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1.
Article in English | MEDLINE | ID: mdl-38709352

ABSTRACT

The data on myocardial perfusion of the percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for obstructive hypertrophic cardiomyopathy (HOCM) are still lacking, although PIMSRA have been proved to be of great safety and efficacy. The aim of this study was to quantitatively analyze the changes in myocardial perfusion after PIMSRA using myocardial contrast echocardiography (MCE). 27 HOCM patients treated with PIMSRA were retrospectively analyzed, and their echocardiographic parameters and perfusion parameters of MCE were collected before and 12 months after PIMSRA. A reperfusion curve was used to quantify microvascular blood volume (A), microvascular flux rate (ß), and microvascular blood flow (MBF) of each segment. Then the value difference (Δ) of parameters between post- and pre-operation were calculated. Finally, the correlation between the changes in MBF and in each echocardiographic parameter was analyzed. (1) Compared with baseline, the global A, ß and MBF were significantly increased in HOCM patients after PIMSRA (all P < 0.001). The ß, MBF were increased in the interventricular septum (P < 0.001, respectively), and the A, ß, MBF were increased in the left ventricular wall (all P < 0.001). (2) Correlation analysis showed that the ΔMBF of interventricular septum was mainly negatively correlated with the maximum interventricular septum thickness (ΔIVSTmax, r=-0.670, P < 0.001), mean interventricular septum thickness (ΔIVSTmean, r=-0.690, P < 0.001), and left ventricular mass index (ΔLVMI, r=-0.774, P < 0.001), while the ΔMBF of left ventricular wall was positively correlated with left ventricular end-diastolic volume index (ΔLVEDVI, r = 0.621, P = 0.001) and stroke volume index (ΔSVI, r = 0.810, P < 0.001). Myocardial perfusion was improved at both interventricular septum and ventricular wall in HOCM patients after PIMSRA. MCE can provide a new dimension for the efficacy evaluation to PIMSRA procedure.

2.
Eur Heart J Case Rep ; 8(4): ytae145, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38590297

ABSTRACT

Background: Some patients with hypertrophic cardiomyopathy (HCM) re-occur with drug-refractory symptoms but are not eligible for re-operation after the Morrow procedure. Traditional treatment options are limited. We present the first case of the use of ultrasound-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for the treatment of a patient with HCM combined with congenital anatomically corrected malposition of the great arteries (MGA) after Morrow procedure. Case summary: A 61-year-old male patient with congenital MGA, who had been treated with the Morrow procedure for HCM, had worsening symptoms in recent years that were difficult to control medically. He was diagnosed with occult obstructive HCM by stress echocardiography. After multi-disciplinary discussion, this patient was treated with PIMSRA. The post-operative clinical outcome was remarkable, with a significant decrease in septal thickness and disappearance of the left anterior branch conduction block. Conclusion: Percutaneous intramyocardial septal radiofrequency ablation is feasible and can be one of the options for the treatment of patients with HCM, especially those who cannot choose Morrow procedure. However, it still needs a large sample of clinical trials to validate its clinical effectiveness.

3.
Heart ; 110(11): 792-799, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38388470

ABSTRACT

OBJECTIVE: The objective is to evaluate the 5-year follow-up results of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) for hypertrophic obstructive cardiomyopathy (HOCM), including clinical status, electrocardiographic and echocardiographic characteristics. METHODS: 27 patients (age: 44.3±15.5 years; 67% men, 33% women) with severely symptomatic HOCM who underwent PIMSRA from October 2016 to September 2017 were included. Their clinical status, resting and exercise stress echocardiography, electrocardiography and cardiac MRI (CMRI) after long-term follow-up were assessed. RESULTS: One patient died of intracerebral haemorrhage 1 year post procedurally. The New York Heart Association class, Canadian Cardiovascular Society class and exercise-induced syncopal attacks improved significantly in 26 patients (all p<0.01). Left ventricular (LV) outflow tract gradients revealed sustained reduction (resting: from 95.0 to 9.0 mm Hg, p<0.001; post exercise: from 130.5 to 21.0 mm Hg, p<0.001). The echocardiographic evaluation revealed decreased septal thickness, LV posterior wall thickness and left atrial (LA) diameter (all p<0.001). CMRI data revealed decrease in LV mass index and LA volume index and increase in LV end-diastolic volume index and stroke volume index between baseline and long-term follow-up (all p<0.05). The global longitudinal strain of LV improved from (-11.9%±3.7%) before the procedure to (-13.1%±3.9%) at the last check (p<0.001). Malignant ventricular arrhythmia and heart failure events were not observed. CONCLUSIONS: PIMSRA can effectively alleviate symptoms in patients with HOCM and improve their hemodynamics in the long term. TRIAL REGISTRATION NUMBER: NCT02888132.


Subject(s)
Cardiomyopathy, Hypertrophic , Adult , Female , Humans , Male , Middle Aged , Cardiomyopathy, Hypertrophic/physiopathology , Cardiomyopathy, Hypertrophic/surgery , Cardiomyopathy, Hypertrophic/diagnostic imaging , Catheter Ablation/methods , Electrocardiography , Follow-Up Studies , Heart Septum/surgery , Heart Septum/diagnostic imaging , Magnetic Resonance Imaging, Cine/methods , Radiofrequency Ablation/methods , Time Factors , Treatment Outcome , Ventricular Function, Left/physiology
4.
Front Cardiovasc Med ; 10: 1261172, 2023.
Article in English | MEDLINE | ID: mdl-38162137

ABSTRACT

Background: Pompe disease (PD) is a rare, progressive, and autosomal recessive lysosomal storage disorder caused by mutations in the acid α-glucosidase gene. The clinical course and molecular mechanism of this disease in China have not been well defined. Methods: In this single-center cohort study, we investigated a total of 15 Chinese patients with Pompe disease to better understand the clinical manifestations, echocardiographic imaging and genetic characteristics in this population. Results: The median age of 15 patients at symptom onset was 5.07 months (1-24 months). The median age at diagnosis was 19.53 months (range: 3 to 109 months, n = 15). Average diagnostic delay was 13.46 months. None of the patients had received enzyme replacement therapy (ERT). Fifteen patients died at a median age of 24.80 months due to cardiorespiratory failure (range 3-120 months). Myasthenia symptoms and severe hypertrophic cardiomyopathy were universally present (15/15 = 100%). Global longitudinal strain (GLS) by echocardiography was significantly lower in these patients. After adjusting for gender, body surface area (BSA), left ventricular ejection fraction (LVEF), E/e'ratio, maximum left ventricular wall thickness (MLVWT), left ventricular posterior wall (LVPW), left ventricular outflow tract (LVOT)gradient, GLS was independently correlated with survival time (hazard ratio (HR) = 0.702, 95% confidence Interval (CI): 0.532-0.925, P = 0.012). In our cohort, we identified 4 novel GAA mutation: c.2102T > C (p.L701P), c.2006C > T (p.P669l), c.766T > A (p.Y256N), c.2405G > T (p.G802V). 12 patients were compound heterozygotes, and 4 homozygotes. Conclusions: Our study provides a comprehensive examination of PD clinical course and mutations of the GAA gene for patients in China. We showed clinical utility of echocardiography in quantifying heart involvement in patients with suspected PD. GLS can provide prognostic information for mortality prediction. We reported four novel mutations in the GAA gene for the first time. Our findings may improve early recognition of PD characteristics in Chinese patients.

5.
Front Cardiovasc Med ; 9: 1028763, 2022.
Article in English | MEDLINE | ID: mdl-36440055

ABSTRACT

Objectives: This study sought to evaluate the clinical applicability of the Liwen Liu RF™ ablation system for percutaneous intramyocardial septal radiofrequency ablation (PIMSRA). Background: Data on new cardiac radiofrequency ablation devices for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) are limited. Materials and methods: From July 2019 to July 2020, a total of 68 patients with drug-resistant HOCM, who underwent PIMSRA with the Liwen RF™ ablation system, which has an ablation electrode of stepless adjustable length, were prospectively enrolled. Safety endpoints included, amongst others, the occurrence of pericardial effusion and/or hemorrhage, cardiac arrhythmias, device failure and procedural death. The reduction in left ventricular outflow tract (LVOT) gradients at 12 months follow-up were used as a surrogate marker for device efficacy. Results: All procedures were technically successful. The total energy output time of the system was 75.8 (IQR: 30.0) min, and the average power was 43.61 ± 13.34 watts. No ablation system error occurred. The incidence of pericardial effusion or hemorrhage, transient arrhythmia and resuscitation was 8.8, 39.7, and 1.5% during procedure, respectively. None of the patients died. During 30-day follow-up, there were no complications with the exception of a pericardial effusion in one patient (1.5%). No further complications were reported after 30 days. The patients' resting [baseline: 75 (IQR: 48) vs. 12-months: 12 (IQR: 19) mmHg, p < 0.001] and provoked [baseline: 122 (IQR: 53) vs. 12-months: 41 (IQR: 59) mmHg, p < 0.001] LVOT gradients decreased significantly during follow-up. Conclusion: In this study, we demonstrate the safety and feasibility of the Liwen RF™ ablation system to treat HOCM. The system allows for significant and sustainable LVOT gradient reduction during 12-months of follow-up. Hence, the Liwen RF™ ablation system is a promising new device that has the potential to become an alternative to existing septal reduction concepts in HOCM patients.

6.
Front Immunol ; 13: 973760, 2022.
Article in English | MEDLINE | ID: mdl-36341382

ABSTRACT

Background: Emerging evidence revealed that gut microbial dysbiosis is implicated in the development of plasma cell dyscrasias and amyloid deposition diseases, but no data are available on the relationship between gut microbiota and immunoglobulin light chain (AL) amyloidosis. Methods: To characterize the gut microbiota in patients with AL amyloidosis, we collected fecal samples from patients with AL amyloidosis (n=27) and age-, gender-, and BMI-matched healthy controls (n=27), and conducted 16S rRNA MiSeq sequencing and amplicon sequence variants (ASV)-based analysis. Results: There were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of Actinobacteriota and Verrucomicrobiota was significantly higher, while Bacteroidota reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including Bifidobacterium, Akkermansia, and Streptococcus were enriched, while only 4 genera including Faecalibacterium, Tyzzerella, Pseudomonas, and Anaerostignum decreased evidently in patients with AL amyloidosis. Notably, 5 optimal ASV-based microbial markers were identified as the diagnostic model of AL amyloidosis and the AUC value of the train set and the test set was 0.8549 (95% CI 0.7310-0.9789) and 0.8025 (95% CI 0.5771-1), respectively. With a median follow-up of 19.0 months, further subgroup analysis also demonstrated some key gut microbial markers were related to disease severity, treatment response, and even prognosis of patients with AL amyloidosis. Conclusions: For the first time, we demonstrated the alterations of gut microbiota in AL amyloidosis and successfully established and validated the microbial-based diagnostic model, which boosted more studies about microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis in the future.


Subject(s)
Gastrointestinal Microbiome , Immunoglobulin Light-chain Amyloidosis , Humans , Gastrointestinal Microbiome/physiology , RNA, Ribosomal, 16S/genetics , Dysbiosis/microbiology , Feces/microbiology , Biomarkers
7.
Heart Vessels ; 36(10): 1525-1535, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33830315

ABSTRACT

The mutation MYBPC3-E334K is a culprit mutation of hypertrophic cardiomyopathy (HCM). The pathogenicity of MYBPC3-E334K is conflicting in ClinVar because of the limited segregation data and the relatively high frequency in gnomAD (0.03% overall, with 0.3% in East Asians and 0.8% in Japanese). The main aim is to clarify the clinical importance and phenotype-genotype correlations in subjects with or without MYBPC3-E334K alone. The prevalence of MYBPC3-E334K was sequenced in 1017 HCM unrelated probands. The clinical features, morphology phenotypes, and electrical phenotypes were further analyzed according to the phenotype and genotype status in families with single-mutation MYBPC3-E334K. Nine of 1017 (0.88%) unrelated HCM probands were detected harboring MYBPC3-E334K, and three of them harbored a second variant in sarcomere protein gene. Family study and co-segregation analyses indicated that patients with single-mutation MYBPC3-E334K showed autosomal dominant mode of inheritance with incomplete penetrance. The overall disease penetrance was 52.6%, and the disease penetrance was higher in males than in females (100% in men vs 25% in women, p = 0.003). The mean age at diagnosis of males was approximately 25 years younger than females (36.57 ± 18.65 vs 62.33 ± 12.10, p = 0.062). The variant MYBPC3-E334K was classified as a likely pathogenic variant, and a second sarcomere variant did not reveal obvious cumulative effects. The patients harboring single-mutation MYBPC3-E334K had incomplete penetrance, and males demonstrated higher penetrance and early onset HCM than females. A second sarcomere variant did not reveal obvious cumulative effects.


Subject(s)
Cardiomyopathy, Hypertrophic , Carrier Proteins/genetics , Adolescent , Adult , Aged , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/genetics , Female , Genotype , Humans , Male , Middle Aged , Mutation , Phenotype , Young Adult
8.
Exp Ther Med ; 21(4): 395, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33680117

ABSTRACT

Danon disease is an X-linked glycogen storage disease characterized by skeletal myopathy, cardiomyopathy and intellectual impairment. It is caused by a loss-of-function mutation in the lysosome-associated membrane protein-2 (LAMP2) gene. In the present study, exon and boarding intron analysis of 96 cardio disease-associated genes was performed in 770 patients with hypertrophic cardiomyopathy (HCM) using second-generation sequencing. Next, the identified mutations were confirmed in family members of the patients and 300 healthy controls. Detailed clinical, electrocardiographic (ECG) and echocardiographic findings were recorded. A pathogenic mutation in LAMP2 was identified in 7 patients who phenotypically presented with HCM. A total of four patients had a fragmented QRS complex (fQRS) on surface ECG. In addition, two patients presented with ventricular preexcitation with a short PR interval. Compared with the patients with protein kinase AMP-activated non-catalytic subunit γ2 syndrome and Fabry disease, the 7 patients with Danon disease presented at an earlier age, had a smaller left atrial size, a thinner maximal left ventricular wall thickness and a lower probability of pacemaker implantation. Compared with 12 sex- and age-matched patients with sarcomere-protein mutations, the 4 patients with Danon disease had a lower left ventricular outflow tract gradient and worse diastolic function. The present study provided a comprehensive comparison of different pathologies presenting with HCM and reported on features of early-onset Danon disease, including the characteristic preexcitation and fQRS on ECG. This may provide valuable information that may be utilized for the early diagnosis and treatment of patients with Danon disease. The present study was registered as a clinical trial with ClinicalTrials.gov (Sep. 2, 2016; registry no. NCT02888132).

9.
BMC Cardiovasc Disord ; 21(1): 43, 2021 01 21.
Article in English | MEDLINE | ID: mdl-33478398

ABSTRACT

BACKGROUND: Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis with poor prognosis. Currently, the predictors of cardiac involvement and prognostic staging systems are primarily based on conventional echocardiography and serological biomarkers. We used three-dimensional speckle tracking echocardiography (STE-3D) measurements of strain, hypothesizing that it could detect cardiac involvement and aid in prediction of mortality. METHODS: We retrospectively analysed 74 consecutive patients with biopsy-proven AL amyloidosis. Among them, 42 showed possible cardiac involvement and 32 without cardiac involvement. LV global longitudinal strain (GLS), global radial strain, global circumferential strain and global area strain (GAS) measurements were obtained. RESULTS: The GLS and GAS were considered significant predictors of cardiac involvement. The cut-off values discriminating cardiac involvement were 16.10% for GLS, 32.95% for GAS. During the median follow-up of 12.5 months (interquartile range 4-25 months), 20 (27%) patients died. For the Cox proportional model survival analysis, heart rate, cardiac troponin T, NT-proBNP levels, E/e', GLS, and GAS were univariate predictors of death. Multivariate Cox model showed that GLS ≤ 14.78% and cardiac troponin T ≥ 0.049 mg/l levels were independent predictors of survival. CONCLUSIONS: STE-3D measurements of LV myocardial mechanics could detect cardiac involvement in patients with AL amyloidosis; GLS and cardiac biomarkers can provided prognostic information for mortality prediction.


Subject(s)
Cardiomyopathies/diagnostic imaging , Echocardiography, Three-Dimensional , Immunoglobulin Light-chain Amyloidosis/diagnostic imaging , Myocardial Contraction , Ventricular Function, Left , Aged , Biomarkers/blood , Cardiomyopathies/blood , Cardiomyopathies/mortality , Cardiomyopathies/physiopathology , Disease Progression , Female , Humans , Immunoglobulin Light-chain Amyloidosis/blood , Immunoglobulin Light-chain Amyloidosis/mortality , Immunoglobulin Light-chain Amyloidosis/physiopathology , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Troponin T/blood
10.
J Electrocardiol ; 61: 164-169, 2020.
Article in English | MEDLINE | ID: mdl-32721657

ABSTRACT

OBJECTIVES: This study aimed to determine whether the serial changes of the electrocardiogram is associated with regression of left ventricular hypertrophy (LVH) after Liwen procedure. BACKGROUND: Clinical application of the echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) is an innovative approach to treat hypertrophic obstructive cardiomyopathy (HOCM). METHODS: We enrolled 30 consecutive patients with HOCM who had undergone Liwen procedure in our Hypertrophic Cardiomyopathy Center, from June 2016 to January 2018. Electrocardiography (ECG) and echocardiogram were performed before and after Liwen procedure, and at each follow-up (1-week, 1, 3, 6 months and 1 year). The Sokolow-Lyon index (SLi), Q wave, R wave, S wave amplitude of 12-lead ECG and interventricular septal (IVS) thickness, left ventricular mass index (LVMI) by echocardiograms were measured in each patient. The sum of the ECG QRS amplitude on each lead was calculated. The reduction of SLi and QRS amplitude were used as improvement index. RESULTS: The ECG leads with most improvement rate of the QRS wave amplitude of all cases were V1 and V2, both at 90%. The QRS wave amplitude in V1 leads and SLi were positively correlated with IVS thickness and LVMI at baseline and 1 year after Liwen procedure, respectively. The reduction of IVS thickness, LVMI and QRS wave amplitude in leads V1 and V2 were significant at one month after ablation and the follow-up period. SLi was significantly decreased at 3 months during the observation period. Similarly, the improvement of ECG QRS wave amplitude after the Liwen procedure tracked the gradual thinning of the IVS and the changes of SLi reflected the regression of LVH. CONCLUSION: The QRS wave amplitude reductions in lead V1 and SLi may be good indicators for evaluating the postoperative interventricular septal remodeling of the Liwen procedure.


Subject(s)
Cardiomyopathy, Hypertrophic , Radiofrequency Ablation , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/surgery , Echocardiography , Electrocardiography , Follow-Up Studies , Humans
11.
Int J Nanomedicine ; 15: 1321-1333, 2020.
Article in English | MEDLINE | ID: mdl-32161461

ABSTRACT

INTRODUCTION: Currently, the unsatisfactory treatment of cardiac hypertrophy is due to the unbridled myocardial fibrosis. Melatonin has been demonstrated to ameliorate cardiac hypertrophy and its accompanied fibrosis in previous studies. But it is not clinically appealing due to its short-lasting time against the hostile microenvironment when administered orally. METHODS: Herein, to address this, poly (lactide) polycarboxybetaine (PLGA-COOH) accompanied by cardiac homing peptide (CHP) and superparamagnetic iron oxide nanoparticles (SPIONs) were used to establish a novel drug delivery and transportation strategy for melatonin via a facile two-step emulsion method. This study characterized these nanoparticles (CHP-mel@SPIONs) and tested their delivery to the hypertrophied heart and their effect on myocardial hypertrophy and fibrosis in an animal model of pressure overload-induced cardiac hypertrophy. RESULTS: The engineered magnetic nanoparticles of CHP-mel@SPIONs were spherical (diameter = 221 ± 13 nm) and had a negative zeta potential of -19.18 ± 3.27 mV. The CHP-mel@SPIONs displayed excellent drug encapsulation capacities of SPIONs (75.27 ± 3.1%) and melatonin (77.69 ± 6.04%) separately, and their magnetic properties were characterized by constructing magnetic hysteresis curves and exhibited no remnant magnetization or coercivity. The animal experiments showed that compared with mel@SPIONs, CHP-mel@SPIONs accumulated more in the heart, especially in the presence of an external magnetic field, with in vivo echocardiography and RT-PCR and histological assessments confirming the amelioration of the myocardial hypertrophy and fibrosis with low drug doses. CONCLUSION: This simple biocompatible dual-targeting nanoagent may be a potential candidate for the guided clinical therapy of heart disease.


Subject(s)
Cardiomegaly/drug therapy , Drug Delivery Systems/methods , Magnetite Nanoparticles/chemistry , Melatonin/administration & dosage , Myocardium/pathology , Animals , Cardiomegaly/pathology , Disease Models, Animal , Ferrosoferric Oxide/chemistry , Fibrosis , Heart/drug effects , Magnetic Fields , Melatonin/pharmacology , Nanostructures , Peptides/chemistry , Pressure , Rats, Sprague-Dawley
12.
Cardiology ; 145(4): 227-235, 2020.
Article in English | MEDLINE | ID: mdl-32097929

ABSTRACT

OBJECTIVES: This study aimed to assess left ventricular (LV) energy loss (EL), circulation and vortex area using vector flow mapping (VFM) in patients with latent obstructive hyper-trophic cardiomyopathy (LOHCM) and nonobstructive hypertrophic cardiomyopathy (NOHCM). METHODS: Fourteen LOHCM patients, 10 NOHCM patients, and 11 healthy individuals were evaluated by transthoracic echocardiography. An offline VFM workstation was used to analyze the LV blood flow patterns and fluid dynamics. The hemodynamic parameters, EL, circulation, and vortex area in 7 cardiac phases were calculated and analyzed. RESULTS: Compared with controls and NOHCM patients, EL was significantly higher in -LOHCM patients during the rapid ejection phase, slow ejection (SE) phase, and isovolumetric relaxation phase (p < 0.05). LOHCM patients also showed increased circulation during SE compared to the other two groups (p < 0.05). The ability to discriminate between NOHCM and LOHCM was assessed by the area under the receiver-operating characteristic curve (AUC), and EL during SE was found to have the largest AUC (0.964); the best cutoff value was 6.34 J/m3/s, with a sensitivity of 100% and specificity of 80%. CONCLUSIONS: The VFM technique can detect abnormal changes of LV EL and vortex characteristics in hypertrophic cardiomyopathy patients. Compared with controls and NOHCM patients, the LOHCM patients have worse systolic and diastolic functions.


Subject(s)
Cardiomyopathy, Hypertrophic , Heart Ventricles , Blood Flow Velocity , Cardiomyopathy, Hypertrophic/diagnostic imaging , Echocardiography , Heart Ventricles/diagnostic imaging , Humans , Systole
13.
Cardiol Young ; 28(9): 1106-1114, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29978770

ABSTRACT

BACKGROUND: We previously reported four heterozygous missense mutations of MYH7, KCNQ1, MYLK2, and TMEM70 in a single three-generation Chinese family with dual Long QT and hypertrophic cardiomyopathy phenotypes for the first time. However, the clinical course among the family members was various, and the potential myocardial dysfunction has not been investigated. OBJECTIVES: The objective of this study was to investigate the echocardiographic and electrocardiographic characteristics in a genetic positive Chinese family with hypertrophic cardiomyopathy and further to explore the association between myocardial dysfunction and electric activity, and the identified mutations. METHODS: A comprehensive echocardiogram - standard two-dimensional Doppler echocardiography and three-dimensional speckle tracking echocardiography - and electrocardiogram were obtained for members in this family. RESULTS: As previously reported, four missense mutations - MYH7-H1717Q, KCNQ1-R190W, MYLK2-K324E, and TMEM70-I147T - were identified in this family. The MYH7-H1717Q mutation carriers had significantly increased left ventricular mass indices, elevated E/e' ratio, deteriorated global longitudinal stain, but enhanced global circumferential and radial strain compared with those in non-mutation patients (all p<0.05). The KCNQ1-R190W carriers showed significantly prolonged QTc intervals, and the MYLK2-K324E mutation carriers showed inverted T-waves (both p<0.05). However, the TMEM70-I147T mutation carriers had similar echocardiography and electrocardiographic data as non-mutation patients. CONCLUSIONS: Three of the identified four mutations had potential pathogenic effects in this family: MYH7-H1717Q was associated with increased left ventricular thickness, elevated left ventricular filling pressure, and altered myocardial deformation; KCNQ1-R190W and MYLK2-K324E mutations were correlated with electrocardiographic abnormalities reflected in long QT phenotype and inverted T-waves, respectively.


Subject(s)
Cardiomyopathy, Hypertrophic, Familial/diagnosis , Echocardiography, Doppler/methods , Echocardiography, Three-Dimensional/methods , Genetic Predisposition to Disease , Heart Ventricles/physiopathology , Myocardial Contraction/physiology , Stroke Volume/physiology , Adolescent , Adult , Aged , Cardiac Myosins/genetics , Cardiac Myosins/metabolism , Cardiomyopathy, Hypertrophic, Familial/genetics , Cardiomyopathy, Hypertrophic, Familial/physiopathology , Child , China/epidemiology , Electrocardiography , Female , Heart Ventricles/diagnostic imaging , Humans , Male , Middle Aged , Morbidity/trends , Mutation, Missense , Pedigree , Phenotype , Young Adult
14.
Europace ; 18(4): 602-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-25825456

ABSTRACT

AIMS: Hypertrophic cardiomyopathy (HCM) mainly results from autosomal-dominant inherited single heterozygous mutations in cardiac sarcomere genes. Contributions of multiple gene mutations to disease heterogeneity in a three-generation family were investigated. METHODS: Clinical, electrocardiographic (ECG), and echocardiographic examination in members of a three-generation Chinese family was followed by exon and boarding intron analysis of 96 genes in the proband using second-generation sequencing. The identified mutations were confirmed by bi-directional Sanger sequencing in all family members and 300 healthy controls. RESULTS: Four missense mutations were detected in the family. These were two novel MYH7-H1717Q and MYLK2-K324E mutations accompanied by the KCNQ1-R190W and TMEM70-I147T mutations. The proband carried all four mutations and showed overlapping HCM and LQT1 phenotypes. Five family members each carried two mutations. Subject II-2 only carried TMEM70-I147T. MYH7-H1717Q and TMEM70-I147T came from the paternal side, whereas KCNQ1-R190W and MYLK2-K324E came from the maternal side. Left ventricle mass indices in MYH7-H1717Q carriers were significantly higher than in non-H1717Q carriers (90.05 ± 7.33 g/m(2), 63.20 ± 4.53 g/m(2), respectively, P < 0.01). Four KCNQ1-R190W carriers showed QTc intervals that were significantly more prolonged than those in non-R190W carriers (472.25 ± 16.18 and 408.50 ± 7.66 ms, respectively, P < 0.05). All MYLK2-K324E carriers showed inverted ECG T waves. The subject with only a TMEM70-I147T mutation showed normal ECG and echocardiographs, suggesting that this had less pathological effects at least in this family. CONCLUSIONS: We demonstrate dual LQT1 and HCM phenotypes in this multiple LQT1- and HCM-related gene mutation carrier family for the first time and suggest that LQT-related gene mutations associate with QT interval prolongation and/or arrhythmia in HCM patients.


Subject(s)
Cardiac Myosins/genetics , Cardiomyopathy, Hypertrophic, Familial/genetics , Heterozygote , KCNQ1 Potassium Channel/genetics , Membrane Proteins/genetics , Mitochondrial Proteins/genetics , Mutation, Missense , Myosin Heavy Chains/genetics , Myosin-Light-Chain Kinase/genetics , Romano-Ward Syndrome/genetics , Adult , Aged , Asian People/genetics , Cardiomyopathy, Hypertrophic, Familial/diagnosis , Cardiomyopathy, Hypertrophic, Familial/ethnology , Cardiomyopathy, Hypertrophic, Familial/physiopathology , Case-Control Studies , Child , China , DNA Mutational Analysis , Echocardiography , Electrocardiography , Female , Genetic Association Studies , Genetic Markers , Genetic Predisposition to Disease , Heredity , Humans , Male , Middle Aged , Pedigree , Phenotype , Romano-Ward Syndrome/diagnosis , Romano-Ward Syndrome/ethnology , Romano-Ward Syndrome/physiopathology , Young Adult
15.
Phys Rev Lett ; 110(13): 135501, 2013 Mar 29.
Article in English | MEDLINE | ID: mdl-23581334

ABSTRACT

The irreversible damage at cracks during the fatigue of crystalline solids is well known. Here we report on in situ high-energy x-ray evidence of reversible fatigue behavior in a nanocrystalline NiFe alloy both in the plastic zone and around the crack tip. In the plastic zone, the deformation is fully recoverable as the crack propagates, and the plastic deformation invokes reversible interactions of dislocation and twinning in the nanograins. But around the crack tip lies a regime with reversible grain lattice reorientation promoted by a change of local stress state. These observations suggest unprecedented fatigue deformation mechanisms in nanostructured systems that are not addressed theoretically.

16.
Angew Chem Int Ed Engl ; 50(14): 3158-63, 2011 Mar 28.
Article in English | MEDLINE | ID: mdl-21374772
18.
Microsc Microanal ; 16(2): 183-93, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20187990

ABSTRACT

We evaluate the probe forming capability of a JEOL 2200FS transmission electron microscope equipped with a spherical aberration (Cs) probe corrector. The achievement of a real space sub-Angstrom (0.1 nm) probe for scanning transmission electron microscopy (STEM) imaging is demonstrated by acquisition and modeling of high-angle annular dark-field STEM images. We show that by optimizing the illumination system, large probe currents and large collection angles for electron energy loss spectroscopy (EELS) can be combined to yield EELS fine structure data spatially resolved to the atomic scale. We demonstrate the probe forming flexibility provided by the additional lenses in the probe corrector in several ways, including the formation of nanometer-sized parallel beams for nanoarea electron diffraction, and the formation of focused probes for convergent beam electron diffraction with a range of convergence angles. The different probes that can be formed using the probe corrected STEM opens up new applications for electron microscopy and diffraction.

20.
Langmuir ; 24(20): 11928-34, 2008 Oct 21.
Article in English | MEDLINE | ID: mdl-18788821

ABSTRACT

Simple galvanic reactions between highly doped n-type GaAs wafers and a pure aqueous solution of AgNO 3 at room temperature provide an easy and efficient protocol to directly deposit uniform Ag nanoplates with tunable dimensions on the GaAs substrates. The anisotropic growth of the Ag nanoplates in the absence of surfactant molecules might be partially ascribed to the codeposition of oxides of gallium and arsenic, which are revealed by extensive data from electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy, during the growth of the Ag nanoplates. The electron microscopic characterization shows that each Ag nanoplate has a "necked" geometry, that is, it pins on the GaAs lattices through only a tiny neck (with sizes of <10 nm). In addition, the as-grown Ag nanoplates exhibit strong enhancement toward Raman scattering of materials on (or around) their surfaces.

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