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Background/objectives Evidence regarding the influence of coffee on appetite and weight control is equivocal and the influence of covariates, such as genetic variation in caffeine metabolism, remains unknown. Herein, we addressed the novel hypothesis that genetic variation in CYP1A2, a gene responsible for more than 95% of caffeine metabolism, differentially impacts the association of coffee consumption with appetite and BMI among individuals with different genetic predispositions to obesity. Subjects/methods A cross-over randomized intervention study involving 18 volunteers assessed the effects of coffee consumption on dietary intake, appetite, and levels of the appetite-controlling hormones asprosin and leptin. Data on habitual coffee intake, BMI, and perceived appetite were obtained from an observational cohort of 284 volunteers using validated questionnaires. Participants were stratified according to a validated genetic risk score (GRS) for obesity and to the -163C > A (rs762551) polymorphism of CYP1A2 as rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers. Results Coffee consumption led to lower energy and dietary fat intake and circulating asprosin levels (P for interaction of rs762551 genotype*coffee consumption=0.056, 0.039, and 0.043, respectively) as compared to slow/intermediate metabolizers. High coffee consumption was more prevalent in rapid compared to slow metabolizers (P = 0.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption = 0.002 and 0.048, respectively). This differential association of rs762551 genotype and coffee consumption with BMI was more evident in individuals at higher genetic risk of obesity (mean adjusted difference in BMI = -5.82 kg/m2 for rapid versus slow/intermediate metabolizers who consumed more than 14 cups of coffee per week). Conclusions CYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. This association is more evident in subjects with high genetic predisposition to obesity. ClinicalTrials.gov: registered Clinical Trial NCT04514588.

Background and aimAlthough the diagnostic usefulness of high-sensitivity cardiac troponin T (hs-cTnT) is well established in ST-segment elevation myocardial infarction (STEMI), its prognostic relevance in risk stratification of patients with STEMI remains obscure. This study sought to determine the prognostic value of pre-reperfusion (admission) and post-reperfusion (12-hour) hs-cTnT in patients with STEMI treated with primary percutaneous coronary intervention (PPCI).MethodsRetrospective observational longitudinal study including consecutive patients with STEMI treated with PPCI at a university hospital in the northeast of England. hs-cTnT was measured at admission to the catheterisation laboratory and 12 hours after PPCI. Clinical, procedural and laboratory data were prospectively collected during patient hospitalisation (June 2010–December 2014). Mortality data were obtained from the UK Office of National Statistics. The study endpoints were in-hospital and overall mortality.ResultsA total of 3113 patients were included. Median follow-up was 53 months. Admission hs-cTnT >515 ng/L (fourth quartile) was independently associated with in-hospital mortality (HR=2.53 per highest to lower quartiles; 95% CI: 1.32 to 4.85; p=0.005) after multivariable adjustment for a clinical model of mortality prediction. Likewise, admission hs-cTnT >515 ng/L independently predicted overall mortality (HR=1.27 per highest to lower quartiles; 95% CI: 1.02 to 1.59; p=0.029). Admission hs-cTnT correctly reclassified risk for in-hospital death (net reclassification index (NRI)=0.588, pConclusionAdmission, but not 12-hour post-reperfusion, hs-cTnT predicts mortality and improves risk stratification in the PPCI era. These results support a prognostic role for admission hs-cTnT while challenge the cost-effectiveness of routine 12-hour hs-cTnT measurements in patients with STEMI.

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

Background Stroke incidence and case-fatality are reported to decline in high-income countries during the last decades. Epidemiological studies are important for health services to organize prevention and treatment strategies. Aims The aim of this population-based study was to determine temporal trends of stroke incidence and case-fatality rates of first-ever stroke in Arcadia, a prefecture in southern Greece. Methods All first-ever stroke cases in the Arcadia prefecture were ascertained using the same standard criteria and multiple overlapping sources in three study periods: from November 1993 to October 1995; 2004; and 2015–2016. Crude and age-adjusted to European population incidence rates were compared using Poisson regression. Twenty-eight days case fatality rates were estimated and compared using the same method. Results In total, 1315 patients with first-ever stroke were identified. The age-standardized incidence to the European population was 252 per 100,000 person-years (95% CI 231–239) in 1993/1995, 252 (95% CI 223–286) in 2004, and 211 (192–232) in 2015/2016. The overall age- and sex-adjusted incidence rates fell by 16% (incidence rates ratio 0.84, 95% CI: 0.72–0.97). Similarly, 28-day case-fatality rate decreased by 28% (case fatality rate ratio = 0.72, 95% CI: 0.58–0.90). Conclusions This population-based study reports a significant decline in stroke incidence and mortality rates in southern Greece between 1993 and 2016.

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.

Objectives Predicting serious infections (SI) in patients with rheumatoid arthritis (RA) is crucial for the implementation of appropriate preventive measures. Here we aimed to identify risk factors for SI and to validate the RA Observation of Biologic Therapy (RABBIT) risk score in real-life settings. Methods A multi-centre, prospective, RA cohort study in Greece. Demographics, disease characteristics, treatments and comorbidities were documented at first evaluation and one year later. The incidence of SI was recorded and compared with the expected SI rate using the RABBIT risk score. Results A total of 1557 RA patients were included. During follow-up, 38 SI were recorded [incidence rate ratio (IRR): 2.3/100 patient-years]. Patients who developed SI had longer disease duration, higher HAQ at first evaluation and were more likely to have a history of previous SI, chronic lung disease, cardiovascular disease and chronic kidney disease. By multivariate analysis, longer disease duration (IRR: 1.05; 95% CI: 1.005, 1.1), history of previous SI (IRR: 4.15; 95% CI: 1.7, 10.1), diabetes (IRR: 2.55; 95% CI: 1.06, 6.14), chronic lung disease (IRR: 3.14; 95% CI: 1.35, 7.27) and daily prednisolone dose ≥10 mg (IRR: 4.77; 95% CI: 1.47, 15.5) were independent risk factors for SI. Using the RABBIT risk score in 1359 patients, the expected SI incidence rate was 1.71/100 patient-years, not different from the observed (1.91/100 patient-years; P = 0.97). Conclusion In this large real-life, prospective study of RA patients, the incidence of SI was 2.3/100 patient-years. Longer disease duration, history of previous SI, comorbidities and high glucocorticoid dose were independently associated with SI. The RABBIT score accurately predicted SI in our cohort.

Aims Sacubitril/valsartan, dapagliflozin and vericiguat have shown a prognostic benefit in phase 3 trials on heart failure with reduced ejection fraction (HFrEF). Assessing their relative efficacy is an important goal. Methods and results We assessed the relative efficacy of dapagliflozin, sacubitril/valsartan and vericiguat, by comparing the treatment arms with the respective control arms (standard of care) through a network meta-analysis. The phase 3 trials (PARADIGM-HF, DAPA-HF, VICTORIA), the HFrEF subgroup of DECLARE-TIMI 58, and a phase 2 trial on vericiguat were evaluated. Dapagliflozin was associated with a non-significant reduction in the risk of cardiovascular (CV) death or HF hospitalization compared to sacubitril/valsartan (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.64 to 1.22) and vericiguat (HR 0.82, 95% CI 0.6 to 1.12). The risk of CV death did not differ significantly between patients on dapagliflozin or sacubitril/valsartan (HR 0.90, 95% CI 0.51 to 1.58), and between patients on dapagliflozin or vericiguat (HR 0.77, 95% CI 0.44 to 1.37). As for HF hospitalization, dapagliflozin conferred a significant benefit over vericiguat (HR 0.77, 95% CI 0.63 to 0.93), but not over sacubitril/valsartan (HR 0.87, 95% CI 0.72 to 1.06). Dapagliflozin was ranked as the most effective therapy, followed by sacubitril/valsartan and vericiguat. Conclusion Based on an indirect comparison, dapagliflozin 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 dapagliflozin or sacubitril/valsartan, while dapagliflozin is superior to vericiguat. Registration number PROSPERO ID 186351.

Aims 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. Methods and results 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. 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 meta-analysis of the diagnostic accuracy of CT vs. TEE. The pooled values of sensitivity and specificity were 97% (95% CI, 77-100%) and 94% (95% CI, 87-98%). The pooled DOR was 500 (95% CI, 52-4810), and the pooled LR+ and LR- values were 17% (95% CI, 7-40%) and 3% (95% CI, 0-28%). The shape of the HSROC curve and the 0.99 AUC suggested a high accuracy of CT vs. TEE. Conclusion TTE is a valid alternative to DE-CMR for the identification of LV thrombi, and CT has a good accuracy compared to TEE for the detection of LAA thrombosis.

This document presents the consensus recommendations of the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society for lipid modification in patients with ischemic stroke or transient ischemic attack. This clinical guide summarizes the current literature on lipid management and can be of assistance to the physicians treating stroke patients in clinical practice.

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 and aims Patients with embolic strokes of undetermined source (ESUS) usually present with mild symptoms. We aimed to compare the baseline characteristics between mild and severe ESUS, identify predictors for severe ESUS, and assess outcomes of patients with severe ESUS. Methods In the AF-ESUS (AF-ESUS) dataset, we stratified ESUS severity using the median National Institutes of Health Stroke Scale (NIHSS) score on admission as cut-off. We performed multivariable stepwise regression analyses to identify independent predictors of severe ESUS and to assess the association between ESUS severity and stroke recurrence, death, and new incident atrial fibrillation (AF) on follow-up. The 10-year cumulative probabilities of outcome incidence were estimated by the Kaplan–Meier product limit method. Results In 772 patients (median NIHSS: 6 (interquartile range: 3–12)), 414 (53.6%) patients had severe ESUS (i.e. NIHSS ≥6). Female sex was the only independent predictor for severe ESUS (odds ratio: 1.72 (1.27–2.33)). The rates of recurrence (3.3%/year vs. 3.4%/year, adjusted-hazard ratio: 1.09 (0.73–1.62)) and new incident AF (13.5% vs. 17.0%, adjusted odds ratio: 0.67 (0.44–1.03)) were similar between severe and mild ESUS, but mortality was higher (5.4%/year vs. 3.7%/year, adjusted-hazard ratio: 1.51 (1.05–2.16)) in severe ESUS. The 10-year cumulative probability for stroke recurrence was similar between severe and mild ESUS (38.1% (29.2–48.6) vs. 36.6% (27.8–47.0), log-rank test: 0.01, p = 0.920). The 10-year cumulative probability of death was higher in patients with severe ESUS compared with mild ESUS (40.5% (32.5–50.0) vs. 34.0% (26.0–43.6) respectively; log-rank test: 4.54, p = 0.033). Conclusions Women have more severe ESUS compared with men. Patients with severe ESUS have similar rates of stroke recurrence and new incident AF, but higher mortality compared with mild ESUS.

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.

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.

A 60-year-old patient presented with recalcitrant electrical storm (ES). Mild sedation and initial antiarrhythmic combination of esmolol and amiodarone did not affect the intensity of ES, which resulted in battery exhaustion. Oral propranolol in addition to intravenous amiodarone might be preferred in hemodynamically stable patients before interventional therapies. (Level of Difficulty: Intermediate.), Graphical abstract, A 60-year-old patient presented with recalcitrant electrical storm (ES). Mild sedation and initial anti-arrhythmic combination of esmolol and…

