Genetic Susceptibility to Hidradenitis Suppurativa and Predisposition to Cardiometabolic Disease.

Importance: Hidradenitis suppurativa (HS) is associated with an increased prevalence of cardiovascular diseases compared with the general population. Any association between polygenic risk for HS, risk of incident cardiometabolic outcomes, and the plasma proteome is unclear. Objective: To investigate the genetic correlation between HS and cardiometabolic disease. Design, Setting, and Participants: This cohort study used a polygenic risk score (PRS) for HS to examine the risks of coronary artery disease (CAD) and diabetes and identify changes in the plasma proteome in individuals of European ancestry from the UK Biobank. Participants were enrolled from January 1, 2006, to December 31, 2010. End of follow-up was January 1, 2023. Correlations were assessed between HS susceptibility and cardiometabolic traits using linkage disequilibrium score regression. Odds ratios were assessed in logistic regressions. The risk of incident CAD and diabetes was estimated in cause-specific survival models designed as time-to-event analyses. Exposure: The PRS for HS. Main Outcomes and Measures: Main outcomes were CAD and diabetes diagnosis measured by logistic regressions and incident disease measured by Cox proportional hazards regression models adjusted for sex, age, body mass index, and smoking status. Results: The study included 391 481 individuals (median [IQR] age, 58 [51-64] years; 209 235 [53%] female). Genetic variants for HS correlated significantly with variants associated with CAD, diabetes, and plasma levels of high-density lipoprotein cholesterol, triglycerides, and C-reactive protein. Compared with the low-risk group, a high PRS for HS (≥75th percentile) conferred odds ratios of 1.09 (95% CI, 1.06-1.12; P < .001) for CAD and 1.13 (95% CI, 1.10-1.17; P < .001) for diabetes. Estimates remained consistent when examining only incident CAD and diabetes. The PRS for HS was significantly associated with altered expression of 58 plasma proteins. Integrating this proteomic profile and the PRS for HS in a machine learning model improved prediction of CAD and diabetes compared with a reference model based on sex, age, and body mass index. Conclusions and Relevance: These findings suggest that a high genetic risk of HS is associated with increased risk of subsequent CAD and diabetes and altered composition of the plasma proteome. Additional investigation into the identified proteins and their potential roles as drug targets is warranted.

Deep behavioural representation learning reveals risk profiles for malignant ventricular arrhythmias.

We aimed to identify and characterise behavioural profiles in patients at high risk of SCD, by using deep representation learning of day-to-day behavioural recordings. We present a pipeline that employed unsupervised clustering on low-dimensional representations of behavioural time-series data learned by a convolutional residual variational neural network (ResNet-VAE). Data from the prospective, observational SafeHeart study conducted at two large tertiary university centers in the Netherlands and Denmark were used. Patients received an implantable cardioverter-defibrillator (ICD) between May 2021 and September 2022 and wore wearable devices using accelerometer technology during 180 consecutive days. A total of 272 patients (mean age of 63.1 ± 10.2 years, 81% male) were eligible with a total sampling of 37,478 days of behavioural data (138 ± 47 days per patient). Deep representation learning identified five distinct behavioural profiles: Cluster A (n = 46) had very low physical activity levels and a disturbed sleep pattern. Cluster B (n = 70) had high activity levels, mainly at light-to-moderate intensity. Cluster C (n = 63) exhibited a high-intensity activity profile. Cluster D (n = 51) showed above-average sleep efficiency. Cluster E (n = 42) had frequent waking episodes and poor sleep. Annual risks of malignant ventricular arrhythmias ranged from 30.4% in Cluster A to 9.8% and 9.5% for Clusters D-E, respectively. Compared to low-risk profiles (D-E), Cluster A demonstrated a three-to-four fold increased risk of malignant ventricular arrhythmias adjusted for clinical covariates (adjusted HR 3.63, 95% CI 1.54-8.53, p < 0.001). These behavioural profiles may guide more personalised approaches to ventricular arrhythmia and SCD prevention.

Relationship between activity and sleep, as measured through a wearable accelerometer, and appropriate cardioverter defibrillator interventions: a prospective SafeHeart substudy.

AIMS: Physical activity has shown association with ventricular arrhythmia, however, the role of specific behavioral patterns over a 24 h cycle remains unknown. Therefore, we aimed to explore associations between physical behavior and appropriate implantable cardioverter defibrillator (ICD) therapy. METHODS AND RESULTS: We included patients with an ICD at two European sites, who wore wrist-based accelerometers capturing 24 h movement and sleep behaviours for 28 days. Behavioural measures included activity volume, duration and intensity, sleep duration, and efficiency. Participants were followed for 12 months for the outcome of appropriate ICD therapy. Cox proportional hazard models with restricted cubic splines were used for the analysis. Lastly, the predictive capacity was tested. A total of 253 ICD patients were included (mean age 63.5 (±10.2), 48 (19.0%) female). During follow-up, 40 participants (15.8%) received appropriate ICD therapy; 32 anti-tachycardia pacing (ATP) only (12.6%), 5 shock only (2.0%), and 3 combined ATP and shock (1.2%). In the adjusted model, high inactive duration (HR 1.40 (95% 1.10-1.78)), peak walking cadence (HR 1.07 (95% 1.03-1.12)), and total sleep duration (HR 1.50 (1.02-2.22)) were associated with the outcome. The dose-response relationship was U-shaped for inactive duration with a cut-off at 16 h, and linear for peak cadence and sleep. The prediction model reached an area under the receiver operating characteristic curve of 0.70 ± 0.03, with highest accuracy in the first months. CONCLUSION: Wearable-derived 24 h movement and sleep behaviours collected over 28 days were associated with later appropriate ICD therapy risk. Testing of the predictive value of digital biomarkers for enhanced risk stratification of ventricular arrhythmia warrants larger prospective studies. CLINICAL TRIAL REGISTRATION: National Trial Registration (NL9218, http://onderzoekmetmensen.nl/).

Genome-Wide Association Study of Accessory Atrioventricular Pathways.

Importance: Understanding of the genetics of accessory atrioventricular pathways (APs) and affiliated arrhythmias is limited. Objective: To investigate the genetics of APs and affiliated arrhythmias. Design, Setting, and Participants: This was a genome-wide association study (GWAS) of APs, defined by International Classification of Diseases (ICD) codes and/or confirmed by electrophysiology (EP) study. Genome-wide significant AP variants were tested for association with AP-affiliated arrhythmias: paroxysmal supraventricular tachycardia (PSVT), atrial fibrillation (AF), ventricular tachycardia, and cardiac arrest. AP variants were also tested in data on other heart diseases and measures of cardiac physiology. Individuals with APs and control individuals from Iceland (deCODE Genetics), Denmark (Copenhagen Hospital Biobank, Danish Blood Donor Study, and SupraGen/the Danish General Suburban Population Study [GESUS]), the US (Intermountain Healthcare), and the United Kingdom (UK Biobank) were included. Time of phenotype data collection ranged from January 1983 to December 2022. Data were analyzed from August 2022 to January 2024. Exposures: Sequence variants. Main Outcomes and Measures: Genome-wide significant association of sequence variants with APs. Results: The GWAS included 2310 individuals with APs (median [IQR] age, 43 [28-57] years; 1252 [54.2%] male and 1058 [45.8%] female) and 1 206 977 control individuals (median [IQR] year of birth, 1955 [1945-1970]; 632 888 [52.4%] female and 574 089 [47.6%] male). Of the individuals with APs, 909 had been confirmed in EP study. Three common missense variants were associated with APs, in the genes CCDC141 (p.Arg935Trp: adjusted odds ratio [aOR], 1.37; 95% CI, 1.24-1.52, and p.Ala141Val: aOR, 1.55; 95% CI 1.34-1.80) and SCN10A (p.Ala1073Val: OR, 1.22; 95% CI, 1.15-1.30). The 3 variants associated with PSVT and the SCN10A variant associated with AF, supporting an effect on AP-affiliated arrhythmias. All 3 AP risk alleles were associated with higher heart rate and shorter PR interval, and have reported associations with chronotropic response. Conclusions and Relevance: Associations were found between sequence variants and APs that were also associated with risk of PSVT, and thus likely atrioventricular reentrant tachycardia, but had allele-specific associations with AF and conduction disorders. Genetic variation in the modulation of heart rate, chronotropic response, and atrial or atrioventricular node conduction velocity may play a role in the risk of AP-affiliated arrhythmias. Further research into CCDC141 could provide insights for antiarrhythmic therapeutic targeting in the presence of an AP.

Long-term adherence to a wearable for continuous behavioural activity measuring in the SafeHeart implantable cardioverter defibrillator population.

Aims: Wearable health technologies are increasingly popular. Yet, wearable monitoring only works when devices are worn as intended, and adherence reporting lacks standardization. In this study, we aimed to explore the long-term adherence to a wrist-worn activity tracker in the prospective SafeHeart study and identify patient characteristics associated with adherence. Methods and results: This study enrolled 303 participants, instructed to wear a wrist-worn accelerometer day and night for 6 months. Long-term adherence was defined as valid days (≥22 h of wear time) divided by expected days, and daily adherence as mean hours of wear time per 24 h period. Optimal, moderate, and low long-term and daily adherence groups were defined as long-term adherence above or below 95 and 75% and daily adherence above or below 90 and 75%. Regression models were used to identify patient characteristics associated with long-term adherence. In total, 296 participants [median age 64 years; interquartile range (IQR) 57-72; 19% female] were found eligible, yielding 44 003 days for analysis. The median long-term adherence was 88.2% (IQR 74.6-96.5%). A total of 83 (28%), 127 (42.9%), and 86 (29.1%) participants had optimal, moderate, and low long-term adherence, and 163 (55.1%), 87 (29.4%), and 46 (15.5%) had optimal, moderate, and low daily adherence, respectively. Age and smoking habits differed significantly between adherence levels, and increasing changeover intervals improved the degree of long-term adherence. Conclusion: Long-term adherence to a wearable activity tracker was 88.2% over a 6-month period. Older age and longer changeover interval were positively associated with long-term adherence. This serves as a benchmark for future studies that rely on wearable devices. Trial registration number: The National Trial Registration number: NL9218 (https://onderzoekmetmensen.nl/).

Effects of atrial fibrillation screening according to thyroid function: Post-hoc analysis of the randomized LOOP study.

PURPOSE: Subclinical thyroid dysfunction is a marker for atrial fibrillation (AF) and stroke risk. This study explored the effects of AF screening according to thyroid-stimulating hormone (TSH) levels. METHODS: An AF screening trial (the LOOP study) was analyzed post-hoc according to baseline TSH. The primary outcome was stroke or systemic embolism (SE). Secondary outcomes included major bleeding, all-cause death, and the combination of stroke, SE, and cardiovascular death. RESULTS: TSH measurement was available in 6003 of 6004 trial participants, 1500 randomized to implantable loop recorder (ILR) screening for AF and anticoagulation upon detection vs. 4503 to usual care; mean age was 74.7±4.1 years and 2836 (47%) were women. AF detection was approximately triple for ILR vs usual care across TSH tertiles (adjusted p-interaction=0.44). In the first tertile, screening was associated with decreased risk of the primary outcome (hazard ratio 0.52 [0.30-0.90]; p=0.02) and stroke, SE, or cardiovascular death (hazard ratio 0.54 [0.34-0.84]; p=0.006) compared to usual care, while no effect was observed among participants with higher TSH (adjusted p-interaction 0.03 and 0.01, respectively). There was no effect on other outcomes. Analyses of continuous TSH or excluding those with abnormal TSH or thyroid medication showed similar results. CONCLUSION: AF screening and subsequent treatment was associated with decreased stroke risk among participants with low TSH, though the yield of screening was similar across TSH levels. TSH may be useful as a marker to indicate benefit from AF screening vs. overdiagnosis and overtreatment. These findings should be considered exploratory and warrant further study. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT0203645.

The budget impact of implementing atrial fibrillation-screening in European countries.

A budget impact analysis estimates the short-term difference between the cost of the current treatment strategy and a new treatment strategy, in this case to implement population screening for atrial fibrillation (AF). The aim of this study is to estimate the financial impact of implementing population-based AF-screening of 75-year-olds compared with the current setting of no screening from a healthcare payer perspective in eight European countries. The net budget impact of AF-screening was estimated in country-specific settings for Denmark, Germany, Ireland, Italy, Netherlands, Serbia, Spain, and Sweden. Country-specific parameters were used to allow for variations in healthcare systems and to reflect the healthcare sector in the country of interest. Similar results can be seen in all countries AF-screening incurs savings of stroke-related costs since AF treatment reduces the number of strokes. However, the increased number of detected AF and higher drug acquisition will increase the drug costs as well as the costs of physician- and control visits. The net budget impact per invited varied from €10 in Ireland to €122 in the Netherlands. The results showed the increased costs of implementing AF-screening were mainly driven by increased drug costs and screening costs. In conclusion, across Europe, though the initial cost of screening and more frequent use of oral anti-coagulants will increase the healthcare payers' costs, introducing population screening for AF will result in savings of stroke-related costs.

