ABSTRACT
BACKGROUND AND OBJECTIVE: The evidence on the role of hemodynamics in aorta pathophysiology has yet to be robustly translated into clinical applications, to improve risk stratification of aortic diseases. Motivated by the need to enrich the current understanding of the pathophysiology of the ascending aorta (AAo), this study evaluates in vivo how large-scale aortic flow coherence is affected by AAo dilation and aortic valve phenotype. METHODS: A complex networks-based approach is applied to 4D flow MRI data to quantify subject-specific AAo flow coherence in terms of correlation between axial velocity waveforms and the aortic flow rate waveform along the cardiac cycle. The anatomical length of persistence of such correlation is quantified using the recently proposed network metric average weighted curvilinear distance (AWCD). The analysis considers 107 subjects selected to allow an ample stratification in terms of aortic valve morphology, absence/presence of AAo dilation and of aortic valve stenosis. RESULTS: The analysis highlights that the presence of AAo dilation as well as of bicuspid aortic valve phenotype breaks the physiological AAo flow coherence, quantified in terms of AWCD. Of notice, it emerges that cycle-average blood flow rate and relative AAo dilation are main determinants of AWCD, playing opposite roles in promoting and hampering the persistence of large-scale flow coherence in AAo, respectively. CONCLUSIONS: The findings of this study can contribute to broaden the current mechanistic link between large-scale blood flow coherence and aortic pathophysiology, with the prospect of enriching the existing tools for the in vivo non-invasive hemodynamic risk assessment for aortic diseases onset and progression.
Subject(s)
Aorta , Aortic Valve , Magnetic Resonance Imaging , Phenotype , Humans , Aorta/diagnostic imaging , Aorta/physiopathology , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Magnetic Resonance Imaging/methods , Male , Female , Middle Aged , Adult , Hemodynamics , Blood Flow Velocity , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Aged , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/diagnostic imagingSubject(s)
Aortic Valve Stenosis , Aortic Valve , Bicuspid Aortic Valve Disease , Clinical Decision-Making , Heart Valve Diseases , Heart Valve Prosthesis , Patient Selection , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/instrumentation , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve/abnormalities , Treatment Outcome , Bicuspid Aortic Valve Disease/surgery , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/diagnostic imaging , Heart Valve Diseases/surgery , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/physiopathology , Risk Factors , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Risk Assessment , Prosthesis DesignABSTRACT
BACKGROUND: Outcomes from transcatheter aortic valve replacement (TAVR) in low-surgical risk patients with bicuspid aortic stenosis beyond 2 years are limited. OBJECTIVES: This study aimed to evaluate 3-year clinical and echocardiographic outcomes from the Evolut Low Risk Bicuspid Study. METHODS: The Evolut Low Risk Bicuspid Study is a prospective, multicenter, single-arm study conducted in 25 U.S. CENTERS: Patients with severe aortic stenosis at low surgical risk with bicuspid aortic valve anatomy (all subtypes) underwent TAVR with a self-expanding, supra-annular Evolut R or PRO (Medtronic) bioprosthesis. An independent clinical events committee adjudicated all deaths and endpoint-related adverse events, and a central echocardiographic core laboratory assessed hemodynamic endpoints. RESULTS: An attempted implant was performed in 150 patients from December 2018 to October 2019. The mean age was 70.3 ± 5.5 years, 48% (72/150) of the patients were women, and the mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 1.3% (Q1-Q3: 0.9%-1.7%). Sievers type 1 was the dominant bicuspid morphology (90.7%, 136/150). The Kaplan-Meier rates of all-cause mortality or disabling stroke were 1.3% (95% CI: 0.3%-5.3%) at 1 year, 3.4% (95% CI: 1.4%-8.1%) at 2 years, and 4.1% (95% CI: 1.6%-10.7%) at 3 years. The incidence of new permanent pacemaker implantation was 19.4% (95% CI: 12.4%-29.6%) at 3 years. There were no instances of moderate or severe paravalvular aortic regurgitation at 2 and 3 years after TAVR. CONCLUSIONS: The 3-year results from the Evolut Low Risk Bicuspid Study demonstrate low rates of all-cause mortality or disabling stroke and favorable hemodynamic performance.
Subject(s)
Aortic Valve Stenosis , Aortic Valve , Bicuspid Aortic Valve Disease , Bioprosthesis , Heart Valve Prosthesis , Hemodynamics , Prosthesis Design , Transcatheter Aortic Valve Replacement , Humans , Female , Male , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/mortality , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/mortality , Transcatheter Aortic Valve Replacement/instrumentation , Aged , Risk Factors , Prospective Studies , Time Factors , Treatment Outcome , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve/abnormalities , Risk Assessment , Bicuspid Aortic Valve Disease/surgery , Bicuspid Aortic Valve Disease/physiopathology , United States/epidemiology , Severity of Illness Index , Postoperative Complications/mortality , Recovery of Function , Aged, 80 and over , Middle Aged , Heart Valve Diseases/physiopathology , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/surgery , Heart Valve Diseases/mortalitySubject(s)
Aortic Valve Stenosis , Aortic Valve , Bicuspid Aortic Valve Disease , Transcatheter Aortic Valve Replacement , Humans , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/instrumentation , Treatment Outcome , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve/abnormalities , Bicuspid Aortic Valve Disease/surgery , Bicuspid Aortic Valve Disease/diagnostic imaging , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/complications , Risk Factors , Heart Valve Prosthesis , Heart Valve Diseases/surgery , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/physiopathology , Heart Valve Diseases/complications , Clinical Decision-Making , Recovery of Function , Risk AssessmentSubject(s)
Aortic Valve , Bicuspid Aortic Valve Disease , Heart Valve Diseases , Humans , Aortic Valve/abnormalities , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Bicuspid Aortic Valve Disease/surgery , Bicuspid Aortic Valve Disease/complications , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/diagnostic imaging , Bicuspid Aortic Valve Disease/diagnosis , Heart Valve Diseases/complications , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/surgery , Heart Valve Diseases/physiopathology , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/etiology , Risk Factors , Action PotentialsSubject(s)
Aortic Valve , Bicuspid Aortic Valve Disease , Heart Valve Diseases , Pregnancy Complications, Cardiovascular , Pregnancy Outcome , Humans , Pregnancy , Female , Aortic Valve/abnormalities , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Bicuspid Aortic Valve Disease/complications , Bicuspid Aortic Valve Disease/surgery , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/diagnosis , Heart Valve Diseases/diagnosis , Heart Valve Diseases/complications , AdultSubject(s)
Aortic Valve , Bicuspid Aortic Valve Disease , Heart Valve Diseases , Humans , Aortic Valve/abnormalities , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Bicuspid Aortic Valve Disease/surgery , Bicuspid Aortic Valve Disease/complications , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/diagnostic imaging , Bicuspid Aortic Valve Disease/diagnosis , Male , Heart Valve Diseases/complications , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/physiopathology , Heart Valve Diseases/surgery , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/etiology , Female , Middle Aged , Action Potentials , Electrocardiography , Adult , Heart RateABSTRACT
INTRODUCTION: Bicuspid aortic valve (BAV) stenosis is a complex anatomical scenario for transcatheter aortic valve implantation (TAVI). Favorable short-term clinical outcomes have been reported with TAVI in this setting, but long-term data are scarce. METHODS: We retrospectively included, in a single-center registry, patients with BAV stenosis who underwent TAVI before 2020. We compared patients treated with self-expanding valves (SEV) versus balloon-expandable valves (BEV). The primary endpoint was a composite of all-cause mortality, stroke and need for aortic valve (AV) reintervention at 3 years. Secondary endpoints included each component of the primary endpoint, cardiovascular mortality, permanent pacemaker implantation (PPI) rate, mean gradient and ≥moderate paravalvular leak (PVL) rate. RESULTS: A total of 150 consecutive patients (SEV = 83, BEV = 67) were included. No significant differences were reported between SEV and BEV groups for the primary composite endpoint (SEV 35.9% vs. BEV 32%, p = 0.66), neither for clinical secondary endpoints (all-cause mortality SEV 28.1% vs. BEV 28%, p = 0.988; cardiovascular mortality SEV 14.1% vs. BEV 20%, p = 0.399; stroke SEV 12.5% vs. BEV 6%, p = 0.342; need for AV reintervention SEV 0% vs. BEV 0%; PPI SEV 28.1% vs. BEV 24%, p = 0.620). A lower mean gradient persisted up to 3 years in the SEV group (SEV 8.8 ± 3.8 mmHg vs. BEV 10.7 ± 3.2 mmHg, p = 0.063), while no significant difference was found in the rate of ≥ moderate PVL (SEV 3/30 vs. BEV 0/25, p = 0.242). CONCLUSIONS: In this single center registry, we observed favorable 3-year clinical outcomes in nonselected BAV patients treated with different generation devices, without significant differences between patients receiving SEV or BEV.
Subject(s)
Aortic Valve Stenosis , Balloon Valvuloplasty , Bicuspid Aortic Valve Disease , Heart Valve Prosthesis , Prosthesis Design , Registries , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/instrumentation , Transcatheter Aortic Valve Replacement/mortality , Male , Female , Retrospective Studies , Treatment Outcome , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/diagnostic imaging , Bicuspid Aortic Valve Disease/mortality , Bicuspid Aortic Valve Disease/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/mortality , Time Factors , Aged , Balloon Valvuloplasty/adverse effects , Balloon Valvuloplasty/mortality , Aged, 80 and over , Risk Factors , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve/physiopathology , Aortic Valve/abnormalities , Recovery of Function , Hemodynamics , Risk AssessmentABSTRACT
INTRODUCTION: Bicuspid aortic valves (BAV) are the most common congenital heart defects and the extent of ventricular arrhythmias (VA) in patients with BAV is unclear. The objective of this study is to describe VAs and late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) in patients with BAV. METHODS: A total of 19 patients with BAV (18 males, age: 58 ± 13 years) were referred for VA ablation procedures. Ten patients had BAVs at the time of ablation, nine patients had prior aortic valve replacement for a BAV. All but one patient had LGE-CMR and all patients underwent programmed ventricular stimulation at the time of the ablation. RESULTS: Frequent PVCs were the targeted VAs in 17/19 patients and VT in 2/19 patients. Monomorphic ventricular tachycardia (VT) was inducible in 6 patients. A total of 15 VTs were inducible (2.5 ± 1.0 VTs per patient with a mean cycle length of 322 ± 83 msec). LGE was present in 13 patients. Patients with inducible VT had larger borderzone and core scar compared to non-inducible patients (7.8 ± 2.1 cm3 vs. 2.5 ± 3.1 cm3 and 5.1 ± 2.6 cm3 vs. 1.9 ± 3.0 cm3, p-value < .05 for both). PVCs and VTs were mapped to the periaortic valve area in 12 patients and 4 patients, respectively. The PVC burden was reduced from 27 ± 13 to 3 ± 6 (p < .001) and the ejection fraction improved from 49 ± 13% to 55 ± 9% (p = .005). CONCLUSIONS: VAs in patients with BAV often originate from the perivalvular area and patients often have LGE and inducible VT. LGE may be due to ventricular remodeling secondary to the presence of BAV and harbors the arrhythmogenic substrate for VT.
