BACKGROUND & AIMS: :Hypertrophic cardiomyopathy (HCM) is a disease characterised by unexplained left ventricular hypertrophy (LVH) (i.e. LVH in the absence of another cardiac or systemic disease that could produce a similar degree of hypertrophy), electrical instability and sudden death (SD).Germline mutations in genes encoding for sarcomere proteins are found in more than half of the cases of unexplained LVH. The autosomal dominant inherited forms of HCM are characterised by incomplete penetrance and variability in clinical and echocardiographic features, prognosis and therapeutic modalities. The identification of the genetic defect in one of the HCM genes allows accurate presymptomatic detection of mutation carriers in a family. Cardiac evaluation of at-risk relatives enables early diagnosis and identification of those patients at high risk for SD, which can be the first manifestation of the disease in asymptomatic persons.In this article we present our experience with genetic testing and cardiac screening in our HCM population and give an overview of the current literature available on this subject. (Neth Heart J 2007;15:184-9.).

背景与目标： 肥厚型心肌病（HCM）是一种以无法解释的左心室肥大（LVH）为特征的疾病（即在没有另一种可能产生类似程度的肥大程度的心脏或全身性疾病的情况下LVH），电不稳定和猝死（SD）。在一半以上的原因不明的LVH病例中发现了编码肌节蛋白的基因突变。 HCM的常染色体显性遗传形式的特征是临床和超声心动图特征，预后和治疗方式的不完全渗透性和变异性。 HCM基因之一中的遗传缺陷的鉴定可以对家庭中的突变携带者进行准确的症状前检测。通过对高危亲属进行心脏评估，可以早期诊断和识别高危SD患者，这可能是无症状患者的首例疾病。在本文中，我们介绍了我们在HCM中进行基因检测和心脏筛查的经验人口，并提供有关该主题的最新文献的概述。 （Neth Heart J 2007; 15：184-9。）。

BACKGROUND & AIMS: :The objective of the present study was to analyse the mode of inheritance for dilated cardiomyopathy (DCM) in Irish wolfhounds using regressive logistic models by testing for mechanisms of genetic transmission. Insights from this spontaneous animal model should aid importantly in understanding basic pathogenic mechanisms with regard to genetics and molecular biology of DCM in humans. Moreover, a procedure for the simultaneous prediction of breeding values and the estimation of genotype probabilities for DCM is expected to markedly improve breeding programmes. Results of cardiovascular examinations of 1018 dogs carried out between 1987 and 2003 by one veterinarian were analysed. Data of 878 dogs from 531 litters in 147 different kennels were used for complex segregation analyses. Pedigree information was available for more than 15 generations. Male dogs were affected significantly more often by DCM than female dogs. The segregation analysis showed that among all other tested models a mixed monogenic-polygenic model including a sex-dependent allele effect best explained the segregation of affected animals in the pedigrees. A pure monogenic inheritance of DCM could be significantly rejected in favour of the major gene and most general model. The gene action of the major gene was significantly different between female and male dogs.

背景与目标： ：本研究的目的是使用回归逻辑模型通过测试遗传传播机制来分析爱尔兰狼狗的扩张型心肌病（DCM）的遗传模式。这种自发动物模型的见解应在理解人类DCM的遗传学和分子生物学方面，对理解基本的致病机制具有重要的帮助作用。此外，用于同时预测育种价值和估计DCM基因型概率的程序有望显着改善育种程序。分析了一名兽医在1987年至2003年之间对1018只狗进行的心血管检查的结果。将来自147个不同犬舍中531窝的878只狗的数据用于复杂的分离分析。谱系信息已有超过15代的历史了。雄性狗受DCM的影响明显多于雌狗。隔离分析表明，在所有其他测试模型中，包括性别依赖性等位基因效应的混合单基因-多基因模型可以最好地解释家系中受影响动物的隔离。 DCM的纯单基因遗传可能会被主要基因和最通用的模型所拒绝。雌性和雄性狗中主要基因的基因作用显着不同。

