Fase Piloto do Estudo SPECTRUM. Reserva de Fluxo Fracionada Versus Angiografia para Avaliação e Conduta em Pacientes com Lesões Obstrutivas Coronárias de Grau Moderado: Racional e Desenho do Estudo / Pilot Phase of the SPECTRUM Trial. Fractional Flow Reserve vs. Angiography for Evaluation and Management of Patients with Intermediate Coronary Stenosis: Rationale and Study Design

Introdução: A despeito de suas reconhecidas limitações, a angiografia coronária invasiva é o método mais usado (muitas vezes único) para a adoção de estratégias terapêuticas em pacientes submetidos a cateterismo cardíaco diagnóstico. A mensuração de reserva de fluxo fracionada (FFR) tem sido empregada em diversos estudos, fundamentalmente no contexto de pacientes em que a avaliação angiográfica per se indica a necessidade de intervenção sobre as lesões coronárias. No entanto, o método praticamente não foi ainda testado em condições opostas, no cenário clínico em que as obstruções, angiograficamente, não indicariam intervenções. O propósito deste trabalho, a ser realizado de forma piloto em dois centros, é testar a hipótese de que também para lesões intermediárias, nas quais a angiografia não demonstra necessidade de intervenção coronária, a medida de FFR resultaria em alteração da conduta terapêutica baseada em angiografia. Métodos: Serão incluídos pacientes consecutivos e clinicamente estáveis, com doença coronária em segmento proximal e/ou médio de um ou mais vasos epicárdicos (diâmetro > 2,5 mm), apresentando obstruções entre 40 e 70%, por estimativa visual. Em seguida, a conduta terapêutica (clínica ou intervencionista) baseada em angiografia, relativamente a essas lesões, será ...

Background: Despite its well-known limitations, invasive coronary angiography remains the most used, and often times the only method used to define treatment strategies in patients undergoing diagnostic cardiac catheterization. Measurement of coronary fractional flow reserve (FFR) has been used in several studies in patients for whom an interventional the rapy strategy was determined based on angiography. However, this method has not been tested in the opposite scenario, in which the angiographic evaluation does not indicate the need for interventions. The purpose of this pilot study, to be performed in two sites, is to test the hypothesis that for intermediate injuries, in which angiography does not indicate the need for coronary intervention, measurement of FFR might change the therapeutic approach based on angiography. Methods: Consecutive clinically stable patients, with coronary disease in the proximal or middle segment of one or more epicardial vessels (diameter > 2.5 mm), with injuries between 40 and 70% by visual estimation will be enrolled in this trial. The treatment approach (clinical or interventional) based on angiography will be defined independently and by consensus of two observers. Thereafter, patients in both groups will be randomized into two subgroups: (1) maintenance of the angiography-based therapeutic strategy; and (2) use of FFR to define therapeutic strategy. Patients with FFR < 0.80 will be treated by percutaneous or surgical revascularization, whereas patients with FFR ≥ 0.80 ...

Elevated plasma fibrinogen and diabetes mellitus are associated with lower inhibition of platelet reactivity with clopidogrel.

OBJECTIVES: The goal of this study was to identify factors associated with lower platelet inhibition (PI) with clopidogrel in subjects with cardiovascular disease (CVD). BACKGROUND: A heterogeneous platelet reactivity response to clopidogrel exists, and the clinical or biochemical predictors of suboptimal PI with clopidogrel remain unclear. METHODS: This study prospectively enrolled subjects with CVD requiring treatment with clopidogrel (75 mg daily for > or =7 days or 600-mg bolus > or =24 h before recruitment). A bedside rapid platelet function assay (VerifyNow, Acccumetrics, San Diego, California) to measure maximal and clopidogrel-mediated platelet reactivity was utilized, and factors associated with lower PI were identified. RESULTS: A heterogeneous, normally distributed PI (mean 40.8 +/- 26.2%) response to clopidogrel was observed in 157 subjects (age 67.2 +/- 12.2 years; 59.9% men). Multiple variable analysis of clinical and biochemical factors known to affect platelet reactivity revealed lower PI in patients with an elevated plasma fibrinogen level (> or =375 mg/dl), diabetes mellitus, and increased body mass index (BMI) (> or =25 kg/m(2)). On testing for interaction, elevated fibrinogen level was associated with diabetic status, resulting in lower PI in diabetic patients (23.9 +/- 3.9% vs. 45.1 +/- 4.5%, p < 0.001), but not nondiabetic patients (44.7 +/- 4.4% vs. 46.3 +/- 4.8%, p = 0.244). Increased BMI remained independently associated with lower PI after clopidogrel therapy regardless of diabetic status or fibrinogen level (36.8 +/- 9.0% vs. 49.0 +/- 7.0%, p < 0.001). CONCLUSIONS: Elevated plasma fibrinogen (> or =375 mg/dl) in the presence of diabetes mellitus and increased BMI (> or =25 kg/m(2)) are associated with lower PI with clopidogrel in patients with CVD.

