Digoxin Therapy in Chronic Heart Failure

Digitalis has been used for more than 250 years, but its role in the treatment of chronic heart failure has been intensively investigated only during the past two decades. Digoxin increases cardiac output both at rest and during exercise, alone or in combination with ACE inhibitors, and these hemodynamic effects are sustained during chronic therapy. A daily dose of digoxin that achieves a serum concentration of approximately 1.2 ng/ml is associated with a significant improvement in central hemodynamics, particularly in patients with impaired cardiac function despite pretreatment with diuretics and ACE inhibitors. Acute administration of digoxin in patients with chronic heart failure has an immediate sympathoinhibitory effect, and chronic therapy is associated with a sustained decrease in serum norepinephrine concentration. Discontinuation of digoxin in patients with chronic heart failure resulted in hemodynamic deterioration, which was reversed when the drug was readministered. Randomized withdrawal of digoxin in patients receiving only diuretics (PROVED study), or its withdrawal in patients receiving diuretics and ACE inhibitors (RADIANCE study), was associated with worsening of the clinical evidence of heart failure and a decrease in left ventricular systolic function in both studies. In the only large-scale, placebo-controlled mortality study reported thus for (DIG Trial), 7788 patients received standard drug treatment for chronic heart failure in addition to either digoxin or placebo. Digoxin had no impact on survival over the 37 months of follow-up, but the incidence of hospitalizations due to worsening heart failure was significantly reduced in patients receiving the drug compared with those receiving placebo.     

Role of the renin-angiotensin-aldosterone system in atrial fibrillation and cardiac remodeling

PURPOSE OF REVIEW: This review summarizes recent clinical trial evidence showing a reduction in the development and recurrence of atrial fibrillation with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor-blocking agents (ARBs). It then explores the possible mechanisms for this effect based on current animal models and limited human study. RECENT FINDINGS: Post hoc analyses of trials in patients with heart failure, hypertension, or myocardial infarction have observed reductions in atrial fibrillation among patients treated with ACE inhibitors or ARBs. Recent studies of these agents in animal models of atrial fibrillation suggest that they may prevent atrial fibrillation by reversing the cardiac structural and electrical changes, known as cardiac remodeling, that lead to the development of atrial fibrillation. This concept is also supported by two prospective studies showing that ACE inhibitors and ARBs prevent the recurrence of atrial fibrillation after electrical cardioversion. SUMMARY: Inhibition of the renin-angiotensin-aldosterone system is a novel concept for the treatment of atrial fibrillation that may target the underlying substrate of atrial fibrillation. Further human research is required to determine whether ACE inhibitors and ARBs prevent atrial fibrillation, and if so, whether this is a result of blood pressure lowering alone or a specific effect of these agents. Ongoing research will establish whether ACE inhibitors or ARBs have specific benefits in patients with atrial fibrillation.     

Role of Beta-Blocker Therapy in Heart Failure and Atrial Fibrillation

Heart failure is a serious disorder associated with substantial morbidity and mortality. Approximately 15-30% patients with systolic heart failure are in atrial fibrillation and the proportion increases with severity of heart failure. Patients with heart failure and atrial fibrillation have worse outcome than those in sinus rhythm. Beta-blockers, together with angiotensin-converting enzymes inhibitors, are the standard therapy in patients with chronic heart failure. Retrospective studies have suggested that despite the improvement in left ventricular systolic function after treatment with beta-blockers, the exercise capacity and symptoms in those heart failure patients with atrial fibrillation was not improved as much as those in sinus rhythm. Moreover, the use of bisoprolol in the Cardiac Insufficiency Bisoprolol Study II, unlike those in sinus rhythm, failed to produce any survival benefit in patients with poor systolic function and atrial fibrillation. It seems that those patients with heart failure and atrial fibrillation may have different response to beta-blocker therapy. Prospective trials to clarify the impact of beta-blocker therapy and the optimal therapeutic strategy in this high-risk group of patients are warranted.     

Digoxin for atrial fibrillation: a drug whose time has gone?

