Hypoplastic left heart
This term describes an anomaly characterized by a variable degree of an underdeveloped, non-apex-forming left ventricle and stenosis/atresia of the mitral and aortic valves, consequently failing to support systemic circulation. This congenital cardiac lesion results in a univentricular circulatory system dependent on right ventricle performance and an open ductus arteriosus for perfusion. It is among the most common heart defects, with an estimated incidence of 0.16 to 0.36 per 1000 live births, accounting for 4.8% to 9% of CHDs56. The first description dates back to 1851 when von Bardeleben in 1851 described a severely ill newborn who died 27 weeks after birth from progressive heart failure. Postmortem examination revealed extremely diminished left heart structures and an atretic (obliterated) ascending aorta57,58. Interestingly, from a semantic perspective, HLH syndrome has been discussed to be a misnomer as it constitutes a heterogeneous, i.e., causally nonspecific, developmental field defect59. The most commonly held view regarding the development of HLH is postulated to be altered biomechanical stimuli (e.g., decreased ventricular filling resulting in reduced myocardial strains) during a critical period of ventricular development with advancing gestation60. Nonetheless, it has been hypothesized that the left ventricular hypoplasia might be caused by a primary defect in ventricular development. A recent study on postmortem HLH specimens suggested that the lesions seen represent acquired disease occurring following closure of the embryonic interventricular communication rather than sequelae of abnormal embryogenesis61. Morphologically, classic HLH comprises hearts with mitral and aortic valve atresia with an intact ventricular septum. On the other hand, there are variants of HLH characterized by different degrees of left heart obstruction with mitral atresia, a ventricular septal defect and a patent aortic valve or those with aortic valve atresia56,62. Recently, Crucean and colleagues described three distinct subgroups relying on the morphological appearance: (I) a slit-like LV (24%); (II) a miniaturized LV (6%); and (III) a thickened LV with endocardial fibroelastosis (EFE; 70%). Interestingly, only the slit-like ventricle grouping was found to map to the current nomenclature: the combination of mitral atresia with aortic atresia. Cases of a miniaturized LV all had normally formed, although small, aortic and mitral valves, and the last and predominating group was found to have a range of aortic valve malformations associated with thickened left ventricular walls despite being described as either atresia or stenosis62,63.
In a typical hypoplastic left heart condition, prenatal ultrasound shows a normally located right ventricle with a small hypocontractile LV often associated with hypoplasia of the ascending aorta. In contrast to CoA, the apex is formed by the RV, and there is markedly diminished LV function in order to support systemic circulation in HLH (see figure 4). As stated above, the shape and size of the LV can considerably vary (e.g., small, round, slit-like, dilated or even normal). In almost all cases, the aortic valve is atretic, but a common feature of HLH is an obstruction of both the LV inflow and outflow tracts in specific combinations of mitral valve (MV) atresia/aortic atresia (MA/AA), MV stenosis/aortic stenosis or MV stenosis/aortic atresia. The latter conditions account for nearly half of all HLH cases61. The left ventricular outflow is scarcely demonstrated in the 5CV/LVOT views during echocardiographic examination, as exemplified in figures 3 & 4. These figures further demonstrate a marked size discrepancy of the left atrium being smaller than the right atrium, with the flap of the foramen ovale excursing toward the RA as a consequence of the obstructed inflow. Notably, HLH may be accompanied by different degrees of foramen ovale restriction (up to 22%), potentially leading to chronic left atrial hypertension, which is transmitted onto pulmonary venous structures, resulting in pulmonary hypertension and remodeling. Jadcak et al. stated that an early appearance and a longer presence of FO obstruction rather than the extent of obstruction are associated with an increase in short-term mortality 64. Therefore, an additional thorough assessment of pulmonary venous (PV) Doppler (PVD) with a forward/reverse velocity-time integral (VTI) ratio of <3 has been found to be the strongest predictor of postnatal hemodynamic stability and the need for fetal intervention65. Despite a trend toward improved preoperative morbidity in neonates with a prenatal diagnosis of HLH, a recent systematic review revealed no significant impact on preoperative or postoperative Stage I mortality66. According to recent data from Richard et al., frequent serial fetal echocardiograms may not necessarily be needed to predict the need for an unexpected, emergent procedure67. However, this inevitably underscores the need for an exact delineation of the phenotypic features of the disease since hypoplasia of the left ventricle can be found in a number of other cardiac lesions (including an unbalanced AV canal, a double outlet right ventricle or a common arterial trunk). Moreover, borderline cases of HLH might be left undetected in many early to midgestation fetal exams and often tend to progress to HLH until birth.