PET CT in Suspected CIED Infection, a Pilot Study - PET Guidance I

Study Overview
=================
Brief Summary
-----------------
The aim of this single-center randomized controlled trial is to assess clinical usefulness of positron emission tomography combined with computed tomography (PET CT) in the diagnostic process of suspected cardiovascular implantable electronic device (CIED) infection (lead dependent infective endocarditis, generator pocket infection, fever of unknown origin).

Detailed Description
-----------------
Cardiovascular implantable electronic device (CIED) infection is a complication of increasing incidence. The prevalence of CIED infection is estimated at 2%, with differences between authors ranging from 0.13% to 19.9%. According to European Heart Rhythm Association survey conducted in high volume centers prevalence of CIED infections was below 2%. The majority of centers were able to isolate the infectious agent in ≤50% of blood cultures which underscore the difficulty in finding the agent of CIEDs infection in many cases. Cardiovascular implantable device infections can be categorized into 3 groups: superficial skin infection, generator pocket infection and intravascular infection with intact generator pocket. Although local pocket infection is the most common clinical infection occurring early after implantation, positive blood cultures may be the only sign of late onset intravascular infection Mortality in cardiovascular implantable electronic device related infective endocarditis treated with antibiotics only reaches 66%, whereas with combined therapy (antibiotics and complete device removal) it is 3-fold lower. Prolonged targeted antibiotic therapy (4 to 6 weeks) with complete device removal and revision of indications for re-implantation is recommended in most cases (class I with confirmed diagnosis and IIa with probable diagnosis). In complicated and uncertain cases additional diagnostic tools are needed, especially if we take into account the load of the patient associated with device removal, prolonged hospitalization and re-implantation. Apart from morbidity and mortality, infections are also associated with significant financial cost for patients and third-party payers. Polish data on this issue are not available yet but in US the estimated average cost of combined medical and surgical treatment of CIED-related infection ranges from USD 25,000 for permanent pacemakers to USD 50,000 for implantable cardioverter-defibrillators. Positron emission tomography combined with computed tomography (PET CT) can play an important role in difficult cases of CIED-related infections but published studies focused on the outcomes and safety of this procedure only briefly considering the economical aspect of this diagnostic test. Recent studies show that PET CT scan is effective and precise tool that can facilitate diagnostic process and decision making regarding therapy especially in difficult patients with CIED-related infections. PET CT scan can protect patients from unnecessary device removal or from too late removal. PET CT may also help in diagnosing other sources of infection, embolic complications, neoplasms, autoimmune diseases and connective tissue diseases. However there are some issues concerning low sensitivity connected with elevated marker uptake in myocardium and in case of small vegetations, especially lead-related In most studies assessing PET CT in diagnostic process of CIED related infections standard oncologic protocols were used. Those protocols may not be optimal to assess FDG uptake by inflammatory cells. The aim of this single-center randomized controlled trial is to assess clinical usefulness of positron emission tomography combined with computed tomography (PET CT) in the diagnostic process of suspected cardiovascular implantable electronic device (CIED) infection (lead dependent infective endocarditis, generator pocket infection, fever of unknown origin). All patients participating in the study will undergo standard diagnostic process. Conventional/standard diagnostic and therapeutic process will consist of: medical interview, physical examination, laboratory tests, blood cultures (3 sets, 1 hour apart, repeated after 24 hours and -if applicable - with fever peak above 38°C); imaging studies (echocardiography: transthoracic, and if there are no contraindications transesophageal, in case of negative or equivocal result repeated after 7-10 days, or in series if necessary, computed tomography scan for pulmonary embolism if indicated); if there are abnormalities in other systems, decisions concerning further diagnostics will be made by the physician in charge. Apart from standard diagnostic procedures patients will undergo whole body PET CT scan to localize infection or inflammation. Then the investigators team will make a decision concerning further treatment (antibiotics and complete device removal vs conservative treatment).