Incidence and risk factors for first and recurrent ICD shock therapy in patients with an implantable cardioverter defibrillator.

BACKGROUND: Advances in medical treatment and outcomes in implantable cardioverter-defibrillator (ICD) recipients incentivize a need for improved candidate selection and identification of risk factors for ICD therapy. We examined contemporary rates of and risk factors for ICD therapy. METHODS: Patients with ICD for primary (PP) or secondary prevention (SP), implanted between January 2010 and December 2020, were followed for appropriate and inappropriate incident and recurrent shock. RESULTS: Overall, 2998 patients (mean age 61.8 ± 12.7 years, 20% female, 73% ICD carriers, and 47.1% SP) were analyzed with a median follow-up of 4.3 (interquartile range (IQR) 2.1-7.4) years. A total of 426/2998 (14.2%) patients had shock; 364/2998 (12.1%) had appropriate and 82/2998 (2.7%) inappropriate shock, with annualized event rates of 2.34 (2.11-2.59) and 0.49 (0.39-0.61) per 100 person-years, respectively. Of those with shock, 133/364 (36.5%) experienced recurrent appropriate shock and 8/364 (2.2%) received recurrent inappropriate shock, with event rates of 10.57 (8.85-12.53) and 0.46 (0.20-0.92), respectively. In multivariable analyses, female sex was associated with a reduced risk of incident appropriate shock (hazard ratio 0.69 [95% confidence interval 0.52; 0.91]). Of other variables, only revascularization status was associated with recurrent appropriate shock in PP, and CRT-D with recurrent appropriate shock in the overall cohort. CONCLUSION: One in eight ICD recipients received appropriate shock 2-7 years after guideline-directed implantation. More than one-third of patients with a first shock experienced recurrent shock. Few clinical variables showed potential in predicting shocks, illustrating a need for more advanced tools to select candidates for implantation.

Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study.

BACKGROUND: Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown. METHODS: The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in older individuals with additional stroke risk factors. In this secondary analysis, we explored the following HF end points: (1) HF event or cardiovascular death; (2) HF event; (3) event with HF with reduced ejection fraction (HFrEF); and (4) HFrEF event or cardiovascular death. Outcomes were assessed in a Cox model both as time-to-first events and as total (first and recurrent) events analyzed using the Andersen-and-Gill method. RESULTS: Of 6004 participants (mean age 74.7 and 52.7% men), 1501 were randomized to ILR screening and 4503 to the control group. In total, 77 (5.1%) in the ILR group versus 295 (6.6%) in the control group experienced the primary outcome of an HF event or cardiovascular death. Compared with usual care, ILR screening was associated with a nonsignificant reduction in the primary outcome for the time-to-first event analysis (hazard ratio, 0.78 [95% CI, 0.61-1.01]) and the total event analysis (hazard ratio, 0.77 [95% CI, 0.59-1.01]). Similar results were obtained for the HF event. A significant risk reduction in total events was observed in the ILR group for the composite of HFrEF event or cardiovascular death and for HFrEF event (hazard ratio, 0.74 [95% CI, 0.56-0.98] and 0.65 [95% CI, 0.44-0.97], respectively). CONCLUSIONS: In an older population with additional stroke risk factors, ILR screening for atrial fibrillation tended to be associated with a lower rate of total HF events and cardiovascular death, particularly those related to HFrEF. These findings should be considered hypothesis-generating and warrant further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Continuous heart monitoring to evaluate treatment effects in pulmonary hypertension.

