Current surgical aortic valve (AV) replacement options include bioprosthetic and mechanical heart valves (MHVs), each with inherent limitations. Bioprosthetic valves offer superior hemodynamics but suffer from durability issues, typically initiating deterioration within 7-8 years. MHVs, while durable, necessitate lifelong anticoagulation therapy, presenting risks such as severe bleeding and thromboembolic events. The need for anticoagulants is caused by non-physiological flow through the hinge area during the closed phase and large spikes of regional backflow velocity (RBV) during the closing phase that produces high shear events. This study introduces the iValve, a novel MHV designed to combine the hemodynamic benefits of bioprosthetic valves with the durability of MHVs without requiring anticoagulation. The iValve features eye-like leaflets, a saddle-shaped housing, and an optimized hinge design to enhance blood flow and minimize thrombotic risk. Fabricated using 6061-T6 aluminum and polyether ether ketone (PEEK), twelve iValve iterations were evaluated for their opening and closing dynamics. The reported top-performing prototypes demonstrated competitive performance against industry standards. The proposed iValve prototype exhibited a mean RBV of -4.34 m/s with no spikes in RBV, performing similarly to bioprosthetic valves and significantly outperforming existing MHVs. The iValve's optimized design showed a 7-10% reduction in closing time and a substantial decrease in RBV spikes, potentially reducing the need for anticoagulation therapy. This study highlights the iValve's potential to revolutionize prosthetic heart valve technology by offering a durable, hemodynamically superior solution that mitigates the drawbacks of current MHVs.

Objective: -In vitro evaluation of several prototype mechanical valves compared to present-day SAVR prosthetic valves. Method: -simulated normal cardiac pressures and flows -gravity pressure head column tester flows -recorded valve hydrodynamics and kinematics Results: -valves superior in performance to clinical controls Conclusions: -Prototype MHV candidates outperform the closing performance of present-day SAVR prosthetic valves, including bioprosthetic control. ### Competing Interest Statement Financial disclosure per coauthors HM and DG: University of British Columbia, Mitacs Accelerate, Vancouver, Canada, Karl Im, Angelo Medical LLC, LA, USA. ### Funding Statement This study was funded by University of British Columbia, Mitacs Accelerate, Vancouver, Canada, Karl Im, Angeleno Medical LLC, Los Angeles, USA ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study that is not presented in the manuscript are available upon reasonable request to the authors.

Objective To demonstrate a clear link between predicted blood shear forces during valve closure and thrombogenicity that explains the thrombogenic difference between tissue and mechanical valves and provides a practical metric to develop and refine prosthetic valve designs for reduced thrombogenicity. Methods Pulsatile and quasi-steady flow systems were used for testing. The time-variation of projected open area (POA) was measured using analog opto-electronics calibrated to projected reference orifice areas. Flow velocity determined over the cardiac cycle equates to instantaneous volumetric flow rate divided by POA. For the closed valve interval, data from quasi-steady back pressure/flow tests was obtained. Performance ranked by derived maximum negative and positive closing flow velocities, evidence potential clinical thrombogenicity via inferred velocity gradients (shear). Clinical, prototype and control valves were tested. Results Blood shear and clot potential from multiple test datasets guided empirical optimization and comparison of valve designs. Assessment of a 3-D printed prototype valve design (BV3D) purposed for early soft closure demonstrates potential for reduced thrombogenic potential. Conclusions The relationship between leaflet geometry, flow velocity and predicted shear at valve closure illuminated an important source of prosthetic valve thrombogenicity. With an appreciation for this relationship and based on our experiment generated comparative data, we achieved optimization of valve prototypes with potential for reduced thrombogenicity. Competing Interests None declared. Financial Disclosure This research has been done on a pro bono basis by all authors. Graphical Abstract Visualization of water jetting through closed mechanical heart valve under steady flow. Under pulsatile conditions, similar jet patterns near valve closure and leaflet rebound are likely. Dynamic metrics for several valves assessed in vitro are important in prediction of comparable blood cell damage and potential life-threatening thrombotic outcomes. Red star indicates moment of valve closure. ![Figure][1] CENTRAL MESSAGE A derived laboratory metric for valve closing flow velocity offers a way to rank valve models for potential blood damage. These results provide new insight and a mechanistic explanation for prior clinical observations where aortic and mitral valve replacements differ in thrombogenic potential and anticoagulation requirement. The study suggests a path forward to design and evaluate novel mechanical valve models for future development. As multiple modifications to mechanical and bioprosthetic valves have not resolved chronic shortcomings related to thrombogenicity and durability, a new development avenue was required to lead to eliminate thrombogenicity in the former and extend durability in the latter. PERSPECTIVE Prosthetic mechanical valve devices cause blood cell damage. Activation of the coagulation cascade is initiated by dynamic valve function. Design innovation focusing on valve closure behavior may reduce valve thrombogenic potential. Our study demonstrates that valve design can be empirically optimized with emphasis on that phase. SIGNIFICANCE Emphasis on open valve performance has encouraged a long-standing bias while under appreciation of the closing phase vital to identification of potential thrombogenic complications persist. Our multiple data sets are useful in challenging this bias. Dynamic motion(s) of mechanical valves and derived regional flow velocity are impacted by valve geometry. Focus on valve closure dynamics may lead to the development of potentially less thrombogenic prototype valves. Laboratory experiments support the supposition that valve regional flow velocity is associated with valve thrombogenic potential. This study compares three clinical valves and two experimental prototypes. ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes

Objective Bioprosthetic heart valves (BHVs) are commonly used in surgical and percutaneous valve replacement. The durability of percutaneous valve replacement is unknown, but surgical valves have been shown to require reintervention after 10 to 15 years. Further, smaller-diameter surgical BHVs generally experience higher rates of prosthesis–patient mismatch, which leads to higher rates of failure. Bioprosthetic aortic valves can flutter in systole, and fluttering is associated with fatigue and failure in flexible structures. The determinants of flutter in BHVs have not been well characterized, despite their potential to influence durability. Methods We use an experimental pulse duplicator and a computational fluid-structure interaction model of this system to study the role of device geometry on BHV dynamics. The experimental system mimics physiological conditions, and the computational model enables precise control of leaflet biomechanics and flow conditions to isolate the effects of variations in BHV geometry on leaflet dynamics. Results Both experimental and computational models demonstrate that smaller-diameter BHVs yield markedly higher leaflet fluttering frequencies across a range of conditions. The computational model also predicts that fluttering frequency is directly related to leaflet thickness. A scaling model is introduced that rationalizes these findings. Conclusions We systematically characterize the influence of BHV diameter and leaflet thickness on fluttering dynamics. Although this study does not determine how flutter influences device durability, increased flutter in smaller-diameter BHVs may explain how prosthesis–patient mismatch could induce BHV leaflet fatigue and failure. Ultimately, understanding the effects of device geometry on leaflet kinematics may lead to more durable valve replacements.

![Figure][1]</img> Background A thrombogenic potential metric was used to compare prosthetic valve models in vitro. Methods Valves were tested in aortic and mitral sites under pulsatile circulation in a pulse duplicator. An optical approach measures dynamic valve area. Pulsatile fluid dynamics were measured by conventional techniques and a quasi-steady flow tester was used to measure valve leakage. Regurgitant flow velocity was derived using time-dependent volumetric flow rate / dynamic valve area. Since flow velocity and fluid shear force are related through flow velocity gradient, thrombogenic potential for valves that achieve near closure during the forward flow deceleration phase were determined as regurgitant flow velocities relative to the control mechanical valve regurgitant flow velocity of −126 m/s. Analysis of the flow velocity data made use of Vioplot R* and VISIO software packages to provide split violin plots that represent probability of recurrence of data. Results Thrombogenic potential was made dimensionless and ranged between −0.45 and +1.0. Negative thrombogenic potentials arise when transient rebound of valve occluder is accompanied by water-hammer phenomena. Positive thrombogenic potentials occur during decelerating forward flow. Bioprostheses had lowest thrombogenic potential transient of 0.15. A mock-transcatheter aortic valve replacement incorporating by design a trivial paravalvular leak (∼1.35 ml/s) demonstrated a high transient thrombogenic potential of 0.95. Conclusions Our data reveals distinct thrombogenic potential profile differences between valve models. If our study methods are verifiable, the design of future valves may utilize currently available experimental tools to produce advanced devices with significantly reduced thrombogenic potential. Highlights ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research has been done on a pro bono basis by all authors with no financial support of others. ### Author Declarations All relevant ethical guidelines have been followed and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Not Applicable Any clinical trials involved have been registered with an ICMJE-approved registry such as ClinicalTrials.gov and the trial ID is included in the manuscript. Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant Equator, ICMJE or other checklist(s) as supplementary files, if applicable. Not Applicable All data relevant to the study are included in the article or uploaded as supplementary information. * BHV : bioprosthetic heart valve BV3D : rapid prototype bileaflet mechanical valve (3D printed) HITS : high intensity trancranial signal ml/s : milliliters per second m/s : meters per second ms : milliseconds mTAVR : mock-transcatheter aortic valve replacement MHV : mechanical heart valve PDVA : projected dynamic valve area PVL : paravalvular leakage RFV : regurgitant flow velocity s : second SJM : St Jude Medical TP : thrombogenic potential VIA : viscoelastic impedance adapter [1]: pending:yes

Computer modeling and simulation (CM&S) is a powerful tool for assessing the performance of medical devices such as bioprosthetic heart valves (BHVs) that promises to accelerate device design and regulation. This study describes work to develop dynamic computer models of BHVs in the aortic test section of an experimental pulse duplicator platform that is used in academia, industry, and regulatory agencies to assess BHV performance. These computational models are based on a hyperelastic finite element extension of the immersed boundary method for fluid--structure interaction (FSI). We focus on porcine tissue and bovine pericardial BHVs, which are commonly used in surgical valve replacement. We compare our numerical simulations to experimental data from two similar pulse duplicators, including a commercial ViVitro system and a custom platform related to the ViVitro pulse duplicator. Excellent agreement is demonstrated between the computational and experimental results for bulk flow rates, pressures, valve open areas, and the timing of valve opening and closure in conditions commonly used to assess BHV performance. In addition, reasonable agreement is demonstrated for quantitative measures of leaflet kinematics under these same conditions. This work represents a step towards the experimental validation of this FSI modeling platform for evaluating BHVs.

This in vitro study compares mechanical (MHV) and bioprosthetic (BHV) heart valves for high amplitude short duration regional flow velocities (RFV) near valve closure.We previously tested several clinical and prototype valves and observed RFV at levels which may be related to a dimensionless thrombogenic potential (TP).A total of four valves were tested in aortic and mitral sites under pulsatile circulation in a pulse duplicator. Valves included both clinical models and experimental prototypes. An optical approach measuring projected dynamic valve area (PDVA) to gauge valve motion was implemented. Pulsatile pressures and flow rates were measured by conventional techniques and a quasi-steady flow tester was used to measure valve leakage. RFV was derived using time-dependent volumetric flow rate/PDVA. Since flow velocity and fluid shear force are related through flow velocity gradient, TPs for valves that achieve near closure during the forward flow deceleration phase were determined as RFVs relative to the control mechanical valve RFV value of −126 m/s.TP is dimensionless and ranged between −0.45 and +1.0. Negative TPs arise when transient rebound of valve occluders is accompanied by water-hammer phenomena. Positive TPs occur during the decelerating forward flow. Bioprostheses had lowest TP transient of 0.15 with exception of a mock-transcatheter aortic valve (mTAVI) that incorporated by design a trivial perivalvular leak (∼1.35 ml/s). This device demonstrated a remarkably high transient TP of 0.95. The control mechanical valves had the highest TP of 1.0. The study implicates TP transients near mechanical valve closure, and not forward or non-flow phases, as primary to shear induced activation of the coagulation cascade.Our data reveals distinct TP profile differences between valve models. If verifiable, the design of future valves may utilize currently available experimental tools to determine TPs resulting in advanced devices with significantly reduced TP.

Valvular heart disease remains a large public health problem for all societies; it attracts the attention of public health organizations, researchers and governments. Valve substitution is an integral part of the treatment for this condition. At present, the choice of valve prosthesis is either tissue or mechanical. Tissue valves have become increasingly popular in spite of unresolved problems with durability, hemodynamics, cost and need for anticoagulation therapy. As a consequence, mechanical valve innovation has virtually ceased; the last successful mechanical design is 25 years old. We postulate that with improved technology, knowledge and experience gained over the last quarter century, the best possible solution to the problem of valve substitution can be achieved with a mechanical valve that is anticoagulant independent, durable, hemodynamically and cost efficient. At present, it is possible to design, test and produce a valve that can accomplish these goals.

Background: Exploration for causes of prosthetic valve thrombogenicity has frequently focused on forward or post-closure flow detail. In prior laboratory studies, we uncovered high amplitude flow velocities of short duration close to valve closure implying potential for substantial shear stress with subsequent initiation of blood coagulation pathways. This may be relevant to widely accepted clinical disparity between mechanical and tissue valves vis-a-vis thrombogenicity. With a series of prototype leaflet mechanical valves, we attempt reduction of closure related velocities with the objective of identifying a prototype valve with thrombogenic potential similar to our tissue valve control. This iterative design approach may find application in preclinical assessment of valves for anticoagulation independence.Methods: Tested valves included: prototype mechanical bi-leaflet BVs (n=56), controls (n=2) and patented early prototype mechanicals (n=2) from other investigators. Pulsatile and quasi-steady flow systems were used for testing. Projected dynamic valve area (PDVA) was measured using previously described novel technology. Flow velocity over the open and closing periods was determined by volumetric flow rate/PDVA. For the closed valve interval, use was made of data obtained from quasi-steady back pressure/flow tests. Performance was ranked by a proposed thrombogenicity potential index (TPI) relative to tissue and mechanical control valves.Results: Optimization of the prototype valve designs lead to a 3-D printed model (BV3D). For the mitral/aortic site, BV3D has lower TPI (1.10/1.47) relative to the control mechanical valve (3.44/3.93) and similar to the control tissue valve (ideal TPI <= 1.0).Conclusions: Using unique technology, rapid prototyping and thrombogenicity ranking, optimization of experimental valves for reduced thrombogenic potential was expedited and simplified. Innovative mechanical valve configurations were identified that merit consideration for further development which may bring the anticoagulation independent mechanical valve within reach.

BACKGROUND Significant paravalvular leakage after transcatheter aortic valve implantation (TAVI) correlates with increased morbidity and mortality, but adverse consequences of trivial paravalvular leakage have stimulated few investigations. Using a unique method distinctly different from other diagnostic approaches, we previously reported elevated backflow velocities of short duration (transients) in mechanical valve closure. In this study, similar transients were found in a transcatheter valve paravalvular leakage avatar. METHODS Paravalvular leakage rate (zero to 58 mL/second) and aortic valve incompetence (volumetric back flow/forward flow; zero to 32%) were made adjustable using a mock transcatheter aortic valve device and tested in quasi-steady and pulsatile flow test systems. Projected dynamic valve area (PDVA) from the back illuminated mock transcatheter aortic valve device was measured and regional backflow velocities were derived by dividing volumetric flow rate by the PDVA over the open and closing valve phase and the total closed valve area derived from backflow leakage. RESULTS Aortic incompetence from 1-32% generated negative backflow transients from 8 to 267 meters/second, a range not dissimilar to that measured in mechanical valves with zero paravalvular leakage. Optimal paravalvular leakage was identified; not too small generating high backflow transients, not too large considering volume overload and cardiac energy loss caused by defective valve behavior and fluid motion. CONCLUSIONS Thrombogenic potential of transcatheter aortic valves with trivial aortic incompetence and high magnitude regional backflow velocity transients was comparable to mechanical valves. This may have relevance to stroke rate, asymptomatic microembolic episodes and indications for anticoagulation therapy after transcatheter valve insertion.

Each year, approximately 50,000 aortic valve replacement operations are performed in the United States, but despite decades of development, many of the limitations of aortic valve prostheses remain consequences of the fluid dynamics induced by the replacement valve. We aim to develop detailed fluid-structure interaction (FSI) models of aortic valve prostheses mounted within a ViVitro Systems, Inc. pulse duplicator. Here, we describe numerical methods for simulating FSI with rigid structures, such as the leaflets of a mechanical heart valve, and we present initial three-dimensional simulation studies of the fluid dynamics of a St. Jude Regent bileaflet valve prosthesis.

BACKGROUND AND AIM OF STUDY:The results of recent hematological studies have suggested that, under non-physiological flow conditions, circulating procoagulant proteins activate the coagulation cascade. In the present study, in-vitro estimates of flow transients at or near the time of valve closure, including regional backflow velocity (RBV, m/s), flow acceleration (m/s2), and rate of acceleration (jerk, m/s3), have shed new light on the blood-damage potential of prosthetic valves.METHODS:Several prosthetic valves were tested in a pulse duplicator under simulated cardiac conditions. A unique prototype subsystem (Leonardo(VSI)) was used to measure the projected dynamic valve areas (PDVAs) from backlit valves. The regional flow velocity was derived by dividing the time-dependent volumetric flow rate by the PDVA. The flow acceleration and jerk were subsequently obtained as time derivatives of the flow velocity.RESULTS:Current mechanical valves have overt flow transients at valve closure, relating to leaflet nonresponse to flow deceleration and residual PDVA. In contrast, tissue valves initiate closure during the flow deceleration phase, and seal when closed, thus preventing supra-physiological backflow transients. The estimated average RBV transients at or near closure ranged from 45 to 162 m/s for mechanical valves, and from 3 to 10 m/s (i.e., ca. 93% less) for tissue valves. The average derived flow acceleration and jerk transients ranged from +2,235 to -1,786xg and from +10.8 x 106 to -7.5 x 10(6) m/s3 for mechanical valves, respectively, and were substantially lower for tissue valves (ca. 90-99% less).CONCLUSION:The study results implicate that RBV transients at or near mechanical valve closure, and not the forward or closed flow phase, as being primary to the shear-induced activation of the coagulation cascade. Results obtained in vitro for an experimental trileaflet mechanical valve (Triflo) were tested only in the aortic site similar to those obtained with tissue valves.

"Science without conscience is just ruin of the soul."—François Rabelais, physician and writer,Gargantua, 15341Rabelais F. Gargantua and Pantagruel. Urquhart T, Le Motteux, translators. Random House, New York1994Google Scholar From the early 1960s to the late 1990s, prosthetic heart valve designs were improved through intense scientific and clinical feedback. Mechanical heart valves, however, still require warfarin-based anticoagulation, whereas long-term durability remains a concern for bioprosthetic heart valves, particularly in young adults and children. Thus the current patient age guidelines for tissue versus mechanical valve implants typically specify recipient ages older than 65 years for tissue valves and younger than 65 years for mechanical valves. Recent meta-analyses have shown that overall and event-free survivals are similar for patients receiving mechanical and biologic aortic valves.2Lund O. Bland M. Risk-corrected impact of mechanical versus bioprosthetic valves on long-term mortality after aortic valve replacement.J Thorac Cardiovasc Surg. 2006; 132: 20-26Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 3Stassano P. Di Tommaso L. Monaco M. Iorio F. Pepino P. Spampinato N. et al.Aortic valve replacement: a prospective randomized evaluation of mechanical versus biological valves in patients ages 55 to 70 Years.J Am Coll Cardiol. 2009; 54: 1862-1868Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar Selection of a valve device is therefore based on a patient's individual life expectancy, ability to take anticoagulants, lifestyle, risk of bleeding, and risk of reoperation. Operative mortality with conventional surgery is low, even in octogenarians, and outcomes at 10 to 15 years and longer are satisfactory. A recent study of 1000 minimally invasive aortic valve replacements reported on a large subgroup of elderly patients (>80 years) with an operative mortality of 1.7%, a median hospital stay of 8 days, and an actuarial survival at 5 years of 84%.4Tabata M. Umakanthan R. Cohn L. Bolman R.M. Shekar P.S. Chen F.Y. et al.Early and late outcomes of 1000 minimally invasive aortic valve operations.Eur J Cardiothorac Surg. 2008; 33: 537-541Crossref PubMed Scopus (137) Google Scholar Commercially available valves are still based on concepts largely unchanged from the 1970s and 1980s, with unmet needs for more durable tissue valves and less thrombogenic mechanical valves. These needs are urgent worldwide for patients younger than 65 years. In particular, the need is greatest for juveniles and young adults in emerging countries and for those requiring mitral valve replacement.5Zilla P. Brink J. Human P. Bezuidenhout D. Prosthetic heart valves: catering for the few.Biomaterials. 2008; 29: 385-406Crossref PubMed Scopus (156) Google Scholar Sadly, efforts to achieve these high-priority goals seem largely to have ceased, perhaps because of short-term financial considerations. This situation is even more paradoxic now that advanced techniques in fluid mechanics and molecular biology have identified, analyzed, and quantified causes of the thrombogenic potential of current mechanical valves. Indeed, considerable evidence has become available on pathologic kinematics at valve opening and closure,6Scotten L.N. Walker D.K. New laboratory technique measures projected dynamic area of prosthetic heart valves.J Heart Valve Dis. 2004; 13: 120-133PubMed Google Scholar nonphysiologic flow patterns, vortex shedding, turbulence, abnormal flow (separation, stagnation, deceleration), energy loss, squeeze flow, microbubble formation, solid emboli, and vapor cavitation, leading to improved understanding of the link between traumatic forces applied to blood elements, activation of the coagulation cascade, and thromboembolic complications.7Wolf L.G. Choudhary B.P. Abu-Omar Y. Taggart D.P. Solid and gaseous cerebral microembolization after biologic and mechanical aortic valve replacement: investigation with multirange and multifrequency transcranial Doppler ultrasound.J Thorac Cardiovasc Surg. 2008; 135: 512-520Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 8Bluestein D. Chandran K.B. Manning K.B. Towards non-thrombogenic performance of blood recirculating devices.Ann Biomed Eng. 2010; 38: 1236-1256Crossref PubMed Scopus (57) Google Scholar Moreover, it has been demonstrated that these functional liabilities can be substantially reduced by improvements in valve design and that a durable mechanical bioprosthesis not requiring lifelong anticoagulation may be within reach.9Govindarajan V. Udaykumar H.S. Chandran K.B. Two-dimensional simulation of flow and platelet dynamics in the hinge region of a mechanical heart valve.Ann Biomech Eng. 2009; 131 (031002)Google Scholar, 10Dasi L.P. Simon H.A. Sucosky P. Yoganathan A.P. New frontiers in biomedical engineering. Fluid mechanics of artificial heart valves.Clin Exp Pharmacol Physiol. 2009; 36: 225-237Crossref PubMed Scopus (182) Google Scholar Instead, creative industrial energy has focused on catheter-based valve delivery systems to implant devices currently applicable to a small number of patients needing heart valve replacement. The recent article by Mack,11Mack M. Fool me once, shame on you; fool me twice, shame on me! A perspective on the emerging world of percutaneous heart valve therapy.J Thorac Cardiovasc Surg. 2008; 136: 816-819Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar "Fool Me Once, Shame on You; Fool Me Twice, Shame on Me! A Perspective on the Emerging World of Percutaneous Heart Valve Therapy," stimulated great interest in this subject. There is no doubt that patients prefer less invasive procedures and that a quest for better quality of life encourages adoption of novel medical devices. Heart valve replacement is a lifesaving procedure, however, and "surgery [is] an act of authority on destiny," as René Leriche put it.12Leriche R. Philosophie de la chirurgie. Flammarion, Paris, France1951Google Scholar Prosthetic heart valves must satisfy stringent technical requirements in terms of safety and efficacy. Despite sophistication of delivery technology, it is quite challenging for catheter-based valve therapy to conform to these requirements. At the same time, it is important to overcome traditional medical conservatism, as ironically described by C. Walton Lillehei in his "seven steps of innovation."13Lillehei C.W. New ideas and their acceptance. As it has related to preservation of chordae tendinea and certain other discoveries.J Heart Valve Dis. 1995; 4: S106-S114PubMed Google Scholar This ethical dilemma is exacerbated when financial interests are involved. The absolute criterion should therefore remain that the ultimate benefit to the patient should be "here and now." This leads to 3 crucial questions regarding applicability of transcatheter valve therapy: (1) Can it be done? (2) Should it be done? (3) How can it best be done? Of these 3 phases of technologic evolution, transcatheter valves appear to be entering phase 2, whereas traditional valve replacement has been in phase 3 for many years. Many patients with end-stage severe aortic stenosis are not referred for surgery ostensibly because of advanced age or major comorbidity. These patients are often left with suboptimal strategies, such as balloon valvuloplasty. To provide a better therapeutic alternative for these high-risk patients with otherwise inoperable disease, percutaneous catheter-borne valve technology was introduced. Although this option is rapidly developing, there are growing concerns about its extension to patients at lower risk. In an aging population, the number of patients with severe aortic stenosis and reduced life expectancy is increasing. It has been established that at least 1 of every 3 patients with severe aortic stenosis has no symptoms. In the absence of symptoms, the management of these patients is challenging. Frequently, they are not offered surgery because mortality and the yearly risks of prosthetic valve complications are greater than the yearly risks of watchful waiting. Without aortic valve replacement, their survival is favorable: 99%, 98%, and 93% at 1, 2, and 5 years, respectively.14Bonow R.O. Carabello B.A. Chatterjee K. de Leon A.C. Faxon D.P. Freed M.D. et al.2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association task force on practice guidelines (writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease): endorsed by the Society for Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.Circulation. 