Atrial High-Rate Episode Duration Thresholds and Thromboembolic Risk: A Systematic Review and Meta-Analysis

BACKGROUND: Available evidence supports an association between atrial high‐rate episode (AHRE) burden and thromboembolic risk, but the necessary extent and duration of AHREs to increase the thromboembolic risk remain to be defined. The aim of this systematic review and meta‐analysis was to identify the thromboembolic risk associated with various AHRE thresholds. METHODS AND RESULTS: We searched PubMed and Scopus until January 9, 2020, for literature reporting AHRE duration and thromboembolic risk in patients with implantable electronic devices. The outcome assessed was stroke or systemic embolism. Risk estimates were reported as hazard ratio (HR) or relative risk alongside 95% CIs. We used the Paule‐Mandel estimator, and heterogeneity was calculated with I(2) index. Among 27 studies including 61 919 patients, 23 studies reported rates according to the duration of the longest AHRE and 4 studies reported rates according to the cumulative day‐level AHRE duration. In patients with cardiac implantable devices, AHREs lasting ≥30 seconds significantly increased the risk of stroke or systemic embolism (HR, 4.41; 95% CI, 2.32–8.39; I(2), 5.5%), which remained consistent for the thresholds of 5 minutes and 6 and 24 hours. Patients with previous stroke or transient ischemic attack and AHREs lasting ≥2 minutes had a marginally increased risk of recurrent stroke or transient ischemic attack. The risk of stroke or systemic embolism was higher in patients with cumulative AHRE ≥24 hours compared with those of shorter duration or no AHRE (HR, 1.25; 95% CI, 1.04–1.52; I(2), 0%). CONCLUSIONS: This systematic review and meta‐analysis suggests that single AHRE episodes ≥30 seconds and cumulative AHRE duration ≥24 hours are associated with increased risk of stroke or systemic embolism

Comparative efficacy and safety of mineralocorticoid receptor antagonists in patients with heart failure and reduced ejection fraction: a systematic review and network meta-analysis

The primary objectives of the present study will be to assess the comparative efficacy and safety of different mineralocortiocoid receptor antagonists (MRAs) on hard and surrogate outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and a left ventricular ejection fraction (LVEF) of no more than 45%

Antithrombotic Treatment in Cryptogenic Stroke Patients With Patent Foramen Ovale:Systematic Review and Meta-Analysis

Background and Purpose- It is unclear whether treatment with anticoagulants or antiplatelets is the optimal strategy in patients with stroke or transient ischemic attack of undetermined cause and patent foramen ovale that is not percutaneously closed. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare anticoagulant or antiplatelet treatment in this population. Methods- We searched PubMed until July 16, 2019 for trials comparing anticoagulants and antiplatelet treatment in patients with stroke/transient ischemic attack and medically treated patent foramen ovale using the terms: "cryptogenic or embolic stroke of undetermined source" and "stroke or cerebrovascular accident or transient ischemic attack" and "patent foramen ovale or patent foramen ovale or paradoxical embolism" and "trial or study" and "antithrombotic or anticoagulant or antiplatelet." The outcomes assessed were stroke recurrence, major bleeding, and the composite end point of stroke recurrence or major bleeding. We used 3 random-effects models: (1) a reference model based on the inverse variance method with the Sidik and Jonkman heterogeneity estimator; (2) a strict model, implementing the Hartung and Knapp method; and (3) a commonly used Bayesian model with a prior that assumes moderate to large between-study variance. Results- Among 112 articles identified in the literature search, 5 randomized controlled trials were included in the meta-analysis (1720 patients, mean follow-up 2.3±0.5 years). Stroke recurrence occurred at a rate of 1.73 per 100 patient-years in anticoagulant-assigned patients and 2.39 in antiplatelet-assigned patients (hazard ratio, 0.68; 95% CI, 0.32-1.48 for the Sidik and Jonkman estimator). Major bleeding occurred at a rate of 1.16 per 100 patient-years in anticoagulant-assigned patients and 0.68 in antiplatelet-assigned patients (hazard ratio, 1.61; 95% CI, 0.72-3.59 for the Sidik and Jonkman estimator). The composite outcome occurred in 52 anticoagulant-assigned and 54 antiplatelet-assigned patients (odds ratio, 1.05; 95% CI, 0.65-1.70 for the Sidik and Jonkman estimator). Conclusions- We cannot exclude a large reduction of stroke recurrence in anticoagulant-assigned patients compared with antiplatelet-assigned, without significant differences in major bleeding. An adequately powered randomized controlled trial of a non-vitamin K antagonist versus aspirin is warranted

Antithrombotic Treatment in Cryptogenic Stroke Patients With Patent Foramen Ovale : Systematic Review and Meta-Analysis