For over 200 years digitalis compounds have been used to treat atrial fibrillation. The rapid ventricular response to atrial fibrillation is frequently treated with digoxin to produce a controlled heart rate. Digoxin has also been proposed as a treatment for terminating recent-onset atrial fibrillation, for maintaining sinus rhythm after an episode of atrial fibrillation, and as prophylactic therapy in patients with paroxysmal atrial fibrillation to prevent excessive tachycardia during a paroxysm. Perhaps because it has been used for so long, few of these indications have been studied scientifically until recently. Studies now suggest that in patients with atrial fibrillation, digoxin is a poor drug for controlling heart rate during exertion, has little or no effect in terminating the arrhythmia, and may occasionally aggravate paroxysmal atrial fibrillation. Despite adequate digitalization, the heart rate at the onset of a paroxysm of fibrillation in patients receiving the drug does not differ from the heart rate in patients not receiving it. This article discusses the current role of digoxin in the management of patients with chronic, recent-onset, or paroxysmal atrial fibrillation.     

Angiotensin receptor blockers and cardiac rhythm disorders

Angiotension Receptor Blockers (ARB) are able to prevent the occurrence of atrial fibrillation (AF) through various mechanisms among them: neurhumoral antagonism and hemodynamic control. This occurs during arterial hypertension and chronic heart failure both diseases known to be associated with left atrial dysfunction. In the CHARM program, candesartan reduced by 20% the incidence of AF and thus also mortality and the incidence of hospitalisation for heart failure related to AF This beneficial effect is also observed with ACE inhibitors but is more important and potentated by ARB. In the Val-Heft study, valsartan on the top of standard treatment including ACE inhibitors, significantly lowered the cases of AF In hypertensive patients, ARB are more powerful than ACE inhibitors for the prevention of AF In the LIFE study, patients in the losartan arm had 33% less AF than patients from the other arm, despite treatment with atenolol and similar blood pressure reduction. Moreover ARB beside their specific effects are also able to increase efficiency of anti-arrhythmic agent; since after cardioversion patients treated with amiodarone plus irbesartan had a lower rate of recurrence of atrial fibrillation than patients treated with amiodarone alone. Finally ARB may reduce the risk of sudden death by ventricular arrhythmias in patients with diabetes mellitus.     

Drug Insight: angiotensin-converting-enzyme inhibitors and atrial fibrillation--indications and contraindications

Large clinical trials have demonstrated that angiotensin-converting-enzyme (ACE) inhibitors are associated with beneficial outcomes in patients with arterial hypertension, heart failure, coronary artery disease, or a combination of these conditions. Other reports have suggested that ACE inhibitors prevent the development or recurrence of atrial fibrillation (AF), a common arrhythmia. In the TRACE trial, in patients with reduced left ventricular function after myocardial infarction, trandolapril reduced the frequency of AF. In the SOLVD trial, a 78% reduction in the frequency of AF after infarction was noted with enalapril compared with placebo. Studies in patients with persistent AF undergoing cardioversion suggest that ACE inhibitors improve outcomes and prevent AF recurrences. The mechanism of AF prevention by ACE inhibitors is unclear, but experimental data show prevention or attenuation of pacing-induced atrial remodeling with ACE inhibitor use. ACE inhibitors decrease angiotensin II concentration; angiotension II stimulates mitogen-activated protein kinases, which in turn activate fibrosis formation and lead to conduction heterogeneity and induction of AF. On the other hand, AF induces atrial dilatation, atrial stretch and atrial secretion of ACE. Among other properties, ACE inhibitors have a sympatholytic effect and increase baroreceptor sensitivity. This review discusses the current data on the use of ACE inhibitors for AF prevention. Although these drugs represent a promising therapeutic option for AF patients, the data so far seem only supportive rather than definitive. Prospective trials are required to validate the benefit of ACE inhibitors and to investigate which patients are most likely to benefit from this pharmacological therapy.     

Digoxin prescribing for heart failure in elderly residents of long-term care facilities

BACKGROUND: Digoxin is often used in long-term care (LTC) residents with heart failure despite a high risk of toxicity associated with increased age, comorbidities and polypharmacy. This toxicity may occur at serum digoxin concentrations that are as low as 1.54 nmol/L. OBJECTIVES: To determine the prevalence of digoxin use, estimate the proportion at risk of toxicity and identify correlates of digoxin use in LTC residents with heart failure. METHODS: Cross-sectional survey in eight LTC facilities that lodge a total of 1223 residents. RESULTS: The prevalence of heart failure was 20%. Digoxin was prescribed for 32% of residents with heart failure and was associated with arrhythmia (primarily atrial fibrillation), anticoagulant and diuretic use, and higher serum thyroid-stimulating hormone. Digoxin doses higher than those that achieve the recommended therapeutic peak body stores of 6 microg/kg and 10 microg/kg were prescribed to 80% and 33% of residents with heart failure, respectively. Serum digoxin concentrations were greater than 1.5 nmol/L in 30% of patients. Comorbidities and concurrently prescribed medications that increase the risk of digoxin toxicity were prescribed to 26% of the patients. CONCLUSIONS: Approximately one-third of LTC residents with heart failure received digoxin. Atrial fibrillation was the most important determinant of use. At least 26% of these residents were exposed to an increased risk of digoxin toxicity. Studies are required to determine safe and effective digoxin dosing regimens for frail elderly heart failure patients. Clinicians should exercise caution when using digoxin in LTC residents.     

What is the optimal angiotensin-converting enzyme inhibitor dose in heart failure?

Doses of angiotensin-converting enzyme (ACE) inhibitors used in the landmark heart failure trials that demonstrated survival benefit are rarely reached in routine practice. The authors review the current literature regarding optimal dosing of ACE inhibitors in heart failure with specific focus on neurohormonal, functional capacity, and clinical outcomes. Neurohormonal studies have shown that lower ACE inhibitor dosing may provide inadequate suppression of the renin-angiotensin-aldosterone system. Higher doses of ACE inhibitors have resulted in greater increments in exercise and functional capacity. Clinically, patients on high-dose ACE inhibitor therapy had significant reductions in all-cause mortality or hospitalization, cardiovascular hospitalizations, and heart failure-specific hospitalizations. There is, however, conflicting evidence, and so continued uncertainty exists regarding optimal dosing. Despite underutilization of ACE inhibitors, there is insufficient evidence to support lower doses. Likewise, limited data exist for doses higher than those used in the landmark trials. Clinicians should therefore attempt to reach target doses in heart failure whenever possible.     

The management of heart failure - an overview

National and international societies have issued guidelines on the management of heart failure: The European Society of Cardiology, WHO, ACC / AHA Task Force Report, US Department of Health and Human Services, German Society of Cardiology. The therapeutic approaches to heart failure have undergone considerable changes during the last few years. The guidelines have to be updated almost yearly due to new results from prospective randomized studies. Although an agreement could be reached with respect to general measures and drug treatment, no agreement on mechanical devices, pacemakers and surgical interventions has been reached. The basic for medical treatment of chronic heart failure depends on diuretics, digitalis, ACE inhibitors, and beta-blockers. Calcium antagonists and other positive inotropic drugs, other than digitalis, should be avoided as far as possible. Thiazides, loop diuretics and aldosterone antagonists are needed for acute and chronic treatment of heart failure, alone or in combination (diuretic resistant heart failure!). Digitalis glycosides are needed in patients with atrial fibrillation with a fast ventricular rate or atrial flutter and in patients with systolic dysfunction, large hearts and symptomatic failure class NYHA III and IV. However, digitalis does not convert atrial fibrillation to sinus rhythm. Today there is no question that ACE inhibitors improve the prognosis of all patients with heart failure in all stages, if ejection fraction is reduced. Therefore, most patients after myocardial infarction or after having experienced pump failure due to myocarditis or cardiomyopathy are treated with ACE inhibitors and diuretics. The beneficial effects of ACE inhibitors seem to be most pronounced the worse the situation is. Relative risk reductions (mortality!) between 10% and 40% have been published depending on the severity of symptomatic left ventricular dysfunction. Those patients with high absolute risk have more to gain than those with low risk for any given "risk reduction", of course. Recent studies also indicate that most high risk cardiac patients profit from ACE inhibitors even if pump function is normal(i.e., patients with coronary heart disease, diabetes mellitus, cerebral vascular disease, hypertension)(15). AT₁ antagonists can substitute for ACE inhibitors, if the latter are not tolerated due to cough. Up to now, beta-blocking agents apart from diuretics seem to be the best investigated drugs in heart failure. Large controlled studies with bisoprolol, carvedilol and metoprolol in addition to diuretics, digitalis and ACE inhibitors convincingly yielded positive results in chronic left ventricular failure patients. Reduction of mortality by 35% and even of sudden cardiac deaths by 40% have been proven beyond doubt. Thus, heart failure patients today should also receive beta-blocking agents in all stages of the disease. In the era of controlled prospective studies (evidence-based medicine), physicians are well advised to use only drugs that have been proven beneficial in large controlled studies.     

