Cerebral Embolic Protection Devices for Transcatheter Aortic Valve Replacement: Review of the Literature and Future Perspectives.

PURPOSE OF REVIEW: Transcatheter aortic valve replacement (TAVR) has been a revolutionary therapy in the treatment of aortic valve stenosis. The risk of stroke associated with TAVR has decreased significantly since its introduction; however, it remains a devastating complication when it does occur. RECENT FINDINGS: Many of the strokes associated with TAVR occur peri-procedurally and are thought to be due to embolic debris entering the cerebrovascular circulation. A number of different cerebral embolic protection devices (CEPD) have been developed and are in various stages of testing and use. The results from clinical trials evaluating the role for CEPD to reduce the risk of stroke have been mixed. As a result, their uptake has been very heterogeneous. This review provides a summary of the diverse CEPD devices available for use and outlines the clinical evidence available to date.

Sex differences in device-measured physical activity after transcatheter aortic valve replacement.

OBJECTIVE: Physical activity (PA) is an important clinical and quality of life outcome after transcatheter aortic valve replacement (TAVR). We examined the effect of TAVR on objectively measured PA in patients with cardiac implanted electronic devices (CIEDs). METHODS: Daily accelerometer data was obtained from CIEDs. Patients in the University of North Carolina Health System with continuous PA data at least 6 months before TAVR and 12 months after TAVR were included. Changes in activity pre- and post-TAVR were analyzed with linear mixed-effects models using a random intercept for each patient. An interaction term was included to determine differences in PA between men and women pre- and post-TAVR. RESULTS: Of the 306 patients with CIEDs who underwent TAVR, 24,655 patient-days of data from 46 patients, mean age of 82 years old, 44% of whom were female met inclusion criteria. A significant and sustained increase of 14.7% in daily PA was seen after TAVR [10.15 minutes per day, 95% confidence interval (CI) 8.75 to 11.56 P < .001] after adjusting for sex, obesity, race, history of depression, and Charlson Comorbidity Index. Effects were more prominent in women (18.57 [95% CI 16.36 to 20.79, P < .001] minute increase post-TAVR) compared to men (4.51 [95% CI 3.87 to 5.16] minute increase post-TAVR, P < .001). CONCLUSIONS: This study demonstrates PA increases after TAVR with effects more pronounced in women than men. Further, this study highlights the potential use of remote monitoring data for monitoring functional outcomes in device patients after a procedure.

Simulating Cardiac Fluid Dynamics in the Human Heart.

Cardiac fluid dynamics fundamentally involves interactions between complex blood flows and the structural deformations of the muscular heart walls and the thin, flexible valve leaflets. There has been longstanding scientific, engineering, and medical interest in creating mathematical models of the heart that capture, explain, and predict these fluid-structure interactions. However, existing computational models that account for interactions among the blood, the actively contracting myocardium, and the cardiac valves are limited in their abilities to predict valve performance, resolve fine-scale flow features, or use realistic descriptions of tissue biomechanics. Here we introduce and benchmark a comprehensive mathematical model of cardiac fluid dynamics in the human heart. A unique feature of our model is that it incorporates biomechanically detailed descriptions of all major cardiac structures that are calibrated using tensile tests of human tissue specimens to reflect the heart's microstructure. Further, it is the first fluid-structure interaction model of the heart that provides anatomically and physiologically detailed representations of all four cardiac valves. We demonstrate that this integrative model generates physiologic dynamics, including realistic pressure-volume loops that automatically capture isovolumetric contraction and relaxation, and predicts fine-scale flow features. None of these outputs are prescribed; instead, they emerge from interactions within our comprehensive description of cardiac physiology. Such models can serve as tools for predicting the impacts of medical devices or clinical interventions. They also can serve as platforms for mechanistic studies of cardiac pathophysiology and dysfunction, including congenital defects, cardiomyopathies, and heart failure, that are difficult or impossible to perform in patients.

A model of fluid-structure and biochemical interactions for applications to subclinical leaflet thrombosis.

