Combined brain-heart MRI identifies cardiac and white matter lesions in patients with systemic lupus erythematosus and/or antiphospholipid syndrome: A pilot study.

BACKGROUND: Antiphospholipid syndrome (APS) can occur primarily (PAPS) or secondary to another autoimmune disease (SAPS), most commonly systemic lupus erythematosus (SLE). Recently, we reported that subclinical brain involvement was highly prevalent in patients with autoimmune diseases, including SLE. We aimed to investigate whether patients with SLE, PAPS or SAPS and cardiac symptoms showed differences in cardiac/brain involvement based on combined brain-heart magnetic resonance imaging (MRI). METHODS: We prospectively recruited 15 patients with SAPS (86 % with SLE) and 3 patients with PAPS and compared their MRI findings to those of 13 patients with SLE from our previous publication. All patients underwent routine cardiovascular/neurological examination and standard echocardiography. RESULTS: No patients had abnormalities in routine clinical workup/echocardiography. The vast majority had white matter hyperintensities (WMHs) and all had evidence of myocardial fibrosis and/or inflammation. Patients with SAPS had a lower median WMH number [1.00 (1.00, 2.00)] than those with PAPS [3.00 (2.50, 3.00)] or SLE [2.00 (2.00, 3.00)] (p = 0.010). Subcortical and deep WM were highly prevalent. Periventricular WMHs were more frequent in patients with SLE [6 (46.2 %)] or PAPS [2 (66.7 %)] (p = 0.023). Higher lesion burdens (1 WMH vs. 2 WMHs vs. ≥ WMHs) were associated with the presence of cardiac fibrosis [3 (33.3 %) vs. 10 (83.3) vs. 7 (77.8), p = 0.039] and affected the deep and periventricular WM (p < 0.001 for both). CONCLUSION: In patients with PAPS, SAPS or SLE, cardiac symptoms and normal routine workup, combined brain-heart MRI identified abnormalities in both organs in the majority of patients. Combined brain-heart MRI offers excellent diagnostic value, but its incorporation into routine clinical practice should be further investigated. Clinical relevance statement Combined brain-heart magnetic resonance imaging in antiphospholipid syndrome may help to assess the presence of abnormalities in both organs.

Combined Brain-Heart Imaging in Takotsubo Syndrome: Towards a Holistic Patient Assessment.

Takotsubo syndrome (TTS) is a type of cardiomyopathy usually precipitated by either emotional or physical stress and potentially leading to reversible heart failure. There is emerging evidence indicating an interaction between the brain and the heart in patients with TTS. Nevertheless, these new insights are not reflected in the current clinical approach to TTS. The application of novel and existing imaging modalities for the evaluation of brain-heart interactions is an interesting approach that could potentially augment diagnostic and prognostic yield, as well as improve our pathophysiologic understanding in the context of TTS. In this opinion piece, we discuss the evidence supporting a brain-heart interaction in patients with TTS and discuss how a combined evaluation of brain-heart interactions could potentially be implemented.

Biomarker and transcriptomics profiles of serum selenium concentrations in patients with heart failure are associated with immunoregulatory processes.