Role and optimal dosing of angiotensin-converting enzyme inhibitors in heart failure

Based on overwhelming data demonstrating reduced morbidity and mortality, ACE inhibitors form a mainstay of therapy in all patients with symptomatic left ventricular systolic dysfunction. Furthermore, ACE inhibitors may be beneficial in the prevention of heart failure in patients with high-risk cardiovascular profiles. However, definite benefit from the use of ACE inhibitors in all patients with heart failure and preserved ejection fraction has not been demonstrated. Even though ACE inhibitors probably have a class effect in patients who have heart failure, it is recommended that ACE inhibitors that have been shown to reduce morbidity and mortality in clinical trials (captopril, enalapril, lisinopril, and ramipril) be used because studies have clearly defined a dose for these agents that is effective in modifying the natural history of the disease. Attempts should be made to up titrate patients to target doses of ACE inhibitors that have been used in clinical trials, if tolerated.     

Therapy of dilated cardiomyopathy with digitalis, diuretics and vasodilators

The treatment of dilated cardiomyopathy is primarily concerned with that of congestive heart failure. Digitalis is widely use in dilated cardiomyopathy but an improvement in the prognosis has not yet been demonstrated. Furthermore, the effects of digitalis in patients with sinus rhythm are debatable. If dilated cardiomyopathy induces atrial fibrillation and tachyarrhythmia, digitalis should be used. Diuretics are helpful in the treatment of congestive heart failure associated with dilated cardiomyopathy. By reducing hypervolemia and by venous dilatation, diuretics lower preload and afterload. This leads to relief of congestion and termination of the vicious cycle of congestive heart failure. Accordingly, the prognosis of dilated cardiomyopathy might be improved by diuretics. There are numerous diuretics acting differently on the renal tubules, the choice of which depends on the renal function and serum electrolyte concentrations. Reduction of preload and afterload improves congestive heart failure as has been demonstrated repeatedly. Many substances have therefore been used for arterial and venous dilation with differing results. At least for short-term periods, congestion is reduced and cardiac output increases. Especially inhibitors of angiotensin II converting enzyme are very effective since they act both in the arterial and venous systems. Additionally, inhibition of the action of angiotensin may be regarded as causal therapy since the renin-angiotensin system is the trigger for vasoconstriction and fluid retention in congestive heart failure. Unlike other substances, ACE inhibitors have been demonstrated to improve prognosis of patients with congestive heart failure. At present, combined diuretic therapy and angiotensin conversion enzyme inhibition would seem the most reasonable treatment for patients with dilated cardiomyopathy and sinus rhythm. If atrial fibrillation and tachyarrhythmia develop, additional digitalis therapy is effective.     

