The Experts below are selected from a list of 135 Experts worldwide ranked by ideXlab platform
Mary A. Whooley - One of the best experts on this subject based on the ideXlab platform.
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first degree atrioventricular block is associated with heart failure and death in persons with stable coronary artery disease data from the heart and soul study
European Heart Journal, 2011Co-Authors: Ryan K. Crisel, Mary A. Whooley, Ramin FarzanehfarAbstract:Aims First-degree atrioventricular block (AVB) has traditionally been considered a benign Electrocardiographic Finding in healthy individuals. However, the clinical significance of first-degree AVB has not been evaluated in patients with stable coronary heart disease. We investigated whether first-degree AVB is associated with heart failure (HF) and mortality in a prospective cohort study of outpatients with stable coronary artery disease (CAD). Methods and results We measured the P–R interval in 938 patients with stable CAD and classified them into those with (P–R interval ≥220 ms) and without (P–R interval <220 ms) first-degree AVB. Hazard ratios (HRs) and 95% confidence intervals were calculated for HF hospitalization and all-cause mortality. During 5 years of follow-up, there were 123 hospitalizations for HF and 285 deaths. Compared with patients who had normal atrioventricular conduction, those with first-degree AVB were at increased risk for HF hospitalization (age-adjusted HR 2.33: 95% CI 1.49–3.65; P = 0.0002), mortality [age-adjusted HR 1.58; 95% CI (1.13–2.20); P = 0.008], cardiovascular (CV) mortality [age-adjusted HR 2.33; 95% CI (1.28–4.22); P = 0.005], and the combined endpoint of HF hospitalization or CV mortality (age-adjusted HR 2.43: 95% CI 1.64–3.61; P ≤ 0.0001). These associations persisted after multivariable adjustment for heart rate, medication use, ischaemic burden, and QRS duration. Adjustment for left ventricular systolic and diastolic function partially attenuated the effect, but first-degree AVB remained associated with the combined endpoint of HF or CV death (HR 1.61, CI 1.02–2.54; P = 0.04). Conclusion In a large cohort of patients with stable coronary artery disease, first-degree AVB is associated with HF and death.
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First-degree atrioventricular block is associated with heart failure and death in persons with stable coronary artery disease: data from the Heart and Soul Study
European heart journal, 2011Co-Authors: Ryan K. Crisel, Ramin Farzaneh-far, Mary A. WhooleyAbstract:Aims First-degree atrioventricular block (AVB) has traditionally been considered a benign Electrocardiographic Finding in healthy individuals. However, the clinical significance of first-degree AVB has not been evaluated in patients with stable coronary heart disease. We investigated whether first-degree AVB is associated with heart failure (HF) and mortality in a prospective cohort study of outpatients with stable coronary artery disease (CAD). Methods and results We measured the P–R interval in 938 patients with stable CAD and classified them into those with (P–R interval ≥220 ms) and without (P–R interval
George H Talbot - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics and safety of cxa 101 a new antipseudomonal cephalosporin in healthy adult male and female subjects receiving single and multiple dose intravenous infusions
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Yigong Ge, M J Whitehouse, Ian R Friedland, George H TalbotAbstract:CXA-101 is a novel, broad-spectrum cephalosporin with excellent antipseudomonal activity. A Phase 1 study was performed to determine the safety, tolerability, and pharmacokinetics of CXA-101 after single- and multiple-dose intravenous administration over 1 h to healthy male and female subjects. In part 1 of the study, five cohorts of eight subjects each (six receiving CXA-101 and two receiving a placebo) received single ascending doses of 250, 500, 1,000, 1,500, and 2,000 mg. In part 2, cohorts 1 and 2 received 500 mg and 1,000 mg, respectively, every 8 h, and cohort 3 received 1,500 mg every 12 h; each cohort received dosing for 10 days. Standard safety and tolerability assessments were performed. Blood and urine pharmacokinetic samples were assayed by a validated bioanalytical method and analyzed using standard noncompartmental methodology. All 64 subjects completed dosing; none withdrew from the study. Drug-related systemic adverse events were infrequent and mild. Mild, non-treatment-limiting infusion site events occurred during multiple-dose administration. No clinically significant laboratory or Electrocardiographic Finding or dose-limiting toxicity was observed. CXA-101 exhibited dose-linear pharmacokinetics; the mean plasma half-life was ∼2.3 h. More than 90% of the administered dose was eliminated unchanged through renal excretion. In summary, CXA-101 administered as a 1-hour infusion was generally safe and well tolerated in single doses up to 2,000 mg and in multiple doses up to 3 g daily over 10 days. The favorable safety and predictable pharmacokinetic profile of CXA-101 support its continuing clinical development for the treatment of serious bacterial infections.
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pharmacokinetics and safety of cxa 101 a new antipseudomonal cephalosporin in healthy adult male and female subjects receiving single and multiple dose intravenous infusions
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: M J Whitehouse, Ian R Friedland, George H TalbotAbstract:CXA-101 is a novel, broad-spectrum cephalosporin with excellent antipseudomonal activity. A Phase 1 study was performed to determine the safety, tolerability, and pharmacokinetics of CXA-101 after single- and multiple-dose intravenous administration over 1 h to healthy male and female subjects. In part 1 of the study, five cohorts of eight subjects each (six receiving CXA-101 and two receiving a placebo) received single ascending doses of 250, 500, 1,000, 1,500, and 2,000 mg. In part 2, cohorts 1 and 2 received 500 mg and 1,000 mg, respectively, every 8 h, and cohort 3 received 1,500 mg every 12 h; each cohort received dosing for 10 days. Standard safety and tolerability assessments were performed. Blood and urine pharmacokinetic samples were assayed by a validated bioanalytical method and analyzed using standard noncompartmental methodology. All 64 subjects completed dosing; none withdrew from the study. Drug-related systemic adverse events were infrequent and mild. Mild, non-treatment-limiting infusion site events occurred during multiple-dose administration. No clinically significant laboratory or Electrocardiographic Finding or dose-limiting toxicity was observed. CXA-101 exhibited dose-linear pharmacokinetics; the mean plasma half-life was approximately 2.3 h. More than 90% of the administered dose was eliminated unchanged through renal excretion. In summary, CXA-101 administered as a 1-hour infusion was generally safe and well tolerated in single doses up to 2,000 mg and in multiple doses up to 3 g daily over 10 days. The favorable safety and predictable pharmacokinetic profile of CXA-101 support its continuing clinical development for the treatment of serious bacterial infections.
Ryan K. Crisel - One of the best experts on this subject based on the ideXlab platform.
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first degree atrioventricular block is associated with heart failure and death in persons with stable coronary artery disease data from the heart and soul study
European Heart Journal, 2011Co-Authors: Ryan K. Crisel, Mary A. Whooley, Ramin FarzanehfarAbstract:Aims First-degree atrioventricular block (AVB) has traditionally been considered a benign Electrocardiographic Finding in healthy individuals. However, the clinical significance of first-degree AVB has not been evaluated in patients with stable coronary heart disease. We investigated whether first-degree AVB is associated with heart failure (HF) and mortality in a prospective cohort study of outpatients with stable coronary artery disease (CAD). Methods and results We measured the P–R interval in 938 patients with stable CAD and classified them into those with (P–R interval ≥220 ms) and without (P–R interval <220 ms) first-degree AVB. Hazard ratios (HRs) and 95% confidence intervals were calculated for HF hospitalization and all-cause mortality. During 5 years of follow-up, there were 123 hospitalizations for HF and 285 deaths. Compared with patients who had normal atrioventricular conduction, those with first-degree AVB were at increased risk for HF hospitalization (age-adjusted HR 2.33: 95% CI 1.49–3.65; P = 0.0002), mortality [age-adjusted HR 1.58; 95% CI (1.13–2.20); P = 0.008], cardiovascular (CV) mortality [age-adjusted HR 2.33; 95% CI (1.28–4.22); P = 0.005], and the combined endpoint of HF hospitalization or CV mortality (age-adjusted HR 2.43: 95% CI 1.64–3.61; P ≤ 0.0001). These associations persisted after multivariable adjustment for heart rate, medication use, ischaemic burden, and QRS duration. Adjustment for left ventricular systolic and diastolic function partially attenuated the effect, but first-degree AVB remained associated with the combined endpoint of HF or CV death (HR 1.61, CI 1.02–2.54; P = 0.04). Conclusion In a large cohort of patients with stable coronary artery disease, first-degree AVB is associated with HF and death.
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First-degree atrioventricular block is associated with heart failure and death in persons with stable coronary artery disease: data from the Heart and Soul Study
European heart journal, 2011Co-Authors: Ryan K. Crisel, Ramin Farzaneh-far, Mary A. WhooleyAbstract:Aims First-degree atrioventricular block (AVB) has traditionally been considered a benign Electrocardiographic Finding in healthy individuals. However, the clinical significance of first-degree AVB has not been evaluated in patients with stable coronary heart disease. We investigated whether first-degree AVB is associated with heart failure (HF) and mortality in a prospective cohort study of outpatients with stable coronary artery disease (CAD). Methods and results We measured the P–R interval in 938 patients with stable CAD and classified them into those with (P–R interval ≥220 ms) and without (P–R interval
Michel Haïssaguerre - One of the best experts on this subject based on the ideXlab platform.
