Carriers of the hypertrophic cardiomyopathy MYBPC3 mutation are characterized by reduced myocardial efficiency in the absence of hypertrophy and microvascular dysfunction.
OBJECTIVE
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).


RESULTS
Fifteen carriers of an MYBPC3 mutation underwent [(15)O]water positron emission tomography (PET) to assess myocardial blood flow (MBF). [(11)C]acetate 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).


CONCLUSIONS
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.
Department of Cardiology, VU University Medical Center, De Boelelaan 1117, Amsterdam, The Netherlands.
Stefan A J
SA
Timmer
Tjeerd
T
Germans
Wessel P
WP
Brouwer
Mark
M
Lubberink
Jolanda
J
van der Velden
Arthur A M
AA
Wilde
Imke
I
Christiaans
Adriaan A
AA
Lammertsma
Paul
P
Knaapen
Albert C
AC
van Rossum
D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology*; D004247:DNA / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D055806:Microvessels / Q000503:physiopathology*; D008875:Middle Aged; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D009218:Myosins; D010101:Oxygen Consumption; D049268:Positron-Emission Tomography; D011379:Prognosis; D012039:Regional Blood Flow; D016277:Ventricular Function, Left / Q000502:physiology*; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D004247:DNA; D009218:Myosins; D000099163:Myosin Binding Protein C