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Ejvind Frausing Hansen,1 Jens Dahlgaard Hove,1 Charlotte Sandau Bech,1 Jens-Ulrik Stæhr Jensen,2 Thomas Kallemose,3 Jørgen Vestbo4 1Medical Unit, Amager and Hvidovre Hospital, Copenhagen, Denmark; 2Medical Department, Herlev and Gentofte Hospital, Copenhagen, Denmark; 3Clinical Research Center, Amager and Hvidovre Hospital, Copenhagen, Denmark; 4School of Biological Sciences, University of Manchester and Manchester University NHS Foundation Trust, Manchester, UK Purpose: It is a challenge to control oxygen saturation (SpO2) in patients with exacerbations of COPD during admission. We tested a newly developed closed-loop system, O2matic®, and its ability to keep SpO2 within a specified interval compared with manual control by nursing staff. Patients and methods: We conducted a crossover trial with patients admitted with an exacerbation of COPD and hypoxemia (SpO2 ≤88% on room air). Patients were monitored with continuous measurement of SpO2. In random order, they had 4 hours with manually controlled oxygen and 4 hours with oxygen delivery controlled by O2matic. Primary outcome was time within a prespecified SpO2 target interval. Secondary outcomes were time with SpO2

Impaired myocardial flow reserve (MFR) has been demonstrated in hypertension, and has been associated with peripheral vascular changes. We investigated whether MFR was impaired and associated with structural and/or functional vascular changes in hypertensive patients without evidence of coronary artery disease (CAD). We measured left ventricular (LV) mass index by echocardiography and MFR by positron emission tomography in 33 unmedicated, hypertensive patients with electrocardiographic LV hypertrophy without CAD, and 15 age- and gender-matched normotensive subjects. We also measured 24-h ambulatory blood pressure, minimal forearm vascular resistance (MFVR) by plethysmography, media:lumen ratio in isolated, subcutaneous resistance arteries by myography, intima-media cross-sectional area of the common carotid artery, and flow-mediated (FMD) and nitroglycerin-induced dilatation (NID) of the brachial artery by ultrasound. Compared to the controls, the patients had impaired MFR (2.4 (95% CI 1.95-2.8) vs 3.4 (2.7-4.2), P<0.01) due to increased resting myocardial blood flow (MBF) (0.82 (0.73-0.91) vs 0.65 (0.56-0.75)?ml/g?min), and decreased dipyridamole-stimulated MBF (1.80 (1.55-2.1) vs 2.3 (1.80-2.8) ml/g?min, both P<0.05). The difference in resting MBF disappeared (80 (74-87) vs 86 (74-97)?µl/kg?mmHg, NS) when normalized for blood pressure and heart rate. MFR correlated negatively to median 24-h systolic blood pressure (r=-0.50, P<0.01) as well as to LV mass index (r=-0.45, P<0.05) and MFVR in men (r=-0.47, P<0.05), and positively to FMD (r=0.44, P<0.05) and NID (r=0.40, P<0.05). Hypertensive patients with electrocardiographic LV hypertrophy without CAD had impaired MFR associated with cardiovascular hypertrophy and vasodilatory dysfunction. This suggests that MFR is impaired by LV hypertrophy and structural/functional vascular damage in the coronary and noncoronary circulation.Journal of Human Hypertension (2004) 18, 445-452. doi:10.1038/sj.jhh.1001716 Published online 11 March 2004 [ABSTRACT FROM AUTHOR]

Background: Oxygen therapy is commonly administered to patients with acute cardiovascular conditions during hospitalisation. Both hypoxaemia and hyperoxia can cause harm, making it essential to maintain oxygen saturation (SpO 2 ) within a target range. Traditionally, oxygen administration is manually controlled by nursing staff, guided by intermittent pulse oximetry readings. This study aimed to compare standard manual oxygen administration with automated oxygen administration (AOA) using the O2matic device., Methods: In this randomised controlled trial, 60 patients admitted to a cardiac department with an acute cardiovascular condition requiring oxygen therapy were randomised to either standard care (manual oxygen administration) or AOA via the O2matic device. The primary outcome was the percentage of time spent within the desired SpO 2 range (92%-96% or 94%-98%) over 24 hours., Results: Patients had a mean age of 75.8±12.4 years, with an average SpO 2 of 93%. Those in the AOA group (n=25) spent significantly more time within the target SpO 2 range (median 87.0% vs 60.6%, p<0.001) compared with the standard care group (n=28). Time spent below the desired SpO 2 range was significantly lower in the AOA group (7.9% vs 33.6%, p<0.001). No significant differences in time spent above the desired SpO 2 range were observed between the two groups., Conclusions: AOA with the O2matic device is superior to standard manual control in maintaining SpO 2 within the target range in patients hospitalised with acute cardiovascular conditions. The automated systems significantly reduce the time spent in hypoxaemia without increasing hyperoxia., Trial Registration Number: NCT05452863., Competing Interests: Competing interests: Coauthors EFH and JDH hold shares in O2matic, and EFH is a board member; however, they did not receive any fees or support from O2matic in relation to this trial. The remaining authors did not report any conflicts of interest, (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Coronary tortuosity (CorT) is frequently observed in invasive angiography, though its aetiology and clinical significance remain ambiguous. Prior research has indicated possible links between CorT and factors such as hypertension, age, and calcium scores in the left anterior descending (LAD) artery. The aim of this study was to examine and optimize the usage of coronary computed tomography angiography (CCTA) with vessel tracking to explore these associations., Methods: Observational sub-study of the single centre randomised controlled CATCH-trial. From the original study 600 participants, who underwent CCTA, 250 were randomly selected. Clinical data and patient risk factors were sourced from medical records and structured interviews. Tortuosity of the LAD was quantified by calculating the ratio of the actual vessel-length to the straight-line distance., Results: The final study population comprised 194 patients (56 patients were excluded due to poor image quality or inability to perform adequate vessel tracking). After adjusting for confounding variables, tortuosity was significantly associated with hypertension (p < 0.001), female gender (p = 0.01), and increasing age (p = 0.045). No significant correlation was observed between CorT and calcium scores. Univariate analysis indicated that higher CorT levels were linked to lower metabolic equivalents of task (METs) in bicycle tests (p = 0.003); however, this relationship became nonsignificant (p = 0.97) upon adjustment for age, gender, and hypertension., Conclusions: Our findings suggest that increased CorT is most prevalent in patients with hypertension, advancing age, and female gender. Although higher tortuosity levels did not significantly impact METs during physical activity, further research is warranted to explore the underlying mechanisms of this relationship., (© 2024 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Background and Aims: Overtesting of low-risk patients with suspect chronic coronary syndrome (CCS) is widespread. The acoustic-based coronary artery disease (CAD) score has superior rule-out capabilities when added to pre-test probability (PTP). FILTER-SCAD tested whether providing a CAD score and PTP to cardiologists was superior to PTP alone in limiting testing., Methods: At six Danish and Swedish outpatient clinics, patients with suspected new-onset CCS were randomised to either standard diagnostic examination (SDE) with PTP, or SDE plus CAD score, and cardiologists provided with corresponding recommended diagnostic flowcharts. The primary endpoint was cumulative number of diagnostic tests at one year and key safety endpoint major adverse cardiac events (MACE)., Results: In total 2008 patients (46% male, median age 63 years) were randomised from October 2019 to September 2022. When randomised to CAD score (n=1002), it was successfully measured in 94.5%. Overall, 13.5% had PTP ≤5%, and 39.5% had CAD score ≤20. Testing was deferred in 22% with no differences in diagnostic tests between groups (p for superiority =0.56). In the PTP ≤5% subgroup, the proportion with deferred testing increased from 28% to 52% (p<0.001). Overall MACE was 2.4 per 100 person-years. Non-inferiority regarding safety was established, absolute risk difference 0.4% (95% CI -1.85 to 1.06) (p for non-inferiority = 0.005). No differences were seen in angina-related health status or quality of life., Conclusions: The implementation strategy of providing cardiologists with a CAD score alongside SDE did not reduce testing overall but indicated a possible role in patients with low CCS likelihood. Further strategies are warranted to address resistance to modifying diagnostic pathways in this patient population., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

To explore how nurses experience facilitators and barriers to the use of video-consultations for home-monitoring of patients with cardiac disease. A systematic literature search in PubMed, CINAHL, Scopus, and Web of Science was undertaken, inclusion criteria were qualitative data published between 2013 and 2023 written in English, Norwegian, Swedish, or Danish. Ten studies were included in the qualitative synthesis conducted as described by Braun and Clarke. From the synthesis, a main theme emerged: Nurses' uncertainty toward telemedicine is a risk toward the use of video-consultations and home-monitoring. The essence of the findings range from nurses' positive experiences to their frustration concerning the implementation process and the lack of technical support for clinicians and patients. Nurses often felt frustration and uncertainty about the quality of delivered care through virtual consultations. Working with technology in caring for patients with cardiac disease, including video-consultations and home-monitoring, nurses experienced a sense of insecurity. Insecurity was identified as a lack of technological knowledge, nurses' feelings of apathy, poorer observation through a video-consultation, and the lack of organizational support., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: Acute heart failure is a public health concern. This study systematically reviewed randomized clinical trials (RCTs) to evaluate vasodilators in acute heart failure., Methods: The search was conducted across the databases of Medline, Embase, Latin American and the Caribbean Literature on Health Sciences, Web of Science, and the Cochrane Central Register of Controlled Trials. Inclusion criteria consisted of RCTs that compared vasodilators versus standard care, placebo, or cointerventions. The primary outcome was all-cause mortality; secondary outcomes were serious adverse events (SAEs), tracheal intubation, and length of hospital stay. Risk of bias was assessed in all trials., Results: The study included 46 RCTs that enrolled 28,374 patients with acute heart failure. Vasodilators did not reduce the risk of all-cause mortality (risk ratio, 0.95; 95% confidence interval [CI], 0.87 to 1.04; I 2 =9.51%; P=0.26). No evidence of a difference was seen in the risk of SAEs (risk ratio, 1.01; 95% CI, 0.97 to 1.05; I 2 =0.94%) or length of hospital stay (mean difference, -0.10; 95% CI, -0.28 to 0.08; I 2 =69.84%). Vasodilator use was associated with a lower risk of tracheal intubation (risk ratio, 0.54; 95% CI, 0.30 to 0.99; I 2 =51.96%) compared with no receipt of vasodilators., Conclusions: In this systematic review with meta-analysis of patients with acute heart failure, vasodilators did not reduce all-cause mortality.

Objectives: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status., Materials and Methods: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications)., Results: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy., Conclusion: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers., Clinical Relevance Statement: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status., Trial Registration: ClinicalTrials.gov NCT02400229., Key Points: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

We recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in patients with Parkinson's disease compared to age- and sex-matched healthy controls. Since both groups showed substantial inter-individual variations, we extended the cohort of controls with a group of young individuals to investigate possible age-related effects. Seventeen healthy young subjects aged < 30 years and 17 elderly subjects aged > 50 years underwent serial PC-MRI to measure the postprandial blood flow response in the SMA after ingestion of a standardized liquid test meal (∼400 kcal). Postprandial blood flow dynamics in SMA did not differ between young and elderly subjects. A noticeable inter-individual variation in postprandial intestinal blood flow increase was found, and approximately 30% of the variation could be explained by the preprandial blood flow. Regardless of age, some subjects showed a remarkable transient SMA blood flow increase immediately after meal intake. This study provides tentative evidence that postprandial blood flow dynamics in SMA in healthy young and elderly subjects do not substantially differ, indicating that age is without impact on vascular response in SMA as an indicator for regulation of mesenteric perfusion in response to food intake., (© 2024. The Author(s).)

Introduction: Acute heart failure (AHF) is a critical, costly condition with high mortality rates, affecting millions annually. Despite advances in cardiovascular care, AHF treatment lacks robust evidence. AHF commonly manifests with sudden heart failure symptoms such as pulmonary congestion, and the pathophysiology involves fluid overload. Initial treatment is based on intravenous diuretics typically, but the optimal combination of drugs remains uncertain., Methods and Analysis: We will systematically review randomised controlled trials enrolling patients with AHF and volume overload undergoing in-hospital diuretic treatment. We aim to investigate any diuretic intervention. Our search strategy includes the following databases: Embase, Medline, Latin American and Caribbean Health Sciences Literature, Web of Science and the Cochrane Central Register of Controlled Trials. The primary outcome is all-cause mortality. Secondary outcomes are serious adverse events, hospital readmission and kidney failure. Study results reported at the most extended follow-up will be used for all outcomes. If appropriate, we will conduct meta-analysis, trial sequential analysis and network meta-analysis., Ethics and Dissemination: No ethics approval is required for this study. The results will be published in a peer-reviewed journal in this field., Prospero Registration Number: CRD42023463979., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The effectiveness and safety of computed tomography (CT) and invasive coronary angiography (ICA) in different age groups is unknown., Objective: To determine the association of age with outcomes of CT and ICA in patients with stable chest pain., Design, Setting, and Participants: The assessor-blinded Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial was conducted between October 2015 and April 2019 in 26 European centers. Patients referred for ICA with stable chest pain and an intermediate probability of obstructive coronary artery disease were analyzed in an intention-to-treat analysis. Data were analyzed from July 2022 to January 2023., Interventions: Patients were randomly assigned to a CT-first strategy or a direct-to-ICA strategy., Main Outcomes and Measures: MACE (ie, cardiovascular death, nonfatal myocardial infarction, or stroke) and major procedure-related complications. The primary prespecified outcome of this secondary analysis of age was major adverse cardiovascular events (MACE) at a median follow-up of 3.5 years., Results: Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 2360 (66.3%) were younger than 65 years, 982 (27.6%) were between ages 65 to 75 years, and 219 (6.1%) were older than 75 years. The primary outcome was MACE at a median (IQR) follow-up of 3.5 (2.9-4.2) years for 3523 patients (99%). Modeling age as a continuous variable, age, and randomization group were not associated with MACE (hazard ratio, 1.02; 95% CI, 0.98-1.07; P for interaction = .31). Age and randomization group were associated with major procedure-related complications (odds ratio, 1.15; 95% CI, 1.05-1.27; P for interaction = .005), which were lower in younger patients., Conclusions and Relevance: Age did not modify the effect of randomization group on the primary outcome of MACE but did modify the effect on major procedure-related complications. Results suggest that CT was associated with a lower risk of major procedure-related complications in younger patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02400229.

Background: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT)., Methods: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue., Results: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm 3 ; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm 3 ; patients with ACS: 370 [332-412] vs. 159 [139-182] mm 3 . After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm 3 , p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm 3 , p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm 3 ) compared to both asymptomatic individuals (15 [13-18] mm 3 , p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm 3 , p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm 3 , p>0.3 respectively., Conclusion: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not., Competing Interests: Declaration of competing interest All authors report no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous two years; and no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups ( P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed ( P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.

Liver diseases affect the heart and the vascular system. Cardiovascular complications appear to be a leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis. The predominant histological changes in the liver range from steatosis to fibrosis to cirrhosis, which can each affect the cardiovascular system differently. Patients with cirrhotic cardiomyopathy (CCM) and NAFLD are at increased risk of impaired systolic and diastolic dysfunction and for suffering major cardiovascular events. However, the pathophysiological mechanisms behind these risks differ depending on the nature of the liver disease. Accurate assessment of symptoms by contemporary diagnostic modalities is essential for identifying patients at risk, for evaluating candidates for treatment, and prior to any invasive procedures. This review explores current perspectives within this field., (© 2023. Asian Pacific Association for the Study of the Liver.)

Objective: To compare cardiac computed tomography (CT) with invasive coronary angiography (ICA) as the initial strategy in patients with diabetes and stable chest pain., Research Design and Methods: This prespecified analysis of the multicenter DISCHARGE trial in 16 European countries was performed in patients with stable chest pain and intermediate pretest probability of coronary artery disease. The primary end point was a major adverse cardiac event (MACE) (cardiovascular death, nonfatal myocardial infarction, or stroke), and the secondary end point was expanded MACE (including transient ischemic attacks and major procedure-related complications)., Results: Follow-up at a median of 3.5 years was available in 3,541 patients of whom 557 (CT group n = 263 vs. ICA group n = 294) had diabetes and 2,984 (CT group n = 1,536 vs. ICA group n = 1,448) did not. No statistically significant diabetes interaction was found for MACE (P = 0.45), expanded MACE (P = 0.35), or major procedure-related complications (P = 0.49). In both patients with and without diabetes, the rate of MACE did not differ between CT and ICA groups. In patients with diabetes, the expanded MACE end point occurred less frequently in the CT group than in the ICA group (3.8% [10 of 263] vs. 8.2% [24 of 294], hazard ratio [HR] 0.45 [95% CI 0.22-0.95]), as did the major procedure-related complication rate (0.4% [1 of 263] vs. 2.7% [8 of 294], HR 0.30 [95% CI 0.13 - 0.63])., Conclusions: In patients with diabetes referred for ICA for the investigation of stable chest pain, a CT-first strategy compared with an ICA-first strategy showed no difference in MACE and may potentially be associated with a lower rate of expanded MACE and major procedure-related complications., (© 2023 by the American Diabetes Association.)

