Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

BACKGROUND: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction. METHODS: REAL-TIMI 63B (A Randomized, Placebo­controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. RESULTS: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, [IQR, 4.92-16.61], 1-sided P=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA-1.10], 1-sided P=0.30). There was no significant difference in treatment emergent serious adverse events. CONCLUSIONS: Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03578809.

How common are non-acute coronary syndrome (ACS) diagnoses in patients with suspected ACS investigated with coronary angiography in New Zealand? (ANZACS-QI 58).

BACKGROUND AND AIMS: The last two decades in New Zealand have seen increased availability of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) and early invasive coronary angiography (ICA) for other high-risk acute coronary syndrome (ACS) patients. One metric to assess the clinical appropriateness of these invasive strategies is to examine the false-positive rate for the investigation (ie, the rate of non-ACS diagnoses). METHODS: All patients presenting to New Zealand public hospitals with suspected ACS who underwent ICA between 2015 and 2019 were recorded prospectively in the All New Zealand Acute Coronary Syndrome Quality Improvement registry. The cohort was divided according to clinical impression at presentation: (1) suspected STEMI <24h and (2) other suspected ACS. The final discharge diagnosis for each patient were obtained from the registry. RESULTS: There were 6,059 (20%) patients with suspected STEMI <24h and 24,258 (80%) with other suspected ACS. Of the suspected STEMIs <24h, 90.6% had a final diagnosis of STEMI, 3.5% non-ST segment elevation ACS (NSTEACS) and only 5.9% had a non-ACS diagnosis. Of those with other suspected ACS, 80.7% had a final ACS diagnosis. Across all New Zealand district health boards (DHBs), the proportion of non-ACS diagnoses was similar for suspected STEMI presentations. However, for other suspected ACS, the proportions were higher in DHBs with rapid access to coronary interventional facilities than in those without (17.6% vs 7.0%, p<0.001). CONCLUSIONS: False-positive catheter laboratory activations for suspected STEMI patients are low across New Zealand. The differences in the proportion of non-ACS diagnoses according to DHB interventional capability for other suspected ACS requires further investigation.

Hyperbaric Oxygen Therapy Following Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) is a promising treatment modality for ischemic heart disease including myocardial infarction where outcomes are frequently poor despite early revascularization. OBJECTIVE: To compare single-photon emission computed tomography (SPECT) findings in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) treated with HBOT vs. control at 6 weeks. METHODS: In this pilot study, 24 patients were randomly allocated to HBOT (n = 13) and control groups (n = 11). Both groups underwent PPCI and were treated following the guidelines for STEMI management. The HBOT group received additional 15 and 90-minute HBOT sessions. All participants underwent SPECT at initial presentation (within 48 h of PPCI) and at follow up. RESULTS: Baseline characteristics were similar in both groups. The number of affected SPECT segments in the HBOT group at baseline and 6 weeks were 47.1 ±â€¯14.6% vs. 33.7 ±â€¯16.2%, respectively, with p = 0.039, and in the control group, the number of affected segment at these times were 55.5 ±â€¯19.5% vs. 45.9 ±â€¯17.9%, respectively, with p = 0.090. At follow-up, a decrease in the summed rest score was noted in both groups (HBOT: 20 ±â€¯6.0 vs. 12.7 ±â€¯8.1; p = 0.0017; control: 23 ±â€¯8.2 vs. 16.7 ±â€¯6.6; p = 0.031). The left ventricular ejection fraction in the HBOT group improved from 44 ±â€¯22.1% to 57.2 ±â€¯15.4% (p = 0.011) and in the control group from 45.9 ±â€¯18.2% to 55 ±â€¯12.1% (p = 0.044). CONCLUSIONS: HBOT use in STEMI patients was associated with an improvement in perfusion and an increase in ejection fraction following PPCI. These observations warrant a larger randomized clinical trial.

