Morphological manifestations of heart remodeling in anthracycline-induced dilated cardiomyopathy

The morphogenesis of anthracycline-induced dilated cardiomyopathy was studied after single sublethal dose of doxorubicin. Cardiomyocyte depopulation (up to 27%) and decrease in their regeneratory plastic reactions were the main mechanisms of cardiac failure development after anthracycline (doxorubicin) treatment, determining the type of heart remodeling by the dilatation variant. Cardiomyocyte elimination and atrophy during the development of anthracycline-induced regeneratory plastic cardiac insufficiency were paralleled by hypertrophy of remaining cardiomyocytes and diffuse and small focal sclerosis of the myocardium, which could be regarded as a correlated compensatory reaction of the connective tissue to the decrease in the number of muscle fibers.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 12, pp. 684–689, December, 2004This revised version was published online in April 2005 with a corrected cover date.     

Changes in myocardial collagen content before and after left ventricular assist device application in dilated cardiomyopathy

Background The purposes of this study were to confirm the changes in myocardial collagen level after left ventricular assist device (LVAD) support in dilated cardiomyopathy (DCM), find the relation between these changes and prognosis, and test a practical method to assess the level of myocardial collagen.Methods Left ventricular samples were collected from DCM patients with different prognosis (transplanted group n=8, weaning group n=10) at the time when the LVADs were implanted and again during cardiac transplantation (n=8). The level of neutral salt soluble collagen (NSC) and acid soluble collagen (ASC) was measured by Sircol collagen assay, and that of total collagen and insoluble collagen (ISC) by quantification of hydroxyproline (Hyp). Serum samples were collected from a portion of these patients (transplanted group, n=6; weaning group n=7) at the time the LVADs were implanted, 1 month after implantation and on explantation. Circulating concentration of carboxy-terminal propeptide of type Ⅰ procollagen (PⅠCP), amino-terminal propeptide of type Ⅰ procollagen (PⅠNP), amino-terminal propeptide of type Ⅲ procollagen (PⅢNP) and type Ⅰ collagen telopeptide (ⅠCTP) were measured by the equilibrium type radioimmunoassay. Results Before LVAD implantation the level of NSC and ISC in the weaning group was higher but ASC in the transplanted group was lower than in the controls (P<0.05). After LVAD support, the level of total collagen was higher, but ASC was also lower in the transplanted group than in the controls (P<0.05). In comparison of the pre- and post-LVAD subgroups of the transplanted and weaning groups, all collagen fraction levels before LVAD implantation were lower in the transplanted group than in the weaning group (P<0.05); but this difference disappeared after LVAD support. Comparison of the pre- and post-LVAD subgroups of the transplanted group showed increased level of NSC and total collagen after LVAD support. The changes of serum peptide concentration showed that PⅢNP increased constantly in the transplanted group, but PⅠCP and PⅠNP increased in the weaning group after LVAD implantation. Conclusions The changes in myocardial collagen level as a sign of myocardial interstitial remodeling in DCM are not involved with total collagen but invalved with collagen fractions, and they are related to prognosis. The changes of myocardial collagen content and serum procollagen peptide after LVAD support can be regarded as an expression of the reverse of maladaptive myocardial interstitial remodeling.     

Dynamic Cardiomyoplasty as a Therapeutic Alternative: Current Status

Dynamic cardiomyoplasty was proposed as an alternative surgical treatment for severe cardiomyopathies and has been performed worldwide in more than 1,000 patients. Patients indicated for this procedure are specifically those with dilated or ischemic cardiomyopathies. The ventricular function improvement observed after dynamic cardiomyoplasty derived from the direct action of synchronized skeletal muscle flap contraction and from a girdling effect that helps to reverse chamber remodeling and to decrease ventricular wall stress. Although long-term benefits of this procedure may be limited by skeletal muscle flap ischemic compromise, technological advances incorporated in the new myostimulators will possibly decrease this complication incidence. Clinical improvement has been reported as a consistent finding in cardiomyoplasty follow-up and the overall 5-year survival after this procedure ranges from 39 % to 54 %. On the other hand, the mortality after cardiomyoplasty has been significantly higher for patients in persistent New York Heart Association functional class IV, showing that this procedure needs to be indicated earlier than the heart transplantation. In this regard, only the results of an ongoing randomized trial will potentially define cardiomyoplasty influence on the survival of patients with severe heart failure. In the meantime, however, there are clearly several functional class III patients whose quality of life and exercise capacity have worsened despite the use of maximum medical therapy, justifying dynamic cardiomyoplasty indication.     

Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy: A comparison of123I-MIBG scintigraphic and echocardiographic data

It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and 123I-MIBG scintigraphy. Both of these methods are associated with beta-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patients with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low-dose dobutamine stress echocardiography: and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123 [123I] meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with 123I-MIBG provided quantitative assessment of the heart-to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r = 0.682, p = 0.0146), wall motion after dobutamine stress (r = 0.758, p = 0.0043), the change in wall motion (r = 0.667, p = 0.0178), and with left ventricular diastolic diameter (r = 0.837, p = 0.0007). In addition, the 123I-MIBG washout rate correlated with baseline wall motion (r = 0.608, p = 0.0360), wall motion after dobutamine stress (r = 0.703, p = 0.0107), and with the change in wall motion (r = 0.664, p = 0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure.     

原发性扩张型心肌病96例患儿长期随访

目的 探讨原发性扩张型心肌病(DCM)患儿临床特点、长期预后及其死亡的相关危险因素.方法 对1985年10月-2008年10月南京医科大学附属南京儿童医院收住院的118例DCM患儿进行随访.118例DCM患儿中共96例(81%)获得随访,22例(19%)失访.根据患儿转归不同将96例获得随访的患儿分为死亡组(53例)和存活组(43例).应用SPSS 13.0软件进行统计学分析.结果 DCM患儿1 a、2 a、3 a和5 a生存率分别为65.60%、62.50%、56.25%及44.79%.性别、家族史、心力衰竭史及奔马律在死亡组和存活组间差异均无统计学意义,而农村人口 (死亡组35例 vs存活组18例,P=0.018)、初次发病平均年龄(死亡组M 35.3个月,Q 8.4～99.0个月;存活组M 13.7个月,Q 5.5～42.3个月,P=0.002)及从发病到就诊平均时间(死亡组M 21.0 d,Q 9.5～60.0 d;存活组M 14.0 d,Q 7.0～21.0 d,P=0.043)在二组间差异有统计学意义.ECG示左心室肥厚(死亡组23例 vs存活组30例,P=0.010)可能是预后良好的指标,而心房扩大(死亡组14例 vs存活组2例,P=0.005)及病理性Q波(死亡组7例 vs存活组0例,P=0.022)往往提示预后不良.心脏超声中EF值≤20%(死亡组13例 vs存活组0例,P=0.001)、FS值≤10%(死亡组16例 vs存活组4例,P=0.012)及治疗后EF和(或)FS增长率不明显[死亡组4.14% 和(或) 5.53% vs存活组55.48% 和(或)63.62%,Pa＝0.000]提示预后不佳.初次发病年龄＞5岁患儿病死率显著高于发病年龄≤5岁者(76.92% vs 47.14%,P=0.009).初次发病年龄＞5岁(OR=16.000,95%CI 2.001～127.925,P=0.009)是小儿DCM独立危险因素,左心室肥厚(OR=0.057,95%CI 0.014～0.222,P=0.000)则是独立保护性因素.结论 DCM常预后不良,远期存活率不高,发病年龄＞5岁是小儿DCM的独立危险因素.1000     

Fixed dilated pupils and tacrolimus toxicity in paediatric liver transplant patients

Westrope C, Rowlands H, Morris K, Gupte GL. Fixed dilated pupils and tacrolimus toxicity in paediatric liver transplant patients.
Pediatr Transplantation 2011: 15: E96–E99. © 2010 John Wiley & Sons A/S. Abstract: We report a case series of four children who developed fixed dilated pupils associated with high tacrolimus levels (>30 nanograms/millilitre [ng/mL]) in the immediate post‐operative period following isolated liver or liver and small bowel transplantation.     

免疫球蛋白联合去乙酰毛花苷注射液治疗老年扩张型心肌病的临床研究

目的探讨免疫球蛋白联合去乙酰毛花苷注射液治疗老年扩张型心肌病的临床疗效。方法选取2010年1月—2014年12月榆林市第一医院心血管内科收治的老年扩张型心肌病患者200例,随机分为对照组和治疗组,每组各100例。两组患者均接受利尿剂等常规基础治疗。对照组患者静脉滴注去乙酰毛花苷注射液,0.5 mg/次,2次/d;治疗组在对照组基础上静脉滴注静注人免疫球蛋白,400 mg/d。两组均连续治疗4周。观察两组的临床疗效,同时比较两组治疗前后左心室射血分数(LVEF)、舒张早期血流峰值速度(EPFV)、充盈早期速率/晚期速率(E/A)、舒张晚期血流峰值速度(APFV)、左心室收缩末期容积(LVESV)、左心室质量(LV)、左心室舒张末期容积(LVEDV)、心胸比(CTR)、Ig G抗体的变化情况。结果治疗后,对照组和治疗组的总有效率分别为69.00%、85.00%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者LVEF、E/A、EPFV显著升高,APFV、LVESV、LVEDV、LV、CTR、Ig G抗体均显著降低,同组治疗前后差异具有统计学意义(P0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异具有统计学意义(P0.05)。结论免疫球蛋白联合去乙酰毛花苷注射液治疗老年扩张型心肌病具有较好的临床疗效,可显著改善患者的心功能,降低Ig G抗体水平,具有一定的临床推广应用价值。     

不同免疫剂治疗扩张型心肌病患儿心功能和临床预后评价

目的观察比较泼尼松联用硫唑嘌呤和大剂量静脉用免疫球蛋白(IVIG)对扩张型心肌病(DCM)患儿心功能及预后的影响。方法将DCM患儿20例分为治疗Ⅰ和Ⅱ组,分别在传统抗心衰治疗基础上加泼尼松联用硫唑嘌呤和大剂量IVIG,治疗1个疗程后评价心功能,检测治疗前后左房横径(LA)、左室舒张期内径(LV)、左室射血分数(LVEF)、心脏指数(CI),并计算其治疗前后变化。所有病例随访1年,计算1年存活率。结果治疗Ⅱ组心功能明显优于治疗Ⅰ组(P均<0.05);两组LA、LV、LVEF和CI治疗后较治疗前均有明显改善(P均<0.05);治疗Ⅰ组各参数变化明显低于治疗Ⅱ组(P均<0.05),其1年存活率明显低于治疗组Ⅱ(P<0.05)。结论泼尼松联用硫唑嘌呤和大剂量IVIG均能改善DCM患儿心功能,但IVIG疗效优于泼尼松联用硫唑嘌呤。     

Association between Endothelial Function and Chronotropic Incompetence in Subjects with Chronic Heart Failure Receiving Optimal Medical Therapy

Objective: Impairment of flow‐mediated, endothelium‐dependent vasodilatation (FMD) of the brachial artery identifies peripheral endothelial dysfunction in subjects with chronic congestive heart failure (CHF) and is associated with increased morbidity and mortality. To further elucidate the interaction of peripheral and central mechanisms in the syndrome of CHF, we examined the association between endothelial function and chronotropic incompetence, an emerging prognostic marker in CHF. Methods: Thirty subjects with stable New York Heart Association (NYHA) functional class II–III CHF were studied. A vascular ultrasound study was performed to measure brachial artery FMD. The percentage of age‐adjusted maximal predicted heart rate (MPHR) reached during cardiopulmonary exercise tolerance testing (CPETT) was used to assess the degree of chronotropic competence. All patients received ACE inhibitors and β‐adrenoceptor blockers. Results: Brachial artery FMD averaged 1.3 ± 2.4% and age‐adjusted % MPHR 74.1 ± 11.7%. FMD correlated with % MPHR among all patients (r = 0.60, P = 0.01). FMD and resting heart rate (RHR) did not significantly correlate (r = 0.13, P = 0.55). Conclusions: FMD, a measure of peripheral endothelial dysfunction, and % MPHR, a central determinant of cardiac output, are moderately correlated in heart failure patients receiving optimal medical therapy. Whether a cause‐effect relationship underlies this association remains to be investigated. (Echocardiography 2010;27:294‐299)