Predicting Prostate Cancer Molecular Subtype With Deep Learning on Histopathologic Images.

Microscopic examination of prostate cancer has failed to reveal a reproducible association between molecular and morphologic features. However, deep-learning algorithms trained on hematoxylin and eosin (H&E)-stained whole slide images (WSI) may outperform the human eye and help to screen for clinically-relevant genomic alterations. We created deep-learning algorithms to identify prostate tumors with underlying ETS-related gene (ERG) fusions or PTEN deletions using the following 4 stages: (1) automated tumor identification, (2) feature representation learning, (3) classification, and (4) explainability map generation. A novel transformer-based hierarchical architecture was trained on a single representative WSI of the dominant tumor nodule from a radical prostatectomy (RP) cohort with known ERG/PTEN status (n = 224 and n = 205, respectively). Two distinct vision transformer-based networks were used for feature extraction, and a distinct transformer-based model was used for classification. The ERG algorithm performance was validated across 3 RP cohorts, including 64 WSI from the pretraining cohort (AUC, 0.91) and 248 and 375 WSI from 2 independent RP cohorts (AUC, 0.86 and 0.89, respectively). In addition, we tested the ERG algorithm performance in 2 needle biopsy cohorts comprised of 179 and 148 WSI (AUC, 0.78 and 0.80, respectively). Focusing on cases with homogeneous (clonal) PTEN status, PTEN algorithm performance was assessed using 50 WSI reserved from the pretraining cohort (AUC, 0.81), 201 and 337 WSI from 2 independent RP cohorts (AUC, 0.72 and 0.80, respectively), and 151 WSI from a needle biopsy cohort (AUC, 0.75). For explainability, the PTEN algorithm was also applied to 19 WSI with heterogeneous (subclonal) PTEN loss, where the percentage tumor area with predicted PTEN loss correlated with that based on immunohistochemistry (r = 0.58, P = .0097). These deep-learning algorithms to predict ERG/PTEN status prove that H&E images can be used to screen for underlying genomic alterations in prostate cancer.

Cerebral Embolic Protection and Outcomes of Transcatheter Aortic Valve Replacement: Results From the Transcatheter Valve Therapy Registry.

BACKGROUND: Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), which has persisted despite refinements in technique and increased operator experience. While cerebral embolic protection devices (EPDs) have been developed to mitigate this risk, data regarding their impact on stroke and other outcomes after TAVR are limited. METHODS: We performed an observational study using data from the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients were included if they underwent elective or urgent transfemoral TAVR between January 2018 and December 2019. The primary outcome was in-hospital stroke. To adjust for confounding, the association between EPD use and clinical outcomes was evaluated using instrumental variable analysis, a technique designed to support causal inference from observational data, with site-level preference for EPD use within the same quarter of the procedure as the instrument. We also performed a propensity score-based secondary analysis using overlap weights. RESULTS: Our analytic sample included 123 186 patients from 599 sites. The use of EPD during TAVR increased over time, reaching 28% of sites and 13% of TAVR procedures by December 2019. There was wide variation in EPD use across hospitals, with 8% of sites performing >50% of TAVR procedures with an EPD and 72% performing no procedures with an EPD in the last quarter of 2019. In our primary analysis using the instrumental variable model, there was no association between EPD use and in-hospital stroke (adjusted relative risk, 0.90 [95% CI, 0.68-1.13]; absolute risk difference, -0.15% [95% CI, -0.49 to 0.20]). However, in our secondary analysis using the propensity score-based model, EPD use was associated with 18% lower odds of in-hospital stroke (adjusted odds ratio, 0.82 [95% CI, 0.69-0.97]; absolute risk difference, -0.28% [95% CI, -0.52 to -0.03]). Results were generally consistent across the secondary end points, as well as subgroup analyses. CONCLUSIONS: In this nationally representative observational study, we did not find an association between EPD use for TAVR and in-hospital stroke in our primary instrumental variable analysis, and found only a modestly lower risk of in-hospital stroke in our secondary propensity-weighted analysis. These findings provide a strong basis for large-scale randomized, controlled trials to test whether EPDs provide meaningful clinical benefit for patients undergoing TAVR.

Cell Cycle Progression Score, but Not Phosphatase and Tensin Homolog Loss, Is an Independent Prognostic Factor for Metastasis in Intermediate- and High-risk Prostate Cancer in Men Treated With and Without Salvage Radiotherapy.

PURPOSE: The prognostic value for metastasis of the cell-cycle progression score and phosphatase and tensin homolog haven't been evaluated jointly in contemporary men with exclusively intermediate- or high-risk prostate cancer. We evaluated associations of cell-cycle progression and phosphatase and tensin homolog with metastasis-free survival in contemporary intermediate/high-risk prostate cancer patients overall, and intermediate/high-risk men receiving salvage radiotherapy. MATERIALS AND METHODS: In a case-cohort of 209 prostatectomy patients with intermediate/high-risk prostate cancer, and a cohort of 172 such men who received salvage radiotherapy, cell-cycle progression score was calculated from RNA expression, and phosphatase and tensin homolog was analyzed by immunohistochemistry. Proportional hazards regression, weighted for case-cohort design or unweighted for the salvage radiotherapy cohort, was used to evaluate associations of cell-cycle progression, phosphatase and tensin homolog with metastasis-free survival. Improvement in model discrimination was evaluated with the concordance index. RESULTS: In the case-cohort 41 men had metastasis, and 17 developed metastasis in the salvage radiotherapy cohort, at median follow-up of 3 and 4 years, respectively. For both case-cohort and salvage radiotherapy cohort, cell-cycle progression was independently associated with metastasis-free survival after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical: hazard ratio (95% confidence interval) = 3.11 (1.70-5.69) and 1.85 (1.19-2.85), respectively. Adding cell-cycle progression to Cancer of the Prostate Risk Assessment Post-Surgical increased the concordance index from 0.861 to 0.899 (case-cohort), and 0.745 to 0.819 (salvage radiotherapy cohort). Although statistically significant in univariate analyses, phosphatase and tensin homolog was no longer significant after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical. Analysis of interaction with National Comprehensive Cancer Network risk group showed that cell-cycle progression had the strongest effect among unfavorable intermediate-risk men. CONCLUSIONS: In the first study to evaluate metastasis risk associated with cell-cycle progression and phosphatase and tensin homolog in exclusively intermediate/high-risk prostate cancer, and in such men with salvage radiotherapy, cell-cycle progression but not phosphatase and tensin homolog was associated with significantly increased 2- to 3-fold risk of metastasis after Cancer of the Prostate Risk Assessment Post-Surgical adjustment.

Radial versus femoral access for left main percutaneous coronary intervention: An analysis from the Veterans Affairs Clinical, Reporting, and Tracking Program.

OBJECTIVES: We aimed to compare clinical characteristics and procedural outcomes of left main percutaneous interventions (LM-PCI) by transradial (TRA) versus transfemoral (TFA) approach in the VA healthcare system. BACKGROUND: TRA for percutaneous coronary intervention (PCI) is steadily increasing. However, the frequency and efficacy of TRA for LM-PCI remain less studied. METHODS: All LM-PCIs performed in the VA healthcare system were identified for fiscal year 2008 through 2018. Patients' baseline characteristics and procedure-related variables were compared by access site. Both short- and long-term clinical outcomes were analyzed using propensity score matching. RESULTS: A total of 4004 LM-PCI were performed in the VA via either radial or femoral access from 2008 to 2018. Among these, 596 (14.9%) LM PCIs were performed via TRA. Use of TRA for LM-PCI increased from 2.2% to 31.5% over the study period. Propensity matched outcome analysis, comparing TRA versus TFA, showed a similar procedural success (98.4% for TRA vs. 97.8% for TFA; RR: 1.01 [0.98, 1.03]) and 1-year major adverse cardiovascular events (MACE) (25.9% for TRA vs. 26.8% TFA; RR: 0.96 [0.74, 1.25]). There were no statistically significant differences among secondary outcomes analyses including major bleeding. CONCLUSION: Use of TRA for LM-PCI has been steadily increasing in the VA healthcare system. These findings demonstrate similar procedural success and 1-year MACE across access strategies, suggesting an opportunity to continue increasing TRA use for LM-PCI.

