Autonomous Chest Radiograph Reporting Using AI: Estimation of Clinical Impact.

Background Automated interpretation of normal chest radiographs could alleviate the workload of radiologists. However, the performance of such an artificial intelligence (AI) tool compared with clinical radiology reports has not been established. Purpose To perform an external evaluation of a commercially available AI tool for (a) the number of chest radiographs autonomously reported, (b) the sensitivity for AI detection of abnormal chest radiographs, and (c) the performance of AI compared with that of the clinical radiology reports. Materials and Methods In this retrospective study, consecutive posteroanterior chest radiographs from adult patients in four hospitals in the capital region of Denmark were obtained in January 2020, including images from emergency department patients, in-hospital patients, and outpatients. Three thoracic radiologists labeled chest radiographs in a reference standard based on chest radiograph findings into the following categories: critical, other remarkable, unremarkable, or normal (no abnormalities). AI classified chest radiographs as high confidence normal (normal) or not high confidence normal (abnormal). Results A total of 1529 patients were included for analysis (median age, 69 years [IQR, 55-69 years]; 776 women), with 1100 (72%) classified by the reference standard as having abnormal radiographs, 617 (40%) as having critical abnormal radiographs, and 429 (28%) as having normal radiographs. For comparison, clinical radiology reports were classified based on the text and insufficient reports excluded (n = 22). The sensitivity of AI was 99.1% (95% CI: 98.3, 99.6; 1090 of 1100 patients) for abnormal radiographs and 99.8% (95% CI: 99.1, 99.9; 616 of 617 patients) for critical radiographs. Corresponding sensitivities for radiologist reports were 72.3% (95% CI: 69.5, 74.9; 779 of 1078 patients) and 93.5% (95% CI: 91.2, 95.3; 558 of 597 patients), respectively. Specificity of AI, and hence the potential autonomous reporting rate, was 28.0% of all normal posteroanterior chest radiographs (95% CI: 23.8, 32.5; 120 of 429 patients), or 7.8% (120 of 1529 patients) of all posteroanterior chest radiographs. Conclusion Of all normal posteroanterior chest radiographs, 28% were autonomously reported by AI with a sensitivity for any abnormalities higher than 99%. This corresponded to 7.8% of the entire posteroanterior chest radiograph production. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Park in this issue.

Commercially Available Chest Radiograph AI Tools for Detecting Airspace Disease, Pneumothorax, and Pleural Effusion.

Background Commercially available artificial intelligence (AI) tools can assist radiologists in interpreting chest radiographs, but their real-life diagnostic accuracy remains unclear. Purpose To evaluate the diagnostic accuracy of four commercially available AI tools for detection of airspace disease, pneumothorax, and pleural effusion on chest radiographs. Materials and Methods This retrospective study included consecutive adult patients who underwent chest radiography at one of four Danish hospitals in January 2020. Two thoracic radiologists (or three, in cases of disagreement) who had access to all previous and future imaging labeled chest radiographs independently for the reference standard. Area under the receiver operating characteristic curve, sensitivity, and specificity were calculated. Sensitivity and specificity were additionally stratified according to the severity of findings, number of findings on chest radiographs, and radiographic projection. The χ2 and McNemar tests were used for comparisons. Results The data set comprised 2040 patients (median age, 72 years [IQR, 58-81 years]; 1033 female), of whom 669 (32.8%) had target findings. The AI tools demonstrated areas under the receiver operating characteristic curve ranging 0.83-0.88 for airspace disease, 0.89-0.97 for pneumothorax, and 0.94-0.97 for pleural effusion. Sensitivities ranged 72%-91% for airspace disease, 63%-90% for pneumothorax, and 62%-95% for pleural effusion. Negative predictive values ranged 92%-100% for all target findings. In airspace disease, pneumothorax, and pleural effusion, specificity was high for chest radiographs with normal or single findings (range, 85%-96%, 99%-100%, and 95%-100%, respectively) and markedly lower for chest radiographs with four or more findings (range, 27%-69%, 96%-99%, 65%-92%, respectively) (P < .001). AI sensitivity was lower for vague airspace disease (range, 33%-61%) and small pneumothorax or pleural effusion (range, 9%-94%) compared with larger findings (range, 81%-100%; P value range, > .99 to < .001). Conclusion Current-generation AI tools showed moderate to high sensitivity for detecting airspace disease, pneumothorax, and pleural effusion on chest radiographs. However, they produced more false-positive findings than radiology reports, and their performance decreased for smaller-sized target findings and when multiple findings were present. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Yanagawa and Tomiyama in this issue.