BACKGROUND & AIMS: BACKGROUND:Although beta blockers (BBs) are established therapy in heart failure, some patients whose left ventricular ejection fraction (LVEF) initially increases on BB therapy experience a subsequent LVEF decline. This study aimed to evaluate the proportion of patients with non-ischemic cardiomyopathy (NICM) whose LVEF declines while on BB therapy and determine important predictors of LVEF decline. METHODS:A retrospective analysis of 238 patients receiving a BB (carvedilol, metoprolol succinate, or tartrate), with an ejection fraction of ≤40% and NICM, whose LVEF initially rose ≥5% after 1 year of BB therapy, was conducted. Post-response LVEF decline ≥5% to a final LVEF of ≤35% was evaluated within 4 years of BB initiation. RESULTS:In our study, we had 52 Caucasians (22%), 78 Hispanics (33%), and 108 African Americans (45%). Overall, 32 patients (13.44 %) had post-response LVEF decline. The nadir LVEF of patients with post-response LVEF decline was 25% (interquartile range 20-27). Compared with others, Hispanics had lower nadir LVEF (22%, p < 0.001). Important predictors of LVEF decline were Hispanic race (odds ratio (OR) 6.094, p < 0.001), New York Heart Association (NYHA) class (OR 2.287, p < 0.05), baseline LVEF (OR 1.075, p < 0.05), and age (OR 0.933, p < 0.001). CONCLUSION:A significant proportion (13.44%) of NICM patients with LVEF increase over 1 year of BB therapy experienced subsequent LVEF decline. Race, NYHA class, baseline LVEF, and age are important predictors of this decline.

背景与目标： 背景：尽管β受体阻滞剂（BBs）已被确立为心力衰竭的治疗方法，但一些在BB治疗中最初增加左心室射血分数（LVEF）的患者经历了随后的LVEF下降。这项研究旨在评估BB治疗时LVEF下降的非缺血性心肌病（NICM）患者的比例，并确定LVEF下降的重要预测指标。
方法：回顾性分析238例接受BB（卡维地洛，美托洛尔琥珀酸盐或酒石酸盐），射血分数≤40％的BB和NICM的患者，这些患者在接受BB治疗1年后LVEF最初升高≥5％。 BB启动后4年内评估反应后LVEF下降≥5％至最终LVEF≤35％。
结果：在我们的研究中，我们有52名高加索人（22％），78名西班牙裔人（33％）和108名非裔美国人（45％）。总体而言，有32例患者（13.44％）的反应后LVEF下降。反应后LVEF下降的患者的最低LVEF为25％（四分位数范围为20-27）。与其他人相比，西班牙裔患者的最低点LVEF较低（22％，p <0.001）。 LVEF下降的重要预测指标是西班牙裔（比值比（OR）6.094，p <0.001），纽约心脏协会（NYHA）级别（OR 2.287，p <0.05），基线LVEF（OR 1.075，p <0.05）和年龄（OR 0.933，p <0.001）。
结论：在BB治疗1年以上的NICM患者中，相当一部分（13.44％）LVEF升高，随后LVEF下降。种族，NYHA等级，基线LVEF和年龄是这一下降的重要预测因素。

BACKGROUND & AIMS: :Objective Dilated cardiomyopathy (DCM) can cause structural and functional changes in the left ventricle (LV). In this study, we evaluated whether cardiac magnetic resonance tissue-tracking (MR-TT) can be applied to the detection of LV abnormalities in patients with DCM. Methods We used MR-TT to analyze the global peak radial strain (GPRS), global peak circumferential strain (GPCS), and global peak longitudinal strain (GPLS) in every segment of the LV in 23 patients with DCM and 25 controls. The LV ejection fraction was also measured as a function indicator. Results Compared with the controls, the GPRS, GPCS, and GPLS were significantly reduced in patients with DCM, indicating global LV function impairment in all directions. We also identified a significant linear correlation between the GPRS, GPCS, and GPLS and the LV ejection fraction, indicating that LV function relies on coordinated wall motion from all directions. Moreover, we found that patients with DCM had a significantly reduced magnitude of the PRS, PCS, and PLS in most segments at different levels, indicating impaired myocardial function in most LV regions. Conclusions Our results demonstrate that LV myocardial strain in patients with DCM can be sensitively detected by MR-TT (not only the global LV function changes but also the segmental strain), which can help to identify the injured segment at an early stage and guide clinical treatment.