Management of heart failure in Canadian long-term care facilities

BACKGROUND: In long-term care (LTC) facilities, heart failure is common but undertreated. No Canadian studies of heart failure in LTC facilities have been reported. OBJECTIVES: To estimate the prevalence of heart failure in Canadian LTC facilities; to document the management of heart failure in LTC; and to describe characteristics of LTC residents with heart failure and predictors of adherence to treatment guidelines. METHODS: Cross-sectional survey in eight LTC facilities lodging 1223 residents. RESULTS: The prevalence of heart failure was 20%. LTC residents with heart failure were older, more often women, and more functionally impaired and burdened by comorbidity than were participants in heart failure trials. Documentation supporting the heart failure diagnosis was inadequate, with some symptoms possibly misattributed to chronic obstructive pulmonary disease. Angiotensin-converting enzyme (ACE) inhibitors were prescribed to 55% of residents, although only 45% received appropriate doses. Residents with hypertension or diabetes mellitus, using nitrates or who were male were more likely to receive ACE inhibitors. Appropriate ACE inhibitor doses were associated with functional impairment, nitrate use and recent hospitalization. Documentation of systolic dysfunction was associated with a greater likelihood of ACE inhibitor use. Beta-blockers were prescribed to 25% of residents, who were more likely to be using nitrates, have ischemic heart disease or had been recently hospitalized, and less likely to have chronic obstructive pulmonary disease. Residents with atrial fibrillation were more likely to be prescribed digoxin. Potentially hazardous regimens were prescribed to 43% of residents. CONCLUSIONS: Heart failure is common in Canadian LTC facilities. Management of heart failure in LTC does not conform to guidelines. Improved diagnostic methods tailored for frail elderly patients must be developed. Studies are needed to understand and identify factors influencing prescribing for heart failure medication in LTC.     

Euro heart failure survey. Medical treatment not in line with current guidelines

Summary It was the aim of the Euro Heart Survey on Heart Failure to assess whether patients are being treated according to current guidelines.Methods In Germany, patients were screened in 7 medical centers if their discharge diagnoses were myocardial infarction, a new episode of atrial fibrillation, or diabetes mellitus. Patients were enrolled if at least one additional criterion was fulfilled: (1) clinical diagnosis of heart failure, (2) hospital admission due to heart failure within the last 3 years, (3) therapy with loop diuretic, (4) medication for heart failure or ventricular dysfunction documented by echocardiography within the past 24 hours prior to death.Results 2166 patients were screened of whom 747 were included in the study (478 men, 269 women). 93% of the patients suffered from heart failure. Despite the high number of patients with known heart failure (ischemic heart failure in 71%), only 72% received ACE inhibitors and 62% β-blockers. Average daily dose met recommendations in only 63% of patients on ACE inhibitors and 54% on β-blockers. 74% of the patients received diuretics (furosemide 36%, thiazide 34%, spironolactone 17%).Conclusion An inadequately low number of patients with heart failure receives medical therapy according to guidelines, despite all the overwhelming evidence for improved morbidity and mortality. Awareness of physicians needs to be improved.     

Dosing of ACE inhibitors in postinfarct protection

Summary ACE inhibitors improve not only symptoms and signs of heart failure in patients with symptomatic left ventricular dysfunction but also lead to a slower progression of heart failure. In asymptomatic patients with left ventricular dysfunction, the progression to symptomatic heart failure is retarded by ACE inhibitors. As heart failure is preceded in about 80% by myocardial infarctions, trials were designed to influence the development of heart failure after myocardial infarction. It could be shown that therapy with ACE inhibitors ameliorates the progressive left ventricular dilatation and that this effect is translated into a significant increase of life expectancy. Mainly based on the CONSENSUS I study, large doses of ACE inhibitors were used in most subsequent trials. The mean daily doses of enalapril were 18.4 mg in the CONSENSUS I trial and 16.6 and 16.7 mg in both arms of the SOLVD trial. There is a trend towards lower doses of ACE inhibitors, as in the SAVE trial only 79% of the patients taking captopril received the target dose of 150 mg daily. Smaller studies used similar target doses, but a beneficial effect on left ventricular enlargement has been shown with a daily dose of only 75 mg captopril. Based on the hypothesis that the left ventricular enlargement is mainly determined by the activation of the local cardiac renin angiotensin system, even lower, and therefore better tolerated, doses of ACE inhibitors may prove effective. However, studies comparing the effect of different doses of ACE inhibitors on left ventricular remodeling are missing. Consequently, the above-mentioned target doses of ACE inhibitors should be aimed at when treating patients after myocardial infarction. Even when the doses have to be reduced because of side effects such as worsening angina or hypotension, there is good evidence that the progressive left ventricular dilatation will still be retarded.     

