Predictive Value of the Residual SYNTAX Score in Patients With Cardiogenic Shock.

BACKGROUND: In hemodynamically stable patients, complete revascularization (CR) following percutaneous coronary intervention (PCI) is associated with a better prognosis in chronic and acute coronary syndromes. OBJECTIVES: This study sought to assess the extent, severity, and prognostic value of remaining coronary stenoses following PCI, by using the residual SYNTAX score (rSS), in patients with cardiogenic shock (CS) related to myocardial infarction (MI). METHODS: The CULPRIT-SHOCK (Culprit Lesion Only Percutaneous Coronary Intervention [PCI] Versus Multivessel PCI in Cardiogenic Shock) trial compared a multivessel PCI (MV-PCI) strategy with a culprit lesion-only PCI (CLO-PCI) strategy in patients with multivessel coronary artery disease who presented with MI-related CS. The rSS was assessed by a central core laboratory. The study group was divided in 4 subgroups according to tertiles of rSS of the participants, thereby isolating patients with an rSS of 0 (CR). The predictive value of rSS for the 30-day primary endpoint (mortality or severe renal failure) and for 30-day and 1-year mortality was assessed using multivariate logistic regression. RESULTS: Among the 587 patients with an rSS available, the median rSS was 9.0 (interquartile range: 3.0 to 17.0); 102 (17.4%), 100 (17.0%), 196 (33.4%), and 189 (32.2%) patients had rSS = 0, 0 < rSS ≤5, 5 < rSS ≤14, and rSS >14, respectively. CR was achieved in 75 (25.2%; 95% confidence interval [CI]: 20.3% to 30.5%) and 27 (9.3%; 95% CI: 6.2% to 13.3%) of patients treated using the MV-PCI and CLO-PCI strategies, respectively. After multiple adjustments, rSS was independently associated with 30-day mortality (adjusted odds ratio per 10 units: 1.49; 95% CI: 1.11 to 2.01) and 1-year mortality (adjusted odds ratio per 10 units: 1.52; 95% CI: 1.11 to 2.07). CONCLUSIONS: Among patients with multivessel disease and MI-related CS, CR is achieved only in one-fourth of the patients treated using an MV-PCI strategy. and the residual SYNTAX score is independently associated with early and late mortality.

Contrast-induced acute kidney injury and mortality in ST elevation myocardial infarction treated with primary percutaneous coronary intervention.

OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is a common and potentially severe complication in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). There is no consensus on the best definition of CI-AKI to identify patients at risk of haemodialysis or death. The objective of this study was to assess the association of CI-AKI, using four definitions, on inhospital mortality, mortality or haemodialysis requirement over 1-year follow-up, in patients with STEMI treated with pPCI. METHODS: In this prospective, observational study, all patients with STEMI referred for pPCI were included. We identified independent variables associated with CI-AKI and mortality. RESULTS: We included 1114 consecutive patients with STEMI treated by pPCI. CI-AKI occurred in 18.3%, 12.2%, 15.6% and 10.5% of patients according to the CIN, Acute Kidney Injury Network (AKIN), Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) Modification of Diet in Renal Disease (MDRD) and RIFLE Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) definitions, respectively. The RIFLE (CKD-EPI) definition was the most discriminant definition to identify patients at higher risk of inhospital mortality (27.1% vs 4.0%; adjusted OR 2.7 (95% CI 1.4 to 5.1), p=0.003), 1-year mortality (27.4% vs 6.6%; adjusted OR 2.8 (95% CI 1.5 to 5.3), p=0.002) and haemodialysis requirement at 1-year follow-up (15.6% vs 2.7%; adjusted OR 6.7 (95% CI 3.3 to 13.6), p=0.001). Haemodynamic instability, cardiac arrest, preexisting renal failure, elderly age and a high contrast media volume were independently associated with 1-year mortality. Of interest, contrast-media volume was not correlated to increase of creatininaemia (r=0.06) or decrease in estimated glomerular filtration rate (r=0.05) after percutaneous coronary intervention in our population. CONCLUSIONS: CI-AKI is a frequent and serious complication of STEMI treated by pPCI. The RIFLE definition is the most accurate definition to identify patients with CI-AKI at high risk of mortality or haemodialysis.

Thrombus composition in sudden cardiac death from acute myocardial infarction.

BACKGROUND AND AIM: It was hypothesized that the pattern of coronary occlusion (thrombus composition) might contribute to the onset of ventricular arrhythmia and sudden cardiac death (SCD) in myocardial infarction (MI). METHODS: The TIDE (Thrombus and Inflammation in sudden DEath) study included patients with angiographically-proven acute coronary occlusion as the cause of a ST elevation MI (STEMI) complicated by Sudden Cardiac Death (SCD group) or not (STEMI group). Thrombi were obtained by thrombo-aspiration before primary percutaneous coronary stenting and analyzed with a quantitative method using scanning electron microscopy. We compared the composition of the thrombi responsible for the coronary occlusion between the two groups and evaluated factors influencing its composition. RESULTS: We included 121 patients and found that thrombus composition was not different between the SCD group (n=23) and the STEMI group (n=98) regarding content of fibrin fibers (60.3±18.4% vs. 62.4±18.4% respectively, p=0.68), platelets (16.3±19.2% vs. 15.616.7±%, p=0.76), erythrocytes (14.6±12.5% vs. 13±12.1%, p=0.73) and leukocytes (0.6±0.9% vs. 0.8±1.5%, p=0.93). Thrombus composition did not differ between patients receiving upstream-use of glycoprotein IIb/IIIa platelet receptor inhibitors (GPI) and patients free of GPI. The only factor found to influence thrombus composition was the ischemic time from symptom onset to primary PCI, with a decreased content in fibrin fibers (57.8±18.5% vs. 71.9±10.1%, p=0.0008) and a higher platelet content (19.2±19.1% vs. 7.9±5.7% p=0.014) in early presenters (<3h of ischemic time) vs. late presenters (>6h of ischemic time). CONCLUSION: Composition of intracoronary thrombi in STEMI patients does not differ between those presenting with and without SCD. Time from symptom onset to coronary reperfusion seems to be the strongest factor influencing thrombus composition in MI.

Angiopoietin-like 4 serum levels on admission for acute myocardial infarction are associated with no-reflow.

BACKGROUND: No-reflow in ST-segment elevation acute myocardial infarction (STEMI) is associated with a poor clinical prognosis. Its pathophysiological mechanisms are not fully elucidated yet but enhanced vascular permeability plays a key role in this phenomenon. Angiopoietin-like 4 (ANGPTL4) has been implicated in vascular permeability in experimental models of acute myocardial infarction (AMI). We therefore sought to investigate whether baseline ANGPTL4 serum levels are associated with no-reflow after primary percutaneous coronary intervention (PPCI). METHODS: We studied a group of 41 patients presenting with a first STEMI within 12h of onset of symptoms and who underwent successful PPCI. Blood samples were obtained from all patients on admission before the start of the procedure, for ANGPTL4 level measurement. No-reflow was assessed by cardiac magnetic resonance imaging (MRI), the reference method. RESULTS: MRI-detected no-reflow was observed in 20 patients (48.8%). Variables independently associated with no-reflow on multivariate logistic regression analysis were: lower ANGPTL4 serum levels (odds ratio 0.82, 95% CI 0.70-0.98, P=0.02), higher troponin T peak (odds ratio 1.03, 95% CI 1.00-1.05, P=0.03), higher incidence of left anterior descending coronary artery (LAD) as culprit artery (odds ratio 14.61, 95% CI 1.24-172.49, P=0.03), and higher C-reactive protein levels (odds ratio 1.18, 95% CI 1.00-1.39, P=0.05). CONCLUSION: ANGPTL4 serum levels predict MRI-detected no-reflow after successful PPCI in STEMI patients. Given the recently demonstrated therapeutic role of ANGPTL4 in diminishing no-reflow and limiting infarct size in pre-clinical animal models, these findings in humans may open up new possibilities in the field of research.

Heparin or enoxaparin anticoagulation for primary percutaneous coronary intervention.

