Left Ventricular Noncompaction Patients Research Articles

Co-Phenotype of Left Ventricular Non-Compaction Cardiomyopathy and Atypical Catecholaminergic Polymorphic Ventricular Tachycardia in Association With R169Q, a Ryanodine Receptor Type 2 Missense Mutation.

Left ventricular non-compaction (LVNC) is a cardiomyopathy characterized by prominent trabeculae and intertrabecular recesses. We present the cases of 3 girls with the sameryanodine receptor type 2(RYR2) mutation who had phenotypes of both catecholaminergic polymorphic ventricular tachycardia (CPVT) and LVNC. Clinical characteristics and genetic background of the 3 patients were analyzed retrospectively. Age at onset was 5, 6, and 7 years, respectively. Clinical presentation included syncope during exercise in all 3 patients and cardiac arrest in 2 patients. LVNC diagnosis was confirmed on echocardiography according to previously defined criteria. Exercise stress testing provoked ventricular arrhythmia in two of the patients. Beta-blockers (n=3) and flecainide (n=2) were given, and an implantable cardioverter defibrillator was used in 1 patient. Genotyping identified the sameRYR2-R169Q missense mutation and no other CPVT- or LVNC-related gene mutations. Functional analysis of the mutation using HEK293 cells with single-cell Ca2+imaging and [3H]ryanodine binding analysis, indicated a gain of function: a reduced threshold for overload-induced Ca2+release from the sarcoplasmic reticulum and increased fractional Ca2+release. The rare association of LVNC and CPVT phenotypes withRYR2mutations is less likely to be coincidental. Screening for life-threatening arrhythmias using exercise or pharmacologic stress tests is recommended in LVNC patients to prevent sudden cardiac death in those with preserved LV function.

Prognostic Significance of Left Ventricular Noncompaction: Systematic Review and Meta-Analysis of Observational Studies.

Although left ventricular noncompaction (LVNC) has been associated with an increased risk of adverse cardiovascular events, the accurate incidence of cardiovascular morbidity and mortality is unknown. We, therefore, aimed to assess the incidence rate of LVNC-related cardiovascular events. We systematically searched observational studies reporting the adverse outcomes related to LVNC. The primary end point was cardiovascular mortality. We identified 28 eligible studies enrolling 2501 LVNC patients (mean age, 46 years; male/female ratio, 1.7). After a median follow-up of 2.9 years, the pooled event rate for cardiovascular mortality was 1.92 (95% CI, 1.54-2.30) per 100 person-years. LVNC patients had a similar risk of cardiovascular mortality compared with a dilated cardiomyopathy control group (odds ratio, 1.10 [95% CI, 0.18-6.67]). The incidence rates of all-cause mortality, stroke and systemic emboli, heart failure admission, cardiac transplantation, ventricular arrhythmias, and cardiac device implantation were 2.16, 1.54, 3.53, 1.24, 2.17, and 2.66, respectively, per 100 person-years. Meta-regression and subgroup analyses revealed that left ventricular ejection fraction, not the extent of left ventricular trabeculation, had an important influence on the variability of incidence rates. The risks of thromboembolism and ventricular arrhythmias in LVNC patients were similar to dilated cardiomyopathy patients. However, LVNC patients had a higher incidence of heart failure hospitalization than dilated cardiomyopathy patients. Patients with LVNC carry a similar cardiovascular risk when compared with dilated cardiomyopathy patients. Left ventricular ejection fraction-a conventional indicator of heart failure severity, not the extent of trabeculation-appears to be an important determinant of adverse outcomes in LVNC patients. Registration: https://www.crd.york.ac.uk/PROSPERO/ Unique identifier: CRD42018096313.

P1441 Predictors of systemic embolisms in a large cohort of left ventricular noncompaction patients

Abstract BACKGROUND Left ventricular noncompaction (LVNC) is associated with an increased risk of systemic embolisms (SE). However, incidence and risk factors are not well established. PURPOSE To evaluate the rate of SE in LVNC and describe risk factors. METHODS LNVC patients were included in a multicentric registry. Those with SE were considered for the analysis. RESULTS 514 patients with LVNC from 10 Spanish centres were recruited from 2000 to 2018. During a median follow-up of 4.2 years (IQR 1.9-7.1), 23 patients (4.5%) had a SE. Patients with SE (Table 1) were older at diagnosis, with no differences in gender and had similar cardiovascular risk factors. They were more frequently under oral anticoagulation (OAC). Besides, they had a more reduced LVEF, and more dilated LV and left atrium (LA). Late gadolinium enhancement (LGE) was more frequent, altogether suggesting a more severe phenotype. Patients with SE had non-significantly higher rates of hospitalization for heart failure (33% Vs 24%, p = 0.31) and atrial fibrillation (35% Vs 19%, p = 0.10). In multivariate analysis, only LA diameter was an independent predictor of SE (OR 1.04, p = 0.04). A LA diameter > 45 mm had an independent 3 fold increased risk of SE (OR 3.04, p = 0.02) (Image 1). CONCLUSIONS LVNC carries a moderate mid-term risk of SE, which appears to be irrespective of atrial fibrillation and associated with age, LV dilatation and systolic dysfunction and mainly LA dilatation. This subgroup of patients should be considered for oral anticoagulation in primary prevention. Table 1 Systemic embolisms (n = 23) No systemic embolisms (n = 491) p Men, n (%) 15 (65) 289 (56) 0.52 Median age at diagnosis (IQR) - yr 60 (48-76) 48 (30-64) 0.02 Median follow up (IQR) - yr 5.9 (3.1-7.8) 4.2 (1.8-7.1) 0.18 OAC, n (%) 19 (83) 118 (24) 0.01 LVEF (SD) - % 37 (15) 48 (17) 0.01 LVEDD (SD) - mm 58 (11) 54 (10) 0.04 LA diameter (SD) - mm 46 (9) 39 (9) 0.01 Characteristics of patients with and without systemic embolisms Abstract P1441 Figure. Image 1

Diagnostic accuracy of noncompacted-to-compacted wall ratio criteria on CMRI for the diagnosis of left ventricular noncompaction

Objectives: To investigate the diagnostic accuracy of the current criterion, noncompacted-to-compacted (NC/C) wall ratio > 2.3 oncardiac magnetic resonance imaging (CMRI) for the diagnosis of left ventricular noncompaction (LVNC).Materials and Methods: We retrospectively enrolled 37 patients as an LVNC group and a total of 97 participants with ischemic,hypertrophic, and dilated cardiomyopathy and healthy controls as a control group. The NC/C ratio was measured perpendicularlyon short-axis cine images for segments 1-16 and four-chamber cine images for the apex during the end-diastole. The sensitivity,specificity, and diagnostic accuracy of NC/C ratio > 2.3 for the diagnosis of LVNC were calculated.Results: LVNC patients comprised 24 males (64.8%) and 13 females (35.2%) with the mean age of 29.24 ± 11.79 years. The NC/C ratio> 2.3 detected in all but one of the LVNC patients (97.3%). On the other hand, the specificity of NC/C ratio > 2.3 was 79.4% for thediagnosis of the LVNC patients. Using NC/C ratio > 2.66 and > 2.8 yielded 91.9% sensitivity and 97% specificity, and 81% sensitivityand 100% specificity, respectively.Conclusion: NC/C ratio > 2.3 might lead to overdiagnosis of LVNC. We suggest using higher NC/C cut-off value in individualswithout high clinical suspicion of LVNC.

P5555Predictors of systemic embolisms in a large cohort of left ventricular noncompaction patients

Abstract Background Left ventricular noncompaction (LVNC) is associated with an increased risk of systemic embolisms (SE). However, incidence and risk factors are not well established. Purpose To evaluate the rate of SE in LVNC and describe risk factors. Methods LNVC patients were included in a multicentric registry. Those with SE were considered for the analysis. Results 514 patients with LVNC from 10 Spanish centres were recruited from 2000 to 2018. During a median follow-up of 4.2 years (IQR 1.9–7.1), 23 patients (4.5%) had a SE. Patients with SE (Table 1) were older at diagnosis, with no differences in gender and had similar cardiovascular risk factors. They were more frequently under oral anticoagulation (OAC). Besides, they had a more reduced LVEF, and more dilated LV and left atrium (LA). Late gadolinium enhancement (LGE) was more frequent, altogether suggesting a more severe phenotype. Patients with SE had non-significantly higher rates of hospitalization for heart failure (33% vs 24%, p=0.31) and atrial fibrillation (35% vs 19%, p=0.10). In multivariate analysis, only LA diameter was an independent predictor of SE (OR 1.04, p=0.04). A LA diameter>45 mm had an independent 3 fold increased risk of SE (OR 3.04, p=0.02) (Image 1). Table 1 Systemic embolisms (n=23) No systemic embolisms (n=491) p Men, n (%) 15 (65) 289 (56) 0.52 Median age at diagnosis (IQR), yr 60 (48–76) 48 (30–64) 0.02 Median follow up (IQR), yr 5.9 (3.1–7.8) 4.2 (1.8–7.1) 0.18 Hypertension, % 8 (33) 118 (24) 0.31 Diabetes mellitus, % 3 (14) 39 (8) 0.41 OAC, % 19 (83) 118 (24) 0.01 LVEF (SD), % 37 (15) 48 (17) 0.01 LVEDD (SD), mm 58 (11) 54 (10) 0.04 LVESD (SD), mm 45 (13) 38 (11) 0.01 LA diameter (SD), mm 46 (9) 39 (9) 0.01 LVEDV CMR (SD), mL 193 (75) 163 (70) 0.12 LVESV CMR (SD), mL 121 (64) 85 (64) 0.04 LGE, % 9 (40) 88 (18) 0.04 Conclusions LVNC carries a moderate mid-term risk of SE, which appears to be irrespective of atrial fibrillation and associated with age, LV dilatation and systolic dysfunction and mainly LA dilatation. This subgroup of patients should be considered for oral anticoagulation in primary prevention.

Abstract 633: Semaphorin3e-Plexind1 Signaling is Required for Cardiac Ventricular Compaction

Left ventricular noncompaction (LVNC) is one of the most common forms of genetic cardiomyopathy characterized by excessive trabeculation and impaired myocardial compaction during fetal development. LVNC patients are at higher risk to develop left or right ventricular failure, or both. While key regulators for cardiac chamber development are well studied, the role of Semaphorin-Plexin signaling in this process remains poorly understood. Here, we demonstrate that genetic deletion of Plxnd1, a class 3 semaphorin receptor in endothelial cells, leads to severe cardiac chamber defects, as characterized by excessive trabeculation and non-compaction similar to LVNC patients. Loss of Plxnd1 results in decreased expression of extracellular matrix (ECM) proteolytic genes leading to excessive deposition of cardiac jelly. We demonstrate that Plxnd1 deficiency is associated with an increase in the expression of Notch and its downstream target genes. In addition, inhibition of Notch signaling pathway can partially rescue the excessive trabeculation and non-compaction phenotype present in Plxnd1 mutants. Furthermore, we demonstrate that Semaphorin 3e (Sema3e), one of Plxnd1’s ligands is expressed in the developing heart and is required for myocardial compaction. Collectively, our results demonstrate that the Sema3e-Plxnd1 pathway is essential for myocardial trabeculation and compaction.

Comparison of echocardiographic criteria for diagnosing left ventricular noncompaction in patients with clinical cardiomyopathy

Background: Isolated noncompaction of the ventricular myocardium (INVM) is a cardiomyopathy characterized by an excessive number of prominent trabeculations with deep intertrabecular recesses in the left ventricular apex. Associated findings include systolic dysfunction, ventricular arrhythmias, and systemic emboli. Management of patients with INVM is challenging not only because of the variability in developing clinical myopathy, but also because multiple diagnostic criteria are in use. INVM remains most commonly diagnosed by echocardiography with three criteria in use. These include the criteria proposed by Lai based …

Comparison of echocardiographic criteria for diagnosing left ventricular noncompaction in patients with clinical cardiomyopathy

Comparison of echocardiographic criteria for diagnosing left ventricular noncompaction in patients with clinical cardiomyopathy

Defects in Trabecular Development Contribute to Left Ventricular Noncompaction.

Left ventricular noncompaction (LVNC) is a genetically heterogeneous disorder the etiology of which is still debated. During fetal development, trabecular cardiomyocytes contribute extensively to the working myocardium and the ventricular conduction system. The impact of developmental defects in trabecular myocardium in the etiology of LVNC has been debated. Recently we generated new mouse models of LVNC by the conditional deletion of the key cardiac transcription factor encoding gene Nkx2-5 in trabecular myocardium at critical steps of trabecular development. These conditional mutant mice recapitulate pathological features similar to those observed in LVNC patients, including a hypertrabeculated left ventricle with deep endocardial recesses, subendocardial fibrosis, conduction defects, strain defects, and progressive heart failure. After discussing recent findings describing the respective contribution of trabecular and compact myocardium during ventricular morphogenesis, this review will focus on new data reflecting the link between trabecular development and LVNC.

Circulating microRNAs as biomarkers for myocardial fibrosis in patients with left ventricular non-compaction cardiomyopathy.

IntroductionDespite the fact that cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) is a proven method for detecting myocardial fibrosis, there is a need for new and reliable serological biomarkers. Circulating miRNAs could be a practical and attractive alternative. The purpose of the study was to assess the miRNAs well established in myocardial fibrosis – miR-21, miR-29a, miR-30d and miR-133a – in the plasma of patients with left ventricular non-compaction (LVNC) that have areas of LGE assessed by CMR.Material and methodsWe prospectively enrolled 13 adult patients (9 males and 4 females; mean age: 39 ±11.7 years) considered to meet standard CMR criteria for LVNC and 10 healthy age- and sex-matched subjects. All LVNC patients and control subjects underwent CMR examination and the measurement of peripheral plasma levels of 4 miRNAs: miR-21, miR-29a, miR-30d and miR-133a.ResultsThe LGE was present in 9 of the 13 (69.2%) LVNC patients, and most often located in the ventricular septum. Compared with LGE-negative patients, LGE-positive patients had significantly lower LVEF (28.3 ±13.3% vs. 53.5 ±14.9%, p = 0.0113) and greater LV end-diastolic diameter (67.8 ±9.5 mm vs. 57 ±2.2 mm, p = 0.01). Significant up-regulation of all 4 miRNAs was observed among LGE-positive patients vs. LGE-negative patients: miR-21 (p = 0.007), miR-29a (p = 0.0001), miR-30d (p = 0.001) and miR-133a (p = 0.0003).ConclusionsThe up-regulation of miR-21, miR-29a, miR-30d and miR-133a indicates the presence of LGE in LVNC patients, and therefore they may serve as potential biomarkers for myocardial fibrosis.

Value of Cardiac Magnetic Resonance Fractal Analysis Combined With Myocardial Strain in Discriminating Isolated Left Ventricular Noncompaction and Dilated Cardiomyopathy.

Excessive trabeculation is present in isolated left ventricular noncompaction (LVNC) and dilated cardiomyopathy (DCM), which sometimes makes the differentiation between these two difficult. Fractal dimension (FD) is a unitless measure value of how completely the object fills space, which can assess the extent of myocardial trabeculae quantitatively. To compare the trabeculae features and myocardial strain derived from cardiac MR between LVNC and DCM. Respective case-control series. In all, 35 LVNC patients and 30 DCM patients were enrolled, and 20 healthy volunteers were selected as a control group. 5 T with 8-channel phased-array cardiac receiver coil including steady-state free precession cine imaging. The degree of left ventricular trabeculation was evaluated by a semiautomatic tool based on fractal analysis. Myocardial deformation was assessed by feature tracking. Independent samples Student's t-test, Mann-Whitney U-test, receiver operating characteristics (ROC) curves, and Spearman's rank coefficient were conducted. Max apical FD and mean global FD were higher in the LVNC group than in the DCM group (1.433 ± 0.074 vs. 1.341 ± 0.062, P < 0.001; 1.323 ± 0.036 vs. 1.267 ± 0.041, P < 0.001, respectively). For diagnosing LVNC, max apical FD was 1.392 (area under the curve [AUC] = 0.881, 95% confidence interval [CI]: 0.804-0.957), and the cutoff value of mean global FD was 1.283 (AUC = 0.895, 95% CI: 0.828-0.961). The global peak longitudinal strain value of the left ventricle (GPLS) showed significant differences between the LVNC group and DCM group [-6.49 (-11.41, -4.90) vs. -4.61 (-5.87, -3.61), P = 0.006]. The diagnostic accuracy for LVNC is highest when using FDs in coordination with GPLS (AUC = 0.93, 95% CI: 0.86-0.98, P < 0.001). Fractal analysis provides a quantitative measurement of myocardial trabeculation. The combination of fractal analysis with myocardial strain provides a novel biomarker in distinguishing LVNC from DCM. 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:153-163.

Abstract 17252: Left Ventricular Noncompaction in Patients With Preserved Ejection Fraction is Associated With Increased Cardiac Hospitalizations

Introduction: Prominent left ventricular trabeculations or left ventricular non-compaction (LVNC) is observed now more often with cardiac magnetic resonance imaging (MRI). The significance of LVNC in patients with preserved ejection fraction remains unknown however it may be a precursor to cardiomyopathy. Hypothesis: This study is aimed to evaluate the clinical outcome of patients with LVNC and preserved LV function compared to patients with normal myocardial anatomy and function. Methods: This is a retrospective analysis of patients referred for cardiac MRI between October 2012 and July 2017. Patients with hypertrophic cardiomyopathy, ischemic heart disease and infiltrative heart disease were excluded. Patients with prominent trabeculations and a noncompacted to compacted myocardial ratio ≥ 2.3 with a preserved left ventricular ejection fraction of ≥ 50% were included. The primary outcome is defined as cardiac hospitalizations resulting from chest pain, arrhythmias, syncope, and congestive heart failure. These patients were compared to patients who underwent cardiac MRI with preserved function and normal myocardial anatomy. Results: There were a total of 39 patients who met criteria of LVNC with preserved function by MRI. These were compared to 59 patients with preserved function and normal myocardial anatomy on MRI. There was no significant difference in demographics and LV size and function between the groups. In comparison with the control group, the LVNC group had a mean age of 44 ± 14 versus 42 ± 16, 62% female sex versus 59%, LV EF of 59 ± 5% versus 62 ± 6%, LV end diastolic volume of 148 ± 26 ml versus 146 ± 40 ml. There were a total of 7 cardiac hospitalizations, of which 5 occurred in patients with LVNC. LVNC was associated with a greater than 4-fold increased risk of events (HR4.6, 95%CI 1.0-21.8) (figure) Conclusions: In patients with preserved EF, LVNC anatomy is significantly associated with increased cardiac hospitalizations.

Abstract 16621: Holter Monitoring in Patients With Left Ventricular Noncompaction

Introduction: Multiple arrhythmias including ventricular tachycardia (VT) and atrial fibrillation (AF) have been reported in patients with left ventricular noncompaction (LVNC). We sought to determine the frequency of rhythm abnormalities on Holter monitoring, and their association with all-cause mortality, in patients with LVNC. Methods: Imaging databases from 2000-2016 were reviewed to identify patients with LVNC. On transthoracic echocardiography (TTE), LVNC was defined as: end systolic noncompacted: compacted (NC:C) ratio&gt;2 and end diastolic epicardium to trough: epicardium to peak trabeculation (X:Y) ratio&lt;0.5. Holter monitor reports from the medical record were evaluated. VT was defined as ≥3 consecutive beats of ventricular origin. All-cause mortality was obtained from a web-based research and location service (Accurint). We used a proportional hazards model to determine associations of Holter variables with all-cause mortality. Results: Among 340 LVNC patients, Holter reports were available for 177 patients (median age 45 years, interquartile range [IQR] 33-61; 45% females). On TTE, the median NC:C ratio was 2.7 (IQR 2.4-3.2) and X:Y ratio was 0.25 (IQR 0.20-0.28). The median ejection fraction (EF) was 48% (IQR 33-58). 48 patients (27%) had at least one episode of VT (median 4 episodes, IQR 2-4). The median longest duration of VT was 5 beats (IQR 4-9) and maximum rate was 148 beats per minute (IQR: 125-169). PVC burden &gt;5% and 20% was present in 13% and 5% of patients respectively. Patients with EF&lt;50% were more likely to have VT (43% vs 16%, p=0.0003) and PVC burden &gt;5% (19% vs 7%, p=0.03). AF was infrequent (N=5, all persistent). All-cause mortality was 12% over median 6.9 years of follow up (IQR: 3.6-11.3 years). Presence of VT and PVC burden on Holter monitoring were not associated with all-cause mortality (p&gt;0.05). Among patients with VT, the number, longest duration, and fastest rate of VT episodes were not associated with all-cause mortality. Conclusions: Ventricular tachycardia on Holter monitoring is common among patients with LVNC, especially those with a reduced EF. However, the clinical significance of this finding is uncertain, and presence of VT was not associated with long term all-cause mortality.

Clinical and Echocardiographic Impact of Tafazzin Variants on Dilated Cardiomyopathy Phenotype in Left Ventricular Non-Compaction Patients in Early Infancy.

Left ventricular non-compaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium and numerous prominent trabeculations, and is often associated with dilated cardiomyopathy (DCM). Variants in the gene encoding tafazzin (TAZ) may change mitochondrial function and cause dysfunction of many organs, but they also contribute to the DCM phenotype in LVNC, and the clinical and echocardiographic features of children with this phenotype are poorly understood. Methods and Results: We enrolled 92 DCM phenotype LVNC patients and performed next-generation sequencing to identify the genetic etiology. Ten TAZ variants were identified in 15 male patients (16.3%) of the 92 patients, including 3 novel missense substitutions. The patients with TAZ variants had a higher frequency of early onset of disease (92.3% vs. 62.3%, P=0.0182), positive family history (73.3% vs. 20.8%, P=0.0001), and higher LV posterior wall thickness Z-score (8.55±2.60 vs. 5.81±2.56, P=0.0103) than those without TAZ variants, although the mortality of both groups was similar. This study provides new insight into the impact of DCM phenotype LVNC and emphasizes the clinical advantages available for LVNC patients with TAZ variants.

Left ventricular noncompaction in patients with coronary artery disease: Preliminary analysis of echocardiographic findings

We retrospectively analyzed the echocardiographic findings of eight patients with left ventricular noncompaction (LVNC) and concurrent coronary artery disease. This study was conducted in Yijishan Hospital between January 2012 and May 2017. Of the eight patients, six were diagnosed with coronary arterial atherosclerosis, one patient with coronary pulmonary fistula, and one with coronary myocardial bridge. Regional wall motion abnormalities were detected in all patients. Echocardiography can provide significant information about LVNC in patients with coronary artery disease. However, whether regional wall motion abnormalities are caused by coronary artery disease or noncompaction of the myocardium remains unknown in most patients.

Prevalence and Prognostic Significance of Left Ventricular Noncompaction in Patients Referred for Cardiac Magnetic Resonance Imaging.

Presence of prominent left ventricular trabeculation satisfying criteria for left ventricular noncompaction (LVNC) on routine cardiac magnetic resonance examination is frequently encountered; however, the clinical and prognostic significance of these findings remain elusive. This registry aimed to assess LVNC prevalence by 4 current criteria and to prospectively evaluate an association between diagnosis of LVNC by these criteria and adverse events. There were 700 patients referred for cardiac magnetic resonance: 42% were women, median age was 70 years (range, 45-71 years), mean left ventricular ejection fraction was 51% (±17%), and 32% had late gadolinium enhancement on cardiac magnetic resonance. The cohort underwent diagnostic assessment for LVNC by 4 separate imaging criteria-referenced by their authors as Petersen, Stacey, Jacquier, and Captur, with LVNC prevalence of 39%, 23%, 25% and 3%, respectively. Primary clinical outcome was combined end point of time to death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, and heart failure hospitalization. Secondary clinical outcomes were (1) all-cause mortality and (2) time to the first occurrence of any of the following events: cardiac death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, or heart failure hospitalization. During a median follow-up of 7 years, there were no statistically significant differences in assessed outcomes noted between patients with and without LVNC irrespective of the applied criteria. Current criteria for the diagnosis of LVNC leads to highly variable disease prevalence in patients referred for cardiac magnetic resonance. The diagnosis of LVNC, by any current criteria, was not associated with adverse clinical events on nearly 7 years of follow-up. Limited conclusions can be made for Captur criteria due to low observed prevalence.

Prolonged QTc indicates the clinical severity and poor prognosis in patients with isolated left ventricular non-compaction.

Isolated left ventricular non-compaction (LVNC) is a rare cardiomyopathy that leads to severe clinical complications. This study is to investigate whether or not prolonged QTc is a good indicator for evaluating the severity of fibrosis and predicting the prognosis of LVNC, and if native T1 can be used to quantify the fibrosis. 32 LVNC patients and 14 healthy controls with matched age and sex were examined by CMR and ECG to acquire native T1, QTc interval, and ECG abnormalities. 18 LVNC patients had normal QTc and 14 LVNC patients had prolonged QTc. The mean native T1 value of the normal controls, normal QTc and prolonged QTc patients was 1096.0 ± 41.5, 1141.98 ± 45.46, and 1182.67 ± 42.02ms, respectively. One-way ANVOA showed significant differences in native T1 among three groups (F = 14.9, p < 0.001). In LVNC patients, the QTc interval significantly correlated with LVEF (p = 0.003, r = 0.51) and native T1 values (p = 0.015, R = -0.47). This suggests that prolonged QTc is associated with more severe compacted myocardial fibrosis, more cardiac dysfunction, and a poorer prognosis in LVNC patients. Follow-up data showed significant differences in adverse events between patients with normal QTc and patients with prolonged QTc (p = 0.036). Prolonged QTc interval leads to more severe compacted myocardial fibrosis, poorer cardiac dysfunction, and poorer prognosis in LVNC patients.

IPSC-derived cardiomyocytes reveal abnormal TGF-β signalling in left ventricular non-compaction cardiomyopathy.

Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and its pathogenesis has been associated with the developmental defect of the embryonic myocardium. We show that patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from LVNC patients carrying a mutation in the cardiac transcription factor TBX20 recapitulate a key aspect of the pathological phenotype at the single-cell level and was associated with perturbed transforming growth factor beta (TGFβ) signaling. LVNC iPSC-CMs have decreased proliferative capacity due to abnormal activation of TGFβ signaling. TBX20 regulates the expression of TGFβ signaling modifiers including a known genetic cause of LVNC, PRDM16, and genome editing of PRDM16 caused proliferation defects in iPSC-CMs. Inhibition of TGFβ signaling and genome correction of the TBX20 mutation were sufficient to reverse the disease phenotype. Our study demonstrates that iPSC-CMs are a useful tool for the exploration of pathological mechanisms underlying poorly understood cardiomyopathies including LVNC.

Usefulness of speckle myocardial imaging modalities for differential diagnosis of left ventricular non-compaction of the myocardium

Background/objectivesCurrent diagnostic criteria for left ventricular non-compaction (LVNC) may result in over-diagnosis of the disease. We evaluate the role of speckle imaging in differential diagnosis of LVNC. Methods and resultsWe included all patients who, between January 2012 and May 2015, fulfilled currently accepted criteria for LVNC (28 patients). A control group of 28 healthy individuals and a third group of 13 patients with dilated cardiomyopathy (DCM) were created. Speckle-tracking echocardiography was performed in all groups. Thirteen patients with LVNC had an ejection fraction (EF) <50% (33.5%, SD 10). When compared to controls, patients with LVNC and EF<50% had a larger LV, larger left atrial diameter (LA), reduced e′, and reduced global longitudinal strain (GLS). All but one patient with LVNC and EF<50% showed an abnormal LV rotation. This abnormal pattern was observed in 4 LVNC patients (27%) with EF≥50% and in none of the controls. In patients with LVNC, EF ≥50%, and abnormal rotation, GLS was lower than in controls, (−17 (SD 3) vs −21 (SD 3)). Rigid body rotation (RBR) was also observed in 2 DCM patients, with significant differences in EF, GLS, LV diameters relative to the rest of the DCM group. ConclusionsIn patients who fulfil the morphologic criteria for LVNC, speckle myocardial imaging techniques could be useful in differentiating between healthy individuals (functionally normal LV) and patients with LVNC (with functional abnormalities in the myocardium in spite of a preserved EF).

The role of cardiac computed tomography in diagnosing left ventricular noncompaction in patients with sinus node dysfunction

The role of cardiac computed tomography in diagnosing left ventricular noncompaction in patients with sinus node dysfunction