背景与目标： ：客观性扩张型心肌病（DCM）会导致左心室（LV）的结构和功能改变。在这项研究中，我们评估了心脏磁共振组织追踪（MR-TT）是否可用于检测DCM患者的左室异常。方法我们使用MR-TT分析了23例DCM患者和25例对照的LV各个部分的总峰值径向应变（GPRS），总峰值周向应变（GPCS）和总峰值纵向应变（GPLS）。左室射血分数也作为功能指标进行了测量。结果与对照组相比，DCM患者的GPRS，GPCS和GPLS明显降低，表明各个方向的整体LV功能受损。我们还发现GPRS，GPCS和GPLS与左室射血分数之间存在显着的线性相关性，这表明左室功能依赖于各个方向的协调壁运动。此外，我们发现DCM患者在不同水平的大多数段中PRS，PCS和PLS的幅度均明显降低，表明大多数LV区的心肌功能受损。结论我们的研究结果表明，MR-TT可以灵敏地检测出DCM患者的左室心肌应变（不仅是整体LV功能改变，而且是节段性应变），这有助于早期识别受损的节段并指导临床治疗。

BACKGROUND & AIMS: BACKGROUND:Diabetes mellitus type 2 (DM2) is a risk factor for developing heart failure but there is no specific therapy for diabetic heart disease. Sodium glucose transporter 2 inhibitors (SGLT2I) are recently developed diabetic drugs that primarily work on the kidney. Clinical data describing the cardiovascular benefits of SGLT2Is highlight the potential therapeutic benefit of these drugs in the prevention of cardiovascular events and heart failure. However, the underlying mechanism of protection remains unclear. We investigated the effect of Dapagliflozin-SGLT2I, on diabetic cardiomyopathy in a mouse model of DM2. METHODS:Cardiomyopathy was induced in diabetic mice (db/db) by subcutaneous infusion of angiotensin II (ATII) for 30 days using an osmotic pump. Dapagliflozin (1.5 mg/kg/day) was administered concomitantly in drinking water. Male homozygous, 12-14 weeks old WT or db/db mice (n = 4-8/group), were used for the experiments. Isolated cardiomyocytes were exposed to glucose (17.5-33 mM) and treated with Dapagliflozin in vitro. Intracellular calcium transients were measured using a fluorescent indicator indo-1. RESULTS:Angiotensin II infusion induced cardiomyopathy in db/db mice, manifested by cardiac hypertrophy, myocardial fibrosis and inflammation (TNFα, TLR4). Dapagliflozin decreased blood glucose (874 ± 111 to 556 ± 57 mg/dl, p < 0.05). In addition it attenuated fibrosis and inflammation and increased the left ventricular fractional shortening in ATII treated db/db mice. In isolated cardiomyocytes Dapagliflozin decreased intracellular calcium transients, inflammation and ROS production. Finally, voltage-dependent L-type calcium channel (CACNA1C), the sodium-calcium exchanger (NCX) and the sodium-hydrogen exchanger 1 (NHE) membrane transporters expression was reduced following Dapagliflozin treatment. CONCLUSION:Dapagliflozin was cardioprotective in ATII-stressed diabetic mice. It reduced oxygen radicals, as well the activity of membrane channels related to calcium transport. The cardioprotective effect manifested by decreased fibrosis, reduced inflammation and improved systolic function. The clinical implication of our results suggest a novel pharmacologic approach for the treatment of diabetic cardiomyopathy through modulation of ion homeostasis.

背景与目标： 背景：2型糖尿病（DM2）是发生心力衰竭的危险因素，但尚无针对糖尿病性心脏病的特异性疗法。葡萄糖转运蛋白2钠抑制剂（SGLT2I）是最近开发的糖尿病药物，主要作用于肾脏。描述SGLT2I的心血管益处的临床数据凸显了这些药物在预防心血管事件和心力衰竭方面的潜在治疗益处。但是，保护的基本机制仍不清楚。我们调查了DM2小鼠模型中Dapagliflozin-SGLT2I对糖尿病性心肌病的影响。
方法：通过渗透泵皮下注射血管紧张素II（ATII）30天，在糖尿病小鼠（db / db）中诱发心肌病。达格列净（1.5 mg / kg /天）在饮用水中同时给药。实验使用12-14周龄的纯合雄性WT或db / db小鼠（n = 4-8 /组）。将分离的心肌细胞暴露于葡萄糖（17.5-33 mM）并在体外用Dapagliflozin处理。使用荧光指示剂indo-1测量细胞内钙瞬变。
结果：血管紧张素Ⅱ输注引起的db / db小鼠心肌病，表现为心脏肥大，心肌纤维化和炎症（TNFα，TLR4）。达格列净降低血糖（874±111至556±57 mg / dl，p <0.05）。另外，在ATII处理的db / db小鼠中，它减轻了纤维化和炎症，并增加了左心室分数的缩短。在分离的心肌细胞中，达格列净降低细胞内钙瞬变，炎症和ROS产生。最后，Dapagliflozin处理后，电压依赖性L型钙通道（CACNA1C），钠钙交换剂（NCX）和钠氢交换剂1（NHE）膜转运蛋白的表达降低。
结论：达格列净对ATII应激的糖尿病小鼠具有心脏保护作用。它减少了氧自由基，以及与钙转运有关的膜通道的活性。心脏保护作用表现为纤维化减少，炎症减少和收缩功能改善。我们结果的临床意义表明，通过调节离子稳态来治疗糖尿病性心肌病的新药理方法。

