Takotsubo-like cardiomyopathy in pheochromocytoma

Background

Takotsubo Cardiomyopathy (TTC) is commonly triggered by acute illness, physical or emotional stress and has been associated with elevated catecholamine levels. TTC has also been associated with pheochromocytoma (TTC-pheo).

Methods

We performed a computer assisted search of the electronic databases Medline, Scopus and Google Scholar from 1965 to January 2011. All case reports with reported TTC-pheo were selected and compared to a recent review by Gianni et al. which examined primary TTC (TTC-primary).

Statistics

Data analysis was performed using SPSS version 18. Chi-square test of Fisher's exact test was used as appropriate to compare categorical data.

Results

38 cases of TTC-pheo were retrieved from literature and compared to 254 cases of TTC-p. Chest pain was the most common presentation in both groups. The TTC-pheo patients were on average 18 years younger than patients with TTC-p (p < 0.01). Only a minority of TTC-pheo patients presented with classical features of pheochromocytoma including hypertension (52.6%), headache (28.9%), palpitations (31.6 %), and diaphoresis (26.3%). In TTC-pheo complications rates were higher compared to TTC-p, including cardiogenic shock (34.2% vs. 4.2%, p < 0.01) and heart failure (46.7% vs. 17.7%, p < 0.01). Antecedent stressors were less common in TTC-pheo. About one-third of TTC-pheo patients presented with the inverted pattern, which compared to the apical pattern, was associated with higher complication rates, including, cardiogenic shock, heart failure, acute renal failure and arrhythmias.

Conclusions

Although rare, pheochromocytoma should be considered in the differential diagnosis of TTC especially in younger patients presenting without antecedent stressors and a high complication rate. The similarities in the clinical features and outcomes in patients with TTC-p and TTC-pheo point to a similar underlying cardiac pathophysiologic process at the time of the acute presentation.     

扩张型心肌病的心电图改变

目的观察扩张型心肌病病例的心电图改变。方法26例经心脏超声检查诊断为扩张型心肌病的病例列入观察。分析结果显示所有病例心电图均有异常改变,其中以一度房室阻滞最为常见(35%),其次是ST段下移(31%)和心房颤动(26%)。对心电图各波段测定,显示QRS时限延长明显(115±34.5ms),与心脏超声检查测定的左室大小呈线性正相关。结论提示对于心电图出现QRS时限延长,或一度房室阻滞或ST段下移或心房颤动者,有必要进行心脏超声检查。     

Defect in the adrenergic receptor-adenylate cyclase system during development of catecholamine-induced cardiomyopathy

We have investigated alterations in adrenergic receptors and adenylate cyclase activity in cardiac membranes from rats injected with 40 mg/kg intraperitoneal isoproterenol. Reduction in the number of beta-adrenergic and alpha-adrenergic receptors, as assessed by changes in specific binding of 3H-dihydroalprenolol (DHA) and 3H-dihydroergocryptine (DHE), was observed only at 9 and 24 hours after isoproterenol injection, respectively. On the other hand, epinephrine-stimulated, NaF-stimulated, and Gpp (NH)p-stimulated adenylate cyclase activity was decreased as early as 3 hours after isoproterenol treatment without changes in the basal adenylate cyclase activity. These results demonstrate a defect in the adrenergic receptor-adenylate cyclase system during the development of catecholamine-induced cardiomyopathy and may partly explain the attenuated inotropic adrenergic response of the heart under stressful situations.     

