Sreekanth Vemulapalli

Clinical Outcomes at 1 Year Following Transcatheter Aortic Valve Replacement

IMPORTANCE Introducing new medical devices into routine practice raises concerns because patients and outcomes may differ from those in randomized trials. OBJECTIVE To update the previous report of 30-day outcomes and present 1-year outcomes following transcatheter aortic valve replacement (TAVR) in the United States. DESIGN, SETTING, AND PARTICIPANTS Data from the Society of Thoracic Surgeons/American College of Cardiology (STS/ACC) Transcatheter Valve Therapies Registry were linked with patient-specific Centers for Medicare & Medicaid Services (CMS) administrative claims data. At 299 US hospitals, 12 182 patients linked with CMS data underwent TAVR procedures performed from November 2011 through June 30, 2013, and the end of the follow-up period was June 30, 2014. EXPOSURE Transcatheter aortic valve replacement. MAIN OUTCOMES AND MEASURES One-year outcomes including mortality, stroke, and rehospitalization were evaluated using multivariate modeling. RESULTS The median age of patients was 84 years and 52% were women, with a median STS Predicted Risk of Operative Mortality (STS PROM) score of 7.1%. Following the TAVR procedure, 59.8% were discharged to home and the 30-day mortality was 7.0% (95% CI, 6.5%-7.4%) (n = 847 deaths). In the first year after TAVR, patients were alive and out of the hospital for a median of 353 days (interquartile range, 312-359 days); 24.4% (n = 2074) of survivors were rehospitalized once and 12.5% (n = 1525) were rehospitalized twice. By 1 year, the overall mortality rate was 23.7% (95% CI, 22.8%-24.5%) (n = 2450 deaths), the stroke rate was 4.1% (95% CI, 3.7%-4.5%) (n = 455 stroke events), and the rate of the composite outcome of mortality and stroke was 26.0% (25.1%-26.8%) (n = 2719 events). Characteristics significantly associated with 1-year mortality included advanced age (hazard ratio [HR] for ≥95 vs <75 years, 1.61 [95% CI, 1.24-2.09]; HR for 85-94 years vs <75 years, 1.35 [95% CI, 1.18-1.55]; and HR for 75-84 years vs <75 years, 1.23 [95% CI, 1.08-1.41]), male sex (HR, 1.21; 95% CI, 1.12-1.31), end-stage renal disease (HR, 1.66; 95% CI, 1.41-1.95), severe chronic obstructive pulmonary disease (HR, 1.39; 95% CI, 1.25-1.55), nontransfemoral access (HR, 1.37; 95% CI, 1.27-1.48), STS PROM score greater than 15% vs less than 8% (HR, 1.82; 95% CI, 1.60-2.06), and preoperative atrial fibrillation/flutter (HR, 1.37; 95% CI, 1.27-1.48). Compared with men, women had a higher risk of stroke (HR, 1.40; 95% CI, 1.15-1.71). CONCLUSIONS AND RELEVANCE Among patients undergoing TAVR in US clinical practice, at 1-year follow-up, overall mortality was 23.7%, the stroke rate was 4.1%, and the rate of the composite outcome of death and stroke was 26.0%. These findings should be helpful in discussions with patients undergoing TAVR.

Outer Membrane Vesicle Production by Escherichia coli Is Independent of Membrane Instability

It has been long noted that gram-negative bacteria produce outer membrane vesicles, and recent data demonstrate that vesicles released by pathogenic strains can transmit virulence factors to host cells. However, the mechanism of vesicle release has remained undetermined. This genetic study addresses whether these structures are merely a result of membrane instability or are formed by a more directed process. To elucidate the regulatory mechanisms and physiological basis of vesiculation, we conducted a screen in Escherichia coli to identify gene disruptions that caused vesicle over- or underproduction. Only a few low-vesiculation mutants and no null mutants were recovered, suggesting that vesiculation may be a fundamental characteristic of gram-negative bacterial growth. Gene disruptions were identified that caused differences in vesicle production ranging from a 5-fold decrease to a 200-fold increase relative to wild-type levels. These disruptions included loci governing outer membrane components and peptidoglycan synthesis as well as the sigma(E) cell envelope stress response. Mutations causing vesicle overproduction did not result in upregulation of the ompC gene encoding a major outer membrane protein. Detergent sensitivity, leakiness, and growth characteristics of the novel vesiculation mutant strains did not correlate with vesiculation levels, demonstrating that vesicle production is not predictive of envelope instability.

Annual Outcomes With Transcatheter Valve Therapy: From the STS/ACC TVT Registry.

BACKGROUND The Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry has been a joint initiative of the STS and the ACC in concert with multiple stakeholders. The TVT Registry has important information regarding patient selection, delivery of care, science, education, and research in the field of structural valvular heart disease. OBJECTIVES This report provides an overview on current U.S. TVT practice and trends. The emphasis is on demographics, in-hospital procedural characteristics, and outcomes of patients having transcatheter aortic valve replacement (TAVR) performed at 348 U.S. centers. METHODS The TVT Registry captured 26,414 TAVR procedures as of December 31, 2014. Temporal trends between 2012 and 2013 versus 2014 were compared. RESULTS Comparison of the 2 time periods reveals that TAVR patients remain elderly (mean age 82 years), with multiple comorbidities, reflected by a high mean STS predicted risk of mortality (STS PROM) for surgical valve replacement (8.34%), were highly symptomatic (New York Heart Association functional class III/IV in 82.5%), frail (slow 5-m walk test in 81.6%), and have poor self-reported health status (median baseline Kansas City Cardiomyopathy Questionnaire score of 39.1). Procedure performance is changing, with an increased use of moderate sedation (from 1.6% to 5.1%) and increase in femoral access using percutaneous techniques (66.8% in 2014). Vascular complication rates are decreasing (from 5.6% to 4.2%), whereas site-reported stroke rates remain stable at 2.2%. CONCLUSIONS The TVT Registry provides important information on characteristics and outcomes of TAVR in contemporary U.S. clinical practice. It can be used to identify trends in practice and opportunities for quality improvement.

Initial Experience With Commercial Transcatheter Mitral Valve Repair in the United States.

BACKGROUND Transcatheter mitral valve (MV) repair with the MitraClip received approval in 2013 for the treatment of prohibitive-risk patients with primary mitral regurgitation (MR). OBJECTIVES The aim of this study was to report the initial U.S. commercial experience with transcatheter MV repair. METHODS Data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry on patients commercially treated with this percutaneous mitral valve repair device were analyzed. RESULTS Of 564 patients (56% men, median age 83 years), severe symptoms were present in 473 (86.0%). The median Society of Thoracic Surgeons Predicted Risk of Mortality scores for MV repair and replacement were 7.9% (interquartile range: 4.7% to 12.2%) and 10.0% (interquartile range: 6.3% to 14.5%), respectively. Frailty was noted in 323 patients (57.3%). Transcatheter MV repair was performed for degenerative disease, present in 90.8% of patients. Overall, MR was reduced to grade ≤2 in 93.0%. In-hospital mortality was 2.3%; 30-day mortality was 5.8%. Other 30-day events were stroke (1.8%), bleeding (2.6%), and device-related complications (1.4%). The median length of stay was 3 days (interquartile range: 1 to 6 days), with 84.0% patients discharged home. Overall, procedure success occurred in 90.6%. Variables associated with reduction in MR were end-diastolic dimension, MR severity, clip location, and case volume. CONCLUSIONS In this study of the initial commercial U.S. experience, it was found that procedural success was achieved in approximately 91% of patients, and the majority of patients were discharged home with moderate or less MR. These data support the effectiveness of this therapy in appropriately selected high-risk patients in a commercial setting. Further study is required to determine the long-term impact of transcatheter MV repair in this patient population.

Molecular imaging of small animals with a triple-head SPECT system using pinhole collimation

Pinhole collimation yields high sensitivity when the distance from the object to the aperture is small, as in the case of imaging small animals. Fine-resolution images may be obtained when the magnification is large since this mitigates the effect of detector resolution. Large magnifications in pinhole single-photon emission computed tomography (SPECT) may be obtained by using a collimator whose focal length is many times the radius of rotation. This may be achieved without truncation if the gamma camera is large. We describe a commercially available clinical scanner mated with pinhole collimation and an external linear stage. The pinhole collimation gives high magnification. The linear stage allows for helical pinhole SPECT. We have used the system to image radiolabeled molecules in phantoms and small animals.

High mortality risks after major lower extremity amputation in Medicare patients with peripheral artery disease

BACKGROUND Little is known regarding the contemporary outcomes of older patients with peripheral artery disease (PAD) undergoing major lower extremity (LE) amputation in the United States. We sought to characterize clinical outcomes and factors associated with outcomes after LE amputation in patients with PAD. METHODS Using data from the Centers for Medicare and Medicaid Services from January 1, 2000, to December 31, 2008, we examined the national patterns of mortality after major LE amputation among patients 65 years or older with PAD. Cox proportional hazards models were used to investigate the association between clinical variables, comorbid conditions, year of index amputation, geographic variation, and major LE amputation. RESULTS Among 186,338 older patients with identified PAD who underwent major LE amputation, the mortality rate was 13.5% at 30 days, 48.3% at 1 year, and 70.9% at 3 years. Age per 5-year increase (hazard ratio [HR] 1.29, 95% CI 1.29-1.29), history of heart failure (HR 1.71, 95% CI 1.71-1.72), renal disease (HR 1.84. 95% CI 1.83-1.85), cancer (HR 1.71, 95% CI 1.70-1.72), and chronic obstructive pulmonary disease (HR 1.33, 95% CI, 1.32-1.33) were all independently associated with death after major LE amputation. Subjects who underwent above knee amputation had a statistically higher hazard of death when compared with subjects who underwent LE amputation at more distal locations (HR with above the knee amputation 1.31, 95% CI 1.25-1.36). CONCLUSIONS Older patients with PAD undergoing major LE amputation still face a slightly high mortality risk, with almost half of all patients with PAD dying within a year of major LE amputation.

Comparative effectiveness of endovascular and surgical revascularization for patients with peripheral artery disease and critical limb ischemia

BACKGROUND For patients with critical limb ischemia (CLI), the optimal treatment to enhance limb preservation, prevent death, and improve functional status is unknown. We performed a systematic review and meta-analysis to assess the comparative effectiveness of endovascular revascularization and surgical revascularization in patients with CLI. METHODS We systematically searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1995 to August 2012. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects, with endovascular treatment as the control group. RESULTS We identified a total of 23 studies, including 1 randomized controlled trial, which reported no difference in amputation-free survival at 3 years (odds ratio [OR] 1.22, 95% CI 0.84-1.77) and all-cause mortality (OR 1.07, 0.73-1.56) between the 2 treatments. Meta-analysis of the observational studies showed a statistically nonsignificant reduction in all-cause mortality at 6 months (11 studies, OR 0.85, 0.57-1.27) and amputation-free survival at 1 year (2 studies, OR 0.76, 0.48-1.21) in patients treated with endovascular revascularization. There was no difference in overall death, amputation, or amputation-free survival at ≥2 years. CONCLUSIONS The currently available literature suggests that there is no difference in clinical outcomes for patients with CLI treated with endovascular or surgical revascularization. There is a paucity of high-quality data available to guide clinical decision making, especially as it pertains to patient subgroups or anatomical considerations.

Gait Speed Predicts 30-Day Mortality After Transcatheter Aortic Valve Replacement Results From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry

Background— Surgical risk scores do not include frailty assessments (eg, gait speed), which are of particular importance for patients with severe aortic stenosis considering transcatheter aortic valve replacement. Methods and Results— We assessed the association of 5-m gait speed with outcomes in a cohort of 8039 patients who underwent transcatheter aortic valve replacement (November 2011–June 2014) and were included in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for Society of Thoracic Surgeons–predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The overall median gait speed was 0.63 m/s (25th–75th percentile, 0.47–0.79 m/s), with the slowest walkers (<0.5 m/s) constituting 28%, slow walkers (0.5–0.83 m/s) making up 48%, and normal walkers (>0.83 m/s) constituting 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively (P<0.001). Each 0.2-m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio, 1.11; 95% confidence interval, 1.01–1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio, 1.35; 95% confidence interval, 1.01–1.80), significantly longer hospital stays, and a lower probability of being discharged to home. Conclusions— Gait speed is independently associated with 30-day mortality after transcatheter aortic valve replacement. Identification of frail patients with the slowest gait speeds facilitates preprocedural evaluation and anticipation of a higher level of postprocedural care. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737528.

Transapical and Transaortic Transcatheter Aortic Valve Replacement in the United States

BACKGROUND When transcatheter aortic valve replacement (TAVR) cannot be carried out through transfemoral access, alternative access TAVR is indicated. The purpose of this study was to explore inhospital and 1-year outcomes of patients undergoing alternative access TAVR through the transapical (TA) or transaortic (TAo) techniques in the United States. METHODS Clinical records of 4,953 patients undergoing TA (n = 4,085) or TAo (n = 868) TAVR from 2011 to 2014 in The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry were linked to Centers for Medicare and Medicaid Services hospital claims. Inhospital and 1-year clinical outcomes were stratified by operative risk; and the risk-adjusted association between access route and mortality, stroke, and heart failure repeat hospitalization was explored. RESULTS Mean age for all patients was 82.8 ± 6.8 years. The median STS predicted risk of mortality was significantly higher among patients undergoing TAo (8.8 versus 7.4, p < 0.001). When compared with TA, TAo was associated with an increased risk of unadjusted 30-day mortality (10.3% versus 8.8%) and 1-year mortality (30.3% versus 25.6%, p = 0.006). There were no significant differences between TAo and TA for inhospital stroke rate (2.2%), major vascular complications (0.3%), and 1-year heart failure rehospitalizations (15.7%). Examination of high-risk and inoperable subgroups showed that 1-year mortality was significantly higher for TAo patients classified as inoperable (p = 0.012). CONCLUSIONS Patients undergoing TAo TAVR are older, more likely female, and have significantly higher STS predicted risk of mortality scores than patients operated on by TA access. There were no risk-adjusted differences between TA and TAo access in mortality, stroke, or readmission rates as long as 1 year after TAVR.

Conscious Sedation Versus General Anesthesia for Transcatheter Aortic Valve Replacement: Insights from the National Cardiovascular Data Registry Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry

Background: Conscious sedation is used during transcatheter aortic valve replacement (TAVR) with limited evidence as to the safety and efficacy of this practice. Methods: The National Cardiovascular Data Registry Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was used to characterize the anesthesia choice and clinical outcomes of all US patients undergoing elective percutaneous transfemoral TAVR between April 1, 2014, and June 30, 2015. Raw and inverse probability of treatment-weighted analyses were performed to compare patients undergoing TAVR with general anesthesia with patients undergoing TAVR with conscious sedation on an intention-to-treat basis for the primary outcome of in-hospital mortality, and secondary outcomes including 30-day mortality, in-hospital and 30-day death/stroke, procedural success, intensive care unit and hospital length-of-stay, and rates of discharge to home. Post hoc falsification end point analyses were performed to evaluate for residual confounding. Results: Conscious sedation was used in 1737/10 997 (15.8%) cases with a significant trend of increasing usage over the time period studied (P for trend<0.001). In raw analyses, intraprocedural success with conscious sedation and general anesthesia was similar (98.2% versus 98.5%, P=0.31). The conscious sedation group was less likely to experience in-hospital (1.6% versus 2.5%, P=0.03) and 30-day death (2.9% versus 4.1%, P=0.03). Conversion from conscious sedation to general anesthesia was noted in 102 of 1737 (5.9%) of conscious sedation cases. After inverse probability of treatment-weighted adjustment for 51 covariates, conscious sedation was associated with lower procedural success (97.9% versus 98.6%, P<0.001) and a reduced rate of mortality at the in-hospital (1.5% versus 2.4%, P<0.001) and 30-day (2.3% versus 4.0%, P<0.001) time points. Conscious sedation was associated with reductions in procedural inotrope requirement, intensive care unit and hospital length of stay (6.0 versus 6.5 days, P<0.001), and combined 30-day death/stroke rates (4.8% versus 6.4%, P<0.001). Falsification end point analyses of vascular complications, bleeding, and new pacemaker/defibrillator implantation demonstrated no significant differences between groups after adjustment. Conclusions: In US practice, conscious sedation is associated with briefer length of stay and lower in-hospital and 30-day mortality in comparison with TAVR with general anesthesia in both unadjusted and adjusted analyses. These results suggest the safety of conscious sedation in this population, although comparative effectiveness analyses using observational data cannot definitively establish the superiority of one technique over another.Background —Conscious sedation is used during transcatheter aortic valve replacement (TAVR) with limited evidence as to the safety and efficacy of this practice. Methods —The NCDR STS/ACC TVT Registry was used to characterize the anesthesia choice and clinical outcomes of all U.S. patients undergoing elective percutaneous transfemoral TAVR between April 1, 2014 and June 30, 2015. Raw and inverse probability of treatment weighted (IPTW) analyses were performed to compare general anesthesia patients with conscious sedation patients on an intention-to-treat basis for the primary outcome of in-hospital mortality, and secondary outcomes including 30-day mortality, in-hospital and 30-day death/stroke, procedural success, ICU and hospital length-of-stay, and rates of discharge to home. Post-hoc falsification endpoint analyses were performed to evaluate for residual confounding. Results —Conscious sedation was used in 1,737/10,997 (15.8%) cases with a significant trend of increasing usage over the time period studied (p for trend Conclusions —In U.S. practice, conscious sedation is associated with briefer length of stay and lower in-hospital and 30-day mortality compared to TAVR with general anesthesia in both unadjusted and adjusted analyses. These results suggest the safety of conscious sedation in this population, though comparative effectiveness analyses using observational data cannot definitively establish the superiority of one technique over another.