Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest Trial (GOT ICE): A Randomized Clinical Trial Comparing Outcomes After Aortic Arch Surgery.

BACKGROUND: Deep hypothermia has been the standard for hypothermic circulatory arrest (HCA) during aortic arch surgery. However, centers worldwide have shifted toward lesser hypothermia with antegrade cerebral perfusion. This has been supported by retrospective data, but there has yet to be a multicenter, prospective randomized study comparing deep versus moderate hypothermia during HCA. METHODS: This was a randomized single-blind trial (GOT ICE [Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest]) of patients undergoing arch surgery with HCA plus antegrade cerebral perfusion at 4 US referral aortic centers (August 2016-December 2021). Patients were randomized to 1 of 3 hypothermia groups: DP, deep (≤20.0 °C); LM, low-moderate (20.1-24.0 °C); and HM, high-moderate (24.1-28.0 °C). The primary outcome was composite global cognitive change score between baseline and 4 weeks postoperatively. Analysis followed the intention-to-treat principle to evaluate if: (1) LM noninferior to DP on global cognitive change score; (2) DP superior to HM. The secondary outcomes were domain-specific cognitive change scores, neuroimaging findings, quality of life, and adverse events. RESULTS: A total of 308 patients consented; 282 met inclusion and were randomized. A total of 273 completed surgery, and 251 completed the 4-week follow-up (DP, 85 [34%]; LM, 80 [34%]; HM, 86 [34%]). Mean global cognitive change score from baseline to 4 weeks in the LM group was noninferior to the DP group; likewise, no significant difference was observed between DP and HM. Noninferiority of LM versus DP, and lack of difference between DP and HM, remained for domain-specific cognitive change scores, except structured verbal memory, with noninferiority of LM versus DP not established and structured verbal memory better preserved in DP versus HM (P = 0.036). There were no significant differences in structural or functional magnetic resonance imaging brain imaging between groups postoperatively. Regardless of temperature, patients who underwent HCA demonstrated significant reductions in cerebral gray matter volume, cortical thickness, and regional brain functional connectivity. Thirty-day in-hospital mortality, major morbidity, and quality of life were not different between groups. CONCLUSIONS: This randomized multicenter study evaluating arch surgery HCA temperature strategies found low-moderate hypothermia noninferior to traditional deep hypothermia on global cognitive change 4 weeks after surgery, although in secondary analysis, structured verbal memory was better preserved in the deep group. The verbal memory differences in the low- and high-moderate groups and structural and functional connectivity reductions from baseline merit further investigation and suggest opportunities to further optimize brain perfusion during HCA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02834065.

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. Structure: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.

The Impact of MOMENTUM 3 Trial Eligibility on Left Ventricular Assist Device Outcomes: A Real-World Experience.

INTRODUCTION: Although the landmark MOMENTUM 3 trial was associated with excellent short-term left ventricular assist device (LVAD) outcomes, many end-stage heart failure patients would not have met the trial eligibility criteria. Moreover, the outcomes of trial ineligible patients are poorly characterized. Therefore, we undertook this study to compare MOMENTUM 3 eligible and ineligible patients. METHODS: We conducted a retrospective review of all primary LVAD implants from 2017 to 2022. Primary stratification was according to MOMENTUM 3 inclusion and exclusion criteria. Primary outcome was survival. Secondary outcomes included complications and length of stay. Multivariable Cox proportional hazards regression models were constructed to further characterize outcomes. RESULTS: From 2017 to 2022, 96 patients underwent primary LVAD implantation. Thirty-seven (38.54%) patients were trial eligible while 59 (61.46%) were ineligible. When stratified by trial eligibility, patients who were trial eligible had higher 1-year (80.15% versus 94.52%, P = 0.04) and 2-year survival (70.17% versus 94.52%, P = 0.02). Multivariable analysis showed that trial eligibility was protective of mortality at both 1 y (HR: 0.19 [0.04-0.99], P = 0.049) and 2 y (HR: 0.17 [0.03-0.81], P = 0.03). Although the groups had similar rates of bleeding, stroke, and right ventricular failure, trial ineligibility was associated with a longer periprocedural length of stay. CONCLUSIONS: In conclusion, the majority of contemporary LVAD patients would not have been eligible for the MOMENTUM 3 trial. Ineligible patients have decreased but acceptable short-term survival. Our findings suggest that a simply reductionist approach to short-term mortality may improve outcomes but fail to capture the majority of patients who could benefit from therapy.

Novel Estimates of Renal Function are Associated with Short-Term Left Ventricular Assist Device Outcomes.

INTRODUCTION: Although preoperative kidney function has been associated with left ventricular assist device (LVAD) outcomes, most previous estimates of glomerular filtration rates (eGFRs) have utilized race in the calculation. Recently, novel eGFR equations independent of race have been suggested and validated. Therefore, we undertook this study to evaluate the predictive value of a novel, non-race-based eGFR calculation on short-term LVAD outcomes. METHODS: We conducted a retrospective review of all primary LVAD implants from 2017 to 2022 at our institution. eGFR was calculated using the novel Chronic Kidney Disease Epidemiology Collaboration 2021 formula (CKD-EPI 2021). eGFR was also calculated according to the Modification of Diet in Renal Disease equation for historical reference. Primary stratification was by eGFR: ≥60, 30-60, and <30. The primary outcome was 1-y survival. Multivariable Cox proportional hazards regression modeling was used to further evaluate the impact of kidney function on 1-y mortality. RESULTS: From 2017 to 2022, 91 patients underwent LVAD implantation with a HeartMate 3 device. The average age was 65.20 ± 11.08, 77 (84.62%) were male, and 14 (15.38%) were Black. The mean CKD-EPI 2021 eGFR was 56.07 ± 23.55 compared with 54.72 ± 26.37 as calculated by Modification of Diet in Renal Disease (P = 0.719). Overall, 30-d and 1-y survival was 96.7% and 85.0%, respectively. When stratified by eGFR, there was a significant difference in 1-y survival (≥60, 93.46%; 30-60, 87.36%; <30, 62.75%; P = 0.016). On multivariable analysis, a preoperative eGFR <30 was associated with an increased hazard of 1-y mortality (5.58 [1.06-29.17], P = 0.043). CONCLUSIONS: In conclusion, non-race-based estimates of renal function are predictive of short-term LVAD outcomes. Further investigation of this phenomenon is warranted.

Temporary Right Ventricular Assist Device Support for Acute Right Heart Failure: A Single-Center Experience.

INTRODUCTION: Severe right ventricular (RV) failure is associated with significant morbidity and mortality. Although right ventricular assist devices (RVADs) are increasingly used for refractory RV failure, there is limited data on their short- and long-term outcomes. Therefore, we undertook this study to better understand our experience with temporary RVADs. METHODS: We conducted a retrospective review of all RVADS performed from 2017 to 2021. Patients supported with surgical RVADs, the Protek Duo device, and the Impella RP device were included. Patients were stratified by the type of RVAD and by etiology of RV failure. Survival was assessed by the Kaplan-Meier method and multivariable Cox proportional hazards regression models. RESULTS: From 2017 to 2021, 42 patients underwent RVAD implantation: 32 with a Protek Duo, 6 with an Impella RP, and 4 with a surgical RVAD. Majority of patients were already supported with an alternate form of mechanical support. Most patients had impaired renal function, decreased hepatic function, and lactic acidosis at the time of cannulation. The median duration of RVAD support was 8.5 [5-19] d. Survival to decannulation was 68.4%, to discharge was 47.4%, and to 1-y was 40.2%. Multivariable analysis identified elevated total bilirubin levels to be associated with 30-d mortality while increased hemoglobin levels were protective. After RVAD cannulation, the median number of pressors and inotropes was lower (P < 0.01) and the lactic acidosis was less (P < 0.01). CONCLUSIONS: In conclusion, RVAD support is associated with lower lactate levels, and decreased number of vasoactive medications, but is associated with significant morbidity and mortality.

Contemporary Outcomes of Isolated Tricuspid Valve Surgery.

