12 Outcomes with Use of Continuous Outpatient Milrinone Infusions in Patients with Advanced Heart Failure (AHF)

S14

The Journal of Heart and Lung Transplantation, Vol 31, No 4S, April 2012

Results: Results are summarized on table 1. Group1 : 35 pts. undergone to emergency HTx using organs retrieved from marginal donors

Variable 30 days actuarial survival rate 36 months actuarial survival rate mean in hospital stay 12 months acute rejection freedom 36 months infection freedom 36 months infection donor related freedom 36 months chronic rejection freedom 36 months cerebral haemmorage freedom hospital readmission ep./pt./year out patient clinic admission ep./ pt.year patient number undergone to HTx patient number on HTX waiting list

91% 87% 24 36% 41% 75%

⫾ ⫾ ⫾ ⫾ ⫾ ⫾

1 2 4 days 5 2 1

and had inferior 1 year survival compared with Tx/VAD.Survival on palliative milrinone is generally ⬍ 6 months and is far inferior to Tx/VAD but did have improved NYHA functional class. Group 2: 10 pts. undergone to HM II implant as bridge to decision 90% 80% 28 — 30% —

13

⫾ 1 ⫾ 1 ⫾ 1 days ⫾ 2

p.v.

WITHDRAWN

n.s. n.s. n.s. — n.s. —

14

69% ⫾ 2

—

—

100%

80% ⫾ 1

n.s.

3.1⫾ 13 ⫾ 3

n.s. n.s.

2.1 ⫾ 1 14 ⫾ 2 —

4 4

Conclusions: Results of our brief report seems to indicate that MCS used as bridge to decision in emergency conditions is yield to an excellent clinical outcome in terms of survival rate and of infection occurrence. Further experience is needed. 12 Outcomes with Use of Continuous Outpatient Milrinone Infusions in Patients with Advanced Heart Failure (AHF) P. Muthusamy,1,2 S. Madan,3 K. Mowers,3 D.E. Langholz,1 J.D. Call,1 M.B. Hanrahan,4 A.T. Davis,2,3 H. Pahwa,2 M.G. Dickinson.1 1 Cardiology, Fredrik Meijer Heart & Vascular Institute/Spectrum Health, Grand Rapids, MI; 2Grand Rapids Medical Education Partners, Grand Rapids, MI; 3Michigan State University/College of Human Medcine, Grand Rapids, MI; 4Coram Home Infusion Group, Grand Rapids, MI. Purpose: Assess outcomes on inotrope dependent (ID) AHF patients treated with continuous home infusion milrinone (HIM). Methods and Materials: Retrospective analysis of all ID patients discharged with continuous HIM support from January 2008 to October 2010.Outcomes were assessed for 3 groups:(Group 1) milrinone as a bridge to transplant or left ventricular assist device(Tx/VAD),(Group 2) milrinone weaning strategy(to improve clinical stability then empiric weaning) and (Group 3) palliative end stage strategy.ID was defined as cardiac index ⬍ 2 liters/min/m2 with signs or symptoms of end organ dysfunction despite maximal vasodilation and with improvement in hemodynamics and symptoms on milrinone infusion. Results: 49 patients (Age 61.4⫾15 years; 41 males) were treated with continuous HIM. Data is summarized. Outcome analysis for HIM

Groups

Decription, n (%)

Median HIM support (days)

One year survival

Median survival NYHA (days) (baseline)

NYHA-3 months (Of those alive)

NYHA-6 months (Of those alive)

Group 1

Bridge to Tx/VAD, 18 (36.7%)

98 (18-212)

83.3%

662 (44-1206)

3.89

2

2

Group 2

Weaned, 13 (26.5%)

109 (31-218)

73.4%

408 (242-967)

3.92

2

2

Group 3

Palliative, 18 (36.7%)

146 (4-525)

11.1%

163 (14-525)

3.76

3

3

Only 1 patient in group 1 died while on milrinone support and this was during a procedure while hospitalized prior to transplant.13 patients were able to be weaned from milrinone but had inferior survival to Tx/VAD group.Palliative HIM was associated with 5.4 months median survival.All groups had improvement in mean New York Heart Association (NYHA) functional class. Conclusions: Continuous outpatient milrinone was safely used as a temporary bridge to definitive therapy (Tx/VAD) with a 3.3 month median duration of support.Approximately one-fourth of the ID patients were successfully weaned from milrinone but these patients remained high risk