Clinical efficacy of drug-eluting stents in diabetic patients: a meta-analysis.

OBJECTIVES: The purpose of this study was to compare estimates for revascularization and major adverse cardiac events (MACE) (death, myocardial infarction, repeat revascularization) in diabetic patients treated with paclitaxel- and sirolimus-eluting stents (PES and SES). BACKGROUND: Outcomes in diabetic patients treated with PES and SES have not been adequately evaluated. METHODS: We searched MEDLINE/EMBASE from January 2002 to February 2007 and identified abstracts/presentations from this period at major cardiology conferences. Randomized controlled trials (RCTs) and registries were included if data for diabetic patients treated with PES or SES were available. Point estimates with 95% confidence intervals (CIs) were computed as summary statistics. RESULTS: In RCTs (13 trials; n = 2,422) similar point estimates for target lesion revascularization (TLR) (PES: 8.6%, 95% CI 6.5% to 11.3%; SES: 7.6%, 95% CI 5.8% to 9.9%) and MACE (PES: 15.4%, 95% CI 12.4% to 19.1%; SES: 12.9%, 95% CI 8.5% to 19.2%) were observed. In head-to-head trials (4 RCTs), no difference in the likelihood of TLR (PES vs. SES) was observed (odds ratio [OR] 1.37, 95% CI 0.64 to 2.9, p = 0.42). In registries (16 registries; n = 10,156), point estimates for target vessel revascularization (TVR) (PES: 5.8%, 95% CI 3.9% to 8.5%; SES: 7.2%, 95% CI 4.6% to 11.2%) and MACE (PES: 10.1%, 95% CI 7.3% to 13.8%; SES: 11.9%, 95% CI 8.6% to 16.4%) were also similar. In registries reporting outcomes with both stents (8 registries for TVR and 7 registries for MACE), the likelihood of TVR (PES vs. SES) (OR 0.77, 95% CI 0.54 to 1.10, p = 0.15) and MACE (OR 0.83, 95% CI 0.68 to 1.01, p = 0.056) were nonsignificantly lower with PES. CONCLUSIONS: This analysis of over 11,000 diabetic patients treated with drug-eluting stents demonstrates single-digit revascularization rates. Furthermore, revascularization and MACE estimates are similar with both PES and SES.

Renal frame count and renal blush grade: quantitative measures that predict the success of renal stenting in hypertensive patients with renal artery stenosis.

OBJECTIVES: This study sought to identify angiographic parameters of favorable clinical response to renal artery stenting. BACKGROUND: Stenting improves blood pressure (BP) control in patients with renal artery stenosis (RAS), but markers predicting a favorable clinical response are limited. METHODS: Renal perfusion was quantified in hypertensive patients (BP >or=140/90 mm Hg) without RAS by determining renal frame count (RFC) (angiographic frames [30 frames/s] for contrast to reach distal renal parenchyma after initial renal artery opacification) and renal blush grade (RBG) (0: none, 1: minimal, 2: normal, 3: hyperemic parenchymal blush). It was hypothesized that stenting unilateral RAS in hypertensive patients would result in decreased RFC and increased RBG, which might predict BP reduction. RESULTS: The RFC in 17 consecutive hypertensive patients without RAS (control group) (64.4 +/- 14.2 years, 12 male, 22 kidneys) was 20.1 +/- 5.4, whereas RBG was 2.33 +/- 0.66. In 24 consecutive hypertensive patients with unilateral RAS (study group) (72.7 +/- 11.3 years, 8 male), reduced RFC (26.6 +/- 9.1 to 21.4 +/- 6.7, p < 0.001) and increased RBG (1.63 +/- 0.71 to 2.13 +/- 0.85, p = 0.03) were observed after renal stenting. At 6 months, reduced BP (systolic BP 150.6 +/- 15.6 mm Hg to 128.6 +/- 15.5 mm Hg, p < 0.001; diastolic BP 77.2 +/- 15.6 mm Hg to 68.3 +/- 10.4 mm Hg, p = 0.022) without change in number of hypertensive medications was observed. Clinical responders (systolic BP reduction >15 mm Hg) had a greater decrease in RFC (7.7 +/- 4.6 vs. 1.7 +/- 5.1, p = 0.009) and 78.6% of patients with >4 RFC decrease were responders (p = 0.024). CONCLUSIONS: This study shows that quantitative indices of renal perfusion (RFC and RBG) are impaired in patients with RAS and improve after stenting, and that RFC reduction is associated with BP reduction.

Elevated plasma fibrinogen level predicts suboptimal response to therapy with both single- and double-bolus eptifibatide during percutaneous coronary intervention.

