Author + information
- Received April 15, 2008
- Revision received July 16, 2008
- Accepted July 30, 2008
- Published online February 1, 2009.
- Tadayuki Uetani, MD, PhD⁎,⁎ (, )
- Tetsuya Amano, MD, PhD⁎,
- Soichiro Kumagai, MD⁎,
- Hirohiko Ando, MD⁎,
- Kiminobu Yokoi, MD⁎,
- Tomohiro Yoshida, MD⁎,
- Bunichi Kato, MD, PhD⁎,
- Masataka Kato, MD⁎,
- Nobuyuki Marui, MD, PhD⁎,
- Michio Nanki, MD, PhD⁎,
- Tatsuaki Matsubara, MD, PhD†,
- Hideki Ishii, MD, PhD‡,
- Hideo Izawa, MD, PhD‡ and
- Toyoaki Murohara, MD, PhD‡
- ↵⁎Reprint requests and correspondence:
Dr. Tadayuki Uetani, Department of Cardiology, Chubu Rosai Hospital, 1-10-6, Komei, Minato-ku, Nagoya, Japan
Objectives With an intracoronary electrocardiogram (IcECG) recording with insulated polymer-coated guidewire without balloon catheter, we sought to examine the association between ST-segment elevation in the IcECG after elective stenting and myocardial injury.
Background An IcECG is a sensitive method to detect local myocardial ischemia. Occasionally, persistent ST-segment elevation in the IcECG was recorded after successful coronary intervention. Conventionally IcECG was recorded with a guidewire and over-the-wire system.
Methods Patients who underwent elective stenting were enrolled (n = 339). The IcECG both at baseline and after procedure were obtained with a guidewire with an insulating coated shaft suitable for IcECG recording. The presence of chest pain after percutaneous coronary intervention was recorded. Cardiac biomarkers were examined 18 h after the procedure.
Results The ST-segment elevation in the IcECG after procedure was recorded in 65 patients, and no change was recorded in 274 patients. Troponin-T, creatine phosphokinase, and creatine kinase MB isoform after the procedure were significantly higher in patients with post-procedural ST-segment elevation in the IcECG than patients without ST-segment elevation. Multivariate analysis demonstrated that ST-segment elevation in the IcECG is an independent predictor of post-procedural myocardial injury. The incidence of ST-segment elevation in the IcECG was significantly higher in patients with post-procedural chest pain than patients without chest pain (p < 0.001).
Conclusions We demonstrated a facile method to record IcECG with a guidewire with a polymer-coated shaft. The IcECG is a useful method for predicting post-procedural myocardial injuries.
Post-procedural myocardial injury after apparent uncomplicated percutaneous coronary intervention (PCI) is not uncommon (1–3). Previously subclinical creatine kinase-MB (CK-MB) elevation in 5% to 30% of patients after successful PCI was reported. Some biochemical markers are more sensitive and specific in detecting myocardial damages.
Formerly, modest elevations of cardiac enzymes after successful PCI were considered relatively benign, and clinical implications of this phenomenon were not fully investigated. Recently, some trials demonstrated that elevated cardiac biomarkers after apparently successful PCI were associated with increased risks of adverse cardiac events (4–6).
Intracoronary electrocardiogram (IcECG) with a guidewire as a unipolar electrode represents local epicardial ECG. Unipolar IcECG seemed to be more sensitive than surface ECG for detecting local ischemia during coronary interventions (7,8). Some studies demonstrated IcECG can be used to assess myocardial viability in stable angina and acute myocardial infarctions (9,10).
Previously, an over-the-wire or monorail catheter had to be crossed at the target lesion to provide insulation of the guidewire in the part proximal to the stenosis during IcECG recording (9). However, in a case of severe stenosis or coronary occlusion, severe ischemic changes of IcECG might occur if a balloon catheter is wedged into the stenosis. Therefore, we recorded the IcECG with a guidewire with an insulated polymer cover to overcome these disadvantages caused by usage of the over-the-wire catheters.
In most cases, ST-segment elevation appeared during balloon inflation and resolved promptly after deflation of the balloons. Previous studies have reported that persistent ST-segment elevation after the balloon deflation was observed in some cases (9). In our own experience, persistent ST-segment elevation in the IcECG compared with the baseline IcECG was recorded occasionally after successful PCI without surface ECG abnormality. Thus, we postulate persistent ST-segment elevation in the IcECG reflected local myocardial injury after the PCI. Therefore, we designed this study to evaluate the relation between post-procedural ST-segment elevation in the IcECG and the elevation of biochemical markers of myocardial injury after elective PCI compared with surface ECG.