BACKGROUND: Low selenium concentrations are associated with worse outcomes in heart failure (HF). However, the underlying pathophysiologic mechanisms remain incompletely understood. Therefore, we aimed to contrast serum selenium concentrations to blood biomarker and transcriptomic profiles in patients with HF. METHODS: Circulating biomarkers, whole blood transcriptomics and serum selenium measurements in a cohort of 2328 patients with HF were utilized. Penalized linear regression and gene expression analysis were used to assess biomarker and transcriptomics profiles, respectively. As a proof-of-principle, potential causal effects of selenium on excreted cytokines concentrations were investigated using human peripheral blood mononuclear cells (PBMCs). RESULTS: Mean selenium levels were 60.6 µg/L in Q1 and 122.0 µg/L in Q4. From 356 biomarkers and 20 clinical features, the penalized linear regression model yielded 44 variables with <5 % marginal false discovery rate as predictors of serum selenium. Biomarkers associated positively with selenium concentrations included: epidermal growth factor receptor (EGFR), IFN-gamma-R1, CD4, GDF15, and IL10. Biomarkers associated negatively with selenium concentrations included: PCSK9, TNFSF13, FGF21 and PAI. Additionally, 148 RNA transcripts were found differentially expressed between high and low selenium status (Padj.<0.05; log-fold-change<|0.25|). Enrichment analyses of the selected biomarkers and RNA transcripts identified similar enriched processes, including regulation processes of leukocyte differentiation and activation, as well as cytokines production. The mRNA expression of two selenoproteins (MSRB1 and GPX4) were strongly correlated with serum selenium, while GPX4, SELENOK, and SELENOS were associated with prognosis. In the in-vitro setting, PBMCs supplemented with selenium showed significantly lower abundance of several (pro-)inflammatory cytokines. CONCLUSION: These data suggest that immunoregulation is an important mechanism through which selenium might have beneficial roles in HF. The beneficial effects of higher serum selenium concentrations are likely because of global immunomodulatory effects on the abundance of cytokines. MSRB1 and GPX4 are potential modulators of and should be pursued in future research.

Immunomodulation and immunopharmacology in heart failure.

The immune system is intimately involved in the pathophysiology of heart failure. However, it is currently underused as a therapeutic target in the clinical setting. Moreover, the development of novel immunomodulatory therapies and their investigation for the treatment of patients with heart failure are hampered by the fact that currently used, evidence-based treatments for heart failure exert multiple immunomodulatory effects. In this Review, we discuss current knowledge on how evidence-based treatments for heart failure affect the immune system in addition to their primary mechanism of action, both to inform practising physicians about these pleiotropic actions and to create a framework for the development and application of future immunomodulatory therapies. We also delineate which subpopulations of patients with heart failure might benefit from immunomodulatory treatments. Furthermore, we summarize completed and ongoing clinical trials that assess immunomodulatory treatments in heart failure and present several therapeutic targets that could be investigated in the future. Lastly, we provide future directions to leverage the immunomodulatory potential of existing treatments and to foster the investigation of novel immunomodulatory therapeutics.

Cardiac disease in Cushing's syndrome. Emphasis on the role of cardiovascular magnetic resonance imaging.

BACKGROUND: Cushing's Syndrome (CS) is associated with increased cardiovascular morbidity and mortality. In endogenous CS, cardiovascular mortality remains increased for up to 15 years post remission of hypercortisolism. Similarly, patients with exogenous CS have 4-fold increased incidence of cardiovascular events, regardless of pre-existing cardiovascular disease (CVD). OBJECTIVE: To present the pathophysiology, prognosis, clinical and imaging phenotype of cardiac disease in CS. METHODS: A Pubmed search for cardiac disease in CS over the last 20 years was conducted using combinations of relevant terms. Preclinical and clinical studies, as well as review papers reporting on subclinical heart failure (HF), cardiomyopathy, coronary heart disease (CHD), and cardiovascular imaging were selected. RESULTS: Cardiac disease in CS is associated with direct mineralocorticoid and glucocorticoid receptor activation, increased responsiveness to angiotensin II, ectopic epicardial adiposity, arterial stiffness and endothelial dysfunction, as well as with diabetes mellitus, hypertension, hyperlipidemia, obesity and prothrombotic diathesis. Subclinical HF and cardiomyopathy are principally related to direct glucocorticoid (GC) effects and markedly improve or regress post hypercortisolism remission. In contrast, CHD is related to both direct GC effects and CS comorbidities and persists post cure. In patients without clinical evidence of CVD, echocardiography and cardiac magnetic resonance (CMR) imaging reveal left ventricular hypertrophy, fibrosis, diastolic and systolic dysfunction, with the latter being underestimated by echocardiography. Finally, coronary microvascular disease is encountered in one third of cases. CONCLUSION: Cardiovascular imaging is crucial in evaluation of cardiac involvement in CS. CMR superiority in terms of reproducibility, operator independency, unrestricted field of view and capability of tissue characterisation makes this modality ideal for future studies.

Consensus on the assessment of systemic sclerosis-associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment.

Introduction: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. Methods: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. Results: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. Conclusion: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice.

Raynaud phenomenon and microvasculopathy in systemic sclerosis: multi-modality imaging for diagnosis and evaluation.

PURPOSE OF REVIEW: To describe the clinical significance of and the diagnostic approach to Raynaud phenomenon (RP) in the peripheral extremities and the heart. RECENT FINDINGS: Nailfold capillaroscopy has recently been standardized in an expert consensus paper. Abnormal capillaroscopy in combination with specific autoantibody profiles and clinical signs are highly predictive of progression of RP to systemic sclerosis (SSc). Magnetic resonance imaging (MRI) can also perform tissue characterization of both the extremities and the heart. Microvascular wall abnormalities detected using nailfold capillaroscopy in patients with SSc may lead to deposition of erythrocyte-derived iron, due to microhemorrhages, which may predispose to fibrosis. MRI can assess the presence of iron using T2∗ measurements. SUMMARY: RP is a hallmark of the microvasculopathy in SSc and can affect both the peripheral extremities and the heart. Nailfold capillaroscopy is the current gold standard for the evaluation of the peripheral microvasculature. Other imaging modalities include thermography, laser Doppler-derived methods, 99m Tc-pertechnetate hand perfusion scintigraphy, power Doppler ultrasonography, dynamic optical coherence tomography, MRI, and photoacoustic imaging, but these are currently not widely used. Cardiac RP can be investigated with positron emission tomography or cardiovascular magnetic resonance, with the latter offering the additional possibility of tissue characterization and iron content quantification secondary to microhemorrhages.

Evaluation of Senescence and Its Prevention in Doxorubicin-Induced Cardiotoxicity Using Dynamic Engineered Heart Tissues.

Background: Doxorubicin is an essential cancer treatment, but its usefulness is hampered by the occurrence of cardiotoxicity. Nevertheless, the pathophysiology underlying doxorubicin-induced cardiotoxicity and the respective molecular mechanisms are poorly understood. Recent studies have suggested involvement of cellular senescence. Objectives: The aims of this study were to establish whether senescence is present in patients with doxorubicin-induced cardiotoxicity and to investigate if this could be used as a potential treatment target. Methods: Biopsies from the left ventricles of patients with severe doxorubicin-induced cardiotoxicity were compared with control samples. Additionally, senescence-associated mechanisms were characterized in 3-dimensional dynamic engineered heart tissues (dyn-EHTs) and human pluripotent stem cell-derived cardiomyocytes. These were exposed to multiple, clinically relevant doses of doxorubicin to recapitulate patient treatment regimens. To prevent senescence, dyn-EHTs were cotreated with the senomorphic drugs 5-aminoimidazole-4-carboxamide ribonucleotide and resveratrol. Results: Senescence-related markers were significantly up-regulated in the left ventricles of patients with doxorubicin-induced cardiotoxicity. Treatment of dyn-EHTs resulted in up-regulation of similar senescence markers as seen in the patients, accompanied by tissue dilatation, decreased force generation, and increased troponin release. Treatment with senomorphic drugs led to decreased expression of senescence-associated markers, but this was not accompanied by improved function. Conclusions: Senescence was observed in the hearts of patients with severe doxorubicin-induced cardiotoxicity, and this phenotype can be modeled in vitro by exposing dyn-EHTs to repeated clinically relevant doses of doxorubicin. The senomorphic drugs 5-aminoimidazole-4-carboxamide ribonucleotide and resveratrol prevent senescence but do not result in functional improvements. These findings suggest that preventing senescence by using a senomorphic during doxorubicin administration might not prevent cardiotoxicity.

Heart Failure Post-SARS-CoV-2 Infection in Children with Duchenne Muscular Dystrophy: The Additive Value of Cardiovascular Magnetic Resonance.

In this case series, we describe the diagnosis of post-COVID-19 myocarditis in asymptomatic patients with Duchenne Muscular Dystrophy (DMD) and a mild COVID-19 disease course. These patients were referred for CMR due to electrocardiographic and echocardiographic alterations, which did not exist before COVID-19 infection. CMR identified the presence of severe myocardial inflammation in all patients based on abnormally elevated myocardial T2 ratio, late gadolinium enhancement, native T1 mapping, T2 mapping, and extracellular volume fraction. This was paired with concurrent impairment of left ventricular function. Appropriate treatment was initiated in all cases. Two of the four patients developed episodes of ventricular tachycardia during the following 6 months, and a defibrillator was implanted. Despite the mild clinical presentation, this case series demonstrates the diagnostic strength of CMR in the diagnosis and evaluation of post-COVID-19 myocarditis and serves to increase awareness of this potential complication amongst treating physicians.

Cardiovascular Magnetic Resonance Imaging as an Adjunct to the Evaluation of Cardiovascular Involvement in Diabetes Mellitus.

Diabetes mellitus (DM) is a new epidemic which has presented an immense increase in recent decades, due to the rapid increase in obesity. Cardiovascular disease (CVD) significantly reduces life expectancy and is the main cause of death in type 2 diabetes mellitus (T2DM). Strict glycemic control is a well-established method to combat microvascular CVD of type 1 diabetes mellitus (T1DM); its role against CVD of the T2DM risk has not been well documented. Therefore, the most efficient prevention is multifactorial risk factor reduction. Recently, the European Society of Cardiology published its 2019 recommendations on CVD in DM. Although all clinical points were discussed in this document, only a few comments were presented about when and how we should recommend cardiovascular (CV) imaging. Currently, CV imaging is the "must" in CV noninvasive evaluation. Alterations in CV imaging parameters can lead to early recognition of various types of CVD. In this paper, we briefly discuss the role of noninvasive imaging modalities, emphasizing the benefits of including cardiovascular magnetic resonance (CMR) in the evaluation of DM. CMR, in the same examination, can provide an assessment of tissue characterization, perfusion and function, with excellent reproducibility and without radiation or limitations, due to the body habitus. Therefore, it can play a dominant role in the prevention and risk stratification of DM. The suggested protocol for DM evaluation should include routine annual echocardiographic evaluation of all DM patients and CMR assessment of those with poorly controlled DM, microalbuminuria, heart failure, arrhythmia and recent alterations in clinical or echocardiographic evaluation.

Clinical and prognostic associations of autoantibodies recognizing adrenergic/muscarinic receptors in patients with heart failure.

AIMS: The importance of autoantibodies (AABs) against adrenergic/muscarinic receptors in heart failure (HF) is not well-understood. We investigated the prevalence and clinical/prognostic associations of four AABs recognizing the M2-muscarinic receptor or the ß1-, ß2-, or ß3-adrenergic receptor in a large and well-characterized cohort of patients with HF. METHODS AND RESULTS: Serum samples from 2256 patients with HF from the BIOSTAT-CHF cohort and 299 healthy controls were analysed using newly established chemiluminescence immunoassays. The primary outcome was a composite of all-cause mortality and HF rehospitalization at 2-year follow-up, and each outcome was also separately investigated. Collectively, 382 (16.9%) patients and 37 (12.4%) controls were seropositive for ≥1 AAB (P = 0.045). Seropositivity occurred more frequently only for anti-M2 AABs (P = 0.025). Amongst patients with HF, seropositivity was associated with the presence of comorbidities (renal disease, chronic obstructive pulmonary disease, stroke, and atrial fibrillation) and with medication use. Only anti-ß1 AAB seropositivity was associated with the primary outcome [hazard ratio (95% confidence interval): 1.37 (1.04-1.81), P = 0.024] and HF rehospitalization [1.57 (1.13-2.19), P = 0.010] in univariable analyses but remained associated only with HF rehospitalization after multivariable adjustment for the BIOSTAT-CHF risk model [1.47 (1.05-2.07), P = 0.030]. Principal component analyses showed considerable overlap in B-lymphocyte activity between seropositive and seronegative patients, based on 31 circulating biomarkers related to B-lymphocyte function. CONCLUSIONS: AAB seropositivity was not strongly associated with adverse outcomes in HF and was mostly related to the presence of comorbidities and medication use. Only anti-ß1 AABs were independently associated with HF rehospitalization. The exact clinical value of AABs remains to be elucidated.

Multifactorial Diseases of the Heart, Kidneys, Lungs, and Liver and Incident Cancer: Epidemiology and Shared Mechanisms.

Within the aging population, the frequency of cancer is increasing dramatically. In addition, multiple genetic and environmental factors lead to common multifactorial diseases, including cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and metabolic-associated fatty liver disease. In recent years, there has been a growing awareness of the connection between cancer and multifactorial diseases, as well as how one can affect the other, resulting in a vicious cycle. Although the exact mechanistic explanations behind this remain to be fully explored, some progress has been made in uncovering the common pathologic mechanisms. In this review, we focus on the nature of the link between cancer and common multifactorial conditions, as well as specific shared mechanisms, some of which may represent either preventive or therapeutic targets. Rather than organ-specific interactions, we herein focus on the shared mechanisms among the multifactorial diseases, which may explain the increased cancer risk. More research on this subject will highlight the significance of developing new drugs that target multiple systems rather than just one disease.

Cardiovascular Magnetic Resonance Demonstrates Myocardial Inflammation of Differing Etiologies and Acuities in Patients with Genetic and Inflammatory Myopathies.

INTRODUCTION: Myopathies are heterogeneous neuromuscular diseases of genetic and/or inflammatory etiology that affect both cardiac and skeletal muscle. We investigated the prevalence of cardiac inflammation in patients with myopathies, cardiovascular symptoms, and normal echocardiography using cardiovascular magnetic resonance (CMR). METHODS: We prospectively evaluated 51 patients with various genetic (n = 23) and inflammatory (n = 28) myopathies (median age, IQR: 12 (11-15) years, 22% girls; 61 (55-65) years, 46% women, respectively) and compared their CMR findings to corresponding age- and sex-matched controls (n = 21 and 20, respectively) and to each other. RESULTS: Patients with genetic myopathy had similar biventricular morphology and function to healthy controls but showed higher late gadolinium enhancement (LGE), native T1 mapping, extracellular volume fraction (ECV), and T2 mapping values. Collectively, 22 (95.7%) patients with genetic myopathy had a positive T1-criterion and 3 (13.0%) had a positive T2-criterion according to the updated Lake Louise criteria. Compared with healthy controls, patients with inflammatory myopathy showed preserved left ventricular (LV) function and reduced LV mass, while all CMR-derived tissue characterization indices were significantly higher (p < 0.001 for all). All patients had a positive T1-criterion, and 27 (96.4%) had a positive T2-criterion. A positive T2-criterion or T2-mapping > 50 ms could discriminate between patients with genetic and inflammatory myopathies with a sensitivity of 96.4% and a specificity of 91.3% (AUC = 0.9557). CONCLUSIONS: The vast majority of symptomatic patients with inflammatory myopathies and normal echocardiography show evidence of acute myocardial inflammation. In contrast, acute inflammation is rare in patients with genetic myopathies, who show evidence of chronic low-grade inflammation.

Multi-omics analyses identify molecular signatures with prognostic values in different heart failure aetiologies.

