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Ingunn Skjørten,1,2 Janne Mykland Hilde,3 Morten Nissen Melsom,1 Jonny Hisdal,4 Viggo Hansteen,5 Kjetil Steine,2,3 Sjur Humerfelt6 1Department of Pulmonary Medicine, LHL Hospital Gardermoen, Jessheim, 2Faculty of Medicine, University of Oslo, Oslo, 3Department of Cardiology, Akershus University Hospital, Lørenskog, 4Section of Vascular Investigations, Oslo University Hospital-Aker, 5Department of Cardiology, Oslo University Hospital-Aker, 6Clinic of Allergology and Respiratory Medicine, Oslo, Norway Background: Pulmonary hypertension (PH) in patients with COPD is associated with reduced exercise capacity. A subgroup of COPD patients has normal mean pulmonary artery pressure (mPAP) at rest, but develops high mPAP relative to cardiac output (CO) during exercise, a condition we refer to as exercise-induced pulmonary hypertension (EIPH). We hypothesized that COPD patients with EIPH could be identified by cardiopulmonary exercise test (CPET) and that these patients have lower exercise capacity and more abnormal CPET parameters compared to COPD patients with normal hemodynamic exercise response.Methods: Ninety-three stable outpatients with COPD underwent right heart catheterization with the measurement of mPAP, CO, and capillary wedge pressure at rest and during supine exercise. Resting mPAP

Ingunn Skjørten,1,2 Janne Mykland Hilde,3 Morten Nissen Melsom,1 Jonny Hisdal,4 Viggo Hansteen,5 Kjetil Steine,2,3 Sjur Humerfelt6 1Department of Pulmonary Medicine, LHL Glittre Clinic, Hakadal, 2Faculty of Medicine, University of Oslo, Oslo, 3Department of Cardiology, Akershus University Hospital, Lørenskog, 4Section of Vascular Investigations, 5Department of Cardiology, Oslo University Hospital-Aker, 6Clinic of Allergology and Respiratory Medicine, Oslo, Norway Background: Exercise tolerance decreases as COPD progresses. Pulmonary hypertension (PH) is common in COPD and may reduce performance further. COPD patients with and without PH could potentially be identified by cardiopulmonary exercise test (CPET). However, results from previous studies are diverging, and a unified conclusion is missing. We hypothesized that CPET combined with arterial blood gases is useful to discriminate between COPD outpatients with and without PH. Methods: In total, 93 COPD patients were prospectively included. Pulmonary function tests, right heart catheterization, and CPET with blood gases were performed. The patients were divided, by mean pulmonary artery pressure, into COPD-noPH (

We wanted to explore whether change in LA (left atrium) size would influence LA function, or increase regurgitation in the atrioventricular valves. 595 male elite football players and 47 non-athletic controls were included. End-systolic LA volume and RA area and end-diastolic LV volume and RV area were measured by 2-dimensional (2D) echocardiography Pulsed and colour Doppler were used to estimate tricuspid and mitral regurgitations. 2D longitudinal strain of the 50 football players with the largest LA volumes were compared with the 50 players with the smallest LA volumes. The LA volumes in some athletes with large atria were more than tripled, compared to athletes with small atria. 2D strain however, could not reveal any impairment of LA function in the players with the largest atria, compared to those with the smallest LA. Tricuspid valve regurgitation was found in 343 (58 %) of the athletes, compared to 17 (36 %) of the controls (p < 0.01), while mitral regurgitation was found in 116 (20 %) football players and 7 (15 %) controls (NS). Furthermore, the RA area was significantly larger in athletes with tricuspid regurgitation compared to athletes without. The present study demonstrated a huge variation in atrial size between the athletes. This variation, however, had no impact on LA function. Tricuspid regurgitation was significantly more prevalent among the athletes, than among the controls. [ABSTRACT FROM AUTHOR]

An abstract of the article "Subclinical impairment of LV function by tissue Doppler imaging in patients with osteogenesis imperfecta," by Z. Radunovic and colleagues is presented.

An abstract of the article "Impaired LV systolic longitudinal function by a new systolic index and LV diastolic dysfunction in patients with moderate aortic stenosis," by K. Steine and colleagues is presented.

An abstract of the article "LV systolic torsion is dependent while diastolic untwisting is independent of alterations in preload measured by 2-D speckle tracking imaging," by A. Hodt and colleagues is presented.

