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.

Low coronary microcirculatory resistance associated with profound hypotension during intravenous adenosine infusion: implications for the functional assessment of coronary stenoses.

BACKGROUND: Intravenous adenosine infusion produces coronary and systemic vasodilatation, generally leading to systemic hypotension. However, adenosine-induced hypotension during stable hyperemia is heterogeneous, and its relevance to coronary stenoses assessment with fractional flow reserve (FFR) remains largely unknown. METHODS AND RESULTS: FFR, coronary flow reserve, and index of microcirculatory resistance were measured in 93 stenosed arteries (79 patients). Clinical and intracoronary measurements were analyzed among tertiles of the percentage degree of adenosine-induced hypotension, defined as follows: %ΔP(a)=-[100-(hyperemic aortic pressure×100/baseline aortic pressure)]. Overall, %ΔP(a) was -13.6±12.0%. Body mass index was associated with %ΔP(a) (r=0.258; P=0.025) and obesity, an independent predictor of profound adenosine-induced hypotension (tertile 3 of %ΔP(a); odds ratio, 3.95 [95% confidence interval, 1.48-10.54]; P=0.006). %ΔP(a) was associated with index of microcirculatory resistance (ρ=0.311; P=0.002), coronary flow reserve (r=-0.246; P=0.017), and marginally with FFR (r=0.203; P=0.051). However, index of microcirculatory resistance (ß=0.003; P<0.001) and not %ΔP(a) (ß=-0.001; P=0.564) was a predictor of FFR. Compared with tertiles 1 and 2 of %ΔP(a) (n=62 [66.6%]), stenoses assessed during profound adenosine-induced hypotension (n=31 [33.3%]) had lower index of microcirculatory resistance (12.4 [8.6-22.7] versus 20 [15.8-35.5]; P=0.001) and FFR values (0.77±0.13 versus 0.83±0.12; P=0.021), as well as a nonsignificant increase in coronary flow reserve (2.5±1.1 versus 2.2±0.87; P=0.170). CONCLUSIONS: The modification of systemic blood pressure during intravenous adenosine infusion is related to hyperemic microcirculatory resistance in the heart. Profound adenosine-induced hypotension is associated with obesity, lower coronary microcirculatory resistance, and lower FFR values.

Spontaneous coronary artery dissection: long-term follow-up of a large series of patients prospectively managed with a "conservative" therapeutic strategy.

OBJECTIVES: This study sought to assess the long-term clinical outcome of patients with spontaneous coronary artery dissection (SCD) managed with a conservative strategy. BACKGROUND: SCD is a rare, but challenging, clinical entity. METHODS: A prospective protocol, including a conservative management strategy, was followed. Revascularization was only considered in cases with ongoing/recurrent ischemia. Inflammatory/immunologic markers were systematically obtained. RESULTS: Forty-five consecutive patients (incidence 0.27%) were studied during a 6-year period. Of these, 27 patients (60%) had "isolated" SCD (I-SCD), and 18 had SCD associated with coronary artery disease (A-SCD). Age was 53 ± 11 years, and 26 patients were female. Most patients presented with an acute myocardial infarction. SCD had a diffuse angiographic pattern (length: 31 ± 23 mm). In 11 patients, the diagnosis was confirmed by intracoronary imaging techniques. Sixteen patients (35%) required revascularization during initial admission. One patient died after surgery, but no additional patient experienced recurrent myocardial infarction. No significant inflammatory/immunologic abnormalities were detected. At follow-up (median 730 days), only 3 patients presented with adverse events (1 died of congestive heart failure, and 2 required revascularization). No patient experienced a myocardial infarction or died suddenly. Event-free survival was similar (94% and 88%, respectively) in patients with I-SCD and A-SCD. Notably, at angiographic follow-up, spontaneous "disappearance" of the SCD image was found in 7 of 13 (54%) patients. CONCLUSIONS: In this large prospective series of consecutive patients with SCD, a "conservative" therapeutic strategy provided excellent long-term prognosis. Clinical outcome was similar in patients with I-SCD and A-SCD. The natural history of SCD includes spontaneous healing with complete resolution.

End-stage heart disease in the elderly.

This document was produced by the Spanish Society of Cardiology Section on Geriatric Cardiology "End-stage heart disease in the elderly" working group. Its aim was to provide an expert overview that would increase understanding of the last days of life of elderly patients with heart disease and improve treatment and clinical decision-making. As elderly heart disease patients form a heterogeneous group, thorough clinical evaluation is essential, in particular to identify factors that could influence prognosis (e.g., heart disease, comorbid conditions, functional status and frailty). The evaluation should be carried out before any clinical decisions are made, especially those that could restrict therapy, such as do-not-resuscitate orders or instructions to deactivate an implantable cardioverter-defibrillator. Elderly patients with terminal heart disease have the right to expect a certain level of care and consideration: they should not suffer unnecessarily, their freely expressed wishes should be respected, they should be fully informed about their medical condition, they should be able to express an opinion about possible interventions, and they should be entitled to receive psychospiritual care. After an incurable disease has been diagnosed, the aim of palliative care should be to control symptoms. It should not be used only when the patient is close to death. Although palliative care is relatively undeveloped in heart disease, its use must be borne in mind in elderly patients with advanced heart failure. The main aims are to make the patient as comfortable as possible in all senses and to optimize quality of life in the patient's final days, while avoiding the use of aggressive treatments that consume health-care resources without providing any benefits.

Long-term clinical benefit of sirolimus-eluting stents in patients with in-stent restenosis results of the RIBS-II (Restenosis Intra-stent: Balloon angioplasty vs. elective sirolimus-eluting Stenting) study.

OBJECTIVES: We sought to assess the long-term effectiveness and safety of sirolimus-eluting stents (SES) in patients with in-stent restenosis (ISR). BACKGROUND: Treatment of patients with ISR remains a challenge. The long-term outcome of patients with ISR treated with SES remains unknown. METHODS: The RIBS-II (Restenosis Intra-stent: Balloon angioplasty vs. elective sirolimus-eluting Stenting) study was a randomized trial conducted in 150 patients with ISR (76 SES, 74 balloon angioplasty [BA]). The long-term (>1 year) clinical outcome and pre-specified subgroup analyses were pre-defined secondary study end points. RESULTS: At 1 year, the event-free survival (death, myocardial infarction, target vessel revascularization [TVR]) was better in the SES group (88% vs. 69%, p < 0.005). Additional long-term (>3 years) clinical follow-up was obtained in 97% of patients (median 3.3 years). After the first year, 3 patients died (1 SES, 2 BA), 5 suffered myocardial infarction (4 SES, 1 BA), and 7 required TVR (4 SES, 3 BA). At last follow-up, definitive/probable/possible stent thrombosis was similar in both groups (2/2/1 SES vs. 1/0/3 BA, p = NS). At 4 years, the event-free survival was 76% in the SES arm and 65% in the BA arm (p = 0.019). On multivariate analysis, SES implantation was an independent predictor of event-free survival. Subgroup analyses were consistent with the main outcome measure. CONCLUSIONS: In patients with ISR, SES implantation remains effective and safe at very long-term clinical follow-up.

Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease.

OBJECTIVES: This study sought to determine the prognostic implications of high platelet reactivity (HPR) assessed in type 2 diabetes mellitus (T2DM) patients while in their steady-state phase of dual antiplatelet therapy. BACKGROUND: Type 2 diabetes mellitus patients have increased platelet reactivity compared with nondiabetic patients. Whether HPR assessed in T2DM while in their steady-state phase of dual antiplatelet therapy is associated with an increased risk of major adverse cardiovascular events (MACE) is unknown. METHODS: Platelet function analyses, which included measures of platelet aggregation and activation, were performed in 173 T2DM patients with coronary artery disease on chronic treatment with aspirin and clopidogrel. The HPR was defined as the upper quartile of maximal platelet aggregation (Agg(max)) after 20 micromol/l adenosine diphosphate stimuli. Patients were followed up for 2 years and MACE were recorded. RESULTS: A total of 41 MACE occurred in 34 patients (19.7%) during the 2-year follow-up. The MACE occurred in 15.2%, 12.2%, 12.2%, and 37.7% of patients from the lowest to upper quartile, respectively (p = 0.005). The HPR was the strongest independent predictor of MACE (hazard ratio 3.35, 95% confidence interval [CI] 1.68 to 6.66, p = 0.001). Receiver-operating characteristic analysis indicated that a cutoff value of 62% Agg(max) best predicted MACE (37.8% vs. 13.2%, odds ratio 3.96, 95% CI 1.8 to 8.7, p < 0.001). Patients with HPR had up-regulation of multiple platelet signaling pathways (p < 0.0001 for all assays), indicative of a global hyperreactive platelet status. CONCLUSIONS: High platelet reactivity determined in T2DM patients with coronary artery disease while on chronic dual antiplatelet therapy is associated with a higher risk of long-term adverse cardiovascular events, suggesting the need for tailored antithrombotic drug regimens in these high-risk patients.

