American Journal of Cardiology
Volume 103, Issue 9 , Pages 1183-1188, 1 May 2009

Severity of Coronary Arterial Stenoses Responsible for Acute Coronary Syndromes

Cardiovascular Center Aalst, OLV Clinic, Aalst, Belgium

Received 1 November 2008; received in revised form 21 December 2008; accepted 21 December 2008. published online 16 March 2009.

Article Outline

Acute myocardial infarctions were generally believed to result from plaque rupture and thrombosis at the site of a “mild to moderate” coronary stenosis. To assess the severity of coronary stenoses that predisposed to acute coronary syndrome, the 317 patients prospectively included were (1) 102 patients with acute ST-elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI), (2) 135 patients with non-STEMI or unstable angina pectoris (UAP) referred for semiurgent PCI, and (3) 80 patients with stable angina pectoris (SAP) admitted for elective PCI. Patients with STEMI were included if thrombus aspiration could restore normal antegrade coronary blood flow. After aspiration (but before PCI), a high-quality angiogram was obtained and the reference diameter, minimal luminal diameter, and percentage of diameter stenosis of the culprit lesion were quantified. In patients with non-STEMI/UAP and SAP, aspiration was not performed. Average diameter of stenosis was similar in patients with STEMI and those with SAP (66 ± 12% vs 65 ± 10%, respectively; p = NS), but was slightly larger in patients with non-STEMI/UAP (71 ± 12%; p <0.05 vs both STEMI and SAP). In patients with STEMI, only 11% of culprit stenoses were found to have diameter stenosis <50% after removal of the thrombus. In conclusion, most STEMIs occurred at the site of severe coronary stenosis. Diameter stenosis severity was <50% in a minority of cases.

 

Historically, it was believed that the tighter the stenosis, the higher the risk of thrombotic occlusion.1, 2, 3 Recently, it was suggested that acute coronary syndromes predominantly occurred at the site of coronary stenoses <50% diameter reduction.4 Moreover, rupture of a thin-cap fibroatheroma was shown to be the underlying mechanism of many, albeit not all, acute coronary occlusions.5 Taken together, these findings were expanded into the general belief that mild stenoses with a thin fibrous cap were potentially more dangerous than tight ones. This notion in turn has led to proposing plaque sealing6 of mild stenoses to prevent their spontaneous rupture, despite the large amount of data showing the very favorable natural history of nonsignificant stenoses.7, 8 Several techniques have focused on the composition of the vessel wall in the vicinity of the occlusion site, but little attention has been given to date to the degree of luminal narrowing of these vulnerable plaques. Recent data from Frøbert et al9 obtained during primary percutaneous coronary intervention (PCI) suggested that the severity of stenosis responsible for myocardial infarction was >50% in diameter in most cases. Accordingly, using quantitative coronary angiography, we analyzed the severity of the stenosis responsible for acute ST-elevation myocardial infarction (STEMI) after successful thrombus aspiration.

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Methods 

A total of 317 patients belonging to the 3 groups defined according to clinical presentation were included in this prospective study of (1) 102 consecutive patients with STEMI referred for primary PCI, (2) 135 patients with non-STEMI or unstable angina pectoris (UAP) referred for semiurgent PCI, and (3) 80 patients with stable angina pectoris (SAP) admitted for elective coronary angioplasty.