Many patients with chronic thromboembolic pulmonary disease (CTEPD) suffer from exertional dyspnea. It is unclear if CTEPD is associated with exercise pulmonary hypertension (ePH). This cross-sectional study aimed to determine the occurrence of ePH in patients with CTEPD and to identify the haemodynamic changes during exercise. We recruited 36 patients with persistent dyspnoea and residual perfusion defects by ventilation/perfusion scintigraphy from a large cohort of patients with previous pulmonary embolism. All patients underwent exercise right heart catheterization before being classified into the following groups: (1) CTEPD without ePH; comprising patients with normal mean pulmonary artery pressure (mPAP) of ≤20 mmHg, but with mPAP/cardiac output (CO) slope of ≤3 mmHg/L/min, (2) CTEPD with ePH (CTEPD-ePH); those with CTEPD with an mPAP/CO slope of >3 mmHg/L/min, (3) chronic thromboembolic pulmonary hypertension (CTEPH); those with mPAP >20 mmHg, pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance >2 WU. The postcapillary contribution during exercise was considered present if the PAWP/CO slope of >2 mmHg/L/min. CTEPD without resting pulmonary hypertension (PH) was present in 29 (81%) of the 36 patients, of whom six (21%) had ePH, while five (14%) had CTEPH. Two patients had unclassified PH. Two (33%) of the six patients with CTEPD-ePH had a PAWP/CO slope of >2 mmHg/L/min, compared with two (40%) of the five of those with CTEPH. In conclusion, about 20% of patients with CTEPD and exertional dyspnoea had ePH. Exercise right heart catheterization revealed a notable proportion of patients with postcapillary contribution., Competing Interests: K. Stavem reports consulting fees from MSD and Union Chimique Belge (UCB) unrelated to this study. W. G. reports fees for participation in an advisory board from Amgen, Novartis, Pfizer, Principia Biopharma Inc.—a Sanofi Company, Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, Alpine, Kedrion and HiBio; lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, Sanofi and Bayer; and research grants from Bayer, BMS/Pfizer, and UCB. The remaining authors declare no conflict of interest., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Purpose: To assess left atrial (LA) function in individuals with known paroxysmal atrial fibrillation (AF) compared with healthy and nonhealthy individuals without atrial fibrillation., Methods: The Akershus Cardiac Examination 1950 Study included 3,706 individuals all born in 1950. LA strain assessment of reservoir (LASr), conduit (LAScd) and contractile (LASct) functions were performed in all participants by investigators blinded to clinical data. Participants with cardiovascular disease, obesity, diabetes, pulmonary or renal disease were defined as nonhealthy, and those without as healthy. Patients with paroxysmal AF were identified through medical history and ECG documentation., Results: LA strain assessment was feasible in 3,229 (87%) of the participants (50% women). The healthy group (n = 758) had significantly higher LASr and LAScd than the nonhealthy (n = 2,376), but LASct was similar between the groups. Participants with paroxysmal AF had significantly lower values of all strain parameters than the other groups. Multivariable logistic regression showed a significantly reduced probability of having AF per standard deviation increase in LASr and LASct. A nonlinear restricted cubic spline model fitted better with the association of LASr with paroxysmal AF than the linear model, and LA strain values below the population mean associated with an increased probability of having AF, but for values above the population mean no such association was present., Conclusion: Compared to participants without AF, those with known paroxysmal AF had significantly lower values of all LA strain parameters during sinus rhythm. Lower values of LA strain were associated with a significantly increased probability of having AF., (© 2024 The Author(s). Echocardiography published by Wiley Periodicals LLC.)

Background: The impact of recent consensus definitions of cancer therapy-related cardiac dysfunction (CTRCD) from the European Society of Cardiology cardio-oncology guidelines on the reported incidence of CTRCD has not yet been assessed., Objectives: The aim of this study was to assess the: 1) cumulative incidence; 2) point prevalence during and after adjuvant therapy; and 3) prognostic value of CTRCD as defined by different asymptomatic CTRCD guideline criteria., Methods: The cumulative incidence and point prevalence of CTRCD were retrospectively assessed in 118 patients participating in the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial. Asymptomatic CTRCD was assessed using alternative cardiac troponin (cTn) 99th percentile upper reference limits (URLs) to define cTnT and cTnI elevation., Results: The cumulative incidence of moderate or severe CTRCD was low (1.7%), whereas the cumulative incidence of mild asymptomatic CTRCD was higher and differed markedly according to the biomarker criteria applied, ranging from 49.2% of patients when cTnT greater than the sex-specific 99th percentile URL was used to define cTn elevation to 9.3% when sex-neutral cTnI was used. The point prevalence of CTRCD was highest at the end of anthracycline therapy (47.8%) and was driven primarily by asymptomatic cTn elevation. CTRCD during adjuvant therapy was not prognostic for CTRCD at extended follow-up of 24 months (Q1-Q3: 21-29 months) after randomization., Conclusions: Mild asymptomatic CTRCD during adjuvant breast cancer therapy was frequent and driven mainly by cTn elevation and was not prognostic of subsequent CTRCD. The incidence of mild, asymptomatic CTRCD differed markedly depending on the cTn assay and whether sex-neutral or sex-dependent URLs were applied. (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy [PRADA]; NCT01434134)., Competing Interests: This work was supported by the South-Eastern Norway Regional Health Authority, the University of Oslo, the Extra Foundation for Health and Rehabilitation, Norway, the Norwegian Cancer Society, and Akershus University Hospital. Study medications and matching placebos were provided free of charge by AstraZeneca. Reagents for the analysis of high-sensitivity cTnI were provided by Abbott Diagnostics. Dr Gulati has received speaker honoraria from Novartis, AstraZeneca, and Bristol Myers Squibb. Dr Omland has served on advisory boards for Abbott Diagnostics, Roche Diagnostics, and Bayer; has received research support from Abbott Diagnostics, Novartis, and Roche Diagnostics via Akershus University Hospital; and has received speaker or consulting honoraria from Roche Diagnostics, Siemens Healthineers, and CardiNor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Introduction: Atrial fibrillation (AF) increases the risk for stroke, dementia, and impaired health-related quality of life (HRQL). Elective direct current cardioversion (ECV) is often used to restore sinus rhythm but is associated with thromboembolism. While larger