The importance of the left atrium in cardiovascular performance has long been acknowledged. Quantitative assessment of left atrial (LA) function is laborious, requiring invasive pressure-volume loops ...and thus precluding its routine clinical use. In recent years, novel postprocessing imaging methodologies have emerged, providing a complementary approach for the assessment of the left atrium. Atrial strain and strain rate obtained using either Doppler tissue imaging or two-dimensional speckle-tracking echocardiography have proved to be feasible and reproducible techniques to evaluate LA mechanics. It is essential to fully understand the clinical applications, advantages, and limitations of LA strain and strain rate analysis. Furthermore, the technique's prognostic value and utility in therapeutic decisions also need further elucidation. The aim of this review is to provide a critical appraisal of LA mechanics. The authors describe the fundamental concepts and methodology of LA strain and strain rate analysis, the reference values reported with different imaging techniques, and the clinical implications.
Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse limb events (MALE). The efficacy and safety of direct oral anticoagulants (DOACs) in this context ...is evolving. To assess the efficacy and safety of DOAC combined with aspirin compared to the use of antiplatelet agents in patients with symptomatic lower extremity (LE) PAD. We systematically searched PubMed, Embase and Cochrane databases, in September 2020, for randomized controlled trials (RCTs) that were designed to investigate the effect of DOACs in the treatment of PAD. A random-effects meta-analysis was performed targeting ischemic and bleeding events. Three randomized clinical trials were included, providing a total of 9533 patients, and 744 pooled MALE events (316 in DOAC plus aspirin and 428 in control). Only data on rivaroxaban and edoxaban were available. The use of DOAC plus aspirin in PAD patients significantly decreased the rate of MALE (pooled OR 0.70 0.61–0.83, P < 0.001; I
2
= 0%). In terms of safety, there was a significantly higher rate of major bleeding events (pooled OR 1.46 1.16–1.84, P = 0.001; I
2
= 52%). In rivaroxaban-RCTs, the addition of low-dose rivaroxaban to aspirin was still associated with a lower MALE compared to aspirin alone (pooled OR 0.68 0.53–0.88, P = 0.003; I
2
= 28%), but also conferred higher major bleeding rate (pooled OR 1.48 1.18–1.86, P < 0.001; I
2
= 0%). In conclusion, our pooled data suggests that for patients with symptomatic LE-PAD, the use of DOAC combined with aspirin reduced the risk of major ischemic limb events at the expense of an increased risk of major bleeding.
To describe the annual incidence and the leading causes of sudden non-cardiac and cardiac death (SCD) in children and young adult Portuguese population. We retrospectively reviewed autopsy of sudden ...unexpected deaths reports from the Portuguese National Institute of Legal Medicine and Forensic Sciences' database, between 2012 and 2016, for the central region of Portugal, Azores and Madeira (ages 1-40: 26% of the total population). During a 5-year period, 159 SD were identified, corresponding to an annual incidence of 2,4 (95%confidence interval, 1,5-3,6) per 100.000 people-years. Victims had a mean age of 32 ± 7 years-old, and 72,3% were male. There were 70,4% cardiac, 16,4% respiratory and 7,5% neurologic causes of SD. The most frequent cardiac anatomopathological diagnosis was atherosclerotic coronary artery disease (CAD) (33,0%). There were 15,2% victims with left ventricular hypertrophy, with a diagnosis of hypertrophic cardiomyopathy only possible in 2,7%. The prevalence of cardiac pathological findings of uncertain significance was 30,4%. In conclusion, the annual incidence of SD was low. Atherosclerotic CAD was diagnosed in 33,0% victims, suggesting the need to intensify primary prevention measures in the young. The high prevalence of pathological findings of uncertain significance emphasizes the importance of molecular autopsy and screening of first-degree relatives.
Pericarditis is a common condition with numerous aetiologies. Bacteria other than the
complex are an exceptional cause. We present a case of subacute pericarditis highly probable due to
subsp.
in an ...immunosuppressed patient undergoing biologic therapy in relation to systemic lupus erythematosus (SLE). On admission, the patient presented with chest pain, dyspnea, and diaphoresis and has lately developed fever and a large pericardial effusion (PE) with a concomitant increase in the inflammatory parameters. The clinical presentation, along with the exclusion of a flare of the autoimmune disease and the isolation of
subsp.
on blood samples permitted the diagnosis. After therapy with antibiotics and colchicine, the patient showed full recovery.
