patients with heart failure (HF) by increasing atrial and ventricular contractility ... High Cardiac Output Is Correlated with Increased Myocardial Wall Stress and.
S96 Journal of Cardiac Failure Vol. 13 No. 6 Suppl. 2007 076 Dual Chamber Coupled Pacing Increases External Cardiac Work but Not Efficiency in Dogs with Ischemic Heart Failure Ruth N. Klepfer1, David E. Euler1; 1Medtronic, Inc., Minneapolis, MN Introduction: Dual chamber coupled pacing (DCCP) has potential as a therapy for patients with heart failure (HF) by increasing atrial and ventricular contractility and reducing the mechanical heart rate (MHR). Ventricular coupled pacing has been shown to improve cardiac efficiency in animal models of atrial fibrillation and LV dysfunction via high-dose isoflurane, but it has not been studied in an ischemic model of HF. We hypothesized that in an ischemic model of HF, we could apply DCCP with moderate rate support and improve cardiac efficiency. Methods: We compared the metabolic and hemodynamic effects of DCCP at 3 heart rates with normal sinus rhythm (NSR) in 8 anesthetized dogs with EF’s ! 35% from serial embolizations. A coupled stimulus was delivered to the right ventricle 10 ms after the effective refractory period. An atrial premature stimulus was delivered 60 ms prior to the ventricular stimulus. DCCP was applied with no atrial pacing (DCCP-low), with atrial pacing that increased the MHR by 5 bpm (DCCP-mid), and with atrial pacing that increased the MHR by 15 bpm (DCCP-high). Each setting was maintained for 15 minutes. There were 2 baselines in the protocol e one before and one after the DCCP steps. The two baselines were averaged to obtain a single baseline with which to compare the DCCP rates. The order of the DCCP rates was randomized. Left ventricular and aortic pressure, and aortic and total coronary flow were continuously measured. Arterial and coronary sinus samples were taken to measure blood gases. Results: DCCP at all rates significantly increased mean coronary flow (mCorFlow) (26%, 22%, 44% for low, mid and high respectively) and LVdPdtmax (125%, 120%, 117% respectively) and decreased MHR (-44%, -42%, -30% respectively). Only DCCP-high showed an increase in cardiac output (CO, 17 6 11%) and external cardiac work (CW, 19 6 21%) but this did not translate into a significant increase in efficiency due to the larger increase in mCorFlow (44% 6 48%). Conclusion: These results suggest that, unlike during atrial fibrillation or an isoflurane model of LV dysfunction, coupled pacing does not improve cardiac efficiency in an ischemic model of HF.
077 High Cardiac Output Is Correlated with Increased Myocardial Wall Stress and Brain Natriuretic Peptide in Patients with Chronic Kidney Disease on Hemodialysis S. van der Zee1, M. Spinelli1, Y. Noak2, D. Krauser1, B. Casazza2, A. Abdeldaim1, R.B. Devereux1, J. Silberzweig2, M. Farr1; 1Cardiology, Weill Cornell Medical College, New York, NY; 2Rogosin Kidney Center, Weill Cornell Medical College, New York, NY Background: Chronic volume overload and high arterio-venous fistula (AVF) flow contribute to CHF in the setting of CKD. An AVF increases cardiac output (CO), which can cause high-output heart failure. Case reports demonstrate reversal of CHF with AVF narrowing. The accepted ‘‘cut-off’’ for high AVF flow is O 2 L/ min or O 20-25% of CO, as measured at the AVF. The mechanism of myocardial dysfunction in the setting of high flow and high volume is poorly understood, but may be related to high myocardial sheer wall stress. Purpose: We prospectively evaluated 28 patients with CKD, but no history of CHF, who receive HD through an AVF. AVF flow (L/min) was measured with a transonic device, as was cardiac output (CO) (L/min) using reversal of AVF flow. Laboratory data and a transthoracic echocardiogram (TTE) were obtained. TTE measurements included ejection fraction (EF), LV mass, Tei index, end-systolic wall stress (ESS) and myocardial energy expenditure (MEE). The hypothesis was that patients with high AVF flow and high CO would have subclinical markers of myocardial dysfunction, increased myocardial wall stress and increased BNP, despite a normal EF. Results: Mean EF was low-normal (55 6 9%), but CO at the AVF was high-normal (6.0 6 1.6 L/min/m2) and correlated with CO measured by TTE (6.9 6 1.6 L/min/m2, r 5 0.8). Average AVF flow was 1.9 6 1 L/min, but AVF flow/CO was high (30 6 15%), as were Tei index (0.68 6 0.2) and BNP (540 6 830 pg/ml). LV mass index was high (128 6 27 g/m2) and mean decel. time was long (228 6 51 msec). Mean systolic BP was 132 6 28 mm Hg and Hgb 12.5 6 0.9 g/dl. Higher CO at the AVF was associated with higher BNP (p 5 0.028), greater access flow (p 5 0.035) and higher MEE (p 5 0.016). When the groups were partitioned between normal and high AVF flow/CO (percent flow ! 30% or $ 30%), we found significant differences in BNP (p 5 0.008), but not MEE (p 5 0.45).
Increased E/E0 ratio was not associated with high percent flow (p 5 0.45), but was associated with higher LVIDd (p 5 0.001), LVMI (p 5 0.006), ESS (p 5 0.034), MEE (p 5 0.003) and BNP (p 5 0.008). Conclusions: Patients with CKD have subclinical evidence of myocardial dysfunction, with increased myocardial wall stress, in part secondary to high CO. Longitudinal studies are needed to determine the role of high CO and AVF flow in developing CHF in CKD.
078 High Myocardial Tissue Copper Levels in Human Heart Failure Keith Youker1, Lindsey Rudloff1, Carlos Orrego1, Christian Kottner-Assad1, Guillermo Torre-Amione1; 1Cardiology, The Methodist DeBakey Heart Center, The Methodist Hospital, Houston, TX Objective: Previous studies of copper in heart failure demonstrate high serum levels in heart failure and demonstrated increased copper levels correlate with higher oneyear mortality and morbidity. To further understand the role of copper, we evaluated whether cardiac tissue demonstrated copper accumulation with heart failure (HF) in a murine model and in human failing myocardial tissues. Methods: Normal murine myocardium or HF murine myocardium induced by Ang II and a diet with high salt content were studied along with end stage human HF tissues (n 5 34) obtained at cardiac transplantation. Normal human controls (n 5 3) were obtained from donor hearts at implantation. Paraffin sections were prepared followed by reaction with sodium sulphide and TCA prior to staining with Timm’s reagent. Photomicrographs were analyzed using a semi-quantitative method with Image-Pro Plus to determine intensity of stain in a blinded fashion. Results: In the murine hearts we found increased copper expression in HF but not in controls (figure 1). Next we stained normal and human HF and found increased staining in HF myocardium and little or no staining in normal controls. The copper staining in a cohort of HF patients with nonischemic (n 5 10) and ischemic etiologies (n 5 10) showed no differences in the intensity. Finally, we compared staining intensity of failing myocardium from diabetic (n 5 10) and non-diabetic patients (n 5 4); we found the highest levels of copper staining in diabetic failing myocardium (figure 2). Conclusion: We demonstrate an association of HF and increased copper in a murine model of HF and in failing human myocardium. The human samples showed the highest levels of intra-myocardial copper in diabetic patients. This data supports the theory that copper may play an intimate role in HF and treatments used for chelating copper may prove beneficial to patients in HF.