Heart block in a 60-year-old man with undiagnosed cardiac sarcoidosis

Discussion

The many causes of pathologic AV block include congenital and acquired forms (Box 1). Degenerative causes are by far the most common and are associated with age-related degeneration and fibrosis of the conduction system, diabetes and hypertension.3 In 1 retrospective analysis, 0.6% of controls and as many as 1.1% of patients in hospital (age 65.8 ± 11.3 yr) with diabetes had complete AV block.4

If patients are clinically stable, common and potentially reversible causes of AV block (which are common in patients younger than 65 years) should be considered and treated before a permanent pacemaker is inserted. Reversible causes include medications, ischemia, hyperkalemia, thyroid dysfunction and infections such as Lyme carditis. Lyme disease is a vector-borne infectious illness with dramatically increasing incidence in parts of Canada (144 cases in 2009; 2025 cases in 2017).5 Atrioventricular block is present in 90% of patients with Lyme carditis and resolves with antibiotics in most cases.5

Sarcoidosis is a multisystem granulomatous disease of unknown cause; its hallmark is noncaseating granulomas on biopsy. It primarily affects people in their third to fourth decade of life.6 Sarcoidosis more commonly affects women, nonsmokers, individuals of African descent and residents in northern latitudes.6 In 1 Ontario cohort study, the prevalence of sarcoidosis increased between 1996 and 2015, from 66 to 143 cases per 100 000;7 increasing prevalence is seen worldwide. Sarcoidosis is a great mimicker of other diseases, making diagnosis challenging.

The lungs and hilar lymph nodes are involved in about 90% of patients with sarcoidosis. However, sarcoidosis can also affect other organs, including the heart, liver, skin and eyes. Cardiac sarcoidosis (CS) can be the first clinical manifestation and is associated with a poorer prognosis owing to heart failure or sudden cardiac death.8 In 1 study, only 19% of patients with EF below 30% were alive after 10 years.9 Cardiac involvement in sarcoidosis has been reported in as many as 27% of autopsy studies in some North American cohorts, but many cases may be undiagnosed.10

Clinical features of CS include conduction abnormalities such as ventricular tachycardia and atrioventricular blocks, heart failure and sudden cardiac death, and nonspecific symptoms like chest pain, fatigue and presyncope.8 The degree, location and extent of inflammation and fibrosis influence the clinical presentation. For instance, a patient with CS localized to the AV node may present acutely with heart block, but a patient with CS in a patchy distribution may be asymptomatic, despite being at higher risk for heart failure and ventricular arrhythmias.

Diagnosis of CS is histologic, from myocardial tissue, or clinical, based on history and results of invasive and noninvasive investigations. 1 Biomarkers, electrocardiograms and TTE are first-line tests that frequently yield nonspecific findings. For instance, TTE may show regional wall motion abnormalities in a noncoronary distribution with or without LV systolic dysfunction, basal interventricular septum thinning and reduced global longitudinal strain. The gold standard remains endomyocardial biopsy; however, the yield from biopsy is less than 50%.11 Electroanatomic mapping shows promise in increasing the yield for endomyocardial biopsy.12 If tissue diagnosis is not feasible, consensus guidelines from the Heart Rhythm Society and the Japanese Ministry of Health and Welfare criteria can be used.8 Hybrid cardiac MRI and fluorodeoxyglucose PET imaging detects both inflammation and scar in CS and thus effectively highlights these separate stages of CS in 1 modality.13 Ideally, this should be completed 3 months after starting or stopping treatment and if there is a change in symptoms.1^,8 Hybrid PET and MRI imaging displays greater sensitivity and specificity in detecting inflammation than PET or MRI alone.14 This is a novel modality for detection of CS, which exposes the patient to less radiation.

Data on screening for CS in patients with a diagnosis of sarcoidosis are limited; however, the findings of 1 study of diagnostic and prognostic investigations in an outpatient setting suggested that if a patient has palpitations, syncope or presyncope, an ECG, Holter and TTE should be completed.15 Abnormal screening tests and ongoing clinical suspicion for CS should trigger further testing with MRI, PET or hybrid imaging.

Management of CS can be challenging and referral to a cardiologist with expertise in CS is recommended.1 Immunosuppression with prednisone is the mainstay of treatment for CS1 and should be considered when there is imaging evidence of myocardial inflammation and either atrioventricular blocks, frequent nonsustained or sustained ventricular tachycardia, or LV dysfunction. 8 In addition to glucocorticoids, steroid-sparing agents such as methotrexate, azathioprine and mycophenolate may be considered. Currently, the Cardiac Sarcoidosis Randomized Trial is ongoing, in which patients with CS are randomized to prednisone or prednisone and methotrexate; the trial will provide useful evidence for the treatment of CS.16 Biologic agents are thirdline therapy and their use has been reported in only a small number of cases. Implantable cardioverter-defibrillator therapy should be considered, as patients with sarcoidosis can be susceptible to ventricular arrhythmias.

For patients younger than 65 years who present with heart block, CS should be considered along with other nonischemic causes. Novel imaging techniques such as hybrid PET and MRI have increased the sensitivity and specificity for diagnosis, and ongoing trials will shed further light on management.