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Regional Right Ventricular Myocardial Strain by Echocardiographic Speckle Tracking Distinguishes Clinical and Hemodynamic RV Dysfunction in Pulmonary Hypertension
The 12th Annual Scientific Meeting
HFSA
S17
Pittsburgh, Pittsburgh, PA; 2Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; 3Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA; 4Department of Cardiovascular and Respiratory Diseases, ‘‘La Sapienza’’ University of Rome, Rome, Italy
Conclusions: PH is common and severe in HFpEF from the community. While age and passive pulmonary venous congestion (i.e. PVH) contribute to increasing pulmonary pressures, a reactive pulmonary vascular component (i.e. PAH) may also lead to more severe PH in HFpEF patients. The potent effect of PH on mortality lends support for therapies aimed at PAH in HFpEF.
Background: Pulmonary hypertension (PH)-induced right ventricular (RV) dysfunction confers poor prognosis. We hypothesized that peak RV longitudinal myocardial strain (LMS) quantified by 2-dimensional echocardiographic speckle tracking could identify clinically and hemodynamically significant RV dysfunction. Methods: Twenty-eight patients (age 48 6 11; 71% female) referred for evaluation of PH were studied. Patients underwent standard echocardiography and right heart catheterization. Patients with pulmonary capillary wedge pressure O 15 mm Hg were excluded. Speckle tracking was applied to routine apical 4-chamber images to calculate LMS from multiple points averaged to 6 standard segments, of which the mid RV free wall (RVFW) was used for this analysis. Four patients evaluated had normal pulmonary arterial (PA) pressures. Results: RVFW LMS was significantly decreased in PH patients compared with patients with normal PA pressure, e17 6 6% vs. e28 6 1%, P ! 0.001. RVFW LMS correlated well with RV fractional area change (FAC), mean PA pressure (MPAP), transpulmonary gradient (TPG), right atrial pressure (RAP), pulmonary vascular resistance (PVR), and cardiac index (CI) (R 5 0.81, 0.73, 0.72, 0.65, 0.60, 0.52, respectively, all P ! 0.001). RVFW LMS was significantly associated with WHO functional group (e25.4 6 4.9%, e21.2 6 7.9%, e17.4 6 6.3%, e13.4 6 4.9%, for groups I-IV respectively, P 5 0.03) while RV FAC was not (34 6 11%, 32 6 11%, 28 6 8%, 21 6 6%, for groups I-IV respectively, P 5 NS). ROC curves yielded a RVFW LMS cutpoint of e20% by multiple parameters (sensitivity/specificity/AUC: 84%/ 89%/0.92, 100%/75%/0.97, 100%/54%/0.87, 93%/77%/0.87, for MPAP O 35 mm Hg, RAP O 10 mm Hg, CI ! 2 L/min/m2, PVR O 6 Wood units, respectively). Conclusions: Regional RVFW LMS calculated by speckle tracking can be used to assess RV function in PH. It appears to discriminate physiological and functional RV dysfunction and may be a link between the two.
047 Kidney-Heart Connection: Experimental Mild Renal Insufficiency Induces Early Cardiac Fibrosis and Myocardial Diastolic Dysfunction Followed by Late Systolic Failure Fernando L. Martin1, Josef Korinek1, Brenda K. Huntley1, Elise A. Oehler1, Gerald E. Harders1, Alessandro Cataliotti1, Horng H. Chen1, John C. Burnett1; 1Cardiorenal Research, Mayo Clinic, Rochester, MN Reduced renal function (fx) increases CV morbidity and mortality by unclear mechanisms. We have reported mild reduction in renal fx produced by unilateral nephrectomy (NX) increases myocardial collagen content and widespread alterations in ventricular gene profiles in absence of hypertension (HTN) or volume overload (VO) underscoring a kidney-heart connection in the control of myocardial structure. We now hypothesize that such alterations in ventricular structure are associated with early changes in myocardial fx and that the development of early cardiac fibrosis is progressive. Methods:Cardiorenal fx and structure were assessed in Wistar rats [sham (S; n 5 10) and NX(n 5 9)] 4 weeks (wk) after NX. At wk 4 GFR, Na and water excretion, and plasma BNP, renin activity (PRA), and aldosterone (Aldo) were assessed. LV mass, EF, circumferential systolic strain (Cs) and,early (Csr-E) and late (Csr-A) diastolic strain rates and ratio were assessed by echo speckle tracking. At wk 16 in separate groups [S; n 5 10 and NX; n 5 9] LV structure and fx and cardiac fibrosis [Picrosirius Red staining, (PRS)] was also determined. Results: At wk 4, glomerular hypertrophy was observed in NX (p ! 0.001) and GFR tended to decrease. Na and water excretions were not different between groups with no activation of PRA, Aldo or BNP. Blood pressure (BP), EF, LV mass, Cs did not differ between the groups. However, Csr-E and Csr-E/A ratio were significantly lower in NX group (S:6.4 6 0.5,NX:5.2 6 0.8 and S:1.8 6 0.5,NX:1.2 6 0.4;p ! 0.05) consistent with diastolic dysfunction (DD). PRS in LV of NX compared to S revealed greater fibrosis (S:2.4 6 0.1, NX:4.2 6 0.4%,p ! 0.001). At wk 16, LV mass was significantly higher in NX (S: 1.0 6 0.1, NX: 1.3 6 0.3 g,p ! 0.001), with a mild decrease in EF (S: 79 6 4, NX: 74 6 3, p ! 0.005), Cs (S: 19.8 6 2.8, NX: 16.2 6 1.8, p ! 0.005), and further decrease of Csr-E and Csr-E/A ratio (S:5.7 6 1.3, NX:4.5 6 0.6, and S: 1.52 6 0.37, NX: 0.98 6 0.4; p ! 0.05). There was persistent fibrosis (S:2.1 6 0.1, NX:4.4 6 0.4 %,p ! 0.001). Conclusion: Even mild renal insufficiency produced by NX results in early cardiac fibrosis and myocardial DD independent of neurohumoral activation, HTN, or VO. At 16 wk, there is progressive deterioration of diastolic and systolic fx with LV hypertrophy. These studies support a kidney - heart connection in early renal dysfunction resulting in progressive ventricular dysfunction, remodeling and fibrosis.
049 Abnormal Contractile Reserve Limits Exercise Capacity in Heart Failure with Preserved EF Barry A. Borlaug1, Thomas P. Olson1, Kelly S. Flood1, Bruce D. Johnson1, Margaret M. Redfield1; 1Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN Background: Patients with heart failure and preserved ejection fraction (HFpEF) have abnormal contractile responses with maximal exercise, yet it remains unknown whether this is due to impaired inotropic reserve or simply differences in peak workload achieved. Objectives: To compare ventricular-vascular function at rest and during matched submaximal and peak exercise in patients with HFpEF and hypertension (HTN). Methods: Age and gender matched subjects with HFpEF (n 5 18) and HTN (n 5 11) underwent maximal metabolic exercise testing with echo-Doppler hemodynamic assessment. Load-independent contractility was assessed by peak power index (PWR/EDV), single beat end systolic elastance (Ees), and preload recruitable stroke work (PRSW). Afterload was determined by arterial elastance (Ea) and systemic vascular resistance (SVR). Dynamic ventricular-arterial interaction was assessed by the coupling ratio (Ea/Ees), and heart rate reserve (HRR) with exercise was determined. Results: Baseline hemodynamics were similar (Table). Exercise capacity was reduced in HFpEF (peak VO2 12.7 6 3.0 vs 18.6 6 3.7 ml/kg*min, p ! 0.0001). The exercise-induced augmentation in contractility was markedly blunted in HFpEF subjects, both at matched low level and peak workloads. HFpEF displayed less vasodilation and lower HRR (56 6 16 vs 81 6 23%, p 5 0.002). Peak exercise capacity was significantly associated with contractile reserve (r 5 0.7, p 5 0.0001). Conclusions: Patients with HFpEF display impaired contractile reserve at both low level and peak exercise, in addition to abnormal heart rate and vascular responses. Therapies targeting systolic reserve function may prove useful in the treatment of HFpEF.
Baseline
048 Regional Right Ventricular Myocardial Strain by Echocardiographic Speckle Tracking Distinguishes Clinical and Hemodynamic RV Dysfunction in Pulmonary Hypertension Manuela Reali1,4, Navin Rajagopalan1, Angel Lopez-Candales1, Kevin E. Cordero1, Matthew Suffoletto1, Sanjeev G. Shroff3, Michael R. Pinsky1,3,4, John Gorcsan1, Michael A. Mathier1, Marc A. Simon1,3; 1Cardiovascular Institute, University of
Ees (mmHg/ml) PWR/EDV (mmHg/s) PRSW (gm/cm2) Ea (mmHg/ml) SVR (DSC) Ea/Ees CO (L/min)
Change at 20 Watts Exercise
Change at Peak Exercise
HTN
HFpEF
HTN
HFpEF
HTN
HFpEF
1.8 6 0.4 350 6 70 76 6 15 2.2 6 0.6 1900 6 430 1.2 6 0.2 4.4 6 1.5
1.7 6 0.8 330 6 70 82 6 45 1.8 6 0.6 1570 6 530 1.1 6 0.4 4.8 6 1.3
0.7 6 0.6 100 6 50 22 6 8 e0.5 6 0.3 e810 6 290 e0.6 6 0.2 3.4 6 1.2
0.1 6 0.6** 20 6 80** 9 6 12y e0.2 6 0.4 e520 6 370** e0.2 6 0.4** 2.2 6 0.7y
2.4 6 1.1 410 6 90 57 6 13 e0.1 6 0.5 e1000 6 350 e0.7 6 0.2 7.5 6 2.5
0.7 6 0.9* 130 6 120* 29 6 21* 0.2 6 0.5 e610 6 370y e0.2 6 0.5y 4.3 6 2.2*
*p ! 0.001, yp ! 0.01, **p ! 0.05
HFSA
S17
Pittsburgh, Pittsburgh, PA; 2Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; 3Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA; 4Department of Cardiovascular and Respiratory Diseases, ‘‘La Sapienza’’ University of Rome, Rome, Italy
Conclusions: PH is common and severe in HFpEF from the community. While age and passive pulmonary venous congestion (i.e. PVH) contribute to increasing pulmonary pressures, a reactive pulmonary vascular component (i.e. PAH) may also lead to more severe PH in HFpEF patients. The potent effect of PH on mortality lends support for therapies aimed at PAH in HFpEF.
Background: Pulmonary hypertension (PH)-induced right ventricular (RV) dysfunction confers poor prognosis. We hypothesized that peak RV longitudinal myocardial strain (LMS) quantified by 2-dimensional echocardiographic speckle tracking could identify clinically and hemodynamically significant RV dysfunction. Methods: Twenty-eight patients (age 48 6 11; 71% female) referred for evaluation of PH were studied. Patients underwent standard echocardiography and right heart catheterization. Patients with pulmonary capillary wedge pressure O 15 mm Hg were excluded. Speckle tracking was applied to routine apical 4-chamber images to calculate LMS from multiple points averaged to 6 standard segments, of which the mid RV free wall (RVFW) was used for this analysis. Four patients evaluated had normal pulmonary arterial (PA) pressures. Results: RVFW LMS was significantly decreased in PH patients compared with patients with normal PA pressure, e17 6 6% vs. e28 6 1%, P ! 0.001. RVFW LMS correlated well with RV fractional area change (FAC), mean PA pressure (MPAP), transpulmonary gradient (TPG), right atrial pressure (RAP), pulmonary vascular resistance (PVR), and cardiac index (CI) (R 5 0.81, 0.73, 0.72, 0.65, 0.60, 0.52, respectively, all P ! 0.001). RVFW LMS was significantly associated with WHO functional group (e25.4 6 4.9%, e21.2 6 7.9%, e17.4 6 6.3%, e13.4 6 4.9%, for groups I-IV respectively, P 5 0.03) while RV FAC was not (34 6 11%, 32 6 11%, 28 6 8%, 21 6 6%, for groups I-IV respectively, P 5 NS). ROC curves yielded a RVFW LMS cutpoint of e20% by multiple parameters (sensitivity/specificity/AUC: 84%/ 89%/0.92, 100%/75%/0.97, 100%/54%/0.87, 93%/77%/0.87, for MPAP O 35 mm Hg, RAP O 10 mm Hg, CI ! 2 L/min/m2, PVR O 6 Wood units, respectively). Conclusions: Regional RVFW LMS calculated by speckle tracking can be used to assess RV function in PH. It appears to discriminate physiological and functional RV dysfunction and may be a link between the two.
047 Kidney-Heart Connection: Experimental Mild Renal Insufficiency Induces Early Cardiac Fibrosis and Myocardial Diastolic Dysfunction Followed by Late Systolic Failure Fernando L. Martin1, Josef Korinek1, Brenda K. Huntley1, Elise A. Oehler1, Gerald E. Harders1, Alessandro Cataliotti1, Horng H. Chen1, John C. Burnett1; 1Cardiorenal Research, Mayo Clinic, Rochester, MN Reduced renal function (fx) increases CV morbidity and mortality by unclear mechanisms. We have reported mild reduction in renal fx produced by unilateral nephrectomy (NX) increases myocardial collagen content and widespread alterations in ventricular gene profiles in absence of hypertension (HTN) or volume overload (VO) underscoring a kidney-heart connection in the control of myocardial structure. We now hypothesize that such alterations in ventricular structure are associated with early changes in myocardial fx and that the development of early cardiac fibrosis is progressive. Methods:Cardiorenal fx and structure were assessed in Wistar rats [sham (S; n 5 10) and NX(n 5 9)] 4 weeks (wk) after NX. At wk 4 GFR, Na and water excretion, and plasma BNP, renin activity (PRA), and aldosterone (Aldo) were assessed. LV mass, EF, circumferential systolic strain (Cs) and,early (Csr-E) and late (Csr-A) diastolic strain rates and ratio were assessed by echo speckle tracking. At wk 16 in separate groups [S; n 5 10 and NX; n 5 9] LV structure and fx and cardiac fibrosis [Picrosirius Red staining, (PRS)] was also determined. Results: At wk 4, glomerular hypertrophy was observed in NX (p ! 0.001) and GFR tended to decrease. Na and water excretions were not different between groups with no activation of PRA, Aldo or BNP. Blood pressure (BP), EF, LV mass, Cs did not differ between the groups. However, Csr-E and Csr-E/A ratio were significantly lower in NX group (S:6.4 6 0.5,NX:5.2 6 0.8 and S:1.8 6 0.5,NX:1.2 6 0.4;p ! 0.05) consistent with diastolic dysfunction (DD). PRS in LV of NX compared to S revealed greater fibrosis (S:2.4 6 0.1, NX:4.2 6 0.4%,p ! 0.001). At wk 16, LV mass was significantly higher in NX (S: 1.0 6 0.1, NX: 1.3 6 0.3 g,p ! 0.001), with a mild decrease in EF (S: 79 6 4, NX: 74 6 3, p ! 0.005), Cs (S: 19.8 6 2.8, NX: 16.2 6 1.8, p ! 0.005), and further decrease of Csr-E and Csr-E/A ratio (S:5.7 6 1.3, NX:4.5 6 0.6, and S: 1.52 6 0.37, NX: 0.98 6 0.4; p ! 0.05). There was persistent fibrosis (S:2.1 6 0.1, NX:4.4 6 0.4 %,p ! 0.001). Conclusion: Even mild renal insufficiency produced by NX results in early cardiac fibrosis and myocardial DD independent of neurohumoral activation, HTN, or VO. At 16 wk, there is progressive deterioration of diastolic and systolic fx with LV hypertrophy. These studies support a kidney - heart connection in early renal dysfunction resulting in progressive ventricular dysfunction, remodeling and fibrosis.
