The role of serial FDG PET for assessing therapeutic response in patients with cardiac sarcoidosis

doi:10.1007/s12350-016-0682-1

Journal of Nuclear Cardiology

Volume 24, Issue 1, February 2017, Pages 19-28

https://doi.org/10.1007/s12350-016-0682-1 Get rights and content

Abstract

Background

The purpose of this study was to determine the feasibility of serial quantitative 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) to monitor the response of cardiac sarcoidosis to treatment.

Methods and Results

A total of 38 PET scan intervals (54 PET scans) were obtained in 16 patients with cardiac sarcoidosis who underwent serial FDG PET during treatment. FDG-avid lesions of the heart were interpreted quantitatively using 4 PET parameters: maximum standardized uptake value (SUVmax), partial volume corrected mean standardized uptake value (SUVmean), partial volume corrected metabolic volume product (MVP), and global metabolic volume product (gMVP). Clinical response to treatment (improved, stable, or progressive disease) was evaluated by clinical symptoms, NYHA class, and EKG in all the patients. SUVmax, SUVmean, MVP, and gMVP had significantly decreased value on repeat PET in patients who were either stable or showed clinical improvement between two serial PET scans, while none of them had significant change on repeat PET in patients who were clinically worse. Correlation analysis between PET findings and clinical assessment revealed that the changes of SUVmax and SUVmean on repeat PET were negatively correlated with patient’s clinical outcome.

Conclusion

Our results indicated that serial FDG PET is feasible to determine the extent of disease activity and to quantitatively assess the response of cardiac sarcoidosis to therapy.

Spanish Abstract

Antecedentes

El propósito de este estudio fue determinar la factibilidad del estudio PET con FDG cuantitativo realizado en forma seriada para monitorear la respuesta de la sarcoidosis cardiaca al tratamiento.

Métodos y resultados

Se obtuvieron estudios PET en un total de 38 intervalos (54 estudios PET) en 16 pacientes con sarcoidosis cardiaca quienes fueron sometidos al estudio de PET FDG seriado durante su tratamiento. Las lesiones cardiacas ávidas de FDG fueron interpretadas cuantitativamente utilizando 4 parámetros de PET: el valor de captación máximo estandarizado (SUVmax por sus siglas en ingles), valor de captación promedio estandarizado corregido por volumen parcial (SUVmean por sus siglas en ingles), el producto volumen metabólico corregido por el volumen parcial (MVP por sus siglas en ingles) y el producto volumen metabólico global (gMVP por sus siglas en ingles). La respuesta clínica al tratamiento (mejoría, estable o progresión de la enfermedad) fue evaluada en base a los síntomas, la clase funcional de acuerdo a la clasificación de NYHA y ECG en todos los pacientes. Todas las variables cuantitativas SUVmax, SUVmean, MVP y gMVP habían disminuido su valor de forma significativa en el estudio PET de repetición en los pacientes estables o con mejoría clínica entre los dos estudios de PET seriados, mientras que ninguna de ellas tuvo un cambio significativo en el PET de repetición en los pacientes que cursaron con deterioro clínico. El análisis de correlación entre los resultados del PET y la evaluación clínica, reveló que los cambios en los valores SUVmáx y SUVmean en el PET de repetición se correlacionaron de forma negativa con el resultado clínico del paciente.

Conclusión

Nuestros resultados indican el estudio PET con FDG seriado es factible para determinar el grado de actividad de la enfermedad y para evaluar cuantitativamente la respuesta de sarcoidosis cardiaca al tratamiento.

