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Biomedical subjects

Arthur J Moss

Publications and source records attributed to Arthur J Moss.

At least 37 records · Page 2Linked to original sources
PubMed2006

High lipoprotein-associated phospholipase A2 is a risk factor for recurrent coronary events in postinfarction patients.

BACKGROUND: Recent studies demonstrate that lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor for cardiovascular disease presumably deriving from generation of proinflammatory and proatherogenic species through its hydrolytic activity on lipoprotein-associated phospholipids. The goal of this study was to assess the relationship of Lp-PLA2 with a set of thrombogenic, lipid, inflammatory, and metabolic blood markers and to determine whether plasma Lp-PLA2 is a risk factor for recurrent coronary events in postinfarction patients. METHODS: Factor analysis on the set of blood markers and Lp-PLA2 was performed for 766 patients of the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) postinfarction study. Recurrent coronary event risk was assessed as a function of blood marker concentrations and Lp-PLA2 by Cox proportional hazards multivariable regression adjusted for significant clinical covariates. RESULTS: Factor analysis revealed that Lp-PLA2 was associated with one factor dominated by cholesterol and apolipoprotein B and another factor dominated by HDL-cholesterol and triglycerides, with little association with an inflammatory factor dominated by C-reactive protein. Multivariable analysis demonstrated as significant and independent predictors of risk of secondary coronary events only apolipoprotein B in a model without Lp-PLA2 (hazard ratio, 1.66; 95% confidence interval, 1.14-2.40) and only Lp-PLA2 in a model with Lp-PLA2 included [1.90 (1.31-2.75)]. CONCLUSIONS: Lp-PLA2 is a significant and independent predictor of risk for recurrent coronary events in postinfarction patients, and Lp-PLA2 is related to both hypercholesterolemia and high triglyceride-low HDL dyslipidemia in this study population.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2006

The cost effectiveness of implantable cardioverter-defibrillators: results from the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

OBJECTIVES: We sought to evaluate the cost implications of the implantable cardioverter-defibrillator (ICD), using utilization, cost, and survival data from the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. BACKGROUND: This trial showed that prophylactic implantation of a defibrillator reduces the rate of mortality in patients who experienced a previous myocardial infarction and low left ventricular ejection fraction. Given the size of the eligible population, the cost effectiveness of the ICD has substantial implications. METHODS: Our research comprises the cost-effectiveness component of the randomized controlled trial, MADIT-II, based on utilization, cost, and survival information from 1,095 U.S. patients who were assigned randomly to receive an ICD or conventional medical care. Utilization data were converted to costs using a variety of national and hospital-specific data. The incremental cost-effectiveness ratio (iCER) was calculated as the difference in discounted costs divided by the difference in discounted life expectancy within 3.5 years. Secondary analyses included projections of survival (using three alternative assumptions), corresponding cost assumptions, and the resulting cost-effectiveness ratios until 12 years after randomization. RESULTS: During the 3.5-year period of the study, the average survival gain for the defibrillator arm was 0.167 years (2 months), the additional costs were 39,200 dollars, and the iCER was 235,000 dollars per year-of-life saved. In three alternative projections to 12 years, this ratio ranged from 78,600 dollars to 114,000 dollars. CONCLUSIONS: The estimated cost per life-year saved by the ICD in the MADIT-II study is relatively high at 3.5 years but is projected to be substantially lower over the course of longer time horizons.

Cost-Benefit Analysis↗
PubMed2006

Time dependence of defibrillator benefit after coronary revascularization in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

OBJECTIVES: The study was designed to assess the effect of elapsed time from coronary revascularization (CR) on the benefit of the implantable cardioverter-defibrillator (ICD) and the risk of sudden cardiac death (SCD) in patients with ischemic left ventricular dysfunction. BACKGROUND: The ICD improves survival in appropriately selected high-risk cardiac patients by 30% to 54%. However, in the Coronary Artery Bypass Graft (CABG)-Patch trial no evidence of improved survival was shown among a similar population of patients in whom an ICD was implanted prophylactically at the time of elective CABG. METHODS: The outcome by time from CR was analyzed in 951 patients in whom a revascularization procedure was performed before enrollment in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. RESULTS: The adjusted hazard ratio (HR) of ICD versus conventional therapy was 0.64 (p = 0.01) among patients enrolled more than six months after CR, whereas no survival benefit with ICD therapy was shown among patients enrolled six months or earlier after CR (HR = 1.19; p = 0.76). In the conventional therapy group, the risk of cardiac death increased significantly with increasing time from CR (p for trend = 0.009), corresponding mainly to a six-fold increase in the risk of SCD among patients enrolled more than six months after CR. CONCLUSIONS: In patients with ischemic left ventricular dysfunction, the efficacy of ICD therapy after CR is time dependent, with a significant life-saving benefit in patients receiving device implantation more than six months after CR. The lack of ICD benefit when implanted early after CR may be related to a relatively low risk of SCD during this time period.

