Advancing cardiotomy suction practices for coronary surgery via multidisciplinary collaborative learning.

Objective: Professional standards recommend stopping cardiotomy suction at the termination of cardiopulmonary bypass before protamine administration based on perceived safety concerns. This study evaluated a multidisciplinary collaborative quality-improvement intervention promoting this agreed-upon cardiotomy suction practice during coronary artery bypass grafting (CABG). Methods: A statewide intervention (eg, unblinded surgeon and perfusionist feedback, evidence-based lectures, evaluating barriers to change) involved 32 centers participating in the PERForm (ie, Perfusion Measures and Outcomes) Registry to standardize cardiotomy suction practices at cardiopulmonary bypass termination during CABG. Four non-Michigan registry participating centers were not exposed to collaborative learning. Cardiotomy suction practice was defined as the absence of or stopping cardiotomy suction before protamine administration. The practice changes attributed to the intervention, including Michigan and non-Michigan comparisons, were evaluated with the change of time effect modeled using splines. Multivariable regression was used to evaluate the intervention's associated impact (eg, mortality, reoperation, transfusion). Results: Among 10,394 patients undergoing CABG at Michigan centers, 80.7% achieved agreed-upon cardiotomy suction practices. The Michigan centers had nonsignificant changes in agreed-upon cardiotomy suction practices during the preintervention period (P = .24), with significant increased monthly change in practice thereafter, absent adjusted morbidity and mortality increases. The Michigan centers achieved a significantly greater adjusted monthly improvement in agreed-upon practices relative to non-Michigan centers within 7 months after the intervention (adjusted odds ratio for change of trends: 2.53, P < .001). Conclusions: This initiative demonstrates the effectiveness of multidisciplinary collaborative quality improvement in advancing agreed-upon cardiotomy suction practices without negatively impacting clinical outcomes.

Heart-Lung Transplantation From Donation After Circulatory Death Using Mobile Normothermic Regional Perfusion.

Combined heart-lung transplant (HTLx) is the most durable treatment available for end-stage heart and lung failure. Many patients are unable to receive combined organs due to organ availability and allocation policies prioritizing separate heart or lung transplantation. While an average of 45 HTLxs have been performed per year in the United States half the listed patients do not receive organs. Recently, donation after circulatory death (DCD) utilizing normothermic regional perfusion (NRP) has been utilized for heart allografts with excellent results, and here, we present a case utilizing mobile NRP to procure a heart and lung block from a circulatory death donor and successful implantation for a recipient in a separate center.

Phylogeny of Crataegus (Rosaceae) based on 257 nuclear loci and chloroplast genomes: evaluating the impact of hybridization.

BACKGROUND: Hawthorn species (Crataegus L.; Rosaceae tribe Maleae) form a well-defined clade comprising five subgeneric groups readily distinguished using either molecular or morphological data. While multiple subsidiary groups (taxonomic sections, series) are recognized within some subgenera, the number of and relationships among species in these groups are subject to disagreement. Gametophytic apomixis and polyploidy are prevalent in the genus, and disagreement concerns whether and how apomictic genotypes should be recognized taxonomically. Recent studies suggest that many polyploids arise from hybridization between members of different infrageneric groups. METHODS: We used target capture and high throughput sequencing to obtain nucleotide sequences for 257 nuclear loci and nearly complete chloroplast genomes from a sample of hawthorns representing all five currently recognized subgenera. Our sample is structured to include two examples of intersubgeneric hybrids and their putative diploid and tetraploid parents. We queried the alignment of nuclear loci directly for evidence of hybridization, and compared individual gene trees with each other, and with both the maximum likelihood plastome tree and the nuclear concatenated and multilocus coalescent-based trees. Tree comparisons provided a promising, if challenging (because of the number of comparisons involved) method for visualizing variation in tree topology. We found it useful to deploy comparisons based not only on tree-tree distances but also on a metric of tree-tree concordance that uses extrinsic information about the relatedness of the terminals in comparing tree topologies. RESULTS: We obtained well-supported phylogenies from plastome sequences and from a minimum of 244 low copy-number nuclear loci. These are consistent with a previous morphology-based subgeneric classification of the genus. Despite the high heterogeneity of individual gene trees, we corroborate earlier evidence for the importance of hybridization in the evolution of Crataegus. Hybridization between subgenus Americanae and subgenus Sanguineae was documented for the origin of Sanguineae tetraploids, but not for a tetraploid Americanae species. This is also the first application of target capture probes designed with apple genome sequence. We successfully assembled 95% of 257 loci in Crataegus, indicating their potential utility across the genera of the apple tribe.

