Heart failure and sudden cardiac death in heritable thoracic aortic disease caused by pathogenic variants in the SMAD3 gene

Background: Predominant cardiovascular manifestations in the spectrum of Heritable Thoracic Aortic Disease include by default aortic root aneurysms- and dissections, which may be associated with aortic valve disease. Mitral- and tricuspid valve prolapse are other commonly recognized features. Myocardial disease, characterized by heart failure and/or malignant arrhythmias has been reported in humans and in animal models harboring pathogenic variants in the Fibrillin1 gene. Methods: Description of clinical history of three cases from one family in Ghent (Belgium) and one family in St. Louis (US). Results: We report on three cases from two families presenting end-stage heart failure (in two) and lethal arrhythmias associated with moderate left ventricular dilatation (in one). All three cases harbor a pathogenic variant in the SMAD3 gene, known to cause aneurysm osteoarthritis syndrome, Loeys-Dietz syndrome type 3 or isolated Heritable Thoracic Aortic Disease. Conclusions: These unusual presentations warrant awareness for myocardial disease in patients harboring pathogenic variants in genes causing Heritable Thoracic Aortic Disease and indicate the need for prospective studies in larger cohorts

Cardiac troponin I as compared to troponin T for the detection of myocardial damage in horses

Background: Different cardiac troponin I (cTnI) assays give different results. Only 1 manufacturer has marketed troponin T (cTnT) assays. Therefore, cTnT often is preferred for detection of myocardial infarction in human patients. Studies of cTnT in horses are limited. Objectives: To compare a cTnI and a high-sensitive cTnT assay (hs-cTnT) in horses. Animals: Cardiac troponin I and cTnT were determined in 35 healthy horses (group 1), 23 horses suspected to have primary myocardial damage (group 2a), and 41 horses with secondary myocardial damage caused by structural heart disease (group 2b). Methods: All cTnI samples were analyzed at laboratory A (limit of detection [LOD]: 0.03 ng/mL), whereas cTnT samples were analyzed at 2 laboratories with the same hs-cTnT assay (laboratory B, LOD: 10.0 pg/mL; laboratory C, LOD: 4.0 pg/mL). Results: The median cTnI concentration in group 2a (0.90 ng/mL; range, 0.03–58.27 ng/mL) was significantly higher (P < .001) than in group 1 (0.03 ng/mL; range, 0.03–0.09 ng/mL) or group 2b (0.05 ng/mL; range, 0.03–30.92 ng/mL), and the optimal cut-off for detection of primary myocardial damage was 0.095 ng/mL (sensitivity: 90.5%, specificity: 100%). Using an LOD of 10.0 pg/mL for all cTnT samples, a cut-off value of 10.5 pg/mL was found, but sensitivity was low (42.9%). When only samples analyzed at laboratory C (n = 58) were included, a cut-off of 6.6 pg/mL was found (sensitivity: 81%, specificity: 100%). Conclusions and Clinical Importance: Despite large quantitative differences, cTnI and cTnT are both useful for detection of myocardial damage in horses

Cardiac Magnetic Resonance Imaging-Based Screening for Cardiac Sarcoidosis in Patients With Atrioventricular Block Requiring Temporary Pacing

Background Some myocardial diseases, such as cardiac sarcoidosis, predispose to complete atrioventricular block. The European Society of Cardiology Guidelines on cardiac pacing in 2021 recommend myocardial disease screening in patients with conduction disorder requiring pacemaker with multimodality imaging, including cardiac magnetic resonance (CMR) imaging. The ability of CMR imaging to detect myocardial disease in patients with a temporary pacing wire is not well documented. Methods and Results Our myocardial disease screening protocol is based on using an active fixation pacing lead connected to a reusable extracorporeal pacing generator (temporary permanent pacemaker) as a bridge to a permanent pacemaker. From 2011 to 2019, we identified 17 patients from our CMR database who underwent CMR imaging with a temporary permanent pacemaker for atrioventricular block. We analyzed their clinical presentations, CMR data, and pacemaker therapy. All CMRs were performed without adverse events. Pacing leads induced minor artifacts to the septal myocardial segments. The extent of late gadolinium enhancement in CMR imaging was used to screen patients for the presence of myocardial disease. Patients with evidence of late gadolinium enhancement underwent endomyocardial biopsy. If considered clinically indicated, also 18-F-fluorodeoxyglucose positron emission tomography and extracardiac tissue biopsy were performed if sarcoidosis was suspected. Eventually, 8 of 17 patients (47.1%) were diagnosed with histologically confirmed granulomatous inflammatory cardiac disease. Importantly, only 1 had a previously diagnosed extracardiac sarcoidosis at the time of presentation with high-degree atrioventricular block. Conclusions CMR imaging with temporary permanent pacemaker protocol is an effective and safe early screening tool for myocardial disease in patients presenting with atrioventricular block requiring immediate, continuous pacing for bradycardia.Peer reviewe

Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

Subclinical myocardial disease by cardiac magnetic resonance imaging and spectroscopy in healthy HIV/Hepatitis C virus-coinfected persons.

Objective The contribution of hepatitis C virus (HCV) infection to the risk of heart failure in human immunodeficiency virus (HIV)-coinfected persons is unknown. The objective was to characterize cardiac function and morphology in HIV-treated coinfected persons. Methods In a cross-sectional study, HIV-infected patients virologically suppressed on antiretroviral therapy without known cardiovascular disease or diabetes mellitus underwent cardiac magnetic resonance imaging and spectroscopy for measures of cardiac function, myocardial fibrosis, and steatosis. Results The study included 18 male patients with a median age of 44 years. Of these, 10 had untreated HCV coinfection and eight had HIV monoinfection. Global systolic and diastolic function in the cohort were normal, and median myocardial fat content was 0.48% (interquartile range 0.35-1.54). Left ventricular (LV) mass index and LV mass/volume ratio were significantly greater in the HIV/HCV-coinfected group compared with the HIV-monoinfected group. In the HIV-monoinfected group, there was more myocardial fibrosis as measured by extracellular volume fraction. Conclusions There were differences between HIV/HCV-coinfected and HIV-monoinfected patients in cardiac structure and morphology. Larger studies are needed to examine whether HIV and HCV independently contribute to mechanisms of heart failure

Cardiomyopathies in Animals

A wide variety of animal models in cardiomyopathy have been established for the discovery of pathophysiological mechanisms, diagnosis, and treatment of human myocardial disease. Experimentally, several species including rodents, rabbit, canine, pig, and sheep have been involved in the fundamental research in medical field. However, knowledge about naturally occurring myocardial disease in animals is limited in the veterinary medicine. Among small and large animals that develop myocardial disease, to the best of authors’ knowledge, naturally occurring cardiomyopathy in canine and feline is commonly encountered in veterinary clinical setting. Their pathophysiology is not fully described; specific pathophysiology is documented in both species, which resembles those of humans. These conditions are hypertrophic cardiomyopathy (HCM) in feline and dilated cardiomyopathy (DCM) in canine. Each has distinct etiology and pathophysiology. In order to translate new findings from naturally occurring cardiomyopathies in small and large animals into medical applications, knowledge gained through animals with cardiomyopathies becomes a necessary approach. The purpose of this chapter is to introduce the overview of findings on small and large animals with naturally occurring cardiomyopathies already investigated

International criteria for electrocardiographic interpretation in athletes: Consensus statement.

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly, advanced by a growing body of scientific data and investigations that both examine proposed criteria sets and establish new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington (USA), to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD

A case of non-compaction cardiomyopathy

The aim of this case report was to present a rare myocardial disease, the so-called isolated non-compaction cardiomyopathy (NCCM). This disorder, a primary genetic cardiomyopathy, attracts increasing attention. A woman with a sudden onset of shortness of breath and isolated NCCM is described. Criteria for diagnosis as well as echocardiographic findings and magnetic resonance imaging of the heart are presented. Although rare, a new option of myocardial disease with various modes of clinical presentation but, most commonly, with acute or chronic heart failure should be taken into consideration. Multiple imaging modalities are available and should be used for proper diagnosis.Scripta Scientifica Medica 2013; 45(3): 86-89