TOPLINE: 

Wall thickness standard deviation (WTSD), a measure of heart wall heterogeneity, identified more than 90% of patients with hypertrophic cardiomyopathy (HCM) and 64% of sarcomere mutation carriers without overt hypertrophy, outperforming conventional wall thickness thresholds, according to a prospective study.

METHODOLOGY:

• Researchers conducted a multicentre cardiac magnetic resonance (CMR) study in Italy, including 382 healthy control individuals (mean age, 51 years; 216 men), 297 patients with guideline-based HCM diagnosis, 82 sarcomere mutation carriers without overt hypertrophy, and 180 patients with other cardiac conditions (75 and 105 without left ventricular hypertrophy).
• End-diastolic wall thickness was measured in 16 myocardial segments using CMR, and WTSD was computed for each individual to quantify wall thickness heterogeneity across the left ventricle.
• Age- and sex-specific normality thresholds for WTSD were derived from healthy control individuals, and their diagnostic performance was compared with that of demographic-based personalised thresholds and body surface area-indexed maximal wall thickness.
• The primary outcome was the diagnostic performance of WTSD for identifying patients with HCM and mutation carriers vs control individuals and those with other cardiac conditions.

TAKEAWAY:

• WTSD was significantly higher in patients with HCM (4.3 ± 1.1 mm) and mutation carriers (2.3 ± 0.3 mm) than in healthy control individuals (1.3 ± 0.3; P < .0001 for both), and it significantly distinguished HCM from other hypertrophic conditions, with an area under the curve (AUC) of 0.79.
• WTSD demonstrated superior diagnostic performance for HCM, with high sensitivity (97%), specificity (99%), and AUC (0.98), significantly outperforming demographic-based personalised thresholds (AUC, 0.91; P < .0001) in identifying patients vs control individuals.
• For mutation carriers without overt hypertrophy, WTSD achieved an AUC of 0.82, with a sensitivity of 64% and specificity of 99%. WTSD also significantly distinguished sarcomere mutation carriers from individuals with other nonhypertrophic conditions (AUC, 0.81), demonstrating diagnostic performance significantly superior to that of conventional thresholds.
• WTSD identified 91 of 92 women with HCM, with a sensitivity of 98.9%, specificity of 100%, and an AUC of 0.995, showing diagnostic performance significantly superior to that of other parameters (P < .0001 for most comparisons). Among 54 mutation carriers, WTSD identified 40 individuals, with a sensitivity of 74.0%, specificity of 99.0%, and an AUC of 0.87, significantly outperforming all other wall thickness parameters (P < .0001 for all comparisons).

IN PRACTICE:

"These findings, if confirmed by future large population study, may support the integration of WTSD into diagnostic algorithms, promoting a shift from rigid threshold-based definitions toward a more dynamic, sex-based, and sensitive approach to HCM diagnosis and risk stratification," the authors wrote.

SOURCE:

The study was led by Giovanni Donato Aquaro, MD, University of Pisa, Pisa, Italy; Roberto Licordari, MD, PhD, University of Messina, Messina, Italy; and Giancarlo Todiere, MD, PhD, Fondazione Toscana G. Monasterio, Pisa, Italy. It was published online on April 02, 2026, in European Heart Journal-Cardiovascular Imaging.

LIMITATIONS:

The study included a relatively small cohort with few mutation carriers, limiting generalisability. Included individuals were almost exclusively Caucasian and recruited from Italian centres; therefore, the proposed WTSD thresholds might not have been applicable to other ethnic groups. Patients with borderline wall thickness were not specifically enrolled, and the study was underpowered to detect gene-specific WTSD differences for rarer sarcomeric genes despite comprehensive panel testing. Data on drug histories in mutation carriers were not collected prospectively, and the study could not assess whether WTSD distinguished HCM from physiological hypertrophy in elite athletes.

DISCLOSURES:

The study was funded by institutional funds from the G. Monasterio CNR-Tuscany Foundation, Pisa, Italy, and the University of Pisa. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.