Abstract/Text: BACKGROUND: Frequent idiopathic premature ventricular complexes (PVCs) can result in a reversible form of left ventricular dysfunction. The factors resulting in impaired left ventricular function are unclear. Whether a critical burden of PVCs can result in cardiomyopathy has not been determined.
OBJECTIVE: The objective of this study was to determine a cutoff PVC burden that can result in PVC-induced cardiomyopathy.
METHODS: In a consecutive group of 174 patients referred for ablation of frequent idiopathic PVCs, the PVC burden was determined by 24-hour Holter monitoring, and transthoracic echocardiograms were used to assess left ventricular function. Receiver-operator characteristic curves were constructed based on the PVC burden and on the presence or absence of reversible left ventricular dysfunction to determine a cutoff PVC burden that is associated with left ventricular dysfunction.
RESULTS: A reduced left ventricular ejection fraction (mean 0.37 +/- 0.10) was present in 57 of 174 patients (33%). Patients with a decreased ejection fraction had a mean PVC burden of 33% +/- 13% as compared with those with normal left ventricular function 13% +/- 12% (P <.0001). A PVC burden of >24% best separated the patient population with impaired as compared with preserved left ventricular function (sensitivity 79%, specificity 78%, area under curve 0.89) The lowest PVC burden resulting in a reversible cardiomyopathy was 10%. In multivariate analysis, PVC burden (hazard ratio 1.12, 95% confidence interval 1.08 to 1.16; P <.01) was independently associated with PVC-induced cardiomyopathy.
CONCLUSION: A PVC burden of >24% was independently associated with PVC-induced cardiomyopathy.

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Abstract/Text: BACKGROUND AND METHODS: In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomization to encainide or flecainide or their respective placebo.
RESULTS: Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty.
CONCLUSIONS: There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown.

Abstract/Text: BACKGROUND: Metoprolol can improve haemodynamics in chronic heart failure, but survival benefit has not been proven. We investigated whether metoprolol controlled release/extended release (CR/XL) once daily, in addition to standard therapy, would lower mortality in patients with decreased ejection fraction and symptoms of heart failure.
METHODS: We enrolled 3991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy, in a double-blind randomised controlled study. Randomisation was preceded by a 2-week single-blind placebo run-in period. 1990 patients were randomly assigned metoprolol CR/XL 12.5 mg (NYHA III-IV) or 25.0 mg once daily (NYHA II) and 2001 were assigned placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analysed by intention to treat.
FINDINGS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the metoprolol CR/XL group than in the placebo group (145 [7.2%, per patient-year of follow-up]) vs 217 deaths [11.0%], relative risk 0.66 [95% CI 0.53-0.81]; p=0.00009 or adjusted for interim analyses p=0.0062). There were fewer sudden deaths in the metoprolol CR/XL group than in the placebo group (79 vs 132, 0.59 [0.45-0.78]; p=0.0002) and deaths from worsening heart failure (30 vs 58, 0.51 [0.33-0.79]; p=0.0023).
INTERPRETATION: Metoprolol CR/XL once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.

Abstract/Text: BACKGROUND: There have been 13 randomised controlled trials of prophylactic amiodarone in patients with recent myocardial infarction (MI) or congestive heart failure (CHF). None of these was powered to detect a mortality reduction of about 20%. We undertook a meta-analysis, based on data from individual patients, to provide a more sensitive and accurate assessment of the benefits and risks of prophylactic amiodarone.
METHODS: Individual data from the studies were abstracted according to a predefined protocol. The summary odds ratios were calculated according to standard methods.
FINDINGS: There were eight post-MI and five CHF trials; nine trials were double-blind and placebo-controlled, and four compared amiodarone with usual care. 6553 patients were randomly assigned treatment, of which 78% were in post-MI trials and 22% in CHF trials. 89% had had previous MI. The mean left-ventricular ejection fraction was 31%, and median frequency of ventricular premature depolarisation 18 per h. Total mortality was reduced by 13% (odds ratio 0.87 [95% CI 0.78-0.99], p = 0.030) based on classic fixed-effects meta-analysis and by 15% (0.85 [0.71-1.02], p = 0.081) with the more conservative random-effects approach. Arrhythmic/sudden death was reduced by 29% (0.71 [0.59-0.85], p = 0.0003). There was no effect on non-arrhythmic deaths (1.02 [0.87-1.19], p = 0.84). There was no difference in treatment effect between post-MI and CHF studies. The risk of arrhythmic/sudden death in control-group patients was higher in CHF than in post-MI studies (10.7 vs 4.1%), and the best single predictor of risk of arrhythmic/sudden death among all patients was symptomatic CHF. The excess (amiodarone minus control) risk of pulmonary toxicity was 1% per year.
INTERPRETATION: Prophylactic amiodarone reduces the rate of arrhythmic/sudden death in high-risk patients with recent MI or CHF and this effect results in an overall reduction of 13% in total mortality.

Abstract/Text: BACKGROUND: The prevalence, gender- and age-related differences, ablation success rate and inter-relationship between the origins of the idiopathic ventricular arrhythmias (I-VA) have not been clarified.
METHODS AND RESULTS: A total of 625 consecutive patients with symptomatic, drug resistant I-VA (315 males and 310 females; mean age, 54 ± 17 years; 218 ventricular tachycardias, 407 premature ventricular contractions) who underwent catheter ablation were studied. The patients were divided into 5 groups based on the VA origin: (1) outflow tract (OT)-VA, consisting of right ventricular (RV) OT-VA and left ventricular (LV) OT-VA; (2) inflow tract (IT)-VA, consisting of tricuspid annulus (TA)-free wall (FW)-VA, IT-septum-VA, and mitral (MA)-FW-VA; (3) LV-inferoseptum-VA; (4) LV-other-VA; and (5) RV-other-VA. RVOT-VA in women were 1.5 times more frequent than in men, while LVOT-VA were more frequent in men. The prevalence of LVOT origin I-VA increased with age compared to that for the RVOT. The mean age of MA-FW-VA patients (62 ± 14 years) was higher than that of TA-FW-VA patients (51 ± 18 years; P = 0.03). The ablation success rate for RVOT-VA (88%) was higher than that for LVOT-VA (58%; P<0.0001). A multivariate analysis revealed that the patient age was one of the valuable predictors of a successful ablation (odds ratio=0.97; 95% confidence interval: 0.95-0.99; P=0.007).
CONCLUSIONS: Distinct gender and age differences were found in the incidence of I-VA according to their site of origin.