INTRODUCTION: Isolated tricuspid valve (TV) surgery is uncommonly performed and has historically been associated with excessive operative mortality. We previously reported improved short-term outcomes at our center. Understanding contemporary outcomes of isolated TV surgery beyond the perioperative period is essential to properly benchmark outcomes of newer transcatheter interventions. METHODS: Patients who underwent isolated TV surgery from 2007 to 2021 at a single institution were retrospectively reviewed. Survival was estimated using the Kaplan-Meier method and multivariable Cox proportional hazards regression modeling identified independent risk factors for all-cause mortality. RESULTS: Among 173 patients undergoing isolated TV surgery, 103 (60%) underwent TV repair and 70 (40%) underwent TV replacement. Mean age was 60.3 ± 18.9 y and 55 (32%) were male. The most common etiology of TV disease was functional (46%). In-hospital mortality was 4.1% (7/173), with no difference between TV repair and replacement (P = 0.06). Overall survival at 1 y and 5 y was 78.3% (111/142) and 64.5% (53/82), respectively. After median (interquartile range) follow-up of 2.0 (0.6-4.4) y, patients undergoing TV repair experienced a higher unadjusted survival as compared to those undergoing TV replacement (log-rank P = 0.02). However, after adjusting for covariates, TV replacement was not an independent predictor of all-cause mortality (hazard ratio 1.40; 95% confidence interval, 0.71-2.76; P = 0.33). CONCLUSIONS: Isolated TV surgery can be performed with lower operative mortality than historically reported. Establishing survival benchmarks from TV surgery is important in the era of developing transcatheter interventions.

Anti-Granulocyte-Macrophage Colony-Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-controlled Trial.

Rationale: GM-CSF (granulocyte-macrophage colony-stimulating factor) has emerged as a promising target against the hyperactive host immune response associated with coronavirus disease (COVID-19). Objectives: We sought to investigate the efficacy and safety of gimsilumab, an anti-GM-CSF monoclonal antibody, for the treatment of hospitalized patients with elevated inflammatory markers and hypoxemia secondary to COVID-19. Methods: We conducted a 24-week randomized, double-blind, placebo-controlled trial, BREATHE (Better Respiratory Education and Treatment Help Empower), at 21 locations in the United States. Patients were randomized 1:1 to receive two doses of intravenous gimsilumab or placebo 1 week apart. The primary endpoint was all-cause mortality rate at Day 43. Key secondary outcomes were ventilator-free survival rate, ventilator-free days, and time to hospital discharge. Enrollment was halted early for futility based on an interim analysis. Measurements and Main Results: Of the planned 270 patients, 225 were randomized and dosed; 44.9% of patients were Hispanic or Latino. The gimsilumab and placebo groups experienced an all-cause mortality rate at Day 43 of 28.3% and 23.2%, respectively (adjusted difference = 5% vs. placebo; 95% confidence interval [-6 to 17]; P = 0.377). Overall mortality rates at 24 weeks were similar across the treatment arms. The key secondary endpoints demonstrated no significant differences between groups. Despite the high background use of corticosteroids and anticoagulants, adverse events were generally balanced between treatment groups. Conclusions: Gimsilumab did not improve mortality or other key clinical outcomes in patients with COVID-19 pneumonia and evidence of systemic inflammation. The utility of anti-GM-CSF therapy for COVID-19 remains unclear. Clinical trial registered with www.clinicaltrials.gov (NCT04351243).

Posterior left pericardiotomy for the prevention of atrial fibrillation after cardiac surgery: an adaptive, single-centre, single-blind, randomised, controlled trial.

