Electrocardiographic markers in patients with type 2 diabetes and the role of diabetes duration.

BACKGROUND: The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. METHODS: In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. RESULTS: We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. CONCLUSIONS: Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration.

Left Atrial Strain Predicts Subclinical Atrial Fibrillation Detected by Long-term Continuous Monitoring in Elderly High-Risk Individuals.

BACKGROUND: Left atrial (LA) speckle tracking provides detailed information on atrial function. Its utility for predicting subclinical atrial fibrillation (SCAF) is unclear. Therefore, we sought to investigate whether LA strain measures could predict SCAF detected by long-term continuous rhythm monitoring. METHODS: This was an echocardiographic substudy of the LOOP study, where elderly at risk of stroke were randomized to receive a loop recorder (Reveal LINQ) or control. Participants who received a loop recorder were included in this analysis. Echocardiography included LA reservoir, conduit, and contraction strain. Participants were followed with continuous rhythm monitoring for SCAF (≥6 minutes). Cox proportional hazards regression was applied to adjust for atrial fibrillation risk factors. RESULTS: In total, 956 participants were eligible for analysis. Median continuous rhythm monitoring was 35 months (IQR, 20-40 months), during which 278 (29%) were diagnosed with SCAF. The mean age was 74 years, 56% were male, median CHA2DS2-VASc-score was 4. LA reservoir strain was an independent predictor of SCAF after multivariable adjustments (HR, 1.04 [1.02-1.05], per 1% decrease) and so was contraction strain. The findings were unchanged in competing risk analyses and in participants with normal LA size and diastolic function. Participants with low reservoir strain (<33%) had a significantly higher risk of SCAF compared with those with high reservoir strain (incidence rate, 14.5 [12.4-16.9] versus 9.8 [8.2-11.8] events/100 person-years). The same was noted for low versus high contraction strain. CONCLUSIONS: LA reservoir and contraction strain are independent predictors of SCAF in elderly at risk of stroke. This also applies to individuals with normal LA size and diastolic function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

The ABC-Stroke Risk Score and Effects of Atrial Fibrillation Screening on Stroke Prevention: Results From the Randomized LOOP Study.

BACKGROUND: The ABC-stroke score is a risk scheme for prediction of stroke or systemic embolism (SE) in atrial fibrillation (AF). This study sought to examine whether the score could be useful in predicting stroke in AF-naïve individuals and risk stratifying for AF screening. METHODS AND RESULTS: The LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals) study randomized 6004 AF-naïve individuals aged 70 to 90 years with stroke risk factors to either screening with an implantable loop recorder and anticoagulation upon detection of new-onset AF episodes ≥6 minutes, or usual care. A total of 5781 participants had available ABC-stroke score at baseline and were included in this secondary analysis: 4170 (72.1%) with an estimated stroke/SE risk ≤1%/year versus 1611 (27.9%) with an estimated stroke/SE risk >1%/year. Having an annual ABC-stroke risk >1% was associated with stroke/SE, stroke/SE/cardiovascular death, and all-cause death (hazard ratio, 1.82 [95% CI, 1.44-2.21], 2.17 [95% CI, 1.80-2.62], and 2.19 [95% CI, 1.87-2.56], respectively). For screening with implantable loop recorder versus usual care, no significant reduction in these study outcomes was obtained in any ABC-stroke risk groups (P>0.0500 for all), with no signal toward interaction (Pinteraction>0.2500 for all). Similar findings were yielded when assessing the ABC-stroke score as a continuous variable. CONCLUSIONS: In an elderly, AF-naïve population with additional stroke risk factors, a higher ABC-stroke score could identify individuals with increased stroke risk. However, this risk score may not be useful in pinpointing those more likely to benefit from AF screening and subsequent preventive treatment. These findings should be considered as hypothesis generating and warrant further study. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT02036450.

The Danish Nationwide Electrocardiogram (ECG) Cohort.

