Long-term Outcome of Transient, Uncomplicated In-Laboratory Coronary Artery Closure
Background Successful reversal of abrupt vessel closure without resultant major ischemic complications (death, Q-wave myocardial infarction, or coronary artery bypass graft surgery) is achieved in nearly half of all cases of abrupt vessel closure. The long-term outcome of these patients has not been previously addressed, and it is not clear whether they have a different prognosis than that of patients who have a successful procedure not associated with transient vessel closure.
Methods and Results We examined 4863 consecutive patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA). Eighty-eight patients had an uncomplicated, successfully reversed transient in-laboratory vessel closure (group 2) and were compared with 4775 patients who had a successful procedure not associated with transient in-laboratory closure (group 1). Clinical follow-up was available in 4839 patients (99.5%), with a mean duration of 41±23 months (range, 1 to 104 months). Survival analysis showed that successfully treated, uncomplicated transient vessel closure per se does not have an adverse effect on long-term prognosis (death, myocardial infarction, or coronary interventions). However, when the procedure (PTCA or DCA) was associated with an increase in creatine kinase–MB (CK-MB), there was a significant adverse effect on long-term outcome. By multivariate logistic regression, an increase in postprocedure CK-MB was the most significant correlate for cardiac death (risk ratio, 1.25; P<.0001). An increase in CK-MB was also the most important correlate for major ischemic complications (death, infarction, or coronary interventions) on follow-up (risk ratio, 1.08; P=.0005).
Conclusions Transient, uncomplicated in-laboratory vessel closure per se does not have an adverse long-term effect. However, a concomitant elevation of postprocedure cardiac enzymes has an important and significant adverse effect on long-term outcome. This study suggests that periprocedural creatine kinase isoenzyme determination in patients experiencing in-laboratory coronary closure has important prognostic implications.
Abrupt vessel closure complicates 2% to 11% of percutaneous coronary interventions and is the most common cause of major procedure-related complications, resulting in death, Q-wave infarction, or emergency coronary artery bypass graft surgery (CABG) in nearly 50% of these patients.1 2 3 4 5 6 7 8 9
Early experience showed that acute closure can be successfully managed by repeat dilatation, obviating the need for CABG in 44% to 85% of coronary occlusions.5 10 However, in nearly half of the cases of reopened abrupt closure, the procedure becomes complicated by emergency CABG, Q-wave myocardial infarction, or death, making abrupt closure the most important risk factor for percutaneous coronary interventions.4 5 8 The NHLBI Registry data also documented an additional risk of excess rates of death and CABG on follow-up of these patients compared with patients who had a successful procedure.8 Theoretically, the different long-term outcome could be related to the abrupt closure event or to the higher frequency of in-hospital ischemic complications associated with this acute event. Because this issue has not been addressed in a previous study, it remains unclear whether successfully treated, uncomplicated transient in-laboratory closure in particular should be considered a complication of coronary interventions. Moreover, little is known about the outcome of abrupt closure that is quickly and successfully reversed in the catheterization laboratory. The aim of the present study was to evaluate the long-term outcome of successfully treated, transient in-laboratory vessel closure and to address whether transient, uncomplicated in-laboratory closure predicts a worse long-term outcome compared with a successful procedure.
Study participants were all patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA) at The Cleveland Clinic Foundation between July 1983 and December 1991. Patients with acute myocardial infarction within 36 hours or those undergoing a salvage atherectomy or intracoronary stenting for a failed procedure were excluded from this analysis. All patients gave informed consent before the procedure. Some patients in this cohort were described in a previous study that showed that minor elevations of creatine kinase (CK) (<360 IU/L) were associated with increased cardiac mortality on follow-up.11
During the study period, 159 patients (3%) had abrupt in-laboratory vessel closure. Seventy-one patients (45%) with abrupt closure were excluded because of the occurrence of one or more ischemic complications (death, Q-wave infarction, or CABG) (58 patients) or the inability to establish TIMI grade 3 flow (13 patients). These patients have been shown in previous studies to have worse short- and long-term outcomes than patients who had a successful procedure not associated with abrupt closure.4 5 8
Eighty-eight patients (55%) had successful reversal of the abrupt closure and made up one study group (group 2). This group was compared with 4775 consecutive patients who had a successful procedure with no abrupt in-laboratory vessel closure during the same time period (group 1).
