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Nitric oxide inhalation modulates endothelin-1 and big endothelin-1 after left ventricular assist device implantation
The Journal of Heart and Lung Transplantation Volume 20, Number 2
Abstracts
268 NITRIC OXIDE INHALATION MODULATES ENDOTHELIN-1 AND BIG ENDOTHELIN-1 AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION F.D. Wagner1, S. Buz1, C. Knosalla1, M. Loebe1, R. Hetzer1, B. Hocher2; 1Deutsches Herzzentrum Berlin, Berlin, Germany; 2 Charite, Berlin, Germany Purpose: Nitric oxide inhalation therapy is now an established therapy in the treatment of right ventricular dysfunction due to pulmonary hypertension after left ventricular assist device (LVAD) implantation. Inhaled nitric oxide (iNO) decreases right ventricular afterload by its selective vasodilating effect on the pulmonary circulation. It is known that endothelin-1 (ET-1) contributes to pulmonary hypertension. The effects of iNO on circulating ET-1 and big endothelin (big ET-1) in LVAD-patients were investigated in this study. Methods: On weaning from cardiopulmonary bypass (CPB) 15 consecutive patients were treated with iNO because of right ventricular compromise secondary to pulmonary hypertension. Plasma ET-1 and big ET-1 concentrations were measured preoperatively, on CPB prior to iNO, 12, 24, and 48 hrs. postoperatively, as well as 72 hrs after cessation of iNO. Results: Mean initial iNO dose was 33 ppm (20-40 ppm). NO therapy was successfully weaned in all patients without a rebound phenomenon. ET-1 and big ET-1 were increased preoperatively (1.50 ⫹/- 1.9 and 3.87 ⫹/- 3.0 fmol/ml, respectively). ET-1 concentrations were highest on cardiopulmonary bypass (2.00⫹/1.56 fmol/ml). ET-1 and big ET-1 decreased significantly during iNO therapy and were lowest 72 hrs after cessation of iNO (Table 1). The iNO dose and plasma ET-1 levels correlated significantly (p⬍0.001). A significant correlation was also found between ET-1 and PA-pressures, PVR and PVR/SVR ratio, but not with CI and SVR. Conclusion: Since it is known, that ET-1 mediates pulmonary hypertension, we suggest a two-fold effect of iNO therapy: first a selective vasodilation of the pulmonary vasculature and second NO-mediated inhibition of one of the most potent vasoconstrictors of pulmonary vessels: ET-1. Table 1
ET-1 fmol/mL Big ET-1 fmol/mL
12h
24h
48h
72h post iNO
1.5⫹/-1.4 5.3⫹/-5.5
1.3⫹/-1.6 3.7⫹/-2.0
1.1⫹/-1.2 3.6⫹/-2.9
0.7⫹/-0.4 2.2⫹/-0.8
269 LVAD THERAPY IMPROVES UTILIZATION OF DONOR HEARTS: IMPLICATIONS FOR PROLONGED INOTROPIC THERAPY K. Aaronson, M. Eppinger, S. Wright, F.D. Pagani; University of Michigan, Ann Arbor, MI, USA Background: It is generally accepted that LVAD therapy improves post-transplant survival. However, the risk of LVAD implant generally discourages its use in favor of prolonged inotropic therapy. Methods: We investigated the impact of LVAD therapy on heart transplant outcomes in adult patients (age ⱖ 17 years) from January 1, 1995 to October 1, 2000. Sixty-two patients underwent LVAD implant as a bridge to transplant (TX). Survival (KM) for 50 patients with outcomes (death or TX) was calculated from the
241
time of LVAD implant or time of TX and compared to survival for 29 patients who underwent TX with inotropic therapy (UNOS status 1,1A,1B), and 82 who underwent TX as UNOS status 2. Results: TX survival in patients with prior LVAD support was superior compared to survival in patients undergoing TX as UNOS status 1 with inotropic therapy or as UNOS status 2 (see Table; ( ) - no. at risk). Survival from the time of LVAD implant (includes TX operation) was equivalent to survival for patients undergoing TX as UNOS status I with inotropic therapy. Conclusions: Long-term survival in patients undergoing LVAD therapy from the time of LVAD implant was equivalent to survival of patients undergoing TX as UNOS status 1 with inotropic therapy from the time of transplant. However, there were fewer transplant deaths in patients receiving LVAD therapy. LVAD therapy yields similar long-term survival with conservation of donor hearts. Given the critical shortage of donor organs, LVAD therapy as opposed to prolonged inotropic therapy may be preferential. Group
1 Year
3 Year
5 Year
