and structure. What is New: • The Copenhagen Baby Heart Study is the largest study including a cohort of unselected newborns undergoing postnatal cardiac examination. • We found that newborns with VSD showed significant electrocardiographic differences depending on size and type of VSD compared with healthy newborns.

Cardiac findings in newborn twins.

AIMS: To evaluate cardiac findings in newborn twins from the general population and investigate if newborn twins may require systematic evaluation of cardiac parameters. METHODS: Prospective cohort study of newborns with cardiac evaluation performed during the first month of life. Cardiac findings were compared 1:3 with matched singletons. RESULTS: We included 412 newborn twins (16% monochorionic; 50% boys) and 1236 singletons. Comparing cardiac findings showed twins had an increased prevalence of non-severe structural heart disease (most common: ventricular septal defects in both groups), thinner left ventricular posterior wall in diastole (LVPWd; 1.82 vs. 1.87 mm, p = 0.02), smaller diameter of the left atrium (10.6 vs. 11.1 mm, p = 0.04), higher heart rate (148 vs. 144 bpm, p = 0.04), more left-shifted QRS axis (106 vs. 111°, p < 0.001), and lower maximum R-wave amplitude in V1 (927 vs. 1015 µV, p = 0.02) compared to singletons. After multifactorial adjustment for potential confounders, the effect of twinning on cardiac parameters persisted only for LVPWd (p < 0.05). CONCLUSION: Despite contemporary surveillance, we found an increased prevalence of non-severe structural heart disease in a population-based cohort of newborn twins. However, the effect of twinning on cardiac parameters was modest and generally did not persist after correction for likely confounding factors.

Associations between primary care electrocardiography and non-Alzheimer dementia.

OBJECTIVES: To determine whether electrocardiogram (ECG) markers are associated with incident non-Alzheimer's dementia (non-AD) and whether these markers also improve risk prediction for non-AD. MATERIALS AND METHODS: We retrospectively included 170,605 primary care patients aged 60 years or older referred for an ECG by their general practitioner and followed them for a median of 7.6 years. Using Cox regression, we reported hazard ratios (HRs) for electrocardiogram markers. Subsequently, we evaluated if addition of these electrocardiogram markers to a clinical model improved risk prediction for non-AD using change in area under the receiver-operator characteristics curve (AUC). RESULTS: The 5-year cumulative incidence of non-AD was 3.4 %. Increased heart rate (HR=1.06 pr. 10 bpm [95% confidence interval: 1.04-1.08], p<0.001), shorter QRS duration (HR=1.07 pr. 10 ms [1.05-1.09], p<0.001), elevated J-amplitude (HR=1.16 pr. mm [1.08-1.24], p<0.001), decreased T-peak amplitude (HR=1.02 pr. mm [1.01-1.04], p=0.002), and increased QTc (HR=1.08 pr. 20 ms [1.05-1.10], p<0.001) were associated with an increased rate of non-AD. Atrial fibrillation on the ECG (HR=1.18 [1.08-1.28], p<0.001) Sokolow-Lyon index > 35 mm (HR=1.31 [1.18-1.46], p<0.001) and borderline (HR=1.18 [1.11-1.26], p<0.001) or abnormal (HR=1.40 [1.27-1.55], p<0.001) QRS-T angle were also associated with an increased rate of non-AD. Upon addition of ECG markers to the Cox model, 5-year and 10-year C-statistic (AUC) improved significantly (delta-AUC, 0.36 [0.18-0.50] and 0.20 [0.03-0.35] %-points, respectively). CONCLUSIONS: ECG markers typical of an elevated cardiovascular risk profile were associated with non-AD and improved both 5-year and 10-year risk predictions for non-AD.

Defining the normal QT interval in newborns: the natural history and reference values for the first 4 weeks of life.

AIMS: Evaluation of the neonatal QT interval is important to diagnose arrhythmia syndromes and evaluate side effects of drugs. We aimed at describing the natural history of the QT interval duration during the first 4 weeks of life and to provide reference values from a large general population sample. METHODS AND RESULTS: The Copenhagen Baby Heart Study is a prospective general population study that offered cardiac evaluation of newborns. Eight-lead electrocardiograms were obtained and analysed with a computerized algorithm with manual validation. We included 14 164 newborns (52% boys), aged 0-28 days, with normal echocardiograms. The median values (ms, 2-98%ile) for the corrected intervals QTc (Bazett), QTc (Hodges), QTc (Fridericia), and QTc (Framingham) were 419 (373-474), 419 (373-472), 364 (320-414), and 363 (327-405). During the 4 weeks, we observed a small decrease of QTcFramingham, and an increase of QTcHodges (both P < 0.01), while QTcBazett and QTcFridericia did not change (P > 0.05). Applying published QT interval cut-off values resulted in 5-25% of the newborns having QT prolongation. Uncorrected QT intervals decreased linearly with increasing heart rate (HR). Sex and infant size did not affect the QT interval and the gestational age (GA) only showed an effect when comparing the extreme low- vs. high GA groups (≤34 vs. ≥42 weeks, P = 0.021). CONCLUSION: During the 4 weeks QTcFramingham and QTcHodges showed minor changes, whereas QTcBazett and QTcFridericia were stable. The QT interval was unaffected by sex and infant size and GA only showed an effect in very premature newborns. Reference values for HR-specific uncorrected QT intervals may facilitate a more accurate diagnosis of newborns with abnormal QT intervals.

Association between vectorcardiographic QRS area and incident heart failure diagnosis and mortality among patients with left bundle branch block: A register-based cohort study.

BACKGROUND: QRS duration and morphology including left bundle branch block (LBBB) are the most widely used electrocardiogram (ECG) markers for assessing ventricular dyssynchrony and predicting heart failure (HF). However, the vectorcardiographic QRS area may more accurately identify delayed left ventricular activation and HF development. OBJECTIVE: We investigated the association between QRS area and incident HF risk in patients with LBBB. METHODS: By crosslinking data from Danish nationwide registries, we identified patients with a first-time digital LBBB ECG between 2001 and 2015. The vectorcardiographic QRS area was derived from a 12­lead ECG using the Kors transformation method and grouped into quartiles. The endpoint was a composite of HF diagnosis, filled prescriptions for loop diuretics, or death from HF. Cause-specific multivariable Cox regression was used to compute hazard ratios(HR) with 95% confidence intervals(CI). RESULTS: We included 3316 patients with LBBB free from prior HF-related events (median age, 72 years; male, 40%). QRS area quartiles comprised Q1, 36-98 µVs; Q2, 99-119 µVs; Q3, 120-145 µVs; and Q4, 146-295 µVs. During a 5-year follow-up, 31% of patients reached the composite endpoint, with a rate of 39% in the highest quartile Q4. A QRS area in quartile Q4 was associated with increased hazard of the composite endpoint (HR:1.48, 95%CI:1.22-1.80) compared with Q1. CONCLUSIONS: Among primary care patients with newly discovered LBBB, a large vectorcardiographic QRS area (146-295 µVs) was associated with an increased risk of incident HF diagnosis, filling prescriptions for loop diuretics, or dying from HF within 5-years.

Precordial ECG Amplitudes in the Days After Birth: Electrocardiographic Changes During Transition from Fetal to Neonatal Circulation.

During the first month of life, the relation between right and left ventricular function is markedly altered. We aimed at describing the electrocardiographic transition from fetal to neonatal circulation by investigating changes in R- and S-wave amplitudes in V1 and V6 during the first 4 weeks of life. This study is part of the prospective, population-based Copenhagen Baby Heart Study offering cardiac evaluation to newborns within 28 days from birth. ECGs were obtained and analyzed using a computerized algorithm. A total of 14,577 newborns (52% boys), median age of 11.0 days, were included. All had normal echocardiograms. Within 28 days from birth, the amplitudes in V1 decreased: R-V1 (1262 µV day0; 947 µV day28, p < 0.001) and S-V1 (1240 µV day0; 473 µV day28, p < 0.001). An increase was observed for R-V6 (825 µV day0; 1196 µV day28, p = 0.002), while S-V6 decreased (830 µV day0; 634 µV day28, p = 0.003). For all amplitudes, interindividual variation was large (up to 20 times). The amplitudes were not affected by sex (p > 0.05), but R-V1, R-V6, and S-V6 positively correlated with newborn weight (p < 0.01). R-V1 and S-V6 showed positive correlation with gestational age (p < 0.05). In conclusion, systematic analyses of ECGs from healthy newborns showed significant decreases in R-V1, S-V1, and S-V6 amplitudes, while R-V6 increased. Interindividual variation was large, making ECGs unlikely as a sensitive tool for diagnosing congenital heart diseases. Our data may serve as updated, digitalized reference values in newborns.

