The cardiovascular community has awaited the new ESC-guidelines on acute heart failure (AHF) with considerable interest (1).
According to these the clinical condition “acute heart failure” is defined as “rapid onset of symptoms and signs secondary to abnormal cardiac function”.
The guidelines explain that the condition may occur with or without previous cardiac disease. Cardiac dysfunction can be related to systolic or diastolic failure, to abnormalities in cardiac rhythm, or to pre- and afterload mismatch, all of which often represent life threatening situations requiring urgent treatment.
The guidelines classify the syndrome of AHF into 6 clinical groups. Of these, both “acute decompensated heart failure”, “pulmonary edema” and “low cardiac output syndrome” are some of the commonest reasons for hospitalisation, yet the mortality remains high despite medical treatment.
Treatment of AHF
Surprisingly, standard treatment of patients with AHF has been unchanged for several decades. For “acute decompensated heart failure” basic therapy has been morphine and diuretics, for “pulmonary edema” vasodilating drugs in addition such as nitrates, and for the “low cardiac output syndrome” inotropic drugs.
Recent evidence has shown that conventional treatment can be used more adequately, or be replaced by new drugs (Table).
Cotter et al. (2) have shown that administration of high doses of nitrates given to patients with pulmonary edema is more effective than standard vasodilating treatment with low dose nitrates and high doses of diuretics, probably due to an additional reduction in afterload.
Two “new” vasodilating drugs have been evaluated in randomised clinical trials. Torre-Amione et al. (3) and the “VERITAS”-trialists (4) showed that tezosentan, a dual endothelin-antagonist, can bring on an improvement in hemodynamics in patients with AHF, however the VERITAS-study, interrupted prematurely after 1400 included patients had been enrolled, failed to show improvement in dyspnea and mortality/morbidity.
Nesiritide, which is the synthetic recombinant BNP already approved by the FDA for the indication of AHF, has shown to confer both hemodynamic and symptomatic alleviation above that of placebo or glyceroltrinitate (5, 6).
Use of inotropic drugs in patients with severe acute heart failure without signs of peripheral hypoperfusion has been a matter of considerable debate. Recent evidence demonstrates that, despite hemodynamic improvements, the synthetic beta receptor agonist dobutamine (7) as well as the phosphodiesterase-inhibitor milrinone (8) confer higher mortality in AHF patients, that is likely due to an increased incidence of myocardial infarctions and ventricular tachyarrhythmias.
Hence, according to the new guidelines, dobutamine is only indicated in AHF patients with signs of peripheral hypoferfusion (hypotension or decreased renal function) with or without congestion and who are refractory to diuretics and vasodilators at optimal doses.
Likewise, milrinone should be restricted to patients with preserved systolic blood pressure or preferred to dobutamin in patients on concomitant beta-blocker therapy.
Levosimendan, a new calcium-sensitiser, induces its positive inotropic effect through calcium sensitisation at the level of the contractile proteins, as well as a vasodilatatory effect via ATP-sensitive potassium channels. Levosimendan has shown favorable hemodynamic effects and, as the only compound so far, reduced mortality in AHF (9).
Taken together, state-of-the-art treatment of AHF has finally begun to evolve, for the benefit of those who suffer from this grave condition.
Table: New medications in acute heart failure, their mode of action and pharmacologic mechanism.
|Medication||Mode of Action||Mecanism|
|High dose of ISDN*||(Venous +) arterial vasodilation||Nitric Oxide (NO) -pathway|
|Tezosentan||Arterial vasodilation||Endothelin-receptor blocker|
|Nesiritide||Arterial vasodilation||Human recombinant BNP
(Brain Natriuretic Peptide)
|Levosimendan||Increased inotropy, vasodilation||Activates K-ATP channels
(*ISDN; isosorbid dinitrate)
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.