Early intervention for lactate dehydrogenase elevation improves clinical outcomes in patients with the HeartMate II left ventricular assist device: Insights from the PREVENT study

BACKGROUND: Hemolysis, assessed by elevated serum lactate dehydrogenase (LDH), is strongly associated with HeartMate II pump thrombosis (PT). However, it is unknown whether early intervention for elevated LDH circumvents the risk of serious PT requiring pump exchange. We sought to evaluate the relationship between elevated LDH and clinical outcomes, the effectiveness of early medical intervention, and risk factors for elevated LDH. METHODS: We studied 268 patients in the prospective, multicenter PREVENT study who had 2 or more LDH measurements at ≥30 days post-implant. Elevated LDH was defined as LDH ≥2.5× upper limit of normal (ULN) for 2 consecutive measurements. RESULTS: Fourteen percent of patients had elevated LDH. Stroke-free survival at 6 months was lower in patients with elevated LDH vs patients with normal LDH (83 ± 6% vs 93 ± 2%, p = 0.035). Elevated LDH resolved without intervention in 19% of patients, with intensified medical therapy in 43% and required surgical intervention in 38%. For patients receiving only medical therapy, survival was 94 ± 6% at 6 months post-treatment. In this subgroup, resolution of symptoms with intensified medical therapy was sustained in 15 of 16 patients, with PT occurring in 1 patient at 171 days after initial treatment for elevated LDH (202 days post-implant). Early medical intervention at moderately elevated LDH (2.5× to 3.2× ULN), as compared with higher levels (>3.2× ULN), led to more sustained resolution of symptoms without subsequent PT or need for surgical intervention (91% vs 26% at 6 months post-treatment, p = 0.002). CONCLUSIONS: Early medical intervention can successfully resolve moderate LDH elevations (2.5× to 3.2× ULN) with a low incidence of death or PT at 6 months post-treatment

From Benchtop to Beside: Patient-specific Outcomes Explained by Invitro Experiment

Study: Recent analyses show that females have higher early postoperative (PO) mortality and right ventricular failure (RVF) than males after left ventricular assist device (LVAD) implantation; and that this association is partially mediated by smaller LV size in females. Benchtop experiments allow us to investigate patient-specific (PS) characteristics in a reproducible way given the fact that the PS anatomy and physiology is mimicked accurately. With multiple heart models of varying LV size, we can directly study the individual effects of titrating the LVAD speed and the resulting bi-ventricular volumes, shedding light on the interplay between LV and RV as well as resulting inter-ventricular septum (IVS) positions, which may cause the different outcomes pertaining to sex. Methods: In vitro, we studied the impact of the heart size to IVS position using two smaller and two larger sized PS silicone heart phantoms derived from clinical CT images (Fig. 1A). With ultrasound crystals that were integrated on a placeholder inflow cannula, the IVS position was measured during LV and RV volume changes (dV) mimicking varying ventricular loading states (Fig. 1B). Figure 1 A Two small (blue) and two large PS heart phantoms (orange) on B benchtop. C Median septum curvature results. LVEDD/LVV/RVV: LV enddiastolic diameter/LV and RV volume. Results: Going from small to large dV, at zero curvature, the septum starts to shift towards the left; for smaller hearts at dV = -40 mL and for larger hearts at dV = -50 mL (Fig. 1C). This result indicates that smaller hearts are more prone to an IVS shift to the left than larger hearts. We conclude that smaller LV size may therefore mediate increased early PO LVAD mortality and RVF observed in females compared to males. Novel 3D silicone printing technology enables us to study accurate, PS heart models across a heterogeneous patient population. PS relationships can be studied simultaneously to clinical assessments and support the decision-making prior to LVAD implantation

Extracorporeal membrane oxygenation(ECMO) in refractory cardiogenic shock: impact of acute versus chronic etiology on outcome

