Publications by authors named "Adrian Pietersen"

29 Publications

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Gestational Age and Neonatal Electrocardiograms.

Pediatrics 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1542/peds.2021-050942DOI Listing
November 2021

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

Heart Rhythm 2021 Oct 19. Epub 2021 Oct 19.

Department of Cardiology, The Heart Centre, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Laboratory for Molecular Cardiology, The Heart Centre, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1016/j.hrthm.2021.09.041DOI Listing
October 2021

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

J Electrocardiol 2021 Nov-Dec;69:30-35. Epub 2021 Sep 4.

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Inova Heart and Vascular Institute, Fairfax, VA, United States.

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 12‑lead 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.
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http://dx.doi.org/10.1016/j.jelectrocard.2021.09.002DOI Listing
September 2021

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

Neonatology 2021 10;118(2):155-162. Epub 2021 Mar 10.

Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark,

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.
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http://dx.doi.org/10.1159/000513526DOI Listing
August 2021

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.

Open Heart 2021 02;8(1)

Department of Clinical Epidemiology, Aalborg University Hospital, Aalborg, Denmark.

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, p0.001). 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.
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http://dx.doi.org/10.1136/openhrt-2020-001425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880100PMC
February 2021

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

Pediatr Cardiol 2021 Apr 28;42(4):832-839. Epub 2021 Jan 28.

Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Danmark.

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.
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http://dx.doi.org/10.1007/s00246-021-02547-8DOI Listing
April 2021

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

J Am Heart Assoc 2021 01 12;10(2):e019416. Epub 2021 Jan 12.

Department of Cardiology Aalborg University Hospital Aalborg Denmark.

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 (<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.
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http://dx.doi.org/10.1161/JAHA.120.019416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955293PMC
January 2021

Electrocardiographic T-wave morphology and risk of mortality.

Int J Cardiol 2021 04 13;328:199-205. Epub 2020 Dec 13.

Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Background: Electrocardiographic T-wave morphology is used in drug safety studies as an adjunct to the QT 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, QT, 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.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.016DOI Listing
April 2021

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

Europace 2021 02;23(2):278-286

Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, DK-2730 Herlev, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1093/europace/euaa143DOI Listing
February 2021

Long-Term Prognostic Value of Less-Stringent Electrocardiographic Q Waves and Fourth Universal Definition of Myocardial Infarction Q Waves.

Am J Med 2020 05 21;133(5):582-589.e7. Epub 2019 Oct 21.

Unit of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark.

Background: The Fourth Universal Definition of Myocardial Infarction defines electrocardiographic Q waves as duration ≥30 ms and amplitude ≥1 mm or QS complex in 2 contiguous leads. However, current taskforce criteria may be overly restrictive. Therefore, we investigated the association of isolated, lenient, or strict Q waves with long-term outcome.

Methods: From 2001 to 2015, we included Danish primary care patients with digital electrocardiograms (ECGs) that were evaluated for Q waves. If none occurred, patients had no Q waves. If no other contiguous Q wave occurred, patients had isolated Q waves. If another contiguous Q wave occurred meeting only 1 criterion (≥30 ms and <1 mm or <30 ms and ≥1 mm), patients had lenient Q waves. If another contiguous Q wave occurred, patients had strict Q waves.

Results: Of 365,206 patients, 87,957 had isolated, lenient, or strict Q waves (24%; median age, 61 years; male, 48%), and 277,249 had no Q waves (76%; median age, 53 years; male, 42%). Mortality risk was increased with isolated (all-cause adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 1.29-1.37; cardiovascular-cause aHR, 1.78; 95% CI, 1.70-1.87), lenient (all-cause aHR, 1.41; 95% CI, 1.33-1.50; cardiovascular-cause aHR, 1.78; 95% CI, 1.63-1.94), or strict (all-cause aHR, 1.64; 95% CI, 1.57-1.72; cardiovascular-cause aHR, 2.70; 95% CI, 2.52-2.89) Q waves compared with no Q waves. Highest mortality risk was associated with lenient or strict Q waves in anteroseptal leads.