Evaluating Changes in del Nido Cardioplegia Practices in Adult Cardiac Surgery.

There has been a rapid adoption of the use of del Nido cardioplegia (DC) among adults undergoing cardiac surgery. We leveraged a multicenter database to evaluate differences over time in the choice and impact of cardioplegia type (DC vs. blood) among patients undergoing cardiac surgery. We evaluated 26,373 patients undergoing non-emergent coronary artery bypass and/or valve surgery between 2014-2015 (early period) and 2017-2018 (late period) at 31 centers. DC was compared with blood-based cardioplegia (BC: 1:1, 2:1, 4:1, 8:1, and variable ratio). We evaluated whether treatment choice differed across prespecified patient characteristics, procedure type, and perfusion practices by time period. We evaluated increased DC use with clinical outcomes (major morbidity and mortality, prolonged intubation, and renal failure), after adjusting for baseline characteristics, procedure type, center, and year. DC use increased from 19.6% in 2014-2015 to 41.5% in 2017-2018, p < .001. Increased DC use occurred among coronary artery bypass grafting (CABG), valve, and CABG + valve procedures, all p < .001. Differences in median procedural duration increased over time (DC vs. BC): 1) bypass duration was 11.0 minutes shorter with DC in the early period and 27.0 minutes shorter in the late period, and 2) cross-clamp duration was 7.0 minutes shorter with DC in the early period and 17.0 minutes shorter in the late period, all p < .001. There were no statistical differences in adjusted odds of major morbidity and mortality (odds ratio [OR]adj: 1.01), prolonged intubation (ORadj: .99), or renal failure (ORadj: .80) by DC use (p > .05). In this large multicenter experience, DC use increased over time and was associated with reduced bypass and ischemic time absent any significant differences in adjusted outcomes.

Effect of sex on nadir hematocrit and rates of acute kidney injury in coronary artery bypass.

OBJECTIVE: Findings from a large multicenter experience showed that sex influenced the relationship between low nadir hematocrit and increased risk of acute kidney injury after cardiac surgery. We explored whether sex-related differences persisted among patients undergoing isolated coronary artery bypass grafting. METHODS: We undertook a prospective, observational study of 17,363 patients without dialysis (13,137 male: 75.7%; 4226 female: 24.3%) undergoing isolated coronary artery bypass grafting between 2011 and 2016 across 41 institutions in the Perfusion Measures and Outcomes registry. Odds ratios between nadir hematocrit and stage 2 or 3 acute kidney injury were calculated, and the interaction of sex with nadir hematocrit was tested. The multivariable, generalized, linear mixed-effect model adjusted for preoperative and intraoperative factors and institution. RESULTS: Median nadir hematocrit was 22% among women and 27% among men (P < .001). Women were administered a greater median net prime volume indexed to body surface area (407 vs 363 mL/m2) and more red blood cell transfusions (55.5% vs 24.3%; both P < .001). Acute kidney injury was higher among women (6.0% vs 4.3%, P < .001). There was no effect of sex on the relationship between nadir hematocrit and acute kidney injury (P = .67). Low nadir hematocrit was inversely associated with acute kidney injury (adjusted odds ratios per 1-unit increase in nadir hematocrit 0.96; 95% confidence interval, 0.93-0.98); this effect was similar across sexes and independent of red blood cell transfusions. CONCLUSIONS: We found no sex-related differences in the effect of nadir hematocrit on acute kidney injury after isolated coronary artery bypass grafting. However, the strong inverse relationship between anemia and acute kidney injury across sexes suggests the importance of reducing exposure to low nadir hematocrit.

