Study objective: To evaluate the incidence and clinical factors related to the persistence of infarct-associated pericardial effusion (PE) after primary angioplasty.
Design: Consecutive case-series analysis.
Setting: Coronary care unit in a university hospital.
Patients: Three hundred ninety-one consecutive patients with acute myocardial infarction (AMI) who underwent successful primary percutaneous transluminal coronary angioplasty (PTCA) at hospital admission.
Interventions: Coronary angiography and primary PTCA on hospital admission and serial echocardiography.
Measurements and results: The status of coronary flow before and after primary PTCA was evaluated by coronary angiography at hospital admission, while PE was studied by echocardiography within 24 h of admission and 1 month after the onset of AMI. PE was present in the acute phase in 76 patients (19%), and patients with PE had a significantly higher incidence of in-hospital death than those without PE (11% vs 2%, p < 0.001). Among 68 patients who had PE in the acute phase and underwent echocardiography 1 month later, PE persisted to 1 month after the onset of AMI (persistent PE) in 26 patients (38%). Patients with persistent PE had a significantly higher incidence of pericardial rub (p = 0.010), Killip class > 1 (p = 0.025), no reflow after PTCA (p = 0.026), lower incidence of collaterals (p = 0.024), and tended to have higher peak creatine kinase (CK) [p = 0.05] levels than those with transient PE. When five variables (peak CK, collaterals, no reflow, pericardial rub, and Killip class > 1) were used in the multivariate analysis, pericardial rub (p = 0.023; odds ratio [OR], 5.45), absence of collaterals (p = 0.011; OR, 0.16), and Killip class > 1 (p = 0.027; OR, 3.80) were the significant variables related to persistent PE.
Conclusions: PE remains a relatively common complication of AMI even in the era of reperfusion therapy and is associated with increased mortality. Furthermore, the presence of a pericardial rub, Killip class > 1, and absence of collateral flow in the early phase of the infarct are associated with persistence of the PE to 1 month meter the onset of AMI.
Key words: angioplasty; myocardial infarction; pericardial effusion
Abbreviations: AMI = acute myocardial infarction; CK = creatine kinase; OR = odds ratio; PE = pericardial effusion; PTCA = percutaneous transluminal coronary angioplasty
Pericardial effusion (PE) is a relatively common complication during the course of acute myocardial infarction (AMI). (1-5) Prior to the introduction of reperfusion therapy, Galve et al (6) reported that reabsorption of PE in the acute phase of the infarct was slow and PE could persist for weeks to months after the infarct. Although early reperfusion therapy has reduced the mortality rate in patients with AMI, coronary flow to the infarct zone before, as well as after, primary percutaneous transluminal coronary angioplasty (PTCA) is an important determinant of final infarct size and in-hospital complications, including PE in the acute phase. (5,7-11) An echocardiogram demonstrating PE may indicate fluid retention, but it is not diagnostic of pericarditis since pericardial fluid may also accumulate as a result of increased hydrostatic pressure. A pericardial rub is the most specific clinical sign of pericarditis, but the clinical course of PE with and without a pericardial rub after primary PTCA has not been determined. In this report, we evaluated pericardial rub along with angiographic and other clinical factors to determine the important factors related to the course of PE after successful primary PTCA.
MATERIALS AND METHODS
We studied 391 consecutive patients admitted to the coronary care unit with their first ST-segment elevation AMI (April 1, 1988, to March 31, 2000) who underwent successful primary PTCA (< 50% diameter stenosis of the infarct-related artery after primary PTCA) within 12 h of the onset and adequate echocardiographic imaging quality. All the patients who survived to the chronic phase (377 patients) underwent follow-up coronary angiography (1 month after the onset of AMI) with a patent culprit lesion (< 75% diameter stenosis). Patients with reinfarction or repeat PTCA were not included in this study.
The diagnosis of AMI was based on chest pain lasting > 30 min, persistent ST-segment elevation > 0.1 mV in two or more contiguous leads, and increase in the serum creatine kinase (CK) levels with > 5% MB fraction. Measurement of CK was carried out every 8 h through the first 2 days after hospital admission, and the peak value was used in this study. Each patient was monitored continuously in the coronary care unit. Major arrhythmias included transient atrial fibrillation and third-degree atrioventricular block requiring temporary pacing during the first 3 days after the hospital admission. Physical examinations were performed at hospital admission, and Killip class was used to determine the state of congestive heart failure. Care fir auscultation was performed at least twice daily, and pericardial rub was considered to be a scratchy, grating, or creaking noise heard in systole, middiastole, and presystole or in any one of these phases. Identification of pericardial rub was based on nonconformity with the characteristic locations, radiations, respiratory responses of most murmurs, and thrills. Auscultatory, palpatory, and respiratory observations were performed independently within a few minutes of each other, and the diagnosis of pericardial rub was made only after agreement by more than two cardiologists. The detection of pericardial rub within 24 h after primary PTCA was recorded.
A clinical history of hypertension, diabetes mellitus, hypercholesterolemia, and smoking was determined from patient interview or medical records. Blood samples were obtained to measure serum total protein and albumin within 2 days of the follow-up echocardiography. Informed consent was obtained from each patient before cardiac catheterization, and the investigational protocol was approved by the institutional review board of the Kansai Medical University Hospital.
All patients were administered aspirin (81 mg) and 3,000 U of IV heparin just after the diagnosis of AMI. After written informed consent was obtained, the patients were taken to the cardiac catheterization laboratory as soon as possible to undergo an emergency coronary angiogram. After arterial cannulation, all patients received heparin (7,000 IU) and isosorbide dinitrate (2 mg), and baseline angiography was performed. PTCA was attempted whenever there was occlusion or subtotal occlusion of the infarct-related artery with use of an exchangeable guidewire system. Successful PTCA was defined as a percentage diameter stenosis of the infarct-related artery < 50% after reflow. The culprit lesion was successfully dilated in all patients. After catheterization, patients were admitted to the coronary care unit for intensive monitoring. An IV infusion of heparin was maintained for 3 to 5 days, with the dose adjusted to achieve a therapeutic level of anticoagulation. Coronary flow of the infarct-related artery before PTCA was graded visually according to the Thrombolysis in Myocardial Infarction study classification: grade 0 flow as total occlusion. Collateral channels were graded from the initial angiography, and a patient was considered to have collaterals to the infarct zone if the collateral perfusion grade was 2 or 3 described by Rentrop et al. (12) Angiographic no-reflow phenomenon following primary PTCA was defined as Thrombolysis in Myocardial Infarction grade < 3 flow in the presence of a widely patent epicardial coronary artery, despite the absence of dissection, thrombus, or distal vessel cut-off suggestive of macroembolization. Angiograms were analyzed by three experienced angiographers without knowledge of the clinical data.
Two-dimensional and M-mode echocardiography were performed within 24 h after hospital admission (acute phase) with an echocardiography system (Sonos 2500, 5500; Agilent Technologies; Palo Alto, CA), and all classic views were recorded on videotape for subsequent analysis. Analysis of the left ventricular wall was performed in 16 segments, (13) and the number of segments with advanced asynergy (akinesis or dyskinesis) was calculated. The presence of PE was assessed by the method described by Horowitz et al. (14) An epicardial/pericardial separation that persisted throughout the cardiac cycle (D pattern) was considered diagnostic of PE. Left ventricular wall motion and PE were determined by two independent observers who had no knowledge of the clinical and angiographic data. In eases of disagreement, consensus was established with a third observer.
In all patients who survived to the chronic phase, coronary angiography was repeated to confirm the patency of infarct-related artery, and echocardiography was performed to assess left ventricular wall motion and the presence of PE (25 to 32 days after the onset of AMI). The patients with PE in acute and chronic phases were considered to have persistent PE. Angiograms and echocardiograms in acute and chronic phases were analyzed by the same observers.
Results are reported as the mean [+ or -] SD. Statistical analysis between the two groups was performed using Student t test for continuous variables and Fisher Exact Probability Test for discrete variables. All calculated p values were two tailed. Stepwise logistic regression analysis was performed to evaluate the important variables related to persistent PE. A p value < 0.05 was considered significant.
Seventy-six of 391 patients (19%) had PE in the acute phase of AMI. Patients with PE in the acute phase had a significantly larger number of advanced asynergic segments, higher peak CK, and higher incidence of Killip class > 1, pericardial rub, and angiographic no reflow than those without PE (Table 1). Fourteen patients died in the hospital. There was a significantly higher incidence of in-hospital death in patients with PE (six patients died of heart failure, and two patients died of cardiac rupture) compared to those without PE (four patients died of heart failure, and two patients died of cardiac rupture).
Clinical Course of PE
Among 76 patients with PE in the acute phase, echocardiography was performed at 1 month after the onset of AMI in 68 patients (8 patients died in the acute phase). PE was detected in 26 patients (38%) in the chronic phase (persistent PE), while PE was absent (transient PE) in 42 patients. None of the 68 patients had echocardiographic or clinical symptoms of cardiac tamponade, or required an alteration of therapy. The patients with persistent PE had a significantly higher incidence of pericardial rub and Killip class > 1, and tended to have higher peak CK and a larger number of advanced asynergic segments at hospital admission than those with transient PE (Table 2). The patients with persistent PE had a significantly larger number of advanced asynergic segments in the chronic phase than those with transient PE. There were no significant differences in total protein (7.0 [+ or -] 0.8 g/dL vs 7.1 [+ or -] 0.7 g/dL [[+ or -] SD], p = 0.598) and albumin (3.7 [+ or -] 0.8 g/dL vs 3.9 [+ or -] 0.8 g/dL, p = 0.332) in the chronic phase between the two groups.
There were no significant differences in elapsed time from the onset of symptoms to primary PTCA, and the incidence of total occlusion of the culprit lesion before primary PTCA, multivessel disease, and left anterior descending lesion between the two groups. However, the patients with persistent PE had a significantly lower incidence of collaterals and a higher incidence of no reflow than those with transient PE (Table 3). To determine the important variables present in the acute phase of the infarct that may be related to the subsequent development of persistent PE, five variables (peak CK, collaterals, no reflow, pericardial rub, and Killip class > 1) were used in the multivariate analysis. From this analysis, pericardial rub (regression coefficient = 1.695; p = 0.023; odds ratio [OR], 5.45), collaterals (regression coefficient = - 1.830; p = 0.011; OR, 0.16), and Killip class > 1 (regression coefficient = - 1.334; p = 0.027; OR, 3.80) emerged as the significant variables related to the subsequent development of persistent PE.
Pericardial Rub Associated With PE
Among 68 patients with PE in the acute phase who survived to the chronic phase, pericardial rub was detected in 14 patients and was absent in 54 patients (Table 2). Ten of 14 patients (71%) with PE and a pericardial rub had persistent PE, while 16 of 54 patients (30%) with PE but no pericardial rub had persistent PE; the difference was significant (p = 0.010). The patients with PE and a pericardial rub had a significantly higher incidence of major arrhythmias (atrial fibrillation, six patients; third-degree atrioventricular block, two patients) compared to those with PE but no pericardial rub (atrial fibrillation, eight patients; third-degree atrioventricular block, five patients) [p = 0.039].
