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Biomedical subjects

William L Holman

Publications and source records attributed to William L Holman.

At least 19 recordsLinked to original sources
PubMed2007

Is early too early? Effect of shorter stays after bypass surgery.

BACKGROUND: Postoperative stays after coronary artery bypass graft surgery (CABG) decreased substantially in the 1990s. Although shorter stays offer clinical benefits, premature discharge could increase adverse events and offset initial savings. This study examined the effect of early discharge after CABG on readmission/death and cost within 60 days of discharge home. Variability in hospitals' tendencies for early discharge and adverse outcomes was also explored. METHODS: Analyses were based on clinical and claims data for 55,889 New York CABG patients discharged home 1995 to 1998. Early discharge was defined as a postoperative stay below the 15th percentile for patients with similar risk. The likelihood of early discharge and its effect on readmission/death were examined using hierarchical logistic regression, accounting for patient risk and within-hospital correlation. The correlation between early discharge and adverse outcomes at the hospital level was assessed. The effect of early discharge on subsequent inpatient, outpatient, skilled nursing, and home health costs was examined in the Medicare subset. RESULTS: Overall, 17% of patients were discharged early, with increasing prevalence over time. The tendency to discharge early varied widely among hospitals (2% to 42% of patients). We found no association between hospitals' tendencies for early discharge and adverse outcomes. Lower postdischarge costs among patients discharged early (mean = 3,491 dollars versus 5,246 dollars for typical stays) resulted in average cumulative savings of 6,309 dollars. CONCLUSIONS: Patients selected for earlier discharge after CABG did not have increased adverse event rates or higher costs. Variation among hospitals in early discharge suggests that more efficient patient management could be achieved at some hospitals.

Aged↗
PubMed2006

Trends in postoperative length of stay after bypass surgery.

BACKGROUND: Although single-site studies have reported reductions in coronary artery bypass graft (CABG) surgery length of stay (LOS) over the last 15 years, less information is available regarding overall temporal trends and interhospital variability. This study examined trends in postoperative LOS, associated rates of transfer at discharge and variation among hospitals in LOS at CABG hospitals in New York State. METHODS: Trends in postoperative LOS and transfers at discharge for 105,842 CABG patients treated in 30 hospitals in New York between 1992 and 1998 were first described graphically. Mixed models were then used to assess temporal trends and interhospital variability in LOS, accounting for differences in patient risk and within-hospital correlation in outcomes. Clinical and LOS data were obtained from the Cardiac Surgery Reporting System. Additional information was extracted from the New York Statewide Planning and Research Cooperative System. RESULTS: Postoperative LOS decreased 30% between 1992 and 1998 after adjusting for patient risk. A concurrent increase in the probability of nonacute patient transfers occurred over time, with the most pronounced increase in patients with stays exceeding 5 days. Underlying the downward trend in LOS was substantial interhospital variability that peaked in 1994 and remained significant in 1998. Stays were longer at hospitals located in New York City. CONCLUSIONS: The downward shift in LOS observed in the 1990s was achieved in part by an increase in nonacute care transfers, reflecting a shift in care setting. After decreasing trends in postoperative stays tapered off, significant variability among hospitals remained.

Aged↗
PubMed2006

Invited commentary.

Explore the source record for details and available documents.

Anastomosis, Surgical↗
PubMed2006

Native aortic valve insufficiency in patients with left ventricular assist devices.

Management of mild to moderate aortic insufficiency in patients with a left ventricular assist device remains controversial. We report 3 patients with aortic insufficiency and pulsatile left ventricular assist devices treated with a central aortic valve coapting suture. Two of the repairs have been durable for more than 1 year and aspirin appears to be sufficient anticoagulation.

Aged↗
PubMed2006

Mechanical circulatory support therapy as a bridge to transplant or recovery (new advances).

PURPOSE OF REVIEW: Large pulsatile left ventricular assist devices have been used as bridge-to-transplant therapy for the past 20 years. Over the past 2 years, a number of smaller rotary pumps have been introduced into clinical trials in the United States, Europe, and Australia. These devices offer the potential for smaller operations, greater resistance to infection, and new opportunities for bridge-to-recovery therapy. RECENT FINDINGS: Ongoing trials with axial flow devices support greater durability and less device-related infection than the HeartMate XVE (Thoratec Corporation, Pleasanton, California, USA). A greater tendency for pump thrombus and a higher anticoagulation requirement, however, are disadvantages compared with the HeartMate device. SUMMARY: Large pulsatile left ventricular assist devices have been the mainstay of mechanical support. The combination of durability and smaller pump size has become a focus of mechanical circulatory support in the current era. Ongoing clinical trials in the United States with three rotary pumps in both bridge-to-transplant and destination trials will likely result in a major increase in options for circulatory support. At least five other small, durable devices have recently entered non-US trials and are poised for clinical studies in the US. The National Institutes of Health-sponsored Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) will facilitate the introduction of new technology and study patient and device outcomes.

Assisted Circulation↗
PubMed2005

Mitochondrial dysfunction in cardiac ischemia-reperfusion injury: ROS from complex I, without inhibition.

A key pathologic event in cardiac ischemia reperfusion (I-R) injury is mitochondrial energetic dysfunction, and several studies have attributed this to complex I (CxI) inhibition. In isolated perfused rat hearts, following I-R, we found that CxI-linked respiration was inhibited, but isolated CxI enzymatic activity was not. Using the mitochondrial thiol probe iodobutyl-triphenylphosphonium in conjunction with proteomic tools, thiol modifications were identified in several subunits of the matrix-facing 1alpha sub-complex of CxI. These thiol modifications were accompanied by enhanced ROS generation from CxI, but not complex III. Implications for the pathology of cardiac I-R injury are discussed.

Animals↗
PubMed2005

Multiple treatment approach to limit cardiac ischemia-reperfusion injury.

BACKGROUND: This study evaluates a multiple treatment approach (ie, pharmacologic preconditioning [diazoxide], sodium-proton exchange inhibition [cariporide], and controlled reperfusion) to improve the outcome from severe cardiac ischemia-reperfusion injury that occurs during a cardiac operation. METHODS: Five groups of 10 pigs (group 1: control, group 2: diazoxide, group 3: cariporide, group 4: controlled reperfusion, and group 5: combination of diazoxide and cariporide-controlled reperfusion) underwent 75 minutes of left anterior descending occlusion, 1 hour of cardioplegic arrest, and 2 hours of reperfusion. Prior to occlusion, each group received an infusion of vehicle alone (ie, dimethylsulfoxide for the control and the controlled reperfusion groups) or vehicle with drug (ie, diazoxide or cariporide, or both for all other groups). Infarct size (primary outcome) was measured and was normalized to the region at risk. Regional function (secondary outcome) was measured using preload recruitable work area. RESULTS: Infarct size as a function of area at risk was decreased by cariporide-controlled reperfusion, and combination treatment compared with the control group (14 +/- 6%, 15 +/- 8%, and 9 +/- 4% vs 24 +/- 9%; p < 0.02), and variation in infarct size was decreased by combination treatment compared with the controlled reperfusion group alone (p < 0.02). Recovery of systolic function during reperfusion significantly improved in the left anterior descending region in the cariporide and combination groups compared with the control, controlled reperfusion, or diazoxide groups (group-time effect, p < 0.05). CONCLUSIONS: Combined use of controlled reperfusion, cariporide, and diazoxide decreases myocyte necrosis and loss of systolic function compared with an untreated control group. Combination treatment has the potential to improve the results of cardiac surgery, however further improvements are needed before clinical application.

Animals↗
PubMed2005

Invited commentary.

Explore the source record for details and available documents.

Equipment Design↗
PubMed2004

Outcomes of early extubation after bypass surgery in the elderly.