Aims: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in type 1 (T1D) and type 2 diabetes (T2D). Despite diabetes affects the myocardium, risk prediction models do not include myocardial function parameters. Myocardial performance index (MPI) reflects left ventricular function. The prognostic value of MPI has not been evaluated in large-scale diabetes populations., Methods and Results: We evaluated two prospective cohort studies: Thousand&1 (1093 individuals with T1D) and Thousand&2 (1030 individuals with T2D). Clinical data, including echocardiography, were collected at baseline. We collected follow-up data from national registries. We defined major adverse cardiovascular events (MACE) as incident events of hospital admission for acute coronary syndrome, heart failure, stroke, or all-cause mortality. For included individuals (56% male, 54 ± 15 years, MPI 0.51 ± 0.1, 63% T1D), follow-up was 100% after median of 5.3 years (range: 4.8-6.3). MPI was associated with MACE (HR 1.2, 95%CI 1.0-1.3, P = 0.012, per 0.10-unit increase) and heart failure (HR 1.3, 95%CI 1.1-1.6, P = 0.005, per 0.10-unit increase) after adjusting for clinical and echocardiographic variables. MPI predicted MACE and heart failure better in T1D than T2D (P = 0.031 for interaction). MPI added discriminatory power to the Steno T1 Risk Engine, based on clinical characteristics, in predicting MACE [area under the curve (AUC) from 0.77 to 0.79, P = 0.030] and heart failure (AUC from 0.77 to 0.83, P = 0.009) in T1D., Conclusion: MPI is independently associated with MACE and heart failure in T1D but not T2D and improves prediction in T1D. Echocardiographic assessment in T1D may enhance risk prediction., Competing Interests: Conflict of interest: P.G.J. reports lecture fees from Astra Zeneca. U.D. has been an invited speaker for and received research grants from Bayer. T.B.-S. reports grants to his institution from Amgen, AstraZeneca, Boehringer, GE Healthcare, Novo Nordisk, and Sanofi Pasteur; has been on the advisory board of Amgen, GSK, and Sanofi Pasteur; and has received honoraria from Bayer, GSK, Novartis, and Sanofi Pasteur. P.R. reports grants to his institution from Astra Zeneca, Bayer, and Novo Nordisk and has received honoraria from Abbott, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi (all fees to the institution). M.T.J. has been a consultant, on advisory boards, or invited speaker for Astra Zeneca, GE, Novo Nordisk, and Novartis. All other authors have declared no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Non-selective beta-blockers (NSBB) are widely used in the treatment of patients with cirrhosis. Only about 50% respond with a sufficient reduction in their hepatic venous pressure gradient (HVPG) and NSBB may induce detrimental cardiac and renal effects in the presence of severe decompensation. We aimed to assess the effects of NSBB on haemodynamics using magnetic resonance imaging (MRI) and to assess if these haemodynamic changes were related to the disease severity and HVPG response., Method: A prospective cross-over study of 39 patients with cirrhosis. Patients underwent hepatic vein catheterization and MRI with assessments of HVPG, cardiac function, systemic and splanchnic haemodynamics before and after propranolol infusion., Results: Propranolol induced significant decreases in cardiac output (-12%) and blood flow of all vascular compartments, with the largest reductions seen in the azygos venous (-28%), portal venous (-21%), splenic (-19%) and superior mesenteric artery (-16%) blood flow. Renal artery blood flow fell by -5% in the total cohort, with a more pronounced reduction in patients without ascites than in those with ascites (-8% vs. -3%, p = .01). Twenty-four patients were NSBB responders. Their changes in HVPG after NSBB were not significantly associated with other haemodynamic changes., Conclusion: The changes in cardiac, systemic and splanchnic haemodynamics did not differ between NSBB responders and non-responders. The effects of acute NSBB blockade on renal flow seem to depend on the severity of the hyperdynamic state, with the largest reduction in renal blood flow in compensated patients compared to decompensated patients with cirrhosis. However, future studies are needed to assess the effects of NSBB on haemodynamics and renal blood flow in patients with diuretic-resistant ascites., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: With longer life expectancy in people living with HIV (PLWH) on antiretroviral therapy, cardiovascular disease (CVD) has become a common cause of mortality among them. Abacavir has been associated with an increased risk of myocardial infarction, but the mechanism is unknown. Additionally, abacavir may be obesogenic which could mediate an additional risk factor of CVD. We aim to investigate if discontinuation of abacavir will have a favourable impact on body weight and cardiac parameters in PLWH., Methods and Analysis: Randomised, controlled, superiority trial of virologically suppressed PLWH on dolutegravir, abacavir and lamivudine (DTG/ABC/3TC) for ≥6 months. In total, 70 PLWH will be randomised 1:2 to either continue DTG/ABC/3TC or to switch to dolutegravir and lamivudine (DTG/3TC) providing the power of 80% at alpha 5% to detect a mean difference in weight change of 2 kg (Δ) given an SD of 2.7 kg. Follow-up will be 48 weeks. Data will be collected at baseline and week 48. Primary outcome will be change in mean body weight from baseline to week 24 and 48 evaluated in a linear mixed model. Secondary outcomes will be changes in cardiac, inflammatory and metabolic parameters, fat distribution, coagulation, endothelial, platelet function, quality of life and virological control from baseline to week 48. Measurements include CT of thorax and abdomen, external carotid artery ultrasound, liver elastography and dual energy X-ray absorptiometry and blood analysis. Plasma HIV RNA will be measured at baseline, week 4, 24 and 48. Forty participants (20 from each arm) will be included in a substudy involving cardiac MRI at baseline and week 48. Twenty non-HIV-infected controls will be included with a single scan to compare with baseline scan data., Ethics and Dissemination: Result from this study will lead to a better understanding of the association between antiretroviral therapy and the impact on weight and risk of CVD. Findings will be useful for both clinicians and PLWH in the guidance of a more individualised HIV treatment. Results from the main study and the substudies will be submitted for publication in a peer-reviewed journal(s). The AVERTAS study is approved by the Ethics Committee of the Capital Region, Denmark (H-20011433), Danish Medicines Agency (EudraCT no. 2019-004999-19) and Regional Data Protection Centre (P-2020-207)., Trial Registration Number: Pre-results registration at ClinicalTrials.gov Identifier: NCT04904406, registered 27 May 2021., Protocol Version: Protocol version 9.0, 4 April 2023, approved 10-05-2023 by Ethics Committee of the Capital Region, Denmark (H-20011433). Danish Medicines Agency (EudraCT no. 2019-004999-19). Regional Data Protection Centre (P-2020-207) ClinicalTrials.gov., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Elevated serum bile acids (BA) are harmful to the heart and alterations in the BA composition have been suggested to cause cardiovascular disturbances in cirrhosis., Aim: To investigate any associations between specific groups or individual serum BA and structural and functional cardiac abnormalities in patients with cirrhosis., Methods: An explorative study in 86 patients with cirrhosis. All participants underwent extensive cardiac assessment, including cardiac MRI with quantification of myocardial extracellular volume (ECV), which is indicative of diffuse myocardial fibrosis. A panel of 15 individual serum BA and C4, a marker of de novo bile acid synthesis, were assessed., Results: Patients with advanced cirrhosis had higher levels of total BA and conjugated BA, as well as lower C4 levels (p < 0.001). Conjugated BA levels were higher in patients with a high cardiac index (p < 0.001), increased left atrial volume index (LAVI) (p < 0.001), and in those with an abnormal myocardial ECV (p < 0.05). We also found several strong correlations between conjugated BA, both as a group and individually, and parameters of cardiac dysfunction. In a model adjusted for sex, age, BMI and MELD, conjugated BA remained significantly associated with LAVI, septal e', left ventricular volumes and cardiac index. In addition, taurocholic acid correlated closely with hepatic venous pressure gradient (HVPG) (p = 0.01)., Conclusions: Increased serum concentrations of conjugated BA are associated with several cardiac parameters, indicating a potential role in the development of hyperdynamic circulation and cardiac dysfunction in cirrhosis. Moreover, taurine-conjugated BA are associated with portal hypertension., (© 2023 John Wiley & Sons Ltd.)