Conclusions: This large contemporary analysis suggests that less-stringent Q-wave criteria carry prognostic value in predicting adverse outcome among primary care patients.
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http://dx.doi.org/10.1016/j.amjmed.2019.08.056DOI Listing
May 2020

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

J Electrocardiol 2019 Nov - Dec;57:104-111. Epub 2019 Sep 4.

Unit of Epidemiology and Biostatistics, Aalborg University Hospital, Søndre Skovvej 15, 9000 Aalborg, Denmark.

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.
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http://dx.doi.org/10.1016/j.jelectrocard.2019.09.005DOI Listing
June 2021

Thyroid dysfunction and electrocardiographic changes in subjects without arrhythmias: a cross-sectional study of primary healthcare subjects from Copenhagen.

BMJ Open 2019 06 21;9(6):e023854. Epub 2019 Jun 21.

Department of Clinical Epidemiology, Aalborg University Hospital, Aalborg, Denmark.

Objective: The objective of the present study was to investigate associations of both overt and subclinical thyroid dysfunction with common ECG parameters in a large primary healthcare population.

Design: Cross-sectional study.

Setting And Participants: The study population comprised of primary healthcare patients in Copenhagen, Denmark, who had a thyroid function test and an ECG recorded within 7 days of each other between 2001 and 2011.

Data Sources: The Danish National Patient Registry was used to collect information regarding baseline characteristics and important comorbidities.

Outcome Measure And Study Groups: Common ECG parameters were determined using Marquette 12SL software and were compared between the study groups. The study population was divided into five groups based on their thyroid status. Euthyroid subjects served as the reference group in all analyses.

Results: A total of 132 707 patients (age 52±17 years; 50% female) were included. Hyperthyroidism was significantly associated with higher heart rate and prolonged QTc interval with significant interaction with age (p<0.009) and sex (p<0.001). These associations were less pronounced for patients with higher age. Subclinical hyperthyroidism was associated with higher heart rate among females, and a similar trend was observed among males. Hypothyroidism was associated with slower heart rate and shorter QTc but only in women. Moreover, longer P-wave duration, longer PR interval and low voltage were observed in patients with both subclinical and overt hypothyroidism. However, the presence of low voltage was less pronounced with higher age (p=0.001).

Conclusion: Both overt and subclinical thyroid disorders were associated with significant changes in important ECG parameters. Age and gender have significant impact on the association of thyroid dysfunction particularly on heart rate and QTc interval.
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http://dx.doi.org/10.1136/bmjopen-2018-023854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596967PMC
June 2019

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

Schizophr Bull 2020 02;46(2):354-362

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

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.
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http://dx.doi.org/10.1093/schbul/sbz064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442389PMC
February 2020

Associations between common ECG abnormalities and out-of-hospital cardiac arrest.

Open Heart 2019;6(1):e000905. Epub 2019 May 21.

Department of Clinical Epidemiology, Aalborg Universitetshospital, Aalborg, Denmark.

Background: Out-of-hospital cardiac arrest (OHCA) is often the first manifestation of unrecognised cardiac disease. ECG abnormalities encountered in primary care settings may be warning signs of OHCA.

Objective: We examined the association between common ECG abnormalities and OHCA in a primary care setting.

Methods: We cross-linked individuals who had an ECG recording between 2001 and 2011 in a primary care setting with the Danish Cardiac Arrest Registry and identified OHCAs of presumed cardiac cause.

