Traitements des facteurs de risque cardiovasculaire et dépistage de la maladie coronarienne dans le diabète de type 2 [Treatments for cardiovascular risk factors and screening for coronary artery disease in type 2 diabetes mellitus]

The recent ACCORD and DIAD studies revealed results which could modify treatments and the screening of diabetes vascular complications. Indeed, ACCORD shows no benefit on the prevention of diabetes vascular complications by aggressive treatment of hypertension or the combined treatment of the dyslipidemia. The intensive treatment of the blood glucose, if associated with severe hypoglycemias, increases mortality. DIAD revealed 20% of silent myocardial ischaemia in diabetic patients but no beneficial effect on the cardiovascular mortality. A careful reading of these studies in the light of long term studies such as UKPDS and STENO reveals that these negative results are generated by a too short follow-up and too aggressive objectives. The long term studies reveal that more realistic objectives remain beneficial.

Regional coronary endothelial function is closely related to local early coronary atherosclerosis in patients with mild coronary artery disease: pilot study.

BACKGROUND: Coronary endothelial function is abnormal in patients with established coronary artery disease and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the noninvasive assessment of both anatomic and functional (endothelial function) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endothelial function is related to measures of early atherosclerosis such as increased coronary wall thickness. METHODS AND RESULTS: Seventeen arteries in 14 healthy adults and 17 arteries in 14 patients with nonobstructive coronary artery disease were studied. To measure endothelial function, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor, and changes in coronary cross-sectional area and flow were measured. Black blood imaging was performed to quantify coronary wall thickness and indices of arterial remodeling. The mean stress-induced change in cross-sectional area was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2%±6.8%, P<0.0001, n=17). Mean coronary wall thickness was lower in healthy subjects (0.9±0.2 mm) than in patients with coronary artery disease (1.4±0.3 mm, P<0.0001). In contrast to healthy subjects, stress-induced changes in cross-sectional area, a measure of coronary endothelial function, correlated inversely with coronary wall thickness in patients with coronary artery disease (r=-0.73, P=0.0008). CONCLUSIONS: There is an inverse relationship between coronary endothelial function and local coronary wall thickness in patients with coronary artery disease but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.

Contribution of major cardiovascular risk factors to familial premature coronary artery disease : the GENECARD project

Résumé Objectifs: Cette étude relève la prévalence des principaux facteurs de risque cardiovasculaire dans les coronaropathies précoces (P-CAD) familiales, survenant chez au moins deux frères et/ou soeurs d'une même fratrie. Méthodes: Nous avons recruté 213 survivants atteints de P-CAD, issus de 103 fratries, diagnostiqués avant l'âge de 50 ans chez les hommes et 55 ans chez les femmes. La présence ou non d'hypertension, d'hypercholestérolémie, d'obésité et de tabagisme a été documentée au moment de l'événement chez 163 de ces patients (145 hommes et 18 femmes). Chaque patient a été comparé à deux individus de même âge et sexe, chez qui un diagnostic de P-CAD «sporadique» (non familiale) était posé, et à trois individus choisis au hasard parmi la population générale. Résultats: En comparaison de la population générale, les patients atteints de P-CAD sporadique avaient une prévalence supérieure pour l 'hypertension (29% vs. 14%, p<0.001), le cholestérol (54% vs. 33%, p<0.001), l'obésité (20% vs. 13%, p<0.001) et le tabagisme (76% vs. 39%, p<0.001). Ces facteurs de risque étaient de prévalences similaires, voire supérieures chez les patients atteints de P-CAD familiale (43% [p0.05 vs. P-CAD sporadiques], 58% [p=0.07], 21% et 72% respectivement). Seulement 7 (4%) des 163 patients atteints de P-CAD familiale et 22 (7%) des 326 patients atteints de P-CAD sporadique, ne présentaient aucun facteur de risque cardiovasculaire, comparés à 167 (34%) des 489 patients issus de la population générale. Conclusions: Les facteurs de risque cardiovasculaire classiques et réversibles ont une haute prévalence chez les patients atteints de P-CAD familiale. Ce fait rend improbable une contribution génétique prédominante, agissant en l'absence de facteurs de risque. Summary Objectives: This study was designed to assess the prevalence of major cardiovascular risk factors in familial premature coronary artery disease (P-CAD), affecting two or more siblings within one sibship. Background: Premature CAD has a genetic component. It remains to be established whether familial P-CAD is due to genes acting independently from major cardiovascular risk factors. Methods: We recruited 213 P-CAD survivors from 103 sibships diagnosed before age ?50 (men) or ?55 (women) years old. Hypertension, hypercholesterolemia, obesity, and smoking were documented at the time of the event in 163 patients (145 men and 18 women). Each patient was compared with two individuals of the same age and gender, diagnosed with sporadic (nonfamilial) P-CAD, and three individuals randomly sampled from the general population. Result: Compared with the general population, patients with sporadic P-CAD had a higher prevalence of hypertension (29% vs. 14%, p < 0.001), hypercholesterolemia (54% vs. 33%, p < 0.001), obesity (20% vs. 13%, p < 0.01), and smoking (76% vs. 39%, p < 0.001). These risk factors were equally or even more prevalent in patients with familial P-CAD (43% [p < 0.05 vs. sporadic P-CAD], 58% [p = 0.07], 21% and 72%, respectively). Overall, only 7 (4%) of 163 of patients with familial P-CAD and 22 (7%) of 326 of patients with sporadic P-CAD had none of these conditions, as compared with 167 (34%) of 489 patients in the general population. Conclusions: Classic, remediable risk factors are highly prevalent in patients with familial P-CAD. Accordingly, a major contribution of genes acting in the absence of these risk factors is unlikely.

Improved coronary artery definition with T2-weighted, free-breathing, three-dimensional coronary MRA.

BACKGROUND: Three-dimensional (3D) navigator-gated and prospectively corrected free-breathing coronary magnetic resonance angiography (MRA) allows for submillimeter image resolution but suffers from poor contrast between coronary blood and myocardium. Data collected over >100 ms/heart beat are also susceptible to bulk cardiac and respiratory motion. To address these problems, we examined the effect of a T2 preparation prepulse (T2prep) for myocardial suppression and a shortened acquisition window on coronary definition. METHODS AND RESULTS: Eight healthy adult subjects and 5 patients with confirmed coronary artery disease (CAD) underwent free-breathing 3D MRA with and without T2prep and with 120- and 60-ms data-acquisition windows. The T2prep resulted in a 123% (P<0. 001) increase in contrast-to-noise ratio (CNR). Coronary edge definition was improved by 33% (P<0.001). Acquisition window shortening from 120 to 60 ms resulted in better vessel definition (11%; P<0.001). Among patients with CAD, there was a good correspondence with disease. CONCLUSIONS: Free-breathing, T2prep, 3D coronary MRA with a shorter acquisition window resulted in improved CNR and better coronary artery definition, allowing the assessment of coronary disease. This approach offers the potential for free-breathing, noninvasive assessment of the major coronary arteries.

Fonction ventriculaire gauche après revascularisation pour occlusion d'une coronaire d'une durée de 1-2 heures [Left ventricular function following revascularization for occlusion of a coronary artery lasting 1 to 2 hours].

The time-lag between coronary occlusion and irreversible damage to the myocardium is ill-defined in man. In 10 patients the changes in left ventricular function have been studied after coronary occlusion during diagnostic or therapeutic cardiac catheterization of 1-2 hours' duration. Revascularization was achieved either surgically or through intracoronary streptokinase infusion. The interval between occlusion and onset of extracorporal circulation or reopening was 61 to 119 minutes. Despite enzyme elevation (CPK, CK-MB, SGOT) and appearance of Q-waves in 5 patients, no significant alteration of left ventricular function was noted on repeat cardiac catheterization 10 to 230 days after the accident. These observations, suggest that coronary occlusion of 1-2 hours' duration fails to produce significant irreversible damage to the myocardium despite electrocardiographic and enzymatic signs of myocardial infarction.

Acetaminophen increases blood pressure in patients with coronary artery disease.

BACKGROUND: Because traditional nonsteroidal antiinflammatory drugs are associated with increased risk for acute cardiovascular events, current guidelines recommend acetaminophen as the first-line analgesic of choice on the assumption of its greater cardiovascular safety. Data from randomized clinical trials prospectively addressing cardiovascular safety of acetaminophen, however, are still lacking, particularly in patients at increased cardiovascular risk. Hence, the aim of this study was to evaluate the safety of acetaminophen in patients with coronary artery disease. METHODS AND RESULTS: The 33 patients with coronary artery disease included in this randomized, double-blind, placebo-controlled, crossover study received acetaminophen (1 g TID) on top of standard cardiovascular therapy for 2 weeks. Ambulatory blood pressure, heart rate, endothelium-dependent and -independent vasodilatation, platelet function, endothelial progenitor cells, markers of the renin-angiotensin system, inflammation, and oxidative stress were determined at baseline and after each treatment period. Treatment with acetaminophen resulted in a significant increase in mean systolic (from 122.4±11.9 to 125.3±12.0 mm Hg P=0.02 versus placebo) and diastolic (from 73.2±6.9 to 75.4±7.9 mm Hg P=0.02 versus placebo) ambulatory blood pressures. On the other hand, heart rate, endothelial function, early endothelial progenitor cells, and platelet function did not change. CONCLUSIONS: This study demonstrates for the first time that acetaminophen induces a significant increase in ambulatory blood pressure in patients with coronary artery disease. Thus, the use of acetaminophen should be evaluated as rigorously as traditional nonsteroidal antiinflammatory drugs and cyclooxygenase-2 inhibitors, particularly in patients at increased cardiovascular risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00534651.

Coronary artery imaging by magnetic resonance.

Non-invasive visualization of the coronary arteries represents a major challenge in modern cardiology, but this goal may be achieved in the near future by MR angiography. Possible applications are non-invasive diagnosis of coronary artery disease, and follow-up examinations for therapy control after PTCA, in order to detect restenosis at an early stage. A multiple slice technique (2 mm slice thickness, with a spatial resolution of 1 x 1 mm, Philips Gyroscan ACS-II, 1.5 Tesla) was used. Ten volunteers were imaged and 10 patients with coronary artery disease were examined before and after PTCA. MR measurements were validated by quantitative coronary angiography. The diameters of the proximal coronary arteries as measured by both methods were compared, and a good correlation was found (r = 0.76). Thus, it is concluded that non-invasive visualization of the coronary arteries is possible before and after PTCA and allows to determine potential restenoses. However, patient cooperation is essential for good image quality. Moreover, limited spatial image resolution and breathing artifacts restrict MR coronary angiography today to be used as a routine diagnostic tool for the diagnosis of coronary artery disease.

MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single-photon emission computed tomography for the detection of coronary artery disease: a comparative multicentre, multivendor trial.

Aims Perfusion-cardiac magnetic resonance (CMR) has emerged as a potential alternative to single-photon emission computed tomography (SPECT) to assess myocardial ischaemia non-invasively. The goal was to compare the diagnostic performance of perfusion-CMR and SPECT for the detection of coronary artery disease (CAD) using conventional X-ray coronary angiography (CXA) as the reference standard. Methods and results In this multivendor trial, 533 patients, eligible for CXA or SPECT, were enrolled in 33 centres (USA and Europe) with 515 patients receiving MR contrast medium. Single-photon emission computed tomography and CXA were performed within 4 weeks before or after CMR in all patients. The prevalence of CAD in the sample was 49%. Drop-out rates for CMR and SPECT were 5.6 and 3.7%, respectively (P = 0.21). The primary endpoint was non-inferiority of CMR vs. SPECT for both sensitivity and specificity for the detection of CAD. Readers were blinded vs. clinical data, CXA, and imaging results. As a secondary endpoint, the safety profile of the CMR examination was evaluated. For CMR and SPECT, the sensitivity scores were 0.67 and 0.59, respectively, with the lower confidence level for the difference of +0.02, indicating superiority of CMR over SPECT. The specificity scores for CMR and SPECT were 0.61 and 0.72, respectively (lower confidence level for the difference: -0.17), indicating inferiority of CMR vs. SPECT. No severe adverse events occurred in the 515 patients. Conclusion In this large multicentre, multivendor study, the sensitivity of perfusion-CMR to detect CAD was superior to SPECT, while its specificity was inferior to SPECT. Cardiac magnetic resonance is a safe alternative to SPECT to detect perfusion deficits in CAD.

