Aortic Stenosis

Definition

Aortic stenosis (AS) is progressive obstruction of LV outflow due to calcification/fibrosis of aortic valve cusps or rheumatic involvement, leading to increased LV afterload and, if untreated, LV dysfunction and death. It is the most common primary valve lesion referred for intervention in Europe and North America.

Key Concepts

Epidemiology

• Prevalence rising with ageing population; degenerative calcific aetiology dominates in high-income countries
• Bicuspid AV (BAV): dominant morphology in younger patients requiring AV replacement; associated with aortic dilatation in >50%
• Rheumatic AS common in low/middle-income countries; usually presents combined with rheumatic MV disease sources/vhd-esc-2025 very high

Echocardiographic Grading

• High-gradient (severe): mean PG ≥40 mmHg, Vmax ≥4.0 m/s, AVA ≤1 cm² (AVAi ≤0.6 cm²/m²) — severe regardless of flow/EF
• Low-flow, low-gradient with reduced LVEF (<50%): AVA ≤1 cm², SVi ≤35 mL/m², mean PG <40 mmHg — distinguish true severe from pseudo-severe using DSE (flow reserve = ≥20% increase in stroke volume) or CCT calcium scoring
• Low-flow, low-gradient with preserved LVEF (≥50%): AVA ≤1 cm², SVi ≤35 mL/m², mean PG <40 mmHg — often elderly women; multimodality workup required
• Normal-flow, low-gradient with preserved EF: usually moderate AS; prognosis similar to moderate AS unless multimodality confirms severe
• CCT AV calcium score: >2000 AU (men) / >1200 AU (women) = severe AS with ~85% sensitivity and specificity; <1600 AU (men) / <800 AU (women) makes severe AS unlikely sources/vhd-esc-2025 very high

Additional Diagnostic Parameters

• GLS <−15% identifies high-risk asymptomatic patients
• Natriuretic peptides help arbitrate symptom sources and identify high-risk asymptomatic patients (>3× age/sex normal = adverse marker)
• Exercise testing: unmask symptoms and haemodynamic intolerance (fall in BP >20 mmHg = adverse)
• Transthyretin cardiac amyloidosis co-exists in elderly AS patients — screen with immunofixation + bone scintigraphy if suspected; valve intervention still beneficial despite co-existing ATTR sources/vhd-esc-2025 very high

Medical Therapy

• No proven medical therapy delays AS progression; statins ineffective despite pre-clinical promise
• Treat concomitant hypertension (renin-angiotensin blockers preferred, careful titration to avoid hypotension)
• HF and reduced LVEF: initiate GDMT before and up-titrate after valve intervention sources/vhd-esc-2025 very high

CAVD Molecular Mechanisms and Emerging Therapies

• CAVD pathogenesis: shear/mechanical stress → VEC disruption → lipid infiltration, inflammation, oxidative stress → osteogenic transformation of VICs → ECM disruption and extracellular vesicle-mediated calcification sources/vhd-mechanism-aha-2024 (very high)
• Calcification initiated in the fibrosa, typically the noncoronary cusp first
• Disease initiation vs progression are distinct processes: Lp(a) and LDL-C have independent causal roles in CAVD initiation (Mendelian randomization); however, Lp(a) is NOT associated with progression of established valve calcification — explains statin trial failures sources/vhd-mechanism-aha-2024 (very high)
• Statin paradox: strong genetic evidence implicates lipids in CAVD onset, yet statins (SALTIRE trial) showed no benefit on AS progression — consistent with initiation/progression mechanistic divergence sources/vhd-mechanism-aha-2024 (very high)
• CHIP (clonal hematopoiesis of indeterminate potential): somatic variants in hematopoietic stem cells; present in CAVD and portend worse prognosis after AVR; augments NLRP3 inflammasome-mediated programs sources/vhd-mechanism-aha-2024 (very high)
• See concepts/CAVD-Mechanisms for full molecular pathway detail
• Ongoing trials targeting AS progression: pelacarsen (Lp(a) lowering, NCT05646381); colchicine (CHIANTI, COPAS); PCSK9 inhibitor (NCT04968509); evogliptin DPP4 inhibitor (EVOID-AS); ARBs (ARBAS); pioglitazone sources/vhd-mechanism-aha-2024 (very high)

Indications for Intervention — Symptomatic Severe AS

• Class I: All eligible symptomatic patients with high-gradient AS (life expectancy >1 year)
• Low-flow, low-gradient + reduced LVEF: Class I B if severe AS confirmed (DSE or CCT); pseudo-severe AS → GDMT only
• Low-flow, low-gradient + preserved LVEF: Class IIa — intervention after confirming severe AS
• Normal-flow, low-gradient + preserved EF: usually moderate AS; regular surveillance unless multimodality confirms severe sources/vhd-esc-2025 very high