OBJECTIVES: The aim of this study was to compare efficacy and safety outcomes among patients receiving enoxaparin or unfractionated heparin (UFH) while undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Primary PCI (pPCI) for ST elevation has traditionally been supported by UFH. The low molecular weight heparin enoxaparin may provide better outcomes when used for pPCI. METHODS: Consecutive eligible patients (580) undergoing pPCI enrolled in the prospective electronic Pitié-Salpêtrière registry of ischemic coronary syndromes (e-PARIS) registry were grouped according to whether they received UFH or enoxaparin as the sole anticoagulant. Logistic regression modeling, propensity-weighted adjustment, and sensitivity analyses were used to evaluate efficacy and safety endpoints for enoxaparin vs. UFH. RESULTS: Enoxaparin was administered to 346 patients and UFH to 234 without ACT or anti-Xa guided dose adjustment. PCI was performed through the radial artery in 90%, with frequent (75%) use of GPIIb/IIIa antagonists. Patients receiving enoxaparin were more likely to be therapeutically anticoagulated during the procedure (68% vs. 50%, P < 0.0001) and were less likely to experience death or recurrent myocardial infarction (MI) in hospital (adjusted OR 0.28 95% CI (0.12-0.68) or by 30 days (adjusted OR 0.35 95% CI 0.16-0.81). All cause mortality was also reduced in hospital (adjusted OR 0.32, 95% CI (0.12-0.85) and to 30 days (adjusted OR 0.40 95% CI 0.17-0.99). Other ischemic endpoints were similarly reduced with enoxaparin. Thrombolysis in myocardial infarction (TIMI) major bleeding events were numerically fewer among patients receiving enoxaparin (1.2% vs. 2.6%, P = 0.2). CONCLUSIONS: In patients with STEMI presenting for PCI, enoxaparin was associated with a reduction in all ischemic complications, more frequent therapeutic anticoagulation, and no increase in major bleeding when compared against unfractionated heparin. © 2010 Wiley-Liss, Inc.

Dose effect of clopidogrel reloading in patients already on 75-mg maintenance dose: the Reload with Clopidogrel Before Coronary Angioplasty in Subjects Treated Long Term with Dual Antiplatelet Therapy (RELOAD) study.

BACKGROUND: Clopidogrel loading has mostly been studied in clopidogrel-naïve patients. Whether clopidogrel-treated patients readmitted for an acute coronary syndrome or percutaneous coronary intervention can benefit from a new load of clopidogrel and at what dose remain unknown. Our aim was to evaluate the impact of 3 different strategies of administration of a loading dose of 900 mg clopidogrel in patients already treated with a maintenance dose of 75 mg clopidogrel for at least 7 days on residual platelet aggregation. METHODS AND RESULTS: Patients treated long term by clopidogrel 75 mg/d were assigned to receive a first loading dose of 300, 600, or 900 mg clopidogrel and 4 hours later a second loading dose of 600, 300, or 0 mg, respectively, to achieve a total loading dose of 900 mg in all patients. Platelet aggregation was evaluated at baseline, at 4 hours after the initial load (and before second load), and at 24 hours using light transmission aggregometry with 20 micromol ADP and the point-of-care assay VerifyNow P2Y(12). The primary objective of the study was to evaluate the inhibition (relative change) of residual platelet aggregation (percentage of IRPA) between 600- and 900-mg first loading at 4 hours. IRPA at 24 hours also was evaluated as a secondary objective, as well as the rate of suboptimal response at 4 hours defined as IRPA <10%. We included 166 consecutive patients with acute coronary syndromes (n=80, 48%) or stable coronary artery disease (n=86, 52%). Baseline characteristics were similar in the 3 dose groups. A significant stepwise increase was found in percentage IRPA assessed at 4 hours in patients initially assigned to 300 versus 600 versus 900 mg (30.7% versus 40.3% versus 64.0%, respectively; P=0.0024). The difference in percentage IRPA at 4 hours was not significant between 300 and 600 mg but was significant between 600 and 900 mg and between 300 and 900 mg. Percentage IRPA assessed at 24 hours when all patients had received 900 mg did not differ between the 3 loading regimens. The rates of suboptimal response (IRPA <10% at 4 hours) were 23.6%, 20.4%, and 5.3% with 300, 600, and 900 mg, respectively (P=0.02 for all). CONCLUSIONS: In patients treated long term with 75 mg clopidogrel, a new loading dose of 900 mg improves IRPA and reduces poor and/or slow response to clopidogrel significantly more than that obtained with 300 or 600 mg.

High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction.

BACKGROUND: Aldosterone, the final mediator of the renin-angiotensin-aldosterone pathway, is at its highest plasma levels at presentation for ST-elevation myocardial infarction (STEMI). Whether aldosterone level at presentation for STEMI is associated with adverse outcome remains unknown. METHODS AND RESULTS: Plasma aldosterone levels were measured at presentation in consecutive patients referred for primary percutaneous coronary intervention for STEMI. We assessed the association between aldosterone levels and in-hospital events and mortality during a 6-month follow-up. Of 356 STEMI patients, 23 and 36 died during the hospital stay and 6-month follow-up period, respectively. Nine other patients survived in-hospital cardiac arrest. High aldosterone levels were associated with an almost stepwise increase in rates of in-hospital death (P=0.01), cardiovascular death (P=0.03), heart failure (P=0.005), ventricular fibrillation (P=0.02), and resuscitated cardiac arrest (P=0.01). After adjustment for age, Killip class, and reperfusion status, compared with patients in the first aldosterone quartile group, those in the highest quartile were at higher risk of death (hazard ratio 3.28, 95% CI 1.09 to 9.89, P=0.035) and death or resuscitated cardiac arrest (hazard ratio 3.74, 95% CI 1.40 to 9.98, P=0.008) during the follow-up. CONCLUSIONS: Plasma aldosterone levels on admission among patients referred for primary percutaneous coronary intervention for STEMI are associated with early and late adverse clinical outcomes, including mortality. The association between high aldosterone levels and late mortality is independent of age, heart failure, and reperfusion status. Such results underline the pivotal role of aldosterone and justify a randomized trial to assess the early administration of aldosterone antagonists in the setting of STEMI.

Enoxaparin in unstable angina patients who would have been excluded from randomized pivotal trials.

OBJECTIVES: In the present study, we describe the characteristics and examine the anticoagulation levels and safety of subcutaneous enoxaparin in unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) patients who would not have been eligible in the Efficacy Safety Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis In Myocardial Infarction (TIMI)-11B trials. BACKGROUND: It is not known whether the benefit shown with enoxaparin in the selected population of pivotal trials can be extended to the real world. METHODS: In our center, all patients with UA/NSTEMI are anticoagulated with subcutaneous enoxaparin adjusted to creatinine clearance. Among 515 consecutive patients, we identified 174 who would not have been eligible for ESSENCE or TIMI-11B ("EP" group for excluded patients). We evaluated cardiovascular death or non-fatal myocardial infarction (MI), as well as major and minor bleeding events, at 30 days in the EP group and in patients without any of the exclusion criteria ("NEP" group for non-excluded patients). RESULTS: This EP group was older, had a higher female/male ratio, and more frequently had a history of MI or a diagnosis of non-Q MI on admission than the NEP group. The distribution of the anti-Xa activity was similar in both groups. The bleeding rates (major and minor) at 30 days were similar in the EP and NEP groups (2.3% vs. 2.9%, respectively, P = NS). On multivariate analysis, the use of glycoprotein IIb/IIIa inhibitors and the presence of hypertension were the only independent predictors of bleeding found in the whole population. Compared with the NEP group, the EP group had a fourfold increased rate of death or MI at 30 days (15.5% vs. 4.1%, p < 0.01). On multivariate analysis, the independent predictors of death or MI at 30 days were NSTEMI on admission, creatinine clearance, and heart failure. CONCLUSIONS: Patients who do not fit the enrollment criteria of ESSENCE/TIMI-11B have higher risk baseline characteristics for both bleeding and ischemic events. In these patients, enoxaparin with dose adjustment to creatinine clearance provides adequate anti-Xa levels and no excess of bleeding.