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.

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.

Coronary microvascular disease: The "Meeting Point" of Cardiology, Rheumatology and Endocrinology.

BACKGROUND: Exertional chest pain/dyspnea or chest pain at rest are the main symptoms of coronary artery disease (CAD), which are traditionally attributed to insufficiency of the epicardial coronary arteries. However, 2/3 of women and 1/3 of men with angina and 10% of patients with acute myocardial infarction have no evidence of epicardial coronary artery stenosis in X-ray coronary angiography. In these cases, coronary microvascular disease (CMD) is the main causative factor. AIMS: To present the pathophysiology of CMD in Cardiology, Rheumatology and Endocrinology. MATERIALS-METHODS: The pathophysiology of CMD in Cardiology, Rheumatology and Endocrinology was evaluated. It includes impaired microvascular vasodilatation, which leads to inability of the organism to deal with myocardial oxygen needs and, hence, development of ischemic pain. CMD, observed in inflammatory autoimmune rheumatic and endocrine/metabolic disorders, brings together Cardiology, Rheumatology and Endocrinology. Causative factors include persistent systemic inflammation and endocrine/metabolic abnormalities influencing directly the coronary microvasculature. In the past, the evaluation of microcirculation was feasible only with the use of invasive techniques, such as coronary flow reserve assessment. Currently, the application of advanced imaging modalities, such as cardiovascular magnetic resonance (CMR), can evaluate CMD non-invasively and without ionizing radiation. RESULTS: CMD may present with a variety of symptoms with 1/3 to 2/3 of them expressed as typical chest pain in effort, more commonly found in women during menopause than in men. Atypical presentation includes chest pain at rest or exertional dyspnea,but post exercise symptoms are not uncommon. The treatment with nitrates is less effective in CMD, because their vasodilator action in coronary micro-circulation is less pronounced than in the epicardial coronary arteries. DISCUSSION: Although both classic and new medications have been used in the treatment of CMD, there are still many questions regarding both the pathophysiology and the treatment of this disorder. The potential effects of anti-rheumatic and endocrine medications on the evolution of CMD need further evaluation. CONCLUSION: CMD is a multifactorial disease leading to myocardial ischemia/fibrosis alone or in combination with epicardial coronary artery disease. Endothelial dysfunction/vasospasm, systemic inflammation, and/or neuroendocrine activation may act as causative factors and bring Cardiology, Rheumatology and Endocrinology together. Currently, the application of advanced imaging modalities, and specifically CMR, allows reliable assessment of the extent and severity of CMD. These measurements should not be limited to "pure cardiac patients", as it is known that CMD affects the majority of patients with autoimmune rheumatic and endocrine/metabolic disorders.

Cardiac adiposity as a modulator of cardiovascular disease in HIV.

BACKGROUND: With the number of people living with human immunodeficiency virus (HIV) steadily increasing, cardiovascular disease has emerged as a leading cause of non-HIV related mortality. People living with HIV (PLWH) appear to be at increased risk of coronary artery disease and heart failure (HF), while the underlying mechanism appears to be multifactorial. In the general population, ectopic cardiac adiposity has been highlighted as an important modulator of accelerated coronary artery atherosclerosis, arrhythmogenesis and HF with preserved ejection fraction (HFpEF). Cardiac adiposity is also strongly linked with obesity, especially with visceral adipose tissue accumulation. AIMS: This review aims to summarize the possible role of cardiac fat depositions, assessed by imaging modalities,as potential contributors to the increased cardiac morbidity and mortality seen in PLWH, as well as therapeutic targets in the current ART era. MATERIALS & METHODS: Review of contemporary literature on this topic. DISCUSSION: Despite antiretroviral therapy (ART), PLWH have evidence of persistent, HIV-related systemic inflammation and body fat alterations. Cardiac adiposity can play an additional role in the pathogenesis of cardiovascular disease in the HIV setting. Imaging modalities such as echocardiography, cardiac multidetector computed tomography and cardiac magnetic resonance have demonstrated increased adipose tissue. Studies show that high cardiac fat depots play an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. Systemic inflammation due to HIV infection, metabolic adverse effects of ART, adipose alterations in the ageing HIV population, inflammation and immune activation are likely important mechanisms for adipose dysfunction and disproportionately occurrence of ectopic fat depots in the heart among PLWH. CONCLUSIONS: High cardiac adiposity seems to plays an additive role in promoting coronary artery atherosclerosis and HFpEF in PLWH. The underlying mechanisms are multiple and warrant further investigation. Improved understanding of the regulating mechanisms that increase cardiovascular risk in HIV infection may give rise to more tailored therapeutic strategies targeting cardiac fat depots.

The Additive Prognostic Value of Serial Plasma Interleukin-6 Levels over Changes in Brain Natriuretic Peptide in Patients with Acute Heart Failure.

BACKGROUND: Elevated plasma interleukin-6 (IL-6) concentrations are frequently observed in patients with acute heart failure (AHF). However, the predictive value of serial IL-6 measurements beyond brain natriuretic peptide (BNP) remains poorly characterized. METHODS AND RESULTS: This was a retrospective analysis of the PROTECT cohort (2033 patients with AHF). Plasma IL-6 and BNP levels were determined on days 1, 2, 7 and 14 after admission for AHF in 1591 (78.3%), 1462 (71.9%), 1445 (71.1%) and 1451 (71.4%) patients, respectively. The primary endpoint was 180-day all-cause mortality. The median day-1 IL-6 concentration was 11.1 pg/mL (IQR: 6.6, 20.9) and decreased to 10.1 pg/mL (IQR: 5.6-18.5) at day-7. Higher cross-sectional IL-6 concentrations at all time-points predicted the primary endpoint, independent of a risk model for this cohort and changes in BNP. Each doubling of IL-6 between day-1 and day-7 predicted the primary endpoint independent of baseline IL-6 concentrations, the risk model, baseline BNP and changes in BNP [HR (95% CI): 1.18 (1.07-1.30), p=0.0013]. Collectively, 214 (17%) patients experienced at least a doubling of their IL-6 concentrations between day-1 and day-7. CONCLUSIONS: We demonstrate that the temporal evolution patterns of IL-6 in patients with AHF have additive prognostic value independent of changes in BNP.

Cardiac amyloidosis: in search of the ideal diagnostic tool.

BACKGROUND: Cardiac amyloidosis (CA) is due to amyloid deposition in the myocardium. Transthyretin (ATTR) and light-chain (AL) amyloidosis are the main types of CA. Here, we present the clinical and imaging findings in patients with CA and discuss the controversies with the aim of finding the ideal diagnostic tool. METHODS: Ten patients suspected of having CA on the basis of electrocardiographic (ECG) and echocardiographic findings were evaluated via cardiovascular magnetic resonance imaging (CMR; 1.5 T) using cine, late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction. N­terminal pro-B-type natriuretic peptide (NT-proBNP) levels were also assessed in all patients. RESULTS: All ten patients had an echocardiogram suggestive of CA. The CMR study documented ventricular hypertrophy leading to small ventricular volumes, as assessed by echocardiography. Diffuse subendocardial LGE, supporting the diagnosis of CA, was identified in all except one patient, who had subepicardial LGE due to myocarditis that was verified by endomyocardial biopsy (EMB). Right ventricular (RV) involvement was identified in four of the ten patients, whose condition deteriorated rapidly over the next 6 months. The NT-proBNP levels were >332 pg/ml in all except two patients. Light-chain amyloidosis was identified via fat tissue biopsy in two patients and through renal biopsy in one patient. In two patients with positive technetium-99m, EMB confirmed the diagnosis of ATTR. CONCLUSION: NT-proBNP may be a sensitive but nonspecific biomarker for assessing CA. However, CMR is the only imaging modality that can assess the pathophysiologic background of cardiac hypertrophy and the severity of CA, irrespective of NT-proBNP level.

