Enhanced Telehealth Home-Monitoring Intervention for Vulnerable and Frail Patients after Cardiac Surgery (THE-FACS Pilot Intervention Study).

BACKGROUND: Frail cardiac surgery patients have an increased risk of worse postoperative outcomes. The purpose of this study was to evaluate the implementation of a novel Telehealth Home monitoring Enhanced-Frailty And Cardiac Surgery (THE-FACS) intervention and determine its impact on clinical outcomes in frail patients post-cardiac surgery. METHODS: Frail/vulnerable patients defined by Edmonton Frailty Scale (EFS > 4) undergoing cardiac surgery were prospectively enrolled (November 2019 -March 2020) at the New Brunswick Heart Centre. Exclusion criteria included age < 55 years, emergent status, minimally invasive surgery, lack of home support, and > 10-days postoperative hospital stay. Following standard training on THE-FACS, participants were sent home with a tablet device to answer questions about their health/recovery and measure blood pressure for 30-consecutive days. Transmitted data were monitored by trained cardiac surgery follow-up nurses. Patients were contacted only if the algorithm based on the patient's self-collected data triggered an alert. Patients who completed the study were compared to historical controls. The primary outcome of interest was to determine the number of patients that could complete THE-FACS; secondary outcomes included participant/caregiver satisfaction and impact on hospital readmission. RESULTS: We identified 86 eligible (EFS > 4), out of 254 patients scheduled for elective cardiac surgery during the study period (vulnerable: 34%). The patients who consented to participate in THE-FACS (64/86, 74%) had a mean age of 69.1 ± 6.4 years, 25% were female, 79.7% underwent isolated Coronary Artery Bypass Graft (CABG) and median EFS was 6 (5-8). 29/64 (45%) were excluded post-enrollment due to prolonged hospitalization (15/64) or requirement for hospital-to-hospital transfer (12/64). Of the remaining 35 patients, 21 completed the 30-day follow-up (completion rate:60%). Reasons for withdrawal (14/35, 40%) were mostly due to technical difficulties with the tablet. Hospital readmission, although non-significant, was reduced in THE-FACS participants compared to controls (0% vs. 14.3%). A satisfaction survey revealed > 90% satisfaction and ~ 67% willingness to re-use a home monitoring device. CONCLUSIONS: THE-FACS intervention can be used to successfully monitor vulnerable patients returning home post-cardiac surgery. However, a significant number of frail patients could not benefit from THE-FACS given prolonged hospitalization and technological challenges. Our findings suggest that despite overall excellent satisfaction in participants who completed THE-FACS, there remain major challenges for wide-scale implementation of technology-driven home monitoring programs as only 24% completed the study.

Cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care and cardiac surgery. We report cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic. METHODS: A detailed survey was sent to recruit participating adult cardiac surgery centers in North America. Data regarding cardiac surgeons' perceptions and changes in practice were analyzed. RESULTS: Our study comprises 67 institutions with diverse geographic distribution across North America. Nurses were most likely to be redeployed (88%), followed by advanced care practitioners (69%), trainees (28%), and surgeons (25%). Examining surgeon concerns in regard to COVID-19, they were most worried with exposing their family to COVID-19 (81%), followed by contracting COVID-19 (68%), running out of personal protective equipment (PPE) (28%), and hospital resources (28%). In terms of PPE conservation strategies among users of N95 respirators, nearly half were recycling via decontamination with ultraviolet light (49%), followed by sterilization with heat (13%) and at home or with other modalities (13%). Reuse of N95 respirators for 1 day (22%), 1 week (21%) or 1 month (6%) was reported. There were differences in adoption of methods to conserve N95 respirators based on institutional pandemic phase and COVID-19 burden, with higher COVID-19 burden institutions more likely to resort to PPE conservation strategies. CONCLUSIONS: The present study demonstrates the impact of COVID-19 on North American cardiac surgeons. Our study should stimulate further discussions to identify optimal solutions to improve workforce preparedness for subsequent surges, as well as facilitate the navigation of future healthcare crises.

Increased mast cell density is associated with decreased fibrosis in human atrial tissue.

Fibrotic remodelling of the atria is poorly understood and can be regulated by myocardial immune cell populations after injury. Mast cells are resident immune sentinel cells present in the heart that respond to tissue damage and have been linked to fibrosis in other settings. The role of cardiac mast cells in fibrotic remodelling in response to human myocardial injury is controversial. In this study, we sought to determine the association between mast cells, atrial fibrosis, and outcomes in a heterogeneous population of cardiac surgical patients, including a substantial proportion of coronary artery bypass grafting patients. Atrial appendage from patients was assessed for collagen and mast cell density by histology and by droplet digital polymerase chain reaction (ddPCR) for mast cell associated transcripts. Clinical variables and outcomes were also followed. Mast cells were detected in human atrial tissue at varying densities. Histological and ddPCR assessment of mast cells in atrial tissue were closely correlated. Patients with high mast cell density had less fibrosis and lower severity of heart failure classification or incidence mortality than patients with low mast cell content. Analysis of a homogeneous population of coronary artery bypass graft patients yielded similar observations. Therefore, evidence from this study suggests that increased atrial mast cell populations are associated with decreased clinical cardiac fibrotic remodelling and improved outcomes, in cardiac surgery patients.

