Dramatic effect of early clopidogrel administration in reducing mortality and MACE rates in ACS patients. Data from the Swiss registry AMIS-Plus.

BACKGROUND: Patients who have acute coronary syndromes with or without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy of early clopidogrel administration (300 mg) (<24 hours) when given with aspirin in such patients. METHODS: We included 30,243 patients who had an acute coronary syndrome with or without ST segment elevation. Data on early clopidogrel administration were available for 24,463 (81%). Some 15,525 (51%) of the total cohort were administrated clopidogrel within 24h of admission. RESULTS: In-hospital death occurred in 2.9% of the patients in the early clopidogrel group treated with primary PCI and in 11.4% of the patients in the other group without primary percutaneous coronary intervention (PCI) and no early clopidogrel. The unadjusted clopidogrel odds ratio (OR) for mortality was 0.31 (95% confidence interval 0.27-0.34; p <0.001). Incidence of major adverse cardiac death (MACE) was 4.1% in the early clopidogrel group treated with 1°PCI and 13.5% in the other group without primary PCI and no early clopidogrel (OR 0.35, confidence interval 0.32-0.39, p <0.001). Early clopidogrel administration and PCI were the only treatment lowering mortality as shown by mutlivariate analysis. CONCLUSIONS: The early administration of the anti-platelet agent clopidogrel in patients with acute coronary syndromes with or without ST-segment elevation has a beneficial effect on mortality and major adverse cardiac events. The lower mortality rate and incidence of MACE emerged with a combination of primary PCI and early clopidogrel administration.

New universal definition of myocardial infarction applicable after complex percutaneous coronary interventions?

OBJECTIVES: This study aimed to characterize myocardial infarction after percutaneous coronary intervention (PCI) based on cardiac marker elevation as recommended by the new universal definition and on the detection of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR). It is also assessed whether baseline inflammatory biomarkers are higher in patients developing myocardial injury. BACKGROUND: Cardiovascular magnetic resonance accurately assesses infarct size. Baseline C-reactive protein (CRP) and neopterin predict prognosis after stent implantation. METHODS: Consecutive patients with baseline troponin (Tn) I within normal limits and no LGE in the target vessel underwent baseline and post-PCI CMR. The Tn-I was measured until 24 h after PCI. Serum high-sensitivity CRP and neopterin were assessed before coronary angiography. RESULTS: Of 45 patients, 64 (53 to 72) years of age, 33% developed LGE with infarct size of 0.83 g (interquartile range: 0.32 to 1.30 g). A Tn-I elevation >99% upper reference limit (i.e., myocardial necrosis) (median Tn-I: 0.51 μg/l, interquartile range: 0.16 to 1.23) and Tn-I > 3× upper reference limit (i.e., type 4a myocardial infarction [MI]) occurred in 58% and 47% patients, respectively. LGE was undetectable in 42% and 43% of patients with periprocedural myocardial necrosis and type 4a MI, respectively. Agreement between LGE and type 4a MI was moderate (kappa = 0.45). The levels of CRP or neopterin did not significantly differ between patients with or without myocardial injury, detected by CMR or according to the new definition (p = NS). CONCLUSIONS: This study reports the lack of substantial agreement between the new universal definition and CMR for the diagnosis of small-size periprocedural myocardial damage after complex PCI. Baseline levels of CRP or neopterin were not predictive for the development of periprocedural myocardial damage.

Influence of socioeconomic factors on delays, management and boutcome amongst patients with acute myocardial infarction undergoing primary percutaneous coronary intervention

Background¦The outcome after primary percutaneous coronary intervention (pPCI) for STElevation¦Myocardial Infarction (STEMI) is strongly affected by time delays. In thepresent study, we sought to identify the impact of specific socioeconomic factors on time delays, subsequent STEMI management and outcomes in STEMI patients from a well-defined region of the French part of Switzerland.¦Method¦A total of 402 consecutive patients undergoing pPCI for STEMI in a large tertiary hospital were retrospectively studied. Symptom-to-first-medical-contact time was analyzed for the following socioeconomic factors: level of education, gender, origin and marital status. Main exclusion criteria were: time delay beyond 12 hours, previous treatment by fibrinolysis or patients immediately referred for CABG.¦Therefore, 352 patients were finally included.¦Results¦At one year, there was no difference in mortality amongst the different socioeconomic groups. Furthermore, there was no difference in management characteristics between them. Symptom-to-first-medical-contact time was significantly higher for patients with a low level of education, Swiss citizens and non-married patients with median differences of 40 minutes, 48 minutes, and 60 minutes, respectively (p<0.05).¦Nevertheless, no difference was found regarding in-hospital management and clinical outcome.¦Conclusion¦This study demonstrates that symptom-to-first-medical-contact time is higher amongst people with a lower educational level, Swiss-citizens, and non-married people. Because of the low mortality rate in general, these differences in time delays did not affect clinical outcomes. Still, primary prevention measures should particularly focus on these vulnerable populations.

Fatal myocardial infarction after lung resection in a patient with prophylactic preoperative coronary stenting.

In this report we present the case of a 77-yr-old man who underwent resection of the upper lobe of the left lung for a carcinoma, six weeks after percutaneous transluminal coronary angioplasty (PTCA) with stenting of the left anterior descending (LAD) and circumflex coronary arteries. Antiplatelet therapy with clopidogrel was interrupted two weeks before surgery to allow for epidural catheter placement and to minimize haemorrhage. The surgical procedure was uneventful. In the immediate postoperative period, however, the patient suffered severe myocardial ischaemia. Emergency coronary angiography showed complete thrombotic occlusion of the LAD stent. In spite of successful recanalization, reinfarction occurred and the patient died in cardiogenic shock. Prophylactic preoperative coronary stenting may put the patient at risk of stent thrombosis if surgery cannot be postponed for three months. In such cases, other strategies such as perioperative beta-blockade for preoperative cardiac management should be considered.

Reduced ejection fraction after myocardial infarction: is it sufficient to justify implantation of a defibrillator?

BACKGROUND: Improved survival after prophylactic implantation of a defibrillator in patients with reduced left ventricular ejection fraction (EF) after myocardial infarction (MI) has been demonstrated in patients who experienced remote MIs in the 1990s. The absolute survival benefit conferred by this recommended strategy must be related to the current risk of arrhythmic death, which is evolving. This study evaluates the mortality rate in survivors of MI with impaired left ventricular function and its relation to pre-hospital discharge baseline characteristics. METHODS: The clinical records of patients who had sustained an acute MI between 1999 and 2000 and had been discharged from the hospital with an EF of < or = 40% were included. Baseline characteristics, drug prescriptions, and invasive procedures were recorded. Bivariate and multivariate analyses were performed using a primary end point of total mortality. RESULTS: One hundred sixty-five patients were included. During a median follow-up period of 30 months (interquartile range, 22 to 36 months) 18 patients died. The 1-year and 2-year mortality rates were 6.7% and 8.6%, respectively. Variables reflecting coronary artery disease and its management (ie, prior MI, acute reperfusion, and complete revascularization) had a greater impact on mortality than variables reflecting mechanical dysfunction (ie, EF and Killip class). CONCLUSIONS: The mortality rate among survivors of MIs with reduced EF was substantially lower than that reported in the 1990s. The strong decrease in the arrhythmic risk implies a proportional increase in the number of patients needed to treat with a prophylactic defibrillator to prevent one adverse event. The risk of an event may even be sufficiently low to limit the detectable benefit of defibrillators in patients with the prognostic features identified in our study. This argues for additional risk stratification prior to the prophylactic implantation of a defibrillator.

A noninvasive diagnostic tool to differentiate myocarditis from myocardial infarction: late gadolinium enhanced cardiac magnetic resonance.

Studies in adults have shown that late gadolinium enhanced cardiac magnetic resonance is a safe and noninvasive diagnostic tool which allows one to differentiate myocardial infarction from myocarditis. We believe that it may also be highly useful in the paediatric population for the same purpose.

Comparison of results of intravenous infusion of anistreplase versus streptokinase in acute myocardial infarction.

This randomized study compares the coronary perfusion rate in patients with acute myocardial infarction (AMI) treated with 2 different intravenous thrombolytic agents: streptokinase 1.5 million U given over 60 minutes and anisoylated human plasminogen streptokinase activator complex (anistreplase) administrated as a bolus of 30 U over 5 minutes. One hundred seventy-five patients (149 men and 26 women, mean age 54 years) have been included in this study. Eighty-nine patients were treated with anistreplase and 86 patients with streptokinase. AMI was inferior in 54 patients (61%) in the anistreplase group and in 54 patients (63%) in the streptokinase group. It was anterior in 35 (40%) and 32 (37%) patients, respectively. Coronary angiography and ventriculography were performed at a mean time (+/- SEM) of 207 +/- 11 minutes after the beginning of thrombolysis in 170 patients. A perfusion score grade of 2 or 3 according to the Thrombolysis in Myocardial Infarction trial was found in 63 patients (72%) in the anistreplase group and in 56 patients (68%) in the streptokinase group (p = NS). Severe bleeding occurred in 7 patients (8%) after anistreplase and in 6 patients (7%) after streptokinase. No cerebral hemorrhage occurred. Nine patients (5%) died during their hospital stay: 6 after anistreplase and 3 after streptokinase. It is concluded that intravenous administration of anistreplase or streptokinase is efficient and safe. Coronary patency 207 minutes after fibrinolysis, incidence of adverse events and mortality are similar in both groups.

Cardiac rotation and relaxation after anterolateral myocardial infarction.

BACKGROUND: Both systolic and diastolic dysfunction have been observed in patients with anterolateral myocardial infarction. Diastolic dysfunction is related to disturbances in relaxation and diastolic filling. OBJECTIVE: To analyse cardiac rotation, regional shortening and diastolic relaxation in patients with anterolateral infarction. METHODS: Cardiac rotation and relaxation in controls and patients with chronic anterolateral infarction were assessed by myocardial tagging. Myocardial tagging is based on magnetic resonance imaging and allows us to label specific myocardial regions for imaging cardiac motion (rotation, translation and radial displacement). A rectangular grid was placed on the myocardium (basal, equatorial and apical short-axis plane) of each of 18 patients with chronic anterolateral infarction and 13 controls. Cardiac rotation, change in area and shortening of circumference were determined in each case. RESULTS: The left ventricle in controls performs a systolic wringing motion with a clockwise rotation at the base and a counterclockwise rotation at the apex when viewed from the apex. During relaxation a rotational motion in the opposite direction (namely untwisting) can be observed. In patients with anterolateral infarction, there is less systolic rotation at the apex and diastolic untwisting is delayed and prolonged in comparison with controls. In the presence of a left ventricular aneurysm (n = 4) apical rotation is completely lost. There is less shortening of circumference in infarcted and remote regions. CONCLUSIONS: The wringing motion of the myocardium might be an important mechanism involved in maintaining normal cardiac function with minimal expenditure of energy. This mechanism no longer operates in patients with left ventricular aneurysms and operates significantly less than normal in those with anterolateral hypokinaesia. Diastolic untwisting is significantly delayed and prolonged in patients with anterolateral infarction, which could explain the occurrence of diastolic dysfunction in these patients.

Cutting edge: IL-1α is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction.

Myocardial infarction (MI) induces a sterile inflammatory response that contributes to adverse cardiac remodeling. The initiating mechanisms of this response remain incompletely defined. We found that necrotic cardiomyocytes released a heat-labile proinflammatory signal activating MAPKs and NF-κB in cardiac fibroblasts, with secondary production of cytokines. This response was abolished in Myd88(-/-) fibroblasts but was unaffected in nlrp3-deficient fibroblasts. Despite MyD88 dependency, the response was TLR independent, as explored in TLR reporter cells, pointing to a contribution of the IL-1 pathway. Indeed, necrotic cardiomyocytes released IL-1α, but not IL-1β, and the immune activation of cardiac fibroblasts was abrogated by an IL-1R antagonist and an IL-1α-blocking Ab. Moreover, immune responses triggered by necrotic Il1a(-/-) cardiomyocytes were markedly reduced. In vivo, mice exposed to MI released IL-1α in the plasma, and postischemic inflammation was attenuated in Il1a(-/-) mice. Thus, our findings identify IL-1α as a crucial early danger signal triggering post-MI inflammation.

A CMR study of the effects of tissue edema and necrosis on left ventricular dyssynchrony in acute myocardial infarction: implications for cardiac resynchronization therapy.

ABSTRACT: BACKGROUND: In acute myocardial infarction (AMI), both tissue necrosis and edema are present and both might be implicated in the development of intraventricular dyssynchrony. However, their relative contribution to transient dyssynchrony is not known. Cardiovascular magnetic resonance (CMR) can detect necrosis and edema with high spatial resolution and it can quantify dyssynchrony by tagging techniques. METHODS: Patients with a first AMI underwent percutaneous coronary interventions (PCI) of the infarct-related artery within 24 h of onset of chest pain. Within 5-7 days after the event and at 4 months, CMR was performed. The CMR protocol included the evaluation of intraventricular dyssynchrony by applying a novel 3D-tagging sequence to the left ventricle (LV) yielding the CURE index (circumferential uniformity ratio estimate; 1 = complete synchrony). On T2-weighted images, edema was measured as high-signal (>2 SD above remote tissue) along the LV mid-myocardial circumference on 3 short-axis images (% of circumference corresponding to the area-at-risk). In analogy, on late-gadolinium enhancement (LGE) images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. Necrosis was also quantified on LGE images covering the entire LV (expressed as %LV mass). Finally, salvaged myocardium was calculated as the area-at-risk minus necrosis (expressed as % of LV circumference). RESULTS: After successful PCI (n = 22, 2 female, mean age: 57 ± 12y), peak troponin T was 20 ± 36ug/l and the LV ejection fraction on CMR was 41 ± 8%. Necrosis mass was 30 ± 10% and CURE was 0.91 ± 0.05. Edema was measured as 58 ± 14% of the LV circumference. In the acute phase, the extent of edema correlated with dyssynchrony (r2 = -0.63, p < 0.01), while extent of necrosis showed borderline correlation (r2 = -0.19, p = 0.05). PCI resulted in salvaged myocardium of 27 ± 14%. LV dyssynchrony (=CURE) decreased at 4 months from 0.91 ± 0.05 to 0.94 ± 0.03 (p < 0.004, paired t-test). At 4 months, edema was absent and scar %LV slightly shrunk to 23.7 ± 10.0% (p < 0.002 vs baseline). Regression of LV dyssynchrony during the 4 months follow-up period was predicted by both, the extent of edema and its necrosis component in the acute phase. CONCLUSIONS: In the acute phase of infarction, LV dyssynchrony is closely related to the extent of edema, while necrosis is a poor predictor of acute LV dyssynchrony. Conversely, regression of intraventricular LV dyssynchrony during infarct healing is predicted by the extent of necrosis in the acute phase.

Usefulness of late enhancement MRI as diagnostic tool to differentiate myocardial infarction from myocarditis

Introduction: Residual pulmonary artery (PA) anomalies are a major concern after surgery for cono-truncal malformations. This study sought to assess residual PA anomalies using MRI/MRA. Methods: 43 MRI/MRA studies were performed in 37 patients after corrective surgery for cono-truncal malformations. MRI/MRA studies comprised spin-echo, cine, velocity-encoded and 3D Gadolinium-enhanced MRA sequences. Residual PA anomalies were searched in ail patients; angiographie data were available in 13 patients and a comparison with MRI/MRA was made. Results: 32/37 patients had postoperative anomalies of the pulmonary arterial tree. Left pulmonary artery stenosis was the most common finding (14/32), followed by stenosis at multiple sites (11/32). Isolated right pulmonary artery stenosis was rare (2/32). The median time interval between MRI/MRA and angiography in the 13 patients undergoing both types of studies was 54 days. The findings between the two examinations were identical regarding stenoses and collateral vessels. In 4 patients, the MRI/MRA study allowed to plan interventional catheterization with balloon dilatation and/or stenting of the obstructed arteries or co il-occlusion of systemic collaterals. Eleven patients had additional surgery based on MRI/MRA findings. Conclusions: Post-operative anomalies of the PA in cono-truncal malformations can reliably be detected with MRI/MRA. This technique allows planning of the intervention al or surgical procedure to correct the residual anomalies and may th us replace or precede catheterization during the follow-up of surgically corrected cono-truncal malformations.

Reduced ejection fraction after myocardial infarction: is it sufficient to justify implantation of a defibrillator ?

Introduction : La diminution de la fraction d'éjection après infarctus du myocarde est-elle suffisante pour justifier l'implantation prophylactique de défibrillateur ? Introduction: La diminution de la fraction d'éjection (FE) est un facteur prédictif majeur de mortalité cardiaque chez les patients avec ancien infarctus du myocarde (IM). Les plus récentes études, pour la plupart conduites à la fin des années 90, montrent une diminution de la mortalité post-hospitalière à 10 à 20% par année. Une amélioration de la survie par implantation prophylactique de défibrillateurs a été démontrée chez les patients avec dysfonction myocardique avancée après ancien IM dans la cadre de l'étude MADIT II (Multicenter Automatic Defibrillator Implantation Trial) et est depuis lors, considérée comme une thérapie recommandée. Le bénéfice de l'implantation prophylactique de défibrillateurs en terme de nombre nécessaire de patients à traiter pour prévenir un évènement est d'un intérêt primordial en raison des complications potentielles liées à la procédure et l'appareillage, des implications psychologiques ainsi qu'en raison de l'analyse coût-efficacité. Le nombre de patients à traiter est corrélé au risque actuel de mortalité rythmique, probablement influencé par les récentes avancées thérapeutiques dans la prise en charge aigue de l'IM (notamment par angioplastie primaire) et de l'insuffisance cardiaque. Or, dans '' l'étude MADIT II, le recrutement des patients était effectué entre 1997 et 2001 et l'intervalle moyen entre l'IM et le recrutement était de plus de 6 ans. Le but de l'étude était donc d'évaluer, dans la pratique générale, la mortalité actuelle de patients ayant survécu à un IM avec diminution consécutive significative de la FE. La stratification du risque sur la base des variables hospitalières a de même été explorée. Méthode: Une analyse de cohorte de patients avec infarctus aigu du myocarde admis de 1999 à 2000 a été effectuée dans 2 centres hospitaliers (un universitaire et un cantonal). Tous les dossiers cliniques des patients sortis d'hôpital avec FE documentée ≤ 0.40 ont été inclus. Les caractéristiques des patients, les procédures diagnostiques et thérapeutiques ainsi que la médication étaient reportées. La période de suivi débutait à la sortie d'hôpital. Les end-points primaires étaient la mortalité globale, la mortalité cardiaque et les morts subites. Une analyse bivariée et multivariée a été effectuée. Résultats: 165 patients ont été inclus. Durant un suivi médian de 30 mois (interquartile range 22-36), 18 patients sont décédés (5 morts classifiées comme cardiaques, 8 comme subites, 5 de causes non cardiaques). Les taux de mortalité à un et deux ans selon analyse de Kaplan-Meier étaient de 6.7 et 8.6%, respectivement. Les variables reflétant l'atteinte coronarienne et sa prise en charge (antécédent d'IM, reperfusion aigue, revascularisation complète) étaient plus significativement associées à la mortalité comparées aux variables reflétant la dysfonction myocardique (FE, classe Killip à l'admission). Conclusion : La mortalité des patients ayant survécu à un IM avec dysfonction myocardique avancée a diminué de façon substantielle depuis la fin des années 90. La diminution de la mortalité rythmique implique une augmentation proportionnelle du nombre de patients à traiter par implantation de défibrillateur pour prévenir un évènement. Par ailleurs, une stratification du risque après IM basée uniquement sur la FE semble être inappropriée au vu de son impact mineur sur la mortalité comparé aux autres facteurs de risque identifiés dans notre étude. Les patients sans antécédents d'infarctus et ceux ayant bénéficié d'une revascularisation aigue ou complète avait une mortalité cumulée à 2 ans de, respectivement, 2.5%, 3.9% et 2.3%. Pour ce type de patients à bas risque le bénéfice de l'implantation prophylactique de défibrillateur doit être remis en question. Au vu de cette étude, une stratification additionnelle du risque avant implantation de défibrillateur est à considérer.