Examining the typical hemodynamic performance of nearly 3000 modern surgical aortic bioprostheses.

OBJECTIVES: The objective of this analysis was to assess the normal haemodynamic performance of contemporary surgical aortic valves at 1 year postimplant in patients undergoing surgical aortic valve replacement for significant valvular dysfunction. By pooling data from 4 multicentre studies, this study will contribute to a better understanding of the effectiveness of surgical aortic valve replacement procedures, aiding clinicians and researchers in making informed decisions regarding valve selection and patient management. METHODS: Echocardiograms were assessed by a single core laboratory. Effective orifice area, dimensionless velocity index, mean aortic gradient, peak aortic velocity and stroke volume were evaluated. RESULTS: The cohort included 2958 patients. Baseline age in the studies ranged from 70.1 ± 9.0 to 83.3 ± 6.4 years, and Society of Thoracic Surgeons risk of mortality was 1.9 ± 0.7 to 7.5 ± 3.4%. Twenty patients who had received a valve model implanted in fewer than 10 cases were excluded. Ten valve models (all tissue valves; n = 2938 patients) were analysed. At 1 year, population mean effective orifice area ranged from 1.46 ± 0.34 to 2.12 ± 0.59 cm2, and dimensionless velocity index, from 0.39 ± 0.07 to 0.56 ± 0.15. The mean gradient ranged from 8.6 ± 3.4 to 16.1 ± 6.2 mmHg with peak aortic velocity of 1.96 ± 0.39 to 2.65 ± 0.47 m/s. Stroke volume was 75.3 ± 19.6 to 89.8 ± 24.3 ml. CONCLUSIONS: This pooled cohort is the largest to date of contemporary surgical aortic valves with echocardiograms analysed by a single core lab. Overall haemodynamic performance at 1 year ranged from good to excellent. These data can serve as a benchmark for other studies and may be useful to evaluate the performance of bioprosthetic surgical valves over time. CLINICAL TRIAL REGISTRATION NUMBER: NCT02088554, NCT02701283, NCT01586910 and NCT01531374.

Impact of nondiameter aortic indices on surgical eligibility: Results from the Treatment in Thoracic Aortic Aneurysm: Surgery Versus Surveillance (TITAN: SvS) randomized controlled trial.

OBJECTIVES: Traditional criterion for intervention on an asymptomatic ascending aortic aneurysm has been a maximal aortic diameter of 5.5 cm or more. The 2022 American College of Cardiology/American Heart Association aortic guidelines adopted cross-sectional aortic area/height ratio, aortic size index, and aortic height index as alternate parameters for surgical intervention. The objective of this study was to evaluate the impact of using these newer indices on patient eligibility for surgical intervention in a prospective, multicenter cohort with moderate-sized ascending aortic aneurysms between 5.0 and 5.4 cm. METHODS: Patients enrolled from 2018 to 2023 in the randomization or registry arms of the multicenter trial, Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance, were included in the study. Clinical data were captured prospectively in an online database. Imaging data were derived from a core computed laboratory. RESULTS: Among the 329 included patients, 20% were female. Mean age was 65.0 ± 11.6 years, and mean maximal aortic diameter was 50.8 ± 3.9 mm. In the one-third of all patients (n = 109) who met any 1 of the 3 criteria (ie, aortic size index ≥3.08 cm/m2, aortic height index ≥3.21 cm/m, or cross-sectional aortic area/height ≥ 10 cm2/m), their mean maximal aortic diameter was 52.5 ± 0.52 mm. Alternate criteria were most commonly met in women compared with men: 20% versus 2% for aortic size index (P < .001), 39% versus 5% for aortic height index (P < .001), and 39% versus 21% for cross-sectional aortic area/height (P = .002), respectively. CONCLUSIONS: One-third of patients in Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance would meet criteria for surgical intervention based on novel parameters versus the classic definition of diameter 5.5 cm or more. Surgical thresholds for aortic size index, aortic height index, or cross-sectional aortic area/height ratio are more likely to be met in female patients compared with male patients.

Angiotensin II receptor blockers are associated with reduced valvular fibrosis in females with aortic stenosis.

BACKGROUND: Angiotensin receptor blockers (ARBs) may slow down the progression of aortic stenosis (AS), through their antifibrotic effect. Females present more valvular fibrosis than males, thus ARBs may have more effect in females. Our aim was to assess the impact of ARBs on the remodeling of the aortic valve in males and females. METHODS: We included patients who had an aortic valve replacement± coronary bypass grafting between 2006-2013. Patients with missing echocardiographic or histologic data were excluded. Warren-Yong and fibrosis scores of the explanted valves were performed. Patients were divided into four phenotypes according to their Warren-Yong and fibrosis scores: Mild calcification/fibrosis group, Severe calcification/fibrosis group, Predominant fibrosis group, Predominant calcification group. RESULTS: Among the 1,321 included patients, the vast majority (89%) has severe AS. Patients in the predominant fibrosis group, as compared to the predominant calcium group, were more often females (39 vs 31%, p=0.008), bicuspid valves (44 vs 34%, p=0.002) and they less often used ARBs (25 vs 30%, p=0.046). Female sex was independently associated with being in the predominant fibrosis group (OR 1.45 [95% CI 1.08-1.95], p=0.01), with a significant interaction between female sex and ARBs. Females taking ARBs compared to females not taking ARBs had significantly lower fibrosis score (p<0.001). This difference was not seen in males. CONCLUSION: In this large series of patients with moderate-severe AS, among females there was a negative association between intake of ARBs and valvular fibrosis. Thus, the possible effects of ARBs may be sex-specific, with a larger therapeutic role in females.

Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation.

There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of European ancestry. We report 32 genomic loci, among which 20 are novel. RNA sequencing of 500 human aortic valves highlights an enrichment in expression regulation at these loci and prioritizes candidate causal genes. Homozygous genotype for a risk variant near TWIST1, a gene involved in endothelial-mesenchymal transition, has a profound impact on aortic valve transcriptomics. We identify five genes outside of GWAS loci by combining a transcriptome-wide association study, colocalization, and Mendelian randomization analyses. Using cross-phenotype and phenome-wide approaches, we highlight the role of circulating lipoproteins, blood pressure and inflammation in the disease process. Our findings pave the way for the development of novel therapies for CAVS.

Do postoperative hemodynamic parameters add prognostic value for mortality after surgical aortic valve replacement?

Background: Although various hemodynamic parameters to assess prosthetic performance are available, prosthesis-patient mismatch (PPM) is defined exclusively by effective orifice area (EOA) index thresholds. Adjusting for the Society of Thoracic Surgeons predicted risk of mortality (STS PROM), we aimed to explore the added value of postoperative hemodynamic parameters for the prediction of all-cause mortality at 5 years after aortic valve replacement. Methods: Data were obtained from the Pericardial Surgical Aortic Valve Replacement (PERIGON) Pivotal Trial, a multicenter prospective cohort study examining the performance of the Avalus bioprosthesis. Candidate predictors were assessed at the first follow-up visit; patients who had no echocardiography data, withdrew consent, or died before this visit were excluded. Candidate predictors included peak jet velocity, mean pressure gradient, EOA, predicted and measured EOA index, Doppler velocity index, indexed internal prosthesis orifice area, and categories for PPM. The performance of Cox models was investigated using the c-statistic and net reclassification improvement (NRI), among other tools. Results: A total of 1118 patients received the study valve, of whom 1022 were eligible for the present analysis. In univariable analysis, STS PROM was the sole significant predictor of all-cause mortality (hazard ratio, 1.40; 95% confidence interval, 1.26-1.55). When extending the STS PROM with single hemodynamic parameters, neither the c-statistics nor the NRIs demonstrated added prognostic value compared to a model with STS PROM alone. Similar findings were observed when multiple hemodynamic parameters were added. Conclusions: The STS PROM was found to be the main predictor of patient prognosis. The additional prognostic value of postoperative hemodynamic parameters for the prediction of all-cause mortality was limited.

Outcomes of Total Aortic Arch Replacement in a Canadian Nationwide Registry.

