Multimodality Investigation of Intermediate Culprit Lesion With Negative FFR in NSTE-ACS

Myocardial Ischemia Clinical Trial

— SHERLOCK  

Official title:

Multimodality Investigation of Intermediate Culprit Lesion With Negative Fractional Flow Reserve in Patients With no ST-segment Elevation Acute Coronary Syndrome.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03205514
• Other study ID #: 160487
• Status: Completed
• Start date: June 28, 2017
• Est. completion date: April 28, 2021

Study information

• Verified date: April 2021
• Source: University Hospital of Ferrara
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Ten-fifteen percent of acute coronary syndromes without ST-segment elevation (NSTE-ACS) are caused by intermediate lesions without signs of unstable plaque. In this subset of patients, fractional flow reserve (FFR) has some drawbacks and may not be always able to predict outcome, especially when negative (above 0.80). In this particular nique of patients, advanced imaging techniques are suggested by International guidelines. However, it is actually unknown how these techniques may impact treatment strategies. With the present study, the investigators want to characterize the mechanism of disease in this particular subset of patients through multimodality imaging (intravascular ultrasound-near infrared spectroscopy (IVUS-NIRS), optical coherence tomography (OCT)) in order to understand the proper treatment.

Description:

Acute coronary syndrome without ST-segment elevation (NSTE-ACS) is by far the most frequent acute coronary syndrome (ACS) in the western world. In most of the cases, it is caused by a clearly identifiable culprit lesion, configuring a significant angiographic stenosis (>70%), with flux limitation and typical aspects of unstable plaque (thrombosis). In these cases, the one and only treatment is stent implantation. In a small percentage of patients (10-15%), NSTE-ACS is caused by an angiographically intermediate lesion (40-70%). This lesion is identifiable as culprit, but without the typical signs of unstable plaque.

In patients with stable coronary artery disease (SCAD) presenting with this type of lesion, fractional flow reserve (FFR) is the actual gold-standard for ischemic burden evaluation. Several studies showed that if FFR value is ≤0.80, the treatment with percutaneous coronary intervention (PCI) is associated with a significant reduction of hard cardiovascular events. When FFR is negative (>0.80), optical medical therapy showed a better outcome when compared to percutaneous intervention. In NSTE-ACS, FFR evaluation of intermediate lesions is still mandatory, as a recent study showed a better outcome in patient with positive fractional flow reserve treated invasively with stenting compared to patients treated solely based on angiography (1). When FFR is negative, several authors and studies suggest that further imaging techniques are needed. In this subgroup of patients with intermediate stenosis without angiographic evidence of plaque rupture, European Guidelines (2) suggest utilization of intravascular ultrasound-near infrared spectroscopy (IVUS-NIRS) or optical coherence tomography (OCT) in order to better characterize the culprit plaque. At the same time, the therapeutic strategy is left to the operator's discretion: some implant a stent in order to reduce occurrence of future events, while some others leave the patient in optical medical therapy without stent implantation. Moreover, in these patients, it is still unclear the pathophysiology of the disease leading to ACS. In the last years, researchers focused their attention on plaque erosion, deemed to be responsible for most of these NSTE-ACS (3). An imaging study evaluated the incidence of plaque erosion in patients with ACS (4). This study enrolled an heterogeneous group of patients, evaluated with a single imaging technique (OCT).

Based on these background, the investigators hypothesized to perform a prospective single-center data registry on this highly selected subgroup of patients: NSTE-ACS with culprit intermediate lesion with negative FFR evaluation.

Investigators will enroll consecutive patients with NSTE-ACS with a culprit intermediate stenosis between 40 and 70% and in whom FFR evaluation will result negative (>0.80). In these patients, the operator will perform IVUS-NIRS and OCT and a blood sample to evaluate endothelial function as per our previous experience (5). The study has no control group. Endothelial function and inflammatory state will be evaluated in all patients and will be compared to those obtained by patients enrolled in the NATHAN NEVER study (NCT02519608, Study ID: 150497)(5).

Aim of the present study is to understand whether in this group of patient endothelial function is impaired and which information is given by intracoronary imaging (presence of plaque erosion). The present study is a prospective data collection. Thus, a formal sample size calculation is not applicable. Contemporaneously, for pilot studies, at least 30 patients are recommended (6).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: April 28, 2021
• Est. primary completion date: June 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• diagnosis of no-ST elevation-acute coronary syndrome

• clinical indication to coronary artery angiography

• angiographic documentation of intermediate lesion (40%-70%) with anterograde TIMI 3 flow eligible for FFR evaluation

• negative FFR evaluation (>0.80)

Exclusion Criteria:

• cardiogenic shock

• any indication to stent treatment for lesion

• previous stent implantation on the target vessel

• left main disease

• massive thrombus presence in the culprit vessel

• life expectancy less than 12 months

Related Conditions & MeSH terms

• Ischemia
• Myocardial Ischemia

Intervention

Diagnostic Test:
• NSTE-ACS with intermediate stenosis and negative FFR
Patients will undergo intracoronary imaging evaluation with IVUS-NIRS and OCT, endothelial function and inflammatory state evaluation.

Locations

Country	Name	City	State
Italy	University Hospital of Ferrara	Cona	Ferrara

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital of Ferrara

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Campo G, Vieceli Dalla Sega F, Pavasini R, Aquila G, Gallo F, Fortini F, Tonet E, Cimaglia P, Del Franco A, Pestelli G, Pecoraro A, Contoli M, Balla C, Biscaglia S, Rizzo P, Ferrari R. Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease. Thromb Haemost. 2017 Mar 23;117(6):1208-1216. doi: 10.1160/TH16-12-0973. Epub 2017 Mar 23. — View Citation

Jia H, Abtahian F, Aguirre AD, Lee S, Chia S, Lowe H, Kato K, Yonetsu T, Vergallo R, Hu S, Tian J, Lee H, Park SJ, Jang YS, Raffel OC, Mizuno K, Uemura S, Itoh T, Kakuta T, Choi SY, Dauerman HL, Prasad A, Toma C, McNulty I, Zhang S, Yu B, Fuster V, Narula J, Virmani R, Jang IK. In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography. J Am Coll Cardiol. 2013 Nov 5;62(19):1748-58. doi: 10.1016/j.jacc.2013.05.071. Epub 2013 Jun 27. — View Citation

Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract. 2004 May;10(2):307-12. — View Citation

Layland J, Oldroyd KG, Curzen N, Sood A, Balachandran K, Das R, Junejo S, Ahmed N, Lee MM, Shaukat A, O'Donnell A, Nam J, Briggs A, Henderson R, McConnachie A, Berry C; FAMOUS-NSTEMI investigators. Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS-NSTEMI randomized trial. Eur Heart J. 2015 Jan 7;36(2):100-11. doi: 10.1093/eurheartj/ehu338. Epub 2014 Sep 1. — View Citation

Libby P, Pasterkamp G. Requiem for the 'vulnerable plaque'. Eur Heart J. 2015 Nov 14;36(43):2984-7. doi: 10.1093/eurheartj/ehv349. Epub 2015 Jul 22. Review. — View Citation

Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S; ESC Scientific Document Group . 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016 Jan 14;37(3):267-315. doi: 10.1093/eurheartj/ehv320. Epub 2015 Aug 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plaque erosion incidence	OCT-erosion: evidence of thrombotic material, irregular luminal surface without evidence of plaque fissure in multiple adjacent frames.; IVUS/NIRS erosion: evidence of thrombotic material, irregular luminal surface without evidence of plaque fissure in multiple adjacent frames with lipid core burden index lower than the validated cutoff for unstable plaque (LCBI 4mm<400).	intra-procedure
Secondary	Incidence of intermediate lesions with negative FFR in NSTE-ACS	Incidence of intermediate lesions with negative FFR in the whole population of NSTE-ACS	intra-procedure
Secondary	Vessel Lipid burden	Vessel Lipid burden at IVUS-NIRS evaluation (total LCBI) in patients with intermediate plaque and negative FFR	intra-procedure
Secondary	Plaque Lipid burden	Plaque Lipid burden at IVUS-NIRS evaluation (max LCBI 4 mm) in patients with intermediate plaque and negative FFR	intra-procedure
Secondary	Apoptosis rate in HUVEC	Rate of apoptosis in human umbilical vein endothelial cells (HUVEC) incubated with serum from patients enrolled in the study.	intra-procedure
Secondary	NO intracellular levels	Modulation of intracellular levels of nitric oxid (NO) in HUVECs treated with serum from patients enrolled in the study	intra-procedure
Secondary	ROS production	Intracellular levels of reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) isolated from patients enrolled in the study	intra-procedure
Secondary	Inflammation markers levels	Values of the most important inflammation cytokines (hs-PCR, fibrinogen, IL-6, IL-1Ra, TNF-alpha)	intra-procedure
Secondary	Ischemic adverse events	Cumulative incidence of ischemic adverse events (death, myocardial infarction, stent thrombosis).	1 year