Selected CD133⁺ progenitor cells to promote angiogenesis in patients with refractory angina: final results of the PROGENITOR randomized trial.

RATIONALE: Refractory angina constitutes a clinical problem. OBJECTIVE: The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133(+) cells to foster angiogenesis in patients with refractory angina. METHODS AND RESULTS: In this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte colony-stimulating factor, underwent an apheresis and electromechanical mapping, and were randomized to receive treatment with CD133(+) cells or no treatment. The primary end point was the safety of transendocardial injection of CD133(+) cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6 months. Secondary end points analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6 months, 1 patient in each group had ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters; however, the comparison within groups showed a significant improvement in the number of angina episodes per month (median absolute difference, -8.5 [95% confidence interval, -15.0 to -4.0]) and in angina functional class in the treatment arm but not in the control group. At 6 months, only 1 simple-photon emission computed tomography (SPECT) parameter: summed score improved significantly in the treatment group at rest and at stress (median absolute difference, -1.0 [95% confidence interval, -1.9 to -0.1]) but not in the control arm. CONCLUSIONS: Our findings support feasibility and safety of transendocardial injection of CD133(+) cells in patients with refractory angina. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial.

Disturbed coronary hemodynamics in vessels with intermediate stenoses evaluated with fractional flow reserve: a combined analysis of epicardial and microcirculatory involvement in ischemic heart disease.

BACKGROUND: In chronic ischemic heart disease, focal stenosis, diffuse atherosclerotic narrowings, and microcirculatory dysfunction (MCD) contribute to limit myocardial flow. The prevalence of these ischemic heart disease levels in fractional flow reserve (FFR) interrogated vessels remains largely unknown. METHODS AND RESULTS: Using intracoronary measurements, 91 coronaries (78 patients) with intermediate stenoses were classified in 4 FFR and coronary flow reserve (CFR) agreement groups, using FFR>0.80 and CFR<2 as cutoffs. Index of microcirculatory resistance (IMR) and atherosclerotic burden (Gensini score) were also assessed. MCD was assumed when IMR≥29.1 (75(th) percentile). Fifty-four (59.3%) vessels had normal FFR, from which only 20 (37%) presented both normal CFR and IMR. Among vessels with FFR>0.80, most (63%) presented disturbed hemodynamics: abnormal CFR in 28 (52%) and MCD in 18 (33%). Vessels with FFR>0.80 presented higher IMR [adjusted mean 27.6 (95% confidence interval, 23.4-31.8)] than those with FFR≤0.80 [17.3 (95% confidence interval, 13.0-21.7), p=0.001]. Atherosclerotic burden was inversely correlated with CFR (r=-0.207, P=0.055), and in vessels with FFR>0.80 and CFR<2 (n=28, 39%), IMR had a wide dispersion (7-72.7 U), suggesting a combination of diffuse atherosclerotic narrowings and MCD. Vessels with FFR≤0.80 and normal CFR presented the lowest IMR, suggesting a preserved microcirculation. CONCLUSIONS: A substantial number of coronary arteries with stenoses showing an FFR>0.80 present disturbed hemodynamics. Integration of FFR, CFR, and IMR supports the existence of differentiated patterns of ischemic heart disease that combine focal and diffuse coronary narrowings with variable degrees of MCD.

Assessment of microcirculatory remodeling with intracoronary flow velocity and pressure measurements: validation with endomyocardial sampling in cardiac allografts.

BACKGROUND: Intracoronary physiology techniques have been validated extensively for the assessment of epicardial stenoses but not for the lone study of coronary microcirculation. We performed a comparison between 4 intracoronary physiological indices with the actual structural microcirculatory changes documented in transplanted hearts. METHODS AND RESULTS: In 17 cardiac allograft patients without coronary stenoses, ECG, intracoronary Doppler flow velocity, and aortic pressure were digitally recorded before and during maximal hyperemia with a dedicated system. Postprocessing of data yielded 4 indices of microcirculatory status: coronary flow velocity reserve (2.13+/-0.59), instantaneous hyperemic diastolic velocity pressure slope (2.33+/-1.25 cm x s x (-1)mm Hg(-1)), coronary resistance index (1.65+/-0.88 mm Hg x cm(-1) x s(-1)), and coronary resistance reserve (2.36+/-0.65). Quantitative morphometry was performed in endomyocardial biopsies during the same hospital intake; arteriolar obliteration (76.57+/-6.95%) and density (2.00+/-1.22 arterioles per 1 mm(2)) and capillary density (645+/-179 capillaries per 1 mm(2)) were measured. Univariate regression analysis between intracoronary measurements and histological findings revealed that instantaneous hyperemic diastolic velocity-pressure slope correlated with arteriolar obliteration (r=0.58, P=0.014) and capillary density (r=0.60, P=0.012). Statistical adjustment revealed an independent contribution of arteriolar obliteration (beta=0.61, P=0.0009) and capillary density (beta=-0.60, P=0.0008) to instantaneous hyperemic diastolic velocity-pressure slope values, resulting in an excellent predictive model (r=0.84, P=0.0002). Coronary resistance index correlated only with capillary density (r=0.70, P=0.019). Relative indices (coronary flow velocity reserve and coronary resistance reserve) did not correlate significantly with arteriolar obliteration, capillary density, or arteriolar density. CONCLUSIONS: Intracoronary indices derived from pressure and flow, particularly instantaneous hyperemic diastolic velocity-pressure slope, appear to be superior to coronary flow velocity reserve in detecting structural microcirculatory changes. Both arteriolar obliteration and capillary rarefaction seem to influence microcirculatory hemodynamics independently.

Sirolimus-eluting stents versus bare-metal stents in patients with in-stent restenosis: results of a pooled analysis of two randomized studies.

BACKGROUND: Treatment of patients with in-stent restenosis (ISR) remains a challenge. We sought to compare results of sirolimus-eluting stents (SES) with those of bare-metal stents (BMS) in patients with ISR. METHODS: The results obtained in the stent arm of two randomized studies were analyzed. The RIBS I study (450 patients with ISR) allocated 224 patients to BMS; the RIBS II study (150 patients with ISR) allocated 76 patients to SES. Complete 1-year follow-up was obtained in all 300 patients treated with stents. RESULTS: Although inclusion/exclusion criteria were identical in the two studies, when compared with patients in the BMS group, patients in the SES arm had more adverse baseline characteristics, more diffuse lesions, and smaller vessels. However, late angiographic findings including in-segment recurrent restenosis rate (11 vs. 38%, P < 0.001), minimal lumen diameter (2.52 vs. 1.63 mm, P < 0.001), and late loss (0.13 vs. 1.04 mm, P < 0.001) were significantly better after SES. The 1-year event-free survival was also significantly improved in the SES group (88 vs. 78%, P < 0.05), as the result of a lower requirement for repeated revascularizations (10.5 vs. 19.6%, P < 0.05). Prespecified subgroup analyses were consistent with the main outcome measures. After adjusting for (a) imbalances in baseline characteristics (restenosis OR 0.11 [95% confidence interval (CI) 0.03-0.36]; adverse events hazard ratios (HR) 0.33 [95% CI 0.13-0.84]) and (b) the propensity score (restenosis OR 0.08 [95% CI 0.03-0.28]; adverse events HR 0.24 [95% CI 0.09-0.66]), results of the SES group were superior to those obtained in the BMS group. CONCLUSIONS: When compared with BMS, SES improved the long-term clinical and angiographic outcome of patients with ISR.

Clopidogrel withdrawal is associated with proinflammatory and prothrombotic effects in patients with diabetes and coronary artery disease.

