An infant case of double-chambered left ventricle with extensive non-compaction revealed by intraoperative endoscopy

Abstract

Coexistence of double-chambered left ventricle (DCLV) and left ventricular non-compaction (LVNC) is exceptionally rare and may present diagnostic challenges. We report a case of an 8-month-old girl who developed severe heart failure due to the combination of these two conditions. Transthoracic echocardiography revealed left ventricular dilatation and hypokinesia, consistent with a dilated cardiomyopathy-like phenotype, together with a septum-like structure dividing the cavity and swirling flow, raising suspicion of DCLV, although hyper-trabeculation could not be fully assessed. Because of persistent heart failure, a left ventricular assist device (LVAD) was implanted as a bridge to transplantation. Intraoperative endoscopy during LVAD implantation revealed a shelf-like septal partition, extensive non-compacted myocardium, and multiple fibromuscular string-like structures. Histopathology of the resected wall demonstrated preserved three-layered myocardium with endocardial fibroelastosis, intratrabecular sinusoids, and subendocardial fibrosis, consistent with LVNC. To our knowledge, this is the first report of infantile-onset heart failure due to combined DCLV and LVNC confirmed by detailed perioperative imaging and histopathology. This case highlights the morphological overlap between DCLV and LVNC and underscores the value of intraoperative endoscopic and histological evaluation when conventional imaging fails to adequately characterize complex ventricular morphology.

Learning objective

The diagnosis and differential diagnosis of double-chambered left ventricle and left ventricular non-compaction can sometimes be challenging, as their morphology and pathophysiology may overlap. To highlight the diagnostic limitations of conventional imaging in cases with severe cardiac dilation and dysfunction, and to demonstrate how intraoperative endoscopy and histopathology can offer critical insights into rare congenital cardiomyopathies.

Introduction

A double-chambered left ventricle (DCLV) is an extremely rare condition in which the left ventricular cavity is divided into two chambers by an abnormal septum. An abnormal septum can include muscle bundles, membranous structures, fibromuscular ridges, or protruding trabeculations [1]. Left ventricular non-compaction (LVNC), also known as left ventricular hyper-trabeculation, is characterized by excessive trabeculation of the ventricular wall and deep recesses, traditionally interpreted as an arrest of the normal compaction process during embryogenesis. Recent evidence, however, redefines LVNC as a morphological trait appearing in both congenital and acquired settings, not as a single cardiomyopathic entity [2]. The genetic background and clinical features of DCLV and LVNC are varied. We report a case of an infant presenting with severe heart failure due to a combination of these two conditions.

Case report

An 8-month-old girl was referred to our hospital with complaints of a cough for 2 months, dyspnea, as well as facial and lower limb edema. No abnormalities were noted during the perinatal period, and there was no family history of cardiomyopathy, arrhythmia, sudden unexplained death, or congenital anomalies. Her growth and development were good until at least 5 months of age. Upon admission, the patient was afebrile with compensated blood pressure; however, tachycardia and labored breathing were observed. Physical examination revealed a gallop rhythm at the apex of the heart, hepatomegaly, and peripheral coldness in the extremities. Blood cardiac biomarker levels were elevated: creatine kinase-MB 13 IU/L (reference range 0–12), cardiac troponin T 0.198 ng/mL (reference range < 0.1), and N-terminal pro-B-type natriuretic peptide 35,000 pg/mL (reference range 0–55). Microbiological tests, including polymerase chain reaction analyses of serum, pharyngeal mucus, feces, and urine, did not detect any clear pathogens. Chest radiography showed marked cardiomegaly, and the left lung lobe was partially atelectatic with decreased aeration (Fig. 1A).

Fig. 1.

Initial chest radiography and transthoracic echocardiography.

(A) Chest radiograph showing marked cardiomegaly and partial atelectasis of the left lung lobe. (B) Apical 4-chamber view showing left ventricular dilatation, global hypokinesia, and septal-like structures in the left ventricle. Color Doppler flow imaging reveals the blood flow between the two chambers as a whirlpool. (C) In the short-axis view, the left ventricular papillary muscles and mitral valve confirm a normal structure. (D) String-like structure crossing the ventricular septum and the abnormal septum (arrow).

A 12-lead electrocardiogram demonstrated normal sinus rhythm with a QRS duration of 96 ms, without bundle branch block or ventricular pre-excitation. Left ventricular hypertrophy, abnormal Q waves in leads II and aVF, and horizontal ST-segment depression in leads V5 and V6 were noted. Transthoracic echocardiography revealed significant left ventricular dilatation and global hypokinesia, consistent with a dilated cardiomyopathy-like phenotype, together with the following atypical findings: a septal-like structure was observed in the left ventricle, and blood flow appeared to swirl (Fig. 1B). In the short-axis view, normal structure of the papillary muscle was confirmed in the outer cavity (Fig. 1C). The abnormal cavity appeared to contract in synchrony with the left ventricle, without overt mechanical dyssynchrony on visual assessment (Video 1). Additionally, a string-like structure was observed that attached the ventricular septum and the abnormal septum (Fig. 1D). No intra-left ventricle or left ventricular outflow tract obstruction and other cardiovascular malformation were observed. Treatment with diuretics, milrinone, dobutamine, and high-flow nasal cannula was initiated after admission. Severe heart failure symptoms persisted, leading to the decision for left ventricular assist device (LVAD) therapy prior to heart transplantation, and she was transferred to a specialized facility four weeks later.

After the transfer, LVAD (EXCOR, Berlin Heart, Berlin, Germany) implantation was performed. While incising the left ventricular apex to anastomose a 6-mm Berlin Heart inflow cannula, the intracardiac cavity was observed using an endoscope (Fig. 2A, Video 2). The incision site was located on the side of the accessory chamber. The lateral wall of the accessory chamber showed a rugged, non-compacted structure, and thrombi of various sizes were detected. A shelf-like partition wall structure was present between the true and accessory chambers, and multiple string-like structures were observed running from the side of the partition wall to the central partition wall (Fig. 2B and C). A fine, non-compacted structure was also observed around the left ventricular anterior papillary muscle (Fig. 2D).

Fig. 2.

Endoscopic findings of the left ventricular cavity.

(A) Schematic of the left ventricle and accessory chamber. (B and C) The accessory chamber shows a rugged non-compacted structure and thrombi. In addition, shelf-like and string-like structures separating the true left ventricle and the accessory chamber are seen. (D) A fine non-compacted structure is noted around the left ventricular anterior papillary muscle.

Based on these findings, we suspected the coexistence of DCLV and LVNC. The thrombus was removed, and the non-compaction area was resected as much as possible to prevent thromboembolism. Furthermore, to resolve the blood flow disturbance from the mitral valve to the inflow cannula, the shelf-like partition wall and string-like structures were also resected (Online Fig. 1). After LVAD implantation, her heart failure symptoms improved further, and she is awaiting a heart transplant.

Histopathological examination revealed that the myocardium of the accessory chamber showed deep intertrabecular recesses with endocardial fibroelastosis (Fig. 3A). The myocardial cell architecture was preserved (Fig. 3B). Cardiomyocytes showed marked hypertrophy with nuclear hyperchromasia, enlargement, anisokaryosis, and occasional binucleation, accompanied by partial disarray of myocardial fibers (Fig. 3C). The interstitium demonstrated moderate perivascular fibrosis (Fig. 3D) with small muscular arteries in the subendocardial region. The subendocardial interstitium contained intratrabecular myocardial sinusoids associated with prominent elastic fiber.

Fig. 3.

Histopathological features of the accessory chamber wall.

(A) Low-power hematoxylin and eosin (H&E) image shows deep intertrabecular recesses with endocardial fibroelastosis. Scale bar = 500 μm. (B) Elastic van Gieson stain reveals the myocardial middle layer in continuity from the subendocardial to the subepicardial region. The dense circularly oriented myocardial bundles are clearly observed in the central portion, while the outer layer with obliquely arranged fibers is partially visible beneath the subepicardial adipose tissue. Scale bar = 500 μm. (C) Higher-power H&E section highlights hypertrophic cardiomyocytes with nuclear enlargement, anisocytosis, occasional binucleation, and disarrayed fiber alignment. Scale bar = 20 μm. (D) Masson's trichrome staining demonstrates patchy to confluent interstitial and subendocardial fibrosis (blue) intermingled with myocardial fibers (red). Scale bar = 200 μm.

Discussion

The exact etiology of DCLV remains unknown. Previous reports have suggested associations with ischemic insult, viral infection, hypoplasia of regional myocardial intra-trabecular sinusoids, or an intra-myocardial aneurysm during fetal life, and rarely, familial MYH7 gene mutations [3]. Leung et al. [4] proposed that the deficiency of Rac1 in the development of the cardiac septum resulted in a bifid cardiac apex. The clinical features of DCLV vary; some patients present with heart failure at an early age, while others remain asymptomatic until adulthood, and some develop thrombosis or ventricular arrhythmia [3].

As the patient had a broad connection between the left ventricle and the accessory chamber, we also considered ventricular aneurysm to be a differential diagnosis. However, this case has several findings that are inconsistent with left ventricular aneurysm: left ventricular aneurysms often occur in the apex or anterior wall of the left ventricle, and the aneurysm itself is not contractile [5]. Although slight intraventricular timing differences could be appreciated on echocardiography, the QRS duration was narrow (96 ms), and no clear mechanical dyssynchrony suggesting an indication for cardiac resynchronization therapy was identified.

Recent findings indicate that the compact and non-compact layers grow simultaneously; LVNC may reflect dysregulation of endocardial-myocardial signaling pathways (e.g. NOTCH1, vasoendocrine, neuregulin pathways) rather than simple compaction failure [2]. Genetically, pathogenic or likely pathogenic variants are predominantly in sarcomeric genes such as MYH7, MYBPC3, ACTC1, TNNT2, TPM1, and TNNI3. Other implicated loci include TAZ (Barth syndrome), LMNA, DSP, SCN5A, and mitochondrial or X-linked genes [2]. Comprehensive genetic analysis, including familial analysis, has not yet been performed for this patient.

While endoscopy revealed extensive non-compaction in the left ventricle, these findings could not be definitively diagnosed as LVNC based on conventional diagnostic criteria. Generally, diagnostic criteria for LVNC using echocardiography or cardiac magnetic resonance imaging (MRI) include the distance and mass ratio between non-compacted and compacted areas during systole and diastole, as well as color Doppler flow between excessive trabeculation [2]. In our patient, echocardiographic evaluation was inadequate owing to narrow echo windows, reduced contractility, and marked cardiomegaly. Cardiac MRI was not performed before LVAD implantation because of the patient's unstable general condition. This is a limitation of imaging diagnostics, and the involvement of transplant teams may lead to surgeons and pathologists discovering such findings more frequently.

Histological analysis did not confirm the exact composition of the string-like structures, but their morphology was consistent with previously reported left ventricular false tendons (LVFTs). Embryologically, LVFTs are thought to originate from the inner muscle layer of the primitive heart and connect from the ventricular septum to the papillary muscles or free wall of the left ventricle. LVFTs may be associated with left ventricular dysfunction or enlargement, but their etiology and clinical significance remain unclear [6].

Although specific pathological criteria for DCLV and LVNC have not been established, certain aspects proved useful in distinguishing them from other diseases. The preservation of a normal myocardial architecture and the absence of transmural fibrosis or myocardial necrosis argue against an acquired aneurysmal process. In classic LVNC autopsy series, endocardial fibroelastosis or fibrous thickening is frequently described in non-compacted segments [7]. The presence of contractile myocardium and muscular arteries within the subendocardial layer distinguishes this lesion from endocardial fibroelastosis or fibrotic remodeling secondary to ischemic injury. The findings are inconsistent with dilated cardiomyopathy, characterized by diffuse interstitial fibrosis and myocyte attenuation, or arrhythmogenic cardiomyopathy, characterized by fibrofatty replacement [8].

The co-occurrence of myocardial non-compaction, endocardial fibroelastosis, and fibromuscular partition suggests a developmental origin of the abnormality. This aligns with evolving concepts that LVNC is less a degenerative cardiomyopathy and more a manifestation of aberrant embryonic myocardial compaction [2].

To our knowledge, this is the first report of infantile-onset heart failure due to combined DCLV and LVNC. Some consider DCLV to be a subtype of LVNC, and a few adult cases with suspected DCLV and LVNC coexistence have been reported [9], [10]; however, no detailed studies combining morphological, histopathological, and genetic perspectives have been published. The findings in our case may reflect aberrant myocardial trabecular remodeling during fetal development, potentially contributing to chamber segmentation. Chronic and recurrent subendocardial ischemia and fibrotic remodeling, caused by decreased capillary density within areas exhibiting hyper-trabeculation and stasis of intertrabecular blood flow, were considered contributing factors to reduced myocardial contractility. In our patient, the large accessory chamber with extensively non-compacted myocardium likely created an area of relative blood stasis and ineffective intracavitary volume, predisposing to thrombus formation and contributing to progressive ventricular dilatation, even in the absence of overt mechanical dyssynchrony.

DCLV and LVNC can share phenotypic similarities or overlap, and may sometimes be difficult to distinguish. While imaging is an essential part of the diagnosis, endoscopic and histopathological findings in this case provide valuable insights into the etiology and pathophysiology of both conditions. Multifaceted analysis, including genetic testing, and the accumulation of cases are warranted.

Consent statement

Written informed consent was obtained from the patient's parents for the publication of this case report and accompanying images.

Funding

None.

Declaration of competing interest

The authors declare none.

Appendix A. Supplementary data

Online Fig. 1

Schema and endoscopic findings immediately prior to anastomosis with the Berlin Heart inflow cannula.

The accessory chamber is shown after removing the thrombi and resecting the rugged non-compaction area, shelf-like partition, and string-like structure as much as possible.

Video 1

Short-axis view echocardiography scan of the left ventricle and accessory chamber.

Video 2

Endoscopic view of the left ventricle from the accessory chamber.