BACKGROUND: Right ventricular (RV)-arterial uncoupling is a powerful independent predictor of prognosis in heart failure with preserved ejection fraction (HFpEF). Coronary artery disease (CAD) can contribute to the pathophysiological characteristics of HFpEF. This study aimed to evaluate the prognostic value of RV-arterial uncoupling in acute HFpEF patients with CAD. METHODS: This prospective study included 250 consecutive acute HFpEF patients with CAD. Patients were divided into RV-arterial uncoupling and coupling groups by the optimal cutoff value, based on a receiver operating characteristic curve of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). The primary endpoint was a composite of all-cause death, recurrent ischemic events, and HF hospitalizations. RESULTS: TAPSE/PASP ≤0.43 provided good accuracy in identifying patients with RV-arterial uncoupling (area under the curve, 0.731; sensitivity, 61.4%; and specificity, 76.6%). Of the 250 patients, 150 and 100 patients could be grouped into the RV-arterial coupling (TAPSE/PASP >0.43) and uncoupling (TAPSE/PASP ≤0.43) groups, respectively. Revascularization strategies were slightly different between groups; the RV-arterial uncoupling group had a lower rate of complete revascularization (37.0% [37/100] vs . 52.7% [79/150], P <0.001) and a higher rate of no revascularization (18.0% [18/100] vs . 4.7% [7/150], P <0.001) compared to the RV-arterial coupling group. The cohort with TAPSE/PASP ≤0.43 had a significantly worse prognosis than the cohort with TAPSE/PASP >0.43. Multivariate Cox analysis showed TAPSE/PASP ≤0.43 as an independent associated factor for the primary endpoint, all-cause death, and recurrent HF hospitalization (hazard ratios [HR]: 2.21, 95% confidence interval [CI]: 1.44-3.39, P <0.001; HR: 3.32, 95% CI: 1.30-8.47, P = 0.012; and HR: 1.93, 95% CI: 1.10-3.37, P = 0.021, respectively), but not for recurrent ischemic events (HR: 1.48, 95% CI: 0.75-2.90, P = 0.257). CONCLUSION RV-arterial uncoupling, based on TAPSE/PASP, is independently associated with adverse outcomes in acute HFpEF patients with CAD.
Humans ; Prognosis ; Prospective Studies ; Stroke Volume/physiology* ; Echocardiography, Doppler/adverse effects* ; Coronary Artery Disease/complications* ; Heart Failure ; Pulmonary Artery/diagnostic imaging* ; Ventricular Function, Right/physiology* ; Ventricular Dysfunction, Right

OBJECTIVE: To explore the clinical and genetic characteristics of a child with Arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: A 6-year-old boy with ARVC who had visited Fujian Provincial Children's Hospital on August 23, 2022 was selected as the study subject. Relevant clinical data were collected, and peripheral venous blood samples were collected from the child and his parents for genetic testing through whole exome sequencing (WES). Sanger sequencing was carried out for family verification, and pathogenicity analysis was conducted for the candidate variants. RESULTS: The child had exhibited clinical symptoms including systemic edema, generalized heart enlargement, universal reduction of interventricular septum and ventricular wall movement, reduced left ventricular diastolic and systolic function, and reduced right ventricular systolic function. WES revealed that the child has harbored compound heterozygous variants of the PKP2 gene, namely c.119_122del (p.Leu40ArgfsTer71) and c.1978G>A (p.Gly660Arg), which were verified by Sanger sequencing to be respectively inherited from his father and mother. The c.119_122del variant has not been recorded in the 1000 Genomes, gnomAD and ExAC databases, and was predicted to lead to truncation of the PKP2 protein by SWISS-MODEL and PyMOL online software and classified as likely pathogenic based on the guidelines jointly developed by the American College of Medical Genetics and Genomics (ACMG) and ClinGen. The c.1978G>A variant has also not been recorded in the 1000 Genomes, gnomAD and ExAC databases, and was predicted to be deleterious by online software including REVEL, SIFT, CADD, Mutation Taster, and PolyPhen-2. The amino acid encoded by the variant site was highly conserved among various species by analysis using T-coffee and ESPript v3.0 online servers. The variant may affect the protein function by SWISS-MODEL and PyMOL online server analysis, and was classified as likely pathogenic based on the guidelines jointly developed by the ACMG and ClinGen. CONCLUSION The compound heterozygous variants of c.119_122del (p.Leu40ArgfsTer71) and c.1978G>A (p.Gly660Arg) of the PKP2 gene probably underlay the ARVC in this child. Above finding has broadened the spectrum of PKP2 gene variants and provided a reference for the diagnosis and genetic counseling.
Male ; Child ; Humans ; Arrhythmogenic Right Ventricular Dysplasia/genetics* ; Diastole ; Ethnicity ; Genetic Counseling ; Genetic Testing ; Plakophilins/genetics*

Objective: To investigate the histological features and clinical manifestations in different types of cardiac amyloidosis to improve diagnostic accuracy. Methods: The histopathological features and clinical manifestations of 48 patients diagnosed with cardiac amyloidosis by Congo red stain and electron microscopy through endomyocardial biopsy were collected in West China Hospital of Sichuan University from January 2018 to December 2021. Immunohistochemical stains for immunoglobulin light chains (κ and λ) and transthyretin protein were carried out, and a review of literature was made. Results: The patients age ranged from 42 to 79 years (mean 56 years) and the male to female ratio was 1.1 to 1.0. The positive rate of endomyocardial biopsy was 97.9% (47/48), which was significantly higher than that of the abdominal wall fat (7/17). Congo red staining and electron microscopy were positive in 97.9% (47/48) and 93.5% (43/46), respectively. Immunohistochemical stains showed 32 cases (68.1%) were light chain type (AL-CA), including 31 cases of AL-λ type and 1 case of AL-κ type; 9 cases (19.1%) were transthyretin protein type (ATTR-CA); and 6 cases (12.8%) were not classified. There was no significant difference in the deposition pattern of amyloid between different types (P>0.05). Clinical data showed that ATTR-CA patients had less involvement of 2 or more organs and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) than the other type patients (P<0.05). The left ventricular stroke volume and right ventricular ejection fraction of ATTR-CA patients were better than the other patients (P<0.05). Follow-up data of 45 patients was obtained, and the overall mean survival time was 15.6±2.0 months. Univariate survival analysis showed that ATTR-CA patients had a better prognosis, while cardiac amyloidosis patients with higher cardiac function grade, NT-proBNP >6 000 ng/L, and troponin T >70 ng/L had a worse prognosis (P<0.05). Multivariate survival analysis showed that NT-proBNP and cardiac function grade were independent prognostic factors for cardiac amyloidosis patients. Conclusions: AL-λ is the most common type of cardiac amyloidosis in this group. Congo red staining combined with electron microscopy can significantly improve the diagnosis of cardiac amyloidosis. The clinical manifestations and prognosis of each type are different and can be classified based on immunostaining profile. However, there are still a few cases that cannot be typed; hence mass spectrometry is recommended if feasible.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Prealbumin/metabolism* ; Stroke Volume ; Cardiomyopathies/pathology* ; Congo Red ; Ventricular Function, Right ; Amyloidosis/pathology* ; Prognosis

Objective: To evaluate the right ventricular function using two-dimensional speckle tracking echocardiography (2-D STE) and analyze the associated risk factors of right ventricular dysfunction in patients with silicosis. Methods: All 104 patients with silicosis treated in the Department of Occupational Medicine and Toxicology in Beijing Chao-Yang Hospital, Capital Medical University from May 2021 to September 2022 were enrolled in this study in October 2022. The clinical information of patients such as general data, arterial blood gas analysis and pulmonary function test were collected. The right ventricular function of patients was evaluated by 2-D STE-derived right ventricular free wall longitudinal strain (RVFWLS) and conventional echocardiographic-derived parameters, including right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) and doppler tissue imaging-derived tricuspid lateral annular systolic velocity (S'), respectively. Based on their RVFWLS, the patients were divided into right ventricular dysfunction group and normal right ventricular function group. Risk factors for right ventricular dysfunction in patients with silicosis were analyzed using binary logistic regression analysis. Results: A total of 104 silicosis patients were enrolled, with aneverage age (65.52±11.18) years old, among whom including 57 cases diagnosed with stage Ⅰ/Ⅱ silicosis and 47 cases diagnosed with stage Ⅲ silicosis. 26 (25.00%) patients concurrent right ventricular dysfunction. The abnormal rates of RVFAC, TAPSE and S' in patients were 16.35% (17 cases), 21.15% (22 cases) and 6.73% (7 cases), respectively. The RVFAC and TAPSE in right ventricular dysfunction group were lower than those in normal right ventricular function group, and the incidence of pulmonary arterial systolic pressure ≥36 mmHg was higher than that in normal right ventricular function group (P<0.05). Logistic regression analysis showed that arterial partial pressure of oxygen (OR=0.932, 95%CI: 0.885-0.981, P=0.007) was the protective factor, and the forced expiratory volume in 1 second (FEV(1)) /forced vital capacity (FVC) ratio<70% (OR=5.484, 95%CI: 1.049-28.662, P=0.044) and stage Ⅲ silicosis (OR=6.343, 95%CI: 1.698-23.697, P=0.007) were the risk factors for silicosis patients concurrent right ventricular dysfunction. Conclusion: The incidence of right ventricular dysfunction is higher in patients with stage Ⅲ silicosis than that in patients with stage Ⅰ/Ⅱ silicosis. Using 2-D STE can help the early detection of silicosis with right ventricular dysfunction. Hypoxemia, airflow limitation and the stage Ⅲ silicosis are the risk factors for silicosis patients concurrent right ventricular dysfunction.
Humans ; Middle Aged ; Aged ; Ventricular Dysfunction, Right/etiology* ; Ventricular Function, Right ; Echocardiography ; Risk Factors ; Silicosis/diagnostic imaging*

Arrhythmogenic Right Ventricular Dysplasia/genetics* ; Genotype ; Humans ; Phenotype ; Risk Assessment

OBJECTIVES: To study the association between hepatocyte growth factor (HGF) and treatment response in mice with hypoxic pulmonary arterial hypertension (HPAH) and the possibility of HGF as a new targeted drug for HPAH. METHODS: After successful modeling, the HPAH model mice were randomly divided into two groups: HPAH group and HGF treatment group (tail vein injection of recombinant mouse HGF 1 mg/kg), with 10 mice in each group. Ten normal mice were used as the control group. After 5 weeks, echocardiography was used to measure tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio; the Griess method was used to measure the content of nitric oxide in serum; ELISA was used to measure the serum level of endothelin-1; transmission electron microscopy was used to observe changes in the ultrastructure of pulmonary artery. RESULTS: Compared with the HGF treatment and normal control groups, the HPAH group had significantly higher tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio (P<0.05). The transmission electron microscopy showed that the HPAH group had massive destruction of vascular endothelial cells and disordered arrangement of the elastic membrane of arteriolar intima with rupture and loss. The structure of vascular endothelial cells was almost complete and the structure of arterial intima elastic membrane was almost normal in the HGF treatment group. Compared with the normal control and HGF treatment groups, the HPAH group had significantly higher serum levels of nitric oxide and endothelin-1 (P<0.05). CONCLUSIONS Increasing serum HGF level can alleviate the impact of HPAH on the cardiovascular system of mice, possibly by repairing endothelial cell injury, improving vascular remodeling, and restoring the normal vasomotor function of pulmonary vessels.
Animals ; Body Weight ; Endothelial Cells ; Endothelin-1 ; Hepatocyte Growth Factor/therapeutic use* ; Hypertrophy, Right Ventricular ; Hypoxia ; Mice ; Nitric Oxide ; Pulmonary Arterial Hypertension/drug therapy*

Ventricular Function, Right ; Heart Ventricles/diagnostic imaging* ; Echocardiography

Desmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels. DSP is essential for normal myocardial development and the maintenance of its structural functions. Studies have suggested that DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM), left ventricular noncompaction, and is also closely associated with the Carvajal syndrome, Naxos disease, and erythro-keratodermia-cardiomyopathy syndrome with skin and heart damage. The structure and function of DSP, as well as the clinical manifestations of DSP-related cardiomyopathy were reviewed in this article.
Arrhythmogenic Right Ventricular Dysplasia ; Cardiomyopathies/genetics* ; Desmoplakins/genetics* ; Hair Diseases ; Humans ; Keratoderma, Palmoplantar

Echocardiography, Three-Dimensional ; Funnel Chest/surgery* ; Humans ; Ventricular Dysfunction, Right/diagnostic imaging* ; Ventricular Function, Right

Right ventricular (RV) failure has become a deadly complication of left ventricular assist device (LVAD) implantation, for which desynchrony in bi-ventricular pulse resulting from a LVAD is among the important factor. This paper investigated how different control modes affect the synchronization of pulse between LV (left ventricular) and RV by numerical method. The numerical results showed that the systolic duration between LV and RV did not significantly differ at baseline (LVAD off and cannula clamped) (48.52%
Heart Failure/therapy* ; Heart-Assist Devices ; Humans ; Systole ; Ventricular Dysfunction, Right ; Ventricular Function, Right