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Article

The Use of 18F-FDG-PET in Systemic Sclerosis with Myocardial Involvement: The Scleroderma Heart Study

by
Jamie Sin Ying Ho
1,
Thomas Wagner
1,2,
Christopher Denton
3,
John Gerry Coughlan
4,
Daniel Knight
4,5,6,
Tushar Kotecha
4,5,6 and
Benjamin Schreiber
4,7,*
1
Department of Nuclear Medicine, Royal Free Hospital, Royal Free London NHS Foundation Trust, London NW3 2QG, UK
2
Centre for Medical Imaging, Division of Medicine, University College London, London NW1 2BU, UK
3
Centre for Rheumatology and Connective Tissue Diseases, UCL Medical School, Royal Free Campus, London NW3 2QG, UK
4
National Pulmonary Hypertension Service, Royal Free London NHS Foundation Trust, London NW3 2QG, UK
5
Department of Cardiac MRI, Royal Free London NHS Foundation Trust, London NW3 2QG, UK
6
UCL Institute of Cardiovascular Science, University College London, London WC1E 6DD, UK
7
Division of Medicine, University College London, London WC1E 6JF, UK
*
Author to whom correspondence should be addressed.
Sclerosis 2025, 3(3), 31; https://doi.org/10.3390/sclerosis3030031
Submission received: 26 April 2025 / Revised: 13 August 2025 / Accepted: 12 September 2025 / Published: 18 September 2025
(This article belongs to the Special Issue Clinical Advances and New Insights in Systemic Sclerosis)
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Abstract

Objectives: Cardiac involvement in scleroderma due to myocardial inflammation and fibrosis is associated with poor outcomes, but there is lack of consensus on its investigation and treatment. In this prospective pilot study, we aimed to assess the cardiac uptake of 18F-FDG-PET/CT in suspected scleroderma cardiomyopathy. Methods: The Scleroderma Heart study involved 16 patients with cardiac scleroderma but no coronary artery disease. 18F-FDG-PET/CTs were performed, and the patients with a positive scan were offered a second 18F-FDG-PET/CT scan after 6–9 months. The clinical characteristics and clinical outcomes (all-cause mortality) were compared between the patients with positive and negative 18F-FDG-PET/CT scans. Results: Of the 16 included patients, 8 (50%) had positive myocardial uptake on the 18F-FDG-PET/CT, 2 of whom showed a pattern consistent with cardiac involvement in scleroderma, while 6 patients more likely had physiological uptake. Over a mean follow-up of 603.3 days, all-cause mortality occurred in six patients (37.5%), and the mortality was similar between the two groups. Five patients with repeat 18F-FDG-PET/CTs showed stable or increased FDG uptake despite immunosuppression. Conclusions: To the best of our knowledge, this is the first study to investigate 18F-FDG-PET/CT in scleroderma patients with suspected cardiac involvement. The cardiac PET showed limited clinical utility due to frequent physiological uptake and lack of correlation with the treatment response. Further studies with larger cohorts and standardised interpretation criteria are needed before cardiac PET can be recommended for routine clinical use in scleroderma cardiomyopathy.

1. Introduction

Scleroderma, or systemic sclerosis, is a connective tissue disease characterised by vascular dysfunction and fibrosis of the skin and internal organs, such as the lungs, kidneys, and gastrointestinal tract. Cardiac involvement has a clinical prevalence of 15–35%, and is responsible for up to 30% of scleroderma-related deaths [1]. Primary myocardial disease, also known as systemic sclerosis (SSc) cardiomyopathy, is poorly defined in previous studies and is often not differentiated from ischaemic heart disease or PAH, complicating our understanding of cardiac scleroderma [2]. Autopsy studies have found myocardial involvement in up to 80% of scleroderma patients, with fibrosis and inflammation in the myocardium [3,4]. However, this high prevalence of histological involvement contrasts with the lower rates of clinically significant cardiac disease. Clinically evident cardiac involvement, characterised by a reduced ejection fraction, heart failure symptoms, or significant arrhythmias, is associated with poor prognosis and increased mortality risk [2,5], whilst subclinical histological involvement may not carry the same prognostic significance.
The diagnosis of cardiac involvement in scleroderma remains challenging, and there is a lack of consensus on its investigation and treatment. Cardiac magnetic resonance imaging (CMR) may reveal the subtle functional abnormalities and diffuse biventricular changes in scleroderma [6]. Recent work has identified five distinct CMR-defined cardiac phenotypes in systemic sclerosis that are associated with different prognostic outcomes, highlighting the heterogeneous nature of cardiac involvement and the potential for more precision-based approaches to assessment and management [7]. However, CMR has been found to have only moderate sensitivity and specificity for confirming known cardiac disease in scleroderma, and the correlation of abnormalities detected with the treatment outcomes remains unknown [8]. The complexity of cardiac involvement in scleroderma is further compounded by the coexistence of multiple pathophysiological processes, including acute inflammation, progressive fibrosis, and microvascular dysfunction, which may respond differently to immunosuppression and require distinct therapeutic approaches [9]. Position emission tomography (PET) may assist in differentiating these disease processes, as inflammation of the heart may lead to uptake of 18-FDG localised by a PET/CT, but not quiescent fibrosis. Although the studies to date using 18-FDG PET to assess cardiac involvement in scleroderma have been limited [10], in other systemic diseases such as sarcoidosis, it has demonstrated utility in diagnosing and monitoring cardiac disease after treatment [11]. Therefore, we hypothesise that 18-FDG-PET/CT may aid in assessment of patients thought to have heart muscle involvement from scleroderma.
In this prospective pilot study, we aimed to assess the uptake of 18-FDG-PET/CT in the hearts of patients with suspected cardiac scleroderma. We also investigated the prognostic significance of 18-FDG uptake in the heart and assessed the changes in uptake with medical treatment.

2. Methods

2.1. Study Design

The Scleroderma Heart study was a pilot study involving prospective recruitment of patients with scleroderma and suspected cardiac involvement at the Royal Free Hospital, London, UK, from November 2017 to October 2021. The study was approved by the research ethics committee and all patients provided written informed consent. The full study protocol is available in the Supplementary Material, and the trial is registered on the ISRCTN Registry (ISRCTN55643149).

2.2. Patient and Public Involvement

The patients and public were involved via a collaboration with the Royal Free Charity. We intend to disseminate the results to the trial participants and seek their input on the appropriate methods for release of results to patients and the public.

2.3. Patient Eligibility

The inclusion criteria were adult patients (1) who met the American College of Rheumatology diagnostic criteria for scleroderma [12], (2) with suspicion of cardiac involvement, and (3) no coronary artery disease. The broad inclusion criteria for suspected cardiac involvement were deliberately chosen to capture the heterogeneous spectrum of cardiac involvement in scleroderma, as previous studies have shown that isolated troponin elevation and arrhythmias can be early manifestations of scleroderma cardiomyopathy, in the absence of overt left ventricular dysfunction. Suspicion of cardiac involvement was defined as one or more of the following: an LVEF < 40% on an echocardiogram, abnormal heart muscle tissue characterisation on a CMR, diastolic heart failure without known risk factors (age < 50 years, no known systemic hypertension, no diabetes mellitus, and pulmonary arterial wedge pressure > 15 mmHg on right heart catheterisation at rest), persistently raised troponin without coronary artery disease, and ventricular arrhythmias. Ischaemic heart disease was excluded by a CT coronary angiogram, myocardial perfusion scanning, dobutamine stress echocardiogram, or invasive coronary angiography.

2.4. Data Collection

The patient data were collected from the electronic medical records and pre-designed Case Report Forms (CRFs) during each patient visit. As part of standard clinical care, a full cardiac evaluation was undertaken, which included a rheumatic and cardiac history and examination, blood tests, six-minute walking distance, ECG, and echocardiogram. An endomyocardial biopsy (EMB) was performed in selected scleroderma patients with heart involvement at the discretion of the treating clinician and patient. Patients with evidence of scleroderma cardiomyopathy were treated as per standard care.

2.5. 18F-FDG-PET/CT Protocol

An FDG PET was performed within 6 weeks of initial evaluation and registration into the study, and patients with a positive scan were offered a second 18F-FDG-PET/CT scan after six months of treatment [13].
For the 18F-FDG-PET/CT scan, patients were injected with 3 MBq/kg of 18F-FDG and rested for 60 min, after which full-body emission scans were performed. Following this, a low-dose scout CT and a low-dose CT were performed from the base of the skull to the mid-thigh to plan the bed positions for the whole-body emission scan. After the half-body acquisition emission scan, a dedicated acquisition of the heart was performed to allow for attenuation correction of PET images and localisation of tracer uptake. A PET cardiac acquisition was performed for 10 min.
The maximum standardised uptake value (SUVmax) in areas of increased uptake and in the septum were measured, and reported as positive or negative for heart involvement by a single Nuclear Medicine consultant physician who was blinded to the study outcomes. Due to the lack of standardised criteria and validation of cardiac FDG uptake in cardiac scleroderma, patients were categorised as positive or negative based on the visual pattern of tracer uptake. To assess the results of cardiac PET independently of other investigations, the reporting of cardiac PET was performed blinded to the results of CMR, echocardiography, and serological tests.

2.6. Study End Points

The aim of this exploratory study was to assess whether FDG PET can detect inflammation in the heart of scleroderma patients with suspected cardiac involvement based on the criteria stated above. The primary end points were to assess uptake of 18F-FDG-PET/CT in the heart of patients with known cardiac scleroderma, and compare the clinical characteristics and outcomes (all-cause mortality) of patients with positive and negative FDG PETs. The secondary end points were to assess the change in the cardiac FDG PET uptake in patients with positive scans after a change in immunotherapy.

2.7. Statistical Analyses

Statistical tests were performed using SPSS (Version 25, IBM Corp, Armonk, NY, USA). Patients with myocardial FDG uptake (positive PET) were compared to those without (negative PET). Categorical variables were presented as the frequency and percentage and compared using a chi-squared test or Fisher’s exact test as appropriate. The continuous variables were presented as the mean and standard deviation (SD) and compared using Student’s t test.

3. Results

3.1. Baseline Characteristics

A total of 19 patients consented, and 16 were included in our study cohort as 3 patients were excluded due to underlying coronary artery disease in one patient and no cardiac PET-CT performed in two patients (Figure 1). Five patients had a repeat cardiac PET scan; thus, a total of 21 PET-CT scans were performed. The baseline characteristics of the included patients are shown in Table 1 and Table 2. The mean age was 46.4 (SD 15.1) years and 37.5% (six patients) were male. All the patients had diffuse cutaneous systemic sclerosis, with a mean diagnosis duration of 5.36 (SD 5.15) years. All the included patients fulfilled one or more of the cardiac inclusion criteria, with 50% (seven patients) having abnormal heart muscle tissue characterisation on the CMR, 50% (seven patients) had persistently raised cardiac troponins, 7.1% (one patient) had diastolic heart failure with no known risk factors, and 7.1% (one patient) had ventricular arrhythmias.

3.2. Positive Versus Negative PETs

Of the 16 included patients, 8 (50%) had focal or diffuse tracer uptake on the cardiac PET and 8 (50%) had a negative scan. The characteristics of these two groups f patients are presented in Table 2. The pattern of uptake for these patients was diffuse in six patients, which may represent either diffuse myocarditis or physiological cardiac uptake, while two patients (cases 12 and 13) had cardiac PET scans consistent with cardiac involvement in scleroderma (Table 3).
The cardiac PET for case 12 demonstrated moderate uptake in the LV lateral wall, the base of anterior and inferior walls, and low-grade uptake in the base of septum and right ventricle (SUVmax overall 7.1; SUVmax septum 2.5) (Figure 2A). The patient also underwent a cardiac biopsy that showed patchy myocyte hypertrophy and fibrosis, which could be secondary to ischemia in the context of systemic sclerosis, but no active endocarditis or myocarditis. The CMR performed on this patient showed patchy epicardial focal fibrosis of the lateral wall.
Case 13 had moderate heterogenous LV enhancement, which was intense at the base of the anterior wall, and this patchy myocardial uptake may represent active myocarditis (SUVmax overall 7.4; SUVmax septum 4.2) (Figure 2B). The CMR, however, did not demonstrate any signs of cardiac involvement on T1 or T2.
Regarding the all-cause mortality over a mean follow-up of 603.3 days (SD 483.3), six patients died (37.5%), of whom four had cardiac uptake on the 18F−FDG−PET/CT (representing 50% of the group) and two patients did not (representing 25% of the group) (OR: 3.00; 95% CI: 0.36, 24.92; p = 0.608). Case 12 died after a follow-up of 2.3 years, while case 13 remained alive after a follow-up of 1.9 years.

3.3. Repeat Cardiac PETs and Immunosuppression During the Interval

Five patients had repeat PETs after a range of 182–284 days (mean 229 days; SD 41) (Table 4). All the patients had abnormal uptakes on the first and second cardiac PETs. Four patients had changes in immunosuppression during the interval. Case 7 started rituximab and hydroxychloroquine after the first abnormal cardiac PET, and their SUVmax was similar post-therapy (9.6 from 10.4). Her cardiac symptoms remained stable during the follow-up. Case 17 started MMF, and their SUVmax also remained similar (18 from 17.2), but they subsequently died. Cases 8 and 14 showed an increased SUVmax on their repeat cardiac PETs, despite starting or increasing immunosuppressants, such as cyclophosphamide, rituximab, and steroids. Case 8 died of persistent tachycardia and sudden death due to scleroderma cardiomyopathy as stated on the death certificate, while case 14 remained stable. Case 12 had an increased SUVmax (11 from 7.1) with no change in immunosuppression, but their repeat cardiac PET was more consistent with a physiological pattern of uptake. The patient then developed severe LV systolic failure and died during the follow-up.

4. Discussion

In this exploratory study, 50% of a cohort of scleroderma patients with evidence of cardiac involvement had myocardial uptake on an 18F−FDG−PET/CT, but only 12.5% had a definitely abnormal uptake pattern. This may have been due to physiological uptake of radioactive tracer in the myocardium, confounding the interpretation of the cardiac PET scans. However, we demonstrated that in some cases cardiac PETs may identify features of cardiac involvement not seen on other modalities, and may demonstrate changes in uptake patterns over time with treatment of scleroderma.
Myocardial fibrosis is an immunopathological hallmark of SSc cardiomyopathy [14]. Fibrosis may be due to the underlying microvascular disease in scleroderma, where intermittent vascular spasms, ischaemic necrosis, and reperfusion injury may lead to fibrogenesis [3]. Inflammation may also drive fibrosis, and this is supported by the increased pro-inflammatory cytokine interleukin-1 and tumour necrosis factor alpha levels in the bronchoalveolar lavage fluid and serum of SSc patients [15]. Myocardial inflammation has been proposed as responsible for early SSc cardiomyopathy, while fibrosis may occur in later stages [14]. The enhanced glycolysis in inflammatory cells (macrophages, lymphocytes, and monocytes) associated with acute inflammation may be identified on 18F−FDG PETs in connective tissue disorders [16], which may have therapeutic implications in SSc cardiomyopathy.
The use of 18F−FDG−PET/CT with appropriate suppression of physiological uptake in cardiac sarcoidosis is clinically established and there is increasing acceptance of its use in myocarditis [11]. 18F−FDG−PET/CT has good agreement with CMR and EMB for the diagnosis of myocarditis [17,18]. In a study of 16 scleroderma patients compared to nine control patients without cardiac symptoms by Besenyi et al., the scleroderma patients had a higher myocardial 18F−FDG SUV ratio on the 18−FDG−PET/CT than the controls [10]. Agoston et al. studied 17 patients with connective tissue disease (13 with systemic sclerosis) and found 29% had increased 18F−FDG activity, but only among those with systemic sclerosis and not giant cell arteritis [19]. We found that 50% of patients with scleroderma and evidence of cardiac involvement had a significantly increased 18F−FDG, higher than that found by Agoston et al. [19], which was expected in our population of patients with evidence of cardiac involvement on other modalities. A recent study of six SSc patients with and eight without myocardial fibrosis who underwent 68Gallium-labelled-Fibroblast Activation Inhibitor-04 ([68Ga]Ga−FAPI−04)-PET−CT showed that the [68Ga]Ga−FAPI−04 tracer uptake was higher in the patients with myocardial fibrosis [20]. This correlated with elevated serum NT−pro−BNP, arrhythmias, increased late gadolinium enhancement on a CMR, and sequential [68Ga]Ga−FAPI−04−PET−CT scans showing dynamic uptake that was associated with changes in the activity of myocardial fibrosis in SSc. This further provides evidence that PET−CTs may have potential use in SSc with myocardial involvement, and additional research is needed.
In our study, 12 patients had no pulmonary hypertension (PH), while one had borderline PH not consistent with the myocardial and right heart abnormalities (case 14). In a study of 56 patients with SSc of less than 5 years’ duration and normal pulmonary arterial pressure, SSc was associated with a significantly lower RVEF and peak filling rate than the controls [21]. The RVEF correlated with the LVEF but not with pulmonary function impairment or pulmonary arterial pressure [22]. The RV longitudinal strain and strain rate were also lower in SSc patients without PH than the controls, but no significant difference was found in the LV strain [23]. In scleroderma patients without cardiac symptoms, the association of elevation in 18F−FDG with the LV global longitudinal strain is conflicting. Besenyi et al. found no significant difference between PET-positive and -negative patients, while Agoston et al. found an inverse relationship in patients with systemic sclerosis [10,19]. We found that the LVEF at baseline and at follow-up was similar in patients with positive and negative PETs, and the correlation between the LV function and FDG uptake requires further investigation. Taken together with our finding of increased FDG uptake associated with RV systolic dysfunction, PETs may identify patients with myocardial involvement and resultant cardiac dysfunction.
Cardiac involvement in SSc is an important predictor of mortality. A meta-analysis of 18 studies on 12,829 patients reported that 19.7% of SSc patients died of cardiac causes, 13.1% died of PH, and cardiac involvement was associated with more than triple the risk of death compared to that for scleroderma patients without cardiac involvement [23]. On CMR, elevated T1 and a reduced LV global longitudinal strain was associated with an increased risk of death, which are measures of diffuse fibrosis [24]. Patients with SSc-associated myocarditis were at greater risk of death than those related to other systemic autoimmune diseases or isolated myocarditis, and those who died despite immunosuppressive therapy had higher fibrotic scores on EMBs [13]. The overall mortality was 37.5% in our cohort of patients, and there was no significant difference between the patients with and without myocardial tracer uptake on the cardiac PETs. This may be due to our study being underpowered for this outcome, and further larger studies are needed to determine the effect of active myocardial inflammation on prognosis.
Active myocardial inflammation may predict the response to immunosuppressive therapy. Prednisolone improved the LVEF in patients with SSc, and the lower the initial LVEF, the greater the improvement seen [25]. In six SSc patients with new-onset active myocarditis and one patient with chronic or borderline myocarditis on an EMB, immunosuppressive therapy, such as azathioprine, MMF, and cyclophosphamide, improved symptoms and lowered cardiac enzymes levels, suggesting that presence of myocarditis in early disease may be improved with immunosuppression [26]. In our study, only five patients had repeat cardiac PETs within 6–9 months and they showed a stable or increased SUVmax despite immunosuppression. Three patients had disease progression and died during the follow-up, while two patients remained stable. Based on our results, we are not able to conclude whether immunosuppression improved disease activity and correlated with the FDG uptake, but cardiac PETs may provide additional information to guide the clinical diagnosis and management of cardiac scleroderma.
Future studies should consider longer observation periods, combination imaging approaches including cardiac MRI and novel PET tracers targeting fibrosis (such as 68Ga−FAPI), and correlations with cardiac functional outcomes to better characterise the role of inflammation versus fibrosis in scleroderma cardiomyopathy.
Based on our findings, we cannot recommend cardiac FDG−PET as a routine diagnostic tool for cardiac scleroderma given the high rate of physiological uptake and limited correlation with clinical outcomes. However, cardiac PET may have potential utility in research settings to phenotype patients with suspected active myocardial inflammation, particularly when other imaging modalities are inconclusive. The challenge of distinguishing pathological from physiological uptake remains a significant limitation that requires further research and standardisation of interpretation criteria.

Limitations

This is a pilot study of 16 patients with cardiac involvement in scleroderma, and there are several limitations. Firstly, the small study population increases the risk of selection bias and several statistical analyses are underpowered. Our study demonstrates feasibility of detecting cardiac involvement using 18F−FDG−PET/CT in scleroderma, and multicentre studies may be needed to increase patient recruitment in the future. Only patients with suspected cardiac involvement based on other investigations were included; thus, asymptomatic patients with undetected cardiac scleroderma may have been missed. Secondly, it is challenging to interpret the significance of FDG uptake on cardiac PETs, in the context of a lack of evidence related to the investigation and treatment of cardiac scleroderma [27]. Although EMB is regarded as the gold standard for myocarditis, few patients underwent an EMB due to its invasive nature. Direct comparisons with CMR were not performed as not all patients had had a CMR performed at the time of the cardiac PET. With the serial cardiac PETs, we attempted to assess whether these scans could monitor the progression and response to therapy, but due to the small sample size we did not observe any patterns. Thirdly, there may have been false-positive FDG uptake on the PETs due to physiological uptake. To suppress physiological uptake, a high-fat low-carbohydrate diet and subsequent fasting was adopted, but this may not have been sufficient in some patients [28]. Alternative tracers (such as 68Ga-dotatate and 18F-fluorothymidine) that would not be subject to physiological uptake are being investigated; 68Ga-dotatate seems to be less sensitive than FDG [29], but 18F-fluorothymidine performed better than FDG for the detection of cardiac sarcoidosis [30]. This could be an avenue for research in cardiac scleroderma. Lastly, as most of the patients were on immunosuppression therapy during the study period, active myocardial inflammation may have been suppressed and not observed on the PETs. We therefore analysed the effect of change in immunosuppression on the repeat FDG uptake, but larger studies are needed to further characterise these findings.
As a pilot study in an understudied area, our findings should be interpreted as hypothesis-generating rather than definitive. The value of this work lies in establishing the feasibility of and identifying the key challenges in cardiac PET interpretation, and providing preliminary data to inform the design of larger multicentre studies.

5. Conclusions

In our exploratory study, 50% of scleroderma patients with cardiac involvement had myocardial uptake on an 18F−FDG−PET/CT, but the possibility of physiological uptake should be considered, and only 12.5% had patterns definitively consistent with scleroderma cardiac involvement. Five patients with repeat scans showed stable or increased FDG uptake despite immunosuppression, suggesting their limited utility for short-term treatment monitoring. In some cases, cardiac PETs may identify features of cardiac involvement in scleroderma, such as acute inflammation not seen on other modalities, and may demonstrate changes in uptake patterns over time, though the clinical significance remains unclear.
The effect of immunosuppression on cardiac FDG uptake and cardiac scleroderma in general requires further investigation with larger cohorts and longer follow-up periods. To the best of our knowledge, this is the first study to investigate the use of 18F−FDG−PET/CT in scleroderma patients with suspected cardiac involvement. Further validation studies with standardised interpretation criteria and correlation with histological findings are required before clinical implementation can be recommended.

6. Key Messages

6.1. What Is Already Known on This Topic

  • Cardiac involvement in scleroderma due to myocardial inflammation and fibrosis is associated with poor outcomes.
  • Existing techniques, such as echocardiogram and cardiac magnetic resonance imaging, only have moderate sensitivity and specificity for cardiac involvement in scleroderma.
  • The identification of cardiac scleroderma, prediction of active inflammation, and assessment of response to therapy remains challenging.

6.2. What This Study Adds

  • This is the first study to investigate the use of 18F−FDG−PET/CT in scleroderma patients with suspected cardiac involvement.
  • Fifty percent of scleroderma patients with cardiac involvement had myocardial uptake on an 18F−FDG−PET/CT, but only 12.5% had patterns definitively consistent with pathological involvement.
  • Repeat scanning showed limited utility for treatment monitoring, with stable or increased uptake despite immunosuppression.

6.3. How This Study Might Affect Research, Practice, and Policy

  • Cardiac 18F−FDG−PET/CT currently has limited clinical utility in scleroderma due to physiological uptake and a poor correlation with outcomes.
  • Future research should focus on alternative tracers, standardised interpretation criteria, and longer-term studies.
  • The findings provide important groundwork for future multicentre studies in this understudied area.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/sclerosis3030031/s1. Supplementary File: Study protocol. References [4,8,31,32,33,34,35,36,37,38,39,40,41,42,43] are cited in the supplementary materials.

Author Contributions

Conceptualization, T.W. and B.S.; methodology, J.S.Y.H., T.W., C.D., J.G.C., D.K., and B.S.; validation, B.S.; formal analysis, J.S.Y.H., D.K., and B.S.; investigation, T.W., C.D., J.G.C., T.K., and B.S.; resources, B.S.; data curation, J.S.Y.H., D.K., and B.S.; writing—original draft preparation, J.S.Y.H.; writing—review and editing, T.W., C.D., J.G.C., D.K., T.K. and B.S.; visualization, J.S.Y.H.; supervision, T.W. and B.S.; project administration, B.S.; funding acquisition, T.W. All authors have read and agreed to the published version of the manuscript.

Funding

Funding from the Royal Free Charity to cover cost of PET−CT scans performed in this study in the Nuclear Medicine Department is gratefully acknowledged.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Health Research Authority (REC reference 16/EM/0292 on 22 December 2016).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patient(s) to publish this paper.

Data Availability Statement

The raw data supporting the conclusions of this article will be made available by the authors on request.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Flow diagram of patient selection and investigation in the Scleroderma Heart study.
Figure 1. Flow diagram of patient selection and investigation in the Scleroderma Heart study.
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Figure 2. Typical images of positive PET scan for cardiac scleroderma: (A) case 12 and (B) case 13.
Figure 2. Typical images of positive PET scan for cardiac scleroderma: (A) case 12 and (B) case 13.
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Table 1. Patient-level characteristics of included patients.
Table 1. Patient-level characteristics of included patients.
No.Age (Years)SexEthnicityCo-MorbiditiesYears of DiagnosisOrgan InvolvementAntibodiesCardiac Signs and SymptomsTrop T (ng/L)NT Pro-BNP (ng/L)ECGEMBPETDeath
126FAsianNone7Raynaud’s, telangiectasia, digital ulcersANA, U3 RNPChest pain, palpitations22581SR, short PRNot attempted due to groin haematoma−N
232FWhiteSmall bowel bacterial overgrowth, inflammatory arthritis, migraines, IDA6NSIP, dysphagia, reflux and constipation, skin, myositis, Raynaud’s digital ulcersANA, ACA, Scl-70Chest pain, palpitations, presyncope, basal crackles41153SR, short PRNot performed as could not position catheter against RV−N
459FWhiteNarrow complex tachycardias, AF, diverticulosis4Immotile oesophagus, skin, Raynaud’s, digital ulcers, ILDANA, Scl-70None7269SR, LAD, RBBBN/A−N
535FBlackHTN3Severe pulmonary hypertension, myositis, NSIP, Raynaud’s, digital ulcers, GI involvementANA, Ro, Scl-70Chest pain, palpitations, raised JVP, basal crackles, peripheral oedema701196SR, RBBB, RVHN/A+Y
659MWhiteBifascicular block, latent TB on isoniazid1Extensive fibrotic NSIP, vasculitic rash, Raynaud’sANABasal crackles, peripheral oedema794SR, LAD, RBBBN/A−Y
761FBlackAF, bronchiectasis, OSA, obesity, asthma, hypothyroid, pulmonary HTN1NSIP, myositis, skin involvement, Raynaud’s, digital ulcers, GI involvementANA, ENA, Ro, Scl-70None146421NRFibrosis and focal myocarditis+N
Chest pain, syncope, peripheral oedema44NRSR, RBBB+
820MBlackSVT2Microstomia, myositis, myocarditis, Raynaud’s, digital ulcersANA, Scl-70, nRNPChest pain, palpitations6921207SRN/A+Y
Chest pain, orthopnoea, palpitations, raised JVP103889SR+
940FBlackDiscoid lupus5Myositis, Raynaud’sANA, U3 RNPPalpitations, peripheral oedema149211SR, LADNon-inflamed myocardium with mild interstitial fibrosis−N
1134FBlackNoneNRMyositis, mild ILD, digital ulcersANA, U3 RNP, Scl-70Chest pain, palpitations, raised JVP, peripheral oedema19181SRN/A−N
1256MWhiteHTN, hyperlipidaemia, COPDNRHeart, digital ulcersANAOrthopnoea, PND, palpitations, raised JVP383707Atrial pacedPatchy myocyte hypertrophy and fibrosis+Y
NRNRNR+
1346MWhiteRheumatoid arthritis, SLE overlap, sicca syndrome8Myocarditis, Raynaud’s, digital ulcersANA, PM-Scl, Ro, dsDNA, CCPNone838145SRN/A+N
1445MAsianTB lymphadenopathy1Myositis, sclerodactyly, synovitis, Raynaud’sANA, nRNP, Sm, Ro, KuNone190738SRN/A+N
NRNRNR+
1637MBlackHTN4Myositis, GORD, Raynaud’s, digital ulcersU3-RNP, ANANone16106SRN/A+N
1757FNRFamilial HTN, hypothyroidism, rectal Ca, migraines, CKD 3, sagittal sinus thrombosis, provoked PE20Renal crisis, Raynaud’s, digital ulcers, ILD, GI involvementANA, RNAP IIIPresyncope, peripheral oedema192614SR, LADNo evidence of myocarditis+Y
NRNRNR+
1866FWhiteHTN, hyperlipidaemia, asthma2Myositis, oral neuropathy, Raynaud’s digital ulcers, ILD, GI involvementANABasal crackles29214561HB, RBBB, LADMinor fibrosis, no myocarditis.−Y
1970FAsianHTN, IDA, glaucoma, mixed myelodysplastic/myeloproliferative disorder, CKD11Pulmonary hypertension, eczema, Raynaud’s, digital ulcers, ILD, reflux, renal crisisANA, RNAP IIIBasal crackles15405Sinus arrhythmiaN/A−N
Table 2. Characteristics of patients with positive versus negative cardiac PETs (n = 16).
Table 2. Characteristics of patients with positive versus negative cardiac PETs (n = 16).
VariableTotal (n = 16)PET + ve (n = 8)PET − ve (n = 8)MD (95% CI) or OR (95% CI)p-Value
Age (years)46.4 (15.1)44.6 (13.7)48.3 (17.1)−3.6 (−20.2, 13.0)0.647
Male (%)6 (37.5)5 (62.5)1 (12.5)11.7 (0.9, 147.6)0.119
Ethnicity
  White6 (40.0)2 (28.6)4 (50.0)-0.448
  Black6 (40.0)4 (57.1)2 (25.0)-
  Asian3 (20.0)1 (14.3)2 (25.0)-
Inclusion criteria
  LVEF < 40% on echo0 (0)0 (0)0 (0)--
  Abnormal heart muscle on cardiac MRI7 (50.0)3 (42.9)4 (57.1)0.56 (0.07, 4.67)1.00
  Diastolic heart failure with no known risk factors1 (7.1)0 (0)1 (14.3)-1.00
  Persistently raised troponin7 (50.0)4 (57.1)3 (42.9)1.78 (0.21, 14.77)1.00
  Ventricular arrhythmia1 (7.1)1 (14.3)0 (0)-1.00
Co-morbidities
  BMI (kg/m2)25.1 (5.3)26.0 (5.8)23.2 (4.5)2.8 (−3.1, 8.7)0.325
  HTN (%)7 (43.8)4 (50.0)3 (37.5)1.67 (0.23, 12.22)1.00
  T2DM (%)0 (0)0 (0)0 (0)-−
  Hyperlipidaemia (%)2 (12.5)1 (12.5)1 (12.5)1.00 (0.05, 19.4)1.00
  AF (%)2 (12.5)1 (12.5)1 (12.5)1.00 (0.05, 19.4)1.00
Symptoms
  Chest pain (%)5 (31.3)2 (25.0)3 (37.5)0.56 (0.07, 4.76)1.00
  Orthopnoea (%)1 (6.3)1 (12.5)0 (0)-1.00
  PND (%)1 (6.3)1 (12.5)0 (0)-1.00
  Palpitations (%)7 (43.8)3 (37.5)4 (50.0)0.60 (0.08, 4.40)1.00
  Presyncope (%)2 (12.5)1 (12.5)1 (12.5)1.00 (0.05, 19.36)1.00
  Syncope (%)0 (0)0 (0)0 (0)--
  Raised JVP (%)3 (18.8)1 (12.5)2 (25.0)2.33 (0.17, 32.58)1.00
  Basal crackles (%)5 (31.3)1 (12.5)4 (50.0)0.14 (0.01−1.76)0.282
  Peripheral oedema (%)5 (31.3)2 (25.0)3 (37.5)0.56 (0.07, 4.76)1.00
NYHA Class 2.75 (0.46)2.75 (0.71)0 (−0.64, 0.64)1.00
  Class I1 (6.3)0 (0)1 (12.5)-1.00
  Class II2 (12.5)2 (25.0)0 (0)-0.467
  Class III13 (81.3)6 (75.0)7 (87.5)0.43 (0.03, 5.99)-
Scleroderma involvement
  Myositis (%)9 (56.3)5 (62.5)4 (50.0)1.67 (0.23, 12.22)1.00
  Raynaud’s (%)14 (87.5)7 (87.5)7 (87.5)1.00 (0.05, 19.4)1.00
  Telangiectasia (%)1 (7.7)0 (0)1 (16.7)-0.462
  Digital ulcers (%)13 (81.3)7 (87.5)6 (75.0)2.33 (0.17, 32.58)1.00
  ILD (%)9 (56.3)3 (37.5)6 (75.0)0.20 (0.02, 1.71)0.315
  GI involvement (%)8 (50.0)4 (50.0)4 (57.1)0.75 (0.10−5.77)1.00
Duration of scleroderma (years)5.36 (5.15)5.57 (6.80)5.14 (3.34)0.43 (−5.81, 6.67)0.884
Serology
  Positive ANA (%)16 (100)8 (100)8 (100)--
  Positive ENA (%)10 (66.7)6 (85.7)4 (50.0)6.00 (0.48, 75.34)0.282
  Trop T (ng/L)160.1 (251.1)251.1 (325.4)69.0 (101.6)182.1 (−93.7, 458.0)0.168
  NT pro-BNP (ng/L)842.8 (1021.6)1266.8 (1275.0)418.8 (447.3)848.0 (−238.4, 1934.4)0.111
  CRP (mg/L)18.6 (21.7)21.4 (21.1)14.8 (24.0)6.5 (−19.8, 32.8)0.598
  CK (unit/L)541.1 (740.3)574.3 (578.3)508.0 (922.2)66.3 (−830,1, 962.7)0.875
  eGFR (mL/min)77.1 (19.1)80.9 (19.3)73.3 (19.4)7.6 (−13.1, 28.4)0.444
Fibrosis/myocarditis on biopsy (%) (n = 4)3 (75.0)1 (50.0)2 (100.0)-1.00
Cardiac PET
  SUV max overall6.7 (6.8)11.6 (6.7)1.8 (0.7)9.8 (4.2, 15.4)0.004
  SUV max septum4.9 (4.9)8.1 (5.1)1.6 (0.6)6.5 (2.2, 10.8)0.009
TTE LVEF baseline (%)59.3 (12.6)56.4 (14.4)62.1 (10.6)−5.7 (−19.3, 8.0)0.387
TTE LVEF 12 months (%)52.3 (15.9)55.9 (17.5)47.9 (14.4)8.0 (−13.8, 29.7)0.429
TTE LVEF follow-up (%)49.1 (13.1)52.0 (12.7)45.8 (14.1)6.2 (−12.1, 24.5)0.463
Decreased LVEF (>5%) in 1 year (%)6 (50.0)2 (28.6)4 (80.0)0.10 (0.01, 1.54)0.242
Time to 12 months TTE (days)334.8 (215.1)318.9 (213.4)357.0 (240.5)−38.1 (−331.2, 254.9)0.778
Decreased LVEF (>5%) on follow-up (%)6 (50.0)3 (42.9)3 (60.0)0.50 (0.05, 5.15)1.00
Time to last TTE (days)583.1 (482.0)466.7 (388.8)746.0 (596.0)−279.3 (−908.8, 350.2)0.346
Duration of follow-up (days)603.3 (483.3)522.4 (285.6)684.3 (635.6)−161.9 (−713.0, 389.2)0.526
Mortality (%)6 (37.5)4 (50)2 (25)3.00 (0.36, 24.92)0.608
Table 3. Features of cardiac scleroderma on PET.
Table 3. Features of cardiac scleroderma on PET.
No.No. of PET ScansOriginal ReportRe-Report by Blinded Single Nuclear Medicine Physician in This StudySUVmax OverallSUVmax Septum
51Increased uptake in the heart and intense uptake in the lateral wall, apex, and anterolateral papillary muscle. Cardiac uptake could represent cardiac involvement by scleroderma or physiologic myocardial uptake.Intense uptake in apex, lateral wall, and right ventricle. Moderate uptake in septum, anterior, and inferior walls. Indeterminate—likely negative.11.55
71Abnormal uptake in the heart with intense uptake in the base of septum and base of the lateral wall. More moderate uptake in the anterior aspect of the septum and lateral wall. Increased uptake in the LV papillary muscles. Could represent cardiac involvement by scleroderma.Intense in base of septum and lateral wall, moderate in remainder of lateral and septal walls, moderate in right ventricle, intense anterior to AP trunk; likely physiological uptake.10.410.3
2Diffuse intense heterogeneous uptake in the LV and low-to-moderate uptake in the anterior and lateral walls of the RV. Uptake not significantly changed compared to previous scan.Diffuse moderate uptake in left and right ventricles, greater than MBP. Likely not suppressed uptake; physiological rather than cardiac inflammation.9.69.6
81Diffuse moderate-to-intense uptake in the LV and low-grade uptake in RV; could represent active cardiac myositis.Moderate diffuse in left ventricle and low-grade in right ventricle; pattern likely physiological.7.45.5
2Intense diffuse homogeneous uptake in the LV and moderate diffuse homogeneous uptake in the RV; unchanged compared to previous scan.Intense diffuse in left and right myocardium; likely physiological.19.517.7
121Increased uptake in the LV, RV, and RA compatible with areas of inflammation due to cardiac involvement by scleroderma. Increased uptake in mediastinal nodes. Abnormal uptake in the larynx.Moderate in LV lateral wall, base of anterior and inferior walls, low-grade in base of septum and right ventricle. Indeterminate—likely positive.7.12.5
2N/AIntense diffuse in left myocardium and low-grade in right ventricle; likely physiological.118.2
131Patchy myocardial uptake in LV, may represent active myocarditis. Low-grade uptake in hilar lymph nodes is likely inflammatory.Moderate heterogeneous in left ventricle with intense in base of anterior wall. Indeterminate—likely positive.7.44.2
141Diffuse uptake in left and right ventricles; could be scleroderma myocarditis or physiological uptake.Moderate diffuse in left and right ventricles. Indeterminate—likely negative.6.26.2
2More intense uptake in the myocardium, diffuse and a reduction in disease activity elsewhere; likely physiological rather than worsening myocarditis.Intense diffuse in left ventricle; likely physiological.14.614.6
161No active infection or inflammation.Intense diffuse in left and right ventricles; likely physiological.25.615.2
171Diffuse intense increased tracer uptake throughout the LV myocardium in keeping with myocarditis.Intense diffuse homogeneous in left ventricle; indeterminate—likely physiological.17.216
2N/ASame intense diffuse in LV; indeterminate—likely physiological.1813.5
Table 4. Repeat PET scans and changes in immunosuppression during the interval.
Table 4. Repeat PET scans and changes in immunosuppression during the interval.
Case no.Duration Between PETs (Days)HeartExtra-CardiacSUVmax OverallSUVmax SeptumImmunosuppression Change
7211Intense in base of septum and of lateral wall, moderate in remainder of lateral and septal walls, moderate in right ventricle, intense anterior to AP trunk.lungs10.410.3Started rituximab, hydroxychloroquine
Intense in left myocardium, moderate in right myocardium. 9.69.6
8182Moderate diffuse in left ventricle and low-grade in right ventricle; pattern likely physiological.Low-grade axillary nodes and avid subpleural reticulation LLL7.45.5Started steroids, cyclophosphamide, hydroxychloroquine, rituximab
Intense diffuse in left and right myocardium; likely physiological. 19.517.7
12284Moderate in lateral wall and base of anterior and inferior walls, low-grade in base of septum and right ventricle.No7.12.5No change
Intense diffuse in left myocardium and low-grade in right ventricle; likely physiological. 118.2
14258Moderate diffuse in left and right ventricles.Nodes, lungs, spleen6.26.2Started MMF, monthly cyclophosphamide, rituximab, increased steroids
Intense diffuse in left ventricle; likely physiological. 14.614.6
17212Intense diffuse homogeneous in left ventricle.No17.216Started MMF
Same intense diffuse in LV; indeterminate— likely physiological. 1813.5
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Ho, J.S.Y.; Wagner, T.; Denton, C.; Coughlan, J.G.; Knight, D.; Kotecha, T.; Schreiber, B. The Use of 18F-FDG-PET in Systemic Sclerosis with Myocardial Involvement: The Scleroderma Heart Study. Sclerosis 2025, 3, 31. https://doi.org/10.3390/sclerosis3030031

AMA Style

Ho JSY, Wagner T, Denton C, Coughlan JG, Knight D, Kotecha T, Schreiber B. The Use of 18F-FDG-PET in Systemic Sclerosis with Myocardial Involvement: The Scleroderma Heart Study. Sclerosis. 2025; 3(3):31. https://doi.org/10.3390/sclerosis3030031

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Ho, Jamie Sin Ying, Thomas Wagner, Christopher Denton, John Gerry Coughlan, Daniel Knight, Tushar Kotecha, and Benjamin Schreiber. 2025. "The Use of 18F-FDG-PET in Systemic Sclerosis with Myocardial Involvement: The Scleroderma Heart Study" Sclerosis 3, no. 3: 31. https://doi.org/10.3390/sclerosis3030031

APA Style

Ho, J. S. Y., Wagner, T., Denton, C., Coughlan, J. G., Knight, D., Kotecha, T., & Schreiber, B. (2025). The Use of 18F-FDG-PET in Systemic Sclerosis with Myocardial Involvement: The Scleroderma Heart Study. Sclerosis, 3(3), 31. https://doi.org/10.3390/sclerosis3030031

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