Simvastatin reduces wasting and improves cardiac function as well as outcome in experimental cancer cachexia

Background

Chronic inflammation is common in cancer cachexia (CC) and directly involved in the atrophy seen in this condition. Recently, several groups have described a form of cardiomyopathy in CC animal models. Hence, we investigated the effect of simvastatin with its known anti-inflammatory and cardioprotective effects in a rat model of CC.

Methods

Juvenile Wister Han rats (weight approx. 200 g) were inoculated with Yoshida AH-130 hepatoma cells and treated once daily with 0.1, 1, 10 or 20 mg/kg/d simvastatin or placebo for 14 days. Body weight and body composition (NMR) were assessed at baseline and at the end of the study. Cardiac function was analysed by echocardiography at baseline and day 11.

Results

Tumour-bearing, placebo-treated rats lost 47.9 ± 3.8 g of their initial body weight. Treatment with 0.1, 1, 10 or 20 mg/kg/d simvastatin significantly reduced wasting by 39.6%, 47.6%, 28.5% and 35.4%, respectively (all p < 0.05 vs. placebo). This was mainly due to reduced atrophy of lean mass, i.e. muscle mass. Cardiac function was significantly improved, e.g. cardiac output (untreated sham: 78.9 mL/min) was severely impaired in tumour-bearing rats (42.4 mL/min) and improved by 1, 10 or 20 mg/kg/d simvastatin (62.2, 59.0 and 57.0 mL/min, respectively, all p < 0.05 vs. placebo). Most importantly, 10 or 20 mg/kg/d simvastatin reduced mortality (HR:0.16, 95%CI:0.04–0.76, p = 0.021 and HR:0.16, 95%CI:0.03–0.72, p = 0.017 vs placebo, respectively).

Conclusion

Simvastatin attenuated loss of body weight as well as muscle mass and improved cardiac function leading to improved survival in this CC model. Simvastatin may be beneficial in a clinical setting to treat CC.     

The small molecule ACM-001 improves cardiac function in a rat model of severe cancer cachexia

Aims

Cachexia, a common manifestation of malignant cancer, is not only associated with weight loss, but also with severe cardiac atrophy and impaired cardiac function. Here, we investigated the effects of ACM-001 (0.3 or 3 mg/kg/day) in comparison to carvedilol (3 or 30 mg/kg/day), metropolol (50 or 100 mg/kg/day), nebivolol (1 or 10 mg/kg/day) and tertatolol (0.5 or 5 mg/kg/day) on cardiac mass and function in a rat cancer cachexia model.

Methods and results

Young male Wistar Han rats were inoculated i.p. with 10⁸ Yoshida hepatoma AH-130 cells and treated once daily with verum or placebo by gavage. Cardiac function (echocardiography), body weight and body composition (nuclear magnetic resonance scans) were assessed. The hearts of animals were euthanized on day 11 (placebo and 3 mg/kg/day ACM-001) were used for signalling studies. Beta-blockers had no effect on tumour burden. ACM-001 reduced body weight loss (placebo: −34 ± 2.4 g vs. 3 mg/kg/day ACM-001: −14.8 ± 8.4 g, p = 0.033). Lean mass wasting was attenuated (placebo: −16.5 ± 2.34 g vs. 3 mg/kg/day ACM-001: −2.4 ± 6.7 g, p = 0.037), while fat loss was similar (p = 0.4) on day 11. Placebo animals lost left ventricular mass (−101 ± 14 mg), which was prevented only by 3 mg/kg/day ACM-001 (7 ± 25 mg, p < 0.01 vs. placebo). ACM-001 improved the ejection fraction (EF) (ΔEF: placebo: −24.3 ± 2.6 vs. 3 mg/kg/day ACM-001: 0.1 ± 2.9, p < 0.001). Cardiac output was 50% lower in the placebo group (−41 ± 4 ml/min) compared to baseline, while 3 mg/kg/day ACM-001 preserved cardiac output (−5 ± 8 ml/min, p < 0.01). The molecular mechanisms involved inhibition of protein degradation and activation of protein synthesis pathways.

Conclusion

This study shows that 3 mg/kg/day ACM-001 restores the anabolic/catabolic balance in cardiac muscle leading to improved function. Moreover, not all beta-blockers have similar effects.     

