Managing Cardiac Sarcoidosis: Complexities of the Heart

Sarcoidosis is a disease that affects the immune system, causing inflammation and the formation of granulomas, or small clumps of immune cells, in various organs of the body. While the disease predominantly affects the lungs, it’s also found in the skin, eyes, and in some cases, the heart.

The condition affects more than 1 million individuals globally, with an estimated prevalence range of 150-200 thousand in the US.1 The impact on Black or African American patients is disproportionate, with 3 times the incidence compared to White patients.

Beyond that, African American women are more likely to be affected by the disease than African American men by an additional 50%, Ogugua Obi, MD, MPH, MSc, director of the Sarcoidosis Center of Excellence at East Carolina University (ECU) told HCPLive.

Management of sarcoidosis is impacted by multifaceted barriers, ranging from limited treatment options and access to racial and socioeconomic factors, all of which are significantly more pronounced for African American women.

Of the various forms, cardiac sarcoidosis is reportedly the rarest, occurring in 10-15% of cases. However, in recent years, cardiologists have seen more cases of sarcoidosis in the heart, which often results in severe outcomes, Matthew Lander, MD from the Division of Advanced Heart Failure and Transplantation Cardiology, Cardiovascular Institute, Allegheny Health Network (AHN), told HCPLive.

"The reason (cardiac sarcoidosis) is so important is a larger proportion of patients with sarcoid have a cardiac morbidity, or even mortality later on, suggesting that, while the cardiac involvement historically has been felt to be only in the 10, 15, maybe 20% range, I think there's a lot of us that think that's because we just haven't found it,” Lander said.

Therapies: Small But Growing

At this time, prednisone and repository-corticotropin injection (Acthar gel) are the only therapies approved by the US Food and Drug Administration (FDA) for the treatment of sarcoidosis; however, there is no treatment indicated for cases that involve the heart.

Corticosteroid therapy is typically the first implemented in patients with sarcoidosis but because the disease is characterized by a wide range of variability, discerning which intervention is best can be complicated.

It's crucial to understand how the disease is presenting in a patient because corticosteroid treatment has effects that shouldn't be taken lightly, Lander explained. Prescribing corticosteroids or methotrexate can be done by almost any practitioner, but unless the entirety of the patient's disease is understood, he recommends connecting with a specialist.

When present in the heart, treating sarcoidosis has implications of risk.

"Sometimes people get put on prednisone, somewhat unnecessarily—even just for a week or 2— and that can be very significant for them, prednisone can lead to increased hunger drive, increased thirst, drive fluid retention," he said. "So, in a very short period of time, if someone with heart failure is on prednisone, it can lead to heart failure exacerbation, so the volume aspect is probably the biggest issue."

Several medications that can be effective for heart failure with reduced ejection fraction include standard beta-blockers, mineralocorticoid receptor antagonists like spironolactone, and ACE inhibitors or ARB therapy, with RNA therapy such as Cubetto valsartan being a standard if ACE inhibitors are not tolerated. More recently, the effectiveness of SGLT2 inhibitors such as empagliflozin and dapagliflozin was discovered.

Diagnosis: Much to Learn

Cardiac involvement has a severe impact on the patient “far exceeding its relatively lower incidence in the disease.” Lander stressed the importance of screening patients to determine whether the disease could be affecting the heart.

This condition can be especially difficult to diagnose as the symptoms may be nonspecific–mimicking other heart conditions. Oftentimes, it’s discovered when investigating the cause of certain symptoms.

Specifically, a patient presenting with arrhythmia, heart failure, or other cardiac complications could indicate sarcoid of the heart. Observing the effect on the electrical system can guide diagnosis, as conduction abnormalities, or reduced ejection fraction, are often the first markers that Lander notices.

