Cardiac catheterization and angiocardiography continue to play an important role in the management of patients with valvular heart disease. ¹ Although in the majority of patients, information obtained from the history, physical examination, and noninvasive imaging studies (electrocardiogram, chest radiograph, and echocardiogram) is sufficient to establish the correct diagnosis and allow appropriate clinical decision making, including referral for percutaneous or surgical intervention, cardiac catheterization and angiocardiography are often required in select patients with valvular heart disease. They include patients (1) who require coronary angiography prior to surgical intervention, (2) who have complex multivalve disease for which data from echocardiography and cardiac catheterization must be integrated, (3) who have suboptimal echocardiographic imaging results (large body habitus, obesity, chronic lung disease), (4) in whom discrepancies exist between the clinical information and findings from echocardiography, (5) in whom the diagnosis remains uncertain despite echocardiography and additional no-invasive imaging studies, (6) with low-gradient aortic stenosis (AS) when the administration of dobutamine can differentiate between true and “pseudo”–aortic stenosis, and (7) being evaluated for transcutaneous aortic valve implantation.

Various protocols can be used in the cardiac catheterization laboratory to evaluate patients with valvular heart disease ( Table 7-1). The fundamental basis of each approach relies on the premise that obtaining accurate and detailed measurements during the procedure is essential so that the subsequently derived data remain accurate. Pressure and cardiac output measurements should be performed prior to angiocardiography. A number of potential sources of error can be present during the cardiac catheterization laboratory procedure ( Table 7-2). The specific methods and techniques used during a cardiac catheterization procedure are selected to provide answers to specific clinical questions. The significance of the hemodynamic findings must be integrated with the complete set of clinical data, including information from the history, physical examination, electrocardiogram, chest radiograph, and echocardiogram.

TABLE 7-1

Protocol for Evaluation of Valvular Heart Disease at Cardiac Catheterization

TABLE 7-2

Potential Sources of Error in Evaluation of Valvular Heart Disease at Catheterization

Pressures

Direct measurement of left ventricular (LV) pressures throughout the entire cardiac cycle provide valuable data on LV systolic function, although the effect of concurrent valvular disease must also be taken into account. The rate of rise of LV pressure (dP/dt) during isovolumic contraction provides a relatively load-independent measure of LV systolic function, which is particularly useful in patients with altered loading conditions due to valvular disease.

Pressure-Volume Loops

The relationship between LV pressure and volume throughout the cardiac cycle can be examined in detail by graphing instantaneous pressure (on the vertical axis) against volume (on the horizontal axis). LV stroke volume is the distance on the horizontal axis between end-diastole and end-systole, whereas LV stroke work (the integral of pressure times volume over the cardiac cycle) is the area enclosed by the pressure-volume loop. When pressure-volume loops are recorded under different loading conditions, the slope of the end-systolic pressure-volume relationship, termed elastance or E_max, provides a load-independent measure of LV systolic function.2,3

Valvular heart disease characterized by pressure overload of the left ventricle results in a taller pressure-volume loop that is shifted upwards, reflecting the higher ventricular systolic pressures and greater LV stroke work. Volume overload of the left ventricle also increases stroke work, resulting in a larger loop that is shifted upwards and to the right. However, despite these shifts in the pressure-volume loop, the slope of the end-systolic pressure-volume relationship remains normal in patients with valvular disease and compensated ventricular systolic function. A reduced slope indicates impaired contractility superimposed on the pressure and/or volume overload state.

