Cardiac Resynchronization Therapy Improves Pulmonary Function

The 12th Annual Scientific Meeting Table 1. VARIABLE

PRE-LVAD

POST-LVAD

p VALUE

Heart Rate (bpm) RA PA systolic PA diastolic PA mean (mmhg) PCWP (mmhg) CO (L/min) CI (L/min/M2) PA O2 saturation % TPG (mmhg) PVR (wood units)

89.8 6 24.9 13.8 6 5.3 60.6 6 12.3 25.4 6 6.4 39.8 6 7.4 25.6 6 8.8 4.7 6 2.1 2.3 6 1.0 49.2 6 14.4 14.2 6 7.3 3.2 6 1.7

76.3 6 15.3 5.9 6 3.1 33.7 6 10.2 11.9 6 4.5 20.2 6 4.5 11.4 6 6.4 6.3 6 1.3 3.2 6 0.7 62.3 6 5.3 8.8 6 5.8 1.4 6 0.9

0.2 !0.001* !0.001* !0.001* !0.001* 0.003* 0.05 0.04* 0.04* 0.047* 0.006*



HFSA

S47

criteria organs. For patients with cardiac amyloid, cardiac transplantation was followed by either high-dose chemotherapy and stem cell transplantation for patients with primary (AL) or by orthotopic liver transplantation for TTR amyloidosis. Results: Of the 18 patients with systemic amyloidosis and heart failure 13 had AL amyloid, 4 had TTR amyloid and one had senile cardiac amyloidosis. Amyloid heart transplant recipients did not differ from non-amyloid transplant recipients in age (55 6 8 vs.52 6 12, p 5 0.10), but were more often female (44% vs. 22%, p 5 0.04) and more often received non-blood type O donor organs (83% vs. 65%, p 5 0.055) than patients with non-amyloid indications. Survival (shown below) was reduced among the amyloid patients compared to standard criteria patients (p ! 0.001 by log rank) but did not differ from the other high risk transplant patients (p 5 NS). Conclusions: Cardiac transplantation for amyloid patients with extendeddonor criteria organs is associated with an intermediate-term survival post-transplant that is comparable to other extended-donor transplant patients at our institution but is lower than that of contemporaneous standard criteria heart transplant patients.

Conclusion: Chronic unloading of the left ventricle with an axial flow LVAD consistently reverses severe PH that is refractory to medical therapy in potential TX candidates. Based on our experience, implantation of an axial flow LVAD should be considered standard of care in these challenging patients.

146 Survival in Pediatric Myocarditis with Successful Bridge to Recovery or Orthotopic Heart Transplantation by Mechanical Circulatory Support John L. Jefferies1, Jack F. Price1, Charles D. Fraser2, Jeffrey J. Kim1, Susan W. Denfield1, William J. Dreyer1, David L.S. Morales2, Jeffrey A. Towbin1; 1Pediatric Cardiology, Baylor College of Medicine, Houston, TX; 2Congenital Heart Surgery, Baylor College of Medicine, Houston, TX Background: Acute viral myocarditis in children can result in severely decompensated heart failure and significant mortality. Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) offer a life-saving treatment strategy in patients refractory to optimal medical therapies. Successful bridge to recovery or orthotopic heart transplantation (OHT) has been reported with multiple devices in adult populations but limited data exists in the pediatric population. We report our single institutional experience with use of mechical circulatory support in myocarditis. Methods: A retrospective analysis of all patients at Texas Children’s Hospital undergoing surgical implantation of mechanical circulatory support devices including VADs and ECMO from 1995 to 2007 was performed. Results of viral testing for myocarditis including blood analysis and endomyocardial biopsy (EMB) were reviewed. Results: 96 successful implantations were performed in 93 children. Of these, 12 patients were identified that carried the diagnosis of myocarditis. Two of these patients had device changes during the course of therapy yielding a total of 14 device implantations. Presenting symptoms included: fatigue (7/12), chest pain (2/12), abdominal pain (2/12), and upper respiratory symptoms (1/12). Types of device therapy included: Biomedicus LVAD (5/14), DeBakey MicroMed (2/14), Thoratec LVAD (1/14), Berlin EXCOR LVAD (2/14), and ECMO (4/14). Mean age at implantation was 6.3 years (SD 6 4.6 years) and mean weight was 20.8 kg (SD 6 13.3 kg). Mean duration of device therapy was 13.4 days. Total time of mechanical support was 202 days.10/12 patients survived to discharge with 5 undergoing successful OHT. The remaining 5 patients recovered cardiac function and were successfully weaned off of mechanical support. Four patients had positive PCR for parvovirus-B19 (3 by EMB;1 by blood analysis). Assessment of left ventricular function by ejection fraction were made pre- and post-assist which revealed significant improvement (15% vs 51%; p 5 0.02). Conclusions: Mechanical circulatory support is a viable treatment strategy in pediatric patients with acute myocarditis over a wide range of patient weights and ages. Successful bridge to recovery or OHT is seen in the majority of pediatric patients with myocarditis.

