Saphenous Vein Graft Pseudoaneurysm Treated With Covered Stenting.

Saphenous vein graft (SVG) pseudoaneurysms are an infrequent, but life-threatening complication of coronary artery bypass grafting (CABG) surgery if left untreated. Here, we discuss the case of a 77-year-old patient, with a prior history of CABG and transcatheter aortic valve implantation (TAVI), who was incidentally found on computed tomography angiography (CTA) to have a pseudoaneurysm of his SVG with an initial chief complaint of dizziness. Despite increasing reports of SVG pseudoaneurysm, there is no consensus on definitive treatment. Due to the high mortality risk of this patient with surgical intervention, a minimally invasive percutaneous coronary intervention was performed. The patient was effectively treated with two overlapping Viabahn-covered stents, which completely excluded the pseudoaneurysm. Follow-up imaging at two months showed two well-positioned overlapping self-expanding stents with total occlusion of the pseudoaneurysm.

Short partial doffs of release/relock sockets may effectively stabilize limb fluid volume in prosthesis users with transtibial amputation.

BACKGROUND: A challenge often faced by people with lower extremity amputation is management of prosthetic socket fit due to changes in fluid volume within their residual limb. Prior research suggests that intermittently doffing the prosthetic socket may help stabilize daily residual limb fluid volume. METHODS: To assess the effects of partial doff duration on residual limb fluid volume retention, participants with transtibial amputation were tested by walking on a treadmill in a controlled, laboratory setting under three conditions. An automated system to release the locking pin and enlarge the socket was used to produce the partial doffing. Percent limb fluid volume changes after partial doffing for 4 min (Short Rest) and for 10 min (Long Rest) were compared with no partial doffing (No Release). Limb fluid volume was monitored using bioimpedance analysis. FINDINGS: Mean percent fluid volume changes in the posterior region were  -1.2% for No Release, 2.7% for Short Rest, and 1.0% for Long Rest. Short and Long Rests had larger increases than No Release (P = 0.005 and 0.03, respectively); Short and Long Rests were not statistically different (P = 0.10). Eight of the thirteen participants experienced a higher percent fluid volume gain for both release protocols while four experienced a higher percent fluid volume gain for only one release protocol. INTERPRETATION: A partial doff duration as short as 4 min may be an effective strategy to stabilize limb fluid volume in prosthesis users with transtibial amputation. Trials in at-home settings should be pursued.

Using magnetic panels to enlarge a transtibial prosthetic socket.

A novel method is described to connect a prosthetic liner to the panels of an adjustable socket to facilitate limb fluid volume stabilization in prosthesis users. Magnets are placed in the socket panels, and iron powder is embedded in the user's prosthetic liner. When the magnet is in close proximity to the liner, a firm connection is formed. The system's capability to execute panel pull on transtibial prosthesis users was tested. The backs of the panels were supported by a bracket mounted to the external surface of the socket that allowed the radial position of the panels to be adjusted. Bench testing demonstrated an optimized strength-to-weight ratio using 1.27-cm thick annular-shaped magnets supported by 0.32-cm thick backplates. Testing on four people with transtibial amputation showed that the maximum socket increase achieved using magnetic panel pull ranged from 5.3% to 13.8% of the initial (panels flush) socket volume. The results indicate that magnetic panel pull induces a meaningful increase in socket volume during sitting. The clinical relevance is a novel strategy that may help stabilize prosthesis users' limb fluid volume over the day.

Midterm Durability and Structural Valve Degeneration of Transcatheter Aortic Valve Replacement in a Federal Facility.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR), previously reserved for patients of intermediate to prohibitive surgical risk, has now been expanded to patients of any surgical risk with severe aortic stenosis. Bioprostheses are prone to structural valve degeneration (SVD), a progressive and multifactorial process that limits valve durability. As the population undergoing TAVR shifts toward a lower-risk and younger profile, long-term durability is a crucial determinant for patient outcomes. Our objective was to determine the incidence and risk factors of SVD at midterm follow-up in a veteran TAVR population. METHODS: Patients undergoing TAVR at our federal facility were retrospectively evaluated for SVD and other endpoints with standardized consensus criteria. Multivariable Cox proportional hazards analysis was performed to evaluate risk factors for mortality and SVD. RESULTS: From 2013 to 2020, 344 patients (median age, 78 years) underwent TAVR. Survival from all-cause mortality was 91.3% at 1 year, 75.1% at 3 years, and 61.7% at 5 years. Cumulative freedom from SVD was 98.2% at 1 year, 96.5% at 3 years, and 93.7% at 5 years. All 13 patients with SVD met hemodynamic criteria, and 1 required intervention. Median time to hemodynamic SVD was 1.04 years. Independent risk factors for SVD included age (hazard ratio [HR] = 0.92, 95% confidence interval [CI]: 0.86 to 0.99) and valve size (HR = 0.19, 95% CI: 0.04 to 0.89). CONCLUSIONS: SVD was evident at a low but detectable rate at 5-year follow-up. Further understanding of TAVR biomechanics as well as continued longer-term follow-up will be essential for informing patient-specific risk of SVD.

Saphenous Vein Graft Failure: From Pathophysiology to Prevention and Treatment Strategies.

Saphenous vein grafts (SVGs) remain the most frequently used conduits in coronary artery bypass graft surgery (CABG). Despite advances in surgical techniques and pharmacotherapy, SVG failure rates remain high, often leading to repeat coronary revascularization. The no-touch SVG harvesting technique (minimal graft manipulation with preservation of vasa vasorum and nerves) reduces the risk of SVG failure, whereas the effect of the off-pump technique on SVG patency remains unclear. Use of buffered storage solutions, intraoperative graft flow measurement, careful selection of the target vessels, and physiological assessment of the native coronary circulation before CABG may also reduce the incidence of SVG failure. Perioperative aspirin and high-intensity statin administration are the cornerstones of secondary prevention after CABG. Dual antiplatelet therapy is recommended for off-pump CABG and in patients with a recent acute coronary syndrome. Intermediate (30%-60%) SVG stenoses often progress rapidly. Stenting of intermediate SVG stenoses failed to improve outcomes; hence, treatment focuses on strict control of coronary artery disease risk factors. Redo CABG is associated with higher perioperative mortality compared with percutaneous coronary intervention (PCI); hence, the latter is preferred for most patients requiring repeat revascularization after CABG. SVG PCI is limited by high rates of no-reflow and a high incidence of restenosis during follow-up. Drug-eluting and bare metal stents provide similar long-term outcomes in SVG PCI. Embolic protection devices reduce no-reflow and should be used when feasible. PCI of the corresponding native coronary artery is associated with better short- and long-term outcomes and is preferred over SVG PCI, if technically feasible.

Comparative Outcomes of Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Among Medicare Beneficiaries With Multivessel Coronary Artery Disease: An National Cardiovascular Data Registry Research to Practice Project.

[Figure: see text].

Development of the Minimalist Approach for Transcatheter Aortic Valve Replacement at a Veterans Affairs Medical Center.

OBJECTIVES: While a minimalist transcatheter aortic valve replacement (TAVR) approach has shown safety and efficacy at civilian hospitals, limited data exist regarding developing this approach at Veterans Affairs (VA) medical centers (VAMCs). We implemented TAVR with minimalist approach (MA) using conscious sedation (CS) with transthoracic echocardiography (TTE) and compared safety and outcomes with general anesthesia (GA) with transesophageal echocardiography (TEE) at a university-affiliated VAMC. METHODS: A total of 258 patients underwent transfemoral TAVR at a VAMC between November 2013 and October 2019. Ninety-three patients underwent GA/TEE and 165 patients underwent CS/TTE with dexmedetomidine and remifentanil. Propensity-score matching with nearest-neighbor matching was used to account for baseline differences, yielding 227 participants (81 GA, 146 CS). RESULTS: MA-TAVR had no effect on 30-day mortality or paravalvular leakage. No differences were found in permanent pacemaker implantation, major vascular complications, or postoperative hemodynamics. In this population, MA-TAVR did not reduce procedural time, hospital length of stay, or intensive care unit length of stay. CONCLUSIONS: Unlike civilian hospitals, MA with CS/TTE did not reduce overall length of stay in the veteran population; however, it was safe and effective for transfemoral TAVR without impacting clinical outcomes of mortality, major vascular complications, and paravalvular leakage.

Temporal Changes and Institutional Variation in Use of Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction With Multivessel Coronary Artery Disease in the United States: An NCDR Research to Practice Project.

Importance: After disparate results from observational and small randomized studies, the COMPLETE trial demonstrated superiority of multivessel (MV) percutaneous coronary intervention (PCI) over culprit-only PCI for ST-elevation myocardial infarction (STEMI). Objective: To describe temporal trends and institutional variation of MV PCI use for STEMI in the United States to inform how new evidence may influence clinical practice. Design, Setting, and Participants: This cohort study included STEMI admissions involving MV disease from 1598 institutions in the National Cardiovascular Data Registry CathPCI Registry from the third quarter of 2009 to the first quarter of 2018. An MV PCI was defined as a PCI to a nonculprit lesion within 45 days of the index procedure. Exposures: Multivessel PCI, defined as placement of coronary stents in 2 or more major epicardial vessels or the staged placement of 1 or more coronary stents in a major epicardial vessel distinct from the index culprit vessel, within 45 days of the index PCI. Main Outcomes and Measures: Outcomes included the proportional use of MV PCI among STEMI admissions with MV disease, and the timing of MV PCI (an index procedure, a staged procedure during index hospitalization, or a postdischarge procedure within 45 days). Results: Among 359 879 admissions with STEMI and MV disease, MV PCI was performed in 38.5% (n = 138 380; mean [SD] age of patients, 62.3 [12.3] years; 102 266 men [73.9%]) within 45 days. Of those receiving MV PCIs, 30.8% (n = 42 629) had a procedure performed during the index procedure, 31.6% (n = 43 696) as a staged procedure during the index hospitalization, and 37.6% (n = 52 055) within 45 days of discharge. Complete revascularization of all diseased arteries was performed in 76.2% (n = 105 389). From the third quarter of 2009 to the second quarter of 2013, MV PCI use declined by 10%, from 42.7% (3230 of 7572 cases) to a nadir of 32.7% (3386 of 10 342 cases), followed by an increase to 44.0% (5062 of 11 497 cases) by the fourth quarter of 2017. During this time, there was a 13.6% decline in use of postdischarge staged MV PCI (from 23.4% of STEMI cases [1772 of 7572 cases] in the third quarter of 2009 to 9.9% [1094 of 11 171 cases] in the fourth quarter of 2014) and an 12.5% increase in MV PCI performed during the index admission (from 19.3% [1458 of 7572 cases] in the third quarter of 2009 to 31.8% [3557 of 11 171 cases] in the first quarter of 2018). Multivessel PCI use varied substantially across institutions, with a median use of 37.9% (interquartile range, 30.0%-46.5%). Conclusions and Relevance: In this large, nationwide analysis, MV PCI use for patients with STEMI has been increasing through early 2018 but was used in the minority of patients and with wide variability across US institutions. The adoption of new trial results into guidelines and practice may further promote the growth of MV PCI.

Revascularization Practices and Outcomes in Patients With Multivessel Coronary Artery Disease Who Presented With Acute Myocardial Infarction and Cardiogenic Shock in the US, 2009-2018.

Importance: Cardiogenic shock after acute myocardial infarction (AMI) is associated with high mortality, particularly among patients with multivessel coronary artery disease. Recent evidence suggests that use of multivessel percutaneous coronary intervention (PCI) may be associated with harm. However, little is known about recent patterns of care and outcomes for this patient population. Objective: To evaluate patterns in the use of multivessel PCI vs culprit-vessel PCI in AMI and cardiogenic shock and outcomes in the US from 2009 to 2018. Design, Setting, and Participants: This cohort study identified all patients in the CathPCI Registry) with AMI and cardiogenic shock who had multivessel coronary artery disease and underwent PCI between July 1, 2009, and March 31, 2018. Exposures: Multivessel or culprit-vessel PCI for AMI and shock. Primary Outcomes and Measures: The primary outcome was in-hospital mortality. Temporal trends and hospital variation in PCI strategies were evaluated, while accounting for differences in case mix using hierarchical models. As a secondary outcome, the association of PCI strategy with postdischarge outcomes was evaluated in the subset of patients who were Medicare beneficiaries. Results: Of 64 301 patients (mean [SD] age, 66.4 [12.5] years; 20 366 [31.7%] female; 54 538 [84.8%] White) with AMI and shock at 1649 US hospitals, 34.9% had primary multivessel PCI. In the subgroup of 48 943 patients with ST-segment elevation myocardial infarction (STEMI), 31.5% underwent multivessel PCI. Between 2009 and 2018, this percentage increased by 6.7% per year for AMI and 5.8% for STEMI. Overall, multivessel PCI was associated with a greater adjusted risk of in-hospital complications (odds ratio [OR], 1.18; 95% CI, 1.14-1.23) and with greater in-hospital mortality in patients with STEMI (OR, 1.11; 95% CI, 1.06-1.16). Among Medicare beneficiaries, multivessel PCI use was not associated with postdischarge 1-year mortality (51.5% vs 49.8%; risk-adjusted OR, 0.97; 95% CI, 0.90-1.04; P = .37). Significant hospital variation was found in the use of multivessel PCI, with a higher multivessel PCI rate for similar patients across hospitals (median OR, 1.37; 95% CI, 1.33-1.41). Patients at hospitals with high rates of PCI in STEMI use had higher risk-adjusted in-hospital mortality (highest vs lowest hospital multivessel PCI quartile: OR, 1.10; 95% CI, 1.02-1.19). Conclusions and Relevance: This cohort study found that multivessel PCI was increasingly used as the revascularization strategy in AMI and shock and that hospitals that used multivessel PCI more, especially among patients with STEMI, had worse outcomes. With recent evidence suggesting harm with this strategy, there appears to be an urgent need to change practice and improve outcomes in this high-risk population.

Patient Risk Assessment for Transcatheter Aortic Valve Replacement at Veterans Health Administration Hospitals.

OBJECTIVE: To compare patient-level risk assessment at Veterans Affairs (VA) hospitals in patients undergoing transcatheter aortic valve replacement (TAVR) with patients included in the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) registry. METHODS: We retrospectively analyzed the outcomes of veterans with severe aortic stenosis (AS) receiving TAVR from 2012-2016 at eight VA hospitals and compared them with TVT registry outcomes from 2012-2015. Patients were identified via administrative data. Univariable and multivariable Cox proportional hazards models were used to examine 30-day and 1-year all-cause mortality, 30-day and 1-year transient ischemic attack/stroke rates, and permanent pacemaker (PPM) implantation rates. RESULTS: During the study period, a total of 726 veterans underwent TAVR including valve-in-valve procedures (n = 50). Patients were predominantly male (98.2%), with mean age of 78.5 ± 9.3 years; 49.1% were at prohibitive risk and 12.1% were at high risk for surgical aortic valve replacement; 30-day and 1-year all-cause mortality rates were 2.5% and 14.7%, respectively; 30-day and 1-year combined TIA/stroke rates were 6.5% and 13.5%, respectively. In the TVT registry, 15.8% and 37.8% of patients were at prohibitive and high risk, respectively; 30-day and 1-year mortality rates were 5.7% and 22.7%, respectively, and stroke rates were 2.1% and 4.0%, respectively. CONCLUSIONS: This report on TAVR risk assessment within the VA system demonstrates that despite a large proportion of patients classified as prohibitive risk, TAVR was associated with favorable 30-day and 1-year all-cause mortality rates when compared with published outcomes from the STS/ACC TVT registry.

Outcomes of Veterans Undergoing TAVR Within Veterans Affairs Medical Centers: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

