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Right Ventricular Dysfunction in Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Hemodynamic Analysis of the SHould we emergently revascularize Occluded Coronaries for Cardiogenic shocK (SHOCK) Trial and Registry
The 20th Annual Scientific Meeting
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HFSA
S39
Cardiovascular Physiology 100 Right Ventricular Dysfunction in Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Hemodynamic Analysis of the SHould we emergently revascularize Occluded Coronaries for Cardiogenic shocK (SHOCK) Trial and Registry Anuradha Lala1, Yu Guo2, Jinfeng Xu2, Richard Karas3, Stuart D. Katz2, Noam Josephy4, Daniel Burkhoff5, Navin K. Kapur3; 1The Zena and Michael A. Wiener Cardiovascular Institute at the Mount Sinai Hospital, New York, NY; 2New York University School of Medicine, New York, NY; 3The Cardiovascular Center and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA; 4Massachusetts Institute of Technology, Cambridge, MA; 5Columbia University, New York, NY Background: Mortality in cardiogenic shock associated with acute myocardial infarction (AMI-CS) remains unacceptably high. Right ventricular dysfunction (RVD) may contribute to poor clinical outcomes in this setting. Recognition of subclinical hemodynamic RVD in the catheterization laboratory may allow for earlier consideration of RV-directed therapy. Hypothesis: We hypothesized that RVD is common in patients presenting with AMI-CS and is associated with worse clinical outcomes. Methods and Results: A post hoc analysis was performed of AMI-CS patients enrolled in the SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK (SHOCK) Trial (n = 139) and Registry (n = 258). RVD was defined by a central venous pressure (CVP) > 10 mmHg, CVP/ pulmonary capillary wedge pressure (PCWP) ratio >0.63, pulmonary artery pulsatility index (PAPi) < 2.0, and right ventricular stroke work index (RVSWI) < 450 gm-m/m2. Severe RVD (S-RVD) was defined by a CVP>15 mmHg, CVP/PCWP>0.8, PAPi<1.5, and RVSWI<300 gm-m/m2. RVD and S-RVD were common in both cohorts: 23% and 15% in the Trial and 25% and 12% in the Registry respectively (Fig. 1). The Recover Right Trial recently studied the role of acute percutaneous mechanical circulatory support for RV failure, as defined by a CI<2.2L/m/m2 with ≥1 high-dose inotrope and either a CVP>15 or CVP/PCWP>0.63. Using the Recover Right RVF definition (RR-RVF), 45% (n = 63/139) of SHOCK trial patients and 38% (n = 98/ 258) of Registry patients had RR-RVF. Higher 30-day mortality was observed in patients with RR-RVF in the registry cohort (HR 1.44 (1.01,2.04), P = .04), but not in the trial cohort (HR 1.51(0.92,2.49), P = .10). Conclusions: Hemodynamically defined RVD and S-RVD are common in the setting of AMI-CS. The RR-RVF criteria may serve as a potential screening tool to identify patients requiring early intervention to treat RVD in AMI-CS.
and function, resulting in poor translation of preclinical findings into clinical efficacy. This study was designed to determine if clinical readouts can be back-translated into a rodent model of HFpEF with the aim to improve the translatability of preclinical studies. Methods: Supracoronary aortic banding (SAB) in juvenile rats results in cardiac hypertrophy and heart failure over a 9–10 week period due to slow, progressive pressure overload. SAB rats exhibit clinical phenotypes of HFpEF, as manifested by concen tric hypertrophy, increased left ventricular end diastolic pressure (LVEDP) and upper leftward shift of EDPVR, while EF/FS are preserved. LA size (maximal area) was quantified 9 weeks post-surgery using MRI. Exercise tolerance was evaluated 10 weeks post-surgery by treadmill test measuring time to exhaustion. The protocol for treadmill test consisted of a 3-min warm-up at 7 m/min, a steady acceleration from 7–27 m/ min over 30-min, followed by a constant speed of 27 m/min until exhaustion. Exhaustion was defined as rats remaining on shocking grid for over 5 sec even when being encouraged to run. Plasma BNP levels were assayed using a rat specific ELISA kit at the end of study. LA pressure and LVEDP were measured invasively to confirm HF status. Results: SAB rats exhibited significant 40–50% reduction in treadmill running time, indicating exercise intolerance. LA maximal area was increased by more than 2- fold, consistent with increased LA pressures and LVEDP. Plasma BNP levels were elevated by nearly 8-fold, indicating cardiac stress and failure (see Table). Summary and Conclusions: We successfully back-translated clinically relevant readouts into a rat model of HFpEF. The changes in treadmill running time, LA size and plasma BNP in SAB rats are robust enough to allow assessment of benefits for drug candidates. Incorporation of these readouts into future preclinical studies may improve success rate for development of novel HF therapies as they move from preclinical space to the clinic.