BACKGROUND: Heart failure (HF) is the leading cause of morbidity and mortality worldwide, and there is an urgent need for more global studies and data mining approaches to uncover its underlying mechanisms. Multiple omics techniques provide a more holistic molecular perspective to study pathophysiological events involved in the development of HF. METHODS: In this study, we used a label-free whole myocardium multi-omics characterization from three commonly used mouse HF models: transverse aortic constriction (TAC), myocardial infarction (MI), and homozygous Phospholamban-R14del (PLN-R14Δ/Δ). Genes, proteins, and metabolites were analysed for differential expression between each group and a corresponding control group. The core transcriptome and proteome datasets were used for enrichment analysis. For genes that were upregulated at both the RNA and protein levels in all models, clinical validation was performed by means of plasma level determination in patients with HF from the BIOSTAT-CHF cohort. RESULTS: Cell death and tissue repair-related pathways were upregulated in all preclinical models. Fatty acid oxidation, ATP metabolism, and Energy derivation processes were downregulated in all investigated HF aetiologies. Putrescine, a metabolite known for its role in cell survival and apoptosis, demonstrated a 4.9-fold (p < 0.02) increase in PLN-R14Δ/Δ, 2.7-fold (p < 0.005) increase in TAC mice, and 2.2-fold (p < 0.02) increase in MI mice. Four Biomarkers were associated with all-cause mortality (PRELP: Hazard ratio (95% confidence interval) 1.79(1.35, 2.39), p < 0.001; CKAP4: 1.38(1.21, 1.57), p < 0.001; S100A11: 1.37(1.13, 1.65), p = 0.001; Annexin A1 (ANXA1): 1.16(1.04, 1.29) p = 0.01), and three biomarkers were associated with HF-Related Rehospitalization, (PRELP: 1.88(1.4, 2.53), p < 0.001; CSTB: 1.15(1.05, 1.27), p = 0.003; CKAP4: 1.18(1.02, 1.35), P = 0.023). CONCLUSIONS: Cell death and tissue repair pathways were significantly upregulated, and ATP and energy derivation processes were significantly downregulated in all models. Common pathways and biomarkers with potential clinical and prognostic associations merit further investigation to develop optimal management and therapeutic strategies for all HF aetiologies.

Cardiovascular Magnetic Resonance Imaging Patterns in Rare Cardiovascular Diseases.

Rare cardiovascular diseases (RCDs) have low incidence but major clinical impact. RCDs' classification includes Class I-systemic circulation, Class II-pulmonary circulation, Class III-cardiomyopathies, Class IV-congenital cardiovascular diseases (CVD), Class V-cardiac tumors and CVD in malignancy, Class VI-cardiac arrhythmogenic disorders, Class VII-CVD in pregnancy, Class VIII-unclassified rare CVD. Cardiovascular Magnetic Resonance (CMR) is useful in the diagnosis/management of RCDs, as it performs angiography, function, perfusion, and tissue characterization in the same examination. Edema expressed as a high signal in STIRT2 or increased T2 mapping is common in acute/active inflammatory states. Diffuse subendocardial fibrosis, expressed as diffuse late gadolinium enhancement (LGE), is characteristic of microvascular disease as in systemic sclerosis, small vessel vasculitis, cardiac amyloidosis, and metabolic disorders. Replacement fibrosis, expressed as LGE, in the inferolateral wall of the left ventricle (LV) is typical of neuromuscular disorders. Patchy LGE with concurrent edema is typical of myocarditis, irrespective of the cause. Cardiac hypertrophy is characteristic in hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA) and Anderson-Fabry Disease (AFD), but LGE is located in the IVS, subendocardium and lateral wall in HCM, CA and AFD, respectively. Native T1 mapping is increased in HCM and CA and reduced in AFD. Magnetic resonance angiography provides information on aortopathies, such as Marfan, Turner syndrome and Takayasu vasculitis. LGE in the right ventricle is the typical finding of ARVC, but it may involve LV, leading to the diagnosis of arrhythmogenic cardiomyopathy. Tissue changes in RCDs may be detected only through parametric imaging indices.

A Gigantic Congenital Right Atrial Appendage Aneurysm in an Infant: Ten-Year Follow-Up.

A gigantic right atrial appendage aneurysm (RAAA) is a rare condition usually discovered during the third decade of life after being symptomatic. We present an asymptomatic RAAA discovered early during the basic screening of an infant and its natural history, and a ten-year follow-up due to its parents being against operation.

Pathophysiology of cognitive dysfunction and the role of combined brain/heart magnetic resonance imaging (Review).

