A case report of autosomal recessive polycystic kidney disease with noncompaction of ventricular myocardium: coincidence or different manifestations of ciliopathy?

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited cystic disease characterized by bilateral renal cyst formation and congenital liver fibrosis. Cardiovascular disorders such as noncompaction of ventricular myocardium (NVM) have not been reported with ARPKD. CASE PRESENTATION: A 5-month-old girl was examined after presenting with a fever and turbid urine for one day and was diagnosed as urinary tract infection. Urinary ultrasound showed multiple round, small cysts varying in size in both kidneys. Genetic testing revealed two heterozygous mutations and one exon deletion in the polycystic kidney and hepatic disease 1 gene, indicating a diagnosis of ARPKD. During hospitalization, she was found to have chronic heart failure after respiratory tract infection, with an ejection fraction of 29% and fraction shortening of 13%. When the patient was 15 months old, it was found that she had prominent trabeculations and deep intertrabecular recesses with the appearance of blood flow from the ventricular cavity into the intertrabecular recesses by echocardiography. The noncompaction myocardium was 0.716 cm and compaction myocardium was 0.221 cm (N/C = 3.27), indicating a diagnosis of NVM. Liver and kidney function remained normal during four-year follow-up. CONCLUSIONS: This is the first report of NVM in a patient with ARPKD. It is unsure if the coexistence of NVM and ARPKD is a coincidence or they are different manifestations of ciliary dysfunction in the heart and kidneys.

Coronary Angiography in Patients With Left Ventricular Hypertrabeculation/Noncompaction.

BACKGROUND: Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown pathogenesis, frequently associated with neuromuscular disorders. The relevance of coronary artery disease (CAD) in LVHT is largely unknown. This study aimed to assess the role of CAD as a prognostic marker in LVHT. METHODS: Data from patients with LVHT were collected from an echocardiographic laboratory. The hospital information system was retrospectively screened for coronary angiography. The association of CAD with clinical, echocardiographic, and neurologic baseline parameters was assessed. End points were all-cause death and heart transplantation. RESULTS: A total of 154 patients (mean [SD] age, 57 [13.7] years; 31% female) who had undergone coronary angiography between 1995 and 2020 were included in the study. Coronary angiography disclosed CAD in 53 of 154 patients. Patients with CAD were older (mean [SD] age of, 64.2 [12.9] years vs 52.7 [12.4] years; P < .001); more frequently had angina pectoris (P = .05), diabetes (P = .002), and hypertension (P = .03); and more frequently had 3 or more electrocardiographic abnormalities (P = .04) than patients without CAD. During a median (IQR) follow-up period of 6.48 (2.44-11.20) years, 39% of patients reached an end point (death, n = 56; heart transplantation, n = 4). Mortality was 4.5% per year, and the rate of death or heart transplantation did not differ between patients with and without CAD (P = .26). Patients with 3-vessel disease had a worse prognosis than patients with 1- or 2-vessel disease (P = .046). CONCLUSION: In patients with LVHT, CAD does not appear to be associated with an increased rate of death or heart transplantation.

Noncompaction Cardiomyopathy: Issues, Contradictions, and Search for Effective Diagnostic Criteria. Literature Review. Part 1.

Active research of noncompaction cardiomyopathy (NCM) has been going on for more than 30 years. A significant amount of information has been accumulated that is familiar to a much larger number of specialists than in the most recent past. Despite this, numerous issues remain unresolved, ranging from classification (congenital or acquired, nosology or morphological phenotype) to the ongoing search for clear diagnostic criteria that separate NCM from physiological hypertrabecularity and secondary noncompaction myocardium with the background of existing chronic processes. Meanwhile, a high risk of adverse cardiovascular events in a certain group of people with NCM is quite high. These patients need timely and often quite aggressive therapy. This review of sources of scientific and practical information is devoted to the current aspects of the classification, extremely diverse clinical picture, extremely complex genetic and instrumental diagnosis of NCM, and the possibilities of its treatment. The purpose of this review is to analyze current ideas about the controversial problems of noncompaction cardiomyopathy. The material for its preparation is the numerous sources of databases Web Science, PubMed, Google Scholar, eLIBRARY. As a result of their analysis, the authors tried to identify and summarize the main problems of the NCM and identify the ways to resolve them.

Noncompaction Cardiomyopathy: Issues, Contradictions and Search for Effective Diagnostic Criteria. Literature Review. Part 2.

Active research of noncompaction cardiomyopathy (NCM) has been going on for more than 30 years. A significant amount of information has been accumulated that is familiar to a much larger number of specialists than in the most recent past. Despite this, numerous issues remain unresolved, ranging from classification (congenital or acquired, nosology, or morphological phenotype) to the ongoing search for clear diagnostic criteria that separate NCM from physiological hypertrabecularity and secondary noncompaction myocardium with the background of existing chronic processes. Meanwhile, a high risk of adverse cardiovascular events in a certain group of people with NCM is quite high. These patients need timely and often quite aggressive therapy. This review of sources of scientific and practical information is devoted to the current aspects of the classification, extremely diverse clinical picture, extremely complex genetic, and instrumental diagnosis of NCM, and the possibilities of its treatment. The purpose of this review is to analyze current ideas about the controversial problems of noncompaction cardiomyopathy. The material for its preparation is the numerous sources of databases Web Science, PubMed, Google Scholar, eLIBRARY. As a result of their analysis, the authors tried to identify and summarize the main problems of the NCM and identify the ways to resolve them.

Biventricular Noncompaction Cardiomyopathy in a Patient Presenting With a New Cerebrovascular Event.

Noncompaction (NC) cardiomyopathy (NCCM) is a rare, genetically heterogeneous cardiomyopathy (CM) caused by failure to compact the intertrabecular recesses of the myocardium. This condition usually affects the apical segment of the left ventricle, yet there are noted basal segment, biventricular, and right ventricular predominant cases. NCCM is largely diagnosed in the pediatric population; however, there is increasing recognition in older patients with heart failure and stroke and patients with arrhythmias. Treatment focuses on symptomatic management of heart failure, anticoagulation, and implantable cardiac defibrillators.

Left Ventricular Noncompaction Cardiomyopathy: Left Ventricular Dilation and Dysfunction at Baseline Portend the Risk of Death or Heart Transplantation.

BACKGROUND: Left ventricular noncompaction (LVNC) is associated with genetic and phenotypic variability that influences outcomes. We aimed to identify risk factors for death or heart transplantation (HTx) in a paediatric LVNC cohort. METHODS: We reviewed patients < 18 years of age (2001-2018) with LVNC, either isolated (I-LVNC) or with dilated phenotype (D-LVNC), and at least mildly reduced left ventricular ejection fraction (EF). Patients with dilated cardiomyopathy (DCM) were included as control subjects. Descriptive statistics, multivariate analysis, and time-to-event analysis were used. RESULTS: We included 188 patients, 34 (18%) with I-LVNC, 37 (20%) with D-LVNC, and 117 (62%) with DCM. Overall median age at diagnosis was 1.08 years (interquartile range [IQR] 0.22-10.65) and median follow-up was 1.4 years (IQR 0.2-5.2) years. I-LVNC patients' median baseline LVEF was 47%, compared with 33% for D-LVNC, and 21% for DCM (P < 0.0001); 62% of I-LVNC patients developed moderate to severe LV dysfunction during follow-up. The incidence of death or transplantation was 43.6% in the overall cohort. Freedom from death or HTx at 10 years after diagnosis was 88.6% (95% CI 76%-100%) for I-LVNC, 47% (95% CI 29%-65%) for D-LVNC, and 42.3% (95% CI 33%-52%) for DCM. On multivariable analysis, baseline LVEF and LV end-diastolic diameter (LVEDD) z-score were associated with death or transplantation. Patients with a baseline LVEDD z-score > 4 and moderate to severe LV dysfunction had a transplantation-free survival of 38%. CONCLUSIONS: Baseline LV dilation and systolic dysfunction were independently associated with progression to death or HTx in LVNC patients.

The interaction protein of SORBS2 in myocardial tissue to find out the pathogenic mechanism of LVNC disease.

BACKGROUND: Left ventricular noncompaction cardiomyopathy (LVNC) is a cardiac disorder characterized by an excessive trabecular meshwork of deep intertrabecular recesses within the ventricular myocardium. Sorbin and SH3 domain-containing protein 2 (SORBS2) converges on the actin and microtubule cytoskeleton. Here, we investigated the proteins interacting with SORBS2 to elucidate the pathogenic mechanism of LVNC. As reported in previous studies, SORBS2 enhances the occurrence of LVNC by potentiating heart failure, but the specific mechanism remains unclear. METHODS: Building from our previous finding of elevated SORBS2 levels in LVNC hearts, we screened for proteins interacting with SORBS2 by proteomics and conducting IP experiments. Co-IP and immunofluorescence were used to verify the effects. RESULTS: We selected several proteins with high scores and high coverage that could be closely related to SORBS2 according to earlier reports showing a correlation with LVNC for verification. We finally obtained several proteins that were related to the pathogenesis of LVNC and also interacted with SORBS2, such as α-actinin, ß-tubulin, MYH7, FLNA, MYBPC3, YWHAQ and DES, and YWHAQ was the most associated. CONCLUSIONS: We focused on the YWHAQ protein, and we identified a novel mechanism through which SORBS2 interacts with YWHAQ, having a negative effect on the cell cycle, potentially leading to LVNC.

Clinical Risk Prediction in Patients With Left Ventricular Myocardial Noncompaction.

BACKGROUND: Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis. OBJECTIVES: This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) and to identify LVNC cases without events during long-term follow-up. METHODS: This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality. RESULTS: A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up. CONCLUSIONS: LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management.

Left Ventricular Noncompaction Cardiomyopathy as a Potential Cause of Bilateral Posterior Cerebral Artery Stroke - a Rare and Unique Clinical Occurrence.

BACKGROUND Bilateral posterior cerebral artery (PCA) occlusions are exceedingly rare, and are considered a devastating phenomenon that presents as cortical blindness. Predominant causes of PCA infarcts include cardiac and arterial embolisms. Left ventricular noncompaction (LVNC) cardiomyopathy is also an extremely rare cardiopathology. Several reports describe stroke as a potential manifestation of LVNC, but bilateral PCA infarcts are likely also caused by underlying LVNC cardiomyopathy, although this has not yet been reported. CASE REPORT A 63-year-old man presented to the emergency department of an outside hospital with acute vision loss in both eyes and dysarthria. His neurological examination necessitated an emergent stroke evaluation. His electrocardiogram and telemetry at admission did not reveal arrhythmia. He underwent an emergency endovascular thrombectomy at our facility. During the post-intervention stroke workup, a transthoracic echocardiogram with contrast showed left ventricle dilation, with an ejection fraction (EF) of 29%. Subsequent cardiac magnetic resonance imaging confirmed the presence of LVNC cardiomyopathy. He was started on therapeutic anticoagulation (apixaban) and remained stable neurologically during the 3-month followup, with some residual visual field deficits. His cardiac outcome also improved (stress test was unremarkable for any cardiac ischemia, and an echocardiogram showing improved EF of 40%). CONCLUSIONS Our report is distinct, as it presents 2 exceedingly rare events in a patient: the occurrence of simultaneous bilateral PCA infarcts and LVNC cardiomyopathy. Prompt and accurate diagnosis was pivotal to the successful management of both conditions. Prospective studies are warranted to further knowledge of LVNC pathophysiology and the occurrence of stroke in such patients so that comprehensive management plans can be devised.

Clinical outcomes in patients with left ventricle trabeculation or noncompaction.

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

Prognostic value of plasma big endothelin-1 in left ventricular non-compaction cardiomyopathy.

OBJECTIVE: To determine the prognostic role of big endothelin-1 (ET-1) in left ventricular non-compaction cardiomyopathy (LVNC). METHODS: We prospectively enrolled patients whose LVNC was diagnosed by cardiac MRI and who had big ET-1 data available. Primary end point was a composite of all-cause mortality, heart transplantation, sustained ventricular tachycardia/fibrillation and implanted cardioverter defibrillator discharge. Secondary end point was cardiac death or heart transplantation. RESULTS: Altogether, 203 patients (median age 44 years; 70.9% male) were divided into high-level (≥0.42 pmol/L) and low-level (<0.42 pmol/L) big ET-1 groups according to the median value of plasma big ET-1 levels. Ln big ET-1 was positively associated with Ln N-terminal pro-brain natriuretic peptide, left ventricular diameter, but negatively related to age and Ln left ventricular ejection fraction. Median follow-up was 1.9 years (IQR 0.9-3.1 years). Kaplan-Meier analysis showed that, compared with patients with low levels of big ET-1, those with high levels were at greater risk for meeting both primary (p<0.001) and secondary (p<0.001) end points. The C-statistic estimation of Ln big ET-1 for predicting the primary outcome was 0.755 (95% CI 0.685 to 0.824, p<0.001). After adjusting for confounding factors, Ln big ET-1 was identified as an independent predictor of the composite primary outcome (HR 1.83, 95% CI 1.27 to 2.62, p=0.001) and secondary outcome (HR 1.93, 95% CI 1.32 to 2.83, p=0.001). CONCLUSIONS: Plasma big ET-1 may be a valuable index to predict the clinical adverse outcomes in patients with LVNC.

Ventricular tachycardia triggered by pregnancy in left-ventricular non-compaction cardiomyopathy: a controversial indication to automated defibrillator implantation.

Left-ventricular non-compaction (LVNC) is a rare form of cardiomyopathy. Its clinical presentation is highly variable and during pregnancy is frequently associated with heart failure, embolic events, and arrhythmias. Herein we report a case of a woman with left ventricular non-compaction who had an automated defibrillator implantation for recurrent ventricular arrhythmias during pregnancy. During pregnancy and at long-term follow-up no interventions of the device were documented. In conclusion, the management of malignant arrhythmias during pregnancy is one of the concerns for patients with LVNC and requires a careful approach in third-level centers.

Cardiac Emerinopathy: A Nonsyndromic Nuclear Envelopathy With Increased Risk of Thromboembolic Stroke Due to Progressive Atrial Standstill and Left Ventricular Noncompaction.

BACKGROUND: Mutations in the nuclear envelope genes encoding LMNA and EMD are responsible for Emery-Dreifuss muscular dystrophy. However, LMNA mutations often manifest dilated cardiomyopathy with conduction disturbance without obvious skeletal myopathic complications. On the contrary, the phenotypic spectrums of EMD mutations are less clear. Our aims were to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with EMD mutations. METHODS: Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51). RESULTS: We identified 3 X-linked recessive EMD mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction (LVNC), but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of LVNC with EMD has never been reported, we further genetically screened 102 LVNC patients and found a frameshift EMD mutation in a boy with progressive atrial standstill and LVNC without complications of muscular dystrophy. All 6 male EMD mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas 2 female carriers were asymptomatic. Notably, a strong family history of stroke observed in these families was probably due to the increased risk of thromboembolism attributable to both atrial standstill and LVNC. CONCLUSIONS: Cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with LVNC and increased risk of thromboembolism.

Congenital left ventricular aneurysm with myocardial noncompaction pattern.

Congenital left ventricular aneurysm or diverticulum is very rare. Most congenital left ventricular aneurysms are asymptomatic but some cause systemic embolization, left ventricular free wall rupture, or ventricular arrhythmias causing sudden cardiac death. A 29-year-old woman with congenital left ventricular aneurysm and nonsustained ventricular tachycardia underwent surgical plication of the aneurysm with left ventricular reshaping to improve heart failure symptoms, prevent rupture of the aneurysm wall and the possibility of thrombus formation, and excise the fibrotic tissue of the left ventricular aneurysm, which could be a trigger for left ventricular aneurysm arrhythmias. The postoperative course was unremarkable.

Non-compaction of ventricular myocardium with polycystic kidney disease with cardiogenic cerebral embolism.

Non-compaction of ventricular myocardium is a rare cardiomyopathy involving an early arrest of normal compaction of myocardium during fetal ontogenesis. Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary nephropathy characterised by multiple renal cysts replacing the renal parenchyma and extrarenal manifestations. Here, we report a case of 65-year-old man, chronic smoker, presented with sudden onset right brachial monoparesis, exertional dyspnoea, orthopnoea, bipedal swelling and diagnosed as a case of ADPKD with left ventricular non-compaction cardiomyopathy with acute left ventricular failure and cardiogenic cerebral embolism (no evidence of atrial fibrillation); based on characteristic appearance on two-dimensional echocardiography and cardiac magnetic resonance. The patient was managed with guideline-directed pharmacotherapy for heart failure and anticoagulation as a secondary stroke prevention measure. Through this case report, we try to discuss the association between two rare entities and individualisation of treatment options available as a case-based approach, as no standard treatment guidelines are available.

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

BACKGROUND: 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. METHODS: We systematically searched observational studies reporting the adverse outcomes related to LVNC. The primary end point was cardiovascular mortality. RESULTS: 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. CONCLUSIONS: 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.