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Indices of Right Ventricular Contractility in a Model of Chronic Pulmonary Hypertension
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The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2013
Methods and Materials: All consecutive Tx candidates with PAH (except PAH due to congenital shunts) without RVF at their first evaluation (2006-2010) were included in the study. At selection, after exercise testing and NT-proBNP measurement, patients underwent echocardiography with tissue Doppler and strain imaging. Examinations were repeated at each follow-up. Collected data were tested for ability to predict time course of RV function and Tx-free patient survival. Results: Of 64 studied patients, 22 developed RVF. The 5-year Tx-free survival with and without RV worsening was 89% and 30%, respectively (po0.001). Comparing the initial data from patients with and without subsequent RV worsening we found no differences in RV size, RVEF, pulmonary arterial pressure, right atrial size or tricuspid annulus systolic excursion. However, those with subsequent RV worsening had initially higher NT-proBNP and lower RV DP/Dt, and strain analysis revealed higher RV systolic dyssynchrony, lower systolic afterload-corrected strain rate and higher diastolic early/late strain rate (SrE/SrA) ratio (po0.01). At certain cut-off values, DP/Dt and SrE/SrA showed the highest predictive values for Z2 year freedom from RVF (86.7 and 84.8%, respectively) and Tx-free survival (84.2 and 83.8%, respectively). Conclusions: In PAH patients referred for Tx, RV DP/Dt and certain strain parameters can predict the time course of RV function and Txfree survival. Our results suggest that these parameters can improve Tx listing decisions. 192 Indices of Right Ventricular Contractility in a Model of Chronic Pulmonary Hypertension J. Guihaire,1 F. Haddad,1 O. Mercier,1 D. Boulate,1 B. Decante,1 P. Herve,1 P. Dartevelle,1 M. Humbert,2 E. Fadel.1 1Laboratory of Surgical Research, Inserm U999, Marie Lannelongue Hospital, University of South Paris, Le Plessis Robinson, France; 2Service de ˆ ˆ Pneumologie, Inserm U999, Hopital Bicetre, University of South Paris, ˆ Le Kremlin-Bicetre, France. Purpose: Acceleration of the myocardium during isovolumic contraction (IVA) and right ventricular myocardial performance index (RVMPI) have been previously described as indices of right ventricular (RV) contractility. However they have not been validated in a model of chronic pressure overload. Methods and Materials: Chronic pulmonary hypertension (PH) was induced in pigs by ligation of the left pulmonary artery (PA) followed by weekly embolizations of the right lower lobe for 5 weeks (PH group, n¼11). Sham-operated animals were used as controls (n¼5). RV remodeling was assessed using echocardiography, conductance catheterism and stroke volume (SV) reserve following dobutamine infusion (5 mcg/kg/min). Right ventricular fractional area change (RVFAC),
tricuspid annular plane systolic excursion (TAPSE), RVMPI and IVA were used for RV systolic function assessment. Results: At 5 weeks, mean PA pressure (35⫾9 vs. 13⫾2 mm Hg, Po0.01) and PA elastance (0.90⫾0.44 vs. 0.29⫾0.06 mm Hg/ml, P¼0.01) were increased in PH animals compared to controls. Although RV elastance increased at 5 weeks in the PH group (0.55⫾0.14 vs. 0.34⫾0.06 mm Hg/ml, P¼0.007), RV-PA coupling measured by the ratio of RV to PA elastance was decreased at 5 weeks (0.68⫾0.17 vs. 1.18⫾0.18, Po0.001). RVAC, TAPSE, RVMPI and IVA were positively correlated with RV-PA coupling but not with RV elastance (R2¼0.84, Po0.001; R2¼0.62, P¼0.017; R2¼0.59, P¼0.003; R2¼0.83, Po0.001). IVA correlated with SV reserve (R2 ¼0.71, Po0.001). On multivariate analysis, IVA was independently associated with RV-PA coupling (R2¼0.83, Po0.001). Conclusions: IVA as well as RVMPI, RVFAC and TAPSE are markers of RV-PA coupling rather than RV contractility in a model of chronic PH. 193 Role of Angiogenesis in the Right Ventricle Remodeling in Response to Pulmonary Hypertension P.E. Noly,1,2 F. Haddad,1,2 O. Mercier,1,2 P. Dorfmuller,1,2 B. Decante,1,2 P. Dartevelle,1,2 E. Fadel.1,2 1Surgical Research Lab, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; 2 INSERM U999, Le Plessis Robinson, France. Purpose: Right ventricular (RV) remodeling consisting of RV hypertrophy and increase in contractility occurs in response to pulmonary hypertension (PH) In congenital heart disease (CHD), the right