Thrombolysis In Myocardial Infarction Trial Research Articles

Novel Polygenic Risk Score and Established Clinical Risk Factors for Risk Estimation of Aortic Stenosis

Polygenic risk scores (PRSs) have proven to be as strong as or stronger than established clinical risk factors for many cardiovascular phenotypes. Whether this is true for aortic stenosis remains unknown. To develop a novel aortic stenosis PRS and compare its aortic stenosis risk estimation to established clinical risk factors. This was a longitudinal cohort study using data from the Million Veteran Program (MVP; 2011-2020), UK Biobank (2006-2010), and 6 Thrombolysis in Myocardial Infarction (TIMI) trials, including DECLARE-TIMI 58 (2013-2018), FOURIER (TIMI 59; 2013-2017), PEGASUS-TIMI 54 (2010-2014), SAVOR-TIMI 53 (2010-2013), SOLID-TIMI 52 (2009-2014), and ENGAGE AF-TIMI 48 (2008-2013), which were a mix of population-based and randomized clinical trials. Individuals from UK Biobank and the MVP meeting a previously validated case/control definition for aortic stenosis were included. All individuals from TIMI trials were included unless they had a documented preexisting aortic valve replacement. Analysis took place from January 2022 to December 2023. PRS for aortic stenosis (developed using data from MVP and validated in UK Biobank) and other previously validated cardiovascular PRSs, defined either as a continuous variable or as low (bottom 20%), intermediate, and high (top 20%), and clinical risk factors. Aortic stenosis (defined using International Classification of Diseases or Current Procedural Terminology codes in UK Biobank and MVP or safety event data in the TIMI trials). The median (IQR) age in MVP was 67 (57-73) years, and 135 140 of 147 104 participants (92%) were male. The median (IQR) age in the TIMI trials was 66 (54-78) years, and 45 524 of 59 866 participants (71%) were male. The best aortic stenosis PRS incorporated 5 170 041 single-nucleotide variants and was associated with aortic stenosis in both the MVP testing sample (odds ratio, 1.41; 95% CI, 1.37-1.45 per 1 SD PRS; P = 4.6 × 10-116) and TIMI trials (hazard ratio, 1.44; 95% CI, 1.27-1.62 per 1 SD PRS; P = 3.2 × 10-9). Among genetic and clinical risk factors, the aortic stenosis PRS performed comparably to most risk factors besides age, and within a given age range, the combination of clinical and genetic risk factors was additive, providing a 3- to 4-fold increased gradient of risk of aortic stenosis. However, the addition of the aortic stenosis PRS to a model including clinical risk factors only improved risk discrimination of aortic stenosis by 0.01 to 0.02 (C index in MVP: 0.78 with clinical risk factors, 0.79 with risk factors and aortic stenosis PRS; C index in TIMI: 0.71 with clinical risk factors, 0.73 with risk factors and aortic stenosis PRS). This study developed and validated 1 of the first aortic stenosis PRSs. While aortic stenosis genetic risk was independent from clinical risk factors and performed comparably to all other risk factors besides age, genetic risk resulted in only a small improvement in overall aortic stenosis risk discrimination beyond age and clinical risk factors. This work sets the stage for further development of an aortic stenosis PRS.

Predictors of No-Reflow in Patients undergoing Primary Percutaneous Coronary Intervention for Acute ST Elevation Myocardial Infarction at Tabba Heart Institute Karachi

Aim: To determine the predictors of no-reflow in patients undergoing Primary Percutaneous Coronary Intervention (PPCI) for acute ST elevation myocardial infarction (STEMI) at Tabba Heart Institute Karachi. Study duration: The study was carried out from September 2020 to September 2021. Methods: An observational study that was conducted at Tabba heart Institute Karachi. All patients with acute ST elevation myocardial infarction (STEMI) presenting within 12 hours of symptoms who undergoing primary PCI were included in the study. The patients were categorized Angiographically as no –reflow (with Thrombolysis in Myocardial Infarction (TIMI) <3 and reflow (TIMI-3) flow groups. The data regarding age and gender, type of MI, time from symptoms onset, co-morbid conditions like diabetes mellitus, hypertension, smoking, baseline Thrombolysis In Myocardial Infarction Trials (TIMI flow), infarct related artery (IRA), diameter of stent used, and the TIMI flow in IRA after the completion of procedure but before the use of intracoronary adenosine if needed, was recorded on a pre-designed proforma. The data was analyzed using SPSS 20.0. Results: Total 296 patients who underwent primary PCI after acute MI were enrolled in the study. Mean age of the study population was 57±11 years. No reflow was present in 31.4% of patients. No reflow was more common in patients with age more than 60 years, females, symptom onset to primary PCI time of more than 6 hours, LAD infarct, and baseline TIMI flow < 2. Conclusion: During primary PCI, no reflow occurs in a significant percentage of patients and is predictable by a number of factors which should be kept in mind to minimize the incidence of no reflow. Key words: No reflow, acute myocardial infarction, primary PCI

Sex, Permanent Drug Discontinuation, and Study Retention in Clinical Trials: Insights From the TIMI trials.

Women are underrepresented across cardiovascular clinical trials. Whether women are more likely than men to prematurely discontinue study drug or withdraw consent once enrolled in a clinical trial is unknown. Eleven phase 3/4 TIMI (Thrombolysis in Myocardial Infarction) trials were included (135 879 men and 51 812 women [28%]). The association between sex and premature study drug discontinuation and withdrawal of consent were examined by multivariable logistic regression after adjusting for potential confounders in each individual trial and combining the individual point estimates in random effects models. After adjusting for baseline differences, women had 22% higher odds of premature drug discontinuation (adjusted odds ratio [ORadj], 1.22 [95% CI, 1.16-1.28]; P<0.001) compared with men. Qualitatively consistent results were observed for women versus men in the placebo arms (ORadj, 1.20 [95% CI, 1.13-1.27]) and active therapy arms (ORadj, 1.23 [95% CI, 1.17-1.30)]; there was some evidence for regional heterogeneity (P interaction <0.001). Of those who stopped study drug prematurely, a similar proportion of men and women in the active arm stopped because of an adverse event (36% for both; P=0.60). Women were also more likely to withdraw consent compared with men (ORadj, 1.26 [95% CI, 1.17-1.36]; P<0.001). Women were more likely than men to prematurely discontinue study drug and withdraw consent across cardiovascular outcome trials. Premature study drug discontinuation was not explained by baseline differences by sex or a higher proportion of adverse events. Future trials should better capture reasons for drug discontinuation and withdrawal of consent to understand barriers to continued study drug use and clinical trial participation, particularly among women.

A Prospective Multicenter Randomized Trial to Assess the Effectiveness of the MagicTouch Sirolimus-Coated Balloon in Small Vessels: Rationale and Design of the TRANSFORM I Trial

AimsThe objective of the study is to assess the efficacy and safety of the novel Magic Touch sirolimus coated-balloon (SCB) when compared to the SeQuent Please Neo paclitaxel coated balloon (PCB) for the treatment of de-novo small vessel coronary artery diseases (SVD). Study designThe TRANSFORM I study is a randomized, multicenter, non-inferiority trial with the intent to enroll a total of 114 patients with a de-novo SVD (≤2.5 mm). Vessel size will be pre-screened by on-line QCA. After successful pre-dilatation without major coronary dissections (type C-F) nor Thrombolysis In Myocardial Infarction trial [TIMI] grade flow ≤2, patients will be enrolled in a 1:1 randomization to receive treatment with either the novel SCB balloon or the comparative PCB balloon. The balloon sizing will be selected according to the lumen-based approach derived from optical coherence tomography (OCT). The primary endpoint is 6-month mean net lumen diameter gain (6-month minimum lumen diameter [MLD] minus baseline MLD) assessed by quantitative coronary analysis (QCA) with non-inferiority margin of 0.3 mm in per-protocol analysis. The clinical follow-up will be conducted up to 1 year. The enrollment started in September 2020 and will complete in April 2021. ConclusionsThe TRANSFORM I trial will assess the efficacy of novel SCB in terms of non-inferiority to conventional PCB with a novel OCT measurement approach in patients with a de-novo SVD.Clinical Trial Registration URL: https://clinicaltrials.gov.Unique identifier: NCT03913832.

Outcomes of Women Compared With Men After Non–ST-Segment Elevation Acute Coronary Syndromes

BackgroundIt remains disputed whether women are at excess risk of adverse outcomes versus men after non–ST-segment elevation acute coronary syndromes (NSTEACS) or whether differences are explained by discordant risk factors. ObjectivesA sex-specific analysis of cardiovascular outcomes after NSTEACS across trials conducted by the Thrombolysis In Myocardial Infarction (TIMI) Study Group was performed to determine the impact of sex on cardiovascular outcomes in this dataset. MethodsTen TIMI trials were identified that enrolled >2,500 patients with NSTEACS within 30 days of hospitalization. Cox proportional hazards models were used to examine the association of sex with major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, or stroke) after adjusting for relevant risk factors in individual trials; point estimates were then combined by using random effects models. Individual components of the composite outcome and all-cause mortality were also analyzed. ResultsAmong 68,730 patients with NSTEACS, 19,827 (29%) were women. Women were older and more frequently had hypertension, diabetes, prior heart failure, and renal impairment than men. Before considering relevant confounders, women were at similar risk of MACE compared with men (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 0.99 to 1.09; p = 0.16) but at higher risk of all-cause death (HR: 1.12; 95% CI: 1.01 to 1.24; p = 0.03). After adjustment for baseline differences, risks of MACE (HR: 0.93; 95% CI: 0.88 to 0.98; p < 0.01) and all-cause death (HR: 0.84; 95% CI: 0.78 to 0.90; p < 0.0001) were lower among women compared with men. ConclusionsAfter accounting for cardiovascular risk factors, women enrolled in clinical trials were at lower risk of MACE than men after NSTEACS. Women, however, remain undertreated with many evidence-based therapies.

Modes and timing of death in 66 252 patients with non-ST-segment elevation acute coronary syndromes enrolled in 14 TIMI trials.

Although presenting features and early sequelae of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are well described, less is known about longer-term risks and modes of death. The purpose of this study was to characterize modes of death following NSTE-ACS in clinical trial populations. We evaluated 66252 patients with NSTE-ACS enrolled in 14 Thrombolysis in Myocardial Infarction (TIMI) trials, examining baseline characteristics and modes and timing of death. Of the 66252 patients followed for a median of 372 (interquartile range 218-521) days, 3147 (4.8%) died by the time of last follow-up. Of the 2606 patients (82.8%) with known modes of death, 75.1% were related to a cardiovascular (CV) event, 3.0% were related to a bleeding event (including intracranial haemorrhage), and 21.8% were related to a non-CV/non-bleeding event. The most common modes of CV death were sudden death (SD) and recurrent myocardial infarction (MI) (36.4% and 23.4%, respectively, of CV deaths). The proportion of CV deaths related to recurrent MI was higher in the first 30 days than it was after 30 days following NSTE-ACS (30.6% vs. 18.7%), whereas the proportion of SD was lower in the first 30 days than after 30 days (21.6% vs. 46.2%). Sudden death represents the largest proportion of CV deaths after 30 days among patients enrolled in CV clinical trials with NSTE-ACS. Further investigations aimed at defining the epidemiology of SD and developing specific therapies and management approaches to reduce SD following NSTE-ACS may be critical to reducing late mortality.

Characterization of viability, scarring and hibernation of the myocardium supplied by epicardial coronary arteries with low flow grades.

