Supplementary Methods
The clinical pertinence of integration of hyperemic flow and CFR was evaluated by the
continuous net reclassification improvement (NRI), integral discrimination improvement (IDI)
and relative IDI (rIDI).1,2 The NRI and IDI were calculated by analyzing the differences in
patients’ individual estimated probability of MACE after addition of a single diagnostic test
(hAPV, FFR, HSR, or MPS) to a reference model containing CFR. The NRI was calculated
separately for those who did or did not develop MACE, and indicates the percentage of
patients in whom the predicted probability for MACE improved after addition of the
diagnostic test to CFR. The IDI considers the change in predicted probabilities as a
continuous variable and represents the average improvement in predicted probability after
addition of the diagnostic test. The rIDI reflects the percent change in the predicted
probability after addition of the diagnostic test relative to the predicted probability of the
model with CFR alone.
References
1.
Pencina MJ, D'Agostino RB, Sr., D'Agostino RB, Jr., Vasan RS. Evaluating the added
predictive ability of a new marker: from area under the ROC curve to reclassification and
beyond. Statistics in medicine 2008; 27(2): 157-72; discussion 207-12.
2.
Pencina MJ, D'Agostino RB, Sr., Steyerberg EW. Extensions of net reclassification
improvement calculations to measure usefulness of new biomarkers. Statistics in medicine
2011; 30(1): 11-21.
Supplementary Table 1. Baseline characteristics of the study population in which
revascularization was deferred
Number of patients
Demographics
Age, yrs
Male sex
Coronary risk factors
Hypertension
Hyperlipidemia
Positive family history
Cigarette smoking
Diabetes mellitus
Prior myocardial infarction
Prior coronary intervention
Medication at hospital admission
Beta-blocker
Nitrates
Calcium antagonists
ACE-inhibitors
Lipid-lowering drugs
Aspirin
ACE: Angiotensin-converting enzyme
154
61±11
110 (71)
60 (39)
89 (58)
76 (49)
48 (31)
24 (16)
57 (37)
34 (22)
120 (78)
110 (71)
101 (66)
28 (18)
87 (56)
149 (97)
Supplementary Table 2. Net reclassification improvement (NRI), integrated discrimination
improvement (IDI), and relative IDI (rIDI) for prediction of long-term major adverse cardiac
events by addition of FFR, HSR, and MPS to a baseline model containing CFR.
Parameter
Fractional flow reserve
Hyperemic stenosis
resistance index
Myocardial perfusion
scintigraphy
SE: standard error
Net reclassification
improvement
NRI (SE)
p-value
0.14 (0.17)
0.40
(Relative) integrated discrimination
improvement
IDI (SE)
rIDI
p-value
0.006 (0.007)
10.7%
0.41
0.23 (0.17)
0.17
0.02 (0.013)
37.3%
0.11
0.05 (0.17)
0.77
0.001 (0.003)
2.0%
0.73
Supplemental Figure 1. Distribution of FFR values across the deferred study population. The
deferred study population showed a unimodal distribution, resembling a clinical population
that is routinely referred for FFR-measurements in contemporary clinical practice.
Supplemental Figure 2. Distribution of hyperemic average peak flow velocity (hAPV)
values within the studied reference coronary arteries. Dashed red line indicates the
threshold for severely reduced hAPV (<26.1)