ANALYZING MORPHOLOGICAL FACTORS IN THE SELECTION OF PROSTHETIC DEVICES FOR TAVR: A CASE STUDY REVIEW By Snober Shoukat Dr. Ashwini Pardiker A thesis submitted to the School of Radiologic Sciences in collaboration with a research agenda team In partial fulfillment of the requirements for the degree of MASTER OF SCIENCE IN RADIOLOGIC SCIENCES (MSRS) WEBER STATE UNIVERSITY Ogden, Utah December 15, 2023 THE WEBER STATE UNIVERSITY GRADUATE SCHOOL SUPERVISORY COMMITTEE APPROVAL of a thesis submitted by Snober Shoukat Dr. Ashwini Pardiker This thesis has been read by each member of the following supervisory committee and by majority vote found to be satisfactory. ______________________________ Dr. Tanya Nolan, EdD Chair, School of Radiologic Sciences ______________________________ Chris Steelman, MS Director of MSRS Cardiac Specialist ______________________________ Dr. Laurie Coburn, EdD Director of MSRS RA ______________________________ Dr. Robert Walker, PhD Director of MSRS THE WEBER STATE UNIVERSITY GRADUATE SCHOOL RESEARCH AGENDA STUDENT APPROVAL of a thesis submitted by Snober Shoukat Dr. Ashwini Pardiker This thesis has been read by each member of the student research agenda committee and by majority vote found to be satisfactory. Date Dec 19, 2023 ______________________ Dec 19, 2023 ______________________ ____________________________________ Snober Shoukat Snober Shoukat (Dec 19, 2023 12:06 MST) ____________________________________ Dr. Ashwini Pardiker Table of contents Chapter 1. Introduction ............................................................................................................ 4 Background ........................................................................................................................... 4 Statement of the Problem ...................................................................................................... 5 Purpose of the Study: ............................................................................................................ 6 Research Questions ............................................................................................................... 7 Nature of the Study ............................................................................................................... 8 Significance of the Study ..................................................................................................... 10 Definition of Key Terms...................................................................................................... 10 Summary ............................................................................................................................. 11 Chapter 2: Clinical Background ............................................................................................. 12 Introduction ......................................................................................................................... 12 Etiology .............................................................................................................................. 14 Epidemiology ...................................................................................................................... 16 Pathophysiology .................................................................................................................. 17 History and Physical ............................................................................................................ 18 Evaluation ........................................................................................................................... 19 Treatment/ Management Options ......................................................................................... 21 MEDICAL MANAGEMENT FOR AORTIC STENOSIS ............................................. 21 SURGICAL MANAGEMENT FOR AORTIC STENOSIS ........................................... 21 TRANSCATHETER AORTIC VALVE REPLACEMENT ........................................... 22 BALLOON AORTIC VALVULOPLASTY .................................................................. 23 Complications ..................................................................................................................... 24 Summary ............................................................................................................................. 26 Chapter 3: Literature Reviews ............................................................................................... 28 Documentation. ................................................................................................................... 28 General literature review ..................................................................................................... 28 Clinical Evidence .......................................................................................................... 28 Risks and Benefits ......................................................................................................... 30 Summary ............................................................................................................................. 31 Case Study Literature review ............................................................................................... 31 Themes/Subtopics ............................................................................................................... 32 Summary ............................................................................................................................. 34 Chapter 4: Research Method .................................................................................................. 35 Background ......................................................................................................................... 35 Statement of the Problem .................................................................................................... 36 Purpose of the Study: .......................................................................................................... 37 Research Questions ....................................................................................................... 37 Research Method and Design .............................................................................................. 38 Population ........................................................................................................................... 38 Sample ................................................................................................................................ 39 Data Collection, Processing, and Analysis ........................................................................... 39 Assumptions ........................................................................................................................ 40 LIMITATIONS ................................................................................................................... 41 DELIMITATIONS: ............................................................................................................. 41 SUMMARY: ....................................................................................................................... 42 Chapter 5: Findings ……………………………………………………………………………..43 Findings……………………………………………………………………………………… ………43 Chapter 6: Conclusion……………………………………………………………………………52 Implications…………………………………………………………………………………… ……52 Conclusion…………………………………………………………………………………… …….53 Recommendation……………………………………………………………………………… ….55 Chapter 7: Abstract……………………………………………………………………………..58 References: .............................................................................................................................. 60 Appendices .............................................................................................................................. 63 APPENDIX A: TAVR BIOPROSTHETIC DEVICE IN SITU LOCATION ...................... 63 APPENDIX B: EDWARD LIFESCIENCES BIOPROSTHETIC DEVICE ........................ 64 APPENDIX C: MEDTRONICS COREVALVE EVOLUT R BIOPROSTHETIC DEVICE ................................................................................................................................................. 65 Chapter 1. Introduction Transcatheter Aortic Valve Replacement (TAVR) was first performed in 2002 in a patient who was not fit for surgical replacement of the Aortic Valve 1. It was approved in 2011 for the treatment of Aortic Stenosis. Since then, it has revolutionized the treatment for Aortic stenosis with rapid development and evolution of various bioprosthetic valves. 400,000 patients have undergone TAVR since its approval until 20232. With increasing operator experience and technological advancements, success rates of TAVR are on rise and it has evolved as a primary treatment for Aortic Stenosis. Background TAVR has emerged as an effective minimally invasive treatment modality for elderly with high to moderate risk for surgical replacement of the valve. However, it should be accompanied with careful patient selection following the guidelines to guarantee the safety of the procedure. Increasing technology led to the development of various designs of prosthetic valves, many addressing the complications commonly seen with the long-term outcome. With multiple options available, it is important to have guidelines in valve selection based on patient status, operator experience, associated comorbidities, facility, and available patient care in collaboration with different healthcare departments during pre- and postprocedural monitoring. Statement of the Problem With increasing technology in healthcare and availability of various prosthetic valves for TAVR, there is a necessity to compile the available data to compare the features, benefits and risks associated with each of them. With this data, guidelines can be formed for device selection, based on age, anatomical considerations in the patient, other associated cardiac pathologies, anticoagulation therapy requirement, patient comorbidities, post-procedural follow up requirement. Availability of these guidelines would help in making the right choice of approach, diagnostic workup and patient preparation and follow-up for TAVR especially in octa-, nonagenarians. This study thus aims to improve outcomes of TAVR, especially in elderly population in whom there is an increased incidence of age related degenerative Aortic stenosis. Though there are many individual case studies on TAVR and review analysis 3 of various prosthetic devices, we identified the need for compiling numerous benefits and complications of available devices in association with success of TAVR. With the Edward Sapien 3 valve used in most case studies, there are also few case studies which chose Evolut R and other options available. With this study, we try to put together several factors that led to selection of these devices and their outcomes. It also analyzes anticoagulant therapy at various periods during post-procedural follow up in the available case studies to identify its relation with restenosis as only few of such review studies are available presently. The need for such compilation and guideline creation is because of increasing use of TAVR technology with an increasing number of nonagenarians and older individuals with Aortic Stenosis. This is attributed to increased health-care available in the current age leading to increased life-expectancy of the population. This also necessitates the effect of comorbidities on the success of TAVR and thus case studies related to various pathologies associated with Aortic Stenosis are also considered. Purpose of the Study: The purpose of this qualitative study is to review various prosthetic valves available globally for TAVR and identify their efficacy and drawbacks in relation to patient factors to form guidelines for prosthetic selection among the various available options. It also tries to identify the choice of prosthetic used in various access sites for the TAVR other than the classic femoral approach. It includes data available from various countries, available online in English, to be compiled and categorized. It is further analyzed according to themes formed. Prosthetics like Medtronic’s Evolut R, Edward Sapien 3 are used most commonly along with a few others. These devices are compared in terms of access site used, technical ease during deployment, post-procedural functional assessment like valvular leak, restenosis, follow-up required, and other comorbidities. Case studies available from various countries are analyzed and categorized according to critical factors affecting the outcomes. Research Questions 1. Does prosthetic selection affect the long-term outcomes in TAVR? 2. What is the most preferred prosthetic in the nonagenarian Aortic stenosis population for TAVR? 3. Do vascular malformations and associated vascular comorbidities play a role in device selection? 4. What does valve selection depend on in a patient of Aortic Stenosis with connective tissue disorders like myelodysplastic syndrome? 5. Is there a preferred prosthetic device for valve-in-valve TAVR? This study aims to reinforce the outcomes of TAVR by reducing the number of complications and need for port-procedural continuous diagnostic evaluation thus enhancing the future of TAVR. Nature of the Study This study is a qualitative analysis of the case studies available on TAVR. In addition to simple TAVR, it also includes TAVR associated with vascular malformations, TAVR in patients in nonagenarians, TAVR associated with other valve dysfunctions and other pathologies. It also includes available review literature comparing various prosthetic valve outcomes and efficacy. We have used Google Scholar, PubMed, NCBI, CINAHL and EMBASE to collect available literature on TAVR. We searched for global publications but limited to the data available only in English language and free online availability. There was no limit on the date of publication. The key words used for search include: 1. Case study + TAVR 2. TAVR + anomalous 3. TAVR + abnormal vasculature 4. TAVR + restenosis 5. TAVR + anomalous LCX 6. TAVR + anomalous coronaries 7. TAVR + anomalous right coronary artery 8. TAVR + Connective tissue disorders 9. TAVR + Calcific Aortic stenosis 10. TAVR + Edward Sapien 3 11. TAVR + Evolut R 12. TAVR + Medtronic 13. Self-expandable vs Balloon expandable TAVR 14. valve -in-valve TAVR 15. TAVR bioprosthetic review study A total of 25 case studies and 10 review studies were collected and the data acquired through above mentioned search is systematized to identify patterns and themes. The was concise and categorized for comparison and analysis to identify association between case study outcomes. Interpretation of finding was done using electronic tools for continuous updates and ease of location and sharing of analysis between authors and mentors. Significance of the Study There have been various case studies performed on TAVR associated with coronary vascular anomalies, TAVR in nonagenarians, and other associated rare case scenarios. Also, various review studies and meta-analysis were conducted on the efficacy of various prosthetics used for TAVR. With this study, we try to analyze the outcomes with each prosthetic valve available, study the details of factors in favor and against the long-term outcomes of prosthetics used in anomalous anatomical structures, impact and need of post-procedural anticoagulant therapy depending on comorbid factors in patients. We believe it would help in forming guidelines to increase the success rate and effectiveness of TAVR. Definition of Key Terms 1. TAVR: Transcatheter Aortic Valve Replacement 2. Aortic stenosis: narrowing of aortic valve sufficient to cause cardiovascular symptoms. 3. LCX: Left Circumflex Coronary artery. 4. RCA: Right coronary artery 5. LMCA: Left main Coronary artery. 6. LAD: Left anterior descending artery Summary This research analyzes the globally available case studies on TAVR and does a qualitative analysis of the available data to formulate guidelines in device selection for various patient comorbidities and operator efficiency. Chapter 2: Clinical Background Introduction Aortic stenosis is a valve disease, involving the narrowing of the aortic valve opening. Through the narrowing, it affects the blood flow from the left ventricle to the aorta, which results in high-level pressure in the left atrium.1 The disease is rare in people below the age of 50 years. For the few cases which happen in young people mostly, the disease is a result of birth heart defect where two valves grow instead of the usual three.1 Also, when the valve opening does not grow with the heart, it makes it hard for the heart to pump blood resulting in the thickening of the heart muscles.1 The symptoms of aortic stenosis include shortness of breath, angina pectoris, loss consciousness, cardiac mumble, bulky and heavy heartbeats, and low performance.1 Aortic stenosis is a common valvular disorder leading to left ventricular outflow obstruction.1 Transcatheter Aortic Valve Replacement (TAVR) is a minimally invasive procedure used to replace a diseased aortic valve in the heart. Aortic stenosis, the most common cause of TAVR, occurs when the aortic valve becomes narrowed, reducing blood flow from the heart to the rest of the body. This condition can lead to symptoms such as chest pain, shortness of breath, and fainting, and it can also increase the risk of heart failure.1 Traditionally, aortic valve replacement requires open-heart surgery, which involves making an incision in the chest and stopping the heart to replace the valve. However, TAVR offers a less invasive alternative to surgery, and it has become a widely accepted treatment option for high-risk or inoperable patients.1,5 During TAVR, a new valve is inserted into the heart via a catheter that is guided through a small incision in the patient's groin or chest. The new valve is typically made of bovine material, such as animal tissue, and it is compressed to fit into the catheter. Once the catheter is in place, the valve is expanded and secured in the heart, replacing the diseased valve, and restoring proper blood flow. Patients should consult with their healthcare provider to determine if TAVR is the right treatment option for them.TAVR has several advantages over traditional open-heart surgery, including a shorter hospital stay, less pain, and a faster recovery time.1,5 Additionally, TAVR can be performed under local anesthesia, avoiding the risks associated with general anesthesia. For high-risk or inoperable patients, TAVR can be a lifesaving procedure that improves their quality of life and prolongs their lifespan. However, TAVR is not without risks, and complications can occur, such as bleeding, infection, stroke, and damage to the heart or blood vessels. As with any medical procedure, Etiology The etiology of Transcatheter Aortic Valve Replacement (TAVR) is generally a result of aortic stenosis, a narrowing of the aortic valve that impairs the flow of blood from the heart to the rest of the body. 5 This condition can be caused by a variety of factors, including age-related wear and tear, endocarditis (an infection of the heart valves), or inherited genetic conditions. 1,5 Patients with severe aortic stenosis, a disease in which the aortic valve does not open correctly and reduces blood flow to the body, are frequently candidates for transcatheter aortic valve replacement (TAVR). The most common cause of aortic stenosis is the calcification of the aortic valve, which can occur as a result of aging, rheumatic fever, or congenital heart disease.5 Calcification causes the valve to narrow, reducing blood flow from the heart to the rest of the body and leading to symptoms such as chest pain, shortness of breath, and fainting. 5 The aortic valve's deterioration with age, calcium buildup, and congenital cardiac abnormalities are the main causes of this disorder.5 These elements cause the aortic valve to narrow, which limits the volume of blood that can pass through the valve and reach the body. The aortic valve's age-related wear and tear, calcium buildup, and congenital cardiac anomalies are only a few of the causes of this disorder. 