Surgical treatment of congestive heart failure

Cardiac transplantation is the definitive surgical treatment for patients with severe left ventricular dysfunction and congestive heart failure. Unfortunately, however, the supply of donor hearts remains severely limited, so transplantation is an option for only a minority of these patients. Even after being approved for a heart transplant, patients often have a long wait until a suitable donor heart can be found. This waiting period entails a significant mortality rate. Because the supply of donor hearts is not expected to increase, surgeons have introduced several alternatives to heart transplantation, including partial left ventriculectomy, mitral valve repair, myocardial revascularization, and endoventricular circular patch plasty. For maximal benefit, surgeons must refine the selection criteria for determining which patients are the best candidates for each of these procedures.     

Pharmacologic treatment of congestive heart failure

Congestive heart failure is a clinical syndrome producing symptomatic deterioration, functional impairment, and shortened life span. The syndrome is complex in that it includes both peripheral and cardiac effects which contribute to the progression of heart failure. In the periphery, elevations in thesympathetic nervous system and renin-angiotensin system increase afterload and contribute to further salt and water retention. The central cardiac abnormalities include remodeling of the heart and downregulation of beta receptors. Traditional heart failure therapy has included treatment of fluid retention with diuretics, although their effect on mortality has never been addressed. The most proven therapy in heart failure is treatment with vasodilators, particularly angiotensin-converting enzyme (ACE) inhibitors. Improved survival with ACE-inhibitor therapy has been demonstrated in patients with severe heart failure (CONSENSUS), mild to moderate heart failure (SOLVD), and in comparison with vasodilator therapy with hydralazine isosorbide dinitrate (VHeFT II). Improved survival has also been noted in postmyocardial infarction when the ejection fraction is decreased (SAVE). The ACE inhibitors have now become standard therapy for heart failure regardless of severity. Additive vasodilator therapy with calcium-channel antagonists is under investigation. Inotropic therapy is controversial at present because of disappointing mortality results. The clinical mainstay digitalis remains without convincing mortality reduction data. Other inotropic agents, particularly phosphodiesterase inhibitors, have shown uniformly negative survival results. However, the new mixed action agents vesnarinone and pimobenden have shown favorable data, with vesnarinone demonstrating a mortality reduction effect. Beta-blocker therapy in heart failure has also found renewed interest, particularly with the new agents carvedolol and bucindolol which also have vasodilating properties.     

Pharmacotherapy in congestive heart failure: Hyperkalemia in congestive heart failure

Hyperkalemia is not an uncommon occurrence in the congestive heart failure patient, particularly when renal failure coexists. Hyperkalemia in CHF is typically medication-related. Its occurrence is inevitably linked to the simultaneous ingestion of angiotensin-converting enzyme inhibitors and beta-blockers, and more recently, aldosterone receptor antagonists, such as spironolactone. The most devastating consequence of hyperkalemia is its cardiotoxicity that can be fairly insidious in its rate of development. The therapy of hyperkalemia in congestive heart failure can involve both acute and semiacute management phases. Acute hyperkalemia management includes measures that block the adverse membrane effects of hyperkalemia, such as intravenous calcium administration, and efforts to shift potassium intracellularly, such as occurs with intravenous bicarbonate and/or inhaled beta-agonists. Semiacute management of hyperkalemia includes measures to increase urinary potassium excretion and administration of binding resins, such as Kayexalate?. Prevention is the cornerstone of hyperkalemia management in the heart failure patient and requires that careful attention be directed to both identifying exogenous sources of potassium and pinpointing the maximum tolerable dose of either an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker. (c)2001 by CHF, Inc.     

