Normalization of Pulmonary Hypertension by the Use of Left Ventricular Assist Device in Patients with End-stage Heart Failure: A Possible Contribution to Donor Pool Expansion in Lung Transplantation

SummaryHeart transplantation alone has been recognized to be contraindicated when pulmonary hypertension (PH) and elevated pulmonary vascular resistance (PVR) are irreversible, irrespective of any medical intervention by the use of inotropic agents or pulmonary vasodilators, because such patients are at an increased risk of post-transplantation right ventricular failure and mortality. Therefore, end-stage heart failure patients with concomitant fixed PH and irreversibly high PVR are considered to be heart–lung transplant candidates. Recently, left ventricular assist device (LVAD) therapy has been reported to normalize PVR through persistent unloading of the left ventricle, even in patients with medically refractory PH. Therefore, LVAD therapy could make such patients suitable for “heart-only” transplants, which contributes to appropriate donor lung allocation for lung-only candidates. We review the literature regarding LVAD use for secondary PH and present a case with end-stage heart failure that could avoid a heart–lung transplant owing to LVAD therapy

Improved long-term performance of pulsatile extracorporeal left ventricular assist device

SummaryBackground and purposeThe majority of heart transplant (HTx) candidates require left ventricular assist device (LVAD) support for more than 2 years before transplantation in Japan. However, the only currently available device is the extracorporeal pulsatile LVAD. The long-term management of extracorporeal LVAD support has improved remarkably over the years. To determine which post-operative management factors are related to the long-term survival of patients on such LVAD, we retrospectively compared the incidence of complications and their management strategies between the initial and recent eras of LVAD use, classified by the year of LVAD surgery.MethodsSixty-nine consecutive patients supported by extracorporeal pulsatile LVAD as a bridge to HTx between 1994 and 2007 were reviewed retrospectively. The patients were assigned according to the time of LVAD surgery to either group A (n=30; between 1994 and 2000) or group B (n=39; between 2001 and 2007).ResultsPatients in group B survived significantly longer on LVAD support than those in group A (674.6 vs. 369.3 days; p<0.001). The 1- and 2-year survival rates were significantly higher in group B than that in group A (82% vs. 48%, p<0.0001; 68% vs. 23%, p<0.0001, respectively). The proportion of deaths due to cerebrovascular accidents was lower (17% vs. 50%, p<0.001) in group B compared with group A. The incidences of systemic infection were similar in both groups, but the proportions of patients alive and achieving transplant surgery after systemic infection were higher in group B than those in group A (55% vs. 14%, p<0.01; 14% vs. 36%, p<0.05, respectively).ConclusionsThe long-term survival of patients even on “first-generation” extracorporeal LVAD has improved significantly in the recent era. Careful management of cerebrovascular accidents and systemic infection will play important roles in the long-term LVAD management

Androgens stimulate human vascular smooth muscle cell proteoglycan biosynthesis and increase lipoprotein binding

Vascular smooth muscle cell (VSMC) proliferation and proteoglycan biosynthesis are two critical contributors to the development of atherosclerosis. We investigated the effects of specific androgens, androstenedione, dihydrotestosterone, and testosterone, on proteoglycan biosynthesis in human VSMC derived from internal mammary arteries. Vascular SMCs were metabolically labeled with [35S]sulfate or [ 35S]methionine/cysteine to assess glyeosaminoglycans (GAGs) or proteoglycan core protein, respectively. The electroplioretic migration of radiolabeled proteoglycans was assessed by SDS-PAGE. Proteoglycan-low density lipoprotein (LDL) interactions were assessed using LDL affinity columns. Treatment of VSMCs with androstenedione (100 nM), dihydrotestosterone (10 nM), or testosterone (100 nM) increased [35S]sulfate incorporation into GAGs by 24.8% (P &lt; 0.05), 22% (P &lt; 0.05), and 32.5% (P &lt; 0.05), respectively. Treatment of VSMCs with testosterone did not alter [ 35S]methiomine/cysteine incorporation into proteoglycan core protein, suggesting that the effect of testosterone was associated with an increase in GAG length. Dihydrotestosterone (10 nM) and testosterone (100 nM) treatment of VSMCs resulted in the synthesis of biglycan and decorin that showed reduced electrophoretic mobility by SDS-PAGE, indicating an increase in GAG length