What does the future hold for the management of chronic heart failure?
1 Department of Cardiology, University of Pavia and Policlinico S. Matteo IRCCS, Pavia, Italy
2 Policlinico di Monza, Monza, Italy
3 University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
* Corresponding author. Tel: +39 2382 503 934; fax: +39 2545 76 66. E-mail address: evanoli{at}compuserve.com
Sudden cardiac death (SCD) represents a major challenge in managing chronic heart failure (CHF). There is extensive evidence of the antifibrillatory action of beta-blockers and their ability to prevent SCD in patients with CHF and left ventricular (LV) dysfunction following myocardial infarction (MI). In contrast, angiotensin-converting enzyme-inhibitors have minimal effects on SCD risk, reducing mortality primarily by preventing or delaying pump failure. The mechanisms by which beta-blockers reduce lethal arrhythmias and thereby prevent SCD mostly reflect blockade of the beta1-subtype. Dog models have been used to investigate ventricular remodelling and arrhythmogenesis after MI; dogs with chronic ischaemic LV dysfunction susceptible to SCD have depressed vagal and elevated sympathetic control of heart rate coupled with abnormal repolarization. Furthermore, susceptibility to SCD appears to be associated with non-uniform catecholamine release within the left ventricle. Cardiac nerve sprouting and sympathetic hyperinnervation consequent to ischaemic neural damage are important co-factors causing ventricular electrical dyshomogeneity and, thus, malignant tachyarrhythmias and SCD. Regulating nerve growth factor and growth-associated protein 43 expression after MI might provide a means of controlling arrhythmias and preventing SCD. An intriguing possibility might be the prevention of cardiac norepinephrine spillover by means of gene therapy to increase expression of the norepinephrine transporter molecule uptake-1. At this stage, the evidence from clinical trials, and especially that from Cardiac Insufficiency Bisoprolol Study III, strongly supports the use of selective beta-adrenergic blockade as a primary intervention in the management of patients with CHF.
Key Words: Heart failure • Sudden death • Autonomic nervous system • Adrenergic blockade
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