BACKGROUND: The treatment of pulmonary hypertension (PH) has improved rapidly in recent decades. There is increasing evidence to support the role of early intervention and treatment in affecting clinical outcomes in PH. OBJECTIVES: To assess treatment effects before and after the escalation of specific PH treatments using continuous heart monitoring with a Reveal LINQ loop recorder. METHODS: Patients were compared before and after treatment escalation. Treatment escalation was defined as an additional pulmonary arterial hypertension (PAH) drug, pulmonary endarterectomy, percutaneous balloon angioplasty or bilateral lung transplantation. Specifically, changes in heart rate variability (HRV), heart rate (HR) and physical activity were assessed. RESULTS: In this prospective study, 41 patients (27 with PAH and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)) were enrolled. Among them, 15 (36.6%) patients underwent PH treatment escalation. Prior to escalation, patients were monitored for a median of 100 (range: 68-100) days and after therapy escalation for a median duration of 165 (range: 89-308) days. In the escalation group, there was a significant increase in HRV, physical activity indexed by daytime HR and a significant decrease in nighttime HR assessed at baseline and after treatment escalation in both the PAH and CTEPH groups. This was paralleled by significant improvements in WHO functional class, 6-min walking distance and N-terminal pro-b-type natriuretic peptide. CONCLUSIONS: This is the first study to demonstrate an association between specific PH therapies and changes in HRV, HR nighttime and physical activity. This indicates the potential of continuous monitoring in the evaluation of treatment effects in PH.

Risk of heart failure among individuals tested for Borrelia burgdorferi sensu lato antibodies, and serum Borrelia burgdorferi sensu lato seropositive individuals; a nationwide population-based, registry-based matched cohort study.

BACKGROUND: Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi (Bb) sensu lato complex. Previous studies have suggested an association between Lyme borreliosis and heart failure, which have been suggested to be a possible manifestation of Lyme carditis. We aimed to investigate the risk of heart failure among individuals tested for serum Bb antibodies, and serum Bb seropositive individuals. METHODS: We performed a matched nationwide cohort study (Denmark, 1993-2020) and included 52,200 Bb seropositive individuals, and two age- and sex-matched comparison cohorts: 1) 104,400 Bb seronegative comparison cohort members, and 2) 261,000 population controls. We investigated the risk associated with 1) being tested for serum Bb antibodies, and 2) being Bb seropositive. Outcomes were: 1) a composite of heart failure, cardiomyopathy, and/or myocarditis diagnosis, and 2) redemption of cardiovascular medicine used for treatment of heart failure. We calculated short-term odds ratios (aOR) (within 1 month) and long-term hazard rates (aHR) (after 1 month) adjusted for age, sex, diabetes, pre-existing heart failure, and kidney disease. RESULTS: Compared with the population controls, individuals tested for Bb antibodies, regardless of the test result, had increased short-term risk of heart failure, cardiomyopathy, and myocarditis (aOR 8.3, 95 %CI: 6.7-10.2), and both increased short- and long-term risk of redemption of cardiovascular medicine (aOR 4.3, 95 %CI: 3.8-4.8, aHR 1.13, 95 % CI: 1.11-1.15). The Bb seropositive individuals had no increased short- or long-term risk of any outcome compared with Bb seronegative comparison cohort members. CONCLUSIONS: In conclusion, Bb antibody tests seemed to be performed in the diagnostic work-up of heart failure, but Bb seropositivity was not associated with heart failure.

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.

Risk of cardiac conduction disorders, and pacemaker implantations among individuals tested for serum Borrelia burgdorferi antibodies, a nationwide, matched, population-based cohort study.

OBJECTIVES: To investigate the short- and long-term risks of atrioventricular block and other cardiac conduction disorders associated with being tested for Borrelia burgdorferi (Bb) antibodies or Bb seropositivity as measures of confounding by indication and Bb infection, respectively. METHODS: We performed a nationwide population-based matched cohort study (Denmark, 1993-2021). We included 52 200 Bb-seropositive individuals (stratified as only Bb-IgM-seropositive [n = 26 103], only Bb-IgG-seropositive [n = 18 698], and Bb-IgM-and-IgG-seropositive [n = 7399]) and two age- and sex-matched comparison cohorts: 104 400 Bb-seronegative individuals and 261 000 population controls. We investigated the risk associated with being tested for serum Bb antibodies and being Bb seropositive. Outcomes were atrioventricular block and other conduction disorders. We calculated short-term odds ratios (aOR) (within 1 month), and long-term hazard ratios (aHR) (after 1 month) adjusted for age, sex, diabetes, chronic heart failure, and kidney disease with 95% CI. RESULTS: Compared with population controls, individuals tested for Bb antibodies had increased short- and long-term risks of atrioventricular block (aOR 47.9, 95% CI: 30.0-76.7, aHR 1.3, 95% CI:1.2-1.3), and other conduction disorders (aOR 18.2, 95% CI: 10.1-32.8, aHR 1.2, 95% CI: 1.1-1.4). Compared with Bb-seronegative individuals, only Bb-IgM-and-IgG-seropositive individuals had increased short-term risk of atrioventricular block (aOR: 2.1, 95% CI: 1.5-3.1). DISCUSSION: The results suggest that Bb antibody testing is included in the diagnostic work-up of conduction disorders. Finally, that Bb seropositivity is not associated with other conduction disorders than atrioventricular block or with increased long-term risk of conduction disorders.