BACKGROUND & AIMS: :Doppler ultrasound recordings of velocities of flow across the mitral and tricuspid valves and in the hepatic veins, and their variation with respiration, were recorded in seven patients with constrictive pericarditis and in six patients with restrictive cardiomyopathy. Deceleration of mitral and tricuspid flow was also evaluated during apnea. Color flow Doppler was performed in order to evaluate mitral and tricuspid regurgitation. Eight healthy adults served as controls. The patients with constrictive pericarditis showed higher peak diastolic velocities of mitral flow, as well as marked increase of velocity of flow at the onset of expiration and decrease at the onset of inspiration. Reciprocal respiratory variation of the velocities were also observed across the tricuspid valve. The patients with restrictive cardiomyopathy showed moderate or severe mitral and tricuspid regurgitation. They also showed shorter deceleration of flow across the mitral and tricuspid valves during apnea. The pattern of flow in the hepatic veins showed reversal during systole with accentuated reversion during inspiration. These results suggest that patient with constrictive pericarditis and restrictive cardiomyopathy can be differentiated by comparing Doppler echocardiographic data, along with changes induced by respiration.

背景与目标： ：在7例缩窄性心包炎患者和6例限制性心肌病患者中，记录了通过二尖瓣和三尖瓣以及肝静脉的流速的多普勒超声记录及其随呼吸的变化。在呼吸暂停期间还评估了二尖瓣和三尖瓣血流的减速度。进行彩色多普勒检查以评估二尖瓣和三尖瓣关闭不全。八名健康成年人作为对照。缩窄性心包炎患者的二尖瓣血流舒张峰值速度较高，并且在呼气开始时血流速度明显增加，在吸气开始时血流速度明显降低。在三尖瓣上也观察到速度的相互呼吸变化。限制性心肌病患者表现为中度或重度二尖瓣和三尖瓣关闭不全。他们还显示了在呼吸暂停期间，穿过二尖瓣和三尖瓣的血流的减速更短。肝静脉的血流模式在收缩期出现逆转，在吸气时出现明显的逆转。这些结果表明，可以通过比较多普勒超声心动图数据以及呼吸引起的变化来区分患有收缩性心包炎和限制性心肌病的患者。

BACKGROUND & AIMS: :This study was carried out to compare echocardiographic findings of children taking tacrolimus and cyclosporin A (CsA) after orthotopic liver transplantation (OLT). Echocardiograms of 19 children were reviewed during hospitalizations after OLT, and echocardiograms were performed on 23 children who returned to the clinic for a routine follow-up visit after OLT. Measurements were made of the left ventricle (LV) end-diastolic dimension, and of the thickness of the LV free wall (LVFW) and the inter-ventricular septum (IVS). From these measurements, the LV mass was calculated. LV outflow gradient was measured by using Doppler interrogation. Comparisons were made between patients on CsA and patients on tacrolimus. Children with hypertrophic cardiomyopathy (HCM) were identified. Two patients from the in-patient tacrolimus group were found to have HCM. These two patients had asymmetric septal hypertrophy with dynamic LV outflow obstruction and were successfully treated with propranolol, with or without discontinuing tacrolimus. In the out-patient studies, there was no difference in LVFW and IVS thickness, or LV mass index, between children on CsA and children on tacrolimus. Hence, tacrolimus is associated with the development of HCM in children. The effect of tacrolimus on HCM development may be acute and temporary. More data are needed to determine the incidence of HCM in children on tacrolimus therapy and to establish guidelines for clinicians who follow-up these children.

