Transcatheter Repair for Patients with Tricuspid Regurgitation.

BACKGROUND: Severe tricuspid regurgitation is a debilitating condition that is associated with substantial morbidity and often with poor quality of life. Decreasing tricuspid regurgitation may reduce symptoms and improve clinical outcomes in patients with this disease. METHODS: We conducted a prospective randomized trial of percutaneous tricuspid transcatheter edge-to-edge repair (TEER) for severe tricuspid regurgitation. Patients with symptomatic severe tricuspid regurgitation were enrolled at 65 centers in the United States, Canada, and Europe and were randomly assigned in a 1:1 ratio to receive either TEER or medical therapy (control). The primary end point was a hierarchical composite that included death from any cause or tricuspid-valve surgery; hospitalization for heart failure; and an improvement in quality of life as measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ), with an improvement defined as an increase of at least 15 points in the KCCQ score (range, 0 to 100, with higher scores indicating better quality of life) at the 1-year follow-up. The severity of tricuspid regurgitation and safety were also assessed. RESULTS: A total of 350 patients were enrolled; 175 were assigned to each group. The mean age of the patients was 78 years, and 54.9% were women. The results for the primary end point favored the TEER group (win ratio, 1.48; 95% confidence interval, 1.06 to 2.13; P = 0.02). The incidence of death or tricuspid-valve surgery and the rate of hospitalization for heart failure did not appear to differ between the groups. The KCCQ quality-of-life score changed by a mean (±SD) of 12.3±1.8 points in the TEER group, as compared with 0.6±1.8 points in the control group (P<0.001). At 30 days, 87.0% of the patients in the TEER group and 4.8% of those in the control group had tricuspid regurgitation of no greater than moderate severity (P<0.001). TEER was found to be safe; 98.3% of the patients who underwent the procedure were free from major adverse events at 30 days. CONCLUSIONS: Tricuspid TEER was safe for patients with severe tricuspid regurgitation, reduced the severity of tricuspid regurgitation, and was associated with an improvement in quality of life. (Funded by Abbott; TRILUMINATE Pivotal ClinicalTrials.gov number, NCT03904147.).

2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation" provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. METHODS: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" and the "2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.

Predictors and benefits of multiagent chemotherapy for pancreatic adenocarcinoma: Timing matters.

INTRODUCTION: Adjuvant (A) multiagent chemotherapy (MC) is the standard of care for patients with pancreatic adenocarcinoma (PDAC). Tolerating MC following a morbid operation may be difficult, thus neoadjuvant (NA) treatment is preferable. This study examined how the timing of chemotherapy was related to the regimen given and ultimately the overall survival (OS). METHODS: The National Cancer Database was queried from 2006 to 2017 for nonmetastatic PDAC patients who underwent surgical resection and received MC or single-agent chemotherapy (SC) pre- or postresection. Predictors of receiving MC were determined using multivariable logistic regression. Five-year OS was evaluated using the Kaplan-Meier and Cox proportional hazards model. RESULTS: A total of 12,440 patients (NA SC, n = 663; NA MC, n = 2313; A SC, n = 6152; A MC, n = 3312) were included. MC utilization increased from 2006-2010 to 2011-2017 (33.1%-49.7%; odds ratio [OR]: 0.59; p < 0.001). Younger age, fewer comorbidities, higher clinical stage, and larger tumor size were all associated with receipt of MC (all p < 0.001), but NA treatment was the greatest predictor (OR 5.18; 95% confidence interval [CI]: 4.63-5.80; p < 0.001). MC was associated with increased median 5-year OS (26.0 vs. 23.9 months; hazard ratio [HR]: 0.92; 95% CI: 0.88-0.96) and NA MC was associated with the highest survival (28.2 months) compared to NA SC (23.3 months), A SC (24.0 months), and A MC (24.6 months; p < 0.001). CONCLUSION: Use and timing of MC contribute to OS in PDAC with an improved 5-year OS compared to SC. The greatest predictor of receiving MC was being given as NA therapy and the greatest survival benefit was the NA MC subgroup. Randomized studies evaluating the timing of effective MC in PDAC are needed.

The benefit of adjuvant chemotherapy following pancreaticoduodenectomy for pancreatic adenocarcinoma depends on response to neoadjuvant therapy.

BACKGROUND: The benefit of adjuvant therapy (AT) remains unclear in pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and surgical resection. METHODS: The 2019 National Cancer Database was queried for patients with non-metastatic PDAC who received NAT followed by pancreaticoduodenectomy. Only patients with data regarding receipt of AT were included. Patients were classified if they had nodal down-staging specifically, or any downstaging (Tumor, Nodal, or overall). Propensity score matching (PSM) adjusted for pretreatment covariate imbalance between groups. The weighted Kaplan-Meier method and log-rank test were used to estimate the cumulative survival. RESULTS: After exclusion criteria and PSM, a total of 2784 patients remained; 1689 (60.7%) received AT and 1095 (39.3%) did not receive AT. Among all, those with additional AT had a significantly improved overall survival (OS) (p < 0.001). Upon evaluation of patients without downstaging after NAT, those who received AT had improved OS (no nodal downstaging or any downstaging; p = 0.002; p = 0.001). When evaluating patients with downstaging after NAT, those receiving AT did not have improved OS (nodal downstaging or any downstaging: p = 0.352; p = 0.99). CONCLUSION: Response to NAT appears to correlate with the benefit of AT following pancreaticoduodenectomy; patients who have a favorable response to NAT may not benefit from AT.

Upadacitinib as Rescue Therapy for the Treatment of Acute Severe Colitis in an Acute Care Setting.

BACKGROUND: Inflammatory bowel disease is a chronic, relapsing, and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy. AIMS: We hypothesized that upadacitinib may be effective in treating acute severe colitis. METHODS: A retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy was performed. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. RESULTS: Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Most patients who did not undergo surgery were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores. CONCLUSION: Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.

Divergent clinical outcomes in a phase 2B trial of the TLPLDC vaccine in preventing melanoma recurrence and the impact of dendritic cell collection methodology: a randomized clinical trial.

BACKGROUND: A randomized, double-blind, placebo-controlled phase 2b trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine was conducted in patients with resected stage III/IV melanoma. Dendritic cells (DCs) were harvested with and without granulocyte-colony stimulating factor (G-CSF). This analysis investigates differences in clinical outcomes and RNA gene expression between DC harvest methods. METHODS: The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles (YCWPs) and exposing them to phagocytosis by DCs. For DC harvest, patients had a direct blood draw or were pretreated with G-CSF before blood draw. Patients were randomized 2:1 to receive TLPLDC or placebo. Differences in disease-free survival (DFS) and overall survival (OS) were evaluated. RNA-seq analysis was performed on the total RNA of TLPLDC + G and TLPLDC vaccines to compare gene expression between groups. RESULTS: 144 patients were randomized: 103 TLPLDC (47 TLPLDC/56 TLPLDC + G) and 41 placebo (19 placebo/22 placebo + G). Median follow-up was 27.0 months. Both 36-month DFS (55.8% vs. 24.4% vs. 30.0%, p = 0.010) and OS (94.2% vs. 69.8% vs. 70.9%, p = 0.024) were improved in TLPLDC compared to TLPLDC + G or placebo, respectively. When compared to TLPLDC + G vaccine, RNA-seq from TLPLDC vaccine showed upregulation of genes associated with DC maturation and downregulation of genes associated with DC suppression or immaturity. CONCLUSIONS: Patients receiving TLPLDC vaccine without G-CSF had improved OS and DFS. Outcomes remained similar between patients receiving TLPLDC + G and placebo. Direct DC harvest without G-CSF had higher expression of genes linked to DC maturation, likely improving clinical efficacy.

Assessment of Beat-To-Beat Variability in Left Atrial Hemodynamics Using Real Time Phase Contrast MRI in Patients With Atrial Fibrillation.

BACKGROUND: Hemodynamic assessment of left atrial (LA) flow using phase contrast MRI provides insight into thromboembolic risk in atrial fibrillation (AF). However, conventional flow imaging techniques are averaged over many heartbeats. PURPOSE: To evaluate beat-to-beat variability and LA hemodynamics in patients with AF using real time phase contrast (RTPC) MRI. STUDY TYPE: Prospective. SUBJECTS: Thirty-five patients with history of AF (68 ± 10 years, nine female), 10 healthy controls (57 ± 19 years, four female). FIELD STRENGTH/SEQUENCE: 5T, 2D RTPC with through-plane velocity-encoded gradient echo sequence and 4D flow MRI with three-directional velocity-encoded gradient echo sequence. ASSESSMENT: RTPC was continuously acquired for a mid-LA slice in all subjects. 4D flow data were interpolated at the RTPC location and normally projected for comparison with RTPC. RR intervals extracted from RTPC were used to calculate heart rate variability (HRV = interquartile range over median × 100%). Patients were classified into low (<9.7%) and high (>9.7%) HRV groups. LA peak/mean velocity and stasis (%velocities < 5.8 cm/sec) were calculated from segmented 2D images. Variability in RTPC flow metrics was quantified by coefficient of variation (CV) over all cycles. STATISTICAL TESTS: Pearson's correlation coefficient (r), Bland-Altman analysis, Kruskal-Wallis test. A P value < 0.05 was considered statistically significant. RESULTS: RTPC and 4D flow measurements were strongly/significantly correlated for all hemodynamic parameters (R2  = 0.75-0.83) in controls. Twenty-four patients had low HRV (mean = 4 ± 2%) and 11 patients had high HRV (27 ± 9%). In patients, increased HRV was significantly correlated with CV of peak velocity (r = 0.67), mean velocity (r = 0.51), and stasis (r = 0.41). A stepwise decrease in peak/mean velocity and increase in stasis was observed when comparing controls vs. low HRV vs. high HRV groups. Mean velocity and stasis differences were significant for control vs. high HRV groups. CONCLUSIONS: RTPC may be suitable for assessing the impact of HRV on hemodynamics and provide insight for AF management in highly arrhythmic patients. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Global Aortic Pulse Wave Velocity is Unchanged in Bicuspid Aortopathy With Normal Valve Function but Elevated in Patients With Aortic Valve Stenosis: Insights From a 4D Flow MRI Study of 597 Subjects.

BACKGROUND: Aortopathy is common with bicuspid aortic valve (BAV), and underlying intrinsic tissue abnormalities are believed causative. Valve-mediated hemodynamics are altered in BAV and may contribute to aortopathy and its progression. The contribution of intrinsic tissue defects versus altered hemodynamics to aortopathy progression is not known. PURPOSE: To investigate relative contributions of tissue-innate versus hemodynamics in progression of BAV aortopathy. STUDY TYPE: Retrospective. SUBJECTS: Four hundred seventy-three patients with aortic dilatation (diameter ≥40 mm; comprised of 281 BAV with varied AS severity, 192 tricuspid aortic valve [TAV] without AS) and 124 healthy controls. Subjects were 19-91 years (141/24% female). FIELD STRENGTH/SEQUENCE: 1.5T, 3T; time-resolved gradient-echo 3D phase-contrast (4D flow) MRI. ASSESSMENT: A surrogate measure for global aortic wall stiffness, pulse wave velocity (PWV), was quantified from MRI by standardized, automated technique based on through-plane flow cross-correlation maximization. Comparisons were made between BAV patients with aortic dilatation and varying aortic valve stenosis (AS) severity and healthy subjects and aortopathy patients with normal TAV. STATISTICAL TESTS: Multivariable regression, analysis of covariance (ANCOVA), Tukey's, student's (t), Mann-Whitney (U) tests, were used with significance levels P < 0.05 or P < 0.01 for post-hoc Bonferroni-corrected t/U tests. Bland-Altman and ICC calculations were performed. RESULTS: Multivariable regression showed age with the most significant association for increased PWV in all groups (increase 0.073-0.156 m/sec/year, R2  = 0.30-48). No significant differences in aortic PWV were observed between groups without AS (P = 0.20-0.99), nor were associations between PWV and regurgitation or Sievers type observed (P = 0.60, 0.31 respectively). In contrast, BAV AS patients demonstrated elevated PWV and a significant relationship for AS severity with increased PWV (covariate: age, R2  = 0.48). BAV and TAV patients showed no association between aortic diameter and PWV (P = 0.73). DATA CONCLUSION: No significant PWV differences were observed between BAV patients with normal valve function and control groups. However, AS severity and age in BAV patients were directly associated with PWV increases. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Testing and Evaluation of a Novel Hemostatic Matrix in a Swine Junctional Hemorrhage Model.

INTRODUCTION: In an ongoing effort to improve survival and reduce blood loss from hemorrhagic injuries on the battlefield, new hemostatic dressings continue to be developed. This study aimed to determine the efficacy of a novel silicon dioxide-based hemostatic matrix (HM) and compare it with the current military standard Quikclot Combat Gauze (QCG) utilizing a lethal femoral artery injury model. MATERIALS AND METHODS: The femoral arteries of 20 anesthetized swine were isolated, and an arteriotomy was performed. After a 45 s free bleed, the wound was treated with either HM or QCG (n = 10 per group). Following a 60-min observation period, ipsilateral leg manipulations and angiography were performed. Animal survival, hemostasis, blood loss, exothermic reaction, and femoral artery patency were analyzed. RESULTS: Despite a volumetric size discrepancy between the two products tested, the survival rate was similar between the two groups (80% HM, 90% QCG, n = 10, P = 0.588). Immediate hemostasis was obtained in 50% of HM animals and 40% of QCG animals. There was no difference in total blood loss recorded between the two groups (P = 0.472). Femoral artery patency rates following ipsilateral leg manipulations were similar between the two groups (50% HM, 33% QCG, P = 0.637), with no contrast extravasation in HM-treated wounds (0% HM, 33% QCG, P = 0.206). There was no significant difference in either pretreatment or posttreatment laboratory values, and there were no exothermic reactions in either group. CONCLUSIONS: The SiOxMed HM demonstrated comparable hemostatic efficacy to QCG. The tested form of HM may be appropriate for surgical or topical hemostasis applications, and with further product development, it could be used for battlefield trauma implementation.

Systolic reverse flow derived from 4D flow cardiovascular magnetic resonance in bicuspid aortic valve is associated with aortic dilation and aortic valve stenosis: a cross sectional study in 655 subjects.

