Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass.

OBJECTIVES: Quantify the relationship between perioperative anaerobic lactate production, microcirculatory blood flow, and mitochondrial respiration in patients after cardiovascular surgery with cardiopulmonary bypass. DESIGN: Serial measurements of lactate-pyruvate ratio (LPR), microcirculatory blood flow, plasma tricarboxylic acid cycle cycle intermediates, and mitochondrial respiration were compared between patients with a normal peak lactate (≤ 2 mmol/L) and a high peak lactate (≥ 4 mmol/L) in the first 6 hours after surgery. Regression analysis was performed to quantify the relationship between clinically relevant hemodynamic variables, lactate, LPR, and microcirculatory blood flow. SETTING: This was a single-center, prospective observational study conducted in an academic cardiovascular ICU. PATIENTS: One hundred thirty-two patients undergoing elective cardiovascular surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with a high postoperative lactate were found to have a higher LPR compared with patients with a normal postoperative lactate (14.4 ± 2.5 vs. 11.7 ± 3.4; p = 0.005). Linear regression analysis found a significant, negative relationship between LPR and microcirculatory flow index (r = -0.225; ß = -0.037; p = 0.001 and proportion of perfused vessels: r = -0.17; ß = -0.468; p = 0.009). There was not a significant relationship between absolute plasma lactate and microcirculation variables. Last, mitochondrial complex I and complex II oxidative phosphorylation were reduced in patients with high postoperative lactate levels compared with patients with normal lactate (22.6 ± 6.2 vs. 14.5 ± 7.4 pmol O2/s/106 cells; p = 0.002). CONCLUSIONS: Increased anaerobic lactate production, estimated by LPR, has a negative relationship with microcirculatory blood flow after cardiovascular surgery. This relationship does not persist when measuring lactate alone. In addition, decreased mitochondrial respiration is associated with increased lactate after cardiovascular surgery. These findings suggest that high lactate levels after cardiovascular surgery, even in the setting of normal hemodynamics, are not simply a type B phenomenon as previously suggested.

Transaortic TAVR and Mitral Repair Under Deep Hypothermic Circulatory Arrest in a Porcelain Aorta Patient.

Vascular and valvular calcifications, commonly seen in renal patients, increase operative mortality and can preclude conventional valvular management. We show a novel approach to treat aortic stenosis and degenerative mitral regurgitation under hypothermic circulatory arrest in a hemodialysis patient with aortic, mitral disease and porcelain aorta with surgical and transcatheter contraindications.

Circulating T cell specific extracellular vesicle profiles in cardiac allograft acute cellular rejection.

There is a critical need for biomarkers of acute cellular rejection (ACR) in organ transplantation. We hypothesized that ACR leads to changes in donor-reactive T cell small extracellular vesicle (sEV) profiles in transplant recipient circulation that match the kinetics of alloreactive T cell activation. In rodent heart transplantation, circulating T cell sEV quantities (P < .0001) and their protein and mRNA cargoes showed time-specific expression of alloreactive and regulatory markers heralding early ACR in allogeneic transplant recipients but not in syngeneic transplant recipients. Next generation sequencing of their microRNA cargoes identified novel candidate biomarkers of ACR, which were validated by stem loop quantitative reverse transcription polymerase chain reaction (n = 10). Circulating T cell sEVs enriched from allogeneic transplant recipients mediated targeted cytotoxicity of donor cardiomyocytes by apoptosis assay (P < .0001). Translation of the concept and EV methodologies to clinical heart transplantation demonstrated similar upregulation of circulating T cell sEV profiles at time points of grade 2 ACR (n = 3 patients). Furthermore, T cell receptor sequencing of T cell sEV mRNA cargo demonstrated expression of T cell clones with intact complementarity determining region 3 signals. These data support the diagnostic potential of T cell sEVs as noninvasive biomarker of ACR and suggest their potential functional roles.

Infarct-related structural disconnection and delirium in surgical aortic valve replacement patients.

