Presentation on theme: "Ron Waksman, MD on Behalf of the F1RST Investigators Fractional Flow Reserve and Intravascular Ultrasound RelationShip THE F1RST TRIAL."— Presentation transcript:
Ron Waksman, MD on Behalf of the F1RST Investigators Fractional Flow Reserve and Intravascular Ultrasound RelationShip THE F1RST TRIAL
Disclosure Statement of Financial Interest Grant/Research Support Consulting Fees/Honoraria Volcano Medtronic Vascular Abbott Vascular Boston Scientific Biotronik Medtronic Abbott Vascular Boston Scientific Lilly Daiichi Astra Zeneca Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial RelationshipCompany
Background I An intermediate coronary stenosis, defined as a luminal narrowing with a diameter stenosis between 40-70% on angiography, is a source of controversy with regard to the appropriate criteria for undertaking revascularization. It has been previously reported that postponing revascularization of intermediate severity lesions on angiography with FFR>0.80 is safe and results in an excellent clinical outcome.
Background II The PROSPECT trial followed 700 patients with acute coronary syndrome for 3 years, reported that the MACE was low with one of the correlated of non-culprit lesion related events was an MLA <4 mm 2 by IVUS To date, few data are available regarding the relationship between the anatomical and morphological IVUS parameters and the functional FFR results.
Purpose and Aims To evaluate the relationship between IVUS VH ® anatomical parameters and FFR value in patients with intermediate coronary stenoses. To determine the IVUS VH ® anatomical criteria and cutoff value associated with significantly functional criteria of FFR< 0.8.
Endpoints Primary Correlation between MLA and FFR and to identity a cut-off value for MLA corresponding to and FFR of 0.8 Secondary Correlation between FFR and plaque burden and to identify a cut-off value for plaque burden corresponding to and FFR of 0.8 Assess the relationship between FFR (<0.80) and determined cut-off values of MLA with Presence of: Thin cup fibroatheroma (TCFA) defined as Necrotic Core (NC) >10%, confluent over 3 consecutive frames with a plaque burden of > 40% and NC against the lumen surface > 30 degrees Plaque burden ≥ 70%
Hypothesis We hypothesize that IVUS VH morphological criteria, such as minimal lumen area, plaque burden and plaque type by VH, can predict can predict physiological ischemia by FFR.
Study participating Sites Site NameCity, State Country Principal Investigators # Enrolled Washington Hospital CenterWashington, DC USARon Waksman, MD 91 University Hospital KrakowKrakow, PolandJacek Legutko, MD 59 Barnes Jewish HospitalSt. Louis, MO USAJasvindar Singh, MD 49 Hamot Medical CenterErie, PA USAQuentin Orlando, MD 33 St. Luke’s Health CenterKansas City, MO USASteven Marso, MD 27 Patients FirstWashington, MO USATimothy Schloss, MD 26 Ohio Heart ResearchColumbus, OH USAJohn Tugaoen, MD 7 Dartmouth Medical CenterLebanon, NH USAJames DeVries, MD 6 Liverpool Heart and ChestLiverpool, United KingdomNicholas Palmer, MD 5 Städtische Kliniken NeussNeuss, GermanyMichael Haude, MD 1
Study Management Key Members SponsorVolcano Corp Study Principal InvestigatorRon Waksman, MD Data AnalysisCardiovascular Research Institute Rebecca Torguson Stacy Swymelar Zhenyi Xue QCA Core LaboratoryCardiovascular Research Institute Cathy Gurgol David Hellinga Rebecca Torguson IVUS Core LaboratoryKrakow Cardio-Vascular Research Institute Clinical MonitoringIMARC Research Inc & Krakow Cardio-Vascular Research Institute
Inclusion/Exclusion Criteria Inclusions Clinical indication for coronary angiography for stable or unstable angina Intermediate coronary lesion with stenosis 40-80% in one or more native, major epicardial coronary artery Lesions suitable for FFR and IVUS/VH Exclusions STEMI within the past 24 hours Decompensated HF or hypotension requiring intubation, inotropes, intravenous diuretics or IABP Left ventricular hypertrophy >1.5 cm by echo History of bronchospasm or asthma ECG evidence of conduction defect (2º or 3º AVB) Unprotected left main or ostial lesions Severe calcification or tortuosity of the target vessel Lesions in arterial or saphenous vein grafts Thrombus Lesion in a vessel with <2.5 mm reference diameter More than one lesion in an epicardial vessel
Methods We have enrolled 304 patients and 320 lesions at 10 sites in the United States and Europe, who were undergoing a clinically indicated coronary angiogram and who have intermediate coronary lesions. Where, clinical indication for coronary angiography was stable or unstable angina. Patients required to have an intermediate coronary lesion (stenosis 40-80% by visual estimate) in one or more native, major epicardial coronary artery (defined as LAD and subsequent branches, LCX and subsequent branches, and RCA and subsequent branches) with reference diameter ≥2.5mm (visual estimate) IVUS VH and FFR were performed to explore the relationship between those different imaging modalities. Data lock for this presentation was made on 24/OCT/2011 Clinical Trial.gov ID NCT
Intermediate lesion was identified by the operatorIntermediate lesion was identified by the operator FFR measured by pressure wire using either the RADI TM or the Volcano Wires hyperemia induced by i.v. adenosine 140 µg/kg/min in periheral veinFFR measured by pressure wire using either the RADI TM or the Volcano Wires hyperemia induced by i.v. adenosine 140 µg/kg/min in periheral vein IVUS VH was performed in the target vessel to assess lesion severityIVUS VH was performed in the target vessel to assess lesion severity The operator was free to decide whether to intervene or deferThe operator was free to decide whether to intervene or defer Independent IVUS and QCA core labs assessed blindly the Angio and the IVUS studies respectivelyIndependent IVUS and QCA core labs assessed blindly the Angio and the IVUS studies respectively Methods
Results Baseline DemographicsF1RST population (N=304) Age (years) 61.5 ± 9.9 Male 223 (73.4%) Hypertension 261 (86.1%) Hyperlipidemia 265 (88.0%) Current Smoker 58 (27.5%) History of Pulmonary Disease 21 (6.9%) History of CAD 22 (7.3%) Family history of CAD 134 (47.9%) Diabetes 92 (30.3%) IDDM 40 (13.1%) Renal Dysfunction 19 (6.3%) Prior PCI 144 (47.4%) Prior CABG 6 (2.0%) Prior myocardial infarction 94 (31.8%) Ejection fraction (%) 55.2 ± 10.7
IVUS MLA cut-off for ischemic FFR Cut off for FFR = mm 2 Sensitivity 73.8% Specificity 54.8% C= 0.64 Cut off for FFR = mm 2 Sensitivity 65.3% Specificity 65.6% C= 0.66
WHC IVUS FFR CUTOFF BY VESSEL SIZE (200 LESIONS)
Correlations r = P < FFR to MLA FFR to MLD r = P <
Correlations r = p = FFR to % Plaque Burden VH FFR to % Diameter Stenosis QCA r = p =
Correlations of FFR to MLA by RVD r = p = RVD < 3.0 mm r = p = RVD 3.0 to 3.5 mm r = p = RVD > 3.5 mm
r = p < Lesions without CaTCFA or TCFA Lesions with CaTCFA or TCFA r = p = Correlations of FFR to MLA by TCFA
FFR Correlation with VH VH Variable Mean ± SD r valuep value Plaque Burden, % 68.7 ± Plaque Area, mm 8.5 ± Necrotic Core Tissue, % 22.0 ± Necrotic Core Tissue, mm ± Fibrofatty Tissue, % 12.4 ± Fibrofatty Tissue, mm ± Fibrous Tissue, % 52.6 ± Fibrous Tissue, mm ± Dense Calcium, % 11.1 ± Dense Calcium, mm ± With FFR < 0.75n (%)kappap value Plaque Burden % < 70% 30 (9.4%) TCFA 1 (0.5%)
VH Findings by FFR VH VariableFFR < 0.8FFR ≥ 0.8P value Plaque Burden, % 72.1 ± ± Plaque Area, mm 8.7 ± ± Necrotic Core Tissue, % 21.8 ± ± Necrotic Core Tissue, mm ± Fibrofatty Tissue, % 13.7 ± ± Fibrofatty Tissue, mm ± ± Fibrous Tissue, % 54.5 ± ± Fibrous Tissue, mm ± ± Dense Calcium, % 10.0 ± ± Dense Calcium, mm ± ±
Conclusions The FIRST Study demonstrates modest correlation of IVUS anatomical to FFR physiological measurements in intermediate lesions The new IVUS cutoff for FFR of 0.80 is 2.99 mm 2 The new IVUS cutoff for FFR of 0.75 is 3.16 mm 2 Lesions without CaTCFA or TCFA had better correlation to FFR when compared to lesions with CaTCFA or TCFA FFR was correlated with plaque burden but was not correlated with plaque morphology The utility of IVUS as a tool to determine whether to intervene on borderline should be studied in a prospective study
Limitations This trial does not assess long term outcome with respect to the IVUS/FFR findings. Once this IVUS/FFR correlation has been established it would require to conduct an IVUS guided lesion assessment study to determine the need for intervention and the impact of this strategy on long term clinical outcome.