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Background: Biomarkers are used for long-term risk prediction of cardiovascular (CV) events in patients presenting with suspected acute coronary syndromes., Objectives: This study investigated whether there are sex differences in the long-term prognostic value of biomarkers in patients presenting with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS)., Methods: High-sensitivity cardiac troponin (hs-cTn), hs-cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, and C-reactive protein (CRP) concentrations were measured in 1,476 patients admitted with suspected NSTE-ACS. Patients were followed up for a median of 1,547 (IQR: 873-1,842) days until a primary composite endpoint of all-cause mortality, incident myocardial infarction, or heart failure hospitalization. A secondary endpoint of CV death was also registered., Results: For the primary endpoint, a log2 increase of hs-cTn and hs-cTnI concentration was associated with a higher adjusted hazard ratio in women (hs-cTn: 1.3, 95% CI: 1.2-1.5; hs-cTnI: 1.2, 95% CI: 1.1-1.2) than in men (hs-cTn: 1.1, 95% CI: 1.0-1.2; hs-cTnI: 1.0, 95% CI: 1.0-1.1); P value for interaction with sex: 0.009 (hs-cTn) and 0.005 (hs-cTnI). A similar interaction was shown for NT-proBNP (P for interaction: 0.043). GDF-15 and CRP were independent predictors of the primary endpoint, but the interaction by sex was nonsignificant., Conclusions: In contrast to CRP and GDF-15, increasing concentrations of hs-cTn, hs-cTnI, and NT-proBNP are associated with higher risk of death and CV events in female than in male patients presenting with suspected NSTE-ACS. Sex-adjustment of hs-cTn and NT-proBNP may increase the accuracy of long-term CV prognostication in women and men., Competing Interests: Funding Support and Author Disclosures This study was financed by a grant from the Western Norway Regional Health Authority (grant number: 912265). Dr G.M.S. Myrmel has had a part time research grant from Trond Mohn Foundation and currently is receiving a Ph.D. grant from the Western Norway Regional Health Authority (grant number: F-12589). The reagent costs for GDF-15 were covered by Roche Diagnostics. The sponsor had no influence on the analyzing or interpretation of the data, nor on the writing of the manuscript. Dr Aakre has served on the advisory board of Roche Diagnostics, Siemens Healthineers, and SpinChip; consultant honoraria from CardiNor; lecturing honorarium from Siemens Healthineers, Roche Diagnostics, Mindray, and Snibe Diagnostics; and research grants from Siemens Healthineers and Roche Diagnostics. She is an Associate Editor of Clinical Biochemistry and Chair of the IFCC Committee of Clinical Application of Cardiac Bio-markers. Dr Omland has received speaker and/or consultancy honoraria from Abbott Diagnostics, Bayer, CardiNor, Roche Diagnostics, and Siemens Healthineers and has received research support from Abbott Diagnostics, Novartis, Roche Diagnostics, via Akershus University Hospital. Dr Skadberg has received lecture fees from Abbott Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Annually, approximately 7.6 million individuals experience a new ischemic stroke, and roughly 25% of all ischemic strokes are cardiogenic in origin, carrying a high risk of recurrence, death and disability. To prevent future ischemic strokes, especially in younger individuals, it is crucial to detect and treat direct and indirect cardioembolic sources., Summary: Cardiac imaging is a rapidly evolving field, and post-stroke cardiac imaging is no longer limited to echocardiography, but also includes other imaging techniques, such as cardiac magnetic resonance imaging and cardiac computed tomography. Clinicians must be familiar with numerous cardiac and systemic disorders related to stroke and consider the possibilities that imaging diagnostics have to offer. Additional diagnostics tests, such as pre- and transcranial ultrasound with a bubble test, can also increase the diagnostic accuracy for detecting right-left shunt embolisms. Moreover, a patent foramen ovale (PFO) has traditionally been indicated as a minor or uncertain risk factor for ischemic stroke. However, PFO-associated strokes are a distinct category among the cardioembolic sources as in most cases we do not assume that the thrombus has been developed in-situ in the PFO-structure or elsewhere intracardial, but that PFO merely is acting as a mediator for a paradoxical, venous embolism. The article has two parts: Part I, the heart-brain axis, describes multimodality cardiac imaging in the assessment of cardioembolic sources of ischemic stroke, with a special focus on disorders that traditionally have received little attention in the literature. Part II discusses the brain-heart axis, namely when acute cerebrovascular events lead to cardiac dysfunction, for example neurogenic stunned myocardium and Takotsubo syndrome., Key Messages: Advances in cardiovascular imaging have significantly enhanced the detection of cardiac disorders associated with stroke. Clinicians involved in post stroke work-up need to be aware of the capabilities of different imaging modalities for higher individual diagnostic accuracy in order to effectively treat and prevent stroke recurrence., (The Author(s). Published by S. Karger AG, Basel.)

