In 1856, Carl Ludwig first described the intricate interdependence of end-diastolic volume and cardiac stroke volume: “A strong heart that is filled with blood empties itself more or less completely, in other words, changes the extent of the contractile power.” Numerous other scientists and physicians passing through the laboratory of Carl Ludwig advanced the understanding of ventricular hemodynamics until Otto Frank, who studied with Ludwig from 1891 to 1893, defined the relationship of ventricular volume and pressure based on an understanding of the properties of skeletal muscle and described this in the form of a pressure-volume loop. Frank’s interpretation that cardiac muscle function is based on a simple relationship between length and tension proved to be minimalistic. Ernest Henry Starling, in the early 1900s, working primarily with mammalian hearts, added complexity to this idea and published a series of lectures concluding “the rise of venous pressure must be regarded as one of the mechanical means which are operative in enabling the heart to maintain an output corresponding to the blood it receives from the venous system.” Starling noted, however, that many other components are at play in determining the final stroke volume of the heart. Starling also put forth the idea that clinical heart failure occurs when increases in preload, and thus increases in contractility, can no longer compensate for the failing heart muscle. The principles governing the interplay between end-diastolic volume, afterload, contractility, and stroke volume became known as Starling ’ s Law of the Heart and are represented by the Frank-Starling curve. And so was born the concept of ventricular hemodynamics. It was not until the 1960s that the concept of left ventricular pressure-volume relationships was revived, and a better understanding of left ventricular mechanics as displayed by the current pressure-volume loop emerged.
LEFT VENTRICULAR HEMODYNAMICS
To understand the pathophysiology of the various etiologies of heart failure, cardiogenic shock, and the therapies with which they can be treated, it is essential to have a working knowledge of left ventricular hemodynamics. This begins with a thorough understanding of the cardiac cycle ( Fig. 11.1 ). The cardiac cycle consists of two phases: systole and diastole. Left ventricular systole begins when the pressure in the atrium falls below that of the ventricle and the mitral valve closes. A period of isovolumic contraction occurs during which the pressure in the ventricle builds while the volume remains constant until ventricular pressure exceeds aortic pressure, opening the aortic valve. Opening of the aortic valve begins the second phase of systole, ejection, during which systolic pressure continues to rise before falling with the ejection of ventricular volume. Once the left ventricular pressure falls below aortic pressure, the aortic valve closes and diastole begins. As with systole, diastole begins with an isovolumic period during which the ventricle relaxes without change in volume. It is important to note that this relaxation is active and requires energy. Once the pressure in the ventricle falls below that of the atrium, the mitral valve opens and the filling phase of diastole begins. Ventricular filling consists of two phases: passive filling and filling secondary to atrial contraction. Under normal circumstances, the pressure in a normal ventricle rises little in response to increased volume because of continued active relaxation. The cycle completes once the pressure in the ventricle exceeds that in the atrium and the mitral valve closes.
There are numerous factors that contribute to myocardial performance, including afterload, preload, heart rate, myocardial contractility, diastolic parameters, and microvascular function. There are many graphical ways that the interactions between these parameters and the effects on ventricular hemodynamics can be displayed. The Starling curve and the force-tension curve are two easy mechanisms to display the interaction between preload, afterload, contractility, and stroke volume ( Fig. 11.2 ). The Starling curve displays the interaction between the preload and stroke volume. As ventricular volume increases, leading to increased ventricular stretch and active tension, the stroke volume increases if other parameters remain constant. An upward shift in the Starling curve, signifying an increased stroke volume per amount of preload, results from either an increase in contractility or a decrease in afterload. Conversely, a downward shift in the Starling curve signifies a decreased stroke volume per amount of preload and results from either a decrease in contractility or an increase in afterload (see Fig. 11.2A ). The force-tension curve displays the interaction between the afterload and stroke volume. As afterload increases, the stroke volume falls if other parameters remain constant. An upward shift in the force-tension curve, signifying an increase in the stroke volume at a constant afterload, results from either an increase in contractility or an increase in preload. Conversely, a downward shift in the force-tension curve signifies a decrease in the stroke volume at a consistent afterload and results from either a decrease in contractility or a decrease in preload (see Fig. 11.2B ). These two curves in combination can be used to describe the effects of certain actions on ventricular hemodynamics. For example, in Fig. 11.3 , moving from point A to point B on the Starling curve demonstrates a downward shift and a decrease in the stroke volume at a constant preload. This signifies either a decrease in contractility or an increase in afterload. Moving from point A to point B on the force-tension curve clearly demonstrates that the decrease in the stroke volume is due to an increase in afterload. Both contractility and preload are unchanged, as the original force-tension curve has not shifted up or down.
THE PRESSURE-VOLUME LOOP
The information in the cardiac cycle diagram, the Starling curve, and the force-tension curve can be depicted in a single illustration: the pressure-volume loop. This is essentially a plot of the left ventricular pressure versus volume at numerous time points during the cardiac cycle ( Fig. 11.4 ). A basic understanding of the pressure-volume loop can be immensely helpful in understanding the pathophysiology of left ventricular failure, how therapies may alter ventricular hemodynamics, and whether those therapies will be helpful or harmful for certain conditions. There is an enormous amount of information housed within the pressure-volume loop. First, the pressure-volume loop is simply a diagrammatic way of illustrating the cardiac cycle. Point A signifies the end of diastole, when ventricular pressure exceeds atrial pressure, closing the mitral valve. Point A also defines the left ventricular end-diastolic pressure (LVEDP) on the y axis and the end-diastolic volume on the x axis. The distance from point A to point B demonstrates an increase in pressure at a constant volume, the period of isovolumic contraction, and the beginning of systole. Point B signifies the beginning of systolic ejection when the left ventricular pressure exceeds that of the aorta, opening the aortic valve. Ejection occurs from point B to point C and ends once the pressure in the aorta exceeds that in the ventricle, closing the aortic valve. Point C denotes both the end-systolic pressure and the beginning of diastole. The distance from point C to point D demonstrates a decrease in pressure at a constant volume, the period of isovolumic relaxation. At point D, the pressure in the atrium exceeds the ventricle and the mitral valve opens, beginning diastolic filling. Again, it is important to note that increases in diastolic volume result in a comparatively small increase in diastolic pressure in a normal heart. The width of the pressure-volume loop is a representation of stroke volume. Arterial elastance (Ea) is a measure of afterload and is simplistically thought of as the ratio of end-systolic pressure to stroke volume. With acute inferior vena cava occlusion, the effects of sequentially smaller ventricular volumes on ventricular pressure can be diagrammed. This allows for the definition of two relationships: the end-systolic pressure-volume relationship (ESPVR), which is a measure of intrinsic contractility, and the end-diastolic pressure-volume relationship (EDPVR), which is a measure of diastolic stiffness and relaxation ( Fig. 11.5 ). The ESPVR shifts with changes in myocardial contractility, while the EDPVR shifts as the passive relaxation properties of the ventricle change and is also dependent on the left ventricular filling pressures. We can gain additional information from the pressure-volume loop regarding ventricular work ( Fig. 11.6 ). The area inside the pressure-volume loop estimates the stroke work of the ventricle, in practical terms the amount of energy spent for the given stroke volume. The entire area bound by the ESPVR and EDPVR is an estimate of not only the energy spent for ejection but also the potential energy stored and is an estimate of ventricular wall tension and myocardial oxygen demand.
As with the Starling and force-tension curves, the effects of changing various hemodynamic parameters can be diagrammed using a single pressure-volume loop. When afterload (denoted by the end-systolic pressure) and contractility (denoted by the slope of the ESPVR) are unchanged, a decrease in preload (demonstrated by a lower end-diastolic volume) decreases the stroke volume, while an increase in preload (demonstrated by an increase in end-diastolic volume) increases the stroke volume ( Fig. 11.7A and B ). This is anticipated as previously demonstrated with the Starling curve. The pressure-volume loop gives us additional important information, however. In the setting of increased preload, there is not only an increase in stroke volume but also an increase in stroke work (demonstrated by an increase in the area of the pressure-volume loop) and an increase in myocardial wall tension and oxygen consumption (demonstrated by an increase in the area of the pressure-volume relationship). Thus, the increase in stroke volume is at the expense of increased myocardial work and oxygen consumption. Similarly, we can evaluate isolated changes in afterload while maintaining similar preload (left ventricular end-diastolic volume [LVEDV] remains constant) and contractility (the ESPVR slope remains constant) ( Fig. 11.8A and B ). A decrease in afterload (demonstrated by a lower end-systolic pressure) results in an increased stroke volume with mild decreases in myocardial work and oxygen consumption. An increase in afterload (demonstrated by a higher end-systolic pressure) results, conversely, in a decreased stroke volume and an increased myocardial wall tension and oxygen consumption. Finally, changes in contractility can be demonstrated by means of the pressure-volume loop ( Fig. 11.9 ). Changes in contractility are represented on the pressure-volume loop by a change in the slope of the ESPVR. Maintaining similar preload (end-diastolic volume remains constant) and afterload (end-systolic pressure remains constant), an increase in contractility results in an increase in stroke volume, myocardial stroke work, and oxygen consumption. Conversely, a decrease in contractility results in a decrease in stroke volume, myocardial work, and oxygen consumption.
