Download Uncomplicated Acute Myocardial Infarction Results in Protracted

16P
Medical Research Society
M39
Uncomplicated Acute Myocardial Infarction Results in
Protracted Sympathetic Hyperactivity After Discharge From
Hospital
LN Graham, PA Smith, JB Stoker, AF Mackintosh, DA Mary.
Department of Cardiology, St James’s University Hospital,
Leeds, UK
Background: No information exists on the magnitude of
sympathetic nerve activity and its changes over time following acute
myocardial infarction (AMI). This information is required because
activation of sympathetic drive is important in relation to morbidity
and mortality. It is known that elevated levels of plasma
catecholamines occur following uncomplicated AMI. However, this
is an indirect index of sympathetic drive and returns to normal values
within a week, despite the persistence of autonomic dysfunction for
longer. Therefore we planned to quantify the central sympathetic
output to the periphery following uncomplicated AMI, and
investigate its progress up to six months after discharge from
hospital.
Methods: We examined 12 patients (age range 48 to 71 years) 2-4
days following AM1 and again after 3 and 6 months. None had
clinical complications. All were on conventional therapy which
remained unchanged throughout the study. Twelve healthy control
subjects matched for age and body mass index were also studied.
Muscle sympathetic nerve activity was measured from the peroneal
nerve by microneurography. We quantified the central sympathetic
output as the mean frequency of single units with defined
vasoconstrictor properties. This was expressed in terms of impulses
per 100 cardiac beats (imp1100b). Data were expressed as mean f
SEM.
Results: The sympathetic activity early after AM1 (95 f 6 . 3
imp/100b) did not change at 3 months (92 k4.7 imp/100b) but
decreased after 6 months (80 f 4 . 8 imp/100b; p<O.Ol, ANOVA).
These were still greater (p<O.OI) than control group values (57 f 4.8
imp/100b). There were no significant changes in arterial pressure or
body mass index. The sympathetic hyperactivity was inversely
correlated to left ventricular ejection fraction (at least r=-0.65;
p<0.02).
Conclusions: It was shown that a protracted state of sympathetic
hyperactivity occurs following uncomplicated AMI.This could arise
because of impairment of reflexes from cardiac receptors and may at
least in part explain delayed morbidity and mortality following AMI.
M40
Hypertrophic Cardiomyopathy fibrosis imaging by MRI
J. Moon.
Department of MRI, Royal Brompton Hospital, London, SW6
3LL
Background: Hypertrophic Cardiomyopathy (HCM) is complicated
by sudden death and cardiac failure. Characteristic autopsy
histology includes myocardial disarray and macroscopic fibrosis.
We hypothesised that gadolinium enhanced CMR could demonstrate
fibrosis in HCM and be linked to clinical events.
Methods:
A blinded, case matched prospective study with
predefined primary statistical analysis. 40 HCM patients were
matched for the number of clinical risk factors for sudden death and
for the presendabsence of adverse remodelling (progressive
disease). Gadolinium enhanced CMR was performed. LV function,
mass, total myocardial enhancement and enhancement pattern were
assessed.
Results:
31 (77%) of patients had contrast enhancement
representing fibrosis. The mean percentage of myocardial fibrosis in
the LV was 10.7% (04%).There was more fibrosis in patients with
progressive disease (21% vs 9.196, p=0.002). In patients without
progressive disease, patients at high risk of sudden death had more
fibrosis (9.7% vs 5.2796, pd.05) as did patients with a history of
VT/VF (12.1% vs 5.91%, pd.04). Different patients had different
patterns of fibrosis (figure 1) and may have different clinical
outcomes.
Conclusion: Gadolinium enhanced CMR identifies and quantifies
HCM fibrosis in-vivo. Fibrosis represents the abnormal myocardial
substrate of HCM which may be a final common pathway for
morbidity and mortality.
Figure 1: a short axis contrast enhanced view in 4 patients; left to
right: normal, fine diffuse fibrosis, subendocardial and confluent
block fibrosis.
M41
Genetic variation of the beta-1 adrenoceptor affects left
ventricular mass
T Stanton, S Padmanabhan, A G Jardine, A McConnachie, M
Upton, G Watt, A F Dominiczak, J M C Connell.
Left ventricular (LV) mass is an important cardiovascular risk factor.
The beta-I adrenoceptor (BIAR) is a key cell surface signalling
protein expressed in the heart and it’s variation may, therefore, affect
LV mass. The gene of the BlAR has two known functional
polymorphisms; one of these changes the nucleic acid sequence from
guanine(G) to cytosine(C) at position 1165, conferring an amino acid
change at position 389 from glycine to arginine. This area is critical
for G-protein coupling and so cell signalling. The arginine-form of
the receptor has been demonstrated to have increased GTP binding’.
We therefore examined the relationship between this variation in the
DlAR gene and the effect on LV mass in 2 populations. The first
study consisted of 262 patients attending a renal clinic, 40% of
whom were on renal replacement therapy(RRT). LV mass index
(LVMI) was calculated from echocardiography and b l d drawn for
DNA extraction. Individuals were categorised CC if both alleles
encoded for arginine at position 389, GG if both alleles encoded for
glycine. There was a highly significant difference in LV mass
between the GG group when compared to the other 2 groups,
CGGG p= 0.022 and CC:GG p=0.009. This relationship
strengthened further when patients on RRT were omitted (CC:GG p
<O.OoOl).
In a second study, the effect of genotype on
electrocardiographically measured LV mass was studied. 2280
subjects were genotyped for the PlAR polymorphism.
No
significant difference was found between LVMI and genotype after
correction for age, BP and height and analysing separately for sex.
In summary, no influence of the genotype on ECG defined LV mass
was noted. In contrast, positive findings were obtained when
echocardiography was used to measure LV mass in renal patients.
It is therefore possible that genetic variation of the beta-1
adrenoceptor is of greater importance in defining LV mass in
pathological circumstances.
Reference: 1. Mason DA et al. J B i d Chem, 1999,274, 12670-4.