2008; 118: e523-e661Crossref PubMed Scopus (1089) Google Scholar Current practice guidelines do not recommend surgery for these patients, who may remain free of symptoms for many years. Approximately a third of all patients with asymptomatic aortic stenosis show symptoms within 2 years, however, and the prognosis may worsen significantly when symptoms develop. It has been shown that only a minority of those with potentially operable aortic valve stenosis undergo surgery. As recent findings indicate, however, octogenarians may live a lifespan comparable to that of the normal population after biologic aortic valve replacement.15Piper C. Hering D. Kleikamp G. Korfer R. Horstkotte D. Valve replacement in octogenarians: arguments for an earlier surgical intervention.J Heart Valve Dis. 2009; 18: 239-244PubMed Google Scholar In Europe, 2 catheter-delivered valves have received CE approval. In the United States the PARTNER-USA trial is under way comparing outcomes for the Edwards-SAPIEN transcatheter-delivered valve with those of standard aortic valve replacement in high-risk patients and with those of medical therapy, including aortic valvuloplasty, for patients who are not surgical candidates. Study candidates must be selected by 2 surgeons and 1 cardiologist. Interestingly, patients who are offered surgery but decline are excluded. A similar randomized study of the percutaneous CoreValve delivery system is expected to begin soon. When mortality and clinical outcomes of transcatheter valves compare favorably with those of medical therapy alone or conventional surgery, there is no doubt this specific growing population of elderly, high-risk patients could be candidates for that new therapeutic option. Potential extension of transcatheter valve implantation to lower risk patients with extended life expectancies along a path similar to that observed with coronary stenting deserves, however, the following observations. First, coronary and vascular stents were initially introduced in the clinical arena for the easiest cases. Subsequently, some interventionalists extended use to multivessel disease, bifurcations, left main disease, renal and carotid arteries, and so on. Reports of restenosed lesions encouraged adoption of new stent models before evidence of long-term efficacy. This "earn-while-you-learn" aberration eroded traditional evidence-based decision making. Currently, transcatheter valve replacement is only proposed for high-risk patients otherwise restricted to medical therapy alone. Second, coronary stents and prosthetic heart valves are passive devices. Unlike stents, however, prosthetic heart valves must withstand wide ranging dynamic stress and cyclic loading for many years. Valve substitutes must also comply with the stringent requirements of the international norm (ISO 5840) that mandates a systematic risk analysis and risk reduction to the very minimum. To our knowledge, this regulatory issue has not as yet been resolved for transcatheter-inserted valves. Recent US Food and Drug Administration Advisory Panel comments are pertinent. "In contrast, the developing field of percutaneous heart valve insertion demands innovative trial designs to address difficult new concerns. These concerns include defining target populations; establishing the correct risk/benefit ratio based on a new balance between safety and effectiveness perceived for the reduction in surgical risk; and choice of appropriate endpoints for assessment. Although innovative trial design may be necessary in certain cases of new technology, the most appropriate study design remains a randomized controlled trial as the gold standard."16Chen E. Sapirstein W. Ahn C. Swain J. Zuckerman B. Perspective on clinical trial design for cardiovascular devices.Ann Thorac Surg. 2006; 82: 773-775Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar There is a tacit assumption that durability for catheter-delivered tissue valves will be similar to that of current, conventional tissue valves, but this has yet to be determined. For the standard stented porcine and pericardial valve, durability appears to be between 10 and 20 years. The freedoms from structural valve failure are 70% to 90% at 10 years and 50% to 80% at 15 years, but substantially less in younger patients.17Siddiqui R.F. Abraham J.R. Butany J. Bioprosthetic heart valves: modes of failure.Histopathology. 2009; 55: 135-144Crossref PubMed Scopus (156) Google Scholar Bicuspid aortic valve malformations typically calcify earlier and more intensively than do archetypal aortic valves, are often associated with ascending aortic wall pathology, and are considered a contraindication for percutaneous or transapical replacement. It is estimated these valves represent more than 50% of all aortic stenosis cases in industrialized societies,18Zegdi R. Achouh P. Fabiani J.N. Percutaneous aortic valve replacement with the CoreValve bioprosthesis.J Thorac Cardiovasc Surg. 2008; 135: 1407-1408Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar and operative therapy will clearly remain the treatment of choice for the foreseeable future. The risk–benefit ratio of transcatheter valves for high-risk patients (Society of Thoracic Surgeons score >10%) with less than 5 years of life expectancy could be acceptable.19Vahanian A. Alfieri O. Al-Attar N. Antunes M. Bax J. Cormier B. et al.Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI).Eur J Cardiothorac Surg. 2008; 34: 1-8Crossref PubMed Scopus (243) Google Scholar For this population of patients, current studies20Chiam P. Ruiz C.E. Percutaneous transcatheter aortic valve implantation: assessing results, judging outcomes, and planning trials: the interventionalist perspective.JACC Cardiovasc Interv. 2008; 1: 341-350Abstract Full Text Full Text PDF Scopus (39) Google Scholar suggest that mortality and short-term morbidity could be competitive with conventional surgery, although the exact relevance of these studies remains to be established. Finally, extension of transcatheter aortic valve indications to younger patients who are candidates for mechanical valve replacement would increase the potential for a "valve-in-valve" replacement or other experimental procedures. The demonstration of safety and efficacy of these procedures may require substantial additional time and very likely cannot be repeated more than once. It should be noted that even in the elderly population, conventional reoperative valvular surgery has been performed with less than 11% mortality.21Maganti M. Rao V. Armstrong S. Feindel C.M. Scully H.E. David T.E. Redo valvular surgery in elderly patients.Ann Thorac Surg. 2009; 87: 521-525Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar For catheter-delivered valves, transfemoral and transapical approaches both require rapid ventricular pacing, critical anesthetic management of hypotension and arrhythmias during beating-heart valve implantation, and transesophageal echocardiography. Although transcatheter aortic valve insertion may become a valuable therapeutic option for high-risk patients with severe aortic stenosis and short life expectancy, it will still carry considerable risk.22Walther T. Dewey T. Borger M.A. Kempfert J. Linke A. Becht R. et al.Transapical aortic valve implantation: step by step.Ann Thorac Surg. 2009; 87: 276-283Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar In the best case, wider application of transcatheter aortic valve implantation will require much more time and additional study, including head-to-head comparisons with conventional valve replacement and apicoaortic bypass in diverse risk populations. Those familiar with heart valve history will remember that many new designs had encouraging early performance, leading to erroneous projections of durability and patient benefits. In fact, only a few valves have withstood the test of time, and patients unfortunate enough to have received less safe and effective prostheses paid the price in mortality, morbidity, and additional surgery. It is also worth remembering that failed valve designs far outnumber those that proved successful. In response to approvals for catheter-delivered valve devices and other concerns, health authorities in Belgium have recently expressed specific recommendations: "Today, reimbursement of percutaneous aortic valves cannot be defended because of the many unsolved questions regarding safety of patients and the lack of a target population. Published data are not convincing regarding the fact that the risk associated with the procedure of percutaneous valve implant could be less than the regular surgical procedure.… The high mortality at 6 months questions the safety of this procedure. The medical community should be well informed on the fact that the CE mark does not indicate a device is safe for clinical use."23Van Brabandt H. Neyt M. Safety of percutaneous aortic valve insertion. A systematic review.BMC Cardiovasc Disord. 2009; 9: 45Crossref PubMed Scopus (21) Google Scholar Whereas large financial investments presently involved in transcatheter valve delivery technologies are devoted to the elderly population, little recently has been done for the much larger population of younger patients and children worldwide who need a durable heart valve substitute that performs safely without warfarin anticoagulation.24Takkenberg J.J. Rajamannan N.M. Rosenhek R. Kumar A.S. Carapetis J.R. Yacoub M.H. et al.The need for a global perspective on heart valve disease epidemiology. The SHVD working group on epidemiology of heart valve disease founding statement.J Heart Valve Dis. 2008; 17: 135-139PubMed Google Scholar It is probable that catheter-based valve technology will result in an attractive option for a specific segment of the valve replacement population. We believe, however, that it is also important for industry to focus on development of improved devices for the great majority of patients needing valve replacement. As we have all known, it is difficult to make something simple. Comment on editorial by Lapeyre and colleaguesThe Journal of Thoracic and Cardiovascular SurgeryVol. 141Issue 2PreviewTo the Editor: Full-Text PDF

