Publications by authors named "John A House"

53 Publications

Associations Between Wildfire-Related PM and Intensive Care Unit Admissions in the United States, 2006-2015.

Geohealth 2021 May 1;5(5):e2021GH000385. Epub 2021 May 1.

Division of Biostatistics and Bioinformatics and Department of Immunology and Genomic Medicine National Jewish Health Denver CO USA.

Wildfire smoke is a growing public health concern in the United States. Numerous studies have documented associations between ambient smoke exposure and severe patient outcomes for single-fire seasons or limited geographic regions. However, there are few national-scale health studies of wildfire smoke in the United States, few studies investigating Intensive Care Unit (ICU) admissions as an outcome, and few specifically framed around hospital operations. This study retrospectively examined the associations between ambient wildfire-related PM at a hospital ZIP code with total hospital ICU admissions using a national-scale hospitalization data set. Wildfire smoke was characterized using a combination of kriged PM monitor observations and satellite-derived plume polygons from National Oceanic and Atmospheric Administration's Hazard Mapping System. ICU admissions data were acquired from Premier, Inc. and encompass 15%-20% of all U.S. ICU admissions during the study period. Associations were estimated using a distributed-lag conditional Poisson model under a time-stratified case-crossover design. We found that a 10 μg/m increase in daily wildfire PM was associated with a 2.7% (95% CI: 1.3, 4.1;  = 0.00018) increase in ICU admissions 5 days later. Under stratification, positive associations were found among patients aged 0-20 and 60+, patients living in the Midwest Census Region, patients admitted in the years 2013-2015, and non-Black patients, though other results were mixed. Following a simulated severe 7-day 120 μg/m smoke event, our results predict ICU bed utilization peaking at 131% (95% CI: 43, 239; < 10) over baseline. Our work suggests that hospitals may need to preposition vital critical care resources when severe smoke events are forecast.
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http://dx.doi.org/10.1029/2021GH000385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095362PMC
May 2021

Evaluation of a Clinical Platform to Promote Chronic Disease Management.

Popul Health Manag 2021 08 7;24(4):470-477. Epub 2020 Dec 7.

Premier Applied Sciences, Premier, Inc., Charlotte, North Carolina, USA.

Self-reported data suggest American adults with multiple chronic conditions account for 25.7% to 60% of the population. Despite emphasis on information technology to improve quality in health care, data addressing outcomes of clinically focused, provider-oriented dashboards are limited. To explore integrating performance platforms into clinical care, the authors designed a platform-based intervention to address 2 prevalent chronic conditions with significant long-term burden. This study used a performance platform to enhance clinicians' management of patients with diabetes and osteoporosis. Descriptive statistics were used to summarize patients' surveys and quality metrics, and to analyze clinicians' knowledge, attitudes, and beliefs in the pre and post time frames. The frequency of screening for osteoporosis in women improved post intervention (40% vs. 44%,  < 0.0001), whereas other quality metrics did not. Clinician respondents were primarily physicians (82%), white (73%), internal medicine specialists (58%), with an average of 18 years' experience, and nearly equally male and female. Their percent of correctly answered knowledge questions increased slightly in the postintervention phase for osteoporosis and hypoglycemia (0.53 and 1.74, respectively); however, results were not statistically significant ( > 0.4). Post intervention, clinicians reported that their attitudes and beliefs regarding disease management had changed in the past 6 months in a positive direction. Although few outcomes studied changed over time, results suggest that performance platforms may have a role to play in managing chronic conditions. However, their efficacy must continue to be evaluated in order to improve understanding of optimal approaches to integrating technology into patient care.
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http://dx.doi.org/10.1089/pop.2020.0205DOI Listing
August 2021

Improving Care Pathways for Acute Coronary Syndrome: Patients Undergoing Percutaneous Coronary Intervention.

Am J Cardiol 2020 02 26;125(3):354-361. Epub 2019 Oct 26.

University of Colorado, Anschutz Medical Campus, Aurora, Colorado.

Acute coronary syndrome (ACS) admissions are common and costly. The association between comprehensive ACS care pathways, outcomes, and costs are lacking. From 434,172 low-risk, uncomplicated ACS patients eligible for early discharge (STEMI 35%, UA/NSTEMI 65%) from the Premier database, we identified ACS care pathways, by stratifying low-risk, uncomplicated STEMI and UA/NSTEMI patients by access site for PCI (trans-radial intervention [TRI] vs transfemoral intervention [TFI]) and by length of stay (LOS). Associations with costs and outcomes (death, bleeding, acute kidney injury, and myocardial infarction at 1-year) were tested using hierarchical, mixed-effects regression, and projections of cost savings with change in care pathways were obtained using modeling. In low-risk uncomplicated STEMI patients, compared with TFI and LOS ≥3 days, a strategy of TRI with LOS <3 days and TFI with LOS <3 days were associated with cost savings of $6,206 and $4,802, respectively. Corresponding cost savings for UA/NSTEMI patients were $7,475 and $6,169, respectively. These care-pathways did not show an excess risk of adverse outcomes. We estimated that >$300 million could be saved if prevalence of the TRI with LOS <3 days and TFI with LOS <3 days strategies are modestly increased to 20% and 70%, respectively. In conclusion, we demonstrate the potential opportunity of cost savings by repositioning ACS care pathways in low-risk and uncomplicated ACS patients, toward transradial access and a shorter LOS without an increased risk of adverse outcomes.
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http://dx.doi.org/10.1016/j.amjcard.2019.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809633PMC
February 2020

The Evolving Landscape of Impella Use in the United States Among Patients Undergoing Percutaneous Coronary Intervention With Mechanical Circulatory Support.

Circulation 2020 01 17;141(4):273-284. Epub 2019 Nov 17.

The Duke Clinical Research Institute, Durham, NC (S.V.R.).

Background: Impella was approved for mechanical circulatory support (MCS) in 2008, but large-scale, real-world data on its use are lacking. Our objective was to describe trends and variations in Impella use, clinical outcomes, and costs across US hospitals in patients undergoing percutaneous coronary intervention (PCI) treated with MCS (Impella or intra-aortic balloon pump).

Methods: From the Premier Healthcare Database, we analyzed 48 306 patients undergoing PCI with MCS at 432 hospitals between January 2004 and December 2016. Association analyses were performed at 3 levels: time period, hospital, and patient. Hierarchical models with propensity adjustment were used for association analyses. We examined trends and variations in the proportion of Impella use, and associated clinical outcomes (in-hospital mortality, bleeding requiring transfusion, acute kidney injury, stroke, length of stay, and hospital costs).

