ROVUS Asia Registry (Evaluate Safety and Effectiveness of Rotational Atherectomy and Intravascular Ultrasound for Heavily Calcified Coronary Lesion)
Conditions: Coronary Artery Calcification
Sponsor: National Heart Centre Singapore

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Study Protocol 
Registry Name 
ROVUS (Evaluate Safety and Effectiveness of Rotational Atherectomy 
and Intravascular Ultrasound for Heavily Calcified Coronary Lesion) 
Asia Registry  
Version No.  
Version 3 
Date 
17th January 2021 
Sponsor 
National Heart Centre Singapore (NHCS) 
Boston Scientific Corporation  
Type of clinical trial 
Investigator-initiated 
Study hypothesis 
Rotational atherectomy with or without other calcium debulking 
therapies is a safe adjunctive procedure for patients with severe 
coronary calcification requiring PCI 
Study population 
All patients with signed informed consent for percutaneous coronary 
intervention (PCI) and are eligible for calcium debulking treatment with 
rotational atherectomy with or without other forms of calcium 
debulking therapies will be enrolled into this study 
Study aim 
1. To describe the use of RA in real world practice in Asia 
2. To determine predictors of procedural success 
3. To determine predictors of major procedural complications: 
perforation and no-reflow phenomenon 
4. To assess the clinical outcome of patients undergoing RA for 
heavily calcified coronary lesions. 
Study equipment 
1. ROTABLATORTM or ROTAPROTM (Rotational Atherectomy 
System) 
2. Opticross or Opticross HD (IVUS) - preferred 
3. SYNERGY or SYNERGY XD (DES) - preferred 
4. Other calcium debulking equipments used e.g. Orbital 
atherectomy, shockwave lithotripsy, laser, very high-pressure 
balloon, angiosculpt, cutting balloon etc 

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Final selection of imaging platform, type of stents, adjunctive calcium 
debulking strategies and use of pre-/post-dilation is left to operator’s 
discretion 
Device specification 
1. The 
ROTABLATORTM 
or 
ROTAPROTM 
(Rotational 
Atherectomy System) consist of hardware (console, high-
pressure gas tank and foot pedal) and disposable components 
(wire guide, burr head and advancer).  
2. The burr head sizes are 1.25mm,1.5mm,1.75mm, 2.0mm, 
2.25mm, 2.38mm, 2.5mm 
3. Other equipments used are subject to respective device 
specifications 
Study design 
Regional prospective, multicenter observational study 
Estimated sample size 1000 patients to be enrolled, with each site enrolling at least 65 to 120 
patients.  
Proposed study 
countries/ Sites 
1. Singapore: National Heart Centre Singapore, National 
University Hospital, Tan Tock Seng Hospital 
2. Japan: Kokura Memorial Hospital, Sapporo Cardiovascular 
Clinic, Sendai Kousei Hospital 
3. Malaysia: Serdang Hospital, Cardiac Vascular Sentral Kuala 
Lumpur 
4. Thailand: Central Chest, King Chulalongkorn 
5. Vietnam: Cho Ray Hospital, Bach Mai Hospital 
Patient selection 
Inclusion Criteria 
Subjects MUST fulfill ALL the following requirements in order to 
be eligible for the study:  
1. At least 21 years of age of any gender 
2. Able to understand and sign an informed consent form 
3. Presence of clinical indication for PCI and/or stent placement 
4. Subjects willing to comply with all research and follow-up 
requirements 
5. Angiographic criteria (ONE of the following criteria MUST be 
met) 

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a. Target lesions visually have at least moderate 
calcifications* 
b. Target lesion balloon dilatation failure 
c. Inability of devices (microcatheters, balloons, stents or 
imaging devices) to pass through the target lesion 
d. Intravascular imaging shows severe calcification* 
6. Procedural criteria 
a. All patients treated with RA with or without other forms 
of debulking therapy 
 
* Moderate calcification is defined as radio-opacities noted only during cardiac 
cycle prior to contrast injection whereas severe calcification is defined as radio-
opacities seen without cardiac motion prior to contrast injection, usually affecting 
both sides of the arterial lumen1 
Study duration 
2-year recruitment period with a minimum 1-year of clinical follow-up. 
Patients will be enrolled into the study at the point of treatment with 
rotational atherectomy 
Primary efficacy 
endpoint 
Procedural success defined as < 20% residual stenosis in treated 
segment without on-table mortality with TIMI 3 flow   
Primary safety 
endpoint 
All rotational atherectomy related complications 
Secondary study 
endpoints 
 
1. Death (in-hospital and at 1-year follow-up) 
2. Periprocedural myocardial infarction (MI) defined as either 
(within 48 hours of procedure) 
a. Peak CK-MB ≥ 10x ULN OR ≥ 5x ULN + new 
pathologic Q waves in ≥ 2 contiguous leads/ new 
persistent LBBB2 OR 
b. Peak Troponin T or I > 5x ULN + new pathologic Q 
waves/ ischemic ECG changes3 
3. Complications: Significant coronary perforation defined as 
(within 48 hours of procedure) 
a. At least Type II, III or III CS based on Ellis 
classification4 
4. Complication: no-reflow or slow flow (within 48 hours of 
procedure) 
5. Procedural time defined as  

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a. Time of guide engagement to removal of guide 
Follow-up 
All patients will be followed-up via telephone consultation at the 12-
month mark from index rotational atherectomy procedure 
Recommended 
management 
Pre-procedural antiplatelet regimen 
(i) 
Aspirin:  
a. If aspirin naïve, 300mg loading followed by 100mg OM 
b. If already on aspirin 100mg OM, ensure daily 
compliance for at least 72 hours prior to procedure 
AND 
(ii) 
Clopidogrel:  
a. If clopidogrel naïve: 600mg loading followed by 75mg 
OM 
b. If already on clopidogrel 75mg OM, ensure daily 
compliance for at least 1 week prior to procedure 
OR 
(iii) 
Ticagrelor:  
a. If ticagrelor naïve: 180mg loading followed by 90mg 
BD 
b. If already on ticagrelor 90mg BD, ensure daily 
compliance for at least 24 hours 
OR 
(iv) 
Prasugrel 
a. If prasugrel naïve: 60mg loading on table if planned for 
PCI followed by 10mg OM 
b. If already on prasugrel 10mg OM, ensure daily 
compliance for at least 24 hours 
Intracoronary medications 
The administration of intracoronary glyceryl trinitrate (GTN) is 
recommended prior to coronary angiography of both right and left 
coronary artery.  
 

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Use of any of the following intracoronary medications is left to operator 
discretion as per site practice and/ or product instructions  
(i) 
Calcium Channel blockers (CCB): Verapamil/ Diltiazem 
(ii) 
Adenosine 
(iii) 
Nitroprusside 
Anti-thrombotics 
Use of any of the following antithrombotic regimen is left to operator 
discretion as per site practice and/or product instructions  
(i) 
Heparin 
(ii) 
Bivalirudin 
(iii) 
Fondaparinux 
(iv) 
Group 2b/3a inhibitors e.g. eptifibatide 
(v) 
Cangrelor 
Pre-procedural preparation 
(i) 
For RCA/ dominant LCx lesions, operators can consider to 
standby atropine or temporary pacing wire (TPW) insertion 
if patient develops significant bradycardia/ cardiac 
conduction delays during the procedure 
Intracoronary imaging 
(i) 
The 
preferred 
intracoronary 
imaging 
platform 
is 
Intravascular Ultrasound (IVUS) i.e. Opticross or Opticross 
HD prior to intervention to evaluate target lesion 
characteristics and post-intervention to optimize stent 
expansion. However, the final selection is left to the 
discretion of the operators. 
(ii) 
Optical coherence tomography (OCT) is an alternative if 
deemed appropriate by the operators. 
Post-procedure 
(i) 
IV normal saline hydration based on clinical judgement to 
reduce risk of contrast induced nephropathy (CIN) 
(ii) 
If TPW was inserted but nil further brady-arrhythmia was 
noted, TPW can be safely removed prior to transfer out of 
cardiovascular laboratory 
(iii) 
To reduce post-procedural vasospasm, IV nitroglycerin can 
be administered 

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(iv) 
The subjects should receive dual antiplatelet therapy 
(DAPT) – one being that of aspirin and the other being a 
P2Y12 inhibitor – post- procedurally. The dose and duration 
of treatment is to be determined by the operator. 
(v) 
All patients are recommended to be on DAPT for at least 6 
months in duration post-PCI extendable to at least 12 
months if they are deemed at low risk for bleeding.  
Statistical analysis 
All analysis will be performed using SAS or STATA 
 
Analysis will be conducted in two approaches, (1) according to the 
intention-to-treat (ITT) principle and (2) per-protocol analysis. 
Sub-group analysis 
 
This study will evaluate real world clinical outcomes of all enrolled 
patients who have undergone calcium debulking therapies. The 
following sub-groups listed below (but are not limited to) may be used 
for further analysis:  
(i) 
Acute coronary syndrome 
(ii) 
Lesion length 
(iii) 
Bifurcation lesions 
(iv) 
Multiple overlapping stents (≥ 2 stents for each epicardial 
coronary artery) 
(v) 
Chronic kidney disease 
(vi) 
Multivessel disease (≥ 2 vessel CAD) 
(vii) 
Left main (LM) equivalent 
(viii) Chronic total occlusions (CTO) 
(ix) 
Severely impaired LVEF i.e. ≤ 30% 
(x) 
IVUS subgroup  
Primary site 
National Heart Centre Singapore (NHCS) 
 
 
 
 
 
 
 

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Study flow chart 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Data collection schedule 
 
Baseline 
Follow-up 
Time 
≤ 48h after 
PCI 
12m 
Visit timeline 
Vstart 
Vend 
Informed consent 
X 
 
Entry criteria 
X 
 
History / demographic data 
X 
 
Symptoms (CCS score) 
X 
X 
Laboratory^ 
X 
 
DAPT use data* 
 
X 
Adverse events recording 
X 
X 
Note: 
#  Laboratory testing: full blood count, liver function (ALT, AST), renal function (BUN, creatinine), lipids 
(total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides), glucose, coagulation panel (APTT/PT), 
myocardial injury markers include: CK, CK-MB, TnT / TnI.etc. 
 
* DAPT recommendations may differ based on clinical situation/ stent use. Data collected will be type of 
antiplatelets and recommended duration for each antiplatelets used.  
 
Note: All subjects will be followed up 12 months post PCI via telephone consult to check on symptoms, 
compliance, and development of adverse events. Medical records will also be reviewed at the end of 12 
months for any clinically significant events. 
 
 
 

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Table of Contents 
1. Research background ------------------------------------------------------------------------------------- 15 
1.1 Introduction to disease --------------------------------------------------------------------------------------------------------------------- 16 
1.1.1 
Disease Profile---------------------------------------------------------------------------------------------------------------- 16 
1.1.2 
Epidemiology and risk factors -------------------------------------------------------------------------------------------- 16 
1.1.3 
Pathophysiology and classification -------------------------------------------------------------------------------------- 16 
1.1.4 
Detection of CAC ------------------------------------------------------------------------------------------------------------ 16 
1.2 
Introduction to treatment -------------------------------------------------------------------------------------------------------------- 17 
1.2.1 
Rotational atherectomy ------------------------------------------------------------------------------------------------------------- 17 
1.3 
Introduction to equipment ------------------------------------------------------------------------------------------------------------- 17 
1.3.1 
Structure and basic principle of ROTABLATORTM ------------------------------------------------------------------------ 17 
1.3.2 
Principle ------------------------------------------------------------------------------------------------------------------------------- 19 
2. Study Aim -------------------------------------------------------------------------------------------------- 20 
3. Selection and exit criteria -------------------------------------------------------------------------------- 20 
3.1 Inclusion criteria ---------------------------------------------------------------------------------------------------------------------------- 20 
3.2 Exclusion criteria --------------------------------------------------------------------------------------------------------------------------- 21 
3.3 Exit criteria ----------------------------------------------------------------------------------------------------------------------------------- 21 
3.4 Early termination --------------------------------------------------------------------------------------------------------------------------- 21 
3.4.1 Study termination criteria ------------------------------------------------------------------------------------------------------- 21 
3.4.2 Study site termination criteria ------------------------------------------------------------------------------------------------- 22 
4. Study design ------------------------------------------------------------------------------------------------ 22 
4.1 Research design ----------------------------------------------------------------------------------------------------------------------------- 22 
4.2 Study stages ---------------------------------------------------------------------------------------------------------------------------------- 23 
4.2.1 Index visit: Within 48 hours of PCI ------------------------------------------------------------------------------------------- 23 

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4.2.2 Follow-up at 12 months: telephone contact -------------------------------------------------------------------------------- 24 
4.3 
Data collection of patients excluded from registry ------------------------------------------------------------------------------ 24 
5. Medications ------------------------------------------------------------------------------------------------ 25 
6. Procedure --------------------------------------------------------------------------------------------------- 26 
6.1 Preparation prior to rotational atherectomy ------------------------------------------------------------------------------------------- 26 
6.2 Rotational atherectomy operational guide -------------------------------------------------------------------------------------------- 27 
6.2.1 System setup ------------------------------------------------------------------------------------------------------------------------ 27 
6.2.2 Procedure preparation ----------------------------------------------------------------------------------------------------------- 27 
6.2.3 Burr positioning and ablation procedure------------------------------------------------------------------------------------ 27 
6.2.4 Burr exchange and procedure completion ---------------------------------------------------------------------------------- 28 
6.3 Intracoronary imaging --------------------------------------------------------------------------------------------------------------------- 28 
6.4 PCI post rotational atherectomy --------------------------------------------------------------------------------------------------------- 28 
7.  Outcomes ------------------------------------------------------------------------------------------------- 28 
7.1 Primary efficacy endpoint ---------------------------------------------------------------------------------------------------------------- 28 
7.2 Secondary outcome measures ------------------------------------------------------------------------------------------------------------ 28 
8.  Safety assessment --------------------------------------------------------------------------------------- 29 
8.1 Primary safety endpoint ------------------------------------------------------------------------------------------------------------------- 29 
8.2 Safety index ---------------------------------------------------------------------------------------------------------------------------------- 29 
8.2 Reporting of adverse events -------------------------------------------------------------------------------------------------------------- 29 
9. Data management/ monitoring -------------------------------------------------------------------------- 29 
9.1 Accountability of data, completion and handover of data entry form ---------------------------------------------------------- 29 
9.2 Database design ----------------------------------------------------------------------------------------------------------------------------- 30 
9.3 Data entry ------------------------------------------------------------------------------------------------------------------------------------ 30 
9.4 Data verification ---------------------------------------------------------------------------------------------------------------------------- 30 
9.5 Data security --------------------------------------------------------------------------------------------------------------------------------- 30 

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9.6 Core laboratory (Angiography/ Intravascular imaging – IVUS/OCT) --------------------------------------------------------- 30 
9.7 Statistical analysis team ------------------------------------------------------------------------------------------------------------------- 30 
10.  Statistical analysis ------------------------------------------------------------------------------------- 30 
10.1 Sample size determination -------------------------------------------------------------------------------------------------------------- 30 
10.1.1 Statistical hypothesis ----------------------------------------------------------------------------------------------------------- 30 
10.1.2 Assumptions ---------------------------------------------------------------------------------------------------------------------- 31 
10.1.3 Final sample size ---------------------------------------------------------------------------------------------------------------- 31 
10.2 Statistical analysis of data set ---------------------------------------------------------------------------------------------------------- 31 
10.3 Statistical analysis plan ------------------------------------------------------------------------------------------------------------------ 32 
10.4 Primary efficacy endpoint analysis --------------------------------------------------------------------------------------------------- 32 
10.5 Secondary endpoint analysis ----------------------------------------------------------------------------------------------------------- 32 
10.6 Safety evaluation -------------------------------------------------------------------------------------------------------------------------- 32 
10.7 Sub-group analysis------------------------------------------------------------------------------------------------------------------------ 32 
11 Study Management --------------------------------------------------------------------------------------- 33 
11.1 Statement ----------------------------------------------------------------------------------------------------------------------------------- 33 
11.2 Ethical section ----------------------------------------------------------------------------------------------------------------------------- 33 
11.3 Verification of original records -------------------------------------------------------------------------------------------------------- 33 
11.4 Quality assurance and audit ------------------------------------------------------------------------------------------------------------- 33 
11.5 Informed Consent ------------------------------------------------------------------------------------------------------------------------- 34 
11.6 Modification of study protocol --------------------------------------------------------------------------------------------------------- 34 
11.7 Case report form (CRF) ----------------------------------------------------------------------------------------------------------------- 34 
11.8 Audit ----------------------------------------------------------------------------------------------------------------------------------------- 34 
11.9 Confidentiality agreement and patient privacy ------------------------------------------------------------------------------------- 34 
12.  Publications --------------------------------------------------------------------------------------------- 35 
13.  Data archiving ------------------------------------------------------------------------------------------ 35 

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14.  
References -------------------------------------------------------------------------------------------- 36 
15. Appendix -------------------------------------------------------------------------------------------------- 39 
15.1 Appendix 1: Contemporary data on RA-related complication rates ----------------------------------------------------------- 39 
15.2 Appendix 2: Definition and breakdown of RA-related complications -------------------------------------------------------- 40 
15.3 Appendix 3: List of study sites/ institutions involved in ROVUS Asia Registry ------------------------------------------- 42 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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List of abbreviations 
Abbreviations 
Name/ Organisation 
ACC 
American College of Cardiology 
ACS 
Acute coronary syndrome 
AE 
Adverse Event 
AHA 
American Heart Association 
ALT 
Alanine Transaminase 
AST 
Aspartate Transaminase 
BSC 
Boston Scientific Corporation 
CABG 
Coronary Artery Bypass Graft 
CAC 
Coronary artery calcium score 
CCS  
Canadian Cardiovascular Society 
CK 
Creatine Kinase 
CK-MB 
Creatine Kinase-Myoglobin Band 
CKD 
Chronic Kidney Disease 
CTRO 
Clinical Trials and Research Office 
CRF 
Case Report Form 
CTO 
Chronic Total Occlusion 
DAPT 
Dual Antiplatelet Therapy 
DES 
Drug-Eluting Stent 
DMC 
Data Monitoring Committee 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
FDA 
Food and Drug Administration 
ITT 
Intention to Treat 
IVUS 
Intravascular Ultrasound 
LAD 
Left Anterior Descending Coronary Artery 
LBBB 
Left Bundle Branch Block 
LCX 
Left Circumflex Coronary Artery 
LL 
Lesion length 
LM 
Left Main 
LVEF 
Left Ventricular Ejection Fraction 
MACE 
Major Adverse Cardiac Event 
MI 
Myocardial Infarction 
MLD 
Minimum Lumen Diameter 

