Clinical trial NCT03205514: Multimodality Investigation of Intermediate Culprit Lesion With Negative FFR in NSTE-ACS
Official title: Multimodality Investigation of Intermediate Culprit Lesion With Negative Fractional Flow Reserve in Patients With no ST-segment Elevation Acute Coronary Syndrome.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myocardial Ischemia
Lead sponsor: University Hospital of Ferrara
Sponsor class: OTHER
First posted: 2017-07-02
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: NSTE-ACS patients with intermediate culprit lesion (40-70%) and negative FFR (\>0.80).

Brief 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Plaque erosion incidence
timeFrame: intra-procedure
Secondary outcomes:
measure: Incidence of intermediate lesions with negative FFR in NSTE-ACS
timeFrame: intra-procedure
measure: Vessel Lipid burden
timeFrame: intra-procedure
measure: Plaque Lipid burden
timeFrame: intra-procedure
measure: Apoptosis rate in HUVEC
timeFrame: intra-procedure
measure: NO intracellular levels
timeFrame: intra-procedure
measure: ROS production
timeFrame: intra-procedure
measure: Inflammation markers levels
timeFrame: intra-procedure
measure: Ischemic adverse events
timeFrame: 1 year
Other outcomes:
Locations:
city: Cona
country: Italy
facility: University Hospital of Ferrara
state: Ferrara
Study officials:
affiliation: Ferrara University Hospital
name: Simone Biscaglia, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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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.
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