OBJECTIVE: Although acute brain infarcts are common after surgical aortic valve replacement (SAVR), they are often unassociated with clinical stroke symptoms. The relationship between clinically "silent" infarcts and in-hospital delirium remains uncertain; obscured, in part, by how infarcts have been traditionally summarized as global metrics, independent of location or structural consequence. We sought to determine if infarct location and related structural connectivity changes were associated with postoperative delirium after SAVR. METHODS: A secondary analysis of a randomized multicenter SAVR trial of embolic protection devices (NCT02389894) was conducted, excluding participants with clinical stroke or incomplete neuroimaging (N = 298; 39% female, 7% non-White, 74 ± 7 years). Delirium during in-hospital recovery was serially screened using the Confusion Assessment Method. Parcellation and tractography atlas-based neuroimaging methods were used to determine infarct locations and cortical connectivity effects. Mixed-effect, zero-inflated gaussian modeling analyses, accounting for brain region-specific infarct characteristics, were conducted to examine for differences within and between groups by delirium status and perioperative neuroprotection device strategy. RESULTS: 23.5% participants experienced postoperative delirium. Delirium was associated with significantly increased lesion volumes in the right cerebellum and temporal lobe white matter, while diffusion weighted imaging infarct-related structural disconnection (DWI-ISD) was observed in frontal and temporal lobe regions (p-FDR < 0.05). Fewer brain regions demonstrated DWI-ISD loss in the suction-based neuroprotection device group, relative to filtration-based device or standard aortic cannula. INTERPRETATION: Structural disconnection from acute infarcts was greater in patients who experienced postoperative delirium, suggesting that the impact from covert perioperative infarcts may not be as clinically "silent" as commonly assumed.

Low postoperative perfused vessel density is associated with increased soluble endothelial cell adhesion molecules during circulatory shock after cardiac surgery.

INTRODUCTION: Microcirculatory dysfunction after cardiovascular surgery is associated with significant morbidity and worse clinical outcomes. Abnormal capillary blood flow can occur from multiple causes, including cytokine-mediated vascular endothelial injury, microthrombosis, and an inadequate balance between vasoconstriction and vasodilation. In response to proinflammatory cytokines, endothelial cells produce cellular adhesion molecules (CAMs) which regulate leukocyte adhesion, vascular permeability, and thus can mediate tissue injury. The relationship between changes in microcirculatory flow during circulatory shock and circulating adhesion molecules is unclear. The objective of this study was to compare changes in plasma soluble endothelial cell adhesion molecules (VCAM-1, ICAM-1, and E-Selectin) in patients with functional derangements in microcirculatory blood flow after cardiovascular surgery. METHODS: Adult patients undergoing elective cardiac surgery requiring cardiopulmonary bypass who exhibited postoperative shock were enrolled in the study. Sublingual microcirculation imaging was performed prior to surgery and within 2 h of ICU admission. Blood samples were taken at the time of microcirculation imaging for biomarker analysis. Plasma soluble VCAM-1, ICAM-1, and E-selectin in addition to plasma cytokines (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunoassay. RESULTS: Of 83 patients with postoperative shock who were evaluated, 40 patients with clinical shock had a postoperative perfused vessel density (PVD) >1 SD above (High PVD group = 28.5 ± 2.3 mm/mm2, n = 20) or below (Low PVD = 15.5 ± 2.0 mm/mm2, n = 20) the mean postoperative PVD and were included in the final analysis. Patient groups were well matched for comorbidities, surgical, and postoperative details. Overall, there was an increase in postoperative plasma VCAM-1 and E-Selectin compared to preoperative levels, but there was no difference between circulating ICAM-1. When grouped by postoperative microcirculation, patients with poor microcirculation were found to have increased circulating VCAM-1 (2413 ± 1144 vs. 844 ± 786 ng/mL; p < 0.0001) and E-Selectin (242 ± 119 vs. 87 ± 86 ng/mL; p < 0.0001) compared to patients with increased microcirculatory blood flow. Microcirculatory flow was not associated with a difference in plasma soluble ICAM-1 (394 ± 190 vs. 441 ± 256; p = 0.52). CONCLUSIONS: Poor postoperative microcirculatory blood flow in patients with circulatory shock after cardiac surgery is associated with increased plasma soluble VCAM-1 and E-Selectin, indicating increased endothelial injury and activation compared to patients with a high postoperative microcirculatory blood flow. Circulating endothelial cell adhesion molecules may be a useful plasma biomarker to identify abnormal microcirculatory blood flow in patients with shock.

Effect of Anesthesia Induction on Cardiac Hemodynamics in Patients Undergoing Durable Left Ventricular Assist Device Implantation: The EACH-LVAD Study.

Right ventricular (RV) dysfunction is common after left ventricular assist device (LVAD) implantation leading to clinical right heart failure (RHF) associated with worsened survival and quality of life. It is likely that intraoperative events such as anesthesia induction play a role in the development or unmasking of RV dysfunction in addition to known effects from hemodynamic changes that occur after LVAD implantation. The EACH-LVAD Study is a prospective, single-center, single-arm, observational cohort study of adult patients with advanced heart failure undergoing durable LVAD implantation with standard anesthesia induction. Intraoperative RV hemodynamics via central venous pressure, mean pulmonary artery pressure, pulmonary artery pulsatility index, and vasoactive-inotropic score (a simple weighted summation of standardized drug doses) and echocardiographic parameters (RV fractional area change, RV area in diastole, RV basal diameter, septum position, RV function, tricuspid regurgitation) were measured and compared at prespecified timepoints, including postinduction. Postoperative clinical RHF was determined based on published definitions. Forty-two patients receiving a first-time LVAD were included between September 2017 and March 2019. Propofol-based induction was used in 31 patients and etomidate-based induction in eight patients. A significant increase in central venous pressure (CVP; p < 0.001), mean pulmonary artery pressure (mPAP; p < 0.001), and vasoactive inotropic score (VIS; p < 0.001) with associated decrease in pulmonary artery pulsatility index (PAPi; p < 0.001) was observed. Right ventricular function worsened throughout. Right heart failure occurred in 70% of patients. Propofol-based induction was not associated with a higher risk of RHF (relative risk [RR], 1.01 [95% confidence interval {CI}, 0.64-1.61]). The EACH-LVAD study demonstrates an effect of anesthesia induction on worsened RV hemodynamics and echocardiographic changes which may have an effect on the development of RHF.

Durable Left Ventricular Assist Device Outflow Graft Obstructions: Clinical Characteristics and Outcomes.

PURPOSE: We report on the clinical course and management of patients supported with durable implantable LVADs who developed outflow graft obstructions at a large academic center. METHODS: We performed a retrospective review of patients receiving LVAD support from 2012 through 2020. Patients who developed an outflow graft obstruction diagnosed by computed tomography angiography (CTA) or angiogram were identified, and patient characteristics and outcomes were reported. RESULTS: Of the 324 patients supported by LVAD at our institution, 11 patients (3.4%) were diagnosed with outflow graft obstructions. The most common presentation was low flow alarms, which was present in 10/11 patients, and the remaining patient presented with lightheadedness. Patients had minimal LDH elevation with 8/11 presenting with less than 2-fold the upper limit of normal. Transthoracic echocardiograms were not diagnostic, but CTA enabled non-invasive diagnoses in 8/11 of the patients. Three patients with extrinsic compression of the outflow graft successfully underwent endovascular stent placement, and three patients with outflow cannula kinks received supportive care. Of the five patients diagnosed with intraluminal thromboses, one received a heart transplant, one underwent an outflow graft revision, and three received supportive care due to comorbidities. CONCLUSION: Outflow graft obstructions remain a rare, but serious complication. The true prevalence of this entity is likely underestimated due to the non-specific clinical presentation. CTA is a pivotal non-invasive diagnostic step. Patients with external compression were successfully treated with endovascular stenting.

Early Cardiopulmonary Fitness after Heart Transplantation as a Determinant of Post-Transplant Survival.

BACKGROUND: Decreased peak oxygen consumption during exercise (peak Vo2) is a well-established prognostic marker for mortality in ambulatory heart failure. After heart transplantation, the utility of peak Vo2 as a marker of post-transplant survival is not well established. METHODS AND RESULTS: We performed a retrospective analysis of adult heart transplant recipients at the Hospital of the University of Pennsylvania who underwent cardiopulmonary exercise testing within a year of transplant between the years 2000 to 2011. Using time-to-event models, we analyzed the hazard of mortality over nearly two decades of follow-up as a function of post-transplant percent predicted peak Vo2 (%Vo2). A total of 235 patients met inclusion criteria. The median post-transplant %Vo2 was 49% (IQR 42 to 60). Each standard deviation (±14%) increase in %Vo2 was associated with a 32% decrease in mortality in adjusted models (HR 0.68, 95% CI 0.53 to 0.87, p = 0.002). A %Vo2 below 29%, 64% and 88% predicted less than 80% survival at 5, 10, and 15 years, respectively. CONCLUSIONS: Post-transplant peak Vo2 is a highly significant prognostic marker for long-term post-transplant survival. It remains to be seen whether decreased peak Vo2 post-transplant is modifiable as a target to improve post-transplant longevity.

Derivation and Validation of an Algorithm to Detect Stroke Using Arm Accelerometry Data.

Background Early diagnosis is essential for effective stroke therapy. Strokes in hospitalized patients are associated with worse outcomes compared with strokes in the community. We derived and validated an algorithm to identify strokes by monitoring upper limb movements in hospitalized patients. Methods and Results A prospective case-control study in hospitalized patients evaluated bilateral arm accelerometry from patients with acute stroke with lateralized weakness and controls without stroke. We derived a stroke classifier algorithm from 123 controls and 77 acute stroke cases and then validated the performance in a separate cohort of 167 controls and 33 acute strokes, measuring false alarm rates in nonstroke controls and time to detection in stroke cases. Faster detection time was associated with more false alarms. With a median false alarm rate among nonstroke controls of 3.6 (interquartile range [IQR], 2.1-5.0) alarms per patient per day, the median time to detection was 15.0 (IQR, 8.0-73.5) minutes. A median false alarm rate of 1.1 (IQR. 0-2.2) per patient per day was associated with a median time to stroke detection of 29.0 (IQR, 11.0-58.0) minutes. There were no differences in algorithm performance for subgroups dichotomized by age, sex, race, handedness, nondominant hemisphere involvement, intensive care unit versus ward, or daytime versus nighttime. Conclusions Arm movement data can be used to detect asymmetry indicative of stroke in hospitalized patients with a low false alarm rate. Additional studies are needed to demonstrate clinical usefulness.

Robotic and endoscopic mitral valve repair for degenerative disease.

Background: Minimally invasive mitral valve repair has been proven to be a safe alternative to open sternotomy and may be accomplished through classic endoscopic and robotic endoscopic approaches. Outcomes across different minimally invasive techniques have been insufficiently described. We compare early and late clinical outcomes across matched patients undergoing robotic endoscopic and classic endoscopic repair. Methods: From 2011 to 2020, 786 patients underwent minimally invasive mitral surgery, from which we were able to generate 124 matched patients (62 patients in each cohort). Clinical results were then compared between the two matched populations. Survival analysis was used to compare freedom from mortality to 10 years among matched classic endoscopic and robotic endoscopic mitral valve repair cohorts and to calculate freedom from moderate or severe mitral insufficiency at latest follow-up. Histograms of cardiopulmonary bypass (CPB) and aortic cross-clamp times were constructed, and mean bypass and cross-clamp times were compared between classic endoscopic and robotic endoscopic cohorts. Results: There was no difference in early or late mortality at 10 years in either cohort. Freedom from moderate or severe mitral regurgitation or mitral valve replacement at last echocardiogram was 86.4% vs. 73.5% at 10 years, P=0.97. Patients undergoing robotic endoscopic mitral repair had a significantly longer CPB run when compared to the classic endoscopic cohort, with 148 min of CPB in the robotic endoscopic cohort compared to 133 min in the classic endoscopic group, P=0.03. Overall post-operative length of stay was not statistically significant between the robotic endoscopic and classic endoscopic groups, 6.3±0.5 and 6.0±0.3 days, respectively. No patients in either cohort developed renal failure or wound infection. The classic endoscopic group had a slightly higher risk of prolonged ventilation when compared to the robotic endoscopic group, with three classic endoscopic patients remaining intubated >8 hours post-operatively, compared to a single patient in the robotic endoscopic group. There were no unplanned reoperations in either group. Rates of postoperative stroke were comparable between groups (three in the classic endoscopic cohort, and two in the robotic endoscopic cohort). Conclusions: Index mitral valve surgery via a classic endoscopic approach yields similar clinical outcomes when compared to robotic endoscopic surgery. We demonstrate that both classic endoscopic and robotic endoscopic approaches allow repair of degenerative mitral valves with excellent short- and medium-term outcomes in a tertiary referral center.

Intimal hyperplasia, saphenous vein graft disease, and clinical outcomes: Insights from the CTSN VEST randomized trial.

BACKGROUND: Diffuse intimal hyperplasia and graft irregularity adversely affect the long-term patency of saphenous vein grafts (SVGs) and clinical outcomes of patients undergoing coronary artery bypass grafting (CABG). The VEST trial evaluated the efficacy of external graft support in limiting the development of intimal hyperplasia (IH) at 1 year postsurgery. In the present secondary analysis, we explored the associations between graft disease and IH and clinical events. We also examined risk factors for early graft occlusion. METHODS: VEST is a within-patient randomized, multicenter trial that enrolled 224 patients with multivessel coronary disease undergoing CABG surgery, of whom 203 were evaluated by 1 year postsurgery. Intimal hyperplasia, lumen uniformity, graft stenosis, and graft perfusion were measured by intravascular ultrasound and angiography. Major cardiac and cerebrovascular events (MACCE; including death, myocardial infarction, stroke, and revascularization) were recorded over a median follow-up of 3 years. RESULTS: Worse lumen uniformity, greater stenosis, and worse graft perfusion were associated with higher IH values and an increased incidence of clinical events. Consistent with previous findings, we identified endoscopic vein harvesting, female sex, and transit time flow measurement of pulsatility index and flow as risk factors for SVG occlusion during the first year postsurgery. CONCLUSIONS: In this secondary analysis of the VEST trial, we observed an association between intimal hyperplasia area and clinical measures of SVG disease at 1 year postsurgery. More severe SVG disease and larger areas of IH were associated with a higher incidence of 3-year MACCE. Ongoing follow-up to 5 years will further elucidate the impact of SVG disease on long-term clinical outcomes of CABG.

Balancing quality and quaternary care imperative using a high-risk case review committee in adults.

OBJECTIVES: Quaternary care centres have an imperative to serve as hospitals of last resort and must also meet professional quality targets. We developed a high-risk committee (HRC) to evaluate cases meeting pre-defined predicted risk cut-offs as a part of an overall quality improvement drive. METHODS: We describe the structure, outcomes and effects of the Penn HRC. Using propensity-matching, we investigated whether the committee modifies or screens risk. We used multivariable analysis to examine the impact of unmeasured variables on clinical outcomes in this cohort. RESULTS: Institutional predicted and observed mortality had already been in decline prior to HRC institution in 2017, due to a multi-faceted quality improvement initiative. Between 2017 and 2020, the HRC discussed 205 patients with a median predicted risk of mortality of 10.6% (range 0.4-66%). Coronary artery bypass grafting was the most commonly presented operation. A total of 155 patients underwent operation (risk 10.3%), 12 had surgery deferred for optimization (risk 6%), 50 had surgery declined (risk 11.7%) and 12 patients had a deferred decision for further investigation. Overall 30-day survival was 86% for the entire cohort and 89% for operated patients. A matched analysis of similar patients prior to and following the HRC showed that the HRC did not directly modify outcomes. Most patients had better than expected survival (observed:expected mortality < 1). Predicted risk did not predict 30-day mortality among this high-risk cohort. CONCLUSIONS: HRCs serve as an important element in quality improvement by encouraging a thoughtful approach and channelling the collective experience of a group of senior surgeons. It may improve patient selection by identifying a cohort with extremely poor survival, while allowing safe operation with acceptable outcomes among a group with very high operative risk.

Topical nitroglycerin to detect reversible microcirculatory dysfunction in patients with circulatory shock after cardiovascular surgery: an observational study.

Persistent abnormalities in microcirculatory function are associated with poor clinical outcomes in patients with circulatory shock. We sought to identify patients with acutely reversible microcirculatory dysfunction using a low-dose topical nitroglycerin solution and handheld videomicroscopy during circulatory shock after cardiac surgery. Forty subjects were enrolled for the study, including 20 preoperative control and 20 post-operative patients with shock. To test whether microcirculatory dysfunction is acutely reversible during shock, the sublingual microcirculation was imaged with incident dark field microscopy before and after the application of 0.1 mL of a 1% nitroglycerin solution (1 mg/mL). Compared to the control group, patients with shock had a higher microcirculation heterogeneity index (MHI 0.33 vs. 0.12, p < 0.001) and a lower microvascular flow index (MFI 2.57 vs. 2.91, p < 0.001), total vessel density (TVD 22.47 vs. 25.90 mm/mm2, p = 0.005), proportion of perfused vessels (PPV 90.76 vs. 95.89%, p < 0.001) and perfused vessel density (PVD 20.44 vs. 24.81 mm/mm2, p < 0.001). After the nitroglycerin challenge, patients with shock had an increase in MFI (2.57 vs. 2.97, p < 0.001), TVD (22.47 vs. 27.51 mm/mm2, p < 0.009), PPV (90.76 vs. 95.91%, p < 0.001), PVD (20.44 vs. 26.41 mm/mm2, p < 0.001), venular RBC velocity (402.2 vs. 693.9 µm/s, p < 0.0004), and a decrease in MHI (0.33 vs. 0.04, p < 0.001. Thirteen of 20 patients showed a pharmacodynamic response, defined as an increase in PVD > 1.8 SD from shock baseline. Hemodynamics and vasoactive doses did not change during the 30-min study period. Our findings suggest a topical nitroglycerin challenge with handheld videomicroscopy can safely assess for localized recruitment of the microcirculatory blood flow in patients with circulatory shock and may be a useful test to identify nitroglycerin responsiveness.

The Anemia Stress Index-Anemia, Transfusions, and Mortality in Patients with Continuous Flow Ventricular Assist Devices.

We aimed to identify a simple metric accounting for peri-procedural hemoglobin changes, independent of blood product transfusion strategies, and assess its correlation with outcomes in patients undergoing left ventricular assist device (LVAD) implantation We included consecutive patients undergoing LVAD implantation at a single center between 10/1/2008 and 6/1/2014. The anemia stress index (ASI), defined as the sum of number of packed red blood cells transfused and the hemoglobin changes after LVAD implantation, was calculated for each patient at 24 h, discharge, and 3 months after LVAD implantation. Our cohort included 166 patients (80.1% males, mean age 56.3 ± 15.6 years) followed up for a median of 12.3 months. Increases in ASI per unit were associated with a higher hazard for all-cause mortality and early RV failure. The associations between the ASI and all-cause mortality persisted after multivariable adjustment, irrespective of when it was calculated (adjusted HR of 1.11, 95% CI 1.03-1.20 per unit increase in ASI). Similarly, ASI at 24 h after implant was associated with early RV failure despite multivariable adjustment (OR 1.09, 95% CI 1.05-1.14). We present a novel metric, the ASI, that is correlated with an increased risk for all-cause mortality and early RV failure in LVAD recipients.

Protocol for the MicroRESUS study: The impact of circulatory shock and resuscitation on microcirculatory function and mitochondrial respiration after cardiovascular surgery.

BACKGROUND: Despite current resuscitation strategies, circulatory shock and organ injury after cardiac surgery occur in 25-40% of patients. Goal-directed resuscitation after cardiac surgery has generated significant interest, but clinical practice to normalize hemodynamic variables including mean arterial pressure, cardiac filling pressures, and cardiac output may not reverse microcirculation abnormalities and do not address cellular dysoxia. Recent advances in technology have made it possible to measure critical components of oxygen delivery and oxygen utilization systems in live human tissues and blood cells. The MicroRESUS study will be the first study to measure microcirculatory and mitochondrial function in patients with circulatory shock and link these findings with clinical outcomes. METHODS AND ANALYSIS: This will be a prospective, observational study that includes patients undergoing elective cardiovascular surgery with cardiopulmonary bypass (CPB). Microcirculation will be quantified with sublingual incident dark field videomicroscopy. Mitochondrial respiration will be measured by performing a substrate-uncoupler-inhibitor titration protocol with high resolution respirometry on peripheral blood mononuclear cells at baseline and serial timepoints during resuscitation and at recovery as a possible liquid biomarker. Plasma samples will be preserved for future analysis to examine endothelial injury and other mechanisms of microcirculatory dysfunction. Thirty-day ventilator and vasopressor-free days (VVFDs) will be measured as a primary outcome, along with sequential organ failure assessment scores, and other clinical parameters to determine if changes in microcirculation and mitochondrial respiration are more strongly associated with clinical outcomes compared to traditional resuscitation targets. DISCUSSION: This will be the first prospective study to examine both microcirculatory and mitochondrial function in human patients with circulatory shock undergoing cardiac bypass and address a key mechanistic knowledge gap in the cardiovascular literature. The results of this study will direct future research efforts and therapeutic development for patients with shock.