The electrocardiogram (ECG) is a non-invasive diagnostic tool holding significant clinical importance in the diagnosis and risk stratification of cardiac disease. However, access to large-scale, population-based digital ECG data for research purposes remains limited and challenging. Consequently, we established the Danish Nationwide ECG Cohort to provide data from standard 12-lead digital ECGs in both pre- and in-hospital settings, which can be linked to comprehensive Danish nationwide administrative registers on health and social data with long-term follow-up. The Danish Nationwide ECG Cohort is an open real-world cohort including all patients with at least one digital pre- or in-hospital ECG in Denmark from January 01, 2000, to December 31, 2021. The cohort includes data on standardized and uniform ECG diagnostic statements and ECG measurements including global parameters as well as lead-specific measures of waveform amplitudes, durations, and intervals. Currently, the cohort comprises 2,485,987 unique patients with a median age at the first ECG of 57 years (25th-75th percentiles, 40-71 years; males, 48%), resulting in a total of 11,952,430 ECGs. In conclusion, the Danish Nationwide ECG Cohort represents a novel and extensive population-based digital ECG dataset for cardiovascular research, encompassing both pre- and in-hospital settings. The cohort contains ECG diagnostic statements and ECG measurements that can be linked to various nationwide health and social registers without loss to follow-up.

Epicardial adipose tissue and subclinical incident atrial fibrillation as detected by continuous monitoring: a cardiac magnetic resonance imaging study.

Epicardial adipose tissue (EAT) has endocrine and paracrine functions and has been associated with metabolic and cardiovascular disease. This study aimed to investigate the association between EAT, determined by cardiac magnetic resonance imaging (CMR), and incident atrial fibrillation (AF) following long-term continuous heart rhythm monitoring by implantable loop recorder (ILR). This study is a sub-study of the LOOP study. In total, 203 participants without a history of AF received an ILR and underwent advanced CMR. All participants were at least 70 years of age at inclusion and had at least one of the following conditions: hypertension, diabetes, previous stroke, or heart failure. Volumetric measurements of atrial- and ventricular EAT were derived from CMR and the time to incident AF was subsequently determined. A total of 78 participants (38%) were diagnosed with subclinical AF during a median of 40 (37-42) months of continuous monitoring. In multivariable Cox regression analyses adjusted for age, sex, and various comorbidities, we found EAT indexed to body surface area to be independently associated with the time to AF with hazard ratios (95% confidence intervals) up to 2.93 (1.36-6.34); p = 0.01 when analyzing the risk of new-onset AF episodes lasting ≥ 24 h. Atrial EAT assessed by volumetric measurements on CMR images was significantly associated with the incident AF episodes as detected by ILR.

Anticoagulation-Associated Bleeding in Patients Screened for Atrial Fibrillation versus Usual Care-A Post Hoc Analysis from the LOOP Study.

Background Atrial fibrillation (AF) prevalence is rising; however, data on the bleeding risks associated with the detection of subclinical AF are needed. Objective Our objective was to determine the bleeding increment associated with implantable loop recorder (ILR) screening for subclinical AF and subsequent anticoagulation initiation compared with usual care. Methods This post hoc study utilized LOOP trial data from 6,004 elderly patients with stroke risks randomized to either ILR ( n = 1,503) or usual care ( n = 4,503). The mean follow-up time was 64.5 months, and none were lost to follow-up. The primary exposure was the initiation of oral anticoagulation, and the main outcome was the risk of major bleeding events following initiation of oral anticoagulants (OACs), determined by time-dependent cox regression. Second, we investigated antithrombotic prescription patterns and major bleeding events after antiplatelet treatment and in subgroups. Results OAC was initiated in 1,019 participants with a mean age (years) of 78.8 (± 4.67) in control versus 77.0 (± 4.84) in ILR, p < 0.0001. Altogether did 202 participants end or pause OAC treatment. Among AF patients (n = 910) had 40 (28%) completely ended OAC and 105 (72%) temporarily paused OAC during follow-up. Major bleeding events totaled 221 (3.7%). Forty-seven major bleeding events followed an OAC initiation in 1,019 participants (4.6%); 26 versus 21 events in the control and ILR groups, respectively. The hazard ratio (HR) for major bleeding after OAC initiation compared with before initiation was 2.08 (1.50-2.90) p < 0.0001 overall, 2.81 (1.82-4.34) p < 0.0001 for control and 1.32 (0.78-2.23) p = 0.31 for the ILR group ( p = 0.07 for interaction). Antiplatelet treatment resulted in an overall adjusted HR of 1.3 (0.96-1.75) p = 0.09. For OAC users aged ≥75 years in the ILR group, the rate of major bleeding was 1.73 (0.92-2.96) compared with 0.84 (0.36-1.66) for an age <75 years, and the rate of the corresponding control subgroup aged ≥75 years was 2.20 (1.23-3.63) compared with 1.64 (0.82-2.93) for an age <75 years. Conclusion The individual risk of major bleeding increased twofold after initiation of oral anticoagulation for all patients in this study. However, the patients screened for subclinical AF did not have a higher bleeding risk after initiation of anticoagulation compared with those in usual care. Trial Registration: The LOOP study is registered at ClinicalTrials.gov, identifier: NCT020364 50.

Electrocardiographic Morphology-Voltage-P-Wave-Duration (MVP) Score to Select Patients for Continuous Atrial Fibrillation Screening to Prevent Stroke.

Morphology-voltage-P-wave-duration (MVP) score combining P-wave duration (PWD), P-wave voltage in lead I (PWVI), and interatrial block (IAB) has been demonstrated to predict atrial fibrillation (AF). Therefore, this study aimed to examine MVP score and its P-wave components as potential predictors of AF screening effects on stroke prevention. This was a secondary analysis of the LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) which randomized older persons (aged 70 to 90 years) with additional stroke risk factors to either continuous monitoring with implantable loop recorder and anticoagulation upon detection of AF episodes ≥6 minutes (the intervention group), or usual care. A total of 5,759 participants were included in the present analysis, where PWD, PWVI, and IAB were determined through a computerized analysis of 12-lead electrocardiogram and further employed to calculate baseline MVP score (0 to 6) for each participant. In total, 305 (5.3%) had stroke or systemic embolism during follow-up, with a higher risk in the group with MVP score 5 to 6 than those having score 0 to 2 (hazard ratio (HR) 1.54 [95% confidence interval (CI) 1.01 to 2.35]). This risk increase was mainly upheld by participants with IAB (HR 1.62 [95% CI 1.11 to 2.36] for IAB vs no IAB) and with longer PWD (HR 1.37 [95% CI 1.07 to 1.75] for >110 vs ≤110 ms). Compared with usual care, implantable loop recorder screening did not significantly reduce the risk of stroke or systemic embolism in any MVP risk categories (HR 0.80 [95% CI 0.60 to 1.08] for MVP score 0 to 2, 0.54 [95% CI 0.16 to 1.85] for MVP score 3 to 4, and 0.89 [95% CI 0.35 to 2.25] for MVP score 5 to 6; pinteraction = 0.78). In conclusion, a higher MVP score was associated with an increased stroke risk, but it did not demonstrate an association with effects of AF screening on stroke prevention. These findings should be considered hypothesis-generating and warrant further study.

The role of contractile dyssynchrony in pacing-induced cardiomyopathy: detailed assessment using index of contractile asymmetry.

AIMS: The pathophysiological effects of chronic right ventricular pacing and the role of right ventricular lead position are not well understood. Therefore, we investigated the association between left ventricular contractile dyssynchrony and pacing-induced cardiomyopathy (PICM) in patients with chronic right ventricular pacing. Furthermore, we assessed the association between right ventricular lead location and left ventricular contractile dyssynchrony. METHODS: This was a retrospective study using data from 153 pacemaker patients with normal (≥ 50%) pre-implant left ventricular ejection fraction (LVEF). Baseline and follow-up echocardiograms were analyzed, and PICM was defined as LVEF < 50% with ≥ 10% decrease in LVEF after pacemaker implantation. Relative index of contractile asymmetry (rICA), a novel strain rate-based method, was calculated to quantify left ventricular contractile dyssynchrony between opposing walls in the three apical views. Right ventricular lead position was categorized into anterior septum, posterior septum, free wall, and apex based on contrast-enhanced cardiac computed tomography. RESULTS: Forty-seven (31%) developed PICM. Overall contractile dyssynchrony, measured by mean rICA, was higher in the PICM group compared with the non-PICM group (1.19 ± 0.21 vs. 1.03 ± 0.19, p < 0.001). Left ventricular anterior-inferior dyssynchrony, assessed in the apical two-chamber view, was independently associated with PICM (p < 0.001). Thirty-seven (24%) leads were implanted anterior septal, 11 (7.2%) posterior septal, 74 (48.4%) apical, and 31 (20.3%) free wall. Left ventricular anterior-inferior dyssynchrony was significantly different between the four pacing lead locations (p < 0.01) with the highest rICA observed in the posterior septal group (1.30 ± 0.37). CONCLUSIONS: PICM is significantly associated increased contractile dyssynchrony assessed by rICA. This study suggests that especially left ventricular dyssynchrony in the anterior-inferior direction is associated with PICM, and pacing the right ventricular posterior septum resulted in the highest degree of anterior-inferior dyssynchrony. Quantification of left ventricular dyssynchrony by rICA provides important insights to the potential pathophysiology of PICM and the impact of right ventricular lead position.

PTB-XL+, a comprehensive electrocardiographic feature dataset.

Machine learning (ML) methods for the analysis of electrocardiography (ECG) data are gaining importance, substantially supported by the release of large public datasets. However, these current datasets miss important derived descriptors such as ECG features that have been devised in the past hundred years and still form the basis of most automatic ECG analysis algorithms and are critical for cardiologists' decision processes. ECG features are available from sophisticated commercial software but are not accessible to the general public. To alleviate this issue, we add ECG features from two leading commercial algorithms and an open-source implementation supplemented by a set of automatic diagnostic statements from a commercial ECG analysis software in preprocessed format. This allows the comparison of ML models trained on clinically versus automatically generated label sets. We provide an extensive technical validation of features and diagnostic statements for ML applications. We believe this release crucially enhances the usability of the PTB-XL dataset as a reference dataset for ML methods in the context of ECG data.

Does targeted positioning of the left ventricular pacing lead towards the latest local electrical activation in cardiac resynchronization therapy reduce the incidence of death or hospitalization for heart failure?

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement. METHODS: The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024. CONCLUSIONS: The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. GOV IDENTIFIER: NCT03280862.

Ventricular rate in atrial fibrillation and the risk of heart failure and death.

AIMS: While clinical trials have suggested that a high ventricular rate is associated with increased risk of heart failure (HF) and mortality, all-comers studies are warranted. OBJECTIVE: To assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate. METHODS AND RESULTS: ECGs recorded at the Copenhagen General Practitioners Laboratory (2001-15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [<60, 60-79, 80-99, and 100-110, > 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70-85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71-101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100-110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10-1.95) and 2.41 (CI: 1.94-3.00) respectively for new-onset HF, compared with 60-79 bpm. Similarly, patients with AF ventricular rates 100-110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13-1.82) and 1.34 (CI: 1.08-1.65) respectively for all-cause mortality, compared with 60-79 bpm. CONCLUSIONS: Ventricular rates ≥100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality.

Effects of Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: A Secondary Analysis of the Randomized LOOP Study.

BACKGROUND: Research suggests NT-proBNP (N-terminal pro-B-type natriuretic peptide) to be a strong predictor of incident atrial fibrillation (AF) and stroke. However, its utility in AF screening remains unknown. The aim of this study was to investigate NT-proBNP as a potential marker for screening efficacy with respect to AF yield and stroke prevention. METHODS: In the LOOP Study (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals), 6004 AF-naïve individuals at least 70 years old and with additional stroke risk factors were randomized 1:3 to either screening with an implantable loop recorder (ILR) and initiation of anticoagulation upon detection of AF episodes lasting ≥6 minutes or usual care (control). This post hoc analysis included study participants with available NT-proBNP measurement at baseline. RESULTS: A total of 5819 participants (96.9% of the trial population) were included. The mean age was 74.7 years (SD, 4.1 years) and 47.5% were female. The median NT-proBNP level was 15 pmol/L (interquartile range, 9-28 pmol/L) corresponding to 125 pg/mL (interquartile range, 76-233 pg/mL). NT-proBNP above median was associated with an increased risk of AF diagnosis both in the ILR group (hazard ratio, 1.84 [95% CI, 1.51-2.25]) and the control group (hazard ratio, 2.79 [95% CI, 2.30-3.40]). Participants with NT-proBNP above the median were also at higher risk of clinical events compared with those having lower levels (hazard ratio, 1.21 [95% CI, 0.96-1.54] for stroke or systemic embolism [SE], 1.60 [95% CI, 1.32-1.95] for stroke/SE/cardiovascular death, and 1.91 [95% CI, 1.61-2.26] for all-cause death). Compared with usual care, ILR screening was associated with significant reductions in stroke/SE and stroke/SE/cardiovascular death among participants with NT-proBNP above median (hazard ratio, 0.60 [95% CI, 0.40-0.90] and 0.70 [95% CI, 0.53-0.94], respectively) but not among those with lower levels (Pinteraction=0.029 for stroke/SE and 0.045 for stroke/SE/cardiovascular death). No risk reduction in all-cause death was observed in either NT-proBNP subgroup for ILR versus control (Pinteraction=0.68). Analyzing NT-proBNP as a continuous variable yielded similar findings. CONCLUSIONS: In an older population with additional stroke risk factors, ILR screening for AF was associated with a significant reduction in stroke risk among individuals with higher NT-proBNP levels but not among those with lower levels. These findings should be considered hypothesis generating and warrant further study before clinical implementation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02036450.

Electrocardiographic markers of subclinical atrial fibrillation detected by implantable loop recorder: insights from the LOOP Study.

AIMS: Insights into subclinical atrial fibrillation (AF) development are warranted to inform the strategies of screening and subsequent clinical management upon AF detection. Hence, this study sought to characterize the onset and progression of subclinical AF with respect to 12-lead electrocardiogram (ECG) parameters. METHODS AND RESULTS: We included AF-naïve individuals aged 70-90 years with additional stroke risk factors who underwent implantable loop recorder (ILR) monitoring in the LOOP Study. Using data from daily ILR recordings and the computerized analysis of baseline ECG, we studied empirically selected ECG parameters for AF detection (≥6 min), cumulative AF burden, long-lasting AF (≥24 h), and AF progression. Of 1370 individuals included, 419 (30.6%) developed AF during follow-up, with a mean cumulative AF burden of 1.5% [95% CI: 1.2-1.8]. Several P-wave-related and ventricular ECG parameters were associated with new-onset AF and with cumulative AF burden in AF patients. P-wave duration (PWD), P-wave terminal force in Lead V1, and interatrial block (IAB) further demonstrated significant associations with long-lasting AF. Among AF patients, we observed an overall reduction in cumulative AF burden over time (IRR 0.70 [95% CI: 0.51-0.96]), whereas IAB was related to an increased risk of progression to AF ≥24 h (HR 1.86 [95% CI: 1.02-3.39]). Further spline analysis also revealed longer PWD to be associated with this progression in AF duration. CONCLUSION: We identified several ECG parameters associated with new-onset subclinical AF detected by ILR. Especially PWD and IAB were robustly related to the onset and the burden of AF as well as progression over time.

Novel non-invasive ECG imaging method based on the 12-lead ECG for reconstruction of ventricular activation: A proof-of-concept study.