The prophylactic use of fibrinogen concentrate in high-risk cardiac surgery.

BACKGROUND: Perioperative blood loss is a major contributor to morbidity and mortality in cardiac surgery. Plasma fibrinogen levels play an essential role in hemostasis and deplete quickly during hemorrhage. The objective of this study was to determine whether prophylactic fibrinogen concentrate administration lowers overall blood product transfusion requirements in high-risk cardiac surgery in patients with low fibrinogen plasma levels. METHODS: The study was performed in a prospective, randomized, and double-blinded design. The investigation included 62 patients undergoing elective, high-risk cardiac surgery. After weaning from cardiopulmonary bypass and reversal of heparin patients received either fibrinogen concentrate or placebo. The primary outcome variable was overall blood product usage 24 hours after intervention. RESULTS: The fibrinogen group received numerically fewer total units of blood products than the placebo group, but the difference was not statistically or clinically significant (for groups n = 27; n = 29 and 19 vs 37 units, respectively, P = .908). The overall transfusion rate in both groups was significantly lower than the institutional average suggested (fibrinogen group 26%, placebo group 28%). The fibrinogen group showed significantly higher fibrinogen levels (2.38 vs 1.83 g/L (end of surgery), P < .001; 3.33 vs 2.68 g/L (12 hours after intervention), P = .003) and improved viscoelastic coagulation parameters (FIBTEM MCF, 27 vs 23 mm, P = .022). CONCLUSION: This randomized, controlled trial demonstrates that point-of-care guided and prophylactic treatment with fibrinogen concentrate does not reduce transfusion of blood products in a setting of unexpectedly low transfusion rate as tested in this cohort, but may improve coagulation parameters in the setting of high-risk cardiac surgery.

Clinical outcomes of mitral valve intervention in patients with mitral annular calcification: A systematic review and meta-analysis.

BACKGROUND: Mitral valve (MV) disease with mitral annular calcification (MAC) poses a surgical challenge and the clinical outcomes of MV surgery as well as transcatheter mitral valve replacement (TMVR) remain relatively unexplored. We performed a systematic review and meta-analysis to assess the effects of MAC on clinical outcomes following MV surgery and TMVR. METHODS: We searched MEDLINE and EMBASE databases until February 2019 for studies comparing clinical outcomes of MV surgery or TMVR in patients with and without MAC. Data were extracted by two independent investigators. Outcomes were perioperative and midterm complications and mortality. RESULTS: Seven observational studies enrolling 2902 patients were included. MAC patients were older, more likely to be female with greater chronic lung disease and kidney failure. Perioperative mortality was similar between patients with and without MAC undergoing MV surgery (risk ratio [RR], 1.15; 95% confidence interval [CI], 0.50-2.65; P = .74). MAC was associated with a higher risk of bleeding, permanent pacemaker implantation, and periprosthetic leak. Midterm mortality was greater in MAC patients undergoing MV surgery (incident rate ratio [IRR], 1.32; 95% CI, 1.05-1.67; P = .02). MAC patients undergoing TMVR had higher perioperative (RR, 4.65; 95% CI, 2.93-7.38; P < .01) and 1-year (RR, 5.44; 95% CI, 3.49-8.49; P < .01) mortality, decreased procedural success, greater left ventricular outflow tract obstruction and need for conversion to surgery when compared with patients undergoing TMVR for dysfunction of a bioprosthetic valve or annuloplasty ring. CONCLUSION: MV procedures in patients with MAC are associated with higher mortality and morbidity. This is largely driven by the high-risk patient profile associated with MAC. TMVR holds promise but has important limitations and should be reserved for select patients.

Variability in opioid prescribing practices among cardiac surgeons and trainees.

BACKGROUND AND AIM: The opioid epidemic has become a major public health crisis in recent years. Discharge opioid prescription following cardiac surgery has been associated with opioid use disorder; however, ideal practices remain unclear. Our aim was to examine current practices in discharge opioid prescription among cardiac surgeons and trainees. METHODS: A survey instrument with open- and closed-ended questions, developed through a 3-round Delphi method, was circulated to cardiac surgeons and trainees via the Canadian Society of Cardiac Surgeons. Survey questions focused on routine prescription practices including type, dosage and duration. Respondents were also asked about their perceptions of current education and guidelines surrounding opioid medication. RESULTS: Eighty-one percent of respondents reported prescribing opioids at discharge following routine sternotomy-based procedures, however, there remained significant variability in the type and dose of medication prescribed. The median (interquartile range) number of pills prescribed was 30 (20-30) with a median total dose of 135 (113-200) Morphine Milligram Equivalents. Informal teaching was the most commonly reported primary influence on prescribing habits and a lack of formal education regarding opioid prescription was associated with a higher number of pills prescribed. A majority of respondents (91%) felt that there would be value in establishing practice guidelines for opioid prescription following cardiac surgery. CONCLUSIONS: Significant variability exists with respect to routine opioid prescription at discharge following cardiac surgery. Education has come predominantly from informal sources and there is a desire for guidelines. Standardization in this area may have a role in combatting the opioid epidemic.

Impact on cardiac surgery volume of a comprehensive partnership with Integrated Health Solutions.

Background: The New Brunswick Heart Centre (NBHC) entered a contractual partnership with Integrated Health Solutions (IHS) to help address increasing wait times in the province of New Brunswick. Methods: Team leaders were identified from each of the target areas, including surgeons, anesthesiologists, nurses (operating room, intensive care unit [ICU] and postoperative ward), access coordinators and administrators. The methodology used was based on Lean principles and involved exercises by stakeholders aimed at identifying opportunities for improvement. A weekly dashboard was created to monitor and facilitate improvement efforts. No additional hospital beds or operating room theatres were added during the study period. Results: After 2 years, the annual number of cardiac surgical interventions increased from 788 to 873, representing a 10.8% increase in capacity. The best median wait time for patients decreased from 52 to 35 days (35% reduction). The best 90th percentile wait time decreased from 126 to 98 days (22% reduction). The overall increase in capacity could be explained in part by the significant increase in fast tracking from the ICU to the ward (> 2-fold) or bypassing the ICU altogether (4-fold increase reaching 13%). Despite these successes, challenges persist as the number of OR cancellations remained around 7.5% of all cases, mainly because of limited ICU resources. Conclusion: The NBHC-IHS partnership on this project has resulted in excellent engagement by stakeholders and promoted team cohesiveness. Furthermore, it has allowed significant reorganization and realignment of efforts to limit wait times and maximize overall capacity.

Contexte: Le New-Brunswick Heart Centre (NBHC) a conclu une entente contractuelle avec Integrated Health Solutions (IHS) pour remédier aux temps d'attente de plus en plus longs au Nouveau-Brunswick. Méthodes: Des chefs d'équipe ont été identifiés pour chaque domaine cible, notamment la chirurgie, l'anesthésie, les soins infirmiers (en salle d'opération, aux soins intensifs et en soins postopératoires), la coordination des soins et la direction. La méthodologie utilisée se fondait sur l'approche Lean et comprenait des exercices visant à relever les possibilités d'amélioration. Un tableau de bord hebdomadaire a été créé pour suivre et faciliter les mesures d'amélioration. On n'a ajouté aucun lit d'hôpital et aucune salle d'opération pendant la période étudiée. Résultats: Après 2 ans, le nombre de chirurgies cardiaques par année est passé de 788 à 873, une augmentation de 10,8 % de la capacité. Le temps d'attente médian pour les patients est tombé de 52 à 35 jours (réduction de 35 %). Le temps d'attente au 90e centile est passé de 126 à 98 jours (réduction de 22 %). L'augmentation générale de la capacité peut s'expliquer en partie par la réduction significative du temps passé aux soins intensifs avant l'admission en soins généraux (> 2 fois) ou par l'élimination complète du passage aux soins intensifs (augmentation de 400 %; 13 % des cas). Malgré ces réussites, des défis demeurent puisque le taux d'annulation des interventions est resté autour de 7,5 % des cas, surtout en raison des ressources limitées aux soins intensifs. Conclusion: Le partenariat NBHC­IHS sur ce projet a permis de mobiliser efficacement les participants et a favorisé la cohésion au sein de l'équipe. Il a en outre permis une importante réorganisation des ressources pour réduire les temps d'attente et augmenter la capacité générale.

Fibrosis independent atrial fibrillation in older patients is driven by substrate leukocyte infiltration: diagnostic and prognostic implications to patients undergoing cardiac surgery.

BACKGROUND: The objectives of the study were to characterize and quantify cellular inflammation and structural remodeling of human atria and correlate findings with molecular markers of inflammation and patient surrogate outcome. METHODS: Voluntary participants undergoing heart surgery were enrolled in the study and blood samples were collected prior to surgery, and right atrium samples were harvested intraoperatively. Blood samples were analyzed by flow cytometry and complete blood counts. Atrial samples were divided for fixed fibrosis analysis, homogenized for cytokine analysis and digested for single cell suspension flow cytometry. RESULTS: A total of 18 patients were enrolled and samples assessed. Isolated cells from the atria revealed a CD45+ population of ~ 20%, confirming a large number of leukocytes. Further characterization revealed this population as 57% lymphocytes and 26% monocyte/macrophages (MoΦ), with the majority of the latter cells being classical (CD14++/CD16-). Interstitial fibrosis was present in 87% of samples and correlated significantly with patient age. Older patients (> 65) had significantly more atrial fibrosis and cellular inflammation. AFib patients had no distinguishing feature of atrial fibrosis and had significantly greater CD45+ MoΦ, increased expression of MMP9 and presented with a significant correlation in length of stay to CCL-2/MCP-1 and NLR (neutrophil-to-lymphocyte ratio). CONCLUSION: Atrial fibrosis is correlated with age and not determinate to AFib. However, severity of atrial leukocyte infiltration and markers of matrix degradation are determinant to AFib. This also correlated with CCL2 (or MCP-1) and NLR-indicative of marked inflammation. These data show the potential importance of diagnostic and prognostic assessments that could inform clinical decision making in regard to the intensity of AFib patient management.

Regional differences in aortic valve replacements: Atlantic Canadian experience.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is evolving rapidly and is increasingly being adopted in the treatment of aortic valve disease. The goal of this study was to examine regional differences in surgical aortic valve replacement (SAVR) and TAVI across Atlantic Canada. METHODS: We identified all patients who underwent SAVR or TAVI between Jan. 1, 2010, and Dec. 31, 2014, in New Brunswick, Nova Scotia and Newfoundland and Labrador. Data obtained included patient demographic characteristics and surgical procedure details. We performed univariate descriptive analyses and calculated crude and age- and sex-adjusted incidence rates. RESULTS: A total of 3042 patients underwent SAVR or TAVI during the study period, 1491 in Nova Scotia, 1042 in New Brunswick and 509 in Newfoundland and Labrador. Patient demographic characteristics were similar across regions. A much higher proportion of patients in Newfoundland and Labrador (43.6%) than in Nova Scotia (4.2%) or New Brunswick (13.6%) received a mechanical versus a bioprosthetic valve. Rates of TAVI increased over the study period, with New Brunswick adopting their program before Nova Scotia (144 v. 74 procedures). Adjusted rates of all AVR procedures remained stable in Nova Scotia (40-50 per 100 000 people). Adjusted rates were lower in New Brunswick and Newfoundland and Labrador than in Nova Scotia; they increased slowly in New Brunswick over the study period. CONCLUSION: Despite geographical proximity and similar patient demographic characteristics, there existed regional differences in the management of aortic valve disease within Atlantic Canada. Further study is required to determine whether the observed differences in age- and sex-adjusted rates of AVR may be explained by geographical disease-related differences, varying practice patterns or barriers in access to care.

CONTEXTE: Le remplacement valvulaire aortique par cathéter, une méthode en pleine évolution, est de plus en plus utilisé pour le traitement des valvulopathies aortiques. Cette étude visait à examiner les différences régionales quant au remplacement valvulaire aortique par cathéter ou par chirurgie dans les provinces de l'Atlantique. MÉTHODES: Nous avons recensé tous les patients ayant subi un remplacement valvulaire aortique entre le 1er janvier 2010 et le 31 décembre 2014 au Nouveau-Brunswick, en Nouvelle-Écosse et à Terre-Neuve-et-Labrador. Nous avons recueilli des données sur les caractéristiques démographiques des patients et les interventions chirurgicales, puis nous avons réalisé une analyse descriptive univariée et avons calculé les taux d'incidence bruts et corrigés selon l'âge et le sexe. RÉSULTATS: En tout, 3042 patients ont subi un remplacement valvulaire aortique par cathéter ou par chirurgie pendant la période à l'étude : 1491 en Nouvelle-Écosse, 1042 au Nouveau-Brunswick et 509 à Terre-Neuve-et-Labrador. Les caractéristiques démographiques des patients étaient semblables d'une région à l'autre. La proportion des patients recevant une prothèse mécanique plutôt qu'une bioprothèse était beaucoup plus élevée à Terre-Neuve-et-Labrador (43,6 %) qu'en Nouvelle-Écosse (4,2 %) ou au Nouveau-Brunswick (13,6 %). Les taux de remplacement par cathéter ont augmenté au cours de la période à l'étude; le Nouveau-Brunswick a adopté un programme à ce sujet avant la Nouvelle-Écosse (144 c. 74 interventions). Les taux corrigés pour tous les remplacements étaient stables en Nouvelle-Écosse (40-50 par 100 000 habitants); ils étaient plus faibles au Nouveau-Brunswick et à Terre-Neuve-et-Labrador, mais ont augmenté lentement au Nouveau-Brunswick pendant la période à l'étude. CONCLUSION: Malgré la proximité géographique des provinces de l'Atlantique et les caractéristiques démographiques semblables des patients, il existait des différences dans la prise en charge des valvulopathies aortiques. D'autres études seront nécessaires pour déterminer si les variations dans les taux de remplacement corrigés selon l'âge et le sexe pourraient s'expliquer par des différences géographiques dans le nombre de cas, des différences dans les pratiques ou des obstacles à l'accès aux soins.

