Porth's Essentials of Pathophysiology, 4e

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Heart Failure and Circulatory Shock

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preserved ejection fraction (HFpEF) is characterized by a normal or normal EF (>50%) and abnormal diastolic function. 5,18 Persons with a reduced or preserved ejec- tion fraction may be symptomatic or asymptomatic. In order to be diagnosed with heart failure, they must also exhibit signs and symptoms, such as shortness of breath, decreased exercise tolerance, and orthopnea (shortness of breath when lying down). Over the last decade, there has been growing rec- ognition that approximately 50% of adult persons with heart failure have normal or near normal ejection fractions. 18–20 These people are as a group older, more commonly female, and more frequently have systolic hypertension (associated with large artery stiffness) than those with a reduced ejection fraction. Most people with HFpEF do not complain of symptoms at rest, but rather with physical exercise. When present, the signs and symptoms of heart failure are related to which ventricle is dysfunctional: left or right. Reduced versus Preserved Ejection Fraction Heart failure can result frompump failure and an impaired ability to eject blood at a rate commensurate with the met- abolic needs of the tissues (systolic failure), or it can occur because of resistance to filling of one or both ventricles leading to symptoms of congestion (diastolic failure). 17 Reduced Ejection Fraction Heart Failure. Heart fail- ure with a reduced ejection fraction or systolic heart fail- ure is defined as an EF of less than 40%. 21–23 It may result from conditions that impair the contractile performance of the heart (e.g., ischemic heart disease and cardiomy- opathy), produce a volume overload (e.g., valvular insuf- ficiency and anemia), or generate a pressure overload (e.g., hypertension and valvular stenosis) on the heart. Along with the decreased EF and cardiac output that occurs with systolic failure, there is a resultant increase in end-systolic and end-diastolic volumes, ventricular dilation and wall tension, and a rise in ventricular end- diastolic pressure. 17,22 This increased volume, in addition to the normal venous return, leads to an increase in ven- tricular preload. The rise in preload may represent a com- pensatory response to maintain stroke volume through the Frank-Starling mechanism despite a reduction in EF. Increased preload, however, can also lead to an excessive accumulation of blood in the atria and the pulmonary venous system, which causes pulmonary congestion.

Myocardial hypertrophy and remodeling involve a series of complex events at both the molecular and cellular levels. The myocardium is composed of myo- cytes, or muscle cells, and nonmyocytes. The myocytes are the functional units of cardiac muscle. The nonmyo- cytes include cardiac macrophages, fibroblasts, vascular smooth muscle, and endothelial cells. These cells, which are present in the interstitial space, remain capable of an increase in cell number and provide support for the myocytes. The nonmyocytes also determine many of the inappropriate changes that occur during myocar- dial hypertrophy. For example, uncontrolled fibroblast growth is associated with increased synthesis of collagen fibers, myocardial fibrosis, and ventricular wall stiffness. Recent research has focused on understanding the type of hypertrophy that develops in persons with heart fail- ure. At the cellular level, cardiac muscle cells respond to stimuli from stress placed on the ventricular wall by pres- sure and volume overload by initiating several different processes that lead to hypertrophy. These include stimuli that produce a symmetric hypertrophy with a propor- tionate increase in muscle length and width, as occurs in athletes; concentric hypertrophy with an increase in wall thickness, as occurs in hypertension; and eccentric hyper- trophy with a disproportionate increase in muscle length, as occurs in dilated cardiomyopathy 16 (Fig. 20-4). When the primary stimulus for hypertrophy is pressure over- load, the increase in wall stress leads to parallel replication of myofibrils, thickening of the individual myocytes, and concentric hypertrophy. Concentric hypertrophy may pre- serve systolic function for a time, but eventually the work performed by the ventricle exceeds the vascular reserve, predisposing to ischemia. With ventricular volume over- load, the increase in wall stress leads to replication of myofibrils in series, elongation of the cardiac muscle cells, and eccentric hypertrophy. Eccentric hypertrophy leads to a decrease in ventricular wall thickness or thinning of the wall with an increase in diastolic volume and wall tension. Types of Heart Failure Heart failure is commonly classified by the ejection frac- tion (reduced or preserved) or as left-sided or right-sided failure. 17 Heart failure with a reduced ejection fraction (HFrEF) is defined as the inability of the ventricle to eject an adequate cardiac output despite a normal blood pressure with an EF ≤ 40% . 1,18 Heart failure with a

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A C FIGURE 20-4. Different types of myocardial hypertrophy. (A) Normal symmetric hypertrophy with proportionate increases in myocardial wall thickness and length. (B) Concentric hypertrophy with a disproportionate increase in wall thickness. (C) Eccentric hypertrophy with a disproportionate decrease in wall thickness and ventricular dilation.