Patients with a Bicuspid Aortic Valve (BAV) Diagnosed with ECG-Gated Cardiac Multislice Computed Tomography-Analysis of the Reasons for Referral, Classification of Morphological Phenotypes, Co-Occurring Cardiovascular Abnormalities, and Coronary Artery Stenosis.

Background/Objectives: The aim of this study was to analyze a group of patients with a bicuspid aortic valve (BAV) examined with ECG-gated cardiac CT (ECG-CT), focusing on the assessment of the clinical reasons for cardiac CT, cardiovascular abnormalities coexisting with their BAV, and coronary artery stenosis. Methods: A detailed statistical analysis was conducted on 700 patients with a BAV from a group of 15,670 patients examined with ECG-CT. Results: The incidence of a BAV in ECG-CT was 4.6%. The most common reason for examination was suspicion of coronary heart disease-31.1%. Cardiovascular defects most frequently associated with a BAV were a VSD (4.3%) and coarctation of the aorta (3.6%), while among coronary anomalies, they were high-take-off coronary arteries (6.4%) and paracommissural orifice of coronary arteries (4.4%). The analysis of the coronary artery calcium index showed significantly lower values for type 2 BAV compared to other valve types (p < 0.001), with the lowest average age in this group of patients. Moreover, the presence of a raphe between the coronary and non-coronary cusps was associated with a higher rate of significant coronary stenosis compared to other types of BAVs (p < 0.001). Conclusions: The most common reason for referral for cardiac ECG-CT in the group ≤ 40-year-olds with a BAV was the suspicion of congenital cardiovascular defects, while in the group of over 40-year-olds, it was the suspicion of coronary artery disease. The incidence of cardiovascular abnormalities co-occurring with BAV and diagnosed with ECG-CT differs among specific patient subgroups. The presence of a raphe between the coronary and non-coronary cusps appears to be a potential risk factor for significant coronary stenosis in patients with BAVs.

Aortic Regurgitation in Bicuspid Aortic Valve: The Role of Multimodality Imaging.

The evaluation of aortic regurgitation (AR) in bicuspid valve (BAV) is still a challenge because of the eccentricity of the jet, which may under/overestimate the regurgitation. The commonly used echocardiography parameters (such as vena contracta, pressure half-time, etc.) may not be useful in this kind of patient. A multimodality approach combining echocardiography, cardiac MRI, cardiac CT, and advanced technologies applied to non-invasive cardiac imaging (e.g., 4D flow and strain imaging) may be useful to better quantify regurgitation and to select patients suitable for valve replacement. This review provides an overview of the most recent insights about cardiovascular imaging tools and their utility in BAV evaluation, focusing on chronic regurgitation. We describe the role of multimodality imaging in both diagnosis and risk assessment of this disease, pointing out the advantages and disadvantages of the imaging techniques, aiming to provide a guide to clinicians and cardiovascular imaging specialists in choosing the best imaging tools to use.

Pro-angiogenic Cytokine Features for Left Ventricular Remodeling in Patients with Bicuspid Aortic Valve.

BACKGROUND: Bicuspid aortic valve (BAV) is prone to promote the occurrence of left ventricular remodeling (LVR) which is associated with adverse clinical outcomes. Although the association between angiogenic activity and LVR has been established, pro-angiogenic cytokine features and potential biomarker candidates for LVR in BAV patients remain to be clarified. METHODS: From November 2018 to May 2019, BAV patients diagnosed by transthoracic echocardiography at our institution were included. LVR was diagnosed based on echocardiographic calculations of relative wall thickness (RWT) and left ventricular mass index (LVMI). A multiplex ELISA array was used to measure the plasma levels of 60 angiogenesis-related cytokines. RESULTS: Among 103 BAV patients, 71 were categorized into LVR group and 32 into normal LV geometry group. BAV patients with LVR demonstrated increased LVMI, elevated prevalence of moderate to severe aortic stenosis and aortic regurgitation, and decreased left ventricular ejection fraction (LVEF). Plasma level of Angiopoietin-1 was elevated in BAV patients with or without LVR compared to healthy controls (P = 0.001, P < 0.001, respectively) and was negatively correlated with RWT (r = -0.222, P = 0.027). Plasma level of Angiopoietin-2 was elevated in the LVR group (P = 0.001) compared to normal LV geometry group and was negatively correlated with LVEF (r = -0.330, P = 0.002). CONCLUSION: Decreased angiogenesis plays a crucial role in the occurrence and progression of LVR in BAV patients. Disturbance in the pro- and anti-angiogensis equilibrium in BAV patients with LVR may reflect the aggravation of endothelial injury and dysfunction.

Incidence, risk factors, and long-term outcomes associated with permanent pacemaker implantation after aortic root replacement.

OBJECTIVE: Permanent pacemaker implantation (PPI) after AVR is associated with long-term mortality. However, data regarding PPI after aortic root replacement (ARR) is lacking. Herein we describe the incidence, risk factors, and long-term outcomes of PPI after ARR. METHODS: Consecutive patients undergoing ARR from 2005-2020 were selected after excluding those with endocarditis, Type A dissection, or preoperative PPI. Patients requiring PPI after ARR were identified, along with the indication and timing. Independent factors associated with PPI after ARR were identified and long-term survival was assessed. RESULTS: The incidence of PPI was 3.8% (n=85) among 2240 patients undergoing ARR. PPI was performed a median of 7 days (IQR 5-12) after ARR most commonly for complete heart block (73%). Bicuspid aortic valve (OR 1.89, p=0.02), female gender (OR 1.74, p=0.04), preoperative heart block (OR 2.70, p=0.02), and prior AVR (OR 2.18, p=0.01) were independently associated with PPI while preoperative aortic insufficiency (OR 0.52, p=0.01) and VSRR procedure compared to bio-Bentall (OR 0.40, p=0.01) were protective. Patients requiring PPI after ARR were not at increased risk of operative or long-term mortality compared to patients not requiring PPI (p=0.26), however those undergoing PPI suffered from significantly longer hospital length of stay (13 vs 7 days, p<0.001). CONCLUSIONS: The incidence of PPI after ARR remains low, particularly after VSRR. Preoperative conduction disturbance, prior AVR, and bicuspid AV are all associated with increased risk of PPI. While PPI is associated with longer length of stay, it is not associated with early or late mortality.

Bicuspid Aortic Valve Function and Aortopathy on Presentation and Progression in Children: Does Sex Difference Have Any Implications?

Bicuspid aortic valve (BAV) is the most common congenital heart defect. It can be accompanied by aortic regurgitation or stenosis with aortopathies. Studies in adults showed a sex difference, but there are limited number of reports in the pediatric population. To evaluate the difference in bicuspid aortic valve morphology and functionality between sexes, and the presence and progression of aortopathies, a retrospective chart review study was performed at a tertiary referral care center in the Midwest. In our study, we analyzed a cohort of 476 pediatric patients diagnosed with BAV who presented between January 2007 and February 2018. During the follow-up period spanning 2 to 10 years, male patients (n = 314, 66%) had larger aortic valve annulus (AVA) and sinus of Valsalva (SOV) at the time of initial presentation with more likelihood for progression. In the subgroup analysis, the larger SOV in males was observed in isolated BAV patients without genetic syndromes or cardiac malformations, and there were no significant differences between both sexes in the ascending aorta dimension, valve functionality, valve morphology, and the need for intervention in any of the studied groups. As such, these findings may alter the follow-up focus and frequency for patients with BAV, particularly before adulthood, and warrant further studies.

Treatment strategies and outcomes following acute type A aortic dissection repair in patients with bicuspid and tricuspid aortic valves: A meta-analysis.

Background: There is no consensus regarding the strategies for repairing acute type A aortic dissection (ATAAD) in patients with bicuspid aortic valve (BAV). This meta-analysis aimed to compare the treatment strategies and outcomes of ATAAD repair between patients with BAV and those with tricuspid aortic valve (TAV). Methods: A systematic review of databases were performed from inception through March 2023. The primary outcome of interest was all-cause mortality, with a minimum follow-up of 1 year. The secondary outcomes of interest included ratios of performed procedures and rate of distal aortic reoperation. Data were extracted, and pooled analysis was performed using a random-effects model. Results: Eight observational studies including a total of 3701 patients (BAV, n = 349; TAV, n = 3352) were selected for a meta-analysis. Concerning proximal aortic procedures, BAV patients exhibited a higher incidence of necessary root replacement (odds ratio [OR], 6.53; 95% confidence interval [CI], 3.84 to 11.09; P < .01). Regarding distal aortic procedures, extended arch replacement was performed less frequently in BAV patients (OR, 0.69; 95% CI, 0.49 to 0.99; P = .04), whereas hemiarch procedure rates were comparable in the 2 groups. All-cause mortality was lower in the BAV group (hazard ratio, 0.68; 95% CI, 0.50 to 0.92; P = .01). Distal aortic reoperation rates were comparable in the 2 groups. Conclusions: This study highlights distinct procedural patterns in ATAAD patients with BAV and TAV. Despite differing baseline characteristics, BAV patients exhibited superior survival compared to TAV patients, with comparable distal aortic reoperation rates. These findings may be useful for decision making regarding limited versus extended aortic arch repair.

