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Mitral valve repair or replacement is important in the treatment of mitral regurgitation. For valve replacement, a transcatheter approach had the possibility of decrease the invasiveness of the procedure while retaining the benefit of replacement over repair. However, fluoroscopy images acquired during the procedure provide no anatomical information regarding the placement of the probe tip once the catheter has entered a cardiac chamber. By using 3D ultrasound and registering the 3D ultrasound images to the fluoroscopy images, a physician can gain a greater understanding of the mitral valve region during transcatheter mitral valve replacement surgery. In this work, we present a graphical user interface which allows the registration of two co-planar X-ray images with 3D ultrasound during mitral valve replacement surgery.

Background: Ischemic mitral regurgitation is a condition characterized by mitral insufficiency secondary to an ischemic left ventricle. Primarily, the pathology is the result of perturbation of normal regional left ventricular geometry combined with adverse remodeling. We present a comprehensive review of contemporary surgical, medical, and percutaneous treatment options for ischemic mitral regurgitation, rigorously examined by current guidelines and literature., Methods: We conducted a literature search of the PubMed database, Embase, and the Cochrane Library (through November 2018) for studies reporting perioperative or late mortality and echocardiographic outcomes after surgical and nonsurgical intervention for ischemic mitral regurgitation., Results: Treatment of this condition is challenging and often requires a multimodality approach. These patients usually have multiple comorbidities that may preclude surgery as a viable option. A multidisciplinary team discussion is crucial in optimizing outcomes. There are several options for treatment and management of ischemic mitral regurgitation with differing benefits and risks. Guideline-directed medical therapy for heart failure is the treatment choice for moderate and severe ischemic mitral regurgitation, with consideration of coronary revascularization, mitral valve surgery, cardiac resynchronization therapy, or a combination of these, in appropriate candidates. The use of transcatheter mitral valve therapy is considered appropriate in high-risk patients with severe ischemic mitral regurgitation, heart failure, and reduced left ventricular ejection fraction, especially in those with hemodynamic instability., Conclusions: The role of mitral valve surgery and transcatheter mitral valve therapy continues to evolve., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Repairing a prolapsed mitral valve that involves multiple cusps is procedurally complicated and carries a higher risk of failure when performed with individual neochordae. Inserting multiple neochordae into the papillary muscle, sizing, and aligning them in a manner that can restore coaptation is challenging. A multichordal mitral valve apparatus (MitraPatch) with a single neopapillary muscle section, 4 neochordae with each chord ending in a neoleaflet section, was developed. In this study, the 6-month outcomes of using this apparatus to repair mitral prolapse in swine is reported., Methods: Seven pigs (n = 7) with prolapse from mitral chordal transection were repaired with the device. One pig was used to develop the procedure, and 6 swine received the implant and were survived to 150 days (n = 4) and 180 days (n = 2), with monthly echocardiographic examinations. All hearts were explanted for gross necropsy and detailed histopathology., Results: Severe mitral regurgitation (MR) was observed after chordal transection in all pigs. Repairing the valve with the device reduced MR to none-or-trace levels in 3 swine, grade 1 in 3 swine, and 1 to 2+ in 1 swine immediately after surgery. In the pigs with none/trace/grade 1 MR, the device was intact and coaptation was fully restored as observed on serial echocardiograms. The device was intact, without dehiscence, stretching, or fibrosis at termination. The neoleaflet and neopapillary sections of the device elicited a host response, which is on track to produce living valve replacement tissue, but we cannot tell how controlled this might be several years later. In the pig with grade 1 to 2+ MR, accidental transection of both marginal and strut chordae in that region was observed at death, with dehiscence of the device at the site of its insertion into the leaflet., Conclusions: The anatomic principles that guide this multichordal design appear to be valid, with good hemodynamic performance and a controlled host response at 6 months., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background Undersized ring annuloplasty is a commonly used surgical repair for ischemic mitral regurgitation, in which annular downsizing corrects regurgitation, but alters valve geometry and elevates tissue stresses. In this study, we investigated if unphysiological leaflet kinematics after annuloplasty might cause pathogenic biological remodeling of the mitral valve leaflets, and if preserving physiologic leaflet kinematics with a better technique can moderate such adverse remodeling. Methods and Results Twenty-nine swine were induced with ischemic mitral regurgitation, and survivors were assigned to groups: 7 underwent annuloplasty, 12 underwent annuloplasty with papillary-muscle approximation, 6 underwent papillary-muscle approximation, and 3 were sham controls. Pre-and post-surgery leaflet kinematics were measured, and valve tissue was explanted after 3 months to assess biological changes. Anterior leaflet excursion was unchanged across groups, but persistent tethering was observed with annuloplasty. Posterior leaflet was vertically immobile after annuloplasty, better mobile with the combined approach, and substantially ( P=0.0028) mobile after papillary-muscle approximation. Procollagen-1 was higher in leaflets from annuloplasty compared with the other groups. Heat shock protein-47 and lysyl oxidase were higher in groups receiving annuloplasty compared with sham. α- SMA was elevated in leaflets from animals receiving an annuloplasty, indicating activation of quiescent valve interstitial cells, paralleled by elevated transforming growth factor-β expression. Conclusions This is the first study to demonstrate that surgical valve repairs that impose unphysiological leaflet mechanics have a deleterious, pathological impact on valve biology. Surgeons may need to consider restoring physiologic leaflet stresses as well as valve competence, while also exploring pharmacological methods to inhibit the abnormal signaling cascades.

