scholarly journals Arrhythmogenic Cardiomyopathy—Current Treatment and Future Options

2021 ◽  
Vol 10 (13) ◽  
pp. 2750
Author(s):  
Federico Migliore ◽  
Giulia Mattesi ◽  
Alessandro Zorzi ◽  
Barbara Bauce ◽  
Ilaria Rigato ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
Ventricular Dysfunction ◽  
Original Description ◽  
Current Treatment ◽  
Muscle Disease ◽  
Arrhythmogenic Cardiomyopathy ◽  
The Right ◽  
Selection Of Patients ◽  
Selection Of ◽  
Myocardial Lesions

Arrhythmogenic cardiomyopathy (ACM) is an inheritable heart muscle disease characterised pathologically by fibrofatty myocardial replacement and clinically by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Although, in its original description, the disease was believed to predominantly involve the right ventricle, biventricular and left-dominant variants, in which the myocardial lesions affect in parallel or even mostly the left ventricle, are nowadays commonly observed. The clinical management of these patients has two main purposes: the prevention of SCD and the control of arrhythmic and heart failure (HF) events. An implantable cardioverter defibrillator (ICD) is the only proven lifesaving treatment, despite significant morbidity because of device-related complications and inappropriate shocks. Selection of patients who can benefit the most from ICD therapy is one of the most challenging issues in clinical practice. Risk stratification in ACM patients is mostly based on arrhythmic burden and ventricular dysfunction severity, although other clinical features resulting from electrocardiogram and imaging modalities such as cardiac magnetic resonance may have a role. Medical therapy is crucial for treatment of VAs and the prevention of negative ventricular remodelling. In this regard, the efficacy of novel anti-HF molecules and drugs acting on the inflammatory pathway in patients with ACM is, to date, unknown. Catheter ablation represents an effective strategy to treat ventricular tachycardia relapses and recurrent ICD shocks. The present review will address the current strategies for prevention of SCD and treatment of VAs and HF in patients with ACM.

scholarly journals Review. Anticoagulant Therapy in Sepsis. The Importance of Timing

2017 ◽  
Vol 3 (2) ◽  
pp. 63-69 ◽  
Author(s):  
Ecaterina Scarlatescu ◽  
Dana Tomescu ◽  
Sorin Stefan Arama
Keyword(s):  
Anticoagulant Therapy ◽  
Coagulation Activation ◽  
Proper Selection ◽  
Beneficial Effects ◽  
Patient Heterogeneity ◽  
The Difference ◽  
The Right ◽  
Harmful Effects ◽  
Selection Of Patients ◽  
Selection Of

Abstract Sepsis associated coagulopathy is due to the inflammation-induced activation of coagulation pathways concomitant with dysfunction of anticoagulant and fibrinolytic systems, leading to different degrees of haemostasis dysregulation. This response is initially beneficial, contributing to antimicrobial defence, but when control is lost coagulation activation leads to widespread microvascular thrombosis and subsequent organ failure. Large clinical trials of sepsis-related anticoagulant therapies failed to show survival benefits, but posthoc analysis of databases and several smaller studies showed beneficial effects of anticoagulants in subgroups of patients with early sepsis-induced disseminated intravascular coagulation. A reasonable explanation could be the difference in timing of anticoagulant therapy and patient heterogeneity associated with large trials. Proper selection of patients and adequate timing are required for treatment to be successful. The time when coagulation activation changes from advantageous to detrimental represents the right moment for the administration of coagulation-targeted therapy. In this way, the defence function of the haemostatic system is preserved, and the harmful effects of overwhelming coagulation activation are avoided.

scholarly journals Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy inKRASWild-Type Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Tze-Kiong Er ◽  
Chih-Chieh Chen ◽  
Luis Bujanda ◽  
Marta Herreros-Villanueva
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Genetic Determinants ◽  
Secondary Resistance ◽  
Epidermal Growth ◽  
The Right ◽  
Colorectal Cancer Patients ◽  
Selection Of Patients ◽  
Selection Of

Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit.KRASmutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction ofKRASwild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation ofBRAF,NRAS,PIK3CA, andPTENstatus could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.

scholarly journals Low QRS voltage and atrial fibrillation precluding implantation of a subcutaneous implantable cardioverterdefibrillator in a patient with arrhythmogenic cardiomyopathy

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Peter C. Kahr ◽  
Jan Steffel ◽  
Alexander Breitenstein ◽  
Thomas Wolber ◽  
Laurent M. Haegeli ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ventricular Arrhythmias ◽  
Vascular System ◽  
Persistent Atrial Fibrillation ◽  
Hereditary Disease ◽  
Fatty Tissue ◽  
Arrhythmogenic Cardiomyopathy ◽  
Foreign Material ◽  
Icd Implantation ◽  
The Right