Long-term clinical benefit of sirolimus-eluting stent implantation in diabetic patients with de novo coronary stenoses: long-term results of the DIABETES trial.

AIMS: Sirolimus stent implantation has been demonstrated to be safe and effective in diabetics; however, the long-term outcomes in this high-risk population remain unknown. The aim of this study was to determine the long-term safety and efficacy of the sirolimus-eluting stent (SES) when compared with the bare metal stent (BMS) in patients included in the DIABETES (DIABETes and sirolimus Eluting Stent) trial. METHODS AND RESULTS: The prospective multicentre DIABETES trial randomized 160 diabetic patients with one or more significant coronary stenoses in one, two, or three vessels to either SES or BMS implantation. One-year dual antiplatelet therapy (aspirin plus clopidogrel) was routinely prescribed. Clinical follow-up was scheduled at 1, 9, 12, and 13 months and 2 years. Baseline clinical and angiographic characteristics were comparable between groups. At 2 years, the rate of target lesion revascularization was significantly lower in the SES group compared with the BMS group (7.7 vs. 35.0%, P < 0.001). However, the total revascularization rate at 2 years increased in both groups due to progression of atherosclerosis in coronary segments remote from the target lesion (rate of atherosclerosis progression: 7.7% in SES group vs. 10% in BMS group; P = 0.7). During dual antiplatelet treatment (1 year), there was no stent thrombosis in the SES group, whereas two patients presented it in the BMS group. However, after clopidogrel withdrawal, three patients allocated to the SES group presented stent thromboses vs. none in the BMS group. CONCLUSION: SES implantation in diabetic patients remains effective at 2-year follow-up. However, clinical efficacy appeared to be reduced by the occurrence of stent thrombosis between 1 and 2 years.

Revascularização da descendente anterior proximal com stents revestidos por fármacos / Proximal left anterior descending coronary artery revascularization with drug-eluting stents

OBJETIVO: Avaliar o prognóstico clínico dos doentes coronários submetidos a revascularização percutânea com implantação de stents revestidos com fármacos na descendente anterior proximal. MÉTODOS: Cento e setenta doentes consecutivos, com idade média de 65 anos, 49 (29 por cento) mulheres, receberam implante de pelo menos um stent revestido com fármaco, no nosso centro. O número total de stents revestidos com fármaco implantados foi 189, dos quais 115 (61 por cento) de sirolimus (CYPHER®) e 74 (39 por cento) de paclitaxel (TAXUS®). Em 100 (60 por cento) dos casos, estava presente doença coronário multivaso. Em 61 (36 por cento) dos doentes tratou-se outro segmento coronário para além da descendente anterior proximal. Efetuou-se um seguimento clínico durante um tempo médio de 11 ± 5 meses e controle angiográfico entre os seis e os nove meses. Obteve-se um endpoint final composto por morte, infarto agudo do miocárdio e pela necessidade de reintervenção sobre a descendente anterior. Analisou-se secundariamente a ocorrência de reestenose, a necessidade de reintervenção sobre o segmento proximal da descendente anterior e a trombose de stent. RESULTADOS: O procedimento teve êxito angiográfico imediato em todos os doentes. Registraram-se duas mortes, dois infartos agudos do miocárdio, e duas reintervenções coronárias percutâneas por trombose de stent no período intra-hospitalar. Aos seis meses de seguimento, observou-se mais uma morte cardíaca e identificaram-se três infartos do miocárdio; houve necessidade de três novos procedimentos de revascularização. Até ao final do seguimento, verificaram-se mais três mortes, três infartos do miocárdio e oito revascularizações da descendente anterior, duas delas por cirurgia. A sobrevivência livre de eventos cardíacos adversos maior foi de 91 por cento. A mortalidade cardíaca foi de 3 por cento. A reestenose binária no segmento proximal da descendente anterior foi de 4,1 por cento. A sobrevivência livre...

OBJECTIVE: To assess the clinical prognosis of patients with coronary artery diseases undergoing percutaneous revascularization with drug-eluting stent implantation in the proximal left anterior descending coronary artery. METHODS: One hundred and seventy consecutive patients with mean age of 65 years, 49 of them females (29 percent), undergoing implantation of at least one drug-eluting stent in our medical center. The total number of drug-eluting stents implanted was 189, of which 115 (61 percent) were sirolimus-eluting (CYPHER TM) and 74 (39 percent) were paclitaxel-eluting stents (TAXUS TM). In 100 (60 percent) of the cases, multivessel coronary artery disease was present. In 61 (36 percent) patients another coronary artery segment was treated in addition to the proximal left anterior descending coronary artery. The mean clinical follow-up period was 11 ± 5 months, and angiographic controls were performed between 6 and 9 months. The final endpoint was a composite of death, acute myocardial infarction and need for reintervention on the anterior descending. The secondary endpoint included the occurrence of restenosis, need for reintervention on the proximal segment of the left anterior descending and stent thrombosis. RESULTS: The procedure achieved immediate angiographic success in all patients. Two deaths, two acute myocardial infarctions, and two percutaneous coronary reinterventions due to stent thrombosis were recorded during in-hospital stay. At the sixth month of follow-up, an additional cardiac death and three myocardial infarctions were observed; three repeat revascularization procedures were required. Up to the end of the follow-up, three additional deaths, three myocardial infarctions and eight revascularization procedures of the anterior descending, two of them surgical, were verified. Survival free from major adverse cardiac events was 91 percent. Cardiac mortality was 3 percent. Binary restenosis in the proximal segment...

Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment.

OBJECTIVES: This study sought to assess the influence of type 2 diabetes mellitus (T2DM) and the impact of hypoglycemic treatment (insulin vs. noninsulin) on platelet function profiles in patients treated with dual oral antiplatelet therapy. BACKGROUND: Insulin inhibits platelet aggregation by suppressing the P2Y12 pathway. However, T2DM patients have a loss of responsiveness to insulin that leads to upregulation of the P2Y12 pathway, increased platelet reactivity, and reduced responsiveness to antiplatelet agents. Patients with insulin-treated diabetes mellitus (ITDM) have a more advanced disease status and higher atherothrombotic risk compared with non-ITDM (NITDM). However, the impact of insulin therapy on platelet dysfunction in patients treated with P2Y12 antagonists is unknown. METHODS: A total of 201 T2DM and 65 nondiabetic patients with coronary artery disease in a steady phase of aspirin and clopidogrel treatment were studied. Platelet aggregation was assessed using agonists specific (6 and 20 microM adenosine diphosphate [ADP]) and nonspecific (6 microg/ml collagen and 20 microM epinephrine) for the P2Y12 pathway. High shear-induced platelet reactivity was assessed by means of the PFA-100 system (Dade-Behring International, Miami, Florida). RESULTS: The T2DM patients had platelet aggregation and shear-induced platelet function significantly increased compared with nondiabetic patients using all assays. Platelet aggregation was increased in ITDM (n = 68) compared with NITDM (n = 133) patients after P2Y12-specific stimuli. Insulin treatment was the strongest predictor of ADP-induced aggregation. Platelet function profiles were similar between ITDM and NITDM using assays nonspecific to the P2Y12 pathway. Platelet dysfunction was independent of glycemic control and inflammatory status. CONCLUSIONS: The P2Y12-dependent and -independent pathways of platelet reactivity are altered in T2DM compared with nondiabetic patients, and ITDM have greater ADP-induced platelet aggregation compared with NITDM.

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.

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.

Variability in platelet aggregation following sustained aspirin and clopidogrel treatment in patients with coronary heart disease and influence of the 807 C/T polymorphism of the glycoprotein Ia gene.

A broad variability in patient response to dual antiplatelet treatment has been described during the first month of treatment. Data on platelet function profiles in patients on dual antiplatelet therapy for a more sustained period are limited. Whether gene sequence variations of the glycoprotein Ia/IIa receptor influence platelet aggregation in these patients is also unknown. The aim of this study was to characterize platelet aggregation profiles in patients on dual antiplatelet treatment (aspirin plus clopidogrel) for >1 month and to assess whether these may be influenced by the C807T polymorphism of the glycoprotein Ia gene. We included 82 patients, who were divided into 2 groups: carriers (CT + TT genotypes; n = 51) and noncarriers (CC genotype; n = 31) of the mutant T allele. Platelet aggregation was assessed using light transmittance aggregometry after stimuli with adenosine diphosphate (20 micromol/L), collagen (6 microg/ml), and epinephrine (20 micromol/L). A significant variability in the distribution of platelet aggregation was observed in the overall study population, as well as in carriers and noncarriers of the T allele. T allele carriers had increased platelet aggregation compared with noncarriers after stimuli with adenosine diphosphate, collagen, and epinephrine (p <0.05 for all platelet aggregation assays). Thus, platelet aggregation varied significantly in patients on long-term dual antiplatelet treatment and was increased in T allele carriers of the 807C/T polymorphism of the glycoprotein Ia gene. These findings may contribute to the increased ischemic risk observed in these patients.

Compromiso de vasos secundarios durante la implantación directa de stent coronario: Incidencia y factores relacionados / Side branch occlusion during direct stent implantation: Incidence and related factors

Objetivo: El objetivo fue evaluar el grado de compromiso de las ramas que son enjauladas durante la implantación directa de stent. Pacientes y métodos: Se estudiaron 56 pacientes en los que se implantó al menos un stent coronario (58 stents) sin dilatación previa con balón y en los que se enjauló alguna rama secundaria. Se evaluó la tasa de pérdida de la rama, el efecto de la implantación del stent sobre el flujo de esta rama y los factores relacionados con estos hechos. Resultados: El vaso principal fue la descendente anterior en el 63%, la circunfleja en el 21%, la coronaria derecha en el 14% y el tronco principal de la coronaria izquierda en un caso. Se obtuvo éxito angiográfico sobre el vaso principal en todos los casos. Antes del procedimiento, el flujo a nivel de la rama secundaria era TIMI grado 3, 2 y 0 en 55 (95%), 2 (3%) y un caso (2%), respectivamente. Tras la implantación del stent, el flujo era TIMI grado 3, 2, 1 y 0 en 50 (86%), 1 (2%), 2 (3%) y 5 (9%) casos, respectivamente (p = 0.204). La incidencia de pérdida de la rama fue 12% (7/58); en un caso, se intentó con éxito recanalizar y dilatar ésta a través de los struts del stent, por lo que la tasa de pérdida de rama final fue 10% (6/ 58). Las ramas que se ocluyeron tenían un mayor grado de estenosis en el origen antes de la implantación del stent (30.2 ± 31.3% vs 16.8 ± 11.1%, p = 0.028). En los pacientes que se reevaluaron angiográficamente, a los 6.2 ±1.9 meses, el 50% de las ramas que se habían ocluido se encontraban permeables, y el 88% de las que no se comprometieron seguían permeables. Conclusiones: La tasa de oclusión de las ramas con la implantación directa de stent fue 12% en nuestra serie, cifra similar a la que ocurre con la implantación de stent tras dilatación con balón. Por tanto, la existencia de ramas localizadas en el segmento en el que va a implantarse el stent no tiene por qué condicionar la decisión o no de realizar una dilatación previa con balón.

Aim: The aim of the study was to evaluate the compromise of side branches when jailed by a coronary stent implanted without balloon predilation. Patients and methods: 56 patients in which at least a coronary stent was implanted without balloon predilation and covering a side brach (58 stents, 1.04 ± 0.19 per patient) were studied. The effect of direct coronary stent implantation over side branch flow, as well as the characteristics associated were studied. Results: The main vessel was left anterior descending in 63%, left circumflex in 21%, right coronary in 14%, and left main in one case. An angiographic successful result in the main vessel was obtained in all cases. Coronary flow was TIMI 3, 2, 1, and 0 in 95%, 3%, 0%, and 2% before the procedure, in comparison with 86%, 2%, 3%, and 9% after stent implantation (p = 0.204). The incidence of side branch occlusion was 12% (7/58). In one case, the side branch was dilated across the stent struts, and thus the rate of side branch loss at the end of the procedure was 10% (6/58). In cases of side branch occlusion, there was a more severe stenosis at its origin before stent implantation (30.2 ± 31.3% vs 16.8± 11.1%, p = 0.028). Fifty percent of side branches occluded after direct coronary stent implantation and angiographically reevaluated at follow-up became patent, and 88% of side branches not affected after stent implantation remained patent at 6.2 ± 1.9 months. Conclusion: The rate of side branch occlusion after direct stent implantation in our series was 12%, that is not different from that reported for conventional stent implantation. Thus, the decision of using direct or conventional coronary stenting should not be conditioned by the presence of side branches arising from the target lesion.

Long-term outcome of patients with proximal left anterior descending coronary artery in-stent restenosis treated with a second percutaneous procedure.

Patients with in-stent restenosis involving the proximal segment of the left anterior descending coronary artery are frequently sent for surgical revascularization. We studied the long-term (3.3 +/- 2.8 years) outcome of 123 patients with in-stent restenosis involving the proximal left anterior descending coronary artery who were treated with a second percutaneous procedure. Cumulative survival rate, probability of being alive and free from surgical revascularization, and probability of being alive and free from new revascularization procedures was 98.3 +/- 1.2%, 92.8 +/- 2.5%, and 82.2 +/- 3.6% at 1 year, and 95.2 +/- 2.5%, 88.5 +/- 3.4%, and 76.9 +/- 4.3% at 3 years, respectively. Thus, in patients with in-stent restenosis involving the proximal left anterior descending artery, a second percutaneous procedure is a feasible and safe long-term strategy, with few patients ultimately requiring surgical revascularization.

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.

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.

Multiple congenital coronary artery fistulae draining into the left ventricle.

Coronary artery fistula between a coronary artery and a cardiac chamber is a rare condition, especially when multiple fistulas communicate with the left ventricle. Herein we report a case of an elderly woman with multiple diffuse coronary artery-left ventricular fistulas diagnosed by angiography. Since the coronary artery-cardiac chamber communications were multiple and diffuse neither surgery nor transcatheter coil occlusion was considered in this case.

Is a 300 mg clopidogrel loading dose sufficient to inhibit platelet function early after coronary stenting? A platelet function profile study.

BACKGROUND: Clopidogrel combined to aspirin reduces the early risk of stent thrombosis and a clopidogrel pre-treatment strategy is associated with a better outcome. However, in clinical practice such pre-treatment strategy is not always feasible and clopidogrel is frequently not administered until the time of intervention. Aim of the study was to compare platelet function profiles in patients undergoing coronary stenting receiving clopidogrel pre-treatment (75 mg x 2 daily at least 48 hours before intervention) compared to that of patients receiving a 300 mg loading dose at intervention time. METHODS: A total of 50 patients were included in whom patients' platelet aggregation (using light transmittance aggregometry) and platelet activation (P-selectin and PAC-1 expression by whole blood flow cytometry) were assessed following ADP stimuli at baseline, and 4 hours and 24 hours following coronary stenting. RESULTS: In the overall study population, 16/50 (32%) patients were pre-treated with clopidogrel and 34/50 (68%) received clopidogrel loading dose at intervention time. Platelet aggregation, as well as P-selectin and PAC-1 expression were significantly lower in clopidogrel pre-treated patients at baseline (p<0.001) and at 4 hours (p<0.01), while they were similarly inhibited 24 hours after intervention. In conclusion, platelet reactivity of patients treated with clopidogrel front loading at intervention time remains significantly higher than that of pre-treated patients in the early hours after coronary stenting. A higher loading dose at intervention time may be warranted to overcome the early risk of thrombotic complications.