Nuclear cardiology – Current status of the clinical application.

Abstract

This updated position paper from the German Society of Nuclear Medicine (DGN) and the German Cardiac Society (DGK) replaces the original statement from 2018. It gives an overview of the fields of application and the current value of nuclear cardiological imaging. The topics covered include chronic coronary syndrome, including viability diagnostics and the special value of positron emission tomography (PET), cardiomyopathies, cardiac sarcoidosis, amyloidosis, infectious endocarditis and inflammation of cardiac implants.

Keywords

Chronic coronary syndrome - Positron emission tomography - Single photon emission computed tomography - Nuclear medicine - Endocardial diseases

Preamble

This position paper of the Working Group “Cardiovascular Nuclear Medicine” of the German Society for Nuclear Medicine (DGN) and the Working Group 20 “Nuclear Cardiological Diagnostics” of the German Cardiac Society (DGK) updates the joint statement from 2018 [1]. It summarises the current practical state of knowledge on nuclear cardiological diagnostics and is intended to make decision-making easier for doctors and patients. The position paper does not replace an individual medical evaluation, nor the adaptation of diagnostics and therapy to the patient’s specific situation or a guideline.

Introduction

This position paper is based on the existing national and international guidelines and scientific publications [3] [4] [5] [6] [7]. The nuclear cardiology principles and methods are published in current German and European guidelines and are not the subject of this paper [6] [8].

For better readability, the term “myocardial SPECT” is used for myocardial perfusion SPECT (SPECT – “single-photon emission computed tomography”).

In addition to this method, there is a wide range of nuclear cardiology examinations, both established and more recent, available for SPECT as well as for positron emission tomography (PET), using different radiopharmaceuticals [9]. The main areas of application of these studies are outlined below.

Diagnostics of chronic coronary syndrome (CCS)

Myocardial SPECT for the assessment of myocardial perfusion represents the most commonly used nuclear cardiology modality for ischaemia diagnostics, particularly at the level of outpatient specialist care [10]. Approximately 70% of all examinations are requested by cardiology, as survey results from recent years show [10]. From 2018 to 2024, the number of examinations increased by 36% (communication from the National Association of Statutory Health Insurance Physicians (KBV) made via the German Nuclear Medicine Association; publication in preparation, as of August 2025).

Standard myocardial SPECT includes:

• selection of the individually appropriate stress testing procedure (ergometric or pharmacological, the latter with the vasodilators adenosine or preferably regadenoson) to increase myocardial perfusion,

• ECG-triggered acquisition to determine left ventricular ejection fraction (LVEF),

• determination of semi-quantitative scores or percentages to estimate the extent and severity of the ischaemic burden and resting perfusion defects.

Detailed protocols, including the benefits and drawbacks associated with the study, as well as the specific indications and contraindications, can be found in the current national S1 guideline on myocardial SPECT [6].

Suspected chronic coronary syndrome including ANOCA/INOCA

Formally, the decision for non-invasive imaging is based on suspected (epicardial) obstructive stable coronary artery disease (CAD) as a cause of thoracic symptoms, including exertional dyspnoea at pre-test probabilities (PTP) of 15 to 85% [3] [7]. In general, testing with sensitivities and specificities of 70–80% in this field has the best diagnostic gain.

The individual PTP for stenosing CHD can be determined based on tables which take into account symptoms, age, gender, risk factors and additional pathological findings (e.g. ECG abnormalities, impaired LVEF, ventricular arrhythmias or PAD) [3] [7].

In the PTP range of 15 to 50%, CT coronary angiography is preferred. This was included in the EBM (Doctorsʼ Fee Scale) services catalogue on 01.01.2025. The EBM performance text explicitly calls for a PTP of 15–50% for performing CT coronary angiography. Alternatively, functional procedures such as stress echocardiography, cardiac MRI or myocardial SPECT may be used in this area [3].

The algorithm of the ESC guideline provides for the sequential use of CT coronary angiography and functional procedures and vice versa. This is the case with ambiguous results that do not sufficiently explain clinical symptomatology, for example.

At the macrovascular level, not only high-grade flow-limiting stenoses, but also diffuse atherosclerotic changes without apparent stenoses or structural abnormalities (muscle bridges, coronary abnormalities, or vasospasms) may be the cause of ischaemia detected by myocardial SPECT.

