Guyton and Hall Physiology Chapter 22 - Cardiac Failure.PDF

CHAPTER 22 UNIT IV Cardiac Failure One of the most important ailmen...

CHAPTER 22 UNIT IV Cardiac Failure One of the most important ailments treated by the phy- the heart from the body is dammed up in the right atrium. sician is cardiac failure (heart failure). This ailment can This low cardiac output is still sufficient to sustain life for result from any heart condition that reduces the ability perhaps a few hours, but it is likely to be associated with of the heart to pump enough blood to meet the body’s fainting. Fortunately, this acute stage usually lasts for only needs. The cause is often decreased contractility of the a few seconds because sympathetic nervous reflexes occur myocardium resulting from diminished coronary blood almost immediately and compensate, to a great extent, for flow. However, cardiac failure can also be caused by dam- the damaged heart, as follows. aged heart valves, external pressure around the heart, vitamin B deficiency, primary cardiac muscle disease, or Compensation for Acute Cardiac Failure by any other abnormality that makes the heart a hypoeffec- Sympathetic Nervous Reflexes. When the cardiac out- tive pump. put falls precariously low, many of the circulatory reflexes In this chapter, we mainly discuss cardiac failure caused discussed in Chapter 18 are rapidly activated. The best by ischemic heart disease resulting from partial blockage known of these is the baroreceptor reflex, which is acti- of the coronary blood vessels, which is the most common vated by diminished arterial pressure. The chemoreceptor cause of heart failure. In Chapter 23, we discuss valvular reflex, the central nervous system ischemic response, and and congenital heart disease. even reflexes that originate in the damaged heart also likely contribute to activation of the sympathetic nerv- ous system. The sympathetics therefore become strongly CIRCULATORY DYNAMICS IN CARDIAC stimulated within a few seconds, and the parasympathetic FAILURE nervous signals to the heart become inhibited at the same time. ACUTE EFFECTS OF MODERATE CARDIAC Strong sympathetic stimulation has major effects on FAILURE the heart and peripheral vasculature. If all the ventricu- If a heart suddenly becomes severely damaged, such lar musculature is diffusely damaged but is still func- as by myocardial infarction, the pumping ability of the tional, sympathetic stimulation strengthens this damaged heart is immediately depressed. As a result, two main musculature. If part of the muscle is nonfunctional, and effects occur: (1) reduced cardiac output; and (2) dam- part of it is still normal, the normal muscle is strongly ming of blood in the veins, resulting in increased venous stimulated by sympathetic stimulation, in this way par- pressure. tially compensating for the nonfunctional muscle. Thus, The progressive changes in heart pumping effective- the heart becomes a stronger pump as a result of sympa- ness at different times after an acute myocardial infarc- thetic stimulation. This effect is illustrated in Figure 22-­1, tion are shown graphically in Figure 22-­1. The top curve which shows about a twofold elevation of the very low of this figure shows a normal cardiac output curve. Point cardiac output curve after sympathetic compensation. A on this curve is the normal operating point, showing a Sympathetic stimulation also increases venous return normal cardiac output under resting conditions of 5 L/ because it increases the tone of most of the blood vessels min and a right atrial pressure of 0 mm Hg. of the circulation, especially the veins, raising the mean Immediately after the heart becomes damaged, the systemic filling pressure to 12 to 14 mm Hg, almost 100% cardiac output curve becomes greatly depressed, falling to above normal. As discussed in Chapter 20, this increased the lowest curve at the bottom of the graph. Within a few filling pressure greatly increases the tendency for blood seconds, a new circulatory state is established at point B, to flow from the veins back into the heart. Therefore, the illustrating that the cardiac output has fallen to 2 L/min, damaged heart becomes primed with more inflowing about two-­fifths normal, whereas the right atrial pressure blood than usual, and the right atrial pressure rises still has risen to +4 mm Hg because venous blood returning to further, which helps the heart pump still larger quantities 271 UNIT IV The Circulation Normal heart Moderate Fluid Retention in Cardiac Failure Can Be Partially recovered heart Beneficial. Many cardiologists have considered fluid Damaged heart + sympathetic stimulation retention always to have a detrimental effect in cardiac 15 Acutely damaged heart failure. However, a moderate increase in body fluid and blood volume is an important factor in helping to com- pensate for the diminished pumping ability of the heart Cardiac output (L/min) by increasing the venous return. The increased blood vol- 10 ume increases venous return in two ways. First, it increas- es the mean systemic filling pressure, which increases the pressure gradient for causing venous flow of blood toward A D the heart. Second, it distends the veins, which reduces the 5 venous resistance and allows even more ease of flow of C blood to the heart. If the heart is not damaged too much, this increased B venous return can almost fully compensate for the heart’s 0 −4 −2 0 +2 +4 +6 +8 +10 +12 +14 diminished pumping ability—enough so that even when Right atrial pressure (mm Hg) the heart’s pumping ability is reduced to as low as 40% to 50% of normal, the increased venous return can often Figure 22-­1 Progressive changes in the cardiac output curve after acute myocardial infarction. Both the cardiac output and right atrial cause nearly normal cardiac output as long as the person pressure change progressively from point A to point D (illustrated by remains in a quiet resting state. the black line) over a period of seconds, minutes, days, and weeks. When the heart’s pumping capability is reduced fur- ther, blood flow to the kidneys finally becomes too low of blood. Thus, in Figure 22-­1, the new circulatory state for the kidneys to excrete enough salt and water to equal is depicted by point C, showing a cardiac output of 4.2 L/ salt and water intake. Therefore, fluid retention begins min and a right atrial pressure of 5 mm Hg. and continues indefinitely unless major therapeutic pro- The sympathetic reflexes become maximally devel- cedures are used to prevent this outcome. Furthermore, oped in about 30 seconds. Therefore, a person who has because the heart