P-wave characteristics as electrocardiographic markers of atrial abnormality in prediction of incident atrial fibrillation - The Malmö Preventive Project.

BACKGROUND: P-wave indices reflect atrial abnormalities contributing to atrial fibrillation (AF). We aimed to assess a comprehensive set of P-wave characteristics for prediction of incident AF in a population-based setting. METHODS: Malmö Preventative Project (MPP) participants were reexamined in 2002-2006 with electrocardiographic (ECG) and echocardiographic examinations and followed for 5 years. AF-free subjects (n = 983, age 70 ± 5 years, 38% females) with sinus rhythm ECGs were included in the study. ECGs were digitally processed using the Glasgow algorithm. P-wave duration, axis, dispersion, P-terminal force in lead V1 and interatrial block (IAB) were evaluated. ECG risk score combining the morphology, voltage and length of P-wave (MVP score) was calculated. New-onset diagnoses of AF were obtained from nation-wide registers. RESULTS: During follow up, 66 patients (7%) developed AF. After adjustment for age and gender, the independent predictors of AF were abnormal P-wave axis > 75° (HR 1.63 CI95% 1.95-11.03) and MVP score 4 (HR 6.17 CI 95% 1.76-21.64), both correlated with LA area: Person r - 0.146, p < 0.001 and 0.192, p < 0.001 respectively. Advanced IAB (aIAB) with biphasic P-wave morphology in leads III and aVF was the most prevalent variant of aIAB and predicted AF in a univariate model (HR 2.59 CI 95% 1.02-6.58). CONCLUSION: P-wave frontal axis and MVP score are ECG-based AF predictors in the population-based cohort. Our study provides estimates for prevalence and prognostic importance of different variants of aIAB, providing a support to use biphasic P-wave morphology in lead aVF as the basis for aIAB definition.

Molecular Glues: The Adhesive Connecting Targeted Protein Degradation to the Clinic.

Targeted protein degradation is a rapidly exploding drug discovery strategy that uses small molecules to recruit disease-causing proteins for rapid destruction mainly via the ubiquitin-proteasome pathway. It shows great potential for treating diseases such as cancer and infectious, inflammatory, and neurodegenerative diseases, especially for those with "undruggable" pathogenic protein targets. With the recent rise of the "molecular glue" type of protein degraders, which tighten and simplify the connection of an E3 ligase with a disease-causing protein for ubiquitination and subsequent degradation, new therapies for unmet medical needs are being designed and developed. Here we use data from the CAS Content Collection and the publication landscape of recent research on targeted protein degraders to provide insights into these molecules, with a special focus on molecular glues. We also outline the advantages of the molecular glues and summarize the advances in drug discovery practices for molecular glue degraders. We further provide a thorough review of drug candidates in targeted protein degradation through E3 ligase recruitment. Finally, we highlight the progression of molecular glues in drug discovery pipelines and their targeted diseases. Overall, our paper provides a comprehensive reference to support the future development of molecular glues in medicine.

Atrial Fibrillation and Dementia: A Report From the AF-SCREEN International Collaboration.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Can 24 h of ambulatory ECG be used to triage patients to extended monitoring?

BACKGROUND: Access to long-term ambulatory recording to detect atrial fibrillation (AF) is limited for economical and practical reasons. We aimed to determine whether 24 h ECG (24hECG) data can predict AF detection on extended cardiac monitoring. METHODS: We included all US patients from 2020, aged 17-100 years, who were monitored for 2-30 days using the PocketECG device (MEDICALgorithmics), without AF ≥30 s on the first day (n = 18,220, mean age 64.4 years, 42.4% male). The population was randomly split into equal training and testing datasets. A Lasso model was used to predict AF episodes ≥30 s occurring on days 2-30. RESULTS: The final model included maximum heart rate, number of premature atrial complexes (PACs), fastest rate during PAC couplets and triplets, fastest rate during premature ventricular couplets and number of ventricular tachycardia runs ≥4 beats, and had good discrimination (ROC statistic 0.7497, 95% CI 0.7336-0.7659) in the testing dataset. Inclusion of age and sex did not improve discrimination. A model based only on age and sex had substantially poorer discrimination, ROC statistic 0.6542 (95% CI 0.6364-0.6720). The prevalence of observed AF in the testing dataset increased by quintile of predicted risk: 0.4% in Q1, 2.7% in Q2, 6.2% in Q3, 11.4% in Q4, and 15.9% in Q5. In Q1, the negative predictive value for AF was 99.6%. CONCLUSION: By using 24hECG data, long-term monitoring for AF can safely be avoided in 20% of an unselected patient population whereas an overall risk of 9% in the remaining 80% of the population warrants repeated or extended monitoring.

Supraventricular arrhythmia, N-terminal pro-brain natriuretic peptide and troponin T concentration in relation to incidence of atrial fibrillation: a prospective cohort study.

BACKGROUND: Frequent supraventricular arrhythmia is associated with increased incidence of atrial fibrillation. However, it is unknown whether the prognostic significance of supraventricular arrhythmia is modified by plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) or troponin T (TnT). This study examined the interrelationships between NT-proBNP, TnT levels and frequent supraventricular arrhythmia, and whether these biomarkers and a measure of frequent supraventricular arrhythmia could improve risk assessment for incidence of AF. METHODS: Supraventricular extrasystoles (SVEs) and supraventricular tachycardias were assessed from 24-h electrocardiograph recordings in 373 individuals initially without AF. Elevated NT-pro-BNP, TnT and SVEs was defined as a measurement in the top quartile of the study population distribution. Incident cases of AF were retrieved by linkage with the Swedish National Patient Register. RESULTS: During a mean follow-up of 15.4 years, 88 subjects had a diagnosis of AF. After multivariable adjustment, individuals with both elevated NT-proBNP and frequent SVEs had a significantly increased incidence of AF, compared to subjects without elevated NT-proBNP or frequent SVEs (hazard ratio (HR) 4.61, 95% confidence interval (CI) 2.45-8.69), and compared to individuals with either elevated NT-proBNP or frequent SVEs (both P < 0.05). HRs for frequent SVEs alone or elevated NT-proBNP alone were 2.32 (95% CI 1.33-4.06) and 1.52 (95% CI 0.76-3.05), respectively. The addition of NT-pro-BNP and SVEs to a validated risk prediction score for AF, CHARGE-AF, resulted in improved prediction (Harrell's C 0.751 (95% CI 0.702-0.799) vs 0.720 (95% CI 0.669-0.771), P = 0.015). CONCLUSION: Subjects with both elevated NT-proBNP and frequent SVEs have substantially increased risk of AF, and the use of these variables could improve long-term prediction of incident AF.

Searching for Atrial Fibrillation Poststroke: A White Paper of the AF-SCREEN International Collaboration.

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.

ST segment depression on 24-hour electrocardiography predicts incident atrial fibrillation in two population-based cohorts.

Aims: ST-depression at 24hECG has not been studied in relation to atrial fibrillation (AF) risk. We aimed to determine whether ST-depression at 24hECG was associated with incident AF in two Swedish population-based cohorts - a sub-cohort of the Malmö Diet and Cancer study (MDCS), and the cohort 'Men born in 1914', and to determine whether 24hECG could be used to predict AF development. Methods and results: There were 378 acceptable 24hECG recordings in the MDCS (mean age 64.5 years, 43% men) and 394 acceptable recordings in 'Men born in 1914' (mean age 68.8 years). Incidence of AF was monitored using national registers of hospitalizations and outpatient visits in Sweden. Mean follow-up ± SD (cumulative incidence) was 10.4 ± 2 years (11.3%) in MDCS, and 10.9 ± 4 years (7.3%) in 'Men born in 1914'. ST-depressions were independently associated with incident AF; hazard ratio (HR) (95% CI) 2.41 (1.29-4.50, P = 0.006) and 2.28 (1.05-4.95, P = 0.038) after adjustment [age, sex, height, weight, systolic blood pressure, smoking, anti-hypertensive drugs, LDL/total cholesterol, and HOMA-IR (in MDCS)]. AF incidence was substantially lower in individuals who had neither ST-depressions or high supraventricular activity (SVA, negative predictive value 0.97 and 0.94, in MDCS and 'Men born in 1914', respectively), and similar in men and women. Conclusion: ST-depression at 24h-ECG is independently associated with incident AF, and incidence is substantially lower in individuals with neither ST-depression or high SVA. 24hECG can be used not only to diagnose AF but also to identify individuals at high and low AF risk.

Serum Potassium Is Positively Associated With Stroke and Mortality in the Large, Population-Based Malmö Preventive Project Cohort.

BACKGROUND AND PURPOSE: Low serum potassium is associated with stroke in populations with cardiovascular disease, hypertension, and diabetes mellitus but has not been studied in a mainly healthy population. We aimed to study the relation between serum potassium and incident stroke and mortality in the Malmö Preventive Project, a large cohort with screening in early mid-life and follow-up >25 years. METHODS: Serum potassium measurements and covariates were available in 21 353 individuals (79% men, mean age 44 years). Mean follow-up time was 26.9 years for stroke analyses and 29.3 years for mortality analyses. There were 2061 incident stroke events and 8709 deaths. Cox regression analyses adjusted for multiple stroke risk factors (age, sex, height, weight, systolic blood pressure, fasting blood glucose, serum sodium, current smoking, prevalent diabetes mellitus, prevalent coronary artery disease, and treatment for hypertension) were fitted. RESULTS: There was an independent, linear association between serum potassium, per mmol/L increase, and both stroke (hazard ratio, 1.33; 95% confidence interval, 1.17-1.52; P<0.0001) and mortality (hazard ratio, 1.20; 95% confidence interval, 1.13-1.28; P<0.0001). This was significant in subjects both older and younger than the median age (46.5 years), and there was evidence of an interaction with serum sodium. The association was positive and significant for both ischemic stroke and intracerebral hemorrhage and in both hypertensive and normotensive subjects. CONCLUSIONS: Serum potassium, measured in early mid-life, was linearly associated with both incidence of ischemic stroke and intracerebral hemorrhage and all-cause mortality. An interaction with serum sodium implies that factors related to electrolyte balance and incident hypertension may be mediating factors.

Reduced forced expiratory volume is associated with increased incidence of atrial fibrillation: the Malmo Preventive Project.

AIMS: Reduced forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) have been associated with increased incidence of cardiovascular diseases. However, whether reduced lung function is also a risk factor for incidence of atrial fibrillation (AF) is still unclear. We aimed to determine whether lung function predicted AF in the Malmö Preventive Project, a large population-based cohort with a long follow-up. METHODS AND RESULTS: The study population consisted of 7674 women and 21 070 men, mean age 44.6 years. The cohort was followed on average for 24.8 years, during which time 2669 patients were hospitalized due to AF. The incidence of AF in relationship to quartiles of FEV1 and FVC and per litre decrease at baseline was determined using a Cox proportional hazards model adjusted for age, height, weight, current smoking status, systolic blood pressure, erythrocyte sedimentation rate, and fasting blood glucose. Forced expiratory volume in one second was inversely related to incidence of AF (per litre reduction in FEV1) hazard ratio (HR): 1.39 [95% confidence interval (CI): 1.16-1.68; P = 0.001] for women, and HR: 1.20 (95% CI: 1.13-1.29; P < 0.0001) for men. Forced vital capacity was also inversely related to incidence of AF (per litre reduction in FVC) HR: 1.20 (95% CI: 1.03-1.41; P = 0.020) for women, and HR: 1.08 (95% CI: 1.02-1.14; P = 0.01) for men. This relationship was consistent in non-smokers as well as smokers, and among individuals younger than the median age of 45.8 years or normotensive subjects. CONCLUSION: Impaired lung function is an independent predictor of AF. This may explain some risk of AF that is currently unaccounted for.

Low fasting plasma insulin is associated atrial fibrillation in men from a cohort study--the Malmö preventive project.

BACKGROUND: Type 2 diabetes has been associated with increased incidence of atrial fibrillation (AF) and cardiovascular disease. Controversy remains regarding the role of insulin in the epidemiology of AF risk. The aim of the present study was to study the association between fasting plasma insulin (FPI) and incidence of AF, as well as any effect modification by fasting blood glucose (FBG) or 2 h post-load blood glucose and body mass index (BMI). METHODS: The study population consisted of 6052 men and 1014 women followed for an average of 26.2 years. There were 983 cases of incident AF. Analysis was performed using Cox regression and competing risks regression approaches. The population was analysed as a whole, and by subgroups according to glucose levels and BMI. RESULTS: After adjustment for age, height, weight, systolic blood pressure and smoking there was a significant inverse association between FPI and AF (hazard ratio; HR) for 4th vs. 1st quartile: 0.69 (95% confidence interval (CI): 0.57-0.83, p < 0.0001) in the cohort as a whole. Among men the corresponding values were HR 0.64 (95% CI 0.52-0.78, p < 0.001) and among women HR 1.16 (95% CI 0.69-1.93, p = 0.58); p-value for interaction 0.06. The protective effects of insulin tended to be weaker in subjects with elevated fasting glucose, implying that the relation between FPI and incident AF could be dependent on the status of individual's glucose metabolism. CONCLUSIONS: High levels of FPI are associated with lower risk of incident AF in a middle-aged population with a long follow-up.

Reference ranges for ambulatory heart rate measurements in a middle-aged population.

BACKGROUND: Elevated heart rate (HR) predicts cardiovascular disease and mortality, but there are no established normal limits for ambulatory HR. We used data from the Swedish CArdioPulmonary Imaging Study to determine reference ranges for ambulatory HR in a middle-aged population. We also studied clinical correlates of ambulatory HR. METHODS: A 24-hour ECG was registered in 5809 atrial fibrillation-free individuals, aged 50-65 years. A healthy subset (n=3942) was used to establish reference values (excluding persons with beta-blockers, cardiovascular disease, hypertension, heart failure, anaemia, diabetes, sleep apnoea or chronic obstructive pulmonary disease).Minimum HR was defined as the lowest 1-minute HR. Reference ranges are reported as means±SDs and 2.5th-97.5th percentiles. Clinical correlates of ambulatory HR were analysed with multivariable linear regression. RESULTS: The average mean and minimum HRs were 73±9 and 48±7 beats per minute (bpm) in men and 76±8 and 51±7 bpm in women; the reference range for mean ambulatory HR was 57-90 bpm in men and 61-92 bpm in women. Average daytime and night-time HRs are also reported. Clinical correlates, including age, sex, height, body mass index, physical activity, smoking, alcohol intake, diabetes, hypertension, haemoglobin level, use of beta-blockers, estimated glomerular filtration rate, per cent of predicted forced expiratory volume in 1 s and coronary artery calcium score, explained <15% of the interindividual differences in HR. CONCLUSION: Ambulatory HR varies widely in healthy middle-aged individuals, a finding with relevance for the management of patients with a perception of tachycardia. Differences in ambulatory HR between individuals are largely independent of common clinical correlates.

RETRACTED: PO-04-037 ARTIFICIAL INTELLIGENCE FOR ANALYSIS OF MOBILE CARDIAC TELEMETRY.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This abstract has been retracted at the request of the Authors; please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The abstract was withdrawn after being accepted for presentation at Heart Rhythm, the annual meeting of the Heart Rhythm Society, because there was substantial content development after it had been submitted, both in terms of more in-depth analyses and quantitative changes due to final adjudication of events. The Authors intended to withdraw the abstract from publication as well but omitted to do so. The Authors apologize for the inconvenience caused by this oversight.

Ventricular tachycardia risk prediction with an abbreviated duration mobile cardiac telemetry.

Background: Ventricular tachycardia (VT) occurs intermittently, unpredictably, and has potentially lethal consequences. Objective: Our aim was to derive a risk prediction model for VT episodes ≥10 beats detected on 30-day mobile cardiac telemetry based on the first 24 hours of the recording. Methods: We included patients who were monitored for 2 to 30 days in the United States using full-disclosure mobile cardiac telemetry, without any VT episode ≥10 beats on the first full recording day. An elastic net prediction model was derived for the outcome of VT ≥10 beats on monitoring days 2 to 30. Potential predictors included age, sex, and electrocardiographic data from the first 24 hours: heart rate; premature atrial and ventricular complexes occurring as singlets, couplets, triplets, and runs; and the fastest rate for each event. The population was randomly split into training (70%) and testing (30%) samples. Results: In a population of 19,781 patients (mean age 65.3 ± 17.1 years, 43.5% men), with a median recording time of 18.6 ± 9.6 days, 1510 patients had at least 1 VT ≥10 beats. The prediction model had good discrimination in the testing sample (area under the receiver-operating characteristic curve 0.7584, 95% confidence interval 0.7340-0.7829). A model excluding age and sex had an equally good discrimination (area under the receiver-operating characteristic curve 0.7579, 95% confidence interval 0.7332-0.7825). In the top quintile of the score, more than 1 in 5 patients had a VT ≥10 beats, while the bottom quintile had a 98.2% negative predictive value. Conclusion: Our model can predict risk of VT ≥10 beats in the near term using variables derived from 24-hour electrocardiography, and could be used to triage patients to extended monitoring.

Markers of Atrial Myopathy in the General Population: Prevalence, Predictors, and Inter-Relations.

BACKGROUND: Atrial myopathy refers to structural and functional cardiac abnormalities associated with atrial fibrillation and stroke, but appropriate diagnostic criteria are lacking. OBJECTIVES: This study aimed to assess prevalence, clinical correlates, and overlap between potential atrial myopathy markers. METHODS: The population-based SCAPIS (Swedish CArdioPulmonary bioImage Study) prospectively included 6,013 subjects without atrial fibrillation with 24-hour electrocardiograms. Resting electrocardiograms measuring P-wave indices were collected at 1 screening site (n = 1,201), and a random sample (n = 385) had echocardiographic left atrial volume index (LAVi). Atrial myopathy markers were defined as ≥500 premature atrial complexes/24 h, LAVi ≥34 mL/m2, P-wave duration >120 milliseconds, or P-wave terminal force in V1 >4,000 ms·s. Clinical correlates included age, sex, body mass index, height, smoking, physical activity, coronary artery disease, diabetes, systolic blood pressure, antihypertensive medication, and low education. RESULTS: Atrial myopathy was common; 42% of the sample with all diagnostic modalities available had ≥1 atrial myopathy marker, but only 9% had 2 and 0.3% had ≥3. Only P-wave duration and LAVi were correlated (ρ = 0.10; P = 0.04). Clinical correlates of premature atrial complexes, P-wave indices, and LAVi differed; current smoking (34% increase; P < 0.001), systolic blood pressure (4%/mm Hg increase; P = 0.01), diabetes (35% increase; P = 0.001), and coronary artery disease (71% increase; P = 0.003) were associated with premature atrial complexes, physical activity ≥2 h/wk was associated with increased LAVi (ß-coefficient = 3.1; P < 0.0001) and body mass index was associated with P-wave duration (ß-coefficient = 0.4/kg/m2; P < 0.0001). CONCLUSIONS: In the general population, indirect markers of atrial myopathy are common but only weakly correlated, and their risk factor patterns are different. More studies are needed to accurately identify individuals with atrial myopathy with diagnostic methods.

Elevated premature ventricular complex counts on 24-hour electrocardiogram predict incident atrial fibrillation and heart failure-A prospective population-based cohort study.

Background: Premature ventricular complexes (PVCs) are known to predict heart failure (HF) and premature atrial contractions (PACs) are known to predict atrial fibrillation (AF) and stroke. PVCs and PACs share pathophysiological mechanisms; however, the combined effects of PVCs and PACs on HF, AF, and stroke risk have not been studied. Objectives: To study elevated PVC counts on 24-hour electrocardiogram monitoring (24hECG) in relation to incidence of AF, HF, and stroke, and whether this effect is altered by PAC frequency. Methods: The prospective population-based Malmö Diet and Cancer study includes 24hECG registrations in 375 AF- and HF-free subjects (mean age 65 years, 55% women). During 17 years of follow-up there were 28 HF, 89 AF, and 28 stroke events. The hazard ratios (HR) of elevated PVC counts (defined as the top quartile, ≥77/24 hours) vs lower quartiles were assessed using multivariable adjusted Cox regression models. Results: Elevated PVC counts predicted incident AF (HR 1.9, 95% confidence interval [CI] 1.2-3.0) and HF (HR 3.1, 95% CI 1.4-7.0). Results were similar after adjustment for NT-proBNP and PACs. Multiform PVCs were associated with even higher risks (HR 2.8, 95% CI: 1.7-4.6 for AF; HR 5.0, 95% CI 2.2-11.7 for HF), as was the presence of both elevated PACs and PVCs (9% of the population, HR 4.1, 95% CI 2.4-6.8 for AF and HR 4.3, 95% CI 1.7-11.4 for HF). No significant association was found between elevated PVC counts and incident stroke. Conclusion: Elevated PVC counts predict incident AF and HF, particularly if PVCs are multiform or occur in combination with elevated PAC counts.

