Publications by authors named "John Lekakis"

268 Publications

Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study.

Basic Res Cardiol 2021 02 6;116(1). Epub 2021 Feb 6.

2nd Department of Cardiology, Medical School, Attikon Hospital, National and Kapodistrian University of Athens, Rimini 1, Haidari, 12462, Athens, Greece.

Aims: Remote ischemic conditioning (RIC) alleviates ischemia-reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection.

Methods And Results: We block-randomised 270 patients within 48 h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: (a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; (b) the carotid-femoral pulse wave velocity (PWV); (c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 min after RIC onset (T3); and (d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p < 0.05) at T3 following single- than double-cycle inflation (PBR:ΔT0-T3 = 0.249 ± 0.033 vs 0.126 ± 0.034 μm, p = 0.03 and PWV:0.4 ± 0.21 vs -1.02 ± 0.24 m/s, p = 0.03). Increased miR-150,-21,-208 (p < 0.05) and reduced MDA was observed after both protocols. Increased miR-144 was related to PWV reduction (r = 0.763, p < 0.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV) > 15% (odds-ratio of 3.75, p = 0.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r = 0.40 and 0.37, p < 0.05), in the single-cycle RIC.

Conclusion: RIC evokes "vascular conditioning" likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling.

Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT03984123.
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http://dx.doi.org/10.1007/s00395-021-00851-1DOI Listing
February 2021

Optimal Blood Pressure Control Improves Left Ventricular Torsional Deformation and Vascular Function in Newly Diagnosed Hypertensives: a 3-Year Follow-up Study.

J Cardiovasc Transl Res 2020 10 2;13(5):814-825. Epub 2020 Jan 2.

Department of Echocardiography and Laboratory of Preventive Cardiology, 2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Rimini 1, Haidari, 12462, Athens, Greece.

We investigated the effects of optimizing blood pressure control on cardiac deformation and vascular function. For this purpose, in 200 untreated patients with essential hypertension, we assessed at baseline as well as after 3 years of optimal blood pressure control: arterial stiffness and coronary microcirculatory function as well as longitudinal and torsional deformation parameters. Compared to baseline, after 3 years of optimal blood pressure control, there was an improvement of longitudinal strain, twisting as well as untwisting parameters of the left ventricle. In parallel, there was an improvement in coronary microcirculatory function, arterial stiffness, left ventricular mass, and ventricular-arterial interaction. The reduction of arterial stiffness was independently associated with the respective improvement of cardiac deformation markers and coronary flow reserve after adjusting for blood pressure improvement. Blood pressure optimization improves LV longitudinal and torsional mechanics in hypertensives in parallel with arterial stiffness, resulting in improved ventricular-arterial interaction and coronary flow reserve. Trial registration: ClinicalTrials.gov Identifier: NCT02346695.
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http://dx.doi.org/10.1007/s12265-019-09951-9DOI Listing
October 2020

Effects of Different Antidiabetic Medications on Endothelial Glycocalyx, Myocardial Function, and Vascular Function in Type 2 Diabetic Patients: One Year Follow-Up Study.

J Clin Med 2019 Jul 5;8(7). Epub 2019 Jul 5.

2nd Department of Cardiology, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, 12462 Athens, Greece.

Background: Poor glycaemic control affects myocardial function. We investigated changes in endothelial function and left ventricular (LV) myocardial deformation in poorly controlled type 2 diabetics before and after glycaemic control intensification.

Methods: In 100 poorly-controlled diabetic patients (age: 51 ± 12 years), we measured at baseline and at 12 months after intensified glycaemic control: (a) Pulse wave velocity (PWV, Complior); (b) flow-mediated dilatation (FMD, %) of the brachial artery; (c) perfused boundary region (PBR) of the sublingual arterial micro-vessels (side-view dark-field imaging, Glycocheck); (d) LV global longitudinal strain (GLS), peak twisting (pTw), peak twisting velocity (pTwVel), and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography, where the ratio of PWV/GLS was used as a marker of ventricular-arterial interaction; and (e) Malondialdehyde (MDA) and protein carbonyls (PCs) plasma levels.

Results: Intensified 12-month antidiabetic treatment reduced HbA1c (8.9 ± 1.8% (74 ± 24 mmol/mol) versus 7.1 ± 1.2% (54 ± 14 mmol/mol), = 0.001), PWV (12 ± 3 versus 10.8 ± 2 m/s), PBR (2.12 ± 0.3 versus 1.98 ± 0.2 μm), MDA, and PCs; meanwhile, the treatment improved GLS (-15.2 versus -16.9%), PWV/GLS, and FMD% ( < 0.05). By multi-variate analysis, incretin-based agents were associated with improved PWV ( = 0.029), GLS ( = 0.037), PBR ( = 0.047), and FMD% ( = 0.034), in addition to a reduction of HbA1c. The patients with a final HbA1c ≤ 7% (≤ 53 mmol/mol) had greater reduction in PWV, PBR, and markers of oxidative stress, with a parallel increase in FMD and GLS, compared to those who had HbA1c > 7% (> 53 mmol/mol).

Conclusions: Intensified glycaemic control, in addition to incretin-based treatment, improves arterial stiffness, endothelial glycocalyx, and myocardial deformation in type 2 diabetes after one year of treatment.
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http://dx.doi.org/10.3390/jcm8070983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678085PMC
July 2019

The role of ventricular-arterial coupling in cardiac disease and heart failure: assessment, clinical implications and therapeutic interventions. A consensus document of the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association.

