Introduction
Approximately one-third of patients have moderate to severe calcified coronary lesions on coronary angiography. One study in 2014 included 6855 patients has indicated an incidence of moderate or severe coronary calcification of 32%, 5.9% of which comprised severe calcification [1–3]. Coronary calcification significantly increases the difficulty of coronary intervention and leads to poor prognosis. Coronary rotational atherectomy (RA) is the most effective method for treating severely calcified lesions. The specific indications for coronary RA include ostial lesions, unprotected left main coronary artery stenosis, chronic total occlusions, stent ablation, and angulated lesions (>45°) [4, 5]. The frequency of coronary RA for specific indications is greater than that of on-label use of RA in clinical practice. The incidence of in-hospital complications has been reported to be significantly greater in patients receiving RA for specific indications rather than on-label use [6]. However, the long-term clinical outcomes of RA for specific indications remain unknown. The purpose of the present study was to compare the long-term clinical outcomes of RA use for specific indications versus on-label use.
Methods
Study Design and Population
This single-center cohort study included all patients who received RA before stenting because of severe coronary calcification from July 2015 to December 2020 at Peking University People’s Hospital, China. Specific indications for coronary RA were defined as ostial lesions (right coronary or left main coronary artery), unprotected left main artery stenosis, chronic total occlusion, stent ablation, angulated lesions (>45°), and cardiac dysfunction (left ventricular ejection fraction <40%). Patients with one or more of the above characteristics were included in the specific indication group, whereas patients with none of the above characteristics were included in the on-label group. The main exclusion criteria were cardiogenic shock, saphenous vein graft lesion, severe coronary dissection, angulated lesions (>90°), last remaining vessel, and acute ST-segment elevation myocardial infarction.
Follow-Up and Endpoint
Clinical follow-up was performed through clinical visits or structured telephone interviews with the patients every 6 months. The demographic and clinical characteristics of all patients were obtained from the electronic record system.
The primary endpoint was the incidence of major adverse cardiovascular and cerebral events (MACCE), defined as the composite endpoint of all-cause death, ischemia-driven target vessel target vessel revascularization (TVR), non-fatal myocardial infarction (MI), in-stent thrombus, and stroke.
This study was approved by the ethics committee of the Peking University People’s Hospital, and written informed consent was obtained from all patients before participation.
Definition of Indices
Left main coronary disease was defined as >50% stenosis of the left main coronary artery. Multivessel disease was defined as >70% stenosis in two or more major coronary arteries (left descending, left circumflex, and right coronary artery). Bailout RA was defined as RA after failure of balloon dilatation or stent delivery. Planned RA was defined as RA initially used as an elective strategy, without previous device failure. PCI-associated MI was defined according to the third universal definition of MI [7].
RA Details
Before the procedure, all patients received an oral loading dose of 300 mg of aspirin and 600 mg of clopidogrel. During the procedure, all patients received unfractionated heparin at a dose of 70–100 U/kg or bivalirudin, a direct thrombin inhibitor, to maintain an activated clotting time (ACT) >300 s. The choice of vascular access and burr size was at the operator’s discretion. RA was performed with a rotablator (Scimed, Boston Scientific, Maple Grove, MN, USA). The burr size was selected to reach a burr/vessel ratio of 0.5–0.6. The RA speed ranged between 140,000 and 180,000 rpm, and the ablation time was 15–20 s. During RA, a continuous intracoronary infusion of unfractionated heparin and nitroglycerin was administered.
Statistical Analysis
Statistical analysis was performed in Statistical Package for Social Sciences for Windows 18.0 (SPSS, Chicago, IL). Continuous variables are expressed as mean ± standard deviation, and categorical variables are presented as frequencies (%). Univariate comparisons between groups were performed with Pearson’s chi-squared test for categorical variables and Student’s t-test for continuous variables. The Kaplan–Meier method was used to analyze the cumulative incidence of clinical events during follow-up. Differences were considered statistically significant at P<0.05.
Results
Patients’ Baseline Characteristics
A total of 301 patients were included in this study between July 2015 and December 2020. The patients’ baseline characteristics are shown in Table 1. RA was performed for on-label indications in 176 patients in the on-label group. In the remaining 125 patients in the specific indication group, RA was performed for specific indications. Angulated lesions (>45°) were the most common specific indications, which were followed by cardiac dysfunction (Table 2). The clinical characteristics were comparable between groups, and most patients had multivessel disease. The proportions of femoral access, total stent length, procedural time, and fluoroscopy volume were higher in the specific indication group than the on-label group, owing to the complexity of the lesions in the former.