Effects of High-Dose Rosuvastatin on Ventricular Remodelling and Cardiac Function in ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: To investigate the effects of high-dose rosuvastatin on ventricular remodelling and cardiac function in ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS: From January 2017 to March 2019, the clinical data of 93 patients with STEMI were collected and analysed, with 46 cases in the conventional-dose group (rosuvastatin, 10 mg/d) and 47 cases in the high-dose group (rosuvastatin, 20 mg/d). Blood lipid (TC, TG, LDL-C and HDL-C), serum inflammatory markers (hs-CRP, IL-6, TNF-α and ICAM-1), ventricular remodelling markers (NT-pro BNP, MMP-9, TIMP-4 and Gal-3) and indicators of cardiac function (LVESD, LVESD, LVESV, LVEDV, IVST and LVEF) were collected from all patients at the time of admission and 8 weeks after rosuvastatin treatment. RESULTS: After treatment with rosuvastatin for 8 weeks, compared with those in conventional-dose group, the levels of TC, TG, LDL-C, hs-CRP, IL-6, TNF-α, ICAM-1, NT-pro BNP, MMP-9 and Gal-3 in the high-dose group decreased significantly (P<0.05), while the increase of HDL-C and TIMP-4 levels was more obvious (P<0.05) than that in the conventional-dose group. Moreover, LVEF was significantly higher (P<0.05) and LVESD, LVESD, LVESV, LVEDV and IVST were significantly lower (P< 0.05) after treatment than before treatment in both groups. The improvement of cardiac ultrasound results in the high-dose group was more significant than that in the conventional-dose group (P< 0.05). CONCLUSION: This study suggests that high-dose rosuvastatin was better than conventional-dose rosuvastatin for improving blood lipid metabolism, reducing the inflammatory response, and preventing and treating ventricular remodelling and myocardial fibrosis, indicating that high-dose rosuvastatin had stronger therapeutic effect on STEMI than conventional-dose rosuvastatin.

Outcomes after ST-elevation myocardial infarction presentation to hospitals with or without a routine primary percutaneous coronary intervention service (ANZACS-QI 46).

AIM: Primary percutaneous coronary intervention (PCI) is the optimal reperfusion strategy to manage ST-elevation myocardial infarction (STEMI). Where timely primary PCI cannot be achieved, an initial pharmacological reperfusion strategy is recommended with subsequent transfer to a PCI-capable hospital. The study aim was to assess STEMI outcomes according to the interventional capability of the New Zealand hospital to which patients initially present. METHODS: Nine thousand four hundred and eighty-eight New Zealand patients, aged 20-79 years, admitted with STEMI to a public hospital were identified. Patients were categorised into three groups-metropolitan hospitals with all-hours access to primary PCI (routine primary PCI cohort), metropolitan hospitals without routine access to PCI, and rural hospitals. The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiac events (MACE) and major bleeding. RESULTS: Invasive coronary angiography was more frequent in the routine primary PCI cohort compared to metropolitan hospitals without routine access to PCI and rural hospitals (90.6 vs 83.0 vs 85.0% respectively; p<0.001) and occurred more commonly on the day of admission (78.9 vs 28.7 vs 25.7% respectively; p<0.001). There were no differences in multivariable adjusted all-cause mortality, MACE or major bleeding between patients admitted to any of the hospital groupings. CONCLUSION: Outcomes after STEMI in New Zealand are similar regardless of the interventional capability of the hospital where they first present.

Metoprolol blunts the time-dependent progression of infarct size.

Early metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.

Effects of different doses of atorvastatin, rosuvastatin, and simvastatin on elderly patients with ST-elevation acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).

OBJECTIVE: To conduct a randomized double-blind prospective study to investigate effect of different doses of atorvastatin, rosuvastatin, and simvastatin on elderly patients with ST-elevation AMI after PCI. METHODS: One hundred and ninety-two AMI patients over 60 years old who underwent PCI were randomly divided into six groups: the low atorvastatin group, high atorvastatin group; low rosuvastatin group; high rosuvastatin group; low simvastatin group; high simvastatin group. Demographic data and clinical information as well as coronary angiography parameters were recorded. Plasma levels of CK-MB, BNP, ALT, and TnI were measured at 12 hr, 24 hr, and 1 week after PCI. Major cardiovascular events (MACE) were recorded and analyzed using Kaplan-Meier (K-M) curve. RESULTS: No significant differences were observed in angiographic and procedural characteristics. In all high dose groups, all levels of CK-MB, BNP, ALT, and TnI were significantly lower. However, after 1 week of PCI, only CK-MB, BNP, and TnI showed significant difference between high and low dose groups. Patients in high dose groups had significantly lower rates for surgical or percutaneous intervention, recurrence of angina, and rehospitalization. K-M curve analysis also showed cumulative incidence freedom time of overall MACE in high dose groups was significantly longer. No significant differences were found among different drugs with the same doses. CONCLUSION: Patients with higher doses had lower level of CK-MB, BNP, ALT, and TnI and lower occurrence of MACE after PCI.

Percutaneous Coronary Intervention for Left Main Coronary Disease in New Zealand: National Linkage Study of Characteristics and In-Hospital Outcomes (ANZACS-QI 38).

BACKGROUND: Approximately 5% of coronary angiographies detect LMS disease >50%. Recent randomized trials showed PCI has comparable outcomes to coronary artery bypass grafting (CABG) in low or intermediate risk candidates. In clinical practice, PCI is frequently utilized in those with prohibitive surgical risk. We reviewed contemporary national results of percutaneous coronary intervention (PCI) for left main coronary disease (LMS) disease in New Zealand. METHODS: All patients undergoing PCI for LMS disease from 01/09/2014-24/09/2017 were extracted from the All New Zealand Acute Coronary Syndrome-Quality Improvement registry with national dataset linkage, analyzing characteristics and in-hospital outcomes. RESULTS: The cohort included 469 patients, mean age 70.8 ±â€¯10.7 years, male 331 (71%), and the majority 339 (72%) were unprotected LMS. Indications include ST-elevation myocardial infarction (STEMI) 83 (18%) and NSTEMI or unstable angina 229 (49%). Compared with protected LMS, unprotected LMS were more likely to present with an acute coronary syndrome (73% versus 48%, P < 0.001), and to die in-hospital (9.4% versus 3.9%, P = 0.045). In those with unprotected LMS, in-hospital mortality after acute STEMI PCI was higher than for other indications (21.1% versus 6.1%, P < 0.001). Independent predictors of in-hospital death and major adverse cardiovascular events included STEMI, femoral access and worse renal function. CONCLUSION: Our LMS PCI cohort had high mortality rates, especially those presenting with STEMI and an unprotected LMS. This reflects the contemporary real-world practice of LMS PCI being predominantly performed in high risk patients which differs from randomized trial populations, and this should be considered before comparing with CABG outcomes.

Omega-3 intake is associated with attenuated inflammatory response and cardiac remodeling after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (ω-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether ω-3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling. METHODS: ST-elevation MI (STEMI) patients (n = 421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (ΔD5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and ω-3 intake in the last 3 months before admission. RESULTS: The intake of ω-3 below the median (< 1.7 g/day) was associated with a short-term increase in hs-C-reactive protein [OR:1.96(1.24-3.10); p = 0.004], Interleukin-2 [OR:2.46(1.20-5.04); p = 0.014], brain-type natriuretic peptide [OR:2.66(1.30-5.44); p = 0.007], left-ventricle end-diastolic volume [OR:5.12(1.11-23.52)]; p = 0.036] and decreases in left-ventricle ejection fraction [OR:2.86(1.47-6.88); p = 0.017] after adjustment for covariates. No differences were observed in the extension of infarcted mass obtained by CMRi. CONCLUSION: These findings suggest that a reduced daily intake of ω-3 may intensify outcome-determining mechanisms after STEMI, such as acute inflammatory response and late left ventricular remodeling. TRIAL REGISTRATION: Clinical Trial Registry number and website: NCT02062554 .

The functional effect of atorvastatin dose-dependent via inflammation factors on acute ST segment elevation myocardial infarction after emergency percutaneous coronary intervention.

OBJECTIVE: To investigate the effect of different doses of atorvastatin on patients with acute ST segment elevation myocardial infarction (MI) after emergency percutaneous coronary intervention (PCI). METHODS: A total of 265 patients with acute ST segment elevation MI who underwent emergency PCI were enrolled, 133 in high-dose atorvastatin administration (40 mg/day) and 132 in moderate-dose atorvastatin administration (20 mg/day). All the patients continued treatment for 1 year. The incidences of major adverse cardiovascular events (MACE) were recorded, including cardiovascular death, spontaneous MI, and unplanned revascularization. The association between clinical incidences and different doses of atorvastatin treatment was studied. RESULTS: Through tracking 1 year's treatment, the level of low-density lipoprotein cholesterol was lower in high-dose atorvastatin administration than in moderate treatment (1.6 ±â€Š0.6 vs. 1.8 ±â€Š0.6, P = 0.041). MACE significantly decreased in high-dose atorvastatin administration than in moderate treatment (9.8 vs. 18.2%, P = 0.03). Spontaneous MI was significantly more attenuated in high-dose treatment than in moderate treatment (6.8 vs. 12.8%, P = 0.03). Unplanned revascularization robustly decreased in patients with high-dose administration than those with moderate-dose treatment (5.2 vs. 8.3%, P = 0.03). There was no difference in the rate of adverse events between the two groups. CONCLUSION: For patients with acute ST segment elevation MI who underwent emergency PCI, high-dose atorvastatin could provide better performance than moderate-dose in our long-term tracking.