BACKGROUND: Bicuspid aortic valve (BAV) disease is associated with increased risk of aortopathy. In addition to current intervention guidelines, BAV mediated changes in aortic 3D hemodynamics have been considered as risk stratification measures. We aimed to evaluate the association of 4D flow cardiovascular magnetic resonance (CMR) derived voxel-wise aortic reverse flow with aortic dilation and to investigate the role of aortic valve regurgitation (AR) and stenosis (AS) on reverse flow in systole and diastole. METHODS: 510 patients with BAV (52 ± 14 years) and 120 patients with trileaflet aortic valve (TAV) (61 ± 11 years) and mid-ascending aorta diameter (MAAD) > 35 mm who underwent CMR including 4D flow CMR were retrospectively included. An age and sex-matched healthy control cohort (n = 25, 49 ± 12 years) was selected. Voxel-wise reverse flow was calculated in the aorta and quantified by the mean reverse flow in the ascending aorta (AAo) during systole and diastole. RESULTS: BAV patients without AS and AR demonstrated significantly increased systolic and diastolic reverse flow (222% and 13% increases respectively, p < 0.01) compared to healthy controls and also had significantly increased systolic reverse flow compared to TAV patients with aortic dilation (79% increase, p < 0.01). In patients with isolated AR, systolic and diastolic AAo reverse flow increased significantly with AR severity (c = - 83.2 and c = - 205.6, p < 0.001). In patients with isolated AS, AS severity was associated with an increase in both systolic (c = - 253.1, p < 0.001) and diastolic (c = - 87.0, p = 0.02) AAo reverse flow. Right and left/right and non-coronary fusion phenotype showed elevated systolic reverse flow (> 17% increase, p < 0.01). Right and non-coronary fusion phenotype showed decreased diastolic reverse flow (> 27% decrease, p < 0.01). MAAD was an independent predictor of systolic (p < 0.001), but not diastolic, reverse flow (p > 0.1). CONCLUSION: 4D flow CMR derived reverse flow associated with BAV was successfully captured even in the absence of AR or AS and in comparison to TAV patients with aortic dilation. Diastolic AAo reverse flow increased with AR severity while AS severity strongly correlated with increased systolic reverse flow in the AAo. Additionally, increasing MAAD was independently associated with increasing systolic AAo reverse flow. Thus, systolic AAo reverse flow may be a valuable metric for evaluating disease severity in future longitudinal outcome studies.

Immunologic and dose dependent effects of rapamycin and its evolving role in chemoprevention.

Rapamycin inhibits the mechanistic (formally mammalian) target of rapamycin (mTOR), an evolutionarily conserved intracellular kinase that influences activation of growth signaling pathways and immune responses to malignancy. Rapamycin has been found to have both immunosuppressant and immunostimulatory effects throughout the innate and adaptive responses based on the inhibition of mTOR signaling. While the immunosuppressant properties of rapamycin and mTOR inhibition explain rapamycin's success in the prevention of transplant rejection, the immunostimulatory characteristics are likely partially responsible for rapamycin's anti-neoplastic effects. The immunologic response to rapamycin is at least partially dependent on the dose and administration schedule, with lower doses inducing immunostimulation and intermittent dosing promoting immune function while limiting metabolic and immunosuppressant toxicities. In addition to its FDA-approved application in advanced malignancies, rapamycin may be effective as a chemopreventive agent, suspending progression of low-grade cancers, preventing invasive conversion of in situ malignancy, or delaying malignant transformation of established pre-malignant conditions.

Tricuspid valve disease prevalence and the impact of tricuspid valve surgery on cardiovascular events and hospital resource use in medicare beneficiaries.

BACKGROUND: Tricuspid valve disease (TVD) is presumed common, however, little is known about its prevalence or the impact of tricuspid valve surgery (TVS) on healthcare resource use. METHODS: To describe the prevalence of TVD and assess the impact of TVS on resource utilization, Medicare Fee-For-Service beneficiaries from 2011 -2019 were assessed for the prevalence of non-rheumatic TVD. Hospital costs and rates of all-cause, cardiovascular (CV), and heart failure (HF) hospitalizations were compared in the 3 months pre TVS to acute (0-3 months) and chronic (3 -12 months) post TVS periods. RESULTS: Among 80.3 million beneficiaries from 2011 - 2019 Q1, over 700,000 (0.9%) had non-rheumatic TVD with 1.4% undergoing TVS. Thirty-day and 1 year mortality after TVS was 5.5% to15.5%. Compared with pre-surgery, CV and HF hospitalizations decreased from 0.12 to 0.08 per patient-month (P <.001), and 0.06 to 0.04 (P <.001) acutely. All-cause hospitalizations increased from 0.18 per patient-month to 0.23 per patient-month acutely post-surgery (P <.001), before decreasing to 0.09 per patient-month chronically (P <.001). Hospital costs increased from $2,174 per patient-month to $4,171 per patient-month acutely (P < .001), before falling to $1,441 per patient-month (P < .001) chronically. Lower costs for HF and CV hospitalization in both acute (P = .028 and P < .001, respectively) and chronic (P < .001 for both) periods were observed. CONCLUSIONS: TVS is associated with reduced CV and HF hospitalizations and associated hospital costs. Future work should determine whether transcatheter tricuspid valve repair offers similar or additional benefits.

Deep learning-based velocity antialiasing of 4D-flow MRI.

PURPOSE: To develop a convolutional neural network (CNN) for the robust and fast correction of velocity aliasing in 4D-flow MRI. METHODS: This study included 667 adult subjects with aortic 4D-flow MRI data with existing velocity aliasing (n = 362) and no velocity aliasing (n = 305). Additionally, 10 controls received back-to-back 4D-flow scans with systemically varied velocity-encoding sensitivity (vencs) at 60, 100, and 175 cm/s. The no-aliasing data sets were used to simulate velocity aliasing by reducing the venc to 40%-70% of the original, alongside a ground truth locating all aliased voxels (153 training, 152 testing). The 152 simulated and 362 existing aliasing data sets were used for testing and compared with a conventional velocity antialiasing algorithm. Dice scores were calculated to quantify CNN performance. For controls, the venc 175-cm/s scans were used as the ground truth and compared with the CNN-corrected venc 60 and 100 cm/s data sets RESULTS: The CNN required 176 ± 30 s to perform compared with 162 ± 14 s for the conventional algorithm. The CNN showed excellent performance for the simulated data compared with the conventional algorithm (median range of Dice scores CNN: [0.89-0.99], conventional algorithm: [0.84-0.94], p < 0.001, across all simulated vencs) and detected more aliased voxels in existing velocity aliasing data sets (median detected CNN: 159 voxels [31-605], conventional algorithm: 65 [7-417], p < 0.001). For controls, the CNN showed Dice scores of 0.98 [0.95-0.99] and 0.96 [0.87-0.99] for venc = 60 cm/s and 100 cm/s, respectively, while flow comparisons showed moderate-excellent agreement. CONCLUSION: Deep learning enabled fast and robust velocity anti-aliasing in 4D-flow MRI.

Downstaging of Pancreatic Adenocarcinoma With Either Neoadjuvant Chemotherapy or Chemoradiotherapy Improves Survival.

BACKGROUND: Neoadjuvant chemotherapy (NAC) or chemoradiation (NAC+XRT) is incorporated into the treatment of localized pancreatic adenocarcinoma (PDAC), often with the goal of downstaging before resection. However, the effect of downstaging on overall survival, particularly the differential effects of NAC and NAC+XRT, remains undefined. This study examined the impact of downstaging from NAC and NAC+XRT on overall survival. METHODS: The National Cancer Data Base (NCDB) was queried from 2006 to 2015 for patients with non-metastatic PDAC who received NAC or NAC+XRT. Rates of overall and nodal downstaging, and pathologic complete response (pCR) were assessed. Predictors of downstaging were evaluated using multivariable logistic regression. Overall survival (OS) was assessed with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: The study enrolled 2475 patients (975 NAC and 1500 NAC+XRT patients). Compared with NAC, NAC+XRT was associated with higher rates of overall downstaging (38.3 % vs 23.6 %; p ≤ 0.001), nodal downstaging (16.0 % vs 7.8 %; p ≤ 0.001), and pCR (1.7 % vs 0.7 %; p = 0.041). Receipt of NAC+XRT was independently predictive of overall (odds ratio [OR] 2.28; p < 0.001) and nodal (OR 3.09; p < 0.001) downstaging. Downstaging by either method was associated with improved 5-year OS (30.5 vs 25.2 months; p ≤ 0.001). Downstaging with NAC was associated with an 8-month increase in median OS (33.7 vs 25.6 months; p = 0.005), and downstaging by NAC+XRT was associated with a 5-month increase in median OS (30.0 vs 25.0 months; p = 0.008). Cox regression showed an association of overall downstaging with an 18 % reduction in the risk of death (hazard ratio [HR] 0.82; 95 % confidence interval, 0.71-0.95; p = 0.01) CONCLUSION: Downstaging after neoadjuvant therapies improves survival. The addition of radiation therapy may increase the rate of downstaging without affecting overall oncologic outcomes.

Staged hybrid totally thoracoscopic maze and catheter ablation for atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a growing health problem and is associated with increased risk of stroke. The Cox-Maze surgical procedure has offered the highest success rate, but utilization of this technique is low due to procedure invasiveness and complexity. Advances in catheter ablation and minimally invasive surgical techniques offer new options for AF treatment. METHODS: In this review, we describe current trends and outcomes of minimally invasive treatment of persistent and long-standing persistent AF. RESULTS: Treatment of persistent and long-standing persistent AF can be successfully treated using a team approach combining cardiac surgery and electrophysiology procedures. With this approach, the 1-year freedom from AF off antiarrhythmic drugs was 85%. DISCUSSION: There are a variety of techniques and approaches used around the world as technology evolves to help develop new treatment strategies for AF. Our report will focus on a hybrid treatment approach using surgical and electrophysiology approaches providing enhanced treatment options by replicating Cox-Maze IV lesions using skills from each specialty. Closure of the left atrial appendage as part of these procedures enhances protection from late stroke. A team approach provides a cohesive evaluation, treatment, and monitoring plan for patients. Development of successful, less invasive treatment options will help address the growing population of patients with AF.

A history of collaboration between electrophysiologists and arrhythmia surgeons.

INTRODUCTION: The notion that medically-refractory arrhythmias might one day be amenable to interventional therapy slowly began to appear in the early 1960's. At that time, there were no "interventional electrophysiologists" or "arrhythmia surgeons" and there was little appreciation of the relationship between anatomy and electrophysiology outside the heart's specialized conduction system. METHODS: In this review, we describe the evolution of collaboration between electrophysiologists and surgeons. RESULTS: Although accessory atrio-ventricular (AV) connections were first identified in 1893 and the Wolff-Parkinson-White (WPW) syndrome was described 37 years later (1930), it was another 37 years (1967) before those anatomic AV connections were proven to be responsible for the clinical syndrome. The success of the subsequent surgical procedures for the WPW syndrome, AV node reentry tachycardia, automatic atrial tachycardias, ischemic and non-ischemic ventricular tachycardias and atrial fibrillation over the next two decades depended on a close, sometimes daily, collaboration between electrophysiologists and surgeons. In the past two decades, that tight collaboration was largely abandoned until the recent introduction of "hybrid procedures" for the treatment of atrial fibrillation. CONCLUSIONS: A retrospective assessment of the 50 years of interventional therapy for arrhythmias clearly demonstrates the clinical benefits of a close collaboration between electrophysiologists and arrhythmia surgeons, regardless of which one is actually performing the intervention.

Valve-sparing versus valve-replacing aortic root replacement in patients with aortic root aneurysm.

BACKGROUND: Valve-sparing aortic root replacement (VSARR) is an alternative to valve-replacing aortic root replacement (VRARR) with valved-conduits based on recent guidelines for clinical practice. This study investigated outcomes of these two procedures in patients with nonstenotic valves. METHODS: Between January 7, 2007 and June 30, 2019, 475 patients with aortic root aneurysm without aortic stenosis underwent VSARR (151) or VRARR (324) techniques. Propensity score-matching (PSM) was used to alleviate confounding. Endpoints were 30-day mortality, 8-year survival and reoperation, aortic regurgitation, and valve gradients. RESULTS: PSM created 69 pairs of patients with a mean age 52 ± 13 years (10.1% Marfan syndrome, 34.8% bicuspid aortic valve). There was no statistically significant difference in major perioperative morbidity or 30-day mortality (0% VSARR vs. 1.4% VRARR; p = 0.316). Overall survival was significantly higher (p = 0.025) in the VSARR group versus the VRARR group (8-year estimates 100% vs. 88.9%, respectively), while freedom from valve reoperation was similar (p = 0.97, 8-year estimates 90.9% vs. 96.7%, respectively). Freedom from > moderate-severe AR was not significantly different (p = 0.08, 8-year estimates 90.0% VSARR group vs. 100% VRARR), but mean valve gradients at last follow-up were better in the VSARR group (5.9 vs. 13.2 mmHg, p < 0.001). CONCLUSIONS: VSARR is a safe operation in patients with aortic root aneurysm and nonstenotic aortic valves in the hands of experienced surgeons. Freedom from reoperation is similar and the mode of aortic valve failure differs between the two groups.