Tissue Characterization in Cardiology: Moving Beyond Function.

Cardiovascular Magnetic Resonance (CMR) offers accurate and highly reproducible tissue characterization, beyond cardiac function. Late gadolinium enhancement (LGE), although represents a noninvasive biopsy for fibrosis quantification, it is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) are able to provide important information about processes involving both myocardial cells and interstitium that otherwise cannot be identified. Changes in myocardial native T1 mapping reflect cardiac diseases such as acute coronary syndromes, myocardial infarction, myocarditis, diffuse fibrosis, systemic disease such as cardiac amyloidosis, all presented with high T1 and Anderson-Fabry disease and siderosis, presented with low T1 mapping. The ECV, an index generated by native and postcontrast T1 mapping, introduces a new way to measure the cellular and extracellular interstitial matrix (ECM). ECV has a prognostic value equal to Left ventricular ejection fraction (LVEF); however, LVEF underscores the interstitial matrix. This myocyte-ECM dichotomy has important implications for identifying therapeutic targets that are of great value for heart failure (HF) treatment. Furthermore, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset HF. These indices will affect significantly the clinical decision making. However, there is still lack of multicenter studies and community-wide approach including MRI vendors, clinicians, fundings, softwares, and contrast agent manufacturers.

Cardiac magnetic resonance predicts ventricular arrhythmias in scleroderma: the Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS).

OBJECTIVES: Cardiac rhythm disturbances constitute the most frequent cardiovascular cause of death in SSc. However, electrocardiographic findings are not a part of risk stratification in SSc. We aimed to translate 24 h Holter findings into a tangible risk prediction score using cardiovascular magnetic resonance. METHODS: The Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS) was a prospective multicentre study including 150 consecutive SSc patients from eight European centres, assessed with 24 h Holter and cardiovascular magnetic resonance, including ventricular function, oedema (T2 ratio) and late gadolinium enhancement (%LGE). Laboratory/clinical parameters were included in multivariable corrections. A combined endpoint of sustained ventricular tachycardia requiring hospitalization and sudden cardiac death at a median (interquartile range) follow-up of 1 (1.0-1.4) year was generated. RESULTS: Only T2 ratio and %LGE were significant predictors of ventricular rhythm disturbances, but not of supraventricular rhythm disturbances, after multivariable correction and adjustment for multiple comparisons. Using decision-tree analysis, we created the SAnCtUS score, a four-category scoring system based on T2 ratio and %LGE, for identifying SSc patients at high risk of experiencing ventricular rhythm disturbance at baseline. Increasing SAnCtUS scores were associated with a greater disease and arrhythmic burden. All cases of non-sustained ventricular tachycardia (n = 7) occurred in patients with the highest SAnCtUS score (=4). Having a score of 4 conveyed a higher risk of reaching the combined endpoint in multivariable Cox regression compared with scores 1/2/3 [hazard ratio (95% CI): 3.86 (1.14, 13.04), P = 0.029] independently of left ventricular ejection fraction and baseline ventricular tachycardia occurrence. CONCLUSION: T2 ratio and %LGE had the greatest utility as independent predictors of rhythm disturbances in SSc patients.

The pivotal role of cardiovascular imaging in the identification and risk stratification of non-compaction cardiomyopathy patients.

