Implantation of the Syncardia Total Artificial Heart

With advances in technology, the use of mechanical circulatory support devices for end stage heart failure has rapidly increased. The vast majority of such patients are generally well served by left ventricular assist devices (LVADs). However, a subset of patients with late stage biventricular failure or other significant anatomic lesions are not adequately treated by isolated left ventricular mechanical support. Examples of concomitant cardiac pathology that may be better treated by resection and TAH replacement includes: post infarction ventricular septal defect, aortic root aneurysm / dissection, cardiac allograft failure, massive ventricular thrombus, refractory malignant arrhythmias (independent of filling pressures), hypertrophic / restrictive cardiomyopathy, and complex congenital heart disease. Patients often present with cardiogenic shock and multi system organ dysfunction. Excision of both ventricles and orthotopic replacement with a total artificial heart (TAH) is an effective, albeit extreme, therapy for rapid restoration of blood flow and resuscitation. Perioperative management is focused on end organ resuscitation and physical rehabilitation. In addition to the usual concerns of infection, bleeding, and thromboembolism common to all mechanically supported patients, TAH patients face unique risks with regard to renal failure and anemia. Supplementation of the abrupt decrease in brain natriuretic peptide following ventriculectomy appears to have protective renal effects. Anemia following TAH implantation can be profound and persistent. Nonetheless, the anemia is generally well tolerated and transfusion are limited to avoid HLA sensitization. Until recently, TAH patients were confined as inpatients tethered to a 500 lb pneumatic console driver. Recent introduction of a backpack sized portable driver (currently under clinical trial) has enabled patients to be discharged home and even return to work. Despite the profound presentation of these sick patients, there is a 79-87% success in bridge to transplantation.     

Severe left ventricular systolic dysfunction after permanent pacemaker implantation: Should we pause before upgrading to biventricular pacing?

Left ventricular (LV) systolic dysfunction leading to heart failure (HF) is known to occur after permanent pacemaker implantation (PPI) in a subset of patients. They are often treated by upgradation of the pacemaker to cardiac resynchronisation therapy (CRT). We report a case of progressive LV dysfunction and HF after PPI. Cardiac ¹⁸FDG-PET-CT scan revealed abnormal myocardial FDG uptake suggestive of cardiac sarcoidosis (CS). Biopsy from FDG avid lymph node demonstrated non-caseating granuloma. Therapy with steroids resulted in resolution of HF symptoms accompanied by a significant improvement in LV function.     

Elevation of IGF-2 receptor and the possible underlying implications in end-stage heart failure patients before and after heart transplantation

Up-regulation of insulin-like growth factor 2 receptor (IGF-2R) involved in angiotensin II-induced cell apoptosis in cardiomyoblasts, and correlated with cardiomyocyte apoptosis in hypertensive rat hearts. Here, we detected IGF-2R levels and explored the possible underlying implications in end-stage heart failure (HF) patients before and after heart transplantation. Western blot and immunohistochemistry were used to measure cardiac IGF-2R levels. ELISA was used to detect serum IGF-2R and CD8 levels. Labelling of DNA strand breaks and dihydroethidium detection were used to determine cellular apoptosis and reactive oxygen species, respectively. Cardiac IGF-2R levels increased in end-stage HF patients (n = 11) compared with non-failing control subjects. Leu27-IGF-2, an IGF-2 analogue to activate specially the IGF-2R, could induce apoptosis and reactive oxygen species production in neonatal rat ventricular myocytes. The serum IGF-2R levels were significantly higher in HF patients than those in non-failing control subjects. An unexpected observation is that the serum IGF-2R levels further increased after heart transplantation, peaked at the first month, and gradually reduced close to the levels before heart transplantation at the 6th months after heart transplantation. Serum CD8, a marker of acute rejection, had no change after heart transplantation, but IGF-2R and Granzyme B, as a ligand for the IGF-2R and a marker for CD8 T lymphocyte activation, coexisted in the transplanted hearts. Our preliminary studies suggest that elevation of IGF-2R may participate in pathological process of end-stage HF and involved in the acute cellular rejection after heart transplantation.     

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) IV: Circulating ACE2 as a Biomarker of Systolic Dysfunction in Human Hypertension and Heart Failure

Background

Growing evidence exists for soluble Angiotensin Converting Enzyme-2 (sACE2) as a biomarker in definitive heart failure (HF), but there is little information about changes in sACE2 activity in hypertension with imminent heart failure and in reverse remodeling.

Methods, Findings

Patients with systolic HF (NYHAII-IV, enrolled for cardiac resynchronisation therapy, CRT, n = 100) were compared to hypertensive patients (n = 239) and to a healthy cohort (n = 45) with preserved ejection fraction (EF>50%) in a single center prospective clinical study. The status of the heart failure patients were checked before and after CRT. Biochemical (ACE and sACE2 activity, ACE concentration) and echocardiographic parameters (EF, left ventricular end-diastolic (EDD) and end-systolic diameter (ESD) and dP/dt) were measured.sACE2 activity negatively correlated with EF and positively with ESD and EDD in all patient''s populations, while it was independent in the healthy cohort. sACE2 activity was already increased in the hypertensive group, where signs for imminent heart failure (slightly decreased EF and barely increased NT-proBNP levels) were detected. sACE2 activities further increased in patients with definitive heart failure (EF<50%), while sACE2 activities decreased with the improvement of the heart failure after CRT (reverse remodeling). Serum angiotensin converting enzyme (ACE) concentrations were lower in the diseased populations, but did not show a strong correlation with the echocardiographic parameters.

Conclusions

Soluble ACE2 activity appears to be biomarker in heart failure, and in hypertension, where heart failure may be imminent. Our data suggest that sACE2 is involved in the pathomechanism of hypertension and HF.     

Insights from the clustering of microarray data associated with the heart disease

Heart failure (HF) is the major of cause of mortality and morbidity in the developed world. Gene expression profiles of animal model of heart failure have been used in number of studies to understand human cardiac disease. In this study, statistical methods of analysing microarray data on cardiac tissues from dogs with pacing induced HF were used to identify differentially expressed genes between normal and two abnormal tissues. The unsupervised techniques principal component analysis (PCA) and cluster analysis were explored to distinguish between three different groups of 12 arrays and to separate the genes which are up regulated in different conditions among 23912 genes in heart failure canines'' microarray data. It was found that out of 23912 genes, 1802 genes were differentially expressed in the three groups at 5% level of significance and 496 genes were differentially expressed at 1% level of significance using one way analysis of variance (ANOVA). The genes clustered using PCA and clustering analysis were explored in the paper to understand HF and a small number of differentially expressed genes related to HF were identified.     

干祖细胞与缺血性心脏病治疗

最近十几年,多种类型的干细胞,包括胚胎干细胞、诱导多能干细胞、骨骼肌干细胞、心脏干细胞和骨髓来源的干祖细胞等,可用于缺血性心脏病诱导的损伤修复和再生医学中,并且逐渐显示出广阔的发展前景。在此本文将介绍几种不同来源的干细胞在治疗缺血性心脏病中的研究概况,为进一步的基础研究和临床试验提供参考。     

CFC1 Mutations in Patients with Transposition of the Great Arteries and Double-Outlet Right Ventricle

Recent investigations identified heterozygous CFC1 mutations in subjects with heterotaxy syndrome, all of whom had congenital cardiac malformations, including malposition of the great arteries. We hypothesized that a subset of patients with similar types of congenital heart disease---namely, transposition of the great arteries and double-outlet right ventricle, in the absence of laterality defects---would also have CFC1 mutations. Our analysis of the CFC1 gene in patients with these cardiac disorders identified two disease-related mutations in 86 patients. The present study identifies the first autosomal single-gene defect for these cardiac malformations and indicates that some cases of transposition of the great arteries and double-outlet right ventricle can share a common genetic etiology with heterotaxy syndrome. In addition, these results demonstrate that the molecular pathway involving CFC1 plays a critical role in normal and abnormal cardiovascular development.     

