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BACKGROUND: Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding. METHODS: In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban. The primary efficacy objective was to determine whether asundexian is at least noninferior to apixaban for the prevention of stroke or systemic embolism. The primary safety objective was to determine whether asundexian is superior to apixaban with respect to major bleeding events. RESULTS: A total of 14,810 randomly assigned patients were included in the intention-to-treat population. The mean (±SD) age of the patients was 73.9±7.7 years, 35.2% were women, 18.6% had chronic kidney disease, 18.2% had a previous stroke or transient ischemic attack, 16.8% had received oral anticoagulants for no more than 6 weeks, and the mean CHA2DS2-VASc score (range, 0 to 9, with higher scores indicating a greater risk of stroke) was 4.3±1.3. The trial was stopped prematurely at the recommendation of the independent data monitoring committee. Stroke or systemic embolism occurred in 98 patients (1.3%) assigned to receive asundexian and in 26 (0.4%) assigned to receive apixaban (hazard ratio, 3.79; 95% confidence interval [CI], 2.46 to 5.83). Major bleeding occurred in 17 patients (0.2%) who received asundexian and in 53 (0.7%) who received apixaban (hazard ratio, 0.32; 95% CI, 0.18 to 0.55). The incidence of any adverse event appeared to be similar in the two groups. CONCLUSIONS: Among patients with atrial fibrillation at risk for stroke, treatment with asundexian at a dose of 50 mg once daily was associated with a higher incidence of stroke or systemic embolism than treatment with apixaban in the period before the trial was stopped prematurely. There were fewer major bleeding events with asundexian than with apixaban during this time. (Funded by Bayer; OCEANIC-AF ClinicalTrials.gov number, NCT05643573; EudraCT number, 2022-000758-28.).
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Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischemia, various classifications have emerged over time, often with conflicting terminology-eg, "stable coronary artery disease" (CAD), "stable ischemic heart disease," and "chronic coronary syndromes" (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with "acute coronary syndromes" (ACS), the 2023 American guidelines endorsed the alternative term "chronic coronary disease." An unintended consequence of these competing classifications is perpetuation of the restrictive terms "coronary" and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of "acute myocardial ischemic syndromes" and "non-acute myocardial ischemic syndromes," which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischemia, and infarction.
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Multivessel coronary artery disease is present in â¼50% of patients with acute coronary syndrome and, compared with single-vessel disease, entails a higher risk of new ischaemic events and a worse prognosis. Randomized controlled trials have shown the superiority of 'complete revascularization' over culprit lesion-only treatment. Trials, however, only included patients treated with percutaneous coronary intervention (PCI), and evidence regarding complete revascularization with coronary artery bypass graft (CABG) surgery after culprit lesion-only PCI ('hybrid revascularization') is lacking. The CABG after PCI is an open, non-negligible therapeutic option, for patients with non-culprit left main and/or left anterior descending coronary artery disease where evidence in chronic coronary syndrome patients points in several cases to a preference of CABG over PCI. This valuable but poorly studied 'PCI first-CABG later' option presents, however, relevant challenges, mostly in the need of interrupting post-stenting dual antiplatelet therapy (DAPT) for surgery to prevent excess bleeding. Depending on patients' clinical characteristics and coronary anatomical features, either deferring surgery after a safe interruption of DAPT or bridging DAPT interruption with intravenous short-acting antithrombotic agents appears to be a suitable option. Off-pump minimally invasive surgical revascularization, associated with less operative bleeding than open-chest surgery, may be an adjunctive strategy when revascularization cannot be safely deferred and DAPT is not interrupted. Here, the rationale, patient selection, optimal timing, and adjunctive strategies are reviewed for an ideal approach to hybrid revascularization in post-acute coronary syndrome patients to support physicians' choices in a case-by-case patient-tailored approach.
