Circulation: Journal of the American Heart Association最新文献_第9页

Long-Term Survival and Hemodynamics After Endothelin-A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition in Rats With Chronic Heart Failure: Monotherapy Versus Combination Therapy 慢性心力衰竭大鼠内皮素a受体拮抗剂和血管紧张素转换酶抑制后的长期生存和血流动力学:单一治疗与联合治疗

Circulation: Journal of the American Heart Association Pub Date : 2002-08-27 DOI: 10.1161/01.CIR.0000027138.07524.38

P. Mulder, H. Boujedaini, V. Richard, J. Henry, S. Renet, K. Münter, C. Thuillez

{"title":"Long-Term Survival and Hemodynamics After Endothelin-A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition in Rats With Chronic Heart Failure: Monotherapy Versus Combination Therapy","authors":"P. Mulder, H. Boujedaini, V. Richard, J. Henry, S. Renet, K. Münter, C. Thuillez","doi":"10.1161/01.CIR.0000027138.07524.38","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027138.07524.38","url":null,"abstract":"Background—In patients with congestive heart failure (CHF) receiving ACE inhibitors, acute administration of selective endothelin (ET) antagonists additionally improves systemic and cardiac hemodynamics. We investigated, in a rat model of CHF, whether such acute synergistic effects are sustained and accompanied, in the long term, by an additional limitation of left ventricular remodeling or an increase in survival. Methods and Results—Rats were subjected to coronary artery ligation and treated for 3 or 9 months with vehicle or with the ACE inhibitor trandolapril (Tr) (0.3 mg/kg−1 per day−1), the ETA antagonist LU 135252 (LU, 30 mg/kg−1 per day−1), or their combination starting 7 days after ligation. After 3 months, the combination decreased LV systolic- and end-diastolic pressures (−32% and −80%, respectively) more markedly than Tr (−21% and −61%, respectively) or LU alone (−14% and −48%, respectively). Echocardiographic studies revealed that all treatments limited LV dilatation and increased LV fractional shortening and cardiac index. All treatments equally reduced left ventricular collagen density, whereas only Tr or the combination reduced LV weight. Finally, although LU did not modify long-term survival, Tr and the combination of Tr with LU induced a similar improvement of survival. Conclusions—In this rat model, long-term combined administration of an ETA antagonist and an ACE inhibitor induces additional effects in terms of systemic and cardiac hemodynamics; however, this is not associated with an additional increase in long-term survival.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"13 1","pages":"1159-1164"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85008775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 43

Disproportionate Decrease in &agr;- Compared With &bgr;-Adrenergic Sensitivity in the Dorsal Hand Vein in Pregnancy Favors Vasodilation 与妊娠期手背静脉肾上腺素能敏感性相比，其不成比例的降低有利于血管舒张

Circulation: Journal of the American Heart Association Pub Date : 2002-08-27 DOI: 10.1161/01.CIR.0000028334.32833.B0

R. Landau, V. Dishy, A. Wood, C. Stein, R. Smiley

{"title":"Disproportionate Decrease in &agr;- Compared With &bgr;-Adrenergic Sensitivity in the Dorsal Hand Vein in Pregnancy Favors Vasodilation","authors":"R. Landau, V. Dishy, A. Wood, C. Stein, R. Smiley","doi":"10.1161/01.CIR.0000028334.32833.B0","DOIUrl":"https://doi.org/10.1161/01.CIR.0000028334.32833.B0","url":null,"abstract":"Background—Altered vascular responses to adrenergic agonists during pregnancy are thought to play an important role in the regulation of blood pressure and placental blood flow. Because &agr;1-adrenergic and &bgr;2-adrenergic sensitivity act in opposing directions to determine vascular tone, we simultaneously evaluated &agr;-adrenergic–mediated vasoconstriction and &bgr;-adrenergic–mediated vasodilation in dorsal hand veins during and after pregnancy. Methods and Results—Twenty healthy pregnant women were studied at 32 to 37 weeks of gestation and again 12 weeks after delivery. Vascular response to phenylephrine (PE) and isoproterenol (ISO) was measured in a dorsal hand vein using the linear variable differential transformer technique. The dose of PE resulting in 50% constriction (CD50) was determined. The response to ISO was measured after the PE preconstriction. Pregnant and postpartum values, expressed as geometric mean (95% CI), were compared by paired t test. &agr;-Adrenergic sensitivity during pregnancy (CD50 2.7 &mgr;g/min [95% CI, 1.5 to 5.0]) was markedly decreased, ≈7-fold, compared with postpartum (0.4 &mgr;g/min [95% CI, 0.3 to 0.7] [P <0.01]). &bgr;-Adrenergic vasodilation was also attenuated during pregnancy. The ED50 of ISO (dose of ISO resulting in 50% of the maximal response, Emax) was greater during pregnancy (20 ng/min [95% CI, 11 to 35]) than postpartum (8 ng/min [95% CI, 5 to 12]) (P <0.05). ISO Emax was also significantly less during pregnancy (81% [95% CI, 65 to 97] compared with postpartum (105% [95% CI, 97 to 113]) (P <01.01). Conclusions—Normal pregnancy is characterized by decreased venous sensitivity to both &agr;1-adrenoceptor–mediated vasoconstriction and &bgr;2-adrenoceptor–mediated vasodilation. The greater decrease in &agr;1 compared with &bgr;2 response may contribute to the vasodilated state characteristic of human pregnancy.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"1 1","pages":"1116-1120"},"PeriodicalIF":0.0,"publicationDate":"2002-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89379578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Elevated Levels of Oxidative DNA Damage and DNA Repair Enzymes in Human Atherosclerotic Plaques 人类动脉粥样硬化斑块中DNA氧化损伤和DNA修复酶水平升高

Circulation: Journal of the American Heart Association Pub Date : 2002-08-20 DOI: 10.1161/01.CIR.0000026393.47805.21

W. Martinet, M. Knaapen, G. D. De Meyer, A. Herman, M. Kockx

{"title":"Elevated Levels of Oxidative DNA Damage and DNA Repair Enzymes in Human Atherosclerotic Plaques","authors":"W. Martinet, M. Knaapen, G. D. De Meyer, A. Herman, M. Kockx","doi":"10.1161/01.CIR.0000026393.47805.21","DOIUrl":"https://doi.org/10.1161/01.CIR.0000026393.47805.21","url":null,"abstract":"Background—The formation of reactive oxygen species is a critical event in atherosclerosis because it promotes cell proliferation, hypertrophy, growth arrest, and/or apoptosis and oxidation of LDL. In the present study, we investigated whether reactive oxygen species-induced oxidative damage to DNA occurs in human atherosclerotic plaques and whether this is accompanied by the upregulation of DNA repair mechanisms. Methods and Results—We observed increased immunoreactivity against the oxidative DNA damage marker 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dG) in plaques of the carotid artery compared with the adjacent inner media and nonatherosclerotic mammary arteries. Strong 8-oxo-dG immunoreactivity was found in all cell types of the plaque including macrophages, smooth muscle cells, and endothelial cells. As shown by competitive ELISA, carotid plaques contained 160±29 8-oxo-dG residues/105 dG versus 3±1 8-oxo-dG residues/105 dG in mammary arteries. Single-cell gel electrophoresis showed elevated levels of DNA strand breaks in the plaque. The overall number of apoptotic nuclei was low (1% to 2%) and did not correlate with the amount of 8-oxo-dG immunoreactive cells (>90%). This suggests that initial damage to DNA occurs at a sublethal level. Several DNA repair systems that are involved in base excision repair (redox factor/AP endonuclease [Ref 1] and poly(ADP-ribose) polymerase 1 [PARP-1]) or nonspecific repair pathways (p53, DNA-dependent protein kinase) were upregulated, as shown by Western blotting and immunohistochemistry. Overexpression of DNA repair enzymes was associated with elevated levels of proliferating cell nuclear antigen. Conclusions—Our findings provide evidence that oxidative DNA damage and repair increase significantly in human atherosclerotic plaques.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"10 1","pages":"927-932"},"PeriodicalIF":0.0,"publicationDate":"2002-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84454697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 426

