Liwen Liu

Dual LQT1 and HCM phenotypes associated with tetrad heterozygous mutations in KCNQ1, MYH7, MYLK2, and TMEM70 genes in a three-generation Chinese family

AIMSnHypertrophic 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.nnnMETHODSnClinical, 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.nnnRESULTSnFour 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.nnnCONCLUSIONSnWe 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.

Reduction of left ventricular longitudinal global and segmental systolic functions in patients with hypertrophic cardiomyopathy: Study of two-dimensional tissue motion annular displacement

The early detection of abnormal left ventricular systolic functions in patients with hypertrophic cardiomyopathy (HCM) remains a challenge. The aim of this study was to identify a novel method for the assessment of left ventricular systolic function in patients with HCM. A total of 65 patients with HCM were included in this study. The patients were divided into obstructive HCM (HOCM; 16 cases) and non-obstructive HCM (NOHCM; 49 cases) groups. The healthy control group comprised 48 participants. Two-dimensional (2D) speckle-tracking technology was used to measure the left ventricular global and segmental longitudinal strains and mitral annular displacement (MADs). Compared with healthy control group, the six segmental strains and the global strain of the left ventricle (LSglobal) increased while six segmental MADs and MADglobal of the mitral annulus decreased in the HOCM and NOHCM groups (P<0.05). In addition, the six segmental MADs of the mitral annulus were significantly negatively correlated with the six segmental strains of the left ventricle (r=−0.744 to −0.647, P<0.001). MADglobal was significantly negatively correlated with LSglobal (r=−0.857, P<0.001). The tissue motion annular displacement (TMAD) at the midpoint was significantly negatively correlated with LSglobal (r=−0.871, P<0.001). The 2D TMAD technique of measuring MAD was feasible and practically approachable for rapidly evaluating the left ventricular longitudinal global and segmental systolic functions of patients with HCM.

The Cumulative Effects of the MYH7 -V878A and CACNA1C -A1594V Mutations in a Chinese Family with Hypertrophic Cardiomyopathy

Aims: We investigated the pathogenesis of MYH7-V878A and CACNA1C-A1594V mutations in a Chinese family with hypertrophic cardiomyopathy. Methods: Clinical, electrocardiographic (ECG), echocardiographic, and cardiac magnetic resonance (CMR) examinations of members of a Chinese family were followed by exon and boarding intron analyses of 96 genes in the proband using second-generation sequencing. We confirmed the mutations by bidirectional Sanger sequencing in the members and in 300 healthy controls. Results: We detected MYH7-V878A and CACNA1C-A1594V mutations in this family. The members with both mutations showed inverted T-waves and ST-segment depression in ECG recordings, severe left ventricular (LV) hypertrophy in echocardiography, and myocardial fibrosis in CMR; subject II-11 did not show late gadolinium enhancement. Among those with only the MYH7-V878A mutation, subject III-7 showed abnormal ECG recordings, asymmetric septal hypertrophy, and myocardial fibrosis, and subjects II-13 and III-15 showed some abnormal repolarization, borderline LV wall thickness, and normal CMR findings. Those with only the CACNA1C-A1594V mutation showed nearly normal readings in all examinations. The members with both mutations displayed more severe LV hypertrophy and elevated LV filling pressure than those with 1 or no mutation (p < 0.05). Conclusion: Our results suggest that the pathogenesis of MYH7-V878A and CACNA1C-A1594V mutations may have a cumulative effect.

Echocardiography-guided percutaneous per-ventricular laser ablation of ventricular septum: in vivo study in a canine model

Surgical myectomy and ethanol ablation are established intervention strategies for left ventricular outflow obstruction in hypertrophic cardiomyopathy. Safety and efficacy limitations of these interventions call for a minimally invasive, potentially safer, and more efficacious strategy. In this study, we aimed to evaluate the feasibility of echocardiography-guided percutaneous per-ventricular laser ablation of a ventricular septum in a canine model. Six domestic dogs were chosen for the study. A 21G needle was inserted into the right ventricle with its tip reaching the targeted basal to mid-septum, after which laser ablation was performed as follows: 1-W laser for 3xa0min (180xa0J) at the basal segment and 5xa0min (300xa0J) at middle segment of the septum, respectively. Echocardiography, blood chemistry tests, and pathology examination were performed to assess the results of laser ablation. No death or major complications, i.e., tamponade, pericardial effusion, or ventricular fibrillation, occurred. The laser-ablated areas were well demarcated in the results of the pathological examination. The diameters of the ablated regions were 4.42u2009±u20090.57 and 5.28u2009±u20090.83xa0mm for 3 and 5xa0min ablation, respectively. Pre-ablation and post-ablation, cardiac enzymes were found to increase significantly while no significant differences were found among M-mode, 2D (LVEF), pulsed-wave (PW) Doppler, and tissue Doppler imaging (TDI) measurements. Contrast echocardiography confirmed the perfusion defects in the ablated regions. Microscopically, the ablated myocardium showed coagulative changes and a sparse distribution of disappearing nuclei and an increase in eosinophil number were observed. Our study suggests that percutaneous and per-ventricular laser ablation of the septum is feasible, potentially safe and efficacious, and warrants further investigation and validation.

A preliminary clinical study on high-intensity focused ultrasound therapy for tubal pregnancy

Our aim was to explore the clinical application value of high-intensity focused ultrasound (HIFU) therapy for tubal pregnancy. Forty hospitalized patients with tubal pregnancies (28 cases of non-ruptured tubal pregnancy and 12 cases of ruptured tubal pregnancy) were selected to receive HIFU therapy. Serum human chorionic gonadotropin (β-HCG) concentrations were compared before and after treatment. Serum β-HCG was measured weekly and patients received observation only if the concentration decreased by 15% or more, compared with the previous value. Patients were given supplement HIFU therapy if the decrease in the serum β-HCG was <15% within two weeks. Ultrasound was used to detect the volume changes in the ectopic lesions before and after treatment, and changes in vital signs and complications were recorded. Contrast-enhanced ultrasonography was used to assess fallopian tube patency after treatment. HIFU treatment was successful in 33 of the 40 patients (82%). Seven patients failed HIFU treatment and received surgical therapy (18%). Before and after treatment, serum β-HCG concentrations and lesion volume were significantly different (P < 0.05, P < 0.01, respectively). Post-treatment tubal contrast-enhanced ultrasonography showed tubal patency on the affected side in 21 cases (64%) at six months and in 27 cases (82%) at 12 months. In conclusion, HIFU is safe and effective, and can be a treatment option for tubal pregnancy.

Percutaneous trans-apex intra-septal radiofrequency ablation of hypertrophic cardiomyopathy

Abstract A 70-year-old woman presented with severe hypertrophic obstructive cardiomyopathy (HOCM) (maximum ventricular septum thickness of 28u2009mm, peak pressure gradient (PG) in the left ventricular outflow tract (LVOT) of 153u2009mmHg). We performed percutaneous trans-apex intra-septal radiofrequency ablation (PTAISRA) of the interventricular septum under guidance of transthoracic echocardiography. At six-months follow up, the symptoms were significantly relieved; the septal thickness was reduced to 18u2009mm and the peak LVOT PG reduced to 44u2009mmHg. This case highlights a novel use of radiofrequency ablation for the treatment of HOCM. Long-term safety and efficacy merit evaluation.

Percutaneous Intramyocardial Septal Radiofrequency Ablation for Hypertrophic Obstructive Cardiomyopathy

BACKGROUNDnIn patients with disabling symptoms caused by hypertrophic obstructive cardiomyopathy (HOCM), echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) could be a less invasive treatment option.nnnOBJECTIVESnThis study aimed to investigate the safety and efficacy of the PIMSRA for left ventricular outflow tract (LVOT) gradient reduction in HOCM.nnnMETHODSnThe study enrolled 15 patients with HOCM. These patients underwent electrocardiography, imaging, and blood biochemistry examination over 6xa0months of follow-up.nnnRESULTSnAt 6xa0months of follow-up, patients showed significant reductions in peak LVOT gradients (resting gradient: from 88.00 [66.00]xa0mmxa0Hg to 11.00 [6.00]xa0mmxa0Hg; pxa0=xa00.001; stress-induced gradient: from 117.00 [81.00]xa0mmxa0Hg to 25.00xa0[20.00]xa0mmxa0Hg; pxa0=xa00.005) and interventricular septum (IVS) thickness (anterior IVS: from 25.00 [21.00]xa0mm to 14.00 [12.00]xa0mm; pxa0=xa00.001; posterior IVS: from 24.00 [21.00]xa0mm to 14.00 [11.50]xa0mm; pxa0=xa00.001). The reductions in IVS thickness and LVOT gradients were associated with improvement in New York Heart Association functional classification (from 3.00 [2.00] to 1.00 [1.00]; pxa0< 0.001), total exercise time (from 6.00 [5.50]xa0min to 9.00 [8.00] min; pxa0=xa00.007), and pro B-type natriuretic peptide levels (from 924.00 [370.45] pg/ml to 137.45 [75.73] pg/ml; pxa0=xa00.028). No patient had bundle branch block or complete heart block.nnnCONCLUSIONSnPIMSRA is a safe and effective treatment approach for severe, symptomatic HOCM and results in sustained improvement in exercise capacity, persistent reduction in LVOT gradient, and sustained improvement in cardiacxa0function.

Cardiomyocyte-targeted and 17β-estradiol-loaded acoustic nanoprobes as a theranostic platform for cardiac hypertrophy

BackgroundTheranostic perfluorocarbon nanoprobes have recently attracted attention due to their fascinating versatility in integrating diagnostics and therapeutics into a single system. Furthermore, although 17β-estradiol (E2) is a potential anti-hypertrophic drug, it has severe non-specific adverse effects in various organs. Therefore, we have developed cardiomyocyte-targeted theranostic nanoprobes to achieve concurrent targeted imaging and treatment of cardiac hypertrophy.ResultsWe had successfully synthesized E2-loaded, primary cardiomyocyte (PCM) specific peptide-conjugated nanoprobes with perfluorocarbon (PFP) as a core (PCM-E2/PFPs) and demonstrated their stability and homogeneity. In vitro and in vivo studies confirmed that when exposed to low-intensity focused ultrasound (LIFU), these versatile PCM-E2/PFPs can be used as an amplifiable imaging contrast agent. Furthermore, the significantly accelerated release of E2 enhanced the therapeutic efficacy of the drug and prevented systemic side effects. PCM-E2/PFPsu2009+u2009LIFU treatment also significantly increased cardiac targeting and circulation time. Further therapeutic evaluations showed that PCM-E2/PFPsu2009+u2009LIFU suppressed cardiac hypertrophy to a greater extent compared to other treatments, revealing high efficiency in cardiac-targeted delivery and effective cardioprotection.ConclusionOur novel theranostic nanoplatform could serve as a potential theranostic vector for cardiac diseases.

Echocardiography Guided Liwen Procedure™ for the treatment of obstructive hypertrophic cardiomyopathy in a patient with prior aortic valve replacement surgery: Liwen procedure for intra-myocardial radiofrequency ablation

We successfully treated a patient who was diagnosed of having hypertrophic obstructive cardiomyopathy after the aortic valve replacement surgery for the concomitant aortic stenosis. We report this first in kind new procedure exclusively developed in our center, Liwen procedureTM (percutaneous intramyocardial septal radiofrequency ablation), for patients with left ventricular outflow tract obstruction in spite of maximal medical therapy. The procedure was performed under transthoracic echo guidance. We discussed the technical details, safety, and effectiveness with corresponding images. The patient did well one year after the procedure without LVOT obstruction or arrhythmia.

GW28-e0050 Assessment 2D and 3D global longitudinal Strain of abnormal LV myocardial deformation properties Using 3D Speckle-Tracking Echocardiography in young HCM

Hypertrophic cardiomyopathy (HCM) is a disease predisposes to unexplained left ventricular (LV) hypertrophy and dysfunction and non-dilated ventricular chambers associated unusual myocardial mechanics. The most serious complications of HCM is sudden death for young subclinical patients, thus,