Predictive model for left main coronary artery or triple vessel disease in patients with chronic coronary syndromes

This study used the retrospective data from patients with clinically suspicious CCS, aged 18 years or more, and scheduled for ICA. Patients were recruited at the Central Chest Institute of Thailand between January 2018 and December 2020. The exclusion criteria included patients with bundle branch block including right bundle branch block (RBBB), left bundle branch block (LBBB) or intraventricular conduction disturbances (IVCD), ventricular paced rhythm, moderate-to-severe valvular heart disease, stress cardiomyopathy, myocarditis, hypertrophic cardiomyopathy, hypertensive emergency, severe anemia (hemoglobin concentration <8 g/dL), myeloproliferative disorders, pericarditis, Brugada syndrome, or electrolyte abnormalities (hypokalemia, hyperkalemia, hypomagnesemia, hypocalcemia).

The baseline demographic data, 12-lead electrocardiography (ECG), and angiographic data were collected from the medical records. Predictors such as age, estimated glomerular filtration rate (eGFR), new onset of HF or left ventricular systolic dysfunction (LVSD) and suspected CAD, number of leads having STD, summation of leads having STD, STE in aVR, STE in V₁, anterior STD, lateral STD, and inferior STD were obtained and analyzed.

STD and STE were defined as STD and STE ≥0.05 mV, respectively. Anterior STD was defined as STD ≥2 leads in lead V₁–V₄. Lateral STD was defined as STD ≥2 leads in lead I, aVL, V₅–V₆. Inferior STD was defined as STD ≥2 leads in lead II, III, aVF. The extent of STD or STE was measured from TP segments at 80 ms after J point in the resting 12-lead ECG.

The angiograms were classified as LMCAD (≥50% stenosis) or TVD (≥70% stenosis), and non-LMCAD/TVD disease.

This study complied with the Declaration of Helsinki, the International Conference on Harmonization for Good Clinical Practice Guidelines, and designed following the recommendations of the STROBE and TRIPOD statements [12, 13]. The study protocol was approved by the Human Research Ethics Committee of the Central Chest Institute of Thailand (certificate of approval no. 018/2564).

We recruited 162 patients with clinically suspicious CCS eligible by using sample size calculation with simple random sampling. The average age was 66.1 ± 11.5 years. About half of those patients were males. There were 75 patients in the non-LMCAD/TVD and 87 patients in the LMCAD/TVD groups. About half of those patients had diabetes mellitus and most patients had hypertension and dyslipidemia. The average left ventricular ejection fraction (LVEF) was 56.1 ± 16.3%. About one-third of those patients had STE in aVR or V₁. The baseline characteristics are shown in Table 1.

Predictors were analyzed by using the univariate analysis and illustrated that age, new onset of HF or LVSD and suspected CAD, number of leads having STD, summation of leads having STD, STE in aVR, STE in V₁, anterior STD, lateral STD, and inferior STD significantly increased the risk of LMCAD/TVD, while eGFR significantly decreased the risk of LMCAD/TVD (P < 0.05). After the multivariate analysis, 4 predictors were associated with an increased risk of LMCAD/TVD. Those predictors included new onset of HF or LVSD and suspected CAD, STE in aVR, STE in V₁, and lateral STD (P < 0.05) as shown in Table 2. Based on these 4 predictors, the prediction score was created to predict the risk of LMCAD/TVD in Table 3.

The cut-off value of the prediction score by using ROC curve analysis was 3.0. The sensitivity, specificity, PPV, and NPV were 71.26% (95% CI: 60.57%–80.46%), 86.67% (95% CI: 76.84%–93.42%), 86.11% (95% CI: 75.94%–93.13%), 72.22% (95% CI: 61.78%–81.15%), respectively, with an AUC of 0.855 (95% CI: 0.796–0.914). The ROC curve is shown in Figure 1.

Figure 1.

ROC curve of the prediction score. ROC, receiver operating characteristic.

To date, previous studies have shown that ACS patients with LMCAD and TVD have been associated with several ECG changes such as STE in aVR, number and location of leads, extent of STD, and CV risk factors. However, there have been no data in patients with CCS undergoing ICA. This study showed that these patients with LMCAD and TVD undergoing ICA were significantly related to new onset of HF or LVSD and suspected CAD, STE in V₁ or aVR, and lateral STD.

A previous study showed that HF was the predictor of LMCAD/TVD in patients with ACS (OR: 32.50) [11]. In addition, this study showed that there was a statistically significant association between HF and LMCAD/TVD in patients with CCS (OR: 3.04) as well. Although HF in this study included LVSD from suspected CAD, it had less association with LMCAD/TVD than HF in ACS trials. Based on current knowledge, patients with ACS have higher risk compared with those patients with CCS. This may be an explanation for the lower association with LMCAD/TVD in this study. Interestingly, STE in V₁ during stress test was a predictor of LMCAD/TVD (OR: 4.3) [11], while this study showed that STE in V₁ during resting ECG was associated with LMCAD/TVD in patients with CCS (OR: 3.21). Symptomatic patients with STE in V₁ during resting ECG may be high-risk patients in ACS settings as well as CCS patients.

Moreover, a previous study showed that ST-deviations in aVR can predict severity, infarction volume, and prognosis in patients with acute myocardial infarction (MI) [17]. In addition, the meta-analysis has demonstrated that patients with non-ST-elevation ACS and STE in aVR were significantly associated with LMCAD, and a higher extent of STE was a higher probability of LMCAD [8]. This study showed that STE in aVR was associated with LMCAD/TVD with statistical significance in CCS patients; so, STE in aVR can be used for predicting LMCAD in both patients with ACS and CCS.

A previous study in patients with ACS showed that anterior STD, lateral STD, and inferior STD were related to the likelihood of having LMCAD/TVD [10]. This study showed that only lateral STD was associated with LMCAD/TVD with statistical significance, while anterior STD and inferior STD increased the probability of having LMCAD/TVD without statistical significance. The wide 95% CI of patients with anterior or inferior STD due to the small number of patients considered may be the explanation for the non-statistically significant predictors of LMCAD/TVD in this study. Larger studies are required for identifying these patients in future.

The prediction score including new onset HF or LVSD and suspected CAD, STE in V₁, STE in aVR, and lateral STD was developed. The ROC curve showed a cut-off value of 3.0 with a specificity and sensitivity of 86.67% and 71.26%, respectively. The AUC was 0.855. This study was the first study showing the prediction score used in patients with CCS undergoing ICA. This score can be used to select patients with high CV risk for ICA in future.

However, this study has several limitations. First, patients in this trial were studied in a tertiary hospital, and all patients were scheduled for ICA, indicating a higher CV risk and more severe CAD. This outcome might not be applied in the lower CV risk patients with CCS. Second, this is a retrospective chart review of patients having suspected CCS. Hence, some ACS patients might have been confused with more severe CCS patients. However, the findings in the coronary angiograms can be used for differentiating the CCS from the ACS settings. Finally, this study had a small patient number and selection bias cannot be excluded. Nevertheless, the prediction score can predict the probability of LMCAD/TVD in CCS patients with acceptable sensitivity and specificity.

The CCS patients with new onset of HF or LVSD and suspected CAD, STE in aVR, STE in V₁ and lateral STD were associated with an increased risk of LMCAD/TVD. The novel prediction score described here can predict LMCAD/TVD in those patients with acceptable sensitivity, specificity, PPV, and NPV.