Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction.

BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear. METHODS: In this multicenter trial, we randomly assigned patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year. RESULTS: The mean (±SD) number of stents that were placed per patient for nonculprit lesions was 1.01±0.99 in the FFR-guided group and 1.50±0.86 in the angiography-guided group. During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively. CONCLUSIONS: In patients with STEMI undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization at 1 year. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation. (Funded by the French Ministry of Health and Abbott; FLOWER-MI ClinicalTrials.gov number, NCT02943954.).

Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial.

BACKGROUND: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI. METHODS: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290. FINDINGS: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070). INTERPRETATION: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI. FUNDING: ACTION Study Group and AstraZeneca.

Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study.

BACKGROUND: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. METHODS: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). CONCLUSION: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.

Twenty-year trends in profile, management and outcomes of patients with ST-segment elevation myocardial infarction according to use of reperfusion therapy: Data from the FAST-MI program 1995-2015.

The increased use of reperfusion therapy in ST-segment-elevation myocardial infarction (STEMI) patients in the past decades is generally considered the main determinant of improved outcomes. The aim was to assess 20-year trends in profile, management, and one-year outcomes in STEMI patients in relation with use or non-use of reperfusion therapy (primary percutaneous coronary intervention (pPCI) or fibrinolysis). METHODS: We used data from 5 one-month French nationwide registries, conducted 5 years apart from 2005 to 2015, including 8579 STEMI patients (67% with and 33% without reperfusion therapy) admitted to cardiac intensive care units in France. RESULTS: Use of reperfusion therapy increased from 49% in 1995 to 82% in 2015, with a shift from fibrinolysis (37.5% to 6%) to pPCI (12% to 76%). Early use of evidence-based medications gradually increased over the period in both patients with and without reperfusion therapy, although it remained lower at all times in those without reperfusion therapy. One-year mortality decreased in patients with reperfusion therapy (from 11.9% in 1995 to 5.9% in 2010 and 2015, hazard ratio [HR] adjusted on baseline profile 0.40; 95% CI: 0.29-0.54, P < .001) and in those without reperfusion therapy (from 25.0% to 18.2% in 2010 and 8.1% in 2015, HR: 0.33; 95% CI: 0.24-0.47, P < .001). CONCLUSIONS: In STEMI patients, one-year mortality continues to decline, both related to increased use of reperfusion therapy and progress in overall patient management. In patients with reperfusion therapy, mortality has remained stable since 2010, while it has continued to decline in patients without reperfusion therapy.

Acute Myocardial Infarction: Changes in Patient Characteristics, Management, and 6-Month Outcomes Over a Period of 20 Years in the FAST-MI Program (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) 1995 to 2015.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. METHODS: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14 423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. RESULTS: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ≤72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. CONCLUSIONS: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.

Cyclosporine before PCI in Patients with Acute Myocardial Infarction.

BACKGROUND: Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS: In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS: A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS: In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Rationale and design of the Cyclosporine to ImpRove Clinical oUtcome in ST-elevation myocardial infarction patients (the CIRCUS trial).

BACKGROUND: Both acute myocardial ischemia and reperfusion contribute to cardiomyocyte death in ST-elevation myocardial infarction (STEMI). The final infarct size is the principal determinant of subsequent clinical outcome in STEMI patients. In a proof-of-concept phase II trial, the administration of cyclosporine prior to primary percutaneous coronary intervention (PPCI) has been associated with a reduction of infarct size in STEMI patients. METHODS: CIRCUS is an international, prospective, multicenter, randomized, double-blinded, placebo-controlled trial. The study is designed to compare the efficacy and safety of cyclosporine versus placebo, in addition to revascularization by PPCI, in patients presenting with acute anterior myocardial infarction within 12 hours of symptoms onset and initial TIMI flow ≤1 in the culprit left anterior descending coronary artery. Patients are randomized in a 1:1 fashion to 2.5 mg/kg intravenous infusion of cyclosporine or matching placebo performed in the minutes preceding PCI. The primary efficacy end point of CIRCUS is a composite of 1-year all-cause mortality, rehospitalization for heart failure or heart failure worsening during initial hospitalization, and left ventricular adverse remodeling as determined by sequential transthoracic echochardiography. Secondary outcomes will be tested using a hierarchical sequence of left ventricular (LV) ejection fraction and absolute measurements of LV volumes. The composite of death and rehospitalization for heart failure or heart failure worsening during initial hospitalization will be further assessed at three years after the initial infarction. RESULTS: Recruitment lasted from April 2011 to February 2014. The CIRCUS trial has recruited 975 patients with acute anterior myocardial infarction. The 12-months results are expected to be available in 2015. CONCLUSIONS: The CIRCUS trial is testing the hypothesis that cyclosporine in addition to early revascularization with PPCI compared to placebo in patients with acute anterior myocardial infarction reduces the incidence of death, heart failure and adverse LV remodeling at one-year follow-up.

Three-Year Outcomes With Fractional Flow Reserve-Guided or Angiography-Guided Multivessel Percutaneous Coronary Intervention for Myocardial Infarction.

BACKGROUND: In patients with multivessel disease with successful primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, the FLOWER-MI trial (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of noninfarct-related artery lesions regarding the 1-year risk of death from any cause, myocardial infarction, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up. METHODS: In this multicenter trial, we randomly assigned patients with ST-segment-elevation myocardial infarction and multivessel disease with successful percutaneous coronary intervention of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577). RESULTS: After 3 years, a primary outcome event occurred in 52 of 498 patients (9.40%) in the FFR-guided group and in 44 of 502 patients (8.17%) in the angiography-guided group (hazard ratio, 1.19 [95% CI, 0.79-1.77]; P=0.4). Death occurred in 22 patients (4.00%) in the FFR-guided group and in 23 (4.32%) in the angiography-guided group (hazard ratio, 0.96 [95% CI, 0.53-1.71]); nonfatal myocardial infarction in 23 (4.13%) and 14 (2.56%), respectively (hazard ratio, 1.63 [95% CI, 0.84-3.16]); and unplanned hospitalization leading to urgent revascularization in 21 (3.83%) and 18 (3.36%; hazard ratio, 1.15 [95% CI, 0.61-2.16]), respectively. CONCLUSIONS: Although event rates in the trial were lower than expected, in patients with ST-segment-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization up to 3 years. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954.

Deleterious synergistic effects of acute heart failure and diabetes mellitus in patients with acute coronary syndrome: Data from the FAST-MI Registries.

BACKGROUND: Diabetes mellitus (DM) predisposes patients to acute myocardial infarction (AMI) and acute heart failure (AHF). AIMS: To assess correlates of AHF occurring at the early stage of AMI and synergism between early AHF and DM on 5-year mortality. METHODS: FAST-MI 2005 and 2010 included 7839 consecutive patients admitted for AMI. RESULTS: Overall, 2151 patients (27.4%) had a history of diabetes mellitus (DM), of whom 629 (29.2%) were on insulin. Patients with versus without DM were older (mean age: 70.0 vs. 64.7years; P<0.001), with more comorbidities and more severe coronary artery disease. Early AHF (pulmonary oedema or cardiogenic shock) was the most frequent in-hospital complication (12.5%) and was twice as frequent in patients with versus without DM (20.2% vs. 9.6%; adjusted odds ratio: 1.66, 95% confidence interval [CI]: 1.43-1.94; P<0.001). Among in-hospital survivors, patients with DM without AHF and those with AHF without DM had 50% increases in 5-year mortality (adjusted hazard ratio [aHR]: 1.50, 95% CI: 1.32-1.69 and aHR: 1.46, 95% CI: 1.23-1.74; both P<0.001) versus patients without DM or AHF; with the risk among those with DM and AHF being doubled (aHR: 1.97, 95% CI: 1.66-2.34; P<0.0001). CONCLUSION: Early AHF is the most frequent complication of AMI and is twice as common in patients with versus without DM. After adjustment, early AHF and DM are associated with reduced 5-year survival with synergistic effects in patients with both conditions. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov (NCT00673036 and NCT01237418).

Long-term mortality after ST-elevation myocardial infarction in the reperfusion and modern secondary prevention therapy era according to coronary artery disease extent: The FAST-MI registries.

