Treatment options in end-stage heart failure: where to go from here?

Chronic heart failure is a major healthcare problem associated with high morbidity and mortality. Despite significant progress in treatment strategies, the prognosis of heart failure patients remains poor. The golden standard treatment for heart failure is heart transplantation after failure of medical therapy, surgery and/or cardiac resynchronisation therapy. In order to improve patients' outcome and quality of life, new emerging treatment modalities are currently being investigated, including mechanical cardiac support devices, of which the left ventricular assist device is the most promising treatment option. Structured care for heart failure patients according to the most recent international heart failure guidelines may further contribute to optimal decision-making. This article will review the conventional and novel treatment modalities of heart failure.     

Compression entropy contributes to risk stratification in patients with cardiomyopathy.

Sudden cardiac death (SCD) is a leading cause of mortality with an incidence of 3 million cases per year worldwide. Therapies for patients who have survived an SCD episode or have a high risk of developing lethal ventricular arrhythmia are well established and depend mainly on risk stratification. In this study we investigated the suitability of the non-linear measure compression entropy (Hc) for improved risk prediction in cardiac patients. We recorded 24-h Holter ECG for 300 patients with congestive heart failure (CHF). During a mean follow-up period of 12 months, 32 patients died due to a cardiac event. Hc depends on the compression parameters window length w and buffer length b, which were optimised by analysing a subgroup of patients. Compression entropies based on the beat-to-beat interval (BBI) were subsequently calculated and compared with standard heartrate variability parameters. Statistical analysis revealed significant differences between high- and low-risk CHF patients in standard HRV measures, as well as compression entropy based on the BBI (cardiac death, p = 0.005; SCD, p = 0.02). In conclusion, the implementation of non-linear compression entropy analysis in multivariate analysis seems to be useful for enhanced risk stratification of cardiac death, especially SCD, in ischaemic cardiomyopathy patients.     

Rubella Syndrome—Cardiovascular Manifestations and Surgical Therapy in Infants

Of nine patients under five months of age with cardiovascular manifestations of the rubella syndrome, six had patent ductus arteriosus. Three of these six also had pulmonary artery stenosis. One infant had bilateral isolated pulmonary artery stenosis. The significant clinical findings leading to the diagnosis of pulmonary artery stenosis were axillary murmurs in the presence of right ventricular hypertrophy. Demonstration of a gradient across the stenosis at the time of catheterization, together with cineangiography, established the diagnosis. In two cases ventricular septal defect was the only cardiac anomaly.Six babies under five months of age had interruption of a patent ductus arteriosus because of uncontrollable congestive heart failure or failure to thrive. Although growth failure was not necessarily due to heart disease, all were developing satisfactorily following operation.Diagnosis and therapy of the cardiac complications of the rubella syndrome is possible in the first few months of life. Early recognition of cardiac defects in the young infant with the rubella syndrome permits aggressive medical management and in selected instances surgical therapy.     

Effect of erythropoietin in a patient with severe congestive heart failure--a case report

Erythropoietin (EPO), traditionally known as a hematopoietic hormone, has recently been shown to have effects beyond hematopoiesis such as prevention of neuronal and cardiac apoptosis secondary to ischemia and induction of neoangiogenesis. Patients with congestive heart failure (CHF) suffer considerable morbidity and mortality despite advances in therapy. Anemia, CHF, and chronic kidney insuficiency often coexist and interact to cause or worsen each other in the so-called cardio-renal anemia syndrome. Treatment with EPO has shown promise in such patients. The paper reviews a case of a successful recovery of cardiac function in a patient with a severe CHF during the treatment with EPO.     

肾脏去神经化在心力衰竭治疗中的研究进展

生理情况下,心脏和肾脏在血流动力学和神经激素等调节中相互作用,对于循环系统的稳态维持起重要作用。但在充血性心力衰竭的病理情况下,心脏和肾脏之间存在明显的调节紊乱。首先,急性失代偿性心力衰竭的患者住院治疗的研究结果证明其有一定程度的肾脏失调。其次,慢性充血性心力衰竭时肾脏交感神经系统也起到重要作用:肾脏交感纤维活性增强可导致肾素的释放、钠水潴留、肾血流的降低、血管阻力增加、左心室重塑、左心功能失调等。众所周知,肾脏交感神经切除术可以减低血压和改善心脏功能,但是由于有创的手术方式限制了其应用。过去两年间,随着新的导管消融肾脏去神经化技术的日益完善,其有望成为治疗高血压病和心力衰竭的手段。在此,本文综述了心力衰竭时肾脏交感传入神经和传出神经的发病机理,对目前进行的经导管肾脏去神经化治疗慢性心力衰竭的基础及临床试验进行安全性及有效性评价。提示我们经导管肾脏去神经化有望成为心力衰竭治疗的新靶点。     

Importance of antioxidant and antiapoptotic effects of beta-receptor blockers in heart failure therapy

The present study was carried out to determine whether beneficial effects of carvedilol in congestive heart failure (CHF) are mediated via its beta-adrenergic blocking, antioxidant, and/or alpha-adrenergic blocking action. Rabbits with heart failure induced by rapid cardiac pacing were randomized to receive subcutaneous carvedilol, metoprolol, propranolol plus doxazosin, or placebo pellets for 8 wk and compared with sham-operated rabbits without pacing. We found rapid cardiac pacing produced clinical heart failure, left ventricular dilation, and decline of left ventricular fractional shortening. This was associated with an increase in left ventricular end-diastolic pressure, decrease in left ventricular first derivative of left ventricular pressure, and myocyte hypertrophy. Tissue oxidative stress measured by GSH/GSSG was increased in the heart with increased oxidation product of mitochondrial DNA, 8-oxo-7,8-dihydro-2'-deoxyguanosine, increase of Bax, decrease of Bcl-2, and increase of apoptotic myocytes as measured by anti-single-stranded DNA monoclonal antibody. Administration of carvedilol and metoprolol, which had no effect in sham animals, attenuated cardiac ventricular remodeling, cardiac hypertrophy, oxidative stress, and myocyte apoptosis in CHF. In contrast, propranolol plus doxazosin, which has less antioxidant effects, produced smaller effects on left ventricular function and myocyte apoptosis. In all animals, GSH/GSSG correlated significantly with changes of left ventricular end-diastolic dimension (r = -0.678, P < 0.0001), fractional shortening (r = 0.706, P < 0.0001), and apoptotic myocytes (r = -0.473, P = 0.0001). Thus our findings suggest antioxidant and antiapoptotic actions of carvedilol and metoprolol are important determinants of clinical beneficial effects of beta-receptors in the treatment of CHF.     

促红细胞生成素治疗慢性心力衰竭156例临床观察

目的:观察EPO对慢性充血性心力衰竭(CHF)治疗效果。方法:选择CHF患者212例,随机分为非EPO治疗组(56例)和EPO治疗组(156例)。其中非EPO治疗组采用常规抗心衰治疗,EPO治疗组接受常规抗心衰治疗和EPO治疗,直至临床观察结束。治疗后观察心功能指标改变。结果:156例心衰患者经过EPO治疗后,左室射血分数,每搏输出量,每分输出量,心指数均较非EPO治疗对照组患者明显改善(P<0.05),其中尤以左室射血分数改善最为明显(P<0.01)。156例EPO治疗组患者中116例心衰伴贫血患者心功能各项指标的改善较40例心衰不伴贫血患者更为明显,具有显著统计学意义(P<0.01)。结论:EPO对CHF患者心功能的改善主要是因为EPO的促红细胞生成作用。EPO对于慢性心功能不全有独立于促红细胞生成以外的治疗作用。     

New information about resynchronisation

Chronic atrio-biventricular pacing appears to become a very attractive and promising additive therapy for congestive heart failure with systolic left ventricular impairment. The best results can only be achieved by an optimal interaction between the cardiologists involved. Until now no sort of cardiac intervention has ever required such close and ongoing cooperation to serve the cardiac patient. These efforts are welcomed because congestive heart failure strongly reduces the quality of mental health and physical functioning.By means of questions and answers on new information about cardiac resynchronisation, this special article aims to provide more insight into the role of this complex pacing therapy.     

Contralateral transvenous left ventricular lead placement of implantable devices with pre-sternal tunnelling in chronically obstructed subclavian veins

Cardiac resynchronisation therapy (CRT) is a recognised therapy for the management of severe left ventricular dysfunction, advanced congestive cardiac failure (NYHA III or IV), ventricular dyssynchrony (either broad LBBB or mechanical dyssynchrony on echocardiography) and failure of optimal medical therapy to achieve improvement in clinical status. Upgrading right ventricular pacemakers or defibrillators to biventricular devices is common and we describe here, 2 such cases of biventricular upgrade with blocked venous access on the ipsilateral side and successful placement of left ventricular leads following pre-sternal tunnelling from the contralateral side.     

左旋卡尼汀联合环磷腺苷葡胺治疗慢性充血性心力衰竭

目的:探究左旋卡尼汀联合环磷腺苷葡胺治疗慢性充血性心力衰竭(chronic congestive heart failure,CHF)的临床疗效。方法:选取我院心内科CHF患者58例,随机分为对照组28例与实验组30例,其中对照组28例,予地高辛、氢氯噻嗪、环磷腺苷葡胺常规治疗;实验组30例,在常规治疗的基础上加用左旋卡尼汀治疗。观察两组患者治疗前后心功能分级(NYHA)、6 min步行距离、左心室射血分数(LVEF)及左心室舒张末容积(LVEDD)等。结果:与对照组比较,实验组患者治疗后心率和NYHA心功能分级明显改善,6 min步行实验明显提高,患者LVEDD、LVEF明显改善,差异具有统计学意义(P<0.05);两组患者接受相应治疗后均未出现任何不良反应(P>0.05)。结论:左旋卡尼汀联合环磷腺苷葡胺能够明显改善慢性充血性心力衰竭,对临床具有指导意义,值得临床推广。     

Regulation of cardiac adrenomedullin in heart failure.

Adrenomedullin (ADM), a potent natriuretic and vasorelaxing peptide with inotropic properties, is elevated in plasma in human and experimental congestive heart failure (CHF). Recent studies suggest that angiotensin II stimulates ADM production and secretion from cardiac myocytes and fibroblasts. In the present study, we investigated cardiac ADM in experimental CHF, and tested the hypothesis that angiotensin converting enzyme (ACE) inhibition modulates cardiac ADM in CHF. Cardiac tissue ADM immunoreactivity and gene expression were assessed by radioimmunoassay, immunohistochemistry, in situ hybridization and Northern blot analysis in normal and CHF dogs in the presence and absence of ACE inhibition. Experimental CHF was produced by progressive rapid ventricular pacing and characterized by increased ventricular ADM concentrations as well as increased ventricular ADM gene expression. ACE inhibition abolished the increases in ventricular ADM concentrations and ventricular ADM gene expression in CHF. Ventricular ADM gene expression was localized to ventricular myocytes and correlated with left ventricular mass index, suggesting that ventricular ADM is a marker for ventricular hypertrophy. In contrast, atrial ADM concentrations and gene expression did not change in CHF with or without ACE inhibition. Increased plasma ADM concentrations in CHF were also abolished with ACE inhibition. The present study demonstrates that circulating and ventricular ADM are activated in pacing-induced experimental CHF and that ACE inhibition reverses ventricular ADM activation in CHF. This study also indicates that cardiac ADM gene expression is differently regulated between atrium and ventricle in CHF.     

Ventricular cardiotrophin-1 activation precedes BNP in experimental heart failure

Both cardiotrophin-1 (CT-1) and B-type or brain natriuretic peptide (BNP) are activated by cardiomyocyte stretch, and gene expression of CT-1 and BNP are augmented in the heart in experimental and human congestive heart failure (CHF). The goal of this study was to define cardiac gene expression of CT-1 and BNP by Northern blot analysis in normal (n=5), early left ventricular dysfunction (ELVD, n=5) and overt CHF dogs (n=5), in which ventricular function is progressively decreased. CT-1 mRNA was detected in both atria and ventricles in normal dogs. Ventricular CT-1 mRNA production increased in ELVD, and it further increased in overt CHF. Ventricular BNP mRNA remained below or at the limit of detection in normal and ELVD models, and it markedly increased in overt CHF. This study reports differential regulation of gene expression of CT-1 and BNP in the heart during the progression of CHF, and demonstrates that ventricular CT-1 gene activation precedes ventricular BNP gene activation.     

Arrhythmogenic risks of stem cell replacement therapy for cardiovascular diseases

Ischemic heart disease and congestive heart failure are major contributors to high morbidity and mortality. Approximately 1.5 million cases of myocardial infarction occur annually in the United States; the yearly incidence rate is approximately 600 cases per 100,000 people. Although significant progress to improve the survival rate has been made by medications and implantable medical devices, damaged cardiomyocytes are unable to be recovered by current treatment strategies. After almost two decades of research, stem cell therapy has become a very promising approach to generate new cardiomyocytes and enhance the function of the heart. Along with clinical trials with stem cells conducted in cardiac regeneration, concerns regarding safety and potential risks have emerged. One of the contentious issues is the electrical dysfunctions of cardiomyocytes and cardiac arrhythmia after stem cell therapy. In this review, we focus on the cell sources currently used for stem cell therapy and discuss related arrhythmogenic risk.     

Current clinical perspectives on myocardial angiogenesis

Currently accepted modalities of treatment for atherosclerotic coronary artery disease (CAD) include pharmacological therapy, and revascularization with either bypass surgery or percutaneous coronary intervention (PCI). Similarly, conventional treatment of congestive heart failure (HF) is limited to medical therapy, temporary assist devices and in a select few, cardiac transplantation. A significant subset of patients with severe symptomatic CAD and end stage HF is not eligible for these traditional methods of treatment. In spite of maximal medical and revascularization therapy, these patients may not get adequate symptomatic relief. After a decade of investigations, gene therapy is emerging as a promising therapeutic option for this group of patients. This review discusses myocardial angiogenesis as a therapeutic modality in these patients including therapeutic angiogenesis with growth factors and cell transplantation.     

Sodium channel enhancer restores baroreflex sensitivity in conscious dogs with heart failure

We compared the cardiac inotropic, lusitropic, and chronotropic responses to the Na(+) channel enhancer LY-368052 in conscious dogs before and after development of congestive heart failure (CHF). We also examined the effect of LY-368052 on baroreflex sensitivity and the efferent neural mechanisms of the bradycardic response in heart failure. Dogs were chronically instrumented, and heart failure was induced by right ventricular pacing at 240 beats/min for 3-4 wk. LY-368052 dose-dependently increased left ventricular contractile performance before and after the development of CHF to a similar extent. The inotropic effect of LY-368052 in heart failure was not altered by either ganglionic or beta-adrenergic receptor blockade. LY-368052 improved cardiac relaxation and induced bradycardia in dogs with heart failure but not in normal dogs. The negative chronotropic effect of LY-368052 was eliminated by ganglionic blockade but not beta-adrenergic blockade, suggesting that the bradycardia was mediated by the autonomic nervous system via enhanced parasympathetic tone. Baroreflex sensitivity was assessed as the pulse interval-mean arterial pressure slope in response to temporary pharmacological (nitroglycerin or phenylephrine) and mechanical (brief occlusion of inferior vena cava) alterations of arterial pressure in conscious dogs before and after development of heart failure. Baroreflex sensitivity was significantly depressed in heart failure and restored completely by acute treatment with LY-368052. Thus the Na(+) channel enhancer LY-368052 maintains its beta-receptor-independent inotropic effect in chronic CHF and specifically improves ventricular relaxation and depressed baroreflex function.     

Adriamycin (Doxorubicin) Cardiotoxicity: A Review

Adriamycin (doxorubicin hydrochloride) is an antineoplastic agent effective against a wide range of malignant conditions, although cardiac toxicity, especially dose-dependent cardiomyopathy, limits its long-term use. Previous mediastinal radiation therapy or left ventricular dysfunction and advanced age increase the risk of this complication developing. Unfortunately, there is no readily available, noninvasive method that can predict Adriamycin-induced congestive heart failure (CHF). However, both endomyocardial biopsy and radionuclide ejection-fraction measurement are promising techniques which may soon permit selection of patients who can safely receive this drug. At present, Adriamycin-induced CHF can best be prevented by limiting the total dose as follows: 400 to 450 mg per sq meter following mediastinal radiation and 500 to 550 mg per sq meter for patients without other significant risk factors. Consideration of dose-response data and use of a weekly schedule may soon permit the administration of Adriamycin for long-term antineoplasm therapy.     

Role of echocardiography in diagnosis and risk stratification in heart failure with left ventricular systolic dysfunction

Congestive heart failure with preserved left ventricular systolic function has emerged as a growing epidemic medical syndrome in developed countries, which is characterized by high morbidity and mortality rates. Rapid and accurate diagnosis of this condition is essential for optimizing the therapeutic management. The diagnosis of congestive heart failure is challenging in patients presenting without obvious left ventricular systolic dysfunction and additional diagnostic information is most commonly required in this setting. Comprehensive Doppler echocardiography is the single most useful diagnostic test recommended by the ESC and ACC/AHA guidelines for assessing left ventricular ejection fraction and cardiac abnormalities in patients with suspected congestive heart failure, and non-invasively determined basal or exercise-induced pulmonary capillary hypertension is likely to become a hallmark of congestive heart failure in symptomatic patients with preserved left ventricular systolic function. The present review will focus on the current clinical applications of spectral tissue Doppler echocardiography used as a reliable noninvasive surrogate for left ventricular diastolic pressures at rest as well as during exercise in the diagnosis of heart failure with preserved left ventricular systolic function. Chronic congestive heart failure, a disease of exercise, and acute heart failure syndromes are characterized by specific pathophysiologic and diagnostic issues, and these two clinical presentations will be discussed separately.     

Stem cell engineering for treatment of heart diseases: Potentials and challenges

Heart disorders are a major health concern worldwide responsible for millions of deaths every year. Among the many disorders of the heart, myocardial infarction, which can lead to the development of congestive heart failure, arrhythmias, or even death, has the most severe social and economic ramifications. Lack of sufficient available donor hearts for heart transplantation, the only currently viable treatment for heart failure other than medical management options (ACE inhibition, beta blockade, use of AICDs, etc.) that improve the survival of patients with heart failure emphasises the need for alternative therapies. One promising alternative replaces cardiac muscle damaged by myocardial infarction with new contractile cardiomyocytes and vessels obtained through stem cell-based regeneration.We report on the state of the art of recovery of cardiac functions by using stem cell engineering. Current research focuses on (a) inducing stem cells into becoming cardiac cells before or after injection into a host, (b) growing replacement heart tissue in vitro, and (c) stimulating the proliferation of the post-mitotic cardiomyocytes in situ. The most promising treatment option for patients is the engineering of new heart tissue that can be implanted into damaged areas. Engineering of cardiac tissue currently employs the use of co-culture of stem cells with scaffold microenvironments engineered to improve tissue survival and enhance differentiation. Growth of heart tissue in vitro using scaffolds, soluble collagen, and cell sheets has unique advantages. To compensate for the loss of ventricular mass and contractility of the injured cardiomyocytes, different stem cell populations have been extensively studied as potential sources of new cells to ameliorate the injured myocardium and eventually restore cardiac function. Unresolved issues including insufficient cell generation survival, growth, and differentiation have led to mixed results in preclinical and clinical studies. Addressing these limitations should ensure the successful production of replacement heart tissue to benefit cardiac patients.     

Circadian mesor of recumbent pulse--cost-effective predictor of doxorubicin-induced congestive heart failure

Nineteen adult cancer patients each received 6-10 monthly treatments of doxorubicin and cisplatin. For 24-30 hr before each treatment, recumbent pulse was measured. Treatment was stopped for disease progression or when a total doxorubicin dose of 550 mg/m2 was reached. No patient developed congestive heart failure (CHF) during therapy. Two to four months after stopping treatment, three patients developed CHF. In these cases, 2-6 months before complication of therapy, prior to notable decrement in any other index of cardiac function, the 24-hr rhythm-qualified mean (mesor) of pulse showed a positive slope by linear regression analysis (P less than 0.05). This mesor rise was apparent at cumulative doxorubicin doses of 300, 420 and 240 mg/m2. patients subsequently received additional doxorubicin to total doses of 540, 525 and 530 mg/m2. Patients who did or did not experience a rise in pulse received similar total doses of doxorubicin. Serial pulse mesors predicted CHF reliably and were substantially less expensive than radionuclide ejection fraction determination ($200 per test). A progressive rise in the circadian pulse-mesor was clearly a harbinger of histologically documented doxorubicin-induced lethal CHF in Wistar-Kyoto rats of both sexes.