背景与目标： ：本研究旨在比较原位肝移植（OLT）后服用他克莫司和环孢菌素A（CsA）的儿童的超声心动图结果。在OLT住院期间对19例儿童的超声心动图进行了回顾，对23例在OLT后返回诊所进行常规随访的儿童进行了超声心动图检查。测量左心室（LV）舒张末期的尺寸，左心室游离壁（LVFW）和心室间隔（IVS）的厚度。通过这些测量，计算出LV质量。左室流出梯度通过多普勒询问来测量。比较接受CsA的患者和接受他克莫司治疗的患者。确定患有肥厚型心肌病（HCM）的儿童。住院他克莫司组的两名患者被发现患有HCM。这两名患者出现不对称的间隔肥厚，并伴有动态左室流出道梗阻，并成功接受普萘洛尔治疗，无论是否停用他克莫司。在门诊研究中，CsA组儿童和他克莫司组儿童的LVFW和IVS厚度或LV质量指数没有差异。因此，他克莫司与儿童HCM的发展有关。他克莫司对HCM发展的影响可能是急性的和暂时的。需要更多数据来确定他克莫司治疗儿童的HCM发生率，并为随访这些儿童的临床医生建立指导方针。

BACKGROUND & AIMS: :Infantile hypertrophic pyloric stenosis is a common cause of upper gastrointestinal obstruction in infants and presents as projectile, nonbilious emesis in the first few weeks of life. In general, patients with infantile hypertrophic pyloric stenosis are diagnosed after a complete history and physical have been performed augmented by serum electrolyte evaluation, abdominal ultrasound, or upper gastrointestinal barium series. However, some patients can have equivocal radiographic testing and normal serum electrolytes. Two patients are presented in which esophagastroduodenoscopy was used to diagnose previously unsuspected infantile hypertrophic pyloric stenosis.

背景与目标： 小儿肥厚性幽门狭窄是婴儿上消化道梗阻的常见原因，在生命的最初几周表现为弹射性，非胆汁性呕吐。一般而言，婴儿的肥厚性幽门狭窄症是在完整的病史后进行诊断的，并通过血清电解质评估，腹部超声或上消化道钡剂检查增强了身体状况。但是，有些患者的影像学检查结果不明确，血清电解质水平正常。介绍了两名患者，其中食管十二指肠镜被用于诊断先前未曾怀疑的婴儿肥厚性幽门狭窄。

BACKGROUND & AIMS: AIMS:Alcohol septal ablation (ASA) is an established treatment option in hypertrophic obstructive cardiomyopathy (HOCM). ASA is ineffective in some: inaccurate infarct and inability to identify a vessel contribute. We aimed to improve accuracy of infarct using CT angiography guidance and provide a more predictable and satisfactory outcome. METHODS AND RESULTS:Twenty-one successive patients with symptomatic LVOT obstruction refractory to medication underwent CT angiography planning to guide ASA. CT was performed using a dual-source CT system. Alcohol was delivered to the artery identified from CT: in 17/21 this was a sub-branch of a septal artery, in 2/21 the septal vessel was identified from the circumflex artery. Peak gradient improved from 98 (IQR 89.50-111.50) mmHg to 14 (IQR 8.50-22) mmHg (p=0.003). Systolic anterior motion (SAM) improved in 18/20 patients. NYHA class improved by ≥1 in 18/20. Peak VO2 improved from 79.19% of predicted value (±14.01) to 91.62% (±12.02) predicted (p<0.0001). Success at the first procedure is greater with CT guidance, 17/20 vs. 50/75 with traditional methods (pre-CT guidance) (p=0.02); 9/20 had six-month CMR with target septum infarct in all. ASA-related RBBB reduced from 62% to 13% (p=0.0004). CONCLUSIONS:CT angiography planning improves localisation of infarct and procedural success at the first attempt in ASA when compared to traditional methods. Follow-up to six months suggests a symptomatic, functional and haemodynamic improvement.

背景与目标： 目的：酒精中隔消融（ASA）是肥厚性梗阻性心肌病（HOCM）的既定治疗选择。 ASA在某些方面无效：不正确的梗塞和无法识别血管。我们旨在使用CT血管造影指导提高梗塞的准确性，并提供更可预测和令人满意的结果。
方法和结果：21例因药物难治性LVOT梗阻的连续患者接受了CT血管造影计划，以指导ASA。使用双源CT系统进行CT。酒精被输送至通过CT识别的动脉：在17/21中，这是隔动脉的一个分支，在2/21中，是从回旋支动脉中识别出了间隔血管。峰梯度从98（IQR 89.50-111.50）mmHg提高到14（IQR 8.50-22）mmHg（p = 0.003）。 18/20例患者的收缩前运动（SAM）有所改善。 NYHA等级在18/20中提高了≥1。 VO2峰值从预测值的79.19％（±14.01）提高到预测值的91.62％（±12.02）（p <0.0001）。 CT引导下第一次手术的成功率更高，传统方法为17/20，而传统方法为50/75（CT引导前）（p = 0.02）； 9/20进行了为期六个月的CMR，总共有目标隔梗塞。与ASA相关的RBBB从62％降低到13％（p = 0.0004）。
结论：与传统方法相比，CT血管造影规划可在ASA首次尝试时改善梗塞的局限性和手术成功率。六个月的随访表明症状，功能和血流动力学均有改善。

