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Biomedical subjects

Leslie A Saxon

Publications and source records attributed to Leslie A Saxon.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of sudden cardiac death and appropriate shock in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Trial.

BACKGROUND: The factors that determine the risk for sudden death or implantable cardioverter defibrillator therapy in patients receiving cardiac resynchronization therapy (CRT) therapies are largely unknown. METHODS AND RESULTS: We hypothesized that clinical measures of heart failure severity and the presence of comorbid conditions would predict the risk of malignant arrhythmias in the 1520 patients enrolled in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Trial. Outcomes in the CRT group after implantable cardioverter defibrillator therapy were also evaluated. The CRT-defibrillator device reduced the risk of sudden death by 56% compared with drug therapy (17 of 595 [2.9%] versus 18 of 308 [5.8%], P<0.02). CRT therapy was not associated with sudden death risk reduction (48 of 617 [7.8%]). Other factors associated with reduced sudden death risk were left ventricular ejection fraction >20% (HR, 0.55 [95% CI, 0.35 to 0.87]; P=0.01), QRS duration >160 ms (HR, 0.63 [95% CI, 0.40 to 0.997]; P=0.05), and female gender (HR, 0.56 [95% CI, 0.34 to 0.94]; P=0.003). The risk for sudden death was increased by advanced New York Heart Association class IV heart failure (HR, 2.62 [95% CI, 1.61 to 4.26]; P<0.011) and renal dysfunction (HR, 1.69 [95% CI, 1.06 to 2.69]; P=0.03). An appropriate shock was experienced in 88 (15%) of the 595 CTR-D patients. In the CRT-defibrillator patients, female gender (HR, 0.54 [95 % CI, 0.31 to 0.94]; P=0.03) and use of neurohormonal antagonists were associated with reduced risk. Class IV heart failure status increased risk. Appropriate implantable cardioverter defibrillator therapy was positively associated with risk of death or all-cause hospitalization (HR, 1.57; P<0.002), pump failure death or hospitalization (HR, 2.35; P<0.001), and sudden death (HR, 2.99; P=0.03), but not total mortality (HR, 1.3; P=0.28). CONCLUSIONS: In CRT candidates, sudden cardiac death risk is associated with higher New York Heart Association class and renal dysfunction. In CRT-defibrillator recipients, reduction in the risk of an appropriate shock is associated with medical therapy with neurohormonal antagonists, female gender, and New York Heart Association functional class III versus IV clinical status. Shock therapy was associated with worse outcome.

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PubMed2006

Results of the multicenter RENEWAL 3 AVT clinical study of cardiac resynchronization defibrillator therapy in patients with paroxysmal atrial fibrillation.

INTRODUCTION: Atrial fibrillation impacts the clinical course of up to 50% of patients with advanced heart failure (HF) who are eligible for cardiac resynchronization therapy with a defibrillator (CRT-D). While RV-based defibrillators are available with advanced atrial diagnostics and therapies that provide rapid diagnosis and treatment of spontaneously occurring atrial tachycardia/fibrillation (AT/AF) episodes, there is no CRT-D device that combines atrial/ventricular and CRT therapies. PURPOSE: The purpose of the prospective multicenter RENEWAL 3 AVT study is to assess the performance of atrial diagnostics and therapies used in combination with a CRT-D device. METHODS: Enrolled patients were required to have indications for a CRT-D device and a documented episode of AT/AF within 12 months of enrollment. A total of 170 patients were enrolled over 9 months (85% male; mean age 72 +/- 10 years; NYHA classification: 88% III, 12% IV; left ventricular ejection fraction [LVEF] mean 23 +/- 6%; mean QRS duration 150 +/- 25 msec; 78% ischemic etiology). The documented atrial arrhythmia was AF in 77% of patients. A total of 60% of patients had the CRT-D device placed for primary prevention of sudden death and 40% of patients had a history of ventricular arrhythmia in addition to HF. The device operates in the biventricular (BiV) triggered mode for sensed ventricular events associated with AF. RESULTS: A total of 159 patients (95%) had a successful CRT-D implant. Over a mean follow-up of 5.7 +/- 2.3 months, there were a total of 152 atrial shocks delivered in 108 patients for induced (93%) or spontaneous (7%) occurring episodes of AF. Spontaneously occurring AF was observed in 40 patients (25%). The rate of first shock conversion was 118/152 (78%, mean energy 11.6 +/- 5.9 J). Overall shock therapy conversion rate was 138/152 (91%). The number of shock conversions resulting in sinus rhythm maintained for at least 2 minutes postshock was 87% for induced episodes. Therapy was delivered for spontaneous ventricular tachycardia/fibrillation in nine patients (6%). There was no instance of ventricular proarrhythmia associated with atrial shock therapies, undersensing of ventricular arrhythmias, or interruption of CRT therapy associated with the combined device. CONCLUSIONS: In CRT-D candidates with a history of AF, 25% experience recurrent AF within 6 months of implant. Atrial detection and ventricular detection, shock, and resynchronization therapies are not compromised by the addition of atrial therapies to a CRT-D device.

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PubMed2005

Septal to posterior wall motion delay fails to predict reverse remodeling or clinical improvement in patients undergoing cardiac resynchronization therapy.

OBJECTIVES: The aim of this study was to test the hypothesis that a longer septal-to-posterior wall motion delay (SPWMD) would predict greater reverse remodeling and an improved clinical response in heart failure patients randomized to cardiac resynchronization therapy (CRT) in the CONTAK-CD trial. BACKGROUND: The SPWMD predicted clinical benefit with CRT in two previous studies from the same center. METHODS: In this retrospective analysis of the CONTAK-CD trial, SPWMD was measured from the baseline echocardiogram of 79 heart failure patients (ejection fraction 22 +/- 7%, QRS duration 159 +/- 27 ms, 72% ischemic, 84% male) randomized to CRT and compared with six-month changes in echocardiographic and clinical parameters. Patients with a left ventricular end-systolic volume index (LVESVI) reduction of at least 15% were considered responders. RESULTS: The feasibility and reproducibility of performing the SPWMD measurements were poor. Larger values for SPWMD did not correlate with six-month changes in left ventricular end-diastolic volume index (p = 0.26), LVESVI (p = 0.41), or left ventricular ejection fraction (p = 0.36). Responders did not have a significantly different SPWMD than non-responders (p = 0.26). The SPWMD did not correlate with measures of clinical improvement. At a threshold of SPWMD >130 ms, the test characteristics to predict reverse remodeling or a clinical response were inadequate. CONCLUSIONS: The previous findings that SPWMD predicts reverse remodeling or clinical improvement with CRT were not reproducible in patients randomized in the CONTAK-CD trial.

Aged↗
PubMed2005

Cost effectiveness of cardiac resynchronization therapy in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial.

OBJECTIVES: The analysis goal was to estimate incremental cost-effectiveness ratios (ICERs) for the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial patients who received cardiac resynchronization therapy (CRT) via pacemaker (CRT-P) or pacemaker-defibrillator (CRT-D) in combination with optimal pharmacological therapy (OPT) relative to patients with OPT alone. BACKGROUND: In the COMPANION trial, CRT-P and CRT-D reduced the combined risk of all-cause mortality or first hospitalization among patients with advanced heart failure and intraventricular conduction delays, but the cost effectiveness of the therapy remains unknown. METHODS: In this analysis, intent-to-treat trial data were modeled to estimate the cost effectiveness of CRT-D and CRT-P relative to OPT over a base-case seven-year treatment episode. Exponential survival curves were derived from trial data and adjusted by quality-of-life trial results to yield quality-adjusted life-years (QALYs). For the first two years, follow-up hospitalizations were based on trial data. The model assumed equalized hospitalization rates beyond two years. Initial implantation and follow-up hospitalization costs were estimated using Medicare data. RESULTS: Over two years, follow-up hospitalization costs were reduced by 29% for CRT-D and 37% for CRT-P. Extending the cost-effectiveness analysis to a seven-year base-case time period, the ICER for CRT-P was 19,600 dollars per QALY and the ICER for CRT-D was 43,000 dollars per QALY relative to OPT. CONCLUSIONS: For the COMPANION trial patients, the use of CRT-P and CRT-D was associated with a cost-effectiveness ratio below generally accepted benchmarks for therapeutic interventions of 50,000 dollars per QALY to 100,000 dollars per QALY. This suggests that the clinical benefits of CRT-P and CRT-D can be achieved at a reasonable cost.

Cardiac Output, Low↗
PubMed2005

A comparison of cardiac resynchronization by sequential biventricular pacing and left ventricular pacing to simultaneous biventricular pacing: rationale and design of the DECREASE-HF clinical trial.

BACKGROUND: The first generation of cardiac resynchronization therapy (CRT) devices approved for the treatment of heart failure used simultaneous biventricular (BiV) pacing to achieve ventricular resynchronization. Left ventricular pacing alone and sequential BiV pacing also show promise as alternative ways to deliver CRT, but have not been studied together in a large randomized trial. METHODS: The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure (DECREASE-HF) Trial is a randomized, double-blind, 3-arm study of patients in New York Heart Association Class III or IV with an ejection fraction of 35% or less and a QRS duration > or =150 ms. Patients are randomized to receive either left ventricular pacing, simultaneous BiV pacing, or sequential BiV pacing. CONCLUSION: The study uses a novel composite endpoint that combines peak oxygen consumption and left ventricular end systolic dimension, thus combining a measure of symptomatic improvement (peak oxygen consumption) with a physiologic measure of ventricular reverse remodeling (left ventricular end systolic dimension) into a single composite score. Additionally, the safety and effectiveness of the CONTAK RENEWAL 2/4/4HE/EASYTRAK 2 system will be evaluated using: heart failure-related adverse events; system-related complications; left ventricular lead-related complications; detection time of induced ventricular fibrillation; and left ventricular lead performance (pacing threshold, pacing impedance, and R-wave amplitude).

Cardiac Output↗
PubMed2005

Sudden cardiac death: epidemiology and temporal trends.

Sudden cardiac death (SCD) now accounts for more than half of all coronary heart disease deaths in the United States. The majority of cases are due to underlying coronary artery disease, and deaths from both coronary artery disease and SCD have declined markedly over the past several decades due to improved primary and secondary prevention and treatment strategies. This review examines the current statistics on the prevalence of SCD, and identifies those patients at greatest risk. It also discusses existing tests and treatments, including medication that results in neurohormonal antagonism, and devices such as the implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy with a defibrillator (CRT-D). Along with increased public awareness of SCD as a major health risk, physicians are advised to implement proven effective drug and devices that can improve survival.

Death, Sudden, Cardiac↗
PubMed2004

Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure.

BACKGROUND: We tested the hypothesis that prophylactic cardiac-resynchronization therapy in the form of biventricular stimulation with a pacemaker with or without a defibrillator would reduce the risk of death and hospitalization among patients with advanced chronic heart failure and intraventricular conduction delays. METHODS: A total of 1520 patients who had advanced heart failure (New York Heart Association class III or IV) due to ischemic or nonischemic cardiomyopathies and a QRS interval of at least 120 msec were randomly assigned in a 1:2:2 ratio to receive optimal pharmacologic therapy (diuretics, angiotensin-converting-enzyme inhibitors, beta-blockers, and spironolactone) alone or in combination with cardiac-resynchronization therapy with either a pacemaker or a pacemaker-defibrillator. The primary composite end point was the time to death from or hospitalization for any cause. RESULTS: As compared with optimal pharmacologic therapy alone, cardiac-resynchronization therapy with a pacemaker decreased the risk of the primary end point (hazard ratio, 0.81; P=0.014), as did cardiac-resynchronization therapy with a pacemaker-defibrillator (hazard ratio, 0.80; P=0.01). The risk of the combined end point of death from or hospitalization for heart failure was reduced by 34 percent in the pacemaker group (P<0.002) and by 40 percent in the pacemaker-defibrillator group (P<0.001 for the comparison with the pharmacologic-therapy group). A pacemaker reduced the risk of the secondary end point of death from any cause by 24 percent (P=0.059), and a pacemaker-defibrillator reduced the risk by 36 percent (P=0.003). CONCLUSIONS: In patients with advanced heart failure and a prolonged QRS interval, cardiac-resynchronization therapy decreases the combined risk of death from any cause or first hospitalization and, when combined with an implantable defibrillator, significantly reduces mortality.

Adrenergic beta-Antagonists↗
PubMed2003

Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias.

OBJECTIVES: This study was conducted to assess the safety and effectiveness of cardiac resynchronization therapy (CRT) when combined with an implantable cardioverter defibrillator (ICD). BACKGROUND: Long-term outcome of CRT was measured in patients with symptomatic heart failure (HF), intraventricular conduction delay, and malignant ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) requiring therapy from an ICD. METHODS: Patients (n = 490) were implanted with a device capable of providing both CRT and ICD therapy and randomized to CRT (n = 245) or control (no CRT, n = 245) for up to six months. The primary end point was progression of HF, defined as all-cause mortality, hospitalization for HF, and VT/VF requiring device intervention. Secondary end points included peak oxygen consumption (VO(2)), 6-min walk (6 MW), New York Heart Association (NYHA) class, quality of life (QOL), and echocardiographic analysis. RESULTS: A 15% reduction in HF progression was observed, but this was statistically insignificant (p = 0.35). The CRT, however, significantly improved peak VO(2) (0.8 ml/kg/min vs. 0.0 ml/kg/min, p = 0.030) and 6 MW (35 m vs. 15 m, p = 0.043). Changes in NYHA class (p = 0.10) and QOL (p = 0.40) were not statistically significant. The CRT demonstrated significant reductions in ventricular dimensions (left ventricular internal diameter in diastole = -3.4 mm vs. -0.3 mm, p < 0.001 and left ventricular internal diameter in systole = -4.0 mm vs. -0.7 mm, p < 0.001) and improvement in left ventricular ejection fraction (5.1% vs. 2.8%, p = 0.020). A subgroup of patients with advanced HF (NYHA class III/IV) consistently demonstrated improvement across all functional status end points. CONCLUSIONS: The CRT improved functional status in patients indicated for an ICD who also have symptomatic HF and intraventricular conduction delay.

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PubMed2003

Isolated bundle branch block and left ventricular dysfunction.

BACKGROUND: Population studies have identified the presence of bundle branch block (BBB) as a risk factor for increased mortality in patients with known cardiac disease. It is unknown how chronic ventricular dyssynchrony resulting solely from conduction delay affects ventricular function. METHODS AND RESULTS: Subjects were retrospectively identified from the University of California, San Francisco, electrocardiogram database with QRS prolongation. Subjects who had no evidence of heart disease and had baseline and serial studies evaluating ongoing risk of coronary artery disease status and left ventricular function were followed over time. Documentation of a minimum of 2 serial evaluations of cardiac status were present in a total of 51/176 (20%) subjects with isolated BBB who constitute the study population. After a mean follow-up of 52 +/- 45 months-adjusting for differences due to age, sex, the presence of hypertension, hyperlipidemia, and diabetes mellitus-left ventricular ejection fraction diminished by -7.3 +/- 12% per year in the isolated left BBB cohort versus -1.9 +/- 4% in isolated right BBB cohort and -1.1 +/- 3% reduction in the isolated nonspecific intraventricular conduction delay cohort (P =.019). CONCLUSIONS: Left bundle branch block itself may be a cause of ventricular dysfunction.

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PubMed2002

Effects of long-term biventricular stimulation for resynchronization on echocardiographic measures of remodeling.

BACKGROUND: Long-term ventricular resynchronization therapy improves symptom status. Changes in left ventricular remodeling have not been adequately evaluated. METHODS AND RESULTS: Fifty-three patients with systolic heart failure and bundle-branch block underwent implantation of biventricular stimulation (BVS) devices as part of a randomized trial. Echocardiograms were acquired at randomization and at 6-week intervals until completion of 12 weeks of continuous BVS. There were no changes in heart rate or QRS duration after 12 weeks of BVS. Serum norepinephrine values did not change with BVS. After 12 weeks of BVS, left atrial volume decreased. Left ventricular end-systolic and end-diastolic dimensions and left ventricular end-systolic volume also decreased after 12 weeks of BVS. Sphericity index did not change. Measures of systolic function, including left ventricular outflow tract and aortic velocity time integral and myocardial performance index, improved. CONCLUSIONS: Long-term resynchronization therapy results in atrial and ventricular reverse remodeling and improved hemodynamics.

Adult↗
PubMed2002

Heart failure and Implantable Cardioverter Defibrillator (ICD) therapy: Update and perspective on current primary prevention trials.

BACKGROUND: Recently completed studies have evaluated the role of the Implantable Cardioverter Defibrillator (ICD) in extending life in the letting of left ventricular dysfunction. METHODS AND RESULTS: All major primary prevention ICD trials performed in the United States are reviewed. CONCLUSIONS: Data to date supports the use of the ICD for primary prevention of sudden death in the setting of ischemic left ventricular dysfunction. Data is lacking in an advanced heart failure population and in patients with nonischemic cardiomyopathy.

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