Wireless Single-Lead ECG Monitoring to Detect New-Onset Postoperative Atrial Fibrillation in Patients After Major Noncardiac Surgery: A Prospective Observational Study.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is associated with several cardiovascular complications and higher mortality. Several pathophysiological processes such as hypoxia can trigger POAF, but these are sparsely elucidated, and POAF is often asymptomatic. In patients undergoing major gastrointestinal cancer surgery, we aimed to describe the frequency of POAF as automatically estimated and detected via wireless repeated sampling monitoring and secondarily to describe the association between preceding vital sign deviations and POAF. METHOD: Patients ≥60 years of age undergoing major gastrointestinal cancer surgery were continuously monitored for up to 4 days postoperatively. Electrocardiograms were obtained every minute throughout the monitoring period. Clinical staff were blinded to all measurements. As for the primary outcome, POAF was defined as 30 consecutive minutes or more detected by a purpose-built computerized algorithm and validated by cardiologists. The primary exposure variable was any episode of peripheral oxygen saturation (Spo2) <85% for >5 consecutive minutes before POAF. RESULTS: A total of 30,145 hours of monitoring was performed in 398 patients, with a median of 92 hours per patient (interquartile range [IQR], 54-96). POAF was detected in 26 patients (6.5%; 95% confidence interval [CI], 4.5-9.4) compared with 14 (3.5%; 95% CI, 1.94-5.83) discovered by clinical staff in the monitoring period. POAF was followed by 9.4 days hospitalization (IQR, 6.5-16) versus 6.5 days (IQR, 2.5-11) in patients without POAF. Preceding episodes of Spo2 <85% for >5 minutes (OR, 1.02; 95% CI, 0.24-4.00; P = .98) or other vital sign deviations were not significantly associated with POAF. CONCLUSIONS: New-onset POAF occurred in 6.5% (95% CI, 4.5-9.4) of patients after major gastrointestinal cancer surgery, and 1 in 3 cases was not detected by the clinical staff (35%; 95% CI, 17-56). POAF was not preceded by vital sign deviations.

Vasodilators for acute heart failure-A protocol for a systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis.

BACKGROUND: Above one million annual hospitalizations occur with a primary diagnosis of acute heart failure in the US, with comparable numbers in Europe. Within 1 year, over a third of patients have died or been re-hospitalized. Most patients have acutely elevated systemic and/or intra-cardiac blood pressures as part of the acute heart failure syndrome. Most clinical trials of acute heart failure have aimed at reducing preload and/or afterload through drug-induced vasodilation. However, recent European guidelines downgraded the treatment recommendation of vasodilators. We aim to assess the beneficial and harmful effects of vasodilators in the treatment of acute heart failure. METHODS: This protocol for a systematic review was undertaken using the recommendations of The Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We plan to include all randomized clinical trials assessing the use of vasodilators in the treatment of AHF. The systematic review will be conducted based on a systematic search of relevant major medical databases without date restrictions, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in addition to clinical trial registries. We will begin the searches in August 2022. All included trials will be assessed and classified at low risk of bias or at high risk of bias. Our conclusions will be based on the results from the primary outcomes with concomitant low risk of bias. Extracted data will be analyzed using Trial Sequential Analysis 0.9.5.10, Review Manager 5.3, and SAS. We will assess the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation. We will register this systematic review at Prospero and aim to update it when new trials are published. DISCUSSION: This protocol defines the detailed methodology and approach used for a systematic review on whether vasodilation for acute heart failure improves patient outcome. This systematic review will potentially aid clinicians in deciding the optimal treatment of patients admitted with acute heart failure. Furthermore, this review will explore gaps in our knowledge and thus guide future research within acute heart failure.

Effects of liraglutide on diastolic function parameters in patients with type 2 diabetes and coronary artery disease: a randomized crossover study.