Glucolipotoxicity diminishes cardiomyocyte TFEB and inhibits lysosomal autophagy during obesity and diabetes.

Impaired cardiac metabolism in the obese and diabetic heart leads to glucolipotoxicity and ensuing cardiomyopathy. Glucolipotoxicity causes cardiomyocyte injury by increasing energy insufficiency, impairing proteasomal-mediated protein degradation and inducing apoptosis. Proteasome-evading proteins are degraded by autophagy in the lysosome, whose metabolism and function are regulated by master regulator transcription factor EB (TFEB). Limited studies have examined the impact of glucolipotoxicity on intra-lysosomal signaling proteins and their regulators. By utilizing a mouse model of diet-induced obesity, type-1 diabetes (Akita) and ex-vivo model of glucolipotoxicity (H9C2 cells and NRCM, neonatal rat cardiomyocyte), we examined whether glucolipotoxicity negatively targets TFEB and lysosomal proteins to dysregulate autophagy and cause cardiac injury. Despite differential effects of obesity and diabetes on LC3B-II, expression of proteins facilitating autophagosomal clearance such as TFEB, LAMP-2A, Hsc70 and Hsp90 were decreased in the obese and diabetic heart. In-vivo data was recapitulated in H9C2 and NRCM cells, which exhibited impaired autophagic flux and reduced TFEB content when exposed to a glucolipotoxic milieu. Notably, overloading myocytes with a saturated fatty acid (palmitate) but not an unsaturated fatty acid (oleate) depleted cellular TFEB and suppressed autophagy, suggesting a fatty acid specific regulation of TFEB and autophagy in the cardiomyocyte. The effect of glucolipotoxicity to reduce TFEB content was also confirmed in heart tissue from patients with Class-I obesity. Therefore, during glucolipotoxicity, suppression of lysosomal autophagy was associated with reduced lysosomal content, decreased cathepsin-B activity and diminished cellular TFEB content likely rendering myocytes susceptible to cardiac injury.

Nonclassical resident macrophages are important determinants in the development of myocardial fibrosis.

Macrophages are increasingly recognized as a potential therapeutic target in myocardial fibrosis via interactions with fibroblasts. We have characterized macrophage depletion and inhibition of nonclassical macrophage migration, in addition to direct interactions between nonclassical macrophages and fibroblasts in angiotensin II (AngII)-mediated, hypertensive myocardial fibrosis. Macrophage depletion was achieved by daily i.v. clodronate liposomes (-1 day to +3 days) during AngII infusion. Cx3cr1(-/-) mice were used to inhibit nonclassical macrophage migration. Macrophage phenotype (F4/80, CD11b, Ly6C) was characterized by immunofluorescence and flow cytometry. Collagen was assessed by Sirius Red/Fast Green. Quantitative real-time RT-PCR was performed for transcript levels. AngII/wild-type (WT) mice displayed significant infiltrate and fibrosis compared with saline/WT, which was virtually ablated by clodronate liposomes independent of hypertension. In vitro data supported M2 macrophages promoting fibroblast differentiation and collagen production. AngII/Cx3cr1(-/-) mice, however, significantly increased macrophage infiltrate and fibrosis relative to AngII/WT. AngII/Cx3cr1(-/-) mice also showed an M1 phenotypic shift relative to WT mice in, which the predominant phenotype was Ly6C(low), CD206(+) (M2). Myocardial IL-1ß was significantly up-regulated, whereas transforming growth factor ß down-regulated with this M1 shift. We demonstrated that infiltrating macrophages are critical to AngII-mediated myocardial fibrosis by preventing the development of fibrosis after liposomal depletion of circulating monocytes. Our findings also suggest that some macrophages, namely M2, may confer a protective myocardial environment that may prevent excessive tissue injury.

Disruption of collagen homeostasis can reverse established age-related myocardial fibrosis.