Chinese Abstract

背景

本研究目的是探討FDG PET 连续定量分析應用在評估心脏结节病治疗效果的可行性。

方法和结果

共16 名患有心脏结节病并在治疗过程中以FDG PET扫描作為治療監測的病人。這16位病人接收了54次PET 扫描, 38 个PET 扫描间隔。心脏病灶的FDG PET 显像利用以下参数定量:最大标准摄取值 (SUVmax), 部分体积纠正的平均标准摄取值(SUVmean), 部分体积纠正的代谢体积产物 (MVP), 和整体代谢体积产物(gMVP) 。所有病人的治療效果均以临床症状, NYHA 级别, 及EKG 来评估, 分別為好转、稳定或恶化。对比两次连续的PET 扫描,對于好转和稳定的病人, 其SUV-max, SUVmean, MVP, 和gMVP 都有明显的降低; 然而,对于恶化的病人,这四个指标都没有改变。相关性分析显示SUVmax 和SUVmean 的改变与病人的临床治療反应呈负相关。

结论

FDG PET 连续定量分析可以用来定量评估心脏结节病的活动性以及治疗反应。

Introduction

Sarcoidosis is a systemic disease characterized by non-necrotizing granulomatous inflammation with varying degrees of concomitant fibrosis. It predominantly affects the lung and lymph nodes, but may also involve the heart, liver, spleen, skin, bones, eyes, brain, and other organs.¹ Most patients with sarcoidosis have a favorable outcome, with overall mortality of less than 5%. However, cardiac involvement adversely affects this prognosis due to complications such as conduction abnormalities, ventricular tachycardia, and congestive heart failure. The presence of impaired left ventricular function, poor New York Heart Association (NYHA) functional class, and sustained ventricular tachycardia are also associated with poor survival rate.²

At present, corticosteroids are the first-line agents in the treatment of cardiac sarcoidosis (CS).³^,⁴ Additional treatments including immunosuppressive drugs and heart transplantation are required for those who are not responsive or with progressive disease.⁵ In order to determine the effects of these treatments and to optimize patient care, it is crucial to have reliable parameters that accurately reflect the degree of sarcoidosis activity in the myocardium before and after treatment. However, current parameters such as clinical symptoms, echocardiography, electrocardiogram (ECG), and conventional nuclear medicine scintigraphy have their own limitations. Recently, cardiac magnetic resonance imaging (CMR) has gained importance in the diagnosis of cardiac sarcoidosis. However, CMR may not be feasible in patients with pacemaker or implantable cardioverter defibrillator (ICD) placement.

F-18 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) is a well-established imaging modality for assessing various inflammatory and infectious etiologies, including sarcoidosis.⁶ Recent studies have shown that FDG PET has a high diagnostic accuracy in detecting active myocardial sarcoidosis.7, 8, 9, 10, 11, 12 A recent meta-analysis revealed that FDG PET had a pooled sensitivity of 89% and a pooled specificity of 78% (from 164 patients from six studies) in detecting cardiac sarcoid.¹³ A few studies⁷,13, 14, 15 have revealed that cardiac FDG PET is a useful indicator of cardiac sarcoidosis disease activity. In this study, we correlated clinical findings in CS patients with changes of FDG uptake in cardiac sarcoid lesions in serial FDG PET scans and provided evidence that FDG avidity in serial FDG PET is a useful indicator of disease activity and clinical response to therapy in CS patients.

Section snippets

Subjects

This study was approved by the Institutional Review Board (IRB) of the Hospital of the University of Pennsylvania. We searched our patients’ database retrospectively and identified 70 patients who underwent FDG PET scan for assessment of CS between January 2002 and October 2012. Diagnosis of cardiac sarcoidosis in these patients was established by histopathology or based on the diagnostic standards according to the Japanese Ministry of Health and Welfare guidelines (JMHWG).⁹ Only the patients

Results

The clinical characteristics of patients are summarized in Table 1. A total of 16 patients (9 males and 7 females) met our criteria and were included in this study. The mean age was 48.1 years (range 36-59 years). Four patients had 2 serial PET scans, 5 patients had 3 serial scans, 5 patients had 4 serial scans, one patient had 5 serial scans, and one patient had 6 serial scans. As a result, there were 38 study intervals and 54 PET scans. The average time interval between two serial PET scans

Discussion

FDG PET is a valuable imaging modality in the assessment of cardiac sarcoidosis.19, 20, 21 Patient preparation with high-fat/high-protein and low-carbohydrate diet is critical for this application. FDG uptake in the myocardium is heterogeneous in normal subjects, varying from study to study even in the same person, thus making it impossible to distinguish physiological lesion from pathological one.22, 23, 24 For optimal imaging of CS, minimization of glucose uptake by normal myocardial cells is

Conclusions

This study showed that serial FDG PET is a useful imaging modality for both identifying and monitoring disease activity in cardiac sarcoidosis patients during treatment. Quantitative changes in FDG uptake had a good agreement with disease activity and clinical response to therapy, which, as a result, may help guide titration of immunosuppressive therapy in CS.

New Knowledge Gained

Quantification of FDG uptake in patients with cardiac sarcoidosis can serve as a useful indicator of disease activity and response to therapy.

Disclosure

The authors declared that they have nothing to disclose.

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Cited by (46)

Role of serial <sup>18</sup>F-fludeoxyglucose positron emission tomography in determining the therapeutic efficacy of immunosuppression and clinical outcome in patients with cardiac sarcoidosis
2024, Journal of Nuclear Cardiology
Myocardial inflammation and perfusion defects detected by ¹⁸F-fludeoxyglucose (FDG) and Rubidium-82 positron emission tomography (PET) may be associated with ventricular arrhythmias (VAs) in cardiac sarcoidosis (CS). The role of serial quantitative PET in determining the effect of treatment on myocardial inflammation and clinical outcomes is yet to be defined.
Newly diagnosed CS patients with active myocardial inflammation (maximum standardised uptake value (SUVmax) ≥ 2.5) were treated with immunosuppression, then underwent repeat FDG-PET, Rubidium-82, and echocardiographic imaging 6–12 months later. Serial changes in SUVmax, SUVmean, inflammatory extent, perfusion defect (PD) extent, metabolism/perfusion mismatch extent, global cardiac metabolic activity, and left ventricular ejection fraction (LVEF) were assessed. The primary endpoint was a composite of all-cause mortality, serious VA and heart-failure (HF) hospitalisation. Event data were recorded from the date of the second FDG-PET.
The study population consisted of 113 patients (66% male, age: 55 ± 11 years, LVEF: 54 ± 13%). SUVmax reduced from 4.5 (interquartile range: 3.3–7.1) to 2.7 (2.2–3.6). Overall, 94 (83%) patients saw serial reduction in SUVmax, with 42 (37%) demonstrating complete response (SUVmax <2.5).
Following a median of 46 (25–57) months, 28 (25%) patients reached the endpoint (8 deaths, 17 VAs, and 3 HF hospitalisations). PD extent (Hazard ratio 1.03, 95% confidence interval: 1.01–1.05; p = 0.035) was a significant predictor of outcome following treatment, even after accounting for LVEF and change in SUVmean. The risk of adverse events was the greatest in those with a pre-treatment or post-treatment PD extent of >10%.
In our cohort with active CS, following a treatment-induced reduction in myocardial inflammation, PD extent was the main predictor of adverse events.
Prospective Analysis of Immunosuppressive Therapy in Cardiac Sarcoidosis With Fluorodeoxyglucose Myocardial Accumulation: The PRESTIGE Study
2024, JACC: Cardiovascular Imaging
Fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) can noninvasively assess active inflammatory myocardium in patients with cardiac sarcoidosis (CS). Prednisolone (PSL) is the initial drug of choice for active CS; however, its efficacy has not been prospectively evaluated. Moreover, there are no alternative systematic treatment strategies.
The goal of this study was to evaluate the efficacy of methotrexate (MTX) in patients refractory to PSL assessed by using cardiac metabolic activity (CMA) in ¹⁸F-FDG-PET.
A total of 59 patients with active CS were prospectively enrolled. CMA (standardized uptake value × accumulation area) was used as an indicator of active inflammation, and a 6-month regimen of PSL therapy was introduced, followed by a second FDG scan. Poor responders to PSL therapy (CMA reduction rate <70%) and patients with recurrent CS (CMA reduction rate ≥70% after initial PSL therapy but CMA recurred after an additional 6 months of therapy) were randomly assigned to the MTX or repeat PSL (re-PSL) therapy groups for another 6 months.
Fifty-six patients completed the initial 6-month PSL therapy regimen. Median CMA reduced from 203.3 to 1.0 (P < 0.001), and 47 patients were allocated to the response group, 9 to the poor response group, and 2 to the recurrent group. Accordingly, 11 patients were randomly assigned to the MTX (n = 5) or re-PSL (n = 6) groups. After 6 months, neither group showed a significant reduction in CMA values. MTX was comparable to re-PSL in reducing CMA.
The 6-month regimen of PSL was a potent therapeutic tool for active CS. When MTX was added to low-dose PSL in patients refractory to the initial PSL therapy, there was no significant difference compared with re-PSL. Further studies are needed to evaluate the therapeutic potential of MTX for active CS, including how MTX works when it is administered in higher doses or for longer periods.
Use of PET/CT to detect myocardial inflammation and the risk of malignant arrhythmia in chronic Chagas disease
2023, Journal of Nuclear Cardiology
Chagas heart disease (CHD) is characterized by progressive myocardial inflammation associated with myocardial fibrosis and segmental abnormalities that may lead to malignant ventricular arrhythmia and sudden cardiac death. This arrhythmia might be related to the persistence of parasitemia or inflammation in the myocardium in late-stage CHD. Positron emission tomography/computed tomography (PET/CT) has been used to detect myocardial inflammation in non-ischemic cardiomyopathies, such as sarcoidosis, and might be useful for risk prediction in patients with CHD.
