Coronary Artery Disease: Nihoyannopoulos P

Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, Voigt JU, Zamorano JL, Anonymous00198. · Institute of Clinical Physiology, Via G. Moruzzi, 1, 56124 Pisa, Italy. · Eur J Echocardiogr. · Pubmed #18579481 links to  free full text

Abstract: Stress echocardiography is the combination of 2D echocardiography with a physical, pharmacological or electrical stress. The diagnostic end point for the detection of myocardial ischemia is the induction of a transient worsening in regional function during stress. Stress echocardiography provides similar diagnostic and prognostic accuracy as radionuclide stress perfusion imaging, but at a substantially lower cost, without environmental impact, and with no biohazards for the patient and the physician. Among different stresses of comparable diagnostic and prognostic accuracy, semisupine exercise is the most used, dobutamine the best test for viability, and dipyridamole the safest and simplest pharmacological stress and the most suitable for combined wall motion coronary flow reserve assessment. The additional clinical benefit of myocardial perfusion contrast echocardiography and myocardial velocity imaging has been inconsistent to date, whereas the potential of adding - coronary flow reserve evaluation of left anterior descending coronary artery by transthoracic Doppler echocardiography adds another potentially important dimension to stress echocardiography. New emerging fields of application taking advantage from the versatility of the technique are Doppler stress echo in valvular heart disease and in dilated cardiomyopathy. In spite of its dependence upon operator's training, stress echocardiography is today the best (most cost-effective and risk-effective) possible imaging choice to achieve the still elusive target of sustainable cardiac imaging in the field of noninvasive diagnosis of coronary artery disease.

Becher H, Chambers J, Fox K, Jones R, Leech GJ, Masani N, Monaghan M, More R, Nihoyannopoulos P, Rimington H, Senior R, Warton G, Anonymous00150. · British Society of Echocardiography, c/o British Cardiac Society, 9 Fitzroy Square, London W1T 5HW, UK. · Heart. · Pubmed #15564422 links to  free full text

This publication has no abstract.

Rakhit DJ, Becher H, Monaghan M, Nihoyannopoulos P, Nihoyannopoulis P, Senior R. · Department of Cardiology, Northwick Park Hospital, Watford Road, Harrow, UK. · Eur J Echocardiogr. · Pubmed #17459779 links to  free full text

Abstract: Recent updates in the field of echocardiography have resulted in improvements in both image quality and techniques allowing echocardiography to maintain it's position as the primary non-invasive imaging modality. In particular, the development of new ultrasound contrast agents and imaging techniques have now made possible the assessment of myocardial perfusion. Myocardial contrast echocardiography utilises acoustically active gas filled microspheres (microbubbles), which have rheology similar to that of red blood cells. The detection of myocardial perfusion during echocardiographic examinations permits simultaneous assessment of global and regional myocardial structure, function, and perfusion, enabling the optimal non-invasive assessment of coronary artery disease. Myocardial contrast echocardiography is equally adept in assessing chronic coronary artery disease, acute coronary syndromes and hibernating myocardium.

Senior R, Monaghan M, Becher H, Mayet J, Nihoyannopoulos P, Anonymous00133. · Department of Cardiovascular Medicine, Northwick Park Hospital, Harrow HA1 3UJ UK, UK. · Heart. · Pubmed #15772187 links to  free full text

Abstract: Stress echocardiography today has matured into a robust and reliable technique not only for the diagnosis of suspected coronary artery disease (CAD) but also for the accurate risk stratification of patients with suspected and established CAD. This is mainly because of rapid advances in image acquisition, digital display, and the development of harmonic and contrast imaging. Stress echocardiography today is also utilised in patients with heart failure both for assessing the cause of heart failure and determining the extent of hibernating myocardium. With advances in myocardial perfusion imaging, stress echocardiography now allows simultaneous assessment of myocardial function and perfusion. Tissue Doppler imaging allows quantitation of wall motion. Ready availability and reliability makes stress echocardiography a cost effective technique for the assessment of CAD.