Eur J Heart Fail 2019 Apr 12;21(4):402-424. Epub 2019 Mar 12.

Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.

Ventricular-arterial coupling (VAC) plays a major role in the physiology of cardiac and aortic mechanics, as well as in the pathophysiology of cardiac disease. VAC assessment possesses independent diagnostic and prognostic value and may be used to refine riskstratification and monitor therapeutic interventions. Traditionally, VAC is assessed by the non-invasive measurement of the ratio of arterial (Ea) to ventricular end-systolic elastance (Ees). With disease progression, both Ea and Ees may become abnormal and the Ea/Ees ratio may approximate its normal values. Therefore, the measurement of each component of this ratio or of novel more sensitive markers of myocardial (e.g. global longitudinal strain) and arterial function (e.g. pulse wave velocity) may better characterize VAC. In valvular heart disease, systemic arterial compliance and valvulo-arterial impedance have an established diagnostic and prognostic value and may monitor the effects of valve replacement on vascular and cardiac function. Treatment guided to improve VAC through improvement of both or each one of its components may delay incidence of heart failure and possibly improve prognosis in heart failure. In this consensus document, we describe the pathophysiology, the methods of assessment as well as the clinical implications of VAC in cardiac diseases and heart failure. Finally, we focus on interventions that may improve VAC and thus modify prognosis.
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http://dx.doi.org/10.1002/ejhf.1436DOI Listing
April 2019

Differential effects of inhibition of interleukin 1 and 6 on myocardial, coronary and vascular function.

Clin Res Cardiol 2019 Oct 11;108(10):1093-1101. Epub 2019 Mar 11.

2nd Department of Cardiology, Medical School, Attikon Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Background: Anakinra, an interleukin-1 receptor antagonist and tocilizumab, an interleukin-6 receptor blocker, are used for the treatment of rheumatoid arthritis. We investigated the differential effects of anakinra and tocilizumab on myocardial and vascular function in an atherosclerosis model of patients with rheumatoid arthritis.

Methods: 120 patients with rheumatoid arthritis were randomized to anakinra (n = 40), tocilizumab (n = 40) or prednisolone (n = 40) for 3 months. Primary outcome measure was the change of left ventricular longitudinal strain after 3 months of treatment. Additionally, we measured coronary flow reserve, flow-mediated dilatation of the brachial artery, carotid-femoral pulse wave velocity, malondialdehyde and protein carbonyls as oxidative stress markers and C-reactive protein blood levels at baseline and post-treatment.

Results: At baseline, patients among the three treatment arms had similar age, sex, disease activity score and atherosclerotic risk factors. Compared with baseline, all patients had improved longitudinal strain (- 16% vs. - 17.8%), coronary flow reserve (2.56 vs. 2.9), malondialdehyde (2.0 vs. 1.5 µM/L), protein carbonyls (0.0132 vs. 0.0115 nmol/mg), and C-reactive protein post-treatment. In all patients, the percent decrease of malondialdehyde was correlated with percent increase of longitudinal strain (p < 0.001). Compared with tocilizumab and prednisolone, anakinra treatment resulted in a greater improvement of longitudinal strain (18.7% vs. 9.7% vs. 6%) and coronary flow reserve (29% vs. 13% vs. 1%), while pulse wave velocity and brachial blood pressure were improved only after tocilizumab treatment (11 ± 3 vs. 10.3 ± 2 m/s p < 0.05 for all comparisons).

Conclusions: Anakinra is associated with an improvement in cardiac function and tocilizumab with improvement in vascular function.

Clinical Trial Registration: URL: https:// http://www.clinicaltrials.gov . Unique identifier: NCT03288584.
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http://dx.doi.org/10.1007/s00392-019-01443-9DOI Listing
October 2019

Pulse wave velocity to global longitudinal strain ratio in hypertension.

Eur J Clin Invest 2019 Feb 19;49(2):e13049. Epub 2018 Dec 19.

2nd Department of Cardiology, Medical School, Attikon Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Background: Arterial elastance to left ventricular elastance ratio assessed by echocardiography is widely used as a marker of ventricular-arterial coupling.

Materials And Methods: We investigated whether the ratio of carotid-femoral pulse wave velocity, as a marker of arterial stiffness, to global longitudinal strain, as a marker of left ventricular performance, could be better associated with vascular and cardiac damage than the established arterial elastance/left ventricular elastance index. In 299 newly-diagnosed untreated hypertensives we measured, carotid-femoral pulse wave velocity, and carotid intima-media thickness, coronary-flow reserve, arterial elastance/left ventricular elastance, global longitudinal strain, and markers of left ventricular diastolic function (E/A and E') by echocardiography.

Results: Pulse wave velocity-to-global longitudinal strain ratio (PWV/GLS) was lower in hypertensives than controls (-0.61 ± 0.21 vs -0.45 ± 0.11 m/sec%, P < 0.001). Low PWV/GLS values were associated with carotid-intima media thickness > 0.9 mm (P = 0.003), E/A ≤ 0.8 (P = 0.019) and E' ≤ 9 cm/sec (P = 0.002) and coronary-flow reserve < 2.5 (P = 0.017), after adjustment for age, sex and mean arterial pressure. Low PWV/GLS was also associated with increased left ventricular mass and left atrial volume in the univariate (P = 0.003 and 0.038) but not in the multivariate model. In hypertensives, there was no significant association of arterial elastance-to-left ventricular elastance index with carotid intima media thickness, coronary flow reserve, E/A, E', or left atrial volume with the exception of an inverse association with left ventricular mass (P = 0.027).

Conclusions: Pulse wave velocity-to-global longitudinal strain ratio but not the echocardiography-derived arterial elastance-to left ventricular elastance index is related to impaired carotid-intima media thickness, coronary-flow reserve and diastolic function in hypertensives.
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http://dx.doi.org/10.1111/eci.13049DOI Listing
February 2019

HDL cholesterol levels and endothelial glycocalyx integrity in treated hypertensive patients.

J Clin Hypertens (Greenwich) 2018 11 13;20(11):1615-1623. Epub 2018 Oct 13.

2nd Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Attikon Hospital, Athens, Greece.

Endothelial dysfunction indicates target organ damage in hypertensive patients. The integrity of endothelial glycocalyx (EG) plays a vital role in vascular permeability, inflammation and elasticity, and finally to cardiovascular disease. The authors aimed to investigate the role of increased HDL cholesterol (HDL-C) levels, which usually are considered protective against cardiovascular disease, in EG integrity in older hypertensive patients. The authors studied 120 treated hypertensive patients older than 50 years were divided regarding HDL-C tertiles in group HDL (HDL-C ≥ 71 mg/dL, upper HDL-C tertile) and group HDL (HDL-C < 71 mg/dL, two lower HDL-C tertiles). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranging from 5 to 9 µm) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non-invasive accurate index of reduced EG thickness. PBR 5-9 was significantly decreased in group HDL (P = 0.04). In the whole population, HDL-C was inversely but moderately related to PBR 5-9 (r = -0.22, P = 0.01). In a multiple linear regression analysis model, using age, BMI, smoking habit, HDL-C, LDL-C, and office SBP, as independent variables, the authors found that BMI (β = 0.25, P = 0.006) independently predicted PBR 5-9 in the whole population. In older hypertensive patients, HDL-C ranging between 71 and 101 mg/dL might moderately protect EG and subsequently endothelial function. Future studies in several groups of low- or high-risk hypertensives are needed in order to evaluate the beneficial role of extremely elevated HDL-C regarding cardiovascular risk evaluation as well as endothelial glycocalyx as a novel index of target organ damage in essential hypertension.
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http://dx.doi.org/10.1111/jch.13404DOI Listing
November 2018

Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2018 05 8;20(5):853-872. Epub 2018 Mar 8.

Department of Internal Medicine, and Department of Research and Education, General Hospital Murska Sobota, Murska Sobota, Slovenia.

The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice. There are no specific limitations to HF treatment in T2DM. Subanalyses of trials addressing HF treatment in the general population have shown that all HF therapies are similarly effective regardless of T2DM. Concerning T2DM treatment in HF patients, most guidelines currently recommend metformin as the first-line choice. Sulphonylureas and insulin have been the traditional second- and third-line therapies although their safety in HF is equivocal. Neither glucagon-like preptide-1 (GLP-1) receptor agonists, nor dipeptidyl peptidase-4 (DPP4) inhibitors reduce the risk for HF hospitalization. Indeed, a DPP4 inhibitor, saxagliptin, has been associated with a higher risk of HF hospitalization. Thiazolidinediones (pioglitazone and rosiglitazone) are contraindicated in patients with (or at risk of) HF. In recent trials, sodium-glucose co-transporter-2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have both shown a significant reduction in HF hospitalization in patients with established CV disease or at risk of CV disease. Several ongoing trials should provide an insight into the effectiveness of SGLT2 inhibitors in patients with HFrEF and HFpEF in the absence of T2DM.
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http://dx.doi.org/10.1002/ejhf.1170DOI Listing
May 2018

Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives.

J Clin Hypertens (Greenwich) 2018 04 2;20(4):672-679. Epub 2018 Mar 2.

Second Cardiology Department, Attikon Hospital, Medical School National and Kapodistrian University of Athens, Athens, Greece.

We investigated the association of endothelial glycocalyx damage with arterial stiffness, impairment of coronary microcirculatory function, and LV myocardial deformation in 320 untreated hypertensives and 160 controls. We measured perfused boundary region (PBR) of the sublingual microvessels, a marker inversely related with glycocalyx thickness, coronary flow reserve (CFR), and Global Longitudinal strain (GLS) by echocardiography, pulse wave velocity (PWV), and central systolic blood pressure (cSBP). Hypertensives had higher PBR, PWV cSBP, and lower CFR and GLS than controls (P < .05). In hypertensives, increased PBR was associated with increased cSBP, PWV, and decreased CFR and GLS after adjustment for age, sex, BMI, smoking LV mass, heart rate, hyperlipidemia, and office SBP (P < .05). PBR had an additive value to PWV, CFR, and office SBP for the prediction of abnormal GLS (x = 2.4-3.8, P for change = .03). Endothelial glycocalyx is impaired in untreated hypertensives and is related to arterial stiffness, coronary, and myocardial dysfunction.
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http://dx.doi.org/10.1111/jch.13236DOI Listing
April 2018

Effects of 6-month treatment with the glucagon like peptide-1 analogue liraglutide on arterial stiffness, left ventricular myocardial deformation and oxidative stress in subjects with newly diagnosed type 2 diabetes.

Cardiovasc Diabetol 2018 01 8;17(1). Epub 2018 Jan 8.

2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Rimini 1 str, Haidari, 12462, Athens, Greece.

Background: Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM.

Methods: We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months. We measured at baseline and after 6-month treatment: (a) carotid-femoral pulse wave velocity (PWV) (b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw-Utw), at peak (%dpTw-Utw) and end of early LV diastolic filling (%dpTw-Utw) (c) Flow mediated dilatation (FMD) of the brachial artery and percentage difference of FMD (FMD%) (d) malondialdehyde (MDA), protein carbonyls (PCs) and NT-proBNP.

Results: After 6-months treatment, subjects that received liraglutide presented with a reduced PWV (11.8 ± 2.5 vs. 10.3 ± 3.3 m/s), MDA (0.92 [0.45-2.45] vs. 0.68 [0.43-2.08] nM/L) and NT-proBNP (p < 0.05) in parallel with an increase in GLS (- 15.4 ± 3 vs. - 16.6 ± 2.7), GLSR (0.77 ± 0.2 vs. 0.89 ± 0.2), pUtwVel (- 97 ± 49 vs. - 112 ± 52°, p < 0.05), %dpTw-Utw (31 ± 10 vs. 40 ± 14), %dpTw-Utw (43 ± 19 vs. 53 ± 22) and FMD% (8.9 ± 3 vs. 13.2 ± 6, p < 0.01). There were no statistically significant differences of the measured markers in subjects that received metformin except for an improvement in FMD. In all subjects, PCs levels at baseline were negatively related to the difference of GLS (r = - 0.53) post-treatment and the difference of MDA was associated with the difference of PWV (r = 0.52) (p < 0.05 for all associations) after 6-month treatment.

Conclusions: Six-month treatment with liraglutide improves arterial stiffness, LV myocardial strain, LV twisting and untwisting and NT-proBNP by reducing oxidative stress in subjects with newly diagnosed T2DM. ClinicalTrials.gov Identifier NCT03010683.
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http://dx.doi.org/10.1186/s12933-017-0646-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759220PMC
January 2018

Cangrelor in Percutaneous Coronary Intervention: Current Status and Perspectives.

J Cardiovasc Pharmacol Ther 2018 Jan 15;23(1):13-22. Epub 2017 Jun 15.

1 2nd Department of Cardiology, Attikon University Hospital, National and Capodistrian University of Athens Medical School, Athens, Greece.

Cangrelor is an intravenously administered P2Y receptor antagonist with very fast, potent, and quickly reversible action. In the CHAMPION PHOENIX trial, cangrelor provided an improved anti-ischemic protection compared with clopidogrel, without increasing the risk of severe bleeding. Cangrelor is currently approved by drug regulating authorities for patients undergoing percutaneous coronary intervention (PCI) without prior treatment with a P2Y receptor antagonist and not receiving a glycoprotein IIb/IIIa inhibitor, while its use is endorsed with a class IIb recommendation by the European Society of Cardiology guidelines. Several subanalyses of CHAMPION PHOENIX trial have tried to elucidate the role of cangrelor in PCI, including its usefulness during a 2-hour landmark analysis, impact on intraprocedural stent thrombosis, and reduction in myocardial infarction (MI) rate. The influence of gender, geographic region, access site, and bivalirudin use on cangrelor's effects has also been reported. In patients with ST elevation MI and in clinical scenarios of disturbed absorption of oral antiplatelet agents or in need of an intravenous agent, cangrelor may surpass oral agents' drawbacks. Transitioning to an oral agent is mandatory following cangrelor infusion discontinuation, although ticagrelor may be administered earlier without any pharmacodynamic interaction. Nevertheless, the clinical role of cangrelor in conjunction with administration of prasugrel or ticagrelor remains unclear. Accruing real-life experience is expected to improve our understanding of cangrelor's role in everyday clinical practice.
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http://dx.doi.org/10.1177/1074248417715004DOI Listing
January 2018

Coincidental ganglionated plexus modification during radiofrequency pulmonary vein isolation and post-ablation arrhythmia recurrence.

Europace 2017 Dec;19(12):1967-1972

2nd Department of Cardiology, National and Kapodistrean University of Athens Medical School, Attikon University Hospital, Athens, Greece.

Aims: Vagal responses (VR) during left atrial ablation for atrial fibrillation (AF) treatment have been reported to be associated with less recurrences, presumably because they are a sign of ganglionated plexi modification. Our objective was to evaluate whether coincidentally elicited VR during left atrial ablation are associated with lower AF recurrence rates.

Methods And Results: This is a post hoc analysis of a prospective study of 291 patients with paroxysmal AF undergoing radiofrequency pulmonary vein isolation (PVI). Vagal responses were defined as episodes of heart rate <40 bpm or asystole lasting >5 s elicited during energy application. Sixty-eight patients (23.4%) had a VR during ablation. In Kaplan-Meier analysis, mean recurrence-free survival was 449 days (95% confidence interval 411-488) in patients with VR when compared with 435 days (95% confidence interval 415-455) in those without (P = 0.310). The 12-month recurrence rate estimates were 25 and 27%, respectively. In an unadjusted Cox model, VR was associated with an odds ratio for recurrence of 0.77 (95% confidence interval 0.46-1.28).

Conclusion: Coincidentally elicited VR during radiofrequency PVI in patients with paroxysmal AF do not appear to be related to lower risk of arrhythmia recurrence. This may mean that, even if a VR is truly a sign of coincidental ablation of a ganglionated plexus, this does not necessarily mean that a therapeutic modification has been effected, at least to a degree associated with clinical benefit.
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http://dx.doi.org/10.1093/europace/euw309DOI Listing
December 2017

Percutaneous coronary intervention reduces mortality in myocardial infarction patients with comorbidities: Implications for elderly patients with diabetes or kidney disease.

Int J Cardiol 2017 Dec;249:83-89

CIBER Cardiovascular Diseases, Instituto de Salud Carlos III (ISCIII), Madrid, Spain; REGICOR Study Group, Cardiovascular Epidemiology and Genetics Group, Program of Epidemiology and Public Health, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Electronic address:

Background: Percutaneous coronary intervention (PCI) reduces mortality in most myocardial infarction (MI) patients but the effect on elderly patients with comorbidities is unclear. Our aim was to analyse the effect of PCI on in-hospital mortality of MI patients, by age, sex, ST elevation on presentation, diabetes mellitus (DM) and chronic kidney disease (CKD).

Methods: Cohort study of 79,791 MI patients admitted at European hospitals during 2000-2014. The effect of PCI on in-hospital mortality was analysed by age group (18-74, ≥75years), sex, presence of ST elevation, DM and CKD, using propensity score matching. The number needed to treat (NNT) to prevent a fatal event was calculated. Sensitivity analyses were conducted.

Results: PCI was associated with lower in-hospital mortality in ST and non-ST elevation MI (STEMI and NSTEMI) patients. The effect was stronger in men [Odds ratio (95% confidence interval) 0.30 (0.25-0.35)] than in women [0.46 (0.39-0.54)] aged ≥75years, and in NSTEMI [0.22 (0.17-0.28)] than in STEMI patients [0.40 (0.31-0.5)] aged <75years. PCI reduced in-hospital mortality risk in patients with and without DM or CKD (54-72% and 52-73% reduction in DM and CKD patients, respectively). NNT was lower in patients with than without CKD [≥75years: STEMI=6(5-8) vs 9(8-10); NSTEMI=10(8-13) vs 16(14-20)]. Sensitivity analyses such as exclusion of hospital stays <2days yielded similar results.

Conclusions: PCI decreased in-hospital mortality in MI patients regardless of age, sex, and presence of ST elevation, DM and CKD. This supports the recommendation for PCI in elderly patients with DM or CKD.
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http://dx.doi.org/10.1016/j.ijcard.2017.07.054DOI Listing
December 2017

Bilateral sphenopalatine ganglion block reduces blood pressure in never treated patients with essential hypertension. A randomized controlled single-blinded study.

Int J Cardiol 2018 Jan 16;250:233-239. Epub 2017 Oct 16.

2nd Cardiology Department, Medical School, University of Athens, ATTIKON Hospital, Athens, Greece.

Background: Sympathetic fibers connect sphenopalatine ganglion (SPG) with the central nervous system. We aimed to study the effect of SPG block in blood pressure (BP) in never treated patients with stage I-II essential hypertension.

Methods: We performed bilateral SPG block with lidocaine 2% in 33 hypertensive patients (mean age 48±12years, 24 men) and a sham operation with water for injection in 11 patients who served as the control group (mean age 51±12years, 8 men). All patients have been subjected to 24h ambulatory blood pressure monitoring prior and a month after the SBG block in order to estimate any differences in blood pressure parameters. We defined as responders to SBG block those patients with a 24h SBP decrease ≥5mmHg.

Results: We found that 24h and daytime DBP (p=0.02) as well as daytime DBP load (p=0.03) were decreased in the study group a month after SPG block. In addition, a significant response was noted in 12/33 responders (36%) regarding: a. SBP and DBP during overall 24h and daytime (p<0.001) and night-time periods, b. pre-awake and early morning SBP and c. SBP (daytime and night-time) and DBP (daytime) load. No differences regarding BP were found in the sham operation group.

Conclusions: SPG block is a promising, minimally invasive option of BP decrease in hypertensives, probably through SNS modulation. Additionally, due to its anesthetic effect, SPG block might act as a method of selection for those hypertensive patients with an activated SNS before any other invasive antihypertensive procedure.
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http://dx.doi.org/10.1016/j.ijcard.2017.10.042DOI Listing
January 2018

Combination antiplatelet treatment in coronary artery disease patients: A necessary evil or an overzealous practice?

Platelets 2018 May 12;29(3):228-237. Epub 2017 Oct 12.

a 2nd Department of Cardiology , Attikon University Hospital, National and Capodistrian University of Athens Medical School , Athens , Greece.

In seeking to improve care in coronary artery disease patients, further platelet inhibition has been occasionally applied beyond that provided by aspirin and a P2Y receptor antagonist. This review aims to offer insights about the rationale, the efficacy and safety of combination antiplatelet therapy, involving three or more agents. Overall, the use of glycoprotein (GP) IIb/IIIa inhibitors did not significantly modify the treatment effect of different antiplatelet strategies, including double vs standard clopidogrel, prasugrel vs clopidogrel, ticagrelor vs clopidogrel, cangrelor vs clopidogrel, and vorapaxar vs placebo. With the caveat that the use of GP IIb/IIIa inhibitor was not randomized, adding such an agent to aspirin and a P2Y receptor antagonist appears to carry a significantly increased bleeding potential. Moreover, adding vorapaxar to aspirin- and clopidogrel-treated patients is associated with more bleeding events, while the bleeding potential is further exacerbated in cases of quadruplicate antiplatelet treatment including aspirin, clopidogrel, vorapaxar, and a GP IIb/IIIa inhibitor. In ST-segment elevation, myocardial infarction patients' administration of an intravenous antiplatelet agent (GP IIb/IIIa inhibitor or cangrelor), in addition to aspirin and a P2Y receptor antagonist, efficiently bridges the pharmacodynamic gap of oral agents. Cilostazol on top of aspirin and clopidogrel appears to be safe, although of questionable clinical benefit. In conclusion, combination antiplatelet therapy should be reserved only for selected cases and following thoughtful consideration of the associated risk/benefit ratio.
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http://dx.doi.org/10.1080/09537104.2017.1353685DOI Listing
May 2018

Association of mineralocorticoid receptor antagonist use and in-hospital outcomes in patients with acute heart failure.

Clin Res Cardiol 2018 Jan 18;107(1):76-86. Epub 2017 Sep 18.

Heart Failure Unit, Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, 1 Rimini St, 12462, Athens, Greece.

Mineralocorticoid receptor antagonists (MRAs) constitute a beneficial therapy in chronic heart failure, but their use in the acute heart failure (AHF) setting remains rather unexplored. To assess the effect of MRAs administered during hospitalization on in-hospital outcomes of patients with AHF, we performed a post-hoc analysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF). Patients of the original study cohort (n = 4953) were categorized according to in-hospital MRA treatment status as MRA-treated (n = 1439) and untreated (n = 3514) subjects. Nearest-neighbor propensity score with 1:1 matching yielded a subsample of pairs of MRA-treated and MRA-untreated patients (n = 1003 in each treatment group) that were balanced in an extensive list of baseline characteristics. In-hospital mortality between MRA-treated and untreated patients were assessed by Cox regression analysis before and after adjustment for known prognostic factors and other concomitantly administered intravenous and oral HF specific therapies. In the matched cohort, in-hospital mortality was 4.2 vs 10.8% in MRA-treated vs untreated patients. Treatment with MRAs was associated with a reduction of in-hospital mortality [HR 0.372 (95% CI, 0.261-0.532), p < 0.001]. This association remained significant after adjustment for known prognostic factors and co-administered intravenous and oral HF therapies [HR: 0.618 (95% CI, 0.383-0.995), p = 0.048]. In conclusion, MRA therapy administered during hospitalization for AHF was associated with reduced in-hospital mortality. The role of MRAs in AHF deserves further examination in adequately powered randomized controlled studies.
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http://dx.doi.org/10.1007/s00392-017-1161-7DOI Listing
January 2018

Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis.

Circ Cardiovasc Imaging 2017 Sep;10(9)

From the Second Department of Cardiology (I.I., G.M., M.V., G.P., H.T., J.P., E.I., J.L.), Second Department of Dermatology and Venereology (E.P., K.T., D.R.), Department of Biological Chemistry (P.M., C.P.), and Department of Clinical Biochemistry (P.M., C.P.), Attikon Hospital, National and Kapodistrian University of Athens Medical School, Greece; and Department of Pharmaceutical Chemistry, National and Kapodistrian University of Athens School of Pharmacy, Greece (I.A., K.G.).

Background: Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis.

Methods And Results: One hundred fifty psoriasis patients were randomized to receive an anti-IL-12/23 (ustekinumab, n=50), anti-tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: -17.7% versus -19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-α, and IL-6 post-treatment (<0.05). Compared with anti-TNF-α and cyclosporine, anti-IL-12/23 treatment resulted in a greater improvement of global longitudinal strain (25% versus 17% versus 6%,), LV twist (27% versus 17% versus 1%), %untwMVO (31% versus 27% versus 17%), and coronary flow reserve (14% versus 11% versus 4%), as well as a greater reduction of IL-12 (-25% versus -4% versus -2%), malondialdehyde (-27% versus +5% versus +26%), and NT-proBNP(-26% versus -13.6% versus 9.1%) and increase of fetuin-a (<0.01). Pulse wave velocity and augmentation index were improved only after anti-IL-12/23 treatment and correlated with changes in global longitudinal strain, LV twisting-untwisting (<0.05).

Conclusions: In psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-α inhibition or cyclosporine treatment.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02144857.
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http://dx.doi.org/10.1161/CIRCIMAGING.117.006283DOI Listing
September 2017

Antiplatelet treatment in diabetic patients with acute coronary syndrome undergoing percutaneous coronary intervention: a GReek AntiPlatElet registry substudy.

Coron Artery Dis 2018 Jan;29(1):53-59

Department of Cardiology, Patras University Hospital, Patras.

Background And Aims: We compared the clinical outcome of diabetic versus nondiabetic patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the GReek AntiPlatElet (GRAPE) registry.

Patients And Methods: GRAPE is a prospective observational study, focusing on contemporary antiplatelet use in moderate-risk to high-risk ACS patients receiving PCI. Major adverse cardiovascular events (MACE), (composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium definition) at 1 year of follow-up were analyzed using propensity score adjustment. A subanalysis according to diabetes mellitus (DM) status was performed.

Results: Out of 2047 registered patients, 469 (22.9%) were diabetic. Complete 1-year follow-up was available in 95.1% of patients. MACE occurred in 12.2 and 7.2% of those patients with and without DM, respectively [adjusted hazard ratio (HR), 95% confidence interval (CI)=1.27 (0.89-1.79), P=0.2]. Observed BARC type ≥3 bleeding risk was not higher in diabetic patients: adjusted HR (95% CI)=1.20 (0.79-1.84). In the subgroup of clopidogrel-treated patients (N=238), MACE rate was significantly higher in diabetic compared with nondiabetic cohort [13.4 vs. 9%, adjusted HR (95% CI)=1.68 (1.07-2.64), P=0.03]. In the subgroup of ticagrelor-treated or prasugrel-treated patients (N=228), MACE rate did not differ significantly between diabetic and nondiabetic patients: 9.6 versus 5%, adjusted HR (95% CI)=1.35 (0.77-2.37), P=0.38.