Refractory cardiogenic shock (CS) is a condition that continues to have a very high mortality despite advances in medical therapy. Conventional treatment typically comprises inotrope infusions, vasopressors and intra-aortic-balloon-pump (IABP). When circulatory instability is refractory to these treatments, mechanical circulatory support represents the only hope for survival, as indicated by current guidelines. As most of these patients present with critical circulatory instability requiring urgent or emergent therapy, the chosen mechanical assistance should be rapidly and easily implanted. For this reason ExtraCorporeal Membrane Oxygenation (ECMO) represents the ideal “bridge-to-life” and increasingly it is used to keep the patient alive while the optimal therapeutic management is determined (bridge-to-decision). Management may then follow one of three courses: “bridge-to-recovery”: patient recovery, and weaning from ECMO; “bridge-to-transplant”: direct heart transplantation; “bridge-to-bridge”: placement of ventricular-assist-device or total artificial longer-term support. There have been several large reports on the use of ECMO as a mechanical support in post-cardiotomy patients but relatively few, mostly small case-series focusing on its role in primary acute cardiogenic shock outside of the post-cardiotomy setting. We present the results of our centre’s experience (Padova) in the treatment of primary acute cardiogenic shock with the PLS-Quadrox ECMO system (Maquet) as a bridge to decision. Furthermore, we evaluated the impact of etiology on patient outcomes by comparing acute primary refractory CS secondary to acute myocardial infarction (AMI), myocarditis, pulmonary embolism (PE) and post-partum cardiomyopathy (PPCM) with acute decompensation of a chronic cardiomyopathy, including dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM) and grown-up-congenital-heart-diseases (GUCHD). We also analyzed whether duration and magnitude of support may predict weaning and survival. Materials and Methods. Between January 2009 and March 2013, we implanted a total of 249 ECMO; in this study we focused on 64 patients where peripheral ECMO was the treatment for primary cardiogenic shock. Thirty-seven cases (58%) were “acute” (Group A-PCS: mostly acute myocardial infarction, 39%), while twenty-seven (42%) had an exacerbation of “chronic” heart failure (Group C-PCS: dilated cardiomyopathy 30%, post-ischemic cardiomyopathy 9%, congenital 3%). Results. In group C-PCS, 23 patients were bridged to a LVAD (52%) or heart transplantation (33%). In group A-PCS, ECMO was used as bridge-to-transplantation in 3 patients (8%), bridge-to-bridge in 9 (24%), and bridge-to-recovery in 18 patients (49%). One patient in both groups was bridged to conventional surgery. Recovery of cardiac function was achieved only in group A-PCS (18 vs 0 pts, p=0.0001). Mean-flow during support ≤60% of the theoretical flow (BSA*2.4) was a predictor of successful weaning (p=0.02). Average duration of ECMO support was 8.9 ±9 days. Nine patients (14%) died during support; 30-day overall survival was 80% (51/64 pts); 59% of patients were discharged, in whom survival at 48 months was 90%. Better survival was observed in patients supported for 8 days or less (74% vs 36%, p=0.002). Conclusions. In “chronic” heart-failure ECMO represents a bridge to VAD or heart-transplantation, while in “acute” settings it offers a considerable chance of recovery, often representing the only required therapy

VAD in failing Fontan: simulation of ventricular, cavo-pulmonary and biventricular assistance in systolic/diastolic ventricular dysfunction and in pulmonary vascular resistance increase.

Aim: Due to the lack of donors, VADs could be an alternative to heart transplantation for Failing Fontan patients (PTs). Considering the complex physiopathology and the type of VAD connection, a numerical model (NM) could be useful to support clinical decisions. The aim of this work is to test a NM simulating the VADs effects on failing Fontan for systolic dysfunction (SD), diastolic dysfunction (DD) and pulmonary vascular resistance increase (PRI). Methods: Data of 10 Fontan PTs were used to simulate the PTs baseline using a dedicated NM. Then, for each PTs a SD, a DD and a PRI were simulated. Finally, for each PT and for each pathology, the VADs implantation was simulated. Results: NM can well reproduce PTs baseline. In the case of SD, LVAD increases the cardiac output (CO) (35%) and the arterial systemic pressure (ASP) (25%). With cavo-pulmonary assistance (RVAD) a decrease of inferior vena cava pressure (IVCP) (39%) was observed with 34% increase of CO. With the BIVAD an increase of ASP (29%) and CO (37%) was observed. In the case of DD, the LVAD increases CO (42%), the RVAD decreases the IVCP. In the case of PRI, the highest CO (50%) and ASP (28%) increase is obtained with an RVAD together with the highest decrease of IVCP (53%). Conclusions: The use of NM could be helpful in this innovative field to evaluate the VADs implantation effects on specific PT to support PT and VAD selection