Arrhythmogenic Left Ventricular Mass as the Initial Presentation of Cardiac Sarcoidosis.

Cardiac tumors of the left ventricle are rare, and cardiac magnetic resonance is the preferred imaging tool for evaluation given superior tissue characterization. We present a case of a patient with arrhythmia and left ventricular mass that was ultimately diagnosed with cardiac sarcoidosis, reminding us that tissue is the issue.

Clinical Course of Patients in Cardiogenic Shock Stratified by Phenotype.

Background: Cardiogenic shock (CS) patients remain at 30% to 60% in-hospital mortality despite therapeutic innovations. Heterogeneity of CS has complicated clinical trial design. Recently, 3 distinct CS phenotypes were identified in the CSWG (Cardiogenic Shock Working Group) registry version 1 (V1) and external cohorts: I, "noncongested;" II, "cardiorenal;" and III, "cardiometabolic" shock.

Criteria for Defining Stages of Cardiogenic Shock Severity.

Background: Risk-stratifying patients with cardiogenic shock (CS) is a major unmet need. The recently proposed Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks uniform criteria defining each stage.

Objectives: The purpose of this study was to test parameters that define SCAI stages and explore their utility as predictors of in-hospital mortality in CS.

Device profile of the Impella 5.0 and 5.5 system for mechanical circulatory support for patients with cardiogenic shock: overview of its safety and efficacy.

Introduction: Trans-valvular micro-axial flow pumps such as Impella are increasingly utilized in patients with cardiogenic shock [CS]. A number of different Impella devices are now available providing a wide range of cardiac output. Among these, the Impella 5.

Right Ventricular Dysfunction Is Common and Identifies Patients at Risk of Dying in Cardiogenic Shock.

Background: Understanding the prognostic impact of right ventricular dysfunction (RVD) in cardiogenic shock (CS) is a key step toward rational diagnostic and treatment algorithms and improved outcomes. Using a large multicenter registry, we assessed (1) the association between hemodynamic markers of RVD and in-hospital mortality, (2) the predictive value of invasive hemodynamic assessment incorporating RV evaluation, and (3) the impact of RVD severity on survival in CS.

Methods And Results: Inpatients with CS owing to acute myocardial infarction (AMI) or heart failure (HF) between 2016 and 2019 were included.

Impact of Age on Outcomes in Patients With Cardiogenic Shock.

Advanced age is associated with poor outcomes in cardiovascular emergencies. We sought to determine the association of age, use of support devices and shock severity on mortality in cardiogenic shock (CS). Characteristics and outcomes in CS patients included in the Cardiogenic Shock Work Group (CSWG) registry from 8 US sites between 2016 and 2019 were retrospectively reviewed.

Clinical Outcomes Associated With Acute Mechanical Circulatory Support Utilization in Heart Failure Related Cardiogenic Shock.

Background: Cardiogenic shock occurring in the setting of advanced heart failure (HF-CS) is increasingly common. However, recent studies have focused almost exclusively on acute myocardial infarction-related CS. We sought to define clinical, hemodynamic, metabolic, and treatment parameters associated with clinical outcomes among patients with HF-CS, using data from the Cardiogenic Shock Working Group registry.

Estimation of Stressed Blood Volume in Patients With Cardiogenic Shock From Acute Myocardial Infarction and Decompensated Heart Failure.

Background: Sympathetically mediated redistribution of blood from the unstressed venous reservoir to the hemodynamically active stressed compartment is thought to contribute to congestion in cardiogenic shock (CS). We used a novel computational method to estimate stressed blood volume (SBV) in CS and assess its relationship with clinical outcomes.

Methods And Results: Hemodynamic parameters including estimated SBV (eSBV) were compared among patients from the Cardiogenic Shock Working Group registry with a complete set of hemodynamic data.

Aortix™: a novel intra-aortic entrainment pump.

Use of short-term mechanical circulatory support pumps for cardiogenic shock, decompensated heart failure and high-risk coronary intervention is growing. The Aortix™ device (Procyrion, TX, USA) is the first axial-flow pump positioned in the aorta and is designed to provide short-term hemodynamic support. This review discusses the field of continuous flow aortic pumps and focuses specifically on emerging preclinical and clinical data supporting the development of these technologies.