Exercise-Induced Increase in Baroreflex Sensitivity Predicts Improved Prognosis After Myocardial Infarction 运动诱导的压力反射敏感性的增加预示心肌梗死后预后的改善

Circulation: Journal of the American Heart Association Pub Date : 2002-08-20 DOI: 10.1161/01.CIR.0000027565.12764.E1

M. L. La Rovere, C. Bersano, M. Gnemmi, G. Specchia, P. Schwartz

{"title":"Exercise-Induced Increase in Baroreflex Sensitivity Predicts Improved Prognosis After Myocardial Infarction","authors":"M. L. La Rovere, C. Bersano, M. Gnemmi, G. Specchia, P. Schwartz","doi":"10.1161/01.CIR.0000027565.12764.E1","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027565.12764.E1","url":null,"abstract":"Background—Despite the rational expectation for a survival benefit produced by exercise training among post–myocardial infarction (MI) patients, direct evidence remains elusive. Clinically, changes in autonomic balance toward lower vagal activity have consistently been associated with increased mortality risk; conversely, among both control and post-MI dogs, exercise training improved vagal reflexes and prevented sudden death. Accordingly, we tested the hypothesis that exercise training, if accompanied by a shift toward increased vagal activity of an autonomic marker such as baroreflex sensitivity (BRS), could reduce mortality in post-MI patients. Methods and Results—Ninety-five consecutive male patients surviving a first uncomplicated MI were randomly assigned to a 4-week endurance training period or to no training. Age (51±8 versus 52±8 years), site of MI (anterior 41% versus 43%), left ventricular ejection fraction (52±13 versus 51±14%), and BRS (7.9±5.4 versus 7.9±3.4 ms/mm Hg) did not differ between the two groups. After 4 weeks, BRS improved by 26% (P =0.04) in trained patients, whereas it did not change in nontrained patients. During a 10-year follow-up, cardiac mortality among the 16 trained patients who had an exercise-induced increase in BRS ≥3 ms/mm Hg (responders) was strikingly lower compared with that of the trained patients without such a BRS increase (nonresponders) and that of the nontrained patients (0 of 16 versus 18 of 79 [23%], P =0.04). Cardiac mortality was also lower among responders irrespective of training (4% versus 24%, P =0.04). Conclusions—Post-MI exercise training can favorably modify long-term survival, provided that it is associated with a clear shift of the autonomic balance toward an increase in vagal activity.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"15 1","pages":"945-949"},"PeriodicalIF":0.0,"publicationDate":"2002-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90843910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 330

Prevention of Diabetes-Induced Microangiopathy by Human Tissue Kallikrein Gene Transfer 人组织激肽激酶基因转移预防糖尿病性微血管病变

Circulation: Journal of the American Heart Association Pub Date : 2002-08-20 DOI: 10.1161/01.CIR.0000027104.33206.C8

C. Emanueli, M. Salis, A. Pinna, Tiziana Stacca, A. Milia, A. Spano, J. Chao, L. Chao, L. Sciola, P. Madeddu

引用次数: 83

Smoking Is Associated With Altered Endothelial-Derived Fibrinolytic and Antithrombotic Factors: An In Vitro Demonstration 吸烟与内皮源性纤维蛋白溶解和抗血栓因子的改变有关:一项体外证明

Circulation: Journal of the American Heart Association Pub Date : 2002-08-20 DOI: 10.1161/01.cir.0000029091.61707.6b

Rajat S Barua, J. Ambrose, D. Saha, L. Eales-Reynolds

{"title":"Smoking Is Associated With Altered Endothelial-Derived Fibrinolytic and Antithrombotic Factors: An In Vitro Demonstration","authors":"Rajat S Barua, J. Ambrose, D. Saha, L. Eales-Reynolds","doi":"10.1161/01.cir.0000029091.61707.6b","DOIUrl":"https://doi.org/10.1161/01.cir.0000029091.61707.6b","url":null,"abstract":"Background—Data about the effects of smoking on thrombo-hemostatic factors (tissue factor [TF] and tissue factor pathway inhibitor [TFPI-1]) are limited and on fibrinolytic factors (tissue plasminogen activator [t-PA] and plasminogen activator inhibitor-1 [PAI-1]) are debatable. The present study investigated the smoking-related, endothelial cell (EC)–specific responses for these factors and their relation to nitric oxide (NO) production in vitro. Methods and Results—Serum from 8 nonsmokers and 15 smokers were incubated with confluent (≈85%) human umbilical vein endothelial cells (HUVECs) in 24-well tissue-culture plates for 12 hours. After the incubation, basal NO, t-PA, PAI-1, TF, TFPI-1 production, and substance P (SP)–stimulated NO, t-PA, and PAI-1 production were determined. HUVECs treated with smokers’ serum showed lower basal (P <0.02) and SP-stimulated (P =0.059) t-PA production but similar basal and stimulated PAI-1 production (P =0.9 and P =0.6) compared with nonsmokers. Basal t-PA/PAI-1 molar ratio was significantly reduced in smokers (P <0.005). TFPI-1 level in the cell culture supernatant was also significantly lower in smokers compared with the nonsmoker group (P <0.05) with no difference in TF level between both groups (P =0.5). As previously reported, both basal (P <0.001) and SP-stimulated (P <0.05) NO production were significantly reduced in smokers. Basal TFPI-1 in culture correlated positively with basal NO production (r =0.42, P =0.04) and negatively with serum cotinine level (r =−0.6, P =0.01). Conclusions—These results indicate that cigarette smoking is associated with alterations in EC-derived fibrinolytic (t-PA) and antithrombotic (TFPI-1) factors. To our knowledge, this is the first demonstration that EC-derived TFPI is affected by smoking and endogenous NO or that the degree of smoke exposure may influence TFPI levels in an EC milieu.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"17 1","pages":"905-908"},"PeriodicalIF":0.0,"publicationDate":"2002-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81927495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 106

Prognostic Implications of Abnormalities in Renal Function in Patients With Acute Coronary Syndromes 急性冠脉综合征患者肾功能异常对预后的影响

Circulation: Journal of the American Heart Association Pub Date : 2002-08-20 DOI: 10.1161/01.CIR.0000027560.41358.B3

J. Al Suwaidi, D. Reddan, K. Williams, K. Pieper, R. Harrington, R. Califf, C. Granger, E. Ohman, D. Holmes

{"title":"Prognostic Implications of Abnormalities in Renal Function in Patients With Acute Coronary Syndromes","authors":"J. Al Suwaidi, D. Reddan, K. Williams, K. Pieper, R. Harrington, R. Califf, C. Granger, E. Ohman, D. Holmes","doi":"10.1161/01.CIR.0000027560.41358.B3","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027560.41358.B3","url":null,"abstract":"Background—Outcomes in patients with mild to moderate renal function (RF) abnormalities presenting with acute coronary syndromes (ACS) are not well defined. Methods and Results—A convenience sample of 4 ACS trial databases including all enrolled patients was assessed to determine 30- and 180-day outcomes. The 4 trials were Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb, GUSTO-III, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON-A). Patients were stratified into ST-segment elevation (STE) and non–ST-segment elevation (NSE) groups and by the presence or absence of abnormal RF (creatinine clearance <70 mL/min). In the STE group, 7670 of 18 621 patients (41%) had abnormal RF. In the NSE group, 8152 of 19 304 (42%) had abnormal RF. Patients with abnormal RF were older, more often female, and more likely to have adverse baseline characteristics. They had higher mortality and higher mortality/nonfatal myocardial infarction (MI) at both 30 and 180 days, regardless of ST-segment status. Creatinine clearance was independently associated with risk of mortality (hazard ratio 0.79 in the STE group and 0.81 in the NSE group) and with risk of mortality/MI (hazard ratio 0.93) in the NSE group at 180 days. Conclusions—Patients presenting with ACS frequently have abnormal RF. Abnormal RF is a marker of adverse baseline clinical characteristics and is independently associated with increased risk of death and death/MI.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"299 1","pages":"974-980"},"PeriodicalIF":0.0,"publicationDate":"2002-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79584866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 491

