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A New Strategy for the Management of Atrial Fibrillation in Heart Failure Patients ∼Prospects for Atrial-selective Anti-AF Agent
S146 Journal of Cardiac Failure Vol. 15 No. 7S September 2009
Symposium 8 S8-1 Current Status of Congestive Heart Failure With Atrial Fibrillation: From Shinken Database TAKESHI YAMASHITA The Cardiovascular Institute Atrial fibrillation (AF) has been believed to be associated with poor prognosis in congestive heart failure (CHF). Actually, SOLVD data has demonstrated that CHF patients with AF showed higher mortality than those without AF. However, the data were derived from a clinical study performed in Western countries before 2000. Therefore, to stratify treatment for CHF with AF at present, we should know the current status of Japanese CHF patients with AF. Shinken Database was conducted to investigate the mortality and morbidity of cardiovascular diseases in Japan. The database comprises details on all of the new patients, including both inpatients and outpatients, who visited The Cardiovascular Institute Hospital between April 2004 and March 2006 (n 5 6562). In this hospital-based cohort, 891 patients were with CHF (260 with AF and 631 with sinus rhythm). In this symposium, we will compare the patient characteristics and mortality between patients with and without AF. Our data will reveal that simple association of AF with poor prognosis should be reevaluated in the real world practice in Japan.
S8-2 A New Strategy for the Management of Atrial Fibrillation in Heart Failure Patients wProspects for Atrial-selective Anti-AF Agent SATOSHI OGAWA International University of Health and Welfare, Mita Hospital None of the anti-arrhyhtmic agents currently available are ideal in the sense that they are capable of curing AF effectively and safely, and the development of new agents, including atrial-selective ant-AF agents, is greatly anticipated. It is hoped that such agents will be less likely to induce heart failure and weaker ventricular proarrhythmic actions than conventional drugs and can be administerd safely to heart failure patients. Under these circumstances, novel anti-arrhythmic agents that selectively act on ion channels expressed atrium-specifically, have no effect on the ventricles, do not prolong the QT interval or QRS interval, and have no proarrythmia or negative inotropic actions, have recently been attracting attention. The results of a phase 3 study of intravenous vernakalant, which is one of atrial-selective agents, were released last year, and revealed a high conversion rate of 37.6% for 336 patients with paroxysmal and persistent AF. NTC-801 is a novel, selective Ik.Ach blocker. It prolongs the refractory period of atrial myocardium and shows promise as an anti-AF drug. NTC-801 is very promising in terms of efficacy for the treatment of vagally-mediated atrial fibrillation, but there is also a basis for expecting it to be effective against other pathology, especially AF in heart failure patients. The results of a phase 2 clinical study that will begin this summer are being awaited.
S8-3 Up-stream Therapy for Atrial Fibrillation in Patients With Heart Failure SHINICHI NIWANO Department of Cardio-Angiology, Kitasato University School of Medicine, Sagamihara, Japan Background: The use of antiarrhythmic agents would be limited in heart failure (HF) patients because of their negative inotropic action. The effects of therapies for HF were evaluated as up-stream therapies for AF in HF patients. Methods: The study subject consisted of 266 consecutive patients with history of hospitalization due to HF (ONYHA-III) but without documented AF were followed-up under pharmacological therapies for HF. The incidence of new onset AF was evaluated and predicting factors for the appearance of AF were evaluated by univariate and multivariate analyses. Results: During the observation period of 15 6 7 (6-36) months, 38/266 patients exhibited new onset AF. In those patients with AF, BNP level was higher (p 5 0.008), LVEF was lower (p 5 0.042), incidence of use of ARB/ACEI, betablocker or spironolactone was lower (p 5 0.002, p 5 0.039, p 5 0.041) in comparison with patients without AF in univariate analysis. In the multivariate analysis, only BNP level O 200 pg/ml and no-use of ARB/ACEI were the independent predicting factors for new onset AF (p 5 0.043, p 5 0.013). In Kaplan-Meier analysis, the incidence of AF was higher in patients with BNP O 200 pg/ml (n 5 93) than the others (n 5 173, p 5 0.021) and lower in patients with ARB/ACEI use (n 5 200) than the others (n 5 66, p 5 0.0005). Conclusion: In patients with history of
hospitalization due to HF, use of ARB/ACEI was considered effective for prevention of AF as up-stream therapy.