Calcium-Activated Potassium Current Modulates Ventricular Repolarization in Chronic Heart Failure

The role of I_KCa in cardiac repolarization remains controversial and varies across species. The relevance of the current as a therapeutic target is therefore undefined. We examined the cellular electrophysiologic effects of I_KCa blockade in controls, chronic heart failure (HF) and HF with sustained atrial fibrillation. We used perforated patch action potential recordings to maintain intrinsic calcium cycling. The I_KCa blocker (apamin 100 nM) was used to examine the role of the current in atrial and ventricular myocytes. A canine tachypacing induced model of HF (1 and 4 months, n = 5 per group) was used, and compared to a group of 4 month HF with 6 weeks of superimposed atrial fibrillation (n = 7). A group of age-matched canine controls were used (n = 8). Human atrial and ventricular myocytes were isolated from explanted end-stage failing hearts which were obtained from transplant recipients, and studied in parallel. Atrial myocyte action potentials were unchanged by I_KCa blockade in all of the groups studied. I_KCa blockade did not affect ventricular myocyte repolarization in controls. HF caused prolongation of ventricular myocyte action potential repolarization. I_KCa blockade caused further prolongation of ventricular repolarization in HF and also caused repolarization instability and early afterdepolarizations. SK2 and SK3 expression in the atria and SK3 in the ventricle were increased in canine heart failure. We conclude that during HF, I_KCa blockade in ventricular myocytes results in cellular arrhythmias. Furthermore, our data suggest an important role for I_KCa in the maintenance of ventricular repolarization stability during chronic heart failure. Our findings suggest that novel antiarrhythmic therapies should have safety and efficacy evaluated in both atria and ventricles.     

卡维地洛联合厄贝沙坦治疗慢性心功能不全的疗效及对IL-6的影响

目的:探讨卡维地洛联合厄贝沙坦治疗慢性心功能不全的疗效及对血浆IL-6的影响。方法:选择64例慢性心功能不全患者采用平行对照法随机分为治疗组和对照组各32例,对照组给予血管扩张剂、利尿剂和强心剂等基础用药进行常规治疗,观察组在对照组的基础上加用卡维地洛联合厄贝沙坦进行治疗,疗程均为4周,观察两组患者的临床疗效、心功能分级和血浆IL-6水平变化情况。结果:4周疗程后,观察组总有效率为84.38%显著高于对照组的59.38%,差异有统计学意义(P0.05);心功能分级变化情况显示,治疗后两组患者心功能分级状况都有所变化,症状得到改善。与对照组相比观察组I级患者数量明显增加,III级数量减少,差异有统计学意义(P0.05);治疗后两组患者IL-6水平均下降,且左室射血分数(LVEF)值升高,与对照组相比观察组患者指标水平变化明显,差异有统计学意义(P0.05)。结论:在常规用药基础上加用卡维地洛和厄贝沙坦,可改善慢性心功能不全症状,降低IL-6水平,临床疗效显著。     

Chaotic Signatures of Heart Rate Variability and Its Power Spectrum in Health,Aging and Heart Failure

A paradox regarding the classic power spectral analysis of heart rate variability (HRV) is whether the characteristic high- (HF) and low-frequency (LF) spectral peaks represent stochastic or chaotic phenomena. Resolution of this fundamental issue is key to unraveling the mechanisms of HRV, which is critical to its proper use as a noninvasive marker for cardiac mortality risk assessment and stratification in congestive heart failure (CHF) and other cardiac dysfunctions. However, conventional techniques of nonlinear time series analysis generally lack sufficient sensitivity, specificity and robustness to discriminate chaos from random noise, much less quantify the chaos level. Here, we apply a ‘litmus test’ for heartbeat chaos based on a novel noise titration assay which affords a robust, specific, time-resolved and quantitative measure of the relative chaos level. Noise titration of running short-segment Holter tachograms from healthy subjects revealed circadian-dependent (or sleep/wake-dependent) heartbeat chaos that was linked to the HF component (respiratory sinus arrhythmia). The relative ‘HF chaos’ levels were similar in young and elderly subjects despite proportional age-related decreases in HF and LF power. In contrast, the near-regular heartbeat in CHF patients was primarily nonchaotic except punctuated by undetected ectopic beats and other abnormal beats, causing transient chaos. Such profound circadian-, age- and CHF-dependent changes in the chaotic and spectral characteristics of HRV were accompanied by little changes in approximate entropy, a measure of signal irregularity. The salient chaotic signatures of HRV in these subject groups reveal distinct autonomic, cardiac, respiratory and circadian/sleep-wake mechanisms that distinguish health and aging from CHF.     

