STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) guidelines recommend pharmaco-invasive treatment if timely primary percutaneous coronary intervention (PCI) is unavailable. Full-dose tenecteplase is associated with an increased risk of intracranial hemorrhage in older patients. Whether pharmaco-invasive treatment with half-dose tenecteplase is effective and safe in older patients with STEMI is unknown. METHODS: STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) was an investigator-initiated, open-label, randomized, multicenter study. Patients ≥60 years of age with ≥2 mm ST-segment elevation in 2 contiguous leads, unable to undergo primary PCI within 1 hour, were randomly assigned (2:1) to half-dose tenecteplase followed by coronary angiography and PCI (if indicated) 6 to 24 hours after randomization, or to primary PCI. Efficacy end points of primary interest were ST resolution and the 30-day composite of death, shock, heart failure, or reinfarction. Safety assessments included stroke and nonintracranial bleeding. RESULTS: Patients were assigned to pharmaco-invasive treatment (n=401) or primary PCI (n=203). Median times from randomization to tenecteplase or sheath insertion were 10 and 81 minutes, respectively. After last angiography, 85.2% of patients undergoing pharmaco-invasive treatment and 78.4% of patients undergoing primary PCI had ≥50% resolution of ST-segment elevation; their residual median sums of ST deviations were 4.5 versus 5.5 mm, respectively. Thrombolysis In Myocardial Infarction flow grade 3 at last angiography was ≈87% in both groups. The composite clinical end point occurred in 12.8% (51/400) of patients undergoing pharmaco-invasive treatment and 13.3% (27/203) of patients undergoing primary PCI (relative risk, 0.96 [95% CI, 0.62-1.48]). Six intracranial hemorrhages occurred in the pharmaco-invasive arm (1.5%): 3 were protocol violations (excess anticoagulation in 2 and uncontrolled hypertension in 1). No intracranial bleeding occurred in the primary PCI arm. The incidence of major nonintracranial bleeding was low in both groups (<1.5%). CONCLUSIONS: Halving the dose of tenecteplase in a pharmaco-invasive strategy in this early-presenting, older STEMI population was associated with electrocardiographic changes that were at least comparable to those after primary PCI. Similar clinical efficacy and angiographic end points occurred in both treatment groups. The risk of intracranial hemorrhage was higher with half-dose tenecteplase than with primary PCI. If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02777580.

Depression, anxiety, and quality of life as predictors of rehospitalization in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a severe condition, often co-occurring with depression and anxiety, that strongly affects the quality of life (QoL) in some patients. Conversely, depressive and anxiety symptoms are associated with a 2-3 fold increase in mortality risk and were shown to act independently of typical risk factors in CHF progression. The aim of this study was to examine the impact of depression, anxiety, and QoL on the occurrence of rehospitalization within one year after discharge in CHF patients. METHODS: 148 CHF patients were enrolled in a 10-center, prospective, observational study. All patients completed two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Questionnaire Short Form Health Survey 36 (SF-36) at discharge timepoint. RESULTS: It was found that demographic and clinical characteristics are not associated with rehospitalization. Still, the levels of depression correlated with gender (p ≤ 0.027) and marital status (p ≤ 0.001), while the anxiety values ​​were dependent on the occurrence of chronic obstructive pulmonary disease (COPD). However, levels of depression (HADS-Depression) and anxiety (HADS-Anxiety) did not correlate with the risk of rehospitalization. Univariate logistic regression analysis results showed that rehospitalized patients had significantly lower levels of Bodily pain (BP, p = 0.014), Vitality (VT, p = 0.005), Social Functioning (SF, p = 0.007), and General Health (GH, p = 0.002). In the multivariate model, poor GH (OR 0.966, p = 0.005) remained a significant risk factor for rehospitalization, and poor General Health is singled out as the most reliable prognostic parameter for rehospitalization (AUC = 0.665, P = 0.002). CONCLUSION: Taken together, our results suggest that QoL assessment complements clinical prognostic markers to identify CHF patients at high risk for adverse events. CLINICAL TRIAL REGISTRATION: The study is registered under http://clinicaltrials.gov (NCT01501981, first posted on 30/12/2011), sponsored by Charité - Universitätsmedizin Berlin.

