Primary Endocardial Fibroelastosis Presenting in a Young Child as Incessant Ventricular Tachycardia and Dilated Cardiomyopathy

Abstract

Endocardial fibroelastosis is a cardiomyopathy not commonly seen in the present age. We describe the case of a 4-year-old girl who presented with sustained incessant ventricular tachycardia, a severely dilated left ventricle, and cardiac dysfunction refractory to all medical management and even to ablation; she eventually underwent cardiac transplantation. The diagnosis was made only after histopathologic examination of the explanted heart showed clear evidence of endocardial fibroelastosis. Through this report, we would like to highlight the fact that primary endocardial fibroelastosis can masquerade as idiopathic dilated cardiomyopathy and that associated frequent premature ventricular contractions and nonsustained ventricular tachycardia require close monitoring. Progressive ventricular dilation and ventricular dysfunction can convey a poor prognosis. Sustained recalcitrant ventricular tachycardia in these patients can be a life-threatening event that requires emergent mechanical support and heart transplantation.

Endocardial fibroelastosis (EFE) is characterized by diffuse thickening of the ventricular endocardium and by associated myocardial dysfunction. It can be primary (idiopathic) or secondary to structural heart diseases.^1,2 In infancy or early childhood, this progressive process usually results in heart failure. There have been rare associations with conduction disturbances, atrial fibrillation, and ventricular ectopia.² Sustained ventricular tachycardia (VT) has not been reported. We report an unusual case of a 4-year-old girl who presented with incessant VT refractory to pharmacotherapy and intracardiac ablation. Further hemodynamic deterioration required extracorporeal membrane oxygenator (ECMO) support and eventual heart transplantation. After transplantation, histopathology of the explanted heart revealed the underlying diagnosis of primary EFE.

Case Report

In August 2009, a 4-year-old girl presented at our emergency department with a 1-week history of weakness, emesis, and loss of appetite. On the day of admission, her mother noticed shallow breathing, pallor, and lethargy. The family history was noncontributory. There was no history that suggested sepsis or myocarditis. Although the patient's history was pertinent for premature ventricular contractions (PVCs) and ventricular bigeminy detected soon after birth, the results of an initial cardiac evaluation, including an echocardiogram and Doppler study, were reported to be normal. Holter monitoring at 16 and 42 months of age showed runs of nonsustained VT for which the patient was initially treated with β-blockade therapy (discontinued a year before her current presentation). An echocardiogram done at 42 months of age showed mild to moderate enlargement of the left ventricle (LV) with normal function.

In the emergency department, she was afebrile, alert, and oriented, but pale. Her heart rate was 160 beats/min; she was tachypneic with mild retractions, her blood pressure was 97/66 mmHg, and her oxygen saturation was 98% on 50% forced inspiratory oxygen. She had normal distal pulses with good peripheral perfusion. Cardiac evaluation revealed normal heart sounds and no murmur. The lungs were clear to auscultation and the liver was palpable 3 cm below the costal margin. All her baseline laboratory studies, including complete blood count and chemistry panel, were normal. The blood gas on admission showed no metabolic acidosis. Chest radiography showed cardiomegaly and mild pulmonary vascular congestion. Her electrocardiogram (ECG) showed a monomorphic VT with right bundle branch block morphology and a superior QRS axis (Fig. 1) suggestive of LV fascicular focus. After the failure of adenosine to terminate the rhythm, an esmolol infusion was begun. The initial echocardiogram showed a significantly dilated LV (5.1 cm) with severely depressed function (shortening fraction, 0.10) (Fig. 2).

Fig. 1 Electrocardiogram at presentation reveals wide QRS tachycardia at 160 beats/min, with superior axis and right bundle branch block morphology. Note also that atrioventricular dissociation is evident, with P waves visible, independent, and slower than the QRS rate (arrows).

Fig. 2 Echocardiograms. A) Parasternal short-axis view shows a dilated left ventricle with fractional shortening of 0.10 and no evidence of echo brightness. B) Apical 4-chamber view shows a dilated left ventricle and left atrium, with no evidence of echo brightness of the left ventricle.

She was admitted to the pediatric intensive care unit with the presumptive diagnosis of a tachycardia-induced cardiomyopathy. Intravenous inotropic and ventilatory support were initiated. Over the next 3 days, pharmacotherapy in the form of amiodarone and phenytoin infusions failed to terminate her abnormal rhythm. It was thought that an intracardiac electrophysiologic study (EPS)—with attempted ablation to terminate VT—would be required. As a precaution against the potential provocation (via ablation) of ventricular fibrillation in a patient with depressed myocardial function, she was electively placed on ECMO before the invasive study. The EPS identified an arrhythmogenic focus on the LV septum, just inferior to the septal leaflet of the aortic valve. Radiofrequency ablation terminated the tachycardia. Post-ablation cardiac stimulation failed to re-induce any arrhythmias. The ECMO support was discontinued the next day. However, her rhythm reverted to sustained VT within 24 hours, despite continued pharmacotherapy—now with the addition of verapamil. The ECMO was re-initiated 4 days after ablation because of progressive hemodynamic deterioration. On day 15 of admission, she received a heart transplant. She was in sinus rhythm after transplantation, recovered uneventfully, and was discharged from the hospital 16 days after transplantation.

Pathologic examination of her explanted heart revealed characteristic EFE. Gross examination showed cardiomegaly (135 g, expected 73 g) with a globular appearance. There was marked dilation of both ventricles and mild LV hypertrophy. The LV showed a white plaque-like thickening of the endocardial surface, which was particularly prominent on the septal side (Fig. 3A). No structural abnormalities were noted. Microscopic examination showed markedly diffuse endocardial thickening with lamellar deposition of elastic and fibrous tissue in the LV and interventricular septum (Fig. 3B–D). There were patchy areas of subendocardial fibrosis (Fig 3C–D), with no evidence of myocardial fibrosis, myocarditis, or myocardial fiber disarray. This supports the diagnosis of primary EFE.

Fig. 3 A) Gross appearance of the explanted heart shows marked dilation and mild hypertrophy of the left ventricle. The ventricular septum is opaque and creamy white. B) Histologic microscopy of the left ventricular wall shows pronounced endocardial thickening (arrow) and areas of subendocardial fibrosis (arrowheads). H & E, orig. ×4. C) Microscopy shows laminar deposition of elastic fibers (arrowhead). Elastin stain, orig. ×4. D) Microscopy reveals laminar deposition of collagen fibers (arrow) and areas of subendocardial fibrosis (arrowheads). Trichrome stain, orig. ×4.

Discussion

Endocardial fibroelastosis is characterized by diffuse thickening of the ventricular endocardium due to proliferation of fibrous and elastic tissue and subsequent myocardial diastolic dysfunction.³ It can be primary or secondary to structural heart diseases such as hypoplastic left heart, aortic stenosis, or atresia.³ Pathologically, there are 2 types of EFE: a dilated form (primary EFE) and a contracted form that is a feature of secondary EFE.^4,5 Several authors have argued that endocardial fibroelastosis is a process, rather than a disease in itself, and that it almost always is preceded by a reactive or inflammatory insult, such as a viral infection, which is responsible for the observed pathologic changes.^3,6,7 The common presentation in infants and young children is congestive heart failure. Few cases have been described in which older children, adolescents, or even adult patients who present with cardiac failure have been diagnosed with EFE.⁸ There have been reports, however, of infants and children with EFE who present with conduction disturbances and arrhythmias, including first-degree heart block, atrial fibrillation, nodal tachycardia, and frequent PVCs.² Ours appears to be the first report in the literature that describes a young child with primary EFE who presented with severe ventricular dilation, dysfunction, and incessant VT.

Isolated monomorphic PVCs are a common occurrence and are considered benign in infants and children with structurally normal hearts.⁹ Our patient had neonatal monomorphic PVCs with normal results of an initial cardiac examination and echocardiogram. Subsequent clinical evaluations with ECG and event recordings showed intermittent nonsustained VT. Her echocardiogram at 3.5 years of age showed mild to moderate LV enlargement. This suggested the possibility of an occult cardiomyopathy or familial arrhythmia. The ECG, family history, and routine physical evaluation, however, were not indicative of any identifiable disorder. Several studies have shown that prolonged periods of frequent PVCs and nonsustained VT, even in asymptomatic individuals, can lead to ventricular enlargement and subsequent dysfunction.^10,11 This raised the question of causation: was the observed LV enlargement primary (from an underlying cardiomyopathy) or secondary (from ventricular arrhythmias)? It might not be possible to decipher cause and effect when dilated cardiomyopathy with ventricular dysfunction presents simultaneously with VT. However, the course of events in our patient suggested that the LV enlargement and dysfunction were secondary to ventricular arrhythmia, which led us to a presumptive diagnosis of VT-induced cardiomyopathy.

Successful treatment of ventricular tachycardia has been shown to reverse ventricular dysfunction in adults and children.^12–14 In our patient, the ECG revealed persistent sustained VT arising from the left fascicular focus (Fig. 1). This pattern of VT is similar to that of Belhassen tachycardia (idiopathic fascicular ventricular tachycardia, or reentrant left ventricular tachycardia), which is uncommon in children. Belhassen tachycardia is believed to be sensitive to verapamil and adenosine.¹⁵ Despite radiofrequency ablation and maximal medical management with antiarrhythmia medications—including amiodarone, phenytoin, esmolol, verapamil, and adenosine—our patient had sustained VT. This favored the position that underlying occult cardiomyopathy with progressive ventricular dysfunction was the plausible mechanism for VT. Conversely, study of the heart after explantation showed surprising and distinct evidence of EFE (Fig. 3). Eventually, primary EFE was believed to be responsible for the observed progressive dilated cardiomyopathy, ventricular dysfunction, and recalcitrant VT.

The described case is unusual in a variety of ways. Primary EFE in an older child is rarely seen in this age of widespread vaccination.³ Cases of EFE from mumps infection in utero have become so rare, due to the almost universal use of the MMR (measles, mumps, and rubella) vaccine, that lack of familiarity and very low probability virtually exclude this diagnosis from consideration. Not surprisingly, we did not entertain the diagnosis until analysis after cardiac explantation.

In their study of 64 children with both myocarditis and EFE, Hutchins and Vie¹⁶ found, in patients with short duration of illness, diffuse interstitial myocarditis with variable focal areas of myocardial necrosis; in illness of several weeks' duration, the authors observed subsiding myocarditis and progressive formation of elastic fibers in thickened endocardium. Moreover, in patients with prolonged illness of many months' duration, there was absence of (or trivial) myocarditis, along with thickened endocardium containing elastic lamellae, which suggested interstitial myocarditis as a possible precursor of primary EFE.¹⁶

In our patient, viral polymerase chain reaction studies were not performed on tissue samples. However, the absence of myocardial fiber disarray and inflammatory cells excluded cardiomyopathy and acute myocarditis as causal factors. The clinical course and presentation in our patient did not overtly suggest a history of myocarditis, although subclinical or subacute myocarditis in infancy or early childhood could not be ruled out. Also, the histopathologic changes in our patient were similar to those in Hutchins and Vie's prolonged-illness group of patients¹⁶ with myocarditis—which again suggests the possibility of long-standing myocarditis as a precursor to EFE.

Heart failure with dilated cardiomyopathy is a common feature in these patients. However, to our knowledge, sustained or relcalcitrant VT with primary EFE has not been described. Perhaps the progressive ventricular dilation and dysfunction observed in our patient—in the presence of PVCs and nonsustained VT, culminating in sustained VT—characterizes the natural progression of primary EFE.

Our case also highlights the fact that a cardiac echocardiogram might not be a sensitive diagnostic test for EFE. Neither echo brightness nor LV dimensions can reliably predict the presence of EFE.^17,18 There was no evidence of echo brightness on our patient's echocardiogram (Fig. 2A and 2B). Electron-beam computed tomography and magnetic resonance imaging (this last using perfusion and myocardial delayed-enhancement sequences) have both proved helpful in providing accurate diagnosis before invasive histopathologic testing.^8,19 Whether all patients with idiopathic dilated cardiomyopathy and ventricular dysfunction require noninvasive analysis or invasive histopathologic testing for definitive diagnosis of EFE remains to be determined. If the condition is diagnosed before the need for cardiac transplantation, endocardial stripping is another method of treatment in these patients.

Our case stresses the importance of close monitoring of patients with idiopathic dilated cardiomyopathy and ventricular dysfunction associated with arrhythmias. In the presence of underlying EFE, ventricular arrhythmias with progressive ventricular dilation and dysfunction carry a poor prognosis. As illustrated in this case, sustained recalcitrant VT in these patients can be life threatening.

Conclusion

These days, primary endocardial fibroelastosis is uncommon. Even so, there is the need to be cognizant that EFE can present as an idiopathic dilated cardiomyopathy. Of more importance is the fact that associated PVCs and nonsustained ventricular tachycardia warrant close monitoring for progressive cardiac dysfunction. Sustained refractory VT might be an end-stage disease that requires mechanical support and heart transplantation.