European Journal of Cardiovascular Medicine

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality globally, with approximately 6% 1 of patients presenting with significant left main (LM) disease. Based on coronary artery dominance, the left main coronary artery (LMCA) provides blood to 75–100% of the myocardium2. The large myocardial area at risk in these cases makes left main coronary artery (LMCA) interventions particularly challenging, carrying a significant potential for major ischemic events. Recent randomized controlled trials (RCTs), registries, and meta-analyses have demonstrated that drug-eluting stent (DES) implantation in this high-risk population is both feasible and safe, offering outcomes comparable to coronary artery bypass grafting (CABG) in terms of major adverse cardiac and cerebrovascular events (MACCE).

While extensive multicentre data exist from Western and Far Eastern countries, there is a notable lack of real-world data on ULMCA PCI in the Indian subcontinent. The procedural success and long- term outcomes of ULMCA PCI are often influenced by the operator's experience, especially in this complex patient subset. Consequently, our study aims to bridge this gap by evaluating the procedural success and mid-term outcomes of ULMCA PCI with DES in a large cohort from a single centre in Central India over a five-year period. This study also aims to identify predictors of adverse outcomes, focusing on the comparative analysis of low versus high SYNTAX scores and the impact of imaging- guided versus non-imaging-guided interventions. The present study seeks to provide crucial insights into the comparative outcomes in this context and thereby contributing valuable data to the limited literature on ULMCA PCI in the Indian context.

This was a single-center, retrospective, observational study conducted at a tertiary care cardiology center in Central India. The study included all consecutive patients with unprotected left main coronary artery (ULMCA) disease who underwent percutaneous coronary intervention (PCI) using drug-eluting stents (DES) between January 2018 and 30 June 2023. Patients with incomplete data were excluded from the analysis.

The patient underwent percutaneous revascularization after a thorough discussion with the patient and their family, during which the heart team carefully considered the advantages and disadvantages of the procedure.

Ethics approval for this retrospective analysis was obtained from the Institutional Ethics Committee, and the study was conducted following the ethical principles of the Declaration of Helsinki, good clinical practice guidelines, and relevant local regulations.

Data for baseline clinical, angiographic, and procedural characteristics, as well as follow-up outcomes, were sourced from electronic medical records and telephonic follow up. A total of 252 patients were included, with follow-up periods ranging from a minimum of 1 year to 6.5 years. After excluding the lost to follow-up patients n=55 (i.e. 21.7%), the remaining 198 cases, were followed over a median follow-up of 753.5 days (IQR 25-75: 369 to 1573 days).

For statistical analysis, frequencies and proportions were reported for categorical variables, while measures of central tendency were used for continuous variables. The Chi-square test was applied for categorical data, and either a student t-test or Mann-Whitney U-test was used for continuous data based on distribution. A p-value of less than 0.05 was considered statistically significant. All analyses were performed using xxxxxxxxx.

DEFINITIONS AND ENDPOINTS:

Unprotected left main (ULM) stenosis was defined as stenosis of the left main coronary artery (LMCA) without prior coronary artery bypass grafting (CABG) or in the absence of patent grafts on angiography if previous CABG had been performed. Significant LMCA stenosis was identified as angiographic stenosis greater than 50%. Successful percutaneous coronary intervention (PCI) was defined as residual angiographic stenosis of less than 10% following stent placement, without significant side branch (SB) loss or flow-limiting dissection and TIMI 3 flow.

The complexity of the lesions was graded using the SYNTAX score. SYNTAX scores were calculated using the online SYNTAX score calculator, categorizing patients into low, intermediate, and high-risk groups.

Major adverse cardiovascular and cerebrovascular events (MACCE) included a composite of cardiac death, myocardial infarction (MI), and stroke, both during the hospital stay and follow-up. Cardiac death, MI, stroke were defined per the Academic Research Consortium-2 Consensus Document 3.

Use of Intracoronary imaging was left to the discretion of operator. When used it was recommended to assess procedural quality, with the following benchmarks:

• For IVUS: stented segment lumen cross-sectional area greater than 5.0 mm² or 90% of the distal reference lumen, plaque burden less than 50% within 5 mm of the stent edge, and no edge dissection longer than 3 mm involving the media.
• For OCT: proximal stent area greater than 90% of the proximal reference vessel’s minimum lumen area, distal stent area greater than 90% of the distal reference vessel’s minimum lumen area, complete stent apposition (distance from the vessel wall no more than 3.0 mm for a length longer than 3 mm), and no dissection that penetrates the media or exceeds a 90- degree arc.

The study included 253 patients undergoing left main PCI, with a mean age of 61.3 years, and a significant proportion (55.3%) were over 60 years old. Table 1 depicts baseline characteristics of cohort which was predominantly male (77.5%), and many patients presented with comorbidities, including hypertension (58.1%) and diabetes (41.1%). The majority of cases were classified as unstable angina (63.6%), with ST-elevation myocardial infarction (STEMI) occurring in 30.4% of patients.

Table 1: Baseline characteristics

Figure 1 provides a detailed representation of the distribution of cases over a six-year period, highlighting trends and variations in the number of cases managed annually.

Figure 1 - distribution of cases over a period of six years

The angiographic and procedural details are depicted in table 2, mean SYNTAX score was 17.8, indicating a predominance of lower complexity lesions, as 70.0% had a score below 22. Left ventricular ejection fraction (LVEF) averaged 49.5%. Most procedures involved stenting of the left main artery to the left anterior descending artery (78.7%), and drug-eluting stents (DES) were utilized exclusively in the cohort. Imaging guidance was employed in 30.4% of cases, primarily with intravascular ultrasound (IVUS)

Table 2: Angiographic and Procedural details

Figure 2 illustrates the year-wise distribution of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) usage over the study period. The data indicate a gradual increase in the utilization of both imaging modalities, with IVUS consistently being the preferred choice among practitioners. Notably, there was a marked rise in OCT usage in the later years, reflecting its growing acceptance in clinical practice. By the final year of the study, OCT use nearly doubled compared to its initial year, while IVUS maintained a steady but less pronounced increase.

Figure 2: Year wise distribution of IVUS and OCT

The results of your study reveal significant insights into patient outcomes following intervention. Out of the 198 patients followed for a median duration of 753.5 days, a composite outcome, which included cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke, was observed in 11.6% of cases (Figure 3). Among these outcomes, cardiovascular death was the most frequent, occurring in 8.6% of patients, while non-fatal MI was reported in 3.5%. Notably, there were no instances of non-fatal stroke during the follow-up period.

Figure 3 – Major adverse cardiac outcomes

The Kaplan-Meier (Figure 4) curve for overall survival indicates a gradual decline in survival probability over time among study participants undergoing left main PCI. Although there is a notable decrease, the survival rate remains relatively stable, suggesting a favorable long-term prognosis for this cohort.

Figure 4: Kaplan Meir curves for survival in study participants

The comparison of survival between Syntax score groups shown in Figure 5 reveals a log-rank test statistic of 4.390 with a p-value of 0.111, indicating no statistically significant difference in survival outcomes based on this scoring system.

Log rank test 4.390; p=0.111

Figure 5: Kaplan Meir curves for comparative survival in syntax score groups

The log-rank test for survival based on imaging data yields a statistic of 0.537 with a p-value of 0.464, suggesting that imaging modalities employed did not significantly impact survival outcomes (Figure 6).

Log rank test, 0.537. P=0.464

Figure 6: Kaplan Meir curves for comparative survival in imaging and non - imaging groups

The analysis of survival in patients with diabetes shows a log-rank test statistic of 2.611 and a p- value of 0.106, indicating a trend towards poorer survival, though not statistically significant(Figure - 7).

Log rank test 2.611; P=0.106

Figure 7: Kaplan Meir curves for comparative survival in diabetic v/s non – non-diabetic groups

Table 3: Predictor of Composite Outcomes

Age is significantly associated with composite outcomes, showing that older patients have a higher risk of adverse events. For each additional year, the odds of a composite outcome increase, emphasizing age as a critical risk factor in patients undergoing left main PCI.

Male sex does not significantly correlate with composite outcomes, with an unadjusted odds ratio of 0.79 (p=0.636), suggesting it may not be a relevant predictor. Further exploration into gender-specific outcomes could provide additional insights.

The Syntax score indicates a trend toward significance in predicting composite outcomes, with unadjusted odds ratios showing increased risk with higher scores, although the multivariate analysis yielded a p-value of 0.077, warranting further investigation.

Left ventricular ejection fraction (LVEF) shows no significant association with outcomes (odds ratio 0.98, p=0.224), raising questions about its utility as a standalone predictor.

Diabetes trends toward increased risk of adverse outcomes (odds ratio 2.15, p=0.089), suggesting a need for larger studies to fully assess its impact.

Hypertension is significantly associated with adverse outcomes, evidenced by an odds ratio of 3.91, underscoring the importance of managing this condition in PCI patients.

Overview Our study of left main coronary artery PCI in a single-center from Central India provides important real-world data on a procedure often reserved for high-risk patients. With a mean age of 61.3 years, a male predominance (77.5%), and a significant portion of the cohort presenting with unstable angina (63.6%) or STEMI (30.4%), this study highlights the clinical challenges in a resource- limited setting. These findings contribute to the global understanding of left main PCI, and offer a perspective from a region where access to advanced technology and immediate backup surgical options is limited.

The EXCEL trial 4 serves as a key reference for left main PCI, comparing its effectiveness to CABG. It established that PCI was non-inferior, showing a 5-year MACE rate of 15.4% in the PCI group. In our cohort, the MACE rate was slightly lower at 11.6%, with cardiovascular death being the most common event (8.6%). This may be attributed to the fact that most of our patients had low to intermediate complexity based on SYNTAX scores, along with some patient being lost to follow-up.

The NOBLE trial 5 concluded that CABG was superior to PCI, reporting a higher 5-year MACCE rate in the PCI group (28% vs. 18%). In contrast, our study showed a lower MACE rate, which could be due to differences in patient selection, less complex lesions based on SYNTAX scores, and variations in follow-up durations. While the NOBLE trial emphasized the need for repeat revascularization, this was less commonly seen in our cohort, potentially due to limited follow-up resources and geographic challenges in accessing repeat procedures.

The SYNTAX trial 6 categorized patients by lesion complexity, recommending CABG for those with high SYNTAX scores. In our study, the mean SYNTAX score was 17.8, with 70% of patients scoring below 22, classifying them as low to intermediate risk. These patients experienced favorable outcomes, aligning with the low to intermediate-risk groups in the SYNTAX trial. In SYNTAX, patients with low (0-22) and intermediate (23-32) scores treated with PCI had comparable outcomes to CABG

at 5 years, while those with higher scores (≥33) benefited more from surgery. Our cohort's outcomes reflect similar success to the low-intermediate groups in SYNTAX, supporting PCI's effectiveness in patients with less complex disease. However, in our study, we did not compare our PCI patients with CABG patients. Comparison with Real-World Data from India

Our findings align with other studies from India, such as G.Parale et al.'s work on left main PCI in resource limited settings, which underscores the challenges of performing complex interventions in resource-limited settings7. Similar to their study, we faced constraints related to imaging availability, lack of hybrid revascularization teams, and the need for rapid clinical decision-making based on angiography alone. Despite these limitations, our outcomes, particularly in terms of MACE and survival, are encouraging, suggesting that left main PCI can be performed successfully with adequate operator experience and careful case selection.

Our study is consistent with the findings of P.K. Goel 8 et all and Pratap Kumar 9 et al., which showed that PCI of the left main coronary artery is both feasible and effective, with favorable immediate and mid-term outcomes. Contrary to their finding in our cohort, the SYNTAX score did not have a significant influence on major adverse cardiovascular events (MACE); however, long-term follow-up is necessary to confirm this observation. This is likely due to the loss of many patients to follow-up and the small number of patients with high-complexity lesions, specifically those with a SYNTAX score above 32.

LIMITATIONS

Our study has several limitations that should be acknowledged. First, being a single-center study, its generalizability is limited. The lack of advanced imaging tools such as IVUS or OCT in a substantial number of cases may have affected the precision of lesion assessment and stent placement, potentially influencing outcomes. Furthermore, the relatively small sample size and observational design, along with the inherent selection biases typical of real-world registries, limit the strength of our conclusions. Additionally, our follow-up was short to mid-term, and the number of patients with highly complex lesions (SYNTAX score over 32) was very low, with most patients having lower SYNTAX scores, which likely contributed to the lower MACE rate compared to some trials.

artery (ULMCA) lesions and low to intermediate SYNTAX scores, PCI with drug-eluting stents (DES) by experienced operators is safe, demonstrating low rates of major adverse cardiac and cerebrovascular events (MACCE) at mid-term follow-up. SYNTAX scores, imaging guidance, and diabetes did not significantly influence outcomes. Age (>60 years) and hypertension emerged as significant predictors of adverse outcomes. Although SYNTAX score and diabetes exhibited trends toward increased risk, these were not statistically significant. Male sex and left ventricular ejection fraction (LVEF) showed no association with outcomes, indicating a need for further research

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