5 Several causes cause the aortic valve to close improperly, which increases the flow of blood back into the aorta.5 Fibrosis is another leading cause of Aortic Stenosis in addition to calcification. Another risk factor for the development of Aortic Stenosis is Bicuspid Aortic Valve. A normal aortic valve has three valves, fewer cusps causes increased wear and tear on each cusp, leading to fibrosis and calcification and eventually Aortic Stenosis. Another condition co-existing with Aortic stenosis is Mitral Stenosis. Such co-existing other valvular conditions and fusion of commissures of the aortic valve differentiates rheumatic etiology from age-related wear and tear. Alkaptonuria, Systemic Lupus Erythematosus, Radiation, Ochronosis, metabolic diseases like Fabry’s disease also cause commissural fusion and development of Aortic stenosis. Supravalvular Aortic Stenosis is seen with William’s syndrome, which is a congenital cardiac defect 3. Epidemiology A large difference in the incidence of Aortic Stenosis is seen between low-income and high-income countries. Rheumatic cause is seen mostly in low-income populations. Whereas, age-related etiology is common in developed nations. Aortic stenosis is becoming more common, especially in aged people. 1,5 It is the 2nd most common valvular pathology in the USA. Aortic stenosis is more common in people over 65 years old, affecting 2-7% of this age group and 3.4% in the population above 75 years of age4. Its prevalence increases with age. Thus, the incidence is expected to increase twofold to threefold within the next decade due to increasing population. TAVR is often performed in patients over 75 years old. This is probably brought on by the aortic valve's age-related wear and tear as well as the incidence of other cardiovascular diseases such hypertension and coronary artery disease. Bicuspid Aortic valve is seen in 0.5-0.8%4. Additionally, the advancement of TAVR has made it a feasible alternative to open-heart surgery for individuals who might not have been eligible, increasing its applicability to a wider population.1 Pathophysiology Aortic stenosis is a condition where the aortic valve becomes narrow, leading to reduced blood flow from the heart to the rest of the body.1 Aortic stenosis causes the aortic valve to narrow, which increases blood flow resistance and makes the heart work harder to pump blood to the body. 1,5 This can result in symptoms such as chest pain, shortness of breath, and fainting, and in severe cases, heart failure.1 Aortic stenosis causes the aortic valve to narrow, which increases blood flow resistance and makes the heart work harder to pump blood to the body. Insidious onset is seen when the cause is age related, but rheumatic patients present progressively over a few months or years. Pressure builds up in the aorta as a result of the aortic valve narrowing in aortic stenosis and the aortic valve closing improperly in aortic regurgitation, which can result in the symptoms of these disorders. Stenosis of the Aortic Valve results in decrease of LV stroke volume,increase in ejection time(VLET) and thus LV pressure rises(LVEDP). The reduced Stroke Volume results in decrease in pressure in the Aorta. The valvular stenosis acts as an increase in afterload for the LV function, and rise in LVEDP acts as an increase in preload. These two hemodynamic changes lead to increased demand for LV contractile force, resulting in an increase in mass of the Left ventricle and eventually might lead to LV dysfunction and failure. The increased myocardial mass demands for increased oxygen consumption, but due to increased LV Ejection Time, coronary perfusion is decreased. Hence, the symptoms of dysfunction and failure arise in LV myocardium over a period of time. History and Physical The history and physical examination are crucial steps in the diagnosis of aortic stenosis. Chest pain, breathlessness, and dizziness are common symptoms of aortic stenosis in patients.1 A physical examination could identify a heart murmur, which is a noise produced by blood flowing turbulently through a constricted valve. 1 Patients progressively experience an increase in dyspnea, fatigue, and decrease in exercise intolerance.Angina occurs due to combination of increased myocardial mass and oxygen demand but reduced cardiac output and myocardial perfusion. Syncope might be seen if cerebral perfusion is decreased. Later stages show development of pulmonary hypertension and pulmonary effusion due to reflection of increased pressures on the right side of the heart by the left heart. Patients with bicuspid aortic valve stenosis also present with symptoms of Infective endocarditis. In severe Aortic Stenosis, the carotid impulse rises slowly due to increase in LV ejection Time, and hence the peak is delayed. The amplitude of the carotid impulse is also low, and the split in the second heart sound(S2) might be absent or reversed(if AV closes after PV). This characteristic carotid pulse is known as pulsus parvus et tardus. A heart murmur can also be detected during a physical checkup. It is a mid-systolic, ejection murmur which is crescendo-decrescendo in nature and highpitched, heard best at the second right intercostal space and radiating to the neck and carotids6. The murmur becomes softer if LV failure or low stroke volume develops. Evaluation Imaging tests like echocardiography or cardiac catheterization are often used to confirm the diagnosis of aortic stenosis. Echocardiography, a non-invasive imaging technique that uses ultrasound waves to create images of the heart. This technique can be used to measure the size of the aortic valve and the amount of narrowing that is present. These tests can aid in determining the degree of valve narrowing and help to inform treatment choices, such as whether TAVR might be a viable option. Before TAVR, patients undergo imaging studies such as echocardiography, CT, or MRI to determine the severity of aortic stenosis and assess the heart and blood vessels' anatomy. This information helps determine if a patient is a good candidate for TAVR. Echocardiography remains the standard approach method to evaluate and follow-up patients with aortic stenosis and stratify them for surgery. 7 In addition to a physical examination, patients may be subjected to a number of procedures, including echocardiograms, electrocardiograms, and cardiac catheterization, to help confirm the diagnosis of aortic stenosis. A non-invasive test called an echocardiography uses sound waves to evaluate the structure and operation of the heart and forms the gold standard test for aortic stenosis. ECG is used to evaluate the electrical activity of the heart. A small tube is placed into an artery in the arm or leg during a cardiac catheterization, an invasive technique that enables the doctor to examine the heart and aortic valve up close. Cardiac computed tomography (CT) use is expanding in patients with calcific aortic valve disease. It is used when all the non-invasive tests are inconclusive.7 Exercise testing helps in precipitation of symptoms in an asymptomatic patient but should be avoided in a symptomatic patient. CT is informative in cases of calcific Aortic Stenosis and if other non-invasive tests are inconclusive. MRI assesses LV mass and function if Echocardiography cannot readily be interpreted. Another sensitive measure of LV function and prediction of adverse events and mortality is Longitudinal Systolic Strain Imaging6. Treatment/ Management Options MEDICAL MANAGEMENT FOR AORTIC STENOSIS Mild AS can be managed with medication and lifestyle changes. Lifestyle changes include avoidance of Sports and strenuous exercise and maintaining adequate volume status with hydration to avoid hypovolemia which might impact the existing low stroke volume. If the aortic stenosis is caused by degenerative calcification of the valve, statins are given to slow the calcific progression associated with a reduced functional area of valve 7. However, if the cause of AS is endocarditis, infection prophylaxis is suggested. SURGICAL MANAGEMENT FOR AORTIC STENOSIS Follow-up Echocardiography is indicated in asymptomatic patients to monitor LV function and valve area. Indications, 7 for surgical intervention include: 1. Severe AS with symptoms 2. LV systolic dysfunction 3. Bicuspid Aortic valvular disease 4. AS with aortic root aneurysm 5. Asymptomatic patients with mild-moderate AS undergoing CABG Studies show medical therapy does not cause any improvement in symptomatic Aortic Stenosis and surgical valve replacement forms the gold standard treatment modality for AS. Diuretics are used to relieve symptoms and decrease congestion before surgery.8 Valvular replacement is also indicated in asymptomatic patients with abnormal stress test, EF less than 50%, patients undergoing CABG due to coronary disease, mean pressure gradient more than 60 mm Hg across the valve. TRANSCATHETER AORTIC VALVE REPLACEMENT TAVR is recommended in adults with symptomatic aortic stenosis, even if the symptoms are mild9. Transcatheter aortic valve replacement is the main option for treating aortic stenosis. During this treatment, a catheter is used to insert a new prosthetic valve into the aortic valve. The prosthetic valve is deployed when the catheter is run up to the heart and into an artery. This minimally invasive technique usually takes under an hour to complete. This procedure can lead to a shorter hospital stay and faster recovery time than open-heart surgery. TAVR can be performed through transfemoral, transapical, subclavian or sometimes transaortic route. Transfemoral approach is the most preferred route in most centers. There are no studies comparing the risks and benefits and the outcome of the procedure through these routes. SOURCE: HARRISON’S PRINCIPLES OF INTERNAL MEDICINE, 20TH EDITION BALLOON AORTIC VALVULOPLASTY It forms the major treatment for those who present with severe/symptomatic aortic stenosis in the pediatric age group. Due to low efficacy and higher chances of restenosis, it is not a definite treatment modality, but it serves as a bridge between medical management and surgical or transcatheter replacement of the aortic valve10. It can be specifically helpful if the contributing comorbidities to the symptoms of aortic stenosis are not yet diagnosed and if the symptoms can be reversed with balloon valvuloplasty. This can fetch time for detailed work-up of the patient and stabilization before performing TAVR or surgery. Complications Complications of Aortic stenosis include LV failure, due to concentric left ventricular hypertrophy, and Microangiopathic Hemolytic Anemia 11. RBCs are damaged while passing through the narrowed and calcified aortic valve producing various shapes and eventually loss of intact cell membrane. This causes intravascular RBC breakdown and leakage of hemoglobin and eventually severe enough to cause anemia. It further impacts the myocardial oxygen demand and contributes to heart failure and its symptoms. Complications associated with TAVR include stroke, other vascular complications, and the need for a pacemaker. Valvular leaks might develop in the immediate post-procedural period or in the long-term. Though it is mild and asymptomatic, timely follow-up after TAVR is important. Valvular leak and development of regurgitation is associated 3-4% with the newly available prosthetics. While TAVR is associated with lesser kidney injury and atrial fibrillation, surgical valve replacement is associated with lesser vascular complications. TAVR can lead to complications such as bleeding, infection, stroke, damage to the heart or blood vessels or even death. The new valve may also malfunction and require further treatment. Patients need to be closely monitored after the procedure to detect and manage any complications. Atrioventricular block, stroke, and valve embolization are a few possible TAVR complications. A major complication of the surgery that can result in stroke and cause long-term damage is stroke. Electrical impulses from the atria to the ventricles are blocked in a condition known as atrioventricular block, which causes an erratic heartbeat. When the artificial valve is not positioned correctly and is expelled from the aortic valve, a blockage elsewhere in the body results. This is known as valve embolization. Patients undergoing open heart surgery also run the risk of developing infections, blood clots, and heart failure. Bacteria can enter the body through the incision and cause infection, which can cause a number of symptoms like fever and chills. In the blood vessels of the heart, blood clots can develop, causing blockages and reduced blood flow. Patients with aortic stenosis are also at an increased risk for infective endocarditis, particularly patients with the bicuspid aortic valve9. Heart failure is one of the most common complications of aortic stenosis. 9 Most patients will have left ventricular hypertrophy with normal systolic function9. Diastolic dysfunction develops secondary to hypertrophy and fibrosis and often persists even after AVR9. However, some patients can present with systolic dysfunction secondary to the afterload mismatch, resulting in a low ejection fraction9. Complications to TAVR include conduction disturbances and the need for a permanent pacemaker, stroke, paravalvular leak, vascular site complications, bleeding, annular rupture, left ventricular perforation, cardiac tamponade, need for surgery, acute myocardial infarction, acute kidney injury, infection, hypotension, and death12. A recent meta-analysis revealed statistically significant evidence of lower rates of both acute kidney injury and major bleeding, and a non-statistically significant trend favoring TAVR over SAVR on overall mortality and stroke 13. Summary TAVR has revolutionized the treatment of aortic stenosis, providing a less invasive and less risky alternative to traditional open-heart surgery. It has become an accepted treatment option for high-risk or inoperable patients, and it has the potential to improve patient outcomes and prolong their lifespan. TAVR has several advantages over traditional surgery, including a shorter hospital stay, less pain, and a faster recovery time. It is also a less invasive procedure that can be performed under local anesthesia, avoiding the risks associated with general anesthesia. However, TAVR is not without risks, and patients must be closely monitored following the procedure to identify and manage any potential complications. Bleeding, infection, stroke, and damage to the heart or blood vessels are all potential complications that can occur following TAVR. The success of TAVR depends on proper patient selection and careful monitoring of patients following the procedure. Patients must undergo various imaging studies to determine the severity of aortic stenosis and assess the anatomy of the heart and blood vessels to determine if they are good candidates for the procedure. Despite the potential risks associated with TAVR, it has become a widely accepted treatment option for high-risk or inoperable patients, offering hope for those who would otherwise have limited treatment options. As technology advances and more research is conducted, TAVR is expected to continue to improve, offering even more benefits and potentially expanding to a wider range of patients. Overall, TAVR represents a significant advancement in the treatment of aortic stenosis, providing patients with a less risky and less invasive alternative to traditional surgery. While careful patient selection and post-procedural monitoring are essential, TAVR has the potential to significantly improve patient outcomes and prolong their lifespan. Chapter 3: Literature Reviews Documentation We used University’s online library OneSearch, Google Scholar and PubMed sources to search for peer reviewed articles. The key words mentioned earlier were used to search. Strategy used for this research is to study available case studies on TAVR with focus on cases that went beyond the practice of an uncomplicated TAVR in a healthy adult. Along with case studies, various review studies on bioprosthetic devices were reviewed to understand technical and design features which would have an impact on the patient outcome and efficiency of TAVR. General literature review Transcatheter Aortic Valve Replacement (TAVR) is an innovative approach to the treatment of aortic stenosis (AS), which is a narrowing of the aortic valve. This procedure is used to replace the aortic valve without the need for traditional open-heart surgery. This procedure has been used in many clinical studies and is indicated for patients with severe symptomatic aortic stenosis who are considered at high risk for conventional open-heart surgery. This literature review will discuss the current clinical evidence on the safety and efficacy of TAVR, as well as the potential risks and benefits associated with the procedure. Clinical Evidence An extensive amount of clinical evidence has been published regarding the safety and efficacy of TAVR. Several randomized controlled trials have compared TAVR to surgical aortic valve replacement (SAVR) in patients with severe symptomatic aortic stenosis.11 The PARTNER trial, which was the first randomized trial to compare TAVR to SAVR, found that TAVR was associated with similar rates of all-cause mortality and stroke as SAVR at one year. 14 Furthermore, TAVR was found to be associated with similar rates of all-cause mortality and stroke as SAVR at three years, although SAVR was associated with a lower rate of rehospitalization for heart failure at three years. In addition, the PARTNER II trial found that TAVR was associated with lower rates of all-cause mortality, stroke, and major bleeding at three years compared to SAVR. 14 The NOTION trial compared TAVR to SAVR in patients who were considered to be at intermediate risk for open-heart surgery and found that TAVR was associated with similar rates of all-cause mortality, stroke, and major bleeding at one year. The NOTION II trial also found that TAVR was associated with similar rates of all-cause mortality, stroke, and major bleeding at three years compared to SAVR. Furthermore, the SURTAVI trial found that TAVR was associated with lower rates of all-cause mortality, stroke, and major bleeding at three years compared to SAVR.14 In addition to the randomized controlled trials, there have also been a number of observational studies that have examined the safety and efficacy of TAVR.13 The PARTNER 3 trial found that TAVR was associated with a lower rate of all-cause mortality at one year compared to SAVR. The Core Valve US Pivotal trial found that TAVR was associated with lower rates of all-cause mortality, stroke, and major bleeding at one year compared to SAVR. The French nationwide registry found that TAVR was associated with similar rates of all-cause mortality and stroke at three years compared to SAVR. Risks and Benefits TAVR is associated with a number of potential risks and benefits. The most common risks associated with TAVR include vascular complications, bleeding, stroke, and death. However, these risks are generally considered to be low, and most patients are able to tolerate the procedure well. The benefits of TAVR include a reduction in the symptoms of aortic stenosis, a reduction in the need for open-heart surgery, and a reduction in the risk of death. Furthermore, TAVR is associated with a shorter recovery time than open-heart surgery and is considered to be a safe and effective treatment for aortic stenosis. Summary TAVR is an innovative approach to the treatment of aortic stenosis that has been studied extensively in clinical trials and observational studies. The evidence suggests that TAVR is associated with similar rates of all-cause mortality, stroke, and major bleeding as SAVR at one and three years. Furthermore, TAVR is associated with a number of potential risks and benefits, including a reduction in the symptoms of aortic stenosis, a reduction in the need for open-heart surgery, and a reduction in the risk of death. Overall, TAVR is considered to be a safe and effective treatment for aortic stenosis. Case Study Literature review Case studies for this review study are sourced online, which are peer reviewed, and in English language. Case studies published in various countries across the world are collected to reduce regional bias, include all the available Bioprosthetic Valves, and review their efficacy in population groups of various ethnicities and races. 