Ventricular Noncompaction Cardiomyopathy Research Articles

COQ7 defect causes prenatal onset of mitochondrial CoQ10 deficiency with cardiomyopathy and gastrointestinal obstruction.

COQ7 pathogenetic variants cause primary CoQ10 deficiency and a clinical phenotype of encephalopathy, peripheral neuropathy, or multisystemic disorder. Early diagnosis is essential for promptly starting CoQ10 supplementation. Here, we report novel compound heterozygous variants in the COQ7 gene responsible for a prenatal onset (20 weeks of gestation) of hypertrophic cardiomyopathy and intestinal dysmotility in a Bangladesh consanguineous family with two affected siblings. The main clinical findings were dysmorphisms, recurrent intestinal occlusions that required ileostomy, left ventricular non-compaction cardiomyopathy, ascending aorta dilation, arterial hypertension, renal dysfunction, diffuse skin desquamation, axial hypotonia, neurodevelopmental delay, and growth retardation. Exome sequencing revealed compound heterozygous rare variants in the COQ7 gene, c.613_617delGCCGGinsCAT (p.Ala205HisfsTer48) and c.403A>G (p.Met135Val). In silico analysis and functional in vitro studies confirmed the pathogenicity of the variants responsible for abolished activities of complexes I + III and II + III in muscle homogenate, severe decrease of CoQ10 levels, and reduced basal and maximal respiration in patients' fibroblasts. The first proband deceased at 14 months of age, whereas supplementation with a high dose of CoQ10 (30 mg/kg/day) since the first days of life modified the clinical course in the second child, showing a recovery of milestones acquirement at the last follow-up (18 months of age). Our study expands the clinical spectrum of primary CoQ10 deficiency due to COQ7 gene defects and highlights the essential role of multidisciplinary and combined approaches for a timely diagnosis.

[Analysis of long-term prognosis and risk factors in patients with dilated cardiomyopathy].

Objective: To investigate the risk factors and long-term prognosis of major adverse cardiovascular events(MACEs) in patients with dilated cardiomyopathy (DCM). Methods: This study was a single-center retrospective cohort study. Clinical information from 300 patients with DCM hospitalized in Peking Union Medical College Hospital from April 2013 to April 2023 was collected. Based on echocardiography results, the patients were divided into two groups: isolated DCM and DCM with left ventricular non-compaction cardiomyopathy (LVNC). The MACEs, including major heart failure events, severe ventricular arrhythmias, and cardiovascular death, were recorded by outpatient or telephone follow-up. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the prognosis of patients with DCM. Kaplan-Meier curve and log-rank were used for survival analysis to compare the difference in the incidence of cardiovascular events between the two groups. Results: The included 300 DCM patients were (47.8±16.8) years old, with 197 males (65.7%), of which 237 (79.0%) were isolated DCM and 63 (21.0%) were DCM with LVNC. The follow-up time was 4.0 (1.9, 6.2) years. A total of 142 (47.3%) MACEs occurred, including 117 (39.0%) major heart failure events, 20 (6.7%) severe ventricular arrhythmia events, and 53 (17.7%) cardiovascular death events. Multivariate Cox proportional hazard regression analysis showed that increased left ventricular end-diastolic diameter (HR=1.21, 95%CI: 1.01-1.44, P=0.042), moderate or severe mitral regurgitation (HR=1.71, 95%CI: 1.19-2.47, P=0.004), increased ln (N-terminal pro-B-type natriuretic peptide) (HR=1.30, 95%CI: 1.10-1.54, P=0.002) were independent risk factors for dverse cardiovascular events in DCM patients, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI) treatment (HR=0.45, 95%CI: 0.26-0.78, P=0.004) was independent protective factor. Kaplan-Meier survival analysis found no significant difference in the risk of MACEs between isolated DCM and DCM with LVNC (P=0.22). Similarly, there were no significant differences in the incidence of major heart failure, severe ventricular arrhythmia, and cardiovascular death between the two groups (all P>0.05). Conclusion: An increase in left ventricular end-diastolic diameter, moderate or severe mitral regurgitation, elevated N-terminal pro-B-type natriuretic peptide, and non use of ACEI/ARB/ARNI are independent predictors of cardiovascular events in DCM patients. There was no significant risk of MACEs in patients with isolated DCM and DCM with LVNC, and suggested that LVNC may be a unique phenotype and should be accurately managed in combination with genetic background.

Isolated left ventricular non-compaction cardiomyopathy: case report and brief review on diagnostic imaging methods

Left ventricular non-compaction cardiomyopathy (LVNC) is a rare congenital heart disease with an estimated incidence of 0.014-0.045% in a general population. It occurs due to a morphogenetic abnormality during embryogenesis that inhibits myocardial compaction and determines prominent trabeculae with deep intertrabecular spaces and thickening of the adjacent myocardium in two distinct layers. Diagnosis is generally established via transthoracic echocardiogram (TTE) with further confirmation with cardiac magnetic resonance (CMR). A 57-year-old male patient previously diagnosed with systemic arterial hypertension and chronic obstructive pulmonary disease reported chest pain and dyspnea upon exertion, headache, and dizziness. During outpatient investigation, the patient was submitted to a stress electrocardiogram that was positive for ischemia and led to a cineangiocoronariography with no signs of coronary artery obstruction. At the echocardiography lab, several trabeculations were detected in the apical region of the left ventricle. A diagnosis of LVNC was established and the results were confirmed via CMR. Management was initiated with the goal of symptom relief. LVNC is a relatively unknown pathology that is frequently underdiagnosed at earlier stages. As presented, we highlight the importance of multimodality imaging, especially TTE and CMR, in the diagnosis of this congenital heart condition.

Rare case of super-response to Cardiac Resynchronization Therapy in Macedonian patient with Dilated Left Ventricular Non-Compaction Cardiomyopathy

Background: Left ventricular non-compaction (LVNC) is rare cardiomyopathy with increased and prominent endomyocardial trabeculations also known as spongy myocardium. It is often found in association with a dilated cardiomyopathy (DCM) and has high incidence of Heart failure (HF). Cardiac resynchronization therapy (CRT) is currently recommended by the available guidelines for selected patients with Heart failure with reduced ejection fraction (HFrEF). Aim: Our case report aims to highlight the therapeutic benefits and superresponse to CRT in a patient with Left ventricular non-compaction cardiomyopathy and HFrEF. Case report: 55-year-old Macedonian male patient with HFrEF, Left bundle branch block (LBBB) remained symptomatic (NYHA III) despite optimal medical treatment (OMT). Echocardiography and CMR findings were in addition to dilated and left ventricular non-compaction cardiomyopathy. Cardiac resynchronization therapy was indicated and 18 months after implantation of CRT-P device we have achieved complete and utter reversibility of systolic myocardial function (EF from 23% to 53%), left ventricular internal diameter was reduced from 90mm to 64mm, left ventricular end systolic volume (LVESV) was reduced from 319ml to 98ml and patient quality of life significantly improved. Conclusion: Cardiac resynchronization therapy is a safe and valuable method of treatment for patients with HFrEF due to dilated left ventricular non-compaction cardiomyopathy.

Titin: The Missing Link in Cardiac Physiology

Titin, an extraordinary protein known for its colossal size and multifaceted roles, is a cornerstone in the structural and functional dynamics of striated muscle tissues, including the heart and skeletal muscles. Its sheer enormity, with a molecular weight exceeding 3000 kDa, is paralleled only by the immense influence it exerts on muscle physiology. This review will delve into the remarkable structural organization of Titin and the genetics of this molecule, including the common mutations resulting in various cardiomyopathies. We will delve deeper into its role in dilated cardiomyopathy, familial restrictive cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction cardiomyopathy. This review culminates by discussing the prospects of therapeutic strategies targeting Titin. While these interventions remain primarily theoretical, the possibilities are intriguing. Patients with Titin truncation mutations present unique challenges, but innovative approaches like gene therapy or preemptive treatments with drugs such as angiotensin-converting enzyme inhibitors or beta-blockers offer hope. This multi-pronged approach highlights the significance of understanding Titin’s multifaceted role and its potential as a target for future therapeutic interventions.

Severe Regurgitant Bicuspid Aortic Valve in a Patient with Overlapping Left Ventricular Noncompaction and Asymmetrical Septal Hypertrophy

Abstract Overlapping of left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy in the same patient is rare and is associated with a more severe clinical course and unfavorable prognosis. The present report describes the case of a severely regurgitant bicuspid aortic valve in a 68-year-old man with overlapping LVNC and asymmetrical septal hypertrophy. Aortic valve replacement controlled the left ventricular dilatation that occurred secondary to the volume overload induced by the valvular disease. However, even 3 years postoperatively, severe systolic dysfunction persisted due to the preexisting myocardial disease, requiring close and lifelong follow-up with special attention to life-threatening arrhythmias and thromboembolism.

Kiosk 2Q-TA-09 - Cardiac Magnetic Resonance (CMR) in the Diagnosis of Left Ventricular Noncompaction Cardiomyopathy: A Complex Clinical Presentation

Kiosk 2Q-TA-09 - Cardiac Magnetic Resonance (CMR) in the Diagnosis of Left Ventricular Noncompaction Cardiomyopathy: A Complex Clinical Presentation

Kiosk 3R-TC-09 - Differentiating Excessive Trabeculations FBom Left Ventricular Non-compaction Cardiomyopathy Utilizing Cardiovascular Magnetic Resonance

Kiosk 3R-TC-09 - Differentiating Excessive Trabeculations FBom Left Ventricular Non-compaction Cardiomyopathy Utilizing Cardiovascular Magnetic Resonance

Myocardial Mechanics and Associated Valvular and Vascular Abnormalities in Left Ventricular Noncompaction Cardiomyopathy.

Left ventricular (LV) non-compaction (LVNC) is a rare genetic cardiomyopathy due to abnormal intra-uterine arrest of compaction of the myocardial fibers during endomyocardial embryogenesis. Due to the partial or complete absence of LV compaction, the structure of the LV wall shows characteristic abnormalities, including a thin compacted epicardium and a thick non-compacted endocardium with prominent trabeculations and deep intertrabecular recesses. LVNC is frequently associated with chronic heart failure, life-threatening ventricular arrhythmias, and systemic embolic events. According to recent findings, in the presence of LVNC, dysfunctional LV proved to be associated with left atrial volumetric and functional abnormalities and consequential dilated and functionally impaired mitral annulus, partly explaining the higher prevalence of regurgitation. Although the non-compaction process morphologically affects only the LV, signs of remodeling of the right heart were also detected. Moreover, dilation and stiffening of the aorta were present. The aim of the present detailed review was to summarize findings regarding changes in cardiac mechanics, valvular abnormalities, and vascular remodeling detected in patients with LVNC.

Concealed Inherited Cardiomyopathies Detected in Cardio-Oncology Screening.

Basal cardiovascular risk assessment in cardio-oncology is essential. Integrating clinical information, ECG and transthoracic echocardiogram can identify concealed inherited cardiomyopathies (ICMPs) with potential added risk of cardiotoxicity. We aimed to evaluate the impact of our Cardio-Oncology Unit design in detecting concealed ICMPs. We carried out a retrospective study of all consecutive breast cancer patients referred to the Cardio-Oncology Unit for cardiac evaluation (2020-2022). ICMPs diagnosis was provided according to ESC guidelines and underwent genetic testing. ICMPs prevalence in this cohort was compared to the highest and lowest frequency reported in the general population. Among 591 breast cancer patients, we identified eight patients with ICMPs: one arrhythmogenic cardiomyopathy (ACM), three familial non-ischemic dilated cardiomyopathy (DCM), three hypertrophic cardiomyopathy (HCM) and one left ventricular non-compaction cardiomyopathy (LVNC), which has now been reclassified as non-dilated left ventricular cardiomyopathy. The number of ICMPs identified was within the expected range (neither overdiagnosed nor overlooked): ACM 0.0017 vs. 0.0002-0.001 (p 0.01-0.593); DCM 0.0051 vs. 0.002-0.0051 (p 0.094-0.676); HCM 0.005 vs. 0.0002-0.002 (p < 0.001-0.099); LVCN 0.0017 vs. 0.00014-0.013 (p 0.011-0.015). Genetic testing identified a pathogenic FLNC variant and two pathogenic TTN variants. Opportunistic screening of ICMPs during basal cardiovascular risk assessment can identify high-risk cancer patients who benefit from personalized medicine and enables extension of prevention strategies to all available relatives at concealed high cardiovascular risk.

Improving a Deep Learning Model to Accurately Diagnose LVNC.

Accurate diagnosis of Left Ventricular Noncompaction Cardiomyopathy (LVNC) is critical for proper patient treatment but remains challenging. This work improves LVNC detection by improving left ventricle segmentation in cardiac MR images. Trabeculated left ventricle indicates LVNC, but automatic segmentation is difficult. We present techniques to improve segmentation and evaluate their impact on LVNC diagnosis. Three main methods are introduced: (1) using full 800 × 800 MR images rather than 512 × 512; (2) a clustering algorithm to eliminate neural network hallucinations; (3) advanced network architectures including Attention U-Net, MSA-UNet, and U-Net++.Experiments utilize cardiac MR datasets from three different hospitals. U-Net++ achieves the best segmentation performance using 800 × 800 images, and it improves the mean segmentation Dice score by 0.02 over the baseline U-Net, the clustering algorithm improves the mean Dice score by 0.06 on the images it affected, and the U-Net++ provides an additional 0.02 mean Dice score over the baseline U-Net. For LVNC diagnosis, U-Net++ achieves 0.896 accuracy, 0.907 precision, and 0.912 F1-score outperforming the baseline U-Net. Proposed techniques enhance LVNC detection, but differences between hospitals reveal problems in improving generalization. This work provides validated methods for precise LVNC diagnosis.

Multidisciplinary approach in cardiomyopathies: From genetics to advanced imaging.

Cardiomyopathies are myocardial diseases characterized by mechanical and electrical dysfunction of the heart muscle which could lead to heart failure and life-threatening arrhythmias. Certainly, an accurate anamnesis, a meticulous physical examination, and an ECG are cornerstones in raising the diagnostic suspicion. However, cardiovascular imaging techniques are indispensable to diagnose a specific cardiomyopathy, to stratify the risk related to the disease and even to track the response to the therapy. Echocardiography is often the first exam that the patient undergoes, because of its non-invasiveness, wide availability, and cost-effectiveness. Cardiac magnetic resonance imaging allows to integrate and implement the information obtained with the echography. Furthermore, cardiomyopathies' genetic basis has been investigated over the years and the list of genetic mutations deemed potentially pathogenic is expected to grow further. The aim of this review is to show echocardiographic, cardiac magnetic resonance imaging, and genetic features of several cardiomyopathies: dilated cardiomyopathy (DMC), hypertrophic cardiomyopathy (HCM), arrhythmogenic cardiomyopathy (ACM), left ventricular noncompaction cardiomyopathy (LVNC), myocarditis, and takotsubo cardiomyopathy.

Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-β Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice.

PRDM16 plays a role in myocardial development through TGF-β (transforming growth factor-beta) signaling. Recent evidence suggests that loss of PRDM16 expression is associated with cardiomyopathy development in mice, although its role in human cardiomyopathy development is unclear. This study aims to determine the impact of PRDM16 loss-of-function variants on cardiomyopathy in humans. Individuals with PRDM16 variants were identified and consented. Induced pluripotent stem cell-derived cardiomyocytes were generated from a proband hosting a Q187X nonsense variant as an in vitro model and underwent proliferative and transcriptional analyses. CRISPR (clustered regularly interspaced short palindromic repeats)-mediated knock-in mouse model hosting the Prdm16Q187X allele was generated and subjected to ECG, histological, and transcriptional analysis. We report 2 probands with loss-of-function PRDM16 variants and pediatric left ventricular noncompaction cardiomyopathy. One proband hosts a PRDM16-Q187X variant with left ventricular noncompaction cardiomyopathy and demonstrated infant-onset heart failure, which was selected for further study. Induced pluripotent stem cell-derived cardiomyocytes prepared from the PRDM16-Q187X proband demonstrated a statistically significant impairment in myocyte proliferation and increased apoptosis associated with transcriptional dysregulation of genes implicated in cardiac maturation, including TGF-β-associated transcripts. Homozygous Prdm16Q187X/Q187X mice demonstrated an underdeveloped compact myocardium and were embryonically lethal. Heterozygous Prdm16Q187X/WT mice demonstrated significantly smaller ventricular dimensions, heightened fibrosis, and age-dependent loss of TGF-β expression. Mechanistic studies were undertaken in H9c2 cardiomyoblasts to show that PRDM16 binds TGFB3 promoter and represses its transcription. Novel loss-of-function PRDM16 variant impairs myocardial development resulting in noncompaction cardiomyopathy in humans and mice associated with altered TGF-β signaling.

The Trouble with Trabeculation: How Genetics Can Help to Unravel a Complex and Controversial Phenotype.

Excessive trabeculation of the cardiac left ventricular wall is a complex phenotypic substrate associated with various physiological and pathological processes. There has been considerable conjecture as to whether hypertrabeculation contributes to disease and whether left ventricular non-compaction (LVNC) cardiomyopathy is a distinct pathology. Building on recent insights into the genetic basis of LVNC cardiomyopathy, in particular three meta-analysis studies exploring genotype-phenotype associations using different methodologies, this review examines how genetic research can advance our understanding of trabeculation. Three groups of genes implicated in LVNC are described-those associated with other cardiomyopathies, other cardiac/syndromic conditions and putatively with isolated LVNC cardiomyopathy-demonstrating how these findings can inform the underlying pathologies in LVNC patients and aid differential diagnosis and management in clinical practice despite the limited utility suggested for LVNC genetic testing in recent guidelines. The outstanding questions and future research priorities for exploring the genetics of hypertrabeculation are discussed.

Thinning of compact layer and systolic dysfunction in isolated left ventricular non-compaction: A cardiac magnetic resonance study

BackgroundThe Petersen’ index reflects an excess of myocardial trabeculation which is not a specific morpho-functional feature of left ventricular non-compaction (LVNC) cardiomyopathy, but a “phenotypic trait” even observed in association with other myocardial diseases and over-loading conditions. The present study was designed to evaluate the relation between a critical thinning of compact layer and the development of systolic dysfunction and LVNC cardiomyopathy. MethodsWe compared CMR morpho-functional features and measurements of LV wall thickness using a 17 segment model of a cohort of patients fulfilling the Petersen criterion for LVNC with LV systolic dysfunction versus those of a cohort of age- and sex-matched controls with LVNC and preserved LV systolic function. All the study patients had an “isolated” LVNC defined as positive Petersen criterion in the absence of other diseases such as hypertrophic and dilated cardiomyopathy, valvular heart disease, or congenital heart disease and over-loading conditions. Resultshe study population included 33 patients with “isolated” LVNC: 11 consecutive index patients with a reduced LV ejection fraction (LVNCrEF) and 22 controls with a preserved LVEF (LVNCpEF). The compact myocardial layer was thinner in patients with LVNCrEF than in those with LVNCpEF patients, both in mid-ventricular and apical LV segments. On linear regression analysis, there was a linear correlation between median thickness of mid-ventricular free wall segments and left ventricular ejection fraction (r = 0.51, p = 0.005). On the ROC curves analysis, ≥2 segments with a compact myocardial layer <5 mm in the free wall mid-ventricular segments showed the best accuracy for reduced LVEF (100% sensitivity and 60% specificity; AUC 0.81, p < 0.01). The negative predictive value for LV systolic dysfunction of <2 free wall mid ventricular segments <5 mm was 100%. On quantitative analysis, the mass of papillary muscles was lower in patients with LVNCrEF [1.2 (0.8–1.4) versus 1.6 (1.1–1.8) g/mq; p = 0.08]. Conclusions: A thinned compact layer of mid-ventricular segments of the LV free wall was associated with a reduced systolic function and “isolated” LVNC cardiomyopathy.

Role and prognostic relevance of cardiac magnetic resonance imaging in the assessment of left ventricular non-compaction cardiomyopathy: review and meta-analysis

Abstract Background Left ventricular non-compaction (LVNC) is a heterogeneous myocardial disorder characterized by prominent myocardial trabeculation with deep inter-trabecular recesses, thin epicardial layer of compacted myocardium and extensive non-compacted inner muscular layer. Although several diagnostic criteria have been proposed, prediction of major adverse cardiovascular and cerebrovascular events (MACCE) still remains challenging in patients with LVNC. Objectives Objectives of our study were to perform systemic review and meta-analysis of published literature evaluating role and prognostic significance of the late gadolinium enhancement (LGE) in cardiac magnetic resonance imaging (CMR) study, its association with MACCE and characteristics of CMR derived feature-tracking (FT) strain analysis in patients with LVNC. Methods The objectives, literature search strategies, inclusion and exclusion criteria, outcome measurements, and methods of statistical analysis were analyzed according to an established protocol of the cochrane collaboration steps and meta-analysis of observational studies in epidemiology recommendations (MOOSE). Case control studies with evaluated prevalence of LGE in LVNC cardiomyopathy patients with and without MACCE and studies comparing FT strain: left ventricular global longitudinal (LV GLS), global circumferential (GCS) and global radial (GRS) strain between patients with and without LVNC has been included in the analysis. Results A total of 936 papers were collected according to our searching criteria, of those 9 studies including 416 LVNC cardiomyopathy patients with MACCE and 673 LVNC patients without MACCE and with evaluated LGE (including three studies with LVNC and heart failure), also 6 studies including 267 LVNC patients and 283 controls with evaluated FT LV GLS, GCS and GRS (measured in four studies) were selected. LGE was more frequently observed in LVNC patients with MACCE as compared to those without MACCE [RR (95 %CI) 2.52 (1.63 to 3.88); p&amp;lt;0.00001] (Fig.1). FT LV GLS was significantly more affected in LVNC patients compared to controls (St. mean difference (95 %CI): 1.40 (0.69 to 2.11); p&amp;lt;0.00001], as well as GCS and GRS (Fig. 2). Conclusions In patients with LVNC evaluated with CMR, LGE shows association with adverse cardiovascular and cerebrovascular events. CMR deformation indices: FT LV GLS, GCS, and GRS are significantly affected in patients with LVNC as compared to controls. This new CMR technique may be a complementary tool for timely detection and differentiation of LVNC cardiomyopathy and to avoid life threatening adverse events.Figure 1Figure 2

The role of TBX20 truncating variants in dilated and left ventricular non-compaction cardiomyopathy

Abstract Background The genetic cause of dilated cardiomyopathy (DCM) remains unexplained in a considerable proportion of cases. TBX20, the T-Box transcription factor 20 gene, has been linked to cardiac septal defects. Although only a few case reports have described an association between TBX20 and DCM/left ventricular non-compaction (LVNC), there are no case-control studies available, and TBX20 is still considered a gene with limited evidence for these phenotypes. Objectives This study sought to investigate the relationship between truncating variants in TBX20 (TBX20tv) and the development of DCM and LVNC. Methods TBX20 was sequenced using massive parallel sequencing in 7,463 unrelated probands with DCM/LVNC and 22,773 probands with other diagnoses (e.g., hypertrophic or arrhythmogenic cardiomyopathy, channelopathies, or aortic diseases) as internal controls. It was tested for enrichment and cosegregation of TBX20tv in DCM/LVNC, and clinical characteristics and outcomes in carriers were analyzed. Results Twenty-four probands with 22 TBX20tv were identified. Variant frequencies were significantly higher in patients with DCM/LVNC (24/7,463; 0.29%) than in internal controls (2/22,773; 0.008%) or controls from the gnomAD database (4/124,098; 0.003%), with an OR of 70.18 (CI95%: 9.48 to 519.8; p &amp;lt;0.0001) and 95.61 (CI95%: 33.06-276.55; p &amp;lt;0.0001), respectively. Cosegregation was studied in 21 families, identifying 57 carriers, of whom 43 (75.4%) had cardiac involvement. A combined LODs score of 4.41 was obtained, which is indicative of very strong segregation. Regarding clinical characteristics, the mean age at diagnosis was 37 years old, and 50% of carriers were female. Forty-six percent developed left-ventricular dysfunction, which was moderate to severe in half of the cases. Three carriers received a heart transplant, and another carrier died due to heart failure. Congenital heart defects were present in 16 patients (28.1%). Valvular involvement was the most frequent congenital abnormality (5 cases had bicuspid aortic valve, and another 5 had mitral valve defects), followed by heart septal defects (3 atrial and 3 ventricular); coronary anomalies (2) and aortic coarctation (2) were also detected. In some patients, these defects presented as complex congenital heart disease. Conclusions TBX20tv are associated with the development of dilated and non-compaction cardiomyopathy, and the presence of congenital heart defects is also common. Although some carriers, particularly younger ones, may not present the phenotype, nearly half of them experience ventricular dysfunction, and significant cardiac events, such as cardiac death or transplantation, are not uncommon. Therefore, the TBX20 gene should be routinely included in genetic testing panels for DCM and LVNC.

Abstract 13343: Left Ventricular Noncompaction Cardiomyopathy in a Family With Dolichol Kinase Congenital Disorder of Glycosylation

Introduction: During embryogenesis, failure of spongy, sinusoidal myocardium to condense results in left ventricular noncompaction cardiomyopathy (LVNC). The resulting LV is hypertrophic but loosely organized. LVNC is associated with heart failure (HF), arrhythmias, and thromboembolic events. Case: A 41 year old man with a history of non-ischemic HF with recovered ejection fraction associated with signs of LVNC, LV thrombus, and ischemic stroke while compliant with rivaroxaban has been known to cardiology services for years. His brother who also exhibited LVNC and suffered thrombotic events died at age 31 from advanced HF. Uniquely, EKG for both brothers showed exceptionally low ventricular voltage, with P waves of higher amplitude than R waves. Genetic testing revealed a homozygous variant of unknown significance (VUS) in dolichol kinase (c.863_865del)(p.Leu288del) establishing a diagnosis of congenital disorder of glycosylation (DOLK-CDG). Metabolic testing was abnormal and, given phenotypic overlap of the brothers, it is likely that the VUS caused this clinical presentation. Discussion: LVNC has never previously been linked with DOLK-CDG. In the literature, 27 patients with DOLK-CDG have been described ranging from 3 days to 16.5 years old at time of death. Nearly all patients expressed dilated cardiomyopathy, while others expressed a combination of ichthyosis, dysmorphism, and neurological dysfunction. Our patient reported good health until presentation with chest pain at age 35 when he was discovered to have ejection fraction of 40% and LV thrombus. The most curious finding was the paradoxically low ventricular EKG voltage in both brothers, dissimilar to the hypertrophic pattern commonly seen in LVNC. Yet all common MR criteria were met, strongly suggesting LVNC. Given the similarities in the presentation between brothers, this patient was preemptively referred for transplant.

Left ventricular non-compaction cardiomyopathy in adult congenital heart disease tetralogy of Fallot

Left ventricular non-compaction cardiomyopathy in adult congenital heart disease tetralogy of Fallot

Renal dysfunction and outcome in left ventricular non-compaction.

While renal function has been observed to inversely correlate with clinical outcome in other cardiomyopathies, its prognostic significance in patients with left ventricular non-compaction cardiomyopathy (LVNC) has not been investigated. The aim of this study was to determine the prognostic value of renal function in LVNC patients. Patients with isolated LVNC as diagnosed by echocardiography and/or magnetic resonance imaging in 4 Swiss centers were retrospectively analyzed for this study. Values for creatinine, urea, and estimated glomerular filtration rate (eGFR) as assessed by the CKD-EPI 2009 formula were collected and analyzed by a Cox regression model for the occurrence of a composite endpoint (death or heart transplantation). During the median observation period of 7.4 years 23 patients reached the endpoint. The ageand gender-corrected hazard ratios (HR) for death or heart transplantation were: 1.9 (95% confidence interval [CI] 1.4-2.6) for each increase over baseline creatinine level of 30 μmol/L (p < 0.001), 1.6 (95% CI 1.2-2.2) for each increase over baseline urea level of 5 mmol/L (p = 0.004), and 3.6 (95% CI 1.9-6.9) for each decrease below baseline eGFR level of 30 mL/min (p ≤ 0.001). The HR (log2) for every doubling of creatinine was 7.7 (95% CI 3-19.8; p < 0.001), for every doubling of urea 2.5 (95% CI 1.5-4.3; p < 0.001), and for every bisection of eGFR 5.3 (95% CI 2.4-11.6; p < 0.001). This study provides evidence that in patients with LVNC impairment in renal function is associated with an increased risk of death and heart transplantation suggesting that kidney function assessment should be standard in risk assessment of LVNC patients.