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Transesophageal echocardiography with tissue doppler imaging in the assessment of global and regional systolic and diastolic right ventricular function in atrial septal defects
The 7th Annual Scientific Meeting
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HFSA
S23
080
081
Systolic Dysfunction in Chronic Mitral Valve Regurgitation Joseph C. McGinley,1 Remus M. Berretta,1 Khuram Chaudry, 1Eric Rossman,1 John P. Gaughan,1 Kenneth B. Margulies1—1Cardiovascular Research, Temple University, Philadelphia, PA
Comparable Effects of Angiotensin Receptor 1 Antagonist vs ACE Inhibitor on Myocardial Fibrosis in Canine Heart Failure with Non-ACE Pathway Katsuya Onishi,1 Kaoru Dohi,2 Takafumi Koji,2 Kaoru Funabiki,2 Ryuji Okamoto,2 Masaki Tanabe,2 Takeshi Nakano2—1Department of Laboratory Medicine, Mie University School of Medicine, Tsu, Japan; 2The First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
Background: The purpose of this study was to determine the in-vivo rate dependent alterations in systolic functional reserve in a canine model of chronic mitral valve regurgitation (MR) and investigate whether the changes are due to altered hemodynamic loads or intrinsic cardiac dysfunction in trabecular and cellular studies. Methods: A pressure-tipped catheter was inserted into the left ventricle (LV) of eight dogs (20–22 kg) and positive dP/dt measured at several pacing rates. Mild MR was produced through a fixed structural lesion to the mitral valve apparatus. Incremental ramped pacing induced LV dilation over an eight-month period. The pacer was deactivated and the dogs followed for an additional six weeks. Prior to explant, positive dP/dt was measured at several pacing rates. The heart was arrested, explanted and developed force and fractional shortening measured in isolated isometric LV trabeculae and unloaded myocytes at several stimulation rates. Similar studies were performed in six control dogs. Results: Following the ten-month experimental period, there was a significant decrease in positive dP/dt at each pacing rate compared to baseline studies (p ⬍ 0.01) and an attenuated frequency relationship with chronic MR. Isolated trabecular studies demonstrated a significantly lower developed force at increased stimulation rates in the chronic MR group compared to controls (p ⬍ 0.05) and a negative force-frequency relation. Isolated myocytes possessed a negative shortening-frequency relationship in both groups with a more pronounced decline and significantly lower fractional shortening values with chronic MR (p ⬍ 0.001). Conclusions: Chronic MR resulted in a significant reduction in in-vivo systolic function with an impaired reserve capacity. Isometric trabecular and unloaded myocyte studies also demonstrated rate dependent impairment in systolic function with a reduced function reserve capacity. The results of this study indicate the reduced contractile function observed in chronic MR is due to primary alterations at the cellular and tissue level.
ACE inhibitor (ACEI) and/or angiotensin II (AII) receptor antagonist (ATRA) prevent myocardial fibrosis mainly through the inhibition of AII. ATRA inhibits effects of AII to the greater extent than ACEI, while it has been suggested that kinins increased by ACEI directly prevents myocardial fibrosis. Accordingly, this study was designed to investigate whether ATRA, candesartan prevented myocardial fibrosis more effectively than ACEI, enarapril in animals with non-ACE pathway. Methods and Results: The study was performed in 18 canine pacing-induced CHF, which has non-ACE pathway. Beginning 7 days after rapid ventricular pacing (240 bpm), animals were treated with 1 of 3 treatment regimens: no therapy (n ⫽ 6), candesartan (1.5 mg/kg/ day, n ⫽ 6), and enarapril (1.9 mg/kg/day, n ⫽ 6). Three weeks after these treatments, values of collagen volume fraction of the left ventricle (LV) in candesartan group were significantly lower than no therapy and enarapril groups (p ⬍ 0.05). The collagen I & III mRNA was significantly downregulated in candesartan group to compare with no therapy and enarapril groups. However, there were no significant differences in LV chamber stiffness, which was determined by LV pressure-volume relation obtained by a conductance catheter with a micromanometer among 3 groups. Conclusions: These findings suggest that candesartan can prevent myocardial fibrosis to the greater extent than enarapril in canine heart failure with non-ACE pathway. However, LV chamber stiffness is not a sensitive parameter to reflect the myocardial fibrosis.
082
083
Transesophageal Echocardiography with Tissue Doppler Imaging in the Assessment of Global and Regional Systolic and Diastolic Right Ventricular Function in Atrial Septal Defects Antonio Vitarelli,1 Ysabel Conde,1 Ester Cimmino,1 Tiziana Leone,1 Simona D’Orazio,1 Riccardo Colantonio,1 Ilaria D’Angeli,1 Simona Stellato1—1Cardiac Dept., La Sapienza University, Rome, Italy
Utility of Heart Rate Recovery as a Predictor for Maximum Oxygen Consumption in Patients with Chronic Heart Failure (CHF) Svetlana L. Barbarash,1 Allison Arwady,1 Rochelle L. Goldsmith,1 Timothy J. Vittorio,1 Katarzyna Hryniewicz,2 Joyce L. Burcham,1 Stuart D. Katz,2 Ulrich P. Jorde1—1Medicine, Columbia-Presbyterian Medical Center, New York, NY, USA; 2 Medicine, Yale University School of Medicine, New Haven, CT
Background: Evaluation of global and regional right ventricular (RV) systolic and diastolic function in atrial septal defects (ASD) is still a challenging post-surgical clinical problem, especially in adult patients (pts) We investigated whether high frame rate tissue Doppler imaging (TDI, Toshiba corp.) may provide quantitative assessment of RV function in ASD pts. Methods: Twenty-three pts with ostium secundum ASD, aged 25 ⫾ 9 years, were studied with transesophageal echocardiography. Twelve pts underwent corrective surgery. 11 subjects with no signs of heart disease were used as a control group. ASD pts were classified in 3 groups according to 2D/color Doppler defect and shunt size (group “1” large, group “2” medium, group “3” small). Peak mean systolic (Sw) and diastolic (Ew, Aw) wall velocities were acquired from the 4chamber view in the myocardia [septum (IVS) and free wall (FW)]. TDI wall velocities during systole (Sa), early relaxation (Ea) and atrial systole (Aa) were also measured in the tricuspid annulus. Satisfactory TDI data could be obtained in all pts at end expiration, independent of quality of RV wall motion. Results: Compared to controls, group “1” pts had lower mean FW velocities (Sw ⫽ 5.5 ⫾ 1.9 vs 8.3 ⫾ 2.1 cm/ s –p ⬍ 0.005–; Ew ⫽ 5.8 ⫾ 1.9 vs 9.4 ⫾ 2.2 cm/s –p ⬍ 0.001–; Aw ⫽ 3.5 ⫾ 1.4 vs 3.6 ⫾ 1.8 cm/s –p ⫽ NS–) and lower annulus velocities both in systole and diastole (Sa ⫽ 5.3 ⫾ 1.3 vs 8.9 ⫾ 1.3 cm/s –p ⬍ 0.001–; Ea ⫽ 6.2 ⫾ 2.4 vs 13.3 ⫾ 2.4 cm/s – p ⬍ 0.001–; Aa ⫽ 7.8 ⫾ 2.2 vs 7.1 ⫾ 2.3 cm/s –p ⫽ NS–). Also, group “1” pts had lower mean FW Sw and Ew velocities compared to IVS wall velocities (p ⬍ 0.005). Group “2” pts had preserved systolic velocities but decreased regional and annular early diastolic velocities suggesting impaired relaxation (Ea/Aa 0.87 ⫾ 0.28 vs 1.64 ⫾ 0.31 –p ⬍ 0.0001–). Group “3” pts had preserved systolic and diastolic velocities. Conclusion: Thus, TDI is useful in evaluating systolic and diastolic RV abnormalities, could corroborate the need of surgery in pts with volume overload, and may aid in monitoring RV function during post-surgical followup.
Background: Heart rate recovery after maximal exercise is highly correlated (r ⬎ 0.8) with peak oxygen consumption (VO2) in healthy individuals and has recently been proposed to be an independent predictor of mortality in patients with CHF. Peak VO2 is one of the strongest predictors of survival in patients with CHF. In contrast to peak VO2 measurement, which requires analysis of expired gases, heart rate recovery after exercise is easily obtained. Accordingly, the current study was undertaken to determine the association between VO2 and heart rate recovery in patients with CHF. Methods: Retrospective data on VO2 and heart rate recovery were analyzed in 348 patients with CHF secondary to left ventricular systolic dysfunction (LVEF ⬍ 40%) on optimal medical therapy who had undergone standardized treadmill cardiopulmonary exercise tolerance testing (CPETT). Patients exercised on a treadmill using a graded work rate protocol with work rate gradually increasing to a symptom-limited maximum. Expired gases were analyzed throughout exercise for determination of peak oxygen uptake. Peak VO2 was defined as the highest value of oxygen uptake attained in the final 20 seconds of exercise, when the respiratory exchange ratio was greater than 1.0. Heart rate and blood pressure were monitored throughout exercise and recovery. Heart rate recovery was calculated for each patient as maximum achieved heart rate minus heart rate at one minute after exercise. Results: Baseline clinical characteristics were as follows: [Age 51 ⫾ 10 yrs, LVEF 27 ⫾ 9%, 75% of patients were male, 25% were female, etiology of CHF was 40% ischemic and 60% nonischemic]. Heart rate recovery and peak VO2 were correlated (r ⫽ 0.47, P ⬍ 0.05) and this degree of correlation was similar in patients receiving beta-blockers (r ⫽ 0.48, P ⬍ 0.05) as well as in those patients not receiving beta-blockers (r ⫽ 0.44, P ⬍ 0.05). Conclusion: Heart rate recovery is only moderately correlated with peak VO2 in patients with CHF regardless of concomitant beta-blocker use. This modest correlation of two strong independent predictors of outcome might prove useful when combining them in multivariate outcome scores for patients with CHF.
•
HFSA
S23
080
081
Systolic Dysfunction in Chronic Mitral Valve Regurgitation Joseph C. McGinley,1 Remus M. Berretta,1 Khuram Chaudry, 1Eric Rossman,1 John P. Gaughan,1 Kenneth B. Margulies1—1Cardiovascular Research, Temple University, Philadelphia, PA
Comparable Effects of Angiotensin Receptor 1 Antagonist vs ACE Inhibitor on Myocardial Fibrosis in Canine Heart Failure with Non-ACE Pathway Katsuya Onishi,1 Kaoru Dohi,2 Takafumi Koji,2 Kaoru Funabiki,2 Ryuji Okamoto,2 Masaki Tanabe,2 Takeshi Nakano2—1Department of Laboratory Medicine, Mie University School of Medicine, Tsu, Japan; 2The First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
Background: The purpose of this study was to determine the in-vivo rate dependent alterations in systolic functional reserve in a canine model of chronic mitral valve regurgitation (MR) and investigate whether the changes are due to altered hemodynamic loads or intrinsic cardiac dysfunction in trabecular and cellular studies. Methods: A pressure-tipped catheter was inserted into the left ventricle (LV) of eight dogs (20–22 kg) and positive dP/dt measured at several pacing rates. Mild MR was produced through a fixed structural lesion to the mitral valve apparatus. Incremental ramped pacing induced LV dilation over an eight-month period. The pacer was deactivated and the dogs followed for an additional six weeks. Prior to explant, positive dP/dt was measured at several pacing rates. The heart was arrested, explanted and developed force and fractional shortening measured in isolated isometric LV trabeculae and unloaded myocytes at several stimulation rates. Similar studies were performed in six control dogs. Results: Following the ten-month experimental period, there was a significant decrease in positive dP/dt at each pacing rate compared to baseline studies (p ⬍ 0.01) and an attenuated frequency relationship with chronic MR. Isolated trabecular studies demonstrated a significantly lower developed force at increased stimulation rates in the chronic MR group compared to controls (p ⬍ 0.05) and a negative force-frequency relation. Isolated myocytes possessed a negative shortening-frequency relationship in both groups with a more pronounced decline and significantly lower fractional shortening values with chronic MR (p ⬍ 0.001). Conclusions: Chronic MR resulted in a significant reduction in in-vivo systolic function with an impaired reserve capacity. Isometric trabecular and unloaded myocyte studies also demonstrated rate dependent impairment in systolic function with a reduced function reserve capacity. The results of this study indicate the reduced contractile function observed in chronic MR is due to primary alterations at the cellular and tissue level.
ACE inhibitor (ACEI) and/or angiotensin II (AII) receptor antagonist (ATRA) prevent myocardial fibrosis mainly through the inhibition of AII. ATRA inhibits effects of AII to the greater extent than ACEI, while it has been suggested that kinins increased by ACEI directly prevents myocardial fibrosis. Accordingly, this study was designed to investigate whether ATRA, candesartan prevented myocardial fibrosis more effectively than ACEI, enarapril in animals with non-ACE pathway. Methods and Results: The study was performed in 18 canine pacing-induced CHF, which has non-ACE pathway. Beginning 7 days after rapid ventricular pacing (240 bpm), animals were treated with 1 of 3 treatment regimens: no therapy (n ⫽ 6), candesartan (1.5 mg/kg/ day, n ⫽ 6), and enarapril (1.9 mg/kg/day, n ⫽ 6). Three weeks after these treatments, values of collagen volume fraction of the left ventricle (LV) in candesartan group were significantly lower than no therapy and enarapril groups (p ⬍ 0.05). The collagen I & III mRNA was significantly downregulated in candesartan group to compare with no therapy and enarapril groups. However, there were no significant differences in LV chamber stiffness, which was determined by LV pressure-volume relation obtained by a conductance catheter with a micromanometer among 3 groups. Conclusions: These findings suggest that candesartan can prevent myocardial fibrosis to the greater extent than enarapril in canine heart failure with non-ACE pathway. However, LV chamber stiffness is not a sensitive parameter to reflect the myocardial fibrosis.
082
083
Transesophageal Echocardiography with Tissue Doppler Imaging in the Assessment of Global and Regional Systolic and Diastolic Right Ventricular Function in Atrial Septal Defects Antonio Vitarelli,1 Ysabel Conde,1 Ester Cimmino,1 Tiziana Leone,1 Simona D’Orazio,1 Riccardo Colantonio,1 Ilaria D’Angeli,1 Simona Stellato1—1Cardiac Dept., La Sapienza University, Rome, Italy
Utility of Heart Rate Recovery as a Predictor for Maximum Oxygen Consumption in Patients with Chronic Heart Failure (CHF) Svetlana L. Barbarash,1 Allison Arwady,1 Rochelle L. Goldsmith,1 Timothy J. Vittorio,1 Katarzyna Hryniewicz,2 Joyce L. Burcham,1 Stuart D. Katz,2 Ulrich P. Jorde1—1Medicine, Columbia-Presbyterian Medical Center, New York, NY, USA; 2 Medicine, Yale University School of Medicine, New Haven, CT
Background: Evaluation of global and regional right ventricular (RV) systolic and diastolic function in atrial septal defects (ASD) is still a challenging post-surgical clinical problem, especially in adult patients (pts) We investigated whether high frame rate tissue Doppler imaging (TDI, Toshiba corp.) may provide quantitative assessment of RV function in ASD pts. Methods: Twenty-three pts with ostium secundum ASD, aged 25 ⫾ 9 years, were studied with transesophageal echocardiography. Twelve pts underwent corrective surgery. 11 subjects with no signs of heart disease were used as a control group. ASD pts were classified in 3 groups according to 2D/color Doppler defect and shunt size (group “1” large, group “2” medium, group “3” small). Peak mean systolic (Sw) and diastolic (Ew, Aw) wall velocities were acquired from the 4chamber view in the myocardia [septum (IVS) and free wall (FW)]. TDI wall velocities during systole (Sa), early relaxation (Ea) and atrial systole (Aa) were also measured in the tricuspid annulus. Satisfactory TDI data could be obtained in all pts at end expiration, independent of quality of RV wall motion. Results: Compared to controls, group “1” pts had lower mean FW velocities (Sw ⫽ 5.5 ⫾ 1.9 vs 8.3 ⫾ 2.1 cm/ s –p ⬍ 0.005–; Ew ⫽ 5.8 ⫾ 1.9 vs 9.4 ⫾ 2.2 cm/s –p ⬍ 0.001–; Aw ⫽ 3.5 ⫾ 1.4 vs 3.6 ⫾ 1.8 cm/s –p ⫽ NS–) and lower annulus velocities both in systole and diastole (Sa ⫽ 5.3 ⫾ 1.3 vs 8.9 ⫾ 1.3 cm/s –p ⬍ 0.001–; Ea ⫽ 6.2 ⫾ 2.4 vs 13.3 ⫾ 2.4 cm/s – p ⬍ 0.001–; Aa ⫽ 7.8 ⫾ 2.2 vs 7.1 ⫾ 2.3 cm/s –p ⫽ NS–). Also, group “1” pts had lower mean FW Sw and Ew velocities compared to IVS wall velocities (p ⬍ 0.005). Group “2” pts had preserved systolic velocities but decreased regional and annular early diastolic velocities suggesting impaired relaxation (Ea/Aa 0.87 ⫾ 0.28 vs 1.64 ⫾ 0.31 –p ⬍ 0.0001–). Group “3” pts had preserved systolic and diastolic velocities. Conclusion: Thus, TDI is useful in evaluating systolic and diastolic RV abnormalities, could corroborate the need of surgery in pts with volume overload, and may aid in monitoring RV function during post-surgical followup.
Background: Heart rate recovery after maximal exercise is highly correlated (r ⬎ 0.8) with peak oxygen consumption (VO2) in healthy individuals and has recently been proposed to be an independent predictor of mortality in patients with CHF. Peak VO2 is one of the strongest predictors of survival in patients with CHF. In contrast to peak VO2 measurement, which requires analysis of expired gases, heart rate recovery after exercise is easily obtained. Accordingly, the current study was undertaken to determine the association between VO2 and heart rate recovery in patients with CHF. Methods: Retrospective data on VO2 and heart rate recovery were analyzed in 348 patients with CHF secondary to left ventricular systolic dysfunction (LVEF ⬍ 40%) on optimal medical therapy who had undergone standardized treadmill cardiopulmonary exercise tolerance testing (CPETT). Patients exercised on a treadmill using a graded work rate protocol with work rate gradually increasing to a symptom-limited maximum. Expired gases were analyzed throughout exercise for determination of peak oxygen uptake. Peak VO2 was defined as the highest value of oxygen uptake attained in the final 20 seconds of exercise, when the respiratory exchange ratio was greater than 1.0. Heart rate and blood pressure were monitored throughout exercise and recovery. Heart rate recovery was calculated for each patient as maximum achieved heart rate minus heart rate at one minute after exercise. Results: Baseline clinical characteristics were as follows: [Age 51 ⫾ 10 yrs, LVEF 27 ⫾ 9%, 75% of patients were male, 25% were female, etiology of CHF was 40% ischemic and 60% nonischemic]. Heart rate recovery and peak VO2 were correlated (r ⫽ 0.47, P ⬍ 0.05) and this degree of correlation was similar in patients receiving beta-blockers (r ⫽ 0.48, P ⬍ 0.05) as well as in those patients not receiving beta-blockers (r ⫽ 0.44, P ⬍ 0.05). Conclusion: Heart rate recovery is only moderately correlated with peak VO2 in patients with CHF regardless of concomitant beta-blocker use. This modest correlation of two strong independent predictors of outcome might prove useful when combining them in multivariate outcome scores for patients with CHF.