Fully magnetically centrifugal left ventricular assist device and long-term outcomes: the ELEVATE registry.

BACKGROUND AND AIMS: HeartMate 3 (HM3) is a fully magnetically levitated continuous flow left ventricular assist device, which received CE marking in 2015. The ELEVATE Registry was initiated to collect real-world outcomes in patients treated with HM3 post-CE Mark approval. METHODS: A total of 540 subjects implanted at 26 centres between March 2015 and February 2017 were included in this registry. Of these, 463 received the device as a primary implant (primary implant cohort, PIC), 19 as a pump exchange (pump exchange cohort), and in 58 patients, only anonymized survival data were collected (anonymized cohort, AC). Patients in the PIC contributed to the baseline demographics, survival, adverse events, quality of life (QoL) (EuroQoL-5 Dimensions-5 Levels visual analogue scale), and functional capacity (6 min walk distance) assessments, while patients in the AC contributed only to survival. RESULTS: Primary implant cohort patients had a mean age of 56 years and were predominantly male (89%) with 48% ischaemic aetiology. The majority of subjects was designated bridge to transplant (66%) and had INTERMACS Profiles 1-3 (70%). At baseline, the subjects had poor functional capacity (104 ± 140 m) and impaired QoL (35 ± 19 points). The overall survival rate of the PIC was 63.3% and survival free of stroke was 58.1% at 5 years. Significant improvements in functional capacity and QoL were observed and maintained for 5 years (301 ± 131 m and 64 ± 20 points, respectively). CONCLUSIONS: Real-world data from the ELEVATE registry demonstrate an overall survival rate for primary implants of 63.3%. In the PIC, reductions in adverse events for patients in the extended follow-up and improved QoL and functional capacity were observed at 5 years in this patient population with advanced heart failure.

Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry.

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.

Left ventricular assist device implantation and concomitant mitral valve surgery: A systematic review and meta-analysis.

BACKGROUND: The management of concomitant valvular lesions in patients undergoing left ventricular assist device (LVAD) implantation remains a topic of debate. This systematic review and meta-analysis aimed to evaluate the existing evidence on postoperative outcomes following LVAD implantation, with and without concomitant MV surgery. METHODS: A systematic database search was conducted as per PRISMA guidelines, of original articles comparing LVAD alone to LVAD plus concomitant MV surgery up to February 2023. The primary outcomes assessed were overall mortality and early mortality, while secondary outcomes included stroke, need for right ventricular assist device (RVAD) implantation, postoperative mitral valve regurgitation, major bleeding, and renal dysfunction. RESULTS: The meta-analysis included 10 studies comprising 32 184 patients. It revealed that concomitant MV surgery during LVAD implantation did not significantly affect overall mortality (OR:0.83; 95% CI: 0.53 to 1.29; p = 0.40), early mortality (OR:1.17; 95% CI: 0.63 to 2.17; p = 0.63), stroke, need for RVAD implantation, postoperative mitral valve regurgitation, major bleeding, or renal dysfunction. These findings suggest that concomitant MV surgery appears not to confer additional benefits in terms of these clinical outcomes. CONCLUSION: Based on the available evidence, concomitant MV surgery during LVAD implantation does not appear to have a significant impact on postoperative outcomes. However, decision-making regarding MV surgery should be individualized, considering patient-specific factors and characteristics. Further research with prospective studies focusing on specific patient populations and newer LVAD devices is warranted to provide more robust evidence and guide clinical practice in the management of valvular lesions in LVAD recipients.

Antibacterial copper-filled TiO2 coating of cardiovascular implants to prevent infective endocarditis-A pilot study.

BACKGROUND: Infective endocarditis (IE) poses a significant health risk, especially in patients with prosthetic heart valves. Despite advances in treatment, mortality rates remain high. This study aims to investigate the antibacterial properties of a copper titanium dioxide (4× Cu-TiO2) coating on cardiovascular implants against Staphylococcus aureus, a common causative agent of IE. METHODS: Titanium oxide carriers functionalized with copper ions were employed as an antibacterial coating for heart and vascular prostheses. The coating's antibacterial efficacy was assessed using S. aureus ATCC 29213. Microscopic evaluations were conducted on both biological and artificial materials. Antibacterial activity was qualitatively assessed via a modified disc diffusion method and quantitatively measured through colony counts in NaCl suspensions. RESULTS: The coating process was successfully applied to all tested cardiovascular prosthetic materials. Qualitative assessments of antibacterial effectiveness revealed an absence of bacterial growth in the area directly beneath the coated valve. Quantitative evaluations showed a significant reduction in bacterial colonization on coated mechanical valves, with 2.95 × 104 CFU per valve, compared to 1.91 × 105 CFU in control valves. CONCLUSIONS: The 4× Cu-TiO2 coating demonstrated promising antibacterial properties against S. aureus, suggesting its potential as an effective strategy for reducing the risk of bacterial colonization of cardiovascular implants. Further studies are needed to assess the longevity of the coating and its efficacy against other pathogens.

Clinical characteristics and long-term outcomes in patients with peripartum cardiomyopathy (PPCM) receiving left ventricular assist devices (LVAD).

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure (HF), presenting with left ventricular (LV) systolic dysfunction either at the end of pregnancy or in the months following delivery. In rare cases, PPCM leads to severe impairment of LV function, refractory cardiogenic shock or advanced HF. LV assist devices (LVAD) have been shown to be a feasible treatment option in advanced HF. However, little is known about long-term outcomes and prognosis of PPCM patients undergoing LVAD implantation. METHODS: A retrospective analysis of data from PPCM patients undergoing LVAD implantation in two tertiary centers with respect to long-term outcomes was performed. RESULTS: Twelve patients of median age 30 (18-39) years were included. Eight patients were experiencing cardiogenic shock (INTERMACS 1) at implantation. Seven patients were implanted within 1 month of their PPCM diagnosis. Median duration of LVAD support was 19 (2-92) months with median follow up of 67 (18-136) months (100% complete). In-hospital and 1-year mortality were 0% and 8.3%, respectively. Two patients died on LVAD support, four patients were successfully bridged to transplantation, two patients are still on LVAD, and four were successfully weaned due to sufficient LV recovery (one died after LV function deteriorated again). CONCLUSION: LVAD treatment of decompensated end-stage PPCM is feasible. Early LVAD provision led to hemodynamic stabilization in our cohort and facilitated safe LV recovery in one third of these young female patients.

Outcomes of modular cable exchange in HeartMate 3 patients versus conventional driveline repair in HeartMate II patients.

BACKGROUND: Driveline (DL) damages are a common difficulty among ventricular assist devices (VAD). Repairing the electrical fibers inside the DL on a running pump is hazardous and requires technical expertise, which is not easily available on site. A new feature of the HeartMate3 (Abbott, U.S.A.) LVAD is a modular driveline that allows an easy exchange of the DL cord. In this report we analyze our experiences with this feature. METHODS: We performed a retrospective analysis of 302 patients who underwent either HeartMate II or HeartMate 3 implantation between February 2004 and September 2021. Patients were screened for driveline faults and need for exchange or repair of driveline or VAD exchange. Documented were baseline characteristics, reasons for DL or VAD exchange, and complications. Follow-up was three months after the procedure. RESULTS: We present a cohort of 302 patients who underwent either HMII (n = 107;35.4%) or HM 3 (n = 195; 64.5%) implantation. Out of those, 40 patients (40/302; 13.2%) required driveline repair (DLRe) or exchange (DLEx). Out of 107 HMII patients, 9 showed severe DL damages (9/107; 8.4%). Six patients (6/9; 66.6%) underwent DLRe, two patients (2/6; 33.3%) required VAD exchange after DLRe, one patient (1/2;50%) experienced emergency VAD exchange after pump stop. The DLRe procedure in the other four patients (4/6; 66.6%) was successful. Due to damage to the internal driveline two patients (2/9; 22.2%) underwent emergency device exchange and one patient (1/9;11.1%) was listed for transplantation. 31 out 195 HM3 patients underwent exchange of the modular DL. In none of the cases, damages of the internal fibers were the reasons for the exchange. In 100% of the cases, damages of the external coating were the reason for DL exchange. In none of the cases, complications occurred after the exchange procedure. CONCLUSIONS: Driveline damages are a habitual, recurrent complication in VAD patients. The exchange of the modular driveline cable of the HM3 is feasible and safe compared to the conventional DL repair in HMII patients. Risky repair attempts and surgical LVAD exchange due to major damages of the electrical fibers can be avoided successfully by the new feature of HM3 driveline.

Microembolic signal monitoring in patients with HeartMate 3 and HeartWare left ventricular assist devices: Association with antithrombotic treatment and cerebrovascular events.

