Abstract
Bicuspid and unicuspid aortic valves represent the most common congenital aortic valve malformations and pose unique challenges in clinical management across the lifespan. These anomalies are associated with progressive valvular dysfunction and aortopathy, often necessitating early intervention. Multiple publications have described life-long management of aortic stenosis (AS), affecting tricuspid valve. This review outlines the embryologic basis, natural history, and clinical spectrum of uni- and bicuspid aortic valve, highlighting diagnostic strategies, surveillance protocols, and surgical– transcatheter interventions. Emphasis is placed on longitudinal care, including transition from pediatric to adult congenital cardiology, multimodality imaging, and timing of surgical or transcatheter interventions. In conclusion, the article aims to provide a framework for evidence-informed, individualized management of these complex valvulo-aortic disorders.
Congenital anomalies of the aortic valve, particularly bicuspid aortic valve (BAV) and the rarer unicuspid aortic valve (UAV), represent a spectrum of developmental abnormalities with significant lifelong implications. BAV is the most common congenital cardiac malformation (often as a part of some genetic syndromes), affecting approximately 0.51% to 1.5% of the population based upon the screening tool used, while UAV is much less prevalent, estimated at ∼0.02%. Both conditions arise from aberrant valvulogenesis during embryonic development, resulting in abnormal valvular architecture that predisposes patients to premature degeneration, progressive stenosis or regurgitation, and ascending aortopathy.
Congenital aortic valve malformations demand a lifelong surveillance strategy that accounts for the dynamic nature of disease progression. While BAV may remain asymptomatic for decades, many patients eventually develop clinically significant valvular dysfunction or thoracic aortic dilatation. BAV may also be associated with aortic coarctation, intracranial aneurysms, and, at times, a parachute mitral valve—features within the spectrum of Shone complex. UAV is often associated with earlier and more severe manifestations, sometimes requiring intervention in childhood or adolescence.
Early recognition, precise anatomical characterization, and longitudinal follow-up are essential to mitigate the risks of sudden cardiac events, aortic dissection, heart failure, or even death. Multimodality imaging, including echocardiography, cardiac computer tomography (CT), and magnetic resonance imaging (MRI) plays a central role in diagnosis and risk stratification. Furthermore, as patients transition from pediatric to adult congenital cardiology services, care coordination becomes critical as they warrant a lifelong follow up.
This review synthesizes current knowledge on the developmental origins, pathophysiology, imaging modalities, and management strategies for UAV and BAV. Particular attention is given to decision-making around timing of surgical or transcatheter interventions, and considerations for family screening and genetic counseling. We aim to provide a structured framework for individualized, lifelong care of patients with these congenital valve disorders.
Embryological Development of the Aortic Valve
The aortic valve develops during early embryogenesis from endocardial cushions in the outflow tract. Semilunar valve development is a tightly regulated process involving endothelial-to-mesenchymal transition (EndMT), cellular migration, and remodeling of endocardial cushions that remodel into valve leaflets. By about 5 to 8 weeks of gestation, the cushions elongate and sculpt into three distinct semilunar cusps under tightly regulated cellular pathways. Normal development involves contributions from neural crest cells and second heart field cells to form a trileaflet valve in concert with the ascending aorta. Various signaling pathways, such as SDF1α/CXCR4 axis, Notch1, TGF-β, and Wnt/β-catenin are critical in orchestrating valve cell lineage specification and extracellular matrix remodeling. Disruption of these pathways results in aberrant EndMT, valve thickening, and myxomatous degeneration, contributing to congenital malformations such as bicuspid or unicuspid aortic valves. Moreover, abnormal fusion of the outflow cushions during embryogenesis is believed to produce a BAV or even a UAV instead of the normal three cusps . In-depth description of aortic valve development has been described in the literature. ,
Genetic Etiologies of Bicuspid/Unicuspid Aortic Valve
BAV is often familial and inherited in an autosomal dominant manner with incomplete penetrance and variable expressivity. This suggests a complex genetic architecture involving multiple interacting loci and modifier genes. Approximately 9% to 15% of first-degree relatives of a BAV patient also have BAV, far above the ∼1% population prevalence. , NOTCH1 was the first single-gene defect identified; heterozygous loss-of-function mutations in this gene can cause bicuspid aortic valve and early-onset calcific aortic stenosis. NOTCH1 haploinsufficiency is associated with BAV and ascending aneurysm. However, NOTCH1 mutations account for only a small fraction of sporadic BAV cases (∼4%), indicating genetic heterogeneity. Other genes have been implicated: for example, SMAD6, an inhibitor of BMP/TGF-β signaling has emerged as a contributor to BAV and related left-sided obstructive defects in some families. Although limited to only a few cases, GATA 4, 5 and 6 (transcription factors) and ROBO4 (involved in endothelial signaling) have been reported in a few BAV cases. In syndromic contexts, BAV is over-represented: Turner syndrome (45,X) females have BAV in up to 30% of cases, often alongside coarctation. Loeys–Dietz syndrome, caused by TGF-β pathway mutations, is strongly associated with BAV (∼10% of these patients have a BAV). Other syndromes occasionally featuring BAV include DiGeorge/22q11.2 deletion (conotruncal defects) and Down syndrome, though these are less frequent. Notably, BAV shares genetic links with other left-heart defects. A landmark study by Hinton et al. demonstrated that hypoplastic left heart syndrome (HLHS) and BAV often cosegregate in families and may share susceptibility loci on chromosomes 10q and 6q. Unlike familial or syndromic forms, sporadic BAV mutations usually present as isolated defects without systemic manifestations, yet they can still predispose to aortopathy, premature calcification, or asymmetric cusp fusion. Their sporadic nature highlights the biological heterogeneity of BAV and suggests that even “nonfamilial” cases have underlying molecular mechanisms that may influence prognosis, surveillance strategies, and individualized management. In summary, genetic etiologies of BAV/UAV span rare high-effect mutations, polygenic factors, and syndromic associations.
Bicuspid/Unicuspid Valves in Hypoplastic Left Heart Syndrome
Severe left ventricular outflow obstruction in utero can lead to HLHS. While the most extreme HLHS cases feature an atretic aortic valve, a substantial subset has a patent but malformed valve, often bicuspid or unicuspid, resulting in critical AS. In a familial HLHS genetic study, among patients with an aortic valve that was open rather than atretic, 38% exhibited a bicuspid and 62% a unicuspid aortic valve, identifying these as the predominant morphologic substrates of critical aortic stenosis. In other words, essentially all nonatretic HLHS aortic valves are either BAV or UAV, with UAV being the more common form in that context. Clinically, HLHS encompasses a spectrum of severity. In milder forms characterized by aortic stenosis rather than complete atresia, the presence of a BAV/UAV suggests that the left ventricle maintained some antegrade blood flow during development, though insufficient to support normal ventricular growth and maturation. Pathological series confirm that many HLHS infants have a severely dysplastic aortic valve with small opening rather than a pure membrane. Fetal intervention strategies have targeted this scenario: if a critically stenotic BAV/UAV is detected in midgestation, balloon valvuloplasty can be attempted to promote left ventricular growth and prevent progression to HLHS. Such fetal procedures have shown partial success in rescuing biventricular outcomes in some cases.
Spectrum of Cardiac Associations With BAV/Unicuspid Valves
BAV is not an isolated finding; it often occurs as part of a broader spectrum of left-heart abnormalities. The classic association is with coarctation of the aorta (CoA), approximately 50% to 85% of patients with CoA have a BAV. BAV is also one component of Shone’s complex , a rare constellation of multiple left-heart obstructive lesions. In Shone’s complex, the aortic valve is frequently bicuspid, whereas unicuspid valves are much rarer. A UAV generally causes severe stenosis early in life, so such patients often present in infancy. Even mitral valve anomalies such as a parachute mitral valve and ventricular septal defects are seen at higher rates with BAV.
BAV-Related Aortopathy: Genetic Anomaly or Flow-Mediated Pathology?
One of the hallmark concerns in BAV patients is ascending aortic dilatation or aortopathy. There has been longstanding debate whether this aortopathy is due to an intrinsic genetic defect in the aortic wall or a secondary effect of abnormal hemodynamics from the BAV. Evidence exists for both mechanisms. Pathologically, the aortic walls of BAV patients (even in nondilated segments) show abnormal matrix organization and smooth muscle cell defects consistent with a developmental anomaly. , Intrinsic abnormalities such as elastin fragmentation, fewer smooth muscle cells point to a genetic/developmental basis making the aorta susceptible to dilation. On the other hand, 4D-flow MRI studies demonstrate that BAVs produce eccentric, high-velocity jets that impinge asymmetrically on the ascending aortic wall, raising wall shear stress (WSS) in specific regions. This turbulent flow can “wear out” and weaken the aortic wall over time. Studies mapping WSS have shown regions of elevated shear correlate with aortic enlargement in BAV patients. Modern consensus suggests that both factors play a role. Some patients likely possess an inherent genetic predisposition, accounting for cases of aortic dissection occurring at relatively small diameters. In contrast, others develop aortic dilation predominantly from hemodynamic stress—particularly when valve stenosis or regurgitation generates high-velocity jets that exert excessive shear forces on the aortic wall. In fact, phenotypic heterogeneity is observed: some BAV patients never develop aortopathy, whereas others do early in life. Recent MRI research strongly supports hemodynamics as a modifier: regions of high systolic wall shear from eccentric BAV flow show greater medial degeneration. In practical terms, this means that all BAV patients require imaging surveillance, including those without significant stenosis.
Sievers Classification of BAV–Rationale and Challenges
BAVs exhibit variability in cusp fusion patterns and raphe formation. In 2007, Sievers and Schmidtke proposed a simple classification to categorize BAV morphology from surgical specimens. The rationale was that a standardized nomenclature would aid in communication and possibly correlate with outcomes. The Sievers classification assigns: Type 0 for a “true” BAV with no raphe; Type 1 for BAV with one raphe (two cusps, but one cusp results from fusion of two commissures, creating an identifiable ridge); and Type 2 for valves with two raphes with usually a complex fusion pattern. Further descriptors note which cusps are fused, such as in Type 1, fusion of right-left is most common, versus right-noncoronary, and the valve function (stenosis, regurgitation, or mixed).
Challenges and Limitations
The Sievers scheme, while widely adopted, has notable shortcomings. First, it was devised from surgical observations, not from imaging, and thus can be ambiguous when applied to echocardiography/CT, as most patients are diagnosed using these modalities. Second, it does not capture the full spectrum of BAV phenotypes—for example, a partial fusion (an incomplete raphe) or cusp asymmetry, sometimes called a “forme fruste” BAV, isn’t well-described by Sievers’ numeric types. Third, Sievers lumped the unicuspid aortic valve as “Type 2 BAV” because surgically it appeared as two raphes, giving one opening. We now recognize unicuspid valves are embryologically distinct and behave differently clinically; thus, treating them as a subset of BAV is misleading. Furthermore, the Sievers system ignores the aortic root and annular geometry, which is crucial in BAV disease. Two BAVs of the same type might have very different aortic root phenotypes; Sievers classification wouldn’t distinguish them. This is important for valve-sparing surgery or repair planning, where cusp symmetry and annulus size matter. Also, Sievers classification doesn’t address cusp size symmetry . Some BAVs have one very large cusp and one small cusp (asymmetric BAV), others are more symmetric; this can affect surgical repair feasibility. Due to these issues, an international consensus in 2022 proposed a new nomenclature that is more comprehensive, incorporating valve phenotype, valve function, presence/characteristic of raphe, cusp shape/size, BAV symmetry, and aortopathy phenotype. Jilaihawi et al. propose another BAV classification, and divides valves into three types—tricommissural, bicommissural with raphe, and bicommissural without raphe, to help better understand how implanted valves interact with the native valve structure, based on the number of commissures and whether a raphe is present at the leaflet base. Various BAV classifications are described in Figure 1 .
Bicuspid aortic valve classifications.
Aortic Annulus in Bicuspid Versus Tricuspid Valve
Bicuspid valves not only alter cusp number but also the geometry of the annulus and valve orifice. Generally, BAV patients have an annulus that is more elliptical rather than circular, with a larger difference between minor and major diameters than normal tricuspid aortic valves. Additionally, many BAV patients have larger annular dimensions. In transcatheter valve studies, BAV anatomy has been noted for “frequent large size, elliptical shape, and asymmetric cusps.” In addition, the coronary arteries more often have an eccentric origin in the cusp(s). Surgical series have also described that BAV patients often require larger prostheses on average than tricuspid AS patients. The shape is equally important: an elliptical annulus poses challenges for valve seating and sealing; these challenges are described further down. Most BAV patients develop early calcific aortic stenosis, though a subset develops aortic regurgitation. Notably, the right-noncoronary cusp fusion phenotype tends to experience more severe regurgitation and faster progression of valve insufficiency, especially in pediatric patients.
Various treatment options exist treating stenotic bicuspid aortic valve, whereas management of regurgitant BAV is challenging. Surgically, BAV patients often require intervention on an enlarged aortic root (guidelines advise replacing the root if ≥45 mm during valve surgery). Moreover, valve repair is technically difficult when cusps are asymmetrical; symmetrical BAVs are far easier to repair. Transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) is challenging because the annulus is often large and elliptical and the raphe frequently calcified, increasing the risks of paravalvular leak and, at times, the need for a second valve. Nevertheless, outcomes have improved markedly in recent years, with substantial success treating selected BAV patients using TAVR. By contrast, most patients with isolated, pure aortic regurgitation in the setting of BAV still require surgical repair.
