The 2nd Annual Acute Cardiac Unloading and Recovery (A-CURE) Symposium was held in Barcelona, Spain, on August 25, 2017. Over 100 clinical and basic researchers from around the world participated in this year’s conference, which was hosted by the A-CURE Working Group. The mission of the A-CURE Working Group is to advance the science and mechanistic understanding of acute cardiac unloading and to support the translation of basic and clinical research into therapies aimed at heart muscle recovery. The last 20 years has seen major technical advances in mechanical circulatory support and research focused on pharmacological means to unload the heart. This progress has enabled new treatment modalities within the clinic for addressing myocardial infarction, cardiogenic shock, acute decompensated heart failure, and advanced heart failure. The goal of these approaches is to unload the heart of its metabolic demand and mechanical workload. Current research indicates that ventricular unloading has profound effects on both cardiac physiology and the cardioprotective processes associated with recovery after damage to the heart has taken place. Clinical and basic researchers from around the world have recognized the potential applications of this new technology to treat and understand several cardiac pathologies. The A-CURE Symposium is the only scientific conference dedicated to advancing the science and clinical application of acute unloading aimed at heart muscle recovery. The A-CURE initiative is expected to grow as the impact of this progressing science advances further into the clinic. This year’s keynote address by Dr. Valentin Fuster identified the far-reaching impact of myocardial infarction on the development of cardiovascular disease and heart failure. The lectures and abstracts presented during the 2nd annual meeting included basic and translational science and also presented cutting-edge clinical applications of acute unloading. The collection of selected abstracts presented here demonstrates the broad spectrum of research on display at the 2nd Annual A-CURE Symposium.Navin Kapur, MD Bill O'Neill, MD Dan Burkhoff, MD, PhD (Columbia University)Mark Anderson, MD Co-Chairs, A-CURE Working GroupLara Reyelt, Michele Esposito, Xiaoying Qiao, Kevin Morine, Shiva Annamalai, Courtney Boggins, Peter Natov, Hyunji Koo, Richard H Karas, Navin K KapurTufts Medical CenterBackground: Ischemic heart failure is a major cause of morbidity and mortality worldwide. We previously reported that compared to primary reperfusion (PR), first reducing myocardial oxygen demand by activating an acute mechanical circulatory support device while delaying coronary reperfusion primary unloading (PU) reduces myocardial damage in models of acute myocardial infarction (AMI).Hypothesis: The purpose of this study was to explore the long-term outcomes associated with primary unloading before myocardial reperfusion compared to primary reperfusion alone.Methods: Animals were randomized into two groups, the control arm (PR) and the intervention arm (PU). The PR cohort underwent 90 min of left anterior descending (LAD) occlusion followed by 120 min of reperfusion. The PU group underwent 90 min of LAD occlusion, followed by insertion and activation of an Impella CP pump, with an additional 30 min of LAD occlusion, followed by 120 min of reperfusion. Both groups were recovered and monitored for 28 days. After 28 days, animals underwent cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE) to quantify final myocardial infarct size using a Philips Achieva 1.5 Tesla scanner and repeat cardiac catheterization. Animals were then euthanized, and myocardial infarct size was determined using TTC staining.Results: Fourteen animals completed the ischemia-reperfusion phase of the protocol. Two animals in the PR group died within 6 h after reperfusion, and 12 animals survived to 28 days . Compared to PR, LV scar as determined by LGE  and anatomic pathology  was significantly lower after PU . CMR-derived LV volumes, LV ejection fraction, and LV mass were not different between groups. At 28 days, PU significantly increased cardiac output  and LV stroke work  more than PR. Compared with PR, levels of b-MHC, calcineurin, and BNP mRNA were lower; and SERCA mRNA levels were higher within the non-infarct zone after PU. At 28 days after AMI, circulating brain natriuretic peptide levels were lower after PU compared with PR .Conclusions: PU reduces LV scar, improves LV function, and limits indices of maladaptive cardiac remodeling and circulating BNP levels 28 days after AMI. Studies exploring primary unloading as an approach to limit ischemic heart failure are required.Kiyotake Ishikawa, Olympia Bikou, Shin Watanabe, Kenneth Fish, Lauren Leonardson, Roger HajjarMt. Sinai HospitalBackground: The Impella, a left ventricle (LV)-to-aorta percutaneous ventricular assist device, supports systemic hemodynamics and unloads the LV. The impact of Impella support on the left atrium (LA) has not been clearly defined.Hypothesis: LV support using Impella reduces LV end-diastolic pressure (EDP) and consequently reduces LA pressure. This leads to alleviation of LA stretch and inhibits atrial arrhythmias through attenuating stretch-induced oxidative stress.Methods: Yorkshire pigs underwent myocardial infarction (MI) creation (n = 10) using a percutaneous approach. One to 2 weeks after MI, pigs underwent LV unloading using an Impella CP. A pressure-volume catheter was inserted into the LA using a trans-septal approach, and the LA pressure-volume loops were continuously monitored during the experiments. Atrial arrhythmia inducibility was examined by rapidly pacing the right atrium.Results: After MI, pigs presented with reduced LV ejection fraction (EF), increased LVEDP, and increased LA volumes. LV unloading with Impella CP resulted in the reduction of the LVEDP, while mean LA pressure and maximum LA volume decreased proportionally to LVEDP. LA pressure-volume loops exhibited a pump-flow dependent left-downward shift. This was associated with a reduced LA active work and improved LA passive stiffness. Prior to Impella, 80% of the pigs were arrhythmia-inducible. However, only 30% of the pigs were inducible after the Impella LV support. Time to spontaneous termination of atrial arrhythmias was significantly shorter with Impella LV support, and this correlated with LA maximum volume as well as with LA active work. LA molecular analysis revealed that NOX2 expression was increased after MI, whereas Impella LV support reduced NOX2 levels together with the reduction in oxidative stress markers. These results suggest that Impella relieves LA stretch and reduces atrial arrhythmogenicity through inhibition of NOX2-dependent oxidative stress.Conclusions: Impella reduces LA pressure, unloads LA, and reduces atrial arrhythmogenicity in a post-MI pig model.Genya Sunagawa, Keita Saku, Takahiro Arimura, Takuya Akashi, Takuya Kishi, Hiroyuki Tsutsui, Kenji SunagawaKyushu UniversityBackground: Acute myocardial infarction (MI) remains a leading cause of chronic heart failure (CHF). The presence of unsalvaged myocardium leads to cardiac remodeling and CHF. Reducing myocardial oxygen consumption (MVO2) in acute MI is known to reduce infarct size. We reported that the combination of LV mechanical unloading and chronotropic unloading  synergistically reduced MVO2 more than 60%. In this study, we examined if the combination therapy outperforms mechanical unloading alone in reducing MI size and preventing heart failure in the long-term. We used a transvascular LV assist device (Impella) for mechanical unloading and If channel inhibitor ivabradine (IVA) for chronotropic unloading.Methods: In 18 anesthetized dogs, we ligated the coronary arteries for 180 min and then reperfused. We initiated Impella or Impella and IVA  60 min after the onset of ischemia and continued the support until 60 min after reperfusion. We allocated animals into three groups: no treatment , Impella (n = 6), and Impella + IVA (n = 6). Four weeks after MI, we compared LV function, heart failure parameters, and infarct size.Results: All results were reported in the following order: IR, Impella, and Impella + IVA. In the acute phase of MI, heart rate in Impella + IVA was by far lower than other groups . Four weeks after MI, Impella + IVA normalized LV end-systolic elastance  and decreased LV end-diastolic pressure  and NT-proBNP . Impella + IVA strikingly reduced the infarct size more than 70% (≈ 1–4.3/15.6) .Conclusions: Combination of LV mechanical unloading and a bradycardic agent synergistically reduced infarct size and prevented subsequent heart failure. This “mechano-chronotropic unloading” may serve as a powerful option to prevent CHF after MI.Carlos del Rio, S Bennett, J Noel-Morgan, SR Roof, EG Geist, BL Youngblood, E Ferris, Y Ueyama, PI McConnell.Myokardia, Natiowide Children’s HospitalBackground: By design, intra-cardiac left ventricular assist devices (LVADs) support systemic hemodynamics and cardiac output (CO) while decreasing myocardial preload and stroke volume.Hypothesis: Under certain conditions , LVAD-support could lead to paradoxical increases in the effective arterial elastance (Ea), hindering mechano-energetic unloading. This study tested the hypothesis by assessing the acute effects of LVAD-support on systemic hemodynamics, left-ventricular (LV) mechano-energetics, and oxygen consumption (MVO2) in vivo.Methods: Healthy sheep (n = 12) were instrumented to assess MVO2 , systemic arterial pressures/CO, and LV pressure-volume relationships. Data before/after LVAD unloading with a continuous flow device  were compared to those obtained during partial vena cava occlusion ; data were also collected when phenylephrine was administered to restore systemic hemodynamics (CTRL + PE). Heart rate was held constant by atrial pacing. Atrial natriuretic peptide (ANP) production was quantified.Results: Partial LVAD-support (57 ± 4%) decreased LV preload (− 13 ± 2%), filling pressures (− 29 ± 7%), and SV (− 28 ± 5%) and preserved systemic/peak LV pressures (− 3 ± 2%) and CO (− 1 ± 1%). Both the estimated Ea (+ 40 ± 11%) and Ees (+ 33 ± 7%) increased with support. Despite marked reductions in SW (− 29 ± 5%) and PVA (− 31 ± 4%), both coronary flow (− 3 ± 4%) and MVO2 (+ 1 ± 2%) changed negligibly. Complete support (109 ± 9%) decreased LV pressures (− 33 ± 10%), normalizing Ea (− 1 ± 14%) but not Ees (+ 54 ± 12%) with moderate MVO2 reductions (− 13 ± 4%). Unsupported reductions in preload (CTRL) decreased MVO2 (− 39 ± 4%), Qlcx (− 53 ± 4%), and PVA (− 58 ± 4%), while Ea and Ees remained unchanged; pressure support (CTRL + PE) increased Ea and blunted the MVO2 reductions (− 7 ± 2%). LVAD-support altered the MVO2 vs PVA relationship and triggered ANP release.Conclusions: These results suggest that intra-cardiac LVAD-support can trigger mechano-energetic alterations, paradoxically hindering the ability of an LVAD to energetically unload the ventricle. These observations could have important implications in the understanding of myocardial recovery under LVAD-support.Michele Esposito, Xiaoying Qiao, Yali Zhang, Shiva Annamalai, Lara Reyelt, Courtney Boggins, Kevin Morine, Richard H Karas, Navin KapurTufts Medical CenterBackground: Stromal derived factor 1 alpha (SDF1a) is a constitutively expressed cardioprotective chemokine that is rapidly degraded by proteases. We reported that compared to primary reperfusion (PR), first reducing myocardial oxygen demand by activating a trans-valvular pump (Impella CP) while delaying coronary reperfusion (primary unloading [PU]) reduces infarct size in acute myocardial infarction (AMI).Hypothesis: We hypothesize that PU reduces proteolytic degradation of SDF1a thereby increasing SDF1a signaling via the receptor CXCR4 in AMI.Methods: AMI was induced by occlusion of the left anterior descending artery (LAD) for 90 min in male swine (n = 4/group). In the PR group, the LAD was reperfused for 120 min. In the PU group, after 90 min of ischemia, an Impella CP was activated, and the LAD left occluded for an additional 30 min, followed by 120 min of reperfusion. Whole-transcript expression analysis was performed on RNA from the infarct zone using Porcine 1.0 ST microarrays and ConsensusPathDB programs. Quantitative polymerase chain reaction, western blots, and activity assays determined expression and activity of the SDF1a signaling pathway. Sham-operated LV samples served as controls.Results: Compared to PR, PU reduced fibrotic and inflammatory gene expression including reduced transcript levels of matrix-metalloprotease-2 (MMP2), MMP9, and dipeptidyl peptidase-4 (DPP4). Compared to PR, PU increased SDF1a protein levels within the infarct zone. Gel zymography confirmed reduced activity levels of MMP2 and MMP9 within the infarct zone after PU, not PR. Compared to PR, PU attenuated DPP4 protein levels and activity and protein levels of CXCR7, an SDF1a sequestration receptor, within the infarct zone. To explore a functional role for SDF1a in PU, adult male swine received intra-coronary injections of AMD3100, a CXCR4 receptor antagonist, after Impella CP activation. Loss of CXCR4 activity attenuated cardioprotective signaling via Akt, Erk, and GSK3b and increased infarct size compared to vehicle-treated controls.Conclusions: We introduce a novel mechanism by which PU limits proteolytic degradation and CXCR7 mediated sequestration of SDF1a, thereby increasing cardioprotective signaling via SDF1a and overcoming a critical barrier to SDF1a therapeutics in AMI.Keita Saku, Genya Sunagawa, Takahiro Arimura, Takuya Kishi, Hiroyuki Tsutsui, Kenji SunagawaCenter for Disruptive Cardiovascular Medicine, Kyushu UniversityBackground: Although early reperfusion is essential to save lives and prevent subsequent heart failure (HF) in AMI, the door-to-reperfusion time cannot be drastically shortened in the real-world setting. To overcome this limitation, we recently developed intravascular vagal nerve stimulation (iVNS) i.e., neural unloading and demonstrated that iVNS initiated 90 min after the onset of ischemia reduced infarct size by 61% and prevented HF in a dog model of ischemia/reperfusion. However, in the clinical setting, starting iVNS could be much later and introducing iVNS could delay reperfusion. Therefore, we examined the impact of iVNS under a more realistic clinical scenario. We started iVNS very late (180 min after the onset of ischemia), delayed reperfusion by 30 min, and examined its impact 4 weeks later.Methods: In mongrel dogs, we occluded the LAD for 180 min to create ischemia and then reperfused for 60 min . In iVNS (n = 7) 180 min after the LAD occlusion, we applied iVNS for 60 min and delayed the reperfusion by 30 min . We increased the intensity of iVNS to the maximum level where hemodynamics remained stable . Four weeks after AMI, we compared LV function and infarct size between the control group and dogs treated with iVNS.Results: In comparison with control, despite a 30-min delay in reperfusion (longer ischemic period), iVNS increased LV ejection fraction  and end-systolic elastance  and decreased LV end-diastolic pressure . iVNS more than halved the infarct size .Conclusions: iVNS initiated after the 180 min of ischemia prevented the worsening of LV function and markedly reduced infarct size despite delaying reperfusion. Therefore, neural unloading may serve as a therapeutic option in the management of AMI.Jan-Thorben Sieweke, Jörn Tongers, Christian Kühn, L. Christian Napp, Axel Haverich, Johann Bauersachs, Andreas SchäferHannover Medical SchoolBackground: Despite improvements in the management of cardiogenic shock (CS) complicating acute myocardial infarction (AMI), mortality remains unreasonably high. In the IABP-Shock II Trial, intra-aortic balloon counterpulsation did not affect mortality in CS patients. Larger prospective data on hemodynamic support strategies are still lacking.Methods: We investigated 154 consecutive patients with CS between January 2013 and April 2016 who were supported by an Impella for isolated LV support at our department. In order to compare the efficacy of active LV unloading, we focused on patients fulfilling the inclusion/exclusion criteria of the IABP shock II Trial.Results: Out of 154 consecutive patients, 125 were excluded . Compared to the IABP-Shock II Trial, our cohort  exhibited similar baseline characteristics and a similar severity of CS as assessed by SAPS-II score (50.4 ± 1.6). In our registry, coronary disease state was severe with increased prevalence of prior PCI (44.8%), prior coronary artery bypass grafting  and a greater amount of patients with out-of-hospital cardiac arrest (55.2%) with return of spontaneous circulation after 14.2 ± 2.5 min. The safety outcome was reasonable as in-hospital re-infarction or thrombosis did not occur in our cohort. In the IABP Shock II Trial, 30-day mortality was 41.3% in the control group and 39.7% in the IABP group. In our patients, however, early usage of Impella was associated with a mortality rate as low as 20.7%.Conclusions: These findings suggest that the Impella platform is a promising device for mechanical hemodynamic support in CS particularly due to AMI. To be able to interpret these findings more accurately, a propensity score matched analysis is needed. Therefore, we collaborated with the UKE Hamburg to perform a propensity score matched analysis in a larger collection of patients. Our registry data highlight the serious challenge of prospective studies to include enough patients to provide the study with sufficient statistical power. The Dan Shock trial is a promising prospective trial which is now extended into Germany .Ole Møller-Helgestad, Janus Adler Hyldebrandt*, Ann Banke, Charlotte Svejstrup Rud, Nanna Louise Junker Udesen, Louise Linde, Lisette Okkels Jensen, Henrik Schmidt, Hanne Berg Ravn#, Jacob Eifer MøllerOdense UniversityBackground: The use of mechanical circulatory support, including Impella CP and veno-arterial extra corporeal membrane oxygenation (ECMO), is increasing in the treatment of cardiogenic shock (CS) following STEMI. However, studies comparing the technologies are lacking.Hypothesis: A combination of norepinephrine and Impella CP is associated with unloading of the left ventricle (LV) compared to ECMO in a large porcine model of CS.Methods: CS was induced by staged microembolization of the left main coronary artery in 12 female swine. A conductance catheter was placed in the LV for measurement of LV end-diastolic pressure (LVEDP), LV end-diastolic volume (LVEDV), and pressure-volume area (PVA). Arterial lactate levels were obtained at CS and 60 min of mechanical support. Data are presented as medians at CS and as relative percentages of CS at 60 min of support, with 95% confidence intervals. A two-sample Wilcoxon rank-sum test was used to identify differences between Impella CP and ECMO.Results: In Impella CP (n = 6) vs ECMO (n = 6), cardiac output was 2.6 L/min  vs 2.0 L/min  p = 0.2, MAP 31 mmHg  vs 35 mmHg  p = 0.5, lactate 3.9 mmol/L  vs 2.8 mmol/L  p = 0.3, LVEDP 20 mmHg  vs 16 mmHg , p = 0.3, LVEDV 178 mL  vs 160 mL  p = 0.1, and PVA 2827 mmHg*mL  vs 2594 mmHg*mL  p = 0.3. At 60 min of mechanical support with Impella CP vs ECMO, relative changes from CS of LVEDP was 65%  vs 113%  during support. The rate of pneumonia was assessed as a secondary endpoint.Results: The groups (Impella vs IABP) did not differ in terms of age, SOFA score, Apache score, or basal serum lactate levels. Total fluid balance was calculated as positive during support and did not differ in both groups: + 2.4 ± 0.6 l vs + 1.8 ± 0.4 l at day 1 (p = 0.57), + 1.3 ± 0.7 l vs + 0.6 ± 0.4 l at day 2 (p = 0.86) and + 0.2 ± 0.7 l vs +0.3 ± 0.9 l at day 3 (p = 0.80). Pulmonary congestion as indicated with the Halperin score decreased post-implantation in patients with Impella support , but it not decrease in patients with IABP support . The incidence of pneumonia did not differ between Impella group  and IABP group  (p = 0.18).Conclusions: Left ventricular unloading by Impella support reduces pulmonary congestion in patients with cardiogenic shock despite performed positive fluid balance. Therefore, Impella support may facilitate treatment of congestive pneumonia in patients with cardiogenic shock, although prospective trials in larger patient cohorts are required.Daniel Scheiber, Elric Zweck, Tomas Jelenik, Patrick Horn, Udo Boeken, Diyar Saeed, Malte Kelm, Michael Roden, Julia Szendrödi, Ralf WestenfeldHeinrich-Heine University, Düsseldorf, GermanyBackground: Increased ventricular filling pressure and volume overload are hallmarks of advanced heart failure (HF). Previous studies have linked pressure and volume overload with alterations in myocardial substrate utilization and mitochondrial energy production in HF. It is well established that mitochondrial production of reactive oxygen species is increased in HF leading to oxidative stress. Mechanical ventricular unloading has been shown to induce protective reverse remodeling in myocardial tissues; however, little is known about the impact of ventricular unloading on myocardial mitochondrial energy metabolism. In this study, we compare mitochondrial reactive oxygen species (ROS) production and respiration in human hearts that were mechanically supported prior to explantation for heart transplantation (HTX) to unsupported hearts.Hypothesis: We hypothesize that (1) chronic left ventricular unloading reduces myocardial mitochondrial ROS production, and (2) improves myocardial mitochondrial oxidative capacity in patients suffering from advanced HF.Methods: We prospectively evaluated 11 patients undergoing HTX between October 2016 and May 2017 in this single-center trial. Myocardial tissue specimens were harvested from macroscopically scar-free areas of the left ventricle during heart explantation. Mitochondrial hydrogen peroxide emission was analyzed fluoroscopically in an Oxygraph-2k . Mitochondrial oxidative capacity on citrate cycle-derived substrates and fatty acids was analyzed by high-resolution respirometry.Results: Eight patients had left ventricular assist device (LVAD) implantation prior to heart transplantation ), and three patients did not receive mechanical circulatory support prior to transplantation . Myocardial mitochondrial reactive oxygen species (ROS) production was significantly decreased in the LVAD-HTX group compared to the HTX group (1.40 1 vs 0.90 1 pmol/(s*mg); p < 0.0001). There were no differences in either maximal oxidative capacity on fatty acids or citrate cycle-derived substrates, or on uncoupled respiration or mitochondrial coupling efficiency between the groups.Conclusions: These data suggest that ventricular unloading decreases myocardial mitochondrial ROS production in the setting of HF, whereas mitochondrial respiration remains unaffected. This mechanism may reveal a new target of ventricular unloading-dependent cardioprotection.Shiva Annamali, Michele Esposito, Sudeep Kuchibhotla, Shelley Hall, Theodore Schreiber, William O’Neill, Navin K. Kapur.Tufts Medical CenterBackground: Myocarditis complicated by cardiogenic shock (Myo-CS) remains a complex clinical problem. The use of acute mechanical circulatory support devices for cardiogenic shock is growing.Hypothesis: We explored the clinical utility of Impella trans-valvular micro-axial flow catheters in the setting of Myo-CS.Methods: We retrospectively analyzed data from 21 sites within the cVAD registry, an ongoing multicenter voluntary registry at sites in North America and Europe that have used Impella in patients with myocarditis. Myocarditis was defined by endomyocardial biopsy in 34% (n = 11) or by clinical history without angiographic evidence of coronary disease (n = 23).Results: A total of 34 patients who received Impella support for Myo-CS were identified. Mean age was 42 ± 17 years with 17 males, and a mean left ventricular ejection fraction (LVEF) on admission was 18 ± 10%. Baseline mean cardiac index was 1.8 ± 0.5 L/min/m2; pulmonary capillary wedge pressure was 25 ± 7 mmHg, and right atrial pressure was 22 ± 3 mmHg. Mean lactate was 27 ± 31 mg/dL. Additionally, 32% (n = 11) of patients required intra-aortic balloon pump, and 85% (n = 29) were requiring vasopressor/inotrope therapy prior to Impella placement. The Impella 2.5, CP, and 5.0 were used in 41% (n = 14), 35% (n = 12), and 24% (n = 8), respectively. Impella support was used for a mean duration of 90.56 ± 74.26 h. Mean LVEF improved from admission to discharge among myocarditis patients unsupported with Impella . In-hospital mortality was 38% (n = 13), and 47% (n = 16) of patients were discharged alive with 94% recovering without need for further device therapy .Conclusions: This is the largest analysis of Impella-supported myocarditis cases to date. The use of the Impella appears to be safe and effective in the settings of myocarditis complicated by cardiogenic shock.Julian Wiora, Patrick Horn, Christian Jung, Susanne Wolters, Tobias Zeus, Malte Kelm, Ralf WestenfeldUniversitaetsklinikum DuesseldorfBackground: Demographics are shifting to an elderly population with more comorbidities, potentially qualifying for mechanical circulatory support (MCS) during high-risk percutaneous coronary intervention (PCI) in order to maintain coronary perfusion pressure and hemodynamic stability. In this cohort, acute kidney injury (AKI) occurs frequently and is associated with increased short- and long-term mortality. Here, we compared clinical feasibility and incidence of AKI during high-risk PCI supported with peripheral VAECMO and Impella, respectively, in a single-center observational registry.Hypothesis: Time-to-MCS implementation of Impella MCS is less time consuming and reduces the incidence of AKI compared to peripheral VAECMO during MCS-supported high-risk PCI.Methods: Patients scheduled for elective MCS-supported high-risk PCI were included. All patients were turned down for surgery. Allocation to VAECMO (n = 10) or Impella (n = 11) was quasi random due to site-specific restrictions on the daily availability of the VAECMO platform. We analyzed PCI success, duration, peripheral complications , and contrast-induced nephropathy (CIN) defined as increase in serum creatinin by ≥ 0.3 mg/dl within 48 h.Results: Patient characteristics did not differ with respect to age (years) , prevalence of severely reduced LV-function , diabetes mellitus , GFR , days of hospitalization , and days on intense care unit . All patients were successfully revascularized, and the MCS was weaned at the end of the procedure. Device implantation time was significantly shorter in the Impella group . Likewise, procedure time tended to be shorter in the Impella cohort . Peripheral vascular complications were equally distributed . Importantly, despite similar risks for CIN as indicated by similar Mehran score  and a similar exposure to contrast medium , Impella-supported PCI was associated with a reduced incidence of CIN .Conclusions: MCS-assisted high-risk PCI with Impella support is associated with a lower incidence of contrast-induced nephropathy and a shorter time to MCS.Makoto Suzuki, Kenichi Hagiya, Ryosuke Higuchi, Itaru Takamisawa, Tetsuya Tobaru, Tetsuya Sumiyoshi, Mitsuaki IsobeSakakibara Heart InstituteBackground: We investigated whether pre-PCI procedural hypothermic mechanical support may provide clinical advantages in patients with profound cardiogenic shock complicating anterior STEMI.Methods: Of the 483 consecutive patients treated with PCI for a first anterior STEMI, including 31 patients with aborted sudden cardiac arrest in our database, a total of 37 consecutive patients with an anterior STEMI complicated with profound cardiogenic shock, defined as the presence of hyper-lactic acidemia (serum levels of lactate > 4 mmol/L), treated with mechanical circulatory support were identified. In accordance with a presence or absence of pre-PCI procedural therapeutic hypothermia, a prevalence of impaired myocardial tissue-level reperfusion, defined by angiographic myocardial blush grades 0 or 1 and in-hospital mortality were evaluated as the clinical outcomes.Results: Demographic characteristics revealed the mean age was 70 ± 14 years, 65% male, 41% hypertension, 49% diabetes mellitus, and serum levels of lactate of 7.8 ± 3.9 mmol/L. Median time from symptom onset to PCI was 80 min, and hospital admission to PCI was 52 min. All patients underwent PCI with mechanical circulatory support, and 13 patients were treated with pre-PCI procedural therapeutic hypothermia with a target core temperature of 34°C. Despite a similar achievement of post-PCI procedural TIMI flow grade III, less incidence of impaired myocardial tissue-level reperfusion was found in those with therapeutic hypothermia . Overall in-hospital mortality was 70%, which were composed of 6 patients with therapeutic hypothermia and 20 of 24 without therapeutic hypothermia . A logistic analysis demonstrated pre-PCI procedural therapeutic hypothermia as a potent contributor to in-hospital survival benefits (p = 0.006).Conclusions: The present study may provide a great possibility for pre-PCI procedural hypothermic mechanical support to ameliorate in-hospital clinical features in patients with a profound cardiogenic shock complicating anterior STEMI.Leo Buckley, Salvatore Carbone, Cory Trankle, Justin Canada, Claudia Oddi Erdle, Jessica Regan, Michele Viscusi, Dinesh Kadariya, Hayley Billingsley, Ross Arena, Antonio Abbate, Benjamin Van TassellVirginia Commonwealth UniversityBackground: Interleukin-1 is a pro-inflammatory cytokine and a key driver of systemic inflammation in acute heart failure (HF). In murine models, IL-1-driven inflammation acts as a direct cardiosuppressant and blunts the response to pharmacologic isoproterenol stress testing. In humans, plasma C-reactive protein level, a measureable readout of IL-1 activity, correlates with exercise capacity, and IL-1 blockade improves exercise capacity in both systolic and diastolic HF.Hypothesis: We hypothesized that IL-1 blockade improves LV contractility as measured by LV end-systolic elastance in acute HF.Methods: Acute HF patients were randomized to IL-1 blockade with IL-1 receptor antagonist (anakinra) or placebo for 14 days during hospitalization (n = 13) or within 2 weeks post-discharge (n = 40). LV end-systolic elastance was measured non-invasively as the slope of the LV end-systolic pressure-to-volume relationship . bIRNe in LV end-systolic elastance between baseline and 14 days in the placebo and anakinra groups was analyzed with the Wilcoxon rank sum test for within-group change over time.Results: There were no significant differences between anakinra and placebo patients with respect to age (p = 0.31), gender (p = 0.79), or high-sensitivity C-reactive protein (p = 0.94). Between baseline and 14 days, median % change in LV end-systolic elastance was 12%  in the anakinra group and 0% in the placebo group  (p = 0.08 for between-group difference). In the anakinra group, but not the placebo group, LV end-systolic elastance increased significantly , p = 0.03 vs baseline; for placebo 0 , p = 0.90 vs baseline). Pressure-volume area, a measure of myocardial work, did not change in either group (p > 0.19 for anakinra and placebo).Conclusions: In this small pilot study, anakinra significantly increased LV contractility without increasing myocardial work. These results are consistent with the hypothesized mechanism of action for IL-1 blockade in acute heart failure.Efstratios Katsianos, Georg Wolff, Manuel Stern, Christian Jung, Malte Kelm, Ralf WestenfeldUniversity Hospital Duesseldorf, Department of cardiologyBackground: Ventricular septal defect (VSD) is a rare but often fatal complication following myocardial infarction (MI). Patients with a ruptured septum usually present with the precipitous onset of hemodynamic compromise. Mortality of infarct-related VSD remains high; however, it varies significantly depending on the timing of surgical repair. Patients who underwent surgery within 7 days of presentation displayed 54% mortality, while delayed repair was associated with reduced mortality (18%). So far, the impact of left ventricular unloading using percutaneous mechanical circulatory support (MCS) on post-MI VSD has not been investigated.Hypothesis: We hypothesized that Impella support may facilitate delayed surgical repair in a patient with cardiogenic shock in acute MI complicated by VSD.Results: Case report: A 57-year-old male presented to the emergency department with angina pectoris for the last 5 days. He appeared diaphoretic in imminent shock (lactate 3.5 mmol/L). The 12-lead ECG revealed ST-elevations (> 2 mm) in the frontal leads (V2–V5). After unsuccessful volume challenge, norepinephrine was started (0.05 μg/kg/min) and increased rapidly during his transfer to the catheterization laboratory (0.2 μg/kg/min). Coronary angiography revealed a complete, subacute occlusion of the proximal left anterior descending (LAD) and corresponding severely reduced left ventricular function with apical and septal akinesia. In light of the further hemodynamic deterioration (lactate 6.5 mmol/L), we performed an oximetry run revealing a VSD . The decision was made to postpone surgical repair due to excessive mortality risk. Mechanical circulatory support with Impella CP was inserted, and the patient stabilized over the next days (lactate < 1.5 mmol/L). Nevertheless, intracardiac shunting increased (Qp:Qs ratio 2:3) over time, and a VSD repair with pericardial patch and left ventricular aneurysmectomy reconstruction was performed successfully on day 7. Postoperatively, the patient had an uneventful course and was discharged 15 days postoperatively.Conclusions: This case provides evidence that mechanical circulatory support with Impella may support a strategy of deferred surgery in patients with cardiogenic shock complicated by VSD. Ventricular unloading may create a window for scar formation bridging to secure surgical repair.Alexander Bernhardt, Mathias Hillebrand, MD; Yalin Yildirim, MD; Samer Hakmi, MD; Florian M. Wagner, MD; Stefan Blankenberg, MD; Hermann Reichenspurner, MD, PhD; Edith Lubos, MDUniversity Heart Center HamburgBackground: Left-sided unloading during extracorporeal membrane oxygenation (ECMO) therapy is crucial for the prevention of pulmonary edema and the facilitation of ventricular recovery. We present a case of a 55-year-old male patient under ECMO therapy with pre-existing LV thrombus formation in need of ventricular unloading.Methods: We implanted a 21 French TandemHeart Protekt Solo Transseptal cannula into the left atrium (LA) using a trans-septal approach via femoral vein. The cannula was connected to the venous line of the ECMO circulation. A flow probe and a clamp to reduce flow, if necessary, were attached to the LA line. LA flow was adjusted to 900 ml/min under transesoephageal echocardiography (TEE) control to keep the atrial septum in the midline and prevent suction of the inflow cannula.Results: After 9 days, the ECMO and TandemHeart cannula have to be weaned off stepwise and explanted. The patient was in NYHA class II without neurological sequelae . After 3 months, the patient has fully recovered and is working on a daily basis. The LV function is still moderately impaired and the LV thrombus is of the same size. The atrial septum showed no residual defect.Conclusions: Percutaneous transseptal insertion of the TandemHeart cannula incorporated in an ECMO circulation for the prevention of pulmonary oedema and subsequent weaning from extracorporeal circulation was feasible and safe in a patient with cardiogenic shock and LV thrombus.CA den Uil, LS Jewbali, AE Engstrom, AA Constantinescu, NM van MieghemErasmus Medical CenterBackground: Veno-arterial extracorporeal membrane oxygenation (VAECMO) is increasingly and successfully used to assist patients with refractory cardiogenic shock from different causes; however, it is currently not known which patients would benefit most from ECMO support.Hypothesis: Since ECMO may hamper left ventricular unloading and worsen left ventricular pressure/volume relations, the presence of predominant left ventricular failure in patients on VAECMO support may be associated with worse outcome. To study this hypothesis, we investigated outcome according to the presence of isolated left vs isolated right vs biventricular heart failure in patients with refractory cardiogenic shock of different causes.Methods: This single-center study included 132 patients with acute myocardial infarction (20%), acute on chronic heart failure (14%), post-cardiotomy (17%), cardiac allograft failure (8%), pulmonary embolism (16%), and acute non-ischemic heart failure (25%). Ventricular function was a priori assessed by transthoracic echocardiography (isolated left (26%), isolated right (22%), or biventricular heart failure (52%)). The primary endpoint was all-cause mortality at 90 days and long-term. Predictors for adverse outcome were identified by univariate and multivariate Cox regression analysis.Results: Median duration of ECMO support was 6 (3–9) days. Ninety-day survival was 51% . The main reason for withdrawal of ECMO support in patients with isolated LV failure was formation of extensive LV thrombus. The presence of isolated left ventricular failure was a predictor for 90-day mortality, irrespective of diagnosis and SAVE score. In patients who survived 90 days following ECMO implantation, long-term (4-year) survival was excellent .Conclusions: Isolated left ventricular failure was an independent predictor for dismal 90-day outcome. This finding questions the routine use of VAECMO in patients with refractory pure LV failure. Pure LV ventricular unloading (by means of last-generation dedicated Impella pumps) might be more suitable because these devices reduce afterload, decrease LV volumes, and thus actively unload the ventricle.Jörn Tongers, Jan-Thorben Sieweke, Christian Kühn, L. Christian Napp, Axel Haverich, Johann Bauersachs, Andreas SchäferHannover Medical SchoolBackground: Little progress has been made lately in cardiogenic shock (CS), and its mortality remains substantial in refractory CS. Hence, the evolving era of mechanical support is promising, although many aspects regarding the management of mechanical unloading remain uncertain.Hypothesis: We evaluate efficacy and prognostic predictors of early biventricular unloading in refractory CS.Results: In our single-center registry, 69 consecutive patients were analyzed . All patients required dual unloading by means of VAECMO plus Impella CP due to refractory CS . At admission and during the ICU course, patients were severely sick . Impella microaxial pump and VAECMO were inserted and removed percutaneously via femoral access . Reflecting clinical stabilization in response to mechanical support, number and dosing of catecholamines was rapidly reduced, while systolic arterial pressure increased . After censoring patients in whom ICU therapy was withdrawn because of their living will, 30-day mortality was considerably low (40%). Univariate Cox regression revealed shock duration until first device, infection, RV-failure, SAPS-II and SOFA scores, and lactate level after 12 h as variables determining success of unloading therapy. Shock duration until first device (cut-off 13.5 h), infection, and lactate levels after 12 h (cut-off 3.25) predicted outcome in multivariate analysis. In addition, biventricular failure significantly predisposed negative outcome.Conclusions: In conclusion, early biventricular unloading employing the Impella microaxial pump and VAECMO enables stabilization and rescue of refractory CS patients. Shock duration until initiation of support therapy, lactate levels at 12 h, and infections are multivariate predictors of CS survival.Shailendra Singh, Yonathon Litwok, Evelina Grayver, Perwaiz Meraj, Alexander Lee, Cindy GrinesNorthwell Health SystemBackground: The survival of patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains low despite early revascularization. The evolving percutaneous mechanical circulatory support (MCS) device options provide the possibility of a brighter future; however, markers are needed to assist in therapeutic decision-making when utilizing MCS in AMICS.Hypothesis: We investigated if early dynamic changes in lactate levels would reflect the therapeutic benefit of mechanical support and its potential impact on survival in patients presenting with AMICS. We hypothesized that earlier MCS implantation would result in improved lactate clearance and overall survival.Methods: Forty-six patients who presented to our coronary care unit underwent PCI and required MCS with an Impella 2.5 or Impella CP were included in this analysis. Differences between survivors and non-survivors were examined.Results: Mean patient age was 63.7 ± 11.2, 85% were men, and mean left ventricular ejection fraction was 27 ± 11.7%. Less use of vasopressors was found in the survival group . Adjunctive use of IABP had no impact on survival (p < 0.0866). Compared to pre-MCS lactate levels, survival demonstrated a significant decrease of 33.3% in lactate level obtained at 6 h, where as non-survivors had a slight increase in lactate level of 1.8% (p < 0.0001). Patients who had a lactate clearance of ≥ 30% at 6 h were 94% Survivors (p < 0.0001). Earlier MCS implantation was clearly exhibited in the survival group . In fact, survival was 82.4% (p < 0.0037) when the Impella device was implanted within 2 h of admission to the hospital.Conclusions: Patients who present with AMICS, serial lactate measurements may be used as a prognostic marker and therefore guide therapeutic decision-making. Early LV unloading with the Impella device and subsequent clearance of lactate improves survival in AMICS.Arianna Di Molfetta, R. Iacobelli, S. Filippelli, G. Grutter, G. Perri, F. Iodice, L. Pasquini, P. Guccione, A. AmodeoHospital Bambino Gesu, RomeBackground: Heart recovery in LVAD patients is related to reverse remodeling and unloading.Hypothesis: The aim of this study was to describe the echocardiographic trend of LV and RV function after pulsatile flow LVAD in pediatrics.Methods: From December 2013 to December 2016, we prospectively enrolled pediatric LVAD patients collecting clinical and echocardiographic data at the baseline, within 24 h after implantation and monthly until LVAD explant. Data were also used to calculate ventricular energetics parameters such as ventricular elastances, internal and external work, arterial elastance, and heart efficiency.Results: Thirteen patients affected by DCM were enrolled . Average LVAD stay was 226.2 ± 121.2 days, 70% were successfully transplanted, and 30% died. LV end-systolic/end-diastolic volumes/end systolic-pressure volume relationship were significantly reduced until 2 months follow-up (p = 0.019/p = 0.001/p = 0.002), but then they start to worsen over time. RV function improved in the acute phase, but then it started to decrease over time with a progressive RV enlargement. Since the 4-month follow-up, RV fractional area change (RVFAC) worsening was related with the deterioration of LV unloading (p = 0.0036). LV atero-ventricular coupling significantly decreased after the LVAD (p = 0.04). LV/RV mechanical efficiency is improved/worsened (p = 0.02) by the LVAD.Conclusion: Pulsatile LVAD in pediatrics is followed by an early and mid-term LV unloading that does not remain stable over time. RV function improved in the acute phase, but a progressive dilatation of RV was noted over time. The potential of heart recovery seems to be more promising during the early phase post LVAD.Sebastian Tume, Athar Qureshi, Dhaval Parekh, Antonio Cabrera, Ricardo Pignateli, Carlos Mery, Henri Justino, Iki AdachiTexas Children’s HospitalBackground: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) increases afterload, which can result in pulmonary edema and/or ventricular distention if used in a heart with diminished systolic function. A catheter-based percutaneous ventricular assist device (PVAD) has recently emerged as an option for ventricular decompression during ECMO support. Conversely, it is not rare for patients with progressive cardiogenic shock on PVAD support to require additional support with ECMO. Experience with combined PVAD and ECMO support in children is limited. We present our initial experience of such an approach.Methods: We conducted a retrospective chart review of all patients that underwent PVAD support in the setting of peripheral VA-ECMO at our institution. Data are presented as median (range).Results: Six patients having age 13 (6.5–19) years, weight 51 (22–74) kg, and BSA 1.46 (0.91–1.97) m2 met our inclusion criteria: biventricular (n = 5) and univentricular physiology (n = 1). PVAD support was with Impella® 2.5 (n = 2) and CP (n = 4). While PVAD was placed using the femoral artery in all patients, ECMO was initiated via the central cannulation (n = 1), femoral (n = 4), or neck (n = 1) vessels. In four patients, ECMO was added 6 (0–15) hours after PVAD initiation to optimize perfusion. In the other two patients, PVAD was added after ECMO support for ventricular decompression, resulting in 6% reduction in LVEDD (35 to 33 mm) in one patient and 32% reduction in PCWP (19 to 13 mmHg) in the other. Duration of simultaneous PVAD and ECMO support was 6 (5–12) days. Hemolysis markers at 5 days of combined support remained in clinically acceptable ranges: LDH 1632  U/L and plasma free hemoglobin 33 (30–150) mg/dL. There were, no major complications. However, PVAD insertion site bleeding was common (83%). In all patients, ECMO was weaned off after 6.5 (5–12) days of support, with PVAD remaining in place. Subsequently, PVAD support was discontinued 0.5 (0.5–5) days after ECMO decannulation. All patients survived support, and two patients expired at 7 and 23 days after support.Conclusions: We describe the feasibility of PVAD as an adjunctive therapy to VA-ECMO support in children. The risk profiles of the combined support are not deemed substantially higher than those for ECMO alone. Its potential advantages include ventricular decompression and facilitation of ECMO weaning process. Further studies are warranted to clarify the safety and efficacy of such an approach in the pediatric population.Gianluigi Perri, A. Di Molfetta, S. Filippelli, M.G.Gagliardi, A. Rizza, P. Guccione, A. AmodeoHospital Bambino Gesu, RomeBackground: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an established mechanical circulatory support (MCS) used to treat acute heart failure (HF) in adults and pediatric patients; however, the long-term efficacy is limited by the lack of direct left ventricular (LV) unloading.Hypothesis: We present a trans-carotid Impella 2.5 implantation technique in a pediatric patient with peripheral VA-ECMO.Methods: A 15-year-old boy  was admitted for acute rejection after HF with a progressive cardiogenic shock requiring peripheral VA-ECMO. The patient developed progressive central venous pressure (CVP) increase with inadequate LV unloading, severe pulmonary edema, and progressive renal failure. It had been decided to implant a microaxial Impella 2.5 left ventricular assist device (LVAD) through a surgical trans-carotid approach because of its limited femoral artery size.Results: A right cervicotomy was performed, and the medial and lateral border of sternocleidomastoid muscle were dissected, and carotid sheet was incised to expose the right common carotid artery (CCA) that was approximately 6 mm. A PTFE tube graft was end-to-side anastomosed to the CCA. The 2.5 Impella was inserted through the graft in the right CCA and advanced across the aortic valve inside the LV under fluoroscopic and transesophageal echocardiographic guidance. The ECMO support was initially maintained at 2.8 L/min and Impella at 1.4 L/min. Then, it progressively increased to 3 L/min and 1.9 L/min, respectively. Ten days later, the patient was successfully transplanted.Conclusion: This is the first report of transcarotid percutaneous Impella implantation in a pediatric patient. Placement of a Goratex graft is an easy technique to optimize the insertion of the Impella 2.5 axial flow pump via CCA and minimize or avoid the vessel complications and inadequate cerebral flow. This approach might be an alternative and feasible option in pediatrics patients, affected by severe LV failure, as bridge to decision, or bridge to candidacy.Hermann Reichenspurner, Alexander BernhardtUniversity Heart Center HamburgSecondary Left Ventricular (LV) Unloading After Transportation in Patients After Out-of-Hospital Extracorporeal Life Support (ECLS) Implantation Improved Survival and Probability of Successful WeaningBackground: ECLS is an established and recommended treatment modality in patients with acute carcinogenic shock. Safety and feasibility of this technique increased this treatment to out-of-hospital implantation and transportation. LV unloading in patients on ECLS has shown to increase survival and probability of successful weaning from short-term mechanical circulatory support (MCS). Here, we present our treatment algorithms and outcomes after ECLS implantation and transportation outside our own center.Methods: Between October 2014 and March 2017, a total number of 47 consecutive patients  received ECLS in a referring institution. Of those, 29 (61.7%) received arterial-venous (VA) ECLS implantation using a femoral percutaneous approach. Prospective collected data were retrospectively analyzed for survival and weaning depending on LV unloading.Results: The 30-day survival in the VA ECLS patients was 41.4%. Nine patients received an additional Impella 2.5 device for LV unloading after a mean time of 7.6 h, and one patient received an LA cannula after ECLS implantation and transportation to our center. Survival in patients with LV unloading was higher compared to those without LV unloading . Approximately 50% of LV-unloaded patients were weaned from MCS vs 31.6% without additional LV unloading (p = 0.08). Two patients on ECLS and Impella 2.5 support were successfully bridged to Impella 5.0 support, with one patient weaned off later and one patient bridge to a durable assist device.Conclusions: Secondary Impella 2.5 implantation in patients who have successfully received ECLS in a referring hospital improved survival and weaning from the short-term device and is therefore recommended in transported ECLS patients.Krishnaraj S Rathod, Sudheer Koganti, M. Bilal Iqbal, Ajay K Jain, Zoe Astroulakis, Roby Rakhit, Miles C. Dalby, Tim Lockie, Iqbal S. Malik, Charles J Knight, Mark Whitbread, Anthony Mathur, Simon Redwood, Philip A. MacCarthy, Constantinos O’Mahony, Andrew Wragg, Dan JonesSt. Bartholomew’s HospitalBackground: Cardiogenic shock (CS) remains a major cause of morbidity and mortality in patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the current trends in CS management, looking specifically at the incidence, use of intra-aortic balloon pump (IABP) therapy, and outcomes in patients with STEMI treated with primary percutaneous coronary intervention (PCI).Methods: We undertook an observational cohort study of 21,210 STEMI patients treated between 2005 and 2015. Patients’ details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society (BCIS) PCI dataset. In this dataset, there were 1890 patients who presented with cardiogenic shock. Primary outcome was all-cause mortality at a median follow-up of 4.1 years (IQR range 2.2–5.8 years).Results: Increasing rates of cardiogenic shock were seen over the course of the study with consistently high mortality rates of 45–70%. Exactly 685 patients underwent IABP insertion during primary PCI for CS with decreasing rates over time. Those patients undergoing IABP therapy were younger, more likely to have poor LV function, and less likely to have had previous PCI compared to the control group. Procedural success rates were similar  although crude, in-hospital major adverse cardiac events (MACE) rates were higher  in patients undergoing IABP therapy. Kaplan-Meier analysis demonstrated significantly higher mortality rates in patients receiving IABP therapy  during the follow-up period. After multivariate Cox analysis (HR 1.01 95% CI 0.57–1.77) and the use of propensity matching (HR 1.35 95% CI 0.84–1.61), IABP therapy was not associated with mortality.Conclusions: Cardiogenic shock treated by PCI is increasing in incidence and remains a condition associated with high mortality and limited treatment options. IABP therapy was not associated with a long-term survival benefit in this cohort and may be associated with increased early morbidity.Arvind BhimarajHouston Methodist.Background: Patients in cardiogenic shock and multiorgan failure are considered too sick for a direct durable left ventricular assist device (LVAD) placement. Impella 5.0 can provide sufficient support in this setting and can be used as a bridge to durable LVAD placement.Hypothesis: Impella 5.0 can be used as a bridge for durable LVAD.Methods: We performed a single-center retrospective review of all consecutive patients supported with Impella 5.0 from August 2014 to October 2016 and identified those bridged to a durable LVAD.Results: A total of 36 Impella 5.0 devices were implanted through an axillary graft in our institution. Of those, seven were used as a bridge for a durable LVAD (HMII). The main indication for implant was acute decompensated heart failure on chronic heart failure (5/7), and two were postsurgical (TAVR and CABG). The majority were Caucasian males with a median age of 61.2. Median length of hospital stay was 43 days, and median length of Impella support was 12 days (range 4–31). All patients had MCS at the time of Impella implant:six6 had IABP and one had VA ECMO. No pump dysfunction or replacement was seen for the duration of Impella support; only one patient required pump repositioning. All patients were ambulating and working with physical therapy at the time of durable LVAD implant. Four (4/7) survived to discharge post LVAD surgery.Conclusions: Implantation of Impella 5.0 through axillary graft can be used as a strategy to stabilize patients in severe cardiogenic shock and improve their candidacy for a durable LVAD-support.Shiva Annamalai, Michele Esposito, Xiaoying Qiao, Yali Zhang, Lara Reyelt, Courtney Boggins, Kevin Morine, Richard H Karas, Navin KapurTufts Medical CenterBackground: Mobility is an important indicator of recovery for patients with cardiogenic shock (CS). No studies have quantified peak mobility for patients with CS who are supported with the Impella 5.0 acute mechanical circulatory support (AMCS) device.Hypothesis: The purpose of our study was to evaluate mobility levels among patients with CS being treated with an axillary Impella 5.0 pump.Methods: We retrospectively analyzed data from 19 patients receiving an Impella 5.0 device for CS at our institution from 2013 to 2016. We used the Johns Hopkins Highest Level of Mobility (JH-HLM) Scale to quantify maximum mobility level achieved during active Impella 5.0 support. Higher scores on a scale of 1 to 8 indicated more mobility. Activity Measure for Post Acute Care (AM-PAC) Score was quantified for each patient to assess activity limitations, with a maximum score of 24.Results: The mean age of the total cohort was 60 ± 12 years, and the mean left ventricular ejection fraction (LVEF) was 16 ± 6%. In-hospital mortality was 47% (n = 9). Of the 19 Impella 5.0 implants, 10 survived, 6 died from withdrawal of care, and 3 died from worsening heart failure/cardiogenic shock. Baseline clinical characteristics were similar between groups (Table 1). Of the survivor cohort, indications for device therapy were acute decompensated heart failure , ST-segment elevation myocardial infarction , and myocarditis (n = 2). Of the non-survivor cohort, indications included ADHF (n = 4), STEMI (n = 4), and post-cardiotomy CS (n = 1). Similar rates of mobilization during the time of Impella implant were seen between groups. Compared to non-survivors, survivors achieved a higher maximum JH-HLM level but similar AM-PAC scores .Lazarus I prospective study of functional status after Impella 5.0 implantation.Conclusion: Maximum mobility level after Impella 5.0 implantation may be associated with improved survival. The clinical utility of exercise as a therapeutic intervention for patients requiring prolonged AMCS requires further study. Based on these findings, we will report the design of the Arianna Di Molfetta, Gianfranco Ferrari, Roberta Iacobelli, Sergio Filippelli, Gianluigi Perri, Antonio Amodeo.Hospital Bambino Gesu, RomeBackground: Left ventricular assist devices (LVADs) are used to bridge pediatric patients to transplantation; however, the effects of LVADs on right ventricular (RV) function is controversial.Hypothesis: This work aims at studying the ventricular interdependency in the presence of continuous (c-) and pulsatile (p-) flow LVAD in pediatric patients using a lumped parameter model including the representation of the septum.Methods: Five pediatric patients’ data were used to simulate patients’ baseline. The effects on LV and RV functions, energetics, preloads, and afterloads of different c-LVAD speeds, p-LVAD rate, p-LVAD systole duration, p-LVAD filling, and ejection pressures were simulated.Results: c-LVAD and p-LVAD unload the LV decreasing the LV external work and improving the LV ventriculo-arterial coupling, and these effects are more evident increasing the c-LVAD speed and the p-LVAD rate. c-LVAD and p-LVAD decrease the RV afterload, increase the RV ejection fraction, and improve the RV ventriculo-arterial coupling. The changes in RV function are inversely proportional to the degree of the interventricular septum leftward shift that increased by increasing the LVAD contribution.Conclusion: The study of the interventricular interaction could lead to the development of a dedicated algorithm to optimize LVAD setting in pediatric population.Arianna Molfetta, L. Casadio, L. Fresiello, R. Iacobelli, S. Filippelli, G.Perri, G. Ferrari, P. Guccione, S. Jacobs, B. Meyns, M. Massetti, A. AmodeoHospital Bambino Gesu, RomeBackground: Heart remodeling during left ventricular assist device (LVAD) support is one important fact that can influence the possibility of heart recovery.Hypothesis: We aimed at studying the evolution of left ventricular (LV) and right ventricular (RV) loading condition in LVAD patients comparing pulsatile (PVAD) and continuous flow (CVAD) LVAD.Methods: Clinical and echocardiographic data of 19 PVAD pediatric patients were retrospectively collected and compared to literature data of 35 CVAD young adult patients to assess the changes in ventricular loading from baseline to follow up of 1, 3, and 6 months.Results: Mean values of left ventricular ejection fraction improved from 22 ± 15 to 32.8 ± 13.9% in PVAD and from 21.1 ± 9.5 to 46 ± 20.6% in CVAD. In both cases, the major ejection fraction increment occurred during the first 30 days of LVAD. In CVAD, LV end-diastolic and end systolic diameters  decreased progressively over time from 58.4 ± 22.8 to 52.7 ± 9.3 mm  and from 54.3 ± 21.2 to 40.1 ± 13.8  in 6 months. In PVAD, LVEDD and LVESD decreased significantly at 1-month follow-up from 46.4 ± 9.2 to 34.2 ± 6.6 mm  and from 40.9 ± 10.5 to 29.2 ± 7.4 mm , but then a new LV enlargement was observed coming almost at the same diameters measured at baseline. In CVAD, RV function and dimensions decreased progressively, while RV dimensions progressively increased in PVAD, and RV function started to deteriorate since the 3-month follow-up.Conclusion: At short-term follow-up, the LV unloading is higher in PVAD than in CVAD population. On the contrary, at long-term follow–up, the LV unloading provided by the CVAD is higher than in the PVAD population. Finally, RV function and dimensions are improved by CVAD, while they are worsened by PVAD.


Optimal lead positioning is an important determinant of cardiac resynchronization therapy (CRT) response.The purpose of this study was to evaluate cardiac computed tomography (CT) selection of the optimal epicardial vein for left ventricular (LV) lead placement by targeting regions of late mechanical activation and avoiding myocardial scar.Eighteen patients undergoing CRT upgrade with existing pacing systems underwent preimplant electrocardiogram-gated cardiac CT to assess wall thickness, hypoperfusion, late mechanical activation, and regions of myocardial scar by the derivation of the stretch quantifier for endocardial engraved zones (SQUEEZ) algorithm. Cardiac venous anatomy was mapped to individualized American Heart Association (AHA) bull’s-eye plots to identify the optimal venous target and compared with acute hemodynamic response (AHR) in each coronary venous target using an LV pressure wire.P = .36). SQUEEZ-derived guidance produced a positive AHR in 92% of target segments, and pacing in a CT-SQUEEZ target vein produced a greater clinical response rate vs nontarget segments (90% vs 60%).Fifteen data sets were evaluable. CT-SQUEEZ–derived targets produced a similar mean AHR compared with the best achievable AHR (20.4% ± 13.7% vs 24.9% ± 11.1%; Preprocedural CT-SQUEEZ–derived target selection may be a valuable tool to predict the optimal venous site for LV lead placement in patients undergoing CRT upgrade.  Patients with existing pacing systems, left ventricular (LV) systolic impairment, and a high proportion of right ventricular (RV) pacing benefit from cardiac resynchronization therapy (CRT).The study complied with the Declaration of Helsinki, and the protocol was approved by the local ethics committee. Informed consent was obtained from each patient. Between September 2014 and July 2016, we prospectively recruited 18 patients with a preexisting pacemaker/implantable cardioverter-defibrillator, persistent heart failure symptoms on optimal medical therapy, LV ejection fraction <45%, and >50% RV pacing.Patients underwent clinical assessment (New York Heart Association score and Minnesota Living with Heart Failure questionnaire), 6-minute walk test, cardiopulmonary exercise test, and 2-dimensional transthoracic echocardiography. Ischemic cardiomyopathy (ICM) was defined by prior myocardial infarction, coronary angiography demonstrating severe coronary disease and subsequent revascularization, and/or CMR evidence of myocardial fibrosis. Absence of these features inferred non-ICM.Xres smooth reconstruction kernel. Iterative reconstruction using the iDose4 algorithm (range 1–7) was used to reduce image noise and radiation dose. The cardiac CT scan was evaluated by an independent Society of Cardiovascular Computed Tomography Level III cardiac CT expert (R.R.). First-pass contrast-enhanced sequences were analyzed using standardized multiplanar reconstruction windows according to the AHA nomenclature for regional segmentation. End-diastolic myocardial wall thickness was evaluated reviewing each myocardial region in both short- and long-axis views. Areas of hypoperfusion were evaluated systematically with slice width thickness increased to 5 mm and display window and level settings adjusted to 100 and 200 HU, respectively. Abnormal perfusion was defined as myocardium exhibiting significantly reduced contrast distribution visually compared against attenuation of normal myocardium in each patient used as an internal reference. Where discrepancies existed, a 50 HU difference between normal and hypoperfused myocardium was usedPatients underwent cardiac CT using the Brilliance iCT 256-slice MDCT scanner  before upgrade. Intravenous metoprolol was used to achieve a heart rate of <65 beats/min in sinus rhythm and <100 beats/min in atrial fibrillation. A total of 120 mL of intravenous contrast  was injected (5 mL/s) via a power injector into the antecubital vein. Descending aorta contrast-triggered (180 Hounsfield units [HU]), electrocardiogram (ECG)–gated scanning was performed with single breath-hold technique after a 10- to 12-second delay. Scanning parameters included a heart rate–dependent pitch of 0.2–0.45, a gantry rotation time of 270 ms, a tube voltage of 100 or 120 kVp depending on the patient’s body mass index, and a tube current of 125–300 mA depending on the thoracic circumference. A second single-phase ECG-gated scan was acquired 12 minutes after the initial contrast bolus for myocardial scar imaging; the tube voltage was reduced by 20 kVp while the tube current was increased proportionally to account for an increase in image noise.We adopted a pragmatic approach for identifying regions of delayed enhancement as previously described.cc), the criterion standard for noninvasive regional strain, using tagged CMR sequences in a canine model of myocardial infarction.High-contrast disparity between LV blood pool and myocardium permits the identification and tracking of finely engraved endocardial surface features. The SQUEEZ method uses these features to track endocardial material points over the heart cycle to calculate regional cardiac function using the following formula:ch point . This meSQUEEZ-derived regional function data were merged with individual patient anatomy. Septal segments were excluded as targets. SQUEEZ-derived strain curves with low amplitude strain (LAS) <10% shortening were judged nonviable and excluded as targets .max, mm Hg/s). AHR was compared with CT indices and the sensed QLV interval at each pacing site.CRT upgrade was performed with a quadripolar LV lead in 17 patients (94%) and a bipolar lead in 1 because of unfavorable venous anatomy. Nine patients (50%) received CRT with defibrillator; 1 patient required an additional RV shock lead; and the remaining 8 already having preexisting implantable cardioverter-defibrillators. Identification of the optimal hemodynamic site for LV stimulation was performed by measuring acute hemodynamic response (AHR) using an 0.014-in high-fidelity Certus RADI PressureWire  in the LV cavity via a retrograde arterial approach as previously described.t test; those with a non-Gaussian distribution were compared using the Wilcoxon matched-pair signed rank test. Categorical data were presented as absolute number of occurrences and associated frequency (%). Analysis of variance was used to compare >2 groups. The results were considered significant at a P value of <.05.Continuous data were presented as mean ± SD. Those with Gaussian distribution were compared using a paired The patient demographic characteristics are summarized in 2). Patients were supine for 15 ± 1 minutes. Studies were independently assessed using the Society of Cardiovascular Computed Tomography quality scoreAll CT scans were successfully completed . Lateral and posterolateral veins produced the best AHR irrespective of etiology. The lateral vein stimulation produced greater AHR than did the anterior vein  (max (positive AHR)Eighteen patients underwent successful LV lead implantation, and 15 of 18 had full hemodynamic and CT data sets. In 1 patient a RADI wire was not sited because of arterial access, and 2 patients had CT scans of insufficient quality for analysis. CT-SQUEEZ analysis identifying the target epicardial vein subtending the area of LMA excluding LAS regions (inferring scar) was compared with all sites where AHR was measured (3 ± 1 coronary veins per patient). AHR (mean % change) was as follows: 2.5% ± 8.8%, anterior; 14.5% ± 11.5%, anterolateral; 23.2% ± 7.7%, lateral; 21.8% ± 15.0%, posterolateral; and 12.4% ± 5.1%, posterior  . NotablyP = .36). Targeting electrical latency  achieved a similar AHR . Pacing scar produced the lowest AHR  comparable to the worst achievable AHR . AHR and QLV interval weakly correlated in 63 paired data sets . The AHR of locations with QLV interval >100 ms but in scar was significantly lower than that of nonscarred locations   .Figure 4P < .001 and Minnesota Living with Heart Failure questionnaire scores 32 ± 24 vs 39 ± 19; P = .03) and were able to walk on average 92 m further over 6 minutes. The paced QRS duration was shorter , LV ejection fraction increased , and N-terminal pro-brain natriuretic peptide level decreased . Patients paced in CT-SQUEEZ targets had greater clinical response than did those paced in nontarget segments  (P = .07).At 6 months, patients symptomatically improved  . Hundred1.P = .36).CT-SQUEEZ targets produced a mean AHR similar to the best achievable AHR .The principal findings were as follows:We demonstrate the novel utility of preprocedural CT for LV lead guidance to regions of LMA devoid of LAS. P = .17). The mean AHR was similar in CT targets compared with the QLV interval , and the animals had no preexisting pacing systems. The development of dual energy source CT scanners holds promise in improving differentiation between subtle soft tissue characteristics and may be able to more reliably demonstrate myocardial fibrosis.cc) in an animal model, suggesting that it is sensitive enough to demonstrate local regional motion differences and remain a useful tool to assess dyssynchrony.NCT01464502).Modern single energy source CT scanners are currently unable to accurately delineate extracellular myocardial fibrosis through late contrast enhancement. While iodinated contrast displays similar kinetic properties to gadolinium-DTPA (diethylenetriamine penta-acetic acid) and can demonstrate acute hypoperfusion from ischemic injury, reliable visualization of chronic fibrosis with late enhancement occurred in only 1 patient. We therefore used local wall thinning (<6 mm) and/or hypoperfusion to infer scar, and the low AHR in these segments is in keeping with scar despite the lack of visualization  and 5. TPreprocedural CT-SQUEEZ–derived target selection may be a valuable tool to predict the optimal venous site for LV lead placement by guiding the implanter toward late activating regions, away from areas of scar.


Cardiac amyloidosis (CA) is generally characterized by a poor prognosis and significantly increased mortality. Although right ventricular (RV) dysfunction is strong predictor of outcome in AL amyloidosis, there are limited data regarding the prognostic significance of RV size. We sought to investigate whether cardiovascular magnetic resonance (CMR) assessment of RV size has prognostic value in CA.Consecutive patients referred for CMR for possible CA were retrospectively evaluated. Diagnosis of CA was based on that all patients had positive Congo red staining of biopsy , and the presence of a typical pattern of subendocardial late gadolinium enhancement. The patients underwent CMR with measurement of left ventricular (LV) and RV volumes, mass and ejection fraction.2 predicted mortality, .69 patients , age 60 ± 11 years) were included, CA was diagnosed in 47 (68.1%). Age, gender, New York Heart Association class, medications, serological biomarkers, and electrocardiographic voltage were recorded. The parameters measured by MRI were also recorded, such as the left ventricular end-diastolic volume (LVEDV), the right ventricular end-diastolic volume (RVEDV), the left ventricular mass (LV mass). Mean age was 61 ± 10 years with 28 men (59.5%) in CA. New York Heart Association class >II was noted in 24 patients (51.1%) and low voltage on electrocardiogram  in 23(48.9%). At a median follow-up of 21 months, there were 27 deaths (55.3%). On univariate Cox regression analysis, New York Heart Association class>II, the left ventricular mass index (LV massi), the right ventricular ejection fraction (RVEF), the right ventricular end-systolic volume index (RVESVI) were associated with increased mortality. On multivariable Cox proportional analysis, only RVESVI was significantly associated with increased mortality . RVESVI had the better reliable diagnostic power for survival compared with NYHA class by ROC curves, with an area under the curve equal to 0.738.The receiver-operator characteristic curve-derived cut-off value of RVESVI of 32 mL/mOur data show that in patients with Cardiac Amyloidosis, the right ventricular end-systolic volume index is a powerful, independent predictor of longer-term survival. Cardiovascular magnetic resonance assessment of RV size is important in the evaluation and risk stratification of in these patients.


To evaluate cardiovascular function in boys with Duchenne (DMD) and Becker (BMD) muscular dystrophy, using cardiac magnetic resonance (CMR).N = 12) were under treatment with both deflazacort and perindopril, while Group B (n = 12) were under treatment with deflazacort, only. BMD patients did not take any medication. Biventricular function was assessed using a standard SSFP sequence. Late gadolinium enhancement (LGE) was assessed from T1 images taken 15 min after injection of 0.2 mg/Kg gadolinium DTPA using a 3D–T1-TFE sequence.This is a single point cross sectional study of twenty-four boys with genetically ascertained DMD, and 10 with BMD, aged 10.5 ± 1.5 years (range 9–13), were prospectively evaluated by a 1.5 T system and compared with those of age-sex matched controls. The DMD patients were divided in 2 groups. Group A (p < 0.001). An epicardial LGE area = 3 ± 0.5% of LV mass was identified in the posterolateral wall of LV only in 6/12 patients of Group B, but in not in any BMD or Group A.Group A and BMDs were asymptomatic with normal ECG, 24 h ECG recording and echocardiogram. Group B were asymptomatic but 6/12 had abnormal ECG and mildly impaired LVEF. Their 24 h ECG recording revealed supraventricular and ventricular extrasystoles . LV indices in Group A and BMD did not differ from those of controls. However, LV indices in Group B were significantly impaired compared with controls, Group A and BMDs (Children with either BMD or DMD under treatment with both deflazacort and perindopril present preserved LV function and lack of LGE. However, further large scale multicenter studies are warranted to confirm these data, including further CMR mapping approaches. Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder affecting 1 in 3500 males , due to , present a loss of ambulation between ages 7 and 12 years. Cardiomyopathy and respiratory muscle dysfunction occur several years after the onset of neuromuscular symptoms and contribute to death usually in the 20s, with the chance of surviving to age 25–30, due to advances in respiratory care. The ECG is abnormal in 90% of cases, demonstrating tall R waves, increased RS in V1 and deep narrow Q waves in left precordial leads. Sinus tachycardia is the commonest abnormality. Atrial fibrillation, flutter and ventricular premature complexes can also be found. The main cause of death is heart failure; however, the clinical presentation of heart disease in DMD is masked by muscle weakness contributing to reduced physical activity . The MRI-MASS, Medis, Leiden, the Netherlands software was used and the readers were blinded to the clinical data (10).p < 0.05.All measurements were expressed as mean ± SD. Statistical significance of the differences was investigated using unpaired Student’s T-test. Correlation between variables was sought with Pearson’s correlation coefficient. For non-parametric data the Mann-Whitney test and Spearman’s correlation coefficient were used respectively. Statistical significance was considered for p < 0.05), but they did not differ in heart rate or blood pressure  were seen in the same 6 patients concurrently. The 24 h ECG recording revealed rhythm disturbances, including sinus tachycardia, supraventricular and ventricular extrasystolic beats . No bradycardia, ventricular tachycardia and/or atrioventricular block were identified in any of them. BMD patients were asymptomatic, with normal resting ECG, 24 h ECG recording and echocardiogram.p < 001). An epicardial LGE area = 3 ± 0.5% of LV mass was identified in the posterolateral wall of LV only in 6/12 patients of Group B , which is also characterized by CMR detectable LGE, that is significantly associated with the immunohistologically detected intramyocardial inflammation . HoweverRecently, it was documented that also LGE-spared regions of boys with DMD have significantly different native T1 and ECV values compared to controls and native T1 measurements can identify early changes in DMD patients without the presence of LGE and predict disease severity more effectively than ECV . HoweverAlthough some of DMD patients presented early ECG changes and ECG is a cheap and widely available tool, the absence of ECG changes in DMD can not exclude the cardiac involvement . FurtherIn this context, CMR seems to be the only objective way to early detect asymptomatic myocardial involvement in dystrophinopathies. However, in early childhood a CMR evaluation may be problematic, because it may need sedation and there may be long term issues with repeated use of gadolinium. However, the recent application of native T1 mapping gives more reliable information than LGE with the additional advantage of not using contrast agent .Another important point is the effect of steroids in DMDs. A recent study evaluating the effects of steroid use alone or in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blocker (ARB) using cardiovascular magnetic resonance (CMR) derived circumferential strain did not document any significant difference . HoweverThe current study has the limitation of a relatively small population sample. We also did not pursue either a short or a long term follow up. Additionally, T1 mapping measurements, which could potentially reveal additional abnormalities as compared to LGE alone, were not available.Finally, the study design can not definitely support that perindopril is protective in DMD, because the selection of patients with and without perindopril was not random, but subject to tolerance. Also, as a cross-sectional study, it can only show association, and neither causation nor progression. However, we strongly believe that if our study will be published, it can motivate further longitudinal cohort studies that may show more supportive results.Children with either BMD or DMD under treatment with both deflazacort and perindopril present preserved LV function and lack of LGE. However, further large scale multicenter studies are warranted to confirm these data, including further CMR mapping approaches.


Myocardial strain is increasingly recognized as an important assessment for myocardial function. In addition, it also improves outcome prediction. However, there is lack of standardization in strain evaluation by cardiovascular magnetic resonance (CMR). In this study we compared strain values using multiple techniques and multiple vendor products.N = 77) and healthy controls (N = 10) underwent CMR on a 1.5 T scanner. Tagging, displacement encoding with stimulated echoes (DENSE) and balanced stead state free precession cine imaging were acquired on all subjects. A single matched mid left ventricular (LV) short axis plane was used for the comparisons of peak circumferential (Ecc) and radial strain (Err) and a 4-chamber view for longitudinal strain (Ell). Tagging images were analyzed using harmonic phase (HARP) and displacement encoding with stimulated echoes (DENSE) images using a proprietary program. Feature tracking (FT) was evaluated using 3 commercially available software from Tomtec Imaging Systems, Cardiac Image Modeller (CIM), and Circle Cardiovascular Imaging. Tagging data were used as reference. Statistic analyses were performed using paired t-test, intraclass correlation coefficient (ICC), Bland Altman limits of agreement and coefficient of variations.Prospectively recruited patients with cardiomyopathy of diverse etiology (Average LV ejection fraction was 50% (range 32 to 62%). Regional LV wall motion abnormalities were present in 48% of the analyzed planes. The average Ecc was − 13 ± 4%, − 13 ± 4%, − 16 ± 6%, − 10 ± 3% and − 14 ± 4% for tagging, DENSE, Tomtec, CIM and Circle, respectively, with the best agreement seen in DENSE and Circle with tagging. The Err was highly varied with poor agreement across the techniques, 32 ± 24%, 40 ± 28%, 47 ± 26%, 64 ± 33% and 23 ± 9% for tagging, DENSE, Tomtec, CIM and Circle, respectively. The average Ell was − 14 ± 4%, − 8 ± 3%, − 13 ± 5%, − 11 ± 3% and − 12 ± 4% for tagging, DENSE, Tomtec, CIM and Circle, respectively with the best agreement seen in Tomtec and Circle with tagging. In the intra- and inter-observer agreement analysis the reproducibility of each technique was good except for Err by HARP.Small but important differences are evident in Ecc and Ell comparisons among vendors while large differences are seen in Err assessment. Our findings suggest that CMR strain values are technique and vendor dependent. Hence, it is essential to develop reference standard from each technique and analytical product for clinical use, and to sequentially compare patient data using the same software.The online version of this article (10.1186/s12968-018-0448-9) contains supplementary material, which is available to authorized users. Myocardial strain is increasingly recognized as an important myocardial performance index , 2. It cStrain can be analyzed using a number of techniques by cardiovascular magnetic resonance (CMR) . Tagged 2). All study participants completed a questionnaire for demographic information and medical history.The study protocol was approved by the Institutional Review Board. All participants were recruited prospectively after obtaining written informed consent. Healthy subjects were recruited if they did not have cardiovascular history or risk factors and had normal electrocardiogram (ECG) and transthoracic echocardiogram. Patients with arrhythmia at the time of CMR were excluded from the analysis. Additional exclusion criteria were any contraindication to CMR , allergic reaction to gadolinium based contrast agent or impaired renal function  48 ms to 84 ms, average temporal resolution 50 ms, flip angle 58° to 70°, image matrix 192 × 192 for long axis and 154 × 192 for short axis planes, average voxel size 1.3 × 1.3 × 6 mm3 for long axis and 1.6 × 1.3 × 8 mm for short axis views. Image was reconstructed with interpolation. The average breath hold was ~ 12 s.All subjects underwent CMR imaging in a 1.5 T Avanto scanner . A combination of 16-elements phased array surface coil and spine coil were used. LV volumes and systolic function were assessed using breath-hold balanced steady state free precession cine images with retrospective ECG gating. A stack of LV short axis planes and three long axis planes  were obtained by using the following imaging parameters: field-of-view (FOV) = 240 × 240 mm2, TR 78.0 ms, (echo time) TE 4.0 ms, grid tag spacing 8 mm, flip angle 12°, echo spacing 8.8 ms, with voxel size 1.4 × 1.4 × 6 mm3. Image was reconstructed with interpolation. The average breath hold was ~ 18 s.Complementary spatial modulation of magnetization (CSPAMM) tagged imaging used a spoiled gradient echo grid-tag cine sequence and retrospective ECG gating. The retrospective ECG gating was chosen because the reconstructed images began close to 0 ms for the first frame matching that of feature tracking as opposed to 20 to 25 ms offset by the prospective gating. The typical sequence parameters were as follows: FOV 270 × 360 mm2, flip angle = 20°, TR = 15 ms, TE = 1 ms, number of spiral interleaves = 6, temporal resolution = 30 ms, displacement encoding frequency = 0.1 cycles/mm and voxel size 2.8 × 2.8 × 8 mm3. The average breath hold was ~ 23 s. On average, 80% of the cardiac cycle was captured.A CSPAMM spiral cine DENSE pulse sequence with prospective ECG gating was used to acquire DENSE images with displacement encoding applied in two orthogonal in-plane directions. A combined acquisition of both displacement encoding directions was obtained. The imaging parameters included FOV = 360 × 360 mm2, TE 3.17 ms, TR = 1 × RR interval, flip angle 25°, voxel size 1.9 × 1.4 × 8 mm3. An inversion time (TI) scout with increasing TI value was performed on mid ventricular short axis slice to determine the TI that allowed the optimal nulling of normal myocardium before the LGE images were obtained in a stack of LV short axis slices and in 2-, 3- and 4-chamber views.For late gadolinium enhancement (LGE) imaging a phase sensitive inversion recovery (PSIR) gradient echo sequence was performed 8-10 min after the administration 0.15 mmol/kg of gadopentetate dimenglumine . The typical sequence parameters included FOV 360 × 290 mmVolumetric analysis for quantification of LV volumes and ejection fraction was obtained on short axis cine images using commercially available QMASS software . LV volume and mass were normalized to body surface area. Left atrial (LA) volumes were calculated using a biplane area and length method following the formula: 0.85xA1xA2/L, where A1 and A2 were areas measured by planimetry in 2- and 4-chamber views, respectively and L was the length of LA perpendicular to the center of mitral annulus in the 4-chamber plane . The cirTagged images were analyzed using HARP software . LV endocardial and epicardial contours were manually drawn in the first phase, which was then automatically propagated. The degradation of tags was common in diastole. Depending on heart rate and image quality 15 up to 20 phases were analyzable. Manual adjustment of contours was provided when automatic tracking failed. On average, it took at least 15 min for an experienced analyst