Observational Study

. 2024 Aug 20;150(8):586-597.

doi: 10.1161/CIRCULATIONAHA.124.069450. Epub 2024 May 14.

Influence of Pathophysiologic Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes

Carlos Collet¹, Daniel Munhoz^{1

2}, Takuya Mizukami^{1

3}, Jeroen Sonck¹, Hitoshi Matsuo⁴, Toshiro Shinke⁵, Hirohiko Ando⁶, Brian Ko⁷, Simone Biscaglia⁸, Fernando Rivero⁹, Thomas Engstrøm¹⁰, Ketina Arslani¹⁰, Antonio Maria Leone^{11

12

13}, Lokien X van Nunen¹⁴, William F Fearon¹⁵, Evald Høj Christiansen¹⁶, Stephane Fournier¹⁷, Liyew Desta¹⁸, Andy Yong¹⁹, Julien Adjedj²⁰, Javier Escaned²¹, Masafumi Nakayama²², Ashkan Eftekhari²³, Frederik M Zimmermann²⁴, Koshiro Sakai^{1

5}, Tatyana Storozhenko^{1

25}, Bruno R da Costa^{26

27}, Gianluca Campo⁸, Nick E J West²⁸, Tom De Potter¹, Ward Heggermont¹, Dimitri Buytaert¹, Jozef Bartunek¹, Colin Berry^{29

30}, Damien Collison^{29

30}, Thomas Johnson³¹, Tetsuya Amano⁶, Divaka Perera³², Allen Jeremias³³, Ziad Ali³³, Nico H J Pijls²⁴, Bernard De Bruyne^{1

17}, Nils P Johnson³⁴

Affiliations

¹ Cardiovascular Center Aalst, OLV Clinic, Aalst, Belgium (C.C., D.M., T.M., J.S., K.S., T. Storozhenko, T.D.P., W.H., D.B., J.B., B.D.B.).
² Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy (D.M.).
³ Division of Clinical Pharmacology, Department of Pharmacology, Showa University, Tokyo, Japan (T.M.).
⁴ Department of Cardiovascular Medicine, Gifu Heart Center, Japan (H.M.).
⁵ Department of Medicine, Division of Cardiology, Showa University School of Medicine, Tokyo, Japan (T. Shinke, K.S.).
⁶ Department of Cardiology, Aichi Medical University, Japan (H.A., T.A.).
⁷ Monash Cardiovascular Research Centre, Monash University and Monash Heart, Monash Health, Clayton, Victoria, Australia (B.K.).
⁸ Cardiology Unit, Azienda Ospedaliera Universitaria di Ferrara, Italy (S.B., G.C.).
⁹ Cardiac Department, Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain (F.R.).
¹⁰ Rigshospitalet, University of Copenhagen, Denmark (T.E., K.A.).
¹¹ Department of Cardiovascular Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy (A.M.L.).
¹² IRCCS, Catholic University School of Medicine, Largo A. Gemelli, Rome, Italy (A.M.L.).
¹³ Center of Excellence in Cardiovascular Diagnostics and Therapeutic, Ospedale Fabenefratelli Isola Tiberina Gemelli Isola, Rome, Italy (A.M.L.).
¹⁴ Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (L.X.v.N.).
¹⁵ Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University School of Medicine and VA Palo Alto Health Care System, Palo Alto, CA (W.F.F.).
¹⁶ Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark (E.H.C.).
¹⁷ Department of Cardiology, University Hospital of Lausanne, Switzerland (S.F., B.D.B.).
¹⁸ Department of Cardiology, Karolinska University Hospital, Solna, Stockholm, Sweden (L.D.).
¹⁹ Concord Repatriation General Hospital, University of Sydney, New South Wales, Australia (A.Y.).
²⁰ Department of Cardiology, Arnault Tzanck Institute Saint Laurent du Var, France (J.A.).
²¹ Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos and Complutense University, Madrid, Spain (J.E.).
²² Department of Cardiology, Tokyo D Tower Hospital, Japan (M.N.).
²³ Department of Cardiology, Aalborg University Hospital, Denmark (A.E.).
²⁴ Department of Cardiology, Catharina Hospital Eindhoven, the Netherlands (F.M.Z., N.H.J.P.).
²⁵ Department of Prevention and Treatment of Emergency Conditions, L.T. Malaya Therapy National Institute NAMSU, Kharkiv, Ukraine (T. Storozhenko).
²⁶ Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (B.R.d.C.).
²⁷ Clinical Epidemiology & Health Care Research, Institute of Health Policy and Management Evaluation, University of Toronto, Canada (B.R.d.C.).
²⁸ Abbott Vascular, Santa Clara, CA (N.E.J.W.).
²⁹ School of Cardiovascular and Metabolic Health, University of Glasgow, UK (C.B., D.C.).
³⁰ NHS Golden Jubilee Hospital, Clydebank, UK (C.B., D.C.).
³¹ University Hospitals Bristol & Weston NHS Foundation Trust, Bristol, UK (T.J.).
³² School of Cardiovascular Medicine and Sciences, St Thomas' Hospital Campus, King's College London, UK (D.P.).
³³ St Francis Hospital and Heart Center, Roslyn, NY (A.J., Z.A.).
³⁴ Weatherhead PET Center, Division of Cardiology, Department of Medicine, McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, TX (N.P.J.).

