Abstract
Background
Although remote ischemic post-conditioning (RIPC) has been shown to prevent contrast-induced acute kidney injury (CIAKI) in patients with acute coronary syndrome, its efficacy in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. We examined the relationship among balloon inflations and deflations (BID) times, SYNTAX score of infarction-related artery (SI), periprocedural complications, and CIAKI in STEMI patients undergoing primary percutaneous coronary intervention (pPCI).
Methods
Patients with STEMI undergoing pPCI with Mehran risk score (MRS) ≥ 5 were enrolled between February 2007 and September 2012. The study end point was the development of CIAKI.
Results
Of 206 patients, the median age was 65 years [interquartile range (IQR): 55-77] with 72.8% male and Mehran risk score (MRS) 8 (IQR: 6-12). Receiver operating characteristic curve showed that BID times > 9 times or SI > 10 was the best cut-off associated with CIAKI. In univariate analysis, significant association with CIAKI existed in BID > 9 times [odds ratio (OR): 3.106, 95% confidence interval (CI): 1.284-7.513, p = 0.012] and SI > 10 (OR: 3.909, 95% CI: 1.570-9.735, p = 0.003). Other variables associated with CIAKI included creatinine, hemoglobin, angiotensin converting enzyme inhibitor or angiotensin receptor blocker use at discharge. In multivariate analysis, SI > 10 remained an independent predictor of CIAKI in different adjustment model, even on top of MRS (adjusted OR: 3.498, 95% CI: 1.086-11.268, p = 0.036).
Conclusions
Vascular complexity of infarct-related artery rather than higher BID times (> 9) was the major determinant of the development of CIAKI after pPCI in STEMI patients.
Keywords: Acute kidney injury, Acute myocardial infarction, Primary percutaneous coronary intervention
INTRODUCTION
The development of contrast-induced acute kidney injury (CIAKI) is associated with both short- and long-term adverse events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).1-6 A novel technique, known as remote ischemic post-conditioning (RIPC), has been used successfully to avoid CIAKI in patients with ACS. In cases involving acute myocardial myocardial infarction, results from both animal models and human studies have shown an association between ischemic post-conditioning (IPC) and myocardial infarct size.7,8 However, specific evidence that correlates RIPC and kidney function is limited in these patients. Some studies have suggested that RIPC by means of coronary balloon inflation had a protective effect on kidney function during angioplasty.9,10 Nevertheless, it is unclear if RIPC has the same effect on preservation of kidney function in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. Therefore, the goal of this study was to determine if the number of coronary balloon inflations and deflations (BID), which mimicked RIPC, was associated with CIAKI. In addition, we sought to ascertain potential predictors of CIAKI, such as thrombolysis in myocardial infarction (TIMI) flow before and after primary PCI, complexity of infarct-related artery (IRA), and development of periprocedural complications.11
MATERIAL AND METHODS
Study design
Between February 2007 and September 2012, we conducted a retrospective cohort study on consecutive patients admitted to a single high-volume medical center in Northern Taiwan with the diagnosis of STEMI.12,13 All patients with a diagnosis of STEMI undergoing primary PCI and at intermediate risk of CIAKI [defined as the Mehran risk score (MRS) ≥ 5] were included for analysis. STEMI was diagnosed using the following criteria: 1) new ST elevation at the J point in at least two contiguous leads of ≥ 2 mm (0.2 mV) in men, or ≥ 1.5 mm (0.15 mV) in women in leads V2-V3 and/or of ≥ 1 mm (0.1 mV) in other contiguous chest leads or the limb leads; and 2) new or presumably new LBBB.14 We excluded those patients who were 1) on maintenance hemodialysis, and/or 2) had a paucity of door-to-balloon time, such as (a) STEMI transferred from another hospital or out-patient department, (b) STEMI which occurred within the hospital, (c) cardiac arrest before initiation of primary PCI, (d) difficult consent process, or (e) missing data. In those patients deemed eligible, the following data were collected by medical records: baseline demographics, full procedural details, and results of coronary angiography. The main therapeutic strategies underlying primary PCI at our hospital were thrombus aspiration if the culprit vessel was totally occluded, and use of glycoprotein IIb/IIIa inhibitor if no bleeding tendency existed. Iopamidol (370 mg of iodine per ml) was used during coronary angiography. All patients received standard care that adhered to current guidelines.12,14-16 The study was approved by the Institutional Review Board of Far Eastern Memorial Hospital in Taiwan.
Definitions
CIAKI was defined as: 1) an absolute elevation of serum creatinine > 0.5 mg/dl in patients with baseline serum creatinine ≤ 2.0 mg/dl, or 2) a relative increase of ≥ 25% from the baseline value in patients with baseline creatinine > 2.0 mg/dl within 96 hours after primary PCI was performed.
The MRS is acknowledged to be a simple predictor of risk for CIAKI in patients undergoing PCI.15 MRS is the summation of the following items: hypotension (5 points), intra-aortic balloon pump use (5 points), congestive heart failure (5 points, defined as New York Heart Association functional classification III/IV and/or history of pulmonary edema), age > 75 years (4 points), diabetes (3 points), anemia (3 points, defined as hematocrit < 39% in men and < 36% in women), and serum creatinine > 1.5 mg/dl (4 points).
The lesion complexity of IRA was represented as SYNTAX score of IRA (SI) in this study,11,17 After antegrade coronary flow was restored at IRA, and SI was calculated by using SYNTAX score calculator version 2.11 (http://www.syntaxscore.com/calc/start.htm). Dissection was defined according to the National Heart, Lung and Blood Institute classification system. Periprocedural complications were defined as a composite of dissection and acute no-reflow.
Study endpoints
We examined the relationships among the number of BIDs performed, SYNTAX score, periprocedural complications, potential confounders and CIAKI in our patients. The primary endpoint was CIAKI. All-cause in-hospital mortality, 30-day and 1-year mortality, and myocardial infarct size were collected using medical records and telephone surveys.
Statistical analysis
Categorical or continuous variables were expressed as number and percentage, or median and interquartile range (IQR), respectively. The chi-square test was used for categorical variables, and the Mann-Whitney test was utilized for continuous variables. The receiver operating characteristic (ROC) curve was used to determine the relationships between the number of BIDs performed and CIAKI, and between SYNTAX score and CIAKI. The associations between all variables and CIAKI were examined by univariate logistic regression analyses. If significant association existed between those variables and CIAKI in univariate analyses, multivariate analyses were used for further investigation. If there were a trend toward significant association (p < 0.09) between CIAKI and variables, those variables would be adjusted as confounders in multivariate analysis. All p values were two-tailed, and a p value < 0.05 was considered statistically significant. Analysis was performed using SPSS software, version 18.0.
RESULTS
A total of 206 patients were enrolled and analyzed in this investigation. The study flow sheet was illustrated in Figure 1. These patients had a median age of 65 years (IQR: 55-77), body mass index 24.6 kg/m2 (IQR: 22.2-26.9), creatinine 1.11 mg/dl (IQR: 0.85-1.47), hemoglobin 13.9 mg/dl (12.2-15.3), and 72.8% of the patients were male. Other baseline characteristics were listed in Table 1. Coronary angiography showed 73.2% of patients with multi-vessel disease. During diagnostic coronary angiography, 70.9% of these patients had TIMI 0 flow, and only 1.5% of them still had TIMI 0 flow after primary PCI was performed. All patients received successful PCI except 4 patients. One of those 4 patients with inferior-STEMI received alternative PCI to the circumflex artery because of failure of PCI to the right coronary artery. Another 3 patients underwent failed PCI, with a final TIMI 0 flow. CIAKI did not develop in these patients with failure PCI. Bare-metal stents (BMS) were implanted in 80.6% of patients and drug-eluting stents (DES) were implanted in 8.7% of patients. One patient received simultaneous BMS and DES implantation. One patient received successful thrombus aspiration without any stent implantation. The rest of the 21 patients received percutaneous occlusive balloon angioplasty for in-stent restenosis, small-caliber vessels, or an ectasia vessel. Dissection of all types developed in 51% of patients during PCI. Of these patients, type D and type F dissection accounted for 11.4% and 11.7% of patients, respectively. No patient experienced type C dissection during PCI. Other procedural characteristics and peri-procedural complications were shown in Table 2.
Figure 1.