BACKGROUND: While early extubation after coronary artery bypass grafting (CABG) has been associated with resource savings, its effect on patient outcomes remains unclear. The goal of the present investigation was to evaluate whether early extubation can be performed safely in elderly CABG patients in community practice. METHODS: We studied 6,446 CABG patients, aged 65 years and older, treated at 35 hospitals between 1995 and 1998. Patients were categorized based on their post-CABG extubation duration (early, < 6 hours; intermediate, 6 to < 12 hours; and late, 12 to 24 hours). We compared unadjusted and risk-adjusted mortality, reintubation rates, and post-CABG length of stay (pLOS). We also examined the association between patients' intubation time and outcomes among patients with similar propensity for early extubation and among high-risk patient subgroups. RESULTS: The overall mean post-CABG intubation time was 9.8 (SD 5.7) hours with 29% of patients extubated within 6 hours. After adjusting for preoperative risk factors patients extubated in less than 6 hours had significantly shorter postoperative hospital stays than those with later extubation times. Patients extubated early also tended to have equal or better risk-adjusted mortality than those with intermediate (odds ratio: 1.69, p = 0.08) or long intubation times (odds ratio: 1.97, p = 0.02). These results were consistent among patients with similar preoperative propensity for early extubation and among important high-risk patient subgroups. There was no evidence for higher reintubation rates among elderly patients selected for early extubation. CONCLUSIONS: In community practice, early extubation after CABG can be achieved safely in selected elderly patients. This practice was associated with shorter hospital stays without adverse impact on postoperative outcomes.

Aged↗
PubMed2004

Left ventricular assist device performance with long-term circulatory support: lessons from the REMATCH trial.

BACKGROUND: Left ventricular assist device (LVAD) failure and malfunction rates are critical gauges for establishing LVADs as a long-term therapy for end-stage heart failure patients. These device performance measures, however, have been inadequately characterized in the bridge-to-transplantation literature. METHODS: REMATCH is a randomized trial that compares optimal medical management with LVAD implantation for patients with end-stage heart failure. An independent committee adjudicated patient outcomes. The primary endpoint--survival--was analyzed by intention to treat using the log-rank statistic. Frequency of event occurrence was analyzed by Poisson regression. The time to first event was analyzed by the product limit method. Device performance was disaggregated into confirmed malfunctions and system failures. The latter were events in which patients could not be rescued with backup circulatory support measures. RESULTS: The 1-year survival rate was 52% (95% confidence limit [CL]; 40%-63%) for LVAD patients versus 28% (95% CL; 17%-39%) for medical patients and the 2-year survival rate was 29% (95% CL; 19%-40%) for LVAD patients versus 13% (95% CL; 5%-22%) for medical patients. System failure was 0.13 per patient per year and the confirmed LVAD malfunction rate was 0.90. Freedom from device replacement was 87% at 1 year and 37% at 2 years. CONCLUSIONS: Despite the observed rates of device malfunction and replacement, LVAD implantation confers clinically significant improvement with regard to survival as compared with medical management. Device modifications and innovations for infection management exhibit great promise of improving device performance in the near future.

Aged↗
PubMed2004

Infection in permanent circulatory support: experience from the REMATCH trial.

BACKGROUND: This analysis of the REMATCH Trial focuses on infection, which was an important source of morbidity and mortality. We use the information to suggest ways to decrease the incidence and effects of device-related infection. METHODS: Patients were randomized prospectively to receive left ventricular assist devices (LVADs) or optimal medical management (OMM) for end-stage heart failure. Infection variables included sepsis adjudicated as the cause of death; sepsis reported as a serious adverse event; percutaneous site or pocket infection; and pump housing, inflow- or outflow-tract infection. We compared the incidence and prevalence of events between groups and generated time-related descriptions. RESULTS: Survival with LVAD (n=68 patients) was superior to OMM survival (n=61 patients) with a 47% decrease in risk of death (p <0.001), but the aggregate adverse event rate was greater for patients with LVADs (risk ratio, 2.29; 95% confidence interval, 1.85-2.84). Freedom from sepsis in patients with LVADs was 58% at 1 year and 48% at 2 years after implantation with superior survival in non-septic patients (60% vs 39% at 1 year and 38% vs 8% at 2 years in non-septic vs septic patients with LVADs, p <0.06). Percutaneous site or pocket infection did not affect survival (p=0.86). The hazard for onset of sepsis peaked within the first 3 weeks after implantation. CONCLUSIONS: Survival is improved with permanent LVAD implantation compared with OMM therapy. However, infection causes substantial morbidity and mortality. Decreasing infections will increase survival and decrease morbidity in permanent LVAD recipients and will improve the risk-benefit ratio for permanent LVAD therapy.

Antibiotic Prophylaxis↗
PubMed2004

Alabama coronary artery bypass grafting project: results from phase II of a statewide quality improvement initiative.

OBJECTIVE/BACKGROUND: This report describes the first round of results for Phase II of the Alabama CABG Project, a regional quality improvement initiative. METHODS: Charts submitted by all hospitals in Alabama performing CABG (ICD-9 codes 36.10-36.20) were reviewed by a Clinical Data Abstraction Center (CDAC) (preintervention 1999-2000; postintervention 2000-2001). Variables that described quality in Phase I were abstracted for Phase II and data describing the new variables of beta-blocker use and lipid management were collected. Data samples collected onsite by participating hospitals were used for rapid cycle improvement in Phase II. RESULTS: CDAC data (n = 1927 cases in 1999; n = 2001 cases in 2000) showed that improvements from Phase I in aspirin prescription, internal mammary artery use, and duration of intubation persisted in Phase II. During Phase II, use of beta-blockers before, during, or after CABG increased from 65% to 76% of patients (P < 0.05). Appropriate lipid management, an aggregate variable, occurred in 91% of patients before and 91% after the educational intervention. However, there were improvements in 3 of 5 subcategories for lipid management (documenting a lipid disorder [52%-57%], initiating drug therapy [45%-53%], and dietary counseling [74%-91%]; P < 0.05). CONCLUSIONS: In Phase II, this statewide process-oriented quality improvement program added two new measures of quality. Achievements of quality improvement from Phase I persisted in Phase II, and improvements were seen in the new variables of lipid management and perioperative use of beta-blockers.

Adrenergic beta-Antagonists↗
PubMed2003

Infection in ventricular assist devices: prevention and treatment.

Infection is one of the most important challenges to the use of implanted mechanical circulatory support systems (MCSS), particularly as we enter the era of permanent device use in patients who are not candidates for cardiac transplantation. This paper describes the pathogenesis of MCSS infection, with particular attention to the role of biofilm-forming bacteria. Suggestions are presented for the prevention and treatment of infections in implanted MCSS.

Heart Failure↗
PubMed2003

Intra-myocyte ion homeostasis during ischemia-reperfusion injury: effects of pharmacologic preconditioning and controlled reperfusion.

BACKGROUND: This study determines whether controlled reperfusion or diazoxide improves intramyocyte Na(+) homeostasis using a porcine model of severe ischemia-reperfusion injury. METHODS: Three groups (n = 10 pigs per group) had 75 minutes of left anterior descending artery occlusion during bypass. Group 1 had no treatment (control group), group 2 had controlled reperfusion (500 mL warm cardioplegia) (controlled reperfusion group), and group 3 had diazoxide (50 micromol/L before left anterior descending artery occlusion) (diazoxide group). Biopsies were taken from the left anterior descending artery region before ischemia and at 3, 5, and 10 minutes postreperfusion. Intra-myocyte Na(+) and water contents were determined using atomic absorption spectroscopy, and Na(+) concentrations were calculated. RESULTS: Intra-myocyte Na(+) increased for the diazoxide group pigs at 3-minutes postreperfusion (21.9 +/- 2.9 vs 34.0 +/- 3.4 micromol/mL; p = 0.02), but decreased to 19.9 +/- 3.2 micromol/mL at 10 minutes postreperfusion (p = 1.0 vs baseline). At 10 minutes postreperfusion, intra-myocyte Na(+) in the controlled reperfusion group was lower than baseline (22.3 +/- 2.7 vs 17.2 +/- 3.1 micromol/mL; p < 0.001). Intra-myocyte Na(+) at 10 minutes postreperfusion for the diazoxide and controlled reperfusion groups was lower than for the control group (p < 0.05). CONCLUSIONS: Diazoxide and controlled reperfusion improved intra-myocyte Na(+) homeostasis after severe ischemia-reperfusion injury.

Animals↗
PubMed2003

Hemodynamic evaluation of normally functioning Sulzer Carbomedics prosthetic valves.

The Sulzer Carbomedics prosthetic heart valve (CP) is a commonly used mechanical valve in clinical practice. In the present study, we used conventional and color Doppler echocardiography to assess the hemodynamics of normally functioning CP in the aortic (n = 73) and mitral (n = 127) positions. Our findings demonstrate no significant correlation of Doppler-measured peak and mean pressure gradients and effective orifice area with implanted valve size and actual orifice areas, measured directly by the manufacturer for CPs in both the mitral and aortic positions. However, it is still useful to measure effective orifice area by Doppler because a value in the normal or nonstenotic range points to an unobstructed prosthesis in the aortic or mitral position, in the absence of poor left ventricular ejection fraction. A value in the stenotic range could mean a normally functioning or obstructed prosthesis and, therefore, may need further investigation, such as assessment of valve leaflet motion by transthoracic or transesophageal echocardiography or fluoroscopy. Valve regurgitation as evaluated by color Doppler flow mapping was mild in practically all CPs in the aortic position, and in the majority of CPs in the mitral position.

Aortic Valve↗
PubMed2003

Modulation of mitochondrial adenosine triphosphate-sensitive potassium channels and sodium-hydrogen exchange provide additive protection from severe ischemia-reperfusion injury.

BACKGROUND: Preconditioning and inhibition of sodium-proton exchange attenuate myocardial ischemia-reperfusion injury by means of independent mechanisms that might act additively when used together. The hypothesis of this study is that treatment with a sodium-proton exchange inhibitor and a mitochondrial adenosine triphosphate-sensitive potassium channel opener produces superior functional recovery and a greater decrease in left ventricular infarct size compared with treatment with either drug alone in a model of severe global ischemia. METHODS: Isolated crystalloid-perfused rat hearts (n = 8 hearts per group) were administered vehicle (control, 0.04% dimethyl sulfoxide), diazoxide (100 micromol/L in 0.04% dimethyl sulfoxide), cariporide (10 micromol /L in 0.04% dimethyl sulfoxide), or diazoxide and cariporide before 40 minutes of ischemia at 35.5 degrees C to 36.5 degrees C and 30 minutes of reperfusion. RESULTS: The combination group had superior postischemic systolic function compared with that seen in the cariporide, diazoxide, and control groups (recovery of developed pressure: 91% +/- 7% vs 26% +/- 5%, 35% +/- 6%, and 16% +/- 3%, respectively; P <.05). Postischemic diastolic function in the combination group was superior compared with that seen in the other groups (change(pre-post) diastolic pressure of 67 +/- 4 mm Hg with control, 49 +/- 11 mm Hg with diazoxide, 59 +/- 10 mm Hg with cariporide, and 3 +/- 3 mm Hg with diazoxide and cariporide combination; P <.05). The left ventricular infarct area was less in the combination group compared with that in the cariporide, diazoxide, and control groups (6% +/- 2% vs 35% +/- 7%, 25% +/- 3%, and 37% +/- 9%, respectively; P <.05). CONCLUSIONS: Combining a selective mitochondrial adenosine triphosphate-sensitive potassium channel opener with a selective reversible inhibitor of sarcolemmal sodium-proton exchange improves recovery of contractile function from severe global ischemia in the isolated buffer-perfused rat heart. The putative mechanism for this benefit is superior protection of mitochondrial function.

Adenosine Triphosphate↗