Official Title
-----------------
Positron Emission Tomography Combined With Computed Tomography (PET CT) in Suspected Cardiovascular Implantable Electronic Device Infection, a Pilot Study - PET Guidance I

Conditions
-----------------
Complications, Infective Endocarditis, Implant Site Pocket Infection, Fever of Unknown Origin

Intervention / Treatment
-----------------
* Other: PET CT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age - 18 years and older. Written informed consent for participating in the study and written standard version of informed consent for PET CT scan. Suspected generator pocket infection Suspected cardiovascular implantable electronic device (CIED)-related infective endocarditis Fever of unknown origin in patient with CIED Exclusion Criteria: Lack of written informed consent Pregnancy or breast feeding Inability to stay supine for the time of PET CT scan Unstable cardio-pulmonary state Glucose level above 200 mg/dl

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CIED related infection<br>All patients will undergo standard diagnostic process that will consist of: medical interview, physical examination, laboratory tests, blood cultures (3 sets, 1 hour apart, repeated after 24 hours and -if applicable - with fever peak above 38°C); imaging studies (echocardiography: transthoracic, and if there are no contraindications transesophageal, in case of negative or equivocal result repeated after 7-10 days, or in series if necessary, computed tomography scan for pulmonary embolism if indicated); if there are abnormalities in other systems, decisions concerning further diagnostics will be made by the physician in charge. Apart from standard diagnostic procedures patients will undergo whole body PET CT scan to localize infection or inflammation. Then the investigators team will make a decision concerning further treatment (antibiotics and complete device removal vs conservative treatment). | Other: PET CT<br>* All patients are examined by a physicians before PET CT and if there are no contraindications they are given isotope intravenously. Then they stay in a warm waiting room. The dose of 18-FDG depends on patient's weight and varies from 270 to 420 MBq. Isotope uptake time is about 45-180 minutes. After that time the patient is asked to empty his or her bladder and go to the examination room. First CT scan lasting 2 min is performed followed by the PET scan lasting about 20 min. Usually area from mid tigh to eye level is scanned. In PET we use iterative reconstruction method (number of subsets 28, number of iterations 2), time of acquisition in one position of a table - 2 minutes. The following parameters will be analyzed: standardized uptake value (SUV) in the CIED area (pocket, leads), SUV of vascular background - pulmonary trunk, SUV of a liver, SUV max. in other potential changed areas, volume with increased SUV> 40% of the background.<br>* Other names: Positron emission tomography - computed tomography;|
| Non-infective<br>Control group consisting of 20 pts with implanted CIEDs who underwent PET CT due to non infectious indications and have no data for infectious process in follow-up | Other: PET CT<br>* All patients are examined by a physicians before PET CT and if there are no contraindications they are given isotope intravenously. Then they stay in a warm waiting room. The dose of 18-FDG depends on patient's weight and varies from 270 to 420 MBq. Isotope uptake time is about 45-180 minutes. After that time the patient is asked to empty his or her bladder and go to the examination room. First CT scan lasting 2 min is performed followed by the PET scan lasting about 20 min. Usually area from mid tigh to eye level is scanned. In PET we use iterative reconstruction method (number of subsets 28, number of iterations 2), time of acquisition in one position of a table - 2 minutes. The following parameters will be analyzed: standardized uptake value (SUV) in the CIED area (pocket, leads), SUV of vascular background - pulmonary trunk, SUV of a liver, SUV max. in other potential changed areas, volume with increased SUV> 40% of the background.<br>* Other names: Positron emission tomography - computed tomography;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with established diagnosis | Standardization of PET CT in diagnostic process of local infections and lead dependent endocarditis in clinical practice. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of the diagnosis held by PET CT compared with final clinical diagnosis | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with remote infective complications | Assessment of usefulness of PET CT for detection of remote infective complications (metastatic abscesses, infected pulmonary emboli) | up to 6 months | 
| Number of participants with particular localizations of infection | Incidence of particular localizations of infection | up to 6 months | 
| Number of participants with sustained therapuetic decision | Influence of PET CT on therapeutic decision: confirmation or change of decision based on PET CT (percentage) | up to 6 months | 
| Number of participants with complications of PET CT | Safety and complications of diagnostic process of CIED related infections with PET CT | up to 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Positron emission tomography combined with computed tomography, PET CT, Cardiovascular Implantable Electronic Device, Infective endocarditis, Generator pocket infection, Fever of unknown origin