Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

Conduction Disturbances and Outcome After Surgical Aortic Valve Replacement in Patients With Bicuspid and Tricuspid Aortic Stenosis.

BACKGROUND: This study aimed to compare the incidence and prognostic implications of new-onset conduction disturbances after surgical aortic valve replacement (SAVR) in patients with bicuspid aortic valve (BAV) aortic stenosis (AS) versus patients with tricuspid aortic valve (TAV) AS (ie, BAV-AS and TAV-AS, respectively). Additionally, the study included stratification of BAV patients according to subtype. METHODS: In this cohort study, the incidence of postoperative third-degree atrioventricular (AV) block with subsequent permanent pacemaker requirement and new-onset left bundle-branch block (LBBB) was investigated in 1147 consecutive patients without preoperative conduction disorder who underwent isolated SAVR (with or without ascending aortic surgery) between January 1, 2005, and December 31, 2022. The groups were stratified by aortic valve morphology (BAV, n=589; TAV, n=558). The outcomes of interests were new-onset third-degree AV block or new-onset LBBB during the index hospitalization. The impact of new-onset postoperative conduction disturbances on survival was investigated in BAV-AS and TAV-AS patients during a median follow-up of 8.2 years. BAV morphology was further categorized according to the Sievers and Schmidtke classification system (possible in 307 BAV-AS patients) to explore association between BAV subtypes and new-onset conduction disturbances after SAVR. RESULTS: The overall incidence of third-degree AV block and new-onset LBBB after SAVR was 4.5% and 7.8%, respectively. BAV-AS patients had a higher incidence of both new-onset third-degree AV block (6.5% versus 2.5%; P=0.001) and new-onset LBBB (9.7% versus 5.7%; P=0.013) compared with TAV-AS patients. New-onset LBBB was associated with an increased all-cause mortality during follow-up (adjusted hazard ratio, 1.60 [95% CI, 1.12-2.30]; P=0.011), whereas new-onset third-degree AV block was not associated with worse prognosis. Subgroup analysis of the BAV cohort revealed that BAV-AS patients with fusion of the right- and non-coronary cusps had the highest risk of new-onset third-degree AV block (adjusted odds ratio [aOR], 8.33 [95% CI, 3.31-20.97]; P<0.001, with TAV as reference group) and new-onset LBBB (aOR, 4.03 [95% CI, 1.84-8.82]; P<0.001, with TAV as reference group), whereas no significant association was observed for the other BAV subtypes. CONCLUSIONS: New-onset LBBB after SAVR is associated with increased all-cause mortality during follow-up, and is more frequent complication in BAV AS patients compared with TAV-AS patients. BAV-AS patients with fusion of the right- and non-coronary cusps have an increased risk for conduction disturbances after SAVR. This should be taken into consideration when managing these patients.

Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association.

Valvular heart disease is a common cause of morbidity and mortality worldwide and has no effective medical therapy. Severe disease is managed with valve replacement procedures, which entail high health care-related costs and postprocedural morbidity and mortality. Robust ongoing research programs have elucidated many important molecular pathways contributing to primary valvular heart disease. However, there remain several key challenges inherent in translating research on valvular heart disease to viable molecular targets that can progress through the clinical trials pathway and effectively prevent or modify the course of these common conditions. In this scientific statement, we review the basic cellular structures of the human heart valves and discuss how these structures change in primary valvular heart disease. We focus on the most common primary valvular heart diseases, including calcific aortic stenosis, bicuspid aortic valves, mitral valve prolapse, and rheumatic heart disease, and outline the fundamental molecular discoveries contributing to each. We further outline potential therapeutic molecular targets for primary valvular heart disease and discuss key knowledge gaps that might serve as future research priorities.

Cardiovascular Management of Aortopathy in Children: A Scientific Statement From the American Heart Association.