Orbital atherectomy of calcified coronary ostial lesions.

OBJECTIVES: To evaluate the feasibility and safety of coronary orbital atherectomy (OA) for the treatment of calcified ostial lesions. BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly being completed in complex patients and lesions. OA is effective for severely calcified coronary lesions; however, there is a dearth of evidence on the use of OA in ostial lesions, especially with long-term outcome data. METHODS: Data were obtained from a retrospective analysis of patients who underwent OA of heavily calcified ostial lesions followed by stent implantation from December 2010 to June 2019 at two high-volume PCI centers. Kaplan-Meier analysis was utilized to assess the primary endpoints of 30-day, 1-year, and 2-year freedom-from (FF) major adverse cardiac events (MACE: death, myocardial infarction, or target vessel revascularization), stroke, and stent thrombosis (ST). RESULTS: A total of 56 patients underwent OA to treat heavily calcified ostial coronary lesions. The mean age was 72 years with a high prevalence of diabetes (55%) and heart failure (36%), requiring hemodynamic support (14%). There was high FF angiographic complications (93%), and at 30-day, 1-year, and 2-year, a high FF-MACE (96%, 91%, and 88%), stroke (98%, 96%, and 96%), and ST (100%), respectively. CONCLUSIONS: This study represents the largest real-world experience of coronary OA use in heavily calcified ostial lesions with long-term outcomes over 2 years. The main finding in this retrospective analysis is that, despite the complex patients and lesions included in this analysis, OA appears to be a feasible and safe treatment option for calcified coronary ostial lesions.

Decision Support Needs for Patients with Severe Symptomatic Aortic Stenosis.

Social workers in healthcare settings often support patient decision-making processes for complex medical decisions. The objective of this study was to examine decision support needs for patients considering aortic valve replacement (AVR) for aortic stenosis. Seventeen qualitative interviews were conducted to explore treatment decision experiences of patients who accepted AVR. Analysis was conducted using a mixed inductive-deductive approach. Fear was a prevalent response for most participants in the face of AVR. Two general paths of decision making emerged: an "active" information seeking approach, or a "passive" simplicity seeking approach. Patients with unique clinical presentations felt alienated by the decision-making process. Acknowledging fear while understanding different decision-making styles provide opportunities for social workers and other members of multidisciplinary teams to support complex patient decisions.

Potential unrealized mortality benefit of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transport-2 inhibitors: A report from the Veterans Health Administration Clinical Assessment, Reporting and Tracking program.

AIM: To assess the unrealized potential of glucagon-like peptide-1 receptor agonist (GLP-1RA) or sodium-glucose co-transport-2 inhibitor (SGLT2i) use to reduce mortality in veterans with type 2 diabetes (T2D), coronary artery disease (CAD), and other characteristics congruent with clinical trial cohorts that established the efficacy of these agents. METHODS: Veterans with T2D and CAD on angiography in 2014 who were untreated with either a GLP-1RA or a SGLT2i were assessed for key eligibility criteria of the LEADER (GLP-1RA) and EMPA-REG OUTCOME (SGLT2i) trials. Trial hazard ratios and 95% confidence intervals for all-cause death were applied to deaths observed in veterans through 2018 to estimate the potential benefit of GLP-1RA or SGLT2i use. RESULTS: Median observation was 4.3 years. Of 15 987 veterans with T2D and CAD, 1186 (7.4%) were excluded for GLP-1RA or SGLT2i treatment, and 1386 lacked glycated haemoglobin measurement. Of the remaining 13 415 patients, 4103 (30.1%) and 5313 (39.6%) fulfilled the key criteria for the LEADER and EMPA-REG OUTCOME trials, respectively. Death occurred in 1009 (24.6%) of LEADER-eligible patients and 1335 (25.1%) of EMPA-REG OUTCOME-eligible patients. Under treatment with liraglutide in LEADER-eligible veterans, a 3.5% (0.7%-6.2%) potential absolute mortality reduction, corresponding to 144 (28-253) fewer deaths (0.88 [0.17-1.56] per 100 person-years), might have been expected. Similarly, under treatment with empagliflozin in EMPA-REG OUTCOME-eligible veterans, a 7.9% (4.5%-10.8%) potential absolute mortality reduction, corresponding to 418 (230-573) fewer deaths (1.98 [1.14-2.72] per 100 person-years), might have been expected. CONCLUSIONS: This analysis indicates unrealized opportunities to reduce mortality in selected veterans with T2D and CAD via increased GLP-1RA and SGLT2i use.

Lactoferrin CpG Island Hypermethylation and Decoupling of mRNA and Protein Expression in the Early Stages of Prostate Carcinogenesis.

Lactoferrin (LTF) is an iron-binding protein canonically known for its innate and adaptive immune functions. LTF may also act as a tumor suppressor with antiproliferative action. LTF is inactivated genetically or epigenetically in various cancers, and a CpG island spanning the transcriptional start site of LTF is hypermethylated in prostate cancer cell lines. We, therefore, hypothesized that LTF expression is silenced via CpG island hypermethylation in the early stages of prostate tumorigenesis carcinogenesis. Targeted methylation analysis was performed using a combination of methylated-DNA precipitation and methylation-sensitive restriction enzymes, and laser-capture microdissection followed by bisulfite sequencing on DNA isolated from prostate tissue samples, including both primary and metastatic disease. LTF mRNA in situ hybridization and LTF protein immunohistochemistry were also performed. We report that the LTF CpG island is frequently and densely methylated in high-grade prostatic intraepithelial neoplasia, primary prostate carcinoma, and metastases. We further report a decoupling of lactoferrin mRNA and protein expression, including in lesions where LTF mRNA has presumably been silenced via CpG island methylation. We conclude that LTF mRNA expression is silenced in prostate tumorigenesis via hypermethylation, supporting a role for LTF as a prostate cancer tumor suppressor gene. Likewise, the frequency at which the LTF CpG island is methylated across samples suggests it is an important and conserved step in prostate cancer initiation.

Laser atherectomy and drug-coated balloons for the treatment of femoropopliteal in-stent restenosis: 2-Year outcomes.

BACKGROUND: Femoropopliteal (FP) artery is one of the most anatomically challenging areas for sustained stent patency. The incidence of FP in-stent restenosis (ISR) is estimated at 50% at 24 months. Prior studies have shown that lesion debulking with laser atherectomy (LA) combined with drug coated balloon (DCB) have superior outcomes compared to LA + balloon angioplasty (BA) ISR, but there have not been studies evaluating 2-year outcomes. METHODS: This was a dual-center retrospective cohort study that compared patients with FP-ISR treated with LA + DCB versus LA + BA. Cox regression analysis was used to examine 2-year outcomes of target lesion revascularization (TLR) and the composite outcome of TLR or restenosis. Multivariable analysis was performed for clinical and statistically significant (in the univariate analysis) variables. RESULTS: One hundred and seventeen consecutive patients with Tosaka II (n = 32) and III (n = 85) ISR were analyzed. Sixty-six patients were treated with LA + DCB and 51 with LA + BA. The LA + DCB group had more lesions with moderate to severe calcification (58% vs. 13%; p < .0001). The LA + DCB group was more likely to be treated with the use of embolic protection devices (64% vs. 23%, p < .001) and cutting balloons (61% vs. 6%, p < .001). Bail-out stenting rates were lower in the LA + DCB group (32% vs. 57%, p = .008). LA + DCB was superior (HR: 0.57; 95% CI: 0.34-0.9, p = .027) for the composite outcome of 2-year TLR or restenosis. The 12-month KM estimates for freedom from TLR or restenosis were 66% in the LA + DCB group versus 46% in the LA + BA group. The 24-month KM estimates were 45% in the LA + DCB group versus 24% in the LA + BA group. CONCLUSIONS: The combination of DCB + LA was associated with decreased rates of bail-out stenting and improved 2-year TLR or restenosis rates. Randomized clinical trials examining the DCB + LA combination for FP-ISR are needed.

Two-Year Outcomes of Orbital Atherectomy Combined With Drug-Coated Balloon Angioplasty for Treatment of Heavily Calcified Femoropopliteal Lesions.

Purpose: To examine whether the combination of orbital atherectomy (OA) and drug-coated balloons (DCB) can lead to superior procedural and 2-year outcomes compared with DCB only in heavily calcified femoropopliteal (FP) lesions. Materials and Methods: A retrospective chart review was conducted to identify patients treated with DCB only or OA+DCB for de novo FP lesions at a single center over a 4-year period (2014-2017). In the observation period, 113 patients met the inclusion criteria: 63 treated with DCB only (mean age 69.0±8.6 years; 62 men) vs 50 treated with OA+DCB (mean age 70.3±7.1 years; 48 men). The OA+DCB group had higher calcification rates (78% with severe calcification vs 37% in the DCB only group). Propensity score matching (PSM) was used to adjust for baseline differences between the 2 groups. Cox regression analysis was used to compare the follow-up outcomes between lesions treated with OA+DCB vs DCB only. Results: No difference in procedural complications or success was found. After PSM adjustment, the OA+DCB group was associated with lower bailout stenting rates (39.4% vs 66.7% in the DCB only group; p=0.026). The 2 groups had similar long-term outcomes, although the OA+DCB arm had a trend toward reduced TLR rates that did not reach statistical significance. The Kaplan-Meier estimates for 2-year freedom from TLR were 76.1% for the OA+DCB group vs 55.5% for the DCB only group (p=0.109). Conclusion: OA+DCB is a safe and effective combination for the treatment of calcified FP lesions. The combined therapy decreased the bailout stenting rates in the adjusted analysis. Larger cohorts and randomized trials are needed to examine OA efficacy in FP lesions.

Temporal trends in the management and clinical outcomes of lower extremity arterial thromboembolism within a national Veteran population.

Lower extremity arterial thromboembolism is associated with significant morbidity and mortality. We sought to establish temporal trends in the incidence, management and outcomes of lower extremity arterial thromboembolism within the Veterans Affairs Healthcare System (VAHS). We identified patients admitted to VAHS between 2003 and 2014 with a primary diagnosis of lower extremity arterial thromboembolism. Medical and procedural management were ascertained from pharmaceutical and administrative data. Subsequent rates of major adverse limb events (MALE), major adverse cardiovascular events (MACE), and mortality were calculated using Cox proportional hazards models. From 2003 to 2014, there were 10,636 patients hospitalized for lower extremity thromboembolism across 140 facilities, of which 8474 patients had adequate comorbid information for analysis. Age-adjusted incidence decreased from 7.98 per 100,000 patients (95% CI: 7.28-8.75) in 2003 to 3.54 (95% CI: 3.14-3.99) in 2014. On average, the likelihood of receiving anti-platelet or anti-thrombotic therapy increased 2.3% (95% CI: 1.2-3.4%) per year during this time period and the likelihood of undergoing endovascular revascularization increased 4.0% (95% CI: 2.7-5.4%) per year. Clinical outcomes remained constant over time, with similar rates of MALE, MACE and mortality at 1 year after adjustment. In conclusion, the incidence of lower extremity arterial thromboembolism is decreasing, with increasing utilization of anti-thrombotic therapies and endovascular revascularization among those with this condition. Despite this evolution in management, patients with lower extremity thromboembolism continue to experience high rates of amputation and death within a year of the index event.

MYC drives overexpression of telomerase RNA (hTR/TERC) in prostate cancer.

Telomerase consists of at least two essential elements, an RNA component hTR or TERC that contains the template for telomere DNA addition and a catalytic reverse transcriptase (TERT). While expression of TERT has been considered the key rate-limiting component for telomerase activity, increasing evidence suggests an important role for the regulation of TERC in telomere maintenance and perhaps other functions in human cancer. By using three orthogonal methods including RNAseq, RT-qPCR, and an analytically validated chromogenic RNA in situ hybridization assay, we report consistent overexpression of TERC in prostate cancer. This overexpression occurs at the precursor stage (e.g. high-grade prostatic intraepithelial neoplasia or PIN) and persists throughout all stages of disease progression. Levels of TERC correlate with levels of MYC (a known driver of prostate cancer) in clinical samples and we also show the following: forced reductions of MYC result in decreased TERC levels in eight cancer cell lines (prostate, lung, breast, and colorectal); forced overexpression of MYC in PCa cell lines, and in the mouse prostate, results in increased TERC levels; human TERC promoter activity is decreased after MYC silencing; and MYC occupies the TERC locus as assessed by chromatin immunoprecipitation (ChIP). Finally, we show that knockdown of TERC by siRNA results in reduced proliferation of prostate cancer cell lines. These studies indicate that TERC is consistently overexpressed in all stages of prostatic adenocarcinoma and that its expression is regulated by MYC. These findings nominate TERC as a novel prostate cancer biomarker and therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Patient and lesion-specific characteristics predict risk of major adverse cardiovascular events among patients with previous percutaneous coronary intervention undergoing noncardiac surgery.

OBJECTIVES: To identify predictors of major adverse cardiovascular outcomes (MACE) among patients with prior percutaneous coronary intervention (PCI) who require noncardiac surgery. BACKGROUND: Patients with prior PCI who undergo noncardiac surgery have an increased risk of postoperative MACE, but few studies have examined the association of PCI lesion characteristics with subsequent operative risk. METHODS: Patients were identified using the VA Clinical Assessment, Reporting, and Tracking (CART) program. Patients who underwent noncardiac surgery within 2 years after stent placement were linked to VA and non-VA surgical records. A multivariable logistic regression model was developed to identify predictors of postoperative MACE. RESULTS: Among 12,621 patients with a history of prior PCI who underwent subsequent noncardiac surgery, 570 (4.5%) developed postoperative MACE. The median time from stent placement to surgery was 368 days (IQR 181-528). The strongest predictors of postoperative MACE were urgency of the operation, revised cardiac risk index, the indication for the prior PCI, and timing of the surgery after the PCI. Lesion characteristics independently associated with postoperative MACE included PCI to a distal (AOR 1.43, 95% CI 1.11-1.83) or ostial lesion (AOR 1.52, 95% CI 1.11-2.08), and lesion calcification (AOR 1.29, 95% CI 1.03-1.61), but stent length and target vessel were not independently associated with outcomes. Placement of a bare metal stent was also an independent predictor of MACE after noncardiac surgery (AOR 1.29, 95% CI 1.06-1.57). CONCLUSIONS: While patient and operative characteristics are the strongest predictors of MACE after noncardiac surgery, specific lesion characteristics including ostial or distal lesion location and calcification are novel risk factors for postoperative MACE. © 2016 Wiley Periodicals, Inc.

Triple Antithrombotic Therapy and Outcomes in Post-PCI Patients Undergoing Non-cardiac Surgery.

BACKGROUND: Triple therapy, or the use of anticoagulants with dual antiplatelet therapy (DAPT), is often used to protect against ischemic events in post-percutaneous coronary intervention (PCI) patients with indications for anticoagulation, but is associated with increased bleeding. As both ischemic and bleeding risks increase in the perioperative period, the impact of triple therapy may be especially pronounced in patients undergoing surgery. Outcomes in this population are currently unknown. METHODS: We identified patients undergoing non-cardiac surgeries within 2 years of PCI in Veterans Affairs hospitals from 2004 to 2012. We compared perioperative major adverse cardiovascular and cerebrovascular events (MACCE: mortality, myocardial infarction, stroke, revascularization) and bleeding events (in-hospital bleeding, transfusion) between surgeries in patients prescribed triple therapy and DAPT, adjusting for clinical, demographic, and operative characteristics. RESULTS: Among 7811 surgeries, 391 (5.0 %) occurred in patients receiving triple therapy. 44 (11.3 %) MACCE and 107 (27.4 %) bleeding events occurred with surgeries in triple therapy patients, compared to 366 (4.9 %) MACCE and 980 (13.2 %) bleeding events in DAPT patients. After adjustment, surgery in triple therapy patients was associated with higher rates of MACCE [odds ratio (OR) 1.65, 95 % confidence interval (CI) 1.16-2.34] or bleeding (OR 1.52, 95 % CI 1.17-1.99) as compared to surgery in DAPT patients. CONCLUSIONS: One in twenty post-PCI patients undergoing non-cardiac surgery were on triple therapy. Surgery in these patients was associated with higher MACCE and bleeding events compared to surgery in patients on DAPT, independent of clinical and operative characteristics. These findings identify a high-risk population for surgery, which may warrant increased surveillance for adverse perioperative events.

Pre-operative echocardiography among patients with coronary artery disease in the United States Veterans Affairs healthcare system: A retrospective cohort study.

BACKGROUND: Echocardiography is not recommended for routine pre-surgical evaluation but may have value for patients at high risk of major adverse cardiovascular events (MACE). The objective of this study was to evaluate whether pre-operative echocardiography is associated with lower risk of post-operative MACE among patients with coronary artery disease. METHODS: Using administrative and registry data, we examined associations of echocardiography within 3 months prior to surgery with postoperative MACE (myocardial infarction, revascularization, or death within 30 days) among patients with coronary artery disease undergoing elective, non-cardiac surgeries in the United States Veterans Affairs healthcare system in 2000-2012. RESULTS: Echocardiography preceded 4,378 (16.4 %) of 26,641 surgeries. MACE occurred within 30 days following 944 (3.5 %) surgeries. A 10 % higher case-mix adjusted rate of pre-operative echocardiography assessed at the hospital level was associated with a hospital-level risk of MACE that was 1.0 % (95 % confidence interval [CI] 0.1 %, 2.0 %) higher overall and 1.7 % (95 % CI 0.2 %, 3.2 %) higher among patients with recent myocardial infarction, valvular heart disease, or heart failure. At the patient level, pre-operative echocardiography was associated with an odds ratio for MACE of 1.9 (95 % CI 1.7, 2.2) overall and 1.8 (95 % CI 1.5, 2.2) among patients with recent myocardial infarction, valvular heart disease, or heart failure adjusting for MACE risk factors. CONCLUSIONS: Pre-operative echocardiography was not associated with lower risk of post-operative MACE, even in a high risk population. Future guidelines should encourage pre-operative echocardiography only in specific patients with cardiovascular disease among whom findings can be translated into effective changes in care.

Contemporary Management Before Chronic Total Occlusion Percutaneous Coronary Interventions: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

BACKGROUND: Guidelines recommend maximal antianginal medical therapy before attempted coronary artery chronic total occlusion (CTO) percutaneous coronary intervention (PCI). The degree to which this occurs in contemporary practice is unknown. We aimed to characterize the frequency and variability of preprocedural use of antianginal therapy and stress testing within 3 months before PCI of CTO (CTO PCI) across a nationally integrated health care system. METHODS: We identified patients who underwent attempted CTO PCI from January 2012 to September 2018 within the Veterans Affairs Healthcare System. Patients were categorized by management before CTO PCI: presence of ≥2 antianginals, stress testing, and ≥2 antianginals and stress testing within 3 months of PCI attempt. Multivariable logistic regression and inverse propensity weighting were used for adjustment before trimming, with median odds ratios calculated for variability estimates. RESULTS: Among 4250 patients undergoing attempted CTO PCI, 40% received ≥2 antianginal medications and 24% underwent preprocedural stress testing. The odds of antianginal therapy with more than one medication before CTO PCI did not change over the years of the study (odds ratio [OR], 1.0 [95% CI, 0.97-1.04]), whereas the odds of undergoing preprocedural stress testing decreased (OR, 0.97 [95% CI, 0.93-0.99]), and the odds of antianginal therapy with ≥2 antianginals and stress testing did not change (OR, 0.98 [95% CI, 0.93-1.04]). Median odds ratios (MOR) showed substantial variability in antianginal therapy across hospital sites (MOR, 1.3 [95% CI, 1.26-1.42]) and operators (MOR, 1.35 [95% CI, 1.26-1.63]). Similarly, preprocedural stress testing varied significantly by site (MOR, 1.68 [95% CI, 1.58-1.81]) and operator (MOR, 1.80 [95% CI, 1.56-2.38]). CONCLUSIONS: Just under half of patients received guideline-recommended management before CTO PCI, with significant site and operator variability. These findings suggest an opportunity to reduce variability in management before CTO PCI.

Impact of Operator Volumes and Experience on Outcomes After Percutaneous Coronary Intervention: Insights From the Veterans Affairs Clinical Assessment, Reporting and Tracking (CART) Program.

BACKGROUND: Recent analyses of the volume-outcome relationship for percutaneous coronary intervention (PCI) have suggested a less robust association than previously reported. It is unknown if novel factors such as lifetime operator experience influence this relationship. OBJECTIVES: To assess the relationship between annual volumes and outcomes for PCI and determine whether lifetime operator experience modulates the association. METHODS: Annual PCI volumes for facilities and operators within the Veterans Affairs Healthcare System and their relationship with 30-day mortality following PCI were described. The influence of operator lifetime experience on the volume-outcome relationship was assessed. Hierarchical logistic regression was used to adjust for patient and procedural factors. RESULTS: 57,608 PCIs performed from 2013 to 2018 by 382 operators and 63 institutions were analyzed. Operator annualized PCI volume averaged 47.6 (standard deviation [SD] 49.1) and site annualized volume averaged 189.2 (SD 105.2). Median operator experience was 9.0 years (interquartile range [IQR] 4.0-15.0). There was no independent relationship between operator annual volume, institutional volume, or operator lifetime experience with 30-day mortality (p > 0.10). However, the interaction between operator volume and lifetime experience was associated with a marginal decrease in mortality (odds ratio [OR] 0.9998, 95% CI 0.9996-0.9999). CONCLUSIONS: There were no significant associations between facility or operator-level procedural volume and 30-day mortality following PCI in a nationally integrated healthcare system. There was a marginal association between the interaction of operator lifetime experience, operator annual volume, and 30-day mortality that is unlikely to be clinically relevant, though does suggest an opportunity to explore novel factors that may influence the volume-outcome relationship.

Association of Residual Ischemic Disease With Clinical Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: Anatomical scoring systems have been used to assess completeness of revascularization but are challenging to apply to large real-world datasets. OBJECTIVES: The aim of this study was to assess the prevalence of complete revascularization and its association with longitudinal clinical outcomes in the U.S. Department of Veterans Affairs (VA) health care system using an automatically computed anatomic complexity score. METHODS: Patients undergoing percutaneous coronary intervention (PCI) between October 1, 2007, and September 30, 2020, were identified, and the burden of prerevascularization and postrevascularization ischemic disease was quantified using the VA SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score. The association between residual VA SYNTAX score and long-term major adverse cardiovascular events (MACE; death, myocardial infarction, repeat revascularization, and stroke) was assessed. RESULTS: A total of 57,476 veterans underwent PCI during the study period. After adjustment, the highest tertile of residual VA SYNTAX score was associated with increased hazard of MACE (HR: 2.06; 95% CI: 1.98-2.15) and death (HR: 1.50; 95% CI: 1.41-1.59) at 3 years compared to complete revascularization (residual VA SYNTAX score = 0). Hazard of 1- and 3-year MACE increased as a function of residual disease, regardless of baseline disease severity or initial presentation with acute or chronic coronary syndrome. CONCLUSIONS: Residual ischemic disease was strongly associated with long-term clinical outcomes in a contemporary national cohort of PCI patients. Automatically computed anatomic complexity scores can be used to assess the longitudinal risk for residual ischemic disease after PCI and may be implemented to improve interventional quality.