Heart failure, the leading cause of hospitalization of elderly patients, is correlated with myocardial fibrosis (ie, deposition of excess extracellular matrix proteins such as collagen). A key regulator of collagen homeostasis is lysyl oxidase (LOX), an enzyme responsible for cross-linking collagen fibers. Our objective was to ameliorate age-related myocardial fibrosis by disrupting collagen cross-linking through inhibition of LOX. The nonreversible LOX inhibitor ß-aminopropionitrile (BAPN) was administered by osmotic minipump to 38-week-old C57BL/6J male mice for 2 weeks. Sirius Red staining of myocardial cross sections revealed a reduction in fibrosis, compared with age-matched controls (5.84 ± 0.30% versus 10.17 ± 1.34%) (P < 0.05), to a level similar to that of young mice at 8 weeks (4.9 ± 1.2%). BAPN significantly reduced COL1A1 mRNA, compared with age-matched mice (3.5 ± 0.3-fold versus 15.2 ± 4.9-fold) (P < 0.05), suggesting that LOX is involved in regulation of collagen synthesis. In accord, fibrotic factor mRNA expression was reduced after BAPN. There was also a novel increase in Ly6C expression by resident macrophages. By interrupting collagen cross-linking by LOX, the BAPN treatment reduced myocardial fibrosis. A novel observation is that BAPN treatment modulated the transforming growth factor-ß pathway, collagen synthesis, and the resident macrophage population. This is especially valuable in terms of potential therapeutic targeting of collagen regulation and thereby age-related myocardial fibrosis.

Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial.

BACKGROUND: Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. METHODS: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase-myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. RESULTS: We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] -0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI -0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). INTERPRETATION: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01071265.

Endocarditis is not an Independent Predictor of Blood Transfusion in Aortic Valve Replacement Patients With Severe Aortic Regurgitation.

OBJECTIVE: This study sought to evaluate if the presence of endocarditis was independently associated with increased perioperative blood transfusion in patients undergoing aortic valve replacements (AVR) with aortic regurgitation. DESIGN: This was a retrospective study. SETTING: Large Canadian tertiary care hospital. PARTICIPANTS: Six hundred sixty-two consecutive patients with aortic regurgitation score of 3 or higher undergoing AVR from 1995 to 2012. INTERVENTIONS: No interventions were performed in this retrospective study. MEASUREMENTS AND MAIN RESULTS: After REB approval, data were obtained from a center-specific database. Univariate analysis was performed to identify variables that may be associated with transfusion of any allogeneic blood product perioperatively. A multivariate logistic regression was generated to identify independent predictors of perioperative transfusion. Unadjusted transfusion rates in patients with no endocarditis and with endocarditis were 32% and 70% (p<0.001), respectively. Independent predictors of any transfusion were moderate-to-severe preoperative anemia, preoperative renal failure, non-isolated AVR, age>70, urgent/emergent surgery, BMI<25, and female sex. Endocarditis was not an independent predictor of transfusion (OR = 0.748; 95% CI = 0.35-1.601). CONCLUSIONS: In patients undergoing AVR, unadjusted perioperative transfusion rates were higher when endocarditis was present. However, after adjustment, aortic valve endocarditis was not independently associated with blood transfusion. The authors' observation could be explained by the higher prevalence of many independent predictors of transfusion, such as comorbidities or more complex surgery, within the endocarditis group. Thus, AV endocarditis, in the absence of other risk factors, was not associated with increased perioperative transfusion risk.

Creation of the sole regional laser lead extraction program serving Atlantic Canada: initial experience.

BACKGROUND: An increasing need for laser lead extraction has grown in parallel with the increase of implantation of pacing and defibrillating devices. We reviewed the initial experience of a regional laser-assisted lead extraction program serving Atlantic Canada. METHODS: We retrospectively reviewed the cases of all consecutive patients who underwent laser lead extraction at the Maritime Heart Centre in Halifax, NS, between 2006 and 2015. We conducted univariate and Kaplan-Meier survivorship analyses. RESULTS: During the 9-year study period, 108 consecutive patients underwent laser lead extractions (218 leads extracted). The most common indication for extraction was infection (84.3%). Most patients were older than 60 years (73.1%) and had leads chronically implanted; the explanted leads were an average of 7.5 ± 6.8 years old. Procedural and clinical success (resolution of preoperative symptoms) rates and mortality were 96.8%, 97.2%, and 0.9%, respectively. Sternotomy procedures were performed in 3 instances: once for vascular repair due to perforation and twice to ensure that all infected lead material was removed. No minor complications required surgical intervention. Survival after discharge was 98.4% at 30 days and 94% at 12 months. CONCLUSION: Atlantic Canada's sole surgical extraction centre achieved high extraction success with a low complication rate. Lead extraction in an operative setting provides for immediate surgical intervention and is essential for the survival of patients with complicated cases. Surgeons must weigh the risks versus benefits in patients older than 60 years who have chronically implanted leads (> 1 yr) and infection.