BACKGROUND: Diastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD). The GLP-1 receptor agonist, liraglutide, has shown to induce weight loss and improve metabolic factors, thus modulating factors associated with diastolic dysfunction. We have previously reported the effects of liraglutide on systolic function, and in this current study we explore the effects of liraglutide on diastolic function parameters in patients with stable CAD, preserved left ventricular ejection fraction (LVEF), and newly diagnosed T2DM. METHODS: Thirty subjects were randomized to liraglutide or placebo intervention for 12 + 12-weeks in this double-blind cross-over study. 2D-echocardiography using tissue velocity imaging was used for assessment of diastolic function parameters. Early diastolic filling velocity (E), late atrial filling velocity (A), E-wave deceleration time (EDT) and E/A ratio was assessed from the pulse wave (PW)-Doppler velocity recording of the mitral inflow. Peak early diastolic annular velocities (e') was measured from color tissue doppler images. RESULTS: Liraglutide, when compared to placebo, induced a significant reduction in average e' and lateral e' velocities (- 0.57 cm/s [- 1.05 to - 0.08] and -0.74 cm/s [-1.32 to -0.15], respectively). Adjusted for the concomitant increase in HR (+ 6.16 bpm [0.79 to 11.54], the changes were not significant. No significant changes in other diastolic function parameters were observed. CONCLUSIONS: Liraglutide therapy did not improve any diastolic function parameters in subjects with T2DM, CAD, and preserved LVEF. Instead, a deterioration in e' was observed, which was associated to an increase in heart rate induced by liraglutide therapy. Trial registration Clinical Trial Registration: http://www.clinicaltrials.gov (unique identifier: NCT01595789) (first submitted May 8, 2012).

Night-time heart rate variability identifies high-risk people among people with uncomplicated type 2 diabetes mellitus.

BACKGROUND: Low heart rate variability (HRV) reflects cardiac autonomic neuropathy, which is associated with increased cardiovascular mortality in people with type 2 diabetes mellitus (T2DM). Measuring HRV is challenged by environmental noise, mental stress and physical activity during daytime. Night-time HRV during sleep may be a more valid tool to measure cardiac autonomic neuropathy and therefore may improve prediction of cardiovascular (CV) events in low-risk people with T2DM. METHODS: Copenhagen Holter Study included 678 community-dwelling participants aged 55-75 years who were free of previous CV disease. Day and night-time HRV were available for 653 participants. The population included 133 people with well-controlled T2DM and newly recognized T2DM (mean HbA1c 55 mmol/mol [7.2%]). HRV is defined as standard deviation for the mean value of normal-to-normal complexes (SDNN). Night-time HRV measurements were pre-defined from 2:00 to 2:15 AM. Cardiovascular events were defined as CV death, myocardial infarction, stroke or coronary revascularization. RESULTS: Median follow-up time was 14.4 years. During this period, 245 death and 149 CV events (CV death 36, myocardial infarction 42, revascularisation procedures 46, stroke 70) occurred in total. Among people with T2DM, 41 CV events were observed (CV death 13, myocardial infarction 13, revascularisation procedures 17, stroke 18). Night-time SDNN was inversely associated with CV events in people with T2DM, (hazard ratio [HR]: 0.74 95% confidence interval [CI]:0.61-0.89) for each 10-millisecond increment in SDNN after adjustment for the conventional risk factors sex, age, LDL cholesterol, smoking, systolic blood pressure and by also including glucose CRP and NT-proBNP in adjustment. Twenty-four-hour HRV was not associated with CV events, but associated with all-cause mortality in people with T2DM. Conventional risk factors had a receiver operating characteristic (ROC) value of 0.704 (95% CI 0.602-0.806) to predict CV events in people with T2DM. The prediction of CV events by conventional risk factors was improved in people with T2DM by the addition of night-time SDNN; ROC 0.765 (95% CI 0.669-0.862), p = 0.037, but ROC was not improved by addition of CRP and NT-proBNP in the model. In people with T2DM and night-time SDNN ≤30 ms, the 10-year risk of CV death and CV event rate was 12% and 45%, respectively, which re-allocated them to a 'very high-risk' group according to current guidelines. CONCLUSION: Reduced night-time HRV predicts increased risk of CV events in people with well-controlled T2DM, thus night-time HRV may add to traditional risk factors in predicting CV events in people with T2DM.

Increased risk of sudden death in untreated primary carnitine deficiency.

Primary carnitine deficiency (PCD) affects fatty acid oxidation and is associated with cardiomyopathy and cardiac arrhythmia, but the risk of sudden death in PCD is unknown. The Faroe Islands have a high prevalence of PCD, 1:300. This study systematically investigated a possible association between untreated PCD and sudden death in young Faroese subjects. We investigated all medico-legal cases of sudden death between 1979 and 2012 among subjects below the age of 45. Stored biomaterial was examined with molecular genetic analysis to reveal PCD. We compared the prevalence of PCD among sudden death cases with that of the background population (0.23%) to calculate the odds ratio (OR) for sudden death with PCD. Biomaterial was available and genetically analyzed from 53 of 65 sudden death cases (82%) in the Faroe Islands. Six (one male and five females) of the 53 cases were homozygous for the PCD related c.95A>G mutation-a prevalence of 11.3% (95% CI 5%-23%) and an OR of 54.3 (95% CI 21-138, P < .0001) for the association between sudden death and untreated PCD. Only 11 of the 53 sudden death cases were women-of whom five were homozygous for the c.95A>G mutation (45.5%) yielding an OR of 348.8 (95% CI 94-1287, P < .0001) for the association between sudden death and untreated PCD in females. This study showed a strong association between sudden death and untreated PCD, especially in females.

Effect of liraglutide on estimates of lipolysis and lipid oxidation in obese patients with stable coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial.

Elevated levels of non-esterified fatty acids (NEFA) play a role in insulin resistance, impaired beta-cell function and they are a denominator of the abnormal atherogenic lipid profile that characterizes obese patients with type 2 diabetes (T2DM). We hypothesized that the GLP-1 receptor agonist liraglutide, in combination with metformin, would reduce lipolysis. In a randomized, double-blind, placebo-controlled, cross-over trial, 41 T2DM patients with coronary artery disease were randomized and treated with liraglutide-metformin vs placebo-metformin during 12- + 12-week periods with a wash-out period of at least 2 weeks before and between the intervention periods. NEFA kinetics were estimated using the Boston Minimal Model of NEFA metabolism, with plasma NEFA and glucose levels measured during a standard 180-minute frequently sampled intravenous glucose tolerance test. Liraglutide-metformin reduced estimates of lipolysis. Furthermore, placebo-metformin increased estimates of lipid oxidation, while treatment with liraglutide eliminated this effect. We conclude that liraglutide exerts a clinically relevant reduction in estimates of lipolysis and lipid oxidation which is explained, in part, by improved insulin secretion, as revealed by an intravenous glucose tolerance test.

Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve Stenosis: The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS).

BACKGROUND: Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis is scarce. We used data from the SEAS trial (Simvastatin Ezetimibe in Aortic Stenosis) to assess what blood pressure (BP) would be optimal. METHODS: A total of 1767 patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease were analyzed. Outcomes were all-cause mortality, cardiovascular death, heart failure, stroke, myocardial infarction, and aortic valve replacement. BP was analyzed in Cox models as the cumulative average of serially measured BP and a time-varying covariate. RESULTS: The incidence of all-cause mortality was highest for average follow-up systolic BP ≥160 mm Hg (4.3 per 100 person-years; 95% confidence interval [CI], 3.1-6.0) and lowest for average systolic BP of 120 to 139 mm Hg (2.0 per 100 person-years; 95% CI, 1.6-2.6). In multivariable analysis, all-cause mortality was associated with average systolic BP <120 mm Hg (hazard ratio [HR], 3.4; 95% CI, 1.9-6.1), diastolic BP ≥90 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), and pulse pressure <50 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), with systolic BP of 120 to 139 mm Hg, diastolic BP of 70 to 79 mm Hg, and pulse pressure of 60 to 69 mm Hg taken as reference. Low systolic and diastolic BPs increased risk in patients with moderate aortic stenosis. With a time-varying systolic BP from 130 to 139 mm Hg used as reference, mortality was increased for systolic BP ≥160 mm Hg (HR, 1.7; P=0.033) and BP of 120 to 129 mm Hg (HR, 1.6; P=0.039). CONCLUSIONS: Optimal BP seems to be systolic BP of 130 to 139 mm Hg and diastolic BP of 70 to 90 mm Hg in these patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease or diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes.