Administration of Antibodies to Self Antigens (K␣1 Tubulin and Collagen V) Results in Obliterative Bronchitis after Syngeneic Mouse Lung Transplantation V. Subramanian,1 M. Takenaka,1 V. Tiriveedhi,1 N. Benshoff,1 S. Yamamoto,1 A.E. Gelman,1 A. Patterson,1 T. Mohanakumar.1,2 1 Surgery, Washington University, St. Louis, MO; 2Pathology and Immunology, Washington University, St. Louis, MO. Purpose: Background: Immune responses against mismatched MHC and self-antigens(Ag) [K␣1tubulin (K␣1T)and Collagen V (ColV)] are postulated in immunopathogenesis of chronic rejection after human lung transplantation. The goal of this study was to determine the role of antibodies (Abs) to self-antigens in the absence of immune responses to MHC in the induction of chronic rejection [Obliterative Bronchitis (OB)] in a murine model of syngeneic left lung transplantation (LT). Methods and Materials: Syngeneic LT was performed in C57Bl/6 mice. Endotoxin free Abs to ColV and K␣1T (Group 1 n⫽5 - 200␮g/dose, intraperitoneal) or Abs to K␣1T alone (Group 2 -n⫽5) were administered on days -10, -2, 0 & weekly thereafter following LT. Graft and native lungs were analyzed by H&E and trichrome stain. Sera were tested for Abs to K␣1T and ColV by ELISA. K␣1T and Col V specific IFN-␥, IL-10 and IL-17 cells were enumerated by ELISpot. Results: Syngeneic LT had normal function with no rejection. Administration of Abs to K␣1T and ColV or K␣1T alone resulted in OB evidenced by cellular infiltration around bronchioles and vessels, epithelial metaplasia and fibrosis by day 30 both in allograft and in native lung. Control LT did not develop OB. In both groups 1 & 2 there was significant increase in cells secreting IFN␥ and IL-17 to ColV and K␣1T (spots per million cells for IFN␥ and IL-17 – ColV - 80⫾12, 15⫾4, p⬍0.05; K␣1T 79⫾15, 20⫾5, p⬍0.05, Group 2 – ColV 89⫾13, 26⫾8; K␣1T - 100⫾17, 20⫾7, p⬍0.05). Conclusions: Administration of Abs to lung specific self-antigens resulted in OB both in allograft and native lungs in a murine syngeneic LT. Abs bound to self-Ags exposed following inflammation induced by transplantation results in induction and perpetuation of autoimmunity that results in OB not only in allograft but also in native lung. 15 The Pro-Inflammatory Cytokine IL-17 Acts Directly on Bronchiolar Epithelium – Implications for Chronic Lung Allograft Dysfunction Pathogenesis S.T. Yerkovich,1,2 M.E. Tan,1 K.A. Sinclair,1 A. Fiene,1 P.M. Hopkins,1,2 D.C. Chambers.1,2 1Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Australia; 2School of Medicine, The University of Queensland, Brisbane, Australia. Purpose: Long term survival after lung transplantation is limited due to the development of chronic lung allograft dysfunction (CLAD). CLAD is associated with increased IL-17 production, which is thought to mediate neutrophil activation. We hypothesised that IL-17 may also contribute to CLAD pathogenesis by acting directly on the bronchiolar epithelium. Methods and Materials: Primary small airway epithelial cells were obtained from small airway brushings. Flow cytometry was used to quantify receptor expression (IL-17RA) directly ex vivo, and primary cell cultures were established. IL-8 was measured in bronchoalveolar lavage (BAL) by ELISA. Epithelial mesenchymal transition (EMT) was assessed following stimulation with IL-17 (1, 10, 100 ng/ml) alone or in combination with TGF␤ (10ng/ml). Results: Bronchiolar epithelial cells were found to express the receptor for IL-17 and expression was higher in patients with CLAD (15.6% (15.332.3; n⫽5) vs 7.3% (6.5-10.1; n⫽11); p⫽0.020). Increased IL-17 receptor expression was associated with increased BAL IL-8 (r⫽0.649, p⫽0.006), suggesting cross-regulation between IL-8, IL-17 and its receptor. In vitro,