UNIVERSITY NEWS
Heart failure, myocardial ischaemia and
neurohormonal activation
Coronary artery disease has become the most important underlying aetiology for the development of chronic heart failure (CHF) in the Western world. In most of these patients, progressive coronary artery disease leads to one or more myocardial infarctions, causing left ventricular (LV) dysfunction. Aims of the thesis The first aim of this work was to study whether the condition of CHF per se was associated with changes in myocardial perfusion, and whether this could be interpreted as ischaemia. Given the importance of neurohormonal activation on CHF and ischaemia, we then evaluated the influence of the two main neurohormonal systems. We performed PET scanning in a group of patients with idiopathic dilated cardiomyopathy, and compared them with healthy volunteers. We then conducted a similar study (this time in patients with CHF and coronary artery disease) in which dobutamine stress echocardiography (DSE) was also performed. Further, we analysed the influence of the renin-angiotensin system (RAS) on myocardial ischaemia, and we studied both the effects of the sympathetic nervous system and its blockade and those of the parasympathetic nervous system and its blockade. Relation heart failure and
ischaemia In patients with CHF, myocardial flow reserve is impaired and this is related to the severity of CHF.
264
Resting myocardial flow was not affected. A significant part of the myocardium showed a perfusion/metabolism mismatch, suggesting ischaemia. Moreover, we observed ischaemia-like responses during DSE which regionally matched the PET abnormalities. Renin-angiotensin system Anti-ischaemic effects were most pronounced in patients with LV dysfunction, as compared with those with normal LV function, possibly mediated by beneficial effects on ischaemia-induced neurohormonal activation. Further, ACE inhibition showed a trend in preventing deterioration of endothelial dysfunction.
a role in the pathophysiology and the progression of this syndrome. Drug intervention can be beneficial, and the window of benefit appears to be larger as CHF becomes more advanced. More research is needed to study underlying mechanisms, including genetic and metabolic changes, which may provide more pathophysiological insight and possibly open new avenues ofdrug treatment in this devastating disease. A.F.M. van den Heuvel, doctor in training. Department of
Cardiology/T17oraxcenter,
University Hospital Groningen, Groningen.
Autonomic nervous system The results indicate that in patients with LV dysfunction, the improvement in coronary sinus blood flow and reduction in coronary vascular resistance during pacing was inhibited by beta blockade. This coincided with more systemic neurohormonal activation. The last study confirmed that atropine has anti-ischaemic effects, which were more pronounced in patients with coronary artery disease and normal LV function, compared with those with LV dysfunction. Discussion The results ofthis work suggest that coronary flow abnormalities are present in patients with LV dysfunction and CHF, that these occur early in the disease, and that they are related to the severity of CHF. These flow abnormalities may play
Netherlands Heart Journal, Volume 9, Number 6, September 2001
Heart failure, myocardial ischaemia and
neurohormonal activation
Coronary artery disease has become the most important underlying aetiology for the development of chronic heart failure (CHF) in the Western world. In most of these patients, progressive coronary artery disease leads to one or more myocardial infarctions, causing left ventricular (LV) dysfunction. Aims of the thesis The first aim of this work was to study whether the condition of CHF per se was associated with changes in myocardial perfusion, and whether this could be interpreted as ischaemia. Given the importance of neurohormonal activation on CHF and ischaemia, we then evaluated the influence of the two main neurohormonal systems. We performed PET scanning in a group of patients with idiopathic dilated cardiomyopathy, and compared them with healthy volunteers. We then conducted a similar study (this time in patients with CHF and coronary artery disease) in which dobutamine stress echocardiography (DSE) was also performed. Further, we analysed the influence of the renin-angiotensin system (RAS) on myocardial ischaemia, and we studied both the effects of the sympathetic nervous system and its blockade and those of the parasympathetic nervous system and its blockade. Relation heart failure and
ischaemia In patients with CHF, myocardial flow reserve is impaired and this is related to the severity of CHF.
264
Resting myocardial flow was not affected. A significant part of the myocardium showed a perfusion/metabolism mismatch, suggesting ischaemia. Moreover, we observed ischaemia-like responses during DSE which regionally matched the PET abnormalities. Renin-angiotensin system Anti-ischaemic effects were most pronounced in patients with LV dysfunction, as compared with those with normal LV function, possibly mediated by beneficial effects on ischaemia-induced neurohormonal activation. Further, ACE inhibition showed a trend in preventing deterioration of endothelial dysfunction.
a role in the pathophysiology and the progression of this syndrome. Drug intervention can be beneficial, and the window of benefit appears to be larger as CHF becomes more advanced. More research is needed to study underlying mechanisms, including genetic and metabolic changes, which may provide more pathophysiological insight and possibly open new avenues ofdrug treatment in this devastating disease. A.F.M. van den Heuvel, doctor in training. Department of
Cardiology/T17oraxcenter,
University Hospital Groningen, Groningen.
Autonomic nervous system The results indicate that in patients with LV dysfunction, the improvement in coronary sinus blood flow and reduction in coronary vascular resistance during pacing was inhibited by beta blockade. This coincided with more systemic neurohormonal activation. The last study confirmed that atropine has anti-ischaemic effects, which were more pronounced in patients with coronary artery disease and normal LV function, compared with those with LV dysfunction. Discussion The results ofthis work suggest that coronary flow abnormalities are present in patients with LV dysfunction and CHF, that these occur early in the disease, and that they are related to the severity of CHF. These flow abnormalities may play
Netherlands Heart Journal, Volume 9, Number 6, September 2001
