Sacral neuromodulation versus onabotulinumtoxinA for refractory urgency urinary incontinence: impact on fecal incontinence symptoms and sexual function.

BACKGROUND: Women with refractory urgency urinary incontinence can be treated with onabotulinumtoxinA or sacral neuromodulation. Little data exists on the comparative effects of treatment of refractory urgency urinary incontinence on other pelvic floor complaints, such as bowel and sexual function. OBJECTIVE: The objective of this study was to compare the impact of these treatments on fecal incontinence and sexual symptoms. METHODS: This was a planned supplemental analysis of a randomized trial in women with refractory urgency urinary incontinence treated with onabotulinumtoxinA (n = 190) or sacral neuromodulation (n = 174). Fecal incontinence and sexual symptoms were assessed at baseline and at 6, 12, and 24 months. Fecal incontinence symptoms were measured using the St Mark's (Vaizey) Fecal Incontinence severity scale. Sexual symptoms were measured using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) and the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). The PISQ-IR allows measurement of sexual symptoms in both sexually active and non-sexually active adults. Primary outcomes were change in Vaizey and PISQ-12 scores between baseline and 6 months. Secondary outcomes were change in PISQ-IR total and subscores between baseline and 6 months and change in Vaizey, PISQ-12, and PISQ-IR scores between baseline and 12 and 24 months. Intent-to-treat analysis was performed using repeated measures mixed model to estimate change in all parameters from baseline while adjusting for the baseline score. A subgroup analysis of women with clinically significant bowel symptoms was conducted based on baseline Vaizey score of ≥12. RESULTS: At baseline, mean Vaizey scores were indicative of mild fecal incontinence symptoms and were not different between onabotulinumtoxinA and sacral neuromodulation groups (7.6 ± 5.3 vs 6.6 ± 4.9, P = .07). The proportion of sexually active women (56% vs 63%, P = .25), mean PISQ-12 score (33.4 ± 7.5 vs 32.7 ± 6.7, P = .55), or PISQ-IR subscores were also not different between the onabotulinumtoxinA and sacral neuromodulation groups at baseline. There was no difference between women treated with onabotulinumtoxinA and those treated with sacral neuromodulation at 6 months in terms of improvement in fecal incontinence symptom score (Vaizey: -1.9, 95% confidence interval -2.6 to -1.2 vs -0.9, 95% confidence interval -1.7 to -0.2, P = .07) or sexual symptoms score (PISQ-12: 2.2, 95% confidence interval 0.7 to 3.7 vs 2.2, 95% confidence interval 0.7 to 3.7, P = .99). There was no difference in improvement between groups in the sexual symptom subscores in sexually active and non-sexually active women at 6 months. Similar findings were noted at 12 and 24 months. In a subgroup (onabotulinumtoxinA = 33 and sacral neuromodulation = 22) with clinically significant fecal incontinence at baseline (Vaizey score ≥12), there was a clinically meaningful improvement in symptoms in both groups from baseline to 6 months, with no difference in improvement between the onabotulinumtoxinA and sacral neuromodulation groups (-5.1, 95% confidence interval -7.3 to -2.8 vs -5.6, 95% confidence interval -8.5 to -2.6, P = .8). CONCLUSION: There were no differences in improvement of fecal incontinence and sexual symptoms in women with urgency urinary incontinence treated with onabotulinumtoxinA or sacral neuromodulation. Women with significant fecal incontinence symptoms at baseline had clinically important improvement in symptoms, with no difference between the treatments. Our findings can help clinicians counseling women considering treatment for refractory urgency urinary incontinence.

Surgical revascularization is associated with maximal survival in patients with ischemic mitral regurgitation: a 20-year experience.

