Exploring the role of epicardial adipose-tissue-derived extracellular vesicles in cardiovascular diseases.

Epicardial adipose tissue (EAT) is a fat depot located between the myocardium and the visceral layer of the epicardium, which, owing to its location, can influence surrounding tissues and can act as a local transducer of systemic inflammation. The mechanisms upon which such influence depends on are however unclear. Given the role EAT undoubtedly has in the scheme of cardiovascular diseases (CVDs), understanding the impact of its cellular components is of upmost importance. Extracellular vesicles (EVs) constitute promising candidates to fill the gap in the knowledge concerning the unexplored mechanisms through which EAT promotes onset and progression of CVDs. Owing to their ability of transporting active biomolecules, EAT-derived EVs have been reported to be actively involved in the pathogenesis of ischemia/reperfusion injury, coronary atherosclerosis, heart failure, and atrial fibrillation. Exploring the precise functions EVs exert in this context may aid in connecting the dots between EAT and CVDs.

Commissural repositioning in bicuspid aortic valve repair: an in vitro acute model to explore and explain different results.

OBJECTIVES: Commissural orientation <160° is a recognized risk factor for bicuspid aortic valve repair failure. Based on this observation, repairing this subtype of aortic valve by reorienting the 2 commissures at 180° has recently been proposed. METHODS: Nine porcine hearts with aortic annulus diameters of 25 mm were selected. A pathological model of a Sievers 1 bicuspid aortic valve was obtained by suturing the coaptation line between the left and right leaflets. Each heart underwent reimplantation procedures both in the native (120°) and the reoriented (180°) configuration. After the operation, each sample was tested on a pulse duplicator at rest (heart rate 60 beats per min) and with mild exercise (heart rate 90 beats per min) conditions. RESULTS: No statistically significant difference was noted in mean and peak transvalvular aortic gradients between the 2 configurations at rest (18.6 ± 5 vs 17.5 ± 4 for the mean aortic gradient; 42.8 ± 12.7 vs 36.3 ± 5.8 for the peak aortic gradient) but the group with the 120°-oriented commissures had significantly higher mean transaortic gradients compared to the group with the 180°-oriented commissures at initial exercise stress conditions (30.1 ± 9.1 vs 24.9 ± 3.8; p value 0.002). CONCLUSIONS: The 180° commissural reorientation of the asymmetrical bicuspid aortic valve does not improve the transvalvular aortic gradient in an acute model at rest conditions, but it could do so under stress situations. Even if it is surgically more complex and time-consuming, this approach could be a good strategy to improve long-term results, particularly in young patients.

Open supra-aortic revascularization and arch reconstruction after previous TEVAR in a complex arch anatomy.

We propose a technique to minimize the neurological and systemic risks involved in rerouting the blood flow toward the brain in a "single remaining vessel" configuration with a 90% stenosis by means of complete hypothermic cerebral protection associated with normothermic systemic blood flow with a "restitutio ad integrum" of the supra-aortic trunks flow. The perfusion of the brain and the arms was almost completely separated from the systemic perfusion by the deployment 1 year before of a thoracic endoprosthesis in association with complete chronic occlusion of the brachiocephalic trunk and a functioning carotid-subclavian bypass. The Free Flow of the prosthesis, which acted as a hook, moved the calcium toward the left carotid ostium, creating a 90% stenosis with intermittent acute cerebral hypoperfusion and amaurosis. We achieved an optimal result: The patient was discharged on postoperative day 7 with no neurological problems and with patency and direct blood flow in all the supra-aortic trunks.

How to recycle a misused left internal thoracic artery: Tips and tricks.

In this case report, we describe how to recycle the left internal thoracic artery (LITA) when misused but not damaged. Eight years after a left anterior small thoracotomy followed by left anterior descending (LAD) stenting for STEMI in first postoperative day, a 67-years-old woman had an NSTEMI with angiographic evidence of intrastent re-stenosis with a perfectly patent LITA, harvested only from the fourth to the sixth intercostal space. During redo surgery, LITA was harvested as a pedicle from the anastomosis to the fourth intercostal space and primarily from the first to the fourth intercostal space. Special attention was paid at the level of the fourth intercostal space where the vessel was stuck to the sternum: a 15-blade was used being scissors or cautery too dangerous. At the end of harvesting, the LITA was full-length available for a new coronary anastomosis on LAD, distal to the previous one.

Ex Vivo Model of Functional Mitral Regurgitation Using Deer Hearts.

Transcatheter therapies are emerging for functional mitral regurgitation (FMR) treatment, however there is lack of pathological models for their preclinical assessment. We investigated the applicability of deer hearts for this purpose.8 whole deer hearts were housed in a pulsatile flow bench. At baseline, all mitral valves featured normal coaptation. The pathological state was induced by 60-minutes intraventricular constant pressurization. It caused mitral annulus dilation (antero-posterior diameter increase from 31.8 ± 5.6 mm to 39.5 ± 4.9 mm, p = 0.001), leaflets tethering (maximal tenting height increase from 7.3 ± 2.5 mm to 12.7 ± 3.4 mm, p < 0.001) and left ventricular diameter increase (from 67.8 ± 7.5 mm to 79.4 ± 6.5 mm, p = 0.004). These geometrical reconfigurations led to restricted mitral valve leaflets motion and leaflet coaptation loss. Preliminary feasibility assessment of two FMR treatments was performed in the developed model.Deer hearts showed ability to dilate under constant pressurization and have potential to be used for realistic preclinical research of novel FMR therapies. Graphical abstract figure legend: Deer heart mitral valve fiberscopic and echocardiographic images in peak systole at baseline and after inducing the pathological conditions representing functional mitral regurgitation. In the pathological conditions lack of coaptation between the leaflets, enlargement of the antero-posterior distance (red dashed line) and the left ventricular diameter (orange dashed line) were observed.

Preoperative Computed Tomography Scan Analysis of Interleaflets Triangles to Guide Aortic Root Repair Procedures.

BACKGROUND: Stabilization of the ventriculo-aortic junction (VAJ) is gaining increasing interest in the context of aortic valve repair, since its dilation is a well-recognized risk factor for long-term repair failure. Interleaflets triangles are key elements of the VAJ, but cannot be completely visualized using echocardiography. A three-dimensional (3D) reconstruction of electrocardiogram-triggered computed tomography (CT) scan images allows an analysis of the real dimensions and anatomic characteristics of the subcommissural triangles. METHODS: A method was developed to visualize the interleaflets triangle at the CT-scan based on multiplanar post-processing reconstructions. Attention was focused on the triangles' apical angle evaluation. The data obtained with CT-scan reconstructions were compared with those collected in a previous post-mortem study to validate this measurement method. RESULTS: In the CT-scan group the angles between the left and right coronary sinuses, and the right non-coronary and left non-coronary sinuses were 46.23 ± 7.79°, 47.38 ± 6.97°, 45° [range: 42.75- 50.75°], respectively, and in the post-mortem group were 45.44 ± 12.39°, 48.31 ± 1218°, 50.25 ± 7.29°. No statistically significant differences between the two groups were identified (p = 0.84, 0.81, and 0.23). CONCLUSIONS: Based on experience acquired in the operating room, the acute-angle subcommissural triangles were considered normal, the equilateral triangles mildly dilated, and the obtuse triangles severely dilated. According to this classification, different reparative approaches were selected. A CTscan 3D reconstruction method, as validated by the present data, allows a preoperative evaluation of the triangles and VAJ in order to best plan a surgical reparative approach tailored to a single patient.

Comparison of the Performance of a Sutureless Bioprosthesis With Two Pericardial Stented Valves on Small Annuli: An In Vitro Study.

BACKGROUND: Aortic valve replacement has evolved recently with the development of the sutureless bioprosthesis. One such valve is the Perceval bioprosthesis, which is built by mounting leaflets of bovine pericardium to a thin stent; this approach has the potential to provide an excellent fluid dynamic performance. We undertook an in vitro study to compare the hydrodynamic performance of the sutureless bioprosthesis with two standard pericardial stented bioprostheses (Crown and Magna). METHODS: Tests were conducted using a mock loop, testing on two sizes of the three prostheses. The prosthesis sizes were chosen to house the valves in porcine aortic roots with a native annulus diameter of 19 mm (n = 6) or 21 mm (n = 6). The stroke volume ranged from 25 mL to 105 mL at a simulated heart rate of 70 beats per minute. RESULTS: Mean pressure drop and energy loss rose with increasing stroke volume in all of the valves tested (p < 0.001), with the sutureless valve showing the lowest values for both variables (p < 0.001). Effective orifice area values were stable across the stroke volume intervals and were larger in the sutureless valves (p < 0.001). CONCLUSIONS: All of the valves tested provided good fluid dynamic performances. The sutureless bioprosthesis provided the best performance with the least hindrance to flow behavior. From the hydrodynamic perspective, the sutureless prosthesis may present an advance in the evolution of bioprostheses, ensuring low gradients and potential for low incidence of patient-prosthesis mismatch even in small annuli.