Aims: Patients suffering from chronic ischaemic heart failure with reduced left ventricular ejection fraction (HFrEF) have reduced quality-of-life, repetitive hospital admissions, and reduced life expectancy. Allogeneic cell therapy is currently investigated as a potential treatment option after initially encouraging results from clinical autologous and allogeneic trials in patients with HFrEF. We aimed to investigate the allogeneic Cardiology Stem Cell Centre Adipose tissue derived mesenchymal Stromal Cell product (CSCC&#95;ASC) as an add-on therapy in patients with chronic HFrEF., Methods and Results: This is a Danish multi-centre double-blinded placebo-controlled phase II study with direct intra-myocardial injections of allogeneic CSCC&#95;ASC. A total of 81 HFrEF patients were included and randomized 2:1 to CSCC&#95;ASC or placebo injections. The inclusion criteria were reduced left ventricular ejection fraction (LVEF ≤ 45%), New York Heart Association (NYHA) class II-III despite optimal anti-congestive heart failure medication and no further revascularization options. Injections of 0.3 mL CSCC&#95;ASC (total cell dose 100 × 10 6 ASCs) (n = 54) or isotonic saline (n = 27) were performed into the viable myocardium in the border zone of infarcted tissue using the NOGA Myostar® catheter (Biological Delivery System, Cordis, Johnson & Johnson, USA). The primary endpoint, left ventricular end systolic volume (LVESV), was evaluated at 6-month follow-up. The safety was measured during a 3-years follow-up period., Results: Mean age was 67.0 ± 9.0 years and 66.6 ± 8.1 years in the ASC and placebo groups, respectively. LVESV was unchanged from baseline to 6-month follow-up in the ASC (125.7 ± 68.8 mL and 126.3 ± 72.5 mL, P = 0.827) and placebo (134.6 ± 45.8 mL and 135.3 ± 49.6 mL, P = 0.855) group without any differences between the groups (0.0 mL (95% CI -9.1 to 9.0 mL, P = 0.992). Neither were there significant changes in left ventricular end diastolic volume or LVEF within the two groups or between groups -5.7 mL (95% CI -16.7 to 5.3 mL, P = 0.306) and -1.7% (95% CI -4.4. to 1.0, P = 0.212), respectively). NYHA classification and 6-min walk test did not alter significantly in the two groups (P > 0.05). The quality-of-life, total symptom, and overall summary score improved significantly only in the ASC group but not between groups. There were 24 serious adverse events (SAEs) in the ASC group and 11 SAEs in the placebo group without any significant differences between the two groups at 1-year follow-up. Kaplan-Meier plot using log-rank test of combined cardiac events showed an overall mean time to event of 30 ± 2 months in the ASC group and 29 ± 2 months in the placebo group without any differences between the groups during the 3 years follow-up period (P = 0.994)., Conclusions: Intramyocardial CSCC&#95;ASC injections in patients with chronic HFrEF were safe but did not improve myocardial function or structure, nor clinical symptoms., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Oxygen treatment of hypoxaemia is considered an essential part of the treatment of patients who are acutely admitted with medical conditions affecting cardiovascular and/or pulmonary function. Despite the important role of oxygen administration for these patients, clinical evidence on how to control supplemental oxygen to avoid hypoxaemia and hyperoxia is limited. We aim to investigate whether an automatic closed-loop oxygen administration system (O2matic) may maintain normoxaemia better than usual care., Methods: This study will be an investigator-initiated, prospective, randomised clinical trial. The patients are randomised during admission after informed consent is obtained, at a 1:1 ratio with conventional oxygen treatment or O2matic oxygen treatment for 24 hours. The primary outcome is time within the desired peripheral capillary oxygen saturation interval: 92-96%., Conclusion: This study will examine the clinical applicability of a novel automated feedback device termed O2matic and assess whether the device is superior to standard care in keeping the patients in the optimal saturation interval. We hypothesise that the O2matic will increase time within the desired saturation interval., Funding: Johannes 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., Clinicaltrials: gov (ClinicalTrials.gov Identifier: NCT05452863). Registered on 11 July 2022., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Aims: To evaluate a family-focused intervention for patients with atrial fibrillation (AF) in addition to conventional care and to establish its effect on health-related quality of life (HRQoL), anxiety, depression, AF symptoms, and family support., Background: AF is a widespread heart disease affecting the well-being of patients and their family members physically and psychologically. Supporting patients and their family members could potentially facilitate regaining family strength and improve HRQoL., Methods: Patients with newly diagnosed AF were randomised to standard care or additional family-focused intervention with change in global score of the Atrial Fibrillation Quality of Life Questionnaire (AFEQT) as primary outcome after six months' follow-up. Secondary outcomes included the Hospital Anxiety and Depression Score, the European Heart Rhythm Association score, the Ice Expressive Family Functioning Questionnaire, and the Ice Family-Perceived Support Questionnaire (ICE-FPSQ)., Results: Sixty-eight patients received standard care (n = 35) or family focused intervention (n = 33). The median change at the six-month follow-up on the global AFEQT score was 4.17 (-1.46-9.17) in the control group and 5.83 (-2.5-30) in the intervention group, yielding a median difference of -1.67 (p = 0.500). Change in ICE-FPSQ showed significant positive scores in favour of intervention (p < 0.001); other secondary outcome changes were non-significant., Conclusion: The family-focused intervention had a small positive but non-significant effect on HRQoL compared to standard care. To address the impact of AF on the patients and family members seems to improve anxiety and depression scores and perceived family support., Competing Interests: Enter: The authors have declared that no competing interests exist., (Copyright: © 2023 Rosenstrøm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Most medical educational programs emphasize clinical observation or clinical skill acquisition, fewer focus upon research. The Danish-American Research Exchange (DARE) program, sponsored by the Lundbeck Foundation, is unique in that the medical student initiates biomedical research collaboration between Danish and US medical institutions. To achieve this, Danish medical students (DARE students) conduct binational mentored research projects while based in the United States for 10 months. In addition, DARE students are introduced to interdisciplinary thinking about how to develop ultra-low-cost healthcare interventions through the '$10 Challenge'., Methods: We conducted a cross-sectional study of DARE alumni over five consecutive years (2015-2020, n = 24). Research metrics included completion of a research project, primary authorship, and co-authorship of publications. The number of publications, prior to and after the DARE program were enumerated. For the first four cohorts, graduation from medical school and acceptance or intention to enter a joint MD-PhD program also were assessed. Two focus groups were conducted using constructivist grounded theory. Discussions were transcribed, redacted, and coded using Dedoose software., Results: DARE Medical students were 31.2 years (range 24-35), the majority were women (67%;16/24). The majority (17/24;71%) completed a first author publication in a peer-reviewed journal with a median of 3.9 per DARE alumnus. DARE alumnus reported increased proficiency in biostatistics, epidemiology, coding and public speaking as well as stronger research qualities in creativity, critical thinking, comfort in approaching scientist in both the US and Denmark (p < 0.001 for all). Qualitative key themes included: increased confidence, a deepening of research inquiry and linkage to a research network., Conclusions: Preliminarily, this study suggests that medical students can initiate binational collaboration in medicine. Benefits include research productivity, intention to pursue academic medical careers, as well as positive impacts on motivation. This medical student-initiated research model lays the groundwork for using this model across other country pairs to promote binational collaboration., (© 2023. The Author(s).)

Introduction: Arterial vasodilation and hyperdynamic circulation are considered hallmarks of the pathophysiological mechanisms of decompensation in cirrhosis. However, detailed characterization of peripheral, splanchnic, renal, and cardiac hemodynamic have not previously been published in a spectrum from healthy stage to advanced decompensated liver disease with hepatorenal syndrome-acute kidney injury (HRS-AKI)., Methods: We included 87 patients with cirrhosis and 27 healthy controls in this prospective cohort study. The population comprised patients with compensated cirrhosis (n = 27) and decompensated cirrhosis (n = 60); patients with decompensated cirrhosis were further separated into subsets of responsive ascites (33), refractory ascites (n = 16), and HRS-AKI (n = 11). We measured portal pressure and assessed regional blood flow by magnetic resonance imaging., Results: Patients with compensated cirrhosis experienced higher azygos venous flow and higher hepatic artery flow fraction of cardiac index than controls ( P &lt; 0.01), but other flow parameters were not significantly different. Patients with decompensated cirrhosis experienced significantly higher cardiac index ( P &lt; 0.01), higher superior mesenteric artery flow ( P = 0.01), and lower systemic vascular resistance ( P &lt; 0.001) compared with patients with compensated cirrhosis. Patients with HRS-AKI had the highest cardiac output and lowest renal flow of all groups ( P &lt; 0.01 and P = 0.02, respectively). Associations of single hemodynamic parameters were stronger with model for end-stage liver disease than with portal pressure., Discussion: The regional cardiocirculatory changes seem closely linked to clinical symptoms with 3 distinguished hemodynamic stages from compensated to decompensated cirrhosis and, finally, to HRS-AKI. The attenuated renal perfusion despite high cardiac output in patients with HRS-AKI challenges the prevailing pathophysiological hypothesis of cardiac dysfunction as a causal factor in HRS-AKI. Finally, magnetic resonance imaging seems an accurate and reliable noninvasive method to assess hemodynamics and has potential as a diagnostic tool in patients with cirrhosis., (Copyright © 2022 by The American College of Gastroenterology.)

Aims: Patients with cirrhosis and portal hypertension are at high risk of developing complications such as variceal hemorrhage, ascites, and cardiac dysfunction, the latter of which is known as cirrhotic cardiomyopathy. Since non-selective beta-blockers (NSBB) may aggravate hemodynamic complications we investigated the effect of real-time propranolol infusion on cardiac function in patients with varying degrees of cirrhosis., Methods: Thirty-eight patients with Child-Pugh A (n = 17), B (n = 17) and C (n = 4) underwent liver vein catheterization and cardiac magnetic resonance imaging. We assessed the effect of real-time propranolol infusion on the hepatic venous pressure gradient, cardiac index, stroke volume, ejection fraction, heart rate, and contractility., Results: Nineteen patients were classified as responders to beta-blocker therapy. In pooling Child-Pugh B and C patients, the reduction in cardiac index by beta-blockade was weaker than in Child-Pugh A patients (-8.5% vs. -20.5%, p = 0.043). The effect of NSBB on portal pressure was inversely correlated to changes in the left atrium where the left atrial volume changed by 4 mL±18 in responders compared to 15 mL±11 in non-responders (p = 0.03). Finally, the baseline ejection fraction correlated inversely with the reduction in portal pressure (r = -0.39, p = 0.02)., Conclusion: We found the effect of beta-blockade on cardiac index in patients with advanced cirrhosis to be less potent than in patients with early cirrhosis, indicating that underlying cirrhotic cardiomyopathy increases, and the cardiac compensatory reserve becomes more compromised, with disease progression. The differential effects of beta-blockade in the left atrium may be used to predict the effect of beta-blockers on portal pressure, but further studies are needed to investigate this possibility., Competing Interests: The authors have declared that no competing interests exist.

Aim: The aim of this study was to obtain insights from patients and their family members on how families are living with atrial fibrillation., Background: Atrial fibrillation is the most common cardiac arrhythmia and is often described as an emerging global epidemic affecting an estimated 33.5 million people worldwide. Living with atrial fibrillation not only affects the patient but also may negatively influence family members' perceived health. The perspective of the family has previously been understudied, and more knowledge on how patients and their family members cope and adjust to life with atrial fibrillation may be helpful when developing future support for patients and their family members when coping with atrial fibrillation., Methods: A qualitative phenomenological study with an inductive, descriptive research approach based on Giorgi's descriptive method was used. Data were gathered through 12 dyadic family interviews. The COnsolidated criteria for REporting Qualitative research checklist was followed while conducting the study., Results: Three major themes emerged: emotional differences , changes in family life, and uncertainty about the future . Atrial fibrillation had multiple effects on the family. Frequently, several adjustments and adaptations had to be made to accommodate life with atrial fibrillation., Conclusion: Patients with atrial fibrillation and their family members feel a need to talk about their emotions and worries. They required support and guidance to manage the challenges of living with atrial fibrillation. These results will be used in a family-focused intervention designed to support families in adjusting and managing their everyday lives with atrial fibrillation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Stine Rosenstrøm et al.)

Background: We have recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in 23 medicated patients with Parkinson's disease (PD) compared to 23 age- and sex-matched healthy controls., Objective: To investigate in a sub-sample of the original cohort whether the observed blood flow response in SMA after oral food intake is related to a delay in gastric emptying., Methods: We studied 15 patients with PD in an "ON-medication" state with a mean disease duration of 3.9 ± 2.2 years and 15 healthy age- and sex-matched individuals. Participants underwent dynamic gastric scintigraphy 0, 30, 60, 120, 180 and 240 minutes after the intake of a standardized radiolabeled test meal. Gastric emptying was compared between groups. 14 of the 15 PD patients and 12 of the 15 healthy control subjects had previously undergone serial postprandial PC-MRI measurements. In these individuals, we tested for a relationship between gastric emptying and postprandial blood flow response in the SMA., Results: The dynamics of gastric emptying did not differ between groups ( p = 0.68). There was substantial inter-subject variability of gastric emptying in PD patients and healthy participants. Only a single PD patient had delayed gastric emptying. In those participants who had undergone PC-MRI, postprandial increase in SMA blood flow was attenuated in PD compared to healthy controls as reported previously ( p = 0.006). Gastric emptying did not correlate with the timing and amplitude of postprandial blood flow increase in SMA., Conclusion: Our preliminary results, obtained in a small group of early-stage PD patients who continued their usual dopamine replacement therapy, suggest that variations in gastric emptying after solid meal intake is within the normal range in the majority of cases. There is also no evidence for a tight relationship between the attenuated postprandial blood flow response in the SMA and normal variations in gastric emptying., Competing Interests: HS has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, the Netherlands and has received royalties as book editor from Springer Publishers, Stuttgart, Germany and from Gyldendal Publishers, Copenhagen, Denmark. FB has received honoraria as a consultant for Ferring Pharmaceuticals, Denmark. AL has received honoraria as speaker from AbbVie, United States. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Siebner, Fuglsang, Madelung, Løkkegaard, Bendtsen, Hove, Damgaard, Madsen and Siebner.)

Background The optimal timing of invasive examination and treatment of high-risk patients with non-ST-segment-elevation acute coronary syndrome has not been established. We investigated the efficacy of early invasive coronary angiography compared with standard-care invasive coronary angiography on the risk of all-cause mortality according to the GRACE (Global Registry of Acute Coronary Events) risk score in a predefined subgroup analysis of the VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) trial. Methods and Results Patients with clinical suspicion of non-ST-segment-elevation acute coronary syndrome with ECG changes indicating new ischemia and/or elevated troponin, in whom invasive coronary angiography was clinically indicated and deemed logistically feasible within 12 hours, were eligible for inclusion. Patients were randomized 1:1 to an early (≤12 hours) or standard (48-72 hours) invasive strategy. The primary outcome of the present study was all-cause mortality. Of 2147 patients randomized in the VERDICT trial, 2092 patients had an available GRACE risk score. Of these, 1021 (48.8%) patients had a GRACE score >140. During a median follow-up of 4.1 years, 192 (18.8%) and 54 (5.0%) patients died in the high and low GRACE score groups, respectively. The risk of death with the early invasive strategy was increased in patients with a GRACE score ≤140 (hazard ratio [HR], 2.04 [95% CI, 1.16-3.59]), whereas there was a trend toward a decreased risk of death with the early invasive strategy in patients with a GRACE score >140 (HR, 0.83 [95% CI, 0.63-1.10]) ( P interaction =0.006). Conclusions In patients with non-ST-segment-elevation acute coronary syndrome, we found a significant interaction between timing of invasive coronary angiography and GRACE score on the risk of death. Randomized clinical trials are warranted to establish the efficacy and safety among high-risk and low-risk patients with non-ST-segment-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02061891.

Background: MR elastography can determine organ-related stiffness, which reflects the degree of fibrosis. Liver stiffness increases in cirrhosis, and stiffness increases further post-prandially due to increased portal blood in-flow. Non-selective beta-blockers (NSBB) reduce the portal venous inflow, but their effect on liver and spleen stiffness are disputed., Aims: To assess whether MR elastography of the liver or spleen reflects the severity of cirrhosis, whether treatment with NSBB changes liver and spleen stiffness and whether changes in stiffness can predict the effect of NSBB on portal pressure., Methods: Fifty-two patients with cirrhosis underwent liver vein catheterization and two-dimensional (2D) MR elastography on separate days. Thirty-six of the patients had a hepatic venous pressure gradient (HVPG) of ≥12 mmHg and were tested prior to, and after, intravenous infusion of NSBB using HVPG measurement and MR elastography., Results: HVPG showed a strong, positive, linear relationship with liver stiffness (r 2  = 0.92; P < .001) and spleen stiffness (r 2  = 0.94; P < .001). The cut-off points for identifying patients with a HVPG ≥ 12 mmHg were 7.7 kPa for liver stiffness (sensitivity 0.78, specificity 0.64) and 10.5 kPa for spleen stiffness (sensitivity 0.8, specificity 0.79). Intravenous administration of NSBB significantly decreased spleen stiffness by 6.9% (CI: 3.5-10.4, P < .001), but NSBB had no consistent effect on liver stiffness. However, changes in spleen stiffness were not related to the HVPG response (P = .75)., Conclusions: Two-dimensional MR elastographic estimation of liver or spleen stiffness reflects the degree of portal hypertension in patients with liver cirrhosis, but changes in stiffness after NSBB do not predict the effect on HVPG., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS., Methods and Analysis: FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the primary endpoint of cumulative number of diagnostic tests and a safety endpoint (MACE). Angina symptoms, quality of life and risk factor modification will be assessed with questionnaires at baseline, 3 months and 12 months after randomisation. The study is powered to detect superiority in terms of a reduction of ≥15% in the primary endpoint between the two groups with a power of 80%, and non-inferiority on the secondary endpoint with a power of 90%. The significance level is 0.05. The non-inferiority margin is set to 1.5%. Randomisation began on October 2019. Follow-up is planned to be completed by December 2022., Ethics and Dissemination: This study has been approved by the Danish Medical Agency (2019024326), Danish National Committee on Health Research Ethics (H-19012579) and Swedish Ethical Review Authority (Dnr 2019-04252). All patients participating in the study will sign an informed consent. All study results will be attempted to be published as soon as possible., Trial Registration Number: NCT04121949; Pre-results., Competing Interests: Competing interests: LHB, KWH, JB-S, HE, SAH-P, MH, JDH, MK, MTJ, SR, SS, SG and EP: None. TB-S: Steering Committee member of the Amgen financed GALACTIC-HF trial; Advisory Board: Sanofi Pasteur; Advisory Board: Amgen; Speaker Honorarium: Novartis; Speaker Honorarium: Sanofi Pasteur; Research grant: GE Healthcare; Research grant: Sanofi Pasteur. DE: Advisory board for Acarix A/S., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Nonalcoholic fatty liver disease (NAFLD) denotes a condition with excess fat in the liver. The prevalence of NAFLD is increasing, averaging > 25% of the Western population. In 25% of the patients, NAFLD progresses to its more severe form: nonalcoholic steatohepatitis and >25% of these progress to cirrhosis following activation of inflammatory and fibrotic processes. NAFLD is associated with obesity, type 2 diabetes, and the metabolic syndrome and represents a considerable and increasing health burden. In the near future, NAFLD cirrhosis is expected to be the most common cause for liver transplantation. NAFLD patients have an increased risk of developing cardiovascular disease as well as liver-related morbidity. In addition, hepatic steatosis itself appears to represent an independent cardiovascular risk factor. In the present review, we provide an overview of the overlapping mechanisms and prevalence of NAFLD and cardiovascular disease., Competing Interests: Dr. Kimer reports grants from Novo Nordisk Foundation, outside the submitted work., (Thieme. All rights reserved.)

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Patients with AF often experience debilitating symptoms, stress and reduced health-related quality of life. Previous qualitative research on AF has primarily focused on the patient. AF, however, can also be burdensome for the patient's family., Aim: The aim of this study was to explore how family members experience life when a close member in the family has AF., Method: Transcribed focus group interviews were analysed using content analysis approach inspired by Graneheim and Lundman., Results: Two focus group interviews were conducted with 11 family members. The overall theme was Dancing with AF. The theme emerged from three categories: 1) Handling AF as a living condition, 2) Influencing the roles of family members, 3) Fear of AF attack. AF had a very significant impact on the patients' family members, forcing them to reconstruct their daily lives., Conclusions: AF has multiple consequences for family members and can give rise to conflicts concerning family roles. Family members have a lack of knowledge of AF and fear of how AF can cause changes in the family members' everyday lives. This study demonstrates that there is a need for further research of ways to support the family members of patients with AF., Competing Interests: The authors have declared that no competing interests exist.

Background: More than half of women with symptoms suggestive of myocardial ischaemia have no obstructive coronary artery disease (CAD), yet they face a higher risk of cardiovascular mortality and morbidity. Both vital exhaustion (VE) and depression have been linked to adverse cardiovascular prognosis in patients with CAD. We aimed to assess whether symptomatic women with no obstructive CAD are more vitally exhausted compared with asymptomatic women. Furthermore, we investigated the overlap between the constructs of VE and depression., Methods: Prevalence and burden of VE was assessed in symptomatic women with no obstructive CAD (n=1.266) and asymptomatic women (n=2.390). Among symptomatic women, we also assessed chest pain characteristics and symptoms of Hospital Anxiety and Depression Questionnaire., Findings: Median (IQR) VE score was 4 (1-9) and 2 (0-5) in symptomatic and asymptomatic women, respectively (age adjusted, p<0.001). The risk of severe VE was significantly higher in symptomatic women compared with asymptomatic women (OR 3.3, 95% CI 2.5 to 4.4), independent of age and risk factors, and was associated with symptom severity. VE and depression scores were correlated but principal component cluster analysis (PCCA) showed clear distinctiveness between the two constructs., Conclusions: Women with chest pain and no obstructive CAD are more vitally exhausted compared with asymptomatic women. PCCA showed that VE is distinct from depression in symptomatic women., Clinical Implications: Mental health screening focusing on depressive symptomatology in women with chest pain presenting with symptoms of mental and physical exhaustion may overlook VE in these patients., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS)., Objectives: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS., Methods: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure., Results: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07)., Conclusions: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891)., Competing Interests: Funding Support and Author Disclosures This study was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research (grant 09–066994) and the Research Council of Rigshospitalet, Copenhagen, Denmark. Dr. Kofoed has received grants from the Danish Research Foundation during the conduct of the study, in addition to grants from the Research Council of Rigshospitalet, AP Moller og Hustru Chastine McKinney Mollers Fond, the Danish Heart Foundation, and Canon Medical Corporation, outside the submitted work. Dr. Engstrom has received personal fees from Abbott, AstraZeneca, Bayer, Boston Scientific, and Novo, outside the submitted work. Dr. Linde has received grants from the Danish Research Foundation and the Research Council of Rigshospitalet during the conduct of the study. Dr. Torp-Pedersen has received grants from Bayer, outside the submitted work. Dr. Abdulla has received personal fees from Novartis Healthcare, outside the submitted work. Dr. Kober has received grants from the Danish Research Foundation during the conduct of the study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Gastrointestinal dysfunction and related clinical symptoms are common in Parkinson's disease (PD), but the underlying mechanisms are still poorly understood., Objective: In this study, we investigated how PD affects the postprandial vascular response in the splanchnic circulation., Methods: 23 patients with PD in the "ON-medication" state and 23 age- and sex-matched healthy control participants underwent serial phase-contrast magnetic resonance imaging (PC-MRI) to measure the postprandial blood flow response in the superior mesenteric artery (SMA). Participants ingested a standardized liquid test meal (∼400 kcal) and underwent four PC-MRI runs within the following hour. Each PC-MRI run consisted of six consecutive measurements of SMA blood flow., Results: In both groups, standardized food intake triggered an increase of blood flow in the SMA, but absolute and relative increases in blood flow were attenuated in patients compared to the control group (p < 0.001). While baseline blood flow in the SMA was comparable in both groups, the postprandial maximum blood flow was attenuated in patients (p = 0.03). The temporal dynamics of the postprandial blood flow did not differ between groups. Postprandial SMA blood flow increase in patients correlated neither with subjective reports of non-motor symptoms or upper gastrointestinal complaints, nor with levodopa equivalent daily dose or disease duration. Blood glucose measurements in between the PC-MRI runs showed a smaller postprandial increase in blood glucose in the patient group (p = 0.006)., Conclusion: This study provides first-time evidence that patients with PD have an attenuated postprandial blood flow response in the SMA, indicating an impaired functional regulation of gastrointestinal perfusion in response to food intake in PD.