Subject(s)
Bicuspid Aortic Valve Disease , Tachycardia, Ventricular , Humans , Male , Female , Middle Aged , Bicuspid Aortic Valve Disease/surgery , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/complications , Bicuspid Aortic Valve Disease/diagnostic imaging , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Aged , Adult , Aortic Valve/surgery , Aortic Valve/abnormalities , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Catheter Ablation , Action Potentials , Heart Valve Diseases/physiopathology , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/complications , Heart Valve Diseases/surgery , Heart Rate , Treatment Outcome , Risk Factors , Predictive Value of Tests , Retrospective Studies , Electrophysiologic Techniques, Cardiac , Contrast Media/administration & dosage , Magnetic Resonance Imaging, CineSubject(s)
Aortic Valve , Bicuspid Aortic Valve Disease , Computed Tomography Angiography , Heart Valve Diseases , Predictive Value of Tests , Transcatheter Aortic Valve Replacement , Humans , Aortic Valve/diagnostic imaging , Aortic Valve/abnormalities , Aortic Valve/surgery , Aortic Valve/physiopathology , Bicuspid Aortic Valve Disease/diagnostic imaging , Bicuspid Aortic Valve Disease/surgery , Bicuspid Aortic Valve Disease/physiopathology , Female , Male , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/physiopathology , Heart Valve Diseases/surgery , Aged , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/surgery , Aortography , Aged, 80 and over , Retrospective Studies , Aorta/diagnostic imagingSubject(s)
Aortic Valve Stenosis , Aortic Valve , Bicuspid Aortic Valve Disease , Heart Valve Diseases , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/instrumentation , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Aortic Valve/abnormalities , Aortic Valve/physiopathology , Bicuspid Aortic Valve Disease/surgery , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/diagnostic imaging , Bicuspid Aortic Valve Disease/complications , Heart Valve Diseases/surgery , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/physiopathology , Treatment Outcome , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Risk Factors , Prosthesis DesignABSTRACT
BACKGROUND: There continues to be debate regarding the superiority of transcatheter (TAVR) over surgical aortic valve replacement (SAVR) in patients with bicuspid aortic valves (BAV). We aimed to compare outcomes during readmissions in elderly patients with BAV who underwent SAVR or TAVR. METHODS: Patients 65 years or older with BAV who underwent TAVR or isolated SAVR were identified using the National Readmission Database from 2012 through 2018. We compared outcomes during readmissions within 90 days after discharge from the index surgery. Propensity score matching was performed to adjust the baseline differences. RESULTS: During the study period, 8555 and 1081 elderly patients with BAV underwent SAVR and TAVR, respectively. The number of patients who underwent TAVR went up by 179 % from 2012 to 2018. Propensity score matching yielded 573 patients in each group. A total of 111 (19.4 %) in the SAVR group and 125 (21.8 %) in the TAVR group were readmitted within 90 days after the index surgery (p = .31). The mortality during the readmissions within 90 days was equivalent between the two groups (0.9 % in the SAVR group vs. 3.2 % in the TAVR group, p = .22). However, the median hospital cost was approximately doubled in the TAVR group during the readmission (18,250 dollars vs. 9310 dollars in the SAVR group, p < .001). CONCLUSIONS: Readmission within 90 days was common in both groups. While the mortality during the readmissions after the surgery was equivalent between the two groups, hospital cost was significantly more expensive in the TAVR group.
Subject(s)
Aortic Valve , Bicuspid Aortic Valve Disease , Databases, Factual , Heart Valve Diseases , Heart Valve Prosthesis Implantation , Patient Readmission , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/mortality , Transcatheter Aortic Valve Replacement/economics , Male , Female , Aged , Treatment Outcome , Time Factors , Bicuspid Aortic Valve Disease/surgery , Bicuspid Aortic Valve Disease/diagnostic imaging , Bicuspid Aortic Valve Disease/mortality , Bicuspid Aortic Valve Disease/physiopathology , Aged, 80 and over , Aortic Valve/surgery , Aortic Valve/abnormalities , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Risk Factors , United States , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/mortality , Heart Valve Prosthesis Implantation/economics , Retrospective Studies , Age Factors , Risk Assessment , Heart Valve Diseases/surgery , Heart Valve Diseases/mortality , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/physiopathology , Postoperative Complications/etiology , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/physiopathologyABSTRACT
OBJECTIVES: To assess intermediate-term outcomes of aortic root replacement with valve-sparing reimplantation of bicuspid aortic valves (BAV), compared with tricuspid aortic valves (TAV). METHODS: From January 2002 to July 2017, 92 adults underwent aortic root replacement with BAV reimplantation and 515 with TAV reimplantation at the Cleveland Clinic. Balancing-score matching based on 28 preoperative variables yielded 71 well-matched BAV and TAV pairs (77% of possible pairs) for comparison of postoperative mortality and morbidity, longitudinal echocardiogram data, aortic valve reoperation, and survival. RESULTS: In the BAV group, 1 hospital death occurred (1.1%); mortality among all reimplantations was 0.2%. Among matched patients, procedural morbidity was low and similar between BAV and TAV groups (1 stroke in TAV group; renal failure requiring dialysis, 1 patient each; red cell transfusion, 25% each). Five-year results: Severe aortic regurgitation was present in 7.4% of the BAV group and 2.9% of the TAV group (P = .7); 39% of BAV and 65% of TAV patients had none. Higher mean gradients (10 vs 7.4 mm Hg; P = .001) and left ventricular mass index (111 vs 101 g/m2; P = .5) were present in BAV patients. Freedom from aortic valve reoperation was 94% in the BAV group and 98% in the TAV group (P = .10), and survival was 100% and 95%, respectively (P = .07). CONCLUSIONS: Both BAV and TAV reimplantations can be performed with equal safety and good midterm outcomes; however, the constellation of higher gradients, less ventricular reverse remodeling, and more aortic valve reoperations with BAV reimplantations raises concerns requiring continued long-term surveillance.
Subject(s)
Aortic Valve , Bicuspid Aortic Valve Disease , Cardiac Valve Annuloplasty , Heart Valve Prosthesis Implantation , Long Term Adverse Effects , Postoperative Complications , Replantation , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Aortic Valve/physiopathology , Aortic Valve/surgery , Aortic Valve Insufficiency/diagnosis , Aortic Valve Insufficiency/physiopathology , Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/surgery , Bicuspid Aortic Valve Disease/diagnosis , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/surgery , Cardiac Valve Annuloplasty/adverse effects , Cardiac Valve Annuloplasty/methods , Female , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/methods , Humans , Long Term Adverse Effects/diagnosis , Long Term Adverse Effects/etiology , Long Term Adverse Effects/prevention & control , Male , Middle Aged , Organ Sparing Treatments/methods , Outcome and Process Assessment, Health Care , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/mortality , Postoperative Complications/surgery , Reoperation/methods , Reoperation/statistics & numerical data , Replantation/adverse effects , Replantation/methods , Survival Analysis , United States/epidemiologyABSTRACT
OBJECTIVE: The objective was to design and evaluate a clinically relevant, novel ex vivo bicuspid aortic valve model that mimics the most common human phenotype with associated aortic regurgitation. METHODS: Three bovine aortic valves were mounted asymmetrically in a previously validated 3-dimensional-printed left heart simulator. The non-right commissure and the non-left commissure were both shifted slightly toward the left-right commissure, and the left and right coronary cusps were sewn together. The left-right commissure was then detached and reimplanted 10 mm lower than its native height. Free margin shortening was used for valve repair. Hemodynamic status, high-speed videography, and echocardiography data were collected before and after the repair. RESULTS: The bicuspid aortic valve model was successfully produced and repaired. High-speed videography confirmed prolapse of the fused cusp of the baseline bicuspid aortic valve models in diastole. Hemodynamic and pressure data confirmed accurate simulation of diseased conditions with aortic regurgitation and the subsequent repair. Regurgitant fraction postrepair was significantly reduced compared with that at baseline (14.5 ± 4.4% vs 28.6% ± 3.4%; P = .037). There was no change in peak velocity, peak gradient, or mean gradient across the valve pre- versus postrepair: 293.3 ± 18.3 cm/sec versus 325.3 ± 58.2 cm/sec (P = .29), 34.3 ± 4.2 mm Hg versus 43.3 ± 15.4 mm Hg (P = .30), and 11 ± 1 mm Hg versus 9.3 ± 2.5 mm Hg (P = .34), respectively. CONCLUSIONS: An ex vivo bicuspid aortic valve model was designed that recapitulated the most common human phenotype with aortic regurgitation. These valves were successfully repaired, validating its potential for evaluating valve hemodynamics and optimizing surgical repair for bicuspid aortic valves.
Subject(s)
Aortic Valve Insufficiency , Bicuspid Aortic Valve Disease , Cardiovascular Surgical Procedures , Models, Anatomic , Animals , Aortic Valve Insufficiency/etiology , Aortic Valve Insufficiency/pathology , Aortic Valve Insufficiency/physiopathology , Aortic Valve Insufficiency/surgery , Bicuspid Aortic Valve Disease/pathology , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/surgery , Cardiovascular Surgical Procedures/education , Cardiovascular Surgical Procedures/methods , Cattle , Echocardiography , Hemodynamics , HumansABSTRACT
OBJECTIVE: Explore the factors affecting the QO of life after transcatheter aortic valve replacement (TAVR) and analyze and evaluate their surgical efficacy and postoperative survival status. METHODS: Through correlation analysis and multiple regression analysis, we predict various clinical characteristics and postoperative quality and predict clinical changes in L postoperative quality. RESULTS: The quality of life of patients with the disease has gradually improved and improved from 6 months after surgery. The differences in the three aspects of its physiological mechanism function, physiological function function, overall health, and vitality are statistically significant (p < 0.05). CONCLUSION: Compared with traditional open-thoracic aortic valve (AV) surgery, TAVR has the significant advantages of smaller surgical incision and less trauma to the patient, which has become one of the reasons why patients are willing to accept it.