Net Prime Volume Is Associated with Increased Odds of Blood Transfusion.

Hemodilutional anemia has been cited as a contributing factor to red blood cell (RBC) transfusions in cardiac surgery patients. Accordingly, efforts have been made to minimize hemodilution by reducing cardiopulmonary bypass (CPB) prime volume. We sought to assess the impact of these efforts on intraoperative RBC transfusions. We evaluated 21,360 patients undergoing coronary artery bypass with or without aortic valve surgery between July 2011 through December 2016 at any of 42 centers participating in the Perfusion Measures and Outcomes registry. The primary exposure was net CPB prime volume (total prime volume minus retrograde autologous prime volume) indexed to body surface area (mL/m2), which was further divided into quartiles (Q1: <262 mL/m2, Q2: 262-377 mL/m2, Q3: 377-516 mL/m2, and Q4: >516 mL/m2). The primary outcome was intraoperative RBC transfusion. We modeled the effect of index net prime volume on transfusion, adjusting for patient (age, gender, race, diabetes, vascular disease, previous myocardial infarction, ejection fraction, creatinine, preoperative hematocrit (HCT), total albumin, status, aspirin, and antiplatelet agents), procedural (procedure types) characteristics, surgical year, and hospital. The median net prime volume was 378 mL/m2 (25th percentile: 262 mL/m2, 75th percentile: 516 mL/m2). Relative to patients in Q1, patients in Q4 were more likely to be older, female, nondiabetic, have higher ejection fraction, have more ultrafiltration volume removed, and undergo more elective and aortic valve procedures (all p < .05). Patients in Q4 relative to Q1 were exposed to lower nadir HCTs on bypass, p < .05. The net prime volume was associated with an increased risk of transfusion (8.9% in Q1 vs. 22.6% in Q4, p < .001). After adjustment, patients in Q4 (relative to Q1) had a 2.9-fold increased odds (ORadj = 2.9, 95% CI [2.4, 3.4]) of intraoperative RBC transfusion. In this large, multicenter experience, patients exposed to larger net prime volumes were associated with greater adjusted odds of receiving intraoperative transfusions. Our findings reinforce the importance of efforts to reduce the net CPB prime volume. Based on these findings and other supporting evidence, the net prime volume should be adopted as a national quality measure.

Is Conventional Bypass for Coronary Artery Bypass Graft Surgery a Misnomer?

Although recent trials comparing on vs. off-pump revascularization techniques describe cardiopulmonary bypass (CPB) as "conventional," inadequate description and evaluation of how CPB is managed often exist in the peer-reviewed literature. We identify and subsequently describe regional and center-level differences in the techniques and equipment used for conducting CPB in the setting of coronary artery bypass grafting (CABG) surgery. We accessed prospectively collected data among isolated CABG procedures submitted to either the Australian and New Zealand Collaborative Perfusion Registry (ANZCPR) or Perfusion Measures and outcomes (PERForm) Registry between January 1, 2014, and December 31, 2015. Variation in equipment and management practices reflecting key areas of CPB is described across 47 centers (ANZCPR: 9; PERForm: 38). We report average usage (categorical data) or median values (continuous data) at the center-level, along with the minimum and maximum across centers. Three thousand five hundred sixty-two patients were identified in the ANZCPR and 8,450 in PERForm. Substantial variation in equipment usage and CPB management practices existed (within and across registries). Open venous reservoirs were commonly used across both registries (nearly 100%), as were "all-but-cannula" biopassive surface coatings (>90%), whereas roller pumps were more commonly used in ANZCPR (ANZCPR: 85% vs. PERForm: 64%). ANZCPR participants had 640 mL absolute higher net prime volumes, attributed in part to higher total prime volume (1,462 mL vs. 1,217 mL) and lower adoption of retrograde autologous priming (20% vs. 81%). ANZCPR participants had higher nadir hematocrit on CPB (27 vs. 25). Minimal absolute differences existed in exposure to high arterial outflow temperatures (36.6°C vs. 37.0°C). We report substantial center and registry differences in both the type of equipment used and CPB management strategies. These findings suggest that the term "conventional bypass" may not adequately reflect real-world experiences. Instead of using this term, authors should provide key details of the CPB practices used in their patients.