Alirocumab after acute coronary syndrome in patients with a history of heart failure.

AIMS: Patients with heart failure (HF) have not been shown to benefit from statins. In a post hoc analysis, we evaluated outcomes in ODYSSEY OUTCOMES in patients with vs. without a history of HF randomized to the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab or placebo. METHODS AND RESULTS: Among 18 924 patients with recent acute coronary syndrome (ACS) receiving intensive or maximum-tolerated statin treatment, the primary outcome of major adverse cardiovascular events (MACE) was compared in patients with or without a history of HF. The pre-specified secondary outcome of hospitalization for HF was also analysed. Overall, 2815 (14.9%) patients had a history of HF. Alirocumab reduced low-density lipoprotein cholesterol and lipoprotein(a) similarly in patients with or without HF. Overall, alirocumab reduced MACE compared with placebo [hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.78-0.93; P = 0.0001]. This effect was observed among patients without a history of HF (HR: 0.78; 95% CI: 0.70-0.86; P < 0.0001), but not in those with a history of HF (HR: 1.17; 95% CI: 0.97-1.40; P = 0.10) (Pinteraction = 0.0001). Alirocumab did not reduce hospitalization for HF, overall or in patients with or without prior HF. CONCLUSION: Alirocumab reduced MACE in patients without a history of HF but not in patients with a history of HF. Alirocumab did not reduce hospitalizations for HF in either group. Patients with a history of HF are a high-risk group that does not appear to benefit from PCSK9 inhibition after ACS.

Heart Failure Association, Heart Failure Society of America, and Japanese Heart Failure Society Position Statement on Endomyocardial Biopsy.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumors. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples has significantly improved the diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (1) an overview of the practical approach to EMB, (2) an update on indications for EMB, (3) a revised plan for heart transplant rejection surveillance, (4) the impact of multimodality imaging on EMB, and (5) the current clinical practice in the worldwide use of EMB.

Heart failure care in the Central and Eastern Europe and Baltic region: status, barriers, and routes to improvement.

Despite improvements over recent years, morbidity and mortality associated with heart failure (HF) are higher in countries in the Central and Eastern Europe and Baltic region than in Western Europe. With the goal of improving the standard of HF care and patient outcomes in the Central and Eastern Europe and Baltic region, this review aimed to identify the main barriers to optimal HF care and potential areas for improvement. This information was used to suggest methods to improve HF management and decrease the burden of HF in the region that can be implemented at the national and regional levels. We performed a literature search to collect information about HF epidemiology in 11 countries in the region (Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Serbia, and Slovenia). The prevalence of HF in the region was 1.6-4.7%, and incidence was 3.1-6.0 per 1000 person-years. Owing to the scarcity of published data on HF management in these countries, we also collected insights on local HF care and management practices via two surveys of 11 HF experts representing the 11 countries. Based on the combined results of the literature review and surveys, we created national HF care and management profiles for each country and developed a common patient pathway for HF for the region. We identified five main barriers to optimal HF care: (i) lack of epidemiological data, (ii) low awareness of HF, (iii) lack of national HF strategies, (iv) infrastructure and system gaps, and (v) poor access to novel HF treatments. To overcome these barriers, we propose the following routes to improvement: (i) establish regional and national prospective HF registries for the systematic collection of epidemiological data; (ii) establish education campaigns for the public, patients, caregivers, and healthcare professionals; (iii) establish formal HF strategies to set clear and measurable policy goals and support budget planning; (iv) improve access to quality-of-care centres, multidisciplinary care teams, diagnostic tests, and telemedicine/telemonitoring; and (v) establish national treatment monitoring programmes to develop policies that ensure that adequate proportions of healthcare budgets are reserved for novel therapies. These routes to improvement represent a first step towards improving outcomes in patients with HF in the Central and Eastern Europe and Baltic region by decreasing disparities in HF care within the region and between the region and Western Europe.

