Biomedical subjects
Publications and source records attributed to Cindy L Grines.
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BACKGROUND: Restenosis after implantation of coronary artery stents remains a significant clinical problem. We undertook a randomized, double-blind, placebo-controlled trial to determine whether cilostazol, a drug that suppresses intimal proliferation, would reduce renarrowing in patients after stent implantation in native coronary arteries. METHODS AND RESULTS: We assigned 705 patients who had successful coronary stent implantation to receive, in addition to aspirin, cilostazol 100 mg BID or placebo for 6 months; clopidogrel 75 mg daily was administered to all patients for 30 days. Restenosis was determined by quantitative coronary angiography at 6 months. The minimal luminal diameter at 6 months for cilostazol-treated patients was 1.77 mm for the analysis segment (stent plus 5-mm borders) compared with 1.62 mm in the placebo group (P=0.01). Restenosis, defined as > or =50% narrowing, occurred in 22.0% of patients in the cilostazol group and in 34.5% of the placebo group (P=0.002), a 36% relative risk reduction. Restenosis was significantly lower in cilostazol-treated diabetics (17.7% versus 37.7%, P=0.01) and in those with small vessels (23.6% versus 35.2%, P=0.02), long lesions (29.9% versus 46.6%, P=0.04), and left anterior descending coronary artery site (19.3% versus 39.8%, P=0.001). There was no difference in bleeding, rehospitalization, target-vessel revascularization, myocardial infarction, or death. CONCLUSIONS: Treatment with the drug cilostazol resulted in a significantly larger minimal luminal diameter and a significantly lower binary restenosis rate compared with placebo-treated patients. These favorable effects were apparent in patients at high risk for restenosis.
Baseline features, management, and outcomes of patients who had acute myocardial infarction (AMI) and were excluded from randomized trials of primary percutaneous coronary intervention (PCI) have not been well described. We examined the baseline features and outcomes of patients who had AMI and were excluded due to angiographic ineligibility from a randomized trial of primary PCI. The CADILLAC trial evaluated 4 primary PCI strategies in patients who had AMI without cardiogenic shock. Of 2,681 patients who consented, 599 (22.3%) were subsequently excluded from randomization due to protocol-specified angiographic findings. These patients were enrolled in a formal in-hospital registry and were treated at the discretion of attending physicians. Registry versus randomized patients were older (median age 61.9 vs 59.0 years, p = 0.002), more frequently had 3-vessel disease (52.4% vs 15.6%, p = 0.0001), and more frequently had lower left ventricular ejection fraction (45% vs 50%, p = 0.002). Registry patients were treated with PCI (n = 234), coronary artery bypass grafting (n = 136), or medically only (n = 226). In-hospital mortality rate among all patients who consented was 2.2% and was higher among registry than among randomized patients (4.0% vs 1.6%, relative risk 2.45, p = 0.001). Within the registry, covariate-adjusted risk of mortality was lower among patients who were treated by PCI compared with those who were treated medically (odds ratio 0.21, p=0.03). In conclusion, angiographic ineligibility for randomization in a large, prospective, primary PCI trial was associated with numerous high-risk demographic characteristics and higher short-term mortality. Nonetheless, the overall survival of patients who were referred for primary PCI was excellent, and performance of primary PCI versus medical therapy was associated with increased survival among excluded patients.
Little is known about the influence of stenting versus balloon angioplasty on long-term outcomes (particularly mortality) after primary percutaneous coronary intervention (PCI). We evaluated 2,087 patients with ST-elevation myocardial infarction enrolled in various Primary Angioplasty in Myocardial Infarction (PAMI) trials in the United States, who underwent primary PCI. The main outcome was all-cause mortality at 5 years, obtained through the National Death Index. Of the 2,087 patients, stenting was performed in 692 (33%). The absolute difference in the hospital (2.2% vs 3.3%), 1-year (3.3% vs 5.2%), and 5-year (10% vs 13%) mortality rates favored patients receiving a stent versus conventional balloon therapy, with the difference increasing with time. A multivariate Cox model identified stent use (vs balloon alone) as an independent correlate of lower 5-year mortality (hazard ratio 0.60, 95% confidence interval 0.42 to 0.85). The absolute reduction in mortality was greatest in the highest risk group. In conclusion, compared with balloon angioplasty, stenting during primary PCI not only resulted in better angiographic and short-term outcomes, but also in a sustained beneficial effect on mortality at 5 years. These data support the routine use of coronary stenting in most patients undergoing primary PCI, when feasible.
OBJECTIVES: We sought to investigate the benefit, predictors of procedural success, and safety of pre-procedural intra-coronary fibrin-specific lytic infusion (ICL) in patients with failed prior percutaneous coronary intervention (PCI) for chronic total occlusions (CTO). BACKGROUND: Percutaneous coronary intervention for CTO remains a challenge with a high incidence of procedural failure secondary to inability to cross the occlusion with the guidewire. METHODS: Eighty-five patients who underwent unsuccessful PCI procedures of CTO (more than three months' duration) had a repeat attempt of recanalization with the use of pre-procedural ICL. Patients received a weight-adjusted dose of either alteplase (tPA) (2 to 5 mg/h) or tenecteplase (TNK) (0.5 mg/h) for a total of 8 h. The total dose of ICL therapy was infused split between the guiding catheter and an intracoronary infusion catheter. A step-down multivariate logistic regression analysis was completed to determine the best predictors of procedural success. In-hospital major adverse cardiac events (MACE) including myocardial infarction, acute reocclusion, stroke, and death, as well as bleeding complications, were also examined. RESULTS: The procedure was successful in 46 of 85 cases (54%). Four of 85 (5%) contained dissections that did not result in perforations, tamponade, or MACE. The incidence of groin complications was 7 of 85 (8%) and of bleeding complications requiring transfusions was 3 of 85 (3.5%). On multivariate analysis, predictors of success were tapering morphology (odds ratio, 15.5; 95% confidence interval, 3.73 to 63; p = 0.0002) and lack of bridging collaterals (odds ratio, 5.08; 95% confidence interval, 1.53 to 17; p = 0.008). CONCLUSIONS: Intracoronary infusion of fibrin-specific thrombolytic therapy may provide a valuable and safe option for facilitating percutaneous revascularization of CTO.
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Thrombocytopenia that develops after percutaneous coronary intervention (PCI) may result in hemorrhagic complications, requirement for blood product transfusions, and potentially thrombotic or ischemic complications. The incidence and prognostic significance of thrombocytopenia, in patients with acute myocardial infarction (AMI) who undergo primary PCI have not been evaluated. In the CADILLAC trial 2,082 patients who had AMI within 12 hours of onset without shock were prospectively randomized to receive balloon angioplasty with or without abciximab versus stenting with or without abciximab. Acquired thrombocytopenia, defined as a nadir platelet count <100 x 10(9)/L in patients who did not have baseline thrombocytopenia, developed in 50 of 1,975 qualifying patients (2.5%) after primary PCI. By multivariate analysis, acquired thrombocytopenia developed more frequently in patients who had non-insulin-requiring diabetes mellitus (odds ratio 3.88 [OR], p = 0.0002), previous statin administration (OR 3.28, p = 0.002), and use of abciximab (OR 2.06, p = 0.02) and less frequently in patients who had previous aspirin use (OR 0.26, p = 0.002), a higher baseline platelet count (OR 1.20, p < 0.0001), and greater body mass index (OR 0.90, p = 0.006). Patients who developed thrombocytopenia versus those who did not had higher in-hospital rates of major hemorrhagic complications (10.0% vs 2.7%, p = 0.01), greater requirement for blood transfusions (10.0% vs 3.9%, p = 0.05), longer hospital stay (median 4.8 vs 3.6 days, p = 0.008), and increased costs (median dollar 14,466 vs dollar 11,629, p = 0.001). All-cause mortality was markedly increased at 30 days (8.0% vs 1.6%, p = 0.0008) and at 1 year (10.0% vs 3.9%, p = 0.03) in patients who developed thrombocytopenia. In conclusion, thrombocytopenia that develops after primary PCI for AMI, although uncommon, is associated with increased hemorrhagic complications and decreased survival.
