Revealing Imbalanced Oxygen Metabolism in Hypertrophic Cardiomyopathy Using a Non-Contrast, Free-Running T2-Based Coronary Sinus Oximetry within Three Minutes

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder and is associated with progressive heart failure, atrial fibrillation, and sudden cardiac death. Hypertrophic remodeling increases myocardial oxygen demand while impairing microvascular supply, making oxygen metabolism central to HCM pathophysiology. Early detection of metabolic imbalance is especially important with the advent of myosin inhibitor therapies (e.g., mavacamten)[1], which can delay surgery and improve outcomes but carry risks of excessive relaxation and adverse events. Despite this need, noninvasive tools for precise phenotyping, staging, and therapy monitoring remain limited. We evaluated a novel free-running coronary sinus (CS) oximetry sequence[2] for rapid, contrast-free quantification of myocardial oxygen extraction fraction (mOEF) in HCM patients.

Methods: Fourteen subjects were prospectively enrolled with institutional approval: 8 HCM patients (meeting diagnostic criteria of maximal LV wall thickness ≥15 mm, or ≥13 mm with gene variant or family history; 6 male, age 55.5±17.7 years) and 6 age- and sex-matched healthy controls (5 male, age 48.5±12.7 years). Imaging was performed at 1.5T (Siemens Aera). Cine CMR was used to assess LV morphology and function. A free-running, T2-based sequence with whole-heart coverage was acquired to measure CS venous oxygenation in under 3 minutes, without contrast or breath-holding. Arterial oxygen saturation (SaO₂) was recorded by pulse oximetry, and mOEF was calculated as (SaO₂ – ScsO₂)/SaO₂.

Results: All subjects completed imaging with high feasibility and excellent image quality. HCM patients showed significantly increased LV mass index (92.0 ± 29.3 g/m² vs. 47.1 ± 11.3 g/m², P< 0.01). CS oxygen saturation was reduced in HCM but did not reach statistical significance (39.8 ± 3.9% vs. 43.5 ± 3.3%, P=0.08). Importantly, mOEF was significantly elevated in HCM (60.0 ± 3.8% vs. 55.3 ± 3.6%, P< 0.05), reflecting greater myocardial oxygen extraction and heightened metabolic demand.

Conclusion: This study demonstrates the feasibility of rapid, non-contrast CS oximetry for detecting myocardial oxygen imbalance in HCM. By providing quantitative metabolic assessment in < 3 minutes, this technique extends beyond structural imaging to enable early detection, staging, and therapy monitoring. Beyond HCM, ongoing studies are applying this framework to a broad spectrum of cardiovascular diseases, including aortic stenosis, ischemic heart disease, and heart failure phenotypes, underscoring its potential as a versatile biomarker of myocardial oxygen metabolism.

Figure 1. Study design and free-running CMR oximetry framework. (A) Study design: patients with hypertrophic cardiomyopathy and age- and sex-matched healthy controls were recruited based on standard clinical criteria. Each subject underwent free-running CMR oximetry along with conventional cine imaging. From the acquired data, LV anatomy, coronary sinus (CS) oxygen saturation (ScsO₂), and myocardial oxygen extraction fraction (mOEF) were derived. (B) Free-running CMR oximetry pipeline: a continuously acquired T₂-prepared inversion recovery (T₂prep-IR) sequence with six inter-echo times (0, 7.5, 15, 22.5, 27.5, and 30 ms) was used for data acquisition. Images were reconstructed with a low-rank tensor (LRT) framework to generate motion-resolved oxygenation-weighted images. A Bloch equation simulation combined with a two-compartment Levenberg–Marquardt model was then applied to derive motion-resolved ScsO₂ maps, enabling quantitative assessment of myocardial oxygenation dynamics.
Figure 2. Coronary sinus oxygenation and myocardial oxygen extraction in HCM. (A) Representative CS ScsO₂ maps from a patient with hypertrophic cardiomyopathy (HCM) and a healthy control. The HCM subject demonstrates markedly reduced CS oxygen saturation. (B) LV mass index derived from cine imaging, illustrating significant hypertrophy in HCM compared with controls. (C–D) Group comparisons of ScsO₂ and myocardial oxygen extraction fraction (mOEF). Although ScsO₂ showed only a trend toward reduction in HCM (P=0.08), this was associated with a significantly elevated mOEF (P <0.05), reflecting increased oxygen extraction and heightened metabolic demand in hypertrophic hearts.