In practice, measurement of pressure-volume loops is technically demanding and often not required for clinical decision making. Ventricular pressures must be recorded with high-fidelity catheters, and volumes must be determined at multiple points in the cardiac cycle using either contrast or radionuclide angiography or experimental approaches such as a conductance catheter. ⁴ Thus, although this approach provides insight into the pathophysiology of disease and provides essential information in research studies, it is rarely used in the routine clinical management of patients with valvular heart disease. ⁵

Evaluation of Left Ventricular Systolic Function

Evaluation of LV systolic function includes ventriculography, measurement of cardiac output, and measurement of LV pressures throughout the cardiac cycle. Contractility is defined as the intrinsic ability of the myocardium to shorten, independent of loading conditions. However, measurement of LV contractility in the clinical setting is problematic. The reason is that most conventional measures of LV systolic function depend on both ventricular preload and afterload, as well as myocardial contractility. Increased preload, defined as LV end-diastolic volume or pressure, increases myocardial shortening as described by the Frank-Starling relationship. In contrast, afterload, defined as the resistance or impedance to LV ejection, is inversely related to myocardial shortening. Loading conditions are frequently altered in patients with valvular heart disease. For example, with AS, afterload is increased and with aortic regurgitation, both afterload and preload are increased. These alterations complicate the assessment of LV systolic function.

Angiocardiography

LV end-diastolic volume (EDV) and end-systolic volume (ESV) can be calculated by tracing the respective endocardial boundaries on angiographic images and applying a validated geometric formula for volume calculation. Stroke volume (SV) is calculated as follows:

and ejection fraction (EF) as:

The stroke volume (cardiac output divided by heart rate) calculated by angiocardiography represents the total amount of blood ejected by the ventricle, whether that blood is ejected forward into the aorta or backward into the left atrium across an incompetent mitral valve. Thus, angiographic stroke volume is termed “total” stroke volume.

The geometric formulas for angiographic calculation of volume (V) typically assume a prolate ellipsoid shape of the left ventricle. Endocardial border tracings from two orthogonal views of the ventricle (right and left anterior oblique projections) are used to measure the area (A) and length (L) of the ventricle with the minor axis diameter (D) calculated for each view as:

where D_a and D_b are the minor axis dimensions in the two orthogonal views.

In the clinical setting, a single-plane right anterior oblique angiogram using the modified for mula of Dodge and Sandler ⁶ also provides acceptable results:

Although both angiography and echocardiography depend on manual border tracing, a slight, but consistent, overestimation of LV volumes by angiography is due to filling of the ventricular trabeculations by contrast agent so that the traced endocardial border represents the outer edge of the myocardial trabeculations, in contrast to echocardiography, in which ultrasound is reflected from the inner edge of the myocardial trabeculations so that the volume tends to be underestimated slightly.7–9 In addition, the volume occupied by the papillary muscles (which are excluded from the endocardial border tracing) needs to be taken into account. Regression equations have been derived in an attempt to correct for the overestimation of volume on angiography resulting from these two factors, such as the following:^10–12

where V_c is the calculated volume and V is the corrected volume.

With careful angiographic technique, tracing of endocardial borders by an experienced observer, and use of appropriate correction factors, ventricular volumes derived from angiography correlate well with directly measured volumes and with echocardiographic volumes.13–16 A biplane imaging approach, using borders traced from both the right and left anterior oblique radiographic projections,^17,18 provides accurate results with a mean difference for measurement variability of 6 to 10 mL for end-systolic and 7 to 20 mL for end-diastolic volumes. ¹⁹

Technical factors important in the performance of ventricular angiography include the need for complete opacification of the ventricle with clear definition of the endocardial borders at both end-diastole and end-systole. This goal can be achieved with a 6 French side-hole pigtail catheter, a power contrast injector, and use of an injection rate and volume appropriate to the type of catheter, ventricular chamber size, and hemodynamics. A nonionic contrast agent is optimal in patients with valvular disease to avoid myocardial depression and/or hemodynamic changes. Correct positioning of the catheter in the midventricle is needed to completely opacify the chamber, to prevent movement of the catheter during the contract injection, and to minimize the risk of arrhythmias. Optimal catheter positioning also avoids artifactual mitral regurgitation due to entrapment of the catheter in the mitral valve apparatus. In addition, a correction factor for the effect of magnification must be determined by filming a calibrated grid at the estimated level of the ventricle. Other factors that affect the accuracy and reproducibility of angiographic volumes are image quality, the experience of the individual tracing the endocardial borders, heart rate and rhythm, and the potential cardiodepressant effect of the contrast agent.