BACKGROUND: The optimal treatment for ischemic mitral regurgitation remains actively debated. Our objective was to evaluate the relationship between ischemic mitral regurgitation treatment strategy and survival. METHODS AND RESULTS: We retrospectively reviewed patients at our institution diagnosed with significant coronary artery disease and moderate or severe ischemic mitral regurgitation from 1990 to 2009, categorized by medical treatment alone, percutaneous coronary intervention, coronary artery bypass grafting (CABG), or CABG plus mitral valve repair or replacement. Kaplan-Meier methods and multivariable Cox proportional hazards analyses were performed to assess the relationship between treatment strategy and survival, with the use of propensity scores to account for nonrandom treatment assignment. A total of 4989 patients were included: medical treatment alone=36%, percutaneous coronary intervention=26%, CABG=33%, and CABG plus mitral valve repair or replacement=5%. Median follow-up was 5.37 years. Compared with medical treatment alone, significantly lower mortality was observed in patients treated with percutaneous coronary intervention (adjusted hazard ratio, 0.83; 95% confidence interval, 0.76-0.92; P=0.0002), CABG (adjusted hazard ratio, 0.56; 95% confidence interval, 0.51-0.62; P<0.0001), and CABG plus mitral valve repair or replacement (adjusted hazard ratio, 0.69; 95% confidence interval, 0.57-0.82; P<0.0001). There was no significant difference in these results based on mitral regurgitation severity. CONCLUSIONS: Patients with significant coronary artery disease and moderate or severe ischemic mitral regurgitation undergoing CABG alone demonstrated the lowest risk of death. CABG with or without mitral valve surgery was associated with lower mortality than either percutaneous coronary intervention or medical treatment alone.

Persistence with secondary prevention medications after acute myocardial infarction: Insights from the TRANSLATE-ACS study.

BACKGROUND: Persistent use of secondary prevention therapies after acute myocardial infarction (MI) is critical to optimizing long-term outcomes. METHODS: Medication persistence was assessed among 7,955 MI patients in 216 hospitals participating in the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome study from 2010 to 2012. Persistence was defined as continuation of aspirin, adenosine diphosphate receptor inhibitors, ß-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins from discharge to 6 months post-MI. Multivariable logistic regression modeling was used to determine factors associated with nonpersistence, defined as <80% persistence with all medication classes. RESULTS: Overall, 31% of MI patients stopped taking a least 1 medication by 6 months. The most common reasons cited for medications discontinuation were side effects and physician instruction (57%), whereas financial concerns were cited in 8% overall. After multivariable modeling, black race (odds ratio 1.36, 95% CI 1.15-1.62), older age (odds ratio 1.07, 95% CI 1.02-1.12), atrial fibrillation (odds ratio 1.67, 95% CI 1.33-2.09), dialysis (odds ratio 1.79, 95% CI 1.15-2.78), and depression (odds ratio 1.22, 95% CI 1.02-1.45) were associated with lower likelihood of persistence. Private insurance (odds ratio 0.85, 95% 0.76-0.95), prescription cost assistance (odds ratio 0.63, 95% CI 0.54-0.75), and outpatient follow-up arranged before discharge (odds ratio 0.89, 95% CI 0.80-0.99) were associated with higher persistence. CONCLUSIONS: Nearly one-third of MI patients are no longer persistent with their prescribed medications by 6 months. Patients at high risk for nonpersistence may be identified by clinical and sociodemographic features. These observations underscore key opportunities to optimize longitudinal use of secondary prevention therapies.

Relationship of the time interval between cardiac catheterization and elective coronary artery bypass surgery with postprocedural acute kidney injury.

BACKGROUND: Some prior studies have suggested that the time to cardiac surgery after cardiac catheterization is inversely related to postoperative acute kidney injury (AKI). However, these studies, because of the small number of patients, were unable to adequately account for patient case-mix and included both those undergoing elective surgery and those undergoing urgent surgery. METHODS AND RESULTS: We examined data on 2441 consecutive patients undergoing elective coronary artery bypass surgery (CABG) after cardiac catheterization. The association of post-CABG AKI (defined as increase in post-CABG serum creatinine ≥ 50% above baseline or the need for new dialysis) and time between cardiac catheterization and CABG was evaluated using multivariable logistic regression modeling. AKI occurred in 17.1% of CABG patients. The risk of AKI was highest in patients in whom CABG was performed ≤ 1 day after cardiac catheterization (adjusted mean rates [95% CI]: 24.0% [18.0%, 30.9%], 18.4% [14.8%, 22.5%], 17.3% [13.3%, 21.9%], 16.4% [12.6%, 20.8%], and 15.8% [13.7%, 18.0%] for days ≤ 1, 2, 3, 4, and ≥ 5, respectively; P=0.019 for test of trend). Post-CABG AKI was associated with increased risk of long-term death (hazard ratio 1.268, 95% CI 1.093, 1.471). CONCLUSIONS: The risk of post-CABG AKI was inversely and modestly related to the time between cardiac catheterization and CABG, with the highest incidence in those operated ≤ 1 day after cardiac catheterization despite their lower risk profile. Whether delaying elective CABG >24 hours of exposure to contrast agents (when feasible) has the potential for decreasing post-CABG AKI remains to be evaluated in future studies.

Modifiable risk factors associated with sudden cardiac arrest within hemodialysis clinics.

Sudden cardiac arrest is the most common cause of death among patients with end-stage kidney disease (ESKD) maintained on hemodialysis. Here we sought to identify dialysis-related factors associated with this increased risk in a case-control study encompassing 43,200 patients dialyzed in outpatient clinics of a large organization. Within this group, we compared the clinical and dialysis-specific data of 502 patients who experienced a sudden cardiac arrest with 1632 age- and dialysis-vintage-matched controls. There were 4.5 sudden cardiac arrest events per 100,000 dialysis treatments during the 3-year study period. These patients were significantly more likely to have been exposed to low potassium dialysate of less than 2 meq/l. These differences could not be explained by predialysis serum potassium levels. There was no evidence for a beneficial effect of low potassium dialysate even among those with higher predialysis serum potassium levels. Other factors strongly associated with sudden cardiac arrest by multivariable analysis included increased ultrafiltration volumes, exposure to low calcium dialysate, and predialysis serum creatinine levels. These relationships persisted after adjustment for covariates, but traditional risk factors such as history of coronary heart disease and congestive heart failure were not significantly influential. Hence, our study suggests that modifications of the hemodialysis prescription may improve the risk of sudden cardiac arrest in patients with ESKD.

Racial differences in long-term survival among patients with coronary artery disease.

BACKGROUND: Cardiovascular disease is the leading cause of death among blacks and whites in the United States. Despite this, there are insufficient data on the long-term prognosis of black patients with coronary artery disease (CAD) as well as the major clinical related determinants of outcome. METHODS: We studied 22,618 patients (3,314 black) having significant CAD findings at cardiac catheterization performed at Duke from January 1986 to December 2004 with follow-up through June 2006. Using Kaplan-Meier and Cox modeling, we compared unadjusted and adjusted long-term survival by patient race and gender (median follow-up 7.6 years, interquartile range 3.5-13.0) as well as identified major patient characteristics associated with survival. RESULTS: Blacks with CAD were younger; were more often female; had lower median household incomes; and had more hypertension, diabetes mellitus, and heart failure. The number of coronary vessels with significant disease was similar by race. At 15-year follow-up, black women had the lowest survival and white men had the highest (41.5% vs 45.8%, P < .0001). Blacks were less likely to receive initial therapy with coronary revascularization (odds ratio 0.66, 95% CI 0.60-0.72, P < .0001). After adjusting for baseline clinical and demographic characteristics and initial treatment selection, black race remained an independent predictor of lower survival (hazard ratio 2.54, 95% CI 1.60-4.04, P < .0001). CONCLUSIONS: Among patients with CAD, blacks have lower long-term survival compared with whites. The difference may be partially, but not fully, explained by differences in cardiovascular risk factors and 30-day revascularization rates.

Chronic kidney disease is associated with increased risk of sudden cardiac death among patients with coronary artery disease.

Sudden cardiac death is the most common cause of mortality among patients with end-stage kidney disease maintained on hemodialysis. To examine whether this increased risk is also seen with less advanced kidney disease, we studied the relationship between glomerular filtration rate and risk of sudden cardiac death in patients with moderate kidney disease and known coronary artery disease. This retrospective longitudinal study encompassed 19,440 consecutive patients who underwent cardiac catheterization at a single academic institution. There were 522 adjudicated sudden cardiac death events, yielding an overall rate of 4.6 events per 1000 patient years. This figure reflected rates of 3.8 events in 14,652 patients with estimated glomerular filtration rates (eGFR) > or =60 (stage 2 CKD or better) and 7.9 events in 4788 patients with glomerular filtration rates <60 (stage 3-5 CKD), all normalized to 1000 patient-years. After adjusting for differences in known cardiac risk factors and other covariates in a multivariate Cox proportional hazards model, the eGFR was independently associated with sudden cardiac death (hazard ratio (HR)=1.11 per 10 ml/min decline in the eGFR). Our analysis found that reductions in the eGFR in CKD stages 3-5 are associated with a progressive increase in risk of sudden cardiac death in patients with coronary artery disease. Additional studies are needed to better characterize the mechanisms by which reduced kidney function increases this risk.

Evaluation and management of thrombocytopenia and suspected heparin-induced thrombocytopenia in hospitalized patients: The Complications After Thrombocytopenia Caused by Heparin (CATCH) registry.

BACKGROUND: Thrombocytopenia and heparin-induced thrombocytopenia (HIT) are potentially devastating paradoxical side effects of heparin therapy. We explored the evaluation, management, and clinical consequences of thrombocytopenia occurring during heparin therapy in diverse clinical settings. METHODS: CATCH was a prospective observational study that enrolled 3,536 patients in 48 US hospitals. Data were collected on 3 strata: patients receiving any form of heparin for > or =96 hours (n = 2,420); cardiac care unit (CCU) patients treated with heparin who developed thrombocytopenia (n = 1,090); patients who had an HIT assay performed (n = 449). RESULTS: Thrombocytopenia occurred in 36.4% of patients in the prolonged heparin stratum and was associated with an increased risk of death or thromboembolic complication (OR 1.5, 95% CI 1.2-1.9). Among a subset of patients whose clinical presentation suggested they were at high risk for HIT, suspicion for HIT was uncommon (prolonged heparin stratum 19.8%, CCU stratum 37.6%) and often did not arise until > or =1 day after patients developed thrombocytopenia. Often patients were not evaluated for HIT until after they had had a thromboembolic complication (prolonged heparin stratum 43.8%, CCU stratum 61%). Even after HIT was suspected, patients often continued to receive heparin. Direct thrombin inhibitor use was infrequent (prolonged heparin stratum 29.4%, CCU stratum 35.6%). Among the few patients who underwent evaluation, HIT was confirmed in 46.7% of the prolonged heparin stratum and 31.4% of the CCU stratum. CONCLUSIONS: Thrombocytopenia is common among patients receiving heparin, and it is associated with substantial risk for catastrophic complications. Despite the high risk for HIT in this population, recognition, evaluation, and appropriate treatment are infrequent and delayed.

Incidence and prognostic significance of thrombocytopenia in patients treated with prolonged heparin therapy.

BACKGROUND: Despite widespread heparin use in clinical practice, the associated development of thrombocytopenia is an underrecognized and undertreated complication. METHODS: We analyzed data from consecutive hospitalized patients treated with heparin (unfractionated or low molecular weight) for 4 days or longer to determine the incidence, predictors, prognostic significance, and management of "thrombocytopenia," defined as a platelet count less than 150 x 10(9)/L, reduction in platelet count of 50% or more from the admission level, or both. RESULTS: We enrolled 2420 patients (median age, 65.2 years; 43.8% women) in 48 US hospitals. Thrombocytopenia occurred in 881 patients (36.4%; 95% confidence interval [CI], 34.5%-38.3%). Of those who developed thrombocytopenia, 5.1% died, compared with 1.6% of those without thrombocytopenia (odds ratio [OR], 3.4; 95% CI, 2.1-5.6; P< .001). Thrombocytopenia was also associated with greater risk of myocardial infarction (OR, 2.1; 95% CI, 1.5-2.8; P< .001) and congestive heart failure (OR, 1.3; 95% CI, 1.1-1.6; P= .01). After adjustment for important covariates, thrombocytopenia remained an independent predictor of thrombotic and hemorrhagic events. A relative reduction in platelet count of more than 70% was the strongest independent predictor of death (OR, 13.4; 95% CI, 6.5-27.6; P< .001), followed by a relative reduction in platelet count of 50% to 70%, worse Killip class, occurrence of thromboembolic complications, older age, and longer duration of heparin therapy. CONCLUSIONS: Thrombocytopenia occurs frequently after prolonged heparin therapy and is strongly associated with worse short-term clinical outcome. The relative reduction in platelet count is a powerful independent predictor of all-cause mortality in hospitalized patients.

Clinical characteristics associated with poor long-term survival among patients with diabetes mellitus undergoing saphenous vein graft interventions.