With a basic background of ventricular hemodynamics, it is much easier to understand the pathophysiology of shock and heart failure and lends to a better comprehension of the effects of various therapies on the failing ventricle.
PATHOPHYSIOLOGY OF CARDIOGENIC SHOCK
Cardiogenic shock is defined as persistent hypotension, severe reduction in cardiac index, elevated filling pressures, and reduced end organ perfusion. The inadequacy of end organ perfusion, as evidenced by such things as oliguria, mental status changes, peripheral cyanosis, and cool extremities, defines the clinical presence or absence of shock ( Table 11.1 ). Mortality secondary to cardiogenic shock is high and ranges from 40% to 80% depending on the underlying etiology. Cardiogenic shock can develop from inadequacy of output from the left ventricle, right ventricle, or both. A wide variety of conditions can lead to cardiogenic shock, with acute myocardial infarction and acute decompensated chronic systolic heart failure representing the most common causes ( Box 11.1 ). Both systolic and diastolic mechanisms contribute to shock. An absolute or relative decrease in the left ventricular output leads to hypotension and decreased systemic and coronary perfusion. Increases in LVEDV and LVEDP lead to pulmonary congestion and increased wall stress. This combination results in myocardial oxygen demand that outstrips supply. The hypotension resulting from inadequate output also leads to a compensatory systemic release of catecholamines, with the goal of increasing contractility and peripheral resistance. Unfortunately, the body’s efforts to maintain perfusion to vital organs often result in increased cardiac oxygen demand and work, as well as worsening of organ perfusion secondary to vasoconstriction ( Fig. 11.10 ). Importantly, cardiogenic shock can often be reversed in the early stages, thus recognition and initiation of proper therapy in a timely manner are crucial.
| CRITERIA | MANIFESTATION | PORTENDS POOR PROGNOSIS |
|---|---|---|
| Hypotension | Systolic BP <90 mm Hg for 30 min, unable to reverse with fluids | Mean arterial pressure <60 mm Hg |
| Cardiac index | <2.2 L/min per BSA | <2.0 L/min per BSA |
| Peripheral vasoconstriction | Cool extremities | |
| Renal ischemia | Decreased urine output | <25 mL/h |
| Cerebral ischemia | Mental status changes | Obtunded |
| Normal or high filling pressures | PCWP >18 mm Hg |
Acute Myocardial Infarction
- 1.
Pump failure
- 2.
Right ventricular infarction
- 3.
Ventricular septal rupture
- 4.
Acute mitral regurgitation
- 5.
Free wall rupture
- 6.
Acquired left ventricular outflow tract obstruction
Arrhythmia
- 1.
Bradycardia
- 2.
Tachycardia
Acute Valvular Regurgitation
Aortic regurgitation
Mitral regurgitation
Acute prosthetic valve regurgitation
Obstruction
Decompensated aortic stenosis
Hypertrophic obstructive cardiomyopathy
Acquired left ventricular outflow tract obstruction
Atrial myxoma
Acute prosthetic valve obstruction
Pump Failure
Idiopathic
Myocarditis
Ischemic
Compressive
Tamponade
HEMODYNAMICS OF CARDIOGENIC SHOCK
The differential diagnosis of shock is broad, and the first task of the physician is to determine whether or not the underlying cause of shock is cardiogenic. Clinical suspicion is often confirmed with the aid of right heart and left heart catheterization. The central aortic waveform has several characteristics during shock that can be helpful in its early recognition. The height of the pulse pressure tracing is directly associated with the left ventricular contractility, while the width offers information about stroke volume ( Fig. 11.11 ). The majority of patients with cardiogenic shock display a decreased pulse pressure height and width as both contractility and stroke volume are reduced ( Fig. 11.12 ). However, in cases where the left ventricular function is normal but inadequate, as with acute mitral regurgitation or postmyocardial infarction ventricular septal defect, the pulse pressure height may be normal, but the width reduced, suggesting a marked decrease in forward stroke volume ( Fig. 11.13A ). This narrow “spiked” appearance can herald cardiovascular collapse even in the patient with a “normal” pulse pressure height and apparently adequate systolic pressure (see Fig. 11.13B ).
Right heart catheterization can be used to distinguish cardiogenic shock from other types of shock. Elevation in the right-sided filling pressures, in particular the pulmonary capillary wedge pressure (PCWP), is a consistent feature of cardiogenic shock, but other clues to etiology may be present. For example, acute severe mitral regurgitation often demonstrates a large, pathologic v wave in the PCWP tracing. It is important to remember that some causes of cardiogenic shock may have a low PCWP. For example, shock caused by right-sided heart failure will demonstrate low cardiac output, hypotension, and a normal to low PCWP. Cardiac tamponade in the setting of hypovolemia may also demonstrate low to normal filling pressures, although equalization of diastolic pressures will be present. In combination with aortic pressure measurement, the systemic vascular resistance (SVR) can be calculated. The SVR is high in the presence of cardiogenic shock due to compensatory peripheral vasoconstriction, with the exception of the end stages of shock when acidosis may lead to profound vasodilation.
The SVR is easily calculated using the following formula:
Multiplying the SVR by 80 converts to resistance units, dynes per s/cm 5 . This can be indexed to body size by multiplying by body surface area:
where SVRI is the SVR indexed to body size.
The normal SVR = 1170 ± 270 dynes per s/cm 5 , and the normal SVRI = 2130 ± 450 dynes per s/cm 5 × m 2 .
Myocardial work and oxygen demand are significantly increased in the presence of shock. Numerous factors have been shown to contribute to increased myocardial oxygen consumption, including many aspects discussed above: contractility, preload, and afterload. While myocardial demand is increased during shock, supply is often reduced. In the face of elevated left ventricular diastolic pressures, coronary blood flow, particularly in the microvasculature, is compromised. Increases in the left ventricular mass from various underlying conditions can further worsen the flow in the microvasculature in the setting of shock. Additionally, in the face of hypotension, systemic diastolic pressures are lower, decreasing coronary filling. Increases in heart rate shorten diastolic time, further decreasing coronary blood flow and myocardial oxygen supply.
Recent studies have also shown that cardiac power output (CPO) can provide prognostic information in the setting of heart failure and cardiogenic shock. CPO is calculated by the following formula:
This measure takes into account not only cardiac output but also the ability of the heart to generate systemic flow and blood pressure. In other words, cardiac output alone cannot generate end organ perfusion. Maintenance of adequate arterial pressure is also necessary. For example, in end-stage heart failure, while cardiac output seems adequate to maintain perfusion, there is severe vasodilation present secondary to metabolic disarray that cannot be overcome by cardiac output alone. This measure has been shown to predict mortality in the setting of shock due to myocardial infarction, nonischemic cardiomyopathy, and acute myocarditis. Additionally, CPO is predictive of the patients who will progress to worsening heart failure before the development of shock. A CPO cutoff of less than 0.6 Watts (W) has been shown to have the best sensitivity and specificity for predicting worsening heart failure in patients admitted for heart failure, and a cutoff of less than 0.53 W predicts mortality in patients admitted with cardiogenic shock. Similarly, the pulmonary artery pulsatility index (PAPi) can be used to predict the right ventricular failure after inferior myocardial infarction or left ventricular support device implantation. PAPi is easily calculated by:
where PASP is the pulmonary artery systolic pressure, PADP is the pulmonary artery diastolic pressure, and RAP is the right atrial pressure. Data from the National Cardiogenic Shock Initiative suggest that a PAPi of <0.9 and CPO of <0.6 suggest the need for right and left ventricular support, respectively, in the setting of acute myocardial infarction.
It is important to understand the effects of various causes of shock on the pressure-volume loop to understand what hemodynamic alterations will be most helpful for the patient. In the setting of a large, acute myocardial infarction, there is an abrupt decrease in contractility, as demonstrated by a decrease in the slope of the ESPVR. This results in an acute decrease in stroke volume ( Fig. 11.14A ). If the mechanism of shock remains unchecked, the hemodynamics may further degenerate, with the eventual development of cardiogenic shock. At this point, in an attempt to maintain the stroke volume, there is a marked increase in end-diastolic volume, or preload. There is now also a marked decrease in contractility worsened by the compensatory increase in the SVR.
