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Biomedical subjects

Arthur J Moss

Publications and source records attributed to Arthur J Moss.

At least 55 records · Page 3Linked to original sources
PubMed2005

Comparison of efficacy of implanted cardioverter-defibrillator in patients with versus without diabetes mellitus.

In the second Multicenter Automatic Defibrillator Implantation Trial, patients with a previous myocardial infarction and left ventricular ejection fraction < or =0.30 benefited significantly from prophylactic implantable cardioverter-defibrillator (ICD) placement. Diabetic patients who had a myocardial infarction had a worse prognosis compared with nondiabetics. The present study used data from the second Multicenter Automatic Defibrillator Implantation Trial to assess the efficacy of ICD placement on survival in diabetic patients. Of the 1,232 patients in the second Multicenter Automatic Defibrillator Implantation Trial, 489 were characterized as diabetic. They were more likely to be New York Heart Association class II to IV, be hypertensive, have renal dysfunction, have an increased body mass index, and to take diuretic drugs. Diabetic patients had a 24% greater adjusted risk of death than nondiabetic patients. The hazard ratio (HR) for the risk of death in patients treated with the ICD compared with conventional therapy was similar in diabetics (HR 0.61; 95% confidence interval [CI] 0.38 to 0.98) and nondiabetics (HR 0.71; 95% CI 0.49 to 1.05), with no evidence of interaction. Thus, diabetic patients derive a similar benefit from ICD therapy despite being sicker and having a higher mortality rate overall.

Aged↗
PubMed2005

Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction.

The association of a group of prespecified atherosclerotic risk genotypes with recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) was investigated in a cohort of 1,008 patients after infarction during an average follow-up of 28 months. We used a carrier-ship approach with time-dependent survivorship analysis to evaluate the average risk of each carried genotype. Contrary to expectation, the hazard ratio for recurrent coronary events per carried versus noncarried genotype was 0.89 (95% confidence interval 0.80 to 0.99, p = 0.03) after adjustment for relevant genetic, clinical, and environmental covariates. This hazard ratio, derived from the 7 prespecified genotypes, indicated an average 11% reduction in the risk of recurrent coronary events per carried versus noncarried genotype. At 1 year after hospital discharge, the cumulative probability of recurrent coronary events was 26% in those who carried < or =1, 20% for those with 2 to 4, and 13% for those with > or =5 of these genotypes (p = 0.02). This unexpected risk reversal is a likely consequence of changes in the mix of risk factors in pre- and postinfarction populations. In conclusion, this under appreciated, population-based, risk-reversal phenomenon may explain the inconsistent associations of genetic risk factors with outcome events in previous reports involving coronary populations with different risk attributes.

Aged↗
PubMed2005

Implantable cardioverter-defibrillator efficacy in patients with heart failure and left ventricular dysfunction (from the MADIT II population).

The Multicenter Automatic Defibrillator Implantation Trial II demonstrated a significant 31% reduction in the risk of mortality in postinfarction patients with low ejection fraction (EF < or =30%). Recently, results from the Sudden Death in Heart Failure Trial indicated that a subgroup of patients with New York Heart Association (NYHA) class III heart failure had less benefit from an implantable cardioverter-defibrillator (ICD) than patients with less advanced heart failure. This study evaluates the association between NYHA class, EF, and blood urea nitrogen (BUN) levels as measures of heart failure and left ventricular dysfunction, and ICD benefit in reducing mortality as well as the association of these parameters with ICD therapy for ventricular tachyarrhythmias. NYHA class I was identified in 442 patients (36%), class II in 425 (35%), and class III in 350 patients (29%). EF < or =20% was present in 472 patients (38%), EF of 21% to 25% in 359 patients (29%), and EF of 26% to 30% in 401 patients (33%). BUN < or =25 mg/dl was present in 850 patients (70%) and >25 mg/dl in 368 patients (30%). Patients with higher NYHA class and BUN had higher mortality (34%) and a higher risk of arrhythmic events (33% to 35%) than patients in lower functional groups (16% to 20%). EF did not differentiate the risk. There was no evidence for significant interactions between mortality, ICD therapy, and tested parameters. In conclusion, patients with more advanced heart failure have a higher risk of mortality and arrhythmic events than patients with less severe disease. However, there is no significant difference in the benefit from ICD therapy among the above subgroups of patients in the Multicenter Automatic Defibrillator Implantation Trial.

Aged↗
PubMed2005

Serum glucose and triglyceride determine high-risk subgroups in non-diabetic postinfarction patients.

