Elevated cardiac hemoglobin expression is associated with a pro-oxidative and inflammatory environment in primary mitral regurgitation.

BACKGROUND: Primary mitral regurgitation (PMR) is associated with oxidative and inflammatory myocardial damage. We reported greater exosome hemoglobin (Hb) in pericardial fluid (PCF) versus plasma, suggesting a cardiac source of Hb. OBJECTIVE: Test the hypothesis that Hb is produced in the PMR heart and is associated with increased inflammation. METHODS AND RESULTS: Hb gene expression for subunits alpha (HBA) and beta (HBB) was assessed in right atria (RA), left atria (LA) and left ventricular (LV) tissue from donor hearts (n = 10) and PMR patient biopsies at surgery (n = 11). PMR patients (n = 22) had PCF and blood collected for macrophage markers, pro-inflammatory cytokines, and matrix metalloproteinases (MMPs). In-situ hybridization for HBA mRNA and immunohistochemistry for Hb-alpha (Hbα) and Hb-beta (Hbß) protein was performed on PMR tissue. RESULTS: HBA and HBB genes are significantly increased (>4-fold) in RA, LA, and LV in PMR vs. normal hearts. In PMR tissue, HBA mRNA is expressed in both LV cardiomyocytes and interstitial cells by in-situ hybridization; however, Hbα and Hbß protein is only expressed in interstitial cells by immunohistochemistry. PCF oxyHb is significantly increased over plasma along with low ratios (<1.0) of haptoglobin:oxyHb and hemopexin:heme supporting a highly oxidative environment. Macrophage chemotactic protein-1, tumor necrosis factor-α, interleukin-6, and MMPs are significantly higher in PCF vs. plasma. CONCLUSION: There is increased Hb production in the PMR heart coupled with the inflammatory state of the heart, suggests a myocardial vulnerability of further Hb delivery and/or production during cardiac surgery that could adversely affect LV functional recovery.

Impact of early pericardial fluid chymase activation after cardiac surgery.

Introduction: Chymase is a highly destructive serine protease rapidly neutralized in the circulation by protease inhibitors. Here we test whether pericardial fluid (PCF) chymase activation and other inflammatory biomarkers determine intensive care unit length of stay, and explore mechanisms of chymase delivery by extracellular vesicles to the heart. Methods: PCF was collected from adult patients (17 on-pump; 13 off-pump) 4 h after cardiac surgery. Extracellular vesicles (EVs) containing chymase were injected into Sprague-Dawley rats to test for their ability to deliver chymase to the heart. Results: The mean intensive care unit (ICU) stay and mean total length of stay was 2.17 ± 3.8 days and 6.41 ± 1.3 days respectively. Chymase activity and 32 inflammatory markers did not differ in on-pump vs. off-pump cardiac surgery. Society of Thoracic Surgeons Predicted Risk of Morbidity and Mortality Score (STS-PROM), 4-hour post-surgery PCF chymase activity and C-X-C motif chemokine ligand 6 (CXCL6) were all independent predictors of ICU and total hospital length of stay by univariate analysis. Mass spectrometry of baseline PCF shows the presence of serine protease inhibitors that neutralize chymase activity. The compartmentalization of chymase within and on the surface of PCF EVs was visualized by immunogold labeling and transmission electron microscopy. A chymase inhibitor prevented EV chymase activity (0.28 fmol/mg/min vs. 14.14 fmol/mg/min). Intravenous injection of PCF EVs obtained 24 h after surgery into Sprague Dawley rats shows diffuse human chymase uptake in the heart with extensive cardiomyocyte damage 4 h after injection. Discussion: Early postoperative PCF chymase activation underscores its potential role in cardiac damage soon after on- or off-pump cardiac surgery. In addition, chymase in extracellular vesicles provides a protected delivery mechanism from neutralization by circulating serine protease inhibitors.

Infusing satellite data into aerosol forecast for near real-time episode detection and diagnosis in East Asia.

