Emerging Uses of Cardiac PET
Beyond detecting blocked arteries, cardiac PET is opening new doors — helping physicians see inflammation, infection, and rare infiltrative diseases of the heart that other imaging tests can miss.
A powerful tool for detecting inflammation of the heart
Cardiac PET is best known for evaluating blood flow and ischemia — but its ability to detect inflammation is opening the door to a new generation of diagnoses. Researchers and clinicians are increasingly using cardiac PET to identify conditions that inflame the heart muscle and surrounding tissues, including:
- Infiltrative diseases such as amyloidosis, sarcoidosis, and Fabry disease.1–3
- Cardiovascular infections, particularly those involving implanted material such as prosthetic heart valves, left ventricular assist devices (LVADs), and vascular grafts.3
These uses are at various stages of investigation — some are already established in clinical practice, while others remain emerging. Ongoing work focuses on three main areas:
- Developing novel radiotracers, including 11C-Pittsburgh Compound-B, Gallium-68-DOTA-Tyr3-octreotide, 124I-evuzamitide, and a new generation of Fluorine-18 tracers.1,2,4
- Refining protocols for using these tracers to diagnose specific conditions.
- Defining the clinical situations in which PET provides the greatest diagnostic value.
Cardiac PET for the Diagnosis of Infiltrative Diseases of the Heart
Infiltrative cardiomyopathies are conditions in which abnormal substances build up in the heart muscle. Cardiac PET can help detect these diseases earlier, monitor how they progress, and guide treatment.
Cardiac Sarcoidosis
Cardiac PET helps physicians both diagnose cardiac sarcoidosis and monitor the disease over time.
The 2024 American Heart Association Scientific Statement on the diagnosis and management of cardiac sarcoidosis calls PET “an integral tool” in the evaluation and management of this condition. While cardiac MRI is typically the first imaging test recommended, the AHA advises that cardiac PET be considered when:4
- Cardiac MRI is not readily available or is contraindicated.
- Cardiac MRI is inconclusive, or suspicion for cardiac sarcoidosis remains high despite a normal MRI.
Major international societies — including the Heart Rhythm Society, the World Association of Sarcoidosis and Other Granulomatous Diseases, and the Japanese Circulation Society — also incorporate characteristic PET findings into their diagnostic criteria for sarcoidosis.5–7
Beyond diagnosis, PET plays a key role in assessing how patients respond to treatment and whether therapy should be adjusted. And emerging radiotracers are actively being investigated for their potential to detect cardiac sarcoidosis even more accurately.1
Cardiac Amyloidosis
Several amyloid-targeted PET radiotracers are in development. When combined with cardiac PET, these tracers hold real promise for detecting cardiac amyloidosis earlier, tracking treatment response, and improving prognostication.
Newer amyloid-binding tracers can also overcome important limitations of the imaging tests currently used to diagnose amyloidosis — including echocardiography, cardiac MRI, and SPECT with technetium-99m pyrophosphate (PYP).
Where current imaging falls short
- Echocardiography — Cannot directly image amyloid deposits and cannot diagnose amyloidosis on its own. Characteristic findings can overlap with other cardiomyopathies, especially early in the disease.
- Cardiac MRI — Also cannot directly image amyloid burden and cannot reliably distinguish amyloid from other processes such as inflammation, edema, or fibrosis.
- SPECT with PYP — The best current test for transthyretin (TTR) amyloidosis and able to quantify amyloid burden. However, because the tracer also binds to bone, false positives and false negatives are possible. It also cannot diagnose AL amyloidosis or other rarer forms.
Emerging amyloid-binding PET tracers can address these gaps. As Kottam and colleagues note in their review of infiltrative cardiomyopathies, “PET imaging in CA is still in the initial stages of development, and further studies are warranted to validate its use and value in clinical practice.”1
Anderson-Fabry Disease
Anderson-Fabry disease is a rare inherited condition. A deficiency of the enzyme alpha-galactosidase A leads to the buildup of glycosphingolipids in organs and blood vessels, including the heart. Cardiac involvement is the leading cause of death in patients with Fabry disease, making imaging essential for diagnosis, risk stratification, and monitoring disease progression.1 Importantly, Fabry disease is treatable with enzyme replacement therapy.
Echocardiography and cardiac MRI remain the most commonly used imaging modalities. But cardiac PET has shown early promise for identifying and quantifying myocardial inflammation in patients with Fabry disease — and preliminary research suggests it can improve both disease staging and early detection. Additional work is underway to define how PET can best support the diagnosis and management of this rare condition.
References — Infiltrative Diseases
- Kottam A, Hanneman K, Schenone A, et al. State-of-the-Art Imaging of Infiltrative Cardiomyopathies: A Scientific Statement From the American Heart Association. Circulation: Cardiovascular Imaging. 2023;16(11):e000081. View Study →
- Romero Pabón AJ, Clerc OF, Vijayakumar S, Cuddy SAM, Dorbala S. Recent Advances in Positron Emission Tomography Radiotracers to Image Cardiac Amyloidosis. Current Cardiology Reports. 2024;26(11):1153–1162. View Study →
- Slart RHJA, Glaudemans AWJM, Gheysens O, et al. Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases. European Journal of Nuclear Medicine and Molecular Imaging. 2021;48(4):1016–1039. View Study →
- Cheng RK, Kittleson MM, Beavers CJ, et al. Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association. Circulation. 2024;149(21):e1197–e1216. View Study →
- Birnie DH, Sauer WH, Bogun F, et al. HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated With Cardiac Sarcoidosis. Heart Rhythm. 2014;11(7):1304–1323. View Study →
- Judson MA, Costabel U, Drent M, et al. The WASOG Sarcoidosis Organ Assessment Instrument: An update of a previous clinical tool. Sarcoidosis Vasc Diffuse Lung Dis. 2014;31(1):19–27.
- Sato K, Kawamatsu N, Yamamoto M, et al. Utility of Updated Japanese Circulation Society Guidelines to Diagnose Isolated Cardiac Sarcoidosis. Journal of the American Heart Association. 2022;11(13):e025565. View Study →
PET/CT for the Diagnosis of Cardiovascular Infections
While no longer strictly an “emerging” use, cardiac PET/CT for cardiovascular infections is still less established than its use for ischemia — and it is one of the fastest-growing applications of the technology.
Fluorine-18 fluorodeoxyglucose PET/CT (18F-FDG PET/CT) plays an increasingly important role in diagnosing and managing infections inside the heart and blood vessels — particularly those involving prosthetic material such as artificial heart valves, grafts, ventricular assist devices, pacemakers, and defibrillators.8
Because 18F-FDG PET/CT is highly sensitive to inflammation — and infections produce significant inflammation — it can identify infections that other imaging tests miss.
40+
original research studies published over the past decade establishing the accuracy of 18F-FDG PET/CT for cardiovascular infections.8
~20%
of all endocarditis cases involve prosthetic valves — where standard imaging is less sensitive and PET/CT adds critical value.8
15-40%
infection rate for ventricular assist devices, one of the areas where PET/CT is proving especially useful.8
How PET/CT helps clinicians
18F-FDG PET/CT plays several important roles in the evaluation of suspected cardiovascular infections, including:
- Characterizing the extent of infection.
- Localizing where infection is occurring.
- Identifying areas that transesophageal echocardiography (TEE) cannot image well — including prosthetic valves and conduits.
- Informing risk assessment.
- Ruling out endocarditis or intracardiac infection in patients with symptoms, particularly those with prosthetic valves.8
More than 40 original research studies and 6 meta-analyses published over the past decade have established the accuracy and high sensitivity of 18F-FDG PET/CT for diagnosis of cardiovascular infections.8
Why timely, accurate diagnosis matters
Cardiovascular infections carry a high risk of death and serious complications. Treatment often involves prolonged courses of antibiotics and, in many cases, removal of infected hardware — a complex and risky procedure. Delays in diagnosis can significantly increase the chance of death or long-term disability, making it critical to identify infection quickly and accurately.
Infection can be especially difficult to diagnose in patients with:
- Pacemakers and defibrillators — with a 12-month infection incidence of roughly 1%.
- Vascular grafts — with infection rates of 0.2%–6%.
- Ventricular assist devices — with infection rates of 15%–40%.
In each of these settings, 18F-FDG PET/CT can help clinicians pinpoint infection when other tests fall short.
The case of prosthetic valve endocarditis
Transesophageal echocardiography (TEE) remains the standard imaging test for infective endocarditis (IE) involving native heart valves and is highly sensitive and specific in that setting. But TEE is less sensitive for prosthetic valve endocarditis (PVE), which accounts for roughly 20% of all endocarditis cases — a share likely to grow as heart valve replacements, and particularly transcatheter aortic valve replacement (TAVR), become more common.
18F-FDG PET/CT is helping close that diagnostic gap.
What the guidelines say
Multiple international guidelines already recognize the role of 18F-FDG PET/CT in cardiovascular infection, including:
- The 2023 European Society of Cardiology (ESC) guidelines on infective endocarditis.
- The 2020 European Heart Rhythm Association international consensus document on cardiac implantable electronic device infections.
- The 2018 European Association of Nuclear Medicine (EANM) guidelines on imaging in infective endocarditis.8–11
In the United States, formal cardiovascular society guidance came later. In June 2024, “18F-FDG PET/CT and Radiolabeled Leukocyte SPECT/CT Imaging for the Evaluation of Cardiovascular Infection in the Multimodality Context” was published — the first multidisciplinary U.S. cardiovascular society effort to formalize guidance on when to use 18F-FDG PET/CT in cardiovascular infections.8
The consensus document, developed with the American Society of Nuclear Cardiology, the American College of Cardiology, the American Heart Association, the Heart Rhythm Society, the American Society of Echocardiography, and other groups, establishes preliminary appropriateness criteria and highlights the critical role of radionuclide imaging in diagnosing and managing cardiovascular infection.
“Further investigation is warranted to validate the recommendations of this consensus document and to provide the basis for revised guidelines on cardiovascular infection within the next few years.” — 2024 U.S. multidisciplinary consensus document8
The guideline authors note that important gaps in the literature remain and that continued research will shape the next generation of recommendations.
References — Cardiovascular Infections
- Bourque JM, Birgersdotter-Green U, Bravo PE, et al. 18F-FDG PET/CT and Radiolabeled Leukocyte SPECT/CT Imaging for the Evaluation of Cardiovascular Infection in the Multimodality Context. JACC: Cardiovascular Imaging. 2024;17(6):669–701. View Study →
- Delgado V, Ajmone Marsan N, de Waha S, et al. 2023 ESC Guidelines for the management of endocarditis. European Heart Journal. 2023;44(39):3948–4042. View Study →
- Signore A, Lazzeri E, Glaudemans AWJM. Infection and inflammation imaging standardization: the EANM guidelines. Clinical and Translational Imaging. 2018;6(4):253–255. View Study →
- Blomström-Lundqvist C, Traykov V, Erba PA, et al. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections. EP Europace. 2020;22(4):515–549. View Study →
Help expand access to cardiac PET
Join the Alliance
Add your voice to the coalition fighting for patient access.
Share Your Story
Help others understand why cardiac PET matters.
Contact Us
Reach out to learn more or get involved.
pfoster@cardiacpetalliance.com
Contribute to Cardiac PET PAC
Support the PAC advocating for reimbursement.