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Central Sleep Apnea in Patients with Heart Failure Is Associated with Restrictive Lung Function
The 9th Annual Scientific Meeting
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HFSA
S109
072
074
Influence of Acute Diastolic Dysfunction of LV End-Diastolic Pressure Mathew S. Maurer1, Ilan Hay1, Myung Jae Lee1, Geng-Hua Yi1, Anguo Gu1, Stefan Klotz1, Kenward Yu1, Kenny Tao1, Jie Wang1, Daniel Burkhoff1; 1Medicine, Columbia University, New York, NY
Central Sleep Apnea in Patients with Heart Failure Is Associated with Restrictive Lung Function Lyle J. Olson1, Virend K. Somers1, Angela J. Heydmann1, Tomas Kara1, Jiri Nykodym1, Kent R. Bailey1, Bruce D. Johnson1; 1Cardiovascular Diseases, Mayo Clinic, Rochester, MN
Background: Inccreases in ventricular diastolic stiffness are thought to result in elevated end diastolic pressure (EDP) in diastolic heart failure. Quantitative cardiovascular models suggest that increased chamber stiffness does not lead directly to increased LV EDP and, that EDP can increase with normal stiffness by expansion of intravascular volume even when LV function is normal. In order to evaluate these concepts, we tested whether 1) acute diastolic dysfunction leads directly to elevation of EDP and 2) whether EDP can be increased by volume loading despite normal systolic/diastolic function. Methods: Progressive diastolic dysfunction (DD) was induced in anesthetized open chest dogs by tightening of an elastic band (1cm width) placed around the LV. At each level of DD, end-systolic and end-diastolic pressurevolume relations (ESPVR and EDPVR) during inferior vena-cava occlusions were performed. In a second experiment, measurements were made after rapid volume infusion of 250, 500, 750 and 1000cc dextran. Results: Tightening of the band caused elevations of the EDPVR with chamber stiffness increasing from 0.04 ⫾ 0.002 to 0.08 ⫾ 0.017 ml-1 (p ⬍ 0.001) without significant effect on the ESPVR (p ⫽ NS, ANCOVA). Steady-state PV loops (Fig. A) showed a progressive shift towards lower volumes with little rise in EDP. Compared to baseline, a ∼50% increase in LV chamber stiffness caused only a ∼2 mmHg increase in EDP (p ⫽ NS) but a ∼9 ml decrease in EDV (p ⬍ 0.05). LV systolic pressure (BP) and stroke volume (SV) decreased. RV function was not compromised by LV banding. In contrast, volume expansion (Fig B) caused an increase in EDP (7 ⫾ 0.3 to 21 ⫾ 1.5mmHg at 1000mL, p ⬍ 0.005) with no significant change in the ESVPR/EDPVR. Conclusion: Acute isolated DD does not directly lead to elevated EDP, but rather results in reduced LV volume with concomitant reduction in BP and SV. In contrast, volume loading even with normal systolic/diastolic function lead to increased EDP. This is consistent with the concept that filling pressure is determined primarily by extra-cardiac factors and have implications for elucidating fundamental mechanisms of diastolic heart failure.
Heart failure (CHF) may cause restrictive lung function due to chronic congestion. Congestion also promotes lung J-receptor stimulation which increases ventilatory drive. Patients with CHF and central sleep apnea (CSA) have oscillatory ventilation with periods of hyperventilation alternating with hypoventilation/apnea. Hypothesis: Pts with CHF and CSA have more restrictive lung function compared to CHF pts without CSA. Methods: Consecutive CHF pts (n ⫽ 12) and controls (n ⫽ 13) were prospectively enrolled and studied by echocardiography (echo), laboratory polysomnography (PSG) and pulmonary function testing (PFT). PFT included forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). Controls were nonsmoking healthy subjects with no history of cardiac disease and on no cardioactive medications. Inclusion criteria for CHF pts included stable, optimized therapy, LVEF ⬍ 35% and sinus rhythm. PSG was used to diagnose and quantify central versus obstructive apneas or hypopneas. The apnea-hypopnea index (AHI) was defined as the frequency of apnea and hypopnea per hour of sleep. For comparison, CHF pts were grouped into those with CSA (AHI ⱖ 10) or no CSA (AHI ⬍ 10). Subjects with obstructive sleep apnea were excluded. Results: See Table; data summarized as mean and standard deviation. P-value P-value Controls CHF/no CSA CHF/CSA (CSA vs. (CHF vs. P-value (n ⫽ 13) (n ⫽ 7) (n ⫽ 5) no CSA) controls) (Anova) AHI 1.5 ⫾ 1.4 Age 50 ⫾ 14 Male gender 9(69%) BMI 26 ⫾ 3 LVEF 63 ⫾ 7 NYHA Class N/A FEV1 (%pred) 100 ⫾ 14 FVC (%pred) 102 ⫾ 14 98 ⫾ 8 FEV1/FVC (%pred)
3.4 ⫾ 3.2 61 ⫾ 9 3(43%) 28 ⫾ 3 29 ⫾ 7 2.0 ⫾ 1.0 98 ⫾ 11 101 ⫾ 9 98 ⫾ 7
36.8 ⫾ 24.2 70 ⫾ 12 5(100%) 26 ⫾ 3 22 ⫾ 6 2.0 ⫾ 1.2 78 ⫾ 5 81 ⫾ 7 96 ⫾ 5
N/A 0.24 0.08 0.29 0.09 0.99 0.008 0.007 0.08
N/A 0.006 0.89 0.68 ⬍0.001 N/A 0.02 0.02 0.65
N/A 0.02 0.11 0.49 ⬍0.001 N/A 0.005 0.005 0.88
p ⬍ 0.05 ⫽ significant; N/A ⫽ not applicable Linear regression analysis demonstrated a significant negative correlation between severity of CSA quantified by AHI and FVC (r ⫽ ⫺0.75; p ⫽ 0.04). Conclusion: Pts with CHF/CSA have more restrictive lung function than healthy controls or pts with CHF/no CSA. Restrictive lung function may reflect greater congestion in pts with CHF and CSA compared to controls and CHF/no CSA. Increased lung congestion may promote CSA in pts with CHF.
075
073 Resting Circulation Time as a Predictor of Exercise Capacity in Chronic Heart Failure Patients Norman R. Morris1, Kenneth C. Beck2, Eric M. Snyder2, Thomas P. Olson2, Lyle J. Olson2, Bruce D. Johnson2; 1School of Physiotherapy and Exercise Science, Griffith University, Gold Coast, Qld, Australia; 2Cardiovascular Diseases, Mayo Clinic, Rochester, MN The factors that predict exercise capacity in CHF are not well understood. It is clear that systolic factors such as ejection fraction (EF) are poor predictors of exercise capacity (VO2peak) in CHF. Recently some studies have suggested that other cardiovascular factors such as diastolic function and left ventricular stiffness may be better predictors of VO2peak. We have recently developed a method of measuring lung-tolung circulation time (circ time) using the reappearance of end tidal acetylene (PetC2H2) in the expired air following a single inhalation. This measure of circ time is not only dependent on cardiac function but also on blood flow distribution and thus may provide additional information on the cardiovascular impairment to exercise in CHF. We hypothesized that resting circ time may be a predictor of VO2peak in CHF, with longer resting circ times indicating poorer exercise capacity. Twenty-one CHF patients (age 58 ⫾ 2 yr, NYHA ⫽ 1.9 ⫾ 0.2; EF ⫽ 27.5 ⫾ 2.0 %, mean ⫾ SEM) participated in the study. Exercise capacity was determined using an incremental treadmill test, while resting circ time was measured using acetylene inhalation. The mean peak exercise capacity (VO2peak) for the CHF patients was 18.7 ⫾ 1.1 ml.kg-1.min-1 and the resting circ time was 53.7 ⫾ 1.8 s. Peak exercise capacity was strongly correlated with resting circ time (r ⫽ ⫺0.74, P ⬍ 0.01) and poorly correlated with EF (r ⫽ 0.11, p ⫽ ns). These results suggest that the measurement of resting lungto-lung circulation time may be a better predictor of exercise capacity in CHF than more traditional cardiovascular measures of systolic function. Funded by HL71478 and Heart Foundation Research Centre, Griffith University.
Identifying Right Ventricular Dysfunction with Tissue Doppler Imaging in Chronic Pulmonary Hypertension Navin Rajagopalan1, Kaoru Dohi1, Michael A. Mathier1, Srinivas Murali1, Angel Lopez-Candales1; 1Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA Background: Assessment of right ventricular function is problematic due to the complex structure and asymmetric shape of the right ventricle. Using tissue Doppler imaging to measure annular velocities has been shown to be useful in assessing global left and right ventricular function. Objective: To use tissue Doppler imaging (TDI) to identify the presence of right ventricular dysfunction in patients with chronic pulmonary hypertension. Methods: Nineteen patients (mean age 49 ⫾ 13; 14 female) with chronic pulmonary hypertension (PH) underwent standard transthoracic echocardiogram including TDI of both the lateral tricuspid (TA) and lateral mitral annuli (MA). Systolic (Sa) and early diastolic (Ea) annular velocites were measured from each position. All patients had a pulmonary artery (PA) systolic pressure ⬎ 50 mmHg. Etiology of PH included: primary 5, connective tissue disease 7, lung disease 3, and thromboembolic disease 4. Exclusion criteria included LV dysfunction, prosthetic valves, and pacemaker/ICD. Ten patients (mean age 44 ⫾ 15; 4 female) with normal biventricular function and normal PA pressures served as controls. RV fractional area change (RVFAC) was calculated in a blinded manner from the apical 4-chamber view to assess global RV function. Results: PH patients had a significantly lower Sa (7.3 ⫾ 2.0 vs 10.4 ⫾ 1.3 cm/s; p ⬍ 0.01) and Ea (6.3 ⫾ 2.7 vs 9.7 ⫾ 1.9 cm/s; p ⬍ 0.01) of the tricuspid annulus and a significantly lower Ea (6.7 ⫾ 2.3 vs 8.6 ⫾ 1.7 cm/s; p ⬍ 0.05) of the mitral annulus compared to controls. RVFAC was significantly lower in the PH patients as well (31 ⫾ 7 vs 48 ⫾ 5%; p ⬍ 0.01). There was a correlation found between TA Sa and RVFAC (r ⫽ 0.71). PH patients with RVFAC ⬍ 30% had a significantly lower TA Sa (5.6 ⫾ 1.3 vs 8.3 ⫾ 1.7 cm/s; p ⬍ 0.01) and TA Ea (4.1 ⫾ 1.2 vs 7.6 ⫾ 2.5 cm/s; p ⬍ 0.01) than PH patients with RVFAC ⱖ 30%. Conclusion: PH patients exhibit significant abnormalities of annular velocites at both the tricuspid and mitral positions compared to controls. Tricuspid annular velocities can aid in identifying PH patients with severe RV dysfunction.
•
HFSA
S109
072
074
Influence of Acute Diastolic Dysfunction of LV End-Diastolic Pressure Mathew S. Maurer1, Ilan Hay1, Myung Jae Lee1, Geng-Hua Yi1, Anguo Gu1, Stefan Klotz1, Kenward Yu1, Kenny Tao1, Jie Wang1, Daniel Burkhoff1; 1Medicine, Columbia University, New York, NY
Central Sleep Apnea in Patients with Heart Failure Is Associated with Restrictive Lung Function Lyle J. Olson1, Virend K. Somers1, Angela J. Heydmann1, Tomas Kara1, Jiri Nykodym1, Kent R. Bailey1, Bruce D. Johnson1; 1Cardiovascular Diseases, Mayo Clinic, Rochester, MN
Background: Inccreases in ventricular diastolic stiffness are thought to result in elevated end diastolic pressure (EDP) in diastolic heart failure. Quantitative cardiovascular models suggest that increased chamber stiffness does not lead directly to increased LV EDP and, that EDP can increase with normal stiffness by expansion of intravascular volume even when LV function is normal. In order to evaluate these concepts, we tested whether 1) acute diastolic dysfunction leads directly to elevation of EDP and 2) whether EDP can be increased by volume loading despite normal systolic/diastolic function. Methods: Progressive diastolic dysfunction (DD) was induced in anesthetized open chest dogs by tightening of an elastic band (1cm width) placed around the LV. At each level of DD, end-systolic and end-diastolic pressurevolume relations (ESPVR and EDPVR) during inferior vena-cava occlusions were performed. In a second experiment, measurements were made after rapid volume infusion of 250, 500, 750 and 1000cc dextran. Results: Tightening of the band caused elevations of the EDPVR with chamber stiffness increasing from 0.04 ⫾ 0.002 to 0.08 ⫾ 0.017 ml-1 (p ⬍ 0.001) without significant effect on the ESPVR (p ⫽ NS, ANCOVA). Steady-state PV loops (Fig. A) showed a progressive shift towards lower volumes with little rise in EDP. Compared to baseline, a ∼50% increase in LV chamber stiffness caused only a ∼2 mmHg increase in EDP (p ⫽ NS) but a ∼9 ml decrease in EDV (p ⬍ 0.05). LV systolic pressure (BP) and stroke volume (SV) decreased. RV function was not compromised by LV banding. In contrast, volume expansion (Fig B) caused an increase in EDP (7 ⫾ 0.3 to 21 ⫾ 1.5mmHg at 1000mL, p ⬍ 0.005) with no significant change in the ESVPR/EDPVR. Conclusion: Acute isolated DD does not directly lead to elevated EDP, but rather results in reduced LV volume with concomitant reduction in BP and SV. In contrast, volume loading even with normal systolic/diastolic function lead to increased EDP. This is consistent with the concept that filling pressure is determined primarily by extra-cardiac factors and have implications for elucidating fundamental mechanisms of diastolic heart failure.
