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Insulin-Like Growth Factor-1 Signaling in Patients with Advanced Heart Failure
Abstracts Conclusions: Our data demonstrate adiponectin resistance in patients with HF and correction of systemic and local changes in adipose tissue and myocardium after mechanical unloading of the failing heart. These findings suggest a role of adipose tissue and its signaling molecules in the pathogenesis of advanced HF. 466 Ventricular Assist Device Implantation Corrects Systemic and Peripheral Impairment of Growth Hormone/Insulin-Like Growth Factor-1 Signaling in Patients with Advanced Heart Failure A. Chokshi,1 M. Chew,1 R.S. Khan,1 F. Cheema,2 M. Jones,1 H. Takayama,2 Y. Naka,2 D. Mancini,1 P.C. Schulze.1 1 Cardiology/Medicine, Columbia University Medical Center, New York, NY; 2Cardiothoracic Surgery, Columbia University Medical Center, New York, NY. Purpose: Patients with advanced heart failure (HF) develop muscle atrophy and dysfunction which has been linked to impaired growth hormone (GH)/insulin-like growth factor (IGF)-1 axis signaling and insulin resistance. We hypothesized that implantation of a ventricular assist device (VAD) will reverse GH/IGF-1 axis dysfunction in HF. Methods and Materials: Clinical data were obtained from medical records. Serum and myocardial tissue was obtained from controls and patients with HF undergoing VAD implantation and explantation. Rectus muscle tissue was obtained during VAD surgery. Serum levels of GH, IGF-1 and IGFBP-3 were measured by ELISA. Skeletal muscle mRNA expression was analyzed by RT-PCR. Grip strength measurements were performed serially. Results: Controls had a mean age of 46⫾3.8 yrs and BMI of 25.7⫾0.9 kg/m2. HF patients had a mean age of 55⫾13.4 yrs, ejection fraction of 18⫾5.5% and VAD duration of 177⫾145.8 days. Serum GH increased (647⫾382.2 pg/ml vs 1370.9⫾254.3 pg/ml in HF, p⫽0.15) while IGF-1 and IGFBP-3 decreased in HF (5867.7⫾1299.3 pg/ml vs 786.3⫾369.4 pg/ml in HF, p⬍0.05; 2912.6⫾326.6 ng/ml in con vs 1711.5⫾188.1 ng/ml in HF, p⬍0.05). After VAD, IGF-1 levels increased 4-fold (2678.2⫾750.9 pg/ml, p⬍0.05) and IGFBP-3 increased mildly (2085.5⫾205.4 pg/ml, p⫽0.14), without changes in elevated levels of GH. After mechanical unloading, local skeletal muscle tissue expression of IGF-1 and IGFBP-3 increased 35-fold and 6-fold (both p⬍0.05), and cardiac expression of IGF-1 increased 3-fold (p⬍0.05). Grip strength improved by 15% on VAD support (p⬍0.05). Conclusions: Our data demonstrate that hemodynamic improvement through VAD support leads to correction of growth hormone resistance, increased tissue expression of IGF-1 in skeletal muscle and myocardium and increased serum levels of IGF-1 in patients with advanced HF. These findings show the reversibility of metabolic abnormalities of impaired systemic and local GH/IGF-1 signaling in patients with advanced HF. 467 Generally Accessible Echocardiographic Parameters of Left Heart Could Predict Right Heart Failure after Left Ventricular Assist Device Implantation T.S. Kato,1 M. Farr,1 M. Maurer,1 H. Akashi,2 K. Shahzad,1 N. Gukasyan,1 M. Deng,1 S. Iwata,1 S. Homma,1 H. Takayama,2 Y. Naka,2 C.P. Schulze,1 U. Jorde,1 D. Mancini.1 1Department of Medicine, Division of Cardiology, Columbia University Medical Center, New York, NY; 2Department of Surgery, Division of Cardiothoracic Surgery, Columbia University Medical Center, New York, NY. Purpose: Right heart failure (RHF) after left ventricular assist device (LVAD) surgery is associated with high morbidity and mortality. Presurgery right heart evaluation by echocardiograms is often technically difficult. This study was designed to create a scoring system with echocardiogram (Echo) to assess the risk of RHF in LVAD recipients. Methods and Materials: We reviewed 111 patients (pts) who underwent LVAD surgery at Columbia University Medical Center after 2007. Pts with cardiogenic shock or post transplant graft failure were excluded. Echos within a month before the surgery were analyzed. RHF was
S159 defined as unexpected RVAD, inhaled nitric oxide (NO) ⬎48 hours, and/or inotropic support ⬎14 days. Results: 35 pts (32%) developed RHF; 15 with RVAD (14%), 17 with inotropes (15%) and 2 with NO (2%). Analyzable right heart images were obtainable from 56 pts (51%), while left heart images were obtained from all pts (100%). Thus, we focused on 2D left heart parameters. Left ventricular end-diastolic dimension (LVEDd) was smaller (62.7⫾10.2 vs. 73.2⫾12.7mm, p⬍0.0001), LV ejection fraction (LVEF) was greater (21.2⫾11.3 vs. 16.1⫾9.3%, p⫽0.0156), and the ratio of left atrium diameter (LAD) and LVEDd was greater (0.80⫾0.16 vs. 0.71⫾0.13, p⫽0.0037) in pts with RHF than those without RHF. The score was created based on ROC analysis of each parameter.[figure1]The sum of points ⬍2 excluded RHF with a sensitivity of 94% while ⱕ5 points determined RHF with a specificity of 92%.
