The following article is from the Advanced Heart Failure referring provider newsletter.
Cardiac sarcoidosis (CS) is uncommon, difficult to diagnose and even harder to detect after heart transplantation. Veli Topkara, MD, medical director of the Heart Failure, Cardiac Transplantation and Mechanical Circulatory Support Program at UW Health, led a team that recently published an important case study regarding this topic.
In the case study, Dr. Topkara and his colleagues wrote about a 64-year-old heart transplant recipient whose unexplained graft dysfunction ultimately turned out to be recurrent cardiac sarcoidosis, recognized after revisiting pathology from her explanted native heart.
“It’s an important case because it highlights how CS can recur in the transplanted heart,” said Dr. Topkara. “As a result, it may impact post-transplant outcomes.”
A mysterious problem
Six years ago, the patient, who suffered from unexplained cardiomyopathy, underwent a heart transplant at UW Health. It is standard practice for a pathologist to thoroughly examine the explanted heart for signs of, among other conditions, CS. As the pathologist’s report did not raise any red flags, the patient’s doctors proceeded with the usual protocol of post-transplant immunosuppressive medications.
However, in 2025, the patient reported she was experiencing shortness of breath and a reduction in heart capacity. Imaging revealed a significant drop in left ventricular ejection fraction (from 55% down to 29%), with new regional wall motion abnormalities. The patient also had elevated donor specific antibodies. That immediately raised her doctors’ concerns for rejection, transplant coronary artery disease or another inflammatory process affecting the transplanted heart.
The team initially treated the patient for antibody-mediated rejection by giving her high dose steroids, plasmapheresis, bortezomib and intravenous immunoglobulin (IVIG). But while her donor-specific antibody levels declined, her cardiac function did not improve.
“That discordance was a clue,” Dr. Topkara said. “When the heart doesn’t respond as expected to rejection therapy, it’s critical to reassess the diagnosis.”
Team members found another piece of evidence when they received the patient’s endomyocardial biopsy results: There were signs of sarcoidosis in the transplanted heart. Because of this, pathologist Jefree Schulte, MD, returned to the explanted native heart sections, which had been preserved in the pathology lab. He found classical features of cardiac sarcoidosis — non-necrotizing granulomas and giant cells — that had not been emphasized at the time of transplant. That discovery reframed the entire case, explaining her original cardiomyopathy and strongly suggesting recurrence of sarcoidosis in the transplanted heart.
The team followed this up with a cardiac MRI and FDG-PET.
“The MRI showed patchy and transmural late gadolinium enhancement in a nonischemic pattern,” said Dr. Topkara, “and FDG-PET revealed intense, diffuse myocardial uptake. Together, these findings strongly supported active cardiac sarcoidosis and helped us distinguish it from rejection or ischemic disease.”
A change in treatment protocol
After Dr. Topkara and his colleagues arrived at the CS diagnosis, the patient’s treatment plan changed considerably. She was transitioned to methotrexate therapy and high dose steroids for treatment of recurrent CS in the cardiac allograft.
“In this case,” said Dr. Topkara, “methotrexate led to clear clinical improvement, recovery of left ventricular function and dramatic reduction in FDG uptake on serial PET scans. This supports emerging evidence that methotrexate can be particularly effective for cardiac sarcoidosis, including in transplant recipients.”
“After we started the combination treatment of methotrexate and high dose steroids,” Dr. Topkara continued, “within six months, we were able to clear the inflammation from her heart.”
“If acute cellular rejection, antibody-mediated rejection and cardiac allograft vasculopathy don’t fully explain the clinical picture,” Dr. Topkara added, “clinicians should have a low threshold to consider recurrent cardiac sarcoidosis — especially in middle-aged women with prior nonischemic cardiomyopathy. It is often essential to have multidisciplinary collaboration between cardiology, pathology, radiology and rheumatology to achieve best outcomes.”
Conclusion
The most important lesson learned during treatment of this patient, Dr. Topkara said, is that cardiac sarcoidosis does not end with transplantation. When it is overlooked, it can quietly return, masquerading as rejection. Only a high index of suspicion, careful pathology review and advanced imaging can reveal the true diagnosis.
And if CS is confirmed in a patient, it must be aggressively treated. “For patients with known CS going into transplant, they probably should stay on lifelong treatment,” he said.
Finally, thorough examination of the explanted heart is essential.
“The explanted heart must always be examined top to bottom by the pathologist,” Dr. Topkara said. “If you miss it and wean the steroids after transplant, the sarcoid may come back.”
Cole M., et al. Recurrent Cardiac Sarcoidosis After Heart Transplantation. Journal of the American College of Cardiology.