Introduction Left ventricular non-compaction (LVNC) is characterized by excessive trabeculations of the left ventricular wall. LVNC may be associated with reduced systolic function but is also found in individuals with normal ventricular function. It is debated whether LVNC is only congenital or may develop later in life. The clinical importance and heredity of LVNC with normal systolic function is unclear. Purpose We aimed to describe the echocardiographic development of the left ventricular function and LVNC pattern in children with LVNC, diagnosed at birth, at follow-up at the age of 2–4 years compared to matched controls. Additionally, we aimed to describe the prevalence of LVNC in first-degree relatives. Methods A follow-up transthoracic echocardiography was performed in children at 2–4 years of age, diagnosed with LVNC at birth (<30 days) as part of a large population study of newborns (n>25,000). Cases were matched 1:4 to controls on mother's age at delivery, parity, and age of the child at follow-up. First-degree relatives (parents, siblings and half-siblings) of cases and controls were also offered inclusion. LVNC was defined as a ratio of non-compact to compact myocardium of ≥2 in at least one left ventricular segment measured in end-diastole perpendicular to the left ventricular cavity. Results 13 of the 16 children diagnosed with LVNC at birth (median age 3 (interquartile range (IQR) 3–4) years, 77% male) and 52 children without LVNC at birth (age 4 (IQR 3–4) years, 88% male) was reevaluated as well as 36 first-degree relatives of children with LVNC (age 30 (IQR 4–37) years, 44% male) and 136 first-degree relatives of children without LVNC (age 32 (IQR 10–38) years, 50% male). In probands, the number of segments fulfilling criteria (8% vs. 13%, p=0.4) and systolic function, measured as fractional shortening (FS), were unchanged from birth to follow-up, and within normal range (29% vs. 30%, p=0.34). However, at follow-up, FS was significantly lower in probands compared with matched controls (30% vs. 33%, p<0.001). Criteria of LVNC was fulfilled in 11 out of 36 (31%) first-degree relatives to probands, whereas none of the first-degree relatives of children without LVNC fulfilled criteria of LVNC (p<0.001). FS was significantly lower in first-degree relatives of probands fulfilling criteria of LVNC compared to first-degree relatives of matched controls (30% vs. 32%, p=0.01). Conclusion Children with LVNC diagnosed neonatally as part of a population study still had a reduced systolic function when compared to controls but showed no further progression of left ventricular dysfunction or extent of trabeculation at the age of 2–4 years. One third of first-degree relatives to children diagnosed with LVNC with a preserved systolic function, fulfilled criteria for LVNC and had reduced systolic function compared to controls. These findings strongly support family-screening and clinical follow-up of children with LVNC. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Novo Nordisk FoundationHerlev-Gentofte Hospital Internal Funding

Background Mitral valve abnormalities (MVA) include mitral valve regurgitation (MR), mitral valve prolapse (MVP), Barlow's mitral valve disease, and parachute MV. The prevalence of MVA has yet to be determined in an unselected population of newborns. Objective To determine the prevalence of MVA in unselected newborns and to assess the left ventricular (LV) structure and function in the neonatal heart with MR. Methods Transthoracic echocardiography (TTE) was performed within 28 days after birth in unselected neonates consecutively included in a prospective, multicenter, population-based study (2016–2018 (n=25,751)). TTE's were systematically reviewed for MR, MVP, Barlow's MV disease, and parachute MV. In a subgroup of 400 newborns with MR, the regurgitation was further classified as either traceable MR, mild MR, or moderate/severe MR based on the ratio of the trans-mitral jet in systole over the diastolic filling duration using M-mode in the 4-chamber view of the LV. Results Of 25,751 included newborns, we found a prevalence of MVA of 26.7%. (6,883/ 25,751). The prevalence of MR was 26.2%, MVP was 0.35%, Barlow's disease was 0.13%, and parachute mitral valve was 0.027%. MR was more frequent in females compared to males (50.4 vs 48.2%, p<0.01). Newborns with MR had enlarged left atrial diameter (11.91±2.03 mm vs 11.53±2.02 mm, p<0.01) and LV end-diastolic and end-systolic diameter (LVIDd 19.98±1.88 mm vs 19.87±1.83 mm, p<0.01, LVIDs 13.48±1.47 mm vs 13.31±1.41 mm, p<0.01), thicker LV posterior wall (2.19±0.60 mm vs 2.05±0.52 mm, p<0.01), increased early and atrial mitral inflow velocities (MV E velocity (0.65±0.14 m/sec vs 0.61±0.13 m/sec, p<0.01), MV A velocity (0.60±0.13 m/sec vs 0.57±0.13 m/sec, p<0.01)), but lower fractional shortening (32.54±4.22% vs. 32.96±4.17%, p<0.01) as compared to newborns without MVA. In subgroup analysis MR severity was classified as traceable in 44% (175/400) of cases, mild MR in 52% (209/400) of cases and moderate/severe MR in 4% (16/400) of cases. Comparing traceable MR with moderate/severe MR (19.48±1.88 mm vs 20.96±2.64 mm, p=0.01) and comparing mild MR with moderate/severe MR (19.85±1.92 mm vs 20.96±2.64 mm, p=0.04) showed significant increases in LV end-diastolic diameter. Conclusion Over one fourth of all newborns had a MV abnormality of which mitral regurgitation accounted for the vast majority. The presence of MR was associated with asymmetric LV remodeling and discrete changes in LV function. Subgroup analysis revealed that increment in MR severity was primarily associated with an increase in LV end-diastolic diameter. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Herlev-Gentofte Hospital

