A Prospective Study of Fractional Flow Reserve Assessment of Intermediate Coronary Stenoses in Severe Aortic Stenosis
Phase: NA
Conditions: Coronary Artery Stenoses, Aortic Stenosis
Sponsor: The Cleveland Clinic

Version 5/8/2017 
Clinical Investigation Plan 
 
A Prospective Study of Fractional Flow Reserve Assessment of 
Intermediate Coronary Stenoses in Severe Aortic Stenosis 
 
Study Title 
A Prospective Study of Fractional Flow Reserve Assessment of 
Intermediate Coronary Stenoses in Severe Aortic Stenosis 
Study Site 
Cleveland Clinic Heart & Vascular Institute 
Study Design 
Prospective, single-center. We anticipate enrolling 50 patients. Fractional 
flow reserve (iFR and FFR) assessment will be performed on all 
intermediate coronary stenoses using standard practice, immediately 
before TAVR (at the time of the procedure). Maximal hyperemia will be 
achieved utilizing intravenous adenosine. Immediately post-TAVR, the 
same lesions will be reassessed. We will compare pre- and post-TAVR 
iFR and FFR values, and assess short-term outcomes. 
Study Objective 
The purpose of the study is to determine whether iFR assessment gives a 
valid assessment of coronary hemodynamics in patients with severe aortic 
stenosis. 
 
Several factors confound the interpretation of fractional flow reserve (FFR) 
in patients with severe aortic stenosis (AS) and intermediate severity 
coronary stenoses, and the widely accepted cut-off value of 0.80 may not 
be applicable to this patient population. Coronary flow reserve is known to 
be attenuated under conditions of left ventricular hypertrophy and severe 
AS, with one study showing improvement in coronary flow reserve after 
aortic valve replacement. Left ventricular hypertrophy produces fixed 
resistance secondary to external compression of the coronary 
microcirculation. This potentially results in failure to achieve maximal 
hyperemia with adenosine and can lead to false negative FFR results. 
Neurohormonal influences in aortic stenosis can further attenuate 
vasodilator response and potentially result in false negative FFR values. 
Both of these conditions result in the potential deferral of lesions which 
may have been hemodynamically significant in the absence of severe AS. 
At present, there are no studies which have demonstrated validity of 
iFR/FFR measurement in patients with severe AS. Here, we propose a 
prospective study of iFR/FFR in patients with AS and indeterminate 
coronary lesions undergoing TAVR to understand the hemodynamic 
consequences of AS on iFR/FFR. We hypothesize that iFR/FFR values 
will be consistently and significantly higher pre-TAVR in comparison with 
post-TAVR for the same lesions. 
Covariates of 
Interest 
Demographics 
 
Age 
 
Sex 
Comorbid conditions 

Version 5/8/2017 
 
Diabetes 
 
Hypertension 
 
Hyperlipidemia 
 
Kidney disease status 
 
Previous PCI 
 
Previous myocardial infarction 
 
Stress test information 
Current medications 
Echocardiography data 
 
Valve area 
 
Aortic valve gradients 
 
Dimensionless index of aortic valve 
 
Stroke volume indexed 
 
Ejection fraction 
 
Wall motion abnormalities 
Frailty score 
Angiographic Characterisitcs 
 
Lesion location 
 
Lesion severity 
 
Location 
 
Presence and degree of calcification 
 
Myocardial jeopardy score 
 
Syntax score 
IVUS characteristics (if available) 
Fractional flow reserve characteristics 
 
FFR value pre- and post-TAVR 
 
Distal pressure & proximal pressure 
 
Adenosine dose used to achieve hyperemia 
 
Route of adenosine administration 
 
Wave form 
 
Coronary diastolic pressures differences during hyperemia 
Enrollment 
A maximum of 20-50 patients will be enrolled in the registry. 
Clinical Sites 
Cleveland Clinic Heart & Vascular Institute 
Study Duration 
Anticipated enrollment period: Q4 2016 and Q1 2017 
Inclusion Criteria 
Consecutive stable patients with at least one intermediate coronary 
stenosis and severe AS undergoing TAVR will be enrolled and followed in 
our registry. 
 
Severe aortic stenosis is defined by: 
 
Presence of AVA < 1 cm^2 
 
Peak velocity > 4 m/s 

Version 5/8/2017 
 
Mean gradient > 40 mmHg 
 
Dimensionless index < 0.25 
 
Low flow, low gradient, severe AS (increase in LVOT VTI of at 
least 20% with AVA <1 cm^2) 
 
Intermediate severity coronary stenosis is defined by percent stenosis 40-
70%. 
Exclusion 
Criteria 
 
Contraindication to adenosine. 
 
Presence of cardiogenic shock. 
 
Presence of acute coronary syndrome. 
Principal 
Investigator 
Samir R. Kapadia MD 
Director, Sones Cardiac Catheterization Laboratories 
Cleveland Clinic, Heart & Vascular Institute 
Cleveland, OH, USA 
 
 
References: 
1. http://content.onlinejacc.org/article.aspx?articleid=1126804 
2. http://www.nature.com/nrcardio/journal/v13/n5/full/nrcardio.2016.9.html?WT.feed_name
=subjects_interventional-cardiology