Inherited heart disease represent a very heterogenous group of cardiac disorders, characterized by inherited, acquired, and often rare disorders affecting the heart muscle (cardiomyopathies) or the ...cardiac electrical system (ion channel disease). They are often familial diseases, and are among the leading cause of juvenile sudden death and heart failure. The aim of this paper is to give a perspective on how to run a clinical service during an epidemic or pandemic emergency and to describe the potential COVID-19 associated risks for patients affected by inherited heart diseases.
In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of ...the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance.
Atherosclerosis represents the most common pathological substrate of coronary heart disease (CHD), and the characterization of the disease as a chronic low-grade inflammatory condition is now largely ...accepted. A number of mediators of inflammation have been widely studied, both as surrogate biomarkers and as causal agents, in the pathophysiological network of atherogenesis and plaque vulnerability. The epidemiological observation that biomarkers of inflammation are associated with clinical cardiovascular risk supports the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk on the background of traditional medical therapy. A large number of randomized controlled trials have shown that drugs commonly used in cardiovascular disease (CVD), such as statins, may be effective in the primary and secondary prevention of cardiovascular events through an anti-inflammatory effect. Moreover, several anti-inflammatory drugs are being tested for their potential to reduce residual cardiovascular risk on the background of validated medical therapy for atherosclerotic disease. In this paper, we review relevant evidence with regard to the relationship between inflammation and CVD, from pathogenesis to therapeutic strategies.
Coronavirus disease 2019 (COVID-19) has substantially challenged healthcare systems worldwide. By investigating population characteristics and prescribing profiles, it is possible to generate ...hypotheses about the associations between specific drug-utilisation profiles and susceptibility to COVID-19 infection. A retrospective drug-utilisation study was carried out using routinely collected information from a healthcare database in Campania (Southern Italy). We aimed to discover the prevalence of drug utilisation (monotherapy and polytherapy) in COVID-19 versus non-COVID-19 patients in Campania (~ 6 million inhabitants). The study cohort comprised 1532 individuals who tested positive for COVID-19. Drugs were grouped according to the Anatomical Therapeutic Chemical (ATC) classification system. We noted higher prevalence rates of the use of drugs in the ATC categories C01, B01 and M04, which was probably linked to related comorbidities (i.e., cardiovascular and metabolic). Nevertheless, the prevalence of the use of drugs acting on the renin-angiotensin system, such as antihypertensive drugs, was not higher in COVID-19 patients than in non-COVID-19 patients after adjustments for age and sex. These results highlight the need for further case-control studies to define the effects of medications and comorbidities on susceptibility to and associated mortality from COVID-19.
Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms ...that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions. Moreover, VWF and ADAMTS13 have been recently proposed as prognostic biomarkers in cardiovascular, metabolic, and inflammatory diseases, such as diabetes, stroke, myocardial infarction, and sepsis. All these features make VWF an attractive therapeutic target in thromboinflammation. Several lines of research have recently investigated “tailor-made” inhibitors of VWF. Results from animal models and clinical studies support the potent anti-inflammatory and antithrombotic effect of VWF antagonism, providing reassuring data on its safety profile. This review describes the role of VWF in vascular inflammation “from bench to bedside” and provides an updated overview of the drugs that can directly interfere with the VWF/ADAMTS13 axis.
Aims To perform a systematic literature review and meta-analysis of clinical risk factors for sudden cardiac death (SCD) in childhood hypertrophic cardiomyopathy. Methods Medline and PubMed databases ...were searched for original articles published in English from 1963 through to December 2015 that included patients under 18 years of age with a primary or secondary end-point of either SCD or SCD-equivalent events (aborted cardiac arrest or appropriate implantable cardioverter-defibrillator discharge) or cardiovascular death (CVD). Results Twenty-five studies (3394 patients) met the inclusion criteria. We identified four conventional major risk factors that were evaluated in at least four studies and that we found to be statistically associated with an increased risk of death in at least two studies: previous adverse cardiac event (pooled hazard ratio HR 5.4, 95% confidence interval CI 3.67-7.95, p < 0.001); non-sustained ventricular tachycardia (pooled HR 2.13, 95% CI 1.21-3.74, p = 0.009); unexplained syncope (pooled HR 1.89, 95% CI 0.69-5.16, p = 0.22); and extreme left ventricular hypertrophy (pooled HR 1.80, 95% CI 0.75-4.32, p = 0.19). Left atrial diameter did not meet the major risk factor criteria; however, this is likely to be an additional significant risk factor. 'Minor' risk factors included a family history of SCD, gender, age, symptoms, electrocardiogram changes, abnormal blood pressure response to exercise and left ventricular outflow tract obstruction. Conclusions A lack of well-designed, large, population-based studies in childhood hypertrophic cardiomyopathy means that the evidence base for individual risk factors is not robust. We have identified four clinical parameters that are likely to be associated with increased risk of SCD, SCD-equivalent events or CVD. Multi-centre prospective studies are needed in order to further determine the relevance of these factors in predicting SCD in childhood hypertrophic cardiomyopathy and to identify novel risk markers. Condensed abstract A systematic review and meta-analysis of clinical risk factors predicting sudden cardiac death in childhood hypertrophic cardiomyopathy was performed, identifying four 'major' factors: previous adverse cardiac event; non-sustained ventricular tachycardia; syncope; and extreme left ventricular hypertrophy. Well-designed multi-centre studies are required in the future in order to confirm these findings.
