Recently, Italian Cardiology has undergone profound changes. This editorial relates to the β-blockers which were traditionally contraindicated but are nowadays indicated in the treatment of heart failure. The 'leit motif' of this editorial is that heart failure is a clinical syndrome (and not only a cardiac disease), of which, unfortunately, we have rather poor knowledge. Moreover, the rational hypotheses have never matched the pathophysiology nor the therapeutic (e.g. positive inotropic compounds) picture of the syndrome. On the contrary, 'irrational' hypotheses have resulted in unexpected findings as is the case of the β-blockade. In fact, who would have wagered that a condition which has its origins in a reduced contractility capacity of the heart, has to be treated with negative inotropic compounds such as β-blockers? Actually, in the last decade, the pathophysiological perception of heart failure has radically changed. Heart failure is now considered as a disorder which recognizes its primum movens at the cardiac level. However, as the syndrome progresses, it results in a series of alterations involving the neuroendocrine system, cytokines, the endothelium and various other organs. Thus, the therapeutic target has moved from the center (positive inotropic compounds) to the periphery (with drugs able to inhibit the neuroendocrine response such as ACE-inhibitors, anti-aldosteronics and β-blockers). We know that cultural revolutions of this degree require a great deal of time before being accepted and applied. This was the case of ACE-inhibitors and it will be so for anti-aldosteronics. As far as β-blockers are concerned, the situation is probably more complicated. This is the purpose of this editorial program which aims at implementing the use of β-blockers in clinical practice. In fact, we all agree on the 'case of β-blockade in heart failure': a) a series of clinical trials have shown their prognostic value and, paradoxically, also their therapeutic advantage; b) we are 'bombed' by medical congresses that aim at stressing the increased advantage of β-blockers; c) guidelines clearly state their efficacy. In daily practice, the Italian Cardiological Community is increasing the use of β-blockers (data from > 11 000 patients with chronic heart failure relevant to the IN-CHF database of ANMCO show that 18% of the patients are being treated with α-blockers). However, a certain indecision is apparent especially since some categories of patients have not been considered in these trials. The study groups on heart failure of ANMCO and SIC together formulated the idea of 'walking the reader through' the 'case of β-blockade in clinical practice' in order to avoid the gap between the 'theoretic convictions' and 'daily practice'. However, this 'gap' is quite understandable, especially in our country, which, quite honestly, does not come from a culture of β-blocker usage which is typically Anglo-Saxon. Again, this 'gap' is quite understandable because β-blockers should be used - with caution - at least in the initial stages of the syndrome in order to reach the best dosage over time, i.e. the maximum tolerated dosage. During this phase, the patient could undergo a symptomatic worsening (which must be treated with an adjustment of the concomitant treatment). Thus, patients should be psychologically convinced that this type of treatment is useful and should not give up today that from which they could reap benefits tomorrow. In other words, to reach the dosages suggested by data from the literature, both the doctor and the patient must believe in this therapeutic approach. The worsening in symptoms is probably due to the 'pharmacological' effects of β-blockers, which, typically, reduce the inotropism and the chronotropism without affecting the afterload (with some exceptions). As a consequence, during the initial phases of treatment, ejection fraction decreases and asthenia increases. However, over time (usually after 2-3 months), the ventricular volumes decrease (or, at least, they do not further increase), ejection fraction tends to increase and symptoms improve. Therefore, β-blockers transform themselves from negative to positive inotropic compounds in heart failure! The reason must be found at the molecular level: the noradrenaline released at autocrine and paracrine levels is a potent stimulator of this chain of events, which, in the end, results in a phenotypic switch versus embryonal characteristics, at the cardiac level. In other words, the myocytes, as a consequence of the impaired and prolonged sympathetic stimulation (among others), change their genetic characteristics and return to the embryonal phenotype. This phenotype 'accepts' stimuli of cell growth (which, in adult myocytes, result in pathological hypertrophy, since they cannot duplicate) and apoptosis (which, in adult myocytes, result in a clear mass loss always due to the impossibility of duplication). Both these effects are not definitely useful, however, their blockade (or even a reduction of their activity) is advantageous to the slowing-down of the progression versus ventricular remodeling. At the membrane level, β-blockers interrupt the communication between noradrenaline and the intracellular systems affecting this chain of events, which is often self-maintained. If this does not occur, the 'pharmacological' effects prevail tout court, thus the symptoms worsen until the 'biological' effects do not prevail. The differentiation between the pharmacological and biological effects of a drug is fundamental in a chronic clinical syndrome such as heart failure in which the enemy to combat (at the biological level) is often invisible or clinically not available. The cultural initiative of this editorial faces a conceptual revolution both at biological and clinical levels. The cardiologist is taken 'by the band' when dealing with a patient with a preserved or markedly impaired systolic function, or is elderly. We aim at giving the cardiologist a neat revision of clinical trials, taking into consideration the suggestions and - the too often emphasized contraindications - that result from such trials. Lastly, we will touch upon the cooperation that the Italian Cardiological Society has already rendered in the past and indeed will continue in the future. We thank the authors for their contribution.
|Translated title of the contribution||The daily practice in heart failure: The 'case' of the beta-blockade: Introduction|
|Number of pages||3|
|Journal||Italian Heart Journal Supplement|
|Publication status||Published - 2000|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine