Device Therapy for Heart Failure

Surgical approaches to heart failure (HF) management have become a necessary strategy in response to a waiting list that is expanding in the face of a limited supply of organ donors. Multiple studies have supported the safety and efficacy of device-based therapy. Among the device-based therapy options, ventricular assist devices (VADs) represent an alternative to heart transplantation with the capability to function as short-term support, bridge-to-transplantation or recovery and as long-term support. VAD support may be considered in those with refractory cardiogenic shock or those with decompensated chronic HF that is unresponsive to maximized medical therapy. Composite scoring scales may be used to risk-stratify patients using clinical and laboratory values to allow more systematic patient selection. As the pursuit for a perfect device continues, so does the search for the best objective index to guide referral. Technologic advances will enhance device performance and extend VAD use into community practice. This discussion aims to highlight criteria for candidate selection and referral for VAD implantation.     

Pharmacotherapeutic Management of Gastrointestinal Bleeding in Patients with Continuous‐Flow Left Ventricular Assist Devices

Continuous‐flow left ventricular assist devices (CF‐LVADs) have become an integral component of the management in patients with advanced heart failure, serving as destination therapy or as a bridge to heart transplantation. Despite significant advances in the design and longevity of the device, the ongoing risk for bleeding remains a significant concern. The genesis of gastrointestinal bleeding (GIB) in patients with CF‐LVADs is likely multifactorial and may include components of acquired von Willebrand disease, angiodysplasia, and gastrointestinal arteriovenous malformations, as well as additional risk factors such as history of GIB and increased age. Several pharmacotherapy options have been used, but the data surrounding their overall efficacy remain sparse. The necessity for larger prospective studies is essential to further advance the management of this devastating complication. Within this review, we discuss the known pathophysiologic process of CF‐LVAD–related GIB and highlight the therapeutic options discussed within the literature. In addition, we discuss potential therapeutic options based on mechanisms of action as they correlate to known pathophysiologic processes of CF‐LVAD–related GIB. Finally, we provide recommendations for constructing drug therapy regimens in patients with CF‐LVADs who develop GIB.     

国产气动搏动性心室辅助装置的体外流体力学及动物实验观察

目的 对我国自主研发气动搏动性心室辅助装置进行体外流体力学检验及活体动物应用实验, 检验其是否满足临床心室辅助装置要求。方法 通过体外模拟循环实验台, 30%甘油水溶液作为循环介质, 接入心室辅助装置, 测定不同模式下血泵的后负荷和流量, 以此检测装置的流体力学效果。对 6 只实验犬应用心室辅助装置左心辅助模式 1 h, 之后药物 KCl 诱颤心脏, 5 min 后除颤。监测心室辅助装置对实验犬的心率、 血压支持效果。结果 心室辅助装置流体力学实验后负荷 100 mmHg 条件下, 流量可达到 4 L/min 以上。实验犬经左室安装辅助装置后, 各时间点心率无明显变化。辅助后即刻与辅助前相比收缩压升高约 30 mmHg, 舒张压升高约 19 mmHg。辅助过程中未见明显血压波动。诱颤后可维持收缩压 60 mmHg, 除颤后撤除装置存活良好。结论该心室辅助装置所产生的流体压力可基本满足临床心室辅助要求, 短期应用于实验犬有效、 安全、 稳定, 长期使用效果尚需进一步实验证明。     

The pharmacotherapy implications of ventricular assist device in the patient with end-stage heart failure

Advances in mechanical circulatory support, such as the use of ventricular assist devices (VADs), have become a means for prolonging survival in end-stage heart failure (HF). VADs decrease the symptoms of HF and improve quality of life by replacing some of the work of a failing heart. They unload the ventricle to provide improved cardiac output and end-organ perfusion, resulting in improvement in cardiorenal syndromes and New York Heart Association functional class rating. VADs are currently used asa bridge to heart transplantation, a bridge to recovery of cardiac function, or as destination therapy. Complications of VAD include bleeding, infections, arrhythmias, multiple organ failure, right ventricular failure, and neurological dysfunction. Patients with VAD have unique pharmacotherapeutic requirements in terms of anticoagulation, appropriate antibiotic selection, and continuation of HF medications. Pharmacists in acute care and community settings are well prepared to care for the patient with VAD. These patients require thorough counseling and follow-up with regard to prevention and treatment of infections, appropriate levels of anticoagulation, and maintenance of fluid balance. A basic understanding of this unique therapy can assist pharmacists in attending to the needs of patients with VAD.     

Thyroid hormone and chronically unloaded hearts

The heart is subjected to chronic mechanical unloading during prolonged spaceflight and microgravity. The heart in patients with end-stage heart failure is also unloaded in prolonged duration after left ventricular assist devices (LVAD) are implanted. Heterotopic heart transplantation in rats is an established model of chronic cardiac unloading, and has been used to investigate the effects of chronic cardiac unloading on the heart. Observations that have been found using this experimental model are as follow. Chronic cardiac unloading induces time-dependent depressions of Ca²⁺ handling and myocyte contractility, which are associated with the shift of myosin heavy chain (MHC) isozymes and altered expressions of Ca²⁺ cycling-related proteins. Treatment with the physiological treatment dose of thyroid hormone restores the expression levels of Ca²⁺ cycling-related proteins, Ca²⁺ handling, and contractile function of cardiac myocytes in chronically unloaded hearts. Although future studies are required to determine precise mechanisms of the beneficial effects of thyroid hormone on chronically unloaded hearts, these observations may have clinical implications in the future for chronic cardiac unloading in the space industry as well as in the treatment of patients with end-stage heart failure supported by LVAD.     

An approach to the treatment of pediatric myocarditis

The newest treatment strategies for pediatric myocarditis have evolved from an understanding of the pathophysiology of myocyte damage. Although the initial stages of viral myocarditis apparently result from the direct cytopathic effects on the atrial and ventricular myocardium, later stages of progressive decompensation result from immune-mediated myocyte destruction common to many forms of myocarditis. Despite advances in the understanding of the role of genetics, immunologic mechanisms, and infectious causes of myocarditis, supportive therapy continues to remain the cornerstone of treatment. Presently, therapies include supportive management with anticongestive agents, antiviral medications, and therapies that attempt to interrupt the immunologic cascade. Clinical studies have yet to provide convincing evidence that the use of immunosuppressants and gamma-globulin favorably alters the outcome for pediatric patients with acute myocarditis. Ventricular assist devices and heart transplantation remain as treatment options for all pediatric patients with severe myocarditis resistant to all other therapies. Although this review will focus on viral myocarditis, the supportive strategies and surgical treatment options apply to most forms of cardiomyopathy.     

原位心脏移植术后多普勒超声心动图的重要性评价

目的 评价多普勒超声心动图在原位心脏移植术后的作用，以避免心内膜下心肌活检带来的损害。方法 2例心脏移植术后患者应用多普勒超声心动图仪进行床边的密切跟踪，随时记录心脏移植术后的解剖结构、心脏血流动力学特别是二尖瓣E、A峰的变化等综合判断可能出现的排斥反应情况。结果 术后明显特征改变是供、受体心房缝合缘的清楚显示，及右心房上下径增大；右室短期内肥厚扩大，1例出现室间隔和左室后壁一过性增厚；心包积液的出现，以扩张性心肌病心脏移植术后增加明显；房室瓣返流及1例出现主动脉瓣返流。本组2例心脏收缩功能正常及舒张功能一过性轻度降低，二尖瓣E、A峰轻度变化。结论 心脏移植术后处理是确保心脏移植成功的关键。多普勒超声心动图可在术后24小时开始检测跟踪，随时准确地提供以上各项指标变化，对临床治疗决策有重要意义。     

