Absence Of Myocarditis Research Articles

Routine application of cardiac magnetic resonance imaging in patients with suspected myocarditis from immune checkpoint inhibitor therapy

Abstract Background Cardiovascular adverse events including myocarditis associated with immune checkpoint inhibitor (ICI) therapy remain a challenge in clinical practice. Diagnostic assessment of ICI-related myocarditis (ICI-M) is challenging due to a variable phenotype, confounding effects and limited sensitivity of diagnostic tools. Cardiac magnetic resonance imaging (CMR) is used to diagnose non-ICI myocarditis, but evidence on diagnostic sensitivity is low, particularly in patients with a discrete phenotype. Here, we aim to assess the impact of CMR in patients with suspected ICI-related myocarditis and relate to final diagnosis including endomyocardial biopsy findings. Methods All consecutive patients receiving CMR for suspected ICI-M between September 2019 and January 2024 were included and retrospectively analysed. CMR parameters were correlated with clinical, laboratory and echocardiographic parameters and stratified for presence or absence of myocarditis as per final diagnosis. Results A total of 55 patients who received CMR for suspected ICI-related myocarditis were analysed, including 25 patients with confirmed ICI-M as per final diagnosis and 30 patients with cardiotoxicity other than myocarditis or no cardiotoxicity (ICI-O). The mean age (ICI-M versus ICI-O) was 65.7±13.6 versus (vs.) 67.3±9.9 (p=0.61) years, 32.0% vs. 26.7% (p=0.67) were female, and 40.0% vs. 26.7% (p=0.29) had pre-existing coronary heart disease. Cardiac biomarkers and echocardiographic data did not differ between the groups. In CMR analysis, presence of late gadolinium enhancement (LGE) was associated with ICI-M (56.0% vs. 26.7%, p=0.027). Myocardial oedema was generally rare and not associated with ICI-M. Endomyocardial biopsy (EMB) was used in 6 out of 55 patients (10.9%) with suspected ICI-M. In 4 of these 6 patients (66.7%) EMB confirmed ICI-M diagnosis. Of note, only 2/4 patients with EMB-confirmed myocarditis showed abnormal CMR findings. Conclusion The diagnostic assessment of ICI-M is challenged by low sensitivity of common diagnostic measures, often requiring a multimodal approach. Presence of LGE in CMR was associated with ICI-M, but sensitivity and specificity are low. Our data emphasize the high value of EMB in patients with clinically suspected ICI-M despite inconspicuous CMR. Prospective data to improve diagnostic criteria are needed.

Survival trends of extracorporeal membrane oxygenation support for pediatric emergency patients in regional and metropolitan areas in Japan

BackgroundTo assess the performance of pediatric extracorporeal membrane oxygenation (ECMO) centers, outcomes were compared between metropolitan and other areas. MethodsA retrospective cohort study was conducted at three regional centers on Kyushu Island and the largest center in the Tokyo metropolitan area of Japan. The clinical outcomes of patients of ≤15 years of age who received ECMO during 2010–2019 were investigated, targeting the survival and performance at discharge from intensive care units (ICUs), using medical charts. ResultsOne hundred and fifty-five patients were analyzed (regional, n = 70; metropolitan, n = 85). Survival rates at ICU discharge were similar between the two areas (64%). In regional centers, deterioration of Pediatric Cerebral Performance Category (PCPC) scores were more frequent (65.7% vs. 49.4%; p = 0.042), but survival rates and ΔPCPC scores (PCPC at ICU discharge–PCPC before admission) improved in the second half of the study period (p = 0.005 and p = 0.046, respectively). Veno-arterial ECMO (odds ratio [OR], 3.00; p < 0.03), extracorporeal cardiopulmonary resuscitation (OR, 8.98; p < 0.01), and absence of myocarditis (OR, 5.47; p < 0.01) were independent risk factors for deterioration of the PCPC score. A sub-analysis of patients with acute myocarditis (n = 51), the main indicator for ECMO, revealed a significantly higher proportion of cases with deteriorated PCPC scores in regional centers (51.9% vs. 25.0%; p = 0.049). ConclusionsThe survival rates of pediatric patients supported by ECMO in regional centers were similar to those in a metropolitan center. However, neurological outcomes must be improved, particularly in patients with acute myocarditis.

