OBJECTIVES: Early detection of asymptomatic diastolic dysfunction is essential to prevent the development of heart failure in hypertensive patients. Current studies suggest that left atrial strain contributes to the evaluation of left ventricular diastolic function, but there are fewer studies on the correlation between left atrial strain and diastolic function in hypertensive patients. In this study, we applied a two-dimensional speckle tracking technique to evaluate the changes in left atrial strain in hypertensive patients, and to investigate the relationship between left atrial strain and left ventricular diastolic function. METHODS: A total of 82 hypertensive patients who were visited the Department of Cardiology at the Third Xiangya Hospital of Central South University from July 2021 to January 2022, were enrolled for this study, and 59 healthy subjects served as a control group. According to the number of left ventricular diastolic function indexes recommended by the 2016 American Society of Echocardiography Diastolic Function Guidelines (mitral annular e´ velocity: Septal e´<7 cm/s, lateral e´<10 cm/s, E/e´ ratio>14, left atrial volume index>34 mL/m², peak tricuspid regurgitation velocity>2.8 m/s), the hypertensive patients were divided into 3 groups: Group Ⅰ (0 index, n=36 ), Group Ⅱ (1 index, n=39), and Group Ⅲ (2 indexes, n=7). Two-dimensional speckle tracking technique was used to measure left atrial reservoir strain (LASr), conduit strain, and contraction strain, and to analyze the correlation between left atrial strain and left ventricular diastolic function in hypertensive patients. RESULTS: The LASr, left atrial conduit strain (LAScd), and LASr/(E/septal e´) of the hypertension group were lower than those of the control group, and E/LASr was higher than that of the control group. There was no significant difference in left atrium volume index between the 2 groups (P>0.05). Compared with Group Ⅰ, LASr, LAScd, and LASr/(E/septal e´) were decreased in Group Ⅱ and Group Ⅲ, LASr/(E/septal e´) was also decreased in Group Ⅲ compared with Group Ⅱ (all P<0.05). Compared with Group Ⅰ, E/LASr was increased in Group Ⅲ. LASr was positively correlated with septal e´, lateral e´, E, and E/A, and negatively correlated with E/septal e´. CONCLUSIONS The changes of left atrial function in patients with early hypertension are earlier than those of left atrial structure. Left atrial strain and its combination with conventional ultrasonographic indices [LASr/(E/septal e´)] of diastolic function are potentially useful in assessing left ventricular diastolic function in hypertensive patients.
Humans ; Atrial Fibrillation ; Atrial Appendage ; Heart Atria/diagnostic imaging* ; Hypertension/complications* ; Diastole

OBJECTIVE: To analyze the clinical and genetic characteristics of a child with restricted cardiomyopathy (RCM) and phenylketonuria (PKU), and summarize the clinical characteristics and genetic diversity of RCM in children through a literature review. METHODS: A child with RCM in conjunct with PKU who was admitted to the Children's Hospital Affiliated to Zhengzhou University in June 2020 due to edema of eyelids and lower limbs for 1 year and aggravation for over 1 month was selected as the study subject. Relevant clinical data were collected. Peripheral blood samples of the child and his parents were collected for whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing and bioinformatic analysis. Childhood, TNNI3 gene and restricted cardiomyopathy were used as the keywords to search the Wanfang data knowledge service platform, Chinese Journal Full-text database and PubMed database, and the search period was limited to from the time of establishment till August 2022. Clinical manifestations and characteristics of the TNNI3 gene variants were summarized. RESULTS: The child, a 2-year-old-and-4-month-old male, had normal intelligence, facial features and normal hair and skin color, but his motor and physical development was delayed, in addition with edema of bilateral eyelids and lower limbs. The results of WES and Sanger sequencing revealed that he has harbored compound heterozygous variants of the PAH gene, namely c.331C>T (p.R111X) and c.940C>A (p.P341T), which were inherited from his father and mother, respectively. In addition, he has also harbored a de novo heterozygous variant of c.508C>T (p.R170W) of the TNNI3 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the TNNI3: c.508C>T (p.R170W) was classified as a pathogenic variant (PS2+PS4+PM2_Supporting+PM5), PAH: c.331C>T (p.R111X) as a pathogenic variant (PVS1+PM2_Supporting+PM3+PP4), and c.940C>A (p.P341T) as a likely pathogenic variant (PM2_Supporting+PM3+PM5+PP4). In total 30 children with RCM caused by TNNI3 gene variants were retrieved, with a male-to-female ratio of 1 : 1.55 and manifestations including heart failure, sinus rhythm, bi-atrial enlargement, ST-T wave change, ventricular restricted filling, and decreased ventricular diastolic function. In total 16 variants of the TNNI3 gene were identified, among which c.575G>A was the most common, and all cases had conformed to an autosomal dominant inheritance. CONCLUSION Phenylalanine hydroxylase deficiency and RCM are rare diseases with complex clinical manifestations. The PAH: c.331C>T (p.R111X)/c.940C>A (p.P341T) and TNNI3: c.508C>T (p.R170W) variants probably underlay the RCM and PKU in this child.
Humans ; Male ; Cardiomyopathy, Restrictive ; Computational Biology ; Diastole ; Mutation ; Phenylketonurias ; Child, Preschool

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*

Autoimmune Diseases ; Diastole ; Humans ; Uric Acid ; Ventricular Dysfunction, Left ; Ventricular Function, Left

The implantation of biventricular assist device (BiVAD) is more challenging than that of left ventricular assist device for the interaction in the process of multiple input and output. Besides, ventricular assist device (VAD) often runs in constant speed (CS) mode in clinical use and thus BiVAD also faces the problems of low pulsation and imbalance of blood volume between systemic circulation and pulmonary circulation. In this paper, a delay assist mode for a VAD by shortening the support time of VAD was put forward. Then, the effect of the delay mode on cardiac output, pulsation and the function of the aortic valve was observed by numerical method and the rules of hemodynamics were revealed. The research showed that compared with VAD supported in CS mode, the VAD using delay mode in systolic and diastolic period proposed in this paper could meet the demand of cardiac output perfusion and restore the function of the arterial valves. The open ratio of aortic valve (AV) and pulmonary valve (PV) increased with the time set in delay mode, and the blood through the AV/PV helped to balance the left and the right cardiac volume. Besides, delay mode also improved the pulsation index of arterial blood flow, which is conducive to the recovery of the ventricular pulse function of patients.
Cardiovascular System ; Diastole ; Heart Failure ; Heart Rate ; Heart-Assist Devices ; Hemodynamics ; Humans ; Models, Cardiovascular

Auscultation of heart sounds is an important method for the diagnosis of heart conditions. For most people, the audible component of heart sound are the first heart sound (S1) and the second heart sound (S2). Different diseases usually generate murmurs at different stages in a cardiac cycle. Segmenting the heart sounds precisely is the prerequisite for diagnosis. S1 and S2 emerges at the beginning of systole and diastole, respectively. Locating S1 and S2 accurately is beneficial for the segmentation of heart sounds. This paper proposed a method to classify the S1 and S2 based on their properties, and did not take use of the duration of systole and diastole. S1 and S2 in the training dataset were transformed to spectra by short-time Fourier transform and be feed to the two-stream convolutional neural network. The classification accuracy of the test dataset was as high as 91.135%. The highest sensitivity and specificity were 91.156% and 92.074%, respectively. Extracting the features of the input signals artificially can be avoid with the method proposed in this article. The calculation is not complicated, which makes this method effective for distinguishing S1 and S2 in real time.
Diastole ; Heart ; Heart Sounds ; Neural Networks, Computer ; Rivers

This study aims to explore the intraventricular pressure difference (IVPD) within left ventricle in patients with paroxysmal atrial fibrillation (PAF) by using the relative pressure imaging (RPI) of vector flow mapping (VFM). Twenty patients with paroxysmal atrial fibrillation (PAF) and thirty control subjects were enrolled in the study. Systolic and diastolic IVPD derived from VFM within left ventricle and conventional echocardiographic parameters were analyzed. It was found that the B-A IVPD of left ventricle in PAF patients showed the same pattern as controls-single peak and single valley during systole and double peaks and double valleys during diastole. Basal IVPD was the main component of base to apex IVPD (B-A IVPD). The isovolumetric systolic IVPD was associated with early systolic IVPD, early systolic IVPD was associated with late systolic IVPD, and late systolic IVPD was associated with isovolumic diastolic IVPD (all
Atrial Fibrillation/diagnostic imaging* ; Diastole ; Heart Ventricles ; Humans ; Ventricular Function, Left ; Ventricular Pressure

diastole, and vessel compression index) on CCTA associated with CT-FFR ≤ 0.80 were analyzed. Receiver operating characteristic analysis was performed to describe the diagnostic performance of CT-FFR ≤ 0.80 in detecting interarterial R-ACAOS.RESULTS: Significant differences were found in proximal vessel morphology, take-off level, intramural course, % proximal narrowing area, and MLA at diastole (all p < 0.05) between the normal and abnormal CT-FFR groups. Take-off level, intramural course, and slit-like ostium (all p < 0.05) predicted hemodynamic abnormality (CT-FFR ≤ 0.80) with accuracies of 0.69, 0.71, and 0.81, respectively. Patients with CT-FFR ≤ 0.80 had a higher prevalence of typical angina (29.4% vs. 7.8%, p = 0.025) and atypical angina (29.4% vs. 6.5%, p = 0.016).CONCLUSION: Take-off level, intramural course, and slit-like ostium were the main predictors of abnormal CT-FFR values. Importantly, patients with abnormal CT-FFR values showed a higher prevalence of typical angina and atypical angina, indicating that CT-FFR is a potential tool to gauge the clinical relevance in patients with interarterial R-ACAOS.]]>
Angiography ; Coronary Sinus ; Coronary Vessel Anomalies ; Coronary Vessels ; Diastole ; Hemodynamics ; Humans ; Phenobarbital ; Prevalence ; Retrospective Studies ; ROC Curve ; Systole

BACKGROUND AND OBJECTIVES: Beta-blockers are indicated in patients with heart failure (HF) with reduced ejection fraction. However, their efficacy in patients with HF with preserved ejection fraction (HFpEF) is uncertain. We investigated the hypothesis that beta-blockers are associated with reduced adverse events in patients with HFpEF. METHODS: The Korea Acute Heart Failure (KorAHF) is a prospective observational multicentre cohort study. The 5,625 patients hospitalized for acute HF syndrome in 10 tertiary university hospitals across the country have been consecutively enrolled between March 2011 and February 2014. Of these patients, 2,152 patients with HFpEF (ejection fraction ≥40%) were investigated. The primary outcome was all-cause mortality according to beta-blocker use. RESULTS: During a median follow-up duration of 807 days, 702 patients died. In Cox proportional hazards model beta-blocker use was associated with a 14% reduced all-cause death (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75–0.98), but not with reduce rehospitalization (HR, 1.03; 95% CI, 0.85–1.27). In the propensity-score matched population, beta-blockers were also associated with reduced all-cause death (HR, 0.80; 95% CI, 0.69–0.94) but not with reduced rehospitalization (HR, 1.08; 95% CI, 0.87–1.33). CONCLUSIONS: In Korean patients with HFpEF, use of beta-blockers is associated with reduced all-cause death but not with reduced rehospitalization.
Cohort Studies ; Diastole ; Follow-Up Studies ; Heart Failure ; Heart ; Hospitals, University ; Humans ; Korea ; Mortality ; Proportional Hazards Models ; Prospective Studies

Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with IC₅₀ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect I(Na), I(Ks) or I(K1), but decreased I(hERG) in a dose-dependent manner (IC₅₀: 6.53 µM). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to 3 µM, but it at 10 µM induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.
Action Potentials ; Animals ; Antineoplastic Agents ; Aurora Kinases ; Cardiotoxicity ; Cell Division ; Cell Line ; Humans ; In Vitro Techniques ; Ion Channels ; Muscle Cells ; Myocardial Contraction ; Myocytes, Cardiac ; Phosphotransferases ; Rats ; Relaxation