Diagnostic accuracy, clinical characteristics, and prognostic differences of patients with acute myocarditis according to inclusion criteria.

INTRODUCTION: The diagnosis of acute myocarditis (AM) is complex due to its heterogeneity and typically is defined by either Electronic Healthcare Records (EHRs) or advanced imaging and endomyocardial biopsy, but there is no consensus. We aimed to investigate the diagnostic accuracy of these approaches for AM. METHODS: Data on ICD 10th Revision(ICD-10) codes corresponding to AM were collected from two hospitals and compared to CMR-confirmed or clinically suspected(CS) AM cases with respect to diagnostic accuracy, clinical characteristics, and all-cause mortality. Next, we performed a review of published AM studies according to inclusion criteria. RESULTS: We identified 291 unique admissions with ICD-10 codes corresponding to AM in the first three diagnostic positions. The positive predictive value(PPV) of ICD-10 codes for CMR-confirmed or CS-AM was 36%, and patients with CMR-confirmed or CS AM had a lower all-cause mortality than those with a refuted diagnosis (P = 0.019). Using an unstructured approach, patients with CMR-confirmed and CS AM had similar demographics, comorbidity profiles and survival over a median follow-up of 52 months (P = 0.72). Our review of the literature confirmed our findings. Outcomes for patients included in studies using CMR-confirmed criteria were favourable compared to studies with EMB-confirmed AM cases. CONCLUSION: ICD-10 codes have poor accuracy in identification of AM cases and should be used with caution in clinical research. There are important differences in management and outcomes of patients according to the selection criteria used to diagnose AM. Potential selection biases must be considered when interpreting AM cohorts and requires standardisation of inclusion criteria for AM studies.

Dysfunctional and Dysregulated Nitric Oxide Synthases in Cardiovascular Disease: Mechanisms and Therapeutic Potential.

Nitric oxide (NO) plays an important and diverse signalling role in the cardiovascular system, contributing to the regulation of vascular tone, endothelial function, myocardial function, haemostasis, and thrombosis, amongst many other roles. NO is synthesised through the nitric oxide synthase (NOS)-dependent L-arginine-NO pathway, as well as the nitrate-nitrite-NO pathway. The three isoforms of NOS, namely neuronal (NOS1), inducible (NOS2), and endothelial (NOS3), have different localisation and functions in the human body, and are consequently thought to have differing pathophysiological roles. Furthermore, as we continue to develop a deepened understanding of the different roles of NOS isoforms in disease, the possibility of therapeutically modulating NOS activity has emerged. Indeed, impaired (or dysfunctional), as well as overactive (or dysregulated) NOS activity are attractive therapeutic targets in cardiovascular disease. This review aims to describe recent advances in elucidating the physiological role of NOS isoforms within the cardiovascular system, as well as mechanisms of dysfunctional and dysregulated NOS in cardiovascular disease. We then discuss the modulation of NO and NOS activity as a target in the development of novel cardiovascular therapeutics.

MIRACLE2 Score Compared With Downtime and Current Selection Criterion for Invasive Cardiovascular Therapies After OHCA.

BACKGROUND: The MIRACLE2 score is the only risk score that does not incorporate and can be used for selection of therapies after out-of-hospital cardiac arrest (OHCA). OBJECTIVES: This study sought to compare the discrimination performance of the MIRACLE2 score, downtime, and current randomized controlled trial (RCT) recruitment criteria in predicting poor neurologic outcome after out-of-hospital cardiac arrest (OHCA). METHODS: We used the EUCAR (European Cardiac Arrest Registry), a retrospective cohort from 6 centers (May 2012-September 2022). The primary outcome was poor neurologic outcome on hospital discharge (cerebral performance category 3-5). RESULTS: A total of 1,259 patients (total downtime = 25 minutes; IQR: 15-36 minutes) were included in the study. Poor outcome occurred in 41.8% with downtime <30 minutes and in 79.3% for those with downtime >30 minutes. In a multivariable logistic regression analysis, MIRACLE2 had a stronger association with outcome (OR: 2.23; 95% CI: 1.98-2.51; P < 0.0001) than zero flow (OR: 1.07; 95% CI: 1.01-1.13; P = 0.013), low flow (OR: 1.04; 95% CI: 0.99-1.09; P = 0.054), and total downtime (OR: 0.99; 95% CI: 0.95-1.03; P = 0.52). MIRACLE2 had substantially superior discrimination for the primary endpoint (AUC: 0.877; 95% CI: 0.854-0.897) than zero flow (AUC: 0.610; 95% CI: 0.577-0.642), low flow (AUC: 0.725; 95% CI: 0.695-0.754), and total downtime (AUC: 0.732; 95% CI: 0.701-0.760). For those modeled for exclusion from study recruitment, the positive predictive value of MIRACLE2 ≥5 for poor outcome was significantly higher (0.92) than the CULPRIT-SHOCK (Culprit lesion only PCI Versus Multivessel PCI in Cardiogenic Shock) (0.80), EUROSHOCK (Testing the value of Novel Strategy and Its Cost Efficacy In Order to Improve the Poor Outcomes in Cardiogenic Shock) (0.74) and ECLS-SHOCK (Extra-corporeal life support in Cardiogenic shock) criteria (0.81) (P < 0.001). CONCLUSIONS: The MIRACLE2 score has superior prediction of outcome after OHCA than downtime and higher discrimination of poor outcome than the current RCT recruitment criteria. The potential for the MIRACLE2 score to improve the selection of OHCA patients should be evaluated formally in future RCTs.

Coronary Artery Disease in Patients with Severe Mental Illness.

Severe mental illnesses (SMI), such as schizophrenia and bipolar disorder, are associated with a decrease in life expectancy of up to two decades compared with the general population, with cardiovascular disease as the leading cause of death. SMI is associated with increased cardiovascular risk profile and early onset of incident cardiovascular disease. Following an acute coronary syndrome, patients with SMI have a worse prognosis, but are less likely to receive invasive treatment. In this narrative review, the management of coronary artery disease in patients with SMI is discussed, and avenues for future research are highlighted.

The effect of ethnicity and socioeconomic status on outcomes after resuscitated out-of-hospital cardiac arrest - Findings from a tertiary centre in South London.

Background: Out-of-hospital cardiac arrest is a common cause of morbidity and mortality, and ethnic variation in outcomes is recognised. We investigated ethnic and socioeconomic differences in arrest circumstances, rates of coronary artery disease, treatment, and outcomes in resuscitated OOHCA. Methods: Patients with resuscitated OOHCA of suspected cardiac aetiology were included in the King's Out-of-Hospital Cardiac Arrest Registry between 1-May-2012 and 31-December-2020. Results: Of 526 patients (median age 62.0 years, IQR 21.1, 74.1% male), 414 patients (78.7%) were White, 35 (6.7%) were Asian, and 77 (14.6%) were Black. Black patients had more co-existent hypertension (p = 0.007) and cardiomyopathy (p = 0.003), but less prior coronary revascularisation (p = 0.026) compared with White/Asian patients. There were no ethnic differences in location, witnesses, or bystander CPR, but Black patients had more non-shockable rhythms (p < 0.001). Black patients received less immediate coronary angiography (p < 0.001) and percutaneous coronary intervention (p < 0.001) but had lower rates of CAD (p = 0.004) than White/Asian patients. All-cause mortality at 12 months was highest amongst Black patients, followed by Asian and then White patients (57.1% vs 48.6% vs 41.3%, p = 0.032). In Black patients, excess mortality was driven by higher rates of multi-organ dysfunction but lower cardiac death than White/Asian patients, with cardiac death highest amongst Asian patients (p = 0.009). Socioeconomic status had no effect on mortality, and in a multivariable logistic regression, age, location, witnesses, and Black compared to White ethnicity were independent predictors of mortality, whilst social deprivation was not. Conclusion: In this single-centre study, Black patients had higher mortality after resuscitated OOHCA than White/Asian patients. This may be in part due to differing underlying aetiology rather than differences in arrest circumstances or social deprivation.

The Effect of a Neuronal Nitric Oxide Synthase Inhibitor on Neurovascular Regulation in Humans.