Cardiac autopsy findings in patients with COVID-19

Coronavirus disease 2019 (COVID-19) infection was first discovered in December 2019 and was soon declared a worldwide pandemic. With the decrease in the severity of the deadly disease, there is a false sense of relief globally. However, there has been an increasing trend in the cases of cardiovascular and other complications of COVID-19 which has raised concern about the sequelae of this infection. The number of cases of sudden cardiac death and myocardial infection, post-COVID-19 has seen a major leap, especially in healthy people of both genders. Systemic comorbidities and immunocompromised states have a direct effect on the prognosis of patients. The SARS-CoV-2 infection not just affects the respiratory system but multi-organ involvement is seen due to this deadly virus. The heart is a vital organ that has acute- acute and long-term consequences, what is known as long-COVID, which lead to increased morbidity and mortality. There are increased cases of multiple cardiovascular problems such as blood clots, cardiovascular accidents, myocarditis, myocardial infarction, and heart failure in people after recovering from SARS-CoV-2 infection. The histopathological findings in the heart due to COVID-19 infection can be interstitial edema with the presence or absence of myocarditis, lymphocytic endotheliitis, microvascular microthrombi, thrombosis, interstitial fibrosis with no endothelins, or rarely myocarditis. While the tissue diagnosis during acute illness is less likely feasible, autopsy findings can be helpful to understand better pathophysiology of the disease and thus help in the better management of the patient. This review was performed to analyze the postmortem findings of the heart in patients infected with the SARS-COV-2 virus, to understand the effect of COVID-19 and its complications on the heart. The pathological changes in the cardiovascular system need to be explained and correlated with the clinical findings and prognosis of the patients. We also want to hypothesize that these findings, especially myocarditis lead to sudden death in the young, which gets undetected on routine investigations.

Predictive factors of recurrence after pediatric acute pericarditis

ObjectiveThe predisposing factors for pericarditis recurrence in the pediatric population have not yet been established. This study aimed to define the risk factors for the unfavorable prognosis of pediatric acute pericarditis. MethodsThis was a retrospective study that included all patients with acute pericarditis treated from 2011 to 2019 at a tertiary referent pediatric center. ResultsThe study included 72 children. Recurrence was observed in 22.2% patients. Independent risk factors for recurrence were: erythrocyte sedimentation rate≥50mm/h (p=0.003, OR 186.3), absence of myocarditis (p=0.05, OR 15.2), C-reactive protein≥125mg/L (p=0.04, OR 1.5), and non-idiopathic etiology pericarditis (p=0.003, OR 1.3). Corticosteroid treatment in acute pericarditis was associated with a higher recurrence rate than treatment with non-steroid anti-inflammatory therapy (p=0.04). Furthermore, patients treated with colchicine in the primary recurrence had lower recurrence rate and median number of repeated infections than those treated without colchicine (p=0.04; p=0.007, respectively). ConclusionIndependent risk factors for recurrence are absence of myocarditis, non-idiopathic etiology pericarditis, C-reactive protein≥125mg/L, and erythrocyte sedimentation rate≥50mm/h. Acute pericarditis should be treated with non-steroid anti-inflammatory therapy. A combination of colchicine and non-steroid anti-inflammatory drugs could be recommended as the treatment of choice in recurrent pericarditis.

Temporal Trends in the Clinical and Pathological Characteristics of Victims of Sudden Cardiac Death in the Absence of Previously Identified Heart Disease.