Impaired myocardial performance and response to calcium in experimental alcoholic cardiomyopathy

The effect of chronic consumption of ethanol upon myocardial function has been in dispute. The mechanical performance of isolated left ventricular papillary muscles was studied in a group of eight male rats which had been on a diet in which ethanol provided 36% of total calories for 5 weeks. This group was compared to a pairfed control group of eight rats. Muscles were studied in oxygenated Krebs-Henseleit solution at 28°C, while stretched to L_max and stimulated at 12/min to contract isometrically. Bath calcium concentrations were varied from 1.25 to 7.5 mm/l. Heart size and chamber weights did not differ between the groups. Peak developed tension, maximum rates of rise and fall of tension, and time to half relaxation were significantly lower in the ethanol group, whereas resting tension and time to peak tension did not differ in the two groups. All parameters except time to half relaxation exhibited a significant dependence on concentration of calcium in the bath. However, the degrees of augmentation of peak developed tension and maximum rates of rise and fall of tension with increase in calcium in the bath from 1.25 to 2.5 mm/l were significantly lower in the ethanol group. In addition to impairment of function with chronic alcohol administration, altered sensitivity to calcium was demonstrated. Thus, isolated muscle studies have defined a defect in defined a defect in myocardial performance not apparent from studies of hemodynamics in the intact animal.     

Endomyocardial biopsy in right ventricular cardiomyopathy

Right ventricular cardiomyopathy is characterized by a progressive myocyte loss and fibro-fatty substitution of the right ventricle. The aim of our study was to assess the diagnostic accuracy of right ventricular endomyocardial biopsy. Using an imaging analyser system, histomorphometric parameters of myocytes, interstitium, fibrous tissue and fatty tissue were evaluated on endomyocardial biopsy from 30 patients with arrhythmogenic right ventricular cardiomyopathy, 29 patients with dilated cardiomyopathy and 30 control patients. The percent area of myocytes decreased from 78.10 ± 7.34 in control to 63.39 ± 9.22 in dilated cardiomyopathy (P < 0.05) and to 47.28 ± 15.01 in arrhythmogenic right ventricular cardiomyopathy (P < 0.01). Fibrous tissue increased from 8.10 ± 3.89 in control to 21.80 ± 9.29 in dilated cardiomyopathy (P < 0.05) and to 24.60 ± 11.37 in arrhythmogenic right ventricular cardiomyopathy (P < 0.05). Fatty tissue varied from 0.33 ± 1.44 in control and 0.07 ± 0.31 in dilated cardiomyopathy to 13.30 ± 17.30 in arrhythmogenic right ventricular cardiomyopathy (P < 0.05). Fatty tissue was a feature of arrhythmogenic right ventricular cardiomyopathy (67% of patients vs. 6% of control and dilated cardiomyopathy patients). Diagnostic values typifying arrhythmogenic right ventricular cardiomyopathy, obtained by excluding any overlapping between confidence intervals in the three groups, were: myocytes <44.95%; fibrous tissue >40.38%, and fatty tissue >3.21%, with 67% sensitivity and 91.53% specificity for at least one parameter. In conclusion, a significant difference between arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and control exists in terms of amount of myocytes, fibrous tissue and fatty tissue. Presence of fatty tissue and fibrous tissue exceeding 3.21% and 40.38%, respectively should be considered highly suspect for arrhythmogenic right ventricular cardiomyopathy in right ventricular endomyocardial biopsy.     

Immunological analysis of auto-antibodies against the adenine nucleotide translocator in dilated cardiomyopathy

We have previously identified the adenine nucleotide translocator (ANT), an intrinsic protein of the inner mitochondrial membrane, as an auto-antigen in dilated cardiomyopathy (DCM). Further immunochemical characterization by crossed immunoelectrophoresis, indirect solid phase radioimmunoassay and immunoadsorption studies on the isolated translocator protein and mitochondria from heart, kidney and liver showed the existence of organ-specific antigenic determinants although partial crossreactivity between the three proteins was observed. Sera from 18 patients with histologically proven dilated cardiomyopathy were studied for their capacity to bind to the translocator protein. Seventeen of 18 patients showed significant binding, while in the sera of patients with coronary heart disease, suspected alcoholic heart disease or healthy blood donors, no anti-ANT antibodies were observed. Further studies showed organ-specific and functionally active autoantibodies, which decreased the ADP/ATP exchange rate from heart mitochondria. A close correlation was found between the antibody-titer and the hemodynamic function. These results give new evidence for autoimmunological events in dilated cardiomyopathy.     

