Remodelling refers to the self perpetuating process seen in heart failure which leads to structural changes and functional deterioration of the myocardium. The initial insult to the heart may be ischemic, chemical, genetic, inflammatory or unknown (idiopathic) The initial changes in physiology are compensatory in the short term and probably evolved to deal with acute hypovolemia. These predominantly neurohormonal changes lead to eventual alterations in ventricular size, shape and function known as remodelling. Remodelling and further loss of effective cardiac function leads to further neurohormonal alterations, and further impaired pump function.
The primary neurohormonal changes seen are:
- Chronic sympathetic nervous system activity
- Stimulation of Renin-Angiotensin-Aldosterone (RAA) system
This leads to:
- Adrenoceptor downregulation
- Altered calcium handling
- Myocyte necrosis / apoptosis
- Myocyte hypertophy and impaired contractility
- Altered cytoskeleton proteins
- Myocardial fibrosis
- Myocardial thinning
All of which leads to further impairment of pump function, neurohormonal dysfunction, ventricular dilatation, increased wall stress (Laplace's law) and a self perpetuating process of remodelling.
Sodium and water retention secondary to these neurohormonal alterations is probably more responsible for the oedema of heart failure than pump failure itself. The few drugs shown to reduce mortality in heart failure are those which block aspects of the neorohormonal changes seen in heart failure, namely beta blockers, angiotensin converting enzyme inhibitors and aldosterone antagonists such as spironolactone.
Interestingly, many aspects of remodelling can be reversed, so-called reverse remodelling. The use of a combination of drugs and mechanical circulatory support in a technique known as Bridge to recovery looks promising for the treatment of end stage heart failure.