BACKGROUND: Neurovascular coupling (NVC) is a key process in cerebral blood flow regulation. NVC ensures adequate brain perfusion to changes in local metabolic demands. Neuronal nitric oxide synthase (nNOS) is suspected to be involved in NVC; however, this has not been tested in humans. Our objective was to investigate the effects of nNOS inhibition on NVC in humans. METHODS: We performed a 3-visit partially randomized, double-blinded, placebo-controlled, crossover study in 12 healthy subjects. On each visit, subjects received an intravenous infusion of either S-methyl-L-thiocitrulline (a selective nNOS-inhibitor), 0.9% saline (placebo control), or phenylephrine (pressor control). The NVC assessment involved eliciting posterior circulation hyperemia through visual stimulation while measuring posterior and middle cerebral arteries blood velocity. RESULTS: nNOS inhibition blunted the rapidity of the NVC response versus pressor control, evidenced by a reduced initial rise in mean posterior cerebral artery velocity (-3.3% [-6.5, -0.01], P=0.049), and a reduced rate of increase (ie, acceleration) in posterior cerebral artery velocity (slope reduced -4.3% [-8.5, -0.1], P=0.045). The overall magnitude of posterior cerebral artery response relative to placebo control or pressor control was not affected. Changes in BP parameters were well-matched between the S-methyl-L-thiocitrulline and pressor control arms. CONCLUSIONS: Neuronal NOS plays a role in dynamic cerebral blood flow control in healthy adults, particularly the rapidity of the NVC response to visual stimulation. This work opens the way to further investigation of the role of nNOS in conditions of impaired NVC, potentially revealing a therapeutic target.

Prognostic relevance of demographic factors in cardiac magnetic resonance-proven acute myocarditis: A cohort study.

Aim: Acute myocarditis (AM) is a heterogeneous condition with variable estimates of survival. Contemporary criteria for the diagnosis of clinically suspected AM enable non-invasive assessment, resulting in greater sensitivity and more representative cohorts. We aimed to describe the demographic characteristics and long-term outcomes of patients with AM diagnosed using non-invasive criteria. Methods and results: A total of 199 patients with cardiac magnetic resonance (CMR)-confirmed AM were included. The majority (n = 130, 65%) were male, and the average age was 39 ± 16 years. Half of the patients were White (n = 99, 52%), with the remainder from Black and Minority Ethnic (BAME) groups. The most common clinical presentation was chest pain (n = 156, 78%), with smaller numbers presenting with breathlessness (n = 25, 13%) and arrhythmias (n = 18, 9%). Patients admitted with breathlessness were sicker and more often required inotropes, steroids, and renal replacement therapy (p < 0.001, p < 0.001, and p = 0.01, respectively). Over a median follow-up of 53 (IQR 34-76) months, 11 patients (6%) experienced an adverse outcome, defined as a composite of all-cause mortality, resuscitated cardiac arrest, and appropriate implantable cardioverter defibrillator (ICD) therapy. Patients in the arrhythmia group had a worse prognosis, with a nearly sevenfold risk of adverse events [hazard ratio (HR) 6.97; 95% confidence interval (CI) 1.87-26.00, p = 0.004]. Sex and ethnicity were not significantly associated with the outcome. Conclusion: AM is highly heterogeneous with an overall favourable prognosis. Three-quarters of patients with AM present with chest pain, which is associated with a benign prognosis. AM presenting with life-threatening arrhythmias is associated with a higher risk of adverse events.

COVID-19 and the heart.

BACKGROUND: There is evidence for a bi-directional relationship between COVID-19 and the cardiovascular (CV) system. SOURCE OF DATA: Published literature. AREAS OF AGREEMENT: Pre-existing heart failure (HF) increases the risk of mortality with COVID-19. CV complications are recognized, including increased rates of acute coronary syndromes, HF, arrhythmia and myocarditis. Drugs targeting the angiotensin system are safe and may provide prognostic benefit. AREAS OF CONTROVERSY: Vaccination as a cause of myocarditis remains a key area of contention. GROWING POINTS: As the pandemic progresses, we are gaining more data about the long-term effects of COVID-19 on the CV system: long COVID, and medium-to-long-term increases in CV risk. AREAS TIMELY FOR DEVELOPING RESEARCH: Large-scale longitudinal studies will shed light on long-term CV outcomes with COVID-19. Furthermore, the differential effects of COVID-19 variants on the CV system must be investigated.