Study flow sheet. CIAKI, contrast-induced acute kidney injury; MRS, Mehran risk score; PCI, percutaneous coronary intervention; pPCI, primary percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
Table 1. Baseline characteristics and outcomes in the STEMI patients undergoing primary PCI and MRS ≥ 5.
| Variables | All (N = 206) | BID ≤ 9 times (N = 139) | BID > 9 times (N = 67) | p value |
| Age (years) | 55 (65-77) | 64 (55-78) | 66 (58-76) | 0.583 |
| Body mass index (kg/m2) | 24.6 (22.2-26.9) | 24.8 (22.5-27.1) | 23.9 (22.0-26.4) | 0.364 |
| Creatinine (mg/dl) | 1.11 (0.85-1.47) | 1.1 (0.9-1.5) | 1.1 (0.9-1.6) | 0.612 |
| Hemoglobin (g/dl) | 13.9 (12.2-15.3) | 14.2 (12.5-15.4) | 13.7 (11.6-15.2) | 0.233 |
| CAD risk factors | ||||
| Male | 150 (72.8) | 105 (75.5) | 45 (67.2) | 0.242 |
| Current/past smoker | 99 (48.1) | 66 (47.5) | 33 (49.3) | 0.97 |
| Hypertension | 145 (70.4) | 95 (68.8) | 50 (74.6) | 0.418 |
| Diabetes | 96 (46.6) | 63 (45.7) | 33 (49.3) | 0.657 |
| Hyperlipidemia | 55 (26.7) | 41 (29.7) | 14 (21.2) | 0.239 |
| Known CAD | 32 (15.5) | 20 (14.5) | 12 (17.9) | 0.543 |
| Previous MI | 10 (4.9) | 6 (4.5) | 4 (6.1) | 0.734 |
| Ischemic stroke | 23 (11.2) | 15 (10.8) | 8 (11.9) | 0.839 |
| Killip class | ||||
| I | 78 (37.9) | 55 (39.6) | 23 (34.3) | 0.54 |
| II | 63 (30.6) | 41 (29.5) | 22 (32.8) | 0.632 |
| III | 19 (9.3) | 7 (5.0) | 9 (13.4) | 0.049 |
| IV | 46 (22.3) | 34 (24.5) | 12 (17.9) | 0.372 |
| MRS | 8 (6-12) | 8 (6-11) | 8 (6-12) | 0.22 |
| Hypotension | 46 (22.3) | 34 (24.5) | 12 (17.9) | 0.372 |
| IABP use | 61 (29.6) | 39 (28.1) | 22 (32.8) | 0.517 |
| Congestive heart failure | 16 (7.8) | 7 (5.0) | 9 (13.4) | 0.049 |
| Age > 75 (years) | 64 (31.1) | 43 (30.9) | 21 (31.3) | 1 |
| Anemiaa | 65 (31.6) | 42 (30.2) | 23 (34.3) | 0.632 |
| Creatinine > 1.5 (mg/dl) | 47 (22.8) | 30 (21.6) | 17 (25.4) | 0.596 |
| Medication use at discharge | ||||
| Aspirin | 195 (94.7) | 130 (93.5) | 65 (97.0) | 1 |
| Beta-blocker | 122 (59.2) | 86 (61.9) | 36 (53.7) | 0.148 |
| ACEI or ARB | 131 (63.6) | 93 (66.9) | 38 (56.7) | 0.167 |
| Outcomes | ||||
| CIAKI | 23 (11.2) | 10 (7.2) | 13 (19.4) | 0.016 |
| In-hospital mortality | 5 (2.4) | 3 (2.2) | 2 (3.0) | 1 |
| 30-day mortality | 10 (4.9) | 5 (3.6) | 5 (7.5) | 0.299 |
| 1-year mortality | 20 (9.7) | 13 (9.4) | 7 (10.4) | 0.805 |
Values were median (interquartile range) or n (%).
* New York Heart Association functional classification III/IV and/or history of pulmonary edema. # Hematocrit < 39% in men and < 36% in women.
ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BID, balloon inflations and deflations; CAD, coronary artery disease; CIAKI, contrast-induced acute kidney injury; IABP, intra-aortic balloon pump; MI, myocardial infarction; MRS, Mehran risk score; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
Table 2. Procedural characteristics and peri-procedural complications in patients with STEMI undergoing primary PCI and MRS ≥ 5.
| Variables | All (N = 206) | BID ≤ 9 times (N = 139) | BID > 9 times (N = 67) | p value |
| Procedural characteristics | ||||
| Numbers of BID performed | 7 (5-11) | 6 (4-7) | 14 (12-18) | < 0.001 |
| Contrast volume (ml) | 180 (150-200) | 160 (150-200) | 200 (180-260) | < 0.001 |
| Fluoroscopy times (min)* | 12.6 (9.8-18.1) | 11 (8.8-14.5) | 19.2 (13.7-25.4) | < 0.001 |
| Door-to-balloon time (min) | 76 (62-112) | 74 (60-107) | 81 (64-113) | 0.193 |
| Trans-femoral approach | 184 (89.3) | 129 (92.8) | 55 (82.1) | 0.02 |
| Thrombus aspiration | 116 (56.3) | 86 (61.9) | 30 (44.8) | 0.025 |
| Glycoprotein IIb/IIIa inhibitor | 122 (59.2) | 83 (59.7) | 39 (58.2) | 0.88 |
| IABP use | 53 (25.7) | 34 (24.5) | 19 (28.4) | 0.549 |
| Multiple-vessel disease | 150 (73.2) | 93 (66.9) | 57 (85.1) | 0.007 |
| IRA | ||||
| LAD | 96 (46.6) | 67 (48.2) | 29 (43.3) | 0.507 |
| Non-LAD | 110 (53.4) | 72 (51.8) | 38 (56.7) | 0.553 |
| LM | 2 (1) | 1 (0.7) | 1 (1.5) | 0.546 |
| Stent implantation# | 182 (88.3) | 118 (84.9) | 64 (95.5) | 0.035 |
| Bare-metal stent | 166 (80.6) | 110 (79.1) | 56 (83.6) | 0.573 |
| Drug-eluting stent | 17 (8.3) | 8 (5.8) | 9 (13.4) | 0.101 |
| Numbers of stent implantations | ||||
| 1 | 117 (56.8) | 95 (68.3) | 22 (32.8) | < 0.001 |
| 2 | 49 (23.8) | 22 (15.8) | 27 (40.3) | < 0.001 |
| 3 | 14 (6.8) | 1 (0.7) | 13 (19.4) | < 0.001 |
| 4 | 3 (1.5) | 0 (0) | 3 (4.5) | 0.033 |
| Initial TIMI flow* | ||||
| 0 | 146 (70.9) | 106 (76.3) | 39 (58.2) | 0.009 |
| 1 | 15 (7.3) | 8 (5.8) | 7 (10.4) | 0.257 |
| 2-3 | 45 (21.9) | 24 (17.3) | 21 (31.3) | 0.03 |
| Final TIMI flow* | ||||
| 0 | 3 (1.5) | 3 (2.2) | 0 (0) | 0.552 |
| 1 | 2 (1) | 2 (1.4) | 0 (0) | 1 |
| 2-3 | 201 (97.6) | 133 (67.0) | 67 (0.2) | 0.18 |
| PCI to non-IRA | 6 (2.9) | 3 (2.2) | 3 (4.5) | 0.395 |
| Heavy calcification of IRA | 33 (16) | 23 (16.7) | 10 (14.9) | 0.841 |
| IRA lesion > 20 mm | 173 (84) | 115 (83.3) | 58 (86.6) | 0.683 |
| Bifurcation lesion of IRA | 135 (65.5) | 89 (64.0) | 46 (68.7) | 0.536 |
| Side branch > 1.5 mm | 87 (42.2) | 54 (38.8) | 33 (49.3) | 0.177 |
| Side branch < 1.5 mm | 48 (23.3) | 35 (25.2) | 13 (19.4) | 0.385 |
| Periprocedural complications | ||||
| Any dissection | 105 (51) | 69 (50.0) | 36 (53.7) | 0.657 |
| Type D dissection | 12 (5.8) | 7 (5.1) | 5 (7.5) | 0.533 |
| Type F dissection | 18 (8.7) | 12 (8.7) | 6 (9.0) | 1 |
Values were median (interquartile range) or n (%).
* Thirty-two data missing for fluoroscopy times and one datum missing for TIMI flow. # One patient received simultaneous implantation of bare-metal (2.75 mm * 18 mm) and drug-eluting stent (2.25 mm * 16 mm).
BID, balloon inflations an deflations; IABP, intra-aortic balloon pump; IRA, infarct-related artery; LAD, left anterior descending artery; LM, left main coronary artery; MRS, Mehran risk score; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
The median number of BIDs performed on these patients was 7 (IQR: 5-11). ROC curve showed that the number of BIDs performed correlated with CIAKI [area under curve (AUC): 0.651, 95% confidence interval (CI): 0.541-0.760, p = 0.019]. The best cut-off point for the association between the number of BID performed and CIAKI was a BID equal to 9 times. The median of SI was 9 (IQR: 6-12); the ROC curve demonstrated that SI also was associated with CIAKI (AUC: 0.666, 95% CI: 0.539-0.794, p = 0.009). The best cut-off point for the association between SI and CIAKI was a score of 10. There were 67 patients (32.5%) receiving BID > 9 times, and 75 patients (36.4%) with SI > 10, respectively.