血清降钙素原(PCT)检测对于老年心衰抗感染治疗的指导意义分析

目的:探讨血清降钙素原(PCT)对于老年心衰患者抗感染治疗中的指导意义。方法:选取我院于2013年1月-2014年6月间收治的130例老年心衰患者,将其随机分为观察组以及对照组,每组65例,对照组根据患者的病情变化决定是否使用抗菌药物,而观察组根据PCT变化决定是否使用抗菌素治疗。比较2组患者的体温、PCT、WBC、CRP变化情况,治疗效果,住院情况以及抗菌素使用情况。结果:观察组在使用抗菌药物当日的PCT水平明显低于入院时,P0.05,而体温、WBC、CRP水平比较无明显差异,使用抗菌药物3 d后,血清PCT水平相比于使用抗菌素当日明显下降,体温相比于入院时显著下降,P0.05。观察组的二重感染率明显低于对照组,P0.05,观察组的抗菌药物使用疗程、费用以及总住院费用均明显低于对照组,组间比较有明显差异,P0.05。结论:PCT指标应用于老年心衰患者应用抗菌素的指导治疗,能够减少抗菌药物的使用量,降低住院费用,减少住院时间,减少二重感染的发生率。     

手术治疗先天性心脏病患者活动期心内膜炎的相关因素

目的:确定先天性心脏病活动期感染性心内膜炎(active infective endocarditis,AIE)的手术指征。方法:于2003-2011年从71个机构数据库中调查并采集247例患有感染性心内膜炎的儿童及成人先天性心脏病(congenital heart disease,CHD)患者数据,其中74例(30%)进行了AIE手术治疗。回顾性分析患者的年龄、性别、感染心内膜炎前对CHD的诊断、致病微生物和感染部位等数据。结果:与AIE手术治疗必要性显著相关的指标是感染性心内膜炎(infective endocarditis,IE)病发前对心脏异常的诊断缺乏、主动脉瓣IE、瓣周脓肿、心力衰竭以及抗生素发生变化。逐步逻辑回归方程分析结果表明瓣周脓肿、心力衰竭以及抗生素改变是先天性心脏病患者进行AIE手术治疗必要性的独立决定因素。结论:对IE合并CHD的患者而言,当心力衰竭、瓣周脓肿或抗生素变化发生时,手术可作为治疗AIE的一种手段。     

Nerve Growth Factor Stimulates Cardiac Regeneration via Cardiomyocyte Proliferation in Experimental Heart Failure

Although the adult heart likely retains some regenerative capacity, heart failure (HF) typically remains a progressive disorder. We hypothesise that alterations in the local environment contribute to the failure of regeneration in HF. Previously we showed that nerve growth factor (NGF) is deficient in the failing heart and here we hypothesise that diminished NGF limits the cardiac regenerative response in HF. The capacity of NGF to augment cardiac regeneration was tested in a zebrafish model of HF. Cardiac injury with a HF phenotype was induced in zebrafish larvae at 72 hours post fertilization (hpf) by exposure to aristolochic acid (AA, 2.5 µM, 72–75 hpf). By 168 hpf, AA induced HF and death in 37.5% and 20.8% of larvae respectively (p<0.001). NGF mRNA expression was reduced by 42% (p<0.05). The addition of NGF (50 ng/ml) after exposure to AA reduced the incidence of HF by 50% (p<0.01) and death by 65% (p<0.01). Mechanistically, AA mediated HF was characterised by reduced cardiomyocyte proliferation as reflected by a 6.4 fold decrease in BrdU+ cardiomyocytes (p<0.01) together with features of apoptosis and loss of cardiomyocytes. Following AA exposure, NGF increased the abundance of BrdU+ cardiomyocytes in the heart by 4.8 fold (p<0.05), and this was accompanied by a concomitant significant increase in cardiomyocyte numbers. The proliferative effect of NGF on cardiomyocytes was not associated with an anti-apoptotic effect. Taken together the study suggests that NGF stimulates a regenerative response in the failing zebrafish heart, mediated by stimulation of cardiomyocyte proliferation.     

心力衰竭的物理诊断现状

心力衰竭是各种心脏疾病发展的终末阶段,及时准确的确诊心力衰竭、辨别其病情变化可进一步指导治疗及缩短住院时间,并为心力衰竭的预后评价提供参考依据。目前,确诊心力衰竭主要基于患者的临床症状、体征及各种影像学表现、生化指标等做出综合评价,而物理诊断是诊断心力衰竭不可或缺的依据。心脏彩超已应用于临床多年,可从多个层面评估左室充盈压,是初步评价心脏功能的便捷措施。核心脏病学可评估心脏交感神经支配的区域及激活模式,预测心力衰竭的发病率和死亡率。心脏磁共振可用于进行危险分层及确定是否适合手术/介入治疗。此外,心脏CT及心导管术也是用于评价心功能的常见物理检查方法。本文主要总结了目前各种诊断心力衰竭的物理诊断方法的最新进展,以进一步指导临床实践。     

Transcatheter leadless permanent pacemaker in complex congenital heart disease with interrupted inferior vena cava: A challenging implantation

31 years lady with complete atrioventricular canal defect, large primum atrial septal defect (ASD), inlet ventricular septal defect (VSD) and Eisenmenger syndrome, presented with atrial flutter and complete heart block. She was not suitable for corrective cardiac surgery and not yet indicated for heart-lung transplantation. She was advised single chamber permanent pacemaker and eventually Micra VR transcatheter leadless pacemaker was finalised for her. Transcatheter leadless pacemaker was deployed in her RV septum despite some unforeseen technical problems. This patient had intrahepatic interruption of IVC with Azygous continuation draining into SVC but this altered venovascular course was detected only fluoroscopically midway during the pacemaker implantation procedure and this was not detected in the preprocedural transthoracic echocardiography. This abnormal venous course was clearly demonstrated in the cardiac CT which was performed only after completion of the pacemaker implantation procedure in this patient. The technical challenges encountered mainly were mostly during the manipulation of the 27F delivery catheter of Micra through this altered cardiovascular anatomy via transfemoral approach and also due to the presence of septal defects. Thus, transcatheter leadless permanent pacemaker was implanted successfully through transfemoral access in this complex congenital heart disease with interrupted IVC and azygous continuation. Besides transthoracic echocardiography, it may be better to perform transesophageal echocardiography or even preferably radiological imaging like cardiac CT or MRI prior to transcatheter leadless pacemaker implantation in patients with complex congenital heart disease to understand the cardiovascular anatomy and plan the procedure.     

先天性心脏病患儿介入封堵术治疗前后CRP、NT-proBNP、心率变异性的变化及与术后心功能的关系研究

摘要 目的：探讨先天性心脏病（CHD）患儿介入封堵术治疗前后C-反应蛋白（CRP）、N末端B型利钠肽原（NT-proBNP）、心率变异性（HRV）的变化及与术后心功能的关系。方法：选择2020年10月至2021年6月在本院行介入封堵术治疗的95例CHD患儿为研究对象,采用化学发光法检测血清CRP水平,采用电化学发光免疫技术检测血清NT-proBNP水平,采用24 h动态心电图及12导联同步心电图分析HRV指标,观察手术前后患儿的血清CRP、NT-proBNP水平及HRV指标变化,比较术后不同NYHA心功能分级患儿的血清CRP、NT-proBNP水平和HRV指标,分析患儿术前血清CRP水平、血清NT-proBNP水平、HRV指标与术后NYHA心功能分级的相关性。结果：介入封堵术后患儿血清CRP、NT-proBNP、LF/HF水平逐渐降低,术后3 d、术后1个月时均低于术前,术后1个月时均低于术后3 d时（P<0.025）;而TP、HF、LF、R-R、PNN50%、ASDNN、SDANN、SDNN、rMSSD水平逐渐升高,术后3 d、术后1个月时均高于术前,术后1个月时均高于术后3 d 时（P<0.025）。患儿术后3 d的血清CRP、NT-proBNP水平及LF/HF水平随着NYHA心功能分级的升高而升高,TP、HF、LF、R-R、PNN50%、ASDNN、SDANN、SDNN、rMSSD水平随着NYHA心功能分级的升高而降低（多有P＜0.05）。患儿术后3 d的NYHA心功能分级与治疗前血清CRP、NT-proBNP及LF/HF水平呈负相关,与TP、HF、LF、R-R、PNN50%、ASDNN、SDANN、SDNN、rMSSD水平呈正相关（P＜0.05）。结论：CHD患儿经介入封堵术治疗后,血清CRP、NT-proBNP及HRV指标变化明显,与术后NYHA心功能分级显著相关,血清CRP、NT-proBNP及HRV指标有望成为评估CHD患儿介入封堵术后预后的较敏感性指标。     

沙库巴曲缬沙坦联合呋塞米治疗慢性心力衰竭的疗效研究

目的:探究沙库巴曲缬沙坦联合呋塞米治疗慢性心力衰竭的临床疗效。方法:选择2017年1月-2018年12月于我院诊治的慢性心力衰竭患者60例,随机将其分为两组。其中,对照组给予呋塞米进行治疗,研究组在对照组基础上联合沙库巴曲缬沙坦进行治疗,对比两组患者的治疗总有效率、治疗前后心功能、血清N端B型脑钠肽(NT-proBNP)、醛固酮(ALD)、细胞间黏附分子-1(ICAM-1)水平的变化及不良反应的发生情况。结果:治疗后,研究组患者的治疗总有效率[96.7%(29/30)]显著高于对照组[80.0%(24/30)](P0.05)。两组患者治疗后的左心室射血分数(LVEF)均较治疗前显著升高,左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)均较治疗前明显降低(P0.05),且研究组LVEF显著高于对照组,而LVEDD和LVESD明显低于对照组(P0.05);两组患者治疗后的血清NT-proBNP、ALD、ICAM-1水平均较治疗前显著降低(P0.05),且研究组以上指标均显著低于对照组低(P0.05)。对照组患者不良反应发生率[10.0%(3/30)]与研究组[13.3%(4/30)]比较无显著性差异(P0.05)。结论:沙库巴曲缬沙坦联合呋塞米治疗慢性心力衰竭的效果显著优于单用呋塞米治疗,其可有效改善患者的心功能且安全性较高,可能与其明显改善患者血清NT-proBNP、ALD、ICAM-1水平有关。     

Transvenous pacing in complex post-operative congenital heart disease guided by angiography: A case report

Transvenous pacing in patients with postoperative complex congenital heart disease (CHD) can be challenging and pose technical challenges to lead placement because of the complex anatomy, distortions produced by the surgical procedures, and the altered relationship of cardiac chambers. We describe the utility of angiography for transvenous dual chamber pacemaker implantation in a post-operative complex congenital heart disease.     

Apoptosis in heart failure: a tale of heightened expectations, unfulfilled promises and broken hearts...

Although apoptosis contributes significantly to remodeling of the fetal heart during evolution of cardiac chambers and correct routing of the great vessels, it has been believed that apoptosis does not occur in terminally differentiated adult cardiac muscle cells. However, apoptosis has recently been demonstrated in animal models of heart failure as well as in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation. Ventricular dilatation and neurohormonal activation, the hall-marks of heart failure, lead to upregulation of transctription factors, induce muscle cell hypertrophy and prepare cells for entry into the cell-division cycle. However, since terminally differentiated myocytes cannot divide, they die by apoptosis. It has been proposed that low-grade apoptosis in failing heart may be responsible for inexorable decline in left ventricular function. Better understanding of the molecular and cellular basis of apoptosis in the failing myocardium may lead to development of strategies aimed at preventing progressive myocyte loss and deterioration in left ventricular function.