AIMS: The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). METHODS: The design of the study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM. Patients were treated with liraglutide/metformin vs placebo/metformin for a 12 + 12-week period with ≥2-week wash-out. First phase insulin secretion (AIRg), Si and Sg were estimated by the Bergman Minimal Model, enabling calculation of beta-cell function; Disposition Index (DI) = AIRg × Si. A total of 30 patients from among 41 randomized were available for paired analysis. RESULTS: Baseline characteristics were: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m2 (SD 4.8), fasting plasma-glucose 6.9 mmol/L (IQR 6.1; 7.4) and HOMA-IR 4.9 (IQR 3.0; 7.5). Liraglutide treatment improved AIRg by 3-fold, 497 mU × L-1 × min (IQR 342; 626, P < .0001) and DI by 1-fold, 766 (SD 824, P < .0001). Despite a significant weight loss of -2.7 kg (-6.7; -0.6) during liraglutide treatment, we found no improvement in HOMA-IR, Si or Sg. Weight loss during liraglutide therapy did not result in a carry-over effect. CONCLUSION: Liraglutide as add-on to metformin induces a clinically significant improvement in beta-cell function in overweight/obese, high cardiovascular risk patients with newly diagnosed well-controlled T2DM and CAD. The effect of liraglutide on DI is mediated entirely by improved AIRg whereas the effects on Si and Sg are neutral.

Atrial ectopy and N-terminal pro-B-type natriuretic peptide as predictors of atrial fibrillation: a population-based cohort study.

AIMS: The risk of incident atrial fibrillation (AF) can be estimated by clinical parameters in the Framingham AF risk model. Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and increased rate of premature atrial contractions (PACs) have been shown to be associated with AF, but the additive value of both of these biomarkers in the Framingham AF risk model has not been fully examined. METHODS AND RESULTS: A total of 646 subjects from the Copenhagen Holter Study (mean age 64.4 ± 6.8 years, 41.6% women) with no history of prior AF, stroke or cardiovascular disease were followed for the diagnosis of incident AF or death (median follow-up time 14.4 years). Median NT-proBNP was 6.7 pmol/L (IQR: 3.6-13.5), median PAC count was 1.4 beats/h (IQR: 0.6-4.5), 71 (11.0%) subjects developed AF, and 244 (37.8%) died. Multiple Cox regression including Framingham AF risk score, log-transformed NT-proBNP, and log-transformed PAC showed a significant increase in AF hazard risk [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.14-1.85, P = 0.002; HR 1.23, 95% CI 1.09-1.39, P = 0.001]. The addition of PAC to the Framingham AF risk model significantly improved the time-dependent area under the receiver operating characteristic curve (AUC 65.6 vs. 72.6; P = 0.008), while the addition of NT-proBNP did not. CONCLUSION: Atrial fibrillation risk discrimination was significantly improved by the addition of PAC to the Framingham AF risk model, but not by the addition of NT-proBNP.

Evaluation of Commercial Self-Monitoring Devices for Clinical Purposes: Results from the Future Patient Trial, Phase I.

Commercial self-monitoring devices are becoming increasingly popular, and over the last decade, the use of self-monitoring technology has spread widely in both consumer and medical markets. The purpose of this study was to evaluate five commercially available self-monitoring devices for further testing in clinical applications. Four activity trackers and one sleep tracker were evaluated based on step count validity and heart rate validity. METHODS: The study enrolled 22 healthy volunteers in a walking test. Volunteers walked a 100 m track at 2 km/h and 3.5 km/h. Steps were measured by four activity trackers and compared to gyroscope readings. Two trackers were also tested on nine subjects by comparing pulse readings to Holter monitoring. RESULTS: The lowest average systematic error in the walking tests was -0.2%, recorded on the Garmin Vivofit 2 at 3.5 km/h; the highest error was the Fitbit Charge HR at 2 km/h with an error margin of 26.8%. Comparisons of pulse measurements from the Fitbit Charge HR revealed a margin error of -3.42% ± 7.99% compared to the electrocardiogram. The Beddit sleep tracker measured a systematic error of -3.27% ± 4.60%. CONCLUSION: The measured results revealed the current functionality and limitations of the five self-tracking devices, and point towards a need for future research in this area.

Effects of the glucagon-like peptide-1 receptor agonist liraglutide on systolic function in patients with coronary artery disease and type 2 diabetes: a randomized double-blind placebo-controlled crossover study.