Twenty-four outpatients with chronic CHD were enrolled in this prospective cross-sectional study between May 2019 and March 2022. The patients were divided into two groups: those with sustained ventricular tachycardia and/or aborted sudden cardiac death who required implantable cardioverter-defibrillators, and those with the same stages of CHD and no complex ventricular arrhythmia. Patients underwent ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and ⁶⁸Ga-DOTATOC PET/CT, and blood samples were collected for qualitative parasite assessment by polymerase chain reaction. Although similar proportions of patients with and without complex ventricular arrhythmia showed ¹⁸F-FDG and ⁶⁸Ga-DOTATOC uptake, ⁶⁸Ga-DOTATOC corrected SUV_max was higher in patients with complex arrhythmia (3.4 vs 1.7; P = .046), suggesting that inflammation could be associated with the presence of malignant arrhythmia in the late stages of CHD. We also detected Trypanosoma cruzi in both groups, with a nonsignificant trend of increased parasitemia in the group with malignant arrhythmia (66.7% vs 33.3%).
¹⁸F-FDG and ⁶⁸Ga-DOTATOC uptake on PET/CT may be useful for the detection of myocardial inflammation in patients with Chagas cardiomyopathy, and ⁶⁸Ga-DOTATOC uptake may be associated with the presence of malignant arrhythmia, with potential therapeutic implications.
Prednisone vs methotrexate in treatment naïve cardiac sarcoidosis
2023, Journal of Nuclear Cardiology
Side effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the supporting evidence is poor. This study compared prednisone monotherapy, methotrexate monotherapy or a combination of both, in the reduction of myocardial Fluorine-18 fluorodeoxyglucose (FDG) uptake and clinical stabilization of CS patients.
In this retrospective cohort study, 61 newly diagnosed and treatment naïve CS patients commenced treatment with prednisone (N = 21), methotrexate (N = 30) or prednisone and methotrexate (N = 10) between January 2010 and December 2017. Primary outcome was metabolic response on FDG PET/CT and secondary outcomes were treatment patterns, major adverse cardiovascular events, left ventricular ejection fraction, biomarkers and side effects. At a median treatment duration of 6.2 [5.7-7.2] months, 71.4% of patients were FDG PET/CT responders, and the overall myocardial maximum standardized uptake value decreased from 6.9 [5.0-10.1] to 3.4 [2.1-4.7] (P < 0.001), with no significant differences between treatment groups. During 24 months of follow-up, 7 patients (33.3%; prednisone), 6 patients (20.0%; methotrexate) and 1 patient (10.0%; combination group) experienced at least one major adverse cardiovascular event (P = 0.292). Left ventricular ejection fraction was preserved in all treatment groups.
Significant suppression of cardiac FDG uptake occurred in CS patients after 6 months of prednisone, methotrexate or combination therapy. There were no significant differences in clinical outcomes during follow-up. These results warrant further investigation of methotrexate treatment in CS patients.
The Management of Sarcoidosis in the 2020s by the Primary Care Physician
2023, American Journal of Medicine
Sarcoidosis is an idiopathic granulomatous disease that occurs worldwide and can affect any organ. Because the presenting symptoms of sarcoidosis are not specific for the disease, the primary care physician is usually the first provider to assess these patients. In addition, patients who have previously been diagnosed with sarcoidosis are usually followed longitudinally by primary care physicians. Therefore, these physicians are often the first to address sarcoidosis patient symptoms related to exacerbations of the disease, and first observe complications of sarcoidosis medications. This article outlines the approach to the evaluation, treatment, and monitoring of sarcoidosis patients by the primary care physician.
Hot spot imaging in cardiovascular diseases: an information statement from SNMMI, ASNC, and EANM
2023, Journal of Nuclear Cardiology
This information statement from the Society of Nuclear Medicine and Molecular Imaging, American Society of Nuclear Cardiology, and European Association of Nuclear Medicine describes the performance, interpretation, and reporting of hot spot imaging in nuclear cardiology. The field of nuclear cardiology has historically focused on cold spot imaging for the interpretation of myocardial ischemia and infarction. Hot spot imaging has been an important part of nuclear medicine, particularly for oncology or infection indications, and the use of hot spot imaging in nuclear cardiology continues to expand. This document focuses on image acquisition and processing, methods of quantification, indications, protocols, and reporting of hot spot imaging. Indications discussed include myocardial viability, myocardial inflammation, device or valve infection, large vessel vasculitis, valve calcification and vulnerable plaques, and cardiac amyloidosis. This document contextualizes the foundations of image quantification and highlights reporting in each indication for the cardiac nuclear imager.