Ikonomidis I, Athanassopoulos G, Lekakis J, Venetsanou K, Marinou M, Stamatelopoulos K, Cokkinos DV, Nihoyannopoulos P. · Department of Clinical Therapeutics, University of Athens, Alexandra Hospital, Athens, Greece. · Circulation. · Pubmed #16286589 links to  free full text

Abstract: BACKGROUND: Interleukin-6 (IL-6) and macrophage colony stimulating factor plasma levels are elevated in acute coronary syndromes. IL-6 has an inherent negative inotropic action and, with tissue factor (TF), mediates the ischemia-reperfusion myocardial injury. We hypothesized that inducible ischemia leads to cytokine production, TF expression, and consequently persistent left ventricular dysfunction after dobutamine stress echocardiography (DSE) in coronary artery disease patients. METHODS AND RESULTS: DSE was performed in 103 patients with angiographically documented coronary artery disease. Blood samples were obtained at rest, at peak stress, and 30 minutes after cessation of dobutamine infusion for measurement of macrophage colony stimulating factor, IL-6, and TF. New or worsening wall motion abnormalities at peak stress and their duration into recovery were noted. Median IL-6 and TF levels were increased at peak stress and at 30 minutes into recovery compared with rest (2.7 and 2.4 versus 2.1 pg/mL for IL-6, 310 and 385 versus 266 pg/mL for TF [P<0.01] in patients with an ischemic response; n=55). Compared with rest, a greater release of IL-6 at peak stress and recovery was observed in patients with increasing number of ischemic segments at peak DSE (2 versus 3 to 4 versus 5 to 6 versus 7 to 8 segments; P=0.03). The time to recovery of wall motion abnormalities was also associated with IL-6 levels at peak stress and recovery (r=0.51 and r=0.39, P<0.05). Macrophage colony stimulating factor levels remained unchanged throughout DSE. CONCLUSIONS: Reversible ischemia induced during DSE increases IL-6 and TF plasma levels. IL-6 is related to the extent of left ventricular dysfunction at peak stress and to persistent LV dysfunction during recovery.

Brown AS, Calachanis M, Evdoridis C, Hancock J, Wild S, Prasan A, Nihoyannopoulos P, Monaghan MJ. · Department of Cardiology, Beaumont Hospital, Dublin, Ireland. · Ir J Med Sci. · Pubmed #15732229 No free full text.

Abstract: BACKGROUND: Stress echocardiography is useful for assessing patients with coronary artery disease unable to undergo formal exercise testing. Considerable skill is required to avoid large intra- and inter-observer variability due to poor endocardial definition. Intravenous ultrasound contrast agents are now available which may improve this variability. AIM: To study intravenous Sonovue in assessing wall motion score and ejection fraction (EF) during stress echocardiography. METHODS: Thirty-eight patients undergoing arbutamine stress echocardiography for known or suspected coronary artery disease were studied. Echocardiographic analysis of wall motion score index, endocardial border detection (EBD) and EF was performed at rest and at peak stress before and after intravenous injection of Sonovue, by experienced and inexperienced observers. RESULTS: All three observers noted an improvement in endocardial border definition following Sonovue (p=<0.001). At baseline, there was a significant difference in wall motion score index between experienced and inexperienced observers at rest (p=0.01) and at peak stress (p=0.001). Following Sonovue administration this was no longer significant (p=0.07, p=0.114). Intra-observer variability of end diastolic, end systolic volumes (ESV) and EF improved following contrast (p<0.05) at rest and during stress. CONCLUSION: Sonovue significantly improved EBD and reduced intra-observer variability of EF at rest and during peak arbutamine infusion.

Ikonomidis I, Andreotti F, Nihoyannopoulos P. · University of Athens, Department of Clinical Therapeutics, Alexandra Hospital, Athens, Greece. · Heart. · Pubmed #15020512 links to  free full text

