To investigate the differences in clinical phenotypes between children and adult patient groups with left ventricular non-compaction (LVNC) and to evaluate the predictive efficacy of various biomarkers for ventricular arrhythmias (VAs) in LVNC. This study included 408 patients diagnosed with LVNC by cardiac magnetic resonance (CMR) between 2016 and 2023 (Children group < 18 years, n = 135; Adult group ≥ 18 years, n = 273). Baseline data, imaging parameters, and biomarkers were collected. Multivariable logistic regression analysis was used to identify independent predictors of VAs in LVNC. The optimal cut-off value for NT-proBNP was determined using receiver-operating characteristic (ROC) curve analysis. A restricted cubic spline model was constructed to analyze the dose-response relationship. Finally, VAs risk was assessed using tertile stratification and subgroup analysis. Compared with the children group, the adult group showed significantly reduced cardiac function (LVEF-CMR 40.72

BACKGROUND:Pediatric left ventricular non-compaction (LVNC) has a heterogeneous prognosis, with cardiovascular death as a major threat. This study explored predictive markers and aimed to construct a simplified risk stratification model. METHODS:In this multicenter longitudinal cohort study, 157 LVNC patients aged < 18 years were enrolled. Baseline data were collected. The primary endpoint was cardiovascular death. Independent predictors were identified by Cox regression, with significant indicators adjusted for body surface area (BSA) and stratified into tertiles. Restricted cubic splines, Kaplan-Meier survival curves, subgroup analyses, and ROC curves were employed to assess their predictive performance and robustness. RESULTS:The mean follow-up duration was 3.34 ± 2.86 years. Cardiovascular death occurred in 26 patients (16.6%). Left atrial diameter (LAD) (HR = 1.052, P = 0.046) and NT-proBNP (HR = 1.159, P = 0.039) were independent predictors. BSA-adjusted LAD/BSA showed improved prediction (AUC 0.702-0.768). Patients in the highest tertiles for LAD/BSA ( > 29.55 mm/m²; HR = 4.242) and NT-proBNP ( > 1362.40 pg/mL; HR = 1.720) had significantly increased risk, with a continuous positive dose-response relationship. Survival curves and subgroup analyses confirmed the robustness of these associations. CONCLUSION:LAD and NT-proBNP independently predict cardiovascular death in pediatric LVNC. A model using BSA-adjusted LAD/BSA and NT-proBNP tertiles can identify high-risk children, aiding early clinical risk stratification. IMPACT:Identifies left atrial diameter (LAD) and N-terminal pro B-type natriuretic peptide (NT‑proBNP) as independent predictors of cardiovascular death in pediatric left ventricular non‑compaction (LVNC). Demonstrates that body‑surface‑area‑adjusted LAD (LAD/BSA) significantly improves predictive performance over unadjusted LAD. Proposes a simplified, clinically accessible risk-stratification model using tertiles of LAD/BSA and NT-proBNP to identify high-risk children and guide individualized management. Reveals a continuous, positive dose-response relationship for both markers, with the rate of risk increase tending to flatten at higher levels. Shows consistent predictive value across key clinical subgroups, supporting the robustness of the findings.