A near-real-time (NRT) aerosol forecast and diagnostic approach is developed based on the system of Infusing satellite Data into Environmental Applications for East Asia, herein denoted as IDEA-EA. The design incorporates a 0.5-degree Global Forecast System (GFS) and Visible Infrared Imaging Radiometer Suite (VIIRS) aerosol and cloud retrievals for meteorological and remote sensing inputs. The primary output of IDEA-EA includes aerosol forward and backward air mass trajectory forecasts, migration visualization, and data synthesis purposed for NRT aerosol detection, monitoring, and source tracing in East Asia. Two aerosol episodes of Southeast Asia (SEA) biomass burning and Chinese haze infusion with Gobi dust are illustrated by IDEA-EA to demonstrate its forecast and source tracing capabilities. In the case of SEA biomass burning (late March 2021), forward trajectories of IDEA-EA forecasted air masses with high aerosol optical depth (AOD) from SEA affecting Taiwan. The IDEA-EA forecasts were verified by increased AOD and surface PM2.5 observations at a mountain site. In the case of the Chinese haze (October 30, 2019), backward trajectories from the northern tip of Taiwan traced air masses back to the east coast of mainland China and possibly further to the Gobi Desert. Compared with conventional numerical model simulations, the combination of the state-of-the-art aerosol remote sensing and trajectory modeling in IDEA-EA provides a cost-effective alternative for air quality management.

Plasma Exosome Hemoglobin Released During Surgery Is Associated With Cardiac Injury in Animal Model.

BACKGROUND: Patients with valvular heart disease require cardiopulmonary bypass and cardiac arrest. Here, we test the hypothesis that exosomal hemoglobin formed during cardiopulmonary bypass mediates acute cardiac injury in humans and in an animal model system. METHODS: Plasma exosomes were collected from arterial blood at baseline and 30 minutes after aortic cross-clamp release in 20 patients with primary mitral regurgitation and 7 with aortic stenosis. These exosomes were injected into Sprague-Dawley rats and studied at multiple times up to 30 days. Tissue was examined by hematoxylin and eosin stain, immunohistochemistry, transmission electron microscopy, and brain natriuretic peptide. RESULTS: Troponin I levels increased from 36 ± 88 ng/L to 3622 ± 3054 ng/L and correlated with exosome hemoglobin content (Spearman r = 0.7136, < .0001, n = 24). Injection of exosomes isolated 30 minutes after cross-clamp release into Sprague-Dawley rats resulted in cardiomyocyte myofibrillar loss at 3 days. Transmission electron microscopy demonstrated accumulation of electron dense particles of ferritin within cardiomyocytes, in the interstitial space, and within exosomes. At 21 days after injection, there was myofibrillar and myosin breakdown, interstitial fibrosis, elevated brain natriuretic peptide, and left ventricle diastolic dysfunction measured by echocardiography/Doppler. Pericardial fluid exosomal hemoglobin content is fourfold higher than simultaneous plasma exosome hemoglobin, suggesting a cardiac source of exosomal hemoglobin. CONCLUSIONS: Red blood cell and cardiac-derived exosomal hemoglobin may be involved in myocardial injury during cardiopulmonary bypass in patients with valvular heart disease.

Interstitial Collagen Loss, Myocardial Remodeling, and Function in Primary Mitral Regurgitation.

Interstitial collagen loss and cardiomyocyte ultrastructural damage accounts for left ventricular (LV) sphericity and decrease in LV twist and circumferential strain. Normal LV diastolic function belies significantly abnormal left atrial (LA) function and early LV diastolic untwist rate. This underscores the complex interplay of LV and LA myocardial remodeling and function in the pathophysiology of primary mitral regurgitation. In this study, we connect LA function with LV systolic and diastolic myocardial remodeling and function using cardiac magnetic resonance tissue tagging in primary mitral regurgitation.

Early outcomes following transatrial transcatheter mitral valve replacement in patients with severe mitral annular calcification.