调脂治疗对慢性心力衰竭患者左室舒张功能及运动耐量的影响

目的:应用他汀类调脂药物,通过观察其对慢性心力衰竭患者左室舒张功能、血浆N-端脑钠肽前体(Nt-proBNP)及运动耐量等指标的影响,探讨调脂药物对慢性心力衰竭患者的治疗作用。方法:将符合入选标准的慢性心衰患者随机分为2组,治疗组(标准治疗+调脂治疗)和对照组(标准治疗),均于治疗前后进行肝肾功能、血脂分析、血液流变学等常规检查。疗程6个月。对2组患者左室舒张功能、Nt-proBNP及运动耐量进行比较分析。结果:与治前比较,2组患者心功能分级均较治前明显改善,但组间比较差异无显著性;与治前比较,2组患者左室舒张功能(VE/VA)均改善(P<0.05),治疗组改善幅度优于对照组(P<0.05);与治前比较,2组患者Nt-proBNP浓度均降低(P<0.01),治疗组下降幅度优于对照组(P<0.01);与治前比较,2组患者运动耐量(6分钟步行距离测定)均有提高(P<0.05),治疗组略优于对照组,但差异无显著性;与治前比较,2组患者全血黏度、纤维蛋白原均有改善(P<0.05),治疗组略优于对照组,但差异无显著性。结论:在标准抗心衰治疗的基础上加用调脂药物,能进一步改善慢性心力衰竭患者的左室舒张功能,但对左室射血分数和运动耐量的改善与标准抗心衰治疗无差异。     

4例行左心室辅助装置植入术患者的围术期抗栓治疗分析

临床药师通过监护4例既往长期抗血栓治疗,拟行左心室辅助装置植入术患者的围术期抗血栓治疗,旨在总结该类患者围术期抗血栓治疗的监护重点。结果提示,临床药师以术前讨论的方式,评估患者血栓与出血风险,制定手术前抗血栓药物的停药与桥接时机,且通过药学监护,调整术后抗血栓药物的剂量与给药时机,识别药物相互作用,可降低患者围术期血栓与出血事件发生率。     

Therapeutic Anticoagulation With an Ultra-Low Concentration Argatroban-Based Purge Solution for Percutaneous Ventricular Assist Device in Patient With Heparin-Induced Thrombocytopenia

Purpose/Background: Percutaneous left ventricular assist devices (pVADs) require a continuous purge solution containing heparin to prevent pump thrombosis and device failure. Data regarding alternative options in patients who have suspected heparin-induced thrombocytopenia (HIT) are limited. Methods: In this report, we describe a 68-year-old white man with cardiogenic shock with an Impella CP device managed with a low concentration argatroban-based purge solution secondary to a suspected diagnosis of HIT. Results: The purge solution was initiated as argatroban in dextrose 10% at a concentration of 0.12 mg/mL and was subsequently decreased twice to 0.06 and 0.015 mg/mL based on the patient’s clinical course. Conclusions: This case report describes the safe and effective use of argatroban purge solution necessary for anticoagulation although further studies are needed to confirm these findings.     

Cardiac Resynchronization Therapy in Patients with Chronic Heart Failure

Congestive heart failure afflicts 2 to 4 million people in the US and nearly 15 million people worldwide. Accepted goals of heart failure treatment include: (i) improvement of symptoms; (ii) prevention of disease progression; and (iii) reduction in morbidity and mortality. Complex pharmacological therapies achieve these goals, but not in all patients with heart failure. Cardiac resynchronization therapy (CRT) represents a new therapeutic approach in patients with chronic heart failure. CRT is only applicable to a subgroup of patients with ventricular conduction system delay, characterized by prolonged QRS duration. Bundle branch block impacts 20 to 30% of patients with New York Heart Association (NYHA) functional class III–IV heart failure and consists predominantly of left bundle branch block. When left ventricular (LV) conduction delay is superimposed upon ventricular dysfunction, it appears to be a marker of disease severity. These conduction abnormalities have deleterious effects both on systolic function and LV filling, and they can induce or enhance mitral functional regurgitation. CRT attempts to correct the deleterious effect of dysynchrony by increasing LV filling time, decreasing septal dyskinesis and reducing mitral regurgitation. Several observational studies and randomized, controlled trials have shown the benefit of CRT in a subgroup of patients with heart failure, with conduction delays. Improvements were found in the mean distance walked in 6 minutes, quality of life (QOL), NYHA functional class, in peak oxygen uptake (V?O₂), total exercise time, reduction of hospitalization, LV function and reduction of the LV end-diastolic diameter. These studies support the therapeutic value of ventricular resynchronization in patients with severe heart failure, who have intraventricular conduction delay but who do not have a standard indication for the implantation of a pacemaker. In respect to these study results, possible indications for a biventricular pacing device at this time are as follows: NYHA functional class III, LV ejection fraction <35%, sinus rhythm, QRS duration >150 msec and drug refractory despite individual optimal heart failure therapy. CRT significantly improved symptoms, exercise tolerance and QOL in most patients. However, further studies are needed to assess long-term clinical effects and prognosis, as well as economic benefit of this therapeutic approach.     