Background: A significant number of women with angina and no obstructive coronary artery disease (CAD; <50% stenosis) have coronary microvascular dysfunction (CMD) which carries an adverse cardiovascular prognosis. Coronary microvascular function can be evaluated by transthoracic Doppler echocardiography (TTDE) as a coronary flow velocity reserve (CFVR) and by static CT myocardial perfusion (CTP) as a myocardial perfusion reserve (MPR). Whether these methods are correlated is not known. We assessed the correlation between CFVR and MPR and investigated whether women with angina, CMD and no obstructive CAD have reduced MPR compared with asymptomatic women., Methods: Static CTP with adenosine-induced vasodilation and TTDE of the left anterior descending artery with dipyridamole-induced vasodilation were successfully performed and analysed in 99 women with stable angina and no obstructive CAD and 33 asymptomatic women with no obstructive CAD. CMD was defined as CFVR < 2., Results: Correlation between rate-pressure product corrected MPR and CFVR was weak but significant (r = .23; p = .007). MPR was highest among asymptomatic women with normal CFVR (median [interquartile range; IQR] 158 [145-181] %). Symptomatic women with normal CFVR had reduced MPR (148 [134-162] %; age-adjusted p < .001); however, the lowest MPR was found in symptomatic women with CMD (140 [129-164] %; age-adjusted p < .001), independent of cardiovascular risk factors and haemodynamic parameters (p = .017)., Conclusion: Women with angina, CMD and no obstructive CAD had markedly diminished MPR compared with asymptomatic women. Correlation between CFVR and MPR was weak, suggesting that CTP and TTDE are not interchangeable for detection of CMD., (© 2020 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Left atrial enlargement is a known marker of chronic diastolic dysfunction and was recently shown to be an independent predictor of mortality in cirrhosis. Real time 3-dimensional echocardiography (3DE) is an emerging modality that enables accurate measurements of the left atrial (LA) volume and function. Assessment of LA volumes with 3DE has never been applied in cases of cirrhosis. We therefore aimed to investigate LA volumes using the novel 3DE technique in relation to liver dysfunction and outcome in patients with cirrhosis. A prospective study of 47 cirrhotic patients without cardiovascular disease and ten healthy controls. The patients underwent clinical evaluation, blood sampling, liver vein catheterization, ECG and tissue Doppler echocardiography, including 3DE. Patients were followed up for a median of 25 months with registration of death and liver transplantation (LT). 3DE-derived maximal left atrial volume index (LAVI max ) and minimal left atrial volume index (LAVI min ) were higher in patients with a Child Pugh score of 8 or higher than in patients with a score lower than 8 (30.0 vs. 22.3 mL/m 2 , P=0.008 and 14.6 vs. 9.5 mL/m 2 , P=0.04, respectively). LA volumes correlated with model for end-stage liver disease (MELD) score (r=0.40, P=0.005), hepatic venous pressure gradient (r=0.34, P=0.04), and biochemical markers of advanced liver disease. Twelve patients experienced the composite end-point of death or LT during follow-up and these patients had increased LA volumes with a higher LAVI max (34.3±14.8 vs. 25.9±7.3 mL/m 2 , P=0.01) and a higher LAVI min (16.3±7.3 vs. 10.8±5.1 mL/m 2 , P=0.007). Patients with advanced cirrhosis have increased minimal and maximal left atrial volumes, which correlate with the degree of the liver dysfunction and poor prognosis.

Background: Fibrogenesis and inflammation contribute to the progression of cirrhosis. However, it is unknown if these processes also contribute to the development of cirrhotic cardiomyopathy (CCM). Novel magnetic resonance imaging with quantification of the extracellular volume (ECV) provides an estimate of the fibrotic remodelling in the liver and heart., Aim: To investigate the relationship between liver and cardiac ECV in cirrhosis and their association with collagen turnover and inflammation., Methods: A prospective study of 52 patients with cirrhosis and 14 healthy controls. All patients underwent contrast-enhanced MRI with T1-mapping and quantification of myocardial and liver ECV, biochemical assessments of collagen turnover (PRO-C3, PRO-C5, PRO-C6, collagen type IV degradation fragment, collagen type V degradation fragment, LG1M) and inflammation (TNFα, IL-1β, IL-6, IL-8, IL-18, SDF1α, sCD163, sMR, soluble macrophage mannose receptor)., Results: Myocardial and liver ECV were increased in patients compared with healthy controls (myocardial ECV 31.2 ± 5.5% vs 27.4 ± 2.9%, P = 0.037; liver ECV 44.1 ± 9.6% vs 33.7 ± 6.7%, P < 0.001). Myocardial ECV correlated strongly with liver ECV (r = 0.48, P = 0.001) and biomarkers of collagen formation and inflammation (P < 0.005). Similarly, liver ECV correlated with biomarkers of collagen formation and inflammation (P < 0.003). In a multivariate analysis, liver ECV was predicted by biomarkers of collagen formation (PRO-C3 and PRO-C6), whereas myocardial ECV was predicted by biomarkers of collagen formation (PRO-C6) and inflammation (IL-6 and sMR)., Conclusion: Structural myocardial changes seem closely related to liver fibrosis in patients with cirrhosis. The strong associations with biomarkers of collagen formation and inflammation provide new insight into the role of inflammation and fibrogenesis in the development of structural cardiac abnormalities, potentially leading to CCM., (© 2020 John Wiley & Sons Ltd.)