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See related editorial, doi:10.1007/s12350-016-0721-y.

JNC thanks Erick Alexanderson MD, Carlos Guitar MD, and Diego Vences MD, UNAM, Mexico for their work in providing the Spanish abstract.

JNC thanks Haipeng Tang, MS, School of Computing, University of Southern Mississippi; Zhixin Jiang, MD, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; and Weihua Zhou, PhD, School of Computing, University of Southern Mississippi, for providing the Chinese abstract.

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Original ArticleThe role of serial FDG PET for assessing therapeutic response in patients with cardiac sarcoidosis

Abstract

Background

Methods and Results

Conclusion

Spanish Abstract

Antecedentes

Métodos y resultados

Conclusión

Chinese Abstract

背景

方法和结果

结论

Introduction

Section snippets

Subjects

Results

Discussion

Conclusions

New Knowledge Gained

Disclosure

Am J Cardiol

Am J Cardiol

Am Heart J

Acad Radiol

J Nucl Cardiol

JACC Cardiovasc Imaging

J Nucl Cardiol

J Am Coll Cardiol

J Nucl Cardiol

J Nucl Cardiol

Imaging features of sarcoidosis on MDCT, FDG PET, and PET/CT

Am J Roentgenol

Corticosteroid treatment in sarcoidosis

Eur Respir J

Identification of cardiac sarcoidosis with (13)N-NH(3)/(18)F-FDG PET

J Nucl Med

Usefulness of fasting 18F-FDG PET in identification of cardiac sarcoidosis

J Nucl Med

Focal uptake on 18F-fluoro-2-deoxyglucose positron emission tomography images indicates cardiac involvement of sarcoidosis

Eur Heart J

Myocardial imaging with 18F-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis

Eur J Nucl Med Mol Imaging

Original Article
The role of serial FDG PET for assessing therapeutic response in patients with cardiac sarcoidosis