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Background: A high-cholesterol diet (HCD) induces vascular atherosclerosis through vascular inflammatory and immunological processes via TLRs. The aim of this study is to investigate the mRNA expression of TLRs and other noxious biomarkers expressing inflammation, fibrosis, apoptosis, and cardiac dysfunction in the rabbit myocardium during (a) high-cholesterol diet (HCD), (b) normal diet resumption and (c) fluvastatin or rosuvastatin treatment. Methods: Forty-eight male rabbits were randomly divided into eight groups (n = 6/group). In the first experiment, three groups were fed with HCD for 1, 2 and 3 months. In the second experiment, three groups were fed with HCD for 3 months, followed by normal chow for 1 month and administration of fluvastatin or rosuvastatin for 1 month. Control groups were fed with normal chow for 90 and 120 days. The whole myocardium was removed, total RNA was isolated from acquired samples, and polymerase chain reaction, reverse transcription PCR and quantitative real-time PCR were performed. Results: mRNA of TLRs 2, 3, 4 and 8, interleukin-6, TNF-a, metalloproteinase-2, tissue inhibitor of metalloproteinase-1, tumor protein 53, cysteinyl aspartate specific proteinase-3, and brain natriuretic peptide (BNP) increased in HCD. Statins but not resumption of a normal diet decreased levels of these biomarkers and increased levels of antifibrotic factors. Conclusions: HCD increases the levels of TLRs, inflammatory, fibrotic and apoptotic factors, and BNP in the rabbit myocardium. Atherogenic diets adversely affect the myocardium at a molecular level and are reversed by statins.

Preclinical data suggest that the ageing-induced miR-34a regulates vascular senescence. Herein we sought to assess whether the miR-34 family members miR-34a, miR-34b and miR-34c are involved in human arterial disease.Expression levels of miR-34a/b/c were quantified by TaqMan assay in peripheral blood mononuclear cells (PBMCs) derived from a consecutive cohort of 221 subjects who underwent cardiovascular risk assessment and thorough vascular examination for aortic stiffness and extent of arterial atherosclerosis.High miR-34a was independently associated with the presence of CAD [OR (95%C.I.): 3.87 (1.56-9.56); p = 0.003] and high miR-34c with the number of diseased arterial beds [OR (95%C.I.): 1.88 (1.034-3.41); p = 0.038], while concurrent high expression of miR-34-a/c or all three miR-34a/b/c was associated with aortic stiffening (miR-34a/c: p = 0.022; miR-34a/b/c: p = 0.041) and with the extent of atherosclerosis [OR (95%C.I.) for number of coronary arteries [miR-34a/c: 3.29 (1.085-9.95); miR-34a/b/c: 6.06 (1.74-21.2)] and number of diseased arterial beds [miR-34a/c: 3.51 (1.45-8.52); miR-34a/b/c: 2.89 (1.05-7.92)] after controlling for possible confounders (p 0.05 for all). Mechanistically, the increased levels of miR-34a or miR-34c were inversely associated with expression of SIRT1 or JAG1, NOTCH2, CTNNB1 and ATF1, respectively. The association of miR-34a/c or miR-34a/b/c with CAD was mainly mediated through SIRT1 and to a lesser extent through JAG1 as revealed by generalized structural equation modeling. Leukocyte-specific ablation of miR-34a/b/c ameliorates atherosclerotic plaque development and increases Sirt1 and Jag1 expression in an atherosclerosis mouse model confirming the human findings.The present study reveals the clinical significance of the additive role of miR-34a/b/c in vascular ageing and atherosclerotic vascular disease.

Coronary artery disease (CAD) is known to impact on patients’ physical and mental health. The relationship between performance on treadmill exercise tolerance test (ETT) and health-related quality of life (HRQL)has never been specifically investigated in the setting of CAD. Consecutive patients undergoing an ETT with the Bruce protocol during a diagnostic workup for CAD (n = 1,631, age 55 ± 12 years) were evaluated. Exercise-related indices were recorded. Detailed information on cardiovascular risk factors and past medical history were obtained. HRQLwas assessed with the use of the validated 36-Item Short Form Survey (SF-36) questionnaire. Increasing age and the presence of cardiovascular risk factors and comorbidities correlated with lower scores on the physical and mental health component of SF-36(all P

Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events (CVAEs). We prospectively investigated the effect of CFZ on endothelial function and associations with CVAEs. Forty-eight patients treated with Kd (CFZ 20/56 mg/m2 and dexamethasone) underwent serial endothelial function evaluation, using brachial artery flow-mediated dilatation (FMD) and 26S proteasome activity (PrA) measurement in PBMCs; patients were followed until disease progression or cycle 6 for a median of 10 months. FMD and PrA decreased acutely after the first dose (p 40% at the end of first cycle was also independently associated with CVAEs (HR = 3.91, 95% CI 1.29–11.83). Kd treatment impairs endothelial function which is associated with PrA inhibition and recovery. Both pre- and posttreatment FMD predicted CFZ-related CVAEs supporting its role as a possible cardiovascular toxicity biomarker.

Objectives This study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years. Background Greater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood. Methods Associations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences. Results Fat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p Conclusions Subtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures might be more appropriate for the identification of arterial disease before adulthood.

BACKGROUND Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium. They also have low levels of endothelial progenitor cells (EPCs). EPCs are bone marrow derived cells involved in endothelium regeneration, homeostasis, and neovascularization. Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities. However, the effects of exercise on EPCs in different stages of CHF remain under investigation. AIM To evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing (CPET) on EPCs in CHF patients of different severity. METHODS Forty-nine consecutive patients (41 males) with stable CHF [mean age (years): 56 ± 10, ejection fraction (EF, %): 32 ± 8, peak oxygen uptake (VO2, mL/kg/min): 18.1 ± 4.4] underwent a CPET on a cycle ergometer. Venous blood was sampled before and after CPET. Five circulating endothelial populations were quantified by flow cytometry: Three subgroups of EPCs [CD34+/CD45-/CD133+, CD34+/CD45-/CD133+/VEGFR2 and CD34+/CD133+/vascular endothelial growth factor receptor 2 (VEGFR2)] and two subgroups of circulating endothelial cells (CD34+/CD45-/CD133- and CD34+/CD45-/CD133-/VEGFR2). Patients were divided in two groups of severity according to the median value of peak VO2 (18.0 mL/kg/min), predicted peak VO2 (65.5%), ventilation/carbon dioxide output slope (32.5) and EF (reduced and mid-ranged EF). EPCs values are expressed as median (25th-75th percentiles) in cells/106 enucleated cells. RESULTS Patients with lower peak VO2 increased the mobilization of CD34+/CD45-/CD133+ [pre CPET: 60 (25-76) vs post CPET: 90 (70-103) cells/106 enucleated cells, P < 0.001], CD34+/CD45-/CD133+/VEGFR2 [pre CPET: 1 (1-4) vs post CPET: 5 (3-8) cells/106 enucleated cells, P < 0.001], CD34+/CD45-/CD133- [pre CPET: 186 (141-361) vs post CPET: 488 (247-658) cells/106 enucleated cells, P < 0.001] and CD34+/CD45-/CD133-/VEGFR2 [pre CPET: 2 (1-2) vs post CPET: 3 (2-5) cells/106 enucleated cells, P < 0.001], while patients with higher VO2 increased the mobilization of CD34+/CD45-/CD133+ [pre CPET: 42 (19-73) vs post CPET: 90 (39-118) cells/106 enucleated cells, P < 0.001], CD34+/CD45-/CD133+/VEGFR2 [pre CPET: 2 (1-3) vs post CPET: 6 (3-9) cells/106 enucleated cells, P < 0.001], CD34+/CD133+/VEGFR2 [pre CPET: 10 (7-18) vs post CPET: 14 (10-19) cells/106 enucleated cells, P < 0.01], CD34+/CD45-/CD133- [pre CPET: 218 (158-247) vs post CPET: 311 (254-569) cells/106 enucleated cells, P < 0.001] and CD34+/CD45-/CD133-/VEGFR2 [pre CPET: 1 (1-2) vs post CPET: 4 (2-6) cells/106 enucleated cells, P < 0.001]. A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak, ventilation/carbon dioxide output slope and EF as well (P < 0.05). However, there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison (P > 0.05). CONCLUSION Our study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients, but this increase was not associated with syndrome severity. Further investigation, however, is needed.

Background Preventing the evolution of subclinical cardiac disease into overt heart failure is of paramount importance. Imaging techniques, particularly transthoracic echocardiography (TTE), are well suited to identify abnormalities in cardiac structure and function that precede the development of heart failure. Methods This meta-analysis provides a comprehensive evaluation of 32 studies from 11 individual cohorts, which assessed cardiac indices from TTE (63%), cardiovascular magnetic resonance (CMR; 34%) or cardiac computed tomography (CCT; 16%). Eligible studies focused on measures of left ventricular geometry and function and were highly heterogeneous. Results Among the variables that could be assessed through a meta-analytic approach, left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) lower than 50%, and left ventricular dilation were associated with a five-fold [hazard ratio (HR) 4.76, 95% confidence interval (95% CI) 1.85-12.26] and three-fold (HR 3.14, 95% CI 1.37 -7.19) increased risk of heart failure development, respectively. Any degree of diastolic dysfunction conveyed an independent, albeit weaker, association with heart failure (HR 1.48, 95% CI 1.11-1.96), although there was only a trend for left ventricular hypertrophy in predicting incident heart failure (hazard ratio 2.85, 95% CI 0.82-9.85). Conclusion LVEF less than 50%, left ventricular dilation and diastolic dysfunction are independent predictors of incident heart failure among asymptomatic individuals, while left ventricular hypertrophy seems less predictive. These findings may serve as a framework for implementing imaging-based screening strategies in patients at risk of heart failure and inform future studies testing preventive or therapeutic approaches aiming at thwarting or halting the progression from asymptomatic (preclinical) to overt heart failure.

The significant morbidity and mortality associated with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. Reduced cyclic guanosine monophosphate levels contribute to HF progression. Among molecules modulating the nitric oxide (NO)–GMP–phosphodiesterase (PDE) pathway, the evaluation of nitrates, synthetic natriuretic peptides (NP), and NP analogs has yielded mixed results. Conversely, sacubitril/valsartan, combining NP degradation inhibition through neprilysin and angiotensin receptor blockade, has led to groundbreaking findings in HFrEF. Other strategies to increase tissue cyclic guanosine monophosphate have been attempted, such as PDE-3 or PDE-5 inhibition (with negative or neutral results), NO-independent soluble guanylate cyclase (sGC) activation, or enhancement of sGC sensitivity to endogenous NO. Following the positive results of the phase 3 VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial on the sGC stimulator vericiguat in HFrEF, the main open questions are the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF and of vericiguat in HFpEF.

Objectives T2*-weighted (T2*w) is deemed as a reference standard for post-infarction intramyocardial haemorrhage (IMH). However, high proportion of T2* images is affected by off-resonance artefacts hampering image interpretation. Diagnostic accuracy and precision of alternative techniques for IMH diagnosis and quantification have been seldomly investigated. Methods and results Between April 2016 and May 2017, 50 ST-segment elevation myocardial infarction patients (66% male, 57 ± 17 years) and 15 healthy controls (60% male, 58 ± 13) were consecutively enrolled. Subjects underwent head-to-head comparison of single mid-infarct slice acquired on black-blood T2-weighted short-TI-inversion recovery (T2w-STIR), bright-blood T2prep-steady-state-free precession (T2prep-SSFP), and T2/T1 maps for IMH diagnosis and quantification against T2*w. All images were graded for quality (grade 1: very poor; grade 4: excellent) and diagnostic confidence (Likert scale, 1: very unsure and 5: highly confident). Reduced relaxation time/hypointense region (hypocore) embedded in infarct-related oedema on T2 map, T1 map, and T2w-STIR had the best overall diagnostic accuracy (per-subject: 91%, 86%, and 86%, respectively; per segment: 95%, 93%, and 93%, respectively). By mixed-effects analysis, image quality, and diagnostic confidence were higher for T2 map and T1 maps than T2*w (p r > 0.7, p Conclusion Hypocore on T2/T1 map is the best alternative technique to T2*w for diagnosing and quantifying IMH in post-STEMI patients. Key Point • Mapping techniques are the best alternatives for diagnosing post-infarction intramyocardial haemorrhage. • Mapping techniques are valuable tools for imaging intramyocardial haemorrhage.

Accurate and reproducible diagnostic techniques are essential to detect left-sided cardiac thrombi [either in the left ventricle (LV) or in the left atrial appendage (LAA)] and to guide the onset and duration of antithrombotic treatment while minimizing the risk for thromboembolic and hemorrhagic events. We conducted a systematic review and meta-analysis aiming to compare the diagnostic performance of transthoracic echocardiography (TTE) vs. cardiac magnetic resonance (CMR) for the detection of LV thrombi, and transesophageal echocardiography (TEE) vs. computed tomography (CT) for the detection of LAA thrombi. Six studies were included in the first meta-analysis (TTE vs. CMR for LV thrombosis). Pooled sensitivity and specificity values were 62% [95% confidence interval (CI), 37–81%] and 97% (95% CI, 94–99%). The shape of the hierarchical summary receiver operating characteristic (HSROC) curve and the area under the curve (AUC) of 0.96 suggested a high accuracy. Ten studies were included in the second meta-analysis (CT versus TEE for LAA thrombosis). The pooled values of sensitivity and specificity were 97% (95% CI, 77–100%) and 94% (95% CI, 87–98%). The pooled diagnostic odds ratio (DOR) was 500 (95% CI, 52–4810), and the pooled likelihood ratios (LR + and LR−) were 17% (95% CI, 7–40%) and 3% (95% CI, 0–28%). The shape of the HSROC curve and 0.99 AUC suggested a high accuracy of CT vs. TEE. TTE is a fair alternative to DE-CMR for the identification of LV thrombi, while CT has a good accuracy compared to TEE for the detection of LAA thrombosis. CRD42020185842.

Objective Women with gestational diabetes mellitus (GDM) are at increased risk for adverse cardiovascular outcome later in life. However, it is uncertain whether this increased risk is due to cardiovascular changes occurring during pregnancy and persisting thereafter or to an adverse underlying cardiovascular risk factor profile. Some studies have reported that GDM is associated with reduced systolic and diastolic left ventricular function in pregnancy; however, it remains unknown whether these changes persist after delivery. The objective of this study was to compare cardiac function and structure in women with GDM and those with uncomplicated pregnancy at 35-36 weeks' gestation and about 6 months after delivery. Methods This was a longitudinal study in which women with GDM and those with uncomplicated pregnancy had detailed cardiovascular assessment at 35-36 weeks' gestation and repeat examination around 6 months after delivery. In all women, left ventricular systolic and diastolic indices were measured and left ventricular mass indexed for body surface area was calculated. Cardiac output and peripheral vascular resistance were also calculated using echocardiography. Linear mixed model analysis accounting for differences in maternal characteristics was carried out to compare findings of cardiovascular function between the GDM group and controls and within each group at 35-36 weeks' gestation and at 6 months after delivery. Results We studied 73 women with GDM and 73 controls with uncomplicated pregnancy. At 35-36 weeks' gestation, women with GDM, compared to controls, had higher E/e' ratio and lower E/A ratio and global longitudinal systolic strain; there were no significant differences between the groups in ejection fraction. Left ventricular mass indexed for body surface area was also increased in women with GDM. There were no significant differences between the groups in cardiac output and peripheral vascular resistance. At 6 months after delivery, cardiac functional indices improved in both patients with GDM and controls, but in the GDM group, compared to controls, there was a lower degree of improvement in E/A ratio and global longitudinal systolic strain. Conclusion In the third trimester, patients with GDM have subtle differences in diastolic and systolic left ventricular function compared to controls and, despite improvement after delivery, these changes persist for at least 6 months. Long-term follow-up is therefore needed to assess whether women with GDM are at risk for an accelerated decline in their cardiac function and, if so, whether this trend can be reversed or delayed by optimal cardiovascular risk factor modification. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Purpose Quantitative T1 , T2 , T2 *, and fat fraction (FF) maps are promising imaging biomarkers for the assessment of liver disease, however these are usually acquired in sequential scans. Here we propose an extended MR fingerprinting (MRF) framework enabling simultaneous liver T1 , T2 , T2 *, and FF mapping from a single ~14 s breath-hold scan. Methods A gradient echo (GRE) liver MRF sequence with nine readouts per TR, low flip angles (5-15°), varying magnetisation preparation and golden angle radial trajectory is acquired at 1.5T to encode T1 , T2 , T2 *, and FF simultaneously. The nine-echo time-series are reconstructed using a low-rank tensor constrained reconstruction and used to fit T2 *, B0 and to separate the water and fat signals. Water- and fat-specific T1 , T2, and M0 are obtained through dictionary matching, whereas FF estimation is extracted from the M0 maps. The framework was evaluated in a standardized T1 /T2 phantom, a water-fat phantom, and 12 subjects in comparison to reference methods. Preliminary clinical feasibility is shown in four patients. Results The proposed water T1 , water T2 , T2 *, and FF maps in phantoms showed high coefficients of determination (r2 > 0.97) relative to reference methods. Measured liver MRF values in vivo (mean ± SD) for T1 , T2 , T2 *, and FF were 671 ± 60 ms, 43.2 ± 6.8 ms, 29 ± 6.6 ms, and 3.2 ± 2.6% with biases of 92 ms, -7.1 ms, -1.4 ms, and 0.63% when compared to conventional methods. Conclusion A nine-echo liver MRF sequence allows for quantitative multi-parametric liver tissue characterization in a single breath-hold scan of ~14 s. Future work will aim to validate the proposed approach in patients with liver disease.