The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy

Background

Cachexia is a common complication of cancer and may be responsible for 22% of all cancer-related deaths. The exact cause of death in cancer cachexia patients is unknown. Recently, atrophy of the heart has been described in cancer cachexia animal models, which resulted in impaired cardiac function and is likely to contribute to mortality. In cancer patients hyperuricaemia independent of tumour lysis syndrome is often associated with a worse prognosis. Xanthine oxidase (XO) metabolizes purines to uric acid and its inhibition has been shown to improve clinical outcome in patients with chronic heart failure.

Methods

The rat Yoshida AH-130 hepatoma cancer cachexia model was used in this study. Rats were treated with 4 or 40 mg/kg/d oxypurinol or placebo starting one day after tumour-inoculation for maximal 15 days. Cardiac function was analyzed by echocardiography on day 11.

Results

Here we show that inhibition of XO by oxypurinol significantly reduces wasting of the heart and preserves cardiac function. LVEF was higher in tumour-bearing rats treated with 4 mg/kg/d (61 ± 4%) or 40 mg/kg/d (64 ± 5%) oxypurinol vs placebo (51 ± 3%, both p < 0.05). Fractional shortening was improved by 4 mg/kg/d (43 ± 3%) oxypurinol vs placebo (30 ± 2, p < 0.05), while 40 mg/kg/d oxypurinol (41 ± 5%) did not reach statistical significance. Cardiac output was increased in the 4 mg/kg/d dose only (71 ± 11 mL/min vs placebo 38 ± 4 mL/min, p < 0.01).

Conclusion

Inhibition of XO with oxypurinol has beneficial effects on cardiac mass and function in a rat model of severe cancer cachexia, suggesting that XO might be a viable drug target in cancer cachexia.     

Cardiac cachexia is associated with right ventricular failure and liver dysfunction

Background

The mechanisms involved in cardiac cachexia remain poorly understood. We examined the association of right ventricular (RV) and hepatic dysfunction with cardiac cachexia.

Methods

We prospectively enrolled 118 patients with left ventricular ejection fraction (LVEF) ≤ 40%, which were subgrouped as follows: New York Heart Association (NYHA) class II (n = 59), NYHA class III without cachexia (n = 41) and NYHA class III with cachexia (n = 18). All patients underwent blood collection, echocardiography and exercise testing.

Results

Reduced systolic RV function (tricuspid annular plane systolic excursion [TAPSE] ≤ 15 mm), was present in 80% of cachectic patients. When comparing NYHA class II patients vs. non-cachectic and cachectic NYHA class III patients we found a stepwise decrease in systolic RV function (TAPSE 19 [16–23] vs. 16 [13–19] vs. 14 [9–15] mm, respectively; p < 0.001) and an increase in right atrial pressure (RAP; > 10 mm Hg: 6.8 vs. 27.5 vs. 75.0%, respectively; p < 0.001), indicating a higher degree of congestive right HF in cardiac cachexia. Systolic and diastolic function of the left ventricle did not differ between non-cachectic and cachectic patients in NYHA class III. Serum alkaline phosphatase and direct bilirubin correlated with TAPSE and RAP, and were highest in cachectic patients (all p ≤ 0.002), suggesting cholestatic dysfunction due to liver congestion. In multivariable regression analysis, RV dysfunction, cholestatic liver parameters and albumin were independently associated with the presence of cardiac cachexia.

Conclusion

Patients with cardiac cachexia display a more pronounced degree of right HF, cholestatic liver dysfunction and hypoalbuminemia compared to non-cachectic patients of similar LVEF and NYHA class.     

Improvement by eicosanoids in cancer cachexia induced by LLC-IL6 transplantation

Cachexia frequently occurs in the late stages of cancer, and is difficult to manage. We previously reported that interleukin-6 (IL-6) cDNA transfection into Lewis lung carcinoma (LLC-IL6) induced cachexia-like symptoms in C57BL/6 mice. This was thought to be a useful experimental model of cancer cachexia. We have examined the effects of two eicosanoids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in order to evaluate whether they could relieve cachexia. LLC-IL6-bearing animals were divided into three treatment groups receiving DHA, EPA or water as the control; 80-l samples of these compounds (purity>95%) were administered orally by catheter daily starting 7 days after tumor transplantation. Tumor growth curves were similar in the three groups. There were no differences in water or food intake in the three groups. However, body weight, a marker of cachexia, was significantly higher in treated mice than in the control group. Sixteen days after tumor transplantation, the mean body weight was 17.45 g (P<0.05), 17.2 g and 16.41 g in the groups receiving DHA, EPA and water respectively. The eicosanoids did not affect serum levels of IL-6. Ubiquitination of muscle protein, a marker of proteolysis coupled to cachexia, was compared in LLC-IL6-and LLC-transplanted mice. The eicosanoids prevented the ubiquitination of approximately 180 kDa protein. These results suggest that eicosanoids may prevent the cachexia mediated by IL-6.Abbreviations DHA docosahexaenoic acid - EPA eicosapentaenoic acid - LLC Lewis lung carcinoma - IL interleukin     

Mitochondrial function in canine experimental cardiac hypertrophy

Concentric left ventricular hypertrophy was produced in puppies by coarctation banding of the aorta at age 7 weeks. Hemodynamic, morphologic and biochemical studies were carried out 18 months after the operation. Systolic blood pressure proximal to the aortic constriction was 216 +/- 16 mmHg in experimental dogs compared with 115 +/- 5 mmHg in littermate control dogs. Ejection fraction of control and experimental dogs were 59 +/- 4 and 64 +/- 7, respectively. The left ventricular end-diastolic pressure was 6.0 +/- 0.4 in control and 8.4 +/- 1.1 in experimental dogs. There was no sign of overt heart failure in the experimental dogs. Anatomical analysis of different regions of the heart indicated that LV mass in the experimental dogs was increased by about 60%. Ultrastructure of mitochondria in situ, as observed under electron microscope, was normal both in control and hypertrophic hearts. Mitochondria isolated from epicardial and endocardial regions of the stable hypertrophic hearts showed normal rates of respiration, phosphorylation, citrate synthase, and cytochrome c oxidase activities compared to those isolated from hearts of littermate control dogs. It was, therefore, concluded that mitochondrial function is adequately preserved to meet the increased demand for energy in this model of stable cardiac hypertrophy of long duration.     

高表达microRNA-22改善小鼠心肌梗死后心功能

目的观察高表达microRNA-22对小鼠心肌梗死后心功能的保护作用及机制。方法构建小鼠心肌梗死模型,用携带microRNA-22的腺病毒载体转染至心肌梗死周围区域,观察高表达microRNA-22对小鼠心肌梗死后心功能的保护作用。采用超声心动图检测心功能,力竭游泳检测运动能力,HE及Masson染色检测心肌微结构及纤维化,Western blot检测PTEN蛋白表达情况。结果高表达microRNA-22组小鼠左心室射血分数(LVEF)(49.38%±2.51%比42.29%±2.74%,P0.05)及短轴缩短率(FS)(24.24%±0.64%比22.59%±0.73%,P0.05)较空载腺病毒组升高,心脏收缩功能维持较好;高表达microRNA-22组力竭运动时间较空载腺病毒组延长(8.13±1.01min比7.02±1.32 min,P0.05),小鼠整体运动能力改善;高表达microRNA-22组小鼠HE染色示心肌结构维持较好,Masson染色示心肌纤维化程度较轻;高表达microRNA-22组心肌梗死周围区域内microRNA-22表达增加(6.66±2.01比1.22±0.07,P0.05),PTEN蛋白表达下降(0.63±0.19比2.23±0.44,P0.05)。结论小鼠心肌梗死后在体高表达microRNA-22改善心脏收缩功能及运动能力,改善心肌微结构,减轻心肌纤维化。     

Low-dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit

BACKGROUND: Erythropoietin (EPO) may improve cardiac function and induce neovascularisation in experimental models of chronic heart failure (CHF). However, the increased haematocrit associated with EPO treatment might exert concomitant deleterious effects. AIM: To investigate the haematocrit independent effects of EPO on cardiac function. METHODS AND RESULTS: Rats underwent permanent coronary artery ligation to induce myocardial infarction (MI) or sham surgery. Three weeks after MI, rats were randomly allocated to treatment with vehicle (MI) or the long-acting EPO analogue darbepoetin alfa administered in a high (40 microg/kg/3 weeks, MI-EPO-high) or a low-dose (0.4 microg/kg/3 weeks, MI-EPO-low). After 9 weeks, haemodynamic parameters, myocardial histology and Myosin Heavy Chain (MHC) isoforms were determined. High-dose EPO resulted in a significant increase in haematocrit (p<0.01) while low-dose EPO had no effect on haematocrit levels. EPO significantly improved cardiac function in both EPO groups, reflected by increased left ventricular (LV)-developed pressure and improved contractility (dP/dt(max)) and relaxation (dP/dt(min)) indices of the LV at 9-weeks (all p<0.05 compared to MI). The improved cardiac function was associated with increased capillary growth (38% in MI-EPO-high (p<0.01) and 27% in MI-EPO-low (p<0.05)) and an attenuated switch to slow beta-MHC isoforms in both EPO groups. CONCLUSIONS: EPO improves cardiac function and induces neovascularisation at a dose that does not increase haematocrit, thereby circumventing the possible deleterious effects of increased erythropoiesis.     

米氮平早期干预对轻度胰腺癌恶液质模型进食和营养状况的影响

目的:探讨抗抑郁药米氮平早期干预对轻度胰腺癌恶液质模型进食量和营养状况的影响.方法:21只胰腺癌裸鼠皮下移植瘤模型随机分为对照组(A组)、米氮平早期干预组(B组)、米氮平后期治疗组(C组),每组7只.B、C组分别在术后第1天和第10天开始以米氮平10mg/(kg.d),灌胃,术后第10、13、16天,3组动物分别腹腔注射吉西他滨(50mg/kg).术后第28天处死裸鼠,比较3组动物体质量、进食量、肿瘤体积、皮下脂肪和臂围的变化.结果:3组胰腺癌移植瘤体积、皮下脂肪和臂围无明显差异(P>0.05).第4周B组进食量显著高于A组和C组(P<0.05);第25天B组体质量(18.05g±0.68g)显著高于A组(17.24g±0.53g,P<0.05),稍高于C组(17.65g±0.60g,P>0.05).结论:米氮平早期干预能显著改善轻度胰腺癌相关恶液质模型的进食量,并能在一定程度上延缓恶液质进程.     

实验性肺炎大鼠肌钙蛋白T的变化及其与心脏收缩功能的关系

目的探讨实验性肺炎大鼠血清肌钙蛋白T(cTnT)的变化及其与心脏收缩功能的关系,以明确肺炎是否可引起心肌受损,以及发生心肌受损的机理。方法建立金黄色葡萄球菌肺炎大鼠模型后第5天行经胸超声心动图检查。测量指标:左室舒张末内径(LVDD)、左室收缩末内径(LVSD)、主动脉血流峰值流速(PFVA)、主动脉血流速度积分(Viao)、肺动脉血流峰值流速(PFVP)、肺动脉血流速度积分(Vipa),并计算左室射血分数(LVEF)、左室短轴缩短率(LVFS)。采用酶联免疫吸附法检测大鼠血清cTnT的水平,并分析cTnT与心脏收缩功能的关系。结果肺炎组大鼠与对照组比较,PFVA、PFVP、Viao、Vipa、LVEF、LVFS显著减少(P均<0.01)。肺炎组大鼠血清cTnT水平显著高于对照组,且与LVEF、LVFS呈负相关(P均<0.05)。结论严重金黄色葡萄球菌肺炎可引起心力衰竭,其发生机理与心肌损害和肺动脉高压有关。血清cTnT可作为诊断心肌受损的生化指标。     

对运动性和DOCA高盐引起的大鼠心脏肥大心脏功能的评价

目的通过建立运动引起的生理性心脏肥大和DOCA高盐引起的病理性心脏肥大大鼠模型，比较评价两种心脏肥大时心脏功能情况。方法采用小动物跑台跑步训练方法和单侧肾脏切除基础上皮下注射醋酸脱氧皮质酮（DOCA）加以高盐饲养方法，分别建立生理性和病理性心脏肥大大鼠模型，应用超声心动图、血流动力学检测、心脏称量等多种方法评价心脏结构和功能情况。结果运动12周后和注射DOCA4周后，大鼠心脏重量均明显大于对照组。DOCA组4周时左心室后壁明显增厚，并且心脏组织胶原表达量明显增加，但对照组和运动组没有变化。和对照组比较，运动6周后心输出量明显增加，12周时更为明显，但DOCA组4周时尽管心脏肥大显著，但心输出量却明显降低。结论跑步训练方法和单侧肾脏切除皮下注射DOCA加以高盐饲养方法成功建立了生理性和病理性心脏肥大大鼠模型，通过超声心动图和血流动力学等检测比较评价两种肥大模型心脏结构和功能变化情况，运动12周后和注射DOCA4周后可产生明显的心脏肥大，前者心脏功能增强，而后者降低。     