BACKGROUND: Limited data exist on the long-term outcomes among diabetic patients undergoing saphenous vein graft (SVG) interventions. Thus, the baseline clinical factors associated with long-term adverse events in these patients are less known. METHODS: Accordingly, we analyzed 1,160 consecutive patients (37.7% with diabetes) undergoing SVG interventions from the Duke Cardiovascular Disease Database (1990-2003). Cox proportional hazards modeling was used to identify predictors of long-term death in diabetic patients. The most significant model predictors were then used to construct a decision tree providing unadjusted Kaplan-Meier survival estimates at a median follow-up of 4 years. RESULTS: At median follow-up of 4 years, death (33.3% vs 18.1%, P < .0001; unadjusted hazard ratio 1.98, 95% CI 1.64-2.38) and death or myocardial infarction (49.6% vs 32.9%, unadjusted hazard ratio 1.71, 95% CI 1.462.00) were significantly higher in patients with diabetes mellitus compared with those without it. In patients with diabetes undergoing SVG interventions, a simple clinical decision algorithm, based on the most significant model predictors, demonstrated that 88% of patients without heart rate >80 beat/min, congestive heart failure, renal insufficiency, or hypertension survived after SVG intervention at median follow-up of 4 years. In contrast, none of the few patients with all these 4 factors survived at follow-up (100% mortality). CONCLUSIONS: Compared with patients without diabetes, diabetic patients undergoing SVG intervention have significantly worse long-term outcomes with one third dying at median follow-up of 4 years. We provide a simple decision tool that allows stepwise risk-stratification using baseline factors in diabetic patients undergoing SVG interventions and identify 4 risk factors associated with extremely poor long-term survival in this cohort.

The evolution of developmental regulatory pathways.

Evolutionary analysis of the content of developmental regulatory pathways has been advanced by the publication of pairs of complete genome sequences from representative taxonomic groups. Annotation of the fission yeast, rice, and mouse genomes confirms that most regulatory families are shared among eukaryotes but also shows that certain gene families have restricted distributions. Theoretical advances in the past few years include development of the theory of scale-free networks, which provides a new framework in which to consider the connectivity and evolution of regulatory systems, and introduction of algorithms that use comparative data to enhance detection of transcriptional regulatory motifs.

Evaluation of mechanical dyssynchrony and myocardial perfusion using phase analysis of gated SPECT imaging in patients with left ventricular dysfunction.

BACKGROUND: Using phase analysis of gated single photon emission computed tomography (SPECT) imaging, we examined the relation between myocardial perfusion, degree of electrical dyssynchrony, and degree of SPECT-derived mechanical dyssynchrony in patients with left ventricular (LV) dysfunction. METHODS AND RESULTS: We retrospectively examined 125 patients with LV dysfunction and ejection fraction of 35% or lower. Fourier analysis converts regional myocardial counts into a continuous thickening function, allowing resolution of phase of onset of myocardial thickening. The SD of LV phase distribution (phase SD) and histogram bandwidth describe LV phase dispersion as a measure of dyssynchrony. Heart failure (HF) patients with perfusion abnormalities have higher degrees of dyssynchrony measured by median phase SD (45.5 degrees vs 27.7 degrees, P < .0001) and bandwidth (117.0 degrees vs 73.0 degrees, P = .0006). HF patients with prolonged QRS durations have higher degrees of dyssynchrony measured by median phase SD (54.1 degrees vs 34.7 degrees, P < .0001) and bandwidth (136.5 degrees vs 99.0 degrees, P = .0005). Mild to moderate correlations exist between QRS duration and phase analysis indices of phase SD (r = 0.50) and bandwidth (r = 0.40). Mechanical dyssynchrony (phase SD >43 degrees) was 43.2%. CONCLUSIONS: HF patients with perfusion abnormalities or prolonged QRS durations have higher degrees of mechanical dyssynchrony. Gated SPECT myocardial perfusion imaging can quantify myocardial function, perfusion, and dyssynchrony and may help in evaluating patients for cardiac resynchronization therapy.

Repeatability and reproducibility of phase analysis of gated single-photon emission computed tomography myocardial perfusion imaging used to quantify cardiac dyssynchrony.

