Impact of a Chronic Total Occlusion in a Non-Infarct Related Artery on Clinical Outcomes Following Primary Percutaneous Intervention in Acute ST-Elevation Myocardial Infarction

Abstract: Aims. We aimed to assess the impact of a non-infarct related artery (IRA) chronic total occlusion (CTO) on clinical outcomes following primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) in a real-world cohort of patients. Methods and Results. This is a retrospective observational study of 1435 patients treated at a large single tertiary cardiac center providing a high-volume PPCI service. Patients with coexisting CTO (4.7%) were significantly more likely to have presented in cardiogenic shock and less likely to achieve TIMI 2/3 flow in the IRA post procedure resulting in lower ejection fraction and higher peak troponin-T levels. A concurrent CTO in a non-IRA was associated with higher in-hospital mortality (16.4% vs 3.1%; P<.001), 30-day mortality (19.4% vs 5.9%; P<.001) and long-term mortality (23.9% vs 12.2%; P=.01). Binary logistic regression analysis showed that the presence of a non-IRA CTO was independently predictive of mortality at 30 days (odds ratio, 3.2; 95% confidence interval, 1.2-8.1) but not for long-term mortality. Conclusion. The presence of a coexisting CTO in patients undergoing PPCI for STEMI is associated with adverse clinical outcomes; further work is required to improve prognosis in these patients, which may include early staged revascularization of the non-IRA CTO.   

J INVASIVE CARDIOL 2014;26(1):13-16

Key words: chronic total occlusion, primary PCI, STEMI

____________________________

Primary percutaneous coronary intervention (PCI) has improved the short- and long-term clinical outcomes in patients with ST-elevation myocardial infarction.¹ However, subgroups of patients continue to have higher than desirable mortality rates. In particular, observational studies have shown worse outcomes in patients presenting with multi-vessel disease including a non-infarct related artery (non-IRA) chronic total occlusion (CTO).^2,3 However, it remains unclear whether any additional clinical benefit is derived from multivessel revascularization in the acute setting.⁴ This is reflected in international guidance discouraging PCI of non-IRA lesions at the time of primary PCI.⁵ 

The aim of this retrospective study is to evaluate the impact of a non-IRA CTO on short- and long-term clinical outcomes in a real-world population of patients undergoing primary PCI at a single tertiary center in the United Kingdom.

Methods

This is a single-center retrospective observational study from a high-volume primary PCI tertiary cardiac center in the United Kingdom. 

A total of 1435 consecutive patients who underwent primary PCI between September 2009 and November 2011 were included in the study. Thirty-six patients were excluded from the study, having undergone previous coronary artery bypass grafting (CABG). Patients’ demographic and clinical data were obtained from our Cardiac Services Database System (Phillips CVIS). All patients underwent transthoracic echocardiography on day 1 post PCI and peak troponin-T level was obtained from blood tests taken during the inpatient stay. Mortality data were gathered from the United Kingdom Office of National Statistics. The mean follow-up period was 2.1 years. 

The parametric 2-sided t-test and chi-squared test were used for statistical comparisons of continuous and categorical variables respectively. Binary logistic regression was used to assess for independent predictors of short- and long-term mortality. A P-value of <.05 was considered to indicate statistical significance. 

Results

Of the 1435 patients who underwent primary PCI, sixty-seven (4.7%) were identified as having a CTO in a non-infarct related artery (Table 1). Patients with and without a coexisting CTO were similar with regard to age, history of hypertension, and hypercholesterolemia (Table 1). Patients with coexisting CTO were significantly more likely to be male (83.6% vs 71.9%; P=.03), diabetic (20.9% vs 10.5%; P=.01), and have a past history of myocardial infarction (19.4% vs 10.4%; P=.02) when compared to those without CTOs (Table 1). 

Those with a coexisting CTO were also significantly more likely to have presented in cardiogenic shock (22.4% vs 7.0%; P<.001) and to require resuscitation from cardiac arrest during the procedure (6.0% vs 2.0% P=.02) (Table 2). Successful reperfusion, judged by achievement of TIMI 2/3 flow in the infarct-related artery, and ejection fraction (on echocardiogram day 1 post admission) were lower in those with a coexisting CTO (Table 2). Peak troponin-T level was significantly higher in patients with a CTO, suggesting a larger final infarct size.

The presence of an additional significant coronary artery lesion (greater than 75% stenosis) was lower in patients with a coexisting CTO (8.9% vs 25.8%; P=.01) and non-IRA PCI during the index procedure was numerically greater in those without a coexisting CTO (8.1% vs 3.1%; P=.61).

