Postprocedural Contrast Mediated FFR Plus Intracoronary Infusion of Nitroglycerin in Multivessel Patients (PROMETEUS TRIAL)

Official title

Postprocedural Contrast Mediated FFR Plus Intracoronary Infusion of Nitroglycerin in Multivessel Patients

Overview

the use of pressure wires is the standar of care to evaluate angiographically intermediate coronary lesions, however, limitations in the management of these type of lesions continue to be a challenge for the interventional cardiologist. The use of FFR has some limitations such as the use of adenosine due to its cost, adverse effects (e.g. transient atrioventricular block, angina, headache, etc.), time consuming and some relative contraindications for its use. In this sense, in recent years new rest indices (iFR, RFR, dPR) and hyperemic indices without adenosine (cFFR-NTG, Pd/Pa-NTG or cFFR) have been developed, demonstrating an improvement in terms of outcomes with its use, so they can also be used as a tool to guide us to plan our strategy. These new indices, particularly the cFFR-NTG, are simpler, at least as safe and have an excellent correlation with the FFR with adenosine in the assessment of intermediate coronary lesions. In recent years, functional assessment after intervention has also been increasingly implemented, which, like intracoronary imaging, can make us change our attitude and correlate with the prognosis. The lower implementation of this practice, especially in multivessel patients, may result from having to lose the position of the wire to check equalization, difficulty in crossing the wire, wear/breakage of the material after diagnosis (2-3 vessels), use more time and contrast, etc. These problems could be reduced, at least partially, with the use of the workhorse coronary guidewire pressure microcatheter to measure post-PCI functional assessment. Although the usefulness of post-PCI FFR has been demonstrated, there is no clearly established cut-off value (0.84-0.96) and it seems that in reality the values are a continuum of risk so that the higher the value, the better the prognosis . Furthermore, other simpler indices such as rest or hyperemic indices without adenosine have not been correlated with FFR in post-PCI. The purpose of this study is to evaluate the correlation between cFFR-NTG and other indices taking FFR as a reference in multivessel patients after undergoing intervention. Establish cut-off points and correlate it with adverse cardiovascular events (MACE) in a 1-year clinical follow-up.

Detailed description

Percutaneous coronary intervention (PCI) is a standard treatment strategy for coronary artery disease (CAD). With the presence of myocardial ischemia, PCI reduces the risks of death, myocardial infarction (MI), and revascularization compared to medical therapy. However, the risk of future clinical events remains high, and about 10% of patients experienced further cardiovascular events after PCI. Facing intermediate coronary lesions the use of pressure wires is the standar of care, however, limitations in the management of angiographically intermediate coronary lesions continue to be a challenge for the interventional cardiologist. The measurement of fractional flow reserve (FFR) to determine the hemodynamic relevance of coronary stenosis has been shown to be a technique that improves the prognosis and cost-efficiency of the procedures when compared to visual angiographic interpretation alone. Due to this evidence, the use of FFR to guide interventional procedures is a class I recommendation in current clinical practice guidelines.

Patients with multivessel coronary artery disease are another field in the use of pressure guiding. In these patients, the use of FFR has demonstrated the reclassification of the severity of coronary lesions in up to 40% of cases, modifying the number of functionally significant lesions and making it possible to reorient therapeutic decisions, avoiding interventional treatment of non-significant lesions and with a better prognosis.

However, the use of FFR has some limitations such as the use of adenosine due to its cost, adverse effects (e.g. transient atrioventricular block, angina, headache, etc.) and time consuming. In addition, the presence of atrioventricular block, asthma or severe chronic obstructive pulmonary disease are relative contraindications for its use. In this sense, in recent years new rest indices (iFR, RFR, dPR) and hyperemic indices without adenosine (cFFR-NTG, Pd/Pa-NTG or cFFR) have been developed , demonstrating an improvement in terms of outcomes with its use, so they can also be used as a tool to guide us to plan our strategy. These new indices, particularly the cFFR-NTG, are simpler, at least as safe and have an excellent correlation with the FFR with adenosine in the assessment of intermediate coronary lesions.

In recent years, functional assessment after intervention has also been increasingly implemented, which, like intracoronary imaging, can make us change our attitude and correlate with the prognosis. The lower implementation of this practice, especially in multivessel patients, may result from having to lose the position of the wire to check equalization, difficulty in crossing the wire, wear/breakage of the material after diagnosis (2-3 vessels), use more time and contrast, etc. These problems could be reduced, at least partially, with the use of the workhorse coronary guidewire pressure microcatheter to measure post-PCI functional assessment. Although the usefulness of post-PCI FFR has been demonstrated, there is no clearly established cut-off value (0.84-0.96) and it seems that in reality the values are a continuum of risk so that the higher the value, the better the prognosis . Furthermore, other simpler indices such as rest or hyperemic indices without adenosine have not been correlated with FFR in post-PCI.

The purpose of this study is to evaluate the correlation between cFFR-NTG and other indices taking FFR as a reference in multivessel patients after undergoing intervention. Establish cut-off points and correlate it with adverse cardiovascular events (MACE) in a 1-year clinical follow-up.

Interventions

• Diagnostic test Fractional Flow Reserve
  Agreement measurements between the different post-ICP functional values (cFFR+NTG and FFR) will be performed at the end of the intervention on the treated vessels. The study protocol consists of 4 sequential steps (separated by at least 30 sec): 1. Determination of FFR with contrast and NTG: cFFR +NTG will be calculated with the lowest ratio after the infusion of 0.2 mg bolus of intracoronary NTG and pushed with contrast. 2. Determination of distal pressure between basal aortic pressure: The Pd

Primary outcome measures

• Agreement between cFFR+NTG and FFR [Time frame: Index Procedure]
• SAFETY: MACE [Time frame: 12 months]

Secondary outcome measures (9)

• Agreement between Pd/Pa or dPR and FFR [Time frame: Index Procedure]
• Cut-off point for cFFR+NTG post-ICP [Time frame: Index Procedure]
• Evaluate the change in strategy that the measurement of FFR values ≤0.90 post-PCI [Time frame: Index Procedure]
• Cardiac death [Time frame: 12 months]
• Cardiovascular death [Time frame: 12 months]
• Acute myocardial infarction of the lesion treated/functionally evaluated [Time frame: 12 months]
• Acute myocardial infarction from any lesion [Time frame: 12 months]
• Need for revascularization of the lesion treated/functionally evaluated [Time frame: 12 months]
• Need for revascularization of any lesion [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Patients >18 years old and,
• Patients with multivessel coronary artery disease (multivessel coronary artery disease will be considered the presence of significant stenosis in 2 or more first or second order vessels greater than 1.5 mm in diameter with an angiographic reduction of their diameter ≥50% by visual estimation) subsidiary of percutaneous coronary revascularization in at least one of them and,
• Use of Navvus pressure microcatheter both for functional diagnosis and for post-PCI evaluation of the different vessels and,
• Patients who have signed the Informed Consent.

Exclusion criteria

• Patients with intolerance or contraindication to adenosine.
• Hemodynamically unstable patients, acute phase of a STEACS.
• Patient with significant comorbidity with limited life expectancy.
• Patients with the patient's express refusal to participate in the study.
• Pregnant or breastfeeding female patients.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Spain · 4 centers

• Hospital Universitario San Juan de Alicante — Alicante
• Hospital Universitario de Badajoz — Badajoz
• Hospital Universitario Juan Ramón Jiménez — Huelva
• Hospital Universitario Virgen del Rocío — Seville

Publications

• Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Juni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019 Jan 7;40(2):87-165. doi: 10.1093/eurhear PMID 30165437
• van Nunen LX, Zimmermann FM, Tonino PA, Barbato E, Baumbach A, Engstrom T, Klauss V, MacCarthy PA, Manoharan G, Oldroyd KG, Ver Lee PN, Van't Veer M, Fearon WF, De Bruyne B, Pijls NH; FAME Study Investigators. Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet. 2015 No PMID 26333474
• Gutierrez-Barrios A, Noval-Morillas I, Camacho-Freire S, Puche JE, Gheorghe L, Silva E, Alarcon-Lastra I, Canadas-Pruano D, Gomez-Menchero A, Calle-Perez G, Diaz-Fernandez JF, Vazquez-Garcia R. Contrast FFR plus intracoronary injection of nitro-glycerine accurately predicts FFR for coronary stenosis functional assessment. Minerva Cardiol Angiol. 2021 Aug;69(4):449-457. doi: 10.23736/S2724-5683.20. PMID 33258564
• Patel MR, Jeremias A, Maehara A, Matsumura M, Zhang Z, Schneider J, Tang K, Talwar S, Marques K, Shammas NW, Gruberg L, Seto A, Samady H, Sharp ASP, Ali ZA, Mintz G, Davies J, Stone GW. 1-Year Outcomes of Blinded Physiological Assessment of Residual Ischemia After Successful PCI: DEFINE PCI Trial. JACC Cardiovasc Interv. 2022 Jan 10;15(1):52-61. doi: 10.1016/j.jcin.2021.09.042. PMID 34991824
• Thakur U, Khav N, Comella A, Michail M, Ihdayhid AR, Poon E, Nicholls SJ, Ko B, Brown AJ. Fractional Flow Reserve following Percutaneous Coronary Intervention. J Interv Cardiol. 2020 Jun 5;2020:7467943. doi: 10.1155/2020/7467943. eCollection 2020. PMID 32565755

Identifiers

NCT: NCT06273293 · EPIC35-PROMETEUS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