Successful Right Ventricular Tachycardia Ablation in a Patient with Left Ventricular Non-compaction Cardiomyopathy

We report a case of a 67-year old male with a recent diagnosis of left ventricular noncompaction (LVNC), initially presenting with symptomatic ventricular ectopy and runs of non-sustained ventricular tachycardia (VT). This ventricular arrhythmia originated in a structurally normal right ventricle (RV) and was successfully localized and ablated with the aid of the three-dimensional mapping and remote magnetic navigation.     

Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy

Objective

Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.

Methods

A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m² as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up.

Results

Patients were followed up to an average age of 15.9 ± 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027).

Conclusions

We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts.     

Right Ventricular Function Quantification in Takotsubo Cardiomyopathy Using Two-Dimensional Strain Echocardiography

Aims

This study sought to characterize global and regional right ventricular (RV) myocardial function in patients with Takotsubo cardiomyopathy (TC) using 2D strain imaging.

Methods

We compared various parameters of RV and left ventricular (LV) systolic function between 2 groups of consecutive patients with TC at initial presentation and upon follow-up. Group 1 had RV involvement and group 2 did not have RV involvement.

Results

At initial presentation, RV peak systolic longitudinal strain (RVPSS) and RV fractional area change (RVFAC) were significantly lower in group 1 (−13.2±8.6% vs. −21.8±5.4%, p = 0.001; 30.7±9.3% vs. 43.5±6.3%, p = 0.001) and improved significantly upon follow-up. Tricuspid annular plane systolic excursion (TAPSE) did not differ significantly at initial presentation between both groups (14.8±4.1 mm vs. 17.9±3.5 mm, p = 0.050). Differences in regional systolic RV strain were only observed in the mid and apical segments. LV ejection fraction (LVEF) and LV global strain were significantly lower in group 1 (36±8% vs. 46±10%, p = 0.006 and −5.5±4.8% vs. −10.2±6.2%, p = 0.040) at initial presentation. None of the parameters were significantly different between the 2 groups upon follow-up. A RVPSS cut-off value of >−19.1% had a sensitivity of 85% and a specificity of 71% to discriminate between the 2 groups.

Conclusion

In TC, RVFAC, RVPSS, LVEF and LV global strain differed significantly between patients with and without RV dysfunction, whereas TAPSE did not. 2 D strain imaging was feasible for the assessment of RV dysfunction in TC and could discriminate between patients with and without RV involvement in a clinically meaningful way.     

血流向量图评价扩张性心肌病患者左室收缩功能的研究

目的：应用血流向量图（VFM）对扩张性心肌病（DCM）患者收缩期左室心腔血液流场变化情况进行检测,初步探讨VFM技术在评价DCM患者左心室收缩功能方面的临床价值。方法：选择临床诊断为DCM患者30例作为病例组,另选30例体检健康者作为对照组。在血流向量图条件下测量两组取样线上收缩期负向总流量（SystoleQ-,SQ-）在涡流条件下测量涡流的最大流量（Qmax）、半值面积（S）、涡流半径（r）以及涡流强度（Qmax／S）,并比较两组差异。应用Simpson双平面法获取左心室射血分数（EF）,并与SQ-、Qmax／S进行相关性分析。结果：两组比较病例组基底段、中间段、心尖段收缩期负向总流量SQ-、两组组内比较基底段、中间段、心尖段收缩期负向总流量SQ．均呈逐渐递减变化趋势（P均〈0．01）。收缩期涡流最大流量Qmax及涡流强度Qmax／S测值均低于对照组（P〈0．01）;收缩期涡流半值面积S、涡流半径r均大于对照组（P〈0．01）：Qmax／S与EF呈正相关,（r=0．78,P〈0．01）;结论：VFM技术可以定量分析DCM患者左室心腔内血流流场的变化情况,有望为临床提供一种较为准确检测DCM患者左心功能的新方法。     

Physiological Reduction in Left Ventricular Contractile Function in Healthy Postpartum Women: Potential Overlap with Peripartum Cardiomyopathy

Aims

Peripartum cardiomyopathy is a potentially life-threatening cause of heart failure, commoner in Afro-Caribbean than Caucasian women. Its diagnosis can be challenging due to physiological changes in cardiac function that also occur in healthy women during the early postpartum period. This study aimed to (i) establish the overlap between normal cardiac physiology in the immediate postpartum period and pathological changes in peripartum cardiomyopathy ii) identify any ethnicity-specific changes in cardiac function and cardiac biomarkers in healthy postpartum women.