Mitral regurgitation (MR) imposes left ventricular volume overload, triggering rapid ventricular dilatation, increased myocardial compliance, and, ultimately, cardiac dysfunction. Breakdown of the extracellular matrix has been hypothesized to drive these rapid changes, partially from an imbalance in the matrix metalloproteinases (MMPs) and their tissue inhibitors [tissue inhibitors of metalloproteinase (TIMPs)]. In the present study, we developed a rat model of severe MR that mimics the human condition and investigated the temporal changes in extracellular matrix-related genes, collagen biosynthesis proteins, and proteolytic enzymes over a 20-wk period. Male Sprague-Dawley rats were anesthetized to a surgical plane with mechanical ventilation, and a thoracotomy was performed to expose the apex. Using transesophageal ultrasound guidance, a needle was inserted into the beating heart to perforate the anterior mitral leaflet and create severe MR. Animals were survived for 20 wk, with some animals terminated at 2, 10, and 20 wk for analysis of left ventricular tissue. A sham group that underwent the same surgery without mitral leaflet perforation and MR were used as controls. At 2 wk post-MR, increased collagen gene expression was measured, but protein levels of collagen did not corroborate this finding. In parallel, MMP-1-to-TIMP-4, MMP-2-to-TIMP-1, and MMP-2-to-TIMP-3 ratios were significantly elevated, indicating a proteolytic milieu in the myocardium, possibly causing collagen degradation. By 20 wk, many of the initial differences seen in the proteolytic ratios were not observed, with an increase in collagen compared with the 2-wk time point. Altogether, this data indicates that an imbalance in the MMP-to-TIMP ratio may occur early and potentially contribute to the early dilatation and compliance observed structurally. NEW & NOTEWORTHY In this rodent model of severe mitral regurgitation that mimics the human condition, eccentric left ventricular dilatation occurred rapidly and persisted over the 20-wk period with parallel changes in myocardial collagen and matrix metalloproteinases that may drive the extracellular matrix breakdown.

Objective: We report a new expanded polytetrafluoroethylene multichordal mitral apparatus (MitraPatch) to simplify mitral repairs involving multiple cusps and sought to describe the surgical technique and demonstrate the efficacy of the device., Methods: MitraPatch was laser cut from a single sheet of expanded polytetrafluoroethylene and mounted on a custom-designed handle. Surgical technique to deploy the apparatus on the native mitral valve was developed in ex vivo porcine hearts. Hemodynamic efficacy of repairing mitral prolapse and regurgitation was assessed in ex vivo hearts and in five 30-day chronic swine, with histopathology in an additional swine at 120 days after implantation., Results: In ex vivo heart studies, leaflet coaptation was restored from 0 mm at the posterior prolapsing segment to 8.1 ± 2.2 mm after repair with the MitraPatch (P < 0.05) and to 10.2 ± 1.3 mm after the repair of the anterior leaflet (P < 0.05). In in vivo studies, valve function at 30 days was considered good, with none to trace regurgitation. Device was flexible, without tissue overgrowth or dehiscence. At 120 days, complete endothelialization was observed., Conclusions: The multichordal MitraPatch can potentially simplify complex mitral valve repairs involving multiple leaflet cusps, possibly enabling an optimal mitral repair even by surgeons without the focused high-volume experience.

Ischemic mitral regurgitation (IMR) is a frequent complication after a myocardial infarction (MI), which doubles mortality. Transcatheter mitral repairs are emerging as alternative treatment options to open heart surgery for IMR, but animal models to test them are lacking. We report a percutaneous swine model of IMR. Seventeen swine were randomized to (group 1, n = 12) MI causing IMR, and (group 2, n = 5) controls. In group 1, MI was induced via percutaneous ethanol injection into the obtuse marginal branches of the left circumflex artery, resulting in ST elevating myocardial infarction. Nine animals were survived to 8-10 weeks with weekly echocardiograms and three swine were survived to 16-20 weeks with MRI at termination. In group 1 animals, average IMR fraction at termination was 26.6 ± 2.3% in the echo group, and 24.51 ± 0.41% in the MRI group. None of the animals in group 2 had IMR. Left ventricular dysfunction and significant dilatation were evident in group 1 animals, compared to the controls. In conclusion, a reproducible model of IMR is reported for use in pre-clinical testing of new mitral technologies.

Mitral regurgitation is a common cardiac valve lesion, developing from primary lesions of the mitral valve or secondary to cardiomyopathies. Moderate or higher severity of mitral regurgitation imposes significant volume overload on the left ventricle, causing permanent structural and functional deterioration of the myocardium and heart failure. Timely correction of regurgitation is essential to preserve cardiac function, but surgical mitral valve repair is often delayed due to the risks of open heart surgery. Since correction of mitral regurgitation can provide symptomatic relief and halt progressive cardiac dysfunction, transcatheter mitral valve repair technologies are emerging as alternative therapies. In this approach, the mitral valve is repaired either with sutures or implants that are delivered to the native valve on catheters introduced into the cardiovascular system under image guidance, through small vascular or ventricular ports. Several transcatheter mitral valve technologies are in development, but limited clinical success has been achieved. In this review, we present a historical perspective of mitral valve repair, review the transcatheter technologies emerging from surgical concepts, the challenges they face in achieving successful clinical application, and the increasing rigor of safety and durability standards for new transcatheter valve technologies.

Background: Partial false lumen (FL) thrombosis is a risk factor for long-term mortality in acute type B aortic dissection (ATBAD). This study investigates FL pressures in models of ATBAD with patent and partially thrombosed FL., Methods: Twenty-five porcine aortas were used to create five models of ATBAD that were connected to a pulsatile flow loop. Models A through C had a patent FL with the following morphologies: model A, single proximal tear; model B, single distal tear; and model C, single proximal and single distal tear. Models D and E had a single proximal and a single distal tear, with partial FL thrombosis. Model D had FL occlusion of the proximal tear, and model D had FL occlusion of the distal tear. True lumen (TL) and FL pressures were measured at 90 to 150 mm Hg., Results: In model A, FL pressures were 6 mm Hg higher than TL pressures (p < 0.01). In model B, FL pressures were 10 mm Hg lower than TL pressures (p ≤ 0.01). In model C, TL and FL pressures were equivalent. In model D, FL pressures were 40 mm Hg lower than TL pressures (p < 0.001). In model E, FL pressures were 10 mm Hg higher than TL pressures (p < 0.01)., Conclusions: In a biologic model of ATBAD, the number, location, and FL thrombosis status determine FL pressure. In the setting of partial FL thrombosis, the FL pressure is reduced with proximal tear occlusion and increased with distal tear occlusion. Reduced FL pressure is related to retrograde flow., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Surgical repair of flail mitral valve leaflets with neochordoplasty has good outcomes, but implementing it in anterior and bi-leaflet leaflet repair is challenging. Placing and sizing individual neochordae is time consuming and error prone, with persistent localized flail if performed incorrectly. In this study, we report our pre-clinical experience with a novel multi-chordal patch for mitral valve repair. The device was designed based on human cadaver hearts, and laser cut from expanded polytetrafluoroethylene. The prototypes were tested in: (stage 1) ex vivo hearts with leaflet flail (N = 6), (stage 2) acute swine induced with flail (N = 6), and (stage 3) two chronic swine survived to 23 and 120 days (N = 2). A2 and P2 prolapse were successfully repaired with coaptation length restored to 8.1 ± 2.2mm after posterior repair and to 10.2 ± 1.3mm after anterior repair in ex vivo hearts. In vivo, trace regurgitation was seen after repair with excellent patch durability, healing, and endothelialization at euthanasia. A new device for easier mitral repair is reported, with good early pre-clinical outcomes.