BACKGROUND: Historical cohorts have shown extent of coronary artery disease to be a predictor of poorer outcomes in ST-segment elevation myocardial infarction. However, contemporary data in the era of reperfusion and modern secondary prevention therapy are lacking. AIM: To compare 3-year survival in patients with ST-segment elevation myocardial infarction with multivessel disease versus those with single-vessel disease. METHODS: Using data from the FAST-MI 2005, 2010 and 2015 registries, three nationwide French surveys, we included all patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention within 24hours of symptom onset. Baseline characteristics, management and 3-year all-cause mortality were analysed according to coronary status (single-, two- and three-vessel disease). RESULTS: Among 3907 patients (mean age 62.4±13.7 years; 75.9% male), patients with multivessel disease (two- or three-vessel disease) accounted for 47.9%; overall, they were older, with higher cardiovascular risk profiles. In a multivariable adjusted Cox proportional hazard regression model, only patients with three-vessel disease had a higher rate of mortality at 3 years compared with those with single-vessel disease (hazard ratio 1.52, 95% confidence interval 1.68-2.26; P<0.001). Finally, patients with multivessel disease with complete myocardial revascularization before discharge had a similar prognosis to patients with single-vessel disease (hazard ratio 1.17, 95% confidence interval 0.84-1.64; P=0.35). CONCLUSIONS: Multivessel disease still represents an important proportion of patients with ST-segment elevation myocardial infarction. Although three-vessel disease is associated with higher 3-year mortality, patients with multivessel disease and complete myocardial revascularization in the contemporary era have a 3-year risk of death similar to that in patients with single-vessel disease.

Clinical outcomes according to symptom presentation in patients with acute myocardial infarction: Results from the FAST-MI 2010 registry.

BACKGROUND: Atypical clinical presentation in acute myocardial infarction (AMI) patients is not uncommon; most studies suggest that it is associated with unfavorable prognosis. HYPOTHESIS: Long-term clinical impact differs according to predominant symptom presentation (typical chest pain, atypical chest pain, syncope, cardiac arrest, or dyspnea) in AMI patients. METHODS: FAST-MI 2010, a nationwide French registry, included 4169 patients with AMI in 213 centers at the end of 2010 (76% of active centers). Demographics, medical history, hospital management, and outcomes were compared according to predominant symptom presentation. RESULTS: Typical chest pain with no other symptom was reported in 3020 patients (68% in STEMI patients, 76% in NSTEMI patients). Atypical chest pain, dyspnea, syncope, and cardiac arrest were reported in 11%, 11%, 5%, and 1%, respectively. Patients with atypical clinical presentation had a higher cardiovascular risk profile and received fewer medications and a less invasive strategy. Using Cox multivariate analysis, atypical chest pain was not associated with higher death rate at 3 years (HR: 0.96, 95% CI: 0.69-1.33, P = 0.78), whereas cardiac arrest (HR: 2.44, 95% CI: 1.00-5.97, P = 0.05), syncope (HR: 1.70, 95% CI: 1.18-2.46, P = 0.005), and dyspnea (HR: 1.66, 95% CI: 1.31-2.10, P < 0.001) were associated with higher long-term mortality compared with patients with typical isolated chest pain. Similar trends were observed in STEMI and NSTEMI populations. CONCLUSIONS: Atypical clinical presentation is observed in about 20% of AMI patients. Cardiac arrest, dyspnea, and syncope represent independent predictors of long-term mortality in STEMI and NSTEMI populations.

French Registry on Acute ST-elevation and non-ST-elevation Myocardial Infarction 2015 (FAST-MI 2015). Design and baseline data.

BACKGROUND: The FAST-MI programme, consisting of 1-month surveys of patients admitted to hospital for acute myocardial infarction (AMI) in France, has run since 2005. AIM: To gather data on the characteristics, management and outcomes of patients hospitalized for AMI at the end of 2015 in France and to provide comparisons with the previous surveys. METHODS: Consecutive adults with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment-elevation myocardial infarction (NSTEMI) with symptom onset≤48hours were included over a 1-month period, with a possible extension of recruitment for 1 additional month. Patients with AMI following cardiovascular procedures were excluded. In all, 204 centres participated in the survey (114 community hospitals, 40 academic, 48 private clinics, 2 army hospitals), representing 78% of French centres managing AMI patients. Inclusion started from 5 October 2015. Data were collected on-site from source files by external research technicians, using an electronic case record form with automatic quality checks. Centralized biology was organized in voluntary centres to collect RNA and DNA samples, serum and stools. Long-term follow-up was organized centrally with interrogation of municipal registry offices, physicians and by direct contact with the patients or their families. RESULTS: A total of 5291 patients were included over the entire recruitment period, with 3813 included during the first month (STEMI: 49%, NSTEMI: 51%). Mean age was 66±14 years, 29% were≥75 years of age, 28% were women; 80% presented with typical chest pain. In STEMI patients, 6% received intravenous fibrinolysis and 71% underwent primary PCI. The hospital death rate was 2.7% (STEMI: 2.8%, NSTEMI: 2.5%). CONCLUSIONS: Recruitment was in line with expectations and the first data show that management has continued to evolve since the 2010 survey, with continued improvement in hospital outcomes.

