Percutaneous coronary intervention in small-caliber arteries

Background: Percutaneous coronary intervention (PCI) in small-caliber arteries corresponds to 30 to 40% of invasive therapeutic procedures and shows high and persistent rates of restenosis, despite the evolution of the devices used. The objective of this study was to evaluate changes in patient outcomes associated with the evolution of this therapeutic modality in Brazil during the last 10 years. Methods: A total of 24,895 patients from the National Center for Cardiovascular Interventions (CENIC) registry were included. These patients were subjected to 25,892 procedures with at least one stent with a diameter ≤ 2.5 mm between 2006 and 2016, which was subdivided into three periods: 2006-2008, 2009-2011 and 2012-2016. The clinical, angiographic and in-hospital outcomes of these patients were evaluated. Results: The mean age was 63.3 years. There was a predominance of male patients (59.7%), 26.1% had diabetes, and 59.7% had single-vessel coronary artery disease. The mean diameter of the stents used was 2.47 mm, and 25.5% were drug-eluting stents. Among the in-hospital outcomes, 140 deaths (0.6%), 79 myocardial infarctions (0.3%) and four emergency myocardial revascularization surgeries (0.02%) occurred. The prevalence of cardiovascular risk factors and the rate of serious adverse cardiac events decreased (1.2% vs. 0.6%; p < 0.0001) from the 2006-2008 to the 2012-2016 period. Conclusions: In patients undergoing percutaneous coronary intervention in small-caliber vessels registered in the CENIC, there was a favorable temporal evolution related to a decrease in risk factors and a lower rate of in-hospital complications, despite an increase in the complexity of the procedures. © 2017 Sociedade Brasileira de Hemodinâmica e Cardiologia Intervencionista. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Autor para correspondência: Hospital do Rim, Setor de Cardiologia e Cirurgia Cardiovascular, Rua Borges Lagoa, 960, Vila Clementino, CEP: 04038-002, São Paulo, SP, Brasil. E-mail: felipe.macedo.coelho@gmail.com (F.M. Coelho). A revisão por pares é de responsabilidade da Sociedade Brasileira de Hemodinâmica e Cardiologia Intervencionista. Intervenção coronária percutânea em artérias de fino calibre Felipe de Macedo Coelhoa,*, Apoana Gomes Florib, Marco Tulio de Souzab, Vladimir Ailton Cuma Nancassab, Flavius Augustus Maglianob, Jorge Luis Vivar Sanchesb, Sidney Ramos Borges Filhob, Erlon Oliveira de Abreu Silvaa, Rosley Weber Alvarenga Fernandesa a Hospital do Rim, São Paulo, SP, Brasil b Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil I N F O R M A Ç Õ E S S O B R E O A R T I G O Histórico do artigo: Recebido em 6 de fevereiro de 2017 Aceito em 21 de julho de 2017 Palavras-chave: Doença das coronárias Intervenção coronária percutânea Stents Sistema de registros 23 F. Coelho et al. / Rev Bras Cardiol Invasiva. 2017;25(1-4):22-26


Introduction
Percutaneous coronary intervention (PCI) in small-caliber arteries remains a challenge for Interventional Cardiology.2][3] The rates of adverse cardiac events remain high, particularly restenosis requiring a new revascularization, 4 despite the evolution of devices in recent decades-from balloon angioplasty to the use of drug-eluting stents-which was responsible for a significant reduction in the prevalence of this complication. 5,6he persistence of high rates of adverse clinical outcomes in this scenario makes it important to improve our knowledge of the concomitant clinical and angiographic characteristics observed in this population.In Brazil, studies on PCI in small-caliber arteries are scarce, involve a small number of patients and are limited to single-center experiences. 7,8This study aimed to evaluate the temporal profile of percutaneous procedures in small vessels performed in a more comprehensive national context in the last 10 years.

Methods
The National Center for Cardiovascular Interventions (Central Nacional de Intervenções Cardiovasculares -CENIC), belonging to the Brazilian Society of Hemodynamics and Interventional Cardiology (Sociedade Brasileira de Hemodinâmica e Cardiologia Intervencionista -SBHCI), is a clinical registry in which patients are voluntarily included by the society's members.The registry contains a list of procedures performed since 1992 and encompasses variables related to coronary, structural and congenital interventions.The data are collected prospectively and recorded in standardized electronic forms.The patients included in the present study were enrolled from this registry.The patients included had undergone procedures performed from June 2006 to March 2016 in which at least one stent of diameter ≤ 2.5 mm was used, totaling 25,892 PCIs.To compare the evolution of the procedures, the sample was divided into three periods: 2006-2008, 2009-2011 and 2012-2016.Small-caliber arteries with reference luminal diameter ≤ 2.5 mm were considered.The lesions were classified according to the definition of the American College of Cardiology/American Heart Association (ACC/AHA) modified by Ellis. 9For determination of coronary flow, the Thrombolysis in Myocardial Infarction (TIMI) score was used. 10Left ventricular function was assessed qualitatively by ventriculography and graded as normal, mild dysfunction, moderate dysfunction or severe dysfunction.Due to the large number of losses in this variable, we grouped ventricular dysfunction into a single dichotomous variable.
Procedure success was defined as obtaining residual stenosis < 30%, with final TIMI 3 flow and absence of in-hospital death, nonfatal acute myocardial infarction (AMI) and emergency coronary artery bypass graft surgery (CABG).Among the adverse cardiac outcomes, in-hospital deaths for any cause, post-procedure AMI, and emergency CABG were considered.
For the statistical analysis, the Statistical Package for Social Science (SPSS) version 19 (SPSS inc, Chicago, USA) was used.The Chi-squared test was used to compare categorical variables.Analysis of variance was used for continuous variables and Bonferroni correction for multiple comparisons.To test the association of the variables of interest with in-hospital mortality, simple and multiple logistic regression models were used.In this case, the va riables were adjusted for sex using the forward selection method, which determined the independent variables that would best explain the occurrence of death.Variables with a high percent of missing values, such as Killip class, left ventricular dysfunction and presence of collateral circulation, were not included in the multiple logistic regression analysis; thus, the sample used in this model contained 23,781 patients.In all analyses, a significance level of 5% (p < 0.05) was adopted.

Results
Between June 2006 and March 2016, 24,895 patients with coronary atherosclerotic disease with involvement of at least one smallcaliber artery were included in the study, totaling 25,892 treated vessels (mean of 1.04 per patient), with the use of 28,053 stents (mean of 1.13 per patient).
Patient characteristics are shown in Table 1; 59.7% were males, with a mean age of 63.3 years, and 26.1% had diabetes.The preponderant clinical presentation was stable angina (47.5%).Compared to the other periods, among the patients treated in 2012-2016, there were higher prevalences of male patients, previous AMI and previous PCI as well as lower rates of diabetes, smoking, hypertension, dyslipidemia and previous MRS.There was a progressive increase in the number of asymptomatic patients or patients with acute coronary syndrome (ACS) as a clinical presentation.
The anterior descending artery was the most frequently treated vessel (46.6%), with 59.7% of the patients presenting with single-vessel disease.There was a predominance of type B 2 /C lesions (65.0%), with 22.4% long lesions, 23.8% bifurcations and 13.6% chronic occlusions (Table 2).There was an increase in the prevalence of complex lesions in the period.Among the stents used, 25.5% were drug-eluting, with mean diameter and length of 2.47 mm and 18.1 mm, respectively.Angiographic success was obtained in 98.2% of the cases (Table 3).There was a greater use of drug-eluting stents, increase in their mean length and decrease in the diameter of the devices over the years.
Univariate (Table 5) and multivariate analysis (Table 6) were performed, and the following variables showed an independent association with death: procedures performed in the 2006-2008 triennium, age, smoking, diabetes, unstable clinical condition, multivessel disease, emergency interventions and use of glycoprotein IIb/IIIa inhibitors.

Discussion
][13] From the angiographic point of view, there was a decrease in multivessel disease and an increase in the anatomical complexity of the lesions.There was also greater use of drug-eluting stents, longer total stent length and greater use of manual aspiration thrombectomy, in addition to a high procedure success rate.
The rate of serious adverse cardiac events was lower than reported in the literature, particularly for mortality (0.6%).In a US cohort study that included almost 200,000 procedures, in-hospital mortality was 1.27%. 14In 2010, data from the Hospital Information System of the Unified Health System (Sistema de Informações Hospitalares do Sistema Único de Saúde -SIHSUS) on 166,514 PCIs performed in 180 Brazilian hospitals were published, in which the in-hospital mortality was 2.33%. 15A subanalysis of the DESIRE (Drug-Eluting Stents In the Real World) registry evaluated 1,380 patients undergoing PCI in small-caliber arteries who had an epidemiological profile and     angiographic characteristics similar to those of this study, revealing an incidence of death and AMI of 4.5% and 4.2%, respectively. 7Finally, a recent meta-analysis of randomized clinical trials, which compared the different devices used for PCI in small-caliber arteries, reported a total mortality of 1.3%. 16he lower occurrence of in-hospital outcomes in relation to the other studies can be explained by the lower cardiovascular risk in the study population.The control of risk factors is responsible for an approximately 50% reduction in mortality from cardiovascular diseases. 17The increase in utilization of drug-eluting stents observed in this study, although it is known to reduce the incidence of restenosis and revascularization of the target vessel, does not justify the reduction in mortality observed in our series. 18,19ecause this is a cross-sectional study, it is not possible to establish a causal relationship between the studied variables and the outcomes.By restricting the analysis of the outcomes to the in-hospital period, evaluation of restenosis and new revascularization of the target vessel, often associated with PCI in small-caliber arteries, are impossible.Finally, the lack of validation of the data provided to the CENIC and the voluntary nature of the data collection, which could induce a low inclusion of unsuccessful procedures or procedures with adverse events, restrict the reproducibility of these numbers and constitute an important limitation.

Conclusions
In patients undergoing percutaneous coronary intervention in small-caliber arteries registered in the CENIC, significant reductions in the rates of death, acute myocardial infarction and emergency coronary artery bypass graft surgery in the last 10 years were observed.This result was possibly due to the decrease in the prevalence of cardiovascular risk factors in the study population.There was an increase in the complexity of treated lesions and a greater use of drug-eluting stents in this period.Additional prospective studies are needed to confirm these findings.

Table 6
Multivariate analysis for the outcome mortality