Prognostication after cardiac arrest (CA) represents a challenging issue, and several biomarkers have been proposed in the attempt to predict outcome. Among these, F2-isoprostanes stand out as potential biomarkers for early prognostication, providing information on the magnitude of global oxidative injury after return of spontaneous circulation (ROSC). We performed a topical review searching PubMed and Scopus databases to identify studies evaluating the modifications of F2-isoprostanes in the early period after CA, and a meta-analysis of studies providing curves of F2-isoprostanes plasma levels seeking to describe the biomarker's kinetics after CA. Evidence suggests that plasma levels of F2-isoprostanes increase in the early post-resuscitation period and seem well correlated with the burden of ischaemia-reperfusion injury. Our meta-analysis shows a possible increase as early as 5 minutes after ROSC, which persists at 2 hours and is attenuated at 4 hours. Clinical studies are warranted to evaluate the utility of this biomarker for prognostication purposes in CA survivors.

Background European data indicate that systemic sclerosis (SSc)-related death rates are increasing, thus raising concerns about SSc’s optimal management. Herein, we describe current treatment modalities and drug survival in a real-life SSc cohort. Methods Details on immunosuppressive/antiproliferative (methotrexate, mycophenolate, cyclophosphamide, azathioprine, rituximab, tocilizumab) and vasoactive agent [(endothelin receptor antagonists (ERAs), sildenafil, iloprost, and calcium channel blockers (CCB)] administration during the disease course (11.8 ± 8.4 years, mean + SD) of 497 consecutive patients examined between 2016 and 2018 were retrospectively recorded. Drug survival was assessed by Kaplan–Meier analysis. Results Methotrexate was the most frequently administered immunosuppressive/antiproliferative agent (53% of patients), followed by cyclophosphamide (26%), mycophenolate (12%), and azathioprine (11%). Regarding vasoactive agents, CCB had been ever administered in 68%, ERAs in 38%, iloprost in 7%, and sildenafil in 7% of patients; 23% of patients with pulmonary fibrosis had never received immunosuppressive/antiproliferative agents, 33% of those with digital ulcers had never received ERAs, iloprost, or sildenafil, whereas 19% of all patients had never received either immunosuppressive/antiproliferative or other than CCB vasoactive agents. Survival rates of methotrexate, cyclophosphamide, and mycophenolate differed significantly, being 84/75%, 59/43%, and 74/63% at 12/24 months, respectively, with inefficacy being the most frequent discontinuation cause. Conversely, CCB, ERAs, and sildenafil had high and comparable retention rates of 97/91%, 88/86%, and 80/80%, respectively. Conclusions Existing therapeutic limitations indicate that more evidence-based treatment is warranted for successful management of SSc. Vasculopathy seems to be managed more rigorously, but the low retention rates of immunosuppressive/antiproliferative drugs suggest that effective and targeted disease-modifying agents are warranted.

Background Diesel exhaust fumes represent one of the most common toxic pollutants. The prolonged effects of acute exposure to this pollutant on inflammatory status and vascular properties are unknown. Methods During a 2-h session, 40 healthy subjects were exposed to diesel exhaust fumes and/or filtered air. Endothelial function was assessed with flow mediated dilation, arterial stiffness with pulse wave velocity and reflected waves with augmentation index. C-reactive protein, fibrinogen, protein C levels and protein S activity were also measured. Standard deviation of normal to normal R–R intervals (SDNN) was used to assess heart rate variability. Measurements were assessed before exposure and 2 and 24 h after diesel exposure. Results Compared with filtered air, exposure to diesel exhaust fumes decreased flow mediated dilation and increased pulse wave velocity and augmentation index up to 24 h after the exposure (p Conclusion Short-term exposure to diesel exhaust fumes has a prolonged adverse impact on endothelial function and vascular wall properties, along with impaired heart rate variability, abnormal fibrinolytic activity and increased markers of inflammation. These findings give insights into the mechanisms underlining the increased cardiovascular risk of subjects regularly exposed to diesel exhaust fumes.

Objective: Inflammation, oxidative stress, and endothelial dysfunction are known to contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) protects from endothelial dysfunction and the damage induced by ischemia-reperfusion. Using intensive periodontal treatment (IPT), an established human model of acute systemic inflammation, we investigated whether RIPC prevents endothelial dysfunction and modulates systemic levels of inflammation and oxidative stress. Approach and Results: Forty-nine participants with periodontitis were randomly allocated to receive either 3 cycles of ischemia-reperfusion on the upper limb (N=24, RIPC) or a sham procedure (N=25, control) before IPT. Endothelial function assessed by flow-mediated dilatation of the brachial artery, inflammatory cytokines, markers of vascular injury, and oxidative stress were evaluated at baseline, day 1, and day 7 after IPT. Twenty-four hours post-IPT, the RIPC group had lower levels of IL-10 (interleukin-10) and IL-12 (interleukin-12) compared with the control group ( P P for interaction P for interaction P =0.011). After 7 days from IPT, most of the inflammatory markers, endothelial-dependent and -independent vasodilation, were similar between groups. Conclusions: RIPC prevented acute endothelial dysfunction by modulation of inflammation and oxidation processes in patients with periodontitis following exposure to an acute inflammatory stimulus. Registration: URL: https://clinicaltrials.gov/ct2/show/NCT03072342 ; Unique identifier: NCT03072342.

Objectives Decompressive hemicraniectomy decreases mortality and severe disability from space-occupying middle cerebral artery infarction in selected patients. However, attitudes towards hemicraniectomy for dominant-hemispheric stroke have been hesitant. This systematic review and meta-analysis examines the association of stroke laterality with outcome after hemicraniectomy. Materials and methods We performed a systematic literature search up to 6th February 2020 to retrieve original articles about hemicraniectomy for space-occupying middle cerebral artery infarction that reported outcome in relation to laterality. The primary outcome was severe disability (modified Rankin Scale 4‒6 or 5‒6 or Glasgow Outcome Scale 1‒3) or death. A two-stage combined individual patient and aggregate data meta-analysis evaluated the association between dominant-lateralized stroke and (a) short-term (≤ 3 months) and (b) long-term (> 3 months) outcome. We performed sensitivity analyses excluding studies with sheer mortality outcome, second-look strokectomy, low quality, or small sample size, and comparing populations from North America/Europe vs Asia/South America. Results The analysis included 51 studies (46 observational studies, one nonrandomized trial, and four randomized controlled trials) comprising 2361 patients. We found no association between dominant laterality and unfavorable short-term (OR 1.00, 95% CI 0.69‒1.45) or long-term (OR 1.01, 95% CI 0.76‒1.33) outcome. The results were unchanged in all sensitivity analyses. The grade of evidence was very low for short-term and low for long-term outcome. Conclusions This meta-analysis suggests that patients with dominant-hemispheric stroke have equal outcome after hemicraniectomy compared to patients with nondominant stroke. Despite the shortcomings of the available evidence, our results do not support withholding hemicraniectomy based on stroke laterality.

Background Smoking has been consistently associated with increased cardiovascular risk in adults. Although exposure to tobacco products often starts in early life, evidence for the possible adverse effects on the cardiovascular system of the young is scarce. We sought to derive pooled estimates of smoking effects on indices of early vascular damage in children and adolescents. Design and methods We performed a systematic review and meta-analysis of clinical studies involving young individuals up to 21 years old that provided data on smoking exposure (active or passive) and flow-mediated dilatation, carotid to femoral pulse wave velocity and maximum carotid intima-media thickness. We employed three distinct methodologies of random-effects data synthesis, including the Sidik-Jonkman estimator, the Hartung and Knapp correction and a Bayesian method with a well-informed prior on the level of between-study variance. Results In 12 studies and 5279 individuals in total, smoking exposure was related to deterioration in all three outcomes (mean adjusted flow-mediated dilatation decrease: −0.77%, 95% confidence interval −1.38–−0.15, mean adjusted pulse wave velocity increase: 0.1 m/s, 95% confidence interval 0.02–0.17 and mean adjusted carotid intima-media thickness increase: 0.35 mm, 95% confidence interval 0.16–0.55, for the Sidik-Jonkman estimator). No difference was established between active and passive smoking on associations with arterial damage. Conclusions Exposure to tobacco products is associated with subclinical vascular damage early in life, even from childhood. Public health initiatives should target these very young age groups to prevent early smoking exposure and associated arterial damage and its sequelae.

Major depression is associated with endothelial dysfunction and arterial stiffening, which may mediate development of hypertension and increased cardiovascular risk. The effect of response to antidepressant treatment on these vascular parameters has not been elucidated.We aimed to assess the net effect of antidepressant therapy on endothelial function and arterial stiffness in patients with psychotic depression.Thirty-seven patients with major psychotic depression, according to DSM-IV-TR, were treated with titrated citalopram 20-60 mg and risperidone 0.5-1 mg and were followed for 6 months. Twelve additional patients who denied treatment, or were non-compliant, were also followed for the same time period. Vascular function was assessed by flow-mediated dilatation (FMD), carotid-femoral pulse wave velocity (PWV) and augmentation index (AI), at baseline and at the end of follow-up.Aortic and peripheral blood pressure (BP), PWV, FMD and AI (p 0.05 for all) were significantly improved in the group that received treatment. Overall, only responders to treatment (n = 24) presented significant improvements in all hemodynamic and vascular parameters (p 0.05 for all), irrespectively of traditional cardiovascular risk factors (TRFs), vasoactive medication and BP lowering. In a secondary analysis, patients with psychotic depression presented worse endothelial function as compared to controls matched for TRFs.Non-randomized study.Patients who respond to therapy for major psychotic depression present sustained improvement in vascular function. Given that depressed patients are considered to be at high cardiovascular risk and are often non-compliant with treatment, further research to assess cardiovascular benefits of vigilant monitoring of antidepressant therapy is warranted.

Background: Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia globally and substantially increases the risk for thromboembolic disease. Albeit, 20% of all cases of AF remain undiagnosed. On the other hand, hypertension amplifies the risk for both AF occurrences through hemodynamic and non-hemodynamic mechanisms and cerebrovascular ischemia. Under this prism, prompt diagnosis of undetected AF in hypertensive patients is of pivotal importance. Method: We conducted a review of the literature for studies with biomarkers that could be used in AF diagnosis as well as in predicting the transition of paroxysmal AF to sustained AF, especially in hypertensive patients. Results: Potential biomarkers for AF can be broadly categorized into electrophysiological, morphological and molecular markers that reflect the underlying mechanisms of adverse atrial remodeling. We focused on P-wave duration and dispersion as electrophysiological markers, and left atrial (LA) and LA appendage size, atrial fibrosis, left ventricular hypertrophy and aortic stiffness as structural biomarkers, respectively. The heterogeneous group of molecular biomarkers of AF encompasses products of the neurohormonal cascade, including NT-pro BNP, BNP, MR-pro ANP, polymorphisms of the ACE and convertases such as corin and furin. In addition, soluble biomarkers of inflammation (i.e. CRP, IL-6) and fibrosis (i.e. TGF-1 and matrix metalloproteinases) were assessed for predicting AF. Conclusion: The reviewed individual biomarkers might be a valuable addition to current diagnostic tools but the ideal candidate is expected to combine multiple indices of atrial remodeling in order to effectively detect both AF and adverse characteristics of high risk patients with hypertension.

Progressive arterial stiffening, as a marker of arterial aging, may reach a plateau in elderly patients and may thus lose its clinical utility. This phenomenon may be more prominent in high-risk patients. We aimed to investigate if carotid-to-femoral pulse wave velocity (cf-PWV) is related to coronary artery disease (CAD) and diastolic dysfunction in elderly high-risk patients as compared to a control group of younger individuals.One-hundred and ninety-two high-risk stable patients who underwent coronary artery angiography and assessment of cf-PWV were consecutively recruited. Indices of diastolic dysfunction were also measured by echocardiography, including the volume of the left atrium and the ratio of early transmitral peak velocity (E) to the mitral annular early diastolic velocity (E').Increased cf-PWV was associated with the presence of CAD [odds ratio (OR) 1.34, P = 0.02], number of diseased coronary vessels (OR 1.17, P = 0.029) and CAD severity (P = 0.023) as assessed by Gensini score, in patients less than 65 years old after adjustment for traditional risk factors. Moreover, cf-PWV correlated with E/E' (P = 0.019) and increased the odds by 16% (OR 1.16, P = 0.048) for more severe diastolic dysfunction in patients aged below 65 years old. None of these outcomes correlated with cf-PWV in the elderly.In high cardiovascular risk patients, an age-dependent association of cf-PWV with CAD and diastolic dysfunction was evinced. In contrast to younger patients, these results suggest that measuring arterial stiffness in elderly high-risk patients may lack clinical value.

Background Significant differences are mentioned in the progress of calcification between aortic and mitral valve. Evidence of inflammation in calcific aortic and mitral valve disease suggests that pathways of Toll Like Receptors (TLR) and Interleukin (IL)-37 expression may contribute to this process. We sought to investigate the role of TLR-mediated inflammatory response and IL-37 pathway expression on aortic and mitral valve calcification. Material and methods One-hundred twenty stenotic valve cusps/leaflets (60 aortic, 60 mitral) were excised during surgery and were collected for histological, immunohistochemistry and morphometric analysis at our department. After total RNA isolation from a second part of valve cusps/leaflets, cDNA synthesis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) protocols were performed and relative mRNA levels of target genes were assessed. Results By histological analysis, the anti-inflammatory IL-37 levels were increased in mitral valve leaflets (MVL) compared to aortic valve cusps (AVCu) while all other biomarkers, including TLR, presented a reverse pattern with decreased levels as compared to AVCu. In terms of calcification biomarkers, only osteopontin differed between AVCu and MVL. mRNA analysis confirmed increased expression of IL-37 and decreased levels of TLR in MVL compared to AVCu. Conclusions Stenotic cusps of aortic valves express lower IL-37 and increased TLRs levels than stenotic mitral valve leaflets, suggesting a differential pro-calcification and pro-inflammatory profile between the two valves. This may explain the higher incidence of calcification of AVCu than MVL and offer therapeutic considerations.

Orthostatic hypotension (OH), that is blood pressure fall when standing from the supine to the erect position, is a common cardiovascular disorder, highly prevalent in elderly and frail individuals and in patients with multiple comorbidities. Orthostatic hypotension is considered a manifestation of dysfunction of the autonomic nervous system, caused or facilitated by several neurological or non-neurological diseases and conditions, while its clinical significance is increasingly recognized as a cause of impairment of quality of life and potentially of worse outcomes. Indeed, OH has been extensively studied and numerous prospective cohort studies support its association with adverse events, including coronary artery disease, heart failure, stroke, cognitive dysfunction, and, most importantly, mortality rates. Specific pharmacological and non-pharmacological interventions have been established for the treatment of OH. However, randomized data evaluating the impact of therapeutic interventions on morbidity and mortality outcomes are lacking. Thus, despite that OH seems to have important prognostic implications indicated by several reported associations with adverse events, it remains unclear whether OH treatment could improve prognosis. In the present review, we discuss the clinical applications associated with ΟΗ by outlining the current perspectives on ΟΗ definition, diagnosis, pathophysiology, prognostic role, and treatment.

BACKGROUND Sparse evidence of the prognostic benefit of the anti-inflammatory drug colchicine in chronic and acute coronary syndromes (CCS/ACS) exists. METHODS We performed a systematic search of studies on CCS or ACS comparing colchicine vs. placebo and reporting data on cardiovascular outcomes (primary end points of each study) and/or changes in hs-CRP. RESULTS Ten studies were selected: three on CCS (LoDoCo, LoDoCo2 and the CCS subgroup of COLCHICINE-PCI; total patient number = 6256), three on ACS (COLCOT, COPS, ACS subgroup of COLCHICINE-PCI; n = 5,654) and five (n = 532) on hs-CRP changes from 1 week to 12 months, in CCS and/or ACS. In patients with CCS, colchicine reduced by 49% risk of a composite end point (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.32 to 0.81, P = .005). The favourable effect of colchicine on the risk of cardiovascular events did not change when excluding COLCHICINE-PCI from analysis (HR 0.51, 95% CI 0.25 to 1.03, P = .061). In patients with ACS, the use of colchicine tended to decrease the occurrence of the combined end point compared with placebo (HR = 0.77, 95% CI 0.56 to 1.05, P = .100), and colchicine became significantly protective when removing COLCHICINE-PCI from analysis (HR = 0.72, 95% CI 0.56 to 0.92, P = .009). Furthermore, colchicine tended to reduce the hs-CRP increase (standardized mean difference=-0.31, 95% CI -0.72 to 0.1, P = .133) compared with placebo. CONCLUSIONS Colchicine therapy near halves the risk of cardiovascular events in CCS compared with placebo and is associated with a nonsignificant 23% risk reduction in ACS, together with a trend towards a greater reduction of hs-CRP.

