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Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed.

Copyright 2007 Saunders, An Imprint of Elsevier

PATHOGENESIS

As shown in Figure 22-1 , HF may be viewed as a progressive disorder that is initiated after an index event either

damages the heart muscle, with a resultant loss of functioning cardiac myocytes, or alternatively disrupts the ability of the

myocardium to generate force, thereby preventing the heart from contracting normally. This index event may have anabrupt onset, as in the case of a myocardial infarction (MI); it may have a gradual or insidious onset, as in the case of

hemodynamic pressure or volume overloading; or it may be hereditary, as in the case of many of the geneticcardiomyopathies. Regardless of the nature of the inciting event, what is common to each of these index events is that

they all, in some manner, produce a decline in pumping capacity of the heart. In most instances patients will remain

asymptomatic or minimally symptomatic following the initial decline in pumping capacity of the heart, or will developsymptoms only after the dysfunction has been present for some time. Although the precise reasons why patients with LV

dysfunction remain asymptomatic are not certain, one potential explanation is that a number of compensatory

mechanisms become activated in the setting of cardiac injury or depressed cardiac output and appear to modulate LV

function within a physiological/homeostatic range, such that the functional capacity of the patient is preserved or is

depressed only minimally. However, as patients transition to symptomatic HF, the sustained activation of neurohormonaland cytokine systems leads to a series of end-organ changes within the myocardium, referred to collectively as LV

remodeling. As discussed later, LV remodeling is sufficient to lead to disease progression in HF independent of the

neurohormonal status of the patient.

FIGURE 22-1 Pathogenesis of heart failure (HF). HF begins after an index event produces an initial decline in pumping capacity of theheart. Following this initial decline in pumping capacity of the heart, a variety of compensatory mechanisms are activated including theadrenergic nervous system, the renin angiotensin system, and the cytokine systems. In the short term these systems can restorecardiovascular function to a normal homeostatic range with the result that the patient remains asymptomatic. However, with time the sustained

activation of these systems can lead to secondary end-organ damage within the ventricle, with worsening LV remodeling and subsequentcardiac decompensation. As a result of this worsening LV remodeling and cardiac decompensation, patients undergo the transition from

asymptomatic to symptomatic HF. (From Mann DL: Mechanisms and models in HF: A combinatorial approach. Circulation 100:99, 1999.)

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