9 Research Techniques

Barry A. Borlaug, Paul Sorajja, Morton J. Kern

Research techniques have been and continue to be of great value in understanding common problems in cardiology. Many clinical methods that were once solely limited to the research arena now have been incorporated into routine diagnostic cardiac catheterization, such as fractional flow reserve and intravascular ultrasound (IVUS). This chapter is an overview of commonly used research procedures in the cardiac catheterization laboratory (Tables 9-1 and 9-2).

Table 9-1 Research Techniques

Objective	Method
I. Ventricular Function
1. Systolic function	Ventricular P-V relationship (simultaneous LV pressure with LV volume by echocardiogram, contrast angiogram, nuclear angiogram, or impedance catheter) Variables derived: end-systolic P-V slope, intercept; contractility (+ dP/dt)
2. Diastolic function	Ventricular P-V relationship (as above) Variables derived: end-diastolic P-V slope, intercept; relaxation (- dP/dt, τ, K)
3. Exercise studies
4. Combined hemodynamic and echocardiographic studies
II. Myocardial Blood Flow (Coronary Vasodilatory Reserve, Effects of Drugs)
	Indicator dilution; inert gas (xenon, nitrogen); thermodilution Doppler flow velocity Digital radiographic studies
III. Endothelial Function
1. QCA
2. Doppler flow
3. QCA
IV. Electrical Function (Abnormal Conduction, Excitation)
	Electrophysiologic studies His bundle Atrial and ventricular refractory periods Conduction abnormalities Inducible ventricular ectopy Bypass tracts

IVUS, Intravascular ultrasound; LV, left ventricular; P-V, pressure-volume; QCA, quantitative coronary angiography.

Table 9-2 Additional Research Techniques in the Catheterization Laboratory

LV Function	Methods
Pressure-Volume Relationships
End systole	High-fidelity pressure
End diastole	LV volume LV-gram (cineangiographic, digital) RV-gram Two-dimensional echocardiogram Impedance catheter
Wall Stress
LV mass	Quantitative ventriculography
Diastolic function	High-fidelity pressure Doppler mitral inflow
Ventricular interaction	RV/LV high-fidelity pressures
Aortic impedance	Aortic flow velocity, high-fidelity pressure
Coronary Physiology
Coronary blood flow, coronary reserve, coronary vasodilation (response to drugs)	Pharmacologic studies with papaverine and adenosine, acetylcholine Physiologic flow responses during interventional procedures such as angioplasty or hemodynamic studies
Ischemia Testing
Induced tachycardia	Electrophysiologic study
Isoproterenol, dopamine	Pharmacologic infusion
Transient coronary occlusion	Coronary angioplasty

LV, Left ventricular; RV, right ventricular.

The support staff in the cardiac catheterization laboratory may view clinical research as unnecessary, unimportant, or dangerous to the patient. These commonly held misconceptions should be dispelled by the physician, who should advocate the utility and safety of the procedure. Only skilled physicians with directed goals and institutional research board approval should apply these research techniques. The data obtained have been invaluable in identifying new therapies and advancing the frontiers of treatment for cardiac disease. It is most helpful for nurses and catheterization laboratory physicians to appreciate this problem and convey a sense of confidence and enthusiasm to the patient.

Quantitative Coronary and Left Ventricular Angiography

Although visual estimation is nearly universally used during angiography in the clinical setting, significant observer variability can occur. Quantitative coronary angiography (QCA) and ventriculography are used to help overcome these subjective limitations. Because of time constraints, these methods typically are performed off-line after data acquisition.

Quantitative Coronary Angiography

QCA can be performed using digital (or hand-held) calipers or, more commonly, computer-generated automated edge detection systems. For exact measurements, image calibration is required from an object with known dimensions, most commonly a contrast-filled coronary catheter. The catheter image is enlarged for measurement of its diameter to generate a calibration factor (mm/pixel), which is used to calculate vessel lumen size. QCA software then examines brightness values in the area of interest and uses digital algorithms to calculate vessel diameter from automatic border detection from operator selected center lines. Commonly used variables obtained from QCA are minimal lumen diameter (MLD), reference vessel diameter, acute lumen gain (final MLD – baseline MLD) after percutaneous coronary intervention (PCI), late lumen loss (follow-up MLD – final MLD) after PCI, and percent diameter stenosis (Fig. 9-1).

Figure 9-1 Frame from quantitative coronary angiographic analysis. Automatic edge and center line are performed and dimensions calibrated against object (guide catheter) of known size.

There are limitations of QCA that can lead to data variability. These include inconsistencies in image acquisition (e.g., vessel foreshortening, different imaging planes or magnification), frame selection, and differences in vessel tone between measurements. Significant discrepancy in the distances from the x-ray generator to the calibration device (i.e., catheter) and to the coronary vessel also will lead to underestimation or overestimation of the measurements. Precision can be improved by use of intracoronary vasodilators for maximal vasodilatation, complete contrast filling of the artery, and identical imaging equipment and planes between measurements.

Quantitative Ventriculography

Quantitative ventriculography is best performed with biplane imaging using a 60-degree straight left anterior oblique projection and a 30-degree right anterior oblique projection. The end-diastolic and end-systolic frames of a completely opacified ventricle during a nonectopic beat are examined using the centerline chord method. In this method, chords perpendicular to a centerline in a frame halfway between end-systolic and end-diastolic images are created, and then normalized to the end-diastolic perimeter. Regional wall motion is quantified on the basis of the degree of local chord shortening (positive values = hyperkinesis; negative values = hypokinesis) (Fig. 9-2).

Figure 9-2 Quantitative left ventriculographic wall motion analysis. Normal left ventricular (LV) wall motion shows concentric inward motion of all LV wall segments. Bottom panel shows chords and deviation from midline. The centerline method of regional wall motion analysis uses end-diastolic and end-systolic LV endocardial contours. Lower panels show how a centerline is constructed by the computer midway between the two contours. Motion is measured along 100 chords constructed perpendicular to the centerline. Motion at each chord is normalized by the end-diastolic perimeter to yield a shortening fraction. Motion along each chord is plotted for the patient (dark line). The mean motion in the normal ventriculogram group (thin line) and one standard deviation (SD) above and below the mean (dotted line) are shown for comparison. Wall motion also is plotted as the difference in units of SDs from the normal mean (right panel). The normal ventriculogram group mean is represented by the horizontal zero line.

Quantitative Coronary Flow

Doppler Coronary Flow Velocities

Coronary flow reserve (maximal coronary blood flow/resting coronary blood flow) is a global measure of vasodilation and is affected by epicardial and microvascular circulatory abnormalities (Fig. 9-3). Coronary vasodilator reserve was historically measured by coronary sinus blood flow with the use of continuous thermodilution technique. Quantitative coronary flow is determined from intracoronary arterial flow velocity using 0.014-inch Doppler-tipped sensor guidewires. In the Doppler technique, quantitative measurement of coronary flow is obtained from the use of pulsed sound waves (12 to 15 mHz) and measurement of the returning signal reflecting off moving red blood cells (Fig. 9-4). The Doppler guidewire can also be coupled with a pressure sensor (Fig. 9-5) to measure simultaneous poststenotic coronary pressure and flow. Measurement of the physiologic response of the coronary circulation to various drugs, maneuvers, and interventions, as well as assessment of the significance of coronary obstructive lesions before and after revascularization are examples of useful applications (Table 9-3). The measurement of volumetric changes in coronary blood flow can be combined with measurement of myocardial oxygen consumption (arterial and coronary sinus blood) to identify whether increases in blood flow are caused by increased myocardial oxygen demand (i.e., metabolic regulation) or by pharmacologic changes independent of myocardial demand (e.g., primary artery vasodilation or constriction).