Considerations & challenges of mitral valve repair in females: diagnosis, pathology, and intervention.

PURPOSE OF REVIEW: Disparities in mitral valve (MV) repair outcomes exist between men and women. This review highlights sex-specific differences in MV disease aetiology, diagnosis, as well as timing and type of intervention. RECENT FINDINGS: Females present with more complicated disease: anterior or bileaflet prolapse, leaflet dysplasia/thickening, mitral annular calcification, and mixed mitral lesions. The absence of indexed echocardiographic mitral regurgitation (MR) severity parameters contributes to delayed intervention in women, resulting in more severe symptom burden at time of surgery. The sequelae of chronic MR also necessitate concomitant procedures (e.g. tricuspid repair, arrhythmia surgery) at the time of mitral surgery. Complex MV pathology, greater patient acuity, and more complicated procedures collectively pose challenges to successful MV repair and postoperative recovery. As a consequence, women receive disproportionately more MV replacement than men. In-hospital mortality after MV repair is also greater in women than men. Long-term outcomes of MV repair are comparable after risk-adjustment for preoperative status; however, women experience a greater incidence of postoperative heart failure. SUMMARY: To address the inequity in MV repair outcomes between sexes, indexed diagnostic measurements, diligent surveillance of asymptomatic MR, increased recruitment of women in large clinical trials, and mandatory reporting of sex-based subgroup analyses are recommended.

Days alive and out of hospital for adult female and male cardiac surgery patients: a population-based cohort study.

BACKGROUND: Research shows women experience higher mortality than men after cardiac surgery but information on sex-differences during postoperative recovery is limited. Days alive and out of hospital (DAH) combines death, readmission and length of stay, and may better quantify sex-differences during recovery. This main objective is to evaluate (i) how DAH at 30-days varies between sex and surgical procedure, (ii) DAH responsiveness to patient and surgical complexity, and (iii) longer-term prognostic value of DAH. METHODS: We evaluated 111,430 patients (26% female) who underwent one of three types of cardiac surgery (isolated coronary artery bypass [CABG], isolated non-CABG, combination procedures) between 2009 - 2019. Primary outcome was DAH at 30 days (DAH30), secondary outcomes were DAH at 90 days (DAH90) and 180 days (DAH180). Data were stratified by sex and surgical group. Unadjusted and risk-adjusted analyses were conducted to determine the association of DAH with patient-, surgery-, and hospital-level characteristics. Patients were divided into two groups (below and above the 10th percentile) based on the number of days at DAH30. Proportion of patients below the 10th percentile at DAH30 that remained in this group at DAH90 and DAH180 were determined. RESULTS: DAH30 were lower for women compared to men (22 vs. 23 days), and seen across all surgical groups (isolated CABG 23 vs. 24, isolated non-CABG 22 vs. 23, combined surgeries 19 vs. 21 days). Clinical risk factors including multimorbidity, socioeconomic status and surgical complexity were associated with lower DAH30 values, but women showed lower values of DAH30 compared to men for many factors. Among patients in the lowest 10th percentile at DAH30, 80% of both females and males remained in the lowest 10th percentile at 90 days, while 72% of females and 76% males remained in that percentile at 180 days. CONCLUSION: DAH is a responsive outcome to differences in patient and surgical risk factors. Further research is needed to identify new care pathways to reduce disparities in outcomes between male and female patients.

Changes in Cardiac Function During a Swallow Exercise Program in Patients with Coronary Artery Disease.

Research regarding risks of swallow treatment suggests that patients with coronary artery disease (CAD) experience changes in heart rate/rhythm when completing the supraglottic swallow and super-supraglottic swallow. The current study evaluated cardiac function during multiple swallowing exercises in patients with dysphagia and CAD. Eligible patients had CAD and confirmed pharyngeal dysphagia from VFS and sufficient cognitive ability to follow direction. The protocol included an a priori concealed randomized order of seven swallowing exercises (supraglottic swallow, super-supraglottic swallow, Mendelsohn and Masako maneuvers, effortful swallow with and without breath hold, and jaw opening exercise). Objective measures of heart rate/rhythm, oxygen saturation, and blood pressure were compared before vs after the overall session and each exercise using the Wilcoxon signed-rank test, and McNemar's and Cochran's Q tests with alpha at 0.05 and power at 0.80. Participants were 20 adults (15 male), aged 28-88 (median 76.5 years). 90% were intubated during their hospital stay (44% > 1 intubation) and 20% suffered post-op stroke. Severe dysphagia, marked by NPO status, occurred in 30% of patients. Sessions were 26 min long (mean; SD = 2.29). With few exceptions, objective measures were stable pre vs post overall and after each exercise. Potential vulnerability was noted with increased heart rate after the super-supraglottic swallow and increased arrhythmias after the effortful swallow (p < 0.05 for both). The order that swallowing exercises were completed did not significantly impact cardiovascular function. Telemetry and pulse oximetry proved to be feasible tools to monitor for subtle changes in cardiovascular function during completion of swallowing exercises.

Stuck between a rock and a hard place: The clinical conundrum of managing cardiac surgical patients during the SARS-CoV-2 pandemic.

Deferring nonemergent cardiac surgery became the strategy of choice for several international healthcare systems afflicted by high case burdens of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) to both conserve valuable healthcare resources and protect patients from possible exposure. Missing from the available dataset to help guide policy development has been a clear understanding of the extent to which COVID-19 infection modulates cardiac surgery outcomes. In their investigation, Bonalumi et al. uncovered an inpatient COVID-19 positivity rate of almost 10 times higher than that of the general Italian population, as well as a mortality rate over 20 times higher amongst cardiac surgery patients with perioperative COVID-19 infection compared to those COVID-negative. While the summation of available evidence points to the serious consideration cardiac surgeons must give to delaying surgeries during the COVID-19 pandemic, recognition must be given to the risks that postponing cardiac surgery may have on patient outcomes. Emerging data is beginning to demonstrate the efficacy of vaccination in preventing postoperative COVID-19 infection and morbidity.

Outcomes of expanded polytetrafluoroethylene pericardial membrane implantation in left ventricular assist device explantation and heart transplantation.

OBJECTIVES: Redo sternotomy and explantation of left ventricular assist devices (LVAD) for heart transplantation (HT) involve prolonged dissection, potential injury to mediastinal structures and/or bleeding. Our study compared a complete expanded polytetrafluoroethylene (ePTFE) wrap versus minimal or no ePTFE during LVAD implantation, on outcomes of subsequent HT. METHODS: Between July 2005 and July 2018, 84 patients underwent a LVAD implant and later underwent HT. Thirty patients received a complete ePTFE wrap during LVAD implantation (Group 1), and 54 patients received either a sheet of ePTFE placed in the anterior mediastinum or no ePTFE (Group 2). RESULTS: Baseline characteristics were similar between Groups 1 and 2. Surgeons reported subjective improvements in speed, predictability, and safety of dissection with complete ePTFE compared with minimal or no ePTFE. Time from incision to initiation of cardiopulmonary bypass (CPB) were similar between groups (97 ± 38 vs. 89 ± 29 min, p = .3). Injury to mediastinal structures during the dissection was similar between groups (10% vs. 11%, p > .9). While surgeons reported less intraoperative bleeding in Group 1 (43% vs. 61%), this trend did not reach significance (p = .1). In-hospital mortality, intensive care unit length of stay and hospital length of stay were similar between both groups. CONCLUSIONS: In patients undergoing LVAD explant-HT, there was a trend toward reduced surgeon reported intraoperative bleeding with ePTFE placement. Despite qualitatively reported greater ease and speed of mediastinal dissection with ePTFE membrane placement, time to initiation of CPB did not differ, likely because surgeons remained cautious, allowing extra time for unanticipated difficulties.

Ticagrelor use and practice patterns among Canadian cardiac surgeons.

BACKGROUND AND AIM: The P2Y12 platelet receptor inhibitor ticagrelor is widely used in patients following acute coronary syndromes or in those who have received coronary stents. Bentracimab is a monoclonal antibody-based reversal agent that is being formally evaluated in a Phase 3 clinical trial. Here, we probe the knowledge, attitudes, and practice patterns of cardiac surgeons regarding their perioperative management of ticagrelor and potential application of a ticagrelor reversal agent. METHODS: A questionnaire was developed by a working group of cardiac surgeons to inquire into participants' practices and beliefs regarding ticagrelor and disseminated to practicing, Canadian-trained cardiac surgeons. RESULTS: A total of 70 Canadian-trained cardiac surgeons participated. Bleeding risk was identified as the most significant consideration when surgically revascularizing ticagrelor-treated patients (90%). There is variability in the duration of withholding ticagrelor before coronary artery bypass graft procedure in a stable patient; 44.3% wait 3 days and 32.9% wait 4 days or longer. Currently, 15.7% of cardiac surgeons prophylactically give platelet transfusions and fresh frozen plasma intraoperatively following protamine infusion in patients who have recently received ticagrelor. Interestingly, 47.1% of surveyed surgeons were aware of a reversal agent for ticagrelor, 91.4% of cardiac surgeons would consider utilizing a ticagrelor reversal agent if available, and 51.4% acknowledged that the introduction of such an agent would be a major advance in clinical practice. CONCLUSIONS: The present survey identified ticagrelor-related bleeding as a major concern for cardiac surgeons. Surgeons recognized the significant unmet need that a ticagrelor reversal agent would address.

Predictors of hospital mortality after surgery for ischemic mitral regurgitation: the Toronto General Hospital experience.

BACKGROUND: The benefit of mitral valve repair (MVr) over replacement in patients with severe ischemic mitral regurgitation (IMR) is still controversial. We report our early postoperative outcomes of repair versus replacement. METHODS: Data were collected for patients undergoing first-time mitral valve surgery for severe IMR between 1990 and 2009 (n = 393). Patients who underwent combined procedures for papillary muscle rupture, post-infarction ventricular septal defect, endocarditis, or any previous cardiac surgery were excluded. Preoperative demographics, operative variables, and hospital outcomes were analyzed, and multivariable regression analysis was employed to identify independent predictors of hospital mortality. RESULTS: Valve repair was performed in 42% (n = 164) of patients and replacement in 58% (n = 229). Patients who underwent replacement were older and had a higher prevalence of unstable angina, New York Heart Association Class IV symptoms, preoperative cardiogenic shock, preoperative myocardial infarction, peripheral vascular disease, renal failure, and urgent or emergency surgery (all p < .05). Unadjusted hospital mortality was higher in patients undergoing valve replacement (13% vs. 5%; p = .01). Valve repair was associated with a lower prevalence of postoperative low cardiac output syndrome. Multivariable analysis revealed that age, urgency of operation, and preoperative left ventricular (LV) function were independent predictors of hospital mortality. Importantly, MVr versus replacement was not an independent predictor of hospital mortality. CONCLUSION: Our data did not suggest an early survival benefit to MVr over replacement for IMR. However, age, LV dysfunction, and the need for urgent surgery were independently associated with hospital mortality.

Knockout of Canopy 2 activates p16INK4a pathway to impair cardiac repair.

BACKGROUND: Cardiac repair depends on angiogenesis and cell proliferation. Previously we identified Canopy 2 (CNPY2) as a secreted angiogenic growth factor which promotes neovascularization. We investigated the role of CNPY2 in cardiac repair following myocardial infarction (MI) and the possible mediators involved using Cnpy2 knockout (KO) mice and human cardiac tissue. METHODS AND RESULTS: Cardiac tissue from patients with end-stage heart failure had significantly lower endogenous CNPY2 expression compared to samples from control patients. CNPY2 expression in mouse hearts significantly decreased following MI. Significantly less leukocyte and endothelial cell proliferation was found in Cnpy2 KO than wild-type (WT) mice post MI which contributed to impaired angiogenesis, tissue repair, and decreased cardiac function (fractional shortening: WT: 21.1 ±â€¯2.1% vs. KO: 16.4 ±â€¯1.6%, p < .01 at day 28 post MI). RT-qPCR revealed significantly increased p16INK4a expression in Cnpy2 KO mouse hearts (WT: 1.0 ±â€¯0.04 vs. KO: 2.33 ±â€¯0.11 [relative expression of p16 INK4a], p < .01) which was confirmed by immunostaining (WT: 8.47 ±â€¯1.22 vs. KO: 12.9 ±â€¯1.22 [% total cells], p < .05) for the p16INK4a protein. Expression of cell cycle-related proteins, cyclin D1, cyclin-dependent kinases 4 and 6, and phosphorylated retinoblastoma protein (pRb) was significantly decreased in Cnpy2 KO mouse hearts. The up-regulation of the p16INK4a/cyclin D1/Rb pathway by knockout of Cnpy2 was accompanied by attenuation of PDK1/Akt phosphorylation. MI exacerbated the detrimental effects of p16INK4a on tissue repair in Cnpy2 KO mice. Overexpression of CNPY2 in the cardiac tissue of transgenic mice reversed the inhibition of cell proliferation through suppression of the p16INK4a pathway. CONCLUSIONS: Cardiac injury and progressive heart failure were associated with decreased CNPY2 levels in both humans and mice. Knockout of Cnpy2 resulted in up-regulation of p16INK4a which impaired cardiac function and tissue repair. These data suggest that CNPY2 is an important regulator of p16INK4a and promotes cell proliferation and tissue repair through inhibition of the p16INK4a pathway. CNPY2 treatment may offer a new approach to restore cardiac function after an MI.

Novel mediators of aneurysm progression in bicuspid aortic valve disease.

Bicuspid aortic valve (BAV) disease is a congenital abnormality that is associated with ascending aortic aneurysm yet many of the molecular mechanisms remain unknown. To identify novel molecular mechanisms of aneurysm formation we completed microarray analysis of the proximal (severely dilated) and distal (less dilated) regions of the ascending aorta from five patients with BAV. We identified 180 differentially expressed genes, 40 of which were validated by RT-qPCR. Most genes had roles in inflammation and endothelial cell function including cytokines and growth factors, cell surface receptors and the Activator Protein 1 (AP-1) transcription factor family (FOS, FOSB and JUN) which was chosen for further study. AP-1 was differentially expressed within paired BAV aneurysmal samples (n = 8) but not Marfan patients (n = 5). FOS protein was significantly enriched in BAV aortas compared to normal aortas but unexpectedly, ERK1/2 activity, an upstream regulator of FOS was reduced. ERK1/2 activity was restored when BAV smooth muscle cells were cultured in vitro. An mRNA-miRNA network within paired patient samples identified AP-1 as a central hub of miRNA regulation. FOS knockdown in BAV SMCs increased expression of miR-27a, a stretch responsive miRNA. AP-1 and miR-27a were also dysregulated in a mouse model of aortic constriction. In summary, this study identified a central role for AP-1 signaling in BAV aortic dilatation by using paired mRNA-miRNA patient sample. Upstream analysis of AP-1 regulation showed that the ERK1/2 signaling pathway is dysregulated and thus represents a novel chain of mediators of aortic dilatation in BAV which should be considered in future studies.

Surgical Enlargement of the Aortic Root Does Not Increase the Operative Risk of Aortic Valve Replacement.

BACKGROUND: Surgical aortic root enlargement (ARE) during aortic valve replacement (AVR) allows for larger prosthesis implantation and may be an important adjunct to surgical AVR in the transcatheter valve-in-valve era. The incremental operative risk of adding ARE to AVR has not been established. We aimed to evaluate the early outcomes of patients undergoing AVR with or without ARE. METHODS: From January 1990 to August 2014, 7039 patients underwent AVR (AVR+ARE, n=1854; AVR, n=5185) at a single institution. Patients with aortic dissection and active endocarditis were excluded. Mean age was 65±14 years and 63% were male. Logistic regression and propensity score matching were used to adjust for unbalanced variables in group comparisons. RESULTS: Patients undergoing AVR+ARE were more likely to be female (46% versus 34%, P<0.001) and had higher rates of previous cardiac surgery (18% versus 12%, P<0.001), chronic obstructive pulmonary disease (5% versus 3%, P=0.004), urgent/emergent status (6% versus 4%, P=0.01), and worse New York Heart Association status (P<0.001). Most patients received bioprosthetic valves (AVR+ARE: 73.4% versus AVR: 73.3%, P=0.98) and also underwent concomitant cardiac procedures (AVR+ARE: 68% versus AVR: 67%, P=0.31). Mean prosthesis size implanted was slightly smaller in patients requiring AVR+ARE versus AVR (23.4±2.1 versus 24.1±2.3, P<0.001). In-hospital mortality was higher after AVR+ARE (4.3% versus 3.0%, P=0.008), although when the cohort was restricted to patients undergoing isolated aortic valve replacement with or without root enlargement, mortality was not statistically different (AVR+ARE: 1.7% versus AVR: 1.1%, P=0.29). After adjustment for baseline characteristics, AVR+ARE was not associated with an increased risk of in-hospital mortality when compared with AVR (odds ratio, 1.03; 95% confidence interval, 0.75-1.41; P=0.85). Furthermore, AVR+ARE was not associated with an increased risk of postoperative adverse events. Results were similar if propensity matching was used instead of multivariable adjustments for baseline characteristics. CONCLUSIONS: In the largest analysis to date, ARE was not associated with increased risk of mortality or adverse events. Surgical ARE is a safe adjunct to AVR in the modern era.

Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial.

Importance: Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery. Objective: To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant. Design, Setting, and Participants: A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018. Interventions: Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n = 106 vs n = 53). Main Outcomes and Measures: The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival. Results: Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P = .55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P = .80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P = .63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P = .68). Conclusions and Relevance: Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support. Trial Registration: clinicaltrials.gov Identifier: NCT02362646.

Practical valvular issues in patients requiring ventricular assist devices.

PURPOSE OF REVIEW: As ventricular assist device (VAD) therapy in patients with advanced heart failure continues to grow, experience with concomitant valvular diseases present either before or after VAD implantation continues to accrue. In this review, we discuss recent data and current practice as it pertains to the subject of concomitant valvular disease in patients requiring VADs. RECENT FINDINGS: Persistent aortic valve closure has been identified as a potential contributor to aortic valve 'disuse atrophy' resulting in valve degeneration. Dilation of the aortic root may be predictive of future development of aortic insufficiency. Novel echocardiographic parameters to identify the severity of aortic insufficiency following VAD implantation may be useful for risk stratification. Concomitant repair of significant mitral regurgitation may confer benefit to pulmonary vascular resistance and right ventricular function; however, this remains controversial. Concomitant repair of significant tricuspid regurgitation has not demonstrated early postoperative benefit nor survival benefit. Atrial fibrillation has emerged as a risk factor that may predict accelerated progression of postoperative tricuspid regurgitation. SUMMARY: Management of aortic insufficiency, mitral regurgitation or tricuspid regurgitation in patients requiring VADs continues to be the source of controversy. As experience accrues with varying strategies to prevent or manage these valvular lesions, our understanding of the impact of these strategies continues to evolve.

Early pneumopericardium after heart transplantation.

A 60-year-old woman with a history of dilated cardiomyopathy underwent heart transplantation. One month post discharge, she presented to clinic with low-grade fever and productive cough. Her chest radiograph showed air-fluid levels in the pericardial silhouette. Transthoracic echocardiogram showed a large complex pericardial collection with no evidence of cardiac tamponade. The patient was urgently taken to the operating room for exploration. A large "egg-shaped" mass in the pericardium measuring 10 × 12 cm with gaseous material was aspirated. As the posterior wall of the mass was firmly adhered to the right atrium, the capsule was incompletely excised. We present the case of a potentially life-threatening complication post transplantation that required surgical debridement and life-long antibiotic suppressive therapy. To our knowledge, this is the first report of purulent pericardial collection caused by Enterobacter cancerogenous. Further research is required to better understand the biology of this microorganism and the role it may play as a pathogen in immunocompromised patients following solid organ transplantation.

Tranexamic Acid Dosing for Cardiac Surgical Patients With Chronic Renal Dysfunction: A New Dosing Regimen.

BACKGROUND: Tranexamic acid (TXA) is a common antifibrinolytic agent used to minimize bleeding in cardiac surgery. Up to 50% cardiac surgical patients have chronic renal dysfunction (CRD). Optimal dosing of TXA in CRD remains poorly investigated. This is important as TXA is renally eliminated with accumulation in CRD. High TXA doses are associated with postoperative seizures. This study measures plasma TXA concentrations in CRD cardiac surgical patients for pharmacokinetic modeling and dose adjustment recommendations. METHODS: This prospective cohort study enrolled 48 patients with stages 1-5 CRD, classified by Kidney Disease Outcome Quality Initiative. Patients were separated into 2 treatment groups. A "low-risk" group underwent simple aortocoronary bypass or single-valve repair/replacement and received a 50 mg/kg TXA bolus. A "high-risk" group underwent redo, aortic, multiple valve or combination surgery and received the Blood Conservation Using Anti-fibrinolytics Trial dosing regimen (loading dose 30 mg/kg, infusion 16 mg/kg/h with 2 mg/kg in pump prime). Primary outcome identified changes in TXA clearance and distribution volume, which provided the rationale for dose adjustment. Descriptive clinical outcomes assessed postoperative seizures, blood loss, ischemic-thrombotic complications, in-hospital mortality, and length of hospital stay. RESULTS: TXA concentrations were elevated and sustained above the therapeutic threshold for approximately 12 hours in high-risk stages 3-5 groups, in accordance to CRD severity. CONCLUSIONS: Using a pharmacokinetic model, we propose a simple new TXA dosing regimen that optimizes maximal antifibrinolysis and avoids excessive drug dosing.

Skin-derived precursors from human subjects with Type 2 diabetes yield dysfunctional vascular smooth muscle cells.

Objective: Few methods enable molecular and cellular studies of vascular aging or Type 2 diabetes (T2D). Here, we report a new approach to studying human vascular smooth muscle cell (VSMC) pathophysiology by examining VSMCs differentiated from progenitors found in skin. Approach and results: Skin-derived precursors (SKPs) were cultured from biopsies (N=164, ∼1 cm2) taken from the edges of surgical incisions of older adults (N=158; males 72%; mean age 62.7 ± 13 years) undergoing cardiothoracic surgery, and differentiated into VSMCs at high efficiency (>80% yield). The number of SKPs isolated from subjects with T2D was ∼50% lower than those without T2D (cells/g: 0.18 ± 0.03, N=58 versus 0.40 ± 0.05, N=100, P<0.05). Importantly, SKP-derived VSMCs from subjects with T2D had higher Fluo-5F-determined baseline cytosolic Ca2+ concentrations (AU: 1,968 ± 160, N=7 versus 1,386 ± 170, N=13, P<0.05), and a trend toward greater Ca2+ cycling responses to norepinephrine (NE) (AUC: 177,207 ± 24,669, N=7 versus 101,537 ± 15,881, N=20, P<0.08) despite a reduced frequency of Ca2+ cycling (events s-1 cell-1: 0.011 ± 0.004, N=8 versus 0.021 ± 0.003, N=19, P<0.05) than those without T2D. SKP-derived VSMCs from subjects with T2D also manifest enhanced sensitivity to phenylephrine (PE) in an impedance-based assay (EC50 nM: 72.3 ± 63.6, N=5 versus 3,684 ± 3,122, N=9, P<0.05), and impaired wound closure in vitro (% closure: 21.9 ± 3.6, N=4 versus 67.0 ± 10.3, N=4, P<0.05). Compared with aortic- and saphenous vein-derived primary VSMCs, SKP-derived VSMCs are functionally distinct, but mirror defects of T2D also exhibited by primary VSMCs. CONCLUSION: Skin biopsies from older adults yield sufficient SKPs to differentiate VSMCs, which reveal abnormal phenotypes of T2D that survive differentiation and persist even after long-term normoglycemic culture.

Left ventricular assist device exchange: the Toronto General Hospital experience.

BACKGROUND: As support times for left ventricular assist devices (LVADs) become longer, several complications requiring device exchange may occur. To our knowledge, this is the first Canadian report regarding implantable LVAD exchange. METHODS: We retrospectively reviewed the cases of consecutive, unique patients implanted with an LVAD between June 2006 and October 2015 at Toronto General Hospital. RESULTS: In total, 122 patients were impanted with an LVAD during the study period. Eight patients required LVAD exchange, and 1 patient had 2 replacements (9 of 122, 7.3%). There were 7 HeartMate II (HMII), 1 HVAD and 1 DuraHeart pumps exchanged. Two of these exchanges occurred early at the time of initial implant, whereas 7 occurred late (range 8-623 d). Six exchanges were made owing to pump thrombosis. Of the 3 exchanges made for other causes, 1 HMII exchange was owing to a driveline fracture, 1 DuraHeart patient had early inflow obstruction requiring exchange to HMII at the initial implant, and the third had a suspected inflow obstruction with no evidence of thrombosis at the time of the procedure. The mean support time before exchange was 225 days, and time from exchange to transplant, death or ongoing support was 245 days. Three patients were successfully bridged to transplant, and at the time of data collection 2 were supported awaiting transplant. Three patients died after a mean duration of 394.3 days (range 78-673 d) of support postreplacement. Four cases were successfully performed using a subcostal approach. CONCLUSION: Pump thrombosis is the most common cause for LVAD exchange, which can be performed with acceptable morbidity and mortality. The subcostal approach may be the preferred procedure for an HMII exchange when indicated.

CONTEXTE: À mesure que la durée d'utilisation des dispositifs d'assistance ventriculaire gauche (DAVG) augmente, plusieurs complications nécessitant un remplacement du dispositif peuvent survenir. À notre connaissance, il s'agit du premier rapport canadien concernant le remplacement des DAVG implantables. MÉTHODES: Nous avons passé en revue de manière rétrospective les cas individuels consécutifs de patients à qui on a implanté un DAVG entre juin 2006 et octobre 2015 à l'Hôpital Général de Toronto. RÉSULTATS: En tout, 122 patients ont reçu un DAVG pendant la période de l'étude. Huit patients ont eu besoin d'un remplacement de DAVG et 1 patient a eu besoin de 2 remplacements (9 sur 122, 7,3 %). Sept dispositifs HeartMate II (HMII), 1 dispositif HVAD et 1 dispositif DuraHeart ont été remplacés. Deux de ces remplacements sont survenus peu de temps après la pose initiale du dispositif, tandis que les 7 autres se sont produits plus tardivement (dans les 8 à 623 jours suivants). Six remplacements ont été effectués en raison d'une thrombose de la pompe. Parmi les 3 remplacements effectués pour d'autres raisons, 1 dispositif HMII a été remplacé en raison d'un bris de la ligne d'activation, 1 dispositif DuraHeart a présenté une obstruction précoce du flux entrant nécessitant la pose d'un HMII dès l'implantation initiale, et le troisième présentait une obstruction présumée du flux entrant sans signe de thrombose au moment de l'intervention. La durée moyenne d'utilisation avant le remplacement du dispositif a été de 225 jours, et l'intervalle entre le remplacement et la transplantation, le décès ou la décision de maintenir l'assistance a été de 245 jours. L'appareil a permis une transition réussie jusqu'à la transplantation chez 3 patients, et au moment de la collecte des données, 2 patients porteurs d'un DAVG étaient en attente d'une transplantation. Trois patients sont décédés après une durée moyenne de 394,3 jours (entre 78 et 673 jours) d'assistance post-remplacement. Quatre remplacements ont été effectués avec succès par une approche sous-costale. CONCLUSION: La thrombose de la pompe est la cause la plus fréquente de remplacement d'un DAVG; le remplacement peut être effectué avec des taux de morbidité et de mortalité acceptables. L'approche sous-costale serait à privilégier lorsqu'un remplacement de HMII est indiqué.

Tricuspid Valve Annular Dilation as a Predictor of Right Ventricular Failure After Implantation of a Left Ventricular Assist Device.

BACKGROUND: Tricuspid annular (TA) dilation has been suggested as a more reliable marker of concomitant advanced right ventricular failure (RVF) than severity of tricuspid regurgitation (TR). Our objective was to examine the impact of TA dilation on occurrence of RVF and in-hospital mortality following left ventricular assist device (LVAD) implant. METHODS: Consecutive patients undergoing implantation of a continuous-flow LVAD implant were grouped according to the presence or absence of preoperative dilated TA. Clinical characteristics, hemodynamics, and short-term postoperative outcomes were compared between groups. RVF was defined as unplanned right ventricular assist device (RVAD) or postoperative use of inotropes for >14 days. Linear and logistic regressions were used to explore associations of TA with occurrence of RVF and duration of inotrope use. RESULTS: We included 69 patients who had continuous-flow LVAD implanted between 2006 and 2013 (50 ± 13 years old; 69% males; 37% ischemic etiology; 69% bridge-to-transplant LVAD; 18% INTERMACS 1-2; 48% with significant TR). RVF occurred in nine cases, and overall in-hospital mortality rate was 14%. Tricuspid valve repair was performed in ten cases. Dilated TA (OR 4.86; 95% CI 1.05-22.33; p = 0.04) was associated with RVF. In an adjusted multivariable analysis, indexed TA was an independent predictor of increased days of inotrope use (0.8-day increase in inotrope use for every 1 mm/m2 increase; p = 0.04). CONCLUSION: In this cohort, TA dilation was a predictor of RVF after LVAD implant. The potential benefit of concomitant TVR in selected patients with a dilated TA undergoing LVAD implantation remains to be determined.

Facilitators and Barriers of Heart Surgery Discharge: Patients' and Nurses' Narrative Accounts.

BACKGROUND: Optimal patient recovery from open-heart surgery relies on effective discharge planning and education. However, the nature of the discharge experience has not been clearly described. OBJECTIVE: The study purpose is to explore patients' and nurses' narrative accounts of the facilitators and barriers of heart surgery discharge. METHODS: A qualitative study was employed using a narrative methodology that elicited and analyzed stories. This research was conducted in a large, urban hospital in Ontario, Canada. A total of 17 patients and nurses were recruited. Five female and 5 male patients were recruited from a preoperative clinic. Ages ranged from 37 to 80 years. Seven nurses were recruited from inpatient cardiovascular units. They had 2 to 19 years of cardiovascular nursing experience. Semistructured, narrative-based interviews were conducted. Two interviews were conducted with each patient at 1 week after discharge and at 4 to 6 weeks. One interview was conducted with each nurse. RESULTS: Findings indicate that although the preoperative period was identified as an effective time for discharge preparation, the patient's cognitive capacity was limited during the postoperative phase of surgery. Both nurses and patients also found that insufficient time impeded the discharge process and limited individualized discussions. The structured and standardized delivery of discharge information affected patients' capacity to apply it to the particularities in their own lives and homes. The fostering of therapeutic relationships created a space where patients felt comfortable sharing their concerns and nurses learned more about patients and thus could better tailor the discharge approach. CONCLUSIONS: Study recommendations include group and scenario-based education in which patients and nurses brainstorm about how to apply the discharge information to the particularities of patients' lives and homes. Provision of support needs to be bolstered during the home period, where patients have timely opportunities to discuss their concerns and questions with practitioners or possibly peers.

Volatile-based short-term sedation in cardiac surgical patients: a prospective randomized controlled trial.

OBJECTIVE: To evaluate the differences in extubation times in a group of cardiac surgical patients who were anesthetized and sedated with either IV propofol or inhaled volatile anesthetic agents. DESIGN: This was a prospective randomized controlled trial performed between September 2009 and August 2011. SETTING: Cardiovascular ICU within a tertiary referral university-affiliated teaching hospital. PATIENTS: One hundred forty-one patients undergoing coronary artery bypass graft surgery with normal or mildly reduced left ventricular systolic function. INTERVENTION: Participants were randomly assigned to receive anesthesia and postoperative sedation using IV propofol (n = 74) or inhaled volatile (isoflurane or sevoflurane) anesthetic agent (n = 67). MEASUREMENTS AND MAIN RESULTS: Patients sedated using inhaled volatile agent displayed faster readiness to extubation time at 135 minutes (95-200 min) compared with those receiving IV propofol at 215 minutes (150-280 min) (p < 0.001). Extubation times were faster within the volatile group at 182 minutes (140-255 min) in comparison with propofol group at 291 minutes (210-420 min) (p < 0.001). The volatile group showed a higher prevalence of vasodilatation with hypotension and higher cardiac outputs necessitating greater use of vasoconstrictors. There was no difference in postoperative pain scores, opioid consumption, sedation score, ICU or hospital length of stay, or patient mortality. CONCLUSIONS: Inhaled volatile anesthesia and sedation facilitates faster extubation times in comparison with IV propofol for patient undergoing coronary artery bypass graft surgery.