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Background: Genomic and epigenomic dynamics both play critical roles during embryogenesis. Zfp57 maintains genomic imprinting with both maternal and zygotic functions. In our previous study, we found that maternal and zygotic Zfp57 modulate NOTCH signaling during cardiac development. In this study, we investigated Zfp57 mutants from E11.5 to E13.5 to delineate its function during cardiac development. Results: Here, we describe novel roles of maternal and zygotic Zfp57 during cardiovascular system development. We found that maternal and zygotic Zfp57 was required for coronary vascular development. Maternal and zygotic loss of Zfp57 perturbed the sprouting of the sinus venosus‐derived endothelial cells and led to underdeveloped coronary vasculature, meanwhile, there was an ectopic overproduction of blood islands over the ventricles. Furthermore, loss of Zfp57 and failed vasculature disturbed myocardium maturation. Loss of maternal and zygotic Zfp57 resulted in hyper trabeculation and failed myocardium compaction. Zfp57 zygotic mutant (M+Z−) hearts displayed noncompaction cardiomyopathy at E18.5. Conclusions: Our results suggest that maternal and zygotic ZFP57 are essential for coronary vascular formation and myocardium maturation in mice. Our research provides evidence for the role of genomic imprinting during embryogenesis. Key Findings: Zfp57 ablation results in cardiovascular development failure in mice [ABSTRACT FROM AUTHOR]

Abstract Background There has been an increase in the reporting of cases of left ventricular noncompaction (LVNC) cardiomyopathy in medical literature due to advances in medical imaging. Patients with LVNC may be asymptomatic or may present with arrhythmias, heart failure, thromboembolism or sudden death. LVNC is typically diagnosed by echocardiography, although there are higher-resolution cardiac imaging techniques such as cardiac magnetic resonance imaging (MRI) to make the diagnosis. The objective of the study is to report on a series of 9 cases of LVNC cardiomyopathy seen at the University College Hospital, Ibadan. Cases of LVNC seen between September 1, 2015 and July 31, 2022 in our echocardiography service is being reported. Results There were a total of 6 men and 3 women. Mean age at presentation was 52.89 ± 15.02 years. The most common mode of presentation was heart failure (6 patients). Hypertension was the most common comorbidity (6 patients). Three patients had an ejection fraction of less than 40% and the mean ratio of noncompacted to compacted segment at end-systole was 2.80 ± 0.48. The most common areas of trabecular localization were the LV lateral wall and the apex. Beta blockers were highly useful in the management of the patients. Conclusions LVNC cardiomyopathy is not uncommon in our environment and a high index of suspicion is often required.

IntroductionThe 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.MethodsWe 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”.ResultsOf 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.DiscussionThe 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.

Cardiomyopathies may be hereditary and associated with a familial predilection. Morbidity and mortality can be caused by heart failure, sudden death, or arrhythmias. Sometimes these events are the first manifestations of cardiovascular disease. Hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy are perhaps most thoroughly studied in that context. Dilated cardiomyopathy, although most frequently of secondary etiology, has a significant familial cluster. Noncompaction of the left ventricle can sometimes be seen in healthy individuals and, in other instances, is associated with severe LV dysfunction. Genetic testing is of utmost importance, since it might allow for the identification of individuals carrying mutations predisposing them to these diseases. In addition, certain variants may benefit from tailored therapeutic regimens, and thus searching for a causal mutation can impact clinical practice and is recommended for all patients with HCM or ACM. Patients with DCM and positive family history should be included as well. Regular follow-ups are advised, even in those with negative phenotypes, because these disorders are often age dependent. During pregnancy and in the case of athletes, special consideration should be made as well. We intend to summarize the most current evidence regarding their management. [ABSTRACT FROM AUTHOR]

In gestation, the coronary circulation develops initially in the compact layer and it expands only in fetal development to the trabeculations. Conflicting data have been published as to whether the trabecular layer is hypoperfused relative to the compact wall after birth. If so, this could explain the poor pump function in patients with left ventricular excessive trabeculation, or so-called noncompaction. Here, we review direct and indirect assessments of myocardial perfusion in normal and excessively trabeculated hearts by in vivo imaging by magnetic resonance imaging (MRI), positron emission tomography (PET)/single photon emission computed tomography (SPECT), and echocardiography in addition to histology, injections of labelled microspheres in animals, and electrocardiography. In MRI, PET/SPECT, and echocardiography, flow of blood or myocardial uptake of blood-borne tracer molecules are measured. The imaged trabecular layer comprises trabeculations and blood-filled intertrabecular spaces whereas the compact layer comprises tissue only, and spatio-temporal resolution likely affects measurements of myocardial perfusion differently in the two layers. Overall, studies measuring myocardial uptake of tracers (PET/SPECT) suggest trabecular hypoperfusion. Studies measuring the quantity of blood (echocardiography and MRI) suggest trabecular hyperperfusion. These conflicting results are reconciled if the low uptake from intertrabecular spaces in PET/SPECT and the high signal from intertrabecular spaces in MRI and echocardiography are considered opposite biases. Histology on human hearts reveal a similar capillary density of trabecular and compact myocardium. Injections of labelled microspheres in animals reveal a similar perfusion of trabecular and compact myocardium. In conclusion, trabecular and compact muscle are likely equally perfused in normal hearts and most cases of excessive trabeculation. [Display omitted] • Hypoperfusion of excessive trabeculations has been proposed to cause myopathy • We review data from PET/SPECT, MRI, echocardiography, microspheres, histology, and ECG • Technical biases of measuring perfusion in the trabecular layer are discussed • Little support for preferential hypoperfusion of excessive trabeculations • Trabecular and compact myocardium are likely equally perfused [ABSTRACT FROM AUTHOR]

Abstract Cardiomyopathy is the most common presenting feature of Barth syndrome, often presenting in infancy with severe heart failure and cardiac dysfunction. Historically, affected infants commonly died early after presentation, sometimes before a diagnosis of Barth syndrome was made. With increases in awareness of Barth syndrome and in the care of infants with severe heart failure, survival of children with Barth syndrome and severe heart failure has improved. We describe our experience caring for five unrelated boys with Barth syndrome who presented with severe cardiomyopathy and heart failure prior to age 2 who have had marked improvement with long‐term response to medical heart failure therapy.

We report an extremely rare case of left ventricular noncompaction (LVNC) cardiomyopathy sparing the anterior ventricular wall in an interesting “necklace” pattern in parasternal short axis view in a 76-year-old female with frequent palpitation and shortness of breath for the last 6 months. Interestingly, the patient had a plethora of basal septal premature ventricular complexes (PVCs) both from the anterior and posterior aspects of the paradoxically thinned-out basal septum and they were not from the segment of noncompacted (NC) myocardium. Our case is unique and the first to describe the LVNC in an interesting shape of “necklace” sparing the left ventricular anterior, anteroseptal, and anterolateral wall and paradoxically arising plethora of septal PVCs from the thinned-out basal septum deteriorating the left ventricular function rapidly in an elderly female in her seventh decade of life. Although commonly in LVNC, the PVCs arise from the NC segment, in this unique case plethora of PVCs paradoxically arising from the basal septum were contributing toward rapid deterioration of left ventricular systolic function in an elderly patient in her seventh decade of life without the presence of conventional risk factors.

BACKGROUND:Current diagnostic criteria for noncompaction cardiomyopathy (NCC) lack specificity, and the disease lacks prognostic indicators. Reverse apical rotation (RAR) with abnormal rotation of the cardiac apex in the same clockwise direction as the base has been described in adults with NCC. The aim of this study was to test the hypothesis that RAR might differentiate between symptomatic NCC and benign hypertrabeculations and might be associated with ventricular dysfunction. METHODS:Echocardiograms from 28 children with NCC without cardiac malformations were prospectively compared with those from 29 age-matched normal control subjects. A chart review was performed to identify the patients' histories and clinical characteristics. Speckle-tracking was used to measure longitudinal strain, circumferential strain, and rotation. RESULTS:RAR occurred in 39% of patients with NCC. History of left ventricular (LV) dysfunction or arrhythmia was universal in, but not exclusive to, patients with RAR. Patients with RAR had lower LV longitudinal strain but similar ejection fractions compared with patients without RAR (median, -15.6% [interquartile range, -12.9% to -19.3%] vs -19% [interquartile range, -14.5% to -21.9%], P < .01; 53% [interquartile range, 43% to 68%] vs 61% [interquartile range, 58% to 67%], P = .08). Only a pattern of contraction with RAR, early arrest of twisting by mid-systole, and premature untwisting was associated with lower ejection fraction (46%; interquartile range, 43% to 52%; P = .006). CONCLUSIONS:RAR is not a sensitive but is a specific indicator of complications in children with NCC. Therefore, RAR may have prognostic rather than diagnostic value. Premature untwisting of the left ventricle during ejection may be an even more worrisome indicator of LV dysfunction.

We report an extremely rare case of left ventricular noncompaction (LVNC) cardiomyopathy sparing the anterior ventricular wall in an interesting "necklace" pattern in parasternal short axis view in a 76-year-old female with frequent palpitation and shortness of breath for the last 6 months. Interestingly, the patient had a plethora of basal septal premature ventricular complexes (PVCs) both from the anterior and posterior aspects of the paradoxically thinned-out basal septum and they were not from the segment of noncompacted (NC) myocardium. Our case is unique and the first to describe the LVNC in an interesting shape of "necklace" sparing the left ventricular anterior, anteroseptal, and anterolateral wall and paradoxically arising plethora of septal PVCs from the thinned-out basal septum deteriorating the left ventricular function rapidly in an elderly female in her seventh decade of life. Although commonly in LVNC, the PVCs arise from the NC segment, in this unique case plethora of PVCs paradoxically arising from the basal septum were contributing toward rapid deterioration of left ventricular systolic function in an elderly patient in her seventh decade of life without the presence of conventional risk factors. [ABSTRACT FROM AUTHOR]

Takotsubo syndrome (TTS) and left ventricular hypertrabeculation/noncompaction (LVHT) have in common that they are only diagnosed since 1990. Diagnostic criteria and prognosis of affected patients are still debated and the knowledge about etiology and pathogenesis of both disorders is limited. Both abnormalities are associated with neurologic and neuromuscular disorders (NMD). We summarize the data about the relationship between TTS, LVHT and NMD. We identified 8 case reports about the co-incidence of TTS and LVHT (6 females, 2 males, age 0–76 years). In 2/8 cases recurrent TTS occurred after 8 and 10 months. In most of the patients, LVHT was diagnosed together with TTS, thus, it cannot be assessed if LVHT was present since birth or developed during life-time. In one case, LVHT was absent in a previous echocardiogram, developed de novo during TTS, and disappeared after 3 months. In 4/8 patients follow-up were reported, and in all of them, regression or disappearance of LVHT was observed. NMD or psychiatric disorders were reported in 7/8 patients. We conclude —limited by the small number of cases—that patients with LVHT and TTS seem to be frequently associated with NMD and have a high risk of recurrence. LVHT seems to disappear after TTS, but it remains unclear whether trabeculations in fact regress or are still present, but not more visible because of a decrease in left ventricular size resulting in smaller spaces between the trabeculations. Patients with LVHT and TTS require long-term follow-up to assess any changes of these abnormalities over time.

MYH7, encoding the myosin heavy chain sarcomeric β‐myosin heavy chain, is a common cause of both hypertrophic and dilated cardiomyopathy. Additionally, families with left ventricular noncompaction cardiomyopathy (LVNC) and congenital heart disease (CHD), typically septal defects or Ebstein anomaly, have been identified to have heterozygous pathogenic variants in MHY7. One previous case of single ventricle CHD with heart failure due to a MYH7 variant has been identified. Herein, we present a single center's experience of complex CHD due to MYH7 variants. Three probands with a history of CHD, LVNC, and/or arrhythmias were identified to have MYH7 variants through multigene panel testing or exome sequencing. These three patients collectively had 12 affected family members, four with a history of Ebstein anomaly and seven with a history of LVNC. These findings suggest a wider phenotypic spectrum in MYH7‐related CHD than previously understood. Further investigation into the possible role of MYH7 in CHD and mechanism of disease is necessary to fully delineate the phenotypic spectrum of MYH7‐related cardiac disease. MYH7 should be considered for families with multiple individuals with complex CHD in the setting of a family history of LVNC or arrhythmias. [ABSTRACT FROM AUTHOR]

NF-κB is a major transcription factor regulating cell survival, organ development and inflammation, but its role in cardiac development has been inadequately explored. To examine this function, we generated mice in which IKKβ, an essential kinase for NF-κB activation, was constitutively activated in embryonic cardiomyocytes. For this purpose, we used smooth muscle-22α (SM22α)-Cre mice, which are frequently used for gene recombination in embryonic cardiomyocytes. Embryonic hearts of SM22αCre-CA (constitutively active) IKKβflox/flox mice revealed remarkably thin, spongy and hypoplastic myocardium. In exploring the mechanism, we found that the expression of bone morphogenetic protein 10 (BMP10) and T-box transcription factor 20 (Tbx20), major regulators of cardiac development, was significantly downregulated and upregulated, respectively, in the SM22αCre-CAIKKβflox/flox mice. We also generated NK2 homeobox 5 (Nkx2.5) Cre-CAIKKβflox/wt mice since Nkx2.5 is also expressed in embryonic cardiomyocytes and confirmed that the changes in these genes were also observed. These results implicated that the activation of NF-κB affects cardiac development. • Constitutive-active IKKβ in SM22α-expressing cells including embryonic cardiomyocytes induces non-compaction phenotype. • Constitutive activation of IKKβ in cardiomyocytes modifies the expression of BMP10 and Tbx20. • This study would give some information about how viral or bacterial infection during pregnancy causes congenital heart diseases. [ABSTRACT FROM AUTHOR]

A definitively diagnosed case of left ventricular noncompaction (LVNC) has not been previously reported in a non-human species. We describe a Maine Coon cross cat with echocardiographically and pathologically documented LVNC. The cat was from a research colony and was heterozygous for the cardiac myosin binding protein C mutation associated with hypertrophic cardiomyopathy (HCM) in Maine Coon cats (A31P). The cat had had echocardiographic examinations performed every 6 months until 6 years of age at which time the cat died of an unrelated cause. Echocardiographic findings consistent with LVNC (moth-eaten appearance to the inner wall of the mid- to apical region of the left ventricle (LV) in cross section and trabeculations of the inner LV wall that communicated with the LV chamber) first were identified at 2 years of age. At necropsy, pathologic findings of LVNC were verified and included the presence of noncompacted myocardium that consisted of endothelial-lined trabeculations and sinusoids that constituted more than half of the inner part of the LV wall. The right ventricular (RV) wall also was affected. Histopathology identified myofiber disarray, which is characteristic of HCM, although heart weight was normal and LV wall thickness was not increased.

Although left ventricular (LV) aneurysm is a well-described complication of ischemic heart disease, it may less frequently develop in the setting of normal coronary anatomy and myocardial blood supply. LV noncompaction (LVNC) is a particularly rare etiology of LV aneurysm; in the few cases previously reported in the literature, non-surgical management was pursued. In this report, we discuss the surgical repair of an 'idiopathic' LV aneurysm in a patient who presented with multiple thromboembolic events, with LVNC as the likely etiology on the underlying LV pathology. < Learning objective: Left ventricular (LV) noncompaction represents a rare etiology of LV aneurysm; although non-surgical management of this condition has been previously reported, we demonstrate that early surgical intervention is an acceptable treatment option.> [ABSTRACT FROM AUTHOR]

Forty two year old female with rheumatoid arthritis presented with breathlessness on exertion. ECG was in sinus rhythm, right axis deviation of QRS, and poor progression of R wave. Echocardiogram showed right ventricular dilatation and apical crypts. Cardiac MRI confirmed the crypts and noncompaction of the right ventricle. Isolated noncompaction of right ventricle(NCRV) is very rare and is only mentioned in a few case reports. The embryology, diagnostic criteria extrapolated from the noncompaction of left ventricle, and the clinical course of NCRV are reviewed. This rare disease has been associated with rheumatoid arthritis for the first time.

Sphingosine 1-phosphate (S1P) is a bioactive lipid that acts via G protein-coupled receptors. The S1P receptor S1P1, encoded by S1pr1, is expressed in developing heart but its roles there remain largely unexplored. Analysis of S1pr1 LacZ knockin embryos revealed β-galactosidase staining in cardiomyocytes in the septum and in the trabecular layer of hearts collected at 12.5 days post coitus (dpc) and weak staining in the inner aspect of the compact layer at 15.5 dpc and later. Nkx2-5-Cre- and Mlc2a-Cre-mediated conditional knockout of S1pr1 led to ventricular noncompaction and ventricular septal defects at 18.5 dpc and to perinatal lethality in the majority of mutants. Further analysis of Mlc2a-Cre conditional mutants revealed no gross phenotype at 12.5 dpc but absence of the normal increase in the number of cardiomyocytes and the thickness of the compact layer at 13.5 dpc and after. Consistent with relative lack of a compact layer, in situ hybridization at 13.5 dpc revealed expression of trabecular markers extending almost to the epicardium in mutants. Mutant hearts also showed decreased myofibril organization in the compact but not trabecular myocardium at 12.5 dpc. These results suggest that S1P signaling via S1P1 in cardiomyocytes plays a previously unknown and necessary role in heart development in mice.

The mouse fetal and adult hearts express two adenine nucleotide translocator (ANT) isoform genes. The predominant isoform is the heart-muscle-brain ANT-isoform gene 1 (Ant1) while the other is the systemic Ant2 gene. Genetic inactivation of the Ant1 gene does not impair fetal development but results in hypertrophic cardiomyopathy in postnatal mice. Using a knockin X-linked Ant2 allele in which exons 3 and 4 are flanked by loxP sites combined in males with a protamine 1 promoter driven Cre recombinase we created females heterozygous for a null Ant2 allele. Crossing the heterozygous females with the Ant2(fl), PrmCre(+) males resulted in male and female ANT2-null embryos. These fetuses proved to be embryonic lethal by day E14.5 in association with cardiac developmental failure, immature cardiomyocytes having swollen mitochondria, cardiomyocyte hyperproliferation, and cardiac failure due to hypertrabeculation/noncompaction. ANTs have two main functions, mitochondrial-cytosol ATP/ADP exchange and modulation of the mitochondrial permeability transition pore (mtPTP). Previous studies imply that ANT2 biases the mtPTP toward closed while ANT1 biases the mtPTP toward open. It has been reported that immature cardiomyocytes have a constitutively opened mtPTP, the closure of which signals the maturation of cardiomyocytes. Therefore, we hypothesize that the developmental toxicity of the Ant2 null mutation may be the result of biasing the cardiomyocyte mtPTP to remain open thus impairing cardiomyocyte maturation and resulting in cardiomyocyte hyperproliferation and failure of trabecular maturation. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

The ventricular walls of the human heart comprise an outer compact layer and an inner trabecular layer. In the context of an increased pre‐test probability, diagnosis left ventricular noncompaction cardiomyopathy is given when the left ventricle is excessively trabeculated in volume (trabecular vol >25% of total LV wall volume) or thickness (trabecular/compact (T/C) >2.3). Here, we investigated whether higher spatial resolution affects the detection of trabeculation and thus the assessment of normal and excessively trabeculated wall morphology. First, we screened left ventricles in 1112 post‐natal autopsy hearts. We identified five excessively trabeculated hearts and this low prevalence of excessive trabeculation is in agreement with pathology reports but contrasts the prevalence of approximately 10% of the population found by in vivo non‐invasive imaging. Using macroscopy, histology and low‐ and high‐resolution MRI, the five excessively trabeculated hearts were compared with six normal hearts and seven abnormally trabeculated and excessive trabeculation‐negative hearts. Some abnormally trabeculated hearts could be considered excessively trabeculated macroscopically because of a trabecular outflow or an excessive number of trabeculations, but they were excessive trabeculation‐negative when assessed with MRI‐based measurements (T/C <2.3 and vol <25%). The number of detected trabeculations and T/C ratio were positively correlated with higher spatial resolution. Using measurements on high resolution MRI and with histological validation, we could not replicate the correlation between trabeculations of the left and right ventricle that has been previously reported. In conclusion, higher spatial resolution may affect the sensitivity of diagnostic measurements and in addition could allow for novel measurements such as counting of trabeculations. [ABSTRACT FROM AUTHOR]