Non-compaction cardiomyopathy (NCM) is a heterogeneous myocardial disease that can finally lead to heart failure, arrhythmias, and/or embolic events. Therefore, early diagnosis and treatment is of paramount importance. Furthermore, genetic assessment and counseling are crucial for individual risk assessment and family planning. Echocardiography is the first-line imaging modality. However, it is hampered by interobserver variability, depends among others on the quality of the acoustic window, cannot assess reliably the right ventricle and the apex, and cannot provide tissue characterization. Cardiovascular magnetic resonance (CMR) provides a 3D approach allowing imaging of the entire heart, including both left and right ventricle, with low operator variability or limitations due to patient's body structure. Furthermore, tissue characterization, using late gadolinium enhancement (LGE), allows the detection of fibrotic areas possibly representing the substrate for potentially lethal arrhythmias, predicts the severity of LV systolic dysfunction, and differentiates apical thrombus from fibrosis. Conversely, besides being associated with high costs, CMR has long acquisition/processing times, lack of expertise among cardiologists/radiologists, and limited availability. Additionally, in cases of respiratory and/or cardiac motion artifacts or arrhythmias, the cine images may be blurred. However, CMR cannot be applied to patients with not CMR-compatible implanted devices and LGE may be not available in patients with severely reduced GFR. Nevertheless, native T1 mapping can provide detailed tissue characterization in such cases. This tremendous potential of CMR makes this modality the ideal tool for better risk stratification of NCM patient, based not only on functional but also on tissue characterization information.

Is There a Brain/Heart Interaction in Rheumatoid Arthritis and Seronegative Spondyloartropathies? A Combined Brain/Heart Magnetic Resonance Imaging Reveals the Answer.

PURPOSE OF REVIEW: To present the interaction between brain/heart and emphasize the role of combined brain/heart magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and other seronegative spondyloarthropathies (SNA). RECENT FINDINGS: Both traditional cardiovascular disease (CVD) risk factors and intrinsic RA/SNA features contribute to the increased CVD-related morbidity/mortality. CVD in RA usually occurs a decade earlier than age- and sex-matched controls, and RA patients are twice more likely to develop myocardial infarction irrespective of age, history of prior CVD, and traditional CVD risk factors. RA also increases risk of non-ischemic heart failure (HF), valvular disease, and myo-pericarditis. CVD in SNA affects more commonly patients with long-standing disease. Ascending aortitis, aortic/mitral insufficiency, conduction defects, and diastolic dysfunction are the commonest findings in ankylosing spondylitis (AS). CVD is also the leading cause of death in psoriatic arthritis (PsA), due to myopericarditis, diastolic dysfunction, and valvular disease. Brain damage, due to either ischemic or hemorrhagic stroke and silent vascular damage, such as white matter hyperenhancement (WMH), is increased in both RA/SNA and may lead to cognitive dysfunction, depression, and brain atrophy. Magnetic resonance imaging (MRI) is ideal for serial brain/heart evaluation of patients with systemic diseases. RA/SNA patients are at high risk for brain/heart damage at early age, irrespectively of classic risk factors. Until more data will be obtained, a combined brain/heart MRI evaluation can be proposed in RA/SNA with new onset of arrhythmia and/or HF, cognitive dysfunction and/or depression.

Current understanding and future perspectives of brain-heart-kidney axis in psoriatic arthritis.

Psoriatic arthritis (PsA) patients are at a higher risk of systemic inflammatory sequelae, leading to microalbuminuria, cardiovascular (CVD) and neuropsychiatric (NPD) disease. Our aim is to present the existing literature about the relationship between CVD, kidney and NPD in PsA. The literature evaluation of PsA revealed that chronic T-cell activation and increased levels of circulating immune complexes can cause glomerular injury leading to microalbuminuria, which predicts CVD and all-cause mortality in both diabetic and non-diabetic patients. Furthermore, it is a marker of preclinical brain damage and identifies patients at higher risk of NPD/CVD events. Among the currently used imaging modalities in PsA, magnetic resonance imaging (MRI) maintains a crucial role, because it is ideal for concurrent evaluation of brain/heart involvement and serial follow up assessment. There is increasing evidence regarding the relationship between kidneys, heart and brain in PsA. Although currently there are no official recommendations about a combined brain/heart MRI in PsA, it could be considered in PsA with microalbuminuria, arrhythmia, HF, cognitive dysfunction and/or depression.

Myocardial Involvement in Rheumatic Disorders.

PURPOSE OF REVIEW: Autoimmune rheumatic diseases (ARDs) affect 8% of the population and approximately 78% of patients are women. Myocardial disease in ARDs is the endpoint of various pathophysiologic mechanisms including atherosclerosis, valvular disease, systemic, myocardial, and/or vascular inflammation, as well as myocardial ischemia and replacement/diffuse fibrosis. RECENT FINDINGS: The increased risk of CVD in ARDs leads to excess comorbidity not fully explained by traditional cardiovascular risk factors. It seems that the chronic inflammatory status typically seen in ARDs, promotes both the development of myocardial inflammation/fibrosis and the acceleration of atherosclerosis. CMR (cardio-vascular magnetic resonance) is the ideal imaging modality for the evaluation of cardiac involvement in patients with ARDs, as it can simultaneously assess cardiac function and characterize myocardial tissues with regard to oedema and fibrosis. Due to its high spatial resolution, CMR is capable of identifying various disease entities such as myocardial oedema /inflammation, subendocardial vasculitis and myocardial fibrosis, that are often missed by other imaging modalities, notably at an early stage of development. Although generally accepted guidelines about the application of CMR in ARDs have not yet been formulated, according to our experience and the available published literature, we recommend CMR in ARD patientS with new-onset heart failure (HF), arrhythmia, for treatment evaluation/change or if there is any mismatch between patient symptoms and routine non-invasive evaluation.

Pathophysiology and imaging of heart failure in women with autoimmune rheumatic diseases.

Autoimmune rheumatic diseases (ARDs) affect 8% of the population, and approximately 78% of them are women. Cardiovascular disease (CVD) in ARDs encompasses different pathophysiologic processes, such as endothelial dysfunction, myocardial/vascular inflammation and accelerated atherosclerosis with silent clinical presentation, leading to heart failure (HF), usually with preserved ejection fraction. Echocardiography and cardiovascular magnetic resonance (CMR) are the two most commonly used noninvasive imaging modalities for the evaluation of HF in patients with ARDs. Echocardiography currently represents the main diagnostic tool for cardiac imaging in clinical practice. However, the demand for more efficient and prompt diagnostic and therapeutic approach in this specific population necessitates the implementation of modalities capable of providing a more detailed and quantified information from the point of tissue characterization. Furthermore, echocardiography is an operator and acoustic window depended modality, with relatively low reproducibility and unable to perform tissue characterization. CMR is a noninvasive modality without radiation that can give reproducible and operator-independent information about both myocardial function and tissue characterization. By providing quantification of oedema, stress perfusion defects and fibrosis, CMR can diagnose myocardial inflammation, micro-macro-vascular myocardial ischemia and replacement or diffuse fibrosis, respectively. Tissue characterization allows for moving beyond the cardiac function to the assessment of intra- and inter-cellular alterations and promotes the development of personalized cardiac and anti-rheumatic treatment in ARDs with HF. ARDs are mainly female diseases. Cardiac involvement leading in HF is not unusual in ARDs and remains the main cause of death. Noninvasive, nonradiating imaging modalities such as echocardiography and CMR represent the main diagnostic tools. Specifically, echocardiography represents the first diagnostic approach; however, it is CMR that gives information about the pathophysiologic background behind HF in ARDs.

Cardio-oncology, the myth of Sisyphus, and cardiovascular disease in breast cancer survivors.

The number of breast cancer (BC) survivors has been increasing lately, due to the improvement in early detection strategies and oncological treatments. However, BC survivors are 3 times as likely to develop heart failure (HF) within 5 years of cancer diagnosis, and 7/100 of them will develop HF in a median follow-up of 8.5 years. Furthermore, HF in BC survivors has a worse prognosis compared to other causes of HF. Anthracyclines and trastuzumab have been proven to improve survival. However, they are also considered as the main causative factors of HF in BC survivors. Old patients, those with a pre-existing cardiovascular (CV) risk factors/disease, prior exposure to chemotherapy and radiotherapy are at increased risk. Serial evaluation of troponins and cardiac imaging parameters using echocardiography and cardiovascular magnetic resonance can significantly contribute to the early diagnosis of cardiac involvement before overt HF will develop. Assessment and immediate treatment of traditional CV risk factors is the first step for cardiotoxicity prevention. In BC survivors with known heart disease, the clinical stabilization is strongly recommended for cardiotoxicity prevention. Finally, in high-risk CV patients, primary prevention including cardioprotectants and/or CV drugs should be applied. According to recent studies, the early start of ACE inhibitors and ß-blockers and the modification of anti-cancer treatment can prevent the decline in left ventricular ejection fraction. However, further multicenter studies are needed to establish both prevention and treatment protocols to successfully overcome HF development in BC survivors.