strokes usually produce symptoms, subclinical ones may go unrecognized and may cause cognitive and functional decline over time. In the current study, we sought to evaluate the effects of ECV on silent brain infarctions and HRQL in patients with AF., Methods: Patients with AF (n = 46) underwent brain magnetic resonance imaging (MRI) and HRQL assessment using the EuroQL-5D5L questionnaire before and after ECV. Implantable loop recorders (ILRs) were used to observe the rate of early AF recurrences within the first 30 days. All patients were treated with anticoagulants according to guidelines. The primary endpoint was silent brain infarction assessed by brain MRI within the first 2 weeks after ECV. Secondary endpoints were the change in HRQL and its association with AF recurrence at follow-up and by ILR recordings., Results: New silent brain infarction after ECV was detected in 1 patient. At follow-up visit after 19.1 days AF recurrence was detected by 12-lead ECG in 13 patients (28.3%), whereas 27 patients (58.7%) had AF recurrence recorded by ILR within the first 30 days after ECV. European Heart Rhythm Association (EHRA) symptom score and the EuroQL-5d5L score were improved after ECV., Conclusion: Silent brain infarctions may occur after ECV despite anticoagulation treatment. Early AF recurrence is frequent. ECV positively affects HRQL mainly in those patients with sustained sinus rhythm at follow-up., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Persistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE). Rehabilitation is a potential treatment option, but the scientific evidence is limited., Research Question: Does an exercise-based rehabilitation program improve exercise capacity in PE survivors with persistent dyspnea?, Study Design and Methods: This randomized controlled trial was conducted at two hospitals. Patients with persistent dyspnea following PE diagnosed 6 to 72 months earlier, without cardiopulmonary comorbidities, were randomized 1:1 to either the rehabilitation or the control group. The rehabilitation program consisted of two weekly sessions of physical exercise for 8 weeks and one educational session. The control group received usual care. The primary end point was the difference in Incremental Shuttle Walk Test between groups at follow-up. Secondary end points included differences in the Endurance Shuttle Walk Test (ESWT), QoL (EQ-5D and Pulmonary Embolism-QoL questionnaires) and dyspnea (Shortness of Breath questionnaire)., Results: A total of 211 subjects were included: 108 (51%) were randomized to the rehabilitation group and 103 (49%) to the control group. At follow-up, participants allocated to the rehabilitation group performed better on the ISWT compared with the control group (mean difference, 53.0 m; 95% CI, 17.7-88.3; P = .0035). The rehabilitation group reported better scores on the Pulmonary Embolism-QoL questionnaire (mean difference, -4%; 95% CI, -0.09 to 0.00; P = .041) at follow-up, but there were no differences in generic QoL, dyspnea scores, or the ESWT. No adverse events occurred during the intervention., Interpretation: In patients with persistent dyspnea following PE, those who underwent rehabilitation had better exercise capacity at follow-up than those who received usual care. Rehabilitation should be considered in patients with persistent dyspnea following PE. Further research is needed, however, to assess the optimal patient selection, timing, mode, and duration of rehabilitation., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT03405480; URL: www., Clinicaltrials: gov., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Residual perfusion defects (RPD) after pulmonary embolism (PE) are common., Primary Aim: This study aimed to determine the prevalence of RPD in a cohort diagnosed with PE 6-72 months earlier, and to determine demographic, clinical, and echocardiographic variables associated with RPD., Methods: Patients aged 18-75 years with prior PE, confirmed by computed tomography pulmonary angiography 6-72 months earlier, were included. Participants (N = 286) completed a diagnostic work-up consisting of transthoracic echocardiography and ventilation/perfusion scintigraphy. Demographic, clinical, and echocardiographic characteristics between participants with RPD and those without RPD were explored in univariate analyses using t-test or Mann-Whitney U test. Multiple logistic regression analysis was used to assess the association between selected variables and RPD., Results: RPD were detected in 72/286 patients (25.2 %, 95 % CI:20.5 %-30.5 %). Greater tricuspid annular plane systolic excursion (TAPSE) (adjusted odds ratio (aOR) 1.10, 95 % CI:1.00-1.21, p = 0.048) at echocardiographic follow-up, greater thrombotic burden at diagnosis, as assessed by mean bilateral proximal extension of the clot (MBPEC) score 3-4 (aOR 2.08, 95 % CI:1.06-4.06, p = 0.032), and unprovoked PE (aOR 2.25, 95 % CI:1.13-4.48, p = 0.021) were independently associated with increased risk of RPD, whereas increased pulmonary artery acceleration time was associated with a lower risk of RPD (aOR 0.72, 95 % CI:0.62-0.83, p < 0.001, per 10 ms). Dyspnoea was not associated with RPD., Conclusion: RPD were common after PE. Reduced pulmonary artery acceleration time and greater TAPSE on echocardiography at follow-up, greater thrombotic burden at diagnosis, and unprovoked PE were associated with RPD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: F. Klok has received research support from Bayer, Bristol-Myers Squibb, Actelion, Boston Scientific, Leo Pharma, FarmX, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation and the Horizon Europe program, all outside this work and paid to his institution. K.Stavem reports consulting fees from MSD and UCB unrelated to this study. W.Ghanima reports fees for participation in Advisory board from Amgen, Novartis, Pfizer, Principia Biopharma Inc- a Sanofi Company, Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, and lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, Sanofi and Bayer. W.Ghanima reports research grants from Bayer, BMS/Pfizer and UCB. A.Dhayyat, D.Rashid, J.Gleditsch, K.Steine M.Tavoly, S.Haukeland-Parker, and Ø.Jervan declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pericarditis is an important differential diagnosis in patients with chest pain. The two most common causes in the developed world are idiopathic pericarditis and inflammation following cardiac surgery or myocardial infarction. Recurrence of pericarditis affects up to 30 % of patients, half of whom experience multiple episodes, and approximately 10 % develop steroid-dependent and colchicine-refractory pericarditis. Recurrence is due to autoinflammatory processes in the pericardium. Advanced diagnostic imaging and treatment with colchicine and interleukin-1 inhibitors has helped reduce morbidity considerably in recent years. In this clinical review, we summarise up-to-date knowledge about the diagnostic evaluation and treatment of patients with recurrent primary pericarditis.