Most importantly, a concurrent CTO in a non-infarct related artery was linked with poor short- and long-term clinical outcomes. This was reflected by higher in-hospital mortality (16.4% vs 3.1%; P<.001), 30-day mortality (19.4% vs 5.9%; P<.001) (Figure 1) and long-term mortality (23.9% vs 12.2%; P=.01; mean follow-up period, 2.1 years) (Figure 2). Long-term survival, analyzed by Kaplan-Meier analysis, was significantly lower in patients with a coexisting CTO (Figure 3). 

Binary logistic regression analysis showed that the presence of non-IRA CTO was independently predictive of mortality at 30 days (OR, 3.2; 95% CI, 1.2-8.1) but not for long-term mortality (Table 3).  

Discussion

In this retrospective analysis of 1435 consecutive patients undergoing primary PCI, a non-IRA CTO was present in 4.7% of patients presenting with STEMI. The presence of a CTO independently predicted mortality at 30 days with a three-fold increase in risk.

The current analysis, drawn from a large single-center study, confirms previous reports demonstrating poor prognosis associated  with the presence of a CTO in a non-IRA in patients undergoing  primary PCI for acute STEMI.^2,6 The mechanisms underlying the increased mortality are likely to be multifactorial. Patients with CTOs have a higher prevalence of comorbidities, including diabetes and previous myocardial infarction; nevertheless, the presence of a CTO was an independent predictor of 30-day mortality in our study.

A possible explanation is larger completed infarct size in patients with a CTO in a non-IRA, particularly if the distal coronary bed of the CTO artery depends upon collateral blood flow from the IRA. In this situation, the area at risk of the IRA territory would extend beyond its own supply territory and extend to the collateralized non-IRA CTO area. The significantly higher peak troponin-T level and lower ejection fraction, seen in patients with a coexisting CTO in our study, supports this hypothesis. A trend toward a greater infarct size, measured by peak creatinine phosphokinase levels, was also seen in patients with a coexisting CTO in a substudy analysis of the HORIZONS-AMI study. 

Another possible explanation is the lack of collateral flow to the distal bed of the acutely occluded coronary artery due to the coexisting CTO, which may lead to microvascular ischemia, increased reperfusion injury, and delayed healing. This hypothesis is supported by lower rates of TIMI 2/3 flow achieved in patients with a coexisting CTO in our study. Further evidence is provided by the reduced myocardial blush grade and ST-segment resolution seen in patients with a non-IRA CTO in a substudy analysis of the TAPAS study.⁷

Our study differs from previous studies in demonstrating an independent mortality risk associated with a coexisting CTO only at 30 days and not during long-term follow-up. This finding may have important clinical implications, since it suggests that if any staged revascularization is to be performed, it needs to be carried out within 30 days to impact on mortality. There are currently relatively scarce data to support such an approach and in fact several studies of multi-vessel PCI in the STEMI setting have demonstrated increased morbidity without any clinical benefit.^8-11 However, a recent observational study of 136 patients with a non-IRA CTO demonstrated that successful recanalization of the CTO between 7-10 days after STEMI was an independent predictor for 2-year cardiac mortality (hazard ratio [HR]=0.145; 95% CI, 0.047-0.446; P=.01) and event-free survival (HR=0.430; 95% CI, 0.220-0.838; P=.01).¹² This finding is currently being further examined in the ongoing EXPLORE (evaluating Xience V and left ventricular function in percutaneous coronary intervention on occlusions after ST-elevation myocardial infarction) trial, which is a prospective randomized study investigating whether revascularization of a non-IRA CTO within 1 week of primary PCI, compared with optimal medical therapy, is associated with beneficial effects on left ventricular dimensions and function.¹³  

Finally, the demonstration of an adverse clinical outcome in patients with a non-IRA CTO raises the possibility that PCI of a CTO in patients with stable angina may be protective in the event of a future acute infarct. A CTO is identified in 15%-30% of patients undergoing diagnostic angiography,^14,15 although only a relatively small proportion of these patients are referred for PCI.¹⁶ Historically, an antegrade-only approach to CTO recanalization was associated with a success rate of 60%-70%.¹⁷ However, with the advent of novel techniques such as antegrade dissection re-entry and retrograde approach, the success rate has improved to 80%-90% in high-volume centers.^18,19 Several observational studies have demonstrated improved clinical outcomes in stable patients undergoing revascularization of a CTO.^17,20

Study limitations. This is a retrospective analysis of primary PCI cases from a single center. The limitations are therefore lack of prospective follow-up with regard to symptoms and quality of life. However, the strength of the study lies in the short- and long-term mortality data from a large cohort of patients. 

Conclusion

Our results confirm recent data demonstrating the adverse effect of a coexisting CTO on clinical outcomes in patients with STEMI. Further work is needed to establish whether clinical benefit could be achieved by attempting staged revascularization of non-infarct related artery CTOs and at what time point this revascularization should occur. Finally, one could hypothesize that treating CTOs in stable patients may protect them from adverse outcomes if they were to present at a later date with acute myocardial infarction.