On the other hand, unicuspid aortic valves which typically present in younger patients with severe stenosis have very small, often hypoplastic annuli. By adulthood, many UAV patients have required surgery, but those who reach adulthood show markedly small annular size. This has implications for surgical and transcatheter intervention; surgeons may perform annular reduction procedures if the annulus is very large in a BAV with regurgitation, and TAVR operators must carefully size devices to the elliptical annulus to avoid leak or rupture.
Lifelong Management of Uni- and Bicuspid Aortic Valve Disease and Associated Pathologies
Fetal aortic valve interventions and outcomes
For fetuses diagnosed with critical AS (often due to a BAV or UAV), who are at risk of evolving into HLHS, in utero intervention can be considered. Fetal aortic valvuloplasty is typically performed around 20 to 30 weeks’ gestation: a needle is inserted through the maternal abdomen through uterus into the fetal left ventricle, and a balloon is used to open the stenotic aortic valve. The goal is to promote forward flow and left heart growth. Pioneered by teams in Boston, this procedure has shown that some fetuses can indeed transition from a potential HLHS to a two-ventricle circulation at birth. However, outcomes are mixed and highly dependent on case selection and technical success. Their 20 years of experience reported that technical success was achieved in a majority of attempts, and among those successfully dilated, about 50% of liveborn infants achieved a biventricular circulation, whereas the other half ultimately still required single-ventricle palliation. This roughly coin-flip probability of avoiding HLHS suggests that some left ventricles do not normalize despite relieving aortic valve obstruction. Importantly, such fetal intervention carries significant risks. Their data (2000 to 2020) showed an overall fetal mortality of ∼8% associated with the procedure. Additionally, serious maternal or fetal adverse events (like bradycardia, pericardial effusion, preterm labor) occurred in ∼40% of cases. An international registry reported even higher fetal loss (∼18%) at centers outside the highest-volume programs. Such high risks have to be balanced against the potential benefit of a two-ventricle outcome as opposed to HLHS. Over time, refinements such as better imaging, patient selection criteria including adequate left ventricular size and function to justify intervention, and technique improvements have modestly improved success rates. Those cases that do achieve a two-ventricle circulation stand as proof of principle that early intervention on a BAV/UAV can alter the disease trajectory, essentially “buying time” for the left heart to grow before birth.
Aortic valve interventions in childhood: mechanical valves and their complications
When infants, children, or teenagers require aortic valve replacement, one option is a mechanical prosthetic valve, and an alternative option is the Ross procedure. Mechanical valves are durable, but in young patients they pose significant challenges. First, a child’s annulus will grow, a fixed-size prosthesis can result in patient-prosthesis mismatch as the child grows, often necessitating reoperation to upsize the valve. A study from Boston Children’s (121 patients, median age at AVR 16, median follow up-5 years) found freedom from reoperation was ∼91% at 7 years and ∼78% at 10 years after mechanical aortic valve replacement. Younger age and smaller valve size strongly predict the need for reoperation. Secondly, mechanical valves mandate lifelong anticoagulation and carries a risk of bleeding and thromboembolism. In the Boston series, the annual risk of major thromboembolism was ∼0.66% per patient-year and major bleeding ∼0.83% per year. Over a childhood and adolescence, this accumulates-roughly a 10% to 15% chance of a serious clot or hemorrhage by 20 years on anticoagulation. Thirdly, the surgical implant of a mechanical valve in a small annulus may involve a higher risk of heart block, requiring a permanent pacemaker.
Additionally, mechanical valves are not as benign in children as in adults; children are more active and may experience higher risk of trauma causing bleeding. Over time, these patients may require pacemaker revisions, implantation of new leads, and may develop complications such as device-related infections, lead extractions, and progressive tricuspid regurgitation.
In patients, where maintaining an international normalized ratio >2 is not feasible, the FDA-approved On-X mechanical valve (On-X Life Technologies, Austin, TX) has demonstrated superior hemodynamic performance and enhanced thromboresistance, permitting safe anticoagulation at lower INR levels (1.5 to 2.0). Additionally, evidence from observational studies, propensity-matched analyses, randomized controlled trials, and meta-analyses suggests a survival advantage of mechanical over bioprosthetic aortic valves, particularly in patients under 65 years of age, due to the limited long-term durability of bioprosthetic valves. Thus, while mechanical valves “solve” the immediate problem of a stenotic valve, they introduce a lifelong management burden. This has driven interest in alternatives like the Ross procedure or advanced repairs, despite their own complexities.
