Transcatheter Repair for Patients with Tricuspid Regurgitation.

BACKGROUND: Severe tricuspid regurgitation is a debilitating condition that is associated with substantial morbidity and often with poor quality of life. Decreasing tricuspid regurgitation may reduce symptoms and improve clinical outcomes in patients with this disease. METHODS: We conducted a prospective randomized trial of percutaneous tricuspid transcatheter edge-to-edge repair (TEER) for severe tricuspid regurgitation. Patients with symptomatic severe tricuspid regurgitation were enrolled at 65 centers in the United States, Canada, and Europe and were randomly assigned in a 1:1 ratio to receive either TEER or medical therapy (control). The primary end point was a hierarchical composite that included death from any cause or tricuspid-valve surgery; hospitalization for heart failure; and an improvement in quality of life as measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ), with an improvement defined as an increase of at least 15 points in the KCCQ score (range, 0 to 100, with higher scores indicating better quality of life) at the 1-year follow-up. The severity of tricuspid regurgitation and safety were also assessed. RESULTS: A total of 350 patients were enrolled; 175 were assigned to each group. The mean age of the patients was 78 years, and 54.9% were women. The results for the primary end point favored the TEER group (win ratio, 1.48; 95% confidence interval, 1.06 to 2.13; P = 0.02). The incidence of death or tricuspid-valve surgery and the rate of hospitalization for heart failure did not appear to differ between the groups. The KCCQ quality-of-life score changed by a mean (±SD) of 12.3±1.8 points in the TEER group, as compared with 0.6±1.8 points in the control group (P<0.001). At 30 days, 87.0% of the patients in the TEER group and 4.8% of those in the control group had tricuspid regurgitation of no greater than moderate severity (P<0.001). TEER was found to be safe; 98.3% of the patients who underwent the procedure were free from major adverse events at 30 days. CONCLUSIONS: Tricuspid TEER was safe for patients with severe tricuspid regurgitation, reduced the severity of tricuspid regurgitation, and was associated with an improvement in quality of life. (Funded by Abbott; TRILUMINATE Pivotal ClinicalTrials.gov number, NCT03904147.).

In Vitro Examination of the VentriFlo True Pulse Pump for Failing Fontan Support.

The current methodology of Fontan palliation results in a one "pump" circulatory system with passive flow to the lungs. Inherent hemodynamic differences exist between a biventricular circulatory system and this modified physiology, leading to a host of long-term complications. Mechanical circulatory support (MCS) is a potential option to combat these pathophysiological conditions. In this study, we examine the VentriFlo True Pulse Pump as a MCS option to support a failing Fontan patient. An in vitro circulatory loop was used to model a failing Fontan patient, reproducing pathophysiological pressures and flow rates. The VentriFlo True Pulse Pump was positioned as a right sided support, testing multiple cannulation and baffle restriction strategies, as well as various pumping parameters including flow rate, frequency, stroke volume and the ejection to filling time ratio. A 10 mm Hg decrease in IVC pressure and 0.75 L/min increase in cardiac output were achieved using a complete baffle restriction strategy. Additional cannulation and banding strategies were not as successful. Pump flow rate and frequency significantly impacted hemodynamics, while the ejection to filling time ratio did not. Though not ideal, complete baffle restriction was necessary to achieve successful support. The ability to tune individual pumping parameters for a given MCS device will have a substantial impact on the pressures and flow augmentation seen in a Fontan circulation. Both future pump design and off-label VADs for Fontan use should consider the pump configuration and parameter combinations presented here, which offered successful support.

Benchtop Flow Stasis Quantification: In Vitro Methods and In Vivo Possibilities.