Combined brain and heart magnetic resonance imaging in systemic vasculitides: fiction or real need?

Systemic vasculitides (SVs) is a group of diseases characterised by inflammation/necrosis of the blood vessel wall in various organs. Simultaneous brain and heart involvement is a cause of increased morbidity/mortality in SV. We aimed to present evidence of concurrent brain/heart involvement in SV and the role of a combined brain/heart magnetic resonance imaging (MRI) in their risk stratification. Cerebral vasculitis (CV) can be presented as focal deficits, seizures, headache, neuropsychiatric manifestations or cognitive dysfunction and cardiovascular disease (CVD) as myocardial/vascular inflammation, perfusion/function defects and fibrosis. MRI is a non-invasive, non-radiating technique that allows the reliable identification of intraparenchymal brain lesions and the detection of myocardial/vascular inflammation and fibrosis. However, its use in SV is currently hampered by high cost, lack of availability/expertise and lack of awareness among the clinicians. Although there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SV, it would be called for in cases with clinical suspicion of brain/heart involvement, especially in those at high risk for CVD/stroke such as SLE/APS. Furthermore, it may be of value in SV with multi-organ involvement, cognitive dysfunction or other neuropsychiatric symptoms with concurrent cardiac involvement, presenting as typical or atypical symptoms with normal routine cardiac evaluation, new onset of arrhythmia and/or HF.

Can cardiovascular magnetic resonance prompt early cardiovascular/rheumatic treatment in autoimmune rheumatic diseases? Current practice and future perspectives.

Life expectancy in autoimmune rheumatic diseases (ARDs) remains lower compared to the general population, due to various comoborbidities. Cardiovascular disease (CVD) represents the main contributor to premature mortality. Conventional and biologic disease-modifying antirheumatic drugs (DMARDs) have considerably improved long-term outcomes in ARDs not only by suppressing systemic inflammation but also by lowering CVD burden. Regarding atherosclerotic disease prevention, EULAR has recommended tight disease control accompanied by regular assessment of traditional CVD risk factors and lifestyle changes. However, this approach, although rational and evidence-based, does not account for important issues such as myocardial inflammation and the long asymptomatic period that usually proceeds clinical manifestations of CVD disease in ARDs before or after the diagnosis of systemic disease. Cardiovascular magnetic resonance (CMR) can offer reliable, reproducible and operator independent information regarding myocardial inflammation, ischemia and fibrosis. Some studies suggest a role for CMR in the risk stratification of ARDs and demonstrate that oedema/fibrosis visualisation with CMR may have the potential to inform cardiac and rheumatic treatment modification in ARDs with or without abnormal routine cardiac evaluation. In this review, we discuss how CMR findings could influence anti-rheumatic treatment decisions targeting optimal control of both systemic and myocardial inflammation irrespective of clinical manifestations of cardiac disease. CMR can provide a different approach that is very promising for risk stratification and treatment modification; however, further studies are needed before the inclusion of CMR in the routine evaluation and treatment of patients with ARDs.

Prospects of using cardiovascular magnetic resonance in the identification of arrhythmogenic substrate in autoimmune rheumatic diseases.