Changes in Coronary Plaque Composition in Patients With Acute Myocardial Infarction Treated With High-Intensity Statin Therapy (IBIS-4): A Serial Optical Coherence Tomography Study.

OBJECTIVES: This study assessed changes in optical coherence tomography (OCT)-defined plaque composition in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin treatment. BACKGROUND: OCT is a high-resolution modality capable of measuring plaque characteristics including fibrous cap thickness (FCT) and macrophage infiltration. There is limited in vivo evidence regarding the effects of statins on OCT-defined coronary atheroma composition and no evidence in the context of STEMI. METHODS: In the IBIS-4 (Integrated Biomarker Imaging Study-4), 103 patients underwent intravascular ultrasonography and OCT of 2 noninfarct-related coronary arteries in the acute phase of STEMI. Patients were treated with high-dose rosuvastatin for 13 months. Serial OCT imaging was available in 153 arteries from 83 patients. We measured FCT by using a semi-automated method. Co-primary endpoints consisted of the change in minimum FCT (measured in fibroatheromas) and change in macrophage line arc. RESULTS: At 13 months, median low-density lipoprotein cholesterol had decreased from 128 mg/dl to 73.6 mg/dl. Minimum FCT, measured in 31 lesions from 27 patients, increased from 64.9 ± 19.9 µm to 87.9 ± 38.1 µm (p = 0.008). Macrophage line arc decreased from 9.6° ± 12.8° to 6.4° ± 9.6° (p < 0.0001). The secondary endpoint, mean lipid arc, decreased from 55.9° ± 37° to 43.5° ± 33.5°. In lesion-level analyses (n = 191), 9 of 13 thin-cap fibroatheromata (TCFAs) at baseline (69.2%) regressed to non-TCFA morphology, whereas 2 of 178 non-TCFA lesions (1.1%) progressed to TCFAs. CONCLUSIONS: In this observational study, we found significant increase in minimum FCT, reduction in macrophage accumulation, and frequent regression of TCFAs to other plaque phenotypes in nonculprit lesions of patients with STEMI treated with high-intensity statin therapy.

Association Between Cardiac Catheterization Laboratory Pre-Activation and Reperfusion Timing Metrics and Outcomes in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Report From the ACTION Registry.

OBJECTIVES: The aim of this study was to describe the prevalence of pre-hospital cardiac catheterization laboratory activation and its association with reperfusion timeliness and in-hospital mortality. BACKGROUND: For patients with ST-segment elevation myocardial infarction diagnosed in the field, catheterization laboratory pre-activation may lead to more timely reperfusion and improved outcomes. METHODS: A total of 27,840 patients with ST-segment elevation myocardial infarction transported via emergency medical services to 744 percutaneous coronary intervention-capable hospitals in the ACTION Registry from January 2015 to March 2017 were evaluated, excluding patients with cardiac arrest or requiring pre-percutaneous coronary intervention intubation. Catheterization laboratory pre-activation was defined as activation >10 min prior to hospital arrival. RESULTS: Catheterization laboratory pre-activation occurred in 41% of patients (n = 11,379), with minor presenting differences between those with and without catheterization laboratory pre-activation. Compared with no catheterization laboratory pre-activation, pre-activation patients were more likely to be directly transported to the catheterization laboratory on hospital arrival (23.3% vs. 5.3%), to have shorter hospital arrival-to-catheterization laboratory arrival time (median 17 min [interquartile range (IQR): 7 to 25 min] vs. 28 min [IQR: 18 to 39 min]), to have shorter door-to-device time (40 min [IQR: 30 to 51 min] vs. 52 min [IQR: 41 to 65 min]), and to have a greater likelihood of achieving first medical contact-to-device time ≤90 min (76.6% vs. 68.6%) (p < 0.001 for all). Pre-activation was associated with lower in-hospital mortality (2.8% vs. 3.4%; p = 0.01). Patients treated at hospitals in the lowest tertile of pre-activation rates had higher mortality than those treated at hospitals in the highest tertile before and after adjustment (3.6% vs. 2.7%; adjusted odds ratio: 1.33; 95% confidence interval: 1.08 to 1.63). CONCLUSIONS: In the United States, catheterization laboratory pre-activation occurred in fewer than one-half of emergency medical services-transported patients with ST-segment elevation myocardial infarction. Its association with faster reperfusion and lower mortality supports greater use of this strategy.

