Background-We have previously shown that a specific combination of drug therapy and left ventricular assist device unloading results in significant myocardial recovery, sufficient to allow pump removal, in two thirds of patients with dilated cardiomyopathy receiving a Heartmate I pulsatile device. However, this protocol has not been used with nonpulsatile devices. Methods and Results-We report the results of a prospective study of 20 patients who received a combination of angiotensin-converting enzymes, ␤-blockers, angiotensin II inhibitors, and aldosterone antagonists followed by the ␤ 2 -agonist clenbuterol and were regularly tested (echocardiograms, exercise tests, catheterizations) with the pump at low speed. Before left ventricular assist device insertion, patient age was 35.2Ϯ12.6 years (16 male patients), patients were on 2.0Ϯ0.9 inotropes, 7 (35%) had an intra-aortic balloon pump, 2 were hemofiltered, 2 were ventilated, 3 had a prior Levitronix device, and 1 had extracorporeal membrane oxygenation. Cardiac index was 1.39Ϯ0.43 L ⅐ min Ϫ1 ⅐ m Ϫ2 , pulmonary capillary wedge pressure was 31.5Ϯ5.7 mm Hg, and heart failure history was 3.4Ϯ3.5 years. One patient was lost to follow-up and died after 240 days of support. Of the remaining 19 patients, 12 (63.2%) were explanted after 286Ϯ97 days. Eight had symptomatic heart failure for Յ6 months and 4 for Ͼ6 months (48 to 132 months). Before explantation, at low flow for 15 minutes, ejection fraction was 70Ϯ7%, left ventricular end-diastolic diameter was 48.6Ϯ5.7 mm, left ventricular end-systolic diameter was 32.3Ϯ5.7 mm, mV O 2 was 21.6Ϯ4 mL ⅐ kg Ϫ1 ⅐ min Ϫ1 , pulmonary capillary wedge pressure was 5.9Ϯ4.6 mm Hg, and cardiac index was 3.6Ϯ0.6 L ⅐ min Ϫ1 ⅐ m Ϫ2 . Estimated survival without heart failure recurrence was 83.3% at 1 and 3 years. After a 430.7Ϯ337.1-day follow-up, surviving explants had an ejection fraction of 58.1Ϯ13.8%, left ventricular end-diastolic diameter of 59.0Ϯ9.3 mm, left ventricular end-systolic diameter of 42.0Ϯ10.7 mm, and mV O 2 of 22.6Ϯ5.3 mL ⅐ kg Ϫ1 ⅐ min Ϫ1 . Conclusions-Reversal of end-stage heart failure secondary to nonischemic cardiomyopathy can be achieved in a substantial proportion of patients with nonpulsatile flow through the use of a combination of mechanical and pharmacological therapy. (Circulation. 2011;123:381-390.)

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Functional tricuspid regurgitation is a significant source of morbidity and mortality in the US. Furthermore, treatment of functional tricuspid regurgitation is suboptimal with significant recurrence rates, which may, at least in part, be due to our limited knowledge of the relationship between valvular shape and function. Here we study the dynamics of the healthy in vivo ovine tricuspid annulus to improve our understanding of normal annular deformations throughout the cardiac cycle. To this end, we determine both clinical as well as engineering metrics of in vivo annular dynamics based on sonomicrometry crystals surgically attached to the annulus. We confirm that the tricuspid annulus undergoes large dynamic changes in area, perimeter, height, and eccentricity throughout the cardiac cycle. This deformation may be described as asymmetric in-plane motion of the annulus with minor out-of-plane motion. In addition, we employ strain and curvature to provide mechanistic insight into the origin of this deformation. Specifically, we find that strain and curvature vary considerable across the annulus with highly localized minima and maxima resulting in aforementioned configurational changes throughout the cardiac cycle. It is our hope that these data provide valuable information for clinicians and engineers alike and ultimately help us improve treatment of functional tricuspid regurgitation.