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sudden cardiac arrest associated with early repolarization
The New England Journal of Medicine, 2008Co-Authors: Michel Haïssaguerre, Sinikka Ylimayry, Dominique Babuty, Jean-luc Pasquié, Akihiko Nogami, Isabel Deisenhofer, Nicolas Derval, Laurence Jesel, Christian De ChillouAbstract:Background: Early repolarization is a common Electrocardiographic Finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest. Methods: We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of Electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects. Results: Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (+/-SD) follow-up of 61+/-50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008). Conclusions: Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.
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Sudden Cardiac Arrest Associated with Early Repolarization
The New England Journal of Medicine, 2008Co-Authors: Michel Haïssaguerre, Dominique Babuty, Jean-luc Pasquié, Akihiko Nogami, Isabel Deisenhofer, Nicolas Derval, Laurence Jesel, Frederic Sacher, Sinikka Yli-mäyryAbstract:Background: Early repolarization is a common Electrocardiographic Finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest. Methods: We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of Electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects. Results: Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P
M J Whitehouse - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics and safety of cxa 101 a new antipseudomonal cephalosporin in healthy adult male and female subjects receiving single and multiple dose intravenous infusions
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Yigong Ge, M J Whitehouse, Ian R Friedland, George H TalbotAbstract:CXA-101 is a novel, broad-spectrum cephalosporin with excellent antipseudomonal activity. A Phase 1 study was performed to determine the safety, tolerability, and pharmacokinetics of CXA-101 after single- and multiple-dose intravenous administration over 1 h to healthy male and female subjects. In part 1 of the study, five cohorts of eight subjects each (six receiving CXA-101 and two receiving a placebo) received single ascending doses of 250, 500, 1,000, 1,500, and 2,000 mg. In part 2, cohorts 1 and 2 received 500 mg and 1,000 mg, respectively, every 8 h, and cohort 3 received 1,500 mg every 12 h; each cohort received dosing for 10 days. Standard safety and tolerability assessments were performed. Blood and urine pharmacokinetic samples were assayed by a validated bioanalytical method and analyzed using standard noncompartmental methodology. All 64 subjects completed dosing; none withdrew from the study. Drug-related systemic adverse events were infrequent and mild. Mild, non-treatment-limiting infusion site events occurred during multiple-dose administration. No clinically significant laboratory or Electrocardiographic Finding or dose-limiting toxicity was observed. CXA-101 exhibited dose-linear pharmacokinetics; the mean plasma half-life was ∼2.3 h. More than 90% of the administered dose was eliminated unchanged through renal excretion. In summary, CXA-101 administered as a 1-hour infusion was generally safe and well tolerated in single doses up to 2,000 mg and in multiple doses up to 3 g daily over 10 days. The favorable safety and predictable pharmacokinetic profile of CXA-101 support its continuing clinical development for the treatment of serious bacterial infections.
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pharmacokinetics and safety of cxa 101 a new antipseudomonal cephalosporin in healthy adult male and female subjects receiving single and multiple dose intravenous infusions
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: M J Whitehouse, Ian R Friedland, George H TalbotAbstract:CXA-101 is a novel, broad-spectrum cephalosporin with excellent antipseudomonal activity. A Phase 1 study was performed to determine the safety, tolerability, and pharmacokinetics of CXA-101 after single- and multiple-dose intravenous administration over 1 h to healthy male and female subjects. In part 1 of the study, five cohorts of eight subjects each (six receiving CXA-101 and two receiving a placebo) received single ascending doses of 250, 500, 1,000, 1,500, and 2,000 mg. In part 2, cohorts 1 and 2 received 500 mg and 1,000 mg, respectively, every 8 h, and cohort 3 received 1,500 mg every 12 h; each cohort received dosing for 10 days. Standard safety and tolerability assessments were performed. Blood and urine pharmacokinetic samples were assayed by a validated bioanalytical method and analyzed using standard noncompartmental methodology. All 64 subjects completed dosing; none withdrew from the study. Drug-related systemic adverse events were infrequent and mild. Mild, non-treatment-limiting infusion site events occurred during multiple-dose administration. No clinically significant laboratory or Electrocardiographic Finding or dose-limiting toxicity was observed. CXA-101 exhibited dose-linear pharmacokinetics; the mean plasma half-life was approximately 2.3 h. More than 90% of the administered dose was eliminated unchanged through renal excretion. In summary, CXA-101 administered as a 1-hour infusion was generally safe and well tolerated in single doses up to 2,000 mg and in multiple doses up to 3 g daily over 10 days. The favorable safety and predictable pharmacokinetic profile of CXA-101 support its continuing clinical development for the treatment of serious bacterial infections.