Multidisciplinary and multisetting team management programme in heart failure patients affects hospitalisation and costing.

BACKGROUND: We evaluated whether multidisciplinary disease management programme developed with collaboration of physicians and nurses inside and outside general district hospital settings can affect clinical outcomes in heart failure population over a 12-month period. METHODS: 571 patients hospitalised with CHF were referred to our unit and 509 patients agreed to participation. The intervention team included physicians and nurses from Internal Medicine and Cardiac Dept., and the patient's general practitioners. Contacts were on a pre-specified schedule, included a computerised programme of hospital visits and phone calls; in case of NYHA functional class III and IV patients, home visits were also planned. RESULTS: The median age of patients was 77.7+/-9 years (43.3% women). At baseline the percentage of patients with NYHA class III and IV was 56.0% vs. 26.0% after 12 months (P<0.05). Programme enrolment reduced total hospital admissions (82 vs. 190, -56%, P<0.05), number of patients hospitalised (62 vs. 146, 57%, P<0.05). All NYHA functional class benefited (class I=75%, class IV=67%), with reduction in the costing (-48%, P<0.05). Improvement in symptoms (-9.0+/-3.2) and signs (-5.2+/-3.1) scores was measured (P<0.01). Therapy optimisation was obtained by 20.5% increase in patients taking betablockade and 21.0% increase in those on anti-aldosterone drugs. CONCLUSIONS: Multidisciplinary approach to CHF management can improve clinical management, reducing hospitalisation rate and costing.

Biventricular pacing in patients with heart failure and intraventricular conduction delay.

In patients with advanced chronic heart failure, characterized by prolonged QRS duration and by decreased cardiac contractility, decreasing dysynchrony by biventricular pacing seems to improve exercise tolerance (6-min walk distance), symptoms (New York Health Association class), and quality of-life scores. Although the results of several reports were consistent, the numbers of patients studied were small, and many of the changes were trends that did not reach statistical significance. The availability of a non-pharmacological treatment that improves exercise capacity and quality-of-life would be a major advance. However, further studies will need to address the question of mortality and morbidity benefits of such intervention.

[Prognostic value of supraventricular arrhythmias in heart failure]. / Valore prognostico delle aritmie sopraventricolari nello scompenso cardiaco.

Supraventricular tachyarrhythmias can be responsible for severe hemodynamic derangement which may contribute to the progression and worsening of heart failure. The resultant effect of these arrhythmias, however, is conditioned by several concomitant factors, such as age of the patients, left ventricular systolic function, and ventricular rate response. If the role of such arrhythmias in functional class, morbidity, and functional capacity is well accepted, controversial data are available on their role on mortality in patients with heart failure.

Effects of diltiazem pretreatment on direct-current cardioversion in patients with persistent atrial fibrillation: a single-blind, randomized, controlled study.

BACKGROUND: Electric conversion of atrial fibrillation is the most widely used and effective treatment for sinus rhythm restoration. However, it has a limited success rate and a high recurrence rate. HYPOTHESIS: Pretreatment with calcium channel blocker may improve the efficacy by reversing the so-called "electric remodeling" phenomenon, also related to overload in cytosolic calcium. METHODS: The efficacy of diltiazem or amiodarone pretreatment (oral, 1 month before and 1 month after conversion) on direct-current conversion of persistent atrial fibrillation was assessed in 120 patients, randomly assigned to 3 matched groups: A (n = 44, diltiazem); B (n = 46, amiodarone), and C (n = 30, digoxin). RESULTS: Before electric conversion, all treatments significantly decreased mean heart rate. Spontaneous conversion to sinus rhythm was achieved in 6% of patients of group A (3 of 46) versus 25% of group B (11 of 44) and 3% (1 of 30) of group C (A/C vs B, P < .005). Current conversion was more successful in group B (91%) compared with group A (76%) and group C (67%) (B vs A/C, P < .05), with no difference in the electric threshold for effective conversion (P = not significant). At the 24-hour time point, early relapse of atrial fibrillation was similar between groups A and B (A, 2%; B, 3%; P = not significant) and lower than group C (12%) (P < .01), whereas at the 1-month time point the recurrence rate was lower in group B (28%) versus groups A (56%) and C (78%) (B vs A/C, P < .01). No significant side effects were reported. CONCLUSIONS: Although diltiazem seems to be as effective as amiodarone in reducing early atrial fibrillation recurrences, diltiazem is less effective in determining spontaneous or electric conversion, with a higher recurrence rate at 2 months. Diltiazem pretreatment could be considered as only a second choice treatment in those patients in whom amiodarone is contraindicated.

