Sample Abstracts from the 2016 A-CURE Symposium

andreas-ebeling-page-001

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

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james-udelson-page-001

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.

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kiyotake-ishikawa-page-001

LV Unloading using an Impella CP Reduces Wall Stress and Improves Coronary Flow and Perfusion in Infarcted Myocardium

Kiyotake Ishikawa, Shin Watanabe, Lauren Leonardson, Kenneth Fish, Roger J Hajjar

Abstract

LV unloading may improve coronary perfusion by increasing cardiac output and reducing LV wall stress. Whether sustained LV unloading improves myocardial perfusion in a post-MI setting remains uncertain. Unloading a post-MI LV with an Impella CP increases coronary flow and myocardial perfusion by reducing LV wall stress and increasing cardiac output. To mimic patients who need LV support, large anterior transmural MI was induced by occluding the proximal LAD for 90 minutes in Yorkshire pigs (n=5, 40-50 Kg) followed by a thrombus injection through the balloon lumen to induce total occlusion of the LAD. Two-weeks after the MI, animals underwent LV unloading with an Impella CP for 120 minutes. Epicardial coronary flow was assessed by coronary flow wire before, 5 minutes and 120 minutes after LV unloading. Myocardial perfusion was assessed using fluorescent microspheres before and 120 minutes after LV unloading. Coronary angiograms revealed TIMI 2 flow in 4 animals, and TIMI 3 flow in one animal. LV unloading with maximal pump support (P8) for two hours resulted in an increase in total cardiac output (3.08 to 3.93 l/min, P=0.07). Impella support significantly reduced end-diastolic volume (109±17 to 85±12 mL, P=0.02) and end-diastolic pressure (29.3±5.6 to 19.2±6.9 mmHg) resulting in a significant decrease in LV end-diastolic wall stress (infarct: 34.4±5.5 to 20.2±5.2 kdynes/cm2, P=0.03; remote: 32.4±8.6 to 19.3±6.0 kdynes/cm2, P=0.03). Coronary flow increased acutely (LAD: 6.7±1.8 to 10.2±1.5 cm/s, P=0.03, LCx: 8.4±2.7 to 10.4±3.6 cm/s, P=0.31) and remained elevated at 120 minutes (LAD: 9.8±1.3 cm/s, P=0.058, LCx: 12.4±4.2 cm/s, P=0.058). Compared to baseline, myocardial perfusion as measured by fluorescent microspheres within the infarct zone was significantly increased (87±67%, P=0.02), while perfusion of the remote non-ischemic myocardium was similar compared to the baseline (-2±15%, P=0.89), likely due to auto-regulation in the non-injured myocardium. Sustained LV unloading using an Impella CP increases coronary flow and perfusion of infarcted myocardium for at least 2-hours.

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shin-watanabe-page-001

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.

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toldo-and-abbate-page-001

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.

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michael-cohen-page-001

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.

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shin-watanabe-2-page-001

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.

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yair-feld-page-001

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.

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stavros-drakos-page-001-1

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.

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surenjav-chimed-2-page-001

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.

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surenjav-chimed-1-page-001

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.

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andreas-schaefer-page-001

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.

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tim-henry-page-001

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.

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dagmar-ouweneel-page-001

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.

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