A strategy was developed to identify subgroups at high risk for recurrent coronary events in non-diabetic postinfarction patients as a function of metabolic, inflammatory, and thrombogenic blood markers. A graphical screening technique for presumptively identifying high-risk subgroups from outcome prevalence maps was devised that was equally sensitive for all values of risk factors in contrast to traditional approaches where risk is presumed for the highest or the lowest values. Traditional statistical analysis confirms high risk in identified subgroups. Serum glucose and triglyceride served as bivariate search domain. Results demonstrated three high-risk subgroups. One was characterized as pre-diabetic; another as metabolic syndrome-enriched; and the third, with unexpectedly high risk, as normoglycemic and modestly hypertriglyceridemic. Within-subgroup risk as determined by Cox proportional hazards model gave for odds ratios and 95 percentile confidence intervals: glucose, 2.49 (1.17-5.33) in pre-diabetic; PAI-1, 3.95 (1.81-8.61) in metabolic syndrome-enriched; and BMI, 2.79 (1.17-6.63) and fibrinogen, 2.79 (1.29-6.04) in normoglycemic, modestly hypertriglyceridemic patients. We conclude that the graphical approach holds promise in screening for high-risk patient subgroups. Finding different within-subgroup predictors of risk underscores the notion of context-dependent risk, an observation that may be relevant for determining optimal use of emerging risk factors.

Biomarkers↗
PubMed2005

Sudden cardiac death without structural heart disease: update on the long QT and Brugada syndromes.

The long QT syndrome (LQTS) and the Brugada syndrome (BrS) are the most common genetic causes of malignant ventricular arrhythmias and sudden cardiac death in young patients with normal cardiac morphology. To date, more than 250 different mutations in seven genes have been identified as causing LQTS, whereas the only gene identified to be linked to BrS is SCN5A. In both syndromes, gene-specific mutations have been shown to be associated with specific phenotypic expressions. Risk stratification in LQTS and BrS is based mainly upon a constellation of electrocardiographic findings and a history of prior symptoms. In patients identified as high risk for arrhythmic mortality, the implantable cardioverter defibrillator is the most effective treatment and has been shown to provide near-complete protection during long-term follow-up.

Bundle-Branch Block↗
PubMed2005

ECGScan: a method for conversion of paper electrocardiographic printouts to digital electrocardiographic files.

BACKGROUND: Measurements of parameters from electrocardiograms (ECGs) are still largely performed from paper ECG records. Recent guidelines from regulatory agencies and, in particular, the requirement of the Food and Drug Administration to enforce the digital submission of annotated ECGs have triggered significant efforts in the pharmaceutical industry, which, to comply with the new guidelines, is adopting digital ECG technology. At the same time, the new requirements justify the need for tools to convert existing paper ECG records into digital format, particularly for retrospective studies. METHODS: This article presents ECGScan, a computer application developed for the conversion of paper ECG records to digital ECG files. An image processing engine is used to first detect the underlying grid and, subsequently, to extrapolate the ECG waveforms using a technique based on active contour modeling. RESULTS: ECGScan was validated using a set of 60 ECGs for which both the original digital waveform and paper printouts were available. Sample-by-sample comparisons provided evidence of a robust wave reconstruction (root mean square value from 169 PQRST complexes was 16.8+/-11.8 microV). Semiautomatic measurements of QT intervals performed on 144 complexes also indicated a strong agreement between original and derived ECGs (DeltaQT=0.577+/-5.41 milliseconds). CONCLUSIONS: ECGScan provides a robust reconstruction of a digital ECG, both in waveform reconstruction and in QT measurements performed on original (digital) ECGs and on digitized ECGs from paper printouts.

Artificial Intelligence↗
PubMed2005

The clinical implications of cumulative right ventricular pacing in the multicenter automatic defibrillator trial II.

INTRODUCTION: This study was designed to assess whether right ventricular pacing in the implantable cardioverter defibrillator (ICD) arm of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II was associated with an unfavorable outcome. METHODS AND RESULTS: Data on the number of ventricular paced beats were available in 567 (76%) of 742 MADIT II patients with ICDs. The number of ventricular paced beats over the total number of beats showed a bimodal distribution with patients being predominantly paced or nonpaced. Therefore, patients were dichotomized at 0-50% and 51-100% of cumulative pacing with median pacing rate 0.2% and 95.6%, respectively. Endpoints included new or worsening heart failure, appropriate ICD therapy for VT/VF, and the combined endpoint of heart failure or death. Clinical features associated with frequent ventricular pacing included age >or=65 years, advanced NYHA heart failure class, LVEF < 0.25, first degree AV and bundle branch block, and amiodarone use. During follow-up, 119 patients (21%) had new or worsened heart failure, 130 (23%) had new or worsened heart failure or death, and 142 (25%) had appropriate therapy for VT/VF. In comparison to patients with infrequent pacing, those with frequent pacing had significantly higher risk of new or worsened heart failure (hazard ratio = 1.93; P = 0.002) and VT/VF requiring ICD therapy (HR = 1.50; P = 0.02). CONCLUSIONS: Patients in MADIT II who were predominantly paced had a higher rate of new or worsened heart failure and were more likely to receive therapy for VT/VF. These results suggest the deleterious consequences of RV pacing, particularly in the setting of severe LV dysfunction.

Aged↗
PubMed2005

Clinical course and implantable cardioverter defibrillator therapy in postinfarction women with severe left ventricular dysfunction.

BACKGROUND: There are limited data regarding implantable cardioverter defibrillator (ICD) therapy in postinfarction women with severe left ventricular dysfunction. The aim of this study was to evaluate the risk of cardiac events and effects of ICD therapy in women as compared to men enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II). METHODS AND RESULTS: Among 1,232 patients enrolled in MADIT II, there were 192 (16%) women and 1,040 (84%) men. When compared to men, women had an increased frequency of NYHA class > or =II (70 vs 63%; P = 0.067), hypertension (60% vs 52%; P = 0.047), diabetes (42% vs 34%; P = 0.027), and LBBB (25% vs 17%; P = 0.011), and less frequent CABG surgery (42% vs 60%; P < 0.001). The 2-year cumulative mortality in patients randomized to conventional therapy was not significantly different in women and men (30% and 20%, respectively; P = 0.19). Adjusting for relevant clinical covariates, the hazard ratios for ICD effectiveness were similar in women (0.57; 95% CI = 0.28-1.18; P = 0.132) and men (0.66; 95% CI = 0.48-0.91; P = 0.011). The risk of appropriate ICD therapy for VT/VF was lower in women than in men (hazard ratio = 0.60 for female vs male gender; 95% CI = 0.37-0.98; P = 0.039). CONCLUSIONS: MADIT II women had similar mortality and similar ICD effectiveness when compared to men. MADIT II women with ICDs had a lower risk of arrhythmic events with fewer episodes of ventricular tachycardia than men.

Aged↗
PubMed2005

Differences in outcomes between patients treated with single- versus dual-chamber implantable cardioverter defibrillators: a substudy of the Multicenter Automatic Defibrillator Implantation Trial II.

OBJECTIVES: We sought to evaluate the influence of single- versus dual-chamber implantable cardioverter defibrillators (ICDs) on the occurrence of heart failure and mortality as well as appropriate and inappropriate ICD therapy in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II). BACKGROUND: In MADIT-II, ICD therapy in patients with a prior myocardial infarction and ejection fraction < or =0.30 was associated with a 31% reduction in risk of mortality when compared to conventionally treated patients. An unexpected finding was an increased occurrence of hospitalization for heart failure in the ICD group. METHODS: Data from 717 patients randomized to ICD therapy with single- or dual-chamber pacing devices in MADIT-II were retrospectively analyzed. Endpoints selected for analysis included death from any cause, new or worsening heart failure requiring hospitalization, death or heart failure, appropriate therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF), and inappropriate ICD therapy for atrial fibrillation or supraventricular tachycardia. RESULTS: A total of 404 single-chamber ICDs (S-ICDs) and 313 dual-chamber ICDs (D-ICDs) were implanted. Patients receiving D-ICDs were at a higher risk at baseline than those receiving S-ICDs, with older age, higher NYHA class, more frequent prior CABG, wider QRS complex, more LBBB, higher BUN level, a history of more atrial arrhythmias requiring treatment, and a longer time interval from their index myocardial infarction to enrollment. While there was a trend toward an increase in adverse outcomes in the D-ICD group, no statistically significant differences in heart failure or mortality were observed between S-ICD versus D-ICD groups. CONCLUSIONS: Patients with D-ICDs had a nonsignificant trend toward higher mortality and heart failure rates than patients with S-ICDs.

Arrhythmias, Cardiac↗
PubMed2005

Cost-effectiveness of implanted defibrillators in young people with inherited cardiac arrhythmias.

BACKGROUND: The implanted cardioverter-defibrillator (ICD) has been shown to improve survival in adult patients with high risk acquired cardiac disease, with a cost-effectiveness ratio in the range of $30,000 to $185,000 per quality-adjusted-life-year saved. However, data on the benefit and cost-effectiveness of device therapy in high-risk patients with inherited cardiac disorders are limited. METHODS: We developed two separate computer-based analytical models to compare non-ICD with ICD therapy in patients (age range: 10-75 years) with long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM). In each disease entity patients were stratified into low-risk (no known risk factors); high-risk (known risk factors [primary prevention]); and very high-risk (prior near-fatal events [secondary prevention]). Net costs were defined as the difference between costs resulting from treatment of the disease and savings due to gained productivity attributable to prevention of sudden cardiac death. Outcome was defined as costs per quality-adjusted life-years saved. RESULTS: In LQTS, defibrillator therapy was shown to be cost effective in high-risk male patients (incremental cost-effectiveness ratio [ICER]=$3328 per quality-adjusted-life-year saved), and cost saving in high-risk females (ICER=$7102 gained per quality-adjusted-life-year saved) and very high-risk males and females (ICER=$15,483 and 19,393 gained per quality-adjusted-life-year saved, respectively). In HCM, defibrillator therapy was cost saving in both male and female high-risk (ICER=$17,892 and $17,526 gained per quality-adjusted-life-year saved, respectively) and very high-risk (ICER $22,944 and $22,329 gained per quality-adjusted-life-year saved, respectively) patients. Defibrillator therapy was not shown to be cost effective in low-risk patients with either LQTS or HCM (ICER in the range of $400,000 to $600,000 lost per quality-adjusted-life-year saved). Sensitivity analyses were consistent with the results in each risk group. CONCLUSIONS: In appropriately selected patients with inherited cardiac disorders, early intervention with ICD therapy is cost-effective to cost saving due to added years of gained productivity when the lifespan of an individual at risk is considered.

Arrhythmias, Cardiac↗
PubMed2005

Safety and efficacy of flecainide in subjects with Long QT-3 syndrome (DeltaKPQ mutation): a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: We conducted a study of chronic therapy with flecainide versus placebo in a small group of LQT-3 patients with the DeltaKPQ deletion to evaluate the safety and efficacy of flecainide in this genetic disorder. In vitro studies have shown that flecainide provides correction of the impaired inactivation associated with the DeltaKPQ deletion. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted with flecainide and placebo in six male LQT-3 subjects with the DeltaKPQ deletion. RESULTS: The lowest possible dose of flecainide associated with at least a 40 ms reduction in the QTc interval was determined in an initial open-label, dose-ranging investigation using one-fourth or half of the recommended maximal antiarrhythmic flecainide dose. QTc reduction was achieved with a flecainide dose of 1.5 mg/kg per day in 4 subjects and with 3.0 mg/kg per day in 2 subjects. Subjects were randomized to four 6-month alternating periods of flecainide and placebo therapy based on the open-label dose findings. Average QTc values during placebo and flecainide therapies were 534 ms and 503 ms, respectively, with an adjusted reduction in QTc of -27.1 ms (95% confidence interval: -36.8 ms to -17.4 ms; P<0.001) at a mean flecainide blood level of 0.11+/-0.05 microg/ml. Minimal prolongation in QRS occurred (mean: +2.5 ms), and there were no major adverse cardiac effects. CONCLUSIONS: Chronic low-dose flecainide significantly shortens the QTc interval in LQT-3 subjects with the DeltaKPQ mutation. No major adverse drug effects were observed with flecainide during this trial, but the sample size is not large enough to evaluate the safety of flecainide therapy in patients with this mutation.

Adolescent↗
PubMed2005

Assessment of the stability of the individual-based correction of QT interval for heart rate.

BACKGROUND: Modeling the relationship between QT intervals and previous R-R values remains a challenge of modern quantitative electrocardiography. The technique based on an individual regression model computed from a set of QT-R-R measurements is presented as a promising alternative. However, a large set of QT-R-R measurements is not always available in clinical trials and there is no study that has investigated the minimum number of QT-R-R measurements needed to obtain a reliable individual QT-R-R model. In this study, we propose guidelines to ensure appropriate use of the regression technique for heart rate correction of QT intervals. METHOD: Holter recordings from 205 healthy subjects were included in the study. QT-R-R relationships were modeled using both linear and parabolic regression techniques. Using a bootstrapping technique, we computed the stability of the individual correction models as a function of the number of measurements, the range of heart rate, and the variance of R-R values. RESULTS: The results show that the stability of QT-R-R individual models was dependent on three factors: the number of measurements included in its design, the heart-rate range used to design the model, and the T-wave amplitude. Practically our results showed that a set of 400 QT-R-R measurements with R-R values ranging from 600 to 1000 ms ensure a stable and reliable individual correction model if the amplitude of the T wave is at least 0.3 mV. Reducing the range of heart rate or the number of measurements may significantly impact the correction model. CONCLUSION: We demonstrated that a large number of QT-R-R measurements (approximately 400) is required to ensure reliable individual correction of QT intervals for heart rate.

Adult↗