Results: A total of 326 227 individuals were included and 2667 (0,8%) suffered an OHCA. In Cox regression analyses, adjusted for age and sex, the following ECG findings were strongly associated with OHCA: ST-depression without concomitant atrial fibrillation (HR 2.79; 95% CI 2.45 to 3.18), left bundle branch block (LBBB; HR 3.44; 95% CI 2.85 to 4.14) and non-specific intraventricular block (NSIB; HR 3.15; 95% CI 2.58 to 3.83). Also associated with OHCA were atrial fibrillation (HR 1.89; 95% CI 1.63 to 2.18), Q-wave (HR 1.75; 95% CI 1.57 to 1.95), Cornell and Sokolow-Lyon criteria for left ventricular hypertrophy (HR 1.56; 95% CI 1.33 to 1.82 and HR 1.27; 95% CI 1.12 to 1.45, respectively), ST-elevation (HR 1.40; 95% CI 1.09 to 1.54) and right bundle branch block (HR 1.29; 95% CI 1.09 to 1.54). The association between ST-depression and OHCA diminished with concomitant atrial fibrillation (HR 1.79; 95% CI 1.42 to 2.24, p < 0.01 for interaction). Among patients suffering from OHCA, without a known cardiac disease at the time of the cardiac arrest, 14.2 % had LBBB, NSIB or ST-depression.

Conclusions: Several common ECG findings obtained from a primary care setting are associated with OHCA.
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http://dx.doi.org/10.1136/openhrt-2018-000905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546195PMC
February 2021

Clinical implications of electrocardiographic bundle branch block in primary care.

Heart 2019 08 25;105(15):1160-1167. Epub 2019 May 25.

Laboratory for Molecular Cardiology, University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Objectives: Electrocardiographic bundle branch block (BBB) is common but the prognostic implications in primary care are unclear. We sought to investigate the relationship between electrocardiographic BBB subtypes and the risk of cardiovascular (CV) outcomes in a primary care population free of major CV disease.

Methods: Retrospective cohort study of primary care patients referred for electrocardiogram (ECG) recording between 2001 and 2011. Cox regression models were used to estimate hazard ratios (HR) as well as absolute risks of CV outcomes based on various BBB subtypes.

Results: We included 202 268 individuals with a median follow-up period of 7.8 years (Inter-quartile range [IQR] 4.9-10.6). Left bundle branch block (LBBB) was associated with heart failure (HF) in both men (HR 3.96, 95% CI 3.30 to 4.76) and women (HR 2.51, 95% CI 2.15 to 2.94) and with CV death in men (HR 1.80, 95% CI 1.38 to 2.35). Right bundle branch block (RBBB) was associated with pacemaker implantation in both men (HR 3.26, 95% CI 2.74 to 3.89) and women (HR 3.69, 95% CI 2.91 to 4.67), HF in both sexes and weakly associated with CV death in men. Regarding LBBB, we found an increasing hazard of HF with increasing QRS-interval duration (HR 1.25, 95% CI 1.11 to 1.42 per 10 ms increase in men and HR 1.23, 95% CI 1.08 to 1.40 per 10 ms increase in women). Absolute 10-year risk predictions across age-specific and sex-specific subgroups revealed clinically relevant differences between having various BBB subtypes.

Conclusions: Opportunistic findings of BBB subtypes in primary care patients without major CV disease should be considered warnings of future HF and pacemaker implantation.
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http://dx.doi.org/10.1136/heartjnl-2018-314295DOI Listing
August 2019

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

J Electrocardiol 2019 Jan - Feb;52:39-45. Epub 2018 Nov 5.

Unit of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark.

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.
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http://dx.doi.org/10.1016/j.jelectrocard.2018.11.001DOI Listing
April 2020

Risk Prediction of Atrial Fibrillation Based on Electrocardiographic Interatrial Block.

J Am Heart Assoc 2018 05 30;7(11). Epub 2018 May 30.

Laboratory for Molecular Cardiology, The Heart Center, Rigshospitalet University of Copenhagen, Denmark

Background: The electrocardiographic interatrial block (IAB) has been associated with atrial fibrillation (AF). We aimed to test whether IAB can improve risk prediction of AF for the individual person.

