Utilization of Shock Team and Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) in the Management of Cardiogenic Shock in Northern Ontario.

Background: Despite advancements in critical care and coronary revascularization, cardiogenic shock (CS) outcomes remain poor. Implementing a shock team and use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) have been associated with improved CS outcomes, but its feasibility in remote and rural areas remains unknown. Methods: This retrospective study included patients with CS who required mechanical circulatory support (MCS) at Health Sciences North, Sudbury, Ontario. The analysis aimed to accomplish 2 objectives: first, to review the outcomes associated with use of Impella (Abiomed, Danvers, MA) and, second, to assess the feasibility of establishing a shock team to facilitate the local implementation of VA-ECMO. The primary endpoint was in-hospital mortality. Results: The outcomes of 15 patients with CS who received Impella between 2015 and 2021 were reviewed. Their average age was 65 years (standard deviation [SD]: 13), and 8 patients (53%) were female. CS was ischemic in 12 patients (80%). Transfemoral Impella CP (cardiac power) was the most frequently used (93%). Thirteen patients (87%) died during the index hospital stay post-Impella because of progressive circulatory failure. The shock team was established following consultations with several Canadian MCS centres, leading to the development of a protocol to guide use of MCS. There have been 4 cases in which percutaneous VA-ECMO using Cardiohelp (Getinge/Maquet, Wayne, NJ) has been used; 3 (75%) survived beyond the index hospitalization. Conclusions: This analysis demonstrated the feasibility of implementing a shock team in remote Northern Ontario, enabling the use of VA-ECMO with success in a centre with a sizeable rural catchment area. This initiative helps address the gap in cardiac care outcomes between rural and urban areas in Ontario.

Introduction: En dépit des avancées des soins aux patients en phase critique et de la revascularisation coronarienne, les résultats du choc cardiogénique (CC) semblent mauvais. La mise en place d'une équipe de choc et l'utilisation de l'oxygénation extracorporelle (ECMO, de l'anglais extracorporeal membrane oxygenation) par voie veino-artérielle (VA) (VA-ECMO) ont été associées à de meilleurs résultats du CC, mais on ignore sa faisabilité dans les régions éloignées et rurales. Méthodes: La présente étude rétrospective portait sur des patients en CC qui ont eu besoin d'une assistance circulatoire mécanique (ACM) à Horizon Santé-Nord, à Sudbury, en Ontario. L'analyse visait 2 objectifs : le premier objectif était de passer en revue les résultats associés à l'utilisation de Impella (Abiomed, Danvers, MA) et, le deuxième était d'évaluer la faisabilité de la mise en place d'une équipe de choc pour faciliter la mise en œuvre locale de la VA-ECMO. Le principal critère d'évaluation était la mortalité intrahospitalière. Résultats: Nous avons passé en revue les résultats cliniques de 15 patients ayant subi un CC qui avaient reçu une Impella entre 2015 et 2021. L'âge moyen était de 65 ans (écart type [ET] : 13), et 8 patients (53 %) étaient des femmes. Le CC était d'origine ischémique chez 12 patients (80 %). L'Impella CP (cardiac power, soit la pompe cardiaque) par voie transfémorale était la plus fréquemment utilisée (93 %). Treize patients (87 %) sont morts durant le séjour de référence à l'hôpital après l'utilisation de l'Impella en raison d'insuffisance circulatoire progressive. La mise en place de l'équipe de choc à la suite des consultations dans plusieurs centres canadiens d'ACM a mené à l'élaboration d'un protocole d'utilisation de l'ACM. Il y a eu 4 cas chez lesquels la VA-ECMO par voie percutanée à l'aide de Cardiohelp (Getinge/Maquet, Wayne, New Jersey, É.-U.) a été utilisée ; 3 (75 %) ont survécu après l'hospitalisation de référence. Conclusions: Cette analyse a démontré la faisabilité de la mise en place d'une équipe de choc dans les régions éloignées du nord de l'Ontario, qui a permis d'utiliser efficacement la VA-ECMO dans un centre d'une circonscription hospitalière rurale non négligeable. Cette initiative aide à remédier à l'écart des résultats en soins cardiaques entre les régions rurales et urbaines de l'Ontario.

Intermediate-term Outcomes Following a Case Series of Reoperations for Medtronic Freestyle Stentless Aortic Valves.