扩张型心肌病免疫调节性T细胞的改变及其活化

目的探讨扩张型心肌病兔疫调节性T细胞的改变及其活化.方法采取28例扩张型心肌病患者外周静脉血，分离白细胞，单克隆免疫荧光抗体技术标记CD3，CD4，CD8，CD45RO，CD30，CD25，CD69，CD45及CD14，用流式细胞术检测扩张型心肌病患者血中不同T淋巴细胞亚群比例及其各活化分化抗原的膜表达情况，并与其它原因心衰组及正常对照组进行对比。结果扩张型心肌病CD8＋T细胞百分率下降，CD4＋／CD8＋细胞比值升高，CD8CD69双阳性T细胞百分率增加，CD4＋细胞的CD25，CD45RO表达阳性细胞数增加。结论扩张型心肌病T淋巴细胞亚群比例失衡，Ts细胞在数量上及功能上都有改变，Th细胞活化增加，揭示T细胞免疫调节功能紊乱是扩张型心肌病自身免疫过程的关键因素。     

Levosimendan suppresses oxidative injury,apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy

Diabetic cardiomyopathy plays a major role in morbidity and mortality among cardiovascular disorder-related complications. This study was designed to explore long-term benefits of Levosimendan (LEVO) along with Ramipril and Insulin. Diabetic cardiomyopathy was induced using streptozotocin (STZ) at the dose of 25?mg/kg/body weight/day for three consecutive days in Wistar rats. Rats were randomly divided into 10 groups and treatments were started after 2 weeks of STZ administration. A gradual but severe hyperglycemia (^§§§p?<?0.001) was observed in all STZ-treated groups except those received insulin (2 U/day). LEVO alone and in combination with Ramipril and Insulin normalized (**p?<?0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p?<?0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment. Myofibril degeneration, mitochondrial fibrosis and vacuolization occurred after STZ treatment, were also reversed by LEVO in combination with Ramipril and Insulin. The combination of LEVO with Ramipril and Insulin improved hemodynamic functions, maintained cardiac enzymes and ameliorated myofibril damage in diabetic cardiomyopathy.     

扩张型心肌病12导联动态心电图分析

目的观察扩张型心肌病的24h12导联动态心电图改变。方法60例经心脏超声检查诊断为扩张型心肌病的病例入选，并行24h12导联动态心电图监测。结果所有病例动态心电图均有异常改变，其中以室性早搏为最常见（97％），其次是ST-T改变（60％）和室性心动过速（50％）。心功能越差，复合心律失常越多见。结论扩张型心肌病的心律失常发生率高且多样，有复合心律失常的患者有必要进行心脏超声心动图检查。     

Myocardial histological changes in dilated cardiomyopathy during a long-term left ventricular assist device support

Summary As the myocardium in patients with dilated cardiomyopathy (DCM) is deteriorating progressively, resulting in a decrease in left ventricular function, patients with end-stage DCM may require implantation of a left ventricular assist device (LVAD) unless they undergo heart transplantation. Although LVAD has been reported to provide excellent hemodynamic support, no data are currently available about the effects of long-term LVAD support on the myocardium in patients with DCM. We describe two patients with end-stage DCM who underwent LVAD implantation and were supported with LVAD for 524 and 245 days, respectively. Serial myocardial biopsies showed increases in myocardial cell diameter and intercellular fibrosis, despite excellent hemodynamic support by LVAD. These data suggest that the myocardium in patients with end-stage DCM deteriorates progressively, even if the preload of the left ventricle is reduced by LVAD.     

肥厚型心肌病的心电图改变

目的 探讨肥厚型心肌病患者心电图变化及其临床意义。方法 对44例肥厚型心肌病(Ⅰ型前间隔肥大14例，Ⅱ型前间隔、后间隔均肥大18例，Ⅲ型左心室前壁或／和侧壁、后壁肥大7例，Ⅳ型心尖部肥大5例)行常规12导联心电图检查。结果 心电图异常(ST-T改变、异常Q波、心室肥大等)发生率为93．2％。Ⅳ型ST-T改变多见于前侧壁、高侧壁，具有特殊性。其它三型患者异常Q波、ST-T改变发生率及部位差异均无显著性意义。结论 肥厚型心肌病患者大多存在不同程度的心电图异常，但除心尖肥厚型心肌病外，其他各型心电图改变无特异性。     

Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy

Genes encoding Ca(2+) regulatory proteins responsible for Ca(2+) homeostasis have been suggested as possible candidates for FHC. Mutations in sarcomere genes account for approximately 50% of all FHC cases indicating other genes, including those involved in Ca(2+) handling, may account for the remainder. The aim of this study was to identify causative mutations in genes involved in Ca(2+) regulation in patients with familial hypertrophic cardiomyopathy (FHC). An Australian cohort of 252 unrelated familial hypertrophic cardiomyopathy patients were screened for mutations in the Ca(2+) regulatory genes, sorcin (SRI), calstabin (FKBP1B), calsequestrin (CASQ2), phospholamban (PLN), sarcolipin (SLN), calreticulin (CALR3) and calmodulin (CALM). A total of 17 exonic DNA variants were identified in the 7 Ca(2+) regulatory genes studied, of which 4 were considered of pathogenic significance. Two novel mutations in the CALR3 gene were identified (Lys82Arg, Arg73Gln) and one truncation mutation in the PLN gene (Leu39Ter). A variant was also identified in the CASQ2 gene (Asp63Glu). These four variants were all novel, resulted in changes in conserved amino acids and were not identified in a normal population. In conclusion, mutations in Ca(2+) handling genes are an infrequent but important cause of FHC. DNA variants in Ca(2+) genes may also be involved as modifying factors in phenotype development. Further evaluation of the role of defects in Ca(2+) regulation will shed light on the molecular pathogenesis of FHC.     

Creatine kinase isoforms as circulating markers of deterioration in idiopathic dilated cardiomyopathy

Background: A proportion of patients with dilated cardiomyopathy (DCM) may have ongoing myocardial damage secondary to viral or immune mediated myocardial inflammation. Hypothesis: The prognostic determinants identify patients with decreased survival but do not provide a measure of myocardial damage. To obtain an objective assessment of myocardial damage in DCM, we measured plasma levels of creatine kinase (CK), its isoenzymes (CK-MM and CK-MB), and separated the isoforms of CK-MM and CK-MB. Methods: The cohort consisted of 77 consecutive patients (61 men, 16 women) with DCM (World Health Organization criteria), aged 49 ± 14 years (range 19–60). Patients had been symptomatic for 29 ± 38 months (range 0.5–200 months) with 48 in New York Heart Association class I/II and 29 in class III/IV at the time of diagnosis. During median follow-up of 27 months from diagnosis (range 0.6–165), 50 patients remained clinically stable and 27 had deteriorated. Results: A significantly higher proportion of patients with DCM had abnormal MB2/MB1 ratio compared with normal volunteers (11,14% vs. 1, 1%, p = 0.003). Patients who deteriorated had higher MB2/MB1 ratio, (1.22 ± 0.62 vs. 0.85 ± 0.56;p = 0.01), and more frequently had abnormal MB2/ MB1 ratio (8,30% vs. 3,6%;p=0.004) and CK and CK-MM activities (5, 19% vs. 2, 4%;p = 0.03) than those who remained stable. Patients with DCM with high CK-MB activity had 3.13-fold increased odds of sudden death or need for cardiac transplantation (95% confidence interval 1.53–6.40, p = 0.008). Thus, CK measurements, in particular CK-MB isoforms, are markers of myocardial damage in a subset of patients with DCM and could be useful in investigating the possibility of persistent myocardial damage in these patients.     

