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Left ventricular noncompaction

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Left ventricular noncompaction. Core disease mechanisms, molecular and cel...

2026-04-21
Asta MONDO:0018901 Model: Asta Scientific Corpus Retrieval 20 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Left ventricular noncompaction. Core disease mechanisms, molecular and cel...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 20
  • Snippets retrieved: 20

Relevant Papers

[1] Advances in symptomatic therapy for left ventricular non-compaction in children

  • Authors: Dong Li, Ce Wang
  • Year: 2023
  • Venue: Frontiers in Pediatrics
  • URL: https://www.semanticscholar.org/paper/4d1e712606624d4faa7a1a3418fc3579b3c81dbd
  • DOI: 10.3389/fped.2023.1147362
  • PMID: 37215603
  • PMCID: 10192632
  • Citations: 6
  • Summary: This review summarized and discussed the coping methods for different left ventricular non-compaction symptoms and suggested strategies to reduce its incidence or severity.
  • Evidence snippets:
  • Snippet 1 (score: 0.615) > hmias are also common complications of high clinical concern in patients with LVNC. In addition, these patients often have a neuromuscular disease and may experience fatigue (17, 18), muscle aches and pains, and elevated creatine kinase levels (19). The relevant data are compiled in Table 1. Moreover, even though several children with LVNC have adverse outcomes, to date, no clinically targeted treatment exists, and only symptomatic or prophylactic treatment is available (20-23). > Generally speaking, left ventricular noncompaction is a congenital disease with unknown etiology (26). At present, there is no literature to prove that adult myocardial noncompaction has an acquired trend or mechanism. Some patients with left ventricular noncompaction are asymptomatic from birth to onset, and it is not discovered until they have heart-related symptoms or physical examination. This is called myocardial noncompaction in adults. Therefore, both adults and children with myocardial noncompaction are congenital diseases, but the time of discovery or symptoms is different (27). > In this review, we discuss current advances in the clinical management of the different symptoms of LVNC to further the search for more effective treatments for the various related complications and facilitate the progress of clinical research. The latest treatment strategy, indications and contraindications are compiled in Figures 1-3. Simultaneously, our review provides potential insight for clinical discoveries in the treatment of LVNC.

[2] Left Ventricular Noncompaction in Advanced Heart Failure With an Anomalous Coronary Artery: A Case Report

  • Authors: Khaleel Quasem, M. Carrasquel, Jordan Felice, Britni Smith, Dania Baraka et al.
  • Year: 2025
  • Venue: Cureus
  • URL: https://www.semanticscholar.org/paper/6c6befe1e221e91d37a630d1fa265d2e09a8513a
  • DOI: 10.7759/cureus.80015
  • PMID: 40182365
  • PMCID: 11966663
  • Summary: The case of a 77-year-old male with chronic atrial fibrillation and nonischemic cardiomyopathy who was found to have severe LVNC is presented, highlighting its potential for late onset, the necessity of multimodality imaging to detect coexisting anomalies, and the importance of a comprehensive treatment approach to optimize outcomes in older adults.
  • Evidence snippets:
  • Snippet 1 (score: 0.545) > Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized by excessive trabeculation of the myocardium, resulting from incomplete compaction of normal myocardial fibers [1]. This process creates a thick, noncompacted endocardial layer over a thinner compacted epicardium. While LVNC was traditionally considered a congenital disorder, emerging evidence suggests it can also be acquired, indicating a multifactorial etiology [2,3]. Myocardial remodeling due to volume overload or progressive changes in other cardiomyopathies has been proposed as a potential mechanism for acquired LVNC. This abnormal myocardial structure can lead to significant ventricular dysfunction, increasing the risk of heart failure, arrhythmias, and thromboembolic events -underscoring the importance of early detection and appropriate management [4]. > LVNC presents along a broad clinical spectrum. Some individuals remain asymptomatic and receive a diagnosis incidentally, while others develop severe cardiac complications [1,2]. In some cases, arrhythmias serve as the initial clinical manifestation, preceding the onset of symptomatic heart failure or thromboembolic complications. These arrhythmias, ranging from atrial fibrillation to potentially lifethreatening ventricular tachyarrhythmias, are thought to arise from structural irregularities that disrupt normal electrical conduction. Diagnosis relies on echocardiography and cardiac MRI [3,5]; however, distinguishing LVNC from other cardiomyopathies, such as dilated or hypertrophic cardiomyopathy with deep trabeculations, remains challenging due to overlapping structural and functional characteristics. Careful imaging interpretation, combined with clinical context, is essential for an accurate diagnosis. > Several factors influence the progression of LVNC to overt heart failure or significant arrhythmias, including the extent of noncompaction, left ventricular systolic dysfunction, underlying comorbidities (e.g., hypertension and coronary artery disease), and early manifestations of arrhythmias.

[3] Expression Signatures of Long Noncoding RNAs in Left Ventricular Noncompaction

  • Authors: Qingshan Tian, Hanxiao Niu, Dingyang Liu, Na Ta, Qing Yang et al.
  • Year: 2021
  • Venue: Frontiers in Cardiovascular Medicine
  • URL: https://www.semanticscholar.org/paper/44e140f89a1fe15317061c115c86df953959be6e
  • DOI: 10.3389/fcvm.2021.763858
  • PMID: 34859074
  • PMCID: 8631435
  • Citations: 1
  • Summary: The use of LncRNA microarray is first reported to understand the pathogenesis of LVNC and to identify several lncRNA and genes and their targets as potential biomarkers.
  • Evidence snippets:
  • Snippet 1 (score: 0.520) > Left ventricular noncompaction is a rare disease that is characterized by the failure of densification in the normal embryonic cardiac tissue. It can occur in isolation or association with congenital heart defects (CHDs), neuromuscular disorders, and systemic heart anomalies (1,2). Morphological features of left ventricular noncompaction (LVNC) consist of deep trabecular recesses in the myocardial wall with noncompaction of the loosely interwoven meshwork in the left ventricular cavity (3). The typical clinical result is a triad of heart failure, arrhythmias, and systemic embolism (4). > Left ventricular noncompaction is a genetically heterogeneous disease (5) and is associated with genes and/or proteins that are involved in sarcomere (MYH7, ACTC, MYBPC3, TNNT2), cytoskeletal (ZASP, LMNA), and mitochondrial structure or function (TAZ) (6)(7)(8)(9). However, using exome and mitochondrial DNA sequencing from myocardial tissue samples, Liu Z et al. identified mutations in 16S rRNA 2336T>C mitochondrial mutation but did not detect any pathogenic mutations in TNNT2 and MYBPC3 genes (10). > Long noncoding RNA molecules are >200 nt in length, similar to mRNA, but do not code for structural proteins. Rather, they modulate the expression of protein-coding genes (11). Particularly, relating lncRNA with disease pathogenesis has widespread implications. Long noncoding RNAs (LncRNAs) are easily targetable, and their expression can be controlled from external oligo DNA or RNA that can be administered through blood or tissue specifically (12). A disease development could be delayed or cured by externally manipulating their expressions. Such advantages recently gained specific interest in identifying disease-specific lncRNA (13,14). > Numerous studies show that lncRNAs play a positive and negative role in the differentiation, development, and progression of many diseases such as cancer, neurodegenerative diseases, and heart diseases (13,(15)(16)(17).

[4] Bifid cardiac apex and spongiform cardiomyopathy in fetus with small microdeletion 16p12.2 of paternal origin. Critical points in family communication on 16p12.2 microdeletion

  • Authors: M. Stabile, Anna F. Rispoli, Maurizio Capuozzo, Umberto Ferbo, G. Stabile
  • Year: 2023
  • Venue: Clinical Case Reports
  • URL: https://www.semanticscholar.org/paper/6a73ad388d154050c68af25faa2ae4ca9d1b7aa4
  • DOI: 10.1002/ccr3.7602
  • PMID: 37405046
  • PMCID: 10315447
  • Citations: 3
  • Summary: This is the first case of fetal 16p12.2 microdeletion syndrome inherited from a normal father with autopsy description and evidence of spongious cardiomyopathy and first trimester intake of doxycycline could be a cofactor.
  • Evidence snippets:
  • Snippet 1 (score: 0.503) > The UQCRC2 (ubiQuinol-cytochrome c reductase core protein II) gene encodes a subunit of mitochondrial complex III; the homozygous mutations of the gene can give neonatal acidosis with hyperammonemia and hypoglycemia. It is to be considered that the mutations could have a milder effect than the deletion involving complete loss of the gene. > Maternal thrombophilia and the intake of doxycycline during pregnancy may have contributed to the pathological phenotype of the fetus. Doxycycline falls into category D (positive evidence of human fetal risk) according to the US FDA pregnancy category. > Generally, patients with 16p12.2 microdeletion have congenital heart disease (CHD), hypoplastic left heart syndrome (HLHS), and bicuspid aortic valve (BAV). 8 From the literature review, our case with the 16p12.2 microdeletion is the only one documented by autopsy with this particular cardiac phenotype associated with left ventricular noncompaction (LVNC). Left ventricular noncompaction (LVNC) is a very rare congenital cardiomyopathy. It is a disease of endomyocardial trabeculations that increase in number and prominence. This cardiomyopathy carries a high risk of malignant arrhythmias, thromboembolic phenomenon, and left ventricular dysfunction. This disease also has other names like spongy myocardium, spongiform cardiomyopathy, hypertrabeculation, persisting myocardial sinusoids, or zaspopathy. 9 The mechanisms underlying noncompaction of the ventricular myocardium are still poorly understood; the small GTPase Rac1, with cytogenetic location on 7p22.1 (OMIM #602048) acts as a crucial regulator of numerous developmental events. Rac1 deficiency in the myocardium impairs cardiomyocyte elongation and organization, and proliferative growth of the heart.

[5] A novel loss-of-function mutation in NRAP is associated with left ventricular non-compaction cardiomyopathy

  • Authors: Zhongman Zhang, Kangkang Xu, Lianfu Ji, Han Zhang, Jie Yin et al.
  • Year: 2023
  • Venue: Frontiers in Cardiovascular Medicine
  • URL: https://www.semanticscholar.org/paper/7aece12fa6728ed05641f00b40606761b3939409
  • DOI: 10.3389/fcvm.2023.1097957
  • PMID: 36815016
  • PMCID: 9940605
  • Citations: 9
  • Summary: RNA-sequencing showed that the expression of genes related to heart development decreased significantly, and the NRAP gene mutation could participate in biological processes (BPs) such as myocardial contraction, cell adhesion, myosin coarse filament assembly of striated muscle, myOSin complex composition, and muscle α-actin binding.
  • Evidence snippets:
  • Snippet 1 (score: 0.499) > Left ventricular non-compaction (LVNC) was first described in 1990 (1) and was known as a unique type of inherited cardiomyopathy characterized by excessive trabecular meshwork and deep intertrabecular recesses in the LV wall (2,3). The prevalence of LVNC in the pediatric age is around 0.14% (4), and individual differences in clinical manifestations are relatively large from being asymptomatic to heart failure. LVNC is a polygenic heterogenic cardiomyopathy inherited as an autosomal dominant or X-linked recessive disorder, although autosomal recessive and mitochondrial (maternal) inheritance also occur (5). The etiology and specific pathogenesis of LVNC have not been fully elucidated. The molecular genetic analysis uncovered causal mutations for LVNC in many genes, including NKX2-5, TAZ, LMNA, MYH7, ACTC1, LDB3, TNNT2, and MYBPC3, which encode mitochondrial proteins, sarcomere proteins, and cytoskeleton (5,6). However, the types of these pathogenic genes and mutations are complex, and there are interactions between various pathogenic genes, which makes the mechanism study quite complicated. > Therefore, for LVNC, the precise pathogenic mechanism from molecular component and cellular component (CC) to clinical phenotype is still unknown. At present, clinical drug treatment cannot reverse the progression of LVNC, and the treatment is mainly symptomatic. It becomes especially important to discover the causative gene of LVNC and clarify the functional mechanism to define genotype-to-phenotype associations and provide a theoretical basis for gene-targeted therapy. > Nebulin-related-anchoring protein (NRAP) is a multi-domain cytoskeletal protein specifically expressed at the terminal bundles of actin filaments at the myotendinous junction of skeletal muscle and the intercalated disk of cardiac muscles (7). It is located on chromosome 10q25.3

[6] Left Ventricular Noncompaction Is Associated with Valvular Regurgitation and a Variety of Arrhythmias

  • Authors: Qing Li, Lianjie Miao, L. Xia, Hala Y. Abdelnasser, Fang Zhang et al.
  • Year: 2022
  • Venue: Journal of Cardiovascular Development and Disease
  • URL: https://www.semanticscholar.org/paper/e8986c13856ab763c43317ef2add51d7b3c3424e
  • DOI: 10.3390/jcdd9020049
  • PMID: 35200702
  • PMCID: 8876824
  • Citations: 10
  • Summary: Evidence is added to support a congenital origin of LVNC that might benefit the diagnosis and subsequent characterization of LV NC patients and reveal some novel findings.
  • Evidence snippets:
  • Snippet 1 (score: 0.497) > Left ventricular noncompaction (LVNC: OMIM No. 604169) is a type of cardiomyopathy anatomically characterized by prominent ventricular trabeculation and deep intertrabecular recesses [1][2][3]. It was reported for the first time in 1969, being addressed as a spongy myocardial condition back then [4]. In the following years, LVNC has gained tremendous attention due to the improvements in cardiac imaging techniques, primarily echocardiography and magnetic resonance imaging, that have enabled more detailed visualization and increased clinical awareness of this syndrome. Subsequently, many LVNC cardiomyopathy cases were reported, and AHA enlisted LVNC as a type of cardiomyopathy in 2006 [3]. LVNC shows highly variable clinical manifestations ranging from asymptomatic to symptomatic, and the major clinical features of LVNC are heart failure, arrhythmias, thromboembolic events, and sudden death [5]. Its symptoms are progressive, considered the 3rd most common cardiomyopathy in the pediatric population, and the mortality of patients with LVNC ranges from 5% to 47% [6][7][8]. Despite its clinical significance, the mechanism of trabecular compaction and the etiology of LVNC are unknown. Moreover, whether LVNC is acquired or congenital cardiomyopathy has been an unraveled controversy [9]. The focus of most clinical investigations on isolated adult LVNC patients failed to trace the anomalies in embryonic developmental stages, and the knowledge gap regarding the molecular level regulation of trabeculation could be the possible reason [10,11]. > As abnormalities in trabecular and ventricular morphogenesis lead to LVNC, the revelation of the biological and physiological development of trabecular formation and ventricular compaction will help elucidate the etiology of LVNC [12,13]. Trabeculae are sheet-like structures extending from the myocardium to the heart lumen and function to increase surface area to support nutrition and oxygen supply when the coronary system is not yet established [14].

[7] Elevated myocardial SORBS2 and the underlying implications in left ventricular noncompaction cardiomyopathy

  • Authors: Chunyan Li, Fan Liu, Shenghua Liu, H. Pan, Haiwei Du et al.
  • Year: 2020
  • Venue: EBioMedicine
  • URL: https://www.semanticscholar.org/paper/de61b3ad5bfa119df19d4d8324bafc2532088bf7
  • DOI: 10.1016/j.ebiom.2020.102695
  • PMID: 32143182
  • PMCID: 7058526
  • Citations: 22
  • Influential citations: 1
  • Summary: A novel mechanism through which SORBS2 interacts with β-tubulin and promotes microtubule densification, eventually effecting JP2 distribution and T-tubule, potentially contributing to heart failure in LVNC disease is identified.
  • Evidence snippets:
  • Snippet 1 (score: 0.493) > Left ventricular noncompaction cardiomyopathy (LVNC) is associated with left ventricular diastolic and systolic dysfunction. The myocardial wall is often thickened with a thin, compacted epicardial layer and a thickened endocardial layer. One of LVNC guidelines is to prevent the progression and development of heart failure [29]. > LVNC has gained increasing attention in recent years [30] because of its association with high rates of mortality and morbidity in adults, including heart failure, arrhythmias, and thromboembolic events [31À33]. LVNC may be due to the arrest of the normal compaction process of the myocardial wall during fetal development [34]. Numerous genetic disorders have been reported to be associated with LVNC, including sarcomere and Z-disk gene mutations [35,36]. Regardless of the complicated heterogenous causes of LVNC [37], heart failure is one of the most common clinical consequences in LVNC patients, but the relationship between LVNC and heart failure is not well understood and requires further study [35,36]. All the 8 LVNC patients waiting for heart transplantation, used in our proteomic analyses, suffered from heart failure with severely reduced LV ejection fraction (EF) of 18%À37%. In this study, our primary intention is focused on the identification of the key signaling pathway whose dysfunction has a causal role in the occurrence of heart failure in LVNC patients, but not on the molecular mechanism of LVNC. > The left ventricle (LV) heart samples used in our study were obtained from heart transplantation patients clinically diagnosed with LVNC on the basis of echocardiographic or CMR documentation, and autopsy findings of explanted hearts, with a distinct two-layered appearance of trabeculated and compacted myocardium. Using comparative proteomic analyses, we identified 45 proteins up-regulated in LVNC hearts but not in HCM and ARVC hearts.

[8] A proposed strategy for anticoagulation therapy in noncompaction cardiomyopathy

  • Authors: C. Chimenti, C. Lavalle, M. Magnocavallo, Maria Alfarano, M. Mariani et al.
  • Year: 2021
  • Venue: ESC Heart Failure
  • URL: https://www.semanticscholar.org/paper/d7411ab6be4bb9de52b8f11583d25ac53b9734c4
  • DOI: 10.1002/ehf2.13694
  • PMID: 34918480
  • PMCID: 8788052
  • Citations: 34
  • Influential citations: 5
  • Summary: The aim of the present study is to review the available literature on NCCM with particular attention on thromboembolic risk stratification and prevention and the current evidence for oral anticoagulation therapy.
  • Evidence snippets:
  • Snippet 1 (score: 0.485) > Noncompaction cardiomyopathy (NCCM) is a rare condition characterized by prominent left ventricular (LV) trabeculae and deep intertrabecular recesses, first described in 1969 by Feldt et al., 1 who reported a biventricular spongy myocardium in a female patient who died at the age of 3 months. NCCM is characterized by a two-layered myocardial structure, characterized by a spongy endocardial layer and a thinner and compacted epicardial one. Apical and lateral segments of the LV are the most commonly involved, but both ventricles can be affected. > The prevalence of NCCM is unknown, but it has been estimated to be approximately 0.05-0.27% among adults referred to echocardiography lab, 2 with males more affected than females. 3 Age at the time of diagnosis is variable from early infancy to late adulthood. 3 Noncompaction cardiomyopathy is a genetic cardiomyopathy, because it has been described in association with mutations in more than 40 genes coding for sarcomeric, cytoskeletal, Z-line, and mitochondrial proteins 4 and even in chromosomal defects. 3 A strong genotype-phenotype correlation has been reported for Hyperpolarization Activated Cyclic Nucleotide gated potassium channel 4 (HCN4), Titin (TTN), and Lamin A/C (LMNA) mutations, with a high incidence of heart failure (HF) and ventricular arrhythmias. 5 Furthermore, NCCM can be associated to genetic syndromes, including congenital heart disease, neuromuscular disorders, and facial dysmorphisms. 5 From a pathogenetic point of view, NCCM may be due to an abnormal myocardial compaction during intrauterine cardiac development. 6 However, some authors have suggested that NCCM could be the result of abnormal persistence of the trabecular layer rather than the effect of noncompaction of the ventricular wall. 6 Clinical presentation of NCCM is highly variable, ranging from no symptoms to end-stage HF, lethal arrhythmias, sudden cardiac death, or thromboembolic events (stroke, transient ischaemic attack, me

[9] Role of Col1a2 and Postn in left ventricular noncompaction cardiomyopathy

  • Authors: Huibing Liu, Ling-bing Meng, Qian Liu
  • Year: 2025
  • Venue: Journal of Cardiothoracic Surgery
  • URL: https://www.semanticscholar.org/paper/2f2a34464fc3d8a4ea7b1120afbaf573846ce247
  • DOI: 10.1186/s13019-025-03509-4
  • PMID: 40618167
  • PMCID: 12229011
  • Citations: 2
  • Summary: Left ventricular noncompaction cardiomyopathy (LVNC) is a rare myocardial developmental anomaly characterized by incomplete myocardial compact layer development in the left ventricular wall, resulting in a multilayered trabeculated myocardium. The datasets GSE71912 and GSE113251 of left ventricular noncompaction cardiomyopathy were downloaded from the gene expression omnibus (GEO) database generated from GPL13912 and GPL11002 platforms. Batch normalization was performed, followed by different...
  • Evidence snippets:
  • Snippet 1 (score: 0.481) > Left ventricular noncompaction cardiomyopathy (LVNC) is a relatively rare type of cardiomyopathy, primarily characterized by incomplete development of the compact layer of the left ventricular myocardium. This results in a thickened noncompacted layer of the ventricular wall, giving the heart a distinct "spongy" appearance with deep trabeculated recesses [1]. LVNC may occur as an isolated condition or in conjunction with other cardiac abnormalities. Its prevalence among cardiomyopathies is relatively low, affecting approximately 1 to 3 adults per 10,000 people [2]. LVNC can develop at any age, including infancy, childhood, and adulthood. The condition is more common in males than females, and in adults, it usually manifests in middle age or later [3]. The clinical presentation and prognosis vary significantly. Some patients may be asymptomatic, while others may develop severe complications such as heart failure, arrhythmias, or sudden cardiac death. Echocardiography and magnetic resonance imaging typically reveal uneven wall thickness in the left ventricle, displaying the characteristic "spongy" structure [4]. > Treatment options for LVNC include medication (such as ACE inhibitors and β-adrenergic blockers), management of arrhythmias, and heart failure treatment. In severe cases, implantable cardioverter defibrillators or heart transplants may be required [5,6]. The etiology of LVNC is unclear, but it is likely associated with genetic factors, chromosomal abnormalities, and gene fusions. Therefore, it is crucial to study the molecular mechanisms underlying LVNC. > In recent years, bioinformatics has made significant advances in life sciences and medicine, becoming a vital tool for understanding complex biological systems, disease mechanisms, and personalized medicine [7]. Bioinformatics excels in its efficiency and comprehensiveness. By integrating various data types, bioinformatics provides a more holistic and systematic view of biological information, enabling researchers to extract valuable knowledge from vast datasets.

[10] Electrocardiographic findings in correlation to magnetic resonance imaging patterns in African patients with isolated ventricular noncompaction

  • Authors: Salwa Akhbour, I. Fellat, Nada Fennich, S. Abdelali, N. Doghmi et al.
  • Year: 2014
  • Venue: Anatolian Journal of Cardiology
  • URL: https://www.semanticscholar.org/paper/2830fcf849c534626293c56be914752e522da369
  • DOI: 10.5152/akd.2014.5577
  • PMID: 25537996
  • PMCID: 5337034
  • Citations: 12
  • Influential citations: 1
  • Summary: While electrocardiographic abnormalities are frequent in isolated ventricular noncompactison, no specific patterns were identified and more large studies are needed for stratification of arrhythmic risk of this highly arrhythmogenic substrate.
  • Evidence snippets:
  • Snippet 1 (score: 0.464) > Mutations in the human cardiac sodium channel alpha-subunit gene (SCN5A), a well-known gene involved in multiple cardiac arrhythmias, were highly associated with arrhythmias in patients with left ventricular noncompaction than in those without them (50% vs. 7%: p=0.0003). The most frequent arrhythmias were VT and premature ventricular beats (20). This report suggests that the mechanism underlying VT in IVNC could be a gene mutation and may explain the lack of correlation between VT and ventricular dysfunction or fibrosis. Accordingly, we need more studies to clarify risk factors for VT in IVNC. > Patients with IVNC may develop supraventricular arrhythmias (4%-29%) (6,8). Supraventricular tachycardia revealed IVNC in 12.5% patients in the present study. In a large series (21), they identified 9 patients with atrial fibrillation among 238 patients affected by noncompaction. No case of supraventricular tachycardia was noted. The authors concluded that the atria are not involved in the noncompaction process when the majority of patients has dilated cardiomyopathy. In our study, supraventricular arrhythmias are not a consequence of atrial dilatation or systolic dysfunction but may be due to cardiac involvement in the context of ventricular noncompaction. > Only one patient in our series presented with WPW syndrome. It is more frequently reported in children (12%-15%) than in adults (0%-2.7%) (3, 6-8, 15, 22, 23). Failed regression of developmental embryologic atrioventricular anatomical and electrical continuity during embryonic development in the noncompacted myocardium can explain this association. In our patient, the accessory pathway was type B. This finding is consistent with other reports, because defects in the annulus fibrosis lead to the formation of accessory pathways on the right side of the heart around the tricuspid valve (24).

[11] The Role of Ventricular Assist Devices in Patients With Heart Failure Due to Dilated Cardiomyopathy: A Systematic Review

  • Authors: Billy McBenedict, W. Hauwanga, Emmanuel S Amadi, Melvin Chun Yang Yau, C. R. Amuzie et al.
  • Year: 2024
  • Venue: Cureus
  • URL: https://www.semanticscholar.org/paper/209c45dbd836722b8376b65f34c4b7ae1187a259
  • DOI: 10.7759/cureus.66259
  • PMID: 39238676
  • PMCID: 11377123
  • Citations: 1
  • Summary: It is concluded that VADs play a crucial role in managing advanced HF due to DCM by providing mechanical circulatory support, improving cardiac function, and enhancing patient survival and quality of life.
  • Evidence snippets:
  • Snippet 1 (score: 0.464) > Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by left ventricular (LV) or biventricular dilation and systolic dysfunction in the absence of either pressure or volume overload or coronary artery disease (CAD) sufficient enough to explain the dysfunction [1]. DCM is marked by the dilation and impaired contraction of the ventricles, primarily affecting the left ventricle and resulting in systolic dysfunction. This condition increases ventricular volumes to maintain cardiac output, leading to the thin-walled, dilated appearance of the left ventricle. Genetic mutations are significant contributors to DCM, impacting various intracellular structures and pathways. Key mechanisms include deficits in force generation due to mutations in sarcomeric proteins like titin and myosin, defects in the nuclear envelope involving Lamin-A/C mutations, and issues with force transmission linked to cytoskeletal protein mutations such as filamins and dystrophin. Additionally, abnormalities in cell-to-cell adhesion from desmosomal protein mutations, mitochondrial energy production defects, calcium-cycling issues from phospholamban gene mutations, ion channel mutations, epigenetic perturbations, and protein misfolding diseases all contribute to the pathophysiology of DCM [1]. > Cardiac remodeling in DCM involves significant alterations in function, particularly in the LV pressurevolume relationship. Increased end-diastolic volumes and pressures, along with diastolic dysfunction due to incomplete relaxation and increased stiffness, complicate the clinical scenario [1]. The law of Laplace explains that wall tension is directly proportional to ventricular dilation and inversely proportional to wall thickness, highlighting the increased afterload and energetic consequences of heart failure (HF) [1]. Understanding these genetic and molecular mechanisms is crucial for developing targeted therapies and improving outcomes for DCM patients [2]. > Histological examination of the myocardium typically shows nonspecific changes of fibrosis and hypertrophy, along with myocardial injury marked by an inflammatory cell infiltrate [2]. It is the most common form of cardiomyopathy and the most frequent indication for cardiac transplantation.

[12] Concise Review: The Current State of Human In Vitro Cardiac Disease Modeling: A Focus on Gene Editing and Tissue Engineering

  • Authors: M. Hoes, N. Bomer, P. van der Meer
  • Year: 2018
  • Venue: Stem Cells Translational Medicine
  • URL: https://www.semanticscholar.org/paper/51dc8ec48dc758584279d54d6072d8fa15f7b8f6
  • DOI: 10.1002/sctm.18-0052
  • PMID: 30302938
  • PMCID: 6312446
  • Citations: 38
  • Summary: Limits in the field of human in vitro cardiomyopathy modeling are emphasized, including residual somatic epigenetic signatures induced pluripotent stem cells, and modeling diseases with unknown genetic causes.
  • Evidence snippets:
  • Snippet 1 (score: 0.454) > A plethora of genetic mutations have been associated with the pathogenesis of genetic heart diseases, including the main inherited cardiomyopathies (i.e., HCM, DCM, ACM, and LVNC). Investigating how genetic mutations explain causality in the pathophysiology of cardiomyopathies and how they interact with secondary genetic and environmental factors is imperative to improving diagnosis and decision-making regarding treatment strategies. The introduction of patient-specific hiPSC-CM provides a versatile new tool that may tremendously improve our understanding of the disease mechanisms. Consequently, these cells have been widely applied to study the complexity of cardiac disease. However, cardiomyopathies are divided into four classes, each with a distinct pathophysiology, resulting in various types of heart failure. The most common cardiomyopathy, HCM, is characterized by increased cardiac mass due to left ventricular wall thickening (hypertrophy) that most often is asymmetric, with particular involvement of the interventricular septum, myocytes disarray, and cardiac fibrosis [30]. DCM is characterized by left ventricular chamber enlargement and systolic dysfunction, which often leads to heart failure, arrhythmia, and sudden death. ACM predominantly affects right ventricular cardiomyocytes and occurs due to defects in the cardiac desmosome as a consequence of mutations in key desmosomal components, but also because of ion channel defects. Consequently, ACM hallmarks include right ventricular dilation, scarring, exaggerated lipogenesis and lipid infiltration, and arrhythmias. Finally, LVNC is characterized by cardiac noncompaction, primarily resulting in trabeculation and deep recesses in the left ventricle. Many studies performed in patient-derived hiPSC-CM have often recapitulated these respective hallmarks of inherited cardiomyopathies and thereby markedly increased our understanding of underlying molecular mechanisms, as summarized in Table 1. In addition to cardiomyopathies, inherited arrhythmias are generally caused by a pathological mutation in a gene encoding an ion channel or an associated protein. However, this review focusses on cardiomyopathies, whereas arrhythmias are

[13] Hypertrophic and noncompacted cardiomyopathy of left ventricle: different manifestations of the same disease

  • Authors: V. P. Pejčinović, V. Peršić, M. Boban, M. Rakić, Helena Antić Kauzlarić et al.
  • Year: 2017
  • Venue: Unknown venue
  • URL: https://www.semanticscholar.org/paper/c3ad9915af15ba9e02ea0c3aa49ec0a70d0229b5
  • DOI: 10.15836/CCAR2017.135
  • Citations: 1
  • Summary: A patient is presented with clear overlapping pheenotyp for LVNC and HCM, using the imaging method cardiac MRI, and it is speculated that mutations in sarcomere protein genes known to cause hypertrophic cardiomyopathy and dilated cardiopathy may be associated with left ventricular noncompaction.
  • Evidence snippets:
  • Snippet 1 (score: 0.449) > B3, which codes the protein Cypher/ZASP, genes of the internal nuclear membrane proteins (LMNA, which encodes lamin A/C) and even genes that code sarcomeric proteins like cardiac alpha-actin and the beta-myosin heavy chain and cardiac troponin T. The clinical picture of both diseases, HCM and LVNC, varies from mild forms until severe forms with heart failure and complex ventricular arrhythmias. LVNC and HCM may appear as overlapping entities. Cases of patients sharing both the LVNC and HCM phenotypes have been already published, and it is speculated that mutations in sarcomere protein genes known to cause hypertrophic cardiomyopathy and dilated cardiomyopathy may be associated with left ventricular noncompaction.1-5 In our case report, we are presenting patient with clear overlapping pheenotyp for LVNC and HCM, using the imaging method cardiac MRI. Vesna Pehar Pejčinović*, Viktor Peršić, Marko Boban, Marijana Rakić, Helena Antić Kauzlarić, Vladimir Peša

[14] 2017 Riley Heart Center Symposium on Cardiac Development: Development and Repair of the Ventricular Wall

  • Authors: L. Field, W. Shou, L. Markham
  • Year: 2018
  • Venue: Pediatric Cardiology
  • URL: https://www.semanticscholar.org/paper/230fb86b1eda43dc80b4fe54e8e4b801d389dfc2
  • DOI: 10.1007/s00246-018-1942-4
  • PMID: 30066104
  • PMCID: 6096844
  • Citations: 1
  • Summary: The 5th Riley Heart Center Symposium was held in Indianapolis, Indiana, on November 20, 2017, and sessions focused on the genetic regulation of cardiac development, the role of cell polarity in ventricular wall morphogenesis, the cell and molecular basis for arrhythmic cardiomyopathies, and cell cycle-based interventions to promote myocardial regeneration.
  • Evidence snippets:
  • Snippet 1 (score: 0.448) > Abnormal heart morphogenesis can result in congenital heart defects (CHDs) or inherited cardiomyopathies. Inappropriate gene expression [1, 2], expression of mutant gene products [3, 4], and exposure to cardiotoxic chemicals [5] or drugs [6] are all known to promote CHDs. The resulting structural defects (exemplified by heterotaxy, atrial and ventricular septal defects, noncompaction, etc.) render heart pump function inadequate. Nearly 1% of all newborns will have a structural heart defect [7], and the majority of these are severe enough to cause death in the absence of surgical and/or other palliative intervention. Inherited cardiomyopathies (that is, abnormalities of the sarcomere) [8, 9] constitute another important class of CHDs. While much is known about the clinical sequelae of CHDs, in many cases, the underlying molecular etiology remains undefined. For example, visceral heterotaxy results from the loss of left–right patterning during early embryogenesis, when the cell and molecular signaling cascades, which normally regulate sidedness pattern formation, are well-established. However, the spectrum of cardiac defects in many heterotaxy models and within patients with heterotaxy is more severe than what would be anticipated from a simple breakdown of sidedness patterning. The molecular basis for this is not understood. Similarly, the anatomical and clinical sequelae resulting from anomalies in ventricular septation and papillary muscle morphogenesis are well characterized. Moreover, multiple genes have been identified, which when dysregulated impact the development of these structures. How dysregulated gene expression mechanistically gives rise to these morphogenic defects is at best poorly understood. A similar case can be made for events that regulate maturation of the ventricular wall. Left ventricular noncompaction (LVNC) is recognized as a distinct form of cardiomyopathy, which results from a morphogenic defect. However, the molecular processes that underlie this defect are not well understood; understanding the underlying molecular mechanisms which give rise to LVNC is critical to effect improvements in diagnosis and care [10]. To promote interactions between clinical and basic

[15] Inherited cardiomyopathies.

  • Authors: J. Towbin
  • Year: 2014
  • Venue: Circulation journal : official journal of the Japanese Circulation Society
  • URL: https://www.semanticscholar.org/paper/6936a7dda78e293648fd18864be60e9a468e2516
  • DOI: 10.1253/circj.cj-14-0893
  • PMID: 25186923
  • Citations: 50
  • Influential citations: 1
  • Summary: Left ventricular noncompaction cardiomyopathy (LVNC) is an overlap disorder and it appears that any of these "final common pathways" can be involved depending on the specific form of LVNC.
  • Evidence snippets:
  • Snippet 1 (score: 0.448) > Cardiomyopathies (ie, diseases of the heart muscle) are major causes of morbidity and mortality. A significant percentage of patients with cardiomyopathies have genetic-based, inheritable disease and, over the past 2 decades the genetic causes of these disorders have been increasingly discovered. The genes causing these disorders when they are mutated appear to encode proteins that frame a "final common pathway" for that specific disorder, but the specifics of the phenotype, including age of onset, severity, and outcome is variable for reasons not yet understood. The "final common pathways" for the classified forms of cardiomyopathy include the sarcomere in the primarily diastolic dysfunction disorders hypertrophic cardiomyopathy and restrictive cardiomyopathy, the linkage of the sarcomere and sarcolemma in the systolic dysfunction disorder dilated cardiomyopathy, and the desmosome in arrhythmogenic cardiomyopathy. Left ventricular noncompaction cardiomyopathy (LVNC) is an overlap disorder and it appears that any of these "final common pathways" can be involved depending on the specific form of LVNC. The genetics and mechanisms responsible for these clinical phenotypes will be described.

[16] Spatial Transcriptomic Analysis of Focal and Normal Areas of Myocyte Disarray in Human Hypertrophic Cardiomyopathy

  • Authors: Jason Laird, Gayani Perera, R. Batorsky, Hongjie Wang, K. Arkun et al.
  • Year: 2023
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/25eb86bd5813dca0914c125c2c6a06c78999df82
  • DOI: 10.3390/ijms241612625
  • PMID: 37628806
  • PMCID: 10454036
  • Citations: 8
  • Influential citations: 1
  • Summary: A spatial transcriptomic analysis of the areas of focal myocyte disarray compared to areas of normal tissue using a commercially available platform identifies novel and potential disease-modifying targets for therapy in HCM.
  • Evidence snippets:
  • Snippet 1 (score: 0.438) > Hypertrophic Cardiomyopathy (HCM) is an inherited disorder affecting between 1 in 500 and 1 in 200 people (OMIM 192600, 115195, 115196, 115197 and others). The disease is characterized by unexplained left ventricular hypertrophy that is often asymmetric, involves the interventricular septum, and is associated with left ventricular outflow tract (LVOT) obstruction, fibrosis, microvascular occlusion, and sudden cardiac death. Histologically, it is characterized by focal areas of myocyte hypertrophy, myocyte disarray, fibrosis and medial hyperplasia. Anatomically, it is characterized by mitral valve abnormalities and left ventricular outflow tract obstruction. Physiologically, it is characterized by enhanced contractile function, reduced diastolic function and increased risk of sudden cardiac death [1]. Traditionally, HCM is considered a disease that ensues from sarcomere gene dysfunction, but in most patients, pathogenic sarcomere gene mutations cannot be identified. In those patients where pathogenic gene mutations are found, most are located in the sarcomere genes MYBPC3 and MYH7. The genetic landscape of HCM is well-summarized [2]. The activation of signaling pathways that promote cardiac myocyte hypertrophy and fibrosis of the heart have been implicated in many studies [3], but additional mechanisms are likely contributing. Comprehensive studies to understand how sarcomere gene mutations can lead to phenotypes not related to sarcomere function or those seen in cells that do not express sarcomere genes are lacking in the field. Since sarcomere gene mutation-negative patients have similar phenotypes to sarcomere gene mutation-positive patients, it is likely that there are final common pathological pathways independent of sarcomere gene mutations that are involved, but these final common pathways are incompletely understood. Recent reports using single-nucleus RNA sequencing of human HCM tissue have identified potential alterations in cell-to-cell communication involving extracellular matrix proteins, integrin receptors and the activation of immune cells as potential contributors to the HCM phenotype [4][5][6].

[17] Screening for dilated cardiomyopathy in immediate family members: to whom, how, when (and where)

  • Authors: M. Pieroni, M. Ciabatti, C. Zocchi
  • Year: 2024
  • Venue: European Heart Journal Supplements : Journal of the European Society of Cardiology
  • URL: https://www.semanticscholar.org/paper/9d12e21d05e5bdad6ea72e27cfe86abc1abfe06f
  • DOI: 10.1093/eurheartjsupp/suae024
  • PMID: 38784151
  • PMCID: 11110450
  • Summary: Screening of family members of patients affected by DCM represents an important tool for early diagnosis, treatment, and prognostic stratification and it is important that family screening and follow-up of identified patients are carried out in units dedicated to the treatment and study of cardiomyopathies.
  • Evidence snippets:
  • Snippet 1 (score: 0.438) > Abstract Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilation and systolic dysfunction in the absence of coronary artery disease, valvular disease, congenital heart disease, or altered haemodynamic conditions. Dilated cardiomyopathy can recognize multiple aetiologies, including infectious processes, effect of toxic substances, immunological mechanisms, and genetic causes. In recent years, many genes coding for proteins involved in the structure and function of the cardiomyocytes have been associated with the development of DCM, making the identification of familial forms increasingly frequent. At the same time, an ever-increasing use of cardiac magnetic resonance imaging has made it possible to identify early morpho-functional alterations in subjects with initial forms of the disease, or carriers of pathogenic genetic variants. The increasingly in-depth understanding of the genetic and molecular mechanisms operating in DCM has also favoured the development of new therapeutic strategies including drugs with molecular targets and gene therapies. In this panorama, screening of family members of patients affected by DCM represents an important tool for early diagnosis, treatment, and prognostic stratification. In relation to its clinical relevance and its complexity, it is important that family screening and follow-up of identified patients are carried out in units dedicated to the treatment and study of cardiomyopathies.

[18] Left Ventricular Noncompaction Associated with Hypertrophic Cardiomyopathy: Morphologic and Functional Evaluation with Multidetector CT

  • Authors: H. Lee, Jae-Wook Lee, F. Meinel, U. Schoepf
  • Year: 2019
  • Venue: Cardiovascular Imaging Asia
  • URL: https://www.semanticscholar.org/paper/d871ca8c8ad851d43d59e03a33fdfbcc452181df
  • DOI: 10.22468/CVIA.2018.00255
  • Summary: With these cases showing a combination of two rare cardiac diseases, the utility of cardiac CT for the anatomical assessment of coronary arteries and the evaluation of ventricular morphology and function is emphasized.
  • Evidence snippets:
  • Snippet 1 (score: 0.437) > namic chamber and no other cardiac or systemic disease [1,3]. HCM is one of the most common genetic cardiac diseases, with a reported prevalence of around 0.2%. The imaging diagnosis of HCM is based on a maximal LV wall thickness ≥15 mm in the end-diastolic phase [1,5]. HCM is associated with a wide variety of phenotypes and a diverse clinical course, including sudden cardiac death in young adults [1,3]. HCM follows as a Mendelian autosomal dominant inheritance pattern and is caused by a missense mutation in one of the sarcomeric genes that encode cardiac sarcomeric protein [1,2,4]. The pathologic hallmark of HCM is myocyte disorganization/disarray, which is widespread throughout the LV and, to a lesser extent, in the right ventricle. > LV noncompaction is a rare cardiomyopathy, with a prevalence of less than 0.02%, characterized by excessive trabeculations of the LV with two distinct layers of NC and C myocardium. It is diagnosed and also differentiated from hypertrabeculation by a ratio of NC/C myocardium >2.0 at end-systole on echocardiography, and >2.3 at end-diastole on MR [6]. The natural history of LV noncompaction is unclear. Patients may be asymptomatic or suffer from dyspnea, arrhythmia, and systolic heart failure, thromboembolic events secondary to atrial fibrillation, or sudden cardiac death. Although not much is known about its inheritance pattern, LV noncompaction is a genetically heterogeneous entity with a sporadic and familial form [2]. > Recently, different mutations in sarcomeric genes, which previously have been found to be involved in the pathogenesis of HCM, have been also identified in patients with isolated LV noncompaction without myocardial hypertrophy. Thus, there seems to be a shared genetic origin of these two different cardiomyopathic phenotypes [1][2][3][4]6].

[19] Extracellular vesicles in cardiomyopathies: A narrative review

  • Authors: A. Rizzuto, A. Faggiano, C. Macchi, S. Carugo, C. Perrino et al.
  • Year: 2023
  • Venue: Heliyon
  • URL: https://www.semanticscholar.org/paper/d9f9d3f5e11a4f42af7d1ead3cff3c874fff64a4
  • DOI: 10.1016/j.heliyon.2023.e23765
  • PMID: 38192847
  • PMCID: 10772622
  • Citations: 5
  • Influential citations: 1
  • Summary: The aims of this narrative review are to elucidate the potential role of EVs in the paracrine cell-to-cell communication among cardiac tissue compartments, in aiding the diagnosis of the diverse subtypes of cardiomyopathies in a minimally invasive manner, and to address whether certain molecular and phenotypical characteristics of EVs may correlate with cardiomyopathy disease phenotype and severity.
  • Evidence snippets:
  • Snippet 1 (score: 0.437) > Cardiomyopathies refer to myocardial disorders affecting the heart muscle, in which structural and functional abnormalities are observed, in the absence of diseases such as coronary artery disease, hypertension, valvular disease, or congenital heart disease that could account for the observed abnormalities. According to the 2023 European Society of Cardiology (ESC) guidelines for the management of cardiomyopathies, morphological traits (ventricular hypertrophy: left and/or right; ventricular dilation: left and/or right; non-ischemic ventricular scar) and functional characteristics (global and/or regional ventricular systolic and/or diastolic dysfunction) are clinically employed to categorize five distinct cardiomyopathy phenotypes: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), non-dilated left ventricular cardiomyopathy (NDLVC), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). Furthermore, the guidelines also specify the existence of syndromic and metabolic cardiomyopathies, including Anderson-Fabry disease, RASopathies, Friedreich ataxia, and Glycogen storage disorders [4]. > Whilst this phenotypic description is essential in paving the diagnostic and therapeutic pathway, the exact evolving nature of cardiomyopathies, along with their underlying aetiological complexities, are yet to be fully elucidated [5]. Within this context, biomarkers represent putative tools for identifying high-risk patients in a prompt manner, unveiling potential risk associations with disease progression and outcomes, and may also provide insights on unexplored molecular mechanisms at the basis of the pathophysiology of these disorders. > Thus, the aim of the present narrative review is to summarize the current knowledge on EVs in the setting of cardiomyopathies and to elucidate whether certain molecular and phenotypical characteristics of EVs (e.g., miRNA content) may correlate with cardiomyopathy phenotypes and severity.

[20] Left Ventricular Noncompaction

  • Authors: A. Almeida
  • Year: 2017
  • Venue: Unknown venue
  • URL: https://www.semanticscholar.org/paper/68fc2309bef159675fd75eb39dda0a58d7a29dfd
  • DOI: 10.5772/66291
  • Citations: 1
  • Summary: Left ventricular noncompaction (LVNC) is accepted as an unclassified (the American Heart Association) or a genetic cardiomyopathy (the European Society of Cardiology), but some argue that this phenotype may be a morphologic trait shared by different cardiomyopathies. This chapter covers the state of the art on the pathology, underly ing mechanisms, its clinical manifestations, and diagnosis and treatment modalities of LVNC. LVNC may be defined as follows: an inner non‐compacted layer with pro...
  • Evidence snippets:
  • Snippet 1 (score: 0.435) > Left ventricular noncompaction (LVNC) is accepted as an unclassified (the American Heart Association) or a genetic cardiomyopathy (the European Society of Cardiology), but some argue that this phenotype may be a morphologic trait shared by different cardiomyopathies. This chapter covers the state of the art on the pathology, underly ing mechanisms, its clinical manifestations, and diagnosis and treatment modalities of LVNC. LVNC may be defined as follows: an inner non‐compacted layer with prominent left ventricular trabeculae and deep intertrabecular recesses and a thin outer compacted layer. Mechanisms are still debatable, with the hypothesis of compaction arrest during embryogenesis as the most accepted theory. Genetic data support LVNC as a distinct cardiomyopathy, although evidence for LVNC as a shared morphological trait is not ruled out, since LVNC may be associated with other cardiomyopathies, congenital heart diseases and in some cases may be acquired. Diagnosis is based on imaging and may be confirmed by the use of genetics. Clinical picture and prognosis and the management options are discussed.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.