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Biomedical subjects

Paul S Chan

Publications and source records attributed to Paul S Chan.

9 recordsLinked to original sources
PubMed2006

Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who benefit from implantable cardioverter-defibrillator therapy.

OBJECTIVES: This study sought to assess whether implantable cardioverter-defibrillators (ICDs) have different mortality benefits among patients with ischemic cardiomyopathy who screen negative and non-negative (positive and indeterminate) for microvolt T-wave alternans (MTWA). BACKGROUND: Microvolt T-wave alternans has been proposed as an effective tool for risk stratification. However, no studies have examined whether ICD benefits differ by MTWA group. METHODS: We developed a prospective cohort of 768 patients with ischemic cardiomyopathy (left ventricular ejection fraction < or =35%) and no prior sustained ventricular arrhythmia, of which 392 (51%) received ICDs. The mean follow-up time was 27 +/- 12 months. Propensity scores for ICD implantation based on the variables most likely to influence defibrillator implantation were developed for each MTWA cohort. Multivariable Cox analyses that controlled for propensity score, demographics, and clinical variables evaluated the degree to which ICDs decreased mortality risk for each MTWA group. RESULTS: We identified 514 (67%) patients with a non-negative MTWA test result. After multivariable adjustment, ICDs were associated with lower all-cause mortality in MTWA-non-negative patients (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.27 to 0.76, p = 0.003) but not in MTWA-negative patients (HR 0.85, 95% CI 0.33 to 2.20, p = 0.73) (for interaction, p = 0.04), with the mortality benefit in MTWA-non-negative patients largely mediated through arrhythmic mortality reduction (HR 0.30, 95% CI 0.13 to 0.68, p = 0.004). The number needed to treat with an ICD for 2 years to save 1 life was 9 among MTWA-non-negative patients and 76 among MTWA-negative patients. CONCLUSIONS: In patients with ischemic cardiomyopathy and no prior history of ventricular arrhythmia, mortality reduction with ICD implantation differs by MTWA status, with implications for risk stratification and health policy.

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PubMed2006

Effectiveness of implantable cardioverter-defibrillators in patients with ischemic heart disease and left ventricular dysfunction.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) have been shown in primary prevention efficacy trials to reduce mortality in patients with ischemic heart disease and left ventricular dysfunction. To investigate the generalizabilty of this mortality reduction, we examined the effectiveness of ICDs in clinical practice. METHODS: We developed a prospective multicenter cohort of 770 patients with ischemic left ventricular dysfunction (ejection fraction < or =35%) and without a history of ventricular arrhythmia, of whom 395 (52%) received ICDs. Mean +/- SD follow-up was 27 +/- 12 months. We assessed the degree to which ICDs decreased mortality risk using Cox proportional hazards analyses that controlled for clinical predictors of death, receipt of ICD (a propensity score analysis), and predictors of arrhythmic death (including electrophysiologic variables). RESULTS: Multivariate Cox analyses showed that those with ICDs had significantly lower all-cause mortality (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.33-0.86). This mortality reduction was mediated through dramatically lower arrhythmia-related mortality (HR, 0.35; 95% CI, 0.17-0.73), with no significant effect on cardiovascular nonarrhythmic (HR, 0.81; 95% CI, 0.34-1.96) and noncardiovascular (HR, 0.76; 95% CI, 0.29-2.05) mortality. No differences were found between the ICD and non-ICD groups for a composite outcome of all-cause mortality, appropriate ICD shocks, or documented symptomatic ventricular arrhythmia, which suggests that the 2 groups had similar baseline risk for life-threatening arrhythmic events (HR, 0.96; 95% CI, 0.63-1.45). CONCLUSION: In clinical practice, ICDs appear to reduce all-cause and arrhythmic rates of mortality at levels similar to those found in primary prevention trials.

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PubMed2006

Cost-effectiveness of a microvolt T-wave alternans screening strategy for implantable cardioverter-defibrillator placement in the MADIT-II-eligible population.

OBJECTIVES: This study was designed to compare the cost-effectiveness of implantable cardioverter-defibrillator (ICD) placement with and without risk stratification with microvolt T-wave alternans (MTWA) testing in the MADIT-II (Second Multicenter Automatic Defibrillator Implantation Trial) eligible population. BACKGROUND: Implantable cardioverter-defibrillators have been shown to prevent mortality in the MADIT-II population. Microvolt T-wave alternans testing has been shown to be effective in risk stratifying MADIT-II-eligible patients. METHODS: On the basis of published data, cost-effectiveness of three therapeutic strategies in MADIT-II-eligible patients was assessed using a Markov model: 1) ICD placement in all; 2) ICD placement in patients testing MTWA non-negative;, and 3) medical management. Outcomes of expected cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness were determined for patient lifetime. RESULTS: Under base-case assumptions, providing ICDs only to those who test MTWA non-negative produced a gain of 1.14 QALYs at an incremental cost of 55,700 dollars when compared to medical therapy, resulting in an incremental cost-effectiveness ratio (ICER) of 48,700 dollars/QALY. When compared with a MTWA risk-stratification strategy, placing ICDs in all patients resulted in an ICER of 88,700 dollars/QALY. Most (83%) of the potential benefit was achieved by implanting ICDs in the 67% of patients who tested MTWA non-negative. Results were most sensitive to the effectiveness of MTWA as a risk-stratification tool, MTWA negative screen rate, cost and efficacy of ICD therapy, and patient risk for arrhythmic death. CONCLUSIONS: Risk stratification with MTWA testing in MADIT-II-eligible patients improves the cost-effectiveness of ICDs. Implanting defibrillators in all MADIT-II-eligible patients, however, is not cost-effective, with one-third of patients deriving little additional benefit at great expense.

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PubMed2006

Cost-effectiveness of radiofrequency catheter ablation for atrial fibrillation.

OBJECTIVES: We sought to compare the cost-effectiveness of left atrial catheter ablation (LACA), amiodarone, and rate control therapy in the management of atrial fibrillation (AF). BACKGROUND: Left atrial catheter ablation has been performed to eliminate AF, but its cost-effectiveness is unknown. METHODS: We developed a decision-analytic model to evaluate the cost-effectiveness of LACA in 55- and 65-year-old cohorts with AF at moderate and low stroke risk. Costs, health utilities, and transition probabilities were derived from published literature and Medicare data. We performed primary threshold analyses to determine the minimum level of LACA efficacy and stroke risk reduction needed to make LACA cost-effective at 50,000 dollars and 100,000 dollars per quality-adjusted life-year (QALY) thresholds. RESULTS: In 65-year-old subjects with AF at moderate stroke risk, relative reduction in stroke risk with an 80% LACA efficacy rate for sinus rhythm restoration would need to be > or =42% and > or =11% to yield incremental cost-effectiveness ratios (ICERs) <50,000 dollars and 100,000 dollars per QALY, respectively. Higher and lower LACA efficacy rates would require correspondingly lower and higher stroke risk reduction for equivalent ICER thresholds. In the 55-year-old moderate stroke risk cohort, lower LACA efficacy rates or stroke risk reduction would be needed for the same ICER thresholds. In patients at low stroke risk, LACA was unlikely to be cost-effective. CONCLUSIONS: The use of LACA may be cost-effective in patients with AF at moderate risk for stroke, but it is not cost-effective in low-risk patients. Our threshold analyses may provide a framework for the design of future clinical trials by providing effect size estimates for LACA efficacy needed.

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PubMed2006

Prognostic utility of microvolt T-wave alternans in risk stratification of patients with ischemic cardiomyopathy.

OBJECTIVES: The purpose of this study was to assess if microvolt T-wave alternans (MTWA) is an independent predictor of mortality in patients with ischemic cardiomyopathy. BACKGROUND: Microvolt T-wave alternans has been proposed as an effective tool for identifying high-risk patients with ischemic cardiomyopathy who are likely to benefit from implantable cardioverter-defibrillator (ICD) therapy. However, earlier studies have been limited in their ability to control for baseline differences between MTWA-negative and -non-negative (positive and indeterminate) patients. METHODS: We enrolled 768 consecutive patients with ischemic cardiomyopathy (left ventricular ejection fraction < or =35%) and no prior history of ventricular arrhythmia. All patients underwent baseline MTWA testing and were classified as MTWA negative or non-negative. Multivariable Cox regression analyses, stratified by ICD status, were used to determine the association between MTWA testing and mortality after adjusting for demographic, clinical, and treatment differences between MTWA-negative and -non-negative patients. RESULTS: We identified 514 (67%) patients with a non-negative MTWA test. After multivariable adjustment, a non-negative MTWA test was associated with a significantly higher risk for all-cause (stratified hazard ratio [HR] = 2.24 [95% confidence interval 1.34 to 3.75]; p = 0.002) and arrhythmic mortality (stratified HR = 2.29 [1.00 to 5.24]; p = 0.049) but not for nonarrhythmic mortality (stratified HR = 1.77 [0.84 to 3.74]; p = 0.13). In subgroup analyses, a non-negative MTWA test was also associated with a higher risk for all-cause mortality in patients with ejection fractions < or =30% (stratified HR = 2.10 [1.18 to 3.73]; p = 0.01) and after excluding those with indeterminate MTWA tests (stratified HR = 2.08 [1.18 to 3.66]; p = 0.01). CONCLUSIONS: Microvolt T-wave alternans is a strong and independent predictor of all-cause and arrhythmic mortality in patients with ischemic cardiomyopathy.

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PubMed2005

Mortality reduction by implantable cardioverter-defibrillators in high-risk patients with heart failure, ischemic heart disease, and new-onset ventricular arrhythmia: an effectiveness study.

OBJECTIVES: To investigate the generalizability of the reduction in mortality posed by implantable cardioverter-defibrillators, we examined the effectiveness of defibrillators as applied in routine medical practice. BACKGROUND: Implantable cardioverter-defibrillators have been shown to be efficacious in the primary and secondary prevention of overall and cardiovascular mortality in clinical trials. METHODS: Using the National Veterans Administration database, we identified a cohort of 6,996 patients from 1995 to 1999 with new-onset ventricular arrhythmia and pre-existing ischemic heart disease and congestive heart failure, of which 1,442 received a defibrillator, and followed them for three years to determine rates of mortality. With multivariate logistic regression analyses that adjusted for demographics, illness severity, and comorbidity, we assessed overall, cardiovascular, and noncardiovascular rates of mortality. To further address potential confounding, we also stratified the cohort by quintiles using a multivariable propensity score for each patient and determined mortality rates. RESULTS: For the overall cohort, multivariate regression showed that those who received defibrillators had significantly lower all-cause (odds ratio [OR] 0.52; 95% confidence interval [CI] 0.45 to 0.60) and cardiovascular (OR 0.56; 95% CI 0.49 to 0.65)] rates of mortality at three years. No significant differences were noted between groups in their rates of noncardiovascular mortality (OR 0.92; 95% CI 0.77 to 1.10). Propensity score analysis demonstrated similar mortality reduction benefits at three years: risk ratio (RR) 0.72 (95% CI 0.69 to 0.79) for all-cause; RR 0.70 (95% CI 0.63 to 0.78) for cardiovascular; and RR 0.95 (95% CI 0.83 to 1.08) for noncardiovascular rates of mortality. These results suggest that one death is prevented in this patient population for every four to five patients receiving a defibrillator for three years. CONCLUSIONS: Implantable cardioverter-defibrillators in routine medical practice significantly reduce cardiovascular and all-cause rates of mortality at levels similar to secondary prevention trials.

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