Cardiovascular Magnetic Resonance Imaging Phenotypes and Long-term Outcomes in Patients With Suspected Cardiac Sarcoidosis

Abstract

ImportanceIn patients with sarcoidosis with suspected cardiac involvement, late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging (CMR) identifies those with an increased risk of adverse outcomes. However, these outcomes are experienced by only a minority of patients with LGE, and identifying this subgroup may improve treatment and outcomes in these patients.ObjectiveTo assess whether CMR phenotypes based on left ventricular ejection fraction (LVEF) and LGE in patients with suspected cardiac sarcoidosis (CS) are associated with adverse outcomes during follow-up.Design, Setting, and ParticipantsThis cohort study included consecutive patients with histologically proven sarcoidosis who underwent CMR for the evaluation of suspected CS from 2004 to 2020 with a median follow-up of 4.3 years at an academic medical center in Minnesota. Demographic data, medical history, comorbidities, medications, and outcome data were collected blinded to CMR data.ExposuresCMR phenotypes were identified based on LVEF and LGE presence and features. LGE was classified as pathology-frequent or pathology-rare based on the frequency of cardiac damage features on gross pathology assessment of the hearts of patients with CS who had sudden cardiac death or cardiac transplant.Main Outcomes and MeasuresComposite of ventricular arrhythmic events and composite of heart failure events.ResultsAmong 504 patients (mean [SD] age, 54.1 [12.5] years; 242 [48.0%] female and 262 [52.0%] male; 2 [0.4%] American Indian or Alaska Native, 6 [1.2%] Asian, 90 [17.9%] Black or African American, 399 [79.2%] White, 5 [1.0%] of 2 or more races (including the above-mentioned categories and Native Hawaiian or Other Pacific Islander), and 2 [0.4%] of unknown race; 4 [0.8%] Hispanic or Latino, 498 [98.8%] not Hispanic or Latino, and 2 [0.4%] of unknown ethnicity), 4 distinct CMR phenotypes were identified: normal LVEF and no LGE (n = 290; 57.5%), abnormal LVEF and no LGE (n = 53; 10.5%), pathology-frequent LGE (n = 103; 20.4%), and pathology-rare LGE (n = 58; 11.5%). The phenotype with pathology-frequent LGE was associated with a high risk of arrhythmic events (hazard ratio [HR], 12.12; 95% CI, 3.62-40.57; P < .001) independent of LVEF and extent of left ventricular late gadolinium enhancement (LVLGE). It was also associated with a high risk of heart failure events (HR, 2.49; 95% CI, 1.19-5.22; P = .02) independent of age, pulmonary hypertension, LVEF, right ventricular ejection fraction, and LVLGE extent. Risk of arrhythmic events was greater with an increasing number of pathology-frequent LGE features. The absence of the pathology-frequent LGE phenotype was associated with a low risk of arrhythmic events, even in the presence of LGE or abnormal LVEF.Conclusions and RelevanceThis cohort study found that a CMR phenotype involving pathology-frequent LGE features was associated with a high risk of arrhythmic and heart failure events in patients with sarcoidosis. The findings indicate that CMR phenotypes could be used to optimize clinical decision-making for treatment options, such as implantable cardioverter-defibrillators.

An Elderly Woman With Ventricular Tachycardia

“…Second, determining individual patient prognosis and assessment of immunosuppression response in patients with CS using cardiac imaging remains challenging. It has been demonstrated that patients without LGE are at an extremely low risk of arrhythmic events . However, although there is increased risk of arrhythmic events in patients with cardiac involvement identified by LGE, only a fraction of these patients experience arrhythmic events.…”

“…However, although there is increased risk of arrhythmic events in patients with cardiac involvement identified by LGE, only a fraction of these patients experience arrhythmic events. Patients with both RV and LV LGE are at elevated risk of cardiovascular events compared with patients with only LV enhancement . Last, while CS is extremely rare after 70 years of age, as the oldest patient reported in the literature was 80 years old, this patient presented with CS in her 90s, reminding us that CS remains on the differential diagnosis in patients with sustained ventricular arrythmias regardless of age.…”

Diagnostic testing in cardiac sarcoidosis: what comes first?

“…Recent CMR data identifying the LGE phenotypes associated with arrhythmic outcomes may help. [10][11][12] Athwal et al demonstrated that LGE phenotypes of CS derived from the pathology and validated by clinical outcomes are associated with worse outcomes but absence of the pathology frequent LGE phenotype was associated with a low risk of arrhythmic events, even in the presence of other (pathology rare)…”

“…Thus, association of any LGE to the clinical outcomes is CS patients may not be strong. 10 Even though edema imaging on CMR has low sensitivity to detect myocardial inflammation compared with FDG-PET, 13 there are no studies of PET positive, LGE negative histology proven CS. In CMR studies, patients with clinically suspected CS and no LGE have extremely low likelihood of developing ventricular arrythmias sudden cardiac death or heart failure.…”

“…In CMR studies, patients with clinically suspected CS and no LGE have extremely low likelihood of developing ventricular arrythmias sudden cardiac death or heart failure. 10 For the patients that have high risk pathology frequent LGE may benefit from FDG-PET for further confirmation of active inflammation to evaluate eligibility for CS treatment. FDG uptake remains highly dependent on patient preparation and myocardial metabolism, isolated use of FDG-PET in CS diagnostic algorithm remains clinically limited.…”