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Kerry L Lee

Publications and source records attributed to Kerry L Lee.

At least 19 recordsLinked to original sources
PubMed2006

Cost-effectiveness of defibrillator therapy or amiodarone in chronic stable heart failure: results from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).

BACKGROUND: In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), implantable cardioverter-defibrillator (ICD) therapy significantly reduced all-cause mortality rates compared with medical therapy alone in patients with stable, moderately symptomatic heart failure, whereas amiodarone had no benefit on mortality rates. We examined long-term economic implications of these results. METHODS AND RESULTS: Medical costs were estimated by using hospital billing data and the Medicare Fee Schedule. Our base case cost-effectiveness analysis used empirical clinical and cost data to estimate the lifetime incremental cost of saving an extra life-year with ICD therapy relative to medical therapy alone. At 5 years, the amiodarone arm had a survival rate equivalent to that of the placebo arm and higher costs than the placebo arm. For ICD relative to medical therapy alone, the base case lifetime cost-effectiveness and cost-utility ratios (discounted at 3%) were dollar 38,389 per life-year saved (LYS) and dollar 41,530 per quality-adjusted LYS, respectively. A cost-effectiveness ratio < dollar 100,000 was obtained in 99% of 1000 bootstrap repetitions. The cost-effectiveness ratio was sensitive to the amount of extrapolation beyond the empirical 5-year trial data: dollar 127,503 per LYS at 5 years, dollar 88,657 per LYS at 8 years, and dollar 58,510 per LYS at 12 years. Because of a significant interaction between ICD treatment and New York Heart Association class, the cost-effectiveness ratio was dollar 29,872 per LYS for class II, whereas there was incremental cost but no incremental benefit in class III. CONCLUSIONS: Prophylactic use of single-lead, shock-only ICD therapy is economically attractive in patients with stable, moderately symptomatic heart failure with an ejection fraction < or = 35%, particularly those in NYHA class II, as long as the benefits of ICD therapy observed in the SCD-HeFT persist for at least 8 years.

Adult↗
PubMed2006

Cardiovascular outcomes with atrial-based pacing compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data.

BACKGROUND: Several randomized trials have compared atrial-based (dual-chamber or atrial) pacing with ventricular pacing in patients with bradycardia. No trial has shown a mortality reduction, and only 1 small trial suggested a reduction in stroke. The goal of this review was to determine whether atrial-based pacing prevents major cardiovascular events. METHODS AND RESULTS: A systematic review was performed of publications since 1980. For inclusion, trials had to compare an atrial-based with a ventricular-based pacing mode; use a randomized, controlled, parallel design; and have data on mortality, stroke, heart failure, or atrial fibrillation. Individual patient data were obtained from 5 of the 8 identified studies, representing 95% of patients in the 8 trials, and a total of 35 000 patient-years of follow-up. There was no significant heterogeneity among the results of the individual trials. There was no significant reduction in mortality (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.87 to 1.03; P=0.19) or heart failure (HR, 0.89; 95% CI, 0.77 to 1.03; P=0.15) with atrial-based pacing. There was a significant reduction in atrial fibrillation (HR, 0.80; 95% CI, 0.72 to 0.89; P=0.00003) and a reduction in stroke that was of borderline significance (HR, 0.81; 95% CI, 0.67 to 0.99; P=0.035). There was no convincing evidence that any patient subgroup received special benefit from atrial-based pacing. CONCLUSIONS: Compared with ventricular pacing, the use of atrial-based pacing does not improve survival or reduce heart failure or cardiovascular death. However, atrial-based pacing reduces the incidence of atrial fibrillation and may modestly reduce stroke.

Arrhythmias, Cardiac↗
PubMed2006

Treatment crossovers did not affect randomized treatment comparisons in the Mode Selection Trial (MOST).

OBJECTIVES: We evaluated the impact of treatment crossovers on study results in the Mode Selection Trial (MOST). BACKGROUND: The MOST study, a 2,010-patient, 6-year trial comparing dual-chamber pacing (DDDR) and ventricular pacing (VVIR) in sinus node dysfunction, demonstrated no difference in death or stroke and modest reductions in heart failure hospitalization (HFH) and atrial fibrillation (AF) with DDDR pacing. However, a moderate proportion of VVIR-randomized patients were temporarily or permanently crossed over to DDDR pacing. METHODS: Intent-to-treat (ITT) analyses compared treatment arms by randomized pacing mode. On-treatment analyses used time-dependent covariates to account for all crossovers. All analyses used Cox proportional hazards models and included covariates prespecified in the study design: age, gender, Charlson index, and prior stroke, heart failure, myocardial infarction, supraventricular tachyarrhythmia, and ventricular tachycardia or fibrillation. RESULTS: Of 996 VVIR-randomized patients, 375 (38%) were DDDR paced at some time, accounting for 27% of follow-up days among all VVIR-randomized patients. Of 1,014 DDDR-randomized patients, 53 (5%) were VVIR paced at some time, accounting for 1.5% of follow-up days among all DDDR-randomized patients. On-treatment analyses showed slightly lower hazard ratios favoring DDDR versus VVIR compared with ITT: death or stroke 0.88 (on-treatment) versus 0.91 (ITT); death 0.94 versus 0.95; stroke 0.74 versus 0.81; HFH 0.72 versus 0.73; and AF 0.72 versus 0.77. Interpretation of treatment effects was unchanged. CONCLUSIONS: Although treatment crossovers accounted for >25% of follow-up time in the VVIR-randomized group, this did not affect study results. End point comparisons between randomized modes are accurate reflections of DDDR versus VVIR pacing in this study population.

Aged↗
PubMed2006

Comparing classifications of death in the Mode Selection Trial: agreement and disagreement among site investigators and a clinical events committee.

Clinical events committees (CECs) are the current standard for endpoint adjudication in clinical trials. However, little data exist with which to compare CEC and site investigator determinations or to evaluate internal agreement among CEC members. Using data from the Mode Selection Trial in Sinus Node Dysfunction (MOST), we analyzed classifications of death in order to compare internal agreement among CEC physician reviewers and agreement between the CEC and site investigators. Death was classified at 2 levels: by major cause (cardiac, noncardiac, or unknown) and by minor subclassification of the major classifications. Reviewer agreement was tabulated at the major and minor levels, and standard and weighted kappa statistics were calculated. Disagreement at both levels was also determined. Individual decision-making was tabulated in terms of frequency in classifying death as unknown. All 404 deaths were classified by the CEC. Site investigators determined major classifications in 382 cases and minor classification in 379 cases. The CEC and the site investigators disagreed in classifying 41 cases (10.7%) at the major level and 117 (30.9%) at the minor level. CEC reviewers disagreed internally at the major level in 64 cases (15.8%), at the minor level in 63 cases (15.6%), and at any level in 127 cases (31.4%) (kappa = 0.60, 95% confidence interval (CI) [0.55, 0.66]; weighted kappa = 0.66, 95% CI [0.62, 0.75]). In resolving internal disagreements, the full CEC agreed with 1 of 2 CEC reviewers in 85.9% of cases. Disagreements occurred between site investigators and CEC reviewers in classifying deaths. Endpoint determination and decision-making varied among individual CEC reviewers, but second-tier reviews by the full CEC resolved all disagreements. These findings support continued use of CECs for endpoint adjudication in clinical trials.

Cause of Death↗
PubMed2006

Pacemaker implantation and quality of life in the Mode Selection Trial (MOST).

BACKGROUND: Dual-chamber pacemakers restore AV synchrony compared with ventricular pacemakers, but the effects on health-related quality of life (QOL) are uncertain. OBJECTIVES: The purpose of this study was to assess the effect of pacemaker implantation, clinical factors, and pacing mode on QOL. METHODS: The Mode Selection Trial (MOST) randomized 2,010 patients with sinus node dysfunction to rate-modulated right ventricular (VVIR) or dual-chamber (DDDR) pacing. A longitudinal analysis of serial QOL measures (Short Form-36 [SF-36], Specific Activity Scale, and time trade-off utility) was performed. In patients who crossed over from VVIR to DDDR because of severe pacemaker syndrome, the last known QOL prior to crossover was carried forward. RESULTS: Pacemaker implantation resulted in substantial improvement in almost all QOL measures. Subjects 75 years or older experienced significantly less improvement in functional status and physical component summary scores than did younger subjects. In longitudinal analyses of the effect of pacing mode on QOL, significant improvement in three SF-36 subscales was observed with DDDR pacing compared with VVIR pacing: role physical [62.8 points (95% confidence interval [CI] 60.2, 65.5) vs 56.4 (95% CI 53.7, 59.1)], role emotional [85.0 (95% CI 82.9, 87.0) vs 81.9 (95% CI 79.9, 84.0)], and vitality [51.8 (95% CI 50.3, 53.3) vs 49.3 (95% CI 47.8, 50.7)], but not in other SF-36 subscales, the Specific Activity Scale, or utilities. The gains in QOL were larger than the declines associated with 1 year of aging but smaller than those associated with heart failure. CONCLUSION: Pacemaker implantation improved health-related QOL. The mode selected was associated with much smaller, but significant, improvements in several domains, particularly role physical function.

Aged↗
PubMed2006

The association of the heart failure score with mortality and heart failure hospitalizations in elderly patients: insights from the Mode Selection Trial (MOST).

BACKGROUND: Patient and physician preferences as well as cost favor an increasingly higher threshold for hospital admission for heart failure (HF) treatment. This trend risks masking the severity and prevalence of HF as hospitalization for HF may decrease. METHODS: Heart Failure Score (HFS) has 4 ordinal subscales assessing (1) HF symptoms, physical signs of left (2) and (3) right HF, and (4) therapy changes for HF. Heart Failure Score was calculated for 1257 of 2010 (63%) patients enrolled in the MOST trial in sinus node dysfunction, who survived and had complete first-year HFS data at 4 postpacemaker implant visits (1, 3, 6, and 12 months). Heart Failure Score was summed and ranged from 0 to 14, with lower scores representing less HF. RESULTS: There were 1257 patients (median age 74 years [interquartile range 68-79], 47% were women, 61% had hypertension, 20%, diabetes mellitus, and 23%, prior myocardial infarction). The median HFS accumulated during 1 year was 4 (interquartile range 1-8). Of patients with a benign first year, those with a higher HFS were more likely to die during subsequent follow-up compared with patients with lower HFS (hazard ratio 1.07, 95% CI 1.04-1.10 for each 1-point increase, P < .001). CONCLUSIONS: Increasing HFS is associated with an increased risk of mortality in mostly elderly patients without pre-existing HF. Heart Failure Score may be a useful surrogate HF end point for clinical trials.

Aged↗
PubMed2006

Role of amiodarone or implantable cardioverter/defibrillator in patients with atrial fibrillation and heart failure.

BACKGROUND: Heart failure complicated by atrial fibrillation (AF) is associated with excessive mortality and morbidity. The aim of the study was to determine the role of amiodarone or implantable cardioverter/defibrillator (ICD) in patients with AF and heart failure. METHODS: Patients were determined to be in sinus rhythm (SR) or AF on the baseline electrocardiogram. Mortality, ICD discharge, or change in rhythm was assessed. RESULTS: Of the 2521 patients at baseline, 2328 were in SR and 173 were in AF. Overall, after adjusting for differences in baseline variables, there was no difference in mortality between patients with SR and patients with AF (P = .98), nor within assigned groups: placebo (P) (P = .82), amiodarone (A) (P = .68), and ICD (P = .40). For patients with SR, ICD decreased mortality (P vs ICD, P = .004; A vs ICD, P = .004; P vs A, P = .75). For patients with AF, there were no differences in mortality among groups (P vs ICD, P = .99; A vs ICD, P = .88; P vs A, P = .88). Of patients with SR at baseline, 11% (264) developed AF by any electrocardiogram during follow-up (P 12%, A 8%, ICD 15%; A vs P, P = .019; A vs ICD, P = .001; P vs ICD, P = .044). Of patients with AF, 70% (121) developed SR during follow-up (P 66%, A 67%, ICD 75%, all P = not significant against each other). Any ICD shock was seen in 52% (34) of patients with AF vs 30% (222) of patients with SR (P = .001). Inappropriate shocks were seen in 37% (24) of patients with AF vs 14% (107) of patients with SR (P = .001). Appropriate shocks were more often seen in AF vs SR (P = .03). CONCLUSION: After adjustments for baseline differences, patients with AF and patients with SR have similar overall mortality rates. Compared to P or A, ICD improves survival in patients with SR, but may not in patients with AF. Amiodarone is effective in reducing new AF, but not in converting AF to SR. Implantable cardioverter/defibrillator, inappropriate, and appropriate shocks were more often seen in AF than in SR.

Aged↗
PubMed2006

Selection of surgical or percutaneous coronary intervention provides differential longevity benefit.

BACKGROUND: Treatment of coronary artery disease (CAD) is evolving with better medications, improvements in percutaneous coronary intervention (PCI), and enhanced techniques for coronary artery bypass grafting (CABG). METHODS: In this study, 18,481 patients with significant (>75% stenosis) CAD treated at a single center between 1986 and 2000 were assigned to one of three groups based on initial treatment strategy: medical therapy (MED) (n = 6862), PCI (n = 6292), or CABG (n = 5327). Each group was categorized into 3 groups according to baseline severity of CAD: low-severity (predominantly 1-vessel), intermediate-severity (predominantly 2-vessel), and high-severity (all 3-vessel), and prospectively evaluated in Cox models for all-cause mortality adjusted for cardiac risk, comorbidity, and propensity for selection of a specific treatment. Treatments were compared for the entire period and three eras (1: 1986 to 1990; 2: 1991 to 1995; 3: 1996 to 2000), the last encompassing widespread availability of PCI with stenting. RESULTS: Survival significantly improved in all groups for all degrees of CAD, despite increasing severity of illness. Revascularization strategies provided significant survival over MED with 8.1, 10.6, and 23.6 additional months per 15 years of follow-up for low-severity, intermediate-severity, and high-severity CAD, respectively. Therapeutic improvements led to increased survival of 5.3 additional months per 7 years of follow-up (95% confidence interval, 0.2 to 10.2; p = 0.039) in era 3 for CABG compared with PCI for high-severity CAD. CONCLUSIONS: Initial revascularization strategies result in significant survival advantage over MED for all CAD levels. Patients with high-severity CAD have reduced survival with PCI compared with those initially treated with CABG.

Aged↗
PubMed2005

A new anatomic score for prognosis after cardiac catheterization in patients with previous bypass surgery.

OBJECTIVES: The purpose of this study was to determine the value of a new anatomic score for prognosis after diagnostic catheterization in patients with previous coronary artery bypass grafting (CABG). BACKGROUND: Previous CABG patients comprise a growing proportion of patients with coronary artery disease (CAD). Whereas prognostic scores are available to adjust for native CAD, there are no comparable scores for patients with previous CABG. METHODS: We studied 3,178 previous CABG patients (2,729 in a training set) who underwent cardiac catheterization. With a Cox model to develop relative weights in the training set, we created a graft index that adjusted native anatomy for territories with grafts free of significant (> or =75%) stenoses. Scaling the regression coefficients by the maximum coefficient created an index ranging from 0 to 100, where 100 was three-vessel CAD with no patent grafts. RESULTS: The graft index was significantly associated with all-cause death (chi-square = 121.9, p < 0.001). In combined models, the index was more strongly associated with all-cause death than either number of diseased vessels (chi-square = 68.0 and 1.7, respectively) or the Duke CAD index (chi-square = 54.3 and 9.5, respectively). In models for death using an independent validation set, the index was also associated more strongly than either native disease descriptors. In a model including other clinical variables, the graft index remained significantly associated with all-cause death (chi-square = 40.1, p < 0.001). CONCLUSIONS: For previous CABG patients, the Duke graft index was significantly more associated with prognosis than native anatomy alone and quantifies the effect of patent grafts on survival. This tool has the potential to help determine prognosis and inform the referral of post-CABG patients to repeat revascularization procedures.

Aged↗
PubMed2005

Association of prolonged QRS duration with death in a clinical trial of pacemaker therapy for sinus node dysfunction.

BACKGROUND: Prolonged QRS duration (QRSd) is an important prognostic indicator for death and heart failure hospitalization in patients with systolic heart failure. The relationship of baseline QRSd to death and heart failure hospitalization in patients with sinus node dysfunction who require pacemaker therapy is unknown. METHODS AND RESULTS: Baseline QRSd from 12-lead ECGs before pacemaker implantation were analyzed in the Mode Selection Trial (MOST), a 6-year, 2010-patient randomized trial of dual-chamber versus ventricular pacing in sinus node dysfunction. Baseline QRSd was > or =120 ms in 23.4% of patients and was associated with older age, lower ejection fraction, cardiomyopathy, and prior heart failure. Adjusted Cox models demonstrated baseline QRSd > or =120 ms was a strong independent predictor of death (hazard ratio [95% CI] 1.35 [1.07, 1.70], P=0.010) but not heart failure hospitalization. The risk of death increased with increased QRSd from 60 to 120 ms (P=0.002 and hazard ratio [95% CI] 1.14 [1.05, 1.23] for 10-ms increase in this range) after adjustment for other death predictors. CONCLUSIONS: Baseline QRSd > or =120 ms was associated with increased risk of death during pacemaker therapy for sinus node dysfunction.

Aged↗
PubMed2005

Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.

BACKGROUND: Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure (CHF). Treatment with amiodarone or an implantable cardioverter-defibrillator (ICD) has been proposed to improve the prognosis in such patients. METHODS: We randomly assigned 2521 patients with New York Heart Association (NYHA) class II or III CHF and a left ventricular ejection fraction (LVEF) of 35 percent or less to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD (829 patients). Placebo and amiodarone were administered in a double-blind fashion. The primary end point was death from any cause. RESULTS: The median LVEF in patients was 25 percent; 70 percent were in NYHA class II, and 30 percent were in class III CHF. The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent. The median follow-up was 45.5 months. There were 244 deaths (29 percent) in the placebo group, 240 (28 percent) in the amiodarone group, and 182 (22 percent) in the ICD group. As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5 percent confidence interval, 0.86 to 1.30; P=0.53) and ICD therapy was associated with a decreased risk of death of 23 percent (0.77; 97.5 percent confidence interval, 0.62 to 0.96; P=0.007) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. Results did not vary according to either ischemic or nonischemic causes of CHF, but they did vary according to the NYHA class. CONCLUSIONS: In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.

Aged↗
PubMed2005

Cost-effectiveness of dual-chamber pacing compared with ventricular pacing for sinus node dysfunction.

BACKGROUND: Compared with single-chamber ventricular pacing, dual-chamber pacing can reduce adverse events and, as a result, improve quality of life in patients paced for sick sinus syndrome. It is not clear, however, how these benefits compare with the increased cost of dual-chamber pacemakers. METHODS AND RESULTS: We used 4-year data from a 2010-patient, randomized trial to estimate the incremental cost-effectiveness of dual-chamber pacing compared with ventricular pacing and then projected these findings over the patients' lifetimes by using a Markov model that was calibrated to the first 5 years of in-trial data. To assess the stability of the findings, we performed 1000 bootstrap analyses and multiple sensitivity analyses. During the first 4 years of the trial, dual-chamber pacemakers increased quality-adjusted life expectancy by 0.013 year per subject at an incremental cost-effectiveness ratio of 53,000 dollars per quality-adjusted year of life gained. Over a lifetime, dual-chamber pacing was projected to increase quality-adjusted life expectancy by 0.14 year with an incremental cost-effectiveness ratio of approximately 6800 dollars per quality-adjusted year of life gained. In bootstrap analyses, dual-chamber pacing was cost-effective in 91.9% of simulations at a threshold of 50,000 dollars per quality-adjusted year of life and in 93.2% of simulations at a threshold of 100,000 dollars. Its cost-effectiveness ratio was also below this threshold in numerous sensitivity analyses that varied key estimates. CONCLUSIONS: For patients with sick sinus syndrome requiring pacing, dual-chamber pacing increases quality-adjusted life expectancy at a cost that is generally considered acceptable.

Aged↗
PubMed2005

Thrombolysis and counterpulsation to improve survival in myocardial infarction complicated by hypotension and suspected cardiogenic shock or heart failure: results of the TACTICS Trial.

BACKGROUND: Sustained hypotension, cardiogenic shock, and heart failure all imply a poor prognosis in acute myocardial infarction (MI). We assessed the benefit of adding 48 hours of intra-aortic balloon counterpulsation (IABP) to standard treatment for MI, in an international trial among hospitals without primary angioplasty capabilities. METHODS: We randomized 57 patients with MI complicated by sustained hypotension, possible cardiogenic shock, or possible heart failure to receive either fibrinolytic therapy and IABP or fibrinolysis alone. The primary end point was all-cause mortality at 6 months. RESULTS: In all, IABP was inserted in 27 of 30 assigned patients a median 30 minutes after fibrinolysis began and continued for a median 34 hours. Of the 27 patients assigned to fibrinolysis alone, 9 deteriorated such that IABP was required. The IABP group was at slightly higher risk at baseline, but the incidence of the primary end point did not differ significantly between groups (34% for combined treatment versus 43% for fibrinolysis alone; adjusted P = 0.23). Patients with Killip class III or IV showed a trend toward greater benefit from IABP (6-month mortality 39% for combined therapy versus 80% for fibrinolysis alone; P = 0.05). CONCLUSIONS: While early IABP use was not associated with a definitive survival benefit when added to fibrinolysis for patients with MI and hemodynamic compromise in this small trial, its use suggested a possible benefit for patients with the most severe heart failure or hypotension. ABBREVIATED ABSTRACT: We assessed the benefit of adding 48 hours of intra-aortic balloon counterpulsation to fibrinolytic therapy among 57 patients with acute myocardial infarction complicated by sustained hypotension, possible cardiogenic shock, or possible heart failure. The primary end point, mortality at 6 months, did not differ between groups (34% for combined treatment versus 43% for fibrinolysis alone [n = 27]; adjusted P = 0.23), although patients with Killip class III or IV did show a trend toward greater benefit from IABP (39% for combined therapy versus 80% for fibrinolysis; P = 0.05).

Aged↗
PubMed2005

Implantable cardioverter defibrillators and cardiac resynchronization therapy in patients with left ventricular dysfunction: randomized trial evidence through 2004.

Although many studies have shown that implantable cardioverter defibrillator (ICD) therapy improves the survival of patients with significant left ventricular dysfunction, the magnitude of effectiveness of ICD therapy in clinically defined subgroups remains uncertain. Similarly, although studies have shown an improvement in patients' hemodynamics and quality of life with cardiac resynchronization therapy (CRT), there is a continuing uncertainty about the effect of CRT on patients' survival and the magnitude of improvement in quality of life with this therapy. On August 24, 2004, an ad hoc group of experts representing clinical cardiovascular medicine, biostatistics, economics, and health policy were joined by representatives of the Food and Drug Administration, Centers for Medicare and Medicaid Services (Baltimore, Md), Agency for Healthcare Research and Quality (Rockville, Md), and the device industry for a 1-day round table to review the available clinical trial evidence on the effect of ICD therapy in the primary prevention of sudden cardiac death and the effect of CRT in patients with congestive heart failure. The meeting was organized by the Duke Clinical Research Institute, Durham, NC, and funded in part by the Agency for Healthcare Research and Quality. This document summarizes the evidence reviewed at that meeting and the discussions of that evidence.

Death, Sudden, Cardiac↗
PubMed2005

The PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) trial: study rationale, design, and baseline patient characteristics.

BACKGROUND: Coronary artery bypass graft (CABG) surgery with autologous vein graft (VG) conduit is one of the most frequently performed operations in the United States. Unfortunately, many VGs become occluded during long-term follow-up largely because of neointimal hyperplasia. A novel approach to preventing neointimal hyperplasia is with the double-stranded oligonucleotide edifoligide (Corgentech Inc, South San Francisco, Calif). Edifoligide inhibits E2F, a transcription factor that activates cell-cycle genes responsible for neointimal hyperplasia. METHODS: PREVENT IV is a phase-III, multicenter, randomized double-blind placebo-controlled trial of ex vivo treatment of autologous VGs with edifoligide in patients undergoing initial CABG surgery. The primary end point is VG failure, defined as death or > or =75% stenosis in a treated VG at 12- to 18-month angiographic follow-up. Secondary end points include major adverse cardiac events through at least 5 years and adverse events through 30 days. RESULTS: Enrollment of 3014 patients from 107 sites was completed on October 22, 2003. The baseline and procedural characteristics of the PREVENT IV population are generally well matched to a contemporary population of patients undergoing initial CABG from the Society of Thoracic Surgeons National Database. Angiographic follow-up is ongoing and scheduled to be completed in March 2005. CONCLUSIONS: The PREVENT IV data will establish whether VG pretreatment with an E2F transcription factor decoy, edifoligide, can improve graft patency and reduce the long-term morbidity and mortality of patients undergoing CABG surgery.

Aged↗
PubMed2005

Heart failure hospitalization is more common in pacemaker patients with sinus node dysfunction and a prolonged paced QRS duration.

OBJECTIVES: The purpose of this study was to determine whether a prolonged paced QRS duration increases the risk of cardiac dysfunction. BACKGROUND: Right ventricular apical pacing mimics left bundle branch block, results in a prolonged QRS duration of variable duration, and causes ventricular desynchronization. METHODS: In the Mode Selection Trial (MOST), QRS duration was measured in patients who had at least one paced ventricular complex recorded on 12-lead ECG within 3 months of enrollment (early) and after 9 months (late). Clinical endpoints including heart failure hospitalization, mortality, and atrial fibrillation were analyzed. A total of 1,026 patients were included in the analysis. Median age was 75 years (25th, 75th percentiles = 69, 80) and median ejection fraction prior to implant was 55% (45, 60). The cumulative percent ventricular pacing (DDDR and VVIR) was 81% over a median follow-up of 33 months. During period, 123 patients had heart failure hospitalization, 197 died, and 261 patients had atrial fibrillation. RESULTS: Cox proportional hazards models demonstrated that paced QRS duration was a strong predictor of heart failure hospitalization (hazard ratio 1.15; 95% confidence interval 1.07,1.23) for each 10-ms increase in paced QRS duration (P = .001). The increased risk was unaffected by adjustment for other known predictors of heart failure hospitalization in the study. Paced QRS duration was not significant for mortality (P = .41) or atrial fibrillation (P = .20) when baseline QRS duration and other predictors were included. CONCLUSIONS: Paced QRS duration is a significant, independent predictor of heart failure hospitalization in patients with sinus node dysfunction. A very long paced QRS duration is associated with increased heart failure hospitalization.

Aged↗
PubMed2005

Clinical and quality of life comparison of accelerometer, piezoelectric crystal, and blended sensors in DDDR-paced patients with sinus node dysfunction in the mode selection trial (MOST).

INTRODUCTION: Permanent pacemakers are capable of increasing heart rate in response to physical activity by a variety of sensors including accelerometers, piezoelectric crystals, or blended sensors. The impact of these different physiologic sensors on cardiovascular events and quality of life is not known. METHODS: Of 2,010 patients randomized in the Mode Selection Trial, 1,245 patients were selected with the most commonly used pacemakers with these three sensors. Clinical characteristics and quality of life were compared between groups at baseline, 3 months, and then yearly. RESULTS: There were 449 patients with an accelerometer sensor device, 682 with a piezoelectric sensor, and 114 with a blended sensor. The groups were similar in terms of age (mean 74 years), gender, and cardiac risk factors but differences existed in weight, heart rate, mitral regurgitation, revascularization history, and drug therapy. The median ventricular pacing frequency was 80% (25th, 75th percentiles 42, 97). After a median follow-up of 33.1 months, the risk of death, heart failure hospitalization, atrial fibrillation, and the combined endpoint of mortality and stroke was not significantly different between the sensor types, after adjustment for baseline differences. Quality of life analyses demonstrated that patients with blended sensors had significantly worse (P < 0.01) physical function than did patients with the other two sensor systems. Moreover, patients receiving blended sensors had the poorest absolute scores, without reaching statistical significance, on 9 of 13 quality of life measures after adjusting for differences in the groups. CONCLUSION: We found no significant differences among the three most utilized sensors in clinical endpoints. Those patients who received blended sensors had worse physical function quality of life scores. However, clinical selection of the most sophisticated sensor for the most ill patients cannot be excluded as an explanation of these results.

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