Clinical trial NCT01553513: PET/CT for the Quantification of Atherosclerotic Plaque Inflammation
Official title: PET/CT for the Quantification of Atherosclerotic Plaque Inflammation in Patients With Coronary Heart Disease: The QAEK Trial
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Artery Disease
Acute Coronary Syndrome
Keywords: PET
Coronary Artery Disease
Inflammation
Plaque
Atherosclerosis
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2012-03-14
Enrollment: 140
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with stable coronary artery disease or with acute coronary syndrome

Brief summary: This is a single-centre prospective trial with 140 patients employing \[18F\]-fluorodeoxyglucose positron emission computed tomography (FDG PET/CT) and advance motion correction and image fusion algorithms to create motion frozen displays and quantify FDG-uptake and thus inflammatory activity in atherosclerotic plaques in the coronary tree. Four groups of patients, two with stable coronary artery disease and two with acute coronary syndrome will be compared and the results of FDG PET/CT will be correlated to results of invasive coronary angiography, intravascular ultrasound / virtual histology, patient risk profile and serum markers of inflammation.

The investigators hypothesize that increased FDG accumulation in atherosclerotic plaques shows a positive correlation with inflammatory activity in coronary plaques and markers of plaque vulnerability as well as the risk profile of the patients and serum markers of inflammation. The investigators furthermore hypothesize that FDG PET/CT is able to detect high risk patients and provide an important means for risk stratification and optimization of patient management.

Detailed description: Currently there are only morphological reference standards to detect vulnerable coronary plaques. However, inflammatory activity and plaque composition predict future cardiovascular events. Thus the aims and objectives of the study are the following:

1. Inflammatory activity of the coronary arteries and the great peripheral arteries shall be detected and quantified by means of FDG PET/CT hybrid imaging.
2. We aim to develop "motion frozen displays" of the heart and coronary arteries by means of ECG- and respiratory triggering of myocardial motion to reduce motion artifacts.
3. We aim to compare the coronary FDG uptake of patients with known stable CAD to the coronary FDG uptake of patients with acute coronary syndrome.
4. We aim to correlate coronary PET/CT with intravascular ultrasound (IVUS) / virtual histology (VH), which will be carried out during coronary angiography and provides the gold standard to characterize plaque composition.
5. Correlation of the inflammatory activity as measured by PET with the risk profile of the patients, blood coagulability and inflammatory and plaque-associated serum markers to establish a valid risk stratification.
6. Follow-up of the patients over at least one year to detect cardiovascular events.

Study Design

This is a prospective single-center study to evaluate coronary FDG PET/CT under controlled and standardized conditions. The study was approved by the local ethical committee as well as the German Federal Authority for Radiation Protection (Bundesamt für Strahlenschutz). All examinations will be performed at the University Hospital of the LMU in Munich. The study is in accordance with the Declaration of Helsinki, all patients provide informed written consent.

We plan to image four study populations with a high risk for inflammatory atherosclerosis or plaque rupture: two groups consist of patients with stable coronary disease and two groups consist of patients with acute coronary syndrome (Figure 1).

In the following, these groups will be described in more detail.

Patients with acute coronary syndrome Group 1: Patients with acute cardiovascular event and typical aberrations in the ECG (STEMI) and positive serum markers need to be stabilized immediately, thus they are not eligible for IVUS. However, by means of ICA the "culprit lesion" can be identified. 48 to 72 hours after the event the stable patients will receive FDG PET/CT to detect morphology and inflammation of the culprit lesion as well as further vulnerable plaques that might need intervention. PET/CT results will be correlated with results of ICA.

Group 2: Patients with acute coronary syndrome without typical aberrations in the ECG (NSTEMI) or without positive serum markers need to be stabilized immediately. In a second step ICA and IVUS / VH will be performed. 48 to 72 hours after the event the stable patients will receive FDG PET/CT to detect morphology and inflammation of the culprit lesion as well as further vulnerable plaques that might need intervention. PET/CT results will be correlated with results of ICA and IVUS / VH.

Patients with stable CAD Group 3: Symptomatic patients with stable CAD, who are eligible for ICA will receive and additional FDG PET/CT scan as well as IVUS / VH. Results will be correlated.

Group 4: Patients eligible for ICA 6 months after STEMI and revascularization will receive IVUS / VH and FDG PET/CT. Results will be correlated with regard to the former culprit lesion as well as further coronary lesions that might be present.

Summary of working hypotheses

Hypothesis 1 (technique) By means of FDG PET/CT the radiotracer uptake in the coronary arteries can be allocated to specific lesions and quantified with the aid of appropriate techniques for motion correction and three-dimensional image fusion.

Hypothesis 2 (association of FDG-uptake and extent of the disease) The coronary FDG-uptake of patients with stable CAD is significantly lower than the coronary FDG-uptake of patients with acute coronary syndrome.

Hypothesis 3 (correlation between IVUS/VH and FDG-uptake) Plaques with typical signs of vulnerability in IVUS/VH show a significantly increased FDG-uptake as a surrogate marker of inflammatory activity.

Hypothesis 4 (association of FDG-uptake and risk profile / serum markers) Coronary FDG-uptake shows a positive correlation with increasing risk profile (Framingham Score) and serum markers for plaque vulnerability and inflammatory reactions.

Hypothesis 5 (association of FDG-uptake and cardiovascular events) Increased coronary FDG-uptake and increased uptake in the peripheral vessels are associated with cardiovascular and cerebrovascular events over the course of one year.

Eligibility criteria: Inclusion Criteria:

* symptomatic patients with known STEMI or NSTEMI and/or known CAD (see patient groups above)
* written informed consent for blood samples, ICA, IVUS/VH and FDG PET/CT

Exclusion Criteria:

* less than 50 years of age
* reason for symptoms other than coronary stenoses / occlusion
* known contraindication for the above listed examinations (like iodine allergy, intolerance of contrast media, claustrophobia)
* patients, who are not able to lie still without changing position over a minimum of 45 minutes
* pregnancy, breast feeding
* restricted renal function (creatinine \> 1,5 mg% in women, \> 2mg% in men)
* surgery within prior 24 hours

Primary outcomes:
measure: Association of FDG uptake and coronary plaque vulnerability
timeFrame: within 72 hours after enrollment
Secondary outcomes:
measure: Association of FDG-uptake and extent of the disease
timeFrame: within 72 hours after enrollment
measure: Association of FDG-uptake and risk profile / serum markers
timeFrame: within 72 hours after enrollment
measure: Association of FDG-uptake and cardiovascular events
timeFrame: within 1 year of follow-up
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Department of Nuclear Medicine, Departmen of Cardiology, University of Munich
state: Bavaria
Study officials:
affiliation: LMU Munich
name: Marcus Hacker, MD
role: PRINCIPAL_INVESTIGATOR
References: