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![Non-compaction trait vs. non-compaction cardiomyopathy. The physiological compaction process of the myocardium takes place in embryonic weeks 5–8. In case of disturbed myocardial compaction or excessive intrinsic proliferation, a non-compaction with hypertrabeculation results. During physiological adaptation (P), e.g., in competitive athletes, a non-compaction phenotype can arise de-novo and is not necessarily associated with worse prognosis. However, failing of the structurally altered myocardium can be observed in some cases (F). Heart failure, arrhythmia, and embolism are more frequently observed in the failing state (here called ‘cardiomyopathy’ instead of ‘trait’). Pre-existing cardiac diseases (e.g., dilated cardiomyopathy, aortic regurgitation, ischemic heart disease) can result in secondary maladaptive non-compaction patterns (M). Positive family history for cardiomyopathies or sudden cardiac death, abnormal exercise test, syncope, symptoms of heart failure, elevated cardiac biomarkers, abnormal ECG or arrhythmia, and recurrent systemic embolisms are some hints for pathological state. RA right atrium, LA left atrium, RV right ventricle, LV left ventricle, c dorsal endocardial cushion.
Inspired by Oechslin et al. [55]](publication/332385263/figure/fig5/AS:960105646407680@1605918432008/Non-compaction-trait-vs-non-compaction-cardiomyopathy-The-physiological-compaction.png)
Non-compaction trait vs. non-compaction cardiomyopathy. The physiological compaction process of the myocardium takes place in embryonic weeks 5–8. In case of disturbed myocardial compaction or excessive intrinsic proliferation, a non-compaction with hypertrabeculation results. During physiological adaptation (P), e.g., in competitive athletes, a non-compaction phenotype can arise de-novo and is not necessarily associated with worse prognosis. However, failing of the structurally altered myocardium can be observed in some cases (F). Heart failure, arrhythmia, and embolism are more frequently observed in the failing state (here called ‘cardiomyopathy’ instead of ‘trait’). Pre-existing cardiac diseases (e.g., dilated cardiomyopathy, aortic regurgitation, ischemic heart disease) can result in secondary maladaptive non-compaction patterns (M). Positive family history for cardiomyopathies or sudden cardiac death, abnormal exercise test, syncope, symptoms of heart failure, elevated cardiac biomarkers, abnormal ECG or arrhythmia, and recurrent systemic embolisms are some hints for pathological state. RA right atrium, LA left atrium, RV right ventricle, LV left ventricle, c dorsal endocardial cushion. Inspired by Oechslin et al. [55]
Source publication
Background
Left ventricular non-compaction has been increasingly diagnosed in recent years. However, it is still debated whether non-compaction is a pathological condition or a physiological trait. In this meta-analysis and systematic review, we compare studies, which investigated these two different perspectives. Furthermore, we provide a comprehe...
Citations
... All the surviving patients had developmental delays and 20 patients showed intellectual disability. Twenty patients had large head ratios and 17 had congenital structural and functional abnormalities of the heart, with 16 showing myocardial trabeculae,8 having ventricular septal defects,6 having atrial septal defects, and 4 having patent ductus arteriosus. The remaining abnormalities were Ebstein anomaly, dilated cardiomyopathy, and abnormalities of the aortic arch. ...
... Nearly half of the patients showed prenatal abnormalities (11/23), with five cases of left Ventricular Non-Compaction (LVNC)in the prenatal period [6] and five cases in which this occurred in the neonatal period [4,5]. The incidence of cardiomyopathy in LVNC patients caused by NONO pathogenic variants is significantly higher than the incidence in overall LVNC patients, indicating that LVNC is an early diagnostic clue for the presence of MRXS34 [15,16]. NONO pathogenic variants may make males more susceptible to LVNC and CHD. ...
X-linked intellectual developmental disorder is a rare X-linked genetic disease, manifested as heart disease, intellectual impairment, and developmental disorders.
We report a male infant who presented with dyspnea after birth. Physical examination on admission revealed poor responsiveness, deep eye sockets, a small mandible, abnormalities of the outer ears, and reduced limb muscle tone. The child was moaning with shortness of breath and a positive three-concave sign without pulmonary rales. The heart sounds were weak with a grade 2/6 diastolic heart murmur. Echocardiography showed an enlarged heart with increased trabeculae in the left ventricular muscle wall. X-linked mental retardation syndrome type 34(MRXS34, OMIM# 300967) was diagnosed after exome sequencing showed a c.1131G > A hemizygous variant in the NONO gene. After timely therapy including respiratory support, cardiac glycosides, and diuresis, the child's condition improved and he was discharged at one month of age.
A literature review showed that, to date, 22 live births with X-linked mental retardation have been reported. The NONO-related phenotype can be summarized as a neurological and cardiac developmental disorder, which may be accompanied by multisystem malformations. The present case enriches the knowledge of X-linked intellectual developmental syndromes.
... LVNC is associated with a risk of arrhythmias, thromboembolic events, and heart failure [4,5]. The risk of adverse events is associated with systolic dysfunction, not the extent of the trabeculated myocardium, and is similar for patients with LVNC and dilated cardiomyopathy (DCM) [6][7][8]. ...
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.
... In contrast to our results, where the CMR parameters showed no significant differences among the genetic subgroups, previous investigations described the relationship of pathogenic genotype with LV systolic dysfunction and raised a connection with the extent of trabeculation; however, other studies reported no prognostic impact of trabecular mass (7,11,19,21,(36)(37)(38). Notably, all these studies were conducted on both preserved and reduced LVEF LVNC populations with a high number of HF patients, and to the best of our knowledge, no data were available about these associations in LVNC subjects with preserved LVEF. ...
... Similarly, a recent follow-up study identified LGE as the strongest independent predictor of LVNC-specific complications. Other investigators also described the association between LGE and the P genotype, which is comparable with our results, as we detected LGE only in subjects with CMP-related mutations (11,32,36,37). Interestingly, atypical chest pain was more frequent in subjects without CMP-related mutations, and the prevalence of dizziness and palpitation were comparable among the three genetic subgroups, raising questions regarding their importance in risk stratification. ...
Introduction
The genotype of symptomatic left ventricular noncompaction phenotype (LVNC) subjects with preserved left ventricular ejection fraction (LVEF) and its effect on clinical presentation are less well studied. We aimed to characterize the genetic, cardiac magnetic resonance (CMR) and clinical background, and genotype-phenotype relationship in LVNC with preserved LVEF.
Methods
We included 54 symptomatic LVNC individuals (LVEF: 65 ± 5%) whose samples were analyzed with a 174-gene next-generation sequencing panel and 54 control (C) subjects. The results were evaluated using the criteria of the American College of Medical Genetics and Genomics. Medical data suggesting a higher risk of cardiovascular complications were considered “red flags”.
Results
Of the LVNC population, 24% carried pathogenic or likely pathogenic (P) mutations; 56% carried variants of uncertain significance (VUS); and 20% were free from cardiomyopathy-related mutations. Regarding the CMR parameters, the LVNC and C groups differed significantly, while the three genetic subgroups were comparable. We found a significant relationship between red flags and genotype; furthermore, the number of red flags in a single subject differed significantly among the genetic subgroups (p = 0.002) and correlated with the genotype (r = 0.457, p = 0.01). In 6 out of 7 LVNC subjects diagnosed in childhood, P or VUS mutations were found.
Discussion
The large number of P mutations and the association between red flags and genotype underline the importance of genetic-assisted risk stratification in symptomatic LVNC with preserved LVEF.
... Одним из редких фенотипов НМЛЖ является сочетание с врожденными пороками сердца (ВПС) [4]. По данным метаанализа Kayvanpour E, et al. (2019), ВПС, в т.ч. дефект межпредсердной перегородки (ДМПП), выявляются у 7% пациентов с НМЛЖ [5]. ...
... По данным метаанализа Kayvanpour E, et al. (2019), ВПС, в т.ч. дефект межпредсердной перегородки (ДМПП), выявляются у 7% пациентов с НМЛЖ [5]. Представленный случай демонстрирует трудности подбора антиаритмической терапии у пациентки с НМЛЖ и ДМПП, осложнившимися нарушениями ритма на фоне хронической сердечной недостаточности (ХСН). ...
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.
... Cardiac disease is a continuing source of concern due to its high mortality rate and 'silent' appearance. Left ventricular noncompaction (LVNC) is a disorder that has only recently gained prominence [1]. High-intensity exercise and pregnancy appear to be risk factors for LVNC, and autosomal mutations are also suspected. ...
... High-intensity exercise and pregnancy appear to be risk factors for LVNC, and autosomal mutations are also suspected. It is debatable whether LVNC should be categorised as pathological or physiological [1]. This uncertainty reflects a lack of understanding of the condition and, as a result, complicates the management of LNVC patients [2]. ...
The gold standard for diagnosing left ventricular noncompaction evaluated in this article was compared using cardiac magnetic resonance imaging and echocardiography. To generate results, the paper used systematic data analysis techniques such as article screening, data extraction, meta-analysis, and forest plots. Use data gaps exhibited on forest plots to eliminate untrustworthy data, shown here as major gaps with other data, that should be avoided in follow-up investigations. The value of the aforementioned gold standard for diagnosis is as follows. It was discovered that two figures demonstrated the reliability of cMRI, while the other demonstrated that the echocardiograph was more accurate. Two numbers were eliminated because there was no statistically significant difference, and the data p > 0.05. More data integration is still required.
... 15 Classically, NCM is represented by the triad of heart failure, arrhythmias, and thromboembolic events. 25 A meta-analysis showed that heart failure is present in 43% of cases 26 and may occur due to systolic or diastolic dysfunction even with a pattern of restriction. 27 In the same meta-analysis, 20% of patients had sustained or nonsustained ventricular arrhythmias, mostly monomorphic, and 9% had thromboembolic events. ...
... 27 In the same meta-analysis, 20% of patients had sustained or nonsustained ventricular arrhythmias, mostly monomorphic, and 9% had thromboembolic events. 26 Trabeculations are involved in developing the His-Purkinje system; therefore, any change in this system can cause conduction disorders and arrhythmias. 5 ...
... Similarly, Arbustini has divided LVNC into seven independent subtypes according to etiology and clinical characteristics [109]: (1) idiopathic LVNC, similar to Towbin type 1, with unclear genetics and normal LV morphology and function [121]; (2) LVNC with LV division and dysfunction, such as Barth syndrome and Tafazzinopathies; (3) LVNC with overlapping HCM, DCM, RCM, and ARVC is similar to Towbin 2, 3, 4, and 6. Family history investigation can assist in the differential diagnosis; (4) CHD-related LVNC, similar to Towbin 8; (5) LVNC syndrome is related to single-gene defect and chromosome abnormality, such as Fabry disease; (6) acquired and potentially reversible iLVNC is associated with chronic renal failure, chain red cell disease, athletes, and pregnancy [122][123][124][125]; (7) RV noncompaction, is similar to Towbin 7. Two comprehensive classifications demonstrate high consistency, with LVNC overlapping other cardiomyopathy and CHD, having specific diagnostic and therapeutic significance. The Arbutini classification takes into account acquired LVNC, broadens the etiological spectrum of LVNC classifications, and provides a comprehensive and comprehensive description of accurate clinical LVNC subtypes. ...
... The clinical outcome of TTN and RBM20 mutations is worse. Children with MYBP3 mutations have an increased risk of major adverse cardiac events (HR = 5.20), and children with MYH7 mutations have a lower risk (HR = 0.17) [125,126]. A Chinese cohort study finds that there is a difference in prognosis between nonmutant and non-sarcomere mutant LVNC. ...
... DSG2 mutations occur in HCM, DCM, and ARVC. Homozygous [109,110] LVNC with other cardiomyopathies The prognosis depends on other cardiomyopathies [109,110] Acquired LVNC Associated with chronic renal failure, chain red cell disease, athletes, and pregnancy [123][124][125][126] Genomics Partial sarcomere gene mutations (TTN and MYBP3) ...
Abstractt
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.
... Human genetic studies suggest that LVNC is associated with mutations in a variety of genes, including myosin heavy chain 7 (MYH7), myosin binding protein C3 (MYBPC3), LIM domain binding protein 3 (ZASP), tafazzin (TAZ/G4.5), desmin (DES), and others (12)(13)(14)(15)(16). 20%-40% of LVNC cases tend to be familial, with inheritance as an autosomal dominant or Xlinked recessive disorder. ...
Background
Becker 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 report
In 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.
Conclusion
This 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.
... variants are identified in 12% to 16% of patients with hypertrophic cardiomyopathy (HCM), in 6% to 14% of patients with noncompaction cardiomyopathy (NCCM), and in 2% to 5% of patients with dilated cardiomyopathy (DCM). [3][4][5] Clinical severity is highly variable, with incomplete penetrance. 6 MYH7 variants are frequently identified in pediatric cardiomyopathies. ...
Background:
MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.
Objectives:
This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.
Methods:
In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.
Results:
In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001).
Conclusions:
MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.
... Previous studies have shown that TTN is a common pathogenic gene in dilated cardiomyopathy and hypertrophic cardiomyopathy, and in recent years, the role of TTN in LVNC has received increasing attention. In a meta-analysis published by Elham including 2,271 LVNC patients, TTN was found to be the most common pathogenic gene in LVNC, with a detection rate of 11% [17]. ...
Background
Left ventricular noncompaction (LVNC) is a specific type of cardiomyopathy characterized by coarse trabeculae and interspersed trabecular crypts within the ventricles. Clinical presentation varies widely and may be nonsignificant or may present with progressive heart failure, malignant arrhythmias, and multiorgan embolism. The mode of inheritance is highly heterogeneous but is most commonly autosomal dominant. The TTN gene encodes titin, which is not only an elastic component of muscle contraction but also mediates multiple signalling pathways in striated muscle cells. In recent years, mutations in the TTN gene have been found to be associated with LVNC, but the exact pathogenesis is still not fully clarified.
Case presentation
In this article, we report a case of an adult LVNC patient with a TTN gene variant, c.87857G > A (p. Trp29286*), that has not been reported previously. This 43-year-old adult male was hospitalized repeatedly for heart failure. Echocardiography showed reduced myocardial contractility, dilated left ventricle with many prominent trabeculae, and a loose texture of the left ventricular layer of myocardium with crypt-like changes. During the out-of-hospital follow-up, the patient had no significant signs or symptoms of discomfort.
Conclusion
This case report enriches the mutational spectrum of the TTN gene in LVNC and provides a basis for genetic counselling and treatment of this patient. Clinicians should improve their understanding of LVNC, focusing on exploring its pathogenesis and genetic characteristics to provide new directions for future diagnosis and treatment.
