Publications by authors named "Konstantinos Katogiannis"

19 Publications

  • Page 1 of 1

Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial deformation 4 months after infection.

Eur J Heart Fail 2021 Aug 20. Epub 2021 Aug 20.

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

Aims: SARS-CoV-2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers 4 months after COVID-19 infection.

Methods And Results: In a case-control prospective study, we included 70 patients 4 months after COVID-19 infection, 70 age- and sex-matched untreated hypertensive patients (positive control) and 70 healthy individuals. We measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV), (v) global left and right ventricular longitudinal strain (GLS), and (vi) malondialdehyde (MDA), an oxidative stress marker, thrombomodulin and von Willebrand factor as endothelial biomarkers. COVID-19 patients had similar CFR and FMD as hypertensives (2.48 ± 0.41 vs. 2.58 ± 0.88, P = 0.562, and 5.86 ± 2.82% vs. 5.80 ± 2.07%, P = 0.872, respectively) but lower values than controls (3.42 ± 0.65, P = 0.0135, and 9.06 ± 2.11%, P = 0.002, respectively). Compared to controls, both COVID-19 and hypertensives had greater PBR5-25 (2.07 ± 0.15 µm and 2.07 ± 0.26 µm, P = 0.8 vs. 1.89 ± 0.17 µm, P = 0.001), higher PWV (carotid-femoral PWV 12.09 ± 2.50 vs. 11.92 ± 2.94, P = 0.7 vs. 10.04 ± 1.80 m/s, P = 0.036) and impaired left and right ventricular GLS (-19.50 ± 2.56% vs. -19.23 ± 2.67%, P = 0.864 vs. -21.98 ± 1.51%, P = 0.020 and -16.99 ± 3.17% vs. -18.63 ± 3.20%, P = 0.002 vs. -20.51 ± 2.28%, P < 0.001). MDA and thrombomodulin were higher in COVID-19 patients than both hypertensives and controls (10.67 ± 0.32 vs 1.76 ± 0.03, P = 0.003 vs. 1.01 ± 0.05 nmol/L, P = 0.001 and 3716.63 ± 188.36 vs. 3114.46 ± 179.18 pg/mL, P = 0.017 vs. 2590.02 ± 156.51 pg/mL, P < 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress and endothelial dysfunction markers.

Conclusions: SARS-CoV-2 may cause endothelial and vascular dysfunction linked to impaired cardiac performance 4 months after infection.
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http://dx.doi.org/10.1002/ejhf.2326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426810PMC
August 2021

Effects of hormone replacement therapy on endothelial function, arterial stiffness and myocardial deformation in women with Turner syndrome.

J Hypertens 2021 Oct;39(10):2051-2057

2nd Department of Cardiology.

Objectives: Turner syndrome (TS) is associated with increased cardiovascular risk. We investigated whether hormone replacement therapy (HRT) affects endothelial function, arterial stiffness and myocardial deformation in women with TS.

Methods: Twenty-five women with TS were studied in the estrogen phase of the HRT and two months after discontinuation of HRT. The following measurements were made: flow-mediated dilation (FMD) of the brachial artery, pulse wave velocity (PWV-Complior) and central systolic blood pressure (cSBP), carotid intima-media thickness (cIMT), aortic (Ao) elastic indexes - namely Ao strain, distensibility, stiffness index and pressure strain modulus (Ep) - and left ventricular (LV) global longitudinal strain (GLS) using speckle-tracking echocardiography. Ten healthy female of similar age and BMI served as a control group.

Results: Compared to controls, women with TS on HRT had higher PWV (9.1 ± 2.4 vs. 7.5 ± 0.5 m/s), cSBP (130 ± 15 vs. 121 ± 6 mmHg), cIMT (0.66 ± 0.06 vs. 0.55 ± 0.05 mm), aortic stiffness index, Ep and LA strain, and lower FMD (7.2 ± 4 vs. 10.5 ± 2.3%), Ao strain, Ao distensibility and GLS (-18.8 ± 2.7 vs. -21.9 ± 1.5%) (P < 0.05 for all comparisons). Two months after discontinuation of HRT, all women increased FMD (11.7 ± 6 vs. 7.2 ± 4%) and reduced PWV (7.8 ± 1.7 vs. 9.1 ± 2.4 m/s) and cSBP (123 ± 14 vs. 130 ± 15 mmHg). There were no statistically significant changes in BMI, cIMT and GLS (P > 0.05 for all comparisons). The percentage decrease of cSBP was associated with the percentage decrease of PWV (r = 0.54) and reversely related with the percentage increase of FMD (r = -0.57; P < 0.05 for all comparisons).

Conclusions: HRT in women with TS may deteriorate endothelial function contributing to increased arterial stiffness and central arterial blood pressure.
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http://dx.doi.org/10.1097/HJH.0000000000002903DOI Listing
October 2021

Differential effects of heat-not-burn and conventional cigarettes on coronary flow, myocardial and vascular function.

Sci Rep 2021 Jun 3;11(1):11808. Epub 2021 Jun 3.

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

We compared the effects of Heat-not-Burn cigarette (HNBC) to those of tobacco cigarette (Tcig), on myocardial, coronary and arterial function as well as on oxidative stress and platelet activation in 75 smokers. In the acute study, 50 smokers were randomised into smoking a single Tcig or a HNBC and after 60 min were crossed-over to the alternate smoking. For chronic phase, 50 smokers were switched to HNBC and were compared with an external group of 25 Tcig smokers before and after 1 month. Exhaled carbon monoxide (CO), pulse wave velocity (PWV), malondialdehyde (MDA) and thromboxane B2 (TxB2) were assessed in the acute and chronic study. Global longitudinal strain (GLS), myocardial work index (GWI), wasted myocardial work (GWW), coronary flow reserve (CFR), total arterial compliance (TAC) and flow-mediated dilation (FMD) were assessed in the chronic study. Acute HNBC smoking caused a smaller increase of PWV than Tcig (change 1.1 vs 0.54 m/s, p < 0.05) without change in CO and biomarkers in contrast to Tcig. Compared to Tcig, switching to HNBC for 1-month improved CO, FMD, CFR, TAC, GLS, GWW, MDA, TxB2 (differences 10.42 ppm, 4.3%, 0.98, 1.8 mL/mmHg, 2.35%, 19.72 mmHg%, 0.38 nmol/L and 45 pg/mL respectively, p < 0.05). HNBCs exert a less detrimental effect on vascular and cardiac function than tobacco cigarettes.Trial registration Registered on https://clinicaltrials.gov/ (NCT03452124, 02/03/2018).
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http://dx.doi.org/10.1038/s41598-021-91245-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175445PMC
June 2021

Echocardiography, an Indispensable Tool for the Management of Diabetics, with or without Coronary Artery Disease, in Clinical Practice.

Medicina (Kaunas) 2020 Dec 18;56(12). Epub 2020 Dec 18.

Second Department of Internal Medicine, 'Attikon University Hospital', Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.

Diabetes mellitus is a major factor contributing to the development of cardiovascular disease. As morbidity and mortality rates rise dramatically, when target organ damage develops pre-symptomatic assessment is critical for the management of diabetic patients. Echocardiography is a noninvasive and reproducible method that may aid in risk stratification and in evaluation of treatment effects. The aim of this review is to analyze the echocardiographic techniques which can detect early alteration in cardiac function in patients with diabetes.
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http://dx.doi.org/10.3390/medicina56120709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767240PMC
December 2020

Effects of electronic cigarette on platelet and vascular function after four months of use.

Food Chem Toxicol 2020 Jul 25;141:111389. Epub 2020 Apr 25.

Laboratory of Haematology & Blood Bank Unit, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

We examined the effects of electronic cigarette on platelet and vascular function after 4 months of use compared to tobacco smoking. Forty smokers without cardiovascular disease were randomized to smoke either conventional cigarettes or an electronic cigarette (nicotine concentration of 12 mg/ml). At baseline and after four months, we measured a) platelet function by Platelet Function Analyzer PFA-100 and Light Transmission Aggregometry, b) pulse wave velocity, c) plasma malondialdehyde levels as oxidative stress index and d) the exhaled CO level. After 4 months, continuation of conventional cigarette smoking further impaired platelet function compared to vaping as assessed by PFA (mean increase 27.1 vs 11.6 s, p for interaction = 0.048) and by LTA (decline 24.1 vs 9.4%, p for interaction = 0.045). Conversely, compared to smoking, vaping resulted in greater reduction of exhaled CO (6.9 ppm vs 2.6, p for interaction < 0.001), improvement of PWV (decrease of 0.8 m/s vs increase of 0.8 m/s, p for interaction = 0.020) and reduction of MDA (reduction 0.13 vs increase 0.19 nmol/L, p for interaction = 0.035). Switching to electronic cigarette for 4 months has a neutral effect on platelet function while it reduces arterial stiffness and oxidative stress compared to tobacco smoking.
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http://dx.doi.org/10.1016/j.fct.2020.111389DOI Listing
July 2020

Effects of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Endothelial Glycocalyx, Arterial Function, and Myocardial Work Index in Patients With Type 2 Diabetes Mellitus After 12-Month Treatment.

J Am Heart Assoc 2020 05 24;9(9):e015716. Epub 2020 Apr 24.

2nd Department of Internal Medicine Research Unit and Diabetes Centre Attikon Hospital Medical School National and Kapodistrian University of Athens Athens Greece.

Background We investigated the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and their combination on vascular and cardiac function of patients with type 2 diabetes mellitus. Methods and Results A total of 160 patients with type 2 diabetes mellitus were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40), or their combination (GLP-1RA+SGLT-2i) (n=40) as add-on to metformin. We measured at baseline and 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure, (c) global left ventricular longitudinal, circumferential, and radial strain, (d) myocardial work index (global work index) derived by pressure-myocardial strain loops using speckle tracking imaging. Twelve months posttreatment, all patients improved perfused boundary region, PWV, global longitudinal strain, global circumferential strain, and global radial strain (<0.05). GLP-1RA, SGLT-2i, and their combination showed a greater reduction of perfused boundary region, PWV, and central systolic blood pressure than insulin, despite a similar glycosylated hemoglobin reduction (<0.05). GLP-1RA or GLP-1RA+SGLT-2i provided a greater increase of global work index (12.7% and 17.4%) compared with insulin or SGLT-2i (3.1% and 2%). SGLT-2i or GLP-1RA and SGLT-2i showed a greater decrease of PWV (10.1% and 13%) and central and brachial systolic blood pressure than insulin or GLP-1RA (PWV, 3.6% and 8.6%) (<0.05 for all comparisons). The dual therapy showed the greatest effect on measured markers in patients with left ventricular ejection fraction <55% (<0.05). Conclusions Twelve-month treatment with GLP-1RA, SGLT-2i, and their combination showed a greater improvement of vascular markers and effective cardiac work than insulin treatment in type 2 diabetes mellitus. The combined therapy as second line was superior to either insulin or GLP-1RA and SGLT-2i separately. Registration URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT03878706.
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http://dx.doi.org/10.1161/JAHA.119.015716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428590PMC
May 2020

Cardiac imaging in cardiotoxicity: a focus on clinical practice.

Heart Fail Rev 2021 Sep;26(5):1175-1187

Mid-German Heart Center, Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120, Halle (Saale), Germany.

Cancer therapeutics induced cardiotoxicity has emerged as an important factor of long-term adverse cardiovascular outcomes in survivors of various malignant diseases. Early detection of myocardial injury in the setting of cancer treatment is important for the initiation of targeted cardioprotective therapy, in order to prevent irreversible cardiac dysfunction and heart failure, while not withholding a potentially life-saving cancer therapy. Cardiac imaging techniques including echocardiography, cardiac magnetic resonance, and nuclear cardiac imaging are the main tools for the identification of cardiotoxicity. There is also growing evidence for the detection of subclinical cardiac dysfunction in cancer patients by speckle tracking echocardiography. In this review article, we focus on current and emerging data regarding the role of cardiac imaging for the detection of changes in myocardial function related with cancer treatment in clinical practice.
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http://dx.doi.org/10.1007/s10741-020-09952-wDOI Listing
September 2021

β-Amyloid and mitochondrial-derived peptide-c are additive predictors of adverse outcome to high-on-treatment platelet reactivity in type 2 diabetics with revascularized coronary artery disease.

J Thromb Thrombolysis 2020 Apr;49(3):365-376

Laboratory of Haematology & Blood Bank Unit, 'Attikon University Hospital', School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Background And Aims: Increased β-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization.

Patients And Methods: In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) β-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up.

Results: Out of 121 patients, 32 showed HPR (LTAmax > 48%,). At baseline, HPR was associated with β-amyloid > 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, β-amyloid > 51 pg/ml and MOTS-c < 167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p < 0.05) after adjusting for confounders and medication. There was significant interaction between HPR and β-amyloid or MOTS-c for the prediction of MACE (p < 0.05). Patients with HPR and β-amyloid > 51 mg/dl or HPR and MOTS-c concentration < 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p < 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD.

Conclusions: Increased β-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712.
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http://dx.doi.org/10.1007/s11239-020-02060-4DOI Listing
April 2020

Late Takayasu Arteritis Diagnosis in a Female Patient With Prior Coronary Artery Bypass Grafting.

JACC Case Rep 2020 Jan 15;2(1):19-23. Epub 2020 Jan 15.

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

Takayasu arteritis is a rare cause of cardiovascular morbidity in the Western world. As consequence, vasculitis may be misdiagnosed and treated as atherosclerotic cardiovascular disease. We present a case of late Takayasu arteritis diagnosis, in a female patient with peripheral artery disease and previous coronary artery bypass grafting. ().
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http://dx.doi.org/10.1016/j.jaccas.2019.11.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301719PMC
January 2020

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

Impaired Arterial Elastic Properties and Endothelial Glycocalyx in Patients with Embolic Stroke of Undetermined Source.

Thromb Haemost 2019 Nov 17;119(11):1860-1868. Epub 2019 Aug 17.

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

Background And Purpose:  Cardioembolism is a postulated mechanism of embolic stroke of undetermined source (ESUS). We investigated endothelial glycocalyx, aortic elastic properties, oxidative stress, and their association with left atrial (LA) function in ESUS and healthy individuals.

Methods:  In 90 ESUS patients (age 50.4 ± 13.2) and 90 controls with similar risk factors, we measured: (1) perfused boundary region (PBR) of the sublingual arterial microvessels (range 5-25 µm), a marker inversely related with glycocalyx thickness, (2) pulse wave velocity (PWV), central systolic blood pressure (cSBP), and augmentation index (AIx), (3) LA volume and strain using speckle-tracking imaging, and (4) malondialdehyde (MDA) and protein carbonyls (PCs), as oxidative stress markers.

Results:  Compared with controls, ESUS had higher PWV, PBR, MDA, and PC levels as well as higher LA volume and reduced reservoir LA strain ( < 0.05). PBR > 1.2 μm of microvessel ranging from 5 to 9 μm and PWV > 10.2 m/s were associated with ESUS on multivariable analysis (odds ratio: 2.374 and 5.429,  < 0.05, respectively) and increased the c-statistic of the initial model from 0.54 to 0.71. In ESUS, glycocalyx damage (increased PBR) was related with increased PWV ( < 0.01) which was linked with LA reservoir strain after controlling for age, sex, and risk factors ( = 0.03). Increased MDA and PC were related with glycocalyx damage, increased PWV ( = 0.67 and  = 0.52), AIx, cSBP, and aortic atheroma ( < 0.01).

Conclusion:  Arterial function and endothelial glycocalyx are severely impaired in ESUS and are linked to LA dysfunction suggesting their contribution to ESUS pathogenesis.

Clinical Trial Registration:  URL-http://www.clinicaltrials.gov. Unique identifier: NCT03609437.
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http://dx.doi.org/10.1055/s-0039-1694752DOI Listing
November 2019

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 prognostic value of multiple electrode aggregometry and light transmittance aggregometry in stable cardiovascular patients with type 2 diabetes mellitus.

Thromb Res 2019 08 4;180:47-54. Epub 2019 Jun 4.

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

Aim: Limited data are available regarding the clinical relevance of platelet function measurements in stable patients with coronary artery disease (CAD). Our aim is to evaluate the agreement between multiple electrode aggregometry (MEA) and light transmittance aggregometry (LTA) in detecting clopidogrel low responders and their prognostic value in CAD patients with type 2 diabetes mellitus (T2DM) on dual platelet inhibition.

Methods: LTA and MEA were performed in 122 stable cardiovascular patients with T2DM. The upper quartile of patients according to maximum LTA (LTAmax) and MEA measurements were defined as clopidogrel low responders. Agreement between the two methods was evaluated by kappa statistics. We assessed the potential correlation between antiplatelet response and clinical outcome and the optimal cutoff value according to ROC analysis to predict the occurrence of major adverse cardiovascular events (MACE), during 1-year follow-up period.

Results: Cohen's kappa coefficients (0.214) indicated fair agreement (70.2%) between LTA and MEA. A total of 25 MACE occurred in 108 patients (23.1%). Patients with MACE had higher LTAmax than those without (57.1 ± 16.5 vs 49.3 ± 18.3, respectively, p = 0.023). MEA measurements were similar between patients with and without MACE (30.1 ± 15.4 vs 30.6 ± 20.8, respectively; p = 0.84). Multiple logistic regression showed LTAmax response as an independent predictor of death from cardiovascular causes (Odds Ratio, adjusted:0.2;0.05-0.81). ROC analysis indicated that LTAmax cutoff of 62.5% best predicted death (AUC = 0.67, sensitivity = 78%, specificity = 61.5%).