The study of heart valve performance (healthy, diseased, and prosthetic) has traditionally involved the examination of transvalvular characteristics, such as pressure gradients and effective and geometric orifice areas. However, recent research has shown that a key downstream flow characteristic, vortex ring formation, should not be overlooked because quantifying this mechanism provides insight into the assessment of valve performance [1]. Vortex ring formation, which is dependent on the valve design [1], is the roll-up of the shear layers shedding past valve leaflets. Governed by a universal time-scale or formation number (FN) that is based on the jet length to diameter ratio (L/D), vortex ring formation provides insight into the kinematics of optimizing effective fluid transport. It has been shown that growth of the leading vortex ring ceases at a FN between 3.5 and 4.5 in various biological systems [2], but most of these studies have assumed a constant or fixed orifice opening. However, incorporating a time-varying jet diameter rather than the constant valve annulus diameter has recently been identified by Dabiri and Gharib as a key factor in the characterization of vortex ring formation and provides a more complete picture of impulse generation and efficiency in vortical flows [2]. This dynamic formation number is governed by the following equation: (L/D)*=∫0tU¯/D¯dt(1) where U is velocity, D is diameter, t is time, and the overbar indicates a time average. Estimating (L/D)* can serve as a powerful evaluation tool in comparison to conventional methods of FN calculation that use either an averaged diameter or the valve annulus diameter. Ideally suited for unsteady flows, such as the opening phase and leaflet motions in heart valves, (L/D)* can provide insight into assessing the performance of natural and prosthetic heart valves (PHVs).