BACKGROUND: Atrial fibrillation is the most common complication after cardiac surgery and is associated with extended in-hospital stay and increased adverse outcomes, including death and stroke. Pericardial effusion is common after cardiac surgery and can trigger atrial fibrillation. We tested the hypothesis that posterior left pericardiotomy, a surgical manoeuvre that drains the pericardial space into the left pleural cavity, might reduce the incidence of atrial fibrillation after cardiac surgery. METHODS: In this adaptive, randomised, controlled trial, we recruited adult patients (aged ≥18 years) undergoing elective interventions on the coronary arteries, aortic valve, or ascending aorta, or a combination of these, performed by members of the Department of Cardiothoracic Surgery from Weill Cornell Medicine at the New York Presbyterian Hospital in New York, NY, USA. Patients were eligible if they had no history of atrial fibrillation or other arrhythmias or contraindications to the experimental intervention. Eligible patients were randomly assigned (1:1), stratified by CHA2DS2-VASc score and using a mixed-block randomisation approach (block sizes of 4, 6, and 8), to posterior left pericardiotomy or no intervention. Patients and assessors were blinded to treatment assignment. Patients were followed up until 30 days after hospital discharge. The primary outcome was the incidence of atrial fibrillation during postoperative in-hospital stay, which was assessed in the intention-to-treat (ITT) population. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT02875405, and is now complete. FINDINGS: Between Sept 18, 2017, and Aug 2, 2021, 3601 patients were screened and 420 were included and randomly assigned to the posterior left pericardiotomy group (n=212) or the no intervention group (n=208; ITT population). The median age was 61·0 years (IQR 53·0-70·0), 102 (24%) patients were female, and 318 (76%) were male, with a median CHA2DS2-VASc score of 2·0 (IQR 1·0-3·0). The two groups were balanced with respect to clinical and surgical characteristics. No patients were lost to follow-up and data completeness was 100%. Three patients in the posterior left pericardiotomy group did not receive the intervention. In the ITT population, the incidence of postoperative atrial fibrillation was significantly lower in the posterior left pericardiotomy group than in the no intervention group (37 [17%] of 212 vs 66 [32%] of 208 [p=0·0007]; odds ratio adjusted for the stratification variable 0·44 [95% CI 0·27-0·70; p=0·0005]). Two (1%) of 209 patients in the posterior left pericardiotomy group and one (<1%) of 211 in the no intervention group died within 30 days after hospital discharge. The incidence of postoperative pericardial effusion was lower in the posterior left pericardiotomy group than in the no intervention group (26 [12%] of 209 vs 45 [21%] of 211; relative risk 0·58 [95% CI 0·37-0·91]). Postoperative major adverse events occurred in six (3%) patients in the posterior left pericardiotomy group and in four (2%) in the no intervention group. No posterior left pericardiotomy related complications were seen. INTERPRETATION: Posterior left pericardiotomy is highly effective in reducing the incidence of atrial fibrillation after surgery on the coronary arteries, aortic valve, or ascending aorta, or a combination of these without additional risk of postoperative complications. FUNDING: None.

Surgical debranching versus branched endografting in zone 2 thoracic endovascular aortic repair.

BACKGROUND: Left subclavian artery (LSA) revascularization has been recommended for patients undergoing elective thoracic endovascular aortic repair (TEVAR) with a proximal zone 2 landing requiring coverage of the LSA. The clinical standard of care remains surgical LSA revascularization. However, recently, the feasibility of using branched endografts has been demonstrated. We compared the perioperative and mid-term outcomes of these approaches. METHODS: We performed a retrospective review of consecutive patients who underwent TEVAR with a proximal zone 2 landing at a single center from 2014 to 2020. The patients were divided into cohorts for comparison: those who underwent surgical revascularization (SR-TEVAR group) and those who underwent thoracic branched endografting with an investigational device (TBE group). Those patients who did not undergo LSA revascularization were excluded. Perioperative outcomes, including procedural success, death, stroke, limb ischemia, and length of stay, were compared. Kaplan-Meier survival curves were compared using the log-rank test. The cumulative incidence of device-related endoleak (types I and III) and device-related reintervention, accounting for death as a competing hazard, were compared using the Fine-Gray test. RESULTS: A total of 55 patients were included: 31 (56%) in the SR-TEVAR group and 24 (44%) in the TBE group. The preoperative demographics and comorbidities were similar between the two groups. Procedural success was 100% in both cohorts, with no periprocedural strokes or left upper extremity ischemic events. One operative or 30-day death (TBE, 4.2%; vs SR-TEVAR, 3.2%; P = .99) occurred in each cohort. The total operative time (TBE, 203 ± 79 minutes; vs SR-TEVAR, 250 ± 79 minutes; P = .03) and total length of stay (TBE, 5.2 ± 3.6 days; vs SR-TEVAR, 9.9 ± 7.2 minutes; P = .004) were both significantly shorter in the TBE group. No difference was found in mid-term survival (log-rank test, P = .50) nor the cumulative incidence of device-related endoleak (Fine-Gray test, P = .51) or reintervention (Fine-Gray test, P = .72). No occlusions of the TBE graft or surgical bypass or transpositions had occurred after a mean follow-up of 28 ± 16 and 34 ± 24 months, respectively. CONCLUSIONS: TBE can be performed with procedural success rate and safety profile comparable to those of TEVAR with surgical revascularization, with a decreased total length of stay, for patients requiring proximal zone 2 coverage. The mid-term outcomes for each approach were also similar. Prospective, randomized comparisons of these techniques are warranted.

Machine learning analysis of multispectral imaging and clinical risk factors to predict amputation wound healing.

OBJECTIVE: Prediction of amputation wound healing is challenging due to the multifactorial nature of critical limb ischemia and lack of objective assessment tools. Up to one-third of amputations require revision to a more proximal level within 1 year. We tested a novel wound imaging system to predict amputation wound healing at initial evaluation. METHODS: Patients planned to undergo amputation due to critical limb ischemia were prospectively enrolled. Clinicians evaluated the patients in traditional fashion, and all clinical decisions for amputation level were determined by the clinician's judgement. Multispectral images of the lower extremity were obtained preoperatively using a novel wound imaging system. Clinicians were blinded to the machine analysis. A standardized wound healing assessment was performed on postoperative day 30 by physical exam to determine whether the amputation site achieved complete healing. If operative revision or higher level of amputation was required, this was undertaken based solely upon the provider's clinical judgement. A machine learning algorithm combining the multispectral imaging data with patient clinical risk factors was trained and tested using cross-validation to measure the wound imaging system's accuracy of predicting amputation wound healing. RESULTS: A total of 22 patients undergoing 25 amputations (10 toe, five transmetatarsal, eight below-knee, and two above-knee amputations) were enrolled. Eleven amputations (44%) were non-healing after 30 days. The machine learning algorithm had 91% sensitivity and 86% specificity for prediction of non-healing amputation sites (area under curve, 0.89). CONCLUSIONS: This pilot study suggests that a machine learning algorithm combining multispectral wound imaging with patient clinical risk factors may improve prediction of amputation wound healing and therefore decrease the need for reoperation and incidence of delayed healing. We propose that this, in turn, may offer significant cost savings to the patient and health system in addition to decreasing length of stay for patients.

Blood Product Utilization in Patients With COVID-19 on ECMO.

INTRODUCTION: Although extracorporeal membrane oxygenation (ECMO) has been associated with improved outcomes in COVID patients with respiratory failure, data regarding the need for blood product utilization in this population is inadequate. METHODS: We conducted a retrospective review of all COVID patients requiring ECMO support at our facility. Patient demographics, co-morbidities, measures of acuity, and blood product utilization were identified. Patients were stratified by the presence of a major bleed and the need for dialysis. The primary outcome was blood product utilization. Linear regression models were used to assess predictors of the need for blood products. RESULTS: From 2020 to 2021, 41 patients with COVID-19 were included in our study. Overall 1601 d of support, COVID ECMO patients received 755 units of packed red blood cells (PRBC), 51 units of fresh frozen plasma (FFP), 326 platelets, and 1702 cryoprecipitate, amounting to 18.4 units PRBC per patient or 3.30 units per week of ECMO support. Both major bleeding and the need for dialysis were associated with higher rates of transfusion of PRBC, FFP, and platelets. The average non-bleeding COVID ECMO patient who did not need dialysis required 2.17 units of PRBC, 0.12 units of FFP, 0.76 platelets, and 8.36 of cryoprecipitate per week of ECMO support. On multivariable linear regression analysis, each day on ECMO was associated with 0.30 [0.19-0.42, P < 0.01] units of PRBC. CONCLUSIONS: In conclusion, COVID ECMO is associated with a significant need for blood and blood products. Major bleeding and dialysis are important drivers of blood product requirements.

Development of a non-transplant left ventricular assist device program.

INTRODUCTION: Although the established long-term benefit of left ventricular assist device (LVAD) therapy has led to its proliferation as destination therapy (DT), few studies have evaluated LVAD outcomes at nontransplant centers. We undertook this study to better evaluate our experience in building a nontransplant, DT LVAD program. METHODS: We conducted a retrospective review of all LVADs implanted from 2010 to 2021. Patient, operative, and outcome data were extracted from the electronic medical record. Secular trends were evaluated by organizing the data into eras of implant. Survival was assessed using the Kaplan-Meier method. Multivariable Cox proportional hazards regression models further evaluated outcomes. RESULTS: From 2010 to 2021, 100 primary LVAD implants were performed. Annual volume grew from 1 to 30 implants per year. The average age of our cohort was 65.7 years, most patients (80%) were male, 51% had an ischemic etiology, and 65 (65%) were INTERMACS profile 1 or 2. Our 1- and 2-year survival were 82% and 79%, respectively. Multivariable analysis of 1-year mortality demonstrated that decreasing renal function and increased cardiopulmonary bypass (CPB) time were associated with increased mortality while preoperative hemoglobin was protective. When stratified by era of implant, our most recent patients were more likely to be INTERMACS profile 1 or 2; had shorter CPB and aortic cross clamp times; required fewer reoperations for bleeding; and suffered less right ventricular failure requiring mechanical support. CONCLUSIONS: A single, nontransplant LVAD center can experience significant growth in volume in a high-acuity cohort while maintaining acceptable outcomes and quality of care.

Outcomes of aortic root enlargement during isolated aortic valve replacement.

OBJECTIVES: Aortic root enlargement (ARE) lowers the risk of patient prosthesis mismatch after surgical aortic valve replacement (SAVR) in patients with small annular size. Whether ARE is associated with increased operative mortality is controversial. This study compares the early and intermediate outcomes in patients undergoing SAVR with and without ARE. METHODS: All patients undergoing isolated SAVR with and without ARE from 2015 to 2020 were analyzed. Propensity-matching was used to adjust for possible confounding variables. Kaplan-Meier analysis and log-rank test were used to estimate and compare overall outcomes and survival in the study cohorts. RESULTS: Among 868 isolated SAVRs, ARE was performed in 54 (6.2%) patients. Before matching, mean age was similar but female sex (67.4% vs. 29.6%; SD: -0.82) and previous AVR (18.9% vs. 3.9%; SD: -0.48) were more common in patients undergoing SAVR + ARE versus SAVR alone. A bovine pericardial patch was used for 81.5% (44 of 54) of ARE, with a Dacron patch in the rest. After propensity matching, the average cardiopulmonary bypass (138.2 ± 34.9 vs. 102.9 ± 33.0 min; p < 0.01) and cross-clamp times (113.8 ± 26.7 vs. 83.0 ± 28.4 min; p < 0.01) were longer in the SAVR + ARE group. There were no significant differences in postoperative stroke, new-onset dialysis, pacemaker placement, reoperation for bleeding, length of hospital stay, or 30-day readmission. Thirty-day mortality (0% vs. 0.6%, p = 1.0) and 5-year survival (96.3% vs. 95.7%, p = 0.86) were also similar. CONCLUSIONS: ARE during surgical AVR can be safely performed without an increase in complications with excellent early and intermediate-term survival.

Extracorporeal membrane oxygenation for respiratory failure in phases of COVID-19 variants.

BACKGROUND: Adaptive mutations of the severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) virus have emerged throughout the coronavirus disease 2019 (COVID-19) pandemic. The characterization of outcomes in patients requiring extracorporeal membrane oxygenation (ECMO) for severe respiratory distress from COVID-19 during the peak prevalence of different variants is not well known. METHODS: There were 131 patients with laboratory-confirmed SARS-CoV-2 infection supported by ECMO at two referral centers within a large healthcare system. Three predominant variant phase time windows (Pre-Alpha, Alpha, and Delta) were determined by a change-point analyzer based on random population sampling and viral genome sequencing. Patient demographics and outcomes were compared. RESULTS: The average age of patients was 46.9 ± 10.5 years and 70.2% (92/131) were male. Patients cannulated for ECMO during the Delta variant wave were younger compared to earlier Pre-Alpha (39.3 ± 7.8 vs. 48.0 ± 11.1 years) and Alpha phases (39.3 ± 7.8 vs. 47.2 ± 7.7 years) (p < .01). The predominantly affected race in the Pre-Alpha phase was Hispanic (52.2%; 47/90), while in Alpha (61.5%; 16/26) and Delta (40%; 6/15) variant waves, most patients were White (p < .01). Most patients received a tracheostomy (82.4%; 108/131) with a trend toward early intervention in later phases compared to Pre-Alpha (p < .01). There was no significant difference between the duration of ECMO, mechanical support, intensive care unit (ICU) length of stay (LOS), or hospital LOS over the three variant phases. The in-hospital mortality was overall 41.5% (54/131) and was also similar. Six-month survival of patients who survived to discharge was 92.2% (71/77). CONCLUSIONS: There was no significant difference in survival or time on ECMO support in patients during the peak prevalence of the three variants.

Trends in HeartMate 3: What we know so far.

BACKGROUND: The HeartMate 3 left ventricular assist device (LVAD) is a novel, intrapericardial, centrifugal-flow pump with a fully magnetically-levitated rotor designed to provide hemodynamic support in patients with end-stage heart failure. Unique aspects of this LVAD have allowed for improved hemocompatibility and the development of minimally-invasive implantation techniques. METHODS: The PubMed, EMBASE, and Google Scholar databases were searched for publications relating to the HeartMate 3 device, with a focus on hemocompatibility related outcomes, anticoagulation management, and surgical techniques. RESULTS: Nine articles analyzing hemocompatibility related outcomes from two clinical trials, two clinical studies, and one registry series were identified. CONCLUSION: HeartMate 3 has reduced the rate of disabling stroke and pump thrombosis. However, despite increased hemocompatibility due to specialized design features, the residual risk of both surgical, and gastrointestinal bleeding remains a major adverse outcome. Different anticoagulation management and surgical techniques have been evaluated to address the remaining complications.

Utilization of high donor sequence number grafts in cardiac transplantation.

Donor sequence number (DSN) represents the number of candidates to whom a graft was offered and declined prior to acceptance for transplantation. We sought to investigate the outcomes of patients receiving high DSN grafts. Consecutive isolated adult cardiac transplantations performed at a single-center were reviewed. Recipients were grouped into standard (≤75th percentile) DSN and high (>75th percentile) DSN. A previously validated donor risk index was used to quantify the risk associated with donor grafts, and recipient outcomes were assessed. Overall, 254 patients were included: 194 standard DSN (range 1-79) and 60 high DSN (range 82-1723). High DSN grafts were harvested at greater distance (P < .001) with increased ischemia time (P < .001), resulting in a modest increase in donor risk index (1 point median difference, P = .014). High DSN recipients were less frequently listed as UNOS status 1A (P < .001). Despite a nonsignificant trend toward increased in-hospital/30-day mortality in high DSN recipients, there were no differences in primary graft dysfunction or 1-year survival (high DSN 89% vs standard DSN 88%, P = .82). After adjustment for risk factors, high DSN was not associated with increased 1-year mortality (hazard ratio 1.18, 95%-CI 0.54-2.58, P = .68).

Influence of Baseline Characteristics, Operative Conduct, and Postoperative Course on 30-Day Outcomes of Coronary Artery Bypass Grafting Among Patients With Left Ventricular Dysfunction: Results From the Surgical Treatment for Ischemic Heart Failure (STICH) Trial.