Conclusions: The assessment of platelet responsiveness remains highly test-specific. Our results support the prognostic role of LTA, but not MEA testing, for death risk evaluation in stable cardiovascular T2DM patients.
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http://dx.doi.org/10.1016/j.thromres.2019.06.001DOI Listing
August 2019

Laboratory Assessment of the Anticoagulant Activity of Apixaban in Patients With Nonvalvular Atrial Fibrillation.

Clin Appl Thromb Hemost 2018 Dec 1;24(9_suppl):194S-201S. Epub 2018 Oct 1.

Laboratory of Haematology & Blood Bank Unit, "Attiko" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Our aim is to determine the most appropriate laboratory tests, besides anti-factor Xa (anti-FXa) chromogenic assays, to estimate the degree of anticoagulation with apixaban and compare it with that of rivaroxaban in real-world patients. Twenty patients with nonvalvular atrial fibrillation treated with apixaban 5 mg twice daily and 20 patients on rivaroxaban 20 mg once daily were studied. Conventional coagulation tests, thrombin generation assay (TGA), and thromboelastometry (nonactivated TEM [NATEM] assay) were performed in the 40 patients and 20 controls. The anti-FXa chromogenic assays were used to measure apixaban and rivaroxaban plasma levels. The NATEM measurements showed no significant difference between the 2 groups of patients. Concerning TGA, endogenous thrombin potential (ETP) was significantly decreased in patients on rivaroxaban as compared to those treated with apixaban ( < .003). A statistically significant, strong inverse correlation between apixaban plasma concentrations and ETP ( < .001) was observed. Apixaban significantly reduces ETP compared to controls, but to a lesser extent than rivaroxaban. Thrombin generation assay might provide additional information on apixaban exposure, which is required in order to individualize treatment especially for patients with a high bleeding risk. Our findings have to be further investigated in studies with larger sample sizes, in the entire range of apixaban exposure, with other direct oral anticoagulants, and in relation to clinical outcomes.
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http://dx.doi.org/10.1177/1076029618802364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714834PMC
December 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

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

The time difference between clinical improvement and exercise tolerance increase following pulmonary thromboendarterectomy.

Int J Cardiol 2016 Nov 30;222:267-269. Epub 2016 Jul 30.

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

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http://dx.doi.org/10.1016/j.ijcard.2016.07.244DOI Listing
November 2016

Comparative Assessment of the Anticoagulant Activity of Rivaroxaban and Dabigatran in Patients With Nonvalvular Atrial Fibrillation: A Noninterventional Study.

Medicine (Baltimore) 2016 Apr;95(14):e3037

From the Laboratory of Haematology and Blood Bank Unit, "Attiko" Hospital(AET, EK, PD); Second Cardiology Department, "Attiko" Hospital(II, KK, IP, JL); Second Department of Critical Care Medicine, "Attiko" Hospital(PK, IT); Department of Microbiology (VK), School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; and Humanitas Clinical and Research Center (SB), Rozzano, Milan, Italy.

There is a shortage of data in everyday clinical practice about the anticoagulant effects caused by the new oral anticoagulants (NOAs). Our aim was to estimate the intensity of anticoagulant activity induced by rivaroxaban 20 mg qd and dabigatran 110 mg bid among patients with nonvalvular atrial fibrillation (NV-AF).We studied 20 patients with NV-AF treated with dabigatran, and 20 patients treated with rivaroxaban. We performed conventional coagulation tests, thrombin generation (TG) test, thromboelastometry (ROTEM), and epinephrine-induced light transmission aggregometry (LTA) in all 40 patients and 20 controls. Hemoclot Thrombin Inhibitors (HTI) and Factor Xa Direct Inhibitor (DiXaI) assay were used to measure dabigatran and rivaroxaban plasma levels, respectively.Measurements of all assays estimating anticoagulant activity across the 2 patient groups were similar, except for aPTT. Patients on dabigatran exhibited statistically significantly prolonged aPTT values (P < 0.001). In LTA, patients on dabigatran also showed decreased aggregation compared to those on rivaroxaban (P = 0.045). Regarding the TG test, there was no association between endogenous thrombin potential (ETP) and rivaroxaban plasma levels (P = 0.33) as opposed to dabigatran levels (P < 0.001), but significant correlations were observed between rivaroxaban plasma concentrations and kinetic parameters of TG assay (Tlag, P = 0.045; Tmax, P = 0.016; and Cmax, P = 0.003).Based on ROTEM and TG assays, the anticoagulant effects induced by the 2 drugs given in the specific dose regimens in real-world patients were comparable. Only platelet aggregation was found to be more affected by dabigatran as compared to rivaroxaban.
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http://dx.doi.org/10.1097/MD.0000000000003037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998746PMC
April 2016
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