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Does Atrial Fibrillation Affect Outcomes in Patients Admitted With Acute Heart Failure? Insights From the Ascend-Hf Trial
Abstracts
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highly-trained male athletes in order to characterize atrial function across a broader range of exercise intensities. We hypothesized that LA filling improves acutely during lightintensity exercise due to enhanced atrioventricular-plane displacement (AVPD) during LV systole, and that reduced diastolic filling time at moderate exercise intensities limits passive LA emptying and increases LA active emptying volume. METHODS: Ten healthy endurance-trained males (mean age ¼ 54 4 years) were studied at rest and during cycle-ergometry at light (w100 b/min, LE) and moderate (w130 b/min ME) intensity exercise. Doppler echocardiography was used to assess coupling and diastolic function. LA and LV volumes were measured using Simpson's method from 2D greyscale images in standard apical windows. AVPD was analyzed by tissue-tracking Doppler echocardiography. Simultaneous right heart catheterization was performed to measure hemodynamics, including pulmonary capillary wedge pressure (PCWP). RESULTS: Echocardiographic data was available from all subjects, with hemodynamic data available from 6 subjects; data is presented in Table 1. LV EDV increased from rest to LE and then to ME. During LV systole, AVPD increased from rest to LE, but did not increase further at ME. LA reservoir volume increased modestly from rest to LE, and remained constant. In contrast, during LV diastole, LA conduit volume increased during LE, and increased further at ME. LA active emptying volume increased from rest only at ME. PCWP increased acutely during LE, with partial normalization occurring during ME. CONCLUSION: AVPD, and thus the longitudinal component of LV systole, contributes to LA filling primarily during LE, but is a limited mechanism beyond LE. LA phasic function appears to shift from reliance on AVPD to an increase in conduit function and active emptying to maintain and increase LV EDV during ME. As LA reservoir volume remained stable from LE to ME, despite a decline in PCWP, this suggests possibly altered LA compliance during exercise.
149 DOES ATRIAL FIBRILLATION AFFECT OUTCOMES IN PATIENTS ADMITTED WITH ACUTE HEART FAILURE? INSIGHTS FROM THE ASCEND-HF TRIAL S Abualnaja, M Podder, AF Hernandez, JJ McMurray, PW Armstrong, JA Ezekowitz Edmonton, Alberta BACKROUND:
Acute heart failure (AHF) is a major cause of morbidity and mortality and commonly associated with atrial fibrillation (AF). Such patients are thought to be more symptomatic during admission, have higher heart rates at admission and discharge and poorer long term outcomes than patients in sinus rhythm. The basis for these assumptions are unsubstantiated. METHODS: AHF patients (n¼7007) enrolled in the ASCEND-HF trial were included. Details on heart rate (HR) and other clinical variables (including pre-existing or new onset AF) were collected on the case report form. Unadjusted and adjusted outcomes (using the ASCEND-HF multivariable model) are presented for 30-day and 180-days. RESULTS: There were 61.8% (n¼4330) patients in sinus rhythm and 38.2% (n¼2677) had AF. Patients with AF were older (72 vs. 63 years), more often smokers and had more comorbidities such as hypertension, and vascular disease. Patients with AHF and AF had a lower median BNP on admission than patients without AF (945 vs. 1040 pg/ml, p¼0.018) and higher median left ventricular ejection fraction (31% vs. 27%, p<0.001). Patients with vs. those without AF had similar ventricular rates on admission (81 vs. 83 bpm, p¼0.14) but were lower at discharge (74 vs. 78 bpm, p<0.001; Figure). Patients with AF did not differ with respect to the moderate or marked improvement in dyspnea at 6h or 24h (p 0.09). Patients with AF had higher unadjusted 30-day mortality/HF rehospitalization (11.6% vs. 8.6%, p<0.001) and 31 to 180-day mortality (11.1% vs. 8%, p<0.001) rates compared to patients without AF (Table). After adjustment, AF remained an independent predictor for worse clinical outcomes. CONCLUSION: Among patient admitted to the hospital with AHF, AF is associated with higher morbidity and mortality at 30-day and 180-day compared to those not in AF. AF remains an independent predictor, despite a well controlled ventricular rate.
Rest and exercise data Rest LV EDV (mL) AVPD (mm) LA Reservoir vol. (mL) LA Conduit vol. (mL)
117 ± 12 14 ± 1 33 ± 8 40 ± 8
Light Ex.
Moderate Ex. 129 ± 14
18 ± 2
**
17 ± 3‡
30 day all-cause mortality
41 ± 9
**
‡
126 ± 12
‡†
40 ± 8 *
‡†
46 ± 10
56 ±12
LA Active Empty. vol.(mL) 12 ± 4
16 ± 5
24 ± 9‡†
Mean PCWP (mmHg)
20 ± 2**
15 ± 5‡†
11 ± 3
Short and long-term outcomes Outcome N (%)
**
* p < 0.05, LE vs. Rest; ** p < 0.01, LE vs. Rest; ‡ p < 0.05, ME vs. Rest; † p < 0.05, ME vs. LE
All patients (N=7007)
HF without AF HF with AF Unadjusted Adjusted Odds* or (N=4330) (N=2677) p-value Hazard** ratio (95% CI)
267 (3.8)
143 (3.3)
124 (4.6)
0.005
1.20* (0.91 - 1.58)
30 day mortality or 666 (9.7) HF-rehosp
362 (8.6)
304 (11.6)
<0.001
1.20** (1.00 - 1.45)
31 to 180-day mortality
329 (8.0)
280 (11.1)
<0.001
1.16** (0.93 - 1.43)
609 (9.2)
*Odds Ratio, adjusted for ASCEND-HF 30-day all-cause-mortality model (age, blood urea nitrogen, serum sodium, baseline dyspnea, systolic blood pressure). **Hazard Ratio, adjusted for ASCEND-HF 30-day mortality/HF-readmission and 31 to 180-day mortality model (age, blood urea nitrogen, baseline sodium, creatinine and systolic blood pressure, history of cerebrovascular disease, depression, HF-hospitalization, qualifying episode of dyspnea and JVP).
S148
Canadian Journal of Cardiology Volume 29 2013
Johnson & Johnson 150 REPETITIVE OSA PROMOTES ATRIAL FIBRILLATION BY IMPAIRING ATRIAL CONDUCTION F Xiong, T Kato, Y Iwasaki, A Maguy, P Comtois, S Nattel Montréal, Québec BACKGROUND:
Patients with repetitive obstructive sleep apnea (OSA) have increased risks of developing atrial fibrillation (AF), but the mechanisms are poorly defined. In this work, we tested the hypothesis that long term repetitive OSA causes atrial structural remodeling and promotes AF by interfering with atrial conduction. METHODS: Twenty-week-old male rats were intubated and ventilated with air and 2% isoflurane. Repetitive OSA was mimicked by repetitive 2-min cycles (airway obstructed for 40 s/ 80 s recovery) 20 times daily, 5 days/week for 4 weeks. Non-OSA controls had the same procedure without obstruction. Fibrous tissue content and Cx43 expression were assessed by histomorphometry. Optical mapping (di-4ANEPPS) with blebbistatin for mechanical uncoupling was used to study impulse propagation. RESULTS: After 4 weeks of repeated OSA/nonOSA, AF was induced in 7 of 9 (78%) long term OSA rats vs 2 of 9 (22%) long term non-OSA rats (P<0.05). LA fibrous tissue content was greater in OSA (5.30.7% of cross sectional area) than non-OSA (3.70.5%, P<0.05). Cx43 expression was reduced by 55% in OSA and extensive lateralization was observed (z6-fold increase in lateral/transverse ratio, P<0.001). Optical mapping (figure) showed a significant decrease in the atrial conduction velocity (P<0.05, range from 15% to 25%), which was frequency-dependent (increased at faster rates). CONCLUSION: Long-term repetitive OSA leads to an AF substrate by remodeling Cx43 and inducing tissue fibrosis, which slow atrial conduction and produce an AF substrate.
151 PULMONARY VASCULAR & RIGHT VENTRICULAR INTERACTION IN LONG-STANDING ENDURANCE ATHLETES AT REST AND DURING EXERCISE T Gray, S Mak, S Wright, A Chelvanathan, S Esfandiari, F Fuchs, W Chan, Z Sasson, J Goodman Toronto, Ontario BACKGROUND: The pulmonary arterial circulation is a highlycompliant, low-pressure system that is functionally coupled to the right ventricle (RV). Chronic endurance athletes (EA) demonstrate RV enlargement proportional to that seen in the left ventricle. Limited, mostly non-invasive data suggests that EA have elevated pulmonary artery pressures (PAP) at rest and during acute exercise compared to untrained individuals. We sought to systematically characterize pulmonary artery-RV coupling at rest and during exercise in longstanding EA. METHODS: Healthy male subjects (n¼6; mean age 53.53.6 years) with >20 yrs. of endurance exercise training (mean VO2max ¼ 44.76.3) were recruited. Subjects underwent right-heart catheterization to determine pulmonary pressures (mmHg) and simultaneous echocardiography (ECHO), with measures obtained in a semi-upright position at rest and during cycle exercise at successive steady state heart rates of 100, 130 and 150 b/min. ECHO-derived cardiac output (Q) was determined from the left ventricular outflow tract cross sectional area and pulse Doppler velocity-time integral measurements. The mean pulmonary pressure (mPAP)-Q relation was assessed by linear regression and pulmonary vascular distensibility coefficient (a) was calculated, as was the pulmonary arterial elastance-RV end-systolic elastance ratio (Ea:Ees). RESULTS: Resting RV end-diastolic and end-systolic areas (22.32.4 and 12.41.7 cm2, respectively) were in the upper-range of reference values, as were basal, mid-cavity and
S147
highly-trained male athletes in order to characterize atrial function across a broader range of exercise intensities. We hypothesized that LA filling improves acutely during lightintensity exercise due to enhanced atrioventricular-plane displacement (AVPD) during LV systole, and that reduced diastolic filling time at moderate exercise intensities limits passive LA emptying and increases LA active emptying volume. METHODS: Ten healthy endurance-trained males (mean age ¼ 54 4 years) were studied at rest and during cycle-ergometry at light (w100 b/min, LE) and moderate (w130 b/min ME) intensity exercise. Doppler echocardiography was used to assess coupling and diastolic function. LA and LV volumes were measured using Simpson's method from 2D greyscale images in standard apical windows. AVPD was analyzed by tissue-tracking Doppler echocardiography. Simultaneous right heart catheterization was performed to measure hemodynamics, including pulmonary capillary wedge pressure (PCWP). RESULTS: Echocardiographic data was available from all subjects, with hemodynamic data available from 6 subjects; data is presented in Table 1. LV EDV increased from rest to LE and then to ME. During LV systole, AVPD increased from rest to LE, but did not increase further at ME. LA reservoir volume increased modestly from rest to LE, and remained constant. In contrast, during LV diastole, LA conduit volume increased during LE, and increased further at ME. LA active emptying volume increased from rest only at ME. PCWP increased acutely during LE, with partial normalization occurring during ME. CONCLUSION: AVPD, and thus the longitudinal component of LV systole, contributes to LA filling primarily during LE, but is a limited mechanism beyond LE. LA phasic function appears to shift from reliance on AVPD to an increase in conduit function and active emptying to maintain and increase LV EDV during ME. As LA reservoir volume remained stable from LE to ME, despite a decline in PCWP, this suggests possibly altered LA compliance during exercise.
149 DOES ATRIAL FIBRILLATION AFFECT OUTCOMES IN PATIENTS ADMITTED WITH ACUTE HEART FAILURE? INSIGHTS FROM THE ASCEND-HF TRIAL S Abualnaja, M Podder, AF Hernandez, JJ McMurray, PW Armstrong, JA Ezekowitz Edmonton, Alberta BACKROUND:
Acute heart failure (AHF) is a major cause of morbidity and mortality and commonly associated with atrial fibrillation (AF). Such patients are thought to be more symptomatic during admission, have higher heart rates at admission and discharge and poorer long term outcomes than patients in sinus rhythm. The basis for these assumptions are unsubstantiated. METHODS: AHF patients (n¼7007) enrolled in the ASCEND-HF trial were included. Details on heart rate (HR) and other clinical variables (including pre-existing or new onset AF) were collected on the case report form. Unadjusted and adjusted outcomes (using the ASCEND-HF multivariable model) are presented for 30-day and 180-days. RESULTS: There were 61.8% (n¼4330) patients in sinus rhythm and 38.2% (n¼2677) had AF. Patients with AF were older (72 vs. 63 years), more often smokers and had more comorbidities such as hypertension, and vascular disease. Patients with AHF and AF had a lower median BNP on admission than patients without AF (945 vs. 1040 pg/ml, p¼0.018) and higher median left ventricular ejection fraction (31% vs. 27%, p<0.001). Patients with vs. those without AF had similar ventricular rates on admission (81 vs. 83 bpm, p¼0.14) but were lower at discharge (74 vs. 78 bpm, p<0.001; Figure). Patients with AF did not differ with respect to the moderate or marked improvement in dyspnea at 6h or 24h (p 0.09). Patients with AF had higher unadjusted 30-day mortality/HF rehospitalization (11.6% vs. 8.6%, p<0.001) and 31 to 180-day mortality (11.1% vs. 8%, p<0.001) rates compared to patients without AF (Table). After adjustment, AF remained an independent predictor for worse clinical outcomes. CONCLUSION: Among patient admitted to the hospital with AHF, AF is associated with higher morbidity and mortality at 30-day and 180-day compared to those not in AF. AF remains an independent predictor, despite a well controlled ventricular rate.
Rest and exercise data Rest LV EDV (mL) AVPD (mm) LA Reservoir vol. (mL) LA Conduit vol. (mL)
117 ± 12 14 ± 1 33 ± 8 40 ± 8
Light Ex.
Moderate Ex. 129 ± 14
18 ± 2
**
17 ± 3‡
30 day all-cause mortality
41 ± 9
**
‡
126 ± 12
‡†
40 ± 8 *
‡†
46 ± 10
56 ±12
LA Active Empty. vol.(mL) 12 ± 4
16 ± 5
24 ± 9‡†
Mean PCWP (mmHg)
20 ± 2**
15 ± 5‡†
11 ± 3
Short and long-term outcomes Outcome N (%)
**
* p < 0.05, LE vs. Rest; ** p < 0.01, LE vs. Rest; ‡ p < 0.05, ME vs. Rest; † p < 0.05, ME vs. LE
All patients (N=7007)
HF without AF HF with AF Unadjusted Adjusted Odds* or (N=4330) (N=2677) p-value Hazard** ratio (95% CI)
267 (3.8)
143 (3.3)
124 (4.6)
0.005
1.20* (0.91 - 1.58)
30 day mortality or 666 (9.7) HF-rehosp
362 (8.6)
304 (11.6)
<0.001
1.20** (1.00 - 1.45)
31 to 180-day mortality
329 (8.0)
280 (11.1)
<0.001
1.16** (0.93 - 1.43)
609 (9.2)
*Odds Ratio, adjusted for ASCEND-HF 30-day all-cause-mortality model (age, blood urea nitrogen, serum sodium, baseline dyspnea, systolic blood pressure). **Hazard Ratio, adjusted for ASCEND-HF 30-day mortality/HF-readmission and 31 to 180-day mortality model (age, blood urea nitrogen, baseline sodium, creatinine and systolic blood pressure, history of cerebrovascular disease, depression, HF-hospitalization, qualifying episode of dyspnea and JVP).