Background Insufficient data describe the relationship of hemodynamic parameters to left ventricular (LV) diastolic flow propagation velocity (Vp) measured using color M-mode Doppler echocardiography. Methods An in vitro LV model used to simulate LV diastolic inflow with Vp measured under conditions of varying: 1) Stroke volume, 2) heart rate (HR), 3) LV volume, 4) LV compliance, and 5) transmitral flow (TMF) waveforms (Type 1: constant low diastasis flow and Type 2: no diastasis flow). Results Univariate analysis revealed excellent correlations of Vp with stroke volume (r = 0.98), LV compliance (r = 0.94), and HR with Type 1 TMF (r = 0.97). However, with Type 2 TMF, HR was not associated with Vp. LV volume was not related to Vp under low compliance, but inversely related to Vp under high compliance conditions (r = -0.56). Conclusion These in vitro findings may help elucidate the relationship of hemodynamic parameters to early diastolic LV filling.

The in vitro function of six tissue valves from four manufacturers has been assessed. One porcine bioprosthesis (Carpentier-Edwards supra-annular) and five pericardial valves (Edwards,* Hancock, Ionescu-Shiley, Ionescu-Sbiley low-profile, and Mitral Medical Mitroflow) were tested. Valve function was measured in a pulse duplicator simulating conditions of sinus rhythm (60, 80, and 120 beats/min and stroke volume 70 ml) and supraventricular tachycardia (200 beats/min and stroke volume 30 ml). Under each of these test conditions, mean transvalvular pressure, regurgitation, and transvalvular energy loss were determined and used to compare valve function. The porcine valve showed the largest mean transvalvular pressure during forward flow. The total energy loss of this valve, however, was not the largest for the valves tested. The total transvalvular energy loss ranged between 3% and 12% for all valves and conditions. For all valves, energy loss and regurgitation were greatest during simulated tachycardia.

A simple, inexpensive rotating prism camera constructed from readily available materials using standard machining techniques has been constructed. The camera can record up to 100 pictures on 35 mm format at a rate of 50,000 per second. A pulsed ruby laser is used as a light source giving exposure times of approximately 50 nanoseconds. The performance of this camera in recording the movement of shock waves and particle tracers in a shock tube is described.