Case Study: Cardiac Sarcoidosis in Man With Palpitations, Dyspnea

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study.

Why has this previously healthy man had increasingly debilitating dyspnea and fatigue over the previous 6 months?

That's the diagnostic challenge that faced Nikita Jhawar, MD, of the Mayo Clinic in Jacksonville, Florida, and colleagues when the patient presented to the emergency department with palpitations and shortness of breath.

As they described in their Challenges in Clinical Electrocardiography case report in JAMA Internal Medicine, when the patient presented for assessment after 6 months of symptoms, the team performed a simultaneously recorded 3-lead rhythm electrocardiogram (ECG), and then administered intravenous amiodarone followed by a 12-lead ECG, and compared findings of the two ECGs.

The first 3-lead rhythm ECG taken on presentation showed salvos of wide QRS complex tachycardia that terminated spontaneously, with several sinus rhythm beats between salvos, the authors noted.

The sixth and 15th QRS complexes were fusion complexes with an intermediate morphology between the sinus conducted QRS complex (fifth and 16th QRS) and the wide QRS complex tachycardia, which Jhawar and co-authors said was most evident in leads V1 and V5.

Given the noted fusion complexes, clinicians considered that the wide QRS complex salvos confirmed a diagnosis of ventricular tachycardia (VT). The team observed "retrograde P waves ... in lead V1 in the ST-T waves after the first to fourth and the eighth to 12th QRS complexes," when compared with the ST-T waves after the seventh QRS complex.

The wide QRS complex tachycardias terminated with retrograde P waves after the fourth and 12th QRS complexes, Jhawar and co-authors said. This confirmed that the patient had ventricular tachycardia with retrograde conduction, "because in atrial tachycardia with aberrant conduction, atrial activity drives ventricular activity and the tachycardia will thus terminate with a QRS complex."

After the patient was treated with intravenous amiodarone, his sinus rhythm rate was 115 bpm on a 12-lead ECG, with low-voltage QRS complexes evident in all leads -- generally defined as all frontal QRS complexes <5 mm and/or precordial QRS complexes <10 mm -- and T wave inversion in the anterior precordial leads and diffuse, nonspecific ST-T waves throughout, the authors explained. In addition, small discrete positive deflections were seen in the precordial leads after the QRS and prior to the onset of the T wave. There were also small discrete positive deflections in the precordial leads after the QRS and before the onset of the T-wave, which was most evident in leads V1-V3.

The team performed an echocardiogram, which showed that the patient had a left ventricular ejection fraction of 32%. Beyond noting a dilated right ventricle with reduced function, there was no evidence of valvular dysfunction, wall motion abnormalities, ventricular hypertrophy, or shunts.

The team used cardiac MRI to confirm the diagnosis, which showed decreased left ventricular function, significant enlargement of the right ventricle, and patchy areas of delayed gadolinium contrast without evidence of fat in both the left and right ventricles.

Subsequently, clinicians performed an endomyocardial biopsy of the right ventricle, which revealed giant cells and no evidence of mixed inflammatory cells or fatty infiltration. These findings were more suggestive of cardiac sarcoidosis than arrhythmogenic cardiomyopathy (ACM). "As such, epsilon waves are not necessarily pathognomonic for ACM and may be seen in cardiac sarcoidosis," Jhawar and colleagues said.

They noted that after being diagnosed with sarcoidosis, the patient had progressive deterioration despite receiving anti-inflammatory therapies, but eventually underwent an orthotopic heart transplant, and since then, has continued to do well.

Discussion

The small deflections seen on the ECG are epsilon waves, the case authors explained. This phenomenon was first reported in the 1970s in a patient who had suffered a heart attack and several episodes of ventricular tachycardia. Later, the epsilon wave was linked with arrhythmogenic right ventricular cardiomyopathy (ARVC) in up to 25% of cases, and accepted as one of the major diagnostic criteria for the condition.

"More recently it has been recognized that ARVC, although more apparent in the right ventricle, can also involve the left ventricle in combination with the right ventricle or in isolation and is referred to as arrhythmogenic cardiomyopathy," Jhawar and co-authors said. This is a genetic disease and has been associated with desmosomal variations (most commonly plakophilin), as well as nondesmosomal genes such as titin.

"In ACM, normal myocardium is replaced by fatty or fibrofatty tissue with small regions of myocardial tissue," the team continued. "The epsilon wave is thought to be a manifestation of delayed ventricular depolarization in these regions relative to normal depolarization occurring in the remainder of the heart."

While epsilon waves are typical signs of ACM, they also occur in the presence of small areas of relatively delayed ventricular depolarization, such as in the setting of infiltrative heart diseases, coronary artery disease, Uhl anomaly, and tetralogy of Fallot.

Cardiac sarcoidosis is a systemic granulomatous disease that seems more common in people in Northern Europe and in Africa, the authors explained, adding that the condition appears to be due to an initial environmental antigen that stimulates an immune response leading to granuloma formation.

The diagnosis is generally considered in patients with idiopathic atrioventricular block, the case authors noted. Rarely, ventricular arrhythmias can also be a presenting symptom of cardiac sarcoidosis, and as such are associated with a 9-34% risk of sudden cardiac death within 5 years.

The team emphasized that while epsilon waves are generally seen in the setting of arrhythmogenic cardiomyopathy, they may also be associated with other disorders, including cardiac sarcoidosis.

Read previous installments in this series:

Part 1: Cardiomyopathy: What are the Signs, What are the Symptoms?

Part 2: Diagnosing Cardiomyopathy: History, Examination, and Testing

Part 3: Cardiomyopathy: Epidemiology, Etiology, and Pathophysiology