Aim: Current non-invasive electrocardiographic imaging (ECGi) methods are often based on complex body surface potential mapping, limiting the clinical applicability. The aim of this pilot study was to evaluate the ability of a novel non-invasive ECGi method, based on the standard 12-lead ECG, to localize initial site of ventricular activation in right ventricular (RV) paced patients. Validation of the method was performed by comparing the ECGi reconstructed earliest site of activation against the true RV pacing site determined from cardiac computed tomography (CT). Methods: This was a retrospective study using data from 34 patients, previously implanted with a dual chamber pacemaker due to advanced atrioventricular block. True RV lead position was determined from analysis of a post-implant cardiac CT scan. The ECGi method was based on an inverse-ECG algorithm applying electrophysiological rules. The algorithm integrated information from an RV paced 12-lead ECG together with a CT-derived patient-specific heart-thorax geometric model to reconstruct a 3D electrical ventricular activation map. Results: The mean geodesic localization error (LE) between the ECGi reconstructed initial site of activation and the RV lead insertion site determined from CT was 13.9 ± 5.6 mm. The mean RV endocardial surface area was 146.0 ± 30.0 cm2 and the mean circular LE area was 7.0 ± 5.2 cm2 resulting in a relative LE of 5.0 ± 4.0%. Conclusion: We demonstrated a novel non-invasive ECGi method, based on the 12-lead ECG, that accurately localized the RV pacing site in relation to the ventricular anatomy.

Prevalence and Prognostic Significance of Bradyarrhythmias in Patients Screened for Atrial Fibrillation vs Usual Care: Post Hoc Analysis of the LOOP Randomized Clinical Trial.

Importance: There is increasing interest in heart rhythm monitoring and technologies to detect subclinical atrial fibrillation (AF), which may lead to incidental diagnosis of bradyarrhythmias. Objective: To assess bradyarrhythmia prevalence and prognostic significance in persons screened for AF using implantable loop recorder (ILR) compared with unscreened persons. Design, Setting, and Participants: This was a post hoc analysis of the Implantable Loop Recorder Detection of Atrial Fibrillation to Prevent Stroke (LOOP) randomized clinical trial, which took place in 4 sites in Denmark. Participants were 70 years or older without known AF but diagnosed with at least 1 of the following: hypertension, diabetes, heart failure, or prior stroke. Participants were recruited by letter invitation between January 31, 2014, and May 17, 2016. The median (IQR) follow-up period was 65 (59-70) months. Analysis took place between February and June 2022. Interventions: ILR screening for AF with treatment of any bradyarrhythmia left to the discretion of the treating physician (ILR group) vs usual care (control group). Main Outcomes and Measures: Adjudicated bradyarrhythmia episodes, pacemaker implantation, syncope, and sudden cardiovascular death. Results: A total of 6004 participants were randomized (mean [SD] age, 75 [4.1] years; 2837 [47.3%] female; 5444 [90.7%] with hypertension; 1224 [20.4%] with prior syncope), 4503 to control and 1501 to ILR. Bradyarrhythmia was diagnosed in 172 participants (3.8%) in the control group vs 312 participants (20.8%) in the ILR group (hazard ratio [HR], 6.21 [95% CI, 5.15-7.48]; P < .001), and these were asymptomatic in 41 participants (23.8%) vs 249 participants (79.8%), respectively. The most common bradyarrhythmia was sinus node dysfunction followed by high-grade atrioventricular block. Risk factors for bradyarrhythmia included higher age, male sex, and prior syncope. A pacemaker was implanted in 132 participants (2.9%) vs 67 (4.5%) (HR, 1.53 [95% CI, 1.14-2.06]; P < .001), syncope occurred in 120 (2.7%) vs 33 (2.2%) (HR, 0.83 [95% CI, 0.56-1.22]; P = .34), and sudden cardiovascular death occurred in 49 (1.1%) vs 18 (1.2%) (HR, 1.11 [95% CI, 0.64-1.90]; P = .71) in the control and ILR groups, respectively. Bradyarrhythmias were associated with subsequent syncope, cardiovascular death, and all-cause death, with no interaction between bradyarrhythmia and randomization group. Conclusions and Relevance: More than 1 in 5 persons older than 70 years with cardiovascular risk factors can be diagnosed with bradyarrhythmias when long-term continous monitoring for AF is applied. In this study, ILR screening led to a 6-fold increase in bradyarrhythmia diagnoses and a significant increase in pacemaker implantations compared with usual care but no change in the risk of syncope or sudden death.