肥胖与心脏结构及功能的改变

肥胖者心血管疾病风险增加.研究发现肥胖引起的心脏结构及功能的改变,主要表现为心室重构和心室肥厚,以及心室舒张和收缩功能障碍,这些结构及功能异常严重时可引起心脏衰竭.而肥胖者心脏结构和功能的改变受到多种因素影响,包括血流动力学异常、代谢紊乱、炎性反应、线粒体功能障碍和氧化应激以及神经体液因素.多数研究都发现,减轻体重尤其是减重手术能够逆转肥胖引起的心脏结构和功能改变.     

Circulating Ghrelin in Patients with Gastric or Colorectal Cancer

The purpose of this study was to investigate the pathophysiologic change of ghrelin in gastric and colorectal cancer patients, especially in those with cachexia. Fifty-eight gastric cancer patients, 20 colorectal cancer patients, and 24 healthy control individuals were included in this study. Thirty-one patients were defined as cachectic, based on the percentage of weight loss versus the previous normal weight. The remaining 47 patients were defined as noncachectic. Peripheral hormones, including ghrelin, insulin, leptin, growth hormone, glucagon, and cortisol, and body composition parameters were measured. Plasma ghrelin levels did not increase significantly in cachectic gastric (p=0.352) or colorectal (p=0.871) cancer patients as compared with controls and were not correlated with nutrition status and other hormones. The location of gastric cancer (proximal vs. distal) had no influence on ghrelin levels (p=0.966). These findings suggest that gastric and colorectal cancers may have their special effects on the production of ghrelin. Gastric or colorectal cancer cachexia may be partly due to the lack of increase in ghrelin, which makes exogenous ghrelin therapy feasible in this setting.     

经冠状动脉注射骨髓单个核细胞影响心肌细胞凋亡的实验研究

目的观察经冠状动脉注射方式移植骨髓单个核细胞对心脏功能的改善和心肌细胞凋亡的影响。方法结扎小型猪冠状动脉制备心肌梗死模型，然后经冠状动脉注射骨髓单个核细胞，术后3周用超声心动图以及左心室造影检测心功能．核素心肌显像观察心肌灌注，冠状动脉造影观察侧支循环形成．用TUNEL检测心肌细胞凋亡。结果把骨髓单个核细胞通过冠状动脉注射到猪心肌梗死模型，显示左心室dp／dtmax较对照组增高，心肌灌注显著改善。冠状动脉有侧支循环形成，缺血心肌细胞；较对照组减少了53．6％结论骨髓单个核细胞心肌内移植可改善心脏收缩功能，可能与移植细胞抑制心肌细胞凋亡有关。     

心音图运动试验量化心功能分级的研究

目的:探讨心音图运动试验(PCGET)评估心肌收缩力及心力储备的价值。方法:应用PCGET,把运动后第1心音(s1)幅值与心率的积对安静时S1幅值与心率的积的倍数与6分钟步行距离系数的积,定义为心脏储备指数(CRI)。370位志愿者进行了PCGET,分析不同CRI受试者在纽约心脏病学会心功能(NYHA)分级上的分布。结果:健康和NYHA Ⅰ级的CRI分布于CRI图的高侧;NYHAⅡ、Ⅲ、Ⅳ级的心血管病病人的CRI分布于CRI图的低侧,并且有较好的相关性。CRI、用运动前、后s1幅值计算的心力储备指数(CCRI)与NYHA分级的符合率分别为70.59%与41.76%,二者有显著差异(P<0.005)。结论:CRI可作为心功能分级的客观量化指标之一;且PCGET无创、简便、代价低。     

Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure.

BACKGROUND: Chronic heart failure is one of a number of disorders associated with the development of a wasting syndrome. The precise mechanisms of this remain unknown, but previous studies have suggested a role for immune and neurohormonal factors. METHODS: We aimed to investigate in detail the differences in body composition (dual X-ray absorptiometry) and the relationship to candidate biochemical factors of the immune, neurohormonal and metabolic systems in 15 healthy controls, 36 stable non-cachectic and 18 cachectic patients with chronic heart failure. RESULTS: Non-cachectic patients showed reduced leg lean tissue (-9.1%, P<0.01) compared to controls. Cachectic patients had significantly reduced lean (-21.0% vs controls, -19.9% vs non-cachectics), fat (-33.0% vs controls, -37. 0% vs non-cachectics) and bone tissue (-17.5% vs controls, -15.9% vs non-cachectics) (all P<0.0001). Cachectic patients showed a significantly increased cortisol/dehydroepiandrosterone ratio (+203% vs controls, P<0.0001; +89% vs non-cachectics, P=0.0011) and increased cytokine levels (TNF-alpha, soluble TNF-receptor 1, interleukin-6). The levels of catabolic hormones and cytokines correlated significantly with reduced muscle and fat tissue content and reduced bone mass. CONCLUSION: Peripheral loss of muscle tissue is a general finding in chronic heart failure. The wasting in cardiac cachexia affects all tissue compartments and is significantly related to neurohormonal and immunological abnormalities.     

Chronic metformin reduces systemic and local inflammatory proteins and improves hypertension-related cardiac autonomic dysfunction

Background and aimsMetformin has been known to promote cardiovascular benefits in humans and animal models, even in non-diabetic subjects. However, its chronic effects on hypertension-related autonomic dysfunction remain poorly understood. Therefore, we evaluate the cardiac autonomic effects of chronic metformin in hypertensive rats.Methods and resultsTwelve-week-old male SHR and Wistar rats were separated into 3 groups: WN (Wistar normotensive); SC (SHR hypertensive control); and SM (SHR: Metformin 300 mg/kg/day for 30 days). Spontaneous and induced (by phenylephrine and sodium nitroprusside) baroreflexes were analysed in catheterised rats. Next, cardiac autonomic tone was evaluated through heart rate shift by atropine (parasympathetic) or atenolol (sympathetic). Plasma TNFα was assessed by ELISA. Western blot analyses of inflammatory, oxidant and antioxidant proteins were performed. Cardiac parasympathetic tone and baroreflex function were lower in SC than in WN, whereas cardiac sympathetic tone was higher. Metformin treatment in non-diabetic hypertensive rats reduced the resting heart rate, attenuated the cardiac sympathetic tone and improved baroreflex (especially in the offsetting of rising BP), while blood pressure and glycaemia remained unchanged. Cardiac sympathetic tone correlated negatively with spontaneous baroreflex. Metformin reduced plasma TNFα levels and decreased tissue expression of COX2 and NOX2 (which were positively correlated), without affecting SOD1 and SOD2.ConclusionChronic metformin presented anti-inflammatory and antioxidant effects and, independently of alterations in glycaemia, it improved cardiac autonomic parameters that are impaired in hypertension, being related to end-organ damage and mortality. These findings open up perspectives for future innovative uses of metformin in cardiovascular diseases, especially in hypertension.     

心脏再同步化治疗后心脏结构和功能改变的临床分析

目的：比较心脏再同步化治疗（CRT）后心脏结构和功能的变化,以评估CRT植入对EF降低的慢性心力衰竭（HFrEF）患者的疗效。方法：纳入2017年1月1日至2017年12月31于陆军军医大学第二附属医院心血管内科就诊的HFrEF患者,患者有行CRT指征且同意行CRT,并无CRT植入的相关禁忌症,入院后择期行CRT植入术。患者分别于术前、术后3月、6月行心脏超声检测。测定舒张期心脏各腔室大小,左室射血分数（LVEF）,左室短轴缩短率(FS),每搏输出量（SV）。二尖瓣反流、三尖瓣反流、反流压差等参照指南推荐进行,并比较不同时间点上述各参数的变化。结果：87例患者符合纳入标准,其中15例患者符合排除标准,72例患者行CRT植入术,68例成功完成CRT,纳入本组研究。CRT术后心脏各腔室大小较术前均显著下降（P < 0.05）,术后EF、FS、SV较术前均显著增加（P < 0.05）,术后二尖瓣返流程度、三尖瓣反流程度及三尖瓣反流压差较术前均显著降低（P < 0.05）。结论：CRT可显著改善伴有心脏收缩不同步的HFrEF患者的心脏结构和功能。