Mitral regurgitation (MR) is a common heart-valve lesion after myocardial infarction in humans. Because it is considered a risk factor for accelerated heart failure and death, various surgical approaches and catheter-based devices to correct it are in development. Lack of a reproducible animal model of MR after myocardial infarction and reliable techniques to perform open-heart surgery in these diseased models led to the use of healthy animals to test new devices. Thus, most devices that are deemed safe in healthy animals have shown poor results in human efficacy studies, hampering progress in this area of research. Here we report our experience with a swine model of postinfarction MR, describe techniques to induce regurgitation and perform open-heart surgery in these diseased animals, and discuss our outcomes, complications, and solutions.

Mitral valve disease is a frequent cause of heart failure and death. Emerging evidence indicates that the mitral valve is not a passive structure, but--even in adult life--remains dynamic and accessible for treatment. This concept motivates efforts to reduce the clinical progression of mitral valve disease through early detection and modification of underlying mechanisms. Discoveries of genetic mutations causing mitral valve elongation and prolapse have revealed that growth factor signalling and cell migration pathways are regulated by structural molecules in ways that can be modified to limit progression from developmental defects to valve degeneration with clinical complications. Mitral valve enlargement can determine left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and might be stimulated by potentially modifiable biological valvular-ventricular interactions. Mitral valve plasticity also allows adaptive growth in response to ventricular remodelling. However, adverse cellular and mechanobiological processes create relative leaflet deficiency in the ischaemic setting, leading to mitral regurgitation with increased heart failure and mortality. Our approach, which bridges clinicians and basic scientists, enables the correlation of observed disease with cellular and molecular mechanisms, leading to the discovery of new opportunities for improving the natural history of mitral valve disease.

Background: Regional subpapillary myocardial hypokinesis may impair lateral reduction in the interpapillary muscle distance (IPMD) from diastole to systole, and adversely affect mitral valve geometry and tethering., Objectives: The goal of this study was to investigate the impact of impaired lateral shortening in the interpapillary muscle distance on mitral valve geometry and function in ischemic heart disease., Methods: To quantify ventricular size/shape, regional myocardial contraction, lateral shortening of the IPMD, mitral valve geometry, and severity of mitral regurgitation, 67 patients with ischemic heart disease underwent cardiac magnetic resonance imaging, and a correlation analysis of measured parameters was performed. The impact of reduced IPMD shortening on mitral valve (dys)function was confirmed in swine and in a physiological computational mitral valve model., Results: Lateral shortening of the IPMD from diastole to systole was severely reduced in patients with moderate/severe ischemic mitral regurgitation (9.6 ± 2.8 mm), but preserved in mild IMR (11.5 ± 3.4 mm). Left ventricular size and ejection fraction did not differ between the groups. In swine with subpapillary infarction and impaired IPMD, mitral regurgitation was evident within 1 week, compared to those pigs with a nonpapillary infarction and preserved IPMD. In the controlled computational valve model, IPMD had the maximal impact on regurgitation, and was exacerbated with additional annular dilation., Conclusions: By using cardiac magnetic resonance imaging in humans, we demonstrated that it is the impairment of lateral shortening between the papillary muscles, and not passive ventricular size, that governs the severity of mitral regurgitation. Loss of lateral shortening of IPMD tethers the leaflet edges and impairs their systolic closure, resulting in mitral regurgitation, even in small ventricles. Understanding the lateral dynamics of ventricular-valve interactions could aid the development of new repair techniques for ischemic mitral regurgitation., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To characterize the postsurgical hemodynamics in aortic valve bypass (AVB) patients, and to determine the relationship between presurgical native aortic valve pressure gradient and postsurgical hemodynamics., Materials and Methods: Twenty patients scheduled for AVB surgery underwent presurgical transthoracic Doppler echocardiography to assess the degree of aortic stenosis and postsurgical cardiac magnetic resonance imaging (MRI) to acquire phase contrast magnetic resonance (PCMR) flow values along the ascending and descending aorta, and in the conduit. Net flow values were calculated from the PCMR images and compared to presurgical aortic valve pressure gradient measurements., Results: PCMR showed that: 1) The blood flow split between the aorta and the conduit was 35%:65% of cardiac output and 2) 60% of patients had net retrograde blood flow in the superior thoracic aorta over the cardiac cycle. Patients with presurgical pressure gradient (ΔP) > 45 mmHg had significantly less blood flow out of the native aorta than patients with ΔP < 45 mmHg, and had significantly more retrograde flow in the superior thoracic aorta postsurgery., Conclusion: In patients undergoing AVB, presurgical aortic valve pressure gradient is associated with the volume of blood flow out the aorta and the direction of blood flow in the superior thoracic aorta after conduit addition as measured by PCMR., (© 2013 Wiley Periodicals, Inc.)

Aortic valve endothelial cells (ECs) function in vastly different levels of shear stress. The biomechanical characteristics of cells on each side of valve have not been investigated. We assessed the morphology and mechanical properties of cultured or native valve ECs on intact porcine aortic valve cusps using a scanning ion conductance microscope (SICM). The autocrine influence of several endothelial-derived mediators on cell compliance and the expression of actin were also examined. Cells on the aortic side of the valve are characterized by a more elongated shape and were aligned along a single axis. Measurement of EC membrane compliance using the SICM showed that the cells on the aortic side of intact valves were significantly softer than those on the ventricular side. A similar pattern was seen in cultured cells. Addition of 10(-6) M of the nitric oxide donor sodium nitroprusside caused a significant reduction in the compliance of ventricular ECs but had no effect on cells on the aortic side of the valve. Conversely, endothelin-1 (10(-10)-10(-8) M) caused an increase in the compliance of aortic cells but had no effect on cells on the ventricular side of the valve. Aortic side EC compliance was also increased by 10(-4) M of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. Immunofluorescent staining of actin filaments revealed a great density of staining in ECs on the ventricular surface. The expression of actin and the relative membrane compliance of ECs on both side of the valve were not affected by ventricular and aortic patterns of flow. This study has shown side-specific differences in the biomechanics of aortic valve ECs. These differences can have important implications for valve function.

Background and Aim of the Study: Anterior leaflet flail resulting from elongated or ruptured marginal chordae is frequently diagnosed among adults, and is amenable to surgical repair. The study aim was to investigate the efficacy of three surgical techniques, namely neochordoplasty, limited triangular resection and edge-to-edge repair, to correct anterior leaflet flail in an in-vitro experimental model., Methods: Seven porcine mitral valves were evaluated in a pulsatile heart simulator before surgical manipulation, after anterior marginal chordae transection, and with each surgical repair. Marginal chordal transection induced leaflet flail with moderate mitral regurgitation (MR). Following the confirmation of MR via direct flow measurements, it was corrected by three repairs: neochordoplasty with ePTFE sutures, limited triangular resection, and edge-to-edge repair. The post-repair valve hemodynamics were quantified under pulsatile conditions of 120 mmHg peak transmitral pressure and 5 l/min cardiac output at 70 beats/min. Hemodynamic, geometric and echocardiographic indices were also measured., Results: Transecting the marginal chordae induced A2 prolapse and produced the regurgitant fraction to 18.7 +/- 10.2%. Surgical repair effectively reduced the regurgitant fraction to 6.9 +/- 6.3% (p = 0.019 to prolapse, p = 0.0117 to baseline) with neochordae, to 5.8 +/- 7.0% (p = 0.03 to prolapse, p = 0.0378 to baseline) with triangular resection, and to 13.3 +/- 10.2% (p = 0.2091 to prolapse, p = 0.0045 to baseline) with edge-to-edge repair. Remnant regurgitation was largest with edge-to-edge repair compared to limited leaflet resection and neochordoplasty, though central leaflet coaptation was restored equally by the three repairs, with mild systolic leaflet restriction after repair., Conclusion: Anterior leaflet repair and a reduction in MR is achievable with the three techniques, although neochordoplasty and triangular resection proved superior to edge-to-edge repair in eliminating MR.

Background and Aim of the Study: Mitral valve geometry is significantly altered secondary to left ventricular remodeling in non-ischemic and ischemic dilated cardiomyopathies. Since the extent of remodeling and asymmetry of dilatation of the ventricle differ significantly between individual patients, the valve geometry and tethering also differ. The study aim was to determine if mitral valve geometry has an impact on the efficacy of surgical repairs to eliminate regurgitation and restore valve closure in a validated experimental model., Methods: Porcine mitral valves (n = 8) were studied in a pulsatile heart simulator, in which the mitral valve geometry can be precisely altered and controlled throughout the experiment. Baseline hemodynamics for each valve were measured (Control), and the valves were tethered in two distinct ways: annular dilatation with 7 mm apical papillary muscle (PM) displacement (Tether 1, symmetric), and annular dilatation with 7 mm apical, 7 mm posterior and 7 mm lateral PM displacement (Tether 2, asymmetric). Mitral annuloplasty was performed on each valve (Annular Repair), succeeded by anterior leaflet secondary chordal cutting (Sub-annular Repair). The efficacy of each repair in the setting of a given valve geometry was quantified by measuring the changes in mitral regurgitation (MR), leaflet coaptation length, tethering height and area., Results: At baseline, none of the valves was regurgitant. Significant leaflet tethering was measured in Tether 2 over Tether 1, but both groups were significantly higher compared to baseline (60.9 +/- 31 mm2 for Control versus 129.7 +/- 28.4 mm2 for Tether 1 versus 186.4 +/- 36.3 mm2 for Tether 2). Consequently, the MR fraction was higher in Tether 2 group (23.0 +/- 5.7%) than in Tether 1 (10.5 +/- 5.5%). Mitral annuloplasty reduced MR in both groups, but remnant regurgitation after the repair was higher in Tether 2. After chordal cutting a similar trend was observed with trace regurgitation in Tether 1 group at 3.6 +/- 2.8%, in comparison to 18.6 +/- 4.2% in the Tether 2 group., Conclusion: In this experimental model, the tethering geometry of the mitral valve impacts the valve hemodynamics after annuloplasty and chordal cutting. The quantitative assessment of valve geometry may help in tailoring a repair to the specific tethering pattern.

Background and Aim of the Study: Short-term postoperative warfarin therapy has been used to decrease neurologic events following mitral valve repair or bioprosthetic replacement (MVR). The study aim was to compare the short- and long-term outcomes of patients undergoing mitral valve surgery with or without short-term postoperative warfarin., Methods: A single academic US institution retrospective review was performed on discharged patients who underwent MVR between January 1996 and March 2010. Patients were allocated to two groups: MVR with four to six weeks of postoperative warfarin (n = 315; Warfarin group) or MVR without postoperative warfarin (n = 257; No warfarin group). Patients who required either preoperative or postoperative warfarin for any disease process (e.g., atrial fibrillation, mechanical valve, deep venous thrombosis) were excluded. Logistic and Cox proportional hazards regression models were constructed to evaluate the effects of warfarin on short- and long-term outcomes, respectively. Adjusted odds ratios (AOR) and adjusted hazard ratios (AHR), with 95% confidence intervals (CI) were constructed for each outcome. To reduce selection bias, propensity scoring methods were employed to balance the groups with respect to 54 preoperative variables., Results: Mean age was not significantly different between groups (No warfarin group = 56.8 +/- 14.5 years versus Warfarin group 55.9 +/- 12.9 years; p = 0.46). The average length of hospital stay was 9.8 +/- 8.4 days and 7.3 +/- 4.5 days in the No warfarin and Warfarin groups, respectively (p < 0.001). At the six-week follow up the incidences of stroke (p = 0.74), pleural effusions (p = 0.88), pericardial effusions (p = 0.75), and bleeding complications (p = 0.30) were similar between the two groups. In an unadjusted Kaplan-Meier analysis, the No warfarin group had a poorer long-term survival than the Warfarin group (p < 0.001). However, after propensity adjustment, the benefit of warfarin was not statistically significant (AHR = 0.66, 95% CI 0.40-1.08, p = 0.098)., Conclusion: The use of postoperative warfarin following MVR does not reduce the incidence of stroke at early follow up. However, there remains a trend for improved long-term outcomes in those patients receiving postoperative warfarin therapy.