Design of a simple coronary impedance simulator for the in vitro study of the complex coronary hemodynamics.

Several novel approaches were recently developed to treat aortic root pathologies. The alteration induced by some of these approaches to the biomechanics of the aortic root could possibly affect the coronary perfusion, compromising the procedural outcome. In this scenario, the need to replicate in vitro the coronary flow pattern in physiological and pathological conditions is becoming crucial for the functional assessment of novel devices and techniques. This article describes the design of an easy-to-use, left-and-right coronary impedance simulator, coupled with native aortic roots for in vitro pulsatile tests. Experiments were performed in order to assess the performances of the coronary impedance simulator when coupled with healthy aortic valves (cardiac output: 3.8 ± 0.26 l min-1; mean systemic pressure: 95 ± 1.3 mmHg; mean coronary flow rate: 272 ± 13.4 ml min-1) or with regurgitant valves (cardiac output: 1.9 ± 0.24 l min-1; mean systemic pressure of 45 ± 3.3 mmHg; mean coronary flow rate:149 ± 21.9 ml min-1). The acute systemic response to valve regurgitation was also replicated, with increased beat rate and afterload, aimed at restoring the systemic pressure (cardiac output: 2.5 ± 0.23 l min-1; mean systemic pressure of 109 ± 6.1 mmHg; mean coronary flow rate: 262 ± 35.5 ml min-1). In the test conditions, the system was able to replicate in vitro the main determinants of the coronary circulation with physiological left/right coronary flow rate repartition, and a realistic interaction between coronary and systemic hemodynamics. The coronary simulator appears to be a suitable platform to study and optimize the interactions between novel approaches to aortic valve pathology and the coronary perfusion.

Transcatheter Edge-to-Edge Treatment of Functional Tricuspid Regurgitation in an Ex Vivo Pulsatile Heart Model.

BACKGROUND: Although associated with left heart pathologies, functional tricuspid regurgitation (FTR) is often left untreated during left heart surgery. Hence, owing to its degenerative character, reoperation is often needed, encompassing an impressive (25% to 35%) mortality rate. Thus transcatheter approaches to FTR are raising great interest. OBJECTIVES: The authors evaluated the post-treatment effectiveness of the edge-to-edge technique using the percutaneous mitral valve repair device in an ex vivo pulsatile model of FTR. METHODS: The devices were implanted in 11 porcine hearts simulating FTR. In each heart, single-clip treatments involved grasping leaflet pairs in the medial or commissural position (6 combinations). Two-clip treatments were then performed considering all possible 15 combinations of leaflet pairs and medial/commissural grasping. Cardiac output, mean pulmonary pressure, and mean diastolic valve pressure gradient were evaluated in physiological and simulated pathological conditions (FTR), and post-treatments. RESULTS: Grasping the septal and anterior leaflets allowed for the best post-procedural outcome, ensuring a complete re-establishment of physiological-like hemodynamics. Septal and posterior grasping induced a significant recovery from FTR, although less marked. Conversely, grasping the anterior and posterior leaflets did not reduce FTR, and was detrimental in some specific cases. CONCLUSIONS: This experimental work demonstrated that the transcatheter edge-to-edge repair technique is a feasible approach for FTR. The study investigated this approach to develop a selective, specific structural intervention methodology for treating FTR, considering the several biomechanical factors that alter proper functionality of valvular substructures. These results can be used to guide the development of edge-to-edge repair techniques in treatment of FTR.

Opening-closing pattern of four pericardial prostheses: results from an in vitro study of leaflet kinematics.