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

Background Black African/African-Caribbean individuals with hypertension (BH) are at greater risk of heart failure than those of white European ethnicity (WH). The mechanisms underlying this dissimilarity remain poorly understood. Purpose To investigate the influence of ethnicity on left ventricular (LV) remodelling using multi-parametric cardiovascular magnetic resonance (CMR). Methods BH (n=44), WH (n=38) and healthy-volunteers (HV; n=25, 5 of black ethnicity) underwent comprehensive CMR. The exam included: i) Arterial Stiffness/Afterload pulse-wave-velocity (PWV), aortic elastance (Ea) and systemic vascular resistance (SVR) by phase-contrast velocity-encoding imaging; ii) Ventricular remodelling/Function LV and right ventricular (RV) volumes, mass, ejection fraction (EF), LV peak-filling rate by short-axis cine images; myocardial strains were measured by feature tracking; iii) Left atrial (LA) remodelling/Function volumes and functions by long-axis cine images; iv) Tissue characterisation: extracellular volume by pre/post-contrast T1-mapping and late gadolinium enhancement (LGE) for interstitial and replacement myocardial fibrosis, respectively. Multivariate linear regression models were developed to investigate how LV remodelling associates with ethnicity, arterial afterload, including elastance (Ea) and stiffness [PW], and SVR. Models were adjusted for age, gender, body-mass-index, LV volumes or function and LA volumes. Results Subject characteristics are summarised in the Table. PWV and Ea and SVR were greater in hypertensives, particularly in BH, than HV; this was paralleled by higher LV mass, interventricular septum thickness (IVS), LA volumes but lower LV-EF. These findings were confirmed after adjusting for age. On the Model-1, IVS was associated with Ea (β=0.335, P=0.008) and black ethnicity (β=0.226, P=0.019) but not with SVR or PWV. For each increment of Ea there was a similar increase of IVS in BH and WH (P=0.602 for interaction), however BH had greater IVS than WH at each Ea value (Figure, fully-adjusted Model-1). On Model-2, LV end-diastolic volume was associated with Ea (β=−0.268, P=0.001), SVR (β=−0.319, P=0.019) but not with PWV or ethnicity. However, the inverse relation between LV size and Ea was significantly attenuated in BH (P=0.039 for interaction), (Figure, fully-adjusted Model-2). On model-3, LV-EF was associated with Ea (β=0.223, P=0.009) but not with ethnicity, PWV or SVR. LV-EF reduction for each Ea increment was similar for BH and WH (P=0.597 for interaction). Conclusion BH and WH show a distinctive LV remodelling phenotype. BH had a greater susceptibility to hypertrophy and an attenuated reduction of chamber size in response to arterial afterload. Further research to disentangle the genetic and environmental factors underlying these ethnic group-specific differences is utterly required. Funding Acknowledgement Type of funding sources: None. Figure 1Table 1

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 Radiofrequency catheter ablation remains the most effective management option for atrioventricular nodal reentry tachycardia (AVNRT). The risk of atrioventricular (AV) block requiring permanent pacemaker is substantial, but, currently, a reliable method to predict this complication is lacking. METHODS The electrophysiologic studies (EPS) and baseline characteristics of patients who underwent catheter ablation for the treatment of AVNRT were retrospectively analyzed to investigate predisposing factors for AV block after treatment. Patients were followed for AV block at one month and one year after hospital discharge. RESULTS Among 784 patients treated with catheter ablation for AVNRT between 1999 to 2019, 15 developed AV block. Patients with AV block were older (p = .001). Among the recorded EPS parameters, patients with AV block had significantly higher Atrial His interval (120 vs. 110 ms, p = .049), Wenckebach cycle length (WCL) (400 vs. 353 ms, p