Aims Reverse remodelling (RR) is the recovery from left ventricular (LV) dilatation and dysfunction. Many arbitrary criteria for RR have been proposed. We searched the criteria with the strongest prognostic yield for the hard endpoint of cardiovascular death. Methods and results We performed a systematic literature search of diagnostic criteria for RR. We evaluated their prognostic significance in a cohort of 927 patients with LV ejection fraction (LVEF) < 50% undergoing two echocardiograms within 12 +/- 2 months. These patients were followed for a median of 2.8 years (interquartile interval 1.3-4.9) after the second echocardiogram, recording 123 cardiovascular deaths. Two prognostic models were defined. Model 1 included age, LVEF, N-terminal pro-B-type natriuretic peptide, ischaemic aetiology, cardiac resynchronization therapy, estimated glomerular filtration rate, New York Heart Association, and LV end-systolic volume (LVESV) index, and Model 2 the validated Cardiac and Comorbid Conditions Heart Failure score. We identified 25 criteria for RR, the most used being LVESV reduction >= 15% (12 studies out of 42). In the whole cohort, two criteria proved particularly effective in risk reclassification over Model 1 and Model 2. These criteria were (i) LVEF increase >10 U and (ii) LVEF increase >= 1 category [severe (LVEF = 56%)]. The same two criteria yielded independent prognostic significance and improved risk reclassification even in patients with more severe systolic dysfunction, namely, those with LVEF < 40% or LVEF 10 U and LVEF increase >= 1 category displayed a greater prognostic value than LVESV reduction >= 15%, both in the whole cohort and in the subgroups with LVEF < 40% or LVEF 10 U independently predicted cardiovascular death over Model 1 and LVESV reduction >= 15% (hazard ratio 0.40, 95% confidence interval 0.18-0.90, P = 0.026), while LVESV reduction >= 15% did not independently predict cardiovascular death (P = 0.112). Conclusions Left ventricular ejection fraction increase >10 U and LVEF increase >= 1 category are stronger predictors of cardiovascular death than the most commonly used criterion for RR, namely, LVESV reduction >= 15%.

Myocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19–30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged

Evidence on nonfunctioning adrenal incidentaloma’s (NFAI) associated comorbidities and in particular, glucose disorders, is unclear in contrast to adrenal tumors with mild autonomous cortisol secretion. The current systematic review and meta-analysis aimed to assess the burden of impaired glucose metabolism including diabetes mellitus type 2 (T2DM), fasting blood glucose (FBG), and fasting blood insulin (FBI) levels in patients with NFAI and 1-mg overnight dexamethasone suppression test (ODST) ≤ 1.8 μg/dl across published studies. We searched PubMed, Cochrane, and Scopus databases for identifying studies published between 1956 and March 2021. Twenty-five studies met the selection criteria including prospective, retrospective, and case–control studies. Two reviewers independently extracted studies, participants’ characteristics and outcome data in a total pooled sample of 1548 patients. Patients with NFAI had twofold [(odds ratio (OR) (95% confidence interval (CI)): 2.03 (1.39–2.98)] increased odds to present T2DM as well as higher FBG [weighted mean difference (WMD) (95% CI): 3.85 (1.96–5.74)] and homeostasis model assessment (HOMA) [WMD (95% CI): 0.68 (0.23–1.12)] with respect to controls. On the contrary, the WMD of FBI levels did not differ between the two groups. The incidence of T2DM in a subgroup analysis of patients with NFAI without glucose disorders at baseline was 6% [pooled incidence (95% CI): 0.06 (0.04–0.09)]. Patients with NFAI and 1-mg ODST ≤ 1.8 μg/dl presented higher odds of T2DM and higher levels of FBG and HOMA index than healthy controls.

Aims Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P ≤ 0.003) and reclassification (P Conclusion This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.

Background Cardiac metastases of carcinoid tumours are extremely rare, and their diagnosis poses a significant challenge. A variety of techniques has been reported in the literature for this purpose, ranging from echocardiogram to the Indium-111 Octreotide, positron emission tomography using specific tracers, and biopsy. Occasionally, the diagnosis is only made post-mortem. Recently, CMR (cardiovascular magnetic resonance) has been added to the diagnostic toolkit. This case report describes the CMR sequences that can be used to characterize cardiac metastases of carcinoid tumours. Case summary A 55-year-old woman with an antecedent history of resected carcinoid tumour of the ileocecal junction underwent whole-body In-111 Octreoscan single-photon emission computed tomography in the context of her follow-up. This raised the suspicion of pericardial involvement, which prompted a CMR study. Comprehensive CMR findings were consistent with isolated carcinoid tumour metastasis embedded within the anterior papillary muscle. We describe the CMR sequences that were used to characterize the metastasis. Discussion The rarity of cardiac metastasis of carcinoid tumour makes its diagnosis challenging and warrants a high level of clinical suspicion. Cardiovascular magnetic resonance imaging proves to be an indispensable tool in the tissue characterization of such tumours.

Background Accumulating evidence suggests that circulating amyloidβ 1–40 (Αβ1–40), a proatherogenic aging peptide, may serve as a novel biomarker in cardiovascular disease (CVD). We aimed to explore the role of plasma Αβ1–40 and its patterns of change over time in atherosclerosis progression in postmenopausal women, a population with substantial unrecognized CVD risk beyond traditional risk factors (TRFs). Methods In this prospective study, Αβ1–40 was measured in plasma by enzyme-linked immunosorbent assay and atherosclerosis was assessed using carotid high-resolution ultrasonography at baseline and after a median follow-up of 28.2 months in 152 postmenopausal women without history or symptoms of CVD. Results At baseline, high Αβ1–40 was independently associated with higher carotid bulb intima-media thickness (cbIMT) and the sum of maximal wall thickness in all carotid sites (sumWT) (p Conclusion In postmenopausal women, a pattern of increasing or persistently high Αβ1–40 was associated with the rate of progression of subclinical atherosclerosis irrespective of its baseline levels. These findings provide novel insights into a link between Αβ1–40 and atherosclerosis progression in menopause and warrant further research to clarify the clinical value of monitoring its circulating levels as an atherosclerosis biomarker in women without clinically overt CVD.

Aims Observational studies suggest elevated blood pressure (BP) as the leading risk factor for incident atrial fibrillation (AF), but whether this relationship is causal remains unknown. In this study, we used Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of developing AF. Methods and results Genetic variants associated with the BP traits were retrieved from the International Consortium of Blood Pressure-Genome Wide Association Studies (N = 299 024). From 901 reported variants, 894 were assessed in a dedicated Genome-Wide Association Study of AF genetics, including >1 000 000 subjects of European ancestry. We used two-sample MR analyses to examine the potential causal association of systolic BP (SBP) and diastolic BP (DBP) as well as of pulse pressure (PP) with AF. MR analysis identified a potentially causal association between AF and SBP [odds ratio (OR): 1.018 per 1 mmHg increase, 95% confidence interval (CI): 1.012–1.024, P Conclusions The association between increased BP levels and the risk of AF is likely causal and applies for different BP indices. Independently from other risk factors, optimal BP control might represent an important therapeutic target for AF prevention in the general population.

