Key result
Higher LV sphericity index linked to ~47% greater cardiomyopathy risk per SD.
Why the study?
The human heart possesses significant uncharacterized phenotypic variation beyond traditional metrics of size and function, and examining variation in cardiac shape may improve understanding of cardiovascular risk and pathophysiology.
Does increased left ventricular sphericity index predict the incidence of cardiomyopathy and atrial fibrillation in subjects with normal left ventricular size and systolic function?
Observational (n=38,897)
Does increased left ventricular sphericity index predict the incidence of cardiomyopathy and atrial fibrillation in subjects with normal left ventricular size and systolic function?
Effect estimate: HR 1.47 (95% CI 1.10-1.98)
p-value: p=0.01
Increased left ventricular sphericity in structurally normal hearts is an independent predictor of incident cardiomyopathy and atrial fibrillation.
Should not yet guide screening in normal hearts; leaves open incremental value for cardiomyopathy prediction.
BACKGROUND: Quantification of chamber size and systolic function is a fundamental component of cardiac imaging. However, the human heart is a complex structure with significant uncharacterized phenotypic variation beyond traditional metrics of size and function. Examining variation in cardiac shape can add to our ability to understand cardiovascular risk and pathophysiology. METHODS: We measured the left ventricle (LV) sphericity index (short axis length/long axis length) using deep learning-enabled image segmentation of cardiac magnetic resonance imaging data from the UK Biobank. Subjects with abnormal LV size or systolic function were excluded. The relationship between LV sphericity and cardiomyopathy was assessed using Cox analyses, genome-wide association studies, and two-sample Mendelian randomization. FINDINGS: In a cohort of 38,897 subjects, we show that a one standard deviation increase in sphericity index is associated with a 47% increased incidence of cardiomyopathy (hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.10-1.98, p = 0.01) and a 20% increased incidence of atrial fibrillation (HR: 1.20, 95% CI: 1.11-1.28, p < 0.001), independent of clinical factors and traditional magnetic resonance imaging (MRI) measurements. We identify four loci associated with sphericity at genome-wide significance, and Mendelian randomization supports non-ischemic cardiomyopathy as causal for LV sphericity. CONCLUSIONS: Variation in LV sphericity in otherwise normal hearts predicts risk for cardiomyopathy and related outcomes and is caused by non-ischemic cardiomyopathy. FUNDING: This study was supported by grants K99-HL157421 (D.O.) and KL2TR003143 (S.L.C.) from the National Institutes of Health.
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Vukadinovic et al. (2023) conducted an observational in Normal LV size and systolic function (n=38,897). Left ventricle sphericity index was evaluated on Incidence of cardiomyopathy (HR 1.47, 95% CI 1.10-1.98, p=0.01). A one standard deviation increase in left ventricle sphericity index was associated with a 47% increased incidence of cardiomyopathy (HR 1.47; 95% CI 1.10-1.98; P=0.01).
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