. 2020 Jul 8;9(7):2147.

doi: 10.3390/jcm9072147.

Sequential Strategy Including FFR_CT Plus Stress-CTP Impacts on Management of Patients with Stable Chest Pain: The Stress-CTP RIPCORD Study

Andrea Baggiano¹, Laura Fusini¹, Alberico Del Torto^{1

2}, Patrizia Vivona^{1

2}, Marco Guglielmo¹, Giuseppe Muscogiuri¹, Margherita Soldi¹, Chiara Martini³, Enrico Fraschini¹, Mark G Rabbat^{4

5}, Francesca Baessato⁶, Gloria Cicala⁷, Maria L Danza⁸, Annachiara Cavaliere⁹, Antonella Loffreno¹⁰, Vitanio Palmisano¹¹, Francesca Ricci¹², Giulia Rizzon⁹, Elisabetta Tonet¹³, Giacomo M Viani^{1

2}, Saima Mushtaq¹, Edoardo Conte¹, Andrea D Annoni¹, Alberto Formenti¹, Maria E Mancini¹, Franco Fabbiocchi¹, Piero Montorsi^{1

2}, Daniela Trabattoni¹, Alexia Rossi^{14

15}, Fabio Fazzari¹⁵, Nicola Gaibazzi¹⁶, Daniele Andreini^{1

2}, Emilio M Assanelli¹, Antonio L Bartorelli^{1

17}, Mauro Pepi¹, Andrea I Guaricci¹⁸, Gianluca Pontone¹

Affiliations

¹ Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy.
² Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, 20122 Milan, Italy.
³ Department of Radiology, Azienda Ospedaliero-Universitaria, 43126 Parma, Italy.
⁴ Loyola University Medical Center, Center for Heart & Vascular Medicine, Maywood, IL 60153, USA.
⁵ Edward Hines Jr. VA Hospital, Hines, IL 60141, USA.
⁶ Divisione di Cardiologia, Dipartimento di Medicina, Università degli Studi, 37134 Verona, Italy.
⁷ Dipartimento di Medicina e Chirurgia, Azienda Ospedaliero-Universitaria di Parma, Università degli Studi, 43126 Parma, Italy.
⁸ Division of Cardiology, University of Rome Tor Vergata, 00133 Rome, Italy.
⁹ Dipartimento di Medicina, Istituto di Radiologia, Università degli Studi, 35128 Padova, Italy.
¹⁰ U.O.C. Cardiologia 1, Ospedale di Circolo e Fondazione Macchi, Università degli Studi, 21100 Varese, Italy.
¹¹ Diagnostica per Immagini, Università degli Studi di Cagliari, Monserrato, 09042 Cagliari, Italy.
¹² Department of Biomedicine and Prevention Division of Diagnostic Imaging University of Rome Tor Vergata, 00133 Rome, Italy.
¹³ Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona, 44124 Ferrara, Italy.
¹⁴ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy.
¹⁵ Department of Diagnostic Imaging, Humanitas Research Hospital, Rozzano, 20089 Milan, Italy.
¹⁶ Unità Operativa di Cardiologia, Azienda Ospedaliero-Universitaria di Parma, Università degli Studi, 43126 Parma, Italy.
¹⁷ Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, 20157 Milan, Italy.
¹⁸ Institute of Cardiovascular Disease, Department of Emergency and Organ Transplantation, University Hospital Policlinico of Bari, 70124 Bari, Italy.

PMID: 32650379
PMCID: PMC7408909
DOI: 10.3390/jcm9072147

Sequential Strategy Including FFR_CT Plus Stress-CTP Impacts on Management of Patients with Stable Chest Pain: The Stress-CTP RIPCORD Study

Andrea Baggiano et al. J Clin Med. 2020.

. 2020 Jul 8;9(7):2147.

doi: 10.3390/jcm9072147.