Heart failure (CHF) may cause restrictive lung function due to chronic congestion. Congestion also promotes lung J-receptor stimulation which increases ventilatory drive. Patients with CHF and central sleep apnea (CSA) have oscillatory ventilation with periods of hyperventilation alternating with hypoventilation/apnea. Hypothesis: Pts with CHF and CSA have more restrictive lung function compared to CHF pts without CSA. Methods: Consecutive CHF pts (n ⫽ 12) and controls (n ⫽ 13) were prospectively enrolled and studied by echocardiography (echo), laboratory polysomnography (PSG) and pulmonary function testing (PFT). PFT included forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). Controls were nonsmoking healthy subjects with no history of cardiac disease and on no cardioactive medications. Inclusion criteria for CHF pts included stable, optimized therapy, LVEF ⬍ 35% and sinus rhythm. PSG was used to diagnose and quantify central versus obstructive apneas or hypopneas. The apnea-hypopnea index (AHI) was defined as the frequency of apnea and hypopnea per hour of sleep. For comparison, CHF pts were grouped into those with CSA (AHI ⱖ 10) or no CSA (AHI ⬍ 10). Subjects with obstructive sleep apnea were excluded. Results: See Table; data summarized as mean and standard deviation. P-value P-value Controls CHF/no CSA CHF/CSA (CSA vs. (CHF vs. P-value (n ⫽ 13) (n ⫽ 7) (n ⫽ 5) no CSA) controls) (Anova) AHI 1.5 ⫾ 1.4 Age 50 ⫾ 14 Male gender 9(69%) BMI 26 ⫾ 3 LVEF 63 ⫾ 7 NYHA Class N/A FEV1 (%pred) 100 ⫾ 14 FVC (%pred) 102 ⫾ 14 98 ⫾ 8 FEV1/FVC (%pred)
3.4 ⫾ 3.2 61 ⫾ 9 3(43%) 28 ⫾ 3 29 ⫾ 7 2.0 ⫾ 1.0 98 ⫾ 11 101 ⫾ 9 98 ⫾ 7
36.8 ⫾ 24.2 70 ⫾ 12 5(100%) 26 ⫾ 3 22 ⫾ 6 2.0 ⫾ 1.2 78 ⫾ 5 81 ⫾ 7 96 ⫾ 5
N/A 0.24 0.08 0.29 0.09 0.99 0.008 0.007 0.08
N/A 0.006 0.89 0.68 ⬍0.001 N/A 0.02 0.02 0.65
N/A 0.02 0.11 0.49 ⬍0.001 N/A 0.005 0.005 0.88
p ⬍ 0.05 ⫽ significant; N/A ⫽ not applicable Linear regression analysis demonstrated a significant negative correlation between severity of CSA quantified by AHI and FVC (r ⫽ ⫺0.75; p ⫽ 0.04). Conclusion: Pts with CHF/CSA have more restrictive lung function than healthy controls or pts with CHF/no CSA. Restrictive lung function may reflect greater congestion in pts with CHF and CSA compared to controls and CHF/no CSA. Increased lung congestion may promote CSA in pts with CHF.
075
073 Resting Circulation Time as a Predictor of Exercise Capacity in Chronic Heart Failure Patients Norman R. Morris1, Kenneth C. Beck2, Eric M. Snyder2, Thomas P. Olson2, Lyle J. Olson2, Bruce D. Johnson2; 1School of Physiotherapy and Exercise Science, Griffith University, Gold Coast, Qld, Australia; 2Cardiovascular Diseases, Mayo Clinic, Rochester, MN The factors that predict exercise capacity in CHF are not well understood. It is clear that systolic factors such as ejection fraction (EF) are poor predictors of exercise capacity (VO2peak) in CHF. Recently some studies have suggested that other cardiovascular factors such as diastolic function and left ventricular stiffness may be better predictors of VO2peak. We have recently developed a method of measuring lung-tolung circulation time (circ time) using the reappearance of end tidal acetylene (PetC2H2) in the expired air following a single inhalation. This measure of circ time is not only dependent on cardiac function but also on blood flow distribution and thus may provide additional information on the cardiovascular impairment to exercise in CHF. We hypothesized that resting circ time may be a predictor of VO2peak in CHF, with longer resting circ times indicating poorer exercise capacity. Twenty-one CHF patients (age 58 ⫾ 2 yr, NYHA ⫽ 1.9 ⫾ 0.2; EF ⫽ 27.5 ⫾ 2.0 %, mean ⫾ SEM) participated in the study. Exercise capacity was determined using an incremental treadmill test, while resting circ time was measured using acetylene inhalation. The mean peak exercise capacity (VO2peak) for the CHF patients was 18.7 ⫾ 1.1 ml.kg-1.min-1 and the resting circ time was 53.7 ⫾ 1.8 s. Peak exercise capacity was strongly correlated with resting circ time (r ⫽ ⫺0.74, P ⬍ 0.01) and poorly correlated with EF (r ⫽ 0.11, p ⫽ ns). These results suggest that the measurement of resting lungto-lung circulation time may be a better predictor of exercise capacity in CHF than more traditional cardiovascular measures of systolic function. Funded by HL71478 and Heart Foundation Research Centre, Griffith University.
Identifying Right Ventricular Dysfunction with Tissue Doppler Imaging in Chronic Pulmonary Hypertension Navin Rajagopalan1, Kaoru Dohi1, Michael A. Mathier1, Srinivas Murali1, Angel Lopez-Candales1; 1Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA Background: Assessment of right ventricular function is problematic due to the complex structure and asymmetric shape of the right ventricle. Using tissue Doppler imaging to measure annular velocities has been shown to be useful in assessing global left and right ventricular function. Objective: To use tissue Doppler imaging (TDI) to identify the presence of right ventricular dysfunction in patients with chronic pulmonary hypertension. Methods: Nineteen patients (mean age 49 ⫾ 13; 14 female) with chronic pulmonary hypertension (PH) underwent standard transthoracic echocardiogram including TDI of both the lateral tricuspid (TA) and lateral mitral annuli (MA). Systolic (Sa) and early diastolic (Ea) annular velocites were measured from each position. All patients had a pulmonary artery (PA) systolic pressure ⬎ 50 mmHg. Etiology of PH included: primary 5, connective tissue disease 7, lung disease 3, and thromboembolic disease 4. Exclusion criteria included LV dysfunction, prosthetic valves, and pacemaker/ICD. Ten patients (mean age 44 ⫾ 15; 4 female) with normal biventricular function and normal PA pressures served as controls. RV fractional area change (RVFAC) was calculated in a blinded manner from the apical 4-chamber view to assess global RV function. Results: PH patients had a significantly lower Sa (7.3 ⫾ 2.0 vs 10.4 ⫾ 1.3 cm/s; p ⬍ 0.01) and Ea (6.3 ⫾ 2.7 vs 9.7 ⫾ 1.9 cm/s; p ⬍ 0.01) of the tricuspid annulus and a significantly lower Ea (6.7 ⫾ 2.3 vs 8.6 ⫾ 1.7 cm/s; p ⬍ 0.05) of the mitral annulus compared to controls. RVFAC was significantly lower in the PH patients as well (31 ⫾ 7 vs 48 ⫾ 5%; p ⬍ 0.01). There was a correlation found between TA Sa and RVFAC (r ⫽ 0.71). PH patients with RVFAC ⬍ 30% had a significantly lower TA Sa (5.6 ⫾ 1.3 vs 8.3 ⫾ 1.7 cm/s; p ⬍ 0.01) and TA Ea (4.1 ⫾ 1.2 vs 7.6 ⫾ 2.5 cm/s; p ⬍ 0.01) than PH patients with RVFAC ⱖ 30%. Conclusion: PH patients exhibit significant abnormalities of annular velocites at both the tricuspid and mitral positions compared to controls. Tricuspid annular velocities can aid in identifying PH patients with severe RV dysfunction.