A BMI >35 does not protect patients undergoing cardiac bypass surgery from red blood cell transfusion.

The effect of obesity on allogeneic intraoperative blood product transfusion in patients undergoing coronary artery bypass graft surgery (CABG) is poorly understood. We analyzed the influence of obesity on the risk of intraoperative red blood cell (RBC) transfusion among 45,200 consecutive non-reoperative CABG procedures from a multi-institutional perfusion database. A body mass index (BMI) in obese I category was associated with a 9.9% decrease in transfusion risk (p<0.05). Compared to patients with a normal BMI, obese I and obese III patients do not have any change in the relative risk of RBC transfusion. Overweight and mild obesity have a protective role in reducing intraoperative blood transfusion during cardiopulmonary bypass (CPB) surgery. However, logistic regression analysis showed that much of the observed reduction in transfusion rates for obese patients can be accounted for by other known confounds. The lack of a linear effect of increasing BMI on blood transfusion risk is a novel finding and warrants further investigation.

Using herbarium-derived DNAs to assemble a large-scale DNA barcode library for the vascular plants of Canada.

PREMISE OF THE STUDY: Constructing complete, accurate plant DNA barcode reference libraries can be logistically challenging for large-scale floras. Here we demonstrate the promise and challenges of using herbarium collections for building a DNA barcode reference library for the vascular plant flora of Canada. METHODS: Our study examined 20,816 specimens representing 5076 of 5190 vascular plant species in Canada (98%). For 98% of the specimens, at least one of the DNA barcode regions was recovered from the plastid loci rbcL and matK and from the nuclear ITS2 region. We used beta regression to quantify the effects of age, type of preservation, and taxonomic affiliation (family) on DNA sequence recovery. RESULTS: Specimen age and method of preservation had significant effects on sequence recovery for all markers, but influenced some families more (e.g., Boraginaceae) than others (e.g., Asteraceae). DISCUSSION: Our DNA barcode library represents an unparalleled resource for metagenomic and ecological genetic research working on temperate and arctic biomes. An observed decline in sequence recovery with specimen age may be associated with poor primer matches, intragenomic variation (for ITS2), or inhibitory secondary compounds in some taxa.

Prediction of Transfusions After Isolated Coronary Artery Bypass Grafting Surgical Procedures.

BACKGROUND: Although blood transfusions are common and have been associated with adverse sequelae after cardiac surgical procedures, few contemporaneous models exist to support clinical decision making. This study developed a preoperative clinical decision support tool to predict perioperative red blood cell transfusions in the setting of isolated coronary artery bypass grafting. METHODS: We performed a multicenter, observational study of 20,377 patients undergoing isolated coronary artery bypass grafting among patients at 39 hospitals participating in the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative's PERFusion measures and outcomes (PERForm) registry between 2011 and 2015. Candidates' preoperative risk factors were identified based on previous work and clinical input. The study population was randomly divided into a 70% development sample and a 30% validation sample. A generalized linear mixed-effect model was developed to predict perioperative red blood cell transfusion. The model's performance was assessed for calibration and discrimination. Sensitivity analysis was performed to assess the robustness of the model in different clinical subgroups. RESULTS: Transfusions occurred in 36.8% of patients. The final regression model included 16 preoperative variables. The correlation between the observed and expected transfusions was 1.0. The risk prediction model discriminated well (receiver operator characteristic [ROC]development, 0.81; ROCvalidation, 0.82) and had satisfactory calibration (correlation between observed and expected rates was r = 1.00). The model performance was confirmed across medical centers and clinical subgroups. CONCLUSIONS: Our risk prediction model uses 16 readily obtainable preoperative variables. This model, which provides a patient-specific estimate of the need for transfusion, offers clinicians a guide for decision making and evaluating the effectiveness of blood management strategies.