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NHCS 
National Heart Centre Singapore 
NHLBI 
National Heart, Lung, and Blood Institute 
NSTEMI 
Non ST elevation Myocardial Infarction 
NTG 
Nitroglycerin 
OCT 
Optical Coherence Tomography 
PCI 
Percutaneous Coronary Intervention 
RA 
Rotational Atherectomy 
RCA 
Right Coronary Artery 
RVD 
Reference Vessel Diameter 
SAE 
Serious Adverse Event 
SCAI 
Society for Cardiovascular Angiography & 
Intervention 
ST 
Stent Thrombosis 
STEMI 
ST Elevation Myocardial Infarction 
TLF 
Target Lesion Failure 
TLR 
Target Lesion Revascularization 
TnI 
Troponin I 
TnT 
Troponin T 
TVF 
Target Vessel Failure 
TVR 
Target Vessel Revascularization 
UAP 
Unstable Angina Pectoris 
 
 
 
 
 
 
 
 
 
 

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1. Research background 
Coronary artery calcification is common especially in the elderly, diabetic or chronic kidney disease (CKD) 
population. While percutaneous coronary intervention (PCI) is a well-known and widely accepted treatment 
modality for obstructive coronary artery disease, severely calcified coronary lesions increase complexity of 
PCI with lower rates of procedural success as well as worse ischemic outcomes5. Given these technical 
challenges, lesion preparation strategies prior to stent implantation have been proposed to improve clinical 
outcomes with mixed results. 
Rotational atherectomy (RA; ROTABLATORTM OR ROTAPROTM) was first developed by David Auth and 
colleagues in 19886. The first RA procedure was performed in 1988 by Bertrand et. al. with subsequent US 
Food and Drug Administration (US FDA) approval for commercial use in 1993. Initial adoption RA was 
tempered by reports of high rates of restenosis in the pre-drug eluting stent (DES) era7,8 but there is a 
resurgence of interest given the rapidly ageing population with increasing complexity of coronary lesions 
encountered for percutaneous coronary intervention (PCI)9.  
In our current era of DES, the use of atherectomy has shifted from plaque debulking to plaque modification 
prior to PCI to promote stent expansion. This switch in emphasis was driven by outcomes from the Study to 
Determine Rotablator and Transluminal Angioplasty Strategy (STRATAS) and Coronary Angioplasty and 
Rotablator Atherectomy Trial (CARAT) clinical trials10,11. In these 2 trials, aggressive strategy with large 
burrs to achieve maximum debulking as lesion debulking strategy was associated with higher rates of 
angiographic complications (e.g. perforation), target lesions revascularization (TLR), and periprocedural CK-
MB release compared to lesion modification strategy with use of smaller burrs. This change in emphasis has 
allowed for widespread adoption of smaller burrs, guide catheters and sheaths without compromising safety 
and efficacy. Several studies have shown that RA can improve procedural success for PCI with no increase in 
adverse MACE outcomes12. As such, the 2011 ACC/AHA/SCAI guidelines on coronary intervention has 
given a Class IIa Evidence Level C recommendation for the use of RA in the treatment of heavily calcified 
coronary lesions13.  
Thus far, a staggering 900,000 RA procedures have been performed globally since its inception. The US, 
being the country which first developed RA, is currently carrying out approximately 20,000 cases of RA yearly 
with a utilization rate of 2% of all PCIs. Likewise, European centers have a comparable reported RA utilization 
rate of 2-3% while Japan’s utilization rate is roughly 2.8%14. China’s recent Rota Registry reported a much 
lower utilization rate of only 0.4%. However, thus far, there are limited reported data on utilization rates as 
well as outcomes in other Asian countries such as Singapore, Malaysia, etc.  
Therefore, this study aims to evaluate the real-world use of rotational atherectomy with or without other 
calcium debulking therapies in Asian countries in terms of clinical practice, safety as well as effectiveness 
outcomes and provide future basis/ platform for further research in this area.  

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1.1 Introduction to disease 
1.1.1 Disease Profile 
Coronary artery calcification (CAC) is a consequence of calcium phosphate composite deposition in the wall 
of coronary artery resulting in hardening. In these cases, PCI is challenging in view of difficulty to dilate or 
cross the lesions, often leading to suboptimal stent expansion, poor adherence and subsequently increasing 
incidence of major adverse cardiovascular events (MACE).  
1.1.2 Epidemiology and risk factors 
The prevalence of CAC is age and sex dependent and occurs in at least 90% of men and 67% of women aged 
70 years and above15,16. In multi-ethnic epidemiological studies, risk factors for CAC beyond age include 
hypertension, hyperlipidemia, diabetes and chronic kidney disease, similar to traditional cardiovascular risk 
factors17. Even after adjusting for the above risk factors, patients of Chinese descent are 77% more likely to 
have coronary artery calcifications compared to their Caucasian and Afro-American counterparts18. In addition, 
some retrospective studies have also shown that the risk factors aforementioned not only increase likelihood 
of CAC but also accelerates progression of calcification in patients with established coronary calcifications.  
1.1.3 Pathophysiology and classification 
Calcium regulatory mechanisms play an integral role not only in bone formation but also CAC. Vascular 
smooth muscles produce matrix vesicles which regulates mineralization in the vascular intima and media19,20. 
Other cell types e.g. microvascular pericytes also have the potential to generate mineralized matrix and 
undergo osteoblastic differentiation, leading to calcified deposits20.  
There are 2 widely recognized types of CAC i.e. atherosclerotic/intimal calcification and medial artery 
calcification. Intimal calcification occurs primarily due to atherosclerotic processes potentiated by 
inflammatory mediators as well as elevated lipid content in the lesions resulting in osteoblastic differentiation 
of the vascular smooth muscles19. On the other hand, medial artery calcification is linked to traditional risk 
factors of advanced age, diabetes and chronic kidney disease and results in arterial stiffness.  
1.1.4 Detection of CAC 
Coronary angiography has low-moderate sensitivity compared to IVUS or CT in detection of CAC but very 
high specificity. On the other hand, intravascular ultrasound (IVUS) is significantly more accurate with a 
sensitivity of at least 90 to 100% and specificity of 99 to 100%. Optical coherence tomography (OCT) provides 
higher resolution imaging (10-20 µm) than grayscale IVUS (150-200µm) with a comparable sensitivity of 96% 
and specificity of 97% for coronary calcification detection21. Both IVUS and OCT has been shown to be useful 
in evaluating calcium thickness and angle which predicts stent expansion22. A maximum calcium angle of 
more than 180 degrees with greater amount of calcium can lead to a smaller and more eccentric shaped stent 
area. However, as ultrasound does not penetrate calcium, IVUS is unable to determine calcium thickness. In 
contrast, as light penetrates calcium, OCT is able to determine calcium thickness in most of the cases as well 
as measure calcium volume23.  

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1.2 Introduction to treatment 
1.2.1 Rotational atherectomy 
To date, rotational atherectomy (RA) has been the most used atherectomy modality since its first inception in 
1988. RA uses high speed rotation (140,000 – 180,000 rpm) to ablate inelastic plaque, resulting in debris 
averaging 5µm in size24. The main focus of RA in the era of DES stent has been on plaque modification rather 
that plaque debulking with more papers showing improved PCI success rates. However, the use of RA has not 
been shown to reduce rates of MACE or stent restenosis25. The contemporary ROTAXUS trial showed that 
there is no difference in MACE outcomes at 2-year mark in calcified coronary lesion patients treated with or 
without RA but there were higher angiographic success rates compared to standalone PCI26. In the multicenter 
ROTATE trial, Kawamoto et. al. showed that planned RA is associated with shorter procedural/ fluoroscopy 
time, lower contrast volume as well as number of pre- dilation balloon catheters used compared to unplanned/ 
provisional RA27. Thus far, RA has been given a Class IIa Evidence level C for use in fibrotic or severely 
calcified coronary lesions that might not be crossed by a balloon catheter or adequately dilated before stent 
implantation in the 2011 ACC guidelines although the same guideline also cautions against routine use of RA 
in de novo lesions or in-stent restenosis (class III, level evidence A)13.  
1.3 Introduction to equipment 
1.3.1 Structure and basic principle of ROTABLATORTM 
The rotational atherectomy device (ROTABLATORTM OR ROTAPROTM; Boston Scientific, Natick, MA) 
comprises of the following components – console, foot pedal, air supply, advancer and the burr (Figure 1-4).  
There are several key components of the ROTABLATORTM. 
(1) Guidewire: Divided into 2 types i.e. floppy or extra support guidewire. Both guidewires have a 0.014” 
maximum spring tip diameter and an outer diameter of 0.009”.  
(2) Burr head: Diamond-encrusted elliptical burr with an outer diameter of 20µm with a wide range of burr 
sizes ranging from 1.25 – 2.5mm with 0.25mm increment in size from the smaller burr head to the next bigger 
burr head. 
(3) Polytetrafluoroethylene sheath tube: Has a diameter of 0.058”. This is used to encase the drive shaft to 
minimize driving axis injuries to the arteries when the drive shaft is introduced into the lesion. The RotaGlide 
lubricant is also used to lubricate the drive shaft to reduce friction and improve tactile feel. 
(4) Advancer: Atherectomy device that controls forward and backward motion of the burr head via the 
advancer knob.  
(5) Console: Important for controlling the rotational speed of burr head and monitoring duration of use.  
(6) Pedals: On and off pedals that is connected to the pressurized gas tank 

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(7) Air supply: Recommended to use compressed air or nitrogen with pressure regulator adjusted to 6.5-7.5bar 
and a gas flow rate that is not less than 140L/min. 
  
 
Figure 1: Console system of ROTABLATORTM and its components. Source: Boston Scientific user manual 
 
 
Figure 2: Foot pedal and air supply components of ROTABLATORTM. Source: Boston Scientific user manual 
 
 

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Figure 3: The rotablator advancer of ROTABLATORTM and its components. Source: Boston Scientific user 
manual 
 
 
Figure 4: ROTABLATORTM Burr heads in different sizes. Source: Boston Scientific user manual 
 
1.3.2 Principle 
RA ablates using a diamond-encrusted elliptical burr which rotates at speeds of 140,000 – 180,000 rpm driven 
by a helical draft shaft that is advanced across a lesion over a guidewire. The burr causes “differential cutting” 
and preferentially ablates hard, inelastic, calcified plaques that are unable to stretch away from the RA burr 
compared to healthy arterial tissue (Figure 5). While RA has been shown to selectively remove calcium 
deposits, IVUS studies have also shown that adjacent endothelial cells may be abraded during the process 
leading to vasospasm28. However, high speed RA generally generates low friction during the creation of 
smooth lumen-atheroma interface with incidence of coronary artery dissection significantly lower than balloon 

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angioplasty alone28. On the other hand, low speed RA tend to cause fissures and debris formation between 
plaque and membrane, creating an irregular wall in the process. 
 
Figure 5: Differential cutting of ROTABLATORTM. Source: Barbato et.al. 2017 
 
At rotational speed of 160,000 to 200,000 rpm, the RA burr head will pulverize atherosclerotic plaque into 
granules. Studies have found that a vast majority of the particles produced during atherectomy have a < 10-
15µm size which will be cleared by the phagocyte system. It does not cause capillary thrombosis nor 
negatively affect left ventricular function. Despite this, the heat generated during the forward grinding can 
lower rotational speed with possibility of generating larger particles especially when the rotational speed drops 
below 75,000 rpm.   
2. Study Aim 
1 To describe the use of RA in real world practice in Asia 
2 To determine predictors of procedural success 
3 To determine predictors of major procedural complications: perforation and no-reflow phenomenon 
4 To assess the clinical outcome of patients undergoing RA for heavily calcified coronary lesions. 
3. Selection and exit criteria 
3.1 Inclusion criteria 
Subjects MUST fulfill ALL of the following requirements in order to be eligible for the study:  
1. At least 21 years of age of any gender 
2. Able to understand and sign an informed consent form 
3. Presence of clinical indication for percutaneous coronary intervention (PCI) and/or stent placement 
4. Subjects willing to comply with all research and follow-up requirements 
5. Angiographic criteria (ONE of the following criteria MUST be met) 
a. Target lesions visually have at least moderate calcifications* 

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b. Target lesion balloon dilatation failure 
c. Inability of devices (microcatheters, balloon, stents or imaging devices) to pass through the 
target lesion 
d. Intravascular imaging shows severe calcifications* 
6. Procedural criteria 
a. All patients treated with RA with or without other forms of debulking therapy 
*Moderate calcification is defined as radio-opacities noted only during cardiac cycle prior to contrast injection 
whereas severe calcification is defined as radio-opacities seen without cardiac motion prior to contrast 
injection, usually affecting both sides of the arterial lumen1.   
3.2 Exclusion criteria 
1. Patient unable to or decline to give consent 
3.3 Exit criteria 
Participation in this study is optional and patients are free to withdraw their participation from this study at 
any time point during the study process without the need to provide any justification. Withdrawal from this 
study will not affect participants’ future medical treatment. 
Patients who have withdrawn their participation are not obligated to continue further follow-up and will not 
be replaced by new participants in this study. A reasonable sample size has been calculated to account for 
patient attrition.  
Should the reason for withdrawal from the study be due to issues related to either safety or effectiveness of 
the study device, the investigator shall obtain a new separate consent from the subject, independent of the 
original study consent, to continue tracking his/her clinical progress/ situation.  
3.4 Early termination 
The study sponsors reserve the right to terminate the study at any stage should the need arise but will exercise 
this right only for valid scientific or administrative reasons. The study sponsors, relevant ethics committee and 
regulatory agencies (if applicable) will be notified in writing at the time of study termination. 
3.4.1 Study termination criteria 
Study termination refers to the cessation of all tests or follow-up during the progress of a clinical trial program. 
The main purpose is to protect the rights and interest of clinical subjects, maintain quality assurance testing 
and to minimize unnecessary economic losses. 
Causes for early termination includes (but not limited to) the following: 
1. Inability to continue research on grounds of medical and/or ethical considerations 
2. Slow enrollment progress such that the study cannot be completed within a reasonable and acceptable time 
window 

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3. Decision from Ethics Committee/Board to terminate the study 
4. Availability of new information which impacts standard of care (such as product safety/ performance) 
5. Boston Scientific Corporation decides to suspend/ halt the development of the study/ test equipment 
 
3.4.2 Study site termination criteria 
If a study/ research site (i) is unable to recruit any patients, (ii) has an enrollment rate that is significantly 
lower than expected (iii) violated the study protocol without due justification or in spite of remedial measures, 
the study sponsors/ National Heart Centre Singapore (NHCS) reserve the right to remove the study site from 
the research study.  
4. Study design 
4.1 Research design 
This is a prospective observational multicenter cohort study of all patients with calcified coronary lesions 
undergoing RA in participating centres across Asia. Patients will be required to provide informed consent for 
data collection, including follow-up data and uploading of data on a web-based data collection platform (de-
identified).  
Operators/ institution coordinators will fill up hardcopy or electronic (web-based) forms including patient’s 
baseline demographics, co-morbidities, clinical data, laboratory test results, echocardiography results, 
coronary angiography findings with subsequent interventions performed as well as follow-up clinical and 
laboratory results.  
Note that while detailed data for individual patients will only be collected if there is informed consent, data 
from each institution will also be collected for aggregate data regarding procedural volume (eg. total cases 
with debulking therapy and specifically for ROTABLATORTM). This will give a sense of representativeness 
of data collected. This screening data will also include the following fields: age, gender, ethnicity, co-
morbidities, target vessel, prior revascularization (PCI/CABG), clinical presentation, procedural urgency, 
angiographic procedural details (RA and PCI) and in-hospital complication and mortality. The use of this 
retrospective data will require appropriate approval and will only utilize anonymized data. Only in-hospital 
data will be obtained and no follow up data is required from these controls. 
Should these data not be available in any of the participating sites, a minimum baseline demographics, 
procedural and inpatient outcome data with reasons for non-participation in registry should be provided for 
records purposes. This shall be accepted as a limitation of the study. Sub-site analysis may be performed in 
centres with availability of all data in this group of patients to address generalisability of the data collected. 

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Figure 6: Data collection workflow for (i) patients who provide consent vs (ii) patients who declined to provide 
consent/ unable to give timely consent in view of unexpected demise 
4.2 Study stages 
4.2.1 Index visit: Within 48 hours of PCI 
The following information will be captured during this index visit:  
1. Demographics: Age, gender, ethnicity 
2. Clinical characteristics: Clinical presentation (STEMI, NSTEMI, UAP, Angina, cardiac arrest), 
Symptoms (CCS angina score), Co-morbidities (diabetes mellitus, hypertension, hyperlipidemia, atrial 
fibrillation, smoking status, CKD/ ESRF, prior MI, prior PCI, prior CABG, prior CVA) 
3. Laboratory results: full blood count, creatinine, electrolytes, fasting lipids/ glucose, HbA1c, cardiac 
injury markers i.e troponin T or I, CK, CK-MB) 
a. If either troponin T or I is to be measured AFTER PCI with rotational atherectomy, a total of 
3 sets are recommended at specific time intervals of 0-1 hours (1st set), 4-8 hours (2nd set) and 
12-24 hours (3rd set) POST-PCI to ensure uniformity of sample collection across all sites. 
b. Sites are to also provide the upper limit of normal values for their laboratory assay tests. 
4. Medications: prior to PCI, during PCI, on discharge 
5. ECGs (a post procedural ECG is required) 
6. Echocardiographic data (LVEF) 
7. Procedural data: Coronary anatomy (artery dominance, number of diseased vessels, presence of bypass 
grafts), target lesion (location by artery/grafts, proximal vs mid vs distal, branches (ramus, diagonal, 
OM, RPDA, graft)), rotational atherectomy (lubricant, burr size, run time, burr speed, number of passes, 
maximum rotational speed), adjunctive devices (guideliners, guide size, guide shape), PCI (type of 
PCI performed - POBA vs DEB vs DES, number of stents, pre and post-dilatation, stent overlap), 

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angiographic outcomes (TIMI flow, angiographic complications) procedural details (fluoroscopic 
duration, total contrast media) 
8. Intravascular imaging data (OCT/ IVUS) 
a. Sites will also send CDs of their angiograms and intravascular imaging 
9. Outcomes data: Primary (residual stenosis in treated segment with TIMI 3 flow without mortality), 
Secondary (Death, periprocedural MI, complications (coronary perforation, no reflow, slow flow)  
10. Primary operator data: ie. Operator initials (further anonymized prior to analysis), Age band, years of 
interventional cardiology practice, number of procedures. (PCI) performed preceding year (range), 
approximate number of rotablator performed last year (range) 
11. Limited hospital data: number of years with rotablator therapy, approximate number of PCI preceding 
year, number of rotablator preceding year, availability of orbital atherectomy/ shockwave lithotripsy 
Patient will also be asked to sign study consent form (in addition to institutional procedural consent form) to 
certify agreement to participate in current research study.  
4.2.2 Follow-up at 12 months: telephone contact 
The following information will be captured during this 12-month follow-up visit: Symptoms (CCS score), 
medications (antiplatelet therapy, statins, non-statins LDL lowering therapy), outcomes (death, MI, TLR, stent 
thrombosis, and stroke). 
4.3 Data collection of patients excluded from registry 
1. Demographics: Age, gender, ethnicity 
2. Abbreviated clinical characteristics: Clinical presentation (STEMI, NSTEMI, UAP, Angina, cardiac 
arrest), Symptoms (CCS score), Co-morbidities (diabetes mellitus, hypertension, hyperlipidemia, atrial 
fibrillation, smoking status, CKD/ ESRF, prior MI, prior PCI, prior CABG, prior CVA) 
3. Abbreviated laboratory results: full blood count, creatinine, fasting lipids, HbA1c, cardiac injury 
markers i.e troponin T or I, CK, CK-MB) 
4. Medications: on discharge 
5. Echocardiographic data (LVEF) 
6. Procedural data: Coronary anatomy (artery dominance, number of diseased vessels, presence of bypass 
grafts), target lesion (location by artery/grafts, proximal vs mid vs distal, branches (ramus, diagonal, 
OM, RPDA, graft)), use of alternative calcium debulking devices, PCI (type of PCI performed - POBA 
vs DEB vs DES, number of stents, pre and post-dilatation, stent overlap), angiographic outcomes 
(TIMI flow, angiographic complications) procedural details (fluoroscopic duration, total contrast 
media) 
7. Outcomes data: Primary (residual stenosis in treated segment with TIMI 3 flow without mortality), 
Secondary (Death, periprocedural MI, complications (coronary perforation, no reflow, slow flow)  
 
 

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5. Medications 
All participants are recommended to be initiated on dual antiplatelet therapy (DAPT), one of which must be 
aspirin and the other is a P2Y12 inhibitor (clopidogrel or ticagrelor) prior to PCI. The duration of DAPT is to 
be determined by the interventionist. The following recommendations are for physician reference. 
(i) 
Aspirin 
If the subject has been taking aspirin daily for ≥ 72 hours prior to PCI, loading of aspirin is not necessary. 
If the subject is aspirin naïve or has taken aspirin for less than 72 hours prior to PCI, loading of aspirin prior 
to PCI is recommended. Dose of aspirin loading is to be determined by the interventionist.  
If aspirin is to be loaded, it is recommended to be at least 2-hour prior to PCI.  
Patient should be continued on long term aspirin subsequently. 
(ii) 
P2Y12 inhibitors 
If the subject has taken P2Y12 inhibitors (e.g. clopidogrel, ticagrelor or prasugrel) ≥ 7 days, loading of P2Y12 
is not necessary. 
If the subject is P2Y12 inhibitor naïve or has not taken P2Y12 daily for at least 7 days, loading of P2Y12 prior 
to the PCI is recommended. The dose of P2Y12 is to be determined by the interventionist. Generally, at least 
300-600mg of clopidogrel is required for loading, while ticagrelor loading dose is 180mg.  
If P2Y12 is to be loaded, it is recommended to be at least 2-hour prior to PCI for both clopidogrel and ticagrelor. 
For prasugrel, loading dose of 60mg should only be given once coronary anatomy is known and PCI is planned 
on table.  
The subject should be treated with P2Y12 inhibitor for a minimum duration of 6 months and continued up to 
at least 12 months if the risk of bleeding is deemed to be low.   
(iii) 
Intraprocedural anticoagulation 
The choice of anticoagulation is dependent on operator’s discretion to maintain a recommended ACT range 
of 200-300 seconds. 
(iv) 
Intracoronary medications 
The administration of intracoronary glyceryl trinitrate (GTN) is recommended prior to coronary angiography 
of both left and right coronary artery system. 
The use and choice of other intracoronary vasodilators such as CCB, adenosine is left up to operator’s 
discretion/ individual site practice. 
(v) 
Guideline directed medical therapy 

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Other medications such as statins, ACEi/ ARB, Beta-blockers, calcium antagonists and other drugs use are as 
per international or local guidelines such as ACC or ESC.  
6. Procedure 
6.1 Preparation prior to rotational atherectomy 
Access planning for an individual patient must balance the need to provide sufficient support for RA and 
vascular complications that may arise. Generally, a 6 Fr system is adequate to support RA in most cases and 
is able to accommodate burr sizes up to 1.75mm, thereby permitting either trans-radial or trans-femoral 
approach. Radial approach has been associated with equivalent procedural success to that of femoral 
access29,30. As such, radial approach should not be abandoned in patients who have planned RA. In addition, 
additional support can be enhanced by either using a long sheath, supportive guide catheter or a child-in-
mother catheter. In contrary, if a 2.0mm or larger burr size is required or complex bifurcation PCI is planned, 
a 7Fr or larger catheter may be required, by which a trans-femoral approach may be preferred.  
Prior to RA, it is paramount to position a RotaWire across the target lesion with its tip placed as far distally 
as possible. Primary wiring of target lesion with RotaWire can be challenging and thus initial wiring with 
either a workhorse or specialty 0.014” coronary guidewire within a micro-exchange catheter or over-the-wire 
balloon may be easier, subsequently permitting exchange for a RotaWire while concurrently divulging 
crossing properties of the lesion. In situations whereby the microcatheter is unable to cross the lesion, it is 
advisable to perform RA with the smallest (1.25mm) burr.  
Burr size selection is key to procedural success. As shown in STRATAS and CARAT trial, smaller burrs (with 
burr: artery ratio < 0.7) have comparable angiographic and procedural success rates to larger burrs but with 
fewer angiographic complications, less peri-procedural myocardial injury, use of smaller sheaths and guide 
catheters with consequently lower vascular and bleeding complications10,11. A stepped burr strategy beginning 
with 1.25 or 1.50 burr with gradual escalation in size up to maximal burr: artery ratio of 0.7 is recommended 
especially in cases for which micro-exchange catheter will not cross the lesion or lesions with severe 
angulation, tortuosity or eccentricity.  
During the RA process, a flush solution comprising of heparinized saline with RotaGlide lubricant is also 
recommended to lubricate device motion, prevent sudden decelerations and reduce heat generation. In some 
instances, vasodilators such as nitroglycerin (50-200µg), verapamil (100-200µg, up to a total amount of 1.0 – 
1.5mg) or diltiazem (0.5-2.5mg, up to 5-10mg) can be incorporated into the flush solution to further reduce 
risk of microvascular obstruction.  
RA involving right coronary artery, left dominant circumflex or use of large burr head (> 2.25mm) are prone 
to transient microvascular ischemia with consequent risk of bradycardia and conduction blocks. In such 
situations, prophylactic temporary pacing may be considered. Bradycardia in these situations occur especially 
during forward grinding spin of the burr and usually recovers after 5 to 60 seconds post cessation of 
atherectomy or on coughing.  

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6.2 Rotational atherectomy operational guide 
6.2.1 System setup 
Plug in console and turn on power switch. Connect the air supply hose to compressed air or nitrogen (minimum 
of 500 PSI in tank per procedure with 90-110 PSI flowing to console). Connect all 3 Dynaglide foot pedal 
hoses to the console (green and blue to the back while pink to the front). Then, connect the fiber-optic cables 
and air -line to the front of the console. Add the RotaGlide lubricant and other adjunctive vasodilators (as 
indicated) to the 1-liter sterile saline bag and connect it to the ROTABLATORTM infusion port and pressurize 
the bag to 150 - 200mmHg.  
6.2.2 Procedure preparation 
Place both the guide sheath and guidewire sequentially into the target vessel. Advance the guidewire beyond 
the target lesion and backload burr, stopping just proximal to the sheath. Grasp the proximal tip of the 
guidewire and thread this end into the hole in the tip of the burr. Continue feeding the wire into the catheter 
until it appears at the rear of the advancer. Then, grasp the exposed wire and pull it gently until the burr is a 
few centimeters from the entrance to the guide sheath/ introducer sheath. Thereafter, attach a wireclip Torquer 
to the end of the guidewire. Ensure that advancer knob is fixed at 2cm from the distal end. Connect the air 
hose, fiber optic cable and saline infusion port subsequently.  
Test the system outside the subject’s body with foot pedal activated. Firstly, check the drip from the catheter 
sheath tip and beneath the advancer. Next, set the burr speed to desired RPM level followed by ensuring the 
free movement of the advancer knob. Finally, check that the wire is visible out of the advancer with torquer 
clip attached. Tug on wire during rotating to ensure brake is activated.  
6.2.3 Burr positioning and ablation procedure 
Under fluoroscopic guidance, gently push the burr through the guide sheath to a point proximally to the target 
lesion. Check that the burr size is compatible with vessel diameter by contrast injection. Stop the burr in free 
lumen and when the burr is 1-2cm proximal to the target lesion, retract the advancer knob fully to prevent the 
burr from darting forward during first activation.  
Fully depress the foot pedal to activate the burr. Adjust your foot for optimum position on the foot pedal. 
Recheck the rotational speed reading to verify that the rotation rate is appropriate for the burr size and lesion 
type. Generally smaller burrs 1.25mm – 2.0mm burrs require rotational speed of 160,000-180,000 rpm 
whereas larger burrs of at least 2.15mm require lower rotational speed of 140,000-180,000 rpm.  
Slowly push the advancer knob forward and observe progress of burr fluoroscopically. Advance in such a 
manner such that the burr speed does not decrease lower than beyond 5000 rpm from the unloaded platform 
speed. This can be assessed by firstly observing the console display initially followed by listening to the 
corresponding drop in audible pitch. It is recommended to advance and retreat the burr no more than 3cm at a 
time in a smooth pecking motion. Care should be taken to engage the lesion only minimally when resistance 
is met. Short individual runs of less than 30 seconds are recommended with total rotational procedure time 
not to exceed five minutes. In between each interval, small amount of contrast should be injected to assess for 
burr head position, confirm presence of coronary blood flow and evidence of vascular complications such as 

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perforation in addition to flushing microparticles to distal ends of vessels. If resistance to motion is 
encountered, retract the burr and stop treatment immediately. Reassess situation using fluoroscopy. Decision 
to stop further atherectomy attempts using current burr is dependent on absence of resistance felt throughout 
the entire length of diseased segments or rotational speed was not significant decreased during the run.  
6.2.4 Burr exchange and procedure completion 
When satisfactory RA attempt has been made using the first burr, activate the Dynaglide feature by pressing 
the button on the foot pedal to exchange burr. When this feature is activated, the RA system will rotate at 
reduced speed of 60,000 – 90,000 rpm and the guidewire will advance readily when the advancer is withdrawn. 
The guidewire must be held firmly using the wireclip Torquer whenever the advancer is operated under the 
Dynaglide mode. With the wireclip Torquer/guidewire combination in docking port, depress the brake defeat 
button and push forward on the Torquer until it stops, hence locking the brake defeat button in a depressed 
position. Thereafter, the burr can be withdrawn over the guidewire until a 7cm or larger loop of wire remains. 
Release the foot pedal then. Thereafter, switch to a larger burr if required or proceed with stent placement if 
desired treatment outcome has been achieved.  
6.3 Intracoronary imaging  
Where appropriate, the preferred imaging platform is intravascular ultrasound (IVUS), either with Opticross 
or Opticross HD. However, the final selection on the use of IVUS or optical coherence tomography (OCT) 
is subject to operator’s discretion based on angiographic findings. 
6.4 PCI post rotational atherectomy 
For PCI, the preferred type of stent is drug eluting stent (DES), either with SYNERGY or SYNERGY XD per 
commercial availability. However, the final selection on stent type/ brand is subject to operator’s discretion 
based on clinical indication as well as angiographic findings. 
7.  Outcomes 
7.1 Primary efficacy endpoint 
Procedural success defined as < 20% residual stenosis in treated segment without on-table mortality with 
TIMI 3 flow  
7.2 Secondary outcome measures 
1. Death (in-hospital and at 1-year follow-up) 
2. Periprocedural myocardial infarction (MI) defined as either (within 48 hours of procedure) 
a. Peak CK-MB ≥ 10x ULN OR ≥ 5x ULN + new pathologic Q waves in ≥ 2 contiguous leads/ new 
persistent LBBB2 OR 
b. Peak Troponin T or I > 5x ULN + new pathologic Q waves/ ischemic ECG changes3 
3. Complications: Significant coronary perforation defined as (within 48 hours of procedure) 
a. At least Type II, III or III CS based on Ellis classification4 

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4. Complication: no-reflow or slow flow (within 48 hours of procedure) 
5. Procedural time defined as  
a. Time of guide engagement to removal of guide.  
8.  Safety assessment 
8.1 Primary safety endpoint 
All RA-related complication rate 
8.2 Safety index 
The following safety data will be collected over the 12-months follow-up period: 
1. All-cause death (cardiac/non-cardiac/sudden death/unknown) 
2. Myocardial infarction 
a. Subset analysis on target vessel MI (TVMI) in those with data on repeat coronary angiography 
3. Target lesion revascularization (TLR) 
4. Definite/probable stent thrombosis 
5. Major cardiovascular events (MACE)  
a. Defined as composite endpoint of cardiac death, MI, TLR, and stent thrombosis 
6. Stroke 
7. Device related adverse events  
a. Includes but are not limited to rotawire fracture/ breakage, rotawire unravelling/ fraying, burr 
dislodgement/ fracture and burr entrapment  
 
8.2 Reporting of adverse events 
The events listed in Section 12.1 are all considered serious adverse events (SAE). However, as the procedure 
is done in accordance to standard of care and RA has been extensively used in clinical settings worldwide, 
these safety data will only be collected for the purposes of this registry and does not require safety reporting 
to Institutional Review Board (IRB) or Ethics Committee (EC). 
Should there be an SAE deemed reportable by the respective site PI, the site PIs are to report the event(s) to 
their respective local IRB or EC as per their own prevailing safety reporting guidelines.   
9. Data management/ monitoring 
9.1 Accountability of data, completion and handover of data entry form 
All participants who have signed the study consent form and are eligible for participation will have all of the 
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9.2 Database design 
A secure web-based database application i.e. REDCap will be used to collate study data and for the purposes 
of study analysis. 
9.3 Data entry 
Clinical research coordinator (CRC) and/or authorized study investigators will be able to input and edit the 
data from the case reporting form into the electronic database as accurately as possible. 
9.4 Data verification 
The database will be reviewed by the site investigators as well as lead investigators to ensure the veracity of 
the data collected. If there are any discrepancies noted, a manual enquiry will be raised and will be discussed 
between involved study sites and the primary study site i.e. NHCS. 
9.5 Data security 
After the CRC or researcher fills in the data completely, data managers, statisticians and lead PI will review 
the data and finalise the analysis/ outcomes of the study population before locking/ encrypting the database. 
9.6 Core laboratory (Angiography/ Intravascular imaging – IVUS/OCT) 
Dr Chin Chee Yang 
Consultant 
National Heart Centre Singapore 
9.7 Statistical analysis team 
Gao Fei 
National Heart Research Institute (NHRI) 
National Heart Centre Singapore (NHCS), Singapore 
 
Dr. Tomohiro Shinozaki, PhD, MPH.  
Department of Information and Computer Technology, Faculty of Engineering, Tokyo University of Science, 
Tokyo, Japan. 
10.  Statistical analysis 
10.1 Sample size determination 
10.1.1 Statistical hypothesis 
The RA-related complications occur in 5% of all the RA procedures in Asian PCI centres  

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NOTE: See Appendix 1 and 2 for contemporary data on RA-related complication rates justifying selection of 
5% incidence rate for all RA-related complications31. 
10.1.2 Assumptions 
The target sample size is calculated based on the following assumptions: 
1. The proportion of RA-related complications is 5% 
2. 95% confidence intervals width is 3%.  
3. Up to 20% of patients are assumed to drop out of this study 
 
 
 
Sample 
 
 
 
 
 
 
Confidence 
Size 
Target 
Actual 
Proportion 
Lower 
Upper 
Width if 
Level 
(N) 
Width 
Width 
(P) 
Limit 
Limit 
P = 0.5 
0.95 
1118 
0.02 
0.02 
0.03 
0.02 
0.04 
0.059 
0.95 
1476 
0.02 
0.02 
0.04 
0.03 
0.05 
0.051 
0.95 
1825 
0.02 
0.02 
0.05 
0.04 
0.06 
0.046 
0.95 
2167 
0.02 
0.02 
0.06 
0.05 
0.07 
0.042 
0.95 
497 
0.03 
0.03 
0.03 
0.015 
0.045 
0.088 
0.95 
656 
0.03 
0.03 
0.04 
0.025 
0.055 
0.077 
0.95 
811 
0.03 
0.03 
0.05 
0.035 
0.065 
0.069 
0.95 
963 
0.03 
0.03 
0.06 
0.045 
0.075 
0.063 
0.95 
280 
0.04 
0.04 
0.03 
0.01 
0.05 
0.117 
0.95 
369 
0.04 
0.04 
0.04 
0.02 
0.06 
0.102 
0.95 
457 
0.04 
0.04 
0.05 
0.03 
0.07 
0.092 
0.95 
542 
0.04 
0.04 
0.06 
0.04 
0.08 
0.084 
Table 1: Numeric Results for Two-Sided Confidence Intervals for One Proportion Confidence Interval 
Formula: Simple Asymptotic 
10.1.3 Final sample size 
1000 subjects 
10.2 Statistical analysis of data set 
Full analysis set (FAS): Refers to the set of analysis established in accordance to intention-to-treat (ITT) 
principle. All subjects who signed informed consent form and met all the inclusion criteria with the use of RA 
with or without other calcium debulking therapies will be included in this analysis. For subjects who are unable 
to complete the study follow-up, the primary endpoint will be based on the last observation carry forward 
method.  

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Per-protocol set (PPS): Refers to the set of analysis pertaining to the whole treated study population who have 
completed the study excluding those not fulfilling selection criteria or use of devices/ equipments not provided 
in this research study. 
Safety analysis set (SS): Refers to all study subjects that have been evaluated at least once for safety outcome. 
Those with missing data will not be carried forward. 
Efficacy analysis will be carried out based on the full analysis set and the per-protocol set.  
10.3 Statistical analysis plan 
All demographic data, clinical characteristics, laboratory results, medications, electrocardiography, imaging, 
angiographic data, intravascular data, outcomes, primary operator data and hospital data will be analyzed. 
Continuous variables will be described using mean, median, standard deviation, interquartile range (IQR) and 
minimum/maximum values. Discrete variables will be described using frequency tables. A t-test will be used 
to assess if there is a significant difference (p<0.05) in continuous data and a chi-square test will be used in 
discrete data. 
All statistical comparisons will be performed using two-sided tests with a significance level of 0.05. Statistical 
analysis will be performed using STATA or SAS software. 
10.4 Primary efficacy endpoint analysis 
Procedural success rate will be estimated and reported with 95% confidence interval.  
10.5 Secondary endpoint analysis 
All event rates within 48 hours of procedure will be estimated and reported with 95% confidence interval. 
10.6 Safety evaluation 
Kaplan-Meier curve will be used to construct 1-year cumulative event rates with 95% confidence interval.  
 
10.7 Sub-group analysis 
This study will collect all subjects who have undergone calcium debulking therapy and evaluate real-world 
clinical outcomes 
The following sub-groups (but not limited to) may be utilised for analysis: 
(i) 
Acute coronary syndrome 
(ii) 
Lesion length 
(iii) 
Bifurcation lesions 
(iv) 
Multiple overlapping stents (≥ 2 stents for each epicardial coronary artery) 
(v) 
Chronic kidney disease 

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(vi) 
Multivessel disease (≥ 2 vessel CAD) 
(vii) 
Left main (LM) equivalent 
(viii) Chronic total occlusions (CTO) 
(ix) 
Severely impaired LVEF i.e. ≤ 30% 
(x) 
IVUS subgroup 
11 Study Management 
11.1 Statement 
This study complies with the requirements of the current Declaration of Helsinki as well as other relevant 
national regulations 
11.2 Ethical section 
In accordance to national policies and regulations, the site study investigators must provide the Ethics 
Committee with relevant study documents as required. 
A copy of the approval from the local Ethics Committee together with the list of review documents must be 
submitted to the primary site i.e. National Heart Centre Singapore (NHCS) before the device will be delivered 
to the study sites. The approval document from the Ethics Committee must also be accompanied by a list 
detailing all the members involved in the approval and their respective roles in the committee. 
Approval from Ethics Committee is mandatory prior to initiation of clinical trial. 
Any changes to the study protocol must be submitted to the Ethics Committee for approval. Throughout the 
study, any serious or unintended adverse events pertaining to safety of patients must be reported to the Ethics 
Committee. 
11.3 Verification of original records 
Study investigators must ensure that all data obtained during this study is properly secured and encrypted to 
protect the privacy of subjects involved. In addition, study investigators must also consent to audit/ verification 
of database by auditors/ inspectors to ensure accuracy and accountability of data collected as well as update 
on progress of study. In the unfortunate event that the original records cannot be verified, the study investigator 
will need to assist the auditor in quality control of the data. 
11.4 Quality assurance and audit 
The study will be audited by personnel authorized by National Heart Centre Singapore/ Boston Scientific 
Corporation. Quality auditors will have access to all medical records, research-related documents/ 
correspondences, and informed consent for this study.  

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11.5 Informed Consent 
It is the responsibility of the study investigator to explain the purpose, methods, benefits, and potential risks 
of this clinical trial to each subject. An informed consent (both written and verbal) must be obtained from the 
subject prior to inclusion in this study. Informed consent must be dated and signed by the participant him or 
herself. Participants who decline to provide informed consent will be excluded from this study. A copy of the 
signed inform consent and information sheet will be given to the participants. 
By signing the informed consent form, the participant has agreed to allow National Heart Centre Singapore 
and Boston Scientific Corporation auditors to verify the data.  
11.6 Modification of study protocol 
Once the final version of the study protocol has been agreed upon, any further modifications to the protocol 
will be subjected to a detailed review of proposed changes with the proposer to initial against the proposed 
changes with date and time.  
All proposed changes must be approved in writing by the Ethics Committee. All documents will need to be 
submitted to National Heart Centre Singapore (NHCS) 
11.7 Case report form (CRF) 
Operators/ institution coordinators will fill up hardcopy and/or electronic (web-based) forms including 
patient’s baseline demographics, co-morbidities, clinical data, laboratory test results, echocardiography results, 
coronary angiography findings with subsequent interventions performed as well as follow-up clinical and 
laboratory results. Note that while detailed data for individual patients will only be collected if there is 
informed consent, data from each institution will also be collected for aggregate data regarding procedural 
volume (eg. Of total cased with debulking therapy and specifically for rotablator). This will give a sense of 
representativeness of data collected. 
11.8 Audit 
NHCS will request for participating centers to provide updates on recruitment progress as well as clinical 
outcomes of existing patients at regular intervals.  
Finally, all original data collection forms, records, laboratory results must be readily available at every time 
point to all study investigators and auditors.  
11.9 Confidentiality agreement and patient privacy 
Study investigators must ensure the confidentiality of the information provided or disclose the requisite 
information as required with the authorization from NHCS. 
The researcher must not disclose any confidential information obtained from NHCS, Boston Scientific, or 
from this study to third parties.  

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Researcher musts ensure that the data is anonymized. It is imperative that all documents submitted to NHCS 
or Boston Scientific is labelled with study index number and that participants personal details cannot be 
retrieved from the documents.  
12.  Publications 
National Heart Centre Singapore (NHCS), as the primary site, will hold exclusive rights to this study. All 
study site investigators will be involved in the drafting of manuscripts related to this study. As this is a 
multicenter study, investigators are not allowed to write/ submit a manuscript until the final analysis from the 
multicenter study is completed, unless it is approved by NHCS. With regards to manuscripts and publications, 
NHCS reserves the right to determine the final outcome.  
13.  Data archiving 
In accordance to regulations, study investigators should properly preserve the original records of the research. 
All clinical research data must be kept for at least 5 years from the start of data collection. It is the 
responsibility of the primary site to inform the study investigators when such information is no longer required 
to be saved.  
 
 
 
 
 
 
 
 
 
 
 
 
 

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14.  References 
1.  
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Cardiology. WB Saunders, Philaedelphia, PA; 1994:1052-1068. 
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infarction after coronary revascularization: An expert consensus document from the society for 
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Thygesen K, Alpert JS, Jaffe AS, et al. Fourth Universal Definition of Myocardial Infarction (2018). J 
Am Coll Cardiol. Published online 2018. doi:10.1016/j.jacc.2018.08.1038 
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classification, 
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calcified vessels in acute coronary syndromes: Pooled analysis from the HORIZONS-AMI 
(Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) and 
ACUITY 
(Acute 
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6.  
Hansen DD, Auth DC, Vracko R, Ritchie JL. Rotational atherectomy in atherosclerotic rabbit iliac 
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7.  
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coronary lesions at a single center: Excimer laser, rotational atherectomy, and balloon angioplasty 
comparison (ERBAC) study. Circulation. Published online 1997. doi:10.1161/01.CIR.96.1.91 
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Dill T, Dietz U, Hamm CW, et al. A randomized comparison of balloon angioplasty versus rotational 
atherectomy in complex coronary lesions (COBRA study). Eur Heart J. Published online 2000. 
doi:10.1053/euhj.2000.2242 
9.  
Sharma SK, Tomey MI, Teirstein PS, et al. North American Expert Review of Rotational Atherectomy. 
Circ Cardiovasc Interv. Published online 2019. doi:10.1161/CIRCINTERVENTIONS.118.007448 
10.  Whitlow PL, Bass TA, Kipperman RM, et al. Results of the study to determine rotablator and 
transluminal angioplasty strategy (STRATAS). Am J Cardiol. Published online 2001. 
doi:10.1016/S0002-9149(00)01486-7 
11.  Safian RD, Feldman T, Muller DWM, et al. Coronary Angioplasty and Rotablator Atherectomy Trial 
(CARAT): Immediate and late results of a prospective multicenter randomized trial. Catheter 
Cardiovasc Interv. Published online 2001. doi:10.1002/ccd.1151 

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12.  Abdel-Wahab M, Richardt G, Joachim Büttner H, et al. High-speed rotational atherectomy before 
paclitaxel-eluting stent implantation in complex calcified coronary lesions: The randomized 
ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary 
Artery Disease) trial. JACC Cardiovasc Interv. Published online 2013. doi:10.1016/j.jcin.2012.07.017 
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coronary intervention. J Am Coll Cardiol. Published online 2011. doi:10.1016/j.jacc.2011.08.007 
14.  Barbato E, Carrié D, Dardas P, et al. European expert consensus on rotational atherectomy. 
EuroIntervention. Published online 2015. doi:10.4244/EIJV11I1A6 
15.  Wong ND, Kouwabunpat D, Vo AN, et al. Coronary calcium and atherosclerosis by ultrafast computed 
tomography in asymptomatic men and women: Relation to age and risk factors. Am Heart J. Published 
online 1994. doi:10.1016/0002-8703(94)90133-3 
16.  Goel M, Wong ND, Eisenberg H, Hagar J, Kelly K, Tobis JM. Risk factor correlates of coronary 
calcium as evaluated by ultrafast computed tomography. Am J Cardiol. Published online 1992. 
doi:10.1016/0002-9149(92)90346-Z 
17.  M.V. M, M. T, G.S. M, A. M, G.W. S, P. G. Coronary artery calcification: Pathogenesis and prognostic 
implications. J Am Coll Cardiol. Published online 2014. 
18.  Bild DE, Detrano R, Peterson D, et al. Ethnic differences in coronary calcification: The Multi-Ethnic 
Study of Atherosclerosis (MESA). In: Circulation. ; 2005. doi:10.1161/01.CIR.0000157730.94423.4B 
19.  Abedin M, Tintut Y, Demer LL. Vascular calcification: Mechanisms and clinical ramifications. 
Arterioscler Thromb Vasc Biol. Published online 2004. doi:10.1161/01.ATV.0000133194.94939.42 
20.  Demer LL, Tintut Y. Vascular calcification: Pathobiology of a multifaceted disease. Circulation. 
Published online 2008. doi:10.1161/CIRCULATIONAHA.107.743161 
21.  Wang X, Matsumura M, Mintz GS, et al. In Vivo Calcium Detection by Comparing Optical Coherence 
Tomography, Intravascular Ultrasound, and Angiography. JACC Cardiovasc Imaging. Published 
online 2017. doi:10.1016/j.jcmg.2017.05.014 
22.  Vavuranakis M, Toutouzas K, Stefanadis C, Chrisohou C, Markou D, Toutouzas P. Stent deployment 
in calcified lesions: Can we overcome calcific restraint with high-pressure balloon inflations? Catheter 
Cardiovasc Interv. Published online 2001. doi:10.1002/1522-726X(200102)52:2<164::AID-
CCD1041>3.0.CO;2-S 
23.  Kume T, Okura H, Kawamoto T, et al. Assessment of the coronary calcification by optical coherence 
tomography. EuroIntervention. Published online 2011. doi:10.4244/EIJV6I6A130 
24.  Tomey MI, Kini AS, Sharma SK. Current status of rotational atherectomy. JACC Cardiovasc Interv. 
Published online 2014. doi:10.1016/j.jcin.2013.12.196 

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25.  Tamura H, Miyauchi K, Dohi T, et al. Comparison of clinical and angiographic outcomes after bare 
metal stents and drug-eluting stents following rotational atherectomy. Int Heart J. Published online 
2016. doi:10.1536/ihj.15-222 
26.  De Waha S, Allali A, Büttner HJ, et al. Rotational atherectomy before paclitaxel-eluting stent 
implantation in complex calcified coronary lesions: Two-year clinical outcome of the randomized 
ROTAXUS trial. Catheter Cardiovasc Interv. Published online 2016. doi:10.1002/ccd.26290 
27.  Kawamoto H, Latib A, Ruparelia N, et al. Planned versus provisional rotational atherectomy for severe 
calcified coronary lesions: Insights From the ROTATE multi-center registry. Catheter Cardiovasc 
Interv. Published online 2016. doi:10.1002/ccd.26411 
28.  Kovach JA, Mintz GS, Pichard AD, et al. Sequential intravascular ultrasound of the mechanisms of 
rotational atherectomy and adjunct balloon angioplasty. J Am Coll Cardiol. Published online 1993. 
doi:10.1016/0735-1097(93)90412-T 
29.  Kotowycz MA, Khan SQ, Freixa X, et al. Rotational atherectomy through the radial artery is associated 
with similar procedural success when compared with the transfemoral route. Coron Artery Dis. 
Published online 2015. doi:10.1097/MCA.0000000000000198 
30.  Watt J, Oldroyd KG. Radial versus femoral approach for high-speed rotational atherectomy. Catheter 
Cardiovasc Interv. Published online 2009. doi:10.1002/ccd.22066 
31.  Gupta T, Weinreich M, Greenberg M, Colombo A, Latib A. Rotational atherectomy: A contemporary 
appraisal. Interv Cardiol Rev. Published online 2019. doi:10.15420/icr.2019.17.R1 
 
 
 
 
 
 
 
 
 
 

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15. Appendix  
15.1 Appendix 1: Contemporary data on RA-related complication rates 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

40 
 
Version 3 dated 17/01/2021 
15.2 Appendix 2: Definition and breakdown of RA-related complications 
Paper 
Study 
Modality 
Definition 
Outcomes in 
RA 
Safian et. al 
CARAT trial 
CCI 2001 
Prospective, 
randomised, 
multicenter  
RA (large vs 
small burr) 
Any of  
(i) severe 
dissection  
(ii) no reflow 
(iii) side branch 
occlusion 
Total 12.1%; 
severe 
dissection 6.3%, 
no reflow 
(2.3%), 
sidebranch 
occlusion 
(3.5%) 
 
Breakdown by 
burr size: large 
(12.7%) vs 
small (5.1%), p 
< 0.05  
Abdel-Wahab 
et. al 
PREPARE 
CALC trial 
CCI 2018 
Prospective, 
randomised, 
multicenter  
RA vs 
modified 
balloon 
(MB) 
Any of  
(i) large 
dissection 
(>5mm) 
(ii) perforations 
(iii) no/slow 
reflow (iv) side 
branch occlusion 
Large dissection 
(3%), 
Perforation 
(4%), No/slow 
reflow (2%), 
side branch 
occlusion (6%) 
Lee et. al AJC 
2017 
Retrospective, 
single center  
RA vs OA 
Any of  
(i) perforation 
(ii) dissection 
leading to less 
than TIMI 3 flow 
(iii) no reflow 
Perforation/ 
dissection (0%), 
no- reflow (7%) 
Chen et. al. J 
Interven 
Cardiol 2018 
Retrospective, 
single center 
RA of main 
vessel (MV) 
vs side 
branch +/- 
main vessel 
(SB-MV) 
Any of 
(i) No flow 
(ii) SB 
perforation 
(iii) Wire 
transection 
No flow in SB 
(4.2%) vs SB-
MV (2.9%), 
perforation in 
SB (6.3%) vs 
SB-MV (0.8%), 
wire transection 
SB (0%) vs SB-
MV (0.8%) 
 
 
 

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Version 3 dated 17/01/2021 
Breakdown by each complication:  
(i) 
Severe dissection: 1.7 – 5.9% 
a. Lee et. al AJC 2017: any dissection that resulted in < TIMI 3 flow 
b. Safian et. al CARAT trial 2001: any dissection that requires stenting 
c. Abdel-Wahab et al. PREPARE-CALC 2018: large dissection > 5mm 
d. Ali et. al DISRUPT CAD II 2019: any dissection Type D-F that impaired flow 
e. NHLBI (based on depth and breadth of dissection + presence of intimal flap) 
 
(ii) 
Slow flow/ no reflow: 2.5% 
(iii) 
Perforation: 2% 
a. All papers did not define/ classify perforation type. They included all types of perforation in 
analysis for complications 
 
 
 
 
 
 
 
 

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Version 3 dated 17/01/2021 
15.3 Appendix 3: List of study sites/ institutions involved in ROVUS Asia Registry 
Country 
Hospital/Institutions 
PI name  
Last Name  
PI E-mail 
Singapore 
National Heart Centre 
Singapore (Co-PI) 
Khung Keong 
Yeo 
yeo.khung.keong@singhealth.com.sg 
 
Tan Tock Seng 
Hospital 
Deanna 
Khoo 
deanna_zl_khoo@ttsh.com.sg 
National University 
Hospital 
Hui Wen 
Sim 
hui_wen_sim@nuhs.edu.sg 
Japan 
Kokura Memorial 
Hospital (Co-PI) 
Kuramitsu 
Shoichi 
kuramitsu@circulation.jp 
Sapporo 
Cardiovascular Clinic 
Kashima 
Yoshifumi 
rotamonster@gmail.com 
Sugie 
Takuro 
t.sugie@scvc.jp 
Sendai Kousei 
Hospital 
Horie 
Kazunori 
horihori1015@gmail.com  
Vietnam 
Bach Mai Hospital 
Ngoc Quang 
Nguyen 
quangtm@gmail.com 
Cho Ray University 
Hospital 
Minh Hung 
Ngo 
drngominhhung@gmail.com 
Ich Trung 
Ly 
lyichtrung@yahoo.com 
Thailand 
Central Chest Hospital 
Wirash 
Kehasukcharoen 
kwirash@yahoo.com 
King Chulalongkorn 
Hospital 
Wacin 
Buddhari 
wacin_buddhari@yahoo.com 
Malaysia 
Serdang Hospital 
Dato Kahar 
Abdul Ghapar 
drabdkahar@moh.gov.my 
Cardiac Vascular 
Sentral Kuala Lumpur 
Dato Dr 
Tamil 
Selvan 
selvan63@gmail.com