Pathophysiology of heart failure

Abstract

Heart failure is an epidemic disease which affects about 1% to 2% of the population worldwide. Both, the etiology and phenotype of heart failure differ largely. Following a cardiac injury (e.g., myocardial infarction, increased preload or afterload) cellular, structural and neurohumoral modulations occur that affect the phenotype being present. These processes influence the cell function among intra- as well as intercellular behavior. In consequence, activation of the sympathoadrenergic and renin-angiotensin-aldosterone-system takes place leading to adaptive mechanisms, which are accompanied by volume overload, tachycardia, dyspnoea and further deterioration of the cellular function (vicious circle). There exists no heart failure specific clinical sign; the clinical symptomatic shows progressive deterioration acutely or chronically. As a measure of cellular dysfunction, the level of neurohormones (norepinephrine) and natriuretic peptides (e.g., NT-pro BNP) increase. For the diagnosis of heart failure, noninvasive (echocardiography, NMR, NT-proBNP) and invasive (heart catheterization, biopsy) diagnostic procedures are implemented. Modulation of the activated systems by ß-blocker, ACE-inhibitors and ARNI improve outcome and symptoms in heart failure patients with left ventricular dysfunction. Interventional and surgical therapy options may be performed as well. The understanding of the underlying pathophysiology of heart failure is essential to initiate the adequate therapeutic option individually for each patient. Furthermore, prevention of cardiovascular risk factors is essential to lower the risk of heart failure.

Keywords: HFpEF; HFrEF; Heart failure; pathophysiology; treatment of heart failure.

Figure 1

The phenotype of the heart may be predominantly excentric (e.g., following volume overload, myocardial infarction), concentric (e.g., following pressure overload, aortic stenosis) or a combination of both. The adaptive remodeling (change in LV mass, volume, structure) is influenced by the phenotype, comorbidities (e.g., diabetes), risk factors (e.g., hypertension) and by the damaging factors (e.g., myocardial stress following volume load after NSAR treatment; high heart rate). The left ventricular ejection fraction depends on filling pressure and volume. Permanent overload initiates structural remodeling with chamber dilatation and shift of the pressure-volume relationship which further deteriorate cardiac function.

Figure 2

Shematic Pressure (P)-Volume (V)-Relationship in non-failing hearts (normal) and in situations with decreased afterload, increased afterload, inotropic stimulation and decreased inotropy.

Figure 3

Neuroendocrine activation in human heart failure lead to elevation of several neuroendocrine and natriuretic peptides (red arrows). ACE, angiotensin converting enzyme; Ang´en, angiotensinogen; ANG I/II, angiotensin I/II; AT1/2R, angiotensin receptor 1/2; CO, cardiac output; SVR, systemic vascular resistance; Treatment option in green: BB, beta blocker; MRA, mineralocorticoid receptor antagonist; ACEI, ACE inhibitor; ARB, AT blocker; ARNI, Angiotensin-Receptor-Neprilysin-Inhibitor.

Figure 4

Interaction of angiotensin II and natriuretic peptide pathways in human heart failure. The detrimental action of angiotensin II via AT1- receptors may be inhibited by AT1-receptor antagonists (e.g., valsartan); the breakdown of natriuretic peptides by action of neprilysin may be inhibited by the neprilysin-inhibitor sacubitril.

Figure 5

Contraction coupling in nonfailing cardiac myocytes and changes (red arrow) in ion concentration as well as alterations in expression/function of transporters/receptors in human heart failure. See description in the text. ETC, electron transporter chain; ß1-AR, ß1 adrenoreceptor.