Hypoplastic Left Ventricle: Hypoplastic Left Heart Complex

Guiding Principles of Nomenclature

One cannot define anatomy, morphology, and nomenclature of a cardiac phenotype by the type of treatment used, as treatment may evolve over time. As a case in point, the Norwood (Stage 1) Operation is in fact not synonymous with HLHS. In theory, it is possible to perform the Norwood (Stage 1) Operation on a normal neonatal heart, although in all practicality, such an operation would be unethical. Furthermore, the Norwood (Stage 1) Operation has been applied to complex cardiac malformations with two well-developed ventricles.

Understanding of the following terms is fundamental to the understanding of HLHS and HLHC^1,2:

Hypoplasia refers to the incomplete development or underdevelopment of a structure, but with relatively preserved geometry of the structure. The aortic valve, the mitral valve, and the left ventricle all may be hypoplastic.

Nomenclature for HLHS and HLHC

The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11) provide the following definition for HLHS^1–5:

Hypoplastic left heart syndrome (HLHS) is defined as “a spectrum of congenital cardiovascular malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch.”^1–5

Table 1 documents all of the subtypes of HLHS that are listed in The European Association for Cardio-Thoracic Surgery (EACTS) – Society of Thoracic Surgeons (STS) IPCCC Diagnosis Long List (https://ipccc.net/), accessed June 25, 2022.

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Table 1.

Subtypes of HLHS that are Listed in the EACTS-STS IPCCC Diagnosis Long List (https://ipccc.net/), accessed June 25, 2022.

HLHS

HLHS, aortic atresia + mitral atresia

HLHS, aortic atresia + mitral stenosis

HLHS, aortic atresia + mitral stenosis, IVS

HLHS, aortic atresia + mitral stenosis, VSD

HLHS, aortic atresia + mitral stenosis, VSD, nonrestrictive VSD

HLHS, aortic atresia + mitral stenosis, VSD, restrictive VSD

HLHS, aortic stenosis + mitral atresia

HLHS, aortic stenosis + mitral atresia, nonrestrictive VSD

HLHS, aortic stenosis + mitral atresia, restrictive VSD

HLHS, aortic stenosis + mitral stenosis

HLHS, aortic stenosis + mitral stenosis, IVS

HLHS, aortic stenosis + mitral stenosis, VSD

HLHS, aortic stenosis + mitral stenosis, VSD, nonrestrictive VSD

HLHS, aortic stenosis + mitral stenosis, VSD, restrictive VSD

HLHS, aortic stenosis + MV hypoplasia

HLHS, aortic stenosis + MV hypoplasia, IVS

HLHS, aortic stenosis + MV hypoplasia, VSD

HLHS, aortic stenosis + MV hypoplasia, VSD, nonrestrictive VSD

HLHS, aortic stenosis + MV hypoplasia, VSD, restrictive VSD

HLHS, without intrinsic valvar stenosis or atresia (hypoplastic aortic valve + mitral valve + left ventricle) (HLHC)

HLHS, without intrinsic valvar stenosis or atresia (hypoplastic aortic valve + mitral valve + left ventricle) (HLHC), IVS

HLHS, without intrinsic valvar stenosis or atresia (hypoplastic aortic valve + mitral valve + left ventricle) (HLHC), VSD

HLHS, without intrinsic valvar stenosis or atresia (hypoplastic aortic valve + mitral valve + left ventricle) (HLHC), VSD, nonrestrictive VSD

HLHS, without intrinsic valvar stenosis or atresia (hypoplastic aortic valve + mitral valve + left ventricle) (HLHC), VSD, restrictive VSD

Abbreviations: HLHC, hypoplastic left heart complex; HLHS, hypoplastic left heart syndrome; IVS, interventricular septum; MV, mitral valve; VSD, ventricular septal defect.

The spectrum of HLHS, as proposed by The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), is summarized in Table 1. Whereas the severe end of the HLHS spectrum consists of those patients with aortic and mitral atresia, the mild end of the HLHS spectrum consists of patients with HLHC.

The IPCCC provides the following definition for HLHC ² :

“Hypoplastic left heart syndrome without intrinsic valvar stenosis or atresia is synonymous with the term hypoplastic left heart complex and is defined as a cardiac malformation at the milder end of the spectrum of hypoplastic left heart syndrome with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle and hypoplasia of the aortic or mitral valve, or both valves, in the absence of intrinsic valvar stenosis or atresia, and with hypoplasia of the ascending aorta and aortic arch.” ²

Critical Aortic Stenosis Versus HLHC

Generally, many HLHC patients with hypoplasia of the aortic valve, mitral valve, and left ventricle may be candidates for biventricular repair, while those with true aortic and mitral stenosis are less likely to be. It is thus important to distinguish those patients with critical aortic stenosis from those with HLHC (Table 2).