Digoxin—A redundant drug in congestive cardiac failure

Summary Controversy continues concerning the use of digoxin as a positive inotropic agent in the treatment of heart failure in patients in sinus rhythm. Digoxin is properly used to control the heart rate in patients in atrial fibrillation. The findings from 14 uncontrolled and 6 controlled clinical trials have been examined. Digoxin does exert a small chronic positive inotropic effect. Although some individual patients, particularly those with fluid overlond, appear to benefit from digoxin, controlled clinical trials in patients, most of whom have been treated with diuretics, have failed to demonstrate an Increase of exercise capacity. No mortality trial has been attempted. Digoxin has the potential to be harmful in patients with ischemic heart disease. Alternative and safer therapies have been shown to be equal or superior to digoxin.     

Value of Digoxin in Heart Failure and Sinus Rhythm: New Features of an Old Drug?

Digoxin has been a controversial drug since its introduction >200 years ago. Although its efficacy in patients with heart failure and atrial fibrillation is clear, its value in patients with heart failure and sinus rhythm has often been questioned. In the 1980s, reports of some large-scale trials indicated that digoxin, with or without vasodilators or angiotensin-converting enzyme inhibitors, reduced signs and symptoms of congestive heart failure and improved exercise tolerance. This beneficial influence was mainly found in patients with more advanced heart failure and dilated ventricles, whereas the effect in those with mild disease appeared to be less pronounced. In the last few years, new data have shown that digoxin may also have clinical value in mild heart failure, either when used in combination with other drugs or when administered alone. As neurohumoral activation has increasingly been recognized to be a contributing factor in the disease progression of chronic heart failure, the modulating effects of digoxin on neurohumoral and autonomic status have received more attention. Also, there is evidence that relatively low doses of digoxin may be at least as effective as higher doses and have a lower incidence of side effects. Further, the recognition that the use of digoxin too early after myocardial infarction may be harmful and the development of other drugs, in particular angiotensin-converting enzyme inhibitors, have obviously changed the place of digoxin in the treatment of chronic heart failure. The large-scale survival trial by the Digitalis Investigators Group (DIG), whose preliminary results have recently been presented, has shown that although digoxin has a neutral effect on total mortality during long-term treatment, it reduces the number of hospital admissions and deaths due to worsening heart failure. The potentially new features of the old drug digoxin are discussed in this review.     

Atrial fibrillation

The prevalence and incidence of atrial fibrillation increase with age. Atrial fibrillation is associated with a higher incidence of coronary events, stroke, and mortality than sinus rhythm. A fast ventricular rate associated with atrial fibrillation may cause tachycardia-related cardiomyopathy. Management of atrial fibrillation includes treatment of underlying causes and precipitating factors. Immediate direct-current cardioversion should be performed in persons with atrial fibrillation associated with acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta-blockers, verapamil, or diltiazem may be used to immediately slow a fast ventricular rate associated with atrial fibrillation. An oral beta-blocker, verapamil, or diltiazem should be given to persons with atrial fibrillation if a rapid ventricular rate occurs a rest or during exercise despite digoxin. Amiodarone may be used in selected persons with symptomatic life-threatening atrial fibrillation refractory to other drug therapy. Nondrug therapies should be performed in persons with symptomatic atrial fibrillation in whom a rapid ventricular rate cannot be slowed by drug therapy. Paroxysmal atrial fibrillation associated with the tachycardia-bradycardia syndrome should be managed with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in persons with atrial fibrillation in whom symptoms such as dizziness or syncope associated with non-drug-induced ventricular pauses longer than 3 seconds develop. Elective direct-current cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than medical cardioversion in converting atrial fibrillation to sinus rhythm. Unless transesophageal echocardiography shows no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective direct-current or drug cardioversion of atrial fibrillation and continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer the treatment strategy of ventricular rate control plus warfarin rather than to maintain sinus rhythm with antiarrhythmic drugs, especially in older patients. Digoxin should not be used in persons with paroxysmal atrial fibrillation. Patients with chronic or paroxysmal atrial fibrillation who are at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio (INR) of 2.0 to 3.0. Persons with atrial fibrillation who are at low risk for stroke or who have contraindications to warfarin should receive 325 mg aspirin daily.     

Atrial fibrillation in heart failure: catheter and surgical interventional therapies

Atrial fibrillation and heart failure commonly coexist in the same patient. Each may adversely affect the other. Atrial fibrillation leads to heart failure exacerbation, left ventricular function deterioration and an increase in thrombo-embolic risk. Therapeutic options targeting atrial fibrillation in heart failure patients include pharmacological and non-pharmacological means. Pharmacological therapy is directed at either rate control using nodal blocking agents or rhythm control using anti-arrhythmic agents, of which the options are limited in patients with heart failure. The landmark AF–CHF trial did not show any benefit of rhythm control strategy as opposed to rate control in patients with heart failure and atrial fibrillation. However, patients in this trial as well as in others used mostly amiodarone for rhythm control. This might have negated any positive effects of achieving normal sinus rhythm. Non-pharmacological therapy both for rate and rhythm control is appealing. This includes AV node ablation for rate control, catheter ablation of atrial fibrillation and surgical therapy of atrial fibrillation. This review will address non-pharmacologic treatment of AF in heart failure patients.     

Arrhythmias and their treatment in patients with heart failure

Heart failure is almost without exception associated with arrhythmias, which may be either supraventricular or ventricular. Supraventricular arrhythmias include frequent supraventricular extrasystoles, and episodic or chronic atrial fibrillation. The absence of atrial contraction may further reduce cardiac output, as may impaired control of QRS frequency. Therefore, supraventricular arrhythmias may be markers of the degree of heart failure and these arrhythmias will respond to heart failure therapy including diuretics, nitrates and, possibly, angiotensin-converting enzyme (ACE) Inhibitors. Ventricular rate will be controlled by cardiac glycosides and further rate reduction obtained by verapamil or diltiazem. The rationale for this therapy is to optimize heart rate without compromising contractility. Severe heart failure is generally accompanied by severe ventricular arrhythmias including repetitive forms.

Improving left ventricular function by ACE inhibition is accompanied by a reduction in the number of ventricular premature complexes and also a reduction in the rate of ventricular tachycardia. ACE inhibition reduces mortality but does not seem to influence sudden death rate, and sudden death patients may have different neurohormonal responses compared with patients destined to die of progressive heart failure. Uncontrolled trials with class IA or class III antiarrhythmic drugs have suggested that prognosis may be improved, but other studies have pointed out the increased risk of proarrhythmic responses in patients with low ejection fraction.     

Sudden Cardiac Death in Dilated Cardiomyopathy – Therapeutic Options

BACKGROUND: Despite routine use of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and spironolactone in patients with heart failure due to dilated cardiomyopathy (DCM), these patients still have a considerable annual mortality rate of 5-10%. Sudden unexpected death accounts for up to 50% of all deaths and is most often due to rapid ventricular tachycardia or ventricular fibrillation and less often due to bradyarrhythmias or asystole. THERAPEUTIC OPTIONS: The use of beta-blockers in patients with heart failure has been shown to improve overall mortality considerably. This survival benefit has been demonstrated for bisoprolol, metoprolol and carvedilol. Therefore, one of these three beta-blocking agents should be administered routinely starting with low doses in all patients with New York Heart Association (NYHA) class II or III heart failure in addition to ACE inhibitors, unless there is a contraindication to beta-blocker use. In addition, NYHA class IV heart failure patients have been shown to benefit from carvedilol therapy, if tolerated. The conflicting results of GESICA and CHF-STAT studies do not support a strategy of "prophylactic" amiodarone therapy in patients with DCM in order to prevent sudden cardiac death. Despite growing evidence that implantable cardioverter defibrillator (ICD) therapy results in improved overall survival py preventing sudden cardiac death in patients at high risk for serious arrhythmic events, arrhythmia risk stratification with regard to prophylactic ICD implantation remains highly controversial in patients with DCM. CONCLUSION: This review describes potential arrhythmia mechanisms in DCM and summarizes the results of antiarrhythmic drug trials and of prophylactic ICD trials in patients with heart failure as well as our knowledge concerning arrhythmia risk stratification in patients with DCM.