BACKGROUND: In patients with left ventricular assist devices (LVADs), ischemic and hemorrhagic stroke are dreaded complications. Predictive markers for these events are lacking. This study aimed to investigate the prevalence and predictive value of microembolic signals (MES) for stroke, detected by Transcranial Doppler sonography (TCD) in patients with HeartMate 3 (HM 3) or HeartWare (HW). METHODS: A thirty-minute bilateral TCD monitoring of the middle cerebral artery (MCA) was performed in 62 outpatients with LVAD (HM 3 N = 31, HW N = 31) and 31 healthy controls. Prevalence and quantity of MES were investigated regarding clinical and laboratory parameters. Cerebrovascular events (CVE) were recorded on follow-up at 90 and 180 days. RESULTS: MES were detected in six patients with HM 3, three patients with HW, and three controls. Within the LVAD groups, patients on monotherapy with vitamin-K-antagonist (VKA) without antiplatelet therapy were at risk for a higher count of MES (negative binomial regression: VKA: 1; VKA + ASA: Exp(B) = 0.005, 95%CI 0.001-0.044; VKA + clopidogrel: Exp(B) = 0.012, 95%CI 0.002-0.056). There was no association between the presence of MES and CVE or death on follow-up (p > 0.05). CONCLUSION: For the first time, the prevalence of MES was prospectively investigated in a notable outpatient cohort of patients with HM 3 and HW. Despite optimized properties of the latest LVAD, MES remain detectable depending on antithrombotic therapy. No association between MES and CVE could be detected.

The GermAn Laser Lead Extraction RegistrY: GALLERY.

AIMS: The GermAn Laser Lead Extraction RegistrY: GALLERY is a retrospective, national multicentre registry, investigating the safety and efficacy of laser lead extraction procedures in Germany. METHODS AND RESULTS: Twenty-four German centres that are performing laser lead extraction have participated in the registry. All patients, treated with a laser lead extraction procedure between January 2013 and March 2017, were consecutively enrolled. Safety and efficacy of laser lead extraction were investigated. A total number of 2524 consecutive patients with 6117 leads were included into the registry. 5499 leads with a median lead dwell time of 96 (62-141) months were treated. The mean number of treated leads per patient was 2.18 ± 1.02. The clinical procedural success rate was 97.86% and the complete lead removal was observed in 94.85%. Additional extraction tools were used in 6.65% of cases. The rate of procedural failure was 2.14% with lead age ≥10 years being its only predictor. The overall complication rate was 4.32%, including 2.06% major and 2.26% minor complications. Procedure-related mortality was 0.55%. Female sex and the presence of abandoned leads were predictors for procedure-related complications. The all-cause in-hospital mortality was 3.56% with systemic infection being the strongest predictor, followed by age ≥75 years and chronic kidney disease. CONCLUSION: In the GALLERY, a high success- and low procedure-related complication rates have been demonstrated. In multivariate analysis, female sex and the presence of abandoned leads were predictors for procedure-related complications, while the presence of systemic infection, age ≥75 years, and chronic kidney disease were independent predictors for all-cause mortality.

Biocompatibility of an apical ring plug for left ventricular assist device explantation: Results of a feasibility pre-clinical study.

BACKGROUND: Patients receiving left ventricle assist devices (LVADs) as bridge to recovery remain a minority with 1%-5% of LVADs explanted after improvement of myocardial function. Nevertheless, considering the growing population of patients supported with LVADs, an increasing demand of new explantation strategies is expected in the near future. A novel plug for LVAD explantation has been developed and its biocompatibility profile needs to be proved. This study tested the biocompatibility of this novel plug in an in vivo ovine model. METHODS: Six adult Blackhead Persian female sheep received plug implantation on the cardiac apex via minimally invasive approach and were clinically observed up to 90 days. Echocardiography was performed to detect thrombus formation or further plug-related complications. After the observation period, euthanasia was performed and samples including the plug and the surrounding tissues were obtained to be analyzed with correlative light and electron microscopy. Organ necrosis, ischemia and peripheral embolism were investigated. RESULTS: Three animals survived surgery and completed the follow-up time without experiencing clinical complications. Echocardiographic controls excluded the presence of an intracavitary thrombus in the left ventricle (LV). Autopsy confirmed no signs of local infection, LV thrombus or peripheral embolism. Light and electron microscopy revealed an intact epithelium covering a layer of connective tissue on the plug surface facing the heart lumen. CONCLUSIONS: This novel apical plug for LVAD explantation allows for endothelial and connective tissue growth on its ventricular side within 90 days from surgery. Further studies are required to fully demonstrate the biocompatibility of this apical plug and investigate the optimal anticoagulation regimen to be applied after implantation.

Is there a sex gap in outcomes of comparable patients supported with left ventricular assist devices?

OBJECTIVES: Historically, females were described as suffering from worse outcomes after left ventricular assist device (LVAD) implantation. However, females' preoperative conditions are unique, making direct comparisons with males challenging. This study aimed to select through propensity score (PS) matching two preoperatively comparable populations of females and males and test if any real sex-related difference exists regarding survival and adverse events after LVAD implantation. METHODS: This retrospective single-center observational study investigated patients who received LVAD implantation between 2010 and 2018. PS matching was applied to balance preoperative heterogeneity between males and females. Primary endpoint was survival at follow-up. Secondary endpoints included perioperative outcomes and LVAD-related adverse events. RESULTS: 92 fully comparable females(n = 46) and males(n = 46) were selected after PS matching (median age:57 years, min-max:18-75). 26.1% of patients required preoperative mechanical circulatory support. Females needed more intraoperative fresh frozen plasma (p < 0.001) and platelets transfusions (p = 0.008) compared to males, but postoperative outcomes were comparable between groups. In-hospital, 1 and 2-year survival were 78.3%, 69.6% and 65.2%, respectively, with no differences between groups. Survival probability remained comparable up to 8 years of follow-up (p = 0.35). Overall, females showed a higher rate of strokes (p = 0.039) compared to males in the follow-up time. CONCLUSIONS: After reducing preoperative heterogeneity between females and males, survival after LVAD implantation does not differ based on sex. However, differences might exist in terms of higher transfusions and strokes in females. Reducing preoperative sex disparities and developing intraoperative and anticoagulation strategies which acknowledge sex-related variations might help abolishing differences in LVAD outcomes.

Rationale and Initiative of the Impella in Cardiac Surgery (ImCarS) Register Platform.

OBJECTIVES: Cardiac support systems are being used increasingly more due to the growing prevalence of heart failure and cardiogenic shock. Reducing cardiac afterload, intracardiac pressure, and flow support are important factors. Extracorporeal membrane oxygenation (ECMO) and intracardiac microaxial pump systems (Impella) as non-permanent MCS (mechanical circulatory support) are being used increasingly. METHODS: We reviewed the recent literature and developed an international European registry for non-permanent MCS. RESULTS: Life-threatening conditions that are observed preoperatively often include reduced left ventricular function, systemic hypoperfusion, myocardial infarction, acute and chronic heart failure, myocarditis, and valve vitia. Postoperative complications that are commonly observed include severe systemic inflammatory response, ischemia-reperfusion injury, trauma-related disorders, which ultimately may lead to low cardiac output (CO) syndrome and organ dysfunctions, which necessitates a prolonged ICU stay. Choosing the appropriate device for support is critical. The management strategies and complications differ by system. The "heart-team" approach is inevitably needed.However despite previous efforts to elucidate these topics, it remains largely unclear which patients benefit from certain systems, when is the right time to initiate (MCS), which support system is appropriate, what is the optimal level and type of support, which therapeutic additive and supportive strategies should be considered and ultimately, what are the future prospects and therapeutic developments. CONCLUSION: The European cardiac surgical register ImCarS has been established as an IIT with the overall aim to evaluate data received from the daily clinical practice in cardiac surgery. Interested colleagues are cordially invited to join the register. CLINICAL REGISTRATION NUMBER: DRKS00024560. POSITIVE ETHICS VOTE: AZ 246/20 Faculty of Medicine, Justus-Liebig-University-Gießen.

Left ventricular assist device implantation in patients with left ventricular thrombus.

An intra-cavitary left ventricular (LV) thrombus is a relative contraindication to LV assist device (LVAD) implantation based on increased thromboembolic risks. Herein, we present our experience with LVAD patients with or without preoperative diagnosis of LV-thrombus. We retrospectively investigated 563 patients who received LVAD implantation between 2004 and 2018. Diagnosis of LV-thrombus was verified with computed tomography scan, magnetic resonance imaging, echocardiography, or intraoperative LV inspection. The primary endpoint was 30-day survival free of stroke and pump thrombosis. Overall, 72 patients (12.8%) had a diagnosis of LV-thrombus. They were younger (51 years; IQR:41-59), affected by severely reduced ejection fraction (15%; IQR:10-20), more often presenting with dilated cardiomyopathy (61.8%) and INTERMACS profile 1 (33.3%). Preoperative atrial fibrillation was frequent in patients without LV-thrombus (38.9%). Conventional sternotomy was the preferred approach in LV-thrombus patients (77.8%), based on more HMII implantations in these patients (41.7%). Survival free of strokes and pump thrombosis at 30 days was comparable (P = .5751) between patients with (83.3%) or without LV-thrombus (80.9%). LVAD implantation in patients with preoperative LV-thrombus is safe and feasible. When managed through correct diagnostic and intraoperative strategies including accurate inspection of the LV cavity, these patients show similar 30-day outcomes compared to patients without LV-thrombus.

Prophylactic mechanical circulatory support for protected ventricular tachycardia ablation: A meta-analysis of the literature.

Acute hemodynamic decompensation (AHD) during ventricular tachycardia (VT) ablation occurs in about 11% of cases. Prophylactic use of temporary mechanical circulatory support (pro-tMCS) has been applied to prevent AHD during VT ablation, but evidence supporting this practice is still lacking. This systematic review and meta-analysis assessed the procedural characteristics and outcomes of pro-tMCS for VT ablation. PubMed/Medline was screened until February 2020. Articles including adults receiving pro-tMCS for VT ablation were included, and a meta-analysis to compare proMCS and no-tMCS was performed. Primary outcome was in-hospital/30-day mortality. Five observational studies presenting 400 procedures (pro-tMCS: n = 187; no-tMCS: n = 213) were included. Baseline characteristics were comparable between groups. Impella and TandemHeart were used in 86.6% and 13.4% of cases, respectively. In the pro-tMCS group, more VTs were induced (mean difference: 0.52, confidence interval [CI]: 0.26-0.77, P < .0001), and patients remained in VT on average for 24.04 minutes longer (CI: 18.28-29.80, P < .00001). Procedural success was comparable between groups, as was VT recurrence. Pro-tMCS patients had an odds ratio of 0.55 (CI: 0.28-1.05, P = .07) for in-hospital/30-day mortality and 0.55 (CI: 0.32-0.94, P = .03) for mortality at follow-up. Sixty-four percent of no-tMCS patients received rescue tMCS. The most common tMCS-related complications were bleeding events. Pro-tMCS allowed for a prolonged time on VTs and the induction of more VTs. Although these advantages were not associated with differences in procedural success, VT recurrence, or in-hospital/30-day mortality in the overall population, pro-tMCS might improve long-term survival. Further prospective studies are urgently needed to confirm these results.

Flying after left ventricular assist device implantation.

Literature on the air travel activities of patients supported by permanent mechanical assist devices is rare. To the best of our knowledge, no air travel guidelines or fitness prerequisites exist on whether and when ventricular assist device (VAD) patients are allowed to travel by plane after device implantation. In this study, we evaluated the topic of air travel after VAD implantation. This working group aimed to produce a report on air travel passengers supported by VADs, regarding their fitness to fly. Fifty left ventricular assist device (LVAD) patients were surveyed in a worldwide multicenter study. The single survey was performed with a multimethod design, including interviews conducted face-to-face, online, and on phone. Out of 50 patients, 97% described their traveling by aircraft as perfect and uneventful during the flight. Eighty-five percent of the study participants consulted their medical practitioner before the flight. No patient reported the occurrence of a severe condition associated with flying. LVAD alarms, especially low flow alarms, did not occur in any of the devices. Thirty-five percent of the surveyed patients, however, stated a major problem pertaining to the security check procedures at the airport. The results of this study suggest that commercial air travel is safe for stable patients on permanent VAD support and traveling can be resumed securely after VAD implantation. Conscientious preparation by packing necessary devices, fluids, medications, and careful preparation for the airport security check is recommended.

Two-year outcome after implantation of a full magnetically levitated left ventricular assist device: results from the ELEVATE Registry.

AIMS: The ELEVATE Registry was designed to study long-term outcomes with the Heartmate 3 (HM3), a fully magnetically levitated centrifugal ventricular assist device, in a real-world population following CE-mark approval. METHODS AND RESULTS: A total of 540 patients, implanted in Europe and the Middle East were followed in ELEVATE. The registry included 463 patients receiving the HM3 as primary implant (Primary Implant Cohort), 19 patients underwent a pump upgrade from another device (Pump Exchange Cohort) and 58 patients who had experienced an outcome before having the possibility to sign the Informed Consent, for which only outcome data were collected (Anonymized Cohort). Data collection included demographics, survival, adverse events, EQ-5D Visual Analog Score quality of life (EQ-5D VAS QOL) questionnaire, and 6-min walk distance (6MWD). Mean age was 55.6 ± 11.7 years (89% male, 48% ischaemic cardiomyopathy). Seventy per cent of patients were in INTERMACS Profile 1-3 and 12.7% were on temporary mechanical circulatory support. Primary Implant Cohort survival was 83% after 2 years. In the Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Primary Implant Cohort, strokes were observed in 10.2%, gastrointestinal bleedings in 9.7%, pump thrombosis in 1.5%, and outflow graft twists in 3.5%. Heartmate 3 implantation resulted in a significant and sustained improvement of functional capacity and QOL. CONCLUSION: In a real-world population, cohort implanted with the HM3 left ventricular assist device we demonstrate good long-term survival, sustained improvement of functional capacity, and low rates of adverse events (including pump thrombosis). CLINICALTRIALS.GOV IDENTIFIER: NCT02497950.

Targeting muscle-enriched long non-coding RNA H19 reverses pathological cardiac hypertrophy.

AIMS: Pathological cardiac remodelling and subsequent heart failure represents an unmet clinical need. Long non-coding RNAs (lncRNAs) are emerging as crucial molecular orchestrators of disease processes, including that of heart diseases. Here, we report on the powerful therapeutic potential of the conserved lncRNA H19 in the treatment of pathological cardiac hypertrophy. METHOD AND RESULTS: Pressure overload-induced left ventricular cardiac remodelling revealed an up-regulation of H19 in the early phase but strong sustained repression upon reaching the decompensated phase of heart failure. The translational potential of H19 is highlighted by its repression in a large animal (pig) model of left ventricular hypertrophy, in diseased human heart samples, in human stem cell-derived cardiomyocytes and in human engineered heart tissue in response to afterload enhancement. Pressure overload-induced cardiac hypertrophy in H19 knock-out mice was aggravated compared to wild-type mice. In contrast, vector-based, cardiomyocyte-directed gene therapy using murine and human H19 strongly attenuated heart failure even when cardiac hypertrophy was already established. Mechanistically, using microarray, gene set enrichment analyses and Chromatin ImmunoPrecipitation DNA-Sequencing, we identified a link between H19 and pro-hypertrophic nuclear factor of activated T cells (NFAT) signalling. H19 physically interacts with the polycomb repressive complex 2 to suppress H3K27 tri-methylation of the anti-hypertrophic Tescalcin locus which in turn leads to reduced NFAT expression and activity. CONCLUSION: H19 is highly conserved and down-regulated in failing hearts from mice, pigs and humans. H19 gene therapy prevents and reverses experimental pressure-overload-induced heart failure. H19 acts as an anti-hypertrophic lncRNA and represents a promising therapeutic target to combat pathological cardiac remodelling.

A novel screening tool to unmask potential interference between S-ICD and left ventricular assist device.

INTRODUCTION: In patients with a left ventricular assist device (LVAD), the subcutaneous implantable cardioverter-defibrillator (S-ICD) can be an alternative to transvenous ICD systems due to reduced risk of systemic infection, which could lead to extraction of the ICD as well as the LVAD. S-ICD eligibility is lower in patients with LVAD than in patients with end-stage heart failure without LVAD. Several reports have shown inappropriate S-ICD therapy in the coexistence of LVAD and S-ICD. The aim of the present study was to evaluate S-ICD eligibility in patients with LVAD using the established electrocardiogram (ECG)-based screening test as well as a novel device-based screening test to identify potentially inappropriate S-ICD sensing in this specific patient cohort. METHODS AND RESULTS: The present study included 115 patients implanted with an LVAD. The standard ECG-based screening test and a novel device-based screening test were performed in all patients. Eighty patients (70%) were eligible for S-ICD therapy with the standard ECG-based screening test. Performance of the novel device-based screening test identified device-device interference in 14 of these 80 patients (12%). CONCLUSION: Using a novel extended device-based S-ICD screening method, a small number of patients with LVAD deemed eligible for S-ICD with the standard ECG-based screening test exhibit device-device interference. Careful S-ICD screening should be performed in patients with LVAD, who are candidates for S-ICD therapy, to prevent inappropriate sensing or ICD therapy.