Subclinical leaflet thrombosis (SLT) is a potentially serious complication of aortic valve replacement with a bioprosthetic valve in which blood clots form on the replacement valve. SLT is associated with increased risk of transient ischemic attacks and strokes and can progress to clinical leaflet thrombosis. SLT following aortic valve replacement also may be related to subsequent structural valve deterioration, which can impair the durability of the valve replacement. Because of the difficulty in clinical imaging of SLT, models are needed to determine the mechanisms of SLT and could eventually predict which patients will develop SLT. To this end, we develop methods to simulate leaflet thrombosis that combine fluid-structure interaction and a simplified thrombosis model that allows for deposition along the moving leaflets. Additionally, this model can be adapted to model deposition or absorption along other moving boundaries. We present convergence results and quantify the model's ability to realize changes in valve opening and pressures. These new approaches are an important advancement in our tools for modeling thrombosis because they incorporate both adhesion to the surface of the moving leaflets and feedback to the fluid-structure interaction.

Contemporary Trends in Acute Myocardial Infarction in the American Indian/Alaska Native U.S. Population, 2000 to 2018.

Coronary heart disease is disproportionately prevalent in the American Indian/Alaska Native (AI/AN) population. As care for acute myocardial infarction (AMI) continues to advance, equitable distribution and access for the AI/AN population is essential. Primary AMI hospitalizations for adults ≥18 years of age were identified from the Healthcare Cost and Utilization Project National Inpatient Sample from 2000 to 2018. Related co-morbidities, procedures of interest, and in-hospital mortality were also identified. These rates were stratified by race then trended over years using Poisson regression. Overall, 9,904,714 weighted hospitalizations for primary AMI were identified. From 2000 to 2018, AI/AN adults had relatively high rates of primary AMI hospitalization, second only to non-Hispanic (NH) White adults. The AMI rate increased from 14.0/1,000 to 16.1/1,000 among AI/AN adults, remaining higher than NH Black adults (12.1/1,000 to 13.0/1,000) and Hispanic adults (10.3/1,000 and 12.7/1,000) and becoming increasingly closer to NH White adults (25.1/1,000 to 20.0/1,000) (p <0.001 for each). AI/AN adults presented 5 years earlier than their NH White counterparts (64 vs 69 years old; p <0.001). In-hospital mortality was approximately 5% for all race categories and decreased in all groups but decreased at a much greater rate for NH White, NH Black and Hispanic adults (0.2% per year) compared with AI/AN adults (0.08% per year; p <0.001 for each comparison). Rates of coronary angiography and percutaneous coronary intervention increased in all groups, but coronary artery bypass graft utilization increased only in AI/AN adults (from 7% to 10%, p <0.001). In conclusion, from 2000 to 2018, AI/AN adults had a high rate of AMI hospitalizations (second only to NH White adults) that increased significantly over time. AI/AN adults were 5 years younger than their NH White counterparts at index AMI hospitalization. Care during these hospitalizations was similar among all racial groups, and in-hospital mortality decreased for all groups, albeit to a lesser degree among AI/AN adults. This study highlights the need for improved access to outpatient primary AMI prevention in the AI/AN population.

Epidemiology and Outcomes of Aortic Stenosis in Acute Decompensated Heart Failure: The ARIC Study.

BACKGROUND: Few studies characterize the epidemiology and outcomes of aortic stenosis (AS) in acute decompensated heart failure (ADHF). This study investigates the significance of AS in contemporary patients who have experienced an ADHF hospitalization. METHODS: The ARIC study (Atherosclerosis Risk in Communities) surveilled ADHF hospitalizations for residents ≥55 years of age in 4 US communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF). Demographic differences in AS burden and the association of varying AS severities with mortality were estimated using multivariable logistic regression. RESULTS: From 2005 through 2014, there were 3597 (weighted n=16 692) ADHF hospitalizations of which 48.6% had an LVEF <50% and 51.4% an LVEF ≥50%. AS prevalence was 12.1% and 18.7% in those with an LVEF <50% and ≥50%, respectively. AS was less likely in Black than White patients regardless of LVEF: LVEF <50% (odds ratio [OR], 0.34 [95% CI, 0.28-0.42]); LVEF ≥50% (OR, 0.51 [95% CI, 0.44-0.59]). Higher AS severity was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.16 [95% CI, 1.04-1.28]); LVEF ≥50% (OR, 1.40 [95% CI, 1.28-1.54]). Sensitivity analyses excluding severe AS patients detected that mild/moderate AS was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.23 [95% CI, 1.02-1.47]); LVEF ≥50% (OR, 1.31 [95% CI, 1.14-1.51]). CONCLUSIONS: Among patients who have experienced an ADHF hospitalization, AS is prevalent and portends poor mortality outcomes. Notably, mild/moderate AS is independently associated with 1-year mortality in this high-risk population.

Patient-Specific Immersed Finite Element-Difference Model of Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) first received FDA approval for high-risk surgical patients in 2011 and has been approved for low-risk surgical patients since 2019. It is now the most common type of aortic valve replacement, and its use continues to accelerate. Computer modeling and simulation (CM&S) is a tool to aid in TAVR device design, regulatory approval, and indication in patient-specific care. This study introduces a computational fluid-structure interaction (FSI) model of TAVR with Medtronic's CoreValve Evolut R device using the immersed finite element-difference (IFED) method. We perform dynamic simulations of crimping and deployment of the Evolut R, as well as device behavior across the cardiac cycle in a patient-specific aortic root anatomy reconstructed from computed tomography (CT) image data. These IFED simulations, which incorporate biomechanics models fit to experimental tensile test data, automatically capture the contact within the device and between the self-expanding stent and native anatomy. Further, we apply realistic driving and loading conditions based on clinical measurements of human ventricular and aortic pressures and flow rates to demonstrate that our Evolut R model supports a physiological diastolic pressure load and provides informative clinical performance predictions.

Rule-based definition of muscle bundles in patient-specific models of the left atrium.

Atrial fibrillation (AF) is the most common arrhythmia encountered clinically, and as the population ages, its prevalence is increasing. Although the CHA2DS2- VASc score is the most used risk-stratification system for stroke risk in AF, it lacks personalization. Patient-specific computer models of the atria can facilitate personalized risk assessment and treatment planning. However, a challenge faced in creating such models is the complexity of the atrial muscle arrangement and its influence on the atrial fiber architecture. This work proposes a semi-automated rule-based algorithm to generate the local fiber orientation in the left atrium (LA). We use the solutions of several harmonic equations to decompose the LA anatomy into subregions. Solution gradients define a two-layer fiber field in each subregion. The robustness of our approach is demonstrated by recreating the fiber orientation on nine models of the LA obtained from AF patients who underwent WATCHMAN device implantation. This cohort of patients encompasses a variety of morphology variants of the left atrium, both in terms of the left atrial appendages (LAAs) and the number of pulmonary veins (PVs). We test the fiber construction algorithm by performing electrophysiology (EP) simulations. Furthermore, this study is the first to compare its results with other rule-based algorithms for the LA fiber architecture definition available in the literature. This analysis suggests that a multi-layer fiber architecture is important to capture complex electrical activation patterns. A notable advantage of our approach is the ability to reconstruct the main LA fiber bundles in a variety of morphologies while solving for a small number of harmonic fields, leading to a comparatively straightforward and reproducible approach.

Trends in Percutaneous Balloon Mitral Valvuloplasty Complications for Mitral Stenosis in the United States (the National Inpatient Sample [2008 to 2018]).

The epidemiology of mitral stenosis (MS) continues to evolve in the United States. Although the incidence of rheumatic MS has decreased in high-income countries, there is a paucity of data surrounding trends in percutaneous balloon mitral valvuloplasty (PBMV), the current first-line management strategy. This study aimed to identify contemporary trends in PBMV in the United States. Hospitalizations for adults (≥18 years) with MS who underwent PBMV were identified from the National Inpatient Sample from 2008 to 2018. Baseline co-morbidities and outcomes over the study period were determined using Poisson regression. There were 3,980 weighted PBMV cases, 70% of which were women. PBMV hospitalizations decreased from 603 in 2008 to 210 in 2018 (p <0.001). From 2008 to 2018, the age at hospitalization was unchanged in both female and male patients. In contrast, the Charlson Co-morbidity Index increased in both. Baseline heart failure (39% to 64%), hypertension (38% to 43%), and diabetes mellitus (17% to 26%) all substantially increased over the study period. In-hospital mortality occurred in 2% of female and 5% of male patients and was unchanged from 2008 to 2018. Vascular complications (12%) and acute kidney injury (10%) were the most frequent postprocedural complications during the 11-year study period. A composite of mortality or any postprocedural complication did not vary by gender (odds ratio 1.23, 95% confidence interval 0.88 to 1.72). In conclusion, the use of PBMV significantly decreased from 2008 to 2018, and patients with MS who underwent PBMV over this period had an increased burden of co-morbidities, elevated postprocedural complication rate, and no change in in-hospital mortality.

Five-year trends in cause-specific readmissions and cost burden of mitral transcatheter edge-to-edge repair.

OBJECTIVES: The study aimed to evaluate cost trends associated with mitral valve transcatheter edge-to-edge repair (TEER). BACKGROUND: TEER is a treatment option for patients at prohibitive surgical risk with moderate to severe mitral valve regurgitation and NYHA class III or IV symptoms. The 30-day costs and causes of readmission following TEER have not been well studied. METHODS: Patients undergoing mitral TEER in the United States from 2014 to 2018 were identified in the Nationwide Readmission Database. Patient characteristics, cause-specific readmission, and costs of the index hospitalization and readmissions were analyzed. Costs were trended over years using general linear regression. RESULTS: A total of 10,196 patients underwent mitral TEER during the study period. Thirty-day readmissions were stable over time at around 16%. The mean length of stay following TEER decreased from 7 days in 2014 to 5 days in 2018. There was a significant decline in the cost of the index hospitalization of $1311 per year, and a significant decline in the total 30-day cost of $1588 per year (p < 0.001). This was strictly due to a reduction in the cost of the index hospitalization without a change in readmission costs over time (p = 0.23). Infectious causes of readmissions significantly decreased while total cardiovascular readmissions, including heart failure, remained constant. CONCLUSION: The decreasing 30-day cost burden of TEER is primarily driven by the shorter index length of stay, as experience in TEER has grown and, length of stay has declined. However, cardiovascular readmissions, and consequently readmission costs, have remained steady.

The Relationship Between Atrial Fibrillation, Mitral Regurgitation, and Heart Failure Subtype: The ARIC Study.

BACKGROUND: Atrial fibrillation (AF) and mitral regurgitation (MR) are closely interrelated in the setting of heart failure (HF). Here we investigate the prevalence and prognostic significance of AF in patients with acute decompensated HF (ADHF) stratified by MR severity. METHODS AND RESULTS: The Atherosclerosis Risk in Communities Study investigated ADHF hospitalizations in residents greater than or equal to 55 years of age in 4 US communities. ADHF cases were stratified by MR severity (none/mild or moderate/severe) and HF subtype (HF with reduced [HFrEF] or preserved [HFpEF] ejection fraction). The odds of AF in patients with increasing MR severity was estimated using multivariable logistic regression, adjusting for age, race, sex, diabetes, hypertension, coronary artery disease, hemodialysis, stroke, and anemia. Cox regression models were used to assess the association of AF with 1-year mortality in patients with HFpEF and HFrEF, stratified by MR severity and adjusted as described, also adjusting for the year of hospitalization. From 2005 to 2014, there were 3,878 ADHF hospitalizations (17,931 weighted). AF was more likely in those with higher MR severity regardless of HF subtype; more so in HFpEF (odds ratio [OR] 1.38, 95% confidence interval [CI], 1.31-1.45) than in HFrEF (OR, 1.19, 95% CI, 1.13-1.25) (interaction P [by HF subtype] < .01). When stratified by HF type, association between AF and 1-year mortality was noted in patients with HFpEF (OR, 1.28, 95% CI 1.04-1.56) but not HFrEF (OR 0.96, 95% CI 0.79-1.16) (interaction by EF subtype, P = .02). CONCLUSIONS: In patients with ADHF, AF prevalence increased with MR severity and this effect was more pronounced in HFpEF compared with HFrEF. AF was associated with an increased 1-year mortality only in patients with HFpEF and concomitant moderate/severe MR. REGISTRATION: NCT00005131, https://clinicaltrials.gov/ct2/show/NCT00005131.

Propofol Versus Remifentanil Sedation for Transcatheter Aortic Valve Replacement: A Single Academic Center Experience.

OBJECTIVE: Comparison of remifentanil versus propofol for sedation during transcatheter aortic valve replacement (TAVR) procedures to analyze the risk of sedation-related hypoxemia and hypotension. Secondary outcomes included the rate of conversion to general anesthesia, procedure length, rate of intensive care unit (ICU) admission, ICU and hospital lengths of stay, and 30-day mortality. DESIGN: Retrospective cohort study. SETTING: A single tertiary teaching hospital. PARTICIPANTS: Two hundred fifty-nine patients who had propofol or remifentanil sedation for TAVR between March 2017 and March 2020. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: There were 130 patients (50.2%) in the propofol cohort and 129 patients (49.8%) in the remifentanil cohort. The primary outcomes were oxygen saturation nadir values and vasopressor infusion use. Remifentanil was associated with a lower oxygen saturation nadir, as compared to propofol (91.3% v . 95.4%, p < 0.001). Risk factors associated with hypoxemia (defined as <92%) were body mass index (p = 0.0004), obstructive sleep apnea (p = 0.004), and remifentanil maintenance (p < 0.001). Vasopressor infusion use was significantly higher with propofol (64.9% v . 8.5%, p < 0.001). Propofol maintenance and angiotensin-converting enzyme inhibitor/angiotensin II receptor-blocker use were the only variables identified as risk factors for vasopressor use (p < 0.001 and p = 0.009). CONCLUSIONS: For patients undergoing TAVR with conscious sedation, remifentanil was associated with more hypoxemia while propofol was associated with a higher rate of vasopressor use.

Evaluation and Management of Heart Block After Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) has developed substantially since its inception. Improvements in valve design, valve deployment technologies, preprocedural imaging and increased operator experience have led to a gradual decline in length of hospitalisation after TAVR. Despite these advances, the need for permanent pacemaker implantation for post-TAVR high-degree atrioventricular block (HAVB) has persisted and has well-established risk factors which can be used to identify patients who are at high risk and advise them accordingly. While most HAVB occurs within 48 hours of the procedure, there is a growing number of patients developing HAVB after initial hospitalisation for TAVR due to the trend for early discharge from hospital. Several observation and management strategies have been proposed. This article reviews major known risk factors for HAVB after TAVR, discusses trends in the timing of HAVB after TAVR and reviews some management strategies for observing transient HAVB after TAVR.

Effect of government-issued state of emergency and reopening orders on cardiovascular hospitalizations during the COVID-19 pandemic.

OBJECTIVE: Little is known about the effect of government-issued State of Emergency (SOE) and Reopening orders on health care behaviors. We aimed to determine the effect of SOE and Phase 1 of Reopening orders on hospitalizations for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF). METHODS: Hospitalizations for AMI and ADHF in the UNC Health system, which includes 10 hospitals in both urban and rural counties, were identified. An interrupted time series design was used to compare weekly hospitalization rates for eight weeks before the March 10th SOE declaration, eight weeks between the SOE order and Phase 1 of Reopening order, and the subsequent eight weeks. RESULTS: Overall, 3,792 hospitalizations for AMI and 7,223 for ADHF were identified. Rates before March 10th were stable. AMI/ADHF hospitalizations declined about 6% per week in both urban and rural hospitals from March 11th to May 5th. Larger declines in hospitalizations were seen in adults ≥65 years old (-8% per week), women (-7% per week), and White individuals (-6% per week). After the Reopening order, AMI/ADHF hospitalizations increased by 8% per week in urban centers and 9% per week in rural centers, including a significant increase in each demographic group. The decline and rebound in acute CV hospitalizations were most pronounced in the two weeks following the government orders. CONCLUSIONS: AMI and ADHF hospitalization rates closely correlated to SOE and Reopening orders. These data highlight the impact of public health measures on individuals seeking care for essential services; future policies may benefit from clarity regarding when individuals should present for care.

Predicting need for pacemaker implantation early and late after transcatheter aortic valve implantation.

OBJECTIVES: To identify associations with either early or late permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR) in order to develop an easily interpretable management algorithm. BACKGROUND: Injury to the conduction system after TAVR occasionally requires PPM. There is limited data on how to identify which patients will require PPM, particularly after discharge from index hospitalization after TAVR. METHODS: All patients having undergone TAVR at the University of North Carolina through August 2019 were identified and records were manually reviewed. Multivariable analyses were performed to identify associations with post-TAVR PPM due to high-degree atrioventricular block (HAVB). Comparisons were made between patients with no PPM (n = 304) and PPM required, stratified into early (during index hospitalization, n = 32) and late (during subsequent hospitalization, n = 11) PPM cohorts. RESULTS: Of the 347 patents included for analysis, 43 (12.4%) underwent post-TAVR PPM. In multivariable regression models, early PPM was associated with baseline bifascicular block (OR: 42.16; p < .001), requiring any pacing on first post-TAVR electrocardiogram (ECG) (OR: 31.55; p < .001), and valve oversizing >15% (OR: 3.61; p < .05). Late PPM was associated with baseline right bundle branch block (RBBB) (OR 12.62; p < .001) and history of atrial fibrillation/flutter (OR 4.83; p < .05). CONCLUSIONS: Bifascicular block, any pacing on first post-TAVR ECG, and >15% valve oversizing are associated with early PPM, while RBBB and history of atrial fibrillation/flutter are associated with late PPM. We suggest a management strategy for post-TAVR surveillance and management of HAVB.