Association between T-wave discordance and the development of heart failure in left bundle branch block patients: Results from the Copenhagen ECG study.

BACKGROUND: In left bundle branch block (LBBB), discrepancies between depolarization and repolarization of the heart can be assessed by similar direction (concordant) or opposite direction (discordant) of the lateral T-waves compared to the direction of the QRS complex and by the QRS-T angle. We examined the association between discordant T-waves and high QRS-T angles for heart failure development in primary care LBBB patients. METHODS: Between 2001 and 2011, we identified 2540 patients from primary care with LBBB without overt heart failure. We examined the development of heart failure in relation to two ECG measures: (1) LBBB as either discordant (two or three monophasic T-waves in the opposite direction of the QRS complex in leads I, V5 or V6) or concordant, and (2) the frontal plane QRS-T angle in quartile groups. RESULTS: In total, 244 of 913 patients (26.7%) with discordant LBBB developed heart failure compared to 302 of 1627 patients (16.7%) with concordant LBBB. Multivariable Cox regression comparing discordant with concordant LBBB showed a hazard ratio (HR) of 2.58 (95% Confidence interval [CI] 1.71-3.89) for heart failure development within 30 days of follow-up and a HR of 1.45 (95%CI 1.19-1.77) after 30 days. For QRS-T angle, comparing the highest quartile (160°-180°) with the lowest quartile (0°-110°) we found a HR of 2.25 (95%CI 1.26-4.02) within 30 days and a HR of 1.67 (95%CI 1.25-2.23) after 30 days. CONCLUSION: T-wave discordance in lateral ECG leads and a high QRS-T angle are associated with heart failure development in primary care LBBB patients.

The relationship between serum potassium concentrations and electrocardiographic characteristics in 163,547 individuals from primary care.

AIMS: Potassium disturbances are common and associated with increased morbidity and mortality, even in patients without prior cardiovascular disease. We examined six electrocardiographic (ECG) measures and their association to serum potassium levels. METHODS AND RESULTS: From the Copenhagen General Practitioners' Laboratory, we identified 163,547 individuals aged ≥16 years with a first available ECG and a concomitant serum potassium measurement during 2001-2011. Restricted cubic splines curves showed a non-linear relationship between potassium and the Fridericia corrected QT (QTcF) interval, T-wave amplitude, morphology combination score (MCS), PR interval, P-wave amplitude and duration. Therefore, potassium was stratified in two intervals K: 2.0-4.1 mmol/L and 4.2-6.0 mmol/L for further analyses. Within the low potassium range, we observed: QTcF was 12.8 ms longer for each mmol/L decrease in potassium (p < 0.0001); T-wave amplitude was 43.1 µV lower for each mmol/L decrease in potassium (p < 0.0001); and MCS was 0.13 higher per mmol/L decrease in potassium (p < 0.001). Moreover, P-wave duration and PR interval were prolonged by 2.7 and 4.6 ms for each mmol/L decrease in potassium (p < 0.0001), respectively. Within the lowest potassium range (2.0-4.1 mmol/L) P-wave amplitude was 3.5 µV higher for each mmol/L decrease in potassium (p < 0.0001). Within the high potassium range associations with the above-mentioned ECG parameters were much weaker.

Risk prediction of cardiovascular death based on the QTc interval: evaluating age and gender differences in a large primary care population.

AIMS: Using a large, contemporary primary care population we aimed to provide absolute long-term risks of cardiovascular death (CVD) based on the QTc interval and to test whether the QTc interval is of value in risk prediction of CVD on an individual level. METHODS AND RESULTS: Digital electrocardiograms from 173 529 primary care patients aged 50-90 years were collected during 2001-11. The Framingham formula was used for heart rate-correction of the QT interval. Data on medication, comorbidity, and outcomes were retrieved from administrative registries. During a median follow-up period of 6.1 years, 6647 persons died from cardiovascular causes. Long-term risks of CVD were estimated for subgroups defined by age, gender, cardiovascular disease, and QTc interval categories. In general, we observed an increased risk of CVD for both very short and long QTc intervals. Prolongation of the QTc interval resulted in the worst prognosis for men whereas in women, a very short QTc interval was equivalent in risk to a borderline prolonged QTc interval. The effect of the QTc interval on the absolute risk of CVD was most pronounced in the elderly and in those with cardiovascular disease whereas the effect was negligible for middle-aged women without cardiovascular disease. The most important improvement in prediction accuracy was noted for women aged 70-90 years. In this subgroup, a total of 9.5% were reclassified (7.2% more accurately vs. 2.3% more inaccurately) within clinically relevant 5-year risk groups when the QTc interval was added to a conventional risk model for CVD. CONCLUSION: Important differences were observed across subgroups when the absolute long-term risk of CVD was estimated based on QTc interval duration. The accuracy of the personalized CVD prognosis can be improved when the QTc interval is introduced to a conventional risk model for CVD.

