Long-Term Cardiac Function and Outcome in Patients Receiving Primary Angioplasty for Acute Myocardial Infarction at a Community

After demonstrating that thrombotic coronary artery occlusion is the major proximate cause of myocardial infarction (MI), research efforts focused on how to provide the most effective reperfusion therapy to the largest number of patients.1 The GISSI and GUSTO trials showed that treatment with thrombolytic agents decreased mortality by 3%.2,3 However, primary angioplasty has been shown to be more effective at reestablishing coronary blood flow and is associated with better 30-day mortality as compared with thrombolytic therapy.4–6 In addition, Zijlstra et al. showed that patients in a tertiary care referral center who were initially treated with primary angioplasty had better long-term rates of reinfarction, and lower mortality when compared to patients treated with thrombolytic therapy.7 These findings were recently confirmed in community hospitals by the C-PORT trial.8 In the United States, approximately 500,000 patients per year present to hospitals and meet criteria for reperfusion therapy.9 However, 80% of these patients present to community hospitals and thus do not have access to primary angioplasty. Studies performed at high-volume community angioplasty centers clearly show the short-term benefits of primary angioplasty when compared to thrombolytic therapy.10–18 We compared the long-term effects of primary angioplasty versus thrombolytic therapy on cardiac function for patients who experienced acute MI and presented to community hospitals. Methods The study patients were admitted between January 1990 and January 1994 to Sentara Leigh Hospital, a 250-bed community hospital without in-house cardiac surgical facilities. All patients with suspected MI who were brought to the cardiac catheterization laboratory with the intention of undergoing emergency PTCA were enrolled in this study. A cohort of patients contemporaneously treated with thrombolytic therapy was identified by review of the emergency department logbook. At the time of initial treatment, primary angioplasty was not uniformly used as a treatment for acute MI, and the decision to use primary angioplasty versus thrombolytic therapy was at the discretion of the treating physician. The cohort treated with thrombolytic therapy was matched with the primary angioplasty group on the following variables: age, location of infarction, and gender as well as approximate duration of symptoms prior to presentation to the emergency department. The matched control group was formed without any knowledge of the patients’ subsequent clinical outcomes. Comorbid conditions were similar between the two groups (Table 1). Data from the initial 122 hospitalized patients are also presented in Table 1 (n = 61 patients in each group). Patients who died during the initial hospitalization were included in the cumulative death count for each group, but were obviously excluded from the long-term follow-up for cardiac function. All patients met the following criteria for acute MI: 1) ST elevation in two contiguous electrocardiographic leads consistent with myocardial injury; and 2) typical angina or other symptoms suggestive of an evolving acute MI. For the purpose of matching the two groups, MI was defined electrocardiographically as anterior if ST elevation was in leads V1 through V6, inferior if ST elevation was in leads II, III or aVF and lateral if ST elevation was in leads I and aVL. Patients presenting in cardiogenic shock or requiring rescue angioplasty were excluded from these groups since primary angioplasty is a defined treatment in these patient populations. Short-term results and further description of these patient groups has been previously reported.15 All patients undergoing primary angioplasty were evaluated and treated by one of eight interventional cardiologists who work at both the community hospital and the tertiary care referral center. The research protocol was submitted and approved by the institutional review board and all data gathered were governed by institutional regulation. Information was gathered by chart review in private office, hospital, and healthcare databases and mortality verification was provided by the Social Security Death Index. All diagnostic studies, including cardiac catheterization, radionuclide radiography and echocardiography, were interpreted by physicians who had no knowledge that the patient was included in a clinical study. Information collected included records regarding recurrent MI or readmission for cardiac diagnoses, repeat angiography, echocardiography, radionuclide radiography, medications and date of death if applicable. Cause of death was ascertained by chart review and death certificates; date of death was recorded. The primary endpoint of this long-term study was ejection fraction, which was measured by echocardiogram, cardiac catheterization or radionuclide radiography. Because the clinicians were blinded to patient participation in the study, ejection fractions were obtained in the normal course of evaluation and clinical treatment of patients throughout the follow-up period, and not at predetermined intervals. These data were collected until August 31, 2000. Secondary endpoints included major adverse cardiac events (MACE), defined as reinfarction, revascularization >= 6 months after initial presentation or cardiac death. Statistical analysis was performed using unpaired two-tailed t-tests for continuous variables and Chi-squared analysis for discrete variables. Results Sixty-two patients were originally enrolled in each of the primary angioplasty and thrombolytic therapy groups. The in-hospital outcomes for these patients were previously reported.15 The patient groups were matched for age, MI location and gender. History of prior MI, PTCA or bypass grafting was more common in the patients treated with primary angioplasty (Table 1). One patient underwent both therapies at different times during the treatment period and was included in each arm for the short-term follow-up. Since this study sought to examine long-term treatment effects on ejection fraction, this patient was eliminated from both groups to avoid potential bias. The average ejection fraction was statistically higher for the primary angioplasty group compared to the thrombolytic therapy group (51.4% versus 45.8%, respectively; p =0.038). Given the small sample size, as expected, the total number of patients experiencing MACE was not statistically significant between the two groups (p = 1.0). In addition, as shown in Table 2, when MACE are analyzed individually, the two groups show no statistically significant difference for revascularization (p = 0.90), recurrent MI (p = 0.75) or cardiac death (p = 0.75). In addition, the time to onset of a MACE and the time free from MACE were not statistically different between the two groups (p = 0.85 and p = 0.25, respectively). Of the 61 patients receiving thrombolytic therapy, three deaths occurred on the first admission, one from hemorrhagic cerebrovascular accident, one from thromboembolic cerebrovascular accident and one from unknown cause. In the remaining patients, the average length of follow-up was 47 months. Ejection fraction was available on 52 patients; thus, an analysis of cardiac function could be performed on 90% of those surviving initial hospitalization. Sixteen patients suffered MACE, with 4 of the 16 experiencing recurrent MI. Seven deaths occurred during the follow-up period (2 from cardiac causes). Of the 61 patients receiving primary angioplasty, two deaths occurred on the first admission, one from a perforated duodenal ulcer and one from a nonhemorrhagic cerebrovascular accident occurring 2 days after the angioplasty procedure. In the remaining patients, the average length of follow-up was 57 months. Ejection fractions were available on 54 patients; thus, an analysis of cardiac function could be performed on 92% of those surviving initial hospitalization. Sixteen deaths occurred after the initial treatment (four from cardiac cause). Sixteen patients suffered MACE, with 4 of the 16 experiencing recurrent MI. Evaluation of patient demographics on enrollment in this study reveals a higher proportion of prior cardiac events in the patients undergoing primary angioplasty for MI. This suggests that the ejection fractions prior to treatment may have been lower in the primary angioplasty group. Despite this, ejection fraction was higher at follow-up in the primary angioplasty group, suggesting that the observed difference in ejection fraction between the two groups may have been an underestimate of the real treatment effects of primary angioplasty. Discussion This study shows that primary angioplasty, when performed by experienced operators in a community hospital without surgical back-up, yields long-term improvement in cardiac function as measured by ejection fraction. These results are similar to those reported by Zijlstra et al., who examined outcomes from a center with surgical back-up; our study shows that the results obtained in the larger tertiary care hospital can translate to a smaller community hospital without surgical back-up.7 C-PORT and DANAMI-2, recent studies of primary percutaneous intervention (PCI) performed in community hospitals, showed that treatment with primary angioplasty is associated with improved clinical outcomes as compared with thrombolytic therapy.8,19 The C-PORT trial compared PCI with thrombolytic therapy and found that 6-month rates of death, recurrent MI and stroke were lower in patients treated with PCI. The DANAMI-2 trial examined 30-day rates of death, recurrent MI and disabling stroke in patients treated with thrombolytic therapy in community hospitals versus those transferred to a tertiary referral center for primary angioplasty. Results of the DANAMI-2 trial found that recurrent MI was significantly less in patients transferred to the tertiary care facility for primary angioplasty. These studies, however, did not evaluate cardiac function. In addition, the follow-up period in these two recent studies is shorter than the present study, which adds to the results from multicenter trials without surgical back-up, and shows long-term improvement in cardiac function in patients treated with primary angioplasty. This preservation of cardiac function may help explain the findings of these recent studies showing that primary angioplasty is associated with improved outcome as assessed by all-cause mortality, recurrent MI and stroke. Key predictors of acute MI survival include time to reperfusion and TIMI grade of coronary blood flow with reperfusion.3 Advantages of thrombolytic therapy include ease of administration and shorter time to treatment; however, coronary artery patency rates and short- and long-term outcomes are worse than with primary angioplasty. In addition, as many as two-thirds of patients may have contraindications to thrombolysis.20–22 Primary angioplasty has been shown to have benefits over thrombolytic therapy, but requires a cardiac catheterization laboratory, experienced staff and an interventional cardiologist.4,5 In order to provide primary angioplasty to the majority of patients suffering from acute MI, all patients must either be transferred to tertiary care centers in a timely manner or be provided with primary angioplasty in community hospitals that have angiography suites. To address transfer to tertiary care centers, Zahn et al. compared referred patients to those receiving primary angioplasty on-site and found higher rates of post-infarct angina, revascularization and advanced heart failure in referred patients.23 In addition, they also found that

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