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MedRxiv : the Preprint Server For... Jun 2024Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process...
BACKGROUND
Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this 'cardiomyotoxicity' are lacking.
METHODS
A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated.
RESULTS
In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score=4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events.
CONCLUSIONS
ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well.
PubMed: 38883792
DOI: 10.1101/2024.06.02.24308336 -
Journal of the American Heart... Jun 2024Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic... (Review)
Review
Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic value for cardiac diseases. However, heterophile antibodies, antitroponin antibodies, and macrotroponin complexes can be observed both in seemingly healthy individuals and patients with cardiac diseases, potentially leading to false positive or disproportionate elevation of cTn (cardiac troponin) assay results and introducing discrepancies in clinical interpretations with impact on medical management. In this review article, we describe the possible mechanisms of cTn release and the sources of variations in the assessment of circulating cTn levels. We also explore the pathophysiological mechanisms underlying antitroponin antibody development and discuss the influence exerted by macrotroponin complexes on the results of immunoassays. Additionally, we explore approaches to detect these complexes by presenting various clinical scenarios encountered in routine clinical practice. Finally, unsolved questions about the development, prevalence, and clinical significance of cardiac autoantibodies are discussed.
Topics: Humans; Biomarkers; Autoantibodies; Heart Diseases; Predictive Value of Tests; Troponin I; Prognosis
PubMed: 38879450
DOI: 10.1161/JAHA.123.035128 -
Cureus May 2024Immune checkpoint inhibitors (ICIs) are a form of immunotherapy increasingly utilized in cancer therapies. While offering promise in malignancy treatment, ICIs,...
Immune checkpoint inhibitors (ICIs) are a form of immunotherapy increasingly utilized in cancer therapies. While offering promise in malignancy treatment, ICIs, including atezolizumab, can elicit immune-related adverse events (irAEs) such as cardiotoxicity. We present the case of a 67-year-old male with stage IV metastatic small-cell lung cancer undergoing carboplatin, etoposide, and atezolizumab therapy, who developed pericardial tamponade two months into treatment. Initially presenting with hypoxia on day three of his third treatment cycle, he was admitted due to multifocal pneumonia and subsequently diagnosed with pericardial tamponade stemming from a sizable pericardial effusion. Pericardiocentesis was performed, effectively resolving the tamponade. Infectious etiology was ruled out. Notably, there was no associated myocarditis, as evidenced by negative cardiac markers and magnetic resonance imaging (MRI) findings, and cytologic analysis of the pericardial fluid did not reveal malignant cells, indicating an isolated immunologic etiology for the pericardial effusion. Following successful management, including oxygen support and a prednisone taper, chemotherapy without immunotherapy was resumed after a one-week delay. This rare case underscores the significance of promptly utilizing multimodality imaging with timely cardiology intervention, a prompt pericardial fluid analysis in diagnosing cardiac irAEs, and management leading to improved patient outcomes.
PubMed: 38868282
DOI: 10.7759/cureus.60184 -
European Heart Journal. Case Reports Jun 2024Acute myocarditis (AM) is an inflammatory heart disease that may occur as a consequence of autoimmune disorders. Although the correlation between myocarditis and...
Acute lymphocytic myocarditis characterized by cardiogenic shock and conduction system abnormalities in patients with Hashimoto's thyroiditis: a case report and review of literature.
BACKGROUND
Acute myocarditis (AM) is an inflammatory heart disease that may occur as a consequence of autoimmune disorders. Although the correlation between myocarditis and hyperthyroidism has been reported in the literature, the association with hypothyroidism is less frequent.
CASE SUMMARY
We describe a characteristic case of lymphocytic acute myocarditis deteriorated into cardiogenic shock due to Hashimoto's thyroiditis treated with vasopressor and inotropic drugs in combination with corticosteroid. On admission, electrocardiography revealed a sinus tachycardia with 1st degree atrioventricular (AV) block, right bundle branch block (RBBB), and left anterior fascicular block. Laboratory tests demonstrated a severe hypothyroidism and high-titre serum of antibodies against thyroglobulin. She presented a favourable clinical course, restoring haemodynamic stability. A resolution of hypothyroidism and a progressive reduction of the value of antibodies against thyroglobulin occurred. On Day 35, the patient was discharged showing on electrocardiogram the occurrence of left posterior fascicular block, disappearance of 1st degree AV block and partial improvement of RBBB along with the normalization of the left ventricular contractility abnormalities on echocardiography.
DISCUSSION
Autoimmune features, mostly Hashimoto's thyroiditis, are associated in lymphocytic acute myocarditis to a worse prognosis and an increased risk of recurrence. More studies are needed to elucidate the underlying mechanism.
PubMed: 38868158
DOI: 10.1093/ehjcr/ytae268 -
European Heart Journal Supplements :... Apr 2024In the ESC 2023 guidelines, cardiomyopathies are conservatively defined as 'myocardial disorders in which the heart muscle is structurally and functionally abnormal, in...
In the ESC 2023 guidelines, cardiomyopathies are conservatively defined as 'myocardial disorders in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease sufficient to cause the observed myocardial abnormality'. They are morpho-functionally classified as hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular cardiomyopathy with the addition of the left ventricular non-dilated cardiomyopathy that describes intermediate phenotypes not fulfilling standard disease definitions despite the presence of myocardial disease on cardiac imaging or tissue analysis. The new ESC guidelines provide 'a guide to the diagnostic approach to cardiomyopathies, highlight general evaluation and management issues, and signpost the reader to the relevant evidence base for the recommendations'. The recommendations and suggestions included in the document provide the tools to build up pathways tailored to specific cardiomyopathy (phenotype and cause) and define therapeutic indications, including target therapies where possible. The impact is on clinical cardiology, where disease-specific care paths can be assisted by the guidelines, and on genetics, both clinics and testing, where deep phenotyping and participated multi-disciplinary evaluation provide a unique tool for validating the pathogenicity of variants. The role of endomyocardial biopsy remains underexploited and confined to particular forms of restrictive cardiomyopathy, myocarditis, and amyloidosis. New research and development will be needed to cover the gaps between science and clinics. Finally, the opening up to disciplines such as bioinformatics, bioengineering, mathematics, and physics will support clinical cardiologists in the best governance of the novel artificial intelligence-assisted resources.
PubMed: 38867869
DOI: 10.1093/eurheartjsupp/suae002 -
Cardiovascular Pathology : the Official... Jun 2024A 64-year-old woman with a history of subarachnoid hemorrhage, breast cancer, cervical spine tumor, and syringomyelia developed recurrent pericardial effusion and...
A 64-year-old woman with a history of subarachnoid hemorrhage, breast cancer, cervical spine tumor, and syringomyelia developed recurrent pericardial effusion and cardiac tamponade after receiving the third dose of coronavirus disease 2019 mRNA vaccine, mRNA-1273 (Spikevax, Moderna). The cardiac tamponade of unknown etiology was intractable with nonsteroidal anti-inflammatory drugs, colchicine, and prednisolone. She underwent thoracoscopic pericardiectomy, and microthrombi were detected in the pericardial tissue. Although the exact causal relationship between vaccination and recurrent cardiac tamponade was unclear, the vaccine possibly caused or triggered the microthrombi formation, resulting in recurrent cardiac tamponade. Because of the potential for cardiovascular side effects such as thrombosis and myocarditis following vaccination, it was deemed necessary to accumulate and analyze such cases.
PubMed: 38866088
DOI: 10.1016/j.carpath.2024.107668 -
Journal of Infection in Developing... May 2024Coenzyme Q10 (CoQ10) is considered to be beneficial for patients with acute viral myocarditis (AVM). In addition, trimetazidine may be also beneficial to patients with... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Coenzyme Q10 (CoQ10) is considered to be beneficial for patients with acute viral myocarditis (AVM). In addition, trimetazidine may be also beneficial to patients with AVM by promoting cardiac energy metabolism. This systematic review and meta-analysis examined the efficacy and safety of combining trimetazidine and CoQ10 with respect to CoQ10 alone in patients suffering from AVM.
METHODOLOGY
PubMed, Embase, the Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched for relevant randomized controlled trials (RCTs). An analysis of random effects was employed to combine the results.
RESULTS
Sixteen RCTs that included 1,364 patients with AVM contributed to the meta-analysis. Overall, 687 patients received the combined treatment, while 677 received the CoQ10 alone for a duration of 2-12 weeks (mean: 5.2 weeks). In contrast to monotherapy with CoQ10, combined treatment with trimetazidine and CoQ10 significantly improved overall therapy effectiveness (risk ratio [RR]: 1.19, 95% confidence interval [CI]: 1.13 to 1.24, p < 0.001; I2 = 0%). Differences in study parameters such as the incidence of heart failure upon admission, dosage of CoQ10, or length of treatment did not significantly alter the outcomes (p for all subgroup analyses > 0.05). The combined treatment was associated with improved myocardial enzyme levels and recovery of cardiac systolic function as compared to CoQ10 alone (p all < 0.05). In addition, trimetazidine combined with CoQ10 caused no greater increase in adverse events than CoQ10 alone.
CONCLUSIONS
Trimetazidine combined with CoQ10 is an effective and safe treatment for AVM.
Topics: Trimetazidine; Humans; Myocarditis; Ubiquinone; Drug Therapy, Combination; Randomized Controlled Trials as Topic; Treatment Outcome; Acute Disease
PubMed: 38865387
DOI: 10.3855/jidc.18776 -
Pharmacology Research & Perspectives Jun 2024Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China in 2019. Soon after, it was declared a... (Review)
Review
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China in 2019. Soon after, it was declared a pandemic by the World Health Organization. The health crisis imposed by a new virus and its rapid spread worldwide prompted the fast development of vaccines. For the first time in human history, two vaccines based on recombinant genetic material technology were approved for human use. These mRNA vaccines were applied in massive immunization programs around the world, followed by other vaccines based on more traditional approaches. Even though all vaccines were tested in clinical trials prior to their general administration, serious adverse events, usually of very low incidence, were mostly identified after application of millions of doses. Establishing a direct correlation (the cause-effect paradigm) between vaccination and the appearance of adverse effects has proven challenging. This review focuses on the main adverse effects observed after vaccination, including anaphylaxis, myocarditis, vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, and transverse myelitis reported in the context of COVID-19 vaccination. We highlight the symptoms, laboratory tests required for an adequate diagnosis, and briefly outline the recommended treatments for these adverse effects. The aim of this work is to increase awareness among healthcare personnel about the serious adverse events that may arise post-vaccination. Regardless of the ongoing discussion about the safety of COVID-19 vaccination, these adverse effects must be identified promptly and treated effectively to reduce the risk of complications.
Topics: Humans; COVID-19 Vaccines; COVID-19; Incidence; Vaccination; Anaphylaxis; SARS-CoV-2; Guillain-Barre Syndrome; Myocarditis
PubMed: 38864106
DOI: 10.1002/prp2.1224 -
Clinical Case Reports Jun 2024Immune checkpoint inhibitors can rarely lead to occurrence of myositis, myocarditis, and myasthenia gravis (MG). Early recognition and multidisciplinary management are...
KEY CLINICAL MESSAGE
Immune checkpoint inhibitors can rarely lead to occurrence of myositis, myocarditis, and myasthenia gravis (MG). Early recognition and multidisciplinary management are crucial for optimal outcomes. Vigilance for overlapping toxicities is essential in patients receiving combination immunotherapy.
ABSTRACT
The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, but it is associated with immune-related adverse events (IRAEs) affecting various organ systems. The simultaneous occurrence of MG, myocarditis, and myositis highlights the complex nature of IRAEs. Early recognition and comprehensive multidisciplinary management are crucial for optimal patient outcomes. We present a unique case report of a 76-year-old male patient with advanced melanoma who developed concurrent myositis, myocarditis, and MG while receiving combination immunotherapy with Nivolumab and Ipilimumab. This case underscores the significance of recognizing and addressing the "Terrible Triad" of IRAEs in patients receiving ICIs. Healthcare providers should maintain a high index of suspicion for overlapping toxicities and promptly initiate appropriate interventions.
PubMed: 38863868
DOI: 10.1002/ccr3.8968 -
Cardio-oncology (London, England) Jun 2024Immune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated...
PURPOSE
Immune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated the immune status and characteristics of patients diagnosed with ICIs- associated myocarditis.
METHODS
A total of seven patients diagnosed with ICIs-associated myocarditis were included in the study, while five tumor patients without myocarditis were recruited as reference controls. Additionally, 30 healthy individuals were recruited as blank controls. Biochemical indices, electrocardiogram, and echocardiography measurements were obtained both prior to and following the occurrence of myocarditis. High-throughput sequencing of T cell receptor (TCR) was employed to assess the diversity and distribution characteristics of TCR CDR3 length, as well as the diversity of variable (V) and joining (J) genes of T lymphocytes in peripheral blood.
RESULTS
In the seven patients with ICIs-associated myocarditis, Troponin T (TNT) levels exhibited a significant increase following myocarditis, while other parameters such as brain natriuretic peptide (BNP), QTc interval, and left ventricular ejection fraction (LVEF) did not show any significant differences. Through sequencing, it was observed that the diversity and uniformity of CDR3 in the ICIs-associated myocarditis patients were significantly diminished. Additionally, the distribution of CDR3 nucleotides deviated from normality, and variations in the utilization of V and J gene segments.
CONCLUSION
The reconstitution of the TCR immune repertoire may play a pivotal role in the recognition of antigens in patients with ICIs-associated myocarditis.
PubMed: 38863010
DOI: 10.1186/s40959-024-00230-4