Deep Intertrabecular Recesses Research Articles

Left Ventricular Non-Compaction in Children: Aetiology and Diagnostic Criteria.

Left ventricular non-compaction (LVNC) is a heterogeneous myocardial disorder characterized by prominent trabeculae protruding into the left ventricular lumen and deep intertrabecular recesses. LVNC can manifest in isolation or alongside other heart muscle diseases. Its occurrence among children is rising due to advancements in imaging techniques. The origins of LVNC are diverse, involving both genetic and acquired forms. The clinical manifestation varies greatly, with some cases presenting no symptoms, while others typically manifesting with heart failure, systemic embolism, and arrhythmias. Diagnosis mainly relies on assessing heart structure using imaging tools like echocardiography and cardiac magnetic resonance. However, the absence of a universally agreed-upon standard and limitations in diagnostic criteria have led to ongoing debates in the scientific community regarding the most reliable methods. Further research is crucial to enhance the diagnosis of LVNC, particularly in early life stages.

Left Ventricle Noncompaction Phenotype: Cause or Consequence?

Abstract Left ventricular noncompaction (LVNC) is commonly described as a congenital cardiomyopathy characterized by prominent myocardial trabeculae and deep intertrabecular recesses extending in the left ventricular chamber. Clinical presentation can differ considerably from asymptomatic individuals to those presenting with heart failure and other serious complications. Diagnosis is usually made by two-dimensional transthoracic echocardiography or cardiac magnetic resonance. Moreover, even if strain parameters are significantly reduced in patients with LVNC, they are not routinely investigated. Here, we report the case of a previously symptomless patient admitted to the hospital for pulmonary edema. Two-dimensional transthoracic echocardiography showed severe valvular heart disease and left ventricle pronounced trabeculation and remodeling, although speckle tracking echocardiography (STE) demonstrated only mild strain reduction. We, therefore, explore the possibility that STE may be useful to differentiate LVNC cardiomyopathy from LVNC phenotype due to severe remodeling.

Myocardial Mechanics and Associated Valvular and Vascular Abnormalities in Left Ventricular Noncompaction Cardiomyopathy.

Left ventricular (LV) non-compaction (LVNC) is a rare genetic cardiomyopathy due to abnormal intra-uterine arrest of compaction of the myocardial fibers during endomyocardial embryogenesis. Due to the partial or complete absence of LV compaction, the structure of the LV wall shows characteristic abnormalities, including a thin compacted epicardium and a thick non-compacted endocardium with prominent trabeculations and deep intertrabecular recesses. LVNC is frequently associated with chronic heart failure, life-threatening ventricular arrhythmias, and systemic embolic events. According to recent findings, in the presence of LVNC, dysfunctional LV proved to be associated with left atrial volumetric and functional abnormalities and consequential dilated and functionally impaired mitral annulus, partly explaining the higher prevalence of regurgitation. Although the non-compaction process morphologically affects only the LV, signs of remodeling of the right heart were also detected. Moreover, dilation and stiffening of the aorta were present. The aim of the present detailed review was to summarize findings regarding changes in cardiac mechanics, valvular abnormalities, and vascular remodeling detected in patients with LVNC.

What can a cryptogenic stroke hide in a young patient?

Abstract Introduction Left ventricular hypertrabeculation is a recently described ventricular phenotype characterized by the alternation of excessive trabeculations with deep intertrabecular recesses that communicate with the left ventricular cavity but not with the coronary circulation. Case presentation We report the case of a young patient, recently diagnosed with ischemic stroke, in whom the cardiological assessment revealed the coexistence of left ventricular hypertrabeculation and dilated cardiomyopathy, which pathologies associated with a high risk of embolic events. The treatment administered followed the therapy for chronic heart failure, control of rhythm disorders that might occur, and the prevention of embolic accidents. Conclusions The particularity of the case is represented by atypical onset through a complication of the disease in a cardiovascular paucisymptomatic patient. Multimodal imaging corroborated with clinical and anamnestic elements had an essential role in the diagnosis.

Role and prognostic relevance of cardiac magnetic resonance imaging in the assessment of left ventricular non-compaction cardiomyopathy: review and meta-analysis

Abstract Background Left ventricular non-compaction (LVNC) is a heterogeneous myocardial disorder characterized by prominent myocardial trabeculation with deep inter-trabecular recesses, thin epicardial layer of compacted myocardium and extensive non-compacted inner muscular layer. Although several diagnostic criteria have been proposed, prediction of major adverse cardiovascular and cerebrovascular events (MACCE) still remains challenging in patients with LVNC. Objectives Objectives of our study were to perform systemic review and meta-analysis of published literature evaluating role and prognostic significance of the late gadolinium enhancement (LGE) in cardiac magnetic resonance imaging (CMR) study, its association with MACCE and characteristics of CMR derived feature-tracking (FT) strain analysis in patients with LVNC. Methods The objectives, literature search strategies, inclusion and exclusion criteria, outcome measurements, and methods of statistical analysis were analyzed according to an established protocol of the cochrane collaboration steps and meta-analysis of observational studies in epidemiology recommendations (MOOSE). Case control studies with evaluated prevalence of LGE in LVNC cardiomyopathy patients with and without MACCE and studies comparing FT strain: left ventricular global longitudinal (LV GLS), global circumferential (GCS) and global radial (GRS) strain between patients with and without LVNC has been included in the analysis. Results A total of 936 papers were collected according to our searching criteria, of those 9 studies including 416 LVNC cardiomyopathy patients with MACCE and 673 LVNC patients without MACCE and with evaluated LGE (including three studies with LVNC and heart failure), also 6 studies including 267 LVNC patients and 283 controls with evaluated FT LV GLS, GCS and GRS (measured in four studies) were selected. LGE was more frequently observed in LVNC patients with MACCE as compared to those without MACCE [RR (95 %CI) 2.52 (1.63 to 3.88); p<0.00001] (Fig.1). FT LV GLS was significantly more affected in LVNC patients compared to controls (St. mean difference (95 %CI): 1.40 (0.69 to 2.11); p<0.00001], as well as GCS and GRS (Fig. 2). Conclusions In patients with LVNC evaluated with CMR, LGE shows association with adverse cardiovascular and cerebrovascular events. CMR deformation indices: FT LV GLS, GCS, and GRS are significantly affected in patients with LVNC as compared to controls. This new CMR technique may be a complementary tool for timely detection and differentiation of LVNC cardiomyopathy and to avoid life threatening adverse events.Figure 1Figure 2

Cardiomyopathy Following Biventricular Noncompaction

Myocardial noncompaction (NC) is usually seen isolated; however, sometimes other congenital heart abnormalities may accompany the myocardial noncompaction. Left ventricular noncompaction (LVNC) is a genetic anomaly where the ventricular wall is replaced by thick ventricular trabeculations with deep intertrabecular recesses held together by a thin compacted layer. The most common site of involvement is the left ventricle, with right ventricular involvement being reported in a few cases. Isolated right ventricular noncompaction (RVNC) is rare yet life-threatening if left untreated. Genetic testing may identify possible mutation of gene. Early diagnosis of NC is very important for disease management. The management of associated other cardiac pathologies simultaneously will help improve the symptoms and prognosis in patients with noncompaction. Here we report a case of 60-year-old male patient presenting with heart failure due to cardiomyopathy with biventricular noncompaction. The case is being presented as an academic interest. Mugda Med Coll J. 2023; 6(1): 44-47

Abstract P1182: The Genetic Dissection Of Rpl3l As A Causal Gene For Neonatal Dilated Cardiomyopathy And Left Ventricular Noncompaction

