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A neonate born of third-degree consanguineous marriage presented on day 12 of life with congestive cardiac failure. A male sibling died at 3 months of age, cause of which was not known. He was treated with decongestive measures and multiple inotropes. 2D Echocardiogram revealed severe Left ventricular dysfunction with prominent trabeculations and deep recesses in the left ventricle suggestive of Left ventricular non-compaction. He was also found to have horse-shoe kidney. Considering the presence of cardiac left ventricular non compaction, horse-shoe kidney and family history of neonatal death and pregnancy loss clinical exome sequencing was done. It detected a homozygous missense variant in exon 6 of the AGK gene suggestive of Senger’s syndrome. Baby was on regular follow-up and was thriving well on diuretics, sacubitril-valsartan and weekly levosimendan infusions. At 8 months of age, cardiac transplantation was successfully done and baby has been doing well post-transplantation. LVNC in children is rare with an estimated incidence of 0.11 per 100,000, the highest incidence being during infancy. Senger’s syndrome is autosomal recessive in inheritance. Senger’s syndrome associated with Left ventricular non compaction has been reported only once in literature so far. Renal manifestations in the form of horse shoe kidney like in our index baby has not been reported previously with Senger’s syndrome.

A genetic diagnosis of primary cardiomyopathies can be a long-unmet need in patients with complex phenotypes. We investigated a three-generation family with cardiomyopathy and various extracardiac abnormalities that had long sought a precise diagnosis. The 41-year-old proband had hypertrophic cardiomyopathy (HCM), left ventricular noncompaction, myocardial fibrosis, arrhythmias, and a short stature. His sister showed HCM, myocardial hypertrabeculation and fibrosis, sensorineural deafness, and congenital genitourinary malformations. Their father had left ventricular hypertrophy (LVH). The proband's eldest daughter demonstrated developmental delay and seizures. We performed a clinical examination and whole-exome sequencing for all available family members. All patients with HCM/LVH shared a c.4411-2A>C variant in ALPK3, a recently known HCM-causative gene. Functional studies confirmed that this variant alters ALPK3 canonical splicing. Due to extracardiac symptoms in the female patients, we continued the search and found two additional single-gene disorders. The proband's sister had a p.Trp329Gly missense in GATA3, linked to hypoparathyroidism, sensorineural deafness, and renal dysplasia; his daughter had a p.Ser251del in WDR45, associated with beta-propeller protein-associated neurodegeneration. This unique case of three monogenic disorders in one family shows how a comprehensive approach with thorough phenotyping and extensive genetic testing of all symptomatic individuals provides precise diagnoses and appropriate follow-up, embodying the concept of personalized medicine. We also present the first example of a splicing functional study for ALPK3 and describe the genotype–phenotype correlations in cardiomyopathy. [ABSTRACT FROM AUTHOR]

Left ventricular noncompaction cardiomyopathy (LVNC) is a structural heart defect that has been associated with generation of arrhythmias in the population and is a cause of sudden cardiac death with severe systolic dysfunction and fatal arrhythmias. LVNC has gained increasing acknowledgment with increased prevalence. We conducted a systematic review of reported electrocardiogram (ECG) results for pediatric LVNC patients. EMBASE database query was performed, yielding 4531 articles related to LVNC between 1990 and December 2023. Patient age ranged from prenatal to 18 years of age. Qualitative analyses were performed to characterize individual arrhythmias, and summative interpretation of ECG evaluations was gathered for the entire cohort. Systematic review of 57 LVNC cases and ECG presentation revealed many waveform consistencies, including abnormal left ventricular, atrioventricular node, and interventricular septal patterns, and specifically a high incidence of Mobitz type II and Wolff–Parkinson–White waveforms. This review of ECG analysis reinforces the clinical and etiologic significance of pediatric LVNC. While LVNC in pediatric populations may not always present as acute clinical cases, further investigation into the electrophysiology of the disease supports the need for further evaluation and risk stratification for patients with suspected LVNC and/or ventricular arrhythmia. [ABSTRACT FROM AUTHOR]

Background: Left ventricular hypertrophy (LVH) is a well-recognized cardiac dysfunction in infants of mothers with gestational diabetes mellitus (GDM). Left ventricular noncompaction (LVNC) is a cardiomyopathy that is morphologically characterized by numerous prominent trabeculations and deep intertrabecular recesses on cardiovascular imaging. However, there have been no case reports on neonates of mothers with GDM showing LVH and LVNC. Case presentation: A patient, with LVH of a mother with GDM, was delivered at 36 weeks of gestation. Prominent trabeculations in the LV, suggesting LVNC, instead of LVH, were apparent 1 week after birth. A heterozygous deletion variant in the MYH7 gene (NM_000257.4: c.1090T>C, p.Phe364Leu) was discovered through genetic testing using a cardiomyopathy-associated gene panel in the patient and his father and the older brother who had LVNC. The patient is now 5 years old and does not have major cardiac events, although LVNC persisted. This is the first case of LVH secondary to a mother with GDM and LVNC with a novel variant in the MYH7 gene. Conclusion: Genetic testing should be conducted to obtain an accurate outcome and medical care in a patient with LVH and subsequently prominent hypertrabeculation in the LV. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the impact of cardiac magnetic resonance (CMR) on the diagnosis in patients with known or suspected left ventricular noncompaction (LVNC). We retrospectively reviewed the medical charts of 12,811 consecutive patients who had CMR studies between 2008 and 2022 in a large tertiary center. We included patients referred for CMR because of known or suspected LVNC. The study sample consisted of 333 patients, 193 (58.0%) male, median age 39.0 (26.8–51.0) years. Among 74 patients fulfilling the echocardiographic LVNC criteria, the diagnosis was confirmed in 54 (73.0%) cases. In 259 patients with ultrasound-based suspicion of LVNC, CMR led to an LVNC diagnosis in 82 (31.7%) patients. In both groups, CMR led to a new diagnosis in 89 cases (10 (13.5%) and 79 (30.5%)). A quantity of 38 (5.4%) patients were diagnosed with dilated cardiomyopathy, 11 (1.4%) patients were diagnosed with hypertrophic cardiomyopathy, and 21 (4.1%) patients were diagnosed with unclassified cardiomyopathy. In four patients with suspected LVNC, a myocardial trabeculation was a secondary result of dilatation due to coronary heart disease. In five cases, valvular heart disease was found. Four patients were diagnosed with athlete's heart. Other diagnoses (arrhythmogenic right ventricular cardiomyopathy, peripartum cardiomyopathy, hypokinetic non-dilated cardiomyopathy, sarcoidosis, amyloidosis, and ventricular septum defect) were found in six patients. CMR is a valuable tool in the evaluation of cardiac muscle and in differentiating LVNC and other cardiac diseases. [ABSTRACT FROM AUTHOR]

A neonate born of third-degree consanguineous marriage presented on day 12 of life with congestive cardiac failure. A male sibling died at 3 months of age, cause of which was not known. He was treated with decongestive measures and multiple inotropes. 2D Echocardiogram revealed severe Left ventricular dysfunction with prominent trabeculations and deep recesses in the left ventricle suggestive of Left ventricular non-compaction. He was also found to have horse-shoe kidney. Considering the presence of cardiac left ventricular non compaction, horse-shoe kidney and family history of neonatal death and pregnancy loss clinical exome sequencing was done. It detected a homozygous missense variant in exon 6 of the AGK gene suggestive of Senger's syndrome. Baby was on regular follow-up and was thriving well on diuretics, sacubitril-valsartan and weekly levosimendan infusions. At 8 months of age, cardiac transplantation was successfully done and baby has been doing well posttransplantation. LVNC in children is rare with an estimated incidence of 0.11 per 100,000, the highest incidence being during infancy. Senger's syndrome is autosomal recessive in inheritance. Senger's syndrome associated with Left ventricular non compaction has been reported only once in literature so far. Renal manifestations in the form of horse shoe kidney like in our index baby has not been reported previously with Senger's syndrome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction. Left ventricular noncompaction (LVNC) is a rare heterogeneous pathology characterized by a two-layered structure with a predominance of non-compact layer in the form of multiple trabeculations and pockets between them, communicating with the left ventricular cavity. One of the rare LVNC phenotypes is a combination with congenital heart defects, including atrial septal defect (ASD).Brief description. The article presents a case report describing the difficulties of selecting antiarrhythmic therapy in a patient with LVNC and ASD, complicated by arrhythmias due to heart failure. The diagnosis of LVNC was confirmed by the Petersen criterion using magnetic resonance imaging.Discussion. Cardiac arrhythmias in patients with LVNC and congenital heart defects, as a result of both anatomical and hemodynamic causes of electrical heart instability, constitute a danger of thromboembolism and sudden cardiac death, and also contribute to heart failure progression. The case is of interest due to the rare combination of LVNC and ASD, complicated by frequent episodes atrial fibrillation and premature ventricular contractions in the form of parasystoles, as well as difficulties in selecting antiarrhythmic therapy. Pulmonary vein cryoballoon ablation eliminated the source of atrial fibrillation. Ventricular ectopic activity was stopped using the anticonvulsant drug carbamazepine.

A genetic diagnosis of primary cardiomyopathies can be a long-unmet need in patients with complex phenotypes. We investigated a three-generation family with cardiomyopathy and various extracardiac abnormalities that had long sought a precise diagnosis. The 41-year-old proband had hypertrophic cardiomyopathy (HCM), left ventricular noncompaction, myocardial fibrosis, arrhythmias, and a short stature. His sister showed HCM, myocardial hypertrabeculation and fibrosis, sensorineural deafness, and congenital genitourinary malformations. Their father had left ventricular hypertrophy (LVH). The proband’s eldest daughter demonstrated developmental delay and seizures. We performed a clinical examination and whole-exome sequencing for all available family members. All patients with HCM/LVH shared a c.4411-2A>C variant in ALPK3, a recently known HCM-causative gene. Functional studies confirmed that this variant alters ALPK3 canonical splicing. Due to extracardiac symptoms in the female patients, we continued the search and found two additional single-gene disorders. The proband’s sister had a p.Trp329Gly missense in GATA3, linked to hypoparathyroidism, sensorineural deafness, and renal dysplasia; his daughter had a p.Ser251del in WDR45, associated with beta-propeller protein-associated neurodegeneration. This unique case of three monogenic disorders in one family shows how a comprehensive approach with thorough phenotyping and extensive genetic testing of all symptomatic individuals provides precise diagnoses and appropriate follow-up, embodying the concept of personalized medicine. We also present the first example of a splicing functional study for ALPK3 and describe the genotype–phenotype correlations in cardiomyopathy.

Purpose of Review: This article aims to review the accurate classification of non-ischemic cardiomyopathy, including the methods, basis, subtype characteristics, and prognosis, especially the similarities and differences between different classifications. Recent Findings: Non-ischemic cardiomyopathy refers to a myocardial disease that excludes coronary artery disease or ischemic injury and has a variety of etiologies and high incidence. Recent studies suggest that traditional classification methods based on primary/mixed/acquired or genetic/non-genetic cannot meet the precise needs of contemporary clinical management. This article systematically describes the history of classifications of cardiomyopathy and presents etiological and genetic differences between cardiomyopathies. The accurate classification is described from the perspective of morphology, function, and genomics in hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular noncompaction, and partially acquired cardiomyopathy. The different clinical characteristics and treatment needs of these cardiomyopathies are elaborated. Some single-gene mutant cardiomyopathies have unique phenotypes, and some cardiomyopathies have mixed phenotypes. These special classifications require personalized precision treatment, which is worthy of independent research. Summary: This article describes recent advances in the accurate classification of non-ischemic cardiomyopathy from clinical phenotypes and causative genes, discusses the advantages and usage scenarios of each classification, compares the differences in prognosis and patient management needs of different subtypes, and summarizes common methods and new exploration directions for accurate classification. [ABSTRACT FROM AUTHOR]

Overlapping of left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy in the same patient is rare and is associated with a more severe clinical course and unfavorable prognosis. The present report describes the case of a severely regurgitant bicuspid aortic valve in a 68-year-old man with overlapping LVNC and asymmetrical septal hypertrophy. Aortic valve replacement controlled the left ventricular dilatation that occurred secondary to the volume overload induced by the valvular disease. However, even 3 years postoperatively, severe systolic dysfunction persisted due to the preexisting myocardial disease, requiring close and lifelong follow-up with special attention to life-threatening arrhythmias and thromboembolism. [ABSTRACT FROM AUTHOR]

Abstract Left ventricular noncompaction (LVNC) is a heterogeneous disorder with unclear genetic causes. The arhGEF18 gene is a guanine nucleotide exchange factor related to the Rho pathway and a possible predisposing gene for LVNC. In this study, a mouse model of arhGEF18 gene conditional knockout (cKO) in cardiomyocytes was established using the Cre‐LoxP system to provide an animal model for the genetic study of LVNC. ArhGEF18 cKO mice were obtained by crossing arhGEF18f/+/myh6‐Cre+ and arhGEF18f/f mice. The mRNA and protein expression levels of arhGEF18 in different tissues were verified. The myocardial cytoskeleton and polar protein expression, the survival rate, cardiac function, and cardiac histology of model mice were determined. ArhGEF18 cKO mice were successfully established. ArhGEF18 was confirmed to be specifically knocked out in the myocardial tissue of arhGEF18f/f/myh6‐Cre+ mice at the mRNA and protein levels, and the knockout rate was approximately 75%. The relative expression levels of cytoskeleton and cell polarity proteins such as α/β‐tubulin, Scribble, Crb2, and PAR3 in the cKO group were significantly lower than those in the control group (p

BackgroundBecker muscular dystrophy (BMD) is an inherited X-linked recessive condition resulting from mutations of the DMD gene encoding dystrophin. Left ventricular noncompaction (LVNC) is a rare cardiomyopathy morphologically characterized by abnormal myocardial trabeculae and deep recesses in the left ventricle. LVNC in BMD patients has only rarely been reported.Case reportIn the present study, we identified a deletion mutation in exons 10 to 12 (EX10_12 del) of the DMD gene (reference sequence NM_004006.2) in two Chinese siblings with BMD and LVNC by high throughput targeted next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR). The proband was a 22-year-old man admitted with dyspnea, abdominal distention, and polyserositis. It is noteworthy that both the proband and his younger brother manifested progressive muscular atrophy and creatine kinase (CK) elevation. Light and electron microscopy examination of muscle biopsies showed the typical features of dystrophinopathies. Cardiac magnetic resonance imaging and echocardiography demonstrated that both brothers had an enlarged left ventricle, LVNC, and reduced left ventricular ejection fraction. Finally, the proband underwent heart transplantation at age 26 with an event-free follow-up over 4 years post-transplantation.ConclusionThis case further enriches our knowledge of the symptoms, genotype, cardiac performance, management, and prognosis of BMD patients complicated by LVNC. It is recommended that early comprehensive cardiac evaluation should be considered for patients with BMD to exclude LVNC, as this may have a significant impact on their prognosis.

Barth syndrome (BTHS) is an X‐linked disorder characterized by cardiomyopathy, skeletal myopathy, and 3‐methylglutaconic aciduria. The causative pathogenic variants for BTHS are in TAZ, which encodes a putative acyltransferase named tafazzin and is involved in the remodeling of cardiolipin in the inner mitochondrial membranes. Pathogenic variants in TAZ result in mitochondrial structural and functional abnormalities. We report a case of infantile BTHS with severe heart failure, left ventricular noncompaction, and lactic acidosis, having a missense c.640C>T (p.His214Tyr) variant in TAZ, which is considered a pathogenic variant based on the previously reported amino acid substitution at the same site (c.641A>G, p.His214Arg). However, in this previously reported case, heart function was compensated and not entirely similar to the present case. Silico prediction analysis suggested that c.640C>T could alter the TAZ messenger RNA (mRNA) splicing process. TAZ mRNAs in isolated peripheral mononuclear cells from the patient and in vitro splicing analysis using minigenes of TAZ found an 8 bp deletion at the 3′ end of exon 8, which resulted in the formation of a termination codon in the coding region of exon 9 (H214Nfs*3). These findings suggest that splicing abnormalities should always be considered in BTHS. [ABSTRACT FROM AUTHOR]

Patients with two congenital heart diseases (CHDs), Ebstein’s anomaly (EA) and left ventricular noncompaction (LVNC), suffer higher morbidity than either CHD alone. The genetic etiology and pathogenesis of combined EA/LVNC remain largely unknown. We investigated a familial EA/LVNC case associated with a variant (p.R237C) in the gene encoding Kelch-like protein 26 (KLHL26) by differentiating induced pluripotent stem cells (iPSCs) generated from affected and unaffected family members into cardiomyocytes (iPSC-CMs) and assessing iPSC-CM morphology, function, gene expression, and protein abundance. Compared with unaffected iPSC-CMs, CMs containing the KLHL26 (p.R237C) variant exhibited aberrant morphology including distended endo(sarco)plasmic reticulum (ER/SR) and dysmorphic mitochondria and aberrant function that included decreased contractions per minute, altered calcium transients, and increased proliferation. Pathway enrichment analyses based on RNASeq data indicated that the “structural constituent of muscle” pathway was suppressed, whereas the “ER lumen” pathway was activated. Taken together, these findings suggest that iPSC-CMs containing this KLHL26 (p.R237C) variant develop dysregulated ER/SR, calcium signaling, contractility, and proliferation. NEW & NOTEWORTHY We demonstrate here that iPSCs derived from patients with Ebstein’s anomaly and left ventricular noncompaction, when differentiated into cardiomyocytes, display significant structural and functional changes that offer insight into disease pathogenesis, including altered ER/SR and mitochondrial morphology, contractility, and calcium signaling. [ABSTRACT FROM AUTHOR]

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.

Abstract Background Cardiac magnetic resonance (CMR) has been used to diagnose and risk-stratify patients with left ventricular noncompaction (LVNC). The prognostic value of CMR parameters for LVNC, especially feature tracking (CMR-FT), is not well known in LVNC patients with left ventricular dysfunction. The present study aimed to investigate whether the combination of CMR-FT with traditional CMR parameters can increase the prognostic value of CMR for LVNC patients with reduced left ventricular ejection fraction (LVEF). Methods A total of 123 candidates were retrospectively included in this multicenter study and 55 LVNC patients (mean age, 45.7 ± 16.2 years; 61.8% men) remained after applying the exclusion criteria. Clinical features, left ventricular (LV) function parameters, global and segment myocardial strain, and late gadolinium enhancement (LGE) were evaluated. The outcomes include the composite events of cardiovascular death, heart transplantation, hospitalization for heart failure, thromboembolic events, and ventricular arrhythmias. Results After a median follow-up of 5.17 years (interquartile range: 0.17 to 10.58 years), 24 (36.8%) patients experienced at least one major adverse cardiovascular event (MACE). The myocardial strain parameters of patients with events were lower than those of patients without events. In the univariable Cox analysis, LVEF, the presence of LGE, global longitudinal strain (GLS) and segmental strains, including longitudinal strain at the apical level and radial and circumferential strain at the basal level, were significantly associated with MACEs. In the multivariate analysis, LGE (hazard ratio (HR) 3.452, 95% CI 1.133 to 10.518, p = 0.029) was a strong predictor of MACEs and significantly improved the predictive value (chi-square of the model after adding LGE: 7.51 vs. 13.47, p = 0.009). However, myocardial strain parameters were not statistically significant for the prediction of MACEs after adjusting for age, body mass index, LVEF and the presence of LGE and did not increase the prognostic value (chi-square of the model after adding GLS: 13.47 vs. 14.14, p = 0.411) in the multivariate model. Conclusions The combination of CMR-FT with traditional CMR parameters may not increase the prognostic value of CMR in LVNC patients with reduced LVEF, while the presence of LGE was a strong independent predictor of MACEs and significantly improved the predictive value.