The Ross procedure: outcomes and challenges
The Ross procedure, replacing the diseased aortic valve with the patient’s own pulmonary valve as an autograft, and a donor homograft in the pulmonary position offers an attractive solution for children and young adults because the autograft can grow, and no anticoagulation is needed. In the hands of experienced surgeons, the Ross has yielded outstanding long-term results. Dr. David’s 20-year Ross cohort (212 patients, mean age 34) had a survival of 93.6% at 20 years, which was indistinguishable from an age-matched general population. This is remarkable, essentially restoring normal life expectancy in young patients, something mechanical valves have not definitively shown. Furthermore, freedom from any reoperation on either the autograft or homograft was ∼80% at 20 years. The autograft (neoaortic valve) tends to be the Achilles’ heel: some patients developed progressive autograft dilatation and aortic regurgitation over time (freedom from significant AI ∼63% at 20 years). Male sex, aortic insufficiency as the primary mode of native valve failure, and aortic annular diameter ≥15 mm/m 2 are independent risk factors for autograft dysfunction. Nonetheless, the clinical outcomes such as survival and quality of life remain superb for Ross patients who are cared for properly. Other centers with Ross expertise similarly report 90%+ survival at 15 to 20 years and low stroke risk. A propensity-matched study even showed young adults had better long-term survival with Ross than with mechanical AVR, and far fewer thromboembolic complications. ,
However, the Ross procedure is technically demanding, essentially a double-valve surgery with a complex root replacement. It is highly operator dependent. As Dr. Tirone David has argued, the Ross done by an expert can be “as close to a perfect AVR substitute as currently possible, but many surgeons never embark on the learning curve.” The pulmonary autograft must be seated and supported in the aortic root such that it does not dilate; various techniques such as fully free-standing root vs inclusion technique vs reinforcement with Dacron exist, each with pros and cons. Some experts emphasize aligning the pulmonary annulus at or below the aortic annulus level and supporting the pulmonary root’s commissures externally to prevent late expansion. Differences in anatomy especially common in BAV patients who often have annular dilation or asymmetry add to the complexity.
An important challenge is reintervention: when the Ross fails, reoperations can be technically complex, sometimes requiring root replacement and a new pulmonary homograft. Thus, ensuring the Ross is done correctly initially is paramount. Operator experience greatly influences outcomes: a high-volume Ross surgeon can have operative mortality under 1% to 2% and low reoperation rates, whereas low-volume centers have reported higher early failures. Because of this, there’s a push in recent years for regional Ross centers of excellence. The challenges are ensuring widespread expertise and recognizing ideal candidates, such as those without connective tissue disorders and with manageable root size.
Surgical AVR in BAV patients: from Bentall to Cabrol grafts
When adults with BAV undergo conventional surgical aortic valve replacement (SAVR), surgeons must also address any concomitant aortic dilation. Many BAV patients, by the time of surgery, have an enlarged ascending aorta or even aneurysm of the root. The standard approach if the aortic root is aneurysmal is a Bentall procedure, a composite graft replacing the aortic root and valve (mechanical or biological), with reimplantation of the coronary arteries. Apart from this, BAV patients generally undergo SAVR similarly to tricuspid AV patients, or valve-sparing root replacement if only root is enlarged, and the valve is competent.
One specific advanced technique is the Cabrol procedure using Cabrol grafts, which is occasionally used in complex aortic root surgeries. A Cabrol graft is a small Dacron graft used to connect the coronary ostia to the main aortic graft when direct reimplantation of coronaries is difficult. It was originally devised for cases of aortic root replacement in which the coronary arteries could not be directly reattached without tension. In modern practice, the Cabrol technique is reserved for complicated scenarios: reoperations where scar tissue prevents mobilization of the coronaries, or massive roots where the coronary buttons won’t reach the new graft easily. Essentially, the Cabrol entails sewing a side graft from the main aortic graft and then anastomosing that side graft to the coronary ostia, forming a little “bridge” ( Video 1 & 2 ). This can prevent kinking or tension that might otherwise cause coronary insufficiency or pseudoaneurysm at the reimplant site. They are relatively rare (<5% of root replacements in experienced centers), but surgeons keep it in the armamentarium for complex BAV aortopathies, especially in redo operations or unusual anatomy.