is already pumping at its maximum a sudden, moderate heart attack might experience noth- capacity, this excess fluid no longer has a beneficial effect ing more than cardiac pain and a few seconds of fainting. on the circulation. Instead, the fluid retention increases Shortly thereafter, with the aid of the sympathetic reflex the workload on the already damaged heart, and severe compensations, the cardiac output may return to a level edema develops throughout the body, which can be very adequate to sustain the person if he or she remains quiet, detrimental and can lead to death. although the pain might persist. Detrimental Effects of Excess Fluid Retention in Severe Cardiac Failure. In contrast to the beneficial CHRONIC STAGE OF FAILURE—FLUID effects of moderate fluid retention in cardiac failure, in RETENTION AND COMPENSATED severe cardiac failure, extreme excesses of fluid can have CARDIAC OUTPUT serious physiologic consequences. These include the fol- After the first few minutes of an acute heart attack, a lowing: (1) increasing the workload on the damaged heart; prolonged semichronic state begins, characterized (2) overstretching of the heart, which further weakens the mainly by two events: (1) retention of fluid by the kid- heart; (3) filtration of fluid into the lungs, causing pulmo- neys; and (2) varying degrees of recovery of the heart nary edema and consequent deoxygenation of the blood; over a period of weeks to months, as illustrated by the and (4) development of extensive edema in most parts of light green curve in Figure 22-­1. This topic was also the body. These detrimental effects of excessive fluid are discussed in Chapter 21. discussed in later sections of this chapter. Renal Retention of Fluid and Increase in Recovery of the Heart After Myocardial Blood Volume Occur for Hours to Days Infarction A low cardiac output has a profound effect on renal After a heart becomes suddenly damaged as a result of function, sometimes causing anuria when the cardiac myocardial infarction, the natural reparative processes of output falls to 50% to 60% of normal. In general, the the body begin to help restore normal cardiac function. urine output remains below normal as long as the car- For example, a new collateral blood supply begins to pen- diac output and arterial pressure remain significantly etrate the peripheral portions of the infarcted area of the less than normal; urine output usually does not return heart, often causing some of the heart muscle in the fringe all the way to normal after an acute heart attack until areas to become functional again. Also, the undamaged the cardiac output and arterial pressure rise almost to portion of the heart musculature hypertrophies, offset- normal levels. ting some of the cardiac damage. 272  Chapter 22 Cardiac Failure The degree of recovery, which depends on the type Critical cardiac output level and severity of cardiac damage, varies from no recovery for normal fluid balance to almost complete recovery. After an acute myocardial Cardiac output infarction, the heart ordinarily recovers rapidly during the (L/min) 5.0 first few days and weeks and achieves most of its final state 2.5 B C D E UNIT IV of recovery within 5 to 7 weeks, although mild degrees of A F additional recovery can continue for months. 0 −4 0 +4 +8 +12 +16 Cardiac Output Curve After Partial Recovery. Figure Right atrial pressure (mm Hg) 22-­1 shows function of the partially recovered heart a Figure 22-­2 Greatly depressed cardiac output that indicates decom- week or so after an acute myocardial infarction. By this pensated heart disease. Progressive fluid retention raises the right time, considerable fluid has been retained in the body, atrial pressure over a period of days, and the cardiac output pro- and the tendency for venous return has increased mark- gresses from point A to point F until death occurs. edly as well; therefore, the right atrial pressure has risen even more. As a result, the state of the circulation is now Compensated Heart Failure. Note especially in Figure changed from point C to point D, which shows a normal 22-­1 that the maximum pumping ability of the partly re- cardiac output of 5 L/min but right atrial pressure in- covered heart, as depicted by the plateau level of the light creased to 6 mm Hg. green curve, is still depressed to less than half-­normal. Because the cardiac output has returned to normal, This demonstrates that an increase in right atrial pressure renal output of fluid also returns to normal, and no further can maintain the cardiac output at a normal level, despite fluid retention occurs, except that the retention of fluid continued weakness of the heart. Thus, many people, es- that has already occurred continues to maintain moderate pecially older adults, have normal resting cardiac outputs excesses of fluid. Therefore, except for the high right atrial but mildly to moderately elevated right atrial pressures pressure represented by point D in this figure, the person because of various degrees of compensated heart failure. now has essentially normal cardiovascular dynamics as They may not know that they have cardiac damage be- long as he or she remains at rest. cause the damage often has occurred a little at a time, and If the heart recovers to a significant extent, and if ade- the compensation has occurred concurrently with the pro- quate fluid volume has been retained, the cardiac output gressive stages of damage. increases toward normal and sympathetic stimulation When a person is in a state of compensated heart fail- gradually abates toward normal. As the heart recovers, ure, any attempt to perform heavy exercise usually causes the fast pulse rate, cold skin, and pallor resulting from immediate return of the symptoms of acute heart fail- sympathetic stimulation in the acute stage of cardiac fail- ure because the heart is not able to increase its pumping ure gradually disappear. capacity to the levels required for the exercise. Therefore, it is said that the cardiac reserve is reduced in compen- sated heart failure. This concept of cardiac reserve is dis- cussed later in the chapter. SUMMARY OF CHANGES AFTER ACUTE CARDIAC FAILURE—COMPENSATED HEART FAILURE DYNAMICS OF SEVERE CARDIAC To summarize the events discussed in the past few sec- FAILURE—DECOMPENSATED HEART tions describing the dynamics of circulatory changes after FAILURE an acute, moderate heart attack, we can divide the stages into the following: (1) the instantaneous effect of the car- If the heart becomes severely damaged, no amount of diac damage; (2) compensation by the sympathetic nervous compensation by sympathetic