Genotype-positive, phenotype-negative carriers of an MYBPC3 mutation demonstrated significantly decreased myocardial external efficiency compared to healthy relatives (27% vs 36%, P=0.02).
Observational (n=26)
Does the presence of an MYBPC3 mutation alter myocardial efficiency, perfusion, or energetics in phenotype-negative carriers compared to healthy relatives?
Absolute Event Rate: 27% vs 36%
p-value: p=0.02
AIMS: Next to left ventricular (LV) hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by microvascular dysfunction and reduced myocardial external efficiency (MEE). Insights into the presence of these abnormalities as early markers of disease are of clinical importance in risk stratification, and development of therapeutic approaches. Therefore, the aim was to investigate myocardial perfusion and energetics in genotype-positive, phenotype-negative HCM subjects (carriers). METHODS AND RESULTS: Fifteen carriers of an MYBPC3 mutation underwent (15)Owater positron emission tomography (PET) to assess myocardial blood flow (MBF). (11)Cacetate PET was performed to obtain myocardial oxygen consumption (MVO(2)). By use of cardiovascular magnetic resonance imaging, LV volumes and mass were defined to calculate MEE, i.e. the ratio between external work and MVO(2). Eleven healthy, genotype-negative, family relatives underwent similar scanning protocols to serve as a control group. Left ventricular mass was comparable between carriers and controls (93 ± 25 vs. 99 ± 21 g, P= 0.85), as was MBF at rest (1.19 ± 0.34 vs. 1.18 ± 0.32 mL min(-1) g(-1), P= 0.92), and during hyperaemia (3.87 ± 0.75 vs. 3.96 ± 0.86 mL min(-1) g(-1), P= 0.77). Myocardial oxygen consumption averaged 0.137 ± 0.057 mL min(-1) g(-1) in carriers and was not significantly different from controls (0.125 ± 0.043 mL min(-1) g(-1), P= 0.29). Cardiac work, however, was slightly reduced in carriers (7398 ± 1384 vs. 9139 ± 2484 mmHg mL in controls, P= 0.08). As a consequence, MEE was significantly decreased in carriers (27 ± 10 vs. 36 ± 8% in controls, P= 0.02). CONCLUSION: Carriers display reduced myocardial work generation in relation to oxygen consumption, in the absence of hypertrophy and flow abnormalities. Hence, impaired myocardial energetics may constitute a primary component of HCM pathogenesis.
Timmer et al.（金曜日）は、肥大型心筋症における観察研究を実施しました（n=26）。MYBPC3変異キャリアの状態と健康な、遺伝子型陰性の家族親族が心筋外効率（MEE）について評価されました（p=0.02）。遺伝子型陽性、表現型陰性のMYBPC3変異キャリアは、健康な親族と比較して心筋外効率が有意に低下していることが示されました（27% vs 36%、P=0.02）。