2019 EACTS Expert Consensus on long-term mechanical circulatory support

Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many-sometimes contradictory-observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): first annual report

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS) was founded on 10 December 2009 with the initiative of Roland Hetzer (Deutsches Herzzentrum Berlin, Berlin, Germany) and Jan Gummert (Herz- und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen, Germany) with 15 other founding international members. It aims to promote scientific research to improve care of end-stage heart failure patients with ventricular assist device or a total artificial heart as long-term mechanical circulatory support. Likewise, the organization aims to provide and maintain a registry of device implantation data and long-term follow-up of patients with mechanical circulatory support. Hence, EUROMACS affiliated itself with Dendrite Clinical Systems Ltd to offer its members a software tool that allows input and analysis of patient clinical data on a daily basis. EUROMACS facilitates further scientific studies by offering research groups access to any available data wherein patients and centres are anonymized. Furthermore, EUROMACS aims to stimulate cooperation with clinical and research institutions and with peer associations involved to further its aims. EUROMACS is the only European-based Registry for Patients with Mechanical Circulatory Support with rapid increase in institutional and individual membership. Because of the expeditious data input, the European Association for Cardiothoracic Surgeons saw the need to optimize the data availability and the significance of the registry to improve care of patients with mechanical circulatory support and its potential contribution to scientific intents; hence, the beginning of their alliance in 2012. This first annual report is designed to provide an overview of EUROMACS' structure, its activities, a first data collection and an insight to its scientific contributions

The combined human genotype of truncating TTN\it TTN and RBM20\it RBM20 mutations is associated with severe and early onset of dilated cardiomyopathy

A major cause of heart failure is cardiomyopathies, with dilated cardiomyopathy (DCM) as the most common form. Over 40 genes are linked to DCM, among them $\it TTN$ and $\it RBM20$. Next Generation Sequencing in clinical DCM cohorts revealed truncating variants in $\it TTN$ ($\it TTN$tv), accounting for up to 25% of familial DCM cases. Mutations in the cardiac splicing factor RNA binding motif protein 20 ($\it RBM20$) are also known to be associated with severe cardiomyopathies. $\it TTN$ is one of the major $\it RBM20$ splicing targets. Most of the pathogenic $\it RBM20$ mutations are localized in the highly conserved arginine serine rich domain (RS), leading to a cytoplasmic mislocalization of mutant $\it RBM20$. Here, we present a patient with an early onset DCM carrying a combination of (likely) pathogenic $\it TTN$ and $\it RBM20$ mutations. We show that the splicing of $\it RBM20$ target genes is affected in the mutation carrier. Furthermore, we reveal $\it RBM20$ haploinsufficiency presumably caused by the frameshift mutation in $\it RBM20$

2019 EACTS Expert Consensus on long-term mechanical circulatory support

Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many-sometimes contradictory-observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device

A multicenter evaluation of external outflow graft obstruction with a fully magnetically levitated left ventricular assist device

Background: The HeartMate 3 (HM 3; Abbott) left ventricular assist device (LVAD) has improved hemocompatibility-related adverse outcomes. In sporadic cases, external compression of the outflow graft causing obstruction (eOGO) can result from substance accumulation between the outflow graft and its bend relief. We sought to evaluate the prevalence, course, and clinical implications of eOGO in an international study. Methods: A multicenter retrospective analysis of HM 3 LVADs implanted between November 2014 and April 2021 (n = 2108) was conducted across 17 cardiac centers in 8 countries. We defined eOGO as obstruction >25% in the cross-sectional area in imaging (percutaneous angiography, computed tomography, or intravascular ultrasound). The prevalence and annual incidence were calculated. Serious adverse events and outcomes (death, transplantation, or device exchange) were analyzed for eOGO cases. Results: Of 2108 patients, 62 were diagnosed with eOGO at a median LVAD support duration of 953 (interquartile range, 600-1267) days. The prevalence of eOGO was 3.0% and the incidence at 1, 2, 3, 4, and 5 years of support was 0.6%, 2.8%, 4.0%, 5.2%, and 9.1%, respectively. Of 62 patients, 9 were observed, 27 underwent surgical revision, 15 underwent percutaneous stent implantation, 8 received a heart transplant, and 2 died before intervention. One patient underwent surgical revision and later stent implantation. The mortality with therapeutic intervention was 9/53 (17.0%). Conclusions: Although uncommon, HM 3 LVAD-supported patients might develop eOGO with an increasing incidence after 1 year of support. Although engineering efforts to reduce this complication are under way, clinicians must maintain a focus on early detection and remain vigilant

Spatial multi-omic map of human myocardial infarction

Myocardial infarction is a leading cause of death worldwide1. Although advances have been made in acute treatment, an incomplete understanding of remodelling processes has limited the effectiveness of therapies to reduce late-stage mortality2. Here we generate an integrative high-resolution map of human cardiac remodelling after myocardial infarction using single-cell gene expression, chromatin accessibility and spatial transcriptomic profiling of multiple physiological zones at distinct time points in myocardium from patients with myocardial infarction and controls. Multi-modal data integration enabled us to evaluate cardiac cell-type compositions at increased resolution, yielding insights into changes of the cardiac transcriptome and epigenome through the identification of distinct tissue structures of injury, repair and remodelling. We identified and validated disease-specific cardiac cell states of major cell types and analysed them in their spatial context, evaluating their dependency on other cell types. Our data elucidate the molecular principles of human myocardial tissue organization, recapitulating a gradual cardiomyocyte and myeloid continuum following ischaemic injury. In sum, our study provides an integrative molecular map of human myocardial infarction, represents an essential reference for the field and paves the way for advanced mechanistic and therapeutic studies of cardiac disease