[Demographic evolution, clinical characteristics and in-hospital outcomes of older adults treated by primary angioplasty for ST-segment elevation myocardial infarction]. / Évolution démographique, caractéristiques et suivi clinique intrahospitalier des sujets âgés traités par angioplastie primaire pour syndrome coronarien aigu avec sus-décalage du segment ST.

BACKGROUND: The number of older adults treated for ST-segment elevation myocardial infarction (STEMI) is increasing. Nevertheless, their treatment might not be as optimal as younger adults. This study sought to evaluate demographic evolution, clinical characteristics and in-hospital outcomes of patients of patients aged 75years-old or older treated by primary angioplasty for STEMI. METHODS: Retrospective study of all consecutive patients for STEMI between January 2012 and December 2017. Their clinical, biologic, echocardiographic and angiographic data, as well as in-hospital outcomes were collected and compared between two groups: younger and older than 75 year-olds. RESULTS: Five hundred and sixty-eight patients including 99 (17.4%) 75 year-old or older were included in the present study. Patients aged 75 or older had an increased delay of treatment between the time of the chest pain onset and revascularization (7.30±1,16 vs 4.77±0,36hours, P=0.0391), they were more frequently treated with clopidogrel rather than more potent anti P2Y12 antiplatelet therapies (55.6% vs 24.8%, P<0.0001) and received less frequently anti-GP2B3A therapy (44.8% vs 23.2%, P<0.0001). There was a trend for increased in-hospital mortality in the older group, despite non statistically significant (4.04% vs 1.5%, P=0.0847). Older adults had a worse clinical status with decreased post-STEMI left ventricular ejection fraction (44.42±1,38 vs 49.07±0,49, P=0,0019). They were also less treated with drug-eluting stents (51.5% vs 73.9%, P<0.0001). CONCLUSION: Adults aged 75 years-old or older represent a subsequent proportion of patients admitted for STEMI. They had a worse initial clinical presentation associated with worse prognostic, as compared to younger adults. They experience delayed reperfusion therapy and suboptimal treatment as compared to younger adults.

[Antiplatelet duration in the elderly patients after percutaneous coronary intervention]. / Durée du traitement antiagrégant plaquettaire chez le sujet âgé stenté.

Ischemic heart disease is a leading cause of death in Europe. At the same time, older patients are at high risk for coronary heart disease and represent an increasing proportion of patients in the catheterization laboratory in the context of an ageing population. The elderly patients are also at higher bleeding risk, and were poorly represented in major randomized trials. Duration of dual antiplatelet therapy (DAPT), after percutaneous coronary intervention (PCI) should be modulated in a personalized way taking into account hemorrhagic and ischemic risk factors, using risk scores based on the latest recommendations of the European Society of Cardiology. Even if the optimal duration of DAPT after PCI is 6 months in case of stable coronary disease and 12 months in case of an acute coronary syndrome, it can be drastically reduced, up to one month in case of high hemorrhagic risk, or can be prolonged for more than 12 months in case of high ischemic risk. The use of latest generation drug eluting stents associated with a short duration of DAPT has thus demonstrated its safety compared to these durations. In case of triple therapy treatment, associating DAPT and anticoagulation therapy, DAPT is recommended to be as short as possible, potentially reduced to 1 month. Finally, the concomitant prescription of proton pump inhibitor is essential to prevent gastrointestinal bleedings. This literature review will discuss the hemorrhagic risk stratification and choice of DAPT in elderly patients.

[Diabetes Mellitus, a prothrombotic disease]. / Le diabète, une pathologie prothrombotique.

In patients with acute atherothrombotic disease, diabetes or glucose intolerance is frequently found. Indeed, the number of people with diabetes in the world continues to increase and is expected to reach more than 500 million people by 2035. Diabetes is a pathology commonly associated with both microvascular and macrovascular complications. Although the mortality of coronary artery disease has decreased significantly over the past 20 years, mortality in patients with type 2 diabetes has changed little and atherothrombotic events remain the leading cause of death in diabetic patients. Although our understanding of vascular pathology has greatly evolved in recent years, the cellular and molecular mechanisms linking thrombogenicity and diabetes remain incompletely understood. Type 1 and type 2 diabetes are prothrombotic pathologies. This prothrombotic state is due to both hyperglycemia and chronic hyperinsulinism. Among the different agonists involved in the increased thrombogenicity of diabetic patients, abnormalities can be found in all phases of coagulation. Increased procoagulant factors and tissue factor associated with impaired fibrinolysis, platelet hyperreactivity, endothelial dysfunction, leukocyte activation, low-grade inflammation, and microparticle involvement, they all play a role in the establishment of this prothrombotic condition. This review sought to provide an update on the prothrombotic nature of diabetes and its consequences in therapeutics.