Aortopathy encompasses a spectrum of conditions predisposing to dilation, aneurysm, dissection, or rupture of the aorta and other blood vessels. Aortopathy is diagnosed commonly in children, from infancy through adolescence, primarily affecting the thoracic aorta, with variable involvement of the peripheral vasculature. Pathogeneses include connective tissue disorders, smooth muscle contraction disorders, and congenital heart disease, including bicuspid aortic valve, among others. The American Heart Association has published guidelines for diagnosis and management of thoracic aortic disease. However, these guidelines are predominantly focused on adults and cannot be applied adeptly to growing children with emerging features, growth and developmental changes, including puberty, and different risk profiles compared with adults. Management to reduce risk of progressive aortic dilation and dissection or rupture in children is complex and involves genetic testing, cardiovascular imaging, medical therapy, lifestyle modifications, and surgical guidance that differ in many ways from adult management. Pediatric practice varies widely, likely because aortopathy is pathogenically heterogeneous, including genetic and nongenetic conditions, and there is limited published evidence to guide care in children. To optimize care and reduce variation in management, experts in pediatric aortopathy convened to generate this scientific statement regarding the cardiovascular care of children with aortopathy. Available evidence and expert consensus were combined to create this scientific statement. The most common causes of pediatric aortopathy are reviewed. This document provides a general framework for cardiovascular management of aortopathy in children, while allowing for modification based on the personal and familial characteristics of each child and family.

Valvular Heart Disease: New Concepts in Pathophysiology and Therapeutic Approaches.

This review discusses recent advancements in the field of valvular heart disease. Topics covered include recognition of the impact of atrial fibrillation on development and assessment of valvular disease, strategies for global prevention of rheumatic heart disease, understanding and management of secondary mitral regurgitation, the updated classification of bicuspid aortic valve disease, recognition of heightened cardiovascular risk associated with moderate aortic stenosis, and a growing armamentarium of transcatheter therapies.

Familial Associations of Prevalence and Cause-Specific Mortality for Thoracic Aortic Disease and Bicuspid Aortic Valve in a Large-Population Database.

BACKGROUND: Thoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database. METHODS: In this observational case-control study of the Utah Population Database, we identified probands with a diagnosis of BAV, thoracic aortic aneurysm, or thoracic aortic dissection. Age- and sex-matched controls (10:1 ratio) were identified for each proband. First-degree relatives, second-degree relatives, and first cousins of probands and controls were identified through linked genealogical information. Cox proportional hazard models were used to quantify the familial associations for each diagnosis. We used a competing-risk model to determine the risk of cardiovascular-specific and aortic-specific mortality for relatives of probands. RESULTS: The study population included 3 812 588 unique individuals. Familial hazard risk of a concordant diagnosis was elevated in the following populations compared with controls: first-degree relatives of patients with BAV (hazard ratio [HR], 6.88 [95% CI, 5.62-8.43]); first-degree relatives of patients with thoracic aortic aneurysm (HR, 5.09 [95% CI, 3.80-6.82]); and first-degree relatives of patients with thoracic aortic dissection (HR, 4.15 [95% CI, 3.25-5.31]). In addition, the risk of aortic dissection was higher in first-degree relatives of patients with BAV (HR, 3.63 [95% CI, 2.68-4.91]) and in first-degree relatives of patients with thoracic aneurysm (HR, 3.89 [95% CI, 2.93-5.18]) compared with controls. Dissection risk was highest in first-degree relatives of patients who carried a diagnosis of both BAV and aneurysm (HR, 6.13 [95% CI, 2.82-13.33]). First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection had a higher risk of aortic-specific mortality (HR, 2.83 [95% CI, 2.44-3.29]) compared with controls. CONCLUSIONS: Our results indicate that BAV and thoracic aortic disease carry a significant familial association for concordant disease and aortic dissection. The pattern of familiality is consistent with a genetic cause of disease. Furthermore, we observed higher risk of aortic-specific mortality in relatives of individuals with these diagnoses. This study provides supportive evidence for screening in relatives of patients with BAV, thoracic aneurysm, or dissection.

