Integrating Genotyping and Left Atrial Strain Analysis Enhances Risk Stratification in Hypertrophic Cardiomyopathy

Q: What are the key findings of this study?

Sarcomere-positive genotype with reduced left atrial reservoir strain markedly increased progression to LV systolic dysfunction in HCM (sHR 8.31, 95% CI 2.25-30.7; P=0.001).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Hypertrophic cardiomyopathy (HCM) with preserved LVEF (≥50%) (n=101). Intervention: Sarcomere-positive genotype combined with reduced left atrial reservoir strain (LARS <22.2%) vs. Remaining HCM cohort (sarcomere-negative or preserved LARS ≥22.2%). Primary outcome: Progression to left ventricular systolic dysfunction (LVSD, defined as LVEF <50%) (sHR 8.31, 95% CI 2.25-30.7, p=0.001).

Q: What does this research mean for the field?

A sarcomere-positive genotype combined with reduced left atrial reservoir strain is associated with a markedly increased risk of progression to left ventricular systolic dysfunction in patients with hypertrophic cardiomyopathy. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Takashi Hiruma; Koki Nakanishi; Shunsuke Inoue; Seitaro Nomura; Yuriko Yoshida; Zhehao Dai; Ryo Abe; Takanobu Yamada; Kanna Fujita; Manami Katoh; Toshiyuki Ko; Masamichi Ito; Junichi Ishida; Eisuke Amiya; Masaru Hatano; Norifumi Takeda; Hiroyuki Morita; Norihiko Takeda; Issei Komuro

doi:10.1016/j.jacadv.2026.102863

Key result

Sarcomeric HCM with reduced LA reservoir strain linked to ~8.3-fold higher risk of LV systolic dysfunction.

sHR 8.31
95% CI 2.25-30.7
P=0.001
n=101

Figures

Graphical abstract published by JACC Advances — Graphical abstract · Published by JACC Advances · CC BY

Why the study?

Does integrating genotyping and speckle-tracking echocardiography left atrial strain analysis improve risk stratification for progression to left ventricular systolic dysfunction in patients with hypertrophic cardiomyopathy?

Key Points

To investigate whether myocardial strain parameters predict progression to left ventricular systolic dysfunction in genotyped patients with hypertrophic cardiomyopathy.
Evaluated N=101 genotyped patients with hypertrophic cardiomyopathy (23.8% sarcomere positive) followed for a median of 5.0 (IQR: 2.4-8.7) years.
Measured left ventricular global longitudinal strain (LVGLS) and left atrial reservoir strain (LARS) using speckle-tracking echocardiography.
Tracked the primary endpoint of progression to left ventricular systolic dysfunction (ejection fraction <50%) and a secondary composite endpoint of systolic dysfunction, heart-failure hospitalization, and death.
Sarcomere-positive patients with low LARS exhibited a markedly higher rate of progression to systolic dysfunction compared to other patients (sHR: 8.31; 95% CI: 2.25-30.7; P = 0.001; 5-year incidence 31.4% vs 5.7%).
The combination of sarcomere positivity and low LARS also predicted the secondary composite clinical endpoint (HR: 4.76; 95% CI: 1.59-14.2; P = 0.005).

Study Design

Type

Cohort (n=101)

Blinding

Blinded outcome assessment (physicians and staff collecting clinical data and observers performing strain analysis were blinded to genetic results)

Multicenter

No

Structured PICO

Does integrating genotyping and speckle-tracking echocardiography left atrial strain analysis improve risk stratification for progression to left ventricular systolic dysfunction in patients with hypertrophic cardiomyopathy?

P

Population

101 genotyped patients in Japan with hypertrophic cardiomyopathy and preserved LVEF (median age 62 years, 46.5% female, 23.8% sarcomere-positive), free of prior septal reduction therapy or storage diseases, followed for a median of 5.0 years.

E

Exposure

Genotyping (target sequencing of 83 genes or whole exome sequencing to identify pathogenic/likely pathogenic variants in 9 major sarcomere-encoding genes) combined with speckle-tracking echocardiography myocardial strain analysis (measuring left ventricular global longitudinal strain [LVGLS], left atrial reservoir strain [LARS], LA pump strain, and LA conduit strain).

C

Comparator

Comparison across genotypes (sarcomere-positive [n=24] vs sarcomere-negative [n=77]) and left atrial reservoir strain levels (high vs low divided by the median value of 22.2%).

