Early and mid-term outcomes of aortic annular enlargement: a systematic review and meta-analysis.

Background: There is mounting evidence at experienced centers that aortic annular enlargement (AAE) procedures are safe adjuncts to surgical aortic valve replacement (SAVR) that do not increase perioperative morbidity and mortality. This systematic review and meta-analysis aims to assess the impact of AAE procedures on mid-term outcomes after SAVR. Methods: OVID MEDLINE, OVID Embase, and Cochrane Library were searched comprehensively. Comparative studies examining adult patients undergoing SAVR with and without AAE were eligible for inclusion. Studies involving aortic root replacement, Ross procedures, and Ozaki procedures were excluded. The risk of bias was assessed according to Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I), and the quality of evidence was evaluated according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). Random effects meta-analysis facilitated the quantitative synthesis. Results: A total of 2,765 records were retrieved. After full-text review, 15 eligible studies were identified for data extraction and synthesis. The dataset included a total of 216,654 patients (AAE: 7,967; no AAE: 208,687). Only mid-term outcomes were available. In unmatched and unadjusted studies, perioperative mortality was noted to be higher in the AAE group. However, this difference was not observed in studies with matching or adjusted outcomes. In both the unmatched and unadjusted studies, and the matched and adjusted studies, there were no statistically significant differences identified regarding perioperative stroke, myocardial infarction, or permanent pacemaker implantation. Similarly, there were no statistically significant differences identified in mid-term mortality [hazard ratio (HR), 1.03; 95% confidence interval (CI): 0.95 to 1.11; P=0.49; I2=20% (matched/adjusted studies)], aortic valve reintervention [HR, 0.98; 95% CI: 0.75 to 1.27; P=0.86; I2=0% (matched/adjusted studies)], or heart failure [HR, 1.06; 95% CI: 0.86 to 1.30; P=0.58; I2=25% (matched/adjusted studies)]. Conclusions: SAVR with AAE does not appear to be associated with increased perioperative morbidity or mortality. There is no conclusive indication that AAE enhances mid-term survival, freedom from reoperation, or freedom from heart failure after SAVR.

Opening the "Black Box" for Canadian Cardiac Surgery Residency Applicants∗.

Background: This study reports on the main criteria used by Canadian cardiac surgery residency program committees (RPCs) to select applicants and the perceptions of Canadian medical students interested in cardiac surgery. Methods: A 50-question online survey was sent to all 12 Canadian cardiac surgery RPCs. A similar 52-question online survey targeted at Canadian medical students interested in applying to cardiac surgery residency programs was distributed. Data from both surveys were analyzed using descriptive statistics. Results: A total of 62% of all cardiac surgery RPC members (66 of 106) participated, including committee members from all 12 programs (range: 1-12 members per program; 9%-100% response rate per program) and 67% of program directors (8 of 12). Forty-one Canadian medical students (22 pre-clerks [54%], 2 MD/PhD students [5%], and 17 clinical clerks [41%]) participated. Committee members considered the following criteria to be most important when selecting candidates: on-service clinical performance, the interview, quality of reference letters from cardiac surgeons, and completing a rotation at the target program's institution. In contrast, the following criteria relating to the candidate were considered to be less important: wanting to practice in the city or province of training, having a connection to the program location, and personally knowing committee members. Medical students' perceptions were concordant regarding what factors are the most important but they overestimated the influence of non-clinical factors and research productivity in increasing their competitiveness. Conclusion: Canadian cardiac surgery residency programs seek applicants who demonstrate clinical excellence, as assessed by surgical rotations and reference letters from colleagues, and strong interview performance.

Contexte: Cette étude fait état des principaux critères utilisés par les comités des programmes de résidence (CPR) canadiens en chirurgie cardiaque pour sélectionner les candidats, ainsi que des perceptions des étudiants en médecine canadiens qui s'intéressent à la chirurgie cardiaque. Méthodologie: Un sondage en ligne comptant 50 questions a été envoyé aux 12 CPR canadiens en chirurgie cardiaque. Un sondage en ligne semblable (comptant 52 questions) a été distribué aux étudiants en médecine qui souhaitaient soumettre leur candidature à un programme de résidence en chirurgie cardiaque au Canada. Les données des deux sondages ont été analysées à l'aide de statistiques descriptives. Résultats: Au total, 62 % des membres de CPR en chirurgie cardiaque (66 sur 106) ont répondu au sondage, y compris des membres des comités des 12 programmes (plage : 1 à 12 membres par programme; taux de réponse de 9 à 100 % par programme) et 67 % des directeurs de programme (8 sur 12). Au total, 41 étudiants en médecine canadiens (22 en préexternat [54 %], 2 étudiants au M.D./Ph. D. [5 %] et 17 stagiaires en formation clinique [41 %]) ont répondu au sondage. Les membres du comité ont considéré les critères suivants comme étant les plus importants dans le choix de candidats : le rendement clinique en service, l'entrevue, la qualité des lettres de recommandation de chirurgiens cardiaques et la réalisation d'un stage dans l'établissement associé au programme. En revanche, les critères suivants étaient considérés comme moins importants : le désir de pratiquer dans la ville ou la province de formation, un lien avec le lieu du programme, et la connaissance personnelle de membres du co-mité. Les perceptions des étudiants en médecine concordaient quant aux facteurs les plus importants, mais les étudiants surestimaient l'influence de facteurs non cliniques et de la productivité en recherche dans l'aspect concurrentiel de leur candidature. Conclusion: Les programmes de résidence canadiens en chirurgie cardiaque recherchent des candidats forts d'une excellence clinique, évaluée par les stages en chirurgie et les lettres de recommandation de collègues, et offrant une bonne performance en entrevue.

Improved Outcomes Following the Ross Procedure Compared With Bioprosthetic Aortic Valve Replacement.

BACKGROUND: The ideal aortic valve substitute for young and middle-aged adults remains elusive. OBJECTIVES: This study sought to compare the long-term outcomes of patients undergoing the Ross procedure and those receiving bioprosthetic aortic valve replacements (AVRs). METHODS: Consecutive patients aged 16-60 years who underwent a Ross procedure or surgical bioprosthetic AVR at the Toronto General Hospital between 1990 and 2014 were identified. Propensity score matching was used to account for differences in baseline characteristics. The primary outcome was all-cause mortality. Secondary outcomes included valve reintervention, valve deterioration, endocarditis, thromboembolic events, and permanent pacemaker implantation. RESULTS: Propensity score matching yielded 108 pairs of patients. The median age was 41 years (IQR: 34-47 years). Baseline characteristics were similar between the matched groups. There was no operative mortality in either group. Mean follow-up was 14.5 ± 7.2 years. All-cause mortality was lower following the Ross procedure (HR: 0.35; 95% CI: 0.14-0.90; P = 0.028). Using death as a competing risk, the Ross procedure was associated with lower rates of reintervention (HR: 0.21; 95% CI: 0.10-0.41; P < 0.001), valve deterioration (HR: 0.25; 95% CI: 0.14-0.45; P < 0.001), thromboembolic events (HR: 0.15; 95% CI: 0.05-0.50; P = 0.002), and permanent pacemaker implantation (HR: 0.22; 95% CI: 0.07-0.64; P = 0.006). CONCLUSIONS: In this propensity-matched study, the Ross procedure was associated with better long-term survival and freedom from adverse valve-related events compared with bioprosthetic AVR. In specialized centers with sufficient expertise, the Ross procedure should be considered the primary option for young and middle-aged adults undergoing AVR.

Valve-sparing aortic root replacement: a primer for cardiologists.

PURPOSE OF REVIEW: The purpose of this article is to review the contemporary evidence supporting valve-sparing aortic root replacement as the best option for patients with aortic root aneurysms and preservable aortic valves as well as to review the technical variations and modern adjuncts of these operations that impact both short and long-term durability. RECENT FINDINGS: In patients with an aortic root aneurysm, with or without aortic valve regurgitation, valve-sparing aortic root replacement provide excellent clinical outcomes and stable valve function over several decades. Successful execution of this operation depends on careful patient selection and a thorough understanding of the anatomical and physiological relationships between the various components of the aortic root. Echocardiography remains the mainstay of imaging to determine the feasibility of valve-sparing root replacement. SUMMARY: Valve-sparing aortic root replacement is an excellent alternative to composite valve graft replacement in nonelderly patients with aortic root aneurysms. Dedicated aortic root surgeons perform several technical variations of valve-sparing procedures aimed at matching the specific aortic root disorder with the optimal operation.

In Vitro Matured Human Pluripotent Stem Cell-Derived Cardiomyocytes Form Grafts With Enhanced Structure and Function in Injured Hearts.

BACKGROUND: Human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) have tremendous promise for application in cardiac regeneration, but their translational potential is limited by an immature phenotype. We hypothesized that large-scale manufacturing of mature hPSC-CMs could be achieved through culture on polydimethylsiloxane (PDMS)-lined roller bottles and that the transplantation of these cells would mediate better structural and functional outcomes than with conventional immature hPSC-CM populations. METHODS: We comprehensively phenotyped hPSC-CMs after in vitro maturation for 20 and 40 days on either PDMS or standard tissue culture plastic substrates. All hPSC-CMs were generated from a transgenic hPSC line that stably expressed a voltage-sensitive fluorescent reporter to facilitate in vitro and in vivo electrophysiological studies, and cardiomyocyte populations were also analyzed in vitro by immunocytochemistry, ultrastructure and fluorescent calcium imaging, and bulk and single-cell transcriptomics. We next compared outcomes after the transplantation of these populations into a guinea pig model of myocardial infarction using end points including histology, optical mapping of graft- and host-derived action potentials, echocardiography, and telemetric electrocardiographic monitoring. RESULTS: We demonstrated the economic generation of >1×108 mature hPSC-CMs per PDMS-lined roller bottle. Compared with their counterparts generated on tissue culture plastic substrates, PDMS-matured hPSC-CMs exhibited increased cardiac gene expression and more mature structural and functional properties in vitro. More important, intracardiac grafts formed with PDMS-matured myocytes showed greatly enhanced structure and alignment, better host-graft electromechanical integration, less proarrhythmic behavior, and greater beneficial effects on contractile function. CONCLUSIONS: We describe practical methods for the scaled generation of mature hPSC-CMs and provide the first evidence that the transplantation of more mature cardiomyocytes yields better outcomes in vivo.

Supporting the Ross procedure: preserving root physiology while mitigating autograft dilatation.

PURPOSE OF REVIEW: The purpose of this article is to describe the optimized approach to nonrepairable aortic valve disease in young adults with a Ross procedure, while preserving the dynamic physiology of the aortic root. RECENT FINDINGS: As the techniques for supporting pulmonary autografts continue to be refined, and the applicability of the Ross procedure continues to expand, an assessment of the various techniques based on aortic root physiology is warranted. Semi-resorbable scaffolds show promise in ovine models for improving the Ross procedure. Recent long-term outcomes for the Dacron inclusion technique in comparison to more physiologic methods of support emphasize the importance of balancing the prevention of early dilatation with the preservation of root haemodynamics. As this review will synthesize, the dynamic physiology of the root may be preserved even in patients at a higher risk of autograft dilatation. SUMMARY: The favourable long-term outcomes of the Ross procedure can be partly attributed to the ability of the autograft to restore dynamism to the neoaortic root. Patient-specific modifications that respect root physiology can tailor the Ross procedure to address each patient's risk factors for early dilatation and late failure. As such, the Ross procedure should be recognized as an increasingly favourable solution for a wide spectrum of nonpreservable aortic valve disease in young adults.

The Ross procedure is an excellent operation in non-repairable aortic regurgitation: insights and techniques.

The Ross procedure is the best operation to treat aortic stenosis (AS) in young and middle-aged adults. However, its role in non-repairable aortic regurgitation (AR) remains debated since many historical series have reported an increased risk of pulmonary autograft dilatation and subsequent need for reintervention in these patients. Some have attributed these findings to an unrecognized and poorly characterized inherited genetic defect that prevents adaptive remodelling of the pulmonary autograft. Herein, we review the contemporary evidence surrounding the use of the Ross procedure in young adults with AR and put forth the argument that with proper technical refinements, the Ross procedure may still be the best operation to treat these patients. We believe that by tailoring the operation to the patient's anatomy and ensuring strict postoperative blood pressure control, one can achieve excellent results with the Ross procedure, including in this challenging patient population.

Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells.

Compact cardiomyocytes that make up the ventricular wall of the adult heart represent an important therapeutic target population for modeling and treating cardiovascular diseases. Here, we established a differentiation strategy that promotes the specification, proliferation and maturation of compact ventricular cardiomyocytes from human pluripotent stem cells (hPSCs). The cardiomyocytes generated under these conditions display the ability to use fatty acids as an energy source, a high mitochondrial mass, well-defined sarcomere structures and enhanced contraction force. These ventricular cells undergo metabolic changes indicative of those associated with heart failure when challenged in vitro with pathological stimuli and were found to generate grafts consisting of more mature cells than those derived from immature cardiomyocytes following transplantation into infarcted rat hearts. hPSC-derived atrial cardiomyocytes also responded to the maturation cues identified in this study, indicating that the approach is broadly applicable to different subtypes of the heart. Collectively, these findings highlight the power of recapitulating key aspects of embryonic and postnatal development for generating therapeutically relevant cell types from hPSCs.

Early outcomes of the Bentall procedure after previous cardiac surgery.

OBJECTIVES: We sought to evaluate the early outcomes of patients undergoing a Bentall procedure after previous cardiac surgery. METHODS: From 1990 to 2014, 473 patients underwent a Bentall procedure after previous cardiac surgery with a composite valve graft at a single institution: composite valve graft with a mechanical prosthesis (n = 256) or composite valve graft with a bioprosthesis (n = 217). Patients were excluded if their index operation was less than 30 days before the reoperation. The primary outcome was 30-day mortality. The secondary outcome was a composite of major morbidity and operative mortality: stroke, renal failure, prolonged mechanical ventilation, deep sternal infection, or reoperation during the same admission. Multivariable logistic regression was used to identify risk factors associated with the primary and secondary outcomes of interest. RESULTS: Median age was 57 (interquartile range, 44-67) years, and 349 patients (74%) were male. Median time between index surgery and reoperation was 13 (interquartile range, 8-21) years. A total of 178 patients (38%) underwent urgent or emergency intervention, 61 patients (13%) had active endocarditis/abscess, 87 patients (19%) had left ventricular ejection fraction less than 40%, and 262 patients (55%) had undergone more than 1 previous operation. Previous operations (not mutually exclusive) included coronary artery bypass grafting (n = 58, 12%), aortic valve/root replacement (n = 376, 80%) or repair (n = 36, 8%), and other surgical interventions (n = 245, 52%). Ninety-six patients (20%) had undergone coronary reimplantation during the previous operation, which consisted of a Bentall procedure in 81 patients, a Ross operation in 8 patients, a valve-sparing root replacement in 4 patients, and an arterial switch in 3 patients. At the time of the reoperative Bentall, both coronary arteries were reimplanted directly in 357 patients (77%), whereas 79 patients (17%) received at least 1 interposition graft. In 26 patients (5%), at least 1 of the native coronary arteries was oversewn and a vein graft bypass was performed. Thirty-day mortality occurred in 37 patients (7.8%), and 152 patients (32%) had major morbidity and operative mortality. On multivariable analysis, risk factors associated with increased 30-day mortality included older age and coronary reimplantation by a technique other than direct anastomosis. Indirect coronary reimplantation was also associated with a higher incidence of major morbidity and operative mortality, as were more than 1 previous cardiac operation and preoperative New York Heart Association functional class III/IV or greater. CONCLUSIONS: In the largest reported cohort of aortic root replacement after previous cardiac surgery, the reoperative Bentall procedure was associated with a significant operative risk. The need for complex coronary reimplantation techniques was an important factor associated with adverse perioperative events.

Contemporary outcomes of aortic and mitral valve surgery for rheumatic heart disease in sub-Saharan Africa.

OBJECTIVES: Rheumatic heart disease is endemic in sub-Saharan Africa. There is a paucity of data on the outcomes of valvular surgery for rheumatic heart disease in the developing world. The objective of this study was to evaluate the outcomes of aortic and mitral valve surgery for rheumatic heart disease in Ethiopia. METHODS: Between 2009 and 2017, 240 consecutive patients with rheumatic heart disease underwent aortic and/or mitral surgery at the Cardiac Center of Ethiopia in Addis Ababa. These surgeries were performed in the context of 22 international humanitarian missions. Median follow-up was 2.3 (interquartile range, 0.5-4.0) years and 96% complete. Outcomes were compared between patients who underwent mechanical valve implantation (n = 90, 38%), bioprosthetic valve implantation (n = 58, 24%), and valve repair (n = 92, 38%). RESULTS: Mean age of patients was 19 ± 8 years, and 136 patients (57%) were female. Operative mortality occurred in 5 patients (2.1%) and was not significantly different between the groups. Eleven additional patients (5%) died at follow-up, and 55 patients (23%) had at least 1 major adverse valve-related event. Propensity score-adjusted Cox regression analysis demonstrated higher rates of death in the bioprosthetic group compared with the mechanical group (hazard ratio, 8.82; 95% confidence interval, 1.64-47.39; P = .011). Survival was not significantly different between the repair and mechanical groups (hazard ratio, 1.09; 95% confidence interval, 0.17-7.16; P = .93). Likewise, rates of major adverse valve-related event were higher in the bioprosthetic group compared with the mechanical group (hazard ratio, 2.71; 995% confidence interval, 1.13-6.49; P = .025), but not significantly different between the repair and mechanical groups (hazard ratio, 1.98; 95% confidence interval, 0.89-4.39; P = .092). CONCLUSIONS: Left-sided valve surgery for rheumatic heart disease in sub-Saharan Africa is associated with acceptable perioperative outcomes, but a high incidence of major adverse valve-related event at follow-up. The use of bioprosthetic valves is associated with poor outcomes in this patient population.

BMP10 Signaling Promotes the Development of Endocardial Cells from Human Pluripotent Stem Cell-Derived Cardiovascular Progenitors.

The embryonic endocardium is essential for early heart development as it functions to induce trabecular myocardium, the first heart tissue to form, and is the source of the cells that make up the valves and a portion of the coronary vasculature. With this potential, human endocardial cells could provide unique therapeutic opportunities that include engineering biological valves and cell-based therapy strategies to replace coronary vasculature in damaged hearts. To access human endocardial cells, we generated a human pluripotent stem cell (hPSC)-derived endothelial population that displays many characteristics of endocardium, including expression of the cohort of genes that identifies this lineage in vivo, the capacity to induce a trabecular fate in immature cardiomyocytes in vitro, and the ability to undergo an endothelial-to-mesenchymal transition. Analyses of the signaling pathways required for development of the hPSC-derived endocardial cells identified a novel role for BMP10 in the specification of this lineage from cardiovascular mesoderm.

Revascularization strategies for left main coronary artery disease: current perspectives.

PURPOSE OF REVIEW: Left main coronary artery disease (LMCAD) represents a high-risk subset of coronary artery disease with significant morbidity and mortality if not treated in a timely manner. In this review, we survey the contemporary evidence on the management of LMCAD, highlight advances, and provide in-depth review of data comparing surgical and percutaneous approaches. RECENT FINDINGS: LMCAD represents a heterogeneous condition and management should be guided by key clinical and anatomic factors. In recent years, there has been a wealth of published prospective data including results of the EXCEL and NOBLE trials. Coronary artery bypass graft (CABG), remains the gold standard for optimal long-term outcomes and the greatest benefit seen in patients with higher anatomic complexity and longer life expectancy. Percutaneous coronary intervention (PCI) offers a less-invasive approach with rapid recovery. PCI is optimal in situations when surgery cannot be offered in a timely manner due to hemodynamic instability, for high-risk surgical patients, or those with limited life expectancy, if LMCAD is anatomically simple. As a result of continued technological and procedural improvements in both PCI and CABG, cardiovascular specialists possess a growing armamentarium of approaches to treat LMCAD. Thus, center specialization and use of a heart team approach are increasingly vital, though barriers remain. SUMMARY: Emerging evidence continues to support CABG as the gold standard for achieving optimal long-term outcomes in patients with LMCAD. PCI offers a more expeditious approach with rapid recovery and is a safe and effective alternative in appropriately selected candidates.