Abstract: OBJECTIVES: To evaluate whether aspirin reduces the incidence and frequency of daily life myocardial ischaemia in a cohort of patients with chronic stable coronary artery disease. SETTING: Tertiary referral centre. METHODS: 60 patients with chronic stable coronary artery disease underwent 48 hour Holter monitoring to assess the incidence and frequency of daily life myocardial ischaemia. Those with myocardial ischaemia (40/60) entered a double blind, crossover trial of aspirin (300 mg/day for three weeks) versus placebo. After each treatment arm, 48 hour Holter monitoring was repeated and urinary thromboxane (Tx) B2, 11-dehydro-TxB2, plasma prothrombin fragment F1+2, macrophage colony stimulating factor (MCSF), and interleukin (IL)-6 were measured. RESULTS: Aspirin reduced the total number and duration of ischaemic episodes from 339 to 251 and from 1765 to 1365 minutes, respectively (p < 0.01 for both). TxB2 was also reduced from 0.2 to 0.1 ng/mg creatinine, 11-dehydro-TxB2 from 3.3 to 1.3 ng/mg creatinine, F1+2 from 1.5 to 1.2 nmol/l, MCSF from 991 to 843 pg/ml, and IL-6 from 3.5 to 2.9 pg/ml (p < 0.05 for all). 11-dehydro-TxB2 excretion with and without aspirin was related to MCSF concentrations (p < 0.01), and the percentage reduction of MCSF by aspirin was related to the reduction of 11-dehydro-TxB2 (p < 0.05) and the reduction of the ischaemic burden compared with placebo (p < 0.05). CONCLUSIONS: In patients with daily life ischaemia, aspirin reduces the incidence and frequency of ischaemic episodes as well as the systemic concentrations of haemostatic/inflammatory markers. Aspirin may prevent transient coronary flow reductions through platelet, thrombin, and cytokine inhibition.

Barnes E, Baker CS, Dutka DP, Rimoldi O, Rinaldi CA, Nihoyannopoulos P, Camici PG, Hall RJ. · Department of Cardiology, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, UK. · Heart. · Pubmed #10677406 links to  free full text

Abstract: OBJECTIVE: To determine whether pharmacological stress leads to prolonged but reversible left ventricular dysfunction in patients with coronary artery disease, similar to that seen after exercise. DESIGN: A randomised crossover study of recovery time of systolic and diastolic left ventricular function after exercise and dobutamine induced ischaemia. SUBJECTS: 10 patients with stable angina, angiographically proven coronary artery disease, and normal left ventricular function. INTERVENTIONS: Treadmill exercise and dobutamine stress were performed on different days. Quantitative assessment of systolic and diastolic left ventricular function was performed using transthoracic echocardiography at baseline and at regular intervals after each test. RESULTS: Both forms of stress led to prolonged but reversible systolic and diastolic dysfunction. There was no difference in the maximum double product (p = 0.53) or ST depression (p = 0.63) with either form of stress. After exercise, ejection fraction was reduced at 15 and 30 minutes compared with baseline (mean (SEM), -5.6 (1.5)%, p < 0.05; and -6.1 (2.2)%, p < 0. 01), and at 30 and 45 minutes after dobutamine (-10.8 (1.8)% and -5. 5 (1.8)%, both p < 0.01). Regional analysis showed a reduction in the worst affected segment 15 and 30 minutes after exercise (-27.9 (7.2)% and -28.6 (5.7)%, both p < 0.01), and at 30 minutes after dobutamine (-32 (5.3)%, p < 0.01). The isovolumic relaxation period was prolonged 45 minutes after each form of stress (p < 0.05). CONCLUSIONS: In patients with coronary artery disease, dobutamine induced ischaemia results in prolonged reversible left ventricular dysfunction, presumed to be myocardial stunning, similar to that seen after exercise. Dobutamine induced ischaemia could therefore be used to study the pathophysiology of this phenomenon further in patients with coronary artery disease.

Ikonomidis I, Athanassopoulos G, Stamatelopoulos K, Lekakis J, Revela I, Venetsanou K, Marinou M, Monaco C, Cokkinos DV, Nihoyannopoulos P. · 2nd Cardiology Department, Attikon Hospital, University of Athens, Athens, Greece. · Am Heart J. · Pubmed #18657656 No free full text.

Abstract: BACKGROUND: Interleukin-6 (IL-6) and tissue factor (TF) are elevated after myocardial ischemia during dobutamine stress echo (DSE). We examined the incremental prognostic value of IL-6 or TF measured during DSE over echocardiographic and clinical factors in patients with chronic coronary artery disease (CAD). METHODS: We studied 106 patients with angiographically documented CAD. IL-6 and TF were measured at rest, peak, and during recovery. A wall motion score index was calculated. RESULTS: Fifty-seven (54%) patients had ischemia at DSE. During follow-up (63.7 +/- 20 months), 36 patients (33%) had an adverse event (12 cardiac deaths, 24 acute coronary events). Patients with events had a higher peak IL-6 (P = .02) but similar rest and recovery IL-6 than those without. Patients with peak IL-6 > or =3.14 pg/mL (upper tertile) had a hazard ratio of 2.7 (95% CI 1.44-5.37) (P < .01 for an adverse event). The addition of peak wall motion score index in a multivariable model including risk factors, ejection fraction, revascularization, and multivessel disease increased the model's c statistic from 0.66 to 0.70 (P = .04). The addition of peak IL-6 further increased the model's c statistic to 0.75 (P = .04). Tissue factor was not related with cardiac events. CONCLUSIONS: Interleuikin-6 levels measured during the peak phase of DSE incrementally contribute to risk stratification in patients with chronic CAD.

Ikonomidis I, Lekakis J, Vamvakou G, Loizou S, Revela I, Andreotti F, Kremastinos DT, Nihoyannopoulos P. · 2nd Cardiology Department, Attikon Hospital, University of Athens, Perikleous 19, N. Chalkidona, Athens, 14343, Greece. · Heart. · Pubmed #17934000 No free full text.

Abstract: BACKGROUND: Circulating anticardiolipin antibodies (aCL) may cause endothelial dysfunction. We investigated whether aCL are related to platelet activation, thrombin generation and daily-life ischaemia in patients with chronic coronary artery disease (CAD). METHODS: We measured (medians 25th-75th percentile) IgG, IgM, IgA aCL serum levels (Arbitrary Elisa Units, AEU), prothrombin fragments (F1+2, nmol/l), 24 h urine excretion of 11-dehydrothromboxane B2 (11-DHTXB2, ng/mg creatinine) creatine kinase (CK) and its cardiac isoenzyme CK-MB (IU/l) in 60 patients with angiographically documented CAD and in 40 age and sex matched controls. Patients underwent a 48 h Holter monitoring for assessment of the number and duration of ischaemic episodes. RESULTS: Patients had higher IgA-aCL levels than controls (3.2 vs 2.4 AEU, p = 0.002). Increased IgA-ACA levels were related to increased number and duration of ischaemic episodes (p<0.01). By ANOVA, patients with >or=10 ischaemic episodes (3rd tertile) or duration of ischaemia >or=32min (3rd tertile) had higher IgA-aCL than those with lower ischaemic burden (4.95 vs 3 vs 2.5 AEU, p = 0.002 and 4.9 vs 3 vs 2.5 AEU, p = 0.001 respectively). Patients with >or=2 ischaemic episodes (2nd and 3rd tertile) had higher 11-DHTXB2, than those with minimal ischaemia (2< episodes, 1st tertile) (p = 0.001). CK and CK-MB were within normal range after Holter monitoring. Receiver operating curve analysis showed a greater area under the curve for IgA-aCL than for 11-DHTXB2 in predicting severe ischaemia (>or=10 ischemic episodes or >or=32 min duration of ischaemia). CONCLUSION: Increasing IgA-aCL levels are associated with increasing ischemic burden in patients with CAD.

Ikonomidis I, Lekakis J, Vamvakou G, Loizou S, Revela I, Andreotti F, Kremastinos DT, Nihoyannopoulos P. · Second Cardiology Department, Attikon University Hospital, University of Athens, N Chalkidona, Athens, Greece. · Eur J Clin Invest. · Pubmed #17087777 No free full text.