Association between primary care electrocardiogram markers and Alzheimer's disease.

OBJECTIVE: The association between common electrocardiogram (ECG) markers and Alzheimer's disease has been scarcely investigated, and it is unknown if ECG markers can improve risk prediction. Thus, we aimed to examine the association between common ECG markers and Alzheimer's disease in a large population. METHODS: We studied the association between ECG markers and Alzheimer's disease using Cox models with adjustment for age, sex, and comorbidities using a large primary care population of patients aged 60 years or more. RESULTS: We followed 172,236 subjects for a median of 7.5 years. Increased PR interval (hazard ratio for PR > 188 ms: 0.76 [95% confidence interval: 0.69-0.83, p < 0.001) and increased QTc interval (hazard ratio for QTc = [426;439]: 0.90 [0.83-0.98], p = 0.02) were associated with a decreased rate of Alzheimer's disease. A positive Sokolow-Lyon index >35 mm (1.22 [1.13-1.33], p < 0.001) and increased T-wave amplitude >4.1 mm (1.15 [1.04-1.27]) were associated with an increased rate of Alzheimer's disease. Upon addition of ECG markers to a reference model, 10-year prediction area under the receiver-operator characteristics curve (AUC) improved by 0.39 [0.06-0.67] %-points. The 10-year absolute risk of Alzheimer's disease was 6.5% and 5.2% for an 82-year old female and a male, respectively, with a favorable ECG, and 12% and 9.2%, respectively, with an unfavorable ECG, almost twice as high. CONCLUSIONS: We identified several common ECG markers which were associated with Alzheimer's disease, and which improved risk prediction for Alzheimer's disease.

The Impact of Maternal Age on the Neonatal Electrocardiogram.

BACKGROUND: Previous studies have suggested an increased prevalence of congenital heart disease among children born to women aged ≥35 years. In recent decades, the mother's age at childbirth has increased dramatically in industrialized countries. It has not been investigated if increasing maternal age affects the neonatal cardiac electrical system. METHODS: The Copenhagen Baby Heart Study is a prospective general population study that performed cardiac evaluation in newborns. Electrocardiograms were analyzed with a computerized algorithm. RESULTS: We included 16,518 newborns with normal echocardiograms (median age 11 days; range 0-30 days; 52% boys). Median maternal age at delivery was 31 years; 790 newborns were born to mothers aged between 16 and 24 years, 11,403 between 25 and 34 years, 4,279 between 35 and 44 years, and 46 newborns had mothers aged between 45 and 54 years. The QRS axis and maximum R-wave amplitude in V1 (R-V1) differed across the four maternal age groups (both p < 0.01), with absolute differences of 3.5% (114 vs. 110°) and 12% (1,152 vs. 1,015 µV), respectively, between newborns with the youngest and oldest mothers. Associations between maternal age and the QRS axis and R-V1 remained significant after multifactorial adjustment. Heart rate, PR interval, QRS duration, uncorrected QT interval, QTcBazett, and maximum amplitudes of S-V1, R-V6, and S-V6 were not associated with maternal age (all p > 0.05). CONCLUSION: We observed a significant association between maternal age and the neonatal QRS axis and R-V1. However, the absolute differences were relatively small and maternal age is unlikely to have a clinically significant effect on the neonatal cardiac electrical system.

Electrocardiographic Findings, Arrhythmias, and Left Ventricular Involvement in Familial ST-Depression Syndrome.