Subject(s)
Aortic Valve Stenosis/surgery , Transcatheter Aortic Valve Replacement , Adult , Aged , Aortic Valve Insufficiency/etiology , Aortic Valve Insufficiency/physiopathology , Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/physiopathology , Bicuspid Aortic Valve Disease/mortality , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/surgery , China/epidemiology , Computational Biology , Female , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis Implantation/methods , Humans , Male , Middle Aged , Quality of Life , Risk Factors , Stroke/etiology , Survival Rate , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Transcatheter Aortic Valve Replacement/mortalityABSTRACT
Bicuspid aortic valve (BAV) is the most common congenital heart disease. Calcific aortic valve disease (CAVD) accounts for the majority of aortic stenosis (AS) cases. Half of the patients diagnosed with AS have a BAV, which has an accelerated progression rate. This study aims to develop a computational modeling approach of both the calcification progression in BAV, and its biomechanical response incorporating fluid-structure interaction (FSI) simulations during the disease progression. The calcification is patient-specifically reconstructed from Micro-CT images of excised calcified BAV leaflets, and processed with a novel reverse calcification technique that predicts prior states of CAVD using a density-based criterion, resulting in a multilayered calcified structure. Four progressive multilayered calcified BAV models were generated: healthy, mild, moderate, and severe, and were modeled by FSI simulations during the full cardiac cycle. A valve apparatus model, composed of the excised calcified BAV leaflets, was tested in an in-vitro pulse duplicator, to validate the severe model. The healthy model was validated against echocardiography scans. Progressive AS was characterized by higher systolic jet flow velocities (2.08, 2.3, 3.37, and 3.85 m s-1), which induced intense vortices surrounding the jet, coupled with irregular recirculation backflow patterns that elevated viscous shear stresses on the leaflets. This study shed light on the fluid-structure mechanism that drives CAVD progression in BAV patients.
Subject(s)
Aortic Valve Stenosis/etiology , Aortic Valve Stenosis/physiopathology , Aortic Valve/pathology , Bicuspid Aortic Valve Disease/physiopathology , Calcinosis/etiology , Calcinosis/physiopathology , Heart Defects, Congenital/complications , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve Stenosis/diagnostic imaging , Biomechanical Phenomena , Calcinosis/diagnostic imaging , Computer Simulation , Disease Progression , Hemodynamics , Humans , In Vitro Techniques , Models, Cardiovascular , X-Ray MicrotomographyABSTRACT
Background: Bicuspid aortic valve (BAV) is the most common congenital cardiovascular disease in general population and is frequently associated with the development of thoracic aortic aneurysm (TAA). There is no effective strategy to intervene with TAA progression due to an incomplete understanding of the pathogenesis. Insufficiency of NOTCH1 expression is highly related to BAV-TAA, but the underlying mechanism remains to be clarified. Methods: A comparative proteomics analysis was used to explore the biological differences between non-diseased and BAV-TAA aortic tissues. A microfluidics-based aorta smooth muscle-on-a-chip model was constructed to evaluate the effect of NOTCH1 deficiency on contractile phenotype and mitochondrial dynamics of human aortic smooth muscle cells (HAoSMCs). Results: Protein analyses of human aortic tissues showed the insufficient expression of NOTCH1 and impaired mitochondrial dynamics in BAV-TAA. HAoSMCs with NOTCH1-knockdown exhibited reduced contractile phenotype and were accompanied by attenuated mitochondrial fusion. Furthermore, we identified that mitochondrial fusion activators (leflunomide and teriflunomide) or mitochondrial fission inhibitor (Mdivi-1) partially rescued the disorders of mitochondrial dynamics in HAoSMCs derived from BAV-TAA patients. Conclusions: The aorta smooth muscle-on-a-chip model simulates the human pathophysiological parameters of aorta biomechanics and provides a platform for molecular mechanism studies of aortic disease and related drug screening. This aorta smooth muscle-on-a-chip model and human tissue proteomic analysis revealed that impaired mitochondrial dynamics could be a potential therapeutic target for BAV-TAA. Funding: National Key R and D Program of China, National Natural Science Foundation of China, Shanghai Municipal Science and Technology Major Project, Shanghai Science and Technology Commission, and Shanghai Municipal Education Commission.