to process one slice.Software for DENSE analysis was proprietary . The myocardium was defined by placing the guide points on endo- and epicardium in addition to the center of LV cavity and the right ventricular insertion points. Contours were drawn in diastole and automatically propagated to all cardiac phases. Post processing took 2-3 min per slice.FT analyses were performed using the following programs, Tomtec , CIM  and Circle . LV contours were obtained by manually tracing the LV endocardium and epicardium at end diastole followed by automatic propagating contours to all phases . ContourExamples of contours from tagging, DENSE and FT are shown in Fig. Intra- and inter-observer variability was analyzed in ten randomly selected cases for each strain type using all five techniques.p-values were considered to be significant when < 0.05. The analysis was performed using SPSS Statistic software for Windows, Version 22.0 .Continuous variables were presented as mean ± standard deviation (SD) and categorical variables as frequencies and proportions. Paired t-test, intraclass correlation coefficient (ICC) and Bland Altman limits of agreement were used for strain comparisons across techniques. ICC and coefficient of variations were used for inter- and intra-observer agreement analysis. All N = 8) and DENSE (N = 3) images. The possible causes included poor breath-hold, body motion and arrhythmia. Therefore, the final analysis cohort consisted of 87 subjects with ten healthy controls and 77 patients with a cardiomyopathy of diverse etiology (Table n = 17) and 29% (n = 27) had a non-infarct pattern. Regional LV wall motion abnormalities were present in 48% (N = 52) of the images analyzed including those due to left bundle branch block.There were 95 subjects recruited. All had acceptable image quality for FT analysis. However, the suboptimal quality was seen in tagging Additional file 2:Movie S2. tagged imaging of 4-chamber view. (AVI 1414 kb)Additional file 3:Movie S3. DENSE imaging of short axis view with strain vector overlay. (AVI 11479 kb)Additional file 4:Movie S4. DENSE imaging of 4-chamber view with strain vector overlay. (AVI 11479 kb)Additional file 5:Movie S5. bSSFP cine imaging of short axis view with feature tracking contours. (MPG 13596 kb)Additional file 6:Movie S6. bSSFP cine imaging of 4-chamber view with feature tracking contours. (MPG 13596 kb)


Mitral regurgitation in ischemic heart disease (IMR) is a strong predictor of outcome but until now, pathophysiology is not sufficiently understood and treatment is not satisfying. We aimed to systematically evaluate structural and functional mitral valve leaflet and annular characteristics in patients with IMR to determine the differences in geometric and dynamic changes of the MV between significant and mild IMR.Thirty-seven patients with IMR (18 mild (m)MR, 19 significant (moderate+severe) (s)MR) and 33 controls underwent TEE. 3D volumes were analyzed using 3D feature-tracking software.All IMR patients showed a loss of mitral annular motility and non-planarity, whereas mitral annulus dilation and leaflet enlargement occurred in sMR only. Active-posterior-leaflet-area decreased in early systole in all three groups accompanied by an increase in active-anterior-leaflet-area in early systole in controls and mMR but only in late systole in sMR.In addition to a significant enlargement and loss in motility of the MV annulus, patients with significant IMR showed a spatio-temporal alteration of the mitral valve coaptation line due to a delayed increase in active-anterior-leaflet-area. This abnormality is likely to contribute to IMR severity and is worth the evaluation of becoming a parameter for clinical decision-making. Further, addressing the leaflets aiming to increase the active leaflet-area is a promising therapeutic approach for significant IMR. Additional studies with a larger sample size and post-operative assessment are warranted to further validate our findings and help understand the dynamics of the mitral valve. Mitral regurgitation is a strong predictor of cardiac outcome in patients with ischemic heart disease and is associated with higher mortality , 2. The IMR has been subject to detailed investigation using three-dimensional (3D) echocardiography and important changes of the MV apparatus have been found. The mitral annulus has been shown to increase in size, flatten its saddle-like shape and loose its dynamic function with higher degrees of IMR –19. NeveWe analyzed the stored images of 37 consecutive patients with ischemic heart disease, who had a TEE out of clinical reasons. Inclusion criteria were 1) ischemic heart disease shown by cardiac catheterization, 2) mitral regurgitation of any degree and 3) structurally normal mitral valve in comprehensive echocardiographic evaluation. Exclusion criteria were 1) acute myocardial infarction, 2) contraindications to undergoing TEE, 3) structural mitral valve or subvalvular disease , 4) significant regurgitation or stenosis of any other cardiac valve, 5) other cardiac disease. IMR severity was determined according to current guidelines , 21 and TEE was performed according to the American Society of Echocardiography Guidelines  using anBlinded to MR severity, we used custom 3D feature-tracking software  to analyze the datasets. As ECG information is lost when data are exported to the software platform, we identified end-diastole as the first frame when the mitral valve was completely closed and end-systole as the frame preceding mitral valve opening. Initial frame of interest was mid-systole, the mid-frame between end-diastole and end-systole. Mitral annular tracking points were identified in two perpendicular planes in mid-systole. The aortic valve and the apical aortic annulus point were marked and the leaflet coaptation line was defined in a 3-chamber view plane. After defining those landmarks, the program automatically tracked the valve in the initial frame and adjustments of the mitral annulus and the leaflets were performed when necessary Fig. . Subsequp-values < 0.05 were considered statistically significant.Data analysis was performed using Prism6® . Patient characteristics and echocardiography variables are presented as mean ± standard deviation (SD). Inter- and intra-observer variability are expressed as the absolute difference between two measurements as a percentage of their mean values. For categorical variables differences between groups were assessed using Fishers’s exact test. The difference in WMA score between mMR and sMR was calculated using Mann-Whitney Test. For continuous variables differences between groups were analyzed by one-way analysis of co-variance (ANCOVA), and corrected for multiple testing by the Holm-Sidak method. All variables were assessed for normality using the Shapiro-Wilks test, and non-parametric variables were logarithmically transformed prior to analysis. All tests were two-sided, and Table p = 0.042) and annular displacement velocity  vs. 25 mm/s (mMR) and 24 mm/s (sMR), p <  0.0001), as assessed by 3D analysis, were markedly reduced in both IMR groups with no significant differences between both patients groups. Frame rates were similar amongst all three groups.Annular displacement  vs. 5.3 mm (mMR and sMR), Coefficients of variation were low (≤6%) for all diameters, annulus circumference, non-planar angle and annular displacement and velocity, whereas coefficients of variation were higher for annulus area and anterior and posterior leaflet area Table .Table 2IInitial measurements were performed in mid-systole Table . There wThe non-planar angle was significantly flattened in both IMR groups compared to controls with no difference between mMR and sMR patients.The above detailed mid-systolic differences in MV characteristics between IMR groups and controls were present in end-diastole and end-systole, too Table .In controls, we observed an increase in AP diameter, AL-PM diameter, intercommissural diameter, annulus circumference and annulus area which primarily occurred in early systole Table , Fig. 4.The widening of the mitral annulus in early systole occurred in mMR as well, but it occurred later in sMR, which was associated with an increase in anterior leaflet area. A decrease in posterior leaflet area in early systole was seen in all three groups but reached significant values in sMR only.Leaflet tenting volume and height decreased significantly in early systole in all three groups with a slight but insignificant increase in late systole. This was accompanied by flattening of the non-planar angle, which was most obvious in the sMR group.To our knowledge, this is the first study reporting on the structural and functional dynamic modifications of the mitral valve in different grades of IMR, tracked from end-diastole to end-systole, and assessed by high resolution 3D TEE. The main findings of the present investigation were: 1) as compared to controls or patients with mild valve regurgitation, patients with significant IMR have a bidirectional dilated mitral annulus as well as an increase of the active area of both valve leaflets considered in absolute terms. Furthermore, this group of patients shows 2) loss of the normal mitral non-planar saddle shape, and 3) pronounced reduction of the active-posterior-leaflet-area in early systole as well as 4) delayed dynamic augmentation of the active-anterior-leaflet-area.We observed 37 patients with IMR and subdivided them by IMR severity. We pooled patients with moderate and severe IMR into one group  since it is this group for which mitral valve surgery in combination with coronary artery bypass surgery would be considered , 24. By In our study, intra- and interobserver variability for one-dimensional measurements like annular diameters and circumference was excellent and was similar compared to other studies using semi-automated analysis software , 25, 26.Patients with mMR showed no significant differences in anatomical annular parameters  compared to controls, whereas these parameters were significantly larger in sMR. Applying the Pringle Principle, the significant increase in annular circumference and area in absence of difference in planarity in sMR indicates a real dilation of the mitral annulus, not only a change in shape. We further observed smaller absolute and relative intra-systolic changes in annulus area in both IMR groups as correlate for the mitral annulus’ loss of motility, its ability to modify its shape throughout the cardiac cycle , 13, 27,The dilation of the mitral annulus confirms reports of previous studies , 13, 28 Anterior and posterior leaflet areas were significantly larger in sMR compared to controls and mMR. This might be caused by mitral annular enlargement with subsequent augmentation of the leaflets’ circumference but leaflet enlargement also occurs as response to hemodynamic stress and chronic tethering , 13, 29.The active-posterior-leaflet-area (measured in the closed MV from the annulus to the coaptation line) showed a decrease in early systole, non-significant in controls and mMR but significant in sMR, most probably due to tethering. In return, controls had a significant and homogenous increase in active-anterior-leaflet-area throughout systole, which occurred only in late systole in sMR. This systolic relocation of the coaptation zone with a posterior movement of the coaptation line in competent MVs implies an “anterior leaflet reserve” to compensate for the posterior movement , 33. TheOn the one hand, this finding should trigger the proceeding in the development of novel treatment options like surgical elongation of the anterior mitral leaflet  or appliOwing to the study design, we had no consistent information on the onset of coronary artery disease, i.e. the duration of the disease and the dynamic development of IMR and IMR severity. Further, not all patients had a recent angiogram, however, we were able to assess wall motion abnormalities as a surrogate of coronary artery disease in the TEE images. Lastly, the intra- and inter- observer variability for “squared” parameters, which could be an important limitation for common and easily practical application of the software, was higher when compared to “simple” values but still in the range of previous reports .In addition to a significant enlargement and loss in motility of the MV annulus, patients with significant IMR showed a spatio-temporal alteration of the mitral valve coaptation line due to a delayed increase in active-anterior-leaflet-area. This abnormality is likely to contribute to IMR severity and is worth the evaluation of becoming a parameter for clinical decision-making. Further, addressing the leaflets aiming to increase the active leaflet-area is a promising therapeutic approach for significant IMR. Our observations are based on a small but well characterized patient sample and should therefore be regarded hypothesis-generating; studies with a larger sample size and post-operative assessment are warranted to further validate our findings, explore their pathophysiologic etiology, and help understand the dynamics of the mitral valve.