Safety and Effectiveness of Intravenous Iron Therapy in Patients Supported by Durable Left Ventricular Assist Devices.

AIMS: While it is common practice to use intravenous (IV) iron in patients with left ventricular assist devices (LVADs) and iron deficiency, there is insufficient evidence regarding outcomes in this patient population. We evaluated the safety and effectiveness of IV iron therapy in patients supported by LVADs with iron deficiency. METHODS: We performed a retrospective analysis of iron deficient patients on continuous LVAD support at a large academic center between 2008 and 2019. Patients were divided into two cohorts based on IV iron sucrose treatment. The primary endpoint was hemoglobin at 12 weeks. Secondary endpoints were mean corpuscular volume (MCV) and New York Heart Association (NYHA) class at 12 weeks. Safety endpoints included hospitalization, infection, pump thrombosis, arrhythmia, and gastrointestinal bleed. Models were weighted by the inverse probability of receiving IV iron using a propensity score, and endpoints were adjusted for their corresponding baseline values. RESULTS: Among 213 patients, 70 patients received IV iron and 143 patients did not. Hemoglobin at 12 weeks was significantly greater among those treated (intergroup difference: 0.6 g/dL; 95% CI, 0.1 to 1.1; p = 0.01), while MCV was similar in both groups (intergroup difference: 0.7 µm3; 95% CI, -1.3 to 2.7; p = 0.50). NYHA class distribution at 12 weeks was significantly different (odds ratio for improvement: 2.84; 95% CI, 1.42 to 4.68; p = 0.003). The hazards of adverse events in each group were similar. CONCLUSIONS: In patients with LVADs and iron deficiency, treatment with IV iron sucrose was safe and associated with improvements in functional status and hemoglobin.

External Support for Saphenous Vein Grafts in Coronary Artery Bypass Surgery: A Randomized Clinical Trial.

Importance: Intimal hyperplasia and subsequent saphenous vein graft failure may have significant adverse clinical effects in patients undergoing coronary artery bypass surgery. External support of saphenous vein grafts has the potential to prevent vein graft dilation and hence slow the rate of intimal hyperplasia and increase long-term vein patency. Objective: To determine efficacy, as measured by intimal hyperplasia, and safety of an external saphenous vein graft support device in patients undergoing a coronary bypass graft procedure. Design, Setting, and Participants: This within-patient randomized, open-label, multicenter study was conducted at 17 Cardiothoracic Surgical Trials Network centers in North America. Between January 2018 and February 2019, 224 patients with multivessel coronary artery disease undergoing isolated bypass surgery were enrolled. For each patient, 1 of 2 vein grafts was randomized to receive external support or no support. Interventions: External vein graft support or no support. Main Outcomes and Measures: The primary efficacy end point was intimal hyperplasia area assessed by intravascular ultrasound at 12 months postrandomization for each study graft. Secondary confirmatory end points were lumen diameter uniformity assessed by angiography and graft failure (≥50% stenosis) by quantitative coronary angiography. Major cardiac and cerebrovascular events were collected through month 12. Results: Among 224 patients (mean [SD] age, 65.8 [8.3] years; 178 [79.5%] male), 203 (90.6%) were eligible for intravascular ultrasound, of which 85 (41.9%) had at least 1 study graft occluded or severely diseased at 12 months (55 supported, 56 unsupported). After imputation of data missing because of graft occlusion or severe disease, the estimated mean (SE) intimal hyperplasia area was 5.11 (0.16) mm2 in supported grafts and 5.79 (0.20) mm2 in unsupported grafts (P = .07). In a sensitivity analysis of 113 patients with both grafts imaged, the mean intimal hyperplasia area was 4.58 (0.18) mm2 and 5.12 (0.23) mm2 in supported and unsupported grafts, respectively (P = .04). By 12 months, 5 patients (2.2%) died and 16 patients (7.1%) experienced a major cardiac or cerebrovascular event. Conclusions and Relevance: The 12-month difference in intimal hyperplasia area between supported and unsupported grafts did not achieve statistical significance. Cumulative mortality and major cardiac or cerebrovascular events rates were similar to those in other randomized coronary artery bypass trials. Further investigation to assess the effect of external graft support devices on long-term graft patency and clinical outcomes is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03209609.

Delays in the Identification and Assessment of in-Hospital Stroke Patients.

OBJECTIVES: In-hospital stroke is associated with poor outcomes. Reasons for delays, use of interventions, and presence of large vessel occlusion are not well characterized. MATERIALS AND METHODS: A retrospective single center cohort of 97 patients with in-hospital stroke was analyzed to identify factors associated with delays from last known normal to symptom identification and to stroke team alerting. Stroke interventions and presence of large vessel occlusion were also assessed. RESULTS: Strokes were predominantly on surgery services (70%), ischemic (82%), and severe (median NIHSS 16; interquartile range [IQR] 6-24). There were long delays from last known normal to symptom identification (median 5.1 hours, IQR 1.0-19.7 hours), symptom identification to stroke team alerting (median 2.1 hours, IQR 0.5-9.9 hours), and total time from last known normal to alerting (median 11.4 [IQR 2.7-34.2] hours). In univariable analysis, being on a surgical service, in an ICU, intubated, and higher NIHSS were associated with delays. In multivariable analysis only intubation was independently associated with time from last known normal to symptom identification (coefficient 20 hours, IQR 0.2 - 39.8, p=0.047). Interventions were given to 17/80 (21%) ischemic stroke patients; 3 (4%) received IV tPA and 14 (18%) underwent thrombectomy. Vascular imaging occurred in 57/80 (71%) ischemic stroke patients and 21/57 (37%) had large vessel occlusion. CONCLUSIONS: Hospitalized patients with stroke experience long delays from symptom identification to stroke team alerting. Intubation was strongly associated with delay to symptom identification. Although stroke severity was high and large vessel occlusion common, many patients did not receive acute interventions.

Left Ventricular Assist Device as a Bridge to Recovery: Single Center Experience of Successful Device Explantation.

Continuous-flow left ventricular assist devices (CF-LVAD) have been shown to enhance reverse remodeling and myocardial recovery in certain patients allowing for device removal. We sought to analyze the characteristics and describe outcomes of patients who underwent CF-LVAD explantation at a large academic center. We retrospectively identified all patients who underwent CF-LVAD explants due to recovery from 2006 to 2019. Patient baseline characteristics and data on pre- and postexplant evaluation were collected and analyzed. Of 421 patients who underwent CF-LVAD implantation, 13 underwent explantation (3.1%). Twelve HeartMate II and one HeartWare LVAD were explanted. All patients had nonischemic cardiomyopathy. Median time from heart failure diagnosis to LVAD implant was 12 months (interquartile range [IQR], 2-44) and the median time supported on LVAD was 22 months (IQR, 11-28). Two patients died within 30 days of explant. Three additional patients died during the follow-up period and all were noted to be nonadherent to medical therapy. After a mean follow-up duration of 5 years, overall survival was 52%. Mean pre-explant ejection fraction was 49%, which decreased at most recent follow-up to 32%. Mean pre-explant left ventricular internal diameter in diastole (LVIDD) was 4.37 cm and increased to 5.52 cm at most recent follow-up. Continuous-flow left ventricular assist device explantation is feasible and safe in select patients.

Optimal Surgical Approach to Left Atrioesophageal Fistula After Catheter Radiofrequency Ablation.

Atrioesophageal fistula formation is a rare but formidable complication after catheter radiofrequency ablation for atrial fibrillation. We present 4 patients who underwent urgent primary intracardiac repair of the left atrium via sternotomy with central cardiopulmonary bypass and early aortic cross-clamp, followed by repair of the esophagus. We believe that this approach represents the safest strategy for addressing this morbid and often fatal complication.