Methods And Results: Digital ECGs of 152 759 primary care patients aged 50 to 90 years were collected from 2001 to 2011. We identified individuals with P-wave ≥120 ms and the presence of none, 1, 2, or 3 biphasic P-waves in inferior leads. Data on comorbidity, medication, and outcomes were obtained from nationwide registries. We observed a dose-response relationship between the number of biphasic P-waves in inferior leads and the hazard of AF during follow-up. Discrimination of the 10-year outcome of AF, measured by time-dependent area under the curve, was increased by 1.09% (95% confidence interval 0.43-1.74%) for individuals with cardiovascular disease at baseline (CVD) and 1.01% (95% confidence interval 0.40-1.62%) for individuals without CVD, when IAB was added to a conventional risk model for AF. The highest effect of IAB on the absolute risk of AF was observed in individuals aged 60 to 70 years with CVD. In this subgroup, the 10-year risk of AF was 50% in those with advanced IAB compared with 10% in those with a normal P-wave. In general, individuals with advanced IAB and no CVD had a higher risk of AF than patients with CVD and no IAB.

Conclusions: IAB improves risk prediction of AF when added to a conventional risk model. Clinicians may consider monitoring patients with IAB more closely for the occurrence of AF, especially for high-risk subgroups.
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http://dx.doi.org/10.1161/JAHA.117.008247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015370PMC
May 2018

Electrocardiographic Preexcitation and Risk of Cardiovascular Morbidity and Mortality: Results From the Copenhagen ECG Study.

Circ Arrhythm Electrophysiol 2017 Jun;10(6)

From the Laboratory for Molecular Cardiology, The Heart Centre, Rigshospitalet, Copenhagen, Denmark (M.W.S., P.V.R., J.G., M.S.O., S.H., J.H.S., A.G.H., J.B.N.); Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (S.H., L.K., J.H.S.); Department of Health Science and Technology, Aalborg University, Denmark (S.M.H., C.G., C.T.-P.); Copenhagen General Practitioners' Laboratory, Denmark (A.P.); and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor (J.B.N.).

Background: The majority of available data on the clinical course of patients with ventricular preexcitation in the ECG originates from tertiary centers. We aimed to investigate long-term outcomes in individuals from a primary care population with electrocardiographic preexcitation.

Methods And Results: Digital ECGs from 328 638 primary care patients were collected during 2001 to 2011. We identified 310 individuals with preexcitation (age range, 8-85 years). Data on medication, comorbidity, and outcomes were collected from Danish nationwide registries. The median follow-up time was 7.4 years (quartiles, 4.6-10.3 years). Compared with the remainder of the population, patients with preexcitation had higher adjusted hazards of atrial fibrillation (hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.07-4.70) and heart failure (HR, 2.11; 95% CI, 1.27-3.50). Subgroup analysis on accessory pathway location revealed a higher adjusted hazard of heart failure for a right anteroseptal accessory pathway (HR, 5.88; 95% CI, 2.63-13.1). There was no evidence of a higher hazard of death among individuals with preexcitation when looking across all age groups (HR, 1.07; 95% CI, 0.68-1.68). However, a statistically significant (=0.01) interaction analysis (<65 versus ≥65 years) indicated a higher hazard of death for patients with preexcitation ≥65 years (HR, 1.85; 95% CI, 1.07-3.18).

Conclusions: In this large ECG study, individuals with preexcitation had higher hazards of atrial fibrillation and heart failure. The higher hazard of heart failure seemed to be driven by a right anteroseptal accessory pathway. Among elderly people, we found a statistically significant association between preexcitation and a higher hazard of death.
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http://dx.doi.org/10.1161/CIRCEP.116.004778DOI Listing
June 2017

Electrocardiographic PR Interval Duration and Cardiovascular Risk: Results From the Copenhagen ECG Study.

Can J Cardiol 2017 05 6;33(5):674-681. Epub 2017 Mar 6.

Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen, Denmark; Laboratory for Molecular Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Because of ambiguous reports in the literature, we aimed to investigate the association between PR interval and the risk of all-cause and cardiovascular death, heart failure, and pacemaker implantation, allowing for a nonlinear relationship.

Methods: We included 293,111 individuals, corresponding to one-third of the population in the greater region of Copenhagen. These individuals had a digital electrocardiogram recorded in a general practitioner's core facility from 2001-2011. Data on drug use, comorbidities, and outcomes were collected from Danish registries. We divided the population into 7 groups based on the population PR interval distribution. Cox models were used, with reference to a PR interval between 152 and 161 ms (40th to < 60th percentile).

Results: During follow-up, we identified 34,783 deaths from all causes, 9867 cardiovascular deaths, 9526 cases of incident heart failure, and 1805 pacemaker implantations. A short PR interval (< 125 ms; hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.08-1.41; P = 0.001) as well as a long PR interval (> 200 ms; HR, 1.23; 95% CI, 1.14-1.32; P < 0.001) was associated with an increased risk of cardiovascular death after multivariable adjustment. A long PR interval conferred an increased risk of heart failure (> 200 ms; HR, 1.31; 95% CI, 1.22-1.42; P < 0.001). An increasing PR interval conferred an increased risk of pacemaker implantation, in a dose-response manner, with the highest risk associated with a PR interval > 200 ms (HR, 3.49; 95% CI, 2.96-4.11; P < 0.001).

Conclusions: PR interval was significantly associated with the risk of the adverse outcomes investigated. The nonlinear relationships, in combination with relatively weak associations, could contribute to previously reported conflicting results on the subject.
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http://dx.doi.org/10.1016/j.cjca.2017.02.015DOI Listing
May 2017

Association Between Heart Rate at Rest and Incident Atrial Fibrillation (from the Copenhagen Electrocardiographic Study).

Am J Cardiol 2016 09 14;118(5):708-13. Epub 2016 Jun 14.

Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan.

Heart rate (HR) at rest is a well-known marker of cardiovascular morbidity and mortality. Results on the association between HR and incident atrial fibrillation (AF) have, however, been conflicting. Using digital electrocardiograms from 281,451 primary care patients, we aimed to describe the association between HR at rest and the hazards of incident AF. Secondary end points were death from all causes and pacemaker implantation. Data on drug use, co-morbidity, and outcomes were collected from nationwide administrative health care registries. During a median follow-up time of 8.4 years, 15,666 subjects were observed to develop AF, of which 1,631 were lone AF. A HR at rest from 30 to 51 beats/min was associated with an adjusted hazard ratio of 1.16 (95% CI 1.06 to 1.27) for AF compared with the reference group (66 to 72 beats/min). From 72 beats/min and upward, the hazard ratio of AF increased in a dose-response manner, reaching an adjusted hazard ratio of 1.36 (95% CI 1.26 to 1.46) for HR between 95 and 120 beats/min. Both for low and high HR, the associations were accentuated for the outcome lone AF (adjusted hazard ratios of 1.48, 95% CI 1.19 to 1.84 and 1.84, 95% CI 1.47 to 2.30 for HR between 30 to 51 and 95 to 120 beats/min, respectively). For death from all causes, the hazard increased almost linearly with increasing HR. A HR at rest from 30 to 51 beats/min was associated with an adjusted hazard ratio of 1.80 (95% CI 1.46 to 2.21) for pacemaker implantation. In conclusion, a U-shaped association was found between HR at rest and incident AF, and this association was strongest for the outcome lone AF.
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http://dx.doi.org/10.1016/j.amjcard.2016.06.013DOI Listing
September 2016

Electrocardiographic Tpeak-Tend interval and risk of cardiovascular morbidity and mortality: Results from the Copenhagen ECG study.

Heart Rhythm 2016 Apr 18;13(4):915-24. Epub 2015 Dec 18.

Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen, Denmark; Laboratory for Molecular Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan. Electronic address:

Background: The electrocardiographic Tpeak-Tend interval is considered a novel risk marker of cardiac arrhythmias and cardiovascular death; however, results to date have been conflicting.

Objective: The purpose of this study was to investigate the association between this interval and the risk of all-cause and cardiovascular mortality, atrial fibrillation, and heart failure, allowing for nonlinear relationships.

Methods: From primary care, 138,404 individuals were included and categorized into seven groups based on Tpeak-Tend interval. Cox regression models were used to describe the association between these groups and the risk of the selected outcomes.

Results: Compared with the reference groups (104-115 ms for all-cause mortality and 98-103 ms for all other outcomes), individuals with a Tpeak-Tend interval in lead V5 <5th percentile (58-77 ms) had hazard ratios of 1.29 (95% confidence interval [CI] 1.21-1.38, P <.001) for all-cause mortality, 1.31 (95% CI 1.15-1.50, P <.001) for cardiovascular death, 1.18 (95% CI 1.06-1.32, P = .003) for atrial fibrillation, and 1.52 (95% CI 1.33-1.74, P <.001) for heart failure. Individuals with a Tpeak-Tend interval ≥95th percentile (116-140 ms) had hazard ratios of 1.15 (95% CI 1.08-1.23, P <.001) for all-cause mortality, 1.30 (95% CI 1.15-1.47, P <.001) for cardiovascular death, 1.09 (95% CI 0.99-1.22, P = .088) for atrial fibrillation, and 1.28 (95% CI 1.12-1.46, P <.001) for heart failure. Similar results were obtained for leads II and V2.

Conclusion: We observed U-shaped associations between the Tpeak-Tend interval and risk of all-cause and cardiovascular mortality, atrial fibrillation, and heart failure.
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http://dx.doi.org/10.1016/j.hrthm.2015.12.027DOI Listing
April 2016

P-wave duration and the risk of atrial fibrillation: Results from the Copenhagen ECG Study.

Heart Rhythm 2015 Sep 23;12(9):1887-95. Epub 2015 Apr 23.

Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen, Denmark; Laboratory for Molecular Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Results on the association between P-wave duration and the risk of atrial fibrillation (AF) are conflicting.

Objective: The purpose of this study was to obtain a detailed description of the relationship between P-wave duration and the risk of AF.

Methods: Using computerized analysis of electrocardiograms from a large primary care population, we evaluated the association between P-wave duration and the risk of AF. Secondary end-points were death from cardiovascular causes and putative ischemic stroke. Data on drug use, comorbidity, and outcomes were collected from administrative registries.

Results: A total of 285,933 individuals were included. During median follow-up period of 6.7 years, 9550 developed AF, 9371 died of a cardiovascular cause, and 8980 had a stroke. Compared with the reference group (100-105 ms), individuals with very short (≤89 ms; hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.41-1.81), intermediate (112-119 ms; HR 1.22, 95% CI 1.13-1.31), long (120-129 ms; HR 1.50, 95% CI 1.39-1.62), and very long P-wave duration (≥130 ms; HR 2.06, 95% CI 1.89-2.23) had an increased risk of incident AF. With respect to death from cardiovascular causes, we found an increased risk for very short (≤89 ms; HR 1.20, 95% CI 1.06-1.34), long (120-129 ms; HR 1.11, 95% CI 1.04-1.19), and very long P-wave duration (≥130 ms; HR 1.30, 95% CI 1.21-1.40) compared with the reference group (106-111 ms). Similar but weaker associations were found between P-wave duration and the risk of putative ischemic stroke.

Conclusion: In a large primary care population we found both short and long P-wave duration to be robustly associated with an increased risk of AF.
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http://dx.doi.org/10.1016/j.hrthm.2015.04.026DOI Listing
September 2015

Electrocardiographic precordial ST-segment deviations and the risk of cardiovascular death: results from the Copenhagen ECG Study.

J Am Heart Assoc 2014 May 9;3(3):e000549. Epub 2014 May 9.