Non-invasive detection of coronary endothelial response to sequential handgrip exercise in coronary artery disease patients and healthy adults.

OBJECTIVES: Our objective is to test the hypothesis that coronary endothelial function (CorEndoFx) does not change with repeated isometric handgrip (IHG) stress in CAD patients or healthy subjects. BACKGROUND: Coronary responses to endothelial-dependent stressors are important measures of vascular risk that can change in response to environmental stimuli or pharmacologic interventions. The evaluation of the effect of an acute intervention on endothelial response is only valid if the measurement does not change significantly in the short term under normal conditions. Using 3.0 Tesla (T) MRI, we non-invasively compared two coronary artery endothelial function measurements separated by a ten minute interval in healthy subjects and patients with coronary artery disease (CAD). METHODS: Twenty healthy adult subjects and 12 CAD patients were studied on a commercial 3.0 T whole-body MR imaging system. Coronary cross-sectional area (CSA), peak diastolic coronary flow velocity (PDFV) and blood-flow were quantified before and during continuous IHG stress, an endothelial-dependent stressor. The IHG exercise with imaging was repeated after a 10 minute recovery period. RESULTS: In healthy adults, coronary artery CSA changes and blood-flow increases did not differ between the first and second stresses (mean % change ±SEM, first vs. second stress CSA: 14.8%±3.3% vs. 17.8%±3.6%, p = 0.24; PDFV: 27.5%±4.9% vs. 24.2%±4.5%, p = 0.54; blood-flow: 44.3%±8.3 vs. 44.8%±8.1, p = 0.84). The coronary vasoreactive responses in the CAD patients also did not differ between the first and second stresses (mean % change ±SEM, first stress vs. second stress: CSA: -6.4%±2.0% vs. -5.0%±2.4%, p = 0.22; PDFV: -4.0%±4.6% vs. -4.2%±5.3%, p = 0.83; blood-flow: -9.7%±5.1% vs. -8.7%±6.3%, p = 0.38). CONCLUSION: MRI measures of CorEndoFx are unchanged during repeated isometric handgrip exercise tests in CAD patients and healthy adults. These findings demonstrate the repeatability of noninvasive 3T MRI assessment of CorEndoFx and support its use in future studies designed to determine the effects of acute interventions on coronary vasoreactivity.

EACTS Day in the new EACTS House.

There is no doubt that the European Association for Cardio-Thoracic Surgery is a success story. In 2011, we celebrated the 25th anniversary of this professional organization. In 2012, we will celebrate the 25th anniversary of the European Journal of Cardio-Thoracic Surgery. In addition, two other journals have been initiated, Interactive CardioVascular and Thoracic Surgery and the Multimedia Manual of Cardio-Thoracic Surgery, and all of them can be accessed through CTSnet (www.ctsnet.org). The most recent development was the birth of EACTS House, and it was to celebrate the official opening of EACTS House on 10 February 2011, that we held the second Strategic meeting, 'EACTS in the Future'. On this occasion, the EACTS council and delegates of the EACTS Domains (Domain of Thoracic Disease, Domain of Vascular Disease, Domain of Congenital Cardiac Disease and Domain of Adult Cardiac Disease) came together with representative thoracic and cardio-vascular surgeons from North America, Asia and BRICS countries as well as senior managers from industry in order to decide where to go from there. As a basis for starting the discussions, a sector analysis of the activities of the Department of Cardio-Vascular Surgery at CHUV in Lausanne, Switzerland was performed in order to identify the trends in the activities of our group of surgeons by pulling the consolidated data for the period running from 1 January 1995 to 31 December 2010. Interestingly enough, the most frequent procedures like coronary artery bypass graft and valve repair/replacement did not increase despite a growing programme. In our setting, the compensation came mainly from vascular surgery and mechanical circulatory support. These data have to be put in perspective by the reports provided by the EACTS domain chairs in order to identify the challenges and opportunities for the future development of our specialties.