Aims: Left atrial (LA) strain is promising in prediction of clinical atrial fibrillation (AF) in stroke patients. However, prediction of subclinical AF is critical in patients with embolic strokes of undetermined source (ESUS). The aim of this prospective study was to investigate novel LA and left atrial appendage (LAA) strain markers in prediction of subclinical AF in ESUS patients., Methods and Results: A total of 185 patients with ESUS, mean age 68 ± 13years, 33% female, without diagnosed AF, were included. LAA and LA function by conventional echocardiographic parameters and reservoir strain (Sr), conduit strain (Scd), contraction strain (Sct), and mechanical dispersion (MD) of Sr were assessed with transoesophageal and transthoracic echocardiography. Subclinical AF was detected by insertable cardiac monitors during follow-up. LAA strain was impaired in 60 (32%) patients with subclinical AF compared to those with sinus rhythm: LAA-Sr, 19.2 ± 4.5% vs. 25.6 ± 6.5% ( P < 0.001); LAA-Scd, -11.0 ± 3.1% vs. -14.4 ± 4.5% ( P < 0.001); and LAA-Sct, -7.9 ± 4.0% vs. -11.2 ± 4% ( P < 0.001), respectively, while LAA-MD was increased, 34 ± 24 ms vs. 26 ± 20 ms ( P = 0.02). However, there was no significant difference in phasic LA strain or LA-MD. By ROC analyses, LAA-Sr was highly significant in prediction of subclinical AF and showed the best AUC of 0.80 (95% CI 0.73-0.87) with a sensitivity of 80% and a specificity of 73% ( P < 0.001). LAA-Sr and LAA-MD were both independent and incremental markers of subclinical AF in ESUS patients., Conclusion: LAA function by strain and mechanical dispersion predicted subclinical AF in ESUS patients. These novel echocardiographic markers may improve risk stratification in ESUS patients., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Atrial fibrillation is a common arrhythmia associated with risk of stroke, heart failure and death. We aimed to elucidate the associations of cardiac biomarkers, echocardiographic left atrial volumetric indices and risk of prevalent and incident atrial fibrillation in the general population., Methods: We assessed cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), maximum (LAVi max ) and minimum (LAVi min ) indexed left atrial volumes and left atrial emptying fraction (LAEF) in subjects born in 1950 participating in the prospective observational cohort, Akershus Cardiac Examination 1950 Study. The Cohorts for Heart and Ageing Research in Genomic Epidemiology for Atrial Fibrillation risk score and sex was used to adjust for residual risk of atrial fibrillation., Results: Out of 3487 subjects, 157 (4.5%) had prevalent and 123 (3.5%) had incident atrial fibrillation. Echocardiographic left atrial volumes and cardiac biomarkers associated with prevalent atrial fibrillation, but GDF-15 was non-significant in adjusted analysis. Incident atrial fibrillation was predicted by LAVi max (adjusted HR 1.51, 95% CI 1.30 to 1.75), LAVi min (adjusted HR 1.52, 95% CI 1.35 to 1.72), LAEF (adjusted HR 1.24, 95% CI 1.04 to 1.48) and NT-proBNP (adjusted HR 1.57, 95% CI 1.32 to 1.85). cTnT and NT-proBNP provided incremental prognostic information to left atrial volumes, but GDF-15 demonstrated no prognostic value for incident atrial fibrillation., Conclusions: In the general population, echocardiographic left atrial volumetric indices and NT-proBNP, but not cTnT and GDF-15, associate with prevalent atrial fibrillation and with risk of incident atrial fibrillation. cTnT and NT-proBNP provide incremental prognostic information to echocardiography., Competing Interests: Competing interests: TO has served on advisory boards for Abbott Diagnostics, Roche Diagnostics and Bayer, and has received research support from Abbott Diagnostics, Novartis, Roche Diagnostics, Singulex and SomaLogic via Akershus University Hospital, and speaker’s or consulting honoraria from Roche Diagnostics, Siemens Healthineers and CardioNor. TB has received speaker fees from Bayer, Boehringer Ingelheim, BMS and Pfizer (non-related to the submitted work). All other authors have no competing interests., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypertension is a risk factor for the development of cardiovascular disease. Whether serial blood pressure (BP) measurements are more closely associated with subclinical left ventricular (LV) remodelling and better predict risk of cardiovascular events over individual BP measurements are not known., Methods: We assessed systolic BP, diastolic BP and pulse pressure at several time points during adulthood in 1333 women and 1211 men participating in the Akershus Cardiac Examination 1950 Study. We defined serial BP measurements as the sum of averaged BPs from adjacent consecutive visits indexed to total exposure time between measurements. We assessed the associations between serial and individual BP measurements and (1) LV structure, function and volumes and (2) incident myocardial infarction, ischemic stroke, heart failure and cardiovascular death., Results: All indices of higher serial BP measurements were associated with increased indexed LV mass, and the associations were stronger than those of individual BP measurements. Serial diastolic BP pressure was strongly and inversely associated with LV systolic function, while higher serial systolic BP was primarily associated with higher LV volumes. Both serial systolic (incidence rate ratio [IRR] 1.10, 95% CI 1.03 to 1.17) and diastolic BPs (IRR 1.14, 95% CI 1.02 to 1.27) were associated with increased incidence of clinical events., Conclusion: In healthy community dwellers without established cardiovascular disease, different serial BP indices associate strongly with LV remodelling and cardiovascular outcomes. Whether the use of serial BP indices for guiding treatment is superior to individual measurements should be explored in additional prospective studies., (© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Aims: Studies with implantable cardiac monitors (ICMs) show that one-third of patients with cryptogenic stroke/transient ischaemic attack (TIA) have episodes of subclinical atrial fibrillation (SCAF) and benefit switching from antiplatelet- to anticoagulant therapy. However, ICMs are costly and resource demanding. We aimed to build a score based on participant's baseline characteristics that could assess individual risk of SCAF., Methods and Results: In a prospective study, 236 eligible patients with a final diagnosis of cryptogenic stroke/TIA had an ICM implantated