Enhancing risk prediction for sudden cardiac death: quantitative late gadolinium enhancement analysis in hypertrophic cardiomyopathy

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Hypertrophic cardiomyopathy (n=617). Intervention: Dual-threshold gray zone late gadolinium enhancement (LGE) extent vs. Single-threshold LGE extent / Lower LGE extent. Primary outcome: Sudden cardiac death (SCD) or aborted SCD (HR 1.220, 95% CI 1.085-1.372, p=<0.001).

Q: What does this research mean for the field?

Dual-threshold gray zone LGE quantification independently predicts sudden cardiac death in hypertrophic cardiomyopathy with a stronger association than single-threshold methods, providing incremental prognostic value beyond standard clinical risk models. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

L L Wang; Hongbo Zhang; Guanyu Lu; Junjie Zhou; Zhihui Lu; Lanling Wang; Chen Zhang; Xiaohai Ma; Shuang Li; Lei Zhao

doi:10.1186/s13244-026-02385-3

August 26, 2026Insights into ImagingOpen Access

Enhancing risk prediction for sudden cardiac death: quantitative late gadolinium enhancement analysis in hypertrophic cardiomyopathy

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Key result

Dual-threshold gray zone LGE quantification (2 SD - 3 SD) independently predicted sudden cardiac death in hypertrophic cardiomyopathy with a stronger association (HR 1.220) than single-threshold methods.

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Why the study?

The optimal late gadolinium enhancement quantification approach for sudden cardiac death risk stratification in hypertrophic cardiomyopathy remains uncertain.

Does dual-threshold gray zone LGE quantification improve sudden cardiac death risk prediction compared to single-threshold methods and standard clinical models in patients with hypertrophic cardiomyopathy?

Key Points

To assess the prognostic value of multiple late gadolinium enhancement (LGE) quantification methods for predicting sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM).
Consecutively enrolled 617 HCM patients who underwent cardiac magnetic resonance (CMR) examinations at a single center, with a mean follow-up of 67.9 ± 21.0 months.
Quantified LGE using single-threshold n-standard deviation (SD) methods (2–6 SDs), the full width at half maximum method, and dual-threshold gray-zone techniques.
The primary endpoint of SCD or aborted SCD occurred in 24 patients (3.9%), including 12 SCD events and 12 aborted SCD events.
All dual-threshold gray-zone measures and five single-threshold LGE quantifications (2–6 SDs) independently predicted SCD (adjusted HR range: 1.031–1.220, all adjusted p < 0.05), with gray zone exhibiting stronger associations (HR range: 1.091–1.220) than single-threshold metrics (HR range: 1.031–1.046).
Both single- and dual-threshold quantification improved discrimination over the composite AHA/ACC model, yielding net reclassification improvements of 0.321 and 0.397 and C-statistics of 0.794–0.871 versus 0.794–0.898 (p = 0.155).

Study Design

Type

Cohort (n=617)

Multicenter

No

Structured PICO

Does dual-threshold gray zone LGE quantification improve sudden cardiac death risk prediction compared to single-threshold methods and standard clinical models in patients with hypertrophic cardiomyopathy?

P

Population

617 adult patients with hypertrophic cardiomyopathy who underwent cardiac magnetic resonance imaging, followed for a mean of 67.9 months to assess sudden cardiac death risk.

E

Exposure

Late gadolinium enhancement (LGE) quantification using dual-threshold 'gray zone' methods (e.g., 2 SD-3 SD, 2 SD-4 SD) and single-threshold n-SD techniques (2-6 SDs) on CMR.

C

Comparator

Comparison between different LGE quantification methods (single-threshold vs. dual-threshold gray zone) and evaluation of incremental value over the standard composite AHA/ACC clinical risk model.

O

Outcome

Composite of sudden cardiac death (SCD) or aborted SCD (appropriate ICD shock for ventricular arrhythmia, episode of ventricular fibrillation, or spontaneous sustained ventricular tachycardia causing hemodynamic instability and requiring cardioversion) at mean 67.9 months follow-up.hard clinical

Main Result

Hazard Ratio: 1.22 (95% CI 1.085–1.372)

p-value: p=<0.001

Limitations

Retrospective, single-center design at a tertiary referral institution may have introduced referral bias
LV maximal outflow tract gradient was unavailable, so the ESC Risk-SCD score could not be calculated
LGE quantification was performed using two-dimensional, breath-hold imaging with relatively thick slices (6–8 mm)
Differences in contrast agent type and dosing may have influenced LGE quantification
Low incidence of SCD events may limit statistical power
Direct histological validation of the mechanism in HCM is challenging as correlating LGE with myocardial pathology requires matching imaging to post-mortem tissue
Single-center retrospective design

Implication

Dual-threshold gray-zone LGE quantification on CMR provides stronger prognostic value for sudden cardiac death in HCM than conventional single-threshold methods, offering incremental value over standard AHA/ACC risk models.

Abstract

Objectives To assess the prognostic value of multiple late gadolinium enhancement (LGE) quantification methods for sudden cardiac death (SCD) prediction in hypertrophic cardiomyopathy (HCM). Materials and methods In this single-center retrospective study, 617 HCM patients who underwent cardiac magnetic resonance (CMR) examinations were consecutively enrolled. LGE was quantified using the n -standard deviation (SD) technique (with multiple thresholds) and the full width at half maximum method. “Gray zone” was defined as the myocardium with signal intensity between two predefined thresholds on LGE images. The primary outcome was SCD or aborted SCD. Results Among 617 HCM patients, 424 (68.7%) were male, mean age was 49.1 ± 14.0 years, and LGE was identified in 438 (71.0%). During 67.9 ± 21.0 months of follow-up, 24 patients (3.9%) reached the primary endpoint. All dual-threshold gray zone measures and five single-threshold LGE quantifications (2–6 SDs) independently predicted SCD (HR range: 1.031–1.220, all adjusted p < 0.05). Gray zone (HR range: 1.091–1.220) showed stronger associations than single-threshold LGE measures (HR range: 1.031–1.046). Both approaches improved discrimination beyond the composite American Heart Association (AHA)/American College of Cardiology (ACC) model, with increased net reclassification improvement (0.321 and 0.397, respectively) and comparable C-statistics (0.794–0.871 vs 0.794–0.898, p = 0.155). Conclusion While conventional single-threshold LGE quantification predicts SCD in HCM, dual-threshold gray-zone analysis demonstrates stronger associations. Both approaches provide incremental prognostic value beyond the AHA/ACC guideline-based risk model. These findings underscore the importance of standardizing LGE quantification to improve SCD risk stratification in patients with HCM. Key Points Question: The optimal LGE quantification approach for SCD risk stratification in HCM remains uncertain. Findings: Both single- and dual-threshold LGE quantification independently predict SCD in patients with HCM, while dual-threshold gray zone metrics demonstrate stronger prognostic associations. Critical Relevance: By systematically comparing multiple LGE quantification approaches, this study highlights the impact of methodological variability on SCD risk stratification in HCM, underscores the need for standardized LGE assessment, and informs clinical radiology practice.

Discussion

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Cite This Study

Wang et al. (2026) conducted a cohort in Hypertrophic cardiomyopathy (n=617). Dual-threshold gray zone late gadolinium enhancement (LGE) extent vs. Single-threshold LGE extent / Lower LGE extent was evaluated on Sudden cardiac death (SCD) or aborted SCD (HR 1.220, 95% CI 1.085-1.372, p=<0.001). Dual-threshold gray zone LGE quantification (2 SD - 3 SD) independently predicted sudden cardiac death in hypertrophic cardiomyopathy with a stronger association (HR 1.220) than single-threshold methods.

synapsesocial.com/papers/6a916ea0d15324a1df3aa6ed https://doi.org/10.1186/s13244-026-02385-3

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Enhancing risk prediction for sudden cardiac death: quantitative late gadolinium enhancement analysis in hypertrophic cardiomyopathy

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Enhancing risk prediction for sudden cardiac death: quantitative late gadolinium enhancement analysis in hypertrophic cardiomyopathy

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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