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.

Treatment of Iron Deficiency in Heart Failure.

PURPOSE OF REVIEW: Heart failure (HF) is commonly associated with iron deficiency (ID), defined as insufficient levels of iron to meet physiological demands. ID's association with anaemia is well understood but it is increasingly recognised as an important comorbidity in HF, even in the absence of anaemia. This review summarises contemporary evidence for the measurement and treatment of ID, in both HFrEF and HFpEF, and specific HF aetiologies, and highlights important gaps in the evidence-base. RECENT FINDINGS: ID is common among patients with HF and associated with increased morbidity and mortality. Correcting ID in patients with HF can impact upon functional status, exercise tolerance, symptoms, and overall quality of life, irrespective of anaemia status. ID is a modifiable comorbidity in HF. Therefore, recognising and treating ID has emerging therapeutic potential and is important for all clinicians who care for patients with HF to understand the rationale and approach to treatment.

Prognostic Role of Contraindicated Drugs in Hospitalized Patients with Decompensated Heart Failure.

Due to the ageing population, patients often present to the hospital with a high burden of comorbidities and polypharmacy. For patients admitted with decompensated heart failure (HF), the evidence on the effects of contraindicated drugs on long-term mortality is scarce. Therefore, we aimed to investigate the effect of contraindicated medications on outcomes of patients admitted with decompensated HF. We analyzed all consecutive patients from the National Heart Failure Audit admitted to two tertiary centers with acutely decompensated HF between April 2020 and October 2021. We included medication classes listed as contraindicated (class III) in the most recent European and American guidelines on the management of HF. The primary outcome measure was in-hospital mortality. The secondary outcome measure was overall mortality. Overall, 716 patients admitted with acute HF were included. One-fifth (n = 156, 21.8%) were on at least one contraindicated medication at admission. The prevalence of comorbidities was comparable between medication groups. During hospitalization, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with increased in-hospital mortality (29% versus 9%, P = 0.013). On multivariable analyses, NSAID use was independently associated with worse in-hospital mortality (hazard ratio, 6.86; 95% confidence interval, 1.61-25.5; P = 0.005). However, other contraindicated medications were not associated with adverse outcomes. Postdischarge, the use of erythropoietin during admission was associated with increased mortality (54% versus 31%, P = 0.031). NSAID use is associated with increased in-hospital mortality for patients admitted with acute HF. However, inpatient use of other contraindicated medications was not associated with adverse in-hospital outcomes. Further studies are needed to confirm these results in larger and prospective cohorts. SIGNIFICANCE STATEMENT: Use of nonsteroidal anti-inflammatory drugs is associated with a worse in-hospital mortality in patients with decompensated heart failure. The prognostic role of other contraindicated medications remains still uncertain.

Cardiac imaging in rheumatic heart disease and future developments.

Rheumatic heart disease (RHD) is the most common cause of valvular heart disease worldwide, affecting millions, especially in low- and middle-income countries. Multiple imaging modalities such as cardiac CT, cardiac MRI, and three-dimensional echocardiography may be utilized in diagnosing, screening, and managing RHD. However, two-dimensional transthoracic echocardiography remains the cornerstone of imaging in RHD. Criteria developed by the World Heart Foundation in 2012 sought to unify the diagnostic imaging criteria for RHD, but concerns remain regarding their complexity and reproducibility. In the intervening years, further measures have been developed to find a balance between simplicity and accuracy. Nonetheless, there remain significant unresolved problems within imaging in RHD, including the development of a practical and sensitive screening tool to identify patients with RHD. The emergence of handheld echocardiography has the potential to revolutionize RHD management in resource-poor settings, but its role as a screening or diagnostic tool is yet to be fully established. The dramatic evolution of imaging modalities over the last few decades has not addressed RHD compared to other forms of structural heart disease. In this review, we examine the current and latest developments concerning cardiac imaging and RHD.

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.

Multi-modality imaging in transthyretin amyloid cardiomyopathy.

Transthyretin amyloid (TTR) cardiomyopathy is a disease of insidious onset, which is often accompanied by debilitating neurological and/or cardiac complications. The true prevalence is not fully known due to its elusive presentation, being often under-recognized and usually diagnosed only late in its natural history and in older patients. Because of this, effective treatment options are usually precluded by multiple comorbidities and frailty associated with such patients. Therefore, high clinical suspicion with earlier and better detection of this disease is needed. In this review, the novel applications of multimodality imaging in the diagnostic pathway of TTR cardiomyopathy are explored. These include the complimentary roles of transthoracic echocardiography, cardiac magnetic resonance, nuclear scintigraphy and positron emission tomography in quantifying cardiac dysfunction, diagnosis and risk stratification. Recent advances in novel therapeutic options for TTR have further enhanced the importance of a timely and accurate diagnosis of this disease.

Synergistic therapeutic vascular cytoprotection against complement-mediated injury induced via a PKCα-, AMPK-, and CREB-dependent pathway.

Endothelial injury and dysfunction precede accelerated arterial disease in allograft vasculopathy and systemic autoimmune diseases and involve pathogenic Abs and complement. Recent reports suggest that switching to rapamycin from calcineurin antagonists reduces posttransplant vasculopathy and prolongs survival following cardiac transplantion. The majority of these patients also receive statin therapy. We examined potential mechanisms underlying this protective response in human endothelial cells and identified synergy between rapamycin and atorvastatin. Mechanistically, atorvastatin and rapamycin activated a protein kinase Cα, AMP-activated kinase, and CREB-dependent vasculoprotective pathway, which induced decay-accelerating factor (DAF) promoter activity via binding to the cAMP response element, mutation of which attenuated promoter activity. This response significantly increased endothelial cell surface DAF and enhanced protection against complement-mediated injury. Synergy with rapamycin was reproduced by simvastatin, whereas combining atorvastatin with cyclosporine or mycophenolate in place of rapamycin was ineffective. Importantly, synergy was reproduced in vivo, in which only atorvastatin and rapamycin therapy in combination was sufficient to induce DAF on murine aortic endothelium. We believe this pathway represents an important therapeutically inducible vasculoprotective mechanism for diseases mediated by pathogenic Abs and complement, including posttransplant vasculopathy and systemic lupus erythematosus. Although our study focuses on the vascular endothelium, the findings are likely to be broadly applicable, given the diverse cellular expression of DAF.