BACKGROUND: Patients with type 2 diabetes (T2D) and coronary artery disease (CAD) have increased risk of cardiac dysfunction. The diabetic heart is characterized by increased fatty acid oxidation and reduced glucose uptake resulting in reduced cardiac efficiency. Glucagon-like peptide-1 (GLP-1) has shown to increase myocardial glucose uptake and to improve myocardial function. We examined the effect of the GLP-1 receptor agonist, liraglutide, on the systolic function of the left ventricle (LV) in patients with T2D and stable CAD. METHODS: In this placebo-controlled crossover study, 41 subjects with T2D and stable CAD were randomized to liraglutide or placebo and underwent dobutamine stress echocardiography (DSE) and exercise tolerance test at beginning and end of each intervention. The primary endpoint was changes in LV ejection fraction. Secondary endpoints were exercise capacity and other measures of systolic function: wall motion score index (WMSI), global longitudinal strain (GLS) and strain rate (GLSR). RESULTS: Liraglutide, when compared to placebo, did not improve LV ejection fraction at rest (+0.54 %; 95 % CI 2.38-3.45), at low stress (+0.03 %; 95 % CI 3.25-3.32), at peak stress (+1.12 %; 95 % CI 3.45-5.69), or at recovery (+4.06 %; 95 % CI 0.81-8.93). No significant changes in WMSI were observed at any stress levels. GLS and GLSR at rest did not improve. The maximal exercise capacity estimated by metabolic equivalents was not affected by liraglutide. CONCLUSION: In conclusion, liraglutide did not improve the systolic function of the left ventricle during DSE or the exercise capacity in patients with T2D and stable CAD. Clinical Trial Registration http://www.clinicaltrials.gov (unique identifier: NCT01595789).

The circadian variation of premature atrial contractions.

AIMS: The aim of the study was to assess a possible circadian variation of premature atrial contractions (PACs) in a community-based population and to determine if the daily variation could be used to assess a more vulnerable period of PACs in predicting later incidence of atrial fibrillation (AF). METHODS AND RESULTS: We studied 638 subjects between the ages of 55 and 75 years from the Copenhagen Holter Study who underwent up to 48 h electrocardiogram recording. Follow-up on cardiovascular endpoints was performed in 2013 with a median follow-up time of 14.4 years. According to previous studies, two subgroups were studied based on a cut-off point of ≥720 PACs/day termed frequent PACs (n = 66) and not frequent PACs with <720 PACs/day (n = 572). Based on median values, a circadian rhythm could not be demonstrated in the population as a whole and the group without frequent PACs. However, a circadian variation was observed in the group with frequent PACs, who had the fewest PACs/h during the night with a nadir at 6 am and then reaching a peak value in the afternoon at 3 pm. Runs of PACs in all subjects showed a similar circadian variation. Both PACs/h and runs of PACs seemed to follow the daily variation in heart rate. After adjusting for relevant risk factors, the risk of AF was equal in all time intervals throughout the day. CONCLUSION: Premature atrial contractions showed a circadian variation in subjects with frequent PACs. No specific time interval of the day was more predictive of AF than others.

Increased hsCRP is associated with higher risk of aortic valve replacement in patients with aortic stenosis.

Objective To investigate relations between inflammation and aortic valve stenosis (AS) by measuring high-sensitivity C-reactive protein, at baseline (hsCRP0) and after 1 year (hsCRP1) and exploring associations with aortic valve replacement (AVR). Design We examined 1423 patients from the Simvastatin and Ezetimibe in Aortic Stenosis study. Results During first year of treatment, hsCRP was reduced both in patients later receiving AVR (2.3 [0.9-4.9] to 1.8 [0.8-5.4] mg/l, p < 0.001) and not receiving AVR (1.90 [0.90-4.10] to 1.3 [0.6-2.9] mg/l, p < 0.001). In Cox-regression analyses, hsCRP1 predicted later AVR (HR = 1.17, p < 0.001) independently of hsCRP0 (HR = 0.96, p = 0.33), aortic valve area (AVA) and other risk factors. A higher rate of AVR was observed in the group with high hsCRP0 and an increase during the first year (AVRhighCRP0CRP1inc = 47.3% versus AVRhighCRP0CRP1dec = 27.5%, p < 0.01). The prognostic benefit of a 1-year reduction in hsCRP was larger in patients with high versus low hsCRP0 eliminating the difference in incidence of AVR between high versus low hsCRP0 (AVRhighCRP0CRP1dec = 27.5% versus AVRlowCRP0CRP1dec = 25.8%, p = 0.66) in patients with reduced hsCRP during the first year. Conclusions High hsCRP1 or an increase in hsCRP during the first year of follow-up predicted later AVR independently of AVA, age, gender and other risk factors, although no significant improvement in C-statistics was observed.

Troponin T and N-terminal pro B-Type natriuretic peptide and presence of coronary artery disease.

BACKGROUND: We tested the effects of exercise intensity, sampling intervals, degree of coronary artery stenosis, and demographic factors on circulating N-terminal pro B-Type natriuretic peptide (NT-pro-BNP) and cardiac Troponin T (cTnT) in subjects suspected of coronary artery disease (CAD). MATERIALS AND METHODS: A total of 242 subjects referred for diagnostic evaluation of possible CAD had blood samples obtained before, 5 min after, and again 20 h after a symptom-limited exercise test. RESULTS: Totally 40 subjects had CAD with ≥ 50% stenosis, 115 subjects had no stenosis and 87 subjects served as controls. In univariate analysis CAD-subjects had higher median baseline NT-pro-BNP-levels (85.3 ng/L) compared with non-CAD-subjects (41.3 ng/L) and controls (40.1 ng/L), both p < 0.001, but the association disappeared in multivariate analysis adjusted for age and gender. NT-pro-BNP increased similarly after exercise in CAD-subjects, non-CAD-subjects, and controls (median increase 8.14 ng/L) and the increase was positively associated with baseline NT-pro-BNP but not presence of CAD. Median baseline cTnT was 6.25 ng/L in CAD-subjects and 3.00 ng/L in non-CAD-subjects as well as controls, both p < 0.0001. Median ΔcTnT (baseline to 20 h after exercise) was higher in CAD-subjects than non-CAD-subjects and controls (0.62 ng/L vs. 0.0 ng/L, p < 0.001). A linear relationship between ΔcTnT and 'percent of predicted maximal heart rate achieved' was found in subjects with ≥ 70% stenosis (n = 24, r = 0.4067 p = 0.046). CONCLUSIONS: Baseline cTnT and ΔcTnT were found to be independently associated with CAD and also with exercise intensity in stable chest pain subjects. These properties were not identified for NT-pro-BNP.

Risk stratification in emergency patients by copeptin.

BACKGROUND: Rapid risk stratification is a core task in emergency medicine. Identifying patients at high and low risk shortly after admission could help clinical decision-making regarding treatment, level of observation, allocation of resources and post discharge follow-up. The purpose of the present study was to determine short-, mid- and long-term mortality by plasma measurement of copeptin in unselected admitted patients. METHOD: Consecutive patients >40-years-old admitted to an inner-city hospital were included. Within the first 24 hours after admission, a structured medical interview was conducted and self-reported medical history was recorded. All patients underwent a clinical examination, an echocardiographic evaluation and collection of blood for later measurement of risk markers. RESULTS: Plasma for copeptin measurement was available from 1,320 patients (average age 70.5 years, 59.4% women). Median follow-up time was 11.5 years (range 11.0 to 12.0 years). Copeptin was elevated (that is, above the 97.5 percentile in healthy individuals).Mortality within the first week was 2.7% (17/627) for patients with elevated copeptin (above the 97.5 percentile, that is, >11.3 pmol/L) compared to 0.1% (1/693) for patients with normal copeptin concentrations (that is, ≤11.3 pmol/L) (P <0.01). Three-month mortality was 14.5% (91/627) for patients with elevated copeptin compared to 3.2% (22/693) for patients with normal copeptin. Similar figures for one-year mortality and for the entire observation period were 27.6% (173/627) versus 8.7% (60/693) and 82.9% (520/527) versus 57.5% (398/693) (P <0.01 for both), respectively.Using multivariable Cox regression analyses shows that elevated copeptin was significantly and independently related to short-, mid- and long-term mortality. Adjusted hazard ratios were 2.4 for three-month mortality, 1.9 for one-year mortality and 1.4 for mortality in the entire observation period. CONCLUSIONS: In patients admitted to an inner-city hospital, copeptin was strongly associated with short-, mid- and long-term mortality. The results suggest that rapid copeptin measurement could be a useful tool for both disposition in an emergency department and for mid- and long-term risk assessment.