Association between QRS shortening and mortality after cardiac resynchronization therapy: Results from the DANISH study.

BACKGROUND: Changes in QRS duration (∆QRS) are often used in the clinical setting to evaluate the effect of cardiac resynchronization therapy (CRT), although an association between ∆QRS and outcomes is not firmly established. We aimed to assess the association between mortality and ∆QRS after CRT in patients from the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-Ischemic Systolic Heart Failure on Mortality) study. METHODS: We included all patients from DANISH who received a CRT device and had available QRS duration data before and after implantation. Cox proportional hazards models were used to assess associations between ∆QRS (post-CRT QRS minus pre-CRT QRS) and mortality. RESULTS: Complete data were available in 572 patients. Median baseline QRS duration was 160 ms (IQR [146;180]). Post-CRT QRS was recorded a median of 48 days (IQR [33;86]) after implantation, and the median ∆QRS was -14 ms (IQR [-38;-3]). During a median follow-up of 4.1 years (IQR [2.5;5.8]), 106 patients died. In crude Cox regression, all-cause mortality was reduced by 6% per 10 ms shortening of QRS (HR 0.94; CI: 0.88-1.00, p = 0.04). The effect did not remain significant after multivariable adjustment (HR 1.01, CI: 0.93-1.10, p = 0.77). Further, no association was found between ∆QRS and improvement of New York Heart Association functional class at 6 months (OR 1.03, CI: 0.96-1.10, p = 0.42). CONCLUSION: In a large cohort of patients with non-ischemic cardiomyopathy, reduction of QRS duration after CRT was not associated with changes in mortality during long-term 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.

Association between myocardial work indices and cardiovascular events according to hypertension in the general population.

AIMS: Pressure-strain loop (PSL) analysis is a novel echocardiographic tool capable of assessing myocardial work non-invasively. In this study, we aim to evaluate the prognostic value of myocardial work indices in the general population. METHODS AND RESULTS: This was a prospective community-based cohort study (n = 4466). PSL analyses were performed to acquire global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency (GWE). The endpoint was a composite of heart failure or cardiovascular death (HF/CVD). Survival analysis was applied. A total of 3932 participants were included in this analysis (median age: 58 years, 43% men). Of these, 124 (3%) experienced the outcome during a median follow-up period of 3.5 years [interquartile range (IQR): 2.6-4.4 years]. Hypertension significantly modified the association between all work indices and outcome (P for interaction < 0.05), such that work indices posed a higher risk of outcome in non-hypertensive than in hypertensive participants. After adjusting for Atherosclerosis Risk in Communities (ARIC)-HF risk variables, all work indices predicted outcome in non-hypertensive participants, but only GWI, GCW, and GWE predicted outcome in hypertensive participants [GWI: hazard ratio (HR) = 1.12 (1.07-1.16), per 100 mmHg% decrease; GCW: HR = 1.12 (1.08-1.17), per 100 mmHg% decrease; GWE: HR = 1.08 (1.04-1.12), per 1% decrease]. Only GWE significantly increased C-statistics when added to ARIC-HF risk variables in hypertensive participants (C-stat 0.865 vs. 0.877, P for increment = 0.003). CONCLUSION: Hypertension modifies the association between myocardial work indices and HF/CVD in the general population. All work indices are associated with outcome in normotensive participants. GWI, GCW, and GWE are independently associated with outcome in hypertension, but only GWE improves risk prediction.