Identification of congenital aortic valve malformations in juvenile natriuretic peptide receptor 2-deficient mice using high-frequency ultrasound.

Mouse models of congenital aortic valve malformations are useful for studying disease pathobiology, but most models have incomplete penetrance [e.g., ∼2 to 77% prevalence of bicuspid aortic valves (BAVs) across multiple models]. For longitudinal studies of pathologies associated with BAVs and other congenital valve malformations, which manifest over months in mice, it is operationally inefficient, economically burdensome, and ethically challenging to enroll large numbers of mice in studies without first identifying those with valvular abnormalities. To address this need, we established and validated a novel in vivo high-frequency (30 MHz) ultrasound imaging protocol capable of detecting aortic valvular malformations in juvenile mice. Fifty natriuretic peptide receptor 2 heterozygous mice on a low-density lipoprotein receptor-deficient background (Npr2+/-;Ldlr-/-; 32 males and 18 females) were imaged at 4 and 8 wk of age. Fourteen percent of the Npr2+/-;Ldlr-/- mice exhibited features associated with aortic valve malformations, including 1) abnormal transaortic flow patterns on color Doppler (recirculation and regurgitation), 2) peak systolic flow velocities distal to the aortic valves reaching or surpassing ∼1,250 mm/s by pulsed-wave Doppler, and 3) putative fusion of cusps along commissures and abnormal movement elucidated by two-dimensional (2-D) imaging with ultrahigh temporal resolution. Valves with these features were confirmed by ex vivo gross anatomy and histological visualization to have thickened cusps, partial fusions, or Sievers type-0 bicuspid valves. This ultrasound imaging protocol will enable efficient, cost effective, and humane implementation of studies of congenital aortic valvular abnormalities and associated pathologies in a wide range of mouse models.NEW & NOTEWORTHY We developed a high-frequency ultrasound imaging protocol for diagnosing congenital aortic valve structural abnormalities in 4-wk-old mice. Our protocol defines specific criteria to distinguish mice with abnormal aortic valves from those with normal tricuspid valves using color Doppler, pulsed-wave Doppler, and two-dimensional (2-D) imaging with ultrahigh temporal resolution. This approach enables early identification of valvular abnormalities for efficient and ethical experimental design of longitudinal studies of congenital valve diseases and associated pathologies in mice.

Patients With Bicuspid Aortic Stenosis Demonstrate Adverse Left Ventricular Remodeling and Impaired Cardiac Function Before Surgery With Increased Risk of Postoperative Heart Failure.

BACKGROUND: Differences in adverse cardiac remodeling between patients who have bicuspid (BAV) and tricuspid aortic valve (TAV) with severe isolated aortic stenosis (AS) and its prognostic impact after surgical aortic valve replacement remains unclear. We sought to investigate differences in preoperative diastolic and systolic function in patients with BAV and TAV who have severe isolated AS and the incidence of postoperative heart failure hospitalization and mortality. METHODS: Two hundred seventy-one patients with BAV (n=152) or TAV (n=119) and severe isolated AS without coronary artery disease or other valvular heart disease, scheduled for surgical aortic valve replacement, were prospectively included. Comprehensive preoperative echocardiographic assessment of left ventricular (LV) diastolic and systolic function was performed. The heart failure events were registered during a mean prospective follow-up of 1260 days versus 1441 days for patients with BAV or TAV, respectively. RESULTS: Patients with BAV had a more pronounced LV hypertrophy with significantly higher indexed LV mass ([LVMi] 134 g/m2 versus 104 g/m2, P<0.001), higher prevalence of LV diastolic dysfunction (72% versus 44%, P<0.001), reduced LV ejection fraction (55% versus 60%, P<0.001), significantly impaired global longitudinal strain (P<0.001), significantly higher NT-proBNP (N-terminal pro-brain natriuretic peptide) levels (P=0.007), and a higher prevalence of preoperative levosimendan treatment (P<0.001) than patients with TAV. LVMi was associated with diastolic dysfunction in both patients with BAV and TAV. There was a significant interaction between aortic valve morphology and LVMi on LV ejection fraction, which indicated a pronounced association between LVMi and LV ejection fraction for patients with BAV and lack of association between LVMi and LV ejection fraction for patients with TAV. Postoperatively, the patients with BAV required significantly more inotropic support (P<0.001). The patients with BAV had a higher cumulative incidence of postoperative heart failure admissions compared with patients with TAV (28.2% versus 10.6% at 6 years after aortic valve replacement, log-rank P=0.004). Survival was not different between patients with BAV and TAV (log-rank P=0.165). CONCLUSIONS: Although they were significantly younger, patients with BAV who had isolated severe AS had worse preoperative LV function and an increased risk of postoperative heart failure hospitalization compared with patients who had TAV. Our findings suggest that patients who have BAV with AS might benefit from closer surveillance and possibly earlier intervention.

