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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.

Introduction The aim of the present study was to assess the safety and efficacy of renal sympathetic denervation (RDN) in patients with heart failure with reduced ejection fraction (HFrEF). Methods We randomly assigned 50 patients with a left ventricular ejection fraction (LVEF) ≤ 35% and NYHA class ≥ II, in a 1:1 ratio, to either RDN and optimal medical therapy (OMT) or OMT alone. The primary safety endpoint was the occurrence of a combined endpoint of cardiovascular death, rehospitalisation for heart failure, and acute kidney injury at 6 months. The primary efficacy endpoint was the change in iodine-123 meta-iodobenzylguanidine (123I‑MIBG) heart-to-mediastinum ratio (HMR) at 6 months. Results Mean age was 60 ± 9 years, 86% was male and mean LVEF was 33 ± 8%. At 6 months, the primary safety endpoint occurred in 8.3% vs 8.0% in the RDN and OMT groups, respectively (p = 0.97). At 6 months, the mean change in late HMR was −0.02 (95% CI: −0.08 to 0.12) in the RDN group, versus −0.02 (95% CI: −0.09 to 0.12) in the OMT group (p = 0.95) whereas the mean change in washout rate was 2.34 (95% CI: −6.35 to 1.67) in the RDN group versus −2.59 (95% CI: −1.61 to 6.79) in the OMT group (p-value 0.09). Conclusion RDN with the Vessix system in patients with HFrEF was safe, but did not result in significant changes in cardiac sympathetic nerve activity at 6 months as measured using 123I‑MIBG.

While the efficacy of the intracardiac defibrillators (ICDs) for primary prevention is not disputed, the relevant studies were carried out a long time ago. Most pertinent trials, including MADIT‐II, SCD‐Heft, and DEFINITE, recruited patients more than 20 years ago. Since then, improved therapeutic modalities including, in addition to cardiac resynchronization therapy, mineralocorticoid receptor antagonists, angiotensin receptor‐neprilysin inhibitors, and, most recently, inhibitors of sodium‐glucose cotransporter 2, have lowered present‐day rates of mortality and of sudden cardiac death. Thus, nowadays, ICD therapy may be less effective than previously reported, and not as beneficial as many people currently believe. However, criteria for ICD implantation remain very inclusive. The patient must (only) be symptomatic and have ejection fraction (EF) ≤ 35%. The choice of EF 35% is notable because the average EF in all large trials was much lower, and clinical benefit was mainly limited to EF ≤ 30%. This EF cut‐off value defines a substantial portion of potential ICD recipients. It seems therefore reasonable to limit ICD eligibility criteria in the EF range 30–35% to patients at highest risk only. We discuss and present some rational criteria to assist the clinician in improving risk stratification for preventive ICD implantation.

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.

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

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 It is uncertain that chronic heart failure (CHF) patients are susceptible to renal tubular damage with that of worsening renal function (WRF) preceding clinical outcomes.Hypothesis Changes in tubular damage biomarkers are stronger predictors of subsequent clinical events than changes in creatinine (Cr), and both have different clinical determinants.Methods During 2.2 years, we repeatedly simultaneously collected a median of 9 blood and 8 urine samples per patient in 263 CHF patients. We determined the slopes (rates of change) of the biomarker trajectories for plasma (Cr) and urinary tubular damage biomarkers N-acetyl-beta-d-glucosaminidase (NAG), and kidney-injury-molecule (KIM)-1. The degree of tubular injury was ranked according to NAG and KIM-1 slopes: increase in neither, increase in either, or increase in both; WRF was defined as increasing Cr slope. The composite endpoint comprised HF-hospitalization, cardiac death, left ventricular assist device placement, and heart transplantation.Results Higher baseline NT-proBNP and lower eGFR predicted more severe tubular damage (adjusted odds ratio, adj. OR [95%CI, 95% confidence interval] per doubling NT-proBNP: 1.26 [1.07-1.49]; per 10 mL/min/1.73 m(2) eGFR decrease 1.16 [1.03-1.31]). Higher loop diuretic doses, lower aldosterone antagonist doses, and higher eGFR predicted WRF (furosemide per 40 mg increase: 1.32 [1.08-1.62]; spironolactone per 25 mg decrease: 1.76 [1.07-2.89]; per 10 mL/min/1.73 m(2) eGFR increase: 1.40 [1.20-1.63]). WRF and higher rank of tubular injury individually entailed higher risk of the composite endpoint (adjusted hazard ratios, adj. HR [95%CI]: WRF 1.9 [1.1-3.4], tubular 8.4 [2.6-27.9]; when combined risk was highest 15.0 [2.0-111.0]).Conclusion Slopes of tubular damage and WRF biomarkers had different clinical determinants. Both predicted clinical outcome, but this association was stronger for tubular injury. Prognostic effects of both appeared independent and additive.