PURPOSE: Neo-sinus flow stasis has ben correlated with transcatheter heart valve (THV) thrombosis severity and occurrence. Standard benchtop flow field quantification techniques require optical access or modified prosthesis models that may not reflect the true nature of the original valve. En face and fluoroscopic videodensitometry enable visualization of washout in regions otherwise unviewable. METHODS: This study compares two in vitro methods of assessing flow stasis in scenarios with insufficient optical access for traditional techniques such as particle image velocimetry (PIV). A series of seven paired experiments were conducted using a previously described laser-enhanced video densitometry (LEVD) and fluoroscopic video densitometry (FVD). Both sets of experiments were analyzed to calculate washout time as a measure of flow stasis. A novel flow stasis measure termed contrast attenuation ratio (CAR) is proposed as a viable single measure of flow stasis obtainable from only a small number of cardiac cycles of in vitro or in vivo fluoroscopic data. Retrospective fluoroscopic datasets (n = 72) were analyzed to assess the feasibility of obtaining this metric from routine clinical practice and its ability to stratify results. RESULTS: Neo-sinus flow stasis calculated from in vitro fluoroscopy was well correlated with LEVD (r2 = 0.77, p = 0.009). The newly proposed CAR metric showed good agreement with the commonly used "washout time" measure of flow stasis (r2 = 0.91, p < 0.001) while allowing for assessment with incomplete or truncated data. As a proof of concept, CAR was measured in 72 consecutive retrospective fluoroscopic datasets. CAR averaged 10.6 ± 4.6% with a range of 1.5-20.3% in these patients. CONCLUSIONS: This study demonstrates two in vitro methods that can be used to assess relative flow stasis in otherwise optically inaccessible regions surrounding cardiac or vascular implants. In addition, the fluoroscopic benchtop technique was used to validate a metric that allows for extension to routine clinical fluoroscopy. This contrast attenuation ratio (CAR) metric was found to be both accurate and clinically obtainable, and potentially offers a new method for valve thrombosis risk stratification.

Long-term durability of a new surgical aortic valve: A 1 billion cycle in vitro study.

Background: This study assessed the long-term hemodynamic functional performance of the new Inspiris Resilia aortic valve after accelerated wear testing (AWT). Methods: Three 21-mm and 23-mm Inspiris valves were used for the AWT procedure. After 1 billion cycles (equivalent to 25 years), the valves' hemodynamic performance was compared with that of the corresponding zero-cycled condition. Next, 1 AWT cycled valve of each valve size was selected at random for particle image velocimetry (PIV) and leaflet kinematic tests, and the data were compared with data for an uncycled Inspiris Resilia aortic valve of the same size. PIV was used to quantitatively evaluate flow fields downstream of the valve. Valves were tested according to International Standards Organization 5840-2:2015 protocols. Results: The 21-mm and 23-mm valves met the International Organization for Standardization (ISO) durability performance requirements to 1 billion cycles. The mean effective orifice areas for the 21-mm and 23-mm zero-cycled and 1 billion-cycled valves were 1.89 ± 0.02 cm2 and 1.94 ± 0.01 cm2, respectively (P < .05) and 2.3 ± 0.13 cm2 and 2.40 ± 0.11 cm2, respectively (P < .05). Flow characterization of the control valves and the study valves demonstrated similar flow characteristics. The velocity and shear stress fields were also similar in the control and study valves. Conclusions: The Inspiris Resilia aortic valve demonstrated very good durability and hemodynamic performance after an equivalent of 25 years of simulated in vitro accelerated wear. The study valves exceeded 1 billion cycles of simulated wear, 5 times longer than the standard requirement for a tissue valve as stipulated in ISO 5840-2:2015.

The role of flow stasis in transcatheter aortic valve leaflet thrombosis.

OBJECTIVE: With the recent expanded indication for transcatheter aortic valve replacement to low-risk surgical patients, thrombus formation in the neosinus is of particular interest due to concerns of reduced leaflet motion and long-term transcatheter heart valve durability. Although flow stasis likely plays a role, a direct connection between neosinus flow stasis and thrombus severity is yet to be established. METHODS: Patients (n = 23) were selected to minimize potential confounding factors related to thrombus formation. Patient-specific 3-dimensional reconstructed in vitro models were created to replicate in vivo anatomy and valve deployment using the patient-specific cardiac output and idealized coronary flows. Dye was injected into each neosinus to quantify washout time as a measure of flow stasis. RESULTS: Flow stasis (washout time) showed a significant, positive correlation with thrombus volume in the neosinus (rho = 0.621, P < .0001). Neither thrombus volume nor washout time was significantly different in the left, right, and noncoronary neosinuses (P ≥ .54). CONCLUSIONS: This is the first patient-specific study correlating flow stasis with thrombus volume in the neosinus post-transcatheter aortic valve replacement across multiple valve types and sizes. Neosinus-specific factors create hemodynamic and thrombotic variability within individual patients. Measurement of neosinus flow stasis may guide strategies to improve outcomes in transcatheter aortic valve replacement.