Coronary artery disease is identified in ≈80% of victims of sudden cardiac death (SCD). Because the prevention strategies and public awareness have changed during the past decades, we studied the temporal trends in the pathogenesis of SCD. FinGesture (n=4031) is a prospective study designed to classify the phenotype and genotype profiles of SCD in a consecutive series of victims of SCD in Northern Finland. On the basis of Finnish law, all subjects who die suddenly undergo autopsy. We analyzed the characteristics of SCD victims and autopsy findings in 1998 to 2002, 2003 to 2007, and 2008 to 2012. Among victims of SCD as a first cardiac event (n=2697), the proportion with coronary artery disease decreased during the 2008 to 2012 time period, compared with the 2 preceding 5-year periods: 74.0% in 1998 to 2002, 73.1% in 2003 to 2007, and 66.4% in 2008 to 2012 (P<0.001). Proportion of SCDs associated with hypertensive heart disease with left ventricular hypertrophy in the absence of coronary artery disease increased from 1.7% in 1998 to 2002 to 5.8% in 2003 to 2007 and 8.9% in 2008 to 2012 (P<0.001). Similarly, myocardial fibrosis in the absence of myocarditis or left ventricular hypertrophy, or other known pathogeneses, was 6.7% in the past 5-year period compared with 2 previous 5-year periods (3.7% and 4.0%; P<0.001 between 1998-2002 and 2008-2012 and between 2003-2007 and 2008-2012). The proportion of SCDs attributable to coronary artery disease, in the absence of a history of heart disease, has decreased, whereas the proportion associated with hypertensive heart disease and idiopathic fibrosis has increased during the past 15 years.

Inflammatory response to clozapine in the absence of myocarditis: case report.

SummaryA case is presented of a 25-year-old man with treatment-resistant paranoid schizophrenia whose only previous trial of clozapine had been stopped following a suspected clozapine-induced myocarditis. Due to the failure of his psychosis to respond to a number of antipsychotic treatments and augmentation strategies, clozapine was restarted on admission. His rechallenge was marked by intermittent pyrexia, tachycardia and elevated C-reactive protein (CRP), but eosinophilia was absent. Clozapine was started and then stopped twice following extensive investigation and with specialist cardiology consultation. Physical symptoms and CRP elevation resolved shortly after clozapine cessation. We believe this constituted an idiosyncratic systemic inflammatory response to clozapine treatment.Declaration of interestNone.Copyright and usage© The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Pathogenic Potential of Trypanosoma cruzi-Induced Autoimmunity (93.2)

Abstract Chagas heart disease (CHD), caused by the parasite Trypanosoma cruzi, is a potentially fatal myocarditis associated with cardiac autoimmunity. Immunization of A/J mice with heat-killed T. cruzi (HKTC) induces acute cardiac damage and polyantigenic humoral and cellular autoimmunity of a specificity and magnitude similar to that observed in infected mice, yet it does not cause cardiac inflammation. The goal of the present study was to determine the differences between the autoimmune response induced by T. cruzi infection and that initiated by HKTC immunization that may be responsible for the presence or absence of myocarditis. We hypothesized that certain inflammatory conditions or secondary immune stimuli might be required in order for T. cruzi-induced autoimmunity to lead to myocarditis. The antigen specificity, autoantibody titers, and DTH responses to a panel of known cardiac autoantigens were similar in infected and HKTC-immunized mice. However, the HKTC-immunized mice failed to develop the robust Th1/Th17-mediated immune response present in infected mice. This suggested that Th1/Th17 responses may be important for the development of myocarditis associated with live T. cruzi infection. Coadministration of Th1-promoting but not Th2-promoting adjuvants resulted in the development of myocarditis in HKTC-immunized mice, supporting this hypothesis.

Myocarditis and long-term survival in peripartum cardiomyopathy

Background The reported mortality rate of peripartum cardiomyopathy (PPCM) is high, although the potential for spontaneous recovery of ventricular function is well established. The prevalence of myocarditis in PPCM has varied widely between studies. The purposes of this study were to define the long-term prognosis in a referral population of patients with PPCM, to determine the prevalence of myocarditis on endomyocardial biopsy in this population, and to identify clinical variables associated with poor outcome. Methods We analyzed clinical, echocardiographic, hemodynamic, and histologic features of 42 women with PPCM evaluated at our institution over a 15-year period. Each patient underwent an extensive evaluation, including echocardiography, endomyocardial biopsy, and right heart catheterization. Data were analyzed to identify features at initial examination associated with the combined end point of death or cardiac transplantation by the use of Kaplan-Meier survival curves and a Cox proportional hazards model. Results Three (7%) patients died and 3 (7%) patients underwent heart transplantation during a median follow-up of 8.6 years. Endomyocardial biopsy demonstrated a high prevalence of myocarditis (62%), but the presence or absence of myocarditis was not associated with survival. Of the prespecified variables assessed, only decreased left ventricular stroke work index was associated with worsened outcome. Conclusions In patients with PPCM, (1) long-term survival is better than has been historically reported, (2) the prevalence of myocarditis is high, and (3) decreased left ventricular stroke work index is associated with worse clinical outcomes. (Am Heart J 2000;140:785-91.)

Endomyocardial biopsy findings in cases with pericarditis or perimyocarditis

In order to determine the presence or absence of myocarditis in cases with viral or idiopathic pericarditis, a study was conducted as one of our series on endomyocardial biopsy. There were two groups of patients, pericarditis cases (n = 8), and patients with perimyocarditis (n = 6). In the former group, it was confirmed that cardiac sarcoplasmic enzymes were not released during the acute stage of the disease. In the latter, there was positive evidence of the enzyme release. Also, employing our method of categorizing the possibility of myocarditis at the histopathological level, we found that the category 'highly suggestive' of myocarditis was absent in all eight cases with pericarditis. However, in cases with perimyocarditis, this category was assigned in four out of six cases (67%), indicating a high incidence. The category, 'slightly suggestive', was seen in three cases of the former (38%) and two cases of the latter group (33%). It is concluded that in patients with pericarditis, the release of cardiac sarcoplasmic enzyme is an important diagnostic element in the diagnosis of perimyocarditis even if the clinical features reveal a predominance of pericarditis. In patients with perimyocarditis, progression to residual cardiac disease, such as conduction disturbance or congestive heart failure, is likely.

Influence of dilated cardiomyopathy, myocarditis and cardiac transplantation on the relation between plasma atrial natriuretic factor and atrial pressures

To determine whether dilated cardiomyopathy, myocarditis or cardiac transplantation affect the relation between plasma immunoreactive atrial natriuretic factor (ANF) and cardiac filling pressures, right atrial plasma ANF concentration, pulmonary arterial wedge pressure and right atrial pressure were measured in patients with dilated cardiomyopathy (n = 48), dilated cardiomyopathy secondary to myocarditis (n = 20) and prior cardiac transplantation (n = 34). ANF level significantly correlated with both pulmonary arterial wedge and right atrial pressures in patients with dilated cardiomyopathy; however, the presence or absence of myocarditis did not significantly alter these relations (p = 0.88 and p = 0.33 for interaction terms, respectively). For the combined group the ANF-pulmonary arterial wedge pressure relation had a slope of 8.1 pg/ ml/mm Hg (95% confidence interval (CI), 5.4 to 10.8; p = 0.0001) and the ANF-right atrial pressure relation a slope of 13.6 pg/ml/mm Hg (CI, 8.5 to 18.7; p = 0.0001). Receiver operator curve analysis identified an optimal dividing point of ANF 150 pg/ml with 100% (CI, 72 to 100%) of patients with right atrial pressure ≥ 8 mm Hg having ANF ≥ 150 pg/ml, but only 56% (CI, 42 to 69%) with pressure < 8 mm Hg having ANF < 150 pg/ml. Unlike the patients with cardiomyopathy (with or without myocarditis), cardiac transplant recipients displayed no correlation between ANF level and either pulmonary arterial wedge pressure (p = 0.50) or right atrial pressure (p = 0.29) despite similarly elevated ANF concentrations (mean ± standard deviation, 168 (83) pg/ml in transplant patients versus 185 (114) pg/ml in cardiomyopathy patients). It is concluded that left and right intracardiac pressures are important determinants of circulating ANF level unaffected by inflammation in patients with cardiomyopathy. Factors other than filling pressures influence circulating ANF in a significant number of patients with cardiomyopathy and in all transplant recipients.

Left ventricular abnormality with late mitral insufficiency and abnormal electrocardiogram

An abnormal contraction that alters the contour of the left ventricle only during systole but not in diastole and results in mild mitral insufficiency has been demonstrated in 6 girls with apical systolic click, late systolic murmur and T wave inversion. They have remained asymptomatic during a period of follow-up studies ranging from 3 to 17 years. Their young age and the absence of myocarditis, pericarditis and coronary arterial abnormality suggest that they have a congenital anomaly in a localized area of the left ventricular myocardium which results in late systolic dysfunction of the mitral apparatus. We believe that the findings in this group constitute a distinctive syndrome among the heterogeneous causes of mitral insufficiency late in systole.