Optimal time for catheterization in NSTE-ACS patients with impaired renal function: insights from the ABOARD Study.

BACKGROUND: To assess the impact of impaired renal function (IRF) and timing of catheterization (immediate versus delayed intervention) on outcomes in intermediate/high risk NSTE-ACS patients. METHODS: We performed a post-hoc analysis of the randomized ABOARD population to compare 1) patients with vs. without IRF and 2) the two intervention strategies in patients with IRF. A creatinine clearance <60 mL/min defined IRF. The primary endpoint was the in-hospital peak troponin I value; the secondary endpoints were a) the composite of death, myocardial infarction, urgent revascularization or recurrent ischemia (death/MI/UR/RI) and b) STEEPLE major bleeding (MB) at 1-month follow-up. RESULTS: Among the 345 patients, 75 (21.7%) had IRF. Patients with IRF were older, had more comorbidities and were at higher cardiovascular risk. Radial catheterization was predominant (84%). Among IRF patients, 37 (49%) and 38 (51%) patients were randomized to an immediate and delayed strategy, respectively. The primary and secondary endpoints rates were not different for the two comparisons. IRF was associated with more death (5.3% vs. 1.1%, p=0.043) and non-CABG MB (9.3% vs. 2.2%, p=0.001). In patients with IRF, a delayed strategy was associated with more recurrent ischemia (28.9% vs. 8.1%, p=0.021). Absence of clopidogrel pretreatment, insulin therapy and left main culprit lesion were independently associated with death/MI/UR/RI, while age and CABG surgery were related with MB. CONCLUSION: IRF is associated with worse outcomes in NSTE-ACS patients. The primary results of the ABOARD study apply also to patients with IRF in which the timing of catheterization does not impact hard outcomes.

Acute myocardial infarction secondary to platelet apheresis in a 57-year healthy donor.

Platelet donation by plateletpheresis is known to induce platelet and coagulation activation but there is no clear relationship between this acquired pre-thrombotic state and acute coronary syndrome in healthy donors. We report an acute myocardial infarction immediately following plateletpheresis in a 57-year-old donor with low atherosclerotic risk profile and no angiographic evidence of atherosclerotic disease strongly suggesting a causal relationship.

[Thromboaspiration in primary angioplasty for ST elevation myocardial infarction]. / Thrombo-aspiration dans l'infarctus du myocarde aigu avec sus-décalage du segment ST.

Primary angioplasty is the gold standard for myocardial reperfusion in patients with acute myocardial infarction with ST elevation (STEMI). Fast normalization of infarct-related coronary artery flow and no reflow prevention are correlated with clinical outcomes. Over the last years, many antithrombotic regimens have been evaluated in this setting. The use of a combined pharmacological and mechanical strategy with abciximab, and thromboaspiration of atherothrombotic debris is associated with coronary flow improvement, improvement of myocardial perfusion, and, in fine a better clinical outcome. In this respect, the current guidelines recommend a systematic manuel catheter thromboaspiration of the culprit lesion in STEMI with a class IIa, level of evidence A indication.

[Coronary artery implantation and course abnormalities: the contribution of multislice CT]. / Anomalies d'implantation et de trajet des artères coronaires: apport du scanner multicoupe.

Abnormalities in coronary artery origin and course are rare and often asymptomatic. However, visualizing them is of great interest because they can be responsible for iatrogenic trauma during cardiac surgery, and, for some of them, for myocardial infarction, which can lead to sudden death. We show the contribution of multislice CT in the positive diagnosis of these anatomic variations and in the differential diagnosis between benign and malignant forms, potentially responsible for myocardial ischemia.