Aged↗
PubMed2006

Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention.

Classifications of heart muscle diseases have proved to be exceedingly complex and in many respects contradictory. Indeed, the precise language used to describe these diseases is profoundly important. A new contemporary and rigorous classification of cardiomyopathies (with definitions) is proposed here. This reference document affords an important framework and measure of clarity to this heterogeneous group of diseases. Of particular note, the present classification scheme recognizes the rapid evolution of molecular genetics in cardiology, as well as the introduction of several recently described diseases, and is unique in that it incorporates ion channelopathies as a primary cardiomyopathy.

American Heart Association↗
PubMed2006

Implantable cardioverter-defibrillator therapy and risk of congestive heart failure or death in MADIT II patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) contributes to increased risk of morbidity and mortality. Data regarding the effectiveness of implantable cardioverter-defibrillator (ICD) therapy in AF patients are limited. OBJECTIVES: The purpose of this study was to evaluate the effectiveness of ICD therapy in patients with AF enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and to identify their risk for the combined endpoint of hospitalization for congestive heart failure or death. METHODS: The MADIT II cohort served as the source for data on the clinical course, cardiac events, and effectiveness of ICD therapy in AF patients. RESULTS: AF was found as baseline rhythm at enrollment in 102 (8%) MADIT II patients. In comparison to 1,007 patients in sinus rhythm, AF patients were older, more frequently were males, had wider QRS complex, and had higher blood urea nitrogen and creatinine levels (P <.05 for all parameters). ICD therapy was effective in reducing 2-year mortality in AF patients from 39% in 41 conventionally treated patients to 22% in 61 ICD-treated patients (hazard ratio = 0.51, P = .079). However, the combined endpoint of hospitalization for heart failure or death at 2 years was 69% and 59%, respectively (NS). AF was predictive for the combined endpoint of heart failure hospitalization or death (hazard ratio = 1.68, P = .040). New-onset AF in patients with baseline sinus rhythm was associated with increased risk of mortality (hazard ratio = 2.70, P <.001). CONCLUSION: MADIT II patients with AF benefit from ICD therapy, which reduces their mortality. MADIT II patients with AF are at high risk for developing heart failure.

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PubMed2006

Reduction in ventricular tachyarrhythmias with statins in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

OBJECTIVES: We evaluated whether statins have anti-arrhythmic effects by exploring the association of statin use with appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia/ventricular fibrillation (VT/VF) in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. BACKGROUND: A few studies have suggested that lipid-lowering drugs may have anti-arrhythmic effects in patients with coronary artery disease. METHODS: Patients receiving an ICD (n = 654; U.S. centers only) in the MADIT-II study were categorized by the percentage of days each patient received statins during follow-up (90% to 100%, n = 386; 11% to 89%, n = 116; and 0% to 10%, n = 152). The Kaplan-Meier method with significance testing by the log-rank statistic and time-dependent proportional hazards regression analysis were used to evaluate the effect of statin use on the probability of ICD therapy for the combined end point VT/VF or cardiac death and for the end point VT/VF. RESULTS: The cumulative rate of ICD therapy for VT/VF or cardiac death, whichever occurred first, was significantly reduced in those with > or =90% statin usage compared to those with lower statin usage (p = 0.01). The time-dependent statin:no statin therapy hazard ratio was 0.65 (p < 0.01) for the end point of VT/VF or cardiac death and 0.72 (p = 0.046) for VT/VF after adjusting for relevant covariates. CONCLUSIONS: Statin use in patients with an ICD was associated with a reduction in the risk of cardiac death or VT/VF, whichever occurred first, and was associated with a reduction in VT/VF episodes. These findings suggest that statins have anti-arrhythmic properties.

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PubMed2006

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death--executive summary: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society.

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Anti-Arrhythmia Agents↗
PubMed2006

Dental treatment of patients with long QT syndrome.

BACKGROUND: Long QT syndrome (LQTS) is associated with life-threatening cardiac arrhythmias causing syncope and sudden cardiac death, frequently precipitated by physical or psychological stress. TYPES OF STUDIES REVIEWED: The authors did a literature review of data published in peer-reviewed medical and dental journals. They also extracted epidemiologic information, correlations between genetic mutations and disease onset and progression, and data regarding outcomes of therapy from published peer-reviewed studies and the cohort population belonging to the International Long QT Syndrome Registry. RESULTS: LQTS is diagnosed after an unexpected cardiac event or through QT interval prolongation on an electrocardiogram. Gene mutation identification in LQTS provides insight into respective proarrhythmogenic factors and indicated therapeutic regimens. beta-blockers are the initial treatment for two of the three major forms of LQTS. Patients refractory to beta-antiadrenergic therapy may benefit from one or more of the following: cardiac pacemakers, implanted cardioverter defibrillators and left cardiac sympathetic denervation. CONCLUSIONS: Clinical studies are needed to investigate the safety of treating patients in an ambulatory setting. CLINICAL IMPLICATIONS: Preventive measures are recommended, including evaluation by a cardiac specialist before any dental intervention, use of anxiolytic protocols, avoidance of drugs that prolong the QT interval, and provision of treatment in a setting in which medical emergencies can be managed expeditiously. Dental treatment in a hospital and use of a general anesthetic administered by anesthesiologists are recommended for procedures in which anxiety and adrenergic stimulation would not be suppressed sufficiently in an ambulatory environment.

Adrenergic beta-Antagonists↗
PubMed2005

Predictive value of ventricular arrhythmia inducibility for subsequent ventricular tachycardia or ventricular fibrillation in Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients.

UNLABELLED: In the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II, implantable cardioverter-defibrillator (ICD)-randomized patients underwent electrophysiologic testing. Both inducible and noninducible patients received an ICD. We correlated inducibility with the occurrence of subsequent ventricular tachycardia (VT) or ventricular fibrillation (VF). Intracardiac ICD electrograms for subsequent events were analyzed to categorize the spontaneous arrhythmia as VT or VF. The two-year Kaplan-Meier event rate for VT in inducible patients was 29.0% versus 19.3% in noninducible patients. However, ICD therapy for spontaneous VF was less common at two years in inducible patients (3.2%) than in noninducible patients (8.6%). In the MADIT II study, inducibility predicted an increased likelihood of VT but decreased VF. OBJECTIVES: We correlated electrophysiologic inducibility with spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II. BACKGROUND: In the MADIT II study, 593 (82%) of 720 implantable cardioverter-defibrillator (ICD) randomized patients underwent electrophysiologic testing. Patients received an ICD whether they were inducible or not. METHODS: A "standard" inducibility definition included sustained monomorphic or polymorphic VT induced with three or fewer extrastimuli or VF induced with two or fewer extrastimuli. We compared a narrow inducibility definition (only monomorphic VT) and a broad definition (standard definition plus VF with three extrastimuli). We used ICD-stored electrograms to categorize spontaneous VT or VF. RESULTS: Inducible patients (standard definition) had a greater likelihood of experiencing ICD therapy for VT than noninducible patients (p = 0.023). Unexpectedly, ICD therapy for spontaneous VF was less common (p = 0.021) in inducible patients than in noninducible patients. The two-year Kaplan-Meier event rate for VT or VF was 29.4% for inducible patients and 25.5% for noninducible patients. Standard inducibility did not predict the combined end point of VT or VF (p = 0.280, by log-rank analysis). The narrow inducibility definition outperformed the standard definition, whereas the broad definition appeared inferior to the standard definition. CONCLUSIONS: In the MADIT II study patients, inducibility was associated with an increased likelihood of VT. Noninducible MADIT II study subjects using this electrophysiologic protocol had a considerable VT event rate and a higher VF event rate than inducible patients. Induction of polymorphic VT or VF, even with double extrastimuli, appears less relevant than induction of monomorphic VT.

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PubMed2005

Elevated HDL is a risk factor for recurrent coronary events in a subgroup of non-diabetic postinfarction patients with hypercholesterolemia and inflammation.

Recent studies demonstrate important roles for inflammation in development of atherosclerosis with current attention focusing on interactions of inflammation with traditional lipoprotein risk factors. Since the nature of such relationships is largely unknown, we sought to investigate interactions of inflammation with hyperlipidemia in generating cardiovascular risk in a way that would allow recognition of such interactions whether anticipated or not. Thus, we searched for subgroups at high risk for recurrent coronary events in 767 non-diabetic postinfarction patients using an exploratory three-dimensional graphical screening technique with previously established factor analysis-derived inflammatory and lipoprotein-related factors. Results indicated a high-risk patient subgroup defined by factor interaction that was best characterized clinically by high levels of C-reactive protein (CRP) and total cholesterol. Kaplan-Meier and Cox multivariate analysis confirmed high-risk. Additionally, within-subgroup risk related to metabolic, inflammatory, and thrombogenic blood markers was assessed using Cox analysis with results showing only elevated HDL as a significant and independent predictor of risk with hazard ratio, 2.24 (95% CI; 1.12, 4.49; p = 0.023). We conclude that in non-diabetic postinfarction patients, elevated HDL is predictive of risk of recurrent coronary events within a subgroup of patients characterized by simultaneous elevations in serum CRP and total cholesterol.

C-Reactive Protein↗
PubMed2005

Factors influencing appropriate firing of the implanted defibrillator for ventricular tachycardia/fibrillation: findings from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II).

OBJECTIVES: The purpose of this study was to prospectively examine the role of clinical, laboratory, echocardiographic, and electrophysiological variables as predictors of appropriate initial implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) or death in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) population. BACKGROUND: There is limited information regarding the determinants of appropriate ICD therapy in patients with reduced ventricular function after a myocardial infarction. METHODS: We used secondary analysis in one arm of a multicenter randomized clinical trial in patients with a previous myocardial infarction and reduced left ventricular function. RESULTS: We analyzed baseline and follow-up data on 719 patients enrolled in the ICD arm of the MADIT-II study. Appropriate ICD therapy was observed in 169 subjects. Clinical, laboratory, echocardiographic, and electrophysiological variables, along with measures of clinical instability such as interim hospitalization for congestive heart failure (IH-CHF) and interim hospitalization for coronary events (IH-CE), were examined with proportional hazards models and Kaplan-Meier time-to-event curves before and after first interim hospitalization. Interim hospitalization-CHF, IH-CE, no beta-blockers, digitalis use, blood urea nitrogen (BUN) >25, body mass index (BMI) > or =30 kg/m2, and New York Heart Association functional class >II were associated with increased risk for appropriate ICD therapy for VT, VF, or death. In a multivariate (stepwise selection) analysis, IH-CHF was associated with an increased risk for the end point of either VT or VF (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.69 to 3.74, p < 0.001) and for the combined end point of VT, VF, or death (HR 2.97, 95% CI 2.15 to 4.09, p < 0.001). Interim hospitalization-CE was associated with an increased risk for VT, VF, or death (HR 1.66, 95% CI 1.09 to 2.52, p = 0.02). CONCLUSIONS: These results provide important mechanistic information, suggesting that worsening clinical condition and cardiac instability, as reflected by an IH-CHF or IH-CE, are subsequently associated with a significant increase in the risk for appropriate ICD therapy (for VT/VF) and death.

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PubMed2005

Effects of beta-blockers on implantable cardioverter defibrillator therapy and survival in the patients with ischemic cardiomyopathy (from the Multicenter Automatic Defibrillator Implantation Trial-II).

This study examined the effects of beta blockers on (1) appropriate implantable cardioverter defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF), (2) inappropriate ICD therapy for atrial fibrillation or supraventricular tachycardia, and (3) survival in 691 patients who received ICDs in the Multicenter Automatic Defibrillator Implantation Trial-II. The study population involved 258 patients who were not receiving beta blockers and 433 who were receiving metoprolol (n = 192), atenolol (n = 58), or carvedilol (n = 182). Patients receiving beta blockers were divided into the upper quartile and lower 3 quartiles of the drug doses they were taking. Patients receiving the higher doses of beta blockers (those in the top quartile of doses) had a significant reduction in the risk for VT or VF requiring ICD therapy compared with patients not receiving beta blockers (hazard ratio 0.48, p = 0.02). The frequency of inappropriate ICD therapy for supraventricular tachyarrhythmias was not significantly different among the 3 treatment groups (p = 0.32). Beta-blocker use at the 2 dosage levels was associated with significant improvement in survival compared with the nonuse of beta blockers (hazard ratios 0.42 to 0.44, p <0.01). In conclusion, beta blockers reduce the risk for VT or VF and improve survival in ICD-treated patients with ischemic cardiomyopathy.

Adrenergic beta-Antagonists↗