The aim of this study was to analyse the relationship between reduced coronary artery flow and myocardial viability, scarring and hibernation. Coronary flow grades and collateral vessels were scored using the thrombolysis in myocardial infarction trial (TIMI) and the Rentrop and Cohen scoring systems, respectively. N-ammonia and fluorine-18-fluorodeoxyglucose (F-FDG) are the perfusion and metabolic markers on PET, respectively. The left ventricle was divided into three coronary territories. The area with the highest N-ammonia uptake was considered the reference region. Myocardial regions with F-FDG uptake of at least 50% of the reference region were considered viable and those with F-FDG uptake less than 50% of the reference region were considered scarred. Hibernation was considered present if the viable myocardium had significant wall motion abnormality. There were 80 (71 males) patients with 240 myocardial territories. TIMI 2-3 arteries supplied 151 regions (group A), and 89 regions were supplied by TIMI 0-1 arteries (group B). Viable myocardium was present in 140 (93%) regions of group A and in 76 (85%) regions of group B (P=0.068). Scarring was present in 40 (26%) regions in group A and in 49 (55%) regions in group B (P<0.0001). Wall motion data were available in 215 regions: 133 regions in group A and 82 regions in group B. Hibernating myocardium was predicted in 36 (28%) regions in group A and in 34 (41%) regions in group B (P<0.05). Myocardial regions supplied by arteries with TIMI 0-1 are characterized by significantly increased incidence of hibernation and scarring. Video abstract: http://links.lww.com/NMC/A115.

Early detection of asymptomatic bypass graft abnormalities using a cardiac troponin I ratio following coronary artery bypass surgery.

We sought to identify the best cardiac Troponin I (cTnI) ratio to detect asymptomatic graft or anastomoses anomalies after myocardial revascularization. Patients with a rising cTnI profile, based on measurements at 6 and 12 hours (cTnI 12 hours : 6 hours ratio >1) after the last anastomosis in off-pump surgery or after cardiopulmonary bypass in on-pump surgery, underwent a coronary angiogram, despite an uncomplicated postoperative course and absence of electrocardiogram changes. The optimal threshold value for the ratio was determined using a receiving operator characteristic (ROC) curve. From April 2005 to May 2011, among 1693 patients undergoing isolated coronary artery bypass graft (CABG), 29 (1.7%) had a cTnI ratio >1 and underwent postoperative angiography. Twenty abnormalities were observed in 16 patients (55%). In the anastomoses, there were four occlusions and four stenosis. In the grafts, there were 12 stenosis: two of the Y graft anastomosis, two dissections, five hematomas and three kinking. TIMI flow grade based on results of the Thrombolysis In Myocardial Infarction trial was 3 in six patients, 1 in five, and 0 in five. In the 16 patients with lesions, the cTnI ratio was 2.1 ± 1.4 versus 1.4 ± 0.3 in patients with no lesions (p = 0.09). A ratio of 1.3 (p = 0.003) was determined by ROC curve analysis as having the greatest discriminant capacity, with associated sensitivity of 87.5% and specificity of 62%. A cTnI 12 hours : 6 hours ratio >1.3 may be indicative of these abnormalities. Early identification of these anomalies may avoid adverse outcomes.

Effect of comprehensive nursing intervention on clinical efficacy of the combination of PCI and tirofiban in patients with acute STEMI

Objective To investigate and discuss the clinical efficacy and nursing experience of the combination of tirofiban and percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods A total of 80 patients with acute STEMI who had undergone the combination of PCI and tirofiban in our hospital were selected and randomly divided into the control group (routine nursing) and the observation group (comprehensive nursing intervention),with 40 patients in each group.The blood flow perfusion thrombolysis in myocardial infarction trial (TIMI)classification,the resolution of ST-segment,and complications in the two groups were observed and compared.Results The effect rate of blood perfusion in the observation group was significantly higher that in the control group (95.0％ vs 65.0％),and the difference was statistically significant (x2 =11.25,P ＜ 0.05).The resolution rate of ST segment obviously increased in the observation group compared with the control group (85.0％ vs 65.0％),and the difference was statistically significant (x2 =4.27,P ＜ 0.05).The incidence of complications was significantly decreased in the observation group compared with the control group (7.5％ vs 25.0％),with statistical difference between the two groups (x2 =4.50,P ＜ 0.05).Conclusions For patients with acute STEMI who had undergone the combination of PCI,the effective application of comprehensive nursing intervention in the perioperative period can significantly improve the clinical efficacy and reduce the incidence of complications,which should be worthy of clinical promotion. Key words: Percutaneous coronary intervention; Nursing; Tirofiban; Myocardial infarction