Background: Data are limited on long-term outcomes in patients who have undergone a reoperation following failure of a stentless aortic valve. Methods: Between 2006 and 2016, a retrospective analysis was performed on 24 patients who underwent open aortic valve replacement surgery for a failed stentless aortic valve prosthesis at Health Sciences North, Sudbury, Ontario, Canada. The primary outcome was a low mortality rate from cardiac-related deaths after 5 years. Results: All patients underwent insertion of a Medtronic Freestyle bioprosthesis (Minneapolis, MN) implanted using the modified subcoronary technique for their initial operation. The interval from the first operation to the stentless redo surgery ranged from 6 to 13 years. Aortic valve reoperation was performed for structural valve deterioration in 96% (n = 23) of the cases. Reoperations involved a removal of the stented valve leaflets and standard aortic valve replacement within the stentless casing in 20% (n = 5) of the cases, with the remaining cases requiring complete removal of the stentless prosthesis and aortic valve replacement. In those in whom a complete removal of the stentless valve was possible (n = 19), no disruption of the native aortic root occurred, with a 0% rate of conversion to a Bentall procedure. No intraoperative mortality occurred. The 30-day and 10-year operative mortality rates were 4% and 16%, respectively. Conclusions: Redo surgery for failing stentless valves can be done with relatively low risk and with acceptable long-term outcomes without resorting to root-replacement techniques.

Contexte: Il existe peu de données sur les résultats à long terme chez les patients qui ont subi une réintervention chirurgicale après une défaillance d'une valve aortique sans armature (stentless) ayant été implantée. Méthodologie: Nous avons réalisé une analyse rétrospective, de 2006 à 2016, auprès de 24 patients ayant subi une intervention chirurgicale invasive de remplacement de valve aortique en raison de la défaillance d'une prothèse aortique sans armature à l'hôpital Health Sciences North situé à Sudbury (Ontario), au Canada. Le paramètre principal d'évaluation était un faible taux de mortalité d'origine cardiaque après 5 ans. Résultats: Tous les patients avaient initialement subi l'implantation d'une bioprothèse Medtronic Freestyle (Minneapolis, Minnesota) par la technique sous-coronaire modifiée. La période écoulée entre la première intervention chirurgicale et la réintervention au niveau de la valve sans armature allait de 6 à 13 ans. Dans 96 % des cas (n = 23), la réintervention était réalisée en raison d'une détérioration de structure de la valve aortique. La réintervention avait consisté en un retrait des cuspides avec armature et un remplacement de valve aortique standard dans la membrane sans armature dans 20 % des cas (n = 5) et un retrait complet de la prothèse sans armature avec remplacement de la valve aortique avait été nécessaire dans les autres cas. Chez les patients pour qui le retrait complet de la valve sans armature a été possible (n = 19), aucune déchirure de la racine aortique native n'est survenue et le taux de passage à une intervention de Bentall était de 0 %. Aucun décès peropératoire n'est survenu. Les taux de mortalité à 30 jours et à 10 ans s'élevaient à 4 % et à 16 %, respectivement. Conclusions: La réintervention chirurgicale après la défaillance d'une valve aortique sans armature peut être réalisée avec des risques re-lativement faibles et des résultats à long terme acceptables sans avoir recours à des techniques de remplacement de la racine aortique.

The Safety of Early Discharge Following Transcatheter Aortic Valve Implantation Among Patients in Northern Ontario and Rural Areas Utilizing the Vancouver 3M TAVI Study Clinical Pathway.

Background: Early hospital ( < 48 hours) discharge following transcatheter aortic valve implantation (TAVI) is an increasingly adopted practice; however, data on the safety of such an approach among patients residing in North Ontario, including remote and medically underserved areas, are lacking. Methods: This retrospective study included patients who underwent TAVI in Sudbury, Ontario. The safety of early discharge after implementation of the Vancouver 3M (multidisciplinary, multimodality, but minimalist) clinical pathway was assessed. The primary endpoint was 30-day mortality. Resource utilization before vs after 3M clinical pathway implementation was also compared. Results: A total of 291 patients who underwent TAVI between 2012 and 2021 were included in the study. One in-hospital death (0.6%) occurred after the 3M clinical pathway implementation, with no mortality observed beyond hospital discharge. Eleven patients (6.7%) required rehospitalization within 30 days. The need for mechanical ventilation and surgical vascular cut-down declined from 100% and 97%, respectively, at baseline, to 6% and 2%. The number of patients receiving TAVI on a given procedural day increased from 2 to 3 patients. The median post-TAVI hospital length of stay decreased from 5 days (2-6 days) to 1 day (1-3 days) after 3M clinical pathway implementation. Conclusions: Following TAVI, early discharge of selected patients residing in Northern Ontario, including rural areas, using the Vancouver 3M clinical pathway was associated with favourable outcomes, short length of stay, and more-efficient resource utilization. These data can help improve healthcare efficiency and bridge variations in TAVI funding and accessibility in underserved locations.

Contexte: Il est de plus en plus admis d'accorder un congé rapide de l'hôpital (< 48 heures) après une implantation valvulaire aortique par cathéter (IVAC); toutefois, on ne dispose pas de données sur l'innocuité de cette pratique pour les patients du nord de l'Ontario, y compris ceux qui résident en régions éloignées moins bien desservies par les services médicaux. Méthodologie: Cette étude rétrospective a porté sur des patients ayant subi une IVAC à Sudbury (Ontario). L'innocuité d'un congé rapide après l'implantation selon le parcours de soins Vancouver 3M (multidisciplinaire, multimodal, mais minimaliste) a été évaluée. Le principal paramètre d'évaluation était la mortalité à 30 jours. Une comparaison de l'utilisation des ressources avant et après la mise en œuvre du parcours de soins 3M a également été effectuée. Résultats: Au total, 291 patients ayant subi une IVAC entre 2012 et 2021 ont été inclus dans l'étude. Un décès à l'hôpital (0,6 %) est survenu après la mise en œuvre du parcours de soins 3M, et aucune mortalité n'a été relevée après le congé de l'hôpital. Onze patients (6,7 %) ont dû être réhospitalisés dans les 30 jours suivants. Le recours à la ventilation mécanique et à la dénudation vasculaire a chuté, passant de 100 % et 97 % au départ, respectivement, à 6 % et 2 %. Le nombre de patients par jour d'intervention subissant une IVAC est passé de deux à trois patients. À la suite de la mise en œuvre du parcours de soins 3M, la durée médiane du séjour à l'hôpital après une IVAC est passée de cinq jours (deux à six jours) à un jour (un à trois jours). Conclusions: Après une IVAC, le congé rapide de patients sélectionnés habitant dans le nord de l'Ontario, y compris ceux habitant en région rurale, selon le parcours de soins Vancouver 3M a été associé à des résultats de santé favorables, à une durée courte d'hospitalisation et à une utilisation plus efficace des ressources. Ces données peuvent contribuer à améliorer l'efficacité des soins de santé et à combler des écarts liés aux variations du financement et de l'accessibilité des IVAC dans les régions moins bien desservies.

Erroneous Pressure Reading from an Unpowered Intra-aortic Balloon Pump: Case Report.

Intra-aortic balloon pump (IABP) technology is an established treatment modality for patients with acute cardiac failure. Advances in IABP technology have simplified use and reliability such that electromechanical malfunctions are relatively rare. We present a case of an unanticipated pressure output signal from a powered off Cardiosave IABP console resulting in an erroneous mean arterial blood pressure waveform being displayed during cardiopulmonary bypass. The patient suffered no ill effects and made a full recovery. As a result of this incident, our policies have been revised to ensure that all patients with an IABP brought to the operating room for surgery have at least two arterial lines, one of which is not off the IABP, to prevent future occurrences.

Risk score for arch reconstruction under circulatory arrest with hypothermia: The ARCH score.

OBJECTIVE: Currently, there is no risk scores built to predict risk in thoracic aortic surgery. This study aims to develop and internally validate a risk prediction score for patients who require arch reconstruction with hypothermic circulatory arrest. METHODS: From 2002 to 2018, data for 2270 patients who underwent aortic arch surgery in 12 institutions in Canada were retrospectively collected. The outcomes modeled included in-hospital mortality and a modified Society of Thoracic Surgeons-defined composite for mortality or major morbidity. Multivariable logistic regression using least absolute shrinkage and selection operator selection method and mixed-effect regression model was used to select the predictors. Internal calibration of the final models is presented with an observed-versus-predicted plot. RESULTS: There were 182 in-hospital deaths (8.0%), and the incidence of Society of Thoracic Surgeons-defined composite for mortality or major morbidity was 27.9%. Variables that increased risk of mortality are age, chronic obstructive pulmonary disease, atrial fibrillation, peripheral vascular disease, New York Heart Association class ≥III symptoms, acute aortic dissection or rupture, use of elephant trunk, concomitant surgery, and increased cardiopulmonary bypass time, with median c-statistics of 0.85 on internal validation. The c-statistics was 0.77 for the model predicting Society of Thoracic Surgeons-defined composite. Internal assessment shows good overall calibration for both models. CONCLUSIONS: We developed and internally validated a risk score for patients undergoing arch surgery requiring hypothermic circulatory arrest using a multicenter database. Once externally validated, the ARCH (Arch Reconstruction under Circulatory arrest with Hypothermia) score would allow for better patient risk-stratification and aid in the decision-making process for surgeons and patient prior to surgery.

Evolving Surgical Techniques and Improving Outcomes for Aortic Arch Surgery in Canada.

BACKGROUND: To explore evolving surgical techniques and outcomes for aortic arch surgery. METHODS: A total of 2435 consecutive patients underwent aortic arch repair with hypothermic circulatory arrest between 2008 and 2018 in 12 institutions across Canada. Trends in patient characteristics, surgical techniques, and in-hospital outcomes, including major morbidity or mortality, were examined. RESULTS: From 2008 to 2018, the age of patients (62.3 ± 13.2 years) and the proportion of women (30.2%) undergoing arch surgery did not change significantly. Aortic diameters at operation decreased (2008: 58 ± 13 mm; 2018: 53 ± 11 mm; P < 0.01). Surgeons performed more valve-sparing root replacements (2008: 0%; 2018: 15%; P < 0.001) and fewer Bentall procedures (2008: 27%; 2018: 20%; P < 0.01). Total arch replacement rates were similar (P = 0.18); however, elephant trunk (2008: 9.5%; 2018: 19%; P < 0.001) and frozen elephant trunk (2008: 3.1%; 2018: 15%; P < 0.001) repair rates have increased. Over time, higher nadir temperatures (2008: 18 [17-21]°C; 2018: 25 [23-28]°C; P < 0.001), and more frequent antegrade cerebral perfusion (2008: 61%; 2018: 83%; P < 0.001) were used. For elective cases, in-hospital mortality rates declined (2008: 6.8%; 2018: 1.2%; P = < 0.01), as did major morbidity or mortality (2008: 24%; 2018: 13%; P < 0.001) and transfusion rates (2008: 61%; 2018: 41%; P < 0.001), but stroke rates remained constant (2008: 6.8%; 2018: 5.3%; P = 0.12). Outcomes remained the same over time for urgent or emergent cases. CONCLUSIONS: Outcomes have improved over the past decade in Canada for elective aortic arch surgery, in the context of operating on smaller aortas, and more frequent use of moderate hypothermia and antegrade cerebral perfusion. Further research is needed to improve stroke rates and outcomes in the emergency setting.

INTRODUCTION: Examiner l'évolution des techniques chirurgicales et les résultats de l'intervention chirurgicale de l'arc aortique. MÉTHODES: Un total de 2 435 patients consécutifs ont subi une réparation de l'arc aortique en arrêt circulatoire en hypothermie entre 2008 et 2018 dans 12 établissements du Canada. Nous avons examiné les tendances en ce qui concerne les caractéristiques des patients, les techniques chirurgicales et les résultats cliniques intrahospitaliers, y compris les principales causes de morbidité ou de mortalité. RÉSULTATS: De 2008 à 2018, l'âge des patients (62,3 ± 13,2 ans) et la proportion de femmes (30,2 %) subissant l'intervention chirurgicale de l'arc n'a pas montré de changement significatif. Les diamètres aortiques à l'opération ont diminué (2008 : 58 ± 13 mm; 2018 : 53 ± 11 mm; P < 0,01). Les chirurgiens ont réalisé un plus grand nombre de remplacements de la racine aortique sans remplacement de la valve (2008 : 0 %; 2018 : 15 %; P < 0,001) et un moins grand nombre d'opérations de Bentall (2008 : 27 %; 2018 : 20 %; P < 0,01). Les taux totaux de remplacements de l'arc étaient similaires (P = 0,18). Toutefois, les taux de réparation avec la technique de la trompe d'éléphant; (2008 : 9,5 %; 2018 : 19 %; P < 0,001) et de la trompe d'éléphant congelée (2008 : 3,1 %; 2018 : 15 %; P < 0,001) ont augmenté. Avec le temps, des nadirs supérieurs de température (2008 : 18 [17-21]°C; 2018 : 25 [23-28]°C; P < 0,001) et des perfusions cérébrales antérogrades plus fréquentes (2008 : 61 %; 2018 : 83 %; P < 0,001) ont été utilisés. Pour les cas non urgents, les taux de mortalité intrahospitalière (2008 : 6,8 %; 2018 : 1,2 %; P = < 0,01) et les taux de morbidité grave et de mortalité (2008 : 24 %; 2018 : 13 %; P < 0,001) et de transfusion (2008 : 61 %; 2018 : 41 %; P < 0,001) ont décru, mais les taux d'accidents vasculaires cérébraux (2008 : 6,8 %; 2018 : 5,3 %; P = 0,12) sont demeurés constants. Les résultats cliniques sont demeurés identiques au fil du temps pour les cas urgents ou les nouveaux cas. CONCLUSIONS: Au Canada, les résultats de l'intervention chirurgicale non urgente de l'arc aortique se sont améliorés au cours de la dernière décennie dans le contexte de l'opération d'aortes plus petites et de l'utilisation plus fréquente de l'hypothermie modérée et de la perfusion cérébrale antérograde. D'autres recherches sont nécessaires pour améliorer les taux d'accidents vasculaires cérébraux et les résultats cliniques dans le cadre d'interventions urgentes.

The impact of age on patients undergoing aortic arch surgery: Evidence from a multicenter national registry.

OBJECTIVE: Elderly patients are typically offered aortic surgery at similar diameter thresholds as younger patients, despite limited data quantifying their operative risk. We aim to report the incremental risk experienced by elderly patients undergoing aortic arch surgery. METHODS: In total, 2520 patients underwent aortic arch surgery between 2002 and 2018 in 10 centers. Patients were divided into 3 groups: <65 years (n = 1325), 65 to 74 years (n = 737), and ≥75 years (n = 458). Outcomes of interest were in-hospital mortality, stroke, and the modified Society of Thoracic Surgeons composite for mortality or major morbidity (STS-COMP). Multivariable modeling was performed to determine the association of age with these outcomes. RESULTS: As age increased, there was an increasing rate of comorbidities, including diabetes (P < .001), renal failure (P < .001), and previous stroke (P = .01). Rates of acute aortic syndrome (P = .50) and total arch repair were similar (P = .59) between groups. Older patients had greater mortality (<65: 6.1% vs 65-74: 9.0% vs ≥75: 14%, P < .001), stroke (6.3% vs 7.7% vs 11%, P = .01) and STS-COMP (25% vs 32% vs 38%, P < .001). After multivariable risk-adjustment, a step-wise increase in complications was observed in the older age groups relative to the youngest in terms of in-hospital mortality (65-74: odds ratio [OR] 1.57, P = .04; ≥75: OR, 2.94, P = .001) and STS-COMP (65-74: OR, 1.57, P < .001; ≥75: OR, 1.96, P < .001). CONCLUSIONS: Older patients experienced elevated rates of mortality and morbidity following aortic arch surgery. These results support a more measured approach when evaluating elderly patients. Further research is needed on age-dependent natural history of thoracic aneurysms and size thresholds for intervention.

Impact of brain protection strategies on mortality and stroke in patients undergoing aortic arch repair with hypothermic circulatory arrest: evidence from the Canadian Thoracic Aortic Collaborative.

OBJECTIVES: The aim of this study was to investigate the impact of various brain perfusion techniques and nadir temperature cooling strategies on outcomes after aortic arch repair in a contemporary, multicentre cohort. METHODS: A total of 2520 patients underwent aortic arch repair with hypothermic circulatory arrest (HCA) between 2002 and 2018 in 11 centres of the Canadian Thoracic Aortic Collaborative. Primary outcomes included mortality; stroke; a composite of mortality or stroke; and a Society of Thoracic Surgeons-defined composite (STS-COMP) end point for mortality or major morbidity including stroke, reoperation, renal failure, prolonged ventilation and deep sternal wound infection. Multivariable logistic regression and propensity score matching were performed for cerebral perfusion and nadir temperature practices. RESULTS: Antegrade cerebral perfusion was found on multivariable analysis to be protective against mortality [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.48-0.86; P = 0.005], stroke (OR 0.55, 95% CI 0.37-0.81; P = 0.006), composite of mortality or stroke (OR 0.57, 95% CI 0.45-0.72; P = 0.0001) and STS-COMP (OR 0.53, 95% CI 0.41-0.67; P < 0.0001), as compared to HCA alone. Retrograde cerebral perfusion yielded similar outcomes as compared to antegrade cerebral perfusion. When compared to HCA with nadir temperature <24°C, a propensity score analysis of 647 matched pairs identified nadir temperature ≥24°C as predictor of lower mortality (OR 0.62, 95% CI 0.40-0.98; P = 0.04), stroke (OR 0.51, 95% CI 0.31-0.84; P = 0.008), composite of mortality or stroke (OR 0.62, 95% CI 0.43-0.89; P = 0.01) and STS-COMP (OR 0.64, 95% CI 0.49-0.85; P = 0.002). CONCLUSIONS: Antegrade cerebral perfusion and nadir temperature ≥24°C during HCA for aortic arch repair are predictors of improved survival and neurological outcomes.

Sex-Related Differences in Patients Undergoing Thoracic Aortic Surgery.

BACKGROUND: Contemporary outcomes after surgical management of thoracic aortic disease have improved; however, the impact of sex-related differences is poorly understood. METHODS: A total of 1653 patients (498 [30.1%] female) underwent thoracic aortic surgery with hypothermic circulatory arrest between 2002 and 2017 in 10 institutions of the Canadian Thoracic Aortic Collaborative. Outcomes of interest were in-hospital death, stroke, and a modified Society of Thoracic Surgeons-defined composite for mortality or major morbidity (stroke, renal failure, deep sternal wound infection, reoperation, prolonged ventilation). Multivariable logistic regression was used to determine independent predictors of these outcomes. RESULTS: Women were older (mean±SD, 66±13 years versus 61±13 years; P<0.001), with more hypertension and renal failure, but had less coronary disease, less previous cardiac surgery, and higher ejection fraction than men. Rates of aortic dissection were similar between women and men. Rates of hemiarch, and total arch repair were similar between the sexes; however, women underwent less aortic root reconstruction including aortic root replacement, Ross, or valve-sparing root operations (29% versus 45%; P<0.001). Men experienced longer cross-clamp and cardiopulmonary bypass times, but similar durations of circulatory arrest, methods of cerebral perfusion, and nadir temperatures. Women experienced a higher rate of mortality (11% versus 7.4%; P=0.02), stroke (8.8% versus 5.5%; P=0.01), and Society of Thoracic Surgeons-defined composite end point for mortality or major morbidity (31% versus 27%; P=0.04). On multivariable analyses, female sex was an independent predictor of mortality (odds ratio, 1.81; P<0.001), stroke (odds ratio, 1.90; P<0.001), and Society of Thoracic Surgeons-defined composite end point for mortality or major morbidity (odds ratio, 1.40; P<0.001). CONCLUSIONS: Women experience worse outcomes after thoracic aortic surgery with hypothermic circulatory arrest. Further investigation is required to better delineate which measures may reduce sex-related outcome differences after complex aortic surgery.

Dual antiplatelet therapy in patients requiring urgent coronary artery bypass grafting surgery: a position statement of the Canadian Cardiovascular Society.

UNLABELLED: Acute coronary syndrome (ACS) guidelines recommend that most patients receive dual antiplatelet therapy with clopidogrel and acetylsalicylic acid (ASA) at the time of presentation to prevent recurrent ischemic events. Approximately 10% of ACS patients require coronary artery bypass grafting surgery (CABG) during the index admission. Most studies show that patients who receive ASA and clopidogrel within five days of CABG have an increase in operative bleeding. Current consensus guidelines recommend discontinuation of clopidogrel therapy at least five days before planned CABG to reduce bleeding-related events. However, high-risk individuals may require urgent surgery without delay, to reduce the risk of potentially fatal ischemic events. The present multidisciplinary position statement provides evidence- based recommendations for the optimal use of dual antiplatelet therapy to balance ischemic and bleeding risks in patients with recent ACS who may require urgent CABG. RECOMMENDATIONS: 1. All ACS patients should be considered for dual antiplatelet therapy with ASA and clopidogrel at the earliest opportunity, despite the possibility of a need for urgent CABG. 2. For patients who have received clopidogrel and ASA, and require CABG: * Those at high risk of an early fatal event (eg, with refractory ischemia despite optimal medical treatment, and with high-risk coronary anatomy (eg, severe left main stenosis with severe right coronary artery disease), should be considered for early surgery without discontinuation of clopidogrel. * In patients with a high bleeding risk (eg, previous surgery, complex surgery) who are also at high risk for an ischemic event, consideration should be given to discontinuing clopidogrel for three to five days before surgery. * Patients at a lower risk for ischemic events (most patients) should have clopidogrel discontinued five days before surgery. 3. For patients who have CABG within five days of receiving clopidogrel and ASA, the risk of major bleeding and transfusion can be minimized by applying multiple strategies before and during surgery. 4. Patients who receive clopidogrel pre-CABG for a recent ACS indication should have clopidogrel restarted after surgery to decrease the risk of recurrent ACS. 5. For patients with a recent coronary stent, the decision to continue clopidogrel until the time of surgery or to discontinue will depend on the risk and potential impact of stent thrombosis. Restarting clopidogrel after CABG will depend on whether the stented vessel was revascularized, the type of stent and the time from stent implantation. Clopidogrel should be restarted when hemostasis is assured to prevent recurrent acute ischemic events.

On-pump beating heart mitral valve repair in patients with patent bypass grafts and severe ischemic cardiomyopathy.

Re-operative mitral valve surgery in patients with poor ventricular function can be challenging especially in the presence of patent bypass grafts. We report the case of 11 patients with severe ischemic cardiomyopathy who underwent reoperative mitral valve repair through a limited right thoracotomy approach, on a non-fibrillating beating heart. All patients had their valves successfully repaired with no operative mortality and minimal morbidity. The technical aspects of the procedure are discussed, and the pertinent literature reviewed.

The combined use of extracorporeal life support and the Berlin Heart pulsatile pediatric ventricular assist device as a bridge to transplant in a toddler.

There is a very limited published material about experience with long-term pediatric mechanical circulatory support as a bridge to heart transplant. We report on a 2-year-old, 12 kg boy admitted with 2-week history of low-grade fever, ear pain, pulmonary edema, and congestive heart failure. Trans-thoracic echocardiography confirmed severe myocardial dysfunction with a left ventricular ejection fraction of 0.20 and percentage shortening of 13. After 2 days of ventilatory and inotropic support, the patient continued to deteriorate and subsequently required femoro-femoral extracorporeal life support (ECLS). This was later complicated by a progressive coagulopathy and massive bleeding. On day 17, a pulsatile pediatric paracorporeal biventricular assist device (VAD) (Berlin Heart) was implanted. The patient's condition improved significantly with all coagulopathies corrected, and the patient was extubated 21 days later. After 109 days of bi-VAD support, the patient was successfully transplanted and discharged home 45 days post transplant. Our early experience with initial ECLS bridge to VAD and subsequently to transplant was encouraging. It allowed for additional time to select the ideal organ donor and optimize the recipient's comorbid condition and multiorgan failure. VAD provides an additional armamentarium of circulatory support in pediatric patients with severe heart failure.

Mobilization and homing of bone marrow stromal cells in myocardial infarction.

OBJECTIVE: Marrow stromal cells (MSCs) contain multipotent cells, which may participate in the repair of damaged organs. We tested the hypothesis that MSCs are recruited to the heart upon myocardial infarction (MI), and play pathophysiological roles in the healing and adaptation process. METHODS: Donor MSCs from isogenic Lewis rats were harvested, multiplied and labeled with Lac Z reporter gene. Ten million labeled cells were injected intravenously into the recipient rats (n=30). One week later, 10 rats were killed to examine the distribution of the labeled MSCs. Other rats underwent either coronary artery ligations (n=14) or sham operations (n=6). The hearts were removed at various time points (1-8 weeks) and stained for beta-galactosidase activity. Phenotypes of labeled cells were identified with immunohistochemical stains. RESULTS: In rats killed at 1 week, labeled cells had homed into the bone marrow of the recipients, and none found in their hearts. In the coronary ligated hearts, labeled cells were seen in and near the infarct at all time points studied (14/14), but none in the sham operated hearts (6/6). There was evidence for myogenic differentiation. Some of these labeled cells showed positive staining for cardiomyocyte specific troponin I-c at 4 weeks, while others appeared in the vascular walls expressing smooth muscle alpha-actin. CONCLUSIONS: Following myocardial infarction, MSC's are signaled and recruited to the injured heart, where they undergo differentiation, and may participate in the pathophysiology of post-infarct remodeling, angiogenesis, and maturation of the scar. Therapeutic implantation of MSCs thus may further enhance such effects.

Timing of steroid treatment is important for cerebral protection during cardiopulmonary bypass and circulatory arrest: minimal protection of pump prime methylprednisolone.

OBJECTIVES: The contact of cardiopulmonary bypass surface and patient's blood activates systemic inflammatory response which aggravates ischemia-reperfusion injury. This study evaluates the effects of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on cerebral protection using different steroid administration protocols. METHODS: Eighteen (n=6/group) 4 week-old piglets were divided in three groups. Methylprednisolone (30 mg/kg) was administered intravenously 4 h prior to CPB in Group I, or added in pump prime in group II. Group III received no steroid. All animals were cooled to 15 degrees C followed by 100 min of DHCA, then rewarmed over 40 min and sacrificed 6 h after CPB. Post-operative weight gain, bioelectrical impedance, colloid oncotic pressure (COP) and interleukin-6 (IL-6) were evaluated. Determination of cerebral trypan blue and immunohistochemical assays of transforming growth factor (TGF)-beta1 and caspase-3 activities were performed. RESULTS: Post-operative % weight gain (13.0+/-3.8 (I) versus 26.4+/-9.9 (II) versus 22.6+/-6.4 (III), P=0.02); % bioimpedance reduction (14.5+/-8.0 (I) versus 38.3+/-13.3 (II) versus 30.5+/-8.0 (III), P=0.003); mean COP (mmHg) (14.9+/-1.8 (I) versus 10.9+/-2.0 (II) versus 6.5+/-1.8 (III), P=0.0001) and systemic IL-6 levels (pg/ml) (208.2+/-353.0 (I) versus 1562.1+/-1111.4 (II) versus 1712.3+/-533.2 (III), P=0.01) were significantly different between the groups. Spectrophotometric analysis of cerebral trypan blue (ng/g dry weight) was significantly different between the groups (0.0053+/-0.0010 (I) versus 0.0096+/-0.0026 (II) versus 0.0090+/-0.0019 (III), P=0.004). TGF-beta1 scores were 3.3+/-0.8 (I) versus 1.5+/-0.8 (II) versus 1.5+/-0.5 (III), P<0.05, groups I versus II and I versus III. Remarkable perivascular caspase-3 activity was observed in groups II and III. CONCLUSION: Different timing of steroid administration results in different inflammatory mediator response. Steroid in CPB prime is not significantly better than no steroid treatment, while systemic steroid pre-treatment significantly decreases systemic manifestation of inflammatory response and brain damage.

In vitro preprogramming of marrow stromal cells for myocardial regeneration.

BACKGROUND: We have previously reported that marrow stromal stem cells (MSCs), when implanted into myocardium, can undergo milieu-dependent differentiation to express phenotypes similar to the cells in the immediate microenvironment. We tested the hypothesis that by in vitro preprogramming of MSCs, we may be able to guide their differentiation to express a therapeutically desirable phenotype that is different from those in their microenvironment. METHODS: MSCs were isolated from isogenic Lewis rats, culture expanded, and labeled with beta-gal using retrovirus carrying the lac-Z gene. A subset of the transfected MSCs was then treated with 5-aza-2'deoxycytidine (5-aza). Three weeks after the left ventricles were cryoinjured, either 5-aza-pretreated (n = 10) or untreated (n = 8) MSCs were injected into the myocardial scar. The hearts were harvested 4 to 8 weeks later and stained immunohistochemically for phenotypic markers. RESULTS: The labeled MSCs within the scars that were 5-aza pretreated appeared to be morphologically distinct from the untreated ones. The treated cells (8/10 rats) appeared more myotube-like, with elongated nuclei, linearly aligned with one another, and stained positive for the cardiomyocyte-specific marker troponin I-C. Untreated MSCs (5/8 rats), in contrast, were poorly differentiated, and some appeared to express other phenotypes seen in the scar tissue. CONCLUSIONS: Our findings indicate that in cellular cardiomyoplasty using MSCs, one may select different strategies to achieve specific therapeutic goals. By milieu-dependent differentiation, unmodified MSCs may augment myocardial angiogenesis and myogenesis, whereas converting scar into myogenic tissue may be facilitated by preprogramming of MSCs before implantation.

Xenotransplant cardiac chimera: immune tolerance of adult stem cells.

BACKGROUND: Bone marrow stromal cells have been shown to engraft into xenogeneic fetal recipients. In view of the potential clinical utility as an alternative source for cellular and gene therapies, we studied the fate of xenogeneic marrow stromal cells after their systemic transplantation into fully immunocompetent adult recipients without immunosuppression. METHODS: Bone marrow stromal cells were isolated from C57B1/6 mice and retrovirally transduced with LacZ reporter gene for cell labeling. We then injected 6 x 10(6) labeled cells into immunocompetent adult Lewis rats. One week later, the recipient animals underwent coronary artery ligation and were sacrificed at various time points ranging from 1 day to 12 weeks after ligation. Hearts, blood, and bone marrow samples were collected for histologic and immunohistochemical studies. RESULTS: Labeled mice cells engrafted into the bone marrow cavities of the recipient rats for at least 13 weeks after transplantation without any immunosuppression. On the other hand, circulating mice cells were positive only for the animals with 1-day-old myocardial infarction. At various time points, numerous mice cells could be found in the infarcted myocardium that were not seen before coronary ligation. Some of these cells subsequently showed positive staining for cardiomyocyte specific proteins, while other labeled cells participated in angiogenesis in the infarcted area. CONCLUSIONS: The marrow stromal cells are adult stem cells with unique immunologic tolerance allowing their engraftment into a xenogeneic environment, while preserving their ability to be recruited to an injured myocardium by way of the bloodstream and to undergo differentiation to form a stable cardiac chimera.