Liver Involvement in Patients with Rare MBOAT7 Variants and Intellectual Disability: A Case Report and Literature Review.

The membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) protein is an acyltransferase catalyzing arachidonic acid incorporation into lysophosphatidylinositol. Patients with rare, biallelic loss-of-function variants of the MBOAT7 gene display intellectual disability with neurodevelopmental defects. The rs641738 inherited variant associated with reduced hepatic MBOAT7 expression has been linked to steatotic liver disease susceptibility. However, the impact of biallelic loss-of-function MBOAT7 variants on liver disease is not known. We report on a 2-year-old girl with MBOAT7-related intellectual disability and steatotic liver disease, confirming that MBOAT7 loss-of-function predisposes to liver disease.

Non-invasive evaluation of pulmonary capillary wedge pressure using the left atrial expansion index in mitral valve stenosis, prosthesis and repair.

Pulmonary capillary wedge pressure (PCWP) non-invasive evaluation is limited in patients with mitral valve (MV) stenosis, prosthesis, and surgical repair. This study aimed to assess the left atrial expansion index (LAEI) measured through transthoracic echocardiography (TTE) as a novel parameter for estimating PCWP in these challenging cardiac conditions. We performed a retrospective, cross-sectional study, including chronic cardiac patients receiving within 24 h a clinically indicated right heart catheterization (RHC) and transthoracic echocardiographic (TTE) exam. PCWP measured during RHC was used as the reference. TTE measurements were performed offline, blinded to RHC results. LAEI was calculated as LAEI = [(LAmaxVolume-LAminVolume)/LAminVolume] × 100. We included 167 patients (age = 73 ± 11.5 years; PCWP = 18 ± 7.7 mmHg) with rheumatic mitral valve (MV) stenosis (16.2%), degenerative MV stenosis (51.2%), MV prosthesis (18.0%), and MV surgical repair (13.8%). LAEI correlated logarithmically with PCWP, and the log-transformed LAEI (lnLAEI) showed a good linear association with PCWP (r = - 0.616; p < 0.001). lnLAEI was an independent PCWP determinant, providing added predictive value over conventional clinical (age, atrial fibrillation, heart rate, MV subgroups) and echocardiographic variables (LVEF, MV effective orifice area, MV mean gradient, net atrioventricular compliance, and pulmonary arterial systolic pressure). lnLAEI identified PCWP > 12 mmHg with AUC = 0.870, p < 0.001; and PCWP > 15 mmHg with AUC = 0.797, p < 0.001, with an optimal cut-off of lnLAEI < 3.69. The derived equation PCWP = 36.8-5.5xlnLAEI estimated the invasively measured PCWP ± 6.1 mmHg. In this cohort of patients with MV stenosis, prosthesis, and surgical repair, lnLAEI resulted in a helpful echocardiographic parameter for PCWP estimation.

Prognostic Significance of Feature-Tracking Right Ventricular Global Longitudinal Strain in Non-ischemic Dilated Cardiomyopathy.

Aims: Left ventricular global longitudinal strain (GLS) by cardiac magnetic resonance feature tracking (CMR-FT) analysis has shown an incremental prognostic value compared to classical parameters in non-ischemic dilated cardiomyopathy (NICM). However, less is known about the role of right ventricular (RV) GLS. Our objective was to evaluate the prognostic impact of RV-GLS by CMR-FT analysis in a population of NICM patients. Methods: In this multicenter study, we examined NICM patients evaluated with a comprehensive CMR-FT study. Major cardiac events (MACEs) were considered as the study primary outcome measure and were defined as a composite of (a) cardiovascular death, (b) cardiac transplant or destination therapy ventricular assist device, (c) hospitalization for life-threatening ventricular arrhythmias or implantable cardiac defibrillator appropriate intervention. Heart failure (HF) related events, including hospitalizations and life-threatening arrhythmia-related events were considered as secondary end-points. Receiver operating time-dependent analysis were used to calculate the possible additional effect of RV-GLS to standard evaluation. Results: We consecutively enrolled 273 patients. During a median follow-up of 39 months, 41 patients (15%) experienced MACEs. RV-GLS and LV late gadolinium emerged as the strongest prognostic CMR-FT variables: their association provided an estimated 3-year MACEs rate of 29%. The addition of RV-GLS significantly improved the prognostic accuracy in predicting MACEs with respect to the standard evaluation including LGE (areas under the curve from 0.71 [0.66-0.82] to 0.76 [0.66-0.86], p = 0.03). On competing risk analysis, RV-GLS showed a significant ability to reclassify overall both HF-related and life-threatening arrhythmia-related events, regardless of LV and RV ejection fraction. Conclusions: In NICM patients, RV-GLS showed a significant prognostic role in reclassifying the risk of MACEs, incremental with respect to standard evaluation with standard prognostic parameters.

New Candidates for Autism/Intellectual Disability Identified by Whole-Exome Sequencing.

Intellectual disability (ID) is characterized by impairments in the cognitive processes and in the tasks of daily life. It encompasses a clinically and genetically heterogeneous group of neurodevelopmental disorders often associated with autism spectrum disorder (ASD). Social and communication abilities are strongly compromised in ASD. The prevalence of ID/ASD is 1-3%, and approximately 30% of the patients remain without a molecular diagnosis. Considering the extreme genetic locus heterogeneity, next-generation sequencing approaches have provided powerful tools for candidate gene identification. Molecular diagnosis is crucial to improve outcome, prevent complications, and hopefully start a therapeutic approach. Here, we performed parent-offspring trio whole-exome sequencing (WES) in a cohort of 60 mostly syndromic ID/ASD patients and we detected 8 pathogenic variants in genes already known to be associated with ID/ASD (SYNGAP1, SMAD6, PACS1, SHANK3, KMT2A, KCNQ2, ACTB, and POGZ). We found four de novo disruptive variants of four novel candidate ASD/ID genes: MBP, PCDHA1, PCDH15, PDPR. We additionally selected via bioinformatic tools many variants in unknown genes that alone or in combination can contribute to the phenotype. In conclusion, our data confirm the efficacy of WES in detecting pathogenic variants of known and novel ID/ASD genes.

Left Atrial Expansion Index for Noninvasive Estimation of Pulmonary Capillary Wedge Pressure: A Cardiac Catheterization Validation Study.

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) plays a pivotal role in cardiac disease diagnosis and management. Right heart catheterization (RHC) invasively provides accurate PCWP measurement, but it is impractical for widespread use in all patients. The left atrial expansion index (LAEI), measured on transthoracic echocardiography, describes the relative left atrial volume increase during the left atrial reservoir phase. The aim of this study was to validate LAEI as a noninvasive parameter for PCWP estimation. METHODS: A total of 649 chronic cardiac patients (mean age, 66 ± 14 years; mean PCWP, 14 ± 7.6 mm Hg; mean left ventricular ejection fraction, 50 ± 15%) who underwent both clinically indicated RHC and transthoracic echocardiography within 24 hours were retrospectively enrolled. Patients were randomly divided into derivation (n = 509) and validation (n = 140) cohorts. PCWP was measured during RHC and defined as elevated when >12 mm Hg. Transthoracic echocardiographic parameters and LAEI were measured offline, blinded to RHC results. RESULTS: In the derivation cohort, LAEI correlated logarithmically with PCWP, and the log-transformed LAEI (lnLAEI) correlated linearly with PCWP (r = -0.73, P < .001). lnLAEI showed an independent and additive predictive role for PCWP estimation over clinical and diastolic dysfunction (DD) parameters. The diagnostic accuracy of lnLAEI for elevated PCWP identification (area under the curve = 0.875, P < .001; optimal lnLAEI cutoff < 4.02) was higher than either the single DD parameters or their combination. In the validation cohort, lnLAEI cutoff < 4.02 showed higher accuracy than the 2016 DD algorithm (88% vs 74%) for elevated PCWP identification. Finally, the equation PCWP = 38.3 - 6.2 × lnLAEI, obtained from the derivation cohort, predicted invasively measured PCWP in the validation cohort. CONCLUSIONS: In a cohort of patients with various chronic cardiac diseases, lnLAEI performed better than DD parameters and the 2016 DD algorithm for PCWP estimation. lnLAEI might be a useful echocardiographic parameter for noninvasive PCWP estimation.

Development and Validation of a Distal Embolization Risk Score During Primary Angioplasty in ST-Elevation Myocardial Infarction.

This study aims to develop and validate a new angiographic risk score to predict the risk of distal embolization (DE) during primary percutaneous coronary intervention (p-PCI) for ST-elevation myocardial infarction. Study included data from 1,200 patients who underwent p-PCI. The cohort was randomly split into a derivation cohort (n = 814) and a validation cohort (n = 386). Logistic regression was used to examine the relation between risk factors and the occurrence of DE. To each covariate in the model was assigned an integer score based on the regression coefficients. Variables included in the risk score, according to multivariable analysis, were occlusion pattern of infarct-related artery, Thrombolysis In Myocardial Infarction Thrombus Score 2 to 4, reference vessel diameter ≥3.5 mm, and lesion length >20 mm. To each variable was assigned a 0- to +2-point score according to the strength of the statistical association. Rates of DE in low-, intermediate-, and high-risk groups were 5.6%, 15.8%, and 40% in the derivation cohort (p for trend <0.0001; C-statistic 0.70) and 7.5%, 12.1%, and 37.9% in the validation cohort (p for trend <0.0001; C-statistic 0.62), respectively. In conclusion, the individual risk of DE in patients who underwent p-PCI can be predicted using a simple 4-variables model based on angiographic features.