Inhibition of the P2Y12 pathway by the platelet antagonist clopidogrel is associated with a marked reduction in platelet reactivity. Recent reports have shown that P2Y12 inhibition has anti-inflammatory effects as well. However, whether clopidogrel withdrawal is associated with proaggregatory and proinflammatory effects has not yet been explored. Since diabetic subjects are characterized by a prothrombotic and proinflammatory status, we hypothesize that these patients may be more vulnerable to these effects. A total 54 patients with diabetes on long-term (12 months) dual antiplatelet therapy (aspirin plus clopidogrel) were studied. Platelet aggregation (following 6 and 20 micromol/l ADP stimuli) and inflammatory markers (C-reactive protein and P-selectin expression) were assessed before and 1 month following clopidogrel withdrawal. Following clopidogrel withdrawal, aspirin responsiveness using platelet function analyzer-100 was determined as well. A significant increase in all the assessed platelet (P < 0.0001 for 6 and 20 micromol/l ADP-induced aggregation) and inflammatory (P < 0.05 for C-reactive protein, P < 0.001 for P-selectin expression in resting platelets, and P < 0.0001 for P-selectin expression in ADP-stimulated platelets) biomarkers was observed following clopidogrel withdrawal. Low responders to aspirin had increased platelet aggregation profiles (P < 0.05 for 6 and 20 micromol/l ADP-induced aggregation) but no differences in inflammatory markers. In conclusion, clopidogrel withdrawal is associated with an increase in platelet and inflammatory biomarkers in diabetic patients, supporting pleiotropic effects coupled with P2Y12 receptor antagonism.

Contribution of gene sequence variations of the hepatic cytochrome P450 3A4 enzyme to variability in individual responsiveness to clopidogrel.

OBJECTIVE: Metabolic activity of cytochrome P450 (CYP) 3A4 has been associated with clopidogrel response variability. Because metabolic activity of CYP3A4 is genetically regulated, we hypothesized that genetic variations of this enzyme may contribute to clopidogrel response variability. METHODS AND RESULTS: The CYP3A4*1B, CYP3A4*3, IVS7+258A>G, IVS7+894C>T, and IVS10+12G>A polymorphisms of the CYP3A4 gene were assessed in 82 patients in a steady phase of clopidogrel therapy. Glycoprotein (platelet glycoprotein (GP) IIb/IIIa receptor activation and platelet aggregation were assessed. A cohort of 45 clopidogrel-naïve patients was studied to determine the modulating effects of these polymorphisms after loading dose (300 mg) administration. Only the IVS7+258A>G, IVS7+894C>T, and IVS10+12G>A polymorphisms were sufficiently polymorphic. During the steady phase of clopidogrel treatment, IVS10+12A allele carriers had reduced GP IIb/IIIa activation (P=0.025) and better responsiveness (P=0.02); similarly, clopidogrel-naïve patients carriers of the IVS10+12A allele had reduced GP IIb/IIIa activation during the first 24 hours after a loading dose (P=0.025), increased platelet inhibition (P=0.006), and a more optimal drug response (P=0.003). This polymorphism did not influence platelet aggregation profiles. No association was observed between the other polymorphisms and clopidogrel responsiveness. CONCLUSIONS: The IVS10+12G>A polymorphism of the CYP3A4 gene modulates platelet activation in patients treated with clopidogrel and may therefore contribute to clopidogrel response variability.

Randomized comparison of sirolimus-eluting stent versus standard stent for percutaneous coronary revascularization in diabetic patients: the diabetes and sirolimus-eluting stent (DIABETES) trial.

BACKGROUND: Outcomes after percutaneous coronary interventions in diabetic patients are shadowed by the increased rate of recurrence compared with nondiabetic patients. METHODS AND RESULTS: We conducted a multicenter, randomized trial to demonstrate the efficacy of sirolimus-eluting stents compared with standard stents to prevent restenosis in diabetic patients with de novo lesions in native coronary arteries. The primary end point of the trial was in-segment late lumen loss as assessed by quantitative coronary angiography at 9-month follow-up. The trial was stratified by diabetes treatment status. One hundred sixty patients were randomized to sirolimus-eluting stents (80 patients; 111 lesions) or standard stent implantation (80 patients; 110 lesions). On average, reference diameter was 2.34+/-0.6 mm, lesion length was 15.0+/-8 mm, and 13.1% of lesions were chronic total occlusions. In-segment late lumen loss was reduced from 0.47+/-0.5 mm for standard stents to 0.06+/-0.4 mm for sirolimus stents (P<0.001). Target-lesion revascularization and major adverse cardiac event rates were significantly lower in the sirolimus group (31.3% versus 7.3% and 36.3% versus 11.3%, respectively; both P<0.001). Non-insulin- and insulin-requiring patients demonstrated similar reductions in angiographic and clinical parameters of restenosis after sirolimus-eluting stent implantation. During the 9-month follow-up, stent thrombosis occurred in 2 patients after standard stent implantation. Conversely, this phenomenon was not seen in the sirolimus stent group. CONCLUSIONS: This randomized trial demonstrated that sirolimus stent implantation is safe and efficacious in reducing both angiographic and clinical parameters of restenosis compared with standard stents in diabetic patients with de novo coronary stenoses.

Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment.

To assess platelet function profiles in diabetic and nondiabetic patients on aspirin and clopidogrel therapy, two patient populations were included to investigate the 1) acute effects of a 300-mg clopidogrel loading dose (group 1, n = 52) and 2) long-term effects of clopidogrel (group 2, n = 120) on platelet function in diabetic compared with nondiabetic patients already on aspirin treatment. Patients were stratified according to the presence of type 2 diabetes. Platelet aggregation was assessed using light transmittance aggregometry (groups 1 and 2). Platelet activation (P-selectin expression and PAC-1 binding) was determined using whole-blood flow cytometry (group 2). Clopidogrel response was also assessed. In group 1, platelet aggregation was significantly increased in diabetic (n = 16) compared with nondiabetic (n = 36) patients at baseline and up to 24 h following a 300-mg loading dose (P = 0.005). In group 2, platelet aggregation and activation were increased in diabetic (n = 60) compared with nondiabetic (n = 60) subjects (P < 0.05 for all platelet function assays). Diabetic subjects had a higher number of clopidogrel nonresponders (P = 0.04). Diabetic patients have increased platelet reactivity compared with nondiabetic subjects on combined aspirin and clopidogrel treatment. Reduced sensitivity to antiplatelet drugs may contribute to the increased atherothombotic risk in diabetic patients.

Drug-eluting stent thrombosis: results from a pooled analysis including 10 randomized studies.

OBJECTIVES: We compared the risk of stent thrombosis (ST) after drug-eluting stents (DES) versus bare-metal stents (BMS), and tested the hypothesis that the risk of DES thrombosis is related to stent length. BACKGROUND: Whether DES increase the risk of ST remains unclear. Given the very low restenosis rate after drug-eluting stenting, longer stents are frequently implanted for the same lesion length in comparison to BMS. METHODS: We included in a meta-analysis 10 randomized studies comparing DES and BMS. Overall, 5,030 patients were included (2,602 were allocated to DES and 2,428 to BMS). The risk of thrombosis after DES versus BMS was compared, and the relationship between the rate of DES thrombosis and stent length was evaluated. RESULTS: Incidence of ST was not increased in patients receiving DES (0.58% vs. 0.54% for BMS; odds ratio: 1.05; 95% confidence interval [CI]: 0.51 to 2.15; p = 1.000). The overall rate of ST did not differ significantly between patients receiving sirolimus- or paclitaxel-eluting stents (0.57% vs. 0.58%; p = 1.000). We found a significant relation between the rate of ST and the stented length (Y = -1.455 + 0.121 X; 95% CI for beta: 0.014 to 0.227; R = 0.716; p = 0.031). In patients with DES, mean stented length was longer in those suffering ST (23.4 +/- 8.1 mm vs. 21.3 +/- 4.1 mm, p = 0.025). CONCLUSIONS: Drug-eluting stents do not increase the risk of ST, at least under appropriate anti-platelet therapy. The risk of ST after DES implantation is related to stent length.

Influence of aspirin resistance on platelet function profiles in patients on long-term aspirin and clopidogrel after percutaneous coronary intervention.

