Imanol Otaegui

Intracoronary injection of adenosine before reperfusion in patients with ST-segment elevation myocardial infarction: A randomized controlled clinical trial

BACKGROUND The effect of intracoronary adenosine (ADO) on ST-segment elevation myocardial infarction (STEMI) size and adverse remodeling is not well established. METHODS In a double-blind trial, 201 patients with STEMI were randomized to receive percutaneous coronary intervention (PCI) within 6 hours of symptom onset, 4.5mg ADO or saline immediately prior to reperfusion. Primary end-point: percentage of total myocardial necrotic mass by cardiac magnetic resonance (CMR) 2-7 days post-reperfusion. Secondary end-points: changes in left ventricular volumes and ejection fraction (LVEF) at baseline and at 6 months. RESULTS Baseline CMR could not be performed in 20 patients. Overall, no significant differences were observed between ADO and placebo regarding infarct size (20.8% vs. 22.5%; p=0.40). However, infarct size was significantly reduced (19.4% vs. 25.7%; p for interaction=0.031) in those with ischemia duration below the median (200 min). CMR at 6 months, performed in 138 patients, did not show statistically significant differences between groups in the rate of LVEF increase (3.3 units (SD 9.6) in ADO group vs. 1.5 units (SD 9) in placebo group; p=0.25). In the subgroup analysis, among patients with ischemia time below 200 min, the increase in LVEF was slightly higher with ADO (3.59% vs. 0.43%; p for interaction=0.06). CONCLUSIONS Although our study failed to demonstrate that intracoronary administration of ADO prior to PCI limits infarct size, in patients receiving early PCI ADO might enhance myocardial salvage and has a favorable effect on LVEF evolution, which may help to reconcile apparently contradictory results of previous studies. CLINICAL TRIAL REGISTRATION http://clinicaltrials.gov (NCT00781404).

Cuantificación del área miocárdica en riesgo: validación de puntuaciones angiográficas coronarias con métodos de resonancia magnética cardiovascular

INTRODUCTION AND OBJECTIVES Quantification of myocardial area-at-risk after acute myocardial infarction has major clinical implications and can be determined by cardiovascular magnetic resonance. The Bypass Angioplasty Revascularization Investigation Myocardial Jeopardy Index (BARI) and Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) angiographic scores have been widely used for rapid myocardial area-at-risk estimation but have not been directly validated. Our objective was to compare the myocardial area-at-risk estimated by BARI and APPROACH angiographic scores with those determined by cardiovascular magnetic resonance. METHODS In a prospective study, cardiovascular magnetic resonance was performed in 70 patients with a first successfully-reperfused ST-segment elevation acute myocardial infarction in the first week after percutaneous coronary intervention. Myocardial area-at-risk was obtained both by analysis of T2-short tau inversion recovery sequences and calculation of infarct endocardial surface area with late enhancement sequences. These results were compared with those of BARI and APPROACH scores. RESULTS BARI and APPROACH showed a statistically significant correlation with T2-short tau inversion recovery for myocardial area-at-risk estimation (BARI, intraclass correlation coefficient=0.72; P<.001; APPROACH, intraclass correlation coefficient=0.69; P<.001). Better correlations were observed for anterior acute myocardial infarction than for other locations (BARI, intraclass correlation coefficient=0.73 vs 0.63; APPROACH, intraclass correlation coefficient=0.68 vs 0.50). Infarct endocardial surface area showed a good correlation with both angiographic scores (BARI, intraclass correlation coefficient=0.72; P<.001; with APPROACH, intraclass correlation coefficient=0.70; P<.001). CONCLUSIONS BARI and APPROACH angiographic scores allow reliable estimation of myocardial area-at-risk in current clinical practice, particularly in anterior infarctions. Full English text available from:www.revespcardiol.org.

Increased von Willebrand factor, P-selectin and fibrin content in occlusive thrombus resistant to lytic therapy

Therapeutic fibrinolysis is ineffective in 40 % of ST-segment elevation acute myocardial infarction (STEMI) patients, but understanding of the mechanisms is incomplete. It was our aim to compare the composition of coronary thrombus in lysis-resistant STEMI patients with that of lysis-sensitive patients. Intracoronary thrombi (n=64) were obtained by aspiration in consecutive STEMI patients. Of them, 20 had received fibrinolysis and underwent rescue percutaneous coronary intervention (r-PCI, lysis-resistant patients) and 44 underwent primary PCI (p-PCI). Lysis-sensitivity was determined in vitro by clot permeability measurements and turbidimetric lysis in plasma of 44 patients undergoing p-PCI and 20 healthy donors. Clot-lysis sensitivity was defined as a clot-lysis time not greater than 1 SD over the mean of healthy donors. Coronary thrombus composition in 20 lysis-resistant and in 20 lysis-sensitive patients was analysed by immunofluorescence with confocal microscopy. Plasma biomarkers (P-selectin, VWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin and CD34+) were measured simultaneously on peripheral blood. Lysis-resistant clots had higher levels of fibrin (p=0.02), P-selectin (p=0.03) and VWF (p=0.01) than lysis-sensitive clots. Among thrombi obtained ≤ 6 hours after onset of symptoms, those from lysis-resistant patients showed a higher content in fibrin than those from p-PCI patients (p=0.01). Plasma PAI-1 (p=0.02) and D-dimer levels were significantly higher (p=0.003) in lysis-resistant patients, whereas plasmin levels were lower (p=0.03). Multivariate analysis showed the content of fibrin and VWF within thrombus as predictors of thrombolysis resistance. In conclusion, coronary thrombi in STEMI patients resistant to fibrinolysis are characterised by higher fibrin, P-selectin and VWF content than lysis-sensitive thrombi.

Everolimus-Eluting Stents in Patients With Bare-Metal and Drug-Eluting In-Stent Restenosis Results From a Patient-Level Pooled Analysis of the RIBS IV and V Trials

Background—Treatment of patients with drug-eluting stent (DES) in-stent restenosis (ISR) is more challenging than that of patients with bare-metal stent ISR. However, the results of everolimus-eluting stents (EES) in these distinct scenarios remain unsettled. Methods and Results—A pooled analysis of the RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent) and RIBS V (Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent) randomized trials was performed using patient-level data to compare the efficacy of EES in bare-metal stent ISR and DES-ISR. Inclusion and exclusion criteria were identical in both trials. Results of 94 patients treated with EES for bare-metal stent ISR were compared with those of 155 patients treated with EES for DES-ISR. Baseline characteristics were more adverse in patients with DES-ISR, although they presented later and more frequently with a focal pattern. After intervention, minimal lumen diameter (2.22±0.5 versus 2.38±0.5 mm, P=0.01) was smaller in the DES-ISR group. Late angiographic findings (89.3% of eligible patients), including minimal lumen diameter (2.03±0.7 versus 2.36±0.6 mm, P<0.001) and diameter stenosis (23±22 versus 13±17%, P<0.001) were poorer in patients with DES-ISR. Results were consistent in the in-segment and in-lesion analyses. On multiple linear regression analysis, minimal lumen diameter at follow-up remained significantly smaller in patients with DES-ISR. Finally, at 1-year clinical follow-up (100% of patients), mortality (2.6 versus 0%, P<0.01) and need for target vessel revascularization (8 versus 2%, P=0.03) were higher in the DES-ISR group. Conclusions—This patient-level pooled analysis of the RIBS IV and RIBS V randomized clinical trials suggests that EES provide favorable outcomes in patients with ISR. However, the results of EES are less satisfactory in patients with DES-ISR than in those with bare-metal stent ISR. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01239953 and NCT01239940.

Relation of ST-segment elevation before and after percutaneous transluminal coronary angioplasty to left ventricular area at risk, myocardial infarct size, and systolic function.

Electrocardiography is an excellent tool for decision making in patients with ST elevation myocardial infarction (STEMI). However, little is known on the correlation between its dynamic changes during primary percutaneous coronary intervention (PCI) and the anatomic information provided by cardiovascular magnetic resonance. The study aimed to assess the predictive value of dynamic ST-segment changes before and after PCI on myocardial area at risk (AAR), infarct size, and left ventricular function in patients with STEMI. Eighty-five consecutive patients with a first STEMI were included. An electrocardiogram was recorded before and after PCI at 1, 24, 48, 72, and 120 hours. Sum of ST elevation (sumSTE), the number of STE, and STE resolution (resSTE) were determined. Complete resSTE was defined as ≥70% resolution, and patients were classified into 3 groups: group 1 (resSTE 1 hour after PCI) n = 39; group 2 (resSTE 120 hour after PCI) n = 27; and group 3, without resSTE (n = 19). Cardiovascular magnetic resonance was performed during hospitalization and at 6 months. Left ventricular volumes, ejection fraction, AAR, infarct size, myocardial salvage index, and microvascular obstruction were determined. Before PCI, the number of STE and sumSTE were best associated with AAR (p <0.001). After PCI, lack of resSTE (group 3) was associated with larger infarct size, MVO, and lower myocardial salvage index. However, sumSTE at 120 hours after PCI best discriminated patients with larger infarct size, ventricular volumes, and lower ejection fraction during hospitalization and at follow-up. In conclusion, admission sumSTE best correlates with AAR, whereas sumSTE at 120 hours rather than early resSTE best correlates with infarct size and left ventricular volumes during hospitalization and at 6 months.