147 Survival in Cardiac Amyloid Using Extended Donor Organs in Comparison to Transplantation for Other Indications Joseph A. Radojevic1, Rachel Bijou1, Paolo Colombo1, Mario Deng1, Ronald Drusin1, Evelyn Horn1, Sun Hi Lee1, Yoshifumi Naka2, Susan Restaino1, Donna Mancini1, Mathew S. Maurer1; 1Medicine, Division of Cardiology, Columbia Univeristy Medical Center, New York, NY; 2Surgery, Division of Cardiothoracic Surgery, Columbia University Medical Canter, New York, NY Background: Cardiac amyloidosis complicated by heart failure has a high mortality. Heart transplantation (OHT) for patients with amyloidosis is controversial due to recurrence of disease in the transplanted organ or progression of disease in other organs. Short term survival is similar to patients receiving OHT for other indications at our institution; however the long term outcome is unclear. Methods: Patients with cardiac amyloidosis and heart failure who underwent OHT at our institution (n 5 18) were compared in terms of survival to a cohort of patients undergoing OHT for standard (n 5 580) or high risk (n 5 62) indications during 2001e2007. Both patients with cardiac amyloid and high risk OHT received extended-donor

148 Outcomes in Patients with Adriamycin Cardiotoxicity Undergoing Orthotopic Heart Transplantation: An Analysis of the UNOS Database Cheri A. Silverstein1, Douglas B. Sawyer1; 1Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN Background: Anthracyclines are the mainstay of treatment for breast cancer, leukemia, lymphoma and sarcomas. Doxorubicin (AdriamycinÒ), the first and most widely used anthracycline, was approved in 1974, and, since then, cardiac toxicity has remained the major complication of use of these drugs. The toxicity follows a dose response relationship, with dilated cardiomyopathy and heart failure rates rising rapidly at cumulative doses O than 550 mg/m2. Orthotopic heart transplant (OHT) has been considered an option for cancer survivors considered in complete remission; however, to our knowledge, the incidence and outcomes of OHT among these patients has not been reported. Methods: We reviewed the United Network for Organ Sharing (UNOS) dataset to identify individuals waitlisted and transplants performed between October 1987 and March 2007. Individuals were stratified between primary diagnosis of Dilated Myopathy: Adriamycin and any other diagnosis. The subset performed from 1995 to 2005 was reviewed for survival rate at 12, 36, 60 and 120 months post-transplant. Results: Between October 1987 and March 2007, 67,170 individuals were waitlisted for OHT. Of those, 464, or 0.69%, had a primary diagnosis of Dilated Myopathy: Adriamycin. In that same period, 41,778 individuals received OHT. Of those, 308, or 0.74%, had a primary diagnosis of Dilated Myopathy: Adriamycin. In the subset from 1995e2005, survival rate at 12 months was 83.83% [78.10e89.56] in the adriamycin group and 85.80% [85.35e86.25] in all others. Survival rate at 36 months was 76.39% [69.69e83.09] in the adriamycin group and 78.52% [77.98e79.06] in all others. Survival rate at 60 months was 69.97% [62.41e77.53] in the adriamycin group and 71.93% [71.31e72.55] in all others. Survival rate at 120 months was 63.57% [54.65e72.48] in the adriamycin group and 52.22% [51.21e53.23] in all others. Conclusions: Individuals with a primary diagnosis of Dilated Myopathy: Adriamycin accounted for 0.7% of all patients waitlisted for and receiving OHT between October 1987 and March 2007. Survival for individuals with Dilated Myopathy: Adriamycin is equivalent to survival for individuals with all other diagnoses at 12, 36, and 60 months, but survival at 120 months is higher in individuals with Dilated Myopathy: Adriamycin, which is likely a reflection of the younger mean age of this population.

S48 Journal of Cardiac Failure Vol. 14 No. 6S Suppl. 2008 149

151

Cardiac Resynchronization Therapy Improves Pulmonary Function Andrew D. Calvin1, Bruce D. Johnson1, Robert F. Rea1, Jennifer M. Miller1, Lyle J. Olson1; 1Mayo Clinic, Rochester, MN

Improved Response to Cardiac Resynchronization Therapy through Delay Optimization Using Acoustic Cardiography Versus Doppler Echocardiography Stefan Toggweiler1, Markus Roos1, Michel Zuber1, Richard Kobza1, Peiman Jamshidi1, Paul Erne1; 1Division of Cardiology, Kantonsspital, Luzern, Switzerland

