Stefanos G. Foussas

The natural history of aneurysmal coronary artery disease.

OBJECTIVE: To assess the contribution of coronary artery ectasia, either isolated or in association with obstructive coronary artery disease, to morbidity and mortality from ischaemic heart disease. DESIGN: A retrospective study of patients undergoing coronary arteriography at a tertiary cardiac centre. PATIENTS AND METHODS: The epidemiological, clinical, arteriographic, and follow up characteristics of three groups of patients were examined: group A, 172 patients with coronary artery ectasia and coexisting significant coronary artery disease; group B, 31 patients with coronary artery ectasia only; group C, 165 patients with significant coronary artery disease but without ectasia, matched for sex and age with group A. RESULTS: Group A patients had a similar incidence of a previous myocardial infarction to group C patients (61.6% v 64.2%), exercise performance, severity of obstructive lesions (CASS score 2.19 v 2.14), and similar distribution of diseased vessels. At follow up of approximately two years they experienced a similar incidence of unstable angina (7.5% v 4.4%) and myocardial infarction plus cardiac death (4.9% v 6.1%). They underwent bypass surgery with similar frequency (39% v 42%) but there was a lower frequency of percutaneous transluminal coronary angioplasty (5.8% v 17%, P < 0.01). Patients with pure coronary ectasia (group B) had a lower incidence of a previous myocardial infarction (38.7%, 12/31, P < 0.05) than the two other groups. The infarct in all cases was related to an ectatic artery. Their exercise performance and ejection fraction (9 (SD 3) minutes and 56.5(9)%) were higher (P < 0.01) than group A (5 (2) minutes, 48.3(10)%) and group C (5.3 (2) minutes, 49.3(10)%). Group B had no myocardial infarctions, cardiac death, surgery, or intervention at follow up; 4.4% (5/115) developed unstable angina. The incidence of angina at study entry was similar in all three groups (38.7-49.7%). CONCLUSIONS: Coronary artery ectasia does not confer added risk in patients with coexisting obstructive coronary artery disease. Although there is a measurable incidence of previous myocardial infarction, patients with pure ectasia have a good prognosis. The wisdom of giving oral anticoagulants to such patients is questioned.

The impact of plasma levels of C-reactive protein, lipoprotein (a) and homocysteine on the long-term prognosis after successful coronary stenting: The global evaluation of new events and restenosis after stent implantation study

OBJECTIVES The objective of this study was to evaluate the association of high plasma levels of either C-reactive protein (CRP), lipoprotein (a) (Lp[a]) or total homocysteine (tHCY) with the long-term prognosis after successful coronary stenting (CS). BACKGROUND High plasma levels of either CRP, Lp(a) or tHCY may have an impact in coronary artery disease. However, long-term prospective data after coronary stenting (CS) are limited. METHODS Four-hundred and eighty-three consecutive patients with either stable or unstable coronary syndromes were followed for up to three years after successful CS. The composite of cardiac death, myocardial infarction or rehospitalization for rest unstable angina, whichever occurred first, was the prespecified primary end point. Moreover, the one-year incidence of clinical recurrence of symptoms, in-stent restenosis (ISR) and progression of atherosclerosis to a significant lesion (PTSL) were additionally evaluated. PTSL was defined as an increase by at least 25% in the luminal diameter stenosis of a known nonsignificant lesion (<or=50% luminal diameter stenosis) that was located in a nonintervened vessel at restudy, resulting in an angiographically significant lesion (>or=70% luminal diameter stenosis). RESULTS By the end of the follow-up, high plasma levels of either CRP or Lp(a) but not tHCY were independently associated with the primary end point. In particular, CRP >or=0.68 mg/dl (p < 0.001) or Lp(a) >or=25 mg/dl (p = 0.003) conferred a significantly increased risk. By 1 year, a CRP >or=0.68 mg/dl conferred a significantly increased risk for clinical recurrence of symptoms (p < 0.001) or PTSL (p < 0.001). None of the studied biochemical markers was related to ISR. CONCLUSIONS High plasma levels of either CRP or Lp(a) but not tHCY may be associated with a higher incidence of late adverse events after successful CS. PTSL in vessels not previously intervened upon may play a significant role in the underlying pathophysiology as opposed to ISR.

Multimarker strategy for the prediction of 31 days cardiac death in patients with acutely decompensated chronic heart failure

BACKGROUND To investigate the combined prognostic value of admission serum levels of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP), in patients hospitalized because of acutely decompensated severe (New York Heart Association class III/IV) low-output chronic heart failure (CHF). METHODS A total of 577 consecutive patients recruited in the 5 participating centers, were studied. Cardiac mortality by 31 days was the prespecified primary study end point. RESULTS A total of 102 (17.7%) patients died by 31 days. When the study patients were divided according to the number of elevated study biomarkers, there was a significant gradual increased risk of 31-day cardiac death with increasing in the number of elevated biomarkers (p<0.001). The value of the discriminant C statistic for the Cox regression analysis, increased significantly when each of the study biomarkers was incorporated with the other risk predictors into a Cox regression model, with the highest C statistic value for the Cox regression model that included all the study biomarkers (p<0.001). By multivariate Cox regression analysis, elevated serum levels of BNP (p=0.002), cTnI (p<0.001) and hs-CRP (p=0.02) were independent predictors of the study end point. CONCLUSIONS In conclusion, in patients hospitalized for acute decompensation of severe (NYHA III/IV) low-output CHF, BNP, cTnI and hs-CRP upon admission offers enhanced early risk stratification. With increasing number of elevated biomarkers, the risk of 31-day cardiac death increases gradually that implies treatment intensification, and closer follow-up.

Acute anterior myocardial infarction after multiple bee stings. A case of Kounis syndrome

A 58-year-old man with no history of cardiac diseases or cardiovascular risk factors was stung by honeybees. Soon after, he gradually developed signs of an allergic reaction followed by severe retrosternal pain. Electrocardiographic, echocardiographic evidence and positive biochemical markers were consistent with an acute anterolateral myocardial infarction. Coronary arteriography showed a left anterior descending artery thrombotic lesion. This is a case of Kounis syndrome, which is the concurrence of acute coronary syndromes with conditions associated with mast cell activation including allergic or hypersensitivity reactions as well as anaphylactic or anaphylactoid insults. The clinical implications and pathophysiology of this dangerous association are discussed.

The impact of treatment with omeprazole on the effectiveness of clopidogrel drug therapy during the first year after successful coronary stenting.

BACKGROUND Because clopidogrel is converted to its active metabolite by P450 isoenzymes, which are also involved in the metabolism of omeprazole, there is concern regarding whether the action of clopidogrel would be reduced in patients also taking omeprazole. OBJECTIVE To evaluate the impact of omeprazole administration on the effectiveness of clopidogrel drug therapy during the first year following successful coronary stenting (CS). METHODS A total of 588 consecutive patients who underwent successful CS for stable or unstable coronary artery disease were studied. Patients were classified into those who were treated (group A, n=340) or not treated (group B, n=248) with omeprazole for seven or more consecutive days during the entire observation period. The composite of cardiac death or rehospitalization for nonfatal myocardial infarction during the first year was the prespecified primary study end point. RESULTS Baseline characteristics, and dual clopidogrel and acetylsalicylic acid drug therapy were well balanced between the study groups. By one year, the primary end point was reached by 58 (9.9%) patients, including 20 (3.4%) who died due to cardiac reasons and 38 (6.5%) who were rehospitalized because of a nonfatal myocardial infarction. Patients in groups A and B, respectively, were at similar risk of the primary composite end point (10% versus 9.7%, hazard ratio 1.1 [95% CI 0.6 to 1.8]; P=0.89). CONCLUSIONS According to the results of the present study, treatment with omeprazole had no impact on the clinical efficacy of clopidogrel drug therapy during the first year after successful CS.