Methods for determining LV mass by angiographic techniques have been described, with LV mass calculated on the basis of the thickness (h) of the anterior wall (assuming a symmetric thickness around the ventricle), ventricular diameter in anterior-posterior (D_AP) and lateral (D_lat) views, long-axis length (L), and ventricular volume (V), as follows:

However, ventricular mass calculations are limited by the inaccuracy in measuring LV wall thickness from the angiographic image and thus are not widely used clinically.20,21

LV angiography also allows qualitative and quantitative assessment of wall motion in patients with valvular heart disease and concurrent coronary artery disease.22,23

Cardiac Output

Cardiac output can be calculated during cardiac catheterization by the dilution of a known concentration of an indicator (e.g., dye, oxygen, or cold saline) as it passes through the vascular bed. This concept is illustrated by the injection of a known volume and concentration of dye (typically indocyanine green) into the venous circulation. From the rate at which this dye appears in the arterial circulation, the volume of blood the dye was diluted in (i.e., the cardiac output) can be calculated. Although indicator dilution dye curves provide accurate measurement of cardiac output, the procedure is time consuming and depends on meticulous technique, and other methods are now more commonly used.

Fick Technique

Oxygen serves as the “indicator” for cardiac output calculations in the Fick method. The Fick principle states that the uptake or release of oxygen by a tissue is the product of the amount of oxygen delivered to the tissue times the difference in oxygen content between the blood entering and the blood leaving the tissue. ²⁴ Thus, for the uptake of oxygen by the lungs:

If the amount of oxygen consumed by the patient (oxygen uptake), and the oxygen content of pulmonary arterial (PA) and pulmonary venous (PV) blood are measured, this equation can be solved for pulmonary blood flow, as follows:

In the absence of an intracardiac shunt, pulmonary and systemic blood flows are equal, so this method provides a measure of systemic (or forward) cardiac output, which can be calculated as follows:

where O₂ consumption is measured in mL O₂/min and O₂ content as mL O₂/100 mL blood (often referred to as “volume percent”).

To ensure that the sample of venous blood represents total venous return with adequate mixing of the sample, a pulmonary artery blood sample is used for mixed systemic venous oxygen content in this equation (in the absence of an intracardiac shunt). Although pulmonary venous blood provides the most accurate sample of oxygenated blood, the arterial sample is obtained from a systemic artery or the left ventricle. When an intracardiac shunt is present, separate calculations for systemic and pulmonary blood flows (using the appropriate arterial and venous oxygen contents) allow determination of the shunt ratio.

In clinical practice, oxygen consumption is usually measured by the polarographic O₂ method or by the paramagnetic method. Collection of expired air using the Douglas bag method is rarely used. The polarographic method uses a hood or face mask with the rate of air flow through the servo unit controlled by an oxygen sensor cell to maintain a constant fractional content of oxygen. Oxygen consumption () then is calculated from the fractional content of oxygen and flow rates of air entering and exiting the patient mask, assuming a respiratory quotient of 1.0. The paramagnetic method measures both oxygen and carbon dioxide in expired air, allowing calculation of the respiratory quotient for each patient. In recent years, there has been a trend to estimate oxygen consumption with the use of derived equations. ²⁵ However, use of these derived equations is inaccurate, especially in patients with increased body mass index. ²⁶

The arteriovenous oxygen difference is calculated from measurement of oxygen content in simultaneously drawn samples of arterial and mixed venous blood collected midway during the oxygen consumption measurement. Oxygen content is typically calculated as oxygen saturation multiplied by the theoretic oxygen capacity, which is estimated from the patient’s hemoglobin (Hgb) level as follows:

