Month: August 2022
Dr. L. Christian Napp, Hannover Medical School
Dr. Jason Williams, Ocean Springs Hospital
Dr. Jaime Hernandez-Montfort, UTMB Health
Dr. Bart Meyns, KU Leuven
Jane Wilcox, MD | Northwestern University
Dr. Navin Kapur, Tufts Medical Center
Dr. Bernhard Schieffer, University Hospital Giessen and Marburg
Lija Swain, PhD | Tufts Medical Center
Tomoki Sakata, MD | Mt. Sinai
Dr. Carsten Tschöpe, Charite, CVK
Div Verma, MD | Yavapai Regional Medical Center
David Joyce, MD | Medical College of Wisconsin
Dr. Alexander Bernhardt, University Hospital Hamburg-Eppendorf
Enrico Romagnoli, MD | Gemelli University Hospital
Dr. Bill O’Neill, Henry Ford Hospital
Peter Frederiksen, MD | University of Southern Denmark
Sebastian Billig, MD | University Hospital Aachen
Opening Lecture: Dan Burkhoff, MD | Columbia University
A-CURE 2020 Highlights
2020 A-CURE Program
Bill O’Neill, MD | Henry Ford Health System
Bob Kloner | Huntington Medical Research Institute & Kiyo Ishikawa | Icahn School of Medicine
Elric Zweck | Heinrich-Heine University, Dusseldorf
Herman Reichenspurner | University Hospital Hamburg-Eppendorf
Prof. Dr. med. Carsten Tschöpe, Charité, CVK: Ventricular Unloading and Inflammation – The Role of Impella in Myocarditis
Mark Anderson | Hackensack Meridian School of Medicine
Left ventricular support by catheter-mounted axial flow pump reduces infarct size
Meyns, B., Stolinski, J., Leunens, V., Verbeken, E., Flameng, W
Abstract
OBJECTIVES: We sought to investigate the effect of a catheter-mounted microaxial blood pump (Impella, Aachen, Germany) on myocardial infarct size. BACKGROUND: The small rotary blood pump Impella provides unloading of the left ventricle and is introducible via the femoral artery. METHODS: Myocardial infarction was induced by occlusion of major branches of the left anterior descending coronary artery for 60 min followed by 120 min of reperfusion in 26 sheep. The animals were allocated to four groups: group 1 had no support; group 2 was fully supported with the pump during ischemia and reperfusion; group 3 was supported during reperfusion only; and group 4 was partially supported during reperfusion. Infarct size, hemodynamics, myocardial oxygen consumption, lactate extraction, and myocardial flow were analyzed. RESULTS: Infarct size was significantly reduced in the pump-supported animals (percent area at risk in group 1: 67.2 +/- 4.6%; group 2: 18.1 +/- 10%; group 3: 41.6 +/- 5.8%; group 4: 54 +/- 8%; p = 0.00001). The pump produced 4.1 +/- 0.1 l/min at full support and 2.4 +/- 0.1 l/min at partial support. The pump significantly increased the diastolic and mean blood pressures (groups 2, 3, and 4) and significantly decreased the left ventricular end-diastolic pressure (groups 2 and 3). During ischemia, myocardial flow was not influenced by pump support. At reperfusion, the fully supported group had significantly higher myocardial flow. Pump support reduced myocardial oxygen consumption significantly, and this reduction correlates strongly with the reduction in infarct size (r = 0.9). CONCLUSIONS: Support by a microaxial blood pump reduces myocardial oxygen consumption during ischemia and reperfusion and leads to a reduction of infarct size. This reduction in infarct size correlates with the degree of unloading during reperfusion.
Navin Kapur | Tufts Medical Center
Zach George | University of South Carolina
Early Assistance With Left Ventricular Assist Device Limits Left Ventricular Remodeling After Acute Myocardial Infarction in a Swine Model
Sun, X., Li, J., Zhao, W., Lu, S., Guo, C., Lai, H., Wang, C.
Abstract
Although left ventricular assist devices (LVADs) have been commonly used for patients with cardiogenic shock after acute myocardial infarction (AMI), their effects on post-AMI prognosis remain to be elucidated. In this study, we aimed to explore the effects of an LVAD on left ventricular (LV) remodeling and function at the postinfarction stage in a swine model. AMI was induced by ligation of the circumflex artery or its branches for 120 min, followed by 120 min of reperfusion. In the assist group (n = 6), LVAD was initiated at 90 min after ischemia and was maintained for support until 120 min after reperfusion, whereas the control group (n = 6) received no support. LV pressure, volume, wall stress, and stroke work were all decreased by LVAD assistance at the ischemia and reperfusion stages, and blood pressure and cardiac output were maintained. All swine were studied 1 month after the procedure, and those in the assist group showed less increased end-diastolic volumes (assist vs. control: 57.9 ± 6.6 vs. 79.0 ± 6.7 mL, P = 0.032) and sphericity (assist vs. control: 1.33 ± 0.16 vs. 1.51 ± 0.12, P = 0.01), as well as improved ejection fractions (assist vs. control: 59.0 ± 7.8 vs. 42.3 ± 6.0%, P = 0.002). Furthermore, despite a presence of a similar initial ischemic area, the percent of infarcted myocardium was reduced by 49.9% in the assist group (assist vs. control: 18.1 ± 4.8 vs. 35.3 ± 6.2%, P < 0.001). These results suggested that early assistance with an LVAD in AMI limited LV remodeling, preserved postinfarction systolic function, and improved the prognosis.
Dan Burkhoff | Columbia
Jakob Josiassen | Copenhagen University Hospital: Abstract Finalist
Kay Everett | Beth Israel Deaconess Medical Center: Abstract Finalist
Lija Swain | Tufts Medical Center: Abstract Finalist
Left Ventricular Unloading Using an Impella CP Improves Coronary Flow and Infarct Zone Perfusion in Ischemic Heart Failure
Abstract
Background-—Delivering therapeutic materials, like stem cells or gene vectors, to the myocardium is difficult in the setting of
ischemic heart failure because of decreased coronary flow and impaired microvascular perfusion (MP). The aim of this study was to
determine if mechanical left ventricular (LV) unloading with the Impella increases coronary flow and MP in a subacute myocardial
infarction.
Methods and Results-—Anterior transmural myocardial infarction (infarct size, 26.03.4%) was induced in Yorkshire pigs. At 2
weeks after myocardial infarction, 6 animals underwent mechanical LV unloading by Impella, whereas 4 animals underwent
pharmacological LV unloading using sodium nitroprusside for 2 hours. LV unloading with Impella significantly reduced end-diastolic
volume (1611mL, P=0.02) and end-diastolic pressure (EDP; 3223 mm Hg, P=0.03), resulting in a significant decrease in LV
end-diastolic wall stress (EDWS) (infarct: 71.614.7 to 43.310.8 kdynes/cm2 [P=0.02]; remote: 66.620.9 to 40.613.3 kdynes/
cm2 [P=0.02]). Coronary flow increased immediately and remained elevated after 2 hours in Impella-treated pigs. Compared
with the baseline, MP measured by fluorescent microspheres significantly increased within the infarct zone (10981%, P=0.003),
but not in the remote zone. Although sodium nitroprusside effectively reduced LV-EDWS, 2 (50%) of sodium nitroprusside–treated
pigs developed profound systemic hypotension. A significant correlation was observed between the infarct MP and EDWS (r2=0.43,
P=0.03), suggesting an important role of EDWS in regulating MP during LV unloading in the infarcted myocardium.
Conclusions-—LV unloading using an Impella decreased EDWS and increased infarct MP without hemodynamic decompensation.
Mechanical LV unloading is a novel and efficient approach to increase infarct MP in patients with subacute myocardial infarction.
Left Ventricular Mechanical Unloading by Total Support of Impella in Myocardial Infarction Reduces Infarct Size, Preserves Left Ventricular Function, and Prevents Subsequent Heart Failure in Dogs
Keita Saku, Takamori Kakino, Takahiro Arimura, Genya Sunagawa, Takuya Nishikawa, Takafumi Sakamoto, Takuya Kishi, Hiroyuki Tsutsui, Kenji Sunagawa
Abstract
BACKGROUND: Acute myocardial infarction remains a leading cause of chronic heart failure. Excessive myocardial oxygen demand relative to supply is the fundamental mechanism of myocardial infarction. We thus hypothesized that left ventricular (LV) mechanical unloading by the total support of transvascular LV assist device Impella could minimize oxygen
demand, thereby reducing infarct size and preventing subsequent heart failure.
METHODS AND RESULTS: In 20 dogs, we ligated the left anterior descending coronary artery for 180 minutes and then reperfused. We introduced Impella from 60 minutes after the onset of ischemia to 60 minutes after reperfusion. In the partial support group, Impella supported 50% of total cardiac output. In the total support group, systemic flow totally depends on Impella flow. Four weeks after ischemia/reperfusion (I/R), we compared LV function and infarct size among 4 groups: sham (no I/R), I/R (no Impella support), partial support, and total support. Compared with I/R, total support lowered LV end-diastolic pressure (15.0±3.5 versus 4.7±1.7 mm Hg; P<0.001), increased LV end-systolic elastance (4.3±0.8 versus 13.9±5.1 mm Hg/mL; P<0.001), and decreased NT-proBNP (N-terminal pro-B-type natriuretic peptide) level (4081±1123 versus 1773±390 pg/mL; P<0.05). Furthermore, total support markedly reduced infarct size relative to I/R, whereas partial support decreased infarct size to a lesser extent (I/R, 16.3±2.6; partial support, 8.5±4.3; and total support, 2.1±1.6%; P<0.001).
CONCLUSIONS: LV mechanical unloading by the total support of Impella during the acute phase of myocardial infarction reduced infarct size and prevented subsequent heart failure in dogs.
Left Ventricular Unloading Using an Impella CP Improves Coronary Flow and Infarct Zone Perfusion in Ischemic Heart Failure
Shin Watanabe, MD; Kenneth Fish, PhD; Jason C. Kovacic, MD, PhD; Olympia Bikou, MD; Lauren Leonardson, LVT; Koichi Nomoto, MD;
Jaume Aguero, MD; Navin K. Kapur, MD; Roger J. Hajjar, MD; Kiyotake Ishikawa, MD
Abstract
Background-—Delivering therapeutic materials, like stem cells or gene vectors, to the myocardium is difficult in the setting of ischemic heart failure because of decreased coronary flow and impaired microvascular perfusion (MP). The aim of this study was to determine if mechanical left ventricular (LV) unloading with the Impella increases coronary flow and MP in a subacute myocardial infarction.
Methods and Results-—Anterior transmural myocardial infarction (infarct size, 26.03.4%) was induced in Yorkshire pigs. At 2 weeks after myocardial infarction, 6 animals underwent mechanical LV unloading by Impella, whereas 4 animals underwent pharmacological LV unloading using sodium nitroprusside for 2 hours. LV unloading with Impella significantly reduced end-diastolic volume (1611%, P=0.02) and end-diastolic pressure (EDP; 3223%, P=0.03), resulting in a significant decrease in LV enddiastolic wall stress (EDWS) (infarct: 71.614.7 to 43.310.8 kdynes/cm2 [P=0.02]; remote: 66.620.9 to 40.613.3 kdynes/cm2 [P=0.02]). Coronary flow increased immediately and remained elevated after 2 hours in Impella-treated pigs. Compared with the baseline, MP measured by fluorescent microspheres significantly increased within the infarct zone (10981%, P=0.003), but not in the remote zone. Although sodium nitroprusside effectively reduced LV-EDWS, 2 (50%) of sodium nitroprusside–treated pigs developed profound systemic hypotension. A significant correlation was observed between the infarct MP and EDWS (r2=0.43, P=0.03), suggesting an important role of EDWS in regulating MP during LV unloading in the infarcted myocardium.
Conclusions-—LV unloading using an Impella decreased EDWS and increased infarct MP without hemodynamic decompensation. Mechanical LV unloading is a novel and efficient approach to increase infarct MP in patients with subacute myocardial infarction.
JAHA, 2018 Journal of the American Heart Association
Left Ventricular Unloading Using an Impella CP Improves Coronary Flow and Infarct Zone Perfusion in Ischemic Heart Failure
Abstract
Background-—Delivering therapeutic materials, like stem cells or gene vectors, to the myocardium is difficult in the setting of ischemic heart failure because of decreased coronary flow and impaired microvascular perfusion (MP). The aim of this study was to determine if mechanical left ventricular (LV) unloading with the Impella increases coronary flow and MP in a subacute myocardial infarction.
Methods and Results-—Anterior transmural myocardial infarction (infarct size, 26.03.4%) was induced in Yorkshire pigs. At 2 weeks after myocardial infarction, 6 animals underwent mechanical LV unloading by Impella, whereas 4 animals underwent pharmacological LV unloading using sodium nitroprusside for 2 hours. LV unloading with Impella significantly reduced end-diastolic volume (1611%, P=0.02) and end-diastolic pressure (EDP; 3223%, P=0.03), resulting in a significant decrease in LV enddiastolic wall stress (EDWS) (infarct: 71.614.7 to 43.310.8 kdynes/cm2 [P=0.02]; remote: 66.620.9 to 40.613.3 kdynes/cm2 [P=0.02]). Coronary flow increased immediately and remained elevated after 2 hours in Impella-treated pigs. Compared with the baseline, MP measured by fluorescent microspheres significantly increased within the infarct zone (10981%, P=0.003), but not in the remote zone. Although sodium nitroprusside effectively reduced LV-EDWS, 2 (50%) of sodium nitroprusside–treated pigs developed profound systemic hypotension. A significant correlation was observed between the infarct MP and EDWS (r2=0.43, P=0.03), suggesting an important role of EDWS in regulating MP during LV unloading in the infarcted myocardium.
Conclusions-—LV unloading using an Impella decreased EDWS and increased infarct MP without hemodynamic decompensation. Mechanical LV unloading is a novel and efficient approach to increase infarct MP in patients with subacute myocardial infarction.
Circulation Heart Failure, May 2018
Left Ventricular Mechanical Unloading by Total Support of Impella in Myocardial Infarction Reduces Infarct Size, Preserves Left Ventricular Function, and Prevents Subsequent Heart Failure in Dogs
Abstract
BACKGROUND: Acute myocardial infarction remains a leading cause of chronic heart failure. Excessive myocardial oxygen demand relative to supply is the fundamental mechanism of myocardial infarction. We thus hypothesized that left ventricular (LV) mechanical unloading by the total support of transvascular LV assist device Impella could minimize oxygen
demand, thereby reducing infarct size and preventing subsequent heart failure.
METHODS AND RESULTS: In 20 dogs, we ligated the left anterior descending coronary artery for 180 minutes and then reperfused. We introduced Impella from 60 minutes after the onset of ischemia to 60 minutes after reperfusion. In the partial support group, Impella supported 50% of total cardiac output. In the total support group, systemic flow totally depends on Impella flow. Four weeks after ischemia/reperfusion (I/R), we compared LV function and infarct size among 4 groups: sham (no I/R), I/R (no Impella support), partial support, and total support. Compared with I/R, total support lowered LV end-diastolic pressure (15.0±3.5 versus 4.7±1.7 mm Hg; P<0.001), increased LV end-systolic elastance (4.3±0.8 versus 13.9±5.1 mm Hg/mL; P<0.001), and decreased NT-proBNP (N-terminal pro-B-type natriuretic peptide) level (4081±1123 versus 1773±390 pg/mL; P<0.05). Furthermore, total support markedly reduced infarct size relative to I/R, whereas partial support decreased infarct size to a lesser extent (I/R, 16.3±2.6; partial support, 8.5±4.3; and total support, 2.1±1.6%; P<0.001).
CONCLUSIONS: LV mechanical unloading by the total support of Impella during the acute phase of myocardial infarction reduced infarct size and prevented subsequent heart failure in dogs.
Dr. Babar Basir, Henry Ford Hospital
Dr. Kiyotake Ishikawa, Icahn School of Medicine at Mount Sinai
Dr. Mark Anderson, Hackensack University Medical Center
Dr. Kapildeo Lotun, University of Arizona
Total mechanical energy of a ventricle model and cardiac oxygen consumption
Suga, H.
Abstract
Mechanical energy (ENG) required by a time-varying elastance model of the ventricle was compared with oxygen consumption per beat (VO2) of the canine left ventricle contracting under a variety of loading conditions. ENG needed for this model to increase its elastance during systole is shown to be equal to the sum of the potential energy built in the elastance during systole plus the external mechanical stroke work. This ENG is equivalent to the area (PVA) bounded by the end-systolic and end-diastolic P-V curves and the systolic limb of the P-V loop trajectory in the P-V plane. There was a high correlation (r = 0.89) between VO2s documented in the literature and PVAs assessed by the author from the accompanying P-V data from both isovolumic and ejecting contractions in 11 hearts. A linear regression analysis yielded an empirical equation: VO2 (ml O2/beat) = a . PVA (mmHg . ml/beat) + b, where a = 1.37 X 10(-5) and b = 0.027, which can be used to predict VO2 from PVA. A preliminary experimental study in my laboratory confirmed the validity of this empirical equation.
Dr. Daniel Scheiber, University Hospital Dusseldorf
Relation between left ventricular oxygen consumption and pressure-volume area in conscious dogs
Dr. Ralf Westenfeld, University Hospital Dusseldorf
Effect of reduced aortic compliance on cardiac efficiency and contractile function of in situ canine left ventricle
Kelly, R. P., Tunin, R., Kass, D. A.
Abstract
This study tests the hypothesis that arterial vascular stiffening adversely influences in situ left ventricular contractile function and energetic efficiency. Ten reflex-blocked anesthetized dogs underwent a bypass operation in which a Dacron graft was sewn to the ascending aorta and connected to the infrarenal abdominal aorta via a plastic conduit. Flow was directed through either native aorta or plastic conduit by placement of vascular clamps. Arterial properties were measured from aortic pressure-flow data, and ventricular function was assessed by pressure-volume (PV) relations. Coronary sinus blood was drained via an extracorporeal circuit for direct measurement of myocardial O2 consumption (MVO2). Data at multiple steady-state preload volumes were combined to derive chamber function and energetics relations. Energetic efficiency was assessed by the inverse slope of the MVO2-PV area relation. Directing flow through plastic versus native aorta resulted in a 60-80% reduction in compliance but little change in mean resistance. Arterial pulse pressure rose from 34 to 99 mm Hg (p less than 0.001). Contractile function assessed by the end-systolic PV relation, stroke work-end-diastolic volume relation, and dP/dtmax at matched end-diastolic volume did not significantly change. However, MVO2 increased by 32% (p less than 0.01) and was matched by a rise in PV area, such that the MVO2-PV area relation and efficiency was unaltered. The MVO2 required to sustain a given stroke volume, however, increased from 20% to 40%, depending on the baseline level (p less than 0.001). Thus, whereas the contractile function and efficiency of normal hearts are not altered by ejection into a stiff vascular system, the energetic cost to the heart for maintaining adequate flow is increased. This suggests a mechanism whereby human vascular stiffening may yield little functional decrement at rest but limit reserve capacity under conditions of increased demand.
The science behind percutaneous hemodynamic support: a review and comparison of support strategies
Burkhoff, D., Naidu, S. S.
Abstract
Patients in a variety of cardiovascular disease states may benefit from temporary percutaneous cardiac support, including those in acute decompensated heart failure, fulminant myocarditis, acute myocardial infarction with or without cardiogenic shock and those undergoing high-risk percutaneous coronary intervention. The ideal percutaneous cardiac support device is safe, easy to use and versatile enough to meet the needs of various clinical situations and patient cohorts. In addition, it should provide maximal hemodynamic support and protection against myocardial ischemia. With these goals in mind, the scientific principles that govern hemodynamic effectiveness and myocardial protection as they pertain to acute support devices are reviewed.
Dr. Carlos del Rio, MyoKardia and QTest Labs
Transvalvular Ventricular Unloading Before Reperfusion in Acute Myocardial Infarction
Swain, L., et al. (2020). New approaches to limit myocardial infarct size and reduce progression to heart failure after STEMI are needed. Mechanically reducing left ventricular (LV) workload (LV unloading) before coronary reperfusion is emerging as a potential approach to reduce infarct size.
Dr. Jacob Moller, University of Odense Denmark
Total Mechanical Unloading Minimizes Metabolic Demand of Left Ventricle and Dramatically Reduces Infarct Size in Myocardial Infarction
Saku, K., Kakino, T., Arimura, T., Sakamoto, T., Nishikawa, T., Sakamoto, K., Ikeda, M., Kishi, T., Ide, T., Sunagawa, K.
Abstract
BACKGROUND: Left ventricular assist device (LVAD) mechanically unloads the left ventricle (LV). Theoretical analysis indicates that partial LVAD support (p-LVAD), where LV remains ejecting, reduces LV preload while increases afterload resulting from the elevation of total cardiac output and mean aortic pressure, and consequently does not markedly decrease myocardial oxygen consumption (MVO2). In contrast, total LVAD support (t-LVAD), where LV no longer ejects, markedly decreases LV preload volume and afterload pressure, thereby strikingly reduces MVO2. Since an imbalance in oxygen supply and demand is the fundamental pathophysiology of myocardial infarction (MI), we hypothesized that t-LVAD minimizes MVO2 and reduces infarct size in MI. The purpose of this study was to evaluate the differential impact of the support level of LVAD on MVO2 and infarct size in a canine model of ischemia-reperfusion. METHODS: In 5 normal mongrel dogs, we examined the impact of LVAD on MVO2 at 3 support levels: Control (no LVAD support), p-LVAD and t-LVAD. In another 16 dogs, ischemia was induced by occluding major branches of the left anterior descending coronary artery (90 min) followed by reperfusion (300 min). We activated LVAD from the beginning of ischemia until 300 min of reperfusion, and compared the infarct size among 3 different levels of LVAD support. RESULTS: t-LVAD markedly reduced MVO2 (% reduction against CONTROL: -56 +/- 9%, p<0.01) whereas p-LVAD did less (-21 +/- 14%, p<0.05). t-LVAD markedly reduced infarct size compared to p-LVAD (infarct area/area at risk: CONTROL; 41.8 +/- 6.4, p-LVAD; 29.1 +/- 5.6 and t-LVAD; 5.0 +/- 3.1%, p<0.01). Changes in creatine kinase-MB paralleled those in infarct size. CONCLUSIONS: Total LVAD support that minimizes metabolic demand maximizes the benefit of LVAD in the treatment of acute myocardial infarction.
Avoiding hemodynamic collapse during high-risk percutaneous coronary intervention: Advanced hemodynamics of impella support
Verma, S., Burkhoff, D., O’Neill, W. W.
Abstract
The rate of performing primary percutaneous coronary intervention in patients with complex coronary artery disease is increasing. The use of percutaneous mechanical circulatory support devices provides critical periprocedural hemodynamic support. Mechanical support has increased the safety and efficacy of interventional procedures in this high-risk patient population. Predicting patient response to the selected intervention can be clinically challenging. Here we demonstrate a case where complete hemodynamic collapse during PCI was avoided by mechanical support provided by the Impella device. Further, we employ a comprehensive cardiovascular model to predict ventricular function and patient hemodynamics in response to the procedure. New computational tools may help interventionists visualize, understand, and predict the multifaceted hemodynamic aspects of these high risk procedures in individual patients.
Mechanically unloading the left ventricle before coronary reperfusion reduces left ventricular wall stress and myocardial infarct size
Kapur, N. K., Paruchuri, V., Urbano-Morales, J. A., Mackey, E. E., Daly, G. H., Qiao, X., Pandian, N., Perides, G., Karas, R. H.
Abstract
BACKGROUND: Ischemia/reperfusion injury worsens infarct size, a major determinant of morbidity and mortality after acute myocardial infarction (MI). We tested the hypothesis that reducing left ventricular wall stress with a percutaneous left atrial-to-femoral artery centrifugal bypass system while delaying coronary reperfusion limits myocardial injury in a model of acute MI. METHODS AND RESULTS: MI was induced by balloon occlusion of the left anterior descending artery in adult male swine. In the MI group (n=4), 120 minutes of left anterior descending artery occlusion was followed by 120 minutes of reperfusion without mechanical support. In the mechanically supported group (MI+unload; n=4), percutaneous left atrial-to-femoral artery bypass was initiated after 120 minutes of ischemia, and left anterior descending artery occlusion was prolonged for an additional 30 minutes, followed by 120 minutes of reperfusion with device support. All animals were euthanized after reperfusion, and infarct size was quantified by triphenyltetrazolium chloride staining. Compared with baseline, mean left ventricular wall stress and stroke work were not changed at any point in the MI group but were decreased after reperfusion in the MI+unload group (mean left ventricular wall stress, 44 658 versus 22 963 dynes/cm(2); stroke work, 2823 versus 655 mm Hg.mL, MI versus MI+unload). Phosphorylation of reperfusion injury salvage kinase pathway proteins from noninfarcted left ventricular tissue was unchanged in the MI group but was increased in the MI+unload group. Compared with the MI group, total infarct size was reduced in the MI+unload group (49% versus 28%, MI versus MI+unload). CONCLUSIONS: These data support that first unloading the left ventricle despite delaying coronary reperfusion during an acute MI reduces myocardial injury.
Effects of mechanical left ventricular unloading by Impella on left ventricular dynamics in high-risk and primary percutaneous coronary intervention patients
Remmelink, M., Sjauw, K. D., Henriques, J. P., de Winter, R. J., Vis, M. M., Koch, K. T., Paulus, W. J., de Mol, B. A., Tijssen, J. G., Piek, J. J., Baan, J., Jr.
Abstract
OBJECTIVES: We studied online left ventricular (LV) dynamic effects of mechanical LV unloading directly after percutaneous coronary intervention (PCI). BACKGROUND: Limited clinical information is available on the direct LV dynamic consequences of LV unloading in patients undergoing high-risk PCI and primary PCI for acute ST-elevation myocardial infarction. METHODS: The effects of the Impella LP2.5 device on LV dynamics were studied in 11 patients (elective high-risk PCI, n = 6; primary PCI, n = 5). LV pressure and volume were continuously assessed by a pressure-conductance catheter at 4 different support levels of the Impella, from 0 L/min at baseline to 2.5 L/min at maximal support. RESULTS: The response to increased LV unloading was not different between both groups of patients. The pooled data showed no change on global and systolic LV function during increased LV unloading, while diastolic function showed improvement as indicated by an increased LV compliance in all patients. There was a decrease in end-diastolic pressure from 22 +/- 12 to 13 +/- 9 mm Hg (P = 0.0001), in end-diastolic elastance from 0.134 +/- 0.060 to 0.091 +/- 0.064 mm Hg/mL (P = 0.009), and in end-diastolic wall stress from 84 +/- 50 to 47 +/- 39 mm Hg (P = 0.004). CONCLUSIONS: LV unloading decreases end-diastolic wall stress and improves diastolic compliance dose-dependently. Our results indicate beneficial LV unloading effects of Impella during high-risk and primary PCI.
3-D MRI assessment of regional left ventricular systolic wall stress in patients with reperfused MI
Delepine, S., Furber, A. P., Beygui, F., Prunier, F., Balzer, P., Le Jeune, J. J., Geslin, P.
Abstract
The goal of this study was to assess the regional variations of end-systolic wall stress in patients with reperfused Q wave acute myocardial infarction (AMI), with the use of a three-dimensional (3-D) approach. Fifteen normal volunteers and fifty patients with reperfused AMI underwent cardiac MRI that used a short-axis fast-gradient-echo sequence. The end-systolic wall stress was calculated with the use of the Grossman formula with the radius and the wall thickness defined with a 3-D approach using the tridimensional curvature. The mean wall stress was significantly increased at each level of the short-axis plane only in patients with anterior AMI. When calculated at a regional level in patients with anterior AMI, wall stress significantly increased in anterior sector as well as normal sector. In patients with inferior AMI, wall stress significantly increased only in inferior and lateral sectors. In conclusion, the quantification of regional wall stress by cardiac MRI is better with the 3D approach than other methods for precise evaluation in patients with AMI. Despite early reperfusion, the wall stress remained high in patients with anterior AMI.
Left ventricular wall stress as a direct correlate of cardiomyocyte apoptosis in patients with severe dilated cardiomyopathy
Di Napoli, P., Taccardi, A. A., Grilli, A., Felaco, M., Balbone, A., Angelucci, D., Gallina, S., Calafiore, A. M., De Caterina, R., Barsotti, A.
Abstract
BACKGROUND: Apoptosis has been implicated as a possible mechanism in the development of heart failure (HF), but the mechanisms involved remain unclear. In patients with severe dilated cardiomyopathy, we evaluated cardiomyocyte apoptosis in relation to the transmural distribution of Bax and Bcl-2 proteins (2 molecules inhibiting or promoting apoptosis, respectively) and left ventricular wall stresses. METHODS: We studied the presence and distribution of cardiomyocyte apoptosis in 90 tissue samples obtained from 8 patients who were undergoing left ventricular reduction with the Batista (ventricular remodeling) operation. Apoptosis was assessed in tissue samples taken from the entire left ventricular thickness (subdivided in subepicardial, midmyocardial, and subendocardial sections) with the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling (TUNEL) technique and DNA agarose gel electrophoresis. The expression of Bcl-2 and Bax proteins were determined with both Western analysis and immunohistochemistry. RESULTS: TUNEL-positive cells (apoptotic index) were 2.3% +/- 1.4%. Apoptotic cells were predominantly distributed in the subendocardium, where higher levels of Bax protein were detected. The ratio of Bax to Bcl-2 proteins (Bax/Bcl-2) was similar in the midmyocardium or subepicardium, but increased in the subendocardium, where it was directly related to systolic wall stress (y = 0.009x – 0.629; r2 = 0.85, P <.001). The apoptotic index was also directly related to systolic and end-diastolic stresses calculated from hemodynamic and echocardiographic data (r2 = 0.77, P <.001 and r2 = 0.40, P <.01, respectively). CONCLUSIONS: In patients with dilated cardiomyopathy, in whom cardiomyocyte apoptosis is an important cause of cell loss, apoptosis is more extensively localized in the subendocardium and strictly related to ventricular wall stresses and the Bax/Bcl-2 ratio.
JACC, 2018: Journal of the American College of Cardiology
Declining In-Hospital Mortality and Increasing Heart Failure Incidence in Elderly Patients With First Myocardial Infarction
Ezekowitz, J. A., Kaul, P., Bakal, J. A., Armstrong, P. W., Welsh, R. C., McAlister, F. A.
Abstract
OBJECTIVES: The purpose of this study was to examine the long-term incidence of heart failure (HF) in elderly patients with myocardial infarction (MI). BACKGROUND: In-hospital HF is common after MI and is associated with poor short-term prognosis. Limited data exist concerning the long-term incidence or prognosis of HF after MI, particularly in the era of coronary revascularization. METHODS: A population-based cohort of 7,733 patients > or = 65 years of age hospitalized for a first MI (International Classification of Diseases-9th Revision-Clinical Modification code 410.x) and without a prior history of HF was established between 1994 and 2000 in Alberta, Canada, and followed up for 5 years. RESULTS: During the index MI hospitalization, 2,831 (37%) MI patients were diagnosed with new HF and 1,024 (13%) died. Among hospital survivors who did not have HF during their index hospitalization (n = 4,291), an additional 3,040 patients (71%) developed HF by 5 years, 64% of which occurred in the first year. In total, 5,871 (76%) elderly patients who survived their first MI developed HF over 5 years. Among those who survived the index hospitalization, the 5-year mortality rate was 39.1% for those with HF during the index MI hospitalization compared with 26.7% among those without HF (p < 0.0001) during the index MI hospitalization. Over the study period, the 5-year mortality rate after MI decreased by 28%, whereas the 5-year rate of HF increased by 25%. CONCLUSIONS: In this large cohort of elderly patients without a history of HF, HF developed in three-quarters in the 5 years after their first MI; this proportion increased over time as peri-MI mortality rates declined. New-onset HF significantly increases the mortality risk among these patients.
Dr. Joseph Hill, MD, PhD “Heart Failure: The Path Ahead”
Mechanical Pre-Conditioning With Acute Circulatory Support Before Reperfusion Limits Infarct Size in Acute Myocardial Infarction
Navin K. Kapur, Xiaoying Qiao, Vikram Paruchuri, Kevin J. Morine, Wajih Syed, Sam Dow, Nimish Shah, Natesa Pandian, Richard H. Karas.
Abstract
Objectives
This study tested the hypothesis that first reducing myocardial work by unloading the left ventricle (LV) with a novel intracorporeal axial flow catheter while delaying coronary reperfusion activates a myocardial protection program and reduces infarct size.
Background
Ischemic heart disease is a major cause of morbidity and mortality worldwide. Primary myocardial reperfusion remains the gold standard for the treatment of an acute myocardial infarction (AMI); however, ischemia–reperfusion injury contributes to residual myocardial damage and subsequent heart failure. Stromal cell-derived factor (SDF)-1α is a chemokine that activates cardioprotective signaling via Akt, extracellular regulated kinase, and glycogen synthase kinase-3β.
Methods
AMI was induced by occlusion of the left anterior descending artery (LAD) via angioplasty for 90 min in 50-kg male Yorkshire swine (n = 5/group). In the primary reperfusion (1° Reperfusion) group, the LAD was reperfused for 120 min. In the primary unloading (1° Unloading) group, after 90 min of ischemia the axial flow pump was activated and the LAD left occluded for an additional 60 min, followed by 120 min of reperfusion. Myocardial infarct size and kinase activity were quantified.
Results
Compared with 1° Reperfusion, 1° Unloading reduced LV wall stress and increased myocardial levels of SDF-1α, CXCR4, and phosphorylated Akt, extracellular regulated kinase, and glycogen synthase kinase-3β in the infarct zone. 1° Unloading increased antiapoptotic signaling and reduced myocardial infarct size by 43% compared with 1° Reperfusion (73 ± 13% vs. 42 ± 8%; p = 0.005). Myocardial levels of SDF-1 correlated inversely with infarct size (R = 0.89; p < 0.01).
Conclusions
Compared with the contemporary strategy of primary reperfusion, mechanically conditioning the myocardium using a novel axial flow catheter while delaying coronary reperfusion decreases LV wall stress and activates a myocardial protection program that up-regulates SDF-1α/CXCR4 expression, increases cardioprotective signaling, reduces apoptosis, and limits myocardial damage in AMI.
Key Words
myocardial infarction; reperfusion injury; ventricular assist devices
International Cardiology Review on A-CURE 2016
Dr. Valentin Fuster MD, PhD speaks at The 2017 A-CURE Symposium
Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With VA-ECMO
Left Ventricular Assist Devices for Acute Myocardial Infarct Size Reduction: Meta-analysis
Percutaneous cardiac support during myocardial infarction drastically reduces mortality: perspectives from a swine model
Maria Giovanna Trivella, Alessandra Piersgilli, Fabio Bernini, Gualtiero Pelosi, Silvia Burchielli, Stefano Puzzuoli, Claudia Kusmic, Antonio L’Abbate
Abstract
Background/aims
Acute myocardial infarction (AMI) with cardiogenic shock (CS) remains the leading cause of in-hospital death in acute coronary syndromes. In the AMI-CS pig model we tested the efficacy of temporary percutaneous cardiorespiratory assist device (PCRA) in rescuing the failing heart and reducing early mortality.
Methods
In open-chest pigs we induced AMI by proximal left anterior descending coronary artery (LAD) ligation. Eight animals without PCRA (C group) were compared with 12 animals otherwise treated with PCRA (T group), starting approximately at 60 minutes post-occlusion and lasting 120-180 minutes. In 3 animals of the T group, regional myocardial oxygen content was also imaged by two-dimensional near infrared spectroscopy (2D-NIRS) with and without PCRA, before and after LAD reperfusion.
Results
All animals without PCRA died despite unrelenting resuscitation maneuvers (120 minutes average survival time). Conversely, animals treated with PCRA showed a reduction in life-threatening arrhythmia and maintenance of aortic pressure, allowing interruption of PCRA in all cases early in the experiments, with sound hemodynamics at the end of the observation period. During LAD occlusion, NIRS showed severe de-oxygenation of the LAD territory that improved with PCRA. After PCRA suspension and LAD reperfusion, the residual de-oxygenated area proved to be smaller than the initial risk area.
Conclusions
In AMI, PCRA initiated during advanced CS drastically reduced early mortality from 100% to 0% in a 4-5 hour observation period. PCRA promoted oxygenation of the ischemic area during LAD occlusion. Results support the use of PCRA as first line of treatment in AMI-CS, improving myocardial rescue and short-term survival.
Dr. Patrick Hunziker, University Hospital Basel, Switzerland
Dr. Patrick Hunziker speaking on cardiac unloading and recovery in cardiogenic shock
Mark Anderson, MD, Einstein Healthcare Network
Dr. Takahiro Arimura, Kyushu University
Ryan Tedford, MD, Johns Hopkins School of Medicine
Derek Hausenloy, MD, PhD, Duke National University Singapore Reducing Myocardial Infarct Size: Translational Challenges and Opportunities
Trends in mechanical circulatory support use and hospital mortality among patients with acute myocardial infarction and non-infarction related cardiogenic shock in the United States
Innovation Lecture: Navin Kapur, MD | Tufts Medical Center
Nicolas Brozzi, MD | Cleveland Clinic Florida
Kay Everett, MD, PhD | Tufts Medical Center
Ed Soltesz, MD | Cleveland Clinic
Keynote Lecture: Clyde Yancy, MD | Northwestern University
Young Investigator Award: Renata Mazurek, MD | Mt. Sinai
Dr. Howard Chen, Tufts University Medical Center
Dr. Nanna Udesen, Odense University Hospital
ESC, 2018 Mechanical circulatory support as bridge to urgent structural intervention
Patrick Horn, Malte Kelm, and Ralf Westenfeld
Abstract
A 79-year-old woman was admitted in the emergency department as late comer in cardiogenic shock due to subacute nonST-elevation myocardial infarction, which clinically occurred 8 days prior. Coronary angiography depicted occlusion of a small circumflex artery. Revascularization was deemed unreasonable in the light of normal CK and elevated LDH/troponin serum levels. The patient was haemodynamically compromised with elevated lactate and imminent renal and liver failure. Acute Physiology and Chronic Health Evaluation (APACHE II) Score was 25 points corresponding to an in-hospital mortality of 51%. Percutaneous mechanical circulatory support (Impella CP) was implanted and haemodynamics stabilized over 48 h along with
Andreas Schäfer, MD | Hannover Medical Center
Dr. Heimo Ehmke, Univeristy Center Hamburg-Eppendorf
Carsten Tschöpe, MD | Charité – Universitätsmedizin Berlin
Feasibility of Early Mechanical Support During Mechanical Reperfusion of Acute Myocardial Infarct Cardiogenic Shock
O’Neill, W., Basir, M., Dixon, S., Patel, K., Schreiber, T., Almany, S.
Abstract
Although only preliminary, initial experience suggests that rapid door-to-support times are feasible. This approach results in the rapid reversal of the shock state in most patients, allowing operators to obtain TIMI flow grade III rates comparable to those in patients with non-shock ST-segment elevation MI and may improve survival. Given these encouraging pilot data, a large formal quality initiative entitled the Detroit Cardiogenic Shock Initiative has been launched.
Hemodynamic Support With a Microaxial Percutaneous Left Ventricular Assist Device (Impella) Protects Against Acute Kidney Injury in Patients Undergoing High-Risk Percutaneous Coronary Intervention
Flaherty, M. P., Pant, S., Patel, S. V., Kilgore, T., Dassanayaka, S., Loughran, J. H., Rawasia, W., Dawn, B., Cheng, A., Bartoli, C. R.
Abstract
RATIONALE:
Acute kidney injury (AKI) is common during high-risk percutaneous coronary intervention (PCI), particularly in those with severely reduced left ventricular ejection fraction. The impact of partial hemodynamic support with a microaxial percutaneous left ventricular assist device (pLVAD) on renal function after high-risk PCI remains unknown.
OBJECTIVE:
We tested the hypothesis that partial hemodynamic support with the Impella 2.5 microaxial pLVAD during high-risk PCI protected against AKI.
METHODS AND RESULTS:
In this retrospective, single-center study, we analyzed data from 230 patients (115 consecutive pLVAD-supported and 115 unsupported matched-controls) undergoing high-risk PCI with ejection fraction ≤35%. The primary outcome was incidence of in-hospital AKI according to AKI network criteria. Logistic regression analysis determined the predictors of AKI. Overall, 5.2% (6) of pLVAD-supported patients versus 27.8% (32) of unsupported control patients developed AKI (P<0.001). Similarly, 0.9% (1) versus 6.1% (7) required postprocedural hemodialysis (P<0.05). Microaxial pLVAD support during high-risk PCI was independently associated with a significant reduction in AKI (adjusted odds ratio, 0.13; 95% confidence intervals, 0.09-0.31; P<0.001). Despite preexisting CKD or a lower ejection fraction, pLVAD support protection against AKI persisted (adjusted odds ratio, 0.63; 95% confidence intervals, 0.25-0.83; P=0.04 and adjusted odds ratio, 0.16; 95% confidence intervals, 0.12-0.28; P<0.001, respectively).
CONCLUSIONS:
Impella 2.5 (pLVAD) support protected against AKI during high-risk PCI. This renal protective effect persisted despite the presence of underlying CKD and decreasing ejection fraction.
Eugene Braunwald, MD, Harvard University
Improved Regional Myocardial Blood Flow, Left Ventricular Unloading, and Infarct Salvage Using an Axial-Flow, Transvalvular Left Ventricular Assist Device
Richard W. Smalling, David B. Cassidy, Robert Barrett,Bruce Lachterman, Patty Felli, James Amirian
Abstract
The concept of salvage of ischemic myocardial tissue by reperfusion therapy has been suggested by animal1 and human2 studies. Some investigators have reported that the level of collateral flow to the bed at risk determines ultimate infarct size3 others have suggested that the amount of collateral flow and degree of functional recovery are not correlated.4
An additional possible benefit of reperfusion therapy is the concept that late reperfusion may not salvage left ventricular (LV) tissue or function but may limit infarct expansion.5 Additionally, reperfusion may induce further myocardial damage; however, there is no clear consensus regarding the extent or possible modification of this problem.6 Recent interest has focused on the actions of free radicals and use of free radical scavengers at the time of reperfusion. Unfortunately, at the present time, these studies have yielded conflicting results possibly because of differences in models and agents used.7,8
The Current Use of Impella 2.5 in Acute Myocardial Infarction Complicated by Cardiogenic Shock: Results from the USpella Registry
WILLIAM W. O ’NEILL, THEODORE SCHREIBER, DAVID H. W. WOHNS, CHARANJIT RIHAL, SRIHARI S. NAIDU, ANDREW B. CIVITELLO, SIMON R. DIXON, JOSEPH M. MASSARO, BRIJESHWAR MAINI, E. MAGNUS OHMAN
Abstract
Prompt revascularization with percutaneous coronary intervention (PCI) has significantly reduced the incidence of cardiogenic shock (CS) and improved survival in the setting of acute myocardial infarction (AMI).1,2 However, when it occurs, CS remains a highly fatal complication following an AMI,3 despite aggressive revascularization and other adjunctive therapies.3,4 Percutaneous ventricular assist devices (pVADs) have been shown to provide superior hemodynamic support compared to intraaortic balloon pump (IABP) counterpulsation.4,5 In light of the recently reported studies that have failed to show a hemodynamicorsurvivalbenefitofIABPinthesetting ofpost‐AMICS,6–10physiciansmightadoptareflexive strategytousepVADsinthissettingmoreoften.While prospective randomized and adequately powered clinicaltrialsremainwarrantedtoevaluatethepotential benefits of these new devices, real‐world observational data can be useful to provide clinical insights on their use in daily routine practice. In the present study, we sought to evaluate the current use of Impella 2.5 in patients with confirmed CS complicating an AMI undergoing PCI. In particular, we were interested in evaluating the outcomes of patients who received hemodynamic support with Impella 2.5 (Abiomed, Inc., Danvers, MA, USA), prior to PCI versus those who received Impella 2.5 after PCI.
Left Ventricular Support by Catheter-Mounted Axial Flow Pump Reduces Infarct Size
Bart Meyns, Jarek Stolinski, Veerle Leunens, Erik Verbeken, Willem Flameng
Abstract
The transvalvular assist device Impella (Aachen, Germany) is a potent, miniaturized pump that offers the possibility of unloading the left ventricle (LV) via the femoral placement (1). In vivo and clinical use of this device has indicated that the pump produces a mean flow of 4.2 l/min at maximal rotational speed (2). Mechanical unloading of the myocardium during ischemiaandreperfusionhasbeenshowntoreduceLVpressure work and myocardial oxygen consumption (3–5). However, the installation of a left heart bypass during myocardial infarction (MI) is a cumbersome clinical procedure, with important comorbidity. Pharmacologic approaches, such as the early use of beta-blockers,nitroglycerin,andangiotensin-convertingenzyme inhibitors, have achieved infarct size reduction in experimental models (6–10). The use of beta-blockers and angiotensin-converting enzyme inhibitors has rapidly advanced from experimental studies to the clinical recommendation as standard therapy in most patients experiencing an MI. However, clinical trials on the early use (first day of
infarction) showed an increased incidence of hypotension (9–12). Mechanical support combines the beneficial effects of myocardial unloading and an increase in perfusion pressure. It can therefore be used early, even during ischemia and in myocardial failure. This new pump allows unloading of the LV via a peripheral approach in the setting of acute MI. We wanted to investigate the effect of this microaxial blood pump on MI size.
Adjunctive Left Venticular Unloading During Myocardial Reperfusion Plays a Major Role in Minimizing Myocardial Infarct Size
Laschinger JC, Grossi EA, Cunningham JN Jr, Krieger KH, Baumann FG, Colvin SB, Spencer FC.
Abstract
Although prompt institution of reperfusion following coronary artery occlusion has been shown to limit myocardial infarct size, significant “reperfusion injury” may result. We investigated in a canine model whether maintenance of the left ventricle in an unloaded state during the initial reperfusion period following acute myocardial ischemia would result in greater limitation of infarct size or modify the development of reperfusion injury. Group I (control, n = 6) underwent 6 hours of occlusion of the left anterior descending coronary artery without further intervention. In both Group II (n = 6) and Group III (n = 6), the snare was released after 2 hours and hearts were reperfused for 4 hours. In Group III only, the left ventricle was maintained in an unloaded state throughout the entire reperfusion interval via pulsatile left atrial-femoral artery bypass. The results showed that reperfusion of the left ventricle in an unloaded state resulted in significantly improved limitation of both infarct size (area of infarct/area at risk = 16.6% for Group III versus 72.0% for Group I and 55.4% for Group II, p less than 0.001) and area of microvascular damage (area of microvascular damage/area at risk = 4.8% for Group III versus 30.6% for Group II, p less than 0.001). These results indicate that although myocardial reperfusion of the type provided by thrombolysis and/or angioplasty techniques does result in limitation of infarct size when compared to no reperfusion, this limitation is not optimal unless the left ventricle is unloaded during the initial reperfusion period.
Abiomed Receives FDA IDE Approval for Initiation of Door to Unloading (DTU) Prospective Feasibility Study
Abstract
DANVERS, Mass., Oct. 27, 2016 (GLOBE NEWSWIRE) — Abiomed, Inc. (NASDAQ:ABMD), a leading provider of breakthrough heart support and recovery technologies, announced today the U.S. Food and Drug Administration (FDA) approval of a prospective feasibility study to evaluate the use of the Impella CP heart pump for unloading of the left ventricle prior to primary percutaneous coronary intervention (PCI) in patients presenting with ST segment elevation myocardial infarction (STEMI), without cardiogenic shock. This trial will focus on feasibility and safety, and lay the groundwork for a future trial, designed to measure the impact that unloading may have on infarct size related to reperfusion injury, an acceleration of myocardial damage at the time of revascularization, in STEMI patients.
Impella® heart pumps are not currently approved for use in STEMI patients without cardiogenic shock. The STEMI patient segment is contributing to the growing heart failure population and represents a potential new patient indication that may benefit from Impella pump unloading the left ventricle.
STEMI is a type of heart attack caused by a blockage in one of the main heart arteries, preventing the flow of oxygen to the heart. It is estimated that 965,000 people a year have heart attacks 1 , of which approximately 200,000 are classified as STEMI2. The current standard of care is called Door to Balloon “DTB”, for the angioplasty balloon. The recommended treatment in guidelines for STEMI is revascularization (opening the blocked artery) to restore oxygen supply to the heart muscle through primary PCI within 90 minutes or less from the time of first medical contact. Despite current guidelines, 76% of patients experiencing their first acute myocardial infarction (AMI), will develop heart failure within five years 3 . Additionally, within five years of a patient surviving their first heart attack, 36% of men and 47% of women will die due to heart failure1. It is estimated that the number of heart failure patients will grow to 8 million people by 2030 with enormous associated costs 4 . Survival from heart attacks has been improved by the successful DTB protocol; however, this treatment is speculated to be contributing to the growing epidemic of heart failure.
Improving left ventricular unloading following prolonged cardiac arrest using a minimally invasive left ventricular assist device: a prospective animal study in pigs
Andreas Ebeling, Richard Zayat, Michael Fries, Mattias Derwall
Abstract
Cardiopulmonary resuscitation (CPR) is an emergency procedure deployed when a patient suffers cardiac arrest (CA). Compared to conventional CPR, improved survival is observed after CA when CPR is conducted in the presence of a minimally invasive left ventricular assist device, Impella 2.5 (iCPR). However, data on myocardial function during and following iCPR are lacking. To assess cardiac functional parameters during and following iCPR. Five 55.2±2.4 kg pigs were anesthetized, intubated, and implanted with an Impella 2.5. Ventricular fibrillation (VF) was electrically induced and left untreated for 9 minutes before defibrillation was attempted following six minutes of iCPR. During iCPR, the Impella device was set to the maximally achievable flow. 1hr following return of spontaneous circulation (ROSC), mild therapeutic hypothermia was induced for 16 h using a total of 4 liters of 6° C cold saline infusions and ice bags. To assess myocardial recovery, we used 2-D echocardiography, tissue Doppler (TDI), and Speckle-tracking. All animals received transesophageal echocardiography at baseline, during untreated cardiac arrest, at the initiation of iCPR, 30 minutes, and 5 hours following ROSC. Left ventricular (LV) systolic parameters returned to baseline values 5 h after ROSC (global longitudinal strain: -25±4.3% vs. -20±2.7%; p=0.388; EF(%): 64±8.8 vs. 61.32±10.3, p=0.971; stroke volume index (mL/m2): 28.32±8.9 vs. 24.71±12.86, p=0.545). LV volume unloading was also observed over the same time period. LV end-diastolic volume was 55.38±2.8 mL at baseline, peaked after CA at 64.7±9.9 mL, fell to 45.69±7.4 mL 30 min after initiation of iPCR, and was maintained at 49.46±13.9 mL 5 h after ROSC. Recovery of the RV systolic parameters was not observed during the first 5 h following ROSC (baseline vs. 5hr after ROSC: TDI derived TASV (cm/s): 11.6±1 vs. 8.5±1, p=0.005, RV- FAC (%): 42±6.2 vs. 33±6.9, p=0.006). iCPR is able to achieve a full recovery of LV systolic parameters and provides sufficient LV volume unloading. The observed RV distension is likely attributable to extensive volume loading. Further studies are needed to analyze long term LV and RV function following CA and iCPR support
Kenji Sunagawa, MD, PhD, Kyushu University
James Udelson, MD, Tufts Univeristy Medical Center
William O’Neill, MD, Henry Ford Health System
Navin Kapur, MD, Tufts University Medical Center
Understanding the Pressure-Volume Loop
FDA approves the Door To Unloading clinical study investigating the feasibility of primary ventricular unloading in the clinical setting
Dr. Daniel Burkhoff, MD, PhD Columbia University
The Science Behind Acute Ventricular and Myocardial Unloading
Dr. Dan Burkhoff speaking on the science behind acute ventricular unloading and myocardial recovery at the 2016
A-CURE Symposium.
Relationship Between Therapeutic Effects on Infarct Size in Acute MI and One-year Outcomes: Patient-Level Analysis of Randomized Clinical Trials
James Udelson, Harry P. Selker, Robin Ruthazer, Holger Thiele, Manesh R Patel, E. Magnus Ohman, Akiko Maehara, Paul L. Jenkins, Melissa Nichols, Ori Ben-Yehuda, Gregg W. Stone
Abstract
Infarct size (IS) after MI is related to long-term outcomes. Whether a change in IS from an intervention is related to the intervention’s effect on outcomes is unknown. A therapy-induced change in IS is related in direction and/or magnitude to the outcome effect of that therapy. We combined patient-level data from 10 randomized clinical trials of therapies for STEMI. IS was assessed by sestamibi imaging or cardiac MR with analysis in core labs. Each patient within a trial was assigned a variable to represent a treatment’s mean effect on IS. Cox proportional hazards models estimated the association of treatment-related IS to one-year adjudicated clinical outcomes of hospitalization for HF and all-cause mortality. The 10 trials included 2,458 patients, 24% women. IS was measured at median 5 days post-MI. Mean trial IS in the control groups in the 10 trials ranged from 12% – 35% of the LV, and from 12% – 40% among treatment groups. There was a significant relation of treatment effect on IS to treatment effect on one-year HF hospitalization (HR 0.83, 95% CI 0.75 to 0.93, p<0.001). There was no significant relation between treatment effect on IS to treatment effect on one-year mortality (HR 1.04, 95% CI 0.94 to 1.15). The relation to HF hospitalization was stable in sensitivity analyses adjusting for time from MI to IS assessment, and for considering HF as the main outcome and death as a competing risk. This patient-level analysis of randomized placebo-controlled trials of multiple therapeutics for STEMI suggests that a treatment-induced effect on IS is related in direction and quantifiable magnitude to a treatment effect on HF hospitalizations. The data enable the consideration of incorporating infarct size assessment into novel trial analytic approaches as a surrogate endpoint to assess new therapeutics.
LV Unloading using an Impella CP Reduces Wall Stress and Improves Coronary Flow and Perfusion in Infarcted Myocardium
LV Unloading using Impella CP Improves LA Pressure, Function, and Stiffness
Shin Watanabe, Kenneth Fish, Lauren Leonardson, Roger J Hajjar, Kiyotake Ishikawa
Abstract
The impact of pLVAD on LA function and stiffness in HF remains unclear.
Hypothesis: Unloading the LV with an Impella CP improves trans-mitral pressure gradient, leading to a reduction of LA pressure and improved LA function and stiffness. HF is induced by percutaneously occluding the proximal LAD for 90 minutes in Yorkshire pigs (n=4, 40-50 Kg). Two-weeks after the MI, animals underwent LV unloading with an Impella CP for 150 minutes. LA pressure was directly measured by a trans-septal approach and LA volumes were assessed by 3-dimensional echocardiography. LA stiffness was approximated as the slope of minimal and maximal LA pressure–volume coordinates as described previously (Circ Heart Fail. 2015;8:295-303.). Two-weeks after the MI, the animals presented with impaired LVEF (69.7±10.5 to 38.6±7.0 %, P=0.03) and a dilated LV (LV end-systolic volume: 24.55±10.7 to 65.3±16.3 mL, P=0.04) without significant mitral regurgitation. LV unloading with maximal pump support (P8) resulted in an increase in total cardiac output (2.80±0.18 to 3.27±0.22 l/min, P=0.03) and reduced LV end-diastolic pressure (27.5±10.1 to 17.9±4.5 mmHg, P=0.06). These changes were accompanied by a significant reduction in mean LA pressure (17.3±2.6 to 10.8±2.1 mmHg, P=0.001). LA volumes assessed by 3-dimensional echocardiography were also reduced (LA Maximal volume: 40.3±4.6 to 29.0±2.3 ml, P=0.006, LA Minimal volume: 20.3±2.7 to 15.0±2.3 ml, P=0.002). While the total LAEF was not altered from the baseline (49.3±6.4 to 48.5±6.5%, P=0.85), passive LAEF was significantly increased (17.7±1.9 to 39.4±5.6 %, P=0.008), suggesting an improved trans-mitral suction effect. Additionally, LA stiffness assessed by pressure-volume coordinates was improved with Impella support (1.41±0.52 to 0.30±0.16 mmHg/ml, P=0.03). LV unloading using an Impella CP improves passive LA function and reduces mean LA pressure in a recent MI setting. Along with improved LA stiffness, these data implicate a beneficial impact of LV unloading on relieving HF symptoms.
Inhibition of the inflammatory injury following myocardial ischemia-reperfusion in the mouse
Antonio Abbate, Stephano Toldo
Abstract
Reperfusion is effective in reducing ischemic injury in acute myocardial infarction (AMI). Ischemia, however, triggers a secondary injury, known as reperfusion injury, contributing to the overall infarct size. Multiple mechanisms are being explored to favorably modify the effects of reperfusion injury. We hypothesize that inhibition of the Nod-like Receptor Protein-3 (NLRP3) inflammasome limits infarct size following myocardial ischemia/reperfusion (I/R), by inhibiting the inflammatory component of the reperfusion injury. We induced AMI in adult mice by transient ligation of the left anterior descending coronary artery for 30 or 75 minutes. We tested 3 different strategies to inhibit the NLRP3 inflammasome: a newly designed small molecule specifically inhibiting the inflammasome (NLPR3inh), plasma derived alpha-1 antitrypsin (AAT) shown to inhibit the NLRP3 inflammasome, and a synthetic oligopeptide (SP16) designed to reproduce the C-terminal peptide of AAT. Infarct size was measured at 1, 3 and 24 hours and expressed as % of area at risk. Infarct size increased with duration of ischemia from 43±4% with 30 minutes to 65±3% with 75 minutes if ischemia (P<0.001) showing a wavefront of ischemic injury. After 30 minutes of ischemia, however, infarct size progressively increased from 1 to 24 hours after reperfusion (11±2% at 1 hour, 30±5% at 3 hours and 43±4% at 24 hours) showing a wavefront of reperfusion injury. Administration of the NLRP3inh, AAT or SP16 given immediately at reperfusion or within 30 minutes after reperfusion following 30 or 75 minutes of ischemia significantly reduced infarct size at 24 hours (-56%, -44%, -55%, respectively, vs vehicle, all P<0.01). Pharmacological inhibition of the NLRP3 inflammasome within 1 hour of reperfusion limits the secondary inflammatory injury and infarct size following myocardial ischemia-reperfusion in the mouse. Pharmacological interventions alone or in conjunction with other interventions show promise to significantly further improve outcome post myocardial infarction.
To Have Clinical Value, Future Cardioprotective Interventions Must Provide Additive Protection To That From a P2Y12 Receptor Antagonist
Michael Cohen, James M. Downey
Abstract
Patients with AMI are treated with P2Y12 receptor antagonists to suppress platelet aggregation. Although P2Y12 antagonists are used for their anticoagulant effect, our studies reveal that they are also potent postconditioning-mimetics. The latter properties are influencing pre-clinical and clinical searches for adjunctive cardioprotective interventions in unexpected ways. In situ monkey, rabbit, and rat hearts were subjected to ischemia/reperfusion after which hearts were removed, areas at risk determined, and infarct size measured by triphenyltetrazolium chloride staining. Animals were given cangrelor, an intravenous P2Y12 antagonist, starting 10 min before reperfusion to simulate treatment of patients with AMI prior to angioplasty. Infarction was approximately half that seen in untreated animals. This cardioprotection was abrogated by inhibitors of signaling used by postconditioning including wortmannin, LY294002, PD98059, 5-hydroxydecanoate, 8-sulfophenyltheophylline, MRS1754, and 2-mercaptopropionylglycine suggesting that cangrelor protects by a similar mechanism. None restored platelet reactivity indicating that protection was independent of anti-coagulation. Our hypothesis was further strengthened by failure of ischemic pre- or postconditioning to potentiate cangrelor’s cardioprotection. Similar results were seen with clopidogrel and ticagrelor, other P2Y12 antagonists, indicating a class effect. We propose that much of the ability of P2Y12 inhibitors to improve outcomes in AMI can be attributed to direct infarct size reduction from conditioning rather than prevention of stent thrombosis. Because patients treated with P2Y12 antagonists prior to revascularization are already postconditioned, adding another conditioning intervention will be futile. This would explain why recent large trials of ischemic postconditioning or the postconditioning-mimetic cyclosporine in AMI patients were unsuccessful in spite of strong preclinical results. Additional protection in today’s patients will require an intervention not dependent on the conditioning mechanism. Any such intervention must first demonstrate additive protection in animals that have additionally been treated with a P2Y12 antagonist before clinical trials are considered.
LV Unloading using Imepella Reduces LA Pressure and Volume Overload in Chronic Mitral Regurgitation
Kiyotake Ishikawa, Shin Watanabe, Lauren Leonardson, Kenneth Fish, Roger J Hajjar
Abstract
Mitral regurgitation is a common presentation in patients administered due to the decompensated chronic heart failure. Whether an LV-to-aorta pLVAD can be effective in relieving LA overload remains unclear. LV unloading using an Impella CP reduces LA pressure and volume by actively pumping the blood towards forward direction. Chronic heart failure with mitral regurgitation was induced in Yorkshire pigs (n=3, 20 Kg) by percutaneously severing chordae tendinae of the mitral apparatus with a biopsy catheter. Three months later (body weight 43.5 ± 5.0 Kg), the animals underwent LV unloading with an Impella CP with a maximal flow support (p8). Hemodynamics before and during the LV unloading were assessed by Swan-Ganz catheter and pressure volume loop catheter (Millar catheter) in both LA and LV. Additionally, LA volumes were assessed by 3-dimensional echocardiography before and during the Impella support. At 3 months, animals presented with moderate mitral regurgitation (regurgitant fraction 38±10%) with dilated LV (LV end-diastolic volume: 45.5±1.7 mL to 89.7±18.0, P=0.04, LV end-systolic volume: 12.5±1.6 mL to 31.2±10.9, P=0.10, Day0 to 3 month, respectively). LV unloading resulted in a significant reduction of LV end-diastolic pressure (13.6±2.6 to 4.0±4.0 mmHg, P=0.029). Although the visual assessment of MR degree by color-Doppler echocardiography did not change by LV unloading, mean LA pressure decreased significantly (12.3±7.1 to 9.3±6.1 mmHg, P=0.035). LA v-wave, which is accentuated in the mitral regurgitation due to the regurgitant flow, also reduced significantly, indicating a reduction of quantitative MR (17.3±11.2 to 12.3±9.5 mmHg, P=0.038). Furthermore, maximum LA volume assessed by three-dimensional echocardiography was significantly decreased (46.6±13.4 to 29.7±15.9 ml, P=0.043). LV-to-aorta pLVAD can alleviate LA pressure and volume overload in a heart failure due to mitral regurgitation.
Feasibility and Effectiveness of a Multidisciplinary Team Approach in Refractory Cardiogenic Shock Requiring Mechanical Circulatory Support: A Pilot Prospective Study
Byung-Soo Ko, Iosif Taleb, Ryan Larsen, Anwar Tandar, Tae Soo Kang, Stephen McKellar, Josef Stehlik, Greg Stoddard, Antigone Koliopoulou, Edward M. Gilbert, Jose Nativi-Nicolau, James Fang, Craig Selzman, Frederick Welt, Stavros G. Drakos
Abstract
The diversity in both the etiology and the clinical course of refractory cardiogenic shock makes the management of this critical condition challenging. Although a multidisciplinary team based approach has been recommended, it has not been widely adopted. We sought to investigate the feasibility and effectiveness of a multidisciplinary team approach in patients with RCS. A multidisciplinary “SHOCK TEAM”, comprised of a heart failure cardiologist, an interventional cardiologist, an intensivist, and a cardiothoracic surgeon, was established in April 2015 as a part of the Utah Cardiac Recovery-SHOCK program. The program prospectively investigates the management and outcomes of consecutive RCS patients who (i) require temporary percutaneous mechanical circulatory support (MCS) based on predefined criteria and clinical protocol, and (ii) are being managed by the SHOCK TEAM. Nineteen patients who have been enrolled since the launch of the program were compared with the immediately preceding 40 consecutive patients who presented with RCS requiring percutaneous MCS (control group). Baseline characteristics including age (56 vs. 55 in control), comorbidities, presenting hemodynamics, duration of shock before reaching the tertiary care center were comparable between the two groups. We found a marginally significant lower 30-day mortality in the SHOCK TEAM group in a Cox regression model (38.9% vs. 60% in control group; HR, 0.65, p=0.07). ICU stay and hospital stay also tended to be shorter in the SHOCK TEAM group (mean ± SD, 13 ± 13 vs. 27 ± 59 days in control, p=0.33 and 16 ± 15 vs. 31 ± 59 days in control, p=0.30). Furthermore, “Door-to-MCS implementation” time was compared between the groups to evaluate whether the team approach would lead to delays in management, and there was no significant difference. A multidisciplinary shock team approach seems to be feasible, practical, and may improve outcomes of patients with RCS.
Hydrostatic pressure gradient ultrafiltration device: A novel approach for extracellular fluids removal
Yair Feld, Nitai Hanani, Giorgi Shtenberg
Abstract
This study explored the concept of a novel intra peritoneal absorption chamber for fluids removal through the peritoneal membranes. Fluid overload is a common & challenging clinical problem in acutely decompensated heart failure patients (ADHF). Normalization of fluid status in ADHF is associated with improved long term prognosis. Diuretic therapy is limited by kidney function and perfusion pressure, while dialysis and ultrafiltration are associated with significant hemodynamic and electrolyte imbalances when performed in the acute settings. We suggest a novel approach, in which a permeable absorption chamber is implanted in the peritoneum. A negative hydrostatic pressure in the absorption chamber is induced by a pump, prompting fluids ultrafiltration through the peritoneal membranes into the chamber. The accumulated extracellular fluids are drained to an ex vivo collection system or into the urinary system. To examine the feasibility of this concept, we implanted an absorption chamber in the peritoneum of rats and drained fluids through the transplanted chamber. An absorption chamber was prepared from a stainless steel coil with a diameter of 0.4 cm and a length of 3-6 cm covered by a collagen membrane (Permacol, Medtronic). The absorption chamber was implanted in the peritoneum cavity of four Sprague-Dawley rats. Two weeks post implantation the rats were anaesthetized and a peritoneal needle was inserted to the chamber. Extracellular fluid were drained from the chamber at an average rate of 16 ± 6 cc/kg/day during 3 hours of negative hydrostatic pressure induction. The fluids electrolytes and proteins were comparable to the serum content. Implantable absorption chamber enables extracellular fluids removal through the peritoneal membranes. This study suggests that an implantable absorption chamber may be used in fluid-overload clinical conditions, and serve as a possible novel heart failure therapy in acute and potentially chronic settings.
Prognostic relevance of intra-aortic balloon pump in patients with acute myocardial infarction complicated by cardiogenic shock: Nationwide population study in Taiwan
Surenjav Chimed, Batmyagmar Khuyag
Abstract
Intra‐aortic balloon pump (IABP) is the most widely used form of mechanical circulatory support in patients with cardiogenic shock. However, usefulness of IABP in this high risk patient population is conflicting. We examined whether the patient prognosis in Taiwan treated with IABP has improved when IABP was actively used for mechanical circulatory support. We used Taiwan’s National Health Insurance Research Database to retrospectively review 3145 (2358 men [75%]) cardiogenic shock patients who treated primary PCI due to acute myocardial infarction (AMI) between 2000 and 2012. Primary outcome was all cause mortality and secondary outcome was heart failure. A total of 1417 patients who received IABP therapy and 1728 patients who not received non-IABP were selected in this study. The mean age of IABP group and non-IABP group was 68.1±13.1 years and 67±13.3 years, respectively (p=0.02). Median follow-up time for death was 1.51 years in non-IABP group and 1.07 years in IABP group (p<0.0001). Median follow-up time for heart failure was 0.28 years in non-IABP group and 0.09 years in IABP group (p<0.0001). During follow-up period, the adjusted hazard ratio for overall mortality was 1.22 (CI 95% 1.10-1.35, p<0.0001) and for overall heart failure was 1.24 (CI 95% 1.08-1.41, p<0.001). Risk factors for all-cause mortality were previous heart failure, diabetes, chronic kidney disease and hypertension. In this nationwide, population-based, retrospective cohort study, we found that mortality rate and heart failure rate not declined in cardiogenic shock patients who underwent primary PCI plus IABP therapy. Therefore, new type of mechanical circulatory support such as Impella should be considered for high risk, cardiogenic shock patients with AMI.
Association between left ventricular global longitudinal strain and acute pulmonary edema caused by increased left ventricular afterload in patients with STEMI
Surenjav Chimed, Batmyagmar Khuyag, Amarjargal Baldandorj, Lkhagvasuren Zundui, Narantuya Davaakhuu
Abstract
Acute pulmonary edema (APE) is common complication after ST elevation myocardial infarction (STEMI) and often associated with poor prognosis. It is usually caused by decreases of left ventricular contractility and subsequent increase of left ventricular afterload. In this study we aimed to determine association between left ventricular global longitudinal strain (GLS) parameter and APE caused by increased left ventricular afterload. We chose patients with STEMI and who were treated by primary PCI in this study. Two dimensional speckle tracking echocardiography was used to assess left ventricular GLS. Study endpoint was APE caused by increased left ventricular afterload. Univariable and multivariable logistic regression analysis was used to determine association between GLS and APE. A total of 524 patients were enrolled. Mean age was 60 ± 13 years old and majority of patients were male 444 (84.7%). During admission, APE was occurred in 15 (2.9%) patients. Univariable logistic regression analysis showed GLS is significantly associated with APE and every 1 unit change of GLS is associated with 1.34 times increased probability of having APE (OR 1.34, 95% CI 1.17-1.53, p<0.001). After adjustment of clinical, angiographic and conventional echocardiographic indices, left ventricular GLS was independently associated with APE (OR 1.25, 95% CI 1.06-1.46, p<0.01). Predictive capacity of left ventricular GLS was better than LVEF (c-statistic 0.824, 95% CI 0.719-0.929, p<0.001). Speckle tracking derived GLS is strong and independent predictor of APE caused by increased left ventricular afterload in patients with STEMI after primary PCI. Prognostic capacity of GLS is better than LVEF.
A new animal model for investigation of mechanical unloading in hypertrophic and failing hearts: combination of transverse aortic constriction and heterotopic heart transplantation
Andreas Schaefer, Yvonne Schneeberger, Justus Stenzig, Daniel Biermann, Marisa Jelinek, Hermann Reichenspurner, Thomas Eschenhagen, Heimo Ehmke, Alexander P Schwoerer
Abstract
Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC) and heterotopic heart transplantation (hHTx) in rats. To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations. 50 TAC procedures were performed with a survival of 92% (46/50). When compared to healthy rats left ventricular surface decreased to 5.8±1.0 mm² (vs. 9.6± 2.4 mm²) (p= 0.001) after three weeks with a fractional shortening (FS) of 23.7± 4.3% vs. 28.2± 1.5% (p=0.01). Six weeks later, systolic function decreased to 17.1± 3.2% vs. 28.2± 1.5% (p=0.0001) and left ventricular inner surface increased to 19.9±1.1 mm² (p=0.0001). Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46). All transplanted organs survived two weeks of mechanical unloading. Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure.
Potential of Regenerative Therapy with Medical Assist Devices
Timothy Henry
Abstract
Heart failure continues to be the leading cause of morbidity and mortality not only in the United States but throughout the world. Despite advances in medical and device therapy, many patients continue to have significant symptoms leaving heart transplantation, left ventricular assist devices (LVAD), or palliative care as the only options. This has stimulated interest in regenerative therapies including stem cell therapy. Based on positive preclinical results, the initial clinical trials used predominantly autologous bone marrow mononuclear stem cells (BMC). Trials with BMC demonstrated excellent safety but only modest efficacy most likely due to the significant variability with autologous BMC which is related to the decline in the number and potency of stem cells with age and cardiac risk factors. This has stimulated the next generation of cell therapies which include allogeneic cells, cardiac derived cells, and enhanced cultured autologous cells. A recent large double-blind, placebo controlled Phase 2 trial using enhanced BMC cells (IxCell-DCM) demonstrated a significant reduction in mortality and cardiovascular hospitalizations in cell-treated patients. A second large Phase 2 trial using enhanced mesenchymal stem cells (MSCs) will be presented at ESC and a large Phase 3 trial with allogeneic MSCs is underway. An even more attractive idea is to combine the benefits of novel, mechanical left ventricular support devices with regenerative therapy. To date, there have been a total of 67 patients randomized in 11 published clinical trials with the combination of cell therapy and LVAD trials. The largest of these (N=30) was an NIH-sponsored trial using allogeneic MSCs which demonstrated a potential benefit in LVAD weaning and a suggestion of mortality benefit. In summary, despite optimal medical and device therapy the number of patients with advanced HF continues to grow. Both novel mechanical assist devices and regenerative therapy represent potential solutions. The combination of these two unique therapies may be a particularly attractive solution.
Assessment of Impella position on supine chest X-ray in the intensive care unit. Introduction and applicability of the Aortic Valve Location Ratio
Dagmar M. Ouweneel, Krischan D. Sjauw, Esther M.A. Wiegerinck, Alexander Hirsh, Jan Baan Jr, Bas A.J.M. de Mol, Wim K. Lagrand, R. Nils Planken, José P.S. Henriques
Abstract
Maintaining correct Impella position is a key factor for optimal functioning of the Impella device. The aortic valve is an important landmark for correct positioning. It would be of great value if the device position could be determined accurately by plain supine chest X-ray in the intensive care unit. The aim was to develop a ratio-based tool for determination of the aortic valve location on plain supine X-ray which can be used to monitor Impella position in the intensive care unit. Supine anterior-posterior chest X-ray of patients with an aortic valve prosthesis (n=473) were analyzed to determine the location of the aortic valve. We calculated several ratios with the potential to determine the position of the aortic valve. The Aortic Valve Location (AVL) ratio, defined as the distance between the carina and the aortic valve, divided by the thoracic width, was found to be the best performing ratio. The AVL ratio determines the location of the aortic valve caudal to the carina, at a distance of 0.25±0.05 times the thoracic width for male patients and 0.28±0.05 times the thoracic width for female patients. The AVL ratio was validated using computed tomography images of patients with angina pectoris without known valvular disease (n=95). There was a good correlation between the Impella position assessed with the AVL ratio and with echocardiography (n=53). The Aortic Valve Location Ratio enables accurate and reproducible localization of the aortic valve on supine chest X-ray. This tool is easily applicable and can be used for assessment of cardiac device position in patients on the ICU.
Jane Wilcox, MD | Northwestern University
Distinguished Lecture: Emma Birks, MD, PhD | University of Kentucky
Manreet Kanwar, MD | Allegheny Health Network
Best in Research Award: Tharusan Thevathasan, MD | Charité – Universitätsmedizin Berlin
What is acute cardiac unloading?
Daniel Burkhoff, MD, PhD: The Science Behind Acute Ventricular and Myocardial Unloading
James Udelson, MD, speaking on Infarct Size as an endpoint in clinical trials
Hemodynamics of Mechanical Circulatory Support
Daniel Burkhoff, Gabriel Sayer, Darshan Doshi, Nir Uriel
Abstract
An increasing number of devices can provide mechanical circulatory support (MCS) to patients with acute hemodynamic compromise and chronic end-stage heart failure. These devices work by different pumping mechanisms, have various flow capacities,are inserted by different techniques,and have different sites from which blood is with drawn and returned to the body. These factors result in different primary hemodynamic effects and secondary responses of the body. However, these are not generally taken into account when choosing a device for a particular patient or while managing a patient undergoing MCS. In this review, we discuss fundamental principles of cardiac, vascular, and pump mechanics and illustrate how they provide a broad foundation for understanding the complex interactions between the heart, vasculature, and device, and how they may help guide future research to improve patient outcomes. (J Am Coll Cardiol 2015;66:2663–74) © 2015 by the American College of Cardiology Foundation.
Dr. Dan Burkhoff, Columbia University
Journal of Cardiovascular Transnational Research Special Issue: Acute Ventricular Unloading
Dan Burkhoff, MD, PhD, Columbia University Perspective on Acute Unloading
International Cardiology Review on A-CURE 2016
Abstract
This supplement to the International Cardiology Review is devoted to the proceedings of the first annual A-CURE Symposium that was held in Rome, Italy, in August of 2016. The 1-day meeting brought together experts from a number of disciplines – including interventional cardiologists, heart failure specialists, cardiac surgeons, molecular biologists, and biomedical engineers – to discus the science behind and clinical applications of acute cardiac unloading. Over 100 physicians, clinical and pre-clinical researchers, basic researchers, medical students, post-doctoral scientists, and graduate students from 21 different countries were in attendance. The ICR Supplement features a number of the presentations from the Symposium describing the basic science underlying acute cardiac unloading, its clinical applications, and the opportunities in and challenges of performing clinical trials.