Indications for Intervention — Asymptomatic Severe AS

• Class I: LVEF <50% without other cause
• Class IIa (new 2025): Early intervention as alternative to watchful waiting in patients with high-gradient AS, LVEF ≥50%, confirmed asymptomatic (normal exercise test if feasible), and low procedural risk — supported by EARLY TAVR, RECOVERY, AVATAR, EVoLVeD trials and meta-analysis
• Additional adverse features favouring early intervention: very high Vmax (≥5 m/s), severe calcification + Vmax progression ≥0.3 m/s/year, markedly elevated BNP/NT-proBNP (>3× age/sex-corrected normal on repeated measurements), LVEF <55%
• Moderate AS: intervention only if undergoing CABG, ascending aorta, or other valve surgery; evidence emerging for moderate AS + HFrEF but insufficient for routine intervention sources/vhd-esc-2025 very high

TAVI vs SAVR — Mode of Intervention

• Heart Team decision integrating: age, life expectancy, procedural risk (STS/EuroSCORE), anatomical suitability, patient preference, and lifetime management
• TAVI non-inferior to SAVR in low-risk, intermediate-risk, and high-risk symptomatic patients at mid-term follow-up (PARTNER 3, Evolut Low Risk, DEDICATE trials)
• BHV preferred for most patients ≥65 years (aortic) or ≥70 years (mitral)
• MHV preferred for patients <60 years (aortic) or <65 years (mitral) with long life expectancy and no contraindication to OAC
• Anatomical factors favouring SAVR: low coronary ostia, narrow aortic root, commissural misalignment, BAV morphology, severe LVOT calcification
• TAVI for BAV stenosis at high surgical risk (new Class IIb B 2025): if anatomy suitable per Heart Team sources/vhd-esc-2025 very high
• See also: concepts/TAVI

Concomitant AV Replacement During Other Surgery

• Class IIa: SAVR in patients with moderate AS undergoing surgery for another valve
• Class IIb: SAVR in patients with moderate AS undergoing CABG or ascending aorta surgery sources/vhd-esc-2025 very high

ACC/AHA 2020 — TAVI vs SAVR Age-Based Framework

• Class I A: Age <65 years or life expectancy >20 years → SAVR recommended (TAVI durability data extend only to ~5 years)
• Class I A: Age 65–80 years + no contraindication to transfemoral TAVI → either SAVR or transfemoral TAVI after shared decision-making
• Class I A: Age >80 years or life expectancy <10 years + no contraindication → transfemoral TAVI recommended in preference to SAVR
• Class I A: High or prohibitive surgical risk, predicted post-TAVI survival >12 months → TAVI regardless of age
• These age-specific thresholds contrast with the ESC 2025 approach which uses a Heart Team decision rather than fixed age thresholds sources/VHD-AHA-2020 very high

Invasive Hemodynamic Assessment of AS

• Catheterization is reserved for cases where Doppler echo is inconclusive or discordant with clinical findings; if mean gradient ≥40 mmHg and clinical findings are consistent, no further invasive hemodynamic data are needed (except when CO >6.5 L/min) sources/hemodynamics-circ-2012 high
• Optimal technique: simultaneous LV and central aortic pressure via side-hole catheters; mean gradient (integrated systolic ejection period) preferred — peak-to-peak gradient is non-physiological (peak LV and peak Ao pressure occur at different times) sources/hemodynamics-circ-2012 high
• Never use femoral artery pressure as a surrogate for central Ao: peripheral amplification and vascular stenosis cause false under/over-estimation; there is also a temporal delay affecting mean gradient calculation sources/hemodynamics-circ-2012 high
• Carabello sign: the catheter crossing critical AS (AVA ≤0.7 cm²) with a 7–8F catheter causes additional obstruction — recognise by noting a further pressure drop during catheter pullback; do not attribute solely to valve pathology sources/hemodynamics-circ-2012 high
• Gorlin formula (1951): A = F / (Cc × Cv × √2gh); empirical constant used only for mitral valve; coefficients assumed = 1 for aortic valve (a theoretical impossibility); valve areas have clear limitations — must be interpreted alongside gradient, pressure contours, and ventricular contractile state sources/hemodynamics-circ-2012 high
• Hakki equation (bedside check): valve area = cardiac output / √mean gradient; use to verify computer-generated Gorlin calculation sources/hemodynamics-circ-2012 high
• Pressure contour analysis: Fixed valvular obstruction → parvus et tardus upstroke from time of AV opening; dynamic LVOTO (HCM) → spike-and-dome contour with late-peaking LV pressure sources/hemodynamics-circ-2012 high
• Braunwald-Brockenborough sign: Post-PVC beat: valvular AS → increased pulse pressure; HCM → decreased pulse pressure — distinguishes fixed from dynamic obstruction sources/hemodynamics-circ-2012 high
• Dobutamine challenge for low-flow/low-gradient AS (reduced LVEF): True severe AS: gradient increases, valve area remains small (≤0.7 cm²); Pseudo-AS: gradient unchanged, valve area normalises (≥1.2 cm²); Inotropic reserve (SV increase ≥20%) stratifies operative risk sources/hemodynamics-circ-2012 high
• Nitroprusside challenge for low-flow/low-gradient AS (preserved LVEF): High peripheral resistance contributes to low CO; lowering afterload with vasodilators uncovers true severe AS (fixed valve area, rising gradient) sources/hemodynamics-circ-2012 high
• Cardiac output pitfall: assumed O₂ consumption tables introduce up to 40% Fick error; thermodilution unreliable in low-output states, TR, arrhythmias, or intracardiac shunts sources/hemodynamics-circ-2012 high

ACC/AHA 2020 — Asymptomatic AS Intervention Criteria

• Class I B-NR: LVEF <50% (Stage C2) → AVR
• Class IIa B-R: Very severe AS (Vmax ≥5 m/s) + low surgical risk → AVR reasonable
• Class IIa B-NR: Asymptomatic + BNP >3× normal + low risk → AVR reasonable
• Class IIa B-NR: Vmax progression ≥0.3 m/s/year + low risk → AVR reasonable
• Class IIa B-NR: Exercise-induced symptoms or ≥10 mmHg BP fall + low risk → AVR reasonable
• Class IIb B-NR: Progressive LVEF decline to <60% on ≥3 serial studies → AVR may be considered
• Note: ESC 2025 upgraded asymptomatic severe AS early intervention to Class IIa (broader criteria); ACC/AHA 2020 was more conservative with multiple Class IIa/IIb criteria sources/VHD-AHA-2020 very high

Perioperative Management of AS and NCS

• Severe symptomatic AS is one of the four "active cardiac conditions" warranting cardiac evaluation before any NCS (except emergency). (sources/periop-aha-2024, rating: very high)
• Evaluate for AVR before elevated-risk NCS (COR 2a): Symptomatic severe AS should be evaluated for aortic valve replacement (SAVR or TAVI) prior to elevated-risk elective NCS — see concepts/TAVI for NCS timing after TAVI. (sources/periop-aha-2024, rating: very high)
• Echo within 1 year: If prior echo exists and symptoms are unchanged, repeat echo is not routinely required within 1 year; however, any new symptoms or examination changes warrant reassessment before surgery. (sources/periop-aha-2024, rating: very high)
• Asymptomatic severe AS + preserved LVEF: Can safely proceed with low-risk NCS without prior valve intervention; elevated-risk NCS requires careful shared decision-making with cardiology input. (sources/periop-aha-2024, rating: very high)
• Balloon valvuloplasty as bridge (COR 2b): In patients with severe symptomatic AS who are not surgical candidates and require urgent NCS, percutaneous balloon aortic valvuloplasty may be considered as a temporising bridge — only if NCS cannot be deferred and TAVI is not immediately feasible. (sources/periop-aha-2024, rating: very high)
• Haemodynamic goals: Avoid hypotension (MAP <65 mmHg), tachycardia, and significant preload reduction; maintain sinus rhythm and adequate systemic vascular resistance to preserve coronary perfusion across the stenotic valve. (sources/periop-aha-2024, rating: very high)

Contradictions / Open Questions

• Long-term TAVI valve durability beyond 8–10 years is unknown — critical for decisions in younger patients
• Moderate AS + HFrEF: one small underpowered RCT; insufficient evidence for routine TAVI in this group
• Optimal timing and staging of PCI before TAVI remains unresolved (NOTION-3 vs ACTIVATION); no definitive guidance for moderate stenosis
• Whether routine early intervention in ALL asymptomatic low-risk patients is appropriate or over-treatment requires further RCT data
• ACC/AHA 2020 vs ESC 2025 asymptomatic AS divergence: ACC/AHA 2020 had fragmented criteria (multiple Class IIa/IIb); ESC 2025 introduced a single Class IIa for early intervention in appropriate patients (EARLY TAVR, RECOVERY, AVATAR, EVoLVeD meta-analysis) sources/VHD-AHA-2020 very high vs sources/vhd-esc-2025 very high
• ACC/AHA 2020 vs ESC 2025 TAVI age thresholds: ACC/AHA uses fixed age breakpoints (65/80 years); ESC 2025 uses Heart Team decision integrating age, life expectancy, and anatomical factors without fixed thresholds sources/VHD-AHA-2020 very high vs sources/vhd-esc-2025 very high

Connections

• Related to concepts/Valvular-Heart-Disease
• Related to concepts/TAVI
• Related to concepts/Structural-Valve-Deterioration
• Related to entities/ATTR-Amyloidosis
• Related to entities/Heart-Failure
• Related to concepts/Perioperative-Cardiovascular-Assessment
• Related to sources/periop-aha-2024

Sources

• sources/VHD-AHA-2020
• sources/hemodynamics-circ-2012
• sources/periop-aha-2024
• sources/vhd-esc-2025
• sources/vhd-mechanism-aha-2024