OBJECTIVES: This study sought to determine the factors associated with suboptimal platelet inhibition (PI) with single- and double-bolus eptifibatide during percutaneous coronary intervention (PCI). BACKGROUND: Although PI > or = 95% measured 10 min after glycoprotein IIb/IIIa inhibitor therapy is associated with improved outcomes following PCI, this level of PI often is not achieved. METHODS: We prospectively studied 150 patients undergoing PCI with single-bolus eptifibatide (180 microg/kg) (n = 100) and double-bolus eptifibatide (180 microg/kg administered 10 min apart) (n = 50) followed by standard infusion (2 microg/kg/min). Measuring platelet aggregation at baseline and at 10 min and 30 to 45 min after eptifibatide bolus, patients were classified as optimal responders (OPT) (> or =95% PI) or suboptimal responders (sub-OPT) (<95% PI) based on 10-min PI after final bolus. RESULTS: Suboptimal PI was achieved in 61% of patients with single-bolus eptifibatide and in 36% with double-bolus eptifibatide. In the single-bolus group, sub-OPT had higher fibrinogen levels (324 +/- 85 mg/dl vs. 259 +/- 49 mg/dl, p = 0.0002), platelet counts (221 +/- 70 vs. 186 +/- 47, p = 0.008), and white blood cell counts (7.7 +/- 2.3 vs. 6.6 +/- 1.9, p = 0.02). In the double-bolus group, sub-OPT also had higher fibrinogen levels (324 +/- 68 mg/dl vs. 278 +/- 53 mg/dl, p = 0.01) and were more likely to be smokers (38.9% vs. 9.4%, p = 0.01). Multivariable analysis showed that fibrinogen level was the only independent predictor of suboptimal PI, with fibrinogen cutoffs at 375 and 325 mg/dl predicting suboptimal PI (single-bolus: 100% and 90.0%, respectively; double-bolus: 100% and 60%, respectively) with both doses. CONCLUSIONS: During PCI, both single- and double-bolus eptifibatide provide suboptimal PI in a substantial proportion of patients. A fibrinogen level >375 mg/dl is a strong predictor of suboptimal PI.

Spontaneous multivessel coronary vasospasm leading to cardiogenic shock.

We report a case of spontaneous multivessel coronary vasospasm leading to anterior myocardial infarction and cardiogenic shock in the setting of treatment with methylphenidate and withdrawal from beta-blockers and calcium channel-antagonists. The patient was stabilized with an intra-aortic balloon pump and treated with coronary stenting and vasodilators and ultimately had an uneventful recovery. We review the diagnosis and treatment of coronary vasospasm and the implications of coronary vasoreactivity in the pathophysiology of myocardial infarction.

Treatment of recurrent pulmonary vein stenoses with endovascular stenting and adjuvant oral sirolimus.

The increasing use of radiofrequency catheter ablation for the cure of atrial fibrillation has led to iatrogenic pulmonary vein stenosis as a new clinical entity. The optimal diagnostic modality and treatment for pulmonary vein stenosis and restenosis remain unclear. We report the successful treatment of pulmonary vein restenosis following percutaneous balloon angioplasty, and for the first time, following surgical bovine pericardial patch angioplasty, with endovascular stenting and adjuvant oral sirolimus. Both patients remain asymptomatic at 1 year follow-up without evidence of restenosis.

Effectiveness and safety of glycoprotein IIb/IIIa inhibitors and clopidogrel alone and in combination in non-ST-segment elevation myocardial infarction (from the National Registry of Myocardial Infarction-4).

We investigated whether a combination of clopidogrel and glycoprotein (GP) IIb/IIIa inhibitors safely decreases hospital mortality, reinfarction, and major bleeding beyond either therapy alone in patients with non-ST-elevation myocardial infarction (NSTEMI). GP IIb/IIIa inhibitors and clopidogrel, separately, have been shown to decrease adverse outcomes in patients with non-ST-elevation acute coronary syndromes, but the need for combination therapy is uncertain. Multivariate and propensity analyses compared the frequency of death, reinfarction, and major bleeding during hospitalization in 38,691 patients with NSTEMI who were enrolled in the National Registry of Myocardial Infarction 4 from July 2000 to December 2003. Of these, 65% received GP IIb/IIIa inhibitors only, 16.1% clopidogrel only, and 18.8% combination therapy. Among patients who did not undergo percutaneous coronary intervention (PCI), the composite end point of death, reinfarction, and major bleeding was significantly lower with combination therapy than with GP IIb/IIIa inhibitors alone (odds ratio 0.77, 95% confidence interval 0.67 to 0.88). In contrast, this composite end point was significantly higher when combination therapy was employed rather than clopidogrel alone (odds ratio 1.55, 95% confidence interval 1.33 to 1.81). However, among patients who underwent PCI, the composite end point was similar between combination therapy and GP IIb/IIIa inhibitor-only groups (odds ratio 1.01, 95% confidence interval 0.89 to 1.14). Further, there was a strong trend toward a higher composite end point among patients who received combination therapy rather than clopidogrel alone (odds ratio 1.31, 95% confidence interval 0.99 to 1.72). In conclusion, commonly employed strategies using a GP IIb/IIIa inhibitor alone or with the combination of clopidogrel plus GP IIb/IIIa inhibitor in NSTEMI may not be justified in comparison with a simpler strategy of clopidogrel used alone, especially in patients who have not undergone PCI.