Background Myocardial ischaemia is believed to promote fatal life-threatening ventricular arrhythmias in hypertrophic cardiomyopathy (HCM). Oxygen sensitive cardiac magnetic resonance (CMR) or blood oxygen level dependent (BOLD) imaging can detect blunted myocardial oxygenation during vasodilator stress in HCM. Whether or not impairment in stress oxygenation is associated with ventricular arrythmia risk is unknown.

Objectives To investigate the relationship between blunted stress oxygenation and ventricular arrhythmia in HCM and examine the determinants of stress oxygenation in HCM.

Methods 103 genotyped HCM patients and 32 (age, gender and body mass index matched) healthy controls underwent adenosine stress BOLD, stress first pass perfusion imaging and late gadolinium imaging (LGE) to assess stress oxygenation, myocardial perfusion reserve index (MPRI), and fibrosis burden respectively. Stress oxygenation response (BOLD ΔSI) was estimated as a relative increase in oxygen sensitive BOLD signal intensity from rest to peak vasodilator stress. All HCM patients had 24-holter monitoring to assess for ventricular tachycardia (≥3 beats,≥120 beats per minute).

Results As expected, both MPRI (1.5±0.4 v 2.0±0.3, p<0.0001) and stress oxygenation (9.1%±4.1% v 17.0%±1.6%, p<0.0001, figure 1C) were significantly impaired in HCM patients compared to controls. Among HCM patients, twenty six (25%) had ventricular tachycardia and demonstrated more severe impairment in stress oxygenation (6.9%±0.8%) than other patients (9.9%±0.5%, p=0.001). The prevalence of ventricular arrythmia increased with decreasing quartiles of oxygenation (figure 1F). HCM patients in the lowest quartile of stress oxygenation (BOLD ΔSI≤6.5%) were at a three-fold risk of ventricular arrhythmia (OR 3.04, p=0.04) compared to other patients, despite adjusting for differences in LGE mass and other sudden cardiac death risk factors (table 1). Sarcomeric mutation status (β=−2.32, p=0.007) was the only independent predictor of the extent of stress oxygenation after adjusting for univariate confounders (wall thickness, MPRI and LGE mass). Sarcomeric HCM displayed more severe impairment in stress-induced oxygenation than genotype negative HCM and healthy controls (figure 1E).

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Abstract 22 Figure 1

(A) Grey scale rest and stress BOLD image from a healthy control (B) BOLD colour maps demonstrate a relative increase in BOLD SI, from rest (green) to stress (red), by 19.8% in healthy control compared to blunted rise in signal intensity in phenotype negative sarcomeric mutation carrier (Sarc+P- ) (7.6%) and genotype negative HCM (5.6%) (C) Stress myocardial oxygenation is significantly blunted in HCM patients compared to healthy controls (D) Dissociation between MPRI and BOLD ΔSI can be seen in a Sarc+P patient - MPRI 2.2 (normal) versus BOLD ΔSI 7.6% (low) (E) Sarcomeric HCM had the most blunted stress oxygenation amongst all HCM patients (F) Prevalence of ventricular tachycardia rose with decreasing quartiles of myocardial oxygenation. (Error bars represent mean ±standard deviation; ***p<0.0001 comparison with contol; ^##p=0.001 comparison with G-HCM; BOLD SI blood oxygen level dependent imaging signal intensity; MYBPC3 myosin binding protein C 3; MPRI myocardial perfusion reserve index; G-HCM genotype negative HCM; Sarc+Sarcomeric; Sarc+P pre-hypertrophic sarcomeric mutation carriers; VT ventricular tachycardia)

Conclusion In HCM, impaired stress-induced oxygenation is associated with an increased risk of ventricular arrhythmia and may represent a novel biomarker of arrhythmic risk. Sarcomeric mutation status independently predicts a blunted stress oxygenation response in HCM.