INOCA-NA a Local Prospective Registry (INOCA-NA)

Ischemia in Patients with Non- Obstructive Disease (INOCA) - a Local Prospective Registry (INOCA-Naples)

The present study has the following objectives:

1. To investigate the prevalence of INOCA in patients referring for a clinically indicated coronary angiography (CA) c/o Division of Cardiology - Federico II University Hospital;
2. To stratify in INOCA endotypes patients according to the presence or absence of alternative (i.e. non obstructive CAD) causes of myocardial ischemia detected during CA clinically indicated through physiology tests;
3. to implement a stratified therapy in these patients considering the different INOCA endotypes and evaluate the impact on angina class and quality of life as well as cardiac hospitalization and coronary revascularization during 5 year follow up

Study Overview

• Status: Recruiting
• Conditions: Non-Obstructive Coronary Atherosclerosis; Ischemia, Myocardial; Coronary Microvascular Dysfunction (CMD); Microcirculatory Status

Detailed Description

Eligible patients with angina and/or positive stress test undergoing clinical indicated CA detecting non-obstructive CAD will be studied as follows:

• Functional evaluation by fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), Resting Full-Cycle Ratio (RFR) of any stenosis that is angio- graphically considered > 50%;

• In case of stenosis <50% or >50% but with negative functional evaluation (FFR >0.80 and iFR/RFR

  >0.90), coronary flow reserve (CFR) and index of microvascular resistance (IMR) will be performed. IMR and CFR will be evaluated, using an intracoro- nary wire;

• In case of CFR>2.0 and IMR<25, acetylcholine test will be performed. Intracoronary acetylcholine (ACh) will be administrated to detect epicardial (fo- cal or diffuse) or microvascular spasm.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Luigi Di Serafino, MD, PhD; Phone Number: 0039 347917374; Email: luigi.diserafino@unina.it

Study Locations

• Italy
  • Naples, Italy, 80131
    • Recruiting
    • DPT of Advanced Biomedical Sciences
    • Contact: Stefano Cristiano; Phone Number: +300817463075; Email: stefano.cristiano@unina.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients presenting with signs or symptoms potentially related to myocardial ischemia and requiring a functional coronary angiography for specific diagnosis will be enrolled.

Description

Inclusion Criteria:

• Clinical presentation of chronic ischemic heart dis- ease (IHD), requiring coronary angiography for the diagnosis;
• Absence of obstructive coronary artery disease (CAD) at coronary angiography;
• Age > 18 years.
• Ability to provide a valid informed consent to the study procedure at the time of baseline evaluation;

Exclusion Criteria:

Clinical presentation of acute coronary syndrome (ACS) or cardiogenic shock;

• Presence of obstructive CAD with at least 1 significant coronary artery stenosis, defined as diameterstenosis >50% and FFR ≤0.80 (or iFR/RFR ≤0.89);
• Previous coronary artery bypass grafting (CABG);
• Left ventricular systolic dysfunction, defined as ejection fraction (EF) <40%;
• Severe valvular heart disease;
• Pregnant or breastfeeding women
• Known hypersensitivity or contraindication to any of the drugs used for coronary physiology testing (adenosine, nitrates, acetylcholine)
• Inability or unwillingness to provide a valid in- formed consent to the study procedure at the time of baseline evaluation.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
INOCA; Patients presenting with symptoms or signs of myocardial ischemia with non-obstructing coronary artery disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACE	Occurrence of Cardiovascular death, Myocardial infarction, Coronary revascularization	12 and 60 months
Degree of Angina	The degree of angina will be assessed using The Seattle Angina Questionnaire - 7 (SAQ-7) contains 7 questions used to measure health status in patients with coronary artery disease (CAD). The score is generated for each domain and it is scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status.	12 and 60 months
QoL	Quality of life will be assessed using the 5-level EuroQoL 5-dimensions Questionnaire (EQ-5D-5L). The EQ-5D-5L descriptive system comprises the same five dimensions as the EQ-5D-3L (MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN/DISCOMFORT and ANXIETY / DEPRESSION), but each dimension has five response levels: no problems, slight problems, moderate problems, severe problems, unable to/extreme problems. The respondent is asked to indicate his/her health state by checking the box next to the most appropriate response level for each of the five dimensions. Responses are coded as single-digit numbers expressing the severity level selected in each dimension. An EQ-5D health state is deemed to be 'better' than another if it is better on at least one dimension and is no worse in any other dimension. An EQ-5D health state is deemed to be 'worse' than another if it is worse in at least one dimension and is no better in any other dimension.	12 and 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
TIMI Frame Count	To evaluate the accuracy of TIMI Frame Count (TFC) to identify specific INOCA endotypes. TFC will be evaluated dunring invasive assessement before and after administration of nitrates. Patients with different INOCA endotypes will be compared in terms of TFC.	up to 24 hours
EndoPAT_Endoscore	To evaluate whether the assessment of peripheral microcirculation, as assessed with EndoPAT test might be useful to identify specific INOCA endotypes. The EndoPAT detects plethysmographic pressure changes in the finger tips caused by the arterial pulse and translates this to a peripheral arterial tone (PAT). We will evaluate the Endoscore which has been previosly reported to be significantly decreased in patients with coronary artery disease, thereby the lower the endoscore the higher the risk of endothelial dysfunction.	1 day and 12 months
EndoPAT_RH	To evaluate whether the assessment of peripheral microcirculation, as assessed with EndoPAT test might be useful to identify specific INOCA endotypes. The EndoPAT detects plethysmographic pressure changes in the finger tips caused by the arterial pulse and translates this to a peripheral arterial tone (PAT). We will evaluate the Reactive Hyperemic Index (RHI) which has been found to be significantly decreased in patients with coronary artery disease, thereby the lower the RHI values the higher the risk of endothelial dysfunction.	1 day and 12 months
Nitrates effects on CFR	To evaluate any changes in terms of hemodynamic parameters after i.c. administration of nitrates, which is normally administered during the invasive functional coronary angiography. In particular, we will evaluate the Coronary Flow Reserve (CFR), measured as the ratio between the mean transit time at rest and the mean transit time during maximal hyperemia.	up to 5 minutes
Nitrates effects on MMR	To evaluate any changes in terms of hemodynamic parameters after i.c. administration of nitrates, which is normally administered during the invasive functional coronary angiography. In particular, we will evaluate the Microvascular resistance reserve (MRR), measured as the ratio between the CFR and the fractional flow reserve (FFR) corrected for driving pressure.	up to 5 minutes

Collaborators and Investigators

• Sponsor: Federico II University

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: August 29, 2024
• First Submitted That Met QC Criteria: September 4, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: INOCA; CMD; VSA
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Ischemia; Coronary Artery Disease; Myocardial Ischemia; Atherosclerosis
• Other Study ID Numbers: 160/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Privacy concerns

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No