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Aspirin has been known for a long time and currently stays as a cornerstone of antithrombotic therapy in cardiovascular disease. In patients with either acute or chronic coronary syndromes undergoing percutaneous coronary intervention aspirin is mandatory in a dual antiplatelet therapy regimen for prevention of stent thrombosis and/or new ischaemic events. Aspirin is also currently a first-option antithrombotic therapy after an aortic prosthetic valve replacement and is occasionally required in addition to oral anticoagulants after implantation of a mechanical valve. Presumed or demonstrated aspirin hypersensitivity is a main clinical problem, limiting the use of a life-saving medication. In the general population, aspirin hypersensitivity has a prevalence of 0.6%-2.5% and has a plethora of clinical presentations, ranging from aspirin-exacerbated respiratory disease to anaphylaxis. Although infrequent, when encountered in clinical practice aspirin hypersensitivity poses for cardiologists a clinical dilemma, which should never be trivialized, avoiding-as much as possible-omission of the drug. We here review the epidemiology of aspirin hypersensitivity, provide an outline of pathophysiological mechanisms and clinical presentations, and review management options, starting from a characterization of true aspirin allergy-in contrast to intolerance-to suggestion of desensitization protocols.
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Aspirina , Hipersensibilidad a las Drogas , Humanos , Aspirina/efectos adversos , Hipersensibilidad a las Drogas/epidemiología , Inhibidores de Agregación Plaquetaria/efectos adversos , Desensibilización Inmunológica/métodos , Intervención Coronaria Percutánea/efectos adversos , CardiólogosRESUMEN
Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischaemia, various classifications have emerged over time, often with conflicting terminology-e.g. 'stable coronary artery disease' (CAD), 'stable ischaemic heart disease', and 'chronic coronary syndromes' (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with 'acute coronary syndromes' (ACS), the 2023 American guidelines endorsed the alternative term 'chronic coronary disease'. An unintended consequence of these competing classifications is perpetuation of the restrictive terms 'coronary' and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischaemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of 'acute myocardial ischaemic syndromes' and 'non-acute myocardial ischaemic syndromes', which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST-segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischaemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischaemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischaemia and infarction.
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Pulmonary arterial hypertension (PAH) is a rare and progressive disorder that affects the pulmonary vasculature. Although recent developments in pharmacotherapy have extended the life expectancy of PAH patients, their 5-year survival remains unacceptably low, underscoring the need for multitarget and more comprehensive approaches to managing the disease. This should incorporate not only medical, but also lifestyle interventions, including dietary changes and the use of nutraceutical support. Among these strategies, n-3 polyunsaturated fatty acids (n-3 PUFAs) are emerging as promising agents able to counteract the inflammatory component of PAH. In this narrative review, we aim at analysing the preclinical evidence for the impact of n-3 PUFAs on the pathogenesis and the course of PAH. Although evidence for the role of n-3 PUFAs deficiencies in the development and progression of PAH in humans is limited, preclinical studies suggest that these dietary components may influence several aspects of the pathobiology of PAH. Further clinical research should test the efficacy of n-3 PUFAs on top of approved clinical management. These studies will provide evidence on whether n-3 PUFAs can genuinely serve as a valuable tool to enhance the efficacy of pharmacotherapy in the treatment of PAH.
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Anticoagulants are the cornerstone for prevention and treatment of thrombosis but are not completely effective, and concerns about the risk of bleeding continue to limit their uptake. Animal studies and experience from patients with genetic coagulation factor XI deficiency suggesting that this factor is more important for thrombosis than for haemostasis raises the potential for drugs that target factor XI to provide safer anticoagulation. Multiple factor XI inhibitors are currently under evaluation in clinical trials, including parenterally administered antisense oligonucleotides, monoclonal antibodies, and orally active small-molecule inhibitors. Promising results of phase 2 trials in patients undergoing major orthopaedic surgery, and in those with end-stage kidney disease, atrial fibrillation and acute coronary syndromes have led to large phase 3 trials that are currently ongoing. We here review premises for the use of these agents, results so far accrued, ongoing studies, and perspectives for future patient care.
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Factor XI , Trombosis , Animales , Anticoagulantes/uso terapéutico , Coagulación Sanguínea , Factor XI/genética , Factor XI/farmacología , Factor XI/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Trombosis/prevención & control , Trombosis/tratamiento farmacológico , HumanosRESUMEN
Over the past 20 years, there has been a shift from vitamin K antagonists to direct oral anticoagulants (DOACs), which include the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, edoxaban, and rivaroxaban. Although DOACs are associated with less serious bleeding than vitamin K antagonists, bleeding still occurs with DOACs, particularly in the elderly and in those with comorbidities. Reversal of the anticoagulant effects of the DOACs may be needed in patients with serious bleeding and in those requiring urgent surgery or intervention. Reversal can be effected with specific agents, such as idarucizumab for dabigatran and andexanet alfa for apixaban, edoxaban, and rivaroxaban, or with non-specific agents, such as prothrombin complex concentrates, activated prothrombin complex concentrate, and recombinant activated factor VII. This paper (i) provides an update on when and how to reverse the DOACs, (ii) describes new reversal agents under development, and (iii) provides a strategic framework for the reversal of the factor XI inhibitors currently under investigation in phase three clinical trials.
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Dabigatrán , Rivaroxabán , Humanos , Anciano , Dabigatrán/efectos adversos , Rivaroxabán/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Anticoagulantes/efectos adversos , Inhibidores del Factor Xa/farmacología , Inhibidores del Factor Xa/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Vitamina K , Administración OralRESUMEN
AIMS: Members of the chromogranin family play a role in angiogenesis. One such biologically active peptide, generated through the processing of chromogranin A, is vasostatin-2. This study aimed at assessing the association of serum vasostatin-2 levels with coronary collateral vessels (CCV) in diabetic patients with chronic total occlusions (CTO) and the effects of vasostatin-2 on angiogenesis in diabetic mice with hindlimb or myocardial ischemia. METHODS AND RESULTS: Serum levels of vasostatin-2 in 452 diabetic CTO patients were evaluated. The status of CCV was categorized according to the Rentrop score. Vasostatin-2 recombinant protein or phosphate-buffered saline were then injected intraperitoneally in diabetic mouse models of hindlimb or myocardial ischemia, followed by laser Doppler imaging and molecular biology examinations. The effects of vasostatin-2 were also ascertained in endothelial cells and macrophages, with mechanisms clarified using ribonucleic acid (RNA) sequencing. Serum levels of vasostatin-2 were significantly different and progressively higher across Rentrop score 0, 1, 2, and 3 groups (P < .001), with significantly lower levels in patients with poor CCV (Rentrop score 0 and 1) than in those with good CCV (Rentrop score 2 and 3) (P < .05). Vasostatin-2 significantly promoted angiogenesis in diabetic mice with hindlimb or myocardial ischemia. RNA-seq analyzes verified an angiotensin-converting enzyme 2 (ACE2)-mediated vasostatin-2-induction of angiogenesis in ischemic tissues. CONCLUSION: Lower serum levels of vasostatin-2 are associated with poor CCV in diabetic CTO patients compared with patients with good CCV. Vasostatin-2 significantly promotes angiogenesis in diabetic mice with hindlimb or myocardial ischemia. Such effects are mediated by ACE2.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus Experimental , Isquemia Miocárdica , Ratones , Animales , Cromogranina A/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Células Endoteliales/metabolismo , Diabetes Mellitus Experimental/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Circulación ColateralRESUMEN
BACKGROUND: Tissue levels of n-3 polyunsaturated fatty acids (PUFAs) have been inversely related with risk of myocardial infarction (MI). Whether ratios of n-3 to n-6 PUFAs, reflecting both dietary intake of n-3 PUFAs and competing n-6 PUFAs, are better predictors of future MI than n-3 PUFA fractions is unclear. We aimed at investigating whether such ratios in adipose tissue better predict MI than n-3 PUFA fractions. METHODS: Subcutaneous adipose tissue biopsies were obtained in a random sample (n = 3,500) of the Diet, Cancer and Health cohort (n = 57,053). Adipose tissue content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), arachidonic acid (AA) and linoleic acid was determined using gas chromatography. Fractions of selected n-3 PUFAs and n-3/n-6 PUFA ratios were correlated to the 15-year occurrence of MI in a case-cohort design. RESULTS: A total of 2,406 participants experienced an MI during follow-up. Adipose tissue total marine n-3 PUFAs, EPA+DHA, EPA, EPA/AA, DHA/AA and (EPA + DPA + DHA)/AA were all inversely associated with risk of incident MI. Evaluating the predictive power (Harrel's C-index) of the selected metrics, fractions of marine n-3 PUFAs and ratios of EPA/AA, DHA/AA, (EPA + DHA)/AA and (EPA + DPA + DHA)/AA all refined risk prediction over age and sex alone. At multivariable analyses, however, the above ratios were the only metrics providing additional risk prediction. Differences in ratios were related to differences in food intake. CONCLUSIONS: Both adipose tissue n-3 PUFAs fractions and ratios of n-3 PUFAs/AA were associated with a lower occurrence of MI, but ratios provided superior risk prediction. Dietary strategies affecting n-3/n-6 PUFA ratios should be further investigated for prediction of MI with dietary interventions at the population level and in intervention studies.
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Ácidos Grasos Omega-3 , Infarto del Miocardio , Humanos , Ácidos Grasos , Ácido Eicosapentaenoico , Ácidos Grasos Omega-6 , Ácido Araquidónico , Infarto del Miocardio/epidemiología , Tejido AdiposoRESUMEN
AIMS: Heart failure (HF) is a risk factor for major adverse events in atrial fibrillation (AF). Whether this risk persists on non-vitamin K antagonist oral anticoagulants (NOACs) and varies according to left ventricular ejection fraction (LVEF) is debated. METHODS AND RESULTS: We investigated the relation of HF in the ETNA-AF-Europe registry, a prospective, multicentre, observational study with an overall 4-year follow-up of edoxaban-treated AF patients. We report 2-year follow-up for ischaemic stroke/transient ischaemic attack (TIA)/systemic embolic events (SEE), major bleeding, and mortality. Of the 13 133 patients, 1854 (14.1%) had HF. Left ventricular ejection fraction was available for 82.4% of HF patients and was <40% in 671 (43.9%) and ≥40% in 857 (56.1%). Patients with HF were older, more often men, and had more comorbidities. Annualized event rates (AnERs) of any stroke/SEE were 0.86%/year and 0.67%/year in patients with and without HF. Compared with patients without HF, those with HF also had higher AnERs for major bleeding (1.73%/year vs. 0.86%/year) and all-cause death (8.30%/year vs. 3.17%/year). Multivariate Cox proportional models confirmed HF as a significant predictor of major bleeding [hazard ratio (HR) 1.65, 95% confidence interval (CI): 1.20-2.26] and all-cause death [HF with LVEF <40% (HR 2.42, 95% CI: 1.95-3.00) and HF with LVEF ≥40% (HR 1.80, 95% CI: 1.45-2.23)] but not of ischaemic stroke/TIA/SEE. CONCLUSION: Anticoagulated patients with HF at baseline featured higher rates of major bleeding and all-cause death, requiring optimized management and novel preventive strategies. NOAC treatment was similarly effective in reducing risk of ischaemic events in patients with or without concomitant HF.
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Fibrilación Atrial , Isquemia Encefálica , Embolia , Insuficiencia Cardíaca , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Masculino , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Anticoagulantes/efectos adversos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/prevención & control , Estudios Prospectivos , Volumen Sistólico/fisiología , Administración Oral , Función Ventricular Izquierda , Hemorragia/inducido químicamente , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Sistema de RegistrosRESUMEN
Haemostasis and thrombosis are closely linked, so that any anticoagulant strategy available today that reduces the thrombotic risk inevitably increases the bleeding risk. However, epidemiological and experimental evidence suggests that inhibiting the contact pathway-the first phase of the intrinsic coagulation pathway-and especially factor XI (FXI) achieves the objective of preventing thrombosis with minimal interference on the haemostatic process. Several pharmacological strategies that act by inhibiting FXI are being studied in clinical trials. Specifically, Phase 2 clinical trials in patients undergoing major orthopaedic surgery, end-stage renal disease, atrial fibrillation (AF), and acute coronary syndrome have shown promising results, allowing clinical research to advance into Phase 3 clinical trials. FXI inhibitors will not necessarily replace currently available direct oral anticoagulants: this would appear too ambitious as of today. However, it is possible to hypothesize that FXI inhibitors are a useful addition to our therapeutic armamentarium in contexts where current anticoagulants have failed or have not been adequately tested, as well as in categories of patients who are at a high risk of bleeding even with current direct oral anticoagulants.
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In September 2020, the new Editors of the European Heart Journal (EHJ) wrote the following in their inaugural editorial: "The fundamental mission of the Journal remains the reduction of the global burden of cardiovascular disease. We aspire to advance this aim by worldwide teamwork to communicate practice-changing research, inspire clinical cardiologists, and pursue rigour and transparency in the application of science at the service of human health. The Journal will strive to lead the field in its impact, influence, and reach". After more than one year of experience the Editors hope the cardiological community will agree that they are fulfilling this mission. As stewards of the EHJ, the Editor's primary goal is not solely to achieve a high Impact Factor (which attests to the scientific quality and influence of our publications) but also to elevate the practice of cardiovascular medicine worldwide. Accordingly, various initiatives of the EHJ strive to strengthen further links among Editors, Authors, Reviewers and Readers through a series of coordinated and diverse activities, including webinars, active social media presence, and active participation at congresses worldwide. The Editors are proud to serve one of the most important scientific journals in cardiovascular medicine.
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Ponatinib (PON), a tyrosine kinase inhibitor approved in chronic myeloid leukaemia, has proven cardiovascular toxicity. We assessed mechanisms of sex-related PON-induced cardiotoxicity and identified rescue strategies in a murine model. PON+scrambled siRNA-treated male mice had a higher number of TUNEL-positive cells (%TdT+6.12 ± 0.17), higher percentage of SA-ß-gal-positive senescent cardiac area (%SA-ß-gal 1.41 ± 0.59) and a lower reactivity degree (RD) for the survival marker Bmi1 [Abs (OD) 5000 ± 703] compared to female (%TdT+3.75 ± 0.35; %SA-ß-gal 0.77 ± 0.02; Bmi1 [Abs (OD) 8567 ± 2173]. Proteomics analysis of cardiac tissue showed downstream activation of cell death in PON+siRNA scrambled compared to vehicle or PON+siRNA-Notch1-treated male mice. Upstream analysis showed beta-oestradiol activation, and downstream analysis showed activation of cell survival and inhibition of cell death in PON+scrambled siRNA compared to vehicle or PON+siRNA-Notch1-treated female mice. PON+scrambled siRNA-treated mice also had a downregulation of cardiac actin-more marked in males-and vessel density-more marked in females. Female hearts showed greater cardiac fibrosis than their male counterparts at baseline, with no significant change after PON treatment. PON+siRNA-scrambled mice had less fibrosis than vehicle or PON+siRNA-Notch1-treated mice. The left ventricular systolic dysfunction showed by PON+scrambled siRNA-treated mice (male %EF 28 ± 9; female %EF 36 ± 7) was reversed in both PON+siRNA-Notch1-treated male (%EF 53 ± 9) and female mice (%EF 52 ± 8). We report sex-related differential susceptibility and Notch1 modulation in PON-induced cardiotoxicity. This can help to identify biomarkers and potential mechanisms underlying sex-related differences in PON-induced cardiotoxicity.
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Cardiotoxicidad , Piridazinas , Animales , Cardiotoxicidad/etiología , Modelos Animales de Enfermedad , Femenino , Imidazoles , Masculino , Ratones , Piridazinas/farmacología , ARN Interferente PequeñoRESUMEN
Coronary artery anomalies (CAAs) are a group of congenital conditions characterized by abnormal origin or course of any of the 3 main epicardial coronary arteries. Although CAAs have been identified as a common underlying condition in young athletes with sudden cardiac death, the widespread use of invasive and noninvasive coronary imaging has led to increased recognition of CAAs among adults. CAAS are often discovered as an incidental finding during the diagnostic workup for ischemic heart disease. The clinical correlates and prognostic implication of CAAs remain poorly understood in this context, and guideline-recommended therapeutic choices are supported by a low level of scientific evidence. Several studies have examined whether assessment of CAA-related myocardial ischemia can improve risk stratification in these patients, suggesting that multimodality imaging and functional tests may be key in the management of CAAs. The aim of this review is to outline definitions, classification, and epidemiology of the most relevant CAAs, highlighting recent advances and the potential impact of multimodality evaluation, and to discuss current therapeutic opportunities.