BACKGROUND: A novel method to quantify dyssynchrony has been developed using phase analysis of gated single-photon emission computed tomography perfusion imaging. We report on the effect of variability in image reconstruction on the phase analysis results (repeatability) and on the interobserver and intraobserver reproducibility of the technique. METHODS: Phase standard deviation (SD) and bandwidth are phase indices that quantify dyssynchrony. To evaluate repeatability, raw data sets were processed twice in 50 patients with left ventricular dysfunction and 50 normal controls. To determine the optimal processing method, two replicated phase analysis results were obtained using automated and manual base parameter placement. Reproducibility of the phase analysis was determined using the data from 20 patients. RESULTS: In normal controls, manual base parameter placement improves repeatability of the phase analysis as measured by the mean absolute difference between two reads for phase SD (12.0 degrees vs. 1.2 degrees , P<0.0001) and bandwidth (33.7 degrees vs. 3.6 degrees , P<0.0001). Repeatability is better for normal controls than for patients with left ventricular dysfunction for phase SD (1.2 degrees vs. 6.0 degrees , P<0.0001) and bandwidth (3.6 degrees vs. 26.5 degrees , P<0.0001). Reproducibility of the phase analysis is high as measured by the intraclass correlation coefficients for phase SD and bandwidth of 0.99 and 0.99 for the interobserver comparisons and 1.00 and 1.00 for the intraobserver comparisons. CONCLUSION: A novel method to quantify dyssynchrony has been developed using gated single-photon emission computed tomography perfusion imaging. Manual base parameter placement reduces the effect that variability in image reconstruction has on phase analysis. A high degree of reproducibility of phase analysis is observed.

Evaluation of combined cardiac positron emission tomography and coronary computed tomography angiography for the detection of coronary artery disease.

BACKGROUND: Coronary artery disease is a leading cause of morbidity and mortality. Multiple imaging modalities are used to screen for significant coronary artery disease. We report the concordance between coronary computed tomography angiography (CTA) and stress cardiac positron emission tomography (CPET) to detect significant coronary artery disease, the feasibility of combining CTA and CPET in one diagnostic test, and the ability of CTA and CPET to detect significant coronary artery disease by comparison with cardiac catheterization. METHODS: Forty patients were prospectively enrolled and imaged with a hybrid PET/CT scanner. Eighteen patients had cardiac catheterization data for comparison. Concordance of findings between diagnostic tests was assessed by examining overall percentage in agreement, area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values. RESULTS: The overall agreement between CTA and CPET for detecting significant coronary artery disease was 76.3% with a sensitivity and specificity of 91.7 and 69.2%, respectively. The overall agreement between CTA and cardiac catheterization for detecting significant coronary artery disease was 81.3% with a sensitivity and specificity of 81.8 and 80.0%, respectively. The overall agreement between CPET and cardiac catheterization for detecting significant coronary artery disease was 77.8% with a sensitivity and specificity of 76.9 and 80.0%, respectively. CONCLUSION: CTA and CPET can be performed in a single diagnostic test interval to simultaneously assess the extent of coronary artery disease and its hemodynamic significance. The sensitivity and specificity of CTA and CPET are similar to existing noninvasive screening tests.

Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial.

BACKGROUND: Urgency urinary incontinence (UUI) is a chronic condition for which sacral neuromodulation (SNM) (InterStim/Medtronic) and onabotulinumtoxinA (BTX) (BotoxA/Allergan) are utilized. These therapies have not been compared over extended time. OBJECTIVE: To compare UUI episodes (UUIE) over 24 mo following SNM or BTX. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label, randomized, extension trial (February 2012-July 2016) at nine US medical centers involving 386 women with ≥6 UUIE over 3 d inadequately managed by medications. Participants were clinical responders to treatment: ≥50% reduction in UUIEs after SNM placement or 1 mo post BTX. INTERVENTION: SNM (n=194) versus 200 U BTX (n=192). SNM reprogrammings occurred throughout the 24 mo. After 6 mo, two additional BTX injections were allowed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome: change in mean daily UUIE over 24 mo. SECONDARY OUTCOMES: no UUIE, ≥75% and ≥50% UUIE reduction; Overactive Bladder Questionnaire Short Form; Urinary Distress Inventory short form; Incontinence Impact Questionnaire; Patient Global Impression of Improvement; Overactive Bladder Satisfaction of Treatment Questionnaire; and adverse events (AEs). Primary analysis used a linear mixed model. RESULTS AND LIMITATIONS: Outcome data were available for 260/298 (87%) clinical responders. No difference in decreased mean UUIE was found over 24 mo (-3.88 vs -3.50 episodes/d,95% confidence interval [CI]=-0.14-0.89; p=0.15), with no differences in UUI resolution, ≥75% or ≥50% UUIE reduction. BTX group maintained higher satisfaction (mean difference=-9.14, 95% CI=-14.38--3.90; p<0.001), treatment endorsement (mean difference=-12.16, 95% CI=-17.7--6.63; p<0.001) through 24 mo. Other secondary measures did not differ. Recurrent urinary tract infections (UTIs) were higher after BTX (24% vs 10%; p<0.01), 6% required intermittent catheterization post second injection. SNM revision and removals occurred in 3% and 9% patients, respectively. CONCLUSIONS: Both treatments offered sustainable UUI improvement, and higher BTX dosing had low clean intermittent catheterization rates, but with UTI risk. SNM revision/removal rates were low due to standardized lead placement with strict treatment response definitions. PATIENT SUMMARY: We compared a large group of US women with severe urgency urinary incontinence (UUI) who received sacral neuromodulation (InterStim) or onabotulinumtoxinA (Botox A) therapy during a 2-yr period. We found that both therapies had similar success in reducing UUI symptoms, and adverse events were low. However, women in the BotoxA group had higher satisfaction and endorsement with their treatment, but with a higher chance of a urinary tract infection. We conclude that both therapies offer sustained reduction in daily incontinence over 2 yr.

Long-term outcomes of the symmetry vein graft anastomosis device: a matched case-control analysis.

BACKGROUND: The Symmetry Bypass Connector (St. Jude Medical) was developed to rapidly anastomose saphenous vein grafts to the aorta during coronary bypass surgery (CABG) without cross-clamping. Previous uncontrolled studies of this device observed vein graft closures at six months, possibly attributable to neointimal hyperplasia. METHODS AND RESULTS: To assess the long-term clinical outcomes of the Symmetry device, we performed a retrospective matched case-control analysis of patients who underwent CABG at Duke Medical Center between January 1, 2002 and December 31, 2003. In 121 patients, at least one proximal anastomosis used a Symmetry device. Traditional suture methods were used in 178 control patients, matched by age group, gender, use of cardiopulmonary bypass, and Hannan perioperative risk score. One-year outcomes were compared using the log-rank test and Cox proportional hazards regression models. Major adverse events were more frequent among cases compared with controls. By unadjusted Kaplan-Meier analysis for the composite end point of death, nonfatal myocardial infarction, repeat cardiac catheterization, or repeat CABG, there was a trend towards increased events in the Symmetry device group (P=0.053). No significant differences were detected for stroke, all cause mortality, or the combined end point of death or nonfatal myocardial infarction. CONCLUSIONS: Use of the Symmetry Bypass Connector was associated with increased risk for major adverse events at 1 year, suggestive of early graft closure. The potential reductions in operative stroke risk (from the elimination of aortic cross-clamping) must be weighed against the potential risk for later adverse events. These findings encourage close follow-up of patients who received this device.

Impact of internal mammary artery conduit on long-term outcomes after percutaneous intervention of saphenous vein graft.

BACKGROUND: The influence of an internal mammary artery (IMA) graft on long-term outcomes after percutaneous saphenous vein graft (SVG) intervention is currently unknown. METHODS AND RESULTS: To examine the impact of IMA on outcomes in patients undergoing SVG interventions, we analyzed 2119 patients from the Duke Cardiovascular Disease Database (1986-2003) with prior coronary artery bypass surgery undergoing cardiac catheterization who had at least 1 SVG graft. Patients were categorized into 4 groups: group I, SVG intervention and patent IMA; group II, no SVG intervention and patent IMA; group III, SVG intervention without patent IMA; and group IV, no SVG intervention without patent IMA. At a median follow-up of 4.8 years (interquartile range, 2.1 to 8.8 years), adjusted survival rates in groups I, II, III, and IV were 72.8%, 72.3%, 64.5%, and 58.9%, respectively. Multivariate Cox proportional hazards modeling showed similar survival for groups I and II (P=0.63) and for groups III and IV (P=0.33). The presence of IMA graft was related to lower long-term mortality (adjusted hazard ratio [HR], 0.69; 95% CI, 0.58 to 0.82), whereas SVG intervention was not associated with long-term mortality (adjusted HR, 0.94; 95% CI, 0.81 to 1.10). In contrast, the adjusted event-free rates for nonfatal myocardial infarction were lower in the SVG intervention groups (groups I and III) than in the non-SVG intervention groups (groups II and IV) (HR for SVG intervention versus no SVG intervention, 3.19; 95% CI, 2.18 to 4.66), with the presence of patent IMA conferring no significant benefit on this outcome (HR, 1.37; 95% CI, 0.91 to 2.08). CONCLUSIONS: In patients undergoing SVG interventions, survival, but not nonfatal myocardial infarction, is favorably influenced by the presence of patent IMA. In contrast, SVG intervention had no measurable survival benefit but was associated with an increased risk of nonfatal myocardial infarction.