25 case studies were collected which were published in the last 25 years. In addition to these another 10 studies comparing various bioprosthetic valves available for TAVR. These studies were compared. a. self-expandable vs Balloon-expandable prosthetics b. Risk of thrombosis during post-procedural follow up with each valve. c. coronary vascular obstruction during the procedure using each valve. d. TAVR with Vi-TAVR with various prosthetic valves. The case studies collected were found to be predominant in the population over 70 years of age. The incidence of Aortic Stenosis increases with age and surgical risk is high in this population group thus making TAVR a preferred method of intervention. Among coexisting cardiac disorders, vascular malformations play a vital role during the TAVR procedure to maintain coronary flow, and reduce complications of MI, arrhythmias to name a few. Another comorbidity impacting TAVR is pathologies in other cardiac valves in addition to Aortic valves. A coexisting prosthetic valve along with Aortic prosthetic valve might interfere with its functioning and resulting in complications. Themes/Subtopics The collected case studies are distributed among the following themes. 1. TAVR in Nonagenarians with degenerative Aortic Stenosis Life expectancy rise in the US population has led to people over 90 years of age increasing from 2.8% to 4.7% since 1980 and is expected to rise to 10% of the total population of the US15. TAVR thus becomes the primary mode of treatment for age related degenerative Aortic stenosis. Hence, this study aims to review the efficiency of various prosthetic devices in this age group. 2. Coronary vascular malformations in TAVR During TAVR, chances of ostial block and coronary flow interruption occur. If right coronary artery flow is disturbed, the patient might deteriorate due to precipitation of arrhythmia. Postprocedural state of the Aortic prosthetic valve is also critical in maintaining coronary flow due to its proximity with both the ostia in the aortic root. Pre-existing vascular malformations increase the incidence of above-mentioned disturbances leading to MI and restenosis of the valve. Thus, consideration of factors playing a role in prosthetic selection for vascular malformations is important for this review. 3. Bicuspid Aortic valve A bicuspid aortic valve is morphologically and histologically different from a normal aortic valve with three semilunar cusps. Hence, studying prosthetic characteristics that are in and out of favor of implanting in a native bicuspid aortic valve needs a mention in this study. 4. Restenosis after TAVR Restenosis of TAVR indicates procedural failure and thus factors impacting restenosis in both the patient and the prosthetic valve require elaborate study. This would help in defining requirements of anticoagulation with each prosthetic valve and would help in choosing the right valve for specific patient status. 5. TAVR vs VI-TAVR Performing TAVR in an existing valve requires special considerations regarding procedural technique and selection of valve. Detailed work in this field would help in improving outcomes of valve-in-valve TAVR. Summary Though there are many case studies and review studies on TAVR along with various comparative analysis of available valves, there is a need for collaborating valve features with patient characteristics to improve the outcomes of TAVR along with patient safety. This study tries to bridge this void in the available literature on TAVR and thus contributing to improvement in patient care in the cardiac catheterization lab. Chapter 4: Research Method Transcatheter Aortic Valve Replacement (TAVR) was first performed in 2002 in a patient who was not fit for surgical replacement of the Aortic Valve 16. It was approved in 2011 for the treatment of Aortic Stenosis. Since then it has revolutionized the treatment for Aortic stenosis with rapid development and evolution of various bioprosthetic valves. 276,000 patients have undergone TAVR since its approval until 202017. With increasing operator experience and technological advancements, success rates of TAVR are on rise and it has evolved as a primary treatment for Aortic Stenosis. Background TAVR has emerged as an effective minimally-invasive treatment modality for elderly with high to moderate risk for surgical replacement of the valve. However, it should be accompanied with careful patient selection following the guidelines to guarantee the safety of the procedure. Increasing technology led to development of various designs of the prosthetic valve, many addressing the complications commonly seen with the long-term outcome. With multiple options available, it is important to have guidelines in valve selection based on patient status, operator experience, associated comorbidities, facility and available patient care in collaboration with different healthcare departments during pre- and postprocedural monitoring. Statement of the Problem With increasing technology in healthcare and availability of various prosthetic valves for TAVR, there is a necessity to compile the available data to compare and contrast the features, benefits and risks associated with each of them. With this data, guidelines can be formed for device selection, based on age, anatomical considerations in the patient, other associated cardiac pathologies, anticoagulation therapy requirement, patient comorbidities, post-procedural followup requirement. Availability of these guidelines would help in making the right choice of approach, diagnostic workup and patient preparation and follow-up for TAVR specially in octa-, nonagenarians. This study thus aims to improve outcomes of TAVR, especially in elderly population in whom there is an increased incidence of age related degenerative Aortic stenosis. Purpose of the Study: The purpose of this study includes reviewing the available prosthetics for TAVR, identifying their efficacy and complications associated with specific patient comorbidities, and to form guidelines for valve selection in TAVR. Prosthetics like Medtronic’s Evolut R, Edward Sapien 3 are used most commonly along with few others. These devices are compared in terms of access site used, technical ease during deployment, post-procedural functional assessment like valvular leak, restenosis, follow-up required, and other comorbidities. Case studies available from various countries are analyzed and categorized according to critical factors affecting the outcomes. Research Questions Q1. Does prosthetic selection affect the long-term outcomes in nonagenarian TAVR? Q2. Do vascular malformations and associated vascular comorbidities play a role in device selection? Q3. Is there a preferred prosthetic device for valve-in-valve TAVR? This study aims to reinforce the outcomes of TAVR by reducing the number of complications and need for port-procedural continuous diagnostic evaluation thus enhancing the future of TAVR. Research Method and Design This study is a retrospective qualitative analysis with exploratory research design. Available case studies on TAVR are collected for case study review, categorized into themes to draw conclusions on the outcomes associated with available prosthetic valves for TAVR. Case studies on TAVR have been published since the introduction of TAVR. Thus, compilation of these case studies and their analysis would be the right choice of literature for this study. Population Data for this study has been collected from case studies published globally, and a total of 25 case studies have been analyzed. Aortic stenosis is diagnosed either in childhood (congenital causes) or in elderly (age-related causes). Due to the high surgical risks in this age group, surgical replacement of aortic valves is not preferred. Thus, Transcatheter Aortic valve Replacement is usually performed in young and elderly patients. In relation to this epidemiological data, case studies have been selected according to a significant number of case studies (15 out of 25) in patients above 75 years of age. Few case studies in teenagers and young patients are also studies to understand the outcomes in patients of congenital heart diseases. Increasing numbers of people are living in their 8th and 9th decades of life because of improved healthcare, thus significant attention was given to case studies in this population. Sample A total of 25 case studies from various countries, ethnicities and population range was collected for this retrospective qualitative analysis. Case studies were selected based on associated 1. cardiac pathologies like vascular malformations, coexisting multiple valvular disease, Aortic pathology 2. connective tissue disorders 3. Prosthetic Valve restenosis 4. Selection of access site other than femoral approach. Stratifying the case studies under these themes would help understand the factors that lead to specific Prosthetic selection and occurrence of post-procedural complications. Thus, analyzing the data and formulating the guidelines would be easier with improved outcomes for the study. Data Collection, Processing, and Analysis Data for this case study review was collected from online resources for published case studies like PubMed, Google Scholar, University library databases, NCBI, CINAHL and EMBASE. The collected data is then categorized into age groups, each with a 10-years range. Special attention was given to those above 80 years of age. Need for pre-procedural analysis, need for predilatation during valve deployment, occurrence of complications like MI, Arrhythmias were studied in this age group to analyze the procedural risk and long-term benefits associated with various prosthetics. The study was assessed and improved on a continual basis by both the researchers as and when newer information was found. Review studies comparing self-expanding with balloon expandable prosthetic valves were also collected to understand the features and technical details of valve function and deployment. Collection of case studies was continued until enough population range and anomalies were covered. Assumptions Data in this study was collected mostly from the population above 70 years of age, thus the majority of the study sample consists of people in their 8th and 9th decades of life. This was done with the assumption that most of the TAVRs are done in elderly population. Another assumption made during this case study is, data was obtained only from online resources, in English language and only those case studies that were available free of charge assuming all significant and relevant information was collected. Though other available prosthetic valves were included, attention was given to Medtronic’s Core valve, Evolut R and Edward Lifesciences, Sapien # valve assuming these are used most commonly in healthcare systems across the world. LIMITATIONS 1. The case studies are reviewed retrospectively. Hence, there is no way of sourcing any missing information in the case study. To avoid variations, only case studies are selected which have the information needed for the review. 