Techniques of PTCA and DCA
The coronary angioplasty and atherectomy procedures were performed as described in detail elsewhere.7 12 All patients received aspirin and a calcium channel blocker. Intravenous heparin (10 000 to 15 000 U) was administered at the beginning of the procedure, followed by additional boluses as needed. After completion of the procedure, the patients were routinely observed for 15 to 30 minutes in the catheterization laboratory or an adjacent monitored holding room. The patients were then transferred and monitored in an intensive care unit or a postprocedure telemetry ward. A 12-lead ECG was routinely obtained after the procedure, on the following day, and in the event of any chest pain suggesting ischemia. All patients in the present study left the laboratory with a “successful” procedure and underwent postprocedure creatine kinase (CK) determination under a routine protocol followed at our institution that calls for routine CK determination 6 to 8 hours after the procedure, on the following morning, and in the event of any symptoms suggestive of ischemia. CK-MB determination was performed on all CK values of >100 IU/L. When the CK was elevated, it was measured every 8 hours until it returned to baseline values. Patients were maintained on aspirin, and a calcium channel blocker was administered for at least 48 hours after the procedure.
Management of Abrupt Closure
The operators followed general guidelines based on their interpretation of the videofluoroscopic images. However, abrupt closure was managed at the interventionalist’s discretion without a uniform protocol. After the angiographic demonstration of abrupt closure, additional heparin and intracoronary nitroglycerin usually were administered. Abrupt closure was managed with progressively longer balloon inflations, with or without thrombolytic therapy, until a satisfactory angiographic result was obtained. In general, a normal-size balloon was used initially and a longer duration of inflation was attempted, usually for as long as 5 minutes depending on the severity of angina, blood pressure, and ECG changes. If this was unsuccessful, an oversized balloon (0.5 mm larger than the reference diameter) was used. The perfusion balloon catheter was used in patients who were unable to tolerate prolonged inflations with standard balloons. Eighty-two patients (93%) were treated with repeat balloon angioplasty alone. Intracoronary thrombolytics were given only in the presence of an intraluminal, central filling defect or lucency surrounded by contrast material seen in multiple projections or when embolization of intraluminal material was noted downstream. Six patients (7%) received intracoronary thrombolytics, in addition to repeat dilatation, for the treatment of abrupt closure.
Clinical and Procedural Variables
Clinical information at the time of the initial presentation and data obtained at the time of the procedure and at discharge were recorded prospectively on standard case report forms and entered into the Cleveland Clinic Interventional Registry Database. The diagnostic and procedural cineangiograms were reviewed by an experienced angiographer to code for lesion-related morphological variables (eccentricity, length, diameter, angulation, bifurcation stenosis, calcification, dissection, and thrombus-containing lesions). Angiographic measurements before and after the procedure were performed by use of hand-held calipers in the projection showing the most severe stenosis, with the guiding catheter serving as the reference standard. Angiographic data were also entered prospectively into the registry database.
Clinical follow-up data were obtained by trained interventional registry personnel who made telephone contact calls to the referral patients in this study and by visits of patients followed up at our institution. The patients were contacted on a yearly basis after the procedure and were questioned as to the recurrence of symptoms, cardiac hospitalization (for angina, heart failure, or arrhythmias), repeat revascularization, and myocardial infarction. Follow-up events were analyzed and classified by a physician. The families, physicians, or both of deceased patients were interviewed in an effort to determine the cause of death. Autopsy results were obtained when available. Myocardial infarction was defined as prolonged chest pain with a documented rise in CK to more than twice the upper limit of the laboratory normal with a positive MB fraction or development of new Q waves. Each death was defined as cardiac or noncardiac. Cardiac death included sudden cardiac death (witnessed or death occurring within 1 hour of onset of cardiac symptoms or if the patient was found dead having previously appeared to be in normal health), death from arrhythmias, death from documented myocardial infarction, death from progressive congestive heart failure, death after cardiac surgery, and death from other cardiac causes.
All patients included in the present study had a successful procedure. “Success” was defined as an increase of ≥20% in luminal diameter with a final percent diameter stenosis of <50% and no major complications. Major complications were considered to be CABG, Q-wave myocardial infarction, or death and were defined according to NHLBI definitions.13 “Abrupt vessel closure” was considered to be complete (TIMI grade 0) or partial (TIMI grade I or II) closure after establishment of TIMI grade 3 flow during an initially successful dilatation. “Successful reversal of abrupt vessel closure” was defined as a final percent diameter stenosis of <50%, restoration of normal TIMI grade 3 flow beyond the site of closure without in-hospital death, CABG, or the development of Q-wave myocardial infarction. The angiographic definitions used in this analysis have been used in the evaluation of the results of angioplasty and atherectomy and were published previously.14 15 “Coronary dissection” was defined as the presence of a curvilinear filling defect parallel to the vessel lumen, contrast material outside the vessel lumen persisting after passage of the contrast, or a spiral defect obstructing the vessel lumen. “Thrombus” was defined as intraluminal, central filling defect or lucency surrounded by contrast. “CK-MB product” was defined as the product of CK (in international units per liter) multiplied by the percent MB fraction.
Statistical analysis was performed using a computerized statistical analysis program (SAS Institute Inc). Data are expressed as mean±SD. The two groups were compared using the χ2 or Fisher’s exact test to test differences in categorical variables. Continuous variables were compared by Student’s t test. All clinical, morphological, and procedural variables that were different between the two groups at a value of P≤.10 were included in univariate and multivariate logistic regression analyses to identify the factors associated with transient in-laboratory closure and long-term complications. Survival curves were calculated according to the Kaplan-Meier estimates of survival and compared using Wald χ2 test based on the Cox proportional hazards regression model. Univariate and multivariate analyses of factors affecting the freedom from adverse events were also performed using Wald χ2 test and the Cox proportional hazards (multiple) regression model.16 A significance level of .05 was assumed.
The baseline patient information for the two groups is given in Table 1⇓. A comparison of baseline patient demographics in this series with those reported previously reveals many similar patient characteristics.3 7 8 12 17 18 The majority of the patients were men with unstable angina and multivessel disease. Smoking, hypertension, hypercholesterolemia, and a family history of coronary artery disease were prevalent in this population. The group with transient vessel closure had a higher incidence of recent myocardial infarction (>36 hours but <2 weeks). Notably, multivessel disease and left ventricular dysfunction were equally distributed between the two groups.
Limited morphological characteristics are described in Table 2⇓. The morphological lesion characteristics were similar to those of previously published angioplasty and atherectomy series.3 7 8 12 17 18 Most of the stenoses attempted were eccentric, discrete, and noncalcified. In the group with transient vessel closure (group 2), there was a higher incidence of chronic total occlusions (P=.02), bifurcation lesions (P=.04), and thrombus-associated lesions (P=.07).
DCA and procedures performed on saphenous vein grafts were more frequent in the group with in-laboratory vessel closure (P=.001 and P<.0001, respectively) (Table 3⇓). The percent residual stenosis was also higher in this group (27.1±12.7% versus 18.8±11.8%; P=.001). Postprocedure peak CK was significantly higher in the same group, with 50% of the patients in group 2 having an elevation of CK above the upper limit of normal (>180 IU/L) and 30% having a peak CK more than twice that of control. CK-MB was also significantly higher in the same group (55.3 versus 7.7 IU/L; P=.004).
By definition of the cohort, all patients in the present study had a successful procedure, without in-hospital death, Q-wave myocardial infarction, or CABG. Complications are therefore limited to minor complications, as presented in Table 4⇓. All minor complications were more common in group 2, in which there was a higher incidence of coronary dissections, side-branch compromise, thrombus, coronary embolism, and hypotension requiring vasopressors.
Correlates of Transient In-Laboratory Vessel Closure
The presence of coronary dissection was the most important correlate for transient closure (odds ratio, 7.33; P<.0001) (Table 5⇓). Other important predictors included procedures performed on vein grafts, recent myocardial infarction, bifurcation lesions, DCA, and chronic total occlusions.