Background Congenital aortic valve regurgitation (AVR) has been estimated to be present in 0.25 per 1,000 live births globally. The true prevalence in an unselected large-scale cohort remains unknown. Presence of congenital AVR could indicate a structural valve abnormality and may result in long-term strain on the heart. Aim To find the true prevalence of AVR in a large cohort of unselected newborns. Methods Between April 2016 and October 2018, 25,752 newborns were consecutively included in a population-based prospective multicenter cohort and examined with transthoracic echocardiography within the first 30 days of life. Examinations with AVR were categorized as trivial AVR by the presence of a trivial diastolic transvalvular flow, or as non-trivial AVR by the presence of a significantly larger and visually observable transvalvular flow. In newborns with non-trivial AVR, the vena contracta, the duration of the transvalvular flow, and the duration of the diastole were measured. The cases were matched 1:4 with newborns with no AVR based on sex, gestational age at birth, birth weight and age at time of examination. Results AVR was identified in 329 newborns (1.3%). Of these, 260 were classified as trivial AVR, 69 (0.27%) were non-trivial AVR. Non-trivial AVR had significantly larger aortic roots at all points of measurement compared to controls (mean±SD): aortic valve annulus (7.3 (0.73) vs. 7.0 (0.63) mm), Sinus of Valsalva (10.3 (1.0) vs. 9.7 (1.0) mm), sino-tubular junction (8.4 (0.8) vs. 8 (0.8) mm), and ascending aorta (10 (0.9) vs. 9.4 (1.1) mm) (p<0.01 for all). Left ventricular dimensions and function did not significantly differ between the cases and controls. The presence of a non-trivial AVR was highly associated with a bicuspid aortic valve (9 (13.0%) vs. 3 (1.1%), p<0.001). Conclusions We found a prevalence of congenital AVR of 1.3% in a large cohort of unselected newborns, which is higher than previously reported. One in five of all AVR found were classified as non-trivial. Newborns with non-trivial AVR presented with larger aortic root and ascending aorta dimensions. Newborns with non-trivial AVR also had a ten-fold higher occurrence of bicuspid aortic valve compared to controls. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Hjerteforeningen

Introduction: Left ventricular non-compaction (LVNC) is characterized by excessive trabeculations of the left ventricular wall and may be associated with reduced systolic function. It is debated whether LVNC is congenital or may develop later as part of other cardiomyopathies. The clinical importance and heredity of LVNC with normal systolic function is unclear. We aimed to describe the cardiac development in children with LVNC from birth to 2-4 years of age, compared to matched controls. Additionally, we aimed to describe the prevalence of LVNC in first-degree relatives. Methods: A follow-up transthoracic echocardiography was performed in children at 2-4 years of age diagnosed with LVNC at birth (<30 days) in the Copenhagen Baby Heart Study. Cases were matched to controls on mothers age at delivery, parity, and age of child at follow-up. First-degree relatives (parents, siblings and half-siblings) were also included. LVNC was defined as a non-compact to compact ratio of myocardium of ≥2 in at least one left ventricular segment, measured in 24 segments in end-diastole perpendicular to the left ventricular cavity as previously suggested. Results: Of the 16 children diagnosed with LVNC at birth, 10 have been reevaluated (age 3.5 (interquartile range (IQR) 3, 4) years, 80% male) together with 20 matched controls (age 4 (IQR 3, 4) years, 70% male), 29 first-degree relatives in case group (age 29 (IQR 4, 35) years, 45% male) and 55 first-degree relatives in control group (age 32 (IQR 11, 36) years, 51% male). In probands, the extent of trabeculation (13% vs. 12%, p=0.97) and fractional shortening (FS) (29% vs. 31%, p=0.24) were unchanged from birth to follow-up. At follow-up, the median left ventricular FS was significantly lower in probands compared to matched controls (31% vs. 33%, p=0.03). Ten (35%) first-degree relatives to probands fulfilled criteria for LVNC compared to 0 (0%) of first-degree relatives to controls (p<0.001). Conclusions: Children with LVNC diagnosed neonatally as part of a population study had no further progression of left ventricular dysfunction or extent of trabeculation at the age of 2-4 years, but systolic function was reduced compared to matched controls. One third of first-degree relatives to children with LVNC fulfilled criteria for LVNC.