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Iron deficiency (ID) is a common comorbidity in heart failure (HF). In these patients, intravenous iron administration can improve clinical outcomes and quality of life (QoL). However, data on ID are lacking in patients who have transitioned toward left ventricular assist device (LVAD) or heart transplantation (HTx). All patients who underwent LVAD (n = 84) surgery or HTx (n = 67) at our center between 2012 and 2019, aged ≥18 years with a follow-up of ≥3 months, were included. Retrospectively, the prevalence of ID up to 1 year preoperatively, and up to February 2020 postoperatively, as well as all iron administrations were assessed during this period. Iron status was assessed in 61% and 51% of the LVAD and HTx patients preoperatively, and 81% and 84%, respectively, postoperatively. Of these patients, 53% and 71% of the LVAD and HTx patients preoperatively were diagnosed with ID preoperatively, and 71% and 77%, respectively, postoperatively. ID was more frequently diagnosed >3 months postoperatively. Sixty-three percent of the LVAD (mostly intravenous) and 63% of the HTx patients (mostly oral) received iron administration. ID is highly prevalent pre- and post-LVAD and HTx. It is plausible that substitution can have similar QoL gains as in regular HF patients.

Background: Significant aortic regurgitation at the time of left ventricular assist device (LVAD) implantation, requires concomitant aortic valve (AoV) replacement or repair. However, the impact of concomitant AoV surgery on morbidity remains unknown. Therefore, our aim is to determine the impact of concomitant AoV surgery on thromboembolic and bleeding events. Methods: A retrospective IMACS registry study, including patients implanted from 2013 until September 2017. Differences between different concomitant AoV surgery modalities were analyzed. Results: In total, 785 (5.1%) out of 15.267 patients (median age 58 IQR 49-66 years, 79% male) underwent concomitant AoV surgery (median age 63 IQR 54-69 years, 84% male); 386 (49%) patients received biological prostheses, 71 (9%) mechanical prostheses and 328 (42%) AoV repairs. In total, 54 (8%) patients with AoV surgery experienced a thromboembolic event and 1016 (9%) patients with no AoV surgery. Only AoV repair surgery was associated with an increased rate of pump thrombosis (p=0.024). Furthermore, concomitant AoV surgery was associated with an increased rate of all and nonsurgical bleedings. Following a multivariable Cox regression, concomitant AoV surgery remained an independent predictor for bleeding events. Conclusions: In LVAD patients undergoing concomitant AoV surgery, thromboembolic event rates were not higher, however both all and nonsurgical bleeding event rates were higher. Furthermore, concomitant AoV repair surgery was associated with an increased rate of pump thrombosis.

The updated listing criteria for heart transplantation are presented on behalf of the three heart transplant centres in the Netherlands. Given the shortage of donor hearts, selection of those patients who may expect to have the greatest benefit from a scarce societal resource in terms of life expectancy and quality of life is inevitable. The indication for heart transplantation includes end-stage heart disease not remediable by more conservative measures, accompanied by severe physical limitation while on optimal medical therapy, including ICD/CRT‑D. Assessment of this condition requires cardiopulmonary stress testing, prognostic stratification and invasive haemodynamic measurements. Timely referral to a tertiary centre is essential for an optimal outcome. Chronic mechanical circulatory support is being used more and more as an alternative to heart transplantation and to bridge the progressively longer waiting time for heart transplantation and, thus, has become an important treatment option for patients with advanced heart failure. Supplementary Information The online version of this article (10.1007/s12471-021-01627-x) contains supplementary material, which is available to authorized users.

Summary Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease that affects long‐term outcomes in heart transplant (HTx) patients. We prospectively evaluated the feasibility of coronary computed tomography angiography (CCTA) for the detection of CAV during clinical implementation at our center. All consecutive HTx patients >4 years post‐transplant were actively converted from myocardial perfusion imaging to CCTA for the annual assessment of CAV. Between February 2018 and May 2019, 129/172 (75%) HTx patients underwent a CCTA. Renal impairment (n = 21/43) was the most frequent reason for patients could not undergo CCTA. CCTA image quality was good–excellent in 118/129 (92%) patients, and the radiation dose was 2.1 (1.6–2.8) mSv. CCTA showed obstructive CAV in 19/129 (15%) patients. Thirteen (10%) patients underwent additional tests, of which 8 patients underwent coronary revascularization within 90 days of CCTA. After 1 year, 3 additional coronary angiograms were performed, resulting in one revascularization in a patient with known severe CAV who developed ventricular tachycardia. One myocardial infarction after coronary stenting and 2 non‐cardiac deaths were observed. CCTA can be successfully implemented for routine detection of CAV with good image quality and low radiation dose. CCTA allows CAV evaluation with the limited need for additional invasive testing., CCTA can be safely and successfully implemented as a noninvasive alternative for routine detection of CAV in HTx patients with good image quality and low radiation dose.

OBJECTIVES Driveline infections continue to be a significant complication following left ventricular assist device (LVAD) implantation. Driveline exit-site care is crucial for the prevention of infections; however, there are no uniform guidelines. The goal of this study was to provide an overview of the currently published driveline exit-site care protocols in patients with LVAD. METHODS A systematic literature review was performed. Studies before 15 December 2020 were included if the number of driveline infections was a primary outcome and the driveline exit-site care protocol was explained. RESULTS Eleven articles were included in the systematic review, including 1602 patients with LVADs. The median of the frequency of driveline infections in the articles was 13.8% with a range of 0–52.6%. There was a marked variability in the methods of care of driveline exit sites, without a standardized driveline dressing technique in patients with LVADs. The frequency of driveline infections was 6–7.5% in studies using a dressing kit that included chlorhexidine, a silver-based dressing and an anchoring device. Furthermore, there was variability in the anchoring devices and the frequency of dressing changes, which varied from daily to weekly. No specific anchoring device or change frequency was found to be superior. CONCLUSIONS Based on this systematic review, driveline exit care protocols that included chlorhexidine, a silver-based dressing, the use of an anchoring device and dressing kits might be best in reducing driveline infection rates. However, prospective studies with larger cohorts are needed to establish the optimal protocol for driveline exit-site care.

Background: There is a clinical need for additional remote tools to improve left ventricular assist device (LVAD) patient management. The aim of this pilot concept study was to assess the safety and feasibility of optimizing patient management with add-on remote hemodynamic monitoring using the CardioMEMS in LVAD patients during different treatment stages. Methods: Ten consecutive patients accepted and clinically ready for (semi-) elective HeartMate 3 LVAD surgery were included. All patients received a CardioMEMS to optimize filling pressure before surgery. Patients were categorized into those with normal mean pulmonary artery pressure (mPAP) (≤25 mmHg, n = 4) or elevated mPAP (>25 mmHg, n = 6), and compared to a historical cohort (n = 20). Endpoints were CardioMEMS device safety and a combined endpoint of all-cause mortality, acute kidney injury, renal replacement therapy and/or right ventricular failure at 1-year follow-up. Additionally, we investigated hospital-free survival and improvement in quality of life (QoL) and exercise tolerance. Results: No safety issues or signal interferences were observed. The combined endpoint occurred in 60% of historical controls, 0% in normal and 83% in elevated mPAP group. Post-discharge, the hospital-free survival was significantly better, and the QoL improved more in the normal compared to the elevated mPAP group. Conclusion: Remote hemodynamic monitoring in LVAD patients is safe and feasible with the CardioMEMS, which could be used to identify patients at elevated risk of complications as well as optimize patient management remotely during the out-patient phase with less frequent hospitalizations. Larger pivotal studies are warranted to test the hypothesis generated from this concept study.

Aims: This study aimed to investigate the left ventricular (LV) remodelling and long-term prognosis of patients with new-onset acute heart failure (HF) with reduced ejection fraction who were pharmacologically managed and survived until hospital discharge. We compared patients with ischaemic and non-ischaemic aetiology. Methods and results: This cohort study consisted of 111 patients admitted with new-onset acute HF in the period 2008–2016 [62% non-ischaemic aetiology, 48% supported by inotropes, vasopressors, or short-term mechanical circulatory devices, and left ventricular ejection fraction (LVEF) at discharge 28% (interquartile range 22–34)]. LV dimensions, LVEF, and mitral valve regurgitation were used as markers for LV remodelling during up to 3 years of follow-up. Both patients with non-ischaemic and ischaemic HF had significant improvement in LVEF (P

Aim: We aimed to assess the safety and feasibility of using CardioMEMS monitoring in patients before and after left ventricular assist device (LVAD) surgery. Patients & methods: Ten patients accepted for elective LVAD surgery were included, received a CardioMEMS at baseline and were categorized based on mean pulmonary artery pressure (mPAP) ≤25 mmHg (n = 4) or mPAP >25 mmHg [n = 6]) before LVAD surgery. Results: The combined end point of all-cause mortality, acute kidney injury and/or renal replacement therapy, and right ventricular failure occurred more often in patients with an mPAP >25 mmHg (83 vs 0%, p = 0.017). Conclusion: This pilot study demonstrates that combining CardioMEMS monitoring with LVAD therapy is safe and generates the hypothesis that patients with an mPAP >25 mmHg before LVAD surgery identify a very high-risk group for adverse clinical outcomes.

Introduction: Cardiac resynchronization defibrillator (CRT-D) as primary prevention is known to reduce mortality. At the time of replacement, higher age and comorbidities may attenuate the benefit of implantable cardioverter-defibrillator (ICD) therapy. The purpose of this study was to evaluate the progression of comorbidities after implantation and their association with mortality following CRT-D generator replacement. In addition, a risk score was developed to identify patients at high risk for mortality after replacement. Methods and Results: We identified patients implanted with a primary prevention CRT-D (n = 648) who subsequently underwent elective generator replacement (n = 218) from two prospective ICD registries. The cohort consisted of 218 patients (median age: 70 years, male gender: 73%, mean left ventricular ejection fraction [LVEF]: 36 ± 11% at replacement). Median follow-up after the replacement was 4.2 years during which 64 patients (29%) died and 11 patients (5%) received appropriate ICD shocks. An increase in comorbidities was observed in 77 patients (35%). The 5-year mortality rate was 41% in patients with ≥2 comorbidities at the time of replacement. A risk score incorporating age, gender, LVEF, atrial fibrillation, anemia, chronic kidney disease, and history of appropriate ICD shocks at time of replacement accurately predicted 5-year mortality (C-statistic 0.829). Patients with a risk score of greater than 2.5 had excess mortality at 5-year postreplacement compared with patients with a risk score less than 1.5 (57% vs. 6%; p Conclusion: A simple risk score accurately predicts 5-year mortality after replacement in CRT-D patients, as patients with a risk score of greater than 2.5 are at high risk of dying despite ICD protection.

OBJECTIVES Data on the impact and course of uncorrected tricuspid regurgitation (TR) during left ventricular assist device (LVAD) implantation are scarce and inconsistent. This study explores the clinical impact and natural course of uncorrected TR in patients after LVAD implantation. METHODS The European Registry for Patients with Mechanical Circulatory Support was used to identify adult patients with LVAD implants without concomitant tricuspid valve surgery. A mediation model was developed to assess the association of TR with 30-day mortality via other risk factors. Generalized mixed models were used to model the course of post-LVAD TR. Joint models were used to perform sensitivity analyses. RESULTS A total of 2496 procedures were included (median age: 56 years; men: 83%). TR was not directly associated with higher 30-day mortality, but mediation analyses suggested an indirect association via preoperative elevated right atrial pressure and creatinine (P = 0.035) and bilirubin (P = 0.027) levels. Post-LVAD TR was also associated with increased late mortality [hazard ratio 1.16 (1.06–1.3); P = 0.001]. On average, uncorrected TR diminished after LVAD implantation. The probability of having moderate-to-severe TR immediately after an implant in patients with none-to-mild TR pre-LVAD was 10%; in patients with moderate-to-severe TR pre-LVAD, it was 35% and continued to decrease in patients with moderate-to-severe TR pre-LVAD, regardless of pre-LVAD right ventricular failure or pulmonary hypertension. CONCLUSIONS Uncorrected TR pre-LVAD and post-LVAD is associated with increased early and late mortality. Nevertheless, on average, TR diminishes progressively without intervention after an LVAD implant. Therefore, these data suggest that patient selection for concomitant tricuspid valve surgery should not be based solely on TR grade.

Background The severity of COVID-19 after SARS-CoV-2 infection is unpredictable. Angiotensin-converting enzyme-2 (ACE2) is the receptor responsible for coronavirus binding, while subsequent cell entry relies on priming by the serine protease TMPRSS2 (transmembrane protease, serine 2). Although renin-angiotensin-aldosterone-system (RAAS) blockers have been suggested to upregulate ACE2, their use in COVID-19 patients is now considered safe. The aim of our study was to investigate parameters that determine COVID-19 severity, focusing on RAAS-components and variation in the genes encoding for ACE2 and TMPRSS2.MethodsAdult patients hospitalized due to SARS-CoV-2 infection between May 2020 and October 2020 in the Haga Teaching Hospital were included, and soluble ACE2 (sACE2), renin, aldosterone (in heparin plasma), and polymorphisms in the ACE2 and TMPRSS2 genes (in DNA obtained from EDTA blood) were determined. Measurements and main resultsOf the 188 patients that were included, 60 were defined as severe COVID-19 (ICU and/or death). These patients more often used antidiabetic drugs, were older, had higher renin and sACE2 levels, lower aldosterone levels, and a lower aldosterone/renin ratio. In addition, they displayed the TMPRSS2-rs2070788 AA genotype less frequently. No ACE2 polymorphism-related differences were observed. Multivariate regression analysis revealed independent significance for age, sACE2, the aldosterone/renin ratio, and the TMPRSS2 rs2070788 non-AA genotype as predictors of COVID-19 severity, together yielding a C-index of 0.79. Findings were independent of the use of RAAS blockers. Conclusion High sACE2, a low aldosterone/renin ration, and having the TMPRSS2 rs2070788 non-AA genotype are novel independent determinants that may help to predict COVID-19 disease severity. Trial registration: retrospectively registered

Aims The aim of this study was to compare early- and late-term survival and causes of death between patients with and without a concomitant aortic valve (AoV) procedure during continuous-flow left ventricular assist device (LVAD) surgery. Methods and results All adult primary continuous-flow LVAD patients on the International Society of Heart and Lung Transplantation (ISHLT) Mechanically Assisted Circulatory Support (IMACS) Registry (n = 15 267) were included in this analysis and stratified into patients submitted to a concomitant AoV procedure (AoV replacement or AoV repair) and patients without an AoV procedure. The primary outcome was early (≤90 days) survival post-LVAD surgery. Secondary outcomes were late survival (survival during the entire follow-up period) and conditional survival (in patients who survived the first 90 days post-LVAD surgery), and determinants. Patients who underwent concomitant AoV replacement (n = 457) had significantly reduced late survival compared with patients with AoV repair (n = 328) or without an AoV procedure (n = 14 482) (56% vs. 61% and 62%, respectively; P = 0.001). After adjustment for other significant predictors, concomitant AoV replacement remained an independent predictor for early [hazard ratio (HR) 1.226, 95% confidence interval (CI) 1.037–1.449] and late (HR 1.477, 95% CI 1.154–1.890) mortality. However, patients undergoing AoV replacement or repair, in whom the presence of moderate-to-severe AoV regurgitation was diagnosed prior to LVAD implantation, had survival similar to patients not undergoing AoV interventions. Conclusions Concomitant AoV surgery in patients undergoing LVAD implantation is an independent predictor of mortality. Additional research is needed to determine the best AoV surgical strategy at the time of LVAD surgery.

Background Solid organ transplant (SOT) recipients may be at risk for severe COVID‐19. Data on the clinical course of COVID‐19 in immunosuppressed patients are limited and the effective treatment strategy for these patients is unknown. Methods We describe our institutional experience with COVID‐19 in SOT. Demographic, clinical and treatment data were extracted from the electronic patient files. Results A total of 23 SOT transplant recipients suffering from COVID‐19 were identified (n = 3 heart; n =15 kidney; n = 1 kidney‐after‐heart; n = 3 lung and n = 1 liver transplant recipient). The presenting symptoms were similar to non‐immunocompromised patients Eighty‐three percent (19/23) of the patients required hospitalization but only two of these were transferred to the intensive care unit. Five patients died from COVID‐19; all had high Clinical Frailty scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only 3 patients were treated with chloroquine. Most patients recovered without experimental anti‐viral therapy. Conclusions Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID‐19. Pre‐existent frailty is associated with death from COVID‐19.

Background: Many patients undergoing durable left ventricular assist device (LVAD) implantation suffer from chronic kidney disease (CKD). Therefore, we investigated the effect of LVAD support on CKD. Methods: A retrospective multicenter cohort study, including all patients undergoing LVAD (HeartMate II (n = 330), HeartMate 3 (n = 22) and HeartWare (n = 48) implantation. In total, 227 (56.8%) patients were implanted as bridge-to-transplantation; 154 (38.5%) as destination therapy; and 19 (4.7%) as bridge-to-decision. Serum creatinine measurements were collected over a 2-year follow-up period. Patients were stratified based on CKD stage. Results: Overall, 400 patients (mean age 53 ± 14 years, 75% male) were included: 186 (46.5%) patients had CKD stage 1 or 2; 93 (23.3%) had CKD stage 3a; 82 (20.5%) had CKD stage 3b; and 39 (9.8%) had CKD stage 4 or 5 prior to LVAD implantation. During a median follow-up of 179 days (IQR 28–627), 32,629 creatinine measurements were available. Improvement of kidney function was noticed in every preoperative CKD-stage group. Following this improvement, estimated glomerular filtration rates regressed to baseline values for all CKD stages. Patients showing early renal function improvement were younger and in worse preoperative condition. Moreover, survival rates were higher in patients showing early improvement (69% vs 56%, log-rank P = 0. 013). Conclusions: Renal function following LVAD implantation is characterized by improvement, steady state and subsequent deterioration. Patients who showed early renal function improvement were in worse preoperative condition, however, and had higher survival rates at 2 years of follow-up.

Aims: Many heart transplant recipients will develop end-stage renal disease in the post-operative course. The aim of this study was to identify the long-term incidence of end-stage renal disease, determine its risk factors, and investigate what subsequent therapy was associated with the best survival. Methods and results: A retrospective, single-centre study was performed in all adult heart transplant patients from 1984 to 2016. Risk factors for end-stage renal disease were analysed by means of multivariable regression analysis and survival by means of Kaplan–Meier. Of 685 heart transplant recipients, 71 were excluded: 64 were under 18 years of age and seven were re-transplantations. During a median follow-up of 8.6 years, 121 (19.7%) patients developed end-stage renal disease: 22 received conservative therapy, 80 were treated with dialysis (46 haemodialysis and 34 peritoneal dialysis), and 19 received a kidney transplant. Development of end-stage renal disease (examined as a time-dependent variable) inferred a hazard ratio of 6.45 (95% confidence interval 4.87–8.54, P < 0.001) for mortality. Tacrolimus-based therapy decreased, and acute kidney injury requiring renal replacement therapy increased the risk for end-stage renal disease development (hazard ratio 0.40, 95% confidence interval 0.26–0.62, P < 0.001, and hazard ratio 4.18, 95% confidence interval 2.30–7.59, P < 0.001, respectively). Kidney transplantation was associated with the best median survival compared with dialysis or conservative therapy: 6.4 vs. 2.2 vs. 0.3 years (P < 0.0001), respectively, after end-stage renal disease development. Conclusions: End-stage renal disease is a frequent complication after heart transplant and is associated with poor survival. Kidney transplantation resulted in the longest survival of patients with end-stage renal disease.

Aims A significant proportion of left ventricle assist device (LVAD) patients have very difficult transthoracic echocardiographic images. The aim of this study was to find an echocardiographic window which would provide better visualization of the heart in LVAD patients with limited acoustic windows. Methods and results Based on the anatomic relationships in LVAD patients, a right intercostal transhepatic approach was proposed. By using a computer simulator, we searched for the appropriate probe orientation. Further, 15 ambulatory LVAD patients (age 56 ± 15 years, 73% males) underwent two echocardiographic studies: one normal transthoracic echocardiography following the institutional protocol (Echo 1) and a second study which included the transhepatic approach (Echo 2). The two exams were performed by two different sonographers and the results validated by a third observer for agreement. The transhepatic intercostal window was feasible in all patients, with an image quality allowing good visualization of structures in 93%. Precise quantification of the left ventricular (LV) and right ventricular (RV) function was achieved more often in the Echo 2 (10 vs. 3 patients for LV, P = 0.03 and 14 vs. 8 patients for RV, P = 0.04). A significant difference existed also in the quantification of the LVAD inflow cannula flow by pulsed Doppler (11 patients in Echo 2 vs. 3 patients in Echo 1, P = 0.009). Conclusion This is the first study describing a new echocardiographic window in LVAD patients. The transhepatic window may provide better quantification of left and RV dimensions and function and improvement in Doppler interrogation of the inflow cannula.

Background Activation of the inflammatory response in heart failure (HF) may initially serve as a compensatory mechanism. However, on the longer term, this physiological phenomenon can become disadvantageous. Temporal patterns of inflammatory proteins other than CRP have not yet been investigated in patients with stable HF. Purpose We aimed to evaluate the association of 17 serially measured cytokines and cytokine receptors with clinical outcome in patients with stable heart failure. Methods In 263 patients, 1984 serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (IQR: 1.4–2.5) years. The primary endpoint (PE) composed of cardiovascular mortality, HF-hospitalization, heart transplantation, and LVAD. We selected baseline blood samples in all patients, as well as the two samples closest to the primary endpoint, and the last sample available in event-free patients. Thus, in 567 samples we measured 17 cytokines and cytokine receptors using the Olink Proteomics Cardiovascular III multiplex assay. Associations between biomarkers and PE were investigated by joint modelling. Results Median age was 68 (IQR: 59–76) years, with 72% men, 74% NYHA class I-II and a median ejection fraction of 30% (23–38%). 70 patients reached a PE. After adjustment for clinical characteristics (age, sex, diabetes, atrial fibrillation, NYHA class at baseline, diuretics and systolic blood pressure), 7 biomarkers were associated with the PE (Figure). Interleukin-1 receptor type 1 (IL1RT1) showed the strongest association: HR 2.65 [95% CI: 1.78–4.21]) per standard deviation change in level (NPX) at any point in time during follow-up, followed by Tumor necrosis factor receptor 1 (TNF-R1): 2.25 [1.66–3.08], and C-X-C motif chemokine 16 (CXCL16): 2.18 [1.59–3.04]. After adjustment for baseline N-terminal pro–B-type natriuretic peptide, high-sensitive troponin T and C-reactive protein however, only IL1RT1 and TNF-R1 remained significantly associated with the PE. Conclusion Repeatedly measured levels of several cytokines and cytokine receptors are independently associated with clinical outcome in stable HF patients. These results suggest that repeated measurements of these biomarkers, in addition to established cardiac biomarkers, may contribute to personalized risk assessment and herewith better identify high-risk patients. Figure 1. Associations between levels of cytokines and cytokine receptors and the primary endpoint. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the Jaap Schouten Foundation and the Noordwest Academie.

Supplemental Digital Content is available in the text., Background. Previous studies on the association between cytomegalovirus (CMV) infection and cardiac allograft vasculopathy (CAV) were conducted on patients transplanted in the prevalganciclovir prophylaxis era. The aim of our study is to evaluate this relation in heart transplantation (HTx) recipients treated according to current prophylactic and immunosuppressive regimens. Methods. This single-center retrospective study included all consecutive adult patients that underwent HTx between January 1, 2000, and May 31, 2018. Clinically relevant CMV infection was defined as either plasma CMV DNAemia ≥ 1000 IU/mL with/without clinical symptoms or

Purpose Poor left ventricular (LV) function may affect the physiological intraventricular blood flow and physiological vortex formation. The aim of this study was to investigate the pattern of intraventricular blood flow dynamics in patients with LV assist devices (LVADs) using echocardiographic particle image velocimetry. Materials and methods This prospective study included 17 patients (mean age 57 ± 11 years, 82% male) who had received an LVAD (HeartMate 3, Abbott Laboratories, Chicago, Illinois, USA) because of end-stage heart failure and poor LV function. Eleven (64%) patients had ischemic cardiomyopathy, and six patients (36%) had nonischemic cardiomyopathy. All patients underwent echocardiography, including intravenous administration of an ultrasound-enhancing agent (SonoVue, Bracco, Milan, Italy). Echocardiographic particle image velocimetry was used to quantify LV blood flow dynamics, including vortex formation (Hyperflow software, Tomtec imaging systems Gmbh, Unterschleissheim, Germany). Results Contrast-enhanced ultrasound was well tolerated in all patients and was performed without adverse reactions or side effects. The LVAD function parameters did not change during or after the ultrasound examination. The LVAD flow was on average 4.3 ± 0.3 L/min, and the speed was 5247 ± 109 rotations/min. The quantification of LV intraventricular flow demonstrated substantial impairment of vortex parameters. The energy dissipation, vorticity, and kinetic energy fluctuation indices were severely impaired. Conclusions Echo particle velocimetry is safe and feasible for the quantitative assessment of intraventricular flow in patients with an LVAD. The intraventricular LV flow and vortex parameters are severely impaired in these patients.

