Search Results (89)

Background: Pediatric heart failure (PHF) is a heterogeneous syndrome with high morbidity, but existing classification systems inadequately capture its developmental and pathophysiological complexity due to reliance on adult-centric parameters. Using machine learning, we aimed to identify clinically distinct PHF phenotypes with unique outcomes and therapeutic implications. Methods: In this multicenter retrospective study, we analyzed 2903 consecutive PHF patients (≤18 years) from 30 Chinese tertiary centers from 20 provinces (2013–2022). Unsupervised machine learning (k-means clustering with PCA) evaluated 99 clinical, biomarker, and echocardiographic variables to derive phenotypes, which were compared for mortality, hospitalization, and treatment responses. Results: Three phenotypically distinct clusters emerged. Cluster 1 (Chronic Hypertensive and Cardiorenal Profile, 30.1%) predominantly affected older children (78%) with hypertension (54.4%), renal dysfunction (creatinine 45.8 μmol/L), and ventricular tachycardia (53.8%). This cluster showed the lowest in-hospital mortality (2.5%) but frequent 7–14 day hospitalizations (35.8%) and the highest beta-blocker use (54.5%). Cluster 2 (Preterm and CHD-Associated HF, 43.4%) comprised preterm infants (71.4%) with congenital heart disease (72.2%) and preserved LVEF (67%), demonstrating the highest mortality (5.1%) and prolonged stays (>30 days: 10.6%) with predominant diuretic (40.6%) and antibiotic use (54.3%). Cluster 3 (Fulminant Myocarditis Profile, 26.5%) exhibited cardiogenic shock with severely reduced LVEF (33%) and elevated BNP (3234 pg/mL), showing bimodal outcomes (4.8% LOS < 3 days vs. 32.2% LOS 15–30 days) and the highest IVIG utilization (46.5%) with intermediate mortality (3.8%). The majority of between-group differences were statistically significant (p < 0.001). Conclusions: Machine learning identified three PHF phenotypes with distinct in-hospital risk profiles and therapeutic implications, challenging current classification systems. These findings highlight the potential for phenotype-specific management strategies and provide a rationale for future research into arrhythmia prevention in hypertensive profiles and early immunomodulation in fulminant myocarditis, while highlighting the need for specialized care pathways for preterm/CHD patients. Prospective validation is warranted to translate this framework into clinical practice. Full article

Despite substantial progress in medical care, acute myocarditis remains a life-threatening disorder with a sudden onset, often unexpectedly complicating a simple and common upper respiratory tract infection. In most cases, myocarditis is triggered by viral infections (over 80%), with an estimated incidence of 10–106 per 100,000 annually. The clinical course may worsen in cases of mixed etiology, where a primary viral infection is complicated by secondary bacterial pathogens, leading to prolonged inflammation and an increased risk of progression to chronic active myocarditis or dilated cardiomyopathy. We present a case report illustrating the clinical problem of acute myocarditis progression into a chronic active form. A central element of host defense is the inflammasome—an intracellular complex that activates pyroptosis and cytokine release (IL-1β, IL-18). While these processes help combat pathogens, their persistent activation may sustain inflammation and trigger heart failure and cardiac fibrosis, eventually leading to dilated cardiomyopathy. In this review, we summarize the current understanding of inflammasome pathways and their dual clinical role in myocarditis: they are essential for controlling acute infection but may become harmful when overactivated, contributing to chronic myocardial injury. Additionally, we discuss both novel and established therapeutic strategies targeting inflammatory and anti-fibrotic mechanisms, including IL-1 receptor blockers (anakinra, canakinumab), NOD-like receptor protein 3 (NLRP3) inhibitors (colchicine, MCC950, dapansutrile, INF200), NF-κB inhibitors, and angiotensin receptor-neprilysin inhibitors (ARNI), as well as microRNAs. Our aim is to emphasize the clinical importance of early identification of patients at risk of transitioning from acute to chronic inflammation, elucidate the role of inflammasomes, and present emerging therapies that may improve outcomes by balancing effective pathogen clearance with limitation of chronic cardiac damage. Full article