Left ventricular strain-volume loops in bicuspid aortic valve disease: new insights in cardiomechanics.

Aims: By combining temporal changes in left ventricular (LV) global longitudinal strain (GLS) with LV volume, LV strain-volume loops can assess cardiac function across the cardiac cycle. This study compared LV strain-volume loops between bicuspid aortic valve (BAV) patients and controls, and investigated the loop's prognostic value for clinical events. Methods and results: From a prospective cohort of congenital heart disease patients, BAV patients were selected and compared with healthy volunteers, who were matched for age and sex at group level. GLS analysis from apical views was used to construct strain-volume loops. Associations with clinical events, i.e. a composite of all-cause mortality, heart failure, arrhythmias, and aortic valve replacement, were assessed by Cox regression. A total of 113 BAV patients were included (median age 32 years, 40% female). BAV patients demonstrated lower Sslope (0.21%/mL, [Q1-Q3: 0.17-0.28] vs. 0.27%/mL [0.24-0.34], P < 0.001) and ESslope (0.19%/mL [0.12-0.25] vs. 0.29%/mL [0.21-0.43], P < 0.001) compared with controls, but also greater uncoupling during early (0.48 ± 1.29 vs. 0.05 ± 1.21, P = 0.04) and late diastole (0.66 ± 1.02 vs. -0.07 ± 1.07, P < 0.001). Median follow-up duration was 9.9 [9.3-10.4] years. Peak aortic jet velocity (HR 1.22, P = 0.03), enlarged left atrium (HR 3.16, P = 0.003), E/e' ratio (HR 1.17, P = 0.002), GLS (HR 1.16, P = 0.008), and ESslope (HR 0.66, P = 0.04) were associated with the occurrence of clinical events. Conclusion: Greater uncoupling and lower systolic and diastolic slopes were observed in BAV patients compared with healthy controls, suggesting presence of altered LV cardiomechanics. Moreover, lower ESslope was associated with clinical events, highlighting the strain-volume loop's potential as prognostic marker.

Ascending Aortic Progression After Isolated Aortic Valve Replacement Among Patients with Bicuspid and Tricuspid Aortic Valves.

OBJECTIVES: The aims of the present study were to compare the long-term outcomes for ascending aortic dilatation and adverse aortic events after isolated aortic valve replacement between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve ( TAV). METHODS: This retrospective study included 310 patients who had undergone isolated aortic valve replacement with an ascending aorta diameter ≤ 45 mm between January 2010 and September 2021. The patients were divided into BAV group (n=90) and TAV group (n=220). The differences in the dilation rate of the ascending aorta and long-term outcomes were analyzed. RESULTS: Overall survival was 89 ± 4% in the BAV group vs. 75 ± 6% in the TAV group at 10 years postoperatively (P=0.007), yet this difference disappeared after adjusting exclusively for age (P=0.343). The mean annual growth rate of the ascending aorta was similar between the two groups during follow-up (0.5 ± 0.6 mm/year vs. 0.4 ± 0.5 mm/year; P=0.498). Ten-year freedom from adverse aortic events was 98.1% in the BAV group vs. 95.0% in the TAV group (P=0.636). Multivariable analysis revealed preoperative ascending aorta diameter to be a significant predictor of adverse aortic events (hazard ratio: 1.76; 95% confidence interval: 1.33 to 2.38; P<0.001). CONCLUSION: Our study revealed that the long-term survival and the risks of adverse aortic events between BAV and TAV patients were similar after isolated aortic valve replacement. BAV was not a risk factor of adverse aortic events.

Human Genetics of Semilunar Valve and Aortic Arch Anomalies.

Lesions of the semilunar valve and the aortic arch can occur either in isolation or as part of well-described clinical syndromes. The polygenic cause of calcific aortic valve disease will be discussed including the key role of NOTCH1 mutations. In addition, the complex trait of bicuspid aortic valve disease will be outlined, both in sporadic/familial cases and in the context of associated syndromes, such as Alagille, Williams, and Kabuki syndromes. Aortic arch abnormalities particularly coarctation of the aorta and interrupted aortic arch, including their association with syndromes such as Turner and 22q11 deletion, respectively, are also discussed. Finally, the genetic basis of congenital pulmonary valve stenosis is summarized, with particular note to Ras-/mitogen-activated protein kinase (Ras/MAPK) pathway syndromes and other less common associations, such as Holt-Oram syndrome.