Clinical follow-up was available for 4839 of 4863 patients (99.5%). The mean follow-up period was 41±23 months (range, 1 to 104 months). The results of this follow-up are shown in Figs 1⇓ and 2⇓. In terms of absolute events, there was a 0% to 2% cardiac mortality rate in the first year with an 11% to 13% incidence of other major ischemic events (myocardial infarction, 1% to 2%; CABG, 4% to 10%; repeat percutaneous coronary intervention, 3% to 7%). Hospitalization for angina, heart failure, or arrhythmias occurred in 19% to 26% of patients in the first year. During years 2 through 5, these complications occurred at an annual rate of 1% to 1.5% for cardiac mortality, 1% for myocardial infarction, 0.5% to 1% for CABG, and 1.5% to 2% for repeat percutaneous coronary intervention, with all of the events being equally distributed between the two groups. During this period (years 2 through 5), cardiac hospitalization occurred at an annual rate of 4% to 6%. After the fifth year, the annual rate for cardiac mortality was 0% to 0.2%; myocardial infarction, 0% to 1.0%; CABG, 0.5% to 1.0%; and repeat percutaneous revascularization, 1.5% to 2.5%. After the first year, major ischemic events occurred at an annual rate of 3% to 5% in years 2 through 5 and 2% to 4% after the fifth year. Cardiac hospitalization after the fifth year occurred at an annual rate of 2% to 5%. Analysis of our long-term clinical follow-up shows that the highest incidence of adverse events occurred within the first year after the procedure and consisted mainly of repeat revascularization procedures (CABG, 4% versus 10% for group 1 versus group 2; repeat percutaneous interventions, 7% versus 3% for group 1 versus group 2). Cardiac hospitalization occurred in the first year at a rate of 19% for group 1 and 26% for group 2. There were no significant differences between the two groups in the incidence of cardiac or noncardiac death. Myocardial infarction, repeat revascularization, and cardiac hospitalization were also equally distributed between the two groups. Fig 2⇓ shows the event-free survival curves (from death, myocardial infarction, CABG, and repeat percutaneous revascularization) for the two groups. At the end of the follow-up period, 61% of patients in group 1 were free from major ischemic events (death, myocardial infarction, CABG, and repeat percutaneous revascularization) compared with 54% in group 2 (P=.85). At the end of the follow-up period, 14% of the surviving patients in group 1 had CCS class III or NYHA class IV angina compared with 15% in group 2 (P=NS). Class III or IV congestive heart failure was present in 9% of the surviving patients in group 1 compared with 10% in group 2 (P=NS).
Correlates of Long-term Complications
Multivariate analysis using Wald χ2 test and the Cox proportional hazards model showed that transient vessel closure was not associated with adverse long-term outcome (Table 6⇓). There was a significant positive correlation between CK and CK-MB product (r=.689; P<.0001). CK-MB product superseded the absolute CK in the multivariate model as a predictor of long-term outcome, and the models including only CK-MB product were statistically as informative as the models including both CK-MB product and absolute CK. Therefore, in the final model, only the CK-MB product was used to reflect elevation of cardiac enzymes.
For cardiac death, transient vessel closure had no effect on cardiac death at follow-up (P=.30). A postprocedure rise in CK-MB was the most important correlate for cardiac death (P<.0001). A procedure on a vein graft was of borderline significance. For noncardiac death, transient vessel closure was not a predictor of noncardiac death—nor was the rise in postprocedure CK-MB. Procedures performed on vein grafts were associated with the occurrence of myocardial infarction on follow-up. There were two correlates for CABG on follow-up: vein graft and directional atherectomy procedures. There were three important correlates for repeat percutaneous revascularization on follow-up: a directional atherectomy procedure (P=.03), a vein graft procedure (P=.03), and recent myocardial infarction (P=.02). Cardiac hospitalization on follow-up was associated with an increased CK-MB (P=.01), a vein graft procedure (P=.04), and a higher residual stenosis (P=.04). Combining all of the major ischemic complications (death, Q-wave myocardial infarction, CABG, repeat percutaneous coronary interventions), there were four predictors for these complications: CK-MB elevation (P=.0005), a vein graft procedure (P=.002), a directional atherectomy procedure (P=.005), and a higher residual stenosis (P=.03). Transient in-laboratory closure had no significant effect on the incidence of ischemic complications on follow-up (P=.45).
Cardiac Enzymes as an Important Predictor of Long-term Complications
Fig 3⇓ shows the relation between the peak CK-MB value after the procedure and the incidence of cardiac death on follow-up and illustrates the importance of minor elevations of CK-MB in increasing the risk for cardiac death. When the study population was classified according to peak postprocedure CK (a more commonly used measure of cardiac enzyme elevation), there was also a significantly higher incidence of cardiac death in the groups with higher CK (Fig 4⇓). When the CK threshold was set at 180 IU/L (the upper limit of the laboratory normal value), patients with CK of >180 IU/L had an 8% incidence of cardiac death compared with 4% for patients with CK of <180 IU/L (P<.0001). Cardiac death was equally distributed between groups 1 and 2 and occurred in 8.1% of patients with CK of >180 IU/L in group 1, and 6.8% of patients with CK of >180 IU/L in group 2 (P=NS). The results were comparable when the CK threshold was set at 360 or 540 IU/L. Classification of the study population into three groups according to incremental, nonoverlapping CK levels (Table 7⇓) shows that there was a progressive increase in cardiac mortality with increasing CK values, with the group with CK levels of >540 IU/L having the highest mortality rate.
Acute coronary artery closure remains a serious complication of percutaneous coronary interventions, occurring in as many as 10% of procedures. Approximately half of the patients with abrupt closure can be treated with repeat dilatation, whereas the other half are managed with emergency CABG or treated medically.1 3 4 5 8 Although reopening of abrupt closure by angioplasty is sustained in the majority of patients treated with this modality, reocclusion occurs in few patients. Although it is infrequent, abrupt closure has been shown to be associated with increased early mortality and morbidity, with a high incidence of death (as much as 5%), myocardial infarction (as much as 27%), and the need for emergency CABG (as much as 10%).4 Therefore, abrupt occlusion remains the most important risk factor for in-hospital ischemic complications, including mortality, myocardial infarction, and CABG. The NHLBI reported an in-hospital mortality rate of 5% for each of the three treatment groups (repeat dilatation, CABG, or medical treatment) compared with 1% for occlusion-free patients.8 In-hospital infarction rates ranged from 27% in patients treated with dilatation to 56% in the patients managed with surgery compared with 2% in patients without occlusion. Similarly, other studies have reported a 0% to 8% incidence of death, 20% to 54% incidence of myocardial infarction, and 20% to 72% incidence of emergency CABG.1 2 3 4 5 6 7 8 9
There is less information about the long-term effects of abrupt closure. Some studies have shown an excellent long-term outlook for all treatment modalities (redilatation, CABG, or medical treatment).3 4 5 It has been suggested that the 6-month follow-up with successful redilatation is benign and is comparable to the reported 6-month follow-up results of patients after successful PTCA.3 However, these studies involved a small number of patients and have limited follow-up and therefore might have missed a small but significant adverse long-term outcome. On the other hand, the NHLBI investigators provided a detailed analysis of their experience with abrupt closure in 1801 patients recruited for study in 1985 through 1986 and showed that regardless of the management of acute closure (repeat dilatation, CABG, or medical treatment), patients with periprocedural occlusion had a far worse outcome than patients without occlusion, with a higher cumulative 2-year event rate in patients with acute occlusion compared with patients with no procedural acute vessel closure.8 It was not possible, however, to determine whether this worse outcome is related to the acute vessel closure per se or due to other associated variables. Of note, most of the adverse events in that study occurred during the initial hospitalization.