Coxsackievirus B3 (CVB3) is a primary causative agent of viral myocarditis (VMC), which can lead to both acute and chronic cardiac inflammation accompanied by progressive heart failure and arrhythmias. Although CVB3 has been implicated in various forms of programmed cell death, whether it triggers necroptosis and the underlying mechanisms remains unclear. This study aimed to investigate the role and mechanism of CVB3-induced necroptosis and its effect on viral replication. Using both in vitro and in vivo models, we demonstrated that CVB3 infection significantly upregulates the expression of key necroptotic markers RIP1 and RIP3 in HeLa cells and mouse myocardial tissues. This upregulation was accompanied by elevated intracellular reactive oxygen species (ROS) levels and suppression of the Nrf2/HO-1 antioxidant pathway. Intervention with the necroptosis inhibitor Necrostatin-1 (Nec-1) or the ROS scavenger N-acetylcysteine (NAC) markedly attenuated cell death, suppressed viral replication, and ameliorated myocardial injury and inflammatory responses in infected mice. Mechanistically, CVB3 inhibits the Nrf2/HO-1 pathway, thereby inducing substantial ROS accumulation that promotes necroptosis. This effect can be reversed by NAC treatment. Our study reveals a novel mechanism through which CVB3 induces ROS-dependent necroptosis via the suppression of the Nrf2/HO-1 pathway, providing new insights into the pathogenesis of viral myocarditis and suggesting potential therapeutic strategies. Full article

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant racial and ethnic disparities in prevalence, disease severity, and outcomes. Cardiovascular complications, including pericarditis, myocarditis, valvular disease, and conduction abnormalities, contribute to increased morbidity and mortality in SLE patients. This study examines racial and ethnic disparities in cardiovascular outcomes among hospitalized SLE patients in the United States. Methods: This retrospective study utilized the National Inpatient Sample (NIS) database from 2016 to 2021 to analyze hospitalizations of adult patients (≥18 years) with a primary or secondary diagnosis of SLE. Patients were stratified into racial/ethnic groups: White, Black, Hispanic, Asian, Native American, and Other. Primary outcomes include major adverse cardiovascular events (MACEs), which are a composite of in-hospital mortality, myocardial infarction (MI), sudden cardiac death, and other SLE-related outcomes including cardiac, pulmonary, and renal involvement. Statistical analyses included multivariable logistic regression models adjusted for demographic, socioeconomic, and hospital-related factors to assess racial disparities. Results: The study included 514,750 White, 321,395 Black, and 146,600 Hispanic patients, with smaller proportions of Asian, Native American, and Other racial groups. Black patients had significantly higher odds of in-hospital mortality (OR = 1.17, 95% CI = 1.08–1.26, p < 0.001) and sudden cardiac death (OR = 1.64, 95% CI = 1.46–1.85, p < 0.001) compared to White patients. Asian patients also exhibited increased mortality risk (OR = 1.37, 95% CI = 1.14–1.63, p = 0.001) as compared to Whites. Conversely, Black (OR = 0.90, 95% CI = 0.85–0.96, p = 0.01) and Hispanic (OR = 0.87, 95% CI = 0.80–0.96, p = 0.03) patients had lower odds of MI. Racial disparities in access to care, socioeconomic status, and comorbidity burden may contribute to these differences. Conclusion: Significant racial and ethnic disparities exist in cardiovascular outcomes among hospitalized SLE patients. Black and Asian individuals face higher in-hospital all-causes mortality and sudden cardiac death risks, while Black and Hispanic patients exhibit lower MI rates. Addressing social determinants of health, improving access to specialized care, and implementing targeted interventions may reduce disparities and improve outcomes in minority populations with SLE. Full article