Prasugrel: The Triton Shell to Soothe Platelet Reactivity

ful PCI (clopidogrel = 42; prasugrel = 41). Twelve to 24 hours after receiving the loading dose, patients treated with prasugrel presented greater platelet inhibition compared to those treated with clopidogrel evaluated with the VerifyNow-P2Y12 system [median 49 (9-78) vs. 160 (82-224), respectively, p < 0.001]. Prasugrel has greater clinical efficacy compared to clopidogrel due to its better pharmacodynamic profile. This was demonstrated by the TRITON (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel) TIMI (Thrombolysis in Myocardial Infarction) trial, which reported a significant reduction in death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (12) Yet, this reduction in the incidence of ischemic events was at the expense of a higher rate of bleeding in patients treated with prasugrel, although these patients had greater net clinical benefit. (12)

Acute Effect of Sodium Nitroprusside on Microvascular Dysfunction in Patients Who Underwent Percutaneous Coronary Intervention for Acute ST-segment Elevation Myocardial Infarction

Even in the era of thrombus aspiration and distal protection for ST-segment elevation acute myocardial infarction (STEMI), microvascular dysfunction does exist and improvement of microvascular dysfunction can improve the prognosis and/or left ventricular dysfunction. We evaluated the acute effects of nitroprusside (NTP) on coronary microvascular injury that occurred after primary percutaneous coronary intervention (PCI) for STEMI in 18 patients. The final Thrombolysis in Myocardial Infarction trial (TIMI) flow grade after PCI was 3 in 17 patients and 2 in 1 patient. The index of microcirculatory resistance (IMR) was improved significantly from 76 ± 42 to 45 ± 37 (P = 0.0006) by intracoronary NTP administration. IMR improved to the normal range (IMR < 30) in 9 patients (50%). Higher TIMI flow grade and lower IMR at baseline were observed more frequently in patients whose IMR recovered to normal range after NTP administration. NTP improved the microcirculatory dysfunction at the acute phase in patients who underwent PCI for STEMI and had final TIMI 3 flow in almost all cases.

Three Cases of Middle Cerebral Artery Occlusion Emergently Revascularized with A Balloon-expandable Coronary Bare Stent After Intravenous Tissue Plasminogen Activator

Revascularization with emergency stent placement in patients with acute middle cerebral artery occlusion is still controversial in Japan. We placed balloon-expandable coronary bare stents in 3 patients in whom revascularization was not obtained after intravenous tissue plasminogen activator therapy (IV t-PA) for acute ischemic stroke (middle cerebral artery M1 occlusion). Patient 1 was an 87-year-old woman with left hemiplegia. Her National Institutes of Health Stroke Scale score (NIHSS) was 12, and her magnetic resonance imaging diffusion-weighted image Alberta Stroke Programme Early Computed Tomography Score (MRI DWI-ASPECTS) was 8. Adequate revascularization was not obtained with IV t-PA and adjunctive percutaneous transluminal angioplasty (PTA) for right M1 occlusion, and a stent was placed 368 minutes after onset. Her Thrombolysis in Myocardial Infarction Trial (TIMI) score was 2. After 90 days, her modified Rankin scale (mRS) score was 4. Patient 2 was a 65-year-old woman with left hemiplegia. Her NIHSS score was 16, and MRI DWI-ASPECTS was 9. A stent was placed 337 minutes after onset after IV t-PA and adjunctive PTA for right M1 occlusion. Her TIMI score was 3. After 90 days, her mRS score was 3. Patient 3 was a 61-year-old woman with left hemiplegia. Her NIHSS score was 18, and MRI DWI-ASPECTS score was 7. Arterial dissection was found after IV t-PA and adjunctive PTA for the right M1 occlusion, so a stent was placed 312 minutes after onset. Her TIMI score was 2. After 90 days, her mRS score was 0. Revascularization with emergency stent placement seems likely to be successful in patients with acute middle cerebral artery occlusion, but clinical symptoms do not always improve in some cases and care is needed in selecting patients for the procedure.

