A Unique High-Output Cardiac Hypertrophy Phenotype Arising From Low Systemic Vascular Resistance in Cantu Syndrome.
A Unique High-Output Cardiac Hypertrophy Phenotype Arising From Low Systemic Vascular Resistance in Cantu Syndrome.
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DOI：
10.1161/jaha.122.027363
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发表时间：
2022-12-20
影响因子：
5.4
通讯作者：
Nichols, Colin G.
中科院分区：
文献类型：
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作者：
Singh, Gautam K.;McClenaghan, Conor;Aggarwal, Manish;Gu, Hongjie;Remedi, Maria S.;Grange, Dorothy K.;Nichols, Colin G.
由左心室肥大引起的心脏肥大是发生充血性心力衰竭的危险因素，典型地与收缩和/或舒张心室功能降低相关。较少关注左心室肥大伴心室功能增强和心输出量增加的表型，这可能与高输出量心力衰竭相关。缺乏识别可能会造成诊断模糊和管理复杂性。我们试图系统地描述Cantu综合征（CS）受试者的高输出量心脏肥大，这是由ABCC 9的功能获得变体引起的，ABCC 9编码心血管KATP（ATP敏感性钾）通道亚基。我们纵向研究了31例确诊为ABCC 9变异的CS受试者的心血管表型（中位[四分位距]年龄8岁[3-32岁]，体重指数19.9 [16.5-22.9]，16例男性受试者）。CS受试者表现出显著的左心室肥厚（CS组左心室质量指数86.7 [57.7-103.0] g/m2，n=30;对照组26.6 [24.1-32.8] g/m2，n=17; P<0.0001）和低血压（CS收缩压94.5 [90-103] mmHg，n=17;对照组109 [98-115] mmHg，n=17; P=0.0301; CS舒张压60 [56-66] mmHg，n=17;对照组69 [65-72] mmHg，n=17; P=0.0063）。大多数（21/31）CS受试者表现为左室壁厚度正常的离心性肥厚。在长期随访中，5例年龄>40岁的CS受试者中有4例的充血性心力衰竭症状明显。这些数据定义了CS受试者中由体循环血管阻力降低导致的高输出量心脏肥大的自然史、由体循环血管阻力低导致的高输出量肥大长期后果的定义人群以及进展为高输出量心力衰竭的可能性。
Cardiomegaly caused by left ventricular hypertrophy is a risk factor for development of congestive heart failure, classically associated with decreased systolic and/or diastolic ventricular function. Less attention has been given to the phenotype of left ventricular hypertrophy with enhanced ventricular function and increased cardiac output, which is potentially associated with high‐output heart failure. Lack of recognition may pose diagnostic ambiguity and management complexities. We sought to systematically characterize high‐output cardiac hypertrophy in subjects with Cantu syndrome (CS), caused by gain‐of‐function variants in ABCC9, which encodes cardiovascular KATP (ATP‐sensitive potassium) channel subunits. We studied the cardiovascular phenotype longitudinally in 31 subjects with CS with confirmed ABCC9 variants (median [interquartile range] age 8 years [3–32 years], body mass index 19.9 [16.5–22.9], 16 male subjects). Subjects with CS presented with significant left ventricular hypertrophy (left ventricular mass index 86.7 [57.7–103.0] g/m2 in CS, n=30; 26.6 [24.1–32.8] g/m2 in controls, n=17; P<0.0001) and low blood pressure (systolic 94.5 [90–103] mm Hg in CS, n=17; 109 [98–115] mm Hg in controls, n=17; P=0.0301; diastolic 60 [56–66] mm Hg in CS, n=17; 69 [65–72] mm Hg in control, n=17; P=0.0063). Most (21/31) subjects with CS exhibited eccentric hypertrophy with normal left ventricular wall thickness. Congestive heart failure symptoms were evident in 4 of the 5 subjects with CS aged >40 years on long‐term follow‐up. The data define the natural history of high‐output cardiac hypertrophy resulting from decreased systemic vascular resistance in subjects with CS, a defining population for long‐term consequences of high‐output hypertrophy caused by low systemic vascular resistance, and the potential for progression to high‐output heart failure.