Continuous-flow Mechanical Circulatory Support Research Articles

Post-transplant survival with pre-transplant durable continuous-flow mechanical circulatory support in a Swiss cohort of heart transplant recipients.

Worldwide, almost half of all heart transplantation candidates arrive today at their transplant operation with durable continuous-flow mechanical circulatory support (CF-MCS). This evolution is due to a progressive increase of waiting list time and hence an increased risk of haemodynamic worsening. Longer duration of CF-MCS is associated with a higher risk of device-related complications with potential adverse impact on post-transplant outcome as suggested by recent results from the United Network of Organ Sharing of the United States. A 2-centre Swiss heart transplantation programme conducted a retrospective observational study of consecutive patients of theirs who underwent a transplant in the period 2008-2020. The primary aim was to determine whether post-transplant all-cause mortality is different between heart transplant recipients without or with pre-transplant CF-MCS. The secondary outcome was the acute cellular rejection score within the first year post-transplant. The study participants had a median age of 54 years; 38/158 (24%) were females. 53/158 study participants (34%) had pre-transplant CF-MCS with a median treatment duration of 280 days. In heart transplant recipients with pre-transplant CF-MCS, the prevalence of ischaemic cardiomyopathy was higher (51 vs 32%; p = 0.013), the left ventricular ejection fraction was lower (20 vs 25; p = 0.047) and pulmonary vascular resistance was higher (2.3 vs 2.1 Wood Units; p = 0.047). Over the study period, the proportion of heart transplant recipients with pre-transplant CF-MCS and the duration of pre-transplant CF-MCS treatment increased (2008-2014 vs 2015-2020: 22% vs 45%, p = 0.009; increase of treatment days per year: 34.4 ± 11.2 days, p = 0.003; respectively). The primary and secondary outcomes were not different between heart transplant recipients with pre-transplant CF-MCS or direct heart transplantation (log-rank p = 0.515; 0.16 vs 0.14, respectively; p = 0.81). This data indicates that the strategy of pre-transplant CF-MCS with subsequent orthotopic heart transplantation provides post-transplant outcomes not different to direct heart transplantation despite the fact that the duration of pre-transplant assist device treatment has progressively increased.

Durable Continuous-Flow Mechanical Circulatory Support

The prevalence of heart failure in the UK is 1 in 35 people aged from 65 to 74 and 1 in 15 people aged from 75 to 84 [...]

Impact of continuous-flow mechanical circulatory support on cerebrospinal fluid motility.

Mechanical circulatory support (MCS), including ventricular assist devices (VADs), have emerged as promising therapeutic alternatives for end-stage congestive heart failure (CHF). The latest generation of these devices are continuous flow (CF) blood pumps. While there have been demonstrated benefits to patient outcomes due to CF-MCS, there continue to be significant clinical challenges. Research to-date has concentrated on mitigating thromboembolic risk (stroke), while the downstream impact of CF-MCS on the cerebrospinal fluid (CSF) flow has not been well investigated. Disturbances in the CSF pressure and flow patterns are known to be associated with neurologic impairment and diseased states. Thus, here we seek to develop an understanding of the pathophysiologic consequences of CF-MCS on CSF dynamics. We built and validated a computational framework using lumped parameter modeling of cardiovascular, cerebrovascular physics, CSF dynamics, and autoregulation. A sensitivity analysis was performed to confirm robustness of the modeling framework. Then, we characterized the impact of CF-MCS on the CSF and investigated cardiovascular conditions of healthy and end-stage heart failure. Modeling results demonstrated appropriate hemodynamics and indicated that CSF pressure depends on blood flow pulsatility more than CSF flow. An acute equilibrium between CSF production and absorption was observed in the CF-MCS case, characterized by CSF pressure remaining elevated, and CSF flow rates remaining below healthy, but higher than CHF states. This research has advanced our understanding of the impact of CF-MCS on CSF dynamics and cerebral hemodynamics.

A comprehensive comparison of the in vitro hemocompatibility of extracorporeal centrifugal blood pumps.

Purpose: Blood damage has been associated with patients under temporary continuous-flow mechanical circulatory support. To evaluate the side effects caused by transit blood pumping, in vitro hemocompatibility testing for blood damage in pumps is considered a necessary reference before clinical trials. Methods: The hemocompatibility of five extracorporeal centrifugal blood pumps was investigated comprehensively, including four commercial pumps (the Abbott CentriMag, the Terumo Capiox, the Medos DP3, and the Medtronic BPX-80) and a pump in development (the magAssist MoyoAssist®). In vitro, hemolysis was tested with heparinized porcine blood at nominal operating conditions (5L/min, 160mmHg) and extreme operating conditions (1L/min, 290mmHg) using a circulation flow loop. Hematology analyses concerning the blood cell counts and the degradation of high-molecular-weight von Willebrand factor (VWF) during 6-h circulation were also evaluated. Results: Comparing the in vitro hemocompatibility of blood pumps at different operations, the blood damage was significantly more severe at extreme operating conditions than that at nominal operating conditions. The performance of the five blood pumps was arranged in different orders at these two operating conditions. The results also demonstrated superior hemocompatibility of CentriMag and MoyoAssist® at two operating conditions, with overall low blood damage at hemolysis level, blood cell counts, and degradation of high-molecular-weight VWF. It suggested that magnetic bearings have an advantage in hemocompatibility compared to the mechanical bearing of blood pumps. Conclusion: Involving multiple operating conditions of blood pumps in in vitro hemocompatibility evaluation will be helpful for clinical application. In addition, the magnetically levitated centrifugal blood pump MoyoAssist® shows great potential in the future as it demonstrated good in vitro hemocompatibility.

Artificial Deep Neural Network for Sensorless Pump Flow and Hemodynamics Estimation During Continuous-Flow Mechanical Circulatory Support.

The objective of this study was to compare the estimates of pump flow and systemic vascular resistance (SVR) derived from a mathematical regression model to those from an artificial deep neural network (ADNN). Hemodynamic and pump-related data were generated using both the Cleveland Clinic continuous-flow total artificial heart (CFTAH) and pediatric CFTAH on a mock circulatory loop. An ADNN was trained with generated data, and a mathematical regression model was also generated using the same data. Finally, the absolute error for the actual measured data and each set of estimated data were compared. A strong correlation was observed between the measured flow and the estimated flow using either method (mathematical, R = 0.97, p < 0.01; ADNN, R = 0.99, p < 0.01). The absolute error was smaller in the ADNN estimation (mathematical, 0.3 L/min; ADNN 0.12 L/min; p < 0.01). Furthermore, strong correlation was observed between measured and estimated SVR (mathematical, R = 0.97, p < 0.01; ADNN, R = 0.99, p < 0.01). The absolute error for ADNN estimation was also smaller than that of the mathematical estimation (mathematical, 463 dynes·sec·cm -5 ; ADNN, 123 dynes·sec·cm -5 , p < 0.01). Therefore, in this study, ADNN estimation was more accurate than mathematical regression estimation. http://links.lww.com/ASAIO/A991.

Early Low Pulse Pressure in VA-ECMO Is Associated with Acute Brain Injury.

Pulse pressure is a dynamic marker of cardiovascular function and is often impaired in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Pulsatile blood flow also serves as a regulator of vascular endothelium, and continuous-flow mechanical circulatory support can lead to endothelial dysfunction. We explored the impact of early low pulse pressure on occurrence of acute brain injury (ABI) in VA-ECMO. We conducted a retrospective analysis of adults with VA-ECMO at a tertiary care center between July 2016 and January 2021. Patients underwent standardized multimodal neuromonitoring throughout ECMO support. ABI included intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, cerebral edema, seizure, and brain death. Blood pressures were recorded every 15min. Low pulse pressure was defined as a median pulse pressure < 20mmHg in the first 12h of ECMO. Multivariable logistic regression was performed to investigate the association between pulse pressure and ABI. We analyzed 5138 blood pressure measurements from 123 (median age 63; 63% male) VA-ECMO patients (54% peripheral; 46% central cannulation), of whom 41 (33%) experienced ABI. Individual ABIs were as follows: ischemic stroke (n = 18, 15%), hypoxic ischemic brain injury (n = 14, 11%), seizure (n = 8, 7%), intracranial hemorrhage (n = 7, 6%), cerebral edema (n = 7, 6%), and brain death (n = 2, 2%). Fifty-eight (47%) patients had low pulse pressure. In a multivariable model adjusting for preselected covariates, including cannulation strategy (central vs. peripheral), lactate on ECMO day 1, and left ventricle venting strategy, low pulse pressure was independently associated with ABI (adjusted odds ratio 2.57, 95% confidence interval 1.05-6.24). In a model with the same covariates, every 10-mmHg decrease in pulse pressure was associated with 31% increased odds of ABI (95% confidence interval 1.01-1.68). In a sensitivity analysis model adjusting for systolic pressure, pulse pressure remained significantly associated with ABI. Early low pulse pressure (< 20mmHg) was associated with ABI in VA-ECMO patients. Low pulse pressure may serve as a marker of ABI risk, which necessitates close neuromonitoring for early detection.

Comparative Analyses of Donor-Recipient Age Differences in Adult Cardiothoracic Transplantation: An Analysis of the UNOS/OPTN Database

<h3>Purpose</h3> Broad trends towards increased thoracic organ transplantation in older recipients are well-described. Additionally, usage of older donor organs is well-accepted by many programs. However, little is known about comparative recipient and donor age demographics, and how these may vary with time. <h3>Methods</h3> Using UNOS/OPTN STAR database for both isolated heart (iHTx) and lung transplantation (iLTx) in adults (1988-2017), annual composition of donor organ pool, recipient waitlist pool, and transplanted patient pool, were characterized with respect to age. The 30-day and 1-year recipient survival outcomes are reported. <h3>Results</h3> For iHTx, temporal trends of increased transplantation of older recipients were observed; increased percentages of recipients aged 60-69 and >70 were identified, with decreases in recipients aged 50-59 and 40-49. These trends were identified in iLTx as well, and were more substantial. In both iHTx and iLTx, by 2017, recipients aged 60-69 accounted for the single largest age range undergoing transplantation. However, analysis of survival outcomes from 2010-17 for iHTx (durable continuous flow mechanical circulatory support era), and from 2006-17 for iLTx (lung allocation score era) revealed reduced 30-day and 1-year survival as a function of recipient age, with exception of iLTx in the age 18-29 group. In contrast, no clear temporal trends were observed with respect to donor heart and lung age demographics. Heart and lung donors aged 18-29 accounted for the single largest age range, followed by ages 30-39. <h3>Conclusion</h3> Cardiothoracic transplantation involves a transference of organs from younger to older individuals, and the extent of this has increased more recently. However, older recipients have decreased short-term survival, which likely translates to diminished long-term survival, given a decreased prospective life expectancy even for healthy older individuals. These findings may have implications for organ allocation policies.

Durable Continuous-Flow Mechanical Circulatory Support: State of the Art

Implantable mechanical circulatory support (MCS) systems for ventricular assist device (VAD) therapy have emerged as an important strategy due to a shortage of donor organs for heart transplantation. A growing number of patients are receiving permanent assist devices, while fewer are undergoing heart transplantation (Htx). Continuous-flow (CF) pumps, as devices that can be permanently implanted, show promise for the treatment of both young and old patients with heart failure (HF). Further improvement of these devices will decrease adverse events, enable pulse modulation of continuous blood flow, and improve automatic remote monitoring. Ease of use for patients could also be improved. We herein report on the current state of the art regarding implantable CF pumps for use as MCS systems in the treatment of advanced refractory HF.

Pulseless Paradoxus: A Clue to the Presence of Cardiac Tamponade During Continuous-Flow Mechanical Circulatory Support

This letter to the editor is in response to the published article by by Akhtar et al.

Regulation of Angiopoietin-2 Before and After Mechanical Circulatory Support Therapy.

Gastrointestinal bleeding (GIB) during mechanical circulatory support (MCS) is a major unsolved comorbidity. Inadequate activation of angiopoietin-2-related systems is considered as a major cause of GIB. However, the regulation of angiopoietin-2 remains unknown. Consecutive 20 patients who received continuous-flow MCS therapy (MCS group) and 12 with advanced heart failure (HF; HF group) were prospectively enrolled and their angiopoetin-2 levels were compared. Angiopoietin-2 level had a moderate correlation with log10 B-type natriuretic peptide (BNP; r = 0.39, p < 0.001). The MCS group had significantly higher angiopoietin-2 level divided by log10 BNP compared with the HF group (2.80 ± 0.20 vs. 1.88 ± 0.17, p < 0.001). Angiopoetin-2 had a moderate correlation with central venous pressure and C-reactive protein during the MCS support (r = 0.51 and r = 0.45, respectively). Higher angiopoietin-2 level divided by log10 BNP (> 4.3) was significantly associated with the occurrence of GIB with a hazard ratio of 296 (95% confidence interval 2.24-38620, p = 0.0224). Angiopoietin-2 was already elevated in the HF cohort and more elevated following MCS initiation. Among the MCS cohort, angiopoietin-2 was particularly elevated in patients with systemic congestion and inflammation and was associated with higher incidence of GIB.

Inhibition of adamts13: a novel therapy to treat mechanical circulatory support-induced acquired von willebrand syndrome

Abstract Introduction Bleeding is the most frequent adverse event in patients with continuous flow mechanical circulatory support (CF-MCS) and has been linked to the occurrence of acquired von Willebrand syndrome (aVWS). MCS devices cause an increased shear-induced proteolysis of von Willebrand factor (VWF) by ADAMTS13, leading to aVWS. Hence, specifically blocking ADAMTS13 might be an efficient way to rescue the loss of HMW VWF multimers in CF-MCS patients. Purpose To investigate if blocking ADAMTS13, using an in-house developed inhibitory anti-ADAMTS13 monoclonal antibody (mAb), prevents the loss of high molecular weight (HMW) VWF multimers in in vitro CF-MCS systems and to determine the efficacy of this therapy in a CF-MCS calf model. Methods Human blood was perfused through in vitro CF-MCS systems (Heartmate II and Impella CP, axial flow heart pumps) in the presence of the inhibitory or control mAb (20 μg/mL). Bovine blood was perfused through an in vitro Impella 5.5 system with the inhibitory mAb (20 μg/mL) or PBS. Next, Impella 5.5 pumps were implanted in calves. One dose of the inhibitory mAb (600 μg/kg) or PBS was injected eight days after Impella implantation. Plasma samples were analysed for VWF multimers, VWF antigen (VWF:Ag) and VWF collagen binding activity (VWF:CB). Results A time-dependent decrease in HMW VWF multimers was observed in both in vitro CF-MCS systems in the presence of the control mAb, leading to a 70% reduction of HMW VWF multimers, 180 minutes (min) after blood perfusion (p=0.01 for HM II and p=0.0003 for Impella). This was also reflected by a severely decreased VWF:CB/VWF:Ag ratio (0.59±0.11 and 0.52±0.10 at 180 min versus 1.00±0.06 and 1.07±0.09 before perfusion, for the HM II (p=0.03) and Impella (p=0.001) respectively). Interestingly, blocking ADAMTS13 using the inhibitory mAb prevented the loss of HMW VWF multimers in both systems (p=0.50 for the HM II and p=0.06 for the Impella, 180 min after the start of perfusion). The preservation of HMW VWF multimers was also reflected by normal VWF:CB/VWF:Ag ratios (0.92±0.16 and 0.97±0.11 at 180 min versus 0.93±0.09 and 1.19±0.12 before perfusion for the HM II (p=0.75) and Impella (p=0.06) respectively). Blocking bovine ADAMTS13 using the inhibitory mAb could prevent the loss of HMW VWF multimers in the in vitro Impella 5.5 system, showing that the calf is a good preclinical animal model to study the in vivo effect of this novel therapy. Impella implantation in the calves led to a decrease in HMW VWF multimers (Figure 1A and B). Hence, this animal model represents the VWF laboratory features of MCS-induced aVWS. Moreover, the loss of HMW VWF multimers after pump implantation could be rescued after injection of the inhibitory mAb (Figure 1A and B). Conclusion Blocking ADAMTS13 rescues MCS-induced VWF proteolysis in calves. Hence, inhibiting ADAMTS13 function could become a promising therapeutic strategy to rescue aVWS-induced bleeding in MCS patients. Figure 1. Impella calf model Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Fund for Scientific Research Flanders

A simulation tool for mechanical circulatory support device interaction with diseased states.

We have created a simulation model to investigate the interactions between a variety of mechanical circulatory support (MCS) devices and the circulatory system with various simulated patient conditions and disease states. The present simulation accommodates a family of continuous-flow MCS devices under various stages of consideration or development at our institution. This article describes the mathematical core of the in silico simulation system and shows examples of simulation output imitating various disease states and of selected in vitro and clinical data from the literature.

A review of implantable pulsatile blood pumps: Engineering perspectives.

It has been reported that long-term use of continuous-flow mechanical circulatory support devices (CF-MCSDs) may induce complications associated with diminished pulsatility. Pulsatile-flow mechanical circulatory support devices (PF-MCSDs) have the potential of overcoming these shortcomings with the advance of technology. In order to promote in-depth understanding of PF-MCSD technology and thus encourage future mechanical circulatory support device innovations, engineering perspectives of PF-MCSD systems, including mechanical designs, drive mechanisms, working principles, and implantation strategies, are reviewed in this article. Some emerging designs of PF-MCSDs are introduced, and possible elements for next-generation PF-MCSDs are identified.

148 Inappropriate elevation of angiopoietin-2 relative to hemodynamic stability is associated with bleeding events in patients with continuous flow mechanical circulatory support

Abstract Funding Acknowledgements none Background Elevated angiopoietin-2 (Ang-2) has been attributable to a potential cause of gastrointestinal bleeding among patients with continuous flow (CF) mechanical circulatory support (MCS) in the US, but Ang-2 levels have not been examined in the Japanese MCS patients who are likely to have less gastrointestinal bleeding. Methods We enrolled 18 patients (64 ± 16y; LVEF 26 ± 9%) with advanced heart failure (HF) who received temporary or durable MCS, or were given intravenous inotropes from August 2018 to January 2019. Serum Ang-2 and plasma BNP were simultaneously measured at various treatment status. The relationship between each value and any spontaneous bleeding events requiring hemostasis or blood transfusion was examined. Results 103 blood samples were collected and divided into 2 groups. One was the CF group, which consisted of samples from patients under CF-MCS (Impella, ECMO, Jarvik2000, HeartMateII), and the others were assigned to the Non-CF group. Ang-2 levels had a positive correlation with BNP levels (r = 0.33, p = 0.0006, Fig). CF-MCS efficiently lowered BNP levels (353 ± 125 in CF vs 1053 ± 119 in Non-CF, pg/mL, p &amp;lt; 0.0001), but Ang-2 levels relative to BNP levels were significantly higher in the CF group as shown in the Figure (Ang-2/log10(BNP) ratio: 3.77 ± 0.30 in CF vs 2.43 ± 0.29 in Non-CF, p = 0.0017). Bleeding events were remarkably frequent when Ang-2/log10(BNP)&amp;gt;3.17 (77.8%) than ≦3.17 (22.2%, p = 0.0002). Conclusions High Ang-2 level is normally a marker for hemodynamic compromise, but CF-MCS may stimulate Ang-2 production despite hemodynamic stabilization. Most of spontaneous bleeding events accompany inappropriately high Ang-2 relative to BNP level among Japanese patients with advanced HF. Abstract 148 Figure. Correlation between Ang-2 and BNP

Continuous‐flow mechanical circulatory support is not associated with early graft failure: An analysis of the International Society for Heart and Lung Transplantation registry

Continuous-flow mechanical circulatory support (CF-MCS) is associated with impaired vascular function and increased risk of vasoplegia. One contributing factor to early graft failure (EGF) is severe vasoplegia. We tested the hypothesis that CF-MCS is associated with increased risk of EGF. Adult primary heart transplant recipients in the ISHLT Registry from 2005 to 2013 were stratified into three groups based on pre-transplant MCS: No MCS (n=11748), pulsatile (P)-MCS (n=718), and CF-MCS (n=3818). EGF was defined as death/retransplantation due to graft failure within 30days after HT. Comparisons were made using descriptive statistics and associations. EGF was assessed with multivariable Cox proportional hazard regression. The incidence of EGF within 30days was similar between groups (No MCS 2.2%, P-MCS 3.3%, CF-MCS 2.1%, P=.10). Following multivariable adjustment, the risk of EGF was not statistically different for those with CF-MCS compared with P-MCS (HR 0.75, 95% CI 0.46-1.21, P=.24). The risk of EGF was numerically, but not statistically significantly higher for CF-MCS compared with No MCS (HR 1.24, 95% CI 0.92-1.67, P=.16). CF-MCS use was not associated with a statistically significant increased risk of EGF resulting in death or retransplantation in the first 30days after transplant.

Haemodynamic evaluation of the new pulsatile-flow generation method in vitro.

Continuous-flow ventricular-assist devices are widely used to support patients with advanced heart failure, because continuous-flow ventricular-assist devices are more durable, have smaller sizes and have better survival rates for patients compared to the pulsatile-flow ventricular-assist devices. Nevertheless, continuous-flow ventricular-assist devices often cause complications such as gastrointestinal bleeding, haemorrhagic stroke, and aortic insufficiency and have a negative impact on the microcirculation for both long-time implantable and short-time extracorporeal systems. The aim of this study is the evaluation of the pulsatile-flow generation method in continuous-flow ventricular-assist device without pump speed changes. The method may be used for short-time extracorporeal continuous-flow mechanical circulatory support and long-time implantable mechanical circulatory support. A shunt with a controlled adjustable valve, that clamps periodically, is connected in parallel to the continuous-flow ventricular-assist device. We compared the continuous-flow ventricular-assist device operating with and without the shunt on the mock circulation loop. The continuous-flow ventricular-assist device-shunt system was connected according to the left ventricle-aorta circuit and worked in phase with the ventricle. Heart failure was simulated on the mock circulation circuit. Rotaflow (Maquet Inc.) was used as the continuous-flow pump. Haemolysis studies of the system for generating a pulse flow were carried out at a flow rate of 5 L/min and a pressure drop of 100 mm Hg. To compare the haemodynamic efficiency, we used the aortic pulsation index Ip, the equivalent energy pressure and the surplus haemodynamic energy. These indexes were higher in the pulsatile mode (Ip - 4 times, equivalent energy pressure by 7.36% and surplus haemodynamic energy - 10 times), while haemolysis was the same. The normalised index of haemolysis was 0.0015 ± 0.001. The results demonstrate the efficiency of the pulsatile-flow generation method for continuous-flow ventricular-assist devices without impeller rotation rate changes.

Continuous-flow mechanical circulatory support induces shedding of platelet adhesion receptors GpIb and GpVI

Hemorrhagic complications, especially mucosal bleedings, are very common for using continuous-flow mechanical circulatory supports (CF-MCS) including Extracorporeal Membrane Oxygenation (ECMO). CF-MCS could impact platelets by exposing this key player in primary hemostasis to high shear stress. A proteolytic cleavage (shedding) of platelet adhesion receptors GpIb and GpVI has been described under high shear stress and could contribute to the hemorrhagic complications in patients with CF-MCS. To assess whether CF-MCS promotes GpIb and GpVI shedding in vitro and in vivo and determine the kinetic evolution during the CF-MCS. First platelet shedding was investigated in vitro using a CF-MCS (Impella-CP®, Abiomed) loop model. Plasma with normal platelet count (plasma-NPC) was obtained by dilution of platelet-rich plasma collected from healthy donors in fresh frozen plasma. Sampling was performed before and after 2, 5, 30, 60 and 180 min perfusion of plasma-NPC in the loop model ( n = 4 runs). Platelet shedding was also investigated for the blood samples collected from 20 ECMO patients (WITECMO-h trial). Platelets of 20 healthy volunteers were evaluated as a control. GpIbα and GpVI shedding was analyzed by flow cytometry. A significant time-dependent decrease of GpIbα ( P < 0.001) and GpVI ( P < 0.001) MFI was observed after 180 min in the Impella®-CP loop model. In vivo baseline GpIbα and GpVI MFIs has been significantly decreased before ECMO implantation compared to the healthy subjects ( P < 0.001). After ECMO implantation, no significant variation of GpIbα and GpVI MFI was observed. CF-MCS induces platelet GpIb and GpVI shedding in vitro. Increased GpIb and GpVI shedding is already present before ECMO implantation and remain significantly elevated after the implantation. Loss of the platelet receptors GPIbα and GPVI in patients with CF-MCS may contribute to hemorrhagic complications observed in these patients.

Effect of Continuous-Flow Mechanical Circulatory Support on Microvasculature Remodeling in the Failing Heart.

Left ventricle (LV) unloading caused by a left ventricular assist device (LVAD) has been shown to enhance reverse LV remodeling in end-stage cardiomyopathy. Several reports consistently suggest that a pulsatile-flow LVAD has more profound effects compared to continuous-flow LVAD, though the responsible mechanisms are not fully understood. We hypothesized that arterial pulsatility, being affected by the type of LVAD, may affect microvasculature and functional/pathological LV remodeling in end-stage cardiomyopathy. The study included 18 patients with chronic heart failure who underwent LVAD implantation. Eight patients were implanted with pulsatile-flow LVAD, and 10 patients were implanted with continuous-flow LVAD. The results of serial echocardiograms and histopathological assessment of transmural LV tissues, which were collected during the implantation and removal of LVADs, were compared between the groups. The results of echocardiography showed that LV systolic dimension and LV ejection fraction improved greatly in the pulsatile-flow LVAD group compared to the continuous-flow LVAD group. Histological analysis showed that in both groups, increased microvasculature density and decreased cardiomyocyte size during LVAD support had no significant difference. In contrast, only the patients with continuous-flow LVADs had presented with significant increase in α-smooth muscle actin (α-SMA)-positive layer thickness and the number of proliferating cell nuclear antigen (PCNA)-positive cells of myocardial arterioles. We concluded that the use of long-term continuous-flow LVAD support, having less pulsatility, had induced more thickening to the medial layer of myocardial arterioles compared to the use of pulsatile-flow LVADs. Our findings suggest that the pathological impairment of myocardial microvascular structure during continuous-flow LVAD support may be a novel mechanism which accounts for the difference in LV remodeling depending on the type of LVAD.

Calculation of the ALMA Risk of Right Ventricular Failure After Left Ventricular Assist Device Implantation.

Right ventricular failure after continuous-flow left ventricular assist device (LVAD) implantation is still an unsolved issue and remains a life-threatening event for patients. We undertook this study to determine predictors of the patients who are candidates for isolated LVAD therapy as opposed to biventricular support (BVAD). We reviewed demographic, echocardiographic, hemodynamic, and laboratory variables for 258 patients who underwent both isolated LVAD implantation and unplanned BVAD because of early right ventricular failure after LVAD insertion, between 2006 and 2017 (LVAD = 170 and BVAD = 88). The final study patients were randomly divided into derivation (79.8%, n = 206) and validation (20.1%, n = 52) cohorts. Fifty-seven preoperative risk factors were compared between patients who were successfully managed with an LVAD and those who required a BVAD. Nineteen variables demonstrated statistical significance on univariable analysis. Multivariable logistic regression analysis identified destination therapy (odds ratio [OR] 2.0 [1.7-3.9], p = 0.003), a pulmonary artery pulsatility index <2 (OR 3.3 [1.7-6.1], p = 0.001), a right ventricle/left ventricle end-diastolic diameter ratio >0.75 (OR 2.7 [1.5-5.5], p = 0.001), an right ventricle stroke work index <300 mm Hg/ml/m (OR 4.3 [2.5-7.3], p < 0.001), and a United Network for Organ Sharing modified Model for End-Stage Liver Disease Excluding INR score >17 (OR 3.5 [1.9-6.9], p < 0.001) as the major predictors of the need for BVAD. Using these data, we propose a simple risk calculator to determine the suitability of patients for isolated LVAD support in the era of continuous-flow mechanical circulatory support devices.

Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support

BackgroundThe main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied. ObjectivesThe purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS. MethodsWe assessed the effect of 2 CF-MCS on VWF multimer degradation in a mock circulatory loop (model 1). Using these devices, we investigated in a dose-effect model (model 2) 3 levels of pulsatility in 3 groups of swine. In a cross-over model (model 3), we studied the effects of sequential changes of pulsatility on VWF. We reported the evolution of VWF multimerization in a patient undergoing serial CF-MCS and/or pulsatile-MCS. ResultsWe demonstrated the proteolytic degradation of VWF multimers by high shear CF-MCS in a circulatory loop without pulsatility. We observed both in swine models and in a patient that the magnitude of the VWF degradation is modulated by the pulsatility level in the high shear-stress level condition, and that the restoration of pulsatility is a trigger for the endothelial release of VWF. ConclusionsWe demonstrated that the VWF defect reflects the balance between degradation induced by the shear stress and the endothelial release of new VWF triggered by the pulsatility. This modulation of VWF levels could explain the relationship between pulsatility and bleeding observed in CF-MCS recipients. Preservation of pulsatility may be a new target to improve clinical outcomes of patients.