The Unintended Consequences of Over-Reducing Cardiopulmonary Bypass Circuit Prime Volume.

BACKGROUND: The Society of Thoracic Surgeon blood conservation guidelines recommend minimizing cardiopulmonary bypass circuit prime volume (PV) as an integral, evidence-based (Class I, Level A) blood conservation strategy. We used a large, multiinstitutional registry to evaluate the effectiveness of restricting cardiopulmonary bypass PV on intraoperative red blood cell (RBC) transfusion. METHODS: We reviewed 47,273 isolated coronary artery bypass graft procedures performed among 189 institutions between April 2012 and May 2015. The primary outcome was intraoperative transfusion of at least 1 unit RBC; the secondary outcome was intraoperative transfusion of 4 or more units RBC. We estimated the adjusted odds of each transfusion type using separate multivariable logistic regression models that controlled for 13 confounding factors. The effect of PV on odds of transfusion was modeled using restricted cubic splines to assess possible nonlinearity. RESULTS: We found a statistically significant nonlinear pattern in the relation between PV and odds of transfusion of both 1 or more units RBC (χ2 = 116.3, df = 4, p < 0.001) and 4 or more units RBC (χ2 = 25.9, df = 4, p < 0.001). The lowest probability of transfusion of 1 or more units RBC was estimated at a ratio of PV to estimated blood volume of 0.152 (p < 0.001). CONCLUSIONS: Efforts to minimize PV below 15% of a patient's estimated blood volume do not protect patients from intraoperative RBC transfusion, and may increase exposure. Prime volume can affect both patient morbidity and the economic impact associated with blood utilization. Further studies on the effect of PV on blood transfusion are warranted.

The Relationship between Intra-Operative Transfusions and Nadir Hematocrit on Post-Operative Outcomes after Cardiac Surgery.

Uncertainty exists regarding the optimal strategy for the management of anemia in the setting of cardiac surgery. We sought to improve our understanding of the role of intra-operative hematocrit (HCT) and transfusions on peri-operative outcomes following cardiac surgery. A total of 18,886 patients undergoing on-pump cardiac surgery were identified from a multi-institutional registry including surgical and perfusion data. Patients were divided into four groups based on their intra-operative nadir HCT (<21 or ≥21) and whether or not they received intra-operative red blood cell (+RBC or -RBC) transfusions. Outcomes were adjusted for the Society of Thoracic Surgeons predicted risk of mortality (PROM), pre-operative HCT, and medical center. Regardless of nadir HCT cohort, those who received a transfusion had higher PROM relative to patients who did not receive a transfusion. The mean PROM was significantly higher among those HCT ≥21 + RBC (5.3%) vs. HCT ≥ 21 - RBC (1.9%), p < .001. Similarly, the PROM was significantly higher among HCT <21 + RBC (5.1%) vs. those HCT <21 - RBC (3.1%), p < .001. Adjusted outcomes demonstrated an increased impact of RBC transfusions on adverse outcomes irrespective of nadir HCT including stroke (p < .001), renal failure (p < .001), prolonged ventilation (p < .001), and mortality (p < .001). This study demonstrates that transfusions have a more profound effect on post-operative cardiac surgery outcomes than anemia.

Blood Conservation-A Team Sport.