At discharge, all patients received clopidogrel and statin. Of these patients, 94.7% received aspirin, 63.6% of these patients received angiotensin-converting enzyme inhibitor (ACEI) or angiotension II receptor blocker (ARB), and 59.2% of these patients received beta-blockade. The incidence of death in hospital, 30-day mortality, and 1-year mortality were 2.4%, 4.9%, and 9.7%, respectively. Myocardial infarct size, expressed as a peak value of creatine kinase (CK) and CK-MB, were 1,169 IU/L (IQR: 2,700-4,899) and 229 U/L (IQR: 121-411), respectively. CIAKI occurred in 23 of 206 patients (11%), consistent with MRS prediction and previous studies.5,6,18 No CIAKI developed in patients with failure of PCI. If we divided these patients by the number of BIDs performed, there were 139 patients with BID ≤ 9 times and 67 patients with BID > 9 times, respectively. Baseline and procedural characteristics were similar in these two groups, except that patients with BID > 9 times received more contrast (200 ml, IQR: 180-260 vs. 160 ml, IQR: 150-200, p < 0.001) and had less single-vessel disease (14.9% vs. 33.1%, p = 0.006) than those with BID ≤ 9 times (detailed in supplemental Table 1 and Table 2). CIAKI rates were significantly higher in the BID > 9 times group compared with the BID ≤ 9 times group (19.4% vs. 7.2%, p = 0.016).
Supplemental Table 1. Subgroup analysis of STEMI patients regarding baseline kidney function.
| Variables | Creatinine ≤ 1.5 mg/dl | Creatinine > 1.5 mg/dl | ||||
| BID ≤ 9 times (N = 110) | BID > 9 times (N = 50) | p | BID ≤ 9 times (N = 29) | BID > 9 times (N = 17) | p | |
| Age (years) | 63 (54-79) | 66 (59-76) | 0.592 | 67 (56-76) | 68 (55-82) | 0.838 |
| Body mass index (kg/m2) | 24.7 (22.4-27.3) | 23.7 (21.9-26.4) | 0.193 | 24.8 (22.3-26.6) | 25.0 (22.2-27.7) | 0.725 |
| Creatinine (mg/dl) | 1 (0.8-1.3) | 0.9 (0.8-1.2) | 0.373 | 1.8 (1.6-2.4) | 2.4 (1.8-2.76) | 0.023 |
| Hemoglobin (g/dl) | 14.5 (12.6-15.5) | 14 (11.9-15.5) | 0.596 | 12.9 (12.4-15.3) | 12.1 (10.5-14.3) | 0.148 |
| CAD risk factors | ||||||
| Male | 80 (72.7) | 33 (66) | 0.455 | 4 (13.8) | 5 (29.4) | 0.258 |
| Current/past smoker | 51 (46.4) | 28 (56) | 0.514 | 15 (51.7) | 5 (29.4) | 0.219 |
| Hypertension | 74 (67.3) | 37 (74) | 0.464 | 21 (72.4) | 13 (76.5) | 1.000 |
| Diabetes | 49 (44.5) | 24 (48) | 0.735 | 14 (48.3) | 9 (52.9) | 1.000 |
| Hyperlipidemia | 31 (28.2) | 11 (22) | 0.560 | 10 (34.5) | 3 (17.6) | 0.315 |
| Known CAD | 14 (12.7) | 9 (18) | 0.467 | 6 (20.7) | 3 (17.6) | 1.000 |
| Previous MI | 6 (5.5) | 3 (6) | 1.000 | 0 (0) | 1 (5.9) | 0.386 |
| Ischemic stroke | 10 (9.1) | 7 (14) | 0.390 | 5 (17.2) | 1 (5.9) | 0.390 |
| Killip class | ||||||
| I | 47 (42.7) | 21 (42) | 1.000 | 10 (34.5) | 3 (17.6) | 0.315 |
| II | 33 (30.0) | 14 (28) | 0.853 | 8 (27.6) | 8 (47.1) | 0.213 |
| III | 7 (6.4) | 6 (12) | 0.229 | 0 (0) | 3 (17.6) | 0.045 |
| IV | 23 (20.9) | 9 (18) | 0.832 | 11 (37.9) | 3 (17.6) | 0.195 |
| Mehran risk score | ||||||
| Hypotension | 23 (20.9) | 9 (18) | 0.832 | 11 (37.9) | 3 (17.6) | 0.195 |
| IABP support | 33 (30.0) | 17 (34) | 0.713 | 6 (20.7) | 5 (29.4) | 0.722 |
| Congestive heart failure | 7 (6.4) | 6 (12) | 0.229 | 0 (0) | 3 (17.6) | 0.045 |
| Age > 75 (years) | 35 (31.8) | 14 (28) | 0.713 | 8 (27.6) | 7 (41.2) | 0.516 |
| Anemia | 31 (28.2) | 15 (30) | 0.852 | 11 (37.9) | 8 (47.1) | 0.757 |
| Procedural characteristics | ||||||
| Numbers of BID performed | 5 (4-7) | 14 (12-18) | < 0.001 | 6 (5-8) | 15 (12-18) | < 0.001 |
| Contrast volume (ml) | 160 (150-200) | 215 (180-285) | < 0.001 | 150 (150-200) | 200 (163-260) | 0.010 |
| Fluoroscopy times (min) | 10.6 (9-13.7) | 20.2 (14.1-26.0) | < 0.001 | 12.2 (8.0-16.5) | 15.8 (12.0-22.9) | 0.026 |
| Door-to-balloon time (min) | 74 (61-106) | 81 (64-115) | 0.178 | 78 (55-150) | 83 (64-131) | 0.690 |
| Trans-femoral approach | 103 (93.6)0 | 41 (82) | 0.043 | 26 (89.7) | 14 (82.4) | 0.655 |
| Thrombus aspiration | 66 (60.0) | 25 (50) | 0.302 | 20 (69.0) | 5 (29.4) | 0.014 |
| Glycoprotein IIb/IIIa inhibitor | 52 (47.3) | 26 (52) | 0.169 | 17 (58.6) | 11 (64.7) | 0.761 |
| IABP support | 0 (0) | 0 (0) | - | 5 (17.2) | 4 (23.5) | 0.707 |
| Multiple-vessel disease | 70 (63.6) | 43 (86) | 0.005 | 23 (79.3) | 14 (82.4) | 1.000 |
| Infarct-related artery | ||||||
| LAD | 59 (53.6) | 22 (44) | 0.307 | 8 (27.6) | 7 (41.2) | 0.516 |
| LM | 0 (0) | 0 (0) | - | 0 (0) | 1 (5.9) | 0.370 |
| Stent implantation# | 95 (86.4) | 49 (98) | 23 (79.3) | 16 (94.1) | 0.234 | |
| Bare-metal stent | 89 (80.9) | 41 (82) | 1.000 | 21 (72.4) | 15 (88.2) | 0.282 |
| Drug-eluting stent | 6 (5.5) | 8 (16) | 0.058 | 2 (6.9) | 1 (5.9) | 1.000 |
| Number of stent implantations | ||||||
| 1 | 77 (70.0) | 16 (32) | < 0.001 | 18 (62.1) | 6 (35.3) | 0.126 |
| 2 | 17 (15.5) | 22 (44) | < 0.001 | 5 (17.2) | 5 (29.4) | 0.462 |
| 3 | 1 (0.9) | 9 (18) | < 0.001 | 0 (0) | 4 (23.5) | 0.015 |
| 4 | 0 (0) | 2 (4) | < 0.001 | 0 (0) | 1 (5.9) | 0.370 |
| Initial TIMI flow | ||||||
| 0 | 82 (74.5) | 31 (62) | 0.134 | 24 (82.8) | 8 (47.1) | 0.019 |
| 1 | 7 (6.4) | 3 (6) | 1.000 | 1 (3.4) | 4 (23.5) | 0.055 |
| 2~3 | 21 (19.1) | 16 (32) | 0.104 | 3 (10.3) | 5 (29.4) | 0.125 |
| Final TIMI flow | ||||||
| 0 | 2 (1.8) | 0 (0) | 1.000 | 1 (3.4) | 0 (0) | 1.000 |
| 1 | 1 (0.9) | 0 (0) | 1.000 | 1 (3.4) | 0 (0) | 1.000 |
| 2~3 | 107 (97.3) | 50 (100) | 0.553 | 27 (93.1) | 17 (100.0) | 0.294 |
| PCI to non-IRA | 2 (1.8) | 3 (6) | 0.177 | 1 (3.4) | 0 (0) | 1.000 |
| Heavy calcification of IRA | 21 (19.1) | 5 (10) | 0.172 | 2 (6.9) | 5 (29.4) | 0.086 |
| IRA lesion > 20 mm | 93 (84.5) | 43 (86) | 1.000 | 22 (75.9) | 15 (88.2) | 0.690 |
| Bifurcation lesion of IRA | 72 (65.5) | 34 (68) | 0.453 | 17 (58.6) | 11 (64.7) | 0.578 |
| Side branch > 1.5 mm | 48 (43.6) | 27 (54) | 6 (20.7) | 6 (35.3) | ||
| Side branch < 1.5 mm | 24 (21.8) | 7 (14) | 11 (37.9) | 5 (29.4) | ||
| Periprocedural complications | ||||||
| Any dissection | 52 (47.3) | 26 (52) | 0.612 | 17 (58.6) | 10 (58.8) | 1.000 |
| Type D dissection | 3 (2.7) | 3 (6) | 0.378 | 4 (13.8) | 2 (11.8) | 1.000 |
| Type F dissection | 8 (7.3) | 5 (10) | 0.546 | 4 (13.8) | 1 (5.9) | 0.635 |
| Outcome | ||||||
| CIAKI | 5 (4.5) | 7 (14) | 0.052 | 3 (10.3) | 6 (35.3) | 0.058 |
Supplemental Table 2. Subgroup analysis of STEMI patients regarding vascular complexity.
| Variables | Simple vascular lesion (SI ≤ 10) | Complex vascular lesion (SI > 10) | ||||
| BID ≤ 9 times (N = 98) | BID > 9 times (N = 34) | p | BID ≤ 9 times (N = 41) | BID > 9 times (N = 33) | p | |
| Age (years) | 64 (54-78) | 67 (59-77) | 0.465 | 66 (55-88) | 64 (57-76) | 0.948 |
| Body mass index (kg/m2) | 22.1 (24.8-27.1) | 23.7 (22.0-26.5) | 0.297 | 24.8 (22.5-27.6) | 24.7 (22.23-26.6) | 0.826 |
| Creatinine (mg/dl) | 1.1 (0.9-1.5)0 | 1.1 (0.9-1.8)0 | 0.791 | 1.1 (0.9-1.8)0 | 1.0 (0.8-1.3) | 0.469 |
| Hemoglobin (g/dl) | 14.5 (12.6-15.4) | 14 (12.0-14.8) | 0.364 | 14.0 (12.0-14.8) | 13.0 (10.7-16.0) | 0.364 |
| CAD risk factors | ||||||
| Male | 25 (25.5) | 10 (29.4) | 0.658 | 9 (22.0) | 12 (36.4) | 0.202 |
| Current/past smoker | 52 (53.1) | 13 (38.2) | 0.273 | 21 (51.2) | 13 (39.4) | 0.354 |
| Hypertension | 68 (69.4) | 27 (79.4) | 0.374 | 27 (65.9) | 33 (100.0) | 0.805 |
| Diabetes | 47 (48.0) | 15 (44.1) | 0.694 | 16 (39.0) | 18 (54.5) | 0.242 |
| Hyperlipidemia | 29 (29.6) | 6 (17.6) | 0.257 | 12 (29.3) | 8 (24.2) | 0.793 |
| Known CAD | 14 (14.3) | 5 (14.7) | 1.000 | 6 (14.6) | 7 (21.2) | 0.545 |
| Previous MI | 5 (5.1) | 0 (0) | 0.325 | 1 (2.4) | 4 (12.1) | 0.172 |
| Ischemic stroke | 13 (13.3) | 5 (14.7) | 0.709 | 2 (4.9) | 3 (9.1) | 0.651 |
| Killip class | ||||||
| I | 39 (39.8) | 13 (38.2) | 1.000 | 16 (39.0) | 10 (30.3) | 0.472 |
| II | 29 (29.6) | 14 (41.2) | 0.288 | 12 (29.3) | 8 (24.2) | 0.793 |
| III | 3 (3.1) | 2 (5.9) | 0.603 | 5 (12.2) | 7 (21.2) | 0.352 |
| IV | 26 (26.5) | 4 (11.8) | 0.097 | 8 (19.5) | 8 (24.2) | 0.777 |
| Mehran risk score | ||||||
| Hypotension | 26 (26.5) | 4 (11.8) | 0.097 | 8 (19.5) | 8 (24.2) | 0.777 |
| IABP support | 20 (20.4) | 12 (35.3) | 0.104 | 19 (46.3) | 10 (30.3) | 0.231 |
| Congestive heart failure | 3 (3.1) | 2 (5.9) | 0.603 | 4 (9.8) | 7 (21.2) | 0.201 |
| Age > 75 (years) | 29 (29.6) | 11 (32.4) | 0.829 | 14 (34.1) | 10 (30.3) | 0.805 |
| Anemia | 26 (26.5) | 8 (23.5) | 0.823 | 16 (39.0) | 15 (45.5) | 0.640 |
| Procedural characteristics | ||||||
| Numbers of BID performed | 6 (4-7) | 13 (12-17) | < 0.001 | 6 (14-8) | 16 (12-19) | < 0.001 |
| Contrast volume (ml) | 160 (150-200) | 200 (160-260) | < 0.001 | 150 (150-200) | 230 (180-268) | < 0.001 |
| Fluoroscopy times (min)* | 11.3 (8.9-14.7) | 18.3 (14.1-26.1) | < 0.001 | 10.5 (8.7-13.1) | 19.7 (12.9-21.4) | < 0.001 |
| Door-to-balloon time (min) | 74 (59-108) | 81 (64-126) | 0.341 | 75 (60-110) | 81 (63-112) | 0.341 |
| Trans-femoral approach | 89 (90.8) | 28 (82.4) | 0.212 | 40 (97.6) | 27 (81.8) | 0.040 |
| Thrombus aspiration | 64 (65.3) | 14 (41.2) | 0.016 | 22 (53.7) | 16 (48.5) | 0.815 |
| Glycoprotein IIb/IIIa inhibitor | 64 (65.3) | 24 (70.6) | 0.675 | 19 (46.3) | 15 (45.5) | 1.000 |
| IABP support | 17 (17.3) | 10 (29.4) | 0.145 | 17 (41.5) | 9 (27.3) | 0.230 |
| Multiple-vessel disease | 65 (66.3) | 32 (94.1) | 0.001 | 28 (68.3) | 25 (75.8) | 0.606 |
| Infarct-related artery | ||||||
| LAD | 33 (33.7) | 3 (8.8) | 0.006 | 34 (82.9) | 26 (78.8) | 0.768 |
| LM | 0 (0) | 0 (0) | 1.000 | 1 (2.4) | 1 (3.0) | 1.000 |
| Stent implantation# | 83 (84.7) | 33 (97.1) | 0.069 | 35 (85.4) | 32 (97.0) | 0.296 |
| Bare-metal stent | 77 (78.6) | 29 (85.3) | 0.463 | 33 (80.5) | 27 (81.8) | 1.000 |
| Drug-eluting stent | 6 (6.1) | 4 (11.8) | 0.280 | 2 (4.9) | 5 (15.2) | 0.267 |
| Number of stent implantations | ||||||
| 1 | 70 (71.4) | 10 (29.4) | < 0.001 | 25 (61.0) | 12 (36.4) | 0.061 |
| 2 | 13 (13.3) | 14 (41.2) | 0.001 | 9 (22.0) | 13 (39.4) | 0.128 |
| 3 | 0 (0) | 8 (23.5) | < 0.001 | 1 (2.4) | 5 (15.2) | 0.083 |
| 4 | 0 (0) | 1 (2.9) | 0.258 | 0 (0) | 2 (6.1) | 0.195 |
| Initial TIMI flow | ||||||
| 0 | 72 (73.5) | 16 (47.1) | 0.011 | 35 (85.4) | 23 (69.7) | 0.155 |
| 1 | 6 (6.1) | 5 (14.7) | 0.150 | 2 (4.9) | 2 (6.1) | 1.000 |
| 2~3 | 20 (20.4) | 13 (38.2) | 0.064 | 4 (9.8) | 8 (24.2) | 0.119 |
| Final TIMI flow | ||||||
| 0 | 3 (3.1) | 0 (0) | 0.569 | 0 (0) | 0 (0) | - |
| 1 | 1 (1.0) | 0 (0) | 1.000 | 1 (2.4) | 0 (0) | 1.000 |
| 2~3 | 94 (95.9) | 34 (100). | 0.327 | 40 (97.6) | 33 (100.0) | 1.000 |
| PCI to non-IRA | 2 (2.0) | 2 (5.9) | 0.276 | 1 (2.4) | 1 (3.0) | 1.000 |
| Heavy calcification of IRA | 13 (13.3) | 3 (8.8) | 0.761 | 10 (24.4) | 7 (21.2) | 0.788 |
| IRA lesion > 20 mm | 78 (79.6) | 30 (88.2) | 0.433 | 37 (90.2) | 28 (84.8) | 0.501 |
| Bifurcation lesion of IRA | 52 (53.1) | 17 (50.0) | 0.918 | 37 (90.2) | 29 (87.9) | 0.914 |
| Side branch > 1.5 mm | 23 (23.5) | 8 (23.5) | 31 (75.6) | 25 (75.8) | ||
| Side branch < 1.5 mm | 29 (29.6) | 9 (26.5) | 6 (14.6) | 4 (12.1) | ||
| Periprocedural complications | ||||||
| Any dissection | 43 (43.9) | 16 (47.1) | 0.843 | 26 (63.4) | 20 (60.6) | 0.815 |
| Type D dissection | 5 (5.1) | 2 (5.9) | 1.000 | 2 (4.9) | 3 (9.1) | 0.651 |
| Type F dissection | 8 (8.2) | 3 (8.8) | 1.000 | 4 (9.8) | 3 (9.1) | 1.000 |
| Outcome | ||||||
| CIAKI | 4 (4.1) | 4 (11.8) | 0.203 | 6 (14.6) | 9 (27.3) | 0.246 |
In univariate analysis, BID > 9 times was significantly associated with CIAKI [Odds Ratio (OR): 3.106, 95% CI: 1.284-7.513, p = 0.012], although the significance did not exist when the number of BIDs performed was expressed as a continuous variable (OR: 1.045, 95% CI: 0.989-1.105, p = 0.118). Other variables associated with CIAKI included creatinine (OR: 1.960, 95% CI: 1.180-3.257, p = 0.009), hemoglobin (OR: 0.844, 95% CI: 0.720-0.989, p = 0.036), MRS (OR: 1.218, 95% CI: 1.101-1.348, p < 0.001), SI (OR: 1.157, 95% CI: 1.039-1.288, p = 0.008) or SI > 10 (OR: 3.909, 95% CI: 1.570-9.735, p = 0.003), as well as ACEI or ARB use at discharge (OR: 7.958, 95% CI: 2.815-22.493, p < 0.001). The association between CIAKI and multi-vessel disease was borderline significant (OR: 4.395, 95% CI: 0.996-19.401, p = 0.051). There were trends toward significant associations among CIAKI and age (OR: 1.031, 95% CI: 0.997-1.066, p = 0.071), any types of dissection during PCI (OR: 2.388, 95% CI: 0.938-6.081, p = 0.068), periprocedural complications (OR: 2.311, 95% CI: 0.908-5.882, p = 0.079) or beta-blockade use at discharge (OR: 0.405, 95% CI: 0.159-1.305, p = 0.059). No association existed in patients with acute no-reflow (OR: 0.988, 95% CI: 0.212-4.602, p = 0.988). Table 3 demonstrated associations among CIAKI and variables.
