Dos and don'ts in large animal models of aortic insufficiency

Figure 1. (A) Fluoroscopic image of a PigTail catheter which is positioned in the aortic valve cusp, hence enabling the assessment of PV loop catheter segments that are reliably positioned within the left ventricle; (B) If uncertainty regarding the PV loop segments within the left ventricle persists, contrast agent can be delivered through the PigTail catheter, hence providing an aortographic image clearly demonstrating the separation between the aorta and the left ventricle; (C) Typical “figure of 8” PV signal originating from the segment placed at the level of the aortic valve or above. Such segments should not be taken into further analysis; (D) Paradox composite PV loop curves demonstrating volume increase during systole and volume decrease during diastole. If such curves occur, re-positioning of the PV loop catheter needs to be considered.

Figure 2. Due to the 2D character of echocardiographic imaging, two distinct perpendicular projections (long and short axis) are necessary for precise procedural navigation; (A) Transesophageal (TEE) long axis echo image demonstrating the final position of the steerable sheath on target for creation of the defect at the leaflet hinge point in the right coronary cusp (RCC) of the aortic valve; (B) Once such position is reached, intra-cardiac echo should be used to confirm the position in the short axis image; (C) Fluoroscopy is used to visualize the piercing guide wire during its positioning, and for control of the PTCA balloon inflation; (D) Inflated PTCA balloon used for defect dilation can be also visualized in TEE long axis view.

Figure 3. (A) In TEE, pigs display a unique feature of thickened septal wall. Especially the portion directly beneath the aortic valve, corresponding to the location of the RCC. Thickening of this region becomes prominent, especially during end-systole and early diastole; (B) In CT however, usually only general thickening of the septal wall can be observed, and often no prominent “bulge” is detectable; (C) An aortogram is performed following an erroneous piercing in the RCC region. A direct flow of contrast to the right ventricle could be observed demonstrating an aorto-right ventricular communication; (D) Upon pathological examination a fistula connecting the aortic root and the right ventricle was found.

Figure 4. Echocardiography and aortography can be used for verification of the aortic valve defect; (A) Color Doppler image of the aortic insufficiency jet created in the NCC region of the aortic valve; (B) Aortographic image of the same animal in latero-lateral position also demonstrating the existence of the regurgitant jet. Such images can later be used for densitometric quantification of the regurgitant volume.

Figure 5. Postmortem examination of defect size, location, and potential extra-valvular injuries created during the procedure. (A) Demonstrates the defect precisely placed at the hinge point of the aortic leaflet in the RCC region; (B) Slight injury on the endocardial surface of the left ventricle, most likely caused during the insertion of the piercing guide wire.

Figure 6. Echocardiography immediately after the creation of the PVL defect in sx consecutive animals. (A–C) Defects created in the RCC annular region; (D–F) Defects created in NCC annular region; PVL jet originating from the NCC region have a trajectory along the anterior leaflet of the mitral valve and can be fully visualized along their path in the LV. RCC jets on the other hand either flow along the septum or at a steep angle across the LV.

Figure 7. Stable position of the PV loop catheter during the entire procedure is fundamental for the evaluation of the effects of aortic regurgitant jets on left ventricular performance. (A) Marked change in PV loop curves following the removal and reinsertion of the catheter after the defect creation. Such changes render the comparison of the LV performance between the healthy state (light and dark blue loops) and aortic insufficiency state (red and yellow loops) particularly challenging and potentially misleading; (B) By keeping the catheter in a stable position during the entire procedure reliable measurements could be performed, delineating effects that aortic regurgitation causes to LV performance (light blue vs. yellow loops). Furthermore, investigations under pharmacologically changed hemodynamic conditions are possible (dark blue vs. red loops).