New Concept in Treatment of Heart Failure

When I was in medical school, heart failure was managed with diuretics and digoxin. Diuretics are still with us but digoxin is long gone. Digoxin is an inotrope, which means that it increases cardiac output by trying to increase the force of myocardial conrtactions.

By late 70s, the work of Hajmasson showed us that beta-blockers like metoprolol was good for heart failure from dilated cardiomyopathy.The theory being that when the heart is weak and their metabolism is clearly exhausted, flogging it harder by the use of inotropes was self defeating in the medium and long term. Resting the heart and readjusting the threshhold of the beta-receptors, was better, and the clinical data seems to suggest that too.

The role of Dilatrend, bucinprolol, and metoprolol succinate is no longer in doubt. They are all in the guidelines. For the first time, we could prove that beta-blockers not only improve the quality of life but also the quantity of life (something which neither diuretics, digoxin, venodilators or vasodilators could do).

In the 80s we went through a phase of venodilators and vasodilators for CCF, the phase of pre-load and afterload reduction. Very soon we learnt that heart failure was actually an adaptive mechanism gone wrong. When cardiac output falls, the RAAS system kicks in, in an attempt to maintain blood pressure, causing vasoconstriction and increase peripheral vascular resistance. This increased PVR maintains BP and blood flow to vital organs. This however is shortlived, as an increase in PVR will almost certainly cause more afterload aand pressure on a failing heart. The ACE-I allowed us to modulate the overactive RAAS in heart failure, with great effect and allowed us to make our patients with heart failure live longer and better, captopril being a good example. But alas, like all good men, they had a flaw.

We soon learnt that ACE-I can cause an irritating cough, almost in 30% of patients. ARB (angiotensin receptor blocker) and end-system blocker was discovered. They had many of the properties of ACE-I but without the cough. Although they were often touted as an expensive ACE-I minus the cough, they really did not have the same credentials. ACE-I had many clinical trials to prove their efficacy, especially their benefit in terms of mortality reduction. We are still lacking in ARB data in terms of mortality reduction. Almost certainly, they improve the quality of life, with less hospitalisation. They were also shown to be equivalent to captopril in the Valiant Trial, but alas, they were never shown on their own to be better then placebo, in reducing mortality.

I fear that it will never be tested like that, because we have reach an era where it may no longer be ethical to test new heart failure drugs against placebo. All heart failure patients must at least receive a betablocker or an ACE-I. Well, what a long review. I actually started by trying to highlight the fact that an old drug, trimetazidine, has found a new use. Trimetazidine (TMZD) is a common drug used to lessen angina. TMZD is a partial fatty acid oxidation inhibitor. By shifting the metabolism from a fatty acid base metabolism to a glucose base metabolism, with TMZD, there is improvement in symptoms. and also an improvement in LV EF. But this study was with a small number of patients, and then only over 13 months. So we will never show reduction in mortality. These findings were reported by the Italians at the september issue of the Journal of the American College of cardiology. But conceptually, TMZD is a very interesting agent. I must say that I have never used in for heart failure, nore with angina, but I will certainly give it a try, now that I know.