[Changes in the cardiac rhythm in ischemic cardiopathy]. / Le alterazioni del ritmo cardiaco nella cardiopatia ischemica.

Ventricular arrhythmia associated with ischemic heart disease has an important role in the etiology of sudden death, both in acute and chronic coronary syndromes. The etiopathogenesis of ventricular arrhythmia is strictly linked to the time-course from the occurrence of coronary occlusion. In the very acute phase of the ischemia, ventricular arrhythmias are due to a reentry mechanism, while 4-8 hours after occlusion the enhanced automatism, and triggered activity are the key mechanisms. Therefore reentry mechanisms are the main factors responsible for postinfarction arrhythmias. Also autonomic mechanisms, electrolytes and pharmacological therapy may contribute to cause arrhythmias.

Emerging concepts in exercise training in chronic heart failure.

There are objective similarities between heart failure and muscular deconditioning. Deficiencies in peripheral blood flow and skeletal muscle function, morphology, metabolism and function are present. The protective effects of physical activity have been elucidated in many recent studies: training improves ventilatory control, metabolism and autonomic nervous system. Exercise training seems to induce its beneficial effects on the skeletal muscle both directly (on function, histological and biochemical characteristics) and indirectly by reducing the activation of the muscle neural afferents (ergoreceptors). On this basis a skeletal muscle origin of symptoms in heart failure has been proposed. The possible metabolic mediators of ergoreceptors are currently being under investigation and they could be a possible target of therapy in heart failure symptoms.

Oral amiodarone increases the efficacy of direct-current cardioversion in restoration of sinus rhythm in patients with chronic atrial fibrillation.

AIMS: Direct current cardioversion of persistent atrial fibrillation is one of the most widely used and effective treatments for the restoration of sinus rhythm, but may be hampered by a low success rate and a high percentage of early recurrence. Pre-treatment with amiodarone or a glucose-insulin-potassium solution could improve the efficacy of electrical cardioversion by reversing the partially depolarized diastolic potential of the subsidiary pacemakers in atrial fibrillation. In a controlled randomized study, we assessed the effectiveness of electrical cardioversion in patients with persistent atrial fibrillation after pre-treatment with amiodarone or potassium infusion and the efficacy of amiodarone in maintaining sinus rhythm after electrical cardioversion. METHODS AND RESULTS: Ninety-two patients with persistent atrial fibrillation (>2 weeks duration) were prospectively randomized into three matched groups: A (n=31, oral amiodarone 400 mg. day(-1)1 month before and 200 mg. day(-1)2 months after cardioversion), B (n=31, 180 mg. day(-1)oral diltiazem 1 month before and 2 months after cardioversion and 80 mmol potassium, 50 UI insulin in 500 ml 30% glucose solution 24 h before cardioversion) and C (n=30, control patients, 180 mg. day(-1)oral diltiazem 1 month before and 2 months after cardioversion). Before cardioversion all patients were under 4 weeks effective oral anticoagulant therapy (warfarin). Before electrical cardioversion, the rate of spontaneous conversion to sinus rhythm was higher in group A (25%) than groups B (6%) or C (3%) (P<0.005). Electrical cardioversion was more successful in group A (88%) than groups B (56%) or C (65%) (P<0.05), while the electrical thresholds for effective cardioversion were lower in group B than the other groups (P<0.05). Twenty-four hours after cardioversion, the early recurrence of atrial fibrillation was similar in the three groups (P=ns), while at 2 months the recurrence rate was lower in group A (32%) than groups B (56%) or C (52%) (P<0.01). CONCLUSION: Pre-treatment with low-dose oral amiodarone, compared with oral diltiazem or glucose-insulin-potassium treatments, induces a significantly high percentage of instances of spontaneous conversion, increases electrical cardioversion efficacy and reduces atrial fibrillation recurrence.

The role of EP-guided therapy in ventricular arrhythmias: beta-blockers, sotalol, and ICD's.

Arrhythmic death can be reduced by antiarrhythmic drugs to a range of 24%. Electrophysiologic study by testing noninducibility of ventricular arrhythmia represents the classic method for evaluating the effectiveness of drug therapy. Several clinical studies have shown thaat sotalol suppresses VT induction and prevents arrhythmias recurrences at long term follow-up in 23% to 67% of patients. The efficacy of sotalol EP guided therapy in preventing VT/VF is not necessarily related to prevention of sudden death. In the ESVEM study the superiority of d,l-sotalol to other antiarrhythmic drugs was confirmed. The response to programmed ventricular stimulation was found to be strongly predictive for arrhythmia free state while the failure of sotalol therapy to suppress VT at the EP study was associated with an high recurrence rate (40%). However, EP study failes to predict freedom from sudden death. The beta-blocking activity of racemic sotalol may account for some of the observed survival benefit.Beta-blockers therapy reduces mortality in patients after myocardial infarction primarily by a reduction of sudden death. A reduction of death, worsening heart failure and life threatening ventricular arrhythmias was shown in a recent study on carvedilol. In the prospective study of Steinbeck the EP guided-therapy did not improve the overall outcome when compared to metoprolol. Suppression of inducible arrhythmias by antiarrhythmic drugs was associated with a better outcome. The effectiveness of defibrillator therapy in reducing overall mortality, has been uncertain since great clinical trials have been concluded. MADIT, AVID and CASH trials confirmed the superiority of ICD therapy over antiarrhythmic drugs therapy: ICD should be considered the first choice therapy in post-cardiac arrest patients. The ongoing BEST Trial will give us further responses about the interaction between EP study and metoprolol effect compared to ICD in patients post myocardial infarction also focusing on tolerability and compliance of the beta-blocking therapy in patients with low ejection fraction. In this study will be useful to optimize therapy in patients at high risk of sudden death.

Clinical potential of emerging antiarrhythmic agents.

Analyses of randomised clinical trials have suggested that only in selective populations may antiarrhythmic drugs be effective in improving prognosis: therapy of cardiac arrhythmias, in contrast to other cardiovascular pathological conditions, has not been fully successful. The ideal treatment of arrhythmias should be guided by a sound understanding of the relative arrhythmogenic mechanisms and vulnerable parameters of the different arrhythmias. New model agents are pure class III agents, developed to fulfil these ideal characteristics and are now under active investigation (dofetilide, ibutilide, azimilide, ambasilide, E 4031, almokalant, sematilide, RP 58866 and tedisamil).

Comparison of therapy detection times between implantable cardioverter defibrillators with standard dual- and single-chamber pacing.

Previous implantable cardioverter defibrillators (ICDs) required patients in need of dual-chamber (DDD) pacing for improved hemodynamic status to undergo implantation of separate devices to treat bradycardia and/or ventricular arrhythmias. An investigation was conducted to verify the performance of a new ICD that combines both therapies.Sixty-nine patients at 17 European and Canadian centers were implanted with VENTAK AV models 1810/1815, ICD's that includes DDD pacing and algorithms designed to differentiate between atrial and ventricular arrhythmias. 36 of the cohort were compared to 32 patients tested at six centers with an external test device (VENTAK MINI). In both cohorts detection times were calculated for ventricular fibrillation (VF) induced at implant. The mean detection times (DT) from the VENTAK AV device were compared to the DT from the VENTAK MINI device. Patient characteristics of the VENTAK AV and the VENTAK MINI control groups were similar. Mean VF detection time (+/-SD) with the VENTAK AV device was 2.21 +/- 0.54 seconds, as compared with 1.87 +/- 0.62 seconds with the VENTAK MINI (p < 0.01), indicating that the difference in means did not exceed one second. The VENTAK AV system function did not demonstrate interaction with the pacemaker function, as indicated by the clinical significance with the detection times of the study device. The difference in detection times between cohorts did not statistically exceed one second. Appropriate detection of the new ICD was not compromised by the addition of the dual-chamber pacing therapy.

Capture window in human atrial fibrillation: evidence of an excitable gap.

INTRODUCTION: Local capture of atrial fibrillation (AF) was shown in animal experiments for a wide range of pacing rates, thus demonstrating the existence of an excitable gap. The aim of this study was to assess the existence of an excitable gap in human AF by studying the mechanism of local control and acceleration of AF over a wide range of pacing rates and by evaluating the time window of capture. METHODS AND RESULTS: Recording and stimulation of electrical activity in the right atrium during AF was performed by a monophasic action potential (MAP) contact electrode catheter in 17 patients with lone AF during electrophysiologic study. Stimulation was started at pacing intervals close to the mean AF interval, and the time window of capture was estimated by lengthening or shortening the pacing interval until capture was lost. Pacing intervals shorter than the minimum cycle length for capture were also tested. Beat-to-beat measurements of AF intervals during pacing were performed. Atrial MAP signal showed rapid irregular activity with an average AF interval of 151.3 +/- 16.1 msec and SD of 21.3 +/- 5.2 msec. Rapid pacing with a cycle length slightly shorter or longer than the mean AF interval resulted in local capture of AF. The width of time window of capture ranged from 22 to 36 msec, with a mean value of 28.8 +/- 4.9 msec. The average minimum pacing interval of stable capture was 129.2 +/- 19.5 msec, while the maximum was 158.1 +/- 18.7 msec, corresponding to 85% and 104% of mean AF cycle length, respectively. Pacing too rapidly resulted in a transient acceleration of AF, with an average shortening of fibrillation interval from 149.8 +/- 16.6 to 123.2 +/- 15.1 msec (P < 0.01). CONCLUSION: Local capture is feasible during AF in humans over a wide range of pacing rates, indicating the possibility of regional control of the fibrillatory process. This result demonstrates the presence of an excitable gap during AF in human atria.

Safety of oral propafenone in the conversion of recent onset atrial fibrillation to sinus rhythm: a prospective parallel placebo-controlled multicentre study.

AIM: Oral propafenone is effective in restoring sinus rhythm however the proarrhythmic effects are still unknown. The Safety Antiarrhythmic Therapy Evaluation (SATE) trial was a prospective randomized placebo-controlled multicentre study which evaluated the safety of acute oral loading dose of propafenone in patients with recent onset atrial fibrillation. Secondary end-points were to evaluate the effect of digitalis added to propafenone in ventricular rate control and the efficacy of propafenone alone or added to digitalis compared with efficacy of digitalis plus quinidine. METHODS AND RESULTS: 246 patients (126 male; 58+/-11 years) with atrial fibrillation of <48 h duration were randomly allocated to one of four groups: digitalis 0.75-1 mg i.v. plus quinidine 1100 mg (D+Q, 70 patients); propafenone 450-600 mg orally (PNF, 66 patients); propafenone 450-600 mg orally plus digitalis 0.750-1 mg i.v. (PNF+D, 70 patients); placebo (Pl, 40 patients). All patients underwent 24-h ECG Holter monitoring. Safety was assessed by evaluating the appearance of adverse events classified as mild, moderate and severe. No severe adverse events were reported. Short lasting asymptomatic atrial flutter episodes with atrio-ventricular conduction > or =2:1 were observed in 14% of the D+Q group, 21% PNF, 18% PNF+D and in 8% Pl. One patient in the D+Q group and four in the PNF+D group showed asymptomatic runs of 3-4 ventricular ectopic beats. Reversible sinus atrial blocks (<3 s) were detected in two patients of the D+Q group and in two of the PNF group. In patients with persistent atrial fibrillation the ventricular rate was similar in the four study groups. At 3 h the high efficacy of propafenone was confirmed. At the 24th hour no differences were found between active treatment and placebo arms. CONCLUSION: Propafenone in a single oral loading dose is safe and promptly effective in patients with recent onset atrial fibrillation.

The role of oral 1C antiarrhythmic drugs in terminating atrial fibrillation.

Antiarrhythmic drug therapy still remains the mainstay in the management of many supraventricular and ventricular arrhythmias. Several studies have recently pointed out the role of orally administered class 1C drugs in terminating atrial fibrillation. These drugs can play an important role in the ambulatory management of selected patients. The electrophysiologic mechanisms of these antiarrhythmic drugs together with their pharmacologic properties and clinical indications are discussed according to the current literature.

Overview and meta-analysis of randomised trials of amiodarone in chronic heart failure.

Unlike other antiarrhythmic class I drugs, amiodarone showed in preliminary studies, benefits also in patients with left ventricular dysfunction. These positive results have induced the development of large randomised controlled studies: their results are reviewed and the controversial points are discussed. In a meta-analysis of randomised controlled trials the use of amiodarone in heart failure was associated with an approximate 20 to 25% reduction in deaths. However, amiodarone was also associated with a 120 to 124% increase in side effects.

Effects of Class III drugs on atrial fibrillation.

The Class III antiarrhythmic drugs have been used for the treatment of atrial fibrillation (AF); however, each has specific electrophysiologic properties that delineate different safety and/or effectiveness profiles. First-generation Class III agents seem to be more effective in preventing recurrence of AF than in converting AF to sinus rhythm. The high incidence of major cardiac and noncardiac side effects in the long term often requires discontinuation of the chronic antiarrhythmic therapy. The second-generation Class III drugs, ibutilide and dofetilide, have demonstrated interesting clinical applications, especially in the setting of atrial flutter. However, their favorable antiarrhythmic effect is counterbalanced by the high incidence of severe proarrhythmias. New promising experimental data suggest that the new Ikr-ks blockers may be free from these dangerous limitations, thus extending the indication of Class III drugs in the treatment of AF.

Clinical pharmacology of antiarrhythmic drugs.

Antiarrhythmic drugs play a major role in the management of the most common types of arrhythmias. The margin between the beneficial and toxic effects of these drugs is often narrow. Thus, a precise knowledge of dosages, drug-target tissue interactions, pharmacodynamics and pharmacokinetics of antiarrhythmic drugs is needed to better predict how effective a particular drug will be in the treatment of a specific arrhythmia in a given patient. Despite the large amount of information that is available on the electrophysiological and pharmacological effects of antiarrhythmic drugs, we still do not know enough about their true mechanism of action in individual patients. The results of the Cardiac Arrhythmia Suppression Trial (CAST) firmly established that the use of class I drugs is potentially dangerous in a specific subset of patients. Additionally, several meta-analyses have reported that quinidine has severe proarrhythmic effects in patients with atrial fibrillation. The management of arrhythmias in elderly patients is difficult because of age-related factors that may influence the pharmacokinetics and pharmacodynamics of antiarrhythmic drugs.

Risk of complications of atrial fibrillation.

Atrial fibrillation is associated with three major risk of complications: thromboembolism, hemodynamic compromise, and arrhythmogenesis. In patients with chronic atrial fibrillation the incidence of embolization is about 5% per year. The risk of embolism and in particular of stroke can be reduced by warfarin anticoagulation. Aspirin is generally less effective than warfarin, although it is probably more effective than placebo. The hemodynamic complications which may occur during atrial fibrillation are mainly due to the loss of effective atrial contraction, the irregular ventricular rhythm, and the possible excessively rapid ventricular rate. Sudden death is a recognized manifestation of Wolff-Parkinson-White syndrome and is considered to be precipitated by atrial fibrillation in the majority of patients. Torsades de pointes is perhaps the most widely recognized proarrhythmia associated with treatment of atrial fibrillation, especially with 1A antiarrhythmic drugs and sotalol. The chronic treatment with type 1C drugs in 3.5%-5% of patients may induce atrial flutter with 1:1 conduction with significant hemodynamic compromise.