Cardiac surgery accounts for between 15% and 20% of all blood product utilization in the United States. A body of literature suggests that patients who are exposed to even small quantities of blood have an increased risk of morbidity and mortality, even after adjusting for pre-operative risk. Despite this body of literature supporting a restrictive blood management strategy, wide variability in transfusion rates exist across institutions. Recent blood management guidelines have shed light on a number of potentially promising blood management strategies, including acute normovolemic hemodilution (ANH) and retrograde autologous priming (RAP). We evaluated the literature concerning ANH and RAP, and the use of both techniques among centers participating in the Perfusion Measures and outcomes (PERForm) registry. We leveraged data concerning ANH and RAP among 10,203 patients undergoing isolated coronary artery bypass grafting (CABG) procedures from 2010 to 2014 at 27 medical centers. Meta-analyses have focused on the topic of ANH, with few studies focusing specifically on cardiac surgery. Two meta-analyses have been conducted to date on RAP, with many reporting higher intra-operative hematocrits and reduced transfusions. The rate of red blood cell transfusions in the setting of CABG surgery is 34.2%, although varied across institutions from 16.8% to 57.6%. Overall use of ANH was 11.6%, although the utilization varied from .0% to 75.7% across institutions. RAP use was 71.4%, although varied from .0% to 99.0% across institutions. A number of blood conservation strategies have been proposed, with varying levels of evidence from meta-analyses. This uncertainty has likely contributed to center-level differences in the utilization of these practices as evidenced by our multi-institutional database. Perfusion databases, including the PERForm registry, serve as a vehicle for perfusionist's to track their practice, and contribute to multidisciplinary team efforts aimed at assessing and improving the value of cardiac surgical care.

Hypolipidemic and cardioprotective benefits of a novel fireberry hawthorn fruit extract in the JCR:LA-cp rodent model of dyslipidemia and cardiac dysfunction.

Hawthorn is a widely used herbal alternative medicine for the treatment of various cardiovascular diseases. However, the attributed health benefits, purported to be due to the presence of phenolic compounds, may depend on both the specific species and plant part. Studies to date investigating effects of hawthorn on heart disease(s) have used well-described European and/or Asian species, while little is known regarding the bioactivity of species native to North America. Six weeks of supplementation of both fireberry hawthorn berry (native Crataegus chrysocarpa) and English hawthorn leaf (C. monogyna, naturalized in North America) in the JCR:LA-cp rat, resulted in a significant reduction in heart weight, fasting LDL-C and improved heart function (p < 0.05). Fasting triglyceride and myocardial fibrosis were also reduced, but only by the berry extract. We demonstrate that both of the Canadian-sourced hawthorn extracts (introduced leaf and native berry) have cardioprotective benefits, likely via increased availability of nitric oxide.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management during Cardiopulmonary Bypass.

To improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendation.

Report from AmSECT's International Consortium for Evidence- Based Perfusion Consensus Statement: Minimal Criteria for Reporting Cardiopulmonary Bypass-Related Contributions to Red Blood Cell Transfusions Associated With Adult Cardiac Surgery.

Gaps remain in our understanding of the contribution of bypass-related practices associated with red blood cell (RBC) transfusions after cardiac surgery. Variability exists in the reporting of bypass-related practices in the peer-reviewed literature. In an effort to create uniformity in reporting, a draft statement outlining proposed minimal criteria for reporting cardiopulmonary bypass (CPB)- related contributions (i.e., RBC data collection/documentation, clinical considerations for transfusions, equipment details, and clinical endpoints) was presented in conjunction with the American Society of ExtraCorporeal Technology's (AmSECT's) 2014 Quality and Outcomes Meeting (Baltimore, MD). Based on presentations and feedback from the conference, coauthors (n = 14) developed and subsequently voted on each proposed data element. Data elements receiving a total of 4 votes were dropped from further consideration, 5-9 votes were considered as "Recommended," and elements receiving ≥10 votes were considered as "Mandatory." A total of 52 elements were classified as mandatory, 16 recommended, and 14 dropped. There are 8 mandatory data elements for RBC data collection/documentation, 24 for clinical considerations for transfusions, 13 for equipment details, and 7 for clinical endpoints. We present 52 mandatory data elements reflecting CPB-related contributions to RBC transfusions. Consistency of such reporting would offer our community an increased opportunity to shed light on the relationship between intra-operative practices and RBC transfusions.