Understanding the overall variant burden in pediatric patients with left ventricular noncompaction (LVNC) has clinical implications. Whole exome sequencing (WES) allows detection of coding variants in both candidate cardiomyopathy genes and those included on commercial panels. Other lines of evidence, including in silico analysis, are necessary to reduce the overwhelming number of variants to those most likely having a phenotypic impact. Five families, including five pediatric probands with LVNC, 5 other affected, and 10 unaffected family members, had WES performed, followed by bioinformatics filtering and Sanger sequencing. Review of the HGMD, variant classification by ACMG guidelines, and clinical information were used to further refine complex genotypes. One nonsense and eleven missense variants were identified. In Family 1, affected siblings carried digenic heterozygous variants: E1350K- MYH7 and A276V- ANKRD1. The proband also carried heterozygous W143X- NRG1. Four affected members of Family 2 carried K184Q- MYH7 while unaffected members did not. In Family 3, homozygous A161T -MYH7 and heterozygous P4935T- OBSCN variants were identified in the proband with the latter being absent in his unaffected brother. In Family 4, proband's father and half-sibling have mild hypertrabeculation and carry T3796I- PLEC. The proband, carrying T3796I- PLEC and V2878A- OBSCN , demonstrated higher trabeculation burden. The proband in Family 5 carried four variants, R3247W- PLEC , C92Y- ERG , T1233M- NCOR2, and E54K- HIST1H4B. Application of ACMG criteria and clinical data revealed that W143X- NRG1 , P4935T- OBSCN , and V2878A- OBSCN likely have no phenotypic role. We report nine variants, including novel T3796I- PLEC and biallelic A161T-MYH7 , likely contributing to phenotypes ranging from asymptomatic hypertrabeculation to severe LVNC with heart failure. • This study uses familial whole exome sequencing, in silico analysis, ACMG variant interpretation, and genotype-phenotype correlation with clinical data to identify novel genetic variants in pediatric left ventricular noncompaction cardiomyopathy (LVNC) with clinical characteristics ranged from asymptomatic hypertrabeculation to infantile presentation and eventual HFrEF necessitating hospitalization. • Eleven missense variants and one nonsense variant were confirmed with Sanger sequencing. • No reports have been found in the ClinVar database for 7 variants (E1350K- MYH7 , W143X- NRG1 , P4935T- OBSCN , A161T- MYH7, C92Y- ERG , T1233M- NCOR2, and E54K- HIST1H4B). • This is the first report of missense variants, heterozygous T3796I- PLEC and biallelic A161T -MYH7 , causing LVNC. • We highlight that variants previously reported as "benign", "likely benign", or "VUS," according to ACMG, may be clinically significant when identified in combination with others and that MYH7 variants remain a primary driver of disease. [ABSTRACT FROM AUTHOR]

A 32-year-old male patient was admitted to the hospital with syncope. An electrocardiogram revealed complete atrioventricular (AV) block and a right bundle branch block with a QRS duration of 218 milliseconds. The heart rate was 40 beats/minute. Echocardiography revealed that both AV valves opened to a single ventricle as well as noncompaction of the myocardium. Due to New York Heart Association class III heart failure, cardiac resynchronization therapy with a defibrillator device (CRT-D) was performed. After the implantation, the electrocardiography QRS duration was reduced to 183 ms. To our knowledge, this was the first reported case of CRT-D implantation in a patient with a noncompacted single ventricle and complete AV block.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The ventricular trabecular layer is crucial in embryonic life. In adults, the proportion of trabecular-to-compact myocardium varies substantially between individuals, within individuals over time, and yet exhibits almost no correlation to pump function since most individuals with excessive trabeculation are asymptomatic. The question of how functional is the myocardium of the trabecular layer, relative to the myocardium of the compact layer, has been difficult to answer but it is often assumed to be inferior. An answer is now emerging from recent advances and it can improve our understanding of how the trabecular layer impacts on pathogenicity. This narrative review concerns natural variation in trabeculation, tissue organization, transcriptomics, immunohistochemistry, vascularization, electrical propagation, diastolic function and compliance, systolic function, and ejection fraction. There are no overt transcriptional differences in the adult stage, and the myocardium is equally equipped with sarcomeric proteins, mitochondria, and vascular supply. The similar structural features are consistent with myocardium with a similar stroke work per gram tissue, along with a high ejection fraction of the trabecular layer. In conclusion, the myocardium of the trabecular and compact layers is highly similar and this offers a logical explanation for the reproducible observations that most individuals with excessive trabeculation are asymptomatic., Competing Interests: Declaration of competing interest The authors declare that there is no competing interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Takotsubo syndrome (TTS) and left ventricular hypertrabeculation/noncompaction (LVHT) have in common that they are only diagnosed since 1990. Diagnostic criteria and prognosis of affected patients are still debated and the knowledge about etiology and pathogenesis of both disorders is limited. Both abnormalities are associated with neurologic and neuromuscular disorders (NMD). We summarize the data about the relationship between TTS, LVHT and NMD. We identified 8 case reports about the co-incidence of TTS and LVHT (6 females, 2 males, age 0-76 years). In 2/8 cases recurrent TTS occurred after 8 and 10 months. In most of the patients, LVHT was diagnosed together with TTS, thus, it cannot be assessed if LVHT was present since birth or developed during life-time. In one case, LVHT was absent in a previous echocardiogram, developed de novo during TTS, and disappeared after 3 months. In 4/8 patients follow-up were reported, and in all of them, regression or disappearance of LVHT was observed. NMD or psychiatric disorders were reported in 7/8 patients. We conclude -limited by the small number of cases-that patients with LVHT and TTS seem to be frequently associated with NMD and have a high risk of recurrence. LVHT seems to disappear after TTS, but it remains unclear whether trabeculations in fact regress or are still present, but not more visible because of a decrease in left ventricular size resulting in smaller spaces between the trabeculations. Patients with LVHT and TTS require long-term follow-up to assess any changes of these abnormalities over time. [ABSTRACT FROM AUTHOR]

We present a rare case of left ventricular noncompaction (LVNC) in a 23-year-old female with recurrent syncope with electrocardiography documentation of apical septal ventricular tachycardia (VT). Abnormal embryological myocardial maturation presenting as LVNC with electrogenic heterogenity across the noncompacted spongiform segments result in recurrent VT and mandates automated intracardiac defibrillator implantation (AICD). These subsets of patients in spite of AICD implantation require life-long broad-spectrum antiarrythmic in the form of amiodarone and beta-blocker to prevent a crisis of VT storm or sudden cardiac death.

Background: Left ventricular noncompaction cardiomyopathy (LVNC CMP) is a genetic cardiomyopathy. Genotype-phenotype correlation and clinical outcome of genetic variants in pediatric and adult LVNC CMP patients are still unclear.Methods: The retrospective multicenter study was conducted in unrelated index patients with LVNC CMP, diagnosed between the years 1987 and 2017, and all available family members. All index patients underwent next-generation sequencing for genetic variants in 174 target genes using the Illumina TruSight Cardio Sequencing Panel. Major adverse cardiac events (MACE) included mechanical circulatory support, heart transplantation, survivor of cardiac death, and/or all-cause death as combined endpoint.Results: Study population included 149 LVNC CMP patients with a median age of 27.8 (9.2–44.8) years at diagnosis; 58% of them were symptomatic, 18% suffered from non-sustained and sustained arrhythmias, and 17% had an implantable cardioverter defibrillator (ICD) implanted. 55/137 patients (40%) were ≤ 18 years at diagnosis.A total of 134 variants were identified in 87/113 (77%) index patients. 93 variants were classified as variant of unknown significance (VUS), 24 as likely pathogenic and 15 as pathogenic. The genetic yield of (likely) pathogenic variants was 35/113 (31%) index patients. Variants occurred most frequently in MYH7 (n=19), TTN (n = 10) and MYBPC3 (n = 8). Altogether, sarcomere gene variants constituted 42.5% (n = 57) of all variants. The presence or absence of (likely) pathogenic variants or variants in specific genes did not allow risk stratification for MACE.Reduced left ventricular (LV) systolic function and increased left ventricular end-diastolic diameter (LVEDD) were risk factors for event-free survival in the Kaplan-Meier analysis. Through multivariate analysis we identified reduced LV systolic function as the main risk factor for MACE. Patients with reduced LV systolic function were at a 4.6-fold higher risk for MACE.Conclusions: Genetic variants did not predict the risk of developing a MACE, neither in the pediatric nor in the adult cohort. Multivariate analysis emphasized reduced LV systolic function as the main independent factor that is elevating the risk for MACE. Genetic screening is useful for cascade screening to identify family members at risk for developing LVNC CMP.

Introduction: Left ventricular hypertrabeculation, also named 'noncompaction' (LVHT) is a cardiac abnormality which is detected by pathoanatomic investigation or during cardiac surgery. Imaging techniques visualize LVHT by ventriculography, echocardiography, cardiac magnetic resonance imaging (CMRI) and computed tomography (CT). Areas covered: We aimed to assess 1) how often the definition of LVHT was validated against a criterion standard, 2) if inter- and intra-observer agreement was assessed, and 3) how often LVHT was associated with genetic diseases. A literature search disclosed 58 cases whose hearts were investigated pathoanatomically and by ≥1 imaging technique. Echocardiography was most frequently (95%) compared with pathoanatomy, followed by cMRI (31%), ventriculography (7%) and CT (5%). Intra- and inter-observer agreement was more frequently assessed for cMRI definitions and yielded more consistent results than for echocardiographic definitions. Since genetic findings were only reported from 4 of the 58 cases, no association with imaging findings could be carried out. Expert opinion: Correlation between pathoanatomic investigations with imaging techniques will hopefully contribute to reliable and uniformly accepted definitions of LVHT. Most probably, the echocardiographic definition of LVHT will be a synthesis of the currently used definitions, integrating short axis and four-chamber views. A refinement of cMRI definitions, considering pathoanatomic and echocardiographic investigations, seems necessary to avoid overdiagnosis. [ABSTRACT FROM AUTHOR]

There is a presentation of the results of a two-year follow-up after surgical treatment of a patient with chronic heart failure and a permanent form of atrial fibrillation, in which isolated apex hypoplasia and non-compaction of left ventricular myocardium were revealed.

Background: There are limited data on ventricular arrhythmias (VAs) associated with left ventricular noncompaction (LVNC) cardiomyopathy.Objectives: This study aims to analyze the clinical and electrocardiographic characteristics of VAs in a group of patients with LVNC.Methods: Forty-two nonrelated patients with LVNC and VAs were included that were evaluated at the Inherited Cardiac Disease Unit of the University Hospital Virgen Arrixaca (Murcia-Spain) (ERN Guard-Heart Centre, European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart).Results: Thirteen patients (30.9%) had isolated LVNC, 27 (64.3%) had LVNC associated with dilated cardiomyopathy, and 2 (4.8%) had LVNC associated with hypertrophic cardiomyopathy. Among isolated LVNC individuals, 9 (69.2%) had premature ventricular complexes (PVCs)/nonsustained ventricular tachycardias (VTs), and 4 (30.8%) VTs (1 VT degenerating in ventricular fibrillation). In the dilated cardiomyopathy group, 11 (40.7%) patients had PVCs, 14 (51.9%) VTs, and 2 (7.4%) ventricular fibrillation. In the hypertrophic cardiomyopathy group, one patient had PVCs and the other VTs. Endocardial mapping and ablation were performed in 19 patients (45.2%): 7 ventricular outflow tracts (4 right ventricular outflow tract, 1 left coronary cusp, and 2 right coronary cusp), 2 in the left ventricular summit, 5 related to Purkinje potentials at the mid inferoseptal area, and 5 associated with endocardial scar localized in the basal anterolateral and inferolateral segments. Epicardial ablation was performed in 3 cases.Conclusion: The substrate of VAs in LVNC cardiomyopathy is heterogeneous, with origin in ventricular outflow tracts, Purkinje system related, and resembling scar patterns in nonischemic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis are genetic disorders due to deficiency of lysosomal enzymes, resulting in abnormal glycosaminoglycans accumulation in several tissues. Heart involvement tends to be progressive and worsens with age. We describe the first case of mucopolysaccharidosis type I presenting with noncompaction/dilated-mixed cardiomyopathy and heart failure within neonatal period, which responded successfully to specific metabolic treatment. Cardiac function recovered after enzyme replacement therapy and hematopoietic stem cell transplantation, adding to the existing knowledge of the disease.

Background The prognosis of left ventricular noncompaction (LVNC) remains elusive despite its recognition as a clinical entity for >30 years. We sought to identify clinical and imaging characteristics and risk factors for mortality in patients with LVNC. Methods and Results 339 adults with LVNC seen between 2000 and 2016 were identified. LVNC was defined as end‐systolic noncompacted to compacted myocardial ratio >2 (Jenni criteria) and end‐diastolic trough of trabeculation‐to‐epicardium (X):peak of trabeculation‐to‐epicardium (Y) ratio 2.3 (Petersen criteria) by magnetic resonance imaging. Median age was 47.4 years, and 46% of patients were female. Left ventricular ejection fraction

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

Trabeculation exhibits highly varied presentations, whereas noncompaction (NC) is a specific disease entity based arithmetically on wall thickness. We aimed to evaluate the clinical implications of trabeculation and its relevance to outcomes. A total of 296 patients (age 63 ± 12 years; 64% men) with trabeculation who underwent echocardiography were retrospectively identified between January 2011 and December 2012. Analyses were conducted on distinguished trabeculation which was divided into NC (maximum noncompacted/compacted ratio ≥ 2.0) or hypertrabeculation (HT) (ratio < 2.0). We evaluated features of trabeculation and explored cardiovascular (CV) outcome events (coronary revascularization, hospitalization for worsening heart failure (HF), stroke, nonsustained ventricular tachycardia (VT), implantation of an implantable cardioverter defibrillator (ICD), and CV death). Over a mean of 4.2 years, CV outcome events occurred in 122 (41%) patients who were older and exhibited an increased frequency of diabetes mellitus, stroke, implantation of ICD, HF and dilated cardiomyopathy. The frequencies of NC or HT, the trabeculation ratio and its manifestation were similar among patients with and without events. NC/HT with concomitant apical hypocontractility and worsening systolic function were univariable predictors of adverse events. On multivariable analysis, concomitant apical hypocontractility on NC/HT remained significant (hazard ratio 8.94, 95% confidence interval 2.9–27.2, p < 0.001) together with old age, HF and increased E/e′ ratio. NC/HT with concomitant apical hypocontractility provided clues about the current medical illness and aided in risk stratification. [ABSTRACT FROM AUTHOR]

Congenital dyserythropoietic anemia type 1 (CDA1) is a rare autosomal recessive disease characterized by macrocytic anemia, ineffective erythropoiesis, and secondary hemochromatosis. Left-ventricular noncompaction (LVNC) is a cardiomyopathy that is commonly attributed to intrauterine arrest of normal compaction during the endomyocardial morphogenesis. LV hypertrabeculation/noncompaction (LVHT/NC) morphology, however, might exist in various hemoglobinopathies. Our primary objective was to determine whether the pattern of LVHT/NC is more prevalent among patients with CDA1, in comparison to subjects without CDA1, and to find potential risk factors for LVHT/NC among these patients. Our secondary objective was to evaluate the clinical implication of LVHT/NC. We retrospectively assessed 32 CDA1 patients (median age 17.5, range 6–61) that underwent routine assessment of iron overload by cardiac magnetic resonance. Number and distribution of noncompacted LV segments were assessed in CDA1 patients and compared to 64 age- and gender-matched patients without CDA1. The ratio of noncompacted to compacted myocardium (NC/C ratio) in end-diastole was calculated for each of the three long-axis views. NC/C ratio > 2.3 was considered diagnostic for LVHT/NC. In multivariate analysis, the presence of CDA1 was independently associated with NC/C ratio > 2.3, a feature of LVHT/NC (adjusted OR = 11.46, 95%CI = 2.6–50.68, p =.001). CDA1 was strongly associated with increased number of myocardial segments exhibiting LVHT/NC pattern. Cardiac volumes and ejection fraction were preserved without clinical adverse events in long term follow-up. CDA1 patients have a higher prevalence of LVHT/NC than normal individuals, independent of myocardial iron overload and without effect on ejection fraction or clinical outcome. • CDA1 is a rare autosomal recessive disease. • CMR is routinely used to detect myocardial iron overload in CDA1 patients. • LVNC morphology was detected by CMR in most of our CDA1 patients. • The severity of LVNC was independent of myocardial iron levels. [ABSTRACT FROM AUTHOR]

Background: Left ventricular (LV) hypertrabeculation fulfilling noncompaction cardiomyopathy criteria has been detected in athletes. However, the association between LV noncompaction (LVNC) phenotype and vigorous physical activity (VPA) in the general population is disputed.Objectives: The aim of this study was to assess the relationship between LVNC phenotype on cardiac magnetic resonance (CMR) imaging and accelerometer-measured physical activity (PA) in a cohort of middle-aged nonathlete participants in the PESA (Progression of Early Subclinical Atherosclerosis) study.Methods: In PESA participants (n = 4,184 subjects free of cardiovascular disease), PA was measured by waist-secured accelerometers. CMR was performed in 705 subjects (mean age 48 ± 4 years, 16% women). VPA was recorded as total minutes per week. The study population was divided into 6 groups: no VPA and 5 sex-specific quintiles of VPA rate (Q1 to Q5). The Petersen criterion for LVNC was evaluated in all subjects undergoing CMR. For participants meeting this criterion (noncompacted-to-compacted ratio ≥2.3), 3 more restrictive LVNC criteria were also evaluated (Jacquier, Grothoff, and Stacey).Results: LVNC phenotype prevalence according to the Petersen criterion was significantly higher among participants in the highest VPA quintile (Q5 = 30.5%) than in participants with no VPA (14.2%). The Jacquier and Grothoff criteria were also more frequently fulfilled in participants in the highest VPA quintile (Jacquier Q5 = 27.4% vs. no VPA = 12.8% and Grothoff Q5 = 15.8% vs. no VPA = 7.1%). The prevalence of the systolic Stacey LVNC criterion was low (3.6%) and did not differ significantly between no VPA and Q5.Conclusions: In a community-based study, VPA was associated with a higher prevalence of CMR-detected LVNC phenotype according to diverse established criteria. The association between VPA and LVNC phenotype was independent of LV volumes. According to these data, vigorous recreational PA should be considered as a possible but not uncommon determinant of LV hypertrabeculation in asymptomatic subjects. [ABSTRACT FROM AUTHOR]

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A definitively diagnosed case of left ventricular noncompaction (LVNC) has not been previously reported in a non‐human species. We describe a Maine Coon cross cat with echocardiographically and pathologically documented LVNC. The cat was from a research colony and was heterozygous for the cardiac myosin binding protein C mutation associated with hypertrophic cardiomyopathy (HCM) in Maine Coon cats (A31P). The cat had had echocardiographic examinations performed every 6 months until 6 years of age at which time the cat died of an unrelated cause. Echocardiographic findings consistent with LVNC (moth‐eaten appearance to the inner wall of the mid‐ to apical region of the left ventricle (LV) in cross section and trabeculations of the inner LV wall that communicated with the LV chamber) first were identified at 2 years of age. At necropsy, pathologic findings of LVNC were verified and included the presence of noncompacted myocardium that consisted of endothelial‐lined trabeculations and sinusoids that constituted more than half of the inner part of the LV wall. The right ventricular (RV) wall also was affected. Histopathology identified myofiber disarray, which is characteristic of HCM, although heart weight was normal and LV wall thickness was not increased.

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