Aims: Evidence on the association of macrophage- and neutrophil-related blood biomarkers with clinical outcome in heart failure patients is limited, and, with the exception of C-reactive protein, no data exist on their temporal evolution. We aimed to investigate whether temporal patterns of these biomarkers are related to clinical outcome in patients with stable chronic heart failure (CHF). Methods and Results: In 263 patients with CHF, we performed serial plasma measurements of scavenger receptor cysteine-rich type 1 protein M130 (CD163), tartrate-resistant acid phosphatase type 5 (TRAP), granulins (GRN), spondin-1 (SPON1), peptidoglycan recognition protein 1 (PGLYRP1), and tissue factor pathway inhibitor (TFPI). The Cardiovascular Panel III (Olink Proteomics AB, Uppsala, Sweden) was used. During 2.2 years of follow-up, we collected 1984 samples before the occurrence of the composite primary endpoint (PE) or censoring. For efficiency, we selected 567 samples for the measurements (all baseline samples, the last two samples preceding the PE, and the last sample before censoring in event-free patients). The relationship between repeatedly measured biomarker levels and the PE was evaluated by joint models. Mean (±standard deviation) age was 67 ± 13 years; 189 (72%) were men; left ventricular ejection fraction (%) was 32 ± 11. During follow-up, 70 (27%) patients experienced the PE. Serially measured biomarkers predicted the PE in a multivariable model adjusted for baseline clinical characteristics [hazard ratio (95% confidence interval) per 1-standard deviation change in biomarker]: CD163 [2.07(1.47–2.98), P < 0.001], TRAP [0.62 (0.43–0.90), P = 0.009], GRN [2.46 (1.64–3.84), P < 0.001], SPON1 [3.94 (2.50–6.50), P < 0.001], and PGLYRP1 [1.62 (1.14–2.31), P = 0.006]. Conclusions: Changes in plasma levels of CD163, TRAP, GRN, SPON1, and PGLYRP1 precede adverse cardiovascular events in patients with CHF.

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.

Objectives Invasively measured fractional flow reserve (FFR) is associated with outcome in heart transplant (HTx) patients. Coronary computed tomography angiography (CCTA)–derived FFR (FFRct) provides additional functional information from anatomical CT images. We describe the first use of FFRct in HTx patients. Methods HTx patients underwent CCTA with FFRct to screen for cardiac allograft vasculopathy. FFRct was measured distal to each coronary stenosis > 30% and FFRct ≤ 0.8 indicated hemodynamically significant stenosis. FFRct was also measured at the most distal location of each vessel. Overall distal FFRct was calculated as the mean of the distal values in the left, right, and circumflex coronary artery in each patient. Results Seventy-three patients (age 56 (42–65) years, 63% males) at 11 (8–16) years after HTx were included. Eighteen (25%) patients had a focal hemodynamically significant stenosis (stenosis > 30% with FFRct ≤ 0.8). In the 55 patients without a hemodynamically significant focal FFRct stenosis (FFRct > 0.80), the distal left anterior descending artery FFRct was p = 0.93). Conclusions FFRct performed on CCTA scans of HTx patients demonstrated that 25% of patients had a focal coronary stenosis with FFRct ≤ 0.8. Even without a focal stenosis, FFRct values are often abnormal in HTx patients. Key Points • This is the first report describing the use of FFRct in in heart transplant patients. • FFRct identifies patients after heart transplantation with hemodynamically significant coronary stenosis. • Even without a focal stenosis, FFRct values are often abnormal in heart transplant patients.

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.

Purpose of ReviewWe aim to summarize recent insights and provide an up-to-date overview on the role of intra-aortic balloon pump (IABP) counterpulsation in cardiogenic shock (CS).Recent FindingsIn the largest randomized controlled trial (RCT) of patients with CS after acute myocardial infarction (AMICS), IABP did not lower mortality. However, recent data suggest a role for IABP in patients who have persistent ischemia after revascularization. Moreover, in the growing population of CS not caused by acute coronary syndrome (ACS), multiple retrospective studies and one small RCT report on significant hemodynamic improvement following (early) initiation of IABP support, which allowed bridging of most patients to recovery or definitive therapies like heart transplant or a left ventricular assist device (LVAD).SummaryRoutine use of IABP in patients with AMICS is not recommended, but many patients with CS either from ischemic or non-ischemic cause may benefit from IABP at least for hemodynamic improvement in the short term. There is a need for a larger RCT regarding the role of IABP in selected patients with ACS, as well as in patients with non-ACS CS.

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

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.