Glucose-6-Phosphate Dehydrogenase (G6PDH) Deficiency in a Patient with ST-Segment Elevation Acute Myocardial Infarction Successfully Treated by Simple Thrombectomy

We report the case of an 82-year-old Sardinian woman affected by "favism" (i.e. intolerance to fava beans) with chest pain associated with persistent massive ST elevation in V2-V6 leads, admitted to our department after transfer from a rural hospital without catheterization facilities. On immediate transfer to the catheterization laboratory for primary percutaneous intervention (PCI), coronary angiogram showed proximal left anterior descending (LAD) thrombotic occlusion. In consideration of her history of glucose-6 phosphate dehydrogenase deficiency and "loss of consciousness" at a young age after taking aspirin, which contraindicated aspirin therapy, we treated this patient using a new, two-step strategy, with an emergency minimalist intervention using manual thrombectomy and intracoronary glycoprotein IIb/IIIa (GPIIbIIIa) inhibition with abciximab. Subsequent angiography control confirmed the persistence of Thrombolysis in Myocardial Infarction Trial (TIMI) grade 3 flow and the presence of an intermediate proximal LAD coronary lesion, which was not treated, also due to the persisting contraindication to aspirin. In our opinion, minimalist intervention with a thrombectomy device (especially in patients characterized by a high intracoronary thrombus burden) and/or with the use of a small balloon or gentle dilation, sustained by maximized antithrombotic therapy may represent an interesting and rational approach, allowing interventionalists to postpone stenting in the setting of primary PCI in special cases.

Prior Aspirin Use and Outcomes in Acute Coronary Syndromes

The purpose of this study was to determine whether patients taking aspirin before an acute coronary syndrome (ACS) are at higher risk of recurrent events or mortality. Controversy exists whether prior aspirin use is an independent predictor of worse outcomes in patients who experience an ACS. We evaluated 66,443 ACS patients from a merged database of previous Thrombolysis in Myocardial Infarction trials. We evaluated the differences in ACS type, total mortality, and the composite end point of death, myocardial infarction (MI), recurrent ischemia, or stroke between prior aspirin and nonprior aspirin users. We used multivariate analysis to control for differences in baseline characteristics. Prior aspirin users (n = 17,839) were older (63 years vs. 59 years) and had more coronary risk factors and evidence of coronary artery disease (MI, angina, prior intervention) than nonprior aspirin users (n = 48,604) (all p < 0.0001). Prior aspirin use was associated with less severe types of ACS at presentation (e.g., unstable angina > non-ST-segment elevation MI > ST-segment elevation MI) than their nonaspirin user counterparts (p < 0.0001). After multivariate analysis, there was no difference in total mortality between prior aspirin users and nonaspirin users at day 30 (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 0.90 to 1.13) or by the last follow-up visit (mean 328 days) (hazard ratio: 1.03; 95% CI: 0.95 to 1.11). Prior aspirin use was modestly associated with recurrent MI (OR: 1.26; 95% CI: 1.12 to 1.43) and the composite end point (OR: 1.16; 95% CI: 1.08 to 1.24). Prior aspirin use was associated with more comorbidities and coronary disease and a higher risk of recurrent MI, but not mortality. As such, it should best be considered a marker of a patient population at high risk for recurrent adverse events after ACS.

Eugene Braunwald

In the last issue of Circulation Research ,1 we heard from esteemed cardiologist Eugene Braunwald (Harvard Medical School and Brigham and Women’s Hospital, Boston, MA) about his family’s escape from Nazi-occupied Austria. Braunwald arrived in the United States with his family in 1939, aged 10. He went on to become one of the most influential and highly regarded clinical cardiovascular scientists of the last 50 years. It is safe to say that through his research, Braunwald has contributed to the survival of countless heart attack patients across the globe. In part two of this interview, we learn how Braunwald’s passion for cardiology developed and how at 80 years of age that passion, as well as his work ethic, show no signs of diminishing. ### So, a New Life in Brooklyn Began… Thankfully, we were out of danger, but my parents were now concerned about our future as strangers in a country that, contrary to current belief, was not yet out of the depression. We were as poor as the proverbial church mice, and my father had to figure out how to support us. I don’t know how, but he always managed to put bread on the table. Life was nothing like it had been in Vienna before March 1938. But, my father was a very enterprising, strongly motivated, and hard-working man, and after a few false starts, he managed, with my mother’s help, to create a second successful wholesale clothing business. ### Tell Me About Your School Days in Brooklyn I started in an elementary school and did well. In fact, I was the class Valedictorian, which was quite an honor for a relatively recent arrival. Then, I went off to Brooklyn Technical High School, an elite public high school that required passing a very tough entrance examination. ### You Were Already Leaning Toward the Sciences. At What Point Did You Decide to Study Medicine? I started high school with the desire to become an engineer. It was the “in thing” to do …