Authors

Affiliations

¹ Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy.
² Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, 20122 Milan, Italy.
³ Department of Radiology, Azienda Ospedaliero-Universitaria, 43126 Parma, Italy.
⁴ Loyola University Medical Center, Center for Heart & Vascular Medicine, Maywood, IL 60153, USA.
⁵ Edward Hines Jr. VA Hospital, Hines, IL 60141, USA.
⁶ Divisione di Cardiologia, Dipartimento di Medicina, Università degli Studi, 37134 Verona, Italy.
⁷ Dipartimento di Medicina e Chirurgia, Azienda Ospedaliero-Universitaria di Parma, Università degli Studi, 43126 Parma, Italy.
⁸ Division of Cardiology, University of Rome Tor Vergata, 00133 Rome, Italy.
⁹ Dipartimento di Medicina, Istituto di Radiologia, Università degli Studi, 35128 Padova, Italy.
¹⁰ U.O.C. Cardiologia 1, Ospedale di Circolo e Fondazione Macchi, Università degli Studi, 21100 Varese, Italy.
¹¹ Diagnostica per Immagini, Università degli Studi di Cagliari, Monserrato, 09042 Cagliari, Italy.
¹² Department of Biomedicine and Prevention Division of Diagnostic Imaging University of Rome Tor Vergata, 00133 Rome, Italy.
¹³ Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona, 44124 Ferrara, Italy.
¹⁴ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy.
¹⁵ Department of Diagnostic Imaging, Humanitas Research Hospital, Rozzano, 20089 Milan, Italy.
¹⁶ Unità Operativa di Cardiologia, Azienda Ospedaliero-Universitaria di Parma, Università degli Studi, 43126 Parma, Italy.
¹⁷ Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, 20157 Milan, Italy.
¹⁸ Institute of Cardiovascular Disease, Department of Emergency and Organ Transplantation, University Hospital Policlinico of Bari, 70124 Bari, Italy.

PMID: 32650379
PMCID: PMC7408909
DOI: 10.3390/jcm9072147

Abstract

Stress computed tomography perfusion (Stress-CTP) and computed tomography-derived fractional flow reserve (FFR_CT) are functional techniques that can be added to coronary computed tomography angiography (cCTA) to improve the management of patients with suspected coronary artery disease (CAD). This retrospective analysis from the PERFECTION study aims to assess the impact of their availability on the management of patients with suspected CAD scheduled for invasive coronary angiography (ICA) and invasive FFR. The management plan was defined as optimal medical therapy (OMT) or revascularization and was recorded for the following strategies: cCTA alone, cCTA+FFR_CT, cCTA+Stress-CTP and cCTA+FFR_CT+Stress-CTP. In 291 prospectively enrolled patients, cCTA+FFR_CT, cCTA+Stress-CTP and cCTA+FFR_CT+Stress-CTP showed a similar rate of reclassification of cCTA findings when FFR_CT and Stress-CTP were added to cCTA. cCTA, cCTA+FFR_CT, cCTA+Stress-CTP and cCTA+FFR_CT+Stress-CTP showed a rate of agreement versus the final therapeutic decision of 63%, 71%, 89%, 84% (cCTA+Stress-CTP and cCTA+FFR_CT+Stress-CTP vs cCTA and cCTA+FFR_CT: p < 0.01), respectively, and a rate of agreement in terms of the vessels to be revascularized of 57%, 64%, 74%, 71% (cCTA+Stress-CTP and cCTA+FFR_CT+Stress-CTP vs cCTA and cCTA+FFR_CT: p < 0.01), respectively, with an effective radiation dose (ED) of 2.9 ± 1.3 mSv, 2.9 ± 1.3 mSv, 5.9 ± 2.7 mSv, and 3.1 ± 2.1 mSv. The addition of FFR_CT and Stress-CTP improved therapeutic decision-making compared to cCTA alone, and a sequential strategy with cCTA+FFR_CT+Stress-CTP represents the best compromise in terms of clinical impact and radiation exposure.

Keywords: clinical management; computed tomography; coronary artery disease; fractional flow reserve; myocardial perfusion.

PubMed Disclaimer

Conflict of interest statement

Pontone G. declares an institutional research grant and/or honorarium as speaker from General Electric, Bracco, Medtronic, Bayer, Heartflow. Andreini D. declares an institutional research grant and/or honorarium as speaker from General Electric, Bracco, Heartflow. Other authors have no conflict of interest to disclose.

Figures

**Figure A1**
Study flow diagram. Consecutive symptomatic patients referred for suspected CAD and scheduled for clinically indicated ICA were screened. After the application of inclusion and exclusion criteria, 291 patients were enrolled, 147 in the first arm, in which Static Stress-CTP was performed, and 144 in the second arm, in which Dynamic Stress-CTP was performed. CAD: coronary artery disease; ICA: invasive coronary angiography; Stress-CTP: stress computed tomography perfusion.

**Figure A2**
Study protocol. Patients were asked to refrain from smoking and caffeine for 24 h and to maintain fasting for 6 h before the scan. All patients were treated with sublingual nitrates to ensure vasodilatation. In patients with a resting HR > 65 beats/min, metoprolol was intravenously administered, with a titration dose up to 15 mg to achieve a target HR ≤ 65 beats/min. However, all patients were studied even if the target HR was not reached. cCTA and FFR_CT were evaluated with the acquisition of the first dataset; then, after a period of fifteen minutes, perfusion evaluation was performed during adenosine administration with the acquisition of the second dataset (Static or Dynamic protocols were used according to the specific arm of the study). HR: heart rate; cCTA: coronary computed tomography angiography; FFR_CT: computed tomography-derived fractional flow reserve.

**Figure 1**
Clinical management algorithm. The clinical management algorithms to OMT, revascularization, or further information for cCTA alone (A), for the combined approach of cCTA+FFR_CT (B), for the combined approach of cCTA+Stress-CTP (C) and for the sequential approach of cCTA+FFR_CT+Stress-CTP (D) are illustrated. OMT: optimal medical treatment; cCTA: coronary computed tomography angiography; OMT: optimal medical treatment; ICA: invasive coronary angiography; FFR_CT: computed tomography-derived fractional flow reserve; Stress-CTP: stress computed tomography perfusion.

**Figure 2**
Management according to cCTA alone. Nearly one third of the population needed further assessment to be allocated to OMT or revascularization. cCTA: coronary computed tomography angiography; OMT: optimal medical treatment; ICA: invasive coronary angiography; iFFR: invasive fractional flow reserve.

**Figure 3**
Management according to the addition of FFR_CT to cCTA. If FFR_CT is added to cCTA, there is a substantial equal redistribution of patients previously without a clear management indication to OMT or to revascularization. cCTA: coronary computed tomography angiography; OMT: optimal medical treatment; ICA: invasive coronary angiography; FFR_CT: computed tomography-derived fractional flow reserve; iFFR: invasive fractional flow reserve.

**Figure 4**
Management according to the addition of Stress-CTP to cCTA. If Stress-CTP is added to cCTA, more than two-thirds of patients who were previously without a clear management indication were allocated to OMT. cCTA: coronary computed tomography angiography; OMT: optimal medical treatment; ICA: invasive coronary angiography; Stress-CTP: stress computed tomography perfusion; iFFR: invasive fractional flow reserve.

**Figure 5**
Management according to the sequential addition of FFR_CT and Stress-CTP to cCTA. If a sequential approach is used, patients without a clear management indication after FFR_CT analysis can be allocated to OMT or revascularization after Stress-CTP assessment. cCTA: coronary computed tomography angiography; OMT: optimal medical treatment; ICA: invasive coronary angiography; FFR_CT: computed tomography-derived fractional flow reserve; Stress-CTP: stress computed tomography perfusion; iFFR: invasive fractional flow reserve.

**Figure 6**
Primary endpoint of the study between different diagnostic strategies. Both the cCTA+Stress-CTP and cCTA+FFR_CT+Stress-CTP strategies showed a higher rate of agreement with the final decision as compared to cCTA alone and the cCTA+FFR_CT strategy. cCTA: coronary computed tomography angiography; Stress-CTP: stress computed tomography perfusion; FFR_CT: computed tomography-derived fractional flow reserve.

**Figure 7**
Secondary endpoints of the study between different diagnostic strategies. No differences were found in terms of evaluability between the different strategies. Both the cCTA+Stress-CTP and cCTA+FFR_CT+Stress-CTP strategies showed a higher rate of patient reclassification and rate of agreement for the target vessel to be revascularized as compared to cCTA alone and the cCTA+FFR_CT strategy. cCTA: coronary computed tomography angiography; Stress-CTP: stress computed tomography perfusion; FFR_CT: computed tomography-derived fractional flow reserve.

**Figure 8**
Radiation exposure. In terms of radiation exposure, the cCTA+Stress-CTP strategy was associated with the highest ED with a progressive reduction in the ED for cCTA+FFR_CT+Stress-CTP and cCTA+FFR_CT. cCTA: coronary computed tomography angiography; Stress-CTP: stress computed tomography perfusion, ED: effective dose; FFR_CT: computed tomography-derived fractional flow reserve.

**Figure 9**
Clinical Case. A 54 y/o male with hypertension, dyslipidaemia and recent onset of atypical chest pain. Panels (A–C): cCTA showing significant stenosis in the proximal LAD (A), moderate stenosis in the proximal LCx (B), and moderate stenosis in the mid RCA (C). Panels (D,E): FFR_CT showing grey-zone values in the apical LAD, negative values in the RCA and LCx. Panels (F–H): Static Stress-CTP with short axis views (F,G) and 2-chamber long axis view (H) showing absence of perfusion defects. Panels (I–K): ICA showing moderate stenoses in the proximal LAD (I) and LCx (J), and mild stenosis in the mid RCA (K), all with negative FFR values. cCTA: coronary computed tomography angiography; LAD: left anterior descending; LCx: left circumflex; RCA: right coronary artery; FFR_CT: computed tomography-derived fractional flow reserve; Stress-CTP: stress computed tomography perfusion; ICA: invasive coronary angiography; FFR: fractional flow reserve.

See this image and copyright information in PMC

References

1. Pontone G., Andreini D., Quaglia C., Ballerini G., Nobili E., Pepi M. Accuracy of multidetector spiral computed tomography in detecting significant coronary stenosis in patient populations with differing pre-test probabilities of disease. Clin. Radiol. 2007;62:978–985. doi: 10.1016/j.crad.2007.02.022. - DOI - PubMed
1. Min J.K., Dunning A., Lin F.Y., Achenbach S., Al-Mallah M., Budoff M.J., Cademartiri F., Callister T.Q., Chang H.J., Cheng V., et al. Age- and sex-related differences in all-cause mortality risk based on coronary computed tomography angiography findings results from the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) of 23,854 patients without known coronary artery disease. J. Am. Coll. Cardiol. 2011;58:849–860. doi: 10.1016/j.jacc.2011.02.074. - DOI - PubMed
1. Pontone G., Andreini D., Bartorelli A.L., Bertella E., Cortinovis S., Mushtaq S., Foti C., Annoni A., Formenti A., Baggiano A., et al. A long-term prognostic value of CT angiography and exercise ECG in patients with suspected CAD. JACC Cardiovasc. Imaging. 2013;6:641–650. doi: 10.1016/j.jcmg.2013.01.015. - DOI - PubMed
1. Investigators S.-H., Newby D.E., Adamson P.D., Berry C., Boon N.A., Dweck M.R., Flather M., Forbes J., Hunter A., Lewis S., et al. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction. N. Engl. J. Med. 2018;379:924–933. doi: 10.1056/NEJMoa1805971. - DOI - PubMed
1. Pontone G., Bertella E., Mushtaq S., Loguercio M., Cortinovis S., Baggiano A., Conte E., Annoni A., Formenti A., Beltrama V., et al. Coronary artery disease: Diagnostic accuracy of CT coronary angiography--a comparison of high and standard spatial resolution scanning. Radiology. 2014;271:688–694. doi: 10.1148/radiol.13130909. - DOI - PubMed

Grants and funding

R250/15-CCM 262/GE Healthcare, Milwaukee, WI, USA

LinkOut - more resources

Full Text Sources
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Sequential Strategy Including FFR_CT Plus Stress-CTP Impacts on Management of Patients with Stable Chest Pain: The Stress-CTP RIPCORD Study

Affiliations

Sequential Strategy Including FFR_CT Plus Stress-CTP Impacts on Management of Patients with Stable Chest Pain: The Stress-CTP RIPCORD Study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous