CTRI

Protocol

1. Title of the project: INFLUENCE OF USE OF IVUS FOR DECISION MAKING DURING PRIMARY ANGIOPLASTY ON FINAL PROCEDURAL TIMI FLOW AND TMPG

2. Type of Study: Prospective study- cross sectional study

3. Aims & objectives : To assess the difference between TIMI flow, TFC and TMPG between IVUS group and non IVUS group.

Primary objective:

To assess the difference between TIMI flow, corrected TFC, TMPG between IVUS vs non IVUS guided primary angioplasty groups.

Secondary objectives:

To assess frequency of direct stenting in IVUS vs non IVUS guided primary angioplasty groups.

To assess frequency of post dilatation of stent in IVUS vs non IVUS guided primary angioplasty groups.

To assess frequency of slow flow /no reflow in IVUS vs non IVUS guided primary angioplasty groups.

To assess relation of baseline TIMI flow on the final TIMI flow in IVUS vs non IVUS guided primary angioplasty groups

4. Justification for study (whether of national significance with rationale): Though data is available regarding use of IVUS in PCI in general , targeted data in field of primary PCI is limited. Studies to evaluate the long-term impact of IVUS â€“guided PCI in patients with acute myocardial infarction have been done. However, the impact of intravascular ultrasound (IVUS)- guided PCI in final procedural TIMI flow and TMPG is uncertain. This study aims to understand the impact of IVUS on final TIMI flow and TMPG.

5. Departments involved:

Department of Cardiology, Kasturba hospital, Manipal

6. Study period: 1 year 6 months ; from 2023 (after acceptance of the study) to July 2025 .

7. Sample size:

Formula

Sample size was estimated by using nMaster software Version 2.0 by applying following details in the above formula. Based on the study â€œBeneficial effect of ticagrelor on microvascular perfusion in patients with ST-segment elevation myocardial infarction undergoing a primary percutaneous coronary interventionâ€ by Xuechao Wang and group [Coronary Artery Disease 2019, Vol 30 No 5 - DOI: 10.1097/MCA.0000000000000707]. Lower corrected thrombolysis in myocardial infarction frame count (19.68 Â± 7.38 vs. 22.35 Â± 8.30, P = 0.004).). Based on the above parameter with an alpha of 0.05 (2 sided) and power of 80% the estimated sample size using the sample size formula for two means comparison. The above parameter and formula give us a sample size of 133 samples per group. [8]

8. Materials and methods:

a) Inclusion and exclusion criteria:

Inclusion criteria:

a) All patients > 18 years and less than 80 years with STEMI undergoing primary angioplasty regardless of baseline TIMI flow.

Exclusion criteria:

a) Post- CABG patients

b) Those who received thrombolytic therapy or platelet glycoprotein IIb/IIIa receptor inhibitors prior to angiography.

c) Inability to cross lesion with IVUS catheter.

d) Pregnant

b) Biological materials required (type - blood, tissue etc and quantity): No

As IVUS provides ultrasound images of the coronaries , no biological samples are required. However , any relevant reports of blood tests already performed and are available with the patient will be collected.

c) Statistical methods: All the demographic variables will be presented using descriptive statistics i.e normally distributed variables by the mean and standard deviation (SD) and skewed variables by the median and interquartile range (IQR).Categorical variables will be presented using frequency and percentages. The statistical software SPSS 22.0 will be used for the analysis of the data.P < 0.05 will be considered as statistically significant .For TMPG and TIMI flow , Chi square test will be used. For corrected TFC , independent t test will be used. For Sample size , mean difference between the groups with respect to corrected TFC will be used.

d) Tools used:

1. BOSTON SCIENTIFIC â€“ iLAB POLARIS

2. PHILIPS- INTRASIGHT

Both these IVUS machines are available in Department of Cardiology (cardiac catheterization laboratory )

9. Detailed description of procedure / processes:

At the outset , we will obtain necessary approvals , including IRC (Institutional Review Committee) , IEC (Institutional Ethics Committee) approval and registration with CTRI (Clinical Trials Registry â€“ India) . Patients diagnosed with STEMI undergoing primary angioplasty will be recruited. Eligible patients will be explained in detail about the study and written informed consent will be obtained.The cases who fulfill the inclusion criteria will be studied.

We will collect baseline clinical data including electrocardiograms (ECG), echocardiograms (ECHO) and relevant laboratory values. The non IVUS group will have patients who undergo primary angioplasty without IVUS guidance. This is an observational case-control study in which data will be collected from the patients at baseline and after primary angioplasty with regard to TIMI flow and TMPG. Prior to procedure, aspirin, ticagrelor or clopidogrel will be given to patients in recommended doses. Primary PCI will be done according to standard techniques. Implantation of a stent(s) to cover the culprit lesion will be routinely implied unless infarct related artery was heavily calcified / tortuous precluding stenting. Drug-eluting stents (DES) will be used in all cases. In IVUS users, stent will be sized 1-1 to distal vessel reference area. Post dilatation would be done with proximal vessel area reference balloon at 16-18 atm only in case where expansion criteria not met. In IVUS group, direct stenting will be encouraged if lesion is not calcific. Post dilatation will be encouraged if stent expansion is < 85 %. TIMI flow before and after procedure along with TMPG and corrected TIMI frame count (CTFC) will be assessed. Steps carried out in primary PCI viz a viz predilatation /direct stenting and post dilation would be charted.

10. Outcome measures:

TIMI flow, TFC , TMPG between IVUS and non IVUS guided primary angioplasty groups.

11.Potential risks and benefits:

Risk : The risks associated with this study are minimal , given that it is solely observational in nature.

Benefits: This study holds the potential to yield valuable data on the impact of IVUS on final TIMI flow and TMPG in those with with STEMI undergoing primary angioplasty .

12.Ethical considerations and methods to address issues:

IEC approval will be obtained . Informed consent will be taken from the study participants. Confidentiality will be maintained. There are no additional tests, costs or visits for the patients for the purpose of this study.

A. Kim Y, Bae S, Johnson TW, Son NH, Sim DS, Hong YJ, Kim SW, Cho DK, Kim JS, Kim BK, Choi D, Hong MK, Jang Y, Jeong MH; KAMIRâ€NIH (Korea Acute Myocardial Infarction Registryâ€National Institutes of Health) Investigators [Link]. Role of Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Optimizing Outcomes in Acute Myocardial Infarction. J Am Heart Assoc. 2022 Mar;11(5):e023481. doi: 10.1161/JAHA.121.023481. Epub 2022 Feb 18. PMID: 35179041; PMCID: PMC9075077.

Objectives : To evaluate the long-term impact of IVUS-guided second-generation DES implantation inpatients with AMI.

Findings : Among study population , 1887 patients (21.0%) underwent IVUS-guidance, and 7120 patients (79.0%) underwent angiography-guidance for second-generation drug-eluting stent implantation. IVUS-guided PCI was associated with a significantly lower risk of target lesion failure at 3 years(4.8% versus 8.0%; hazard ratio [HR], 0.59; 95% CI, 0.47 to 0.73; P<0.001) compared with angiography-guided PCI. The difference was driven mainly by a lower risk of cardiac death and target vessel myocardial infarction.

Conclusion :In patients with acute myocardial infarction who underwent PCI with second-generation drug-eluting stent implantation, the use of IVUS guidance was associated with a significant reduction in 3-year target lesion failure, mainly driven by hard end points, such as cardiac death and target vessel myocardial infarction [ 6].

B. Andell P, Karlsson S, Mohammad MA, GÃ¶tberg M, James S, Jensen J, FrÃ¶bert O, AngerÃ¥s O, Nilsson J, Omerovic E, Lagerqvist B, Persson J, Koul S, Erlinge D. Intravascular Ultrasound Guidance Is Associated With Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared With Angiography Guidance Alone. Circ Cardiovasc Interv. 2017 May;10(5):e004813. doi: 10.1161/CIRCINTERVENTIONS.116.004813. PMID: 28487356.

Objectives : To study the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI .

Findings: IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50â€“0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47â€“0.82). In 340 propensity scoreâ€“matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37â€“0.80).

Conclusions: IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis.

C. Bae JH, Kwon TG, Hyun DW, Rihal CS, Lerman A. Predictors of slow flow during primary percutaneous coronary intervention: an intravascular ultrasound-virtual histology study. Heart. 2008 Dec;94(12):1559-64. doi: 10.1136/hrt.2007.135822. Epub 2008 Apr 1. PMID: 18381376.

Objectives: To evaluate the characteristics of lesions predisposing to the slow /no-reflow phenomenon during primary PCI in patients with acute myocardial infarction.

Findings : Slow flow developed in 12 patients (eight males). Patients with slow flow were likely to be older (67.5 (13.8) years vs 56.2 (13.9) years, p = 0.015), had more cardiogenic shock , larger fibrofatty volume over the entire lesion length higher remodelling index (1.10 (0.17) vs 0.99 (0.16), p = 0.043),

larger plaque area (16.2 (5.4) mm2 vs 12.5 (4.9) ,p = 0.025), fibrous area (8.0 (3.3) mm2 vs 5.4 (3.0) mm2, p = 0.014) and fibrofatty area (2.7 (2.2) mm2 vs 1.3 (1.6)mm2, p = 0.016) at the minimal lumen site than those without slow flow (37 males).

Conclusion : This study suggests that slow flow may be dependent on the tissue characterisation (fibrofatty volume) of the underlying lesion at the time of the primary PCI for acute myocardial infarction.

D. Kumar R, Qayyum D, Ahmed I, Rai L, Mir A, Awan R, Naseer AB, Basit A, Sial JA, Saghir T, Qamar N, Karim M. Predilation Ballooning in High Thrombus Laden STEMIs: An Independent Predictor of Slow Flow/No-Reflow in Patients Undergoing Emergent Percutaneous Coronary Revascularization. J Interv Cardiol. 2023 Jan 6;2023:4012361. doi: 10.1155/2023/4012361. PMID: 36712997; PMCID: PMC9839408.

Prospective descriptive cross-sectional study included patients with a high thrombus burden (â‰¥4 grades) who underwent primary PCI.

Objectives : To assess the effect of predilation ballooning on the incidence of intra procedure

SF/NR during primary PCI in patients with a high thrombus burden (â‰¥4 grade).

Findings : A total of 765 patients with high thrombus burden undergoing primary PCI were included in this study.Predilation ballooning was conducted in 346 (45.2%) patients. The incidence ofintraprocedure SF/NR was signifcantly higher (41.3% vs. 27.4%; p < 0.001) in patients with predilation ballooning than in those without preballooning, respectively. The incidence of intraprocedure SF/NR also remained signifcantly higher for the predilation ballooning cohort with an incidence rate of 41.3% as against 30.1% (p 0.002) for the propensity-matched cohort of patients without predilation ballooning with a relative risk of 1.64 (95% CI: 1.20 to 2.24). Moreover, the in-hospital mortality rate remained higher but insignifcant, among patients with and without predilation ballooning (8.1% vs. 4.9%; p 0.090).

Conclusion : Predilation ballooning can be associated with an increased risk of incidence of intraprocedure SF/NR during primary PCI in patients with high thrombus burden [2].

1] Nakao Y, Inaba S, Kinoshita M, Sumimoto T, Saito M, Aono J, Inoue K, Ikeda S, Yamaguchi O. Usefulness of intravascular ultrasound assessment after development of the slow flow phenomenon during percutaneous coronary intervention. Coron Artery Dis. 2022 Jun 1;33(4):302-310. doi: 10.1097/MCA.0000000000001126. Epub 2022 Jan 17. PMID: 35044335.

2] Kumar R, Qayyum D, Ahmed I, Rai L, Mir A, Awan R, Naseer AB, Basit A, Sial JA, Saghir T, Qamar N, Karim M. Predilation Ballooning in High Thrombus Laden STEMIs: An Independent Predictor of Slow Flow/No-Reflow in Patients Undergoing Emergent Percutaneous Coronary Revascularization. J Interv Cardiol. 2023 Jan 6;2023:4012361. doi: 10.1155/2023/4012361. PMID: 36712997; PMCID: PMC9839408.

3] Hong YJ, Ahn Y, Jeong MH. Role of Intravascular Ultrasound in Patients with Acute Myocardial Infarction. Korean Circ J. 2015 Jul;45(4):259-65. doi: 10.4070/kcj.2015.45.4.259. Epub 2015 Jul 16. PMID: 26240578; PMCID: PMC4521102.

4] van Gaal WJ, Banning AP. Percutaneous coronary intervention and the no-reflow phenomenon. Expert Rev Cardiovasc Ther. 2007 Jul;5(4):715-31. doi: 10.1586/14779072.5.4.715. PMID: 17605650.

5] Ghaffari S, Tajlil A, Aslanabadi N, Separham A, Sohrabi B, Saeidi G, Pourafkari L. Clinical and laboratory predictors of coronary slow flow in coronary angiography. Perfusion. 2017 Jan;32(1):13-19. doi: 10.1177/0267659116659918. Epub 2016 Jul 19. PMID: 27412375.

6] Kim Y, Bae S, Johnson TW, Son NH, Sim DS, Hong YJ, Kim SW, Cho DK, Kim JS, Kim BK, Choi D, Hong MK, Jang Y, Jeong MH; KAMIRâ€NIH (Korea Acute Myocardial Infarction Registryâ€National Institutes of Health) Investigators [Link]. Role of Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Optimizing Outcomes in Acute Myocardial Infarction. J Am Heart Assoc. 2022 Mar;11(5):e023481. doi: 10.1161/JAHA.121.023481. Epub 2022 Feb 18. PMID: 35179041; PMCID: PMC9075077.

7] Andell P, Karlsson S, Mohammad MA, GÃ¶tberg M, James S, Jensen J, FrÃ¶bert O, AngerÃ¥s O, Nilsson J, Omerovic E, Lagerqvist B, Persson J, Koul S, Erlinge D. Intravascular Ultrasound Guidance Is Associated With Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared With Angiography Guidance Alone. Circ Cardiovasc Interv. 2017 May;10(5):e004813. doi: 10.1161/CIRCINTERVENTIONS.116.004813. PMID: 28487356.

8] Shah GA, Malik T, Farooqi S, Ahmed S, Abid K. Frequency and impact of slow flow / no flow in primary percutaneous coronary intervention. J Pak Med Assoc. 2021 Nov;71(11):2548-2553. doi: 10.47391/JPMA.12-1390. PMID: 34783735.