HLHS Subtypes #1 – MS/AS (Mitral + Aortic Stenosis)

HLHS Subtypes – Mitral Stenosis / Aortic Stenosis (MS/AS)

The mitral-stenosis/aortic-stenosis (MS/AS) subtype is one of the common “classic” forms of hypoplastic left heart syndrome (HLHS) in contemporary surgical series, typically accounting for about 40% of cases undergoing Norwood-type palliation.[1] In the standard valve-based classification, HLHS is defined by the patency of the mitral (M) and aortic (A) valves (MA, MS, AS, AA), and MS/AS denotes a small but patent left ventricle with stenotic mitral and aortic valves.[2]

Compared with atresia variants, MS/AS is characterized by a discernible ascending aorta and a pressure-loaded, often fibroelastotic LV, which has important implications for both borderline two-ventricle decision-making and long-term outcomes.

1. Anatomic Features

1. Left ventricle (LV)
• The LV is small but present, with highly variable cavity size and wall thickness. Some patients have a nearly miniaturized LV with thin walls, whereas others have a thick-walled, hypertrophied chamber with a slit-like cavity.
• Endocardial fibroelastosis (EFE) is frequent in the mitral-stenosis subtypes (MS/AS and MS/AA).[3,8] In “peach-like” ventricles, the LV wall is markedly thickened and the endocardium is lined by dense fibroelastosis, in contrast to the “slit-like” LV of MA/AA.
• Pathologic and angiographic series suggest that the muscle bulk and myocardial damage of the rudimentary LV can influence systemic RV geometry and filling, particularly in MS/AA but also in some MS/AS hearts.[3,8]
2. Mitral valve – Mitral stenosis (MS)
• The mitral valve is stenotic rather than atretic: leaflets are often thickened, dysplastic, or partially fused; the subvalvar apparatus can be short or tethered.
• Diastolic inflow to the LV is restricted, elevating left-atrial and pulmonary venous pressures. A non-restrictive atrial communication (ASD or PFO) is therefore obligatory to decompress the left atrium and maintain pulmonary venous drainage.
3. Aortic valve – Aortic stenosis (AS)
• The aortic valve is patent but obstructed, with dysplastic, thickened, or fused leaflets producing significant outflow obstruction.
• A small but recognizable ascending aorta arises from the LV. In most MS/AS patients, the ascending aorta is larger than in aortic-atresia variants, reflecting some degree of fetal antegrade flow.[1,2]
4. Great vessels and ductus arteriosus
• The ascending aorta and arch are hypoplastic but better developed than in AA/MA and AA/MS.
• Systemic output at birth is a composite of:
• Antegrade flow across the stenotic aortic valve and hypoplastic ascending aorta, and
• Ductal-dependent flow from the RV → pulmonary artery → ductus arteriosus → descending aorta with retrograde perfusion of the arch.
• A patent ductus arteriosus (PDA) is therefore critical in the neonatal period until surgical or catheter-based palliation is established.
5. Right ventricle and atrial septum
• The right ventricle (RV) is the dominant functional ventricle and ultimately serves as the systemic ventricle in single-ventricle palliation.
• A wide ASD/PFO is essential. Restriction at the atrial level in an MS/AS heart can rapidly precipitate pulmonary venous hypertension and low cardiac output.

2. Hemodynamics and Pathophysiology

Because both inflow and outflow to the LV are stenotic, the effective LV stroke volume is highly variable:

• Antegrade systemic flow
• In some neonates, there is meaningful antegrade output through the stenotic aortic valve and ascending aorta, so systemic perfusion is a mixture of LV-derived and ductal flow.
• In others, antegrade LV output is minimal, and systemic circulation is almost entirely ductal, similar to atresia variants.
• LV pressure load and myocardial injury
• Chronic obstruction at the mitral and aortic valves exposes the small LV to high diastolic and systolic pressures, promoting hypertrophy, EFE, and myocardial necrosis or fibrosis.[3,8]
• Pathologic studies show that mitral-stenosis subtypes (MS/AA and MS/AS) have more frequent myocardial necrosis, calcification, and interstitial fibrosis than MA/AA.[3]
• This “stiff, thick-walled LV” can function as an inert mass within the ventricular septum, potentially impairing RV filling and wall motion, especially in the more extreme MS/AA phenotype.[3]
• Atrial and pulmonary venous hypertension
• Mitral stenosis elevates left atrial pressure; if the atrial septum is restrictive, this pressure is transmitted to the pulmonary veins and capillaries, increasing the risk of pulmonary edema and pulmonary vascular disease.

