Transcatheter Therapy for Mitral Regurgitation Clinical Challenges and Potential Solutions.

Severe mitral regurgitation is a common and complex disease that is associated with an adverse prognosis. For decades, surgical treatment has been the standard of care. Recently, multiple technologies for transcatheter mitral therapy have emerged, with the potential for both repair and replacement in patients with native mitral regurgitation. Transcatheter mitral technologies have potential as solutions for unmet clinical needs. Further rigorous clinical studies are needed to determine their efficacy and safety, as well as the appropriate patient candidates. These evaluations will help to define the role of transcatheter mitral therapy as a potentially exciting new strategy to improve the lives of patients with mitral regurgitation.

Identifying Variability in Mental Models Within and Between Disciplines Caring for the Cardiac Surgical Patient.

BACKGROUND: The cardiac operating room is a complex environment requiring efficient and effective communication between multiple disciplines. The objectives of this study were to identify and rank critical time points during the perioperative care of cardiac surgical patients, and to assess variability in responses, as a correlate of a shared mental model, regarding the importance of these time points between and within disciplines. METHODS: Using Delphi technique methodology, panelists from 3 institutions were tasked with developing a list of critical time points, which were subsequently assigned to pause point (PP) categories. Panelists then rated these PPs on a 100-point visual analog scale. Descriptive statistics were expressed as percentages, medians, and interquartile ranges (IQRs). We defined low response variability between panelists as an IQR ≤ 20, moderate response variability as an IQR > 20 and ≤ 40, and high response variability as an IQR > 40. RESULTS: Panelists identified a total of 12 PPs. The PPs identified by the highest number of panelists were (1) before surgical incision, (2) before aortic cannulation, (3) before cardiopulmonary bypass (CPB) initiation, (4) before CPB separation, and (5) at time of transfer of care from operating room (OR) to intensive care unit (ICU) staff. There was low variability among panelists' ratings of the PP "before surgical incision," moderate response variability for the PPs "before separation from CPB," "before transfer from OR table to bed," and "at time of transfer of care from OR to ICU staff," and high response variability for the remaining 8 PPs. In addition, the perceived importance of each of these PPs varies between disciplines and between institutions. CONCLUSIONS: Cardiac surgical providers recognize distinct critical time points during cardiac surgery. However, there is a high degree of variability within and between disciplines as to the importance of these times, suggesting an absence of a shared mental model among disciplines caring for cardiac surgical patients during the perioperative period. A lack of a shared mental model could be one of the factors contributing to preventable errors in cardiac operating rooms.

Early Experience With New Transcatheter Mitral Valve Replacement.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) is a potential therapy for patients with symptomatic, severe mitral regurgitation (MR). The feasibility of this therapy remains to be defined. OBJECTIVES: The authors report their early experience with TMVR using a new valve system. METHODS: The valve is a self-expanding, nitinol valve with bovine pericardial leaflets that is placed using a transapical delivery system. Patients with symptomatic MR who were deemed high or extreme risk by the local heart teams were enrolled in a global pilot study at 14 sites (United States, Australia, and Europe). RESULTS: Fifty consecutively enrolled patients (mean age: 73 ± 9 years; 58.0% men; 84% secondary MR) underwent TMVR with the valve. The mean Society for Thoracic Surgery score was 6.4 ± 5.5%; 86% of patients were New York Heart Association functional class III or IV, and the mean left ventricular ejection fraction was 43 ± 12%. Device implant was successful in 48 patients with a median deployment time of 14 min (interquartile range: 12 to 17 min). The 30-day mortality was 14%, with no disabling strokes, or repeat interventions. Median follow-up was 173 days (interquartile range: 54 to 342 days). At latest follow-up, echocardiography confirmed mild or no residual MR in all patients who received implants. Improvements in symptom class (79% in New York Heart Association functional class I or II at follow-up; p < 0.0001 vs. baseline) and Minnesota Heart Failure Questionnaire scores (56.2 ± 26.8 vs. 31.7 ± 22.1; p = 0.011) were observed. CONCLUSIONS: TMVR with the valve was feasible in a study group at high or extreme risk for conventional mitral valve replacement. These results inform trial design of TMVR in lower-risk patients with severe mitral valve regurgitation (Evaluation of the Safety and Performance of the Twelve Intrepid Transcatheter Mitral Valve Replacement System in High Risk Patients with Severe, Symptomatic Mitral Regurgitation - The Twelve Intrepid TMVR Pilot Study; NCT02322840).

Association of Guideline Adherence for Serial Evaluations With Survival and Adverse Clinical Events in Patients With Asymptomatic Severe Aortic Stenosis.

Importance: For patients with asymptomatic severe aortic stenosis and normal left ventricular function, current practice guidelines empirically recommend serial evaluations every 6 to 12 months. The benefit of this clinical monitoring is unknown. Objective: To determine the association of guideline adherence with clinical outcomes in patients with asymptomatic severe aortic stenosis. Design, Setting, and Participants: This retrospective cohort study involved 300 patients with asymptomatic severe aortic stenosis who were seen in the ambulatory Minneapolis Heart Institute at Abbott Northwestern Hospital. Rates of survival and adverse clinical events, including myocardial infarction, stroke, and heart failure hospitalization, were compared between patients who adhered to serial evaluation guidance and those who did not. Medical records were reviewed from July 25, 2007, to December 6, 2012. Data analysis took place from February 4, 2017, to July 10, 2017. Main Outcomes and Measures: All-cause mortality, heart failure hospitalization, and major adverse clinical events during follow-up. Results: The study population of 300 comprised 143 men (47.7%) and had a mean (SD) age of 78.6 (11.5) years. There were no differences in age, race/ethnicity, sex, comorbidities, insurance status, left ventricular function, and aortic stenosis severity between patients with (n = 202) and patients without (n = 98) guideline adherence. Aortic valve replacement (surgical or catheter based) was performed more frequently (54.0% vs 19.4%; P < .001) and the median (interquartile range) time for this performance was earlier (2.2 [1.2-3.6] years vs 3.5 [2.0-5.8] years; P < .001) in patients with guideline adherence. All-cause mortality was higher for nonadherent patients (hazard ratio [HR], 1.57; 95% CI, 1.07-2.30; P < .001), and these patients also had a higher rate of hospital admission for heart failure decompensation in follow-up (HR, 1.66; 95% CI, 1.27-2.18; P < .001). Four-year survival that is free from death and heart failure hospitalization was higher for adherent patients than for nonadherent patients (38.7% vs 23.3%; P < .001), and this difference remained significant in models adjusted for baseline variables (adjusted HR, 1.54; 95% CI, 1.04-2.29; P = .03). Conclusions and Relevance: The findings of this study support the need for close monitoring of patients with asymptomatic severe aortic stenosis and help to validate current guidelines for serial evaluations. These findings also support initiatives to improve guideline adherence in clinical practice.

Minimally Invasive Mitral Valve Surgery I: Patient Selection, Evaluation, and Planning.

Widespread adoption of minimally invasive mitral valve repair and replacement may be fostered by practice consensus and standardization. This expert opinion, first of a 3-part series, outlines current best practices in patient evaluation and selection for minimally invasive mitral valve procedures, and discusses preoperative planning for cannulation and myocardial protection.

Minimally Invasive Mitral Valve Surgery II: Surgical Technique and Postoperative Management.

Techniques for minimally invasive mitral valve repair and replacement continue to evolve. This expert opinion, the second of a 3-part series, outlines current best practices for nonrobotic, minimally invasive mitral valve procedures, and for postoperative care after minimally invasive mitral valve surgery.

Mechanisms of Gal(alpha)1-3Gal(beta)1-4GlcNAc-R (alphaGal) expression on porcine valve endothelial cells.

OBJECTIVE: We have previously reported that porcine valve endothelium does not express immunodetectable levels of the carbohydrate Gal(alpha)1-3Galbeta1-4GlcNAc-R (known as alphaGal), suggesting that fresh porcine valve may be immunoprivileged. In this study, we further investigated the mechanisms of alphaGal expression on porcine valve endothelial cells. METHODS: Primary cultures of porcine valvular endothelial cells were established and compared with porcine aortic endothelial cells and human vein endothelial cells. Immunoblotting, reverse transcriptase-polymerase chain reaction, and flow cytometry were used to compare the expression of alphaGal at both the protein and messenger RNA levels. RESULTS: Porcine valvular endothelial cells grew rapidly on a gelatin substrate. Similar to our previous in vivo results, valve endothelial cells expressed alphaGal much less intensely than did aortic endothelial cells. Porcine aortic endothelial cells expressed an isolectin B4 (isolectin B4 lectin Bandeiraea simplicifolia) immunodetectable band at 135 kd that was not visible on porcine valve endothelial cells or on human vein endothelial cells. Reverse transcriptase-polymerase chain reaction documented three transcripts of the alphaGal gene that were identically expressed on porcine valve and aortic endothelial cells. Furthermore, flow cytometry showed an almost identical surface profile between porcine aortic and valve endothelial cells, in contrast with human vein endothelial cells. CONCLUSIONS: Cultures of primary valve endothelial cells were established and exhibited similar phenotypic patterns in vitro to those we have previously documented in vivo. RNA and flow cytometric analyses documented no difference between the RNA expression and surface protein profile for alphaGal, although whole-cell extracts demonstrated an immunodetectable band on Western blotting that was present on aortic endothelial cells but not on valve endothelial cells. These findings clarify the mechanism of expression of alpha1,3galactosyltransferase gene expression in valve endothelial cells, suggesting that delayed rejection of fresh porcine cardiac valves may occur.

Transcriptional profiling and growth kinetics of endothelium reveals differences between cells derived from porcine aorta versus aortic valve.

OBJECTIVE: Valvular tissue and aorta calcify at different rates when placed as fresh homografts or cryopreserved allografts. Furthermore, differences between valvular endothelial cells and aortic endothelial cells are not well appreciated. We established primary cultures of valve and aortic endothelial cells derived from swine and tested transcriptional and proliferative differences on various extracellular matrices. METHODS: Transcriptional profiling was performed on primary cultures of porcine valve and aortic endothelial cells. We extracted total RNA from both cell types and created cDNA libraries. We scored for 847 genes important in signal transduction pathways, and measured their expression on valve and aortic endothelial cells. To determine if there were functional differences between aortic and valvular cells, their growth rate was determined by cell counting on various extracellular matrices. RESULTS: Of 847 genes investigated, 69 (8.1%) were transcriptionally active on aortic endothelial cells and 89 (10.5%) on valve endothelial cells. Common to both cell types were 55 genes, which represents 79.7% (55/69) of activated genes on aortic endothelial cells and 61.8% (55/89) of those in valve endothelial cells. Remarkable features of the analysis included Ephrin ligand and receptor specificity for cell type, a potential fibroblast growth factor autocrine loop in both cell types, as well as upregulation of the platelet-derived growth factor receptor in valvular cells. Aortic endothelial cells were noteworthy of upregulation of vascular endothelial cell growth factor-B and vascular cell adhesion molecule. Proliferation analysis revealed that valve endothelial cells grew more rapidly (12-fold over control) than aortic endothelial cells (3-fold over control). Furthermore, valve endothelial cells proliferated most rapidly on gelatin or collagen, whereas aortic endothelial cells were most proliferative on lysine or laminin. CONCLUSIONS: Valve and aortic endothelial cells have different transcriptional and proliferative profiles. The knowledge of these differences may be an exploitable strategy in the future rational design of artificially engineered valve surfaces and in the study of the valve antigenicity, immunogenicity and structural failure.

Current era minimally invasive aortic valve replacement: techniques and practice.

BACKGROUND: Since the first aortic valve replacement through a right thoracotomy was reported in 1993, upper hemisternotomy and right anterior thoracotomy have become the predominant approaches for minimally invasive aortic valve replacement. Clinical studies have documented equivalent operative mortality, less bleeding, and reduced intensive care/hospital stay compared with conventional sternotomy despite longer procedure times. However, comparative trials face challenges due to patient preference, surgeon bias, and the lack of a standardized minimally invasive surgical approach. METHODS: Twenty cardiothoracic surgeons from 19 institutions across the United States, with a combined experience of nearly 5000 minimally invasive aortic valve replacement operations, formed a working group to develop a basis for a standardized approach to patient evaluation, operative technique, and postoperative care. In addition, a stepwise learning program for surgeons was outlined. RESULTS: Improved cosmesis, less pain and narcotic use, and faster recovery have been reported and generally accepted by patients and by surgeons performing minimally invasive aortic valve replacement. These benefits are more likely to be verified with standardization of the procedure itself, which will greatly facilitate the design and implementation of future clinical studies. CONCLUSIONS: Surgeons interested in learning and performing minimally invasive aortic valve replacement must have expertise in conventional aortic valve replacement at centers with adequate case volumes. A team approach that coordinates efforts of the surgeon, anesthesiologist, perfusionist, and nurses is required to achieve the best clinical outcomes. By first developing fundamental minimally invasive skills using specialized cannulation techniques, neck lines, and long-shafted instruments in the setting of conventional full sternotomy, the safest operative environment is afforded to patients.