Background: This study investigates the potential mechanisms behind changes in cardiac structure and function in long COVID patients. Methods: This study involved 176 consecutive outpatients in follow-up care (average age 55.9 years; 58.5% male) who experienced symptoms for over 12 weeks (average 6.2 ± 2.7 months), following coronavirus infection (COVID-19). Results: The patients with long COVID and cardiovascular manifestations were significantly more hospitalized (88.5% vs. 75.9%) and had longer hospital stays. Significant echocardiography changes were observed in the left ventricular ejection fraction (LVEF) (59.6 ± 5.4% vs. 62.5 ± 3.8%); longitudinal strain (LS) in the sub-endocardium and intra-myocardium layers (−20.9 vs. −22.0% and −18.6 vs. −19.5%); circumferential strain (CS) in the sub-epicardium layers (−9.6 vs. −10.5%); and CS post-systolic shortening (CS PSS) (0.138 vs. 0.088 s). Additionally, pathological cardiac magnetic resonance (CMR) findings were seen in 58.2% of the group of patients with long COVID and cardiovascular manifestation; 43.3% exhibited positive late gadolinium enhancement (LGE), 21.0% had elevated native T1 mapping, and 22.4% had elevated native T2 mapping. Conclusions: Most patients with long COVID showed structural and functional changes in their cardiovascular systems, primarily caused by prolonged inflammation. Using multimodality imaging is important for uncovering the mechanisms to predict chronic myocarditis, early-stage heart failure, and pre-ischemic states, which can lead to serious complications. Recognizing the specific cardiovascular phenotypes associated with long COVID is essential in order to provide timely and appropriate treatment. Full article

Background: Idiopathic inflammatory myopathies (IIMs), also known as myositis, are systemic autoimmune diseases characterized by chronic inflammation affecting the skin, muscles, and internal organs. Besides traditional risk factors and immune-mediated myocarditis, continuous activity of the immune system increases cardiovascular disease (CVD) risk, meaning that cardiovascular events are the leading causes of mortality in IIM patients. Statins are the most widely used lipid-lowering therapies, which reduce cardiovascular risk, but the fear of adverse muscular events inhibits the frequency of use. Methods: Our aim was to assess the CVD risk in a myositis cohort using the SCORE2 prediction system, carotid artery Doppler ultrasound measurement, and biomarkers; recommend individual lipid-lowering treatment; and follow the efficacy and adverse events of therapy in a 6-month treatment period. Results: The study population (80 IIM patients) was a middle-aged, female-dominant myositis cohort with an average disease duration of 9 years and low median global disease activity. Based on the SCORE2 evaluation, 78.8% of patients had medium/high CVD risk, while 73.13% had asymptomatic carotid plaque. After 6 months of adequate lipid-lowering therapy, 37.5% of patients reached a lower CVD risk category, the biomarker levels of atherosclerosis significantly decreased, and no progression in carotid plaques was detected. None of the patients reported an adverse muscular event or IIM relapse. Conclusions: Our findings proved that the CVD risk of patients with myositis is high, but carefully applied lipid-lowering treatment is the key to effective risk reduction. Risk stratification and the recommendation of preventive treatment are the responsibility of the treating physician. Full article

Trypanosoma cruzi, the causal agent of Chagas disease, exhibits great genetic diversity, which has been related to its biological properties. However, these are poorly known in strains from the endemic area of Hidalgo. To assess the parasite’s virulence, we evaluated parasitemia, mortality, and tropism in thirteen organs of CD1 mice during the acute phase of infection. For genotyping, we amplified the mini-exon gene from T. cruzi DNA using PCR. All five isolates were identified as belonging to DTU TcI. The peak of parasitemia occurred between 25 and 29 days post-infection. The Tultitlán and Olma isolates did not cause any mouse deaths, whereas Ixcatépec produced 100% mortality. Mice infected with the Barrio Hondo isolate exhibited the highest parasitemia, while those infected with Cuatecomaco had the lowest. The five isolates generated varying degrees of infection and chronic inflammation; only two isolates triggered acute pancreatitis and myocarditis. No amastigote nests were found in the hearts of mice infected with the Ixcatépec isolate. Our findings suggest that the damage caused by T. cruzi strains from Hidalgo may extend beyond cardiac lesions in the acute phase of Chagas disease regardless of their classification as TcI and variability in parasitemia levels. Full article

The mRNA- and DNA-based “genetic” COVID-19 vaccines can induce a broad range of adverse events (AEs), with statistics showing significant variation depending on the timing and data analysis methods used. Focusing only on lipid nanoparticle-enclosed mRNA (mRNA-LNP) vaccines, this review traces the evolution of statistical conclusions on the prevalence of AEs and incidents associated with these vaccines, from initial underestimation of atypical, severe toxicities to recent claims suggesting the possible contribution of COVID-19 vaccinations to the excess deaths observed in many countries over the past few years. Among hundreds of different AEs listed in Pfizer’s pharmacovigilance survey, the present analysis categorizes the main symptoms according to organ systems, with nearly all of them being affected. Using data from the US Vaccine Adverse Event Reporting System and a global vaccination dataset, a comparison of the prevalence and incidence rates of AEs induced by genetic versus flu vaccines revealed an average 26-fold increase in AEs with the use of genetic vaccines. The difference is especially pronounced in the case of severe ‘Brighton-listed’ AEs, which are also observed in COVID-19 and post-COVID conditions. Among these, the increases in incidence rates relative to flu vaccines, given as x-fold rises, were 1152x, 455x, 226x, 218x, 162x, 152x, and 131x for myocarditis, thrombosis, death, myocardial infarction, tachycardia, dyspnea, and hypertension, respectively. The review delineates the concept that genetic vaccines can be regarded as prophylactic immuno-gene therapies and that the observed chronic disabling AEs might be categorized as iatrogenic orphan diseases. It also examines the unique vaccine characteristics that could be causally related to abnormal immune responses which potentially lead to adverse events and complications. These new insights may contribute to improving the safety of this platform technology and assessing the risk/benefit balance of various products. Full article

Canine monocytic ehrlichiosis (CME) is a globally prevalent disease transmitted by the tick Rhipicephalus sanguineus and caused by the Gram-negative bacterium Ehrlichia spp. Following an incubation period, the infection is categorized based on the progression of the disease into acute, subclinical, and chronic stages. Besides hematological alterations, the cardiovascular system is significantly impacted by the hemodynamic effects of the disease, as persistent anemia can lead to myocardial hypoxia and the activation of inflammatory processes, potentially causing myocarditis. It is known that in dogs infected with Ehrlichia canis, there is a higher occurrence of arrhythmias and a predominance of sympathetic activity. This study assessed arrhythmogenic parameters, including P wave dispersion (Pd), QT dispersion (QTd), and QT instability, along with heart rate variability (HRV) analysis from 24 h Holter monitoring in naturally infected dogs during the acute phase (n = 10) and chronic phase (n = 10) compared to a control group (n = 10). The Pd and QTd values were higher in the infect group, confirming the arrhythmogenic character. Instability parameters (TI, LTI, and STI) were higher in sick animals, but no worsening was observed in the chronic phase. All HRV metrics in the time domain were higher in the control group, indicating a balanced sympathovagal activity throughout the day in healthy dogs. Additionally, parameters linked to parasympathetic activity (rMSSD and pNN50) were reduced in the sick groups, confirming the dominance of sympathetic activity. These findings indicate a decrease in HRV in sick individuals and reinforce this useful marker for assessing the influence of the autonomic nervous system on the cardiovascular system. In conclusion, CME exhibits arrhythmogenic activity characterized by the deterioration of predictive parameters for ventricular arrhythmias and increased activity of the sympathetic autonomic nervous system in the heart. This is likely secondary to myocarditis, myocardial hypoxia, and structural damage to cardiomyocytes. Full article

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with rare but severe cardiac manifestations, including myocarditis and pericarditis. The coexistence of SLE with sickle cell trait (SCT), an inherited hemoglobinopathy prevalent among individuals of African descent, is exceptionally rare and presents significant diagnostic challenges due to overlapping clinical features. Objective: To describe the case of an Afro-Ecuadorian male with SLE and sickle cell trait who developed an uncommon presentation of myopericarditis and pericardial effusion. Case report: A 48-year-old African American male with no prior medical history presented with persistent fever, polyarticular arthralgias, and pleuritic chest pain. Investigations revealed sickle cell trait (SCT) and myopericarditis with pericardial effusion, marking the initial manifestation of SLE. Diagnostic delays occurred due to overlapping symptoms and a family history of sickle cell disease. Laboratory findings showed elevated hemoglobin S (<50%), positive ANA (1:1280, coarse speckled pattern), and anti-Smith/RNP antibodies, meeting EULAR/ACR 2019 criteria for SLE. Cardiac MRI confirmed myopericarditis. Treatment with pulse methylprednisolone, oral prednisone, and mycophenolate mofetil resulted in clinical improvement, with stable disease control on immunomodulatory therapy during follow-up. Conclusions: This case highlights the diagnostic complexity of SLE in patients with SCT, particularly when presenting with myopericarditis as the initial manifestation. It emphasizes the importance of a comprehensive diagnostic approach and timely initiation of immunosuppressive therapy to optimize clinical outcomes. This report broadens the understanding of overlapping syndromes involving SLE and SCT. Full article

Background: Myocardial disease is an important component of the wide field of cardiovascular disease. However, the phenomenon of multiple myocardial diseases in a single patient remains understudied. Aim: To investigate the prevalence and impact of myocarditis in patients with genetic cardiomyopathies and to evaluate the outcomes of myocarditis treatment in the context of cardiomyopathies. Methods: A total of 342 patients with primary cardiomyopathies were enrolled. The study cohort included 125 patients with left ventricular non-compaction (LVNC), 100 with primary myocardial hypertrophy syndrome, 70 with arrhythmogenic right ventricular cardiomyopathy (ARVC), 60 with dilated cardiomyopathy (DCM), and 30 with restrictive cardiomyopathy (RCM). The diagnosis of myocarditis was based on data from myocardial morphological examination or a non-invasive diagnostic algorithm consisting of an analysis of clinical presentation, anti-cardiac antibody (Ab) titres, and cardiac MRI. Results: The prevalence of myocarditis was 74.3% in ARVC, 56.7% in DCM, 54.4% in LVNC, 37.5% in RCM, and 30.9% in HCM. Myocarditis had a primary viral or secondary autoimmune nature and manifested with the onset or worsening of chronic heart failure (CHF) and arrhythmias. Treatment of myocarditis in cardiomyopathies has been shown to stabilise or improve patient condition and reduce the risk of adverse outcomes. Conclusions: In cardiomyopathies, the genetic basis and inflammation are components of a single continuum, which forms a complex phenotype. In genetic cardiomyopathies, myocarditis should be actively diagnosed and treated as it is an important therapeutic target. Full article

Myocarditis is an inflammatory disease of the myocardium with heterogeneous etiology, clinical presentation, and prognosis; when it is associated with myocardial dysfunction, this identifies the entity of inflammatory cardiomyopathy. In the last few decades, the relevance of the immune system in myocarditis onset and progression has become evident, thus having crucial clinical relevance in terms of treatment and prognostic stratification. In fact, the advances in cardiac immunology have led to a better characterization of the cellular subtypes involved in the pathogenesis of inflammatory cardiomyopathy, whether the etiology is infectious or autoimmune/immune-mediated. The difference in the clinical course between spontaneous recovery to acute, subacute, or chronic progression to end-stage heart failure may be explained not only by classical prognostic markers but also through immune-pathological mechanisms at a cellular level. Nevertheless, much still needs to be clarified in terms of immune characterization and molecular mechanisms especially in biopsy-proven myocarditis. The aims of this review are to (1) describe inflammatory cardiomyopathy etiology, especially immune-mediated/autoimmune forms, (2) analyze recent findings on the role of different immune cells subtypes in myocarditis, (3) illustrate the potential clinical relevance of such findings, and (4) highlight the need of further studies in pivotal areas of myocarditis cellular immunology. Full article

Background/Objectives: Obesity is a chronic disease characterized by pathological accumulation of adipose tissue. The exponentially increasing number of children with severe obesity draws attention to the tragic consequences of the lack of, or inadequate treatment of, obesity in this age group. This article aims to present ways of preventing obesity and ways of treating its complications in order to reduce the risk of the life-threatening problems caused by it. Case Report: The first patient was a 9-year-old boy with Prader–Willi syndrome, severe obesity, obstructive sleep apnea, hypertension, status post myocarditis, and recurring episodes of desaturation up to 70–80%. Respiratory support using continuous positive airway pressure (CPAP) and two-level positive airway pressure (BiPAP) were included in the treatment and the resolution of desaturation was observed. The second patient was a 5-year-old girl with simple obesity, obstructive sleep apnea, and subclinical hypothyroidism, hospitalized for sudden cardiac arrest, most likely caused by excessive fat tissue compressing the airway. Despite the introduced treatment, tracheostomy, and tonsillectomy, the girl remained unconscious during hospitalization and in the rehabilitation clinic, where she spent 7 months in a coma. Currently, her health is slowly improving as her weight significantly decreases. In both cases, serious consequences were observed due to non-adherence to dietary recommendations, lack of regular medical check-ups, and failure to implement appropriate treatment. Conclusions: Obesity can lead to life-threatening consequences, including respiratory arrest and a need for respiratory support, if proper treatment is not administered and if medical recommendations are not followed. Full article

Background: Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis usually affects small blood vessels and is characterized by the presence of circulating autoantibodies (c-ANCA or p-ANCA). The risk of cardiovascular events is threefold higher compared to general population, and cardiac manifestations include myocarditis, pericarditis, valvulitis, aortitis, or coronary arteritis. Coronary involvement is very rare, but it is a potentially life-threatening manifestation. Methods: We present an atypical cardiac scenario of p-ANCA vasculitis. Results: A 68-year-old woman with known p-ANCA vasculitis and stage 5 chronic kidney disease (CKD) on hemodialysis presented with dizziness accompanied by low blood pressure and chest pain. Electrocardiogram on arrival showed slightly ST-T changes, with negative cardiac biomarkers and no abnormalities in cardiac regional wall motion. Five hours after presentation, the patient repeated chest pain, accompanied by a drop in blood pressure and junctional escape rhythm. The highly sensitive cardiac troponin I (hs-cTnI) was raised at 560 ng/L. Coronary angiography showed coronary arteries without significant stenosis. The provocative test with intracoronary ergonovine demonstrated coronary vasospasm of the anterior descending artery accompanied by chest pain, with resolution after intracoronary nitroglycerin. Under amlodipine, nitrate, acetylsalicylic acid, statin and corticosteroids the patient did not experience the recurrence of angina. Conclusions: This case illustrates coronary involvement, manifested as coronary spasm with favorable outcomes, in systemic vasculitis. The underlying mechanism is immune-mediated inflammation in vascular walls. Full article

Chagas disease, caused by Trypanosoma cruzi, leads to severe complications in 30% of infected individuals, including acute myocarditis and chronic fibrosing cardiomyopathy. Despite the significant burden of this disease, there is currently no licensed vaccine available to prevent it. This study aimed to evaluate the mucosal and systemic immunogenicity as well as the prophylactic efficacy of a mucosal vaccine candidate and its impact on both acute and chronic cardiomyopathy. The results showed that the nasal administration of trans-sialidase (TS) plus c-di-AMP (TS+A) vaccine elicited a NALT expression of IFN-γ, IL-17a and IL-4 mRNA as well as a nasal-specific production of IgA. An in vivo challenge with TS also triggered increased proliferation of lymphocytes from the NALT, sentinel cervical lymph node, and spleen. TS+A immunization increased the plasma levels of Th1/Th2/Th17 cytokines and elicited an evident cellular response by which to judge enhanced delayed-type hypersensitivity responses following a TS footpad challenge. After oral infection, TS+A-vaccinated mice showed significantly reduced parasitemia and parasite load in the heart, muscles and intestines, while markers of hepatic and muscle damage as well as clinical manifestations of acute infection were strongly diminished. TS+A also attenuated acute myocarditis and the expression of inflammatory markers in the heart. The protection conferred by TS+A extended into the chronic phase, where it resulted in a clear reduction in chronic myocarditis, fibrosis and functional electrocardiographic abnormalities, associated with a decreased expression of the pro-fibrotic TGF-β. These results revealed that it is possible to develop a mucosal vaccine against T. cruzi based on TS and c-di-AMP that is capable of reducing the development of Chagas cardiomyopathy, the hallmark of Chagas disease. Full article