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Table 2.

Comparison of HLHC and Critical AS With LV Hypoplasia.

Critical AS + LV hypoplasia	HLHC
Thickened leaflets Commissural fusion Need for aortic valvotomy Biventricular repair: <50% Scoring systems: Rhodes CHSS Colan	Hypoplastic, but normal leaflets Normal leaflet function No need for aortic valvotomy Biventricular repair: >90% Physiologic considerations

Abbreviations: AS, aortic stenosis; CHSS, Congenital Heart Surgeons’ Society; HLHC, hypoplastic left heart complex; LV, left ventricle.

In HLHC, the valve leaflets are hypoplastic but normal, and there is normal valve function. In such situations, aortic valvotomy by surgical or percutaneous means is not necessary. On the other hand, patients with critical aortic stenosis have thickened aortic valve leaflets and/or commissural fusion which require aortic valvotomy. Due to the severity of obstruction in many patients with aortic valvar stenosis, the left ventricle tends to be less compliant than seen in the left ventricle in HLHC. Several scoring systems have been applied to critical aortic stenosis with left ventricular hypoplasia to aid in determining whether certain patients would be candidates for biventricular repair, including the Rhodes score, ⁹ Colan score, ¹⁰ and the Congenital Heart Surgeons’ Society (CHSS) risk calculator, ¹¹ but these scoring systems are not applicable to HLHC. ¹² Endocardial fibroelastosis (EFE), a negative predictor of successful biventricular repair in critical aortic stenosis with left ventricular hypoplasia, tends to not be present in HLHC.

Imaging Assessment of HLHC

Accurate assessment of the size and function of the individual components of the left heart-aorta complex is vital to determining candidacy for biventricular repair. In addition to an assessment of the mitral valve, left ventricle, LVOT, aortic valve, ascending aorta, and aortic arch, the presence or absence of aortic coarctation must be confirmed. The diagnosis of HLHC should be established with the lack of valvar stenosis or atresia. In conjunction with a structural assessment, it is important to determine the physiological consequence of the hypoplastic structures as a whole.

To this end, echocardiography is the mainstay diagnostic tool for evaluation. Relevant echocardiographic measurements include:

the size and z-score of the mitral valve,

It is important to not rush into the decision of taking a biventricular versus univentricular strategy. To this end, serial echocardiography is warranted in the immediate postnatal period. As pulmonary vascular resistance falls, the blood flows into the ascending aorta and aortic arch may also change, which in turn can impact the potential of the hypoplastic left ventricle to grow. What was initially retrograde flow into the ascending aorta and aortic arch from ductal-dependent systemic circulation may eventually become consistently antegrade flow from the left ventricle. Initially, a suboptimal left ventricular function may normalize during this period as well. Maintaining the patent ductus arteriosus with prostaglandin while continuing to monitor the patient for any physiological improvements is a viable strategy prior to deciding on univentricular palliation versus biventricular repair.

Magnetic resonance imaging (MRI) has seen increased use in the assessment of patients with HLHS and HLHC. In fact, MRI may have advantages in comparison to echocardiography in some situations where the severity of left ventricular hypoplasia is borderline for biventricular repair. Grosse-Wortmann et al ¹⁴ compared the usefulness of preoperative MRI and echocardiography in patients with borderline small left ventricles in 20 patients, 12 of whom were diagnosed with HLHC. Echocardiography consistently underestimated left ventricular volume and did not correlate with MRI. An indexed LVEDV of more than 20 mL/m² has commonly been considered as one of the cut-offs for successful biventricular repair, yet only 31.3% of this cohort met this criterion and went on to have successful biventricular repair. The investigators thus concluded that echocardiography may falsely exclude some patients for whom MRI measurements are more reassuring. MRI can also evaluate the extent of EFE.

Criteria for Biventricular Repair in HLHC

Based on the experience at the Montreal Children's Hospital, successful biventricular repair in HLHC is contingent on several criteria, which are not simply dependent on absolute imaging measurements. Forward flow through the left heart into the ascending aorta and aortic arch branches is required. Occasionally, a patient may have flow reversal in the early neonatal period, but eventually, the patient must have consistent antegrade flow. Implicit to the definition of HLHC, the patient should not have intrinsic stenosis (or atresia) of the aortic valve or mitral valve. The patient should have an adequate left ventricular function to sustain the systemic circulation and withstand systemic afterload. Finally, EFE should not be present.

Principles and Technique of Biventricular Repair in HLHC

The key principles of biventricular repair of HLHC are as follows:

Elimination of all extracardiac afterload by enlargement of the ascending aorta and aortic arch (Figure 1A and Figure 1B). The proximal extent of the aortic augmentation should not extend into the aortic root in order to avoid injury to the coronary arteries. The distal extent of the aortic augmentation should extend into the proximal descending thoracic aorta.

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Figure 1.

Techniques of biventricular repair of HLHC. Figure 1 was drawn by Richard Tang, MD. (A) The hypoplastic aortic arch and ascending aorta are opened longitudinally. (B) Patch augmentation of the ascending aorta and aortic arch is performed. (C) Interatrial communications are closed. In some patients with borderline left ventricular function, a two to three mm interatrial fenestration is left in place.

At Montreal Children's Hospital, all patients were approached by median sternotomy, and repairs were conducted on cardiopulmonary bypass under deep hypothermia. The hypoplastic ascending aorta was cannulated at the base of the brachiocephalic artery along the lateral side, and bicaval cannulation was utilized. The patent ductus arteriosus was suture ligated while cooling. When deep hypothermia was achieved, selective antegrade cerebral perfusion was achieved by advancing the aortic cannula into the brachiocephalic artery and snaring it in place, while snaring the other head vessels, and perfusing the brachiocephalic artery under low flow. The lesser curvature of the ascending aorta and aortic arch was incised and opened longitudinally from the proximal ascending aorta to the proximal descending thoracic aorta. The opened aorta was then augmented with a patch of pulmonary homograft. Any interatrial or interventricular communications were closed via a right atriotomy. In some patients, a two to three mm interatrial fenestration was left in place.

In some patients with HLHC, the feasibility of biventricular repair may be unclear. In these situations, staged left ventricular recruitment may lead to growth of the left heart structures for later biventricular conversion, as demonstrated by the Boston group. ¹⁵ In staged left ventricular recruitment, adjunct methods, such as ASD restriction, are applied to the traditional pathway of univentricular palliation in an effort to rehabilitate the left heart until it is near normal in size and function, prior to takedown of aortopulmonary shunts and/or cavopulmonary anastomoses and reestablishing separate left and right ventricular outflow tract continuities. At Montreal Children's Hospital, in a minority of patients, the VSD was not closed at the initial operation that involved augmenting the aortic arch and ascending aorta and placing a pulmonary artery band (PAB). After adequate growth of the left ventricle, the VSD was closed several months later along with removal of the PAB.

The Giessen hybrid strategy is an alternative approach for neonates not initially clearly suitable for biventricular repair. Stage 1 involves bilateral banding of the branch pulmonary arteries and maintaining the ductus arteriosus open with a stent or prostaglandin as initial palliation. This strategy serves as a “bridge to decision,” permitting the patient to grow for four to six months before deciding if a patient is suitable for either committing to the univentricular pathway (i.e., Giessen stage 2, which involves a Norwood-type procedure and superior cavopulmonary connection) or biventricular repair. Yerebakan et al ¹⁶ utilized this approach in their cohort of patients with HLHS, in which a majority were patients with HLHC, with satisfactory long-term survival.

Postoperative Course

After neonatal biventricular repair, the left heart can successfully support the systemic circulation in more than 90% of patients with HLHC. ⁶ For those with successful biventricular repair, significant enlargement of left heart structures can be seen even prior to discharge. ⁶ As demonstrated in several series,^17–19 tremendous catch-up growth of left heart structures occurs within the first six months to the first year of life, with a lower growth rate of the mitral valve compared to other structures.

Early and Late Survival

Early mortality, according to various series, ranges from 6% to 15%^6,17–19 for initial biventricular repair. Patients who first underwent left ventricular recruitment or hybrid strategies had similar rates.^14,15 Causes of death varied by series, and some patients died from noncardiac complications.

Patients with successful biventricular repair go on to have favorable long-term survival. Tchervenkov et al ⁶ demonstrated only one late death at 39 months after repair, out of 11 patients who survived to discharge from the hospital, with a mean follow-up of 67 months. This one patient had pulmonary hypertension along with a single right coronary artery and died following a modified Konno operation. Bergonzini et al ¹⁸ reported 30 patients with HLHC who underwent biventricular repair with one late mortality due to extracardiac complications after a mean follow-up of 63 months. In the series reported by Ijsselhof et al, ¹⁹ 30 of 32 patients who underwent biventricular repair survived to discharge from the hospital, and all were alive at 10-year follow-up.

Reoperations

Regardless of whether patients with HLHC received neonatal or delayed biventricular repair, these patients are prone to requiring reinterventions.^6,15–19 Freedom from reoperation or transcatheter intervention drops to almost 40% by 5 years. ¹⁸ Balloon aortoplasty has been performed in up to 30% of patients. ¹⁹ Recoarctations and the development of LVOT obstruction (LVOTO) were the most common reasons for reoperation, requiring repair of the ascending aorta and/or aortic arch, root enlargement procedures, and/or aortic valve repair and/or replacement.