ventricle remains compensated longer than in other types of PH. We hypothesized that better matched myocardial angiogenesis contributes to delay the transition to RV failure in CHD. Methods and Materials: We induced chronic PH over a 20 weeks period in a Shunt group (n¼5) by creating an aorto to pulmonary shunt and in an chronic thromboembolic PH (CTEPH group, n¼5) by ligating the left pulmonary artery (PA) followed by weekly embolizations of the right lower lobe for weekly. In the Sham group (n¼5), the pigs were studied 20 weeks after a left PA dissection. We assessed hemodynamics using right heart catherterization and RV structural and functional remodeling using echocardiography and pressure-volume loops measurement. Myocaridal angiogenesis of the RV was studied by measuring capillary density. Results: At 20 weeks, mean PA pressure (26.8 ⫾ 1.4 mm Hg vs 22.8 ⫾0.9 mm Hg, p¼NS) and RV stroke work (SW) (2192⫾ 255 mmHg/ml vs 2110 ⫾211 mmHg/ml, p¼NS) were not significantly different in the CTEPH and Shunt groups but significantly more elevated when compared to the Sham group (14.8 ⫾ 0.8 mm Hg and 1124⫾44 mmHg/ml, respectively; po0.01). Although RV wall thickness was similarly increased in both PH groups when compared to Sham (po0.001), TAPSE and RVFAC values were only decreased in CTEPH animals (po0.05). Similarly, the RV elastance was significantly increased ( p o0,05) and the ventriculo-arterial coupling was decreased ( po 0,05) only in the CTEPH group. Although the cardiomyocyte diameter was similarly increased in both P groups (po0.05), the capillary density was only increased in the Shunt group (po0.05). Conclusions: In PH induced by systemic to pulmonary shunt, the transition from RV compensated hypertrophy to RV failure is delayed compared to similar PH in a CTEPH model. Myocardial capillary density appears to be preserved in the right ventricle of shunt models. 194 Right Ventricular Support for Pulmonary Arterial Hypertension: An Acute Feasibility Study in Sheep T. Verbelen,1 J. Verhoeven,1 M. Ghoda,1 I. Van Tichelen,1 M. Delcroix,2 F. Rega,1 B. Meyns.1 1Experimental Cardiac Surgery, KULeuven, Leuven, Belgium; 2Pneumology, University Hospitals Leuven, Leuven, Belgium. Purpose: Mechanical support of the failing right ventricle (RV) can be a life-saving option in patients with pulmonary hypertension. Since the
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2013
Methods and Materials: All consecutive Tx candidates with PAH (except PAH due to congenital shunts) without RVF at their first evaluation (2006-2010) were included in the study. At selection, after exercise testing and NT-proBNP measurement, patients underwent echocardiography with tissue Doppler and strain imaging. Examinations were repeated at each follow-up. Collected data were tested for ability to predict time course of RV function and Tx-free patient survival. Results: Of 64 studied patients, 22 developed RVF. The 5-year Tx-free survival with and without RV worsening was 89% and 30%, respectively (po0.001). Comparing the initial data from patients with and without subsequent RV worsening we found no differences in RV size, RVEF, pulmonary arterial pressure, right atrial size or tricuspid annulus systolic excursion. However, those with subsequent RV worsening had initially higher NT-proBNP and lower RV DP/Dt, and strain analysis revealed higher RV systolic dyssynchrony, lower systolic afterload-corrected strain rate and higher diastolic early/late strain rate (SrE/SrA) ratio (po0.01). At certain cut-off values, DP/Dt and SrE/SrA showed the highest predictive values for Z2 year freedom from RVF (86.7 and 84.8%, respectively) and Tx-free survival (84.2 and 83.8%, respectively). Conclusions: In PAH patients referred for Tx, RV DP/Dt and certain strain parameters can predict the time course of RV function and Txfree survival. Our results suggest that these parameters can improve Tx listing decisions. 192 Indices of Right Ventricular Contractility in a Model of Chronic Pulmonary Hypertension J. Guihaire,1 F. Haddad,1 O. Mercier,1 D. Boulate,1 B. Decante,1 P. Herve,1 P. Dartevelle,1 M. Humbert,2 E. Fadel.1 1Laboratory of Surgical Research, Inserm U999, Marie Lannelongue Hospital, University of South Paris, Le Plessis Robinson, France; 2Service de ˆ ˆ Pneumologie, Inserm U999, Hopital Bicetre, University of South Paris, ˆ Le Kremlin-Bicetre, France. Purpose: Acceleration of the myocardium during isovolumic contraction (IVA) and right ventricular myocardial performance index (RVMPI) have been previously described as indices of right ventricular (RV) contractility. However they have not been validated in a model of chronic pressure overload. Methods and Materials: Chronic pulmonary hypertension (PH) was induced in pigs by ligation of the left pulmonary artery (PA) followed by weekly embolizations of the right lower lobe for 5 weeks (PH group, n¼11). Sham-operated animals were used as controls (n¼5). RV remodeling was assessed using echocardiography, conductance catheterism and stroke volume (SV) reserve following dobutamine infusion (5 mcg/kg/min). Right ventricular fractional area change (RVFAC),
tricuspid annular plane systolic excursion (TAPSE), RVMPI and IVA were used for RV systolic function assessment. Results: At 5 weeks, mean PA pressure (35⫾9 vs. 13⫾2 mm Hg, Po0.01) and PA elastance (0.90⫾0.44 vs. 0.29⫾0.06 mm Hg/ml, P¼0.01) were increased in PH animals compared to controls. Although RV elastance increased at 5 weeks in the PH group (0.55⫾0.14 vs. 0.34⫾0.06 mm Hg/ml, P¼0.007), RV-PA coupling measured by the ratio of RV to PA elastance was decreased at 5 weeks (0.68⫾0.17 vs. 1.18⫾0.18, Po0.001). RVAC, TAPSE, RVMPI and IVA were positively correlated with RV-PA coupling but not with RV elastance (R2¼0.84, Po0.001; R2¼0.62, P¼0.017; R2¼0.59, P¼0.003; R2¼0.83, Po0.001). IVA correlated with SV reserve (R2 ¼0.71, Po0.001). On multivariate analysis, IVA was independently associated with RV-PA coupling (R2¼0.83, Po0.001). Conclusions: IVA as well as RVMPI, RVFAC and TAPSE are markers of RV-PA coupling rather than RV contractility in a model of chronic PH. 193 Role of Angiogenesis in the Right Ventricle Remodeling in Response to Pulmonary Hypertension P.E. Noly,1,2 F. Haddad,1,2 O. Mercier,1,2 P. Dorfmuller,1,2 B. Decante,1,2 P. Dartevelle,1,2 E. Fadel.1,2 1Surgical Research Lab, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; 2 INSERM U999, Le Plessis Robinson, France. Purpose: Right ventricular (RV) remodeling consisting of RV hypertrophy and increase in contractility occurs in response to pulmonary hypertension (PH) In congenital heart disease (CHD), the right ventricle remains compensated longer than in other types of PH. We hypothesized that better matched myocardial angiogenesis contributes to delay the transition to RV failure in CHD. Methods and Materials: We induced chronic PH over a 20 weeks period in a Shunt group (n¼5) by creating an aorto to pulmonary shunt and in an chronic thromboembolic PH (CTEPH group, n¼5) by ligating the left pulmonary artery (PA) followed by weekly embolizations of the right lower lobe for weekly. In the Sham group (n¼5), the pigs were studied 20 weeks after a left PA dissection. We assessed hemodynamics using right heart catherterization and RV structural and functional remodeling using echocardiography and pressure-volume loops measurement. Myocaridal angiogenesis of the RV was studied by measuring capillary density. Results: At 20 weeks, mean PA pressure (26.8 ⫾ 1.4 mm Hg vs 22.8 ⫾0.9 mm Hg, p¼NS) and RV stroke work (SW) (2192⫾ 255 mmHg/ml vs 2110 ⫾211 mmHg/ml, p¼NS) were not significantly different in the CTEPH and Shunt groups but significantly more elevated when compared to the Sham group (14.8 ⫾ 0.8 mm Hg and 1124⫾44 mmHg/ml, respectively; po0.01). Although RV wall thickness was similarly increased in both PH groups when compared to Sham (po0.001), TAPSE and RVFAC values were only decreased in CTEPH animals (po0.05). Similarly, the RV elastance was significantly increased ( p o0,05) and the ventriculo-arterial coupling was decreased ( po 0,05) only in the CTEPH group. Although the cardiomyocyte diameter was similarly increased in both P groups (po0.05), the capillary density was only increased in the Shunt group (po0.05). Conclusions: In PH induced by systemic to pulmonary shunt, the transition from RV compensated hypertrophy to RV failure is delayed compared to similar PH in a CTEPH model. Myocardial capillary density appears to be preserved in the right ventricle of shunt models. 194 Right Ventricular Support for Pulmonary Arterial Hypertension: An Acute Feasibility Study in Sheep T. Verbelen,1 J. Verhoeven,1 M. Ghoda,1 I. Van Tichelen,1 M. Delcroix,2 F. Rega,1 B. Meyns.1 1Experimental Cardiac Surgery, KULeuven, Leuven, Belgium; 2Pneumology, University Hospitals Leuven, Leuven, Belgium. Purpose: Mechanical support of the failing right ventricle (RV) can be a life-saving option in patients with pulmonary hypertension. Since the