Conclusion: In 'real-life' ACS undergoing PCI, diabetic patients have higher - although not significantly - MACE rate and no difference in bleeding events. This difference in MACE was significant among clopidogrel-treated patients, whereas when newer antiplatelet agents were used the negative impact of DM on ischemic events was eliminated.
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http://dx.doi.org/10.1097/MCA.0000000000000547DOI Listing
January 2018

Triple Antithrombotic Therapy in Atrial Fibrillation Patients Undergoing PCI: a Fading Role.

Cardiovasc Drugs Ther 2017 Jun;31(3):319-324

2nd Department of Cardiology, Attikon University Hospital, National and Capodistrian University of Athens Medical School, Rimini 1, Chaidari, 12462, Athens, Greece.

Triple antithrombotic therapy (TAT), consisting of aspirin, a P2Y receptor antagonist and oral anticoagulant (OAC) medication has been considered as an 'unavoidable' strategy for a 1-12 months for atrial fibrillation (AF) patients post acute coronary syndrome or percutaneous coronary angioplasty with stenting. However, TAT has rather poorly been adopted in real life practice, mainly because of an accompanying increased bleeding potential and lack of definitive results of randomized clinical trials. Several registries, meta-analyses and small randomized trials have so far provided the base of guidelines recommendations. Furthermore, in the recently published Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects with Atrial Fibrillation who Undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial involving 2124 patients, the primary safety endpoint of clinically significant bleeding was significantly reduced in the rivaroxaban low dose (15 mg daily) plus single P2Y receptor antagonist arm compared to TAT, with no difference in the secondary efficacy endpoint. Despite several limitations of the PIONEER AF-PCI trial, it appears that among patients who omit aspirin, there may be equivalent ischemic protection with dual therapy and no disadvantage for additional risk of thrombotic events.
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http://dx.doi.org/10.1007/s10557-017-6730-5DOI Listing
June 2017

Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program.

Atherosclerosis 2017 07 13;262:123-130. Epub 2017 May 13.

2nd Cardiology Department, Laboratory of Preventive Cardiology, Attikon Hospital, National and Kapodistrian University of Athens, Medical School, Greece.

Background And Aims: The effects of medically-aided smoking cessation on vascular function and oxidative stress are not fully clarified.

Methods: One hundred eighty-eight current smokers were randomized to varenicline or nicotine replacement treatment (NRT) for a 3-month period. We assessed: (a) augmentation index (Aix) and pulse wave velocity (PWV); (b) perfusion boundary region (PBR) of sublingual microvasculature (range:5-25 μm), an index of the endothelial glycocalyx thickness, using Sideview, Darkfield imaging; (c) the exhaled CO; and (d) the malondialdehyde (MDA) and protein carbonyls (PC) plasma levels, as markers of oxidative stress, at baseline and after 3 and 12 months.

Results: After 3 months of treatment, CO, MDA, PC and Aix were decreased in all subjects (median CO: 25 vs. 6 ppm, MDA: 0.81 vs. 0.63 nmol/L, PC: 0.102, vs. 0.093 nmol/mg protein, Aix: 13% vs. 9%, p < 0.05) while PWV remained unchanged. Endothelial glycocalyx integrity showed a greater improvement in the varenicline than the NRT treatment (PBR range 5-9 μm: 1.07 ± 0.02 vs. 1.17 ± 0.02 μm, p = 0.03) in parallel with the greater CO reduction (5 vs. 7 ppm, p = 0.02). At 1-year follow-up, MDA, PC, Aix and PBR at 5-25 μm range were further improved in subjects who abstained from smoking (n = 84 out of 188), while the above markers and PWV deteriorated in relapsed smokers (p < 0.05).

Conclusions: A smoking cessation program using varenicline or NRT for 3 months resulted in a decrease of CO, oxidative stress, arterial stiffness and restored endothelial glycocalyx. These effects were more evident after varenicline treatment, likely because of a greater CO reduction, and were maintained after 1 year only in subjects who abstained from smoking.
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http://dx.doi.org/10.1016/j.atherosclerosis.2017.05.012DOI Listing
July 2017

Gender-related differences in antiplatelet treatment patterns and outcome: Insights from the GReekAntiPlatElet Registry.

Cardiovasc Ther 2017 Aug;35(4)

Department of Cardiology, Patras University Hospital, Patras, Greece.

Aims: Data on the clinical impact of gender in "real-life" patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), receiving clopidogrel, prasugrel, or ticagrelor are limited. We aimed to investigate sex-based differences in clinical outcome of those patients.

Methods: In a prospective, observational, multicenter, cohort study, 2047 patients were recruited into the GReekAntiPlatElet (GRAPE) Registry and were followed up until 1 year for major adverse cardiovascular events (MACE, composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] classification).

Results: Women (n=360, 17.6%) were more frequently administered clopidogrel (rather than novel P2Y receptor antagonists) at PCI hospital and at discharge. MACE occurred in 9.2% and 8.1% of women and men, respectively and did not differ significantly by gender. Rate of observed bleeding BARC any type was 57.2% and 44.4% in women and men, respectively. Following adjustment, only differences in BARC any type and BARC type 1 events remained significant, with higher rates observed between women: hazard ratio (95% confidence interval) 1.51 (1.23-1.85) and 1.58 (1.27-1.96), respectively, P<.001 for both.

Conclusions: In a contemporary "real-life" cohort of patients with ACS treated with PCI and focusing on antiplatelet treatment 1-year ischemic outcome does not differ by gender, while women do present more frequently not actionable bleeding events.
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http://dx.doi.org/10.1111/1755-5922.12270DOI Listing
August 2017

Duration of paroxysmal atrial fibrillation in cryptogenic stroke is not associated with stroke severity and early outcomes.