Prognostic impact of tissue factor pathway on long-term ischemic events of ST-elevated myocardial infarction treated with a primary percutaneous coronary intervention.

pacing in Becker muscular dystrophy as assessed by tissue Doppler imaging. Heart Lung 2005;34:317–20. [10] Finsterer J, Bittner RE, Grimm M. Cardiac involvement in Beckers muscular dystrophy, necessitating heart transplantation, 6 years before apparent skeletal muscle involvement. Neuromuscul Disord 1999;9:598–600. [11] Wu RS, Gupta S, Brown RN, et al. Clinical outcomes after cardiac transplantation in muscular dystrophy patients. J Heart Lung Transplant 2010;29:432–8. [12] Finsterer J, Stollberger C, Meng G. Progressive respiratory insufficiency in the absence of cardiac disease in late-stage duchenne muscular dystrophy. Respir Care Mar 2013;58:e28–30.

Acute Coronary SyndromesIMMUNOHISTOCHEMICAL AND MOLECULAR CHARACTERISTICS OF CORONARY THROMBUS RESISTANT TO FIBRINOLYSIS

The fibrinolysis is ineffective in 40p of patients with ST-segment elevation acute myocardial infarction (STEMI). The purpose of this study is to compare the content of thrombotic and fibrinolytic factors into the thrombus resistant to fibrinolysis, regarding to the thrombus sensible to lysis

Area at risk and collateral circulation in a first acute myocardial infarction with occluded culprit artery. STEMI vs non-STEMI patients

BACKGROUND It is unclear why among patients with first acute myocardial infarction and an occluded culprit artery only some present ST segment elevation. In fact, there is no study that compares the angiographic area at risk and the collateral circulation in first NSTEMI vs STEMI patients. METHODS AND RESULTS 205 patients admitted for myocardial infarction with occluded culprit artery were included, 132 STEMI and 73 NSTEMI. Demographic data, the area at risk determined by the BARI score and collateral supply by the Rentrop score from the 2 groups were compared. NSTEMI patients showed lower peak Tn I than STEMI in the overall group but also in the 3 subsets with different culprit arteries (p < .001). They also presented a higher rate of left circumflex coronary artery (CFX) as culprit artery (52% vs 14%, p < .001), smaller BARI score area of the culprit artery (5.4 vs 7.6, p < .001), and higher frequency of well-developed collaterals (Rentrop score ≥ 2, 1.82 vs 0.41, p < .001). The latter was also higher in each of the 3 different culprit arteries (p = .002-<0.001) Among 38 NSTEMI patients with CFX occlusion, 20 with ≥1 mm ST depression in V2 to V4 (possible posterior infarction) showed a similar Rentrop score than the 18 with other ECG changes but lower Tn I peak (p = .012). CONCLUSIONS In first acute myocardial infarction with an occluded culprit artery NSTEMI patients - including those with possible posterior infarction - present smaller infarct size and higher collateral blood supply than STEMI patients in each of the 3 main culprit arteries.

Genetic association study of coronary collateral circulation in patients with coronary artery disease using 22 single nucleotide polymorphisms corresponding to 10 genes involved in postischemic neovascularization

BackgroundCollateral growth in patients with coronary artery disease (CAD) is highly heterogeneous. Although multiple factors are thought to play a role in collateral development, the contribution of genetic factors to coronary collateral circulation (CCC) is largely unknown. The goal of this study was to assess whether functional single nucleotide polymorphisms (SNPs) in genes involved in vascular growth are associated with CCC.Methods677 consecutive CAD patients were enrolled in the study and their CCC was assessed by the Rentrop method. 22 SNPs corresponding to 10 genes involved in postischemic neovascularization were genotyped and multivariate logistic regression models were adjusted using clinically relevant variables to estimate odds ratios and used to examine associations of allelic variants, genotypes and haplotypes with CCC.ResultsStatistical analysis showed that the HIF1A rs11549465 and rs2057482; VEGFA rs2010963, rs1570360, rs699947, rs3025039 and rs833061; KDR rs1870377, rs2305948 and rs2071559; CCL2 rs1024611, rs1024610, rs2857657 and rs2857654; NOS3 rs1799983; ICAM1 rs5498 and rs3093030; TGFB1 rs1800469; CD53 rs6679497; POSTN rs3829365 and rs1028728; and LGALS2 rs7291467 polymorphisms, as well as their haplotype combinations, were not associated with CCC (p < 0.05).ConclusionsWe could not validate in our cohort the association of the NOS3 rs1799983, HIF1A rs11549465, VEGFA rs2010963 and rs699947, and LGALS2 rs7291467 variants with CCC reported by other authors. A validated SNP-based genome-wide association study is required to identify polymorphisms influencing CCC.

Three- and 6-month optical coherence tomographic surveillance following percutaneous coronary intervention with the Angiolite® drug-eluting stent: The ANCHOR study

Pre‐clinical results of a novel open‐cell, thin strut, durable polymer, laser cut cobalt chromium sirolimus‐eluting stent (Angiolite) were promising. Using quantitative optical coherence tomographic (OCT) analyses, we explored the healing characteristics of the Angiolite DES system at 3‐ and 6‐months post implantation.