Background: Cardiomyopathies are responsible for nearly 10% of cardiac deaths in neonates. Recently, biallelic variants in ribosomal protein L3-like ( RPL3L , NM_005061.2) have been reported in neonates with dilated cardiomyopathy (DCM) and heart failure (HF). This study is aimed to study RPL3L induced genetic pathways and mechanisms involved in the development of DCM. Methods: Whole exome and RNA sequencing, histology, immunohistochemistry, and Western blotting were performed in a human explanted heart. Genetic correlation, expression quantitative trait loci (eQTL) mapping and functional analysis were performed using cardiac gene expression data from the patient as well as human and murine genetic reference populations (GRPs). Results: Two-month-old patient with DCM and HF carrying compound heterozygous RPL3L variants, p.A51T and p.V231F, has been managed on an INTERMACS profile 2 with continuous-flow ventricular assist device and successfully bridged to heart transplantation at the age of 4 months. Morphology of the explanted heart displayed apical deep intertrabecular recesses consistent with left ventricular noncompaction (LVNC). Histology revealed interstitial fibrosis and myocardial hypertrophy. No signs of myocarditis and glycogen or mucopolysaccharides deposits were detected. Immunohistochemistry revealed abnormal clusters of RPL3L protein in the cytosol of cardiomyocytes and disruption of F-actin, Z-disk proteins, MYL4 and dystrophin was evident. In a mouse heart, the Rpl3l level was of 33.45 RPKM, while levels of RPL3L appeared to be 32 RPKM in a human heart compared to its mean expression in other adult tissues of 2.54 (mouse) and 2.36 (human). Systems genetics analysis identified high expression values ranged from 11.31 to 12.16 across murine GRPs of BXD mice with the ~1.8-fold difference. Pathways such as “thermogenesis”, “diabetic cardiomyopathy” and “DCM” significantly associated with RPL3L. e QTL mapping suggested Myl4 (Chr 11) and Sdha (Chr 13) as the upstream regulators of Rpl3l . Conclusions: Compound RPL3L heterozygosity is causal for neonatal DCM and LVNC. The RPL3L is highly expressed in the heart tissue of humans and mice. Genes, Myl4 and Sdha, are strong candidates that regulate expression of Rpl3l in murine heart.

Noncompaction Cardiomyopathy and Embolic Events

Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by prominent ventricular trabeculations and deep intertrabecular recesses. Patients with LVNC have an increased risk of embolic events. The presence of symptoms at the time of diagnosis can be a risk marker for stroke/embolic events. Left ventricular ejection fraction (LVEF), as measured by transthoracic echocardiography and left atrial diameter, has been found to be a significant predictor of systemic embolism in LVNC patients. Furthermore, CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus and stroke or transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65–74 years and sex category [female]) scores were significantly higher in patients with stroke or embolism. Although the difference was not statistically significant, pediatric patients with LVNC combined with other congenital heart defects had more thromboembolic events compared to patients with isolated LVNC. On the other hand, stroke/transient ischemic attacks did not differ significantly between patients with isolated apical LVNC and mid-basal noncompaction. Furthermore, no differences in the prevalence of stroke between the quantiles of the maximal ratio of noncompacted to compacted myocardium have been revealed. Additionally, current data show no association between N-terminal pro-B-type natriuretic peptide levels and stroke/embolic events. Current evidence suggests anticoagulation treatment in LVNC patients with prior embolic events, atrial fibrillation, presence of left ventricular (LV) thrombus, and/or LV dysfunction. In patients with LVNC without a clear indication for anticoagulation, anticoagulant therapy may be considered in patients with CHADS2 score ≥2. More data are needed to identify patients at higher risk of embolic events who will be benefited from anticoagulation treatment.

C16 NONCOMPACTION OF VENTRICULAR MYOCARDIUM AND X–LINKED RECESSIVE ICHTYOSIS

Abstract Noncompact left ventricle is a rare congenital cardiomyopathy characterized by numerous ventricular trabeculae separated by deep intertrabecular recesses. It can occur in isolation or in association with neuromuscular disorders and congenital heart defects. The cause is not known but it is thought to be due to the arrest of the normal maturation process of the myocardium. Among the responsible mutations are taffazzine, ZASP and distrobrevin. It can manifest as left ventricular dilatation and dysfunction, arrhythmias, thromboembolic events, and sepsis. The echocardiogram is the investigation of first choice. Magnetic resonance allows you to more precisely distinguish compact and non–compact layers, thrombi and myocardial fibrosis. Clinical case A 19–year–old patient came for syncope. She presented with midfacial hypoplasia, cupped ears, synophrium, high palate, ichthyosis, small hands, and scarring from Achilles tendon lengthening. She denied a family history of cardiovascular disease and sudden cardiac death. Karyotype analysis showed karyotype 46Y, –X, + der t (X; Y) (p22.2; q11.1), with a chromosome derived from the X;Y translocation (a feature already known in the mother and in several maternal relatives ). Coronary angiography, electroencephalogram and brain MRI were within limits. Echocardiogram and MRI showed non–compact myocardium at the left ventricular apex and mild ventricular dysfunction with areas of anterior and posterior dyssynergia (Fig. 1). The ECG showed high QRS voltages. The Holter ECG showed numerous supraventricular extrasystoles even in pairs and runs, rare PVCs, and nocturnal pauses of up to 3 seconds. The patient underwent genetic screening by NGS for sarcomeric mutations which resulted negative. Subsequent genetic analysis showed deletion in two chromosomal regions that could be interpreted as pathogenic (chromosomal region Xp22.33 containing the SHOX gene and involving the deleted locus in Leri–Weill dyschondrosteosis and in the Xp22.33p22.31 region containing the STS gene involving the locus deleted in X–linked recessive ichthyosis) and a duplication in the chromosomal region Yq11.221q11.23 of uncertain significance. Conclusions After review of the scientific literature, the association of the illustrated complex deletion and translocation with non–compact myocardium represents a new finding, worthy of being explored in genetically affected patients.

A Young Healthy Woman with Supraventricular Tachycardia Reveals an Underlying Left Ventricular Non-compaction Cardiomyopathy: A Rare Case Report

LVNC (left ventricular non-compaction) is a rare congenital cardiomyopathy with a reported incidence of 0.05% in adults. It can occur in isolation or affect both ventricles. It’s characterized by prominent LV trabeculae and deep intertrabecular recesses which are filled with blood from the ventricular cavity without evidence of communication to the epicardial coronary artery system. Frequent premature supra ventricular tachycardia as unique finding in LVNC cardiomyopathy is rare manifestation of this disease. We report a case of a frequent persistent supraventricular tachycardia as first manifestation of a patient with LVNC cardiomyopathy in a young healthy woman who despite radio frequency ablation therapy of the supraventricular tachycardia remains symptomatic. The patient was later placed on medical therapy based on a non-cardio selective beta-blocker with a good clinical outcome without recurrent of supra-ventricular arrythmias.

Left Ventricular Noncompaction Masquerading as Hypertrophic Nonobstructive Cardiomyopathy

A 61-year-old male with no significant medical history presented with dyspnea on exertion for the past 3 months. Clinical examination findings and electrocardiogram showed sinus rhythm and left ventricular hypertrophy. The chest X-ray and basic laboratory tests were within the normal limits. A transthoracic echocardiogram was performed which showed left ventricular wall thickening involving the anterior wall, lateral wall, septum, and inferior wall in the basal, mid, and apical segments. The left ventricular apex showed disproportionately increased thickness. There was no left ventricular outflow tract (LVOT) turbulence or obstruction. Left ventricular angiogram showed prominent trabeculations with deep intertrabecular recesses. LVOT obstruction was ruled out. The patient then underwent cardiac magnetic resonance imaging, which showed features suggestive of left ventricular noncompaction.

416 DESMOPLAKIN CARDIOMYOPATHY PRESENTING WITH CARDIAC ARREST IN A PATIENT WITH MYOCARDIAL NON-COMPACTION AND LEFT ACCESSORY PATHWAY

Abstract Introduction Desmoplakin is a human protein which plays a key role into desmosomes structure. Desmoplakin gene mutations can cause the so-called "desmoplakin cardiomyopathy", a form of arrhythmogenic cardiomyopathy. Its clinical history is characterized by severe ventricular arrhythmias, episodic myocardial injury and left ventricular systolic dysfunction associated with fibrosis. Case Presentation A 12-years-old male came to our inherited cardiomyopathy ambulatory for cardiological evaluation due to a previous history of cardiac arrest when he was infant (30 days newborn) and palpitation. Previous medical history included eczematous dermatitis and occasional hyperglycemia. During cardiological evaluation EKG was unremarkable, echocardiography revealed myocardial noncompaction in apical and mid-ventricular regions of the left ventricle's infero-lateral wall (end systolic ratio 2:1) and evidence of direct blood flow into deep intertrabecular recesses by colour doppler. Due to history of palpitation an EP study was performed that showed a lateral left-sided accessory pathway that was ablated during the same procedure. A genetic molecular analysis with exome sequencing (NGS, next generation sequencing) was performed and revealed a heterozygous genetic variant in DSP (Desmoplakin) gene on chromosome 6 (c.4046 G>A pSer1349Asn). Familiar screening revealed the same genetic variant in his father and his brother, both had no cardiological events. Conclusion Desmoplakin cardiomyopathy may have a severe clinical presentation with cardiac arrest. A multidisciplinary approach is suggested for a tailored management of these patients.

1011 HETEROGENEOUS ARRHYTHMIC PHENOTYPE IN A CASE OF LEFT VENTRICULAR NON COMPACTION CARDIOMYOPATHY

Abstract A young 47 years old female patient was hospitalized in our department for recurrent traumatic syncopal episodes in order to undergo Head Up Tilt Test and Electrophysiology Study (EPS). Her ECG was normal and also transthoracic echocardiography didn't show pathological findings. 24 hour Holter ECG recording showed a short run of polymorphic ventricular tachycardia. Regarding familiar history her mother had died at a young age of sudden death. Head-up tilt test resulted negative for induced-syncope. During hospitalization the patient complained onset of malaise rapidly exiting in syncope: telemetry showed two pauses of 3.8 and 5.1 sec respectively, due to paroxysmal III degree atrio-ventricular block. The day after, the patient underwent electrophysiological study. During programmed ventricular stimulation from RV apex with train and V extrastimolous S1 300 S2 220 induction of syncopal ventricular fibrillation was observed, promptly treated with external DC shock. Cardiac MRI was performed showing diagnostic signs of Left Ventricular non-Compaction Cardiomyopathy. Considering the history of traumatic syncope the patient underwent dual chamber ICD implantation and was discharged. No clinical events in a 6 month follow-up. Genetical analysis was performed and we are waiting for the results. The term left ventricular non-compaction (LVNC) identifies a cardiomyopathy, characterized by intrauterine arrest of the compaction process of the ventricular myocardium during the end of the fourth week, thus leading to the development of prominent trabeculae of the left ventricle, deep intertrabecular recesses and a ventricular wall divider into two different layers of myocardium, the first compact, the other not. This nosological entity is difficult to classify (the European Society of Cardiology considers it as not classifiable among other cardiomyopathies, unlike the American Heart Association) mostly from the point of view of clinical implications, often unpredictable. In fact, we may have completely asymptomatic forms, which, according to some authors, should be considered as normal and completely benign variants, and various manifestations, in which the lack of compaction represents a morphological trait shared by phenotypically distinct forms of cardiomyopathy, such as hypertrophic, dilated and restrictive. LVNC carries an increased risk of ventricular dysfunction resulting in chronic heart failure, thromboembolic events and especially arrhythmic, often ventricular and life-threatening manifestations. A large spectrum of arrhythmias has been observed in patients with non-compact ventricles: in particular, supraventricular and ventricular tachycardias, Wolff-Parkinson-White (WPW) syndrome, but also bradyarrhythmias, which include sinus bradycardia, Sick Sinus Syndrome and various degrees of atrioventricular block, up to complete block. Ventricular tachycardias, including those that progress to ventricular fibrillation, occur in 38–47% of adult patients with LVNC, hence sudden death is often the cause of clinical presentation. Seen the features of the pathology, early diagnosis and family clinical evaluation are necessary aspects in patient management.

A Review of Left Ventricular Non-compaction Cardiomyopathy (LVNC).

Left ventricular non-compaction (LVNC) is a rare congenital phenotype defined by the presence of prominent left ventricular trabeculae, deep intertrabecular recesses (continuous with the ventricular cavity), and a thin compacted layer. The most common presentation of LVNC is dyspnea (60%), followed by palpitations (18%), chest pain (15%), syncope (9%), and prior stroke (3%). LVNC presenting with acute myocardial infarction (MI) has rarely been reported in the literature. A forty-one-years old female presented with substernal chest pain and exertional dyspnea. On physical examination, she was alert without any distress, her lungs and heart examination were within normal limits. Peripheral pulses were palpable and regular, and +1 peripheral pitting edema was noted. EKG showed normal sinus rhythm with premature atrial contractions (PACs), left axis deviation, and ST-segment and T wave changes suggestive of inferior wall ischemia. Troponin I level was found to be elevated, which peaked within 24 hours, Troponinmax 110.08 ng/ml. Transthoracic echocardiography showed moderate LV dilatation with severely reduced EF (15-20%), and diffuse LV hypokinesis with a grade III restrictive pattern. There was heavy trabeculation of LV involving 2/3rd LV endocardium and wall thickness with sinusoidal tunnels perpendicular to LV wall. These morphological findings met the diagnostic criteria of LVNC/NCM. LVNC presenting with acute myocardial infarction (MI) can be related to poor outcomes, however, more data is needed to establish the clinical implication of this presentation. Asymptomatic LVNC can be observed while symptomatic LVNC should be treated with standard guidelines of HF.

The Electrocardiogram in the Diagnosis and Management of Patients With Left Ventricular Non-Compaction.

Left ventricular non-compaction (LVNC) is characterised by prominent left ventricular trabeculae and deep inter-trabecular recesses. Although considered a distinct cardiomyopathy, prominent trabeculations may also be found in other cardiomyopathies, in athletes or during pregnancy. Clinical presentation includes heart failure symptoms, systemic embolic events, arrhythmias and sudden cardiac death. Currently, LVNC diagnosis relies on imaging criteria, and clinicians face several challenges in the assessment of patients with prominent trabeculations. In this review, we summarise the available information on the role of the ECG in the diagnosis and management of LVNC. ECG abnormalities have been reported in 75-94% of adults and children with LVNC. The lack of specificity of these ECG abnormalities does not allow (in isolation) to diagnose the condition. However, when considered in a set of diagnostic criteria including family history, clinical information, and imaging features, the ECG may differentiate between physiological and pathological findings or may provide clues raising the possibility of specific underlying conditions. Finally, some ECG features in LVNC constitute ominous signs that require a stricter patient surveillance or specific therapeutic measures. The ECG remains a cornerstone in the diagnosis and management of patients with cardiomyopathies, including LVNC.

OCCULT NONCOMPACTION CARDIOMYOPATHY LEADING TO CARDIOGENIC SHOCK: AN INFREQUENT YET DEADLY DIAGNOSIS

OCCULT NONCOMPACTION CARDIOMYOPATHY LEADING TO CARDIOGENIC SHOCK: AN INFREQUENT YET DEADLY DIAGNOSIS

Left Ventricular Noncompaction in Children: The Role of Genetics, Morphology, and Function for Outcome.

Left ventricular noncompaction (LVNC) is a ventricular wall anomaly morphologically characterized by numerous, excessively prominent trabeculations and deep intertrabecular recesses. Accumulating data now suggest that LVNC is a distinct phenotype but must not constitute a pathological phenotype. Some individuals fulfill the morphologic criteria of LVNC and are without clinical manifestations. Most importantly, morphologic criteria for LVNC are insufficient to diagnose patients with an associated cardiomyopathy (CMP). Genetic testing has become relevant to establish a diagnosis associated with CMP, congenital heart disease, neuromuscular disease, inborn error of metabolism, or syndromic disorder. Genetic factors play a more decisive role in children than in adults and severe courses of LVNC tend to occur in childhood. We reviewed the current literature and highlight the difficulties in establishing the correct diagnosis for children with LVNC. Novel insights show that the interplay of genetics, morphology, and function determine the outcome in pediatric LVNC.

Tricuspid Annular Abnormalities in Isolated Left Ventricular Non-compaction-Insights From the Three-dimensional Speckle-Tracking Echocardiographic MAGYAR-Path Study.

IntroductionProminent trabecular left ventricular (LV) meshwork and deep intertrabecular LV recesses are featuring LV non-compaction (LVNC). The aim of this study was to evaluate tricuspid annular (TA) morphological and functional abnormalities by three-dimensional speckle-tracking echocardiography (3DSTE) in patients with LVNC without right ventricular (RV) involvement.Materials and MethodsThis study consisted of 21 patients with isolated LVNC, from which 6 cases were excluded due to inferior image quality. The remaining patient group consisted of 15 subjects with a mean age of 52.1 ± 11.4 years (9 males). LVNC was defined according to the Jenni's criteria. Their results were compared to 21 age- and gender-matched healthy controls (mean age: 52.4 ± 3.9 years, 14 males). Complete routine 2-dimensional Doppler echocardiographic examination was performed in all the patients with isolated LVNC and healthy controls. End-systolic and end-diastolic TA dimensions were assessed on selected planes derived from full-volume 3D echocardiographic datasets during 3DSTE.ResultsPatients with isolated LVNC showed significantly dilated end-systolic and end-diastolic TA diameter and area, which were accompanied with preserved TA functional properties and associated with right atrial (RA) volumes. TA plane systolic excursion (TAPSE) showed mild correlations with TA fractional area change (TAFAC) and TA fractional shortening (TAFS). No correlations could be demonstrated between TAPSE and TA morphological features. Extent of LVNC did not correlate with any echocardiographic parameters.ConclusionTA is dilated with preserved sphincter-like function in patients with isolated LVNC. Longitudinal (TAPSE) and sphincter-like (TAFAC and TAFS) TA movements correlate with each other. TA dilation is associated with an increased RA volumes respecting cardiac cycle.

Dilated-Left Ventricular Non-Compaction Cardiomyopathy in a Pediatric Case with SPEG Compound Heterozygous Variants

Left Ventricular Non-Compaction (LVNC) is defined by the triad prominent myocardial trabecular meshwork, thin compacted layer, and deep intertrabecular recesses. LVNC associated with dilation is characterized by the coexistence of left ventricular dilation and systolic dysfunction. Pediatric cases with dilated-LVNC have worse outcomes than those with isolated dilated cardiomyopathy and adult patients. Herein, we report a clinical and genetic investigation using trio-based whole-exome sequencing of a pediatric case with early-onset dilated-LVNC. Compound heterozygous mutations were identified in the Striated Muscle Enriched Protein Kinase (SPEG) gene, a key regulator of cardiac calcium homeostasis. A paternally inherited mutation: SPEG; p.(Arg2470Ser) and the second variant, SPEG; p.(Pro2687Thr), is common and occurred de novo. Subsequently, Sanger sequencing was performed for the family in order to segregate the variants. Thus, the index case, his father, and both sisters carried the SPEG: p.(Arg2470Ser) variant. Only the index patient carried both SPEG variants. Both sisters, as well as the patient’s father, showed LVNC without cardiac dysfunction. The unaffected mother did not harbor any of the variants. The in silico analysis of the identified variants (rare and common) showed a decrease in protein stability with alterations of the physical properties as well as high conservation scores for the mutated residues. Interestingly, using the Project HOPE tool, the SPEG; p.(Pro2687Thr) variant is predicted to disturb the second fibronectin type III domain of the protein and may abolish its function. To our knowledge, the present case is the first description of compound heterozygous SPEG mutations involving a de novo variant and causing dilated-LVNC without neuropathy or centronuclear myopathy.

Clinical Presentation of Left Ventricular Noncompaction Cardiomyopathy and Bradycardia in Three Families Carrying HCN4 Pathogenic Variants.

Background: Left ventricular noncompaction (LVNC) is a genetically and phenotypically heterogeneous cardiomyopathy in which myocardium consists of two, distinct compacted and noncompacted layers, and prominent ventricular trabeculations and deep intertrabecular recesses are present. LVNC is associated with an increased risk of heart failure, atrial and ventricular arrhythmias and thromboembolic events. Familial forms of primary sinus bradycardia have been attributed to alterations in HCN4. There are very few reports about the association between HCN4 and LVNC. The aim of our study was to characterize the clinical phenotype of families with LVNC and sinus bradycardia caused by pathogenic variants of the HCN4 gene. Methods: From March 2008 to July 2021, we enrolled six patients from four families with diagnosed isolated LVNC based on the clinical presentation, family history and echocardiographic and cardiovascular magnetic resonance (CMR) evidence of LVNC. Next generation sequencing (NGS) analysis was undertaken for the evaluation of the molecular basis of the disease in each family. Results: A total of six children (median age 11 years) were recruited and followed prospectively for the median of 12 years. All six patients were diagnosed with LVNC by echocardiography, and five participants additionally by CMR. The presence of late gadolinium enhancement (LGE) was found in three children. Sinus bradycardia and dilation of the ascending aorta occurred in five studied patients. In four patients from three families, the molecular studies demonstrated the presence of rare heterozygous HCN4 variants. Conclusion: (1) The HCN4 molecular variants influence the presence of a complex LVNC phenotype, sinus bradycardia and dilation of the ascending aorta. (2) The HCN4 alteration may be associated with the early presentation of clinical symptoms and the severe course of the disease. (3) It is particularly important to assess myocardial fibrosis not only within the ventricles, but also in the atria in patients with LVNC and sinus bradycardia.