S148
Canadian Journal of Cardiology Volume 29 2013
Johnson & Johnson 150 REPETITIVE OSA PROMOTES ATRIAL FIBRILLATION BY IMPAIRING ATRIAL CONDUCTION F Xiong, T Kato, Y Iwasaki, A Maguy, P Comtois, S Nattel Montréal, Québec BACKGROUND:
Patients with repetitive obstructive sleep apnea (OSA) have increased risks of developing atrial fibrillation (AF), but the mechanisms are poorly defined. In this work, we tested the hypothesis that long term repetitive OSA causes atrial structural remodeling and promotes AF by interfering with atrial conduction. METHODS: Twenty-week-old male rats were intubated and ventilated with air and 2% isoflurane. Repetitive OSA was mimicked by repetitive 2-min cycles (airway obstructed for 40 s/ 80 s recovery) 20 times daily, 5 days/week for 4 weeks. Non-OSA controls had the same procedure without obstruction. Fibrous tissue content and Cx43 expression were assessed by histomorphometry. Optical mapping (di-4ANEPPS) with blebbistatin for mechanical uncoupling was used to study impulse propagation. RESULTS: After 4 weeks of repeated OSA/nonOSA, AF was induced in 7 of 9 (78%) long term OSA rats vs 2 of 9 (22%) long term non-OSA rats (P<0.05). LA fibrous tissue content was greater in OSA (5.30.7% of cross sectional area) than non-OSA (3.70.5%, P<0.05). Cx43 expression was reduced by 55% in OSA and extensive lateralization was observed (z6-fold increase in lateral/transverse ratio, P<0.001). Optical mapping (figure) showed a significant decrease in the atrial conduction velocity (P<0.05, range from 15% to 25%), which was frequency-dependent (increased at faster rates). CONCLUSION: Long-term repetitive OSA leads to an AF substrate by remodeling Cx43 and inducing tissue fibrosis, which slow atrial conduction and produce an AF substrate.
151 PULMONARY VASCULAR & RIGHT VENTRICULAR INTERACTION IN LONG-STANDING ENDURANCE ATHLETES AT REST AND DURING EXERCISE T Gray, S Mak, S Wright, A Chelvanathan, S Esfandiari, F Fuchs, W Chan, Z Sasson, J Goodman Toronto, Ontario BACKGROUND: The pulmonary arterial circulation is a highlycompliant, low-pressure system that is functionally coupled to the right ventricle (RV). Chronic endurance athletes (EA) demonstrate RV enlargement proportional to that seen in the left ventricle. Limited, mostly non-invasive data suggests that EA have elevated pulmonary artery pressures (PAP) at rest and during acute exercise compared to untrained individuals. We sought to systematically characterize pulmonary artery-RV coupling at rest and during exercise in longstanding EA. METHODS: Healthy male subjects (n¼6; mean age 53.53.6 years) with >20 yrs. of endurance exercise training (mean VO2max ¼ 44.76.3) were recruited. Subjects underwent right-heart catheterization to determine pulmonary pressures (mmHg) and simultaneous echocardiography (ECHO), with measures obtained in a semi-upright position at rest and during cycle exercise at successive steady state heart rates of 100, 130 and 150 b/min. ECHO-derived cardiac output (Q) was determined from the left ventricular outflow tract cross sectional area and pulse Doppler velocity-time integral measurements. The mean pulmonary pressure (mPAP)-Q relation was assessed by linear regression and pulmonary vascular distensibility coefficient (a) was calculated, as was the pulmonary arterial elastance-RV end-systolic elastance ratio (Ea:Ees). RESULTS: Resting RV end-diastolic and end-systolic areas (22.32.4 and 12.41.7 cm2, respectively) were in the upper-range of reference values, as were basal, mid-cavity and