Baseline Characteristics of the Study Population.
| On-label group (n = 176) | Specific indication group (n = 125) | P value | |
|---|---|---|---|
| Male (n, %) | 104 (59.1) | 87 (69.6) | 0.062 |
| Age (years) | 70.0 ± 8.7 | 68.3 ± 9.1 | 0.102 |
| BMI (kg/m2) | 25.1 ± 3.3 | 25.1 ± 2.9 | 0.980 |
| systolic pressure (mmHg) | 132.7 ± 18.3 | 135.4 ± 17.6 | 0.197 |
| Heart rate (beat/minute) | 67.6 ± 9.3 | 68.9 ± 10.9 | 0.254 |
| Hypertension (n, %) | 127 (72.2) | 101 (90.8) | 0.085 |
| Diabetes mellitus (n, %) | 89 (50.6) | 73 (58.4) | 0.180 |
| Dyslipidemia (n, %) | 65 (36.9) | 48 (38.4) | 0.796 |
| Smoking (n, %) | 77 (43.8) | 65 (52.0) | 0.159 |
| CKD (≥stage 2) (n, %) | 19 (10.8) | 18 (14.4) | 0.350 |
| Prior PCI (n, %) | 37 (21.0) | 35 (28.0) | 0.163 |
| Prior CABG (n, %) | 6 (3.4) | 3 (2.4) | 0.614 |
| Clinical presentation | 0.741 | ||
| SCAD (n, %) | 41 (23.3) | 36 (28.8) | |
| ACS (n, %) | 135 (76.7) | 89 (71.2) | |
| LVEF (%) | 66.4 ± 8.1 | 62.5 ± 10.7 | 0.001 |
| LVEF <40% (n, %) | 0 | 19 (15.2) | <0.001 |
| Left main disease (n, %) | 34 (19.3) | 36 (28.8) | 0.055 |
| Multivessel disease (n, %) | 161 (91.5) | 121 (96.8) | 0.541 |
| Aspirin (n, %) | 174 (98.9) | 125 (100) | 0.816 |
| P2Y12 inhibitor (n, %) | 175 (100) | 122 (97.6) | 0.425 |
| Statins (n, %) | 171 (97.7) | 120 (96.0) | 0.621 |
| β blocker (n, %) | 130 (74.3) | 98 (78.4) | 0.344 |
| Vessel access (n, %) | 0.012 | ||
| Radial | 142 (81.1) | 85 (68.0) | |
| Femoral | 34 (18.9) | 40 (32.0) | |
| Target vessel (n, %) | 0.115 | ||
| LM | 0 | 12 (9.6) | |
| LAD | 129 (73.3) | 85 (68.0) | |
| LCX | 12 (6.8) | 7 (5.6) | |
| RCA | 35 (19.9) | 20 (16.0) | |
| ECMO/IABP | 1 (0.6) | 5 (4.0) | 0.134 |
| Burr/artery ratio | 0.53 ± 0.06 | 0.53 ± 0.05 | 0.759 |
| Final burr size (mm) (n, %) | 0.223 | ||
| 1.25 | 60 (34.1) | 56 (44.8) | |
| 1.5 | 105 (59.7) | 58 (46.4) | |
| 1.75 | 10 (5.7) | 11 (8.8) | |
| 2.0 | 1 (0.6) | 0 | |
| More than 1 burr (n, %) | 15 (8.5) | 7 (5.6) | 0.339 |
| RA time (n, %) | 0.078 | ||
| Planned RA | 137 (77.8) | 86 (68.8) | |
| Bailout RA | 39 (22.2) | 39 (31.2) | |
| Cutting/scoring balloon (n, %) | 12 (6.8) | 9 (7.2) | 0.667 |
| IVUS/OCT-guided (n, %) | 57 (32.4) | 38 (30.4) | 0.372 |
| Total stent length (mm) | 57.8 ± 21.6 | 64.9 ± 22.7 | 0.007 |
| Average stent diameter (mm) | 3.0 ± 1.5 | 3.1 ± 1.8 | 0.852 |
| Procedural time (min) | 86.4 ± 32.3 | 95.5 ± 35.4 | 0.022 |
| Contrast volume (mL) | 254.9 ± 90.0 | 275.0 ± 89.4 | 0.056 |
| Fluoroscopy volume (mGy) | 1279.4 ± 906.2 | 1627.7 ± 1227.6 | 0.006 |
| Procedural success (n, %) | 174 (98.9%) | 120 (96.0%) | 0.105 |
BMI: body mass index, CKD: chronic kidney disease, PCI: percutaneous coronary intervention, CABG: coronary artery bypass graft, SCAD: stable coronary artery disease, ACS: acute coronary syndrome, LM: left main, LAD: left descending artery, LCX: left circumflex artery, RCA: right coronary artery, ECMO: extracorporeal membrane oxygenation, IABP: intra-aortic balloon pump, RA: rotational atherectomy, IVUS: intravascular ultrasound, OCT: optical coherence tomography.
Procedural Complications
The incidence of complications was higher in the specific indication group than the on-label group (10.8% vs. 20.0%, P=0.018). The most common complication was coronary dissection (at least type C), which was followed by slow or no reflow (Table 3). One patient in the specific indication group underwent an emergency coronary artery bypass graft (CABG) because of coronary perforation and tamponade.
Comparison of Complications between Groups.
| On-label group (n = 176) | Specific indication group (n = 125) | P value | |
|---|---|---|---|
| Total complications (n, %) | 19 (10.8) | 25 (20.0) | 0.018 |
| Bradycardia (n) | 2 | 5 | 0.819 |
| Coronary dissection (at least type C) (n) | 8 | 10 | 0.006 |
| Slow/no reflow (n) | 6 | 6 | 0.545 |
| Coronary perforation (n) | 1 | 2 | 0.376 |
| Tamponade (n) | 1 | 1 | 0.808 |
| Burr entrapment (n) | 0 | 1 | 0.236 |
| Rota-wire fracture (n) | 1 | 0 | 0.400 |
CABG: coronary artery bypass graft.
In-Hospital Outcomes
In-hospital MACCE (consisting of all-cause death, PCI-associated MI, ischemia-driven TVR, in-stent thrombus, and stroke) were slightly higher in the specific indication group than the on-label group, but the difference was not statistically significant. The most common MACCE during hospitalization was PCI-associated MI (Table 4).
Comparison of In-Hospital Outcomes between Groups.
| On-label group (n = 176) | Specific indication group (n = 125) | P value | |
|---|---|---|---|
| MACCE (n, %) | 17 (9.7) | 16 (12.5) | 0.392 |
| Death (n) | 2 | 1 | 0.773 |
| PCI related MI (n) | 13 | 12 | 0.494 |
| TVR (n) | 1 | 2 | 0.376 |
| In-stent thrombus (n) | 1 | 0 | 0.400 |
| stroke (n) | 0 | 1 | 0.236 |
MACCE: major adverse cardiovascular and cerebral events, PCI: percutaneous coronary intervention, MI: myocardial infarction, TVR: target vessel revascularization.
Long-Term Outcomes
The median follow-up duration of the 301 patients was 35 (10–57) months. During follow-up, MACCE occurred in 46 patients (15.3%) (Table 5). The incidence of MACCE was much higher in the specific indication group (25.6%) than the on-label group (13.6%) (HR=1.857, P=0.034). The Kaplan–Meier curve for MACCE is shown in Figure 1.
Comparison of Long-Term Outcomes between Groups.
| On-label group (n = 176) | Specific indication group (n = 125) | P value | |
|---|---|---|---|
| MACCE | 24 (13.6) | 32 (25.6) | 0.034 |
| Death | 11 | 18 | 0.018 |
| Non-fatal MI | 2 | 3 | 0.394 |
| TVR | 8 | 4 | 0.558 |
| Stent thrombus | 1 | 4 | 0.079 |
| stroke (n) | 2 | 3 | 0.400 |
MACCE: major adverse cardiovascular and cerebral events, MI: myocardial infarction, TVR: target vessel revascularization.
Kaplan–Meier curves for MACCE.
Kaplan–Meier curves for MACCE between the specific indication and on-label groups. The P value was calculated with log-rank test. MACCE, major adverse cardiac and cerebral events; ST, stent thrombus; MI, myocardial infarction; TVR, target vessel revascularization.
Discussion
RA is the most effective treatment for severely calcified lesions. Because RA is frequently used for specific indications in clinical practice, avoiding use of RA for any specific indications is difficult [6]. However, RA for specific indications, such as ostial lesions, unprotected left main coronary artery stenosis, chronic total occlusions, stent ablation, angulated lesions (>45°), and cardiac dysfunction is technically difficult, and the associated long-term outcomes are not well known [8–13]. Our study indicated a higher incidence of complications with RA for specific indications than with on-label use of RA, and poor long-term clinical outcomes of RA for specific indications.
Diffuse long lesions (>25 mm) are very common in real-world clinical practice and require RA [14, 15]. The European expert consensus and Japan expert consensus documents for RA both consider diffuse long lesions as a specific indication for RA [4, 5]. However, a previous study has indicated that using RA for coronary lesions ≥25 mm in length does not affect short- and long-term outcomes, particularly in patients with second-generation drug eluting stents [15]. RA for diffuse long lesions (≥25 mm) thus appears to be as safe as on-label use of RA. Therefore, in our study, the specific indication group did not include diffuse, long lesions.
The most common specific indications were angulated lesions in our study, in contrast to some previous research [16]. The risk of complications, such as burr entrapment or coronary perforation, is greater in angulated lesions and should be considered [12]. Some experts have reported the utility of halfway RA for angulated lesions [12].
Our study indicated comparable in-hospital outcomes between groups; however, MACCE were higher in the specific indication group than the on-label group, possibly because of the higher proportion of left main lesions, chronic total occlusion and cardiac dysfunction in the specific indication group, all of which had poor long-term outcomes.
Our study has several limitations. First, this was a single-center observational study, in which selection bias was inevitable. Second, the distribution of specific indications was heterogeneous, and the numbers of cases of ostial lesions, chronic total occlusion, stent ablation, and left main coronary artery lesions were small.
Our study demonstrated that use of RA for specific indications was common in clinical practice and was associated with a higher incidence of complications and poor long-term clinical outcomes than on-label use of RA.