Low Serum Insulin-Like Growth Factor I Is Associated With Increased Risk of Ischemic Heart Disease: A Population-Based Case-Control Study 低血清胰岛素样生长因子I与缺血性心脏病风险增加相关:一项基于人群的病例对照研究

Circulation: Journal of the American Heart Association Pub Date : 2002-08-20 DOI: 10.1161/01.CIR.0000027563.44593.CC

A. Juul, T. Scheike, M. Davidsen, J. Gyllenborg, T. Jørgensen

{"title":"Low Serum Insulin-Like Growth Factor I Is Associated With Increased Risk of Ischemic Heart Disease: A Population-Based Case-Control Study","authors":"A. Juul, T. Scheike, M. Davidsen, J. Gyllenborg, T. Jørgensen","doi":"10.1161/01.CIR.0000027563.44593.CC","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027563.44593.CC","url":null,"abstract":"Background—Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis. We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of ischemic heart disease (IHD). Methods and Results—We conducted a nested case-control study within a large prospective study on cardiovascular epidemiology (DAN-MONICA). We measured IGF-I and IGFBP-3 in serum from 231 individuals who had a diagnosis of IHD 7.63 years after blood sampling and among 374 control subjects matched for age, sex, and calendar time. At baseline when all individuals were free of disease, subjects in the low IGF-I quartile had significantly higher risk of IHD during the 15-year follow-up period, with a relative risk (RR) of 1.94 (95% CI, 1.03 to 3.66) of IHD compared with the high IGF-I quartile group, when IGFBP-3, body mass index, smoking, menopause, diabetes, and use of antihypertensives were controlled for. Conversely, individuals in the high IGFBP-3 quartile group had an adjusted RR of 2.16 (95% CI, 1.18 to 3.95) of having IHD. Identification of a high-risk population with low IGF-I and high IGFBP-3 levels resulted in markedly higher risk of IHD (RR 4.07; 95% CI, 1.48 to 11.22) compared with the index group. Conclusions—Individuals without IHD but with low circulating IGF-I levels and high IGFBP-3 levels have significantly increased risk of developing IHD during a 15-year follow-up period. Our findings suggest that IGF-I may be involved in the pathogenesis of IHD.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"11 1","pages":"939-944"},"PeriodicalIF":0.0,"publicationDate":"2002-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88637130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 616

Mapping and Ablation of Idiopathic Ventricular Fibrillation 特发性心室颤动的定位和消融

Circulation: Journal of the American Heart Association Pub Date : 2002-08-20 DOI: 10.1161/01.CIR.0000027564.55739.B1

M. Haïssaguerre, M. Shoda, P. Jaïs, A. Nogami, D. Shah, J. Kautzner, T. Arentz, Dietrich Kalushe, D. Lamaison, Mike Griffith, F. Cruz, Â. D. de Paola, Fiorenzo Gaïta, M. Hocini, S. Garrigue, L. Macle, R. Weerasooriya, J. Clémenty

