T lymphocytes are increasingly recognized as central regulators of cardiac inflammation, contributing to both tissue repair and disease progression across conditions such as myocardial infarction, heart failure, and myocarditis. While traditionally viewed as transient responders to injury, emerging evidence indicates that cardiac T cell responses are often antigen-driven, clonally expanded, and sustained over time. In particular, α-myosin heavy chain (α-MyHC, encoded by MYH6) has emerged as a dominant cardiac autoantigen capable of eliciting pathogenic T cell responses in both experimental models and human disease. In parallel, tissue-resident memory T cells (Trm) have been established as a distinct population of memory T cells that persist within non-lymphoid tissues and provide rapid, localized responses upon antigen re-exposure. Although extensively studied in non-lymphoid and barrier tissues, Trm are now increasingly implicated in chronic inflammatory and autoimmune diseases, where they can act as long-lived reservoirs of antigen-experienced T cells. Here, we propose that cardiac injury seeds antigen-specific T cell populations that acquire tissue-resident phenotypes within the myocardium, thereby linking acute immune activation to chronic, relapsing inflammation. We first review the role of T cells in cardiac homeostasis, aging, and disease, highlighting features of antigen specificity, persistence, and local adaptation. We then outline the defining characteristics and developmental pathways of Trm and integrate emerging evidence for their presence and function in the heart. Particular emphasis is placed on α-MyHC-specific Trm as potential drivers of cardiac autoimmunity and immune-related adverse events of cancer immunotherapies, including immune checkpoint inhibitor-associated myocarditis. Finally, we discuss the implications of this framework for understanding chronic cardiac inflammation and for developing therapeutic strategies targeting tissue-resident immune populations.

Background Cardiac sarcoidosis (CS) may present with conduction abnormalities, ventricular arrhythmias, and heart failure. The delay in recognizing cardiac involvement in systemic sarcoidosis leads to disease progression, resulting in major morbidity and mortality. We studied the clinical, electrocardiographic, and imaging features of cardiac sarcoidosis and its mortality predictors. Methods The clinical data of patients with CS who presented to the Sree Chitra Tirunal Institute for Medical Sciences and Technology between 2005 and 2021 were retrospectively analysed. The diagnosis of CS was based on the 2014 Heart Rhythm Society Expert Consensus recommendations and the 2016 Japanese Circulation Society clinical diagnosis criteria. Patients with obstructive coronary artery disease and possible myocarditis were excluded from the study. Results Forty-three patients of CS (31 males), aged 49 (8.8) years, were followed up for a mean duration of 4.3 (range 1.87-6.5) years. The presenting clinical manifestations were ventricular tachycardia (VT) 14/43 (33%), acute heart failure 14/43 (33%), complete heart block 10/43 (23%), and non-sustained VT/symptomatic ventricular premature complexes 2/43 (5%). Systemic manifestations included lymphadenopathy 28/43 (65%), pulmonary parenchymal involvement 26/43 (60%), and neurological involvement 8/43 (19%). The mean basal left ventricular ejection fraction at presentation was 41.1% (standard deviation 16.1%), and 31/33 (94%) of the patients had late gadolinium enhance-ment in cardiac MRI, with the predominant pattern being sub-epicardial 18/33 (58%) or mid-myocardial 17/33 (54%). Eighteen (42%) patients received implantable cardioverter defibrillator (ICD); nearly half had appropriate ICD shocks. On follow-up, 11 (25%) patients died, 10 (23%) had recurrent heart failure admissions, and 5 (29%) had recurrent ICD shocks. Multivariate analysis revealed higher New York Heart Association (NYHA) class/clinical heart failure at presentation, elevated erythrocyte sedimentation rate at diagnosis, and persistent low ejection fraction during follow-up to be predictors of mortality, not VT. Survival analysis showed that recurrent heart failure admissions predict early mortality. Conclusion Although arrhythmia was the most common manifestation, clinical heart failure was seen in nearly half of the patients with a diagnosis of CS. A high prevalence of heart failure, along with 25% mortality in our study, may indicate a delayed recognition of cardiac involvement in these patients' natural history. Recurrent heart failure admissions predicted early mortality.

Canine parvovirus (CPV) is a highly contagious disease, typically causing haemorrhagic enteritis in dogs. The myocardial form, though well-documented historically, is now rare in vaccinated canine populations. This case report describes the first confirmed outbreak of acute parvoviral myocarditis in one-day-old German shepherd puppies in Iran. A litter of six neonates from a reportedly vaccinated primiparous bitch presented with acute lethargy, refusal to nurse, hypothermia and respiratory distress. Despite supportive medical care, all puppies died within hours. Postmortem examination revealed cardiomegaly with pale myocardial streaks, pulmonary consolidation and thymic haemorrhage. Histopathological analysis of heart tissue identified lymphoplasmacytic myocarditis with intranuclear inclusion bodies. Polymerase chain reaction (PCR) performed on cardiac tissue confirmed the presence of CPV. This case underscores that the cardiac form of CPV remains a threat to neonates, likely due to in utero or perinatal infection in the absence of maternal immunity. This case also serves as a reminder that CPV myocarditis can have a delayed clinical course, with heart failure and death occurring weeks to months after initial infection. Although CPV myocarditis can have a delayed clinical course, with heart failure and death occurring weeks to months after initial infection, this case underscores that the cardiac form of CPV remains a threat to neonates, likely due to in utero or perinatal infection in the absence of maternal immunity. It highlights the critical importance of ensuring complete and timely vaccination of breeding bitches and the need for vigilance regarding this rare but fatal manifestation of CPV.

Myocarditis is an underrecognized cause of malignant ventricular arrhythmias, particularly in young adults with preserved cardiac structure on initial evaluation. We report a 37-year-old previously healthy man who presented with hemodynamically unstable ventricular tachycardia accompanied by significant troponin elevation but normal coronary arteries and preserved left ventricular systolic function on echocardiography. The arrhythmia initially mimicked idiopathic fascicular ventricular tachycardia. Cardiac magnetic resonance imaging subsequently revealed subepicardial late gadolinium enhancement and myocardial edema, establishing the diagnosis of acute myocarditis as the arrhythmogenic substrate. Therapy was adjusted with good clinical stability and no recurrence of arrhythmia. This case underscores the diagnostic challenges and the value of cardiac magnetic resonance imaging in unexplained ventricular tachycardia and emphasizes the importance of thorough history followed by etiology-directed management in myocarditis-related arrhythmias, and that clinicians must maintain a high index of suspicion for myocarditis in similar presentations.

In murine coxsackievirus B3 myocarditis, the most widely used experimental model of viral myocarditis, functional alterations such as reduced cardiac output are frequently interpreted as surrogates of myocardial injury and inflammation, despite concurrent systemic illness. The relative contribution of systemic disease processes to these functional changes remains poorly defined. We therefore aimed to disentangle myocardial and systemic drivers of cardiac dysfunction using a microRNA-guided viral detargeting approach. We engineered a cardiomyocyte-detargeted virus by inserting target sequences for the muscle-enriched microRNA-1 into the viral genome, selectively suppressing viral replication in cardiac muscle while largely preserving systemic infection. This enabled direct comparison between conventional myocarditis and cardiac-attenuated infection in mice, using serial echocardiography as the primary non-invasive functional readout of cardiac performance. Day 3 post infection was analyzed as the acute phase and day 7 as a later stage associated with peak myocardial inflammation. Cardiac viral titers were profoundly reduced by detargeting (approximately 3-log at day 3 and 6-7-log at day 7), accompanied by absence of troponin T release, inflammatory cell infiltration, and histological myocarditis. Despite this, cardiac output was reduced at day 3 and remained impaired at day 7 in both groups. This reduction was associated with decreased left ventricular end-diastolic volume, while ejection fraction remained preserved. At day 3, additional reductions in cardiac output and global longitudinal strain were observed in control-virus-infected mice. At day 7, cardiac output remained comparably reduced despite marked differences in myocardial injury. These findings demonstrate that systemic infection substantially contributes to impaired cardiac function and that echocardiographic readouts reflect a composite phenotype. Functional alterations should therefore be interpreted in the context of systemic effects and integrated with cross-organ analyses to enable accurate interpretation in preclinical myocarditis models.

Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is an ultra-rare, fatal autosomal recessive disorder caused by ASAH1 mutations, with no curative treatment. We report the first-in-human intravenous administration of an AAV9 vector carrying the human ASAH1 coding sequence in a 15-year-old female with advanced SMA-PME (heterozygous ASAH1 c.456A>C and c.918-2A>G mutations). The patient presented with severe neuromuscular impairment, deafness, and recurrent myoclonic status epilepticus, without detectable anti-AAV9 neutralizing antibodies. A marked clinical deterioration warranted compassionate use (GNT-017-ASAH-CU). A dose of 2.2×10[14] vector genomes per kilogram of body weight was administered under prophylactic prednisolone and sirolimus. The patient experienced rapid onset of complement activation leading to a cytokine-mediated capillary leak syndrome, culminating in refractory shock, multiorgan failure, and death on day eight. A postmortem examination revealed acute circulatory failure as the cause of death without myocarditis or thrombotic microangiopathy Some endothelial injury was suggested by a rise in von Willebrand factor from days 4-8, paralleled by increased hyaluronic acid on days 7-8. These findings underscore the potential for life-threatening innate immune activation in patients with advanced SMA-PME receiving high-dose systemic AAV9 gene therapy, highlighting the need to identify high-risk patients and proactively monitor biomarkers of endothelial injury.

Leptospirosis is a zoonotic infection predominantly affecting marginalized populations in tropical regions, often resulting from exposure to contaminated water or contact with animal reservoirs, especially rodents. The disease typically manifests in a biphasic nature; beginning with an incubation period ranging from several days to a few weeks, followed by a septicaemic phase, an interphase where symptoms resolve temporarily, and finally an immune phase. While most infections are mild, approximately 10% progress to severe disease involving multi-organ complications, typically manifesting during the immune phase. We report a case of myocarditis and septic shock during the acute phase of leptospirosis.

Encephalomyocarditis virus (EMCV), an important zoonotic pathogen, causes an acute disease characterized primarily by encephalitis and myocarditis. Interferon (IFN) activates the JAK-STAT signaling pathway to induce the expression of interferon-stimulated genes (ISGs), resulting in antiviral effects. However, the mechanism through which EMCV evades the immune system via the IFN-mediated JAK-STAT signaling pathway remains poorly understood. Here, we identified an E3 ubiquitin ligase, RNF149, that is upregulated in EMCV-infected cells. Overexpression of RNF149 inhibited type I IFN-mediated JAK-STAT signaling pathway activation and its antiviral response, enhancing viral replication. Knockout of RNF149 promoted ISGs expression. Notably, RNF149 interacted with JAK1 and downregulated its protein expression through the E3 ubiquitin ligase. RNF149 promoted the K27- and K33-linked ubiquitination of JAK1, which promoted JAK1 degradation through the proteasome pathway. Taken together, these data describe a negative regulatory mechanism involving RNF149 in interferon antiviral activity and provide insights into the mechanism by which EMCV evades host antiviral immunity. These results provide a new strategy for treating viral infections.