Research Techniques

9 Research Techniques

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

2. Diastolic function

3. Exercise studies  
4. Combined hemodynamic and echocardiographic studies  
II. Myocardial Blood Flow (Coronary Vasodilatory Reserve, Effects of Drugs)  

III. Endothelial Function  
1. QCA  
2. Doppler flow  
3. QCA  
IV. Electrical Function (Abnormal Conduction, Excitation)  

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

Wall Stress  
LV mass Quantitative ventriculography
Diastolic function

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)

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).

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).

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).

Table 9-3 Uses of the Doppler FloWire

Coronary vasodilatory reserve assessment

Collateral flow studies
Coronary flow research studies

Doppler Methodology and Setup

Setting up of the Doppler wire system usually takes less than 10 minutes. The timing of the reflected sound waves is used to measure blood flow velocities from moving red blood cells in a sample area that is 5 mm from the tip of the wire (and 2 mm across), far enough away so that blood velocity is not affected by the wake of the wire. The returning signal is transmitted in real time to the display console. The gray-scale spectral scrolling display shows the velocities of all the red blood cells within the sample volume. The key parameters are derived from the automatically tracked peak blood velocities, making them less sensitive to position (Fig. 9-6).

The Doppler guidewire has a forward-directed ultrasound beam that diverges in a 27-degree arc from the long axis (measured in the -6 dB roundtrip points of the ultrasound beam pattern). The pulse repetition frequency of greater than 40 Hz, pulse duration of +0.83 second, and sampling delay of 6.5 seconds are standard for clinical use. The system is coupled to a real-time spectrum analyzer, videocassette recorder, and video page printer. The spectrum analyzer uses online fast-Fourier transformation to process the Doppler audio signals. Simultaneous electrocardiographic and arterial pressure data are also displayed (Fig. 9-7). In vivo testing has demonstrated excellent correlation of the Doppler guidewire–measured velocity with electromagnetic measurements of flow velocity and volumetric flow.

Before the Doppler guidewire is placed into an artery, the patient should be given intravenous (IV) heparin (40 to 60 U/kg with target activated coagulation time >200 seconds). After diagnostic angiography or during angioplasty, the Doppler guidewire is passed through a standard angioplasty Y connector attached to a guiding catheter. The guidewire is advanced into the artery and beyond the target location (e.g., stenosis) by a distance equal or greater than 5 to 10 times the arterial diameter (approximately 2 cm). Placement in any side branches is avoided. Distal flow velocity data are obtained at rest and during hyperemia (Figs. 9-8 and 9-9).

It is important to note that Doppler coronary velocity measures only relative changes in velocity. Coronary flow is calculated as velocity (cm/s) times the vessel area (cm2). For measurement of absolute blood flow, the following assumptions must be made:

Coronary Endothelial Function Assessment

The endothelium is a monolayer of endothelial cells that line the lumen of vascular beds. Dysfunction of the endothelium is due to multiple etiologies, many of which are also implicated in the pathogenesis of atherosclerosis. The presence of endothelial dysfunction has clearly been associated with increased risk for cardiac events, even in the presence of angiographically normal–appearing coronary arteries.

In this procedure, an infusion catheter containing the Doppler wire is placed in the artery using standard techniques. Following baseline measurements of flow (i.e., velocity via the Doppler wire times area via quantitative measurement of the coronary diameter), graduated infusions of acetylcholine (10-6 M to 10-4 M) are administered directly into the coronary artery. In patients with normal endothelial function, acetylcholine infusion causes endothelial-dependent production of nitric oxide and results in vasodilatation (i.e., epicardial vasodilatation and/or increase in Doppler flow velocity; Fig. 9-11). Conversely, in patients with dysfunctional endothelium, coronary flow either fails to increase or falls because of vasoconstriction, which manifests either as blunting of the rise or an actual fall in Doppler flow velocity. Angiography is used to determine the presence of vasoconstriction, which should be treated promptly with intracoronary vasodilator therapy (e.g., calcium-channel blocker or nitrates).

Jun 5, 2016 | Posted by in CARDIAC SURGERY | Comments Off on Research Techniques

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