Ashley M. Lewis and Michael D. Faulx
Understanding the factors that influence myocardial performance in normal and pathophysiologic states is essential for the cardiology boards. Myocardial performance is determined by the combined effects of ventricular preload, afterload, and contractility. A fourth factor, heart rate (HR), also plays a role in myocardial performance by influencing the duration of each cardiac cycle and the number of cardiac cycles per minute. Knowledge of how each of these factors responds to various disease states and therapeutic interventions provides the foundation upon which the practice of cardiovascular medicine is built.
DETERMINANTS OF MYOCARDIAL PERFORMANCE
Preload
Preload is the hemodynamic load on the myocardial wall (or the degree of stretch on the myocardial fiber) at the end of diastole, just prior to isovolumic contraction. The relationship between preload and myocardial performance was first described by physiologists Otto Frank and Ernst Starling over a century ago and is represented graphically by the Frank–Starling curve, which is discussed in greater detail in the next section. There are several experimental and clinical measures of left ventricular (LV) preload including (a) end-diastolic volume (EDV), (b) end-diastolic pressure (EDP), (c) wall stress at end diastole, and (d) end-diastolic sarcomere length. Conceptually, EDV is the most meaningful measure of ventricular preload. Clinically, EDP (by invasive measure of left ventricular end-diastolic pressure [LVEDP] or its surrogate, the pulmonary capillary wedge pressure, PCWP) is the most applicable.
Preload is predominantly determined by factors that influence venous return to the heart. Therefore, conditions that increase venous return such as volume resuscitation, supine body position, atrial contraction, skeletal muscle contraction, and decreased intrathoracic pressure (the result of deep inspiration) will increase preload, whereas conditions that decrease venous return will decrease preload. Examples of such conditions include decreased intravascular volume (severe anemia, dehydration, diuresis), venodilators (nitrates), upright posture, loss of atrial contraction (atrial fibrillation), increased intrathoracic pressure (Valsalva maneuver, positive pressure ventilation), and increased intrapericardial pressure (pericardial tamponade or constriction).
Afterload
Afterload is the resistance that the ventricle must overcome during contraction in systole. At the cellular level, it may be described as the tension in a myocardial fiber during active contraction. The relationship between afterload and myocardial performance is predicted by the force–tension relationship and is discussed in greater detail in the next section. Although there are several surrogate measures of afterload, the most commonly used are (a) central aortic pressure, (b) systemic arterial pressure, (c) systemic vascular resistance (SVR), (d) arterial impedance, (e) myocardial peak wall stress (affected by LV geometry), and (f) LV pressure. Conceptually, myocardial wall stress is the most applicable measure of afterload because it accounts for the influence of LV geometry in addition to LV pressure (see below). Clinically, measures of systemic pressure or SVR are more practical.
Myocardial peak wall stress reflects the maximum force required for the myocardium to overcome resistance and effectively expel blood during systole. This depends on the intraventricular pressure and the geometry of the left ventricle. Wall stress (σ), expressed in force per unit area of myocardium, is related to intraventricular pressure according to Laplace law:
where P is ventricular pressure, r is ventricular chamber radius, and h is ventricular wall thickness.
SVR and LV geometry are the primary determinants of afterload. However, valvular pathology such as aortic stenosis can influence afterload. Afterload is increased by increased blood pressure (hypertension, vasoconstricting drugs), increased LV radius (LV dilatation), reduced arterial elastance (atherosclerotic “stiff” arteries), and decreased wall thickness (eccentric hypertrophy, advanced cardiomyopathy). Afterload is decreased by decreased blood pressure (vasodilator therapy), increased arterial elastance, and thicker, smaller LV cavities.
Contractility
Contractility refers to the intrinsic “vigor” of the cardiac muscle. When loading conditions (preload and afterload) remain constant, increased contractility results in increased cardiac performance (stroke volume [SV]), whereas decreased contractility inhibits cardiac performance. The ejection fraction is a commonly used, though somewhat limited, surrogate for contractility. Contractility is a variable independent from loading conditions, whereas the ejection fraction can be affected by changes in preload and afterload. For this reason, the ejection fraction is really a better surrogate for SV, but since it does reflect contractility and has wide clinical availability, it remains the most popular surrogate for contractility. Contractility can be influenced by different drugs, and you are likely to encounter questions that are designed to assess your understanding of how drugs influence myocardial performance. Contractility (identified also as inotropy) is increased by drugs that alter the calcium/actin–myosin coupling mechanism. These drugs may be positive inotropes (catecholamines, phosphodiesterase inhibitors, digoxin) or negative inotropes (beta-blockers, centrally acting calcium channel blockers) (Table 4.1). The volume of myofilaments participating in the contraction process also has an effect on contractility. Contractility may increase in early aortic stenosis as the left ventricle hypertrophies, and it may decrease following the formation of scar after a myocardial infarction.
TABLE
4.1 Summary of Mechanisms of Action of Commonly Used Cardiovascular Drugs and Their Physiologic Effects
HR, heart rate; CO, cardiac output; SVR, systemic vascular resistance; MAP, mean arterial pressure.
Heart Rate
HR is a contributor to myocardial performance by virtue of its influence on cardiac cycle length and the number of cardiac cycles per minute. The principal determinants of myocardial performance are preload, afterload, and contractility, reflected clinically in the SV, the volume of blood expelled from the heart during one cardiac cycle. However, global performance of the heart is generally measured by the ability of the heart to meet the metabolic demands of the body. This is reflected in the cardiac output (CO) or cardiac index, defined by the following:
CO (L/min) = SV × HR
Cardiac index is simply the CO per unit of body surface area (BSA) (L/min/m2).
Thus, for a given SV, a faster HR results in a higher cardiac index and a slower HR results in a lower cardiac index. Under certain circumstances, HR may also influence myocardial performance during a single cardiac cycle. For example, tachycardia in a patient with severe LV hypertrophy and abnormal relaxation might shorten diastolic filling time and prevent complete isovolumic relaxation, resulting in ineffective preloading. Conversely, bradycardia in a patient with severe aortic regurgitation may overload the left ventricle by allowing a greater volume of regurgitation during diastole. Both conditions may result in reduced cardiac performance and pulmonary congestion, though for different physiologic reasons.
Myocardial Performance
Myocardial performance reflects the ability of the heart to meet the metabolic demands of the body. There are many surrogate measures of myocardial performance, but CO is arguably the most complete. CO can be assessed both invasively (thermodilution, Fick calculation) and noninvasively (echocardiography, cardiac magnetic resonance imaging [MRI]). As mentioned previously, the ejection fraction is a reasonable measure of SV. On the cardiology boards, expect to see SV or CO used in reference to myocardial performance.
GRAPHIC ILLUSTRATION OF MYOCARDIAL PERFORMANCE
The concepts of preload, afterload, and contractility can be represented graphically by the use of Frank–Starling curves, force–tension curves, and pressure–volume (PV) loops, respectively. These graphics allow the reader to visualize the interplay between the components of myocardial performance and understand how individual disease states and interventions alter myocardial performance. Expect to see these on the cardiology boards.
Starling’s Law and Frank–Starling Curves
Starling’s law dictates that cardiac performance (defined by SV) increases as preload is increased. However, there is a nonlinear relationship between EDP (a measure of preload) and SV, as shown in Figure 4.1. When afterload and contractility are held constant, reduced preload (shift along the line to the left) will reduce SV while increased preload (shift along the line to the right) will increase SV. However, if optimal preloading conditions are exceeded, the SV will no longer increase in response to higher filling pressure, which is depicted by the plateau of the curve.
FIGURE 4.1 Frank–Starling curves. As preload increases, SV increases.
In addition to preload, ventricular contractility and afterload can influence Frank–Starling curves. When contractility is increased and preload is held constant, the SV increases (entire line shifts upward and to the left). When contractility decreases, the SV decreases in response (entire line shifts downward and to the right). When afterload increases while preload and contractility are held constant, the SV decreases (entire line shifts downward and to the right), while SV increases when afterload decreases (entire line shifts upward and to the left).
Force–Tension Curves
These curves describe the relationship between CO and afterload (Fig. 4.2). When preload and contractility are held constant, any decrease in afterload will produce an increase in SV (shift along the line to the left), whereas an increase in afterload will produce a comparable decrease in SV (shift along the line to the right). As with the Frank–Starling relationship, preload and contractility also influence the force–tension relationship. As preload increases for a given afterload, SV also increases (entire line shifts upward and to the right), whereas SV decreases if preload is decreased (entire line shifts downward and to the left). When contractility increases for a given afterload, the SV increases (entire line shifts upward and to the right). When contractility decreases, SV also decreases (entire line shifts downward and to the left).
FIGURE 4.2 Force–tension curves. As afterload is reduced, SV increases.
Pressure–Volume Loops
If the ventricular volumes during one cardiac cycle are plotted against simultaneous pressures within the ventricle, a PV loop is constructed as shown in Figure 4.3. The PV loop is a rectangular illustration of the pressure and volume events that comprise a single cardiac cycle. The base of this rectangle is formed by the end-diastolic pressure–volume relationship (EDPVR), a line that describes the properties of the ventricle at the point of maximal diastolic relaxation. The EDPVR is nonlinear and analogous to the Frank–Starling curve since it illustrates the relationship between diastolic filling and myocardial performance. The end-systolic pressure–volume relationship (ESPVR) describes the systolic filling changes in the left ventricle. This curve is linear, beginning at the intersection of the pressure and volume axes, and touching the PV loop at the point of maximal end-systolic activation, when the aortic valve closes prior to isovolumic relaxation. Together these two pressure–volume relationships are the primary components of the PV loop.