Background: Left ventricular assist devices (LVADs) improve quality of life and long-term survival in advanced heart failure, but device related infections (DRI) remain cumbersome. We evaluated the diagnostic capability of FDG-PET/CT and the additive value of semi-quantitative analysis for the diagnosis of DRI. Methods: LVAD recipients undergoing FDG-PET/CT between December 2012 and August 2020 for suspected DRI were retrospectively included. FDG-PET/CT was performed and evaluated according to EANM guidelines and assessors were blinded to the clinical context of included patients. Final clinical diagnosis of driveline infection and/or central device infection, based on multidisciplinary consensus and findings during surgery whenever performed, was used as the reference for the diagnosis. Results: 44 patients were evaluated for 62 episodes of suspected DRI. Clinical evaluation established driveline infection in 33 (54%) episodes, central device infection in 8 (14%) and combined infection in 2 (4%). Visual analysis of FDG-PET/CT achieved a sensitivity and specificity of 0.83 and 0.73, respectively, for driveline infections, while semi-quantitative analysis found comparable results (p=0.77). For central device component infections, visual analysis of FDG-PET/CT achieved a sensitivity and specificity of 1.0 and 0.26, respectively, while semi-quantitative analysis using SUVratio (background liver) achieved a sensitivity and specificity of 1.0 and 0.8, respectively. Both SUVmax and SUVratio outperformed visual analysis (pConclusions: FDG-PET/CT is a valuable tool for the assessment of DRI in LVAD recipients. Semiquantitative analysis significantly increases specificity of FDG-PET/CT for the analysis of central device components and should be considered in equivocal cases after visual analysis.

This report describes the first heart transplantation recipient with acute biventricular heart failure symptoms caused by a post-myocarditis state, late after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No other viral pathogens could be detected. Computed tomography angiography did not show cardiac allograft vasculopathy, and myocardial biopsy demonstrated no clinically relevant rejection. Subsequent cardiovascular magnetic resonance imaging revealed extensive epicardial delayed enhancement without myocardial edema. Heart failure medication was initiated and an implantable cardioverter defibrillator was implanted (due to non-sustained ventricular tachycardias), leading to a partial recovery of the ejection fraction. Further studies are needed to investigate the number of heart transplant recipients with myocardial damage after a SARS-CoV-2 infection.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Partnership UMCG Siemens for building the future of Health (PUSH) Background Left ventricular assist devices (LVADs) are increasingly used for the treatment of end-stage heart failure. LVADs improve quality of life and long-term survival, but device specific infections remain cumbersome. These infections can lead to life threatening complications and are difficult to diagnose with conventional radiological imaging. In this study, FDG-PET/CT accuracy for the diagnosis of LVAD specific infections was evaluated with specific focus on potential confounders and the additive value of semi-quantitative analysis. Materials/methods All LVAD recipients with an available FDG-PET/CT from September 2013 until August 2020 in two LVAD centres in the Netherlands, with a suspicion of driveline and/or central device infection were included. FDG-PET/CT was performed according to European Association of Nuclear Medicine (EANM) guidelines. Potential confounders were documented and assessors were blinded to the clinical context of included patients. Assessment of FDG-PET/CT was performed visually and semi-quantitatively with 6 regions of interest alongside the driveline and central device components. The final clinical diagnosis of either driveline infection or central device infection, based on findings during surgical intervention or multidisciplinary consensus, was used as the reference for diagnosis. Results In total 38 patients (average age 55 years, 84% males) were evaluated for a total of 55 episodes of suspected device-specific infection. Clinical evaluation established driveline infection in 28 cases, central device infection in 7 and combined infection in 4. Visual analysis obtained a sensitivity and specificity of 0.83 and 0.75 respectively, in differentiation between infected and non-infected drivelines. Visual analysis of FDG-PET/CT of central device components showed excellent sensitivity: 1.0, but suffered from poor specificity: 0.23. Semi-quantitative analysis using a SUVmax was comparable to visual analysis for establishing driveline infections, with a sensitivity and specificity of 0.80 and 0.84 respectively, while for central device infections, semi-quantitative analysis using a SUVratio outperformed visual analysis, with a sensitivity and specificity reaching 0.88 and 0.90 respectively. Conclusions FDG-PET/CT is a valuable tool for the assessment of device-specific infections in LVAD recipients. Semi-quantitative analysis can significantly increase diagnostic accuracy of FDG-PET/CT for the analysis of the central device components and should be considered in cases where the diagnosis cannot be rejected based on visual analysis.

We describe the first patient with a left ventricular assist device (LVAD) driveline infection caused by Mycobacterium chelonae presenting with persistent infection despite conventional antibiotics. Treatment was successful with surgical debridement, driveline exit relocation, and a 4-month period of antibiotics. In the case of a culture-negative LVAD driveline infection, non-tuberculous mycobacteria should be considered. This case illustrates that multidisciplinary collaboration is essential in providing optimal care for LVAD patients.

Pulmonary hypertension (PH) type II (classified by the World Health Organization) is a common complication in chronic left‐sided heart failure. In advanced heart failure therapy, fixed PH is an absolute contraindication for heart transplantation after which a left ventricular assist device (LVAD) is the only remaining option. With remote monitoring, we can now continuously evaluate the pulmonary artery pressures during long‐term LV unloading by the LVAD. In this case, we demonstrate that fixed PH can be reversed with LVAD implantation, whereby previous thoughts of this concept should be redefined in the era of assist devices.

OBJECTIVESThe purpose of this study was to describe pre- and postoperative data from the EUROMACS registry with regard to indications, for and survival and complication rates of patients with primary continuous flow and pulsatile biventricular long-term assist devices (BiVADs) versus total artificial hearts (TAHs) or left ventricular assist devices (LVADs) + short-term right ventricular assist device (RVAD) implants.METHODSWe investigated patients who received implants between 1 January 2011 and 21 October 2017. Clinical baseline information about comorbidities, laboratory results, medical and device therapies and echocardiographic, haemodynamic and right ventricle (RV) parameters were evaluated along with the rates of deaths and complications.RESULTSA total of 413 of 3282 patients (12.5%) needed a biventricular pump. We investigated 37 long-term BiVADs, 342 LVAD + short-term RVAD implants and 34 TAHs. Minor differences were found in the baseline characteristics of our population, which had an overall high morbidity profile. The 1-year survival rate was 55% for patients with a continuous flow BiVAD; 52% for patients with an LVAD + short-term RVAD; 37% for patients with pulsatile BiVADs; and 36% for patients with a TAH. No statistical difference was observed among the groups. Over 50% of patients with BiVAD support were classified as INTERMACS profiles 1 and 2. The percent of patients with ambulatory heart failure (INTERMACS 4‒7) undergoing BiVAD implants was modest at CONCLUSIONSThe mortality rate after BiVAD support was high. Survival rates and adverse events were statistically not different among the investigated groups. In the future, composite study end points examining quality of life and adverse events beyond survival may help in shared decision-making prior to general mechanical circulatory support, particularly in patients with BiVAD implants.

AimsWe aim to study the feasibility and clinical value of pulmonary artery pressure monitoring with the CardioMEMS™device in order to optimize and guide treatment in patients with a HeartMate3left ventricular assist device (LVAD).Methods and resultsIn this single-centre, prospective pilot study, we will include10consecutive patients with New YorkHeart Association Class IIIb or IV with Interagency Registry for Mechanically Assisted Circulatory Support Classes2–5scheduledfor implantation of a HeartMate3LVAD. Prior to LVAD implantation, patients will receive a CardioMEMS sensor, for dailypulmonary pressure readings. The haemodynamic information provided by the CardioMEMS will be used to improvehaemodynamic status prior to LVAD surgery and optimize the timing of LVAD implantation. Post-LVAD implantation, thehaemodynamic changes will be assessed for additive value in detecting potential complications in an earlier stage (bleedingand tamponade). During the outpatient clinic phase, we will assess whether the haemodynamic feedback can optimize pumpsettings, detect potential complications, and further tailor the clinical management of these patients.ConclusionsThe HEMO-VAD study is thefirst prospective pilot study to explore the safety and feasibility of usingCardioMEMS for optimization of LVAD therapy with additional (remote) haemodynamic information.

Objective This article investigates whether longitudinally measured fibrinolysis factors are associated with cardiac events in patients with chronic heart failure (CHF). Methods A median of 9 (interquartile range [IQR] 5–10) serial, tri-monthly blood samples per patient were prospectively collected in 263 CHF patients during a median follow-up of 2.2 (IQR 1.4–2.5) years. Seventy patients (cases) reached the composite endpoint of cardiac death, heart failure hospitalization, left ventricular assist device, or heart transplantation. From all longitudinal samples, we selected baseline samples in all patients and the last two samples before the event in cases or the last sample available in event-free patients. Herein, we measured plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and soluble urokinase plasminogen activator surface receptor (suPAR). Associations between temporal biomarker patterns during follow-up and the cardiac event were investigated using a joint model. Results Cases were on average older and showed higher New York Heart Association class than those who remained event-free. They also had lower blood pressures, and were more likely to have diabetes, renal failure, and atrial fibrillation. Longitudinally measured PAI-1, uPA, and suPAR were independently associated with adverse cardiac events after correction for clinical characteristics (hazard ratio [95% confidence interval]) per standard deviation increase of 2.09 (1.28–3.45) for PAI-1, 1.91 (1.18–3.24) for uPA, and 3.96 (2.48–6.63) for suPAR. Serial measurements of tPA were not significantly associated with the event after correction for multiple testing. Conclusion Longitudinally measured PAI-1, uPA, and suPAR are strongly associated with adverse cardiac events during the course of CHF. If future research confirms our results, these fibrinolytic factors may carry potential for improved, and personalized, heart failure surveillance and treatment monitoring.

Background: The Heart Failure (HF) Meta-score may be useful in predicting prognosis in patients with primary prevention cardiac resynchronization defibrillators (CRT-D) considering the competing risk of appropriate defibrillator shock versus mortality. Methods: Data from 648 consecutive patients from two centers were used for the evaluation of the performance of the HF Meta-score. The primary endpoint was mortality and the secondary endpoint was time to first appropriate implantable cardioverter-defibrillator (ICD) shock or death without prior appropriate ICD shock. Fine-Gray model was used for competing risk regression analysis. Results: In the entire cohort, 237 patients died over a median follow-up of 5.2 years. Five-year cumulative incidence of mortality ranged from 12% to 53%, for quintiles 1 through 5 of the HF Meta-score, respectively (log-rank P < 0.001). Compared with the lowest quintile, mortality risk was higher in the highest quintile (HR 6.9; 95%CI 3.7–12.8). The HF Meta-score had excellent calibration, accuracy, and good discrimination in predicting mortality (C-statistic 0.76 at 1-year and 0.71 at 5-year). The risk of death without appropriate ICD shock was higher in risk quintile 5 compared to quintile 1 (sub HR 5.8; 95%CI 3.1–11.0, P < 0.001). Conclusions: Our study demonstrated a good ability of the HF Meta-score to predict survival in HF patients treated with CRT-D as primary prevention. The HF Meta-score proved to be useful in identifying a subgroup with a significantly poor prognosis despite a CRT-D.

Background Left ventricular assist devices (LVADs) are increasingly used in the treatment of end-stage heart failure. One important limitation in the follow-up of these patients is the very difficult echocardiographic image, because of the interposition of implanted materials. Case summary We present here a case series of LVAD patients with severely limited transthoracic echocardiographic windows in whom the echocardiographic analysis of the left and right ventricular function could be obtained from a very unusual approach, using a right intercostal transhepatic window, allowing visualization of the heart chambers and quantification of function even in these very challenging cases. In one case, the result was confirmed by computed tomography. In the second case, computed tomography images were unreliable because of strong artefacts from the LVAD system and implantable cardioverter-defibrillator leads, but the transhepatic approach still provided sufficient image quality in order to allow the imaging follow-up of the patient. In the third case, the transhepatic window was the only approach that provided echocardiographic images, and due to the good visualization of the heart cavities, this imaging technique was considered sufficient for follow-up studies in this stable subject with LVAD as destination therapy. Discussion The transhepatic window may represent a good alternative in selected LVAD patients with very difficult acoustic access in traditional transthoracic views. Modified or alternate echocardiographic windows may reduce the need for invasive procedures (transoesophageal echocardiography) or imaging methods using radiations.

Purpose We aimed to investigate the determinants and clinical impact of dynamic moderate-to-severe (mod-sev) aortic regurgitation (AR) on the long-term outcomes following LVAD implantation. Methods The international multicenter registry data from the International Society of Heart and Lung Transplantation Mechanically Assisted Circulation Support (IMACS) registry was used. All adult LVAD patients, implanted between January 2013 until September 2017, with at least 1 echocardiogram available following implantation were included. Longitudinal evolution of AR was modeled using logistic mixed effect models. Joint modelling was used to link the dynamic longitudinal evolution of AR to a relative risk model for morality (Cox). Outcomes are presented by hazard ratios and two simulated Kaplan Meier curves presenting two identical patients. Results In total, 12.810 patients (median age 58 [48-66], 78.5% male) were included, with 36.343 echocardiograms available. Following LVAD implantation, mod-sev AR was observed in 1.660 (12.9%) patients on 2.660 different echocardiograms. The strongest predictors for the development of mod-sev AR included mild AR at baseline and prolonged LVAD support. Moreover, concomitant aortic valve replacement, opposed to repair surgery, was associated with a substantial lower risk for the development of mod-sev AR. Both the presence of mod-sev AR, as the pace of the probability of AR was changing (slope), were significantly associated with increased mortality. Survival following the development significant AR is heavily impacted, as displayed in Figure 1. Conclusion The development of significant AR occurs approximately in 1 in 8 patients following LVAD implantation. Subsequent mortality seems largely dictated by the pace of the development of mod-sev AR, with a faster development of AR being associated with less favorable outcomes.

Aim: To investigate the temporal evolution of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor (LDLR) and myeloperoxidase (MPO) in relation to clinical outcome in chronic heart failure (CHF). Methodology & results: Trimonthly blood sampling was performed during a median follow-up of 2.2 (IQR 1.4–2.5) years in 263 CHF patients. Seventy patients reached the primary end point (PE) (cardiovascular death, heart transplantation, left ventricular assist device implantation or HF-hospitalization). MPO level was independently associated with the PE; the adjusted (for clinical factors) hazard ratio (aHR) per standard deviation difference in MPO was 1.71 (95% CI: 1.23–2.43) at any time during follow-up. PCSK9 level (HR: 1.45 [1.04–2.06]) and LDLR (HR: 0.66 [0.49–0.87]) were statistical significantly associated with the PE but only in unadjusted analyses. Slope of temporal MPO evolution (aHR: 1.34 [1.12–1.76] per 0.1 standard deviation/year difference in slope) and LDLR (aHR: 0.78 [0.61–0.90]) however, were associated with PE. Conclusion: Temporal patterns of MPO and LDLR are independently associated with clinical outcome in CHF, which illustrates the importance of assessing temporal evolutions. Clinical trial registration information: registered in ClinicalTrials.gov, number NCT01851538 . https://clinicaltrials.gov/ct2/show/NCT01851538 .

Aims: Recent reports demonstrated that patients with heart failure (HF) might have an increased risk to develop malignancies. This is also seen in patients with chronic kidney disease (CKD). Immunosuppression in heart transplantation (HT) recipients additionally increases the risk of malignancies. The aim of this study was to determine the relation between HF duration and CKD pre-HT and the risk of malignancy development post-HT. Methods and results: We included all adult HT recipients transplanted between January 2000 and November 2017 in our centre. Patients were excluded if they died or were retransplanted within 3 months post-HT. Clinical characteristics were retrospectively collected. Sixty out of 250 patients (24%) developed a malignancy after a median of 66 months [interquartile range 33–108] post-HT. In multivariable Cox regression analysis, HF duration was not a risk factor for all malignancies or solid organ malignancies post-HT [hazard ratio (HR) 1.033 (0.974–1.096), P = 0.281 and HR 1.036 (0.958–1.120), P = 0.376, respectively]. Age [HR 1.051 (1.016–1.086), P = 0.004] and CKD pre-HT [HR 2.173 (1.236–3.822), P = 0.007] were independent risk factors for all malignancies. CKD pre-HT [HR 2.542 (1.142–5.661), P = 0.022] increased the risk for solid organ malignancies. Exclusion of patients with durable mechanical circulatory support in the analysis did not alter the significance of these risk factors. Conclusions: Duration of HF pre-HT was not associated with malignancy risk post-HT. CKD was an independent risk factor for malignancies post-HT. More studies are needed to investigate this association.

Post-cardiotomy extracorporeal life support (PC-ECLS) has seen a substantial increase in use over the past 10 years. PC-ECLS can be a life-saving procedure and is mostly applied in the presence of unexpected, severe cardio-respiratory complication. Despite PC-ECLS being critical in allowing for organ recovery, it is unfortunately closely connected with an unpredictable outcomes, high morbidity, and, even in the case of cardiac function improvement, potential sustained disabilities that have a life-changing impact for the patient and his or her family. Since the decision to start PC-ECLS is made in an acute setting, there is often only limited or no time for self-determined choices. Due to the major impact of the intervention, it would be highly desirable to obtain informed consent before starting PC-ECLS, since the autonomy of the patient and shared-decision making are two of the most important ethical values in modern medicine. Recent developments regarding awareness of the impacts of a prolonged intensive care stay make this a particularly relevant topic. Therefore, it would be desirable to develop a structural strategy that takes into account the likelihood of such an intervention and the wishes and preferences of the patient, and thus the related autonomy of the patient. This article proposes key points for such a strategy in the form of a PC-ECLS informed consent, a do-(not-)mechanical-circulatory-support order (D(N)MCS), and specific guidelines to determine the extent of the shared decision making. The concept presented in this article could be a starting point for improved and ethical PC-ECLS treatment and application.

Background/Introduction Despite improved surgical techniques and pump designs, LVAD therapy remains associated with high mortality and morbidity. CardioMEMS guided hemodynamic optimization shortly pre-LVAD surgery could improve the long-term post-surgery outcomes. Purpose The aim of this analysis was to investigate the feasibility of pre-operative optimization using the hemodynamic monitoring provided by the CardioMEMS in patients with an LVAD surgery, to improve the long-term outcome compared to a cohort of historical controls. Methods Ten consecutive chronic heart failure patients, with an INTERMACS Class 2–5, scheduled for (semi-) elective HeartMate 3 (HM3) LVAD surgery were enrolled in the HEMO-VAD pilot study. All patients received a CardioMEMS device prior to LVAD surgery. The daily hemodynamic readings were used to guide the patient optimization process pre- and post-operatively. Aims of hemodynamic optimization were the normalization of the mean pulmonary artery pressure (mPAP), decongesting of the right ventricle (RV) and optimization of the renal function. Patients were categorized into optimized patients (mPAP ≤25mmHg) and non-optimized mPAP (mPAP >25mmHg). Additionally, a historical cohort, consisting of 24 (semi-) elective HM3 LVAD recipients were included in this analysis. The outcome of this analysis was the event-free survival of the combined endpoint of all-cause mortality, RV failure, acute kidney injury (AKI) and/or renal replacement therapy (RRT) during the first 12 months post-LVAD surgery (time to first event analysis). Results The median age was 60.3 [51.6–66.3], 58.7 [53.4–61.9] and 60.1 [53.5–65.2] years in the optimized patients, non-optimized patients and historical controls, respectively (p=0.90). Of the optimized patients, 66.7% were men, compared to 75.0% and 100.0% of the non-optimized patients and historical controls, respectively (p=0.02). During the first year post-LVAD surgery, the combined endpoint occurred in 19 patients, five (83%) events occurred in the non-optimized patients, and 14 (58%) events in the historical controls, while no (0%) events occurred in the optimized patients (p=0.018) (Figure). Conclusion(s) This analysis demonstrated the feasibility of hemodynamic guided optimization pre-LVAD surgery using the CardioMEMS. The hemodynamic optimized patients were at very low risk for all-cause mortality, right-sided HF, and AKI/RRT compared to non-optimized patients or historical controls. Figure 1. Event-free survival for the combined endpoint (all-cause mortality, right ventricular failure, and acute kidney injury and/or renal replacement therapy). Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): This work was supported by Abbott with an independent research grant, partially covering personnel costs. This study was investigator-initiated and was designed, conducted, interpreted and reported independently of the funder

Purpose The aim of the study was to analyze early mortality after continuous-flow left ventricular assist device (LVAD) implantation which remains high. Methods We analyzed consecutive (n = 2689) patients from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) undergoing continuous-flow LVAD implantation. The primary outcome was early (

Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy.

Data on the risk of aortic root thrombosis in patients with aortic valve replacement (AVR) and left ventricular assist device (LVAD) surgery are scarce. Two out of nine patients receiving AVR concomitant with LVAD surgery and two out of two patients receiving AVR on LVAD support, at our centre, developed an aortic root thrombus, all diagnosed with computed tomography (CT) angiography. These results demonstrate that patients with concomitant AVR and LVAD surgery, or AVR on LVAD support, have an increased risk of aortic root thrombosis. Therefore, early anti‐thrombotic therapy and vigilant diagnostic follow‐up, using CT scans, are warranted to prevent thromboembolic events.

Background: Orthotopic heart transplantation (OHT) is the gold standard treatment in end-stage heart disease. Controversy remains whether bicaval OHT is superior to biatrial OHT in both early and late outcomes. This study aimed to provide an overview of the early and late outcomes in patients who underwent a bicaval or biatrial OHT. Methods: A systematic literature search was performed for articles published before December 2017. Studies comparing adult patients undergoing biatrial OHT and bicaval OHT were included. Early outcomes were pooled in odds ratios and late outcomes were pooled in rate ratios. Late survival was visualized by a pooled Kaplan-Meier curve. Results: A total of 36 publications were included in the meta-analysis, counting 3555 patients undergoing biatrial OHT and 3208 patients undergoing bicaval OHT. Early outcomes in mortality, tricuspid regurgitation, mitral regurgitation, and permanent pacemaker implantation differed significantly in favor of the bicaval OHT patients. Long-term survival was significantly better in patients undergoing bicaval vs biatrial OHT (hazard ratio, 1.32; 95% confidence interval, 1.1-1.6; P = .008). Also, late tricuspid regurgitation was less frequently seen in the bicaval OHT patients (rate ratio, 2.14; 95% CI, 1.17-3.94; P = .014). Conclusions. This systematic review with meta-analysis shows that bicaval OHT results in more favorable early and late outcomes for patients undergoing a bicaval OHT compared with a biatrial OHT. Therefore, bicaval OHT should be considered as preferable technique for OHT.

Purpose In patients supported by a ventricular assist device (VAD) major infections are a frequently reported adverse event with increased morbidity and mortality. The purpose of this study was to investigate the possible association of infections and cerebrovascular accidents (CVAs). Methods An analysis of the European Registry for Patients Assisted with Mechanical Circulatory Support (EUROMACS) was performed identifying all patients aged ≥18 years with a LVAD or BiVAD implantation. Infections were categorized as VAD-specific infections, VAD-related infections and non-VAD infections. An extended Kaplan-Meier analysis for the risk of CVA and mortality with infection as a time-dependent covariate was performed. Furthermore, a multivariable cox proportional hazard model was performed including 24 variables. Results For this analysis 3784 patients were included, with 45 patients being supported by a BiVAD and 3739 by an LVAD. The majority of patients were male (83.2%) and 60.5% had an INTERMACS patient profile 2 or 3. During follow-up, 3108 major infections were identified in 1385 (36.6%) of the patients, while 673 CVAs were identified in 545 (14.4%) of the patients. Extended Kaplan-Meier analysis with first infection as time-dependent covariate revealed a hazard ratio for CVA of 1.95 (95% CI: 1.57-2.36; p Conclusion Both VAD-related and VAD-specific infections are associated with significant increased risk of CVA, but non-VAD infections are not.

Introduction Right ventricular failure (RVF) is recognized as a major cause of morbidity and mortality after left ventricular assist device (LVAD) implantation and identifying patients at risk remains a challenge. Given its structural complexity, it is not possible to fully assess the RV from one echocardiographic 2D plane and entire free wall visualization is more challenging in advanced heart failure patients with very severely dilated left ventricles. Our centre previously introduced a novel multi-plane approach whereby four different RV free wall segments (lateral, anterior, inferior and inferior coronal – figure 1) can be imaged from the same echocardiographic position using focused RV views and electronic plane rotation. Purpose The aim of the study was to determine the feasibility of using multi-plane echocardiography (MPE) to quantify right ventricular free wall longitudinal strain (RV-FWLS) in a small cohort of advanced heart failure patients prior to LVAD implantation. Methods Sixteen advanced heart failure patients underwent detailed RV assessment by MPE prior to LVAD implantation (median - 15 [6.3-29.8] days before). Feasibility and values of RV-FWLS were retrospectively assessed by an experienced sonographer on each of the 4 free wall segments using specialised RV strain analysis software. Feasibility was confirmed if all regions of the free wall were visualised and tracked appropriately throughout the cardiac cycle. Standard right heart 2D echo parameters and pre-implant right heart catheterisation (RHC) data were also collated. Results Mean RV-FWLS and feasibility in the four segments were as follows: lateral -12.4 ± 4.3% (81.3%); anterior -12.7 ± 6.1% (62.5%); inferior -11.8 ± 4.7% (75.0%); inferior coronal -11.6 ± 3.9% (43.8%). TAPSE values on the same segments were feasible in 100% of cases and mean values were as follows: lateral 15.1 ± 4.9mm; anterior 15.3 ± 4.7mm; inferior 13.4 ± 5.2mm; inferior coronal 11.4 ± 5.1mm. Mean pulmonary artery pressure (mPAP) measured by RHC was 27.2 ± 11mmHg. There was a slightly stronger negative correlation of RV-FWLS with increased mPAP in the lateral, anterior and inferior RV free wall segments compared to TAPSE (r²: -0.07-0.11 v -0.01-0.05). Conclusion There is reasonable feasibility for assessing RV-FWLS using MPE in 3 out of the 4 free wall segments and mean values were considerably lower than normal reference values. A stronger negative correlation with increasing mPAP suggests that RV dysfunction may be detected better by strain than by TAPSE measurement in pre-LVAD recipients. Larger, multi-centre studies are required to further assess these preliminary findings. Abstract P931 Figure. Multi-plane RV imaging with strain

Aims Sufficient myocardial recovery with the subsequent explantation of a left ventricular assist device (LVAD) occurs in approximately 1-2% of the cases. However, follow-up data about this condition are scarcely available in the literature. This study aimed to report the long-term outcomes and clinical management following LVAD explantation. Methods and results An analysis of the European Registry for Patients with Mechanical Circulatory Support was performed to identify all adult patients with myocardial recovery and successful explantation. Pre-implant characteristics were retrieved and compared with the non-recovery patients. the follow-up data after explantation were collected via a questionnaire. A Kaplan-Meier analysis for freedom of the composite endpoint of death, heart transplantation, LVAD reimplantion, or heart failure (HF) relapse was conducted. A total of 45 (1.4%) cases with myocardial recovery resulting in successful LVAD explantation were identified. Compared with those who did not experience myocardial recovery, the explanted patients were younger (44 vs. 56 years, P < 0.001), had a shorter duration of cardiac disease (P < 0.001), and were less likely to have ischaemic cardiomyopathy (9% vs. 41.8%, P < 0.001). Follow-up after explantation could be acquired in 28 (62%) cases. the median age at LVAD implantation was 43 years (inter-quartile range: 29-52), and 23 (82%) were male. Baseline left ventricular ejection fraction was 18% (inter-quartile range: 10-20%), and 60.7% of the patients had Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 or 2. Aetiologies of HF were dilated cardiomyopathy in 36%, myocarditis in 32%, and ischaemic in 14% of the patients, and 18% had miscellaneous aetiologies. the devices implanted were HeartMate II in 14 (50%), HVAD in 11 (39%), HeartMate 3 in 2 (7%), and 1 unknown with a median duration of support of 410 days (range: 59-1286). the median follow-up after explantation was 26 months (range 0.3-73 months), and 82% of the patients were in New York Heart Association Class I or II. Beta-blockers were prescribed to 85%, angiotensin-converting enzyme inhibitors to 71%, and loop diuretics to 50% of the patients, respectively. Freedom from the composite endpoint was 100% after 30 days and 88% after 2 years. Conclusions the survival after LVAD explantation is excellent without the need for heart transplantation or LVAD reimplantation. Only a minority of the patients suffer from a relapse of significant HF., European Association for Cardio-Thoracic Surgery, The European Association for Cardio-Thoracic Surgery supported this work.

BACKGROUND: Patients with end stage heart failure are increasingly being bridged to heart transplant (BTT) with mechanical circulatory support (MCS), however the association between a left ventricular assist device (LVAD) BTT strategy and post-transplant renal outcomes is unclear. The aim of this study was to analyze the association of LVAD BTT with the development of post-transplant renal failure using a large national registry. METHODS: We queried the 2009-2018 United Network for Organ Sharing (UNOS) registry for all adults undergoing first-time heart or heart-kidney transplantation and stratified patients by use of pre-transplant durable LVAD. The primary outcome of interest was post-transplant renal failure, which was evaluated with multivariable logistic regression. RESULTS: 18,307 patients met inclusion criteria including 7,887 (43%) and 10,420 (57%) that were and were not bridged to transplant with an LVAD, respectively. BTT patients had slightly better baseline renal function (eGFR 68.7 vs 65.8 mL/min, p

Cardiovascular inflammation and vascular endothelial dysfunction are involved in chronic heart failure (CHF), and cellular adhesion molecules are considered to play a key role in these mechanisms. We evaluated temporal patterns of 12 blood biomarkers of cell adhesion in patients with CHF. In 263 ambulant patients, serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (1.4&ndash, 2.5) years. The primary endpoint (PE) was a composite of cardiovascular mortality, HF hospitalization, heart transplantation and implantation of a left ventricular assist device and was reached in 70 patients. We selected the baseline blood samples in all patients, the two samples closest to a PE, or, for event-free patients, the last sample available. In these 567 samples, associations between biomarkers and PE were investigated by joint modelling. The median age was 68 (59&ndash, 76) years, with 72% men and 74% New York Heart Association class I&ndash, II. Repeatedly measured levels of Complement component C1q receptor (C1qR), Cadherin 5 (CDH5), Chitinase-3-like protein 1 (CHI3L1), Ephrin type-B receptor 4 (EPHB4), Intercellular adhesion molecule-2 (ICAM-2) and Junctional adhesion molecule A (JAM-A) were independently associated with the PE. Their rates of change also predicted clinical outcome. Level of CHI3L1 was numerically the strongest predictor with a hazard ratio (HR) (95% confidence interval) of 2.27 (1.66&ndash, 3.16) per SD difference in level, followed by JAM-A (2.10, 1.42&ndash, 3.23) and C1qR (1.90, 1.36&ndash, 2.72), adjusted for clinical characteristics. In conclusion, temporal patterns of C1qR, CDH5, CHI3L1, EPHB4, ICAM2 and JAM-A are strongly and independently associated with clinical outcome in CHF patients.

Purpose Acute kidney injury (AKI) frequently occurs after heart transplantation (HTx), but its relation to preoperative right heart hemodynamic (RHH) parameters remains unknown. Therefore, we aimed to determine their predictive properties for postoperative AKI severity within 30 days after HTx. Methods From 1984 to 2016, all consecutive HTx recipients (n = 595) in our tertiary referral center were included and analyzed for the occurrence of postoperative AKI staged by the kidney disease improving global outcome criteria. The effects of preoperative RHH parameters on postoperative AKI were calculated using logistic regression, and predictive accuracy was assessed using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and area under the receiver operating characteristic curves (AUC). Results Postoperative AKI occurred in 430 (72%) patients including 278 (47%) stage 1, 66 (11%) stage 2, and 86 (14%) stage 3 cases. Renal replacement therapy (RRT) was administered in 41 (7%) patients. Patients with higher AKI stages had also higher baseline right atrial pressure (RAP; median 7, 7, 8, and in RRT 11 mmHg, p trend = 0.021), RAP-to-pulmonary capillary wedge pressure ratio (median 0.37, 0.36, 0.40, 0.47, p trend = 0.009), and lower pulmonary artery pulsatility index (PAPi) values (median 2.83, 3.17, 2.54, 2.31, p trend = 0.012). Higher RAP and lower PAPi values independently predicted AKI severity [adjusted odds ratio (OR) per doubling of RAP 1.16 (1.02–1.32), p = 0.029; of PAPi 0.85 (0.75–0.96), p = 0.008]. Based on IDI, NRI, and delta AUC, inclusion of these parameters improved the models’ predictive accuracy. Conclusions Preoperative PAPi and RAP strongly predict the development of AKI early after HTx and can be used as early AKI predictors. Electronic supplementary material The online version of this article (10.1007/s00134-018-5159-z) contains supplementary material, which is available to authorized users.

Renal dysfunction is an important component of chronic heart failure (CHF), but its single assessment does not sufficiently reflect clinically silent progression of CHF prior to adverse clinical outcome. Therefore, we aimed to investigate temporal evolutions of glomerular and tubular markers in 263 stable patients with CHF, and to determine if their patient-specific evolutions during this clinically silent period can dynamically predict clinical outcome. We determined the risk of clinical outcome (composite endpoint of Heart Failure hospitalization, cardiac death, Left Ventricular Assist Device placement, and heart transplantation) in relation to marker levels, slopes and areas under their trajectories. In each patient, the trajectories were estimated using repeatedly measured glomerular markers: creatinine/estimated glomerular filtration rate (eGFR), cystatin C (CysC), and tubular markers: urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1, plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL). During 2.2 years of follow-up, we collected on average 8 urine and 9 plasma samples per patient. All glomerular markers predicted the endpoint (univariable hazard ratio [95% confidence interval] per 20% increase: creatinine: 1.18 [1.07-1.31], CysC: 2.41[ 1.81-3.41], and per 20% eGFR decrease: 1.13[1.05-1.23]). Tubular markers, NAG, and KIM-1 also predicted the endpoint (NAG: 1.06[1.01-1.11] and KIM-1: 1.08[1.04-1.11]). Larger slopes were the strongest predictors (creatinine: 1.57[1.39-1.84], CysC: 1.76 [1.52-2.09], eGFR: 1.59[1.37-1.90], NAG: 1.26[1.11-1.44], and KIM-1: 1.64[1.38-2.05]). Associations persisted after multivariable adjustment for clinical characteristics. Thus, during clinically silent progression of CHF, glomerular and tubular functions deteriorate, but not simultaneously. Hence, patient-specific evolutions of these renal markers dynamically predict clinical outcome in patients with CHF.

Aims Patients with a left ventricular assist device (LVAD) are challenging to evaluate using conventional imaging techniques, such as standard echocardiography (SE). The aim of this pilot study was to evaluate the potential of contrast echocardiography (CE) for the evaluation of the left ventricle (LV). Methods and results This prospective study included 14 ambulatory patients (mean age 58 ± 9 years, 79% male) with a LVAD (all HeartMate 3, Abbott Laboratories, Chicago, IL, USA). Nine (64%) patients had an ischaemic cardiomyopathy, and 5 (36%) had a non-ischaemic cardiomyopathy. All patients underwent SE and CE using intravenous administration of Sonovue contrast agent (Bracco, Milan, Italy). The echocardiograms were assessed by three observers, using a standard 17-segment model of the LV. Left ventricular end-diastolic volume (LVEDV) was assessed using the biplane Simpson method. The contrast agent was well tolerated by all patients, without any side effects. Overall, SE allowed visualization of 57% of LV segments (135/238) and CE allowed visualization of 79% of LV segments (187/238), P < 0.001. Per patient, SE resulted in visualization of 9.6 ± 5.2 segments and CE was able to visualize 13.4 ± 5.8 segments (P < 0.001). Administration of contrast agent significantly improved the assessment of LVEDV (feasibility SE: 36% vs. CE: 79%, P < 0.05). Conclusion Routine use of a contrast agent appears safe when used in patients having a new third generation LVAD and may enhance the diagnostic accuracy of transthoracic echocardiography in these patients. LV size determination can be obtained more often due to improved LV visualization using contrast agent.

Background We examined the prognostic information of detailed temporal patterns of N-terminal proBNP (NT-proBNP), high-sensitive troponin T (HsTNT), and C-reactive protein (CRP) in patients with chronic heart failure. Methods The first inclusion round (2011-2013, N = 263) from the ongoing Bio-SHiFT study was used. Biomarkers were measured at baseline and every 3 months. The primary end point (PE) comprised heart failure hospitalization, cardiovascular mortality, cardiac transplantation, and left ventricular assist device implantation. Associations between temporal biomarker patterns and the PE were investigated by joint modeling. Results Mean age was 67 ± 12 years, 72% were men, 95% had systolic dysfunction, and 73% were in New York Heart Association class I or II. Median follow-up was 2.2 (interquartile range 1.4-2.5) years. We used 2,022 blood samples (median 9 [interquartile range 5-10] per patient), and 70 (27%) patients reached the PE. Temporal patterns of NT-proBNP, HsTNT, and CRP level were associated with the PE (multivariable-adjusted hazard ratio per doubling of biomarker: NT-proBNP 2.28 (95% CI 1.82-2.86), HsTNT 2.05 (1.63-2.58), and CRP 1.65 (1.30-2.08). A combined 3-biomarker model demonstrated independent associations for the temporal patterns of NT-proBNP and CRP level (hazard ratios 2.06 [1.53-2.79] and 1.38 [1.01-1.89], respectively). Instantaneous change in biomarker level was also independently associated with the PE for NT-proBNP and CRP. Long-term biomarker elevation showed an association for NT-proBNP. Conclusions Temporal patterns representing evolution of level and rate of change in level of NT-proBNP and CRP, and long-term elevation of NT-proBNP were independently associated with adverse prognosis in patients with chronic heart failure. Individual patterns of change and combining multiple biomarkers could carry value for prognostication and for therapy guidance.

OBJECTIVES Bleeding is a common complication following left ventricular assist device (LVAD) implantation. The goal of this study was to investigate the incidence, predictors and clinical outcome of early bleeding events in patients after LVAD implantation. METHODS A total of 83 patients (age 50 ± 13 years, 76% men) had an LVAD implanted [77% HeartMate II, 19% HeartMate 3 (Abbott, Chicago, IL, USA)] over a period of 11 years. Patients were included consecutively. An early bleeding event was defined as the need for thoracic surgical re-exploration or transfusion with >4 units of packed red blood cells before discharge. RESULTS Overall, 39 (47%) patients (age 50 ± 14 years, 77% men) experienced an early bleeding event [median time 6 days (interquartile range 1-9 days)]. Furthermore, 10 (26%) of these patients had ≥2 bleeding events. Twelve of the 14 (92%) patients with venoarterial extracorporeal membrane oxygenation (ECMO) support before LVAD implantation experienced an early bleeding event versus 27 of the 69 (39%) patients without ECMO support (P

We determined the temporal effects of neurohormonal antagonists and loop diuretics on serially assessed (3-monthly) cardiorenal biomarkers, functional status, and clinical outcomes in 250 patients with chronic heart failure (CHF) with reduced ejection fraction. In blood, we measured NT-proBNP, troponin T, C-reactive protein, creatinine, cystatin C; in urine, N-acetyl-beta-d-glucosaminidase and kidney-injury-molecule-1. Angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) were inversely associated with cardiac impairment, inflammation, and renal tubular damage, but not with glomerular dysfunction. Diuretics were associated with worse biomarker profiles and with a hazard ratio for adverse clinical outcome of 1.12 (95% confidence interval: 1.03-1.22) per 40 mg higher doses. ACE-inhibitors/ARBs were more frequently downtitrated and diuretics more frequently uptitrated in patients who experienced endpoints than in those who did not. In conclusion, a decrease or withholding of ACE-inhibitors/ARBs solely based on glomerular function is not justified because of the beneficial effects on the heart, inflammation, and renal tubules. Higher and increased diuretic doses mark progression towards endstage CHF.