Clinical and Pathophysiologic Insights of Free triiodothyronine/Free thyroxine Ratio in Patients with Heart Failure with Preserved Ejection Fraction: Data from the NETDiamond Cohort.

BACKGROUND: Thyroid dysfunction is common in patients with heart failure (HF). Impaired conversion of free T4 (FT4) into free T3 (FT3) is thought to occur in these patients, decreasing the availability of FT3 and contributing to HF progression. In HF with preserved ejection fraction (HFpEF), it is not known whether changes in conversion of thyroid hormones (THs) are associated with clinical status and outcomes. OBJECTIVES: The objective of this study was to evaluate the association of FT3/FT4 ratio and TH with clinical, analytical, and echocardiographic parameters, as well as their prognostic impact in individuals with stable HFpEF. METHODS: We evaluated 74 HFpEF participants of the NETDiamond cohort without known thyroid disease. We performed regression modeling to study the associations of TH and FT3/FT4 ratio with clinical, anthropometric, analytical, and echocardiographic parameters, and survival analysis to evaluate associations with the composite of diuretic intensification, urgent HF visit, HF hospitalization, or cardiovascular death over a median follow-up of 2.8 years. RESULTS: The mean age was 73.7 years and 62% were men. The mean FT3/FT4 ratio was 2.63 (standard deviation: 0.43). Subjects with lower FT3/FT4 ratio were more likely to be obese and have atrial fibrillation. Lower FT3/FT4 ratio was associated with higher body fat (ß = -5.60 kg per FT3/FT4 unit, p = 0.034), higher pulmonary arterial systolic pressure (PASP) (ß = -10.26 mm Hg per FT3/FT4 unit, p = 0.002), and lower left ventricular ejection fraction (LVEF) (ß = 3.60% per FT3/FT4 unit, p = 0.008). Lower FT3/FT4 ratio was associated with higher risk for the composite HF outcome (HR = 2.50, 95% CI: 1.04-5.88, per 1-unit decrease in FT3/FT4, p = 0.041). CONCLUSIONS: In patients with HFpEF, lower FT3/FT4 ratio was associated with higher body fat, higher PASP, and lower LVEF. Lower FT3/FT4 predicted a higher risk of diuretic intensification, urgent HF visits, HF hospitalization, or cardiovascular death. These findings suggest that decreased FT4 to FT3 conversion might be a mechanism associated with HFpEF progression.

Lung and Pleural Immunoglobulin G4-Related Disease: Two Contrasting Case Reports.

Immunoglobulin G4-related disease (IgG4-RD) is an immunomediated disease that can virtually affect any organ. Despite the pancreas being known as the most frequently involved organ, pulmonary and pleural IgG4-RD is being increasingly reported. The authors present two cases of IgG4-RD diagnosed in the same year, with different presentations and outcomes, in which the lung and pleural involvement were essential for the diagnosis. Recognizing IgG4-RD as a possible cause of chronic pleural effusion and/or thickening and lung abnormalities is important for an early diagnosis and prognosis improvement.

Mitral annular disjunction: Beyond mitral valve prolapse.

Mitral annular disjunction (MAD) is an easily identifiable entity on transthoracic echocardiography, but is still poorly recognized or ignored. It is often associated with mitral valve prolapse and is itself a risk marker for ventricular arrhythmias and sudden cardiac death, but the management and risk stratification of these patients is not systematized. Two clinical cases of MAD associated with mitral valve prolapse and ventricular arrhythmias are presented. The first case is of a patient with a history of surgical intervention on the mitral valve due to Barlow's disease. He presented to the emergency department with sustained monomorphic ventricular tachycardia requiring emergent electrical cardioversion. MAD with transmural fibrosis at the level of the inferolateral wall was documented. The second report is of a young woman with palpitations and frequent premature ventricular contractions on Holter with documentation of valvular prolapse and MAD, and focuses on the risk stratification approach. The present article offers a review of the literature regarding the arrhythmic risk of MAD and mitral valve prolapse, as well as a review of risk stratification in these patients.

Left ventricular noncompaction associated with a pathogenic mutation in the MYH7 gene: Known mutation, different phenotype.

Left ventricular noncompaction (LVNC) is a genetically heterogeneous cardiomyopathy, with familial and sporadic forms, but genetic testing only identifies a pathogenic mutation in a minority of cases. The main complications are heart failure, embolism and dysrhythmias. Herein we report a familial case of LVNC associated with a mutation in the MYH7 gene and review the literature regarding controversies in LVNC. A 50-year-old woman was referred to the cardiology clinic for palpitations. She underwent echocardiography and cardiac magnetic resonance imaging that revealed mild left ventricular systolic dysfunction and LVNC criteria. She had several episodes of non-sustained ventricular tachycardia and received an implantable cardioverter-defibrillator (ICD). Genetic testing revealed the c.1003G>C (p.Ala335Pro) mutation in the MYH7 gene. Familial screening showed clear genotype-phenotype cosegregation, which provided strong evidence for the pathogenic role of this mutation. To the best of our knowledge, this is the first report of LVNC associated with the p.Ala335Pro mutation in the MYH7 gene. This mutation has been described in hypertrophic cardiomyopathy, suggesting that the same pathogenic sarcomere mutation may be associated with different cardiomyopathies. This case also highlights the current difficulties regarding decisions on ICD implantation for primary prevention of sudden cardiac death in LVNC.

Relaxin-2, pathophysiological insights and outcomes in heart failure with preserved ejection fraction: Findings from the NETDiamond cohort.

AIMS: The role of relaxin-2 as a circulating marker in heart failure (HF) with preserved ejection fraction (HFpEF) is poorly understood. We aimed to characterize relaxin-2 circulating levels in a population of chronic HFpEF patients and their association with long-term prognosis. METHODS: Relaxin-2 serum levels were measured in 85 chronic HFpEF patients from a prospective cohort study (NETDiamond). Clinical, imaging, and analytical data were compared across relaxin-2 tertiles. The primary outcome was a composite of cardiovascular death, HF hospitalisation, acute HF episode or diuretic intensification and the secondary outcome a composite of cardiovascular death and total HF hospitalisations. Cox regression and negative binomial models were used to assess the relation between relaxin-2 and the outcomes. RESULTS: Relaxin-2 levels were positively associated with left atrial volume, left ventricular mass and peripheral oedema, and negatively associated with ischemic heart disease and statin use. Higher relaxin-2 levels were associated with an increased risk of primary outcome, even after adjustment for age, B-type natriuretic peptide (BNP) and glomerular filtration rate (eGFR) (adjusted HR = 2.80, 95%CI 1.4-7.3, p = 0.034 for tertile 3). They were also associated with the occurrence of the secondary outcome (Incidence Rate Ratio = 5.28, 95%CI 1.2-23.2, p = 0.027), but this significance was lost when simultaneously adjusted for BNP and eGFR. CONCLUSION: In chronic HFpEF patients, higher relaxin-2 circulating levels were associated with left chambers remodelling, congestion, and adverse prognosis. These findings support a potential role for relaxin-2 as a pathophysiological agent and as a circulating biomarker in HFpEF.

Optimizing prognosis in atrial fibrillation: A call to action in Portugal.

Atrial fibrillation (AF), the most common arrhythmia in the adult population worldwide, represents a significant burden in terms of cardiovascular mortality and morbidity and has repercussions on health economics. Oral anticoagulation (OAC) is key to stroke prevention in AF and, in recent years, results from landmark clinical trials of non-vitamin K oral anticoagulants (NOAC) have triggered a paradigm shift in thrombocardiology. Despite these advances, there is still a significant residual vascular risk associated with silent AF, bleeding, premature sudden death and heart failure. The authors review AF epidemiologic data, the importance of new tools for early AF detection, the current role of catheter ablation for rhythm control in AF, the state-of-the-art in periprocedural OAC, the optimal management of major bleeding, the causes of residual premature death and future strategies for improvements in AF prognosis.

Perimyocarditis Following COVID-19 Vaccination.

A 39-year-old male was admitted in the emergency room with chest pain. He had been given the second dose of Pfizer-BioNTech COVID-19 vaccine 3 days before. The patient denied taking any other medication beyond the usual. He didn't feel sick in the previous days/weeks. Laboratory studies revealed elevated serum levels of troponin and C-reactive protein. An autoantibody screen and a serologic panel to detect common viruses were negative. A cardiac MRI showed myocardial edema/inflammation and confirmed the diagnosis of perimyocarditis which was considered to be a consequence of COVID-19 vaccination. Physicians should be aware of the possibility of cardiovascular complications after COVID-19 vaccination.