BACKGROUND & AIMS: :This study was aimed at identifying predictive variables for recurrence of mitral regurgitation (MR) in patients with dilated cardiomyopathy (DCM) undergoing mitral valve (MV) repair. From January 1997 to December 2005, 142 patients with DCM, 105 (73.9%) ischemic and 37 (26.1%) non-ischemic, underwent MV repair. Mean age was 66+/-10 years and mean MR grade was 3.2+/-0.7 (scale 1+ to 4+). Ninety-seven (71% ischemic, 29% non-ischemic), out of 98 still alive at follow-up, were included in this retrospective analysis. In all cases MV posterior annuloplasty was performed; all patients were followed-up by echocardiography (mean time interval of 44+/-28 months) to evaluate MR recurrence (>or=2+/4+). Thirty-day mortality was 9.2% (13 patients). Mean MR grade at follow-up was 0.9+/-0.9. Four-year freedom from MR recurrence was 65.5%+/-8.3. Cox analysis showed left ventricular end-diastolic volume index (LVEDVi, OR=1.03, P=0.016, AUC=0.72), left ventricular end-systolic volume index (LVESVi, OR=1.03, P=0.033, AUC=0.71), left ventricular ejection fraction (LVEF, OR=0.82, P=0.001, AUC=0.72), mitral valve coaptation depth (MVCD, OR=1.6, P=0.017, AUC=0.72) to be predictive variables for MR recurrence. Preoperative left ventricular dilatation and function along with degree of papillary muscle displacement can be helpful in identifying patients with higher probability to undergo a durable MV repair.

背景与目标： ：本研究旨在确定接受二尖瓣（MV）修复的扩张型心肌病（DCM）患者二尖瓣关闭不全（MR）复发的预测变量。从1997年1月至2005年12月，对142例DCM，105例（73.9％）缺血和37例（26.1％）非缺血性DCM患者进行了MV修复。平均年龄为66 / -10岁，平均MR评分为3.2 /-0.7（等级1至4）。这项回顾性分析包括了98例随访中仍存活的98例（缺血性占71％，非缺血性占29％）。在所有情况下，均进行了MV后瓣成形术；所有患者均接受超声心动图随访（平均时间间隔为44 / -28个月）以评估MR复发（>或= 2/4）。 30天死亡率为9.2％（13例患者）。随访时的平均MR等级为0.9 /-0.9。 MR复发的四年自由度为65.5％/-8.3。 Cox分析显示左室舒张末期容积指数（LVEDVi，OR = 1.03，P = 0.016，AUC = 0.72），左室收缩末期容积指数（LVESVi，OR = 1.03，P = 0.033，AUC = 0.71），左心室射血分数（LVEF，OR = 0.82，P = 0.001，AUC = 0.72），二尖瓣接合深度（MVCD，OR = 1.6，P = 0.017，AUC = 0.72）是MR复发的预测变量。术前左心室扩张和功能以及乳头状肌移位的程度可有助于确定接受持久性MV修复的可能性更高的患者。

BACKGROUND & AIMS: :Hypertrophic cardiomyopathy (HCM) is a prevalent and untreatable cardiovascular disease with a highly complex clinical and genetic causation. HCM patients bearing similar sarcomeric mutations display variable clinical outcomes, implying the involvement of gene modifiers that regulate disease progression. As individuals exhibiting mutations in mitochondrial DNA (mtDNA) present cardiac phenotypes, the mitochondrial genome is a promising candidate to harbor gene modifiers of HCM. Herein, we sequenced the mtDNA of isogenic pluripotent stem cell-cardiomyocyte models of HCM focusing on two sarcomeric mutations. This approach was extended to unrelated patient families totaling 52 cell lines. By correlating cellular and clinical phenotypes with mtDNA sequencing, potentially HCM-protective or -aggravator mtDNA variants were identified. These novel mutations were mostly located in the non-coding control region of the mtDNA and did not overlap with those of other mitochondrial diseases. Analysis of unrelated patients highlighted family-specific mtDNA variants, while others were common in particular population haplogroups. Further validation of mtDNA variants as gene modifiers is warranted but limited by the technically challenging methods of editing the mitochondrial genome. Future molecular characterization of these mtDNA variants in the context of HCM may identify novel treatments and facilitate genetic screening in cardiomyopathy patients towards more efficient treatment options.

