Search Results (95)

Cardiac MRI (CMR) is the gold standard for diagnosing left ventricular excessive trabeculation (LVET), whereas echocardiography (Echo) often does not yield a definitive diagnosis. The use of ultrasound contrast material offers the potential for more accurate imaging of the trabecular system; however, we do not yet have diagnostic criteria developed specifically for contrast Echo (CE-Echo). We aimed to determine the role of CE-Echo in the diagnosis of LVET and to propose a novel method for quantifying trabeculation. We included 55 LVET subjects and 54 age- and sex-matched healthy Control subjects. All subjects underwent non-contrast Echo, CE-Echo, and CMR examinations. In addition to volumetric parameters and ejection fraction (EF), we measured the area of the trabeculated layer and its ratio to the LV area (Trab/LV_area) on apical CE-Echo views. Based on the CMR-derived diagnosis, the Trab/LV_area ratio identified individuals with LVET with high specificity (98%) and sensitivity (95%) when the average of the apical views reached 17% (AUC = 0.98), or when it exceeded 20% in at least one view (AUC = 0.96). The use of CE-Echo may assist in the quantitative diagnosis of LVET in addition to its morphological assessment, and the Trab_area/LVarea may be a good additional criterion in the diagnosis of LVET. Full article

Left-ventricular non-compaction (LVNC) is a recently classified cardiomyopathy that involves abnormal trabeculations inside the left ventricle, most commonly located in the ventricular apex. There are 9 distinct types of non-compaction cardiomyopathy that can impact both the left and right ventricles with subtypes involving mostly pediatric patients with concurrent congenital heart disease (CHD), to individuals in late adult-staged ages. LVNC affects the population with an estimated range of incidence from 0.014% to 1.3% and the disease can be diagnosed with the utilization of imaging studies such as transthoracic echocardiography (TTE). LVNC can also impact and lead patients to develop heart failure with estimated prevalence that can reach to 3–4% during their lifetime. LVNC often leads to complications such as heart failure, arrhythmias, and thromboembolic events and without adequate medical management and pharmacological therapies this can progress and lead to worsening cardiac function, sudden cardiac arrest, and even death. There are no strict guidelines organized for screening and monitoring for LVNC in patients except with the inclusion of having a high suspicion in patients without other cardiac abnormalities. Thus, more advanced clinical research and the establishment of diagnostic protocols needs to be standardized in order to further investigate the causes, prognostic factors and therapeutic modalities of patients with LVNC. The field of LVNC cardiomyopathy is expanding but better understanding of the pathophysiology and genetic influence of this cardiac disease is vital for the precision treatment and personalized care of LVNC. Full article

Left ventricular noncompaction cardiomyopathy (LVNC) is characterised by a two-layered ventricular wall with prominent trabeculations and deep recesses adjacent to a thinned compact layer. The phenotype spans from incidental findings to severe heart failure and malignant arrhythmias. More than 190 genes belonging to sarcomeric, cytoskeletal, mitochondrial, transcriptional and signalling pathways have been implicated, although only a subset reaches high gene disease validity in contemporary frameworks. Objectives: (i) Delineate the validated genetic landscape of LVNC; (ii) integrate developmental biology with cardiac genomics; (iii) translate genotype knowledge into diagnostic, prognostic and therapeutic guidance; (iv) outline a research agenda for precision cardiology. Methods: A narrative, pathway-oriented review of human and experimental studies (2000–July 2024). Results: Thirty-two genes meet definitive/strong validity thresholds and cluster in five biological networks. Oligogenic constellations account for ~4% of probands in recent cohorts. Imaging correlates (especially quantitative trabecular complexity and diffuse fibrosis metrics) provide complementary risk information. Conclusions: LVNC represents a convergence phenotype triggered by perturbations across developmental and structural networks; clinical management benefits from integrated genomics–imaging workflows and mechanism-informed trial design. Full article

Left ventricular (LV) apical obliteration represents a convergent imaging phenotype arising from diverse cardiac conditions, including thrombotic, hypertrophic, infiltrative, congenital, and neoplastic diseases. These conditions, despite sharing overlapping morphological features, require profoundly different management strategies. In this context, an accurate characterization of the LV apex is a cornerstone point, and can be performed through various techniques. Advances in multimodality imaging have substantially improved diagnostic precision, allowing clinicians to differentiate true obliteration from mimicking conditions such as hypertrabeculation, apical hypertrophy, or subendocardial fibrosis. This review provides a comprehensive overview of the anatomical variability of the LV apex and its implications for imaging interpretation. We appraise the role of echocardiography, including contrast-enhanced and speckle-tracking studies—alongside cardiac magnetic resonance (CMR), computed tomography (CT), and selective nuclear imaging in the evaluation of apical pathology. For each principal cause of apical obliteration—LV thrombus, apical hypertrophic cardiomyopathy, left ventricular non-compaction, endomyocardial fibrosis, cardiac amyloidosis, and intracardiac tumors—we outline key diagnostic clues, imaging red flags, and distinguishing tissue characteristics. Special emphasis is given to the incremental value of CMR for tissue characterization, thrombus detection, and fibrosis mapping, as well as to the interpretative challenges posed by apical foreshortening, near-field artefacts, and suboptimal acoustic windows. A practical, stepwise imaging framework is proposed to guide clinicians through the differential diagnosis of apical obliteration using an integrated multimodality approach. Future directions include the incorporation of 4D flow, advanced mapping techniques, and artificial intelligence-powered analysis to refine apical phenotyping and identify early disease signatures. Recognizing the full spectrum of apical pathology and its imaging manifestations is essential to prevent misdiagnosis, enable timely therapeutic decisions, and improve risk stratification. Full article

This study investigates FLNC mutations in Chinese cardiomyopathy patients. Background: Inherited cardiomyopathies, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) are major heart failure causes. FLNC, critical for muscle structure, is implicated in myofibrillar myopathy and isolated DCM (3–4% cases) with ventricular arrhythmias. Missense variants are linked to HCM and protein aggregation. A cohort of 25 patients with pathogenic/likely pathogenic FLNC mutations (2022–2025, Beijing Anzhen Hospital) underwent whole-exome sequencing (WES) using IDT kit 1.0/Hiseq 4000. Variants were classified via the American College of Medical Genetics and Genomics (ACMG) guidelines. Clinical data (echocardiography, CMR, labs) and follow-up data (prognosis, meds, and family history) were collected. The statistics used SPSS (p < 0.05). The mean age was 38 ± 14.6 years (13 males). There were 25 FLNC mutations: 12 single nucleotide polymorphisms (SNPs), 5 deletions, 2 duplications, and 3 deletion-insertions, classified as 6 pathogenic, 16 likely pathogenic, and 3 variants of uncertain significance (VUS). Diagnoses: 24% dilated cardiomyopathy (DCM), 8% hypertrophic cardiomyopathy (HCM), and 4% left ventricular non-compaction. Nonsense mutation carriers exhibited significantly higher tricuspid regurgitation prevalence compared to frameshift mutation carriers (6/9 vs. 2/10; p = 0.04). Echocardiography revealed reduced left ventricular ejection fraction (LVEF) (41.5 ± 14.1%), with statistically significant differences in fractional shortening (p = 0.024) and aortic root diameter (p = 0.028). Pedigree analysis confirmed that a frameshift mutation (LP) co-segregated with familial DCM and was associated with severe phenotypes, including sudden cardiac death. Furthermore, nonsense FLNC mutations correlated with increased tricuspid regurgitation severity, smaller aortic root dimensions, and reduced pulmonary artery flow velocity. Full article

Background: Cardiomyopathies are a heterogeneous group of heart muscle disorders with diverse genetic origins. Biallelic loss-of-function (LoF) variants in the nebulin-related anchoring protein (NRAP) gene have been linked to dilated cardiomyopathy (DCM) and left ventricular noncompaction cardiomyopathy, though only a few families have been described. NRAP, a member of the Nebulin family, plays a key role in cardiomyocyte development, structural integrity, and muscle function. Methods: We investigated two Italian siblings with DCM born to consanguineous parents from a small village in Campania. Exome sequencing, homozygosity mapping, and comparative analyses with other reported cases were performed. Genealogical research was conducted using civil registry data to reconstruct extended family pedigrees. Results: Both siblings were homozygous for a LoF variant in NRAP (NM_198060.4:c.619del; p.Val207TrpfsTer20). A third brother with tachycardia-induced cardiomyopathy, as well as their living mother, who did not have cardiac abnormalities, were found to be heterozygous. The same homozygous variant was recently identified in another Italian family with DCM coming from North-eastern Italy, whose proband also originated from a nearby village in Campania. These two families exhibited heterogeneity in clinical presentation. Homozygosity analysis revealed a >25 Mb shared region on chromosome 10 encompassing NRAP, supporting a common ancestral origin. While genealogical reconstruction did not allow identification of a shared ancestor, it confirmed consanguinity and enabled the recognition of potential carriers across both families. Conclusions: Our findings strengthen the evidence for NRAP as a disease-causing gene in cardiomyopathies and highlight a likely founder effect in Campania. Incorporating NRAP into genetic testing panels is warranted, especially in populations with high rates of consanguinity or suspected founder variants. Full article

Background/Objectives: Sodium glucose co-transporter 2 inhibitors (SGLT2is) improve outcomes in heart failure; however, data in left ventricular non-compaction cardiomyopathy (LVNC) patients are limited. We sought to analyze the clinical effects of the SGLT2is dapagliflozin and empagliflozin in patients with LVNC. Methods: Thirty consecutive LVNC patients diagnosed by CMR were prospectively enrolled. Clinical, biochemical and echocardiography data were obtained at the initiation of the SGLT2is and at the 12-month follow-up. All patients were on stable guideline-directed medical therapy. A response to SGLT2i therapy was defined as an improvement in LVEF ≥ 5% at 12 months. Results: Of the 30 enrolled patients, 25 were male, with a mean age of 49 ± 16 years and few comorbidities. Dapagliflozin 10 mg was prescribed to 23 patients and empagliflozin 10 mg to 7 patients. Five patients experiened an adverse event during follow-up (one sudden cardiac death; four heart transplantations or LVAD implantations). During follow-up, significant improvements were observed in LVEF (32.1 ± 6.9% vs. 43.5 ± 9.7%; p = 0.003), LVOT VTI (14.8 ± 6.5 cm vs. 17.6 ± 3.3 cm; p = 0.008), E/e′ (14.8 ± 4.7 vs. 10.0 ± 4.1; p < 0.001), and TAPSE (2.0 ± 0.4 cm vs. 2.3 ± 0.4 cm; p = 0.012). NT-proBNP levels decreased significantly (2025 ± 2198 pg/mL vs. 582 ± 803 pg/mL; p = 0.005). Eighteen patients responded favorably to SGLT2i therapy (Group A), whereas seven showed no significant LVEF improvement (Group B). The groups did not differ significantly in age, sex, baseline creatinine, or bilirubin. Compared to Group B, Group A had a smaller baseline LV end-diastolic diameter (6.3 ± 0.8 cm vs. 7.1 ± 0.9 cm; p = 0.025) and lower NT-proBNP levels (1720 ± 1662 pg/mL vs. 4527 ± 4397 pg/mL; p = 0.02). Conclusions: In patients with LVNC, SGLT2i therapy is associated with significant reverse remodeling and functional improvement. Benefits may be greater in those with less advanced disease. Full article

Introduction: Changes in left ventricular (LV) wall thickness serve as important diagnostic and prognostic indicators in various cardiovascular diseases. To date, no automated software exists for the measurement of myocardial segmental wall thickness in cardiac MRI (CMR), which leads to reliance on manual caliper measurements that carry risks of inaccuracy. Aims: This paper aims to present a new automated segmental wall thickness measurement software, OptiLayer, developed to address this issue and to compare it with the conventional manual measurement method. Methods: In our pilot study, the algorithm of the OptiLayer software was tested on 50 HEALTHY individuals, and 50 excessively trabeculated noncompaction (LVET) subjects with preserved LV function, whose morphology makes it more challenging to measure left ventricular wall thickness, although often occurring with myocardial thinning. Measurements were performed by two independent investigators who assessed LV wall thicknesses in 16 segments, both manually using the Medis Suite QMass program and automatically with the new OptiLayer method, which enables high-density sampling across the distance between the epicardial and endocardial contours. Results: The results showed that the segmental wall thickness measurement values of the OptiLayer algorithm were significantly higher than those of the manual caliper. In comparisons of the HEALTHY and LVET subgroups, OptiLayer measurements demonstrated differences at several points than manual measurements. Between the investigators, manual measurements showed low intraclass correlations (ICC below 0.6 on average), while measurements with OptiLayer gave excellent agreement (ICC above 0.9 in 75% of segments). Conclusions: Our study suggests that OptiLayer, a new automated wall thickness measurement software based on high-precision anatomical segmentation, offers a faster, more accurate, and more reproducible alternative to manual measurements. Full article

Left ventricular non-compaction cardiomyopathy (LVNC) is an uncommon myocardial phenotype characterized by prominent trabeculae and deep blood-filled recesses. The expanding use of cardiac magnetic resonance (CMR) has increased detection, yet uncertainty persists about whether LVNC is a distinct disease or a phenotype that overlaps with other cardiomyopathies. LVNC expression reflects the interplay among genotype, sex, ancestry, and hemodynamic load and thus serves as a model for precision cardiology. We conducted a narrative review of literature published between January 2000 and April 2025 in major databases. We included clinical studies with at least 10 patients, meta-analyses, reviews, and consensus statements addressing pathophysiology, genetics, diagnosis, prognosis, and treatment. Sarcomeric variants account for a substantial fraction of cases and connect LVNC with dilated and hypertrophic cardiomyopathies. Echocardiographic and CMR criteria identify the phenotype but blur the boundary between physiological and pathological hypertrabeculation. Fibrosis on late gadolinium enhancement and systolic dysfunction are consistently associated with worse outcomes. Current management largely adapts heart-failure strategies, including neurohormonal blockade, SGLT2 inhibitors, and implantable cardioverter-defibrillators in selected high-risk patients. Optimal care integrates clinical, imaging, and genetic information. The lack of universal diagnostic criteria highlights the need for prospective studies and consensus to standardize diagnosis and treatment. Future algorithms that combine multi-omics, quantitative imaging, and AI-based risk prediction could individualize surveillance, pharmacotherapy, and device therapy. Full article

Background: Ebstein’s anomaly (EA) is a rare congenital heart defect characterized by failure of tricuspid valve delamination during embryogenesis. Left ventricular (LV) hypertrabeculation results from incomplete myocardial compaction during fetal development. EA is associated with LV hypertrabeculation in 0.14% of cases, and EA is the most common congenital heart disease in LV hypertrabeculation (up to 29%), suggesting a shared embryogenetic pathway. Case Report: We describe a female patient prenatally diagnosed with EA and a large ventricular septal defect. Postnatal echocardiography confirmed EA with moderate regurgitation and revealed previously unnoticed left ventricular excessive trabeculations. Whole exome sequencing revealed a heterozygous never-described variant of unknown significance in the TNNC1 gene. Discussion: The genetic link between EA and LV hypertrabeculation remains unclear, though variants in sarcomeric or cytoskeletal genes like MYH7, TPM1, and NKX2.5—essential for cardiac development—have been implicated. A developmental hypothesis suggests that aberrant contraction during endocardial-to-mesenchymal and epicardial-to-mesenchymal transformation (5th–8th gestational weeks) may affect valve delamination and ventricular compaction via parallel signaling pathways. TNNC1 encodes troponin C1, a subunit of the troponin complex involved in muscle contraction. Its mutations are known to alter calcium sensitivity and impair cardiac contractility. Conclusions: EA and LV hypertrabeculation patients diagnosed in infancy have a greater risk of negative outcomes. Early, especially prenatal, diagnosis is crucial. Genetic analysis can provide fundamental insight into cardiac development. This new and rare variant of TNNC1 gene supports the hypothesis that early cardiomyocytes dysfunction disrupts both valve delamination and left ventricular compaction and that the two diseases share a common genetic pathway related to cardiomyocyte contraction. Full article

Background: Left ventricular (LV) non-compaction (NC) is a rare ventricular phenotype characterized by a thin compacted epicardial layer and an extensive non-compacted endocardial layer with prominent LV trabeculations and deep intertrabecular recesses. According to the recent literature, no information is available regarding the abnormalities of the aortic valve annulus (AVA) in LVNC. Therefore, the aim of the present study was to perform a detailed analysis of the AVA by three-dimensional speckle-tracking echocardiography (3DSTE) in LVNC patients and to compare the findings with matched healthy controls. Methods: The present study comprised 21 isolated LVNC patients, from which 9 cases were excluded due to inferior image quality. The remaining group consisted of 12 patients with isolated LVNC (mean age: 54.6 ± 13.6 years, 7 males). Jenni’s echocardiography criteria served as a definition of LVNC. The 12 patients’ results were compared to 38 healthy age- and gender-matched controls (mean age: 48.2 ± 8.0 years, 19 males). Subgroups of patients having a greater end-diastolic versus end-systolic AVA area were also compared. Results: Most of AVA dimensions did not differ significantly between LVNC patients and controls; however, most LVNC patients showed a larger end-diastolic AVA area (9 out of 12, 75%), which was a significantly larger ratio as seen in matched controls (11 out of 38, 29%, p < 0.05). Aortic valve annular plane systolic excursion (AAPSE) proved to be significantly reduced in all LVNC patients (1.12 ± 0.24 cm vs. 0.78 ± 0.28 cm, p < 0.05) and in LVNC subjects with a greater end-diastolic AVA area (1.11 ± 0.21 cm vs. 0.72 ± 0.21 cm, p < 0.05). Basal LV radial (RS) and longitudinal (LS) strains were reduced in healthy adults with a greater end-diastolic AVA area as compared to cases with a greater end-systolic AVA area. In LVNC, not only basal LV-RS and LV-LS, but also LV circumferential strain (CS) proved to be reduced regardless of whether the AVA was greater in end-diastole or in end-systole. Conclusions: In patients with isolated LVNC, the AVA is not dilated; however, the presence of a greater end-diastolic AVA area is observed more frequently than in healthy controls. AAPSE and basal LV-RS, LV-LS and LV-CS values are significantly reduced in LVNC irrespective of whether the end-systolic or end-diastolic AVA area is greater. Full article

Abnormal aortic elasticity serves as a marker for cardiovascular mortality and has a negative impact on the left ventricular (LV) afterload. Noncompaction cardiomyopathy (NCCM) is characterized by hypertrabeculation of the LV endomyocardial wall, with an underdeveloped endocardial helix. This may result in absence of LV twist, disturbed aortic elasticity, LV dysfunction, and ultimately premature heart failure (HF). This study compared the aortic stiffness and clinical outcome in patients with NCCM to that of a control group with dilated cardiomyopathy (DCM). Sixty NCCM patients, matched by age and sex, were compared with 60 DCM controls. Transthoracic echocardiography was performed to measure the systolic (SD) and diastolic diameters (DD) of the ascending aorta. These measurements, along with systolic (SBP) and diastolic blood pressure (DBP), were utilized to calculate the aortic stiffness index defined as ln(SBP/DBP)/[(SD-DD)/DD]. This index was then compared to clinical features and outcome. The mean age was 49 ± 16 years (55% males) in the NCCM group and 49 ± 16 years (55% male) in the DCM group. Aortic stiffness index (ASI) was significantly higher in the NCCM group than in the DCM group (7.0 [5.8–10.2] vs. 6.2 [4.8–7.7], p = 0.011). This difference remained statistically significant after adjustment for established risk factors associated with aortic stiffness (β = 1.771; 95% CI [0.253–3.289], p = 0.023). Patients with NCCM demonstrated increased aortic stiffness when compared to those with DCM, which may reflect the underlying pathophysiological processes. Additional research is necessary to evaluate the impact of aortic stiffness on the advancement of LV dysfunction, the onset of heart failure, and long-term outcomes. Full article

Background: Left ventricular non-compaction cardiomyopathy (LVNC) is a congenital heart disease characterized by abnormal prenatal development of the left ventricle that has an aberrantly thick trabecular layer and a thinner compacted myocardial layer. However, the underlying molecular mechanisms of LVNC regulated by mitochondrial phosphatase genes remain largely unresolved. Methods: We generated a mouse model with cardiac-specific deletion (CKO) of Ptpmt1, a type of mitochondrial phosphatase gene, using the αMHC-Cre, and investigated the effects of cardiac-specific Ptpmt1 deficiency on cardiac development. Morphological, histological, and immunofluorescent analyses were conducted in Ptpmt1 CKO and littermate controls. A transcriptional atlas was identified by RNA sequencing (RNA-seq) analysis. Results: We found that CKO mice were born at the Mendelian ratio with normal body weights. However, most of the CKO mice died within 24 h after birth, developing spontaneous ventricular tachycardia. Morphological and histological analysis further revealed that newborn CKO mice developed an LVNC phenotype, evidenced by a thicker trabecular layer and a thinner myocardium layer, when compared with the littermate control. We then examined the embryonic hearts and found that such an LVNC phenotype could also be observed in CKO hearts at E15.5 but not at E13.5. We also performed the EdU incorporation assay and demonstrated that cardiac cell proliferation in both myocardium and trabecular layers was significantly reduced in CKO hearts at E15.5, which is also consistent with the dysregulation of genes associated with heart development and cardiomyocyte proliferation in CKO hearts at the same stage, as revealed by both the transcriptome analysis and the quantitative real-time PCR. Deletion of Ptpmt1 in mouse cardiomyocytes also induced an increase in phosphorylated eIF2α and ATF4 levels, indicating a mitochondrial stress response in CKO hearts. Conclusions: Our results demonstrated that Ptpmt1 may play an essential role in regulating left ventricular compaction during mouse heart development. Full article

Ventricular chamber development involves the coordinated maturation of diverse cardiomyocyte cell populations. In the human fetal heart, single-cell and single-nucleus RNA sequencing technologies and spatial transcriptomics reveal marked regional gene expression differences. In contrast, the mouse ventricular wall appears more homogeneous, except for a transient hybrid cardiomyocyte population co-expressing compact (Hey2) and trabecular (Irx3, Nppa, Bmp10) markers, indicating a transitional lineage state. To further investigate this, we used in situ hybridization (ISH) to examine the expression of a selected set of cardiomyocyte markers in normal and left ventricular non-compaction cardiomyopathy (LVNC) mouse models. In developing mouse ventricles, the expression of key marker genes was largely restricted to two wide myocardial domains, compact and trabecular myocardium, suggesting a less complex regional organization than the human fetal heart. Other markers labeled endocardial and coronary endothelial cells rather than cardiomyocytes, differing from patterns observed in the human heart. In the LVNC model, various markers exhibited altered spatial expression, indicating that the precise regional organization of gene expression is critical for normal ventricular wall maturation. These findings underscore the critical role of spatially regulated gene programs in ventricular chamber development and point to their potential involvement in cardiomyopathy pathogenesis. Full article

Left ventricular noncompaction (LVNC) is characterized by excessive trabeculation, which may impair left ventricular function over time. While cardiac magnetic resonance imaging (CMR) is considered the gold standard for evaluating LV morphology, the optimal modality for follow-up remains uncertain. This study aimed to assess the correlation and agreement among two-dimensional transthoracic echocardiography (2D_TTE), three-dimensional transthoracic echocardiography (3D_TTE), and CMR by comparing volumetric and strain parameters in LVNC patients and healthy individuals. Thirty-eight LVNC subjects with preserved ejection fraction and thirty-four healthy controls underwent all three imaging modalities. Indexed end-diastolic, end-systolic, and stroke volumes, ejection fraction, and global longitudinal and circumferential strains were evaluated using Pearson correlation and Bland–Altman analysis. In the healthy group, volumetric parameters showed strong correlation and good agreement across modalities, particularly between 3D_TTE and CMR. In contrast, agreement in the LVNC group was moderate, with lower correlation and higher percentage errors, especially for strain parameters. Functional data exhibited weak or no correlation, regardless of group. These findings suggest that while echocardiography may be suitable for volumetric follow-up in LVNC after baseline CMR, deformation parameters are not interchangeable between modalities, likely due to trabecular interference. Further studies are warranted to validate modality-specific strain assessment in hypertrabeculated hearts. Full article