Increased platelet inhibition is achieved when clopidogrel is added to aspirin (acetylsalicylic acid [ASA]). A broad variability in platelet inhibition profiles during the early phases of treatment has been demonstrated and may be attributed to ASA resistance. However, the influence of ASA sensitivity on platelet function profiles of patients on long-term dual antiplatelet therapy has yet to be explored. A total of 135 patients who had previously undergone percutaneous coronary intervention on long-term (>1 month) ASA and clopidogrel therapy was included. The PFA-100 system was used to define ASA resistance. Platelet aggregation, after adenosine diphosphate (6 and 20 micromol/L) and collagen (6 microg/ml) stimuli, and platelet activation (glycoprotein IIb/IIIa activation and P-selectin expression), after adenosine diphosphate (2 micromol/L) and thrombin receptor-activating peptide (50 micromol/L) stimuli, were assessed by light transmittance aggregometry and flow cytometry, respectively. Patient variability in response to treatment was defined by the coefficient of variability. ASA resistance was found in 60 of 135 patients (44%). Patients with diabetes were more frequently ASA resistant. Collagen/epinephrine- and collagen/adenosine diphosphate-coated cartridges on the PFA-100 had shorter closure times in the ASA-resistant population compared with ASA-sensitive patients. Platelet aggregation and activation were significantly higher in ASA-resistant patients. A broad variability (coefficient of variation >0.25) in patient response to treatment was observed in ASA-resistant and -sensitive patients. In conclusion, ASA resistance is associated with increased platelet reactivity in patients on long-term dual antiplatelet treatment.

Influence of the CD14 C260T promoter polymorphism on C-reactive protein levels in patients with coronary artery disease.

The CD14 receptor is an important mediator of inflammatory reactions, and its expression is under genetic control. The allelic variant of the C260T polymorphism located in the promoter region of the CD14 gene is associated with receptor expression and ischemic risk. To date, most studies assessing the functional implications of the C260T polymorphism have been performed under proinflammatory conditions (e.g., acute coronary syndromes), and whether gene sequence variations of the CD14 receptor have any functional effect on systemic inflammation in patients in a stable phase of their atherosclerotic disease process is unknown. Eighty-two patients with stable coronary artery disease were studied. High-sensitivity C-reactive protein (hs-CRP) was used as a measurement of systemic inflammation. The genotype distribution of the C260T polymorphism of the CD14 gene was as follows: CC in 18 of 82 patients (22%), TC in 48 of 82 patients (58.5%), and TT in 16 of 82 patients (19.5%). TT subjects had increased hs-CRP levels compared with carriers of the C allele (p = 0.04). A higher percentage of T allele homozygotes had hs-CRP levels >0.3 mg/dl (p = 0.01). Homozygosis status of the T allele was independently associated with hs-CRP levels >0.3 mg/dl (p = 0.004). In conclusion, these observations may support the findings in large-scale studies that T homozygotes of this functional polymorphism are at increased ischemic risk.

[Efficacy of sirolimus-eluting stent implantation in diabetic patients with very small vessels (< or = 2.25 mm). Insights from the DIABETES trial]. / Eficacia de la implantación del stent recubierto de rapamicina en pacientes diabéticos con vasos muy pequeños (< or = 2.25 mm). Subanálisis del estudio DIABETES.

INTRODUCTION AND OBJECTIVES: Diabetic patients frequently have small-diameter vessels, which increases their risk of restenosis. The aim of this study was to determine the efficacy of sirolimus-eluting stent implantation in these high-risk patients following percutaneous coronary intervention. METHODS: Our study population comprised a subset of 85 diabetic patients from the DIABETES (DIABETes and sirolimus Eluting Stent) trial who had very small vessels, defined as those with a reference diameter < or =2.25 mm. In the 100 lesions treated, 49 sirolimus-eluting stents and 51 bare-metal stents were used. Glycoprotein IIb/IIIa inhibitors were used as recommended by the protocol and dual antiplatelet therapy was administered for 1 year. RESULTS: Baseline clinical and angiographic characteristics were comparable in the two groups. The patients' mean age was 66 (9) years, 42% were women, and 37% were insulin-dependent. On average, the lesion length was 15.0 (9.0) mm and the reference diameter was 1.9 (0.2) mm. At 9-month follow-up, both late lumen loss and the restenosis rate were significantly lower in the sirolimus-eluting stent group than in the bare-metal stent group, at -0.03 (0.3) mm vs 0.44 (0.5) mm (P< .001), and 9.1% vs 39.1% (P=.001), respectively. These differences were also observed in the subgroup of insulin-dependent patients. At 1-year follow-up, the stent thrombosis rate was 0% in the sirolimus-eluting stent group, whereas two patients in the bare-metal stent group presented with stent thrombosis. CONCLUSIONS: Sirolimus-eluting stent implantation in diabetics with very small vessels is safe and effective, even in insulin-dependent patients.

Transient left ventricular apical ballooning.

