Cardiac adrenergic activity is associated with left ventricular hypertrophy in genetically homogeneous subjects with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a genetic disease caused by mutations in genes encoding sarcomeric proteins. However, other genetic and possibly also environmental factors modify the phenotypic expression of left ventricular (LV) hypertrophy. The present study investigated whether cardiac adrenergic activity affects the severity of LV hypertrophy in genetically identical patients with HCM.


METHODS
The study population consisted of 21 patients with HCM caused by the Asp175Asn substitution of the alpha-tropomyosin gene (TPM1-Asp175Asn) and 9 healthy volunteers. LV mass and segmental wall thickness were measured with MRI. Presynaptic cardiac adrenergic activity was measured with (123)I-metaiodobenzylguanidine (MIBG) SPECT. Global and segmental washouts of (123)I-MIBG were calculated.


RESULTS
Global myocardial (123)I-MIBG washout was faster in patients with TPM1-Asp175Asn than in healthy volunteers (50% +/- 9% vs. 37% +/- 8%, P = 0.001). In linear regression analysis, global (123)I-MIBG washout was associated with the LV mass index and LV maximal wall thickness index in HCM patients (r = 0.512, P = 0.018, and r = 0.478, P = 0.028, respectively). The mean (123)I-MIBG washout was higher in LV segments >/= 15 mm thick than in LV segments < 15 mm thick (56 +/- 10 vs. 49% +/- 10%, P = 0.002).


CONCLUSIONS
In patients with HCM sharing the same causal gene defect, the degree of LV hypertrophy is related to (123)I-MIBG washout, suggesting that cardiac adrenergic activity modifies phenotypic expression in HCM.
Sipola
Petri
P
Department of Clinical Radiology, University Hospital, University of Kuopio, Puijonlaaksontie 2, FIN-70210 Kuopio, Finland. petri.sipola@kuh.fi
Vanninen
Esko
E
Aronen
Hannu J
HJ
Lauerma
Kirsi
K
Simula
Sakari
S
Jääskeläinen
Pertti
P
Laakso
Markku
M
Peuhkurinen
Keijo
K
Kuusisto
Johanna
J
Kuikka
Jyrki T
JT
D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics*; D000328:Adult; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D017023:Coronary Angiography; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D010802:Phylogeny; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013223:Statistics as Topic
D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; D009638:Norepinephrine