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Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Anomalías de los Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/fisiopatología , Anomalías de los Vasos Coronarios/complicaciones , Anomalías de los Vasos Coronarios/fisiopatología , Vasos Coronarios/fisiopatología , Ecocardiografía/métodos , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/fisiopatología , HumanosRESUMEN
Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure, profoundly differ with respect to clinical indications and procedural aspects. Yet, patients undergoing transcatheter cardiac interventions require antithrombotic therapy before, during, or after the procedure to prevent thromboembolic events. However, these therapies are associated with an increased risk of bleeding complications. To date, challenges and controversies exist regarding balancing the risk of thrombotic and bleeding complications in these patients such that the optimal antithrombotic regimens to adopt in each specific procedure is still unclear. In this review, we summarize current evidence on antithrombotic therapies for device-based transcatheter interventions targeting structural heart disease and emphasize the importance of a tailored approach in these patients.
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Fibrinolíticos/uso terapéutico , Cardiopatías/tratamiento farmacológico , Fibrinolíticos/farmacología , Cardiopatías/cirugía , HumanosRESUMEN
BACKGROUND AND OBJECTIVES: The absence of obstructive coronary artery disease (CAD) in patients with angina is common, but its prognosis is debated. We investigated outcomes of such patients to identify predictors of cardiovascular events. METHODS: We selected 1014 patients with angina, evidence of myocardial ischemia at the electrocardiogram (ECG) exercise test or imaging stress tests, and nonobstructive CAD (absence of lumen diameter reduction ≥50%) at coronary angiography between 1999 and 2015. Note that, 1905 age- and risk factors-matched asymptomatic subjects served as "real-world" comparators. The primary endpoint was the occurrence of all-cause death or myocardial infarction. RESULTS: At 6-years median follow-up (interquartile range, 3-9 years), the primary endpoint occurred in 53 patients (5.5%, 0.92/100 person-years). Besides similar event rates compared with asymptomatic subjects (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.62-1.15, p = 0.28), the index population showed a very heterogeneous prognosis. Patients with nonobstructive CAD (HR 1.85, 95% CI 1.02-3.37, p = 0.04, compared with "normal" coronary arteries) and ischemia at imaging tests (HR 2.11, 95% CI 1.07-4.14, p = 0.03, compared with ischemia detected only at the ECG exercise test) were at higher risk and those with both these components showing even >10-fold event rates as compared with the absence of both. Three-hundred and twenty-five patients (34%) continued to experience angina, 69 (7.2%) underwent repeat coronary angiography, and 14 (1.5%) had consequent coronary revascularization for atherosclerosis progression. CONCLUSION: Apart from the impaired quality of life, angina without obstructive CAD has an overall benign but very heterogeneous prognosis. Nonobstructive CAD and myocardial ischemia at imaging tests both confer a higher risk.
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Angina de Pecho , Enfermedad de la Arteria Coronaria , Isquemia Miocárdica , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Humanos , Pronóstico , Calidad de Vida , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Impaired glucose tolerance (IGT) has been related to adverse cardiovascular outcomes. We investigated the added value of 1-h plasma glucose (PG) at the oral glucose tolerance test (OGTT) in predicting admission and peak cardiac high-sensitivity troponin T (hs-TnT) and NT-proBNP values in IGT patients admitted for an acute coronary syndrome (ACS). RESEARCH DESIGN AND METHODS: Among 192 consecutive ACS patients, 109 had Hb1Ac and fasting plasma glucose negative for newly diagnosed diabetes. Upon OGTT performed > 96 h after admission, 88, conventionally diagnosed as IGT, were divided into: "full glucose tolerance" (1-h PG-OGTT < 155 mg/dL and 2-h PG-OGTT < 140 mg/dL, N = 12);"early IGT" (1 h-PG-OGTT ≥ 155 mg/dL and 2-h PG-OGTT < 140 mg/dL, N = 33);"late IGT" (1-h PG-OGTT < 155 mg/dL and 2-h PG-OGTT ≥ 140 mg/dL, N = 8); and "full IGT" (1-h PG-OGTT ≥ 155 mg/dL and 2-h PG-OGTT ≥ 140 mg/dL, N = 35). The 4 groups were compared for cardiac markers. RESULTS: The first three groups had similar cardiac marker values, but only full IGT patients had significantly higher admission hs-TnT compared with the 3 other groups [median (interquartile range): 911 (245-2976) vs 292 (46-1131), P < 0.001]. Full IGT patients also had higher hs-TnT peak compared with fully glucose tolerant and early IGT patients. Only full IGT patients had longer hospitalization and higher NT-proBNP vs fully glucose tolerant patients (P = 0.005). CONCLUSIONS: Among non-diabetic ACS patients, only those with both 1-h PG ≥ 155 mg/dL and 2-h PG ≥ 140 mg/dL had more severe myocardial injury and longer hospitalization. One-h PG-OGTT importantly contributes to assessing post-ACS cardiac risk.
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Síndrome Coronario Agudo , Intolerancia a la Glucosa , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/etiología , Biomarcadores , Glucemia , Glucosa , Prueba de Tolerancia a la Glucosa , HumanosRESUMEN
AIMS: Frailty is common in patients with atrial fibrillation (AF), with possible impact on therapies and outcomes. However, definitions of frailty are variable, and may not overlap with frailty perception among physicians. We evaluated the prevalence of frailty as perceived by enrolling physicians in the Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular AF (ETNA-AF)-Europe registry (NCT02944019), and compared it with an objective frailty assessment. METHODS AND RESULTS: ETNA-AF-Europe is a prospective, multi-centre, post-authorization, observational study. There we assessed the presence of frailty according to (i) a binary subjective investigators' judgement and (ii) an objective measure, the Modified Frailty Index. Baseline data on frailty were available in 13 621/13 980 patients. Prevalence of perceived frailty was 10.6%, with high variability among participating countries and healthcare settings (range 5.9-19.6%). Conversely, only 5.0% of patients had objective frailty, with minimal variability (range 4.5-6.7%); and only <1% of patients were identified as frail by both approaches. Compared with non-frailty-perceived, perceived frail patients were older, more frequently female, and with lower body weight; conversely, objectively frail patients had more comorbidities. Non-recommended edoxaban dose regimens were more frequently prescribed in both frail patient categories. CONCLUSIONS: Physicians' perception of frailty in AF patients is variable, mainly driven by age, sex, and weight, and quite different compared with the results of an objective frailty assessment. Whatever the approach, frailty appears to be associated with non-recommended anticoagulant dosages. Whether this apparent inappropriateness influences hard outcomes remains to be assessed.
Asunto(s)
Fibrilación Atrial , Fragilidad , Accidente Cerebrovascular , Administración Oral , Anticoagulantes , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Europa (Continente)/epidemiología , Femenino , Fragilidad/diagnóstico , Fragilidad/epidemiología , Humanos , Estudios Prospectivos , Piridinas , Accidente Cerebrovascular/epidemiología , TiazolesRESUMEN
Air pollutants are a complex mixture of gaseous substances and particulate matter (PM). Each component potentially has specific harmful effects on human health, but several experimental and clinical studies have shown a strong impact of fine particles on major adverse cardiovascular events. Most of the available evidence concerns the effects of exposure to PM with a diameter of <2.5â µm (PM2.5) and the risk of developing coronary heart disease through inflammation and oxidative stress. While prolonged exposure to PM2.5 has been shown to be associated with the development of atherosclerosis and cardio-metabolic risk factors, short-term exposure has instead proved to be a trigger for acute coronary events, and especially in subjects with pre-existing coronary artery disease. As such, environmental PM2.5 is a major risk element for global public health. This underlines on the one hand not only the need to adopt and encourage preventive measures especially for individuals with a higher risk profile but also to practice environmental policies that are effective in promoting the reduction of exposure to pollutants.