Background: Surgical reconstruction of a flail posterior leaflet is a routine mitral valve repair, the techniques for which have evolved from leaflet resection to leaflet preservation. Artificial expanded polytetrafluoroethylene neochordae are frequently used to stabilize the flail leaflet and seldom, translocation of the native secondary chordae of the valve to the leaflet free edge is used. In this study, we sought to investigate the efficacy of the 2 techniques to correct posterior leaflet prolapse and reduce mitral regurgitation, and quantify the acute post repair leaflet kinematics., Methods: Adult porcine mitral valves (n =7) were studied in a pulsatile left heart experimental model in which isolated P2 flail was mimicked by marginal chordal transection. Baseline conditions were established in each valve under normal conditions (control) and were followed by induction of isolated P2 flail by transecting the 2 marginal chordae on the posterior leaflet free edge (disease). The flail posterior leaflet was reconstructed using artificial neochordae (repair 1) and then native chordal translocation (repair 2). Reduction in leaflet flail, changes in mitral regurgitation fraction, leaflet coaptation length, and posterior leaflet mobility were measured using B-mode echocardiography or color Doppler., Results: At baseline, all the valves were competent with no mitral regurgitation. After transection of the marginal chordae on the posterior leaflet, isolated P2 flail was evident with 13.7% ± 13% regurgitation. Reconstruction with artificial neochordae eliminated leaflet flail and reduced mitral regurgitation to 3.2% ± 2.8%, and with chordal translocation leaflet flail was corrected and mitral regurgitation was measured at 2.3% ± 2.6%. Using either repair techniques, leaflet coaptation and mobility of the repaired leaflets were adequate and comparable with the baseline measurements., Conclusions: Comparable reduction leaflet flail and regurgitation, and restoration of physiologic leaflet coaptation with the 2 techniques indicate that under acute conditions, use of artificial neochordae or native chordal translocations have similar benefits., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Transection of the secondary chordae on the anterior leaflet of the mitral valve to relieve leaflet tethering and reduce regurgitation is an experimentally proven procedure to correct functional mitral regurgitation. In the present study, we sought to investigate whether transecting the secondary chordae would have an effect on the marginal chordal force on the same leaflet., Methods: Adult porcine mitral valves (n = 8) were studied in a pulsatile heart simulator, in which the papillary muscle positions can be precisely positioned. Miniature transducers were inserted into the anterior marginal chordae to measure the chordal forces. Each valve was studied under baseline conditions, 3 different tethering conditions (apical, apical-lateral, and apical-lateral-posterior), and after chordal cutting in the 3 tethering conditions. The temporal changes and peak and average marginal chordal forces under each condition are reported., Results: Apical tethering increased the marginal chordal force by an average of 96% but remained unchanged after chordal cutting. With apical-lateral tethering, the marginal chordal force increased by 210% from baseline and increased further to 350% of baseline after chordal cutting. After apical-lateral-posterior tethering, the marginal chordal force increased to 335% of baseline before transection and by 548% after transection., Conclusions: The increase in the marginal chordal force after secondary chordal cutting depends on the location of the papillary muscles and the extent of leaflet tethering. Although chordal cutting might not alter the valve mechanics under minimal leaflet tethering, it significantly affects the mechanics when the leaflet tethering is more pronounced, which is typically seen in patients with functional mitral regurgitation., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Endoscopic methods to perform intracardiac procedures are of enormous interest, with the introduction of transcatheter techniques for complex cardiac procedures. In the present study, we demonstrate the use of a novel transapical cardioscopy system to visualize intracardiac structures in a porcine model., Methods: The cardioscope was designed to mount a miniature CCD camera at its tip and was covered in a blunt convex Plexiglass top that allowed displacement and visualization of the tissue in front of the cardioscope. Transapical access for 11-mm cardioscopy was performed by way of a median sternotomy (n = 4) and minithoracotomy (n = 1) in an anesthetized porcine model, and various cardiac structures were imaged under beating heart conditions. The images from the camera were projected onto a monitor for the operator to guide cardioscope positioning., Results: Video images and identification of structures on the left side of an in vivo beating porcine heart were obtained. Initially, the papillary muscle and mitral valve components were evaluated. The left atrium was entered, and the pulmonary vein orifices and atrial appendage were confirmed. Next, the camera was positioned within the left ventricle, and the ventricular portion of the trileaflet aortic valve was inspected. Using direct visualization, the camera was passed into the proximal ascending aorta. The left and right coronary arteries were also visualized. A catheter was introduced by way of a side port to confirm the position of the aortic valve leaflets during visualization. The pig experienced no significant decrease in blood pressure and maintained a stable heart rate throughout the procedure. The port was removed, and the transapical incision was closed with minimal blood loss during the procedure and closure of the orifice., Conclusions: Transapical cardioscopy is a novel approach that allows for precise visualization of intracardiac structures within a beating porcine heart without the use of cardiopulmonary bypass. This technique might allow for more successful minimally invasive valvular, intracardiac, or ascending aortic procedures without the use of radiation., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Annuloplasty for functional tricuspid regurgitation may sometimes be ineffective because of chamber dilation and valve tethering. This study compared a novel technique, right ventricle (RV)-papillary muscle approximation, with annuloplasty in experimentally-produced tricuspid regurgitation., Methods: RVs of isolated porcine hearts (n = 10) were statically pressurized, which led to RV dilation and central tricuspid regurgitation. Regurgitant flow was measured with a saline solution-filled column. The head of the anterior papillary muscle was approximated to 4 points on the ventricular septum. Next, a prosthetic ring was implanted, and then RV-papillary muscle approximation was combined. Tricuspid annular dimension, RV geometry, and tricuspid valve tethering were analyzed with 3-dimensional echocardiography., Results: Tricuspid regurgitation (2270 ± 186 mL/min) was reduced by RV-papillary muscle approximation alone (214 ± 45 mL/min; P < .05) more than by annuloplasty alone (724 ± 166 mL/min; P < .05). Combined RV-papillary muscle approximation and annuloplasty resulted in the least regurgitation (80 ± 39 mL/min). RV-papillary muscle approximation reduced tricuspid septolateral diameter (25%; P < .05), and annular area (23%; P < .05), as did annuloplasty. RV-papillary muscle approximation also reduced RV sphericity index (33%; P < .05) and tricuspid tethering height (54%; P < .05), whereas annuloplasty did not. Direction of RV-papillary muscle approximation did not independently affect outcomes., Conclusions: This ex vivo study suggests that RV-papillary muscle approximation potentially repairs tricuspid regurgitation better than annuloplasty by improving ventricular sphericity and valve tethering as well as annular dimension., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Introduction: Serotonin/5-hydroxytryptamine (5-HT) has been implicated in valve disease and in the modulation of valve mechanical properties. Several 5-HT receptor subtypes are also known to be mechanosensitive in other cell types, but this has not been studied in the context of the valve. In this study, we sought to understand the effects of elevated 5-HT levels and stretch overload on aortic valve remodeling and the dominant 5-HT receptor subtype that regulates these processes., Methods and Results: Collagen biosynthesis and tissue mechanical properties of porcine aortic valve cusps were evaluated after 10% (physiologic) and 15% (pathologic) dynamic stretch. These studies were performed in normal medium or medium supplemented with 5-HT (1, 10, 100 μM) in the absence and presence of 5-HT(2A) or 5-HT(2B) receptor antagonists. Fresh valves served as controls. Valve collagen content was maximal at the 10-μM 5-HT concentration for both 10% and 15% stretch. The 5-HT(2A) receptor antagonist reduced collagen synthesis, cell proliferation, and hsp47 expression under elevated and normal stretch, whereas the 5-HT(2B) receptor antagonist was effective only at normal stretch. The pretransition stiffness of the valve cusps was also increased in response to 5-HT via a stretch-sensitive 5-HT(2A) mechanism, with the post-transition stiffness unaltered., Conclusions: Combined elevated stretch and 5-HT resulted in increased valve collagen biosynthesis, cell proliferation, and tissue stiffness. These responses were inhibited by a 5-HT(2A) antagonist. This strongly suggests that the 5-HT(2A) receptor subtype is sensitive to elevated stretch., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The mechanical environment of the aortic valve (AV) has a significant impact on valve cellular biology and disease progression, but the regional variation in stretch across the AV leaflet is not well understood. This study, therefore, sought to quantify the regional variation in dynamic deformation characteristics of AV leaflets in the native mechanical environment in order to link leaflet stretch variation to reported AV calcification patterns., Methods: Whole porcine AVs (n=6) were sutured into a physiological left heart simulator and subjected to pulsatile and physiologically normal hemodynamic conditions. A grid of ink dots was marked on the entire ventricular surface of the AV leaflet. Dual camera stereo photogrammetry was used to determine the stretch magnitudes across the entire ventricular surface over the entire diastolic duration., Results: Elevated stretch magnitudes were observed along the leaflet base and coaptation line consistent with previously reported calcification patterns suggesting the higher mechanical stretch experienced by the leaflets in these regions may contribute to increased disease propensity. Transient stretch overloads were observed during diastolic closing, predominantly along the leaflet base, indicating the presence of a dynamic fluid hammer effect resulting from retrograde blood flow impacting the leaflet. We speculate the function of the leaflet base to act in cooperation with the sinuses of Valsalva to dampen the fluid hammer effect and reduce stress levels imparted on the rest of the leaflet., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background and Aim of the Study: Experimental models of tricuspid valve regurgitation (TR) are used to study novel annuloplasty techniques (including prosthetic rings), and they can also serve as physiologic models to investigate TR pathophysiology. The study aim was to develop an appropriate simple and reproducible experimental model of TR from annular dilatation., Methods: Acute TR was successfully created through multiple small 3- to 5-mm incisions in the annulus using a custom-made optical port with an instrument shaft (the Cardioport) that accepts a standard endoscopic imaging system. The Cardioport was inserted, via a thoracotomy, through the right atrium of seven Yorkshire pigs, and directed towards the tricuspid valve annulus to create the annular incisions. Tricuspid valve anatomy and function were evaluated using 2D and 3D echocardiography. The presence and severity of TR, annulus diameter, and changes in heart rate and atrial pressures after making the annular incisions were documented. To monitor tricuspid annular dilatation and the progression of TR, follow up echocardiography and color Doppler examinations were performed at two and eight weeks postoperatively., Results: The acute onset of TR was well tolerated, and there were no deaths or significant morbidity associated with the procedure. The annular diameter was increased from a preoperative mean of 23.1 +/- 1.7 mm, to 32.2 +/- 2.5 mm at two weeks postoperatively, and to 37.3 +/- 3.6 mm at eight weeks postoperatively. Overall, the TR progressed from mild (grade I) to severe (grade III) in all of the animals., Conclusion: This novel porcine model represents a relatively simple and a reproducible surgical technique for the creation of annular dilatation and TR, and may also serve as a chronic model of the latter condition.

