Comparison of Orbital Versus Rotational Atherectomy Effects On Coronary Microcirculation in Percutaneous Coronary Intervention (PCI)
Phase: NA
Conditions: Coronary Artery Disease (CAD)
Sponsor: Columbia University

 
 
 
 
 
 
 
 
 
Comparison of Orbital Versus Rotational Atherectomy Effects 
On Coronary Microcirculation in Percutaneous Coronary 
Intervention (PCI) 
 
 
ClinicalTrials.gov ID: NCT03021577 
 
IRB approved on April 15, 2020 
 
 

Comparison of Orbital versus Rotational Atherectomy  Effects 
On Coronary Microcirculation in Percutaneous Coronary 
Intervention 
Columbia University Medical Center and Cardiovascular Research 
Foundation 
 
Principal Investigator:  Ziad Ali, MD 
 
Scientific basis/Rationale: The presence of heavily calcified coronary lesions 
necessitates the use of ablative devices that aid in successful percutaneous coronary 
intervention (PCI). However, atherectomy devices generate microparticles that 
embolize to the distal coronary microcirculation and may compromise myocardial 
tissue perfusion. We hypothesize that the orbital atherectomy system (OAS), a newer 
generation atherectomy device, reduces the incidence of microcirculatory compromise 
as compared to older generation rotational atherectomy (RA) due to differences in the 
mechanism of athero-ablation.  
 
Two mechanisms that deserve particular attention are the eccentric mounting of the 
OAS crown and the higher flow rates on the vasodilator flush. Firstly, as opposed to 
rotational atherectomy where the larger, centrally mounted burr may cause obstruction 
of flow during the atherectomy, the smaller eccentrically mounted crown in OAS allows 
continuous perfusion during both atherectomy as well as rest periods. Second, both 
during rest and atherectomy, the flow rates of vasodilatory flush is higher in OAS 
compared to RA. Combined, these differences in coronary and vasodilator flush flow 
could lead to improved perfusion of the distal circulation, particularly during the 
atherectomy runs when risk of embolization is highest.  
 
The loss of microcirculatory function can be transient, with partial or complete 
restoration of microcirculatory blood flow, or permanent. As shown in studies of 
patients with acute coronary syndromes, the loss of microcirculatory function is a 
critical and independent predictor of myocardial recovery and adverse outcomes.1 The 
putative protective effects of OAS on coronary microvasculature may therefore be of 
major clinical significance and impact. 
 
Central hypothesis: OAS is associated with lower loss of coronary microcirculatory 
function as compared to RA. 
 
Primary Objectives: To compare the effect of OAS versus RA on coronary 
microcirculatory function as measured by saline transit time under basal and 
hyperemic conditions in patients with clinical indication for PCI in whom atherectomy 
for optimal PCI is clinically warranted.  
 
Fractional flow reserve (FFR), coronary flow reserve (CFR) and the index of 
microcirculatory resistance (IMR) will be the primary physiological indices recorded  
 
Exploratory Objectives: To compare the incidence of peri-PCI myonecrosis with OAS 
versus RA, as assessed by measurement of CK-MB and Troponin I and in a subgroup 
of 20 myocardial edema and late gadolinium enhancement on cardiac MRI.. 
 
Rationale: Lower incidence of microvascular compromise with OAS may be protective 
against peri-atherectomy microvascular “plugging” and loss of tissue perfusion, and 
thereby may result in a reduction in peri-PCI myocardial necrosis, potentially protecting 
left ventricular function. In patients undergoing elective PCI, IMR has been shown to 

independently predict PCI-related microvascular damage and peri-procedural 
myonecrosis. 
 
Trial Design:  Randomized, prospective, single-center, investigator initiated, study at 
Columbia University Medical Center (CUMC). 
 
Sample Size: 20   
 
 
Inclusion Criteria:  
1) Age ≥ 18 years 
2) Patient with an indication for PCI including: 
i) 
Angina (stable or unstable),  
ii) Silent ischemia (a visually estimated target lesion diameter stenosis of 
≥70%, a positive non-invasive stress test, or FFR ≤0.80 must be present),  
iii) NSTEMI 
3)    Patients will undergo cardiac catheterization and possible or definite PCI with 
intent to stent using any non-investigational metallic drug-eluting stent (DES) 
4)   Signed written informed consent  
5)   Heavily calcified (severe)lesions necessitating atherectomy. 
 
Angiographic inclusion criteria: 
1) 
The target lesion must be located in a native coronary artery with visually  
            estimated reference vessel diameter of ≥2.25 mm to ≤4.00 mm. 
2) 
Lesion length between 20 mm and 50mm 
 
General Exclusion Criteria: 
1) 
Estimated creatinine clearance <30 ml/min using Cockcroft-Gault equation,  
            unless the patient is on dialysis;  
2) 
STEMI within 24 hours of initial time of presentation to the first treating hospital,  
            whether at a transfer facility or the study hospital. 
3) 
PCI within 24 hours preceding the study procedure. 
4) 
Cardiogenic shock (defined as persistent hypotension (systolic blood pressure  
            <90 mm/Hg for more than 30 minutes) or requiring pressors or hemodynamic  
            support, including IABP, at time of procedure. 
5) 
Mobitz II second degree or complete  heart block 
6) 
Malignant ventricular arrhythmias requiring treatment 
7) 
Pulmonary edema defined as patient with shortness of breath, evidence of  
            volume overload on physical exam, and crepitations on physical exam (>1/3 of  
            lungs) or radiographic interstitial or alveolar pulmonary edema 
8) 
Subject is intubated. 
9) 
Known LVEF <35%. 
10) 
Severe valvular disease (e.g. severe mitral regurgitation or severe aortic  
            stenosis) 
11) 
Patient is participating in any other investigational drug or device clinical trial  
            that has not reached its primary endpoint.  
12) 
Women who are pregnant or breastfeeding (women of child-bearing potential  
            must have a negative pregnancy test within one week before treatment). 
 
Angiographic Exclusion Criteria: 
1) Lesion length <20mm 
2) Study target lesion in a bypass graft  
3) Ostial RCA study target lesion 
4) Chronic total occlusion  (TIMI flow 0/1) study target lesion 
5) Bifurcation study lesion with a planned dual stent strategy 
6) In-stent restenosis study target lesion 

Procedures:  
Physiological indices:  Subjects will be randomized on a 1:1 basis to OAS versus 
RA.  In both groups, we will perform sequential physiological interrogation of the 
coronary vasculature before and immediately after atherectomy and at the end of PCI, 
utilizing a direct and robust assessment of microvascular function. This will be 
achieved by measurement of the mean transit time (Tmn) of saline using a single 
pressure-temperature sensor-tipped coronary wire (CertusTM guidewire, St Jude 
Medical, St Paul, Minnesota). The following parameters will be assessed: 
 
(1) Total coronary flow (1/Tmn) 
With the pressure sensor of the coronary wire acting also as a distal thermistor and 
the shaft of the wire serving as a proximal thermistor, the mean transit time of saline 
injected down a coronary artery can be derived from a coronary thermodilution curve. 
De Bruyne, Pijls and colleagues found a strong correlation between the inverse of Tmn 
and absolute flow2. 
 
(2) Microvascular resistance (Pd * Tmn) 
Extrapolating from Ohm’s law, distal coronary pressure (Pd) divided by the inverse of 
the hyperemic mean transit time (a correlate to absolute flow), measured 
simultaneously with the coronary pressure wire, will evaluate microvascular resistance. 
Under peak hyperemia (achieved by intravenous infusion of adenosine at 
140 g/kg/min) this ratio has been called the IMR3. IMR is derived from the assumption 
that at peak hyperemia the variability of resting vascular tone and hemodynamics will 
be eliminated, and the minimum microvascular resistance will be achieved3.  
 
(3) Coronary Wedge Pressure (Pw) 
In addition to the IMR we will assess the coronary wedge pressure, measured by 
trapping the pressure transducer on the pressure wire with a proximally inflated 
balloon. Measurements will be taken immediately following atherectomy and than 
repeated following administration of adenosine and a 3 minute rest period. The 
difference between the pre and post adenosine coronary wedge pressure will be 
indicative of the microcirculatory “plugging” caused by atherectomy.   
In addition, we will measure Tmn both at rest and at peak hyperemia. If the effects of 
OAS on the microvasculature are less than RA and the relatively smaller microparticles 
generated by OAS are more readily “washed out” of the microcirculation with 
adenosine-induced hyperemia, we expect to see a difference between OAS and RA in 
Tmn and Pd * Tmn both with resting and hyperemic (i.e. IMR) indices.  
 
We will also use the data to calculate the coronary flow reserve (CFR) that is an index 
of total blood flow in coronary bed under peak hyperemia relative to rest as described 
previously2.   
 
(4) CFR (Tmn at rest/Tmn at hyperemia) 
 
The indication for PCI will be based on measurement of FFR, the current standard of 
practice, which will be determined as: 
 
(5) FFR (Pd/Pa at hyperemia)   
 
where Pa is the aortic pressure measured by the guiding catheter at peak hyperemia. 
PCI is indicated in stenoses with FFR <0.85.  
 
Tmn under basal condition followed sequentially by IMR, FFR and CFR under maximum 
hyperemia will be measured at 3 separate time points: 1) pre-atherectomy, 2) 
immediately post atherectomy and 3) at the end of the PCI.   

 
Screening 
Procedure 
Post 
Procedure 
Discharge 
Consent 
X 
 
 
 
Medical History 
X 
 
 
 
Randomization 
X 
 
 
 
CK/MB 
 
 
X1 
 
Troponin I 
 
 
X1 
 
Physiological 
Measurements (FFR) 
 
X2 
 
 
X1 4-8 hours post procedure; if positive again at 12-18 hours 
X2 Physiological measurements (Total coronary flow, Microvascular resistance, Coronary 
wedge pressure, Coronary flow reserve and Fractional flow reserve) will be taken before and 
immediately after atherectomy and at the end of PCI) 
 
Sample Size: A clinically important difference would be 20% reduction in IMR in OAS, 
equating to an IMR difference of 7 (SD=8, α =0.05 and power=0.80) and requiring a 
total sample size of 20. 
 
Projected time for completion: 1 year. CUMC has a large volume for PCI with ~ 3000 
number of PCIs per year including ~250 procedures requiring atherectomy.   
 
Significance of the results: If OAS is shown to cause lower disruption and loss of 
coronary microcirculatory function, the use of this atherectomy device may have 
significant favorable impact on myocardial recovery and function post PCI as 
compared to RA, potentially leading to prevention of major adverse cardiovascular 
events.   
 
 
Preliminary results: 
 
Table 1. Physiological findings* 
 
OAS 
(n=6) 
RA 
(n=4) 
P 
Post-atherectomy 
 
 
Coronary Flow (1/s) 
1.78±.21 
1.41±.62 
0.25 
Index of microcirculatory resistance (a.u) 
21±6 
31±7 
0.04 
Coronary wedge pressure (mmHg) 
21±6 
27±6 
0.15 
± standard deviation; *preliminary nonrandomized data.  
 
Risks: 
The risks associated with this study will involve the risks of inserting wires into the 
coronary arteries and with the administration of adenosine.  The study protocol calls 
for an additional intracoronary wire insertion for physiology measurements.  The risks 
include extra flouroscopy time (approximately 10-20 seconds), extra contrast (less 
than 10 mL), and a <1% risk of coronary artery damage (dissection or perforation).   
Adenosine is used to measure FFR. The most common adverse effects of adenosine 
are headache, facial flushing, bronchospasm, and conduction abnormalities.  
Performance of FFR is generally safe, but does require placement of a wire and 
catheter in the coronary artery which can rarely cause injury to the artery.  
 

There are no risks for an MRI and few, if any, side effects. The test does not use 
radiation, and to date, there have been no documented side effects from the radio and 
magnetic waves it uses. Allergic reactions to the dye are rare.  Individuals with 
claustrophobia may feel uncomfortable in the MRI machine. 
 
Radiation Risk 
A small amount of radiation is needed for this research (about ½ millisievert). The extra 
lifetime risk of dying from cancer due to this radiation may be one in 50,000. The 
chances of a person dying of cancer with no extra radiation exposure are about one in 
4.  At such low radiation exposures, scientists disagree about the amount of risk. These 
estimates are very uncertain. An amount of radiation greater than usual is needed for 
this research. 
  
Benefits: 
Conducting FFR may provide the operator  with additional information about the 
anatomy and physiology of the patients heart and further assistant in the direction of 
their course of treatment.  Future patients will benefit from the knowledge gained from 
conducting this study.  
 
Alternatives 
Patients who do not consent to participate in the research will be treated with 
whichever device the operator prefers (OAS versus  RA) with or without FFR and will 
not undergo FFR.  All other procedures are standard of care.   
 
 
Safety Monitoring Plan 
The PI (Dr. Ali will be responsible for monitoring and patient safety for the full duration 
of the study.  Adverse events will be reviewed and all unanticipated problems will be 
reported to the IRB in accordance with Columbia University Medical Center IRB 
Policies and Procedures. 
 
 
References:   
 
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Camici PG, d'Amati G, Rimoldi O. Coronary microvascular dysfunction: 
mechanisms and functional assessment. Nature reviews Cardiology 2015;12(1):48-
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De Bruyne B, Pijls NH, Smith L, Wievegg M, Heyndrickx GR. Coronary 
thermodilution to assess flow reserve: experimental validation. Circulation 
2001;104(17):2003-6. 
3. 
Fearon WF, Balsam LB, Farouque HM, Caffarelli AD, Robbins RC, Fitzgerald 
PJ, Yock PG, Yeung AC. Novel index for invasively assessing the coronary 
microcirculation. Circulation 2003;107(25):3129-32. 
4. 
Layland J, MacIsaac AI, Burns AT, Somaratne JB, Leitl G, Whitbourn RJ, 
Wilson AM. When collateral supply is accounted for epicardial stenosis does not 
increase 
microvascular 
resistance. 
Circulation 
Cardiovascular 
interventions 
2012;5(1):97-102. 
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De Bruyne B, Fearon WF, Pijls NH, Barbato E, Tonino P, Piroth Z, Jagic N, 
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A, Nuesch E, Juni P, Investigators FT. Fractional flow reserve-guided PCI for stable 
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