Prognostic predictive value of TLR4 polymorphisms in Han Chinese population with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease and is an important cause of sudden death in patients of all ages. The aim of this study was to find out whether Toll-like receptor-4 (TLR4) polymorphism is associated with HCM. To explore the association between TLR4 gene polymorphisms and HCM, 486 HCM patients and 214 healthy controls were enrolled in a case–control study of Chinese Han population. Two single nucleotide polymorphisms (SNPs) in the promoter region of TLR4 gene, ?728G > C (rs11536865) and ?2081G > A (rs10983755), were genotyped by PCR restriction fragment length polymorphism (PCR-RFLP). The associations between TLR4 SNPs and overall survival (OS) of HCM patients were analyzed by the Kaplan–Meier estimation method and Cox proportional hazards regression analysis. Serum TLR4 level was determined by ELISA. Our results showed that the C allelic frequency of ?728G > C and A allelic frequency of ?2081G > A were higher in HCM patients than those in controls (P < 0.001). The ratios of genotype frequencies for both SNPs were associated with HCM susceptibility under three genetic models (P < 0.01). Two SNPs were also associated with the OS in HCM patients (P < 0.001). The CC genotype of ?728G > C and AA genotype of ?2081G > A were associated with poor prognosis of HCM (P < 0.001). Moreover, HCM patients had a higher serum TLR4 level compared with the controls (242.6 pg/ml versus 135.7 pg/ml, P = 0.027). In addition, significant associations were observed between CC genotype of ?728G > C or AA genotype of ?2081G > A and plasma TLR4 level (P < 0.01). The results of this study indicated that TLR4 polymorphisms may be a genetic susceptibility factor for HCM in the Han Chinese population.     

Fragmented ECG as a Risk Marker in Cardiovascular Diseases

Various noninvasive tests for risk stratification of sudden cardiac death (SCD) were studied, mostly in the context of structural heart disease such as coronary artery disease (CAD), cardiomyopathy and heart failure but have low positive predictive value for SCD. Fragmented QRS complexes (fQRS) on a 12-lead ECG is a marker of depolarization abnormality. fQRS include presence of various morphologies of the QRS wave with or without a Q wave and includes the presence of an additional R wave (R’) or notching in the nadir of the R’ (fragmentation) in two contiguous leads, corresponding to a major coronary artery territory. fQRS represents conduction delay from inhomogeneous activation of the ventricles due to myocardial scar. It has a high predictive value for myocardial scar and mortality in patients CAD. fQRS also predicts arrhythmic events and mortality in patients with implantable cardioverter defibrillator. It also signifies poor prognosis in patients with nonischemic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and Brugada syndrome. However, fQRS is a nonspecific finding and its diagnostic prognostic should only be interpreted in the presence of pertinent clinical evidence and type of myocardial involvement (structural vs. structurally normal heart).     

Cardiac manifestations of subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is a devastating condition. It carries a high mortality rate, with 12% of patients dying before reaching the hospital. Aside from its neurological morbidities, SAH is associated with significant medical complications. Cardiac manifestations are common and can impact morbidity and mortality in SAH patients. This article will discuss the cardiac manifestations of SAH.     

Live/Real Time Three‐Dimensional Transesophageal Echocardiographic Assessment of Ventricular Septal Volume and Mass before and after Myectomy in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common genetically transmitted cardiomyopathy. In patients resistant to medical management, myectomy is the surgical procedure of choice to reduce the symptoms of left ventricular outflow obstruction. Two‐dimensional transesophageal echocardiography (2DTEE) has become part of the operative procedure by decreasing the incidence of postoperative complications. However, because of the three‐dimensional geometry of left ventricular outflow tract, it is unable to comprehensively assess the location and severity of the obstruction and to provide accurate guidance during myectomy. In this study, 10 patients with HCM underwent live/real time three‐dimensional transesophageal echocardiography (3DTEE) intra‐operatively to measure the volume of the resected septum. This volume correlated well with the volume of the resected septal muscle directly obtained using a graduating cylinder containing water (r = 0.9, P < 0.000). 3DTEE may be potentially used as an adjunct to guide the surgeon in performing an adequate myectomy with a lower incidence of residual obstruction and complications such as an iatrogenic ventricular septal defect.     

Takotsubo cardiomyopathy in acute coronary syndrome; clinical features and contribution of cardiac magnetic resonance during the acute and convalescent phase

Abstract

Objectives. Takotsubo cardiomyopathy (TTC) is a diagnostic entity that is increasingly being recognized. Data from cardiac magnetic resonance (CMR) imaging and its impact on differential diagnosis are limited. Methods and results. After 26 months, coronary angiography revealed normal coronary arteries and left ventriculography and/or echocardiography left ventricular dysfunction with apical ballooning in 20 patients with acute coronary syndrome (ACS). Four patients were excluded from CMR and in three patients an alternative diagnosis was revealed. Thirteen patients (all female; 60 ± 8 years) with TTC underwent a multisequential CMR, in which all showed myocardial oedema with an elevated T2 ratio in the apical region (2.4 ± 0.4; p < 0.001 vs. healthy controls), and five patients an elevated global relative enhancement (gRE; 3.7 ± 1.4; p < 0.05 vs. healthy controls). No late gadolinium enhancement (LGE) was detected on CMR. Follow-up after 132 ± 33 days showed a normalized left ventricular ejection fraction, myocardial mass, T2 ratio, and gRE in all patients. Conclusions. TTC is a small but definite group among patients with ACS and normal coronary arteries. CMR allows differentiating TTC from other causes such as myocarditis and cardiomyopathies, as well as to identify the transient increase of myocardial mass and resolution of myocardial oedema as the systolic dysfunction improves. Therefore, CMR might add valuable information for the differential diagnoses and therapeutic decision-making in patients with suspected TTC.     

肥厚型心肌病诊治的辅助检查进展

肥厚型心肌病是一种常染色体显性遗传性心肌疾病,其遗传特性、临床表型、病程和预后存在显著异质性,临床诊治极具挑战性.多普勒组织成像、定量组织速度成像、组织应变率成像、心脏磁共振及延迟钆增强等辅助检查对早期诊断、指导治疗及判断预后起重要作用.该文就肥厚型心肌病在辅助检查方面的进展作一综述.     

A novel recessive 15-hydroxyprostaglandin dehydrogenase mutation in a family with primary hypertrophic osteoarthropathy

Abstract

We present two PHO siblings having a novel homozygous truncating mutation in HPGD. The purpose of the study was to attempt medical treatment, and to find the HPGD mutation causing the disease, in a 22-year old Turkish male and his 23-year old sister afflicted with primary hypertrophic osteoarthropathy (PHO). In combination with NSAIDs and colchicine, treatment with sulfasalazine was started in both cases, and methotrexate was added to the treatment regimen of the female patient at the end of the first year. The patients were found to be typical PHO. Ultrasonographic examination of the joints revealed synovitis and inflammation by B mode and power Doppler ultrasonography. Joint symptoms responded to sulfasalazine treatment in both patients. However, after the addition of methotrexate, the female patient had better remission. All exons of HPGD, the known disease gene, were analyzed by Sanger sequencing. A homozygous 2-bp deletion (c.310_311delCT or p.L104AfsX3) was identified. Seven relatives carrying the mutation in the heterozygous state were examined and none was found affected. Although not specific for this disease, skin, soft tissue and joint ultrasonography can be helpful for evaluation of the musculoskeletal findings in the patients.