Sudden cardiac death (SCD) is due to ventricular tachycardia/fibrillation (VT/VF) and may occur with or without any structural or functional heart disease. The presence of myocardial edema, ischemia and/or fibrosis plays a crucial role in the pathogenesis of VT/VF, irrespective of the pathophysiologic background of the disease. Specifically, in autoimmune rheumatic diseases (ARDs), various entities such as myocardial/vascular inflammation, ischemia and fibrosis may lead to VT/VF. Furthermore, autonomic dysfunction, commonly found in ARDs, may also contribute to SCD in these patients. The only non-invasive, radiation-free imaging modality that can perform functional assessment and tissue characterization is cardiovascular magnetic resonance (CMR). Due to its capability to detect and quantify edema, ischemia and fibrosis in parallel with ventricular function assessment, CMR has the great potential to identify ARD patients at high risk for VT/VF, thus influencing both cardiac and anti-rheumatic treatment and modifying perhaps the criteria for implantation of cardioverter defibrillators.

Oedema-fibrosis in Duchenne Muscular Dystrophy: Role of cardiovascular magnetic resonance imaging.

Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by progressive, irreversible loss of cardiac and skeletal muscular function. Muscular enlargement in DMD is attributed to oedema, due to the increased cytoplasmic Na+ concentration. The aim of this review was to present the current experience and emphasize the role of cardiovascular magnetic resonance (CMR) in the diagnosis of this condition. DMD patients' survival depends on ventilatory assistance, as respiratory muscle dysfunction was the most common cause of death in the past. Currently, due to improved ventilatory assistance, cardiomyopathy has become the main cause of death, even though clinically overt heart failure may be absent. CMR is the technique of choice to assess the pathophysiologic phenomena taking place in DMD, such as myocardial oedema and subepicardial fibrosis. The classic index to assess oedema is the T2-weighted short-tau inversion recovery (T2w-STIR), as it suppresses the signal from flowing blood and resident fat and enhances sensitivity to tissue fluid. Furthermore, CMR is the most reliable technique to detect and quantify fibrosis in DMD. Recently, the new indices T2, T1 mapping (native and postcontrast) and the extracellular volume (ECV) allow a more accurate approach of myocardial oedema and fibrosis. To conclude, the assessment of cardiac oedema and subepicardial fibrosis in the inferolateral wall of the left heart ventricle are the most important early finding in DMD with preserved ventricular function, and CMR, using both the classic and the new indices, is the best technique to detect and monitor these lesions.

Cardiac profile of asymptomatic children with Becker and Duchenne muscular dystrophy under treatment with steroids and with/without perindopril.

BACKGROUND: To evaluate cardiovascular function in boys with Duchenne (DMD) and Becker (BMD) muscular dystrophy, using cardiac magnetic resonance (CMR). METHODS: This is a single point cross sectional study of twenty-four boys with genetically ascertained DMD, and 10 with BMD, aged 10.5 ± 1.5 years (range 9-13), were prospectively evaluated by a 1.5 T system and compared with those of age-sex matched controls. The DMD patients were divided in 2 groups. Group A (N = 12) were under treatment with both deflazacort and perindopril, while Group B (n = 12) were under treatment with deflazacort, only. BMD patients did not take any medication. Biventricular function was assessed using a standard SSFP sequence. Late gadolinium enhancement (LGE) was assessed from T1 images taken 15 min after injection of 0.2 mg/Kg gadolinium DTPA using a 3D-T1-TFE sequence. RESULTS: Group A and BMDs were asymptomatic with normal ECG, 24 h ECG recording and echocardiogram. Group B were asymptomatic but 6/12 had abnormal ECG and mildly impaired LVEF. Their 24 h ECG recording revealed supraventricular and ventricular extrasystoles (all at 12-13 yrs). LV indices in Group A and BMD did not differ from those of controls. However, LV indices in Group B were significantly impaired compared with controls, Group A and BMDs (p < 0.001). An epicardial LGE area = 3 ± 0.5% of LV mass was identified in the posterolateral wall of LV only in 6/12 patients of Group B, but in not in any BMD or Group A. CONCLUSION: Children with either BMD or DMD under treatment with both deflazacort and perindopril present preserved LV function and lack of LGE. However, further large scale multicenter studies are warranted to confirm these data, including further CMR mapping approaches.