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.     

心力衰竭患者高凝状态与抗栓治疗

心力衰竭(HF)患者脑卒中、肺栓塞及外周静脉血栓等血栓栓塞事件的发生率明显高于非HF患者。其抗栓治疗一直存在争议,主要权衡抗栓(抗凝和抗血小板)治疗、血栓栓塞风险降低的获益和出血的风险。多项研究已证实,有心房颤动或血栓栓塞史的HF患者需要进行常规抗凝治疗,但窦性心律HF患者是否需要进行预防性抗栓治疗目前还没有达成共识。     

心力衰竭治疗新靶点-Galectins．3

尽管心力衰竭（HF）的药物治疗近年来有了较大进展,但HF患者预后仍很差。针对HF发病早期行药物治疗是近年来研究的一个重点。Galectin．3（Gal-3）在心室重塑和HF病理生理发展过程中起重要作用,可作为HF治疗的靶点。Gal-3水平升高的HF患者可从醛固酮拮抗剂治疗中获益。本文简要综述以Gal-3水平为指导的HF患者个体化治疗。     

Pharmacological Prevention of Thromboembolism in Patients with Left Ventricular Dysfunction

Chronic left ventricular systolic dysfunction is a well recognized problem with an increasingly significant impact on healthcare in the form of congestive heart failure (CHF). Advances in medicine have led to improved survival after myocardial infarction (MI) and as a result, an increased prevalence of left ventricular systolic dysfunction. An increased incidence of thromboembolism, especially stroke, in patients with left ventricular systolic dysfunction is also well recognized. Pharmacological strategies to prevent stroke have been proposed in numerous studies. For example, anticoagulation in patients with atrial fibrillation and heart failure has been shown to reduce mortality rates and the incidence of stroke; however, its role in patients with left ventricular dysfunction and normal sinus rhythm is unclear and utilization of anticoagulation in these patients varies widely. The role of aspirin to prevent thromboembolism in patients with CHF is controversial. The relatively new pharmacological agent ximelagatran, which has an advantage of unmonitored oral administration has the potential to change the anticoagulation strategy in patients with heart failure. Important trials to define optimal therapy for reducing the risk of thromboembolism and death in patients with left ventricular systolic dysfunction and sinus rhythm include the recently reported WATCH (Warfarin and Antiplatelet Therapy in Chronic Heart failure) trial and the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial, which is currently underway. The WATCH trial failed to outline significant differences between aspirin (acetylsalicylic acid), warfarin, and clopidogrel in the primary composite endpoint of all-cause mortality, nonfatal MI, and nonfatal stroke. Combined data from WATCH and WARCEF may provide sufficient statistical power to clarify outcomes such as stroke and death in patients with reduced cardiac ejection fraction. The pooled data may also help define optimal preventative measures for thromboembolism in patients with left ventricular systolic dysfunction and sinus rhythm.     

Wound healing and catheter thrombosis after implantable venous access device placement in 266 breast cancers treated with bevacizumab therapy

The aim of this study was to determine, in a population with metastatic breast cancer treated with bevacizumab therapy, the incidence of wound dehiscence after placement of an implantable venous access device (VAD) and to study the risk of catheter thrombosis. This study enrolled all VADs placed by 14 anesthetists between 1 January 2007 and 31 December 2009: 273 VADs in patients treated with bevacizumab therapy and 4196 VADs in patients not treated with bevacizumab therapy. In the bevacizumab therapy group, 13 cases of wound dehiscence occurred in 12 patients requiring removal of the VAD (4.76%). All cases of dehiscence occurred when bevacizumab therapy was initiated less than 7 days after VAD placement. Bevacizumab therapy was initiated less than 7 days after VAD placement in 150 cases (13 of 150: 8.6%). The risk of dehiscence was the same from 0 to 7 days. In parallel, the VAD wound dehiscence rate in patients not receiving bevacizumab therapy was eight of 4197 cases (0.19%) (Fisher's test significant, P<0.001). No risk factors of dehiscence were identified: anesthetists, learning curves, and irradiated patients. VAD thrombosis occurred in four patients (1.5%). In parallel, VAD thrombosis occurred in 51 of 4197 patients (1.2%) not receiving bevacizumab therapy (Fisher's test not significant; P=0.43). Bevacizumab therapy was permanently discontinued in five patients related to wound dehiscence and in one patient due to extensive skin necrosis. These data suggest the need to observe an interval of at least 7 days between VAD placement and initiation of bevacizumab therapy to avoid the risk of a wound dehiscence requiring chest wall port explant. The risk of VAD thrombosis does not require any particular primary prevention.     

Energy metabolism disorders and potential therapeutic drugs in heart failure

Heart failure (HF) is a global public health problem with high morbidity and mortality. A large number of studies have shown that HF is caused by severe energy metabolism disorders, which result in an insufficient heart energy supply. This deficiency causes cardiac pump dysfunction and systemic energy metabolism failure, which determine the development of HF and recovery of heart. Current HF therapy acts by reducing heart rate and cardiac preload and afterload, treating the HF symptomatically or delaying development of the disease. Drugs aimed at cardiac energy metabolism have not yet been developed. In this review, we outline the main characteristics of cardiac energy metabolism in healthy hearts, changes in metabolism during HF, and related pathways and targets of energy metabolism. Finally, we discuss drugs that improve cardiac function via energy metabolism to provide new research ideas for the development and application of drugs for treating HF.KEY WORDS: Heart failure, Energy deficit, Cardiac dysfunction, Energy metabolism, Substrate metabolism, Hormones, Natural products, Synthetic drugs     

Drug Treatment of Patients with Decompensated Heart Failure

Decompensated heart failure (HF) may be defined as sustained deterioration of at least one New York Heart Association functional class, usually with evidence of sodium retention. Episodes of decompensation are most commonly precipitated by sodium retention, often associated with medication noncompliance. Our therapeutic approach to hospitalized patients is based on the documented hemodynamic responses to vasodilator therapy, with redistribution of mitral regurgitant flow to forward cardiac output and decompression of the left atrium. Invasive hemodynamic monitoring is seldom required for the effective management of patients with HF and there are risks associated with pulmonary artery catheterization. The currently available parenteral vasoactive drugs for decompensated heart failure include: (i) vasodilators such as nesiritide, nitroprusside and nitroglycerin (glyceryl trinitrate); (ii) catecholamine inotropes, primarily dobutamine; and (iii) inodilators such as milrinone, a phosphodiesterase inhibitor. Vasodilators are most appropriate for those patients who are primarily volume-overloaded, but with adequate peripheral perfusion. In this class of agents, nesiritide (recombinant human B-type natriuretic peptide) offers advantages over currently available drugs. Nesiritide produces rapid and sustained decreases in right atrial and pulmonary capillary wedge pressures, with reduction in pulmonary and systemic vascular resistance and increases in cardiac index. The hemodynamic effects of nesiritide infusion were sustained over a duration of 1 week and the drug may be used without intensive monitoring in patients with decompensated HF. Treatment with dobutamine is indicated in patients in whom low cardiac output rather than elevated pulmonary pressure is the primary hemodynamic aberration. However, milrinone reduces left atrial congestion more effectively than dobutamine, and is well tolerated and effective when used in patients receiving β-blockers. In-patient therapy for decompensated HF is a short term exercise for symptom relief and provides an opportunity to re-assess management in the continuum of care.     

Chronic Heart Failure

Heart failure (HF) is a complex syndrome characterized by the inability of the heart to maintain a normal cardiac output without elevated intracardiac filling pressures, resulting in signs of pulmonary and peripheral edema and symptoms of dyspnea and fatigue. Central to the management of HF is a multifaceted pharmacological intervention to abate the harmful counter-regulatory effects of neurohormonal activation and avid salt and water retention. Whereas up to 40 years ago HF was managed with diuretics and leaf of digitalis, the cornerstones of therapy for HF patients with systolic dysfunction now include ACE inhibitors or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers), β-adrenoceptor antagonists (β-blockers), and aldosterone antagonists, which have significantly improved survival. However, with the increasing number of beneficial therapies, there are challenges to implementing all of them. Specific cardiomyopathies also merit specific considerations with respect to treatment, and — unfortunately — there is no therapy for HF with preserved left ventricular ejection fraction that has been shown to improve survival. Although mortality has improved in HF, the biggest challenge to treatment lies in addressing the morbidity of this disease, which is now the most common reason for hospital admission in our aged population. As such, there are many therapies that may serve to improve the quality of life of HF patients. Future HF treatment regimens may include direct cellular therapy via hormone and cytokine signaling or cardiac regeneration through growth factors or cell therapy.     

LCZ696 开启射血分数减低心力衰竭患者治疗的新时代：来自PARADIGM-HF 的证据

心力衰竭（心衰）是由于任何心脏结构或功能异常导致心室充盈或射血能力受损的一组复杂临床综合征,其发病率、病死率高。肾素-血管紧张素-醛固酮系统（RAAS）的长期激活在心衰发生发展的病理生理学机制中发挥着重要作用。血管紧张素转换酶抑制剂（ACEI）、血管紧张素受体拮抗剂（ARB）以及醛固酮受体拮抗剂（MRA）已经被大规模临床试验证实对心衰具有良好的治疗效果,在心衰药物治疗策略中处于重要地位。2014 年8 月30 日在欧洲心脏病学会年会首次公布PARADIM-HF 的研究结果显示,在患者已经使用了β受体阻滞剂和MRA 基础之上, LCZ696 使心血管病死亡风险降低了20%,慢性心衰患者因心衰而住院的次数减少了21%。LCZ696 以其独特的双相作用模式,再次证实调节神经内分泌是治疗心衰的现代观念。LCZ696 将带来传统心衰药物治疗的革新。心衰治疗将大跨步进入一个新时代。     

护理干预对慢性心力衰竭患者临床疗效的影响

目的探讨慢性心力衰竭患者的护理干预方法及其对心功能和预后的影响。方法选择慢性心力衰竭患者80例随机分为干预组40例和对照组40例。对照组采用慢性心力衰竭的常规药物治疗;干预组在对照组的治疗基础上接受专业护理人员的护理干预。随访1年,观察2组患者的1年病死率、再住院人次及心功能指标。结果干预组左心室射血分数均高于对照组,心功能NYHA分级、再住院人次及左心室舒张末期内径均低于对照组,差异均有统计学意义（P〈0.05）。干预组病死率低于对照组,但差异无统计学意义（P〉0.05）。结论对慢性心力衰竭患者进行合理的护理干预可改善患者心功能及临床预后。     

改善心力衰竭能量代谢的潜在药物研究进展

心力衰竭（HF）是一个全球性的公共卫生问题,发病率和死亡率都很高。研究表明,HF是由严重的能量代谢紊乱引起的,导致心脏能量供应不足。这种能量缺乏会导致心脏泵血功能障碍和全身其他器官能量代谢的衰竭。针对HF的疗法主要通过降低心率和心脏前负荷和后负荷、对症治疗或延缓疾病的发展来发挥作用。然而,针对心脏能量代谢的药物却尚未研发出来。本文概述健康心脏中能量代谢的主要特征、HF期间的代谢变化,并讨论通过能量代谢来改善心脏功能的药物,为治疗HF药物的研发和应用提供新的研究方向。     

GRK2 inhibition in heart failure: something old, something new

Despite significant advances in pharmacological and clinical treatment, heart failure (HF) remains the number one killer disease in the western world. HF is a chronic and progressive clinical syndrome mainly characterized by reduction in left ventricular ejection fraction and adverse remodeling of the myocardium. One of its hallmark molecular abnormalities is elevation of cardiac G protein-coupled receptor (GPCR) kinase (GRK)-2, originally termed beta-adrenergic receptor kinase-1 (βARK1), a member of the GRK family of serine/threonine protein kinases which phosphorylate and desensitize GPCRs. Up-regulated GRK2 in the heart underlies the diminished contractile responsiveness of the heart to positive inotropes, as it abrogates the pro-contractile signaling of various important cardiac receptors: mainly β-adrenergic receptors (βARs), but also angiotensin II type 1 receptors (AT(1)Rs), etc. Thus, cardiac-specific GRK2 inhibition via various transgenic approaches is postulated to combat chronic HF symptoms by increasing cardiac function, and even be salutary in some cases by increasing survival. This has been extensively documented over the past 15 years through a vast series of preclinical studies on animals of all sizes and shapes, from small mice up to large rabbits and pigs closely resembling human physiology, and genetically manipulated to have cardiac GRK2 inhibited or deleted, transiently or permanently. However, over the past several years, it has become increasingly clear that GRK2, like other members of the GRK family, exerts additional effects that can aggravate HF, in addition to merely blunt cardiac contractility by opposing cardiac βAR G protein-mediated signaling. One of these newly discovered cardiotoxic effects of GRK2, uncovered by our laboratory, is promotion by adrenal GRK2 of sympathetic hyperactivity of the failing heart, a significant morbidity factor in HF, targeted therapeutically nowadays by the use of beta-blockers in HF pharmacotherapy. Thus, new avenues for therapeutic exploitation of GRK2 inhibition in HF treatment might be possible in the near future. The present review gives first a brief account of what has already been documented about the benefits of cardiac GRK2 genetic manipulation in HF as a positive inotropic therapy for the disease, and then goes on to discuss in detail the intriguing new possibility that has emerged of lowering GRK2 activity in the adrenal gland, which could constitute a novel sympatholytic therapy for HF that helps relieve the devastatingly cardiotoxic sympathetic overload of the failing heart.     

Safety of antidepressant drugs in the patient with cardiac disease: a review of the literature

Patients with cardiac disease, specifically ischemic heart disease and heart failure, have a higher frequency of major depressive disorder than patients without cardiac disease. The pathophysiologic reason for this is not completely understood. Previous depression, other debilitating illnesses, and type A personality are risk factors for the development of depression in cardiac patients. Depression has been shown to lower the threshold for ventricular arrhythmias. Therefore, treatment of depression potentially may prolong life in these patients. Antidepressant options that have been evaluated include several of the tricyclic antidepressants, trazodone, bupropion, and several of the selective serotonin reuptake inhibitors. Individual antidepressant drugs vary in their pharmacologic activity and side-effect profiles. Although clinical data are limited, it is important to individualize therapy in order to minimize cardiac adverse effects. Clinicians are encouraged to evaluate patients with cardiac disease for major depressive disorder and to consider antidepressant drug therapy for these patients when appropriate.     

Left ventricular hypertrophy: a shift in paradigm

Observational studies have identified left ventricular hypertrophy (LVH) as a strong, independent risk factor for the development of heart failure (HF), coronary heart disease and stroke. LVH develops in response to hemodynamic overload. Classical conceptualization has it that LVH would start as an adaptive, beneficial response in order to normalize wall stress. With progression of the disease, deterioration to maladaptive hypertrophy, and further on to HF could occur. Recent experiments in animal models of pressure-overload and myocardial infarction now challenge this concept by demonstrating that blunting the hypertrophic response is actually associated with preserved cardiac function, and with improved survival. These findings may have profound therapeutical implications.     

Indications for heart transplantation in current era of left ventricular assist devices

Although both heart transplantation and left ventricular assist device therapy have enjoyed clinical success in the treatment of patients with end-stage heart disease, newer left ventricular assist devices currently undergoing testing are likely to have a tremendous impact on the management of these patients. Smaller, more durable devices with improved safety profiles will allow for longer duration of therapy and make biventricular support more feasible, obviating the need for the total artificial heart. In this article we review the historical aspects of both forms of therapy and highlight the current use of left ventricular assist device therapy on patients awaiting heart transplantation.     

Safe and Effective Use of Pharmacologic and Device Therapy for Peripartum Cardiomyopathy

Peripartum cardiomyopathy (PPCM) is an uncommon, idiopathic complication of pregnancy associated with significant (10–30%) mortality. The disease occurs late in pregnancy or in the months following delivery, resulting in reduced systolic function and heart failure (HF) symptoms. Limited direction is provided for the management of PPCM, and the safe and effective use of medications in pregnant and breastfeeding women with PPCM presents a unique challenge. Although several HF therapies in pregnant and lactating women are supported by robust evidence, evidence to support the use of other therapies is significantly lacking. Current guidelines recommend treatment as in other forms of HF with reduced left ventricular ejection fraction (LVEF) but with consideration for the important nuances in this population as well as the unique and potential teratogenic effects of these therapies. Since most patients with PPCM recover their LVEF, the duration of therapy is currently unknown and warrants further study. We review the available literature surrounding pharmacologic and device therapy for PPCM and provide insight into managing patients with the condition.     

Beta-Blockers and Ivabradine in Chronic Heart Failure: From Clinical Trials to Clinical Practice

Beta-blockers have become one of the cornerstones of treatment of patients with heart failure (HF) and depressed left ventricular function, but in clinical practice only 30–35 % of patients achieve the therapeutic target dose as established in randomized clinical trials. Moreover, high resting heart rate (HR) has emerged as a simple but relevant risk factor for cardiovascular events, including coronary artery disease and HF; also, it was found to have an independent prognostic value in patients with HF. Evidence that HR could be considered a good parameter to evaluate the quality of treatment in patients with HF has been suggested; of note, many patients maintain a resting HR ≥70 beats per minute despite optimal beta-blocker therapy. In recent years, a new drug able to reduce HR, ivabradine, has been introduced in clinical practice, and its use in the clinical setting of HF patients has been recommended by current European Society of Cardiology (ESC) guidelines. Here we review the evidence of the prognostic role of HR in systolic HF and the potential relationship between HR lowering and the beneficial effects of beta-blockers; we will also analyze the reasons why an appropriate use of these drugs is seldom achieved in clinical practice, and review the evidence for the use of ivabradine in systolic HF in the clinical setting.     

血浆脑利钠肽与心力衰竭关系的临床研究

目的探讨血浆脑利钠肽（BNP）在心力衰竭患者体内的变化规律以及对心功能评估的价值。方法用免疫荧光法测定110例心力衰竭患者（HF组）及20例健康体检者（对照组）血浆BNP浓度;行超声心动图仪检查测定左室射血分数（LVEF）。结果HF组BNP值明显高于对照组,差异有统计学意义（P〈0.01）,且HF组随NYHA分级增高其BNP水平越高;心功能Ⅰ级,Ⅱ级,Ⅲ级、Ⅳ级比较,BNP水平差异均有统计学意义（P〈0.01）;治疗后1周BNP值同治疗前有显著降低（P〈0.01）;LVEF与BNP水平成负相关,血浆BNP水平较高者病死率增加。结论监测BNP水平可作为心力衰竭诊断、心功能评估以及疗效及预后的指导指标。     

Therapeutic developments in sudden cardiac death

Sudden cardiac death is characterised by the unexpected death of a patient who has been clinically stable. It is frequently due to the development of ventricular tachyarrhythmias. With appropriate treatment, patients can be appropriately resuscitated. Clinically, it is essential to develop treatment strategies to prevent such an episode, as most patients do not survive out-of-hospital cardiac arrest. beta-Blockers are an effective pharmacological therapy in patients following myocardial infarction and in those with congestive heart failure. They may also be effective in other types of heart disease. Anti-arrhythmic agents are not useful as prophylactic drug therapy for reducing mortality in patients at risk for sudden cardiac death. Amiodarone is a notable exception, which may have some benefit, particularly in some subgroups. The implantable cardioverter-defibrillator has emerged as the most effective therapy for preventing sudden cardiac death in high-risk patients. Further work is required to enhance the characterisation of high-risk patients. Genetic analyses in patients with cardiovascular disorders may also identify new approaches to the prevention of sudden cardiac death.     

Therapeutic developments in sudden cardiac death

Sudden cardiac death is characterised by the unexpected death of a patient who has been clinically stable. It is frequently due to the development of ventricular tachyarrhythmias. With appropriate treatment, patients can be appropriately resuscitated. Clinically, it is essential to develop treatment strategies to prevent such an episode, as most patients do not survive out-of-hospital cardiac arrest. β-Blockers are an effective pharmacological therapy in patients following myocardial infarction and in those with congestive heart failure. They may also be effective in other types of heart disease. Anti-arrhythmic agents are not useful as prophylactic drug therapy for reducing mortality in patients at risk for sudden cardiac death. Amiodarone is a notable exception, which may have some benefit, particularly in some subgroups. The implantable cardioverter-defibrillator has emerged as the most effective therapy for preventing sudden cardiac death in high-risk patients. Further work is required to enhance the characterisation of high-risk patients. Genetic analyses in patients with cardiovascular disorders may also identify new approaches to the prevention of sudden cardiac death.