OBJECTIVE: Implantation of a transcatheter valve-in-mitral annular calcification (ViMAC) has emerged as an alternative to traditional surgical mitral valve (MV) replacement. Previous studies evaluating ViMAC aggregated transseptal, transapical, and transatrial forms of the procedure, leaving uncertainty about each technique's advantages and disadvantages. Thus, we sought to evaluate clinical outcomes specifically for transatrial ViMAC from the largest multicenter registry to-date. METHODS: Patients with symptomatic MV dysfunction and severe MAC who underwent ViMAC were enrolled from 12 centers across the United States and Europe. Clinical characteristics, procedural details, and clinical outcomes were abstracted from the electronic record. The primary end point was all-cause mortality. RESULTS: We analyzed 126 patients who underwent ViMAC (median age 76 years [interquartile range {IQR}, 70-82 years], 28.6% female, median Society of Thoracic Surgeons score 6.8% [IQR, 4.0-11.4], and median follow-up 89 days [IQR, 16-383.5]). Sixty-one (48.4%) had isolated mitral stenosis, 25 (19.8%) had isolated mitral regurgitation (MR), and 40 (31.7%) had mixed MV disease. Technical success was achieved in 119 (94.4%) patients. Thirty (23.8%) patients underwent concurrent septal myectomy, and 8 (6.3%) patients experienced left ventricular outflow tract obstruction (7/8 did not undergo myectomy). Five (4.2%) patients of 118 with postprocedure echocardiograms had greater than mild paravalvular leak. Thirty-day and 1-year all-cause mortality occurred in 16 and 33 patients, respectively. In multivariable models, moderate or greater MR at baseline was associated with increased risk of 1-year mortality (hazard ratio, 2.31; 95% confidence interval, 1.07-4.99, P = .03). CONCLUSIONS: Transatrial ViMAC is safe and feasible in this selected, male-predominant cohort. Patients with significant MR may derive less benefit from ViMAC than patients with mitral stenosis only.

Hemodilution in high-risk cardiac surgery: Laboratory values, physiological parameters, and outcomes.

BACKGROUND: Acute normovolemic hemodilution (ANH) is a blood conservation strategy in cardiac surgery, predominantly used in coronary artery bypass graft (CABG) and/or valve procedures. Although higher complexity cardiac procedures may benefit from ANH, concerns for hemodynamic instability, and organ injury during hemodilution hinder its wider acceptance. Laboratory and physiological parameters during hemodilution in complex cardiac surgeries have not been described. STUDY DESIGN AND METHODS: This observational cohort (2019-2021) study included 169 patients who underwent thoracic aortic repair, multiple valve procedure, concomitant CABG with the aforementioned procedure, and/or redo sternotomies. Patients who received allogeneic blood were excluded. Statistical comparisons were performed between ANH (N = 66) and non-ANH controls (N = 103). ANH consisted of removal of blood at the beginning of surgery and its return after cardiopulmonary bypass. RESULTS: Intraoperatively, the ANH group received more albumin (p = .04) and vasopressor medications (p = .01), while urine output was no different between ANH and controls. Bilateral cerebral oximetry (rSO2 ) values were similar before and after hemodilution. During bypass, rSO2 were discretely lower in the ANH versus control group (right rSO2 p = .03, left rSO2 p = .05). No differences in lactic acid values were detected across the procedural continuum. Postoperatively, no differences in extubation times, intensive care unit length of stay, kidney injury, stroke, or infection were demonstrated. DISCUSSION: This study suggests hemodilution to be a safe and comparable blood conservation technique, even without accounting for potential benefits of reduced allogenic blood administration. The study may contribute to better understanding and wider acceptance of ANH protocols in high-risk cardiac surgeries.

Effects of acute normovolemic hemodilution on post-cardiopulmonary bypass coagulation tests and allogeneic blood transfusion in thoracic aortic repair surgery: An observational cohort study.

BACKGROUND AND AIM: Perioperative blood transfusion is associated with increased morbidity and mortality. Acute normovolemic hemodilution (ANH) is a blood conservation strategy associated with variable success, and rarely studied in more complex cardiac procedures. The study aim was to evaluate whether ANH improves coagulopathy and reduces blood transfusions in thoracic aortic surgeries. METHODS: Single-center observational cohort study comparing ANH and standard institutional practice in patients who underwent thoracic aortic repair with cardiopulmonary bypass (CPB) from 2019 to 2021. RESULTS: A total of 89 patients underwent ANH and 116 standard practice. There were no significant differences between the groups in terms of demographic or major perioperative characteristics. In the ANH group coagulation tests before and after transfusion of autologous blood showed decreased INR and increased platelets, fibrinogen, all with p < 0.0005. Coagulation results in the ANH and control groups were not statistically different. The average number of transfused allogeneic products per patient was lower in the ANH versus control group: FFP 1.1 ± 1.6 versus 1.9 ± 2.3 (p = 0.003), platelets 0.6 ± 0.8 versus 1.2 ± 1.3 (p = 0.0008), and cryoprecipitate 0.3 ± 0.7 versus 0.7 ± 1.1 (p = 0.008). Reduction in red blood cell transfusion was not statistically significant. The percentage of patients who received any transfusion was 53.9% in ANH and 59.5% in the control group (p = 0.42). There was no significant difference in major adverse outcomes. CONCLUSIONS: ANH is a safe blood conservation strategy for surgical repairs of the thoracic aorta. Laboratory data suggests ANH can improve some coagulation values after separation from CPB, and significantly reduce the number of transfused FFP, platelets and cryoprecipitate.