Correlates of Long-term Complications
Our analysis of long-term outcome shows that isolated reversible in-laboratory vessel closure does not have an adverse effect on long-term prognosis (Table 6⇑). An associated rise in cardiac enzymes, however, was clearly shown to be associated with an increase in cardiac death and with a higher overall incidence of major ischemic complications. This is consistent with our previous observation that mild elevation of cardiac enzymes after apparently successful percutaneous interventions has an impact on long-term outcome.11 In that study, a slight increase in peak postprocedure CK to 181 to 360 IU/L was associated with a higher incidence of cardiac death and major ischemic complications compared with a “normal” CK (ie, CK <180 IU/L). The results are also congruent with prior observations from several studies showing that patients with minimally elevated CK-MB levels had a worse prognosis compared with patients with CK-MB of 0 IU/L, suggesting an important prognostic value for small increases in CK-MB.19 20 Fig 3⇑ clearly shows that even minor elevations in CK-MB are associated with increased cardiac mortality on follow-up, further supporting our data.
The present study demonstrates a prognostic significance for minor elevations of CK-MB after percutaneous interventions but does not establish the mechanism(s) by which increased cardiac enzymes affect long-term prognosis. Yet it is important to identify the possible mechanisms that have support in the literature to determine whether any of them are consistent with this observation. It is likely that increased cardiac enzymes reflect small zones of necrosis. These microinfarcts can create zones of slow conduction that increase the susceptibility to ventricular arrhythmias via microreentrant circuits.21 22 23 In addition, ventricular arrhythmias after microembolization may be triggered by a focal mechanism.24 Thus, it is conceivable that microinfarcts associated with minor increases in CK-MB provide a nidus for ventricular arrhythmias via a microreentry or a focal mechanism.21 22 23 24 Another potential mechanism that could increase the likelihood of cardiac death is through the compromise of coronary collaterals. The interruption of collateral blood flow has been shown to potentiate the ischemic effects of subsequent coronary occlusion.22 This can lead to a higher incidence of ventricular arrhythmias and a larger infarct. In other words, the initial event may “sensitize” the heart to the effect of a subsequent ischemic insult.22
Determinants of Abrupt Closure
Several clinical and angiographic features have been associated with an increased risk of abrupt closure during coronary angioplasty. The most comprehensive evaluation of the predictors of acute closure has been provided by Ellis et al,7 who identified seven preprocedural and four procedural risk factors for abrupt closure. These included female sex, multivessel disease, intracoronary thrombus, long lesions, branch-point location, bend point, other stenoses ≥50% in the dilated vessel, coronary dissection, residual stenosis >35%, and a final translesional pressure gradient ≥20 mm Hg. Additional risk factors were identified in other studies and include severe stenosis before angioplasty, lesion eccentricity, lesion calcification, right coronary artery location, high-risk status for CABG, unstable angina, diabetes, inadequate antiplatelet therapy, extreme age, excessive proximal tortuosity, and the modified American College of Cardiology–American Heart Association classification.25
In the present study, coronary dissection was the most important predictor for transient closure, followed by vein graft procedures and bifurcation lesions. Recent myocardial infarction, chronic total occlusions, and DCA also were predictors of abrupt closure. The association of abrupt closure with DCA is interesting and has been confirmed in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT), which reported an abrupt closure rate of 6.9% for DCA versus 2.8% for PTCA (P=.0004).26 The CAVEAT study also reported a higher incidence of CK release after DCA compared with PTCA.18 The reason for this enzyme “leak” is not known. It is possible that DCA is associated with an increased rate of distal embolization resulting from a bulky device compared with smaller PTCA catheters. Waksman et al27 recently reported distal embolization in 22% of DCA procedures performed on native coronaries and in 48% of procedures performed on saphenous vein grafts. DCA has also been associated with a higher incidence of non–Q-wave infarction, abrupt vessel closure, and side-branch occlusion compared with angioplasty.26
Causes of Abrupt Closure
Abrupt closure usually occurs in the setting of coronary dissections, but it can follow the formation of intracoronary thrombus without dissection2 5 8 28 or, rarely, be caused exclusively by spasm.29 We did not attempt to analyze the immediate cause of vessel closure (dissection, thrombus, or spasm) because direct assessment of the mechanism of abrupt closure is limited by the relative imprecision of coronary angiography, which does not provide direct information about the lumen or, more important, the plaque and vessel wall. And although the classic curvilinear or spiral-shaped filling defects are characteristic of dissection, the relatively more common angiographic appearance of contrast staining, radiolucent haziness, or an obstructive filling defect may be seen with either dissection or thrombus. In fact, the angiographic appearance of abrupt closure may be indeterminate in as many as 45% of patients.2 9 Furthermore, closure morphology (thrombus or dissection) does not appear to have a demonstrable correlation with the likelihood of successful outcome or with the effectiveness of the various treatment strategies,2 9 although this is a point of some controversy.5
Transient Abrupt Closure and Increased CK
The present study shows a strong association between transient vessel closure and increased CK-MB. Half of the patients with “successfully” reversed transient closure had an elevated postprocedure CK level above the control level, and 30% had a level more than twice that of control. The CK-MB product was also significantly higher in the group with abrupt closure (55 versus 8 IU/L, P=.004). Similar results have been reported by Lincoff et al,9 who reported that among successfully managed patients with abrupt vessel closure, the incidence of non–Q-wave myocardial infarction, defined as an elevation in peak CK to more than three times the upper limit of normal with positive MB fraction, was 30%. DeFeyter et al3 4 also reported that nonfatal myocardial infarctions occurred in 36% of the patients, with most of these infarctions being relatively small non–Q-wave myocardial infarctions.
It was interesting to note that although the survival curves of the two groups were almost superimposable, when the data were categorized by CK or CK-MB product levels, it became obvious that CK elevation associated with abrupt closure is an important determinant of long-term outcome (Figs 3⇑ and 4⇑). This raises an important concern—that minor complications judged by interventionalists not to be important might affect the outcome of such procedures. Our results raise a flag of caution about the prognostic value of cardiac enzyme elevation after percutaneous procedures, especially with new devices that tend to be associated with the release of CK-MB. We propose that future interventional studies take a closer look at the relation of CK-MB or other cardiac biochemical markers to long-term prognosis.
The present study was a retrospective evaluation of the long-term outcome of successfully treated vessel closure. Therefore, there was no rigid, prospectively designed protocol to manage this complication, although in most patients, the initial step was the use of intracoronary nitroglycerin followed by redilatation of the occluded segment, as described in “Methods.” Moreover, patients treated with salvage atherectomy or intracoronary stenting were not included in the study. Although the exclusion of these alternative treatment strategies, which are available for the management of vessel closure, limits the conclusions of the present study, it does not necessarily weaken the conclusions, since the main point of the study was not to compare different treatment modalities for the management of abrupt closure (which requires large, prospectively randomized trials) but rather to study the effect of successfully treated abrupt closure on long-term outcome, regardless of the approach used to successfully treat such occlusions. Furthermore, we believe that the aggressive anticoagulation regimen necessitated by stenting, especially for abrupt closure, might have an impact on the outcome of these patients. Because of the retrospective nature of this analysis, the time to CK peak cannot be determined with certainty, and we cannot exclude a potential source of bias related to the possibility that patients with transient closure might have been treated differently, with different frequency and intervals of sampling of cardiac enzymes, than were routine patients. Another limitation of the present study is that objective measurements of anticoagulation were not made with in-laboratory activated clotting times. The study spanned a period of time when in-laboratory measurements of activated clotting times were not available, and because of the retrospective nature of the study, a rigid anticoagulation protocol was not followed.
Transient in-laboratory closure per se has no effect on the incidence of long-term ischemic complications (death, myocardial infarction, CABG, or repeat dilatation). However, a rise in postprocedure cardiac enzymes was the most important correlate of cardiac death and the overall frequency of major ischemic complications on follow-up. This confirms our previous findings that elevation of postprocedure CK has an important effect on long-term prognosis. We recommend routine cardiac enzyme measurements after coronary procedures and believe that it is particularly imperative to obtain periprocedural cardiac enzyme determination in all patients with in-laboratory vessel closure.
We gratefully acknowledge Gan Howell, Deborah Lynch, Freddie Ford, J. Patrick Lang, and all of the staff of the Interventional Registry at The Cleveland Clinic Foundation for their effort in the collection of data.
- Received November 11, 1994.
- Revision received December 5, 1994.
- Accepted December 18, 1994.
- Copyright © 1995 by American Heart Association
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