Methods and Results

We conducted a cross-sectional study of 58 healthy postpartum women within 48 hours of delivery and 18 matched non-pregnant controls. Participants underwent cardiac assessment by echocardiography and strain analysis, including 3D echocardiography in 40 postpartum women. Results were compared with 12 retrospectively studied peripartum cardiomyopathy patients. Healthy postpartum women had significantly higher left ventricular volumes and mass, and lower ejection fraction and global longitudinal strain than non-pregnant controls. These parameters were significantly more impaired in peripartum cardiomyopathy patients but with overlapping ranges of values. Healthy postpartum women had higher levels of adrenomedullin, placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt1) compared to controls. The postpartum state, adrenomedullin, sFlt1 and the sFlt1:PlGF ratio were independent predictors of LV remodelling and function in healthy postpartum women.

Conclusion

Healthy postpartum women demonstrate several echocardiographic indicators of left ventricular remodelling and reduced function, which are associated with altered levels of angiogenic and cardiac biomarkers.     

肺静脉多普勒血流图评价肥厚型心肌病左室舒张功能

为评价肺静脉多普勒血流频谱检测左室舒张功能的价值,我们对２３例正常人和２２例肥厚型心肌病患者进行了研究,结果发现,肥厚型心肌病二尖瓣血流频谱异常者肺静血流谱也能表现异常;在肥厚范围局限的心肌病患者,即使二尖瓣血流频谱正常,肺静脉血流频民可表现异常,特别是ＡＲ峰持续时间和Ｓ波减速时间更有诊断意义,因此用肺静脉血流频率谱评价左室舒张功能不仅交二尖瓣血流图敏感,而且可识别二尖瓣血流图假性正常化,深入研究     

心脏室间隔起搏与右室心尖部起搏对心功能的影响

目的:探讨右心室间隔部(Right Ventricular Septum,RVS)起搏和右心室心尖部(Rightventricularape,RVA)起搏对心功能的影响,为临床提供参考.方法:采用前瞻性研究的方法,对我院自2008年8月-2011年8月收治的行起搏器治疗的72例患者随机均分为实验组和对照组,实验组采用RVS起搏,对照组采用RVA起搏,比较植入后15分钟和1年后测定两组间心室起搏参数差异及血流动力学参数左室射血分数(LVED、每搏量(sv)、心脏指数(CD、二尖瓣血流E峰和A峰最大充盈速度比值(E/A)差异.结果:植入后15分钟和1年后,实验组和对照组起搏参数起搏阈值、电极阻抗、心腔内R波幅度进行比较,差异无统计学意义(P＞0.05).植入后1年后,两组间的血流动力学参数比较,差异有统计学意义(P＜0.05).结论:RVS起搏优于RVA起搏,有望替代传统的右心室心尖部成为最佳的心室起搏部位.     

三维斑点追踪技术对慢性肾功能不全患者左心室收缩功能和右心室功能的评估价值研究

摘要 目的：探讨慢性肾功能不全患者应用三维斑点追踪技术对其左心室收缩功能和右心室功能的评估价值。方法：选择我院收治的慢性肾功能不全患者82例,根据患者肾功能将其分为轻度慢性肾功能不全组[慢性肾脏病（CKD） 2期,47例],中-重度慢性肾功能不全组（CKD 3~5期,35例）,另选取同期医院体检的健康志愿者30例作为对照组,应用二维超声及三维斑点追踪技术检测各组心脏指标,比较三组二维超声指标、三维斑点追踪技术指标,应用受试者工作特征（ROC）曲线分析三维斑点追踪技术对患者左心室收缩功能和右心室功能的评估价值。结果：中-重度慢性肾功能不全组室间隔舒张末期厚度（IVSTd）、肺动脉收缩压（PASP）显著高于轻度慢性肾功能不全组、对照组,右心室面积变化分数（RVFAC）、组织运动三尖瓣环位移（TAPSE）、左心室射血分数（LVEF）显著低于轻度慢性肾功能不全组、对照组（P<0.05）。中-重度慢性肾功能不全组左室整体圆周收缩期峰值应变（LGCS）、左室整体纵向收缩期峰值应变（LGLS）、右室整体圆周收缩期峰值应变（RGCS）右室整体纵向收缩期峰值应变（RGLS）、显著高于轻度慢性肾功能不全组、对照组,左室整体径向收缩期峰值应变（LGRS）、三维左室射血分数（3D-LVEF）、右室整体径向收缩期峰值应变（RGRS）、三维右室射血分数（3D-RVEF）显著低于轻度慢性肾功能不全组、对照组（P<0.05）。ROC曲线分析显示,三维斑点追踪技术对慢性肾功能不全患者左心室收缩功能和右心室功能的评估价值较高。结论：三维斑点追踪技术可以准确检测心脏的纵向运动、圆周运动、径向运动,为临床早期发现慢性肾功能不全患者的心脏功能异常提供依据。     

