Number 27, 2005
Metabolic approach in heart failure
Metabolic approach in heart failure
 Back to the Summary
Graham Jackson
Cardiothoracic Centre,
St.Thomas' Hospital,
London,
UK
Correspondence: Dr Graham Jackson,
Cardiothoracic Centre,
St. Thomas' Hospital,
London
SE1 7EH,
UK.
E-mail: graham@jacksonmd.fsnet.co.uk
Heart failure occurs when the heart is unable to maintain cardiac output to accommodate metabolic requirements and the venous return [1]. It is important because it is common (1–2% of the population and 10–20% in the very elderly), disabling symptomatically, and deadly, with a mortality rate worse than that of cancer (24% 3-year survival, compared with: breast cancer 72%, prostate cancer 55% and colon cancer 42%) [2]. The classical sequence of events of failure begetting failure reflects the neurohormonal response to a reduction in ventricular function [3] (Figure 1).
Figure 1. Sequence of events leading to heart failure.
Treatment focuses on reducing symptoms, increasing exercise capacity and quality of life, and improving survival. Diuretics address volume overload and relieve symptoms, and angiotensin-converting enzyme inhibitors, angiotensin II antagonists and ß-blockers target the neurohormonal responses, both improving symptoms and reducing mortality [4]. Despite the use of all evidence-based therapies, cardiac resynchronization therapy, and implantable cardiac defibrillators, the outlook remains grim [5]. An additional symptomatic and prognostic treatment is needed, in addition to a more aggressive approach to prevention.
As long ago as 1990, Brottier et al [6] reported improved left ventricular function in patients with severe ischemic cardiomyopathy after 6 months of treatment with trimetazidine. Since then, this metabolic strategy has repeatedly been shown to improve clinical status and left ventricular ejection fraction [7]. In the most recently reported study, trimetazidine was added to up-to-date usual treatment for up to 18 months, resulting in a significant improvement in functional ability, left ventricular function, and the remodeling process in 61 patients with dilated ischemic cardiomyopathy [8]. The beneficial pharmacological intervention with trimetazidine, which shifts metabolism from free fatty acid to glucose oxidation, suggests a cytoprotective affect on the myocardium, with enhancement of carbohydrate oxidation increasing cardiac contractility – the heart prefers glucose as its energy source.
In this issue of Heart and Metabolism, we explain, expand, and build on the metabolic story – moving from the basic concepts of a metabolic approach to the clinical context. The efficacy of metabolic agents is reviewed, and the role of trimetazidine expanded on with a clinical example.
The failing heart needs help and addressing the metabolic aspects of cardiac failure offers it assistance in addition to the other established strategies. A survival benefit from metabolic treatment needs long-term outcome studies, and these appear to be justified on the basis of accumulating evidence to date with trimetazidine. ?
Back to the Summary
REFERENCES
1. Task Force of the Working Party on Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis of heart failure.
Eur Heart J. 1995;16:741–751.
PMID: 7588917 [PubMed - indexed for MEDLINE]
2. Millane T, Jackson G, Gibbs CR, Lip GYH.
Acute and chronic management strategies.
ABC of Heart Failure. London: BMJ Books 2000;33–36.
3. Packer M.
The neurohormonal hypothesis: a theory to explain the mechanisms of disease progression in heart failure.
J Am Coll Cardiol. 1992;20:248–254.
PMID: 1351488 [PubMed - indexed for MEDLINE]
4. Task force for the Diagnosis and Treatment of Chronic Heart Failure. European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure.
Eur Heart J. 2001;22:1527–1560.
PMID: 11492984 [PubMed - indexed for MEDLINE]
5. Lane RE, Cowie MR, Chow AWC.
Prediction and prevention of sudden cardiac death in heart failure.
Heart. 2005;91:674–680.
PMID: 15831662 [PubMed - indexed for MEDLINE]
6. Brottier L, Barat L, Combe C, et al.
Therapeutic value of a cardioprotective agent in patients with severe ischemic cardiomyopathy.
Eur Heart J. 1990;11:207–212.
PMID: 2318223 [PubMed - indexed for MEDLINE]
7. Lee L, Horowitz J, Frenneaux M.
Metabolic manipulation in ischaemic heart disease, a novel approach to treatment.
Eur Heart J. 2004;25:634–641.
PMID: 15084367 [PubMed - indexed for MEDLINE]
8. Di Napoli P, Taccardi AA, Barsotti A.
Longterm cardioprotective action of trimetazidine and potential effect on the inflammatory process in patients with ischaemic dilated cardiomyopathy.
Heart. 2005;91:161–165.
PMID: 15657223 [PubMed - indexed for MEDLINE]
Back to the Summary
|
