Clinical trial NCT04531007: Imaging and Physiology for Intermediate Left Main Stem Stenosis
Official title: Validation of Intravascular Imaging and Physiology for Intermediate Left Main Stem Stenosis With Downstream Coronary Lesions
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Coronary Artery Disease Left Main
Keywords: Left Main Coronary Artery (LMCA)
FFR
iFR
OCT
IVUS
intracoronary imaging
Lead sponsor: Instituto Dante Pazzanese de Cardiologia
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2020-08-28
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The present research aims to determine the impact of stenoses in downstream vessels on the FFR and iFR measurements of left main coronary artery (LMCA) stenoses of intermediate severity as determined by coronary angiography. Anatomic metrics derived from intravascular imaging modalities of IVUS and optical coherence tomography (OCT) will also be validated using as the comparator the FFRtrue and iFRtrue measurements pf LMCA lesions.

Detailed description: Accurate characterization of the functional significance of intermediate stenoses located in the left main coronary artery (LMCA) is of central relevance for decisions about the need of myocardial revascularization. However, the physiological assessment of such lesions by means of fractional flow reserve (FFR) measurements are affected by stenoses in the downstream vessels (left anterior descending artery and/or left circumflex artery), which frequently coexist in series with LMCA lesions. More recently introduced, the instantaneous wave-free ratio (iFR) is a resting index that is less influenced by crosstalk between serial lesions and, in theory, could be more accurate for assessment of LMCA stenoses in the presence of downstream disease. Nonetheless, iFR has not been validated for assessment of LMCA lesions. Due to the difficulty in interpreting FFR results, the possibility of characterizing the atheroma type, precisely estimate lesion severity and disease extension and distribution, intravascular imaging \[especially intravascular ultrasound (IVUS)\] became an attractive alternative to assess LMCA lesions and guide the percutaneous treatment, whenever this strategy is selected. However, most IVUS validations for LMCA stenosis assessment used FFR as the standard comparator, which by itself has limited diagnostic ability in this anatomic scenario.

Thus, the main objective of the current research project is to determine the impact of stenoses in downstream vessels on FFR and iFR measurements of LMCA stenoses of intermediate severity as determined by coronary angiography. The primary endpoint is the change (delta) in FFR and iFR values prior and after percutaneous treatment of downstream stenoses. Assuming a change of 0.04 mmHg between the FFRpredicted and FFRtrue with a standard deviation of 0.04 mmHg, and a change of 0.01 mmHg between iFRpredicted and iFRtrue with a standard deviation of 0.03 mmHg, a total of 53 patients are needed to confirm the mean difference of 0.03 mmHg between iFR and FFR changes before and after treatment of downstream stenoses. Anatomic metrics derived from intravascular imaging modalities of IVUS and optical coherence tomography (OCT) will also be validated using as the comparator the FFRtrue and iFRtrue measurements.

Eligibility criteria: Inclusion Criteria:

- age \>/= 18 years;

* patients who have an intermediate (40-70% diameter stenosis) lesion located in the LMS and a concomitant significant (\>/=70% diameter stenosis) in one of the two major downstream vessels (the LAD or the LCx). The severity of LMS and downstream lesions will be assessed by visual estimation of the coronary angiography;
* need of complementary diagnostic work up to ascertain the functional/physiological significance of the LMS lesion, that is not possible from the analysis of angiographic images only:

  * Intermediate severity of LMS lesion, or angiographic ambiguity;
  * Impossibility to conclusively associate the LMS lesion with the patient's symptoms/clinical presentation due to confounders introduced by the significant downstream lesion;
  * Impossibility to conclusively determine the severity and functional/physiological significance of the LMS lesion solely by the visual analysis of the coronary angiography;
  * Impossibility to conclusively determine the relative contribution of the LMS lesion to the ischemic burden determined by non-invasive functional tests due to the presence of a significant downstream lesion;
* Clinical indication for PCI of the downstream lesion located in the LAD or LCx:

  * stable angina unresponsive to optimized medical treatment;
  * important ischemic burden (\> 10% of myocardial mass in territories supplied by the diseased vessels);
  * Reduced FFR/iFR values indicative of myocardial ischemia with significant pressure gradient across the downstream lesion;
  * Acute coronary syndrome without ST elevation or stabilized (\>7 days) acute myocardial infarction;
* Downstream lesion anatomically suited for PCI;
* LMS anatomy suited for PCI, with a low or intermediate SYNTAX score (\< 32);
* Lack of contra-indications for second-generation drug-eluting stents and/or use of dual antiplatelet therapy for at least 6 months.

Exclusion Criteria:

Left ventricular ejection fraction £ 40%;

* Renal dysfunction with a glomerular filtration rate £ 45 mL/min;
* Concomitance of right coronary artery occlusion supplied by collateral circulation from the left coronary;
* Prior coronary artery bypass graft with at least on patent graft to any vessel of the left coronary;
* Concomitant significant valvular heart disease;
* The first 7 days of an acute myocardial infarction;
* Downstream lesion located only in branches from the major downstream vessels (e.g. diagonal branches of LAD or obtuse marginal branches of the LCx);
* Downstream lesions located in the distal segments of LAD or LCx;
* Significant tortuosity of the downstream vessels in which difficulty to navigate with the physiology wire and/or intravascular imaging catheter is anticipated

Primary outcomes:
measure: Change of iFR and FFR values of the LMS stenosis before and after PCI of the significant downstream stenosis
timeFrame: diagnostic procedure
measure: Accuracy of intravascular imaging in predicting functionally signifcant LMS stenosis
timeFrame: diagnostic procedure
Secondary outcomes:
measure: Accuracy of pressure changes in the iFR and FFR pullback curves before PCI of the downstream lesion in predicting the functional significance of LMS stenosis
timeFrame: diagnostic procedure
measure: Accuracy of iFRpred-contra and FFRpred-contra before PCI of the downstream lesion in predicting the functional significance of LMS stenosis
timeFrame: diagnostic procedure
measure: Agreement of the iFRcontra and FFRcontra after PCI of the downstream stenosis with the iFRtrue and FFRtrue.
timeFrame: diagnostic procedure
measure: Accuracy of minimum lumen area determined by IVUS and OCT in the LMS to predict the functional significance of LMS stenosis
timeFrame: diagnostic procedure
measure: Accuracy of minimum lumen diameter determined by IVUS and OCT in the LMS to predict the functional significance of LMS stenosis
timeFrame: diagnostic procedure
measure: Accuracy of percent diameter stenosis determined by IVUS and OCT in the LMS to predict the functional significance of LMS stenosis
timeFrame: diagnostic procedure
measure: Accuracy of percent area stenosis determined by IVUS and OCT in the LMS to predict the functional significance of LMS stenosis
timeFrame: diagnostic procedure
measure: Accuracy of lesion length determined by IVUS and OCT in the LMS to predict the functional significance of LMS stenosis
timeFrame: diagnostic procedure
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
Study officials:
affiliation: Instituto Dante Pazzanese de Cardiologia
name: Daniel Chamie, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Dante Pazzanese de Cardiologia
name: Fausto Feres, MD, PhD
role: STUDY_CHAIR
References: