Diabetic cardiomyopathy: Pathophysiology,theories and evidence to date

The prevalence of type 2 diabetes(T2D) has increased worldwide and doubled over the last two decades. It features among the top 10 causes of mortality and morbidity in the world. Cardiovascular disease is the leading cause of complications in diabetes and within this, heart failure has been shown to be the leading cause of emergency admissions in the United Kingdom. There are many hypotheses and well-evidenced mechanisms by which diabetic cardiomyopathy as an entity develops. This review aims to give an overview of these mechanisms,with particular emphasis on metabolic inflexibility. T2D is associated with inefficient substrate utilisation, an inability to increase glucose metabolism and dependence on fatty acid oxidation within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction and finally in overt heart failure. The review also gives a concise update on developments within clinical imaging, specifically cardiac magnetic resonance studies to characterise and phenotype early cardiac dysfunction in T2D. A better understanding of the pathophysiology involved provides a platform for targeted therapy in diabetes to prevent the development of early heart failure with preserved ejection fraction.     

Diabetic heart disease: A clinical update

Diabetes mellitus (DM) significantly increases the risk of heart disease, and DM-related healthcare expenditure is predominantly for the management of cardiovascular complications. Diabetic heart disease is a conglomeration of coronary artery disease (CAD), cardiac autonomic neuropathy (CAN), and diabetic cardiomyopathy (DCM). The Framingham study clearly showed a 2 to 4-fold excess risk of CAD in patients with DM. Pathogenic mechanisms, clinical presentation, and management options for DM-associated CAD are somewhat different from CAD among nondiabetics. Higher prevalence at a lower age and more aggressive disease in DM-associated CAD make diabetic individuals more vulnerable to premature death. Although common among diabetic individuals, CAN and DCM are often under-recognised and undiagnosed cardiac complications. Structural and functional alterations in the myocardial innervation related to uncontrolled diabetes result in damage to cardiac autonomic nerves, causing CAN. Similarly, damage to the cardiomyocytes from complex pathophysiological processes of uncontrolled DM results in DCM, a form of cardiomyopathy diagnosed in the absence of other causes for structural heart disease. Though optimal management of DM from early stages of the disease can reduce the risk of diabetic heart disease, it is often impractical in the real world due to many reasons. Therefore, it is imperative for every clinician involved in diabetes care to have a good understanding of the pathophysiology, clinical picture, diagnostic methods, and management of diabetes-related cardiac illness, to reduce morbidity and mortality among patients. This clinical review is to empower the global scientific fraternity with up-to-date knowledge on diabetic heart disease.     

Cardiovascular autonomic neuropathy in diabetes: Pathophysiology,clinical assessment and implications

Cardiovascular autonomic neuropathy (CAN) is a debilitating condition that mainly occurs in long-standing type 2 diabetes patients but can manifest earlier, even before diabetes is diagnosed. CAN is a microvascular complication that results from lesions of the sympathetic and parasympathetic nerve fibers, which innervate the heart and blood vessels and promote alterations in cardiovascular autonomic control. The entire mechanism is still not elucidated, but several aspects of the pathophysiology of CAN have already been described, such as the production of advanced glycation end products, reactive oxygen species, nuclear factor kappa B, and pro-inflammatory cytokines. This microvascular complication is an important risk factor for silent myocardial ischemia, chronic kidney disease, myocardial dysfunction, major cardiovascular events, cardiac arrhythmias, and sudden death. It has also been suggested that, compared to other traditional cardiovascular risk factors, CAN progression may have a greater impact on cardiovascular disease development. However, CAN might be subclinical for several years, and a late diagnosis increases the mortality risk. The duration of the transition period from the subclinical to clinical stage remains unknown, but the progression of CAN is associated with a poor prognosis. Several tests can be used for CAN diagnosis, such as heart rate variability (HRV), cardiovascular autonomic reflex tests, and myocardial scintigraphy. Currently, it has already been described that CAN could be detected even during the subclinical stage through a reduction in HRV, which is a non-invasive test with a lower operating cost. Therefore, considering that diabetes mellitus is a global epidemic and that diabetic neuropathy is the most common chronic complication of diabetes, the early identification and treatment of CAN could be a key point to mitigate the morbidity and mortality associated with this long-lasting condition.     

围产期心肌病诊治分析

目的通过分析围产期心肌病(PPCM)的临床特点,寻找帮助早期诊断的临床征象,并为临床确立治疗方案和选择分娩时机提供依据。方法回顾性分析北京协和医院确诊的27例PPCM患者的临床表现、诊断、治疗及预后。结果PPCM是妊娠最后1个月或产后5个月内发病,不明原因的心脏扩大和心功能衰竭,符合扩张型心肌病的诊断标准。我院分娩的孕产妇中PPCM发病率约为1/1 630(0.061%)。患者表现出心功能不全的症状及体征,超声心动图显示左心室射血分数显著减低,为(35.8±10.0)%,可伴有心电图异常和血清B型脑钠肽升高,还可合并妊娠期高血压等疾病。经积极地抗心力衰竭治疗,心功能多可改善。产前发病者早产率约为77.3%,终止妊娠以剖宫产为主,胎儿可出现胎死宫内、新生儿死亡、重度窒息等。结论 PPCM患者早期临床表现多不典型,超声心动图是重要的诊断依据。经及时正规的药物治疗和终止妊娠,PPCM患者心功能多可改善,孕产妇总体预后相对较好,但胎儿或新生儿不良结局风险高,故建议及时终止妊娠。     

Diabetic foot ulcer: Challenges and future

Diabetic foot ulcers (DFUs) have become one of the important causes of mortality and morbidity in patients with diabetes, and they are also a common cause of hospitalization, which places a heavy burden on patients and society. The prevention and treatment of DFUs requires multidisciplinary management. By controlling various risk factors, such as blood glucose levels, blood pressure, lipid levels and smoking cessation, local management of DFUs should be strengthened, such as debridement, dressing, revascularization, stem cell decompression and oxygen therapy. If necessary, systemic anti-infection treatment should be administered. We reviewed the progress in the clinical practice of treating DFUs in recent years, such as revascularization, wound repair, offloading, stem cell transplantation, and anti-infection treatment. We also summarized and prospectively analyzed some new technologies and measurements used in the treatment of DFUs and noted the future challenges and directions for the development of DFU treatments.     

先天性冠状动脉瘘的临床分析

目的：探讨61例先天性冠状动脉瘘(CAF)的临床特点及治疗方法。方法：1984年至2002年，应用超声心动图、升主动脉及选择性冠状动脉造影检查确诊CAF 61例。其中男34例，女27例；年龄5个月至71岁。其中51例为单纯性CAF，10例伴其他先天性畸形。单支娈管起源于左冠状动脉26例，右冠状动脉29例。结果：8例未进行有创干预治疗。46例行外科手术治疗。治愈44例；死亡2例。均为合并其他先天性畸形者。7例行导管栓堵治疗，6例治愈。1例因导管到位困难停止手术。结论：超声心动图及选择性冠状动脉造影是冠状动脉瘘主要确诊手段。外科手术和经导管栓堵术闭合冠状动脉瘘均安全有效，应在临床症状出现前进行根治性治疗。     

Role of novel biomarkers in diabetic cardiomyopathy

Diabetic cardiomyopathy(DCM) is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and hypertension. As DCM is now recognized as a cause of substantial morbidity and mortality among patients with diabetes mellitus and clinical diagnosis is still inappropriate, various expert groups struggled to identify a suitable biomarker that will help in the recognition and management of DCM, with little success so far. Hence, we thought it important to address the role of biomarkers that have shown potential in either human or animal studies and which could eventually result in mitigating the poor outcomes of DCM. Among the array of biomarkers we thoroughly analyzed, long noncoding ribonucleic acids, soluble form of suppression of tumorigenicity 2 and galectin-3 seem to be most beneficial for DCM detection, as their plasma/serum levels accurately correlate with the early stages of DCM. The combination of relatively inexpensive and accurate speckle tracking echocardiography with some of the highlighted biomarkers may be a promising screening method for newly diagnosed diabetes mellitus type 2 patients. The purpose of the screening test would be to direct affected patients to more specific confirmation tests. This perspective is in concordance with current guidelines that accentuate the importance of an interdisciplinary team-based approach.     

三维超声评价Dor法切除左心室室壁瘤对左心室形态和功能的影响

目的使用三维超声建立一种新的左心室形态定量指标,评价Dor法室壁瘤切除术对左心室形态和功能的影响。方法2003年5月至2004年4月,18例冠心病病人,根据术前二维心脏超声诊断,分为室壁瘤组、左心室扩大组和正常对照组,每组6例。比较3组病人术前、术后心功能和心室三维形态指数(心室锥度,C值)的变化。结果3组均无手术死亡。正常对照组术前、术后的EF、左心室容积、形态没有明显变化。室壁瘤组术后左心室容积明显减少,EF从术前0.43±0.06提高到术后0.54±0.08(P=0.02);左心室三维形态更接近类圆锥体(C值接近于1),舒张心室锥度从术前0.36±0.04提高到术后0.56±0.04(P=0.02),收缩末心室锥度从术前0.42±0.03提高到术后0.60±0.05(P=0.03)。室壁瘤组心室形态改善显著。结论Dor法能有效改善左心室室壁瘤病人的心功能和心室形态。三维超声是进行心室形态定量研究的精确、有效、经济的新手段。     

冠心病心力衰竭病人胸段硬膜外阻滞后心功能变化

目的：观察冠心病心力衰竭（CHF）病人高位胸段硬膜外阻滞（HTEA）前后脂质过氧化物和左心室舒缩功能的变化，方法：选择48例冠心病心力衰竭病人均分为HTEA组（n=24)及常规治疗组（n=24),观察治疗前后心功能，丙二醛（MDA），超氧化物歧化酶（SOD）的变化。结果：治疗后CHF病人心脏舒缩功能的改善；HTEA组明显优于常规治疗组（P＜0．05），MDA含量HTEA组明显低于常规治疗组（P＜0．01），SOD则明显高于常规治疗组（P＜0．05），结论：HTEA治疗CHF病人对心脏舒缩功能的改善明显优于常规法，其增强抵抗自由基的能力是可能的机制之一。     

组织多普勒成像监测冠状动脉旁路移植术患者左心室功能的可行性

目的采用组织多普勒成像(TDI)技术监测冠状动脉旁路移植前、后左心室前壁心肌组织功能的变化,评价TDI术中监测左心室功能的可行性。方法随机连续选择左前降支冠状动脉旁路移植术患者40例,采用TEE探头在胃底左心室短轴切面取左心室前壁中层行TDI采样,记录收缩速度(Vs)、舒张早期速度(Ve)、舒张晚期速度(Va),并计算Ve/Va;采用TEE二维超声行左室室壁运动视觉评分,测量左心室射血分数(EF)、左心室充盈早期血流速度(E)、晚期速度(A)频谱,并计算E/A;通过肺动脉导管记录心输出量(CO)、肺毛细血管楔压(PCWP)和中心静脉压(CVP)。将TDI技术测定的左心室功能参数分别与TEE二维超声和肺动脉导管测定的参数进行直线相关分析。结果所有患者均可获得满意的左心室前壁中层TDI频谱;冠状动脉旁路移植后左心室前壁Vs、Ve、Va较移植前增加(P<0.05),Ve/Va无明显变化(P>0.05);移植后室壁运动视觉评分改善,EF增加(P<0.05),二尖瓣频谱显示A波增加(P<0.05),E波无明显变化,E/A下降(P<0.01);移植后CO及心指数(CI)增加(P<0.01)。直线相关分析显示左室前壁Vs与CO、CI无相关关系,Ve/Va与CVP、PCWP和二尖瓣血流E/A在移植前、后均无相关关系。TDI未提示患者出现新的心肌缺血证据。结论左心室前壁TDI能定量测定冠状动脉旁路移植前、后局部心肌组织功能的变化,但不能反映左心室整体功能的变化。     

Kidney transplantation and cardiomyopathy: Concepts and controversies in clinical decision-making

Increasing comorbidities and an aging population have led to a tremendous increase in the burden of both kidney and cardiac dysfunction. Concomitant cardiomyopathy exposes the patients with kidney disease to further physiological, hemodynamic, and pathologic alterations. Kidney transplantation imposes lesser anesthetic and surgical complexities compared to another solid organ transplant. The surgical decision-making remains an unsettled issue in these conditions. The surgical choices, techniques, and sequences in kidney transplant and cardiac surgery depend on the pathophysiological perturbations and perioperative outcomes. The absence of randomized controlled trials eludes us from suggesting definite management protocol in patients with end-stage kidney disease with cardiomyopathy. Nevertheless, in this review, we extracted data from published literature to understand the pathophysiologic interactions between end-stage renal diseases with cardiomyopathy and also proposed the management algorithm in this challenging scenario. The proposed management algorithm would ensure consensus across all stakeholders involved in decision-making. Our simplistic evidence-based approach would augur future randomized trials and would further ensure refinement in our management approach after the emergence of more definitive evidence.     

同期心脏瓣膜手术与冠状动脉旁路移植术81例

目的总结同期施行心脏瓣膜手术和冠状动脉旁路移植术(CABG)的效果和临床经验。方法2000年1月至2005年12月我科同期施行心脏瓣膜手术/CABG 81例。风湿性心脏瓣膜疾病合并冠状动脉病变37例,冠心病合并心脏瓣膜功能不全44例。冠状动脉造影显示:单支血管病变18例,双支血管病变9例,多支血管病变54例。同期施行心瓣膜置换术和CABG 55例,瓣膜成形术和CABG 26例,其中同期行室壁瘤手术4例。人均冠状动脉远端吻合3.12±1.51个。术后发生低心排血量4例,需主动脉内球囊反搏支持。结果2例因手术后发生低心排血量和多器官功能衰竭死亡。再次开胸止血3例。79例患者取得了良好的临床效果,心脏功能明显改善。手术后随访64例,失访15例,随访时间1~74个月,平均随访14.2个月,随访期间死亡5例,均为非心源性死亡。其余患者生活质量明显改善。结论同期施行心脏瓣膜手术/CABG是有效可行的,近期效果满意。     

肝移植受者术前心脏疾病风险评估的现状及展望

随着肝移植疾病谱和器官分配体系等因素的改变,越来越多伴有心血管合并症的患者进入移植等待名单。手术应激、严重感染、免疫抑制药物不良反应等亦会导致术后心脏并发症发生风险显著增加,影响受者短期及长期生存。因此,术前对受者心脏结构及功能进行全面评估,对改善肝移植预后尤其重要。本文就肝移植围手术期心脏疾病风险增加的主要原因、肝移植受者心脏疾病风险评估的时机和方法进行综述,介绍当前肝移植术前常见心脏疾病的评估手段,以期为进一步降低肝移植术后心脏并发症发生率、提高移植物和受者存活率、改善临床预后结果提供参考。     

Constrictive pericarditis, still a diagnostic challenge: comprehensive review of clinical management

The diagnosis of constrictive pericarditis (CP) continues to be a challenge in the modern era. Understanding the pathophysiology and integrating the results of invasive and non-invasive techniques are important in the differential diagnosis of CP and e.g. restrictive cardiomyopathy. New echocardiographic techniques such as tissue Doppler imaging (TDI) and 2D-speckle tracking, dual-source CT (computed tomographic imaging) and especially tagged cine-MRI (magnetic resonance imaging) with the analysis of phase contrast angiography sequences are promising novel approaches. Pericardiectomy in experienced centers with complete decortication (if technically feasible) is the treatment of choice for CP and it results in symptomatic relief in most patients. However, some patients may not benefit from pericardiectomy and this may be due to myocardial compliance abnormalities, myocardial atrophy after prolonged constriction, residual constriction or other myocardial processes. An important predictor of long-term outcome after pericardiectomy is the etiology of the pericardial disease. The overall mortality in the current literature is nearly 5–6%. Survival with post-surgical CP is worse than with idiopathic CP, but significantly better than with post-radiation CP.     

Diabetic foot disease:From the evaluation of the “foot at risk” to the novel diabetic ulcer treatment modalities

The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy(DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk foot are essential for the prevention of foot ulceration and amputation. Proper assessment of the diabetic foot ulceration and appropriate management ensure better prognosis. Management is based on revascularization procedures, wound debridement, treatment of infection and ulcer offloading. Management and type of dressing applied are tailored according to the type of wound and the foot condition. The scope of this review paper is to describe the diabetic foot syndrome starting from the evaluation of the foot at risk for ulceration, up to the new treatment modalities.     

Impact of mitral insufficiency on reoperative coronary artery surgery in ischemic cardiomyopathy patients

Objective: To determine the impact of mitral insufficiency on survival after reoperative coronary artery bypass grafting (CABG) in ischemic cardiomyopathy patients. Methods: We retrospectively studied 891 (Initial 708, Redo 183) consecutive CABG patients (1993–2002) with ejection fraction (EF) 35% or less. Patient characteristics: mean age=67.0±10.5 yrs, men=77.1%, EF=26.4±7.4%, mean CCS=3.47±0.73, mean NYHA=3.50±0.68. There were 180 (Initial 141, Redo 39) patients with 3/4+mitral regurgitation (MR). Late survival statistics of cohorts were compiled using National Death Index. Results: At a mean follow-up period of 3 years, reoperative CABG with MR (Redo/MR+) survival was 41.7±9.2% (n=39), which was worse than reoperative CABG without MR (Redo/MR−) survival of 71.8±4.1% (n=144, P=0.0003), initial CABG with MR (Initial/MR+) survival of 68.5±4.2% (n=141, P=0.014) and initial CABG without MR (Initial/MR−) survival of 76.2±2.0% (n=567, P<0.0001). By multivariate analysis, congestive heart failure (P=0.029), 3/4+MR (P=0.044) were independent predictors of Redo late mortality. In contrast, renal failure on dialysis, stroke, no angina, age >65 yrs, absence of hypercholesterolemia, EF<26% but not 3/4+MR were independent predictors of Initial late mortality. In subset analysis, adverse impact of 3/4+MR on late survival was greatest in Redo with EF<26%. The 3- and 5-yr late survival were only 44.4 and 26.8% (P=0.041). Concomitant mitral valve repair (MVrep) was performed in 100 (Initial 75, Redo 25) patients. MVrep in Initial/MR+patients achieved similar late survival as Initial/MR− patients. MVrep did not produce the same late survival benefit in Redo/MR+ patients. Conclusions: (1) Mitral insufficiency has a greater survival impact on redo than initial CABG patients with ischemic cardiomyopathy. (2) Mitral insufficiency and congestive heart failure are the primary independent predictors of late survival following redo CABG. (3) Mitral repair has less neutralizing effect on late survival in redo than initial CABG patients.     

The Dor procedure for left ventricular reconstruction. Ten-year clinical experience

Objective: Surgical ventricular restoration by means of the Dor procedure is a surgical option in patients with coronary artery disease, postinfarction left ventricular aneurysm or ischemic dilated cardiomyopathy with or without ventricular tachycardia. The aim of this study was to evaluate the 10-year clinical experience of this procedure in our institution. Methods: From May 1994 to June 2004, surgical ventricular restoration was performed in 101 patients (77 males), mean age 63.8 (35–80) years. All patients presented with angina and/or heart failure and/or ventricular tachycardia. Postinfarction left ventricular aneurysm was present in 97 patients and ischemic dilated cardiomyopathy with a large akinetic left ventricle in 4. The preoperative left ventricular ejection fraction was 27±10 (7–50) %. Multi-vessel disease was present in 80 patients. Ventricular tachycardia was diagnosed in 53 patients (spontaneous VT in 25). Mitral regurgitation more than grade 2 was found in 13 patients. The mean Euroscore was 7.1±2.9 (3–17). Results: All patients underwent the Dor procedure, which in 53 patients included a non-guided endocardectomy and cryoablation for treatment of ventricular tachycardia. Coronary artery bypass grafting was performed in 99 patients and a mitral valve procedure was performed in 29. Intra-aortic balloon pumping was used postoperatively in 14 cases and 24 patients needed inotropic support for more than 24 h. Mean time on the ventilator was 16±25 (3–168) hours and mean stay in the intensive care unit was 2.1±2.2 (0–13) days. Postoperative stroke occurred in 7 patients. Early mortality was 8/101 (7.9%). Mean follow-up in operative survivors was 4.4±2.8 (0.1–10.4) years. Actuarial survival at 1, 3 and 5 years was 88, 79 and 65%. Conclusions: The Dor procedure is a reproducible surgical option for treatment of postinfarction left ventricular aneurysm. Early and long-term results are good in terms of survival.