J Neurol Sci 2017 May 23;376:191-195. Epub 2017 Mar 23.

Second Department of Neurology, "Attikon" Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece. Electronic address:

The current definition of paroxysmal atrial fibrillation (PAF) requires an arbitrary cut-off of >30s, but in clinical practice cryptogenic stroke (CS) patients with PAF duration of ≤30s are not usually excluded from anticoagulation therapy. We sought to evaluate the clinical relevance of short-duration (≤30s) PAF in CS. Consecutive CS patients with no prior AF history and sinus-rhythm on baseline electrocardiography (ECG) were prospectively evaluated over a three-year period. Baseline stroke severity was assessed by NIHSS-scores. All patients underwent 24-hour Holter-ECG during hospitalization. ECG recordings were analyzed by two blinded investigators using dedicated analysis software. Total time in AF was calculated as the sum of each individual AF episode for patients with multiple episodes during monitoring. Patients were dichotomized in two groups using PAF total duration (≤30s & >30s). Early recurrent stroke and favorable functional outcome (FFO, defined as mRS-grades of 0-1) were evaluated during a three-month follow-up period. A total of 184 patients (66% men, mean age 57±11years) with CS (median NIHSS-score 4, IQR: 2-7) were evaluated. PAF of any duration was detected in 23 individuals (13%; 95%CI: 8%-18%). Among these patients the prevalence of brief PAF was 57% (n=13). The two groups did not differ (p>0.2) in terms of demographics, vascular risk factors and NIHSS-scores. Early recurrent stroke and FFO rates were similar (p>0.4) in the two groups. Duration of PAF is not associated with baseline stroke severity and early outcomes in patients with CS and should not influence anticoagulation decision in these patients.
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http://dx.doi.org/10.1016/j.jns.2017.03.038DOI Listing
May 2017

Short-term effects of Mediterranean-type diet intervention on soluble cellular adhesion molecules in subjects with abdominal obesity.

Clin Nutr ESPEN 2017 Feb 23;17:38-43. Epub 2016 Dec 23.

Unit of Human Nutrition, Department of Food Science and Human Nutrition, Agricultural University of Athens, Greece. Electronic address:

Background & Aims: Abdominal obesity (AO) is associated with increased risk for cardiovascular disease and with increased production of adhesion molecules. The present work examined the effect of a Mediterranean-style diet on soluble cellular adhesion molecules in individuals with AO.

Methods: Ninety subjects with AO without cardiovascular disease or diabetes mellitus were randomly allocated to the intervention or control group and were instructed to follow a Mediterranean-style diet for two months. Intervention group followed a specific relevant food plan with close dietetic supervision and provision of basic foods. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), sP and sE-selectin, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured.

Results: Subjects in the intervention group increased their intake of total fat, monounsaturated fatty acids, dietary fiber, vitamin C, and alcohol compared to controls, while decreased their intake of saturated fat. Although there was a significant decrease in CRP, sP-selectin and in sE-selectin in the intervention group, and an increase in sVCAM-1 in the control group, between-group analysis showed no statistically significant differences. There were also no significant changes in sICAM-1, and IL-6 levels after intervention.

Conclusions: Mediterranean-type diet for two months combined with close dietetic supervision showed a beneficial tendency towards the down-regulation of some markers of vascular inflammation, although the comparison between groups after the intervention did not reach statistical significance. A longer period of dietary intervention may be required to further support these changes.
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http://dx.doi.org/10.1016/j.clnesp.2016.11.002DOI Listing
February 2017

Independent academic Data Monitoring Committees for clinical trials in cardiovascular and cardiometabolic diseases.

Eur J Heart Fail 2017 04 8;19(4):449-456. Epub 2017 Mar 8.

Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Centre Göttingen (UMG), Robert-Koch-Strasse 40, D-37075, Göttingen, Germany.

Data Monitoring Committees (DMCs) play a crucial role in the conducting of clinical trials to ensure the safety of study participants and to maintain a trial's scientific integrity. Generally accepted standards exist for DMC composition and operational conduct. However, some relevant issues are not specifically addressed in current guidance documents, resulting in uncertainties regarding optimal approaches for communication between the DMC, steering committee, and sponsors, release of information, and liability protection for DMC members. The Heart Failure Association (HFA) of the European Society of Cardiology (ESC), in collaboration with the Clinical Trials Unit of the European Heart Agency (EHA) of the ESC convened a meeting of international experts in DMCs for cardiovascular and cardiometabolic clinical trials to identify specific issues and develop steps to resolve challenges faced by DMCs.The main recommendations from the meeting relate to methodological consistency, independence, managing conflicts of interest, liability protection, and training of future DMC members. This paper summarizes the key outcomes from this expert meeting, and describes the core set of activities that might be further developed and ultimately implemented by the ESC, HFA, and other interested ESC constituent bodies. The HFA will continue to work with stakeholders in cardiovascular and cardiometabolic clinical research to promote these goals.
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http://dx.doi.org/10.1002/ejhf.761DOI Listing
April 2017

The independent association of two "priceless" parameters: Pulse pressure and red cell distribution width in recently diagnosed hypertensive patients.

Hellenic J Cardiol 2016 Nov - Dec;57(6):459-462. Epub 2016 Nov 17.

2(nd) Department of Cardiology Medical School, University of Athens, ATTIKON Hospital, Athens, Greece.

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http://dx.doi.org/10.1016/j.hjc.2016.11.018DOI Listing
January 2018
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