Before the reperfusion era, the prevalence of PE in patients with AMI was reported to be 21% at day 10 and 11% at 3 months after the onset of AMI. (6) In our study, despite successful primary PTCA, the incidence of PE in the acute phase was 19%, and patients with PE in the acute phase had a significantly larger number of advanced asynergic segments, higher peak CK, and a higher incidence of Killip class > 1, pericardial rub, and no reflow than those without PE. Myocardial lymph drains to the epicardial surface of the heart, to the pericardial space, and ultimately to the mediastinum and right-heart cavities. (15) Thus, accumulation of pericardial fluid may result from increased production of myocardial interstitial fluid and/or from slower absorption due to elevated central venous pressure. In AMI, the occurrence of PE can be due to pericardial irritation (infarct pericarditis) or to increased hydrostatic pressure with fluid retention (hydropericardium). (1,4,16) Considering the fact that Killip class still remains a useful indicator of left ventricular dysfunction and early mortality in patients with reperfusion therapy, (17) our data are consistent with the previous report (5) that heart failure due to larger infarct size and pericardial irritation are the important factors associated with the occurrence of PE in the acute phase of AMI after successful primary PTCA.
PE in the acute phase persisted to 1 month after the onset of AMI in 38% of our patients; pericardial rub, along with Killip class > 1 and the absence of collaterals, were found to be independent factors related to the subsequent development of persistent PE. Infarct pericarditis occurs with anatomically transmural infarction and is localized to the infaret zone. A pericardial rub is a most specific noninvasive sign of pericardial inflammation, and pericardial rub is reported to be the most frequent clinical sign during infarct pericarditis. (1,4) In our previous report, (18) we found that pericardial rub was a reliable sign of extensive myocardial damage after primary PTCA. Therefore, a possible mechanism contributing to the close relation between pericardial rub and persistent PE was a higher incidence of anatomically transmural infarction in patients with a pericardial rub.
Atrial fibrillation and third-degree atrioventricular block in AMI occur more frequently in patients with larger infarct size and depressed left ventricular function. (19-21) Dubois et al (22) reported that the patients with a pericardial rub in the acute phase of AMI had a higher incidence of congestive heart failure or major arrhythmias (atrial fibrillation, second- or third-degree atrioventricular block). Consistent with these prior observations, we also found a higher incidence of atrial fibrillation and/or third-degree atrioventricular block when a pericardial rub was present in patients with a PE.
Angiographic studies (9,23) have indicated that approximately two thirds of patients with AMI have a totally occluded infarct-related coronary artery before reperfusion therapy. Clements et al (9) also reported that antegrade flow of the infarct-related artery before angioplasty and collateral flow to the infarct zone were significant determinants of final infarct size after successful angioplasty. In our study, we found that while there were no significant differences between the two groups in the elapsed time from the onset of AMI to primary PTCA and the incidence of total occlusion of the infarct-related artery before PTCA, the patients with persistent PE had a lower incidence of collaterals before PTCA than those with transient PE. Moreover, a significantly larger number of left ventricular segments with advanced asynergy was observed in the chronic phase in patients with persistent PE compared to those with transient PE. Thus, the absence of collateral flow to the infarct zone before primary PTCA may have blunted the salvage of jeopardized myocardium, which lead to a larger infarct size in the chronic phase in patients with persistent PE.
Although conducted in consecutive patients, this was a retrospective analysis of prospectively accumulated data in patients with successful primary PTCA. Further studies are needed to confirm our data in a larger group of patients with AMI. However, prompt assessment of coronary perfusion and detection of pericardial rub may aid in making decisions concerning the use of drugs to improve microvascular function and left ventricular function after primary PTCA.
PE remains a relatively common complication of AMI even in the era of reperfusion therapy, and the presence of a pericardial rub, Killip class > 1, and absence of collateral flow in the early phase of the infarct are associated with persistence of the PE to 1 month after the onset of AMI.
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Manuscript received April 20, 2004; revision accepted March 16, 2005.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml).
Correspondence to: Tetsuro Sugiura MD, FCCP, Department of Laboratory Medicine, Kochi Medical School, Kohasu Oko-cho Nankoku City, Kochi, Japan 783-8505; firstname.lastname@example.org
* From the Department of Laboratory Medicine (Drs. Sugiura, Kudo, Okumiya, and Yamasaki), Kochi Medical School, Koehi; and Cardiovascular Center (Drs. Nakamura and Iwasaka), Kansai Medical University, Osaka, Japan.
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