Chronic aortic root pressure-loading assessment model.

PURPOSE: Percutaneous placement of transcatheter prosthetic aortic valves without cardiopulmonary bypass (CPB) continues to gain clinical acceptance. However, information on pressure-loading characteristics of the aortic root/annular areas is limited. For this reason, we designed a preclinical model, implanting an aortic root load transducer with a power source/telemetry system for chronic, conscious, loading data acquisition. This research study was conducted to determine whether an animal model could accurately measure in vivo loading. METHODS: Preoperatively, echocardiography and magnetic resonance imaging were used to determine both aortic annular and sinotubular junction dimensions, as well as ascending aortic length. Six adult sheep were placed on CPB, aortic root and ascending aorta were skeletonized and the origins of both coronary ostia were identified. Cardiac arrest with myocardial protection with cold coronary blood cardioplegia was instituted. A properly sized aortic root load-sensing device, consisting of a transcatheter aortic valve with a ring load transducer was implanted via a left apical ventriculotomy. Verification of position was determined before closure of the ventriculotomy. Each animal was weaned from CPB, and closed in routine fashion with the power source of the device placed in a subcutaneous pocket. RESULTS: There were no operative deaths or significant postoperative complications. Serial pressure-load sensing assessments in a conscious state produced reproducible proprietary data. CONCLUSIONS: This animal model allowed successful serial pressure-load sensing assessment of the aortic root/annular areas, providing a better physiological understanding of these anatomical inter-relationships. This added information could aid in future device designs with potential improved clinical outcomes.

Surgical approaches to vascular access for large-caliber devices in preclinical research models.

Percutaneous vascular access options in preclinical models are often smaller than the relevant structures in humans or undersized for early-prototype research devices. Here we describe the surgical approaches and results for surgical vascular access sites in preclinical swine and sheep models. Fourteen adult miniature swine underwent successful 18-French vascular access by means of thoracotomy to the brachiocephalic artery. In addition, 11 swine and 10 sheep underwent successful 22-French vascular access by means of retroperitoneal laparotomy to the abdominal aorta. The relevancy of approach angles and vessel tortuosity should be considered when selecting appropriate preclinical models and techniques. The techniques described are effective for delivery of large-caliber devices in preclinical testing.

Intracardiac echocardiography-guided his bundle pacing and atrioventricular nodal ablation.

BACKGROUND: His bundle pacing (HBP) results in rapid synchronous ventricular activation, but has been associated with long procedure times and compromised pacing and sensing performance. This study sought to reduce procedure time and radiation exposure, and improve electrical performance through more accurate lead placement. METHODS: Intracardiac echocardiography (ICE) was used to guide ablation and lead implantation at the His bundle, right atrial appendage (RAA), and right ventricular apex (RVA), and to assess cardiac function. Custom bipolar screw-in leads with steerable delivery sheaths and an ablation catheter were navigated using ICE (local detailed imaging) and fluoroscopy (global imaging) in anesthetized closed-chest canines (N = 6). RESULTS: HBP (N = 1) or His + ventricular septal pacing (N = 5) was achieved in all canines. The QRS width was 59.7 +/- 5.3 ms for canines in sinus rhythm (SR) and 82.8 +/- 16.6 ms for canines with HBP (P = 0.0086). The QRS width for RVA pacing was 106.3 +/- 18.4 ms (P = 0.042 vs HBP; P = 0.00013 vs SR). HBP thresholds were 3.0 +/- 1.0 volts at 0.5 ms (N = 5 due to a late exit block in one canine). The average procedure duration for His lead placement was 40 +/- 28 minutes (range of 3-81 minutes) and the total procedural X-ray exposure was 12 +/- 12 minutes (range of 2-30 minutes). Hemodynamic performance was similar for HBP and RAA pacing. CONCLUSIONS: Feasibility of ICE guidance for His pacing and precision ablation of the atrioventricular (AV) node has been shown. This anatomic approach improved accuracy, limited X-ray exposure, and might allow His pacing in patients with preexisting AV nodal block.

In-vivo motion of mitral valve annuloplasty devices.

BACKGROUND AND AIM OF THE STUDY: The long-term outcomes of mitral valve repairs are enhanced with an annuloplasty device. Although, in general, semirigid and rigid annuloplasty devices remodel the shape of the mitral valve annulus, the effect of geometric alteration on annular motion has not been fully assessed. Hence, the study aim was to investigate the influence of semi-rigid annuloplasty devices on the motion of the mitral valve annulus in adult sheep. METHODS: Sonomicrometric crystals were attached to semi-rigid annuloplasty devices (CG Future Band and CG Future COMPOSITE Ring), as well as to intra- and epicardiac sites for motion assessment in 13 sheep. Following implantation, hemodynamic and sonomicrometric measurements were collected under normal sinus rhythm and during dobutamine challenge conditions. RESULTS: Sonomicrometric measurements showed variations in the degree of device motion and timing of motion changes, depending on device size and type. Measurement of transverse device width demonstrated a pre-systolic decrease in width. For devices with the largest annular motion, the transverse device width increased during ventricular systole, with an out-of-phase increase in mitral annular septal-lateral distance during diastole. However, the geometric device septal-lateral distance showed minimal change across all devices, indicating maintenance of posterior remodeling geometry. Three-dimensional analyses revealed vertical elevation of the anterior annulus above the posterior annular plane during ventricular systole, consistent with anterior annular folding. The maximum calculated annular area occurred during early to mid-ventricular diastole, providing for maximal valve orifice area during opening of the mitral valve. The minimum annular area occurred near end-diastole to early systole, consistent with valve closing. CONCLUSION: The study results suggest that semi-rigid posterior annuloplasty devices with absent or flexible anterior mitral valve annular segments allow for a dynamic anterior annulus while maintaining aggressive posterior annular remodeling. Future studies should be undertaken to investigate the interaction between the anterior mitral valve annulus and the aortic root following annuloplasty device implantation.

