Barriers to atrial fibrillation ablation during mitral valve surgery.

BACKGROUND: Nearly 40% of patients with atrial fibrillation (AF) undergoing mitral valve surgery do not receive concomitant ablation despite societal guidelines. We assessed barriers to implementation of this evidence-based practice through a survey of cardiac surgeons in 2 statewide quality collaboratives. METHODS: Adult cardiac surgeons across 2 statewide collaboratives were surveyed on their knowledge and practice regarding AF ablation. Questions concerning experience, clinical practice, case scenarios, and barriers to implementation were included. RESULTS: Among 66 respondents (66 of 135; 48.9%), the majority reported "very comfortable/frequently use" cryoablation (53 of 66; 80.3%) and radiofrequency (55 of 66; 83.3%). Only 12.1% (8/66) were not aware of the recommendations. Approximately one-half of the respondents reported learning AF ablation in fellowship (50.0%; 33 of 66) or attending courses (47.0%; 31 of 66). Responses to clinical scenarios demonstrated wide variability in practice patterns. One-half of the respondents reported no barriers; others cited increased cross-clamp time, excessive patient risk, and arrhythmia incidence as obstacles. Desired interventions included cardiology/electrophysiology support, protocols, pacemaker rate information, and education in the form of site visits, videos and proctors. CONCLUSIONS: Knowledge of evidence-based recommendations and practice patterns vary widely. These data identify several barriers to implementation of concomitant AF ablation and suggest specific interventions (mentorship/support, protocols, research, and education) to overcome these barriers.

Modeling an immune response to influenza A virus infection in alveolar epithelial cells.

Influenza A viruses (IAV) have been the cause of several influenza pandemics in history and are a significant threat for the next global pandemic. Hospitalized influenza patients often have excess interferon production and a dysregulated immune response to the IAV infection. Obtaining a better understanding of the mechanisms of IAV infection that induce these harmful effects would help drug developers and health professionals create more effective treatments for IAV infection and improve patient outcomes. IAV stimulates viral sensors and receptors expressed by alveolar epithelial cells, like RIG-I and toll-like receptor 3 (TLR3). These two pathways coordinate with one another to induce expression of type III interferons to combat the infection. Presented here is a queuing theory-based model of these pathways that was designed to analyze the timing and amount of interferons produced in response to IAV single stranded RNA and double-stranded RNA detection. The model accurately represents biological data showing the necessary coordination of the RIG-I and TLR3 pathways for effective interferon production. This model can serve as the framework for future studies of IAV infection and identify new targets for potential treatments.

Queueing theory model of mTOR complexes' impact on Akt-mediated adipocytes response to insulin.

A queueing theory based model of mTOR complexes impact on Akt-mediated cell response to insulin is presented in this paper. The model includes several aspects including the effect of insulin on the transport of glucose from the blood into the adipocytes with the participation of GLUT4, and the role of the GAPDH enzyme as a regulator of mTORC1 activity. A genetic algorithm was used to optimize the model parameters. It can be observed that mTORC1 activity is related to the amount of GLUT4 involved in glucose transport. The results show the relationship between the amount of GAPDH in the cell and mTORC1 activity. Moreover, obtained results suggest that mTORC1 inhibitors may be an effective agent in the fight against type 2 diabetes. However, these results are based on theoretical knowledge and appropriate experimental tests should be performed before making firm conclusions.

The impact of perioperative stroke and delirium on outcomes after surgical aortic valve replacement.

OBJECTIVE: The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days. METHODS: Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life. RESULTS: By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score >2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01). CONCLUSIONS: Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Queueing theory model of pentose phosphate pathway.

Due to its role in maintaining the proper functioning of the cell, the pentose phosphate pathway (PPP) is one of the most important metabolic pathways. It is responsible for regulating the concentration of simple sugars and provides precursors for the synthesis of amino acids and nucleotides. In addition, it plays a critical role in maintaining an adequate level of NADPH, which is necessary for the cell to fight oxidative stress. These reasons prompted the authors to develop a computational model, based on queueing theory, capable of simulating changes in PPP metabolites' concentrations. The model has been validated with empirical data from tumor cells. The obtained results prove the stability and accuracy of the model. By applying queueing theory, this model can be further expanded to include successive metabolic pathways. The use of the model may accelerate research on new drugs, reduce drug costs, and reduce the reliance on laboratory animals necessary for this type of research on which new methods are tested.

Pacemaker implantation associated with tricuspid repair in the setting of mitral valve surgery: Insights from a Cardiothoracic Surgical Trials Network randomized trial.

OBJECTIVES: In a recent trial, tricuspid annuloplasty (TA) during mitral valve surgery (MVS) for degenerative mitral regurgitation and moderate or less tricuspid regurgitation (TR) reduced the composite rate of death, reoperation for TR, or TR progression at 2 years. However, this benefit was counterbalanced by an increase in implantation of permanent pacemakers (PPMs). In this study, we analyzed the timing, indications, and risk factors for these implantations. METHODS: We randomized 401 patients (MVS alone = 203; MVS + TA = 198). Potential risk factors for PPMs were assessed using multivariable time-to-event models with death and PPM implantation for heart failure indications as competing risks. RESULTS: A PPM was implanted in 36 patients (9.6; 95% CI, 6.8-13.0) within 2 years of randomization, with 30/187 (16.0%) in the MVS + TA and 6/188 (3.2%) in the MVS groups (rate ratio, 5.08; 95% CI, 2.16-11.94; P < .001). Most (29/36; 80.6%) implantations occurred within 30 days postoperatively. Independent risk factors for PPM implantation within 2 years were TA (hazard ratio [HR], 5.94; 95% CI, 2.27-15.53; P < .001), increasing age (5 years, HR, 1.23; 95% CI, 1.01-1.52; P = .04), and left ventricular ejection fraction (LVEF; HR, 0.96; 95% CI, 0.92-0.99; P = .02). In the subset of TA recipients (n = 197), age (5 years, HR, 1.05; 95% CI, 1.00-1.10; P = .04) and LVEF (HR, 0.95; 95% CI, 0.91-0.99; P = .01) were associated with PPM within 2 years. CONCLUSIONS: Concomitant TA, age, and baseline LVEF were risk factors for PPM implantation in patients who underwent MVS for degenerative mitral regurgitation. Although TA was effective in preventing progression of TR, innovation is needed to identify ways to decrease PPM implantation rates.

Concomitant Tricuspid Repair in Patients with Degenerative Mitral Regurgitation.

BACKGROUND: Tricuspid regurgitation is common in patients with severe degenerative mitral regurgitation. However, the evidence base is insufficient to inform a decision about whether to perform tricuspid-valve repair during mitral-valve surgery in patients who have moderate tricuspid regurgitation or less-than-moderate regurgitation with annular dilatation. METHODS: We randomly assigned 401 patients who were undergoing mitral-valve surgery for degenerative mitral regurgitation to receive a procedure with or without tricuspid annuloplasty (TA). The primary 2-year end point was a composite of reoperation for tricuspid regurgitation, progression of tricuspid regurgitation by two grades from baseline or the presence of severe tricuspid regurgitation, or death. RESULTS: Patients who underwent mitral-valve surgery plus TA had fewer primary-end-point events than those who underwent mitral-valve surgery alone (3.9% vs. 10.2%) (relative risk, 0.37; 95% confidence interval [CI], 0.16 to 0.86; P = 0.02). Two-year mortality was 3.2% in the surgery-plus-TA group and 4.5% in the surgery-alone group (relative risk, 0.69; 95% CI, 0.25 to 1.88). The 2-year prevalence of progression of tricuspid regurgitation was lower in the surgery-plus-TA group than in the surgery-alone group (0.6% vs. 6.1%; relative risk, 0.09; 95% CI, 0.01 to 0.69). The frequencies of major adverse cardiac and cerebrovascular events, functional status, and quality of life were similar in the two groups at 2 years, although the incidence of permanent pacemaker implantation was higher in the surgery-plus-TA group than in the surgery-alone group (14.1% vs. 2.5%; rate ratio, 5.75; 95% CI, 2.27 to 14.60). CONCLUSIONS: Among patients undergoing mitral-valve surgery, those who also received TA had a lower incidence of a primary-end-point event than those who underwent mitral-valve surgery alone at 2 years, a reduction that was driven by less frequent progression to severe tricuspid regurgitation. Tricuspid repair resulted in more frequent permanent pacemaker implantation. Whether reduced progression of tricuspid regurgitation results in long-term clinical benefit can be determined only with longer follow-up. (Funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research; ClinicalTrials.gov number, NCT02675244.).

Progression of Tricuspid Regurgitation After Surgery for Ischemic Mitral Regurgitation.

BACKGROUND: Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain. OBJECTIVES: The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery. METHODS: Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years. RESULTS: Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04). CONCLUSIONS: After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

Risk for non-home discharge following surgery for ischemic mitral valve disease.

OBJECTIVES: To determine the frequency and risk factors for non-home discharge (NHD) and its association with clinical outcomes and quality of life (QOL) at 1 year following cardiac surgery in patients with ischemic mitral regurgitation (IMR). METHODS: Discharge disposition was evaluated in 552 patients enrolled in trials of severe or moderate IMR. Patient and in-hospital factors associated with NHD were identified using logistic regression. Subsequently, association of NHD with 1-year mortality, serious adverse events (SAEs), and QOL was assessed. RESULTS: NHD was observed in 30% (154/522) with 25% (n = 71/289) in moderate and 36% (n = 83/233) in patients with severe IMR (unadjusted P = .006), a difference not significant after including age (5-year change: adjusted odds ratio [adjOR], 1.52; 95% confidence interval [CI], 1.35-1.72; P < .001), diabetes (adjOR, 1.94; 95% CI, 1.27-2.94; P = .002), and previous heart failure (adjOR, 1.64; 95% CI, 1.06-2.52; P = .03). Odds of NHD were increased for patients with postoperative SAEs (adjOR, 1.85; 95% CI, 1.19-2.86; P = .01) but not based on type of cardiac surgery. Greater rates of death and SAEs were observed in NHD patients at 1 year: adjusted hazard ratio, 4.29 (95% CI, 2.14-8.59; P < .001) and adjusted rate ratio, 1.45 (95% CI, 1.03-2.02; P = .03), respectively. QOL did not differ significantly between groups. CONCLUSIONS: NHD is common following surgery for IMR, influenced by older age, diabetes, previous heart failure, and postoperative SAEs. These patients may be at greater risk of death and subsequent SAEs after discharge. Discussion of NHD with patients may have important implications for decision-making and guiding expectations following cardiac surgery.

Transcatheter mitral valve repair for functional mitral regurgitation: Evaluating the evidence.

OBJECTIVES: Two trials (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation Trial and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation Trial) were published in 2018 evaluating the effectiveness and safety of transcatheter repair for patients with heart failure with significant functional mitral regurgitation, which yielded different results. This article reviews the strength of the evidence, differences in trial designs, ethical and implementation implications, and delineates future research needs to help guide the appropriate dissemination of transcatheter repair for functional patients with mitral regurgitation. METHODS: The National Heart, Lung, and Blood Institute convened a workshop of interdisciplinary experts to address these objectives. RESULTS: Transcatheter repair of functional mitral regurgitation can provide significant benefits in terms of heart failure hospitalizations, survival, and quality of life when appropriate heart failure candidates with moderate to severe or severe mitral regurgitation while on optimal guideline-directed medical therapy can be identified. Key ingredients for success are preoperative evaluation and management and postoperative care by an interdisciplinary heart team. CONCLUSIONS: Given the discordance observed between trials, ongoing innovation in patient management, and potential expansion of indications for use, the evidence base must be expanded to optimize appropriate implementation of this complex therapy. This will require more complete capture of outcome data in real-world settings for all eligible candidates whether or not they receive this therapy. Inevitably, the indications for use of this therapy will expand, as will the devices and therapeutic approaches for this population, necessitating the study of comparative effectiveness through randomized trials or observational studies. Moreover, given the substantial variations in care delivery, conducting implementation research to delineate characteristics of the optimal care model would be of benefit.

Randomized Trials in Cardiac Surgery: JACC Review Topic of the Week.

Compared with randomized controlled trials (RCTs) in medical specialties, RCTs in cardiac surgery face specific issues. Individual and collective equipoise, rapid evolution of the surgical techniques, as well as difficulties in obtaining funding, and limited education in clinical epidemiology in the surgical community are among the most important challenges in the design phase of the trial. Use of complex interventions and learning curve effect, differences in individual operators' expertise, difficulties in blinding, and slow recruitment make the successful completion of cardiac surgery RCTs particularly challenging. In fact, over the course of the last 20 years, the number of cardiac surgery RCTs has declined significantly. In this review, a team of surgeons, trialists, and epidemiologists discusses the most important challenges faced by RCTs in cardiac surgery and provides a list of suggestions for the successful design and completion of cardiac surgery RCTs.

Cost-effectiveness of coronary artery bypass grafting plus mitral valve repair versus coronary artery bypass grafting alone for moderate ischemic mitral regurgitation.

OBJECTIVE: The Cardiothoracic Surgical Trials Network reported that left ventricular reverse remodeling at 2 years did not differ between patients with moderate ischemic mitral regurgitation randomized to coronary artery bypass grafting plus mitral valve repair (n = 150) or coronary artery bypass grafting alone (n = 151). To address health resource use implications, we compared costs and quality-adjusted survival. METHODS: We used individual patient data from the Cardiothoracic Surgical Trials Network trial on survival, hospitalizations, quality of life, and US hospitalization costs to estimate cumulative costs and quality-adjusted life years. A microsimulation model was developed to extrapolate to 10 years. Bootstrap and deterministic sensitivity analyses were performed to address uncertainty. RESULTS: In-hospital costs were $59,745 for coronary artery bypass grafting plus mitral valve repair versus $51,326 for coronary artery bypass grafting alone (difference $8419; 95% uncertainty interval, 2259-18,757). Two-year costs were $81,263 versus $67,341 (difference 13,922 [2370 to 28,888]), and quality-adjusted life years were 1.35 versus 1.30 (difference 0.05; -0.04 to 0.14), resulting in an incremental cost-effectiveness ratio of $308,343/quality-adjusted life year for coronary artery bypass grafting plus mitral valve repair. At 10 years, its costs remained higher ($107,733 vs $88,583, difference 19,150 [-3866 to 56,826]) and quality-adjusted life years showed no difference (-0.92 to 0.87), with 5.08 versus 5.08. The likelihood that coronary artery bypass grafting plus mitral valve repair would be considered cost-effective at 10 years based on a cost-effectiveness threshold of $100K/quality-adjusted life year did not exceed 37%. Only when this procedure reduces the death rate by a relative 5% will the incremental cost-effectiveness ratio fall below $100K/quality-adjusted life year. CONCLUSIONS: The addition of mitral valve repair to coronary artery bypass grafting for patients with moderate ischemic mitral regurgitation is unlikely to be cost-effective. Only if late mortality benefits can be demonstrated will it meet commonly used cost-effectiveness criteria.

Sex-Based Differences in Outcomes After Mitral Valve Surgery for Severe Ischemic Mitral Regurgitation: From the Cardiothoracic Surgical Trials Network.

OBJECTIVES: This study investigated sex-based differences in outcomes after mitral valve (MV) surgery for severe ischemic mitral regurgitation (SIMR). BACKGROUND: Whether differences in outcomes exist between men and women after surgery for SIMR remains unknown. METHODS: Patients enrolled in a randomized trial comparing MV replacement versus MV repair for SIMR were included and followed for 2 years. Endpoints for this analysis included all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE) (defined as the composite of death, stroke, hospitalization for heart failure, worsening New York Heart Association functional class or MV re-operation), quality of life (QOL), functional status, and percentage of change in left ventricular end-systolic volume index (LVESVI) from baseline through 2 years. RESULTS: Of 251 patients enrolled in the trial, 96 (38.2%) were women. Compared with men, women had smaller LV volumes and effective regurgitant orifice areas (EROA) but greater EROA/left ventricular (LV) end-diastolic volume ratios. At 2 years, women had higher rates of all-cause mortality (27.1% vs. 17.4%, respectively; adjusted hazard ratio [adjHR]: 1.85; 95% confidence interval [CI]: 1.05 to 3.26; p = 0.03) and of MACCE (49.0% vs. 38.1%, respectively; adjHR: 1.58; 95% CI: 1.06 to 2.37; p = 0.02). Women also reported worse QOL and functional status at 2 years. There were no significant differences in the percentage of change over 2 years in LVESVI between women and men (adjß: -10.4; 95% CI: -23.4 to 2.6; p = 0.12). CONCLUSIONS: Women with SIMR displayed different echocardiographic features and experienced higher mortality and worse QOL after MV surgery than men. There were no significant differences in the degree of reverse LV remodeling between sexes. (Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation [Severe Ischemic Mitral Regurgitation]; NCT00807040).

Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial.

Importance: Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery. Objective: To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant. Design, Setting, and Participants: A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018. Interventions: Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n = 106 vs n = 53). Main Outcomes and Measures: The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival. Results: Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P = .55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P = .80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P = .63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P = .68). Conclusions and Relevance: Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support. Trial Registration: clinicaltrials.gov Identifier: NCT02362646.

The Indigenous Faculty Forum: A Longitudinal Professional Development Program to Promote the Advancement of Indigenous Faculty in Academic Medicine.

American Indian, Alaska Native (AIAN) and Native Hawaiian and other Pacific Islander (NHPI) faculty, are substantially under-represented (<1%) at US medical schools. The Oregon Health & Science University's Northwest Native American Center of Excellence and The University of Hawai'i Native Hawaiian Center of Excellence have created an Indigenous Faculty Forum (IFF), a one-day structured course with flanking social activities, specifically designed to meet the unique needs of AIAN and NHPI academic faculty. It provided: (1) Indigenous space, (2) skill building, (3) networking, and (4) ongoing mentorship, each of which were included to specifically mitigate isolation and tokenism that negatively affects promotion and advancement. Two Forums have been conducted, first in Portland, OR in 2017 and the second in Hilo, Hawai'i in 2018. Nine of eighteen AIAN faculty in the three-state region (CA, OR, WA) attended IFF Session #1, representing 50% of known AIAN faculty in this region. Thirty-four Indigenous faculty from around the world attended IFF Session #2, with twenty-nine completing program evaluations. Respondents were predominantly female (81.6%), under age 44 (52.7%), and either instructors or assistant professors (52.6%). In terms of career choice, both sessions included primary care physicians as the most represented group (55.6% at Session #1 and 62.1% at Session #2). Increasing Indigenous faculty representation in US medical schools, while simultaneously fostering their career advancement and meaning in work, is vitally important. We have begun the work needed to address this problem and look forward to conducting more efforts, including longitudinal evaluation designs to study effectiveness.

Effect of Cerebral Embolic Protection Devices on CNS Infarction in Surgical Aortic Valve Replacement: A Randomized Clinical Trial.

Importance: Stroke is a major complication of surgical aortic valve replacement (SAVR). Objective: To determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic central nervous system (CNS) injury during SAVR. Design, Setting, and Participants: A randomized clinical trial of patients with calcific aortic stenosis undergoing SAVR at 18 North American centers between March 2015 and July 2016. The end of follow-up was December 2016. Interventions: Use of 1 of 2 cerebral embolic protection devices (n = 118 for suction-based extraction and n = 133 for intra-aortic filtration device) vs a standard aortic cannula (control; n = 132) at the time of SAVR. Main Outcomes and Measures: The primary end point was freedom from clinical or radiographic CNS infarction at 7 days (± 3 days) after the procedure. Secondary end points included a composite of mortality, clinical ischemic stroke, and acute kidney injury within 30 days after surgery; delirium; mortality; serious adverse events; and neurocognition. Results: Among 383 randomized patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), the rate of freedom from CNS infarction at 7 days was 32.0% with suction-based extraction vs 33.3% with control (between-group difference, -1.3%; 95% CI, -13.8% to 11.2%) and 25.6% with intra-aortic filtration vs 32.4% with control (between-group difference, -6.9%; 95% CI, -17.9% to 4.2%). The 30-day composite end point was not significantly different between suction-based extraction and control (21.4% vs 24.2%, respectively; between-group difference, -2.8% [95% CI, -13.5% to 7.9%]) nor between intra-aortic filtration and control (33.3% vs 23.7%; between-group difference, 9.7% [95% CI, -1.2% to 20.5%]). There were no significant differences in mortality (3.4% for suction-based extraction vs 1.7% for control; and 2.3% for intra-aortic filtration vs 1.5% for control) or clinical stroke (5.1% for suction-based extraction vs 5.8% for control; and 8.3% for intra-aortic filtration vs 6.1% for control). Delirium at postoperative day 7 was 6.3% for suction-based extraction vs 15.3% for control (between-group difference, -9.1%; 95% CI, -17.1% to -1.0%) and 8.1% for intra-aortic filtration vs 15.6% for control (between-group difference, -7.4%; 95% CI, -15.5% to 0.6%). Mortality and overall serious adverse events at 90 days were not significantly different across groups. Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; P = .02) and cardiac arrhythmias (57 vs 30; P = .004). Conclusions and Relevance: Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up. Trial Registration: clinicaltrials.gov Identifier: NCT02389894.

Pneumonia after cardiac surgery: Experience of the National Institutes of Health/Canadian Institutes of Health Research Cardiothoracic Surgical Trials Network.

RATIONALE: Pneumonia remains the most common major infection after cardiac surgery despite numerous preventive measures. OBJECTIVES: To prospectively examine the timing, pathogens, and risk factors, including modifiable management practices, for postoperative pneumonia and estimate its impact on clinical outcomes. METHODS: A total of 5158 adult cardiac surgery patients were enrolled prospectively in a cohort study across 10 centers. All infections were adjudicated by an independent committee. Competing risk models were used to assess the association of patient characteristics and management practices with pneumonia within 65 days of surgery. Mortality was assessed by Cox proportional hazards model and length of stay by a multistate model. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of pneumonia was 2.4%, 33% of which occurred after discharge. Older age, lower hemoglobin level, chronic obstructive pulmonary disease, steroid use, operative time, and left ventricular assist device/heart transplant were risk factors. Ventilation time (24-48 vs ≤24 hours; hazard ratio [HR], 2.83; 95% confidence interval [95% CI], 1.72-4.66; >48 hours HR, 4.67; 95% CI, 2.70-8.08), nasogastric tubes (HR, 1.80; 95% CI, 1.10-2.94), and each unit of blood cells transfused (HR, 1.16; 95% CI, 1.08-1.26) increased the risk of pneumonia. Prophylactic use of second-generation cephalosporins (HR, 0.66; 95% CI, 0.45-0.97) and platelet transfusions (HR, 0.49, 95% CI, 0.30-0.79) were protective. Pneumonia was associated with a marked increase in mortality (HR, 8.89; 95% CI, 5.02-15.75) and longer length of stay of 13.55 ± 1.95 days (bootstrap 95% CI, 10.31-16.58). CONCLUSIONS: Pneumonia continues to impose a major impact on the health of patients after cardiac surgery. After we adjusted for baseline risk, several specific management practices were associated with pneumonia, which offer targets for quality improvement and further research.

Hybrid Coronary Revascularization for the Treatment of Multivessel Coronary Artery Disease: A Multicenter Observational Study.

BACKGROUND: Hybrid coronary revascularization (HCR) combines minimally invasive surgical coronary artery bypass grafting of the left anterior descending artery with percutaneous coronary intervention (PCI) of non-left anterior descending vessels. HCR is increasingly used to treat multivessel coronary artery disease that includes stenoses in the proximal left anterior descending artery and at least 1 other vessel, but its effectiveness has not been rigorously evaluated. OBJECTIVES: This National Institutes of Health-funded, multicenter, observational study was conducted to explore the characteristics and outcomes of patients undergoing clinically indicated HCR and multivessel PCI for hybrid-eligible coronary artery disease, to inform the design of a confirmatory comparative effectiveness trial. METHODS: Over 18 months, 200 HCR and 98 multivessel PCI patients were enrolled at 11 sites. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) (i.e., death, stroke, myocardial infarction, repeat revascularization) within 12 months post-intervention. Cox proportional hazards models were used to model time to first MACCE event. Propensity scores were used to balance the groups. RESULTS: Mean age was 64.2 ± 11.5 years, 25.5% of patients were female, 38.6% were diabetic, and 4.7% had previous stroke. Thirty-eight percent had 3-vessel coronary artery disease, and the mean SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score was 19.7 ± 9.6. Adjusted for baseline risk, MACCE rates were similar between groups within 12 months post-intervention (hazard ratio [HR]: 1.063; p = 0.80) and during a median 17.6 months of follow-up (HR: 0.868; p = 0.53). CONCLUSIONS: These observational data from this first multicenter study of HCR suggest that there is no significant difference in MACCE rates over 12 months between patients treated with multivessel PCI or HCR, an emerging modality. A randomized trial with long-term outcomes is needed to definitively compare the effectiveness of these 2 revascularization strategies. (Hybrid Revascularization Observational Study; NCT01121263).

Rate Control versus Rhythm Control for Atrial Fibrillation after Cardiac Surgery.

BACKGROUND: Atrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitalizations. In patients with postoperative atrial fibrillation who are in stable condition, the best initial treatment strategy--heart-rate control or rhythm control--remains controversial. METHODS: Patients with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization, as assessed by the Wilcoxon rank-sum test. RESULTS: Postoperative atrial fibrillation occurred in 695 of the 2109 patients (33.0%) who were enrolled preoperatively; of these patients, 523 underwent randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P=0.76). There were no significant between-group differences in the rates of death (P=0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P=0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P=0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P=0.41). CONCLUSIONS: Strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02132767.).