Genetic and Developmental Contributors to Aortic Stenosis.

Aortic stenosis (AS) remains one of the most common forms of valve disease, with significant impact on patient survival. The disease is characterized by left ventricular outflow obstruction and encompasses a series of stenotic lesions starting from the left ventricular outflow tract to the descending aorta. Obstructions may be subvalvar, valvar, or supravalvar and can be present at birth (congenital) or acquired later in life. Bicuspid aortic valve, whereby the aortic valve forms with two instead of three cusps, is the most common cause of AS in younger patients due to primary anatomic narrowing of the valve. In addition, the secondary onset of premature calcification, likely induced by altered hemodynamics, further obstructs left ventricular outflow in bicuspid aortic valve patients. In adults, degenerative AS involves progressive calcification of an anatomically normal, tricuspid aortic valve and is attributed to lifelong exposure to multifactoral risk factors and physiological wear-and-tear that negatively impacts valve structure-function relationships. AS continues to be the most frequent valvular disease that requires intervention, and aortic valve replacement is the standard treatment for patients with severe or symptomatic AS. While the positive impacts of surgical interventions are well documented, the financial burden, the potential need for repeated procedures, and operative risks are substantial. In addition, the clinical management of asymptomatic patients remains controversial. Therefore, there is a critical need to develop alternative approaches to prevent the progression of left ventricular outflow obstruction, especially in valvar lesions. This review summarizes our current understandings of AS cause; beginning with developmental origins of congenital valve disease, and leading into the multifactorial nature of AS in the adult population.

Transcatheter Aortic Valve Replacement in Bicuspid Aortic Valve Stenosis.

After 15 years of successive randomized, controlled trials, indications for transcatheter aortic valve replacement (TAVR) are rapidly expanding. In the coming years, this procedure could become the first line treatment for patients with a symptomatic severe aortic stenosis and a tricuspid aortic valve anatomy. However, randomized, controlled trials have excluded bicuspid aortic valve (BAV), which is the most frequent congenital heart disease occurring in 1% to 2% of the total population and representing at least 25% of patients 80 years of age or older referred for aortic valve replacement. The use of a less invasive transcatheter therapy in this elderly population became rapidly attractive, and approximately 10% of patients currently undergoing TAVR have a BAV. The U.S. Food and Drug Administration and the "European Conformity" have approved TAVR for low-risk patients regardless of the aortic valve anatomy whereas international guidelines recommend surgical replacement in BAV populations. Given this progressive expansion of TAVR toward younger and lower-risk patients, heart teams are encountering BAV patients more frequently, while the ability of this therapy to treat such a challenging anatomy remains uncertain. This review will address the singularity of BAV anatomy and associated technical challenges for the TAVR procedure. We will examine and summarize available clinical evidence and highlight critical knowledge gaps regarding TAVR utilization in BAV patients. We will provide a comprehensive overview of the role of computed tomography scans in the diagnosis, and classification of BAV and TAVR procedure planning. Overall, we will offer an integrated framework for understanding the current role of TAVR in the treatment of bicuspid aortic stenosis and for guiding physicians in clinical decision-making.