Valve-sparing operations: In young BAV patients with aortic root aneurysm but not severely diseased leaflets, a valve-sparing root replacement (David procedure) can be attempted. BAV leaflets can sometimes be repaired (free edge plication, raphe resection) and then the root replaced with Dacron while resuspending the native valve. This is technically demanding, and long-term durability is an active research area. BAV anatomy especially if the cusps are asymmetric or calcified makes such repairs tricky, but in certain cases it avoids a prosthesis. Some centers have reported success in select BAV cases, but this is an evolving field.
Finally, it’s worth mentioning the Ozaki procedure that involves aortic valve reconstruction using glutaraldehyde treated autologous pericardium to create new valve cusps tailored to the patient’s annular dimensions. Originally developed for tricuspid valve disease, it has shown promise in treating BAV, especially in young adults, by restoring more physiological valve geometry and hemodynamics. Compared to mechanical or bioprosthetic valves, it avoids lifelong anticoagulation and may reduce structural valve degeneration. Early data suggest favorable midterm outcomes in BAV patients undergoing Ozaki repair, with low reoperation rates and preserved valve function, though long-term durability remains under investigation. , Life long management of uni-, and bicuspid aortic valve and associated complications are described in the central figure.
Late presentation of BAV and BAV prevalence in early TAVR trials
While BAVs often become dysfunctional by midlife, a subset of BAV individuals remain relatively asymptomatic until old age. In fact, it’s been noted that over 20% of patients with BAV who eventually require valve replacement are older than 80 years. One series found ∼60% of BAV patients needing surgery were <70, but a significant minority (>20%) were octogenarians. These “late presenters” usually have either a less severe fusion pattern or have avoided heavy calcification. Because of this, when transcatheter aortic valve replacement (TAVR) came onto the scene, it became apparent that some 70- and 80-year-olds with severe AS actually had unrecognized BAV. However, in the early pivotal TAVR trials, BAV patients were largely excluded, as trial designers were worried about device behavior in BAV anatomy. For example, in the PARTNER trials did not include bicuspid valves, so none of that data reflected BAV outcomes. Similarly, CoreValve trials excluded significant aortopathy which effectively excluded many BAVs. Registries in the early TAVR era that did treat BAV reported how challenging it was. Specifically, early-generation balloon-expandable and self-expanding valves had more frequent moderate or greater paravalvular leak (PVL), high-degree conduction disorders and need for a second valve when used to treat bicuspid AS. There were also concerns for annular rupture, a catastrophic complication in heavily calcified BAVs ( Video 3 ). As a result, when TAVR was first approved for high (2012) and intermediate (2016) surgical risk patients, it was officially only for tricuspid valves, with BAV being “off-label.”
Over time, however, as TAVR technology and techniques improved including third-generation valves with sealing skirts, improved CT sizing protocols, etc., outcomes in BAV have improved, and many elderly BAV patients are now routinely treated with TAVR. Recent publications indicate that in carefully selected older BAV patients, TAVR outcomes (30-day and 1-year mortality and stroke) can be comparable to tricuspid AS patients. , In contemporary practice, 10% to 20% of patients treated with TAVR in advanced centers may have a bicuspid anatomy. However, the findings in the recent NOTION-2 trial remind us that patient selection and procedural optimization is key when performing TAVR in bicuspid AS patients: those with a unicuspid aortic valve or excessively calcified leaflets in combination with a long, calcified raphe might still fare better with surgery. Furthermore, avoiding severe transcatheter heart valve underexpansion and multiple valve repositioning’s (in case of use of self-expanding valves) should be strived for.
To directly answer the prompt: Why do some BAV not present till late? BAV disease severity varies, some have near-normal function well into old age, whereas others present in the early years of their lives. However, an important question remains: do patients presenting later in life with aortic stenosis and a bicuspid aortic valve represent a distinct phenotype that is more amenable to TAVR, and can younger patients with severe aortic stenosis achieve similarly favorable outcomes with transcatheter intervention? Precise mechanistic aspect explaining the differences has not been well described. As TAVR moved to lower risk and younger patients, the need to treat BAV grew, prompting new studies. For instance, the Evolut Low-Risk Bicuspid Study specifically evaluated TAVR in BAV patients around 70 years old and showed encouraging 3-year outcomes (all-cause mortality and stroke rates ∼10% or less). However, these patients were highly selected. Our understanding of TAVR as a therapeutic option for patients with bicuspid aortic valve, across different age groups and anatomical variants, is expected to evolve and improve over time.