The effects of other shock etiologies on the pressure-volume loop may look very different from acute myocardial infarction, necessitating different therapies (see Fig. 11.14B ). In the presence of acute severe mitral regurgitation, there is a marked increase in end-diastolic volumes because of increased blood return from the left atrium. There is a simultaneous fall in forward cardiac output, even though stroke volume may remain similar. Due to reduced forward stroke volume, the mean arterial pressures fall. The abrupt increase in ventricular filling may also acutely reduce contractility, although contractility may be increased in the face of increased ventricular filling. Conversely, in cardiac tamponade, there is a marked decrease in end-diastolic volumes, resulting in a decreased stroke volume and fall in the mean arterial pressures despite the maintenance of ventricular contractility.
PATHOPHYSIOLOGY OF HEART FAILURE WITH REDUCED EJECTION FRACTION
Approximately 5.7 million Americans carry the diagnosis of heart failure, with about 550,000 new cases per year. More than 11 million physician visits per year occur for a heart failure diagnosis, and more than half of individuals with a diagnosis of heart failure will die within 5 years. The most common causes for chronic systolic heart failure are coronary artery disease and hypertension. However, there are numerous other causes of systolic heart failure. Many cases remain idiopathic with no identified etiology ( Box 11.2 ). Heart failure with reduced ejection fraction can result from a chronic progression of an underlying process such as hypertension or may result from an acute process such as following a viral infection.
Coronary Artery Disease
Hypertension
Infection
Vial, parasitic, fungal, bacterial
Infiltrative Disease
Amyloidosis, hemochromatosis
Toxins
Chemotherapeutic agents, alcohol, cocaine, amphetamines, environmental toxins
Endocrine and Metabolism Disorders
Hypothyroidism, pheochromocytoma, diabetes, nutrient deficiencies
Rheumatologic Disorders
Giant cell arteritis, systemic lupus erythematosus, scleroderma, sarcoidosis
Electrolyte abnormalities
Tachycardia induced
Peripartum
Familial, genetic
HEMODYNAMICS OF HEART FAILURE WITH REDUCED EJECTION FRACTION
The hemodynamic findings of chronic heart failure can range from almost entirely normal in compensated heart failure to significantly abnormal in the face of decompensation. As the ventricle dilates, increasing preload could generate greater myocardial stretch and thus contraction and stroke volume. However, this is at the expense of greater energy demand because of increased myocardial work. In decompensated heart failure, LVEDP elevates; it is also reflected in an elevation of the PCWP. This results in a passive elevation in the pulmonary artery (PA) and right-sided heart pressures. As pressure and volume increase and the ventricle stretches, the relatively rigid pericardium plays a greater role in determining this pressure-volume relationship. In chronic heart failure with the left ventricular enlargement, the constraining effect of the pericardium couples the ventricles via the intraventricular septum. In other words, changes in volume in one chamber influence the opposing chamber. This phenomenon is used to explain the mechanism by which diuresis improves the left ventricular stroke volume in chronic heart failure. The Frank-Starling mechanism states that a decrease in chamber volume (preload) would decrease the stroke volume; however, diuresis improves the stroke volume when there is cardiac chamber enlargement and high filling pressures because diuresis decreases the right ventricular chamber volume; this allows an increase in the left ventricular diastolic volume, thereby improving the left ventricular stroke volume. With acute heart failure, the abrupt increase in cardiac chamber volume within the confines of a relatively inelastic pericardium may cause a hemodynamic finding similar to constrictive pericarditis.
Severe left ventricular dysfunction is associated with several abnormalities on the left ventricular pressure waveform. In patients with normal systolic function, left ventricular upstroke, or the rate of left ventricular pressure rise, is brisk with a rapid decline after reaching peak systolic pressure. With the onset of diastole, the left ventricular pressure is normally very low (zero or even negative); it rises throughout diastole to reach an end-diastolic pressure of 10–12 mm Hg. Patients with severe left ventricular dysfunction may show a slow rise in the left ventricular pressure because of poor contractility that yields a triangular appearance to the left ventricular waveform ( Fig. 11.15 ). In addition, the left ventricular diastolic pressure is high early in diastole, with LVEDP reaching very high levels (40–50 mm Hg). A prominent a wave is often seen on the left ventricular tracing because of atrial contraction against an already high end-diastolic volume within a noncompliant ventricle ( Fig. 11.16 ). In patients with heart failure the LVEDP is often used as a surrogate for the mean left atrial pressure; however, a prominent a wave may interfere with the accurate estimation of the left atrial pressure. In such cases the left ventricular pre- a wave pressure, or the mean left ventricular diastolic pressure, correlates well with the mean left atrial pressure.