during the index hospitalization. Pre-specified evaluated variables were: CHA2DS2-VASc, P-wave duration, P-wave morphology, premature atrial beats (PAC)/24 h, supraventricular tachycardia/24 h, left atrial end-systolic volume index (LAVI), Troponin-T, NT-proBNP, and D-dimer. SCAF was detected in 84 patients (36%). All pre-specified variables were significantly associated with SCAF detection in univariate analysis. P-wave duration, followed by PAC/24 h, NT-proBNP, and LAVI, had the largest ratio of SCAF prevalence between its upper and lower quartiles (3.3, vs. 3.2, vs. 3.1 vs. 2.8, respectively). However, in a multivariate analysis, only PAC/24t, P-wave duration, P-wave morphology, and LAVIs remained significant predictors and were included in the PROACTIA score. Subclinical atrial fibrillation prevalence was 75% in the highest vs. 10% in the lowest quartile of the PROACTIA score with a 10-fold higher number of patients with an atrial fibrillation burden >6 h in the highest vs. the lowest quartile., Conclusion: The PROACTIA score can identify patients with cryptogenic stroke/TIA at risk of subsequent SCAF detection. The large difference in SCAF prevalence between groups may provide a basis for future tailored therapy., Clinical Trial Registration: Clinical Trial Registration: ClinicalTrials.gov; NCT02725944., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Abuse of anabolic-androgenic steroids (AAS) has been linked to a variety of different cardiovascular (CV) side effects, but still the clinical effects of AAS abuse on CV risk are not clear. The aim of this study was to assess the CV phenotype of a large cohort of men with long-term AAS use compared with strength-trained athletes without AAS use., Methods: Fifty one strength-trained men with ≥3 years of AAS use was compared with twenty one strength-trained competing athletes. We verified substance abuse and non-abuse by blood and urine analyses. The participants underwent comprehensive CV evaluation including laboratory analyses, 12-lead ECG with measurement of QT dispersion, exercise ECG, 24 h ECG with analyses of heart rate variability, signal averaged ECG, basic transthoracic echocardiography, and coronary computed tomography angiography (CCTA)., Results: Hemoglobin levels and hematocrit were higher among the AAS users compared with non-users (16.8 vs. 15.0 g/dl, and 0.50% vs. 0.44%, respectively, both p < 0.01) and HDL cholesterol significantly lower (0.69 vs. 1.25 mmol/L, p < 0.01). Maximal exercise capacity was 270 and 280 W in the AAS and the non-user group, respectively (p = 0.04). Echocardiography showed thicker intraventricular septum and left ventricular (LV) posterior wall among AAS users (p < 0.01 for both), while LV ejection fraction was lower (50 vs. 54%, p = 0.02). Seven AAS users (17%) had evidence of coronary artery disease on CCTA. There were no differences in ECG measures between the groups., Conclusions: A divergent CV phenotype dominated by increased CV risk, accelerated coronary artery disease, and concentric myocardial hypertrophy was revealed among the AAS users., (© 2022 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Aims: Pulmonary hypertension (PHT) may complicate heart failure with reduced ejection fraction (HFrEF) and is associated with a substantial symptom burden and poor prognosis. Sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, might have beneficial effects on pulmonary haemodynamics, cardiac function and exercise capacity in HFrEF and PHT. The aim of this study was to determine the safety, tolerability, and efficacy of sildenafil in patients with HFrEF and indirect evidence of PHT., Methods and Results: The Sildenafil in Heart Failure (SilHF) trial was an investigator-led, randomized, multinational trial in which patients with HFrEF and a pulmonary artery systolic pressure (PASP) ≥40 mmHg by echocardiography were randomly assigned in a 2:1 ratio to receive sildenafil (up to 40 mg three times/day) or placebo. The co-primary endpoints were improvement in patient global assessment by visual analogue scale and in the 6-min walk test at 24 weeks. The planned sample size was 210 participants but, due to problems with supplying sildenafil/placebo and recruitment, only 69 patients (11 women, median age 68 (interquartile range [IQR] 62-74) years, median left ventricular ejection fraction 29% (IQR 24-35), median PASP 45 (IQR 42-55) mmHg) were included. Compared to placebo, sildenafil did not improve symptoms, quality of life, PASP or walk test distance. Sildenafil was generally well tolerated, but those assigned to sildenafil had numerically more serious adverse events (33% vs. 21%)., Conclusion: Compared to placebo, sildenafil did not improve symptoms, quality of life or exercise capacity in patients with HFrEF and PHT., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background Echocardiographic measures of left atrial volumes are powerful predictors of cardiovascular events and important for assessing diastolic dysfunction. Despite this, there is limited knowledge of factors influencing left atrial remodeling. In particular, the impact of blood pressure in those in their early 40s on left atrial volumes later in life has not been sufficiently elucidated. Methods and Results We linked data from individuals born in 1950 who participated in the Age 40 Program, and the ACE (Akershus Cardiac Examination) 1950 Study. We divided the study population into quartiles of systolic blood pressure in their early 40s and assessed the proportion of individuals with an enlarged left atrium in their mid-60s. The associations between blood pressure and left atrial volumes were assessed in linear regression analyses. Of the 2591 individuals included in this study, 1302 (50.3%) were women, and the mean age in the Age 40 Program was 40.1±0.3 years. Systolic blood pressure was 128.1±13.6 mm Hg and diastolic blood pressure was 78.3±9.5 mm Hg. Mean age in the ACE 1950 Study was 64.0±0.6 years. The proportion of individuals with an enlarged left atrium increased across the quartiles of systolic blood pressure ( P =0.001). Systolic blood pressure was independently associated with left atrial volumes; the end-systolic volume was 0.09 mL (95% CI, 0.04-0.14 mL) larger per 1-mm Hg higher systolic blood pressure. Conclusions Our findings suggest that increased blood pressure in those in their early 40s is relevant for left atrial remodeling later in life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01555411.

Aims: Mechanical dispersion measures left ventricular contraction heterogeneity and is associated with the risk of sudden cardiac death. However, the associations between mechanical dispersion and cardiovascular risk factors in early mid-life, and established biomarkers of sub-clinical myocardial injury and dysfunction are not known. We aimed to examine this in the general population., Methods and Results: During 2012-15, we included 2527 Norwegian individuals from the general population born in 1950, with measurements of mechanical dispersion by 2D speckle tracking echocardiography and concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) available. Mechanical dispersion was calculated as the standard deviation of the contraction duration of 17 strain segments. We assessed the associations between mechanical dispersion, concentrations of hs-cTnT and NT-proBNP, and cardiovascular risk factors collected at a national health screening survey two decades earlier. At echocardiography baseline, median age was 64 (interquartile range 63.5-64.5) years, 49.8% were women, 59.1% had hypertension, and 5.9% reported established coronary artery disease. Median mechanical dispersion was 38.0 (29.5-47.0) ms, median hs-cTnT concentration 6 (4-8) ng/L, and the median NT-proBNP concentration 54 (34-93) ng/L. Mechanical dispersion was associated with both hs-cTnT and NT-proBNP concentrations in multivariable models adjusted for clinical and echocardiographic variables. High body mass index, serum triglyceride concentrations, and low resting heart rate at Age 40 were independently associated with increased mechanical dispersion two decades later., Conclusion: Established risk factors at Age 40 are associated with mechanical dispersion two decades later, and mechanical dispersion is cross-sectionally associated with biomarkers of subclinical myocardial injury and dysfunction., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Adjuvant breast cancer therapy containing anthracyclines with or without anti-human epidermal growth factor receptor-2 antibodies and radiotherapy is associated with cancer treatment-related cardiac dysfunction. In the PRADA trial (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy), concomitant treatment with the angiotensin receptor blocker candesartan attenuated the reduction in left ventricular ejection fraction (LVEF) in women receiving treatment for breast cancer, whereas the β-blocker metoprolol attenuated the increase in cardiac troponins. This study aimed to assess the long-term effects of candesartan and metoprolol or their combination to prevent a reduction in cardiac function and myocardial injury., Methods: In this 2×2 factorial, randomized, placebo-controlled, double-blind, single-center trial, patients with early breast cancer were assigned to concomitant treatment with candesartan cilexetil, metoprolol succinate, or matching placebos. Target doses were 32 and 100 mg, respectively. Study drugs were discontinued after adjuvant therapy. All 120 validly randomized patients were included in the intention-to-treat analysis. The primary outcome measure was change in LVEF assessed by cardiovascular magnetic resonance imaging from baseline to extended follow-up. Secondary outcome measures included changes in left ventricular volumes, echocardiographic peak global longitudinal strain, and circulating cardiac troponin concentrations., Results: A small decline in LVEF but no significant between-group differences were observed from baseline to extended follow-up, at a median of 23 months (interquartile range, 21 to 28 months) after randomization (candesartan, 1.7% [95% CI, 0.5 to 2.8]; no candesartan, 1.8% [95% CI, 0.6 to 3.0]; metoprolol, 1.6% [95% CI, 0.4 to 2.7]; no metoprolol, 1.9% [95% CI, 0.7 to 3.0]). Candesartan treatment during adjuvant therapy was associated with a significant reduction in left ventricular end-diastolic volume compared with the noncandesartan group ( P =0.021) and attenuated decline in global longitudinal strain ( P =0.046) at 2 years. No between-group differences in change in cardiac troponin I and T concentrations were observed., Conclusions: Anthracycline-containing adjuvant therapy for early breast cancer was associated with a decline in LVEF during extended follow-up. Candesartan during adjuvant therapy did not prevent reduction in LVEF at 2 years, but was associated with modest reduction in left ventricular end-diastolic volume and preserved global longitudinal strain. These results suggest that a broadly administered cardioprotective approach may not be required in most patients with early breast cancer without preexisting cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01434134.

Background Diabetes mellitus (DM) is associated with left ventricular remodeling and incident heart failure, but the association between glycated hemoglobin A1c (HbA1c) and subclinical cardiac disease is not established. We aimed to determine the associations between HbA1c and (1) echocardiographic measures of left ventricular structure and function, and (2) cardiovascular biomarkers: cardiac troponin T, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and CRP (C-reactive protein). Methods and Results Participants (n=3688) born in 1950 from the population-based ACE (Akershus Cardiac Examination) 1950 Study were classified as DM (HbA1c≥6.5% or self-reported DM), pre-DM (HbA1c 5.7%-6.5%), and no-DM (HbA1c<5.7%). DM, pre-DM, and no-DM were classified in 380 (10%), 1630 (44%), and 1678 (46%) participants, respectively. Mean age was 63.9±0.7 years, mean body mass index was 27.2±4.4 kg/m 2 , and 49% were women. Higher HbA1c was associated with worse left ventricular systolic (ejection fraction and global longitudinal strain) and diastolic (E/e'-ratio) function, myocardial injury (cardiac troponin T), inflammation (CRP), and impaired neurohormonal homeostasis (NT-proBNP) ( P <0.001 in unadjusted and P <0.01 in adjusted analysis for all). The associations between HbA1c and cardiovascular biomarkers were independent of the echocardiographic variables, and vice versa. Associations were nonlinear ( P <0.05 for nonlinearity) and appeared stronger in the pre-DM range of HbA1c than the no-DM and DM range. Conclusions HbA1c was associated with indexes of subclinical cardiovascular disease, and this was more pronounced in pre-DM. Our results suggest that cardiovascular preventive measures should be considered also in subjects with hyperglycemia and HbA1c below the established DM cutoff. Registration clinicaltrials.gov. Identifier: NCT01555411.

Introduction: Persistent dyspnea is common in follow-up after pulmonary embolism (PE), but the underlying mechanisms are poorly understood., Material and Methods: This cross-sectional study included subjects aged 18-75 years with confirmed PE by computed tomography pulmonary angiography (CTPA) 6-72 months earlier. A total of 180 participants underwent clinical examination, incremental shuttle walk test, laboratory tests, transthoracic echocardiography, pulmonary function tests and ventilation/perfusion scintigraphy. In further analysis, we divided participants into two groups; "dyspnea" or "no dyspnea", based on interview and questionnaires at inclusion. The association of cardiac and pulmonary variables with persistent dyspnea was assessed using multiple logistic regression analysis., Results: In total, 44% (95% CI: 39%-51%) of the participants reported persistent dyspnea after PE. Age (adjusted odds ratio (aOR) 0.93 per year, 95% CI: 0.90-0.97, P = 0.001), body mass index (BMI) (aOR 1.14 per kg/m 2 , 95% CI: 1.04-1.25, P = 0.004), recurrent venous thromboembolism (VTE) (aOR 3.69, 95% CI: 1.45-9.38, P = 0.006) and diffusion capacity of the lung for carbon monoxide (DLCO) (aOR 0.95 per increase of 1%, 95% CI: 0.92-0.98, P = 0.001) were independently associated with persistent dyspnea., Conclusions: Persistent dyspnea was prevalent after PE. Age, BMI and recurrent VTE were independently associated with dyspnea. Apart from reduced DLCO, no other cardiac or pulmonary variables were associated with persistent dyspnea., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Concentrations of B-type natriuretic peptide (BNP) reflect myocardial distension and stress, and are associated with poor prognosis in patients with cardiovascular disease. Accordingly, we hypothesized that concentrations of BNP would be associated with indices of adverse left ventricular (LV) remodeling and early stages of LV systolic and diastolic dysfunction in healthy participants from the general population., Methods: We measured BNP in 1757 women and 1677 men free from known coronary heart disease participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants underwent extensive cardiovascular phenotyping at baseline, including detailed echocardiography with assessment of indexed LV mass (LVMI), diastolic [tissue Doppler e', E/e' ratio, indexed left atrial volume (LAVI), maximal tricuspid regurgitation velocity (TRVmax), and E/A ratio], and systolic [global longitudinal strain (GLS) and LV ejection fraction (LVEF)] function., Results: Study participants with the highest BNP concentrations had higher GLS, LVMI, e', E/e' ratio, LAVI, TRVmax, and E/A ratio. In adjusted analyses, both GLS and LVEF exhibited significant nonlinear associations with BNP, with reduced LV systolic function observed in both the low and high concentration range of BNP., Conclusions: In healthy participants recruited from the general population, concentrations of BNP exhibit nonlinear associations with LV systolic function, and both low and high concentrations are associated with reduced LV systolic function. This supports the notion that natriuretic peptides are beneficial and elicit cardioprotective effects, and may have important implications for the interpretation of BNP measurements in the general population., (© American Association for Clinical Chemistry 2020.)

Background: Recently, a large group of patients with persistent dyspnea, poor physical capacity, and reduced health-related quality of life (HRQoL) following pulmonary embolism (PE) has been identified and clustered under the name "post pulmonary embolism syndrome" (PPS). These patients seem good candidates for pulmonary rehabilitation. The aim of the study is to explore whether a pulmonary rehabilitation program can improve physical capacity, dyspnea, and HRQoL in PPS patients., Methods: A two-center randomized controlled trial (RCT) is being performed at Østfold Hospital and Akershus University Hospital in Norway. Patients with PPS are 1:1 randomized into an intervention or a control group. The intervention consists of a supervised, outpatient rehabilitation program twice weekly (1 h) for 8 weeks provided by experienced physiotherapists. The intervention involves individually adapted exercises based on existing pulmonary rehabilitation programs (relaxation, interval, and resistance training), and an educational session including topics such as normal anatomy and physiology of the respiratory and circulatory system, information on PE/PPS, breathing strategies, and benefits of exercise/physical activity. Patients randomized to the control group receive usual care without specific instructions to exercise. Participants in the intervention and control groups will be compared based on assessments conducted at baseline, 12 weeks, and 36 weeks after inclusion using the incremental shuttle walk test (primary outcome) and endurance shuttle walk test (exercise capacity), Sensewear activity monitor (daily physical activity), the modified Medical Research Council scale, the Shortness of Breath Questionnaire (dyspnea), and EQ-5D-5L and the Pulmonary Embolism Quality of Life Questionnaire (HRQoL). Recruitment of 190 patients is currently ongoing., Discussion: Results from this study may provide a currently untreated group of PPS patients with an effective treatment resulting in reduced symptoms of dyspnea, improved exercise capacity, and better HRQoL following PE., Trial Registration: Clinical Trials NCT03405480 . Registered prospectively on September 2017. Protocol version 1 (from original protocol September 2017). The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 1).

