A phase 1 trial of AP30663, a K2 channel inhibitor in development for conversion of atrial fibrillation.

Aims: AP30663 is a novel compound under development for pharmacological conversion of atrial fibrillation by targeting the small conductance Ca activated K (K2) channel. The aim of this extension phase 1 study was to test AP30663 at higher single doses compared to the first-in-human trial.

Methods: Sixteen healthy male volunteers were randomized into 2 cohorts: 6- and 8-mg/kg intravenous single-dose administration of AP30663 vs.

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.

Associations between primary care electrocardiography and non-Alzheimer dementia.

Objectives: To determine whether electrocardiogram (ECG) markers are associated with incident non-Alzheimer's dementia (non-AD) and whether these markers also improve risk prediction for non-AD.

Materials And Methods: We retrospectively included 170,605 primary care patients aged 60 years or older referred for an ECG by their general practitioner and followed them for a median of 7.6 years.

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.

Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): a randomised controlled trial.

Background: It is unknown whether screening for atrial fibrillation and subsequent treatment with anticoagulants if atrial fibrillation is detected can prevent stroke. Continuous electrocardiographic monitoring using an implantable loop recorder (ILR) can facilitate detection of asymptomatic atrial fibrillation episodes. We aimed to investigate whether atrial fibrillation screening and use of anticoagulants can prevent stroke in individuals at high risk.

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.

Electrocardiographic T-wave morphology and risk of mortality.

Background: Electrocardiographic T-wave morphology is used in drug safety studies as an adjunct to the QT interval, but few measurements of T-wave morphology can be interpreted in clinical practice. Morphology combination score (MCS) is a combination of T-wave flatness/peakedness, asymmetry, and notching, enabling easy visual assessment of T-wave morphology. We aimed to test the association between T-wave morphology, quantified by MCS, and mortality.

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.

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.

Early glycaemic changes after initiation of oral antidiabetic medication and risk of major adverse cardiovascular events: results from a large primary care population of patients with type 2 diabetes.

Aims: To determine the risk of major adverse cardiovascular events (MACE) and death, associated with an early large and rapid decline in glycated haemoglobin (HbA1C) following first time initiation of an oral antidiabetic drug (OAD).

Methods And Results: We included 10 518 primary care patients with type 2 diabetes, who initiated an OAD for the first time. For each individual, we measured a decline in HbA1C, as the difference between the pre-treatment HbA1C (within 3 months before OAD initiation) and the post-treatment HbA1C (within 1.

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.

Incidence, Predictors, and Success of Ventricular Tachycardia Catheter Ablation in Arrhythmogenic Right Ventricular Cardiomyopathy (from the Nordic ARVC Registry).

Catheter ablation may reduce ventricular tachycardia (VT) burden in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. However, little is known about factors predicting need for ablation. Therefore, we sought to investigate predictors and use of VT ablation and to evaluate the postprocedural outcome in ARVC patients.

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.

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.

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

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

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.

Effect of diabetes duration on the relationship between glycaemic control and risk of death in older adults with type 2 diabetes.

Aim: To investigate the effect of diabetes duration on glycaemic control, measured using mean glycated haemoglobin (HbA1c) level, and mortality risk within different age, sex and clinically relevant, comorbidity-defined subgroups in an elderly population with type 2 diabetes (T2D).

Methods: We studied older (≥65 years) primary care patients with T2D, who had three successive annual measurements of HbA1c taken between 2005 and 2013. The primary exposure was the mean of all three HbA1c measurements.

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

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

Design: Cross-sectional study.

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

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.

Clinical implications of electrocardiographic bundle branch block in primary care.

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

Methods: Retrospective cohort study of primary care patients referred for electrocardiogram (ECG) recording between 2001 and 2011.

Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide.

Context: Semaglutide, a once-weekly glucagon-like peptide-1 analog approved for use in patients with type 2 diabetes (T2D), demonstrated superior body weight (BW) reductions and decreased insulin resistance (IR) vs comparators across the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) 1-3 clinical trials.

Objective: To investigate the relationship between IR and BW across the SUSTAIN 1-3 trials.

Design: Post hoc analysis of the SUSTAIN 1-3 trials.

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.

Visit-to-Visit Variability of Hemoglobin A in People Without Diabetes and Risk of Major Adverse Cardiovascular Events and All-Cause Mortality.

Objective: We aimed to study whether visit-to-visit variability of glycated hemoglobin A (HbA) is associated with incident major adverse cardiovascular events (MACE), all-cause mortality, and type 2 diabetes in people without diabetes.

Research Design And Methods: We included primary care patients with no history of diabetes or cardiovascular disease and with three annual HbA measurements within normal range (<6.5% [48 mmol/mol]).