Coronary artery bypass graft surgery outcomes in the United States: Impact of the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: There has been a substantial decline in patients presenting for emergent and routine cardiovascular care in the United States after the onset of the coronavirus disease 2019 (COVID-19) pandemic. We sought to assess the risk of adverse clinical outcomes among patients undergoing coronary artery bypass graft (CABG) surgery during the 2020 COVID-19 pandemic period and compare the risks with those undergoing CABG before the pandemic in the year 2019. METHODS: A retrospective cross-sectional analysis of the TriNetX Research Network database was performed. Patients undergoing CABG between January 20, 2019, and September 15, 2019, contributed to the 2019 cohort, and those undergoing CABG between January 20, 2020, and September 15, 2020, contributed to the 2020 cohort. Propensity-score matching was performed, and the odds of mortality, acute kidney injury, stroke, acute respiratory distress syndrome, and mechanical ventilation occurring by 30 days were evaluated. RESULTS: The number of patients undergoing CABG in 2020 declined by 35.5% from 5534 patients in 2019 to 3569 patients in 2020. After propensity-score matching, 3569 patient pairs were identified in the 2019 and the 2020 cohorts. Compared with those undergoing CABG in 2019, the odds of mortality by 30 days were 0.96 (95% confidence interval [CI], 0.69-1.33; P = .80) in those undergoing CABG in 2020. The odds for stroke (odds ratio [OR], 1.201; 95% CI, 0.96-1.39), acute kidney injury (OR, 0.76; 95% CI, 0.59-1.08), acute respiratory distress syndrome (OR, 1.01; 95% CI, 0.60-2.42), and mechanical ventilation (OR, 1.11; 95% CI, 0.94-1.30) were similar between the 2 cohorts. CONCLUSIONS: The number of patients undergoing CABG in 2020 has substantially declined compared with 2019. Similar odds of adverse clinical outcomes were seen among patients undergoing CABG in the setting of COVID-19 compared with those in 2019.

Cardiac Surgery and Postoperative Renal Allograft Failure.

BACKGROUND: Although cardiac surgery among renal allograft recipients is relatively safe, less is known about the impact of cardiac surgery on the functioning renal allograft. This study assessed postoperative renal failure among renal transplant recipients undergoing cardiac surgery. METHODS: The study population was identified by matching medical record numbers from the United Network for Organ Sharing Kidney Transplant Database to a cardiovascular surgery database and The Society of Thoracic Surgeons Adult Cardiac Surgery Database for the authors' institution from January 1992 through August 2018. RESULTS: One hundred seventy-nine renal transplant recipients with a functioning allograft underwent cardiac surgery a mean of 6.4 ± 5.6 years after renal transplantation. Thirty (17.6%) of the 170 patients either died or had allograft failure during the first postoperative year. Receiver-operating characteristics curve analysis using Cox regression demonstrated an optimal cutoff point for preoperative serum creatinine predicting postoperative allograft loss is 1.9 mg/dL (hazard ratio 3; 95% confidence interval, 1.5 to 6.9) with a model C statistic of 0.642. CONCLUSIONS: The current study affirms findings in the literature that cardiac surgery in renal transplant recipients carries acceptable perioperative morbidity and mortality. Renal transplant recipients who underwent cardiac surgery had a constant hazard of renal allograft loss similar to that of the general transplant population. A preoperative serum creatinine value greater than 1.9 mg/dL increases the risk for long-term renal allograft loss after cardiac surgery.

Robotic mitral valve repair in a type B hemophiliac.

Hemophilia B is a rare X-linked recessive disorder that places surgical patients at an increased risk of bleeding. Patients with hemophilia are now achieving near-normal life expectancies and therefore the number of these patients requiring cardiac surgery due to the development of age-related cardiovascular disease may increase. We present the case of a young male with hemophilia B who was diagnosed with severe symptomatic mitral regurgitation and underwent successful robotic mitral valve repair. To our knowledge, this is the first report of a patient with hemophilia B who underwent robotic mitral valve repair.