S8-4 Ablation Therapy of Atrial Fibrillation in Heart Failure KOICHIRO KUMAGAI Heart Rhythm Center, Fukuoka Sanno Hospital Congestive heart failure and atrial fibrillation (AF) often coexist, and each adversely affects the other with respect to management and prognosis. Evidence from the AFFIRM investigators highlights the potential benefit of maintaining sinus rhythm if it could be achieved without the adverse effects of antiarrhythmic drugs. Catheter ablation for AF has been established as an effective therapeutic option for AF that is resistant to pharmacologic rhythm or rate control, with successful long-term maintenance of sinus rhythm in the absence of treatment with antiarrhythmic drugs reported in the majority of patients. Though the results of catheter ablation have been improving, with the success rate reported as more than 80% for paroxysmal AF, ablation of chronic AF has been more difficult and has required more extensive ablation. The results can be expected to improve with a better understanding of the substrate maintaining AF and with the development of more effective techniques. Curative ablation of AF offers the unique opportunity to maintain sinus rhythm without antiarrhythmic drugs, which can have deleterious effects. Several studies have demonstrated that restoration and maintenance of sinus rhythm by catheter ablation without the use of drugs in patients with heart failure and AF improve cardiac function, symptoms, exercise capacity, and quality of life.
S8-5 Anti-thrombotic Therapy for Heart Failure Patients With Atrial Fibrillation YUKIHIRO KORETSUNE Director, The Institute for Clinical Research, National Hospital Orgnization, Osaka National Hospital Congestive heart failure is one of the risk factor for ischemic stroke in patients with atrial fibrillation (AF), which is included in CHADS2 score as a one point. Although ACC/AHA/ESC guidelines for the treatment of AF allow to use aspirin for CHADS2 socre 1, the Japanese guideline 2008 did not accept aspirin as one of the first line therapy. The reason to exclude aspirin from the first line is from the Japanese evidence (JAST study) that aspirin is not effective to prevent ischemic stroke and substantially increase major bleeding in patients with a low to moderate risk of stroke. The precise mechanism in not clear why the congestive heart failure is a risk of stroke, however, several possibilities can be considered. With heart failure, diastolic dysfunction may impair left ventricular suction from the left atrium. It may increase the retention of flow in the left atrium. The increase in heart rate with heart failure may also impair diastolic function. Therapies for AF, such as diuretics, may increase blood coagulability. If the congestive heart failure is induced by tachycardia, and the rate control therapy improve the cardiac function, we may stop the anti-coagulant therapy with careful follow up for heart failure.
Symposium 8 S8-1 Current Status of Congestive Heart Failure With Atrial Fibrillation: From Shinken Database TAKESHI YAMASHITA The Cardiovascular Institute Atrial fibrillation (AF) has been believed to be associated with poor prognosis in congestive heart failure (CHF). Actually, SOLVD data has demonstrated that CHF patients with AF showed higher mortality than those without AF. However, the data were derived from a clinical study performed in Western countries before 2000. Therefore, to stratify treatment for CHF with AF at present, we should know the current status of Japanese CHF patients with AF. Shinken Database was conducted to investigate the mortality and morbidity of cardiovascular diseases in Japan. The database comprises details on all of the new patients, including both inpatients and outpatients, who visited The Cardiovascular Institute Hospital between April 2004 and March 2006 (n 5 6562). In this hospital-based cohort, 891 patients were with CHF (260 with AF and 631 with sinus rhythm). In this symposium, we will compare the patient characteristics and mortality between patients with and without AF. Our data will reveal that simple association of AF with poor prognosis should be reevaluated in the real world practice in Japan.
S8-2 A New Strategy for the Management of Atrial Fibrillation in Heart Failure Patients wProspects for Atrial-selective Anti-AF Agent SATOSHI OGAWA International University of Health and Welfare, Mita Hospital None of the anti-arrhyhtmic agents currently available are ideal in the sense that they are capable of curing AF effectively and safely, and the development of new agents, including atrial-selective ant-AF agents, is greatly anticipated. It is hoped that such agents will be less likely to induce heart failure and weaker ventricular proarrhythmic actions than conventional drugs and can be administerd safely to heart failure patients. Under these circumstances, novel anti-arrhythmic agents that selectively act on ion channels expressed atrium-specifically, have no effect on the ventricles, do not prolong the QT interval or QRS interval, and have no proarrythmia or negative inotropic actions, have recently been attracting attention. The results of a phase 3 study of intravenous vernakalant, which is one of atrial-selective agents, were released last year, and revealed a high conversion rate of 37.6% for 336 patients with paroxysmal and persistent AF. NTC-801 is a novel, selective Ik.Ach blocker. It prolongs the refractory period of atrial myocardium and shows promise as an anti-AF drug. NTC-801 is very promising in terms of efficacy for the treatment of vagally-mediated atrial fibrillation, but there is also a basis for expecting it to be effective against other pathology, especially AF in heart failure patients. The results of a phase 2 clinical study that will begin this summer are being awaited.
