HF is a Progressive Disease¹

CHF is an insidious, progressive disease unless slowed or stopped by treatment.¹ Left ventricular dysfunction begins with some injury to or stress on the myocardium and is generally a progressive process, even in the absence of a new identifiable insult to the heart. The principal manifestation of the progression is a process called cardiac remodeling. Remodeling describes a progressive process characterized by molecular, cellular and interstitial changes resulting in alteration in size, shape and function of the heart arising from cardiac injury or overload. This process is manifested by a change in the geometry of the left ventricle where the chamber dilates, hypertrophies and becomes spherical. This change in chamber size increases the hemodynamic stresses on the walls of the failing heart and depresses its mechanical performance. In addition, it increases the magnitude of regurgitant flow through the mitral valve. These effects serve to sustain and exacerbate the remodeling process.¹

Due to the lack of symptoms, many affected individuals are in the relatively late stages of disease by the time they are diagnosed and treated, resulting in some dismal statistics:⁵

• After the first hospitalization, the 5-year survival rate is only:
  - 30% for men 67-74 years of age
  - About 20% for men 75-84 years old
  - 15% for those > 85 years
  
• Survival in women is slightly better, suggesting the possibility of important gender differences in the disease.

Source: R.S. Vasan, et al. Arch Intern Med. 1996.⁶

Source: E. Braunwald. Heart Disease: A Textbook of Cardiovascular Medicine. 2001.⁷

Cardiac remodeling generally precedes the onset of symptoms by months and even years. It also continues after the development of symptoms and contributes to the worsening of symptoms despite treatment.¹

Many mechanisms may be involved in the acceleration of cardiac remodeling. There is substantial evidence that the activation of endogenous neurohormonal systems may play an important role in cardiac remodeling and, thereby, in the progression of HF. Patients with HF have elevated circulating or tissue levels of norepinephrine, angiotensin II, aldosterone, endothelin, vasopressin and cytokines, which may act individually or in combination to adversely effect the structure and function of the heart. These neurohormonal factors cause sodium retention and peripheral vasoconstriction, which increase the hemodynamic stress on the ventricle. They may also exert direct toxic effects on cardiac cells and stimulate myocardial fibrosis, which can further alter the architecture and impair the performance of the failing heart.¹

Recognizing that, like coronary artery disease, HF has:

• Established risk factors
• Structural prerequisites
• Symptomatic and asymptomatic phases

Most importantly, specific treatments targeted at each stage can either prevent or reduce the morbidity and mortality associated with HF.^1,2

Because treatment is most effective when prescribed at an early stage of disease,⁴ a reliable indicator of prognosis may help optimize planning therapeutic strategies in individual patients.⁵

References