{"title":"Mapping and Ablation of Idiopathic Ventricular Fibrillation","authors":"M. Haïssaguerre, M. Shoda, P. Jaïs, A. Nogami, D. Shah, J. Kautzner, T. Arentz, Dietrich Kalushe, D. Lamaison, Mike Griffith, F. Cruz, Â. D. de Paola, Fiorenzo Gaïta, M. Hocini, S. Garrigue, L. Macle, R. Weerasooriya, J. Clémenty","doi":"10.1161/01.CIR.0000027564.55739.B1","DOIUrl":"https://doi.org/10.1161/01.CIR.0000027564.55739.B1","url":null,"abstract":"Background—Ventricular fibrillation is the main mechanism of sudden cardiac death. The feasibility of eliminating recurrent episodes by catheter ablation has not been reported. Methods and Results—Twenty-seven patients without known heart disease (13 men, 14 women, 41±14 years of age) were studied after being resuscitated from recurrent (10±12) episodes of primary idiopathic ventricular fibrillation; 23 had received a defibrillator. The first initiating beat of ventricular fibrillation had an identical electrocardiographic morphology and coupling interval (297±41 ms) to preceding isolated premature beats typically noted in the aftermath of resuscitation. These triggers were localized by mapping the earliest electrical activity and ablated by local radiofrequency delivery. Outcome was assessed by Holter and defibrillator memory interrogation. Premature beats were elicited from the Purkinje conducting system in 23 patients: from the left ventricular septum in 10, from the anterior right ventricle in 9, and from both in 4. The interval from the Purkinje potential to the following myocardial activation varied from 10 to 150 ms during premature beat but was 11±5 ms during sinus rhythm, indicating location at peripheral Purkinje arborization. The premature beats originated from the right ventricular outflow tract muscle in 4 patients. The accuracy of mapping was confirmed by acute elimination of premature beats during local radiofrequency delivery. During a follow-up of 24±28 months, 24 patients (89%) had no recurrence of ventricular fibrillation without drug. Conclusions—Primary idiopathic ventricular fibrillation is a syndrome characterized by dominant triggers from the distal Purkinje system. These sources can be eliminated by focal energy delivery.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"25 1","pages":"962-967"},"PeriodicalIF":0.0,"publicationDate":"2002-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84849363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 406

Comparison of Omapatrilat and Enalapril in Patients With Chronic Heart Failure: The Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE) Omapatrilat和依那普利在慢性心力衰竭患者中的比较:Omapatrilat与依那普利减少事件效用的随机试验(OVERTURE)

Circulation: Journal of the American Heart Association Pub Date : 2002-08-20 DOI: 10.1161/01.CIR.0000029801.86489.50

M. Packer, R. Califf, M. Konstam, H. Krum, J. McMurray, J. Rouleau, K. Swedberg

{"title":"Comparison of Omapatrilat and Enalapril in Patients With Chronic Heart Failure: The Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE)","authors":"M. Packer, R. Califf, M. Konstam, H. Krum, J. McMurray, J. Rouleau, K. Swedberg","doi":"10.1161/01.CIR.0000029801.86489.50","DOIUrl":"https://doi.org/10.1161/01.CIR.0000029801.86489.50","url":null,"abstract":"Background—Combined inhibition of the angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) may produce greater benefits in heart failure than ACE inhibition alone. Methods and Results—We randomly assigned 5770 patients with New York Heart Association class II to IV heart failure to double-blind treatment with either the ACE inhibitor enalapril (10 mg BID, n=2884) or to the ACE-NEP inhibitor omapatrilat (40 mg once daily, n=2886) for a mean of 14.5 months. The primary end point—the combined risk of death or hospitalization for heart failure requiring intravenous treatment—was used prospectively to test both a superiority and noninferiority hypothesis (based on the effect of enalapril in the Studies of Left Ventricular Dysfunction [SOLVD] Treatment Trial). A primary end point was achieved in 973 patients in the enalapril group and in 914 patients in the omapatrilat group (hazard ratio 0.94; 95% CI: 0.86 to 1.03, P =0.187)—a result that fulfilled prespecified criteria for noninferiority but not for superiority. The omapatrilat group also had a 9% lower risk of cardiovascular death or hospitalization (P =0.024) and a 6% lower risk of death (P =0.339). Post hoc analysis of the primary end point with the definition used in the SOLVD Treatment Trial (which included all hospitalizations for heart failure) showed an 11% lower risk in patients treated with omapatrilat (nominal P =0.012). Conclusion—Omapatrilat reduces the risk of death and hospitalization in chronic heart failure but was not more effective than ACE inhibition alone in reducing the risk of a primary clinical event. Between-group differences in favor of omapatrilat observed in secondary and post hoc analyses warrant further study.","PeriodicalId":10194,"journal":{"name":"Circulation: Journal of the American Heart Association","volume":"1 1","pages":"920-926"},"PeriodicalIF":0.0,"publicationDate":"2002-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89578840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 633