BACKGROUND: Familial ST-depression syndrome is an inherited disease characterized by persistent, nonischemic ST-deviations, and risk of arrhythmias and heart failure. We aimed at further characterizing the ECG, arrhythmias, and structural characteristics associated with this novel syndrome. METHODS: Retrospective analysis of data from consecutive families with familial ST-depression Syndrome in Denmark. ECG features, prevalence and type of arrhythmias, occurrence of systolic dysfunction, and medium-term outcome were analyzed. RESULTS: Forty affected individuals (43% men; mean age at diagnosis 49.1 years) from 14 apparently unrelated families with ≥2 affected members were included. Autosomal dominant inheritance was observed in all families. The ECG phenotype seemed to develop in prepuberty and the ST-deviations were persistent and most pronounced in leads V4/V5/II, respectively. Serial ECG analyses showed stable to slow progression of the ECG phenotype. Exercise accentuated the ST-deviations with a maximum difference between rest/stress (mean) of -117 µV in lead V5. During a mean follow-up of 9.3±7.1 years 5 (13%) patients developed sustained ventricular arrhythmias or (aborted) sudden cardiac death, 10 (25%) developed atrial fibrillation, 2 (5%) other supraventricular arrhythmias, and 10 (25%) were diagnosed with left ventricular ejection fraction ≤50%. The ventricular arrhythmias were polymorphic with relatively short-coupled premature ventricular contractions at onset (300-360 ms); no QT prolongation was observed. Seven patients had at least one catheter ablation; 5 for supraventricular arrhythmias and 2 for ventricular arrhythmias. Males experienced more arrhythmic end points than females (P<0.01). CONCLUSIONS: The familial ST-depression ECG phenotype is stable to slowly progressive after medium-term follow-up. Clinically, both supra- and ventricular arrhythmias are common; as are some degree of left ventricular systolic dysfunction. Familial ST-depression represent a novel inherited cause of polymorphic ventricular tachycardia.

Fascicular heart blocks and risk of adverse cardiovascular outcomes: Results from a large primary care population.

BACKGROUND: Fascicular heart blocks can progress to complete heart blocks, but this risk has not been evaluated in a large general population. OBJECTIVE: The purpose of this study was to investigate the association between various types of fascicular blocks diagnosed by electrocardiographic (ECG) readings and the risk of incident higher degree atrioventricular block (AVB), syncope, pacemaker implantation, and death. METHODS: We studied primary care patients referred for ECG recording between 2001 and 2015. Cox regression models were used to estimate hazard ratios (HRs) as well as absolute risks of cardiovascular outcomes. RESULTS: Of 358,958 primary care patients (median age 54 years; 55% women), 13,636 (3.8%) had any type of fascicular block. Patients were followed up to 15.9 years. We found increasing HRs of incident syncope, pacemaker implantation, and third-degree AVB with increasing complexity of fascicular block. Compared with no block, isolated left anterior fascicular block (LAFB) was associated with 0%-2% increased 10-year risk of developing third-degree AVB (HR 1.6; 95% confidence interval [CI] 1.25-2.05), whereas right bundle branch block combined with LAFB and first-degree AVB was associated with up to 23% increased 10-year risk (HR 11.0; 95% CI 7.7-15.7), depending on age and sex group. Except for left posterior fascicular block (HR 2.09; 95% CI 1.87-2.32), we did not find any relevant associations between fascicular block and death. CONCLUSION: We found that higher degrees of fascicular blocks were associated with increasing risk of syncope, pacemaker implantation, and complete heart block, but the association with death was negligible.

Gestational Age and Neonatal Electrocardiograms.

OBJECTIVES: Interpretation of the neonatal electrocardiogram (ECG) is challenging due to the profound changes of the cardiovascular system in this period. We aimed to investigate the impact of gestational age (GA) on the neonatal ECG and create GA-specific reference values. METHODS: The Copenhagen Baby Heart Study is a prospective general population study that offered cardiac evaluation of neonates. ECGs and echocardiograms were obtained and systematically analyzed. GA, weight, height, and other baseline variables were registered. RESULTS: We included 16 462 neonates (52% boys) with normal echocardiograms. The median postnatal age was 11 days (range 0 to 30), and the median GA was 281 days (range 238 to 301). Analyzing the ECG parameters as a function of GA, we found an effect of GA on almost all investigated ECG parameters. The largest percentual effect of GA was on heart rate (HR; 147 vs 139 beats per minute), the QRS axis (103° vs 116°), and maximum R-wave amplitude in V1 (R-V1; 0.97 vs 1.19 mV) for GA ≤35 vs ≥42 weeks, respectively. Boys had longer PR and QRS intervals and a more right-shifted QRS axis within multiple GA intervals (all P < .01). The effect of GA generally persisted after multifactorial adjustment. CONCLUSIONS: GA was associated with significant differences in multiple neonatal ECG parameters. The association generally persisted after multifactorial adjustment, indicating a direct effect of GA on the developing neonatal cardiac conduction system. For HR, the QRS axis, and R-V1, the use of GA-specific reference values may optimize clinical handling of neonates.