The burden of heart valve disease among adults is enormous in the developed world. Increased life expectancy and age-related valvular degeneration remain the predominant contributors to heart valve dysfunction, which if uncorrected lead to congestive heart failure and increased morbidity and mortality. Clinical evidence on the detrimental impact of valve disease on both pediatric and adult populations has fueled growing interest in diagnosis and therapy for heart valve disease, and also significant financial investment from hospitals and medical device manufacturers in hybrid operating rooms and novel medical device technologies. A wide array of surgical, minimally invasive and percutaneous heart valve technologies are available today, which have significantly enlarged the surgeon's armamentarium, and revolutionized the traditional role of a surgeon in correcting such lesions. Amid this revolution in heart valve technologies, we present recent advances in heart valve therapies, critically appraise their clinical need, and finally discuss the clinical experience and outcomes of some of these technologies. The expected outcome of this review is to provide the clinical reader with a reasonable scientific basis to enable appropriate adoption of these technologies into their clinical practice.

Interest in developing durable mitral valve repair methods is growing, underscoring the need to better understand the native mitral valve mechanics. In this study, the authors investigate the dynamic deformation of the mitral valve strut chordae-to-anterior leaflet transition zone using a novel stretch mapping method and report the complex mechanics of this region for the first time. Eight structurally normal porcine mitral valves were studied in a pulsatile left heart simulator under physiological hemodynamic conditions -120 mm peak transvalvular pressure, 5 l/min cardiac output at 70 bpm. The chordal insertion region was marked with a structured array of 31 miniature markers, and their motions throughout the cardiac cycle were tracked using two high speed cameras. 3D marker coordinates were calculated using direct linear transformation, and a second order continuous surface was fit to the marker cloud at each time frame. Average areal stretch, principal stretch magnitudes and directions, and stretch rates were computed, and temporal changes in each parameter were mapped over the insertion region. Stretch distribution was heterogeneous over the entire strut chordae insertion region, with the highest magnitudes along the edges of the chordal insertion region and the least along the axis of the strut chordae. At early systole, radial stretch was predominant, but by mid systole, significant stretch was observed in both radial and circumferential directions. The compressive stretches measured during systole indicate a strong coupling between the two principal directions, explaining the small magnitude of the systolic areal stretch. This study for the first time provides the dynamic kinematics of the strut chordae insertion region in the functioning mitral valve. A heterogeneous stretch pattern was measured, with the mechanics of this region governed by the complex underlying collagen architecture. The insertion region seemed to be under stretch during both systole and diastole, indicating a transfer of forces from the leaflets to the chordae and vice versa throughout the cardiac cycle, and demonstrating its role in optimal valve function.

Background: The three-dimensional saddle shape of the mitral annulus is well characterized in animals and humans, but the impact of annular nonplanarity on valve function or mechanics is poorly understood. In this study, we investigated the impact of the saddle shaped mitral annulus on the mechanics of the P2 segment of the posterior mitral leaflet., Methods: Eight porcine mitral valves (n = 8) were studied in an in-vitro left heart simulator with an adjustable annulus that could be changed from flat to different degrees of saddle. Miniature markers were placed on the atrial face of the posterior leaflet, and leaflet strains at 0%, 10%, and 20% saddle were measured using dual-camera stereophotogrammetry. Averaged areal strain and the principal strain components are reported., Results: Peak areal strain magnitude decreased significantly from flat to 20% saddle annulus, with a 78% reduction in the measured strain over the entire P2 region. In the radial direction (annulus free edge), a 44.4% reduction in strain was measured, whereas in the circumferential direction (commissure-commissure), a 34% reduction was measured from flat to 20% saddle., Conclusions: Nonplanar shape of the mitral annulus significantly reduced the mechanical strains on the posterior leaflet during systolic valve closure. Reduction in strain in both the radial and circumferential directions may reduce loading on the suture lines and potentially improve repair durability, and also inhibit progression of valve degeneration in patients with myxomatous valve disease.

Objective: Leaflet prolapse resulting from acute chordal rupture is one presentation of fibroelastic deficiency that is associated with minimal leaflet changes in the prolapsing segment. Minimizing resection and preserving leaflet tissue may be an optimal surgical strategy. We examined the importance of the leaflet preservation concept by comparing resective and nonresective surgical procedures in practice today., Methods: Eight porcine mitral valves were evaluated in an in vitro heart simulator before surgical manipulation. Mitral regurgitation was created in these valves by transecting the posterior marginal chordae resulting in severe P2 prolapse. After confirmation of mitral regurgiation via regurgitant flow measurement (mL/beat), regurgitation was corrected by three repairs: neochordoplasty with polytetrafluoroethylene sutures (Gore-Tex; W. L. Gore & Associates, Inc, Flagstaff, Ariz), triangular resection, and quadrangular resection with annular compression. Postrepair valve hemodynamics were quantified under pulsatile conditions of 120 mm Hg peak transmitral pressure and 5 L/min cardiac output at 70 beats/min. Furthermore, hemodynamic, geometric, and echocardiographic indices were measured., Results: Transecting the marginal chordae resulted in severe P2 prolapse and significant mitral regurgiation (19.3 +/- 4.3 mL/beat). Regurgitant volume was significantly reduced after any of the three surgical approaches (quadrangular, 4.38 +/- 1.6 mL/beat; triangular, 2.56 +/- 1.0 mL/beat; neochordal, 2.86 +/- 1.24 mL/beat). In comparison with the baseline normal valves, leaflet coaptation length and posterior leaflet mobility were significantly reduced in the quadrangular resection group, whereas they were partially restored in the triangular resection and fully preserved in the neochordoplasty group., Conclusions: Although the three repair procedures are hemodynamically comparable, valve function and leaflet kinematics were significantly better after a nonresection or limited resective correction of leaflet prolapse in this experimental model of acute chordal rupture with otherwise normal leaflet geometry.

Background and Aim of the Study: A new mitral valve repair concept to treat mitral regurgitation (MR) due to valve prolapse was recently proposed. In this study, an improved design of this concept is presented, and the results of preliminary hemodynamic studies conducted in an in-vitro prolapse model are reported., Methods: The new repair approach is based on using a web/net attached to a standard annuloplasty ring spanning the annulus of the mitral valve. Experiments were conducted in a left ventricular simulator, using native porcine mitral valves. Severe MR was created by transecting the marginal chordae to induce P2 prolapse, and also by displacing the papillary muscles basally to induce bileaflet prolapse., Results: Implantation of the mitral web prevented leaflet prolapse and restored leaflet coaptation with trace mitral insufficiency, in both posterior and bileaflet prolapse. In posterior leaflet prolapse, implantation of the mitral web reduced the regurgitation volume from 10.43 +/- 3.76 ml to 2.13 +/- 1.83 ml per beat (p < 0.05). No visual damage was observed on the mitral valve leaflets after 4 h of continuous operation., Conclusion: Based on the study results, the mitral web may represent a feasible option to repair different types of mitral valve prolapse. The mitral web may also significantly simplify mitral valve repair for complex lesions.

Objective: Reoperation rates to correct left atrioventricular valve regurgitation after primary repair of atrioventricular canal defects remain relatively high. The causes of valvular regurgitation are likely multifactorial, and simple cleft closure is often insufficient to prevent recurrence., Methods: To elucidate the mechanisms leading to regurgitation, we conducted hemodynamic studies using isolated native mitral valves. Anatomy of these valves was altered to mimic atrioventricular canal type valves and studied under pediatric hemodynamic conditions. The impact of subvalvular geometry, cleft closure, annular dilatation, and annular undersizing on regurgitation were investigated., Results: Papillary muscle position did not have a significant effect on regurgitation. Cleft closure had a significant impact on valvular competence, with reduction in regurgitation volume with increased cleft closure. Regurgitation volume decreased from 12.5 +/- 2.4 mL/beat for an open cleft to 4.9 +/- 1.9 mL/beat for a partially closed cleft and to 1.4 +/- 1.6 mL/beat when the cleft was completely closed. Annular dilatation had a significant impact on regurgitation even after cleft closure. A 40% increase in annular size increased regurgitation by 59% for a partially closed cleft and by 84% for a fully closed cleft. Reducing the annular size by 20% from the physiologic level decreased the regurgitation volume by 12% for a fully open cleft and by 58% for the partially closed cleft case., Conclusions: Annular dilatation after primary repair has a potentially significant role in the recurrence of atrioventricular valve regurgitation. Reducing the annular size and restricting dilatation as an adjunct to cleft closure is a promising surgical approach in such valve anatomies.

Mechanical forces are known to affect the biomechanical properties of native and engineered cardiovascular tissue. In particular, shear stress that results from the relative motion of heart valve leaflets with respect to the blood flow is one important component of their mechanical environment in vivo. Although different types of bioreactors have been designed to subject cells to shear stress, devices to expose biological tissue are few. In an effort to address this issue, the aim of this study was to design an ex vivo tissue culture system to characterize the biological response of heart valve leaflets subjected to a well-defined steady or time-varying shear stress environment. The novel apparatus was designed based on a cone-and-plate viscometer. The device characteristics were defined to limit the secondary flow effects inherent to this particular geometry. The determination of the operating conditions producing the desired shear stress profile was streamlined using a computational fluid dynamic (CFD) model validated with laser Doppler velocimetry. The novel ex vivo tissue culture system was validated in terms of its capability to reproduce a desired cone rotation and to maintain sterile conditions. The CFD results demonstrated that a cone angle of 0.5 deg, a cone radius of 40 mm, and a gap of 0.2 mm between the cone apex and the plate could limit radial secondary flow effects. The novel cone-and-plate permits to expose nine tissue specimens to an identical shear stress waveform. The whole setup is capable of accommodating four cone-and-plate systems, thus concomitantly subjecting 36 tissue samples to desired shear stress condition. The innovative design enables the tissue specimens to be flush mounted in the plate in order to limit flow perturbations caused by the tissue thickness. The device is capable of producing shear stress rates of up to 650 dyn cm(-2) s(-1) (i.e., maximum shear stress rate experienced by the ventricular surface of an aortic valve leaflet) and was shown to maintain tissue under sterile conditions for 120 h. The novel ex vivo tissue culture system constitutes a valuable tool toward elucidating heart valve mechanobiology. Ultimately, this knowledge will permit the production of functional tissue engineered heart valves, and a better understanding of heart valve biology and disease progression.

Objectives: Mitral valve repair for degenerative diseases has shown suboptimal results in selected patients. Improved postinterventional mitral valve mechanics are essential to increase repair durability., Methods: Eight porcine mitral valves were tested in a physiologic left heart simulator under normal hemodynamic conditions. Leaflet strain was measured by tracking the displacement of a 5 x 8 marker array located on the central region of the anterior leaflet. Local leaflet strain and strain rates were calculated from measured displacements. The experiments were conducted in 4 different annular configurations associated with saddle height/commissural diameter ratios of 0%, 10%, 20%, and 30%. All experiments were conducted in the normal papillary muscle position., Results: For all annular configurations, the anterior leaflet material showed anisotropy, with the major principal strain in the radial direction and the minor principal strain in the circumferential direction. The peak major principal strain was 0.22 +/- 0.07, whereas the peak minor principal strain was 0.11 +/- 0.049 in the normal annular configuration (saddle height/commissural diameter ratio of 20%). The peak major principal strain was reduced by 13.52% +/- 12.79%, 27.53% +/- 13.65%, and 29.72% +/- 29.79% for the 10%, 20%, and 30% saddle height/commissural diameter ratio configurations, respectively, when compared with reduction for the flat annular configuration. Peak strain in the circumferential direction was unaffected by annular curvature. Reduction in areal strain of 18.62% +/- 18.98% and 27.97% +/- 35.01% were observed for the 20% and 30% saddle height/commissural diameter ratio configurations, respectively., Conclusion: The strain in the central region of the anterior leaflet is reduced with increasing annular saddle curvature. Decreased leaflet strain and associated stress might improve mitral valve repair durability.