Arrhythmogenic cardiomyopathy (AC) is a rare mostly hereditary disease, in which fibro-fatty tissue replaces cardiomyocytes. Typically, the first alterations of the disease can be encountered in the epicardium of the right ventricle in adolescent patients. From there, the disease usually progresses over time. Besides the development of heart failure, the clinical significance of the disease is determined by the predisposition to potentially lethal ventricular arrhythmias. Hence, a majority of patients with AC require an implantable cardioverter-defibrillator (ICD) to be protected from sudden cardiac death. A recently developed alternative to transvenous systems are subcutaneous ICDs (S-ICD), associated with a lower risk of device-related complications such as endocarditis since no foreign material is implanted within the heart and vascular system. In this report, we describe and discuss our experience with the implantation of a S-ICD in a patient with AC, who had low QRS voltage and persistent atrial fibrillation precluding successful S-ICD implantation, as well as the challenges encountered during subsequent transvenous lead implantation.

scholarly journals Role of Exercise as a Modulating Factor in Arrhythmogenic Cardiomyopathy

2021 ◽  
Vol 23 (6) ◽  
Author(s):  
Alessandro Zorzi ◽  
Alberto Cipriani ◽  
Riccardo Bariani ◽  
Kalliopi Pilichou ◽  
Domenico Corrado ◽  
...  
Keyword(s):  
Physical Activity ◽  
Gene Mutation ◽  
Ventricular Arrhythmias ◽  
Muscle Disease ◽  
Moderate Intensity ◽  
Moderate Physical Activity ◽  
Fatty Tissue ◽  
Arrhythmogenic Cardiomyopathy ◽  
Mutation Carriers

Abstract Purpose of Review The review addresses the role of exercise in triggering ventricular arrhythmias and promoting disease progression in arrhythmogenic cardiomyopathy (AC) patients and gene-mutation carriers, the differential diagnosis between AC and athlete’s heart and current recommendations on exercise activity in AC. Recent Findings AC is an inherited heart muscle disease caused by genetically defective cell-to-cell adhesion structures (mainly desmosomes). The pathophysiological hallmark of the disease is progressive myocyte loss and replacement by fibro-fatty tissue, which creates the substrates for ventricular arrhythmias. Animal and human studies demonstrated that intense exercise, but not moderate physical activity, may increase disease penetrance, worsen the phenotype, and favor life-threatening ventricular arrhythmias. It has been proposed that in some individuals prolonged endurance sports activity may in itself cause AC (so-called exercise-induced AC). Summary The studies agree that intense physical activity should be avoided in patients with AC and healthy gene-mutation carriers. However, low-to-moderate intensity exercise does not appear detrimental and these patients should not be entirely deprived from the many health benefits of physical activity.

scholarly journals The role of rational immunotherapy for renal cell carcinoma

2003 ◽  
Vol 11 (1) ◽  
pp. 17-19
Author(s):  
Svetlana Salma
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Combined Therapy ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Rational Approach ◽  
Selection Of Patients ◽  
Selection Of

Metastases to distant organs are the principal cause of death from renal cell carcinoma (RCC). No commonly accepted therapy is available for disseminated RCC at present. The rationale for immunotherapy of RCC is based on the fact that there is no other therapy for advanced cases. Biologic therapies are the only current treatment modalities that have produced promising therapeutic results in metastatic RCC (mRCC). Therapy with cytokines usually has typical and sometimes severe side effects. Response rates and toxicity were higher with combined therapy. The administration of cytokines that augment the function of the immune system can be accomplished safely and without toxicity, provided a rational approach is used. The toxic effects that are frequently observed with combined therapy emphasize the need for careful selection of patients.

scholarly journals Clinical trial design for progressive MS trials

2017 ◽  
Vol 23 (12) ◽  
pp. 1642-1648 ◽  
Author(s):  
Matteo Pardini ◽  
Gary Cutter ◽  
Maria Pia Sormani
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Trial Design ◽  
Clinical Trial Design ◽  
Progressive Multiple Sclerosis ◽  
Phase 2 ◽  
The Right ◽  
Selection Of Patients ◽  
Selection Of

The design of clinical trials is a key aspect to maximizing the possibility to detect a treatment effect. This fact is particularly challenging in progressive multiple sclerosis (PMS) studies due to the uncertainty about the right target and/or outcome in phase-2 studies. The aim of this review is to evaluate the current challenges facing the design of clinical trials for PMS. The selection of patients, the instrumental and clinical outcomes that can be used in PMS trials, and issues in their design will be covered in this report.

scholarly journals Tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors are the cellular source of fibrofatty infiltration in arrhythmogenic cardiomyopathy

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 141 ◽  
Author(s):  
Ben Paylor ◽  
Justin Fernandes ◽  
Bruce McManus ◽  
Fabio Rossi
Keyword(s):  
Ventricular Arrhythmias ◽  
Pathological Process ◽  
Mesenchymal Progenitor Cells ◽  
Arrhythmogenic Cardiomyopathy ◽  
Mesenchymal Progenitors ◽  
Increased Risk ◽  
Cellular Source ◽  
Myocardial Dystrophy ◽  
The Right

Arrhythmogenic cardiomyopathy (AC) is a disease of the heart involving myocardial dystrophy leading to fibrofatty scarring of the myocardium and is associated with an increased risk of both ventricular arrhythmias and sudden cardiac death. It often affects the right ventricle but may also involve the left. Although there has been significant progress in understanding the role of underlying desmosomal genetic defects in AC, there is still a lack of data regarding the cellular processes involved in its progression. The development of cardiac fibrofatty scarring is known to be a principal pathological process associated with ventricular arrhythmias, and it is vital that we elucidate the role of various cell populations involved in the disease if targeted therapeutics are to be developed. The known role of mesenchymal progenitor cells in the reparative process of both the heart and skeletal muscle has provided inspiration for the identification of the cellular basis of fibrofatty infiltration in AC. Here we hypothesize that reparative processes triggered by myocardial degeneration lead to the differentiation of tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors into adipocytes and fibroblasts, which compose the fibrofatty lesions characteristic of AC.

scholarly journals Recent Treatments of Interstitial Lung Disease with Systemic Sclerosis

2015 ◽  
Vol 9s1 ◽  
pp. CCRPM.S23315 ◽  
Author(s):  
Hidekata Yasuoka
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Treatment Options ◽  
Immune Dysfunction ◽  
Pulmonary Involvement ◽  
Current Treatment ◽  
Microvascular Injury ◽  
Selection Of Patients ◽  
Selection Of

Systemic sclerosis (SSc) is a disorder characterized by immune dysfunction, microvascular injury, and fibrosis. Organ involvement in patients with SSc is variable; however, pulmonary involvement occurs in up to 90% of patients with SSc. Interstitial lung disease (ILD) is a major cause of mortality and, thus, a major determinant in the prognosis of patients with SSc. This review summarizes current findings about the characteristics of ILD in patients with SSc, selection of patients with SSc-ILD who are candidates for the treatment, and current treatment options.

scholarly journals Epicardial ablation of ventricular tachycardia in a patient with arrhythmogenic right ventricular dysplasia after failed conventional endocardial ablation: A case for remote navigation with functional image integration

2017 ◽  
Vol 2016 (4) ◽  
Author(s):  
Sabine Ernst ◽  
Karine Roy ◽  
Eric Lim ◽  
Glyn Thomas
Keyword(s):  
Ventricular Tachycardia ◽  
Right Ventricular ◽  
Ventricular Arrhythmias ◽  
Arrhythmogenic Right Ventricular Dysplasia ◽  
Left Ventricular ◽  
Muscle Disease ◽  
Remote Magnetic Navigation ◽  
Right Ventricular Dysplasia ◽  
Functional Image ◽  
The Right

Arrhythmogenic right ventricular dysplasia (ARVD) is an inheritable heart muscle disease that predominantly affects the right ventricle (RV) and predisposes to ventricular arrhythmias and sudden cardiac death (SCD)1. The natural history is predominantly related to ventricular electric instability which may lead to arrhythmic SCD, mostly in young people and athletes2,3, but may progress with significant RV muscle disease and left-ventricular (LV) involvement and can result in right or biventricular heart failure4. We report on a 54-year-old male with ARVD who underwent an epicardial ventricular tachycardia (VT) ablation using remote magnetic navigation (RMN) after functional imaging from a nuclear perfusion study was fused with a 3D segmentation from computed tomography (CT) imaging. 

scholarly journals Arrhythmogenic Left Ventricular Cardiomyopathy: Genotype-Phenotype Correlations and New Diagnostic Criteria

2021 ◽  
Vol 10 (10) ◽  
pp. 2212
Author(s):  
Giulia Mattesi ◽  
Alberto Cipriani ◽  
Barbara Bauce ◽  
Ilaria Rigato ◽  
Alessandro Zorzi ◽  
...  
Keyword(s):  
Task Force ◽  
Current Knowledge ◽  
Critical Evaluation ◽  
Original Description ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Muscle Disease ◽  
Dominant Form ◽  
Consensus Document ◽  
The Right

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease characterized by loss of ventricular myocardium and fibrofatty replacement, which predisposes to scar-related ventricular arrhythmias and sudden cardiac death, particularly in the young and athletes. Although in its original description the disease was characterized by an exclusive or at least predominant right ventricle (RV) involvement, it has been demonstrated that the fibrofatty scar can also localize in the left ventricle (LV), with the LV lesion that can equalize or even overcome that of the RV. While the right-dominant form is typically associated with mutations in genes encoding for desmosomal proteins, other (non-desmosomal) mutations have been showed to cause the biventricular and left-dominant variants. This has led to a critical evaluation of the 2010 International Task Force criteria, which exclusively addressed the right phenotypic manifestations of ACM. An International Expert consensus document has been recently developed to provide upgraded criteria (“the Padua Criteria”) for the diagnosis of the whole spectrum of ACM phenotypes, particularly left-dominant forms, highlighting the use of cardiac magnetic resonance. This review aims to offer an overview of the current knowledge on the genetic basis, the phenotypic expressions, and the diagnosis of left-sided variants, both biventricular and left-dominant, of ACM.

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