Background and Purpose- It is unclear whether treatment with anticoagulants or antiplatelets is the optimal strategy in patients with stroke or transient ischemic attack of undetermined cause and patent foramen ovale that is not percutaneously closed. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare anticoagulant or antiplatelet treatment in this population. Methods- We searched PubMed until July 16, 2019 for trials comparing anticoagulants and antiplatelet treatment in patients with stroke/transient ischemic attack and medically treated patent foramen ovale using the terms: "cryptogenic or embolic stroke of undetermined source" and "stroke or cerebrovascular accident or transient ischemic attack" and "patent foramen ovale or patent foramen ovale or paradoxical embolism" and "trial or study" and "antithrombotic or anticoagulant or antiplatelet." The outcomes assessed were stroke recurrence, major bleeding, and the composite end point of stroke recurrence or major bleeding. We used 3 random-effects models: (1) a reference model based on the inverse variance method with the Sidik and Jonkman heterogeneity estimator; (2) a strict model, implementing the Hartung and Knapp method; and (3) a commonly used Bayesian model with a prior that assumes moderate to large between-study variance. Results- Among 112 articles identified in the literature search, 5 randomized controlled trials were included in the meta-analysis (1720 patients, mean follow-up 2.3±0.5 years). Stroke recurrence occurred at a rate of 1.73 per 100 patient-years in anticoagulant-assigned patients and 2.39 in antiplatelet-assigned patients (hazard ratio, 0.68; 95% CI, 0.32-1.48 for the Sidik and Jonkman estimator). Major bleeding occurred at a rate of 1.16 per 100 patient-years in anticoagulant-assigned patients and 0.68 in antiplatelet-assigned patients (hazard ratio, 1.61; 95% CI, 0.72-3.59 for the Sidik and Jonkman estimator). The composite outcome occurred in 52 anticoagulant-assigned and 54 antiplatelet-assigned patients (odds ratio, 1.05; 95% CI, 0.65-1.70 for the Sidik and Jonkman estimator). Conclusions- We cannot exclude a large reduction of stroke recurrence in anticoagulant-assigned patients compared with antiplatelet-assigned, without significant differences in major bleeding. An adequately powered randomized controlled trial of a non-vitamin K antagonist versus aspirin is warranted

Adherence to an integrated care pathway for stroke is associated with lower risk of major cardiovascular events: A report from the Athens Stroke Registry

BACKGROUND: A recent European Society of Cardiology (ESC) Council on Stroke position paper proposed a holistic integrated care management approach for stroke patients, to improve cardiovascular outcomes. The impact of implementing the ABCstroke pathway 'concept' on clinical outcomes has never been estimated before. In order to investigate the potential effect of ABCstroke pathway adherence to cardiovascular outcomes post stroke, we performed a post-hoc analysis from the Athens Stroke Registry.METHODS AND RESULTS: This analysis was performed in the Athens Stroke Registry, which includes all consecutive patients with acute first-ever ischemic stroke. The Kaplan-Meier product limit was used to estimate the cumulative hazard of each outcome according to adherence with the ABCstroke pathway. We studied 2513 patients [median (IQR) age 71 (62-78) years; 37.7 % female] with ischemic stroke with median follow-up period of 30 (6-75) months. Full adherence to the ABC pathway was identified in 156 (6.2 %) of the patients, while 192 (7.6 %) did not adhere to any of the therapeutic pillars of ABCstroke. Full adherence to ABC treatment pathway was associated with significant reduction of stroke recurrence, compared to patients with no or partial adherence (aHR: 0.61; 95 %CI: 0.37-0.99), as well as a lower risk of MACE (HR: 0.59; 0.39-0.88) and death (aHR: 0.22; 95 %CI: 0.12-0.41).CONCLUSION: Full adherence to the ABCstroke pathway based on the current guidelines was evident in only 6.2 % of our ischaemic stroke cohort but was independently associated with lower risks of stroke recurrence, major cardiovascular events and mortality. This highlights a potential opportunity to improve clinical outcomes post-stroke with a holistic or integrated care management approach.</p

Telomere Length: A Cardiovascular Biomarker and a Novel Therapeutic Target

Coronary artery disease (CAD) is a multifactorial disease with a high prevalence, particularly in developing countries. Currently, the investigation of telomeres as a potential tool for the early detection of the atherosclerotic disease seems to be a promising method. Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere length (TL) has been associated with several human disorders and diseases while its attrition rate varies significantly in the population. The rate of TL shortening ranges between 20 and 50 bp and is affected by factors such as the end-replication phenomenon, oxidative stress, and other DNA-damaging agents. In this review, we delve not only into the pathophysiology of TL shortening but also into its association with cardiovascular disease and the progression of atherosclerosis. We also provide current and future treatment options based on TL and telomerase function, trying to highlight the importance of these cutting-edge developments and their clinical relevance

Non-Invasive Modalities in the Assessment of Vulnerable Coronary Atherosclerotic Plaques

Coronary atherosclerosis is a complex, multistep process that may lead to critical complications upon progression, revolving around plaque disruption through either rupture or erosion. Several high-risk features are associated with plaque vulnerability and may add incremental prognostic information. Although invasive imaging modalities such as optical coherence tomography or intravascular ultrasound are considered to be the gold standard in the assessment of vulnerable coronary atherosclerotic plaques (VCAPs), contemporary evidence suggests a potential role for non-invasive methods in this context. Biomarkers associated with deleterious pathophysiologic pathways, including inflammation and extracellular matrix degradation, have been correlated with VCAP characteristics and adverse prognosis. However, coronary computed tomography (CT) angiography has been the most extensively investigated technique, significantly correlating with invasive method-derived VCAP features. The estimation of perivascular fat attenuation as well as radiomic-based approaches represent additional concepts that may add incremental information. Cardiac magnetic resonance imaging (MRI) has also been evaluated in clinical studies, with promising results through the various image sequences that have been tested. As far as nuclear cardiology is concerned, the implementation of positron emission tomography in the VCAP assessment currently faces several limitations with the myocardial uptake of the radiotracer in cases of fluorodeoxyglucose use, as well as with motion correction. Moreover, the search for the ideal radiotracer and the most adequate combination (CT or MRI) is still ongoing. With a look to the future, the possible combination of imaging and circulating inflammatory and extracellular matrix degradation biomarkers in diagnostic and prognostic algorithms may represent the essential next step for the assessment of high-risk individuals