Conclusions: Scoring system based on Echo-derived left heart parameter could predict RHF post LVAD surgery. Since this technique is not invasive or technically complicated, it may be utilized across centers. 468 Temporary Right Ventricular Support in Left Ventricular Assist Device Recipients A. Stepanenko,1 A. Loforte,2 N. Dranishnikov,1 E.V. Potapov,1 A. Montalto,2 M. Pasic,1 Y.-G. Weng,1 M. Dandel,1 H. Siniawski,1 M. Kukucka,1 T. Krabatsch,1 F. Musumeci,2 R. Hetzer.1 1Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; 2Department of Cardiac Surgery and Transplantation, San Camillo Hospital, Rome, Italy. Purpose: Right ventricular failure (RVF) remains a major early postoperative complication after left ventricular assist device (LVAD) placement despite attempts to identify pts at risk. We describe temporary right ventricular assist device (RVAD) support with CentriMag (Levitronix, Waltham, Mass.) after LVAD placement. Methods and Materials: In 02/2009-10/2010, 27 consec. adult pts (4 women; age 51.3 ⫾10.1, range: 25-69 years) with preop. evidence of RVF (as defined by Pennsylvania University score ⬎55 and Michigan University score ⬎5) received a temporary CentriMag RVAD at the time of implantation of rotary LVAD at our institutions. Pts were suffering from idiopathic DCM (n⫽12, 44.4%), ischemic cardiomyopathy (n⫽10, 37.03%) and valvular cardiomyopathy (n⫽5, 18.5%). In 22 pts the RVAD was inserted at the time of LVAD placement (primary placement). In 5 CentriMag was implanted within 48 hours after LVAD placement (secondary placement). Results: During daily echo examinations progressive improvement of RV function was documented in 20 (74.07%) pts (n⫽17, primary placement; n⫽3, secondary placement). After an average of 13.2 postop. days pts were weaned from CentriMag by reducing RVAD flow by 10% every 12h, and after an average of 17.1 postoperative days the RVAD was successfully removed. All pts had good systolic function of the RV (EF 38 – 40%), CVP of 10-15 mmHg and stable LVAD flow. 3 (11.1%) pts required permanent support with an implantable centrifugal RVAD (HeartWare Inc., Miramar, Fla.). Five (18.5%) pts died on temporary RVAD support. Overall 18 (66.6%) pts were discharged home (n⫽17, permanent LVAD support; n⫽1, permanent BVAD support) and 3 (11.1%) received successful transplantation.
S159 defined as unexpected RVAD, inhaled nitric oxide (NO) ⬎48 hours, and/or inotropic support ⬎14 days. Results: 35 pts (32%) developed RHF; 15 with RVAD (14%), 17 with inotropes (15%) and 2 with NO (2%). Analyzable right heart images were obtainable from 56 pts (51%), while left heart images were obtained from all pts (100%). Thus, we focused on 2D left heart parameters. Left ventricular end-diastolic dimension (LVEDd) was smaller (62.7⫾10.2 vs. 73.2⫾12.7mm, p⬍0.0001), LV ejection fraction (LVEF) was greater (21.2⫾11.3 vs. 16.1⫾9.3%, p⫽0.0156), and the ratio of left atrium diameter (LAD) and LVEDd was greater (0.80⫾0.16 vs. 0.71⫾0.13, p⫽0.0037) in pts with RHF than those without RHF. The score was created based on ROC analysis of each parameter.[figure1]The sum of points ⬍2 excluded RHF with a sensitivity of 94% while ⱕ5 points determined RHF with a specificity of 92%.
Conclusions: Scoring system based on Echo-derived left heart parameter could predict RHF post LVAD surgery. Since this technique is not invasive or technically complicated, it may be utilized across centers. 468 Temporary Right Ventricular Support in Left Ventricular Assist Device Recipients A. Stepanenko,1 A. Loforte,2 N. Dranishnikov,1 E.V. Potapov,1 A. Montalto,2 M. Pasic,1 Y.-G. Weng,1 M. Dandel,1 H. Siniawski,1 M. Kukucka,1 T. Krabatsch,1 F. Musumeci,2 R. Hetzer.1 1Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; 2Department of Cardiac Surgery and Transplantation, San Camillo Hospital, Rome, Italy. Purpose: Right ventricular failure (RVF) remains a major early postoperative complication after left ventricular assist device (LVAD) placement despite attempts to identify pts at risk. We describe temporary right ventricular assist device (RVAD) support with CentriMag (Levitronix, Waltham, Mass.) after LVAD placement. Methods and Materials: In 02/2009-10/2010, 27 consec. adult pts (4 women; age 51.3 ⫾10.1, range: 25-69 years) with preop. evidence of RVF (as defined by Pennsylvania University score ⬎55 and Michigan University score ⬎5) received a temporary CentriMag RVAD at the time of implantation of rotary LVAD at our institutions. Pts were suffering from idiopathic DCM (n⫽12, 44.4%), ischemic cardiomyopathy (n⫽10, 37.03%) and valvular cardiomyopathy (n⫽5, 18.5%). In 22 pts the RVAD was inserted at the time of LVAD placement (primary placement). In 5 CentriMag was implanted within 48 hours after LVAD placement (secondary placement). Results: During daily echo examinations progressive improvement of RV function was documented in 20 (74.07%) pts (n⫽17, primary placement; n⫽3, secondary placement). After an average of 13.2 postop. days pts were weaned from CentriMag by reducing RVAD flow by 10% every 12h, and after an average of 17.1 postoperative days the RVAD was successfully removed. All pts had good systolic function of the RV (EF 38 – 40%), CVP of 10-15 mmHg and stable LVAD flow. 3 (11.1%) pts required permanent support with an implantable centrifugal RVAD (HeartWare Inc., Miramar, Fla.). Five (18.5%) pts died on temporary RVAD support. Overall 18 (66.6%) pts were discharged home (n⫽17, permanent LVAD support; n⫽1, permanent BVAD support) and 3 (11.1%) received successful transplantation.