To function properly, the heart must remain a one-way system, pumping out oxygenated blood into the aorta the largest artery in the body so it can be distributed across the organism. The aortic valve, which sits at the entrance of the aorta, is a key component of this system. Its three flaps (or 'cusps') are pushed open when the blood exits the heart, and they shut tightly so it does not flow back in the incorrect direction. Nearly 1.4% of people around the world are born with 'bicuspid' aortic valves that only have two flaps. These valves may harden or become leaky, forcing the heart to work harder. This defect is also associated with bulges on the aorta which progressively weaken the artery, sometimes causing it to rupture. Open-heart surgery is currently the only way to treat these bulges (or 'aneurysms'), as no drug exists that could slow down disease progression. This is partly because the biological processes involved in the aneurysms worsening and bursting open is unclear. Recent studies have highlighted that many individuals with bicuspid aortic valves also have lower levels of a protein known as NOTCH1, which plays a key signalling role for cells. Problems in the mitochondria the structures that power up a cell are also observed. However, it is not known how these findings are connected or linked with the aneurysms developing. To answer this question, Abudupataer et al. analyzed the proteins present in diseased and healthy aortic muscle cells, confirming a lower production of NOTCH1 and impaired mitochondria in diseased tissues. They also created an 'aorta-on-a-chip' model where aortic muscle cells were grown in the laboratory under conditions resembling those found in the body including the rhythmic strain that the aorta is under because of the heart beating. Abudupataer et al. then reduced NOTCH1 levels in healthy samples, which made the muscle tissue less able to contract and reduced the activity of the mitochondria. Applying drugs that tweak mitochondrial activity helped tissues from patients with bicuspid aortic valves to work better. These compounds could potentially benefit individuals with deficient aortic valves, but experiments in animals and clinical trials would be needed first to confirm the results and assess safety. The aorta-on-a-chip model developed by Abudupataer et al. also provides a platform to screen for drugs and examine the molecular mechanisms at play in aortic diseases.
Subject(s)
Aortic Aneurysm , Bicuspid Aortic Valve Disease , Mitochondrial Dynamics , Myocytes, Smooth Muscle , Tissue Array Analysis/methods , Adult , Aged , Aorta/cytology , Aorta/drug effects , Aortic Aneurysm/metabolism , Aortic Aneurysm/physiopathology , Bicuspid Aortic Valve Disease/metabolism , Bicuspid Aortic Valve Disease/physiopathology , Cardiovascular Agents/pharmacology , Cell Line , Female , Humans , Lab-On-A-Chip Devices , Male , Middle Aged , Mitochondrial Dynamics/drug effects , Mitochondrial Dynamics/physiology , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolismABSTRACT
The incidence of bicuspid aortic valves (BAV) is high in the whole population, BAV-related thoracic aortic aneurysm (TAA) is accompanied by many adverse vascular events. So far, there are two key points in dealing with BAV-related TAA. First is fully understanding on its pathogenesis. Second is optimizing surgical intervention time. This review aims to illustrate the potential role of miRNAs in both aspects, that is, how miRNAs are involved in the occurrence and progression of BAV-related TAA, and the feasibilities of miRNAs as biomarkers.
Subject(s)
Aortic Aneurysm, Thoracic , Bicuspid Aortic Valve Disease , MicroRNAs , Aortic Aneurysm, Thoracic/etiology , Aortic Aneurysm, Thoracic/genetics , Aortic Aneurysm, Thoracic/physiopathology , Aortic Aneurysm, Thoracic/surgery , Aortic Valve/abnormalities , Aortic Valve/surgery , Bicuspid Aortic Valve Disease/etiology , Bicuspid Aortic Valve Disease/genetics , Bicuspid Aortic Valve Disease/physiopathology , Bicuspid Aortic Valve Disease/surgery , Biomarkers/analysis , Disease Progression , Humans , MicroRNAs/analysis , MicroRNAs/geneticsABSTRACT
OBJECTIVE: To elucidate sex differences in valve morphology, disease phenotype, progression, and outcomes among children and young adults with bicuspid aortic valve (BAV). PATIENTS AND METHODS: This is a retrospective cohort study examining all children and young adults (aged ≤22 years) with isolated BAV diagnosed, by excluding patients with concomitant congenital heart defects or genetic syndromes, from January 1, 1990, through December 1, 2016, at Mayo Clinic in Rochester, Minnesota. RESULTS: Of 1010 patients with BAV, 558 had isolated BAV. Distributions of morphology were right-left in 65.8% (n=367), right-noncoronary in 34% (n=190), and left-noncoronary cusp fusion in 0.2% (n=1) of patients; with no sex differences. Male to female ratio was 3:1. At the first echocardiographic evaluation in the study, there were no sex differences in terms of frequency of aortic valve stenosis or regurgitation. However, males had significantly higher grades of aortic valve regurgitation at 17 years of age onward (P<.0001). Males had significantly larger mid-ascending aorta (P=.01) and sinus of Valsalva dimensions (z score; P=.0001) as compared with females, with a novel finding of peak aortic dimensions around 8 years of age. Males also had more than 2-fold higher risk for sinus of Valsalva dilation (z score >2) as compared with females (odds ratio, 2.3; 95% CI, 1.2 to 4.2; P=.01). There were no significant sex differences in the primary cardiac outcomes of interventions on aortic valve and/or aorta, aortic dissection, or death. CONCLUSION: In children and young adults with BAV, males have a higher grade of aortic regurgitation in late adolescence, significantly larger aortic dimensions, different patterns of aortic growth, and more frequent sinus of Valsalva dilation as compared with females. Overall, the rate of primary cardiac events is lower in young patients, with no significant sex differences.
Subject(s)
Aorta , Aortic Valve , Bicuspid Aortic Valve Disease , Echocardiography/methods , Sex Factors , Sinus of Valsalva , Adolescent , Age Factors , Aorta/diagnostic imaging , Aorta/growth & development , Aorta/pathology , Aortic Valve/abnormalities , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve Insufficiency/diagnosis , Aortic Valve Insufficiency/etiology , Bicuspid Aortic Valve Disease/diagnosis , Bicuspid Aortic Valve Disease/physiopathology , Biological Variation, Population , Child , Disease Progression , Female , Humans , Male , Organ Size , Sinus of Valsalva/diagnostic imaging , Sinus of Valsalva/pathologyABSTRACT
BACKGROUND: The dilation of the aorta that occurs as a consequence of a congenitally bicuspid aortic valve (BAV) is associated with a risk of dissection, aneurysm or rupture. With progressive aortopathy, surgery is often recommended, but current patient selection strategies have limitations. A blood-based assay to identify those who would most benefit from prophylactic surgery would be an important medical advance. In a proof-of-concept study, we sought to identify aorta-specific differentially methylated regions (DMRs) detectable in plasma cell-free DNA (cfDNA) obtained from patients undergoing surgery for BAV-associated aortopathy. METHODS: We used bioinformatics and publicly available human methylomes to identify aorta-specific DMRs. We used data from 4D-flow cardiac magnetic resonance imaging to identify regions of elevated aortic wall shear stress (WSS) in patients with BAV-associated aortopathy undergoing surgery and correlated WSS regions with aortic tissue cell death assessed using TUNEL staining. Cell-free DNA was isolated from patient plasma, and levels of candidate DMRs were correlated with aortic diameter and aortic wall cell death. RESULTS: Aortic wall cell death was not associated with maximal aortic diameter but was significantly associated with elevated WSS. We identified 24 candidate aorta-specific DMRs and selected 4 for further study. A DMR on chromosome 11 was specific for the aorta and correlated significantly with aortic wall cell death. Plasma levels of total and aorta-specific cfDNA did not correlate with aortic diameter. CONCLUSIONS: In a cohort of patients undergoing surgery for BAV-associated aortopathy, elevated WSS created by abnormal flow hemodynamics was associated with increased aortic wall cell death which supports the use of aorta-specific cfDNA as a potential tool to identify aortopathy and stratify patient risk.