Decreased Exercise Ventilatory Efficiency Is Associated with Central Sleep Apnea in Patients with Congestive Heart Failure

The 11th Annual Scientific Meeting echocardiography, antioxidant enzyme activities through superoxide dismutase (SOD) and catalase (CAT) and oxidative stress through carbonyl groups. Results: Ejection fraction (EF) decreased in MI group (59 6 6) vs S (71 6 2) (p ! 0.01) and was preserved in the MIT (62 6 9) vs ST (69 6 8). Antioxidant enzyme activity of SOD (U/mg protein) was not different among experimental groups S (9.0 6 1), MI (6.51 6 3.8), ST (10.63 6 2.32), MIT (6.0 6 3.6). CAT activity (pmol/mg protein) decreased in MI (33.87 6 6.39) vs S (73.01 6 19) (p ! 0.001) but it was up regulated in MIT group (38.73 6 8.1) vs ST (24.59 6 6.7). Protein damage assessed through carbonyl groups (nmol/mg protein) was not different among groups S (4 6 1.5), MI (3.7 6 1.7), ST (7.8 6 3.5), MIT (6.58 6 2.4). Conclusions: Unchanged cardiac function 48h post-experimental MI was associated with relative absence of oxidative injury. However, early decrease in CAT activity (less evident in MI animals receiving cells early post-MI) may signal later development of cardiac remodeling process through peroxide pathways, which could subsequently be quenched by cellular therapy.



HFSA

S91

Subject Characteristics Parameter Age (yrs) Gender (M/F) LVEF (%) NYHA Class Log AHI pVO2(ml) VE/VCO2 ETCO2 (mmHg)

CHF/CSA N 5 13

CHF/No CSA N 5 16

P-value

69 6 9 12/1 23 6 6 II-III 3.6 6 0.4 1418 6 473 41 6 9 31 6 7

61 6 10 8/8 30 6 7 II-III 1.3 6 1 1429 6 532 32 6 5 36 6 5

0.06 0.01 0.009 0.83 ! 0.001 0.95 0.002 0.05

059

057 Isolated Diastolic Dysfunction Vis-a-Vis HSCRP and Cardiorespiratory Fitness e DISCERN Study Arnold S. De Guzman1, Erlyn C. Demerre1, Mildred P. Luque1; 1Heart Institute, St. Luke’s Medical Center, Quezon City, Philippines Background: Chronic low-grade inflammation and endothelial dysfunction may be invoked to explain the impaired relaxation and stiffness of the contractile myocardium. Research into the histologic and ultrastructural mechanism of diastolic dysfunction is still lacking up to the present time. Data has proven the effect of systolic dysfunction on cardio-respiratory fitness; however, its relationship with diastolic dysfunction alone is relatively unclear. In this study, we determine the cross-sectional association of isolated diastolic dysfunction ‘‘face to face’’ with hsCRP and cardio-respiratory fitness. Method: Patients with 2 d echocardiography, treadmill exercise test, and plasma hsCRP as part of work up were reviewed and studied. Baseline characteristics between two groups were analyzed. Plasma hsCRP and Cardio-respiratory fitness were categorized. Isolated diastolic dysfunction is defined as those with echocardiographic evidence of left ventricular dysfunction of at least two indices with normal ejection fraction (O 50%). Results: Of the thirty nine patients who were included in the study, 20 (51.28%) had diastolic dysfunction. The mean age (56.03 6 12.18 years) was found to be significantly different between those with and without isolated diastolic dysfunction (P 5 0.048). Gender, Diabetes, Hypertension, and statin treatment were similar between groups. Plasma hsCRP classed as high-risk (n 5 27 $0.14 mg/dl) was significantly correlated with isolated diastolic dysfunction (P 5 0.029). Cardio-respiratory fitness (maximal oxygen uptake, ml/O2/kg/min) was not significantly correlated with isolated diastolic dysfunction (P 5 0.131). Conclusion: Our findings clearly support the hypothesis that endothelial dysfunction and inflammatory activity are involved in the pathogenesis of isolated diastolic dysfunction and have no association with the level of cardiorespiratory fitness. This novel information strongly supports the alteration in myocardial diastolic properties resulting from decrease endothelium-dependent vasomotor function brought about by the plasma levels of hsCRP promoting endothelial dysfunction and thereby contributing to its vicious cycle.

Hypothermia Attenuates Left Ventricular Remodeling and Preserved LV Function in Acute Myocardial Infarction Hoang Thai, Elizabeth Juneman, Tracy Hagerty, Hannah Raasch, Amir Kaki, Craig Peters, Reza Arsanjani, Rose Do, Jordan Lancaster, Mohamed Gaballa, Steven Goldman; 1Medicine, University of Arizona/SAVAHCS Medical Center, Tucson, AZ; 2Medicine, University of Arizona/SAVAHCS Medical Center, Tucson, AZ; 3 Medicine, University of Arizona, Tucson, AZ; 4Medicine, University of Arizona, Tucson, AZ; 5Medicine, University of Arizona, Tucson, AZ; 6Medicine, University of Arizona, Tucson, AZ; 7Medicine, University of Arizona, Tucson, AZ; 8 Medicine, SAVAHCS Medical Center, Tucson, AZ; 9Medicine, University of Arizona, Tucson, AZ; 10Medicine, University of Arizona/SAVAHCS Medical Center, Tucson, AZ Background: This study was designed to determine if induction of hypothermia immediately after acute myocardial infarction (MI) improves hemodynamic parameters, preserve left ventricular (LV) function and prevent LV remodeling. Methods: We ligated the left coronary artery of adult male Sprague-Dawley rats to induce MI. We then measured LV hemodynamics and assessed LV function and chamber dimensions by echocardiography immediately following MI and one hour after induction of hypothermia (temperature ! 28 C). A normothermic (temperature O 34 C) group of animals served as controls. Results: After MI and induction of hypothermia, the LV End Diastolic Pressure (LVEDP) was increased (P ! 0.05) in normothermic rats (22.2 6 4.4 mmHg) compared to hypothermic rats (10.7 6 1.6 mmHg). Similarly, LV systolic pressure in normothermic rats (109 6 4.4 mmHg) was higher (P ! 0.05) than hypothermic rats (86 6 2.4 mm Hg). There were no differences in LV dP/dt (4273 6 153 mmHg/sec vs 4575 6 457 mmHg/sec), the LV relaxation constant Tau trended towards a delay in hypothermic rats (36 6 6.3 msec) compared to in normothermic rats (25 6 2.3 msec). Hypothermia preserved LVEF compared to normothermia (58 6 5.0 vs. 37 6 3.3%, P ! 0.05). The displacement of the anterior infarcted region was normalized in the hypothermic animals (0.21 6 0.01 vs 0.05 6 0.02 cm, P ! 0.005). LV remodeling (LV systolic and diastolic chamber dilation) was also attenuated in the hypothermic animals. Conclusion: Induction of hypothermia after acute MI limits LV remodeling, preserved LV function and restored regional wall motion in the infarcted LV segment. These findings suggest that hypothermia may be a viable therapeutic option in the treatment of acute myocardial ischemic injury.

060 058 Decreased Exercise Ventilatory Efficiency Is Associated with Central Sleep Apnea in Patients with Congestive Heart Failure Lyle J. Olson1, Virend K. Somers1, Jennifer M. Miller1, Christopher G. Scott1, Michal S. Hoffmann1, Fatima H. Kuniyoshi1, Bruce D. Johnson1; 1Cardiovascular Diseases, Mayo Clinic, Rochester, MN Central sleep apnea (CSA) is frequently observed in patients with congestive heart failure (CHF). Hyperventilation may promote characteristic periodic breathing observed in CSA by driving arterial partial pressure of carbon dioxide (CO2) near or beyond the apneic threshold. Hyperventilation may also be observed during exercise in patients with CHF manifest by decreased ventilatory efficiency and low end-tidal CO2. Hypothesis. Hyperventilation with exercise is associated with CSA in patients with CHF. Methods. Patients (N 5 29) with CHF with LVEF ! 35% on optimal pharmacotherapy were enrolled as study subjects; all subjects underwent cardiopulmonary exercise testing and overnight laboratory-based polysomnography (PSG) for detection and quantification of severity of CSA. Severity of CSA was quantified by the apnea-hyponea index (AHI) measured at PSG. Ventilatory efficiency (VE/ VCO2) reported as the ratio of minute ventilation (VE) to carbon dioxide production (VCO2) and end-tidal CO2 (ETCO2) were measured at peak exercise. Results. See table. Linear regression also demonstrated high correlation between peak exercise VE/VCO2 (r 5 0.49;p 5 0.007) or ETCO2 (r 5 0.46;p 5 0.01) and the severity of CSA as quantified by AHI at PSG. Conclusion. In patients with CHF disordered ventilatory control characteristic of CSA may also manifest as hyperventilation and decreased ventilatory efficiency during exercise.

Location and Extent of Wall Motion Abnormality as Determinants of Systolic and Diastolic Remodeling Ian P. Clements1, David O. Hodge2, Christopher G. Scott3; 1Cardiovascular Diseases, Mayo Clinic, Rochester, MN; 2Biostatistics, Mayo Clinic, Rochester, MN; 3Health Sciences Research, Mayo Clinic, Rochester, MN Purpose: The respective roles of location and extent of regional wall motion abnormality (RWMA) on left ventricular (LV) systolic and diastolic remodeling in patients with RWMA and preserved LV ejection fraction (EF O 0.49) are unknown. Methods: LV end-systolic (ES), end-diastolic (ED) volume indices (VI, ml/m2), peak filling rate (PFR, ml/sec/m2) and location and extent of RWMA (using an eight segment LV model) were measured utilizing resting radionuclide angiograms in 140 patients (age $ 44 years) with LVEF O 0.49 and RWMA. A PFR value ! the 10th, between the 10th and 90th or O 90th percentile found in normal subjects was considered respectively to show delayed, normal or restrictive filling. Results: The location of RWMA occurred in the left anterior descending coronary distribution in 26 patients (LAD, mean number 6 SD abnormal segments 1.19 6 0.40), in 78 in the right or circumflex coronary (RCA þ CX, 1.60 6 0.61) and in 36 involved all three coronary artery distributions (LAD þ RCA þ CX, 3.03 6 0.94). LV EF and ESVI were similar in the three RWMA groups but EDVI and PFR were significantly greater in patients with LAD compared to RCA þ CX (p 5 0.03 and p 5 0.0004 respectively) and LAD þ RCA þ CX (p 5 0.04 and p ! 0.0001) RWMA (see Table). Multivariate analyses indicated that extent of RWMA was an independent predictor of LV EF and ESVI and location of RWMA independently predicted PFR. The filling pattern was significantly different (P 5 0.01) between LAD RWMA (15%, 58% and 27% respectively with delayed, normal and restrictive filling) and RCA þCX (39%, 52% and 9%) and LAD þ RCA þ CX (47%, 50% and 9%) RWMA; the extent