Pericardial and porcine stented aortic valves have different leaflet kinematics. To study the biomechanics of a prosthesis thoroughly, the in vitro setting is the most appropriate. The aim of our study was to find out whether the prosthesis design in which the pericardial sheet is outside the stent post might influence the opening and closing patterns of the leaflets. Four pericardial prostheses (Magna Ease [MG] 21, Trifecta [TRI] 21, Soprano-Armonia [SA] 20 and Mitroflow [MF] 23) that fitted aortic roots with a native annulus diameter of 2.1 cm were implanted and their leaflet kinematics was studied by a high-speed digital camera. In the opening phase, MG showed the shortest RVOT and the highest RVOVI, with values of 12 ± 2 and 209 ± 17 ms, respectively. The RVOT of MG was significantly shorter than that of MF (p < 0.01), but not than that of TRI (p = 0.286). Both TRI and SA showed similar opening patterns (TRI: RVOT of 15 ± 3 ms and RVOVI of 132 ± 25 ms; SA: 17 ± 2 ms and 126 ± 19 ms), without statistically significant difference. Conversely, MF showed the slowest profile, with an RVOT of 23 ± 3 ms and an RVOVI of 94 ± 8 ms (Table 1; Fig. 3). The opening/closing profile is not influenced by the position of the pericardial leaflets, but depends on other intrinsic structural characteristics related to the material used for the stent and leaflets. Moreover, the kinematics does not affect the valve performance. Table 1 Kinematics and hydrodynamic results, reported as means and standard deviations, evaluated over the tested heart samples TRI SA MG MF ANOVA TRI versus SA TRI versus MG TRI versus MF SA versus MG SA versus MF MG versus MF p Value p Value p Value p Value p Value p Value p Value ET (ms) 1.0 1.0 1.0 1.0 RVOT (ms) 15 ± 3 17 ± 2 12 ± 2 23 ± 3 <0.01 1.0 0.286 <0.01 0.03 <0.01 <0.01 SVCT (ms) 247 ± 14 231 ± 15 256 ± 26 241 ± 11 0.170 0.463 0.853 0.931 0.213 1.0 1.0 RVCT (ms) 35 ± 19 52 ± 13 32 ± 17 52 ± 4 0.07 0.474 1.0 0.494 0.236 1.0 0.247 TVCT (ms) 283 ± 10 283 ± 19 289 ± 10 293 ± 11 0.584 1.00 1.0 1.0 1.0 1.0 1.0 RVOVI (ms-1) 132 ± 25 126 ± 19 209 ± 17 94 ± 8 <0.01 0.959 <0.01 0.02 <0.01 0.07 <0.01 SVCVI (ms-1) -0.9 ± 0.3 -1.1 ± 0.4 -0.57 ± 0.1 -0.55 ± 0.1 <0.01 1.0 0.353 0.292 0.045 0.04 1.0 RVCVI (ms-1) -16 ± 4 -10 ± 2 -18 ± 6 -10 ± 1 <0.01 0.396 1.0 0.513 0.025 1.0 0.03 Δp (mmHg) 6.7 ± 3.6 10.6 ± 5.5 15.2 ± 7.9 10.7 ± 6.1 <0.01 0.01 <0.01 0.01 0.04 1.0 <0.01 EOA (cm2) 2.2 ± 1.2 1.7 ± 0.9 1.5 ± 0.8 1.7 ± 0.9 <0.01 0.03 <0.01 0.01 0.261 0.617 0.11 El  % 7.3 ± 1 11.9 ± 1 15.4 ± 2 11.8 ± 3 <0.01 <0.01 <0.01 <0.01 0.04 1.00 0.03 CO (L/min) 3.1 ± 0.4 2.8 ± 0.5 3.1 ± 0.3 3.0 ± 0.5 0.534 0.282 0.792 0.702 0.106 0.552 0.559 ET ejection time, RVOT rapid valve-opening time, SVCT slow valve-closing time, RVCT rapid valve-closing time, TVCT total valve-closing time, RVOVI rapid valve-opening velocity index, SVCVI slow valve-closing velocity index, RVCVI rapid valve-closing velocity index, Δp mean pressure drop, EOA effective orifice area, El % energy loss, CO cardiac output.

A geometric approach to aortic root surgical anatomy.

OBJECTIVES: The aim of this study was the analysis of the geometrical relationships between the different structures constituting the aortic root, with particular attention to interleaflet triangles, haemodynamic ventriculo-arterial junction and functional aortic annulus in normal subjects. METHODS: Sixteen formol-fixed human hearts with normal aortic roots were studied. The aortic root was isolated, sectioned at the midpoint of the non-coronary sinus, spread apart and photographed by a high-resolution digital camera. After calibration and picture resizing, the software AutoCAD 2004 was used to identify and measure all the elements of the interleaflets triangles and of the aortic root that were objects of our analysis. Multiple comparisons were performed with one-way analysis of variance for continuous data and with Kruskal-Wallis analysis for non-continuous data. Linear regression and Pearson's product correlation were used to correlate root element dimensions when appropriate. Student's t-test was used to compare means for unpaired data. Heron's formula was applied to estimate the functional aortic annular diameters. RESULTS: The non coronary-left coronary interleaflets triangles were larger, followed by inter-coronary and right-non-coronary ones. The apical angle is <60° and its standard deviation can be considered an asymmetry index. The sinu-tubular junction was shown to be 10% larger than the virtual basal ring (VBR). The mathematical relationship between the haemodynamic ventriculo-arterial junction and the VBR calculated by linear regression and expressed in terms of the diameter was: haemodynamic ventriculo-arterial junction = 2.29 VBR (diameter) + 47. DISCUSSION: Conservative aortic surgery is based on a better understanding of aortic root anatomy and physiology. The relationships among its elements are of paramount importance during aortic valve repair/sparing procedures and they can be useful also in echocardiographic analysis and in computed tomography reconstruction.

Reimplantation Technique: A New Approach to Increase Aortic Valve Coaptation.

The reimplantation technique is one of the most popular valve-sparing procedures. Previously published in-vitro studies have demonstrated the success of the aortic interleaflets triangle reshaping approach in increasing the coaptation surface. An alternative positioning of the pledgeted stitches used in the proximal suture line of the David operation is proposed to simultaneously stabilize the annulus and improve the valve functional reserve in case of annulo-aortic ectasia due to dilation of the interleaflet triangles.

A Comprehensive Fluid Dynamic and Geometric Study for an "In-Vitro" Comparison of Four Surgically Implanted Pericardial Stented Valves.

BACKGROUND AND AIM OF THE STUDY: Many variables may affect the fluid dynamic of an implanted bioprosthesis. In-vitro studies have provided accurate data such that, when different prostheses are implanted in the same true aortic root, it should be possible to make a fair comparison. The study aim was to evaluate the fluid dynamic and geometric characteristics of the four most widely used stented pericardial bioprostheses. METHODS: Four types of pericardial prosthesis (Magna Ease 21, Trifecta 21, Soprano-Armonia 20, and Mitroflow 23) that fitted eight aortic roots with a native annulus diameter of 2.1 cm were implanted and tested in a mock loop. RESULTS: Energy loss and mean gradients were increased with stroke volume (SV) in all valves tested. The effective orifice area values were fairly stable across the SV intervals (p = 0.57). All hemodynamic-related indices displayed mutually consistent behaviors, with Trifecta showing the lowest hindrance to flow. Both geometric orifice area (GOA) and edge geometric orifice area (eGOA) were increased significantly as the SV increased; the Trifecta valve showed the largest eGOA value, while the Trifecta and Mitroflow provided the largest GOAs. For the Trifecta and Soprano-Armonia prostheses (and the Magna to a lesser extent), the most distal cross-section was systematically greater than the inflow area, suggesting a divergent configuration at the systolic peak. CONCLUSION: The study results combined the fluid dynamic reproducibility of the in-vitro setting and the specificity of surgery. A quantitative comparison of the fluid dynamic performance of the different bioprostheses was feasible.

Fluid-dynamic results of in vitro comparison of four pericardial bioprostheses implanted in small porcine aortic roots.

