Long-Term Outcomes Following Percutaneous Coronary Intervention With Rotational Atherectomy for Severely Calcified Lesions

Abstract

Background

While severe calcification is associated with unfavorable clinical outcomes, rotational atherectomy (RA) has been used for lesion modification of severely calcified lesions. However, long-term outcomes after percutaneous coronary intervention (PCI) with RA have not yet been fully investigated.

Methods and Results

We enrolled 301 patients with 334 lesions, which were treated using PCI with RA. The primary outcome was target vessel failure (TVF) defined as a composite of cardiac death (CD), target vessel myocardial infarction (MI), and target vessel revascularization (TVR). The secondary outcome was a major adverse cardiac event (MACE), defined as a composite of CD, MI, TVR, and definite stent thrombosis (ST). In addition, the predictors of TVF were evaluated using Cox proportional hazards regression analysis. The mean follow-up duration was 36.6±27.0 months. The cumulative incidence rates of TVF were 20.6%, 29.1%, and 32.5% at 2, 4, and 6 years, respectively. The 6-year cumulative incidence of MACE was 32.9%. The independent predictors of TVF were hemodialysis (hazard ratio 3.22 [95% confidential interval 1.91–5.43]) and diabetes (2.10 [1.24–3.57]).

Conclusions

The 6-year TVF rate after RA reached over 30%. Hemodialysis and diabetes significantly impacted the long-term outcome. The strategy of PCI with RA should be carefully selected for severely calcified lesions in patients with hemodialysis and diabetes.

Long-term outcomes after percutaneous coronary intervention (PCI) for calcified lesions are unfavorable.¹ Even in the era of newer-generation drug-eluting stents (DES), moderately-to-severely calcified lesions are associated with worse clinical outcomes.² Lesion modification with rotational atherectomy (RA) before DES implantation is effective in improving short-term outcomes.³ The J2T registry, which evaluated long-term outcomes after RA, demonstrated that a high procedural success rate was obtained, but the long-term incidence of a major adverse cardiac event (MACE) was also high.⁴ However, as bare-metal stent and first-generation DES were used for more than half of the patients in the abovementioned study, there is a possibility that the study results do not reflect the current outcomes of PCI with newer-generation devices. Therefore, we investigated the long-term prognosis and its predictors after RA with the current PCI strategy.

Methods

Study Design and Patients

This study had a single-center, retrospective, and observational design. A total of 301 patients with 334 lesions, which were treated using PCI with RA between May 2015 and August 2022, were enrolled (Figure 1). Eligible patients were aged ≥18 years and considered good candidates for PCI by the heart team of cardiologists and surgeons at Kansai Rosai Hospital. The patients also had clinical evidence of ischemic heart disease and/or a positive functional study. Follow up was performed using a telephone interview, review of hospital records, or an outpatient visit. The study was conducted according to the ethical guidelines of the Declaration of Helsinki. The study protocol was approved by the Medical Ethics Committee of Kansai Rosai Hospital. Due to the retrospective nature of the study (observational research), written informed consent from patients was not required, in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan. Instead, relevant information regarding the study was made available to the public, and opportunities for individuals to refuse the inclusion of their data were ensured.

Figure 1.

Study flowchart. A total of 4,958 percutaneous coronary intervention (PCI) cases were performed for 7,069 lesions in Kasai Rosai Hospital between May 2015 and August 2022. Of these, 301 patients (334 lesions) who were treated using PCI with rotational atherectomy were enrolled and analyzed.

PCI Procedures

PCI procedures were performed according to standard practice. Elective patients received clopidogrel (75 mg/day) or prasugrel (3.75 mg/day) in addition to aspirin (100 mg/day) at least 1 week before PCI. For the emergent patients, the antiplatelet drugs (aspirin 200 mg and clopidogrel 300 mg or prasugrel 20 mg) were loaded before PCI. Intravenous heparin (5,000 IU) was administered immediately before the PCI procedure. The indications for RA were as follows:⁵ (1) lesions with an excessive amount of calcified plaque identified on imaging devices such as intravascular ultrasound (IVUS) or optical coherent tomography (OCT); (2) devices, such as a balloon catheter, imaging catheter, or stent, could not pass the lesion; and (3) residual indentation was identified, even when utilizing high-pressure balloon dilatation. After PCI, all patients received prasugrel (3.75 mg) or clopidogrel (75 mg) once daily in addition to aspirin (100 mg) for the optimal duration in accordance with the relevant guidelines.^6–8