FIGURE 4.3 PV loops. Time A is the onset of systole, immediately following the closure of the mitral valve. This is followed by the period of isovolumic contraction (change in pressure with no change in volume). The aortic valve opens at point B, and the point of maximal ventricular activation is reached at point C, after which the aortic valve closes. This is followed by a period of isovolumic relaxation (change in pressure with no change in volume). The mitral valve opens at point D, followed by the filling of the LV. Systole includes the time period of isovolumic contraction and ejection (point A to C). Diastole includes the period of isovolumic relaxation and filling (point C to A). The dotted lines represent the end-systolic and EDPVR, which represent the boundaries of the PV loops.
INTERPRETING THE PRESSURE–VOLUME LOOP
Ventricular Volumes
The maximum volume in the ventricle during the cardiac cycle is the EDV, the point on the x-axis where the mitral valve closes and isovolumic contraction begins. The minimum LV volume is the end-systolic volume (ESV), the point on the x-axis at the end of isovolumic relaxation prior to the opening of the mitral valve. The SV is simply the difference between the two volumes:
SV = EDV – ESV
Intracardiac Pressures
As shown in Figure 4.3, point B represents the point at which the ventricle begins to eject blood into the vasculature (opening of the aortic valve). At this time, the ventricular pressure just exceeds aortic pressure. During the ejection phase, aortic and ventricular pressures are nearly equal, so the point of greatest pressure on the loop represents the greatest pressure in the aorta and is equal to the systolic blood pressure (SBP). End-systolic pressure (Pes) is the pressure on the PV loop at the end of systole and is only slightly less than the maximal pressure (SBP). Point D, following isovolumic relaxation, represents the pressure in the left atrium (LAP) at the time the mitral valve opens. EDP is represented at the end of diastole (point A) and is influenced by the compliance of the chamber.
Compliance
Compliance is the change in volume for a given change in pressure or, in mathematical terms, the reciprocal of the derivative of EDPVR. EDPVR is nonlinear and hence compliance varies with volume. Change in volume for a given change in pressure is greater at low volumes (greater compliance) than at higher volumes (lower compliance). Changes in compliance are related to structural and pressure changes of the heart, pericardium, and thorax.
Elastance and Contractility
Defined as the linear relationship between the change in pressure for a given change in volume at end systole on the ESPVR, elastance is represented by the slope, Emax or Ees. Elastance is a surrogate for contractility because it is independent of external conditions such as preload or afterload.
Stroke Work
Stroke work represents the work of the heart during each heart beat and is represented by the area of the PV loop.
SUMMARY OF THE ACTIONS OF THE AUTONOMIC NERVOUS SYSTEM ON THE COMPONENTS OF MYOCARDIAL PERFORMANCE
α1 stimulation: 
afterload, preload
β1 stimulation: contractility, HR
β2 stimulation: 
afterload
VALVULAR HEART DISEASE AND PRESSURE–VOLUME LOOPS
The PV loops in various valvular diseases are depicted in Table 4.2 and Figure 4.4.
TABLE
4.2 Valvular Heart Disease: PV Loops
FIGURE 4.4 PV loops in various valvular disease states, with curves as depicted here for aortic and mitral regurgitation representing decompensated states.
CARDIOMYOPATHY AND PRESSURE–VOLUME LOOPS
The PV loops in various cardiomyopathies (CM) are depicted in Table 4.3 and Figure 4.5.
TABLE
4.3 Cardiomyopathy: PV Loops
ESV end-systolic volume; EDV, end-diastolic volume.
FIGURE 4.5 PV loops in various cardiomyopathies.
QUESTIONS AND ANSWERS
Questions
1. Which of the following medications will take this patient from point A to point B on the Frank–Starling and force–tension curves shown?
a. Propranolol
b. Norepinephrine
c. Hydralazine
d. Phenylephrine
e. Furosemide
2. Which of the following medications will take a patient from point A to point B on the force–tension curve shown?
a. Epinephrine
b. Phenylephrine
c. Furosemide
d. Isoproterenol
e. Digitalis
3. A patient with congestive heart failure is started on oral captopril. Which direction would this patient move on the Frank–Starling plot shown?
a.
b.
c.
d.
e.
4. Which of the following medications will take the patient from point A to point B on the curve shown?
a. Norepinephrine
b. Phenylephrine
c. Furosemide
d. Isoproterenol
e. Digitalis
5. Which of the following medications will cause the indicated change (solid loop to dotted line) on the flow–volume loop shown?
a. Norepinephrine
b. Nitroprusside
c. Milrinone
d. Hydralazine
e. Phenylephrine
6. Which of the following medications, administered acutely, will shift the pressure–volume (PV) loop as outlined below (from the solid line to the dotted line)?
a. Phenylephrine
b. Captopril
c. Hydralazine + nitrates
d. Digitalis + Intravenous fluids (IVF)
e. Epinephrine
7. Compared to the normal PV loop shown (solid lines), the PV loop to the right (dotted lines) would best reflect which of the following conditions?
a. Hypertrophic cardiomyopathy
b. Restrictive cardiomyopathy
c. Dilated cardiomyopathy
d. Pericardial constriction
e. Mitral stenosis
8. Which of the following valvular disease states would change the PV loop in the manner shown (solid lines to dotted lines)?
a. Mitral regurgitation
b. Mitral stenosis
c. Aortic regurgitation (early)
d. Aortic stenosis (early)
e. Restrictive cardiomyopathy
9. What is not a determinant of myocardial performance?
a. Compliance
b. Heart rate (HR)
c. Preload
d. Afterload
e. Contractility
10. Which parameter is used in Laplace law to calculate left ventricular (LV) wall stress?
a. Left atrial radius
b. LV wall thickness
c. Left atrial pressure
d. Right ventricular wall thickness
e. Right atrial pressure
Answers
1. Answer C: Hydralazine reduces afterload and increases stroke volume (SV) without changing preload. Propranolol acutely reduces contractility and would not be expected to improve SV. Norepinephrine and phenylephrine both increase afterload. Furosemide reduces preload.
2. Answer D: Isoproterenol reduces afterload while increasing contractility. Epinephrine and phenylephrine both increase afterload. Furosemide does not affect afterload. Digitalis increases contractility but does not influence afterload.
3. Answer D: Captopril reduces both afterload and preload. At a given contractility, it would be expected to improve SV. Preload also decreases with c but so does SV (as in diuresis, nitrates). Preload is unchanged with b and e. The decreased SV with b could be seen with an agent such as phenylephrine. The increased SV of e could be seen with a pure afterload reducer like hydralazine. Preload and SV increase with a, which might occur with IV hydration.
4. Answer A: Norepinephrine increases afterload by its effects on α1 receptors while increasing contractility by its action on β1 receptors. Phenylephrine increases afterload but should not improve SV. Furosemide does not increase afterload. Isoproterenol and digitalis can improve SV, but neither increases afterload.
5. Answer C: Milrinone increases contractility and decreases afterload, resulting in a greater SV. Norepinephrine may increase contractility but also increases afterload. Nitroprusside reduces afterload and preload but does not affect contractility. Hydralazine reduces afterload and improves SV but does not affect contractility. Phenylephrine increases afterload and does not improve SV.
6. Answer A: Phenylephrine increases afterload more than it increases preload and would be expected to reduce SV as shown. Captopril and hydralazine would reduce afterload and likely improve SV. Epinephrine would increase contractility and SV and can increase afterload at higher doses, but we would also expect to see increased contractility. Digitalis would also increase contractility, and IV fluids would increase preload as well.
7. Answer C: In dilated cardiomyopathy, the ventricle operates at higher filling pressures with greater afterload. SV and contractility are reduced, as depicted. Hypertrophic cardiomyopathy would be associated with a “spike and dome” pattern of early increased systolic pressure followed by abrupt decrease before return of systolic ejection in mid-late systole. There should be no major change in preload. Contractility is usually increased, and SV would be preserved or augmented. Restrictive cardiomyopathy and pericardial constriction can both result in lower SVs, but afterload is generally normal or reduced. There would also be early equalization of the diastolic pressure–volume curve. Mitral stenosis would be associated with reduced SV secondary to reduced preload; afterload and contractility would be unaffected.
8. Answer D: Early aortic stenosis is characterized by significantly increased afterload and increased LV systolic pressure with increased contractility and preserved SV, as shown. The increased contractility is the result of greater LV mass produced by compensatory hypertrophy. In later stages, the LV begins to dilate, increasing afterload more with a drop in contractility and SV. Preload eventually rises. Mitral regurgitation would be associated with increased diastolic filling pressure. Contractility is preserved or enhanced (at least initially) with decreasing LV systolic pressure that is proportional to the regurgitant volume. SV decreases as the regurgitant volume increases. Mitral stenosis would produce an underfilled ventricle with low SV and normal afterload. Early aortic regurgitation would greatly increase diastolic filling pressure with increased contractility and normal to increased SV. Over time, contractility would decrease and afterload would increase as the LV dilates.
9. Answer A: Myocardial performance is determined by contractility, HR, preload, and afterload. Although compliance does have an effect on preload, it is not a direct determinant of myocardial performance.
10. Answer B: LV wall thickness. The components that are used in Laplace law to calculate wall stress include LV pressure, LV radius, and LV wall thickness.