Update on supra-annular sizing of transcatheter aortic valve prostheses in raphe-type bicuspid aortic valve disease according to the LIRA method.

Recent evidence has shown that transcatheter heart valve (THV) anchoring in bicuspid aortic valve (BAV) patients occurs at the level of the raphe, known as the LIRA (Level of Implantation at the RAphe) plane. Our previous work in a cohort of 20 patients has shown that the delineation of the perimeter and device sizing at this level is associated with optimal procedural outcome. The goals of this study were to confirm the feasibility of this method, evaluate 30-day outcomes of LIRA sizing in a larger cohort of patients, assess interobserver variation and reproducibility of this sizing methodology, and analyse the interaction of LIRA-sized prostheses with the surrounding anatomy. The LIRA sizing method was applied to consecutive patients presenting to our centre with raphe-type BAV disease between November 2018 and October 2021. Supra-annular self-expanding THVs were sized based on baseline CT scan perimeters at the LIRA plane and the virtual basal ring. In cases where there was discrepancy between the two measurements, the plane with the smallest perimeter was considered the reference for prosthesis sizing. Post-procedural device success, defined according to Valve Academic Research Consortium-2 (VARC-2) criteria, was evaluated in the overall cohort. A total of 50 patients (mean age 80 ± 6 years, 70% male) with raphe-type BAV disease underwent transcatheter aortic valve replacement (TAVR) using different THV prostheses. The LIRA plane method appeared to be highly successful (100% VARC-2 device success) with no procedural mortality, no valve migration, no moderate-severe paravalvular leak, and low transprosthetic gradients (residual mean gradient 8.2 ± 3.4 mmHg). There were no strokes, no in-hospital or 30-day mortality, and an incidence of in-hospital pacemaker implantation of 10%. Furthermore, measurement of the LIRA plane perimeter was highly reproducible between observers (r = 0.980; P < 0.001) and predictive of the post-procedural prosthetic valve perimeter on CT scanning (r = 0.981; P < 0.001). We confirm the feasibility of supra-annular sizing using the LIRA method in a large cohort of patients with high procedural success and good clinical outcomes at 30 days. Application of the LIRA method optimizes THV prosthesis sizing in patients with raphe-type BAV disease.

Immediate and late outcomes of transcatheter aortic valve implantation versus surgical aortic valve replacement in bicuspid valves: Meta-analysis of reconstructed time-to-event data.

BACKGROUND: Outcomes of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) in patients with aortic stenosis and bicuspid aortic valve (BAV) must be better investigated. METHODS: A meta-analysis including studies published by January 2022 reporting immediate outcomes (in-hospital death, stroke, acute kidney injury [AKI], major bleeding, new permanent pacemaker implantation [PPI], paravalvular leakage [PVL]), mortality in the follow-up (with Kaplan-Meier curves for reconstruction of individual patient data). RESULTS: Five studies met our eligibility criteria. No statistically significant difference was observed for in-hospital death, stroke, AKI, and PVL. TAVI was associated with lower risk of major bleeding (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.12-0.69; p = .025), but higher risk of PPI (OR: 2.00; 95% CI: 1.05-3.77; p = .041). In the follow-up, mortality after TAVI was significantly higher in the analysis with the largest samples (HR: 1.24, 95% CI: 1.01-1.53, p = .043), but no statistically significant difference was observed with risk-adjusted populations (HR: 1.06, 95% CI: 0.86-1.32, p = .57). Landmark analyses suggested a time-varying risk with TAVI after 10 and 13 months in both largest and risk-adjusted populations (HR: 2.13, 95% CI: 1.45-3.12, p < .001; HR: 1.7, 95% CI: 1.11-2.61, p = .015, respectively). CONCLUSION: Considering the immediate outcomes and comparable overall survival observed in risk-adjusted populations, TAVI can be used safely in selected BAV patients. However, a time-varying risk is present (favoring SAVR over TAVI at a later timepoint). This finding was likely driven by higher rates of PPI with TAVI.