O

Outcome

Progression to left ventricular systolic dysfunction (LVSD, defined as LVEF <50%) during follow-up (median 5.0 years, IQR: 2.4-8.7 years), analyzed with all-cause death as a competing event.surrogate

Main Result

Hazard Ratio: 8.31 (95% CI 2.25–30.7)

Absolute Event Rate: 31.4% vs 5.7%

p-value: p=0.001

Limitations

Single-center, retrospective study conducted at a tertiary referral hospital, limiting generalizability
Small sample size and low number of primary endpoint events (n=8), limiting statistical power, preventing multivariable adjustment, and yielding wide confidence intervals
Temporal relationship between LARS decline and LV systolic deterioration was inferred from baseline data rather than serial longitudinal imaging
Lack of certain prognostic biomarker data (e.g., cardiac troponin levels in all patients) to assess incremental prognostic value
Lack of cardiac magnetic resonance imaging data to evaluate the relationship between strain parameters and myocardial fibrosis
Use of cohort median-based dichotomization for LARS rather than established external cutoff values
Retrospective single-center study design
Limited number of study endpoints permitting only univariate regression analyses
No patients received cardiac myosin inhibitors as they were not approved in Japan during the study period

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

In patients with hypertrophic cardiomyopathy and preserved ejection fraction, reduced left atrial reservoir strain—unlike left ventricular global longitudinal strain—is independently associated with progression to left ventricular systolic dysfunction, and combining it with sarcomere genotyping identifies a very high-risk subpopulation.

Abstract

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) who progress to left ventricular systolic dysfunction (LVSD) are at an increased risk of lethal arrhythmias and end-stage heart failure. Early identification of this high-risk subpopulation is crucial; however, current risk stratification remains insufficient. OBJECTIVES: The objective of the study was to investigate the association of myocardial strain parameters with progression to LVSD in genotyped HCM patients. METHODS: Sarcomere positive was defined as harboring pathogenic or likely pathogenic variants in sarcomere-encoding genes. Speckle-tracking echocardiography was used to measure left ventricular global longitudinal strain (LVGLS) and left atrial reservoir strain (LARS). The primary endpoint was progression to LVSD (ejection fraction <50%) and the secondary endpoint was a composite of progression to LVSD, heart-failure hospitalization, and all-cause death. RESULTS: A total of 101 patients (23.8% sarcomere positive) were included and followed up for 5.0 (IQR: 2.4-8.7) years. No significant association was observed between genotype and strain parameters. Sarcomere positive (subdistribution HR [sHR]: 5.07; 95% CI: 1.25 to 20.6; P = 0.023) and lower LARS (sHR: 1.10 per 1% decrease; 95% CI: 1.02-1.18; P = 0.015), but not LVGLS, were significantly associated with the primary endpoint. Sarcomere-positive patients with reduced LARS faced markedly elevated incidence for the primary endpoint (sHR: 8.31; 95% CI: 2.25-30.7; P = 0.001). Consistent findings were observed in terms of the secondary endpoint (HR: 4.76; 95% CI: 1.59-14.2; P = 0.005). CONCLUSIONS: LARS was associated with progression to LVSD in HCM, potentially reflecting the preclinical stage of LVSD, whereas LVGLS was not. In this exploratory study, integrating left atrial strain analysis with genotyping may have potential value in risk stratification, with implication for early detection of vulnerable individuals.

Discussion

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Cite This Study

Hiruma et al. (2026) conducted a cohort in Hypertrophic cardiomyopathy (HCM) with preserved LVEF (≥50%) (n=101). Sarcomere-positive genotype combined with reduced left atrial reservoir strain (LARS <22.2%) vs. Remaining HCM cohort (sarcomere-negative or preserved LARS ≥22.2%) was evaluated on Progression to left ventricular systolic dysfunction (LVSD, defined as LVEF <50%) (sHR 8.31, 95% CI 2.25-30.7, p=0.001). Sarcomere-positive genotype with reduced left atrial reservoir strain markedly increased progression to LV systolic dysfunction in HCM (sHR 8.31, 95% CI 2.25-30.7; P=0.001).

synapsesocial.com/papers/6a3c230ed15afadd906f9c72 https://doi.org/10.1016/j.jacadv.2026.102863

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Integrating Genotyping and Left Atrial Strain Analysis Enhances Risk Stratification in Hypertrophic Cardiomyopathy

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Integrating Genotyping and Left Atrial Strain Analysis Enhances Risk Stratification in Hypertrophic Cardiomyopathy

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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