Primary Carnitine deficiency in the Faroe Islands: health and cardiac status in 76 adult patients diagnosed by screening.

BACKGROUND: Carnitine deficiency can cause cardiomyopathy and cardiac arrhythmia. The prevalence in the Faroe Islands is the highest reported in the world (1:300). A nationwide screening program identified 76 Faroese adult patients (15-80 years) with Primary Carnitine Deficiency (PCD). We describe prior and current health status and symptoms in these patients, especially focusing on cardiac characteristics. METHODS: Upon identification, patients were immediately admitted for physical examination, ECG, blood tests and initiation of L-carnitine supplementation. Medical records were reviewed and patients were interviewed. Echocardiography and blood tests were performed in 35 patients before and after L-carnitine supplementation. RESULTS: All patients were either asymptomatic or had minor symptoms when diagnosed. Echocardiography including LVEF, global longitudinal strain and dimensions were normal apart from left ventricular hypertrophy with normal systolic function in one young male. Symptoms, e.g. fatigue, were reported in 43 % with a reduction to 12 % (p < 0.01) following initiation of L-carnitine supplementation. Eighty two % reported participation in sports of which 52 % were on a competitive level. ECGs showed limited changes and blood tests were normal. Mean plasma free carnitine increased from 6.1 µmol/L to 15.1 µmol/L (p < 0.01) within 50 days of L-carnitine supplementation. CONCLUSION: PCD in adults can cause serious symptoms, but adult Faroese patients identified through a screening program were predominantly asymptomatic with a normal cardiac structure and function.

Carnitine levels in 26,462 individuals from the nationwide screening program for primary carnitine deficiency in the Faroe Islands.

BACKGROUND: Primary carnitine deficiency (PCD) is an autosomal recessive disorder of fatty acid oxidation and has been associated to episodes of sudden death in the Faroe Islands. Data are presented from the nationwide population based Faroese screening program to find people with low carnitine levels indicating PCD. METHODS: Whole blood samples from dried blood spots were analysed by tandem mass spectrometry with and without butylation. Genetic analyses were performed in all people with non-butylated free carnitine (fC0) below 7 µmol/L. RESULTS: 55 % (n = 26,462) of the entire population was screened and 89 PCD patients were identified, yielding an overall prevalence of 1:297 of PCD in the Faroe Islands. Carnitine levels were positively correlated to age in both males and females (p < 0.003) although levels decreased in females when reaching fertile age. The gender difference in mean carnitine levels was significant during female fertile age (4.71 µmol/L fC0 in the age group 25-30 years, p < 0.01). A lower cut-off of 5 µmol/L in fC0 identified all homozygous for the severe genotype c.95A > G (p.N32S) (n = 20). CONCLUSION: Carnitine levels differ by gender and age. A lower cut-off of 5 µmol/L in fC0 was appropriate to identify c.95A > G homozygotes. The prevalence of PCD in the Faroe Islands is the highest reported in the world (1:297).

The acute effects of furosemide in acute heart failure assessed by remote dielectric sensing. A protocol.

INTRODUCTION: Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute heart failure (AHF). While the diuretic effect of loop diuretics is well established, it remains unclear how furosemide influences pulmonary congestion and cardiac filling pressures in the hyperacute phase before significant diuresis occurs. METHODS: This was a prospective study of adult patients with AHF and objective signs of pulmonary congestion admitted to the cardiac ward. Remote dielectric sensing (ReDS) will directly measure lung fluid content, and cardiac filling pressures will be assessed by echocardiography with Doppler and strain analysis. CONCLUSIONS: This study will examine if furosemide leads to a hyperacute reduction in pulmonary congestion assessed by ReDS independent of diuretic effects in patients with AHF. We hypothesise that the haemodynamic effect of furosemide shown on pulmonary congestion may explain the subjective instant relief in patients with AHF receiving furosemide. FUNDING: Dr. Grand's salary during this project is supported by a research grant from the Danish Cardiovascular Academy funded by Novo Nordisk Foundation grant number NNF20SA0067242 and by the Danish Heart Foundation. TRIAL REGISTRATION: This protocol was approved by the Scientific Ethical Committee, H-23029822, and the Danish Data Protection Agency P-2013-14703. The protocol was registered with ClinicalTrial.org on 29 August 2023 (Identifier: NCT06024889).