Registry study finds heart sarcoidosis outcomes vary by feature

Outcomes among more than 1,800 people newly diagnosed with cardiac sarcoidosis differed by diagnostic features, including heart tissue sampling to confirm the disease and whether it also affected other organs, a large real-world study using registry data found.

The group of patients diagnosed without a heart biopsy and with disease involvement outside the heart showed the poorest outcomes and “needs to be treated separately,” the researchers wrote. A heart biopsy involves collecting a small sample of heart tissue for analysis under a microscope.

The study, “Management and Outcomes of Cardiac Sarcoidosis: Insights From the Nationwide MYSTICS Registry,” was published in Circulation: Heart Failure.

In sarcoidosis, clusters of immune cells, called granulomas, form in various tissues and organs, causing damage and interfering with their function.

Cardiac sarcoidosis refers to granulomas forming in the heart, typically the heart muscle, which disrupt the heart’s electrical system and cause irregular heartbeats (arrhythmias). This can lead to serious outcomes, including heart failure and sudden cardiac death.

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Nonspecific, varying symptoms make diagnosis a challenge

Diagnosis of cardiac sarcoidosis is difficult because most manifestations are nonspecific, leading doctors to consider other causes. In addition to its rarity, cardiac sarcoidosis symptoms may vary widely from person to person, and heart muscle biopsies can miss affected areas. That makes it important to evaluate real-world management and outcomes in a large group of people with cardiac sarcoidosis.

With this in mind, a team of researchers gathered data from the MYSTICS registry, a large observational study of cardiac sarcoidosis patients seen at 115 hospitals across Japan. Their analysis involved 1,852 adults (mean age 63, 65% women) diagnosed with cardiac sarcoidosis from 2012 to 2021.

After enrollment, nearly all participants (89%) received corticosteroids, while some (8.3%) received other immunosuppressive treatments, mostly methotrexate. Electrical devices to monitor and regulate the heart’s rhythm were implanted in one-fourth of patients (24%), while a few received a mechanical pump to help blood flow from the heart or underwent a heart transplant.

The researchers placed patients into four groups based on diagnostic criteria. One group had definite cardiac sarcoidosis (191 patients) and another had probable cardiac sarcoidosis (687 patients), both based on the 2014 Heart Rhythm Society criteria.

A third group had presumed systemic, or whole-body, sarcoidosis (616 patients), while the fourth had presumed isolated cardiac sarcoidosis (358 patients), both without tissue (histological) evidence and based on clinical diagnostic criteria of the 2016 Japanese Circulation Society guidelines.

The researchers analyzed the proportion of patients who, during follow-up, reached a main outcome of death by any cause, hospitalization for heart failure, or fatal ventricular arrhythmic event (a life-threatening arrhythmia originating in the heart’s lower left chamber).

Over a median follow-up of 5.1 years, 28% of the participants reached that composite outcome, 9.5% died, 12% had a heart failure-related hospitalization, and 16% experienced a fatal ventricular arrhythmic event.

Overall, the five-year cumulative frequency of the composite outcome was 27.2%. This frequency was highest in the presumed isolated cardiac sarcoidosis group (42.9%), followed by the definite cardiac sarcoidosis group (33.6%), presumed systemic cardiac sarcoidosis group (23.4%), and probable cardiac sarcoidosis group (20.8%).

The first and fourth groups also had significantly higher rates of fatal ventricular arrhythmic events and heart failure-related hospitalization. Cardiovascular death and all-cause death were significantly more frequent in group four, while non-cardiovascular death was similar across the groups.

Additional analyses showed that several factors were significantly associated with the main outcomes, including older age, male sex, a history of heart failure, and a history of arrhythmias affecting the heart’s lower chambers.

Other contributing factors were a high blood level of BNP (a blood marker of heart strain), a lower amount of blood pumped out of the heart with each beat, and the absence of disease involvement outside the heart.

The researchers then assessed disease recurrence, based on imaging studies, in 1,647 patients who received corticosteroids or other immunosuppressive agents. During follow-up, 291 people (18%) experienced recurrence during corticosteroid tapering, yielding a five-year cumulative rate of 17%. Most patients (82%) increased their corticosteroid dose after recurrence.

The five-year recurrence rate was similar across groups. Recurrence timing, corticosteroid dose at recurrence, and treatment after recurrence diagnosis also did not differ among groups.

Recurrence was significantly associated with a 38% higher risk of subsequently reaching the main outcome. Among the 245 patients who did not experience the main outcome before the recurrence, 39 had symptoms at the time of recurrence, such as worsening heart failure or arrhythmias.

Patients with symptoms at recurrence were significantly more likely to subsequently experience the main outcome than those whose recurrence was detected by imaging alone.

The study “showed that clinical presentations and prognoses differ depending on the presence or absence of … lesions [outside the heart] and histological evidence,” the researchers wrote. “Therefore, it is necessary to recognize the characteristics of each [type] in managing [cardiac sarcoidosis].”

“A large-scale prospective registry is warranted to further clarify clinical outcomes and guide management,” the team added.