Background:Heart failure (HF) progression and its complications represent major emergent concerns in hypertrophic cardiomyopathy (HCM). We investigated the possible adjunctive role of cardiopulmonary ...exercise testing (CPET) in predicting HF-related events. An exercise-derived risk model, theHYPertrophicExercise-derivedRiskHF(HYPERHF), has been developed.Methods and Results:A multicenter cohort of 620 consecutive HCM outpatients was recruited and followed (2007 to 2015). The endpoint was death from HF, cardiac transplantation, NYHA III–IV class progression, severe functional deterioration leading to hospitalization for septal reduction, and hospitalization for HF worsening. During a median follow-up of 3.8 years (25–75th centile: 2.3–5.3 years), 84 patients reached the endpoint. Peak circulatory power (peak oxygen consumption * peak systolic blood pressure), ventilatory efficiency and left atrial diameter were independently associated with the endpoint and, accordingly, integrated into the HYPERHFmodel (C index: 0.849; best cutoff value equal to 15%).Conclusions:CPET is useful in the evaluation of HCM patients. In this context, the HYPERHFscore might allow early identification of those patients at high risk of HF progression and its complications. (Circ J 2016; 80: 2204–2211)
Abstract Paediatric heart failure (PHF) represents an important cause of morbidity and mortality in childhood. Currently, there are well-established guidelines for the management of heart failure in ...the adult population, but an equivalent consensus in children is lacking. In the clinical setting, ensuring an accurate diagnosis and defining aetiology is essential to optimal treatment. Diuretics and angiotensin-converting enzyme inhibition are the first-line therapies, whereas beta-blockers and device for electric therapy are less used in children than in adults. In the end-stage disease, heart transplantation is the best choice of treatment, while a left ventricular assist device can be used as a bridge to transplantation (due to the difficulties in finding organ donors), recovery (in the case of myocarditis), or destination therapy (for patients with systemic disease).
Cardiomyopathies (CMPs) represent a diverse group of heart muscle diseases, grouped into specific morphological and functional phenotypes. CMPs are associated with mutations in sarcomeric and ...non-sarcomeric genes, with several suspected epigenetic and environmental mechanisms involved in determining penetrance and expressivity. The understanding of the underlying molecular mechanisms of myocardial diseases is fundamental to achieving a proper management and treatment of these disorders. Among these, inflammation seems to play an important role in the pathogenesis of CMPs. The aim of the present study is to review the current knowledge on the role of inflammation and the immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a crucial role in lipid metabolism, particularly due to its function in low‐density lipoprotein receptor degradation. Gain‐of‐function ...genetic mutations of PCSK9 result in autosomal dominant familial hypercholesterolemia, characterized by high levels of low‐density lipoprotein cholesterol (LDL‐C) and clinical signs of early atherosclerosis. In recent years, PCSK9 has become an important therapeutic target for cholesterol‐lowering therapy. Particularly, its inhibition with monoclonal antibodies has shown excellent efficacy in decreasing LDL‐C and reducing cardiovascular events. However, PCSK9, first identified in the brain, seems to be a ubiquitous protein with different tissue‐specific functions also independent of cholesterol metabolism. Accordingly, it appears to be involved in the immune response, haemostasis, glucose metabolism, neuronal survival, and several other biological functions. This review provides a comprehensive overview of the genetics, biochemical structure, expression, and function of PCSK9 and discusses the potential implications of its long‐term pharmacological inhibition.
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