Sacubitril/valsartan, vericiguat, and the sodium-glucose co-transporter-2 inhibitors (SGLT2i) dapagliflozin and empagliflozin proved effective in phase 3 trials on heart failure with reduced ejection fraction (HFrEF). We compared the treatment arms (sacubitril/valsartan, vericiguat, and SGLT2i) with the respective control arms (standard-of-care [SOC]) through a network meta-analysis of the phase 3 trials (PARADIGM-HF, VICTORIA, DAPA-HF, EMPEROR-Reduced), a phase 2 trial on vericiguat and the HFrEF subgroup of DECLARE-TIMI 58. There was a trend towards decreased risk of cardiovascular (CV) death or HF hospitalization with SGLT2i than sacubitril/valsartan (HR 0.92, 95% CI 0.81 to 1.05) and vericiguat (HR 0.83, 95% CI 0.73 to 0.94). A non-significant effect of SGLT2i on CV mortality compared to sacubitril/valsartan (HR 1.04, 95% CI 0.88 to 1.24) and vericiguat (HR 0.88, 95% CI 0.63 to 1.22) was found. SGLT2i demonstrated the greatest effect on HF hospitalization (HR 0.69, 95% CI 0.62 to 0.77) over the SOC, as well as a significant benefit over vericiguat (HR 0.77, 95% CI 0.66 to 0.89), but not over sacubitril/valsartan (HR 0.87, 95% CI 0.75 to 1.02). SGLT2i were ranked as the most effective therapy, followed by sacubitril/valsartan and vericiguat. Based on an indirect comparison, SGLT2i therapy is not associated with a significantly lower risk of CV death or HF hospitalization or CV death alone compared to sacubitril/valsartan or vericiguat. The risk of HF hospitalization does not differ significantly between patients on SGLT2i or sacubitril/valsartan, while dapagliflozin is superior to vericiguat. PROSPERO ID 186351.

Supplemental Digital Content is available in the text., Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institute of Health Stroke Scale was 10 (interquartile range [IQR], 4–18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institute of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4–18] versus 6 [IQR, 3–14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08–2.65] for higher National Institute of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2–6] versus 2 [IQR, 1–4], P

BACKGROUND: A considerable proportion of patients with atrial fibrillation (AF) are still treated with aspirin despite current guidelines due to presumed favorable safety.AIM: We performed a systematic review and meta-analysis of bleeding outcomes in randomized controlled trials (RCTs) comparing direct oral anticoagulants (DOACs) at doses approved for AF vs. aspirin.METHODS: We searched PubMed and Scopus for phase-III RCTs of DOACs at AF-approved doses vs. aspirin. Outcomes assessed were major-, intracranial-, gastrointestinal-, clinically-relevant-non-major- and fatal bleeding. We performed two subgroup analyses: one per patient population i.e. those at high risk of arterial or venous thromboembolism, and one per DOAC. We also performed a meta-regression to assess the association with patient age.RESULTS: In 4 eligible trials (20,440 patients) comparing DOACs vs. aspirin, the ORs were: 1.52 (95%CI: 0.91-2.53) for major bleeding in patients at high risk of arterial thromboembolism and 1.55 (95%CI:0.99-2.45, relative-risk-increase:55%, absolute-risk-increase:0.6%, number-needed-to-harm:170) in the overall analysis; 1.39 (95%CI:0.62-3.14) for intracranial bleeding in patients at high risk of arterial thromboembolism which was similar for the overall analysis; 1.27 (95%CI: 0.84-1.92) for gastrointestinal bleeding in patients at high risk of arterial thromboembolism and 1.26 (95%CI:0.86-1.85) in the overall analysis. Patient age was not a predictor of the magnitude of ORs for all bleeding outcomes.CONCLUSION: The present meta-analysis does not support the use of aspirin over DOACs in AF. Accordingly, the level of evidence of the related recommendations should be upgraded, which in turn may reduce further the proportion of AF patients treated with antiplatelets.

Oxygen is the most commonly used drug in emergency medicine. The aim of this study was to identify healthcare professionals’ preferences regarding oxygen therapy in common medical emergencies. An online 9-part-questionnaire was distributed through Facebook to doctors and nurses working in Greek hospitals. The questionnaire included background information of the respondents and addressed individual preferences regarding best oxygenation parameter and oxygen targets in specific acute settings. We received 678 responses and we included 663 in our analysis. We found significant differences between doctors’ and nurses’ attitudes towards oxygenation targets in ARDS, sepsis, acute coronary syndrome, and post cardiac-arrest patients. Nurses preferred a more conservative oxygen strategy compared to doctors. Furthermore, nurses favor SaO2 as the best oxygenation parameter, while doctors prefer PaO2. In our survey, the type of hospital and department of the respondents did not affect the preferred oxygen strategy. Social media-based survey research is feasible and effective. In this single country study, doctors showed a tendency to liberally administer oxygen in acutely ill medical patients. On the other hand, Greek nurses preferred a more conservative approach.

Objectives To assess differences in cardiac morphology and function in fetuses of mothers with gestational diabetes mellitus (GDM) compared to controls, and to assess whether, in women with GDM, fetal cardiac changes are accentuated with advancing gestational age. Methods We studied 112 women with GDM and 224 women with uncomplicated pregnancy at 24-40 weeks' gestation. In all fetuses, a standard four-chamber oblique view was obtained and offline speckle-tracking analysis was performed to measure right and left endocardial global longitudinal strain (GLS) and tricuspid and mitral annular plane systolic excursion. Global sphericity index was also calculated. Echocardiographic parameters were compared between GDM fetuses and controls at two gestational time periods of 24 + 0 to 32 + 0 weeks and 32 + 1 to 40 + 1 weeks. Results At 24 + 0 to 32 + 0 weeks, we phenotyped 43 fetuses from mothers with GDM and 71 from uncomplicated pregnancies, and, at 32 + 1 to 40 + 1 weeks, we phenotyped 69 fetuses from mothers with GDM and 153 from women with uncomplicated pregnancy. In fetuses of mothers with GDM, compared to controls, right ventricular functional indices were consistently lower both at 24 + 0 to 32 + 0 weeks and at 32 + 1 to 40 + 1 weeks. Right ventricular GLS was reduced in the GDM group at 24 + 0 to 32 + 0 weeks (adjusted mean difference, 0.7%; 95% CI, 0.3-1.1%) and at 32 + 1 to 40 + 1 weeks (adjusted mean difference, 0.9%; 95% CI, 0.6-1.1%). Fetal left ventricular global longitudinal function was similar in GDM pregnancies compared with controls, with the exception of the contractility of the left ventricular basal segment, which was reduced. Global sphericity index was reduced in GDM pregnancies only at 32 + 1 to 40 + 1 weeks (adjusted mean difference, -0.4; 95% CI, -0.7 to 0.1). Conclusions The offspring of women with GDM are at high risk for development of cardiovascular disease in childhood and early adulthood. Our study demonstrates that GDM is associated with a reduction mainly in fetal right ventricular function, compared to controls, and this response is not exaggerated with increasing gestational age. Further studies are needed to determine whether fetuses with the observed alterations in cardiac function are those at highest risk for subsequent development of cardiovascular disease. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Heart failure (HF) is recognized as a leading cause of morbidity and mortality worldwide. Dilated cardiomyopathy (DCM) is a common phenotype in patients presenting with HF. Timely diagnosis, appropriate identification of the underlying cause, individualized risk stratification, and prediction of clinical response to treatment have improved the prognosis of DCM over the last few decades. In this article, we reviewed the current evidence on available imaging techniques used for DCM patients. In this direction, we evaluated appropriate scenarios for the implementation of echocardiography, nuclear imaging, and cardiac computed tomography, and we focused on the primordial role that cardiac magnetic resonance (CMR) holds in the diagnosis, prognosis, and tailoring of therapeutic options in this population of special clinical interest. We explored the predictive value of CMR toward left ventricular reverse remodeling and prediction of sudden cardiac death, thus guiding the decisions for device therapy. Principles underpinning the use of state-of-the-art CMR techniques such as parametric mapping and feature-tracking strain analysis are also provided, along with expectations for the anticipated future advances in this field. We also attempted to correlate the evidence with clinical practice, with the intent to address questions on selecting the optimal imaging method for different indications and clinical needs. Overall, we recommend a comprehensive assessment of DCM patients at baseline and at follow-up intervals depending on the clinical status, with the addition of CMR as a second-line modality to other imaging techniques. We also provide an algorithm to guide the detailed imaging approach of the patient with DCM. We expect that future guidelines will upgrade their clinical recommendations for the utilization of CMR in DCM, which is expected to further improve the quality of care and the outcomes. This review provides an up-to-date perspective on the imaging of dilated cardiomyopathy patients and will be of clinical value to training doctors and physicians involved in the area of heart failure.

Objective: To evaluate the association between a personal history of lactation and indices of subclinical atherosclerosis in postmenopausal women.Methods: We evaluated the association between a his...