The Continuity of Right and Left Ventricular Myocardial Sinusoidal Spaces and its Relation to Right Ventricular Implants

Evidence is presented which indicates that blood leaving side branches of an internal mammary artery implanted into the anterior wall of the right ventricle flows from the tunnel in which it lies through myocardial sinusoidal spaces of the anterior right ventricular wall across the midline to fill corresponding spaces in the anterior wall of the left ventricle and thence is carried to the left coronary sinus. The myocardial sinusoidal spaces of right and left ventricles have been well outlined, using injections of polyvinyl acetate and the technique of digestion casts. We have been able to show that there is no barrier between the myocardial sinusoids of the right circulation and those related to the anterior descending branch of the left coronary artery. In structure, these myocardial sinusoidal spaces are quite different from the intramyocardial coronary arteriolar zones which, in 93% of human hearts, are separated from one another without collateral communication.The continuity of the right and left ventricular myocardial sinusoids explains why implantation of a right internal mammary artery into the anterior wall of the right ventricle combined with a corresponding left implant, epicardiectomy and free omental graft, has been so effective in our hands in the treatment of far-advanced human coronary artery insufficiency.     

基于三维超声心动图对比分析扩张型心肌病与二尖瓣关闭不全左室构型和收缩功能的研究

摘要 目的：基于三维超声心动图对比分析扩张型心肌病（DCM）与二尖瓣关闭不全（MI）左室构型和收缩功能的研究。方法：收集我院2018年1月至2021年7月就诊患有左心室（LV）扩张的患者100例,其中DCM患者57例,MI患者43例。LV大小大致相仿,DCM组（43±5）mm/m²,MI组（42±5）mm/m²。另选取同时期50例健康受试者作为对照组。所有患者均进行常规超声心动图及三维超声心动图检查,测量指标主要包括左室大小（LVID）、左室后壁厚度（PWT）、左室舒张末期内径（LVEDD）、左室舒张末期室间间隔厚度（IVS）、左室舒张末期容积（LVEDV）、收缩末期容积（LVESV）、相对室壁厚度（RWT）、LV质量指数（LVMI）、三维左室射血分数（3D-LVEF）、三维舒张末期血流速度（3D-EDV）、二维或三维超声心动图球形指数（2D-SI/3D-SI）。结果：DCM组和MI组LVEDD均大于对照组,差异有统计学意义（P＜0.05）。DCM组比MI组患者心功能分级III/IV和心力衰竭的发生率更高,差异有统计学意义（P＜0.05）。DCM组和MI组患者的LVEDD、LVEDD指数、LVEDV、LVEDV指数、3D-EDV、3D-EDV指数均高于对照组,差异有统计学意义（P＜0.05）;但DCM组和MI组对比差异无统计学意义（P＞0.05）。DCM组和MI组患者的LV长度、LV长度指数、LVMI均高于对照组,差异有统计学意义（P＜0.05）;且MI组高于DCM组,差异有统计学意义（P＜0.05）。DCM组和MI组患者的LVESV、LVESV指数、2D-SI、3D-SI均高于对照组,差异有统计学意义（P＜0.05）;且DCM组高于MI组,差异有统计学意义（P＜0.05）。DCM组3D-LVEF、RWT均低于对照组和MI组,差异有统计学意义（P＜0.05）。ROC分析显示,3D-SI在评估左室扩大患者的左室重构方面优于其他变量,3D-SI的ROC曲线下面积为0.875,95%CI为0.816-0.920,3D-SI>0.62对于DCM和MI区分左室构型的特异性（81.66%）和敏感性（92.09%）较高。DCM和MI患者的3D-LVEF和3D-SI均呈线性负相关（r=-0.719,P=0.000;r=-0.682,P=0.000）。DCM和MI患者3D-SI检测心力衰竭的ROC曲线下面积均大于3D-LVEF的ROC曲线下面积,差异有统计学意义（P=0.000）。结论：与MI患者相比,尽管LV大小大致相仿,但DCM患者的左室几何形状更接近球形,且收缩功能更差。收缩功能与3D-SI显著相关,3D-SI较好地描述了左室重构,可能是LV扩张患者心力衰竭的较强指标。     

Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated,Open-Label,Single-Center,Proof-Of-Concept-Study

Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d) and metformin (2 x 250 mg/d) for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02516085","term_id":"NCT02516085"}}NCT02516085     

Laminins in Peripheral Nerve Development and Muscular Dystrophy

Laminins are extracellular matrix (ECM) proteins that play an important role in cellular function and tissue morphogenesis. In the peripheral nervous system (PNS), laminins are expressed in Schwann cells and participate in their development. Mutations in laminin subunits expressed in the PNS and in skeleton muscle may cause peripheral neuropathies and muscular dystrophy in both humans and mice. Recent studies using gene knockout technology, such as cell-type specific gene targeting techniques, revealed that laminins and their receptors mediate Schwann cell and axon interactions. Schwann cells with disrupted laminin expression exhibit impaired proliferation and differentiation and also undergo apoptosis. In this review, we focus on the potential molecular mechanisms by which laminins participate in the development of Schwann cells.     

Phenotyping of Left and Right Ventricular Function in Mouse Models of Compensated Hypertrophy and Heart Failure with Cardiac MRI

Background

Left ventricular (LV) and right ventricular (RV) function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding mouse model. Therefore, we quantified time-dependent alterations in the ventricular morphology and function in two models of hypertrophy and heart failure and we studied the relationship between RV and LV function during the transition from hypertrophy to heart failure.

Methods

MRI was used to quantify RV and LV function and morphology in healthy (n = 4) and sham operated (n = 3) C57BL/6 mice, and animals with a mild (n = 5) and a severe aortic constriction (n = 10).

Results

Mice subjected to a mild constriction showed increased LV mass (P<0.01) and depressed LV ejection fraction (EF) (P<0.05) as compared to controls, but had similar RVEF (P>0.05). Animals with a severe constriction progressively developed LV hypertrophy (P<0.001), depressed LVEF (P<0.001), followed by a declining RVEF (P<0.001) and the development of pulmonary remodeling, as compared to controls during a 10-week follow-up. Myocardial strain, as a measure for local cardiac function, decreased in mice with a severe constriction compared to controls (P<0.05).

Conclusions

Relevant changes in mouse RV and LV function following an aortic constriction could be quantified using MRI. The well-controlled models described here open opportunities to assess the added value of new MRI techniques for the diagnosis of heart failure and to study the impact of new therapeutic strategies on disease progression and symptom occurrence.     

Impact of Untreated Obstructive Sleep Apnea on Left and Right Ventricular Myocardial Function and Effects of CPAP Therapy

Background

Obstructive sleep apnea (OSA) has deteriorating effect on LV function, whereas its impact on RV function is controversial. We aimed to determine the effect of OSA and continuous positive airway pressure (CPAP) treatment on left and right ventricular (LV, RV) function using transthoracic echocardiography (TTE) and 2 dimensional speckle tracking (2D ST) analysis of RV deformation capability.

Methods and Results

82 patients with OSA and need for CPAP therapy were prospectively enrolled and underwent TTE at study inclusion and after 6 months of follow up (FU). Multivariate regression analysis revealed an independent association between baseline apical right ventricular longitudinal strain (RV-Sl), BMI and the severity of OSA (apical RV-Sl: P = 0.0002, BMI: P = 0.02). After CPAP therapy, LV functional parameters (LVEF: P<0.0001, LV performance index: P = 0.03, stroke volume: P = 0.042), and apical RV-Sl (P = 0.001) improved significantly. The effect of CPAP therapy was related to severity of OSA (LVEF: AHI 5–14, 66.4±8.8%, 68.5±10.6% [P = ns]; AHI 15–30∶59.8±7.7%, 68.6±9.3% [P = 0.002]; AHI>30∶54.1±12.4%, 68.2±13.6%[P<0.0001]; apical RV-Sl: AHI 5–14: −17.3±8.7%, −16.0±10.8% [P = ns], AHI 15–30: −9.8±6.0%, −15.4±10.9% [P = 0.028], AHI>30: −6.3±5.7%, −17.9±11.2% [P<0.0001]).

Conclusions

OSA seems to have deteriorating effect on LV and RV function. We found a beneficial effect of CPAP on LV and RV functional parameters predominately in patients with severe OSA. 2D speckle tracking might be of value to determine early changes in global and regional right ventricular function.     

Pheochromocytoma: A Cause of St-Segment Elevation Myocardial Infarction,Transient Left Ventricular Dysfunction,and Takotsubo Cardiomyopathy

ObjectiveTo report the case of a patient with a pheochromocytoma and apical left ventricular dysfunction that resolved after surgical resection of the pheochromocytoma, to review the effects of catecholamines on myocyte function and the concept that takotsubo cardiomyopathy (TC) is caused by excess catecholamines, and to illustrate the difficulty in the management of an acute coronary syndrome (ACS) during a hypertensive crisis attributable to a pheochromocytoma.MethodsWe present the clinical history, physical findings, laboratory results, and imaging studies in a 60-year-old man with an ACS, TC, and an incidentaloma later diagnosed to be a pheochromocytoma. The association with TC and the pertinent literature are reviewed.ResultsA 60-year-old man was suspected of having myocardial ischemia on the basis of symptoms of paroxysmal chest pain extending to the left shoulder, diaphoresis, ST-segment elevation on an electrocardiogram, and elevated serial levels of cardiac enzymes. Coronary angiography did not reveal substantial coronary artery obstruction but detected ballooning of the apical, anterior, and inferior cardiac walls, consistent with TC. He had a history of labile hypertension and palpitations of 3 months’ duration. An adrenal mass detected on a prior computed tomographic scan and increased 24-hour urine catecholamine levels were consistent with a pheochromocytoma. Treatment with phenoxybenzamine was initiated, and he underwent a right adrenalectomy, which confirmed that the tumor was a pheochromocytoma and dramatically improved the patient’s condition.ConclusionPheochromocytomas manifest with labile blood pressures and should be considered in the differential diagnosis of ACS. This case also supports the concept that TC is caused by excess catecholamines. (Endocr Pract. 2012;18:e77-e80)     

致心律失常性右室心肌病/ 发育不良1 例报告并文献复习

目的:探讨致心律失常性右室心肌病/发育不良的临床特点、病理特征诊断及治疗。方法:回顾性分析1例致心律失常性右室心肌病/发育不良的临床资料,并复习相关文献。结果:致心律失常性右室心肌病/发育不良常见临床表现有心悸、头晕、晕厥、气急胸闷,心电图可见延迟除极epsiton波。结论:致心律失常性右室心肌病/发育不良临床罕见,心脏超声及冠脉CT,心电图为主要确诊手段,治疗以限制运动与药物治疗为主。     

Catheptic and Trypsin-inhibiting Activities in the Nutritional Muscular Dystrophy

From 50 days on, after vitamin E deficient diet was given to guinea pigs, typical symptoms of muscular dystrophy were observed. Muscle protein of these animals was fractionated into 3 fractions, sarcoplasmic fraction, Triton X–100 soluble fraction and myofibrillar fraction.

Free catheptic activity (hemoglobin-splitting activity in the sarcoplasmic fraction), bound catheptic activity (the same in the Triton X–100 soluble fraction) and trypsin-inhibiting activity (in the sarcoplasm fraction) were determined in normal and dystrophic muscles.

In dystrophic muscles, great increase in free and bound catheptic activities was observed.

The increase of free catheptic activity was greater than that of bound catheptic activity.

Trypsin-inhibiting activity was also increased in dystrophic muscles two- or three-fold. At the same time, decrease in the content of myofibrillar protein in dystrophic muscles was observed.

These results were discussed in view of the degradation of protein in dystrophic muscles.