[Management of chest pain by the Emergency Ambulance Service: the DOLORES register]. / Prise en charge de la douleur thoracique par le SAMU: le registre DOLORES.

Pre-hospital management of chest pain is a difficult problem. The emergency doctor has to take triage decisions based on instantaneous data whereas the decisional rationale of the many pathologies concerned, including acute coronary syndromes, is often based on observation over several hours. There have been few studies of the efficacy of pre-hospital management of chest pain by an emergency ambulance service. Therefore, the DOLORES register was set up to assess this problem over a 6 month period by the emergency ambulance service of Necker Hospital in Paris. Between January and June 2004, the Necker emergency ambulance service was called out on 205 occasions for chest pain. Forty-three patients had acute coronary syndromes (ACS) with ST elevation. Of the remaining 162 patients, 32 stayed at home, 2 were admitted the following day by cardiologists for coronary angiography, 52 were admitted for observation to the emergency unit and 76 were admitted to the coronary care unit. In the latter two groups, the final diagnosis of ACS without ST elevation was retained in 11/52 and 57/76 patients respectively. Finally, 2 patients were admitted directly to the catheter laboratory. The clinical and paraclinical data noted by the emergency ambulance service and at hospital admission was concordant in all cases. Pre-hospital triage by the emergency ambulance service seems to be effective. These results require confirmation with a large scale study.

[Prevalence of asymptomatic atherothrombotic lesions and risk of vascular events in patients with a stroke]. / Prévalence des lesions athérothrombotiques asymptomatiques et risque d'evénements vasculaires chez un patient ayant eu un accident vasculaire cérébral.

OBJECTIVE: To estimate the prevalence of asymptomatic atherothrombotic lesions and the absolute risk of vascular events in patients with ischemic stroke. METHODS: We conducted a systematic review of studies published between 1980 and 2004 which allowed calculating prevalence of asymptomatic lesions and absolute risks of vascular events in stroke patients. Studies included in the review of absolute risks had to include at least 100 patients followed for at least 1 year and with less than 5% of lost to follow-up. RESULTS: Coronarography was used in only one study which does not provide any precise estimation of the prevalence of asymptomatic coronary lesions. Depending on the population and the method used for the diagnosis of coronary disease, the prevalence of asymptomatic coronary artery disease ranged from 25 through 60%. Very few studies have been devoted to the prevalence of abdominal aortic disease in stroke patients. The prevalence of abdominal aortic aneurysm has been estimated to 1% and that of peripheral arterial disease to 10%. Thirty-six cohorts were identified. The absolute risk of myocardial infarction was about 2%/year and that of vascular death 2%/year. CONCLUSION: Stroke patients carry a high risk of coronary and vascular events. Additional studies are required to better identify patients with a high prevalence of asymptomatic atherosclerotic lesions and with a high risk of vascular events.

[Screening strategies for the diagnosis of asymptomatic arterial lesions in patients with atherothrombosis]. / Méthodes de dépistage des localisations artérielles asymptomatiques chez le patient athérothrombotique.

Atherosclerosis is a ubiquitous inflammatory disease. Patients presenting an acute atherothrombotic event (acute coronary syndrom, stroke, aortic aneurysm, ...) have an increased risk of events in remote arterial territories affected by atherosclerosis. These patients could benefit from systematic screening of asymptomatic atherosclerotic lesions to avoid these complications. For each atherosclerotic territory (coronary artery, carotid artery, aorta, peripheral arteries including renal arteries), we review the methods for screening asymptomatic atherothrombotic lesions which could justify specific treatments: coronary artery stenosis > or = 50%, carotid artery stenosis > or = 60%, renal artery stenosis > or = 50%, and abdominal aortic aneurysm > or = 30 mm. This review shows that non invasive methods (ie, echography, tomodensitometry) are widely available for diagnosis of asymptomatic lesions in carotid and renal arteries, and in the aorta. Despite its invasive caracteristic, coronarory angiography remains the gold-standard for the diagnosis of coronary artery disease. However, cardiac multi-slices CT-scan appears a promising technique for asymptomatic patients.

L-arginine administration reduces neointima formation after stent injury in rats by a nitric oxide-mediated mechanism.

The clinical outcome of vascular stenting is limited by in-stent stenosis. Increased nitric oxide (NO)/cGMP signaling by L-arginine (L-Arg) supplementation, the substrate for NO synthase (NOS), or NOS gene transfer may reduce in-stent neointima formation. After stenting, vascular cell proliferation in rat carotid arteries, as measured by 5'-bromodeoxyuridine (5'-BrdU) incorporation, indicated 15+/-8%, 28+/-5%, and 33+/-7% 5'-BrdU-positive vascular cells at 4, 7, and 14 days, respectively. Reporter beta-galactosidase gene transfer efficacy was evidenced by 30% beta-galactosidase-expressing medial smooth muscle cells at 14 days. The intima-to-media ratio (I/M) progressively increased to 2.32+/-0.24 at 14 days. To target in-stent neointima formation, animals were infected with adenoviral vectors (4x10(10) plaque-forming units per mL) expressing NOS2 (AdNOS2) or no transgene (AdRR5), or they received daily doses of L-Arg (500 mg. kg(-1). (d-1) IP). The neointima at 14 days was smaller in L-Arg-treated than in untreated rats (I/M 1.25+/-0.35 vs 2.32+/-0.24, P<0.05, n=7 each) or in AdRR5- and AdNOS2-infected rats (I/M 2.57+/-0.43, n=7 and 1.82+/-0.75, n=8, respectively; P<0.05 for both). The effect of L-Arg was abolished by simultaneous administration of N(G)-nitro L-arginine methyl ester, an NOS inhibitor (2.03+/-0.39, P<0.05, vs L-Arg). Inflammation was markedly less in L-Arg- and AdNOS2-treated than in AdRR5-infected rats. Supplemental L-Arg reduces neointima formation after stenting by way of an NOS-dependent mechanism and may be a valuable strategy to target in-stent stenosis.

Soluble guanylate cyclase alpha(1) and beta(1) gene transfer increases NO responsiveness and reduces neointima formation after balloon injury in rats via antiproliferative and antimigratory effects.

In vascular smooth muscle cells, NO stimulates the synthesis of cGMP by soluble guanylate cyclase (sGC), a heterodimer composed of alpha(1) and beta(1) subunits. NO/cGMP signal transduction affects multiple cell functions that contribute to neointima formation after vascular injury. Balloon-induced vascular injury was found to decrease sGC subunit expression and enzyme activity in rat carotid arteries. The effect of restoring sGC enzyme activity on neointima formation was investigated using recombinant adenoviruses specifying sGC alpha(1) and beta(1) subunits (Adalpha1 and Adbeta1). Coinfection of cultured rat aortic smooth muscle cells with Adalpha1 and Adbeta1 increased NO-stimulated intracellular cGMP levels 60-fold and decreased DNA synthesis and migration by 16% and 48%, respectively. Immunoreactivity for alpha(1) and beta(1) subunits colocalized in carotid arteries infected with Adalpha1 and Adbeta1. Molsidomine-stimulated carotid tissue cGMP levels were greater after coinfection with Adalpha1 and Adbeta1 than after infection with a control virus, AdRR5 (0.53+/-0.09 pmol/mg protein, mean+/-SEM, versus 0.23+/-0.09, P<0.05). Mean intima/media ratio, 2 weeks after balloon injury and twice-daily administration of 5 mg/kg molsidomine, was less in rats coinfected with Adalpha1 and Adss1 than in rats infected with AdRR5 or in uninfected rats (0.36+/-0.11 versus 0. 81+/-0.13 and 0.75+/-0.25, respectively, P<0.05). Thus, Adalpha1 and Adbeta1 gene transfer to balloon-injured rat carotid arteries increases NO responsiveness and attenuates neointima formation via a direct antiproliferative and antimigratory effect on vascular smooth muscle cells.

[Indications for intravenous GPIIb/IIIa receptor inhibitors in acute coronary syndrome without prolonged ST syndrome]. / Indications des inhibiteurs des récepteurs GP IIb/IIIa par voie intraveineuse dans les syndromes coronaires aigus sans sus-décalage du segment ST.

Platelet adhesion and aggregation play a pivotal role in the physiopathology of acute coronary syndromes. Inhibitors of the GPIIb/IIIa receptors block the final step of platelet aggregation. Clinical trials have demonstrated efficacy of these drugs to reduce ischemic complications after percutaneous coronary interventions. In the setting of acute coronary syndromes without persistent ST segment elevation, abciximab improves outcomes in case of revascularization. Tirofiban and eptifibatide limit ischemic complications in the same setting, with additional effect in patients undergoing angioplasty. Blockers of the GPIIb/IIIa receptors should be the standard of care of patients with acute coronary syndromes. The optimal therapeutic strategy should include, after proper risk stratification, an early medical approach combined with an early revascularization.

Gene Therapy for Coronary Restenosis: A Promising Strategy for the New Millennium?

Gene therapy is an attractive alternative for reducing restenosis after percutaneous coronary interventions. Several approaches, using genes encoding antiproliferative, antimigratory, cytostatic, or cytotoxic proteins have been successfully tested in relevant animal models. Antiproliferative, gene-based strategies also appear to be good candidates for the highly proliferative lesion responsible for in-stent restenosis. However, several key issues, including vector safety and delivery mechanisms, still have to be resolved before percutaneous gene therapy can be widely applied in the clinic. The amount of experimental research in this field indicates a medical evolution that can (and should) not be ignored by cardiologists.

Percutaneous gene therapy using recombinant adenoviruses encoding human herpes simplex virus thymidine kinase, human PAI-1, and human NOS3 in balloon-injured porcine coronary arteries.

Local intracoronary delivery of recombinant adenoviruses expressing anti-migratory or anti-proliferative proteins including human constitutive endothelial nitric oxide synthase (NOS3), plasminogen activator inhibitor 1 (PAI-1), or herpesvirus thymidine kinase (TK) (combined with ganciclovir) was used to prevent neointimal formation in porcine coronary arteries. After balloon injury of the left anterior descending (LAD) coronary artery, animals received an intramural injection of adenovirus (1.5 X 10(9) PFU) carrying either the NOS3 cDNA (AdCMVNOS3, n = 12), the PAI-1 cDNA (AdCMVPAI-1, n = 12), the TK cDNA (AdMLPItk, n = 12), or no cDNA (AdpL+, n = 12). After 28 days, morphometric analysis was performed on coronary sections from all segments demonstrating injury. The internal elastic lamina (IEL) fracture length normalized to the IEL perimeter (initial injury) and the neointimal area normalized to the vessel area (response to injury) were used to generate linear regression lines and calculate an index of stenosis for the respective treatment groups. The response to injury was significantly smaller in AdCMVNOS3- and AdMLPItk-infected animals than in AdpL+-infected animals (slopes = 0.86 +/- 0.05 and 0.69 +/- 0.07 versus 1.11 +/- 0.06, p < 0.005 and p < 0.0001, respectively) but not in AdCMVPAI-1-infected animals (slope = 1.26 +/- 0.04, p = 0.04). No viral shedding was observed and there was no acute systemic toxicity after gene transfer. An increase in neutralizing antibody titers against Ad vectors was observed without any detectable response to the transgene products (NOS3, PAI-1). Local gene transfer of NOS3 and TK may hold promise as a safe and effective adjunctive treatment to reduce neointimal formation after percutaneous coronary intervention in humans.

[Anomalous origin of coronary arteries from three separate ostia in the right sinus of valsalva. A case port and review of the literature]. / Naissance anormale des coronaires à partir de trois ostiums séparés dans le sinus antéro-droit. A propos d'un cas et revue de la littérature.

The authors report the case of a patient undergoing coronary angiography for a lateral myocardial infarction related with atherosclerosic lesions but associated with a rare anomalous origin of all three coronary arteries from separate ostia in the right sinus of Valsalva. Anomalous origin of coronary arteries from the opposite sinus are potentially serious especially among young subjects and when a vessel runs between the aorta and pulmonary artery. Clinical presentation, angiographic diagnostic and treatment strategies are discussed.

Percutaneous adenoviral gene transfer into porcine coronary arteries: is catheter-based gene delivery adapted to coronary circulation?

Recombinant adenoviral (Ad) vectors represent an efficient gene transfer system for targeting the cardiovascular system. Phenotypic modulation of coronary vascular cells in vivo is, however, critically dependent on the efficacy of local delivery devices. Four local drug delivery catheters were tested for intracoronary gene transfer efficiency: the Infiltrator (INF, n = 10), the Crescendo (CRE, n = 10), the Infusasleeve (SLE, n = 8), and the Remedy balloon (channel balloon [CHA], n = 8). After balloon injury of the LAD, Ad vector containing the firefly luciferase cDNA (AdCMVluc, 1.5 x 10(10) plaque-forming units) was administered at the site of injury. On day 4, tissue samples from different regions in the heart and from the liver were assayed for luciferase activity to evaluate local and systemic gene transfer. INF, CRE, and SLE catheters showed higher transduction levels of the target LAD segment than did the CHA catheter (median luciferase activity = 4.2 x 10(6), 11 x 10(6), and 1.3 x 10(6) light units [LU]/vessel versus 0.09 x 10(6) LU/vessel, respectively, p < 0.05). Luciferase activity was occasionally observed in nontarget tissues (right and left ventricular free wall, distal LAD, and liver) and was not significantly different between groups. The viral circulatory half-life was similar for the four groups (<1 min). Gene transfer efficiency was positively correlated with the degree of injury for the intralumenal catheters (CRE, SLE, and CHA) but was independent of the vessel wall injury for the intramural INF. Local drug delivery catheters enable efficient vascular gene transfer in balloon-injured coronary arteries, a prerequisite for further development of intracoronary gene therapy for restenosis.

Gene therapy in the cardiovascular system: an update.

This update reviews the remarkable progression in several cardiovascular gene transfer domains. The first chemical gene therapy protocols to stimulate angiogenesis in ischemic myocardium are discussed and both the great expectations as well as remaining hurdle are highlighted. In experimental models of restenosis and heart failure gene therapy shows promising results. Important question regarding vector-related limitations and suboptimal in vivo delivery systems will require expeditious attention for gene therapy to become a more widely applicable option in cardiovascular diseases.

Local adenovirus-mediated transfer of human endothelial nitric oxide synthase reduces luminal narrowing after coronary angioplasty in pigs.

BACKGROUND: Nitric oxide, synthesized from L-arginine by nitric oxide synthase (NOS), is a vasodilator and inhibits vascular smooth muscle cell (SMC) proliferation and migration. The effects of local NOS gene transfer on restenosis after experimental balloon angioplasty were investigated. METHODS AND RESULTS: Left anterior descending coronary artery angioplasty was performed in 25 pigs. Animals received an intramural injection of adenovirus (1.5 x 10(9) pfu) carrying either the NOS cDNA (AdCMVceNOS) or no cDNA (AdRR5) via the Infiltrator. Local gene transfer efficiency and bioactivity of recombinant protein were assessed after 4 days. Indices of restenosis were evaluated by computerized planimetry on coronary artery sections prepared 28 days after angioplasty. Adenoviral vectors permitted efficient gene delivery to medial SMCs and adventitial cells of coronary arteries. Vascular cGMP levels were depressed after angioplasty from 1.30+/-0.42 to 0.33+/-0.20 pmol/mg protein (P<0.05) but were restored after constitutive endothelial (ce) NOS gene transfer to 1.82+/-0.98 pmol/mg (P<0.05 versus injured group and P=NS versus control). The ratio of the neointimal area to the internal elastic lamina fracture length, maximal neointimal thickness, and percent stenosis were all reduced in AdCMVceNOS- versus AdRR5-transduced pigs (0.59+/-0.14 versus 0.80+/-0.19 mm, P=0.02; 0.75+/-0.21 versus 1.04+/-0.25 mm, P=0.019; and 53+/-15% versus 75+/-11%, P=0.006, respectively). Lumen area was significantly larger (0.70+/-0.35 mm2 in AdCMVceNOS versus 0.32+/-0.18 mm2 in AdRR5, P=0.007). CONCLUSIONS: Percutaneous adenovirus-mediated NOS gene transfer resulted in efficient local overexpression of functional NOS after angioplasty in coronary arteries. Restored NO production in injured coronary arteries significantly reduced luminal narrowing, most likely through a combined effect on neointima formation and on vessel remodeling after angioplasty.