Physiologically, MS/AS spans a continuum from critical aortic stenosis with a borderline LV at one end to true single-ventricle HLHS at the other. The clinical task is to determine where a given patient lies along this spectrum.

3. Clinical Spectrum and Overlap with Critical Aortic Stenosis

3.1 Borderline left heart vs “classic” HLHS

• In some MS/AS infants:
• The LV cavity, although small, is near the lower limits of normal for body size.
• The mitral and aortic annuli are hypoplastic but potentially amenable to repair or enlargement.
• EFE is limited or absent, and the LV appears “miniaturized” rather than fibrotic.[8]
• These patients resemble critical aortic stenosis and are candidates for LV recruitment and eventual biventricular (BiV) repair.
• At the opposite extreme:
• The LV is tiny, heavily fibroelastotic, and contributes little effective stroke volume.
• Systemic output is almost entirely RV-to-ductal–dependent, with hemodynamics indistinguishable from MA/AA or AA/MS.
• For these patients, the LV behaves as a non-functional “peach-like” remnant, and a single-ventricle pathway is the only realistic option.[3,8]

3.2 Relationship to other anatomic subtypes

Early surgical series already suggested that outcomes after reconstruction varied by anatomic subtype. Jonas et al. reported that, among 78 HLHS patients, AS/MS had the most favorable 3-year survival (~76%), whereas AA/MA had the worst late outcome (~11% 3-year survival) after staged palliation.[4]

Subsequent work has refined this picture:

• Mitral stenosis–aortic atresia (MS/AA):
• Identified as a high-risk group with reduced RV volumes and impaired RV wall motion due to the bulky, damaged LV.[3]
• Vida et al. showed hospital mortality around 29% and a high incidence of transplant or death in MS/AA patients operated with a Norwood-type strategy, compared with ~8% hospital mortality in other subtypes.[5]
• Aortic atresia–mitral stenosis (AA/MS):
• Shuhaiber et al. analyzed 70 Norwood patients and found long-term survival of ~65% for AS/MS, ~60% for AA/MA, but only ~26% for AA/MS.[6]
• In a large Fontan cohort, Moon et al. demonstrated that AA/MS remained a long-term high-risk group, with significantly lower transplant-free survival into the second decade and higher rates of systemic ventricular failure compared with AA/MA and AS/MS.[8]

These data emphasize that left-sided pressure-loaded morphologies (particularly AA/MS and MS/AA) confer a sustained risk of systemic RV dysfunction and late failure. MS/AS generally fares better than AA/MS, but the subset of MS/AS patients with a thick, EFE-laden LV may behave more like the high-risk atresia variants.[3,6–8]

4. Surgical Strategy in MS/AS

Decision-making for MS/AS centers on LV adequacy and valve morphology. The same anatomic label can encompass patients suitable for BiV repair and those who clearly require single-ventricle palliation.

4.1 Candidates for two-ventricle (BiV) or LV-recruitment strategies

A minority of MS/AS patients have left-sided structures that can be recruited:

• LV end-diastolic volume near the lower limit of normal for body size.
• Mitral and aortic annuli that, although small, can be augmented surgically or relieved by valvotomy/valvuloplasty.
• Limited EFE and reasonable LV compliance.
• Acceptable pulmonary vascular resistance and absence of severe pulmonary venous disease.

In such patients, centers may pursue:

1. Neonatal or staged relief of valve stenosis
• Balloon or surgical aortic valvotomy to improve antegrade systemic flow.
• Surgical or catheter-based interventions for mitral stenosis, where anatomy permits.
2. LV decompression and “training”
• Ensuring adequate LV filling via atrial septal management.
• Progressive reduction of RV-to-systemic shunt dependence as the LV assumes more of the systemic workload.
3. Definitive BiV repair
• Once LV size, function, and outflow are deemed adequate, transition to standard biventricular circulation, sometimes with concomitant arch repair or residual valve interventions.

These strategies align with the broader move toward LV morphology-based decision-making, as emphasized in recent reviews of the left-ventricular myocardium in HLHS.[8]

4.2 Norwood-type single-ventricle pathway

For many MS/AS infants, the LV and valves are too small or too diseased to support a durable systemic circulation:

• Severely hypoplastic or fibroelastotic LV cavity.
• Mitral and aortic valves with critical stenosis and poor repair potential.
• Ascending aorta and arch significantly hypoplastic despite some antegrade flow.

In these patients, a Norwood-type Stage I operation followed by Glenn and Fontan remains the standard approach:

1. Stage I (Norwood)
• Reconstruction of a neo-aorta using the native pulmonary root and ascending aorta, with arch augmentation.
• The RV becomes the systemic ventricle, and controlled pulmonary blood flow is supplied via a modified Blalock-Taussig shunt or RV–PA conduit.
2. Stage II (Bidirectional Glenn)
• Superior vena cava connected to the pulmonary arteries, unloading the RV.
3. Stage III (Fontan completion)
• Total cavopulmonary connection, yielding a circulation where systemic venous return flows passively to the lungs and the RV supports only the systemic circuit.

Current outcome data show that AS/MS patients have intermediate to relatively favorable survival within the HLHS spectrum after Norwood–Fontan palliation, while AA/MS and MS/AA remain the highest-risk groups for ventricular and atrioventricular-valve failure.[5–8]

5. Practical Teaching Points for MS/AS

• Think in terms of LV morphology, not just valve labels.
• A “miniaturized” LV with thin walls and little EFE may be recruitable.
• A thick-walled, EFE-lined LV behaves like the high-risk AA/MS–MS/AA group.
• Assess the entire pathway.
• The impact of subtype differs at Norwood, interstage, and Fontan stages; MS/AS generally performs well early, but LV morphology and RV performance must be followed long-term.
• Counsel families about the continuum.
• Some MS/AS infants may reasonably be offered BiV or LV-recruitment pathways, but a substantial proportion still require traditional single-ventricle palliation.

References

[1] Sathanandam SK, Younoszai AK, Benscoter EM, et al. Mitral stenosis and aortic atresia in hypoplastic left heart syndrome: incidence, echocardiographic features, and outcome. Ann Thorac Surg. 2010;90(5):1543-1550.

[2] Tchervenkov CI, Jacobs JP, Weinberg PM, et al. The nomenclature, definition and classification of hypoplastic left heart syndrome. Cardiol Young. 2006;16(4):339-368.

[3] Sugiyama H, Yutani C, Iida K, et al. The relation between right ventricular function and left ventricular morphology in hypoplastic left heart syndrome: angiographic and pathological studies. Pediatr Cardiol. 1999;20(6):422-427.

[4] Jonas RA, Hansen DD, Cook N, Wessel D. Anatomic subtype and survival after reconstructive operation for hypoplastic left heart syndrome. J Thorac Cardiovasc Surg. 1994;107(4):1121-1127.

[5] Vida VL, Bacha EA, Larrazabal A, et al. Surgical outcome for patients with the mitral stenosis–aortic atresia variant of hypoplastic left heart syndrome. J Thorac Cardiovasc Surg. 2008;135(2):339-346.

[6] Shuhaiber J, Morgan B, Gottliebson W. Survival outcomes following Norwood procedure for hypoplastic left heart. Pediatr Cardiol. 2015;36(1):57-63.

[7] Fricke K, Mellander M, Sunnegårdh J, et al. Impact of left ventricular morphology on adverse outcomes in hypoplastic left heart syndrome. J Am Heart Assoc. 2022;11(5):e022929.

[8] Chaudhry B, Alqahtani A, Eley L, et al. The left ventricular myocardium in hypoplastic left heart syndrome. J Cardiovasc Dev Dis. 2022;9(8):279.

[9] Moon J, Lancaster T, Sood V, et al. Long-term impact of anatomic subtype in hypoplastic left heart syndrome after Fontan completion. J Thorac Cardiovasc Surg. 2024;168(1):193-201.e3.