nervous reflexes or fluid system, which occurs mainly within the first 30 to 60 sec- retention can make the excessively weakened heart onds; and (3) chronic compensations resulting from par- pump a normal cardiac output. As a consequence, the tial heart recovery and renal retention of fluid. All these cardiac output cannot rise high enough to make the kid- changes are shown graphically by the black line in Figure neys excrete normal quantities of fluid. Therefore, fluid 22-­1. The progression of this line shows the normal state of continues to be retained, the person develops more and the circulation (point A), the state a few seconds after the more edema, and this state of events eventually leads to heart attack but before sympathetic reflexes have occurred death. This condition is called decompensated heart fail- (point B), the rise in cardiac output toward normal caused ure. Thus, a major cause of decompensated heart failure is by sympathetic stimulation (point C), and final return of failure of the heart to pump sufficient blood to make the the cardiac output to almost normal after several days to kidneys excrete the necessary amounts of fluid every day. several weeks of partial cardiac recovery and fluid reten- tion (point D). This final state is called compensated heart Graphic Analysis of Decompensated Heart Failure. failure. Figure 22-­2 shows greatly depressed cardiac output at 273 UNIT IV The Circulation different times (points A to F) after the heart has be- Thus, one can see from this analysis that failure of the come severely weakened. Point A on this curve repre- cardiac output (and arterial pressure) to rise to the criti- sents the approximate state of the circulation before any cal level required for normal renal function results in the compensation has occurred, and point B represents the following: (1) progressive retention of more and more state a few minutes later, after sympathetic stimulation fluid; (2) progressive elevation of the mean systemic filling has compensated as much as it can but before fluid re- pressure; and (3) progressive elevation of the right atrial tention has begun. At this time, the cardiac output has pressure until, finally, the heart is so overstretched or so risen to 4 L/min and the right atrial pressure has risen edematous that it cannot pump even moderate quantities to 5 mm Hg. The person appears to be in reasonably of blood and, therefore, fails completely. Clinically, one good condition, but this state will not remain stable be- detects this serious condition of decompensation princi- cause the cardiac output has not risen high enough to pally by the progressing edema, especially edema of the cause adequate kidney excretion of fluid; therefore, flu- lungs, which leads to bubbling rales (a crackling sound) in id retention continues and can eventually be the cause the lungs and to dyspnea (air hunger). Lack of appropriate of death. These events can be explained quantitatively therapy at this stage rapidly leads to death. in the following way. Note the straight line in Figure 22-­2, at a cardiac Treatment of Decompensation. The decompensa- output level of 5 L/min. This level is approximately the tion process can often be stopped by the following: (1) critical cardiac output level that is required in the average strengthening the heart in any one of several ways, espe- adult person to make the kidneys reestablish normal fluid cially by administering a cardiotonic drug, such as digi- balance—that is, for the output of salt and water to be as talis, so that the heart becomes strong enough to pump high as the intake of these substances. At cardiac outputs adequate quantities of blood required to make the kid- below this level, the fluid-­retaining mechanisms discussed neys function normally again; or (2) administering diu- in the earlier section remain in play, and the body fluid retic drugs to increase kidney excretion while at the same volume increases progressively. Because of this progres- time reducing water and salt intake, which results in a bal- sive increase in fluid volume, the mean systemic filling ance between fluid intake and output, despite low cardiac pressure of the circulation continues to rise, which forces output. progressively increasing quantities of blood from the per- Both methods stop the decompensation process by re-­ son’s peripheral veins into the right atrium, thus increas- establishing normal fluid balance so that at least as much ing the right atrial pressure. After 1 day or so, the state of fluid leaves the body as enters it. the circulation changes in Figure 22-­2 from point B to point C, with the right atrial pressure rising to 7 mm Hg Mechanism of Action of Cardiotonic Drugs. Cardiot- and the cardiac output rising to 4.2 L/min. Note again that onic drugs, such as digitalis, when administered to a per- the cardiac output is still not high enough to cause nor- son with a healthy heart, have little effect on increasing mal renal output of fluid; therefore, fluid continues to be the contractile strength of the cardiac muscle. However, retained. After another day or so, the right atrial pressure when administered to someone with a chronically fail- rises to 9 mm Hg, and the circulatory state becomes that ing heart, the same drugs can sometimes increase the depicted by point D. Still, the cardiac output is not enough strength of the failing myocardium by as much as 50% to to establish normal fluid balance. 100%. Therefore, they are one of the mainstays of therapy After another few days of fluid retention, the right atrial in persons with chronic heart failure. pressure has risen further but, by now, cardiac function Digitalis and other cardiotonic glycosides are believed is beginning to decline toward a lower level. This decline to strengthen heart contractions by increasing the quan- is caused by overstretch of the heart, edema of the heart tity of calcium ions in muscle fibers. This effect is likely muscle, and other factors that diminish the heart’s pump- due to inhibition of sodium-­ potassium adenosine tri- ing performance. It is now clear that further retention of phosphatase in cardiac cell membranes. Inhibition of fluid will be more detrimental than beneficial to the cir- the sodium-­potassium pump increases the intracellular culation. Yet, the cardiac output still is not high enough sodium concentration and slows the sodium-­ calcium to bring about normal renal function, so fluid retention exchange pump, which extrudes calcium from the cell not only continues but accelerates because of the falling in exchange for sodium. Because the sodium-­ calcium cardiac output (and the falling arterial pressure that also exchange pump relies on a high sodium gradient across occurs). Consequently, within a few days, the state of the the cell membrane, accumulation of sodium inside the circulation has reached point F on the curve, with the car- cell reduces its activity. diac output now less than 2.5 L/min and the right atrial In the failing heart muscle, the sarcoplasmic reticu- pressure 16 mm Hg. This state has approached or reached lum fails to accumulate normal quantities of calcium and, incompatibility with life, and the patient will die unless therefore, cannot release enough calcium ions into the this chain of events can be reversed. This state of heart free fluid compartment of the muscle fibers to cause full failure in which the failure continues to worsen is called contraction of the muscle. The effect of digitalis to depress decompensated heart failure. the sodium-­calcium exchange pump and raise calcium 274  Chapter 22 Cardiac Failure ion concentration in cardiac muscle provides the extra sively more damaged when its coronary blood supply is re- calcium needed to increase the muscle contractile force. duced during the course of the shock. That is, the low arte- Therefore, it is usually beneficial to depress the calcium rial pressure that occurs during shock reduces the coronary pumping mechanism by a moderate amount using digi- blood supply even more. This reduction further weakens talis, allowing the muscle fiber intracellular calcium level the heart, which makes the arterial pressure fall further, UNIT IV to rise slightly. which makes the shock progressively worse; the process eventually becomes a vicious cycle of cardiac deterioration. In cardiogenic shock caused by myocardial infarction, this UNILATERAL LEFT HEART FAILURE problem is greatly compounded by already existing coro- Thus far we have considered failure of the heart as a nary vessel blockage. For example, in a healthy heart, the whole. Yet, in a large number of patients, especially those arterial pressure usually must be reduced below about 45 with early acute heart failure, left-­sided failure predomi- mm Hg before cardiac deterioration sets in. However, in nates over right-­sided failure and, in rare cases, the right a heart that already has a blocked major coronary vessel, side fails without significant failure of the left side. deterioration begins when the coronary arterial pressure When the left side of the heart fails without concomi- falls below 80 to 90 mm Hg. In other words, even a small tant failure of the right side, blood continues to be pumped decrease in arterial pressure can now set off a vicious cycle into the lungs with usual right heart vigor, whereas it is of cardiac deterioration. For this reason, in treating myo- not pumped adequately out of the lungs by the left heart cardial infarction, it is extremely important to prevent even into the systemic circulation. As a result, the mean pul- short periods of hypotension. monary filling pressure rises because of the shift of large volumes of blood from the systemic circulation into the Physiology of Cardiogenic Shock Treatment. Often, a pulmonary circulation. patient dies of cardiogenic shock before the various com- As the volume of blood in the lungs increases, the pensatory processes can return the cardiac output (and pulmonary capillary pressure increases and, if this pres- arterial pressure) to a life-­ sustaining level. Therefore, sure rises above a value approximately equal to the colloid treatment of this condition is one of the most important osmotic pressure of the plasma—about 28 mm Hg—fluid challenges in the management of acute heart attacks. begins to filter out of the capillaries into the lung inter- Digitalis is often administered immediately to strengthen stitial spaces and alveoli, resulting in pulmonary edema. the heart if the ventricular muscle shows signs of deteriora- Thus, the most important problems of left heart fail- tion. Also, infusion of whole blood, plasma, or a blood pres- ure include pulmonary vascular congestion and pulmo- sure–raising drug is used to sustain the arterial pressure. If nary edema. In severe, acute, left heart failure, pulmonary the arterial pressure can be elevated to a high enough level, edema occasionally occurs so rapidly that it can cause the coronary blood flow often will increase enough to pre- death by suffocation in 20 to 30 minutes, discussed later vent the vicious cycle of deterioration. This process allows in this chapter. enough time for appropriate compensatory mechanisms in the circulatory system to correct the shock. Some success has also been achieved in saving the lives LOW-­OUTPUT CARDIAC FAILURE— of patients in cardiogenic shock by using one of the fol- CARDIOGENIC SHOCK lowing procedures: (1) surgically removing the clot in the In many cases after acute heart attacks, and often after coronary artery, often in combination with a coronary prolonged periods of slow progressive cardiac deteriora- bypass graft; or (2) catheterizing the blocked coronary tion, the heart becomes incapable of pumping even the artery and infusing streptokinase or tissue-­type plasmino- minimal amount of blood flow required to keep the body gen activator enzymes that causes dissolution of the clot. alive. Consequently, the body tissues begin to suffer and The results are occasionally astounding when one of these even to deteriorate, often leading to death within a few procedures is instituted within the first hour of cardio- hours to a few days. The picture, then, is one of circulatory genic shock but are of little, if any, benefit after 3 hours. shock, as explained in Chapter 24. Even the cardiovascu- lar system suffers from lack of nutrition and deteriorates, along with the remainder of the body, thus hastening EDEMA IN PATIENTS WITH CARDIAC death. This circulatory shock syndrome caused by inade- FAILURE quate cardiac pumping is called cardiogenic shock or sim- ply cardiac shock. Once cardiogenic shock develops, the Acute Cardiac Failure Does Not Cause Immediate survival rate is often less than 30%, even with appropriate Peripheral Edema. Acute left heart failure can cause medical care. rapid congestion of the lungs, with the development of pulmonary edema and even death within minutes to Vicious Cycle of Cardiac Deterioration in Cardiogenic hours. However, left or right heart failure is slow to cause Shock. The discussion of circulatory shock in Chapter 24 peripheral edema. This situation can best be explained emphasizes the tendency for the heart to become progres- by referring to Figure 22-­3. When a previously healthy 275 UNIT IV The Circulation Mean aortic pressure urine output. A fall in the cardiac output to about Capillary pressure half-­normal can result in almost complete anuria. 