Hugo Grancelli

Nonsustained ventricular tachycardia in severe heart failure : Independent marker of increased mortality due to sudden death

BACKGROUND The goal of the study was to determine the prognostic value of nonsustained ventricular tachycardia (NSVT) in total mortality in severe congestive heart failure (CHF) and in death modes. NSVT is associated with an increased mortality in CHF. However, the predictive value of NSVT as a marker for sudden death or death due to progressive heart failure has not been determined. METHODS AND RESULTS Five hundred sixteen patients from the GESICA trial (33.4% with NSVT) were initially studied with the results of 24-hour Holter and 2 years of follow-up. Within 2 years, 87 of 173 patients (50.3%) with NSVT and 106 of 343 patients (30.9%) without NSVT died. Relative risk (RR) was 1.69 (95% confidence interval [CI], 1.27 to 2.24; P < .0002), and Cox proportional hazard analysis was 1.62 (95% CI, 1.22 to 2.16; P < .001). Sudden death increased from 8.7% (30 of 343) to 23.7% (41 of 173) in patients with NSVT (RR, 2.77; 95% CI, 1.78 to 4.44; P < .001). Progressive heart failure death was also increased from 17.5% (60 of 343) to 20.8% (36 of 173) (P = .22). Quantitative analysis of 24-hour Holter (first 295 patients) demonstrated that couplets had a similar RR to that of NSVT for both total mortality (RR, 1.81; 95% CI, 1.22 to 2.66; P < .002) and sudden death (RR, 3.37; 95% CI, 1.57 to 7.25; P < .0005). Couplets and/or NSVT (ventricular repetitive beats) were even more predictive for sudden death (RR, 10.1; 95% CI, 1.91 to 52.7; P < .01). CONCLUSIONS In patients with CHF, NSVT is an independent marker for increased overall mortality rate and sudden death. The absence of NSVT and ventricular repetitive beats in a 24-hour Holter indicates a low probability of sudden death.

I Latin American Guidelines for the assessment and management of decompensated heart failure

Edimar Alcides Bocchi, Fabio Vilas-Boas, Sergio Perrone, Angel G Caamano, Nadine Clausell, Maria da Consolacao VMoreira, Jorge Thierer, Hugo Omar Grancelli, Carlos Vicente Serrano Junior, Denilson Albuquerque, Dirceu Almeida,Fernando Bacal, Luis Felipe Moreira, Adonay Mendonza, Antonio Magana, Arturo Tejeda, Daniel Chafes, Efraim Gomez,Erick Bogantes, Estela Azeka, Evandro Tinoco Mesquita, Francisco Jose Farias B Reis, Hector Mora, Humberto Vilacorta,Jesus Sanches, Joao David de Souza Neto, Jose Luis Vuksovic, Juan Paes Moreno, Julio Aspe y Rosas, Lidia ZytynskiMoura, Luis Antonio de Almeida Campos, Luis Eduardo Rohde, Marcos Parioma Javier, Martin Garrido Garduno, MucioTavares, Pablo Castro Galvez, Raul Spinoza, Reynaldo Castro de Miranda, Ricardo Mourilhe Rocha, Roberto Paganini,Rodolfo Castano Guerra, Salvador Rassi, Sofia Lagudis, Solange Bordignon, Solon Navarette, Waldo Fernandes, AntonioCarlos Pereira Barretto, Victor Issa, Jorge Ilha Guimaraes.

Heart Rate Is a Marker of Amiodarone Mortality Reduction in Severe Heart Failure

OBJECTIVES The impact of amiodarone on mortality in patients with severe congestive heart failure (CHF) (New York Heart Association functional classes II [advanced], III and IV; left ventricular ejection fraction < 35%) In the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) trial was analyzed in relation to initial mean baseline heart rate (BHR) and its change after 6 months of follow-up. BACKGROUND Trials of amiodarone therapy in CHF have produced discordant results, suggesting that the effect is not uniform in all patient subgroups with regard to survival. METHODS The present analysis was carried out in 516 patients randomized to receive amiodarone, 300 mg/day (n = 260), or nonantiarrhythmic therapy (n = 256, control group) and followed up for 2 years. Survival was evaluated for patients with a BHR > or = 90 beats/min (control: n = 132; amiodarone: n = 122) and < 90 beats/min (control: n = 124; amiodarone: n = 138). Survival was also analyzed according to heart rate reduction at 6 months for 367 patients. RESULTS For patients with a BHR > or = 90 beats/min, amiodarone therapy reduced mortality to 38.4% compared with 62.4% in control patients (relative risk [RR] 0.55, 95% confidence interval [CI] 0.35 to 0.95, p < 0.002). Both sudden death (RR 0.46, 95% CI 0.24 to 0.90, p < 0.02) and progressive heart failure death (RR 0.60, 95% CI 0.30 to 1.03, p < 0.06) were reduced, and functional capacity was improved. In patients with a BHR < 90 beats/min, amiodarone did not alter survival. Among 367 patients who completed 6 months of follow-up, amiodarone reduced 2-year mortality only in those with a BHR > or = 90 beats/min, which was reduced at 6 months. CONCLUSIONS Elevated rest heart rates in severe CHF identify a subgroup of patients who benefit from treatment with amiodarone. Amiodarone-induced heart rate slowing may be an important benefit for patients.

Omega-3 Fatty Acids for the Prevention of Recurrent Symptomatic Atrial Fibrillation: Results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) Trial

OBJECTIVES The aim of this study was to evaluate the efficacy of polyunsaturated fatty acids (n-3 PUFA) for the prevention of recurrent atrial fibrillation (AF) in patients with normal sinus rhythm. BACKGROUND Current pharmacological treatments to limit recurrent AF in patients with previous AF have limited efficacy and high rates of adverse events. Results of trials that tested the efficacy of n-3 PUFA provided heterogeneous results. METHODS This was a prospective, randomized, double-blind, placebo-controlled, multicenter trial involving 586 outpatient participants with confirmed symptomatic paroxysmal AF that required cardioversion (n = 428), at least 2 episodes of AF in the 6 months before randomization (n = 55), or both (103). Patients were randomly allocated to n-3 PUFA (1 g/day) or placebo for 12 months. The primary endpoint was symptomatic recurrence of AF. RESULTS There were no significant differences between patients allocated to placebo and those who received n-3 PUFA for the main outcome. At 12 months, 56 of 297 participants (18.9%) in the placebo group and 69 of 289 participants (24.0%) in the n-3 PUFA group had a recurrent symptomatic AF (hazard ratio: 1.28, 95% confidence interval: 0.90 to 1.83, p = 0.17). There was no difference between treatment with placebo and n-3 PUFA for any of the other pre-specified endpoints, including the composite of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding that occurred in 20 (6.7%) and 16 (5.5%) of patients randomized to placebo or n-3 PUFA, respectively (hazard ratio: 0.86, 95% confidence interval: 0.44 to 1.66, p = 0.65). CONCLUSIONS Pharmacological supplementation with 1 g of n-3 PUFA for 1 year did not reduce recurrent AF. (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation [FORWARD]; NCT00597220).

N-3 Polyunsaturated Fatty Acids to Prevent Atrial Fibrillation: Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background Previous studies have suggested that n‐3 polyunsaturated fatty acids (n‐3 PUFAs) have antiarrhythmic effects on atrial fibrillation (AF). We aimed to assess the effects of therapy with n‐3 PUFAs on the incidence of recurrent AF and on postoperative AF. Methods and Results Electronic searches were conducted in Web of Science, Medline, Biological Abstracts, Journal Citation Reports, and the Cochrane Central Register of Controlled Trials databases. In addition, data from the recently completed FORωARD and OPERA trials were included. We included randomized controlled trials comparing treatment with n‐3 PUFAs versus control to (1) prevent recurrent AF in patients who underwent reversion of AF or (2) prevent incident postoperative AF after cardiac surgery. Of identified studies, 12.9% (16 of 124) were included, providing data on 4677 patients. Eight studies (1990 patients) evaluated n‐3 PUFA effects on AF recurrence among patients with reverted AF and 8 trials (2687 patients) on postoperative AF. Pooled risk ratios through random‐effects models showed no significant effects on AF recurrence (RR, 0.95; 95% CI, 0.79 to 1.13; I2, 72%) or on postoperative AF (0.86; 95% CI, 0.71 to 1.04; I2, 53.1%). A funnel plot suggested publication bias among postoperative trials but not among persistent AF trials. Meta‐regression analysis did not find any relationship between doses and effects (P=0.887 and 0.833 for recurrent and postoperative AF, respectively). Conclusions Published clinical trials do not support n‐3 PUFAs as agents aimed at preventing either postoperative or recurrent AF. Clinical Trial Registration URL: http://www.crd.york.ac.uk/PROSPERO. Unique Identifier: CRD42012002199.