BACKGROUND: Accurate benchmarking of outcomes after elective open total arch replacement is important for surgical decision making and for comparisons with emerging endovascular technologies. METHODS: A multicentre registry of consecutive aortic arch procedures in 9 centres across Canada contained 250 elective total arch replacements from 2010 to 2021. A total of 728 patients undergoing elective hemiarch replacement over the same time period was used as a comparator group. Propensity score matching was used to construct 202 well matched pairs. RESULTS: Patients undergoing total arch replacement were 63.2 ± 13.6 years old, and 34% were female. These patients were more likely to have connective tissue disorders compared with patients undergoing hemiarch replacement. When under hypothermic circulatory arrest, the total arch group uniformly used antegrade cerebral perfusion with median nadir temperature of 24°C (interquartile range [IQR] 21-25°C), and median duration 33 minutes (IQR 23-51 minutes). Before matching, in-hospital mortality and stroke rates were 5.2% and 10%, respectively, for the total arch group. After matching, the total arch group had in-hospital mortality similar to the hemiarch group (P = 0.58). Rates of stroke were also not statistically different (P = 0.11). The total arch group was more likely to experience delirium, prolonged intubation, increased intensive care unit length of stay, and transfusions. CONCLUSIONS: Elective total arch replacement is performed with good in-hospital mortality rates that are similar to rates after elective hemiarch repairs. However, total arch replacement was associated with significantly higher rates of other morbidities, including delirium and prolonged intubation.

Hemiarch versus extended arch repair for acute type A dissection: Results from a multicenter national registry.

OBJECTIVE: We compared perioperative outcomes of patients with acute type A aortic dissection undergoing hemiarch (HA) versus extended arch (EA) repair with or without descending aortic intervention. METHODS: Nine hundred twenty-nine patients underwent acute type A aortic dissection repair (2002-2021, 9 centers) including open distal repair (HA) with or without additional EA repair. EA with intervention on the descending aorta (EAD) included elephant trunk, antegrade thoracic endovascular aortic replacement, or uncovered dissection stent. EA with no descending intervention (EAND), included unstented suture-only methods. Primary outcomes were in-hospital mortality, permanent neurologic deficit, computed tomography malperfusion resolution, and a composite. Multivariable logistic regression was also performed. RESULTS: Mean age was 66 ± 18 years, 30% (278 out of 929) were women, and HA was performed more frequently (75% [n = 695]) than EA (25% [n = 234]). EAD techniques included: dissection stent (39 out of 234 [17%]), thoracic endovascular aortic replacement (18 out of 234 [7.7%]), and elephant trunk (87 out of 234 [37%]). In-hospital mortality (EA: n = 49 [21%] and HA: n = 129 [19%]; P = .42), and neurological deficit (EA: n = 43 [18%] and HA: n = 121 [17%]; P = .74) were similar. EA was not independently associated with death (EA vs HA odds ratio, 1.09; 95% CI, 0.77-1.54; P = .63) or neurologic deficit (EA vs HA odds ratio, 0.85; 95% CI, 0.47-1.55; P = .59). Composite adverse events differed significantly (EA vs HA odds ratio, 1.47; 95% CI, 1.16-1.87; P = .001). Malperfusion resolved more frequently after EAD (EAD: n = 32 [80%], EAND: n = 18 [56%], HA: n = 71 [50%]; P = .004), although multivariable analysis was not significant (EAD vs HA odds ratio, 2.17; 95% CI, 0.83-5.66; P = .10). CONCLUSIONS: Extended arch interventions pose similar perioperative mortality and neurologic risks as Hemiarch. Descending aortic reinforcement may promote malperfusion restoration. Extended techniques should be approached with caution in acute dissection due to increased risk of adverse events.

Association of Cerebral Oximetry With Brain Ischemic Lesions and Functional Outcomes in Arch Repair.

BACKGROUND: This exploratory analysis of the randomized controlled Aortic Surgery Cerebral Protection Evaluation CardioLink-3 trial sought to determine if cerebral oximetry desaturation during elective proximal arch repair is associated with detrimental postoperative neuroradiologic and neurofunctional outcomes. METHODS: Cerebral oximetry and pre- and postoperative brain magnetic resonance imaging data from 101 participants were analyzed. Oximetry data from the trial allocation groups were compared; the relationships between cerebral oximetry indices and new ischemic cerebral lesions on magnetic resonance imaging and neurologic outcomes were also evaluated. RESULTS: Total cerebral desaturation events (>20% decrease from baseline) on the left (median [interquartile range], 1 [1-3] vs 1.5 [0.5-3] with innominate and axillary cannulation; P = .80) were comparable to those on the right (1 [1-3] vs 1 [0-3]; P = .75) as were the total area under the curve of desaturation (left, P = .61; right, P = .84). Seventy patients had new ischemic lesions, among whom 36 had new severe lesions. Total desaturation events and area under the curve of desaturation were similar in patients with and without new ischemic lesions or severe lesions. The nadir regional cerebral saturation was lower on the left (49% [41-56]) than the right (53% [44-59]); left desaturation episodes were associated with lower postoperative cognitive test scores (P = .004). CONCLUSIONS: The innominate and axillary cannulation techniques for elective proximal arch repair with unilateral antegrade cerebral perfusion were associated with similar occurrences of cerebral oximetry desaturation and neither were associated with new ischemic lesions.

The Aortic Team Model and Collaborative Decision Pathways for the Management of Complex Aortic Disease: Clinical Practice Update From the Canadian Cardiovascular Society/Canadian Society of Cardiac Surgeons/Canadian Society for Vascular Surgery/Canadian Association for Interventional Radiology.

Disease of the aortic arch, descending thoracic, or thoracoabdominal aorta necessitates dedicated expertise across medical, endovascular, and surgical specialties. Cardiologists, cardiac surgeons, vascular surgeons, interventional radiologists, and others have expertise and skills that aid in the management of patients with complex aortic disease. No specialty is uniformly expert in all aspects of required care. Because of this dispersion of expertise across specialties, an aortic team model approach to decision-making and treatment is advocated. A nonhierarchical partnership across specialties within an interdisciplinary aortic clinic ensures that all treatment options are considered and promotes shared decision-making between the patient and all aortic experts. Furthermore, regionalization of care for aortic disease of increased complexity assures that the breadth of treatment options is available and that favourable volume-outcome ratios for high-risk procedures are maintained. An awareness of best practice care pathways for patient referrals for preventative management, acute care scenarios, chronic care scenarios, and pregnancy might facilitate a more organized management schema for aortic disease across Canada and improve lifelong surveillance initiatives.

Mid-term outcomes of the COMMENCE trial investigating mitral valve replacement using a bioprosthesis with a novel tissue.

Objective: Novel tissue leaflets (RESILIA tissue) may improve durability of bioprosthetic heart valves. The COMMENCE trial is an ongoing prospective study to evaluate valve replacement using RESILIA tissue. This report describes mid-term outcomes in the mitral cohort of COMMENCE. Methods: Adult patients requiring mitral valve replacement were enrolled in a prospective, single-arm trial at 17 sites in the United States and Canada. An independent clinical events committee adjudicated safety events using definitions from established guidelines, and hemodynamic performance was evaluated by an independent echocardiographic core laboratory. Results: Eighty-two patients (median age 70 years) successfully underwent mitral valve replacement with the study valve. Five-year event-free probabilities for all-cause mortality, structural valve deterioration, and reoperation were 79.9%, 98.7%, and 97.1%, respectively. Hemodynamic valve function measurements were stable through the 5-year follow-up period; valvular leaks were infrequently observed and primarily clinically insignificant/mild. Conclusions: Mitral valve replacement patients implanted with a RESILIA tissue bioprosthesis had a good safety profile and clinically stable hemodynamic performance.

Hybrid Treatment of Complex Diseases of the Aortic Arch and Descending Thoracic Aorta by Frozen Elephant Trunk Technique.

The surgical management of acute and chronic complex diseases involving the aortic arch and the descending thoracic aorta remains challenging. Hybrid procedures associating total open arch replacement and stent-grafting of the proximal descending aorta were developed to allow a potential single-stage treatment, promote remodeling of the downstream aorta, and facilitate a potential second-stage thoracic endovascular aortic repair by providing an ideal landing zone. While these approaches initially used various homemade combinations of available conventional prostheses and stent-grafts, the so-called frozen elephant trunk technique emerged with the development of several custom-made hybrid prostheses. The aim of this study was to review the contemporary outcomes of this technique in the management of complex aortic diseases, with a special focus on procedural planning, organ protection and monitoring, refinements in surgical techniques, and long-term follow-up.

Durability of bioprosthetic aortic valve replacement in patients under the age of 60 years - 1-year follow-up from the prospective INDURE registry.

OBJECTIVES: We report 1-year safety and clinical outcomes in patients <60 years undergoing bioprosthetic surgical aortic valve intervention. METHODS: The INSPIRIS RESILIA Durability Registry is a prospective, multicentre registry to assess clinical outcomes of patients <60 years. Patients with planned SAVR with or without concomitant replacement of the ascending aorta and/or coronary bypass surgery were included. Time-related valve safety, haemodynamic performance and quality of life (QoL) at 1 year were assessed. RESULTS: A total of 421 patients were documented with a mean age of 53.5 years, 76.5% being male and 27.2% in NYHA class III/IV. Outcomes within 30 days included cardiovascular-related mortality (0.7%), time-related valve safety (VARC-2; 5.8%), thromboembolic events (1.7%), valve-related life-threatening bleeding (VARC-2; 4.3%) and permanent pacemaker implantation (3.8%). QoL was significantly increased at 6 months and sustained at 1 year. Freedom from all-cause mortality at 1 year was 98.3% (95% confidence interval 97.1; 99.6) and 81.8% were NYHA I versus 21.9% at baseline. No patient developed structural valve deterioration stage 3 (VARC-3). The mean aortic pressure gradient was 12.6 mmHg at 1 year and the effective orifice area was 1.9 cm2. CONCLUSIONS: The 1-year data from the INSPIRIS RESILIA valve demonstrate good safety and excellent haemodynamic performance as well as an early QoL improvement. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT03666741.

Percutaneous Transcatheter Edge-to-Edge Mitral Valve Repair With MitraClip System in the Era of G4.

The use of transcatheter edge-to-edge mitral valve repair (TEER) in symptomatic patients with severe mitral regurgitation (MR) has dramatically increased over the last few years. Current guidelines consider TEER as a reasonable option in symptomatic patients with primary or chronic secondary severe MR with high or prohibitive surgical risk and favorable anatomy. However, several anatomical and morphological mitral features have restricted the use of this mini-invasive technique in its early experience. The latest fourth generation (G4) of the MitraClip system has been recently introduced and includes the possibility of independent leaflet grasping and 4 different sizes. This technical update offers the possibility of selecting and combining multiple devices for complex mitral valve anatomies and challenging procedures, which helps expand the applications of TEER. The present review describes the potential advantages and the help of the MitraClip G4 devices to overcome various anatomic and morphologic issues in challenging cases with complex primary and secondary MR procedures.

Pledgeted versus nonpledgeted sutures in aortic valve replacement: Insights from a prospective multicenter trial.

Objective: The objective of this study was to compare short- and midterm clinical and echocardiographic outcomes according to the use of pledgeted sutures during aortic valve replacement. Methods: Patients with aortic stenosis or regurgitation requiring aortic valve replacement were enrolled in a prospective cohort study to evaluate the safety of a new stented bioprosthesis. Outcomes were analyzed according to the use of pledgets (pledgeted group) or no pledgets (nonpledgeted group). The primary outcome was a composite of thromboembolism, endocarditis, and major paravalvular leak at 5 years of follow-up. Secondary outcomes included multiple clinical endpoints and hemodynamic outcomes. Propensity score matching was performed to adjust for prognostic factors, and subanalyses with small valve sizes (<23 mm) and suturing techniques were performed. Results: The pledgeted group comprised 640 patients (59%), and the nonpledgeted group 442 (41%), with baseline discrepancies in demographic characteristics, comorbidities, and stenosis severity. There were no differences between groups in any outcome. After propensity score matching, the primary outcome occurred in 41 (11.7%) patients in the pledgeted and 36 (9.8%) in the nonpledgeted group (P = .51). The effective orifice area was smaller in the pledgeted group (P = .045), whereas no difference was observed for the mean or peak pressure gradient. Separate subanalyses with small valve sizes and suturing techniques did not show relevant differences. Conclusions: In this large propensity score-matched cohort, comprehensive clinical outcomes were comparable between patients who underwent aortic valve replacement with pledgeted and nonpledgeted sutures up to 5 years of follow-up, but pledgets might lead to a slightly smaller effective orifice area in the long run.

Low-Dose vs Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Trial.

BACKGROUND: Current guidelines recommend a target international normalized ratio (INR) range of 2.5 to 3.5 in patients with a mechanical mitral prosthesis. The Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) Mitral randomized controlled noninferiority trial assessed safety and efficacy of warfarin at doses lower than currently recommended in patients with an On-X (Artivion, Inc) mechanical mitral valve. METHODS: After On-X mechanical mitral valve replacement, followed by at least 3 months of standard anticoagulation, 401 patients at 44 North American centers were randomized to low-dose warfarin (target INR, 2.0-2.5) or standard-dose warfarin (target INR, 2.5-3.5). All patients were prescribed aspirin, 81 mg daily, and encouraged to use home INR testing. The primary end point was the sum of the linearized rates of thromboembolism, valve thrombosis, and bleeding events. The design was based on an expected 7.3% event rate and 1.5% noninferiority margin. RESULTS: Mean patient follow-up was 4.1 years. Mean INR was 2.47 and 2.92 (P <.001) in the low-dose and standard-dose warfarin groups, respectively. Primary end point rates were 11.9% per patient-year in the low-dose group and 12.0% per patient-year in the standard-dose group (difference, -0.07%; 95% CI, -3.40% to 3.26%). The CI >1.5%, thus noninferiority was not achieved. Rates (percentage per patient-year) of the individual components of the primary end point were 2.3% vs 2.5% for thromboembolism, 0.5% vs 0.5% for valve thrombosis, and 9.13% vs 9.04% for bleeding. CONCLUSIONS: Compared with standard-dose warfarin, low-dose warfarin did not achieve noninferiority for the composite primary end point. (PROACT Clinicaltrials.gov number, NCT00291525).

Knowledge, attitudes, and practice preferences in the surgical threshold for ascending aortic aneurysm among Canadian cardiac surgeons.

OBJECTIVE: The survey aimed to assess the practice patterns of Canadian cardiac surgeons on the size threshold at which patients with ascending aortic aneurysm would be offered surgery. METHODS: A 18-question electronic survey was electronically distributed to 148 practicing cardiac surgeons in Canada via email from January to August 2020. Questions presented clinical scenarios focusing on modifying a single variable, and respondents were asked to identify their surgical size threshold for each of the clinical scenarios. RESULTS: The individual response rate was 62.0% (91/148) and institutional response rate was 89.3% (25/29). For an incidental asymptomatic ascending aortic aneurysm in a 60-year-old otherwise-healthy male patient with a tricuspid aortic valve and bicuspid aortic valve of 1.9 m2, 20.2% of the respondents would recommend surgery when the aneurysm was <5.5 cm. A significant number of surgeons modified their surgical threshold in response to changes to BSA, bicuspid aortic valve, growth rate, age, occupation, symptom, and family history (P < .01). Notably, if the patient had a bicuspid aortic valve, 41.0% of respondents lowered their threshold for surgery, with only 43.0% recommending surgery at ≥5.5 cm (P < .01). CONCLUSIONS: Practice variations exist in the current size threshold for surgery of ascending aortic aneurysms in Canada. These differences between surgeons are further accentuated in the context of bicuspid aortic valve, smaller body stature, younger age, low growth rate, family history, and for the performance of isometric exercise. These represent important areas where future prospective studies are required to inform best practice.