Objectives: We aimed to assess prevalence of left ventricular (LV) systolic and diastolic function in stable cohort of COPD patients, where LV disease had been thoroughly excluded in advance., Methods: 100 COPD outpatients in GOLD II-IV and 34 controls were included. Patients were divided by invasive mean pulmonary artery pressure (mPAP) in COPD-PH (≥25 mmHg) and COPD-non-PH (<25 mmHg), which was subdivided in mPAP ≤20 mmHg and 21-24 mmHg. LV myocardial performance index (LV MPI) and strain by tissue Doppler imaging (TDI) were used for evaluation of LV global and systolic function, respectively. LV MPI ≥0.51 and strain ≤-15.8% were considered abnormal. LV diastolic function was assessed by the ratio between peak early (E) and late (A) velocity, early TDI E´, E/E´, isovolumic relaxation time, and left atrium volume., Results: LV MPI ≥0.51 was found in 64.9% and 88.5% and LV strain ≤-15.8% in 62.2.% and 76.9% in the COPD-non-PH and COPD-PH patients, respectively. Similarly, LV MPI and LV strain were impaired even in patients with mPAP <20 mmHg. In multiple regression analyses, residual volume and stroke volume were best associated to LV MPI and LV strain, respectively. Except for isovolumic relaxation time, standard diastolic echo indices as E/A, E´, E/E´ and left atrium volume did not change from normal individuals to COPD-non-PH., Conclusions: Subclinical LV systolic dysfunction was a frequent finding in this cohort of COPD patients, even in those with normal pulmonary artery pressure. Evidence of LV diastolic dysfunction was hardly present as measured by conventional echo indices., Competing Interests: The authors have declared that no competing interests exist.

Aims: The current study aimed to describe normal values of left atrial (LA) volumes and LA emptying fraction (LAEF) in a large sample in their mid-60s from the general population and to explore sex differences., Methods and Results: In the Akershus Cardiac Examination (ACE) 1950 Study, body surface area-indexed LA maximum (LAVimax) and minimum (LAVimin) volumes and LAEF were measured in 3489 individuals aged 63.9 ± 0.6 years from the general population. A healthy group of 832 individuals was defined. Data are presented as mean ± standard deviation (SD) and a normal range of mean ± 2 SD. T-tests were used for comparisons. In the healthy group, mean LAVimax was 25.5 ± 6.2 mL/m2 and the normal range was 13.1-37.9 mL/m2. Men had significantly larger body surface area-indexed volumes than women, but there was no difference in LAEF. The mean LAVimax for healthy men was 26.4 ± 6.5 mL/m2, for healthy women 24.9 ± 5.8 mL/m2 (P < 0.001) and the upper normal limits were 39.4 and 36.5 mL/m2, respectively. In the healthy group, 13.0% of all men and 5.4% of all women had LAVimax above the current upper normal limit of 34 mL/m2., Conclusion: A large proportion of healthy individuals, in particular men, had LAVimax >34 mL/m2. Our findings suggest that the recommended cut-off may be too low at the age of 65 years and above and that sex-specific cut-offs should be considered., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Concentrations of cardiac troponin I (cTnI) and T (cTnT) are associated with clinical cardiac outcomes, but do not correlate closely in subjects recruited from the general population. Accordingly, we hypothesized that cTnI and cTnT concentrations would be influenced by different cardiovascular (CV) and non-CV risk factors and reflect different CV phenotypes., Methods: We measured cTnI and cTnT with last generation assays in 1236 women and 1157 men with no known CV disease participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants underwent extensive CV phenotyping at baseline, including detailed echocardiography., Results: Concentrations of cTnI were measurable in 60.3% and cTnT in 72.5% of study participants (P < 0.001), and correlated moderately (r = 0.53; P < 0.001). cTnI was more strongly associated with male sex (P = 0.018), higher education (P < 0.001), history of hypertension (P < 0.001), and age (P < 0.001), whereas cTnT was more strongly associated with eGFR (P = 0.015). Both cTnI and cTnT were inversely associated with global longitudinal strain and positively associated with LV mass index (LVMI) in analyses adjusted for CV risk factors. The association between cTnI and LVMI was stronger than the association between cTnT and LVMI (P = 0.035). Concentrations of cTnI improved diagnostic accuracy for LV hypertrophy when added to established CV risk factors, but concentrations of cTnT did not improve these models further., Conclusions: In a large community-based cohort examined with extensive echocardiography, concentrations of cTnI and cTnT are associated with subclinical LV hypertrophy and dysfunction. Concentrations of cTnI appear superior to cTnT in predicting subclinical LV hypertrophy., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)