RATIONALE:Efficient communication between heart cells is vital to ensure the anisotropic propagation of electrical impulses, a function mainly accomplished by gap junctions (GJ) composed of Cx43 ...(connexin 43). Although the molecular mechanisms remain unclear, altered distribution and function of gap junctions have been associated with acute myocardial infarction and heart failure.
OBJECTIVE:A recent proteomic study from our laboratory identified EHD1 (Eps15 endocytic adaptor epidermal growth factor receptor substrate 15 homology domain-containing protein 1) as a novel interactor of Cx43 in the heart.
METHODS AND RESULTS:In the present work, we demonstrate that knockdown of EHD1 impaired the internalization of Cx43, preserving gap junction-intercellular coupling in cardiomyocytes. Interaction of Cx43 with EHD1 was mediated by Eps15 and promoted by phosphorylation and ubiquitination of Cx43. Overexpression of wild-type EHD1 accelerated internalization of Cx43 and exacerbated ischemia-induced lateralization of Cx43 in isolated adult cardiomyocytes. In addition, we show that EHDs associate with Cx43 in human and murine failing hearts.
CONCLUSIONS:Overall, we identified EHDs as novel regulators of endocytic trafficking of Cx43, participating in the pathological remodeling of gap junctions, paving the way to innovative therapeutic strategies aiming at preserving intercellular communication in the heart.
In recent years, the role of arterial stiffness in the development of cardiovascular diseases has been explored more extensively. Local arterial stiffness may be gauged via ultrasound, measuring ...pulse transit time relative to changing vessel diameters and distending pressures. Recently, direct vessel-wall tracking systems have been devised based on new ultrasonographic methodologies, such as tissue Doppler imaging and speckle-tracking analysis--vascular mechanics. These advances have been evaluated in varying arterial distributions, are proved surrogates of pulse wave velocity, and are ascending in clinical importance. In the course of this review, we describe fundamental concepts and methodologies involved in ultrasound assessment of vascular mechanics. We also present relevant clinical studies and discuss the potential clinical utility of such diagnostic pursuits.
Endothelium, the gatekeeper of our blood vessels, is highly heterogeneous and a crucial physical barrier with the ability to produce vasoactive and protective mediators under physiological ...conditions. It regulates vascular tone, haemostasis, vascular inflammation, remodelling, and angiogenesis. Several cardio-, reno-, and cerebrovascular diseases begin with the dysfunction of endothelial cells, and more recently, COVID-19 was also associated with endothelial disease highlighting the need to monitor its function towards prevention and reduction of vascular dysfunction. Endothelial cells are an important therapeutic target in predictive, preventive, and personalised (3P) medicine with upmost importance in vascular diseases. The development of novel non-invasive techniques to access endothelial dysfunction for use in combination with existing clinical imaging modalities provides a feasible opportunity to reduce the burden of vascular disease.
This review summarises recent advances in the principles of endothelial function measurements. This article presents an overview of invasive and non-invasive techniques to determine vascular function and their major advantages and disadvantages. In addition, the article describes mechanisms underlying the regulation of vascular function and dysfunction and potential new biomarkers of endothelial damage. Recognising these biomarkers is fundamental towards a shift from reactive to 3P medicine in the vascular field. Identifying vascular dysfunction earlier with non-invasive or minimally invasive techniques adds value to predictive diagnostics and targeted prevention (primary, secondary, tertiary care). In addition, vascular dysfunction is a potential target for treatments tailored to the person.
Fluorine-18 sodium fluoride (Na18FF) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global ...cardiac microcalcification activity with Na18FF, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients.
Thirty-four high CV risk individuals without previous CV events were scanned with Na18FF PET-CT. Cardiac Na18FF uptake was assessed through the global molecular calcium score (GMCS), which was calculated by summing the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. Mean age is 63.5 ± 7.8 years and 62% male. Median GMCS is 320.9 (240.8-402.8). Individuals with more than five CV risk factors (50%) have increased GMCS 356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), P = 0.01, which is positively correlated with predicted fatal CV risk by SCORE (rs = 0.32, P = 0.04). There is a positive correlation between GMCS and weight (rs = 0.61), body mass index (rs = 0.66), abdominal perimeter (rs = 0.74), thoracic fat volume (rs = 0.47), and epicardial adipose tissue (rs = 0.41), all with P ≤ 0.01. There is no correlation between GMCS and coronary calcium score nor coronary artery wall Na18FF uptake.
In a high CV risk group, the global cardiac microcalcification burden is related to CV risk factors, metabolic syndrome variables and cardiac fat. Cardiac GMCS is a promising risk stratification tool, combining a straightforward and objective methodology with a comprehensive analysis of both coronary and valvular microcalcification.
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