Acute coronary syndrome secondary to allergic coronary vasospasm (Kounis Syndrome): a case series, follow-up and literature review.

BACKGROUND: Kounis syndrome (KS) is the concurrence of acute coronary syndrome associated with mast-cell and platelet activation in the setting of hypersensitivity and allergic or anaphylactic insults. Many drugs and environmental exposures had been reported as inducers, but various inducers and the mechanism of KS remained unknown till now. The widely used traditional Chinese medicine (TCM) as a potential sensitizer were scarcely reported to induce allergic vasospasm due to the ignorance of the linkage between traditional medicine allergy and vasospasm. CASE PRESENTATION: We described 5 rare cases of KS including unreported triggers of TCM and abortion, reported the treatment strategy and 1~4 years' follow-up results, and tried to probe into the etiology of KS. Case 1 and case 2 for the first time reported acute ST-segment elevation myocardial infarction (STEMI) caused by Chinese herbs related allergic coronary vasospasm. Case 3 reported recurrent angina following allergen contact and wheezing, indicating the internal linkage of coronary vasospasm and allergic asthma. Case 4 described a childbearing-age woman suffered refractory ischemic chest pain due to coronary vasospasm in a special period of post-abortion, the attacks suddenly disappeared when her menopause recovered. Case 5 described an isolated episode of allergic coronary vasospasm under exposure of smoking and stress, which was successfully prevented by avoiding the exposures. CONCLUSION: Kounis syndrome is not rare but rarely recognized and under-diagnosed. It is necessary to recognize KS and various inducers, especially for the patients suffering refractory vasospastic cardiac attacks concentrating in special periods. Blood test of eosinophil might contribute to diagnose KS and anti-allergic agents might be helpful for controlling KS attacks.

Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center.

BACKGROUND: Evidence suggests that oxidative stress plays a principal role in myocardial damage following ischemia/reperfusion events. Recent studies have shown that the antioxidant properties of N-acetylcysteine (NAC) may have cardioprotective effects in high doses, but-to the best of our knowledge-few studies have assessed this. OBJECTIVES: Our objective was to investigate the impact of high-dose NAC on ischemia/reperfusion injury. METHODS: We conducted a randomized double-blind placebo-controlled trial in which 100 consecutive patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) were randomly assigned to the case group (high-dose NAC 100 mg/kg bolus followed by intracoronary NAC 480 mg during PCI then intravenous NAC 10 mg/kg for 12 h) or the control group (5% dextrose). We measured differences in peak creatine kinase-myocardial band (CK-MB) concentration, highly sensitive troponin T (hs-TnT), thrombolysis in myocardial infarction (TIMI) flow, myocardial blush grade (MBG), and corrected thrombolysis in myocardial infarction frame count (cTFC). RESULTS: The peak CK-MB level was comparable between the two groups (P = 0.327), but patients receiving high-dose NAC demonstrated a significantly larger reduction in hs-TnT (P = 0.02). In total, 94% of the NAC group achieved TIMI flow grade 3 versus 80% of the control group (P = 0.03). No significant differences were observed between the two groups in terms of changes in the cTFC and MBG. CONCLUSIONS: In this study, NAC improved myocardial reperfusion markers and coronary blood flow, as revealed by differences in peak hs-TnT and TIMI flow grade 3 levels, respectively. Further studies with large samples are warranted to elucidate the role of NAC in this population. ClinicalTrials.gov identifier: NCT01741207, and the Iranian Registry of Clinical Trials (IRCT; http://irct.ir ) registration number: IRCT201301048698N8.

Effects of First High-Dose Atorvastatin Loading in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

To determine the effects of 80-mg atorvastatin administration for the first time in patients with acute ST segment elevation myocardial infarction (STEMI) before emergency percutaneous coronary intervention (PCI). A total of 118 patients with STEMI who underwent emergency PCI were enrolled in this study. The patients were divided into 80-mg group (n = 59) and 40-mg group (n = 59), according to the loading dose of atorvastatin firstly before operation. The occurrence of no-reflows and changes of HbA1c were observed preoperatively and postoperatively on second and fifth days. All patients were followed up for 1 year with major adverse cardiac events (MACE) recorded. The incidence of no-reflow in 80-mg group was obviously lower than in 40-mg group (13.56% vs. 25.42%) (χ = 4.374, P = 4.374). The preoperative HbA1c levels exhibited no significant difference between 80-mg group and 40-mg group (P > 0.05). The postoperative HbA1c levels in 2 groups showed a trend of gradual decline, which were lower in 80-mg group than in 40-mg group for second day, fifth day, first month, sixth month, and 12th month (all P < 0.05). The postoperative incidence of MACE in 80-mg group was significantly lower than in 40-mg group for sixth and 12th months (both P < 0.05). The incidence of MACE in patients with reflow in 80-mg and 40-mg groups was significantly higher than in patients with no-reflow who were in 80-mg and 40-mg groups for postoperative 12th month (both P < 0.05). The first loading high dose of atorvastatin can significantly prevent occurrence of postoperative no-reflow in patients with STEMI after PCI, reduce HbA1c levels and the incidence of MACE. Clinical randomized controlled trial with larger sample size is required to confirm this finding.

