Lowering the Recommended Maximal Wall Thickness Threshold Improves Diagnostic Sensitivity in Asians With Hypertrophic Cardiomyopathy

Thu-Thao Le; Benjamin Huang; Chee Jian Pua; Vineet Tornekar; Annette Schumacher-Maurer; Desiree-Faye Toh; Jennifer Bryant; Briana Ang; Ben Corden; Sanjay K Prasad; Hak-Chiaw Tang; Stuart A Cook; Calvin W L Chin

doi:10.1016/j.jacasi.2021.07.001

Lowering the Recommended Maximal Wall Thickness Threshold Improves Diagnostic Sensitivity in Asians With Hypertrophic Cardiomyopathy

JACC Asia. 2021 Sep 21;1(2):218-226. doi: 10.1016/j.jacasi.2021.07.001. eCollection 2021 Sep.

Authors

Thu-Thao Le^{1

2}, Benjamin Huang¹, Chee Jian Pua^{1

3}, Vineet Tornekar¹, Annette Schumacher-Maurer¹, Desiree-Faye Toh¹, Jennifer Bryant¹, Briana Ang¹, Ben Corden^{1

4}, Sanjay K Prasad^{4

5}, Hak-Chiaw Tang^{1

2}, Stuart A Cook^{1

2}, Calvin W L Chin^{1

2}

Affiliations

¹ Department of Cardiology, National Heart Centre Singapore, Singapore.
² Cardiovascular Academic Clinical Program, Duke NUS Medical School, Singapore.
³ Yong Loo Lin School of Medicine, National University Singapore, Singapore.
⁴ National Heart and Lung Institute, Imperial College, London, United Kingdom.
⁵ Royal Brompton Hospital, London, United Kingdom.

Abstract

Background: Hypertrophic cardiomyopathy (HCM) is defined as left ventricular end-diastolic maximal wall thickness (WT_Max) ≥15.0 mm, without accounting for ethnicity, sex, and body size. It is well-established that Asians have smaller hearts than do Caucasians.

Objectives: This study aims to examine the implications of this single absolute WT_Max threshold on the diagnosis of HCM in Asians.

Methods: The study consisted of 360 healthy volunteers (male: n = 174; age: 50 ± 12 years) and 114 genetically characterized patients with HCM (male: n = 83; age: 52 ± 13 years; genotype-positive, n = 39). All participants underwent cardiovascular magnetic resonance. WT_Max was measured semiautomatically at end-diastole according to the standard 16 myocardial segments.

Results: Healthy male volunteers had increased WT_Max compared with that of female volunteers (8.4 ± 1.2 mm vs 6.6 ± 1.1 mm, respectively; P < 0.001). Conversely, WT_Max was similar between male and female patients with HCM (15.2 ± 3.4 mm vs 14.7 ± 3.0 mm, respectively; P = 0.484) and between those with and without a pathogenic gene variant (P = 0.828). Using the recommended diagnostic threshold of 15.0 mm, 56 patients with HCM had WT_Max <15.0 mm and no healthy volunteers had WT_Max >15.0 mm (specificity of 100% and sensitivity of 51%). Lowering WT_Max thresholds to 10.0 mm in female patients and 12.0 mm in male patients did not affect specificity (100%) but significantly improved sensitivity (84%). Despite lower left ventricular mass, female patients with HCM demonstrated more features of adverse cardiac remodeling than did male patients: increased myocardial fibrosis, higher asymmetric ratio, and disproportionately worse myocardial strain.

Conclusions: The study highlights cautious application of guideline-recommended WT_Max to diagnose HCM in Asians. Lowering WT_Max to account for ethnicity and sex improves diagnostic sensitivity without compromising specificity.

Keywords: AUC, area under the curve; CMR, cardiovascular magnetic resonance; HCM, hypertrophic cardiomyopathy; LV, left ventricle/left ventricular; LVH, left ventricular hypertrophy; NPV, negative predictive value; PPV, positive predictive value; WTMax, maximal wall thickness; asymmetrical hypertrophy; cardiovascular magnetic resonance; hypertrophic cardiomyopathy; sex-specific diagnostic thresholds.