Danish National Research Foundation Centre for Cardiac Arrhythmia.

Background: We sought to perform a study assessing the association between electrocardiographic ST-segment deviations and cardiovascular death (CVD), in relation to sex and age (≥ and <65 years), in a large primary care population without overt ischemic heart disease.

Methods And Results: Using computerized analysis of ECGs from 285 194 persons, we evaluated the association between precordial ST-segment deviations and the risk of CVD. All data on medication, comorbidity, and outcomes were retrieved from Danish registries. After a median follow-up period of 5.8 years, there were 6679 cardiovascular deaths. Increasing ST-depression was associated with an increased risk of CVD in almost all of the precordial leads, with the most robust association seen in lead V5 to V6. ST-elevations in lead V2 to V6 were associated with increased risk of CVD in young women, but not in men. However, ST-elevations in V1 increased the risk for both genders and age groups, exemplified by a HR of 1.80 (95% CI [1.19 to 2.74], P=0.005) for men <65 years with ST-elevations ≥ 150 μV versus a nondeviating ST-segment (-50 μV to +50 μV). In contrast, for men <65 years, ST-elevations in lead V2 to V3 conferred a decreased risk of CVD with a HR of 0.77 (95% CI [0.62 to 0.96], P<0.001) for ST-elevations ≥ 150 μV in V2.

Conclusion: We found that ST-depressions were associated with a dose-responsive increased risk of CVD in nearly all the precordial leads. ST-elevations conferred an increased risk of CVD in women and with regard to lead V1 also in men. However, ST-elevations in V2 to V3 were associated with a decreased risk of CVD in young men.
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http://dx.doi.org/10.1161/JAHA.113.000549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309043PMC
May 2014

Left anterior fascicular block and the risk of cardiovascular outcomes.

JAMA Intern Med 2014 Jun;174(6):1001-3

Department of Cardiology, Laboratory of Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark2Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark.

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http://dx.doi.org/10.1001/jamainternmed.2014.578DOI Listing
June 2014

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

Eur Heart J 2014 May 6;35(20):1335-44. Epub 2014 Mar 6.

Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen, Denmark Laboratory for Molecular Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1093/eurheartj/ehu081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028611PMC
May 2014

Risk of atrial fibrillation as a function of the electrocardiographic PR interval: results from the Copenhagen ECG Study.

Heart Rhythm 2013 Sep 19;10(9):1249-56. Epub 2013 Apr 19.

Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Copenhagen, Denmark.

Background: Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF).

Objective: To determine if there was a nonlinear relation between PR interval duration and the risk of AF.

Methods: We included 288,181 individuals, corresponding to one third of the population in the greater region of Copenhagen. These individuals had a digital electrocardiogram (ECG) recorded in a general practitioner's core facility from 2001 to 2010. Data on drug use, comorbidity, and outcomes were collected from Danish registries.

Results: During a median follow-up period of 5.7 years, 11,087 developed AF. Having a PR interval ≥95th percentile (≥196 ms for women, ≥204 ms for men) was associated with an increased risk of AF as evidenced by a multivariable-adjusted hazard ratio (HR) of 1.18 (95% confidence interval [CI] 1.06-1.30, P = .001) for women and 1.30 (1.17-1.44, P < .001) for men compared with the respective reference groups (PR interval between 40th and 60th percentile). Having a short PR interval <5th percentile (≤121 ms for women, ≤129 ms for men) was also associated with an increased risk of AF for women (HR 1.32, 95% CI 1.12-1.56, P = .001), but this was not significant for men (HR 1.09, 95% CI 0.92-1.29, P = .33).

Conclusion: In this large ECG study, we found an increased risk of AF for longer PR intervals for both women and men. With respect to short PR intervals, we also observed an increased risk of AF for women.
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http://dx.doi.org/10.1016/j.hrthm.2013.04.012DOI Listing
September 2013

J-shaped association between QTc interval duration and the risk of atrial fibrillation: results from the Copenhagen ECG study.

J Am Coll Cardiol 2013 Jun 12;61(25):2557-64. Epub 2013 Apr 12.

Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark.

Objectives: The aim of this study was to investigate whether the heart rate-corrected QT (QTc) interval on the electrocardiogram (ECG) is associated with the onset of atrial fibrillation (AF).

Background: Patients with hereditary short-QT or long-QT syndromes, representing the very extremes of the QT interval, both seem to have a high prevalence of AF.

Methods: A total of 281,277 subjects were included, corresponding to one-third of the population of the greater region of Copenhagen. These subjects underwent digital ECG recordings in a general practitioner's core facility from 2001 to 2010. Data on drug use, comorbidities, and outcomes were collected from Danish registries.

Results: After a median follow-up period of 5.7 years, 10,766 subjects had developed AF, of whom 1,467 (14%) developed lone AF. Having a QTc interval lower than the first percentile (≤372 ms) was associated with a multivariate-adjusted hazard ratio of 1.45 (95% confidence interval: 1.14 to 1.84; p = 0.002) of AF, compared with the reference group (411 to 419 ms). From the reference group and upward, the risk of AF increased with QTc interval duration in a dose-response manner, reaching a hazard ratio of 1.44 (95% confidence interval: 1.24 to 1.66, p < 0.001) for those with QTc intervals ≥99th percentile (≥464 ms). The association with respect to longer QTc intervals was stronger for the outcome of lone AF, as evidenced by a hazard ratio of 2.32 (95% confidence interval: 1.52 to 3.54, p < 0.001) for having a QTc interval ≥99th percentile (≥458 ms).

Conclusions: In this large ECG study, a J-shaped association was found between QTc interval duration and risk of AF. This association was strongest with respect to the development of lone AF.
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http://dx.doi.org/10.1016/j.jacc.2013.03.032DOI Listing
June 2013

Tissue Doppler echocardiography improves the diagnosis of coronary artery stenosis in stable angina pectoris.

Eur Heart J Cardiovasc Imaging 2012 Sep 8;13(9):724-9. Epub 2012 Feb 8.

Department of Cardiology, Gentofte University Hospital, Post 4210, 65 Niels Andersens Vej, DK-2900 Hellerup, Copenhagen, Denmark.

Unlabelled: Aim To determine if colour tissue Doppler imaging (TDI) performed at rest in patients with suspected stable angina pectoris (SAP) is able to predict the presence of significant coronary artery disease (CAD).

Methods And Results: This study comprises 296 consecutive patients with clinically suspected SAP, no previous cardiac history, and a normal ejection fraction. All patients were examined by colour TDI, exercise electrocardiogram (ECG), and coronary angiography (CAG). Regional longitudinal systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities were measured by colour TDI at six mitral annular sites and averaged to provide global estimates. Duke score (DS), including ST depression, chest pain, and exercise capacity, was used as the outcome of the exercise ECG. Patients with an area stenosis of ≥70% in at least one epicardial coronary artery were categorized as having a significant CAD (n= 108) and were compared with patients without significant CAD (n= 188). Both e' [odds ratio (OR): 1.5 (1.1-1.9, P < 0.01) per cm/s decrease] and s' [OR: 1.7 (1.1-2.5, P < 0.05) per cm/s decrease] remained independent predictors of CAD after multivariable adjustment for baseline, exercise ECG, and conventional echocardiographic parameters. Area under the receiver operating characteristic curve (AUC) for exercise ECG and TDI in combination was significantly higher than AUC for exercise ECG alone (0.84 vs. 0.79, P < 0.01).

Conclusion: In patients with suspected SAP colour TDI performed at rest is an independent predictor of significant CAD, and colour TDI improves the diagnostic performance of exercise ECG.
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http://dx.doi.org/10.1093/ehjci/jes001DOI Listing
September 2012
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