The STEMI group consisted of patients strictly meeting the 4 criteria of (1) onset of symptoms ≥30 minutes and ≤12 hours before admission to the hospital; (2) ST elevation ≥2 mm in 2 contiguous precordial leads or ≥1 mm in 2 contiguous limb leads or new left branch bundle block; (3) a culprit lesion clearly defined on the basis of the combination of electrocardiographic and coronary angiographic findings (only patients with Thrombolysis In Myocardial Infarction [TIMI] grade 0 or 1 flow were included); and (4) TIMI grade 2 or 3 flow after successful thrombus aspiration. The non-STEMI/UAP group consisted of patients meeting the criteria of (1) angina at rest, new-onset severe angina (<2 months), or increasing angina (increasing in intensity, duration, and/or frequency) with or without troponin increase; and (2) a clearly identified culprit lesion on the basis of the combination of electrocardiographic and coronary angiographic findings (only patients with TIMI grade 2 or 3 flow were included). These patients did not undergo coronary aspiration. The SAP group consisted of patients with angina and no change in frequency, duration, or intensity of symptoms within 4 weeks before the intervention. As with the non-STEMI/UAP group, no aspiration was performed. Informed consent was obtained from all patients.

The STEMI group of patients underwent selective coronary angiography to define the culprit lesion. After wiring the culprit vessel, several runs of thrombus aspiration was performed using a 6-Fr Export XT catheter (Medtronic, Minneapolis, Minnesota). On restoration of TIMI flow grade 2 or 3, intracoronary nitrates were given (isosorbide dinitrate 200 μg) and a biplane high-quality angiogram was acquired. Thereafter, primary PCI was performed using standard methods. A biplane left ventricular angiogram was obtained in all patients to determine left ventricular end-diastolic and systolic volumes, ejection fraction, and systolic wall motion.

In patients with non-STEMI/UAP and SAP, biplane left ventriculography and high-quality coronary biplane angiography were performed after intracoronary administration of nitrates. Thereafter, PCI of the target vessel was performed using established methods.

The computer-based ACOM PC 5.01 (Siemens Medical Systems, Inc., Erlangen, Germany) was used for off-line quantitative coronary angiography analysis. Measurements were performed in end-diastole, preferably in 2 orthogonal projections or, if this could not be obtained, in the projection that best showed the diseased segment with as little foreshortening as possible. Minimal lumen diameter (millimeters), lumen diameter stenosis (percent), and reference diameter (millimeters) were measured after thrombus aspiration in the STEMI group and before PCI in the non-STEMI/UAP and SAP groups. One experienced cardiologist blinded to patient identity and group reviewed and examined all angiographic data. In our laboratory, intra- and interobserver variability for minimal lumen diameter on repeated analysis of the same frame were 0.11 and 0.08 mm, respectively.10

Statistical analysis was performed using GraphPad Prism 5 Software (La Jolla, California). Continuous variables were presented as mean ± SD. Pearson's bivariate correlation test was used for correlation of continuous variables. Categorical variables were expressed as frequencies and percentages. One-way analysis of variance and post hoc analysis using Bonferroni's test were applied to assess statistical significance in continuous variables. Chi-square test was used for comparison of categorical variables. A p values >0.05 was considered statistically nonsignificant.

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Results 

Main clinical characteristics of the 3 groups of patients are listed in Table 1. Patients presenting with STEMI were significantly younger and had less arterial hypertension compared with patients with non-STEMI/UAP or SAP. Although left ventricular ejection fraction of patients with STEMI was on average in the normal range, it was still significantly lower than in the 2 other groups of patients.

Table 1. Patient characteristics
VariableSAP (n = 80)Non-STEMI/UAP (n = 135)STEMI (n = 102)
Age (yrs)67±1070±1059±11⁎
Men/women56/2498/3778/24
Body mass index (kg/m2)27±327±428±5
Smoker42%52%56%
Arterial hypertension†58%53%37%⁎
Diabetes mellitus19%20%16%
Hyperlipidemia‡61%63%52%
Ejection fraction (%)69±15%73±11%63±14%⁎

⁎p <0.05 versus non-STEMI and SAP.

†Systolic arterial blood pressure ≥140 mm Hg and/or diastolic pressure ≥90 mm Hg.

‡Low-density lipoprotein cholesterol ≥100 mg/dl.

Main angiographic data for the 3 groups are listed in Table 2. Incidences of left anterior descending and right and left circumflex coronary arterial stenoses were equally distributed among the 3 groups of patients. Although diameter stenosis and minimal lumen diameter were similar in patients presenting with STEMI (after aspiration of the thrombus) or SAP, diameter stenosis was significantly larger and minimal lumen diameter was significantly smaller in patients with non-STEMI/UAP. Reference diameters were similar in the 3 groups. The plot of individual data for the diameter of stenosis is shown in Figure 1. Most patients with STEMI had a high degree of stenosis (Figure 2) after thrombus removal, whereas only 11% had lesions <50% (Figure 3, Figure 4). In patients with STEMI, no significant difference was found between diabetic and nondiabetic patients in terms of diameter stenosis or minimal lumen diameter. No clinical characteristic correlated with severity of the underlying stenosis.

Table 2. Angiographic data before percutaneous coronary intervention
VariableSAP (n = 80)Non-STEMI/UAP (n = 135)STEMI (n = 102)
Left anterior descending coronary artery48%37%40%
Left circumflex coronary artery18%30%11%
Right coronary artery33%24%46%
Other coronary vessel1%9%3%
Diameter stenosis (%)64±12%72±11%⁎66±12%
Minimal lumen diameter (mm)1±0.40.7±0.4⁎0.93±0.4
Reference diameter (mm)2.7±0.62.7±0.72.7±0.6

⁎p <0.05 versus STEMI and SAP.

  • View full-size image.
  • Figure 2. 

    Left coronary angiogram from a 53-year-old patient with acute anterior myocardial infarction (A) before thrombus aspiration, (B) after aspiration of a 12 × 1-mm large thrombus, and (C) the aspirated thrombus.

  • View full-size image.
  • Figure 3. 

    Left coronary angiogram from a 67-year-old patient with acute inferolateral myocardial infarction (A) before and (B) after thrombus aspiration and (C) the aspirated thrombus.

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Discussion 

In this study, angiographic assessment of lesion severity was objectively quantified in patients with acute myocardial infarction after aspiration of the occlusive thrombus. Data suggested that STEMI predominantly occurred at sites with angiographic diameter stenosis >50%. Only approximately 10% of patients with STEMI had a culprit lesion with diameter stenosis <50% after aspiration of thrombus material. Similarly, in patients with non-STEMI/UAP, in whom aspiration was not performed, diameter stenosis was predominantly >50%. Earlier angiographic studies had suggested that culprit lesions typically had <50% diameter stenosis before the acute coronary events.11, 12, 13, 14, 15 However, in these small retrospective studies, the interval between the index angiogram and acute coronary syndrome was often very long. Some figures derived from intravascular ultrasound indicated that plaque ruptures occurred at sites of significant plaque accumulation with positive remodeling, but that the degree of lumen compromise was highly variable and often insignificant.16

In addition, plaque ruptures were identified in nonculprit arteries in approximately 2/3 of patients presenting with acute coronary syndrome and 1/3 of patients with SAP.17, 18 Furthermore, thin-cap fibroatheroma was frequently detected using ultrasound radiofrequency data analysis in nonculprit nonobstructive lesions in patients with SAP and UAP.19 Because ruptured thin-cap fibroatheroma was identified as the precipitating factor for 60% of occlusive coronary thrombosis,20 these findings led to the misconception that acute events occurred at the site of nonobstructive lesions, a concept at odds with histopathologic studies from patients with coronary death that showed that at the site of plaque rupture with superimposed thrombus, the underlying lesions were severe.21

However, thin-cap fibroatheroma or even plaque rupture did not necessarily lead to symptoms. In data by Rioufol et al,17 20 of 24 ruptured plaques (83%) responsible for an acute coronary event had a cross-sectional area <3 mm2 (Gilles Rioufol, April 2007, personal communication). Similarly, Fujii et al18 showed that lumen cross-sectional area was significantly smaller and area stenosis, plaque burden, and lesion length were significantly larger in culprit versus nonculprit ruptured plaques, respectively. In addition, similar lumen cross-sectional areas were found in stenoses related to acute myocardial infarction and those responsible for exercise-induced ischemia.22 Taken together, these data suggested that plaque rupture led to symptoms predominantly when occurring at the level of a “significant” stenosis. The association of plaque rupture with smaller lumen area and thrombus formation caused lumen compromise and led to symptoms. Furthermore, a tight stenosis appeared to be a condition sine qua non for abrupt occlusion. Recently, Ojio et al23 investigated a group of 20 patients who underwent angiography within 1 week before an acute myocardial infarction, at a time when a significant thrombus burden was not present and TIMI flow was normal. In all patients, >50% diameter stenosis was found at quantitative coronary angiography. Similarly, Frøbert et al9 investigated 250 consecutive patients referred for primary PCI. Upon flow restoration (spontaneously or after “wiring” of the vessel), the investigators found angiographically critical stenosis in virtually all patients. However, in this study, persistent thrombus may have led to overestimation of the severity of the underlying stenosis.

Few studies have investigated the risk of coronary events as a function of coronary stenosis severity. In the Coronary Artery Surgery Study (CASS) Registry,24 individual risk of occlusion in each coronary segment after 5 years was found to be almost exponentially proportional to its stenosis severity at baseline. Similarly, Abizaid et al25 found that the risk of cardiac events after 1 year related to untreated lesions was inversely proportional to the cross-sectional area at baseline. These data suggested that the tighter the coronary narrowing, the worse the outcome. Glaser et al26 also confirmed that <6% of patients undergoing PCI had to undergo a second intervention in a nontarget lesion. In addition, 2/3 of these lesions were already considered “significant” at the time of the initial procedure.26 This was confirmed in the randomized DEFER Study, in which the annual risk of death and/or myocardial infarction during 5 years was found to be very low (<1%) in patients with hemodynamically nonsignificant stenosis (fractional flow reserve ≥0.75), but was almost 5 times larger in case of hemodynamically significant stenosis (fractional flow reserve <0.75) that underwent PCI.27 In addition, the natural history of ruptured plaques not causing significant luminal compromise seemed to be very favorable, shown using both intravascular ultrasound28 and coronary angioscopic29 studies.

Therefore, in contrast to the notion that most plaque ruptures resulting in abrupt coronary occlusion occurred in stenoses <50%, clinical outcome related to mild coronary stenosis appeared favorable and did not seem to justify mechanical interventions to prevent spontaneous occlusion.

A number of limitations should be taken into account. (1) In the present study, thrombus aspiration was performed to analyze the underlying lesion. Only patients in whom TIMI flow 2 or 3 was reestablished were included in the study. However, it was unlikely that all thrombi had been completely removed. Therefore, residual material within the segment may have led to overestimation of stenosis severity in patients with STEMI. (2) Patients with sudden death who never reach the hospital were excluded de facto from this study. This might have led to selection bias because it could be speculated that these patients may have had less pronounced stenosis and therefore less ischemia in daily life and, in turn, less preconditioning and no collaterals. (3) Thrombus aspiration was performed in only patients with STEMI. Because thrombus formation was also present in patients with unstable syndromes, this might have led to overestimation of stenosis severity in patients with non-STEMI/UAP and might explain why in this study a larger percentage of diameter stenosis was found in the latter group. (4) The present data focused on lesion dimensions only during the acute phase. The fate of the severity of narrowing cannot be derived from the present data. Ojio et al23 suggested that lesions that led to infarction underwent rapid progression during the last year preceding the occlusion. (5) Use of angiography instead of more accurate methods, such as intravascular ultrasound or fractional flow reserve, may have led to overestimation of some stenoses and underestimation of others.30 However, the same method was applied to the 3 groups of patients.

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PII: S0002-9149(09)00126-X

doi:10.1016/j.amjcard.2008.12.047

American Journal of Cardiology
Volume 103, Issue 9 , Pages 1183-1188, 1 May 2009

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