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.

Screening for atrial fibrillation to prevent stroke in elderly individuals with or without preexisting cardiovascular disease: A post hoc analysis of the randomized LOOP Study.

BACKGROUND: An evidence-based approach for risk stratification of subclinical atrial fibrillation (AF) and hereby AF screening is lacking. This study aimed to investigate whether established cardiovascular diseases (CVD) could help to identify the population more likely to benefit from AF screening. METHODS: The LOOP Study randomized AF-naïve individuals aged ≥70 years and with additional stroke risk factors to either screening with implantable loop recorder (ILR) and subsequent anticoagulation upon detection of new-onset AF episodes ≥6 min, or usual care. In this sub-study, all participants were divided into two risk groups according to the presence/absence of CVD (defined as ischemic heart disease, heart failure, previous stroke, valvular heart disease, or peripheral artery disease). RESULTS: A total of 1997 (33.3%) had CVD at baseline and experienced higher incidences of stroke or systemic arterial embolism (SAE), ischemic stroke, stroke/SAE/cardiovascular death, and all-cause death (adjusted HR 1.34 [1.06-1.69], 1.31 [1.02-1.69], 1.49 [1.23-1.79], and 1.59 [1.36-1.85], respectively) than those without. For ILR screening versus usual care, there was no decrease in stroke/SAE, ischemic stroke, or stroke/SAE/cardiovascular death among participants with CVD (adjusted p-values >0.05), whereas significant reductions in these outcomes were obtained by screening among those without CVD (adjusted HR 0.64 [0.44-0.93], 0.54 [0.35-0.82], 0.64 [0.46-0.87], respectively); adjusted p-values for interaction ≤0.05. CONCLUSIONS: In an elderly, at-risk population, ILR screening did not prevent stroke significantly in individuals with CVD, whereas screening was associated with approximately 40% stroke risk reduction among those without CVD. However, these findings should be considered as hypothesis-generating and warrant further study.

Electrocardiographic P terminal force in lead V1, its components, and the association with stroke and atrial fibrillation or flutter.

BACKGROUND: The electrocardiographic (ECG) marker P terminal force V1 (PTFV1) is generally perceived as a marker of left atrial pathology and has been associated with atrial fibrillation or flutter (AF). OBJECTIVE: The purpose of this study was to determine the association between PTFV1 components (duration and amplitude) and incident AF and stroke/transient ischemic attack (TIA). METHODS: The study included patients with an ECG recorded at the Copenhagen General Practitioners Laboratory in 2001 to 2011. PTFV1 ≥4 mV·ms was considered abnormal. Patients with abnormal PTFV1 were stratified into tertiles based on duration (PTDV1) and amplitude (PTAV1) values. Cox regressions adjusted for age, sex, and relevant comorbidities were used to investigate associations between abnormal PTFV1 components and AF and stroke/TIA. RESULTS: Of 267,636 patients, 5803 had AF and 18,176 had stroke/TIA (follow-up 6.5 years). Abnormal PTFV1 was present in 44,549 subjects (16.7%) and was associated with an increased risk of AF and stroke/TIA. Among patients with abnormal PTFV1, the highest tertile of PTDV1 (78-97 ms) was associated with the highest risk of AF (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.23-1.52) and highest risk of stroke/TIA (HR 1.13; 95% CI 1.05 -1.20). For PTAV1, the highest tertile (78-126 µV) conferred the highest risk of AF and stroke/TIA (HR 1.20; 95% CI 1.09-1.32; and HR 1.21; 95% CI 1.14-1.25, respectively). CONCLUSION: Abnormal PTFV1 was associated with an increased risk of AF and stroke/TIA. Increasing PTDV1 showed a dose-response relationship with the development of AF and stroke/TIA, whereas the association between PTAV1 and AF was less apparent.

Risk of Pacing-Induced Cardiomyopathy in Patients with High-Degree Atrioventricular Block-Impact of Right Ventricular Lead Position Confirmed by Computed Tomography.

Prospective studies applying fluoroscopy for assessment of right ventricular (RV) lead position have failed to show clear benefits from RV septal pacing. We investigated the impact of different RV lead positions verified by computed tomography (CT) on the risk of pacing-induced cardiomyopathy (PICM). We retrospectively included 153 patients who underwent routine fluoroscopy-guided pacemaker implantation between March 2012 and May 2020. All patients had normal pre-implant left ventricular ejection fraction (LVEF). Patients attended a follow-up visit including contrast-enhanced cardiac CT and transthoracic echocardiography. Patients were classified as septal or non-septal based on CT analysis. The primary endpoint was PICM (LVEF < 50% with ≥10% decrease after implantation). Based on CT, 48 (31.4%) leads were septal and 105 (68.6%) were non-septal. Over a median follow-up of 3.1 years, 16 patients (33.3%) in the septal group developed PICM compared to 31 (29.5%) in the non-septal group (p = 0.6). Overall, 13.1% deteriorated to LVEF ≤ 40%, 5.9% were upgraded to cardiac resynchronization therapy device, and 14.4% developed new-onset atrial fibrillation, with no significant differences between the groups. This study demonstrated a high risk of PICM despite normal pre-implant left ventricular systolic function with no significant difference between CT-verified RV septal or non-septal lead position.

Non-invasive estimation of QLV from the standard 12-lead ECG in patients with left bundle branch block.

Background: Cardiac resynchronization therapy (CRT) is a treatment for patients with heart failure and electrical dyssynchrony, i.e., left bundle branch block (LBBB) ECG pattern. CRT resynchronizes ventricular contraction with a right ventricle (RV) and a left ventricle (LV) pacemaker lead. Positioning the LV lead in the latest electrically activated region (measured from Q wave onset in the ECG to LV sensing by the left pacemaker electrode [QLV]) is associated with favorable outcome. However, optimal LV lead placement is limited by coronary venous anatomy and the inability to measure QLV non-invasively before implantation. We propose a novel non-invasive method for estimating QLV in sinus-rhythm from the standard 12-lead ECG. Methods: We obtained 12-lead ECG, LV electrograms and LV lead position in a standard LV 17-segment model from procedural recordings from 135 standard CRT recipients. QLV duration was measured post-operatively. Using a generic heart geometry and corresponding forward model for ECG computation, the electrical activation pattern of the heart was fitted to best match the 12-lead ECG in an iterative optimization procedure. This procedure initialized six activation sites associated with the His-Purkinje system. The initial timing of each site was based on the directions of the vectorcardiogram (VCG). Timing and position of the sites were then changed iteratively to improve the match between simulated and measured ECG. Noninvasive estimation of QLV was done by calculating the time difference between Q-onset on the computed ECG and the activation time corresponding to centroidal epicardial activation time of the segment where the LV electrode is positioned. The estimated QLV was compared to the measured QLV. Further, the distance between the actual LV position and the estimated LV position was computed from the generic ventricular model. Results: On average there was no difference between QLV measured from procedural recordings and non-invasive estimation of QLV ( Δ Q L V = - 3.0 ± 22.5 m s , p = 0.12 ). Median distance between actual LV pacing site and the estimated pacing site was 18.6 mm (IQR 17.3 mm). Conclusion: Using the standard 12-lead ECG and a generic heart model it is possible to accurately estimate QLV. This method may potentially be used to support patient selection, optimize implant procedures, and to simulate optimal stimulation parameters prior to pacemaker implantation.