CORRESPONDENCE: RESEARCH CORRESPONDENCE
Prodromal Angina Limits Infarct Size in the Setting of Acute Anterior Myocardial Infarction Treated With Primary Percutaneous Intervention
Filippo Ottani, MD*,
Mario Galli, MD,
Santino Zerboni, MD and
Marcello Galvani, MD
* Fondazione Cardiologica "M.Z. Sacco", P.zza F.lli Ruffini, 6, 47100 Forlì, Italy (Email: ottanif{at}omf.dsnet.it).
To the Editor:
We demonstrated that prodromal angina reduces infarct size in the setting of acute myocardial infarction (MI) treated with fibrinolysis (1), and this favorably influences outcome (2). Although the mechanism(s) remain unclear, we proposed a role for ischemic preconditioning (1), while others suggested accelerated thrombolysis (3). If preconditioning plays a role, the effect should be detectable regardless of how the infarct-related artery (IRA) reperfusion is achieved, and studying patients undergoing primary percutaneous intervention (pPCI) may elucidate such role in determining myocardial protection.
Between January and August 1998, 22 patients were prospectively and consecutively enrolled if they had: 1) chest pain duration  6 h; 2) ST-segment elevation of  1 mm in two contiguous leads; 3) IRA Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 to 1 at baseline angiography and achievement of TIMI flow grade 3; 4) first acute anterior MI; and 5) new-onset prodromal angina within the previous 24 h. Exclusion criteria were hemodynamic instability or the presence of malignant arrhythmias. Symptom status before MI was checked with a questionnaire filled in by the admitting physician. A 12-lead electrocardiogram (ECG) was recorded before and 30 min after angioplasty, then daily until discharge. The sum of ST-segment elevation ( ST ) was measured manually 20 ms after the end of QRS complex. Infarct size was estimated from the 12-lead ECG according to a 32-point QRS system score (4). On the admission ECG, all leads exhibiting 100-µV ST received the maximum QRS score. The sum (QRS0) represented the extent of the area at risk, while that at seven days (QRS7) represented the actual MI size. The "ECG salvage index" was calculated as (QRS0 – QRS7)/QRS0. Blood samples for measuring creatine kinase (CK)-MB levels were taken on admission, and every 8 h for the first 24 h. The infarct size was estimated on the basis of the area under the curve of the CK-MB concentration plotted against time. Left ventriculography (30° right anterior oblique) was taken on baseline, before any revascularization therapy, and six months later. Ventricular volumes and ejection fraction were calculated by the area-length method, and regional wall motion analysis was performed with the centerline method (5). The area-at-risk was defined as the number of chords showing 2 standard deviations below the normal at the baseline, while infarct size as the number of chords with the same feature at the six-month ventriculography. The "ventriculographic salvage index" was defined as (area at risk – infarct size)/area at risk. The primary end point was the reduction of ventriculographic infarct size in patients with prodromal angina. Based on previous experience (2), to detect a 25% relative reduction of infarct size, 11 patients per group were necessary (alpha = 0.05, beta = 0.2). The data are presented as mean values ± standard deviation, if not otherwise stated. Continuous variables were analyzed with an unpaired t test and Mann-Whitney test. A value p 5% was considered significant.
Twenty-two patients were studied; 12 (54.5%) with and 10 (45.5%) without prodromal angina. The clinical and angiographic variables are listed in Table 1. There were no differences between groups. Despite a similar QRS0 (14.6 ± 2.2 vs. 13.4 ± 2.3, p = 0.25), patients with prodromal angina had a smaller infarct size (QRS7: 4.5 ± 2.5 vs. 6.5 ± 2.4, p = 0.07), and a significantly better salvage index (68 ± 21% vs. 52 ± 14%, p = 0.05). The average reduction of ST was similar (63 ± 22% vs. 66 ± 18%; p = 0.67). The area under the CKMB curve was smaller in the prodromal angina group (3,557 ± 2,541 vs. 6,005 ± 2,965 U·l–1·24 h, p = 0.05). Due to very short time-to-treatment, both groups improved ventriculographic parameters at follow-up, but patients with prodromal angina showed an additional 32% of myocardium at risk salvaged (95% confidence interval [CI]: 9% to 56%; p < 0.01), and six-month ejection fraction significantly improved (8%, 95% CI: 0.6% to 15%; p = 0.036). Details are reported in Table 2.