Cardioprotective effect of Malva sylvestris L. in myocardial ischemic/reprefused rats.

PURPOSE: The present investigation evaluated the cardioprotective effect of Malva sylvestris L. (MS) on myocardial ischemic/reperfusion (MI/R) in rats. METHODS: All animals were divided into four groups: the sham operated group, ischemia/reperfusion group (MI/R), and the MS (250 and 500mg/kg) treated groups, who received MS 250 and 500mg/kg intragastrically for 15 consecutive days, respectively. At the end of the protocol, concentrations of aspartate transaminase (AST), creatine kinase-MB fraction (CK-MB) and lactate dehydrogenase (LDH) were estimated in serum and the concentrations of other parameters, such as C-reactive protein, macrophage inflammatory protein 1 alpha (MIP-1α), and nitric oxide (NO) were also estimated in the blood. Tissue homogenate concentrations of inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interlukin-1ß (IL-1ß), IL-10 and IL-6 as well as oxidative stress parameters, such as lipid peroxidation, catalase, and superoxide dismutase were estimated in MI/R rats. RESULT: Significant decreases (p<0.01) in AST, LDH, and CK-MB levels were observed in the MS-treated group compared with those in the MI/R group. C-reactive protein and MIP-1α levels decreased in the MS-treated group compared with those in the MI/R group. Plasma NO level was significantly enhanced in the MS-treated group than in the MI/R group. Moreover, treatment with MS significantly reduced TNF-α, IL-1ß, and IL-6 levels and increased IL-10 levels in the MS group compared with the MI/R group. Treatment with MS also attenuated the altered oxidative stress parameters in MI/R rats. CONCLUSION: The present results indicate the cardioprotective effects of MS of reducing oxidative stress and the inflammatory response in MI/R rats.

Nutritional preconditioning by marine omega-3 fatty acids in patients with ST-segment elevation myocardial infarction: A METOCARD-CNIC trial substudy.

BACKGROUND: Marine omega-3 eicosapentaenoic acid (EPA) is readily incorporated into cardiomyocyte membranes, partially displacing the omega-6 arachidonic acid (AA). Whereas AA is a substrate for pro-inflammatory eicosanoids, the release of EPA from cell membranes generates anti-inflammatory lipid mediators, contributing to the infarct-limiting effect observed experimental models. Clinical data are lacking. METHODS: In this observational study conducted in 100 patients with a reperfused anterior ST-elevation myocardial infarction (STEMI), at hospital admission we quantified by gas-chromatography the red blood cell proportions of AA, EPA, and the AA:EPA ratio, a valid surrogate for cardiomyocyte membrane content. Patients underwent cardiac magnetic resonance imaging in the acute phase (one week post-STEMI), and at long-term (6 months) follow-up. Infarct size (delayed gadolinium enhancement) and cardiac function (left ventricular ejection fraction [LVEF]) were correlated with exposures of interest by multivariate regression analysis. RESULTS: AA:EPA ratio directly related to acute infarct size (coefficient [95% CI]: 6.19 [1.68 to 10.69], P = 0.008) and inversely to long-term LVEF (coefficient [95% CI]: − 4.02 [− 7.15 to − 0.89], P = 0.012). EPA inversely related to acute infarct size (coefficient [95% CI]: − 6.58; [− 11.46 to − 1.70]; P = 0.009), while a direct association with LVEF at follow-up (coefficient [95% CI]: 3.67 [0.25 to 7.08]; P = 0.036) was observed. CONCLUSIONS: A low AA:EPA ratio in red blood cells at the time of STEMI is associated with smaller acute infarct size and preserved long-term ventricular function. Our results are consistent with prior work in experimental models and add to the notion of omega-3 fatty acids as a healthy fat. TRIAL REGISTRATION: http://www.clinicaltrials.gov/NCT01311700