CatLet© score for estimation of benefits of percutaneous coronary intervention versus optimal medical therapy in patients with acute myocardial infarction

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CatLet© score for estimation of benefits of percutaneous coronary intervention versus optimal medical therapy in patients with acute myocardial infarction

https://doi.org/10.21203/rs.3.rs-4842483/v1

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Background

The recently developed the Coronary Artery Tree description and Lesion EvaluaTion (CatLet©) angiographic scoring system has adequately accounted for the variability in coronary anatomy and considered both the severity of a coronary artery stenosis and its subtended myocardial territory. This study aims to investigate its potential roles played in guiding treatment strategies.

Methods

A total of consecutive 544 acute myocardial infarction (AMI) patients with single vessel disease were enrolled and their CatLet scores were calculated. The patients were divided into two groups: high (≥10) or low (< 10) CatLet score group. The primary endpoint was all-cause death. Cox regression survival analysis was performed to determine the benefits of percutaneous coronary intervention (PCI) versus optimal medical therapy in each group.

Results

The survival rate of all-cause death in the low CatLet score group was similar regardless of whether PCI was performed (P = 0.86). However, in the high CatLet score group, the survival rate was significantly higher when PCI was performed as compared to those whose PCI was not performed (P = 0.0067). The multivariable-adjusted hazard ratios (95% CI, P) were 0.20 (0.07–0.62, P = 0.005) for PCI in higher CatLet score group and 6.96 (0.22-205.65, P = 0.277) in lower CatLet score group.

Conclusions

The CatLet angiographic scoring system, capable to semi-quantify the myocardial territory, can be a useful tool to guide the treatment strategy for patients with AMI. Those with a CatLet score≥10 or more than five myocardial segments involved (CatLet score divided by the coefficient of 2) would benefit from the PCI strategy (http://www.chictr.org.cn; Registry Number: ChiCTR2000033730).

Health sciences/Cardiology/Cardiac device therapy

Health sciences/Cardiology/Cardiovascular biology

CatLet angiographic scoring system

percutaneous coronary intervention

acute myocardial infarction

For acute myocardial infarction (AMI), an infarcted territory is closely associated with cardiac function and clinical outcomes. Identification of the infarcted territory can be achieved via echocardiography, magnetic resonance imaging, emission computed tomography, and contrasted computed tomographic angiography[1–3]. However, these methods are largely cumbersome and hard to access in clinical practice. Most recently, we have developed the Coronary Artery Tree description and Lesion EvaluaTion (CatLet©) angiographic scoring system, in which we can obtain the myocardial territory subtended by a coronary artery according to the dynamic combinations of the left anterior descending artery, diagonal, and right coronary artery rather than the usually fixed distributions of coronary arteries as employed in the jeopardy score, Gensini score, and SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score[4–6]. The CatLet angiographic scoring system has thus provided 54 preset coronary circulation patterns to reflect coronary anatomy in its diversity and in its corresponding subtended myocardial territories [7, 8]. Our prior studies have demonstrated that the CatLet angiographic scoring system can be utilized to predict clinical outcomes for patients with AMI with a high reproducibility [9–12]. A head-to-head comparison study has even demonstrated that the CatLet angiographic scoring system is superior to the SYNTAX score with respect to outcome predictions for patients with AMI[10]. Given the derivation mechanisms of the CatLet angiographic scoring system and its performance in outcome predictions, we hypothesized that this novel angiographic scoring system can be used to guide treatment strategy for patients with AMI.

Patients

Consecutive patients with AMI, aged 18 years old or over, arriving later than 12 hours after symptom onset, were enrolled between January 1, 2012, and September 30, 2015. All of them had only major epicardial coronary artery disease. These patients were orally administrated with dual antiplatelet therapy, statins, angiotensin-converting enzyme inhibitor/angiotensin receptor blockade or beta-blockers. The percutaneous coronary intervention (PCI) was performed using the standard protocol. In this institution, immediate PCI (< 2 h) is usually performed for patients at very high risk. Patients at high risk usually underwent PCI within 24 h while those at intermediate or low risk usually underwent PCI within 72 h [13]. In our hospital, culprit lesions were usually treated in the index procedure while non-culprit lesions were usually treated in the staged procedure. The dual antiplatelet therapy lasted at least one year unless otherwise contraindicated, and the single antiplatelet therapy (aspirin or clopidogrel) maintained indefinitely. The exclusion criteria were as follows: (1) poor image quality; (2) coronary artery embolism; (3) abnormal coronary anatomy; (4) normal or < 50% diameter stenosis of CAG results; (5) multi-vessel disease and left main coronary artery disease; and (6) loss to follow-up.

Due to the retrospective nature of the study, written informed consent was waived by the Institutional Review Boards of Soochow University. This study complied with the Declaration of Helsinki regarding investigation in humans and was approved by the Institutional Review Board of Soochow University (No.2023(426)).

Data collection and definitions

The collected data included laboratory examinations, lifestyles, prior medical histories, and diseased coronary arteries. For patients with multiple hospitalizations, data from the first admission were collected, and for hospitalized patients with multiple laboratory examinations, data from the first examination were collected. Lifestyles considered were smoking and alcohol consumption. Current smokers were defined as those who smoked any tobacco in the previous 1 year or those who had quit within half a year. Past smokers were defined as those who had quit more than half a year earlier. Current alcohol consumers were defined as those who drank at least once a week in the previous 6 months. Past alcohol consumers were defined as those who had been abstinent in alcohol intake > 6 months earlier. Diagnosis of hypertension or type 2 diabetes mellitus has been according to acknowledged standards.

Lab examinations:

All patients underwent 8-hour fasting blood tests in the morning. Tests for albumin (Alb), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) (Lp(a)), and creatinine (Cr) were performed on Siemens 2400 bio-chemical analyzers following the manufacturer's specifications. Height and weight measurements were taken without shoes, with patients wearing light clothing. Body mass index (BMI) was calculated as body weight (in kilograms) divided by height (in meters) squared.

Scoring method:

The CatLet score system has been described in detail elsewhere [8, 10]. In brief, it is a novel scoring system that aims to adequately account for coronary variability and stratify the risk of patients with coronary artery disease. In the CatLet score system, the left anterior descending artery (LAD) and diagonal branches (Dx) were classified into three types, while the right coronary artery (RCA) was classified into six types. This resulted in a total of 54 (3×3×6) patterns of coronary circulation. Weighting factors were assigned to each coronary segment based on its subtended myocardial territory. Lesions with diameter stenosis greater than 50% in vessels larger than 1.5 mm were scored. For lesions with 50–99% diameter stenosis, a coefficient of 2.0 was assigned, while total occlusions were assigned a coefficient of 5.0. Non-occlusive lesions were scored directly, while in cases where the infarct-related artery was completely occluded, wiring or the use of a small balloon was employed to reveal the downstream lesion anatomy[14]. Persistently poor blood flow that prevented adequate visualization of the lesion was scored as a total occlusion. An individual lesion score is a product of the coefficient of the lesion and its weighting factor, and the total score is the sum of individual lesion scores. Thus, for a total occlusion lesion, three types of total score will produce: in total occlusion status, where coronary blood flow has been completely occluded revealed in the CAG exam; in partial occlusion status, where coronary blood flow has partially recovered after pretreatment with a small balloon; in “normal” status, where coronary blood flow has recovered to normal after PCI. For a non-occlusion lesion, two types of total score will produce: in partial occlusion status and “normal” status, where the definitions were the same as the aforementioned. In the current study, the CatLet score in partial occlusion status was used for final analysis. The CatLet score calculator is available at www.catletscore.com.

Endpoint, definitions, and follow-ups:

The primary endpoint of this study was all-cause death, defined as death from any cause. AMI was defined according to the third universal definition of myocardial infarction[15]. Follow-up was conducted through telephone interviews with living patients or their immediate relatives. Interviews were conducted until the date of death or the end of the study (September 2019), whichever came first. Medical records, discharge summaries, and angiographic data were systematically reviewed in case of adverse events. Death information was obtained from household registration management systems, hospitals, or their immediate relatives.

Statistical analysis:

The normality of continuous variables was assessed using the Shapiro-Wilk test, which indicated that all the variables did not conform to a normal distribution. Therefore, continuous variables were compared using the rank-sum test and expressed as median (interquartile range, IQR). Categorical variables were compared using the likelihood-ratio chi-squared test and expressed as frequencies (percentages). Multiple imputation methods (Chained equations, 10 times) were used to deal with the missing values. Event-free survival curves were generated using the Kaplan-Meier method, and survival between groups was compared using the Log rank trend test. Cox regression survival analysis was performed to examine the association of CatLet score with all-cause death. All statistical analyses were performed using Stata version 17.0. All P-values and confidence intervals were two-sided and a P value of < 0.05 was considered statistically significant.

Baseline characteristics of the study subjects

All subjects were divided into two groups based on their CatLet scores: CatLet≥10 and CatLet < 10. The total number of patients included in the study was 544, with 177 patients in the low score group and 367 patients in the high score group. The baseline data were largely comparable between both groups. Patients with the high CatLet score had significantly lower LVEF (P = 0.011). Diseased LADs were more frequently seen in both groups. Patients in the high CatLet score had an insignificant trend towards to be more likely to receive PCI procedure as compared with those in the low CatLet score (P = 0.052). Details can be found in Table 1.

Table 1

Baseline characteristics of study participants grouped by low (< 10) or high (≥10) CatLet score.
Factors		CatLet < 10	CatLet ≥ 10	P-Values
N		177	367
Male, n (%)		144(81.36)	294(80.10)	0.73
Age (IQR)		63(20)	64(19)	0.71
BMI, kg/m2		23.88(5.18)	24.09(3.98)	0.34
Smoking, n (%)				0.63
	Never	57(32.2)	133(36.2)
	Past	16(9.0)	29(7.9)
	Current	104(58.8)	205(55.9)
Drinking, n (%)				0.27
	Never	117(66.1)	266(72.5)
	Past	5(2.8)	11(3.0)
	Current	55(31.1)	90(24.5)
Hypertension, n (%)		107(60.5)	211(57.5)	0.51
Diabetes, n (%)		32(18.1)	72(19.6)	0.67
Albumin, g/L		39.30(4.90)	38.95(5.70)	0.29
TG, mmol/L		1.16(0.97)	1.28(0.91)	0.47
TC, mmol/L		3.99(1.32)	3.96(1.25)	0.62
Lp(a), mg/L		97(99.5)	104(199)	0.34
LDL-C, mmol/L		2.40(0.90)	2.47(0.94)	0.99
Creatinine, µmol/L		71(21.50)	71(23.20)	0.36
LVEF %		56(16)	53(18)	0.011
PCI, n (%)		162(91.5)	351(95.6)	0.052
Treated coronary lesion
	LAD, n (%)	87(49.2)	214(58.3)	0.044
	LCX, n (%)	40(22.6)	40(10.9)	< 0.001
	RCA, n (%)	35(19.8)	97(26.4)	0.090
All-cause death, n (%)		11(6.2)	31(8.4)	0.36
Notes: IQR, inter quartile range; TG, triglyceride; TC, total cholesterol; LP (a), lipoprotein(a); LDL-C, low-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; BMI, body mass index.; and PCI, percutaneous coronary intervention. LM, left main artery; LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery. Continuous variables were expressed as median (IQR); categorical variables were expressed as frequency and percentage.

CatLet score and its associations with 4-year all-cause death

In the low CatLet score, the survival rate of all-cause death was similar regardless of whether PCI was performed (P = 0.86). However, in the high CatLet score group, the survival rate was higher when PCI was performed as compared to those whose PCI was not performed (P = 0.0067) as shown in Fig. 1. When adjusting for age, sex, BMI, smoking, alcohol consumption, hypertension, diabetes, albumin, triglycerides, total cholesterol, serum creatinine, and LVEF, PCI reduced all-cause deaths by 66% (HR (95%CI), 0.34(0.13–0.94), P = 0.038). Regarding the PCI procedure, the multivariable-adjusted hazard ratios (95% CI) were 6.96 (0.22-205.65) for the low score group and 0.20(0.07–0.62) for the high score group (P = 0.005). These results suggest that AMI patients with a high CatLet score benefit from PCI. Further details can be found in Table 2 and Table S1.

Table 2

Multivariable-adjusted hazard ratios for PCI in patients with CatLet score less than versus greater than 10.
Treatment	CatLet < 10		CatLet ≥ 10
	HR (95%CI)	p Values	HR (95%CI)	p Values
§PCI	0.83(0.11–6.54)	0.865	0.26(0.09–0.74)	0.012
¶PCI	6.69(0.22-205.65)	0.277	0.20(0.07–0.62)	0.005
Notes: §PCI, denotes no adjustment of any risk factors; ¶PCI, adjusted for age, sex, body mass index, smoke, drinking, hypertension, diabetes, albumin, triglyceride, total cholesterol, creatinine, and left ventricular ejection fraction; HR (95%CI), hazard ratio (95% confidence interval).

To the best of our knowledge, this is the first study to validate that the CatLet score can be a useful tool to guide the treatment strategy for patients with AMI. The key findings of the current study include: (i) AMI patients with a higher CatLet score (≥ 10) can benefit from PCI; and (ii) there are no significant differences in survival rate in patients with a low CatLet score (< 10) receiving or not receiving PCI.

In univariate analysis, baseline characteristics were largely comparable between two groups except LVEF, where the lower LVEF was associated with the higher CatLet score. Competitive blood supply to left ventricle, 17-myocardial segmental model, and flow conservation formed the basis of the CatLet angiographic scoring system, which can be utilized to semi-quantify myocardial territory subtended by a coronary artery[7, 8]. The higher CatLet score indicated a broader myocardial territory in jeopardy. It thus makes sense that patients with higher CatLet score had a lower LVEF value.

Two or three-vessel disease interacted with each other and how these interactions had impacts on clinical outcomes were hard to be identified [17]. Therefore, in the current study, patients with one-vessel disease were enrolled and those with two or three-vessel diseases were excluded. Left main was also taken as multi-vessel disease and was thus excluded from this study.

In the current study, those with higher CatLet score benefited from PCI, but those with lower CatLet score did not. The CatLet score is the first of its kind that has explained the coronary anatomy in its diversity, graded the severity of a coronary lesion, and reflected the myocardial territory subtended by the diseased coronary artery. Thus, the key findings that those with higher CatLet score benefited from PCI, but those with lower CatLet score did not in the current study are wholly anticipated. The SYNTAX score, another anatomic angiographic scoring system, has been widely validated and used for stratification of patients with coronary artery diseases[18–22]. The SYNTAX score in part reflected the blood supply territory of the left heart subtended by a coronary artery although it is far from being adequate in this regard as compared to the CatLet score. It is also not surprising that patients with higher SYNTAX score will benefit from PCI and that patients with lower SYNTAX score will not[23, 24]. Of note, in patients with CatLet score < 10, stenting had a trend towards being a protective factor in the univariate analysis. However, stenting changed to be a hazard risk in multivariable analysis albeit also without statistical significances. This indicated that it may be hazardous to stenting an AMI patient with a low CatLet score, which are deserving of further study.

Limitations

There are several limitations to our study. First, it is a retrospective analysis, and the results should be considered as hypothesis-generating and need to be validated in randomized controlled trials. Second, a non-randomized controlled study is open to confounders, which may bias our findings. Third, our study only included AMI patients with one-vessel disease. Whether or not the key findings are replicated in the current study remains to be clarified. Lastly, sample size is moderate. A large sample-size study will be powered to elucidate the value of CatLet score in guiding the revascularization strategy.

The CatLet angiographic scoring system capable to semi-quantify the relative myocardial territory subtended by a coronary artery can be a useful tool to guide the revascularization strategy for patients with AMI. This finding warrants further investigation in the context of a prospective, randomized controlled trial.

Competing interests:

The authors declare no competing interests.

Funding:

This work was supported by the Sci-Tech Supporting Program of Jiangsu Commission of Health (M2021019) and the Medical Sci-Tech Innovation Program for Medical Care in Suzhou City (SKY2021005).

Author Contribution

HY wrote the main manuscript text, X-JP collected the data, PY and WP prepared the tables and figure and H-YM reviewed the manuscript.

Data Availability

Data is provided within supplementary information files.The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Takahashi, K. et al. investigators Pt: Redevelopment and validation of the syntax score ii to individualise decision making between percutaneous and surgical revascularisation in patients with complex coronary artery disease: Secondary analysis of the multicentre randomised controlled syntaxes trial with external cohort validation. Lancet. 396, 1399–1412 (2020).
Ahmed, N., Carrick, D., Layland, J., Oldroyd, K. G. & Berry, C. The role of cardiac magnetic resonance imaging (mri) in acute myocardial infarction (ami). Heart Lung Circulation. 22, 243–255 (2013).
Thomas, C. et al. Comparison of measurement of left ventricular ejection fraction by tc-99m sestamibi first-pass angiography with electron beam computed tomography in patients with anterior wall acute myocardial infarction. Am. J. Cardiol. 83, 1022–1026 (1999).
Di Serafino, L. et al. Myocardial mass affects diagnostic performance of non-hyperemic pressure-derived indexes in the assessment of coronary stenosis. Int. J. Cardiol. 370, 84–89 (2023).
Sotomi, Y. et al. Geographical difference of the interaction of sex with treatment strategy in patients with multivessel disease and left main disease: A meta-analysis from syntax (synergy between pci with taxus and cardiac surgery), precombat (bypass surgery versus angioplasty using sirolimus-eluting stent in patients with left main coronary artery disease), and best (bypass surgery and everolimus-eluting stent implantation in the treatment of patients with multivessel coronary artery disease) randomized controlled trials. Circ Cardiovasc Interv 2017;10.
Rampidis, G. P., Benetos, G., Benz, D. C., Giannopoulos, A. A. & Buechel, R. R. A guide for gensini score calculation. Atherosclerosis. 287, 181–183 (2019).
Xu, M. X. et al. written on behalf of the AMEICCG: The catlet score: A new coronary angiographic scoring tool accommodating the variable coronary anatomy for the first time. J. Thorac. Dis. 11, 5199–5209 (2019).
He, Y. M., Masuda, S. & Gao, C. Revisit of the catlet (hexu) angiographic scoring system: A narrative review. J. Thorac. Dis. 15, 2848–2858 (2023).
Liu, J. M. et al. Inter- and intra-observer variability for the assessment of coronary artery tree description and lesion evaluation (catlet(c)) angiographic scoring system in patients with acute myocardial infarction. Chin. Med. J. (Engl). 134, 425–430 (2020).
Xu, M. X. et al. The catlet score and outcome prediction in acute myocardial infarction for patients undergoing primary percutaneous intervention: A proof-of-concept study. Catheter Cardiovasc. Interv. 96, E220–E229 (2020).
Wang, H. et al. The predictive value of catlet(c) angiographic scoring system for long-term prognosis in patients with acute myocardial infarction presenting > 12 h after symptom onset. Front. Cardiovasc. Med. 9, 943229 (2022).
Xu, M. et al. Residual coronary artery tree description and lesion evaluation (catlet) score, clinical variables, and their associations with outcome predictions in patients with acute myocardial infarction. Chin. Med. J. (Engl). 10.1097/CM1099.0000000000002640 (2023).
Byrne, R. A. et al. 2023 esc guidelines for the management of acute coronary syndromes. Eur. Heart J. (2023).
Magro, M. et al. Value of the syntax score in patients treated by primary percutaneous coronary intervention for acute st-elevation myocardial infarction: The mi syntaxscore study. Am. Heart J. 161, 771–781 (2011).
Vojáček, J., Janský, P. & Janota, T. Third universal definition of myocardial infarction. Cor et Vasa. 55, e228–e235 (2013).
He, Y. et al. Association between serum uric acid and hypertension in a large cross-section study in a chinese population. J. Cardiovasc. Dev. Dis. ;9 (2022).
Yuan, D. et al. Real-world long-term outcomes based on three therapeutic strategies in very old patients with three-vessel disease. BMC Cardiovasc. Disord. ;21 (2021).
Kochar, A., Varshney, A. S. & Wang, D. E. Residual syntax score after revascularization in cardiogenic shock: When is complete complete? J. Am. Coll. Cardiol. 77, 156–158 (2021).
Cavalcante, R. et al. Impact of the syntax scores i and ii in patients with diabetes and multivessel coronary disease: A pooled analysis of patient level data from the syntax, precombat, and best trials. Eur. Heart J. 38, 1969–1977 (2017).
Farooq, V. et al. Quantification of incomplete revascularization and its association with five-year mortality in the synergy between percutaneous coronary intervention with taxus and cardiac surgery (syntax) trial validation of the residual syntax score. Circulation. 128, 141–151 (2013).
Genereux, P. et al. Quantification and impact of untreated coronary artery disease after percutaneous coronary intervention: The residual syntax (synergy between pci with taxus and cardiac surgery) score. J. Am. Coll. Cardiol. 59, 2165–2174 (2012).
Palmerini, T. et al. Prognostic value of the syntax score in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Analysis from the acuity (acute catheterization and urgent intervention triage strategy) trial. J. Am. Coll. Cardiol. 57, 2389–2397 (2011).
Ikeno, F. et al. Group B-DS: Syntax score and long-term outcomes: The bari-2d trial. J. Am. Coll. Cardiol. 69, 395–403 (2017).
Song, Y. et al. Impact of residual syntax score on clinical outcomes after incomplete revascularisation percutaneous coronary intervention: A large single-centre study. EuroIntervention. 13, 1185–1193 (2017).

No competing interests reported.

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You are reading this latest preprint version

CatLet© score for estimation of benefits of percutaneous coronary intervention versus optimal medical therapy in patients with acute myocardial infarction

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Introduction

Materials and Methods

Patients

Data collection and definitions

Lab examinations:

Scoring method:

Endpoint, definitions, and follow-ups:

Statistical analysis:

Results

Baseline characteristics of the study subjects

CatLet score and its associations with 4-year all-cause death

Discussion

Limitations

Conclusions

Declarations

Competing interests:

Funding:

Author Contribution

Data Availability

References

Additional Declarations

Supplementary Files

Status:

Version 1