Table 3. Association between variables and CIAKI in STEMI patients undergoing primary PCI by univariate regression analysis.
| Variables | Crude OR | 95% CI | p value |
| Age (years) | 1.031 | 0.997-1.066 | 0.071* |
| Body mass index | 0.938 | 0.828-1.104 | 1.062 |
| Creatinine (mg/dl) | 1.96 | 1.180-3.257 | 0.009# |
| Hemoglobin (g/dl) | 0.844 | 0.720-0.989 | 0.036# |
| Killip class | 1.216 | 0.848-1.745 | 0.288 |
| I | 0.544 | 0.205-1.445 | 0.222 |
| II | 1.536 | 0.627-3.716 | 0.348 |
| III | 0.509 | 0.064-4.044 | 0.523 |
| IV | 1.615 | 0.621-4.202 | 0.326 |
| Mehran risk score | 1.218 | 1.101-1.348 | < 0.001# |
| IABP use | 2.504 | 1.026-6.114 | 0.044# |
| Congestive heart failure | 0.509 | 0.064-4.404 | 0.523 |
| Age > 75 (years) | 2.248 | 0.934-5.411 | 0.071 |
| Anemia | 1.458 | 0.596-3.566 | 0.409 |
| Creatinine > 1.5 (mg/dl) | 3.743 | 1.528-9.116 | 0.004 |
| Procedural characteristics | |||
| Multi-vessel disease | 4.395 | 0.996-19.41 | 0.051* |
| Contrast volume use (ml) | 1.001 | 0.992-1.009 | 0.906 |
| Fluoroscopy times (mins)† | 1.027 | 0.980-1.076 | 0.268 |
| IRA-LAD | 1.566 | 0.653-3.755 | 0.314 |
| Initial TIMI flow | 0.862 | 0.570-1.303 | 0.481 |
| Final TIMI flow | 1.172 | 0.435-3.158 | 0.753 |
| SYNTAX score of IRA‡ | 1.157 | 1.039-1.288 | 0.008# |
| SYNTAX score > 10 of IRA‡ | 3.909 | 1.570-9.735 | 0.003# |
| PCI to non-IRA | 4.238 | 0.732-24.55 | 0.107 |
| Numbers of BID performed | 1.045 | 0.989-1.105 | 0.118 |
| BID > 9 times | 3.106 | 1.284-7.513 | 0.012# |
| Door-to-balloon time (mins) | 1.000 | 0.994-1.007 | 0.897 |
| Trans-femoral approach | 2.852 | 0.365-22.26 | 0.318 |
| Thrombus aspiration | 0.681 | 0.286-1.624 | 0.386 |
| Glycoprotein IIb/IIIa inhibitor use | 0.724 | 0.303-1.728 | 0.467 |
| Bare-metal stent implantation | 0.851 | 0.296-2.450 | 0.765 |
| Drug-eluting stent implantation | 0.995 | 0.233-4.253 | 0.994 |
| Numbers of stent implantation | 1.285 | 0.757-2.181 | 0.353 |
| Peri-procedural complications | 2.311 | 0.908-5.882 | 0.079* |
| Any dissection | 2.388 | 0.938-6.081 | 0.068* |
| Spiral dissection | 1.638 | 0.336-7.987 | 0.542 |
| Acute no-reflow after stenting | 0.988 | 0.212-4.602 | 0.988 |
| Heavy calcification | 2.026 | 0.733-5.599 | 0.173 |
| IRA lesion > 20 mm | 4.517 | 0.587-34.768 | 0.148 |
| Bifurcation lesion | 0.874 | 0.488-1.567 | 0.652 |
| Medication use at discharge | |||
| Aspirin | 0.509 | 0.054-4.758 | 0.553 |
| Beta-blocker | 0.405 | 0.159-1.035 | 0.059* |
| ACEI or ARB | 7.958 | 2.815-22.49 | < 0.001# |
* Trends toward significant associations among variables and CIAKI. # Statistical significance among variables and CIAKI. † 32 data missing for flurotime. ‡ see detailed in material and methods
ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BID, balloon inflations and deflations; CI, confidence interval; CIAKI, contrast-induced acute kidney injury; IABP, intra-aortic balloon pump; IRA, infarct-related artery; LAD, left anterior descending coronary artery; OR, odds ratio; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; TIMI flow, thrombolysis in myocardial infarction flow.
In multivariate analysis, Model 1 adjusted for confounders in univariate analysis and demonstrated significant associations between CIAKI and variables included SI > 10 (adjusted OR: 4.179, 95% CI: 1.197-14.593, p = 0.025), age (adjusted OR: 1.068, 95% CI: 1.013-1.127, p = 0.015), and ACEI/ARB use at discharge (adjusted OR: 13.27, 95% CI: 2.582-68.207, p = 0.002). BID > 9 times and SI as continuous variable was no longer associated with CIAKI in multivariable analysis. In Model 2, SI > 10 was still independently correlated with CIAKI on top of MRS (adjusted OR: 4.434, 95% CI: 1.650-11.912, p = 0.003). In Model 3, we adjusted MRS and other confounders not included in MRS. SI > 10 remained significantly associated with CIAKI (adjusted OR: 3.498, 95% CI: 1.086-11.268, p = 0.036). Adjustment in different models was shown in Table 4.
Table 4. Association among variables and CIAKI in STEMI patients undergoing primary PCI by multivariate regression analysis.
| Variables | Adjusted OR | 95% CI | p value |
| Model 1 | |||
| Age (years) | 1.055 | 1.004-1.109 | 0.033* |
| Creatinine (mg/dl) | 1.427 | 0.778-2.620 | 0.251 |
| Hemoglobin (g/dl) | 0.908 | 0.689-1.197 | 0.493 |
| Multi-vessel disease | 6.373 | 0.698-58.17 | 0.101 |
| SI > 10 | 4.179 | 1.197-14.59 | 0.025* |
| BID > 9 times | 1.846 | 0.543-6.271 | 0.326 |
| Any dissection | 1.161 | 0.322-4.185 | 0.82 |
| IABP use | 1.748 | 0.497-6.145 | 0.384 |
| Beta-blocker | 1.539 | 0.407-5.812 | 0.525 |
| ACEI or ARB | 13.27 | 2.582-68.21 | 0.002* |
| Model 2 | |||
| SI > 10 | 4.434 | 1.650-11.91 | 0.003* |
| MRS | 1.243 | 1.113-1.387 | < 0.001* |
| Model 3 | |||
| SI > 10 | 3.498 | 1.086-11.27 | 0.036* |
| MRS | 1.172 | 1.026-1.339 | 0.020* |
| Multi-vessel disease | 5.851 | 0.672-50.94 | 0.11 |
| BID > 9 times | 1.866 | 0.600-5.804 | 0.281 |
| Any dissection | 1.123 | 0.332-3.800 | 0.852 |
| Beta-blocker | 1.781 | 0.493-6.430 | 0.379 |
| ACEI or ARB | 9.864 | 2.292-42.46 | < 0.001* |
* Statistical significance among variables and CIAKI.
ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BID, balloon inflations and deflations; CI, confidence interval; CIAKI, contrast-induced acute kidney injury; IABP, intra-aortic balloon pump; MRS, Mehran risk score; OR, odds ratio; PCI, percutaneous coronary intervention; SI, SYNTAX score of infarct-related artery; STEMI, ST-segment elevation myocardial infarction.
We also performed a subgroup analysis involving the following: patients with normal kidney function (serum creatinine of 1.5 mg/dl or less) vs. patients with kidney dysfunction (serum creatinine more than 1.5 mg/dl); patients with simple vascular lesion (SI of 10 or less) vs. patients with complex vascular lesion (SI > 10); and patients with cardiogenic shock vs. those patients without cardiogenic shock (shown in supplemental Table 1-3). A subgroup analysis showed that BID > 9 times was associated with increased risks of incident CIAKI in the patients of 75 years old or less (crude OR: 7.54, 95% CI: 1.93-29.41, p < 0.001), male (crude OR: 5.71, 95% CI: 1.83-17.87, p < 0.001), low body mass index less than 25 kg/m2 (crude OR: 23.47, 95% CI: 2.7-204, p < 0.001), cardiogenic shock (crude OR: 14.63, 95% CI: 1.83-11.43, p = 0.01), and use of IABP (crude OR: 6.86, 95% CI: 1.59-29.62, p = 0.01) in the STEMI patients undergoing primary PCI at MRS > 5 (shown in Figure 2). In the subgroups of patients with normal kidney function and patients with complex vascular lesion, the risk of CIAKI were not significantly greater in the BID > 9 times group than the BID ≤ 9 times group (in patients with normal kidney function: crude rate of CIAKI: 4.5% vs. 14%, p = 0.052 and crude OR: 2.395, 95% CI: 0.792-7.242; in patients with complex vascular lesion: crude rate of CIAKI: 27.3% vs. 14.6%, p = 0.246 and crude OR: 2.187, 95% CI: 0.688-6.952).
Supplemental Table 3. Subgroup analysis of STEMI patients with vs. without cardiogenic shock.
| Variables | With cardiogenic shock | Without cardiogenic shock | ||||
| BID ≤ 9 times (N = 105) | BID > 9 times (N = 55) | p | BID ≤ 9 times (N = 34) | BID > 9 times (N = 12) | p | |
| Age (years) | 68 (55-80) | 67 (59-77) | 0.931 | 59 (53-67) | 60 (51-72) | 0.871 |
| Body mass index (kg/m2) | 24.8 (22.2-27.2) | 23.8 (22.0-26.6) | 0.363 | 24.2 (22.7-27.4) | 24.5 (22.0-26.4) | 0.797 |
| Creatinine (mg/dl) | 1.1 (0.8-1.4) | 1.1 (0.8-1.7) | 0.698 | 1.3 (0.9-1.6) | 1.2 (0.9-1.6) | 0.774 |
| Hemoglobin (g/dl) | 13.8 (12.0-15.3) | 13.7 (11.7-15.2) | 0.748 | 14.9 (13.0-15.9) | 13.6 (10.3-15.3) | 0.118 |
| CAD risk factors | ||||||
| Male | 31 (29.5) | 18 (32.7) | 0.720 | 3 (8.8) | 4 (33.3) | 0.064 |
| Current/past smoker | 43 (41.0) | 30 (54.5) | 0.132 | 23 (67.6) | 3 (25.0) | 0.017 |
| Hypertension | 75 (71.4) | 41 (74.5) | 0.852 | 14 (41.2) | 3 (25.0) | 0.489 |
| Diabetes | 53 (50.5) | 26 (47.3) | 0.739 | 24 (70.6) | 5 (41.7) | 0.093 |
| Hyperlipidemia | 33 (31.4) | 12 (21.8) | 0.266 | 8 (23.5) | 2 (16.7) | 1.000 |
| Known CAD | 16 (15.2) | 9 (16.4) | 1.000 | 4 (11.8) | 3 (25.0) | 0.355 |
| Previous MI | 4 (3.8) | 3 (5.5) | 0.699 | 2 (5.9) | 1 (8.3) | 1.000 |
| Ischemic stroke | 11 (10.5) | 6 (10.9) | 1.000 | 4 (11.8) | 2 (16.7) | 0.644 |
| Killip class | ||||||
| I | 55 (52.4) | 23 (41.8) | 0.245 | 0 (0) | 0 (0) | - |
| II | 41 (39.0) | 22 (40.0) | 1.000 | 0 (0) | 0 (0) | - |
| III | 10 (9.5) | 9 (16.4) | 0.120 | 0 (0) | 0 (0) | - |
| IV | 0 (0) | 0 (0) | - | 34 (100.0) | 12 (100.0) | - |
| Mehran risk score | ||||||
| Hypotension | 0 (0) | 0 (0) | - | 34 (100.0) | 12 (100.0) | - |
| IABP support | 27 (25.7) | 17 (30.9) | 0.576 | 22 (64.7) | 7 (58.3) | 0.737 |
| Congestive heart failure | 7 (6.7) | 9 (16.4) | 0.093 | 0 (0.0) | 0 (0.0)0 | - |
| Age > 75 (years) | 39 (37.1) | 19 (34.5) | 0.863 | 4 (11.8) | 2 (16.7) | 0.644 |
| Anemia | 35 (33.3) | 19 (34.5) | 1.000 | 7 (20.6) | 4 (33.3) | 0.441 |
| Procedural characteristics | ||||||
| Numbers of BID performed | 6 (4-7) | 13 (12-17)0 | < 0.001 | 5 (4-7) | 16 (12-19) | < 0.001 |
| Contrast volume (ml) | 155 (150-200) | 200 (175-265) | < 0.001 | 180 (150-200) | 260 (165-280) | 0.022 |
| Fluoroscopy times (min)* | 10.8 (8.8-13.7) | 17.6 (13.4-25.4) | < 0.001 | 11.2 (8.4-16.0) | 20.6 (13.3-25.8) | 0.018 |
| Door-to-balloon time (min) | 74 (60-110) | 77 (63-110) | 0.519 | 77 (60-96) | 112 (85-141) | 0.040 |
| Trans-femoral approach | 96 (91.4) | 44 (80.0) | 0.046 | 33 (97.1) | 11 (91.7) | 0.458 |
| Thrombus aspiration | 66 (62.9) | 25 (45.5) | 0.044 | 14 (41.2) | 7 (58.3) | 0.335 |
| Glycoprotein IIb/IIIa inhibitor | 65 (61.9) | 31 (56.4) | 0.503 | 18 (52.9) | 8 (66.7) | 0.509 |
| IABP support | 10 (9.5) | 5 (9.1) | 0.701 | 10 (29.4) | 5 (41.7) | 0.488 |
| Multiple-vessel disease | 69 (65.7) | 48 (87.3) | 0.004 | 24 (70.6) | 9 (75.0) | 1.000 |
| Infarct-related artery | ||||||
| LAD | 51 (48.6) | 24 (43.6) | 0.618 | 16 (47.1) | 5 (41.7) | 1.000 |
| Non-LAD | 0 (0) | 0 (0) | - | 0 (0) | 0 (0) | - |
| LM | 1 (1.0) | 0 (0) | 1.000 | 0 (0) | 1 (8.3) | 0.261 |
| Stent implantation | 88 (83.8) | 53 (96.4) | 0.021 | 30 (88.2) | 11 (91.7) | 1.000 |
| Bare-metal stent | 83 (79.0) | 45 (81.8) | 0.836 | 27 (79.4) | 11 (91.7) | 0.660 |
| Drug-eluting stent | 5 (4.8) | 9 (16.4) | 0.035 | 3 (8.8) | 0 (0.0) | 0.557 |
| Number of stent implantations | ||||||
| 1 | 69 (65.7) | 18 (32.7) | < 0.001 | 26 (76.5) | 4 (33.3) | 0.013 |
| 2 | 18 (17.1) | 23 (41.8) | < 0.001 | 4 (11.8) | 4 (33.3) | 0.178 |
| 3 | 1 (1.0) | 10 (18.2) | < 0.001 | 0 (0) | 3 (25.0) | 0.014 |
| 4 | 0 (0) | 3 (5.5) | 0.039 | 0 (0) | 0 (0) | - |
| Initial TIMI flow | ||||||
| 0 | 80 (76.2) | 30 (54.5) | 0.007 | 26 (76.5) | 9 (75.0) | 1.000 |
| 1 | 7 (6.7) | 5 (9.1) | 0.753 | 1 (2.9) | 2 (16.7) | 0.162 |
| 2~3 | 18 (17.1) | 20 (36.4) | 0.010 | 6 (17.6) | 1 (8.3) | 0.657 |
| Final TIMI flow | ||||||
| 0 | 2 (1.9) | 0 (0) | 0.546 | 1 (2.9) | 0 (0) | 1.000 |
| 1 | 2 (1.9) | 0 (0) | 0.546 | 0 (0) | 0 (0) | 1.000 |
| 2~3 | 101 (96.2) | 55 (100.0) | 0.300 | 2 (5.9) | 0 (0) | 1.000 |
| PCI to non-IRA | 2 (1.9) | 2 (3.6) | 0.608 | 1 (2.9) | 1 (8.3) | 0.467 |
| Heavy calcification of IRA | 29 (27.6) | 12 (21.8) | 1.000 | 4 (11.8) | 0 (0.0) | 0.561 |
| IRA lesion > 20mm | 85 (81.0) | 48 (87.3) | 0.378 | 30 (88.2) | 10 (83.3) | 0.598 |
| Bifurcation lesion of IRA | 68 (64.8) | 37 (67.3) | 0.642 | 21 (61.8) | 9 (75.0) | 0.330 |
| Side branch > 1.5mm | 40 (38.1) | 25 (45.5) | 14 (41.2) | 8 (66.7) | ||
| Side branch < 1.5mm | 28 (26.7) | 12 (21.8) | 7 (20.6) | 1 (8.3) | ||
| Periprocedural complications | ||||||
| Any dissection | 54 (51.4) | 27 (49.1) | 0.868 | 15 (44.1) | 9 (75.0) | 0.101 |
| Type D dissection | 4 (3.8) | 5 (9.1) | 0.277 | 3 (8.8) | 0 (0.0) | 0.553 |
| Type F dissection | 11 (10.5) | 5 (9.1) | 1.000 | 32 (94.1) | 11 (91.7) | 0.467 |
| Outcome | ||||||
| CIAKI | 8 (7.6) | 8 (14.5) | 0.176 | 2 (5.9) | 5 (41.7) | 0.009 |
Figure 2.
Relative risks of CIAKI in the BID > 9 times vs. ≤ 9 times groups in different subgroups. The horizontal axis represented an odds ratio for incident CIAKI. BID, balloon inflations and deflations; CIAKI, contrast-induced acute kidney injury.
DISCUSSIONS
The main findings of the present study included that: 1) more balloon inflation (i.e. BID > 9 times during PCI) was associated with risk of CIAKI in univariate analysis, although the association disappeared after adjustment for potential confounders; 2) an independent predictor of development of CIAKI was vascular complexity rather than the number of BIDs performed or TIMI flow or periprocedural complications; and 3) ACEI or ARB was associated with an increased incidence of CIAKI in STEMI patients with intermediate risks of CIAKI.
In the present study, BID > 9 times was significantly associated with increased rates of CIAKI in univariate analysis but the significance disappeared after confounders were adjusted. This indicated that vascular complexity behind the number of BIDs might be the true culprit of CIAKI. In contrast to our study, Whittaker et al. suggested that BID ≥ 4 times in STEMI patients were associated with preserved estimated glomerular filtration rate.9 The conflicting results might be partly explained by two main reasons. First, we enrolled STEMI patients with intermediate risks of CIAKI, whereas Whittaker et al. selected those study subjects with low risks. Therefore, the incidence of CIAKI was 11.2% in our study while no CIAKI developed in their study. Second, we enrolled consecutive patients, even including patients with cardiogenic shock and multi-vessel disease; on the other hand, Whittaker et al. selected those with single-vessel occlusion. We believed that a difference in baseline CIAKI risks and vascular complexity of study population results in the opposed effect of the number of BIDs performed.
The phenomenon of BIDs for renal protection was reported in patients with non ST-segment elevation myocardial infarction (NSTEMI). Deftereos et al. had designed a well-controlled randomized trial to test the hypothesis of renal protection between BID and CIAKI.10 To induce the effect of RIPC, they used an additional four cycles of intermittent BID composed of inflation for 30 sec and deflation for another 30 sec immediately after PCI to the presumed culprit lesion of myocardial infarction. CIAKI was significantly lower in the RIPC group than in the control group (12.4% vs. 29.5%, p = 0.002). RIPC was an independent negative predictor of CIAKI with adjustment for age, body mass index, baseline EGFR, and contrast volume use (adjusted OR = 0.23, 95% CI: 0.11 to 0.50; p < 0.001). The vessel number was no statistically different between two groups. However, the vascular complexity was not taken into the statistical adjustment.
The relationship between SYNTAX score and CIAKI had been investigated in patients with NSTEMI or unstable angina. Madhavan et al. demonstrated that the highest tertile (> 12 within their study) of SYNTAX score was associated with increased rates of CIAKI as well as in-hospital, 30-day and 1-year mortality in multivariate analyses.19 Although SYNTAX score was used as an independent predictor of acute no-reflow or 1-year all-cause mortality in STEMI patients, the association between SYNTAX score and CIAKI was not yet extensively explored in these populations.20,21 Our study was the first to extend this parameter (SI) to STEMI, which demonstrated that SI > 10 was independently associated with the development of CIAKI on top of MRS.
Most studies discussing STEMI patients have focused on the association between IPC and infarct myocardial size rather than RIPC and CIAKI. In Hahn et al.’s study, IPC was induced by 4 cycles of repetitive coronary balloon inflations for 1-minute and deflations for the other 1-minute at the culprit lesion, using low-pressure coronary balloon, immediately after restoration of coronary flow. This largest prospective randomized control trial showed that IPC did not improve myocardial reperfusion in STEMI patients under the current standards of practice, with respect to all possible confounders.22 Theoretically, IPC using alternative coronary balloon inflations and deflations may induce coronary micro-embolism and coronary artery dissection. Hence, using a blood pressure cuff on an upper arm emerged as a safe procedure of remote ischemic pre-conditioning (RIPreC) in patients undergoing elective PCI.23 In the CRISP study, patients in the intervention group received 3 cycles of 5-minute inflations of a blood pressure cuff to 200 mm Hg around the non-dominant upper arm, followed by 5-minute deflations before PCI. This study demonstrated that patients receiving RIPreC vs. shamed procedures significantly reduced ischemic chest discomfort during PCI and attenuated cardiac troponin-I release after PCI than those who received a shamed procedure. Furthermore, the study showed that RIPreC was associated with better long term outcomes during 6-year follow-up.24 Unfortunately, the beneficial effect of RIPreC could not be translated to RIPC in patients with stable or unstable angina undergoing elective PCI.25 In the Carrasco-Chinchilla study, patients in the RIPC group underwent similar procedures to RIPreC of the CRISP study except that it was performed 5 min after the last stent implantation or balloon post-dilation. Contrary to the results of the CRISP stent study, the peak level of cardiac troponin I at 24-hour and mortality at 1-year were not significantly different between the RIPC and the control group. In the subgroup of diabetic patients, RIPC was associated with more periprocedural myocardial infarction.25 Lavi et al. investigated the effect of RIPC by a blood pressure cuff placed on the left arm or thigh in patients with stable angina or unstable angina and negative cardiac troponin T at baseline.26 The inflation cuff pressure was more than 200 mm Hg in the arm, 300 mm Hg in the thigh, or more than 50 mm Hg above systolic blood pressure. The RIPC cycle was performed with cuff inflation for 5 minutes, followed by 5-minute deflations, and repeated for a total of 3 cycles. They suggested that RIPC applied to the arm or thigh during non-urgent PCI did not reduce periprocedural myocardial injury.26 In the Er et al. study, RIPreC consisted of 4 cycles of 5-minute inflations and 5-minute deflations, with a standard blood pressure cuff placed on an upper-arm by inflating additional 50 mm Hg over individual’s systolic blood pressure before coronary angiography. RIPreC was strongly associated with prevention from CIAKI. The peak level of urinary neutrophil gelatinase-associated lipocalin and serum cystatin C were also significantly lower in the RIPreC group than in the control group.27 Despite the conflicting results among the above studies, several key points of successful ischemic conditioning may be postulated. First, the timing of conditioning is a critical point. Renal protection was disclosed in the pre-conditioning studies rather than in the post-conditioning studies in patients with stable and unstable angina.23,25,27 Although IPC was usually performed immediately after restoration of coronary activity in conditioning the heart, the optimal time between the first blood pressure cuff inflation and the last coronary stenting or balloon dilation remained controversial in the circumstance of RIPC. Further studies are necessary to investigate the association between time interval of RIPC and the last stenting or balloon dilation. Second, our study showed that RIPC "to the heart" had a harmful effect on renal function in contrast to results in other studies, which showed beneficial or neutral renal protection effects with conditioning of the extremities.9,10 Given that the "possible" beneficial effect on renal function by RIPC may be "compensated" by intra-coronary BID related "coronary" complications, we suggest that an extremity rather than the heart should be "conditioned" during the RIPC. Third, it is not clear how many cycles and how much time should be devoted to ischemia/reperfusion. The optimal protocol of RIPC, such as the number of cycles and the time interval of ischemia and reperfusion has not been established. According to a recent meta-analysis, 5-min stimulation is essential to elicit the effect of conditioning.28 The meta-analysis suggested that 3-4 cycles of conditioning was widely used in most studies, although only one study reported one cycle of conditioning as effective as 3-4 cycle of conditioning. It is unknown if more cycles of conditioning are associated with additional renal protection. A large-scale study is needed to test the correlation between cycles of RIPC and prevention of CIAKI.