Nitrates in the treatment of congestive heart failure

Nitrates have been widely used for the treatment of patients with chronic congestive heart failure. Although the use of these drugs has not been evaluated by large-scale studies traditionally used for evaluation of new therapy, multiple studies over the years have demonstrated their favorable effects. Organic nitrates have been shown to have a beneficial effect on ischemia, hemodynamic profile, magnitude of mitral regurgitation, endothelial function, and cardiac remodeling. These drugs alone or in combination with hydralazine have improved exercise capacity, maximal oxygen consumption, cardiac function, and survival. The use of nitrates in patients with heart failure has been limited by reduced responsiveness (resistance) and early development of tolerance. Nitrate resistance is due to reduced vascular response and results in the need to use a larger dose of any nitrate preparation when used for the treatment of patients with heart failure compared to patients without heart failure. Recent information suggests that nitrate tolerance is caused by increased levels of superoxide at the vascular wall, which leads to reduced nitric oxide level and to increased sensitivity to vasoconstrictive mechanisms, such as endothelin and angiotensin II. Intermittent dosing of nitrates allowing a 12-hour nitrate-free interval is effective in preventing nitrate tolerance and is, therefore, recommended. Recent information suggests that augmentation of nitrate dose by the use of an escalating dose regimen and a concomitant use of hydralazine can prevent or overcome the effect of nitrate tolerance in patients with heart failure.     

The effect of treatment on survival in congestive heart failure.

Congestive heart failure (CHF) is a disorder characterized by a variety of clinical, biochemical, electrophysiological, and hemodynamic abnormalities. During the past two decades, numerous drugs have been employed in the treatment of this complex syndrome, and many agents have been shown to improve symptoms and ventricular function in patients with CHF. Because CHF is associated with a high risk of death, treatment should be directed not only toward the relief of symptoms, but also toward a reduction in mortality. Many variables have been shown to be related to survival; taken individually, however, each is limited in its utility in predicting prognosis. In recent years, large-scale studies with large sample sizes have directly assessed the effects of treatment on mortality in CHF. Results from these trials indicate that vasodilators and angiotensin-converting enzyme (ACE) inhibitors may improve mortality in patients with symptoms of heart failure. Additional trials are now in progress to evaluate the effect of treatment on patients with asymptomatic left ventricular dysfunction.     

Ventricular arrhythmia in congestive heart failure.

The importance of ventricular arrhythmia is based on its association with sudden death. In certain groups of patients, ventricular arrhythmia--primarily runs of nonsustained ventricular tachycardia (NSVT)--is associated with an increased risk for sudden death. Although this relationship has been most often reported in patients with recent myocardial infarction, it has also been recognized in patients with dilated cardiomyopathy, regardless of etiology. Therefore, ventricular arrhythmia is common in patients with CHF due to cardiomyopathy. A number of studies have reported that 70-95% of patients with cardiomyopathy and congestive heart failure (CHF) have frequent ventricular premature beats, and 40-80% will manifest runs of NSVT. Many factors are responsible for ventricular arrhythmia in such patients, including structural abnormalities, electrolyte imbalance, hemodynamic impairment, activation of neurohormonal mechanisms, and pharmacologic therapy. Many studies have reported a high yearly mortality in patients with cardiomyopathy and CHF; greater than 40% of deaths are sudden, most often the result of sustained ventricular tachyarrhythmia. Most studies have noted an association between presence (and frequency) of NSVT and risk of sudden cardiac death in these patients. Unfortunately, other techniques--such as the signal-averaged electrocardiogram and electrophysiologic testing--are not helpful in identifying the individual at risk. Although several drug interventions will reduce mortality from progressive CHF, these drugs have not been shown to reduce sudden death and, indeed, have a variable effect on ventricular arrhythmia. Although NSVT is a marker for increased risk for sudden death, it is uncertain if antiarrhythmic drugs will prevent this outcome. Antiarrhythmic drugs have not been shown to be effective for preventing sudden death, although there are as yet no well-controlled randomized trials. Several studies suggest that amiodarone and beta blockers are beneficial, but this requires confirmation. For patients who have been resuscitated following an episode of sudden death due to a sustained ventricular tachyarrhythmia, antiarrhythmic therapy guided by invasive and noninvasive techniques appears to reduce risk of recurrent arrhythmia. However, the response rate to antiarrhythmic agents is low and side effects are common in patients with CHF. Especially important is the increased risk of precipitating CHF and aggravating the arrhythmia being treated. For many such patients who have had serious ventricular tachyarrhythmia, the automatic implantable cardioverter defibrillator may prove a better option. Other drugs used for management of CHF reduce overall mortality, but not risk of sudden death.     

Plasma norepinephrine in congestive heart failure.

Resting plasma concentrations of norepinephrine, dopamine-beta-hydroxylase enzyme activity and peripheral blood lymphocyte beta adrenergic receptor sensitivity to isoproterenol as reflected in cyclic 3′,5′-adenosine monophosphate (cAMP) generation were studied in patients with congestive heart failure due to atherosclerotic heart disease or to congestive cardiomyopathy or hypertensive cardiovascular disease. Systolic time Intervals were also measured in nonhypertensive patients and correlated with the plasma norepinephrine concentration. Control patients were hospital employees without a previous history of heart disease or hypertension, and were matched for age to eliminate the effect of increasing age on the plasma norepinephrine concentration.The results of this study clearly demonstrate that the plasma norepinephrine concentration is directly related to the degree of left ventricular dysfunction in patients with congestive heart failure. When the systolic time intervals were correlated with the plasma norepinephrine levels, a significant prolongation of the preejection period was observed with progressively increasing plasma concentrations of norepinephrine. The reverse was true for the left ventricular ejection time, which demonstrated a significant Inverse relation with the plasma norepinephrine concentration. The ratio of the preejection period to the left ventricular ejection time, which is a reflection of left ventricular function, significantly increased with increasing levels of plasma norepinephrine. In addition, plasma lymphocytes from patients with the greatest degree of left ventricular dysfunction failed to generate normal amounts of cAMP after beta adrenergic receptor stimulation with isoproterenol. It Is suggested that beta adrenergic receptors are desensitized in these patients and that this desensitization contributes to the observed alterations in myocardial contractility.     

Digoxin and congestive heart failure.

The purpose of our study was to evaluate the absorption of digoxin in alcoholic solution in normal subjects and in patients on congestive heart failure whose water and electrolyte balances were determined. While the parameters of the distribution kinetics were not significantly different between the two groups, the areas under the serum concentration curve resulted increased in the patients on congestive heart failure indicating a more efficient absorption respect to the normal subjects.     

Doxazosin and congestive heart failure.

Congestive heart failure (CHF) is the most devastating cardiac sequella of long-standing hypertension. Recent data from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) have shown the risk of CHF to be twice as high with doxazosin than with chlorthalidone. Although some questions remain regarding the diagnosis and mortality of CHF in the doxazosin arm and regarding the risk of dying from malignancy in the diuretic arm of ALLHAT, drugs used to treat hypertension should lower the CHF risk. Therefore, until ironclad safety data are provided, doxazosin, and probably all alpha-blockers, should no longer be used as first-line antihypertensive therapy.     

替米沙坦治疗充血性心力衰竭的临床观察

目的 :观察替米沙坦治疗慢性充血性心力衰竭 （CHF）的临床疗效。方法 :经强心、利尿、扩血管等治疗 ,疗效不佳的 CHF患者 96例口服替米沙坦 4 0～ 80 mg,每天 1次 ,疗程 4周。观察治疗前后血压、心率、左室舒张末内径、左室射血分数以及心功能变化。结果 :4周治疗后血压、心率、左室舒张末内径均明显下降 （P<0 .0 5 ）。左室射血分数、心排出量、心脏排血指数等各项指标均明显增加 （P<0 .0 1） ,心功能改善 ,临床总有效率达 98% ,患者耐受性好。结论 ::替米沙坦治疗 CHF疗效好。