For accurate cardiac output calculations, it is important that the arterial and venous oxygen samples are collected from the correct sites with prompt processing of the samples and that oxygen consumption and content measurements are simultaneous. Even with careful technique, the average error in measuring oxygen consumption is approximately 6% ²⁷ and the error in measurement of the arteriovenous oxygen difference is approximately 5%, ²⁸ resulting in an error in cardiac output measurement of about 10% by the Fick method. ²⁹ Measurements are more inaccurate if physiologic changes that affect cardiac output, such as heart rate and loading conditions, occur during the analysis period. Use of an assumed, rather than measured, oxygen consumption also leads to significant error because there is wide variation in the normal rate of oxygen consumption in adults.^30,31 Fick cardiac outputs tend to be more accurate for low outputs, and thermodilution outputs are more accurate at high flow rates.

Thermodilution Method

Measurement of cardiac output by the thermodilution method is widely used in the evaluation of patients with valvular heart disease. With the thermodilution method, a known volume of cold saline is injected into the right atrium while a thermistor in the pulmonary artery continuously records temperature ( Figure 7-4). Cardiac output is then calculated from the known temperature (T) and volume (V) of the injectate, and the integral of temperature over time (ΔT/dt) in the pulmonary artery.^32,33

where the constant incorporates factors for the specific gravity and specific heat of blood and the injectate (1.08 if the injectate is 5% dextrose). In addition, an empirical correction factor (multiplication by 0.825) is needed for the effect of warming of the injectate as it passes through the catheter.34,35

As with the Fick method, the thermodilution method measures the “forward” cardiac output, specifically the output of the right heart. Advantages of the thermodilution method include ease and repeatability of use, thus allowing multiple measurements over short time intervals with a reasonable accuracy (a reproducibility of about 5%-10% with proper technique). ³⁶ Disadvantages include relatively poor accuracy at low cardiac outputs ³⁷ and dependence on careful attention to technique, in particular the avoidance of warming of the injectate. Because this method depends on even mixing of the injectate with the right atrial (RA) blood, thermodilution output measurements are inaccurate when significant tricuspid regurgitation is present. Significant tricuspid regurgitation results in a prolonged decay in the temperature-over-time curve.

Evaluation of Stenosis Severity

Measurement of Pressure Gradients

Normal cardiac valves offer little to no resistance to blood flow when the valve is open in either systole (semilunar valves—aortic and pulmonic) or diastole (atrioventricular valves—tricuspid and mitral). In the setting of disease, restriction to leaflet opening (stenosis) occurs and blood flow across the valve is hindered. Resistance to blood flow results in a pressure drop or gradient across the valve. The principles of evaluating the severity of stenosis of each of the cardiac valves are similar and involve: (1) measurement of the pressure gradient, (2) analysis of the pressure waveforms, (3) measurement of cardiac output, (4) calculation of the valve area and, occasionally, (5) angiocardiography of the chamber upstream of the site of stenosis.

Basic Principles

Pressure gradients are most accurately measured with use of two transducers that allow for simultaneous measurement of the upstream and downstream pressures. A systematic approach to the review of pressure waveforms includes assessment of: (1) cardiac rhythm, (2) pressure scale and pressure per division, (3) recording speed (i.e., paper speed), (4) pressure values across the valve, (5) pressures in all adjacent cardiac chambers ( Table 7-3), (6) the rate and shape of the upslope and downslope of pressure waveforms, and (6) recording artifacts. Both technical and physiologic factors can affect the measured pressure gradients (see Table 7-2).

TABLE 7-3

Normal Values at Cardiac Catheterization (Supine, Resting Adults)

Technical Factors

Technical factors can significantly affect the accuracy of the reported transvalvular gradients. The frequency response of the pressure measurement system significantly affects the recorded pressure waveform. Although micromanometer-tipped catheters have an optimal frequency response (at least 20 cycles/second) for intracardiac pressure recording, these catheters are expensive and require meticulous technique. In the clinical setting, the fluid-filled catheters and strain-gauge external transducers that are commonly used have a frequency response of only 10 to 20 cycles/second. The frequency response can be optimized by use of stiff wide-bore catheters, a short length of connecting tubing, and a low-density liquid.

External pressure transducers are subject to a phenomenon called “ring-down,” which results from the conversion of pressure energy to an electrical signal, similar to the sound resulting from striking a bell. The use of a fluid-filled catheter between the chamber of interest and the transducer amplifies this phenomenon, leading to apparent fluctuations in the recorded pressure signal. This phenomenon, called “underdamping,” is characterized by a waveform consisting of diminishing harmonic oscillations of the underlying pressure signal. To counter this effect, the recording system is damped just enough to avoid excessive oscillations while maintaining the frequency response of the system. “Overdamping” must also be avoided as it can lead to underestimation of pressure gradients. Damping can typically be optimized by using short, stiff tubing to connect the catheter to the pressure transducer, minimizing the number of connections in the system, and using a contrast agent (instead of saline) to fill the catheter.

Pressure recording systems must be zeroed and calibrated both before and after data collection. Calibration is optimally performed with the use of a known input pressure, such as with a mercury manometer, but many systems now include an electronic calibration that is usually adequate. The zero and the reference standard need to be rechecked periodically during and at completion of the study to avoid erroneous data interpretations. When two catheters are used to measure pressures simultaneously on both sides of a stenotic valve, the calibrations are checked together, and if possible, data are re-recorded after the transducers are switched to the other catheters to avoid any systematic bias.

Pressures are recorded at a fast sweep speed to allow accurate time measurements and to display the waveform in enough detail to allow analysis of the degree of damping and the subtleties of the pressure waveform. The vertical axis is adjusted, depending on the pressures being recorded, to utilize the full height of the recording while including the pressure waveforms of interest on the scale. For example, left atrial (LA) and LV pressures across a stenotic mitral valve might be recorded on a 0 to 25 mm Hg scale, whereas severe AS might require a 0 to 200 mm Hg scale.

Physiologic Factors

The exact locations of the pressures recorded upstream and downstream of a stenotic valve can significantly affect the measured transvalvular gradient, and occurs for several reasons. First, the timing of the pressure waveform is different closer to the valve from that at a greater distance from the valve, so that realignment of the waveforms may be needed for accurate gradient calculations. For example, the femoral artery pressure upstroke is delayed in comparison with the central aortic pressure as predicted by the velocity of pressure propagation between these two sites. If a femoral artery waveform is used in place of central aortic pressure to calculate the aortic transvalvular gradient, this timing difference needs to be taken into account. Similarly, if the diastolic pressure curve uses the the pulmonary capillary wedge pressure in place of directly measured LA pressure in a patient with mitral stenosis, failure to consider timing differences may lead to erroneous mitral gradient calculations.

Second, the shape of the waveform adjacent to the valve and that of a more distal waveform may affect the apparent transvalvular gradient. This is most evident in comparison of central aortic and peripheral arterial (e.g., femoral artery) pressures. Because of summation of the transmitted and reflected pressure waveforms, the femoral artery pressure curve is narrower with a higher peak than the central aortic pressure curve, a phenomenon known as “peripheral amplification.” Simultaneously measured central aortic and LV pressures are used whenever possible for calculation of transaortic pressure gradients, but if only a femoral pressure is available, realignment of timing and correction of the peripheral amplification are needed.

The third physiologic issue that may affect the measured transvalvular gradient is the phenomenon of pressure recovery that occurs distal to a site of stenosis. Pressure recovery is especially important with AS.38–40 As the high-velocity jet flows through the stenotic orifice, it decelerates and expands distal to the valve. The associated turbulence results in an increase in aortic pressure (“pressure recovery”) such that the pressure difference between the left ventricle and the distal ascending aorta is less than the pressure difference between the left ventricle and the stenotic orifice itself. Although pressure recovery may account for some of the observed discrepancies between Doppler and catheter-based data and conceivably could lead to underestimation of stenosis severity, the magnitude of this effect in the clinical setting appears to be small (approximately 5-10 mm Hg) and is unlikely to affect clinical decision making. Pressure recovery is greatest when stenosis severity is mild and aortic root dimension is small, and is least with severe stenosis and poststenotic dilation. Potential underestimation of stenosis severity due to pressure recovery can be avoided by recording pressures immediately adjacent to the valve on the downstream side of the stenosis.

Several other factors may also affect recorded pressure gradients. Transaortic pressure gradient may be affected by the presence of the catheter itself in the stenotic orifice. The catheter may increase the transvalvular pressure gradient either by further decreasing the cross-sectional flow area or by inducing aortic regurgitation. ⁴¹ Other physiologic variables that may affect the pressure gradient are the effect of atrial contraction, cardiac arrhythmias, and the compliance of the receiving chamber when regurgitation is present. Irregular heart rhythms affect measured pressure gradients in valvular stenosis because of the varying volume flow rates across the valve, necessitating averaging of several beats for clinical interpretation.

Aortic Valve

The most commonly encountered valvular heart disease condition in the cardiac catheterization laboratory in recent years is AS. With the widespread use of echocardiography, the diagnosis and severity of AS are frequently known prior to referral of the patient to the cardiac catheterization laboratory. With more elderly patients being offered treatment for AS with minimally invasive options (e.g., transcatheter aortic valve implantation), the number of patients with AS referred for invasive hemodynamics will continue to rise. The cardiac catheterization procedure therefore usually involves confirming the findings of echocardiography. Occasionally, however, the diagnosis and/or severity of stenosis remains in question, and cardiac catheterization is requested to further clarify the situation. In this setting, it is essential to obtain complete, accurate, and reliable data during the procedure. Patients with low-output and/or low-gradient AS represent a unique and challenging subset and are discussed separately.

Pressure Gradients

All pressures should be measured prior to contrast ventriculography and angiography. A variety of catheters and techniques can be used to the cross the aortic valve in a retrograde manner to measure the pressure gradient. A 0.038-inch standard straight wire in combination with a pigtail catheter, Judkins right, or Amplatz left coronary catheter is commonly used. ⁴² Occasionally, a catheter specifically designed to cross the aortic valve, called a Feldman catheter, may be required. ⁴³ When the straight wire cannot be passed across the valve, supravalvular angiography may be useful to localize the position and orientation of the valve orifice. The position and movement of calcium within the valve leaflets may also suggest the location of the valve orifice. Although hydrophilic straight wires can also be used to cross the aortic valve, the hydrophilic wire coating may increase the risk for valve leaflet perforation. Probing the aortic valve orifice with the wire should be done in less than 2-minute increments, with the wire removed and the catheter carefully flushed prior to reinsertion and another attempt to cross the valve. Although the risk of retrograde passage of a catheter across a narrowed and diseased aortic valve is small, one study has found that 3% of patients undergoing cardiac catheterization experienced a clinically significant neurologic event and 22% had magnetic resonance imaging evidence of an acute cerebral embolic event. ⁴⁴ In the setting of severe aortic valve calcification or critical AS, or when coexisting mitral stenosis is present, transseptal puncture should be considered.

The pressure gradient between the left ventricle and the aorta can be described by three invasive measurements: (1) the mean gradient, (2) the peak-to-peak gradient, and (3) the maximum gradient ( Figure 7-1). The mean gradient represents the area under the LV-aortic pressure curve and corresponds to the mean gradient measured by echocardiography. The peak-to-peak gradient has no true physiologic meaning and represents the difference between maximum aortic and the maximum LV pressures. Note that these maximum pressures do not occur at the same time and that the peak-to-peak gradient is not the same as the maximum gradient. Although the peak-to-peak gradient is easily measured with computer-assisted software, it is not useful in classifying the severity of AS. The maximum gradient represents the maximum difference that can be measured between the left ventricle and aorta during systole and corresponds to the maximum instantaneous gradient measured by echocardiography. The maximum gradient occurs early during ventricular ejection, before the peak LV pressure.