Brugada syndrome: Eligibility for subcutaneous implantable cardioverter-defibrillator after exercise stress test.

INTRODUCTION: Brugada syndrome (BrS) is a channelopathy associated with ventricular arrhythmias and sudden cardiac death. In patients at high risk of sudden death, an implantable cardioverter-defibrillator is indicated. Subcutaneous implantable cardioverter-defibrillators (S-ICDs) are an alternative to transvenous systems, with reduced risk of infection and complications associated with system extraction or explantation. OBJECTIVE: To test electrocardiographic eligibility for S-ICD placement after exercise stress testing (EST) in patients with BrS. METHODS: The sample included 35 consecutive patients with BrS. Electrocardiographic eligibility was assessed using the Boston Scientific model 2889 EMBLEM™ S-ICD automated screening tool, in four phases: decubitus and orthostatism, and before and after EST. Those who had at least one acceptable vector in the four measurements were considered eligible. RESULTS: In this study, 71.4% of patients were male and mean age was 53.86±12 years. In screening prior to EST, 14.3% of patients (n=5) were not eligible for an S-ICD. There was a statistically significant association between ineligibility and presence of complete right bundle branch block and history of syncope. After EST, 16.7% of initially eligible patients no longer had eligible vectors (n=5). CONCLUSION: In this study, 16.7% of patients previously eligible for an S-ICD were no longer eligible after EST. This result demonstrates the importance of screening after EST in all patients with BrS and with indication for an S-ICD, and may influence decisions concerning which ICD to implant or whether to institute pharmacological measures that avoid inappropriate therapies.

A state of the art review on the novel mediator asprosin in the metabolic syndrome.

Metabolic syndrome is a complex and heterogeneous pathology characterized by a cluster of biochemical, clinical, and metabolic factors that came together in raising the risk of cardiovascular diseases, type 2 diabetes mellitus, and all-cause mortality. Some of these features are well defined in this syndrome like: obesity, inflammation, hypertension, insulin resistance, atherosclerotic dyslipidemias, endothelial dysfunction, and inflammation. This circuit is intermediated by a complex network of hormones, cytokines, transcription factors, and adipokines, among others. Some like leptin, adiponectin, Plasminogen activator inhibitor-1, interleukin-6, Tumor necrosis factor, and their influence on the metabolic syndrome are well described in the literature and new players are described continuously. One novel player was described in 2016 by Romere et al as a fasting-induced glycogenic protein hormone named asprosin. In order to perform a state-of-the-art, nonsystematic review of asprosin, a study of the available literature was carried out in the main database (Pubmed) and the results were studied and correlated to better understand the mechanism of action of this hormone. Asprosin is not only associated with the metabolic syndrome features like glucose and lipid metabolism, insulin resistance, obesity and inflammation but also in other pathologies metabolic syndrome related like diabetic retinopathy, polycystic ovary syndrome and anorexia nervosa. A limited number of pathways were already unveiled although much more research is needed to better understand the therapeutical potential of asprosin in the metabolic syndrome.

Cardiac Angiosarcoma: From Cardiac Tamponade to Ischaemic Stroke - A Diagnostic Challenge.

Cardiac angiosarcoma (CA) is the most common primary malignant heart tumour. Its atypical symptoms and rapidly progressive nature contribute to delayed diagnosis and poor outcome. We report the case of a 52-year-old woman admitted with a large pericardial effusion. An extensive study of the aetiology of the pericardial effusion was inconclusive. Two months later the patient returned with ischaemic stroke. An echocardiogram revealed a probable right atrium contained rupture. The patient was submitted to surgical correction but died 9 days later. Histology revealed an angiosarcoma. This case exemplifies the atypical presentation of CA and highlights the importance of a multimodal diagnostic work-up in patients with idiopathic pericardial effusion. LEARNING POINTS: Cardiac angiosarcoma is often overlooked as an initial diagnosis because of its rarity and atypical symptoms, which, in association with its aggressiveness, contribute to delayed diagnosis and fatal outcome.Pericardial biopsy is an important technique that may help to disclose the aetiology of pericardial effusion and should be considered for the confirmation of malignant pericardial disease.Patients presenting with pericardial effusion with cardiac tamponade with an unclear cause after diagnostic work-up should be followed closely.