Normal cognitive function depends on a continuous and optimally regulated blood supply, and any pathology that further reduces cerebral blood perfusion in addition to that caused by aging could damage or destroy vulnerable neurons of the brain. Furthermore, glucose serves a crucial role as the primary fuel source for the mammalian brain and any disturbance in its circulating concentrations could directly affect brain function. The term cognitive dysfunction (CD), known also as 'brain fog', refers to deficits in attention, verbal and non-verbal learning, short-term and working memory, visual and auditory processing, mathematic problem solving, processing speed, focusing on a specific topic, and motor functioning. CD is the end-point of various cardiovascular, neural, metabolic and immune function impairments. Although CD has a serious impact on patient survival and quality of life, usually it is clinically underestimated. CD is currently assessed using cognitive tests (questionnaires), which have important limitations in their diagnostic capacity, specifically in the preclinical forms of CD. Cognitive tests may not identify subclinical cases of CD but diagnose CD only when symptoms are clinically overt. Furthermore, these tests do not provide information regarding the underlying pathophysiologic background of CD. The aim of the present review is to summarize the existing literature on CD and emphasize the role of combined brain-heart magnetic resonance imaging (MRI) in its early diagnosis, before CD questionnaires are abnormal. Combined brain/heart MRI has the potential to identify patients with CD at an early stage, facilitating risk stratification and early intervention. Furthermore, in parallel with brain assessment, it provides valuable information regarding the effect of the underlying disease on the myocardium. Equipment availability, physician familiarity and cost/effectiveness should be considered before wide clinical application of combined brain/heart MRI is recommended.

The Emerging Role of Combined Brain/Heart Magnetic Resonance Imaging for the Evaluation of Brain/Heart Interaction in Heart Failure.

Heart failure (HF) patients frequently develop brain deficits that lead to cognitive dysfunction (CD), which may ultimately also affect survival. There is an important interaction between brain and heart that becomes crucial for survival in patients with HF. Our aim was to review the brain/heart interactions in HF and discuss the emerging role of combined brain/heart magnetic resonance imaging (MRI) evaluation. A scoping review of published literature was conducted in the PubMed EMBASE (OVID), Web of Science, Scopus and PsycInfo databases. Keywords for searches included heart failure, brain lesion, brain, cognitive, cognitive dysfunction, magnetic resonance imaging cardiovascular magnetic resonance imaging electroencephalogram, positron emission tomography and echocardiography. CD testing, the most commonly used diagnostic approach, can identify neither subclinical cases nor the pathophysiologic background of CD. A combined brain/heart MRI has the capability of diagnosing brain/heart lesions at an early stage and potentially facilitates treatment. Additionally, valuable information about edema, fibrosis and cardiac remodeling, provided with the use of cardiovascular magnetic resonance, can improve HF risk stratification and treatment modification. However, availability, familiarity with this modality and cost should be taken under consideration before final conclusions can be drawn. Abnormal CD testing in HF patients is a strong motivating factor for applying a combined brain/heart MRI to identify early brain/heart lesions and modify risk stratification accordingly.

Primary systemic sclerosis heart involvement: A systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition.

Introduction: Primary heart involvement in systemic sclerosis may cause morpho-functional and electrical cardiac abnormalities and is a common cause of death. The absence of a clear definition of primary heart involvement in systemic sclerosis limits our understanding and ability to focus on clinical research. We aimed to create an expert consensus definition for primary heart involvement in systemic sclerosis. Methods: A systematic literature review of cardiac involvement and manifestations in systemic sclerosis was conducted to inform an international and multi-disciplinary task force. In addition, the nominal group technique was used to derive a definition that was then subject to voting. A total of 16 clinical cases were evaluated to test face validity, feasibility, reliability and criterion validity of the newly created definition. Results: In total, 171 publications met eligibility criteria. Using the nominal group technique, experts added their opinion, provided statements to consider and ranked them to create the consensus definition, which received 100% agreement on face validity. A median 60(5-300) seconds was taken for the feasibility on a single case. Inter-rater agreement was moderate (mKappa (95% CI) = 0.56 (0.46-1.00) for the first round and 0.55 (0.44-1.00) for the second round) and intra-rater agreement was good (mKappa (95% CI) = 0.77 (0.47-1.00)). Criterion validity showed a 78 (73-84)% correctness versus gold standard. Conclusion: A preliminary primary heart involvement in systemic sclerosis consensus-based definition was created and partially validated, for use in future clinical research.