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Table 1. Clinical Characteristics, Angiographic Data, and Ischemia Time According to the Presence of Prodromal Angina
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In this prospective study, the presence of prodromal angina before an anterior MI successfully reperfused with pPCI protects the ischemic myocardium, being associated with a smaller infarct size. Lytic agents take 45 to 60 min to reestablish blood flow; Andreotti et al. (3) reported in patients with MI preceded by prodromal angina that fibrinolysis accelerates IRA reperfusion by 21 min causing smaller infarct size. Angioplasty is not affected by a slow onset of action, and the presence of prodromal angina would not be expected to affect the rapidity of reperfusion. We, therefore, studied the protection afforded by prodromal angina on jeopardized myocytes independent of the earlier dissolution of the thrombus. Because both groups showed myocardial reperfusion, as assessed by the concomitant presence of TIMI flow grade 3 and significant reduction of ST, and no other major baseline clinical and angiographic differences were detected, our data suggest that infarct size reduction is mainly driven by preconditioning, when total occlusion time and reperfusion adequacy are controlled for. However, prodromal angina patients achieved TIMI flow grade 3 slightly earlier, suggesting that its presence might have caused a more unstable clot structure, due to less activated platelets, as supported by experimental data (6).
Although prospective, our study reports a single-center experience in a small and highly selected patient cohort with a remarkably low-risk profile and a very short time-to-treatment. There is a conflicting evidence about the prognostic significance of prodromal angina associated with pPCI, because someone found a better outcome (7), while others not (8,9). We documented that the additional infarct size reduction associated with prodromal angina translated into better long-term ejection fraction, which could positively affect prognosis in an appropriately sized patient cohort. Differences in patient selection and study protocols (retrospective vs. prospective), as well as inconsistency of the prodromal angina definition, could also explain conflicting results.
In conclusion, in our study, prodromal angina leads to a smaller infarct size most likely through ischemic preconditioning. This might represent a clinical "marker" of myocardial viability. Larger prospective trials are needed to demonstrate whether this observation translates into a better outcome in patients receiving pPCI.
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References
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- Ottani F, Galvani M, Ferrini D, et al. Prodromal angina limits infarct size. A role for ischemic preconditioning Circulation 1995;91:291-297.[Abstract/Free Full Text]
- Kloner RA, Shook T, Antman EM, et al. Prospective temporal analysis of the onset of preinfarction angina versus outcomean ancillary study in TIMI-9B. Circulation 1998;97:1042-1045.[Abstract/Free Full Text]
- Andreotti F, Pasceri V, Hackett DR, Davies GJ, Haider AW, Maseri A. Preinfarction angina as a predictor of more rapid coronary thrombolysis in patients with acute myocardial infarction N Engl J Med 1996;334:7-12.[Abstract/Free Full Text]
- Selvester RH, Wagner GS, Hindman NB. The Selvester QRS scoring system for estimating myocardial infarct size Arch Intern Med 1985;145:1877-1881.[CrossRef][ISI][Medline]
- Sheehan FH, Bolson EL, Dodge HT, Mathey DG, Schofer J, Woo HW. Advantages and application of the centerline method for characterizing regional ventricular function Circulation 1986;74:293-305.[Abstract/Free Full Text]
- Hata K, Whittaker P, Kloner RA, Przyklenk K. Brief antecedent ischemia attenuates platelet-mediated thrombosis in damaged and stenotic canine coronary arteriesrole of adenosine. Circulation 1998;97:692-702.[Abstract/Free Full Text]
- Ishihara M, Inoue I, Kawagoe T, et al. Effect of prodromal angina pectoris on altering the relation between time to reperfusion and outcomes after a first anterior wall acute myocardial infarction Am J Cardiol 2003;91:128-132.[CrossRef][Medline]
- Zahn R, Schiele R, Schneider S, et al. Effect of preinfarction angina pectoris on outcome in patients with acute myocardial infarction treated with primary angioplasty (results from the Myocardial Infarction registry Am J Cardiol 2001;87:1-6.[ISI][Medline]
- Tomoda H, Aoki N. Comparison of protective effects of preinfarction angina pectoris in acute myocardial infarction treated by thrombolysis versus by primary coronary angioplasty with stenting Am J Cardiol 1999;84:621-625.[CrossRef][ISI][Medline]
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References