Clinical ResearchHeart Rhythm Disorders in Heart FailureOmega-3 Fatty Acids for the Prevention of Recurrent Symptomatic Atrial Fibrillation: Results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) Trial

OBJECTIVES The aim of this study was to evaluate the efficacy of polyunsaturated fatty acids (n-3 PUFA) for the prevention of recurrent atrial fibrillation (AF) in patients with normal sinus rhythm. BACKGROUND Current pharmacological treatments to limit recurrent AF in patients with previous AF have limited efficacy and high rates of adverse events. Results of trials that tested the efficacy of n-3 PUFA provided heterogeneous results. METHODS This was a prospective, randomized, double-blind, placebo-controlled, multicenter trial involving 586 outpatient participants with confirmed symptomatic paroxysmal AF that required cardioversion (n = 428), at least 2 episodes of AF in the 6 months before randomization (n = 55), or both (103). Patients were randomly allocated to n-3 PUFA (1 g/day) or placebo for 12 months. The primary endpoint was symptomatic recurrence of AF. RESULTS There were no significant differences between patients allocated to placebo and those who received n-3 PUFA for the main outcome. At 12 months, 56 of 297 participants (18.9%) in the placebo group and 69 of 289 participants (24.0%) in the n-3 PUFA group had a recurrent symptomatic AF (hazard ratio: 1.28, 95% confidence interval: 0.90 to 1.83, p = 0.17). There was no difference between treatment with placebo and n-3 PUFA for any of the other pre-specified endpoints, including the composite of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding that occurred in 20 (6.7%) and 16 (5.5%) of patients randomized to placebo or n-3 PUFA, respectively (hazard ratio: 0.86, 95% confidence interval: 0.44 to 1.66, p = 0.65). CONCLUSIONS Pharmacological supplementation with 1 g of n-3 PUFA for 1 year did not reduce recurrent AF. (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation [FORWARD]; NCT00597220).

The rationale and design of the FORωARD Trial: A randomized, double-blind, placebo-controlled, independent study to test the efficacy of n-3 PUFA for the maintenance of normal sinus rhythm in patients with previous atrial fibrillation

BACKGROUND Atrial fibrillation (AF) is associated with increased risk of death, thromboembolic complications, and a lowered quality of life. Despite this burden, pharmacologic agents for prevention of AF in patients who achieved normal sinus rhythm are of limited utility, mostly because of serious and frequent side effects. Thus, the availability of safer and more effective drugs may reduce the burden of disease. TRIAL DESIGN Patients aged > or =21 years with previous symptomatic AF and who have recovered normal sinus rhythm will be randomized to 1 g daily of omega-3-acid ethyl esters or identical placebo. To be included in the trial, patients must have either (a) at least 2 symptomatic episodes of documented AF in the 6 months before randomization, with the last episode occurring in the 14 to 90 days before randomization (paroxysmal AF), or (b) successful electrical or pharmacologic cardioversion for persistent AF. Ethical committees of 71 cardiology centers in 16 provinces of Argentina have qualified and approved the protocol and are expected to enroll 1,400 patients to test the primary end point of efficacy, which is survival free of AF during follow-up. CONCLUSION The Fish Oil Reserach with omega-3 for Atrial fibrillation Recurrence Delay (FORomegaARD) trial will determine whether pharmacologic supplementation with 1 g of omega-3-acid ethyl esters can reduce AF recurrence in patients with previous AF who have recovered normal sinus rhythm.

Understanding the risk of hyperkalaemia in heart failure: role of aldosterone antagonism

The risk of hyperkalaemia in patients with heart failure has increased in the past few years together with the evolution of pharmacological treatment for these patients. This significant change has been associated with the introduction of angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and aldosterone antagonists. High potassium concentrations in heart failure could lead to life threatening events, and therefore should be taken seriously. In this review we summarise the information about potassium homeostasis in heart failure and the current risk of developing potentially serious hyperkalaemia, particularly in association with the use of aldosterone antagonists.

Impaired anti-platelet effect of aspirin, inflammation and platelet turnover in cardiac surgery

A reduced platelet inhibitory response to acetyl salicylic acid (ASA) has been associated with an increased risk of graft thrombotic occlusion after coronary artery bypass grafting (CABG). We performed a prospective, observational study of 18 patients on 100 mg/day ASA before and after CABG. We assessed antiplatelet response to ASA and its relationship with platelet turnover, inflammatory markers, and soluble thrombomodulin (sTM) levels. All patients showed optimal response to ASA preoperatively but had higher values during follow-up. Platelet aggregation and platelet count in the perioperative period were significantly associated (P=0.05). Platelet turnover was defined as the average daily turnover (ADTO). The lowest inhibitory value (28% of patients > or =6 Omega) was recorded at the same time of the highest platelet turnover (>10% daily in 77.77% of patients), one week after CABG. ADTO >10% was associated with an increased risk of platelet aggregation > or =6 Omega. Levels of sTM were significantly higher one week after CABG (median 13 vs. 3 ng/ml preoperatively, P=0.0011). There is a transient impairment in ASA antiplatelet effect after CABG related to an increased platelet turnover caused by the inflammatory process. This could be responsible for the high risk of occlusive thrombosis.

Telephone interventions for disease management in heart failure

Such support for patients at home cuts admissions to hospital for heart failure