Results: Among patients undergoing PCI treated with MCS, 4782 (9.9%) received Impella; its use increased over time, reaching 31.9% of MCS in 2016. There was wide variation in Impella use across hospitals (>5-fold variation). Specifically, among patients receiving Impella, there was a wide variation in outcomes of bleeding (>2.5-fold variation), and death, acute kidney injury, and stroke (all ≈1.5-fold variation). Adverse outcomes and costs were higher in the Impella era (years 2008-2016) versus the pre-Impella era (years 2004-2007). Hospitals with higher Impella use had higher rates of adverse outcomes and costs. After adjustment for the propensity score, and accounting for clustering of patients by hospitals, Impella use was associated with death: odds ratio, 1.24 (95% CI, 1.13-1.36); bleeding: odds ratio, 1.10 (95% CI, 1.00-1.21); and stroke: odds ratio, 1.34 (95% CI, 1.18-1.53), although a similar, nonsignificant result was observed for acute kidney injury: odds ratio, 1.08 (95% CI, 1.00-1.17).

Conclusions: Impella use is rapidly increasing among patients undergoing PCI treated with MCS, with marked variability in its use and associated outcomes. Although unmeasured confounding cannot be ruled out, when analyzed by time periods, or at the hospital level or the patient level, Impella use was associated with higher rates of adverse events and costs. More data are needed to define the appropriate role of MCS in patients undergoing PCI.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044007DOI Listing
January 2020

Incremental Cost of Acute Kidney Injury after Percutaneous Coronary Intervention in the United States.

Am J Cardiol 2020 01 10;125(1):29-33. Epub 2019 Oct 10.

University of Colorado Anschutz Medical Campus Aurora, CO.

Contrast-induced acute kidney injury (AKI) is a common and severe complication of percutaneous coronary intervention (PCI). Despite its substantial burden, contemporary data on the incremental costs of AKI are lacking. We designed this large, nationally representative study to examine: (1) the independent, incremental costs associated with AKI after PCI and (2) to identify the departmental components of cost contributing to the incremental costs associated with AKI. In this observational cross-sectional study from the Premier database, we analyzed 1,443,297 PCI patients at 518 US hospitals from 1/2006 to 12/2015. Incremental cost of AKI from a hospital perspective obtained by a microcosting approach, was estimated using mixed-effects, multivariable linear regression with hospitals as random effects. Costs were inflation-corrected to 2016 US$. AKI occurred in 82,683 (5.73%) of the PCI patients. Those with AKI had higher hospitalization cost than those without ($38,869, SD 42,583 vs $17,167 SD 13,994, p <0.001). After adjustment, the incremental cost associated with an AKI was $9,448 (95% confidence interval $9,338 to $9,558, p <0.001). AKI was also independently associated with an incremental length of stay of 3.6 days (p <0.001). Room and board costs were the largest driver of AKI costs ($4,841). Extrapolated to the United States, our findings imply an annual AKI cost burden of 411.3 million US$. In conclusion, in this national study of PCI patients, AKI was common and independently associated with ∼$10,000 incremental costs, implying a substantial burden of AKI costs in US hospitals. Successful efforts to prevent AKI in patients who underwent PCI could result in meaningful cost savings.
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http://dx.doi.org/10.1016/j.amjcard.2019.09.042DOI Listing
January 2020

Cytomegalovirus infection and associated hospitalization and costs among individuals undergoing allogeneic hematopoietic stem cell transplant.

Curr Med Res Opin 2020 01 23;36(1):43-50. Epub 2019 Sep 23.

Merck & Co., Inc, Kenilworth, NJ, USA.

This study utilized a large, national US database to explore the impact of Cytomegalovirus (CMV) infection on hospital services utilization and costs during the first 100 days following allogeneic hematopoietic stem cell transplant (allo-HSCT). This retrospective, observational cohort study used data from the Premier Healthcare database to identify patients undergoing their first (index) allo-HSCT procedure between 1 January 2006 and 31 March 2015. Three subgroups were analyzed according to CMV-related readmissions during the 100-day follow-up (0, 1, or 2+ readmissions) to compare healthcare utilization and costs. A total of 1610 patients (mean age, 50.5 years; 56.9% male) from 52 US hospitals met the inclusion criteria. During follow-up, 212 (13.2%) patients had 1 ( = 161; 10.0%) or 2+ ( = 51; 3.2%) CMV-related readmissions. The mean ± SD number of all follow-up encounters (inpatient admissions and hospital-based outpatient visits) was similar for the no CMV (3.9 ± 3.9), 1 CMV (3.7 ± 3.9), and 2+ CMV (4.5 ± 3.8) readmission groups ( = .439). Mean total costs of hospital-based healthcare encounters (inpatient admissions and hospital-based outpatient visits) during follow-up were significantly greater in patients who had a CMV readmission ($111,729 [1 CMV readmission]; $184,021 [2+ CMV readmissions]) compared to those without a CMV readmission ($46,064;  < .001]. 100-day follow-up mortality was higher in the CMV vs. non-CMV readmission groups (30.2 vs. 8.2%;  < .001). This large, national database study revealed significantly higher healthcare utilization and costs, as well as mortality, among patients with CMV-related re-hospitalization during the first 100 days post-transplant as compared to patients without CMV-related hospitalization.
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http://dx.doi.org/10.1080/03007995.2019.1664827DOI Listing
January 2020

Cost-Effectiveness of Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis at Intermediate Risk.

Circulation 2019 02;139(7):877-888

Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City (S.J.B., K.W., E.A.M., D.J.C.).

Background: In patients with severe aortic stenosis (AS) at intermediate surgical risk, treatment with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) results in similar rates of death or stroke at 2 years. Whether TAVR is cost-effective compared with SAVR for intermediate-risk patients remains uncertain.

Methods: Between 2011 and 2014, 3110 intermediate-risk AS patients were treated with TAVR or SAVR in the PARTNER 2 trial (Placement of Aortic Transcatheter Valves 2). A total of 2032 patients were randomized to receive TAVR using the SAPIEN XT valve (XT-TAVR) or SAVR in the PARTNER 2A trial, whereas the PARTNER S3i registry included an additional 1078 patients treated with TAVR using the SAPIEN 3 valve (S3-TAVR), which offers a lower delivery profile and sealing skirt designed to reduce paravalvular regurgitation compared with XT-TAVR. Procedural costs were estimated using measured resource utilization. Other in-trial costs were assessed by linkage of trial data with Medicare claims (n=2333) or by linear regression models for unlinked patients (n=682). Health utilities were estimated using the EQ-5D at baseline and 1, 12, and 24 months. Using a Markov model informed by in-trial costs, utilities, and survival data, lifetime cost-effectiveness from the perspective of the US healthcare system was estimated in terms of cost per quality-adjusted life-year gained.