The Evolution of the Neonatal QRS Axis during the First Four Weeks of Life.

BACKGROUND: The QRS axis represents the sum and orientation of the ventricular depolarization. Accurate interpretation of abnormalities in the QRS axis may facilitate early diagnosis of heart disease in newborns. We aimed at describing the evolution of the QRS axis during the first 4 weeks of life and provide reference values from healthy newborns. METHODS: The Copenhagen Baby Heart Study is a prospective general population study that offered cardiac evaluation during the first month of life to all newborns delivered in the Copenhagen area. RESULTS: Electrocardiograms from 12,317 newborns (52% boys; mean age 12 days) with normal echocardiograms were included. The median QRS axis was 119° at the ages 0-7 days and shifted leftward to 102° at the ages 22-28 days (p < 0.001). We found that girls had a significantly less pronounced right-shifted axis than boys (p < 0.001) and that increasing gestational age (GA) was associated with a more pronounced right-shifted axis (p < 0.05). Infant size did not affect the axis (p > 0.05). Only 0.5% had an axis within the interval 0 to -90° and 1.1% in the interval +240 to +30°. CONCLUSIONS: The QRS axis showed a gradual leftward-shift during the first 4 weeks of life and was affected by sex and GA but unaffected by infant size. Less than 1% of the newborns had a QRS axis between 0 and -90°. This study represents updated reference values, which may facilitate the clinical handling of newborns.

Electrocardiographic T-wave morphology and risk of mortality.

BACKGROUND: Electrocardiographic T-wave morphology is used in drug safety studies as an adjunct to the QTc interval, but few measurements of T-wave morphology can be interpreted in clinical practice. Morphology combination score (MCS) is a combination of T-wave flatness/peakedness, asymmetry, and notching, enabling easy visual assessment of T-wave morphology. We aimed to test the association between T-wave morphology, quantified by MCS, and mortality. METHODS: We included electrocardiograms recorded in 2001-2011 from 342,294 primary care patients. Using Cox regression, we evaluated the association between MCS, cardiovascular death, and all-cause mortality, adjusting for heart rate, QTc, QT-prolonging drugs, diabetes, ischemic heart disease, hypertension, and congestive heart failure. RESULTS: 270,039 individuals (44% men, median age 55 [inter-quartile range: 42-67 years]) were included and followed for a median of 9.3 years, during which time 13,489 (5.0%) died from cardiovascular causes and 50,481 (18.7%) from any cause. High values of MCS (i.e. asymmetric, flattened, and/or notched T waves) were associated with an adjusted mortality Hazard Ratio of 1.75 (95% CI 1.62-1.89) and 1.61 (1.43-1.92) for women and men, respectively. Low values of MCS (i.e. peaked and symmetric T waves) were associated with a Hazard Ratio of 1.18 (1.08-1.28) and 1.71 (1.48-1.98) for women and men, respectively. CONCLUSIONS: In a large primary care population, we found that T-wave asymmetry, flatness, and notching provided prognostic information on mortality independent of heart rate, QTc, and baseline comorbidities.

Association Between ECG Abnormalities and Fatal Cardiovascular Disease Among Patients With and Without Severe Mental Illness.