Predictors of Physical Capacity 6 Months After Implantation of a Full Magnetically Levitated Left Ventricular Assist Device: An Analysis From the ELEVATE Registry.

BACKGROUND: In patients with a continuous-flow left ventricular assist device, preimplant predictors of poor physical performance are not well-described. We aimed to identify predictors of inability to walk more than 300 m on 6-minute walk test (6MWT) 6 months after HeartMate 3 implantation. METHODS AND RESULTS: Using data from the European Registry of Patients Implanted With a Full Magnetically Levitated LVAD, patients with available 6MWT at 6 months after implantation were included (N = 194) and grouped according to 6MWT distance (6MWD) of >300 m (n = 150) or 6MWD of <300 m (n = 44). Patients walking <300 m were older (60 ± 10 vs 52 ± 12 years; P < .001), more often New York Heart Association functional class IV (63% vs 42%; P = .03), and more often had type 2 diabetes (43% vs 17%; P < .001) at implantation. Atrial fibrillation was seen in 57% in those with a 6MWT of <300 m vs 31% in those walking longer (P < .002). Further, hemoglobin and estimated glomerular filtration rate was lower in those walking <300 m (both P < .01). In multivariable regression analysis, independent predictors of a 6MWD of <300 m were: atrial fibrillation (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.12-8.67), older age (OR for 10-year increment, 2.81; 95% CI, 1.55-5.07), New York Heart Association functional class IV (OR, 3.37; 95% CI, 1.27-8.98), and Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2 (OR, 6.53; 95% CI, 1.92-22.19). CONCLUSIONS: Six months after HeartMate 3 implantation, 77% of patients walked >300 meters in 6 minutes. Apart from age and measures of heart failure severity, atrial fibrillation at implantation is an independent predictor of low 6MWD at 6 months after implantation.

Out of hospital management of LVAD patients during COVID-19 outbreak.

Coronavirus disease 2019 (COVID-19) is a pandemic touching thousands of people all around the world. Patients supported with left ventricular assist devices (LVADs) are affected by long-standing cardiovascular diseases and subjected to variations of the normal cardiovascular physiology, thus requiring an even closer monitoring during the COVID-19 outbreak. Nevertheless, the COVID-19 pandemic led to a drastic reduction in routine clinical activities and a consequent risk of looser connections between LVAD patients and their referring center. Potential deleterious effects of such a situation can be a delayed recognition of LVAD-related complications, misdiagnosis of COVID-19, and impaired social and psychological well-being for patients and families. As one of the largest LVAD programs worldwide, we designed a sustainable and enforceable telemonitoring algorithm which can be easily adapted to every LVAD center so as to maintain optimal quality of care for LVAD patients during the COVID-19 pandemic.

Improved aftercare in LVAD patients: Development and feasibility of a smartphone application as a first step for telemonitoring.

For the success of the treatment with a left ventricular assist device (LVAD), both adequate self-management by the patient and an optimum level of support from the implanting hospital are crucial. A smartphone application has recently been developed within the framework of a European research project for the close monitoring of LVAD patients in order to improve upon their current aftercare situation. Using this new tool, different relevant parameters (eg, weight, international normalized ratio [INR], medication, LVAD parameters, symptoms, and photos of the driveline exit) can be sent daily or as required to a corresponding clinical application at the hospital for evaluation. The objective of this study was to monitor the functionality, acceptance, and usability of this smartphone application in LVAD patients. Prospective single-center study: in total, 13 patients (60 ± 7 years, 92% male, 1027 ± 653 days after LVAD implantation) were requested to test the application for approx. 4 weeks. At the end of the study, all entered data were evaluated and the patients were questioned regarding the acceptance and the usability. During the study period of mean 34 ± 8 days, a total of 453 data records (mean 35 ± 7 per patient) arrived at the hospital. In addition, a total of 19 photos of the driveline exit site were also sent via smartphone. The clinical application registered a total of 160 conspicuities. These comprised 126 INR deviations (target range 2.3-2.8) and 34 symptoms (mainly nosebleeds). The smartphone application functioned reliably, was well received by the patients and was graded highly for acceptance and usability. The results show that smartphone applications can definitely be used to improve aftercare in LVAD therapy in selected patients. Long-term studies are now needed to investigate the extent to which complications can be prevented, healthcare costs reduced, and quality of life increased.