Preeclampsia at term accounts for half of maternal deaths from hypertensive disorders. We aimed to assess differences in maternal cardiac indices at 35 +0 to 36 +6 weeks’ gestation between women who subsequently developed preeclampsia at term compared with those with uncomplicated pregnancy and to evaluate whether cardiac indices offer incremental prognostic value to the available screening algorithm for preeclampsia. We recruited 1602 women with singleton pregnancies who attended for a routine hospital visit at 35 +0 to 36 +6 weeks’ gestation between April and November 2018. We recorded maternal characteristics and preeclampsia-risk-score derived from a competing risks model and measured cardiac indices. Preeclampsia developed in 3.12% (50/1602) of participants. Women with preeclampsia, compared with those without, had increased mean arterial pressure (97.6, SD, 5.53 versus 87.9, SD, 6.82 mm Hg), systemic vascular resistance (1500, interquartile range, 1393–1831 versus 1400, interquartile range, 1202–1630 PRU) and preeclampsia-risk-score (23.4, interquartile range, 9.13–40 versus 0.9, interquartile range, 0.32–3.25). Multivariable analysis demonstrated independent association between the incidence of preeclampsia and E/e′ (hazard ratio, 1.19/unit [95% CI, 1.03–1.37]; P =0.018) as well as left ventricular mass indexed for body surface area (hazard ratio, 1.03/[g·m 2 ] [95% CI, 1.003–1.051]; P =0.029). Women with E/e′ ≥7.3 and left ventricular mass indexed for body surface area ≥63.2 g/m 2 had an increased risk for developing preeclampsia, despite low preeclampsia-risk-score P

Anti-Müllerian hormone (AMH), which is secreted by granulosa cells of late preantral and small antral follicles, is a marker of ovarian reserve. The association of ovarian reserve with subclinical atherosclerosis in women of reproductive age is currently unknown. We primary investigated whether AMH levels are associated with markers of subclinical atherosclerosis in healthy, normally menstruating women. In this cross-sectional study, vascular structure and function were assessed by measurement of carotid and femoral intima–media thickness (IMT), flow-mediated dilation, carotid–femoral pulse wave velocity and augmentation index. Lipid profile and serum AMH concentrations were also measured. Seventy premenopausal women, aged 32.7 ± 6.5 years, were included. Mean AMH levels were lower in smokers than in non-smokers and negatively associated with total cholesterol (TC) levels. An inverse association between mean AMH concentrations and femoral and carotid IMT in all segments was observed. No correlation with other markers of subclinical atherosclerosis or established cardiovascular (CV) risk factors was found. After multivariable adjustment, the association between AMH concentrations and combined carotid IMT or carotid bulb IMT remained significant. In conclusion, in healthy, normally ovulating women, AMH concentrations are negatively associated with subclinical atherosclerosis indices and TC levels, independently of established CV risk factors.

Background Gestational diabetes mellitus is associated with early-onset cardiovascular disease and increased incidence of adverse cardiovascular outcomes in mothers and their offspring. Few studies with a limited number of patients have reported subclinical cardiac changes in association with gestational diabetes mellitus; however, it remains unclear whether the mother and the fetus respond in a similar fashion to gestational diabetes mellitus; thus, by assessing the heart of one, we can estimate or predict changes in the other. Objective This study aimed to compare maternal and fetal cardiovascular functions in the third trimester between women with gestational diabetes mellitus and women with uncomplicated pregnancy and to explore whether gestational diabetes mellitus affects to the same extent the maternal and fetal heart. Study Design This was a cross-sectional study of maternal and fetal echocardiography for assessment of cardiovascular function in the third trimester in women with singleton pregnancies who received a diagnosis of gestational diabetes mellitus and the control group with uncomplicated pregnancies. Results In this study, we included 161 women with gestational diabetes mellitus and 483 women with uncomplicated pregnancies. Compared with women in the control group, women with gestational diabetes mellitus were older (34.5, standard deviation, 5.3 years] vs 32.5, standard deviation, 4.8 years]; P Conclusion In the third trimester, in pregnancies with gestational diabetes mellitus, there were subclinical cardiac changes in both the mother and the fetus, but there was no significant difference in any of the fetal cardiac parameters between women with and women without unfavorable cardiac profile. This suggests that the stimulus for cardiovascular responses in the mother and fetus may not be the same in pregnancies with gestational diabetes mellitus.

Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21–1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146–2.97]; P P

Background: In-hospital cardiac arrest is a major cause of death in European countries, and survival of patients remains low ranging from 20% to 25%. Aims: The purpose of this study was to assess healthcare professionals’ knowledge on cardiopulmonary resuscitation among university hospitals in 12 European countries and correlate it with the return of spontaneous circulation rates of their patients after in-hospital cardiac arrest. Methods and results: A total of 570 healthcare professionals from cardiology, anaesthesiology and intensive care medicine departments of European university hospitals in Italy, Poland, Hungary, Belgium, Spain, Slovakia, Germany, Finland, The Netherlands, Switzerland, France and Greece completed a questionnaire. The questionnaire consisted of 12 questions based on epidemiology data and cardiopulmonary resuscitation training and 26 multiple choice questions on cardiopulmonary resuscitation knowledge. Hospitals in Switzerland scored highest on basic life support ( P=0.005) while Belgium hospitals scored highest on advanced life support ( PConclusion: Differences in knowledge about resuscitation and course attendance were found between university hospitals in 12 European countries. Education in cardiopulmonary resuscitation is considered to be vital for patients’ return of spontaneous circulation rates after in-hospital cardiac arrest. A higher level of knowledge in advanced life support results in higher return of spontaneous circulation rates.

Background Identification of reliable outcome predictors in coronavirus disease 2019 (COVID-19) is of paramount importance for improving patient's management. Methods A systematic review of literature was conducted until 24 April 2020. From 6843 articles, 49 studies were selected for a pooled assessment; cumulative statistics for age and sex were retrieved in 587 790 and 602 234 cases. Two endpoints were defined: (a) a composite outcome including death, severe presentation, hospitalization in the intensive care unit (ICU) and/or mechanical ventilation; and (b) in-hospital mortality. We extracted numeric data on patients' characteristics and cases with adverse outcomes and employed inverse variance random-effects models to derive pooled estimates. Results We identified 18 and 12 factors associated with the composite endpoint and death, respectively. Among those, a history of CVD (odds ratio (OR) = 3.15, 95% confidence intervals (CIs) 2.26-4.41), acute cardiac (OR = 10.58, 5.00-22.40) or kidney (OR = 5.13, 1.78-14.83) injury, increased procalcitonin (OR = 4.8, 2.034-11.31) or D-dimer (OR = 3.7, 1.74-7.89), and thrombocytopenia (OR = 6.23, 1.031-37.67) conveyed the highest odds for the adverse composite endpoint. Advanced age, male sex, cardiovascular comorbidities, acute cardiac or kidney injury, lymphocytopenia and D-dimer conferred an increased risk of in-hospital death. With respect to the treatment of the acute phase, therapy with steroids was associated with the adverse composite endpoint (OR = 3.61, 95% CI 1.934-6.73), but not with mortality. Conclusions Advanced age, comorbidities, abnormal inflammatory and organ injury circulating biomarkers captured patients with an adverse clinical outcome. Clinical history and laboratory profile may then help identify patients with a higher risk of in-hospital mortality.

To assess whether preoperative versus intraoperative insertion of an intra-aortic balloon pump is associated with lower 30-day mortality or reduced length of hospital stay among patients who had an intra-aortic balloon pump inserted for cardiac surgery.This was an observational study of patients who had an intra-aortic balloon pump inserted in the preoperative or intraoperative period of cardiac surgery in our department between 2000 and 2012. We assessed the association between preoperative versus intraoperative insertion of an intra-aortic balloon pump and 30-day mortality in a multivariable logistic regression analysis, including preoperative New York Heart Association class, postoperative atrial fibrillation, reoperation, postoperative creatinine and isolated coronary bypass grafting as cofactors. We used a multivariate linear model to assess whether a preoperative versus intraoperative intra-aortic balloon pump was associated with length of postoperative hospital stay, adjusting for reoperation, isolated coronary bypass grafting, heart valve surgery, sex, age, cardiopulmonary bypass time, aortic cross-clamp time, preoperative patients' status (elective, urgency or emergency surgery) and preoperative myocardial infarction.Overall, 7,540 consecutive patients underwent open heart surgery in our department, and an intra-aortic balloon pump was inserted pre- or intraoperatively in 322 (4.2%) patients. The mean age was 67 ± 10.2 years old, the 30-day mortality was 12.7%, and the median length of hospital stay was 9 days (7 - 13). Preoperative versus intraoperative intra-aortic balloon pump insertion did not affect the incidence of 30-day mortality (adjusted OR = 0.69; 95% CI, 0.15 - 3.12; p = 0.63) and length of postoperative hospital stay (β = 5.3; 95%CI, -1.6 to 12.8; p = 0.13).Preoperative insertion of an intra-aortic balloon pump was not associated with a lower 30-day mortality or reduced length of postoperative hospital stay compared to intraoperative insertion.Avaliar se o momento de inserção de um balão intra-aórtico pré-operatório em comparação com o intraoperatório se associa com menor mortalidade em 30 dias ou diminuição do tempo de permanência no hospital entre pacientes que passaram por inserção de um balão intra-aórtico para cirurgia cardíaca.Este foi um estudo observacional de pacientes submetidos à inserção de um balão intra-aórtico no período pré-operatório ou intraoperatório de cirurgia cardíaca em nosso departamento entre 2000 e 2012. Avaliamos a associação entre a inserção pré-operatória em comparação com a intraoperatória de um balão intra-aórtico e a mortalidade em 30 dias em uma análise de regressão logística multivariada, incluindo a classificação pré-operatória segundo a New York Heart Association, a presença de fibrilação atrial pós-operatória, a reoperação, a creatinina pós-operatória e a cirurgia de revascularização do miocárdio isolada como cofatores. Utilizamos um modelo linear multivariado para avaliar se a inserção pré-operatória do balão intra-aórtico, em comparação com a intraoperatória, associou-se com o tempo de permanência no hospital após a cirurgia, com ajuste para reoperação, cirurgia de revascularização do miocárdio isolada, cirurgia valvar, sexo, idade, tempo de bypass cardiopulmonar, tempo de oclusão aórtica, condição pré-operatória do paciente (cirurgia eletiva, de urgência ou emergência) e infarto do miocárdio pré-operatório.Foram submetidos à cirurgia cardíaca aberta em nosso departamento 7.540 pacientes consecutivos, tendo sido inserido um balão intra-aórtico em momento pré-operatório ou intraoperatório em 322 (4,2%) pacientes. A média de idade foi 67 ± 10,2 anos, e a mortalidade em 30 dias foi de 12,7%. O tempo mediano de permanência no hospital foi de 9 dias (7 - 13). A inserção pré-operatória de balão intra-aórtico, em comparação com a intraoperatória, não afetou a incidência de mortalidade em 30 dias (RC ajustada = 0,69; IC95% 0,15 - 3,12; p = 0,63) e nem o tempo de permanência no hospital após a cirurgia (β = 5,3; IC95% 1,6 - 12,8; p = 0,13).Em comparação com a inserção intraoperatória, a inserção pré-operatória de um balão intra-aórtico não se associou com menor mortalidade em 30 dias nem reduziu o tempo de permanência no hospital.

Preeclampsia (PE) continues to represent a worldwide problem and challenge for both clinicians and laboratory-based doctors. Despite many efforts, the knowledge acquired regarding its pathogenesis and pathophysiology does not allow us to treat it efficiently. It is not possible to arrest its progressive nature, and the available therapies are limited to symptomatic treatment. Furthermore, both the diagnosis and prognosis are frequently uncertain, whilst the ability to predict its occurrence is very limited. MicroRNAs are small non-coding RNAs discovered two decades ago, and present great interest given their ability to regulate almost every aspect of the cell function. A lot of evidence regarding the role of miRNAs in pre-eclampsia has been accumulated in the last 10 years. Differentially expressed miRNAs are characteristic of both mild and severe PE. In many cases they target signaling pathway-related genes that result in altered processes which are directly involved in PE. Immune system, angiogenesis and trophoblast proliferation and invasion, all fundamental aspects of placentation, are controlled in various degrees by miRNAs which are up- or downregulated. Finally, miRNAs represent a potential therapeutic target and a diagnostic tool.

Objectives: Accumulating evidence suggests a direct role of Uric Acid (UA) on Left Ventricular (LV) diastolic function in chronic kidney disease and Heart Failure (HF) patients. Recently, UA has been linked to LV Hypertrophy (LVH) and Diastolic Dysfunction (DD) in women with preserved Ejection Fraction (pEF) but not in corresponding men. We sought to assess if UA could predict indices of DD in hypertensive subjects with pEF independently of gender. Method: We consecutively recruited 382 apparently healthy hypertensive subjects (age: 61.7±10.7, women: 61.3%, median EF: 64%). In 318 patients in sinus rhythm, LV mass-indexed to body surface area-was calculated (LVMI). LVH was set as an LVMI >116g/m2 or 96 g/m2 in men and women, respectively. The ratio of early transmitral peak velocity (E) to the mitral annular early diastolic velocity (Em) was used as an approximation of mean left atrial pressure (E/Em). Results: UA [median (interquartile range): 5.4(2) mg/dl] independently predicted E/Em (adjusted coefficient: 1.01, p =0.026) while an interaction term between gender and UA was no significant (p=0.684). An ordinal score of DD was calculated taking into account increased E/Em, left atrium dilatation and LVH. Women with increased UA had 254% increased odds (adjusted OR=2.54, p=0.005) to be classified in the upper range of the DD score. Conclusion: In hypertensive subjects without HF, UA is independently associated with the presence of DD in both genders and correlates with its severity in women. Further prospective studies are warranted to evaluate the association of UA with adverse cardiovascular outcomes in high-risk populations such as HF with pEF.

Atrial fibrillation (AF) could be a coincidental finding in certain patients with ischemic stroke and increased burden of underlying cardiovascular disease. Concomitant large-vessel atheromatosis and cerebral small vessel disease may be the actual cause of stroke, and distinguishing between different pathophysiologic mechanisms could impose substantial diagnostic difficulties. Despite routine use of oral anticoagulants (OACs) in patients with AF based on their risk for embolism (ie, CHA2DS2-Vasc score), antithrombotic agents may exert differential effects depending on stroke etiology and stroke subtyping should be evaluated as an additional component of risk stratification that could facilitate optimal management. In the present study, we summarize the evidence on noncardioembolic (non-CE) stroke and treatment approaches based on different stroke subtypes in patients with AF. In particular, approximately one-third of patients with AF seem to suffer a non-CE stroke. Within this category, 11% to 24% of patients present high-grade carotid stenosis and 9% to 16% of ischemic strokes are classified as lacunar. In terms of secondary prevention, the effectiveness of OACs in preventing non-CE stroke has been disputed. Additional large-scale prospective studies are warranted to assess the pathophysiologic stroke mechanisms in patients with AF and compare the differential efficacy of antithrombotic treatment strategies in non-CE ischemic syndromes.

Genetic variations of genes encoding the endothelial nitric oxide synthase (eNOS) and the NADH/NADPH oxidase system are related with atherosclerosis in the general population, but their significance in women is not sufficiently assessed. We investigated the potential association between the G894T polymorphism of the NOS3 gene and the C242T polymorphism of the CYBA gene with subclinical vascular disease. Seventy (70) healthy, normally ovulating, premenopausal women were recruited for this study. Venous blood samples were obtained for biochemical/hormonal assessment as well as for genotyping, using real-time PCR. Sonographically assessed indices of vascular structure and function included carotid and femoral intima-media thickness (IMT), flow-mediated dilation (FMD), carotid-femoral pulse-wave velocity (PWV), and augmentation index. The prevalence of wild type, heterozygote, and homozygote genotype was 44.3% (31/70), 54.3% (38/70), and 1.4% (1/70) for the G894T polymorphism and 38.6% (27/70), 31.4% (22/70), and 30.0% (21/70) for the C242T polymorphism, respectively. After multivariable adjustment, the hC242T polymorphism was a predictor of both internal carotid IMT (b-coefficient - 0.119, p = 0.011) and combined-IMT (b-coefficient - 0.061, p = 0.015). Systolic blood pressure, lipids, and hC242T determined values of FMD (b-coefficient - 1.604, p = 0.034). Concerning the NOS3 G894T polymorphism, carriers of the polymorphic variant had higher values of IMT and PWV compared to the wild-type subgroup (carotid bulb-IMT and PWV, heterozygotes/homozygotes vs wild type 0.7 ± 0.2 vs 0.6 ± 0.1 mm; 7.1 ± 0.8 vs 6.6 ± 0.7 m/s; p = 0.048 and p = 0.029, respectively). These differences, however, were rendered non-significant in the multivariable analysis. In healthy premenopausal women, the CYBA C242T polymorphism is an independent determinant of endothelial function and subclinical atherosclerosis of the carotid arteries. The NOS3 G894T polymorphic variant also correlated with atherosclerosis, an association probably mediated by the traditional risk factors for CVD. The relevance of these findings in the clinical setting remains to be elucidated.