PMC8821647_01
(A) Transthoracic echocardiography (TTE) showed remarkably asymmetric left ventricular (LV) hypertrophy with 23-mm thickness of the interventricular septum and 10-mm thickness of the posterior wall. (B) Pressure gradient of the left ventricular outflow tract (LVOT) was 44 mmHg after dobutamine infusion at a speed of 45 ug/ml. Follow-up TTE 8 years after CoA correction showed similar LV hypertrophy as before intervention (C) and flow velocity at the descending aorta was 2.9 m/s (D). Cardiac magnetic resonance imaging (MRI) showed asymmetric LV hypertrophy in (E) apical 4 chamber view and (F) short-axis view. (G) Twelve-lead echocardiogram (EKG) showed supraventricular tachycardia with right bundle branch block (RBBB) at a heart rate of 190 bpm. Holter monitor (H,I) revealed non-sustained ventricular tachycardia (black line in H), supraventricular tachycardia with RBBB (black triangle in H), and premature ventricular beats (black line in I).
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Transthoracic echocardiography (TTE) demonstrated asymmetric left ventricular (LV) hypertrophy with abnormal systolic anterior motion (SAM) of the anterior mitral valve leaflet and obstruction of left ventricular outflow tract (LVOT) (Figures 1A,B). Cardiac MRI showed a finding of asymmetric left ventricular hypertrophy as TTE (Figures 1E,F). EKG showed supraventricular tachycardia with RBBB (Figure 1G). Holter monitor results showed frequent premature ventricular beats (Figure 1I), non-sustained ventricular tachycardia and supraventricular tachycardia (Figure 1H) that had the same morphology as the one captured by 12-lead EKG (Figure 1G). Moreover, repeated TTE on 8-year follow-up showed similar HCM-related imaging features as before the stent treatment, such as similarly thickened interventricular septum (Figure 1C), and flow velocity in the descending aorta was around 2.9 m/s (Figure 1D).
CT angiography (CTA) of the aorta (A) showed marked narrowing in the isthmic region of the descending aorta (white block arrow) and patent ductus arteriosus (PDA) (white arrow) connecting the aorta and the pulmonary artery. Dilatation of the innominate artery and the left subclavian artery (white block arrows), and extensive collateral circulation (white arrows) were shown in (B). Follow-up CTA of the aorta 8 years after stent repair showed reduced collateral circulation (C, white arrows), and the PDA is not shown (C, asterisk). Aortic angiography showed remarkable isthmic coarctation of the aorta with dilated innominate artery and left subclavian artery (D) and exuberant collateral circulation (E). Pressure gradient between the proximal and distal ends to the aortic obstruction was 74 mmHg (H). The descending aorta, after placement of stent, was shown (F) with equalization of pressure at the proximal and distal ends of the descending aorta (I). Repeated aortic angiography at 8-year follow-up showed patency of the covered stent and reduction in collateral circulation (G), and no pressure gradient was found, 177/90 mmHg at the proximal vs. 174/92 mmHg at the distal end of descending aorta, respectively (J).
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The descending aorta was remarkably narrowed at the isthmus by approximately 2 cm past the left subclavian artery (Figures 2A,B). The innominate artery and the left subclavian artery were dilated with extensive collateral circulation arising from those arteries (Figure 2B). A small vessel, immediately distal to the aortic obstruction, was found to be connecting the descending aorta and the pulmonary artery (Figure 2A), confirming the presence of PDA. Angiography of the root of the aorta showed narrowing of the aortic isthmus (Figure 2D) and marked collateral circulation (Figure 2E). Pressure was 200/100 mmHg at the proximal end of the descending aorta to the obstruction and 124/90 mmHg at the distal end to the obstruction (Figure 2H). After balloon dilatation, the covered endovascular stent was placed at the aortic isthmus, and PDA was blocked by the stent concomitantly (Figure 2F). Aortic pressures were equalized at the proximal and distal ends of the descending aorta (Figure 2I). On 8-year follow-up, aortic CTA and angiography were repeated, which showed patency of the covered stent (Figures 2C,G), and no pressure gradient was detected at the proximal and distal ends of the descending aorta (Figure 2J). Pressure was 177/90 mmHg at the proximal end and 174/92 mmHg at the distal end of the descending aorta, respectively (Figure 2J). Aortic CTA showed reduced collateral circulation and disappearance of PDA compared to before the stent treatment (Figure 2C).
Results of sequencing quality and mutation identification. Two likely novel heterozygous hypertrophic cardiomyopathy (HCM)-causing mutations were identified, DSP (p.Val520Met, c.1558G>A) (SIFT = 0.05; PolyPhen-2 = 1) and MYBPC3 (p.Tyr525Ser, c.1574A>C) (SIFT = 0; PolyPhen-2 = 0.976).
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ESP database, nonpathogenic variants in the ClinVar database, and in silico functional predicting, we identified two likely novel heterozygous HCM-causing mutations, DSP (p.Val520Met, c.1558G>A) (SIFT = 0.05; PolyPhen-2 = 1) and MYBPC3 (p.Tyr525Ser, c.1574A>C) (SIFT = 0; PolyPhen-2 = 0.976) (Figure 3) according to the guideline. Except for these mutations, we detected no other likely pathogenic mutation in all cardiomyopathy-related genes.