Prediction of acute kidney injury risk after cardiac surgery: using a hybrid machine learning algorithm.

BACKGROUND: Acute kidney injury (AKI) is a serious complication after cardiac surgery. We derived and internally validated a Machine Learning preoperative model to predict cardiac surgery-associated AKI of any severity and compared its performance with parametric statistical models. METHODS: We conducted a retrospective study of adult patients who underwent major cardiac surgery requiring cardiopulmonary bypass between November 1st, 2009 and March 31st, 2015. AKI was defined according to the KDIGO criteria as stage 1 or greater, within 7 days of surgery. We randomly split the cohort into derivation and validation datasets. We developed three AKI risk models: (1) a hybrid machine learning (ML) algorithm, using Random Forests for variable selection, followed by high performance logistic regression; (2) a traditional logistic regression model and (3) an enhanced logistic regression model with 500 bootstraps, with backward variable selection. For each model, we assigned risk scores to each of the retained covariate and assessed model discrimination (C statistic) and calibration (Hosmer-Lemeshow goodness-of-fit test) in the validation datasets. RESULTS: Of 6522 included patients, 1760 (27.0%) developed AKI. The best performance was achieved by the hybrid ML algorithm to predict AKI of any severity. The ML and enhanced statistical models remained robust after internal validation (C statistic = 0.75; Hosmer-Lemeshow p = 0.804, and AUC = 0.74, Hosmer-Lemeshow p = 0.347, respectively). CONCLUSIONS: We demonstrated that a hybrid ML model provides higher accuracy without sacrificing parsimony, computational efficiency, or interpretability, when compared with parametric statistical models. This score-based model can easily be used at the bedside to identify high-risk patients who may benefit from intensive perioperative monitoring and personalized management strategies.

Derivation and validation of a clinical model to predict death or cardiac hospitalizations while on the cardiac surgery waitlist.

BACKGROUND: Waitlist management is a global challenge. For patients with severe cardiovascular diseases awaiting cardiac surgery, prolonged wait times are associated with unplanned hospitalizations. To facilitate evidence-based resource allocation, we derived and validated a clinical risk model to predict the composite outcome of death and cardiac hospitalization of patients on the waitlist for cardiac surgery. METHODS: We used the CorHealth Ontario Registry and linked ICES health care administrative databases, which have information on all Ontario residents. We included patients 18 years or older who waited at home for coronary artery bypass grafting, valvular or thoracic aorta surgeries between 2008 and 2019. The primary outcome was death or an unplanned cardiac hospitalizaton, defined as nonelective admission for heart failure, myocardial infarction, unstable angina or endocarditis. We randomly divided two-thirds of these patients into derivation and one-third into validation data sets. We derived the model using a multivariable Cox proportional hazard model with backward stepwise variable selection. RESULTS: Among 62 375 patients, 41 729 patients were part of the derivation data set and 20 583 were part of the validation data set. Of the total, 3033 (4.9%) died or had an unplanned cardiac hospitalization while waiting for surgery. The area under the curve of our model at 15, 30, 60 and 89 days was 0.85, 0.82, 0.81 and 0.80, respectively, in the derivation cohort and 0.83, 0.80, 0.78 and 0.78, respctively, in the validation cohort. The model calibrated well at all time points. INTERPRETATION: We derived and validated a clinical risk model that provides accurate prediction of the risk of death and unplanned cardiac hospitalization for patients on the cardiac surgery waitlist. Our model could be used for quality benchmarking and data-driven decision support for managing access to cardiac surgery.

Clinical Impact of Changes in Left Ventricular Function After Aortic Valve Replacement: Analysis From 3112 Patients.

BACKGROUND: Our objectives were to identify correlates of mortality and congestive heart failure after aortic valve replacement (AVR) according to preoperative left ventricular (LV) function and to describe the incidence, time course, and correlates of LV recovery and mass regression postoperatively. METHODS AND RESULTS: A total of 3112 patients with AVR were assessed in a follow-up clinic with echocardiography (median follow-up, 6.0 years). At operation, their mean age was 67.8±13.4 years, one third were female, and 29% had LV dysfunction (ejection fraction <50%). In severe patients with severe aortic stenosis and LV dysfunction, transaortic valve mean pressure gradient <40 mm Hg, longer cardiopulmonary bypass duration, and prosthesis-patient mismatch (indexed effective orifice area ≤0.85 cm(2)/m(2)) were independent correlates of the composite outcome of death or congestive heart failure after AVR. In patients with severe aortic regurgitation and LV dysfunction, older age and higher preoperative LV mass were identified. LV recovery correlated with better survival and freedom from heart failure in patients with aortic stenosis. Maximum LV mass regression took 24 months in patients with aortic stenosis and nearly 5 years with aortic regurgitation; independent correlates included smaller LV end-systolic diameter in patients with aortic stenosis and low New York Heart Association class with aortic regurgitation. CONCLUSIONS: Incomplete LV recovery, prosthesis-patient mismatch, low transaortic valve pressure gradient, and higher LV mass are associated with increased mortality or heart failure after AVR in patients with LV dysfunction. Higher LV end-systolic diameter and symptoms correlate with less LV mass regression, which takes at least 2 years. These findings help surgeons and cardiologists refine the indications, timing, prognostication, and follow-up of patients before and after AVR.

Reoperation of left heart valve bioprostheses according to age at implantation.

BACKGROUND: Evidence supporting the use of bioprostheses for heart valve replacement in young adults is accumulating. However, reoperation data, which may help guide clinical decision making in young patients, remains poorly defined in the literature. METHODS AND RESULTS: We examined the need for reoperation in 3975 patients who underwent first-time bioprosthetic aortic valve replacement (AVR) (n=3152) or mitral valve replacement (MVR) (n=823). There were 895 patients below the age of 60 years at bioprosthesis implant (AVR, n=636; MVR, n=259). The median interval to reoperation of contemporary, stented aortic bioprostheses was 7.74 years (95% CI 7.28 to 9.97 years) in patients less than 40 years, and 12.93 years (95% CI 11.10 to 15.76 years) in patients between 40 and 60 years of age. Multivariable risk factors associated with reoperation following bioprosthetic AVR include age (hazard ratio [HR] 0.94 per year, 95% CI 0.91 to 0.96, P<0.001) and concomitant coronary artery bypass grafting (HR 0.34, 95% CI 0.11 to 0.99, P=0.04). The median interval to reoperation of contemporary mitral bioprostheses was 8.11 years (95% CI 5.79 to 16.50 years) in patients less than 40 years, and 10.14 years (95% CI 8.64 to 11.14 years) in patients between 40 and 60 years of age. As for AVR, age (HR 0.96 per year, 95% CI 0.95 to 0.98, P<0.001) and concomitant coronary artery bypass grafting (HR 0.55, 95% CI 0.32 to 0.93, P=0.03) were associated with decreased reoperation risk following bioprosthetic MVR. CONCLUSIONS: These data constitute clinically relevant age-specific prognostic information regarding reoperation in young patients, who may wish to select a bioprosthesis at initial left heart valve replacement.

Aortic Valve Repair Decreases Risks of VRE in AI at 10 Years: A Propensity Score-Matched Analysis.

BACKGROUND: Aortic valve repair (AVr) has emerged as a feasible and effective alternative to AV replacement (AVR) in patients with aortic insufficiency (AI); however, little data exist comparing outcomes. Thus, the objective of this study was to compare early and long-term valve-related complications between AVr and AVR in the treatment of AI. METHODS: This was a single-center, retrospective study of all patients (n = 417) undergoing AVr (n = 264) or AVR (n = 153) for primary AI. Propensity matching using a 1:1 greedy matching algorithm identified 140 patients using 6 covariates (age, sex, left ventricular function, size, presence of aortopathy, and urgency of operation) for comparison. The primary outcome was a composite of all valve-related events (VREs), including endocarditis, myocardial infarction stroke, transient ischemic attack, thromboembolisms, bleeding, and AV reoperation. VREs were defined as per published guidelines. Survival and freedom from VREs were reported using the Kaplan-Meier method. RESULTS: Propensity matching identified 70 well-matched pairs with no major differences in baseline demographics, comorbidities, or AI severity (P = .57). Perioperative outcomes showed no significant differences in VREs (AVR 8 vs AVr 7; P = .78) or mortality (AVR 3 vs AVr 1; P = .62). Event-free survival from the primary outcome at 10 years was significantly better after AVr than after AVR (82% vs 68%; P = .024), with no significant differences in 10-year overall survival between groups (82% vs 72%; P = .29). No significant differences in AI severity (P = .07) or reoperation rate (P = .44) were detected between groups. CONCLUSIONS: This study demonstrated a lower long-term risk of VREs with repair compared with replacement, with low mortality and comparable durability. Further prospective randomized control trials are necessary to formally compare outcomes and determine superiority.

Derivation and validation of a clinical risk score to predict death among patients awaiting cardiac surgery in Ontario, Canada: a population-based study.

BACKGROUND: Surgical delay may result in unintended harm to patients needing cardiac surgery, who are at risk for death if their condition is left untreated. Our objective was to derive and internally validate a clinical risk score to predict death among patients awaiting major cardiac surgery. METHODS: We used the CorHealth Ontario Registry and linked ICES health administrative databases with information on all Ontario residents to identify patients aged 18 years or more who were referred for isolated coronary artery bypass grafting (CABG), valvular procedures, combined CABG-valvular procedures or thoracic aorta procedures between Oct. 1, 2008, and Sept. 30, 2019. We used a hybrid modelling approach with the random forest method for initial variable selection, followed by backward stepwise logistic regression modelling for clinical interpretability and parsimony. We internally validated the logistic regression model, termed the CardiOttawa Waitlist Mortality Score, using 200 bootstraps. RESULTS: Of the 112 266 patients referred for cardiac surgery, 269 (0.2%) died while awaiting surgery (118/72 366 [0.2%] isolated CABG, 81/24 461 [0.3%] valvular procedures, 63/12 046 [0.5%] combined CABG-valvular procedures and 7/3393 [0.2%] thoracic aorta procedures). Age, sex, surgery type, left main stenosis, Canadian Cardiovascular Society classification, left ventricular ejection fraction, heart failure, atrial fibrillation, dialysis, psychosis and operative priority were predictors of waitlist mortality. The model discriminated (C-statistic 0.76 [optimism-corrected 0.73]). It calibrated well in the overall cohort (Hosmer-Lemeshow p = 0.2) and across surgery types. INTERPRETATION: The CardiOttawa Waitlist Mortality Score is a simple clinical risk model that predicts the likelihood of death while awaiting cardiac surgery. It has the potential to provide data-driven decision support for managing access to cardiac care and preserve system capacity during the COVID-19 pandemic, the recovery period and beyond.

Long-term clinical and hemodynamic performance of the Hancock II versus the Perimount aortic bioprostheses.

BACKGROUND: The Medtronic Hancock II and the Carpentier-Edwards Perimount are among the world's most commonly used aortic bioprostheses. However, a direct comparison of their clinical performance is lacking. To minimize biases inherent to between-center comparisons, we examined these prostheses within a large, contemporary, single-center cohort. METHODS AND RESULTS: Between 1990 and 2007, 1659 patients (mean age, 73.1±9.3 years) underwent aortic valve replacement with either the Hancock II (N=1021) or the Perimount (N=638). Patients were prospectively followed-up with serial clinic visits and echocardiograms for up to 16 years (mean, 5.0±3.3 years). There was no significant difference in aortic root size preoperatively (P=0.7). Aortic root enlargement was more commonly performed with the Perimount (P<0.001), and the manufacturer valve size of the implanted prosthesis was larger with the Hancock II (P<0.001). Postoperatively, peak and mean transprosthesis gradients were higher for the Hancock II (32.7±0.7 and 16.0±0.3 mm Hg, respectively) than for the Perimount (24.9±0.7 and 13.4±0.4 mm Hg, respectively; P<0.001). However, no difference in left ventricular mass regression was observed at late follow-up (P=0.9). Unadjusted 10-year survival was 59.4%±2.4% for the Hancock II and 70.2%±3.8% for the Perimount (P=0.07). Multivariable predictors of survival did not include prosthesis type (P=0.2). CONCLUSIONS: For the same manufacturer valve size, the Perimount is larger, which may warrant enlarging the aortic root more often, and it is associated with better hemodynamics than the Hancock II. These differences do not impact survival or left ventricular mass regression, and the long-term clinical performances of the Hancock II and Perimount bioprostheses are equivalent.

Aspirin plus clopidogrel versus aspirin alone after coronary artery bypass grafting: the clopidogrel after surgery for coronary artery disease (CASCADE) Trial.

BACKGROUND: clopidogrel inhibits intimal hyperplasia in animal studies and therefore may reduce saphenous vein graft (SVG) intimal hyperplasia after coronary artery bypass grafting. The Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) study was undertaken to evaluate whether the addition of clopidogrel to aspirin inhibits SVG disease after coronary artery bypass grafting, as assessed at 1 year by intravascular ultrasound. METHODS AND RESULTS: in this double-blind phase II trial, 113 patients undergoing coronary artery bypass grafting with SVGs were randomized to receive aspirin 162 mg plus clopidogrel 75 mg daily or aspirin 162 mg plus placebo daily for 1 year. The primary outcome was SVG intimal hyperplasia (mean intimal area) as determined by intravascular ultrasound at 1 year. Secondary outcomes were graft patency, major adverse cardiovascular events, and major bleeding. One-year intravascular ultrasound and coronary angiography were performed in 92 patients (81.4%). At 1 year, SVG intimal area did not differ significantly between the 2 groups (4.1 ± 2.0 versus 4.5 ± 2.1 mm(2), aspirin-clopidogrel versus aspirin-placebo, P=0.44). Overall 1-year graft patency was 95.2% in the aspirin-clopidogrel group compared with 95.5% in the aspirin-placebo group (P=0.90), and SVG patency was 94.3% in the aspirin-clopidogrel group versus 93.2% in the aspirin-placebo group (P=0.69). Freedom from major adverse cardiovascular events at 1 year was 92.9 ± 3.4% in the aspirin-clopidogrel group and 91.1 ± 3.8% in the aspirin-placebo group (P=0.76). The incidence of major bleeding at 1 year was similar for the 2 groups (1.8% versus 0%, aspirin-clopidogrel versus aspirin-placebo, P=0.50). CONCLUSIONS: compared with aspirin monotherapy, the combination of aspirin plus clopidogrel did not significantly reduce the process of SVG intimal hyperplasia 1 year after coronary artery bypass grafting.

Disability-free survival after major cardiac surgery: a population-based retrospective cohort study.

BACKGROUND: Cardiovascular research has traditionally been dedicated to "tombstone" outcomes, with little attention dedicated to the patient's perspective. We evaluated disability-free survival as a patient-defined outcome after cardiac surgery. METHODS: We conducted a retrospective cohort study of patients aged 40 years and older who underwent coronary artery bypass grafting (CABG) or single or multiple valve (aortic, mitral, tricuspid) surgery in Ontario between Oct. 1, 2008, and Dec. 31, 2016. The primary outcome was disability (a composite of stroke, 3 or more nonelective hospital admissions and admission to a long-term care facility) within 1 year after surgery. We assessed the procedure-specific risk of disability using cumulative incidence functions, and the relative effect of covariates on the subdistribution hazard using Fine and Gray models. RESULTS: The study included 72 824 patients. The 1-year incidence of disability and death was 2431 (4.6%) and 1839 (3.5%) for CABG, 677 (6.5%) and 539 (5.2%) for single valve, 118 (9.0%) and 140 (10.7%) for multiple valve, 718 (9.0%) and 730 (9.2%) for CABG and single valve, and 87 (13.1%) and 94 (14.1%) for CABG and multiple valve surgery, respectively. With CABG as the reference group, the adjusted hazard ratios for disability were 1.34 (95% confidence interval [CI] 1.21-1.48) after single valve, 1.43 (95% CI 1.18-1.75) after multiple valve, 1.38 (95% CI 1.26-1.51) after CABG and single valve, and 1.78 (95% CI 1.43-2.23) after CABG and multiple valve surgery. Combined CABG and multiple valve surgery, heart failure, creatinine 180 µmol/L or greater, alcohol use disorder, dementia and depression were independent risk factors for disability. INTERPRETATION: The cumulative incidence of disability was lowest after CABG and highest after combined CABG and multiple valve surgery. Our findings point to a need for models that predict personalized disability risk to enable better patient-centred care.

Impact of surgeon and anaesthesiologist sex on patient outcomes after cardiac surgery: a population-based study.

BACKGROUND: Effective teamwork between anaesthesiologists and surgeons is essential for optimising patient safety in the cardiac operating room. While many factors may influence the relationship between these two physicians, the role of sex and gender have yet to be investigated. OBJECTIVES: We sought to determine the association between cardiac physician team sex discordance and patient outcomes. DESIGN: We performed a population-based, retrospective cohort study. PARTICIPANTS AND SETTING: Adult patients who underwent coronary artery bypass grafting (CABG) and/or aortic, mitral or tricuspid valve surgery between 2008 and 2018 in Ontario, Canada. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was all-cause 30-day mortality. Secondary outcomes included major adverse cardiovascular events at 30 days and hospital and intensive care unit lengths of stay (LOS). Mixed effects logistic regression was used for categorical outcomes and Poisson regression for continuous outcomes. RESULTS: 79 862 patients underwent cardiac surgery by 98 surgeons (11.2% female) and 279 anaesthesiologists (23.3% female); 19 893 (24.9%) were treated by sex-discordant physician teams. Physician sex discordance was not associated with overall patient mortality or LOS; however, patients who underwent isolated CABG experienced longer hospital LOS when treated by an all-male physician team as compared with an all-female team (adjusted OR=1.07; p=0.049). When examining the impact of individual physician sex, the length of hospital stay was longer when isolated CABG procedures were attended by a male surgeon (OR=1.10; p=0.004) or anaesthesiologist (OR=1.02; p=0.01). CONCLUSIONS: Patient mortality and length of stay after cardiac surgery may vary by sex concordance of the attending surgeon-anaesthesiologist team. Further research is needed to examine the underlying mechanisms of these observed relationships.

Derivation of Patient-Defined Adverse Cardiovascular and Noncardiovascular Events Through a Modified Delphi Process.

Importance: There is little evidence to support patient-centered outcomes in patients with cardiovascular disease. Objective: To derive patient-defined adverse cardiovascular and noncardiovascular events (PACE) through a consensus-based process. Design, Setting, and Participants: This pan-Canadian, consensus-based, qualitative study used an iterative Delphi method to achieve consensus within a 35-member panel consisting of patients with cardiovascular diseases and their caregivers and clinicians. The process included 4 rounds of online questionnaires, followed by an in-person final consensus meeting. Data analysis was performed in September 2019. Main Outcomes and Measures: Defining PACE as a 5-item composite outcome. Results: Thirty-five potential panelists consented to participate, including 11 clinicians (8 men [73%]) and 24 patients and caregivers (13 men [54%]). Twenty-nine (83%), 28 (80%), 26 (74%), and 23 (66%) of the panelists participated in each of respective the online rounds. A shortlist of 11 patient-defined items was further refined at the in-person meeting, which 20 of the panelists attended. The PACE definition that was decided through the consensus process was a composite of severe stroke necessitating hospitalization for 14 days or longer or inpatient rehabilitation, ventilator dependence, new onset or worsening heart failure, nursing home admission, or new onset dialysis. Conclusions and Relevance: This study defined PACE as a versatile, patient-centered outcome through a consensus process with input from patients, caregivers, and clinicians. Given the paucity of patient-centered outcomes in cardiovascular research, PACE may be considered as a potential outcome after methodological evaluation of its reliability.

Minimally invasive coronary artery bypass grafting: dual-center experience in 450 consecutive patients.

BACKGROUND: Minimally invasive coronary artery bypass grafting (MICS CABG) is a novel coronary operation that does not require infrastructure and is potentially available to all cardiac surgeons. It aims at decreasing the invasiveness of conventional CABG while preserving the applicability and durability of surgical revascularization. We examined the feasibility and safety of MICS CABG in the first large series of this operation to date. METHODS AND RESULTS: All myocardial territories are accessed via a 4- to 6-cm left fifth intercostal thoracotomy. An apical positioner and epicardial stabilizer are introduced into the chest through the subxyphoid and left seventh intercostal spaces, respectively. The left internal thoracic artery is used to graft the left anterior descending artery, and radial artery or saphenous vein segments are used to graft the lateral and inferior myocardial territories. Proximal anastomoses are performed directly onto the aorta or from the left internal thoracic artery as a T-graft. In the first 450 consecutive MICS CABG procedures at our 2 centers, mean+/-SD age was 62.3+/-10.7 years and 123 patients were female (27%). The average number of grafts was 2.1+/-0.7, with complete revascularization in 95% of patients. There were 34 patients in whom cardiopulmonary bypass was used (7.6%), 17 conversions to sternotomy (3.8%), and 10 reinterventions for bleeding (2.2%). Perioperative mortality occurred in 6 patients (1.3%). CONCLUSIONS: MICS CABG is feasible and has excellent procedural and short-term outcomes. This operation could potentially make multivessel minimally invasive coronary surgery safe, effective, and more widely available.

An acellular matrix-bound ligand enhances the mobilization, recruitment and therapeutic effects of circulating progenitor cells in a hindlimb ischemia model.

Circulating progenitor cells home to and engraft to sites of ischemia, mediated in part by the adhesion molecule L-selectin; however, accumulation in tissues such as the heart is low. In this study, an acellular collagen-based matrix containing sialyl Lewis(X) (sLe(X)), which binds L-selectin, was developed in order to enhance the endogenous progenitor cell therapeutic response. Its effect on progenitor cells and angiogenesis were assessed in vitro and using a hindlimb ischemia model with rats. In culture, the sLe(X)-collagen matrix recruited more CD133(+)CD34(+)L-selectin(+) cells than collagen-only matrix, with adhesion mediated by L-selectin binding. Increased angiogenic/chemotactic cytokine production and improved resistance to apoptosis appeared in cells cultured on sLe(X)-collagen matrix. In vivo, mobilization of endogenous circulating progenitor cells was increased, and greater recruitment of these and systemically injected human peripheral blood CXCR4(+)L-selectin(+) cells to sLe(X)-collagen treated limbs was observed compared to collagen-only. This condition was associated with differences in angiogenic/chemotactic cytokine levels, with greater arteriole density and increased perfusion in sLe(X)-collagen treated hindlimbs. With these factors taken together, we demonstrated that an acellular matrix-bound ligand approach can enhance the mobilization, recruitment, and therapeutic effects of endogenous and/or transplanted progenitor cells, possibly through paracrine and antiapoptotic mechanisms, and could be used to improve cell-based regenerative therapies.

Frequency and surgical management of complex posterior leaflet prolapse of the mitral valve.

BACKGROUND AND AIM OF THE STUDY: Isolated posterior leaflet prolapse of the mitral valve may present with more complex anatomy than limited middle scallop prolapse (P2). The study aim was to describe the incidence and surgical management of extensive or commissural posterior leaflet prolapse, in addition to long-term outcomes following repair. METHODS: Between October 2001 and May 2008, among 481 patients operated on for mitral valve prolapse, 201 consecutive patients underwent mitral valve repair for isolated posterior leaflet prolapse. Of the latter patients, only 81 (40%) had limited P2 prolapse, while the remaining 120 (60%) showed complex posterior leaflet prolapse, including either extensive (n = 105) or commissural (n = 15) prolapse. Extensive leaflet prolapse was treated with aggressive leaflet resection and sliding plasty, combined with a longitudinal annular plication using polytetrafluoroethylene running sutures. Commissural prolapse was repaired with an edge-to-edge technique or commissuroplasty. The clinical and echocardiographic follow up was complete for all patients, and extended up to 6.8 years (mean 2.4 +/- 1.9 years). RESULTS: There was no hospital mortality. Repair was successful in 200 patients (99%), who showed no or trivial mitral regurgitation (MR) intraoperatively. The five-year freedom from recurrent MR (grade > 1+) was 91.5 +/- 4.2% in patients with isolated P2 prolapse, compared to 98.8 +/- 1.2% in patients with complex posterior leaflet prolapse (p = 0.07). The repair of complex posterior leaflet prolapse was also similar to that of isolated P2 prolapse with regard to five-year freedom from reoperation (98.9 +/- 5.9% versus 100%; p = 0.4), and survival (92.1 +/- 3.3% versus 88.9 +/- 8.0%; p = 0.9). CONCLUSION: In the present series, posterior leaflet prolapse offered more complexity than usually reported, requiring surgical skills beyond simple quadrangular resection. However, the surgical approach, which typically involved extensive leaflet resection and sliding plasty, offered high repair rates and acceptable durability, considering the initial severity of the prolapse anatomy.

The Impact of Preoperative Risk on the Association between Hypotension and Mortality after Cardiac Surgery: An Observational Study.

BACKGROUND: Despite steady improvements in cardiac surgery-related outcomes, our understanding of the physiologic mechanisms leading to perioperative mortality remains incomplete. Intraoperative hypotension is an important risk factor for mortality after noncardiac surgery but remains relatively unexplored in the context of cardiac surgery. We examined whether the association between intraoperative hypotension and in-hospital mortality varied by patient and procedure characteristics, as defined by the validated Cardiac Anesthesia Risk Evaluation (CARE) mortality risk score. METHODS: We conducted a retrospective cohort study of consecutive adult patients who underwent cardiac surgery requiring cardiopulmonary bypass (CPB) from November 2009-March 2015. Those who underwent off-pump, thoracic aorta, transplant and ventricular assist device procedures were excluded. The primary outcome was in-hospital mortality. Hypotension was categorized by mean arterial pressure (MAP) of <55 and between 55-64 mmHg before, during and after CPB. The relationship between hypotension and death was modeled using multivariable logistic regression in the intermediate and high-risk groups. RESULTS: Among 6627 included patients, 131 (2%) died in-hospital. In-hospital mortality in patients with CARE scores of 1, 2, 3, 4 and 5 was 0 (0%), 7 (0.3%), 35 (1.3%), 41 (4.6%) and 48 (13.6%), respectively. In the intermediate-risk group (CARE = 3-4), MAP < 65 mmHg post-CPB was associated with increased odds of death in a dose-dependent fashion (adjusted OR 1.30, 95% CI 1.13-1.49, per 10 min exposure to MAP < 55 mmHg, p = 0.002; adjusted OR 1.18 [1.07-1.30] per 10 min exposure to MAP 55-64 mmHg, p = 0.001). We did not observe an association between hypotension and mortality in the high-risk group (CARE = 5). CONCLUSIONS: Post-CPB hypotension is a potentially modifiable risk factor for mortality in intermediate-risk patients. Our findings provide impetus for clinical trials to determine if hemodynamic goal-directed therapies could improve survival in these patients.

Derivation and Validation of a Clinical Model to Predict Intensive Care Unit Length of Stay After Cardiac Surgery.

Background Across the globe, elective surgeries have been postponed to limit infectious exposure and preserve hospital capacity for coronavirus disease 2019 (COVID-19). However, the ramp down in cardiac surgery volumes may result in unintended harm to patients who are at high risk of mortality if their conditions are left untreated. To help optimize triage decisions, we derived and ambispectively validated a clinical score to predict intensive care unit length of stay after cardiac surgery. Methods and Results Following ethics approval, we derived and performed multicenter valida tion of clinical models to predict the likelihood of short (≤2 days) and prolonged intensive care unit length of stay (≥7 days) in patients aged ≥18 years, who underwent coronary artery bypass grafting and/or aortic, mitral, and tricuspid value surgery in Ontario, Canada. Multivariable logistic regression with backward variable selection was used, along with clinical judgment, in the modeling process. For the model that predicted short intensive care unit stay, the c-statistic was 0.78 in the derivation cohort and 0.71 in the validation cohort. For the model that predicted prolonged stay, c-statistic was 0.85 in the derivation and 0.78 in the validation cohort. The models, together termed the CardiOttawa LOS Score, demonstrated a high degree of accuracy during prospective testing. Conclusions Clinical judgment alone has been shown to be inaccurate in predicting postoperative intensive care unit length of stay. The CardiOttawa LOS Score performed well in prospective validation and will complement the clinician's gestalt in making more efficient resource allocation during the COVID-19 period and beyond.

Sex Differences in Long-Term Survival After Major Cardiac Surgery: A Population-Based Cohort Study.

Background Little attention has been paid to the importance of sex in the long-term prognosis of patients undergoing cardiac surgery. Methods and Results We conducted a retrospective cohort study of Ontario residents, aged ≥40 years, who underwent coronary artery bypass grafting (CABG) and/or aortic, mitral, or tricuspid valve surgery between October 1, 2008, and December 31, 2016. The primary outcome was all-cause mortality. The mortality rate in each surgical group was calculated using the Kaplan-Meier method. The risk of death was assessed using multivariable Cox proportional hazard models. Sex-specific mortality risk factors were identified using multiplicative interaction terms. A total of 72 824 patients were included in the study (25% women). The median follow-up period was 5 (interquartile range, 3-7) years. The long-term age-standardized mortality rate was lowest in patients who underwent isolated CABG and highest among those who underwent combined CABG/multiple valve surgery. Women had significantly higher age-standardized mortality rate than men after CABG and combined CABG/mitral valve surgery. Men had lower rates of long-term mortality than women after isolated mitral valve repair, whereas women had lower rates of long-term mortality than men after isolated mitral valve replacement. We observed a statistically significant association between female sex and long-term mortality after adjustment for key risk factors. Conclusions Female sex was associated with long-term mortality after cardiac surgery. Perioperative optimization and long-term follow-up should be tailored to younger women with a history of myocardial infarction and percutaneous coronary intervention and older men with a history of chronic obstructive pulmonary disease and depression.

Very long-term survival implications of heart valve replacement with tissue versus mechanical prostheses in adults <60 years of age.

BACKGROUND: Several centers favor replacing a diseased native heart valve with a tissue rather than a mechanical prosthesis, even in younger adult patients. However, long-term data supporting this approach are lacking. We examined the survival implications of selecting a tissue versus a mechanical prosthesis at initial left-heart valve replacement in a cohort of adults <60 years of age who were followed for over 20 years. METHODS AND RESULTS: Comorbid and procedural data were available from 6554 patients who underwent valve replacement at our institution over the last 35 years. Of these, 1512 patients contributed follow-up data beyond 20 years, of whom 567 were adults <60 years of age at first left-heart valve operation (mean survivor follow-up, 24.0+/-3.1 years). Late outcomes were examined with Cox regression. Valve reoperation, often for prostheses that are no longer commercially available, occurred in 89% and 84% of patients by 20 years after tissue aortic and mitral valve replacement, respectively, and was associated with a mortality of 4.3%. There was no survival difference between patients implanted with a tissue versus a mechanical prosthesis at initial aortic valve replacement (hazard ratio 0.95; 95% CI: 0.7, 1.3; P=0.7). For mitral valve replacement patients, long-term survival was poorer than after aortic valve replacement (hazard ratio 1.4; 95% CI: 1.1, 1.8; P=0.003), but again no detrimental effect was associated with use of a tissue versus a mechanical prosthesis (hazard ratio 0.9; 95% CI 0.5, 1.4; P=0.5). CONCLUSIONS: In our experience, selecting a tissue prosthesis at initial operation in younger adults does not negatively impact survival into the third decade of follow-up, despite the risk of reoperation.

Eight-year follow-up of the Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) trial.

OBJECTIVE: In this 8 years' follow-up study, we evaluated the long-term outcomes of the addition of clopidogrel to aspirin during the first year after coronary artery bypass grafting, versus aspirin plus placebo, with respect to survival, major adverse cardiac, or major cerebrovascular events, including revascularization, functional status, graft patency, and native coronary artery disease progression. METHODS: In the initial Clopidogrel After Surgery for Coronary Artery Disease trial, 113 patients were randomized to receive either daily clopidogrel (n = 56) or placebo (n = 57), in addition to aspirin, in a double-blind fashion for 1 year after coronary artery bypass grafting. All patients were re-evaluated to collect long-term clinical data. Surviving patients with a glomerular filtration rate > 30 mL/min were asked to undergo a coronary computed tomography angiogram to evaluate the late saphenous vein graft patency and native coronary artery disease progression. RESULTS: At a median follow-up of 7.6 years, survival rate was 85.5% ± 3.8% (P = .23 between the 2 groups). A trend toward enhanced freedom from all-cause death or major adverse cardiac or cerebrovascular events, including revascularization, was observed in the aspirin-clopidogrel group (P = .11). No difference in functional status or freedom from angina was observed between the 2 groups (P > .57). The long-term patency of saphenous vein graft was 89.11% in the aspirin-clopidogrel group versus 91.23% in the aspirin-placebo group (P = .79). A lower incidence of moderate to severe native disease progression was observed in the aspirin-clopidogrel group versus the aspirin-placebo group (7 out of 122 vs 13 out of 78 coronary segments that showed progression, respectively [odds ratio, 0.3 ± 0.2; 95% confidence interval, 0.1-0.8; P = .02]). CONCLUSIONS: At 8 years' follow-up, the addition of clopidogrel to aspirin during the first year after coronary artery bypass grafting exhibited a lower incidence of moderate to severe progression of native coronary artery disease and a trend toward higher freedom from major adverse cardiac or cerebrovascular events, including revascularization, or death in the aspirin-clopidogrel group. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00228423.

Long-term outcomes after valve replacement for low-gradient aortic stenosis: impact of prosthesis-patient mismatch.

BACKGROUND: The long-term outcomes of patients with low-gradient aortic stenosis (LGAS) after aortic valve replacement (AVR) are poorly defined. The purpose of this study was to define the long-term outcomes of LGAS patients after AVR and to evaluate the potential impact of prosthesis-patient mismatch (PPM) in these patients. METHODS AND RESULTS: A cohort of 664 patients undergoing AVR for aortic stenosis after 1990 were followed-up prospectively with annual clinical assessment and echocardiography (total follow-up 3447 patient-years; mean follow-up 5.2+/-3.3 years). LGAS was defined as an aortic valve area <1.2 cm2, a mean transvalvular pressure gradient <40 mm Hg, and a left ventricular (LV) ejection fraction <50%, and was present in 79 patients. Rates and correlates of survival, freedom from congestive heart failure (CHF), and LV mass regression after AVR were determined using multivariate regression methods. Ten-year survival and freedom from CHF after AVR were 72.7+/-7.5% and 68.2+/-9.5%, respectively, for patients with LGAS, compared with 89.6+/-1.8% and 84.1+/-4.2% for patients without LGAS (hazard ratio [HR] for death and postoperative CHF, 3.1+/-1.1 and 2.7+/-0.9, respectively; P<0.01). In LGAS patients, PPM, defined as an indexed effective orifice area < or = 0.85 cm2/m2, was independently associated with increased rates of CHF (HR, 3.6+/-2.2; P=0.039), impaired LV mass regression (P=0.037), and a trend toward increased late mortality (HR, 3.0+/-1.9; P=0.084). CONCLUSIONS: Patients with LGAS have worse long-term outcomes after AVR compared with patients without LGAS. PPM adversely affects the long-term outcomes of LGAS patients and should be avoided in this population.