Endomyocardial biopsy (EMB) can be considered in the setting of suspected myocarditis, cardiac sarcoidosis, and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) to distinguish from other forms of nonischemic cardiomyopathy. Conventional histopathological assessment is performed via myocardial sampling from the interventricular septum to minimize risk of perforation; however, this can result in limited diagnostic sensitivity and high false-negative rates.1 Three-dimensional electroanatomical mapping (EAM) has been shown to improve the diagnostic yield by facilitating localization of diseased myocardial substrate through identification of low-voltage regions and/or regions with abnormal electrogram (EGM) characterization. Although there are clinical, imaging, and electrocardiographic characteristics that can aid in the diagnosis of the myocardial pathologic process, patients do not always present with typical features.
A 44-year-old African American woman was referred to our institution at Saint Luke’s Mid America Heart Institute for further evaluation and treatment of advanced heart failure. She had a long-standing history of uncontrolled hypertension, and was diagnosed in 2016 with nonischemic cardiomyopathy with biventricular systolic dysfunction and a left ventricular ejection fraction (LVEF) of 25%. She had a prior history of ventricular tachycardia for which an implantable cardioverter-defibrillator (ICD) was implanted. Coronary angiography showed no obstructive coronary artery disease (CAD) in the left coronaries and a known, chronically occluded small branch of a non-dominant right coronary artery (RCA) that was collateralized. Functional capacity had decreased significantly over the last year, with marked dyspnea on exertion (<50 ft) and fatigue consistent with American College of Cardiology/American Heart Association Stage D and New York Heart Association Class IIIB heart failure.
Electrocardiography demonstrated sinus rhythm with normal AV conduction, Q waves in lead III, and a right bundle branch block (RBBB)-inferior axis PVC. Cardiopulmonary exercise testing revealed anaerobic status throughout rest, exercise, and recovery with peak oxygen consumption (VO2) of 5.8 mL/kg/min (15% of predicted). The ventilatory equivalent for carbon dioxide (VE/VCO2) slope during exercise was >40. These findings were consistent with severe cardiac limitation with poor prognostic implications.
Cardiac magnetic resonance imaging demonstrated a markedly dilated LV with a left ventricular end-diastolic volume index (LVEDVI) of 126 mL/m2 and LVEF of 28%. The basal to mid septum was akinetic with near transmural late gadolinium enhancement (LGE, Figure 1). A myocardial positron emission tomography (PET) scan was performed, which demonstrated a mismatched defect with mild to moderately decreased perfusion in the basal and mid anteroseptum with mild 18F-Fludeoxyglucose (FDG) uptake in this region. The cardiac standardized uptake value (SUV) was 1.5x the blood pool SUV, which was consistent with borderline pathologic uptake. There was a second small matched defect with decreased perfusion and no pathologic FDG uptake in the apex and distal inferior wall. Calcified left hilar lymph nodes were visualized; however, there was no extracardiac FDG uptake.
Given the inconclusive imaging findings and disproportionate reduction in LVEF and degree of coronary disease, the patient subsequently underwent EAM-guided EMB. The procedure was performed in the cardiac electrophysiology laboratory by both an electrophysiologist (O.K.Y.) and heart failure cardiologist (B.W.S). Vascular access was obtained using ultrasound guidance. A flexible sheath (Agilis NxT Steerable Introducer, 9.5 Fr, Abbott) was inserted in the left common femoral vein. A 10 Fr sheath was also inserted through which an intracardiac echocardiography (ICE) catheter (ViewFlex Xtra ICE Catheter, Abbott) was advanced to the right ventricular basal septum under fluoroscopic and ultrasound guidance. A deflectable Advisor HD Grid Mapping Catheter, Sensor Enabled (Abbott) was advanced to the right ventricle. Three-dimensional EAM (EnSite NavX, Abbott) was performed of the right ventricle under ICE and fluoroscopic guidance. Low voltage and fractionated electrograms were identified on the basal-mid interventricular septum on the electroanatomical map, as shown in the orange and yellow regions (Figures 2 and 3). Reference values for identifying normal endocardial bipolar and unipolar signals were defined as >1.5 and >5.5 mV, respectively. There was a unipolar abnormality also noted in the same region, suggestive of epicardial scar (Figure 2).
An endomyocardial bioptome (Argon Medical Devices) was connected to the EAM system with the cathode attached at the bioptome tip, and the EAM system reference patch was used as the anode to allow for visualization of the bioptome and recording of EGMs. The mapping catheter was replaced with the bioptome, and it was carefully advanced under ICE and EAM guidance to the region of interest in the basal interventricular septum. The bioptome jaws were closed on the endomyocardial tissue, and this was confirmed by ICE. A total of 4 biopsy samples were performed at sites along the region of interest (Figure 2, asterisks). Histopathological analysis demonstrated nonspecific diffuse fibrosis without evidence of active myocarditis, cardiac sarcoidosis, or other infiltrative processes.
This case demonstrates that EAM-guided EMB is a safe, efficient, and feasible strategy when a diagnosis remains inconclusive based on clinical and imaging characteristics. Both unipolar and bipolar low-voltage regions identified in the basal interventricular septum by EAM were consistent with the near transmural LGE observed in the same region by CMR (Figure 1). Although we did not yield a specific diagnosis in this case, the lack of one is equally important given the therapeutic and prognostic implications. This patient’s basal interventricular septal scar is likely due to the chronic total occlusion of the distal RCA. Although there was no history of paroxysmal atrial fibrillation, it remains a suspicion.
Our purpose in sharing this case is to highlight an uncommonly used tool to potentially augment and aid in a diagnostic yield. While a specific diagnosis was not achieved in this case, it does not undermine the potential benefit of EAM-guided EMB. In fact, over 70% of nonischemic cardiomyopathies do not reveal a specific etiology.
Previous studies have shown that presence of an endocardial unipolar abnormality has been associated with increased sensitivity and specificity for diagnosis of pathologic processes.1,2 Unipolar diseased regions are significantly larger than bipolar regions, and thereby allow for a larger target area where a diagnostic sample may be obtained. The clinical impact is significant for certain diseases, such as ARVD/C with epicardial involvement.
A systematic review of 17 studies demonstrated a pooled sensitivity and specificity of 92% and 58% on per-biopsy analyses for the diagnosis of infiltrative cardiomyopathies (eg, ARVC, sarcoidosis, myocarditis).1 There were 3 pericardial effusions and 1 vascular injury amongst 148 patients. It is important to note that there are no randomized studies comparing the sensitivity or diagnostic yield of conventional EMB to EAM-guided EMB.
We found the use of ICE imaging valuable to ensure optimal contact and retrieval of the endomyocardial tissue. As previously published3, the addition of an EAM system to the bioptome tip further allows recording and visualization of the tip on the mapping system, allowing accurate sampling of the region of interest. Leveraging the expertise and skillset of both a cardiac electrophysiologist and heart failure specialist as co-operators may contribute to both the safety and diagnostic yield of EAM-guided EMB.
Disclosures: The authors have no conflicts of interest to report regarding the content herein.
- Vaidya VR, Abudan AA, Vasudevan K, et al. The efficacy and safety of electroanatomic mapping-guided endomyocardial biopsy: a systematic review. J Interv Card Electrophysiol. 2018;53(1):63-71. doi: 10.1007/s10840-018-0410-7
- Casella M, Pizzamiglio F, Dello Russo A, et al. Feasibility of combined unipolar and bipolar voltage maps to improve sensitivity of endomyocardial biopsy. Circ Arrhythm Electrophysiol. 2015;8(3):625-632. doi: 10.1161/CIRCEP.114.002216
- Konecny T, Noseworthy PA, Kapa S, et al. Endomyocardial biopsy-integrating electrode at the bioptome tip. Ther Adv Cardiovasc Dis. 2015;9(3):66-69. doi: 10.1177/1753944715574660