Clinical significance of early thrombosis after prosthetic mitral valve replacement: a postoperative monocentric study of 680 patients.

OBJECTIVES: The aim of this study was to evaluate the incidence of early thrombosis, its prognostic significance, and the therapeutic implications. BACKGROUND: Transesophageal echocardiography (TEE) is the method of choice for detecting symptomless early postoperative thrombosis of prosthetic valves. However, the clinical significance is not yet known. METHODS: Between June 1994 and December 2000, 680 consecutive patients underwent TEE on day 9 after mechanical mitral valve replacement, to search for early thrombosis. Initially, end points were the in-hospital outcome and treatment. Patients were also evaluated 34 +/- 22 months after surgery. RESULTS: Sixty-four early thrombi were detected (9.4%). Two early obstructive were treated by redo-surgery. Sixty-two nonobstructive benefited from medical treatment. The patients were allocated into two groups as a function of the maximum size of thrombus: <5 mm in 29 patients (group A) and > or =5 mm in 35 (group B). During early follow-up, we observed one complicated course in group A and eight in group B. In the long-term survey, three complications were noted in group A and 11 in group B. Incidence of early (p = 0.027) and long-term (p = 0.04) complications were significantly different in the two subsets. CONCLUSIONS: This study confirms the incidence of early thrombi after mechanical mitral valve replacement detected by TEE. A small (<5 mm) nonobstructive thrombus seems benign, and our experience argues in favor of medical treatment. Prognosis appears more serious for large thrombi. Medically aggressive therapy and further surgery should be considered in cases of obstructive thrombosis or large and mobile nonobstructive thrombosis.

Pharmacological approaches to reperfusion therapy.

Despite the fact that numerous clinical trials investigating infarct size have been completed over the last two to three decades, the methods for treating lethal reperfusion injury efficiently have only become established very recently. After several years of accumulating evidence in experimental preparations that lethal reperfusion injury might exist, the description of the phenomenon of ischaemic post-conditioning in animal models has fully convinced us of the existence and importance of irreversible myocardial damage occurring after reflow. Transfer to the clinics was possible in small phase II trials, provided care was taken to assess the determinants of infarct size and, most importantly, to consider the timing of drug administration with respect to the time of reflow. Technical questions remain to be resolved regarding the assessment of the area at risk in the difficult setting of emergency care for reperfusion therapy. Nevertheless, convincing pharmacological trials are being performed that mark the start of a new era that will, in the future, improve the prognosis of patients with ST-segment elevation myocardial infarction through the prevention of lethal myocardial reperfusion injury. At present, while erythropoietin and adenosine have not proved efficient for alleviation of lethal reperfusion injury, a significant benefit has been reported for cyclosporin and exenatide. New pharmacological agents need to be identified and tested in phase II trials. In the meantime, clinical outcome studies are currently being conducted for cyclosporin.

Cardiac magnetic resonance imaging for the diagnosis of patients presenting with chest pain, raised troponin, and unobstructed coronary arteries.

