Reversing chronic remodeling in heart failure

Chronic heart failure is a debilitating condition with significant morbidity, mortality and an increasing economic burden. The past 20 years have witnessed great strides in both medical and device-based therapies for heart failure. Central to these developments has been the ability to favorably reverse the chronic processes by which the failing heart remodels. In addition to pharmacotherapies, such as β-blockade, and inhibition of the renin–angiotensin–aldosterone system, surgical remodeling, containment devices and new methods to restore synchronous contraction have been added to the armamentarium, in some instances, providing clear improvement to both symptoms and mortality. In more advanced stages of heart failure, left ventricular-assist devices provide marked unloading of the failing ventricle and such therapy has provided unique insights into the molecular and cellular mechanisms underlying reverse remodeling, given the immediate access to cardiac tissue. Genetic and cellular approaches, as well as new small molecule targets, may provide future avenues for reverse remodeling of the failing heart, improving symptoms and disease outcome.     

Cardiac remodeling in chronic heart failure

Left ventricular remodeling plays an important role in the progression of chronic heart failure. The early remodeling is an adaptive response to the increased load(i.e. hypertension) and/or the loss of contractile component (i. e. myocardial infarction) in order to maintain the pumping capacity. This process includes cardiac hypertrophy associated with myocyte hypertrophy and myocardial fibrosis. However, the persistence of the inadequate overload results in the decompensation of the adaptive mechanism. Finally, left ventricle is enlarged and the systolic function is impaired.     

Reversing chronic remodeling in heart failure

Chronic heart failure is a debilitating condition with significant morbidity, mortality and an increasing economic burden. The past 20 years have witnessed great strides in both medical and device-based therapies for heart failure. Central to these developments has been the ability to favorably reverse the chronic processes by which the failing heart remodels. In addition to pharmacotherapies, such as beta-blockade, and inhibition of the renin-angiotensin-aldosterone system, surgical remodeling, containment devices and new methods to restore synchronous contraction have been added to the armamentarium, in some instances, providing clear improvement to both symptoms and mortality. In more advanced stages of heart failure, left ventricular-assist devices provide marked unloading of the failing ventricle and such therapy has provided unique insights into the molecular and cellular mechanisms underlying reverse remodeling, given the immediate access to cardiac tissue. Genetic and cellular approaches, as well as new small molecule targets, may provide future avenues for reverse remodeling of the failing heart, improving symptoms and disease outcome.     

应用心衰超声指数评价慢性心力衰竭患者的临床价值

目的:采用综合超声心动图多项参数的心衰超声指数评价慢性心力衰竭患者的心功能状态,旨在为临床提供更为全面、客观和量化的指标.方法:前瞻性研究慢性心力衰竭患者116例(心衰组),正常者24例(时照组),所有入选者进行心衰超声指数的评分,并将该评分与同期血浆氨基末端脑钠肽前体(NT-ProBNP)水平及纽约心功能分级(NYHA)进行比较,同时评价其诊断慢性心力衰竭的敏感性与特异性.结果:(1)心衰超声指数值在心衰组明显大于对照组.当心衰超声指数值大于≥3时,其诊断慢性有症状性心力衰竭的敏感性、特异性、阳性预测值、阴性预测值分别为88.6%、91.4%、96.8%及80.0%.(2)相关性分析表明心衰超声指数值与Log NT-ProBNP水平呈明显正相关(r=0.86,P<0.01).(3)NYHA Ⅰ、Ⅱ、Ⅲ、Ⅳ级患者的心衰超声指数值分别为1.80±0.80、3.66±1.49、4.96±2.09和6.07±1.78,方差分析显示组间差异均有显著性(P<0.01).结论:应用心衰超声指数来诊断慢性心衰及客观评价其严重程度是可行的,心衰超声指数作为综合评价慢性心衰患者心功能状态的一个新指标值得在临床推广应用.     

Isolated ultrafiltration in treating chronic heart failure

Twenty-five patients with chronic heart failure resistant to drug therapy were subjected to isolated ultrafiltration (IUF) as part of the complex of therapeutic measures. Altogether 76 IUF sessions were made. The results of the use of IUF were controlled by the clinical observation, laboratory studies and ultrasonic exploration of the internal organs. It has been shown that IUF should be included into the complex of therapeutic measures for chronic heart failure.     

Losartan in therapy of chronic heart failure

To evaluate effectiveness of nonpeptide angiotensin-2 subtype-1 receptor antagonist losartan in therapy of symptomatic congestive heart failure in patients with ischemic heart disease, 116 patients were examined at the age of 36-62 (mean age 50.6 +/- 4.22). They had angina pectoris of functional class II-III (according to CCS) and congestive heart failure of functional class II-III (according to NYHA). All the patients were randomized into two groups. 60 patients of group 1 received basic medication with nitrates, diuretic (on demand), digoxin and aspirin. 56 patients of group 2 received basic medication and losartan (cozaar, MSD, USA) in the dose 25 mg/day for 48 weeks. Echocardiographic monitoring of the treatment efficacy was made. The outcomes of the treatment evidence that losartan improves the patients' clinical status and heart failure functional class. For twelve weeks losartan reduced left ventricular and atrial dilation positively influencing the isometric inotropic indices. In 48 weeks losartan arrested progression of pathologic remodelling of the left ventricle and prevents depression of total myocardial contractility. Losartan's positive effect in restriction of negative evolution of cardiac failure manifests on the treatment week 3.     

Extended-release metoprolol succinate in chronic heart failure

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and tolerability of extended-release (ER) metoprolol succinate and its role in the management of chronic heart failure. DATA SOURCES: A MEDLINE search of English-language literature (1990-October 2002) was conducted using congestive heart failure and metoprolol CR/XL or metoprolol CR/ZOK as search terms to identify pertinent studies. STUDY SELECTION/DATA EXTRACTION: All of the articles identified from the data sources were evaluated, with priority given to randomized, double-blind, placebo-controlled studies. DATA SYNTHESIS: ER metoprolol succinate is a controlled-release tablet designed to produce even and consistent beta(1)-blockade throughout the 24-hour dosing interval, with less fluctuation in metoprolol plasma concentrations compared with immediate-release metoprolol. Three randomized, double-blind, placebo-controlled trials have evaluated the efficacy of ER metoprolol succinate in the treatment of patients with chronic heart failure. The MERIT-HF (Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure) study, the largest of these trials and the largest randomized mortality trial with beta-blockers in heart failure to date, demonstrated that ER metoprolol succinate reduced the relative risk of all-cause mortality by 34% versus placebo. Furthermore, the relative risk of the combined endpoint of mortality plus all-cause hospitalizations was reduced by 19% and sudden death was reduced by 41%. The benefits of therapy were evident in various patient subgroups, including elderly patients and those with diabetes mellitus. ER metoprolol succinate was generally well tolerated, with a similar proportion of patients discontinuing therapy due to adverse events relative to placebo (9.8% and 11.7%, respectively). CONCLUSIONS: ER metoprolol succinate therapy provides substantial mortality and morbidity benefits in patients with New York Heart Association class II and III heart failure who are stabilized on angiotensin-converting enzyme inhibitors and diuretics. ER metoprolol succinate is administered once daily, is well tolerated, and provides consistent beta(1)-blockade over the 24-hour dosing interval.     

倍他乐克在慢性心力衰竭中的应用

目的观察比较倍他乐克在治疗慢性心衰病人中的疗效。方法146例慢性心衰患者随机分成两组,一组给予倍他乐克6.25 mg,口服,每天2次;另一组为空白对照,给予安慰剂,口服,每天2次,疗程均为1个月。结果两组采用不同药物治疗的患者群体短期死亡率方面χ^2=0.098,P〉0.05,两样本率间差异没有统计学意义;在1年内并发症出现率χ^2=3.982,P〈0.05,长期预后方面χ^2=4.419,P〈0.05,差异有统计学意义。结论小剂量倍他乐克选择性阻断β1受体,降低心肌的耗氧量,对抗儿茶酚胺的心脏毒性作用,在改善症状、防止并发症、改善患者长期预后等方面,倍他乐克要优于对照组。     

Management of hypertension in chronic heart failure

Chronic heart failure (CHF) is associated with frequent hospitalizations and high mortality. It affects more than 5 million individuals in the USA, and another 660,000 new cases are diagnosed each year; overall, heart failure (HF) now accounts for 7% of all deaths from cardiovascular disease. Hypertension (HTN) increases the risk of development of HF and it precedes it in 75% of cases. HF patients are nearly evenly divided between those with reduced left ventricular (LV) function or systolic dysfunction and those with preserved LV systolic function or diastolic dysfunction. The management of HTN in patients with CHF is challenging. Drugs such as β-blockers, angiotensin-converting enzyme inhibitiors, angiotensin receptor blockers, aldosterone receptor blockers, hydralazine and nitrates, which have shown mortality benefit in CHF and exert antihypertensive effects, should be used as first-line agents to control HTN in CHF. In addition, antihypertensive drugs such as α-receptor blockers that can increase mortality in HF should be avoided. The dihydropyridine group of calcium channel blockers are good antihypertensive medications with a neutral effect on mortality in patients with CHF. These may be used in CHF patients with refractory HTN. In patients with HF with reduced ejection fraction, HTN is treated differently in comparison to patients with HF with normal ejection fraction. This article reviews the treatment of essential HTN in patients at risk for developing HF, in the presence of HF and the latest developments in treatment that might benefit both HTN and HF management.     

Carvedilol: use in chronic heart failure

Carvedilol is a beta-adrenergic antagonist with vasodilatory properties (alpha1-antagonism), which has been extensively evaluated in the treatment of patients with heart failure. In patients with chronic heart failure carvedilol improves left-ventricular (LV) ejection fraction over 6 to 12 months of treatment, and attenuates LV remodelling. Large-scale randomised, placebo controlled trials involving more than 4000 patients with chronic heart failure have demonstrated that carvedilol improves survival and reduces hospitalizations. Comparative studies with metoprolol in patients with heart failure have suggested that carvedilol may be associated with greater survival benefit although differences in the preparation of metoprolol have left uncertainty in this area. Carvedilol has a high safety profile and the clinical benefits appear maintained across a wide range of patients with comorbidities such as diabetes and renal failure. Carvedilol has also been shown to attenuate LV remodeling and improve clinical outcomes in patients with LV dysfunction and/or heart failure following acute myocardial infarction. As a result of these data, carvedilol is recommended for treatment of patients with heart failure in heart-failure guidelines. This evidence-based treatment should be widely implemented to ensure that patients with heart failure receive appropriate medical therapy.     

Outpatient management of chronic heart failure

Critical to the success of managing heart failure is appropriate outpatient follow up. Various models of care integrate medical care, pharmacologic intervention, and patient education and support. Key factors in any program are frequent patient assessment with rapid response to even subtle changes in the patient's condition. As the disease progresses, alternative care options such as palliative care and hospice should be integrated into the patient's care regimen.     

The pathophysiology of chronic heart failure

Although the reduction in cardiac function is the cause and central abnormality of heart failure, there is clearly a very wide range of abnormalities in other systems that contribute to both the symptoms and progression of the syndrome of CHF. We must be aware of these changes to use the available therapeutic options to maximal effect, as well as being aware that more effective novel treatment strategies await a better understanding of the cause and effect of these noncardiac abnormalities that constitute the syndrome of CHF.     

Surgical treatment for chronic heart failure

Advances in the surgical treatment of chronic heart failure including ventricular re-modeling, artificial heart technology and bridge to recovery have revolutionized cardiac surgical management. This article summarizes the most popular surgical treatment of heart failure with experiences from various institutes. The author has stated that he does not have a significant financial interest or other relationship with any product manufacturer or provider of services discussed in this article.     

疾病名称

背景：病人，张先生，63岁，因“扩张型心肌病，心衰”在2年内住院5次。由于疾病反复发作，经常住院，张先生觉得生活没有了希望，经常唉声叹气，愁眉不展。床位护士来到张先生床边，开始了他们的谈话。