Attenuation of the cardiovascular and metabolic complications of obesity in CD14 knockout mice.

AIMS: Although toll-like receptors (TLR) are known to mediate the metabolic complications of obesity, the mechanisms underlying its activation remain largely unknown. The present study analyzed a model of diet-induced obesity in mice lacking the TLR4/TLR2 co-receptor CD14. MAIN METHODS: Six-week-old male mice lacking CD14 (n = 16) were allocated to either a control diet or a high-fat high-simple carbohydrate diet (5.4 kcal/g; 35% fat; 35% sucrose), and compared with C57BL/6 (WT; n = 15) controls. After 12 weeks, body composition, basal sympathetic activity, non-invasive blood pressure and glucose tolerance were evaluated. Hepatic and adipose tissues were collected for mRNA quantification, histology and LPS incubation. KEY FINDINGS: In both WT and CD14 knockout mice, obesity was accompanied by TLR2 and TLR4 upregulation. However, obese mice lacking CD14 presented decreased lipid and macrophage content in hepatic and adipose tissues, lower urinary levels of noradrenaline, decreased systolic blood pressure, reduced fasting plasma glucose and blunted glucose intolerance, compared with obese WT group. In the presence of exogenous sCD14, adipose tissue incubation with LPS-induced TLR2 and TNF-alpha upregulation in both WT and CD14 knockout obese mice. SIGNIFICANCE: In our model of diet-induced obesity, mice lacking CD14 showed lower adiposity and hepatic steatosis, improved glucose homeostasis, blunted sympathetic overactivity and reduced blood pressure elevation. This was observed in the presence of preserved TLR4 and TLR2 gene expression, and intact TLR4 signaling pathways. These results suggest that CD14-mediated TLR activation might contribute to the cardiovascular and metabolic complications of obesity.

Standardization of laboratory and lipid profile evaluation: A call for action with a special focus in 2016 ESC/EAS dyslipidaemia guidelines - Full report.

Even with the improvement in lifestyle interventions, a better control of cardiovascular (CV) risk factors, and improvements in CV outcomes, cardiovascular disease (CVD) still persists as the leading cause of morbidity and mortality in Portugal and Europe. Atherogenic dyslipidaemias, namely hypercholesterolaemia, have a crucial and causal role in the development of atherosclerotic CVD. The clinical approach of a patient with dyslipidaemia involves a watchful diagnosis, sustained in lipid and lipoprotein laboratory procedures, which must be harmonized and standardized. Standardization of lipid test results and reports, incorporating the total CV risk and the respective target and goals of treatment approach, guarantees that clinical guidelines and good clinical practices are followed and respected, increasing the reliability of lipid disorders screening, producing more accurate diagnoses and CV risk stratification, and improving the CV prevention and the achievement the desirable treatment goals.

Standardization of laboratory lipid profile assessment: A call for action with a special focus on the 2016 ESC/EAS dyslipidemia guidelines - Executive summary: A consensus endorsed by the Cardiovascular Risk and Prevention Group of the Portuguese Internal Medicine Society, the Portuguese Atherosclerosis Society, the Portuguese Society of Cardiology, the Portuguese Society of Laboratory Medicine, and the Portuguese Association of Clinical Chemistry.

Even with improvements in lifestyle interventions, better control of cardiovascular (CV) risk factors, and improvements in CV outcomes, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in Portugal and Europe. Atherogenic dyslipidemias, particularly hypercholesterolemia, have a crucial causal role in the development of atherosclerotic CVD. The clinical approach to a patient with dyslipidemia requires an accurate diagnosis, based on harmonized and standardized lipid and lipoprotein laboratory assessments. Results and reports of these tests, together with assessment of total CV risk and the respective therapeutic targets, will help ensure that clinical guidelines and good clinical practices are followed, increasing the reliability of screening for lipid disorders, producing more accurate diagnoses and CV risk stratification, and improving CV prevention. To this end, this consensus aims to provide clinicians with practical guidance for the harmonization and standardization of laboratory lipid tests, focusing on the most recent dyslipidemia management guidelines.