Clinical and angiographic correlates of short- and long-term mortality in patients undergoing coronary artery bypass grafting.

Differences in the clinical and angiographic factors associated with short- and long-term outcomes in patients undergoing coronary artery bypass grafting (CABG) are less known. Accordingly, differences were examined in clinical and angiographic correlates of short- and long-term mortality after CABG in 8,229 patients undergoing initial CABG enrolled in the Duke Cardiovascular Disease Database (1995 to 2002). Logistic regression and Cox proportional hazard modeling were performed to determine independent correlates of 30-day and long-term mortality. Death occurred in 2.4% at 30 days and 17.6% beyond 30 days at a median follow-up of 6 years in patients who underwent CABG. Multivariable models identified older age, lower left ventricular ejection fraction, lower or higher body mass index, cerebrovascular disease, lack of internal mammary artery use, and lower cholesterol to be associated with increased risk of both events. Although hemodynamic status (preoperative myocardial infarction, New York Heart Association class, and cardiogenic shock), female gender, and minority race were associated with 30-day death; co-morbid conditions (serum creatinine, chronic lung disease, diabetes, previous heart failure, peripheral vascular disease, and left main disease) were associated with increased long-term (beyond 30 days) death (c indexes 0.76 and 0.79 for the short- and long-term mortality models, respectively). In conclusion, our study suggested that correlates of acute and long-term death were different in patients undergoing CABG. These differences should be kept in context when counseling patients undergoing CABG and may help facilitate targeted strategies to improve short- and long-term mortality risks after CABG.

Clinical results of a novel wide beam reconstruction method for shortening scan time of Tc-99m cardiac SPECT perfusion studies.

BACKGROUND: Newly developed reconstruction algorithms enable the acquisition of images at half of the scan time while maintaining image quality. The purpose of this investigation was to evaluate a novel wide beam reconstruction (WBR) method developed by UltraSPECT for decreasing scan times and to compare it with filtered backprojection (FBP), which is the technique routinely used. METHODS AND RESULTS: Phantom and clinical studies were performed. Hot and cold sphere and cardiac phantom acquisitions were reconstructed via WBR, FBP, and ordered-subsets expectation maximization. Fifty patients were prospectively studied by use of both a standard and a short protocol. The short protocol was performed first on 29 of 50 patients via 8-frame gated technetium 99m stress single photon emission computed tomography and low-energy high-resolution collimators. Stress Tc-99m studies (30-45 mCi) were scanned for 20 seconds per frame. For the short protocol, all parameters remained constant except for the time per frame, which was reduced by 50% on Tc-99m studies. All resting Tc-99m scans (36/50 patients) were processed with FBP for the standard full-scan time studies and with WBR for the short scan studies. The images were interpreted by use of a 17-segment model and 5-degree severity score, and the perfusion and functional variables were determined. Distributions including mean, median, and interquartile ranges were examined for all variables. The differences (FBP - WBR) were computed for all variables and were examined by use of nonparametric signed rank tests to determine whether the median difference was 0. The absolute value of the difference was also examined. Spearman rank-order correlation, a nonparametric measure of association, was used for the 2 methods to determine significant correlations between variables. The hot and cold sphere phantom studies demonstrated that WBR had improved contrast recovery and slightly better background uniformity than did the ordered-subsets expectation maximization. The cardiac phantom studies performed with attenuating medium and background activity showed that the half-scan time images processed with WBR had better contrast recovery and background uniformity than did the full-scan time FBP reconstruction. In the clinical studies, highly significant correlations were observed between WBR and FBP for functional as well as perfusion variables (P < .0001). The summed stress score, summed rest scores, and summed difference score were not statistically different for FBP and WBR (P > .05). Left ventricular volumes had a high correlation coefficient but were significantly larger with FBP than with WBR. CONCLUSION: Our study results suggest that cardiac single photon emission computed tomography perfusion studies may be performed with the WBR algorithm using half of the scan time without compromising qualitative or quantitative imaging results.