We evaluated the prognostic effect of baseline left ventricular function and the determinants of its recovery after acute myocardial infarction (AMI) treated by primary angioplasty. Left ventriculography was performed during the index procedure in 1,620 of 2,082 patients (78%) who underwent primary angioplasty for AMI in the CADILLAC trial. One-year survival rate was significantly lower in patients whose baseline left ventricular ejection fraction (LVEF) was <40% than in those whose LVEF was > or =40% (89.0% vs 97.2%, respectively, p <0.0001). The effect of baseline left ventricular dysfunction on mortality was confined to the first 3 months after AMI; thereafter, survival was independent of baseline LVEF. By multivariate analysis, baseline LVEF (hazard ratio 0.93, 95% confidence interval 0.90 to 0.97, p <0.001) and infarct zone regional wall motion (hazard ratio 2.67, 95% confidence interval 1.08 to 6.63, p = 0.03) were independent predictors of 1-year mortality. Seven-month convalescent LVEF was also directly related to baseline LVEF and inversely correlated with previous AMI, multivessel coronary disease, preprocedural Thrombolysis In Myocardial Infarction grade 0 to 2 flow, larger infarct artery diameter, and infarct artery restenosis at follow-up. In conclusion, baseline left ventricular function measured during the index procedure is a strong independent predictor of early and late survival after primary angioplasty. Simple clinical and angiographic features readily available at the time of primary angioplasty also predict convalescent LVEF and are thus of prognostic utility.
We examined the incidence, presentation, and outcome of patients who developed gastrointestinal bleeding after percutaneous coronary intervention for acute myocardial infarction in the Primary Angioplasty in Myocardial Infarction trials. Of the 3,130 patients, 71 (2.3%) developed gastrointestinal bleeding, which was more likely to occur in elderly patients. Gastrointestinal bleeding was independently associated with a prolonged hospital stay and greater in-hospital and 6-month mortality.
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We compared the procedural success, mechanism of failure, and safety of percutaneous coronary intervention in 235 procedures for de novo chronic total occlusions with 78 procedures for chronic occlusive in-stent restenosis. Despite similar rates of procedural success and safety profile, angiographic predictors of successful percutaneous coronary intervention for de novo chronic total occlusions played a limited role in patients who had chronic occlusive in-stent restenosis, and the mechanisms of failure were different.
OBJECTIVES: We sought to develop a simple risk score for predicting mortality after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: Accurate risk stratification after primary PCI is important. Previous risk scores after reperfusion therapy have incorporated clinical +/- angiographic variables but have not considered baseline left ventricular function. Moreover, prior studies have not been validated against independent databases or studies. METHODS: The databases from the two largest multicenter, randomized AMI trials of primary PCI were utilized for score derivation (the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications [CADILLAC] trial, n = 2,082) and subsequent validation (the Stent-Primary Angioplasty in Myocardial Infarction [Stent-PAMI] trial, n = 900). Logistic regression and the jackknife procedure were used to select correlates of one-year mortality that were subsequently weighted and integrated into an integer scoring system. RESULTS: Seven variables selected from the initial multivariate model were weighted proportionally to their respective odds ratio for one-year mortality (age >65 years [2 points], Killip class 2/3 [3 points], baseline left ventricular ejection fraction <40% [4 points], anemia [2 points], renal insufficiency [3 points], triple-vessel disease [2 points], and post-procedural Thrombolysis In Myocardial Infarction flow grade [2 points]). Three strata of risk were defined (low risk, score 0 to 2; intermediate risk, score 3 to 5; and high risk, score >/=6) with excellent prognostic accuracy for survival in the derivation and validation sets (c statistics = 0.83 and 0.81 for 30-day mortality and 0.79 and 0.78 for 1-year mortality, respectively). CONCLUSIONS: In AMI patients treated with primary PCI, seven risk factors readily available at the time of intervention accurately predict short- and long-term mortality. Of note, measurement of baseline left ventricular function is the single most powerful predictor of survival and should be incorporated into risk score models.
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BACKGROUND: Women with acute myocardial infarction (AMI) undergoing primary angioplasty have higher rates of morbidity and mortality than do men. Whether contemporary interventional treatment strategies have improved outcomes for women compared with men is unknown. METHODS AND RESULTS: In the CADILLAC trial, 2082 patients (27% women) with AMI within 12 hours of symptom onset were randomized to balloon angioplasty (PTCA; n=518), PTCA+abciximab (n=528), stenting (n=512), and stenting+abciximab (n=524). As compared with men, women had a lower body surface area; had a greater prevalence of diabetes, hypertension, and hyperlipidemia; experienced significant delays to treatment; and had better baseline and final TIMI grade 3 flows. Unadjusted 1-year event rates were higher for women, including death (7.6% versus 3.0%, P<0.001), ischemic target-vessel revascularization (TVR; 16.7% versus 12.1%, P=0.006), and major adverse cardiac events (MACE; 23.9% versus 15.3%, P<0.001). Female gender was an independent predictor of MACE and bleeding complications, although comorbid risk factors and body surface area but not gender predicted 1-year death. For women, primary stenting resulted in a reduction in 1-year MACE from 28.1% to 19.1% (P=0.01) and in ischemic TVR from 20.4% to 10.8% (P=0.002) compared with PTCA. The addition of abciximab to primary stenting significantly reduced the 30-day ischemic TVR without increasing bleeding or stroke rates. CONCLUSIONS: The higher mortality rate in women compared with men after interventional treatment for AMI may be explained by differences in body size and clinical risk factors, although female gender remains an important independent determinant of overall adverse outcomes. For women in the CADILLAC trial, the addition of abciximab reduced 30-day TVR without increasing bleeding risk, and primary stenting reduced 1-year TVR and MACE rates compared with PTCA.
AIMS: ST-segment recovery (SigmaSTR) and myocardial blush (MB) evaluate different elements of microcirculatory integrity after reperfusion therapy in acute myocardial infarction (AMI). We sought to determine whether the combination of SigmaSTR and MB after primary percutaneous coronary intervention (PCI) in AMI has greater prognostic utility than either measure alone. METHODS AND RESULTS: The 30 days and 1 year clinical outcomes of 456 patients were assessed as a function of SigmaSTR and MB after primary PCI from the CADILLAC trial. SigmaSTR and MB were concordant (> or =70% SigmaSTR and MB grade 2/3 or <70% SigmaSTR and MB grade 0/1) in 60.1% of patients and discordant in 39.9% of patients. The greatest survival was observed among patients with complete SigmaSTR (> or =70%) and MB grade 2/3 in whom the cumulative rates of death at 30 days and 1 year were 0.6 and 1.2%, respectively. Poorest survival was observed among patients with incomplete SigmaSTR (<70%) and reduced MB (grade 0/1), in whom 30 days and 1 year rates of death were 8.3 and 10.1%, respectively. Intermediate outcomes were present in patients with discordant MB and SigmaSTR. By multivariable analysis, however, SigmaSTR was an independent correlate of survival at 30 days and 1 year (P=0.05 and 0.01, respectively), whereas MB was no longer predictive (P=0.38 and 0.72, respectively). CONCLUSION: SigmaSTR and MB are not infrequently discordant after primary PCI. By univariate analysis, both measures of reperfusion success strongly correlate with survival and assessment of both yields incremental prognostic information beyond either measure alone. By multivariable analysis, however, SigmaSTR is the stronger prognostic variable.
OBJECTIVES: We investigated the impact of diabetes mellitus on myocardial perfusion after primary percutaneous coronary intervention (PCI) utilizing myocardial blush grade (MBG) and ST-segment elevation resolution (STR). BACKGROUND: Diabetes is an independent predictor of outcomes after primary PCI for acute myocardial infarction (AMI). Whether the poor prognosis is due to lower rates of myocardial reperfusion is unknown. METHODS: Reperfusion success in those with and without diabetes mellitus was determined by measuring MBG (n = 1,301) and STR analysis (n = 700) in two substudies of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial among patients undergoing primary PCI for AMI. RESULTS: There were no differences between those with or without diabetes with regard to postprocedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 (>95%), distribution of infarct-related artery, and the frequency of stent deployment or abciximab administration. Patients with diabetes mellitus were more likely to have absent myocardial perfusion (MBG 0/1, 56.0% vs. 47.1%, p = 0.01) and absent STR (20.3% vs. 8.1%, p = 0.002). Diabetes mellitus (hazard ratio [HR] 1.63 [95% confidence interval (CI) 1.17 to 2.28], p = 0.004) was an independent predictor of absent myocardial perfusion (MBG 0/1) and absent STR (HR 2.94 [95% CI 1.64 to 5.37], p = 0.005) by multivariate modeling. CONCLUSIONS: Despite similar high rates of TIMI flow grade 3 after primary PCI in patients with and without diabetes, patients with diabetes are more likely to have abnormal myocardial perfusion as assessed by both incomplete STR and reduced MBG. Diminished microvascular perfusion in diabetics after primary PCI may contribute to adverse outcomes.
More than 1.2 million percutaneous coronary interventions are performed annually in the United States, with only an estimated 33% performed in women, despite the established benefits of percutaneous coronary intervention and adjunctive pharmacotherapy in reducing fatal and nonfatal ischemic complications in acute myocardial infarction and high-risk acute coronary syndromes. This statement reviews sex-specific data on the safety and efficacy of contemporary interventional therapies in women.