Coronary microcirculation dysfunction plays an important role at the peripheral vascular level. Functional and structural dysfunction of microcirculation can cause angina pectoris and ischaemia in the absence of significant stenosis of the epicardial coronary arteries: ANOCA (angina with no obstructive coronary disease) or INOCA (ischaemia with no obstructive coronary disease) [7].

In such constellations, the combination of morphologic and functional imaging is useful and diagnostically valuable. INOCA alone affects approximately 50–70% of women and approximately 30–50% of men [11].

Meta-analyses show that the diagnostic precision of the functional imaging procedures is comparable and that none of these imaging procedures is clearly preferable in this context [3]. Criteria for or against a particular non-invasive imaging modality include the patient’s situation and suitability, local availability and expertise [3]. Stress echocardiography and myocardial SPECT are currently (as of August 2025) the only ischaemia imaging tests that are embedded in the German statutory health insurance system (GKV) and remunerated.

The extent and severity of ischaemia (ischaemic burden) and resting perfusion defects can be measured in absolute or percentage terms in myocardial SPECT with scores (Summed Stress Score, Summed Rest Score and Summed Difference Score) ([6]; [Fig. 1]). Patients with a summed difference score >8 or an ischaemic burden ≥10% of the left ventricular myocardium generally benefit more from revascularisation than from optimised drug therapy alone in terms of prognosis improvement [12]. The underlying data are based on long-standing standardised use of myocardial SPECT in large cohorts [13]. The ischaemic burden of ≥10% should be considered an indicative threshold. The approach must always be coordinated individually between treating physicians and patients.

Fig. 1 Pathological myocardial SPECT with quantification of ischaemic burden. Top: Stress and resting perfusion. Exercise-induced ischaemia of the medial anterior wall to the inferoapical and within the apical septum. High Summed Stress Score (SSS = 13), low Summed Rest Score (SRS = 1) and high Summed Difference Score (SDS = 12), corresponding to an ischaemic burden of > 10% of the left ventricular myocardium. Bottom: The triggered study demonstrates a normal left ventricular ejection fraction (LVEF) at rest, and a markedly reduced LVEF under stress, indicative of transient ischaemia-related dysfunction, with hypokinesia in the apical, supra-apical, and septal regions. (With kind permission from the 2025 Institute of Radiology, Nuclear Medicine and Molecular Imaging, HDZ-NRW).

Known CHC

The evidence for the use of imaging techniques (including myocardial SPECT) in patients with known obstructive coronary artery disease or following an intervention (stent or bypass surgery) is insufficient [6]. Current recommendation and clinical practice both favour the use of non-invasive imaging in cases of clinical suspicion of disease progression.

If a prior examination has been performed using a non-invasive imaging method for comparability, the same imaging method should be repeated [3] [6].

Viability assessment

In the presence of regional and/or global impaired myocardial contraction, viability should be assessed before revascularisation, since only viable myocardium has the potential for recovery. Even if the LVEF does not improve after the intervention, patients can still benefit through the reduced risk for arrhythmia, infarction, and progression of heart failure and improved perfusion [14].

The focus of non-invasive imaging is to identify viable myocardial segments that are amenable to revascularisation. It cannot be reliably concluded from current evidence that patients with nonviable myocardial segments do not benefit from revascularisation [14].

¹⁸F-FDG-PET demonstrates higher accuracy than myocardial SPECT using ^99mTc perfusion radiopharmaceuticals for the assessment of viability and, when available, should be considered the nuclear cardiology method of choice for patients with markedly reduced LVEF (<30–40%) [10] [15]. The superiority of ¹⁸F-FDG-PET is based on the direct detection of metabolically active, yet ischaemically compromised viable myocardium (hibernating myocardium, myocardial “stunning”) [16].

Due to the dietary preparation required for ¹⁸F-FDG viability PET to ensure optimal radiopharmaceutical uptake, the procedure is challenging and time-consuming in patients with diabetes, particularly those with insulin resistance. Therefore, widespread use of ¹⁸F-FDG PET in this patient population is limited. A general consideration in PET viability imaging is the need to combine it with resting perfusion imaging to adequately distinguish hibernating or stunned myocardium from normally metabolically active myocardium.

Another limitation is that ¹⁸F-FDG PET for viability assessment is not covered by the GKV, even for this important indication.

Indications for nuclear medicine viability assessment are listed in [Table 1] [12] [17].

Table 1 Indications for viability assessment [17].

Evaluation of potential revascularisation strategies in patients presenting with heart failure, regional wall motion abnormalities, and a reduced left ventricular ejection fraction (typically <35%)	ESC level of recommendation class IIb, evidence level B
Assessment of the optimal revascularisation strategy (PCI or bypass surgery) in patients with complex multivessel coronary artery disease	No level of recommendation
Assessment of PCI versus medical therapy in chronic total occlusions (CTO)	No level of recommendation
Assessment of secondary PCI (PCI sometime after an acute coronary syndrome) in patients with heart failure	No level of recommendation
Assessment of mitral valve replacement with concomitant revascularisation versus isolated mitral valve treatment (repair, replacement, or mitral clipping) in patients with ischaemic mitral regurgitation (LVEF <30%)	ESC level of recommendation class IIa, evidence level C

Special status of cardiac PET

Cardiac PET occupies a special position in the diagnosis of chronic coronary syndrome in Germany, as it is more accurate than myocardial SPECT, yet is still not included in the GKV benefits catalogue. The situation in Switzerland is particularly notable, where more than half of myocardial perfusion studies are performed with PET [18].

The most significant diagnostic advantage of PET over other functional methods, is its ability to non-invasively quantify myocardial blood flow, allowing an evaluation of microcirculation and associated symptoms (ANOCA/INOCA).

PET also provides better image quality than SPECT in terms of resolution and contrast. PET radiopharmaceuticals also have more favourable flow properties (higher extraction rates) than SPECT radiopharmaceuticals.

In the ESC guideline, in patients with suspected CCS at the pre-test probability range of 15–85%, perfusion PET is assessed with a Class I, Level B recommendation and is favoured over myocardial SPECT for the reasons mentioned above [7].

The FDA has recently approved F-18-flurpiridaz for quantitative cardiac perfusion imaging with PET. The review by the EMA is currently ongoing (as of August 2025). Cardiac PET is expected to play an increasingly important role in the future.

Cardiomyopathies

One indication for imaging-based nuclear cardiology modalities arises in the diagnosis and treatment of cardiomyopathies, both in distinguishing ischaemic from non-ischaemic cardiomyopathy and in viability assessment [19].

The diagnosis of cardiomyopathies should include objective evidence of a microvascular origin. For the nuclear medicine perfusion diagnosis of ischaemic cardiomyopathies, PET with concurrent quantitative perfusion measurement, if available, is recommended in place of SPECT for the reasons outlined in the subchapter “Cardiac PET”.

In Germany, ¹³N-ammonia is generally available for PET perfusion, while ¹⁸O-water available at select centres. Other PET perfusion radiopharmaceuticals are currently under regulatory review and being evaluated in studies.

Sarcoidosis

One area of application of ¹⁸F-FDGPET-CT within a multimodal imaging concept is the evaluation of sarcoidosis. Indications include

• suspected cardiac involvement in patients with known extracardiac sarcoidosis with symptoms (unexplained syncope, presyncope, palpitations and/or abnormal ECG and/or unclear echocardiography),

• suspected recurrence in known cardiac sarcoidosis,

• monitoring of cardiac sarcoidosis therapy; and

• prognostic assessment to guide treatment decisions and assess progression [20] [21] [22].

¹⁸F-FDG-PET-CT is particularly useful for detecting the extent of involvement and the activity of the disease. It demonstrates high sensitivity (94–100%) to thoracic disease and may help detect metabolic activity in affected tissues.

In contrast to viability assessment using ¹⁸F-FDG, a dietary suppression protocol (“low carb”, “high fat”, “long fasting”, and, if necessary, intravenous administration of unfractionated heparin) is essential to suppress physiological myocardial metabolism to selectively visualise the immune cell metabolism of sarcoidosis-associated cardiac infiltrates [22].

Since routine whole body images are taken, sometimes with cardiac focus, extracardiac organ involvement can be detected without additional examination and radiopharmaceutical requirements ([Fig. 2]). Due to the physiologically high ¹⁸F-FDG uptake in the brain, this method does not allow reliable detection of cerebral sarcoidosis lesions.

Fig. 2 Sarcoidosis with cardiac involvement. Full-body imaging in sarcoidosis with suspected cardiac involvement using ¹⁸F-18-FDG-PET-CT. Patient with multiple sarcoidosis lesions, including myocardial involvement. Images acquired under a suppression protocol (overnight fasting, carbohydrate-free, high-fat diet the day before). (a) Whole-body images, (b) Cardiac cross-sectional images. (With kind permission from the 2025 Institute of Radiology, Nuclear Medicine and Molecular Imaging, HDZ-NRW).

In addition to ¹⁸F-FDG, ⁶⁸Ga-labelled somatostatin analogues such as DOTATATE (or DOTATOC or DOTANOC) offer a diagnostic alternative. These bind specifically to somatostatin receptors expressed on activated immune cells [23]. This can improve the detection of inflammatory lesions. Moreover, due to the lack of physiological myocardial uptake of these radiopharmaceuticals, dietary preparation of patients is not required. However, ⁶⁸Ga-labelled somatostatin analogues exhibit lower sensitivity and poorer performance in therapy monitoring than ¹⁸F-FDG [23].

For the assessment of possible or already diagnosed cardiac sarcoidosis, combined use of ¹⁸F-FDG PET with cardiac MRI as a simultaneous hybrid procedure provides additional information and can increase diagnostic accuracy [24].

MRI can detect both focal myocardial fibrosis and inflammation using late gadolinium enhancement (LGE) and diffuse myocardial changes. Simultaneously conducted ¹⁸F-FDG-PET provides precise co-registration of metabolic information from PET with tissue characterisation obtained from the MRI. This hybrid method thus allows not only the detection of cardiac sarcoidosis, but also a further classification as focal versus diffuse as well as active versus chronic processes [24].

Amyloidosis

In recent years, cardiac amyloidosis has gained increasing clinical attention as a systemic disease with myocardial involvement. In cardiac amyloidosis, nuclear cardiology, in addition to diagnosing cardiac function and infiltration by echocardiography or MRI, can provide important information on the type, severity, and progression of disease and help avoid endomyocardial biopsy [25] [26] [27].

Phosphate- and phosphonate-based radiopharmaceuticals used for conventional bone scanning show myocardial uptake in certain forms of cardiac amyloidosis, such as common wild-type transthyretin amyloidosis (wtATTR) and some hereditary variants. The exact underlying mechanism remains unclear.

The intensity of uptake is scaled using the Perugini score (0 to 3) [28]. A Perugini score of 1 does not exclude amyloidosis. In this case, further diagnostic evaluation should primarily aim to exclude light-chain amyloidosis (AL amyloidosis). A Perugini score of 2 or 3 in the absence of monoclonal light chains allows the non-invasive diagnosis of ATTR amyloidosis with high diagnostic certainty [28].

The radiopharmaceuticals ⁹⁹mTc-DPD (diphosphono-propano-dicarboxylic acid), ⁹⁹mTc-HMDP (hydroxymethylene diphosphonate) and ⁹⁹mTc-PYP (pyrophosphate) have been shown to be highly sensitive and specific for the diagnosis of ATTR amyloidosis. The ^99mTc-MDP (methylene diphosphonate) tracer, also used for skeletal scintigraphy, is not suitable [28].

As the aforementioned radiopharmaceuticals may also show uptake in cases of cardiac involvement in AL amyloidosis, determination of serum free kappa and lambda light chains and immunofixation in serum and urine are essential to differentiate and exclude a plasma cell disorder or AL amyloidosis [26].

Amyloid-targeted PET tracers (such as ¹⁸F-florbetapir, ¹⁸F-florbetaben, ¹⁸F-flutemetamol) developed specifically for Alzheimerʼs diagnosis are able to selectively detect amyloid in the myocardium. It can therefore be anticipated that they will make an important contribution in the future for indication selection and therapy monitoring of novel amyloid-targeted therapies [29].

Infectious endocarditis and cardiac implant inflammation

Alongside the less frequently used SPECT-CT with radiolabelled leukocytes, ¹⁸F-FDG PET-CT is the most important nuclear cardiology modality for the diagnosis of infective endocarditis. For questions regarding inflammation of prosthetic valves, both modalities, alongside positive blood cultures, are considered major criteria [4]. The combination of ¹⁸F-FDG-PET with contrast-based cardiac CT protocols is essential and shows significantly better diagnostic accuracy than “low-dose” CT without contrast [30].

Nuclear cardiology modalities demonstrate limited diagnostic accuracy for assessing inflammation of native valves and are therefore neither appropriate nor indicated in these cases. The reason for this is the small size of the structure, its motion, and often the presence of a biofilm, which blocks the cellular response and thus the imaging signal [31].