Response to Letter Regarding Article, “Impact of Pretreatment With Clopidogrel on Initial Patency and Outcome in Patients Treated With Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: A Systematic Review

We thank Dr Ryding et al for their comments on our systematic review that investigated the impact of pretreatment with clopidogrel on initial coronary patency (Thrombolysis in Myocardial Infarction trial 2/3 flow) before primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction.1 No published randomized trials on this subject exist, so we investigated the impact of clopidogrel pretreatment by comparing treatment groups in studies in which patients received pretreatment with clopidogrel with those in which patients did not. To eliminate as …

Efficacy and safety of intravenous combined with intracoronary administration of tirofiban bolus in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention

Objective:To assess the safety and efficacy of simultaneous intravenous plus intracoronary administration of tirofiban bolus for patients with acute ST-elevation myocardial infarction(STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods:Forty-three patients with acute STEMI ready to receive primary PCI were randomly divided into tirofiban IV group (intravenous tirofiban bolus only before stent deployment,n=22) or tirofiban IVIC group (intravenous plus intracoronary administration of tirofiban bolus simultaneously,n=21).The thrombolysis in myocardial infarction trial and perfusion of the myocardium were observed before and after PCI.Major adverse cardiovascular event (MACE),hemorrhage event,and thrombocytopenia were observed during hospital stay; MACE was also observed 30 days after PCI.Results:The clinical characteristics and baseline angiographic findings were similar in the two groups.After PCI,no difference was observed in the final TIMI flow grade 3,CTFC≤27,sumSTR≥70% between the two groups (P=0.951,0.933,0.666,respectively).There was no significant difference in the frequencies of MACE (P=0.101) and the left ventricular ejection fraction between the two groups (P=0.694).No major hemorrhage or severe thrombocytopenia were found in the two groups during hospital stay.The total rate of bleeding was also similar in the two groups (P=0.558).The frequencies of MACE were similar in the two groups 30 days after operation.Conclusion:Simultaneous intravenous and intracoronary administration of tirofiban bolus is safe for STEMI patients undergoing primary PCI; the short-term efficacy is similar to that of intravenous administration only.

Association of Platelet Counts on Presentation and Clinical Outcomes in ST-Elevation Myocardial Infarction (from the TIMI Trials)

Platelet activation and aggregation play pivotal roles in the thrombotic process of acute coronary syndromes. However, data regarding platelet count and its association with clinical outcomes in the setting of ST-elevation myocardial infarction (STEMI) are limited. We hypothesized that higher platelet counts on presentation would be associated with poorer clinical outcomes. Data from 10,793 patients with STEMI in the Thrombolysis In Myocardial Infarction (TIMI) trials database were analyzed. Mean platelet count on presentation was 254.8 x 10(3)/microl. Higher platelet counts were associated with higher rates of adverse clinical outcomes at 30 days. In a multivariable analysis that adjusted for confounders of platelet counts (age, gender, weight, diabetes, and smoking), higher platelet counts remained associated with an increased risk of the combined end point of death, reinfarction, and congestive heart failure. With a reference group of platelet counts <200 x 10(3)/microl, the multivariable odds ratios were 1.22 (95% confidence interval 1.05 to 1.42, p = 0.009) for platelet counts of 201 to 300 x 10(3)/microl, 1.37 (95% confidence interval 1.11 to 1.68, p = 0.002) for counts of 301 to 400 x 10(3)/microl, and 1.71 (95% confidence interval 1.16 to 2.51, p = 0.005) for counts >400 x 10(3)/microl. Further, a greater decrease in follow-up platelet counts (compared with baseline values) was independently associated with an increased risk of reinfarction at 30 days (odds ratio 1.44 for every decrease of 100 x 10(3)/microl unit of platelets, 95% confidence interval 1.13 to 1.82, p = 0.03). In conclusion, in STEMI, a higher platelet count on presentation was independently associated with adverse clinical outcomes, whereas a greater subsequent platelet count decrease was associated with an increased risk of reinfarction.

