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B204 Left ventricular diastolic dyssynchrony contributes to abnormal diastolic filling in ischemic diastolic heart failure
S44
Oral Sessions / International Journal of Cardiology 125 Suppl. 1 (2008) S39–S50
decreased much lower than that of IP+IR group (2.13±0.56 vs 2.89±0.47, P < 0.05). Conclusion: The protection effect of ischemic preconditioning on ischemic/reperfusion myocardium and coronary flow reserve can be objectively evaluated by MCE and CFDI. B204 Left ventricular diastolic dyssynchrony contributes to abnormal diastolic filling in ischemic diastolic heart failure P.W. Lee *, Q. Zhang, C.P. Chan, G. Yip, C.M. Yu. Division of Cardiology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China Background: Ischemic heart disease (IHD) is a recognized cause of diastolic heart failure (DHF) but the pathophysiologic mechanisms are not completely understood. This study hypothesized that left ventricular diastolic dyssynchrony contributes to diastolic dysfunction and ischemic DHF. Method: Fifty-four patients with ischemic DHF, 40 patients with IHD but no heart failure symptoms, and 97 age- and sex-matched healthy subjects were studied with tissue Doppler echocardiography. Left ventricular diastolic and systolic dyssynchrony were determined by the standard deviation of the time to peak early diastolic (TeSD) and systolic (Ts-SD) myocardial velocities, respectively, in a 12-segment model. Left ventricular diastolic filling was classified as normal, impaired relaxation (grade 1), pseudo-normal filling (grade 2), and restrictive filling (grade 3) by Doppler echocardiography. Results: Patients with DHF had significantly greater degree of left ventricular diastolic dyssynchrony but similar degree of systolic dyssynchrony, ejection fraction, and longitudinal systolic function compared to patients with no heart failure symptoms (Table 1). Left ventricular diastolic dyssynchrony increased progressively with increasing severity of diastolic dysfunction (Figure 1). Conclusions: Left ventricular diastolic dyssynchrony is associated with abnormal diastolic function in patients with IHD. Most severe diastolic dyssynchrony was observed in patients with pseudo-normal and restrictive filling suggestive of elevated ventricular filling pressure and may contribute to the development of ischemic DHF. Table 1. Clinical and echocardiographic characteristics IHD
Age, yr Male gender NYHA class* I II III IV QRS duration, ms Ejection fraction, % Te-SD, ms* Ts-SD, ms Em, cm/s† Sm, cm/s
DHF (n = 54)
No DHF (n = 40)
Controls (n = 97)
65±10 37 (74)
61±10 34 (77)
61±13 73 (75)
0 (0) 19 (58) 16 (32) 5 (10) 84.0±15.7 69±11‡ 33.2±13.1‡ 34.1±16.6‡ 4.7±1.7‡ 5.1±1.1‡
44 (100) 0 (0) 0 (0) 0 (0) 82.1±14.2 69±11‡ 17.1±1.5 29.7±18.1‡ 6.0±1.9‡ 5.1±1.5‡
... ... ... ... ... 79±6 19.3±7.2 17.4±8.2 7.5±1.6 6.4±1.1
Data are represented as mean±SD or number of patients (%). Ellipses indicate not applicable. DHF, diastolic heart failure; Em, mean basal myocardial early diastolic velocity; IHD, ischemic heart disease; NYHA, New York Heart Association; Sm, mean basal myocardial systolic velocity; Te-SD, diastolic dyssynchrony index; Ts-SD, systolic dyssynchrony index. *P < 0.001 between DHF patients and IHD patients with no DHF. † P = 0.003 between DHF patients and IHD patients with no DHF. ‡ P < 0.001 compared to controls.
Figure 1. Scatter plots of Te-SD in IHD patients. Blue and red plots represented IHD patients with DHF and without DHF, respectively. Grade 0 = normal diastolic function; grade 1 = impaired relaxation; grade 2 = pseudo-normal filling; grade 3 = restrictive filling. *P = 0.002 compared to normal; † P = 0.03 compared to grade 1. ‡ P < 0.001 compared to normal, grade 1 and grade 2.
B205 Cardiac ryanodine receptor mutation leads to accelerated development of heart failure X.H. Wehrens *. Department of Molecular Physiology, Baylor College of Medicine, Houston, TX, USA Objectives of the study: Mutations in the gene encoding the cardiac ryanodine receptor (RyR2) – the calcium release channel required for excitation–contraction coupling in the heart – have been linked to an increased propensity towards heart failure in patients. These gain-of-function defects have been postulated to increase sarcoplasmic reticulum calcium leakage, leading to reduced cardiac contractility. Here, we tested the hypothesis that mutation R176Q in RyR2 in genetargeted mice leads to accelerated development of cardiac dysfunction following pressure-overload. Methods: R176Q/+ heterozygous (n = 11) and wildtype (WT; n = 12) mice were subjected to transverse aortic constriction (TAC), which causes pressure-overload. Cardiac function was evaluated using echocardiography before, and 4 and 8 weeks after TAC. Following pressure-volume loop measurements at 8 weeks post-TAC, mice were sacrificed and routine myocardial histology was performed. Results: Compared with WT mice, R176Q/+ mutant mice displayed more pronounced cardiac remodeling induced by chronic stress. Ejection fraction and fractional shortening were significantly lower in R176Q/+ mice compared with WT at 4 and 8 weeks post-TAC. Cardiac dimensions including end-diastolic diameter were larger in R176Q/+ (4.1±0.1) than WT (3.9±0.1) mice at 8 weeks post-TAC. Heart weight-to-body weight ratios were 11.3±0.6 for R176Q/+ and 7.7±0.3 for WT mice (P < 0.05). Conclusions: Taken together, our results reveal that a genetic mutation in RyR2 accelerates the development of heart failure induced by pressure-overload. Therefore, inherited or acquired functional defects in intracellular calcium release channel function may adversely influence the pathogenesis of heart failure.
Oral Sessions / International Journal of Cardiology 125 Suppl. 1 (2008) S39–S50
decreased much lower than that of IP+IR group (2.13±0.56 vs 2.89±0.47, P < 0.05). Conclusion: The protection effect of ischemic preconditioning on ischemic/reperfusion myocardium and coronary flow reserve can be objectively evaluated by MCE and CFDI. B204 Left ventricular diastolic dyssynchrony contributes to abnormal diastolic filling in ischemic diastolic heart failure P.W. Lee *, Q. Zhang, C.P. Chan, G. Yip, C.M. Yu. Division of Cardiology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China Background: Ischemic heart disease (IHD) is a recognized cause of diastolic heart failure (DHF) but the pathophysiologic mechanisms are not completely understood. This study hypothesized that left ventricular diastolic dyssynchrony contributes to diastolic dysfunction and ischemic DHF. Method: Fifty-four patients with ischemic DHF, 40 patients with IHD but no heart failure symptoms, and 97 age- and sex-matched healthy subjects were studied with tissue Doppler echocardiography. Left ventricular diastolic and systolic dyssynchrony were determined by the standard deviation of the time to peak early diastolic (TeSD) and systolic (Ts-SD) myocardial velocities, respectively, in a 12-segment model. Left ventricular diastolic filling was classified as normal, impaired relaxation (grade 1), pseudo-normal filling (grade 2), and restrictive filling (grade 3) by Doppler echocardiography. Results: Patients with DHF had significantly greater degree of left ventricular diastolic dyssynchrony but similar degree of systolic dyssynchrony, ejection fraction, and longitudinal systolic function compared to patients with no heart failure symptoms (Table 1). Left ventricular diastolic dyssynchrony increased progressively with increasing severity of diastolic dysfunction (Figure 1). Conclusions: Left ventricular diastolic dyssynchrony is associated with abnormal diastolic function in patients with IHD. Most severe diastolic dyssynchrony was observed in patients with pseudo-normal and restrictive filling suggestive of elevated ventricular filling pressure and may contribute to the development of ischemic DHF. Table 1. Clinical and echocardiographic characteristics IHD
Age, yr Male gender NYHA class* I II III IV QRS duration, ms Ejection fraction, % Te-SD, ms* Ts-SD, ms Em, cm/s† Sm, cm/s
DHF (n = 54)
No DHF (n = 40)
Controls (n = 97)
65±10 37 (74)
61±10 34 (77)
61±13 73 (75)
0 (0) 19 (58) 16 (32) 5 (10) 84.0±15.7 69±11‡ 33.2±13.1‡ 34.1±16.6‡ 4.7±1.7‡ 5.1±1.1‡
44 (100) 0 (0) 0 (0) 0 (0) 82.1±14.2 69±11‡ 17.1±1.5 29.7±18.1‡ 6.0±1.9‡ 5.1±1.5‡
... ... ... ... ... 79±6 19.3±7.2 17.4±8.2 7.5±1.6 6.4±1.1
Data are represented as mean±SD or number of patients (%). Ellipses indicate not applicable. DHF, diastolic heart failure; Em, mean basal myocardial early diastolic velocity; IHD, ischemic heart disease; NYHA, New York Heart Association; Sm, mean basal myocardial systolic velocity; Te-SD, diastolic dyssynchrony index; Ts-SD, systolic dyssynchrony index. *P < 0.001 between DHF patients and IHD patients with no DHF. † P = 0.003 between DHF patients and IHD patients with no DHF. ‡ P < 0.001 compared to controls.
Figure 1. Scatter plots of Te-SD in IHD patients. Blue and red plots represented IHD patients with DHF and without DHF, respectively. Grade 0 = normal diastolic function; grade 1 = impaired relaxation; grade 2 = pseudo-normal filling; grade 3 = restrictive filling. *P = 0.002 compared to normal; † P = 0.03 compared to grade 1. ‡ P < 0.001 compared to normal, grade 1 and grade 2.
B205 Cardiac ryanodine receptor mutation leads to accelerated development of heart failure X.H. Wehrens *. Department of Molecular Physiology, Baylor College of Medicine, Houston, TX, USA Objectives of the study: Mutations in the gene encoding the cardiac ryanodine receptor (RyR2) – the calcium release channel required for excitation–contraction coupling in the heart – have been linked to an increased propensity towards heart failure in patients. These gain-of-function defects have been postulated to increase sarcoplasmic reticulum calcium leakage, leading to reduced cardiac contractility. Here, we tested the hypothesis that mutation R176Q in RyR2 in genetargeted mice leads to accelerated development of cardiac dysfunction following pressure-overload. Methods: R176Q/+ heterozygous (n = 11) and wildtype (WT; n = 12) mice were subjected to transverse aortic constriction (TAC), which causes pressure-overload. Cardiac function was evaluated using echocardiography before, and 4 and 8 weeks after TAC. Following pressure-volume loop measurements at 8 weeks post-TAC, mice were sacrificed and routine myocardial histology was performed. Results: Compared with WT mice, R176Q/+ mutant mice displayed more pronounced cardiac remodeling induced by chronic stress. Ejection fraction and fractional shortening were significantly lower in R176Q/+ mice compared with WT at 4 and 8 weeks post-TAC. Cardiac dimensions including end-diastolic diameter were larger in R176Q/+ (4.1±0.1) than WT (3.9±0.1) mice at 8 weeks post-TAC. Heart weight-to-body weight ratios were 11.3±0.6 for R176Q/+ and 7.7±0.3 for WT mice (P < 0.05). Conclusions: Taken together, our results reveal that a genetic mutation in RyR2 accelerates the development of heart failure induced by pressure-overload. Therefore, inherited or acquired functional defects in intracellular calcium release channel function may adversely influence the pathogenesis of heart failure.