Large animal model of functional tricuspid regurgitation in pacing induced end-stage heart failure

OBJECTIVES: Functional tricuspid regurgitation (FTR) is common in patients with advanced heart failure and frequently complicates left ventricular assist device implantation yet remains poorly understood. We set out to establish large animal model of FTR that could serve as a research platform to investigate the pathogenesis of FTR associated with end-stage heart failure. METHODS: Through right thoracotomy, ten adult sheep underwent implantation of pacemaker with epicardial LV lead, five sonomicrometry crystals on the right ventricle, and left and right ventricular telemetry pressure sensors during a beating heart off-pump procedure. After 5 +/- 1 days of recovery, baseline haemodynamic, echocardiographic and sonomicrometry data were collected. Animals were paced thereafter at a rate of 220-240 beats/min until the development of heart failure and concomitant tricuspid regurgitation. RESULTS: Three animals died during early recovery period and one during the pacing phase. Six surviving animals were paced for a mean of 14 +/- 5 days. Cardiac function was significantly depressed compared to baseline, with LV ejection fraction falling from 69 +/- 2% to 22 +/- 4% (P < 0.001) and RV fractional area change from 52 +/- 11% to 25 +/- 9% (P = 0.005). All animals developed significant enlargement of tricuspid annulus (from 29.5 +/- 1.6 to 36.5 +/- 4.5 mm; P = 0.01) and right ventricle (from 21.9 +/- 0.2 to 30.3 +/- 0.6 mm; P = 0.03). Sonomicrometry derived contractility of RV free wall was depressed and at least moderate tricuspid insufficiency developed in all animals. CONCLUSIONS: Biventricular dysfunction, tricuspid annular dilatation and significant FTR were observed in our model of ovine tachycardia induced cardiomyopathy. This animal model reflects the clinical situation of end-stage heart failure patients presenting for mechanical support.