OBJECTIVES: This study sought to describe clinical and procedural characteristics of veterans undergoing transcatheter aortic valve replacement (TAVR) within U.S. Department of Veterans Affairs (VA) centers and to examine their association with short- and long-term mortality, length of stay (LOS), and rehospitalization within 30 days. BACKGROUND: Veterans with severe aortic stenosis frequently undergo TAVR at VA medical centers. METHODS: Consecutive veterans undergoing TAVR between 2012 and 2017 were included. Patient and procedural characteristics were obtained from the VA Clinical Assessment, Reporting, and Tracking system. The primary outcomes were 30-day and 1-year survival, LOS >6 days, and rehospitalization within 30 days. Logistic regression and Cox proportional hazards analyses were performed to evaluate the associations between pre-procedural characteristics and LOS and rehospitalization. RESULTS: Nine hundred fifty-nine veterans underwent TAVR at 8 VA centers during the study period, 860 (90%) by transfemoral access, 50 (5%) transapical, 36 (3.8%) transaxillary, and 3 (0.3%) transaortic. Men predominated (939 of 959 [98%]), with an average age of 78.1 years. There were 28 deaths within 30 days (2.9%) and 134 at 1 year (14.0%). Median LOS was 5 days, and 141 veterans were rehospitalized within 30 days (14.7%). Nonfemoral access (odds ratio: 1.74; 95% confidence interval [CI]: 1.10 to 2.74), heart failure (odds ratio: 2.51; 95% CI: 1.83 to 3.44), and atrial fibrillation (odds ratio: 1.40; 95% CI: 1.01 to 1.95) were associated with increased LOS. Atrial fibrillation was associated with 30-day rehospitalization (hazard ratio: 1.79; 95% CI: 1.22 to 2.63). CONCLUSIONS: Veterans undergoing TAVR at VA centers are predominantly elderly men with significant comorbidities. Clinical outcomes of mortality and rehospitalization at 30 days and 1-year mortality compare favorably with benchmark outcome data outside the VA.

Effects of Family Demographics and the Passage of Time on Parents' Difficulty with Their Lesbian, Gay, or Bisexual Youth's Sexual Orientation.

Parents' responses to a child's sexual orientation are critical to shaping lesbian, gay, and bisexual (LGB) adolescents' health, but we know little about which families struggle most with having an LGB child. This study explored how parent responses to their LGB child varied by parent characteristics, child characteristics, and time passing. Parents of LGB youth aged 10-25 years (n = 1195) completed questions about themselves, their children, and their difficulty with having an LGB child. Parents with older children and African American and Latino parents reported the most difficulty. Parents who had known about a child's sexual orientation for more time reported less difficulty. However, these decreases in difficulty were only observed after 2 years, and parents reporting they had known for between 2 months and 2 years all reported similarly high levels of difficulty. Findings point to families most in need of intervention to improve parent responses and reduce adolescent risk.

Veterans Affairs Heart Team Experience With Transcatheter Aortic Valve Replacement and Minimally Invasive Surgical Aortic Valve Replacement.

OBJECTIVES: Aortic valve disease is prevalent in the veteran population. Transcatheter aortic valve replacement (TAVR) and minimally invasive surgical aortic valve replacement (MIAVR) are minimally invasive approaches predominantly performed at higher-volume cardiac centers. The study aim was to evaluate our experience with minimally invasive techniques at a Veterans Affairs Medical Center (VAMC), since outcomes from lower-volume federal facilities are relatively unknown. METHODS: This study examined retrospective data from 228 consecutive patients who underwent treatment for isolated aortic valve disease with MIAVR or TAVR via intent-to-treat at a VAMC between January 2011 and July 2017. Perioperative outcomes were analyzed using Stata version 15. RESULTS: Operative mortality was 1.1% for MIAVR and 0.7% for TAVR (Χ² P=.79). Median length of hospital stay was 10 days (interquartile range [IQR], 7-14 days) for MIAVR and 4 days for TAVR (IQR, 3-6 days; Mann-Whitney P<.001). Postoperative new-onset atrial fibrillation occurred in 52% of MIAVR patients and 5.2% of TAVR patients (Χ² P<.001). Stroke occurred in 2.2% of MIAVR patients and 3.0% of TAVR patients (Χ² P=.71). In patients who underwent MIAVR, 5.4% required placement of a permanent pacemaker postoperatively, compared with 14% of TAVR patients (Χ² P=.04). Mild paravalvular leak (PVL) affected 2.2% of MIAVR and 28% of TAVR patients, with moderate PVL reported in 2.2% of MIAVR and 3% of TAVR patients (Χ² P<.001). CONCLUSIONS: The VAMC heart team offers MIAVR and TAVR to veterans with isolated aortic valve disease, and has achieved excellent outcomes despite relatively lower case volumes. Both offer excellent hemodynamic results, with low mortality in a complex population.

Evolution of Veterans Affairs Transcatheter Aortic Valve Replacement Program: The First 100 Patients.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a widely established alternative to surgery in intermediate- and high-risk patients. TAVR program development within the Veterans Affairs (VA) system has been previously described. However, national TAVR registries do not capture VA outcomes data, and few data have been reported regarding TAVR outcomes at lower-volume federal institutions. The study aim was to demonstrate the evolution of a successful VA TAVR program. METHODS: A retrospective analysis was performed of the first 100 TAVR patients at San Francisco VA Medical Center. Mortality and major complications were evaluated. RESULTS: Between 25th November 2013 and 31st August 2016, a total of 100 TAVR procedures was performed at the authors' institution. The mean patient age was 79.7 ± 8.7 years. Patients underwent TAVR via percutaneous-transfemoral (n = 90), surgical cutdown-transfemoral (n = 8), or transapical (n = 2) approaches. The valve systems employed were Edwards SAPIEN (n = 16), SAPIEN XT (n = 31), SAPIEN 3 (n = 23), and Medtronic CoreValve (n = 16) and CoreValve Evolut R (n = 14). The overall device success was 96%. TAVR-in-TAVR was required in the remaining 4% of patients, and was successful. All-cause procedural mortality was 1%. Complications included tamponade (1%), stroke (2%), temporary hemodialysis (1%), vascular injuries requiring intervention (4%), and permanent pacemaker implantation (14%). There were no conversions to surgical aortic valve replacement. Twenty-two (22%) patients had mild, two (2%) had moderate, and none (0%) had severe paravalvular leakage. The post-procedure aortic valve gradient by echocardiography was 8.6 ± 4.5 mmHg. Follow up was 100% complete and survival was 99%, 93%, and 89% at one, six, and 12 months, respectively. CONCLUSIONS: Successful outcomes were demonstrated for a VA TAVR program that compared favorably with benchmarks established by the National Transcatheter Valve Therapies Registry. These results provide a necessary transparency of TAVR outcomes at a federal institution.

Socio-economic risk factors for early childhood underweight in Bangladesh.

BACKGROUND: Underweight is a major cause of global disease burden. It is associated with child mortality and morbidity, and its adverse impact on human performance and child survival is well recognized. Underweight is a major public health problem in Bangladesh, which is amongst the highest underweight prevalent countries in the world. The objectives of our study were to determine the national and regional prevalence rates of underweight and severe underweight in Bangladesh, and to investigate the association of socioeconomic and demographic factors with child underweight and severely underweight among children under the age of five living in Bangladesh. METHODS: We performed a cross sectional study using Multiple Indicators Cluster Survey 2012-13, Bangladesh data on 17,133 children under 5 years of age. Weight-for-age Z scores based upon World Health Organization (WHO) guidelines were used to define child underweight and severe underweight. The association of underweight and severe underweight with household socioeconomic factors and demographic characteristics was investigated using binary logistic regression model. RESULTS: An estimated 31.67% children were underweight and 8.81% children were severely underweight. Children of mothers with incomplete secondary education [Odds Ratio (OR) = 0.84, 95% CI: 0.75, 0.94] and mothers with completed secondary education [Odds Ratio (OR) = 0.77, 95% CI: 0.64, 0.93] were less likely to be underweight than children of uneducated mothers who had no formal schooling. A similar association exists for father's education, children from households in the highest wealth index quintile had lower likelihood of underweight [Odds Ratio (OR) = 0.44, 95% CI: 0.37, 0.53] than children from households in the lowest quintile. Consumption of non-iodized salt had higher risk of severe underweight for children aged between 24 and 35 months [Odds Ratio (OR) = 2.32, 95% CI: 1.80, 3.00]. Other risk factors of child severe underweight included living in Sylhet division and increases in the number of children under the age of five in a household. CONCLUSION: Underweight was associated with lower parental education, household position in lower wealth index, living in Sylhet division and consumption of non-iodized salt. Strategies are discussed considering the relative importance of risk factors for child underweight.

Prostaglandin E2 Increases Lentiviral Vector Transduction Efficiency of Adult Human Hematopoietic Stem and Progenitor Cells.

Gene therapy currently in development for hemoglobinopathies utilizes ex vivo lentiviral transduction of CD34+ hematopoietic stem and progenitor cells (HSPCs). A small-molecule screen identified prostaglandin E2 (PGE2) as a positive mediator of lentiviral transduction of CD34+ cells. Supplementation with PGE2 increased lentiviral vector (LVV) transduction of CD34+ cells approximately 2-fold compared to control transduction methods with no effect on cell viability. Transduction efficiency was consistently increased in primary CD34+ cells from multiple normal human donors and from patients with ß-thalassemia or sickle cell disease. Notably, PGE2 increased transduction of repopulating human HSPCs in an immune-deficient (nonobese diabetic/severe combined immunodeficiency/interleukin-2 gamma receptor null [NSG]) xenotransplantation mouse model without evidence of in vivo toxicity, lineage bias, or a de novo bias of lentiviral integration sites. These data suggest that PGE2 improves lentiviral transduction and increases vector copy number, therefore resulting in increased transgene expression. As a result, PGE2 may be useful in clinical gene therapy applications using lentivirally modified HSPCs.

Coronary atherectomy is associated with improved procedural and clinical outcomes among patients with calcified coronary lesions: Insights from the VA CART program.

OBJECTIVES: We sought to evaluate the prevalence of calcified coronary lesions and the association between the use of atherectomy and clinical outcomes. BACKGROUND: Calcified coronary arteries are associated with an increased risk of procedural complications during percutaneous coronary intervention (PCI). The outcomes of coronary atherectomy for adjunctive treatment of calcified coronary lesions are not well described. METHODS: We identified all patients treated for calcified coronary lesions at VA hospitals. A propensity weighted cohort was created for those treated with or without adjunctive atherectomy to evaluate the complications and outcomes between groups. RESULTS: From 2007 to 2015, 9,719 patients underwent single-vessel PCI for treatment of naïve native calcific coronary lesions. The proportion of patients undergoing revascularization of calcified lesions increased over the study period (P = 0.03) and 1,731 patients (18%) were treated with atherectomy. Adjunctive atherectomy was more likely to be used in high-risk lesions (76.5% vs. 46.8%, P < 0.001). After propensity weighting, coronary atherectomy was associated with a 38% decrease in the odds of procedural complications and a 54% decrease in the odds of clinical complications (both P = 0.005). There was no difference in rates of 2-year death (HR: 1.07; 95% CI: 0.92-1.24), myocardial infarction (HR: 0.96; 95% CI: 0.75-1.23) or target vessel revascularization (HR: 0.96; 95% CI: 0.78-1.19) CONCLUSIONS: Percutaneous treatment of calcified coronary lesions has increased over time. The adjunctive use of coronary atherectomy was associated with a reduction in procedural complications among patients with calcified coronary arteries. Two-year TVR, MI and overall mortality were similar between the two groups.

Outcomes of primary percutaneous coronary intervention in acute myocardial infarction due to unprotected left main thrombosis: The Asia-Pacific Left Main ST-Elevation Registry (ASTER).

INTRODUCTION: Prior studies of ULM STEMI have been confined to small cohorts. Recent registry data with larger patient cohorts have shown contrasting results. We aim to study the outcomes of patients with unprotected left main (ULM) ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). METHODS: The Asia-pacific left main ST-Elevation Registry (ASTER) is a multicenter retrospective registry involving 4 sites in Singapore, South Korea, and the United States. The registry included patients presenting with STEMI due to an ULM coronary artery culprit lesion who underwent emergency PCI. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events. RESULTS: A total of 67 patients (mean age 64.2 ± 12.8 years, 53 [79.1%] males) were included. The distal left main bifurcation was most commonly involved (85%, n = 57). Fifty one (76%) patients had TIMI 3 flow post-PCI. The in-hospital mortality rate was 47.8% (n = 32); 61% (n = 41) had cardiac failure, 4% (n = 3) had emergency coronary artery bypass grafting, 1% (n = 1) had a re-infarction, 3% (n = 2) had stroke and 55% (n = 37) had malignant ventricular arrhythmias. On multivariate analysis, predictors of in-hospital mortality included older age (odds ratio (OR) 1.085 (95% confidence interval (CI) 1.002-1.175), P = 0.044), diabetes mellitus (OR 10.882 (95%CI 11.074-110.287), P = 0.043) and absence of post-PCI TIMI 3 flow (OR 71.429 (95%CI 2.985-1000), P = 0.008). CONCLUSIONS: STEMI from culprit unprotected left main coronary artery stenosis is associated with significant mortality and morbidity. Emergency PCI provides an important treatment option in this high-risk group, but in-hospital mortality remains high.