100 Right atrial pressure 2. Activation of renin-­angiotensin system and in- creased reabsorption of water and salt by renal 80 tubules. The reduced blood flow to the kidneys Pressure (mm Hg) causes a marked increase in renin secretion by the 60 kidneys, which in turn increases the formation of angiotensin II, as described in Chapter 19. Angio- 40 13 mm Hg tensin II, in turn, has a direct effect on the arteri- oles of the kidneys to decrease blood flow through 20 the kidneys further, which reduces the pressure in 0 the peritubular capillaries surrounding the renal tu- Normal 1/2 Normal Zero bules, promoting greatly increased reabsorption of Cardiac output water and salt from the tubules. Angiotensin II also Figure 22-­3 Progressive changes in mean aortic pressure, peripheral acts directly on the renal tubular epithelial cells to tissue capillary pressure, and right atrial pressure as the cardiac out- stimulate reabsorption of salt and water. Therefore, put falls from normal to zero. loss of water and salt into the urine decreases great- ly, and large quantities of salt and water accumulate in the blood and interstitial fluids throughout the heart acutely fails as a pump, the aortic pressure falls, and body. the right atrial pressure rises. As the cardiac output ap- 3. Increased aldosterone secretion. In the chronic proaches zero, these two pressures approach each other stage of heart failure, large quantities of aldoster- at an equilibrium value of about 13 mm Hg. Capillary one are secreted by the adrenal cortex. This secre- pressure also falls from its normal value of 17 mm Hg to tion results mainly from the effect of angiotensin the new equilibrium pressure of 13 mm Hg. Thus, severe II to stimulate aldosterone secretion by the adrenal acute cardiac failure often causes a fall rather than a rise cortex. However, some of the increase in aldoster- in peripheral capillary pressure. Therefore, animal experi- one secretion often results from increased plasma ments, as well as experience in humans, have shown that potassium concentration. Excess potassium is one acute cardiac failure almost never causes immediate de- of the most powerful stimuli known for aldoster- velopment of peripheral edema. one secretion, and the potassium concentration rises in response to reduced renal function in those with cardiac failure. The elevated aldosterone level LONG-­TERM FLUID RETENTION BY THE further increases reabsorption of sodium from the KIDNEYS CAUSES PERIPHERAL EDEMA IN renal tubules, which in turn leads to a secondary PERSISTING HEART FAILURE increase in water reabsorption, as discussed in ­ After the first day or so of overall heart failure or right Chapter 28. ventricular heart failure, peripheral edema begins to 4. Increased antidiuretic hormone secretion. In occur, principally because of fluid retention by the kidneys. advanced heart failure, increased secretion of anti- The retention of fluid increases the mean systemic filling diuretic hormone (ADH) may contribute to excessive pressure, resulting in an increased tendency for blood to water reabsorption by the renal tubules. As discussed return to the heart. This further elevates the right atrial in Chapters 28 and 29, ADH is secreted by the hy- pressure and returns the arterial pressure back toward pothalamic–posterior pituitary gland system in re- normal. Therefore, the capillary pressure now also rises sponse to increased extracellular fluid osmolarity, as markedly, thus causing loss of fluid into the tissues and well as nonosmotic stimuli from low-­pressure (e.g., the development of severe edema. left atrial) and high-­pressure (e.g., carotid sinus) ba- Reduced renal output of urine during cardiac failure roreceptors. In severe heart failure, the nonosmotic has several known causes. effects of reductions in cardiac output and arterial 1. Decreased glomerular filtration rate. A decrease pressure may predominate to stimulate secretion of in cardiac output has a tendency to reduce the glo- ADH, which in turn causes excess water retention merular pressure in the kidneys because of the fol- and hyponatremia (low plasma sodium concentra- lowing: (a) reduced arterial pressure; and (b) intense tion). Inappropriately high levels of ADH and hy- sympathetic constriction of the afferent arterioles of ponatremia are predictors for worsening outcomes the kidney. As a consequence, except in the mildest in patients with heart failure. degrees of heart failure, the glomerular filtration rate 5. Activation of sympathetic nervous system. As is reduced. It is clear from the discussion of kidney discussed previously, heart failure causes marked function in Chapters 27 through 30 that a decrease activation of the sympathetic nervous system, in glomerular filtration often markedly decreases which in turn has several effects that lead to salt 276  Chapter 22 Cardiac Failure and water retention by the kidneys: (a) constric- 5. The peripheral vasodilation further increases ve- tion of renal afferent arterioles, which reduces the nous return of blood from the peripheral circula- glomerular filtration rate; (b) stimulation of renal tion. tubular reabsorption of salt and water by activation 6. The increased venous return further increases dam- of alpha-­adrenergic receptors on tubular epithelial ming of the blood in the lungs, leading to, for ex- UNIT IV cells; (c) stimulation of renin release and angioten- ample, still more transudation of fluid, more arte- sin II formation, which increases renal tubular reab- rial oxygen desaturation, and more venous return. sorption; and (d) stimulation of ADH release from Thus, a vicious cycle has been established. the posterior pituitary, which then increases water Once this vicious cycle has proceeded beyond a reabsorption by the renal tubules. These effects of certain critical point, it will continue until the patient sympathetic stimulation are discussed in Chapters dies, unless successful therapeutic measures are initi- 27 and 28. ated within minutes. The types of measures that can reverse the process and save the patient’s life include the Role of Natriuretic Peptides in Delaying Onset of following: Cardiac Decompensation. Natriuretic peptides are hor- 1. Putting tourniquets on both arms and legs to se- mones released by the heart when it becomes stretched. quester much of the blood in the veins and, there- Atrial natriuretic peptide (ANP) is released by the atrial fore, decrease the workload on the left side of the heart walls, and brain natriuretic peptide (BNP) is released by the ventricular walls. Because heart failure almost always 2. Administering a rapidly acting diuretic, such as increases the atrial and ventricular pressures that stretch furosemide, to cause rapid loss of fluid from the body the walls of these chambers, circulating levels of ANP and BNP in the blood may increase severalfold in severe heart 3. Giving the patient pure oxygen to breathe to reverse the blood oxygen desaturation, heart deterioration, failure. These natriuretic peptides, in turn, have a direct effect on the kidneys to increase their excretion of salt and peripheral vasodilation and water greatly. Therefore, the natriuretic peptides play 4. Administering a rapidly acting cardiotonic drug, such as digitalis, to strengthen the heart a natural role to help prevent extreme congestive symp- toms during cardiac failure. Because the half-­life of BNP This vicious cycle of acute pulmonary edema can pro- is significantly longer than that of ANP and can be easily ceed so rapidly that death can occur in 20 to 60 minutes. Therefore, any procedure that is to be successful must be measured in the bloodstream, it is often used to diagnose heart failure or to monitor volume status in patients with instituted immediately. established heart failure. The renal effects of ANP are dis- cussed in Chapters 28 and 30. CARDIAC RESERVE The maximum percentage that the cardiac output can Acute Pulmonary Edema in Late-­Stage increase above normal is called the cardiac reserve. Thus, Heart Failure—Another Lethal Vicious in the healthy young adult, the cardiac reserve is 300% to Cycle 400%. In athletically trained persons, it is 500% to 600% or A frequent cause of death is acute pulmonary edema in more. However, in persons with severe heart failure, there patients who have already had heart failure for a long is no cardiac reserve. As an example of normal reserve, time. When acute pulmonary edema occurs in a person the cardiac output of a healthy young adult during vigor- without new cardiac damage, it usually is set off by some ous exercise can rise to about five times normal, which temporary overload of the heart, such as that which might is an increase above normal of 400%—that is, a cardiac result from a bout of heavy exercise, an emotional experi- reserve of 400%. ence, or even a severe cold. The acute pulmonary edema is Any factor that prevents the heart from pumping blood believed to result from the following vicious cycle: satisfactorily will decrease the cardiac reserve. A decrease 1. A temporarily increased load on the already weak in cardiac reserve can result from disorders such as isch- left ventricle initiates the vicious cycle. Because of emic heart disease, primary myocardial disease, vitamin limited pumping capacity of the left heart, blood deficiency that affects cardiac muscle, physical damage to begins to dam up in the lungs. the myocardium, valvular heart disease, and other factors, 2. The increased blood in the lungs elevates the pul- some of which are shown in Figure 22-­4. monary capillary pressure, and a small amount of fluid begins to transude into the lung tissues and Diagnosis of Low Cardiac Reserve—Exercise Test. alveoli. As long as persons with low cardiac reserve remain in 3. The increased fluid in the lungs diminishes the a state of rest, they usually will not experience major degree of oxygenation of the blood. symptoms of heart disease. However, a diagnosis of low 4. The decreased oxygen in the blood further weakens cardiac reserve usually can be made by requiring the the heart and also causes peripheral vasodilation. person to exercise on a treadmill or by walking up and 277 UNIT IV The Circulation Athlete 15 venous return (L/min) 600 Normal Cardiac output and Cardiac reserve (%) 500 10 Normal 400 Mild valvular A D 5 C 300 Moderate disease coronary 200 disease Diphtheria B 0 Severe Severe −4 −2 0 2 4 6 8 10 12 14 100 coronary valvular Right atrial pressure (mm Hg) thrombosis disease Normal 0 Figure 22-­5 Progressive changes in cardiac output, venous return, operation and right atrial pressure during different stages of cardiac failure. Figure 22-­4 Cardiac reserve in different conditions, showing less than zero reserve for two of the conditions. curves cross. Therefore, the normal state of the circula- tion is a cardiac output and venous return of 5 L/min and down steps, either of which requires greatly increased a right atrial pressure of 0 mm Hg. cardiac output. The increased load on the heart rapidly uses up the small amount of reserve that is available, and Acute Heart Attack Reduces Cardiac Output Curve. the cardiac output soon fails to rise high enough to sus- During the first few seconds after a moderately severe tain the body’s new level of activity. The acute effects are heart attack, the cardiac output curve falls to the lower- as follows: most blue curve. During these few seconds, the venous 1. Immediate and sometimes extreme shortness of return curve still has not changed because the peripheral breath (dyspnea) resulting from failure of the heart to circulatory system is still operating normally. Therefore, pump sufficient blood to the tissues, thereby causing the new state of the circulation is depicted by point B, tissue ischemia and creating a sensation of air hunger where the new cardiac output curve crosses the normal 2. Extreme muscle fatigue resulting from muscle is- venous return curve. Thus, the right atrial pressure rises chemia, thus limiting the person’s ability to contin- immediately to 4 mm Hg, whereas the cardiac output falls ue with the exercise to 2 L/min. 3. Excessive increase in heart rate because the nerv- ous reflexes to the heart overreact in an attempt to Sympathetic Reflexes Raise Cardiac Output and Venous overcome the inadequate cardiac output Return Curves. Within the next 30 seconds, the sympa- Exercise tests are part of the armamentarium of the thetic reflexes are activated. They raise the cardiac output cardiologist. These tests take the place of cardiac output and venous return curves (brown dashed curves). Sym- measurements that cannot easily be made in most clinical pathetic stimulation can increase the plateau level of the settings. cardiac output curve by as much as 30% to 100%. It can also increase the mean systemic filling pressure (depicted by the point where the venous return curve crosses the QUANTITATIVE GRAPHIC ANALYSIS OF zero venous return axis) by several millimeters of mer- CARDIAC FAILURE cury—in this figure, from a normal value of 7 mm Hg Although it is