Comprehensive Evaluation of Rhythm Monitoring Strategies in Screening for Atrial Fibrillation: Insights From Patients at Risk Monitored Long Term With an Implantable Loop Recorder.

BACKGROUND: Stroke is an increasing health problem worldwide. Atrial fibrillation (AF) is a major risk factor for stroke, and the attention given to AF screening is rising, as new monitoring technologies emerge. We aimed to evaluate the performance of a large panel of screening strategies and to assess population characteristics associated with diagnostic yield. METHODS: Individuals with stroke risk factors but without AF were recruited from the general population to undergo screening with an implantable loop recorder. New-onset AF lasting ≥6 minutes was adjudicated by senior cardiologists. After continuous monitoring for >3 years, complete day-to-day heart rhythm data sets were reconstructed for every participant, including exact time of onset and termination of all AF episodes. Random sampling was applied to assess the sensitivity and negative predictive value of screening with various simulated screening strategies compared with the implantable loop recorder. The diagnostic yield across strategies and population subgroups was compared by use of nonparametric tests. RESULTS: The rhythm data sets comprised 590 participants enduring a total of 659 758 days of continuous monitoring and 20 110 AF episodes. In these data, a single 10-second ECG yielded a sensitivity (and negative predictive value) of 1.5% (66%) for AF detection, increasing to 8.3% (67%) for twice-daily 30-second ECGs during 14 days and to 11% (68%), 13% (68%), 15% (69%), 21% (70%), and 34% (74%) for a single 24-hour, 48-hour, 72-hour, 7-day, or 30-day continuous monitoring, respectively. AF detection further improved when subsequent screenings were performed or when the same monitoring duration was spread over several periods compared with a single period (eg, three 24-hour monitorings versus one 72-hour monitoring; P<0.0001 for all comparisons). The sensitivity was consistently higher among participants with age ≥75 years, male sex, CHADS2 score >2, or NT-proBNP (N-terminal pro-B-type natriuretic peptide) ≥40 pmol/L and among participants with underlying ≥24-hour AF episodes compared with shorter AF (P<0.0001 for all screening strategies). CONCLUSIONS: In screening for AF among participants with stroke risk factors, the diagnostic yield increased with duration, dispersion, and number of screenings, although all strategies had low yield compared with the implantable loop recorder. The sensitivity was higher among participants who were older, were male, or had higher NT-proBNP. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Incidence and predictors of atrial fibrillation episodes as detected by implantable loop recorder in patients at risk: From the LOOP study.

BACKGROUND: Recent studies have suggested a high prevalence of subclinical atrial fibrillation (AF) in various patient populations, and interest in AF screening has increased. However, knowledge about episode duration is scarce, and risk factors for short or long subclinical AF episodes have yet to be recognized. The aim of the study was to assess AF by long-term continuous screening and to investigate predictors of episodes lasting ≥6 minutes, ≥5.5 hours, or ≥24 hours, respectively. METHODS: A total of 597 patients aged ≥70 years and diagnosed with ≥1 of hypertension, diabetes, previous stroke, or heart failure were recruited from the general population to receive implantable loop recorder with remote monitoring. Exclusion criteria included history of AF or cardiac implantable electronic device. AF episodes were adjudicated by senior cardiologists. RESULTS: During 40 (37; 42) months of continuous monitoring, AF was detected in 209 (35%) of the patients. The cumulative incidences at 3 years were 33.8% (30.2%-37.8%), 16.1% (13.4%-19.4%), and 5.7% (4.1%-7.9%) for AF episodes lasting ≥6 minutes, ≥5.5 hours, and ≥24 hours, respectively. Slower resting sinus rate and higher body mass index, N-terminal prohormone of brain natriuretic peptide, and troponin T at baseline were independently associated with AF detection. Addition of these markers to a model of sex, age, and comorbidities improved prediction of AF episodes ≥24 hours (time-dependent area under the receiver operating characteristic curve 79% vs 65%, P = .037). CONCLUSIONS: A considerable burden of previously unknown AF was detected when long-term monitoring was applied in at-risk patients. Biomarkers were associated with AF incidence and improved prediction of long AF episodes.

Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Although it has been widely appreciated that obesity is a major risk factor for CVD, treatments that produce effective, durable weight loss and the impact of weight reduction in reducing cardiovascular risk have been elusive. Instead, progress in CVD risk reduction has been achieved through medications indicated for controlling lipids, hyperglycemia, blood pressure, heart failure, inflammation, and/or thrombosis. Obesity has been implicated as promoting all these issues, suggesting that sustained, effective weight loss may have independent cardiovascular benefit. GLP-1 receptor agonists (RAs) reduce weight, improve glycemia, decrease cardiovascular events in those with diabetes, and may have additional cardioprotective effects. The GLP-1 RA semaglutide is in phase 3 studies as a medication for obesity treatment at a dose of 2.4 mg subcutaneously (s.c.) once weekly. Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) is a randomized, double-blind, parallel-group trial testing if semaglutide 2.4 mg subcutaneously once weekly is superior to placebo when added to standard of care for preventing major adverse cardiovascular events in patients with established CVD and overweight or obesity but without diabetes. SELECT is the first cardiovascular outcomes trial to evaluate superiority in major adverse cardiovascular events reduction for an antiobesity medication in such a population. As such, SELECT has the potential for advancing new approaches to CVD risk reduction while targeting obesity.

Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials.

BACKGROUND: Semaglutide is a glucagon-like peptide-1 (GLP-1) analog treatment for type 2 diabetes (T2D) available in subcutaneous (s.c.) and oral formulations. Two cardiovascular (CV) outcomes trials showed that in subjects with T2D at high risk of CV events there were fewer major adverse CV events (MACE; defined as CV death, non-fatal stroke, non-fatal myocardial infarction) with semaglutide than with placebo (hazard ratio [95% CI]: 0.74 [0.58;0.95] for once-weekly s.c. semaglutide and 0.79 [0.57;1.11] for once-daily oral semaglutide). However, there is little evidence for an effect of semaglutide on MACE in subjects not at high risk of CV events. This post hoc analysis examined CV effects of semaglutide in subjects across a continuum of baseline CV risk. METHODS: Data from the s.c. (SUSTAIN) and oral (PIONEER) semaglutide phase 3a clinical trial programs were combined according to randomized treatment (semaglutide or comparators) and analyzed to assess time to first MACE and its individual components. A CV risk model was developed with independent data from the LEADER trial (liraglutide vs placebo), considering baseline variables common to all datasets. Semaglutide data were analyzed to assess effects of treatment as a function of CV risk predicted using the CV risk prediction model. RESULTS: The CV risk prediction model performed satisfactorily when applied to the semaglutide data set (area under the curve: 0.77). There was a reduced relative and absolute risk of MACE for semaglutide vs comparators across the entire continuum of CV risk. While the relative risk reduction tended to be largest with low CV risk score, the largest absolute risk reduction was for intermediate to high CV risk score. Similar results were seen for relative risk reduction of the individual MACE components and also when only placebo comparator data were included. CONCLUSION: Semaglutide reduced the risk of MACE vs comparators across the continuum of baseline CV risk in a broad T2D population. Trial registrations ClinicalTrials.gov identifiers: NCT02054897, NCT01930188, NCT01885208, NCT02128932, NCT02305381, NCT01720446, NCT02207374, NCT02254291, NCT02906930, NCT02863328, NCT02607865, NCT02863419, NCT02827708, NCT02692716, NCT02849080, NCT03021187, NCT03018028, NCT03015220.

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

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

Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials.

AIMS: To assess the effect of baseline body mass index (BMI) and the occurrence of nausea and/or vomiting on weight loss induced by semalgutide, a once-weekly glucagon-like peptide 1 analogue for the treatment of type 2 diabetes. Semaglutide demonstrated superior reductions in HbA1c and superior weight loss (by 2.3-6.3 kg) versus different comparators across the SUSTAIN 1 to 5 trials; the contributing factors to weight loss are not established. MATERIALS AND METHODS: Subjects with inadequately controlled type 2 diabetes (drug-naïve or on background treatment) were randomized to subcutaneous semaglutide 0.5 mg (excluding SUSTAIN 3), 1.0 mg (all trials), or comparator (placebo, sitagliptin, exenatide extended release or insulin glargine). Subjects were subdivided by baseline BMI and reporting (yes/no) of any nausea and/or vomiting. Change from baseline in body weight was assessed within each trial and subgroup. A mediation analysis separated weight loss into direct or indirect (mediated by nausea or vomiting) effects. RESULTS: Clinically relevant weight-loss differences were observed across all BMI subgroups, with a trend towards higher absolute weight loss with higher baseline BMI. Overall, 15.2% to 24.0% and 21.5% to 27.2% of subjects experienced nausea or vomiting with semaglutide 0.5 and 1.0 mg, respectively, versus 6.0% to 14.1% with comparators. Only 0.07 to 0.5 kg of the treatment difference between semaglutide and comparators was mediated by nausea or vomiting (indirect effects). CONCLUSIONS: In SUSTAIN 1 to 5, semaglutide-induced weight loss was consistently greater versus comparators, regardless of baseline BMI. The contribution of nausea or vomiting to this weight loss was minor.

Atrial fibrillation detected by continuous electrocardiographic monitoring using implantable loop recorder to prevent stroke in individuals at risk (the LOOP study): Rationale and design of a large randomized controlled trial.

Atrial fibrillation (AF) increases the rate of stroke 5-fold, and AF-related strokes have a poorer prognosis compared with non-AF-related strokes. Atrial fibrillation and stroke constitute an intensifying challenge, and health care organizations are calling for awareness on the topic. Previous studies have demonstrated that AF is often asymptomatic and consequently undiagnosed. The implantable loop recorder (ILR) allows for continuous, long-term electrocardiographic monitoring with daily transmission of arrhythmia information, potentially leading to improvement in AF detection and stroke prevention. METHODS: The LOOP study is an investigator-initiated, randomized controlled trial with 6,000 participants randomized 3:1 to a control group or to receive an ILR with continuous electrocardiographic monitoring. Participants are identified from Danish registries and are eligible for inclusion if 70years or older and previously diagnosed as having at least one of the following conditions: hypertension, diabetes mellitus, heart failure, or previous stroke. Exclusion criteria include history of AF and current oral anticoagulation treatment. When an AF episode lasting ≥6minutes is detected, oral anticoagulation will be initiated according to guidelines. Expected follow-up is 4years. The primary end point is time to stroke or systemic embolism, whereas secondary end points include time to AF diagnosis and death. CONCLUSION: The LOOP study will evaluate health benefits and cost-effectiveness of ILR as a screening tool for AF to prevent stroke in patients at risk. Secondary objectives include identification of risk factors for the development of AF and characterization of arrhythmias in the population. The trial holds the potential to influence the future of stroke prevention.

Epilepsy and risk of death and sudden unexpected death in the young: a nationwide study.

PURPOSE: Patients with epilepsy are at increased risk of premature death from all causes and likely also from sudden unexplained death (SUD). Many patients with epilepsy have significant comorbidity, and it is unclear how much of the increased risk can be explained by epilepsy itself. We aimed to chart the incidence of sudden unexpected death in epilepsy (SUDEP) and estimate the risk of death from all causes and SUD conferred by epilepsy independently. METHODS: We conducted a historical cohort study using data from Danish registries and a complete manual review of all death certificates. The population studied consisted of all Danish residents in the age group 1-35 years, in the period 2000-2006 (inclusive), and the main outcome measures were risk of death and SUD. KEY FINDINGS: We identified 33,022 subjects with epilepsy (median follow-up 3.7 years) and 3,001,952 subjects without (median follow-up 7.0 years). Among 685 deaths in the population with epilepsy, we identified 50 cases of definite and probable SUDEP corresponding to an incidence rate of 41.1 (95% confidence interval [CI] 31.6-54.9) per 100,000 person-years. Incidence rates increased with age from 17.6 (95% CI 9.5-32.8) in the age group 1-18 years to 73.8 (95% CI 52.5-103.8) for the age group 24-35 years. Having epilepsy increased the crude risk of death with a hazard ratio (HR) of 11.9 (95% CI 11.0-12.9). When adjusting for sex and comorbidities often encountered in patients with epilepsy (neurologic disease including cerebral palsy, psychiatric disease including mental retardation, and congenital disorders), as well as the Charlson comorbidity score, the HR fell to 5.4 (95% CI 4.9-6.0). The crude HR for SUD was 27.5 (95% CI 18.1-41.8) and fell to 16.3 (95% CI 9.8-26.9) when adjusted for the same covariates as above. SIGNIFICANCE: Epilepsy in and of itself carries a significant risk of premature death and SUD. These findings highlight the potential gains of risk factor modification for the prevention of premature death and SUDEP in patients with epilepsy.

Prior myocardial infarction in the young: predisposes to a high relative risk but low absolute risk of a sudden cardiac death.

AIMS: The study reports the relative and absolute risk of sudden cardiac death (SCD) in patients <36 years with prior myocardial infarction (MI). METHODS AND RESULTS: Through review of death certificates, we identified all SCDs in Danes aged 18-35 years between 1 January 2000 until 31st December 2006. We then used the unique Danish civil registration number, which enabled us to follow all Danes in national registries, in the same period. Through the National Patient Registry we identified those with a prior myocardial infarction [implantable cardioverter defibrillator (ICD)-8: 410, ICD-10: I21 and I22] and incidence rates for SCD were estimated for survivors of MI and for individuals who had not yet suffered an MI, respectively. We estimated the relative risk of SCD and all-cause mortality by using extended Cox regression models. The 1,862,431 Danes aged between 18 and 35 years were followed in 9,388,453 person-years between 2000 and 2006. There were 7434 deaths of which 387 (5.2%) were SCDs. Myocardial infarction was diagnosed in 1234 patients, of those 10 died of SCD. Prior MI increased the incidence rate of SCD from 4.1 to 305.0 per 100,000 person-years [95% confidence interval (CI): 164.1-567.0]. Myocardial infarction was correlated with SCD and all-cause mortality, with a hazard ratio (HR) of 55.5 (95% CI: 29.5-104.4), P< 0.0001 and HR 8.3 (95% CI: 6.0-11.3), P< 0.0001, respectively. CONCLUSION: We report that prior MI at a young age significantly increases SCD incidence from 4.1 to 305.0 per 100,000 person-years. Myocardial infarction is furthermore correlated with SCD and all-cause mortality with HR of 55.5 and 8.3, respectively.

Differences in investigations of sudden unexpected deaths in young people in a nationwide setting.

BACKGROUND: Inherited disease may be causative in many young sudden unexpected death cases. Autopsy is essential in the counselling of the bereaved, as the family of the victim may be at risk too. In a nationwide setting operating under the same set of laws, we hypothesized that regional differences exist in the investigation of young persons dying suddenly and unexpectedly. METHODS AND RESULTS: All deaths in persons aged 1-35 years in Denmark in 2000-2006 were included. Death certificates were read independently by two physicians. External examination as well as autopsy status was retrieved. Significant regional differences were found regarding external examinations and autopsy frequencies. Ratios of conducted external examinations varied between 63% and 93% (p = 0.004). Autopsy ratios varied between 60% and 88% (p = 0.001). In urban areas, external examinations and autopsies were more often conducted than in rural areas. In East Denmark, there were more external examinations resulting in a forensic autopsy, and there was a higher overall autopsy rate compared to West Denmark. CONCLUSION: Despite operating under the same set of laws, we document significant regional differences in forensic investigations of young persons suffering a sudden unexpected death. This is probably not unique for Denmark although no data exist to confirm that. The results are worrying and call for a revision of the way these deaths are handled. Mandatory autopsy in sudden unexpected death in young persons is warranted as a thorough investigation of the death may help the clinician in guidance of the relatives in relation to hereditary diseases.

Low disease prevalence and inappropriate implantable cardioverter defibrillator shock rate in Brugada syndrome: a nationwide study.

AIMS: Brugada syndrome (BrS) is an inherited channelopathy that predisposes to malignant ventricular arrhythmias and thereby syncope and sudden cardiac death. Prior studies characterizing BrS patients have used highly selected referral populations from tertiary centres and prevalence estimates have been carried out using electrocardiogram (ECG) surveys only. We aimed to identify and characterize all diagnosed BrS patients in Denmark (population 5.4 million). METHODS AND RESULTS: Brugada syndrome patients were identified using several modalities including identification in all Danish tertiary referral centres, search in public health registries, contact to all cardiology departments in Denmark, and searching in a pedigree database for inherited heart disease used nationwide in Denmark. We identified 43 definite diagnosed BrS patients and 25 possible BrS patients, corresponding to a prevalence of 1.1 definite BrS cases per 100 000 inhabitants. Most definite BrS patients were men (86%) and the median age at diagnosis was 48 years. A total of 35 definite BrS patients (81%) had an implantable cardioverter defibrillator (ICD) implanted and of these 9 (26%) experienced appropriate shocks and 3 (8%) experienced inappropriate shocks during a median follow-up of 47 months. No patient died or experienced aborted sudden cardiac death during follow-up. CONCLUSIONS: We report the first nationwide study of BrS patients. We found a low incidence of diagnosed definite BrS compared with estimates from ECG surveys. Follow-up data show a lower rate of inappropriate therapies in ICD carriers than that reported in previous studies.

Nationwide study of sudden cardiac death in persons aged 1-35 years.

AIMS: The aim of this investigation was to study the incidence of sudden cardiac death (SCD) in persons aged 1-35 years in a nationwide setting (5.38 million people) by systematic evaluation of all deaths. METHODS AND RESULTS: All deaths in persons aged 1-35 years in Denmark in 2000-06 were included. Death certificates were read independently by two physicians. The National Patient Registry was used to retrieve information on prior medical history. All autopsy reports were read and the cause of death was revised based on autopsy findings. We identified 625 cases of sudden unexpected death (10% of all deaths), of which 156 (25%) were not autopsied. Of the 469 autopsied cases, 314 (67%) were SCD. The most common cardiac cause of death was ischaemic heart disease (13%); 29% of autopsied sudden unexpected death cases were unexplained. In 45% of SCD cases, the death was witnessed; 34% died during sleep; 89% were out-of-hospital deaths. Highest possible incidence rate of SCD in the young was 2.8 per 100 000 person-years including non-autopsied cases of sudden unexpected death. Excluding those, the incidence rate declined to 1.9 per 100 000 person-years. CONCLUSIONS: A total of 7% of all deaths in the young can be attributed to SCD, when including non-autopsied cases (autopsy ratio 75%). The incidence rate of SCD in the young of 2.8 per 100 000 person-years is higher than previously reported.

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

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

Incomplete right bundle branch block: a novel electrocardiographic marker for lone atrial fibrillation.

AIMS: P-wave morphology and PR interval have both been previously associated with atrial fibrillation (AF). We hypothesized that incomplete right bundle branch block (IRBBB) would be associated with early-onset lone AF. METHODS AND RESULTS: We conducted a case-control study comparing electrocardiographic (ECG) markers from patients with early-onset lone AF and from a healthy control population. We included 187 patients with early-onset lone AF and 383 healthy controls. Sixty-two lone AF patients were excluded from the study because of AF at the time of enrolment or because of the use of antiarrhythmic drugs. For the remaining 125 patients with paroxysmal or persistent lone AF (84% males, mean age 37), controls were matched on a 1:1 basis on the parameters gender and age. A significantly higher proportion of the lone AF population had an IRBBB compared with the subjects in the control group (33.6 vs. 10.4%; P<0.001). In multivariable analysis adjusted for conventional risk factors, IRBBB was strongly associated with lone AF [odds ratio (OR) 5.43; 95% confidence interval (CI) 2.30-13.02; P<0.001]. Lone AF patients had a significantly longer PR interval than the control group (175.1 vs. 160.9 ms; P<0.001), but in multivariable analysis, every 10 ms increase in the PR interval was only borderline significantly associated with an OR of 1.15 (95% CI 0.99-1.32; P=0.060) for lone AF. CONCLUSION: We are the first to report that IRBBB is strongly and independently associated with early-onset lone AF.

Sudden unexpected death in infancy in Denmark.

BACKGROUND: Incidence of sudden unexpected death in infancy (SUDI) and sudden infant death syndrome (SIDS) differs among studies and non-autopsied cases are difficult to assess. OBJECTIVES: To investigate causes of sudden death in infancy in a nationwide setting. Validate the use of the ICD-10 code for SIDS (R95) in the Danish Cause of Death registry. DESIGN: A retrospective analysis of all infant deaths (< 1 year of age) in Denmark in 2000-2006. All death certificates and autopsy reports were read. RESULTS: We identified 192 SUDI cases (10% of total deaths, 0.42 per 1000 births) with autopsy performed in 87% of cases. In total, 49% of autopsied SUDI cases were defined as SIDS (5% of all deaths, 0.22 per 1000 births); Cardiac cause of death was denoted in 24% of cases. The Danish Cause of Death Registry misclassified 30% of SIDS cases. CONCLUSIONS: A large proportion of infant deaths are SUDI, and the majority of these are caused by cardiac disease or SIDS. Autopsy is not always performed and valuable information is subsequently lost. Cause of Death registry data is not accurate in describing SIDS.

Comparison of the three-level and the five-level versions of the EQ-5D.

EQ-5D is a generic instrument to measure health-related quality of life. In 2009, a new version, EQ-5D-5L, was introduced as an attempt to reduce ceiling effects and improve sensitivity to small changes over time. The objective of this study was to assess the measurement properties of the EQ-5D-5L instrument compared to the EQ-5D-3L instrument in an elderly general population with a moderate to a high degree of comorbidity. A subgroup of participants in a large clinical trial completed the EQ-5D-3L and the EQ-5D-5L questionnaires. Based on the collected data, we tested for feasibility and ceiling and floor effects. Furthermore, we assessed the redistribution properties of the responses and examined the level of inconsistency, informativity, and convergent validity. A total of 1002 persons diagnosed with hypertension, diabetes, heart failure, and/or previous stroke completed both the EQ-5D-3L and the EQ-5D-5L questionnaires. The overall ceiling effect decreased from 46% with the EQ-5D-3L to 30% with the EQ-5D-5L and absolute and relative informativity were higher for EQ-5D-5L, and there was a stronger correlation between EQ-5D-5L and EQ VAS. The EQ-5D-5L seemed to perform better than the EQ-5D-3L in terms of feasibility, ceiling effect, discriminatory power, and convergent validity. The overall ceiling effect was higher than that found in patient samples in previous studies but lower than the one found in population studies.

Natural History of Subclinical Atrial Fibrillation Detected by Implanted Loop Recorders.

BACKGROUND: As new heart rhythm monitoring technologies emerge, subclinical atrial fibrillation (AF) signifies a future challenge to health care systems. The pathological characteristics of this condition are largely unknown. OBJECTIVES: This study sought to characterize the natural history of subclinical AF in at-risk patients from the general population. METHODS: The authors studied 590 individuals ≥70 years of age with ≥1 of hypertension, diabetes, previous stroke, or heart failure, without history of AF, undergoing long-term implantable loop recorder monitoring as part of the LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals) study. Baseline assessments included N-terminal pro-B-type natriuretic peptide (NT-proBNP). All day-to-day heart rhythm and symptom data were extracted from the device. Endpoints included AF burden, AF progression, symptom reports, and heart rate during AF. RESULTS: A total of 685,445 monitoring days were available for analysis. Adjudicated AF episodes lasting ≥6 min were detected in 205 participants (35%). The AF burden was median 0.13% (interquartile range: 0.03% to 1.05%) of the monitoring time and changed by a factor of 1.31 (95% CI: 1.02 to 1.68) per doubling of NT-proBNP. AF episodes were present 2.7% (interquartile range: 1.0% to 15.7%) of monitoring days after debut. Progression to 24-h episodes was seen in 33 of the AF patients (16%), whereas 46 (22%) had no AF episodes in the last 6 months of monitoring or longer. Symptoms were absent in 185 (90%) at debut, and 178 (87%) never reported AF-related symptoms during follow-up. The averaged heart rate during AF was 96 (interquartile range: 83 to 114) beats/min, 24 (interquartile range: 9 to 41) beats/min faster than daytime sinus rates. CONCLUSIONS: Although previously unknown AF was highly prevalent, the burden was low, and progression was limited. In addition, symptoms were scarce, and the heart rate was only modestly elevated. (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals [LOOP]; NCT02036450).

Primary Prevention of Sudden Cardiac Death With Implantable Cardioverter-Defibrillator Therapy in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Implantable cardioverter-defibrillator (ICD) therapy remains a corner stone of sudden cardiac death (SCD) prevention in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to assess predictors of appropriate ICD therapies in the Scandinavian cohort of ARVC patients who received ICD for primary prevention of SCD. Study group comprised of 79 definite ARVC patients by 2010 Task Force criteria (60% male, age at ICD implant 39 ± 14 years) who were enrolled in the Nordic ARVC Registry and received an ICD for primary SCD prevention. The primary end point of appropriate ICD shock or death from any cause was assessed and compared with 137 definite ARVC patients who received ICD for secondary SCD prevention (74% male, age at ICD implant 42 ± 15 years). In the study group, 38% were ≤35 years of age at baseline, 25% had nonsustained ventricular tachycardia, and 29% had syncope at baseline. Major repolarization abnormality (hazard ratio = 4.00, 95% confidence interval 1.30 to 12.30, p = 0.015) and age ≤35 years (hazard ratio = 4.21, 95% confidence interval 1.49 to 11.85, p = 0.001) independently predicted the primary end point. The outcome did not differ between the primary prevention patients with either of these risk factors and the secondary prevention cohort (2% to 4% annual event rate) whereas patients without risk factors did not have any appropriate ICD shocks during follow-up. In conclusion, young age at ARVC diagnosis and major repolarization abnormality independently predict ICD shocks or death in the primary prevention ICD recipients and associated with the event rate similar to the one observed in the secondary prevention cohort. Our data indicate the benefit of ICD for primary prevention in patients with any of these risk factors.

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

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.

Complications after implantation of a new-generation insertable cardiac monitor: Results from the LOOP study.

BACKGROUND: Insertable cardiac monitors (ICM) are leadless devices utilized in long-term monitoring of the heart rhythm. The implantation procedure of the new-generation ICMs is minimally invasive, but little experience exists regarding complications. We thus aimed to investigate adverse events (AE) according to procedure-related characteristics after implantation of a large number of new-generation ICMs. METHODS: The study population consisted of participants randomized to receive ICM in a multi-center trial. The Reveal LINQ™ ICM was implanted using provided insertion tools, either in an electrophysiology laboratory or outpatient procedure room. If device sensing was insufficient in the first subcutaneous position, one or more repositions were performed. Patients were urged to make contact if they suspected any AE. Furthermore, follow-up for safety endpoints consisted of evaluation of medical records and planned study visits. RESULTS: 1420 patients received an ICM, 753 (53%) in a procedure room and 667 (47%) in an electrophysiology laboratory. During a median follow-up of 499days, 9 (0.63%) and 15 (1.13%) patients experienced AEs with and without need for device explantation, respectively. In the 38 patients requiring device repositioning, more AEs requiring explantation were seen (3 (7.9%) vs. 6 (0.4%), p=0.001). Patients undergoing implantation in a procedure room had more infections (12 (1.6%) vs. 1 (0.1%), p=0.004), though no significant difference was reached in AEs requiring explantation (7 (0.9%) vs. 2 (0.3%), p=0.19). CONCLUSION: The Reveal LINQ™ ICM can be inserted with a very low risk of complications, both in the traditional electrophysiology laboratory setting and in an outpatient procedure room.