Kostas Toutouzas

Expert review document part 2: methodology, terminology and clinical applications of optical coherence tomography for the assessment of interventional procedures.

This document is complementary to an Expert Review Document on Optical Coherence Tomography (OCT) for the study of coronary arteries and atherosclerosis.1 The goal of this companion manuscript is to provide a practical guide framework for the appropriate use and reporting of the novel frequency domain (FD) OCT imaging to guide interventional procedures, with a particular interest on the comparison with intravascular ultrasound (IVUS).1–4 In the OCT Expert Review Document on Atherosclerosis, a comprehensive description of the physical principles for OCT imaging and time domain (TD) catheters (St Jude Medical, Westford, MA, USA) was provided.1 The main advantage of FD-OCT is that the technology enables rapid imaging of the coronary artery, using a non-occlusive acquisition modality. The FD-OCT catheter (DragonflyTM; St Jude Medical) employs a single-mode optical fibre, enclosed in a hollow metal torque wire that rotates at a speed of 100 r.p.s. It is compatible with a conventional 0.014″ angioplasty guide wire, inserted into a short monorail lumen at the tip. The frequency domain optical coherence tomography lateral resolution is improved in comparison with TD-OCT, while the axial resolution did not change. These features, together with reduced motion artefacts and an increased maximum field of view up to 11 mm, have significantly improved both the quality and ease of use of OCT in the catheterization laboratory.3,4 However, the imaging depth of the FD-OCT is still limited to 0.5–2.0 mm.5 The main obstacle to the adoption of TD-OCT imaging in clinical practice is that OCT cannot image through a blood field, and therefore requires clearing or flushing of blood from the lumen.1 The 6 Fr compatible DragonflyTM FD-OCT catheter is so far the only one in the market, as two other systems from Volcano and Terumo, which …

Oxidative stress and endothelial function: therapeutic interventions.

Cardiovascular risk factors, such as hypertension, hypercholesterolemia, diabetes mellitus, or chronic smoking, stimulate the production of reactive oxygen species (ROS) in the vascular wall. Oxidative stress and endothelial dysfunction in the coronary and peripheral circulation have important prognostic implications for subsequent cardiovascular events. The pathophysiologic causes of oxidative stress are likely to involve changes in a number of different enzyme systems. Reactive oxygen species (ROS) are produced by various oxidase enzymes, including nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, uncoupled endothelial NO synthase (eNOS), cyclooxygenase, glucose oxidase, and lipooxygenase, and mitochondrial electron transport. Decreased NO production due to changes in the expression and activity of eNOS and increased degradation of NO, by reaction with superoxide account for the reduction in endothelium-dependent vascular relaxation. Recently, a variety of antioxidants have been extensively studied in clinical trials for the prevention and treatment of atherosclerosis. In small clinical studies both vitamins C and E may improve endothelial function in high-risk patients. However, larger interventional trials have been controversial, suggesting potential harm in certain high-risk populations. Antihypertensive and hypolipidemic medications exhibit well-documented antioxidant effects and improve endothelial function. However, the discussion of recent patents with the novel antioxidant strategies are required to clarify the role of antioxidant intervention in vascular diseases.

Selective Serotonin Reuptake Inhibitors Modify the Effect of β-Blockers on Long-Term Survival of Patients With End-Stage Heart Failure and Major Depression

BACKGROUND Major depression (MD) is a key feature in heart failure (HF), and it is unclear whether common antidepressive medications interact with cardiovascular drugs used for the treatment of patients with MD and HF, affecting their efficacy. We examined the impact of MD on long-term survival of patients with end-stage severe HF. We also evaluated the interaction between antidepressive medication and beta-blockers on the clinical outcome of these patients. METHODS AND RESULTS The study population consisted of 250 patients with end-stage severe HF. Sixty-one percent of these patients suffered MD and were receiving selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCA). All patients were followed prospectively for 18 months. The primary end point was cardiovascular death. At baseline, patients with severe MD had higher serum interleukin 6 (P < .05) and soluble vascular cell adhesion molecule (P < .01). During the follow-up, 167 cardiovascular deaths were reported, and MD was 1 of the major predictors of cardiovascular death (P = .031), whereas treatment with angiotensin receptor inhibitors and statins were also important negative predictors of mortality (P = .036 and P = .039, respectively). Although beta-blockers had a borderline nonsignificant effect on cardiovascular mortality in the overall population, they had a striking beneficial effect among those patients with major depression receiving SSRIs (P = .006), whereas they had a negative effect on mortality in those patients receiving SNRIs/TCAs (P = .025). CONCLUSIONS MD is an independent predictor of cardiovascular death in patients with end-stage HF. beta-blockers are associated with lower cardiovascular mortality in patients with end-stage HF and depression only when they are combined with SSRIs.

Relationships of CRP and P Wave Dispersion With Atrial Fibrillation in Hypertensive Subjects

BACKGROUND Although inflammation has been shown to be implicated in the pathophysiology of atrial fibrillation (AF), little is known about its involvement in the accompanying atrial electrical remodeling expressed by P wave dispersion (P(disp)). METHODS Fifty hypertensive subjects with documented paroxysmal AF (AF group) and 50 matched for body mass index, sex and office systolic blood pressure (BP) subjects with no history of AF (SR group) were subjected to electrocardiogram (ECG) and P(disp) assessment, hs-CRP determination, a complete echocardiographic study and 24-h ambulatory BP monitoring. RESULTS The AF as compared to the SR subjects were older by 14 years (P < 0.0001) and they exhibited lower office and 24-h diastolic BP (7 mm Hg, P < 0.0001 and by 8 mm Hg, P < 0.0001, respectively) and higher office and 24-h pulse pressure (by 4 mm Hg, P = 0.03 and 6 mm Hg, P = 0.001, respectively) mean values. A higher mean of left atrial (LA) diameter index (by 1.9 mm/m(2), P < 0.0001) and left ventricular mass index (by 16 g/m(2), P < 0.0001) were observed in the AF vs. SR group. P(disp) mean and hs-CRP median values were higher in the AF group (by 22 ms, P < 0.0005 and by 4.63 mg/l, P < 0.0005, respectively). Standard multiple and multiple logistic regression analysis identified log(10)(hs-CRP) as independent determinant of P(disp) and log(10)(CRP) and P(disp) as independent determinants of AF. CONCLUSIONS In hypertensive subjects hs-CRP and P(disp) are interrelated and associated with AF, suggesting an active implication of inflammation in the atrial electrophysiological remodeling predisposing to AF.

Impact of waist circumference on cardiac phenotype in hypertensives according to gender.

Our aim was to assess the differential effect of waist circumference on left‐ventricular (LV) structural and functional alterations, in hypertensive males and females. One thousand seven hundred and eighty nine consecutive, nondiabetic, essential hypertensives (aged 55.8 ± 13.5 years, 966 females), included in the 3H Study, an ongoing registry of hypertension‐related‐target‐organ damage, were classified to obese and nonobese groups according to Adult Treatment Panel III criteria. All participants underwent complete echocardiographic study including LV diastolic function evaluation by means of conventional and tissue Doppler imaging (TDI) methods, averaging early and late diastolic mitral annular peak velocities (Em, Am, Em/Am) from four separate sites of measurement. Hypertensive obese women compared with nonobese exhibited significantly greater LV mass index and prevalence of LV hypertrophy (by 5.5 g/m2, P = 0.003, and 8.8%, P = 0.005, respectively), while such differences were not present among men. Obese women compared to nonobese ones were accompanied by lower transmitral E/A (by 0.08, P < 0.001), TDI‐derived Em/Am (by 0.12, P < 0.001), and higher E/Em ratio (by 0.8, P = 0.016). In contrast, hypertensive obese men compared to nonobese ones exhibited lower E and Em (by 0.04 m/s and 0.6 cm/s, both P < 0.05). A significant interaction between sex and abdominal obesity was observed only regarding TDI‐derived Am and Em/Am. Furthermore, waist circumference was a predictor of E/A (β = −0.097, P = 0.002) and Em/Am (β = −0.116, P = 0.001), independently of body size, in females but not in males. The adverse effect of abdominal obesity on LV alterations is more pronounced among female hypertensives, suggesting that routine measurement of waist circumference provides additional information on cardiac phenotype especially in women.

The implementation of a national trauma registry in Greece. Methodology and preliminary results.

BACKGROUND Trauma is a leading cause of death worldwide and a major health problem of the modern society. Trauma systems are considered the gold standard of managing patients with trauma. An integral part of any trauma system is a trauma registry. In Europe, and particularly in Greece, trauma registries and systems are in an embryonic stage. In this study, we present an attempt to record trauma in Greece. METHODS The Hellenic Society of Trauma and Emergency Surgery invited all the official representatives of the society throughout the country to participate in the study. In succeeding meetings of the representatives, the reporting form was developed and the inclusion criteria were defined meticulously. Inclusion criteria were defined as patients with trauma requiring admission, transfer to a higher level center, or arrived dead or died in the emergency department of the reporting hospital. All reports were accumulated by the Hellenic Trauma society, imported in an electronic database, and analyzed. RESULTS Thirty-two hospitals receiving patients with trauma participated in the country, representing 40% of the countrys healthcare facilities and serving 40% of the countrys population. In 12 months time, (October 2005 to September 2006), 8,862 patients were included in the study. Of them, 66.9% were men and 31.3% were women. The compilation rate of the reporting forms was surprisingly high, considering that the final reporting form included 150 data points and that there were no independent personnel in charge of filling the forms. CONCLUSIONS Trauma registries are feasible even in health care systems where funding of medical research is sparse.

Methionine-Loading Rapidly Impairs Endothelial Function, by Mechanisms Independent of Endothelin-1: Evidence for an Association of Fasting Total Homocysteine with Plasma Endothelin-1 Levels

Objective: Homocysteinemia is associated with elevated oxidative stress and impaired endothelial function. In the present study we examined the impact of oxidative stress in the development of endothelial dysfunction in both chronic and acute (methionine-induced) homocysteinemia in humans. We also examined the role of endothelin-1 (ET-1) in the development of endothelial dysfunction in these two conditions. Methods: In this double-blind placebo controlled study, 28 subjects of both genders (14 with homocysteinemia and 14 healthy controls) underwent methionine-loading (100mg/Kg body weight) in a standard juice, containing vitamins C (2g) plus E (800IU) (n = 14) or no vitamins (placebo group, n = 14). Forearm vasodilatory response to reactive hyperemia, plasma total homocysteine (tHcy), oxidized LDL (ox-LDL), ET-1 and soluble vascular cell adhesion molecule (sVCAM-1), were evaluated at baseline and 4 hours post methionine loading (4hPML). Results: Chronic homocysteinemia was associated with increased oxLDL (p < 0.01), higher ET-1 (p < 0.05) and impaired endothelial function (p < 0.01). However, oxLDL (but not ET-1) was increased 4hPML in the placebo group, an effect prevented by antioxidant vitamins. The development of severe endothelial dysfunction 4hPML was not however prevented by antioxidants. In linear regression analysis, fasting tHcy was an independent predictor of baseline oxLDL (p = 0.0001), but not of ET-1 levels. On the contrary, oxLDL was the main predictor of ET-1 (p = 0.008), suggesting that tHcy may increase ET-1 by enhancing the production of oxLDL. Conclusions: Both chronic and acute methionine-induced homocysteinemia are associated with elevated oxidative stress status. Although ET-1 is increased in chronic homocysteinemia, it does not participate in the rapid development of endothelial dysfunction after methionine loading. These findings suggest that despite its potential role in chronic homocysteinemia, ET-1 has a limited contribution to the development of endothelial dysfunction in acute, methionine-induced homocysteinemia in humans.

Emergency room management of trauma patients in Greece: preliminary report of a national study.

AIM OF THE STUDY The aim of this study was to record and to evaluate the epidemiology of trauma in Greece and to assess the quality of management provided for trauma patients in the emergency department in Greek hospitals. METHODS The Hellenic Society of Trauma and Emergency Surgery invited all the official representatives of the society throughout the country to participate in the study. The representatives that responded positively, met with the Board of the society in succeeding meetings to establish the reporting form and the inclusion criteria. Inclusion criteria were defined as trauma patients requiring admission, transfer to a higher level center or arrived dead or died in the emergency department of the reporting hospital. All reports were accumulated by the Hellenic Trauma society, imported in an electronic data base and analyzed. The design of the study was prospective and observational. RESULTS In total 8862 patients were included in the study in 12 months time. Of them 68.7% (n=6084) were male, aged 41.8+/-20.6 (mean+/-S.D.) and 31.3% were female (n=2778), aged 52.7+/-24.1 (mean+/-S.D.). The mean duration of treatment in the emergency room department was 1h and 28min. Of the total number of patients, 2312 (26.1%) were initially assessed and managed by a specialist and 6249 (70.5%) were initially assessed and managed by a resident. CONCLUSIONS Data from this study show that there is substantial room for improvement in the patient care in the emergency department following trauma. Further evaluation will be required to identify particular management patterns that can be readily altered.

Exaggerated exercise blood pressure response is related to tissue Doppler imaging estimated diastolic dysfunction in the early stages of hypertension

We investigated the plausible interrelationship of exaggerated blood pressure response (EBPR) during exercise with left ventricular (LV) diastolic dysfunction, both associated with adverse cardiovascular outcomes, in the early stages of essential hypertension (EH). Sixty-five consecutive patients (aged 54 years, 56 males) with stage I to II EH underwent 24-hour ambulatory blood pressure (BP) recording and treadmill exercise testing and were classified as subjects with (n = 21) and without EBPR (n = 44) based on the systolic BP elevation at peak exercise (>/=210 mm Hg for men and >/=190 mm Hg for women). LV diastolic function was estimated by pulsed tissue Doppler imaging (TDI), averaging diastolic mitral annular velocities (Em, Am) from four separate sites (LV lateral, septal, anterior, and inferior wall). Hypertensives with EBPR, compared with those without EBPR, exhibited increased 24-hour pulse pressure by 4.8 mm Hg (P < .05) and significantly lower values of Em/Am ratio by 0.07 (P < .05). Univariate logistic regression analysis revealed that only 24-hour pulse pressure (odds ratio [OR] = 1.069; P = .043) and Em/Am (OR = 0.041; P = .049) were independent predictors of EBPR. Hypertensives with EBPR compared to their counterparts without EBPR are characterized by more pronounced LV diastolic dysfunction - assessed by TDI. Moreover, the increased pulsatile load seems to be a common denominator of these hypertension-linked states.

Novel Risk Factors Related to Stable Angina

Stable angina (SA) pectoris is a common and disabling disorder in patients with coronary artery disease (CAD), with increasing epidemiology and is associated with myocardial infarction and increased mortality. However, within the population of SA patients, an individuals prognosis can vary considerably. Except from conventional risk factors a variety of biomarkers have been evaluated for their prognostic significance in the settings of SA. Novel biomarkers associated with inflammatory status, such as C reactive protein and tumor necrosis factor alpha, with myocardial performance, such as B-type natriuretic peptide, with extracellular matrix remodeling, with vascular calcification such as osteoprotogerin and osteopontin, with myocardial ischemia, such as ischemia modified albumin have been associated with the progression of CAD and with the prognosis of SA patients. Despite the multiplicity of novel biomarkers there is lack of a clinical useful, highly specific for CAD biomarker with the ability to guide treatment decisions. In the context of this evidence in this review article we summarize the so far acquired knowledge of the most promising biomarkers and we discuss the major clinical correlations of novel risk factors with SA physical history, their predictive value for future cardiovascular events and their use in the treatment monitoring of this population.