Background: Left ventricular noncompaction (LVNC) is a heterogeneous myocardial disorder with an uncertain prognosis. There was a lack of studies on LVNC subtypes at present. This study sought to identify the prognosis of the overall population of LVNC and to describe the distribution of different subtypes and compare their prognosis. Hypothesis: Patients with different subtypes of LVNC may have different prognoses. Methods: Patients who fulfilled the Jenni criteria and/or Petersen criteria were included. Major adverse cardiovascular events (MACE) were defined as a combination of heart failure (HF) hospitalization and all‐cause mortality. Results: A total of 200 patients from four hospitals were included. The mean age at diagnosis was 48.2 years, and 61.5% of the patients were male. Left ventricular ejection fraction (LVEF) < 50% was present in 54% of the patients. Over a mean retrospective time period of 22.2 months, 47 (23.5%) patients experienced MACE. Age (hazard ratio [HR] 1.03; 95% confidence interval [CI] 1.01–1.06; p =.004), LVEF < 50% (HR 2.32; 95% CI 1.09–4.91; p =.028) and ventricular tachycardia/ventricular fibrillation (HR 2.17; 95% CI 1.08–4.37; p =.03) were significantly associated with the risk of MACE. The most common subtype was dilated LVNC (51.3%), followed by benign LVNC (21.3%) and LVNC with arrhythmias (10.5%). Patients with dilated LVNC had significantly increased cumulative incidence of MACE, HF hospitalization, and all‐cause mortality (p <.05). Conclusions: Age, LVEF < 50%, and ventricular tachycardia/ventricular fibrillation were independent risk factors for prognosis of LVNC. The most common subtype was dilated LVNC, which had a worse prognosis. [ABSTRACT FROM AUTHOR]

Excessive trabeculation, often referred to as "noncompacted" myocardium, has been described at all ages, from the fetus to the adult. Current evidence for myocardial development, however, does not support the formation of compact myocardium from noncompacted myocardium, nor the arrest of this process to result in so-called noncompaction. Excessive trabeculation is frequently observed by imaging studies in healthy individuals, as well as in association with pregnancy, athletic activity, and with cardiac diseases of inherited, acquired, developmental, or congenital origins. Adults with incidentally noted excessive trabeculation frequently require no further follow-up based on trabecular pattern alone. Patients with cardiomyopathy and excessive trabeculation are managed by cardiovascular symptoms rather than the trabecular pattern. To date, the prognostic role of excessive trabeculation in adults has not been shown to be independent of other myocardial disease. In neonates and children with excessive trabeculation and normal or abnormal function, clinical caution seems warranted because of the reported association with genetic and neuromuscular disorders. This report summarizes the evidence concerning the etiology, pathophysiology, and clinical relevance of excessive trabeculation. Gaps in current knowledge of the clinical relevance of excessive trabeculation are indicated, with priorities suggested for future research and improved diagnosis in adults and children. [Display omitted] • Current evidence shows that the extent of trabeculated vs compact myocardium in the adult is determined by differential (allometric) growth of each myocardial layer. Because trabeculated myocardium does not coalesce to form the compact myocardial wall, the term "left ventricular noncompaction" is inaccurate and use should be discouraged. • Excessive trabeculation, as diagnosed using existing criteria, may be present as a normal variant or as a response to preload conditions. • In adults incidentally found to have excessive trabeculation with normal myocardial function and morphology, clinical management is determined by other cardiovascular symptoms or abnormalities, without regard to trabecular pattern. • In adults diagnosed with hypertrophic or dilated cardiomyopathy where excessive trabeculation is also present, the extent of ventricular trabeculation has not been demonstrated to alter management nor prognosis. Following guidelines developed specifically for those conditions is recommended. • In infants and children, caution is warranted because fewer data are available regarding the etiology and prognosis of excessive trabeculation. Clinical evaluation for occult neuromuscular disease or another genetic/metabolic etiology may be appropriate. [ABSTRACT FROM AUTHOR]

Abstract Barth syndrome (BTHS) is an X‐linked disorder characterized by cardiomyopathy, skeletal myopathy, and 3‐methylglutaconic aciduria. The causative pathogenic variants for BTHS are in TAZ, which encodes a putative acyltransferase named tafazzin and is involved in the remodeling of cardiolipin in the inner mitochondrial membranes. Pathogenic variants in TAZ result in mitochondrial structural and functional abnormalities. We report a case of infantile BTHS with severe heart failure, left ventricular noncompaction, and lactic acidosis, having a missense c.640C>T (p.His214Tyr) variant in TAZ, which is considered a pathogenic variant based on the previously reported amino acid substitution at the same site (c.641A>G, p.His214Arg). However, in this previously reported case, heart function was compensated and not entirely similar to the present case. Silico prediction analysis suggested that c.640C>T could alter the TAZ messenger RNA (mRNA) splicing process. TAZ mRNAs in isolated peripheral mononuclear cells from the patient and in vitro splicing analysis using minigenes of TAZ found an 8 bp deletion at the 3′ end of exon 8, which resulted in the formation of a termination codon in the coding region of exon 9 (H214Nfs*3). These findings suggest that splicing abnormalities should always be considered in BTHS.

BackgroundLeft ventricular noncompaction (LVNC) is a rare inherited cardiomyopathy with a broad phenotypic spectrum. The genotype-phenotype correlations in fetal-onset LVNC have not yet been fully elucidated. In this report, we present the first case of severe fetal-onset LVNC caused by maternal low-frequency somatic mosaicism of the novel myosin heavy chain 7 (MYH7) mutation.Case presentationA 35-year-old pregnant Japanese woman, gravida 4, para 2, with no significant medical or family history of genetic disorders, presented to our hospital. In her previous pregnancy at 33 years of age, she delivered a male neonate at 30 weeks of gestation with cardiogenic hydrops fetalis. Fetal echocardiography confirmed LVNC prenatally. The neonate died shortly after birth. In the current pregnancy, she again delivered a male neonate with cardiogenic hydrops fetalis caused by LVNC at 32 weeks of gestation. The neonate died shortly after birth. Genetic screening of cardiac disorder-related genes by next-generation sequencing (NGS) was performed which revealed a novel heterozygous missense MYH7 variant, NM_000257.3: c.2729A > T, p.Lys910Ile. After targeted and deep sequencing by NGS, the same MYH7 variant (NM_000257.3: c.2729A > T, p.Lys910Ile) was detected in 6% of the variant allele fraction in the maternal sequence but not in the paternal sequence. The MYH7 variant was not detected by conventional direct sequencing (Sanger sequencing) in either parent.ConclusionsThis case demonstrates that maternal low-frequency somatic mosaicism of an MYH7 mutation can cause fetal-onset severe LVNC in the offspring. To differentiate hereditary MYH7 mutations from de novo MYH7 mutations, parental targeted and deep sequencing by NGS should be considered in addition to Sanger sequencing.

We report the case of an 8-year-old boy with left ventricular noncompaction cardiomyopathy (LVNC) and QT prolongation who experienced further prolongation of the QTc during general anesthesia for extraction of a maxillary mesiodens. Pronounced prolongation of the QTc was observed after induction of general anesthesia with thiamylal and during emergence. No notable fluctuations in blood pressure, heart rate, and estimated continuous cardiac output were observed. We considered it likely that the QT prolongation was triggered by thiamylal and increased sympathetic nervous system activity. During general anesthesia for children with LVNC and QT prolongation, it is necessary to monitor intraoperative hemodynamic fluctuations and prepare for the possible occurrence of arrhythmias. [ABSTRACT FROM AUTHOR]

Objective To screen the pathogenic genes in the patients with left ventricular noncompaction (LVNC) and validate their functions in order to provide references for pathogenesis, genetic counseling and early intervention of the disease. Methods Blood samples from 3 LVNC families attending the outpatient clinic of our hospital from January 2018 to December 2020 were collected for whole-exome sequencing (WES) to obtain the possible pathogenic genes screened in all 3 families. Induced pluripotent stem cells-cardiomyocytes (IPSCs-CMs) were derived and constructed separately from LVNC patients and normal individuals. The cells were collected at different time points and validated by quantitative real-time PCR (qPCR) to observe the expression profiles of above obtained genes during induction and differentiation. Results WES screened 14 possible pathogenic genes commonly expressed in the 3 LVNC families. qPCR results suggested that the expression of these genes changed dynamically at different time points (0, 10, 20 and 30 d), and their expression differed significantly from the normal and LVNC patient groups. Conclusion There were 14 common possible pathogenic genes screened by WES in the 3 LVNC families, and they are involved in affecting cytoskeleton, cell polarity, calcium and potassium ion regulation and energy metabolism.

Arrhythmogenic cardiomyopathy (ACM) is a group of arrhythmogenic disorders of the myocardium that are not caused by ischemic, hypertensive, or valvular heart disease. The clinical manifestations of ACMs may overlap those of dilated cardiomyopathy, complicating the differential diagnosis. In several ACMs, ventricular tachycardia (VT) has been observed at an early stage, regardless of the severity of the disease. Therefore, preventing recurrences of VT can be a clinical challenge. There is a wide range of efficacy and side effects associated with the use of antiarrhythmic drugs (AADs) in the treatment of VT. In addition to AADs, patients with ACM and ventricular tachyarrhythmias may benefit from catheter ablation, especially if they are drug-refractory. The differences in pathogenesis between the various types of ACMs can lead to heterogeneous distributions of arrhythmogenic substrates, non-uniform ablation strategies, and distinct ablation outcomes. Ablation has been documented to be effective in eliminating ventricular tachyarrhythmias in arrhythmogenic right ventricular dysplasia (ARVC), sarcoidosis, Chagas cardiomyopathy, and Brugada syndrome (BrS). As an entity that is rare in nature, ablation for ventricular tachycardia in certain forms of ACM may only be reported through case reports, such as amyloidosis and left ventricular noncompaction. Several types of ACMs, including ARVC, sarcoidosis, Chagas cardiomyopathy, BrS, and left ventricular noncompaction, may exhibit diseased substrates within or adjacent to the epicardium that may be accountable for ventricular arrhythmogenesis. As a result, combining endocardial and epicardial ablation is of clinical importance for successful ablation. The purpose of this article is to provide a comprehensive overview of the substrate characteristics, ablation strategies, and ablation outcomes of various types of ACMs using endocardial and epicardial approaches. [ABSTRACT FROM AUTHOR]

Background: Cardiac magnetic resonance (CMR) has been used to diagnose and risk-stratify patients with left ventricular noncompaction (LVNC). The prognostic value of CMR parameters for LVNC, especially feature tracking (CMR-FT), is not well known in LVNC patients with left ventricular dysfunction. The present study aimed to investigate whether the combination of CMR-FT with traditional CMR parameters can increase the prognostic value of CMR for LVNC patients with reduced left ventricular ejection fraction (LVEF). Methods: A total of 123 candidates were retrospectively included in this multicenter study and 55 LVNC patients (mean age, 45.7 ± 16.2 years; 61.8% men) remained after applying the exclusion criteria. Clinical features, left ventricular (LV) function parameters, global and segment myocardial strain, and late gadolinium enhancement (LGE) were evaluated. The outcomes include the composite events of cardiovascular death, heart transplantation, hospitalization for heart failure, thromboembolic events, and ventricular arrhythmias. Results: After a median follow-up of 5.17 years (interquartile range: 0.17 to 10.58 years), 24 (36.8%) patients experienced at least one major adverse cardiovascular event (MACE). The myocardial strain parameters of patients with events were lower than those of patients without events. In the univariable Cox analysis, LVEF, the presence of LGE, global longitudinal strain (GLS) and segmental strains, including longitudinal strain at the apical level and radial and circumferential strain at the basal level, were significantly associated with MACEs. In the multivariate analysis, LGE (hazard ratio (HR) 3.452, 95% CI 1.133 to 10.518, p = 0.029) was a strong predictor of MACEs and significantly improved the predictive value (chi-square of the model after adding LGE: 7.51 vs. 13.47, p = 0.009). However, myocardial strain parameters were not statistically significant for the prediction of MACEs after adjusting for age, body mass index, LVEF and the presence of LGE and did not increase the prognostic value (chi-square of the model after adding GLS: 13.47 vs. 14.14, p = 0.411) in the multivariate model. Conclusions: The combination of CMR-FT with traditional CMR parameters may not increase the prognostic value of CMR in LVNC patients with reduced LVEF, while the presence of LGE was a strong independent predictor of MACEs and significantly improved the predictive value. [ABSTRACT FROM AUTHOR]

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Abstract Background Left ventricular noncompaction (LVNC) is a rare type of cardiomyopathy, and one of its clinical manifestations is arrhythmia. Cardiovascular magnetic resonance (CMR) is valuable for the diagnosis and prognosis of LVNC. However, studies are lacking on the use of CMR for LVNC patients with arrhythmia. This study aimed to characterize and compare CMR features and prognosis in LVNC patients with and without arrhythmia. Methods Eighty-four LVNC patients diagnosed by CMR were enrolled retrospectively in this study. Clinical data, arrhythmia characteristics, and CMR parameters were collected. Patients were divided into different groups according to the arrhythmia characteristics and CMR manifestations for statistical analysis and comparison. Ventricular tachycardia (VT), ventricular fibrillation (Vf), ventricular flutter (VFL), III° atrioventricular block (III° AVB), Wolff–Parkinson–White syndrome (WPW) and ventricular escape (VE) were defined as malignant arrhythmias and benign arrhythmias included premature ventricular contraction, atrial premature beats, atrial fibrillation, supraventricular tachycardia, supraventricular premature beat, bundle branch block, atrial flutter and sinus tachycardia. The outcome events were defined as a composition event of cardiac death, rehospitalization for heart failure, heart transplantation, and implantation of an implantable cardioverter defibrillator (ICD). Results Sixty-seven LVNC patients (79.76%) mainly presented with arrhythmia, including premature ventricular beat (33 patients [27.73%]), bundle branch block (14 patients [11.77%]), electrocardiogram waveform changes (18 patients [15.13%]), and ventricular tachycardia (11 patients [9.24%]). The cardiac function and structure parameters had no significant difference among the nonarrhythmia group, benign arrhythmia group, and malignant arrhythmia group. However, the presence of late gadolinium enhancement (LGE) was higher in the malignant arrhythmia group than in the other two groups (p = 0.023). At a mean follow-up of 46 months, cardiac events occurred in twenty-three patients (46.94%). Kaplan–Meier analysis showed that there was no statistically significant difference in prognosis among the nonarrhythmia, benign, and malignant arrhythmia groups, but the patients with arrhythmia and association with LGE + or left ventricular ejection fraction (LVEF) 30% (LGE +, HR = 4.035, 95% CI 1.475–11.035; LVEF

We report a unique association of rheumatic heart disease with left ventricular (LV) noncompaction cardiomyopathy in an octogenarian. He had severe mitral stenosis with severe LV systolic dysfunction secondary to noncompaction. Although the association of rheumatic heart disease with LV, noncompaction cardiomyopathy has been described sparsely in the literature, our case is a unique illustration of the presence of LV noncompaction cardiomyopathy contributing toward severe LV systolic dysfunction in rheumatic mitral stenosis in an octogenarian with no coronary artery disease.

Current diagnostic criteria for left ventricular noncompaction (LVNC) may be poorly related to adverse prognosis. Late gadolinium enhancement (LGE) is a predictor of major adverse cardiovascular events (MACE), but risk stratification of LGE in patients with LVNC remains unclear. We retrospectively analyzed the clinical and cardiovascular magnetic resonance (CMR) data of 75 patients from three institutes and examined the correlation between different LGE types and MACE based on the extent, pattern (including a specific ring-like pattern), and locations of LGE in LVNC. A total of 51 patients (68%) presented LGE. A specific ring-like pattern was observed in 9 (12%). MACE occurred in 29 (38.7%) at 4.3 years of follow-up (interquartile range: 2.1–5.7 years). The adjusted hazard ratio (HR) for patients with ring-like LGE were 6.10 (95% CI, 1.39–26.75, p < 0.05). Free-wall or mid-wall LGE was associated with an increased risk of MACE after adjustment (HR 2.85, 95% CI, 1.31–6.21; HR 4.35, 95% CI, 1.23–15.37, respectively, p < 0.05). The risk of MACE in LVNC significantly increased when the LGE extent was greater than 7.5% and ring-like, multiple segments, and free-wall LGE were associated with MACE. These results suggest the value of LGE risk stratification in patients with LVNC. [ABSTRACT FROM AUTHOR]

Variants of the MYH7 gene have been associated with a number of primary cardiac conditions, including left ventricular noncompaction cardiomyopathy (LVNC). Most cases of MYH7-related diseases are associated with such variant types as missense substitutions and in-frame indels. Thus, truncating variants in MYH7 (MYH7tv) and associated mechanism of haploinsufficiency are usually considered not pathogenic in these disorders. However, recent large-scale studies demonstrated evidence of the significance of MYH7tv for LVNC and gave rise to an assumption that haploinsufficiency may be the causal mechanism for LVNC. In this article, we present a family with isolated LVNC and a heterozygous splice variant of the MYH7 gene, analyze possible consequences of this variant and conclude that not all variants that are predicted truncating really act through haploinsufficiency. This study can highlight the importance of a precise assessment of MYH7 splicing variants and their participation in the development of LVNC. [ABSTRACT FROM AUTHOR]

Saw-tooth cardiomyopathy (STC), a rare form of left ventricular cardiomyopathy characterized by saw-tooth like myocardial projections extending from the lateral walls towards the ventricular cavity, is a newly discovered cardiomyopathy first described in 2009. Detailed cardiac magnetic resonance can demonstrate multiple dense myocardial protrusions originating from the inferior wall, interventricular septum and lateral ventricular walls, which differ from typical left ventricular noncompaction. STC case reports are increasing since the first discovery. A total of ten cases have been reported. This review focuses on the clinical presentation and imaging features of this disease and analyzes the latest evidence regarding STC. Furthermore, we summarize the clinical evidence from the current decade, which may enhance detection and diagnosis of this disease in the future. [ABSTRACT FROM AUTHOR]

A 54-year-old male with severe aortic regurgitation (AR), aortic root aneurysm, left ventricular hyper-trabeculation/noncompaction (LVHT) and systolic dysfunction with a left ventricular ejection fraction (LVEF) of 52% underwent successful aortic root replacement. Intraoperative video-endoscopy confirmed LVHT. At 3-year follow-up, he remains in an excellent clinical condition and echocardiography shows an improvement of the systolic function, LVHT and LVEF of 66%. Timely surgical correction of severe AR may also lead to improvement of systolic function in a patient with LVHT. [ABSTRACT FROM AUTHOR]

The same variants in sarcomeric genes can lead to different cardiomyopathies within the same family. This gave rise to the concept of a continuum of sarcomeric cardiomyopathies. However, the manifestations and evolution of these cardiomyopathies in pathogenic variant carriers, including members of the same family, remains poorly understood. We present a case of familial sarcomeric cardiomyopathy caused by heterozygous truncating pathogenic variant p.Q1233* in cardiac myosin-binding protein C (MyBPC3) gene. The proband was first diagnosed with restrictive cardiomyopathy combined with left ventricular noncompaction (LVNC) and sarcoidosis at the age of 64. The predominantly restrictive phenotype of cardiomyopathy is considered to be a result of interaction between LVNC and sarcoid myocarditis. His 39-year-old son and 35-year-old daughter have identical non-obstructive asymmetric hypertrophic cardiomyopathy. The risk of sudden cardiac death in the son is high due to myocardial fibrosis, ischemia and nonsustained VT. We assume that both phenotypes in the family may have originally been different or there may have been a gradual transformation of the hypertrophic phenotype into LVNC. Myocarditis is regarded as an important epigenomic modifier of sarcomeric cardiomyopathy. In the proband and his son, cardioverter-defibrillators were implanted, and the proband experienced appropriate shocks due to ventricular tachycardia/fibrillation. The proband was also treated with corticosteroids. His death at the age of 69 years occurred due to acute gastric hemorrhage accompanied by progressive heart failure. This report confirms the concept of the phenotypic continuum of sarcomeric cardiomyopathies and describes possible phenotypic patterns and their transformation over time. [ABSTRACT FROM AUTHOR]

Background: Left ventricular noncompaction cardiomyopathy (LVNC) is a rare cardiac disorder characterised by the presence of a two-layer myocardium with prominent ventricular trabeculation, intertrabecular deep depressions and an increased risk of heart failure, atrial and ventricular arrhythmias and systemic thromboembolic events in affected patients. The heterogeneous molecular aetiology solved in 10%–50% of patients more frequently involves sarcomeric, cytoskeletal or ion channel protein dysfunction—mainly related to causative MYH7, TTN or MYBPC3 variants. The aim of the study was to determine the molecular spectrum of isolated LVNC in a group of children examined in a single paediatric reference centre. Methods: Thirty-one paediatric patients prospectively diagnosed with LVNC by echocardiography and cardiovascular magnetic resonance examination were recruited into the study group. The molecular analysis included next-generation sequencing (gene panel or whole exome) and classic Sanger sequencing. All selected variants with high priority were co-segregated in the available parents. Results: We identified 16 distinct variants in 11 genes in 16 patients (52%), including 10 novel alterations. The most frequent defects in our cohort were found in the genes HCN4 (n = 4), MYH7 (n = 2) and PRDM16 (n = 2). Other likely disease-causing variants were detected in ACTC1, ACTN2, HCCS, LAMA4, MYH6, RBM20, TAFFAZIN and TTN. Patients with established molecular defects more often presented with arrhythmia, thromboembolic events and death, whereas the predominant symptoms in patients with no identified molecular defects were heart failure and the presence of late gadolinium enhancement. Conclusion: This study expands the genetic and clinical spectrum of childhood LVNC. Although the molecular aetiology of LVNC varies widely, the comprehensive testing of a wide panel of cardiomyopathy-related genes helped to identify underlying molecular defects in more than half of the children in the study group. The molecular spectrum in our cohort correlated with the occurrence of arrhythmia, death and a family history of cardiomyopathy. We confirmed that genetic testing is an integral part of the work-up and management LVNC in children. [ABSTRACT FROM AUTHOR]

Background: Left ventricular noncompaction (LVNC) is recognized within the spectrum of adult cardiomyopathies for its unique pathophysiologic features and clinical challenges. This condition exhibits a wide range of clinical manifestations, from asymptomatic states to severe cardiovascular complications, making its diagnosis and management challenging. This study aimed to synthesize current data on the prevalence, diagnostic methods, clinical outcomes, and treatment efficacy of LVNC in adults to address gaps in understanding and management strategies., Methods: A systematic review and meta-analysis of research from 2000 to March 2024 was conducted, focusing on studies involving adults diagnosed with LVNC. This approach aimed to collect data on the prevalence of LVNC, the diagnostic accuracy of different imaging modalities, clinical manifestations, and the impact of different treatment strategies., Results: The study showed a prevalence of LVNC of 0.5%, with cardiovascular magnetic resonance outperforming echocardiography in diagnosis with a detection rate of 1.3%. Mortality and heart transplantation rates were 12% and 7%, respectively. Significant predictors of adverse outcomes included New York Heart Association (NYHA) class III or IV, ventricular tachycardia, and reduced left ventricular ejection fraction (LVEF), guiding a nuanced approach in tailoring therapeutic strategies to optimize patient care and outcomes., Conclusions: This study advances the understanding of LVNC by refining diagnostic criteria and evaluating management strategies, highlighting the superiority of cardiovascular magnetic resonance. It identifies predictors of adverse outcomes and assesses treatment efficacy, urging precision in diagnosis and tailored treatments. Its comprehensive analysis and methodological rigor make it a key resource advocating a multidisciplinary approach to improve patient outcomes in LVNC., Competing Interests: The author declares no conflict of interest to ensure the impartiality of the study., (Copyright 2024, Llerena-Velastegui.)

Background: Left ventricular noncompaction (LVNC) is a genetically determined cardiomyopathy that occurs following a disruption of endomyocardial morphogenesis. The purpose of this study was to identify the clinical characteristics and genetic profile of children with LVNC. Methods: From February 2008 to July 2020, a total of 32 children (median 11.5 years) with LVNC were prospectively enrolled and followed up for a median of 4.02 years. Diagnosis was made based on characteristic features of LVNC in echocardiography and cardiovascular magnetic resonance (CMR). Patients’ clinical symptoms, family history, ECG, Holter ECG, and genetic tests were also evaluated. Results: The most common presenting symptom was heart failure (31% of children). ECG abnormalities were noted in 56% of patients. The most prominent features were ventricular arrhythmias, sinus bradycardia, and paroxysmal third-degree atrioventricular block. Most of the patients (94%) met the criteria for LVNC and CMR confirmed this diagnosis in 82% of cases. The molecular etiology was found in 53% of children. Conclusion: Although heart failure and arrhythmias were very frequent in our study group, thromboembolic events and genetic syndromes were rare. For the accurate and reliable assessment of children with LVNC, it is necessary to get to know their family history and detailed clinical profile.

The differentiation of dilated cardiomyopathy (DCM) and left ventricular noncompaction (LVNC) is a recurring issue during cardiac imaging processes; thus, we aimed to compare the left ventricular (LV) cardiac MRI characteristics of these patients. Thirty-one nonischemic DCM patients, 42 LVNC patients with reduced ejection fraction and 42 healthy controls were included in this retrospective study. LV volumetric, functional and myocardial mass parameters were measured with a threshold-based technique, while global and segmental strain values and rotational patterns were analyzed with feature-tracking strain analysis. Of the LV volumetric and myocardial mass parameters, only the trabeculated and papillary muscle mass (TPMi) values differed significantly between the patient groups and were higher in the LVNC group (DCM vs LVNC: 43.2 ± 8.9 vs 51.6 ± 13.6 g/m2, p < 0.002). The global longitudinal and circumferential strains were similar between the patient groups and significantly worse than those of the controls. In comparing the segmental strains between the patient groups, only the circumferential apical strain was significantly lower in the LVNC group (DCM vs LVNC: −30.5 ± 13.5 vs −24.5 ± 12.0%, p < 0.05). There was no difference in the rotational pattern between the patient groups, and both healthy and patient populations showed heterogeneous rotational patterns. Despite the similarities between DCM and LVNC in volumetric, global strain parameters, and rotational patterns, we found some differences between the patient groups, as the TPMi was higher and the apical circumferential strains were significantly lower in LVNC. These minor alterations might be due to the morphological characteristics of LVNC with a trabeculated apical region. • Uniquely, we provided data in the comparison of LVNC and DCM using the MassK algorithm. • Global strain parameters did not s how significant differences between patient groups. • Apical segmental circumferential strain values were significantly lower in LVNC. • There was no difference in the rotational pattern between the patient groups. • The alterations might be due to the trabeculated apical region of LVNC. [ABSTRACT FROM AUTHOR]

Left ventricular non-compaction (LVNC) describes the phenotypical phenomena characterized by the presence of excessive trabeculation of the left ventricle which forms a deep recess filled with blood. Considering the lack of a uniform definition of LVNC as well as the "golden standard" it is difficult to estimate the actual incidence of the disease, however, seems to be overdiagnosed, due to unspecific diagnostic criteria. The non-compacted myocardium may appear both as a disease representation or variant of the norm or as an adaptive phenomenon. This article covers different approaches to incidence, pathogenesis, diagnostics, and treatment of LVNC as well as recommendations for patients during follow-up. [ABSTRACT FROM AUTHOR]

Routine vigorous exercise can lead to electrical, structural, and functional adaptations that can enhance exercise performance. There are several factors that determine the type and magnitude of exercise-induced cardiac remodeling (EICR) in trained athletes. In some athletes with pronounced cardiac remodeling, there can be an overlap in morphologic features with mild forms of cardiomyopathy creating gray zone scenarios whereby distinguishing health from disease can be difficult. An integrated clinical approach that factors athlete-specific characteristics (sex, size, sport, ethnicity, and training history) and findings from multimodality imaging are essential to help make this distinction. [ABSTRACT FROM AUTHOR]

The NKX2-5 gene encodes a transcription factor and is actively involved in heart formation and development. A pediatric case with its variant and left ventricular noncompaction (LVNC) has not been reported. A 12-year-old girl with a history of a surgery for atrial septal detect was referred because of syncope during exercise. The electrocardiogram showed atrioventricular block, and the echocardiogram revealed prominent trabeculations in the left ventricular wall, suggesting LVNC. A novel heterozygous variant in the NKX2-5 gene (NM_004387.1: c.255_256delCT, p.Phe86fs) was identified. NKX2-5 variants should be considered in cases with LVNC, congenital heart disease, arrhythmia, and syncope to prevent sudden cardiac death. [ABSTRACT FROM AUTHOR]

Abstract Background Cardiovascular magnetic resonance (CMR) derived fractal analysis of the left ventricle (LV) has been shown in adults to be a useful quantitative measure of trabeculation with high reproducibility and accuracy for the diagnosis of LV non-compaction (LVNC). The aim of this study was to investigate the utility and feasibility of fractal analysis in children. Methods Eighty-four subjects underwent CMR: (1) 28 patients with LVNC (as defined by the Petersen criteria with NC/C ratio $$\ge$$ ≥ 2.3); (2) 28 patients referred by clinicians for assessment of hyper-trabeculation and found not to qualify as LVNC (NC/C $$\ge$$ ≥ 1.8 and

Abstract Background Left ventricular noncompaction is a rare cardiomyopathy characterized by a thin, compacted epicardial layer and a noncompacted endocardial layer, with trabeculations and recesses that communicate with the left ventricular cavity. In the advanced stage of the disease, the classical triad of heart failure, ventricular arrhythmia, and systemic embolization is common. Segments involved are the apex and mid inferior and lateral walls. The right ventricular apex may be affected as well. Case presentation A 29-year-old Caucasian male was hospitalized with dyspnea and fatigue at minimal exertion during the last months before admission. He also described a history of edema of the legs and abdominal pain in the last weeks. Physical examination revealed dyspnea, pulmonary rales, cardiomegaly, hepatomegaly, and splenomegaly. Electrocardiography showed sinus rhythm with nonspecific repolarization changes. Twenty-four-hour Holter monitoring identified ventricular tachycardia episodes with right bundle branch block morphology. Transthoracic echocardiography at admission revealed dilated left ventricle with trabeculations located predominantly at the apex but also in the apical and mid portion of lateral and inferior wall; end-systolic ratio of noncompacted to compacted layers > 2; moderate mitral regurgitation; and reduced left ventricular ejection fraction. Between apical trabeculations, multiple thrombi were found. The right ventricle had normal morphology and function. Speckle-tracking echocardiography also revealed systolic left ventricle dysfunction and solid body rotation. Abdominal echocardiography showed hepatomegaly and splenomegaly. Abdominal computed tomography was suggestive for hepatic and renal infarctions. Laboratory tests revealed high levels of N-terminal pro-brain natriuretic peptide and liver enzymes. Cardiac magnetic resonance evaluation at 1 month after discharge confirmed the diagnosis. The patient received anticoagulants, antiarrhythmics, and heart failure treatment. After 2 months, before device implantation, he presented clinical improvement, and echocardiographic evaluation did not detect thrombi in the left ventricle. Coronary angiography was within normal range. A cardioverter defibrillator was implanted for prevention of sudden cardiac death. Conclusions Left ventricular noncompaction is rare cardiomyopathy, but it should always be considered as a possible diagnosis in a patient hospitalized with heart failure, ventricular arrhythmias, and systemic embolic events. Echocardiography and cardiac magnetic resonance are essential imaging tools for diagnosis and follow-up.

Objective To investigate the changes and mechanism of the cytoskeleton and polarity in cardiomyocyte-like cells derived from patients with left ventricular noncompaction (LVNC). Methods After induced pluripotent stem cells (iPSCs) were isolated from LVNC patients and normal individuals, respectively, the obtained cells were induced to differentiate into cardiomyocyte-like cells. Then transcriptome sequencing was performed. Transmission electron microscopy (TEM) was employed to observe the changes of the myocardial cytoskeleton. Immunofluorescence assay was used to detect the location and expression of cytoskeleton-associated proteins, fibrous actin (F-actin), tubulin dimer (ɑ/β-tublin), and polar protein Par6 and vinculin. Western blotting was used to detect the expression of Rho/Rock pathway key protein, Ras homolog gene family member A (RhoA). Results Both the obtained iPSCs derived from LVNC patients and normal persons positively expressed the surface molecular markers of embryonic stem cells, Oct4, Sox2, SSEA4, and TRA1-81, and could be induced into cardiomyocyte-like clusters with autonomous pulsating rhythm. Immunofluorescence assay indicated that the cardiomyocyte-like cells expressed the surface markers of cardiomyocytes, cTnT and ɑ-actinin. The results of transcriptome sequencing showed that there were multiple differential genes related closely to microtubules between the 2 kinds of cardiomyocyte-like cells. Compared with the cells derived from the normal individuals, there was a disordered arrangement of the cytoskeleton with TEM, significantly decreased expression levels of ɑ/β-tublin (n=62, 226.4±65.1, P < 0.01, Z=-3.451), F-actin (n=62, (236.4±33.2), P < 0.001), and vinculin (n=57, 137.2±35.9), P < 0.001, Z=-3.852). and it was unevenly distributed and obviously concentrated in the cell membrane, and obviously up-regulation of Par6 (n=64, -132.7±43.5, P < 0.01, Z=-3.148) with the aid of immunofluorescence assay. Western blotting demonstrated that the expression of RhoA was significantly increased in the cells derived from the patient group (P < 0.01). Conclusion The cytoskeleton and polarity of cardiomyocyte-like cells derived from LVNC patients are indeed abnormal.

Aorto-ventricular tunnels are rare, congenital extracardiac connections arising from the tubular ascending aorta, above the sinotubular junction, which communicate directly with the ventricular cavity. We present long-term follow-up in a series of five adults undergoing pediatric repair and describe the cardiovascular features and outcomes. Significant aortic regurgitation, ascending aortic aneurysm and left ventricular noncompaction were found to be highly prevalent, emphasizing the need for ongoing surveillance following repair of this anomaly.