Exercise has a deleterious effect on the phenotypic expression of arrhythmogenic right ventricular cardiomyopathy (ARVC) and increases the risk of sudden death. The aim of the study was to determine the prevalence and correlates of exercise-induced arrhythmias during exercise tolerance test (ETT) in patients with ARVC. Between 2010 and 2019, 30 (47% males, mean age 42 ± 12 years) consecutive patients with a definite diagnosis of ARVC underwent a full genotypic and phenotypic characterization at our center. Exercise-induced arrhythmic response (EIAR) was defined by the development of complex or repetitive ventricular arrhythmias after stage 2 of exercise. A heart rate ≥ 85% of predicted was achieved by 23 (77%) patients. In 16 (53%) cases, a desmosomal pathogenic variant was found [most commonly PKP2 (n = 7) and DSP (n = 3)]. In 12 (40%) cases, an EIAR was observed. In 2 (6%) patients, ETT was interrupted due to the onset of ventricular tachycardia (sustained with a LBBB/inferior axis pattern in one case, and non-sustained LBBB/superior axis pattern in the other). Mean body surface area (BSA)-indexed left ventricular (LV) end-diastolic volumes (EDV) were higher in the EIAR group (92 ± 12 ml/m2 vs 80 ± 7 ml/m2, p = 0.002), as well as right ventricular EDV/BSA (110 ± 18 ml/m2 vs 91 ± 27 ml/m2, p = 0.04). Subepicardial/mid-wall LV late gadolinium enhancement (LGE) was more common in the EIAR group (67% vs 22%, p = 0.01). ARVC patients commonly exhibit exercise-induced ventricular arrhythmias. Patients with more significant RV remodeling and LV involvement (based on the presence of LV dilatation and LGE) appear more susceptible to exercise-induced arrhythmias.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dr Georgiopoulos was supported by the Onassis Foundation under the special grant & support program for scholars" association members Introduction – Black Afro-Caribbean hypertensives (BAHs) are exposed to a higher risk of heart failure (HF) than white hypertensives (WHs). Arterial afterload is higher in BAHs due to increased arterial stiffness and vascular volume; BAHs develop more often left ventricular (LV) hypertrophy, dilatation and systolic dysfunction than WHs. However, it is unclear whether other racial differences concur to the more pronounced LV remodelling in BAHs. Methods – This cross-sectional study included hypertensive patients undergoing cardiovascular magnetic resonance for their clinical work-up (1.5T Aera Siemens-Healthcare). Clinical history and haemodynamic parameters were collected in all participants; a subset of patients had complete bio-humoral assay of the renin-angiotensin-aldosterone system (RAAs). Arm cuff pressure was measured during CMR. The CMR protocol included: i) Arterial afterload / LV arterial-coupling - pulse-wave-velocity (PWV), aortic (Ea) and LV elastance (Ees) by aorta anatomic and phase-contrast velocity-encoding imaging; ii) ventricular remodelling and function - LV and right ventricular (RV) volumes, mass, EF, LV peak-filling rate by short-axis cine images; global circumferential and longitudinal strains by cine feature tracking; iii) left atrial (LA) remodelling volumes and reservoir, conduit and booster functions by long-axis cine images; iv) tissue characterisation: T2 and pre/post-contrast T1 relaxation times, extracellular volume (ECV) by single mid-ventricular short-axis T1/T2-mapping. Results – 34 BAHs and 35 WHs (52 ± 12 vs 45 ± 14 years, P Conclusion – BAHs have heightened LV remodelling than WHs because of racial predisposition to develop hypertrophy which also encompasses derangements in RAAs. Altogether, these findings may account for the greater risk for HF in BAHs than WHs.

Funding Acknowledgements Type of funding sources: None. OnBehalf Mitral vAlve prolapse and disjunction by cardiac maGnetIC resonance (MA-GIC) registry Backgroung Mitral valve prolapse (MVP) is 2-3% prevalent in the general population with good prognosis. However, some patients develop complex ventricular arrhythmias (CVAs), sudden cardiac death (SCD), or severe mitral regurgitation (MR). Previous studies suggested that bi-leaflet involvement, mitral annulus disjunction (MAD), and myocardial fibrosis (MF) are associated with adverse outcome. Notwithstanding, these findings were limited to autopsic series or single-centre studies involving highly selected patients. Moreover, MF has been scantly investigated as predictor of clinical outcome. Purpose To investigate the prognostic significance of MF in an international multicentre study of MVP patients studied by cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Methods From October 2007 to June 2020 patients undergoing LGE-CMR were screened in 14 European centres. Inclusion criteria were: i) age > 18 years; ii) full clinical history and cardiac rhythm monitoring at baseline; iii) MVP (leaflet displacement ≥ 2 mm beyond the annulus). Exclusion criteria were: i) ischemic heart disease; ii) primary cardiomyopathy; iii) inflammatory heart disease; iv) congenital heart diseases; v) moderate-to-severe valvular heart disease. CVAs at the study outset was defined as one of the following: i) ventricular ectopic beats >10000/24h; ii) ≥ 1 episode of non-sustained ventricular tachycardia (VT); iii) sustained VT; iv) aborted SCD. Primary end-point was a composite of SCD, unexplained syncope, and mitral valve repair/replacement. Secondary end-point was a composite of SCD and unexplained syncope. Results Four-hundred-fifty-eight MVP patients were eventually included (46 ± 16 years old, 51% males) of whom 68% had MAD. LGE was detected in 103 (22%) of subjects with mid-wall pattern (46%) in left ventricular (LV) lateral wall (66%) as the most prevalent feature. At baseline, 37% of LGE-positive patients vs. 18% of LGE-negative individuals had CVAs (P Conlusion Myocardial fibrosis by LGE is the strongest independent predictor of clinical outcome in MVP. In contrast, MAD per se does not harbinger worse prognosis.

Introduction: We aimed to investigate the incidence of hypertension and to identify potential risk factors in healthy, non-diabetic recently postmenopausal Greek women with normal renal function.Pa...

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.