Left Ventricular Noncompaction Research Articles

LEFT VENTRICULAR NON COMPACTION CARDIOMYOPATHY ASSOCIATED WITH MITRAL VALVE PROLAPSE

Left ventricular non compaction (LVNC) is a rare condition characterized by prominent ventricular trabeculations and intertrabecular recesses,Mitral regurgitationwhen present is usually a result of annular dilation, mitral valve prolapse due to chordae tendinae rupture is quite rare.We present the case of a 48 year old male with no medical history who presented with worsening exertional dyspnea classified as NYHA class III. The physical examination found a systolic murmur heard at the apex. Transthoracic echocardiography and cardiac magnetic resonance confirmed the diagnosis of Left ventricular non compaction associated with posterior mitral valve prolapse with severe mitral regurgitation and preserved ventricular function who was successfully operated and found asymptomatic during the follow up.

ABLE-SCORE: a simplified risk score for major adverse cardiovascular outcomes in patients with left ventricular noncompaction

Abstract Background Left ventricular noncompaction (LVNC) is a heterogeneous entity with life-threatening complications and variable prognosis [1,2]. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVNC is comparatively complex for clinical practice [3,4]. Purpose To develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVNC. Methods This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVNC patients between January 2009 and December 2020 at a single national-level medical center (derivation cohort n=300; internal validation cohort n=129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort n=95). The derivation/internal validation cohorts and the multicenter external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors for MACE in the multivariable Cox regression predictive model, and underwent both internal and external validation to confirm its discrimination (Harrell’s C-index), calibration (calibration plots), and clinical applicability (decision curve analysis). Results A total of 524 LVNC patients (43.5 ± 16.6 years, 65.8% male) were included in the study. At the end of the follow-up, 97 (32.3%), 38 (29.5%), and 20 (21.1%) individuals in the derivation, internal validation, and external validation cohort experienced at least one endpoint of MACE. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement and left ventricular ejection fraction≤40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell’s C-index of 0.821 (95%CI 0.772-0.869), 0.786 (95%CI 0.703-0.869), and 0.750 (95%CI 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVNC. According to decision curve analysis, the ABLE-SCORE displayed greater net benefit than the currently existing risk score for MACE in LVNC [3], indicating its strength in clinical applicability. Conclusions Derived from readily available laboratory and echocardiographic variables, a simplified and efficient risk score for MACE was developed and validated using a large LVNC cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVNC.Development of the ABLE-SCOREValidation of the ABLE-SCORE

Characterisation of the novel SCN5A-P1891A variant, implicated in left ventricular noncompaction cardiomyopathy in a Finnish family, using human induced pluripotent stem cell-derived cardiomyocytes

Abstract Introduction Left ventricular noncompaction (LVNC) is a heterogenous cardiomyopathy characterised by an extensively trabeculated left ventricle (LV). Several genetic variants that perturb trabeculae compaction, and thus LV maturation, have been reported [1]. However, the precise mechanisms underpinning this have proven contentious with, for example, differentially aberrant cardiomyocyte proliferation implicated in the development of LVNC [2,3]. Purpose In this study, we investigate a novel SCN5A variant, P1891A, which is associated with LVNC in a Finnish family. We ascertain the effects of this variant through the characterisation of variant-carrying human induced pluripotent stem cell-derived cardiomyocytes (P1891A-hiPSC-CMs). Methods We isolated dermal fibroblasts from a symptomatic member of a Finnish family carrying the SCN5A-P1891A variant; derived P1891A-hiPSCs via nucleofection with reprogramming plasmids [4]; and differentiated these into hiPSC-CMs alongside healthy control-hiPSCs. We determined the action potential (AP) and sodium- (INa) and calcium-current (ICa) densities of hiPSC-CMs via patch-clamp. We investigated gene expression in hiPSC-CMs through qPCR and employed Multiple Approaches Combined (MCA) proteomics [5] in SCN5A-transfected HEK293-like cells to elucidate protein-protein interactions (PPI). We subjected hiPSC-CMs to mechanical stretch [6] to examine their stress response and assessed their proliferation capacity via high-content analysis for the percentage of BrdU positive hiPSC-CMs following mitogenic stimulation (5 µM CHIR99021 and 1 µM SB203580). Finally, we ascertained contractile kinetics and apparent contractile force using fibrin hydrogel-based engineered heart tissues (EHTs) [7]. Results The P1891A-hiPSC-CMs demonstrated elevated INa density alongside enhanced arrhythmogenicity relative to healthy control hiPSC-CMs although, AP kinetics and ICa density were unperturbed (Fig. 1). Under baseline conditions, P1891A-hiPSC-CMs exhibited higher SCN5A gene expression and proteomics revealed a reduction in PPI. Baseline proliferation was unchanged; however, aged P1891A-hiPSC-CMs had enhanced proliferative capacity following mitogenic stimulation. Further, the P1891A-hiPSC-CMs displayed impaired tolerance to mechanical stretch as evidenced by upregulated NPPB and ACTA1 expression. In the context of the EHT, P1891A-hiPSC-CMs yielded disparate phenotypes. Whilst a subset compacted fully and yielded weaker contractile parameters relative to healthy control EHTs, the majority of P1891A-hiPSC-CM EHTs failed to fully compact thereby recapitulating the LVNC phenotype (Fig. 2). Conclusions This study presents a unique aetiology of LVNC and links, for the first time, SCN5A mutations with enhanced human cardiomyocyte proliferation. The ability to recapture the noncompaction phenotype in EHTs presents a powerful model for future mechanistic research and drug development.

Prevalence and clinical significance of left ventricular thrombus discovered by pathological examination in explanted hearts of patients with end-stage cardiomyopathy

Abstract Objective We sought to determine the prevalence of anatomic LV thrombus detected by pathological examination of explanted hearts in patients with end-stage cardiomyopathy (CM) who have undergone heart transplantation, and to examine the relationship between anatomic LV thrombus missed by cardiac imaging and thromboembolic events. Methods and results A total of consecutive 148 explanted hearts from patients (44 years; 80% were men) undergoing heart transplantation were examined. The most common etiology of end-stage heart failure was dilated CM (53%). Of 148 explanted hearts, LV thrombus was present in 19 patients/hearts (13%). Excluding patients with ischemic CM (n=7), LV thrombus was present in 8 DCMs (9%), 1 genetic associated with LV noncompaction (100%), 2 hypertrophic CM (25%), and 1 arrhythmogenic CM (14%). None of patients with cardiac sarcoidosis (n=5) had LV thrombus. Of these patients, 11 (58%) received anticoagulants with favorable numbers of time in therapeutic range. No patient in the cohort had history of thromboembolic event before heart transplantation. Only 11 patients (26 %) with pathological evidence of LV thrombus had LV thrombus detected by previous echocardiograms (median time difference from echocardiogram to heart transplantation = 170 days). Six of 19 patients with anatomic LV thrombus had undergone cardiac MRI; LV thrombus had been detected in 2 patients (33%). The most common site of missed LV thrombus was LV cavity (where thrombi did not attach to any particular LV endocardial surface) followed by LV apex (Figure). Conclusion The prevalence of LV thrombus found by pathological examination in end-stage heart diseases was 13 % despite anticoagulation in most patients. However, the presence of these thrombi did not cause any serious thromboembolic events. Anatomic LV thrombi were missed by echocardiography/cardiac MRI in approximately 70% of patients. Genetic associated LV noncompaction and HCM were the most 2 prevalent CMs with anatomic thrombi, while none of patients with cardiac sarcoidosis had evidence of LV thrombus. Further study in thromboembolic milieu involving endocardial surface in specific type of CM may be needed.

Morphological, electrophysiological, and molecular alterations in foetal noncompacted cardiomyopathy induced by disruption of ROCK signalling.

Left ventricular noncompaction cardiomyopathy is associated with heart failure, arrhythmia, and sudden cardiac death. The developmental mechanism underpinning noncompaction in the adult heart is still not fully understood, with lack of trabeculae compaction, hypertrabeculation, and loss of proliferation cited as possible causes. To study this, we utilised a mouse model of aberrant Rho kinase (ROCK) signalling in cardiomyocytes, which led to a noncompaction phenotype during embryogenesis, and monitored how this progressed after birth and into adulthood. The cause of the early noncompaction at E15.5 was attributed to a decrease in proliferation in the developing ventricular wall. By E18.5, the phenotype became patchy, with regions of noncompaction interspersed with thick compacted areas of ventricular wall. To study how this altered myoarchitecture of the heart influenced impulse propagation in the developing and adult heart, we used histology with immunohistochemistry for gap junction protein expression, optical mapping, and electrocardiography. At the prenatal stages, a clear reduction in left ventricular wall thickness, accompanied by abnormal conduction of the ectopically paced beat in that area, was observed in mutant hearts. This correlated with increased expression of connexin-40 and connexin-43 in noncompacted trabeculae. In postnatal stages, left ventricular noncompaction was resolved, but the right ventricular wall remained structurally abnormal through to adulthood with cardiomyocyte hypertrophy and retention of myocardial crypts. Thus, this is a novel model of self-correcting embryonic hypertrabeculation cardiomyopathy, but it highlights that remodelling potential differs between the left and right ventricles. We conclude that disruption of ROCK signalling induces both morphological and electrophysiological changes that evolve over time, highlighting the link between myocyte proliferation and noncompaction phenotypes and electrophysiological differentiation.

Searching for genetic determinants for left ventricular non-compaction.

Left ventricular non-compaction (LVNC) is still a pathology around which there are numerous controversies regarding the criteria for its diagnosis, presentation, prognosis, and even classification into the appropriate group of diseases. So far, about 190 genes in which mutations may be associated with LVNC have been described, and in each of them, several to several dozen different loci have been discovered. We decided to analyze the frequency of single nucleotide variants (SNVs) in correlation to Petersen's criteria. We retrospectively analyzed the results of cardiac magnetic resonance (CMR) studies. Twenty-three patients who met Petersen's criteria agreed to participate in the research and take blood samples for genetic testing. Next, we prospectively included 24 volunteers who did not meet Petersen's criteria. Petersen's criteria were complied with ratio of non-compacted to compacted myocardium (NC/C) ≥2.3. A total of 47 DNA samples were analyzed based on the selected regions of the following genes: β-myosin heavy chain (MYH7), α-cardiac actin (ACTC1), cardiac troponin T (TNNT2), myosin binding protein-C (MYBPC3), LIM-domain binding protein 3 (LBD3), and taffazin (TAZ). In total, 248 substitutions in exons and introns were obtained for all analyzed samples. No statistically significant differences were detected between the mentioned groups. No significant difference in either downward or upward trends in the number of substitutions in relation to the increasing trabeculation is observed. We indicated differences in the occurrence of the studied SNVs between groups, especially for rs8037241 (3'UTR region of ACTC1) and rs2675686 (LDB3), but they also did not show statistical significance. Although we did not find a significant correlation between the co-occurrence of individual mutations with LVNC, it is worth noting that the presence of one of the four mutations in the range rs8037241 (ACTC1 3'UTR), rs3729998 (TNNT2e. 12), and rs727503240 (MYH7e. 39) increases the risk of LVNC more than 4 times. An inverse association between the number of SNVs and the meeting the Petersen's criteria was demonstrated for studied LDB3 region and rs397516254 in exon 39 of the MYH7 gene. To our knowledge, no studies have been published comparing the prevalence of selected SNVs in a group of healthy subjects and in a group meeting the Petersen criteria for LVNC. Among both completely healthy individuals who did not meet the Petersen criteria for LVNC as well as those with symptoms who met these criteria we found a similar incidence of SNVs in the ACTC1, TNNT2, LDB3 and MYH7 genes segments analyzed. Further studies are required to confirm or exclude "potentially protective" SNV in the 39th exon of MYH7 (rs397516254) and the role of co-occurrence of individual SNVs in rs8037241 (ACTC1 3'UTR), rs3729998 (TNNT2), and rs727503240 (MYH7) for the increase of the risk of LVNC.

Prevalence, Clinical Manifestations, and Adverse Outcomes of Left Ventricular Noncompaction in Adults: A Systematic Review and Meta-Analysis.

Left ventricular noncompaction (LVNC) is recognized within the spectrum of adult cardiomyopathies for its unique pathophysiologic features and clinical challenges. This condition exhibits a wide range of clinical manifestations, from asymptomatic states to severe cardiovascular complications, making its diagnosis and management challenging. This study aimed to synthesize current data on the prevalence, diagnostic methods, clinical outcomes, and treatment efficacy of LVNC in adults to address gaps in understanding and management strategies. A systematic review and meta-analysis of research from 2000 to March 2024 was conducted, focusing on studies involving adults diagnosed with LVNC. This approach aimed to collect data on the prevalence of LVNC, the diagnostic accuracy of different imaging modalities, clinical manifestations, and the impact of different treatment strategies. The study showed a prevalence of LVNC of 0.5%, with cardiovascular magnetic resonance outperforming echocardiography in diagnosis with a detection rate of 1.3%. Mortality and heart transplantation rates were 12% and 7%, respectively. Significant predictors of adverse outcomes included New York Heart Association (NYHA) class III or IV, ventricular tachycardia, and reduced left ventricular ejection fraction (LVEF), guiding a nuanced approach in tailoring therapeutic strategies to optimize patient care and outcomes. This study advances the understanding of LVNC by refining diagnostic criteria and evaluating management strategies, highlighting the superiority of cardiovascular magnetic resonance. It identifies predictors of adverse outcomes and assesses treatment efficacy, urging precision in diagnosis and tailored treatments. Its comprehensive analysis and methodological rigor make it a key resource advocating a multidisciplinary approach to improve patient outcomes in LVNC.

A CASE OF LEFT VENTRICULAR NON COMPACTION CARDIOMYOPATHY WITH ATRIAL SEPTAL DEFECT

Left ventricular non-compaction (LVNC) is a rare form of cardiomyopathy characterized by abnormal myocardial trabeculations and deep recesses within the left ventricle. It is often associated with other congenital heart defects, such as atrial septal defects (ASD). This report discusses the case of a 5-year-old female with both LVNC and ASD, highlighting the clinical presentation, diagnostic challenges, and management strategies. The case emphasizes the importance of early detection and a multidisciplinary approach to optimize patient outcomes. Recent literature is reviewed to provide updated insights into the pathophysiology, diagnosis, and treatment of this rare condition.

Cardiomyopathy-Associated Chronic HeartFailure in Infants Aged

There have been few large-scale studies on the outcomes of cardiomyopathy-associated heart failure (HF) in infants aged <1 year. This study aimed to assess longitudinal echocardiographic outcomes of infants with HF secondary to cardiomyopathy who survived for >1 year. A prospective observational study following 327 infant patients up to 5 years in 2 large pediatric heart centers in Northern China between January 2010 and December 2018. A total of 236 (72.2%) patients had reduced left ventricular ejection fraction (LVEF) (HF with reduced ejection fraction group; LVEF <40%), 91 (27.8%) patients had midrange LVEF (HF with midrange ejection fraction group; LVEF ≥40% but <55%). LVEF improved significantly within the first year and remained stable in years 2 through 5 for both groups. The HF with midrange ejection fraction group had a higher rate of LVEF normalization (hazard ratio, 1.65; P<0.001). Baseline LVEF ≥40%, baseline left ventricular end-diastolic diameter Z score <7.8, the absence of left bundle-branch block, and the absence of β-blocker use were 4 independent favorable predictors for future LVEF normalization. A total of 62.4% of enrolled patients were diagnosed with left ventricular noncompaction. No significant difference in LVEF normalization was found among the different types of cardiomyopathy studied. A significant number of infants with cardiomyopathy who survived >1 year were found to improve with medical therapies during the first year of diagnosis. Poorer outcomes were associated with decreased LVEF and increased heart size at diagnosis baseline, the presence of left bundle-branch block and use of β blockers. The Northern Chinese pediatric population may have a high proportion of left ventricular noncompaction.

Left Ventricular Non-Compaction: Evolving Concepts

Left ventricular non-compaction (LVNC) is a rare heart muscle disease defined by the presence of prominent left ventricular trabeculation, deep intertrabecular recesses, and a thin compact layer. Several hypotheses have been proposed regarding its pathogenesis, with the most recently accepted one being that compact layer and trabeculated layers develop independently according to an “allometric growth”. The current gold-standard diagnostic criteria (in particular, the Petersen index non-compaction/compaction ratio &gt; 2.3) reflect an excess of myocardial trabeculation, which is not a specific morpho-functional feature of LVNC cardiomyopathy but merely a “phenotypic trait”, even described in association with other myocardial disease and over-loading conditions. Accordingly, the European Society of Cardiology (ESC) guidelines have definitively abolished the term ‘LVNC cardiomyopathy’. Recently, evolving perspectives led to the restoration of LVNC cardiomyopathy by distinguishing “hypertrabeculation phenotype” and “non-compaction phenotype”. It has been proposed that the disease-specific pathophysiologic mechanism is a congenitally underdevelopment of the compact layer accounting for an impairment of the left ventricular systolic function. Future prospective research should focus on the clinical and prognostic relevance of compact layer thinning rather than excessive trabeculation, which could significantly influence the management of patients with LVNC. The review aims to update current knowledge on the pathogenesis, genetics, and diagnostic criteria of LVNC, offering modern insights for future perspectives.

Genophenotypic correlates and long-term outcome prognosticators of left ventricular non-compaction in children

BackgroundTo investigate the outcomes, clinical prognosticators, and genetic profiles of pediatric left ventricular non-compaction (LVNC). MethodsAll subjects were <18 years old, diagnosed with LVNC between January 2008 and December 2020. Whole-exome sequencing was undertaken. The primary endpoint was composite outcome, including death, heart transplant, and left ventricular assist device implantation. ResultsThirty-three patients were enrolled, males predominating (57.6%). Median age at diagnosis was 0.33 (0.1–7.2) years. Family history was documented in four (12.1%). Five (15.2%) had sustained arrhythmias. Mean follow-up period was 9.5 years, and 5- and 10-year event-free survival were 84.8% and 66.9%, respectively. Seven died of heart failure, four received heart transplants, and one required left ventricular assist device placement. Log of baseline NT-proBNP (adjusted odds ratio [aOR] = 4.4, p = 0.012) and lack of improvement in NT-proBNP (aOR = 41.2, p = 0.033) impacted the primary outcome most significantly. Eighteen out of 25 genetic testing (72%) revealed chromosomal anomalies, or pathogenic or likely pathogenic variants. Three genetic variants (PLEKHM2 p.G419R, RYR2 p.V2571A, and SCN5A p.M1676I) were significantly associated with the primary outcome (p = 1.52 × 10−6). ConclusionsPediatric LVNC is a rare disorder with variable genetic underpinnings. Baseline NT-proBNP values and lack of improvement in NT-proBNP levels were important predictors of poor long-term outcomes. Pathogenic genetic variants or chromosomal anomalies are not unusual.

Lack of Bridge to Recovery in Pediatric Dilated Cardiomyopathy With Left Ventricular Noncompaction

BackgroundThis study assessed the possibility of a bridge to recovery using the Berlin Heart EXCOR and the histologic characteristics of pediatric patients with dilated cardiomyopathy accompanied by a left ventricular noncompaction phenotype. MethodsOf the 17 pediatric patients with dilated cardiomyopathy who underwent Berlin Heart EXCOR implantation between 2013 and 2020, 6 were diagnosed with left ventricular noncompaction association. The patients were classified into 2 groups: the dilated cardiomyopathy group and dilated cardiomyopathy with the left ventricular noncompaction phenotype group. The histologic characteristics of the left ventricular myocardium and left ventricular function after Berlin Heart EXCOR implantation were compared. ResultsCardiac recovery was not observed in the dilated cardiomyopathy with left ventricular noncompaction group. In contrast, 6 patients (55%) in the dilated cardiomyopathy group achieved cardiac recovery, and the Berlin Heart EXCOR was explanted. The degree of myocardial fibrosis was significantly higher in the dilated cardiomyopathy with the left ventricular noncompaction phenotype group than in the dilated cardiomyopathy group (P < .05). The final follow-up left ventricular ejection fraction and end-diastolic diameter during Berlin Heart EXCOR support improved significantly compared with the preimplantation variables in the dilated cardiomyopathy group (both P < .001); the dilated cardiomyopathy with left ventricular noncompaction phenotype group showed no improvements (P = .84 and P = .37, respectively). ConclusionsThe left ventricular noncompaction phenotype associated with dilated cardiomyopathy may adversely affect the rate of cardiac recovery with Berlin Heart EXCOR.

Abstract Or125: Numb Family Proteins regulate left ventricular compaction by modulating autophagic process

Background: Left ventricular noncompaction (LVNC) is a type of cardiomyopathy, which patients manifest clinical features of heart failure, arrhythmias, thrombotic events, and sudden death. We previously found that the ablation of Numb(Nb) , and its homologue Numbl(Nl) at early stage, causes LVNC defects resulting in embryonic lethality. In this study, we found that mice with Nb and Nl deletion at later stage survive to adulthood and develop toLVNC cardiomyopathy. Method: We applied aMHC-Cre to delete and generate Nb and Nl double knockout (ADKO); examine the structure and functions of the ADKO hearts via echocardiography (ECHO); determine the heart arrhythmia via telemetry; determine the Nb subcellular localization via a Nb overexpression line (R26-Flag:mCherry:Numb); and determine the mechanistic function of NFPs in autophagy via autophagic reporter, electron microscopy, and molecular and biochemical assays. Results: The cTnT-Cre mediated Nb and Nl deletion causes LVNC and embryonic lethality, while the ADKO can survive to adulthood and died between eight- and twelve-month-old. The ADKO hearts display LVNC by two months of age, a reduced systolic function by four months old, and left ventricular remodeling and dilatation starting at six months old. ADKO hearts manifest major clinical features of LVNC, including arrhythmias and thrombosis. ADKO hearts exhibit significant accumulation of damaged mitochondria, autophagosomes and autophagolysosomes compared to controls. Biochemical analyses reveal elevated levels of p62 and a higher ratio of LC3II/LC3I in ADKO hearts. NFP null cells and ADKO hearts exhibit abnormal autophagic flux, characterized by arrested at autophagolysosome, increased expression of Lamp1 and Lamp2, but reduced levels of cathepsin D. Mass spectrometry analyses reveal Numb's interaction with proteins involved in endocytosis and autophagy. Consistently, Numb localizes to autophagosomes and autophagolysosomes. Conclusion: NFPs regulate left ventricular compaction at both embryonic and postnatal stages, suggesting that LVNC can be both congenital and acquired. As LVNC mice progress, they develop dilated cardiomyopathy (DCM) at later stage, suggesting that LVNC can occur independently at early stage, and is associated with DCM at later stage. Deletion of NFPs in cardiomyocytes disrupts endocytosis and autophagic flux. Our studies suggest that NFPs mediated endocytosis and autophagy are essential for left ventricular compaction.

Pathophysiological and Pedigree Analysis of Left Ventricular Noncompaction in Japanese Macaques (Macaca fuscata).

Left ventricular noncompaction (LVNC) involving genetic mutation is categorized as an unclassified cardiomyopathy, and its diagnostic criteria have not been standardized. This could be because precise animal models of LVNC have not been created in any laboratory animal species. This study aimed to analyze the pathophysiology and familial tendency of LVNC in Japanese macaques. Two Japanese macaques with LVNC, and their parents who were suspected of having cardiac disease, were examined. One macaque with LVNC was examined using chest radiography, echocardiography, cardiac biomarkers, cardiac MRI, and pathologic examination, and the other macaque was examined using chest radiography, echocardiography, and cardiac biomarkers. Their common father and the mother of one of the macaques with LVNC were tested for chest radiography and cardiac biomarkers. Echocardiography revealed a meshwork with trabeculation and deep intertrabecular recesses in all their left ventricular walls. The 2 macaques with LVNC demonstrated a layered appearance of the myocardium, consisting of noncompacted myocardium on the endocardial side and compacted myocardium on the epicardial side, with a noncompacted/compacted ratio of 6.0 and 5.8, respectively. One of the 2 macaques with LVNC (case 1) had elevated levels of troponin I, troponin T, atrial natriuretic peptide, and brain natriuretic peptide. The second macaque with LVNC (case 2) showed blood flow in the intertrabecular recesses on echocardiography. The common father (case 3) of the 2 macaques with LVNC and the mother (case 4) of one of the macaques with LVNC had elevated levels of troponin I and troponin T. In case 1, histopathologic examination revealed fibrous thickening of the endocardium, fibrosis of the myocardial interstitium, myocardial disarray, vacuolar degeneration, anisonucleosis, and necrosis of myocardial cells. This suggests that Japanese macaques could serve as a reliable animal model of human LVNC.

Assessing Left Ventricular Pathology in Patients with Ebstein Anomaly Using Cardiovascular Magnetic Resonance: Looking Past the Right Heart.

Ebstein Anomaly (EA) is a malformation of the right heart, but there is data to suggest that the left ventricle (LV) can suffer from intrinsic structural and functional abnormalities which affect surgical outcomes. The LV in patients with EA is hypertrabeculated with abnormalities in LV function and strain. In this retrospective single-center study, patients with EA who underwent pre-operative cardiac MRI (CMR) between the periods of 2014-2024 were included along with a group of healthy-age-matched controls. Left ventricular and right ventricular volume, function and strain analyses were performed on standard SSFP imaging. LV noncompacted: compacted (NC/C) ratio and the displacement index of the tricuspid valve were measured. Forty-seven EA patients were included with mean age of 21.0 ± 17.6years. Seventeen EA patients (36%) had mild pre-operative LV dysfunction on CMR and 1 (2.1%) had moderate LV dysfunction. Out of these 18 patients with LV dysfunction, only 2 were detected to have dysfunction on Echocardiogram. The global circumferential and longitudinal strain were significantly lower in the reduced LVEF group compared to those with preserved LVEF (-14.8% vs. -17%, p = 0.02 and - 11.9% vs. - 15.0%; p = 0.05; respectively) on CMR. A single EA patient met criteria for LVNC with a maximal NC/C ratio > 2.3. There was no statistically significant difference in NC/C ratio in the EA population (1.4 ± 0.6) vs. controls (1.1 ± 0.2), p = 0.17. There was an inverse correlation of LV ejection fraction with right ventricular end-diastolic volume and displacement index. All patients underwent the Da Silva Cone procedure at our center. Patients with preoperative LV dysfunction had longer duration of epinephrine use in the immediate postoperative period (33.7 ± 21.4 vs 10.2 ± 25.6h, p = 0.02) and longer length of hospital stay (6.3 ± 3.2 vs 4.4 ± 1.2days, p = 0.01). This is the largest study to date to evaluate preoperative LV structure and function in EA patients by CMR. In this cohort of 47 patients, preoperative LV dysfunction is fairly common and CMR has high sensitivity in detecting LV dysfunction as compared to Echo. True LV non-compaction was rare in this cohort. The presence of LV dysfunction is relevant to perioperative management and further study with larger cohorts and longer follow up are necessary.

A Case of Pregnant Woman with Severe Mitral Regurgitation Demonstrating Left Ventricular Non-compaction

A Case of Pregnant Woman with Severe Mitral Regurgitation Demonstrating Left Ventricular Non-compaction

Adverse Events in Patients With Left Ventricular Noncompaction: Risk Stratification and Treatment Options

Adverse Events in Patients With Left Ventricular Noncompaction: Risk Stratification and Treatment Options

Excessive Trabeculation of the Left Ventricle Revealed by de Novo Heart Failure in Adults: A Clinical Case with a Literature Review

Introduction: Rare cardiomyopathy left ventricle non-compaction (LVNC) or excess trabeculation is an unclassified heart disease related to the cessation of the normal process of myocardial development during the first trimester of pregnancy. Familial forms account for approximately half of the cases, and men are the most affected. The usual clinical presentation corresponds to the classic triad, which includes heart failure, arrhythmias, and thromboembolic manifestations. Case Presentation: Here, we describe the case of a 56-year-old man with no pathological history who consulted for dyspnea, and in whom transthoracic echocardiography and magnetic resonance imaging have made it possible to retain the diagnosis of an excess of trabeculations complicated by heart failure and an apical thrombus. Conclusion: LVNC is a rare cardiomyopathy that frequently affects men and is diagnosed using echocardiography and in borderline cases, supplemented by cardiac MRI.

Isolated left ventricular non-compaction: clinical characterisation of a teenage male

Isolated Left Ventricular Non-compaction (LVNC) is a type of cardiomyopathy that usually has a genetic origin. Its diagnosis is based on findings such as deep intertrabecular recesses or sinusoids and ventricular trabeculations communicating with the left ventricular cavity. LVNC was first clinically recognised almost four decades back, yet its diagnostic and management challenges persist. In this report, we present the case of an 18-year-old boy, who presented at the National Institute of Cardiovascular Diseases, Karachi, in March 2023, with complaints of dizziness, pedal oedema, and shortness of breath. Echocardiography revealed signs suggestive of LVNC, which were confirmed conclusively on Cardiovascular Magnetic Resonance (CMR) (NC/C ratio&gt;2.4). The patient underwent implantable cardioverter defibrillator (ICD) placement, was discharged after a smooth post-procedure recovery, and is doing well on follow-ups. ---Continue

Role of cardiac magnetic resonance imaging in assessing the risk of various myocardial remodeling types in left ventricular noncompaction: genetic analysis data

Aim. To analyze contrast-enhanced cardiac magnetic resonance imaging (MRI) in patients with phenotypic manifestations of left ventricular non-compaction (LVNC) and related genetic mutations, as well as to determine the relationship between mutations and types of left ventricular (LV) remodeling and with a number of other morphological and functional cardiac parameters.Material and methods. From the registry of patients with LVNC and their relatives, patients with morphological signs of LVNC and 4 related mutations (MYH7, MYBPC3, TTN, and desmin genes (DES, DSG2, DSP and DSC2)). All patients underwent contrast-enhanced cardiac MRI, based on which the type of LV remodeling was determined.Results. The study included 44 patients who, according to genetic analysis, had mutations in sarcomeric genes responsible for LVNC development. In each patient, the type of LV remodeling was determined based on cardiac MRI results. We found that if patients with LVNC have mutations in the MYBPC3 and TTN genes, the chance of LV dilatation remodeling is significantly higher. On the contrary, in the presence of a DES gene mutation, the probability of this LV remodeling is lower, and milder morphological manifestations of LVNC are noted.Conclusion. The combination of cardiac MRI data and genetic analysis improves the morphological and functional stratification of patients with LVNC.