Supplemental material

Search strategy for PubMed, Embase and CENTRAL

1) cFFR studiesPubMed: 215((((contrast medium Fractional Flow Reserve[Title/Abstract]) OR (contrast Fractional Flow Reserve[Title/Abstract]) OR contrast-* Fractional Flow Reserve[Title/Abstract]) OR contrast medium induced Pd/Pa[Title/Abstract]) OR cFFR[Title/Abstract])) AND ((("Fractional Flow Reserve, Myocardial"[Mesh]) OR FFR[Title/Abstract]) OR fractional flow reserve[Title/Abstract]))

Embase: 21No. Query Results Results Date #8. #5 AND #6 AND ([article]/lim OR [article in press]/lim) 21 7 Jun 2019#7. #5 AND #6 56 7 Jun 2019#6. #3 OR #4 64 7 Jun 2019#5. #1 OR #2 7281 7 Jun 2019#4. 'contrast induced fractional flow reserve':ab,ti OR 'cffr':ab,ti 64 7 Jun 2019#3. 'contrast induced fractional flow reserve' 2 7 Jun 2019#2. 'fractional flow reserve':ab,ti OR 'ffr':ab,ti 5874 7 Jun 2019#1. 'fractional flow reserve'/exp 5911 7 Jun 2019

CENTRAL: 13#1 MeSH descriptor: [Fractional Flow Reserve, Myocardial] explode all trees 91#2 fractional flow reserve:ti,ab,kw or FFR:ti,ab,kw (Word variations have been searched)#3 #1 or #2 510 #4 instantaneous wave-free ratio:ti,ab,kw or cFFR:ti,ab,kw (Word variations have been searched) 13#5 #3 and #4 13

2) QFR studiesPubMed: 28((((FFR[Title/Abstract]) OR fractional flow reserve[Title/Abstract]) OR "Fractional Flow Reserve, Myocardial"[Mesh])) AND ((QFR[Title/Abstract]) OR quantitative flow ratio[Title/Abstract])

Embase: 71No. Query Results Results Date #5. #1 AND #4 71 7 Jun 2019#4. #2 OR #3 7281 7 Jun 2019#3. 'fractional flow reserve':ab,ti OR 'ffr':ab,ti 5874 7 Jun 2019#2. 'fractional flow reserve'/exp 5911 7 Jun 2019#1. 'quantitative flow ratio':ab,ti OR 'qfr':ab,ti 128 7 Jun 2019

CENTRAL: 17#1 MeSH descriptor: [Fractional Flow Reserve, Myocardial] explode all trees 510#2 fractional flow reserve:ti,ab,kw or FFR:ti,ab,kw (Word variations have been searched)#3 #1 or #2 510

#4 quantitative flow ratio:ti,ab,kw or QFR:ti,ab,kw (Word variations have been searched) 885#5 #3 and #4 1

Table S1 Inclusion and exclusion criteria of studies

Study (First

author)

Inclusion criteria Exclusion criteria

Instantaneous flow ratio (cFFR)

Leone

MEMENTO

coronary artery stenoses with

FFR measurement

recent myocardial infarction, severe valvular

heart disease, acute heart failure, or advanced

renal failure

Johnson Patients with the first lesion

studied using FFR, including

nonculprit lesions of an acute

infarction

Not first lesion studied using FFR. Culprit lesions

for an acute infarction. Previous CABG, known

severe cardiomyopathy (left ventricular ejection

fraction <30%) or left ventricular hypertrophy

(septal wall thickness >13 mm), contraindication

to adenosine, or renal insufficiency

Topcu patients with 50–70% stenoses

of at least one major epicardial

artery by visual assessment

saphenous venous graft stenosis, recent (< 7

days) acute coronary syndrome, left main

coronary stenosis, tandem lesions in epicardial

artery, baseline Pd/Pa ≤ 0.80 and absolute

contraindications to adenosine.

Kanaji intermediate lesions undergoing

diagnostic cardiac

catheterization for suspected

coronary artery disease

a history of coronary artery bypass surgery,

extremely tortuous coronary arteries, severely

calcified arteries, acute coronary syndrome, a

history of myocardial infarction, occluded

coronary arteries, left main disease, coronary

ostial stenosis, congestive heart failure,

significant arrhythmia, renal insufficiency

(creatinine N1.5 mg/dL), or an absolute

contraindication to adenosin

Vankwy mild or moderate coronary

stenosis undergoing coronary

angiography

Patients with myocardial infarction

Cerrato Left main and right coronary

ostium stenoses, severe renal

failure (Cockroft-Gault

glomerular filtration rate

30 mL/min), recent myocardial

infarction (within one week) or

prior

myocardial infarction in the area

of myocardium subtended by

target

Left main and right coronary ostium stenoses,

severe renal failure (Cockroft-Gault glomerular

filtration rate 30 mL/min), recent myocardial

infarction (within one week) or prior myocardial

infarction in the area of myocardium subtended

by target

vessel, severe valvular heart disease, acute or

chronic decompensated heart failure and a known

history of Asthma or COPD with severe

obstructive component

Shiode patients with mild or moderate

coronary

stenosis undergoing coronary

angiography

unclear

Quantitative flow ratio (QFR)

FAVOR

Pilot

Patients ≥18 years of age with

stable angina and indication for

invasive coronary angiography

and FFR assessment

Contraindications to adenosine or adenosine

triphosphate administration, ostial left main or

ostial right coronary artery lesion and prior

CABG of the interrogated vessels

FAVOR Ⅱ

CHINA

Adults with suspected or known

CAD who were admitted for

coronary angiography

MI within 72 h of coronary angiography, severe

heart failure, allergy to the contrast agent or

adenosine, serum creatinine >150 μmol/l or

glomerular filtration rate <45 ml/kg/1.73 m2,

ineligible for diagnostic intervention or FFR, had

factors that might affect angiographic image

quality

Yazaki Patients who underwent

coronary angiography and FFR

measurements

Lack of 2 optimal angiographic projections at

least 25° apart, overlapping interrogated vessels

with too much shortening without preferred

references in proximal or distal vessels,

insufficient injected contrast for QCA analysis,

and location of the target lesion at the ostium of

the left or right coronary artery

Emori

(Coron

Artery Dis)

Patients who underwent

angiography, cFFR and FFR

Incomplete coronary angiography, ostial lesions

in coronary arteries, collateral donor arteries,

CABG, chronic atrial fibrillation

Emori (Circ Consecutive series of prior- Incomplete angiographic results, ostial lesions,

J) AMI-related and non-related

coronary arteries

collateral donor arteries, CABG, chronic atrial

fibrillation, prior-MI in non-target coronary

arteries

Mejia-

Renteria

Patients with CAD who

underwent comprehensive

physiological assessment with

FFR and IMR

Ostial left main and ostial right coronary artery

target lesions, previous CABG in target vessel,

poor angiography image quality, too much

overlap or sever tortuosity of target senoses, and

no availability of the raw intracoronary

physiology studies

Spitaleri Patients ≥18 years old who

presented with STEMI within 12

hours after symptom onset and

non-infarct related stenosis

≥50%

None

FAVOR Ⅱ

Europe-

Japan

Patients with stable angina or

NSTEMI undergoing coronary

angiography and FFR

measurement

AMI within 72 hours, severe asthma or severe

COPD, allergy to contrast media or adenosine,

and atrial fibrillation

WIFI Ⅱ Patients with stenosis referred

for invasive coronary

angiography

<2 projections with visible stenosis, stenosis in

the ostium of the right coronary artery or left

main coronary artery, no administration of

intracoronary nitrates, pressure wire position not

documented angiographically

Tie 1) documentation of the exact

wire-based FFR values, 2)

availability of two angiogram

acquisitions of the interrogated

vessel, 3) an angle ≥25° between

the two angiogram acquisitions

of one vessel and 4)

perpendicularity of both

acquisitions towards the

interrogated vessel

1) no documented nitroglycerine administration

prior to the recording of acquisitions, 2) image

acquisition speed of b10 frames/s, 3) prior CABG

on the interrogated vessel 4) true bifurcation

lesion (1-1-1 according to Medina classification),

5) ostial left main or ostial right coronary artery

lesion,6) retrograde filling of the interrogated

vessel, 7) hyperdynamic heart."

Kołtowski patient with stable coronary

disease undergoing FFR

examination

(1) diameter stenosis of < 30% or > 90%; (2)

vessels of < 2 mm of reference diameter; (3)

bifurcation lesions with side branch of > 2 mm;

(4) lack of two optimal angiographic projections

at

least 25° apart; (5) location of the target lesion at

the ostium of the left main coronary artery or the

right coronary artery;(6) bypass graft supplying

the target vessel; (7) overlapping vessels at target

segment; (8) too much shortening; (9) too short

recordings of projections, which did not allow to

determine the end-diastolic phase, (10)

hyperemia not induced by intravenous adenosine

infusion.

Hwang Patients with acute myocardial

infarction

AMI who underwent clinically

indicated physiologic

assessment for nonculprit

stenosis with visual stenosis of

40% to 80%

limited coronary angiographic image quality for

QFR analysis (calibration failure, ostial disease,

insufficient projections, tortuous vessels,

overlapping of vessels, or poor contrast filling)

Stähli Patients with native de novo

coronary lesions

CABG to interrogated vessels, suboptimal

documentation of FFR-measurements,

suboptimal angiographic image quality, lack of at

least 2 projections ≥25° apart, vessel overlap or

shortening, ostial lesions, suboptimal contrast

filling, and other technical issues impeding high-

quality QFR analysis.

CABG: coronary artery bypass graft, FFR: fractional flow reserve, AMI: acute myocardial infarction,

STEMI: ST-segment elevation myocardial infarction, CTO: chronic total occlusion, LVEF: left

ventricle ejection fraction, NSTEMI: non-ST-segment elevation myocardial infarction, PCI:

percutaneous coronary intervention, NYHA: New York Heart Association, LBBB: left bundle branch

block, ACS: acute coronary syndrome, CHF: congestive heart failure, CAD: coronary artery disease,

AS: aortic stenosis, DSE: dobutamine stress echocardiography, QCA: quantitative coronary

angiography, IMR: index of microcirculatory resistance, COPD: chronic obstructive pulmonary

disease.

Table S2 Sensitivity analysis of cFFR sensitivity

In every line is indicated the result of the meta-analysis leaving out that study

Study Sensitivity LCI UCI Heterogeneity(I2)

Cerrato 0.798 0.826 0.851 78.40%

Vankwy 0.804 0.831 0.856 60.20%

Shiode 0.798 0.826 0.851 77.30%

Kanaji iFR 0.802 0.829 0.854 81.20%

MEMENTO-FFR 0.769 0.805 0.838 76.30%

Topcu 0.804 0.83 0.855 81.50%

Johnson 0.853 0.885 0.911 0.00%

LCI: lower confidence interval; UCI: upper confidence interval

Table S3 Sensitivity analysis of cFFR specificity

In every line is indicated the result of the meta-analysis leaving out that study

Study Specificity LCI UCI heterogeneity(I2)

Cerrato 0.904 0.92 0.934 54.20%

Vankwy 0.906 0.922 0.936 60.20%

Shiode 0.905 0.921 0.936 77.30%

Kanaji iFR 0.904 0.92 0.935 56.40%

MEMENTO-FFR 0.925 0.946 0.962 0.00%

Topcu 0.906 0.922 0.936 60.50%

Johnson 0.889 0.91 0.928 13.20%

LCI: lower confidence interval; UCI: upper confidence interval

Table S4 Sensitivity analysis of QFR sensitivity

In every line is indicated the result of the meta-analysis leaving out that study

Study Sensitivity LCI UCI Heterogeneity(I2)

Yazaki 0.845 0.867 0.887 80.94%

WIFI Ⅱ 0.857 0.879 0.899 81.16%

Ties 0.851 0.872 0.892 83.31%

Stahli 0.858 0.88 0.9 79.15%

Spitaleri 0.845 0.867 0.887 81.80%

Mejia-Renteria 0.841 0.865 0.886 81.28%

Koltowski 0.849 0.872 0.893 78.98%

Hwang 0.836 0.86 0.881 84.96%

FAVOR Pilot 0.85 0.872 0.891 81.98%

FAVOR II CHINA 0.835 0.859 0.881 76.35%

FAVOR Europe-JapanⅡ 0.846 0.869 0.889 80.07%

Emori (Coron Artery Dis) 0.838 0.861 0.882 84.66%

Emori (Circ J) 0.845 0.867 0.887 75.21%

LCI: lower confidence interval; UCI: upper confidence interval

Table S5 Sensitivity analysis of QFR specificity

In every line is indicated the result of the meta-analysis leaving out that study

Study Specificity LCI UCI Heterogeneity(I2)

Yazaki 0.894 0.908 0.921 78.89%

WIFI Ⅱ 0.896 0.91 0.923 76.05%

Ties 0.89 0.904 0.917 71.00%

Stahli 0.87 0.887 0.903 19.40%

Spitaleri 0.892 0.906 0.919 75.14%

Mejia-Renteria 0.896 0.911 0.923 76.30%

Koltowski 0.897 0.911 0.924 78.32%

Hwang 0.89 0.908 0.921 77.21%

FAVOR Pilot 0.892 0.907 0.919 78.21%

FAVOR II CHINA 0.891 0.905 0.919 74.80%

FAVOR Europe-JapanⅡ 0.897 0.911 0.924 79.13%

Emori (Coron Artery Dis) 0.893 0.907 0.92 71.39%

Emori (Circ J) 0.895 0.909 0.922 76.30%

LCI: lower confidence interval; UCI: upper confidence interval

Figure S1: Meta-regression analysis of cFFR studies

Figure S2: Meta-regression analysis of QFR studies

Figure S3: Methodological quality of included studies of cFFR

Figure S4: Methodological quality of included studies of quantitative flow ratio

Figure S5: Deek’s funnel plot for cFFR studies

Figure S6: Deek’s funnel plot for QFR studies