Several limitations of our study should be emphasized. This was a retrospective study with a rather small and heterogeneous population, while it reflects clinical practice in Taiwan. Some possible confounders were not recorded such as index ischemic time and duration of each BID, pre-use of nephrotoxic agents (ex. non-steroid anti-inflammatory drug). The CIAKI prevention strategy, e.g., N-acetylcysteine, hydration, or sodium bicarbonate administration, was not well-standardized in such emergent condition. A large-scaled prospective study is warranted to further elucidate the renoprotective effect of balloon inflation and deflation times in different target populations.
CONCLUSIONS
Higher balloon inflation and deflation times (> 9) was associated with increased rates of CIAKI on top of Mehran risk score. After adjustment, vascular complexity of IRA was the major determinant of the development of CIAKI after primary percutaneous coronary intervention in STEMI patients.
Acknowledgments
We thank Yung-Cheng Chen, Yung-Chu Tsai and the Cath Lab of Far Eastern Memorial Hospital for the assistance. This work was supported in part by grant FEMH-2013-HHC-002, FEMH-2014-HHC-002 from Far Eastern Memorial Hospital, and MOST 103-2325-B-418-001 from the Ministry of Science Technology of Taiwan.
REFERENCES
- 1.Rihal CS, Textor SC, Grill DE, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002;105:2259–2264. doi: 10.1161/01.cir.0000016043.87291.33. [DOI] [PubMed] [Google Scholar]
- 2.Lindsay J, Apple S, Pinnow EE, et al. Percutaneous coronary intervention-associated nephropathy foreshadows increased risk of late adverse events in patients with normal baseline serum creatinine. Catheter Cardiovasc Interv. 2003;59:338–343. doi: 10.1002/ccd.10534. [DOI] [PubMed] [Google Scholar]
- 3.Gupta R, Gurm HS, Bhatt DL, et al. Renal failure after percutaneous coronary intervention is associated with high mortality. Catheter Cardiovasc Interv. 2005;64:442–448. doi: 10.1002/ccd.20316. [DOI] [PubMed] [Google Scholar]
- 4.Roghi A, Savonitto S, Cavallini C, et al. Impact of acute renal failure following percutaneous coronary intervention on long-term mortality. J Cardiovasc Med. 2008;9:375–381. doi: 10.2459/JCM.0b013e3282eee979. [DOI] [PubMed] [Google Scholar]
- 5.Kim MJ, Choi HS, Oh SH, et al. Impact of acute kidney injury on clinical outcomes after ST elevation acute myocardial infarction. Yonsei Med J. 2011;52:603–609. doi: 10.3349/ymj.2011.52.4.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Kume K, Yasuoka Y, Adachi H, et al. Impact of contrast-induced acute kidney injury on outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Cardiovasc Revasc Med. 2013;14:253–257. doi: 10.1016/j.carrev.2013.07.009. [DOI] [PubMed] [Google Scholar]
- 7.Skyschally A, van Caster P, Iliodromitis EK, et al. Ischemic postconditioning: experimental models and protocol algorithms. Basic Res Cardiol. 2009;104:469–483. doi: 10.1007/s00395-009-0040-4. [DOI] [PubMed] [Google Scholar]
- 8.Schevchuck A, Laskey WK. Ischemic conditioning as an adjunct to percutaneous coronary intervention. Circ Cardiovasc Interv. 2013;6:484–492. doi: 10.1161/CIRCINTERVENTIONS.113.000146. [DOI] [PubMed] [Google Scholar]
- 9.Whittaker P, Przyklenk K. Remote-conditioning ischemia provides a potential approach to mitigate contrast medium-induced reduction in kidney function: a retrospective observational cohort study. Cardiology. 2011;119:145–150. doi: 10.1159/000330930. [DOI] [PubMed] [Google Scholar]
- 10.Deftereos S, Giannopoulos G, Tzalamouras V, et al. Renoprotective effect of remote ischemic post-conditioning by intermittent balloon inflations in patients undergoing percutaneous coronary intervention. J Am Coll Cardiol. 2013;61:1949–1955. doi: 10.1016/j.jacc.2013.02.023. [DOI] [PubMed] [Google Scholar]
- 11.Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360:961–972. doi: 10.1056/NEJMoa0804626. [DOI] [PubMed] [Google Scholar]
- 12.O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the American College of Emergency Physicians and Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv. 2013;82:E1–E27. doi: 10.1002/ccd.24776. [DOI] [PubMed] [Google Scholar]
- 13.Liu CW, Liao PC, Chen KC, et al. Baseline hemoglobin levels associated with one-year mortality in ST-segment elevation myocardial infarction patients. Acta Cardiol Sin. 2016;32:656–666. doi: 10.6515/ACS20160106A. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Li YH, Yeh HI, Tsai CT, et al. 2012 guidelines of the Taiwan Society of Cardiology (TSOC) for the management of ST-segment elevation myocardial infarction. Acta Cardiol Sin. 2012;28:63–89. [Google Scholar]
- 15.Huang CC, Chen JW. Contemporary management of coronary artery disease and acute coronary syndrome in patients with chronic kidney disease and end-stage renal disease. Acta Cardiol Sin. 2013;29:132–141. [PMC free article] [PubMed] [Google Scholar]
- 16.Li YH, Hsieh IC, Shyu KG, Kuo FY. What could be changed in the 2012 Taiwan ST-segment elevation myocardial infarction guideline? Acta Cardiol Sin. 2014;30:360–364. [PMC free article] [PubMed] [Google Scholar]
- 17.Chang CC, Hsu CY, Huang PH, et al. Association of serum bilirubin with SYNTAX score and future cardiovascular events in patients undergoing coronary intervention. Acta Cardiol Sin. 2016;32:412–419. doi: 10.6515/ACS20150708C. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Mehran R, Aymong ED, Nikolsky E, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol. 2004;44:1393–1399. doi: 10.1016/j.jacc.2004.06.068. [DOI] [PubMed] [Google Scholar]
- 19.Madhavan MV, Genereux P, Rubin J, et al. Usefulness of the SYNTAX score to predict acute kidney injury after percutaneous coronary intervention (from the Acute Catheterization and Urgent Intervention Triage Strategy Trial). Am J Cardiol. 2014;113:1331–1337. doi: 10.1016/j.amjcard.2013.12.041. [DOI] [PubMed] [Google Scholar]
- 20.Sahin DY, Gur M, Elbasan Z, et al. SYNTAX score is a predictor of angiographic no-reflow in patients with ST-elevation myocardial infarction treated with a primary percutaneous coronary intervention. Coron Artery Dis. 2013;24:148–153. doi: 10.1097/MCA.0b013e32835c4719. [DOI] [PubMed] [Google Scholar]
- 21.Su MI, Tsai CT, Yeh HI, Chen CY. The impact of SYNTAX score of non-infarct-related artery on long-term outcome among patients with acute ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. PloS One. 2014;9:e109828. doi: 10.1371/journal.pone.0109828. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Hahn JY, Yu CW, Park HS, et al. Long-term effects of ischemic postconditioning on clinical outcomes: 1-year follow-up of the POST randomized trial. Am Heart J. 2015;169:639–646. doi: 10.1016/j.ahj.2015.01.015. [DOI] [PubMed] [Google Scholar]
- 23.Hoole SP, Heck PM, Sharples L, et al. Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial. Circulation. 2009;119:820–827. doi: 10.1161/CIRCULATIONAHA.108.809723. [DOI] [PubMed] [Google Scholar]
- 24.Davies WR, Brown AJ, Watson W, et al. Remote ischemic preconditioning improves outcome at 6 years after elective percutaneous coronary intervention: the CRISP stent trial long-term follow-up. Circ Cardiovasc Interv. 2013;6:246–251. doi: 10.1161/CIRCINTERVENTIONS.112.000184. [DOI] [PubMed] [Google Scholar]
- 25.Carrasco-Chinchilla F, Munoz-Garcia AJ, Dominguez-Franco A, et al. Remote ischaemic postconditioning: does it protect against ischaemic damage in percutaneous coronary revascularisation? Randomised placebo-controlled clinical trial. Heart. 2013;99:1431–1437. doi: 10.1136/heartjnl-2013-304172. [DOI] [PubMed] [Google Scholar]
- 26.Lavi R, D'Alfonso S, Diamantouros P, et al. Response to letter regarding article, "Remote ischemic postconditioning during percutaneous coronary interventions: remote ischemic postconditioning-percutaneous coronary intervention randomized trial". Circ Cardiovasc Interv. 2014;7:423. doi: 10.1161/CIRCINTERVENTIONS.114.001591. [DOI] [PubMed] [Google Scholar]
- 27.Er F, Nia AM, Dopp H, et al. Ischemic preconditioning for prevention of contrast medium-induced nephropathy: randomized pilot RenPro Trial (Renal Protection Trial). Circulation. 2012;126:296–303. doi: 10.1161/CIRCULATIONAHA.112.096370. [DOI] [PubMed] [Google Scholar]
- 28.Pei H, Wu Y, Wei Y, et al. Remote ischemic preconditioning reduces perioperative cardiac and renal events in patients undergoing elective coronary intervention: a meta-analysis of 11 randomized trials. PloS one. 2014;9:e115500. doi: 10.1371/journal.pone.0115500. [DOI] [PMC free article] [PubMed] [Google Scholar]