Association of cardiometabolic microRNAs with COVID-19 severity and mortality.

AIMS: Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality. METHODS AND RESULTS: We performed RNA-Seq in plasma of healthy controls (n = 11), non-severe (n = 18), and severe (n = 18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in a separate cohort of mild (n = 6), moderate (n = 39), and severe (n = 16) patients. Candidates were then measured by RT-qPCR in longitudinal samples of ICU COVID-19 patients (n = 240 samples from n = 65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality. CONCLUSION: Circulating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response.

Cholinergic imaging in dementia spectrum disorders.

The multifaceted nature of the pathology of dementia spectrum disorders has complicated their management and the development of effective treatments. This is despite the fact that they are far from uncommon, with Alzheimer's disease (AD) alone affecting 35 million people worldwide. The cholinergic system has been found to be crucially involved in cognitive function, with cholinergic dysfunction playing a pivotal role in the pathophysiology of dementia. The use of molecular imaging such as SPECT and PET for tagging targets within the cholinergic system has shown promise for elucidating key aspects of underlying pathology in dementia spectrum disorders, including AD or parkinsonian dementias. SPECT and PET studies using selective radioligands for cholinergic markers, such as [(11)C]MP4A and [(11)C]PMP PET for acetylcholinesterase (AChE), [(123)I]5IA SPECT for the α4ß2 nicotinic acetylcholine receptor and [(123)I]IBVM SPECT for the vesicular acetylcholine transporter, have been developed in an attempt to clarify those aspects of the diseases that remain unclear. This has led to a variety of findings, such as cortical AChE being significantly reduced in Parkinson's disease (PD), PD with dementia (PDD) and AD, as well as correlating with certain aspects of cognitive function such as attention and working memory. Thalamic AChE is significantly reduced in progressive supranuclear palsy (PSP) and multiple system atrophy, whilst it is not affected in PD. Some of these findings have brought about suggestions for the improvement of clinical practice, such as the use of a thalamic/cortical AChE ratio to differentiate between PD and PSP, two diseases that could overlap in terms of initial clinical presentation. Here, we review the findings from molecular imaging studies that have investigated the role of the cholinergic system in dementia spectrum disorders.

Procederes de aféresis en el Instituto de Hematología e Inmunología / Apheresis procedures at the Institute of Hematology and Immunology

Introducción: en los últimos decenios el interés por las aféresis se ha incrementado debido a que los avances tecnológicos han puesto a disposición de los profesionales de la salud equipamiento dotado de especificidad, seguridad, efectividad y rapidez para la realización de estos procederes en función de la transfusión y la terapéutica.Objetivo: presentar la experiencia acumulada en el Instituto de Hematología e Inmunología en la realización de los diferentes tipos de aféresis.Métodos: se realizó un estudio descriptivo retrospectivo que incluyó a todos los pacientes a los que se les realizó algún proceder de aféresis, en el período comprendido entre enero de 2008 y diciembre de 2013. Se analizaron las variables: datos generales del paciente, centro de procedencia, modalidad de aféresis empleada, método que se empleó y enfermedades que requirieron el proceder.Resultados: se realizaron 3 332 procederes de aféresis, 1 057 de producción con prevalencia de las tromboféresis que representó el 96,68 por ciento. De las 1 078 aféresis terapéuticas realizadas, el primer lugar correspondió a las plasmaféresis con el 26,5 por ciento, seguida de las exanguinotransfusiones (15,8 por ciento). Se realizaron, además, 1 197 aféresis de células mononucleares y plaquetas para su empleo en la Medicina Regenerativa.Conclusiones: los resultados de este primer trabajo muestran el desarrollo paulatino de las aféresis en la institución, tanto de producción como terapéutica, que por una parte promueven la producción de componentes por aféresis, lo que pone a disposición de médicos y pacientes necesitados de hemocomponentes con mayor calidad y seguridad para el tratamiento sustitutivo; y por otra, aporta información sobre las posibilidades reales de esta alternativa terapéutica para algunas enfermedades(AU)

Introduction: in recent decades, interest in apheresis has increased due to advances in technology that have made them available to health professionals with access to specific equipment, safety, effectiveness and speed to perform these procedures in terms of transfusion and therapeutics.Objective: to present the experience gained at the Institute of Hematology and Immunology in performing different types of apheresis.Methods: adescriptive retrospective study was performed which included all patients who underwent an apheresis procedure between January 2008 and December 2013. Variables were: patient´s general data, the establishment of provenance, method where analyzed apheresis was performed, method used, and diseases requiring the proceeding.Results: 3 332 apheresis proceedings were done : 1 057 for production with thrombopheresis prevalence which ranked 96,68 percen Of the 1 078 therapeutic apheresis performed, the first place went to plasmapheresis with 26,5 percen, followed by exchange transfusions (15,8 percen); 1 197 apheresis of mononuclear cells and platelets to be used in regenerative medicine were also conducted.Conclusions: the results of this preliminary study show the gradual development in the use of apheresis procedures in our institution, with both production and therapy aims, which not only allows the diffusion of production of components by apheresis which provides physicians and patients in need of blood products with higher quality and security replacement therapy, but also provides knowledge about the actual possibilities for alternative therapy in some diseases(AU)

Procederes de aféresis en el Instituto de Hematología e Inmunología / Apheresis procedures at the Institute of Hematology and Immunology

Introducción: en los últimos decenios el interés por las aféresis se ha incrementado debido a que los avances tecnológicos han puesto a disposición de los profesionales de la salud equipamiento dotado de especificidad, seguridad, efectividad y rapidez para la realización de estos procederes en función de la transfusión y la terapéutica. Objetivo: presentar la experiencia acumulada en el Instituto de Hematología e Inmunología en la realización de los diferentes tipos de aféresis. Métodos: se realizó un estudio descriptivo retrospectivo que incluyó a todos los pacientes a los que se les realizó algún proceder de aféresis, en el período comprendido entre enero de 2008 y diciembre de 2013. Se analizaron las variables: datos generales del paciente, centro de procedencia, modalidad de aféresis empleada, método que se empleó y enfermedades que requirieron el proceder. Resultados: se realizaron 3 332 procederes de aféresis, 1 057 de producción con prevalencia de las tromboféresis que representó el 96,68 por ciento. De las 1 078 aféresis terapéuticas realizadas, el primer lugar correspondió a las plasmaféresis con el 26,5 por ciento, seguida de las exanguinotransfusiones (15,8 por ciento). Se realizaron, además, 1 197 aféresis de células mononucleares y plaquetas para su empleo en la Medicina Regenerativa. Conclusiones: los resultados de este primer trabajo muestran el desarrollo paulatino de las aféresis en la institución, tanto de producción como terapéutica, que por una parte promueven la producción de componentes por aféresis, lo que pone a disposición de médicos y pacientes necesitados de hemocomponentes con mayor calidad y seguridad para el tratamiento sustitutivo; y por otra, aporta información sobre las posibilidades reales de esta alternativa terapéutica para algunas enfermedades(AU)

Introduction: in recent decades, interest in apheresis has increased due to advances in technology that have made them available to health professionals with access to specific equipment, safety, effectiveness and speed to perform these procedures in terms of transfusion and therapeutics. Objective: to present the experience gained at the Institute of Hematology and Immunology in performing different types of apheresis. Methods: adescriptive retrospective study was performed which included all patients who underwent an apheresis procedure between January 2008 and December 2013. Variables were: patient´s general data, the establishment of provenance, method where analyzed apheresis was performed, method used, and diseases requiring the proceeding. Results: 3 332 apheresis proceedings were done : 1 057 for production with thrombopheresis prevalence which ranked 96,68 percent. Of the 1 078 therapeutic apheresis performed, the first place went to plasmapheresis with 26,5 percent, followed by exchange transfusions (15,8 percent); 1 197 apheresis of mononuclear cells and platelets to be used in regenerative medicine were also conducted. Conclusions: the results of this preliminary study show the gradual development in the use of apheresis procedures in our institution, with both production and therapy aims, which not only allows the diffusion of production of components by apheresis which provides physicians and patients in need of blood products with higher quality and security replacement therapy, but also provides knowledge about the actual possibilities for alternative therapy in some diseases(AU)