From September 2004 to December 2006, 339 consecutive patients who underwent apparently successful elective coronary stent implantations in Chubu Rosai Hospital, Nagoya, Japan, were enrolled in this study, which was approved by the ethics committee of the hospital. All had angina, documented myocardial ischemia, or both and signed informed consent for the study. The exclusion criteria of this study were patients with: 1) emergency coronary angioplasty within 24 h of onset; 2) elevated pre-procedural cardiac biomarker; 3) active congestive heart failure; 4) severe lesion characteristics not suitable for soft-tip guidewire; 5) angioplasty with debulking device (directional coronary atherectomy or rotational atherectomy); 6) Thrombolysis In Myocardial Infarction (TIMI) flow grade 1 to 2 of target vessel at the end of procedure; and 7) multivessel stenting in a single procedure. This study was approved by the ethics committee of our hospital.
The study protocol was as follows. First, we recorded the baseline surface ECG and IcECG after positioning the guidewire in the distal part of a target vessel. Then coronary stent implantation was performed after the pre-procedural coronary angiography and intravascular ultrasound (IVUS) recording. We also recorded post-procedural coronary angiography and IVUS. After confirmation of an uncomplicated PCI, we recorded the final surface ECG and IcECG. Finally, we obtained blood samples at approximately 18 h after the PCI to evaluate cardiac biomarkers.
Angiography and IVUS were evaluated by an independent investigator not involved in the procedures who is unaware of the final outcomes. A computerized quantitative analysis system (QCA-CMS system version 18.104.22.168, MEDIS, Leiden, the Netherlands) was employed with the guiding catheter for calibration. The IVUS studies were performed with a mechanical sector scanner (Atlantis SR Pro, Boston Scientific Corp., Natick, Massachusetts) and motorized transducer pullback system (0.5 mm/s).
All patients underwent elective coronary stent implantation with or without balloon pre-dilation. All patients received antiplatelet agents, for at least 24 h before the procedure. Furthermore, 10,000 IU of heparin was administered before the procedure, and an additional bolus of 1,000 to 2,000 IU was given every hour if the procedure lasted for more than 1 h. Patients without contraindication received ticlopidine (200 mg b.i.d.). No patient received glycoprotein IIb/IIIa receptor inhibitor, which is not approved in Japan. All procedures were performed with 6- to 8-F guiding catheters by either a transradial or transfemoral approach. Successful PCI defined as <50% residual stenosis with final TIMI flow grade 3 was performed in all the enrolled patients. Staff nurses in the catheterization laboratory who were independent of this study routinely recorded the presence or absence of chest pain after the PCI in all patients. Post-procedural chest pain was defined as varying degrees of typical or atypical chest pain at the end of PCI procedures.
A 0.014-inch diameter guidewire (Hi-Torque Balance Middle Weight-Universal, Abbott Vascular; Santa Clara, California) was used. The proximal shaft of this guidewire was coated with an insulated polymer cover and a distal uninsulated component was used as a unipolar electrode. The uninsulated tip of the guidewire was placed at the distal epicardial position of the target lesion. The uninsulated proximal end was connected to the chest lead terminal (V1 lead) of RMC-3100 (Nihon Kohden, Tokyo, Japan). During IcECG recording, limb leads and chest leads (V2 to V6) of surface ECG were recorded simultaneously.
Intracoronary and surface ECG were calibrated (10 mm = 1 mV) and recorded simultaneously. Baseline IcECG was recorded before usage of IVUS catheters, balloon catheters, and coronary stents crossing of target lesion. At the end of PCI, the guidewire was placed in the same position as the baseline IcECG, and the final IcECG was recorded.
The IcECG waveforms of the left anterior descending coronary artery with conventional uninsulated guidewire with and without over-the-wire catheter (bare wire) are illustrated in Figures 1A and 1B. These waveforms changed, depending on the tip position of the balloon catheter. On the contrary, the waveform of IcECG with the guidewire with a polymer cover was not influenced by use or disuse of over-the-wire catheter or by tip position of the balloon catheter (Figs. 1C and 1D). No adjunctive procedure or intracoronary drug administration was done after recording the final IcECG.
Evaluation of cardiac biomarkers
Blood was sampled 18 h after the procedure. Serum troponin-T (TnT) was measured with an enzyme immunoassay kit (Roche Diagnostics, Tokyo, Japan). The detection limit of this TnT assay system is 0.03 ng/ml, and linearity is achieved from 0.1 to 2 ng/ml. A TnT level lower than 0.03 ng/ml was considered as 0 ng/ml and 0.03 to approximately 0.1 ng/ml was considered as 0.1 ng/ml. A TnT level higher than 2 ng/ml is considered as 2 ng/ml. We defined a post-procedural TnT level higher than 0.1 ng/ml, which was manufacturers' clinical cutoff value, as a post-procedural myocardial injury. The CK-MB activity was measured with an immunoinhibition assay kit (Sysmex, Kobe, Japan). Creatine phosphokinase level was assessed with the UV-rate method (Daiichi Pure Chemicals, Tokyo, Japan).
All data are indicated in mean ± SD values. Statistical analysis was conducted with Stat-View 5.0 (SAS Institute, Cary, North Carolina). A comparison of continuous variables was achieved with the unpaired Student t test or a Mann-Whitney U test. Chi-square analysis or the Fisher exact probability test was used for group comparison of categorical variables. Univariate and multivariate logistic regression analysis were constructed to evaluate the predictor of post-procedural positive TnT. Multivariate logistic regression analysis was conducted to assess the clinical, lesion, and procedural factors associated with post-procedural TnT. Variables with a significance level of <0.2 in the univariate analysis and possible confounding factors (age, coronary risk factor, history of myocardial infarction, and de novo lesion) were considered to be candidate variables for inclusion in the multivariable analysis. Differences were considered significant at p < 0.05.
Post-procedural ST-segment elevation in the IcECG
Post-procedural ST-segment elevation in the IcECG was recorded in 65 (19.2%) patients. In 59 (91%) of these patients, no surface ECG change was observed. In 6 patients, ST-segment elevation was recorded in surface and IcECG. Representative IcECG of patients with ST-segment elevation and without ST-segment elevation were shown in Figures 2 and 3.⇓
Clinical, lesion, and procedural characteristics
Demographic data of the study population are presented in Table 1. No statistically significant differences existed between the 2 groups, except that the glomerular filtration rate level of patients with ST-segment elevation in the IcECG was lower than in patients without ST-segment elevation.
Detailed lesion and procedural characteristics are presented in Table 2. Lesion lengths of patients with ST-segment elevation in the IcECG were significantly longer than patients without changes.
Post-procedural cardiac biomarkers
Cardiac biomarkers of each group were demonstrated in Figure 4. Post-procedural TnT, CK-MB, and creatine phosphokinase were significantly higher in patients with ST-segment elevation in the IcECG (0.34 ± 0.47 vs. 0.06 ± 0.09, p < 0.001, 27.7 ± 27.5 vs. 15.7 ± 13.7, p < 0.001, and 196.8 ± 240.2 vs. 90.0 ± 60.2, p < 0.001, respectively).
Association between post-procedural chest pain and ST-segment elevation in IcECG
The ST-segment elevation in the IcECG was recorded in 25 (54.3%) patients with post-procedural chest pain and in 40 (13.7%) patients without chest pain (p < 0.001). Surface ECG change was recorded in 5 (10.9%) patients with post-procedural chest pain.
Predictor of post-procedural myocardial injury
The independent predictors of positive TnT were glomerular filtration rate, lesion length, and ST-segment elevation in the IcECG in multiple logistic regression analysis (Table 3). Sensitivity, specificity, positive predictive value, and negative predictive value of ST-segment elevation in the IcECG, post-procedural chest pain, and surface ECG change for predicting post-procedural troponin elevation are shown in Table 4. Sensitivity and specificity of ST-segment elevation of IcECG were 54.9% and 92.2%, respectively. As compared with surface ECG, IcECG shows significantly higher sensitivity for positive TnT.
Angiographic and clinical outcomes
The incidence of angiographic complication, post-procedural, and the incidence of in-hospital major adverse cardiac events (defined as myocardial infarction and cardiac death) are shown in Table 5. A higher incidence of angiographic and clinical complications in patients with ST-segment elevation of IcECG was demonstrated.
In this study, we demonstrated that incidence of ST-segment elevation in the IcECG after successful elective PCI amounted to approximately 19%. We also showed the association between ST-segment elevation in the IcECG and the higher level of post-procedural cardiac biomarkers.
A previous study demonstrated that IcECG is more sensitive compared with surface ECG for detecting myocardial ischemia during the PCI procedure (7,8). The ST-segment elevation in the IcECG after balloon deflation was documented, but the actual incidences and clinical significance of this phenomenon were not well-described. In this study, we recorded post-procedural ST-segment elevation in the IcECG without surface ECG change in 17% of the study population. Conversely, change of surface ECG without ST-segment elevation in the IcECG was recorded in 3 patients (1%). The IcECG is more sensitive and specific for detection of post-procedural myocardial injury of the treated area than surface ECG.
Post-procedural myocardial injury and IcECG
Significant post-procedural myocardial injury with cardiac biomarker elevation is not uncommon after apparently successful PCI (2,11). Contrast-enhanced MRI revealed myocardial necrosis in patients with post-procedural CK-MB elevation (12). It is well-known that surface 12-lead ECG is rather insensitive for detecting minor myocardial injury. Left ventricular electromechanical mapping demonstrated evidences of electromechanical changes after successful PCI (13). We demonstrated that monitoring ST-segment changes of IcECG is a speedy and economical method for identifying risks of cardiac injuries after the PCI procedures in the catheterization laboratory.
The mechanism of myocardial injury after a successful PCI is debatable. Several factors that are related to post-procedural cardiac biomarker elevation were indicated, such as plaque burden of the target lesion, lesion length, side branch occlusion, platelet-monocyte aggregate, age, duration of balloon inflation, number of stents deployed, stent expansion adjunctive to debulking devices, and statin administration (3,14–18). These findings suggested procedure-related microembolization is an important mechanism of biomarker elevation.
Recently, remarkably low restenosis rates of drug-eluting stents were demonstrated, and usage of coronary stents rapidly increased. Coronary stents might increase risks of post-procedural myocardial injury due to side branch occlusion and distal embolism. Larger stent expansion associated with a higher level of post-procedural CK-MB suggests a trade-off between optimal stent implantation and post-procedural myocardial injury (19). Therefore distal protection devices and an aspiration system were introduced to prevent embolization during PCI for acute myocardial infarction patients or saphenous vein graft interventions (20,21). Some studies demonstrated that intravenous nicorandil administration reduced cardiac biomarker elevation after coronary stenting procedures or primary PCI (22,23). Evaluation of IcECG might provide useful information on indicating and monitoring of these interventions.
Recently Balian et al. (24) demonstrated that intracoronary ST-segment shift after a successful PCI was associated with post-procedural myocardial injury and worse clinical outcome. Our study showed results similar to this report surveyed around the same period. Additionally we also demonstrated usefulness of a polymer-covered uninsulated guidewire and association with ST-segment elevation in IcECG and persistent chest pain after the procedure.
Chest pain after successful PCI and IcECG findings
Persistent chest pain after a successful PCI was not uncommon in patients without angiographic complications. Recently, an association between post-procedural chest pain and myocardial injury with enzyme elevation after the PCI procedure was demonstrated (25). In this study, a higher incidence of ST-segment elevation in IcECG was demonstrated in patients with chest pain after PCI than in those without chest pain. An association between post-procedural chest pain and TnT elevation was also demonstrated in this study. Therefore, this finding indicated that minor myocardial injury might play an important role in the development of post-procedural chest pain.
A major limitation of this study is the fact that the definition of ST-segment elevation in the IcECG that reflects local myocardial ischemia has not been established. The shift of distal-tip position can induce an apparent change of IcECG waveform such as T-wave inversion or change of amplitude of QRS complex. Thus, we defined persistent ST-segment elevation in the IcECG as an ischemic change. However, ST-segment shifts defined as an elevation or depression of ST-segment ≥1 mm compared with the baseline allowed more sensitive identification (74% sensitivity) of post-procedural myocardial injury (24).
Glycoprotein IIb/IIIa receptor inhibitors have shown to reduce the morbidity and mortality of patients undergoing high-risk PCI (26,27). A previous study demonstrated glycoprotein IIb/IIIa receptor inhibitor administration reduced the incidence of post-procedural cardiac biomarker elevation (28). Thus, we speculated that administration of these drugs have an influence on the appearance of ST-segment elevation in the IcECG. Although many evidences support the benefit of these drugs for patients with PCI, none of the patients in this study population had been administered these drugs, because they are yet to be approved in our country.
Intracoronary ECG provides useful information predicting post-procedural myocardial injury easily and inexpensively in patients who have undergone apparently successful PCI procedures. An association between ST-segment elevation of IcECG and persistent chest pain after procedures suggested that a minor ischemic event might be a potential mechanism of persistent chest pain.
The authors would like to thank Mr. Takahiko Matsumoto, Mr. Hiroyuki Furuta, and Mr. Shinji Watanabe for their technical support of the IcECG recording and Mr. Katsu Endo (Abbott Vascular) for supplying technical information about the guidewire.
- Abbreviations and Acronyms
- creatine kinase-MB
- intracoronary electrocardiogram
- percutaneous coronary intervention
- Thrombolysis In Myocardial Infarction
- Received April 15, 2008.
- Revision received July 16, 2008.
- Accepted July 30, 2008.
- American College of Cardiology Foundation
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