CONTEXTE: La demande en matière d'extraction de sondes par laser a augmenté parallèlement à l'installation de stimulateurs et de défibrillateurs cardiaques. Nous nous sommes penchés sur les débuts d'un programme d'extraction de sondes par laser dans les provinces de l'Atlantique. MÉTHODES: Nous avons étudié rétrospectivement les dossiers de tous les patients consécutifs ayant subi une extraction de sondes par laser au Maritime Heart Centre à Halifax (N.-É), entre 2006 et 2015. Nous avons mené une analyse unidimensionnelle et une analyse de survie selon la méthode de Kaplan-Meier. RÉSULTATS: Pendant les 9 années à l'étude, 108 patients consécutifs ont subi une extraction de sondes par laser (218 sondes retirées). La cause d'extraction la plus fréquente était l'infection (84,3 %). La plupart des patients étaient âgés de plus de 60 ans (73,1 %), et leurs sondes avaient été installées de façon permanente. Les sondes extraites avaient été installées en moyenne 7,5 ± 6,8 ans plus tôt. Le taux de réussite de l'intervention, le taux de réussite clinique (soulagement des symptômes préopératoires) et le taux de mortalité se chiffraient respectivement à 96,8 %, à 97,2 % et à 0,9 %. Trois sternotomies ont dû être effectuées, dans 1 cas pour réparer les parois vasculaires à la suite d'une perforation, et dans les 2 autres cas pour s'assurer du retrait de tous les éléments infectés de la sonde. Aucune complication mineure n'a nécessité d'intervention chirurgicale. Le taux de survie après 30 jours et 12 mois suivant le congé des patients étaient de 98,4 % et de 94 %, respectivement. CONCLUSION: Le seul centre d'extraction de sondes dans les provinces de l'Atlantique obtient un taux élevé de réussite et un faible taux de complications. L'extraction de sondes en milieu opératoire permet de pratiquer immédiatement des interventions chirurgicales et est essentielle à la survie des patients dont les cas sont complexes. Les chirurgiens doivent évaluer les risques et les avantages pour les patients de plus de 60 ans qui montrent des signes d'infection et chez qui les sondes ont été installées depuis un certain temps (> 1 an).

Methylprednisolone Does Not Reduce Persistent Pain after Cardiac Surgery.

BACKGROUND: Persistent incisional pain is common after cardiac surgery and is believed to be in part related to inflammation and poorly controlled acute pain. Methylprednisolone is a corticosteroid with substantial antiinflammatory and analgesic properties and is thus likely to ameliorate persistent surgical pain. Therefore, the authors tested the primary hypothesis that patients randomized to methylprednisolone have less persistent incisional pain than those given placebo. METHODS: One thousand forty-three patients having cardiopulmonary bypass for cardiac surgery via a median sternotomy were included in this substudy of Steroids in Cardiac Surgery (SIRS) trial. Patients were randomized to 500 mg intraoperative methylprednisolone or placebo. Incisional pain was assessed at 30 days and 6 months after surgery, and the potential risk factors were also evaluated. RESULTS: Methylprednisolone administration did not reduce pain at 30 days or persistent incisional pain at 6 months, which occurred in 78 of 520 patients (15.7%) in the methylprednisolone group and in 88 of 523 patients (17.8%) in the placebo group. The odds ratio for methylprednisolone was 0.93 (95% CI, 0.79 to 1.09, P = 0.37). Furthermore, there was no difference in worst pain and average pain in the last 24 h, pain interference with daily life, or use of pain medicine at 6 months. Younger age, female sex, and surgical infections were associated with the development of persistent incisional pain. CONCLUSIONS: Intraoperative methylprednisolone administration does not reduce persistent incisional pain at 6 months in patients recovering from cardiac surgery.

Does more than a single chest tube for mediastinal drainage affect outcomes after cardiac surgery?

BACKGROUND: The use of 1 or more mediastinal chest tubes has traditionally been routine for all cardiac surgery procedures to deal with bleeding. However, it remains unproven whether multiple chest tubes offer a benefit over a single chest tube. METHODS: All consecutive patients undergoing cardiac surgery (2005-2010) received at least 1 chest tube at the time of surgery based on surgeon preference. Patients were grouped into those receiving a single chest tube (SCT) and those receiving multiple chest tubes (MCT). The primary outcome was return to the operating room for bleeding or tamponade. RESULTS: A total of 5698 consecutive patients were assigned to 2 groups: 3045 to the SCT and 2653 to the MCT group. Patients in the SCT group were older, more often female and less likely to undergo isolated coronary artery bypass graft than those in the MCT group. Unadjusted outcomes for SCT and MCT, respectively, were return to the operating room for bleeding or tamponade (4.7% v. 5.0%; p = 0.50), intensive care unit stay longer than 48 hours (25.5% v. 27.9%; p = 0.041, postoperative stay > 9 days (31.5% v. 33.1%; p = 0.20) and mortality (3.8% v. 4.6%; p = 0.16). Logistic regression analysis, adjusted for clinical differences between groups, showed that the number of chest tubes was not associated with return to the operating room for bleeding or tamponade. CONCLUSION: The use of multiple mediastinal chest tubes after cardiac surgery confers no advantage over a single chest tube in preventing return to the operating room for bleeding or tamponade.

Regulation and role of connective tissue growth factor in AngII-induced myocardial fibrosis.

Exposure of rodents to angiotensin II (AngII) is a common model of fibrosis. We have previously shown that cellular infiltration of bone marrow-derived progenitor cells (fibrocytes) occurs before deposition of extracellular matrix and is associated with the production of connective tissue growth factor (CTGF). In the present study, we characterized the role of CTGF in promoting fibrocyte accumulation and regulation after AngII exposure. In animals exposed to AngII using osmotic minipumps (2.0 µg/kg per min), myocardial CTGF mRNA peaked at 6 hours (21-fold; P < 0.01), whereas transforming growth factor-ß (TGF-ß) peaked at 3 days (fivefold; P < 0.05) compared with saline control. Early CTGF expression occurred before fibrocyte migration (1 day) into the myocardium or ECM deposition (3 days). CTGF protein expression was evident by day 3 of AngII exposure and seemed to be localized to resident cells. Isolated cardiomyocytes and microvascular endothelial cells responded to AngII with increased CTGF production (2.1-fold and 2.8-fold, respectively; P < 0.05), which was abolished with the addition of anti-TGF-ß neutralizing antibody. The effect of CTGF on isolated fibrocytes suggested a role in fibrocyte proliferation (twofold; P < 0.05) and collagen production (2.3-fold; P < 0.05). In summary, we provide strong evidence that AngII exposure first resulted in Smad2-dependent production of CTGF by resident cells (6 hours), well before the accumulation of fibrocytes or TGF-ß mRNA up-regulation. In addition, CTGF contributes to fibrocyte proliferation in the myocardium and enhances fibrocyte differentiation into a myofibroblast phenotype responsible for ECM deposition.

Early fibroblast progenitor cell migration to the AngII-exposed myocardium is not CXCL12 or CCL2 dependent as previously thought.

Fibroblast progenitor cells (fibrocytes) are important to the development of myocardial fibrosis and are suggested to migrate to the heart via CXCL12 and chemokine ligand (CCL) 2. We hypothesized that if these chemokines are recruiting fibrocytes, disrupting their signaling will reduce early (3-day) fibrocyte infiltration and, consequently, fibrosis in the myocardium. C57/Bl6 and CCR2(-/-) mice were infused with saline or angiotensin (Ang) II, with or without CXC receptor 4 blockade (AMD3100). Hearts were assessed for chemokine up-regulation, immunofluorescence, and histological features. AngII caused early myocardial up-regulation of CXCL12 and CCL2, which corresponded to significant myocardial infiltration and fibrosis compared with controls. Animals receiving AMD3100 and/or with the genotype CCR2(-/-) failed to demonstrate reductions in infiltrate or fibrosis after 3 days of AngII, and AngII + AMD3100 animals showed exacerbated fibrocyte infiltration and fibrosis compared with AngII alone. CCR2(-/-) mice demonstrated significant reductions in myocardial fibrosis relative to wild type, but this was after 28 days of AngII infusion and was the result of reduced infiltrating cell proliferation. An alternative CCR2 ligand, CCL12, was found to be increasing infiltrating cell proliferation in the heart after AngII infusion, which we confirmed in vitro. In conclusion, early fibrocyte recruitment cannot be inhibited through modulating CXCL12 or CCL2, as previously thought. Ablating CCR2 signaling did confer myocardial fibrosis reductions, but these benefits were not observed until much later and were likely the result of modulated proliferation through ablating the CCL12-CCR2 interaction.

Arrhythmogenic right ventricular cardiomyopathy: use of a left ventricular assist device as a bridge to transplantation?

The principal characteristic of arrhythmogenic right ventricular cardiomyopathy (ARVC) is the tendency for ventricular arrhythmia and sudden death to occur without overt ventricular dysfunction. Current recommendations for management of patients with ARVC include insertion of an automated implantable cardioverter-defibrillator (AICD) to prevent sudden cardiac death. However, despite the use of AICD and/or anti-arrhythmic drugs some patients suffer recurrent ventricular arrhythmias unresponsive to optimum medical management. We present two cases of ARVC with refractory recurrent ventricular arrhythmias that were successfully managed by left ventricular assist device (LVAD) implantation, as a bridge to transplant (BTT). These two cases are unconventional examples of use of LVAD, given the predominant right ventricular pathology of ARVC and the arrhythmogenic nature of their presentation. The novelty of these cases should be taken in the context of increasing pressure to standardize indications for use of mechanical circulatory support.