Toll/Interleukin-1 receptor member ST2 exhibits higher soluble levels in type 2 diabetes, especially when accompanied with left ventricular diastolic dysfunction

BackgroundSoluble ST2, a member of the of the Toll/IL-1 superfamily, is a novel biomarker with exceptional predictive value in heart failure and myocardial infarction- related mortality as well as in acute dyspneic states. Soluble ST2 is considered a decoy receptor of IL 33 that blocks the protective effects of the cytokine in atherosclerosis and cardiac remodeling. In the present study we investigated the differences in the levels of soluble ST2, BNP and hs-CRP between healthy controls and patients with type 2 diabetes with and without left ventricular diastolic dysfunction. A secondary aim was to investigate correlations between sST2 and other biomarkers of type 2 diabetes, such as HbA1c.Methods158 volunteers were recruited and underwent a complete Doppler-echocardiographic evaluation of both systolic & diastolic cardiac function. All subjects with ejection fraction < 50% were excluded. The study population was divided in 4 groups as follows: A: 42 healthy controls, B: 18 subjects without diabetes with LVDD, C: 48 patients with type 2 diabetes without LVDD & D: 50 patients with type 2 diabetes & LVDD. ELISA technique was performed to measure sST2 levels. Statistical analysis was performed with Kruskal-Wallis & Mann-Whitney test (continuous variables), chi squared & Fischer exact test (discrete variables), Spearman coefficient (univariate analysis) and step-wise backward method (multivariate analysis).ResultsPatients with type 2 diabetes with (p < 0.001) or without LVDD (p = 0.007) had higher serum ST2 levels compared to healthy controls, state found also for hs-CRP levels but not for the corresponding BNP levels (p = 0.213 & p = 0.207 respectively). Patients with type 2 diabetes & LVDD had higher serum ST2 in relation to diabetic patients without LVDD (p = 0.001). In multivariate analysis HbA1c positively and independently correlated with sST2 levels in both groups of patients with type 2 diabetes.ConclusionsPatients with type 2 diabetes exhibit higher sST2 levels compared to healthy controls. The presence of LVDD in patients with type 2 diabetes is associated with even higher sST2 levels. A significant correlation between glycemic control and sST2 levels was also revealed.

The paradoxical association of common polymorphisms of the renin-angiotensin system genes with risk of myocardial infarction.

Background The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) and the A1166C polymorphism of the angiotensin-II AT1 receptor (AT1R) have been extensively investigated as possible risk factors for myocardial infarction (MI). Design and methods Genetic association, case-control study, specifically designed to investigate the association of the above-mentioned polymorphisms with risk of MI in a homogeneous, low coronary risk, Caucasian population. The study population consisted of 1603 consecutive patients with acute MI who were recruited from nine clinics, located in three cities, and 699 unrelated adults who were randomly selected from the city catalogues. Results In univariate analysis, the DD genotype was found to be more prevalent among controls (40.8 vs. 35.2%, P = 0.011). In multivariate analysis adjusted for age, gender, smoking status, diabetes mellitus, hypercholesterolemia, hypertension and family history of coronary artery disease, the presence of the DD genotype was independently and negatively associated with risk of AMI (RR = 0.743, 95% CI = 0.595–0.927, P = 0.008). The CC genotype was not found to be significantly associated with risk of MI, either in univariate (6.2 vs. 6.4%, P = 0.856), or in multivariate analysis adjusted for the same confounders (RR = 0.743, 95% CI = 0.473–1.167, P = 0.197). Conclusions Contrary to previous reports, in this study the DD genotype of the ACE gene, but not the CC genotype of the AT1R gene, was associated with a lower risk of MI. Our results emphasize the complexity of genotype-phenotype interactions in the pathogenesis of ischaemic heart disease and question the previously hypothesized role of the DD genotype on risk of acute myocardial infarction.

Angiographic study of coronary artery disease in diabetic patients in comparison with nondiabetic patients.

Diabetes mellitus is known to be a major risk factor for the development of coronary artery disease (CAD). The aim of this study was to investigate angiographically the coronary arteries of diabetic persons, focusing on the type and distribution of CAD, sex differences in CAD anatomy, and the size of the coronary vessels. This was a randomized study and included two groups of patients with angiographically demonstrated CAD. Group A included 463 diabetics, aged 60.3 years, and Group B 210 nondiabetic patients, aged 58.5 years. The two groups were matched by age, sex, weight, and classic risk factors. The authors evaluated the regional location of CAD, left ventricular (LV) function, and the width of the lumen of coronary arteries. The diabetics had three-vessel disease more frequently (p < 0.001) and one-vessel disease less frequently (p < 0.001). The CAD was more extensive in Group A (mean 2.2 vessels, compared to 1.8 vessels in Group B, p < 0.01). The right coronary artery was affected more often in diabetics (p < 0.01), as was the anterior descending artery in three-vessel disease (p < 0.05). The male diabetics had the same angiographic CAD severity as the females, although the latter had a better LV ejection fraction (p < 0.05). The female diabetics < 55 years old had CAD findings comparable with those from women 4 years older in Group B. Diabetics show more diffuse and severe CAD than the general population. There are no sex-related differences in the severity of CAD.

Diabetic myocardial disease: pathophysiology, early diagnosis and therapeutic options

Diabetes mellitus is a powerful risk factor for cardiovascular disease associated with high morbidity and mortality rates. Diabetic patients also have an increased incidence of heart failure which has been traditionally attributed to the concurrent presence of ischemic or hypertensive heart disease. Yet, nowadays, according to recent scientific evidence, diabetic myocardial disease (DMD) is more and more being considered as a distinct nosologic entity, independent of the co-existence of coronary artery disease, arterial hypertension or other risk factors, with the potential to lead to a self-existent progressive development of heart failure. In this article, we review the possible pathophysiologic mechanisms involved in the development of DMD as well as the structural and functional changes in the diabetic heart. We emphasize the importance of early detection of the syndrome, especially by novel echocardiographic techniques. Finally, we refer to the various therapeutic options for the optimal management of DMD according to the recent literature.

Plasma asymmetric dimethylarginine and mortality in patients with acute decompensation of chronic heart failure

Objectives To investigate the prognostic value of circulating levels of asymmetric dimethylarginine (ADMA) in patients with acute decompensation of (New York Heart Association (NYHA) class III/IV) chronic heart failure and reduced left ventricular ejection fraction. Design Single-centre prospective observational study. Setting Tertiary referral centre. Patients A total of 651 consecutive and eligible hospitalised patients were studied. Patients were divided into four groups according to the quartiles of circulating levels of ADMA upon presentation. Main outcome measures Incidence of in-hospital (or 7-day in the case of prolonged hospitalisation), 31-day and 1-year cardiac mortality were the pre-specified study end points. Results Cumulative rates of in-hospital, 31-day and 1-year cardiac mortality were 10.6%, 18.7% and 36.4%, respectively. There was a gradual increased risk of in-hospital (pfor trend=0.011), 31-day (pfor trend=0.044) and 1-year (pfor trend<0.001) mortality with increasing ADMA quartiles. After adjustment for possible confounders, patients at the highest ADMA quartile were at significantly higher risk for in-hospital (p=0.042), 31-day (p=0.032) and 1-year (p<0.001) mortality than those in the lowest quartile. Conclusions According to the present results, an elevated circulating level of ADMA is a strong independent predictor of short-term and long-term mortality in patients with acute decompensation of NYHA class III/IV chronic heart failure and reduced left ventricular ejection fraction. ADMA levels upon presentation may confer enhanced risk stratification in this setting.