Heart failure (HF) can be clinically defined as a syndrome in which patients have typical symptoms (e.g., breathlessness, ankle swelling) and signs (e.g., elevated jugular venous pressure, pulmonary crackles) resulting from an abnormality of cardiac structure or function [1].

Chronic heart failure (CHF) can be caused by several types of cardiac dysfunction and is most commonly due to left ventricular dysfunction. An isolated right ventricular (RV) dysfunction is very rare, and generally RV involvement is secondary to left ventricular (LV) dysfunction.

Demonstration of an underlying cardiac cause is essential to diagnose HF as the precise pathology determines the specific treatment used. More recently, CHF has been classified into two categories: HF due to LV dysfunction even called HF with reduced ejection fraction (HF-REF or systolic heart failure) and HF where only a diastolic dysfunction is detectable called HF with preserved ejection fraction (HF-PEF or diastolic heart failure). 1 HF-REF is the best understood type of HF in terms of pathophysiology and treatment and is the focus of this chapter.

Furthermore, HF can present either as a chronic condition or acutely, occurring de novo, or as a decompensation of CHF. The purpose of this chapter is to cover CHF, while acute heart failure is discussed in another section of this book.

CHF prevalence is 1–2 % of the population, and the prevalence increases to approximately 15 % in the elderly [2]. At least half of patients with HF have a low EF, and approximately 50 % of patients with significant LV systolic dysfunction have no symptoms or signs of heart failure. HF occurs more frequently in male rather than female sex.

The causes of CHF are listed in Table 8.1. There is a geographical variation regarding the etiology of CHF. In Western countries two-thirds are secondary to ischemic disease, and other important contributors are hypertension, valve disease, and alcohol. Rheumatic disease still remains the most common cause of CHF in the developing countries, while Chagas disease is frequent in South America.

Left ventricular dysfunction is associated with hemodynamic, autonomic, neurohumoral, and immunological changes.

The term “systolic dysfunction” refers to a decrease in myocardial contractility and consequently a decrease in cardiac output. Signs and symptoms of HF are due in part to compensatory mechanisms utilized by the body in an attempt to adjust for a primary deficit in cardiac output. Many of the processes involved in sustaining HF are maladaptive which means that they were originally designed to maintain blood pressure and vital organ perfusion.

Decrease of cardiac output leads to an increase of:

Based on the Frank–Starling law, the initial increase of left ventricular end-diastolic pressure is initially compensated by an increase of contractility, but as the increase persists, the myocardium fails and cardiac output drops.

Neurohumoral adaptations, such as activation of the renin–angiotensin–aldosterone and sympathetic nervous systems by the low-output state, can contribute to maintenance of perfusion of vital organs in two ways:

The principal neurohumoral systems involved in the response to HF are the sympathetic nervous system, the renin–angiotensin–aldosterone system (RAAS), and antidiuretic hormone [3, 4, 5]. One of the first responses to a decrease in cardiac output is activation of the sympathetic nervous system, resulting in both increased release and decreased uptake of norepinephrine at adrenergic nerve endings. The effects of high circulating concentrations of epinephrine and norepinephrine include:

The decrease of cardiac output leads to a reduction of renal afferent arteriolar blood flow causing secretion of renin and, subsequently, production of angiotensinogen and angiotensin I. The angiotensin I is then converted by the ACE present in the lung to angiotensin II. There is also evidence that angiotensin II can be synthesized locally at a variety of tissue sites including the kidney, blood vessels, adrenal gland, and brain [6].

Angiotensin II increases aldosterone release, inducing systemic and renal vasoconstriction. Furthermore, angiotensin II can act directly on myocytes and in the myocardium to promote pathologic remodeling as myocyte hypertrophy, re-expression of fetal protein isoforms, myocyte apoptosis, and alterations in the interstitial matrix. Aldosterone-mediated effects are sodium and water retention and hypokalemia resulting in pulmonary and peripheral edema and increased afterload. Activation of the carotid sinus and aortic arch baroreceptors by the low cardiac output in heart failure leads to enhanced release of antidiuretic hormone and stimulation of thirst. Elevated levels of ADH may contribute to the increase in systemic vascular resistance in HF via stimulation of the V1A receptor, which is found on vascular smooth muscle cells, and also promote water retention via the V2 receptor by enhancing water reabsorption in the collecting tubules. The combination of decreased water excretion and increased water intake via thirst often leads to a fall in the plasma sodium concentration. The degree of hyponatremia is an important predictor of survival in these patients.

The increased LV and left atrium wall stretch due to raised left ventricular end-diastolic pressure leads to secretion of the natriuretic peptide hormones. The types of natriuretic peptide hormones which circulate in high concentration in HF are:

Brain natriuretic peptides

Atrial natriuretic peptides (ANP and NT-ANP)

These peptides cause:

Plasma ANP levels rise early in the course of the disease and have been used as a marker for the diagnosis of asymptomatic left ventricular dysfunction.

All these processes are responsible for sodium and water retention and a progressive depression of myocardial function. The last step of this fall is an adverse remodeling of the left ventricle involving myocyte hypertrophy, death, and fibrosis.