Dilatation and Dysfunction of the Neo-aortic Root and in 76 Patients After the Ross Procedure.

Pulmonary autograft replacement (Ross procedure) is used as an alternative to prosthetic aortic valve replacement patients with aortic valve disease. There are limited data on incidence and risk factors for dilatation and dysfunction of the neo-aortic after the Ross procedure. Ross procedure was performed in 100 patients at our institution between 1993 and 2011. In 76 patients, complete follow-up data were available. Their median age at surgery was 16 (0.4-58) years (76 % males; 95 % with congenital aortic valve disease). Median follow-up duration was 5.2 years (0.3-16.0 years). We analyzed their clinical and echocardiographic follow-up to identify possible risk factors for neo-aortic root dilatation and dysfunction. Ross procedure included reduction plasty of the native ascending aorta in 25 % of patients. During follow-up, 21 patients (28 %) developed neo-aortic root dilatation, 38 patients (50 %) dilatation oft the native ascending aorta and 7 patients (9 %) at least moderate neo-aortic regurgitation. Univariate risk factors for neo-aortic root dilatation were preoperative aortic regurgitation (p = 0.04), concomitant reduction plasty of the ascending aorta (p = 0.009) and a longer duration of follow-up (p = 0.005). Younger age at surgery was associated with dilatation of the ascending aorta (p = 0.03). Reoperation on the neo-aortic root because of severe dilatation was necessary in 6 patients (8 %), where 2 patients had at least moderate neo-aortic root regurgitation. Neo-aortic root and aortic dilatation are common after the Ross procedure. This is often combined with neo-aortic valve dysfunction. Close follow-up of these patients is mandatory.

3D Characterization of the Aortic Valve and Aortic Arch in Bicuspid Aortic Valve Patients.

Patients with bicuspid aortic valve (BAV) commonly have associated aortic stenosis and aortopathy. The geometry of the aortic arch and BAV is not well defined quantitatively, which makes clinical classifications subjective or reliant on limited 2D measurements. The goal of this study was to characterize the 3D geometry of the aortic arch and BAV using objective and quantitative techniques. Pre-TAVR computed tomography angiogram (CTA) in patients with BAV and aortic stenosis (AS) were analyzed (n = 59) by assessing valve commissural angle, presence of a fused region, percent of fusion, and calcium volume. The ascending aorta and aortic arch were reconstructed from patient-specific imaging segmentation to generate a centerline and calculate maximum curvature and maximum area change for the ascending aorta and the descending aorta. Aortic valve commissural angle signified a bimodal distribution suggesting tricuspid-like (≤ 150°, 52.5% of patients) and bicuspid-like (> 150°, 47.5%) morphologies. Tricuspid like was further classified by partial (10.2%) or full (42.4%) fusion, and bicuspid like was further classified into valves with fused region (27.1%) or no fused region (20.3%). Qualitatively, the aortic arch was found to have complex patient-specific variations in its 3D shape with some showing extreme diameter changes and kinks. Quantitatively, subgroups were established using maximum curvature threshold of 0.04 and maximum area change of 30% independently for the ascending and descending aorta. These findings provide insight into the geometric structure of the aortic valve and aortic arch in patients presenting with BAV and AS where 3D characterization allows for quantitative classification of these complex anatomic structures.

Impact of Pacemaker Implantation After Transcatheter Aortic Valve Replacement on Long-Term Survival in Patients With Bicuspid Aortic Valve.