S8-3 Up-stream Therapy for Atrial Fibrillation in Patients With Heart Failure SHINICHI NIWANO Department of Cardio-Angiology, Kitasato University School of Medicine, Sagamihara, Japan Background: The use of antiarrhythmic agents would be limited in heart failure (HF) patients because of their negative inotropic action. The effects of therapies for HF were evaluated as up-stream therapies for AF in HF patients. Methods: The study subject consisted of 266 consecutive patients with history of hospitalization due to HF (ONYHA-III) but without documented AF were followed-up under pharmacological therapies for HF. The incidence of new onset AF was evaluated and predicting factors for the appearance of AF were evaluated by univariate and multivariate analyses. Results: During the observation period of 15 6 7 (6-36) months, 38/266 patients exhibited new onset AF. In those patients with AF, BNP level was higher (p 5 0.008), LVEF was lower (p 5 0.042), incidence of use of ARB/ACEI, betablocker or spironolactone was lower (p 5 0.002, p 5 0.039, p 5 0.041) in comparison with patients without AF in univariate analysis. In the multivariate analysis, only BNP level O 200 pg/ml and no-use of ARB/ACEI were the independent predicting factors for new onset AF (p 5 0.043, p 5 0.013). In Kaplan-Meier analysis, the incidence of AF was higher in patients with BNP O 200 pg/ml (n 5 93) than the others (n 5 173, p 5 0.021) and lower in patients with ARB/ACEI use (n 5 200) than the others (n 5 66, p 5 0.0005). Conclusion: In patients with history of
hospitalization due to HF, use of ARB/ACEI was considered effective for prevention of AF as up-stream therapy.
S8-4 Ablation Therapy of Atrial Fibrillation in Heart Failure KOICHIRO KUMAGAI Heart Rhythm Center, Fukuoka Sanno Hospital Congestive heart failure and atrial fibrillation (AF) often coexist, and each adversely affects the other with respect to management and prognosis. Evidence from the AFFIRM investigators highlights the potential benefit of maintaining sinus rhythm if it could be achieved without the adverse effects of antiarrhythmic drugs. Catheter ablation for AF has been established as an effective therapeutic option for AF that is resistant to pharmacologic rhythm or rate control, with successful long-term maintenance of sinus rhythm in the absence of treatment with antiarrhythmic drugs reported in the majority of patients. Though the results of catheter ablation have been improving, with the success rate reported as more than 80% for paroxysmal AF, ablation of chronic AF has been more difficult and has required more extensive ablation. The results can be expected to improve with a better understanding of the substrate maintaining AF and with the development of more effective techniques. Curative ablation of AF offers the unique opportunity to maintain sinus rhythm without antiarrhythmic drugs, which can have deleterious effects. Several studies have demonstrated that restoration and maintenance of sinus rhythm by catheter ablation without the use of drugs in patients with heart failure and AF improve cardiac function, symptoms, exercise capacity, and quality of life.
S8-5 Anti-thrombotic Therapy for Heart Failure Patients With Atrial Fibrillation YUKIHIRO KORETSUNE Director, The Institute for Clinical Research, National Hospital Orgnization, Osaka National Hospital Congestive heart failure is one of the risk factor for ischemic stroke in patients with atrial fibrillation (AF), which is included in CHADS2 score as a one point. Although ACC/AHA/ESC guidelines for the treatment of AF allow to use aspirin for CHADS2 socre 1, the Japanese guideline 2008 did not accept aspirin as one of the first line therapy. The reason to exclude aspirin from the first line is from the Japanese evidence (JAST study) that aspirin is not effective to prevent ischemic stroke and substantially increase major bleeding in patients with a low to moderate risk of stroke. The precise mechanism in not clear why the congestive heart failure is a risk of stroke, however, several possibilities can be considered. With heart failure, diastolic dysfunction may impair left ventricular suction from the left atrium. It may increase the retention of flow in the left atrium. The increase in heart rate with heart failure may also impair diastolic function. Therapies for AF, such as diuretics, may increase blood coagulability. If the congestive heart failure is induced by tachycardia, and the rate control therapy improve the cardiac function, we may stop the anti-coagulant therapy with careful follow up for heart failure.