Sudden death during pregnancy in hypertrophic cardiomyopathy.

A 27-year-old asymptomatic woman became pregnant 6 months after a diagnosis of hypertrophic cardiomyopathy and was well until 28 weeks' gestation when she died suddenly while running up stairs. The potential pathophysiological mechanisms of sudden death during pregnancy in hypertrophic cardiomyopathy, as well as the diagnostic and therapeutic implications, are discussed.     

肥厚型心肌病左心房功能改变的超声研究

目的用超声声学定量(AQ)技术研究肥厚型心肌病(HCM)左心房结构与功能的改变。方法将辽宁省人民医院2004年7月至2005年10月门诊及住院患者进行分组,其中肥厚型梗阻性心肌病组27例,肥厚型非梗阻性心肌病组29例,另选健康体检者30名作为对照组。采用AQ技术,测量左心房快速排空分数(LAEF)、峰值快速排空率(PRER);左心房存储容积(RV)和峰值充盈率(PFR)、左心室收缩末期左心房容量(ESV);左心房主动收缩排空分数(AEF)和峰值心房排空率(PAER)。结果与对照组比较,HCM组左心房LAEF减低;RV和PFR增高;AEF和PAER增加。结论HCM组峰值左房管道功能减低,助力泵功能和储存器功能代偿性增强,AQ技术为左心房功能的评价提供了无创性新方法。     

二维斑点成像技术评价扩张型心肌病患者心脏的纵向扭转

目的 运用二维斑点成像技术评价扩张型心肌病患者(dilated cardiomyopathy,DCM)与健康人间各参数的差异,证实DCM患者心脏纵向扭转的存在.方法 搜集温州医学院附属第一医院2008年6月至2009年9月期间就诊的42例DCM患者作为DCM组和35例健康人作为对照组.两组均行常规超声心动图,检测左心房内径、左心室射血分数、过二尖瓣口舒张早期血流速度及舒张晚期血流速度.应用GE Echopac软件测量得到DCM组和对照组患者心尖四腔心的左心室壁的径向应变、应变率,左心室侧壁、室间隔、心尖及左心室整体纵向峰值扭转角度,对比两组间各参数的差异.结果 (1) DCM组患者左心房内径、左心室收缩末期容积及左心室舒张末期容积均明显大于对照组(P均＜0.01),左心室射血分数明显低于对照组(P＜0.0l),过二尖瓣口舒张早期血流峰速度/舒张晚期血流峰速度两组比较差异无统计学意义(P＞0.05).(2) DCM组患者径向收缩期峰值应变以及收缩期、舒张早期、舒张晚期径向峰值应变率均明显低于对照组(P均＜0.01).(3)对照组左心室侧壁的中间段、基底段以及心尖段呈逆时针扭转,而室间隔的基底段、中间段呈顺时针扭转,DCM组患者左心室侧壁的中间段呈逆时针扭转,而左心室侧壁基底段、心尖段、室间隔的基底段及中间段均呈顺时针扭转.DCM组患者左心室侧壁中间段和基底段、心尖段以及室间隔基底段的扭转角度均明显低于对照组(P均＜0.01).对照组左心室呈较小角度的纵向逆时针扭转(0.76°±2.63°),而DCM组患者左心室呈纵向顺时针扭转(- 1.58°±3.42°),两组扭转角度的差异有统计学意义(P＜0.01).(4)DCM组患者左心室侧壁基底段、中间段与室间隔基底段扭转达峰时间差均与左心室的纵向峰值扭转角度具有相关性(r=0.409,P=0.007; r=0.396,P=0.009).结论 应用二维斑点成像技术,通过分析各节段应变、应变率及纵向扭转角度等参数,证实DCM患者心脏存在着一定角度的纵向顺时针扭转,DCM患者左心室侧壁基底段、中间段与室间隔基底段扭转达峰时间差可能是形成DCM患者心脏纵向扭转的一个原因.     

Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy.

AIMS: Doxorubicin (Dox) is a potent chemotherapeutic agent associated with severe cardiotoxicity. Erythropoietin (Epo) has recently been shown to exhibit proangiogenic properties related to endothelial progenitor cell (EPC) mobilization. We tested the hypothesis that EPC are compromised in rats with Dox-induced cardiotoxicity and correction of this functional impairment by treatment with Epo could result in attenuation of myocardial dysfunction. METHODS AND RESULTS: Wistar rats were either treated with two different doses of Epo (20U or 200U) or PBS (n = 40 in each group) for four consecutive weeks, followed by Dox administration. In a second study, EPC obtained from healthy rats were transfused intravenously (n = 20/group) prior to induction of Dox cardiomyopathy. EPC from healthy subjects were evaluated for their proliferative and migratory properties in the presence or absence of Dox and Epo pre-treatment. Echocardiography demonstrated an improvement in fractional shortening (FS) in Epo-treated rats. Epo treatment was associated with a reduced mortality in both Epo-treated groups. Circulating EPC numbers were three times higher in Epo-treated compared with non-treated animals. Adhesive properties, migration, and tube formation capacity in matrigel of EPCs from both Epo-treated groups as compared with controls were significantly enhanced. EPC transfer to Dox-treated rats led to functional myocardial improvement equivalent to the protection afforded by treatment with Epo. In EPC obtained from humans, pre-incubation with Epo significantly attenuated the anti-proliferative and anti-migratory effects of treatment with Dox. CONCLUSION: Epo treatment is potentially protective against myocardial dysfunction induced by Dox. These effects are partially mediated by enhancement in the number of EPC and their functional properties.     

扩张型心肌病心肌纤维化血清指标观察

目的 :观察原发性扩张型心肌病 (DCM )患者心肌纤维化血清学指标变化及血浆血管紧张素Ⅱ (AngⅡ )和醛固酮 (ALD)浓度 ,探讨心肌纤维化机制。方法 :采用放射免疫方法测定 35例原发性DCM和 2 4例正常对照者血清中Ⅲ型前胶原 (PCⅢ )、层粘连蛋白 (LN)、透明质酸 (HA)及血浆AngⅡ和ALD含量 ,将AngⅡ、ALD分别与PCⅢ、LN、HA进行相关分析。 结果 :原发性DCM血清PCⅢ、LN、HA及血浆AngⅡ、ALD浓度明显增高 ,AngⅡ、ALD分别与PCⅢ、LN、HA密切相关。结论 :原发性DCM存在不同程度心肌纤维化 ,血清中PCⅢ、LN、HA含量可间接反应心肌纤维化程度 ,AngⅡ、ALD在心肌纤维化过程中起着重要作用。     

Cyclic changes in pulmonary wedge v waves in dilated cardiomyopathy

Right and left cardiac catheterization was performed in a 29-year-oldmale with dilated cardiomyopathy. During the procedure, prominentv waves appeared spontaneously in the pulmonary capillary wedgepressure recording with a simultaneous decrease in left ventricularsystolic pressure. Left ventricular angiography showed moderateto severe mitral regurgitation and an ejection fraction of 22%.The right ventricular endomyocardial biopsy revealed histologicalfindings consistent with dilated cardiomyopathy. Cardiac catheterization was repeated 9 months later, after aperiod of clinical improvement and a reduction in the rightand left ventricular filling pressures was documented. The cyclicswings in the pulmonary capillary wedge pressure and in theleft ventricular systolic pressure were not observed. Left ventriculographyshowed mild mitral regurgitation with an ejection fraction of37%. Right ventricular endomyocardial biopsy documented a reductionin myofibrillar and nuclear hypertrophy. Thus, cyclic changesin pulmonary wedge v waves may be observed in dilated cardiomyopathy.This finding is consistent with cyclic variations in the degreeof mitral regurgitation. Disappearance of this factor seemsto be related to improvement in left ventricular contractility.