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2. Zoghbi WA, Asch FM, Bruce C, et al. Guidelines for the evaluation of
valvular regurgitation after percutaneous valve repair or replacement. J Am
Soc Echocardiogr. 2019;32(4):431–475.
3. Ancona MB, Moroni F, Pagnesi M, et al. Impact of left ventricular outflow
tract calcification on pacemaker implantation after transcatheter aortic valve
implantation with second-generation devices. J Invasive Cardiol. 2020;32(5):
180–185.
4. Bettinger N, Khalique OK, Krepp JM, et al. Practical determination of aortic
valve calcium volume score on contrast-enhanced computed tomography
prior to transcatheter aortic valve replacement and impact on paravalvular
regurgitation: elucidating optimal threshold cutoffs. J Cardiovasc Comput
Tomogr. 2017;11(4):302–308.
as the composite of cardiovascular mortality, MI, and
repeat revascularization (RR). Secondary endpoints
included the individual components of the primary
endpoints.
Patients and lesions were classified according to
the FFRangio-recommended treatment (revascularization or deferral). Cumulative incidence was calculated using the Kaplan-Meier method.
Our cohort included 536 patients with a total of 601
5. Blanke P, Willson AB, Webb JG, et al. Oversizing in transcatheter aortic
valve replacement, a commonly used term but a poorly understood one:
dependency on definition and geometrical measurements. J Cardiovasc Comput Tomogr. 2014;8(1):67–76.
lesions. In 492 of the patients (91.8%) and 552 of the
6. Timofeev RV. Classification and Regression Trees (CART): Theory and Applications. Berlin: Humboldt University; 2004.
(52.0%) in whom revascularization was deferred and
lesions (91.8%), treatment decisions were consistent
with the FFRangio results. There were 256 patients
236 patients (48.0%) who underwent revascularization. The mean age was 66 years, and 71% of patients
RESEARCH CORRESPONDENCE
were men. Just over one-half of the patients pre-
Clinical Outcomes of
FFRangio-Guided
Treatment for Coronary
Artery Disease
sented with acute coronary syndromes. The revascularization group was older, with a more accentuated
male predominance, and had a higher prevalence
of diabetes and multivessel disease. All other characteristics were similar between the 2 groups.
At 1 year, MACE occurred in 6 and 9 patients in the
deferral and revascularization groups (cumulative
incidence 2.5% and 4.1%), respectively. Incidence of
Several angiogram-based fractional flow
reserve
the secondary endpoints was 0.7% and 0.4% for car-
(abFFR) methods have shown good diagnostic per-
diovascular death, 0.9% and 1.4% for MI, and 2.1%
formance compared with wire-based FFR (wbFFR).1
and 3.8% for RR in the deferral and revascularization
However, unlike wbFFR, there is currently a paucity
groups, respectively (Figure 1).
of data on clinical outcomes of abFFR-guided
treatment for coronary artery disease (CAD).
The FFRangio system (CathWorks) (Figure 1) is an
abFFR
technology
that
has
shown
The main findings of our study are that in realworld patients, for 91.8% of cases, the treatment
strategy recommended by FFRangio was imple-
excellent
mented by the operators and that 1-year MACE for
diagnostic performance compared with wbFFR.2 We
FFRangio-guided treatment was low and consistent
examined the 1-year clinical outcomes of FFRangio-
with reported outcome data with wbFFR; Cerrato
guided treatment for CAD at 2 early-adopting centers
et al 3 reported data from 5 large international
of the FFRangio technology: Rabin Medical Centre
registries of all comers undergoing wbFFR-guided
(Petach Tikva, Israel) and Gifu Heart Centre (Gifu,
treatment (n ¼ 10,019), in 8,579 of whom (85.6%)
Japan). Both centers participated in studies that
the operators adhered to the wbFFR-recommended
examined the diagnostic performance of FFRangio
treatment. One-year rates of MACE (death, MI, or
compared with wbFFR and, following these studies,
RR) were 6.3% and 3.2% for the revascularization
started using FFRangio to guide treatment decisions
and deferral groups, respectively, compared with
in
4.1% and 2.5% in our cohort. For the individual
patients
undergoing
angiography,
without
the concomitant measurement of wbFFR.
components, the risk in the revascularization groups
Exclusion criteria were presentation of ST-segment
was 1.8% versus 1.4% for MI and 4.5% versus 3.8%
myocardial infarction (MI), left main disease, chronic
for RR in the cohort of Cerrato et al and our
total occlusion, and stent restenosis. In addition,
cohort, respectively. For the deferral group, the
patients were excluded if wbFFR was measured
corresponding risks were 0.6% versus 0.9% for MI
concomitantly with FFRangio or if intravascular im-
and 2.3% versus 2.1% for RR. Putting those figures
aging was used. When the treatment decision chosen
in clinical context, our results are very reassuring
by the operator was discordant with FFRangio (ie,
regarding
revascularization for lesions with FFRangio $ 0.8 or
FFRangio in real-world clinical practice.
the
safety
and
feasibility
of
using
deferral for lesions with FFRangio < 0.8), patients
Our study had several limitations. The sample size
were excluded as well. The primary endpoint was
was moderate, and follow-up was only 1 year, resulting
1-year major adverse cardiac events (MACE), defined
in few endpoint events; most important, we cannot
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 15, NO. 4, 2022
Letters
FEBRUARY 28, 2022:462–470
F I G U R E 1 Clinical Outcomes of FFRangio-Guided Treatment for Coronary Artery Disease
(Top) Schematic presentation of the study design. (Bottom) Baseline characteristics of the study cohort stratified according to treatment group (left) and Kaplan-Meier
curves for the primary outcome and breakdown of its components (right). ACS ¼ acute coronary syndrome; CABG ¼ coronary artery bypass grafting;
CV ¼ cardiovascular; CVA ¼ cerebrovascular accident; LAD ¼ left anterior descending coronary artery; LCx ¼ left circumflex coronary artery; MI ¼ myocardial infarction;
PCI ¼ percutaneous coronary intervention; RCA ¼ right coronary artery; RR ¼ repeat revascularization.
compare our results with a strategy of wbFFR-guided
treatment and therefore formally assess the equivalence or noninferiority of FFRangio-guided treatment
to those of wbFFR-guided treatment and examine
other possible benefits of using abFFR, such as time
savings,4 cost-effectiveness, and resources utilization.
In summary, our results suggest that at experienced centers, FFRangio-guided treatment for CAD
seems feasible and yields comparable 1-year clinical
outcomes as those described for wbFFR in large allcomers
cohorts.
A
randomized
comparison
of
Amos Levi, MD
Yeela Talmor-Barkan, MD, PhD
Aviad Rotholz, MD
Toru Tanigaki, MD
Masafumi Nakayama, MD, PhD
Hiroyuki Omori, MD, PhD
Ryosuke Itakura, MD, PhD
Yoshiaki Kawase, MD
Hitoshi Matsuo, MD, PhD
Ran Kornowski, MD
*Rabin Medical Center
abFFR- versus wbFFR-guided treatment is warranted
Department of Cardiology
to establish the role of abFFR in the treatment of
39 Jabotinsky Road
patients with CAD.
Petach Tikva 4941492, Israel
E-mail: vitberguy@gmail.com
https://doi.org/10.1016/j.jcin.2021.11.039
*Guy Witberg, MD
Tamir Bental, MD
Ó 2022 Published by Elsevier on behalf of the American College of Cardiology
Foundation
469
470
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 15, NO. 4, 2022
Letters
FEBRUARY 28, 2022:462–470
Dr Kornowski is cofounder of, owns intellectual property in, and is a shareholder of CathWorks. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and
animal welfare regulations of the authors’ institutions and Food and Drug
Administration guidelines, including patient consent where appropriate. For
more information, visit the Author Center.
2. Witberg G, De Bruyne B, Fearon WF, et al. Diagnostic performance
of angiogram-derived fractional flow reserve: a pooled analysis of 5
prospective cohort studies. J Am Coll Cardiol Intv. 2020;13(4):488–
497.
3. Cerrato E, Mejía-Rentería H, Dehbi HM, et al. Revascularization
deferral of nonculprit stenoses on the basis of fractional flow reserve:
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