Subgroup analysis of nelipepimut-S plus GM-CSF combined with trastuzumab versus trastuzumab alone to prevent recurrences in patients with high-risk, HER2 low-expressing breast cancer.

HER2-targeted therapy has not benefited patients with low levels of HER2 expression; however, combination therapy may be effective. Primary analysis of a phase IIb trial investigating the HER2-derived vaccine nelipepimut-S (NPS) did not benefit the intention-to-treat population, but subset analysis showed a benefit in triple-negative breast cancer (TNBC) patients. The subset analysis of this multicenter, randomized, single-blind, phase IIb trial identified significant improvement in 36-month disease-free survival (DFS) between NPS (n = 55) and placebo (n = 44) in TNBC (HR 0.25, p = 0.01) and those who express HLA-A24 (HR 0.41, p = 0.05). The TNBC cohort demonstrated improved 36-month DFS in those with HER2 1+ expression (HR 0.17, p = 0.01), HLA-A24 positivity (HR 0.08, p < 0.01), or in those who received neoadjuvant chemotherapy (HR 0.21, p < 0.01). NPS vaccination with trastuzumab was associated with improved 36-month DFS among patients with TNBC. The observed benefit to this high-risk subgroup warrants confirmation in a phase III trial.

4D Flow with MRI.

Magnetic resonance imaging (MRI) has become an important tool for the clinical evaluation of patients with cardiac and vascular diseases. Since its introduction in the late 1980s, quantitative flow imaging with MRI has become a routine part of standard-of-care cardiothoracic and vascular MRI for the assessment of pathological changes in blood flow in patients with cardiovascular disease. More recently, time-resolved flow imaging with velocity encoding along all three flow directions and three-dimensional (3D) anatomic coverage (4D flow MRI) has been developed and applied to enable comprehensive 3D visualization and quantification of hemodynamics throughout the human circulatory system. This article provides an overview of the use of 4D flow applications in different cardiac and vascular regions in the human circulatory system, with a focus on using 4D flow MRI in cardiothoracic and cerebrovascular diseases.

Concomitant treatment of atrial fibrillation during mitral valve surgery.

INTRODUCTION: Surgical management of atrial fibrillation (AF) is a well-established method of preventing complications and late mortality in patients presenting with AF before mitral valve (MV) surgery. However, despite a substantial body of evidence and a Class I recommendation to apply surgical ablation (SA) concomitant to MV surgery, the utilization of SA remains low. METHODS: In this study, we sought to summarize the current trends in the SA of AF during MV surgery and update the medical community on its advantages, including perioperative mortality and morbidity, freedom from AF, as well as long-term survival and stroke rates. RESULTS: The data indicate that SA can be added with no increased risk (and perhaps a reduction in perioperative risk) and improved late survival compared to patients with AF left untreated during MV surgery. DISCUSSION: Inconsistent application of SA may be related to inaccurate perceptions regarding the complexity of the procedure itself, extended cross-clamp and bypass times with attendant increased risks, views that it is ineffective, and increased need for an early pacemaker. CONCLUSION: Education in the proper performance of SA, including careful placement of the lesions and attainment of the full transmural effect, contributes to procedure success. Propagating the safety and positive outcomes may also address the concerns.