TAVR challenges in bicuspid valves and influence of sievers classification
TAVR in bicuspid anatomy is technically more challenging than in trileaflet valves. The difficulties arise from BAV’s irregular geometry and calcification pattern. Key challenges include: (1) Annular eccentricity: as noted, BAV annulus is oval, which can lead to incomplete sealing of a circular TAVR frame, hence more PVL. (2) Raphe calcification: many BAVs especially Sievers Type 1 with one raphe have a heavy calcified ridge along the fused commissure. This rigid bar of calcium can prevent the TAVR stent from expanding fully ( Figure 2 ) or can protrude and cause paravalvular gaps or even annular rupture, if aggressively dilated ( Video 3 & 4 ). (3) Aortic root dilation: BAV patients often have an enlarged root or ascending aorta, possibly affecting device anchoring and increasing the chance of residual AR. (4) Asymmetric leaflet deployment: BAV’s two cusps can cause the TAVR valve to sit at an angle or with one side more constrained ( Figure 2 ).
Eccentric expansion of a transcatheter aortic valve in a bicuspid anatomy. (A) Constrained valve in cusp-overlap view before postdilatation; After postdilatation the TAVR valve in (B) cusp-overlap view, and (C) three cusp view.
The Sievers classification ties in because different BAV types behave differently in TAVR:
-
1.
Type 0 BAV: This typically has two, relatively symmetric cusps. In TAVR, Type 0 can sometimes achieve a more circular deployment because there isn’t a raphe preventing expansion. Studies have suggested Type 0 BAV might have lower rates of PVL compared to Type 1. However, Type 0 is the least common; ∼10% of bicuspid valves. Its challenges are still an oval annulus and possibly very large annular size. But the absence of a raphe means less calcific distortion of the frame, often resulting in a better seal.
-
2.
Type 1 BAV: This is the most common (about 70% to 80% of BAV). Here, the presence of a raphe, especially if heavily calcified is a focal point of difficulty. The TAVR stent may expand in a “D-shape” with the raphe as the flat side. This can result in a higher risk of PVL and THV under-expansion and, consequently, leaflet thickening/thrombosis. Type 1 BAV also often has one cusp larger than the other, creating asymmetry. Some data suggest Type 1 BAV after TAVR has higher residual gradients but maybe slightly less symmetrical expansion than Type 0. Post dilating valves in such anatomy may contributed to conduction issues, or rarely annular rupture.
-
3.
Type 2 BAV: This is exceedingly rare and often essentially behaves as a unicuspid valve. Such valves typically are extremely stenotic and usually present at a younger age and conventionally treated surgically. As reported in the NOTION-2 trial, these patients have a high risk of immediate or late aortic annulus rupture. These patients should preferably be treated by surgery.
Other anatomic considerations: Raphe fusion pattern may influence outcomes. Several studies suggest right-noncoronary (R-NC) fusion BAVs have more elliptical annuli and a greater tendency toward root dilation than right-left (R-L) fusion. Practical TAVR implications: Accurate sizing is critical. Use CT-based measurements of annular area and minimum/maximum diameters; plan slight oversizing to achieve seal but avoid excessive oversizing that risks annular injury/rupture. Many BAV cases benefit from balloon predilation to fracture calcium and assess compliance, with selective postdilation to minimize paravalvular leak. New-generation valves (Sapien 3, Evolut R/PRO) have markedly improved results, with moderate-or-worse PVL now ∼3% to 5% in BAV cohorts—approaching rates seen in tricuspid AS. Table 1 presents selected studies evaluating TAVR outcomes for bicuspid and tricuspid aortic stenosis.
Table 1
TAVR outcomes in bicuspid versus tricuspid aortic stenosis
| Study | TAVI procedural success & complications (BAV vs TAV) | Long-term outcomes (BAV vs TAV) |
|---|---|---|
| Yoon et al. (JACC 2017) International Bicuspid AS TAVR Registry |
• BAV:
• Conversion to surgery: 2.0% versus 0.2% ( p = 0.006) • Device success: 85.3% versus 91.4% ( p = 0.002) • SEV: Frequent moderate to severe PVL (19.4% vs 10.5%; p = 0.02) • BEV: Frequent aortic root injury (4.5% vs 0.0%; p = 0.015). |
• 2-year all-cause mortality: 17.2% versus 19.4% ( p = 0.28). |
| Makkar et al. (JAMA 2019) -STS/ACC TVT Registry analysis |
• BAV:
• 30-day stroke: 2.5% versus 1.6% (significantly higher in BAV). • Emergent conversion to surgery: 0.9% versus 0.4% • Moderate-or-severe PVL at 30 days: 2.0% versus 2.4% ( p = ns). |
• 1-year all-cause mortality: 10.5% versus 12.0% (
p
= ns).