Outcomes and Definitions

The primary outcome was target vessel failure (TVF), which was defined as a composite of cardiac death (CD), target vessel myocardial infarction (MI), and target vessel revascularization (TVR). Secondary outcomes included: (1) a MACE, which was defined as a composite of CD, MI, TVR, and definite stent thrombosis (ST); (2) all cause death; (3) CD; (4) MI; (5) TVR; (6) target lesion revascularization (TLR); (7) non-TVR; and (8) definite ST. CD was defined as any death resulting from an evident cardiac cause, any death related to PCI, an unwitnessed death, or death from unknown causes.⁹ MI was defined as Type 1, Type 3, or Type 4b based on the Third Universal Definition of Myocardial Infarction.¹⁰ TVR was defined as any repeat PCI or surgical bypass of any segment within the entire major coronary vessel that was proximal or distal to a target lesion, including upstream and downstream branches, and the target lesion itself.⁹ TLR was defined as any clinically indicated repeat PCI of the target lesion or bypass surgery of the target vessel performed for restenosis or another complication of the target lesion.⁹ Non-TVR was defined as any repeat PCI or surgical bypass of any segment of the non-target coronary artery.⁹ Revascularization was considered clinically indicated if follow-up angiography showed a percent diameter stenosis of ≥50% and if one of the following was present: a positive history of recurrent angina pectoris, presumably related to the target vessel, objective signs of ischemia at rest or during an exercise test, presumably related to the target vessel, and abnormal results of any invasive functional diagnostic test.⁹ Definite ST was defined according to the ARC definition.¹¹ Slow flow/no reflow was defined as Thrombolysis in Myocardial Infarction flow grade 0, 1, or 2 without mechanical obstruction on the angiogram immediately after RA.¹²

Statistical Analysis

Data are shown as mean and standard deviation (SD) for continuous variables or as percentages for discrete variables, unless otherwise indicated. Cumulative incidence rates were assessed using Kaplan-Meier analysis and compared between some groups using the log-rank test. A univariable Cox regression analysis was performed to determine the hazard ratio (HR). To identify the independent predictors of TVF, a multivariable analysis was then performed using a Cox proportional hazard model. Variables in the univariable analysis with P values <0.05 were selected for the multivariate analysis. The results of the model were presented as HRs and 95% confidence intervals (CIs). A 2-tailed P value of <0.05 was considered statistically significant. All analyses were performed using SPSS software version 29.0 (SPSS Inc. Chicago, IL, USA).

Results

Patient, Lesion, and Procedural Characteristics

Patient characteristics are shown in Table 1. The mean age was 74 years, and 74.4% were male. Hemodialysis and diabetes were present in 35.9% and 51.2% of patients, respectively. Table 2 shows the lesions and procedural characteristics. Approximately half of the lesions involved the left anterior descending artery, whereas bifurcation and chronic total occlusion lesions were present in 59.6% and 4.8%, respectively. Scoring or cutting balloons were used in 63.5% of the lesions. The most frequent maximum bur size was 1.5 mm. Slow flow or no reflow occurred in 11.1% of procedures. In terms of the final device, second-generation DES, drug-coated stent, and drug-coated balloon were used in 84.7%, 9.0%, and 6.3% of cases, respectively.

Table 1.

Patient Characteristics

	n=301
Female	77 (25.6)
Follow-up duration (months)	36.6±27.0
Age (years)	74±8.9
Body mass index (kg/m2)	23±4.5
Prior PCI	146 (48.5)
Prior CABG	17 (5.6)
Old myocardial infarction	42 (14.0)
Congestive heart failure	41 (13.6)
Stroke	11 (3.7)
Atrial fibrillation	36 (12.0)
Peripheral artery disease	74 (24.6)
Hemodialysis	108 (35.9)
Chronic kidney disease	133 (44.2)
Hypertension	219 (72.8)
Dyslipidemia	181 (60.1)
Diabetes	154 (51.2)
Hyperuricemia	34 (11.3)
Current smoking	60 (19.9)
HbA1c (%)	6.9±8.3
LDL-cholesterol (mg/dL)	91±33.4
eGFR	41.5±30.3

Data are presented as mean±SD, or n (%). CABG, coronary artery bypass grafting; eGFR, estimated glomerular filtration rate; HbA1c, hemoglobin A1c; LDL, low-density lipoprotein; PCI, percutaneous coronary intervention.

