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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atrial fibrillation (Afib) is clinically the most common arrhythmia. Its main complications are recurrent embolic events and a variable deterioration of functional class. Atrial fibrillation induces changes in cellular ionic channels that self-perpetuate the arrhythmia. The pharmacologic treatment of Afib is directed toward correction of those changes and return to sinus rhythm. It is also intended to maintain adequate heart rates and prevent embolic events through anticoagulation or platelet antiagregation. There are presently several class IC or class III antiarrhythmics available for attempting a return to sinus rhythm. The success rates are irregular, the best achieved with flecainide or propafenone among patients without structural heart disease. Amiodarone is the best choice when there is such a problem. The combination possibilities are huge, so that each case must be individualized. The new class III antiarrhythmics are very effective, but have a relatively high rate of side effects including torsade de pointes. Anticoagulation should be the preferred treatment among the majority of patients, but each case should be individually evaluated. New therapies such as focal or linear catheter ablation techniques, atrial or biatrial programmed stimulation, and atrial cardioverter-defibrillator need longer follow-up and experience to be objectively evaluated, although there are reasons to be optimistic in the future, even if patients need antiarrhythmic support at present. Surgery has high morbi-mortality rates, so it is not the preferred approach.
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PMID:[Atrial fibrillation. New views on an old disease]. 1169 12

The Fontan procedure has allowed to improve the outcome of complex congenital cardiopathy involving single ventricle. A better understanding of the systemic venous circulation has favored bicavo-bipulmonary derivation instead of atrio-pulmonary derivation. However, in spite of the improvement in surgical procedures, post-operative arrhythmias still occur with an increasing rate during follow-up reaching 40 to 50% of the patients in some series. We report a series of 52 patients of which 92% presented a severe atrial arrhythmia (atrial fibrillation or atrial flutter) during a 6-year follow-up. The outcome was worse in case of classic or modified Fontan (n=15) or direct dicavo-bipulmonary procedures (n=7). The non-modified Fontan group was characterized by a lower functional class (63% NYHA class I or II), more refractory atrial arryhthmias (37%), more deaths or transplanted patients (26%). Amiodarone was very effective in this context as opposed to the failure of class 1 anti-arrhythmic drugs. However, low dosage amiodarone in combination with a beta-blocker is recommended taking into account the important rate of amiodarone-induced side effects (53%). Atrial arrhythmia ablation was unsuccessful (8/10 failures). Anti-arrhythmic surgery (N=3) has been incompletely evaluated. In summary, transformation of failing Fontan procedures into bicavo-bipulmonary derivations seems to offer the best outcome at the price of a high surgical risk.
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PMID:[Late atrial tachycardia after Fontan-type procedure. Cooperative study of 52 cases]. 1208 43

Amiodarone is a drug that is widely used in the treatment of heart disease. To circumvent side effects, colloidal drug carriers have been designed to deliver the drug specifically to the site of action. For the purposes of in vitro characterization of such particles, difficult test systems are employed that usually require the quantitative separation of the drug carrier from the release medium before analysis. In this work, a Langmuir balance was used to characterize amiodarone release. Drug-loaded nanoparticles were prepared from a biodegradable polyester and assayed for their drug release kinetics. Simultaneously, nanoparticles were analyzed for their drug release by a standard procedure based on dialysis tubes combined with high-performance, liquid chromatography. The results obtained by the Langmuir balance experiments were compared with those obtained from high-performance liquid chromatography and were found to correlate well. The interexperimental variation was 4.4% for the Langmuir method (n = 4), and the interexperimental variation for HPLC was 2.9% (n = 3). The major advantage of this new method is the possibility diminishing significantly the required sample amount for the experiment, allowing drug detection in the lower nanomolar range. Moreover, the avoidance of prior nanoparticle separation from the release medium provides important progress of this technique. The Langmuir balance has proven its adaptability as a new sensitive tool for the characterization of amphiphilic drug release kinetics.
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PMID:A quantitative method for the determination of amphiphilic drug release kinetics from nanoparticles using a Langmuir balance. 1213 48

With beta-blockers as the exception, increasing doubt is emerging on the value of antiarrhythmic drug therapy following a series of trials that have either shown no mortality benefit or even an excess mortality. Vaughan Williams class I drugs are generally avoided in patients with structural heart disease, and class IV drugs are avoided in heart failure. Unfortunately, arrhythmias are a growing problem due to an increase in the incidence of atrial fibrillation and sudden death. The population is becoming older and more patients survive for a longer time period with congestive heart failure, which again increases the frequency of both supraventricular as well as ventricular arrhythmias. Class III antiarrhythmic drugs act by blocking repolarising currents and thereby prolong the effective refractory period of the myocardium. This is believed to facilitate termination of re-entry tachyarrhythmias. This class of drugs is developed for treatment of both supraventricular and ventricular arrhythmias. Amiodarone, sotalol, dofetilide, and ibutilide are examples of class III drugs that are currently available. Amiodarone and sotalol have other antiarrhythmic properties in addition to pure class III action, which differentiates them from the others. However, all have potential serious adverse events. Proarrhythmia, especially torsade de pointes, is a common problem making the benefit-risk ratio of these drugs a key question. Class III drugs have been evaluated in different settings: primary and secondary prevention of ventricular arrhythmias and in treatment of atrial fibrillation or flutter. Based on existing evidence there is no routine indication for antiarrhythmic drug therapy other than beta-blockers in patients at high risk of sudden death. Subgroup analyses of trials with amiodarone and dofetilide suggest that patients with atrial fibrillation may have a mortality reduction with these drugs. However, this needs to be tested in a prospective trial. Similarly, subgroups that will benefit from prophylactic treatment with class III antiarrhythmic drugs may be found based on QT-intervals or - in the future - from genetic testing. Class III drugs are effective in converting atrial fibrillation to sinus rhythm and for the maintenance of sinus rhythm after conversion. This is currently by far the most important indication for this class of drugs. As defined by recent guidelines, amiodarone and dofetilide have their place as second-line therapy except for patients with heart failure where they are first line therapy being the only drugs where the safety has been documented for this group of high risk patients.
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PMID:A benefit-risk assessment of class III antiarrhythmic agents. 1224 Nov 26

In managing atrial fibrillation (AF), the main therapeutic strategies include rate control, termination of the arrhythmia, and the prevention of recurrences and thromboembolic events. Safety and efficacy considerations are important in optimizing the choice of an antiarrhythmic drug for the treatment of AF. Recently approved antiarrhythmics, such as dofetilide, and promising investigational drugs, such as azimilide and dronedarone, may change the treatment landscape for AF. For medical conversion of recent-onset AF, class IC antiarrhythmic drugs, administered as an oral bolus, have been demonstrated to be the most efficacious pharmacologic conversion agents. Intravenous ibutilide and oral dofetilide both have efficacies superior to placebo in controlled trials for converting persistent AF. Comparative trials in paroxysmal AF have demonstrated that flecainide, propafenone, quinidine, and sotalol are equally effective in preventing recurrences of AF. Amiodarone has been demonstrated to be more efficacious than propafenone or sotalol in the Canadian Trial of Atrial Fibrillation. In persistent AF, twice-daily dofetilide has been shown to be as or more effective than low-dose sotalol given twice daily for the maintenance of sinus rhythm in patients with AF. Trials have demonstrated that subjective adverse effects are less frequent with class IC drugs, sotalol, and dofetilide compared with such drugs as quinidine. In patients without structural heart disease, flecainide, propafenone, and D,L-sotalol are the initial drugs of choice, given their reasonable efficacy, low incidence of subjective side effects, and lack of significant end-organ toxicity. Treating AF in patients with left ventricular dysfunction can be difficult because of associated electrophysiologic derangements, potential proarrhythmic concerns, and negative inotropic effects of antiarrhythmics. Some data exist suggesting that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can prevent AF either by preventing atrial dilation and stretch-induced arrhythmias or by blocking the renin-angiotensin system. In post-myocardial infarction patients, D,L-sotalol, dofetilide, and amiodarone-and in congestive heart failure patients, amiodarone and dofetilide-have demonstrated neutral effects on survival in controlled trials. In the Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STAT), amiodarone lowered the frequency of AF development and improved left ventricular ejection fraction over time. In CHF-STAT, there was lower mortality in patients who converted from AF to sinus rhythm. Dofetilide decreased rehospitalization for congestive heart failure in the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) trials. Neutral effects on survival and favorable hemodynamics have positioned amiodarone and dofetilide as the antiarrhythmics of choice in patients with left ventricular dysfunction. In post-myocardial infarction patients, sotalol is an additional agent to consider for treatment of AF in this setting.
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PMID:Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials. 1267 Jun 38

Pregnancy can precipitate cardiac arrhythmias not previously present in seemingly well individuals. Risk of arrhythmias is relatively higher during labor and delivery. Potential factors that can promote arrhythmias in pregnancy and during labor and delivery include the direct cardiac electrophysiological effects of hormones, changes in autonomic tone, hemodynamic perturbations, hypokalemia of pregnancy, and underlying heart disease. Paroxysmal supraventricular and ventricular tachycardia may cause hemodynamic compromise with consequences to the fetus. Management of arrhythmias in pregnant women is similar to that in non-pregnant but a special consideration must be given to avoid adverse fetal effects. No drug therapy is usually needed for the management of supraventricular or ventricular premature beats, but potential stimulants, such as smoking, caffeine, and alcohol should be eliminated. In paroxysmal supraventricular tachycardia, vagal stimulation maneuvers should be tried first. Adenosine or a cardioselective beta-blocker could be used if vagal maneuvers are ineffective. Alternatively, verapamil or diltiazem may be given. In pregnant women with atrial fibrillation, the goal of treatment is conversion to sinus rhythm or to control ventricular rate by a cardioselective beta-adrenergic blocker drug or digoxin. Ventricular arrhythmias may occur in the pregnant women with cardiomyopathy, congenital heart disease, valvular heart disease, or mitral valve prolapse. Termination of ventricular arrhythmias can usually be achieved by intravenous lidocaine or procainamide or by electrical cardioversion. Amiodarone is not safe for the fetus. Beta-blocker therapy must be continued during pregnancy and postpartum period in women with long QT syndrome and torsade de pointes.
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PMID:Cardiac arrhythmias in pregnancy: clinical and therapeutic considerations. 1271 90

Heart failure (HF) is a complex clinical syndrome resulting from any structural or functional cardiac disorder impairing the ability of the ventricles to fill with or eject blood. The approach to pharmacologic treatment has become a combined preventive and symptomatic management strategy. Ideally, treatment should be initiated in patients at risk, preventing disease progression. In patients who have progressed to symptomatic left ventricular dysfunction, certain therapies have been demonstrated to improve survival, decrease hospitalizations, and reduce symptoms. The mainstay therapies are angiotensin-converting enzyme (ACE) inhibitors and beta-blockers (bisoprolol, carvedilol, and metoprolol XL/CR), with diuretics to control fluid balance. In patients who cannot tolerate ACE inhibitors because of angioedema or severe cough, valsartan can be substituted. Valsartan should not be added in patients already taking an ACE inhibitor and a beta-blocker. Spironolactone is recommended in patients who have New York Heart Association (NYHA) class III to IV symptoms despite maximal therapies with ACE inhibitors, beta-blockers, diuretics, and digoxin. Low-dose digoxin, yielding a serum concentration <1 ng/mL can be added to improve symptoms and, possibly, mortality. The combination of hydralazine and isosorbide dinitrate might be useful in patients (especially in African Americans) who cannot tolerate ACE inhibitors or valsartan because of hypotension or renal dysfunction. Calcium antagonists, with the exception of amlodipine, oral or intravenous inotropes, and vasodilators, should be avoided in HF with reduced systolic function. Amiodarone should be used only if patients have a history of sudden death, or a history of ventricular fibrillation or sustained ventricular tachycardia, and should be used in conjunction with an implantable defibrillator [corrected]. Finally, anticoagulation is recommended only in patients who have concomitant atrial fibrillation or a previous history of cerebral or systemic emboli.
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PMID:Pharmacologic therapy for patients with chronic heart failure and reduced systolic function: review of trials and practical considerations. 1272 48

A 41 year old woman with type 2 diabetes, hypertension, and hyperlipidaemia but no known heart disease received 130 DC shocks for repeated cardiac arrests due to ventricular tachyarrhythmias over 48 hours. She was stabilised by intravenous amiodarone and had a defibrillator implanted. Serial ECGs did not change, but raised troponin I confirmed myocardial infarction as the underlying cause. Electrical storm is an uncommon and dramatic but usually treatable syndrome of recurrent ventricular arrhythmias. Frequent precipitants of electrical storm include recent worsening heart failure, hypokalaemia, hypomagnesaemia and myocardial ischaemia. Amiodarone is the antiarrhythmic agent of choice and implantable cardioverter defibrillator improves long term outcome.
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PMID:Successful resuscitation of a patient with electrical storm. 1274 67

The efficacy and safety of amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation was examined by reviewing the trials on the subject identified through a comprehensive literature search. Amiodarone has been used both intravenously (i.v.) and orally for the pharmacological cardioversion of recent-onset atrial fibrillation. Intravenous amiodarone has been used as a bolus only or as a bolus followed by a continuous i.v. infusion until conversion or up to 24 h. The dose of i.v. bolus given ranged from 3 to 7 mg/kg body weight and that of infusion from 900 to 3000 mg/day. The efficacy reported is 34-69% with the bolus only regimens, and 55-95% with the bolus followed by infusion regimens. Only the higher dose (>1500 mg/day) amiodarone is superior to placebo in converting recent-onset atrial fibrillation to sinus rhythm. The highest 24-h conversion rates have been reported with the i.v. regimen of 125 mg/h until conversion or a maximum of 3 g and the oral regimen of 25-30 mg/kg body weight administered as a single loading-dose (>90% and >85%, respectively). Most of the conversions occur after 6-8 h of the initiation of therapy. Predictors of successful conversion are shorter duration of atrial fibrillation, smaller left atrial size, and higher amiodarone dose. Amiodarone is not superior to the other antiarrhythmic drugs conventionally used for the pharmacological cardioversion of recent-onset atrial fibrillation but is relatively safe in patients with structural heart disease and in those with depressed left ventricle function. Therefore, amiodarone could be used particularly in patients with structural heart disease and in those with left ventricular systolic dysfunction as the use of class IC drugs, propafenone and flecainide, for cardioversion of atrial fibrillation is contraindicated in such patients.
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PMID:Amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation. 1276 48

ATP-sensitive K(+) (KATP) channels are present on the sarcolemma (sarcKATP channels) and mitochondria (mitoKATP channels) of cardiac myocytes. Amiodarone, a class III antiarrhythmic drug, reduces sudden cardiac death in patients with organic heart disease. The objective of the present study was to investigate the effects of amiodarone on sarcKATP and mitoKATP channels. Single sarcKATP channel current and flavoprotein fluorescence were measured in guinea pig ventricular myocytes to assay sarcKATP and mitoKATP channel activity, respectively. Amiodarone inhibited the sarcKATP channel currents in a concentration-dependent manner without affecting its unitary amplitude. The IC50 values were 0.35 microM in the inside-out patch exposed to an ATP-free solution and 2.8 microM in the cell-attached patch under metabolic inhibition, respectively. Amiodarone (10 microM) alone did not oxidize the flavoprotein. In addition, the oxidative effect of the mitoKATP channel opener diazoxide (100 microM) was unaffected by amiodarone. Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca(2+) overload, and the intensity of rhod-2 fluorescence increased to 246 +/- 16% of baseline (n = 9). Amiodarone did not alter the ouabain-induced mitochondrial Ca(2+) overload (236 +/- 10% of baseline, n = 7). Treatment with diazoxide significantly reduced the ouabain-induced mitochondrial Ca(2+) overload (158 +/- 15% of baseline, n = 8, p < 0.05 versus ouabain); this effect was not abolished by amiodarone (154 +/- 10% of baseline, n = 8, p < 0.05 versus ouabain). These results suggest that amiodarone inhibits sarcKATP but not mitoKATP channels in cardiac myocytes. Such an action of amiodarone may effectively prevent ischemic arrhythmias without causing ischemic damage.
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PMID:Amiodarone inhibits sarcolemmal but not mitochondrial KATP channels in Guinea pig ventricular cells. 1453 61


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