possible to understand most general prin- up to 10 mm Hg. This increase in mean systemic filling ciples of cardiac failure using mainly qualitative logic, pressure shifts the entire venous return curve to the right as we have done thus far in this chapter, one can grasp and upward. The new cardiac output and venous return the importance of the different factors in cardiac failure curves now equilibrate at point C—that is, at a right atrial in greater depth by using more quantitative approaches. pressure of +5 mm Hg and a cardiac output of 4 L/min. One such approach is the graphic method for analysis of cardiac output regulation introduced in Chapter 20. In Compensation During the Next Few Days Further the rest of this chapter, we will use this graphic technique Increases Cardiac Output and Venous Return Curves. to analyze several aspects of cardiac failure. During the ensuing week, the cardiac output and venous return curves rise further (green dashed curves) because of Graphic Analysis of Acute Heart Failure the following: (1) some recovery of the heart; and (2) renal and Chronic Compensation retention of salt and water, which raises the mean systemic Figure 22-­5 shows cardiac output and venous return filling pressure still further—this time up to +12 mm Hg. curves for different states of the heart and peripheral The two new curves now equilibrate at point D. Thus, the circulation. The two curves passing through point A are cardiac output has now returned to normal. The right atrial (1) the normal cardiac output curve and (2) the normal pressure, however, has risen still further, to +6 mm Hg. Be- venous return curve. As indicated in Chapter 20, there is cause the cardiac output is now normal, renal output is also only one point on each of these two curves at which the normal, so a new state of equilibrated fluid balance has been circulatory system can operate—point A, where the two achieved. The circulatory system will continue to function 278  Chapter 22 Cardiac Failure 15 Cardiac output and venous return (L/min) venous return (L/min) First Cardiac output and day Critical cardiac output Seve level for normal 10 ral d fluid balance ays la ter G 15 H 6th day 8th 5 eart day Critical cardiac dh 4th day ze ailing UNIT IV ta li ely frt E 2nd day output level ig i ver 10 D Se hea Autonomi for normal 0 c co Normal v mp ens fluid balance −4 −2 0 2 4 6 8 10 12 14 16 eno atio us r n Right atrial pressure (mm Hg) 5 etu rn B C D E A F Figure 22-­7 Treatment of decompensated heart disease showing 0 the effect of digitalis in elevating the cardiac output curve, with this −4 −2 0 2 4 6 8 10 12 14 16 in turn causing increased urine output, progressive shift of the venous return curve to the left, and decreased right atrial pressure. Right atrial pressure (mm Hg) Figure 22-­6 Graphic analysis of decompensated heart disease show- ing progressive shift of the venous return curve to the right and in- curve at point C. The cardiac output rises to 4.2 L/min, creasing right atrial pressure as a result of continued fluid retention. and the right atrial pressure rises to 7 mm Hg. During the succeeding days, the cardiac output never at point D and remain stable, with a normal cardiac output rises high enough to re-­establish normal renal function. and an elevated right atrial pressure, until some additional Fluid continues to be retained, the mean systemic fill- extrinsic factor changes the cardiac output curve or venous ing pressure continues to rise, the venous return curve return curve. continues to shift to the right, and the equilibrium point Using this technique for analysis, one can especially between the venous return curve and cardiac output see the importance of moderate fluid retention and how curve also shifts progressively to point D, point E, and it eventually leads to a new stable state of the circula- finally point F. The equilibration process is now on the tion in mild to moderate heart failure. The interrelation- downslope of the cardiac output curve, and thus further ship between mean systemic filling pressure and cardiac fluid retention causes even more severe cardiac edema pumping at various degrees of heart failure can also be and a detrimental effect on cardiac output. The condition seen. accelerates downhill until death occurs. Note that the events described in Figure 22-­5 are the Thus, decompensation results from the fact that the same as those presented in Figure 22-­1, although in a cardiac output curve never rises to the critical level of 5 more quantitative manner. L/min needed to re-­establish the normal renal excretion of fluid required to result in a balance between fluid input Graphic Analysis of Decompensated and output. Cardiac Failure The black cardiac output curve in Figure 22-­6 is the same Treatment of Decompensated Heart Disease With as the curve shown in Figure 22-­2—a greatly depressed Digitalis. Assume that the stage of decompensation has curve that has already reached a degree of recovery as already reached point E in Figure 22-­6, and then proceed much as this heart can achieve. In this figure, we have to the same point E in Figure 22-­7. At this time, digitalis is added venous return curves that occur during successive given to strengthen the heart. This intervention raises the days after the acute fall of the cardiac output curve to this cardiac output curve to the level shown in Figure 22-­7, but low level. At point A, the curve at time zero equates with there is no immediate change in the venous return curve. the normal venous return curve to give a cardiac output Therefore, the new cardiac output curve equates with the of about 3 L/min. However, stimulation of the sympa- venous return curve at point G. The cardiac output is now thetic nervous system, caused by this low cardiac out- 5.7 L/min, a value higher than the critical level of 5 liters put, increases the mean systemic filling pressure within required to make the kidneys excrete normal amounts of 30 seconds from 7 to 10.5 mm Hg. This effect shifts the urine. The increased cardiac output, along with the well-­ venous return curve upward and to the right to produce known diuretic effect of digitalis, permits the kidneys to the curve labeled “autonomic compensation.” Thus, the eliminate some of the excess fluid. new venous return curve equates with the cardiac output The progressive loss of fluid over a period of several curve at point B. The cardiac output has been improved to days reduces mean systemic filling pressure down to a level of 4 L/min but at the expense of an additional rise 11.5 mm Hg, and the new venous return curve becomes in right atrial pressure to 5 mm Hg. the curve labeled “Several days later.” This curve equates The cardiac output of 4 L/min is still too low for the kid- with the cardiac output curve of the digitalized heart neys to function normally. Therefore, fluid continues to be at point H, at an output of 5 L/min and a right atrial retained and the mean systemic filling pressure rises from pressure of 4.6 mm Hg. This cardiac output is precisely 10.5 to almost 13 mm Hg. Now the venous return curve is that required for normal fluid balance. Therefore, no labeled “2nd day” and equilibrates with the cardiac output additional fluid will be lost, and none will be gained. 279 UNIT IV The Circulation Consequently, the circulatory system has now stabilized 25 or, in other words, the decompensation of the heart fail- AV venous return (L/min) ure has been compensated. To state this another way, 20 Cardiac output and fist the final steady-­ state condition of the circulation is Normal ula Normal cardiac defined by the crossing point of three curves—the car- 15 venous output curve return B diac output curve, venous return curve, and the critical curve level for normal fluid balance. The compensatory mech- 10 C anisms automatically stabilize the circulation when all 5 Beriberi three curves cross at the same point. A heart disease 0 HEART FAILURE WITH DIASTOLIC −4 −2 0 2 4 6 8 10 12 14 16 DYSFUNCTION AND NORMAL Right atrial pressure (mm Hg) EJECTION FRACTION Figure 22-­8 Graphic analysis of two types of conditions that can cause high-­output cardiac failure—arteriovenous (AV) fistula and Our discussion thus far has focused mainly on cardiac beriberi heart disease. failure due to decreased contractility of the myocardium following a myocardial infarction or impaired coronary abnormalities of ventricular filling as well as impaired blood flow. However, as discussed earlier in the chapter, contractility and impaired systolic function. Most of the heart failure can occur from any condition that decreases neurohumoral changes in heart failure that have been dis- the heart’s ability to pump enough blood to meet the cussed, including activation of the sympathetic and renin-­ body’s needs. Heart failure associated with impaired angiotensin system, as well as excessive fluid retention by cardiac contractility is often referred to as systolic heart the kidneys, occur regardless of whether there is normal failure or heart failure with reduced ejection fraction or reduced EF. Heart failure is a heterogeneous syndrome, (HFrEF). As discussed in Chapter 9, the ejection fraction rather than a specific disease, and occurs whenever the (EF), often assessed by echocardiography, is the fraction heart is unable to pump enough blood to meet the needs of the end-­diastolic volume of the left ventricle that is of the body. ejected with each contraction. An EF of 0.6 means that Thus, measurements of EF, although useful, do not 60% of the end-­diastolic volume ventricle is pumped with always provide an accurate assessment of cardiac func- each heartbeat. Normal values for EF are considered to be tion. A small thick heart with impaired diastolic filling from 50% to 70%. When the heart muscle is weakened, as may be unable to pump the appropriate stroke volume a result of a myocardial infarction or impaired coronary and cardiac output to meet the body’s needs but could blood flow, the EF is usually reduced, with values below have a normal or elevated EF. This example illustrates the 40% considered to be indicative of HFrEF. limitations of left ventricular EF as a marker of left ven- Heart failure can also be associated with normal EF if tricular function and as a means of categorizing patients the heart muscle becomes thickened and stiff (concentric with heart failure of different causes. hypertrophy), so that filling of the ventricles is impaired, and the ventricles hold a smaller than usual volume of HIGH-­OUTPUT CARDIAC FAILURE blood. Under these conditions, the total amount of blood pumped by the heart may not be enough to meet the Figure 22-­8 provides an analysis of two types of high-­ body’s needs, even though it is pumping with a normal output cardiac failure. One is caused by an arteriove- or even increased EF. This condition is often referred to nous fistula that overloads the heart because of excessive as heart failure with preserved ejection fraction (HFpEF). venous return, even though the pumping capability of During the last 30 to 40 years, a growing proportion the heart is not depressed. The other type is caused by of heart failure patients have presented with HFpEF. Cur- beriberi, in which the venous return is greatly increased rently, over 50% of patients with heart failure patients have because of diminished systemic vascular resistance but, a normal EF. HFpEF occurs more commonly in women at the same time, the pumping capability of the heart is and older adults and especially in those who have obe- depressed. sity, diabetes mellitus, and hypertension, a constellation of disorders often called the cardiometabolic syndrome. Arteriovenous Fistula Increases Venous Return. In these individuals, diastolic dysfunction is characterized The normal black curves of Figure 22-­8 depict the nor- by impairment in the rate of ventricular filling, slowed mal cardiac output and normal venous return curves. relaxation of cardiomyocytes, increased thickness of the These curves equate with each other at point A, which ventricular wall, proliferation of extracellular matrix, and depicts a normal cardiac output of 5 L/min and a normal fibrosis, which contribute to a stiffer left ventricle. right atrial pressure of 0 mm Hg. Although clinicians often classify patients into the Now let us assume that the systemic vascular resistance categories of HFpEF or HFrEF using the EF threshold of (the total peripheral vascular resistance) becomes greatly 50%, most patients with advanced heart failure exhibit decreased because of the opening of a large arteriovenous 280  Chapter 22 Cardiac Failure fistula (a direct opening between a large artery and large Bibliography vein). The venous return curve rotates upward to produce Bahit MC, Kochar A, Granger CB: Post-­myocardial infarction heart the curve labeled “AV fistula.” This venous return curve failure. JACC Heart Fail 6:179, 2018. equates with the normal cardiac output curve at point B, Braunwald E: Cardiomyopathies: an overview. Circ Res 121:711, with a cardiac output of 12.5 L/min and a right atrial pres- 2017. Burke MA, Cook SA, Seidman JG, Seidman CE: Clinical and mecha- UNIT IV sure of 3 mm Hg. 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