BackgroundLong QT syndrome type 3 (LQT3) is a lethal disease caused by gain-of-function mutations in the SCN5A gene, coding for the alpha-subunit of the sodium channel NaV1.5. Mexiletine is used to block late sodium current and to shorten QT interval in LQT3 patients.ObjectivesThe aim of this study was to determine whether mexiletine prevents arrhythmic events (arrhythmic syncope, aborted cardiac arrest, or sudden cardiac death) in LQT3 patients.MethodsThe endpoint of this retrospective cohort study, which studied consecutive LQT3 patients who were referred to our center and treated with mexiletine, was to evaluate the antiarrhythmic efficacy of mexiletine by comparing the number of arrhythmic events per patient and the annual rate of arrhythmic events during observation periods of equal duration before and after the beginning of therapy with mexiletine.ResultsThe study population comprised 34 LQT3 patients, 19 (56%) of whom were male. The median age at beginning of treatment with mexiletine was 22 years, and median QTc interval before therapy 509 ms. The median duration of oral mexiletine therapy was 36 months, at an average daily dose of 8 ± 0.5 mg/kg. Mexiletine significantly shortened QTc (by 63 ± 6 ms; p < 0.0001) and reduced the percentage of patients with arrhythmic events (from 22% to 3%; p = 0.031), the mean number of arrhythmic events per patient (from 0.43 ± 0.17 to 0.03 ± 0.03; p = 0.027), and the annual rate of arrhythmic events (from 10.3% to 0.7%; p = 0.0097).ConclusionsBesides shortening QTc interval, mexiletine caused a major reduction of life-threatening arrhythmic events in LQT3 patients, thus representing an efficacious therapeutic strategy.
The high risk of life-threatening arrhythmias in patients with ARVC spans from adolescence to advanced age, reaching its peak between ages 21 and 40 years. Atrial fibrillation, syncope, participation in strenuous exercise after the diagnosis of ARVC, hemodynamically tolerated sustained monomorphic ventricular tachycardia, and male sex predicted lethal arrhythmias at follow-up. The lack of efficacy of antiarrhythmic therapy and the life-saving role of the implantable cardioverter-defibrillator highlight the importance of risk stratification for patient management.
Background: Despite the ongoing global pandemic, the impact of COVID-19 on cardiac structure and function is still not completely understood. Myocarditis is a rare but potentially serious complication of other viral infections with variable recovery, and is, in some cases, associated with long-term cardiac remodeling and functional impairment.Aim: To assess myocardial injury in patients who recently recovered from an acute SARS-CoV-2 infection with advanced cardiac magnetic resonance imaging (CMR) and endomyocardial biopsy (EMB).Methods: In total, 32 patients with persistent cardiac symptoms after a COVID-19 infection, 22 patients with acute classic myocarditis not related to COVID-19, and 16 healthy volunteers were included in this study and underwent a comprehensive baseline CMR scan. Of these, 10 patients post COVID-19 and 13 with non-COVID-19 myocarditis underwent a follow-up scan. In 10 of the post-COVID-19 and 15 of the non-COVID-19 patients with myocarditis endomyocardial biopsy (EMB) with histological, immunohistological, and molecular analysis was performed.Results: In total, 10 (31%) patients with COVID-19 showed evidence of myocardial injury, eight (25%) presented with myocardial oedema, eight (25%) exhibited global or regional systolic left ventricular (LV) dysfunction, and nine (28%) exhibited impaired right ventricular (RV) function. However, only three (9%) of COVID-19 patients fulfilled updated CMR–Lake Louise criteria (LLC) for acute myocarditis. Regarding EMB, none of the COVID-19 patients but 87% of the non-COVID-19 patients with myocarditis presented histological findings in keeping with acute or chronic inflammation. COVID-19 patients with severe disease on the WHO scale presented with reduced biventricular longitudinal function, increased RV mass, and longer native T1 times compared with those with only mild or moderate disease.Conclusions: In our cohort, CMR and EMB findings revealed that SARS-CoV-2 infection was associated with relatively mild but variable cardiac involvement. More symptomatic COVID-19 patients and those with higher clinical care demands were more likely to exhibit chronic inflammation and impaired cardiac function compared to patients with milder forms of the disease.
Due to an increasingly aging population, Alzheimer disease (AD) represents a crucial issue for the healthcare system because of its widespread prevalence and the burden of its care needs. Several hypotheses on AD pathogenesis have been proposed and current therapeutical strategies have shown limited effectiveness. In the last decade, more evidence has supported a role for neuroinflammation and immune system dysregulation in AD. It remains unclear whether astrocytes, microglia and immune cells influence disease onset, progression or both. Amyloid-β peptides that aggregate extracellularly in the typical neuritic plaques generate a constant inflammatory environment. This causes a prolonged activation of microglial and astroglial cells that potentiate neuronal damage and provoke the alteration of the blood brain barrier (BBB), damaging the permeability of blood vessels. Recent data support the role of the BBB as a link between neuroinflammation, the immune system and AD. Hence, a thorough investigation of the neuroinflammatory and immune system pathways that impact neurodegeneration and novel exciting findings such as microglia-derived microvesicles, inflammasomes and signalosomes will ultimately enhance our understanding of the pathological process. Eventually, we should proceed with caution in defining a causal or consequential role of neuroinflammation in AD, but rather focus on identifying its exact pathological contribution.