Reduced Left Atrial Emptying Fraction and Chymase Activation in Pathophysiology of Primary Mitral Regurgitation.

Increasing left atrial (LA) size predicts outcomes in patients with isolated mitral regurgitation (MR). Chymase is plentiful in the human heart and affects extracellular matrix remodeling. Chymase activation correlates to LA fibrosis, LA enlargement, and a decreased total LA emptying fraction in addition to having a potential intracellular role in mediating myofibrillar breakdown in LA myocytes. Because of the unreliability of the left ventricular ejection fraction in predicting outcomes in MR, LA size and the total LA emptying fraction may be more suitable indicators for timing of surgical intervention.

Best Practices of Aortic Valve Replacement With the Edwards Intuity Elite Valve.

PURPOSE: The Edwards Intuity Elite (EIE; Edwards Lifesciences, Irvine, CA) valve system is a recent surgical aortic valve designed to expedite implantation, facilitate minimally invasive approaches, and provide low gradients, particularly in smaller valve sizes. The report reviews various best practices learned through experience with the EIE valve system. DESCRIPTION: With its sealing frame designed to anchor and seal the valve after resection of the diseased native aortic valve, EIE use differs from that of conventional sutured valves. EVALUATION: Critical technical aspects include patient selection, aortotomy and debridement, valve sizing, guiding suture technique and valve seating and deployment. In addition, special anatomic and pathologic conditions are considered, as well as intraoperative transesophageal echocardiography and postimplantation cardiac rhythm monitoring. CONCLUSIONS: These best practices simplify and standardize the use of the EIE valve system and may benefit surgeons adopting this valve.

'New Medicine Service': supporting adherence in people starting a new medication for a long-term condition: 26-week follow-up of a pragmatic randomised controlled trial.

OBJECTIVE: To examine the effectiveness and cost-effectiveness of the community pharmacy New Medicine Service (NMS) at 26 weeks. METHODS: Pragmatic patient-level parallel randomised controlled trial in 46 English community pharmacies. 504 participants aged ≥14, identified in the pharmacy when presenting a prescription for a new medicine for predefined long-term conditions, randomised to receive NMS (n=251) or normal practice (n=253) (NMS intervention: 2 consultations 1 and 2 weeks after prescription presentation). Adherence assessed through patient self-report at 26-week follow-up. Intention-to-treat analysis employed. National Health Service (NHS) costs calculated. Disease-specific Markov models estimating impact of non-adherence combined with clinical trial data to calculate costs per extra quality-adjusted life-year (QALY; NHS England perspective). RESULTS: Unadjusted analysis: of 327 patients still taking the initial medicine, 97/170 (57.1%) and 103/157 (65.6%) (p=0.113) patients were adherent in normal practice and NMS arms, respectively. Adjusted intention-to-treat analysis: adherence OR 1.50 (95% CI 0.93 to 2.44, p=0.095), in favour of NMS. There was a non-significant reduction in 26-week NHS costs for NMS: -£104 (95% CI -£37 to £257, p=0.168) per patient. NMS generated a mean of 0.04 (95% CI -0.01 to 0.13) more QALYs per patient, with mean reduction in lifetime cost of -£113.9 (-1159.4, 683.7). The incremental cost-effectiveness ratio was -£2758/QALY (2.5% and 97.5%: -38 739.5, 34 024.2. NMS has an 89% probability of cost-effectiveness at a willingness to pay of £20 000 per QALY. CONCLUSIONS: At 26-week follow-up, NMS was unable to demonstrate a statistically significant increase in adherence or reduction in NHS costs, which may be attributable to patient attrition from the study. Long-term economic evaluation suggested NMS may deliver better patient outcomes and reduced overall healthcare costs than normal practice, but uncertainty around this finding is high. TRIAL REGISTRATION NUMBER: NCT01635361, ISRCTN23560818, ISRCTN23560818, UKCRN12494.

Left ventricular myxoma: A contractile mass causing intracavitary obstruction and severe pulmonary hypertension.

Cardiac myxomas can be fatal and left ventricular (LV) myxomas with papillary muscle and mitral valve (MV) involvement are rare. The following case is that of a 55-year-old woman who developed signs and symptoms of pulmonary hypertension. Imaging revealed a contractile mass in the LV that was in continuum with the papillary muscles and affected MV function. Her clinical course, radiologic, and hemodynamic findings are discussed. Finally, her surgical extraction technique is described in addition to potential complications encountered.