Survival for Status 1 with LVAD from TX Survival for Status 1 with LVAD from LVAD Implant Survival for Status 1 with Inotropic therapy from TX Survival for Status 2 from TX
95%(31)
92% (6)
92%(1)
80%(29)
77% (8)
77%(1)
78%(14)
78% (8)
78%(4)
86%(66)
78%(35)
72%(8)
270 LVAD BLOOD STREAM INFECTION: THERAPEUTIC RATIONALE FOR TRANSPLANTATION R.S. Poston, D.N. Sorce, S. Husain, E.A. Stanford, S. Winowich, S. Kusne, B.P. Griffith, R.L. Kormos; University of Pittsburgh, Pittsburgh, PA, USA Blood stream infections (BSI) in VADpatients have a reportedly high mortality. UNOS currently grants 1a status to these patients, although reports of poor outcome following heart transplantation (HTrx) raises concerns about organ utilization. A predictor of mortality might be the inability to clear BSI prior to HTrx. Of the 146 patients who received a VAD implant, (1987-2000), 103 (71%) received a HTrx. The medical records of 21 (20%) with BSI prior to HTrx were retrospectively reviewed. Ten had definitive VAD infection (explanted pump cultures positive, Grp I), and 11 had only presumed VAD infection (bacteremia with negative pump cultures at explant Grp II). Grp I infection was associated with an 80% rate of persistent bacteremia at transplant with 30-day 1 year mortality rates of 20 and 40%, respectively. Grp II showed persistent bacteremia in 18% with a 30-day and 1 year mortality rate of 9% each. Grp I vs grp II patients had greater malnutrition (pre-VAD albumin 2.9⫹/-0.5 vs 3.3⫹/-0.8, p⬍0.05). The post-HTrx morbidity in Grp I was higher with longer post-HTrx intubation (9⫹/-11.2 vs. 3.6⫹/-5.5 days) and a greater rise in creatinine over the first postoperative week (1.5⫹/-1.0 vs. 0.22⫹/-0.3 mg/dl). No difference was seen in blood loss (2471⫹/-1310 vs. 2005⫹/-2548 cc), transfusion requirements (PRBC 1487⫹/-1012 vs. 1788⫹/-1701 cc; FFP 1714⫹/-1455 vs. 1333⫹/-1007; platelets 329⫹/-192 vs. 359⫹/-201 cc) or need for inotropic support. Although triple therapy (CSA/FK, prednisone, Imuran/Cellcept) was used in only 2/10 patients in Grp I vs. 6/11 in Grp II, there was no difference in the number of grade 2 or 3 rejections (0.45 vs. 0.91 events/year). Postoperative infections were common, but infection with the preoperative blood stream
Abstracts
268 NITRIC OXIDE INHALATION MODULATES ENDOTHELIN-1 AND BIG ENDOTHELIN-1 AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION F.D. Wagner1, S. Buz1, C. Knosalla1, M. Loebe1, R. Hetzer1, B. Hocher2; 1Deutsches Herzzentrum Berlin, Berlin, Germany; 2 Charite, Berlin, Germany Purpose: Nitric oxide inhalation therapy is now an established therapy in the treatment of right ventricular dysfunction due to pulmonary hypertension after left ventricular assist device (LVAD) implantation. Inhaled nitric oxide (iNO) decreases right ventricular afterload by its selective vasodilating effect on the pulmonary circulation. It is known that endothelin-1 (ET-1) contributes to pulmonary hypertension. The effects of iNO on circulating ET-1 and big endothelin (big ET-1) in LVAD-patients were investigated in this study. Methods: On weaning from cardiopulmonary bypass (CPB) 15 consecutive patients were treated with iNO because of right ventricular compromise secondary to pulmonary hypertension. Plasma ET-1 and big ET-1 concentrations were measured preoperatively, on CPB prior to iNO, 12, 24, and 48 hrs. postoperatively, as well as 72 hrs after cessation of iNO. Results: Mean initial iNO dose was 33 ppm (20-40 ppm). NO therapy was successfully weaned in all patients without a rebound phenomenon. ET-1 and big ET-1 were increased preoperatively (1.50 ⫹/- 1.9 and 3.87 ⫹/- 3.0 fmol/ml, respectively). ET-1 concentrations were highest on cardiopulmonary bypass (2.00⫹/1.56 fmol/ml). ET-1 and big ET-1 decreased significantly during iNO therapy and were lowest 72 hrs after cessation of iNO (Table 1). The iNO dose and plasma ET-1 levels correlated significantly (p⬍0.001). A significant correlation was also found between ET-1 and PA-pressures, PVR and PVR/SVR ratio, but not with CI and SVR. Conclusion: Since it is known, that ET-1 mediates pulmonary hypertension, we suggest a two-fold effect of iNO therapy: first a selective vasodilation of the pulmonary vasculature and second NO-mediated inhibition of one of the most potent vasoconstrictors of pulmonary vessels: ET-1. Table 1
ET-1 fmol/mL Big ET-1 fmol/mL
12h
24h
48h
72h post iNO
1.5⫹/-1.4 5.3⫹/-5.5
1.3⫹/-1.6 3.7⫹/-2.0
1.1⫹/-1.2 3.6⫹/-2.9
0.7⫹/-0.4 2.2⫹/-0.8
269 LVAD THERAPY IMPROVES UTILIZATION OF DONOR HEARTS: IMPLICATIONS FOR PROLONGED INOTROPIC THERAPY K. Aaronson, M. Eppinger, S. Wright, F.D. Pagani; University of Michigan, Ann Arbor, MI, USA Background: It is generally accepted that LVAD therapy improves post-transplant survival. However, the risk of LVAD implant generally discourages its use in favor of prolonged inotropic therapy. Methods: We investigated the impact of LVAD therapy on heart transplant outcomes in adult patients (age ⱖ 17 years) from January 1, 1995 to October 1, 2000. Sixty-two patients underwent LVAD implant as a bridge to transplant (TX). Survival (KM) for 50 patients with outcomes (death or TX) was calculated from the
241
time of LVAD implant or time of TX and compared to survival for 29 patients who underwent TX with inotropic therapy (UNOS status 1,1A,1B), and 82 who underwent TX as UNOS status 2. Results: TX survival in patients with prior LVAD support was superior compared to survival in patients undergoing TX as UNOS status 1 with inotropic therapy or as UNOS status 2 (see Table; ( ) - no. at risk). Survival from the time of LVAD implant (includes TX operation) was equivalent to survival for patients undergoing TX as UNOS status I with inotropic therapy. Conclusions: Long-term survival in patients undergoing LVAD therapy from the time of LVAD implant was equivalent to survival of patients undergoing TX as UNOS status 1 with inotropic therapy from the time of transplant. However, there were fewer transplant deaths in patients receiving LVAD therapy. LVAD therapy yields similar long-term survival with conservation of donor hearts. Given the critical shortage of donor organs, LVAD therapy as opposed to prolonged inotropic therapy may be preferential. Group
1 Year
3 Year
5 Year
Survival for Status 1 with LVAD from TX Survival for Status 1 with LVAD from LVAD Implant Survival for Status 1 with Inotropic therapy from TX Survival for Status 2 from TX
95%(31)
92% (6)
92%(1)
80%(29)
77% (8)
77%(1)
78%(14)
78% (8)
78%(4)
86%(66)
78%(35)
72%(8)
270 LVAD BLOOD STREAM INFECTION: THERAPEUTIC RATIONALE FOR TRANSPLANTATION R.S. Poston, D.N. Sorce, S. Husain, E.A. Stanford, S. Winowich, S. Kusne, B.P. Griffith, R.L. Kormos; University of Pittsburgh, Pittsburgh, PA, USA Blood stream infections (BSI) in VADpatients have a reportedly high mortality. UNOS currently grants 1a status to these patients, although reports of poor outcome following heart transplantation (HTrx) raises concerns about organ utilization. A predictor of mortality might be the inability to clear BSI prior to HTrx. Of the 146 patients who received a VAD implant, (1987-2000), 103 (71%) received a HTrx. The medical records of 21 (20%) with BSI prior to HTrx were retrospectively reviewed. Ten had definitive VAD infection (explanted pump cultures positive, Grp I), and 11 had only presumed VAD infection (bacteremia with negative pump cultures at explant Grp II). Grp I infection was associated with an 80% rate of persistent bacteremia at transplant with 30-day 1 year mortality rates of 20 and 40%, respectively. Grp II showed persistent bacteremia in 18% with a 30-day and 1 year mortality rate of 9% each. Grp I vs grp II patients had greater malnutrition (pre-VAD albumin 2.9⫹/-0.5 vs 3.3⫹/-0.8, p⬍0.05). The post-HTrx morbidity in Grp I was higher with longer post-HTrx intubation (9⫹/-11.2 vs. 3.6⫹/-5.5 days) and a greater rise in creatinine over the first postoperative week (1.5⫹/-1.0 vs. 0.22⫹/-0.3 mg/dl). No difference was seen in blood loss (2471⫹/-1310 vs. 2005⫹/-2548 cc), transfusion requirements (PRBC 1487⫹/-1012 vs. 1788⫹/-1701 cc; FFP 1714⫹/-1455 vs. 1333⫹/-1007; platelets 329⫹/-192 vs. 359⫹/-201 cc) or need for inotropic support. Although triple therapy (CSA/FK, prednisone, Imuran/Cellcept) was used in only 2/10 patients in Grp I vs. 6/11 in Grp II, there was no difference in the number of grade 2 or 3 rejections (0.45 vs. 0.91 events/year). Postoperative infections were common, but infection with the preoperative blood stream