The best method of screening for cardiac sarcoidosis is still being understood. An echocardiogram (EKG) may provide useful information, according to the Foundation for Sarcoidosis research, but advanced cardiac imaging may be necessary.²

“We find in our patients that have heart failure or reduced ejection fraction, that it certainly can have a specific pattern on imaging, on echocardiogram, on cardiac MRI,” he explained, “and the testing modality that's changing how we view this disease a lot, is PET scanning.

By enacting fluorodeoxyglucose (FDG) as a radiotracer during positron emission tomography (PET) scans, glucose-energized cells can illuminate areas of inflammation.

Results from a recent investigation on the prognostic value of MRI and PET for patients with cardiac sarcoidosis, the ventricles are regions of interest for activity linked with the condition.

Matthew Aitken, Department of Medical Imaging, Toronto General Hospital, University Health Network, University of Toronto, and study investigators acknowledged the fact that both imaging biomarkers were predictive of major adverse cardiac events (MACE), highlighting the importance of both inflammation and fibrosis in the progression of cardiac sarcoidosis.³

Late gadolinium enhancement (LGE) at MRI exhibited a stronger predictor than FDG uptake at PET, possibly reflecting differences in the underlying pathophysiology of the disease.

The study also highlighted the challenges in diagnosing cardiac sarcoidosis and the potential of these imaging biomarkers in aiding diagnosis and guiding clinical decision-making in the management of this challenging disease.

Barriers: Building Trust

Treating sarcoidosis is optimized with a multidisciplinary approach–including different medical specialists to ensure that the patient receives comprehensive care, especially in cardiac cases.

The delicate decision of intervention poses a challenge without any approved treatments and because of the risk associated with first-line approaches. High-dose steroid treatment can worsen heart failure and glycemic control in patients with diabetes, making communication among all the patient's providers imperative to avoid any negative interactions between treatments.

“We want the treatment intensity to fit what we feel like we're trying to achieve,” Lander said. “Once we start the treatment, we don't really want to just dip the toe in.”

Beyond treatment, the impact of the barriers associated with sarcoidosis is backed by research. In the US, more than 50% of a patient's disease outcome is based on their zip code, or socioeconomic status, Obi stated.

Implicit and explicit biases play a significant role in the provider-patient relationship from both sides. In addition to racial barriers, there’s evidence demonstrating that women are treated differently than men by providers, she explained.

"If you don't trust your physician if you don't feel like your physician is listening to you or hearing you," Obi said, "you're less likely to make appointments, you're also less likely to be adherent to the medications or to whatever the treatment plan is."

Conclusion

With cardiac sarcoidosis, both the underlying condition and any associated conditions such as heart failure, arrhythmia, or conduction system disease need to be addressed.

While corticosteroid therapy is typically used in patients with sarcoidosis, with no approved treatment for heart involvement, treatment becomes more complicated. It's crucial to screen patients to determine whether the disease could be affecting the heart and observe the effect on the electrical system can guide diagnosis.

Furthermore, the progress made in cardiac imaging, particularly PET scanning, provided a valuable aid for diagnosis. Although, communication remains a critical tool for clinical decision-making in the management of this challenging disease.

References

1. ^{Foundation for Sarcoidosis Research. What is Sarcoidosis? Accessed March 21, 2023. https://www.stopsarcoidosis.org/what-is-sarcoidosis/}
2. ^{Foundation for Sarcoidosis Research. Sarcoidosis Treatment Guidelines. Accessed March 23, 2023. https://www.stopsarcoidosis.org/wp-content/uploads/Treatment-Protocol.pdf}
3. ^{Aitken, M., Davidson, M., Chan, M. V., Urzua Fresno, C., Vasquez, L. I., Huo, Y. R., McAllister, B. J., Broncano, J., Thavendiranathan, P., McInnes, M. D., Iwanochko, M. R., Balter, M., Moayedi, Y., Farrell, A., & Hanneman, K. (2023). Prognostic value of cardiac MRI and FDG PET in cardiac sarcoidosis: A systematic review and meta-analysis. Radiology. https://doi.org/10.1148/radiol.222483}