Fontan Geometry and Hemodynamics Are Associated With Quality of Life in Adolescents and Young Adults.

BACKGROUND: Despite favorable short-term outcomes, Fontan palliation is associated with comorbidities and diminished quality of life (QOL) in the years after completion. We hypothesized that poor Fontan hemodynamics and ventricular function are associated with worse QOL. METHODS: This was a single-center study of Fontan survivors aged more than 12 years. Subjects completed a cardiac magnetic resonance scan and QOL questionnaire. Cardiac magnetic resonance-derived variables included Fontan geometry, and hemodynamics. Computational fluid dynamics simulations quantified power loss, pressure drop, and total cavopulmonary connection resistance across the Fontan. Quality of life was assessed by completion of the Pediatric Quality of Life Inventory. Longitudinal and cross-sectional comparisons were made between cardiac magnetic resonance and computational fluid dynamics parameters with patient-reported QOL. RESULTS: We studied 77 Fontan patients, median age 19.7 years (interquartile range, 17.1 to 23.6), median time from Fontan completion 16 years (interquartile range, 13 to 20). Longitudinal data were available for 48 patients; median time between cardiac magnetic resonance and QOL was 8.1 years (interquartile range, 7 to 9.4). Median patient-reported Pediatric Quality of Life Inventory total score was 80 (interquartile range, 67.4 to 88). Greater power loss and smaller left pulmonary artery diameter at baseline were associated with worse QOL at follow-up. Greater pressure drop was associated with worse QOL at the same time point. CONCLUSIONS: For Fontan survivors, measures of computational fluid dynamics hemodynamics and geometry are associated with worse QOL. Interventional strategies targeted at optimizing the Fontan may improve QOL.

Transcatheter Edge-to-Edge Repair for Treatment of Tricuspid Regurgitation.

BACKGROUND: Tricuspid regurgitation (TR) is a frequent disease with a progressive increase in mortality as disease severity increases. Transcatheter therapies for treatment of TR may offer a safe and effective alternative to surgery in this high-risk population. OBJECTIVES: The purpose of this report was to study the 1-year outcomes with the TriClip transcatheter tricuspid valve repair system, including repair durability, clinical benefit and safety. METHODS: The TRILUMINATE trial (n = 85) is an international, prospective, single arm, multicenter study investigating safety and performance of the TriClip Tricuspid Valve Repair System in patients with moderate or greater TR. Echocardiographic assessment was performed by a core laboratory. RESULTS: At 1 year, TR was reduced to moderate or less in 71% of subjects compared with 8% at baseline (p < 0.0001). Patients experienced significant clinical improvements in New York Heart Association (NYHA) functional class I/II (31% to 83%, p < 0.0001), 6-minute walk test (272.3 ± 15.6 to 303.2 ± 15.6 meters, p = 0.0023) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score (improvement of 20 ± 2.61 points, p < 0.0001). Significant reverse right ventricular remodeling was observed in terms of size and function. The overall major adverse event rate and all-cause mortality were both 7.1% at 1 year. CONCLUSION: Transcatheter tricuspid valve repair using the TriClip device was found to be safe and effective in patients with moderate or greater TR. The repair itself was durable at reducing TR at 1 year and was associated with a sustained and marked clinical benefit with low mortality after 1 year in a fragile population that was at high surgical risk. (TRILUMINATE Study With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater TR; NCT03227757).

Target Flow-Pressure Operating Range for Designing a Failing Fontan Cavopulmonary Support Device.

