Driscoll Children’s Hospital, Corpus Christi, Texas, USA
Clinical History
A 17-year-old male patient was referred to our electrophysiology clinic for evaluation of polymorphic premature ventricular complexes (PVC) and non-sustained ventricular tachycardia (NSVT). He was hospitalized at a remote community hospital 2 years prior with chest pain and mild troponin elevation (troponin I 0.15 ng/ml, normal range 0-0.034 ng/ml). His transthoracic echocardiogram (TTE) at that time demonstrated mild left ventricular (LV) dilatation and mild systolic dysfunction (left ventricular ejection fraction (LVEF) 50%). His initial electrocardiogram (ECG) showed polymorphic PVC with right bundle branch block (RBBB) morphology (Figure 1) and NSVT on telemetry. CMR was performed, which was reported as mild LV dilatation with left ventricular end-diastolic volume index (LVEDVI) of 136 ml/m2, mildly depressed systolic function with a LVEF of 44%, diffusely increased signal on T2 weighted imaging, and no hyperenhancement on late gadolinium enhancement (LGE) imaging. He remained hemodynamically stable and did not require intensive care admission. He was treated with intravenous immunoglobulin for presumed myocarditis and discharged home on metoprolol 25 mg after the troponin started trending down (0.067 ng/ml at discharge) and his symptoms resolved. During his out-patient follow up visits, he continued to have ventricular systolic dysfunction, PVC, and NSVT on serial Holter monitors (Figure 2), prompting electrophysiology referral. He reported no complaints of chest pain, palpitations, syncope, or exercise intolerance. He played basketball regularly.
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Figure 1. Initial 12 lead ECG showing PVC with RBBB morphology. |
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Figure 2. Holter monitor tracing showing PVC and NSVT. |
Upon review of his prior CMR by our imaging team, he was noted to have prominent trabeculations in the LV apex and lateral wall, mildly depressed systolic function, and evidence of subendocardial scar in the basal and mid inferior and lateral wall of the LV (Figures 3 and 4), raising suspicion for an ischemic etiology. Due to persisting arrhythmia and LV systolic dysfunction, he was subsequently admitted electively in stable condition to our hospital for a complete work up. His resting ECG showed polymorphic PVC with a left bundle branch block (LBBB) pattern (Figure 5). He underwent a repeat CMR to evaluate myocardial viability in the setting of previous evidence of LGE.
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| Figure 3. Balanced steady state free precession (bSSFP) imaging showing short axis apical LV with prominent trabeculations. | |
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| Figure 4. Basal and mid short axis (A-C) and four chamber (D) phase sensitive inversion recovery (PSIR) images from initial CMR showing dense subendocardial LGE in the basal inferior and lateral wall and patchy, mid-myocardial non-ischemic LGE in the basal inferoseptal wall. |
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| Figure 5. Resting 12 lead ECG during recent hospital showed PVC with a LBBB pattern. |
CMR Findings
CMR was performed on 1.5 Tesla Ingenia Scanner (Philips Healthcare, Best, The Netherlands). Most recent CMR demonstrated mildly dilated LV with LVEDVI of 121 ml/m2 and LVEF of 49%, akinetic basal inferior and lateral wall of LV, prominent trabeculations in the LV apex and lateral wall on cine bSSFP imaging (Movie 1). No perfusion defects were noted on dynamic first pass perfusion imaging at rest. PSIR imaging showed dense subendocardial LGE in the basal- and mid- inferior and lateral wall, corresponding to the right coronary artery (RCA) distribution (Figure 6). There was also patchy, mid-myocardial non-ischemic LGE in the basal septal wall.
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| Movie 1. Cine bSSFP four chamber (A) demonstrating prominent trabeculations with a non-significant ratio of non-compacted:compacted myocardium that was <2.3, and the basal short axis (B) showing mildly decreased systolic function with hypokinesia of the basal inferior and lateral wall. |
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| Figure 6. Basal (A), mid (B), and apical (C) short axis stack and four chamber (D) PSIR images demonstrate dense subendocardial LGE in the basal inferior and lateral wall and patchy mid-myocardial non-ischemic LGE in the basal inferoseptal segment. |
Conclusion
He underwent a coronary computed tomography angiography (CorCTA), which demonstrated anomalous aortic origin of right coronary artery (AAORCA) from left sinus with anatomic features associated with ischemia: slit-like orifice, acute angle take-off, an extremely narrow and long intramural course, measuring ~ 17 mm and a right dominant coronary circulation (Figure 7). He underwent an exercise stress test, which showed significant ST depression in the inferior and lateral leads (4-5 mm) with reciprocal ST elevation in the anterior leads (2-3 mm) at peak exercise (Figure 8). ST segment changes recovered progressively during the observed 10 minutes into recovery. Genetic testing revealed a PRDM16 variant of unknown significance (VUS) associated with LV non-compaction/dilated cardiomyopathy and a CACNA1C VUS associated with Brugada syndrome and Timothy Syndrome long QT type 8. Due to his history and documented NSVT, he was initiated on sotalol for antiarrhythmic management.
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| Figure 7. CorCTA axial plane (A) and 3D reconstruction (B) demonstrates AAORCA with a long intramural course. |
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| Figure 8. ECG tracings during exercise stress test showing ST depression in the inferior and lateral leads (4-5 mm) with reciprocal ST elevation in the anterior leads (2-3 mm) at peak exercise. |
Due to evidence of inducible ischemia on exercise stress test, he underwent unroofing of the RCA with good antegrade flow post-operatively. He had an uneventful post-operative course, however continued to have LBBB (Figure 9) and polymorphic PVC. Sotalol was continued, and guideline-directed medical therapy was initiated, including Entresto, Farxiga, and eplerenone. He underwent automatic implanted cardiodefibrillator (ICD) a week after his coronary artery surgery because of a combination of NSVT, and ischemic scar, which is an arrhythmogenic substrate predisposing him to sudden cardiac death (SCD). He continues to have mild LV systolic dysfunction (LVEF 45-50%) on his most recent TTE. He will undergo a follow up CorCTA 3-6 months after surgery.
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| Figure 9. Post-op 12 lead ECG demonstrated rare PVC and LBBB. |
Perspective
This case illustrates a delayed diagnosis of AAORCA, presenting with chest pain, mild troponin elevation, mild LV systolic dysfunction, ventricular arrhythmia, prior myocardial infarction and conduction abnormalities. Chest pain is a common complaint in children and cardiac etiology is quite rare but potentially life threatening.[1] This patient’s age made myocarditis the most likely presenting diagnosis and led to appropriate referral for initial CMR. Subendocardial scar on the initial CMR should have raised suspicion for a coronary issue but there was an unfortunate delay of diagnosis because of failure to recognize the ischemic scar pattern on his initial CMR at the outside hospital. Subendocardial LGE results most commonly from ischemic injury. Far less commonly, subendocardial LGE may result from vasculitis, eosinophilic myocarditis, or severe non-ischemic injury with transmural involvement, such as immune mediated and giant cell myocarditis.[2] CorCTA or invasive angiogram after the initial CMR may have facilitated prompt diagnosis given the evidence of prior myocardial infarction.
Myocardial fibrosis from repeated ischemic events in the RCA territory significantly increases the risk of SCD. The combined presence of prior infarct combined with young age, ventricular arrhythmia, and genetic abnormalities of unknown prognostic impact, led to shared decision of ICD placement. A large registry of SCD in young athletes, anomalous coronary arteries from the wrong sinus were associated with 17% of the sudden deaths (3). The causal relationship of AAORCA with SCD in many cases cannot be established, particularly in the presence of coronary artery disease, other structural abnormalities and identified congenital and genetic abnormalities. AAORCA are more common among patients with genetic syndromes, such as tetralogy of Fallot that may play the true causal role in SCD, and the inability to consistently demonstrate ischemia with all AAORCA combined with the high prevalence of incidental AAORCA identified in asymptomatic, even elderly patients has led some cardiologists to propose that most AAORCA are clinically benign.
The commonality of variations of coronary anomaly noted in approximately 1% of CorCTA despite the rarity of SCD indicates most AAORCA do not result in morbidity or mortality. Thus, the optimal management of AAORCA is debated, although observation, medical therapy, angioplasty, stent and surgical unroofing or reimplantation have all been reported in the medical literature. A large database review of 5100 consecutive cases of SCD revealed anomalous coronary artery in 0.6% of the cases, of which 37% was due to AAORCA with inter-arterial course.[4] Patients with AAORCA often died during sleep or rest and were much older.[4] Myocardial fibrosis resulted from likely repetitive episodes of ischemia resulting in high-risk substrate for arrhythmias.[4] LV fibrosis was noted in 45% of the AAORCA patients who suddenly died and of those patients, the fibrosis was noted in multiple locations in 40%, lateral segment in 20% and inferiorly in 40%.[4]
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References
- Drossner DM, Hirsh DA, Sturm JJ, Mahle WT, Goo DJ, Massey R, Simon HK. Cardiac disease in pediatric patients presenting to a pediatric ED with chest pain. Am J Emerg Med. 2011 Jul;29(6):632-8. doi: 10.1016/j.ajem.2010.01.011. Epub 2010 Jul 13. PMID: 20627219.
- Li, Jing-Hui & Xu, Xi-Qi & Zhu, Yong-Jian & Cheng, Chun-Yan & Lu, Minjie & Wang, Hong-Yue & Wang, Yi-Ning & Jing, Zhi-Cheng & Zhao, Shi-Hua. (2021). Subendocardial Involvement as an Underrecognized Cardiac MRI Phenotype in Myocarditis. Radiology. 302. 211276. 10.1148/radiol.2021211276.
- Maron B.J., Doerer J.J., Haas T.S., Tierney D.M. and Mueller F.O.: Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980–2006. Circulation 2009; 119: 1085. PMID: 19221222.
- Finocchiaro G, Behr ER, Tanzarella G, Papadakis M, Malhotra A, Dhutia H, Miles C, Diemberger I, Sharma S, Sheppard MN. Anomalous Coronary Artery Origin and Sudden Cardiac Death: Clinical and Pathological Insights From a National Pathology Registry. JACC Clin Electrophysiol. 2019 Apr;5(4):516-522. doi: 10.1016/j.jacep.2018.11.015. Epub 2019 Jan 30. PMID: 31000108.
Case Prepared by:
Eddie Hulten, MD, MPH
Cases of SCMR, Editorial Board Member
Brown University Health Cardiovascular Institute
Rhode Island, the Miriam and Newport Hospitals
Warren Alpert Medical School, Brown University