Pressure–volume (PV) analysis is the most comprehensive way to describe cardiac function, giving insights into cardiac mechanics and energetics. However, PV analysis still remains a highly invasive and time-consuming method, preventing it from integration into clinical practice. Most of the echocardiographic parameters currently used in the clinical routine to characterize left ventricular (LV) systolic function, such as LV ejection fraction and LV global longitudinal strain, do not take the pressure developed within the LV into account and therefore fall too short in describing LV function as a hydraulic pump. Recently, LV pressure-strain analysis has been introduced as a new technique to assess myocardial work in a non-invasive fashion. This new method showed new insights in comparison to invasive measurements and was validated in different cardiac pathologies, e.g., for the detection of coronary artery disease, cardiac resynchronization therapy (CRT)-response prediction, and different forms of heart failure. Non-invasively assessed myocardial work may play a major role in guiding therapies and estimating prognosis. However, its incremental prognostic validity in comparison to common echocardiographic parameters remains unclear. This review aims to provide an overview of pressure-strain analysis, including its current application in the clinical arena, as well as potential fields of exploitation.
Heart failure (HF) patients represent one of the most prevalent as well as one of the most fragile population encountered in the cardiology and internal medicine departments nowadays. Estimated to account for around 26 million people worldwide, diagnosed patients present a poor prognosis and quality of life with a clinical history accompanied by repeated hospital admissions caused by an exacerbation of their chronic condition. The frequent hospitalizations and the extended hospital stays mean an extremely high economic burden for healthcare institutions. Meanwhile, the number of chronically diseased and elderly patients is continuously rising, and a lack of specialized physicians is evident. To cope with this health emergency, more efficient strategies for patient management, more accurate diagnostic tools, and more efficient preventive plans are needed. In recent years, telemonitoring has been introduced as the potential answer to solve such needs. Different methodologies and devices have been progressively investigated for effective home monitoring of cardiologic patients. Invasive hemodynamic devices, such as CardioMEMS™, have been demonstrated to be reducing hospitalizations and mortality, but their use is however restricted to limited cases. The role of external non-invasive devices for remote patient monitoring, instead, is yet to be clarified. In this review, we summarized the most relevant studies and devices that, by utilizing non-invasive telemonitoring, demonstrated whether beneficial effects in the management of HF patients were effective.
<b><i>Background:</i></b> Patients affected by chronic kidney disease are at a risk of cardiovascular morbidity and mortality. Body fluids unbalance is one of the main characteristics of this condition, as fluid overload is highly prevalent in patients affected by the cardiorenal syndrome. <b><i>Summary:</i></b> We describe the state of the art and new insights into body volume evaluation. The mechanisms behind fluid balance are often complex, mainly because of the interplay of multiple regulatory systems. Consequently, its management may be challenging in clinical practice and even more so out-of-hospital. Availability of novel technologies offer new opportunities to improve the quality of care and patients’ outcome. Development and validation of new technologies could provide new tools to reduce costs for the healthcare system, promote personalized medicine, and boost home care. Due to the current COVID-19 pandemic, a proper monitoring of chronic patients suffering from fluid unbalances is extremely relevant. <b><i>Key Message:</i></b> We discuss the main mechanisms responsible for fluid overload in different clinical contexts, including hemodialysis, peritoneal dialysis, and heart failure, emphasizing the potential impact provided by the implementation of the new technologies.
Cardiovascular magnetic resonance feature tracking (CMR-FT) is a novel technique for non-invasive assessment of myocardial motion and deformation. Although CMR-FT is standardized in humans, literature on comparative analysis from animal models is scarce. In this study, we measured the reproducibility of global strain under various inotropic states and the sample size needed to test its relative changes in pigs. Ten anesthetized healthy Landrace pigs were investigated. After baseline (BL), two further steps were performed: (I) dobutamine-induced hyper-contractility (Dob) and (II) verapamil-induced hypocontractility (Ver). Global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) were assessed. This study shows a good to excellent inter- and intra-observer reproducibility of CMR-FT in pigs under various inotropic states. The highest inter-observer reproducibility was observed for GLS at both BL (ICC 0.88) and Ver (ICC 0.79). According to the sample size calculation for GLS, a small number of animals could be used for future trials.
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