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.

Midterm durability of valve-sparing root replacement in bicuspid and tricuspid aortic valves.

Background: Among patients with bicuspid aortic valves (BAV) who are potential candidates for valve-sparing root replacement (VSRR), the long-term durability of this technique is not well understood. This study aimed to compare the clinical and echocardiographic outcomes of VSRR in those with BAV and tricuspid aortic valve (TAV) morphology. Methods: This was a retrospective analysis of patients who underwent VSRR between 2007 and 2021 at a single center. Kaplan-Meier and log-rank analysis were used to estimate and compare freedom from mortality, progression to >2+ aortic insufficiency (AI), and reoperation between groups (BAV vs TAV). Preoperative and postoperative echocardiographic data were collected and assessed for temporal changes in mixed-effect models. Results: A total of 185 patients (BAV, n = 52, 28.1%; TAV, n = 133, 71.9%) underwent VSRR. At baseline, BAV patients were younger (42.4 ± 11.6 vs 52.3 ± 12.6 years; P < 0.01) and had more severe AI (47.9% vs 27.0%; P = 0.02). Average cardiopulmonary bypass and cross-clamp times were similar. There were no differences in rates of postoperative complications, intensive care unit or hospital days, or 30-day readmission. TAV patients' 1-, 5-, and 8-year survival rates were 99.2% [95% CI 97.8-100], 96.7% [93.5-99.9%], and 92.2% [85.6-99.3%], respectively. Overall, there were no differences between groups regarding freedom from mortality (P = 0.18), reoperation (P = 0.51), or recurrent >2+ AI (P = 0.97). . Conclusions: VSRR can be safely performed on patients with BAV and TAV morphology, yielding similar midterm freedom from mortality, recurrent >2+ AI, and reoperation. This technique should be considered in carefully selected patients with aortic root pathology and BAV anatomy when performed at experienced centers.

Molecular Pathways and Animal Models of Semilunar Valve and Aortic Arch Anomalies.

The great arteries of the vertebrate carry blood from the heart to the systemic circulation and are derived from the pharyngeal arch arteries. In higher vertebrates, the pharyngeal arch arteries are a symmetrical series of blood vessels that rapidly remodel during development to become the asymmetric aortic arch arteries carrying oxygenated blood from the left ventricle via the outflow tract. At the base of the aorta, as well as the pulmonary trunk, are the semilunar valves. These valves each have three leaflets and prevent the backflow of blood into the heart. During development, the process of aortic arch and valve formation may go wrong, resulting in cardiovascular defects, and these may, at least in part, be caused by genetic mutations. In this chapter, we will review models harboring genetic mutations that result in cardiovascular defects affecting the great arteries and the semilunar valves.

Effect of graft sizing in valve-sparing aortic root replacement for bicuspid aortic valve: The Goldilocks ratio.

Objective: To investigate the effect of graft sizing on valve performance in valve-sparing aortic root replacement for bicuspid aortic valve. Methods: In addition to a diseased control model, 3 representative groups-free-edge length to aortic/graft diameter (FELAD) ratio <1.3, 1.5 to 1.64, and >1.7-were replicated in explanted porcine aortic roots (n = 3) using straight grafts sized respective to the native free-edge length. They were run on a validated ex vivo univentricular system under physiological parameters for 20 cycles. All groups were tested within the same aortic root to minimize inter-root differences. Outcomes included transvalvular gradient, regurgitation fraction, and orifice area. Linear mixed effects model and pairwise comparisons were employed to compare outcomes across groups. Results: The diseased control had mean transvalvular gradient 10.9 ± 6.30 mm Hg, regurgitation fraction 32.5 ± 4.91%, and orifice area 1.52 ± 0.12 cm2. In ex vivo analysis, all repair groups had improved regurgitation compared with control (P < .001). FELAD <1.3 had the greatest amount of regurgitation among the repair groups (P < .001) and 1.5-1.64 the least (P < .001). FELAD <1.3 and >1.7 exhibited greater mean gradient compared with both control and 1.5 to 1.64 (P < .001). Among the repair groups, 1.5 to 1.64 had the largest orifice area, and >1.7 the smallest (P < .001). Conclusions: For a symmetric bicuspid aortic valve, performance after valve-sparing aortic root replacement shows a bimodal distribution across graft size. As the FELAD ratio departs from 1.5 to 1.64 in either direction, significant increases in transvalvular gradient are observed. FELAD <1.3 may also result in suboptimal improvement of baseline regurgitation.

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.

An Unusual Case of Bicuspid Aortic Valve With Prolapse Masquerading as Cusp Perforation.