Background: We aimed to assess differences in clinical characteristics, prognosis, and the temporal evolution of circulating biomarkers in male and female patients with HFrEF. Methods: We included 250 patients (66 women) with chronic heart failure (CHF) between 2011 and 2013 and performed trimonthly blood sampling during a median follow-up of 2.2 years [median (IQR) of 8 (5–10) urine and 9 (5–10) plasma samples per patient]. After completion of follow-up we measured 8 biomarkers. The primary endpoint (PE) was the composite of cardiac death, cardiac transplantation, left ventricular assist device implantation, and hospitalization due to acute or worsened CHF. Joint models were used to determine whether there were differences in the temporal patterns of the biomarkers between men and women as the PE approached. Results: A total of 66 patients reached the PE of which 52 (78.8%) were male and 14 (21.2%) were female. The temporal patterns of all studied biomarkers were associated with the PE, and overall showed disadvantageous changes as the PE approached. For NT-proBNP, HsTnT, and CRP, women showed higher levels over the entire follow-up duration and concomitant numerically higher hazard ratios [NT-proBNP: women: HR(95%CI) 7.57 (3.17–21.93), men: HR(95%CI) 3.14 (2.09–4.79), p for interaction = 0.104, HsTnT: women: HR(95%CI) 6.38 (2.18–22.46), men: HR(95%CI) 4.91 (2.58–9.39), p for interaction = 0.704, CRP: women: HR(95%CI) 7.48 (3.43–19.53), men: HR(95%CI) 3.29 [2.27–5.44], p for interaction = 0.106). In contrast, temporal patterns of glomerular and tubular renal markers showed similar associations with the PE in men and women. Conclusion: Although interaction terms are not statistically significant, the associations of temporal patterns of NT-proBNP, HsTnT, and CRP appear more outspoken in women than in men with HFrEF, whereas associations seem similar for temporal patterns of creatinine, eGFR, Cystatin C, KIM-1 and NAG. Larger studies are needed to confirm these potential sex differences.

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.

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

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.

Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is useful in the evaluation of cardiac allograft vasculopathy (CAV) in heart transplant (HTx) recipients. The current study evaluated the long-term prognostic value of stress SPECT MPI for predicting all-cause mortality and cardiac events in HTx recipients. The study population consisted of 166 HTx recipients (mean age 54 ± 10 years, 84% male) who underwent exercise or dobutamine stress 99mTc-tetrofosmin SPECT MPI for the assessment of CAV. An abnormal SPECT MPI was defined as the presence of a fixed or a reversible perfusion defect. Endpoints were all-cause mortality, cardiac mortality, and non-fatal myocardial infarction (MI). MPI abnormalities were detected in 55 patients (33%), including fixed defects in 28 patients (17%), partially reversible in 17 patients (10%), and completely reversible defects in 10 patients (6%). During a median follow-up of 12.8 years (range 0-15, mean follow-up 9.5 years), 109 (66%) patients died (all-cause mortality), of which 67 (40%) were due to cardiac causes. A total of 5 (3%) patients experienced a non-fatal MI. HTx recipients with a normal stress 99mTc-tetrofosmin SPECT MPI had a significantly better prognosis as compared with those with an abnormal study, up to 5 years after the initial test. The presence of a reversible perfusion defect was a significant predictor of all-cause mortality, cardiac mortality, and major cardiac events, during the entire follow-up period. Stress 99mTc-tetrofosmin SPECT MPI provides valuable prognostic information for the prediction of long-term outcome in HTx recipients. Patients with a normal stress 99mTc-tetrofosmin SPECT MPI have a significantly better prognosis as compared with those with an abnormal study, up to 5 years after initial testing.

PURPOSE: Invasively measured fractional flow reserve (FFR) is associated with outcome in heart transplant (HTx) patients. Non-invasive coronary computed tomography angiography (CCTA)-derived FFR (FFRct) provides additional functional information from anatomical CT images. The anatomical model of the coronary arteries derived from CCTA is used to calculate the FFRct values at each point in the coronary arteries. We describe the first use of FFRct in a cohort of HTx patients. METHODS: HTx patients underwent CCTA with FFRct as part routine follow-up to screen for cardiac allograft vasculopathy (CAV). FFRct was performed off-site by a company. FFRct was measured distal to each coronary stenosis >30% and at the most distal location of each of the 3 major coronary arteries (right, left anterior descending and circumflex coronary artery). Overal distal FFRct was calculated as the mean of 3 vessels per patient. During 90-day follow-up, performance of additional tests for coronary assessment and revascularization were recorded. RESULTS: 73 patients (age 56 (42-65) years, 63% males) at 11 (8-16) years after HTx were included. In the 54 patients without a hemodynamically significant focal FFRct stenosis (FFRct >0.80), the distal left anterior descending artery FFRct was

PURPOSE: Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease that affects heart transplant patients (HTx). Routine screening for CAV is warranted. We evaluated the feasibility and utility of cardiac CT to screen for CAV in 100 consecutive HTx patients at our center. METHODS: From Feb 2018 to Jan 2019 all consecutive HTxs who were more than five-years post-transplant were converted from using stress myocardial perfusion imaging to cardiac CT for the annual assessment of CAV. CAV was scored (0 (absent), 1 (mild), 2 (moderate), 3 (severe)) based on coronary CT angiography (CCTA) findings and compared with the most recently known CAV score before CCTA. RESULTS: CCTA was performed in 99 out of 100 patients who were planned for cardiac CT (56 (42-63) years, 65% men, and 11 (8-16) years post-transplant), 1 patient underwent only a calcium scan due to IV access problems. The median Agatston calcium score was 6 (0-85), and 38 patients had no detectable calcium. CCTA showed new obstructive coronary disease (>50% stenosis) in 20 patients. The CAV score was reclassified based on CCTA findings in 37 patients (p

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.

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.

Purpose Continuous-flow left ventricular assist device (LVAD) therapy has become an indispensable treatment modality for patient with end-stage heart failure. Therefore, our aim is to evaluate our results with 2 contemporary generations of the mainstream LVAD device types, being the HeartMate II (HMII) and HeartMate 3 (HM3), with over one and a half decade of experience, in the treatment of end-stage heart failure patients within our tertiary referral center. Methods We included all adult patients implanted with an LVAD from December 2006 until December 2019. The primary outcome was early and late survival. Secondary outcomes included multiple adverse events, both early and late. Results In total, 133 patients (mean age 56 ± 12 year, 77% male) underwent implantation of an LVAD: 64 (48%) received an HMII and 69 (52%) received an HM3, with a median follow-up period of 768 days [IQR 221-1206] and 427 days [IQR 269 - 962], respectively. The HM3 patients were compared to the HM II group older (57 ±10 vs 49±12), had a higher median body mass index (25.6 [IQR 22.5-28.1] vs 22.8 [IQR 20.7-25.1]) and less frequently implanted as bridge-to-transplant (26 (30%) vs 61 (70%)). However, despite the increased age and rate of morbidity, survival (both early and late) were similar for both patient groups, as displayed in the Figure. Furthermore, bleeding events, rates of stroke, re-thoracotomy rates, and confirmed pump-thrombosis rates did not differ between both groups. Conclusion Despite the older age and relatively higher risk profile of the second era HM 3 patients compared with the HM II patients, the rate of adverse events did not differ between both groups. Similarly, the survival remains favorable regardless of a lower transplantation rate and higher destination therapy strategy in the HM3 group. Therefore, LVAD therapy remains an excellent modality to improve both the quality of life and survival in a broad range of end-stage heart failure patients.

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.

Chronisch hartfalen is een ernstige ziekte met een slechte prognose, waarvan de incidentie in Nederland (door o.a. vergrijzing) de komende decennia zal blijven toenemen. Steeds vaker wordt daarvoor een linkerventrikelsteunhart (LVAD) geplaatst. Maar terminale zorg voor een patient met een LVAD vergt een andere benadering dan terminale palliatieve zorg bij eindstadium hartfalen zonder LVAD. Aan de hand van een casus uit onze praktijk willen wij dit in deze klinische les beschrijven.

We report implantation of a left ventricular assist device (LVAD) in a patient with Parkinson's disease. Postoperative fluid overload together with insufficient LVAD output in the setting of vasodilation through levodopa likely caused renal hypoperfusion and acute kidney injury. A patient like ours, therefore, requires the highest possible increase of HM3 RPM and LVAD flow early after surgery.

Purpose The difference in renal function between bridge-to-transplantation (BTT) and medically managed patients undergoing heart transplantation (HTx) is unknown. This study aimed to depict the difference in renal function between BTT and medically managed patients pre- and post-HTx. Methods A retrospective single-center cohort study was conducted including all HTx patients that were transplanted since the introduction of left ventricular assist device (LVAD) therapy in our center in 2006. Patients were dichotomized according to BTT and medical management strategy. Results In total, 164 patients were included, of whom 135 were medically managed (mean age 49.3±10.4), and 29 BTT patients (mean age 48.5±11.8). Median time on LVAD support pre-HTx was 551 days, interquartile range [230-863]. At 12 months prior to HTx, the BTT patients had higher mean eGFR compared to the medically managed patients (87 ml/min/1.73m2 vs 63 ml/min/1.73m2, p Outcomes, including mortality and primary graft dysfunction, following HTx were not significantly different Conclusion In conclusion, patients who are bridged with LVAD therapy had a higher mean renal function at the time of HTx. Additionally, patients who received BTT therapy preserved longer an improved renal function at 1-year pre- and post-HTx.

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.

Coronary artery fistulae (CAF) represent an abnormal communication bypassing the myocardial capillary bed between a coronary artery and either a cardiac chamber (coronary-cameral CAF) or a vascular structure from systemic or pulmonary circulation (coronary-vascular CAF). CAF represent a congenital anomaly in 0.2% of the population, but are more frequently found in heart transplant recipients (8%), mostly as coronary-right ventricle (RV) CAF caused by endomyocardial biopsy used for monitoring of rejection1,2. Other complications of myocardial biopsy include perforation of the RV wall and tricuspid valve damage2. Several case reports have shown successful transcatheter closure of CAF3,4. We aimed to analyse ...

Background Many patients eligible for left ventricular assist device (LVAD) therapy already have an implantable cardioverter defibrillator (ICD) and/or pacemaker (PM). However, electromagnetic interference (EMI) between the LVAD and ICD/PM devices could be cumbersome. Purpose The aim of this study was to investigate the prevalence of EMI between different types of ICD/PM in patients implanted with an LVAD. Methods Data was obtained through a retrospective electronic patient database analysis of all LVAD patients (including HeartMate II (HMII) and HeartMate 3 (HM3)), from our tertiary referral center, from December 2006 to February 2019. Device switches have also been taken into account due to elective replacement. Electromagnetic interference was defined as ICD/PM telemetry interference (i.e. the inability to interrogate ICD/PM) Results In total, 109 patients received an LVAD (mean age 52±12, 83% male), Of these, 86 (79%) patients had an ICD/PM at LVAD implantation. One patient with ICD/PM was excluded from further analysis because of missing follow-up data. Among the 85 patients (45 HM II and 40 HM3), 11 (13%) experienced EMI; 5 (11%) with a HM II and 6 (15%) with a HM3 (p=0.59). The implanted ICD/PM devices were from Medtronic (n=25), Abbott (n=23), Biotronik (n=18), Boston Scientific (n=18), and Microport (n=1). EMI with the HM II was present in St Jude/Abbott devices (type 1 Atlas, 1 Unify, 1 Fortify, and 2 Promote). In HM 3 LVAD patients, EMI was observed in Biotronik devices (1 Lumax, 1 Ilivia, 1 Ilesto, and 2 Iperia) and Medtronic (Claria). Conclusion In our cohort of HM II and HM 3 LVAD patients, at least one in seven patients experienced EMI from either the HM II or HM3 LVAD with the ICD/PM. Electromagnetic interference from HM II LVADs was mainly present in patients with St Jude/Abbott ICD/PM devices However, in the HM3 patients, EMI was mainly present in patients with Biotronik devices, which is not yet widely known!

Background Cardiac allograft vasculopathy (CAV) remains a leading cause of morbidity and mortality after heart transplantation. Annual screening is recommended to improve risk stratification and early treatment of CAV and is often performed with invasive coronary angiography (ICA). Coronary computed tomography angiography (CCTA) with CCTA-derived fractional flow reserve (FFRct) might be a non-invasive alternative to ICA for the surveillance of CAV providing both anatomical and functional information. Purpose To describe our initial results with CCTA and FFRct for detection of CAV in a cohort of heart transplant patients. Methods Heart transplant patients who underwent CCTA with FFRct as part of routine annual assessment for CAV were enrolled in a prospective registry from February 2018 to February 2019 in a single center. The most recently known CAV score (0–3) based on invasive angio and single photon emission computed tomography (SPECT) before CCTA was recorded. CCTA image quality was scored as non-diagnostic, moderate, good or excellent. FFRct analysis was performed off-site by a commercial company. For each coronary stenosis >30%, an FFRCTvalue distal to the stenosis was measured. For the RCA, LAD and CX without a stenosis, the FFRct value in the most distal location in the vessel was recorded. CAV classification was rescored based on CCTA. Demographics, additional diagnostic tests, and treatment plans were evaluated including major adverse events (MACE) during 90-day follow-up. Results 65 patients (56 (39–65) years (median/ 25th–75thpercentile), 40% women) that were 11 (7–16) years after transplantation were included. The most recent CAV score was 0 in 52 patients (80%) and 1 or 2 in 13 patients. CCTA image quality was good or excellent in 59 (91%) patients. CCTA reclassified CAV scores in 32 (49%) patients to 33 patients with CAV 0, 18 patients with CAV 1, 9 patients with CAV 2 and 5 patients with CAV 3. In 17 patients (26%) at least one stenosis with FFRct ≤0.80 was detected including 11 patients with single vessel disease, 5 with two-vessel disease and one with three-vessel disease. In the 48 patients without a focal stenosis, mean distal FFRct values were 0.88 (0.86–0.91), 0.87 (0.85–0.90) and 0.90 (0.86–0.91) at less than 10, 10–15 or more than 15 years after transplantation, respectively (p=0.457). Additional tests were performed in 10 (15%) patients (1 SPECT and 10 invasive coronary angiographies), which resulted in revascularization by PCI in 6 (9%) patients. No MACE occurred during 90-day follow-up. Conclusion CCTA with FFRct can be successfully performed in heart transplant patients, detects patients with significant coronary stenosis and CCTA leads to substantial reclassification of CAV grades. Acknowledgement/Funding FFRct analysis was performed as part of the ADVANCE registry which is supported by Heartflow Inc.

Background Lactate dehydrogenase (LDH) is considered as a biomarker of thrombotic events in patients receiving a left ventricular assist device (LVAD). Purpose This study aimed to investigate the evolution of LDH levels over time between patients supported with a HeartMate II (HMII), HeartMate 3 (HM3) or HeartWare (HVAD) LVAD during their first-year post implantation. Methods We analyzed in this multi-center retrospective study, all patients with HMII, HM3 and HVAD LVAD implanted between December 2006 and April 2017. Patients were classified into three groups based on their device type. Loess splines over time were used to depict the repeated measurements of LDH. Results In total, 134 patients received an LVAD (77% male, mean age 55 [46–61]), of whom 64 (48%) were HMII, 22 (16%) HM3 and 48 (36%) were HVAD. Loess splines over time indicate that there could be a considerable difference between evolution of LDH (Figure). During the first-year follow-up, 3 (5%) patients had a confirmed and 10 (16%) patients had a suspected pump thrombosis in the HMII group. For the HVAD, there were 6 (13%) patients with confirmed thrombosis and 1 (2%) case of suspected thrombosis, whereas none of the patients in the HM3 group experienced a suspected or confirmed pump thrombosis (p=0.01). The 1-year overall survival rate for HM II, HM3 and HVAD was 84%, 86% and 72% respectively (p=0.311). The overall stroke-free rate at one year was: 89%, 77% and 91% for HMII, HVAD and HM3 respectively (p=0.15). Means of observed LDH values over time Conclusion During the first-year post LVAD implantation, there appear to be different evolutions of LDH levels over time in HMII device patients compared to HVAD or HM3 device patients. Given differences in baseline hemolysis levels between devices, currently used LDH thresholds for detection of impending pump thrombosis may be less sensitive and thus thresholds may be device specific.

Background Predefined screening intervals and target levels do not account for variations in temporal patterns of biomarkers between individuals, which may hamper their potential use for therapy guidance. Conversely, a personalized screening approach with screening intervals and target levels based on the evolution of biomarkers in individual patients may further improve risk assessment and therapy guidance. Purpose We hypothesize that personalized screening intervals for N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements in patients with chronic heart failure (CHF) maximize information gain on the individual patient's disease progression, while minimizing the number of necessary measurements. We aim to compare such personalized scheduling of NT-proBNP measurements to a predefined fixed scheduling approach. Methods In 263 CHF patients from the Bio-SHiFT study, NT-proBNP was measured trimonthly according to a prespecified, fixed schedule [median: 9 (IQR: 5–10) measurements per patient].The primary composite endpoint (PE) comprised cardiac death, cardiac transplantation, left ventricular assist device implantation or heart failure hospitalization, and occurred in 70 patients (26.6%). Using joint models for time-to-event and longitudinal data, we modelled the association between repeated NT-proBNP measurements and the PE. Using the fitted joint model, for each patient at each follow-up visit, we determined the optimal time point of the next NT-proBNP measurement based on the patient's individual risk profile and the maximum information gain on the patient's prognosis as assessed by the Kullback-Leibler divergence. Personalized scheduling was compared to fixed (trimonthly) scheduling by means of a realistic simulation study, based on a replica of the study population included in the Bio-SHiFT study. In this simulation study, we stopped monitoring NT-proBNP to potentially enable appropriate timely intervention if the cumulative risk of PE exceeded an arbitrary risk threshold of 7.5% within 3-months. We compared personalized scheduling with fixed scheduling in terms of capability of identification of high-risk intervals (whether timely intervention was enabled before occurrence of PE), number of measurements needed, and costs. Results Compared to fixed scheduling, personalized scheduling saved on average 2 measurements [personalized; median: 7 (IQR: 7–8) vs. fixed; 9 (IQR: 8–10) measurements], while the start of the time-window identified for therapeutic intervention to avoid the occurrence of PE was similar in both approaches [personalized; median: 6.6 (IQR: 4.5–11.3) vs. fixed; 6.3 (IQR: 4.2–10.3) months before occurrence of PE]. Costs saved were €165 per patient per year. Figure 1 Conclusion Personalized scheduling of NT-proBNP measurements in CHF patients shows similar prognostic performance as fixed scheduling, but requires fewer NT-proBNP measurements. This may improve efficiency of natriuretic guided therapy, if the latter were to be installed. Acknowledgement/Funding Funding for this study was provided by the Jaap Schouten Foundation and Erasmus MC Efficiency Research grant

Purpose Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease that affects heart transplant (HT) patients. Routine surveillance for CAV is warranted. We evaluated the feasibility, utility and safety of cardiac CT to screen for CAV in HT patients. Methods From Feb 2018 to Jul 2019 all HT patients >four years post-HT were converted from using stress myocardial perfusion imaging for the annual CAV surveillance to cardiac CT (calcium score scan and CT angiography (CTA)). All first scans were included. Scans were scored for image quality (non-diagnostic, moderate, good, excellent), Agatston calcium score and coronary stenosis (0%, Results In total, 141 CT scans were included. CTA was performed in 140 out of 141 patients who were planned for cardiac CT (55 (43-64) years, 66% men, and 11 (8-16) years post-HT). One patient only had a calcium score due to no IV access. Mean heart rate during CTA was 75±11 beats per minute with beta-blockers given in 90 patients. Image quality was good/excellent in 124 (89%) scans. Median radiation dose was 2.1 (1.6-2.9) mSv. Median Agatston calcium score was 4 (0-73), 56 (40%) patients had no detectable calcium. CTA showed new obstructive coronary disease (≥50% stenosis) in 25 (18%) patients (Figure 1). CTA reclassified CAV score in 49 (35%) patients (p Conclusion Cardiac CT can be performed successfully in HT patients with good/excellent image quality and low radiation dose. CTA successfully detects significant CAV which leads to substantial reclassification of CAV grades.

Purpose Cardiac allograft vasculopathy (CAV) is a poorly understood, accelerated form of coronary artery disease in patients that underwent heart transplantation (HT), and substantially contributes to post-transplantation morbidity and mortality. Increasing evidence shows an active role for epicardial fat (EF) in the development of coronary artery disease, as a result of its inflammatory properties. Yet, whether the amount of EF is also related to CAV remains unknown. Hence, we investigated the association of epicardial fat volume (EFV) with CAV. Methods For this pilot study, we included post HT-patients whom underwent cardiac computed tomography (CCT) for CAV screening between February 2018 and January 2019. CCT included a non-enhanced CT (NECT) and CT angiography (CCTA). Using the NECT, we quantified the EFV using an automated algorithm (Fig 1.). CAV was graded on CCTA similar to the guidelines of the International Society for Heart and Lung Transplantation. The association of EFV with the presence and grade of CAV was investigated using binary- and ordinal logistical regression models, adjusted for recipient age and gender, time since HT and number of rejections pre-CCT. Results We included 74 patients, with a median age of 45 years [IQR 27-51] at HT of whom 29 were women. Median time since HT was 10.0 years [IQR 8.0-15.3]. CAV was prevalent in 28 (38%) patients, of whom 17 (61%) had CAV 1, 5 (18%) had CAV 2 and 6 (21%) had CAV 3. Median EFV was 198.5 [IQR 123.4-262.1] mm3. The median EFV was larger with higher CAV grades: 162.2 (CAV 0), 211.5 (CAV 1), 230.0 (CAV 2) and 278.3 (CAV 3) mm3 (p=0.031). Albeit not statistically significant, we found an association of EFV with the presence of CAV (odds ratio (OR) per 1-standard deviation increase in log-transformed EFV: 1.48 (95%CI: 0.80-2.72), p=0.21) and with CAV grade (OR 1.52 (95%CI: 0.85-2.71), p=0.15). Conclusion Our preliminary results show a promising trend towards an association of the amount of epicardial fat and the presence of CAV, which should be confirmed in larger studies.

Purpose Post-transplant diabetes mellitus (PTDM) is a frequent complication post-heart transplantation (HT). Moreover, PTDM has been associated with cardiovascular adverse events long-term post-HT. The golden standard to diagnose PTDM is an oral glucose tolerance test (OGTT). Studies investigating the incidence of PTDM long-term post-HT are missing. The aim was to investigate the prevalence of unknown PTDM long-term post-HT. Methods Data were prospectively collected from all adult HT patients who had an OGTT between August 2018 and October 2020. Patients with known DM, an active infection or active treatment of a malignancy were excluded as well as patients who did not want to undergo an OGTT. Either the patient came sober to the outpatient clinic for a regular appointment or visited the general practitioner when the distance to the hospital was too far. A fasting glucose was determined after which the patient was administered 75 grams of glucose in a 200 mL solution as advised by the American Diabetes Association. After two hours, glucose was measured again. Furthermore, glycated hemoglobin (HbA1c) was determined. Definitions of PTDM, pre-diabetes and no diabetes are mentioned in Table 1. Diabetes range tests were repeated after six weeks with another OGTT to confirm PTDM. Results Out of 251 patients, 148 patients were tested excluding 71 patients with known DM and 32 patients not able or willing to undergo an OGTT. Median age at OGTT was 54.5 [IQR 42.4-64.8] years and 60 (41%) were female. Main reason for HT was non-ischemic cardiomyopathy (n=118, 80%). Median time from HT until OGTT was 8.6 [IQR 4.8-14.4] years. Steroids were used in 90 (61%) patients and 134 (91%) patients used tacrolimus at the time of OGTT. In total, OGTT demonstrated new PTDM in 21 (14%) patients, pre-diabetes in 41 (28%) patients and no diabetes in 86 (58%) patients. Conclusion PTDM as well as pre-diabetes are frequently seen long-term post-HT. As such, systematic screening by OGTT is warranted for timely intervention as this may improve the long-term outcome.

Short-term mechanical circulatory support (MCS) is increasingly used as a bridge to decision in patients with refractory cardiogenic shock. Subsequently, these patients might be bridged to durable MCS either as a bridge to candidacy/transplantation, or as destination therapy. The aim of this study was to review support duration and clinical outcome of short-term MCS in cardiogenic shock, and to analyse application of this technology as a bridge to long-term cardiac support (left ventricular assist device, LVAD) from 2006 till June 2016. Using Cochrane Register of Trials, Embase and Medline, a systematic review was performed on patients with cardiogenic shock from acute myocardial infarction, end-stage cardiomyopathy, or acute myocarditis, receiving short-term MCS. Studies on periprocedural, post-cardiotomy and cardiopulmonary resuscitation support were excluded. Thirty-nine studies, mainly registries of heterogeneous patient populations (n = 4151 patients), were identified. Depending on the device used (intra-aortic balloon pump, TandemHeart, Impella 2.5, Impella 5.0, CentriMag and peripheral veno-arterial extracorporeal membrane oxygenation), mean support duration was (range) 1.6-25 days and the mean proportion of short-term MCS patients discharged was (range) 45-66%. The mean proportion of bridge to durable LVAD was (range) 3-30%. Bridge to durable LVAD was most frequently performed in patients with end-stage cardiomyopathy (22 [12-35]%). We conclude that temporary MCS can be used to bridge patients with cardiogenic shock towards durable LVAD. Clinicians are encouraged to share their results in a large multicentre registry in order to investigate optimal device selection and best duration of support.

Background: Several studies have suggested circulating microRNAs (miRs) are associated with heart failure, but these studies were small, and limited to single miR measurements.We examined 7 miRs which were previously linked to heart failure, and tested whether their temporal expression level predicts prognosis in a prospective cohort of chronic heart failure (CHF) patients.Methods and results: In 2011-2013, 263 CHF patients were included. At inclusion and subsequently every 3 months, we measured 7 miRs. The primary endpoint (PE) comprised heart failure hospitalization, cardiovascular mortality, cardiac transplantation and LVAD implantation. Associations between temporal miR patterns and the PE were investigated by joint modelling, which combines mixed models with Cox regression.Mean age was 67 +/- 13 years, 72% were men and 27% NYHA classes III-IV. We obtained 873 blood samples (median 3 [IQR 2-5] per patient). The PE was reached in 41 patients (16%) during a median follow-up of 0.9 [0.6-1.4] years. The temporal pattern of miR-22-3pwas independently associatedwith the PE (HR [95% CI] per doubling of level: 0.64 [0.47-0.77]). The instantaneous change in level (slope of the temporal miR pattern) of miR-22-3p was also independently associated with the PE (HR [95% CI] per doubling of slope: 0.33 [0.20-0.51]). These associations remained statistically significant after adjustment for temporal patterns of NT-proBNP, Troponin T and CRP.Conclusions: The temporal pattern of circulating miR-22-3p contains important prognostic and independent information in CHF patients. This concept warrants further investigation in larger series with extended follow-up. (C) 2017 The Authors. Published by Elsevier B.V.

Item does not contain fulltext BACKGROUND: We aimed to compare the prognostic value of a single "baseline" echocardiogram with repeated echocardiography in stable chronic heart failure (CHF) patients. We hypothesized that repeated echocardiograms would contain incremental prognostic information. METHODS: In the prospective Bio-SHiFT study, we performed 332 echocardiograms in 106 patients during a median follow-up of 2.3 years. The endpoint comprised HF hospitalization, left ventricular (LV) assist device implantation, heart transplantation, and cardiovascular death. We compared hazard ratios (HRs; adjusted for N-terminal pro-brain natriuretic peptide) from Cox models for the first available measurement with HRs from joint models, which model individual trajectories based on the repeated measurements and link these to the time-to-event data. RESULTS: The mean age of the patients was 58.1 years; 78.3% were male, 12.6% had New York Heart Association class >II, all had reduced ejection fraction, and the most common HF etiologies were cardiomyopathies (51%) and ischemia (40%). The endpoint occurred in 25 patients. Both the single measurements and the temporal trajectories were significantly associated with the endpoint (adjusted HR Cox model [95% CI] vs adjusted HR joint model [95% CI]): LV ejection fraction, 1.47 (0.93-2.31) vs 1.77 (1.13-2.93); diastolic LV diameter, 1.64 (1.09-2.47) vs 1.68 (1.12-2.57); systolic LV diameter, 1.72 (1.10-2.69) vs 1.68 (1.13-2.63); systolic left atrial diameter, 1.88 (1.18-3.00) vs 2.60 (1.48-4.97); E/A ratio, 2.73 (1.42-5.26) vs 3.87 (1.75-10.13); and E/e' ratio, 2.30 (1.38-3.84) vs 2.99 (1.68-6.19). None of the trajectories from the investigated parameters showed worsening prior to events. CONCLUSIONS: Although single baseline or repeatedly measured echocardiographic parameters were associated with the endpoint, all parameters remained on average stable during the 2.3 years of follow-up in this largely minimally symptomatic CHF cohort. Thus, regular echocardiographic monitoring of systolic or diastolic LV function within this time frame does not carry incremental prognostic information over a single baseline measurement.