Nearly 40 years have passed since the first palliation of a patient with hypoplastic left heart syndrome (HLHS). Since then, extensive research on this condition has shifted the prognosis from certain death to a modest hope for survival. HLHS encompasses a spectrum of disease scenarios, ranging from severe mitro-aortic atresia with aortic hypoplasia functioning as a conduit for coronary irrigation, to milder cases of mitral and/or aortic stenosis with underdevelopment of the left ventricle (LV). Thus, selecting patients for the various available therapies is crucial to reduce mortality associated with this pathology. Strategies vary from the staged repair proposed by Norwood (Norwood-Glenn-Fontan), hybrid techniques, to listing for heart transplantation in the fetal stage. Despite advancements, HLHS still presents high perioperative and interstage mortality, partly due to demanding functions from the right ventricle (RV), which it is not designed to perform.

Today’s article aims to provide a summary based on contemporary observations on RV remodeling throughout the different phases of HLHS repair. Remember, the RV is dominant during the fetal period due to ductus arteriosus permeability, allowing it to work against a similar afterload as an LV. Consequently, the RV in the neonatal period is larger and has a thicker wall than the LV. Following the closure of the ductus and a decrease in pulmonary resistance, the RV thins and assumes a morphology known as normal.

In a newborn with HLHS by aortic atresia, the RV is responsible for maintaining 100% of the combined cardiac output. A left-right shunt through the oval foramen is observed, allowing the RV to eject all blood through the pulmonary artery. However, due to continued high pulmonary resistance, blood is distributed to the systemic circuit. Retrogradely, it reaches the aortic arch and upper body, mimicking the fetal circulatory system.

During the first days of life, the Norwood surgery is performed; reconstructing the neo-aortic arch and connecting it with the pulmonary valve. Pulmonary flow is established via a Blalock-Taussig-Thomas shunt or by inserting a Sano conduit (RV-Pulmonary Artery). This connection to the pulmonary system increases the Qp/Qs ratio >1. The body’s homeostatic reflexes, aiming to maintain a Qs, result in RV volume overload, causing dilation. In this situation, the RV is exposed to systemic afterload and high preload due to an elevated Qp/Qs ratio, significantly increasing end-diastolic volume.

At 4-6 months of life, the first volume offloading intervention for the RV is performed: the bidirectional Glenn. In the bidirectional Glenn or bidirectional cavopulmonary connection, the systemic-pulmonary shunt from the neonatal period is tied off, and the superior vena cava is anastomosed to the right pulmonary artery. The inferior vena cava continues to preload the right atrium, and therefore the RV. This maneuver significantly reduces pulmonary flow, decreasing pulmonary venous return and RV preload. Thus, RV volume decreases, and its wall thickens. The Glenn surgery reduces preload and compliance of the RV by altering the telediastolic pressure-volume relationship. This results in a reduction of end-diastolic and systolic volumes. Subsequently, compensatorily, the relationship between telesystolic pressure and volume increases, restoring systolic volume in a context of reduced preload.

Finally, in the Fontan surgery or total cavopulmonary connection, the inferior vena cava is anastomosed to the right pulmonary artery. In this situation, all systemic return goes directly to the lungs, and the level of pulmonary pressure facilitates or limits ventricular preload and thus cardiac output. Remember, the RV is always under elevated telesystolic pressure as it is responsible for the systemic circuit. With the volume-pressure graphs in the article, the two mechanisms of a Fontan circulation failure are well understood. On one hand, we have failure with preserved ejection fraction where compliance decreases, resulting in increased telediastolic pressure. On the other hand, we have Fontan system failure with reduced ejection fraction, where contractility decreases, and due to compensatory mechanisms, results in increased diastolic volume and pressure.

COMMENTARY:

In evolution, humans have acquired a closed, double, and complete vascular circulatory system. Amphibians have a three-chambered heart similar to that of a fetus in its 5th week of development. As the fetus develops, its heart resembles that of some reptiles until complete septation of the circulatory system is achieved. When we perform the Fontan palliation, we recreate a univentricular situation seen in fish. It is far from an ideal solution, but it allows our patients to survive.

The case of HLHS is unique in nature; there is no other example in the animal kingdom where a right ventricle performs the functions of a systemic ventricle. This last statement might be disheartening, but the long journey undertaken by our predecessors in treating HLHS shows us that a systemic RV is possible. It’s not the best of solutions, but it allows rescuing patients who in other times were doomed, some even before birth. With the iconography of this exceptional article, we can understand the journey of the RV to become a systemic ventricle.

REFERENCE:

Salaets T, Gewillig M, Van De Bruaene A, Mertens LL. Right Ventricular Remodeling and Function in Hypoplastic Left Heart Syndrome. JACC Adv. 2024 Nov 20;3(12):101411. doi: 10.1016/j.jacadv.2024.101411.