PMID: 38742491
PMCID: PMC11335079
DOI: 10.1161/CIRCULATIONAHA.124.069450

Observational Study

Influence of Pathophysiologic Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes

Carlos Collet et al. Circulation. 2024.

. 2024 Aug 20;150(8):586-597.

doi: 10.1161/CIRCULATIONAHA.124.069450. Epub 2024 May 14.

Authors

Affiliations

¹ Cardiovascular Center Aalst, OLV Clinic, Aalst, Belgium (C.C., D.M., T.M., J.S., K.S., T. Storozhenko, T.D.P., W.H., D.B., J.B., B.D.B.).
² Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy (D.M.).
³ Division of Clinical Pharmacology, Department of Pharmacology, Showa University, Tokyo, Japan (T.M.).
⁴ Department of Cardiovascular Medicine, Gifu Heart Center, Japan (H.M.).
⁵ Department of Medicine, Division of Cardiology, Showa University School of Medicine, Tokyo, Japan (T. Shinke, K.S.).
⁶ Department of Cardiology, Aichi Medical University, Japan (H.A., T.A.).
⁷ Monash Cardiovascular Research Centre, Monash University and Monash Heart, Monash Health, Clayton, Victoria, Australia (B.K.).
⁸ Cardiology Unit, Azienda Ospedaliera Universitaria di Ferrara, Italy (S.B., G.C.).
⁹ Cardiac Department, Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain (F.R.).
¹⁰ Rigshospitalet, University of Copenhagen, Denmark (T.E., K.A.).
¹¹ Department of Cardiovascular Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy (A.M.L.).
¹² IRCCS, Catholic University School of Medicine, Largo A. Gemelli, Rome, Italy (A.M.L.).
¹³ Center of Excellence in Cardiovascular Diagnostics and Therapeutic, Ospedale Fabenefratelli Isola Tiberina Gemelli Isola, Rome, Italy (A.M.L.).
¹⁴ Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (L.X.v.N.).
¹⁵ Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Stanford University School of Medicine and VA Palo Alto Health Care System, Palo Alto, CA (W.F.F.).
¹⁶ Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark (E.H.C.).
¹⁷ Department of Cardiology, University Hospital of Lausanne, Switzerland (S.F., B.D.B.).
¹⁸ Department of Cardiology, Karolinska University Hospital, Solna, Stockholm, Sweden (L.D.).
¹⁹ Concord Repatriation General Hospital, University of Sydney, New South Wales, Australia (A.Y.).
²⁰ Department of Cardiology, Arnault Tzanck Institute Saint Laurent du Var, France (J.A.).
²¹ Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos and Complutense University, Madrid, Spain (J.E.).
²² Department of Cardiology, Tokyo D Tower Hospital, Japan (M.N.).
²³ Department of Cardiology, Aalborg University Hospital, Denmark (A.E.).
²⁴ Department of Cardiology, Catharina Hospital Eindhoven, the Netherlands (F.M.Z., N.H.J.P.).
²⁵ Department of Prevention and Treatment of Emergency Conditions, L.T. Malaya Therapy National Institute NAMSU, Kharkiv, Ukraine (T. Storozhenko).
²⁶ Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (B.R.d.C.).
²⁷ Clinical Epidemiology & Health Care Research, Institute of Health Policy and Management Evaluation, University of Toronto, Canada (B.R.d.C.).
²⁸ Abbott Vascular, Santa Clara, CA (N.E.J.W.).
²⁹ School of Cardiovascular and Metabolic Health, University of Glasgow, UK (C.B., D.C.).
³⁰ NHS Golden Jubilee Hospital, Clydebank, UK (C.B., D.C.).
³¹ University Hospitals Bristol & Weston NHS Foundation Trust, Bristol, UK (T.J.).
³² School of Cardiovascular Medicine and Sciences, St Thomas' Hospital Campus, King's College London, UK (D.P.).
³³ St Francis Hospital and Heart Center, Roslyn, NY (A.J., Z.A.).
³⁴ Weatherhead PET Center, Division of Cardiology, Department of Medicine, McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, TX (N.P.J.).

PMID: 38742491
PMCID: PMC11335079
DOI: 10.1161/CIRCULATIONAHA.124.069450

Abstract

Background: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes.

Methods: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI.

Results: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61-0.69]; P<0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P<0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50-0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97]).

Conclusions: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317.

Keywords: coronary artery disease; hemodynamics; percutaneous coronary intervention.

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Conflict of interest statement

Dr Collet reports receiving research grants from Biosensors, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; consultancy fees from HeartFlow, OpSens Medical, Abbott Vascular, and Philips Volcano; and has patents pending on diagnostic methods for coronary artery disease. Dr Munhoz reports a research grant provided by the CardioPath PhD programme and speaker fees from Abbott Vascular. Dr Mizukami reports receiving research grants from Boston Scientific and speaker fees from Abbott Vascular, CathWorks, and Boston Scientific. Dr Matsuo has received consulting fees from Kaneka and Zeon and speaker’s fees from Abbott Medical Japan, Boston Scientific, Philips, and Amgen. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Biscaglia received research grants provided by Sahajanand Medical Technologies, Medis Medical Imaging, Eukon Srl, Siemens Healthineers, General Electric Healthcare, and Insight Lifetech. Dr Engstrøm reports speaker and advisory board fees from Abbott, Boston Scientific, and Novo Nordisk. Dr Leone reports receiving consultancy fees from Abbott and honoraria for sponsored symposia from Abbott, Medtronic, and Abiomed. Dr Fearon receives institutional research support from Abbott, Boston Scientific, and Medtronic and has consulting relationships with CathWorks and Siemens and stock options from HeartFlow. Dr Christiansen has received consulting fees from Abbott Medical Denmark A/S. Dr Yong has received minor honoraria from Abbott Vascular and research grants from Abbott Vascular and Philips. Dr Escaned is supported by the Intensification of Research Activity project INT22/00088 from the Spanish Instituto de Salud Carlos III and received speaker and advisory board member fees from Abbott and Philips. Dr Storozhenko reports a grant provided by the EAPCI Fellowship Programme. Dr West is an employee of Abbott Vascular. Dr De Potter is a paid consultant for Biosense Webster and receives grant support (institutional) and consultancy fees (institutional) from Abbott. Dr Berry receives research funding from the British Heart Foundation (grants RE/18/6134217, BHF/FS/17/26/32744, and PG/19/28/34310) and is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis Research, GlaxoSmithKline, HeartFlow, Menarini, Novartis, Servier, Siemens Healthcare, and Valo Health. Dr Collison has received consulting fees from Abbott. Dr Johnson has received consultancy or speaker fees from Abbott Vascular, Boston Scientific, Medtronic, Shockwave, and Terumo, and research grants from Abbott Vascular. Dr Amano reports receiving lecture fees from Astellas Pharma, Astra Zeneca, Bayer, Daiichi Sankyo, and Bristol Myers Squibb. Dr Perera has received research grant support from Abbott Vascular, HeartFlow, and Philips. Dr Jeremias has received consulting fees from Canon Medical, Artrya Medical, and Boston Scientific. Dr Ali reports institutional grant support from Abbott, Abiomed, Acist, Amgen, Boston Scientific, CathWorks, Canon Medical, Conavi, HeartFlow, Inari, Medtronic, the US National Institutes of Health, Nipro, OpSens Medical, Medis, Philips, Shockwave, Siemens, SpectraWAVE, and Teleflex; consulting fees from Abiomed, Astra Zeneca, Boston Scientific, CathWorks, OpSens Medical, Philips, and Shockwave; and equity in Elucid, Lifelink, SpectraWAVE, Shockwave, and VitalConnect. Dr Pijls has received research grants from Abbott and Hexacath; consultancy fees from Abbott, GE, Philips, and HeartFlow; and has equity in General Electric, Philips, and HeartFlow. Dr De Bruyne reports receiving consultancy fees from Boston Scientific and Abbott and research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular. Dr Johnson received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St Jude Medical (CONTRAST [Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02184117]) and Philips Volcano (DEFINE-FLOW [Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02328820]) for other studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm (now commercialized under 510[k] K191008); and has patents pending on diagnostic methods for quantifying aortic stenosis and TAVI physiology and on methods to correct pressure tracings from fluid-filled catheters.

Figures

**Figure 1.**
**Study flow chart**. CABG indicates coronary artery bypass graft; eGFR, estimated glomerular filtration rate; FFR, fractional flow reserve; OMT, optimal medical therapy; PCI, percutaneous coronary intervention; and PPG, pullback pressure gradient.

**Figure 2.**
**Correlation between pullback pressure gradient and fractional flow reserve before and after percutaneous coronary intervention. A**, Relationship between pullback pressure gradient (PPG) and fractional flow reserve (FFR) after percutaneous coronary intervention (PCI). B, Relationship between PPG and delta FFR (%): ([post-PCI FFR – pre-PCI FFR]/[1 – pre-PCI FFR]). C, Relationship between PPG and change in FFR after PCI; the triangles indicate the FFR at baseline, and the circles the post-PCI FFR. The length of the lines displays the change in FFR. The blue lines indicate PCI, where FFR after PCI was ≥0.88, and the red lines where post-PCI FFR was <0.88. P values were derived from Pearson correlation.

**Figure 3.**
**Predictive capacity of pullback pressure gradient for fractional flow reserve after percutaneous coronary intervention. Left**, The predictive capacity of pullback pressure gradient for predicting a fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) ≥0.88. **Right**, the mean difference between the prediction of FFR in the validation cohort derived from the pullback pressure gradient regression analysis and measured post-PCI FFR. AUC indicates area under the receiver operating characteristic curve.

**Figure 4.**
**Case examples of focal and diffuse coronary artery disease. A**, Angiogram of a left anterior descending artery with a lesion in the mid segment. B, Fractional flow reserve (FFR) with a pullback before percutaneous coronary intervention (PCI). This case had an FFR of 0.77 with a pullback pressure gradient of 0.81. C, Angiogram after PCI. D, Post-PCI FFR of 0.90. E, Angiogram of a left anterior descending artery with a lesion in the mid segment. F, FFR of 0.55 with a pullback pressure gradient of 0.42, pointing at diffuse coronary artery disease. G, Post-PCI angiogram. H, Post-PCI FFR of 0.66.

**Figure 5.**
**In-hospital clinical outcomes after percutaneous coronary intervention in patients with predominantly focal or diffuse disease on the basis of pullback pressure gradient.** Patients were stratified on the basis of the median pullback pressure gradient value of 0.62 into predominantly focal or diffuse disease. A, Incidence of target vessel failure (TVF) and its components. B, Rate of target vessel myocardial infarction (MI) stratified by periprocedural or spontaneous MI. The incidence of periprocedural MI was significantly higher in patients with diffuse disease. P value was calculated using the Fisher exact test. ID-TVR indicates ischemia-driven target vessel revascularization.

See this image and copyright information in PMC

Comment in

Does PPG, the Other Dimension to FFR, Better Predict Post-PCI Results?
Kern MJ, Seto AH. Kern MJ, et al. Circulation. 2024 Aug 20;150(8):598-599. doi: 10.1161/CIRCULATIONAHA.124.070439. Epub 2024 Aug 19. Circulation. 2024. PMID: 39159226 No abstract available.

References

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1. Collet C, Sonck J, Vandeloo B, Mizukami T, Roosens B, Lochy S, Argacha J-F, Schoors D, Colaiori I, Di Gioia G, et al. . Measurement of hyperemic pullback pressure gradients to characterize patterns of coronary atherosclerosis. J Am Coll Cardiol. 2019;74:1772–1784. doi: 10.1016/j.jacc.2019.07.072 - PubMed
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1. Collet C, Collison D, Mizukami T, McCartney P, Sonck J, Ford T, Munhoz D, Berry C, De Bruyne B, Oldroyd K. Differential improvement in angina and health-related quality of life after PCI in focal and diffuse coronary artery disease. JACC Cardiovasc Interv. 2022;15:2506–2518. doi: 10.1016/j.jcin.2022.09.048 - PubMed

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Influence of Pathophysiologic Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes

Affiliations

Influence of Pathophysiologic Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes

Authors

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Conflict of interest statement

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