OBJECTIVES: Small-sized aortic bioprostheses may cause high postoperative gradients. In clinical practice, it is difficult to compare bioprostheses from different manufactures, owing to the discrepancy between the true size and the nominal size of the prosthesis and the inter-patient variability in aortic root characteristics. In vitro studies provide accurate data, and using a system in which it is possible to implant bioprostheses in a true aortic root should enable a fair comparison to be made. The present study compared the four most widely used pericardial stented bioprostheses from different manufacturers surgically implanted in small annulus, to detect any differences in their fluid-dynamic performance. METHODS: The four types of bioprostheses, each implanted in a randomized sequence in eight porcine aortic roots, with a native annulus of 2.1 cm, were tested in a mock loop at 65 ml of stroke volume by calculating hydrodynamic parameters, namely mean pressure drop and effective orifice area, performance index, valve resistance and % of energy loss. The prostheses that fitted the aortic root after sizing were as follows: a Magna Ease 21, a Trifecta 21, a Soprano-Armonia 20 and a Mitroflow 23. RESULTS: Effective orifice areas were 1.57 ± 0.2, 1.77 ± 0.2, 2.3 ± 0.3 and 1.75 ± 0.2 cm(2) (P < 0.001) for Magna Ease, Mitroflow, Trifecta and Soprano-Armonia, respectively. The mean gradients were 13.2 ± 3, 10.2 ± 3, 6.1 ± 2 and 9.6 ± 2 mmHg (P < 0.001) for Magna Ease, Mitroflow, Trifecta and Soprano-Armonia, respectively. The performance indices were 0.50 ± 0.06, 0.63 ± 0.08, 0.89 ± 0.13 and 0.56 ± 0.07 (P < 0.001) for Magna Ease, Mitroflow, Trifecta and Soprano-Armonia, respectively. The valve resistance, expressed in (dyn*s/cm(5)), was 69 ± 16, 55 ± 13, 33 ± 10 and 51 ± 11 (P < 0.001) for Magna Ease, Mitroflow, Trifecta and Soprano-Armonia, respectively. The percent of energy loss was 13.5 ± 0.5, 10.7 ± 2.5, 6.6 ± 1.6, 10.9 ± 1.8 (P < 0.001) for Magna Ease, Mitroflow, Trifecta and Soprano-Armonia, respectively. CONCLUSION: Our study combined the fluid-dynamic reproducibility of the in vitro study with, by using porcine aortic roots, the specificity of surgery. The results confirmed that bioprostheses are inherently obstructive compared with the native aortic valve and showed that bioprostheses with the pericardium outside the stent are more efficient.

In vitro study of a standardized approach to aortic cusp extension.

PURPOSE: Cusp extension technique (CET) is a reparative surgical procedure for restoring aortic valve function by suturing patches to the compromised native leaflets. Its outcomes are strongly dependent on the ability of the surgeon. We proposed and tested a novel approach on an in vitro model, aimed at standardizing and simplifying the surgical procedure. METHODS: A set of standard pre-cut bovine pericardium patches, available in different sizes, was developed. The surgeon can choose the leaflet-specific patches to be implanted according to the patient anatomy, using a geometrical model of the aortic valve whose inputs are the measured intercommissural distances. The hemodynamic performance of this approach was evaluated on porcine aortic roots in a pulsatile mock loop. Hydrodynamic and kinematic evaluation of the samples was provided. RESULTS: After CET, mean and maximum pressure drops were 3.1±1.3 mmHg and 25.4±5.0 mmHg respectively, and EOA was 3.8±0.8 cm. CONCLUSIONS: Our approach to cusp extension proved to be reliable and effective in restoring valve functioning, without significantly altering the physiological kinematics. The use of pre-cut patches considerably simplified the surgery, increasing standardization and repeatability.

In-vitro study of a porcine quadricuspid aortic valve.

BACKGROUND AND AIM OF THE STUDY: Quadricuspid aortic valve (QAV) is an extremely rare congenital defect in which the valve features an additional fourth cusp. It is often associated with an alteration in valve functionality such as valve regurgitation, stenosis and coronary disease. These associated pathologies entail surgical correction in about 50% of patients at a mean age of 50 years. METHODS: A swine QAV was studied in a pulsatile mock loop in the laboratory. Rest (70 bpm) and exercise (100 bpm) conditions were simulated, and opening and closing kinematics were evaluated from a high-speed video. Short- and long-axis echocardiograms were recorded. The pressure drop across the valve, valve competence and effective orifice area were evaluated and compared to data from healthy samples tested in the same experimental apparatus. RESULTS: Hemodynamic quantities were physiologic-like, despite the QAV showing an altered kinematics (longer closing and opening times compared to healthy samples) and an asynchronous closing phase (the extra cusps reached the closed configuration at the end of systole systematically earlier with respect to the other three cusps). Echocardiographic data showed an increased coaptation height between the left and right coronary cusps, and a mismatch between the lunule of the extra cusp and the non-coronary cusp. CONCLUSION: The altered kinematics, together with incorrect coaptation, can alter the biomechanics of the structure, inducing an anomalous distribution of local stress which could lead to structural failure over time.