Cardiac "hypertrophy" phenotyping: differentiating aetiologies with increased left ventricular wall thickness on echocardiography

Aaisha Ferkh; Catherina Tjahjadi; Luke Stefani; Paul Geenty; Karen Byth; Kasun De Silva; Anita C Boyd; David Richards; Peter Mollee; Dariusz Korczyk; Mark S Taylor; Fiona Kwok; Eddy Kizana; Arnold C T Ng; Liza Thomas

doi:10.3389/fcvm.2023.1183485

Cardiac "hypertrophy" phenotyping: differentiating aetiologies with increased left ventricular wall thickness on echocardiography

Front Cardiovasc Med. 2023 Jul 3:10:1183485. doi: 10.3389/fcvm.2023.1183485. eCollection 2023.

Authors

Aaisha Ferkh^{1

2}, Catherina Tjahjadi³, Luke Stefani^{1

2}, Paul Geenty^{1

2}, Karen Byth⁴, Kasun De Silva^{1

2}, Anita C Boyd⁵, David Richards⁵, Peter Mollee^{6

7}, Dariusz Korczyk³, Mark S Taylor⁸, Fiona Kwok⁹, Eddy Kizana^{1

2

10}, Arnold C T Ng³, Liza Thomas^{1

2

11}

Affiliations

¹ Westmead Clinical School, University of Sydney, Westmead, NSW, Australia.
² Cardiology Department, Westmead Hospital, Westmead, NSW, Australia.
³ Cardiology Department, Princess Alexandra Hospital, Brisbane, QLD, Australia.
⁴ WSLHD Research and Education Network, Westmead Hospital, Westmead, NSW, Australia.
⁵ Westmead Private Cardiology, Westmead, NSW, Australia.
⁶ Haematology Department, Princess Alexandra Hospital, Brisbane, QLD, Australia.
⁷ School of Medicine, University of Queensland, Brisbane, QLD, Australia.
⁸ Department of Clinical Immunology and Allergy, Westmead Hospital, Westmead, NSW, Australia.
⁹ Haematology Department, Westmead Hospital, Westmead, NSW, Australia.
¹⁰ Centre for Heart Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia.
¹¹ South-West Clinical School, University of New South Wales, Liverpool, NSW, Australia.

Abstract

Aims: Differentiating phenotypes of cardiac "hypertrophy" characterised by increased wall thickness on echocardiography is essential for management and prognostication. Transthoracic echocardiography is the most commonly used screening test for this purpose. We sought to identify echocardiographic markers that distinguish infiltrative and storage disorders that present with increased left ventricular (LV) wall thickness, namely, cardiac amyloidosis (CA) and Anderson-Fabry disease (AFD), from hypertensive heart disease (HHT).

Methods: Patients were retrospectively recruited from Westmead Hospital, Sydney, and Princess Alexandra Hospital, Brisbane. LV structural, systolic, and diastolic function parameters, as well as global (LVGLS) and segmental longitudinal strains, were assessed. Previously reported echocardiographic parameters including relative apical sparing ratio (RAS), LV ejection fraction-to-strain ratio (EFSR), mass-to-strain ratio (MSR) and amyloidosis index (AMYLI) score (relative wall thickness × E/e') were evaluated.

Results: A total of 209 patients {120 CA [58 transthyretin amyloidosis (ATTR) and 62 light-chain (AL) amyloidosis], 31 AFD and 58 HHT patients; mean age 64.1 ± 13.7 years, 75% male} comprised the study cohort. Echocardiographic measurements differed across the three groups, The LV mass index was higher in both CA {median 126.6 [interquartile range (IQR) 106.4-157.9 g/m²]} and AFD [median 134 (IQR 108.8-152.2 g/m²)] vs. HHT [median 92.7 (IQR 79.6-102.3 g/m²), p < 0.05]. LVGLS was lowest in CA [median 12.29 (IQR 10.33-15.56%)] followed by AFD [median 16.92 (IQR 14.14-18.78%)] then HHT [median 18.56 (IQR 17.51-19.97%), p < 0.05]. Diastolic function measurements including average e' and E/e' were most impaired in CA and least impaired in AFD. Indexed left atrial volume was highest in CA. EFSR and MSR differentiated secondary (CA + AFD) from HHT [receiver operating curve-area under the curve (ROC-AUC) of 0.80 and 0.91, respectively]. RAS and AMYLI score differentiated CA from AFD (ROC-AUC of 0.79 and 0.80, respectively). A linear discriminant analysis with stepwise variable selection using linear combinations of LV mass index, average e', LVGLS and basal strain correctly classified 79% of all cases.

Conclusion: Simple echocardiographic parameters differentiate between different "hypertrophic" cardiac phenotypes. These have potential utility as a screening tool to guide further confirmatory testing.

Keywords: Fabry disease; cardiac amyloidosis; cardiac hypertrophy; echocardiography; infiltrative cardiomyopathies; strain imaging.

Grants and funding

AF was supported by the University of Sydney Faculty of Medicine and Health Executive Dean Stipend Scholarship.