曲美他嗪联合运动疗法对冠心病经皮冠状动脉介入术后患者心脏康复的影响

目的：探讨曲美他嗪联合运动疗法对冠心病经皮冠状动脉介入（PCI）术后患者心脏康复作用的影响。方法：纳入冠心病PCI术后1个月内的患者90例,随机分成治疗A组、治疗B组及对照组,每组各30例。A组在冠心病二级预防治疗的基础上加用曲美他嗪并联合运动疗法、B组在冠心病二级预防治疗的基础上加用曲美他嗪、对照组仅给予冠心病二级预防治疗。观察期为6个月。监测3组患者的6 min步行试验（6MWT）的距离、6MWT时的心率及动脉血氧饱和度、左室舒张末期内径（LVEDD）、左室收缩末期内经（LVESD）、左室间隔厚度（LVIVS）、左心室后壁厚度（LVPWT）、左室射血分数（LVEF）及正常舒张功能的比例。结果：组内比较：与治疗前相比,3组的6MWT的距离明显增多、6MWT时的心率明显降低、正常舒张功能的比例明显升高并且LVEF明显增加,差异具有统计学意义（P<0.05）。治疗后组间比较：A组分别与B组及对照组相比,6MWT的距离明显增加、6MWT时的心率明显降低、正常舒张功能的比例明显升高且左室射血分数明显增加,差异具有统计学意义（P<0.017）;B组与对照组相比,治疗后LVEF明显增加,差异具有统计学意义（P<0.017）,6MWT的距离、6MWT时的心率及正常舒张功能的比例两组无明显改善（P>0.05）。结论：曲美他嗪联合运动疗法对冠心病PCI术后患者的心脏康复效果优于常规的冠心病二级预防治疗。     

β-blockers in heart failure: recently completed and ongoing clinical trials

β-blockers have emerged as an important therapy in patients with symptomatic left ventricular systolic dysfunction. Early studies demonstrated that β-blocker therapy improved left ventricular function, reduced neurohumoral activity and reduced heart failure symptoms in these patients. While none of these small studies demonstrated a significant benefit in terms of overall survival, several meta-analyses suggested that β-blocker therapy could, in fact, reduce mortality in patients with left ventricular systolic dysfunction and mild to moderate heart failure symptoms (New York Heart Association class II or III). Three large, recently completed, trials have confirmed the benefit of β-blockade in these patients. This report reviews some of the initial clinical studies of β-blockade in heart failure, examines the findings of the three large multicentre trials and other relevant research. Finally, ongoing trials designed to assess the relative efficacy of different β-blockers and evaluate the utility of β-blockade in specific subsets of patients with heart failure are discussed.     

曲美他嗪对老年冠心病合并糖尿病患者心脏舒张功能的影响简

目的探讨曲美他嗪对老年冠心病合并糖尿病患者心脏舒张功能的影响。方法将126例舒张功能不全的老年冠心病合并糖尿病患者,随机分成常规口服药物组60例（对照组）和曲美他嗪组66例（治疗组）。2组患者均给予降糖、冠心病二级预防用药,治疗组在运用上述药物治疗的基础上加用曲关他嗪口服,每次20mg,每日3次。治疗3个月观察患者血糖水平及超声心动图指标的变化。结果治疗组治疗后心脏舒张功能、左心室射血分数与治疗前相比较均有改善,差异有统计学意义（P〈0．01）;而对照组治疗前后心脏舒张功能、左心室射血分数差异无统计学意义（P〉0．05）;2组治疗后比较差异有统计学意义（P〈0．01）。结论曲美他嗪能改善老年冠心病合并糖尿病患者的心脏舒张功能及收缩功能,并且安全性较好。     

左旋卡尼汀对慢性心力衰竭患者心功能及血浆脑钠肽的影响

目的：评价左旋卡尼汀（L—CN）对慢性心力衰竭患者心功能及血浆脑钠肽（BNP）的影响。方法：将60例慢性心力衰竭患者随机分为对照组30例和治疗组30例,对照组给予地高辛、利尿剂、血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗剂及B受体阻滞剂治疗,治疗组在此基础上加用国产左旋卡尼汀3g静脉滴注,1次,d,连续用药14d。观察治疗前及治疗后患者的心功能及BNP变化。结果：与治疗前相比,治疗组的左心室短轴缩短率（LVFS）、左心室射血分数（LVEn、BNP值明显改善,左心室舒张末内径（LVEDD）下降,但无统计学意义;与对照组比较,治疗组的显效率和总有效率均高于对照组,LVFS、LVEF、BNP值差异显著。结论：左旋卡尼汀能改善慢性心力衰竭患者的心功能。可以作为心力衰竭的辅助治疗。     

高压氧对高血压性心脏病左心室舒张功能的影响

目的探讨高压氧对高血压性心脏病左心室舒张功能的影响。方法随机将60例高血压性心脏病患者分为两组,其中30例在常规药物治疗基础上加用高压氧治疗为治疗组,30例应用常规药物治疗为对照组,治疗前后进行彩色多普勒超声检测。结果治疗组行高压氧治疗后,左室舒张功能指标（E、A、E／A、DT）明显改善（P〈0．01）,与对照组比较差异有统计学意义（P〈0．05）。其中治疗后,治疗组E／A为（1．08±0．12）,LVMI（g·m2）为（128．1±7．5）;对照组分别为（0．98．O．06）,（133．5±8．3）。结论高压氧治疗可显著改善高血压性心脏病左心室舒张功能     

贝那普利对慢性充血性心力衰竭患者左心室及血管内皮功能的影响

目的探讨贝那普利对慢性充血性心力衰竭患者左心室及血管内皮功能的影响。方法选取268例慢性充血性心力衰竭,随机分为常规治疗组130例采取常规治疗,贝那普利组138例采取常规治疗联合贝那普利治疗,观察两组治疗前后血管内皮功能测定、左室舒张末内径(LVDd)、左心室射血分数(LVEF)并进行比较。结果两组治疗后FMD、左室舒张末内径、射血分数比较差异有统计学意义(P<0.05)。结论慢性充血性心力衰竭应用贝那普利可以有效的逆转左室重塑,改善左心室功能、血管内皮功能,改善血流动力学,减轻心力衰竭,改善患者的生活质量。     

beta-blockers in heart failure: recently completed and ongoing clinical trials

beta-Blockers have emerged as an important therapy in patients with symptomatic left ventricular systolic dysfunction. Early studies demonstrated that beta-blocker therapy improved left ventricular function, reduced neurohumoral activity and reduced heart failure symptoms in these patients. While none of these small studies demonstrated a significant benefit in terms of overall survival, several meta-analyses suggested that beta-blocker therapy could, in fact, reduce mortality in patients with left ventricular systolic dysfunction and mild to moderate heart failure symptoms (New York Heart Association class II or III). Three large, recently completed, trials have confirmed the benefit of beta-blockade in these patients. This report reviews some of the initial clinical studies of beta-blockade in heart failure, examines the findings of the three large multicentre trials and other relevant research. Finally, ongoing trials designed to assess the relative efficacy of different beta-blockers and evaluate the utility of beta-blockade in specific subsets of patients with heart failure are discussed.     

曲美他嗪改善冠心病合并糖尿病患者左室功能的疗效观察

目的 探讨曲美他嗪改善冠心病合并糖尿病患者左室功能的作用。方法 41例合并冠心病和糖尿病的心功能不全患者随机分为2组,对照组21例给予常规治疗,治疗组20例在常规治疗基础上加用口服曲美他嗪20 mg,3次/d。12周后观察NYHA心功能分级及超声心动图指标的变化。结果 与对照组相比,治疗组心功能分级明显改善（P〈0.05）,左室射血分数（LVEF）有明显提高（P〈0.05）,左室舒张末期内径（LVEDD）明显缩小（P〈0.05）。结论 合并糖尿病的冠心病左心衰患者治疗上加用曲美他嗪能明显改善患者的左心功能。