049 Abnormal Contractile Reserve Limits Exercise Capacity in Heart Failure with Preserved EF Barry A. Borlaug1, Thomas P. Olson1, Kelly S. Flood1, Bruce D. Johnson1, Margaret M. Redfield1; 1Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN Background: Patients with heart failure and preserved ejection fraction (HFpEF) have abnormal contractile responses with maximal exercise, yet it remains unknown whether this is due to impaired inotropic reserve or simply differences in peak workload achieved. Objectives: To compare ventricular-vascular function at rest and during matched submaximal and peak exercise in patients with HFpEF and hypertension (HTN). Methods: Age and gender matched subjects with HFpEF (n 5 18) and HTN (n 5 11) underwent maximal metabolic exercise testing with echo-Doppler hemodynamic assessment. Load-independent contractility was assessed by peak power index (PWR/EDV), single beat end systolic elastance (Ees), and preload recruitable stroke work (PRSW). Afterload was determined by arterial elastance (Ea) and systemic vascular resistance (SVR). Dynamic ventricular-arterial interaction was assessed by the coupling ratio (Ea/Ees), and heart rate reserve (HRR) with exercise was determined. Results: Baseline hemodynamics were similar (Table). Exercise capacity was reduced in HFpEF (peak VO2 12.7 6 3.0 vs 18.6 6 3.7 ml/kg*min, p ! 0.0001). The exercise-induced augmentation in contractility was markedly blunted in HFpEF subjects, both at matched low level and peak workloads. HFpEF displayed less vasodilation and lower HRR (56 6 16 vs 81 6 23%, p 5 0.002). Peak exercise capacity was significantly associated with contractile reserve (r 5 0.7, p 5 0.0001). Conclusions: Patients with HFpEF display impaired contractile reserve at both low level and peak exercise, in addition to abnormal heart rate and vascular responses. Therapies targeting systolic reserve function may prove useful in the treatment of HFpEF.
Baseline
048 Regional Right Ventricular Myocardial Strain by Echocardiographic Speckle Tracking Distinguishes Clinical and Hemodynamic RV Dysfunction in Pulmonary Hypertension Manuela Reali1,4, Navin Rajagopalan1, Angel Lopez-Candales1, Kevin E. Cordero1, Matthew Suffoletto1, Sanjeev G. Shroff3, Michael R. Pinsky1,3,4, John Gorcsan1, Michael A. Mathier1, Marc A. Simon1,3; 1Cardiovascular Institute, University of
Ees (mmHg/ml) PWR/EDV (mmHg/s) PRSW (gm/cm2) Ea (mmHg/ml) SVR (DSC) Ea/Ees CO (L/min)
Change at 20 Watts Exercise
Change at Peak Exercise
HTN
HFpEF
HTN
HFpEF
HTN
HFpEF
1.8 6 0.4 350 6 70 76 6 15 2.2 6 0.6 1900 6 430 1.2 6 0.2 4.4 6 1.5
1.7 6 0.8 330 6 70 82 6 45 1.8 6 0.6 1570 6 530 1.1 6 0.4 4.8 6 1.3
0.7 6 0.6 100 6 50 22 6 8 e0.5 6 0.3 e810 6 290 e0.6 6 0.2 3.4 6 1.2
0.1 6 0.6** 20 6 80** 9 6 12y e0.2 6 0.4 e520 6 370** e0.2 6 0.4** 2.2 6 0.7y
2.4 6 1.1 410 6 90 57 6 13 e0.1 6 0.5 e1000 6 350 e0.7 6 0.2 7.5 6 2.5
0.7 6 0.9* 130 6 120* 29 6 21* 0.2 6 0.5 e610 6 370y e0.2 6 0.5y 4.3 6 2.2*
*p ! 0.001, yp ! 0.01, **p ! 0.05