Coronary and myocardial angiography: angiographic assessment of both epicardial and myocardial perfusion.

Angiographic assessment of epicardial coronary artery blood flow has played a pivotal role in our understanding of the “time-dependent open artery hypothesis” and in the evaluation of reperfusion strategies over the past 2 decades.1–8 It has become increasingly apparent, however, that clinical outcomes are not only associated with angiographic flow in the epicardial artery, but also with angiographic flow in the myocardium.9–13 To this end, the goal of reperfusion therapies has shifted to include reperfusion downstream at the level of capillary bed, and it might be more appropriate that the hypothesis now be termed “the time dependent open artery and open microvascular hypothesis.” The goal of this article is to review angiographic methods used to evaluate myocardial ischemia and infarction and to discuss the insights into the pathophysiology of acute coronary syndromes provided by these angiographic indexes of coronary artery blood flow and myocardial perfusion. For nearly 2 decades now, the Thrombolysis In Myocardial Infarction (TIMI) flow grade classification scheme has been successfully used to assess coronary blood flow in acute coronary syndromes1 (Table). It has been a valuable tool to compare angiographic outcomes following reperfusion, and the association of the TFGs with clinical outcomes (including mortality) has been well documented.2–8 The relationship between TFG and mortality does satisfy what some consider to be 3 criteria required to validate a surrogate end point for mortality, as follows: (1) There is an association between TIMI grade 3 flow and mortality, (2) an agent such as recombinant tissue plasminogen activator improves TIMI grade 3 flow by 22% over another agent such as streptokinase, and (3) the agent tissue plasminogen activator improves mortality 1.1% over streptokinase. View this table: Definitions of the TFG and the TMPG Systems On the basis of this relationship between TIMI flow and mortality observed in the GUSTO …

Clinical outcome of percutaneous coronary intervention with antecedent mutant t-PA administration for acute myocardial infarction

Objective We investigated the acute-phrase and chronic-phase outcomes of patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with or without antecedent mutant tissue-type plasminogen (t-PA) administration. Methods Thirty-nine patients with a first AMI within 6 hours of onset were randomly assigned to the treatment group (1,600,000 IU IV monteplase, n = 19) or the nontreatment group (n = 20), followed by PCI. Clinical outcomes were then evaluated. Results Patient characteristics did not differ between the 2 groups. A significantly higher number of patients in the monteplase group achieved Thrombolysis In Myocardial Infarction trial (TIMI) grade 2 flow or more at the first angiography (84.2% vs 40.0%; P < .005), reduced number of devices (1.44 vs 1.80 devices, P < .05), and reduced procedure times (59.7 vs 86.7 minutes; P < .01), with no differences in peak creatine kinase and rates of major complications and no reflow or distal embolization. Observation over an average of 5.5 months revealed a tendency toward lower target lesion revascularization rates in the monteplase group (17.6% vs 31.6%) but no intergroup difference in rates of major complications. Pretreatment quantitative coronary angioplasty only showed a significant difference in minimal lumen diameter and percent diameter stenosis in the acute phase (1.13 mm in the monteplase group vs 0.66 mm in the nontreatment group, 57.0% vs 73.0%; P < .05). 99mTc-QGS (quantitative electrocardiographically gated single-photon emission computed tomographic scintigraphy) showed no intergroup differences in left ventricular end-diastolic volume index, end- systolic volume index, and ejection fraction in the acute and chronic phases. Conclusions Our results suggest that PCI with antecedent mutant t-PA for AMI not only accelerates reperfusion, thereby facilitating PCI, but also attenuates restenosis in the chronic phase.