Heart failure (HF) causes abnormalities of pulmonary mechanics and gas exchange including restrictive lung function and diffusion abnormalities due to congestion. Cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF), lowers LV filling and pulmonary artery pressures, and reduces mitral regurgitation which may each decrease pulmonary congestion. Hypothesis: CRT promotes improved pulmonary function. Methods: Ambulatory HF patients (n 5 22) meeting standard guidelines for CRT implant were prospectively enrolled. Pulmonary function and exercise testing with metabolic gas exchange were performed before and 6 months after CRT. Pulmonary function measures included vital capacity (VC), forced expiratory volume at one second (FEV1) and diffusing capacity for carbon monoxide (DLCO) reported as percent (%) predicted. Exercise measures included peak oxygen uptake (pVO2, ml/kg/min) and 6 minute walk (mw, meters). Characteristics including NYHA class, Minnesota Living with Heart Failure (MLWHF) Questionnaire score, QRS duration (ms) and LVEF (%) were recorded. Pre and post-CRT measures were compared by paired t-test (see Table). Simple linear regression was used to evaluate the relationship between continuous variables (p ! 0.05 considered significant). Results: Changes in 6 mw (380 to 392; p 5 0.62), pVO2 (13.2 to 13.6; p 5 0.64) and DLCO (67% to 66%; p 5 0.55) were non-significant. Increase of FEV1 correlated with both the degree of QRS prolongation (p 5 0.03, r 5 0.48) and LVEF depression (p 5 0.05, r 5 0.42) at baseline. n 5 22

MLWHF

NYHA

LVEF (%)

QRS (ms)

VC (%)

FEV1(%)

Pre-CRT Post-CRT p value

49 31 !0.01

3.0 1.9 !0.01

25 35 0.01

175 164 0.03

82 86 0.04

76 81 0.03

Introduction: The use of cardiac resynchronization therapy (CRT) is an effective treatment for heart failure, and studies have demonstrated that optimization of device settings leads to superior outcomes. Acoustic cardiography has recently been shown to produce systolic time intervals that correlate well with measures of left ventricular contractility. Hypothesis: Optimization of atrio-ventricular (AV) and inter-ventricular (VV) delays in CRT by acoustic cardiography and Doppler echocardiography based on displacement imaging leads to clinical and functional improvements. Methods: In 19 patients with a CRT device (17 male, mean age 64 6 8 years, 13 6 7 months post implant) hemodynamic and clinical performance were measured using spiroergometry, 2D/3D echocardiography at baseline and 6 weeks post delay optimization. Optimal delays were determined through acoustic cardiography using the lowest electromechanical activation time (EMAT, time from Q onset to the S1), and through Doppler echocardiography, using the shortest time difference to peak systolic contraction in the septal and posterolateral wall. Patients were crossed over between the two optimization methods 6 weeks post initial optimization. 11 patients were optimized with acoustic cardiography first. Results: Delay optimization with acoustic cardiography significantly improved work capacity by 4.1%, maximum oxygen uptake by 8.1%, and oxygen pulse (maximum oxygen uptake divided by heart rate) by 8.1%. Ejection fraction improved by 18.3% versus the baseline AV and VV delays. Optimization with displacement imaging yielded a 16.9% significant relative increase in ejection fraction without any significant changes in spiroergometric parameters. Conclusion: Digital acoustic cardiography for AV and VV optimization yields a significant improvement in clinical and hemodynamic parameters, surpassing optimization with Doppler echocardiography based displacement imaging.

Conclusion: CRT improves restrictive lung function in patients with HF; the benefit appears greatest among individuals with the widest QRS and lowest LVEF at baseline. Lack of change of DLCO suggests that HF may be associated with altered alveolar-capillary membrane function not reversible by CRT. Improved pulmonary function post-CRT may be due to decreased congestion which may contribute to improved NYHA class and MLWHF score.

150 Improved Cardiac Structure and Function in Early-Stage Heart Failure with Chronic Treatment Using an Implantable Device: Results from European and United States Trials of the RheosÒ System John D. Bisognano1, Peter de Leeuw2, David S. Bach3, Eric G. Lovett4; 1Cardiology, University of Rochester, Rochester, NY; 2Internal Medicine, University Hospital Maastricht, Maastricht, Netherlands; 3Internal Medicine, University of Michigan, Ann Arbor, MI; 4Research, CVRx, Inc., Minneapolis, MN Background: Cardiac structure and function are abnormal in heart failure (HF). Rheos Therapy reduces blood pressure (BP) in patients with hypertension (HTN) and improves left ventricular (LV) structure and systolic function in a canine HF model. It is unknown if Rheos Therapy improves cardiac structure and function in patients. Methods: Stage A-B HF (stage II HTN) subjects (systolic BP $ 160 mmHg) taking $3 anti-HTN drugs ($1 diuretic) were implanted with the Rheos System. Baseline data were acquired before implant. The Rheos System was activated 1 month after implant. Follow-up occurred after 3 and 12 months of therapy. Echocardiograms were reviewed at a blinded core lab. Changes at follow-up versus baseline were analyzed with paired t-tests for all subjects with echocardiograms available at baseline and 12 months. Results: 18 subjects (12 Europe/6 US, 8 M/10 F, Age 49.7 6 11.0 yr, BMI 33.7 6 7.5 kg/m2, 14 with LV hypertrophy) were implanted at 5 centers. The Rheos System improved cardiac structure and function while reducing BP. Heart rate did not change. No unanticipated adverse events occurred. Conclusions: Chronic Rheos Therapy in early-stage HF patients remodels cardiac structure and improves function while reducing BP. Benefits are incremental to those achieved with aggressive medical therapy. Further study is needed to assess potential benefit of Rheos Therapy in advanced HF. Change in Cardiac Structure & Function, BP, and Medication (N 5 18) Baseline

D 3 Months

D 12 Months

LV Mass Index (g/m2) 132.8 6 33.3 e15.7 6 13.7z e25.0 6 18.2z Left Atrial Dimension (mm) 44.1 6 8.1 e1.0 6 3.6 e2.4 6 3.5* Mitral E Wave Velocity (cm/s) 85 6 19 e6 6 14 e5 6 14 Mitral A Wave Velocity (cm/s) 83 6 22 e6 6 13 e10 6 13y LV End Diastolic Dimension (mm) 50.6 6 5.3 e1.0 6 2.6 e1.8 6 2.6* LV End Systolic Dimension (mm) 32.6 6 5.0 e1.8 6 3.4  e2.9 6 4.9  Midwall Fractional Shortening (%) 13.9 6 3.5 +1.1 6 2.6 +1.7 6 2.9  Office Cuff Systolic BP (mmHg) 181.3 6 24.8 e25.0 6 25.7z e29.3 6 24.9z Office Cuff Diastolic BP (mmHg) 107.0 6 18.3 e12.6 6 19.6* e14.9 6 20.1* Anti-HTN Medications (#) 5.2 6 1.9 e0.3 6 1.9 e0.6 6 0.8* Values: mean 6 SD  p ! 0.05 *p # 0.01 yp # 0.005 zp ! 0.001

152 Clinical Significance of Mitral Regurgitation Following Left Ventricular Assist Device Implantation Sarinya Puwanant1, James A. Hill1, Charles T. Klodell2, Karen K. Hamilton1, Richard S. Schofield1, Timothy S. Cleeton1, Daniel F. Pauly1, Juan M. Aranda, Jr.1; 1Cardiovascular Medicine, University of Florida, Gainesville, FL; 2 Cardiothoracic Surgery, University of Florida, Gainesville, FL Objectives: 1) To study the change in the mitral regurgitation (MR) after left ventricular assist device (LVAD) implantation. 2) To assess the impact of residual MR on LVAD- related adverse outcomes and mortality. Methods: Echo and clinical outcomes in 33 consecutive patients (Pts) (age 54 6 13) with LVAD were evaluated. Significant (SIG) MR was defined as $moderate MR. Post operative adverse outcome (POAO) was present if 1 of the followings occurred post LVAD; stroke, arrhythmia, LVAD malfunction, organ failure, or subsequent RVAD need. We excluded tamponade and infection for POAO. Results: Pre-op MR was present in 79 % (26/33); 30% 5 mild; 36% 5 moderate; 13% 5 severe. After (28 6 40 days) LVAD implant, residual MR was present in 33 % (11 / 33); 21% 5 mild; 9% 5 moderate; 3% 5 severe. Of 33 Pts, 22 (67%) had a reduction of at least 1 grade of MR post LVAD and 2 (6%) had worsening MR. Post op SIG MR is not different between Pts with and without MV repair (2/7 (29%) vs. 2/24 (7%), p 5 0.17) at the time of LVAD implant. None (0/15) of Pts with pulsatile LVAD had post op SIG MR whereas 22% (4/18) of patients with axial flow LVAD had post op SIG MR (p 5 0.02). Of 33 Pts, 9 (27%) Pts died post LVAD (89 6 68 days); 6 died from POAO related causes; 3 died from infection and lung cancer. Of 33 Pts, 16 (48%) had POAO and 19 (58%) had combined endpoints of POAO / death. Of 33 Pts, 11 (33%) had no reduction ($1 grade) in MR post LVAD. These Pts had a SIG higher POAO [73% (8/11) vs 36% (8/22), p 5 0.046] and combined endpoints of POAO/death [82% (9/11) vs 46% (10/22), p 5 0.039].