|
 
 |
| ORIGINAL ARTICLE |
|
| Year : 2021 | Volume
: 10
| Issue : 3 | Page : 95-101 |
|
Coronary collateral circulation in acute, subacute, and chronic total occlusions
Ashida Thulaseedharan Sarojadevi MD, DNB (Cardiology) 1, Vinayagamoorthy Venugopal MD 2
1 Department of Cardiology, Sri Manakulavinayagar Medical College and Hospital, Puducherry, India
2 Department of Community Medicine, Sri Manakulavinayagar Medical College and Hospital, Puducherry, India
| Date of Submission | 22-Jan-2021 |
| Date of Acceptance | 23-Jun-2021 |
| Date of Web Publication | 23-Sep-2021 |
Correspondence Address:
Dr. Ashida Thulaseedharan Sarojadevi
Department of Cardiology, Sri Manakulavinayagar Medical College and Hospital, Puducherry
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jcpc.jcpc_5_21
Context: A study on the pattern of coronary collateral circulation is relevant in coronary artery disease (CAD) where despite advances in revascularization, the prevalence of heart failure is increasing. Aims: The aim was to study the pattern of coronary collateral circulation in acute, subacute, and chronic coronary total occlusions and to find out the association between collateral grade with the severity of CAD. Settings and Design: This was a hospital-based retrospective cross-sectional study of 141 patients with acute, subacute, or chronic total occlusion of coronaries detected by coronary angiography. Subjects and Methods: Data of 141 patients with total occlusion of coronaries detected by coronary angiography were analyzed. Collateral grading was done according to the Rentrop classification and Werner classification. The severity of CAD was assessed using Gensini score and Syntax score. Pattern of collateral circulation in different types of coronary occlusions and the association between collateral grade and severity of CAD were assessed. Statistical Analysis Used: The association of categorical clinical and angiographic features with type of occlusion was tested using Chi-square test and that of continuous variable with student t-test. All tests were two tailed and P < 0.05 was considered statistically significant. Results: Young patients presented predominantly with acute coronary occlusions (82.6%). About 73% of the patients with left ventricle (LV) dysfunction had acute coronary occlusions. Nearly 68.8% of patients with poor Rentrop collateral grades had LV dysfunction. Patients with acute occlusion had low atherosclerotic burden as evidenced by lower Gensini and Syntax scores and had poor coronary collaterals. No significant correlation was seen between Gensini and Syntax scores and collateral grade. Patients who presented with ST-elevation myocardial infarction (STEMI) had poor Rentrop collaterals and higher prevalence of single-vessel disease and double-vessel diseases when compared to those with non-ST-segment elevation acute coronary syndrome and chronic stable angina. Conclusions: Young male patients with low atherosclerotic burden tend to present with acute coronary occlusions. This subgroup has poor collateral circulation and LV dysfunction. No statistically significant difference was seen in the presence of diabetes, hypertension, number of epicardial coronary artery involvement, or the severity of CAD in the STEMI patients with good or poor Rentrop collaterals.
Keywords: Coronary artery disease, coronary collateral connection, ejection fraction, Rentrop grade, Syntax score, Werner collateral grade
How to cite this article:
Sarojadevi AT, Venugopal V. Coronary collateral circulation in acute, subacute, and chronic total occlusions. J Clin Prev Cardiol 2021;10:95-101 |
| Introduction | |  |
Normal human heart contains small interconnecting anastomotic vessels which serve as the precursors of collateral circulation.[1] Angiographically, visible coronary collaterals develop when significant stenosis in a coronary artery creates a transanastomotic pressure gradient. Hence as a group, patients with collateral circulation are expected to have more severe coronary artery disease (CAD). A well-developed collateral circulation has been shown to reduce myocardial ischemia, maintain myocardial viability, and reduce the extent of myocardial damage during acute coronary occlusion.[2],[3],[4]
In developing countries like India with a high burden of CAD, patients often tend to present late, delaying reperfusion therapy, thus resulting in significant myocardial damage.[5] Hence a study on the pattern of coronary collateral circulation is relevant in CAD, as current systems do not take into account the analysis of collateral circulation anatomy. The aim of our study was to describe the pattern of coronary collateral circulation in acute, subacute, and chronic coronary total occlusions and to find out the association between collateral grade with the severity of CAD.
| Subjects and Methods | | |
This was a hospital-based retrospective cross-sectional study carried out in the Department of Cardiology in Sri Manakula Vinayagar Medical College and Hospital, a tertiary care teaching hospital in Pondicherry. The hospital with more than 900 beds offers preventive and curative services to the population of rural Pondicherry and Villupuram district.
Records from the catheterization laboratory of the cardiology Department were assessed after obtaining approval from the Institute Ethical Committee. Records having incomplete information were excluded.
Operational definitions
Coronary occlusions were classified as chronic total occlusions as those occluded coronary arteries with a documented duration of occlusion of at least 3 months with absolutely no flow through the lesion (TIMI 0 flow). Occlusions within 1–3 months were addressed as recent occlusions and within 4 weeks as acute occlusions.[6] The duration of the occlusion was determined from a previous angiogram, the date of a previous myocardial infarction, or from the onset of symptoms.
Collateral grading
Collateral grading was done by two blinded investigators who evaluated the angiographic images independently and in the case of disagreement, a consensus was obtained. The coronary collateral connection (CCC) was graded according to the Rentrop classification which describes the collaterals according to their effect in filling the occluded arterial segment.[7] Accordingly, Grade 0 was classified as no filling; Grade 1 classified as filling of side branches via collateral channels without visualization of the epicardial segment; Grade 2 classified as a partial filling of epicardial major coronary artery via collateral channels; and Grade 3 classified as complete filling of epicardial major coronary artery. In patients with more than one coronary lesion, and when there was more than one CCC, the CCC with the highest Rentrop was used. Rentrop Grade 0/1 were classified as poor collaterals and Grades 2/3 were classified as good collaterals. Collateral grading was also done according to the semi-quantitative assessment of collaterals by Werner et al.[8] Collateral connection (CC) Grade 0 was defined as no continuous connection between collateral supplying and receiving vessel, CC1 as those with thread-like continuous connection, and CC2 as side branch-like connection.
Severity of coronary artery disease
Severity of CAD was assessed using Gensini score and Syntax score. A Gensini score >40 but ≤100 was defined as advanced CAD, and a Gensini score >100 was defined as heavy CAD. The Syntax score was divided into tertiles as low (<22), intermediate (22-32), and high (>33).
Statistical analysis
Data were entered in Epi data software version 4.2 and analyzed using SPSS (windows XP) software version 24. Description of the categorical variable was done in frequency and percentage and that of continuous variable in mean and standard deviation. The association of categorical clinical and angiographic features with type of occlusion was tested using Chi-square test and that of continuous variable using Student's t-test. All tests were two tailed and P < 0.05 was considered statistically significant.
| Results | | |
One hundred and forty-one patients fulfilled the eligibility criteria for inclusion into the study. Of these 141 patients, 41.8% were in the age category of 46 – 60 years and above 60 years each. The remaining 16.4% of them belonged to the age group of 30–45 years. Majority of them were male (84.4%) and the rest were female. Regarding the presentation of CAD, 32.6% presented with chronic stable angina, and 67.4% of the patients presented with acute coronary syndrome (ACS). Majority of patients (65.2%) had acute coronary occlusion, 31.9% had subacute occlusions, and 2.9% of patients had chronic total occlusions [Table 1].
On analyzing the sociodemographic and risk factors associated with duration of presentation of CAD, patients in the age group of 30–45 years had more acute occlusion (82.6), males had more acute occlusions (67.2%), but the difference in age and gender with type of occlusion was not significant. There was no significant association between duration of occlusion and presence of diabetes, hypertension, dyslipidemia, and smoking status. Patients with past CAD had less acute occlusion (16.7%) and more subacute (66.7%) and chronic (16.7%) occlusion compared with patients not having a past history of CAD. This difference was statistically significant.
About 63.8% of patients had left ventricle (LV) dysfunction (LV ejection fraction (EF] <50%). Nearly 31.9% had left main coronary artery involvement. Almost 83.7% had advanced or high CAD by Gensini scores. About 35.5% had intermediate or high Syntax scores. On grading the collaterals, 54.6% of angiograms showed good collateral circulation (Rentrop 2/3). Werner's CC2 collaterals were seen in only 22.7% of patients [Table 2]. | Table 2: Investigatory findings of coronary artery disease patients (n=141)
Click here to view |
Majority of the CAD patients with LV dysfunction presented with acute occlusion (73.3%) compared to those with EF >50 (51%). Single (71.9%) and double-vessel diseases (DVD) (81%) had more acute occlusion and those with triple-vessel disease had more subacute (39.7%) and chronic occlusion (6.3%) and these findings were statistically significant (P < 0.05). When compared to patients with subacute or chronic coronary occlusions, patients with acute occlusions had poor collaterals as per the Rentrop classification (73.4%vs. 58.4%), but this was not statistically significant [Table 3]. | Table 3: Comparison of ejection fraction, coronary artery involvement and collateral grade with type of coronary occlusion
Click here to view |
The patients with acute occlusion had lower Gensini score and Syntax score, whereas those who had chronic occlusion had higher scores. There was an increasing trend in these scores gradually from acute towards chronic occlusions. These differences were statistically significant [Table 4] and [Table 5]. | Table 4: Comparison of Gensini and Syntax scores with duration of coronary occlusion patients (n=141)
Click here to view |
 | Table 5: Correlation of Gensini and Syntax scores with collateral grade (n=141)
Click here to view |
On correlating adequacy of collateral circulation with EF, 68.8% of patients with poor Rentrop collateral grades had LV dysfunction (EF <50%). Similarly, patients with CC2 Werner grade collaterals had better EF than those with CC0 and CC1 collaterals [Table 6] and [Table 7]. | Table 6: Association between the type of Rentrop collateral grade and ejection fraction (n=141)
Click here to view |
 | Table 7: Association between Werner collateral grade and ejection fraction (n=123)
Click here to view |
Patients were divided into three groups, those who presented with ST-elevation myocardial infarction (STEMI), non-ST-segment elevation acute coronary syndrome (NSTEACS), and cross-sectional area (CSA), and data were analyzed. Patients who presented with STEMI were predominantly young males. Among the traditional risk factors, diabetes and hypertension were less prevalent in the STEMI group [Table 8]. More than 50% of STEMI patients had LV dysfunction (53.3%). STEMI patients also had poor Rentrop collaterals and higher prevalence of single-vessel disease and DVD when compared to those with NSTEACS and CSA [Table 9]. There was no statistically significant difference in the presence of diabetes, hypertension, number of epicardial coronary artery involvement, or the severity of CAD in the STEMI patients with good or poor Rentrop collaterals [Table 10]. | Table 8: Demographic features of patients according to coronary artery disease presentation
Click here to view |
 | Table 9: Comparison of investigatory findings in patients according to coronary artery disease presentation
Click here to view |
 | Table 10: Association between various risk factors and angiographic parameters with Rentrop collateral status among ST-segment-elevation myocardial infarction patients (n=52)
Click here to view |
| Discussion | | |
The timely delivery of reperfusion therapy for STEMI is a challenge in developing countries like India. A well-developed coronary collateral circulation should preserve LV function in the incidence of a coronary occlusion. In the Study by Ajayi et al., a significant positive correlation was seen between coronary collateral grades and mean EF calculated for the different collateral grades. LV myocardial perfusion was greater in patients with well-developed coronary collaterals and resulted in better preservation of LV function even in the face of an acute coronary event.[9]
Collateral grade and type of coronary occlusion
In this study, young males presented more (73.4%vs. 58.4%) commonly with acute coronary occlusions. On analyzing the coronary collateral circulation, poor collaterals were seen in majority of the patients with acute coronary occlusions. About 41.6% of patients with good Rentrop collaterals presented with subacute or chronic coronary occlusions.
A protective role of coronary collaterals in preserving myocardial function and prevention of LV aneurysm formation in the setting of severe coronary stenosis has been reported by various studies.[10],[11] On the contrary, studies by Banerjee et al. and Ilia et al. showed no protective role for coronary collaterals in the preservation of LV function in patients with significant CAD.[12],[13]
About 63.8% of patients had LV dysfunction. On correlating adequacy of collateral circulation with EF, patients with good Rentrop collaterals had better EF than those with poor collaterals. Similarly, patients with CC2 Werner grade collaterals had better EF than those with CC0 and CC1 collaterals.
Although statistically not significant, CAD patients with EF <55 had more acute occlusion (73.3%) compared to those with >50 (51%). This could be explained as majority of the patients with acute occlusions had poor collaterals, thus jeopardizing the LV function.
Collateral grade and severity of coronary artery disease
Coronary stenosis is the strongest known stimulus for collateral development. However, it is still unclear as to why some patients develop sufficient collateral circulation while others do not despite significant coronary stenosis. Association between multi-vessel disease and coronary collateral circulation has been reported by several studies. Börekçi et al. reported a higher Syntax score in patients with poor coronary collaterals.[14] Cetin et al. observed that in the poor coronary collateral group, Syntax score were significantly higher compared to the good coronary collateral group.[15] In this study, both Gensini score and Syntax score did not show any significant correlation with collateral grade. Although significant coronary stenosis is the key stimulator to start the development of coronary collaterals, it alone cannot explain the adequacy of collateral connections.
Presentation with ST-elevation myocardial infarction and coronary collaterals
Traditional risk factors were less common among STEMI patients and this could be due to the younger age at presentation. Out of the 52 STEMI patients, 51 had anterior wall myocardial infraction and left anterior descending (LAD) was the occluded artery. The presence of angiographically detectable collaterals, especially Rentrop Grade 2/3, has been shown to have a protective effect on enzymatic infarct size, microvascular perfusion of the myocardium, and pre- and postinterventional hemodynamic conditions in patients with acute ST-segment-elevation myocardial infarction treated with percutaneous coronary intervention (PCI), particularly if the infarct-related vessel is LAD.[16] Compared to patients with NSTEACS and CSA, patients with STEMI had a higher prevalence of poor coronary collaterals in this study and this could have an impact on their long-term prognosis.
Therapeutic implications
Collateral promoting therapy, especially for at-risk young patients with CAD, should be part of the therapeutic armamentarium. This may help in preserving LV function and improving quality of life and long-term prognosis.
A significant improvement in collateral flow index (CFI) was demonstrated in response to moderate- and high-intensity exercise performed for 10 h per week in patients with stable CAD in the EXCITE trial.[16] In another study, a three months of cardiac rehabilitation utilizing exercise-based regimen augmented coronary collateral supply to normal vessels, and also to previously stenosis arteries undergone PCI.[17]
Genes encoding pathways for angiogenesis have been related to the extent of preexisting collateral network as well as development of a functional collateral circulation.[18],[19],[20]
Various studies have shown promising results on gene therapy in CAD by promoting collateral development through the administration of angiogenic growth factors.
| Conclusions | | |
Although mortality from CAD is declining, the incidence of associated heart failure is rising. A well-developed coronary collateral circulation can reduce the extent of myocardial damage during acute coronary occlusions and may extend the time buffer for successful reperfusion. A good functional coronary collateral circulation long-term cardiac mortality is reduced to one-fourth compared with the situation without collateral supply.[21],[22]
Young male patients with low atherosclerotic burden tend to present with acute coronary occlusions. This subgroup has poor collateral circulation resulting in LV dysfunction unless revascularization is done in an emergent manner. Analyzing the adequacy of the coronary collateral circulation anatomically or via functional measurements like CFI will help to identify those with no or sparse endogenous collateral connections. Strategies aimed at augmenting collateral circulation are an attractive investigation subject, especially in young patients with CAD. Cardiac rehabilitation utilizing exercise-based regimens is often underutilized. Therapeutic angiogenesis by gene therapy, cell therapy, and their combination are promising areas of research in patients with poor functional collateral collaterals.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Baroldi G, Mantero O, Scomazzoni G. The collaterals of the coronary arteries in normal and pathologic hearts. Circ Res 1956;4:223-9.  |
| 2. | Fukai M, Ii M, Nakakoji T, Kawakatsu M, Nariyama J, Yokota N, et al. Angiographically demonstrated coronary collaterals predict residual viable myocardium in patients with chronic myocardial infarction: A regional metabolic study. J Cardiol 2000;35:103-11. |
| 3. | Sabia PJ, Powers ER, Ragosta M, Sarembock IJ, Burwell LR, Kaul S. An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction. N Engl J Med 1992;327:1825-31. |
| 4. | Simons PC, Algra A, van de Laak MF, Grobbee DE, van der Graaf Y. Second manifestations of ARTerial disease (SMART) study: Rationale and design. Eur J Epidemiol 1999;15:773-81. |
| 5. | Mohanan PP, Mathew R, Harikrishnan S, Krishnan MN, Zachariah G, Joseph J, et al. Kerala ACS Registry Investigators. Presentation, management, and outcomes of 25748 acute coronary syndrome admissions in Kerala, India: Results from the Kerala ACS Registry. Eur Heart J 2013;34:121-9. |
| 6. | Di Mario C, Werner GS, Sianos G, Galassi AR, Büttner J, Dudek D, et al. European perspective in the recanalisation of Chronic Total Occlusions (CTO): Consensus document from the EuroCTO Club. EuroIntervention 2007;3:30-43. |
| 7. | Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985;5:587-92. |
| 8. | Werner GS, Ferrari M, Heinke S, Kuelhe F. Angiographic assesment of collateral connections in comparison with invasively determined collateral function in chronic coronary occlusions. Circulation 2003;107:1972-7. |
| 9. | Ajayi NO, Vanker EA, Satyapal KS. The role of coronary artery collaterals in the preservation of left ventricular function: A study to address a long-standing controversy. Cardiovasc J Afr 2017;28:81-5. |
| 10. | Heaps CL, Parker JL. Effects of exercise training on coronary collateralization and control of collateral resistance. J Appl Physiol (1985) 2011;111:587-98. |
| 11. | Hirai T, Fujita M, Nakajima H, Asanoi H, Yamanishi K, Ohno A. et al. Importance of collateral circulation for prevention of left ventricular aneurysm formation in acute myocardial infarction. Circulation 1989;79:791-6. |
| 12. | Banerjee AK, Madan Mohan SK, Ching GW, Singh SP. Functional significance of coronary collateral vessels in patients with previous 'Q' wave infarction: Relation to aneurysm, left ventricular end diastolic pressure and ejection fraction. Int J Cardiol 1993;38:263-71. |
| 13. | Ilia R, Carmel S, Cafri C, Gueron M. Coronary collaterals in patients with normal and impaired left ventricular systolic function. Int J Cardiol 1998;63:151-3. |
| 14. | Börekçi A, Gür M, Seker T, Baykan AO, Özaltun B, Karakoyun S. Coronary collateral circulation in patients with chronic coronary total occlusion; its relationship with cardiac risk markers and SYNTAX score. Perfusion 2015;30:457-64. |
| 15. | Cetin MS, Ozcan Cetin EH, Balci KG, Aydin S, Ediboglu E, Bayraktar MF. The association between whole blood viscosity and coronary collateral circulation in patients with chronic total occlusion. Korean Circ J 2016;46:784-90. |
| 16. | Elsman P, van 't Hof AW, de Boer MJ, Hoorntje JC, Suryapranata H, Dambrink JH, et al. Role of collateral circulation in the acute phase of ST-segment-elevation myocardial infarction treated with primary coronary intervention. Eur Heart J 2004;25:854-8. |
| 17. | Möbius-Winkler S, Uhlemann M, Adams V, Sandri M, Erbs S, Lenk K, et al. Coronary collateral growth induced by physical exercise: Results of the impact of intensive exercise training on coronary collateral circulation in patients with stable coronary artery disease (EXCITE) trial. Circulation 2016;133:1438-48. |
| 18. | Zbinden R, Zbinden S, Meier P, Hutter D, Billinger M, Wahl A, et al. Coronary collateral flow in response to endurance exercise training. Eur J Cardiovasc Prev Rehabil 2007;14:250-7. |
| 19. | Tuttle JL, Nachreiner RD, Bhuller AS, Condict KW, Connors BA, Herring BP, et al. Shear level influences resistance artery remodeling: Wall dimensions, cell density, and eNOS expression. Am J Physiol Heart Circ Physiol 2001;281:H1380-9. |
| 20. | Risau W. Mechanisms of angiogenesis. Nature 1997;386:671-4. |
| 21. | Hendel RC, Henry TD, Rocha-Singh K, Isner JM, Kereiakes DJ, Giordano FJ, et al. Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: Evidence for a dose-dependent effect. Circulation 2000;101:118-21. |
| 22. | Meier P, Gloekler S, Zbinden R, Beckh S, de Marchi SF, Zbinden S, et al. Beneficial effect of recruitable collaterals: A 10-year follow-up study in patients with stable coronary artery disease undergoing quantitative collateral measurements. Circulation 2007;116:975-83. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]
|
Search Pubmed for