Rationale and design of the COlchicine for Prevention of the Post-pericardiotomy Syndrome and Post-operative Atrial Fibrillation (COPPS-2 trial): a randomized, placebo-controlled, multicenter study on the use of colchicine for the primary prevention of the postpericardiotomy syndrome, postoperative effusions, and postoperative atrial fibrillation.

BACKGROUND: The efficacy and safety of colchicine for the primary prevention of the postpericardiotomy syndrome (PPS), postoperative effusions, and postoperative atrial fibrillation (POAF) remain uncertain. Although preliminary data from a single trial of colchicine given for 1 month postoperatively (COPPS trial) were promising, the results have not been confirmed in a large, multicenter trial. Moreover, in the COPPS trial, colchicine was given 3 days postoperatively. METHODS: The COPPS-2 study is a multicenter, double-blind, placebo-controlled randomized trial. Forty-eight to 72 hours before planned cardiac surgery, 360 patients, 180 in each treatment arm, will be randomized to receive placebo or colchicine without a loading dose (0.5 mg twice a day for 1 month in patients weighing ≥70 kg and 0.5 mg once for patients weighing <70 kg or intolerant to the highest dose). The primary efficacy end point is the incidence of PPS, postoperative effusions, and POAF at 3 months after surgery. Secondary end points are the incidence of cardiac tamponade or need for pericardiocentesis or thoracentesis, PPS recurrence, disease-related admissions, stroke, and overall mortality. CONCLUSIONS: The COPPS-2 trial will evaluate the use of colchicine for the primary prevention of PPS, postoperative effusions, and POAF, potentially providing stronger evidence to support the use of preoperative colchicine without a loading dose to prevent several postoperative complications. ClinicalTrials.gov Identifier: NCT01552187.

Epicardial halo phenomenon: a guide for pericardiocentesis?

The epicardial halo delineates the heart shadow in fluoroscopy. To establish whether the sign is applicable to pericardiocentesis guidance, three investigators evaluated its intensity as absent = grade 0, indistinct = 0.5, clear = 1, intensive = 2 in posterior-anterior (PA) and lateral fluoroscopies recorded before pericardiocentesis or cardiac catheterization (Philips Integris-II BH3000). Three populations were studied: (a) 32 patients with pericardial effusion (PE group), 53.1 % males, aged 53.9 ± 13.9 years; (b) 14 patients with perimyocarditis (PM group), 64.3 % males, aged 51.6 ± 14.4 years; and (c) 46 coronary patients (CAD group), no PE, 95.6 % males, aged 67.3 ± 11.8 years. The intensity of the halo phenomenon was highest in patients with PE, lowest in patients with CAD, and intermediate in patients with PM (median sum of grades in PA/lateral view: 4/5 vs. 2/2.5 vs. 3/3, respectively) (p < 0.01). The halo phenomenon correlated well with HR and echocardiographic PE size in both angiographic views. The correlation with body mass index (BMI) and age was significant only in the lateral view and with PE volume only in the PA view. The sensitivity of the halo sign for PE was 84.1 % in PA and 92.0 % in lateral views. In 10/32 PE patients, the evaluation of the sign was repeated after PE drainage, revealing lower grades both in PA and in lateral views (p < 0.01). In conclusion, the epicardial halo sign is highly sensitive for the detection of a PE; it correlates well in at least one angiographic projection with the PE volume, HR, age, BMI, and the PE size in echocardiography and could be therefore applied as a safety guide for pericardiocentesis.

Pericardial cytokines in neoplastic, autoreactive, and viral pericarditis.

Pericardial cytokine patterns in various diseases are not well established. We have analyzed pericardial proinflammatory (interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha) and immunoregulatory cytokines (transforming growth factor (TGF)-beta1 and interferon (IFN)-gamma) in patients with pericarditis, myocarditis, and ischemic heart disease. Pericardial fluid was obtained in 30 subsequent patients undergoing pericardiocentesis (Group 1: 60 % males, 52.4 ± 14.2 years) and in 21 patients during aortocoronary bypass surgery (Group 2: 42.9 % males, age 67.2 ± 7.4 years). After clinical, laboratory, echocardiography examination, fiberoptic pericardioscopy (Storz-AF1101Bl, Germany) and pericardial/epicardial biopsy Group 1 was subdivided to 40 % neoplastic, 36.6 % autoreactive, 10 % iatrogenic, and 13.3 % viral pericarditis. Samples were promptly aliquoted, frozen, and stored at -70 °C. The cytokines were estimated using quantikine enzyme amplified-sensitivity immuno-assays (R&D Systems, USA) and the results compared between neoplastic, viral, iatrogenic, and autoreactive pericarditis and surgical groups. IL-6 was significantly increased in PE versus serum in all forms of pericarditis (except in autoreactive) and increased in comparison with pericardial fluid of surgical patients. TNF-alpha was increased only in PE of patients with viral pericarditis in comparison with Group 2. TGF-beta1 was strikingly lower in the PE than in the serum of all pericarditis patients. However, TGF-beta1 levels in PE were significantly higher in Group 1 than in Group 2, except in viral pericarditis. IFN-gamma levels did not significantly differ between PE and serum or in comparison with Group 2. The cytokine pattern "high TNF-alpha/low TGF-beta1" was found in viral pericarditis and low IL-6 in autoreactive PE. Different etiologies of pericardial inflammation did not influence the IFN-gamma levels. IL-6 pericardial to serum ratio was significantly higher in autoreactive PE than in viral and neoplastic forms. However, TNF-alpha and IFN-gamma pericardial to serum ratios were significantly higher in viral than in autoreactive and neoplastic PE.

Pericardial syndromes: an update after the ESC guidelines 2004.

Despite a myriad of causes, pericardial diseases present in few clinical syndromes. Acute pericarditis should be differentiated from aortic dissection, myocardial infarction, pneumonia/pleuritis, pulmonary embolism, pneumothorax, costochondritis, gastroesophageal reflux/neoplasm, and herpes zoster. High-risk features indicating hospitalization are: fever >38 °C, subacute onset, large effusion/tamponade, failure of non-steroidal anti-inflammatory drugs (NSAIDs), previous immunosuppression, trauma, anticoagulation, neoplasm, and myopericarditis. Treatment comprises 10-14-days NSAID plus 3 months colchicine (2 × 0.5 mg; 1 × 0.5 mg in patients <70 kg). Corticosteroids are avoided, except for autoimmunity, as they facilitate the recurrences. Echo-guided pericardiocentesis (±fluoroscopy) is indicated for tamponade and effusions >2 cm. Smaller effusions are drained if neoplastic, purulent or tuberculous etiology is suspected. In recurrent pericarditis, repeated testing for autoimmune and thyroid disease is appropriate. Pericardioscopy and pericardial/epicardial biopsy may clarify the etiology. Familial clustering was recently associated with tumor necrosis factor receptor-associated periodic syndrome (TNFRSF1A gene mutation). Treatment includes 10-14 days NSAIDs with colchicine 0.5 mg bid for up to 6 months. In non-responders, low-dose steroids, intrapericardial steroids, azathioprine, and cyclophosphamide can be tried. Successful management with interleukin-1 receptor antagonist (anakinra) was recently reported. Pericardiectomy remains the last option in >2 years severely symptomatic patients. In constriction, expansion of the heart is impaired by the rigid, chronically inflamed/thickened pericardium (no thickening ~20 %). Chest radiography, echocardiography, computerized tomography, magnetic resonance imaging, hemodynamics, and endomyocardial biopsy indicate the diagnosis. Pericardiectomy is the only treatment for permanent constriction. Predictors of poor survival are prior radiation, renal dysfunction, high pulmonary artery pressures, poor left ventricular function, hyponatremia, age, and simultaneous HIV and tuberculous infection.

Cardiac tamponade.

Cardiac tamponade is a medical emergency caused by the progressive accumulation of pericardial fluid (effusion), blood, pus or air in the pericardium, compressing the heart chambers and leading to haemodynamic compromise, circulatory shock, cardiac arrest and death. Pericardial diseases of any aetiology as well as complications of interventional and surgical procedures or chest trauma can cause cardiac tamponade. Tamponade can be precipitated in patients with pericardial effusion by dehydration or exposure to certain medications, particularly vasodilators or intravenous diuretics. Key clinical findings in patients with cardiac tamponade are hypotension, increased jugular venous pressure and distant heart sounds (Beck triad). Dyspnoea can progress to orthopnoea (with no rales on lung auscultation) accompanied by weakness, fatigue, tachycardia and oliguria. In tamponade caused by acute pericarditis, the patient can experience fever and typical chest pain increasing on inspiration and radiating to the trapezius ridge. Generally, cardiac tamponade is a clinical diagnosis that can be confirmed using various imaging modalities, principally echocardiography. Cardiac tamponade is preferably resolved by echocardiography-guided pericardiocentesis. In patients who have recently undergone cardiac surgery and in those with neoplastic infiltration, effusive-constrictive pericarditis, or loculated effusions, fluoroscopic guidance can increase the feasibility and safety of the procedure. Surgical management is indicated in patients with aortic dissection, chest trauma, bleeding or purulent infection that cannot be controlled percutaneously. After pericardiocentesis or pericardiotomy, NSAIDs and colchicine can be considered to prevent recurrence and effusive-constrictive pericarditis.

Impact analysis of heart failure across European countries: an ESC-HFA position paper.

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC-HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs-in terms of quality of life-in European countries.

Cardiac remodelling - Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology.

In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting.

Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology.

Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.

Impact of disease activity on impaired glucose metabolism in patients with rheumatoid arthritis.

OBJECTIVE: To explore glucose metabolism in rheumatoid arthritis (RA) and its association with insulin resistance (IR) risk factors and disease activity indicators, including matrix metalloproteinase-3 (MMP3). METHODS: This single-center study included 127 non-diabetic subjects: 90 RA patients and 37 matched controls. IR-related risk factors, disease activity (DAS28-ESR/CRP), concentrations of inflammation markers, MMP3, glucose, specific insulin, and C-peptide (a marker of ß-cell secretion) were determined. Homeostasis Model Assessment was used to establish insulin resistance (HOMA2-IR) and sensitivity (HOMA2-%S). Associations of HOMA2 indices with IR-related risk factors, inflammation markers, and RA activity were tested using multiple regression analyses. RESULTS: RA patients had significantly increased HOMA2-IR index than controls. In the RA group, multivariate analysis revealed DAS28-ESR, DAS28-CRP, tender joint counts, patient's global assessment, and MMP3 level as significant positive predictors for HOMA2-IR (ß = 0.206, P = 0.014; ß = 0.192, P = 0.009; ß = 0.121, P = 0.005; ß = 0.148, P = 0.007; ß = 0.075, P = 0.025, respectively), and reciprocal negative for HOMA2-%S index. According to the value of the coefficient of determination (R2), DAS28-ESR ≥ 5.1 has the largest proportion of variation in both HOMA2-IR indices. DAS28-ESR ≥ 5.1 and ESR were independent predictors for increased C-peptide concentration (ß = 0.090, P = 0.022; ß = 0.133, P = 0.022). Despite comparability regarding all IR-related risk factors, patients with DAS28-ESR ≥ 5.1 had higher HOMA2-IR than controls [1.7 (1.2-2.5) vs. 1.2 (0.8-1.4), P = 0.000]. There was no difference between patients with DAS28-ESR < 5.1 and controls [1.3 (0.9-1.9) vs. 1.2 (0.8-1.4), P = 0.375]. CONCLUSIONS: RA activity is an independent risk factor for impaired glucose metabolism. DAS28-ESR ≥ 5.1 was the main contributor to this metabolic disturbance, followed by MMP3 concentration, outweighing the impact of classic IR-related risk factors.

Positron emission tomography in clinically suspected myocarditis - STREAM study design.

AIM: Myocarditis is an inflammatory disease associated with increased glucose uptake. The hypothesis of this study assumes that 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) may improve specificity and sensitivity in the diagnosis of myocarditis and referral for endomyocardial biopsy (EMB), adding additional information for post-discharge risk stratification. The aim of the study is to assess the diagnostic and prognostic feasibility of FDG-PET/CT in comparison to cardiac magnetic resonance (CMR) (alone or in combination) in patients with clinically suspected myocarditis undergoing EMB. METHODS: Fifty hospitalized patients with clinically suspected myocarditis who meet the inclusion/exclusion criteria will be enrolled in a prospective, observational, multicentre, cohort study (NCT04085718). The primary endpoint is the sensitivity and specificity of FDG-PET/CT imaging in the diagnosis of myocarditis. The main secondary endpoints include correlation of FDG-PET/CT imaging with CMR, echocardiography, and EMB results. The patients will undergo the following evaluations: clinical examination, blood tests (including biomarkers of fibrosis and anti-heart autoantibodies (AHA)), ECG, 24 h Holter ECG, echocardiography, CMR, as well as resting single photon emission computed tomography (SPECT) to assess possible myocardial perfusion defects, cardiac FDG-PET/CT and right ventricular EMB. After 6-months a follow-up visit will be performed (including 24 h Holter ECG, echocardiography and CMR). Investigators evaluating individual studies (CMR, SPECT, FDG-PET/CT and EMB) are to be blinded to the other tests' results. CONCLUSION: We believe that FDG-PET/CT alone or in combination with CMR may be a useful tool for improving diagnostic accuracy in patients with clinically suspected myocarditis.

Navigating between Scylla and Charybdis: challenges and strategies for implementing guideline-directed medical therapy in heart failure with reduced ejection fraction.

Guideline-directed medical therapy (GDMT) has the potential to reduce the risks of mortality and hospitalisation in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, real-world data indicate that many patients with HFrEF do not receive optimised GDMT, which involves several different medications, many of which require up-titration to target doses. There are many challenges to implementing GDMT, the most important being patient-related factors (comorbidities, advanced age, frailty, cognitive impairment, poor adherence, low socioeconomic status), treatment-related factors (intolerance, side-effects) and healthcare-related factors that influence availability and accessibility of HF care. Accordingly, international disparities in resources for HF management and limited public reimbursement of GDMT, coupled with clinical inertia for treatment intensification combine to hinder efforts to provide GDMT. In this review paper, authors aim to provide solutions based on available evidence, practical experience, and expert consensus on how to utilise evolving strategies, novel medications, and patient profiling to allow the more comprehensive uptake of GDMT. Authors discuss professional education, motivation, and training, as well as patient empowerment for self-care as important tools to overcome clinical inertia and boost GDMT implementation. We provide evidence on how multidisciplinary care and institutional accreditation can be successfully used to increase prescription rates and adherence to GDMT. We consider the role of modern technologies in advancing professional and patient education and facilitating patient-provider communication. Finally, authors emphasise the role of novel drugs (especially sodium-glucose co-transporter 2 inhibitors), and a tailored approach to drug management as evolving strategies for the more successful implementation of GDMT.

Heart Failure Association of the ESC, Heart Failure Society of America and Japanese Heart Failure Society Position statement on endomyocardial biopsy.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB.