Secondary rotational atherectomy is associated with reduced occurrence of prolonged ST-segment elevation following ablation

We investigated 152 consecutive stable CAD patients with severely calcified lesions admitted to Kagoshima University Hospital for PCI between January 2018 and August 2022 in this retrospective cohort study. This study was approved by the Research and Ethics Committee of Kagoshima University Hospital and was carried out in accordance with the ethical principles stated in the 1975 Declaration of Helsinki. All patients provided written informed consent after admission, agreeing with the use of clinical test data for scientific research by the hospital.

Subjects comprised stable CAD patients with severely calcified lesions who underwent coronary angiography and successful PCI for clinical chest symptoms and/or myocardial ischemia, which was evaluated by fractional flow reserve or myocardial perfusion single-photon emission computed tomography. Inclusion criteria were as follows: 1) RA was required to debulk severely calcified lesions; and 2) intravascular ultrasound (IVUS) was performed. The exclusion criteria were as follows: 1) cases in which optical coherence tomography (OCT) or optical frequency domain imaging alone was used instead of IVUS; or 2) cases in which RA was performed after insertion of mechanical circulatory support. All patients were administered strong statin irrespective of dyslipidemia and dual-antiplatelet therapy (aspirin and thienopyridine: prasugrel or clopidogrel) before the procedure.

RA was performed using standard techniques, as previously described [12]. Initial rotational speed was set within the conventional range (180,000–200,000 rpm). Each run was performed with a slow pecking motion within 20 s, and excessive decreases in burr rotation speed (> 5000 rpm) were avoided as much as possible. We performed IVUS using a commercially available system (Altaview; Terumo, Tokyo, Japan) which automatically recorded at a pullback rate of 3 or 9 mm/s (30 or 10 frames/s). We assessed the grade of calcification in the target lesion by IVUS, and calcification with a calcium arch extending > 180° and calcium length > 5 mm in the target lesion was defined as moderate/severe calcification [13]. A primary RA strategy was defined as a procedure without antecedent balloon dilatation before RA (Fig. 1A–C) and secondary RA strategy was defined as a procedure with pre-dilatation using a small balloon (balloon/artery ratio ≤ 0.6 derived from IVUS measurement) (Fig. 1D–F). Primary or secondary RA strategy was performed on the basis of the operator’s judgement. In all cases, continuous intravenous infusion of nicorandil was started before the PCI procedure, and a drug cocktail (verapamil 5 mg, nitroglycerin 5 mg, heparin 10000 unit, and saline 500 ml) was infused into a targeted coronary artery through the RA catheter to prevent slow flow. Angiography was performed to confirm whether slow flow occurred immediately after RA in every case. Slow flow was defined as thrombolysis in myocardial infarction (TIMI) flow grade ≤ 2 without lesions leading to delayed filling of distal vessels. The burr-to-artery ratio was defined as the burr size divided by the reference diameter derived from IVUS measurements. In all cases, monitoring by 12-lead electrocardiography was performed during PCI and recorded at the end of PCI.

Laboratory values were obtained on admission before PCI. Left-ventricular ejection fraction (LVEF) was obtained from the official echocardiography report within 1 month before RA. Strong statins were defined as doses of atorvastatin ≥ 10 mg/day, rosuvastatin ≥ 2.5 mg/day, or pitavastatin ≥ 2 mg/day, based on PATROL trial showing the efficacy and safety of statin use in Japanese populations [14].

Clinical outcomes were retrospectively collected from our hospital records. Prolonged ST-segment elevation after RA was defined continued ST-segment elevation despite administration of intra-coronary vasodilators such as nitroprusside after the disappearance of slow-flow phenomenon without lesions leading to delayed filling of distal vessels. Peri-procedural myocardial infarction, including side-branch occlusion due to stenting, was defined as an elevation of creatinine kinase levels at least threefold above the normal upper limit within 48 h after PCI [1, 15].

Descriptive statistics are presented as frequency (percentage) for categorical variables and mean ± standard deviation or median and interquartile range (IQR) for continuous variables. Fisher’s exact test was used to compare the incidence of categorical variables, which were expressed as frequency and percentage. A logistic regression analysis was used to assess factors associated with prolonged ST-segment elevation after RA, reporting odds ratios (ORs) and 95% confidence intervals (CIs). Variables showing values of p < 0.05 on univariate analysis were entered into multivariate analysis. In addition, logistic regression modeling was performed to assess ORs for prolonged ST-segment elevation after RA. To evaluate the robustness of our results and assess the impact of confounding variables, we added the confounding variables to our model for each of the multiple pairs and compared the adjusted odds ratios. P values < 0.05 were considered statistically significant and all analyses were conducted using SAS software (JMP version 14.0).

The baseline clinical characteristics of patients are shown in Table 1. Median age was 71 years (IQR 66–80 years), and 108 patients (71%) were male. The primary RA strategy was applied in 56 patients (37%) and the secondary RA strategy in the remaining 96 patients (63%). In secondary RA strategy group, fasting plasma glucose level [median, 116 interquartile range (IQR) 97–160 mg/dL vs. 104 IQR 87–129, p = 0.031], using of drug-coated balloon (29% vs. 45%; p = 0.036), and 2-burr usage (21% vs. 36%; p = 0.038) were higher than those of primary RA strategy group. Age, diabetes mellitus, hemodialysis, LVEF, lesion length ≥ 20 mm, and burr size did not show significant differences between the primary RA strategy and secondary RA strategy groups.

Major complications induced by RA were not encountered in any cases (Table 2). Slow flow (final coronary angiography TIMI ≤ 2) was only seen in one case (2%), in a patient treated using the primary RA strategy. This case involved debulking by RA for in-stent restenosis with severe diffuse calcification. Prolonged ST-segment elevation following ablation was observed in ten cases (7%) in total, with patients treated using the primary RA strategy showing a higher incidence (13%) than patients treated using the secondary RA strategy (3%, p = 0.039).

Univariate logistic analysis was performed to investigate associations of baseline characteristics (including lesion characteristics and PCI procedure) with the occurrence of prolonged ST-segment elevation following ablation. In univariate analysis, levels of low-density lipoprotein cholesterol (LDL-C) (OR 0.95, 95% CI 0.93–0.99; p = 0.013), levels of triglyceride (OR 0.97, 95% CI 0.94–0.99; p = 0.040), and secondary RA strategy (OR 0.23, 95% CI 0.05–0.85; p = 0.028) were inversely associated with the occurrence of prolonged ST-segment elevation following RA (Table 3).

Multivariate logistic regression analysis modeling for the incidence of prolonged ST-segment elevation revealed that the secondary RA strategy was significantly associated with the occurrence of prolonged ST-segment elevation following ablation in all three models (Model 1: OR 0.24, 95% CI 0.05–0.95, p = 0.042; Model 2: OR 0.17, 95% CI 0.03–0.68, p = 0.018; Model 3: OR 0.21, 95% CI 0.03–0.87, p = 0.041) even after adjusting for relevant factors such as levels of LDL-C and triglyceride (Table 4). In addition, LDL-C (Model 1: OR 0.96, 95% CI 0.92–0.99, p = 0.020) and triglyceride (Model 2: OR 0.96, 95% CI 0.94–0.99, p = 0.025) correlated significantly with prolonged ST-segment elevation in Models 1 and 2. However, LDL-C and triglycerides did not reach the level of a significant independent association with prolonged ST-segment elevation in Model 3.

There are several limitations in the present study. First, this retrospective study of a single center involved a relatively small cohort of patients. Second, we did not analyze the IVUS parameters associated with lipid components that were recognized as factors in slow flow in this study. Third, there were a small number of cases with OCT-guided RA in the current study period, and the definition of severe calcification differs between OCT and IVUS. Furthermore, the burr-to-artery ratio was calculated using the reference diameter derived from IVUS. Therefore, the cases with OCT-guided RA were excluded in this study. Fourth, although all patients were administered a strong statin, the dose and specific agent were not standardized. Finally, as this study is retrospective, inherited limitations such as the potential for unmeasured confounding cannot be ruled out. Prospective clinical investigations of larger populations are necessary to clarify the effect of secondary RA strategy on the incidence of prolonged ST-segment elevation.