We present a unique clinical scenario of a 58-year-old male with a past medical history of hypertension who initially presented with chest pain and was ruled in for non-ST elevation myocardial infarction (NSTEMI) but rapidly developed respiratory failure secondary to aortic insufficiency complicated by cardiogenic shock (CS), attributed to aortic valve prolapse. Intriguingly, the patient had a normal ECG on presentation, underscoring the dynamic nature of valvular pathology. The development of CS highlights the importance of early recognition, prompt diagnosis, and interdisciplinary management in such complex cases.

Double Negative Is Positive: Anomalous Aortic Origin of the Left Coronary Artery Saved by a Bicuspid Aortic Valve.

Atypical aortic origin of coronary artery (AAOCA) is a rare heart condition that has been identified in only a few autopsy cases and in some patients who have undergone angiographic evaluation. AAOCA is known to be closely linked with aortic valve malformations, with the most common type being the bicuspid aortic valve (BAV). A 77-year-old male with a medical history of hypertension and diabetes presented with dyspnea and orthopnea for three days. During the eventual cardiac catheterization, it was noted that the left coronary artery had an anomalous origin from the right side, coursing between the aorta and pulmonary artery. Contrast-enhanced computerized tomography (CECT) also showed a type 2 BAV and a left main coronary artery arising lower at the level of the pulmonary trunk. The dyspnea in this patient was attributed to diastolic dysfunction, and surgical correction of the coronaries was not done. The patient was managed on an outpatient basis for heart failure. In this case, the patient had an anomalous origin of the left coronary artery and type 2 BAV, which posed significant cardiovascular complications. It is unclear if the presence of the concomitant type 2 BAV led to the origin of the anomalous left coronary artery being at a lower level through its effect on the developmental mechanics. This lower origin may have resulted in lower compressive forces on the coronary artery as the inter-arterial pressures would be lower closer to the heart and farther from the lungs. Our case report aims to highlight this complex presentation where the BAV likely provides a benefit in AAOCA cases.

Resumen: Consenso internacional para la nomenclatura y clasificación de la válvula aórtica bicúspide congénita y su aortopatía, con fines clínicos, quirúrgicos, intervencionistas y de investigación / Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes

resumen está disponible en el texto completo

Abstract This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Severe Regurgitant Bicuspid Aortic Valve in a Patient with Overlapping Left Ventricular Noncompaction and Asymmetrical Septal Hypertrophy.

Overlapping of left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy in the same patient is rare and is associated with a more severe clinical course and unfavorable prognosis. The present report describes the case of a severely regurgitant bicuspid aortic valve in a 68-year-old man with overlapping LVNC and asymmetrical septal hypertrophy. Aortic valve replacement controlled the left ventricular dilatation that occurred secondary to the volume overload induced by the valvular disease. However, even 3 years postoperatively, severe systolic dysfunction persisted due to the preexisting myocardial disease, requiring close and lifelong follow-up with special attention to life-threatening arrhythmias and thromboembolism.

Sex differences in transcatheter aortic valve replacement outcomes among patients with bicuspid aortic stenosis.

BACKGROUND: Despite comprising almost half of all patients undergoing valvular repair, data on transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic stenosis (BAS) are limited. OBJECTIVE: We aimed to evaluate whether there are any sex differences in trends and outcomes of TAVR in this population. METHODS: We utilized the National Inpatient Sample from 2012 to 2020 to identify admissions with BAS who underwent TAVR and analyzed trends and outcomes. Our primary outcome was in-hospital mortality and secondary outcomes were in-hospital complications. We used two models to adjust for demographics (A) and interventions (B). RESULTS: Between 2012 to 2020, there were 76,540 hospitalizations for BAS patients who underwent AVR, among which 6,010 (7.9 %) underwent TAVR. There was an overall increasing trend in number of TAVR cases with a decreasing trend in mortality (2013: 8.7 %, 2020: 1.3 %). TAVR was performed more in males (61.1% vs 38.9 %). Despite the worse baseline characteristics in males, in-hospital mortality (2.4% vs. 1.5 %; OR: 1.584; 95 % CI: 0.621-4.038; p = 0.335) and secondary outcomes were similar across both sexes, even after adjusting for demographics and interventions. CONCLUSION: TAVR in BAS has grown rapidly in the last decade. Males comprised the majority and had more comorbidities, but mortality and complications were similar in both sexes. Despite the increasing number of cases, a decreasing trend in mortality was observed for both sexes ultimately approaching that of SAVR, suggesting that TAVR may be a safe alternative among eligible males and females with bicuspid AS.

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.