HF is a progressive heterogenous condition caused by combinations of hemodynamic and neurohormonal abnorma-lities. These abnormalities are typically dynamic, leading to wide fluctuations over time in cardiac function, volume status, and physical functioning in individual patients. HF signs and symptoms initially occur when the heart is unable to produce sufficient cardiac output to perfuse body tissues and meet metabolic demands. Initially beneficial compensatory neurohormonal and parahormonal mechanisms can eventually lead to progression and perpetuation of the HF syndrome. Figure shows the pathophysiology of heart failure. The common risk factors or conditions that lead to hemodynamic abnormalities at the cardiac level include myocardial ischemia and infarction, hypertension, aging, obesity, diabetes, valvular heart disease, congenital heart defects, and alcoholism. Additional risk factors for coronary artery disease (hyperlipidemia, smoking, homocysteine) because they lead to eventual myocardial injury are also indirect risk factors for heart failure. Most patients have multiple risk factors for HF.
These risk factors either through myocardial injury or persistent alteration of cardiac hemodynamic forces lead to impaired LV function. In a patient with signs and symptoms of HF, left ventricular dysfunction can be present during systole, diastole, or both. In patients with systolic dysfunction the reduction in the transmural forces across the left ventricle and possibly reduced cardiac output detected by the kidneys lead to activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS). Heightened activity of these two neurohormonal systems leads to further myocardial toxicity, peripheral vasoconstriction, and renal salt and water retention. The activation of these systems leads to further worsening of LV function and progressive remodeling of the heart . The principal manifestation of cardiac remodeling is a change in the shape of the left ventricle such that the chamber dilates, hypertrophies, and becomes more spherical. Initial dilitation of the ventricle creates a mechanical advantage for maintaining stroke volume and cardiac output. Eventually, changes in chamber size increase the mechanical stress on the walls of the heart, increase myocardial oxygen demand, and further reduce ventricular performance. If these processes proceed unimpeded, the heart continues to dilate to the "big baggy heart" seen in end-stage systolic dysfunction HF. Approximately 40% of primary care HF patients have normal LV systolic function. The most common underlying abnormality in HF patients with normal systolic function is LV diastolic dysfunction. Reduced diastolic capacity and impaired ventricular relaxation causes a decrease in ventricular filling rate and volume during diastole and elevated end-diastolic pressure. Persistent activation of neurohormonal mechanisms also plays a role in fluid retention and HF signs and symptoms for patients with isolated diastolic dysfunction. Common causes of HF with normal systolic function include Inaccurate diagnosis of HF (e.g., chronic obstructive pulmonary disease [COPD]) Inaccurate measurement of LV ejection fraction (LVEF) LV systolic function overestimated by LVEF (e.g., mitral regurgitation) Episodic LV systolic dysfunction, normal at the time of evaluation (severe hypertension, ischemia, tachycardia, infection, volume overload, spontaneous variability of EF)