Alan H. Menkis

Porcine bioprosthetic heart valves: The next generation

There have been significant advances in organ xenotransplantation (cross-species transplantation), especially in the development of genetically engineered pigs, but clinical trials of solid organ transplants are still a time away. However, there is a form of pig-to-human xenotransplantation that has been taking place since the 1960s-bioprosthetic heart valve (BHV) replacement. Recently, there has been increasing evidence that, despite glutaraldehyde fixation of BHVs, there is a significant immune reaction to the valves, leading to calcification, rapid structural deterioration, and failure, particularly in young patients who have a more vigorous immune system and metabolism than the elderly. However, it is the young patients who would most benefit from such BHVs because these avoid the complications associated with the lifelong anticoagulation required with mechanical valves. In this review, we examine pathologic and immunohistochemical reports of failed BHVs that suggest that there is an immune response to these valves. Small animal studies that link the development of calcification and BHV failure to the immune response are reviewed. We draw parallels between the problems of glutaraldehyde-fixed tissue xenotransplantation and those currently being faced in live organ xenotransplantation. Finally, we discuss the advances being made in the production of genetically modified pigs and the evidence that these pigs may become a source of BHVs that can be used worldwide to treat valvular heart disease in children and young adults (for whom there is no ideal valve replacement in existence today). The design of a BHV that is resistant to the hosts immune response would be a major step forward in cardiac surgery.

Bioprosthetic heart valves of the future

Glutaraldehyde‐fixed bioprosthetic heart valves (GBHVs), derived from pigs or cows, undergo structural valve deterioration (SVD) over time, with calcification and eventual failure. It is generally accepted that SVD is due to chemical processes between glutaraldehyde and free calcium ions in the blood. Valve companies have made significant progress in decreasing SVD from calcification through various valve chemical treatments. However, there are still groups of patients (e.g., children and young adults) that have accelerated SVD of GBHV. Unfortunately, these patients are not ideal patients for valve replacement with mechanical heart valve prostheses as they are at high long‐term risk from complications of the mandatory anticoagulation that is required. Thus, there is no “ideal” heart valve replacement for children and young adults. GBHVs represent a form of xenotransplantation, and there is increasing evidence that SVD seen in these valves is at least in part associated with xenograft rejection. We review the evidence that suggests that xenograft rejection of GBHVs is occurring, and that calcification of the valve may be related to this rejection. Furthermore, we review recent research into the transplantation of live porcine organs in non‐human primates that may be applicable to GBHVs and consider the potential use of genetically modified pigs as sources of bioprosthetic heart valves.

Long-Term Angiographic Follow-Up of Robotic-Assisted Coronary Artery Revascularization

BACKGROUND Robotic-assisted coronary artery bypass grafting (CABG) has been shown in short-term studies to increase patient satisfaction and to reduce surgical morbidity and recovery times. However, the long-term patency rate of robotic-assisted CABG is unknown. Therefore, the objective of this study was to assess the long-term patency rate of robotic-assisted coronary artery bypass grafts. METHODS The study cohort included all patients who underwent robotic-assisted conduit dissection for CABG at London Health Sciences Centre between September 1999 and December 2003. These patients had selective graft patency assessment using cardiac catheterization or computed tomography angiography (CTA), or both, and stress myocardial perfusion scintigraphy (MPS) 5 to 10 years after surgery to evaluate graft patency and to give functional information on the hemodynamic significance of any graft stenosis. Patients also completed quality of life questionnaires. RESULTS From a total of 160 patients who underwent robotic-assisted CABG, 82 eligible patients were followed with graft patency assessments for a mean period of 8 years±16.3 months. The patency rate of all robotic-assisted CABG grafts in this patient cohort was 92.7%. The patency rate of left internal thoracic artery grafts to the left anterior descending artery after robotic-assisted CABG in this patient cohort was 93.4%. Patients consistently attained high scores on quality of life questionnaires after surgery. CONCLUSIONS The long-term patency rate of grafts after robotic-assisted CABG was 92.7% at a mean follow-up period of 95.8±16.3 months. Specifically, the patency rate of left internal thoracic artery grafts to the left anterior descending artery after robotic-assisted CABG was 93.4%.

Minimally invasive left-heart decompression during venoarterial extracorporeal membrane oxygenation: an alternative to a percutaneous approach.

Decompression of the left-heart following initiation of extracorporeal membrane oxygenation, is at times required. In the setting of a closed chest this can present a challenge. We present a minimally invasive approach to left-heart decompression in an adult-sized patient, where a percutaneous option was not feasible.

Cost–effectiveness analysis of rheumatic heart disease prevention strategies

Rheumatic heart disease (RHD), secondary to group A streptococcal infection is endemic in the developing as well as parts of the developed world with significant costs to the patient, and to the healthcare system. We briefly review the prevalence and cost of RHD in developed and developing nations. We subsequently develop a Markov model to evaluate the cost-effectiveness of three strategies (vs standard no prevention) for preventing RHD in a developing world country: primary prophylaxis (throat swab to detect and subsequently treat group A streptococci as needed); primary prophylaxis (antibiotic prophylaxis for all) with benzathine penicillin G once monthly to all patients (ages 5–21 years) regardless of evidence of infection; and secondary prophylaxis with monthly only to those with echocardiographic evidence of early RHD. Our model suggests that echocardiographic screening and secondary prophylaxis is the best strategy although the strategies change depending on parameters used.

Predictors of survival, functional survival, and hospital readmission in octogenarians after surgical aortic valve replacement

Objective: To analyze outcomes and predictors of functional survival (personal care home admission and mortality) and hospital readmission in patients aged ≥80 years who underwent surgical aortic valve replacement (SAVR) in a Manitoba hospital. Methods: This was a retrospective cohort study of patients aged ≥80 years who underwent SAVR with or without coronary artery bypass grafting in Manitoba between 1995 and 2014. Data from the Manitoba Adult Cardiac Surgery database and the Manitoba Centre for Health Policy were used. Kaplan–Meier estimates of outcomes and Cox multivariate regression analysis of risk factors were performed. Survival was compared with that of age‐ and sex‐matched life expectancy. Results: A total of 1872 patients were aged ≥50 years and 378 were aged ≥80 years, 55% of whom (n = 208) underwent concurrent coronary artery bypass grafting. Compared with younger patients, octogenarians had higher in‐hospital mortality (8.5%; P <.001), longer median intensive care unit stay (47.2 hours; P <.001), and longer median in‐hospital stay (13 days; P <.001). The median follow‐up was 5.2 years. Functional survival was 82.4% at 1 year and 56.5% at 5 years, and freedom from hospital readmission was 61.5% at 1 year and 28.4% at 5 years. Survival approximated the age‐ and sex‐matched life expectancy at 1 year (83.8%) and 5 years (60.8%). Preoperative atrial fibrillation, peripheral vascular disease, female sex, postoperative acute kidney injury, and blood transfusion were associated with adverse outcomes. Conclusions: In eligible octogenarians, SAVR has acceptable 1‐ and 5‐year functional survival and hospital readmission rates, but significant perioperative mortality and morbidity.

Early Rehospitalization After Prolonged Intensive Care Unit Stay Post Cardiac Surgery: Outcomes and Modifiable Risk Factors

Background Prolonged intensive care unit length of stay (prICULOS) following cardiac surgery (CS) in older adults is increasingly common but rehospitalization characteristics and outcomes are understudied. We sought to describe the rehospitalization characteristics and subsequent non‐institutionalized survival of prICULOS (ICULOS ≥5 days) patients and identify modifiable risk factors to decrease 30‐day rehospitalization. Methods and Results Consecutive patients from January 1, 2000 to December 31, 2011 were analyzed utilizing linked clinical and administrative databases. Logistic regression was used to identify risk factors associated with 30‐day rehospitalization. Out of 9210 consecutive patients discharged from the hospital alive, 596 (6.5%) experienced prICULOS. Cumulative incidence of rehospitalization for the prICULOS cohort at 30 and 365 days was 17.5% and 45.6% versus 11.4% and 28.1% for non‐prICULOS (P<0.01). Over 40% of rehospitalizations for the entire cohort occurred within 30 days of discharge costing over

Recurrent Seizures Following Cardiac Surgery: Risk Factors and Outcomes in a Historical Cohort Study.

12 million. The most common reasons for rehospitalization were heart failure (in prICULOS) and infection (in non‐prICULOS). Rehospitalization within 30 days was associated with a 2.29‐fold risk of poor 1‐year noninstitutionalized survival for the entire cohort. Potentially modifiable factors affecting 30‐day rehospitalization included lack of physician visits within 30 days of discharge (odds ratio 2.11; P=0.01), and preoperative anxiety diagnosis (odds ratio 2.20; P=0.01). Conclusions PrICULOS patients have high rates of rehospitalization that is associated with an increased rate of poor noninstitutionalized survival. Addressing modifiable risk factors including early postdischarge access to physician services, as well as access to mental health services may improve patient outcomes.

Can long-term ventricular assist devices be safely implanted in low-volume, non-heart transplant centres?

OBJECTIVES To determine the risk factors for and outcomes after recurrent seizures (RS) in patients following cardiac surgery. DESIGN A historical cohort study. SETTING A single-center university teaching hospital. PARTICIPANTS Cardiac surgery patients from April 2003 to September 2010 experiencing postoperative seizures. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Patients were divided into an isolated seizure group and an RS group. Risk factors for RS were determined using logistic regression. Intermediate-term follow-up was conducted by phone. Of 7,280 consecutive patients undergoing cardiac surgery, 61 (0.8%) experienced postoperative seizure and 36 (59%) of those experienced at least 1 recurrence. Of these, 32 (89%) experienced RS within 24 hours of the first seizure, and 29 (81%) had grand mal seizures. Preoperative creatinine ≥120 μmol/L (p = 0.02), time until first seizure occurred (≤4 hours; p = 0.01), and procedures involving the thoracic aorta were associated with RS (R(2) = 0.53, p<0.05). Patients with RS had longer intensive care unit stays (5.3 v 2.9 days, p = 0.03) and longer mechanical ventilation duration (53.3 v 15.0 hours, p = 0.01). At a median follow-up of 21 months for the RS group and 16 months for the isolated seizure group, restrictions, anticonvulsant use, morbidity, and mortality were similar between patients with isolated versus recurrent seizures. CONCLUSIONS Higher preoperative creatinine, thoracic aortic surgery, and early seizure onset were associated with RS after cardiac surgery. When compared to isolated seizures, recurrence per se was not associated with significantly increased long-term morbidity or mortality.

Survival and Long-Term Outcomes of Aortic Valve Replacement in Patients Aged 55 to 65 Years

BACKGROUND Mechanical circulatory support (MCS) using long-term ventricular assist devices (VADs) is an established therapy in select patients with advanced heart failure. Studies have suggested that outcomes after VAD implantation may be dependent on institutional procedural volume, and outcome data from non-transplant centres are lacking. This study reviews the outcomes of patients who received a long-term VAD at our centre to determine if these devices can be safely implanted at tertiary care, low-volume, non-transplant centres. METHODS We conducted a single-centre retrospective cohort study, examining the clinical outcomes of consecutive patients who received a long-term VAD over a 42-month period. RESULTS During the study period 73 patients required MCS, of whom 16 received a long-term VAD. This select group had a mean Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile of 1.6 (0.9) and before implantation 94% required at least 1 inotropic medication, 69% had suffered a cardiac arrest, 63% required an intra-aortic balloon pump, 69% required mechanical ventilation, and 44% required short-term MCS. The primary outcome of survival to transplant or ongoing MCS at 1 year was achieved in 75% of patients. Operating room, intensive care unit, and hospital survival were 100%, 88%, and 81%, respectively. CONCLUSIONS Long-term VADs can be implanted at low-volume, nontransplant centres with survival rates comparable with contemporary clinical trials. Availability of a specialty trained multidisciplinary team with expertise in short-term and long-term MCS options facilitates appropriate patient selection and might be more important than institutional volume in determining outcomes after implantation.