Fontan operation as the current standard of care for the palliation of single ventricle defects results in significant late complications. Using a mechanical circulatory device for the right circulation to serve the function of the missing subpulmonary ventricle could potentially stabilize the failing Fontan circulation. This study aims to elucidate the hydraulic operating regions that should be targeted for designing cavopulmonary blood pumps. By integrating numerical analysis and available clinical information, the interaction of the cavopulmonary support via the IVC and full assist configurations with a wide range of simulated adult failing scenarios was investigated; with IVC and full assist corresponding to the inferior venous return or the entire venous return, respectively, being routed through the device. We identified the desired hydraulic operating regions for a cavopulmonary assist device by clustering all head pressures and corresponding pump flows that result in hemodynamic improvement for each simulated failing Fontan physiology. Results show that IVC support can produce beneficial hemodynamics in only a small fraction of failing Fontan scenarios. Cavopulmonary assist device could increase cardiac index by 35% and decrease the inferior vena cava pressure by 45% depending on the patient's pre-support hemodynamic state and surgical configuration of the cavopulmonary assist device (IVC or full support). The desired flow-pressure operating regions we identified can serve as the performance criteria for designing cavopulmonary assist devices as well as evaluating off-label use of commercially available left-side blood pumps for failing Fontan cavopulmonary support.

Non-Newtonian Effects on Patient-Specific Modeling of Fontan Hemodynamics.

The Fontan procedure is a common palliative surgery for congenital single ventricle patients. In silico and in vitro patient-specific modeling approaches are widely utilized to investigate potential improvements of Fontan hemodynamics that are related to long-term complications. However, there is a lack of consensus regarding the use of non-Newtonian rheology, warranting a systematic investigation. This study conducted in silico patient-specific modeling for twelve Fontan patients, using a Newtonian and a non-Newtonian model for each patient. Differences were quantified by examining clinically relevant metrics: indexed power loss (iPL), indexed viscous dissipation rate (iVDR), hepatic flow distribution (HFD), and regions of low wall shear stress (AWSS). Four sets of "non-Newtonian importance factors" were calculated to explore their effectiveness in identifying the non-Newtonian effect. No statistical differences were observed in iPL, iVDR, and HFD between the two models at the population-level, but large inter-patient variations exist. Significant differences were detected regarding AWSS, and its correlations with non-Newtonian importance factors were discussed. Additionally, simulations using the non-Newtonian model were computationally faster than those using the Newtonian model. These findings distinguish good importance factors for identifying non-Newtonian rheology and encourage the use of a non-Newtonian model to assess Fontan hemodynamics.

Cross-Sectional Magnetic Resonance and Modeling Comparison From Just After Fontan to the Teen Years.

BACKGROUND: Little is known of baseline anatomic, hemodynamic, and fluid dynamic cardiac magnetic resonance data in single-ventricle patients immediately after Fontan. A comparison from that time point to the teen years can demonstrate clinical course, potentially predict future events, and may shed some light regarding how to optimize outcome. This cross-sectional study is meant to characterize these variables from just after Fontan to the teenage years. METHODS: The anatomy, flows, and computational fluid dynamic modeling of 22 patients 3 to 9 months after Fontan (age 3 ± 1.1 years) and 25 teens (age 16 ± 1.8 years) were compared. Significance was defined as P less than .05. RESULTS: The percentage of Fontan pathway stenosis was greater with cardiac index and fenestration flow while caval return was lower in teens than in younger patients (for Fontan pathway stenosis, 43% vs 21%, P = .009); however, hepatic flow distribution was more evenly distributed in older patients. Pulmonary artery size kept up with somatic growth. In the teen group, indexed power loss (R = .39), percentage of Fontan pathway stenosis (R = .62), and particle resident time (R = .42) deteriorated as time from Fontan increased (P < .04 for all). CONCLUSIONS: There are mostly aspects of deterioration with a few bright spots of stability in anatomy, blood flow, and fluid dynamic variables in Fontan patients from the postoperative period to the teenage years. Most notably, Fontan pathway stenosis increases with decreasing flows while pulmonary artery size and hepatic flow distribution remain stable or improved. These data may be aid in designing improved Fontan reconstruction to optimize clinical outcome and to understand future complications.