Complete Hemodynamic Profiling With Pulmonary Artery Catheters in Cardiogenic Shock Is Associated With Lower In-Hospital Mortality.

Objectives: The purpose of this study was to investigate the association between obtaining hemodynamic data from early pulmonary artery catheter (PAC) placement and outcomes in cardiogenic shock (CS).

Background: Although PACs are used to guide CS management decisions, evidence supporting their optimal use in CS is lacking.

Methods: The Cardiogenic Shock Working Group (CSWG) collected retrospective data in CS patients from 8 tertiary care institutions from 2016 to 2019.

Central Venous Pressure and Clinical Outcomes During Left-Sided Mechanical Support for Acute Myocardial Infarction and Cardiogenic Shock.

Right ventricular failure (RVF) is associated with increased mortality among patients receiving left ventricular mechanical circulatory support (LV-MCS) for cardiogenic shock and requires prompt recognition and management. Increased central venous pressure (CVP) is an indicator of potential RVF. We studied whether elevated CVP during LV-MCS for acute myocardial infarction complicated by cardiogenic shock is associated with higher mortality.

The science of safety: complications associated with the use of mechanical circulatory support in cardiogenic shock and best practices to maximize safety.

Acute mechanical circulatory support (MCS) devices are widely used in cardiogenic shock (CS) despite a lack of high-quality clinical evidence to guide their use. Multiple devices exist across a spectrum from modest to complete support, and each is associated with unique risks. In this review, we summarize existing data on complications associated with the three most widely used acute MCS platforms: the intra-aortic balloon pump (IABP), Impella systems, and veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

Clinical trials of acute mechanical circulatory support in cardiogenic shock and high-risk percutaneous coronary intervention.

Purpose Of Review: Acute mechanical circulatory support devices have become widely used in cardiogenic shock and high-risk percutaneous coronary intervention (PCI) but there remains significant controversy over the evidence supporting their use and the specific roles of various devices. In this review, we summarize major recent studies and identify key areas of future investigation.

Recent Findings: In cardiogenic shock, uncontrolled single arm studies emphasizing early mechanical circulatory support (MCS) have showed promising results, but randomized trials have either been stopped prematurely or enrolled patients with advanced shock unlikely to benefit from MCS.

A Comprehensive, CRISPR-based Functional Analysis of Essential Genes in Bacteria.

Essential gene functions underpin the core reactions required for cell viability, but their contributions and relationships are poorly studied in vivo. Using CRISPR interference, we created knockdowns of every essential gene in Bacillus subtilis and probed their phenotypes. Our high-confidence essential gene network, established using chemical genomics, showed extensive interconnections among distantly related processes and identified modes of action for uncharacterized antibiotics.

Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds.

Eukaryotic cells execute complex transcriptional programs in which specific loci throughout the genome are regulated in distinct ways by targeted regulatory assemblies. We have applied this principle to generate synthetic CRISPR-based transcriptional programs in yeast and human cells. By extending guide RNAs to include effector protein recruitment sites, we construct modular scaffold RNAs that encode both target locus and regulatory action.

Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation.

While the catalog of mammalian transcripts and their expression levels in different cell types and disease states is rapidly expanding, our understanding of transcript function lags behind. We present a robust technology enabling systematic investigation of the cellular consequences of repressing or inducing individual transcripts. We identify rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%-99% knockdown with minimal off-target effects, and activators (CRISPRa) to endogenous genes via endonuclease-deficient Cas9.

CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes.

The genetic interrogation and reprogramming of cells requires methods for robust and precise targeting of genes for expression or repression. The CRISPR-associated catalytically inactive dCas9 protein offers a general platform for RNA-guided DNA targeting. Here, we show that fusion of dCas9 to effector domains with distinct regulatory functions enables stable and efficient transcriptional repression or activation in human and yeast cells, with the site of delivery determined solely by a coexpressed short guide (sg)RNA.

N-terminal phosphorylation of p60 katanin directly regulates microtubule severing.

Proteins of the AAA (ATPases associated with various cellular activities) family often have complex modes of regulation due to their central position in important cellular processes. p60 katanin, an AAA protein that severs and depolymerizes microtubules, is subject to multiple modes of regulation including a phosphorylation in the N-terminal domain involved in mitotic control of severing. Phosphorylation decreases severing activity in Xenopus egg extracts and is involved in controlling spindle length.