Jacek Legutko

Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes.

BACKGROUND Although P2Y12 antagonists are effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes, the effect of the timing of administration--before or after coronary angiography--is not known. We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention (PCI) was indicated. METHODS We enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after randomization. Patients were randomly assigned to receive prasugrel (a 30-mg loading dose) before the angiography (pretreatment group) or placebo (control group). When PCI was indicated, an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group. RESULTS The rate of the primary efficacy end point, a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy (glycoprotein IIb/IIIa bailout) through day 7, did not differ significantly between the two groups (hazard ratio with pretreatment, 1.02; 95% confidence interval [CI], 0.84 to 1.25; P=0.81). The rate of the key safety end point of all Thrombolysis in Myocardial Infarction (TIMI) major bleeding episodes, whether related or not related to coronary-artery bypass grafting (CABG), through day 7 was increased with pretreatment (hazard ratio, 1.90; 95% CI, 1.19 to 3.02; P=0.006). The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6, respectively. Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI (69% of the patients) but increased the rate of TIMI major bleeding at 7 days. All the results were confirmed at 30 days and in prespecified subgroups. CONCLUSIONS Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).

FIRST: Fractional Flow Reserve and Intravascular Ultrasound Relationship Study.

OBJECTIVES FIRST (Fractional Flow Reserve and Intravascular Ultrasound Relationship Study) aimed to determine the optimal minimum lumen area (MLA) by intravascular ultrasound (IVUS) that correlates with fractional flow reserve (FFR) and to assess the correlation between virtual histology IVUS and FFR for intermediate coronary lesions. BACKGROUND FFR is considered the gold standard for assessing intermediate coronary lesions. Measurements of ≤0.8 are considered clinically significant and indicative of physiological ischemia. METHODS FIRST is a multicenter, prospective, international registry of patients with intermediate coronary lesions, defined as 40% to 80% stenosis by angiography. In total, 350 patients (367 lesions) were enrolled at 10 U.S. and European sites. Patients were followed through hospital discharge. RESULTS Overall, an MLA <3.07 mm(2) (64.0% sensitivity, 64.9% specificity, area under curve [AUC] = 0.65) was the best threshold value for identifying FFR <0.8. The accuracy improved when reference vessel-specific analyses were performed. An MLA <2.4 mm(2) (AUC = 0.66) was best for reference vessel diameters <3.0 mm, an MLA <2.7 mm(2) (AUC = 0.71) for reference vessel diameters of 3.0 to 3.5 mm, and an MLA <3.6 mm(2) (AUC = 0.68) for reference vessel diameters >3.5 mm. FFR correlated with plaque burden (r = -0.220, p < 0.001) but not with other plaque morphology. CONCLUSIONS Anatomic measurements by IVUS show a moderate correlation with the FFR values. The optimal cutoff for an MLA to FFR <0.8 is vessel dependent. Plaque morphology characteristics do not correlate with FFR. The utility of IVUS MLA as an alternative to FFR to guide intervention in intermediate lesions may be limited in accuracy and should be tested clinically. (Fractional Flow Reserve and Intravascular Ultrasound Relationship Study [FIRST]; NCT01153555).

Thrombus aspiration followed by direct stenting: a novel strategy of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction. Results of the Polish-Italian-Hungarian RAndomized ThrombEctomy Trial (PIHRATE Trial).

BACKGROUND Previous studies with thrombectomy showed different results, mainly due to use of thrombectomy as an additional device not instead of balloon predilatation. The aim of the present study was to assess impact of aspiration thrombectomy followed by direct stenting. METHODS Patients with ST elevation myocardial infarction (STEMI) <6 hours from pain onset and occluded infarct-related artery in baseline angiography were randomized into aspiration thrombectomy followed by direct stenting (TS, n = 100) or standard balloon predilatation followed by stent implantation (n = 96). The primary end point of the study was the electrocardiographic ST-segment elevation resolution >70% (STR > 70%) 60 minutes after primary angioplasty (percutaneous coronary intervention [PCI]). Secondary end points included angiographic myocardial blush grade (MBG) after PCI, combination of STR > 70% immediately after PCI and MBG grade 3 (optimal myocardial reperfusion), Thrombolysis In Myocardial Infarction flow after PCI, angiographic complications, and in-hospital major adverse cardiac events. RESULTS Aspiration thrombectomy success rate was 91% (crossing of the lesion with thrombus reduction and flow restoration). There was no significant difference in STR ≥ 70% after 60 minutes (53.7% vs 35.1%, P = .29). STR > 70% immediately after PCI (41% vs 26%, P < .05), MBG grade 3 (76% vs 58%, P < .03), and optimal myocardial reperfusion (35.1% vs 11.8%, P < .001) were more frequent in TS. There was no difference in between the groups in 6-month mortality (4% vs 3.1%, P = .74) and reinfarction rate (1% vs 3.1%, P = .29). CONCLUSIONS Aspiration thrombectomy and direct stenting is safe and effective in STEMI patients with early presentation (<6 hours). The angiographic parameters of microcirculation reperfusion and ECG ST-segment resolution directly after PCI were significantly better in thrombectomy group despite the lack of the difference in ST-segment resolution 60 minutes after PCI.

Mesh covered stent in ST-segment elevation myocardial infarction

AIMS The MGuard stent (bare metal stent wrapped externally with a polymer mesh sleeve) is designed to prevent distal embolisation by reducing thrombus and plaque fragments released during and post percutaneous coronary intervention (PCI). The aim of this study was to confirm the clinical feasibility, safety and performance of the MGuard stent during primary PCI for ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS The present study was a multicentre, prospective, single arm study in which 60 patients with STEMI <12 hours were enrolled. Predilatation was performed in 61.7% of the cases and thrombus aspiration in 18.3%. In one (1.7%) patient the stent could not cross the lesion. Final TIMI grade 3 flow was observed in 90.0% of patients, with myocardial blush grade 3 in 73.3% of patients and complete (>70%) ST-segment resolution 60 minutes after PCI in 61.4% of patients. In 5.0% of cases distal embolisation occurred. The total major adverse cardiac events rate during the 6-month follow-up was 1.7%. CONCLUSIONS Based on this experience, the MGuard stent implantation in STEMI patients is safe and highly effective. A larger randomised trial is warranted to confirm the clinical endpoints.

Facilitated percutaneous coronary intervention in patients with acute myocardial infarction transferred from remote hospitals

P percutaneous coronary intervention (PCI) is the preferred therapy for myocardial infarction (MI) in centers that have access to immediate invasive treatment because it confers higher patency rates, lower mortality, and lower intracranial hemorrhage rates than fibrinolysis alone.1–3 Current guidelines suggest that primary PCI could be offered as an alternative to thrombolytic therapy if performed by experienced operators within 90 30 minutes after admission.4 Recent studies have suggested that PCI for MI is superior to thrombolysis even if treatment is delayed by 120 minutes by transferring the patient to an interventional center.5,6 However, delay in restoring myocardial blood flow is known to adversely impact long-term outcome.7 If safe and feasible, restoration of myocardial blood flow by thrombolytic therapy during transfer would make longer transfer times to primary PCI acceptable without compromising myocardial salvage. In the present study we tested a combined therapy of a reduced dose of fibrinolytic drug and glycoprotein IIb/IIIa inhibitor during transfer of patients with acute MI from remote community hospitals to a routine emergency angiographic center and possible invasive treatment of MI. • • • The study was approved by the institutional review board and patients gave informed consent. Patients were enrolled at the community hospitals if: (1) they presented with an acute MI (onset of chest pain 12 hours earlier and ST elevation 1 mm in 2 contiguous electrocardiographic leads) to the emergency department of a hospital without a catheterization laboratory; (2) they had no contraindications to thrombolytic therapy and were 75 years of age; and (3) if anticipated transfer time to an interventional center was 90 minutes. Two hundred eligible patients received an IV bolus of 60 U/kg heparin (maximum 5,000), 15 mg alteplase, and 0.25 mg/kg abciximab at the remote center and were transferred, in the presence of a physician, to a single tertiary referral center for diagnostic angiography and possible PCI. Demographic data and time intervals between different stages of patient care are listed in Table 1. Infusion of alteplase (35 mg/60 min) was continued during transfer. Infusion of abciximab From the Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. This study was financed entirely by the National Health Care Agency of Poland, Krakow Regional Division, as a part of the program to improve early detection and treatment of myocardial infarction in that region of Poland. Dr. Dudek’s address is: 2nd Department of Cardiology, Kopernika Str.17, 31-501 Krakow, Poland. E-mail: mcdudek@cyf-kr.edu.pl. Manuscript received July 8, 2002; revised manuscript received and accepted August 30, 2002. TABLE 1 Baseline Demographics, Risk Factors, Clinical Characteristics, and Time Intervals Between Different Stages of Patient Care

Assessment of Culprit Plaque Temperature by Intracoronary Thermography Appears Inconclusive in Patients With Acute Coronary Syndromes

Objective—Safety and feasibility evaluation of intracoronary temperature measurements in patients with acute coronary syndromes (ACS) using a catheter based thermography system. Methods and Results—Thermography was performed in 40 patients with ACS. A 3.5-F thermography catheter containing 5 thermocouples measuring vessel wall temperature, and 1 thermocouple measuring blood temperature (accuracy 0.05°C) was used. Gradient (&Dgr;Tmax) between blood temperature (Tbl) and the maximum wall temperature during pullback was measured. The device showed satisfactory safety in ACS. Only in 16 patients (40%) &Dgr;Tmax was ≥0.1°C. In 23 patients (57.5%) the highest &Dgr;Tmax was found in the culprit segment. &Dgr;Tmax between culprit and adjacent non-culprit segments was observed in patients with transient blood flow interruption during thermography (0.11±0.03 versus 0.08±0.01; P=0.04), in contrast to patients with preserved flow (0.07±0.03 versus 0.06±0.02; P=0.058). Conclusions—The novel, technically sophisticated intracoronary thermography proved its safety and feasibility. However, we were not able to convincingly and consistently differentiate between different lesions at risk, despite a selection of lesions that should appear most distinct to differentiate. A systematic interruption of flow may be necessary to achieve diagnostic results consistently, although such requirement may unfavorably change the risk-to-benefit ratio of this developing technology.

Virtual Histology-Intravascular Ultrasound Assessment of Lesion Coverage After Angiographically-Guided Stent Implantation in Patients With ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

An occlusion or severe stenosis (angiographic culprit lesion) of the infarct-related artery is frequently located at the site of the maximum thrombus burden, whereas the origin of the plaque rupture (the true culprit) can be situated proximal or distal to it. The aim of this study was to examine stent coverage of true culprit lesions in 20 patients who underwent primary percutaneous coronary intervention and had Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow restored in the infarct-related artery by angiographically guided direct stenting. Images of lesions were obtained using virtual histology-intravascular ultrasound before and after intervention (blinded to the operator). Plaque rupture sites were identified by intravascular ultrasound in 12 lesions (60%), 11 proximal and 1 distal to the minimum luminal area (MLA). Maximum necrotic core sites were found proximal to the MLA in 16 lesions, at the MLA in 3 lesions, and distal to the MLA in 1 lesion. Plaque rupture sites were fully covered by stents in 11 lesions. Virtual histology-intravascular ultrasound-derived thin-cap fibroatheroma longitudinal geographic misses were found in 10 lesions, 7 in the proximal reference segment and in 3 patients in the proximal and distal reference segments. In conclusion, in about 50% of patients who undergo primary percutaneous coronary intervention for ST-segment elevation myocardial infarction with optimal angiographic results, the stent does not fully cover the maximum necrotic core site related to the culprit lesion.

Transportation with very long transfer delays (> 90 min) for facilitated PCI with reduced-dose fibrinolysis in patients with ST-segment elevation myocardial infarction: The Krakow Network

BACKGROUND The majority of ST-segment elevation myocardial infarction (STEMI) patients are admitted to centers without primary percutaneous coronary intervention (PCI) facilities. Purpose of the study was to determine safety and outcomes in STEMI patients with transfer delay to PCI>90 min receiving half-dose alteplase and abciximab before PCI (facilitated PCI with reduced-dose fibrinolysis). METHODS AND RESULTS Outcomes of 669 STEMI patients (<12 h chest pain, non shock, fibrinolysis eligible, <75 years) with transfer delay to PCI>90 min who received half-dose alteplase and full-dose abciximab and were immediately transferred for PCI were compared with primary PCI effects in 1311 patients with transfer delay <90 min. Mean time from symptom-onset to PCI was longer (357 ± 145 min vs. 201 ± 177; P<0.001) in facilitated PCI with reduced-dose fibrinolysis group. In-hospital and 12-month outcomes were similar in both groups, however bleeding events were more frequent in facilitated PCI group (hemorrhagic stroke 0.9% vs. 0%; P<0.001; severe+moderate 5.5% vs. 2.3%; P<0.001). CONCLUSIONS This is the first large report showing the safety and benefits of transportation with very long transfer delay (>90 min) for facilitated PCI with reduced-dose fibrinolysis in STEMI patients. In fact, pharmacological treatment (combotherapy) was effective in overcoming the deleterious effects of long time-delay on outcome, with similar survival as compared to short-time transportation, despite higher risk of major bleeding complication.

ST-segment resolution assessed immediately after primary percutaneous coronary intervention correlates with infarct size and left ventricular function in cardiac magnetic resonance at 1-year follow-up

BACKGROUND Little is known about the predictive value of electrocardiographic ST-segment resolution (STR) assessed immediately after primary percutaneous coronary intervention (PCI). The aim of the study was to analyze the value of STR and maximum single-lead ST-segment elevation assessed immediately after primary PCI in prediction of infarct size and left ventricular function in cardiac magnetic resonance (CMR) at 1-year follow-up. METHODS AND RESULTS A total of 28 patients with anterior wall ST-segment elevation myocardial infarction treated with primary PCI entered the study. There was a significant correlation of STR and maximum single-lead ST-segment elevation assessed immediately after primary PCI and CMR infarct size and left ventricular function after 1 year. When analyzed according to standard optimal reperfusion cutoff (70% for STR and 1 mm for single-lead elevation), both electrocardiographic parameters were also good predictors of CMR infarct size and left ventricular function after 1 year. CONCLUSIONS ST-segment resolution and the single-lead maximum ST-segment elevation assessed immediately after primary PCI for ST-segment elevation myocardial infarction are good predictors of infarct size and left ventricular function in 1-year follow-up.

A 12–month angiographic and optical coherence tomography follow-up after bioresorbable vascular scaffold implantation in patients with ST-segment elevation myocardial infarction

The aim of the study was to evaluate the healing process at 12 months after ABSORB™ bioresorbable vascular scaffold (BVS) implantation in patients with ST‐segment elevation myocardial infarction (STEMI).