Background: Left ventricular hypertrabeculation (LVHT), often also known as left ventricular non-compaction, describes a cardiac phenotype characterized by prominent trabeculae and deep intertrabecular recesses. Genetic background of LVHT remains poorly understood. Moreover, the clinical relevance of genetic variants in LVHT has not been well described. Aims: This study aimed to characterize the genetic structure of a large LVHT cohort and investigate the impact of underlying genotype on clinical features and outcomes. Methods: Unrelated subjects with a cardiac magnetic resonance (CMR) - confirmed diagnosis of LVHT from four tertiary hospitals in China between 2010 and 2023 were prospectively included. Diagnosis of LVHT necessitated both the following CMR criteria: 1) long-axis (end-diastolic): a noncompacted (NC) /compacted(C) ratio >2.3 in ≥1 LV segments; 2) short-axis (end-diastolic): a NC/C ratio ≥3 in ≥1 of segments 1–3/7-16, or a NC/C ratio ≥2 in ≥1 of segments 4-6. Whole exome sequencing was conducted in all subjects. Primary endpoint was a composite of major adverse cardiovascular events (MACE). Cox proportional hazards model was used in statistical analysis. Results: A total of 406 subjects diagnosed with LVHT were included in the study. The median age at diagnosis was 38 years (IQR 26-52), with 67% males and 88% adults. Overall, 136 pathogenic (P) or likely pathogenic (LP) variants were found in 125 subjects (30.8%). TTN (13.8%) was the most common gene, followed by MYH7 (2.9%) and MYBPC3 (2.5%) (Figure 1). Subjects presented with at least 9 sub-phenotypes, the dilated being the most prevalent type (69.2%), followed by the benign type (7.4%), the hypertrophic type (5.7%), LVHT with congenital cardiovascular malformations (5.7%) (Figure 2A). TTN (19%) was the most prevalent gene identified in the dilated group, MYH7 and MYBPC3 (14%) were the most prevalent genes in the hypertrophic group (Figure 2B). During a median follow-up of 35.7 months, combined covariate analysis revealed that genotype-positive status was independently associated with MACE (HR: 1.69; 95% CI: 1.12-2.56; P =0.013) (Figure 3). Conclusions: LVHT possesses a heterogeneous nature, exhibiting diverse genetic and phenotypic profiling. Subjects with LVHT carrying P/LP variants have worse prognosis. Therefore, genetic testing may contribute to prognostic stratification and management guidance in these subjects.

There is an increased risk of diabetes and cardiovascular disease among patients with psoriasis. However, whether diabetes affects the cardiovascular adverse events in patients with psoriasis who have suffered from coronary artery disease remains unclear. This study aimed to explore the prognostic role of diabetes in this particular population. This single-center, retrospective cohort study included all consecutive adult patients with psoriasis and coronary artery disease admitted at our hospital between January 2017 and May 2022. Clinical records were collected and compared between patients with and without diabetes. Survival curves were derived using Kaplan–Meier methods. Multivariable Cox regression was used to control potential confounding. This study included 305 participants, including 147 patients (48.2

Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in SCNN1A, SCNN1B or SCNN1G, which respectively encode the alpha, beta and gamma subunits of the epithelial sodium channel. In the present study, DNA was extracted from leukocytes in peripheral blood obtained from all members of a family with Liddle syndrome. Whole-exome sequencing and Sanger sequencing were performed to assess the candidate variant and a co-segregation analysis was conducted. A frameshift mutation in SCNN1B (NM_ 000336: c.1806dupG, p.Pro603Alafs*5) in the family was identified, characterized by early-onset hypertension and hypokalemia. The mutation led to the truncation of the beta subunit of the epithelial sodium channel and a lack of the conservative PY motif. Furthermore, a systematic review of follow-up data from patients with Liddle syndrome with SCNN1B mutations was performed. The follow-up data of 108 patients with pathogenic SCNN1B mutations from 47 families were summarized. Phenotypic heterogeneity was evident in patients with Liddle syndrome and early-onset hypertension was the most frequent symptom. Patients responded well to targeted amiloride therapy with significant improvements in blood pressure and serum potassium concentration. The present study demonstrates that confirmatory genetic testing and targeted therapy can prevent premature onset of clinical endpoint events in patients with Liddle syndrome.

Introduction: Neurofibromatosis type 1 (NF-1) is caused by mutations in the NF1 gene that encodes neurofibromin, a negative regulator of RAS proto-oncogene. Approximately one-third of the reported pathogenic mutations in NF1 are splicing mutations, but most consequences are unclear. The objective of this study was to identify the pathogenicity of splicing mutation in a Chinese family with NF-1 and determine the effects of the pre-mRNA splicing mutation by in vitro functional analysis. Methods: Next-generation sequencing was used to screen candidate mutations. We performed a minigene splicing assay to determine the effect of the splicing mutation on NF1 expression, and three-dimensional structure models of neurofibromin were generated using SWISS-MODEL and PROCHECK methods, respectively. Results: A pathogenic splicing mutation c.479+1G>C in NF1 was found in the proband characterized by childhood-onset refractory hypertension. In vitro analysis demonstrated that c.479+1G>C mutation caused the skipping of exon 4, leading to a glutamine-to-valine substitution at position 97 in neurofibromin and an open reading frame shift terminating at codon 108. Protein modeling showed that several major domains were missing in the truncated neurofibromin protein. Conclusion: The splicing mutation c.479+1G>C identified in a Chinese patient with NF-1 and childhood-onset refractory hypertension caused the skipping of exon 4 and a truncated protein. Our findings offer new evidence for the molecular diagnosis of NF-1.

Objective: Liddle syndrome is an autosomal dominant form of monogenic hypertension caused by mutation of the SCNN1A, SCNN1B, and SCNN1G genes, which respectively encode various subunits of the epithelial sodium channel. In this report, we describe a frameshift mutation in SCNN1B in a Chinese family with early-onset hypertension and hypokalemia. Design and method: DNA was extracted from leucocytes in peripheral blood obtained from all family members. Whole-exome sequencing and Sanger sequencing were performed to verify the candidate variant and conduct co-segregation analysis. We also reviewed the clinical and biochemical characteristics of patients with the same mutation described in the literature and performed a genotype–phenotype correlation analysis. Results: Whole-exome sequencing identified a c.1806dupG frameshift variant in SCNN1B leading to substitution of alanine for proline at position 603 and premature emergence of a stop codon at position 607. Phenotypic heterogeneity is evident in patients with the mutation reported in the literature and is reflected in the proportions with hypertension (94.4%), hypokalemia (58.9%), hypoaldosteronemia (52.9%), and hyporeninemia (41.1%). Patients with the mutation have a good response to targeted ENaC inhibitor therapy. Conclusions: We have identified a frameshift mutation (c.1806dupG) in SCNN1B in a Chinese family characterized by early-onset hypertension and hypokalemia. Confirmatory genetic testing is necessary and targeted therapy should be used to prevent premature onset of clinical endpoints events in patients suspected to have mutation. Genotype-phenotype correlation analysis involving the P603 residue variant provides further evidence of phenotypic heterogeneity and guidance for clinical management of Liddle syndrome.

Background: Psoriasis is associated with an increased prevalence of cardiovascular risk factors, including metabolic syndrome (MetS). To date, it is unclear whether MetS causes differences in cardiovascular outcomes in psoriatic patients with coronary artery disease. Methods: We conducted a retrospective cohort study to determine the effects of MetS in psoriatic patients with coronary artery disease. Comparisons were made between patients with and without MetS. Cox regression analysis and Kaplan-Meier survival analysis were used to evaluate the association between variables.Results: Of the 307 psoriatic patients with coronary artery disease, 94 met criteria (30.6%) for MetS. Individuals with MetS were more likely to be female (p <0.001). Levels of platelet counts and high-sensitivity C-reactive protein were higher in the MetS group (p = 0.038 and 0.005, respectively). After a mean follow-up of 35.32 months, major adverse cardiovascular events (MACEs) and non-fatal myocardial infarction were more likely in the MetS than the non-MetS group (33.3% vs 20.6%, p = 0.02; 26.4% vs 15.7%, p = 0.032, respectively). Kaplan-Meier estimates showed the same trend. Cox regression analysis showed that MetS (hazard ratio 1.738; 95% confidence interval 1.045-2.891; p = 0.033) and left ventricular ejection fraction (hazard ratio 0.968; 95% confidence interval 0.945-0.991; p = 0.006) were associated with an increased risk of MACEs.Conclusion: In psoriatic patients with coronary artery disease, MetS independently predicted MACEs. In addition, left ventricular ejection fraction was negatively associated with an increased risk of MACEs. To reduce the cardiovascular disease risk, it is necessary to increase awareness of MetS in psoriatic patients with coronary artery disease.

Hypertension is a cardiovascular disease that seriously threat-ens public health worldwide.Early and effective control of blood pressure can prevent the occurrence of stroke,coronary heart dis-ease,kidney disease,etc.[1,2].The influence of genetic factors on hypertension has been confirmed multiple times,and targeted medication according to genetic testing remains a challenge for hypertension treatment at present[3].

Background The prognostic value of lipoprotein (Lp) (a) in patients who have suffered from coronary artery disease (CAD) has not been fully studied, and the results are inconsistent. This study was conducted to evaluate whether increased Lp(a) concentrations cause differences in clinical adverse outcomes in patients with psoriasis who have already suffered from CAD. Methods This retrospective cohort study included consecutive patients with psoriasis and CAD between January 2017 and May 2022 in our hospital. The clinical records were collected, and comparisons were made between patients in the low Lp(a) and high Lp(a) groups. Cox proportional hazard analysis and log-rank tests were used to evaluate the association between variables. Results Among 295 patients, 148 patients were in the low Lp(a) group, and 147 were in the high Lp(a) group. These two groups did not differ significantly in age, gender or body mass index. Compared with the low Lp(a) group, the levels of platelet counts ( P = 0.038) and high sensitivity C reactive protein ( P = 0.012) were higher in the high Lp(a) group. Patients in the high Lp(a) group had higher total cholesterol levels ( P = 0.029) and lower triglyceride levels ( P = 0.037). Among the whole cohort, clinical adverse events were not correlated with Lp(a) concentrations after a median follow-up of 3 years. However, in the subgroup analysis, there were significant differences in all-cause death (log rank P = 0.036) and rehospitalization (log rank P = 0.037) between the two groups in patients with diabetes; a difference in rehospitalization (log rank P = 0.042) was also found between the two groups in men. Conclusions In patients with psoriasis and CAD, high levels of Lp(a) were related to a poor prognosis, especially in patients with diabetes and in men. These results will provide valuable information for the risk stratification of patients with psoriasis and CAD.

Objective: Psoriasis is associated with a heightened prevalence of cardiovascular risk factors, including diabetes. However, it is not clear whether diabetes will cause differences on clinical outcomes of psoriatic patients who have already suffered from coronary artery disease. Design and method: We conducted a retrospective cohort study of consecutive psoriatic patients with coronary artery disease between January 2017 and May 2022 in our hospital. The clinical records, laboratory measurements and coronary angiography reports were collected, and comparisons were made between patients with and without diabetes. The Cox regression analysis and Kaplan-Meier survival analysis were used to evaluate the association between diabetes and major adverse cardiovascular events (MACEs). Results: Of the 307 participants, 147 patients had diabetes. Individuals with diabetes were more prone to be with hypertension (p = 0.045), history of stroke (p = 0.041) and peripheral vascular disease (p = 0.043). The levels of low-density lipoprotein cholesterol (p = 0.039), uric acid (p = 0.013) and homocysteine (p = 0.006) were higher in the non-diabetes group. Patients with diabetes were more likely to have lesions in the right coronary artery than those without diabetes(p = 0.03). After the mean follow-up of 35.32 ± 18.61 months, MACEs were more prone to occur in diabetes group than non-diabetes group (30.0% vs. 19.2%, p = 0.032). Kaplan-Meier estimates showed the same trend. The COX regression analysis showed that diabetes [hazard ratio (HR) = 1.661, 95% confidence interval (95%CI): 1.025–2.692, p = 0.039] was positively associated with an increased risk of MACEs. In the subgroup analysis, diabetes was associated with the occurrence of MACEs especially in men (p = 0.008) and in patients without chronic kidney disease(p = 0.021). Conclusions: In psoriatic patients with coronary artery disease, patients with diabetes were more likely to have lesions in the right coronary artery and diabetes can independently predict MACEs, especially in men and in patients without chronic kidney disease. To reduce the cardiovascular disease risk associated with diabetes, it is vital to increase awareness of the condition among these patients.

Purpose:The presence of elevated fibrinogen levels is associated with cardiovascular disease. However, whether fibrinogen level is associated with adverse clinical events in patients with psoriasis and coronary artery disease (CAD) is unknown. This study aimed to investigate the relationship between fibrinogen levels and cardiovascular adverse events in these patients.Patients and Methods:This retrospective cohort study collected consecutive patients with psoriasis and CAD between January 2017 and May 2022 in our hospital. The clinical records were collected, and comparisons were made between groups. The Cox regression analysis and Kaplan-Meier survival analysis were used to evaluate the association between variables.Results:Of the 267 participants, one hundred and forty-seven patients (55.1%) had elevated fibrinogen levels. Compared with patients in low fibrinogen group, white blood cell and platelet counts and high-sensitivity C-reactive protein levels were higher, whereas the left ventricular ejection fraction was lower in patients in high fibrinogen group. After a median follow-up of 35.5 months, the incidence of major adverse cardiovascular events (MACEs) was higher in patients in high fibrinogen group compared with patients in low fibrinogen group (31.4% vs 16.4%, p = 0.013). The Kaplan-Meier survival curves showed the same trend (log rank p = 0.020). Subgroup analysis revealed a positive association between elevated fibrinogen levels and MACEs in patients aged <60 years (log-rank p = 0.013), those with diabetes (log-rank p = 0.027), and those who were not admitted for acute cardiovascular syndrome (log-rank p = 0.015).Conclusion:Elevated fibrinogen levels were associated with adverse clinical events in patients with psoriasis and CAD, especially among patients aged <60 years, those with diabetes, and those not admitted for acute cardiovascular syndrome.

To evaluate the potential predictive value of total bilirubin (TBIL) for one-year prognosis in patients with coronary artery disease (CAD) and psoriasis. 278 psoriasis patients who underwent coronary angiography and were diagnosed as CAD were recruited. Baseline TBIL was measured at admission. Patients were divided into three groups according to the third tertiles of TBIL. The coronary angiography showed that lower TBIL was associated with the severity of lesion calcification. After a mean follow-up of 315 days, major adverse cardiac and cerebrovascular events (MACCEs) were reported in 61 patients. Compared with patients with higher TBIL tertiles, the incidence of MACCEs increased significantly in patients with middle and lower TBIL tertiles. The incidence of MACCEs in one-year follow-up was significantly different between higher and lower tertiles. The findings indicate that decreased TBIL is a potential predictor of poor prognosis in patients with psoriasis and CAD.

Objective: Neurofibromatosis type 1 (NF-1) is caused by mutations in the NF1 gene that encodes neurofibromin, a negative regulator of RAS proto-oncogene. Approximately one-third of the reported pathogenic mutations in NF1 are splicing mutations, suggesting that splicing mutations are not rare. The objective of this study was to identify the pathogenicity of splicing mutation in a Chinese family with NF-1 and determine the effects of the pre-mRNA splicing mutation by in vitro functional analysis. Design and method: Next-generation sequencing was used to screen candidate mutations and Sanger sequencing was performed for validation. We performed a minigene splicing assay to determine the effect of the splicing mutation on NF1 expression and three-dimensional structure models of wild-type and mutant-type neurofibromin were generated using SWISS-MODEL and PROCHECK method, respectively. Results: Next-generation sequencing analysis identified a pathogenic splicing mutation c.479 + 1G>C in NF1 in the proband who had typical pigmental lesions and severe renal artery hypertension. We speculated that the causative mutation originated from the proband's mother who died of glioma. The minigene splicing assay showed that the c.479 + 1G>C mutation caused the skipping of exon 4, leading to a Glutamine to Valine substitution at position 97 in neurofibromin and an open reading frame shift terminating at codon 108. Three-dimensional modelling of neurofibromin showed that several major domains were missing in the truncated protein, which would have affected its function. Conclusions: The splicing mutation c.479 + 1G>C identified in a Chinese pedigree with NF-1 caused the skipping of exon 4 and resulted in a truncated protein. Our findings would be of great significance for the molecular diagnosis and management of NF-1 and showed that the minigene splicing assay is a powerful tool for analyzing mRNA expression outcomes caused by donor splicing site variation.

Background Sengers syndrome characterized by hypertrophic cardiomyopathy is an extremely rare genetic disorder. Sengers syndrome associated with left ventricular non-compaction (LVNC) has not been described. Methods Genetic testing was used to identify candidate AGK variants in the proband. The predicted molecular structures were constructed by protein modeling. Exon skipping caused by the identified splicing mutations was verified by in silico analyses and in vitro assays. The genotypic and phenotypic features of patients with AGK splicing mutations were extracted by a systematic review. Results The proband was characterized by Sengers syndrome and LVNC and caused by a novel compound heterozygous AGK splicing mutation. This compound mutation simultaneously perturbed the protein sequences and spatial conformation of the acylglycerol kinase protein. In silico and in vitro analyses demonstrated skipping of exons 7 and 8 and premature truncation as a result of exon 8 skipping. The systematic review indicated that patients with an AGK splicing mutation may have milder phenotypes of Sengers syndrome. Conclusions The genotypic and phenotypic spectrums of Sengers syndrome have been expanded, which will provide essential information for genetic counseling. The molecular mechanism in AGK mutations can offer insights into the potential targets for treatment. Impact First description of a child with Sengers syndrome and left ventricular non-compaction cardiomyopathy. A novel pathogenic compound heterozygous splicing mutation in AGK for Sengers syndrome was identified. The identified mutations led to exons skipping by in silico analyses and in vitro assays.

Objective: In recent years, there has been a lot of controversy about the factors affecting the penetrance of multiple endocrine neoplasia type 2A(MEN2A). Some studies considered it may be related to gene mutations. In the present study, we aimed to support the hypothesis that RET gene mutation affect the penetrance of MEN2A and study the effects of novel SLC12A3 variants in MEN2A. Design and method: Peripheral blood samples were collected from the proband and his relatives. Whole-exome sequencing and Sanger sequencing were performed to identify the gene mutations. The protein structure prediction with comparative modelling was used to predict the effects of novel gene variants on protein function. We also used the clinical examinations to evaluate the phenotypes of patients comprehensively. Results: Genetic analysis identified RET c.1901G>A and novel variants in SLC12A3 c.3070_3079delinsCAG in the proband and his mother. The patients carrying the novel SLC12A3 variants didn’t show the typical clinical manifestations of Gitelman syndrome because of heterozygosity. But it is theoretically explained that the novel variants of SLC12A3 may affect the function of protein. We also found SLC12A3 gene was not expressed in typical target organs of MEN2A.We are the first to describe compound RET c.1901G>A and SLC12A3 mutations in one family with MEN2A. Our study supports the hypothesis that RET gene mutations affect the penetrance of MEN2A. The novel variants in SLC12A3 may be disease causing, but it is not significantly related to the clinical phenotype of MEN2A in our study. Conclusions: RET gene mutation affect the penetrance of MEN2A. The novel variants in SLC12A3 may affect the function of protein, but it is not significantly related to the clinical phenotype of MEN2A.We need more studies about the phenotypes and related mechanisms of gene mutations to guide individual treatment.