Results: Although procedural costs were ≈$20 000 higher with TAVR than SAVR, total cost differences for the index hospitalization were only $2888 higher with XT-TAVR ( P=0.014) and were $4155 lower with S3-TAVR ( P<0.001) owing to reductions in length of stay with TAVR. Follow-up costs were significantly lower with XT-TAVR (Δ=-$9304; P<0.001) and S3-TAVR (Δ=-$11 377; P<0.001) than with SAVR. Over a lifetime horizon, TAVR was projected to lower total costs by $8000 to $10 000 and to increase quality-adjusted survival by 0.15 to 0.27 years. XT-TAVR and S3-TAVR were found to be economically dominant compared with SAVR in 84% and 97% of bootstrap replicates, respectively.

Conclusions: Among intermediate-risk AS patients, TAVR is projected to be economically dominant from the perspective of the US healthcare system by providing both greater quality-adjusted life expectancy and lower long-term costs than SAVR. If long-term data demonstrate comparable late mortality with TAVR and SAVR, these findings suggest that TAVR might be the preferred treatment strategy for intermediate-risk AS patients based on both clinical and economic considerations.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01314313.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035236DOI Listing
February 2019

Association of Same-Day Discharge After Elective Percutaneous Coronary Intervention in the United States With Costs and Outcomes.

JAMA Cardiol 2018 11;3(11):1041-1049

M&H Research, LLC, San Antonio, Texas.

Importance: Same-day discharge (SDD) after elective percutaneous coronary intervention (PCI) is associated with lower costs and preferred by patients. However, to our knowledge, contemporary patterns of SDD after elective PCI with respect to the incidence, hospital variation, trends, costs, and safety outcomes in the United States are unknown.

Objective: To examine (1) the incidence and trends in SDD; (2) hospital variation in SDD; (3) the association between SDD and readmissions for bleeding, acute kidney injury (AKI), acute myocardial infarction (AMI), or mortality at 30, 90, and 365 days after PCI; and (4) hospital costs of SDD and its drivers.

Design, Setting, And Participants: This observational cross-sectional cohort study included 672 470 patients enrolled in the nationally representative Premier Healthcare Database who underwent elective PCI from 493 hospitals between January 2006 and December 2015 with 1-year follow-up.

Exposures: Same-day discharge, defined by identical dates of admission, PCI procedure, and discharge.

Main Outcomes And Measures: Death, bleeding requiring a blood transfusion, AKI and AMI at 30, 90, or 365 days after PCI, and costs from hospitals' perspective, inflated to 2016.

Results: Among 672 470 elective PCIs, 221 997 patients (33.0%) were women, 30 711 (4.6%) were Hispanic, 51 961 (7.7%) were African American, and 491 823 (73.1%) were white. The adjusted rate of SDD was 3.5% (95% CI, 3.0%-4.0%), which increased from 0.4% in 2006 to 6.3% in 2015. We observed substantial hospital variation for SDD from 0% to 83% (median incidence rate ratio, 3.82; 95% CI, 3.48-4.23), implying an average (median) 382% likelihood of SDD at one vs another hospital. Among SDD (vs non-SDD) patients, there was no higher risk of death, bleeding, AKI, or AMI at 30, 90, or 365 days. Same-day discharge was associated with a large cost savings of $5128 per procedure (95% CI, $5006-$5248), driven by reduced supply and room and boarding costs. A shift from existing SDD practices to match top-decile SDD hospitals could annually save $129 million in this sample and $577 million if adopted throughout the United States. However, residual confounding may be present, limiting the precision of the cost estimates.

Conclusions And Relevance: Over 2006 to 2015, SDD after elective PCI was infrequent, with substantial hospital variation. Given the safety and large savings of more than $5000 per PCI associated with SDD, greater and more consistent use of SDD could markedly increase the overall value of PCI care.
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http://dx.doi.org/10.1001/jamacardio.2018.3029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583057PMC
November 2018

Costs Associated With Access Site and Same-Day Discharge Among Medicare Beneficiaries Undergoing Percutaneous Coronary Intervention: An Evaluation of the Current Percutaneous Coronary Intervention Care Pathways in the United States.

JACC Cardiovasc Interv 2017 02;10(4):342-351

University of Texas Southwestern Medical Center, Dallas, Texas.

Objectives: The aim of this study was to examine the independent impact of various care pathways, including those involving transradial intervention (TRI) and same-day discharge (SDD) after elective percutaneous coronary intervention (PCI), on hospital costs.

Background: PCI is associated with costs of $10 billion annually. Alternative payment models for PCI are being implemented, but few data exist on strategies to reduce costs. Various PCI care pathways, including TRI and SDD, exist, but their association with costs and outcomes is unknown.

Methods: In total, 279,987 PCI patients eligible for SDD in the National Cardiovascular Data Registry CathPCI Registry linked to Medicare claims files were analyzed. Hospital costs in 2014 U.S. dollars were estimated using cost-to-charge ratios. Propensity scores for TRI and SDD, with propensity adjustment via inverse probability weighting, was performed.

Results: Of the 279,987 PCI procedures, TRI was used in 9.0% (13.5% of which were SDD), and SDD was used in 5.3% of cases (23.1% of which were TRI). TRI (vs. transfemoral intervention) was associated with lower adjusted costs of $916 (95% confidence interval [CI]: $778 to $1,035), as was SDD ($3,502; 95% CI: $3,486 to $3,902). The adjusted cost associated with TRI and SDD was $13,389 (95% CI: $13,161 to $13,607), while the cost associated with transfemoral intervention and non-same-day discharge was $17,076 (95% CI: $16,999 to $17,147), a difference of $3,689 (95% CI: $3,486 to $3,902; p < 0.0001). Shifting current practice from transfemoral intervention non-same-day discharge to TRI SDD by 30% could potentially save a hospital performing 1,000 PCIs each year $1 million and the country $300 million annually.

Conclusions: Among Medicare beneficiaries, TRI with SDD was independently associated with fewer complications and lower in-hospital costs. These findings have important implications for changing the current PCI care pathways to improve outcomes and reduce costs.
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http://dx.doi.org/10.1016/j.jcin.2016.11.049DOI Listing
February 2017

Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial).

Am J Cardiol 2016 Apr 1;117(7):1127-34. Epub 2016 Feb 1.

Duke University Medical Center, Durham, North Carolina.

Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT-AF.
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http://dx.doi.org/10.1016/j.amjcard.2016.01.039DOI Listing
April 2016

Association between health status and long-term mortality after percutaneous revascularization of peripheral artery disease.

Catheter Cardiovasc Interv 2016 May 19;87(6):1149-55. Epub 2016 Feb 19.

Saint Luke's Mid America Heart Institute, Kansas City, Missouri.

Objectives: To explore the association of health status change and long-term survival among patients with symptomatic peripheral artery disease (PAD).

Background: Early gains in health status after successful endovascular therapy (EVT) for symptomatic PAD can be maintained up to 1 year. Whether such health status improvements are associated with long-term survival benefits is unknown.

Methods: Between February 2001 and August 2004, 258 patients with symptomatic PAD treated with EVT participated in a prospective study evaluating baseline and 1 year health status using the Peripheral Artery Questionnaire (range 0-100, higher scores = better). All-cause mortality was assessed for all patients at a median of 9.4 years following EVT.

Results: The mean age at enrollment was 68 ± 11 years; 61% were male, 97% were Caucasian, and 38% had diabetes. Patients with a clinically meaningful health status improvement (≥8 points) 1 year after their index procedure (79%) were identified as responders. Responders had a significantly better 10 year survival compared with nonresponders (60% vs 38%, p = 0.025). Responder status was associated with a survival advantage that persisted in risk-adjusted analysis (adjusted hazard ratio for long-term mortality, 0.66 [95% CI, 0.45-0.97]; p = 0.036).

Conclusions: Among patients with symptomatic PAD undergoing EVT, improvement of PAD-specific health status at 1 year follow-up was associated with improved long-term survival. Whether additional treatment for patients with poor response to EVT could improve long-term survival warrants further investigation. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ccd.26442DOI Listing
May 2016

Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden.

J Am Soc Nephrol 2016 Jan 30;27(1):305-13. Epub 2015 Jul 30.

The Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas; Department of Internal Medicine, Division of Nephrology & Hypertension, University of Kansas Medical Center, Kansas City, Kansas;

Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r(2)=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 μM [54.8-133.0 μM] for dialysis-dependent patients versus 3.3 μM [3.1-6.0 μM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min-max] 71.2 μM [29.2-189.7 μM] pretransplant versus 11.4 μM [8.9-20.2 μM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 μM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography.
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http://dx.doi.org/10.1681/ASN.2014111063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696571PMC
January 2016

The process of development of a prioritization tool for a clinical decision support build within a computerized provider order entry system: Experiences from St Luke's Health System.

Health Informatics J 2016 09 26;22(3):579-93. Epub 2015 Mar 26.

Saint Luke's Hospital, USA.

To establish a process for the development of a prioritization tool for a clinical decision support build within a computerized provider order entry system and concurrently to prioritize alerts for Saint Luke's Health System. The process of prioritizing clinical decision support alerts included (a) consensus sessions to establish a prioritization process and identify clinical decision support alerts through a modified Delphi process and (b) a clinical decision support survey to validate the results. All members of our health system's physician quality organization, Saint Luke's Care as well as clinicians, administrators, and pharmacy staff throughout Saint Luke's Health System, were invited to participate in this confidential survey. The consensus sessions yielded a prioritization process through alert contextualization and associated Likert-type scales. Utilizing this process, the clinical decision support survey polled the opinions of 850 clinicians with a 64.7 percent response rate. Three of the top rated alerts were approved for the pre-implementation build at Saint Luke's Health System: Acute Myocardial Infarction Core Measure Sets, Deep Vein Thrombosis Prophylaxis within 4 h, and Criteria for Sepsis. This study establishes a process for developing a prioritization tool for a clinical decision support build within a computerized provider order entry system that may be applicable to similar institutions.
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http://dx.doi.org/10.1177/1460458215571769DOI Listing
September 2016

Impact of transesophageal echocardiography on management in patients with suspected cardioembolic stroke.

Am J Cardiol 2014 Dec 26;114(12):1912-6. Epub 2014 Sep 26.

Saint Luke's Mid America Heart Institute, Kansas City Missouri. Electronic address:

Transesophageal echocardiography (TEE) is frequently performed in patients with acute ischemic cerebrovascular events to exclude a cardioembolic source. We aimed to determine the clinical impact of TEE on management. This is a retrospective single-center study of 1,458 consecutive patients hospitalized with acute ischemic stroke or transient ischemic attack who underwent TEE for evaluation of a suspected cardioembolic cause. Significant TEE findings were determined for each patient as recorded on the TEE report. The medical record was reviewed for baseline, clinical, and demographic variables and to determine whether significant management changes occurred as a result of the TEE findings. Potential significant changes in management included initiation of anticoagulation, placement of a patent foramen ovale (PFO) closure device, initiation of antibiotic therapy for endocarditis, surgical PFO closure, other cardiac surgery, and coil embolization of a pulmonary arteriovenous malformation. A significant change in management occurred in 243 patients (16.7%); 173 (71%) underwent treatment for PFO with a percutaneous PFO closure device (n = 100), initiation of chronic systemic anticoagulation (n = 68), or surgical PFO closure (n = 5). Additional findings leading to a change in management included endocarditis (n = 20), aortic arch atheroma (n = 14), intracardiac thrombus (n = 13), pulmonary arteriovenous malformation (n = 2), aortic valve fibroelastoma (n = 2), other valve masses (n = 4), and miscellaneous causes (n = 15). In conclusion, in patients with suspected cardioembolic stroke, TEE findings led to a change in management in 16.7% of patients. Of these, most (71%) were directed at prevention of subsequent paradoxical emboli in patients with PFO.
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http://dx.doi.org/10.1016/j.amjcard.2014.09.035DOI Listing
December 2014

Costs of transradial percutaneous coronary intervention.

JACC Cardiovasc Interv 2013 Aug 17;6(8):827-34. Epub 2013 Jul 17.

Washington University School of Medicine, Barnes Jewish Hospital, St. Louis, Missouri, USA.

Objectives: This study sought to evaluate the costs of transradial percutaneous coronary intervention (TRI) and transfemoral percutaneous coronary intervention (TFI) from a contemporary hospital perspective.

Background: Whereas the TRI approach to percutaneous coronary intervention (PCI) has been shown to reduce access-site complications compared with TFI, whether it is associated with lower costs is unknown.

Methods: TRI and TFI patients were identified at 5 U.S. centers. The primary outcome was the cost of percutaneous coronary intervention (PCI) hospitalization, defined as cost on the day of PCI through hospital discharge. Cost was obtained from each hospital's cost accounting system. Independent costs of TRI were identified using propensity-scoring methods with inverse probability weighting. Secondary outcomes of interest were bleeding, in-hospital mortality, and length of stay, which were stratified by pre-procedural risk and PCI indication.

Results: In 7,121 PCI procedures performed from January 1, 2010, to March 31, 2011, TRI was performed in 1,219 (17%) patients and was associated with shorter lengths of stay (2.5 vs. 3.0 days; p < 0.001) and lower bleeding events (1.1% vs. 2.4%, adjusted odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.34 to 0.79; p = 0.002). TRI was associated with a total cost savings of $830 (95% CI: $296 to $1,364; p < 0.001), of which $130 (95% CI: -$99 to $361; p = 0.112) were procedural savings and $705 (95% CI: $212 to $1,238; p < 0.001) were post-procedural savings. There was an associated graded increase in savings among patients at higher predicted risk of bleeding: low risk: $642 (95% CI: $43 to $1,236; p = 0.035); moderate risk: $706 (95% CI: $104 to $1,308; p = 0.029); and high risk: $1,621 (95% CI: $271 to $2,971, p = 0.039).

Conclusions: TRI was associated with a cost savings exceeding $800 per patient relative to TFI. Increased adoption of TRI may result in cost savings at hospitals.
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http://dx.doi.org/10.1016/j.jcin.2013.04.014DOI Listing
August 2013

Association between bleeding events and in-hospital mortality after percutaneous coronary intervention.

JAMA 2013 Mar;309(10):1022-9

Department of Biostatistics, Saint Luke’sMid America HeartInstitute, Kansas City, Missouri 64111, USA.

Importance: Bleeding is the most common complication after percutaneous coronary intervention (PCI) and is associated with increased morbidity and health care costs. The incidence of bleeding-related mortality after PCI has not been described in a nationally representative population. Furthermore, the relationships among bleeding risk, bleeding site, and mortality are unclear.

Objectives: To describe the association between bleeding events and in-hospital mortality after PCI and to estimate the adjusted population attributable risk (estimated as the proportion of mortality risk associated with bleeding events), risk difference, and number needed to harm (NNH) for bleeding-related in-hospital mortality after PCI.

Design, Setting, And Patients: Data from 3,386,688 procedures in the CathPCI Registry performed in the United States between 2004 and 2011 were analyzed. The population attributable risk was calculated after adjustment for baseline demographic, clinical, and procedural variables. To calculate the NNH for bleeding-related mortality, a propensity-matched analysis was performed.

Main Outcome Measures: In-hospital mortality.

Results: There were 57,246 bleeding events (1.7%) and 22,165 in-hospital deaths (0.65%) in 3,386,688 PCI procedures. The adjusted population attributable risk for mortality related to major bleeding was 12.1% (95% CI, 11.4%-12.7%) in the entire CathPCI cohort. The propensity-matched population consisted of 56,078 procedures with a major bleeding event and 224 312 controls. In this matched cohort, major bleeding was associated with increased in-hospital mortality (5.26% vs 1.87%; risk difference, 3.39% [95% CI, 3.20%-3.59%]; NNH = 29 [95% CI, 28-31]; P < .001). The association between major bleeding and in-hospital mortality was observed in all strata of preprocedural bleeding risk (low: 1.62% vs 0.17%; risk difference, 1.45% [95% CI, 1.13%-1.77%], NNH = 69 [95% CI, 57-88], P < .001; intermediate: 3.27% vs 0.71%; risk difference, 2.56% [95% CI, 2.33%-2.79%], NNH = 39 [95% CI, 36-43], P < .001; and high: 8.16% vs 3.45%; risk difference, 4.71% [95% CI, 4.35%-5.07%], NNH = 21 [95% CI, 20-23], P < .001). Although both access-site and non-access-site bleeding were associated with increased in-hospital mortality (2.73% vs 1.87%; risk difference, 0.86% [95% CI, 0.66%-1.05%], NNH = 117 [95% CI, 95-151], P < .001; and 8.25% vs 1.87%; risk difference, 6.39% [95% CI, 6.04%-6.73%], NNH = 16 [95% CI, 15-17], P < .001, respectively), the NNH was lower for nonaccess bleeding.

Conclusions And Relevance: In a large registry of patients undergoing PCI, postprocedural bleeding events were associated with increased risk of in-hospital mortality, with an estimated 12.1% of deaths related to bleeding complications.
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http://dx.doi.org/10.1001/jama.2013.1556DOI Listing
March 2013

Comparison of costs between transradial and transfemoral percutaneous coronary intervention: a cohort analysis from the Premier research database.

Am Heart J 2013 Mar 15;165(3):303-9.e2. Epub 2012 Nov 15.

St. Lukes's Mid America Heart Institute, St Luke's Hospital, Kansas City, MO, USA.

Background: Transradial intervention (TRI) for percutaneous coronary intervention (PCI) is associated with shorter length of stay, fewer bleeding complications, and higher patient satisfaction. Less is known about the economic implications of TRI in contemporary practice.

Methods: This is a retrospective inpatient cohort analysis using medical data from the Premier research database (Premier Inc, Charlotte, NC), which contains approximately one-fifth of all acute care hospitalizations in the US annually. The database was queried to identify patients undergoing PCI from 2004 to 2009. Patients with TRI were identified by center-level charge codes for radial-specific devices and matched one-to-many with patients undergoing transfemoral intervention (TFI). Adjusted total hospitalization costs were compared between patients undergoing TRI and TFI. Patients were additionally classified by periprocedural risk of bleeding as low (<1%), moderate (1%-3%), and high (>3%).

Results: There were 609 TRI cases matched with 60,900 TFI cases. Total adjusted costs for TRI were $11,736 ± $6,748 vs $12,288 ± $23,418 for TFI, a difference of $553 favoring TRI (95% CI $45-$1,060, P = .033). Day-of-procedure costs were similar, at $17 higher for TRI compared with TFI (95% CI -$318 to $353, P = .37); however, costs from the following day until discharge were significantly lower for TRI (-$571, 95 % CI -$912 to $229, P = .001). Postprocedure costs were lower for patients with TRI vs patients with TFI at moderate (-$478, 95% CI -$887 to $69, P = .022) and high (-$917, 95% CI -$1,814 to $19, P = .045) risk of bleeding.

Conclusions: In a nationwide administrative hospital database, transradial compared with transfemoral PCI access was associated with lower average direct hospital costs and shorter length of hospital stay. Postprocedure costs associated with TRI were also lower in patients at greater bleeding risk.
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http://dx.doi.org/10.1016/j.ahj.2012.10.004DOI Listing
March 2013

Clinical factors associated with left ventricular ejection fraction disparity in patients with left ventricular dysfunction undergoing multimodality imaging.

Mo Med 2012 Nov-Dec;109(6):489-92

Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA.

Drug and device therapy for heart failure is increasingly determined based on left ventricular ejection fraction. Significant disparity frequently exists between echocardiographic and nuclear scintigraphic techniques, even when testing is performed nearly simultaneously in clinically stable patients. In 119 patients with left ventricular dysfunction who underwent both echocardiography and stress testing with nuclear imaging within seven days (but with significant disparity in reported left ventricular ejection fraction), we identified four clinical variables which were associated with left ventricular ejection fraction difference. These clinical variables included atrial fibrillation, left ventricular hypertrophy, severe mitral regurgitation and paced rhythm.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179602PMC
March 2013

Management of hyperglycemia with the administration of intravenous exenatide to patients in the cardiac intensive care unit.

Endocr Pract 2013 Jan-Feb;19(1):81-90

Saint Luke's Mid America Heart Institute University of Missouri-Kansas City, Kansas City, MO 64111, USA.

Objective: To evaluate the feasibility, effectiveness, and safety of intravenous exenatide to control hyperglycemia in the cardiac intensive care unit (CICU).

Methods: A prospective, single-center, open-label, nonrandomized pilot study. Forty patients admitted to the CICU with glucose levels of 140 to 400 mg/dL received intravenous exenatide as a bolus followed by a fixed dose infusion for up to 48 hours. Exenatide effectiveness was benchmarked to two historical insulin infusion cohorts, one (INT) with a target glucose of 90 to 119 mg/dL (n = 84) and the other (MOD) with a target of 100 to 140 mg/dL (n = 71).

Results: Median admission glucose values were 185.5 mg/dL (161.0, 215.5), 259.0 mg/dL (206.0, 343.0), and 189.5 mg/dL (163.5, 245.0) in the exenatide, MOD, and INT groups, respectively (P<.001). Steady state glucose values were similar between the exenatide (132.0 mg/dL [110.0, 157.0]) and the MOD groups (127.0 mg/dL [105.0, 161.0], P = .15), but lower in the INT group (105.0 mg/dL [92.0, 128.0], P<.001 for exenatide versus INT). Median (IQR) time to steady state was 2.0 hours (1.5, 5.0) in the exenatide group compared to 12.0 hours (7.0, 15.0) in the MOD group (P<.001) and 3.0 hours (1.0, 5.0) in the INT group (P = .80 for exenatide versus INT). Exenatide was discontinued in 3 patients after failure to achieve glycemic control. No episodes of severe hypoglycemia (<50 mg/dL) occurred in patients who received exenatide. Nausea was reported by 16 patients and vomiting by 2 patients.

Conclusion: Intravenous exenatide is effective in lowering glucose levels in CICU patients, but its use may be limited by nausea.
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http://dx.doi.org/10.4158/EP12196.ORDOI Listing
August 2013

Prevalence of grade II and III obesity among patients hospitalized with cardiovascular diagnoses in 2002 v. 2009.

Mo Med 2012 Sep-Oct;109(5):397-401

Saint Luke's Mid America Heart Institute of Kansas City, USA.

Background: The prevalence of obesity has increased markedly over the past four decades; however, some reports suggest a recent plateau. There is little information available regarding recent changes in obesity prevalence among patients hospitalized with cardiovascular disease.

Objective: To define obesity trends among patients hospitalized with cardiovascular disease between 2002 and 2009 at an academic medical center.

Methods: This is a retrospective database analysis of patients admitted with cardiovascular diagnoses in 2002 versus 2009. Using ICD-9 codes, the study population was generated. Body mass index (BMI) was calculated by dividing weight in kilograms by height in meters squared (Quetelet index). Patients were assigned to 1 of 5 BMI categories: normal weight (BMI < 19-24.99), overweight (BMI 25-29.99), Grades I obesity (BMI 30-34.99), Grade II obesity (BMI 35-39.99), and Grade III obesity (BMI > 40). Patient demographics are compared with Student's T-tests for continuous data and chi2 tests for categorical data. Logistic regression models were developed in the overall cohort to ascertain differences in obesity grades I, II & III between the two time points with age, gender, race and primary ICD-9 code included as covariates. The logistic regression models were then repeated for each primary ICD-9 code.

Results: Patients admitted with cardiovascular diagnoses in 2002 (n = 1271) and 2009 (n = 1576) were stratified by BMI categories. Over this period of nine years, obesity prevalence increased significantly from 28.5% to 38.4% of patients. In particular, Grades II and III obesity increased markedly from 2002 to 2009 (7.6% versus 9.9%, and 2.7% versus 7.5%; unadjusted p = 0.04, p < 0.001 and adjusted p = 0.09 and p < 0.0001 respectively). Individuals with Grade III obesity had a higher incidence of arrhythmias, coronary heart disease, and valvular heart disease.

Conclusions: Grade II and III obesity has markedly increased among patients admitted to our hospital with major cardiovascular diagnoses in the period 2002 to 2009. With respect to hospitalized patients, the obesity epidemic is still on a steeply rising trajectory, especially for the extremely obese categories.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179769PMC
November 2012

Effect of renal transplantation for chronic renal disease on left ventricular mass.

Am J Cardiol 2012 Jul 5;110(2):254-7. Epub 2012 Apr 5.

Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA.

Chronic kidney disease is associated with an increased left ventricular (LV) mass. Few data are available regarding the effect of renal transplantation on LV mass regression or the clinical factors associated with LV mass regression. Patients with ≥1 year of chronic kidney disease followed by successful renal transplantation were identified. All patients underwent echocardiography ≥6 months before transplantation with repeat echocardiography ≥1 year after transplantation. An experienced echocardiographer, who was unaware of the clinical data, performed all linear measurements in the parasternal long-axis projection, including systolic and diastolic LV chamber dimensions and LV wall thickness. The LV mass was calculated as follows: 0.8 × {1.04 [(LV internal dimension at end diastole + posterior wall thickness at end diastole + LV wall thickness at the cardiac base for the anteroseptum)(3) - (LV internal dimension at end diastole)(3)]} + 0.6 g. Candidate clinical variables for an association with LV mass regression were assembled, including age, gender, race, donor type, renal disease etiology, medications (insulin, oral hypoglycemics, antihypertensives, statins, and antirejection medications), and co-morbidities. Patients were separated into 2 groups according to presence and absence of LV mass regression. A total of 105 patients (mean age 54 years; 58 men) were included in the study with a mean follow-up of 1.7 years. Of the 105 patients, 57 had significant LV mass regression (mean difference -37.2 ± 31.3 g/m(2)) and 48 had no significant regression (mean difference 15.7 ± 17.1 g/m(2)). The extent of the LV mass before transplantation was the only predictor of mass regression after transplantation (odds ratio 1.50, 95% confidence interval 1.26 to 1.80). In conclusion, significant LV mass regression is present in most patients after renal transplantation. The extent of the LV mass before transplantation was the only clinical predictor of regression.
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http://dx.doi.org/10.1016/j.amjcard.2012.02.067DOI Listing
July 2012

Stratification of risk in thin cap fibroatheromas using peak plaque stress estimates from idealized finite element models.

Med Eng Phys 2012 Nov 17;34(9):1330-8. Epub 2012 Feb 17.

Saint Luke's Mid America Heart Institute, Kansas City, MO, United States.

Thin cap fibroatheroma (TCFA) in coronary arteries is believed to be associated with plaque rupture leading to cardiovascular death and non-fatal myocardial infarction. Catheter-based imaging platforms can identify TCFAs but detection algorithms lack specificity. Here we report results of an exploratory study of the variability in TCFA plaque attributes and effects on peak von Mises stress of TCFA using idealized finite element models. A total of 1272 idealized TCFA finite element models were developed by strategically varying attribute dimensions - external elastic membrane diameter, lumen diameter, necrotic core thickness, fibrous cap thickness, and necrotic core angle - obtained from a global registry of subjects undergoing percutaneous coronary intervention with Virtual Histology intravascular ultrasound. Peak stress exhibited parabolic or higher order proportionality with lumen diameter, sigmoidal proportionality with necrotic core thickness, inverse hyperbolic proportionality with fibrous cap thickness, and skewed sinusoidal proportionality with necrotic core angle. Each of these relationships was governed by highly sensitive, complex, and interdependent influences of various attributes on plaque stress. An over 7-fold increase in peak stress from 101 to 788kPa was observed in models of coronary dimensions commonly encountered in clinical practice. Peak stress of intramural TCFA within this common coronary artery subset did not exceed 300kPa for fibrous cap thickness greater than 100μm and necrotic core angle outside 90-120° range, indicating low risk of rupture. This exploratory study demonstrated the complex and interdependent influence of plaque attributes on the peak stress of TCFA.
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http://dx.doi.org/10.1016/j.medengphy.2011.12.024DOI Listing
November 2012

Percutaneous coronary intervention outcomes in US hospitals with varying structural characteristics: analysis of the NCDR®.

Am Heart J 2012 Feb;163(2):222-9.e1

Division of General Medicine, University of Iowa Carver College of Medicine, Iowa City, 52246, USA.

Background: In the United States, there continues to be debate about whether certain types of hospitals deliver improved patient outcomes. We sought to assess the association between hospital organizational characteristics and in-hospital outcomes for percutaneous coronary intervention (PCI).

Methods: Retrospective analysis of 2004 to 2007 data for 694 US hospitals participating in the CathPCI Registry(®). Our analysis focused on 1,113,554 patients who underwent PCI in 471 not-for-profit (NFP) hospitals, 131 major teaching hospitals, 79 for-profit (FP) hospitals, and 13 physician-owned specialty hospitals. Outcomes included in-hospital mortality, stroke, bleeding, vascular injury, and a composite representing one or more of the individual complications. We used the current CathPCI Registry mortality risk model to calculate risk-standardized mortality ratios (RSMRs) for each category of hospital and compared hospital groupings for all patients in aggregate and in subgroups stratified by patients' indications for PCI.

Results: Patients treated in major teaching hospitals were younger, whereas FP hospitals performed a greater proportion of PCI for patients with ST-elevation myocardial infarction (P < .0001). Specialty hospitals treated patients with less acuity, including a lower proportion of patients with ST-elevation myocardial infarction. In unadjusted analyses, specialty hospitals had significantly lower rates of all adverse outcomes compared with NFP, teaching, and FP hospitals including in-hospital mortality (0.7%, 1.2%, 1.4%, and 1.4%, respectively; P < .001) and the composite end point (2.4%, 4.1%, 4.6%, and 4.3%, respectively; P < .001). In adjusted analyses, RSMR was significantly lower for specialty hospitals when compared with the other 3 groups for all patients in aggregate (RSMR 1.05%, 1.30%, 1.38%, 1.39%; P < .001); these differences remained clinically significant but were no longer statistically significant in subgroup analyses.

Conclusions: Specialty hospitals appear to have lower rates of most adverse outcomes for PCI. Specialty hospitals may have developed expertise in narrow procedural areas that could be adapted to the larger population of general hospitals.
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http://dx.doi.org/10.1016/j.ahj.2011.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273843PMC
February 2012

Indications for percutaneous coronary interventions performed in US hospitals: a report from the NCDR®.

Am Heart J 2012 Feb;163(2):214-21.e1

Division of General Medicine, University of Iowa Carver College of Medicine, Iowa City, USA.

Background: There are many factors hypothesized as contributing to overuse of percutaneous coronary intervention (PCI) in the United States, including financial ties between physicians and hospitals, but empirical data are lacking. We examined PCI indications in not-for-profit (NFP), major teaching, for-profit (FP), and physician-owned specialty hospitals.

Methods: A retrospective cohort study of 1,113,554 patients who underwent PCI in 694 hospitals (NFP 471, teaching 131, FP 79, specialty 13) participating in the CathPCI Registry® between January 1, 2004, and December 31, 2007. Percutaneous coronary intervention indications derived from American College of Cardiology Guidelines were classified as survival benefit (patients with primary reperfusion for ST-elevation myocardial infarction), potential quality of life benefit (patients with non-ST-elevation myocardial infarction, acute coronary syndrome (ACS), positive stress test, or chest pain), or unclear indications (patients receiving PCI without an obvious potential survival or quality of life benefit).

Results: The percentage of PCI performed for unclear indications was somewhat higher for specialty hospitals (5.1% of all procedures) as compared with other hospital categories (FP 4.7%, NFP 4.2%, major teaching 4.5%; P < .001). Overall, 17% of hospitals had ≥20% of their total PCI procedures performed for unclear indications, but the proportion of FP, NFP, major teaching, and specialty hospitals reaching this threshold was not statistically different (20%, 16%, 17%, and 15%, respectively; P = .84).

Conclusions: A small proportion of PCI procedures were performed in patients with unclear indications, but there was wide variation across hospitals. On average, specialty hospitals performed more PCIs for unclear indications. Efforts to reduce variability should be pursued.
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http://dx.doi.org/10.1016/j.ahj.2011.08.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273846PMC
February 2012

Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome.

BMC Med Genet 2011 Sep 29;12:127. Epub 2011 Sep 29.

Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA.

Background: Genome-wide association studies (GWAS) have identified new candidate genes for the occurrence of acute coronary syndrome (ACS), but possible effects of such genes on survival following ACS have yet to be investigated.

Methods: We examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for premature myocardial infarction for their association with post-ACS mortality among 811 whites recruited from university-affiliated hospitals in Kansas City, Missouri. We then sought replication of a positive genetic association in a large, racially diverse cohort of myocardial infarction patients (N = 2284) using Kaplan-Meier survival analyses and Cox regression to adjust for relevant covariates. Finally, we investigated the apparent association further in 6086 additional coronary artery disease patients.

Results: After Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality hazard (P = 0.007). The recessive A/A genotype was of borderline significance in an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P = 0.052), but this finding was not confirmed in independent cohorts (N = 6086).

Conclusions: We found no support for the hypothesis that the GWAS-identified variants in this study substantially alter the probability of post-ACS survival. Large-scale, collaborative, genome-wide studies may be required in order to detect genetic variants that are robustly associated with survival in patients with coronary artery disease.
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http://dx.doi.org/10.1186/1471-2350-12-127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190329PMC
September 2011

Percutaneous transluminal angioplasty: association between depressive symptoms and diminished health status benefits.

Vasc Med 2011 Aug;16(4):260-6

Saint Luke's Mid America Heart and Vascular Institute, Kansas City, MO 64111, USA.

Depressive symptoms are known to compromise health status in cardiac disease, but this relationship has not been described in peripheral artery disease (PAD). Depressive symptoms (PHQ-9) and disease-specific health status (Peripheral Artery Questionnaire, PAQ) were assessed in 242 PAD patients undergoing percutaneous transluminal angioplasty (PTA) at baseline and 1 year. Patients were classified by baseline and follow-up depression status (moderate-severe depressive symptoms = PHQ ≥ 10). Changes were categorized as no depression/improvement of depression versus persistent/worsened depression. At baseline, 20% of patients were depressed; at 1 year, 17% of patients experienced persistent/worsened depression. Although this group improved on most PAQ subscales, they improved to a significantly lesser degree than those without depressive symptoms or those who improved by 1 year (p-values < 0.05). Baseline depressive symptoms (B(per 5-point increment) = -11.9, 95% CI -15.3, -8.5, p < 0.0001) and changes in depression were independently associated with a decrease in 1-year health status (B(per 5-point increment) = -11.7, 95% CI -14.3, -9.2, p < 0.0001). In conclusion, depressive symptoms are associated with less improvement in health status 1 year after undergoing a peripheral endovascular revascularization (PER) as compared with those having no depression or whose depressive symptoms improve. Efforts to improve depression detection and treatment among patients with PAD may improve the health status outcomes of these patients.
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http://dx.doi.org/10.1177/1358863X11415568DOI Listing
August 2011

Tissue characterisation of atherosclerotic plaque in the left main: an in vivo intravascular ultrasound radiofrequency data analysis.

EuroIntervention 2011 Jul;7(3):347-52

Saint Luke's Mid America Heart and Vascular Institute, Kansas City, MO 64111, USA.

Aims: To characterise plaque phenotypes in the left main stem (LMS) and the proximal left anterior descending (LAD) coronary artery using virtual histology assisted intravascular ultrasound (VH-IVUS).

Methods And Results: Patients with IVUS pullbacks including no less than the proximal 30 mm of the LAD and through the ostium of the left main were identified from a global IVUS registry. Plaque composition and phenotype frequency in the LMS and five consecutive non-overlapping 6 mm segments in the LAD were studied, resulting in six analysed segments per patient. There were 74 patients (72% male, mean age 65 years). The median LMS length was 5.4 mm (IQR 2.8-8.7 mm). The percent of fibrofatty plaque was greater in the LMS compared to the proximal LAD segments (27.9% [20.0-39.2] vs. 17.3% [12.2-23.1], p<0.001). Dense calcium and necrotic core content was less prevalent in the LMS compared to the LAD segments (2.5% [0.9-4.7] vs. 7.9% [4.1-12.3], p<0.001; and 8.0% [3.7-11.8] vs. 14% [9.2-17.9], p<0.001). The frequency of thin cap fibroatheroma (TCFA) was higher in the LAD compared with LMS (0% vs. 16.9% [4.9-34.5], p<0.001). Within the LAD, TCFA was most frequently observed in the second 6 mm segment, 12 mm from the ostium.

Conclusions: TCFA was present more frequently in the proximal LAD than LMS, supporting the notion that plaque rupture occurs in non-uniform locations throughout the coronary tree and preferentially spares the LMS.
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http://dx.doi.org/10.4244/EIJV7I3A59DOI Listing
July 2011

Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies.

Diab Vasc Dis Res 2011 Jul 8;8(3):237-40. Epub 2011 Jun 8.

We assessed the cardiovascular safety of liraglutide, a glucagon-like peptide-1 receptor agonist, using existing clinical data. Patient-level results from all completed phase 2 and 3 studies from the liraglutide clinical development programme were pooled to determine rates of major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, stroke. MACE were identified by querying the study database using Medical Dictionary for Regulatory Activities (MedDRA) terms combined with serious adverse events recorded by study investigators. Broad, narrow, and custom groups of MedDRA queries were used. Candidate events from each query were independently adjudicated post hoc. In 15 studies (6638 patients; 4257 liraglutide treated), there were 114 patients with MACE identified using the broad MedDRA query. Of these, 44 were classified as serious adverse events and 39 were adjudicated as MACE. The incidence ratio for adjudicated broad/serious MACE associated with liraglutide was 0.73 (95% CI 0.38-1.41) versus all comparator drugs (metformin, glimepiride, rosiglitazone, insulin glargine, placebo), within cardiovascular safety limits defined by the United States Food & Drug Administration for diabetes therapies under current investigation.
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http://dx.doi.org/10.1177/1479164111408937DOI Listing
July 2011

Changes in myocardial ischemic burden following percutaneous coronary intervention of chronic total occlusions.

Catheter Cardiovasc Interv 2011 Sep 16;78(3):337-43. Epub 2011 Mar 16.

Mid America Heart and Vascular Institute, St. Luke's Hospital, Kansas City, Missouri, USA.

Objectives: We assessed the potential for percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) to decrease myocardial ischemia and established objective criteria to predict post-procedure improvement.

Background: Optimal treatment for CTO of coronary arteries is controversial, and selection criteria for PCI of CTO are subjective.

Methods: All patients undergoing CTO PCI at a single center between 2002 and 2007 were included if myocardial perfusion imaging (MPI) was performed within 12 ± 3 months before and a follow-up study within 12 ± 3 months after PCI. Average summed difference scores were calculated and converted to percent ischemic myocardium to classify patients as having normal/minimal, mild, moderate, or severe ischemia. A significant improvement in ischemia following PCI was classified as an absolute ≥5% decrease in ischemic myocardium. Receiver operating characteristic (ROC) curves were used to identify ischemic thresholds predictive of decreased and increased ischemic burden on follow-up MPI.

Results: In 301 patients, average baseline ischemic burden was 13.1% ± 11.9% and decreased to 6.9% ± 6.5% (P < 0.001) during follow-up. Overall, 53.5% of patients met criteria for improvement following PCI. These patients were more likely to be male, without diabetes, with CTO in the left anterior descending artery, and classified as having high ischemic burden at baseline. ROC analysis identified a baseline 12.5% ischemic burden as optimal in identifying those most likely to have a significantly decreased ischemic burden post-PCI. Those with a baseline ischemic burden less than 6.25% were more likely to have an increased ischemic burden post-PCI.

Conclusions: Ischemic burden is reduced following CTO PCI, and the decrease is greater at high ischemic burden. A threshold of 12.5% ischemic burden is suggested as a criterion for performing PCI in the setting of CTO.
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http://dx.doi.org/10.1002/ccd.23002DOI Listing
September 2011
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