An Extremely Rare Congenital Association: Uni- cuspid Aortic Valve with Left Ventricular Noncom- paction (RCD code: III-5A.1.o)

Commentary: Standardized aortic valve repair in pediatric patients

In this issue of Circulation , Klaassen and colleagues1 describe mutations in the genes encoding myosin heavy chain (MHC), cardiac actin, and troponin T in patients with left ventricular noncompaction (LVNC). LVNC, defined as excessive and unusual trabeculation of the mature left ventricle, is thought to reflect a developmental failure of the heart to form fully the compact myocardium during the later stages of cardiac development. Previously, mutations in sarcomeric genes have been linked extensively to the development of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The finding of similar, but not identical, mutations in patients with LVNC suggests a continuum of cardiomyopathy that includes LVNC and further supports the essential role for normal sarcomere function during cardiac development. Article p 2893 Noncompaction of the ventricular myocardium is characterized by a spongy morphological appearance of the myocardium occurring primarily in the left ventricle and most evident in the apical portion.2 Noncompaction often is visualized as deep recesses within the thickened apex, and these sinusoids communicate with the ventricular cavity. During heart development, the myocardium is initially trabeculated during a period before coronary artery development and is thought to be an adaptation to provide blood flow to the developing myocardium. The development of the coronary vasculature is associated temporally with the loss of trabeculae and the full maturation of the compact myocardium. Between embryonic weeks 5 and 8, the trabeculae regress as the compact myocardium develops from base to apex. Isolated LVNC is defined as occurring in the absence of other cardiac structural malformation. Nonsyndromic LVNC refers to the absence of other extracardiac developmental disorders. In 2006, the American Heart Association scientific statement on classification of cardiomyopathies reclassified LVNC as its own disease entity.3 Klaassen et al now link genetic sarcomere defects to both familial and sporadic isolated, …

Left ventricular (LV) noncompaction (LVNC) is a distinct cardiomyopathy featuring a thickened bilayered LV wall consisting of a thick endocardial layer with prominent intertrabecular recesses with a thin, compact epicardial layer. Similar to hypertrophic and dilated cardiomyopathy, LVNC is genetically heterogeneous and was recently associated with mutations in sarcomere genes. To contribute to the genetic classification for LVNC, a systematic cardiological family study was performed in a cohort of 58 consecutively diagnosed and molecularly screened patients with isolated LVNC (49 adults and 9 children). Combined molecular testing and cardiological family screening revealed that 67% of LVNC is genetic. Cardiological screening with electrocardiography and echocardiography of 194 relatives from 50 unrelated LVNC probands revealed familial cardiomyopathy in 32 families (64%), including LVNC, hypertrophic cardiomyopathy, and dilated cardiomyopathy. Sixty-three percent of the relatives newly diagnosed with cardiomyopathy were asymptomatic. Of 17 asymptomatic relatives with a mutation, 9 had noncompaction cardiomyopathy. In 8 carriers, nonpenetrance was observed. This may explain that 44% (14 of 32) of familial disease remained undetected by ascertainment of family history before cardiological family screening. The molecular screening of 17 genes identified mutations in 11 genes in 41% (23 of 56) tested probands, 35% (17 of 48) adults and 6 of 8 children. In 18 families, single mutations were transmitted in an autosomal dominant mode. Two adults and 2 children were compound or double heterozygous for 2 different mutations. One adult proband had 3 mutations. In 50% (16 of 32) of familial LVNC, the genetic defect remained inconclusive. LVNC is predominantly a genetic cardiomyopathy with variable presentation ranging from asymptomatic to severe. Accordingly, the diagnosis of LVNC requires genetic counseling, DNA diagnostics, and cardiological family screening.

Unicuspid aortic valve (UAV) is a rare congenital anomaly that usually presents with aortic stenosis or mixed stenosis and regurgitation early in life. Ascending aortic aneurysm and aortic dissection are important complications of UAVs. A 27-year-old man presented to the emergency department with a complaint of acute chest pain. Bedside transthoracic echocardiography (TTE) showed dilatation of ascending aorta (47 mm) and mild aortic regurgitation; computed tomography (CT) angiography revealed a suspicious dissection flap within ascending aorta. A cardiovascular surgeon, a radiologist, and a cardiologist were immediately consulted. TTE performed by the cardiologist revealed a unicuspid unicommissural aortic valve and dilated ascending aorta with no signs of dissection. Aortic dissection image on CT angiogram was interpreted by an experienced radiologist and the cardiovascular surgeon as superior pericardial recess and considered as a false-positive dissection image. Given the patient was pain-free, the CT image was considered false positive and as TTE clearly visualized the ascending aorta, the heart team decided that no further imaging is required. After excluding acute aortic syndrome, acute coronary syndrome, and other causes of acute chest pain, the patient was discharged with close follow-up. Diagnosis of aortic dissection is based on noninvasive imaging modalities, and CT is the first-line imaging choice in most emergency departments. Depending on a single imaging modality may cause false interpretations and lead to unnecessary surgical explorations.

Transesophageal Echocardiography of a Unicuspid Aortic Valve

Approximately, 75% of patients with infective endocarditis have underlying structural heart disease at the time of diagnosis. Aortic valve disease is associated with up to a quarter of patients, with aortic regurgitation being the most common abnormality. A unicuspid aortic valve (UAV) is an extremely rare congenital anomaly with a prevalence of 0.02%. We present a unique case of UAV with a devastating association. Case Summary: A 32-year-old male intravenous drug abuser presented with weakness after 18-hours of symptom onset. He was afebrile but tachycardic, with left-sided hemiparesis and sensory loss. Brain CT-scan revealed a hypodensity within the right cerebral hemisphere, a CTA of head-neck revealed an acute right MCA infarct with malignant cerebral edema. Due to deteriorating clinical condition, he was intubated for airway protection and underwent emergent hemi-craniectomy. Blood cultures grew enterococcus faecalis. Transthoracic echocardiogram showed abnormal aortic valve with severe regurgitation. Transesophageal echocardiography (TEE) demonstrated unicuspid unicommissural aortic valve with a small mobile echodensity attached to the left ventricular outflow tract aspect. Decision Making: He received a 6-weeks course of ceftriaxone and vancomycin with negative repeat blood cultures. Given poor clinical state, he was deemed poor candidate for valve replacement and was discharged to long-term rehabilitation facility. Four-months later, he was re-admitted with fevers. Repeat TEE demonstrated multiple aortic valve vegetations. He subsequently underwent successful minimally invasive aortic valve replacement. Conclusion: Unicuspid unicommisural aortic valve is an extremely rare condition that can be complicated by aortic stenosis more often than regurgitation. Infective endocarditis has been reported in 11% among UAV patients and can lead to valvular destruction with severe regurgitation which can be catastrophic in some patients

OP-001 UNICUSPID AORTIC VALVE DUE TO CHRONIC INFECTIVE ENDOCARDITIS: A CASE REPORT

Funding Acknowledgements This study was supported by Ministry of Health of the Czech Republic 17-28265A Introduction Management of asymptomatic patients with chronic severe aortic regurgitation (AR) is challenging. Reliable quantification of the AR severity is essential. Transthoracic echocardiography (TTE) is a primary imaging modality. Grading of AR severity is achieved by an integrative approach. Cardiovascular magnetic resonance (CMR) can directly quantify AR severity by measuring regurgitation volume (RV) and regurgitation fraction (RF). Purpose There are few data on direct comparison between TTE and CMR for quantification of AR. Our study aimed to compare quantitative and indirect echo-Doppler indices to quantitative MRI derived parameters in asymptomatic patients with severe chronic AR. Methods In a prospective three-centre study, we evaluated patients with moderate to severe (3+) and severe (4+) chronic AR using TTE and CMR. All patients were asymptomatic, without indication for surgical treatment. The severity of AR was graded using TTE multiparametric approach. A 2-D and 3-D TTE were performed with an assessment of left ventricle size and function, valve morphology, Doppler parameters of AR including vena contracta width, diastolic flow reversal velocity in descending aorta, RV, RF using volumetric method, 3D-vena contracta area (3D-VCA). The CMR quantified left ventricle volumes and function, RF and RV using the phase-contrast velocity mapping. All imaging studies were analysed in CoreLab. Results A total of 104 patients were enrolled during 2015-2018. Mean patient age was 44 ± 13 years, 89 patients (86%) were males and 83 patients (81%) had a bicuspid or unicuspid aortic valve. Using the TTE severe (4+) AR was present in 48 (46%) and moderate to severe (3+) AR in 56 (54%) individuals. Concordant grading of AR severity with both techniques was observed in 77 (74%) patients. An integrative TTE approach showed a trend to underestimate AR severity. The best correlation between echo-Doppler indices and CMR measured RV and RF was found in two parameters: diastolic flow reversal velocity in descending aorta ( Rs = 0,62, p < 0,0001 for RV, Rs = 0,50, p < 0,0001 for RF) and 3D-VCA (Rs = 0,48 for RV, p < 0,0001 , Rs = 0,38 for RF, p < 0,0001). On the contrary vena contracta width showed poor correlation with CMR (Rs = 0,18, p = 0,07 for RV and Rs = 0,11, p = 0,29 for RF). Correlation between quantitative parameters of AR assessed by TTE volumetric method and CMR technique was modest (Rs = 0,40 for RF and Rs = 0,50 for RV, p < 0,0001), 95% confidence intervals were wide. Good correlation between TTE and CMR were found for LV dimensions, volumes and ejection fraction. Conclusion Out of indirect Doppler-echo indices of AR severity, diastolic flow reversal velocity in descending aorta and 3D-vena contracta area showed the best correlation with MRI derived RF and RV in patients with chronic severe AR. Quantitative parameters of AR (RF and RV) assessed by echo volumetric method had an only modest correlation to RF and RV measured using CMR.

GATA5 and Endothelial Nitric Oxide Synthase Expression in the Ascending Aorta Is Related to Aortic Size and Valve Morphology

BackgroundLeft ventricular noncompaction (LVNC) is a rare congenital abnormality. It is currently classified as a genetic cardiomyopathy and results from early arrest of endomyocardial morphogenesis. The pathophysiology of left ventricular dysfunction, which becomes apparent beyond the 4th decade of life, is unclear.Case reportWe report a case of 60-year-old woman who presented with shortness of breath and showed noncompacted endocardium on echocardiography. Cardiac catheterization and viral studies were unremarkable. Histology revealed endomyocardial fibrosis without disarray. She was subsequently diagnosed with LVNC and treated with medications.DiscussionCardiologists and other physicians should be aware of LVNC due to its high likelihood of misdiagnosis and associated high complication rates. Early diagnosis, intervention and screening among family members can decrease the morbidity and mortality associated with LVNC.

BackgroundA unicuspid aortic valve is a rare congenital cardiac abnormality. Despite its uncommon finding on an initial presentation, aortic insufficiency is accompanied with unicuspid aortic valve and this might reflect the natural history of progression in the morphology of unicuspid aortic valve.Case presentationWe describe a 65-year-old Japanese man who was evaluated for endocarditis and found to have a unicuspid aortic valve concomitant with moderate aortic insufficiency, which was, owing to the lack of evidence of valve membrane destruction, independent of underlying infectious endocarditis. In addition, aortic insufficiency was progressed because of nonbacterial thrombotic endocarditis on the ventricular side, in areas of high turbulence around the heart valve.ConclusionsOur case is unusual given the unicuspid aortic valve concomitant with aortic insufficiency, which was presumably independent of underlying infectious endocarditis because of the location of the vegetation and the lack of evidence of valve destruction. Therefore, attention should be paid to a variety of complications in the setting of unicuspid aortic valve.

Patient: Female, 21-month-oldFinal Diagnosis: Mumps myocarditisSymptoms: Fever • left ear painMedication: —Clinical Procedure: Not applicableSpecialty: Pediatrics and NeonatologyObjective:Rare co-existance of disease or pathologyBackground:Myocarditis is a rare but potentially fatal complication of mumps virus infection. Left ventricular non-compaction (LVNC) is a rare congenital abnormality that can lead to development of low cardiac output, cardiac dys-function, arrhythmias, or sudden cardiac death. To the best of our knowledge, no autopsy cases of mumps myocarditis with LVNC have been reported in the literature. Here, we report an autopsy case of a 21-month-old girl who died due to mumps myocarditis associated with an undiagnosed LVNC.Case Report:Postmortem computed tomography demonstrated bilaterally enlarged parotid glands. Serum analysis of anti-mumps IgM titer was positive. Macroscopic and histological examinations revealed glandular destruction with massive inflammatory cell infiltration of the enlarged parotid glands and mild inflammatory cell infiltration of the heart, which showed prominent trabeculations and deep intra-trabecular recesses, indicating LVNC. Immunohistochemical analyses showed positive immunostainings for mumps in the cardiac and salivary gland tissues.Conclusions:These findings suggest that mumps myocarditis associated with LVNC contributed to this patient’s death. Myocarditis patients with other comorbidities, including LVNC, may be at higher risk of sudden death. Further reports of mumps myocarditis and LVNC are needed to better understand the mechanisms of sudden unexpected deaths in children.

Unicuspid aortic valve is a rare congenital cardiac abnormality, leading to aortic stenosis or regurgitation. We report the case of a 55-year-old man with severe aortic regurgitation caused by a unicuspid valve mimicking quadricuspid valve.

Two rare cases of congenital aortic stenosis showing a discrepancy between preoperative imaging diagnosis, intraoperative findings, and histopathological diagnosis

Left ventricular hypertrophy (LVH) is a well-recognized cardiac dysfunction in infants of mothers with gestational diabetes mellitus (GDM). Left ventricular noncompaction (LVNC) is a cardiomyopathy that is morphologically characterized by numerous prominent trabeculations and deep intertrabecular recesses on cardiovascular imaging. However, there have been no case reports on neonates of mothers with GDM showing LVH and LVNC. A patient, with LVH of a mother with GDM, was delivered at 36 weeks of gestation. Prominent trabeculations in the LV, suggesting LVNC, instead of LVH, were apparent 1 week after birth. A heterozygous deletion variant in the MYH7 gene (NM_000257.4: c.1090T>C, p.Phe364Leu) was discovered through genetic testing using a cardiomyopathy-associated gene panel in the patient and his father and the older brother who had LVNC. The patient is now 5 years old and does not have major cardiac events, although LVNC persisted. This is the first case of LVH secondary to a mother with GDM and LVNC with a novel variant in the MYH7 gene. Genetic testing should be conducted to obtain an accurate outcome and medical care in a patient with LVH and subsequently prominent hypertrabeculation in the LV.