Table 2.

Lesion and Procedural Characteristics

	n=334
Diagnosis at the time of PCI
Acute coronary syndrome	38 (11.4)
Acute myocardial infarction	14 (4.2)
Unstable angina	24 (7.2)
Chronic coronary syndrome	296 (88.6)
Target vessel
Left anterior descending artery	197 (59.0)
Left circumflex artery	35 (10.5)
Right coronary artery	87 (26.0)
Left main trunk	15 (4.5)
Bifurcation	199 (59.6)
Chronic total occlusion	16 (4.8)
Maximum pre-dilatation balloon diameter (mm)	2.9±0.43
Maximum stent diameter (mm)	3.2±0.42
Total stent length (mm)	38.4±16.5
Pre-lesion length (mm)	38.4±19.7
Pre-diameter stenosis (%)	70.9±12.2
Post-diameter stenosis (%)	16.9±13.9
Scoring or cutting balloon	212 (63.5)
Maximum burr size (mm)
1.25	33 (9.9)
1.50	135 (40.4)
1.75	100 (29.9)
2.00	62 (18.6)
2.25	4 (1.2)
Slow flow/no reflow	37 (11.1)
Atrioventricular block during PCI	45 (13.5)
Troponin I after PCI (ng/mL)	0.94±3.32
CK after PCI (U/L)	221±342
CK-MB after PCI (ng/mL)	22.9±45.4
Type of stent
Second- and third-generation DES	283 (84.7)
DCS	30 (9.0)
DCB	21 (6.3)
Second- and third-generation DES+DCS	1 (0.3)
Imaging device
IVUS	237 (70.9)
OCT	74 (22.2)
IVUS+OCT	23 (6.9)

Data are presented as mean±SD, or n (%). CK, creatine kinase; DCB, drug-coated balloon; DCS, drug-coated stent; DES, drug-eluting stent; IVUS, intravascular ultrasound; OCT, optical coherence tomography; PCI, percutaneous coronary intervention.

Clinical Outcomes

Cumulative incidence rates of TVF were 20.6%, 29.1%, and 32.5% at 2, 4, and 6 years, respectively (Figure 2). The other outcomes are shown in Figure 3. Multivariate analysis demonstrated that hemodialysis and diabetes were independent predictors of TVF (Table 3). Additionally, we compared the cumulative incidence of TVF between large burr (1.75/2.0/2.25 mm) and small burr (1.25/1.50 mm), and it was similar between them (34.9±5.2% vs. 29.5±4.8%; P=0.83; Supplementary Figure).

Figure 2.

Cumulative incidence of target vessel failure (TVF). Cumulative incidence rates of TVF were 20.6%, 29.1%, and 32.5% at 2, 4, and 6 years, respectively. SE, standard error.

Figure 3.

Cumulative incidence rates of clinical outcomes. (A) Major adverse cardiac event. (B) All cause death. (C) Cardiac death. (D) Myocardial infarction. (E) Target vessel revascularization. (F) Target lesion revascularization. (G) Non-target vessel revascularization. (H) Definite stent thrombosis.

Table 3.

Predictors of Target Vessel Failure

	Univariate analysis			Multivariate analysis
	HR	95% CI	P value	HR	95% CI	P value
Age	0.983	0.959–1.007	0.160
Female	0.594	0.326–1.081	0.088
Body mass index	0.99	0.946–1.037	0.680
Old myocardial infarction	1.075	0.578–1.999	0.820
Congestive heart failure	1.556	0.852–2.843	0.151
Stroke	0.96	0.235–3.921	0.955
Atrial fibrillation	0.906	0.434–1.889	0.792
Peripheral artery disease	1.760	1.075–2.882	0.025	1.021	0.590–1.767	0.941
Hemodialysis	3.197	2.004–5.100	<0.001	3.222	1.912–5.429	<0.001
Chronic kidney disease	1.06	0.669–1.680	0.804
Hypertension	1.651	0.888–3.070	0.113
Dyslipidemia	0.734	0.458–1.176	0.199
Diabetes	1.927	1.184–3.137	0.008	2.100	1.236–3.570	0.006
Hyperuricemia	1.698	0.892–3.231	0.107
Current smoking	0.737	0.404–1.345	0.320
HbA1c	0.964	0.788–1.180	0.725
LDL-cholesterol	1.001	0.994–1.008	0.718
Target vessel (LAD reference)
LCX	2.426	1.222–4.817	0.011	1.843	0.893–3.804	0.098
RCA	2.314	1.391–3.851	0.001	0.983	0.441–2.187	0.966
LMT	1.216	0.219–5.084	0.789
Bifurcation	0.568	0.359–0.900	0.016	0.665	0.355–1.247	0.203
Chronic total occlusion	1.032	0.376–2.829	0.951
Maximum pre-balloon diameter	1.418	0.845–2.380	0.186
Maximum stent diameter	1.186	0.720–1.954	0.502
Total stent length	0.994	0.982–1.006	0.31
Pre-lesion length	0.99	0.978–1.002	0.115
Pre-diameter stenosis	0.995	0.977–1.014	0.632
Post-diameter stenosis	1.014	1.003–1.025	0.016	1.008	0.995–1.022	0.235
Scoring or cutting balloon	0.721	0.451–1.145	0.166
Maximum burr size (1.25 mm reference)
1.50 mm	3.013	0.923–9.843	0.068
1.75 mm	2.691	0.807–8.965	0.107
2.00 mm	2.843	0.823–9.826	0.099
2.25 mm	2.255	0.234–21.711	0.482
Slow flow/no reflow	0.751	0.344–1.640	0.473
AVB during PCI	1.855	1.047–3.284	0.034	1.968	0.911–4.255	0.085
ST change after PCI	0.763	0.330–1.765	0.527
Troponin I after PCI	1.004	0.946–1.065	0.893
CK after PCI (100 U/L increase)	0.997	0.900–1.105	0.96
CK-MB after PCI (100 U/L increase)	1.110	0.670–1.836	0.686
Type of finalized device (DES reference)
Drug-coated stent	1.193	0.570–2.497	0.640
Drug-coated balloon	1.44	0.576–3.605	0.435

AVB, atrioventricular block; CI, confidence interval; HR, hazard ratio; LAD, left anterior descending artery; LCX, left circumflex artery; LMT, left main trunk; PCI, percutaneous coronary intervention; RCA, right coronary artery.

Discussion

We evaluated long-term clinical outcomes after current PCI with RA for severely calcified lesions. The cumulative incidence of TVF was 32.5% at 6 years. The independent predictors of TVF were hemodialysis and diabetes.

Mid-Term Clinical Outcomes After PCI With RA

Liang et al. reported that the incidence of MACE (defined as a composite of all-cause mortality, MI, and TVR) after PCI with RA and DES was 17.8% at 1 year.³ In their report, first-generation paclitaxel-eluting stent (TAXUS, Boston Scientific, Natrick, MA, USA) was used in approximately half of the lesions. The Korea-ROCK Registry, which was performed from 2010 to 2019, showed that the cumulative 1.5-year incidence of TVF (defined as a composite of CD, target-vessel spontaneous MI, and TVR) was 16.0%, although the type of DES was unknown.¹³ In contrast, Hachinohe et al. reported that the 1-year TVF rate after PCI with RA and newer-generation DES from January 2013 to November 2015 was 6.6%.⁵ Our investigation demonstrated that the 1- and 2-year TVF rates were 14.0% and 20.6%, respectively, which were similar to the former 2 studies, but higher than that of Hachinohe et al. The indications of RA in Hachinohe et al.⁵ included fibrotic plaque in addition to calcified plaque, which might improve the outcome. In Kansai Rosai Hospital, we perform RA for lesions with severe calcification but not for those with fibrotic plaque.

Long-Term Clinical Outcomes After PCI With RA

The J2T Multicenter Registry, which investigated patients treated using PCI with RA from 2004 to 2015 in Japan, revealed that the 5-year cumulative incidence rates of MACE (a composite of all-cause death, acute coronary syndrome, ST, TVR, and stroke) and TLR were 46.7% and 17.7%, respectively.⁴ These results were similar to our results. While the usage rates of bare-metal stent and first-generation DES were 11.2% and 52.5%, respectively, in the J2T registry, our study included only second-generation DES or latter devices. However, the clinical outcomes were similar. Further improvements in device and technique are necessary to improve the clinical outcomes.

Predictors for TVF

Hemodialysis and diabetes were independent predictors for worse outcomes in the present study, while hemodialysis was the strongest predictor in the J2T registry.⁴ Matsuhiro et al. revealed that the lesions of patients with hemodialysis frequently included calcified nodules and it was a predictor of TLR in patients with hemodialysis.¹⁴ Early restenosis can occur in a lesion with calcified nodules,¹⁵ and the nodule protrudes to the lumen from between struts.¹⁶ Therefore, in the present study, patients with hemodialysis could often have a calcified nodule, which would impact on a worse clinical outcome. The optimal treatment for calcified nodules has not been established, and its development is mandatory to improve the clinical outcomes of patients with hemodialysis.

There are several reports regarding the relationship between diabetes and patient/lesion status. Kurihara et al. revealed that the number of yellow plaques and maximum yellow grade were higher in prediabetic patients than in non-diabetic patients, which reflected coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic patients.¹⁷ Diabetic patients have more diffuse coronary artery lesions than non-diabetic patients.^18,19 In addition, thrombogenicity is higher in patients with diabetes than those with non-diabetes.^20,21 In terms of the post-PCI status, an angioscopic study demonstrated that arterial healing was delayed in patients with diabetes than those without diabetes 3–5 months after DES implantation.²² Kuroda et al. also reported that large glucose fluctuations were an independent risk factor for impaired uniform vessel healing after second-generation DES evaluated using OCT.²³ These factors would be the mechanisms of the relationship between diabetes and a worse clinical outcome after PCI with RA in the present study.

Clinical Implication

As diabetes and hemodialysis were independent predictors for poor clinical outcomes, PCI as a treatment strategy should be carefully selected for these patients, and coronary artery bypass grafting should be preferred. However, it is often difficult to undergo coronary artery bypass grafting due to patient’s poor clinical condition, and we cannot avoid performing PCI. In such situations, orbital atherectomy and intravascular lithotripsy in addition to RA may improve the clinical outcome. Although the algorithm is suggested for calcified lesions, there is no definite standard.²⁴ Further investigation is necessary to determine which devices are appropriate for which cases.

Study Limitations

This study has several limitations. First, this study had a single-center, retrospective design. A single-center fashion impacts on the difficulty of generalization given the different indications of atherectomy, procedures, burr size, or intracoronary imaging techniques among hospitals. However, the sample size and follow-up duration would be enough to elucidate the issue. Second, intravascular imaging data were not available, although the type of calcification would influence the results. Last, it would be worth demonstrating bleeding endpoints; however, we have no data on bleeding events. Further investigations are necessary.

Conclusions

The 6-year TVF rate after RA reached over 30%, and the presence of hemodialysis and diabetes significantly impacted the long-term outcome. The use of PCI with RA should be carefully selected for severely calcified lesions in patients with hemodialysis and diabetes. Further improvements in PCI devices and strategies are necessary.

Disclosures

T.I. has received lecture fees from Kaneka and Nipro. T.M. has received a research grant from Abbott Medical Japan.

IRB Information

Medical Ethics Committee of Kansai Rosai Hospital (reference no. 15D081g).

Supplementary Files

Supplementary File 1

Supplementary Figure. Cumulative incidence of Target Vessel Failure (TVF) Between Large Burr and Small Burr.

Data Availability

The study data will not be made available to other researchers for purposes of reproducing the results because of institutional review board restrictions.