We describe the case of an elderly woman patient referred for primary angioplasty for acute anterior myocardial infarction, which developed after intense emotional stress. The coronary angiogram was surprisingly normal, but left ventriculography showed severe apical dilatation and dyskinesia, confirmed by echocardiography. By this time we suspected a syndrome of transient apical ballooning without coronary stenosis, which mimics acute myocardial infarction. She underwent medical therapy and subsequent clinical evolution was favorable, with complete recovery of left ventricular systolic function. We discuss the clinical setting and the pathophysiologic mechanisms of this syndrome.

Clinical variables related with in-stent restenosis late regression after bare metal coronary stenting.

UNLABELLED: In-stent restenosis (ISR) has an incidence between 20% and 30% using bare metal stents. ISR late regression phenomenon (ISRLR) has been previously described, but clinical variables related with this phenomenon remain unclear. The aim of the study was to identify the variables related with ISRLR. METHODS: We identified from our data base 30 patients between November 1995 and September 2002 that fulfilled the following criteria: 1) Documented ISR at follow-up angiography (CA-1); 2) treated medically; and 3) Referred for a second follow-up angiography (CA-2). at least 3 months after CA-1. ISRLR was defined as a > 0.2 mm increase in MLD between CA-1 and CA-2, calculated as the 2-fold of our inter-observer variability. ISR late progression was defined as a > 0.2 mm decrease in minimum lumen diameter (MLD) between CA-1 and CA-2. RESULTS: At the time of CA-2 only 2 patients (6.7%) had symptoms related with the previously stented vessel. We found a mean MLD of 1.03+/-0.34 mm and 1.54+/-0.48 mm at CA-1 and CA-2 respectively (AMLD = 0.51 +/-0.34 mm; p < 0.001). Twenty four patients (80.0%) had ISRLR. Two variables were related to the presence or absence ISRLR: Current smoking at the time of coronary stenting (70.8% vs 20.0% respectively, p = 0.026) and acute coronary syndrome as clinical indication for coronary stenting (and 83.5% vs 40.0% respectively, p = 0.029). CONCLUSION: ISRLR is a frequent phenomenon in patients with ISR treated medically, probably contributing to the benign long-term clinical outcome that has been previously described in patients with asymptomatic or mildly symptomatic ISR. Current smoking at the time of coronary stenting and acute coronary syndrome as clinical indication for coronary stenting are associated with this phenomenon.

Coronary stenting versus balloon angioplasty in small vessels: a meta-analysis from 11 randomized studies.

OBJECTIVES: A meta-analysis of 11 randomized trials was done to compare stenting versus balloon angioplasty (BA) in small coronary vessels. BACKGROUND: Randomized studies on coronary stenting (CS) in small vessels have yielded controversial results. METHODS: Eleven randomized trials on CS versus BA in small vessels, including angiographic re-evaluation at six months, were analyzed. RESULTS: The BeStent (Medtronic Instent, Minneapolis, Minnesota) was used in four studies, the Multi-Link (Guidant, Advanced Cardiovascular Systems Inc., Santa Clara, California) in three trials, and the NIR (Boston Scientific Corp., Boston, Massachusetts), JoStent (Jomed International AB, Helsingborg, Sweden), Tenax (Biotronik, Berlin, Germany), and BioDivysio (Abbott Vascular Devices, Redwood City, California) in the remaining four trials. Overall, 3,541 patients were included (1,672 allocated to BA and 1,869 to stent). The rate of cross-over from balloon to stent in the pooled population was 19%, and unsuccessful stent deployment occurred in 2% of the patients allocated to stent. The pooled rates of restenosis were 25.8% and 34.2% in patients allocated to stent and balloon, respectively (p = 0.003) (risk ratio [RR] 0.77; 95% confidence interval [CI] 0.65 to 0.92). A smaller reference vessel diameter at baseline was associated with a higher risk reduction in the restenosis rate (y = -3.551 + 1.826 [x]; p = 0.012). Patients allocated to stent had lower rates of major adverse cardiac events (15.0% vs. 21.8%, p = 0.002; RR 0.70; 95% CI 0.57 to 0.87) and new target vessel revascularizations (12.5% vs. 17.0%, p = 0.004; RR 0.75, 95% CI 0.61 to 0.91). CONCLUSIONS: Elective stenting is superior to provisional stenting in small coronary arteries. This benefit is more evident in smaller coronary arteries.

Importance of diastolic fractional flow reserve and dobutamine challenge in physiologic assessment of myocardial bridging.

OBJECTIVES: This study reports a comparative assessment of the hemodynamic relevance of myocardial bridges (MB) using two modalities of fractional flow reserve (FFR), with and without concomitant inotropic challenge. BACKGROUND: Extravascular coronary compression by means of MB is modulated by myocardial inotropism and causes intracoronary systolic pressure overshooting and negative systolic gradients across the MB. The former characteristic suggests that adequate hemodynamic assessment of MB should include inotropic stimulation. The latter characteristic might interfere with FFR by decreasing the mean pressure gradient. METHODS: We compared the hemodynamic relevance of 12 lone MB in symptomatic patients using conventional (mean) and diastolic FFR. Diastolic FFR was obtained from post-processed, digitally acquired electrocardiogram and pressure signals. Previously validated cut off values of 0.75 (mean FFR) and 0.76 (diastolic FFR) for hemodynamic relevance were used. Measurements were performed at baseline and after incremental intravenous dobutamine doses. RESULTS: Fractional flow reserve decreased during dobutamine challenge: mean FFR was 0.90 +/- 0.04 at baseline and 0.84 +/- 0.06 after dobutamine (p = 0.0008); similarly, diastolic FFR was 0.88 +/- 0.05 and 0.77 +/- 0.10 before and after dobutamine, respectively (p = 0.0006). Diastolic FFR identified hemodynamic relevance in five patients, whereas mean FFR did so in only one patient. The discrepancy between mean FFR and diastolic FFR increased with dobutamine challenge: the ratio of mean FFR/diastolic FFR was 1.03 at baseline and 1.09 after dobutamine (p = 0.02). During the administration of dobutamine, the discrepancy was inversely related to the systolic pressure gradient (r = 0.58, P = 0.04). CONCLUSIONS: Physiologic assessment of MB should include dobutamine challenge. Because the overshooting of systolic pressure interferes with and is a cause of error in FFR measurements based on mean pressures, diastolic FFR appears to be the technique of choice for MB assessment, whereas mean FFR should be used with caution.

Intracoronary brachytherapy after stenting de novo lesions in diabetic patients: results of a randomized intravascular ultrasound study.

OBJECTIVES: We studied the efficacy of intracoronary brachytherapy (ICB) after successful coronary stenting in diabetic patients with de novo lesions. BACKGROUND: Intracoronary brachytherapy has proven effective in preventing recurrences in patients with in-stent restenosis. However, the role of ICB for the treatment of de novo coronary stenoses remains controversial. METHODS: Ninety-two patients were randomized to either ICB or no radiation after stenting. Primary end points were in-stent mean neointimal area (primary end point of efficacy) and minimal luminal area of the entire vessel segment (primary end point of effectiveness), as assessed by intravascular ultrasound at six-month follow-up. Quantitative coronary angiography analysis was performed at the target, injured, irradiated, and entire vessel segments. RESULTS: At follow-up, the in-stent mean neointimal area was 52% smaller in the ICB group (p < 0.0001). However, there was no difference in the minimal luminal area of the vessel segment (4.5 +/- 2.4 mm2 vs. 4.4 +/- 2.1 mm2). Restenosis rates increased progressively by the analyzed segment in the ICB group: target (7.1% vs. 20.9%, p = 0.07), injured (9.5% vs. 20.9%, p = NS), irradiated (14.3% vs. 20.9%, p = NS), and vessel segment (23.8% vs. 25.6%, p = NS). At one year, 1 cardiac death, 6 myocardial infarctions (MIs) (3 due to late stent thrombosis), and 10 target vessel revascularizations (TVRs) (6 due to the edge effect) occurred in the ICB group, whereas in the nonradiation group, there were 11 TVRs and no deaths or MIs. CONCLUSIONS: Intracoronary brachytherapy significantly inhibited in-stent neointimal hyperplasia after stenting in diabetic patients. However, clinically this was counteracted by the occurrence of the edge effect and late stent thrombosis.