Abstract: BACKGROUND: Anticardiolipin antibodies (aCL) have been found to be elevated in patients with coronary artery disease (CAD) and have been associated with an adverse outcome owing to their prothrombotic activity. The aim of this study was to investigate the effect of aspirin treatment on aCL levels in patients with chronic CAD. MATERIALS AND METHODS: Forty patients with chronic CAD scheduled for elective coronary artery bypass graft surgery (CABG) and 40 healthy controls participated in the study. Patients were treated with 300 mg of aspirin once daily (o.d.) for the first 12 days and placebo for the following 12 days before CABG in a double-blind, cross-over trial. Immunoglobulin (Ig) G-, IgM-, IgA-aCL and C-reactive protein (CRP) levels were measured in the controls and at the end of each treatment period in the patients with CAD. RESULTS: The IgA- and IgG-aCL levels were greater in patients with CAD than in the controls. Compared with the placebo, IgA, IgG subtypes and CRP levels were reduced after aspirin treatment (P = 0.001, P = 0.02, P = 0.04, respectively). The percentage reduction of IgA- and IgG-aCL was related to the percentage reduction of CRP after aspirin (P < 0.05). CONCLUSION: Aspirin treatment with 300 mg o.d. reduced the serum levels of IgA and IgG subtypes in patients with chronic CAD in parallel to a reduction in CRP. These findings offer an additional pathophysiological mechanism of the beneficial effects of aspirin in patients with chronic CAD.

Ikonomidis I, Lekakis J, Vamvakou G, Andreotti F, Nihoyannopoulos P. · Imperial College School of Medicine, National Heart and Lung Institute, Cardiology Department, Hammersmith Hospital, London, United Kingdom. · Am Heart J. · Pubmed #15894964 No free full text.

Abstract: BACKGROUND: Smoking is associated with endothelial dysfunction. Cytokines released by injured endothelium promote vascular interactions with leukocytes and platelets. We investigated whether (a) cigarette smoking is linked to increased cytokine production, which may mediate platelet activation and thrombin generation in chronic coronary artery disease (CAD), and (b) aspirin treatment inhibits smoking-related changes on cytokines, platelets, and thrombin. METHODS AND RESULTS: Plasma macrophage-colony-stimulating factor (M-CSF) and C-reactive protein (CRP) were measured in 100 patients with chronic CAD, 60 of whom were chronic smokers. Prothrombin fragments 1+2 and urinary 11-dehydro-thromboxane B2 (TXB2) were additionally measured in 60 of 100 patients (30 of whom were smokers) and in 24 healthy controls. Smokers (n = 20) matched for age, myocardial ischemia, and other risk factors with 20 nonsmokers entered a double-blind crossover trial of aspirin (300 mg/d for 3 weeks) versus placebo. Blood and urine measurements were repeated after each treatment. Compared with nonsmokers, smokers had 3-fold median M-CSF (1499 vs 476 pg/mL), 2-fold CRP (1.5 vs 0.8 mg/L), and higher 11-dehydro-TXB 2 (3.6 vs 2.1 ng/mg creatinine, P < .01 for all comparisons). After aspirin treatment, M-CSF, CRP, 11-dehydro-TXB 2 , and prothrombin fragments 1+2 remained higher in smokers compared with nonsmokers despite a significant reduction of these markers by aspirin (P < .05). M-CSF remained related to 11-dehydro-TXB 2 excretion during both treatment phases (P < .01) suggesting that cytokine-mediated thromboxane A 2 production was not altered by aspirin. CONCLUSIONS: Smoking is associated with increased M-CSF, CRP, and platelet activity. Although aspirin treatment reduces the proinflammatory and procoagulant markers in smokers, it does not abolish the proinflammatory effects of smoking in patients with chronic CAD.

Ikonomidis I, Lekakis J, Revela I, Andreotti F, Nihoyannopoulos P. · Department of Clinical Therapeutics, University of Athens, Alexandra Hospital, Vas. Sofias 80, Athens 11528, Greece. · Eur Heart J. · Pubmed #15800017 links to  free full text

Abstract: AIMS: We investigated, in a 6 year follow-up study, whether circulating levels of C-reactive protein (CRP) and macrophage colony stimulating factor (MCSF) have an independent or complementary prognostic value in patients with chronic coronary artery disease (CAD). METHODS AND RESULTS: MCSF and CRP were measured in 100 patients with chronic CAD. Of 95 (33%) patients, 31 who completed the 6 year follow-up presented adverse events (death, myocardial infarction, and unstable angina). In multivariable analysis (including traditional risk factors and medications), the upper tertiles of MCSF (> or =814 pg/mL) and CRP (> or =2.5 mg/L) levels were independently associated with a 13- and 6-fold increase in risk of events, respectively (P<0.01). Patients with combined high CRP and MCSF had a higher absolute risk of events than patients with elevated MCSF or CRP alone (75 vs. 59 vs. 32%, respectively, P<0.01). The mean event-free time was 39, 64, and 52 months in patients with elevated MCSF, elevated CRP, and their combination, respectively. CONCLUSION: In patients with chronic CAD, the prognostic value of MCSF is independent and complementary to that of CRP. MCSF is a particularly useful prognostic marker when CRP levels are low, but also provides additional information concerning risk and time-course of events in patients with elevated CRP.

Parthenakis FI, Kochiadakis GE, Skalidis EI, Kanakaraki MK, Mezilis NE, Kanoupakis EM, Vardas PE, Nihoyannopoulos P. · Cardiology Department, University Hospital of Heraklion, Crete, Greece. · Clin Cardiol. · Pubmed #11061051 No free full text.

Abstract: BACKGROUND: The presence of atherosclerotic lesions in the thoracic aorta by transesophageal echocardiography (TEE) appears to be a marker for the presence of significant coronary artery disease (CAD) in the general population. HYPOTHESIS: We investigated whether atherosclerotic lesions in the thoracic aorta, by multiplane TEE, could be a marker for CAD in elderly patients. METHODS: In all, 127 patients (67 men, 60 women, aged 68 +/- 13 years), underwent a TEE study with imaging of the thoracic aorta and cardiac catheterization with coronary angiography. The presence of a distinct, linear, or focal, highly echogenic mass protruding into the vessel lumen was the criterion for the diagnosis of atherosclerotic plaque. RESULTS: Atherosclerotic lesions were found in 30 of 36 patients (83.3%) with and in 20 of 91 (22%) without CAD. Of the 41 patients > or = 70 years, atherosclerotic lesions were detected in 14 of 17 (82.3%) with and in 13 of 24 patients (54%) without CAD. The sensitivity, specificity, and positive and negative predictive values in this group were 82.3, 46, 52, and 78.6%, respectively. Multivariate logistic regression analysis revealed that in patients aged > or = 70 years only advanced atherosclerotic lesions were independent predictors of significant CAD. However, the high negative predictive value of the method indicates that the absence of aortic plaque is a strong predictor of the absence of CAD. CONCLUSIONS: The presence of atherosclerotic lesions in the thoracic aorta is a strong predictor of CAD only in patients < 70 years old. However, the negative predictive value of the method is high for all patients regardless of age.

Tousoulis D, Rallidis L, Cokkinos P, Davies G, Nihoyannopoulos P. · Cardiology Unit, National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom. · Am Heart J. · Pubmed #10539818 No free full text.

Abstract: BACKGROUND: Quantitative coronary angiography has been shown to allow accurate assessment of coronary stenosis. Exercise and dobutamine stress echocardiography both are established methods for assessing the functional importance of coronary stenosis. The relation, however, between exercise and dobutamine stress-induced wall motion abnormalities and the severity and location of stenosis remains controversial. METHODS AND RESULTS: Thirty patients with single-vessel coronary artery disease with >/=50% minimal luminal reduction and stable angina participated in the study. Severity of coronary artery stenosis was assessed by means of computed angiography. During peak exercise echocardiography 23 patients had wall motion abnormalities and 7 did not. A positive test result was associated with severity of stenosis >/=80% for 65% of stenoses (P <.05 versus severity of stenosis <80%) and with a proximal location of 94% of stenoses (P <.01 versus middle and distal stenoses). A significant correlation was found between area of stenosis and difference in wall motion score between rest and peak exercise (r = 0.53, P <.01). The proportion of positive exercise stress was greater among stenoses with severity <80% (62% versus 46% dobutamine stress, P <.05). During dobutamine stress echocardiography 18 patients had wall motion abnormalities and 12 patients did not. A positive test result was associated with severity of stenosis >/=80% in 72% of stenoses (P <.05 versus severity of stenosis <80%) and with a proximal location in 81% of stenoses (P <.01 versus middle and distal stenoses). A weak correlation was found between area of stenosis and difference in wall motion score between rest and peak dobutamine stress (r = 0.37, P <.05). CONCLUSIONS: Among patients with single-vessel coronary artery disease, positive stress echocardiographic test results usually are associated with proximal >/=80% stenosis. Patients with <80% stenoses are more likely to have a positive exercise stress test result than a positive dobutamine stress test result.