Background ECG abnormalities are associated with adverse outcomes in the general population, but their prognostic significance in severe mental illness (SMI) remains unexplored. We investigated associations between no, minor, and major ECG abnormalities and fatal cardiovascular disease (CVD) among patients with SMI compared with controls without mental illness. Methods and Results We cross-linked data from Danish nationwide registries and included primary care patients with digital ECGs from 2001 to 2015. Patients had SMI if they were diagnosed with schizophrenia, bipolar disorder, or severe depression before ECG recording. Controls were required to be without any prior mental illness or psychotropic medication use. Fatal CVD was assessed using hazard ratios (HRs) with 95% CIs and standardized 10-year absolute risks. Of 346 552 patients, 10 028 had SMI (3%; median age, 54 years; male, 45%), and 336 524 were controls (97%; median age, 56 years; male, 48%). We observed an interaction between SMI and ECG abnormalities on fatal CVD (P<0.001). Severe mental illness was associated with fatal CVD across no (HR, 2.17; 95% CI, 1.95-2.43), minor (HR, 1.90; 95% CI, 1.49-2.42), and major (HR, 1.40; 95% CI, 1.26-1.55) ECG abnormalities compared with controls. Across age- and sex-specific subgroups, SMI patients with ECG abnormalities but no CVD at baseline had highest standardized 10-year absolute risks of fatal CVD. Conclusions ECG abnormalities conferred a poorer prognosis among patients with SMI compared with controls without mental illness. SMI patients with ECG abnormalities but no CVD represent a high-risk population that may benefit from greater surveillance and risk management.

Associations between left bundle branch block with different PR intervals, QRS durations, heart rates and the risk of heart failure: a register-based cohort study using ECG data from the primary care setting.

AIM: Left bundle branch block (LBBB) is associated with an increased risk of heart failure (HF). We assessed the impact of common ECG parameters on this association using large-scale data. METHODS AND RESULTS: Using ECGs recorded in a large primary care population from 2001 to 2011, we identified HF-naive patients with a first-time LBBB ECG. We obtained information on sex, age, emigration, medication, diseases and death from Danish registries. We investigated the association between the PR interval, QRS duration, and heart rate and the risk of HF over a 2-year follow-up period using Cox regression analysis.Of 2471 included patients with LBBB, 464 (18.8%) developed HF during follow-up. A significant interaction was found between QRS duration and heart rate (p<0.01), and the analyses were stratified on these parameters. Using a QRS duration <150 ms and a heart rate <70 beats per minute (bpm) as the reference, all groups were statistically significantly associated with the development of HF. Patients with a QRS duration ≥150 ms and heart rate ≥70 bpm had the highest risk of developing HF (HR 3.17 (95% CI 2.41 to 4.18, p<0.001). There was no association between the PR interval and HF after adjustment. CONCLUSION: Prolonged QRS duration and higher heart rate were associated with increased risk of HF among primary care patients with LBBB, while no association was observed with PR interval. Patients with LBBB with both a prolonged QRS duration (≥150 ms) and higher heart rate (≥70 bpm) have the highest risk of developing HF.

Electrocardiogram Characteristics and Their Association With Psychotropic Drugs Among Patients With Schizophrenia.

BACKGROUND: There are limited data on electrocardiogram (ECG) characteristics and their association with psychotropic drugs in schizophrenia. METHODS: Using a cross-sectional design, we included Danish primary care patients with first-time digital ECGs from 2001 to 2015. Patients diagnosed with schizophrenia before ECG recording were matched 1:5 on age, sex, and ECG recording year to controls without psychiatric disease. Multivariable logistic regression was used to compute odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We included 4486 patients with schizophrenia matched with 22 430 controls (median age, 47 years; male, 55%). Between groups, the prevalence of abnormal ECGs was similar (54%, P = .536), but patients with schizophrenia demonstrated higher median heart rate (79 vs 69 beats per minute, P < .001) and Fridericia-corrected QT (QTc) interval (416 vs 412 ms, P < .001) than controls. QTc prolongation was also more prevalent among patients with schizophrenia (3.4% vs 1.1%, P < .001), and so were pathological Q waves (5.3% vs 3.9%, P < .001). Patients with schizophrenia less frequently demonstrated left ventricular hypertrophy (6.1% vs 9.6%, P < .001) and atrial fibrillation or flutter (0.7% vs 1.4%, P < .001). Among patients with schizophrenia only, particularly antipsychotics were associated with abnormal ECGs (OR, 1.20; 95% CI, 1.04-1.39). CONCLUSIONS: Patients with schizophrenia demonstrate a different cardiovascular risk profile than matched controls without psychiatric disease, with higher prevalence of elevated heart rate, QTc prolongation, and pathological Q waves, and lower prevalence of left ventricular hypertrophy and atrial fibrillation or flutter. Particularly antipsychotics were associated with abnormal ECGs. This underscores an integrated care approach when ECG abnormalities are detected in this group.