2. The outcomes of TAVR were followed up for varied duration in each case study. For correct analysis and comparison, all the outcomes are considered until 1 year follow-up. 3. The study mostly includes TAVRs in patients with other comorbidities, anatomical and functional cardiac pathologies. Thus, the results might not be applicable to a straightforward TAVR performed in a healthy young adult. DELIMITATIONS: Delimitations of this study include: The literature reviewed for this study includes case studies available on the website and in the English language. The case studies reviewed are peer reviewed publications in the last 25 years. The case studies published until February 2023 are included in this case study review. The case study focuses more on the TAVR prosthetics- Evolut R and Sapien 3. Other regionally available prosthetics were not included due to the lack of proven efficiency. Effectiveness is considered based on the patient status for the time period mentioned in each case study. Loss of patient to follow-up and unknown deaths are out of the scope of this study and are not considered during review and analysis. SUMMARY: The project is an overall endeavor to enhance TAVR results and lessen the requirement for post-procedural diagnostic monitoring, which may increase patient access to and affordability of the TAVR. The study's methodology includes gathering and examining case studies from a variety of sources, and the researchers anticipate that the results will help to clarify the criteria for choosing and implementing various bioprosthetic valves in TAVR. The study, which is based on a retrospective analysis of case studies from around the globe and largely focuses on patients over 75, who make up the biggest group of TAVR users, is based on a retrospective analysis of case studies. To create guidelines that would increase the effectiveness and safety of TAVR for elderly patients, the researchers set out to determine the variables that affect prosthetic selection and post-procedural results. Studies show that the Edward Sapiens 3 and Edward R Prosthesis from Medtronic are among the frequently utilized devices. To make inferences about the results with regards to the prosthetic valves that are now accessible for TAVR, the access site chosen, technical simplicity during placement, post procedural functional assessments like valvular leak, restenosis, follow-up need, and other comorbidities are compared across these devices. The study makes the assumptions that the majority of TAVRs are performed on older patients, and that only case studies that were freely available online and in the English Language were used to collect data. The study focuses more on the TAVR prosthetics Evolut R and Sapien 3 and uses case studies that have been published up until February 2023. The study's delimitations include: the literature review for this study included case studies available online and in the English language only. The case studies reviewed are peer-reviewed publications from the last 25 years. The fact that the case studies are being assessed retrospectively and that the results of TAVR were followed up for different amounts of time in each case study are two possible risks to validity. Case studies that analyze results up to a year of follow-up are taken into consideration to prevent variances. Furthermore, because the majority of the study's TAVR patients had additional comorbidities, structural or functional cardiac abnormalities, the findings might not apply to a basic TAVR carried out on a reasonably healthy young adult. The goal of the study is to contribute to available information to improve the results of TAVR by lowering the incidence of procedural problems and ease postprocedural diagnostic assessment. The study aims to improve outcomes for the elderly population, which has an increased incidence of age-related degenerative aortic stenosis, by reviewing the prosthetics that are currently available for TAVR, identifying their efficacy and complications associated with particular patient comorbidities, and formulating guidelines for valve selection in TAVR. Chapter 5: Findings Our purpose through this study is to review the available literature on TAVR, analyze various case studies describing unusual scenarios to provide comprehensive information summarizing the essential components to learn as a cardiovascular invasive specialist, while assisting a TAVR procedure in the cath lab. As most of the existing literature is focussed on physician’s point-of-view and not directed towards the other staff members we believe it will be a helpful source for someone interested in learning requirements of a cath lab assist during a TAVR procedure as an efficient team member. We have categorized the twenty five case studies based on the themes mentioned earlier, so that we could analyze and find answers to the questions formulated at the beginning of this thesis. Once these questions are answered, it will be easier to prove/disprove the hypothesis. Results: Of the twenty five case studies, the majority of the patients were aged from 60 years to 90 years, with 10 patients between 70-79 years. Of the 5 patients aged above 79 years, 4 of them either required additional hemodynamic support measures or required additional intervention before or after valve deployment. An 82 year old patient, with H/o DM and A. Fibrillation developed delayed coronary obstruction(DCO) at 15 months post-TAVR. Coronary obstruction is usually common around 7 days post-procedure, but this is a rare incident happening due to native valve calcification obstructing the left coronary ostium. Low height of the left coronary sinus and long length of the cusp are identified as risk factors for ostial occlusion due to native valve calcification, which can be prevented by low implantation, chimney stenting and continuous follow-up up to 1 year with examination, CT, angiography as required. In concordance with the above findings, chimney stenting was performed in 3 patients(aged 75 and above) along with TAVR as a preventive measure. No post- procedural complications were noticed and the follow-up visits showed normal improvement in the cardiac and hemodynamic status of the patient. An 88 year old patient could recover without any complications during and after TAVR, which was performed along with a percutaneous intervention in left main and left anterior descending artery because of the use of ECMO as a preventive measure. Another patient, though young at 57 years of age, with the Left circumflex artery arising from right cusp, thus making it a right dominant heart, along with critical aortic stenosis was provided mechanical cardiac support before performing TAVR. The patient had an uneventful procedure and recovery. It suggests the benefits of utilizing preventive support measures in octa- and nonagenarian frail patients or patients with compromised hemodynamic status before the procedure. An interesting finding during the post-procedural recovery of a TAVR patient is the significance of dual antiplatelet therapy. A 77 year patient underwent uncomplicated TAVR with a Sapien 3 valve. At 1 year follow-up, showed increased gradient across the valve(48 mm Hg) and thickened TAVR leaflets on imaging. Further exploration revealed non-adherence to anticoagulants, which is a significant factor of failure of the prosthetic valve. Treatment with an aggressive non-Vitamin-K antagonist for 3 months revealed a decrease in the gradient to 17 mm Hg and improvement in the functional status of the patient. In relation to existing comorbidities in the patient affecting TAVR outcomes, an interesting finding is the effect of End-Stage Renal disease. A 62 year patient with a previous stent in the left main coronary artery and surgical aortic valve replacement developed sudden onset chest pain and breathlessness. Upon examination it is revealed that the Accurate Neo surgical prosthetic device has been occluded due to calcification resulting from ESRD. The LVEF is reduced to 38%, with aortic valve gradient of 74 mmHg and the valve area is only 0.61 mm2. An emergent TAVR was performed with a Sapien 3 device along with the balloon inflation in the LAD to prevent stent dislodgement. Calcified lesions require deployment with higher inflation pressures, which might dislodge the existing stents near ostial or left main arteries. Hence support with balloon inflation prevents intraprocedural complications and deterioration of the patient. Out of 3 patients with bicuspid aortic valve, one patient was treated with corevalve Evolut R. Five months after implantation, the patient developed severe cardiac arrest and ventricular fibrillation. After CPR and 2 shocks, ROSC was established and the patient was analyzed in CCU. Coronary angiography 9 months before TAVR showed diffuse lesion in left main and LAD arteries which were not intervened. Hence, the decision to perform PCI was taken. The nitinol frame of the CoreValve caused difficulties in engagement of the left and right coronaries and required a 7F guide extension support for coaxial engagement of imaging and interventional catheters into the coronaries. A bicuspid aortic valve requires a high deployment thus increasing the chances of sealing the coronary ostia by the skirting of the valve. Using a CoreValve causes further difficulties in future coronary interventions due to obstruction given by the frame of the valve. Hence, balloon expandable valves like Sapien 3 are preferred in patients with bicuspid AV with regards to expecting a future PCI in the coronaries. The other two patients with bicuspid AV treated with Sapien 3 valve showed intra or post procedural complications. A unicuspid AV requires the use of Sapien 3 valve as it provides a good support with the skirting and low deployment. As there is a chance of coronary occlusion, flow needs to be checked before and after valve deployment and also during the follow-up period. In addition, funneling of the LVOT and irregularity in annulus might not favor low implantation of the Sapien valve, requiring surgical implantation. In addition, as bicuspid AV is commonly associated with vascular anomalies, specially critical ones in which the course of the anomalous vessels in interarterial ( for example, between PA and ascending aorta), use of balloon expandable mandates coronary artery protection with preventive intervention or continuous follow-up postprocedure to ensure there is no significant coronary occlusion. Hence, it is very critical to choose a compatible device in patients with both bicuspid Av and critical anomalous coronary vasculature and the decision is based on individual case-by-case evaluation with close follow-up for extended periods utilizing various imaging methods. An important consideration required during a TAVR is a previous mitral valve replacement. The presence of a prosthetic mitral valve increases the susceptibility of the embolization of the TAVR prosthetic valve while deployment due to watermelon seed effect. Hence, surgical implantation is recommended in such patients. A case reported 2 failed attempts of retrieving and deployment of the valve, hence converting into a surgical implantation for successful completion of the procedure. The age of the patient was 79 years, and two events of embolization could have provided severe risk of injury to various structures around the aortic root and ascending aorta. Hence, these factors need to be considered while taking the primary decision of TAVR. Summary: Our research aims to provide a comprehensive review of the literature on TAVR concentrating on case studies which highlights unique scenarios. The goal is to provide essential insights for cardiovascular invasive specialists involved in TAVR procedures in the Cath lab highlighting the viewpoint of non physician staff. The research categorizes 25 case studies based on themes, addressing key questions established in the thesis introduction. Among the significant findings, the majority of TAVR patients were between 60 and 90 years old, giving special consideration to the patients above 79 years who needed additional hemodynamic assistance. Uncommon occurrences, such as delayed coronary obstruction were explored emphasizing risk factors and preventive measures. The Chimney Stenting was proved effective in preventing complications in elderly patients, promoting the idea of utilizing preventive measures in fragile individuals. The study emphasizes the significance of dual antiplatelet therapy after TAVR highlighting a scenario where non adherence resulted in valve failure, this was later treated through intensive treatment with non-Vitamin K antagonist treatment. End stage renal disease on the outcomes of TAVR showcasing the importance of prompt interventions and preventive measures. In bicuspid aortic valve cases, difficulties in deploying Corevalve were outlined, emphasizing the preference for balloon expandable valves such as Edward Sapian. Issues related to vascular anomalies and coronary artery protection were addressed, emphasizing the importance of careful device selection and close follow up. The study suggests important factors when considering TAVR for the patients with prior mitral valve replacement, highlighting the risk of prosthetic valve embolization during TAVR. Surgical implantation is recommended in TAVR patients with previous mitral valve replacements to avoid potential risks. Overall this study provides valuable insights into TAVR procedures, with a particular focus on unique case studies. It offers recommendations for cardiovascular invasive specialists to enhance procedural success and improve patient outcomes. These findings can guide healthcare professionals in delivering optimal care to TAVR patients and contribute to the ongoing advancement of TAVR procedures. Chapter 6: Implications, Recommendations, and Conclusions. As the healthcare system in the USA is enhancing in multiple folds, it is reflecting a rise in life expectancy and hence the percentage population of elderly people. Aging, being the most common etiology of aortic stenosis, there has been a constant increase in the incidence of the disease and hence the need for TAVR. Though the USA is leading in the number of TAVR procedures performed, there still is the need to establish more facilities performing the procedure. Continuous reviews of the published case studies helps in knowledge improvement and staying updated with the current changes in protocols and device developments. With this intent we aim to provide our findings as a useful informative material for cardiovascular invasive specialists to encourage, guide and support them in assisting physicians for a TAVR procedure. The limitations we faced during this review are related to the retrospective nature of the study, thus limiting the information and inconsistencies in the method of reporting of each case study. We actively worked on not disclosing any information or having any bias in perception while analyzing the case studies. Implications and conclusion: 1. Does prosthetic selection affect the long-term outcomes in TAVR? Though prosthetic selection plays an important role in the outcomes of TAVR, following are the findings indicating various patient factors play a crucial role in developing outcomes. 2. What is the most preferred prosthetic in the nonagenarian Aortic stenosis population for TAVR? EDWARDs SAPIEN III valve is the preferred bioprosthetic in nonagenarians due to its proven efficiency and ease of technique. We found 2 nonagenarian case studies that both used Edward Sapien 3 valves. 3. Do vascular malformations and associated vascular comorbidities play a role in device selection? Yes, anomalous coronary vasculature requires ensuring adequate coronary flow. Hence, the self expandable valve can be recaptured and aligned accordingly. 4. What does valve selection depend on in a patient of Aortic Stenosis with connective tissue disorders like myelodysplastic syndrome? In patients with CTDs, pre-TAVR PCI is not preferred, especially in RCA. Instead CABG is performed followed by TAVR. SAVR is avoided. Hence procedural requirements are more critical than the type of valve used. 5. Is there a preferred prosthetic device for valve-in-valve TAVR? Not yet proven, but Acurate Neo has been used in a few cases of V-iV TAVR. Sizing and plane of deployment is more critical than the type of valve in V-iV TAVR. Recommendations: During our literature review on TAVR cases, we have identified a few case studies addressing variations in the standard TAVR procedure. Case studies addressing LV injury, cardiac tamponade, and conduction abnormalities after rapid pacing are limited to under 10. However, these complications are common and create havoc in the cath lab. Hence, we recommend that all the healthcare personnel working in association with TAVR procedures report and publish cases that appear to have deviated findings from the standard procedure. It can be as simple as managing a symptom with a particular drug or intervention, which helps revive the patient and complete the case successfully. In addition, we identified several patient factors impacting device selection. Hence, it is recommended that the cath lab associate with various companies and use different devices to fit the patient best. Presently, each cath lab associates themselves with only one device manufacturer; even if they are associated with more than one company, there is an inclination towards one over the other. This might cause undesirable effects and increase the morbidity and mortality associated with TAVRs. Highlight the significance of evaluating not just the immediate post-procedural effects but also the extended outcomes, such as the 5year mortality rates associated with particular devices. Highlighting the significance of a comprehensive patient assessment is crucial in identifying the optimal TAVR device and size. This assessment should encompass not just valve morphology and measurements but also account for individual patient factors like age and the potential requirement for future Valve-in-Valve TAVR. The study highlights the importance of not only relying on measurements and valve morphology but also considering patient-related factors. A recommendation to the cath lab staff is to participate in the TAVR and other structural procedures voluntarily. Presently, very few cath lab personnel choose to learn and participate in these procedures because of the complexity and demanding nature of the procedure when compared to catheterization and PCI. Conducting educational workshops and providing added benefits will create interest in the cath lab staff to participate in TAVR, increasing the number of TAVR procedures performed and improving efficiency and success. Educate healthcare professionals on the variety of TAVR devices available, with a focus on the commonly used ones like Edward Lifesciences' Sapien III valve and Medtronic’s CoreValve Evolut R. Encourage ongoing research and consideration of other devices for their efficacy and safety. Promote sustained exploration in the TAVR field and the development of new devices and technologies. Highlight the potential for continuous improvement in procedural techniques and device technology to enhance patient outcomes. Emphasize the increased occurrence of patientprosthesis mismatch, particularly with certain TAVR devices like the Sapien 3 valve. Advocate for heightened awareness among clinicians when choosing devices, considering this factor. Convey the results regarding the assessment of mortality and morbidity linked to various TAVR devices across time. Highlight the significance of evaluating not just the immediate post-procedural effects but also the extended outcomes, such as the 5-year mortality rates associated with particular devices. There is a need to have guidelines for publishing a TAVR case. We have observed that the case studies we collected widely vary in terms of symptomatic details, diagnostic findings, follow-up duration, and imaging provided in each of them. This leads to difficulties during comparative studies, retrospective studies, and meta-analyses. Following guidelines leads to an increased pool of relevant studies to analyze, conclude, and formulate recommendations to increase the procedure's efficiency. Present recommendations for future research. Design some models that predict outcomes by taking into account specific factors unique to each patient, helping in the selection of medical devices. This has the potential to minimize complications and enhance overall outcomes, and investigate strategies for promptly handling complications associated with TAVR, particularly on cardiac tamponade and LV injury. It is very important to educate healthcare professionals on the variety of TAVR devices available, with a focus on the commonly used ones like Edward Lifesciences Sapien III valve and Medtronic’s CoreValve Evolut R. Encourage ongoing research and consideration of other devices for their efficacy and safety. Abstract Background Transcatheter Aortic valve replacement(TAVR) has revolutionized the treatment of Aortic Stenosis with minimally invasive techniques reducing the surgical risk and highly beneficial in patients at high risk for surgery. Various prosthetic devices are available for TAVR. However, reviewing case studies on TAVR using these devices is necessary to understand the beneficiary features of these valves concerning patient characteristics and comorbidities. This study tries to bridge the gap in the literature available on TAVR to contribute to improvement in outcomes of TAVR and the efficiency of cardiac catheterization labs in patient care and safety. Discussion Peer-reviewed case studies in the English language will be collected from various online sources like PubMed, Google Scholar, and the WSU library. In addition, we aim to collect case studies from various countries worldwide to understand the current status of TAVR and to reflect the study outcomes on patients of various races and ethnicities with different etiologies of Aortic Stenosis and beneficial results for cardiac catheterization labs with varied standards of care. These case studies will be reviewed retrospectively and analyzed exploratorily under various themes like age groups of the population, associated vascular malformation, coexisting valvular pathologies, and studies on Valve-In-Valve TAVR. We expect to find a significant amount of literature on the population over 70 due to the increased incidence of Aortic Stenosis in this age group. Therefore, we plan to form limitations and delimitations for the study based on the sample population, follow-up duration, and the amount of literature collected. We aim to find specific patient indications for selecting individual valves over others and formulate clear contraindications for all available valves. There are varied requirements for post-procedural follow-up care with each valve. We expect to analyze the same to minimize patient visits with an improved standard of care in terms of both health and monetarily. Conclusion With an increase in the aging population due to improved healthcare, there is a requirement to study various aspects of TAVR and correlate the bioprosthetic valve features with patient factors. Such studies would help better understand TAVR, making it the gold standard of treatment with adequately laid patient and prosthetic selection guidelines. TAVR has not only reduced the surgical risk associated with traditional aortic valve replacement surgery but has also emerged as a highly beneficial option for patients at high risk for surgical intervention. The availability of various prosthetic devices for TAVR has expanded treatment options, and understanding the variation of these devices is crucial in optimizing patient outcomes. References: 1. Bourantas CV, Serruys PW. Evolution of Transcatheter Aortic Valve Replacement. Circulation Research. 2014;114(6):1037-1051. doi:https://doi.org/10.1161/circresaha.114.302292 https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.114.302292 . 2. Spears J, Al-Saiegh Y, Goldberg D, Manthey S, Goldberg S. TAVR: A Review of Current Practices and Considerations in Low-Risk Patients. Khera S, ed. Journal of Interventional Cardiology. 2020;2020:1-13. doi:https://doi.org/10.1155/2020/2582938 3. Sattar HA. Fundamentals of Pathology : Medical Course and Step 1 Review. Pathoma.com; 2021. 4. Ancona’ R, Pinto’ SC. Epidemiology of aortic valve stenosis (AS) and of aortic valve incompetence (AI): is the prevalence of AS/AI similar in different parts of the world? www.escardio.org. Published February 12, 2020. https://www.escardio.org/Journals/E-Journal-of- Cardiology-Practice/Volume-18/epidemiology-of-aortic-valvestenosis-as-and-of-aortic-valve-incompetence-ai 5. Pujari SH, Agasthi P. Aortic Stenosis. PubMed. Published 2020. https://www.ncbi.nlm.nih.gov/books/NBK557628/ 6. Le T, Bhushan V, Sochat M. First Aid for the USMLE Step 1 2022. Mcgraw-Hill Education; 2022. 7. Pujari SH, Agasthi P. Aortic Stenosis. In: StatPearls StatPearls Publishing; 2023 Jan-. Accessed March 26, 2023. https://www.ncbi.nlm.nih.gov/books/NBK557628/ 8. Wiener C, Fauci AS, Hauser SL, et al. Harrison’s Principles of Internal Medicine Self-Assessment and Board Review, 20th Edition. McGraw Hill Professional; 2021. 9. Sattar HA. Fundamentals of Pathology : Medical Course and Step 1 Review. Pathoma.com; 2021. 10. Pujari SH, Agasthi P. Aortic Stenosis. In: StatPearls StatPearls Publishing; 2023 Jan-. Accessed March 26, 2023. https://www.ncbi.nlm.nih.gov/books/NBK557628/ 11. A John Camm, Lüscher TF, Maurer G, Serruys PW. The ESC Textbook of Cardiovascular Medicine. Oxford Oxford University Press -12-01; 2018. https://oxfordmedicine.com/view/10.1093/med/9780198784906.001.0 001/med-9780198784906-chapter-782 12. Le T, Bhushan V, Sochat M. First Aid for the USMLE Step 1 2022. Mcgraw-Hill Education; 2022. 13. Mahmaljy H, Tawney A, Young M. Transcatheter Aortic Valve Replacement.In: StatPearls StatPearls Publishing; 2023 Jan-. Accessed March 26, 2023. https://www.ncbi.nlm.nih.gov/books/NBK431075/ 14. Kheiri B, Osman M, Bakhit A, et al. Meta-Analysis of Transcatheter Aortic Valve Replacement in Low-Risk Patients. Am J Med. 2020;133(2):e38-e41. doi:10.1016/j.am med.2019.06.020 https://pubmed.ncbi.nlm.nih.gov/31295442/ 15. Office UCBPI. Census Bureau Releases Comprehensive Analysis of Fast-Growing 90-and-Older Population - Aging Population Newsroom - U.S. Census Bureau. www.census.gov. https://www.census.gov/newsroom/releases/archives/aging_populatio n/cb11-194.html 16. Bourantas, Christos V., and Patrick W. Serruys. “Evolution of Transcatheter Aortic Valve Replacement.” Circulation Research, vol. 114, no. 6, 14 Mar. 2014, pp. 1037–1051, https://doi.org/10.1161/circresaha.114.302292. 17. Glenn, Katie. “Report Finds TAVR Is Dominant Form of Aortic Valve Replacement, Outcomes Steadily Improving in the United States.” American College of Cardiology, 16 Nov. 2020, www.acc.org/about-acc/press-releases/2020/11/16/18/53/report-findstavr-is-dominant-form-of-aortic-valve-replacement-outcomessteadily-improving-in-the-us. Appendices Supplementary Files APPENDIX A: TAVR BIOPROSTHETIC DEVICE IN SITU LOCATION Source: dfornell. Edwards Sapien 3 Transcatheter Heart Valve Receives Approval In China. DAIC. Published June 8, 2020. Accessed April 28, 2023. https://www.dicardiology.com/content/edwards-sapien-3-transcatheter-heartvalve-receives-approval-china Source: Transcatheter Aortic Valve Replacement (TAVR) | the Department of Surgery. surgery.arizona.edu. Accessed April 28, 2023. https://surgery.arizona.edu/divisions/cardiothoracic-surgery/services/transcatheter-aorticvalve-replacement-tavr Source: Fillippo TS. TAVR. www.st tammany.health. Accessed April 28, 2023. https://www.sttammany.health/tavr APPENDIX B: EDWARD LIFESCIENCES BIOPROSTHETIC DEVICE Source: dfornell. Sapien 3 TAVR Valve Expanded to Intermediate Risk Patients in Europe. DAIC. Published September 20, 2016. Accessed April 28, 2023. https://www.dicardiology.com/content/sapien-3-tavr-valveexpanded-intermediate-risk-patients-europe APPENDIX C: MEDTRONICS COREVALVE EVOLUT R BIOPROSTHETIC DEVICE Source: dfornell. Canada Clears Medtronic Evolut TAVR for Both Bicuspid Valves and for All Low Risk Patients. DAIC. Published January 11, 2021. Accessed April 28, 2023. https://www.dicardiology.com/content/canada-clearsmedtronic-evolut-tavr-both-bicuspid-valves-and-all-low-risk-patients Snober and Ashwini thesis Final Audit Report Created: 2023-12-19 By: Cathy Wells (cathywells@weber.edu) Status: Signed Transaction ID: CBJCHBCAABAA7kk6mRHztSAkmBt8-KuTvL-1lLNCVrMI 2023-12-19 "Snober and Ashwini thesis" History Document created by Cathy Wells (cathywells@weber.edu) 2023-12-19 - 5:17:26 PM GMT- IP address: 137.190.58.212 Document emailed to snobershoukat@mail.weber.edu for signature 2023-12-19 - 5:18:46 PM GMT Document emailed to ashwinipardiker@mail.weber.edu for signature 2023-12-19 - 5:18:46 PM GMT Email viewed by ashwinipardiker@mail.weber.edu 2023-12-19 - 5:18:53 PM GMT- IP address: 66.249.84.6 Email viewed by snobershoukat@mail.weber.edu 2023-12-19 - 7:02:05 PM GMT- IP address: 74.125.215.169 Signer snobershoukat@mail.weber.edu entered name at signing as Snober Shoukat 2023-12-19 - 7:06:35 PM GMT- IP address: 24.10.249.213 Document e-signed by Snober Shoukat (snobershoukat@mail.weber.edu) Signature Date: 2023-12-19 - 7:06:37 PM GMT - Time Source: server- IP address: 24.10.249.213 Signer ashwinipardiker@mail.weber.edu entered name at signing as DR ASHWINI PARDIKER 2023-12-19 - 7:40:15 PM GMT- IP address: 107.122.173.123 Document e-signed by DR ASHWINI PARDIKER (ashwinipardiker@mail.weber.edu) Signature Date: 2023-12-19 - 7:40:17 PM GMT - Time Source: server- IP address: 107.122.173.123 Agreement completed. 2023-12-19 - 7:40:17 PM GMT