背景与目标： 肥厚型心肌病（HCM）是一种普遍存在且无法治愈的心血管疾病，具有高度复杂的临床和遗传原因。携带相似肌节突变的HCM患者显示出可变的临床结果，这暗示着调节疾病进展的基因修饰剂的参与。由于在线粒体DNA（mtDNA）中表现出突变的个体表现出心脏表型，因此线粒体基因组是保留HCM基因修饰子的有前途的候选者。在本文中，我们对着重于两个肌节突变的HCM等基因多能干细胞-心肌细胞模型的mtDNA进行了测序。该方法已扩展到无关的患者家族，共52个细胞系。通过将细胞和临床表型与mtDNA测序相关联，鉴定出潜在的HCM保护性或加重性mtDNA变异体。这些新颖的突变大多位于mtDNA的非编码控制区域，并且与其他线粒体疾病的重叠。对不相关患者的分析突出显示了家庭特定的mtDNA变异，而其他变异在特定人群单倍体中很常见。 mtDNA变异体作为基因修饰剂的进一步验证是有保证的，但受到编辑线粒体基因组的技术挑战性方法的限制。在HCM背景下，这些mtDNA变体的未来分子表征可能会发现新颖的治疗方法，并有助于对心肌病患者进行基因筛查，以寻求更有效的治疗选择。

BACKGROUND & AIMS: PURPOSE:In patients with systolic heart failure, the ability of cardiopulmonary exercise testing (CPX) variables to reflect pathophysiology is well established. The relationship between CPX and pathophysiology has, however, not been thoroughly investigated in patients with nonobstructive hypertrophic cardiomyopathy (NHCM). The objective of this study was to assess the ability of CPX variables to reflect resting hemodynamics in patients with nonobstructive hypertrophic cardiomyopathy NHCM. METHODS:We performed CPX and right heart catheterization on 83 subjects with NHCM (51 male/32 female, mean age = 38 +/- 10 yr, NYHA I-III mean = 1.7). Peak oxygen consumption ( O2) and minute ventilation/carbon dioxide ratio (V E/VCO2) at peak exercise were compared to resting hemodynamics including pulmonary artery systolic, diastolic and mean pressures (PASP, PADP and MPAP), and pulmonary capillary wedge pressure (PCWP). RESULTS:Elevations in PCWP (> or = 15 mm Hg), PASP (> or =30 and > or = 40 mm Hg), PADP (> 15 mm Hg) and MPAP (> or = 20 mm Hg) were detected in 22, 33, 10, and 23% of subjects, respectively. Peak V E/VCO2 (positive correlation) and peak VO2 (negative correlation) correlated modestly with all pressure measurements (r = 0.33-0.51, P < 0.01 for all measurements). By receiver operating curve analysis, a V E/VCO2 >35.5 exhibited the best diagnostic accuracy with a curve areas of 0.81 for PAP > or = 30 mm Hg (sensitivity/specificity = 86%/67%), 0.87 for PAP > or = 40 mm Hg (77%/100%), 0.86 for MPAP > 20 mm Hg (83%/79%), and 0.84 for PCWP > or = 15 mm Hg (80%/76%). CONCLUSIONS:CPX can accurately identify abnormal resting hemodynamics in patients with NHCM. Further testing of this modality in other forms of diastolic dysfunction may be warranted.