Cardiovagal Function Measured by the Deep Breathing Test: Relationships With Coronary Atherosclerosis.

Background The cardiovagal function can be assessed by quantification of respiratory sinus arrhythmia (RSA) during a deep breathing test. However, population studies of RSA and coronary atherosclerosis are lacking. This population-based study examined the relationship between RSA during deep breathing and coronary atherosclerosis, assessed by coronary artery calcium score (CACS). Methods and Results SCAPIS (Swedish Cardiopulmonary Bioimage Study) randomly invited men and women aged 50 to 64 years from the general population. CACS was obtained from computed tomography scanning, and deep breathing tests were performed in 4654 individuals. Expiration-inspiration differences (E-Is) of heart rates were calculated, and reduced RSA was defined as E-I in the lowest decile of the population. The relationship between reduced RSA and CACS (CACS≥100 or CACS≥300) was calculated using multivariable-adjusted logistic regression. The proportion of CACS≥100 was 24% in the lowest decile of E-I and 12% in individuals with E-I above the lowest decile (P<0.001), and the proportion of CACS≥300 was 12% and 4.8%, respectively (P<0.001). The adjusted odds ratio (OR) for CACS≥100 was 1.42 (95% CI, 1.10-1.84) and the adjusted OR for CACS≥300 was 1.62 (95% CI, 1.15-2.28), when comparing the lowest E-I decile with deciles 2 to 10. Adjusted ORs per 1 SD lower E-I were 1.17 (P=0.001) for CACS≥100 and 1.28 (P=0.001) for CACS≥300. Conclusions Low RSA during deep breathing is associated with increased coronary atherosclerosis as assessed by CACS, independently of traditional cardiovascular risk factors. Cardiovagal dysfunction could be a prevalent and modifiable risk factor for coronary atherosclerosis in the general population.

Cardiovascular risk factors and autonomic indices in relation to fatal and non-fatal coronary events.

OBJECTIVE: Mortality caused by coronary artery disease has markedly decreased in recent years. However, a substantial proportion of patients suffering a coronary event (CE) die within the first day, most of them out of hospital. We aimed to investigate how established cardiovascular (CV) risk factors and CV autonomic indices associate with fatal versus non-fatal CEs in the population. METHODS: 33 057 individuals (mean age; 45.6 years; 10 773 women) free of coronary artery disease at baseline were included. Baseline examination, including assessment of traditional CV risk factors and autonomic indices such as heart rate and orthostatic reaction, was performed during 1974-1992, after which the subjects were monitored for incident CV disease. The Lunn-McNeil competing risks approach with a prespecified multivariable model was used to assess differences in risks for fatal and non-fatal CEs in relation to baseline CV risk factors. RESULTS: During follow-up period of 29.7 years, 5494 subjects (6.10/1000 person-years) had first CE; 1554 of these were fatal. Age, male gender, smoking, body mass index (BMI), blood pressure, pulse pressure and resting heart rate had stronger relationships with fatal CE than with non-fatal events. The effects of diabetes, serum cholesterol, antihypertensive treatment and orthostatic blood pressure responses were similar for fatal and non-fatal CE. CONCLUSIONS: Several cardiovascular risk factors, such as smoking, high BMI, blood pressure and high resting heart rate, were preferentially associated with fatal compared with non-fatal CEs. These observations may require special attention in the overall efforts to further reduce coronary artery disease mortality.

Incidence and Predictors of Heart Failure in Patients With Atrial Fibrillation.

BACKGROUND: Heart failure (HF) is a frequent cause of hospitalization and death in patients with atrial fibrillation (AF). Identifying AF patients at risk of HF hospitalization could help select individuals for intensive follow-up and treatment. METHODS: We pooled data from 3 randomized trials (ACTIVE-A, RE-LY, AVERROES) of AF patients, for derivation and internal validation of a risk score for first HF hospitalization. Secondary endpoints were cardiovascular death and a composite of HF hospitalizations and cardiovascular death. RESULTS: In 23,503 patients, the mean age was 71.3 years, and 62% were male. Over a mean follow-up of 2.0 years, 875 patients (3.7%) experienced their first HF hospitalization, and 1037 patients (4.4%) died from cardiovascular causes. Incidence rates per 100 patient-years were 1.85 for HF hospitalizations, 2.15 for cardiovascular death, and 3.71 for the composite. Independent predictors for HF hospitalizations included the following: increased age, weight, heart rate and serum creatinine level, lower height and systolic blood pressure, diabetes, vascular disease, valvular disease, heart rhythm, left ventricular hypertrophy, and intraventricular conduction delay. The C-statistic (95% confidence intervals by bootstrap simulations) was 0.717 (0.705-0.732). At 2 years of follow-up, the incidence rate of the primary outcome increased across risk-score quintiles: 0.49, 0.87, 1.29, 2.44, and 4.51 per 100 patient-years, respectively. Patients in the highest quintile had an absolute risk of 6.8% for the primary endpoint at 2 years. CONCLUSIONS: In a large AF population, new-onset HF was common. A combination of characteristics can identify high-risk patients for whom strategies to prevent HF should be considered.

INTRODUCTION: L'insuffisance cardiaque (IC) est une cause fréquente d'hospitalisation et de décès chez les patients atteints de fibrillation auriculaire (FA). Le repérage des patients atteints de FA exposés au risque d'hospitalisation liée à l'IC pourrait faciliter la sélection des individus pour un suivi et un traitement intensifs. MÉTHODES: Nous avons regroupé les données de trois essais contrôlés (ACTIVE-A, RE-LY, AVERROES) de patients atteints de FA pour obtenir la dérivation et la validation interne d'un score de risque lors de la première hospitalisation liée à l'IC. Les critères secondaires étaient les décès dus aux maladies cardiovasculaires et le critère composite d'hospitalisations liées à l'IC et de décès dus aux maladies cardiovasculaires. RÉSULTATS: L'âge moyen des 23 503 patients, dont 62 % étaient des hommes, était de 71,3 ans. Durant un suivi moyen de 2,0 ans, 875 patients (3,7 %) ont subi leur première hospitalisation liée à l'IC, et 1 037 patients (4,4 %) sont morts de maladies cardiovasculaires. Les taux d'incidence par 100 patients-années étaient de 1,85 pour les hospitalisations liées à l'IC, de 2,15 pour les décès dus aux maladies cardiovasculaires et de 3,71 pour le critère composite. Les prédicteurs indépendants des hospitalisations liées à l'IC étaient les suivants : l'âge avancé, le poids, la fréquence cardiaque et la concentration sérique de la créatinine, la taille inférieure et la pression artérielle systolique, le diabète, les maladies vasculaires, la valvulopathie, le rythme cardiaque, l'hypertrophie ventriculaire gauche et le retard de conduction intraventriculaire. La statistique C (intervalles de confiance à 95 % obtenus par simulations d'auto-amorçage) était de 0,717 (0,705-0,732). Après deux ans de suivi, le taux d'incidence du critère d'évaluation principal augmentait de façon respective dans tous les quintiles de scores de risque : 0,49, 0,87, 1,29, 2,44 et 4,51 par 100 patients-années. Les patients dans le quintile supérieur avaient un risque absolu du critère d'évaluation principal de 6,8 % après deux ans. CONCLUSIONS: Dans une vaste population atteinte de FA, l'IC d'apparition récente était fréquente. La combinaison des caractéristiques peut permettre de déterminer les patients exposés à un risque élevé chez lesquels des stratégies de prévention de l'IC devraient être envisagées.