Limited data are available about the impact of permanent pacemaker (PPM) implantation on long-term survival in patients with a bicuspid aortic valve (BAV) and severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR). We aimed to evaluate the long-term clinical outcomes of patients with BAV with AS who underwent periprocedural PPM implantation after TAVR with a self-expandable prosthesis. Data from patients with BAV and severe AS who underwent TAVR between April 2009 and January 2022 and followed in the framework of the One Hospital ClinicalService-CoreValve Project were collected. Patients were categorized in 2 groups according to PPM implantation after TAVR ("PPM" group) or not ("no PPM" group). The coprimary end points were all-cause death and a composite of cardiac mortality, rehospitalization because of cardiac causes, stroke, and myocardial infarction. Overall, 106 patients were considered (74 in the "no PPM" group and 32 in the "PPM" group). No statistically significant difference was found between the groups in terms of follow-up and baseline characteristics. Patients in the PPM group were more likely to show baseline conduction abnormalities (p = 0.023). Patients in the PPM group were more often treated with older generation prosthesis than those in the no PPM group (28.1% vs 5.4%, respectively, p = 0.013). At 2 years of follow-up, all-cause death in the no PPM and PPM groups occurred in 20.0% and 10.0% of patients, respectively (hazard ratio 0.37, 95% confidence interval 0.08 to 1.67). Similarly, no difference was evident for the composite end point between the 2 groups (no PPM vs PPM: 8 [14.6%] vs 6 [19.3%], hazard ratio 1.67, 95% CI 0.58 to 4.81). In conclusion, patients with severe AS and BAV treated with TAVR complicated by PPM implantation are not exposed to an increased risk of major adverse events at 2 years of follow-up.

Associations of Lifelong Exercise Characteristics With Valvular Function and Aortic Diameters in Patients With a Bicuspid Aortic Valve.

BACKGROUND: The potential impact of exercise on valvular function and aortic diameters in patients with a bicuspid aortic valve remains unclear. Therefore, we assessed the association between lifelong exercise characteristics, valvular dysfunction, and aortic dilatation in patients with a bicuspid aortic valve. METHODS AND RESULTS: In this cross-sectional study, exercise volume (metabolic equivalent of task minutes per week), exercise intensity, and sport type were determined from the age of 12 years to participation using a validated questionnaire. Echocardiography was used to assess aortic stenosis or aortic regurgitation and to measure diameters at the sinuses of Valsalva and ascending aorta. Aortic dilatation was defined as a Z-score ≥2. Four hundred and seven patients (42±17 years, 60% men) were included, of which 133 were sedentary (<500 metabolic equivalent of task minutes per week), 94 active (500-1000 metabolic equivalent of task minutes per week), and 180 highly active (≥1000 metabolic equivalent of task minutes per week). Moderate-to-severe aortic stenosis or aortic regurgitation was present in 23.7% and 20.0%, respectively. Sinuses of Valsalva and ascending aorta diameters were 34.8±6.6 and 36.5±8.1 mm, whereas aortic dilatation was found in 21.6% and 53.4%, respectively. Exercise volume was not associated with valve dysfunction or aortic dilatation. Vigorous intensity and mixed sports were associated with a lower prevalence of aortic stenosis (adjusted odds ratios, 0.43 [0.20-0.94] and adjusted odds ratios, 0.47 [0.23-0.95]). Exercise intensity and sport type were not associated with aortic regurgitation and aortic dilatation. CONCLUSIONS: We found no deleterious associations between lifelong exercise characteristics, valvular dysfunction, and aortic dilatation in patients with a bicuspid aortic valve. Vigorous intensity and exercise in mixed sports were associated with a lower prevalence of moderate-to-severe aortic stenosis. These observations suggest that lifelong exercise does not appear to induce adverse cardiovascular effects in patients with a bicuspid aortic valve.

Trichinellosis-Induced Eosinophilic Myocarditis Mimicking Hypereosinophilic Syndrome.

Trichinella spiralisis an uncommon parasitic disease contracted through the consumption of undercooked pork. We report the case of a 59-year-old man with a history of bicuspid aortic valve with recent travel to the Philippines and consumption of raw pork presenting with progressive myalgia and hypereosinophilia (nadir 12,940/uL) in profound cardiogenic shock in the setting of critical aortic stenosis. He underwent emergent balloon valvuloplasty, which was complicated by aortic insufficiency. This necessitated a transcatheter aortic valve replacement. However, despite hemodynamic stabilization, he developed catastrophic eosinophilic myocarditis, complicated by cardiac arrest from ventricular tachycardia. A rectus femoris muscle biopsy confirmed the diagnosis, showing a T. spiralis parasite and significant eosinophilic infiltration. Empiric treatment with albendazole, ivermectin, and methylprednisolone resulted in the significant resolution of symptoms and the liberalization of critical illness. This case highlights the challenges of diagnosing the underlying etiologies of hypereosinophilia and/or eosinophilic myocarditis, underscoring the importance of considering parasitic etiologies, particularly in endemic regions or in patients who have a significant travel history to such areas. Prompt diagnosis and treatment are essential to prevent morbidity and mortality.

Flow quantification within the aortic ejection tract using 4D flow cardiac MRI in patients with bicuspid aortic valve: Implications for the assessment of aortic regurgitation.

PURPOSE: The purpose of this study was to evaluate the performance of four-dimensional (4D) flow cardiac MRI in quantifying aortic flow in patients with bicuspid aortic valve (BAV). MATERIALS AND METHODS: Patients with BAV who underwent transthoracic echocardiography (TTE) and 4D flow cardiac MRI were prospectively included. Aortic flow was quantified using two-dimensional phase contrast velocimetry at the sinotubular junction and in the ascending aorta and using 4D flow in the regurgitant jet, in the left ventricular outflow tract, at the aortic annulus, the sinotubular junction, and the ascending aorta, with or without anatomical tracking. Flow quantification was compared with ventricular volumes, pulmonary flow using Pearson correlation test, bias and limits of agreement (LOA) using Bland Altman method, and with multiparametric transthoracic echocardiography quantification using weighted kappa test. RESULTS: Eighty-eight patients (63 men, 25 women) with a mean age of 50.5 ± 14.8 (standard deviation) years (age range: 20.8-78.3) were included. Changes in flow with or without tracking were modest (< 5 mL). The best correlation was obtained at the aortic annulus for forward volume (r = 0.84; LOA [-28.4; 25.3] mL) and at the regurgitant jet and sinotubular junction for regurgitant volume (r = 0.68; LOA [-27.8; 33.8] and r = 0.69; LOA [-28.6; 24.2] mL). A combined approach for regurgitant fraction and net volume calculations using forward volume measured at ANN and regurgitant volume at sinotubular junction performed better than each level taken separately (r = 0.90; LOA [-20.7; 10.0] mL and r = 0.48, LOA [-33.8; 33.4] %). The agreement between transthoracic echocardiography and 4D flow cardiac MRI for aortic regurgitation grading was poor (kappa, 0.13 to 0.42). CONCLUSION: In patients with BAV, aortic flow quantification by 4D flow cardiac MRI is the most accurate at the annulus for the forward volume, and at the sinotubular junction or directly in the jet for the regurgitant volume.

Severe Mitral Valve Regurgitation in Infective Endocarditis: A Case Report.

We present a case report of a patient with infective endocarditis. He came to the emergency room with respiratory failure due to severe pneumonia and pulmonary edema. On 2D transesophageal echocardiography, vegetations were seen in both mitral and aortic valves, with mitral valve perforation and severe regurgitation. His clinical presentation and severity of the disease made him suitable for urgent valve repair. He was submitted to mitral valvuloplasty with closure of the valve perforation and insertion of a bioprosthetic aortic valve. Despite significant clinical improvement, a post-surgical complication was noted with new-onset lung injury after cardiopulmonary bypass. This is an interesting case of a patient with suspected retrograde valve involvement, affecting the aortic valve, the mitral-aortic intervalvular fibrosa, and the mitral valve, ending with mitral valve abscess with leaflet perforation and valvular regurgitation.