To evaluate the incremental diagnostic and prognostic value of cardiac magnetic resonance (CMR) in patients with chest pain, raised troponin and unobstructed coronary arteries, and to compare subsequent event rates between diagnostic groups. 130 patients (mean age: 54 ± 17) presenting with troponin-positive acute chest pain and unobstructed coronary arteries were included. All patients were managed according to European Society of Cardiology guidelines, including echocardiography, and had CMR within 6.2 ± 5.3 days of presentation. During follow-up, major adverse cardiovascular events (MACE) were recorded. CMR provided a diagnosis in 100 of 130 patients (76.9%), with the remaining 30 (23.1%) having a normal examination. CMR diagnosed 37 (28.5%) acute myocardial infarctions, 34 (26.1%) myocarditis, 28 (21.5%) apical ballooning syndromes and 1 (0.8%) hypertrophic cardiomyopathy. When a single diagnosis was suspected by the referring physician, CMR validated this diagnosis in 32 patients (76.2%). CMR provided a formal diagnosis in 61 patients (69.3%) in which the clinical diagnosis was uncertain between at least two possibilities. CMR corrected a wrong diagnosis in 10 patients (7.7%). CMR-suggested diagnosis led to a modification of therapy in 42 patients (32.3%). Median follow-up was 34 months (interquartile range 24-49) in 124 patients. Sixteen patients (12.9%) experienced MACE. MACE rate was not different between patients with a conclusive CMR and normal CMR. In patients with acute troponin-positive chest pain and unobstructed coronary arteries, early CMR has important diagnostic and therapeutic implications. However its association with occurrence of MACE during mid term follow-up was not obvious.

Early characterization of atherosclerotic coronary plaques with multidetector computed tomography in patients with acute coronary syndrome: a comparative study with intravascular ultrasound.

We compared 16-slice computed tomography (CT) with intravascular ultrasound (IVUS) in their ability to identify the culprit lesion, and to assess plaque characterization and vascular remodelling in acute coronary syndrome (ACS). Twenty patients were prospectively studied. Coronary plaque identification and characterization were compared using 16-slice CT and 40-MHz catheter-based IVUS. Minimum lumen area (MLA), cross-sectional vessel area (CVA) and vessel remodelling were determined for each comparable lesion. One hundred and sixty-nine segments were compared and 84 plaques analysed. Sixteen-slice CT detected 95% of culprit lesions (19/20). No feature suggestive of plaque rupture was detected by 16-slice CT. Attenuation measurements within all lesions revealed different values for hypoechoic (38 +/- 33 HU), hyperechoic (94 +/- 44 HU), and calcified plaques (561 +/- 216 HU), (P < 0.001). Agreement between 16-slice CT and IVUS on measuring MLA and CVA was evaluated using Bland-Altman analysis. Pearson and intra-class coefficient (ICC) were 0.81 and 0.70 for MLA, and 0.81 and 0.36 for CVA, for 16-slice CT and IVUS, respectively. Agreement between both techniques for vessel positive remodelling was moderate (kappa = 0.54, P < 0.001). Sixteen-slice CT has shown moderate accuracy in quantifying and characterizing coronary plaques compared with IVUS. Spatial resolution of 16-slice CT remains a major limitation, however, to accurately assess the complex lesions involved in ACS.

Prehospital administration of enoxaparin before primary angioplasty for ST-elevation acute myocardial infarction.

We hypothesized that primary percutaneous coronary intervention (PCI) could be performed with prehospital injections of enoxaparin for ST segment elevation myocardial infarction (STEMI). Enoxaparin has been studied in combination with fibrinolysis in STEMI, but has not been evaluated as anticoagulant regimen for primary PCI. In a prospective registry, 143 consecutive patients with STEMI received prehospital 0.5 mg/kg intravenous (i.v.) bolus followed by 1 mg/kg subcutaneous enoxaparin before immediate transport for PCI. We focused on anti-Xa activities before and after PCI, bleedings, infarct-related artery patency, and major adverse cardiac events at day 30. Anti-Xa activity was at the target level (>0.5 IU/ml) in 99% of patients during PCI, and in 100% 4 hr after injections; over-anticoagulation (>1.5 IU/ml) was noted in 9 and 2%, respectively at start and 4 hr after injections. Bleeding complications with enoxaparin were rare: major in 1.4% (no intracranial hemorrhages), minor in 2.1%. A patent infarct-related artery (TIMI 2 + 3) was observed in 40.6% of the patients before PCI. TIMI 3 flow was obtained in 88.1% of the cases after PCI. Major adverse cardiac events at 30 days occurred in 5.6% of cases: death 2.8%, reinfarction 3.5%, and target lesion revascularisation 3.5%. Prehospital i.v. and subcutaneous enoxaparin provides simple and rapid anticoagulation for PCI in STEMI patients. Enoxaparin dose needs to be reduced regarding the 9% of over-anticoagulation. This study suggests the potential of enoxaparin as an alternative anticoagulant regimen for primary PCI.