Original Article
Prognosis and recurrence in cardiac sarcoidosis: Serial assessment of BMIPP SPECT and FDG-PET

https://doi.org/10.1007/s12350-021-02567-0Get rights and content

Abstract

Background

We analyzed 18F-Fludeoxyglucose positron emission tomography (FDG-PET) and 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) performed for cardiac sarcoidosis (CS) patients taking prednisolone, identified recurrence by FDG-PET, and investigated BMIPP as a recurrence and prognostic factor in CS.

Methods and Results

CS patients who underwent BMIPP and FDG-PET within 2 months were enrolled. The recurrence-free group included patients with standardized uptake value (SUVmax) < 4 in the myocardium consecutively for ≥ 2 years. The total BMIPP SPECT defect score (BDS) was used to estimate myocardial damage. The predictability of the initial BDS and SUVmax for major adverse cardiac events (MACE) was analyzed using Kaplan–Meier analysis. Overall, 73 patients and 250 BMIPP and FDG-PET sets were analyzed retrospectively (mean follow-up, 3.5 years). The BDS was significantly greater for the recurrence group (N = 21) vs recurrence-free group (20 ± 13 vs 14 ± 12, P = 0.041). Patients with BDS ≥16 had a significantly higher MACE rate than patients with BDS < 16 (log-rank test, P = 0.016). However, MACE occurrence was comparable between patients with SUVmax ≥ 4 and < 4.

Conclusions

BDS is a predictive marker of recurrence and MACE. SUV is not related to MACE. Recurrence, defined by prednisolone treatment-induced SUV variability, was observed in approximately 30% of CS patients.

Introduction

Sarcoidosis is a systemic chronic inflammatory disease of unknown etiology characterized by the presence of noncaseating granulomas that can affect various organs. Cardiac involvement in sarcoidosis is associated with conduction disturbance, ventricular tachycardia, congestive heart failure, and sudden cardiac death, and it is one of the major causes of disease-related death.1 Steroid therapy is the mainstay of treating cardiac sarcoidosis (CS), with general efficacy of approximately 50%.2 Corticosteroid-refractory CS patients require a change in therapeutic strategy and may consider additional immunosuppressants or implantation of cardiac defibrillators. However, the prognosis for these patients is poor.

Noninvasive cardiac imaging has recently been developed. 18F-Fludeoxyglucose positron emission tomography (FDG-PET) and cardiac magnetic resonance (CMR) late gadolinium enhancement were added to the Japanese Ministry of Health and Welfare modified diagnostic criteria for CS in 2017.1,3, 4, 5, 6, 7 Studies reported that long-term fasting FDG-PET for the inhibition of physiological uptake has contributed to the diagnosis and detection of active inflammation in CS.3,8 Moreover, monitoring the standardized uptake value (SUV) obtained from FDG-PET during steroid therapy has been reported to be useful in predicting treatment response.9

123I-betamethyl-p-iodophenyl-pentadecanoic acid single-photon emission computed tomography (BMIPP SPECT) was developed to evaluate fatty acid metabolism and is now widely used in Japan to detect myocardial ischemia without stress testing in unstable or vasospastic angina.10,11 This is based on the phenomenon of ischemic memory in which fatty acid metabolism is more impaired than perfusion injury due to ischemia. Additionally, Momose et al. reported that BMIPP was effective in detecting myocardial damage in CS.12

This study aimed to investigate the relationship between recurrence and myocardial damage obtained from BMIPP SPECT, and to explore the potential of BMIPP and FDG-PET as prognostic factors in CS patients undergoing steroid therapy.

Section snippets

Study Population

This study was a single-center, retrospective study of 73 consecutive patients diagnosed with cardiac sarcoidosis between January 2010 and May 2018 based on the Guidelines for Diagnosis and Treatment of Cardiac Sarcoidosis by the Japanese Circulation Society.13,14 Patients who were diagnosed with cardiac sarcoidosis in the past or who were taking prednisolone for other diseases were excluded. All patients underwent invasive coronary artery angiography and had no obstructive coronary artery

Patient Characteristics

Seventy-three patients (mean age, 61 years; male, 38%) and 250 datasets of BMIPP or FDG-PET (mean interval, 14 days; range 1 to 60 days) were analyzed retrospectively. Endomyocardial biopsy was performed in 68 out of 73 patients (93%). For the remaining five patients (7%), biopsy was not performed because of the high risk of complications associated with their advanced age or a coexisting complete left bundle branch block. For 24 patients (33%) with isolated cardiac sarcoidosis, biopsies were

Discussion

The present study demonstrates that BDS obtained from BMIPP at initial assessment was significantly greater in the recurrence group than in the recurrence-free group. Furthermore, to our knowledge, the present study is the first to demonstrate that BDS is a valid indicator for predicting MACE in CS patients. We propose a new definition for the recurrence of CS under steroid therapy using the change in SUV obtained from serial FDG-PET studies. The recurrence rate was approximately 30% and was

Conclusion

BDS obtained from BMIPP is a predictive marker of recurrence and MACE, whereas SUV is not related to the MACE rate. Recurrence, defined by prednisolone treatment-induced SUV variability, was observed in approximately 30% of CS patients. BDS may aid in determining appropriate FDG-PET protocols and treatment strategies.

New Knowledge Gained

This study proposed that recurrence was defined by serial FDG-PET assessment and demonstrated that the rate of recurrence was approximately 30% in patients with CS. Moreover, BDS was a valid predictor of recurrence and MACE and can help determine appropriate FDG-PET protocols and treatment strategies for the first time.

Disclosures

Atsushi Yamamoto, Michinobu Nagao, Eri Watanabe, Yasutaka Imamura, Atsushi Suzuki, Kenji Fukushima, Kiyoe Ando, Risako Nakao, Akiko Sakai, Mitsuru Momose, Shuji Sakai, Nobuhisa Hagiwara have no conflicts of interest to declare.

References (25)

  • PatelMR et al.

    Detection of myocardial damage in patients with sarcoidosis

    Circulation

    (2009)
  • MaruokaY et al.

    Evaluation of response to steroid therapy for cardiac sarcoidosis using volumetric analysis of 18F-FDG PET/CT

    J Bioanal Biomed

    (2015)

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