BACKGROUND: Patients with severe left ventricular dysfunction, ischemic heart failure, and coronary artery disease suitable for coronary artery bypass grafting (CABG) are at higher risk for surgical morbidity and mortality. Paradoxically, those patients with the most severe coronary artery disease and ventricular dysfunction who derive the greatest clinical benefit from CABG are also at the greatest operative risk, which makes decision making regarding whether to proceed to surgery difficult in such patients. To better inform such decision making, we analyzed the Surgical Treatment for Ischemic Heart Failure (STICH) CABG population for detailed information on perioperative risk and outcomes. METHODS AND RESULTS: In both STICH trials (hypotheses), 2136 patients with a left ventricular ejection fraction of ≤35% and coronary artery disease were allocated to medical therapy, CABG plus medical therapy, or CABG with surgical ventricular reconstruction. Relationships of baseline characteristics and operative conduct with morbidity and mortality at 30 days were evaluated. There were a total of 1460 patients randomized to and receiving surgery, and 346 (≈25%) of these high-risk patients developed a severe complication within 30 days. Worsening renal insufficiency, cardiac arrest with cardiopulmonary resuscitation, and ventricular arrhythmias were the most frequent complications and those most commonly associated with death. Mortality at 30 days was 5.1% and was generally preceded by a serious complication (65 of 74 deaths). Left ventricular size, renal dysfunction, advanced age, and atrial fibrillation/flutter were significant preoperative predictors of mortality within 30 days. Cardiopulmonary bypass time was the only independent surgical variable predictive of 30-day mortality. CONCLUSIONS: CABG can be performed with relatively low 30-day mortality in patients with left ventricular dysfunction. Serious postoperative complications occurred in nearly 1 in 4 patients and were associated with mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Multi-disciplinary surgical approach to the management of patients with renal cell carcinoma with venous tumor thrombus: 15 year experience and lessons learned.

BACKGROUND: The management of patients with renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is challenging. We report our 15 year experience in the management of patients with RCC with VTT utilizing a multidisciplinary team approach, highlighting improved total and specifically Clavien III-V complication rates. METHODS: We reviewed the records of 146 consecutive patients who underwent radical nephrectomy with venous thrombectomy between 1998 and 2012. Data on patient history, staging, surgical techniques, morbidity, and survival were analyzed. Additionally, complication rates between two surgical eras, 1998-2006 and 2006-2012, were assessed. RESULTS: The study included 146 patients, 97 males (66 %), and a median age of 61 years (range, 24-83). Overall complications rate was 53 %, high grade complications (Clavien III -V) occurred in 10 % of patients. Most importantly, there was a lower incidence of overall and high grade complications (45 % and 8 %, respectively) in the last 6 years compared to the earlier surgeries included in the study (67 % and 13 % respectively) [p = .008 and .03, respectively). 30 day postoperative mortality was 2.7 %. 5 year overall survival (5Y- OS) and 5 year cancer specific survival (5Y- CSS) were 51 % and 40 %, respectively. Metastasis was the only independent predictor factor for CSS (HR 3.8, CI 1.9-7.6 and p < .001) and OS (HR 2.6, CI 1.5-4.7 and p = .001) in all patients. CONCLUSIONS: Our data suggest that patients with RCC and VTT can be treated safely utilizing a multidisciplinary team approach leading to a decrease in complication rates.

Reprogramming of human fibroblasts toward a cardiac fate.

Reprogramming of mouse fibroblasts toward a myocardial cell fate by forced expression of cardiac transcription factors or microRNAs has recently been demonstrated. The potential clinical applicability of these findings is based on the minimal regenerative potential of the adult human heart and the limited availability of human heart tissue. An initial but mandatory step toward clinical application of this approach is to establish conditions for conversion of adult human fibroblasts to a cardiac phenotype. Toward this goal, we sought to determine the optimal combination of factors necessary and sufficient for direct myocardial reprogramming of human fibroblasts. Here we show that four human cardiac transcription factors, including GATA binding protein 4, Hand2, T-box5, and myocardin, and two microRNAs, miR-1 and miR-133, activated cardiac marker expression in neonatal and adult human fibroblasts. After maintenance in culture for 4-11 wk, human fibroblasts reprogrammed with these proteins and microRNAs displayed sarcomere-like structures and calcium transients, and a small subset of such cells exhibited spontaneous contractility. These phenotypic changes were accompanied by expression of a broad range of cardiac genes and suppression of nonmyocyte genes. These findings indicate that human fibroblasts can be reprogrammed to cardiac-like myocytes by forced expression of cardiac transcription factors with muscle-specific microRNAs and represent a step toward possible therapeutic application of this reprogramming approach.