References

1. Terkelsen CJ, Jensen LO, Tilsted HH, et al. Primary percutaneous coronary intervention as a national reperfusion strategy in patients with ST-segment elevation myocardial infarction. Circ Cardiovasc Interv. 2011;4(6):570-576.
2. Claessen BE, Dangas GD, Weisz G, et al. Prognostic impact of a chronic total occlusion in a non-infarct-related artery in patients with ST-segment elevation myocardial infarction: 3-year results from the HORIZONS-AMI trial. Eur Heart J. 2012;33(6):768-775.
3. Hoebers LP, Vis MM, Claessen BE, et al. The impact of multivessel disease with and without a coexisting chronic total occlusion on short- and long-term mortality in ST-elevation myocardial infarction patients with and without cardiogenic shock. Eur J Heart Fail. 2013;15(4):425-432.
4. Sethi A, Bahekar A, Bhuriya R, Singh S, Ahmed A, Khosla S. Complete versus culprit only revascularization in acute ST-elevation myocardial infarction: a meta-analysis. Catheter Cardiovasc Interv. 2011;77(2):163-170.
5. Steg PG, James SK, Atar D, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33(20):2569-2619.
6. Claessen BE, van der Schaaf RJ, Verouden NJ, et al. Evaluation of the effect of a concurrent chronic total occlusion on long-term mortality and left ventricular function in patients after primary percutaneous coronary intervention. JACC Cardiovasc Interv. 2009;2(11):1128-1134.
7. Lexis CP, van der Horst IC, Rahel BM, et al. Impact of chronic total occlusions on markers of reperfusion, infarct size, and long-term mortality: a substudy from the TAPAS-trial. Catheter Cardiovasc Interv. 2011;77(4):484-491.
8. Cavender MA, Milford-Beland S, Roe MT, Peterson ED, Weintraub WS, Rao SV. Prevalence, predictors, and in-hospital outcomes of non-infarct artery intervention during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (from the National Cardiovascular Data Registry). Am J Cardiol. 2009;104(4):507-513.
9. Chen LY, Lennon RJ, Grantham JA, et al. In-hospital and long-term outcomes of multivessel percutaneous coronary revascularization after acute myocardial infarction. Am J Cardiol. 2005;95(3):349-354.
10. Corpus RA, House JA, Marso SP, et al. Multivessel percutaneous coronary intervention in patients with multivessel disease and acute myocardial infarction. Am Heart J. 2004;148(3):493-500.
11. Kornowski R, Mehran R, Dangas G, et al. Prognostic impact of staged versus “one-time” multivessel percutaneous intervention in acute myocardial infarction: analysis from the HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trial. J Am Coll Cardiol. 2011;58(7):704-711.
12. Yang ZK, Zhang RY, Hu J, Zhang Q, Ding FH, Shen WF. Impact of successful staged revascularization of a chronic total occlusion in the non-infarct-related artery on long-term outcome in patients with acute ST-segment elevation myocardial infarction. Int J Cardiol. 2013;165(1):76-79.
13. van der Schaaf RJ, Claessen BE, Hoebers LP, et al. Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction. Trials. 2010;11:89.
14. Kahn JK. Angiographic suitability for catheter revascularization of total coronary occlusions in patients from a community hospital setting. Am Heart J. 1993;126(3 Pt 1):561-564.
15. Christofferson RD, Lehmann KG, Martin GV, Every N, Caldwell JH, Kapadia SR. Effect of chronic total coronary occlusion on treatment strategy. Am J Cardiol. 2005;95(9):1088-1091.
16. Anderson HV, Shaw RE, Brindis RG, et al. A contemporary overview of percutaneous coronary interventions. The American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR). J Am Coll Cardiol. 2002;39(7):1096-1103.
17. Joyal D, Afilalo J, Rinfret S. Effectiveness of recanalization of chronic total occlusions: a systematic review and meta-analysis. Am Heart J. 2010;160(1):179-187.
18. Galassi AR, Tomasello SD, Costanzo L, Campisano MB, Barrano G, Tamburino C. Long-term clinical and angiographic results of Sirolimus-Eluting Stent in Complex Coronary Chronic Total Occlusion Revascularization: the SECTOR registry. J Interv Cardiol. 2011;24(5):426-436.
19. Thompson CA, Jayne JE, Robb JF, et al. Retrograde techniques and the impact of operator volume on percutaneous intervention for coronary chronic total occlusions an early U.S. experience. JACC Cardiovasc Interv. 2009;2(9):834-842.
20. Jones DA, Weerackody R, Rathod K, et al. Successful recanalization of chronic total occlusions is associated with improved long-term survival. JACC Cardiovasc Interv. 2012;5(4):380-388.