背景与目标： 目的：在收缩性心力衰竭患者中，心肺功能测试（CPX）变量反映病理生理的能力已得到充分确立。然而，尚未在非阻塞性肥厚型心肌病（NHCM）患者中彻底研究CPX与病理生理学之间的关系。这项研究的目的是评估CPX变量反映非阻塞性肥厚型心肌病NHCM患者静息血流动力学的能力。
方法：我们对83例NHCM患者（51例男性/ 32例女性，平均年龄= 38/10年，NYHA I-III平均值= 1.7）进行了CPX和右心导管检查。将峰值运动时的峰值耗氧量（O2）和分钟通气/二氧化碳比（VE / VCO2）与静息血液动力学进行比较，包括肺动脉收缩压，舒张压和平均压力（PASP，PADP和MPAP）以及肺毛细血管楔压（PCWP） ）。
结果：在22中检测到PCWP（>或= 15 mm Hg），PASP（>或= 30 and>或= 40 mm Hg），PADP（> 15 mm Hg）和MPAP（>或= 20 mm Hg）升高。 ，分别占33％，10％和23％的受试者。峰值V E / VCO2（正相关）和峰值VO2（负相关）与所有压力测量值均呈适度相关（r = 0.33-0.51，所有测量值P <0.01）。通过接收器工作曲线分析，VE / VCO2> 35.5表现出最佳的诊断准确性，PAP>或= 30 mm Hg的曲线面积为0.81（灵敏度/特异性= 86％/ 67％），PAP>或= 40的曲线面积为0.87毫米汞柱（77％/ 100％），MPAP> 20毫米汞柱（83％/ 79％）为0.86，PCWP>或= 15毫米汞柱（80％/ 76％）为0.84。
结论：CPX可以准确识别NHCM患者的异常静息血液动力学。可能需要对其他形式的舒张功能障碍的这种方式进行进一步测试。

BACKGROUND & AIMS: :Gamma-delta T-cells are usually minor component of peripheral blood and lymphoid tissues, but may play an important role in autoimmune diseases. We here describe the first case of dilated cardiomyopathy (DCM) with heart infiltration by mostly gamma-delta T-cells, who improved significantly by steroid therapy. In general, steroid therapy has only a little effect on DCM, however these findings might have implications with respect to the selection of patients who might respond to immunosuppressive therapy.

背景与目标： γ-δT细胞通常是外周血和淋巴组织的次要成分，但可能在自身免疫性疾病中起重要作用。我们在这里描述了第一例扩张型心肌病（DCM），其主要由大部分γ-δT细胞引起的心脏浸润，通过类固醇疗法可显着改善。通常，类固醇疗法对DCM的影响很小，但是这些发现可能对选择可能对免疫抑制疗法有反应的患者产生影响。

BACKGROUND & AIMS: Hypertrophic cartilage from the tibiotarsus of Day 20 chick embryonic tibiae was found to contain an unusually high concentration of lysylpyridinoline (LP), a nonreducible collagen cross-link normally found only in bone and dentin but not in cartilage. Since type X collagen is abundant in this cartilage, research was conducted to see if type X was the primary source of LP. The 45-kDa pepsin-resistant form of type X was purified by immunoaffinity chromatography. It contained a high concentration of the LP cross-link while type II contained primarily hydroxylysylpyridinoline (HP), the predominant cross-link in cartilage. This, to our knowledge is the first time that type X has been shown directly to form nonreducible cross-links and that a collagen other than type I has a high level of LP. Also, it is interesting that the HP and LP cross-links are found in a collagen that is degraded so rapidly. Possible explanations for these findings are discussed.

背景与目标： 发现来自第20天雏鸡胫骨胫骨的肥大性软骨中含有异常高浓度的赖氨酰吡啶啉（LP），这是一种不可还原的胶原交联键，通常仅在骨骼和牙本质中存在，而在软骨中不存在。由于X型胶原在该软骨中含量丰富，因此进行了研究以查看X型是否是LP的主要来源。通过免疫亲和色谱纯化X型的45 kDa胃蛋白酶抗性。它包含高浓度的LP交联，而II型则主要包含羟基糖基吡啶啉（HP），这是软骨中的主要交联。据我们所知，这是首次直接显示X型形成不可还原的交联，并且I型以外的胶原蛋白具有较高的LP水平。同样，有趣的是，在降解得如此迅速的胶原蛋白中发现了HP和LP交联。讨论了这些发现的可能解释。

BACKGROUND & AIMS: :A 56-year-old asymptomatic man was referred for further evaluation because he displayed a rapid T-wave change on the ECG, from positive T waves to giant negative T waves in the anterolateral precordial leads, within 2 years. Transthoracic echocardiography revealed mild left ventricular apical hypertrophy without obstruction. Cardiac magnetic resonance imaging showed apical hypertrophic cardiomyopathy with focal hyperenhancement of the non-hypertrophic basal lateral segment of the left ventricle and absence of hyperenhancement of the hypertrophied apical segments.

背景与目标： ：一名56岁无症状男子被转诊作进一步评估，因为他在2年内在心电图上显示了快速的T波变化，从前外侧心前导中的正T波变为巨大的负T波。经胸超声心动图检查发现左心室轻度肥厚，无梗阻。心脏磁共振成像显示心尖肥厚型心肌病，左心室非肥厚性基底外侧节局灶性增强，而肥厚型心尖节未增强。