The atrial fibrillation and congestive heart failure (AF-CHF) trial

The atrial fibrillation and congestive heart failure (AF-CHF) trial

S62 Journal of Cardiac Failure Vol. 9 No. 5 Suppl. 2003 222 223 Effect of Angiotensin II Receptor Blockade, Candesartan, on the Ventricular Remodeli...

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S62 Journal of Cardiac Failure Vol. 9 No. 5 Suppl. 2003 222


Effect of Angiotensin II Receptor Blockade, Candesartan, on the Ventricular Remodeling after Myocardial Infarction: Comparison with Angiotensin Converting Enzyme Inhibitor Eiichi Geshi,1 Hiroshi Suzuki,1 Takatoshi Sato,1 Makoto Shoji,1 Yoshitaka Iso,1 Masayuki Shibata,1 Shinji Koba,1 Mikitaka Murakami,1 Kakashi Katagiri1—1Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

The Atrial Fibrillation and Congestive Heart Failure (AF-CHF) Trial Denis Roy,1 for the AF(CHF) Trial Investigators—1Medicine, Montreal Heart Institute, Montreal, QC, Canada

Background: Left ventricular remodeling occurring after acute myocardial infarction (AMI) is an important factor to define the prognosis of chronic phase of myocardial infarction. Although some of comparative studies related to the efficacy and tolerability of angiotensin II receptor blockade (ARB) and angiotensin converting enzyme inhibitor (ACEI) after onset of AMI have been reported in the recent large-scale clinical trials, cardiovascular protective benefits of these agents are still controversial. Purpose: We compared the effect of ARB, candesartan, to ACEIs on the left ventricular remodeling in the chronic phase after onset of AMI especially focused on the hemodynamic and neurohormonal parameters. Method: In fifty-six patients with first AMI who underwent successful coronary intervention, after the informed consent regarding to this study, they were divided into 2 groups at random: In candesartan group (C group, n ⫽ 31), candesartan (4 mg/day) was administered within 24 hours after admission and dosage was increased to 8 mg/day as possible. In ACEI group (A group, n ⫽ 25), any one of ACEIs (i.e.; enarapril, lisinopril, etc) were administered within 24 hours and dosages were increased to the maximum of clinical use. Each drug was continued until 6 months in each group and other medications such as beta-blockades, diuretics, nitrates were used without limitations. Left ventriculography was performed at prior to drug administration and at 6 months after AMI, and serum BNP and IL-6 concentrations were measured chronologically to 6 months after AMI. Results: There were no significant differences in peak CK levels, ejection fraction (EF) and left ventricular end-diastolic volume index (LVEDVI) on admission, and onset of congestive heart failure and re-hospitalization rate related to the cardiovascular events within 6 months. The % change of EF between on admission and 6 months was significantly larger in C group than in A group (p ⬍ 0.05). The % change of LVEDVI between on admission and 6 months was significantly lower in C group than in A group (p ⬍ 0.05), indicating the more suppressive effect of ventricular remodeling in C group. BNP at 6 months was significantly and negatively correlated to the EF at 6 months (p ⬍ 0.05). IL-6 levels were tended to be high in patients whose LVEDVI was increased at 6 months. Furthermore, serum BNP levels were significantly lower in C group than in A group (p ⬍ 0.05) and serum IL-6 levels were tended to be lower in C group than in A group at 6 months. Conclusion: These results indicated that angiotensin II receptor blockade, candesartan, is more effective to prevent left ventricular remodeling after AMI than angiotensin converting enzyme inhibitors especially in the both hemodynamic and neurohormonal parameters.

224 Levosimendan Treatment for Acutely Decompensated Heart Failure Is as Effective for Chagas Disease Patients as for Patients with Other Etiologies Antonio C.P. Barretto,1 Salvador Rassi,1 Fabio Vilas-Boas,1 Jorge P. Ribeiro,1 Denilson C. Albuquerque,1 Silvia G. Lage,1 Jader Baima1—1Prevention and Rehabilitation Cardiovascular Service, Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Sao Paulo, Brazil Background: The BELIEF study was designed to evaluate the safety and efficacy of a 24h-levosimendan (Levo) infusion for the treatment of acutely decompensated heart failure (HF) patients (pts). The primary endpoint was to check the proportion of pts who has been discharged from the hospital without need of using inotropes, other than Levo. In this subset, we investigated if the Chagas disease (CD) subgroup has had the same hemodynamics benefits and achieved the primary endpoint comparing with non-CD pts. Methods: The BELIEF study was a multicentric trial, in which 156 acutely decompensated NYHA class IV HF pts, mostly male (68%), mean of 56 years old, have received a 24-h Levo infusion of 0.05–0.2 mg/kg/min. The pts have been diagnosed with HF 6 years ago, with a mean of 2.99 hospitalizations within the past year. The initial systolic blood pressure (SBP) was 110.8 mmHg (70–180 mmHg). 28 pts (22.4%) had CD as the HF etiology, 42 were due to ischeamic disease and 38 were idiopathic. Results: 125 pts (78.6%) have achieved the primary endpoint. The same proportion was seen in the CD pts subset, when compared with the non-CD group (75% vs. 79.3%, p ⫽ 0.813). CD pts had the same mean age, sex distribution and clinical features as the non-Chagas pts. CD group had more frequently hypotension when compared to the non-CD group (28.5% vs. 15.4%, p ⫽ 0.0195). The dilated myocardiopathy group also had the same incidence of hypotension as the CD group (28.5% vs. 34.2%, p ⫽ 0.826). Conclusion: Chagas disease pts with acutely decompensated HF had the same hemodynamics benefits as HF pts with other etiologies treated with Levo. 3/4 of CD pts have been discharged from the hospital without the need of inotropes after Levo treatment. Although hypotension was slightly more frequent in the CD group, it did not reduce Levo response in this group of patients.