Over the last 30 years, the widespread use of cardiac biomarkers has transformed the diagnostic evaluation of patients with coronary heart disease. Cardiac troponin is integral to the definition of acute myocardial infarction. High-sensitivity cardiac troponin (hs-cTn) assays can improve risk stratification to facilitate both the rapid rule out of myocardial infarction and prediction of future cardiovascular events. Numerous circulating biomarkers representing different pathological pathways improve prediction of atherosclerotic cardiovascular disease (ACVD) and coronary artery disease (CAD). In parallel, coronary computed tomography angiography (CCTA) has become the most widely used imaging modality for the evaluation of patients with possible angina. CCTA now allows for the quantification of coronary calcification, atherosclerotic plaque volume and different plaque characteristics, enabling the identification high-risk features and inflammation. In the future, the use of CCTA is likely to extend to risk stratification for the prevention of ACVD. As such, how to integrate these diagnostic and prognostic circulating and imaging biomarkers is a topic of considerable interest. This review aims to describe current status and future possibilities for the integration of CCTA and cardiac biomarker testing to improve the identification and treatment of individuals with coronary heart disease and heightened cardiovascular risk., Competing Interests: Declaration of Competing Interest The authors 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Growth differentiation factor-15 (GDF-15) is a predictor of death and cardiovascular events when measured during index hospitalisation in patients with acute chest pain. This study investigated the prognostic utility of measuring GDF-15 3 months after an admission with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS)., Methods: GDF-15 was measured at baseline and 3 months after admission in 758 patients admitted with suspected NSTE-ACS. Patients were followed for a median of 1540 (IQR: 1087-1776) days after the 3-month visit. The primary endpoint was all-cause mortality, while the secondary composite endpoint included all-cause mortality, incident myocardial infarction and heart failure hospitalisation during follow-up., Results: In patients with GDF-15 ≥1200 pg/mL (n=248), 18% died and 25% met the composite endpoint. In patients with GDF-15 <1200 pg/mL (n=510), 1.7% died and 4% met the composite endpoint. The GDF-15 concentration (log2 transformed) at 3 months was significantly associated with all-cause mortality (adjusted HR: 2.2, 95% CI: 1.4 to 3.3, p<0.001) and the composite endpoint (adjusted HR: 1.9, 95% CI: 1.4 to 2.7, p<0.001), independently of traditional risk factors and baseline troponin T. A 10% change in GDF-15 concentration from baseline to the 3-month visit was associated with increased risk of all-cause mortality (HR: 1.06, 95% CI: 1.01 to 1.13, p=0.031), adjusting for baseline GDF-15 concentrations., Conclusions: High GDF-15 concentrations 3 months after admission for suspected NSTE-ACS are associated with long-term mortality and cardiovascular events, independent of traditional risk factors and troponin T. A change in GDF-15 concentration can provide prognostic information., Competing Interests: Competing interests: KMA has served on advisory board for Roche Diagnostics and SpinChip, consultant honoraria from CardiNor, lecturing honorarium from Siemens Healthineers and Snibe Diagnostics, and research grants from Siemens Healthineers and Roche Diagnostics. She is the Associate Editor of Clinical Biochemistry and Chair of the IFCC Committee of Clinical Application of Cardiac Bio-markers. TO has received speaker and/or consultancy honoraria from Abbott Diagnostics, Bayer, CardiNor, Roche Diagnostics and Siemens Healthineers, and has received research support from Abbott Diagnostics, Novartis, Roche Diagnostics, via Akershus University Hospital. ØS has received lecture fees from Abbott Diagnostics. GMSM, O-TS, HLT, JL, ROB, VVSB, ØRM and KV have no disclosures., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Giant cell myocarditis (GCM) is a rare, probably underdiagnosed and potentially fatal disease in young and middle-aged patients. Disease progression is often rapid, and life-threatening arrhythmias and cardiogenic shock due to progressive left ventricular failure are among the most feared complications. Although cardiac biomarkers and multimodality imaging are used as initial diagnostic tests in most patients, endomyocardial biopsy (EMB) is often required for a definitive diagnosis. However, there are still gaps in our knowledge in terms of the etiology, early diagnosis, management and prognosis of GCM., Case Description: We present the case of a male patient in his early 50s admitted to Haukeland University Hospital with fulminant GCM. He had no significant medical history in the past apart from hypertension, and presented to hospital in cardiogenic shock after a few weeks of progressive shortness of breath. Rapid initiation of methylprednisolone had an immediate effect on reducing myocardial inflammation, and sustained treatment with a combination of immunosuppressive agents along with optimal heart failure medications led to complete recovery of the heart function and clinical remission over several years. The case study highlights the urgency of an early EMB, access to mechanical circulatory support (MCS) and the efficacy of immunosuppressive treatment and optimal medical management for heart failure. Finally, our review of the literature also provides an updated guidance on the contemporary management of GCM patients., Conclusions: Accurate and early diagnosis with EMB in patients with GCM are crucial for better outcomes. Rapid initiation of methylprednisolone reduces myocardial inflammation and the risk of death. Sustained treatment with a combination of immunosuppressive agents together with optimal heart failure medications are essential for myocardial recovery and long-term stabilization. The use of MCS is the cornerstone in the management of GCM with a clear survival benefit., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-23-265/coif). The authors have no conflicts of interest to declare., (2023 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background: Acute chest pain is associated with an increased risk of death and cardiovascular events even when acute myocardial infarction (AMI) has been excluded. Growth differentiation factor-15 (GDF-15) is a strong prognostic marker in patients with acute chest pain and AMI, but the prognostic value in patients without AMI is uncertain. This study sought to investigate the ability of GDF-15 to predict long-term prognosis in patients presenting with acute chest pain without AMI., Methods: In total, 1320 patients admitted with acute chest pain without AMI were followed for a median of 1523 days (range: 4 to 2208 days). The primary end point was all-cause mortality. Secondary end points included cardiovascular (CV) death, future AMI, heart failure hospitalization, and new-onset atrial fibrillation (AF)., Results: Higher concentrations of GDF-15 were associated with increased risk of death from all causes (median concentration in non-survivors vs survivors: 2124 pg/mL vs 852 pg/mL, P < 0.001), and all secondary end points. By multivariable Cox regression, GDF-15 concentration ≥4th quartile (compared to <4th quartile) remained an independent predictor of all-cause death (adjusted hazard ratio (HR): 2.75; 95% CI, 1.69-4.45, P < 0.001), CV death (adjusted HR: 3.74; 95% CI, 1.31-10.63, P = 0.013), and heart failure hospitalization (adjusted HR: 2.60; 95% CI, 1.11-6.06, P = 0.027). Adding GDF-15 to a model consisting of established risk factors and high-sensitivity cardiac troponin T (hs-cTnT) led to a significant increase in C-statistics for prediction of all-cause mortality., Conclusions: Higher concentrations of GDF-15 were associated with increased risk of mortality from all causes and risk of future CV events., (© American Association for Clinical Chemistry 2023.)

Objectives. In patients with asymptomatic moderate or severe aortic stenosis (AS), exercise testing is used for evaluating the need for aortic valve intervention. Expert opinions about the clinical significance and prognostic value of ST segment depression on electrocardiography (ECG) during exercise testing in AS is conflicting and there are no large studies exploring this issue. We aimed to explore the association of ST segment depression >5 mm during exercise treadmill test (ETT) with all-cause mortality, aortic valve replacement (AVR) or cardiac-related hospitalization. Design. We performed a retrospective analysis of prospectively collected data of a total of 315 patients (mean age 65 ± 12 years, 67% men) with asymptomatic moderate ( n  = 209; 66%) or severe ( n  = 106; 34%) AS. All patients underwent clinical evaluation, echocardiography and ETT. Results. During a mean follow-up of 34.9 ± 34.6 months, 29 (9%) patients died and 235 (74%) underwent AVR. The prevalence of ST segment depression (>5 mm) was 13% ( n  = 41) in the total study population and was comparable in patients with revealed symptoms (17.6%, n  = 16) versus without revealed symptoms (11.3%, n  = 25; p  = .132). ST segment depression on ETT was strongly associated with aortic valve area. In univariate Cox regression analysis, ST segment depression was not associated with cardiac related hospitalizations (HR 1.65; 95% CI 0.89-3.10, p  = .113), all-cause mortality (HR 1.37; 95% CI 0.47-3.98, p  = .564) or AVR (HR 1.30; 95% CI 0.89-1.91, p  = .170). Conclusion. In patients with moderate or severe AS, ST segment depression during ETT is non-specific, carries no prognostic risk and should be used with caution in the clinical interpretation of exercise test.

Severe hypertension has numerous etiologies. When accompanied by bradycardia, the spectrum of differential diagnoses is greatly narrowed and is commonly seen in patients with increased intracranial pressure. However, other etiologies such as bradycardia-induced hypertension are rarely mentioned. Here we report the case of a 73-year-old woman presenting with symptoms of heart failure, severe hypertension, and bradycardia with a 2:1 atrioventricular block. Echocardiography demonstrated increased left ventricular filling secondary to bradycardia and prolonged diastole, leading to greater ventricular stretch, increased contractile force and greater stroke volume (Frank-Starling mechanism), which subsequently caused elevated systolic blood pressure (BP), low diastolic BP and a wide pulse pressure. Treating the bradycardia by pacing led to an immediate and substantial BP reduction, although complete BP normalization had a slower time course and was probably due to the concomitant effect of the antihypertensive treatment initiation. This pathophysiological mechanism has received little attention in the literature. Further, stimulation of sympathetic afferents located in the heart by distension of the cardiac walls as well as the role of vagally innervated cardiopulmonary receptors due to the increased pressure in the heart and the pulmonary artery should also be kept in mind as alternative hypotheses., Competing Interests: There are no conflicts of interest for any authors., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Competing Interests: Conflict of Interest: None.