Parameters
Sham rats
SAB rats
Statistics
Exercise capacity (min) BNP (pg/ml) LA area (cm2) LA Pressure (mmHg) LVEDP (mmHg)
26.4 ± 1.0 7.3 ± 0.7 0.3 ± 0.01 1.5 ± 1.2 7.4 ± 0.9
13.7 ± 1.3 55.3 ± 5.8 0.71 ± 0.06 15.9 ± 4.0 23.3 ± 2.3
P < .05 P < .0001 P < .001 P < .005 P < .005
102 Relationship of Non-Invasive Parameters of Right Ventriculoarterial Coupling and Six Minute Walk Distance in Heart Failure With Preserved Ejection FractionAssociated Pulmonary Hypertension Priyanka T. Bhattacharya1, Gregory S. Troutman2, E. Wilson Grandin2, Jonathan N. Menachem2, Edo Y. Birati2, Jessica R. Golbus2, Paul R. Forfia3, Anjali Vaidya2, Jeremy A. Mazurek2; 1Mercy Hospital, Philadelphia, PA; 2Hospital of the University of Pennsylvania, Philadelphia, PA; 3Temple University Hospital, Philadelphia, PA
101 Can Clinically Relevant Readouts of Exercise Tolerance, Left Atrial Size and BNP be Back-Translated in a Rodent Model of Heart Failure With Preserved Ejection Fraction Chin-hu Huang, Shu-Yu Sun, Xiaolan Shen, Xiaoli Ping, Xuening Hong, Chunlian Zhang, Richard Kennan, Jeffrey Johnson, Leslawa Zwiercan, Huawei Zhao, Valdeci Da Cunha, Kersten Small, Jeffrey Madwed; Merck & Co., Kenilworth, NJ Introduction: In Heart Failure with preserved Ejection Fraction (HFpEF) Phase II clinical trials, the primary readouts are exercise intolerance, left atrial (LA) volume, and plasma BNP; while in phase III, it is mortality, hospitalization and quality of life. In preclinical space, efficacy is often assessed by improvements in cardiac structure
Background: Recently, tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) ratio (TAPSE/PASP), a non-invasive metric of right ventricular-pulmonary artery (RV-PA) coupling, has been shown to correlate with parameters on cardiopulmonary exercise testing (CPET), and is predictive of survival. More recently, we described a new non-invasive surrogate for RV-PA coupling, namely the right ventricular outflow tract pulsed-wave Doppler velocity time integral (RVOT-VTI) to PASP ratio (RVOT-VTI/PASP) which more closely reflects RV stroke volume and thus PA compliance (PAC). The relationship of RV-PA coupling (using TAPSE/PASP and RVOT-VTI/PASP), and six-minute walk distance (6MWD), however, has not been studied in heart failure with preserved ejection fraction-associated pulmonary hypertension (HFpEF-PH). Methods: We retrospectively identified 80 patients with HFpEF-PH as defined as mean PA pressure ≥ 25 mmHg and PCWP >15 mmHg and left ventricular ejection fraction ≥ 50%. We performed univariate and multivariate linear regression analysis to assess the relationship between 6MWD and noninvasive markers of RV-PA interaction as well as relevant demographic and clinical variables. Results: Mean age was 65.8 ± 13.4, median mean PA pressure was 41 mmHg (IQR 35–50) and mean 6MWD was 259 ± 117 m. By univariate analysis, older age, higher body mass index (BMI), and history of diabetes mellitus were associated with lower 6MWD (all P < .05). After adjustment for age, sex, BMI, DM and atrial fibrillation, age, BMI and RVOT-VTI/PASP were significant independent determinants of 6MWD (P < .05; Table). Conclusions: In HFpEF-PH, age, BMI and RV-PA coupling as assessed by RVOT-VTI/PASP are independently associated with 6MWD. Thus, 6MWD reflects the multifactorial nature of HFpEF-PH as well as the implication of RV-PA uncoupling in this population.
•
HFSA
S39
Cardiovascular Physiology 100 Right Ventricular Dysfunction in Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Hemodynamic Analysis of the SHould we emergently revascularize Occluded Coronaries for Cardiogenic shocK (SHOCK) Trial and Registry Anuradha Lala1, Yu Guo2, Jinfeng Xu2, Richard Karas3, Stuart D. Katz2, Noam Josephy4, Daniel Burkhoff5, Navin K. Kapur3; 1The Zena and Michael A. Wiener Cardiovascular Institute at the Mount Sinai Hospital, New York, NY; 2New York University School of Medicine, New York, NY; 3The Cardiovascular Center and Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA; 4Massachusetts Institute of Technology, Cambridge, MA; 5Columbia University, New York, NY Background: Mortality in cardiogenic shock associated with acute myocardial infarction (AMI-CS) remains unacceptably high. Right ventricular dysfunction (RVD) may contribute to poor clinical outcomes in this setting. Recognition of subclinical hemodynamic RVD in the catheterization laboratory may allow for earlier consideration of RV-directed therapy. Hypothesis: We hypothesized that RVD is common in patients presenting with AMI-CS and is associated with worse clinical outcomes. Methods and Results: A post hoc analysis was performed of AMI-CS patients enrolled in the SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK (SHOCK) Trial (n = 139) and Registry (n = 258). RVD was defined by a central venous pressure (CVP) > 10 mmHg, CVP/ pulmonary capillary wedge pressure (PCWP) ratio >0.63, pulmonary artery pulsatility index (PAPi) < 2.0, and right ventricular stroke work index (RVSWI) < 450 gm-m/m2. Severe RVD (S-RVD) was defined by a CVP>15 mmHg, CVP/PCWP>0.8, PAPi<1.5, and RVSWI<300 gm-m/m2. RVD and S-RVD were common in both cohorts: 23% and 15% in the Trial and 25% and 12% in the Registry respectively (Fig. 1). The Recover Right Trial recently studied the role of acute percutaneous mechanical circulatory support for RV failure, as defined by a CI<2.2L/m/m2 with ≥1 high-dose inotrope and either a CVP>15 or CVP/PCWP>0.63. Using the Recover Right RVF definition (RR-RVF), 45% (n = 63/139) of SHOCK trial patients and 38% (n = 98/ 258) of Registry patients had RR-RVF. Higher 30-day mortality was observed in patients with RR-RVF in the registry cohort (HR 1.44 (1.01,2.04), P = .04), but not in the trial cohort (HR 1.51(0.92,2.49), P = .10). Conclusions: Hemodynamically defined RVD and S-RVD are common in the setting of AMI-CS. The RR-RVF criteria may serve as a potential screening tool to identify patients requiring early intervention to treat RVD in AMI-CS.
and function, resulting in poor translation of preclinical findings into clinical efficacy. This study was designed to determine if clinical readouts can be back-translated into a rodent model of HFpEF with the aim to improve the translatability of preclinical studies. Methods: Supracoronary aortic banding (SAB) in juvenile rats results in cardiac hypertrophy and heart failure over a 9–10 week period due to slow, progressive pressure overload. SAB rats exhibit clinical phenotypes of HFpEF, as manifested by concen tric hypertrophy, increased left ventricular end diastolic pressure (LVEDP) and upper leftward shift of EDPVR, while EF/FS are preserved. LA size (maximal area) was quantified 9 weeks post-surgery using MRI. Exercise tolerance was evaluated 10 weeks post-surgery by treadmill test measuring time to exhaustion. The protocol for treadmill test consisted of a 3-min warm-up at 7 m/min, a steady acceleration from 7–27 m/ min over 30-min, followed by a constant speed of 27 m/min until exhaustion. Exhaustion was defined as rats remaining on shocking grid for over 5 sec even when being encouraged to run. Plasma BNP levels were assayed using a rat specific ELISA kit at the end of study. LA pressure and LVEDP were measured invasively to confirm HF status. Results: SAB rats exhibited significant 40–50% reduction in treadmill running time, indicating exercise intolerance. LA maximal area was increased by more than 2- fold, consistent with increased LA pressures and LVEDP. Plasma BNP levels were elevated by nearly 8-fold, indicating cardiac stress and failure (see Table). Summary and Conclusions: We successfully back-translated clinically relevant readouts into a rat model of HFpEF. The changes in treadmill running time, LA size and plasma BNP in SAB rats are robust enough to allow assessment of benefits for drug candidates. Incorporation of these readouts into future preclinical studies may improve success rate for development of novel HF therapies as they move from preclinical space to the clinic.
Parameters
Sham rats
SAB rats
Statistics
Exercise capacity (min) BNP (pg/ml) LA area (cm2) LA Pressure (mmHg) LVEDP (mmHg)
26.4 ± 1.0 7.3 ± 0.7 0.3 ± 0.01 1.5 ± 1.2 7.4 ± 0.9
13.7 ± 1.3 55.3 ± 5.8 0.71 ± 0.06 15.9 ± 4.0 23.3 ± 2.3
P < .05 P < .0001 P < .001 P < .005 P < .005
102 Relationship of Non-Invasive Parameters of Right Ventriculoarterial Coupling and Six Minute Walk Distance in Heart Failure With Preserved Ejection FractionAssociated Pulmonary Hypertension Priyanka T. Bhattacharya1, Gregory S. Troutman2, E. Wilson Grandin2, Jonathan N. Menachem2, Edo Y. Birati2, Jessica R. Golbus2, Paul R. Forfia3, Anjali Vaidya2, Jeremy A. Mazurek2; 1Mercy Hospital, Philadelphia, PA; 2Hospital of the University of Pennsylvania, Philadelphia, PA; 3Temple University Hospital, Philadelphia, PA
101 Can Clinically Relevant Readouts of Exercise Tolerance, Left Atrial Size and BNP be Back-Translated in a Rodent Model of Heart Failure With Preserved Ejection Fraction Chin-hu Huang, Shu-Yu Sun, Xiaolan Shen, Xiaoli Ping, Xuening Hong, Chunlian Zhang, Richard Kennan, Jeffrey Johnson, Leslawa Zwiercan, Huawei Zhao, Valdeci Da Cunha, Kersten Small, Jeffrey Madwed; Merck & Co., Kenilworth, NJ Introduction: In Heart Failure with preserved Ejection Fraction (HFpEF) Phase II clinical trials, the primary readouts are exercise intolerance, left atrial (LA) volume, and plasma BNP; while in phase III, it is mortality, hospitalization and quality of life. In preclinical space, efficacy is often assessed by improvements in cardiac structure
Background: Recently, tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) ratio (TAPSE/PASP), a non-invasive metric of right ventricular-pulmonary artery (RV-PA) coupling, has been shown to correlate with parameters on cardiopulmonary exercise testing (CPET), and is predictive of survival. More recently, we described a new non-invasive surrogate for RV-PA coupling, namely the right ventricular outflow tract pulsed-wave Doppler velocity time integral (RVOT-VTI) to PASP ratio (RVOT-VTI/PASP) which more closely reflects RV stroke volume and thus PA compliance (PAC). The relationship of RV-PA coupling (using TAPSE/PASP and RVOT-VTI/PASP), and six-minute walk distance (6MWD), however, has not been studied in heart failure with preserved ejection fraction-associated pulmonary hypertension (HFpEF-PH). Methods: We retrospectively identified 80 patients with HFpEF-PH as defined as mean PA pressure ≥ 25 mmHg and PCWP >15 mmHg and left ventricular ejection fraction ≥ 50%. We performed univariate and multivariate linear regression analysis to assess the relationship between 6MWD and noninvasive markers of RV-PA interaction as well as relevant demographic and clinical variables. Results: Mean age was 65.8 ± 13.4, median mean PA pressure was 41 mmHg (IQR 35–50) and mean 6MWD was 259 ± 117 m. By univariate analysis, older age, higher body mass index (BMI), and history of diabetes mellitus were associated with lower 6MWD (all P < .05). After adjustment for age, sex, BMI, DM and atrial fibrillation, age, BMI and RVOT-VTI/PASP were significant independent determinants of 6MWD (P < .05; Table). Conclusions: In HFpEF-PH, age, BMI and RV-PA coupling as assessed by RVOT-VTI/PASP are independently associated with 6MWD. Thus, 6MWD reflects the multifactorial nature of HFpEF-PH as well as the implication of RV-PA uncoupling in this population.