Nonrandomized studies suggest that atrial fibrillation (AF) is independently associated with increased mortality in heart failure patients. Whether restoring and maintaining sinus rhythm will have a beneficial impact on cardiovascular mortality in heart failure patients has never been tested in an adequately-powered randomized trial. The Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial is a prospective multicenter trial (130 centers in Canada, USA, South America, Europe, and Israel), that will randomize 1,450 congestive heart failure patients with left ventricular ejection fraction ⱕ35% and AF to one of two treatment strategies: 1) rhythm control with the use of electrical cardioversion combined with antiarrhythmic drugs (amiodarone or other class III agents), and additional nonpharmacologic therapy in resistant patients; 2) rate control with the use of beta-blockers, digoxin and/or pacemaker and AV nodal ablation. Enrollment began in May 2001 and is expected to end in 2004 with a minimum follow-up of 2 years. As of today 660 patients have been randomized. The mean age is 65 ⫾ 11 years, and 81% are male. Ischemic heart disease is the predominant diagnosis in 48% of patients and dilated cardiomyopathy is noted in 38% of patients. The mean left ventricular ejection fraction is 27 ⫾ 6%, AF is persistent in 66% of patients. Patients are optimally created with beta-blockers (80%), ACE inhibitors (87%) and oral anticoagulation (90%). Adherence to the assigned treatment strategy is maintained in over 90% of patients. Cardiovascular mortality is the primary endpoint. We anticipate a 18.75% 2-year cardiovascular mortality in the rate control arm with a 25% mortality reduction in the rhythm control group. The intentionto-treat approach will be the primary method of analyses.

225 A Prospective Study of Out-Patient Continuous Milrinone Therapy in Patients Awaiting Heart Transplant Susan Brozena,1 Carol Twomey,1 Lee Goldberg,1 Shashank Desai,1 Brian Drachman,1 Andrew Kao,1 Eric Popjes,1 Ross Zimmer,1 Mariell Jessup1— 1 Medicine, University of Pennsylvania, Philadelphia, PA Background: The potential deleterious effects of long-term continuous intravenous (IV) milrinone (M) therapy are unknown. We performed a prospective, non-randomized study to determine the feasibility and safety of continuous IVM therapy administered at home in patients (pts) who were inotrope-dependent and listed for heart transplant as Status IB. Methods: Pts could enter the study if they met specific criteria including clinically stable on effective dose of M ⱕ0.5 mcg/kg/min, presence of implantable cardioverter-defibrillator (ICD), and no other serious comorbidity. Informed consent was obtained. The primary endpoint was survival to transplant. Hospitalizations, arrhythmias, quality of life (QOL), and cost comparisons were assessed. Statistical analyses were performed using SAS version 6.12 software (SAS Institute North Carolina). Continuous variables are reported as mean ⫾ standard deviation. QOL data (Minnesota Living With Heart Failure score) were analyzed using twotailed student t-tests. Results: Over 43 months, 60 pts (51 men, 9 women), aged 55.5 ⫾ 8.4 yrs, entered the study. Ischemic heart disease was present in 66.6%; idiopathic dilated cardiomyopathy in 30.0%. Baseline values prior to listing for transplant: left ventricular ejection fraction 19.9 ⫾ 7.9%, peak oxygen consumption 11.4 ⫾ 2.6 ml/kg/min, cardiac index 1.94 ⫾ 0.63 l/min/m2. Mean dose of M was 0.33 ⫾ 0.1 mcg/kg/min. Pts were followed in the study for a mean of 160.1 ⫾ 151.8 days. Days to transplant varied according to blood type: 209.5 ⫾ 182 in 31 pts with type O; 125.0 ⫾ 78.1 in 17 pts with A; 50.4 ⫾ 37.8 in 5 pts with B. Table 1. Clinical outcomes Outcome Transplant as Status IB as Status IA Still waiting Died before transplant Removed from study & transplant list* Required biventricular assist device Required left ventricular assist device

# patients

% patients

53 30 23 3 2 2 2 1

88.3 56.6 43.4 5.0 3.3 3.3 3.3 1.6

*One removed for non-compliance; one for clinical improvement Fifty-three pts (88.3%) underwent transplant. There were two deaths, both due to heart failure (HF). During the study, two-thirds of the patients required at least one readmission for HF, 14 pts required no admission, 20 pts had no admission for HF but were admitted for other reasons (7 pts due to IV line infection requiring IV antibiotics; 7 for non-cardiac diagnoses; 3 for syncope; 2 for angina). Six pts had 9 admissions for tachyarrhythmias terminated by ICD firing, all but one episode was for ventricular tachycardia (VT). QOL score improved by ⫺13.3 ⫾ 22.2 at one month post-discharge from the hospital. (p ⫽ 0.0061) Home care charges were 4.2% of hospital charges. Conclusions: Continuous IVM therapy can be safely administered at home in selected patients with advanced HF who are listed for transplant, though re-hospitalization for HF is common. If not already present, we recommend ICD implantation prior to home discharge given the incidence of VT. Outcomes, QOL and cost savings are favorable. This strategy may be an acceptable and safe alternative to prolonged hospitalization in this group of patients.