• 1-year, overall outcomes (including mortality and stroke) were similar for BAV and TAV patients. |
| Halim et al., (Circ. 2020) STS/ACC TVT Registry analysis |
• BAV:
• Younger, and low STS score. • Current generation THV-BAV vs TAV: • Lower device success (BAV- 96.3% vs 97.4% in tricuspid, p = 0.07), • Moderate to severe PVL (2.7% vs 2.1%; p < 0.001). • BAV: Current versus previous generation of THV • Device success (96.3 vs 93.5; p = 0.001) • Low incidence of moderate to severe PVL (2.7% vs 14.0%; p < 0.001). • 30-day outcomes (mortality, stroke and major bleeding) were similar. |
• 1-year outcomes (mortality, stroke and major bleeding) were similar.
• No differences in valve hemodynamics or need for reintervention. • BAV versus TAV at 1-year • No difference in stroke (HR 1.14 [95% CI, 0.94 to 1.39]) • Lower risk of death (HR 0.88 [95% CI, 0.78 to 0.99]) |
| Makkar et al., (JAMA 2021) STS/ACC TVT Registry analysis |
• TAVR using BEV treating BAV versus TAV (low STS cohort)
• Death at 30 days (0.9% vs 0.8%; HR 1.18 [95% CI, 0.68 to 2.03]; p = 0.55) • Stroke at 30 days (1.4% vs 1.2%; HR, 1.14 [95% CI, 0.73 to 1.78]; p = 0.55) • No major differences in acute device success, hemodynamics (mean AVG 13.2 vs 13.5 mmHg), and moderate to severe PVL (3.4% vs 2.1%. |
• Death at 1-year (4.6% vs 6.6%; HR, 0.75 [95% CI, 0.55 to 1.02]; p = 0.06) (? BAV patients being younger at the time of intervention). |
| Al-Asad et al., (Am J Cardiol 2023) Meta-analysis and systemic review |
• Meta-analysis of the 30 studies comparing TAVR in BAV versus TAV
• At 30-days (all patients-matched cohort) • Higher rate of stroke (3.3% vs 2.4%; OR 1.24, 95% CI 1.08 to 1.43, p < 0.05) • Other 30-day outcomes (e.g. pacemaker, moderate/severe PVL, life-threatening bleeding) did not significantly differ between groups. • Subgroup analysis of low-surgical risk patients • Similar rate of stroke at 30-days (OR 1.24, 95% CI 0.83 to 1.88, p = 0.30) |
• 1-year all-cause mortality lower for BAV (OR0.86, CI 0.75 to 0.98;
p
= 0.02).
• 1-year mortality– lower rate in BEV versus SEV (OR 0.79, 95% CI 0.66 to 0.94, p < 0.05). |
| Jørgensen et al. (NOTION-2 Trial, EHJ 2024) -Low-risk patients ≤75 yrs |
• BAV:
• Moderate-or-greater paravalvular leak frequent in BAV: 9.1% versus 3.1%. • New permanent pacemaker: 14.6% versus 15.2% ( p = ns). |
• 1-year death or disabling stroke: 6.1% versus 2.2%.
• 1-year composite (death, stroke or rehospitalization): 14.3% versus 8.7% • BAV patients treated with TAVR showed higher rates of non-disabling stroke and moderate PVL, warranting caution. |
| Gitto et al., (AD-HOC registry, Int J Cardiol 2025) |
• TAVR-Sievers-1 BAV (women vs men)
• Women: • Smaller aortic dimensions & lower calcific burden of raphe. • Low VARC-3 technical success (93.7% vs 95.8%; adj OR 0.37, 95% CI 0.17 to 0.81) • Lower device success (83.5% vs 86.6%; adj OR 0.61, 95% CI 0.38 to 0.98) • Frequent major peri‑procedural bleeding. |
• Long-term (3-year MAE): 19.7% (women) versus 25.6% (men); no significant sex difference (adj HR 0.75, 95% CI 0.47 to 1.20).
• Prognostic determinants differed (men): diabetes/COPD/severe calcification; (women): CKD; better hemodynamic performance & higher baseline gradient appeared protective. |
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