Inflammation diagnostics with ¹⁸F-FDG PET-CT are primarily indicated in patients with native valves to identify metastatic foci and/or the primary focus. The same applies to the expanded diagnostics of inflammation in patients with prosthetic valves [4].

Since ¹⁸F-FDG PET-CT is routinely performed as a whole-body scan, extracardiac sites of inflammation outside the brain can be detected without additional imaging or radiopharmaceutical use. Due to the physiologically high ¹⁸F-FDG uptake of the brain, it is not possible to reliably detect inflammatory foci in this organ.

¹⁸F-FDG-PET-CT exhibits high sensitivity but lower specificity compared with leukocyte SPECT, as the ¹⁸F-FDG signal reflects not only inflammatory responses (“uptake” in immune cells) but also non-inflammatory reparative processes and foreign body reactions (non-specific “uptake”). In contrast, leukocyte scintigraphy using SPECT with autologous, radiolabeled leukocytes is highly specific but less sensitive [4] [32] [33]. The use of this technique is recommended in cases of inconclusive ¹⁸F-FDG-PET-CT findings as part of a stepwise diagnostic approach, or in centres where PET-CT is not available [34]. In Germany, for logistical and regulatory reasons, leukocyte SPECT is now only carried out in a few centres.

It is important to stress that, given the often complex presentation of infective endocarditis, imaging findings should not be interpreted in isolation, but rather should be assessed and reviewed within a multidisciplinary endocarditis team [4].

¹⁸F-FDG PET-CT is also indicated for the assessment of inflammation after implantation of vascular grafts, pacemakers, defibrillators, and mechanical circulatory support devices ([Fig. 3]) [35].

Fig. 3 Positive amyloidosis findings. Skeletal scintigraphy (anterior and posterior projections) with dedicated cardiac imaging in a patient with ATTR amyloidosis (Perugini grade 3). No increase in urinary and serum light chains. Injection site: back of left hand. (a) whole body image, (b) cardiac SPECT-CT fused image. (With kind permission from the 2025 Institute of Radiology, Nuclear Medicine and Molecular Imaging, HDZ-NRW).

To assess cardiac inflammation with ¹⁸F-FDG-PET-CT, the use of a suppression protocol to suppress physiological myocardial uptake – similar to sarcoidosis protocols – is crucial for the selective detection and visualisation of inflammatory metabolic activity ([Fig. 4]).

Fig. 4 Endocarditis of a prosthetic aortic valve. Positive findings of prosthetic aortic valve endocarditis. PET (a), correlated CT layer (b), modality fusion (c). Images acquired under a suppression protocol (overnight fasting, carbohydrate-free, high-fat diet the day before). (a) Transverse PET slice, (b) Corresponding CT slice, (c) PET-CT fused image. (With kind permission from the 2025 Institute of Radiology, Nuclear Medicine and Molecular Imaging, HDZ-NRW).

Potential examination risks and radiation exposure

As with invasive coronary angiography and CT angiography, nuclear cardiology procedures are associated with a (relatively low) level of radiation exposure to the patient. In comparison to other invasive and non-invasive modalities, the theoretically estimated risk from radiation exposure in nuclear cardiology procedures is substantially lower and is very favourably outweighed by the clinical benefit. The Federal Office for Radiation Protection (BfS) has set diagnostic reference values for the most frequently performed procedures, including those in nuclear medicine, and adherence is rigorously monitored by the medical boards of the Chambers of Physicians [36].

Conclusion for practice

Nuclear cardiology modalities remain a key component in evaluating perfusion and myocardial viability in chronic coronary syndrome, and in the diagnostic evaluation of amyloidosis, sarcoidosis, and endocarditis.

Following the integration of CT coronary angiography into the EBM benefits catalogue, a move towards morphology-based diagnostic strategies is anticipated in patients with a 15–50% pre-test probability of obstructive coronary artery disease. In patients with inconclusive findings, the adjunctive use of functional modalities, such as myocardial SPECT, may guide more precise pre-selection for invasive interventions. Furthermore, myocardial SPECT allows the differential diagnosis of INOCA in cases with unremarkable CT angiography, enabling the identification of this prognostically important condition, particularly in women without epicardial coronary stenoses.

Conflict of Interest

The authors' conflict of interest can be found online on the DGK website at http://leitlinien.dgk.org/ under the corresponding publication.

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Publication History

Received: 08 October 2025

Accepted: 27 October 2025

Article published online:
16 January 2026