INTRODUCTION: The prevention of contrast-induced nephropathy (CIN) is difficult in emergency
situations, making it essential to study CIN in patients submitted to urgent
OBJECTIVE: To determine the incidence and associated factors to CIN in patients with myocardial infarction (MI) submitted to primary angioplasty in the first 12 hours after onset of symptoms.
METHODS: We studied 201 consecutive cases of MI with ST-segment elevation with less than 12 hours of evolution. All patients were submitted to the same angioplasty protocol. CIN was defined as an absolute increase of creatinine of at least 0.5 mg/dL and/or a relative increase of creatinine of 25% in relation to baseline in a period between 48 and 72 hours after contrast administration. The variables that differed between patients with and without CIN in univariate analysis were analyzed by logistic regression.
RESULTS: The sample was formed by 135 (67.2%) men and 66 (32.8%) women, with mean age of 66.6 ± 11.7 years. The incidence of CIN was 23.8%. In univariate analysis the patients with CIN were older and had higher frequency of left ventricular ejection fraction = 40% and Killip classification = 2. In multivariate analysis, we did not find independent predictors of CIN.
CONCLUSION: CIN occurred in ¼ of the patients with MI submitted to angioplasty without predictor variables. This finding highlights the need for CIN preventive measures after contrast use in emergency angioplasty.
Keywords: acute kidney injury; angioplasty, balloon, coronary; contrast media; myocardial infarction.
INTRODUÇÃO: A prevenção da nefropatia induzida por contraste (NIC) é difícil nas situações de
emergência, tornando essenciais estudos sobre NIC em pacientes submetidos à
angioplastia de urgência.
OBJETIVO: Determinar a incidência e fatores associados à NIC em pacientes com infarto agudo do miocárdio (IAM) submetidos à angioplastia nas primeiras 12 horas após início dos sintomas.
MÉTODOS: Foram estudados 201 casos consecutivos de IAM com supradesnivelamento do segmento ST com menos de 12 horas de evolução. Todos os pacientes foram submetidos ao mesmo protocolo de angioplastia. A NIC foi definida como elevação absoluta da creatinina de pelo menos 0,5 mg/dL e/ou aumento relativo da creatinina de 25% em relação ao valor basal no período entre 48 e 72 horas após a administração do contraste. As variáveis que diferiram entre os pacientes com e sem NIC na análise univariada foram analisadas por regressão logística.
RESULTADOS: A amostra foi formada por 135 (67,2%) homens e 66 (32,8%) mulheres com idade média de 66,6 ± 11,7 anos. A incidência de NIC foi de 23,8%. Na análise univariada os pacientes com NIC eram mais idosos e com maior frequência de fração de ejeção do ventrículo esquerdo = 40% e da classificação Killip = 2. Na análise multivariada não foram encontrados preditores independentes de NIC.
CONCLUSÃO: A NIC acomete ¼ dos pacientes com IAM submetidos à angioplastia sem variáveis preditoras. Esse resultado ressalta a necessidade de medidas preventivas para NIC após uso de contraste em angioplastia de urgência.
Palavras-chave: angioplastia coronária com balão; infarto do miocárdio; lesão renal aguda; meios de contraste.
|Citation: Santos PR, Carneiro Neto JD, Arcanjo FPN, Carneiro JKR, Carneiro RCCP, Amaral CL. Contrast-induced nephropathy after primary angioplasty for acute myocardial infarction. Braz. J. Nephrol. (J. Bras. Nefrol.) 37(4):439. doi:10.5935/0101-2800.20150070|
|Received: Maio 13 2015; Accepted: Agosto 03 2015|
Acute myocardial infarction (AMI) is a common disease associated with high morbidity/mortality and high treatment costs.1 In recent decades there has been a significant reduction in mortality in patients with AMI with ST-segment elevation (STEMI) due to several factors, especially early diagnosis and treatment, advances in relation to the management of complications, such as recurrent ischemia and heart failure, and increased availability of pharmacological and mechanical reperfusion therapies.2,3 Despite this, AMI still represents a major cause of death in developed countries.1
Primary percutaneous coronary intervention (PPCI) is a safe and effective strategy in the treatment of STEMI, able to significantly reduce mortality compared to treatment by thrombolysis.3,4 However, the contrast media used during PPCI may cause allergic reactions and acute deterioration of kidney function.5
The incidence of contrast-induced nephropathy (CIN) varies widely depending on sample-related-factors, such as age, diabetes, renal function prior to contrast infusion, type and volume of contrast used. For this reason, we need evidence generated in multiple care settings for better understanding CIN. This study meets this need.
CIN after primary PCI is a complication that negatively affects both morbidity and mortality during hospitalization in the long run.6 The main prevention measure against CIN is hydration with saline prior to contrast use and preferably for a period of time, and such action is impossible to be performed in emergency situations such as AMI. The difficult prophylaxis, combined with the clinical severity of AMI, makes CIN quite prevalent and a subject of great interest in patients undergoing primary angioplasty for acute myocardial infarction. The study aimed to establish the incidence and possible factors associated with CIN in patients with acute myocardial infarction undergoing reperfusion therapy with primary angioplasty within 12 hours after symptoms onset.
We studied consecutive STEMI patients with less than 12 hours of evolution and treated with PPCI at the Heart Hospital of the Santa Casa de Misericordia de Sobral from March 2013 to June 2014. The hospital is a reference center in heart care for the entire Northwest region of the state of Ceará, made up of 47 municipalities and with a population estimated at 1,300,000 inhabitants. Exclusion criteria were age below 18 years, exposure to contrast media in the 30 days prior to enrollment in the study, death before the 48 hours following the contrast administration, chronic kidney disease (data accessed through records and medical reports of the patients or examination showing glomerular filtration rate < 60 mL/min/1.73m2 for more than three months), AMI in saphenous vein bypass grafts, "culprit" vessel for the AMI with a diameter < 2.5 mm, coronary lesions with length > 64 mm, need for emergency coronary artery bypass surgery and previous use of thrombolytic agent. The patients in the sample were prospectively evaluated and are characterized by cases of STEMI patients submitted to PPCI with persistent chest pain for over 30 minutes and associated with ST-segment elevation of at least 0.1 mV in two or more contiguous electrocardiographic leads, with hospital admission within 12 hours after symptoms onset; and patients with chest pain for more than 30 minutes and/or new left branch block. All patients participating in the study signed an informed consent form and the study was approved by the Ethics Committee of the Federal University of Ceará (protocol under 143,737).
PPCI was performed according to the following protocol in all patients: cannulation of the femoral or the radial artery; use of fractionated intravenous heparin (100 IU/kg) after cannulation; introduction of 6F guide-catheter into the coronary artery ostium; and injection of low-osmolar ioxaglate 320 mgl/ml (Hexabrix®) contrast. The coronary flow of the infarct-related artery before and after PPCI was visually graded according to the TIMI flow classification.7 This classification considers four types of degrees: grade 0 - no antegrade flow beyond the occlusion point; grade 1 - the contrast medium reaches place upstream of the obstruction, but without opacification of the distal coronary bed; Grade 2 - passage of the contrast through the obstruction with distal bed opacification, but slowly; Grade 3 - Complete coronary perfusion with antegrade flow in the distal bed, occurring readily as in the proximal coronary bed.
All patients were treated with coronary stents and with the drugs commonly used in PPCI, such as acetylsalicylic acid, clopidogrel or ticagrelor. The use or nonuse of glycoprotein IIb/IIIa inhibitors and manual vacuum were at the discretion of the interventional cardiologist who performed the procedure.
CIN was the main study endpoint, defined as an absolute increase in serum creatinine of at least 0.5 mg/dL or a relative serum creatinine increase of 25% compared to baseline (= serum creatinine upon admission) or a combination of both, from 48 to 72 hours after contrast administration.8
The following data was collected: age, gender, body mass index (kg/m2), body surface area (m2), comorbidities (hypertension, diabetes and dyslipidemia), smoking, medication use (specifically statins, converting enzyme inhibitors, diuretics, beta-blockers, oral hypoglycemic agents and insulin), family history of coronary artery disease, previous occurrence of cerebral vascular accident (stroke), myocardial infarction, coronary catheterization and coronary artery bypass surgery, arterial mean pressure, systolic and diastolic blood pressure before contrast use, contrast volume used, daily hemoglobin and serum creatinine values upon admission, 48 and 72 hours after infusion of contrast. Left ventricular ejection fraction was calculated using left ventriculography in diastole and systole, in the right anterior oblique projection. Data collected regarding PPCI was mean time of ischemia (= interval in minutes between the onset of symptoms and the first balloon inflation), time pain-door (= interval in minutes between the onset of symptoms and the first hospital care) and door-to-balloon time (= time in minutes between the first hospital care and the first balloon inflation). The Killip classification was used for staging the degree of heart failure.9
The success of primary PCI was defined as angiographic success in the absence of major complications, such as death, myocardial infarction and/or a need for further urgent revascularization. Bleeding complications were defined according to the criteria from the Thrombolysis in Myocardial Infarction10 as: minimal (any clinical sign of hemorrhage associated with falling hemoglobin < 3 g/dL), lower (clinical signs of bleeding associated with a hemoglobin drop of 3 g/dL to 5 g/dL) and higher (intracranial bleeding, clinically significant sign of bleeding associated with the drop in hemoglobin > 5 g/dL or fatal bleeding). The following adverse events were also considered: cardiac death, reinfarction and stroke. Reinfarction was diagnosed by the appearance of a new Q wave in two or more contiguous leads or elevated creatine kinase MB fraction greater than three times the upper normal limit. Stroke was defined as loss of neurological function lasting longer than 24 hours or by the presence of a new area of cerebral infarction by imaging techniques, regardless of symptoms duration.
The values of continuous variables were presented as mean ± standard deviation. Categorical variables were presented as absolute values and percentage. Ratio differences were evaluated by Fisher's exact and chi-square tests when indicated. The normal distribution of continuous variables was calculated by the Shapiro-Wilk test. The Student t-test (for normal distribution) and Mann-Whitney test (for not normal distribution) were used to compare continuous variables. The variables that differed between patients with and without CIN were analyzed by logistic regression using the stepwise backward method with the Wald statistics as to a possible association with CIN. Odds ratio (OR) and their respective confidence intervals (95% CI) were presented to quantify the effects.
The sample consisted of 201 patients. Four patients had died before the 48 hours after hospital admission and therefore were taken off the sample. No patient underwent dialysis at least within 72 hours after hospital admission. There were 135 (67.2%) men and 66 (32.8%) women with a mean age of 66.6 ± 11.7 years. The main arteries related to AMI were the anterior descending coronary artery (45.8%) and the right coronary (38.8%), followed by the circumflex artery (13.9%) and left main coronary artery (1.5%). The mean contrast medium volume used in primary PCI was 137.3 ± 7.5 ml. The incidence of CIN was 23.8%.
There was no difference between the values of baseline serum creatinine on admission among patients with and without CIN, respectively, 0.9 ± 0.1 mg/dL versus 1.0 ± 0.1 mg/dL (p = 0.547). As expected, serum creatinine levels after 48 and 72 hours were higher among patients who developed CIN, respectively 1.3 ± 0.9 mg/dl versus 1.0 ± 0.1 mg/dl (p < 0.001) and 1.4 ± 1.1 mg/dl versus 1.0 ± 0.1 (p < 0.001).
When comparing patients with and without CIN, patients with CIN were older (69.6 ± 11.4 versus 65.7 ± 11.6 years; p = 0.040), had a higher frequency of left ventricular ejection fraction = 40% (16.7% versus 4.6%; p = 0.010) and a higher incidence of Killip classification = 2 (18.7% versus 7.1%; p = 0.019). The other comparisons of demographic, clinical and angiographic characteristics regarding the procedure between patients with and without CIN did not differ and are presented on Tables 1 and 2. The frequency of death, PPCI clinical success and adverse events did not differ between patients with and without CIN (Table 3).
|Variables||Without CIN||With CIN||p|
|Age (years)||65.7 ± 11.6||69.6 ± 11.4||0.040|
|Men||74 (54,8)||61 (45.2)||0.135|
|Body Mass Index (kg/m2)||26.8 ± 3.4||26.4 ± 2.8||0.498|
|Body Surface (m2)||1.7 ± 0.1||1.7 ± 0.1||0.496|
|Risk factors for coronary disease|
|Arterial Hypertension||54 (35.2)||20 (41.6)||0.424|
|Dyslipidemia||59 (38.5)||16 (33.3)||0.513|
|Diabetes||22 (14.3)||10 (20.8)||0.286|
|Smoking||79 (51.6)||18 (375)||0.087|
|Family history of coronary disease||21 (13.7)||4 (8.3)||0.453|
|History of stroke||6 (3.9)||1 (2.0)||0.470|
|Prior myocardial infarction||7 (4.5)||1 (2.0)||0.391|
|Prior coronary intervention||5 (3.2)||1 (2.0)||1.000|
|Prior surgical revascularization||11 (71)||2 (4.1)||0.360|
|Baseline creatinine (mg/dL)||1.0 ± 0.1||0.9 ± 0.1||0.547|
|Creatinine after 48 hours (mg/dL)||1.0 ± 0.1||1.3 ± 0.9||< 0.001|
|Creatinine after 72 hours (mg/dL)||1.0 ± 0.1||1.4 ± 1.1||< 0.001|
|Mean time of ischemia (min)*||378.4 ± 192.2||348.1 ± 149.7||0.449|
|Pain-door time (min)**||311.2 ± 154.6||2978 ± 150.5||0.597|
|Door-balloon time (min)***||76.2 ± 142.3||50.3 ± 18.8||0.136|
|Door-balloon time > 90 min||10 (6.5)||3 (6.3)||0.622|
|Left ventricle ejection < 40%||7 (4.6)||8 (16.7)||0.010|
|Killip = 2||11 (71)||9 (18.7)||0.019|
|Measurement in use|
|Statin||18 (11.7)||7 (14.5)||0.605|
|Angiotensin Converting Enzyme inhibitor||51 (33.3)||17 (35.4)||0.790|
|Diuretic||4 (2.6)||2 (4.2)||0.440|
|Beta-blockers||2 (1.3)||1 (2.1)||0.561|
|Oral hypoglycemic agent||17 (11.1)||8 (16.7)||0.308|
|Insulin||6 (3.9)||2 (4.2)||0.608|
|Variables||Without CIN||With CIN||p|
|Artery related to the infarction|
|Left coronary trunk||3 (2.0)||0 (0)||0.438|
|Anterior descending||69 (45.1)||23 (479)||0.732|
|Circumflex||20 (13.1)||8 (16.7%)||0.530|
|Right coronary||61 (39.9)||17 (35.4%)||0.580|
|Contrast volume (ml)||1372 ± 78||137.1 ± 7.3||0.956|
|MAP upon angioplasty onset (mmHg)||94.6 ± 176||91.2 ± 14.3||0.227|
|SBP upon angioplasty onset (mmHg)||130.8 ± 25.3||125.0 ± 21.9||0.151|
|DBP upon angioplasty onset (mmHg)||76.5 ± 15.7||74.3 ± 11.6||0.373|
|Ilb/IIIa glycoprotein inhibitor||8 (5.2)||3 (6.3)||0.512|
Results in mean ± standard deviation and percentages within parenthesis. MAP: Mean Arterial Pressure; SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure.
|Variables||Without CIN||With CIN||p|
|Angioplasty clinical success||136 (88.8)||44 (91.6)||0.583|
|Cerebral vascular accident (stroke)||3 (2.0)||0||0.438|
|Larger bleeding||6 (3.9)||1 (2.0)||0.470|
|Death||13 (8.5)||4 (8.3)||0.614|
Percentage within parenthesis.
In the multivariate analysis, considering the variables that differed between patients with and without CIN, there were no independent predictors of risk for the development of CIN (Table 4).
|Variables||Univariate analysis||Multivariate analysis|
|OR||IC 95%||p||OR||IC 95%||p|
|LVEF = 40%||4.17||1.42-12.19||0.009||3.09||0.63-15.07||0.162|
|Killip = 2||2.29||1.08-4.89||0.031||1.22||0.39-3.77||0.728|
LVEF: left-ventricle ejection fraction.
Our study showed the incidence of CIN in ¼ of the patients who underwent coronary angiography due to AMI. The incidence of CIN following coronary angiography varies greatly depending on the demographic and clinical variables of the sample, as well as the characteristics of the angiography. After cardiac catheterization, the incidence of CIN may be as low as 6% in patients undergoing elective catheterization (diagnosis);11 approaching 16% in samples encompassing both cases of elective and urgent catheterization;12 and it reaches 25% in samples such as ours, involving urgent catheterization.13
In our study it was not possible to identify the variables that traditionally increase the risk of CIN onset. The variables that differed in the comparison of patients with and without CIN were not independent predictors in the multivariate analysis. They were: older age, left ventricle ejection fraction = 40% and Killip = 2. In traditional risk scores for CIN, such as Mehran14 and Bartholomew,15 these three variables generate points in their respective forecast ranges of risk categorized as "age > 75 years" and "degree of heart failure" (in our study the degree of heart failure was estimated by the left ventricle ejection fraction and the Killip classification).
Despite the high incidence of CIN, as we have in this type of sample (urgent catheterization due to AMI), we could find "protective" characteristics concerning the occurrence of CIN, such as average age below 75 years; Low infused contrast volume (in our study the average infused volume was 137.3 ml, well below the cut off points of risk listed in the literature: for some > 200 ML16 and others > 300 ML12); low average serum creatinine on admission with only four patients with serum creatinine greater than 2 mg/dL, which prevented comparisons of statistical value among patients with creatinine equal to or lower versus higher than 2 mg/dL (creatinine limit is usually used as a risk criteria for CIN); few patients with previous PPCI and mean ischemia time of less than 6 hours. Prior PPCI and ischemia time greater than six hours were risk factors in previously published studies.12,13
But even with the "protective" characteristics seen in the sample, CIN incidence was quite high, indicating the need for preventive measures. The first point is to consider all patients with acute myocardial infarction undergoing primary PCI as having high risk for developing CIN. The most effective preventive measure, which is hydration prior to use of contrast, is difficult to perform due to the emergency nature of AMI. Thus, drugs that could be used immediately before contrast infusion would be the ideal preventative measure. With regards to N-acetylcysteine, despite being studied for a long time, data is still conflicting as to its power to prevent CIN after coronary angiography studies.17 Pentoxifylline was not protective for the occurrence of CIN in low-risk samples (elective coronary angiography),18,19 we are still missing data on patients undergoing emergency coronary angiography. In a recent meta-analysis, intravenous fenoldopam was not superior to saline or N-acetylcysteine.20 Rosuvastatin and atorvastatin are promising drugs that have proven effective in preventing CIN in a meta-analysis based on randomized clinical trials.21
In our study, CIN was not associated with mortality or adverse advents in the short term (72 hours). It is known, however, that CIN increases by 14.4% the death rate within 30 days and 17.4% after three years.17
In our opinion, the importance of this study is to fill the information gap about CIN after urgent AMI coronary angiography in cardiology services in Brazil. Still waiting for multicenter studies, it is essential to have anecdotal reports from various services that can demonstrate the incidence and factors associated with CIN, as a first step towards the organization of a body of evidence that enables the proposal of strategies to prevent the alarming incidence of ¼ CIN after PPCI in AMI cases.
First, the lack of factors traditionally associated and predictors of CIN in our study may be due to the small sample size. Second, the short follow-up precluded the finding of adverse outcomes, either death or complications in the medium and long terms. Third, there was an exclusion of patients recently submitted to any kind of contrast media. Previous use of contrast is a recognized risk for CIN. Thus, the inclusion of these patients could have been interesting, considering that currently this group of patients undergoing repeated contrast studies corresponds to a considerable portion. Fourth, there are creatinine limitations in the context of acute renal injury. Currently, studies using biomarkers point to the role of NGAL in both the risk of detecting (by the dosage prior to the use of contrast) as in the early diagnosis (by measuring it one day after the use of contrast) CIN. Despite the limitations, our study confirms the high incidence of CIN in patients with acute myocardial infarction undergoing primary PCI and highlights the need for randomized clinical trials concerning prophylactic measures in urgent angiograms.
CIN affects ¼ of patients with acute myocardial infarction undergoing primary PCI, without a variable that can predict its occurrence and with no association with death and/or adverse advents in the short term. The high incidence points to the need for studies on preventive measures for CIN after contrast use in emergency angiography.