Right ventricular outflow tract reconstructive model in adult sheep.

Patients born with congenital right ventricular outflow tract lesions are faced with invasive procedures to establish hemodynamic and physiological stability. Commonly, multiple subsequent surgical procedures are required due to deterioration of a previous repair. These procedures carry additive risks of mortality and morbidity. Less aggressive procedures with accompanying lower risk is ideal. Success in percutaneously placing a transcatheter valve has previously been reported; however, continued safety and efficacy of any technique needs continual assessment. We developed a model for preclinical evaluation of a percutaneous placement of a pulmonic transcatheter valve in adult sheep, including preoperative, surgical, and postoperative techniques for long-term evaluation. Adult sheep were assessed and determined to be acceptable for study enrollment. Perioperative antibiotics and analgesics were given prior to a left thoracotomy. A Medtronic, Hancock 1 valve conduit was inserted for reconstruction of the right ventricular outflow tract. The Hancock 1 valve conduit alone represented the control group and the test animals comprised the addition of a Melodytrade mark transcatheter pulmonary valve (TPV), within the Hancock 1 valve conduit. Fifteen adult sheep survived the surgical implant procedure with no perioperative mortality. There were four early postoperative deaths, three due to infection and one due to heart failure, secondary to intraoperative heart block. The remaining 11 animals remained healthy, gained weight, and survived to termination at 5 months. An initial definite-sized valve conduit was implanted, followed by inserting a single size TPV, which allowed a more accurate physiological assessment of any chosen valve. Our developed adult sheep model for percutaneous TPV implantation for right ventricular outflow tract lesions was successful for long-term assessment by utilizing our preoperative, surgical, and postoperative techniques.

Orthotopic total aortic root replacement model in adult sheep.

Prosthetic heart valves undergo mandatory preclinical animal testing prior to human clinical trials. Historically, a non-site-specific placement of a valve prosthesis has been commonly performed; however, recently site-specific placement continues to attract interest. Various animal models have been used for preclinical evaluation of both aortic and mitral valve prostheses; however, a universally accepted animal model for orthotopic total aortic root replacement with acceptable early and late mortality for long-term evaluation has been lacking. This article reports a successful orthotopic model for placement of tissue valve conduit prosthesis for total aortic root replacement in adult sheep. This model utilized preoperative echocardiographic assessment, specific intraoperative surgical techniques, and both early and late postoperative management therapies. The combination of all of these components resulted in a successful model for orthotopic placement of a tissue valve prosthesis for total aortic root replacement in adult sheep for potential long-term assessment.

Feasibility of using an implantable system to measure thoracic congestion in an ambulatory chronic heart failure canine model.

BACKGROUND: Noninvasive measures of impedance reflect alterations in thoracic fluid and pulmonary edema in acute animal and human studies. MATERIALS AND METHODS: We evaluated the feasibility of using an implantable impedance measuring device and cardiac lead system to monitor intrathoracic congestion in a pacing-induced heart failure canine model. Three devices were implanted in each of five dogs: a modified pacemaker to measure impedance from a defibrillation lead implanted in the right ventricle; an implantable hemodynamic monitoring device to measure left ventricular end diastolic pressure (LVEDP) and a second pacemaker to deliver rapid (240 pulses per minute) ventricular pacing to induce heart failure. RESULTS: All five dogs developed severe heart failure after 3-4 weeks of rapid pacing and recovered following pacing termination. The LVEDP increased and impedance decreased during pacing-induced heart failure and recovered after pacing cessation. At the end of pacing, there was a mean impedance reduction of 10.6 +/- 8.3% and a mean LVEDP increase of 18.1 +/- 4.5 mmHg compared to baseline. The impedance and LVEDP were inversely correlated (r =-0.41 to -0.85, all P < 0.05). CONCLUSIONS: In the canine model, measurement of chronic intrathoracic impedance with an implantable system effectively revealed changes in thoracic congestion due to heart failure reflected by LVEDP. These data suggest that implantable device-based impedance measurement merits further investigation as a tool to monitor the fluid status of heart failure patients.

Chronic, preclinical assessment of the Medtronic Advantage aortic valve prosthesis.

BACKGROUND AND AIMS OF THE STUDY: Medtronic, Inc. has designed and developed a new bileaflet, aortic prosthesis (Advantage) and, following an in-vitro analysis, a chronic in-vivo 20-week evaluation was performed in sheep. METHODS: Fourteen adult male and female sheep underwent implantation of either a 19 mm Advantage or St. Jude Medical (SJM) aortic prosthetic valve for chronic in-vivo evaluation, using a previously reported aortic model technique. RESULTS: There were two operative deaths, and the remaining sheep (eight with Advantage, four with SJM prostheses) underwent chronic hemodynamic and pathologic evaluations at approximately 140 days. One sheep (SJM prosthesis) died unexpectedly at 122 days; postmortem evaluation revealed valvular thrombosis, though the valve was well seated with no excessive pannus formation or paravalvular leaks. Hemodynamic and hematologic data in the remaining sheep were comparable. Pathologic examination of the remaining implanted valves revealed well-seated prostheses, with no evidence of thrombosis, no excessive pannus formation, and no evidence of paravalvular leaks. CONCLUSION: This preclinical animal study showed that the Advantage prosthesis has acceptable features, including equivalent hemodynamic and hematologic data, and a lack of pathological abnormalities when compared with a commercially available prosthetic bileaflet mechanical valve.