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.

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.

Diagnosis and management of primary heart involvement in systemic sclerosis.

PURPOSE OF REVIEW: In systemic sclerosis (SSc) primary heart involvement (pHI) is frequent, even though often unrecognized due to its occult nature and to the lack of a specific diagnostic algorithm. The purpose of this review is to report the state of the art of the evidence in the current literature, as well as the overall diagnostic modalities and therapeutic strategies for primary heart involvement in SSc. RECENT FINDINGS: SSc-pHI is defined by the presence of cardiac abnormalities that are predominantly attributable to SSc rather than other causes and/or complications; it may be sub-clinical and must be confirmed through diagnostic investigations. Novel electrocardiographic analysis and cardiac magnetic resonance (CMR) with mapping techniques have been recently proposed, showing a great utility in the early identification of SSc-pHI and in the noninvasive characterization of myocardial tissue. Immunosuppressive therapy emerged as fundamental to curb myocardial inflammation, and recent preclinical and clinical data support the role of antifibrotic drugs to treat SSc-pHI. SUMMARY: our review will help clinicians to properly integrate the available diagnostic modalities for the assessment of SSc-pHI. The ultimate goal is to propose a feasible diagnostic algorithm for the early identification of patients with SSc-pHI, and a schematic therapeutic approach to manage SSc-pHI.

Novel Imaging Approaches to Cardiac Manifestations of Systemic Inflammatory Diseases: JACC Scientific Statement.

Derangements in the innate and adaptive immune responses observed in systemic inflammatory syndromes contributes to unique elevated atherosclerotic risk and incident cardiovascular disease. Novel multimodality imaging techniques may improve diagnostic precision for the screening and monitoring of disease activity. The integrated application of these technologies lead to earlier diagnosis and noninvasive monitoring of cardiac involvement in systemic inflammatory diseases that will aid in preclinical studies, enhance patient selection, and provide surrogate endpoints in clinical trials, thereby improving clinical outcomes. We review the common cardiovascular manifestations of immune-mediated systemic inflammatory diseases and address the clinical and investigational role of advanced multimodality cardiac imaging.

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.

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.

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 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.

Cardiovascular magnetic resonance for the evaluation of patients with cardiovascular disease: An overview of current indications, limitations, and procedures.

Cardiovascular disease (CVD) is the most common cause of morbidity/mortality worldwide. Early diagnosis is the key to improve CVD prognosis, and cardiovascular imaging plays a crucial role in this direction. Echocardiography is the most commonly used imaging modality. However, the need for early diagnosis/treatment favors the development of modalities providing information about tissue characterization beyond echocardiography. In this context, the rapid evolution of cardiovascular magnetic resonance (CMR) led to the coexistence of cardiologists and radiologists in the CMR field. Our aim was to provide an overview of indications, sequences, and reporting of CMR findings in various CVDs. The indications/limitations of CMR as well as the pathophysiological significance of various sequences in adult/pediatric CVDs are presented and discussed in detail. The role of CMR indices in the evaluation of the most common clinical scenarios in cardiology and their impact on CVD diagnosis/prognosis were analyzed in detail. Additionally, the comparison of CMR versus other imaging modalities is also discussed. Finally, future research directions are presented. CMR can provide cardiac tissue characterization and biventricular/biatrial functional assessment in the same examination, allowing for early and accurate identification of important subclinical abnormalities, before clinically overt CVD takes place.

Cardiovascular Magnetic Resonance for the Evaluation of Arrhythmogenic Substrates in Patients with Systemic Autoimmunity: An Update.

Patients with systemic autoimmunity due to autoimmune rheumatic diseases (ARDs) or sarcoidosis frequently present with systemic manifestations including cardiac involvement. Cardiac rhythm disturbances and specifically ventricular arrhythmias (VAs) may affect the prognosis of these patients. Cardiovascular magnetic resonance imaging (CMR) is a non-invasive imaging modality that can provide valuable diagnostic and prognostic information in patients with ARDs or systemic autoimmunity in general. In this narrative review, we briefly present the underlying pathophysiologic mechanisms contributing to arrhythmogenicity in patients with systemic autoimmunity. Furthermore, we discuss recent advances underlying the role and value of CMR for use in the detection and risk stratification of arrhythmogenic substrates in patients with systemic autoimmunity and VAs.

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.

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.

Rare Metabolic and Endocrine Diseases with Cardiovascular Involvement: Insights from Cardiovascular Magnetic Resonance - A Review.

The identification of rare diseases with cardiovascular involvement poses significant diagnostic challenges due to the rarity of the diseases, but also due to the lack of knowledge and expertise. Most of them remain underrecognized and undiagnosed, leading to clinical mismanagement and affecting the patients' prognosis, as these diseases are per definition life-threatening or chronic debilitating. This article reviews the cardiovascular involvement of the most well-known rare metabolic and endocrine diseases and their diagnostic approach through the lens of cardiovascular magnetic resonance (CMR) imaging and its prognostic role, highlighting its fundamental value compared to other imaging modalities.

Cardiovascular Magnetic Resonance Detects Inflammatory Cardiomyopathy in Symptomatic Patients with Inflammatory Joint Diseases and a Normal Routine Workup.

Background. Patients with inflammatory joint diseases (IJD) are more likely to develop cardiovascular disease compared with the general population. We hypothesized that cardiovascular magnetic resonance (CMR) could identify cardiac abnormalities in patients with IJD and atypical symptoms unexplained by routine clinical evaluation. Patients-Methods. A total of 51 consecutive patients with IJD (32 with rheumatoid arthritis, 10 with ankylosing spondylitis, and 9 with psoriatic arthritis) and normal clinical, electrocardiographic and echocardiographic workups, were referred for CMR evaluation due to atypical chest pain, shortness of breath, and/or palpitations. Their CMR findings were compared with those of 40 non-IJD controls who were referred for the same reason. All participants were examined using either a 1.5 T or 3.0 T CMR system. For T1/T2 mapping, comparisons were performed separately for each field strength. Results. Biventricular systolic function was similar between groups. In total, 25 (49%) patients with IJD vs. 0 (0%) controls had replacement-type myocardial fibrosis (p < 0.001). The T2 signal ratio, early/late gadolinium enhancement, and extracellular volume fraction were significantly higher in the IJD group. Native T1 mapping was significantly higher in patients with IJD independent of the MRI field strength (p < 0.001 for both). T2 mapping was significantly higher in patients with IJD compared with controls only in those examined using a 1.5 T MR system­52.0 (50.0, 55.0) vs. 37.0 (33.5, 39.5), p < 0.001. Conclusions. In patients with IJD and a mismatch between cardiac symptoms and routine non-invasive evaluation, CMR uniquely identified a significant proportion of patients with myocardial inflammation. A CMR examination should be considered in patients with IJD in similar clinical settings.

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.

Cardiovascular Magnetic Resonance Reveals Cardiac Pathophysiology in Autoimmune Rheumatic Diseases.

BACKGROUND/AIMS: The high incidence of cardiovascular disease (CVD) in patients with autoimmune rheumatic diseases (ARDs) is the main driver towards increased mortality in this patient group. Cardiovascular magnetic resonance (CMR) can non-invasively and robustly detect CVD in ARD patients at an early stage of development. The review summarises the diagnostic information provided by CMR in ARD patients. SUMMARY: CMR uses a strong magnetic field combined with radio-frequency pulses (pulse sequences) to generate images. Firstly, balanced steady-state free precession (bSSFP) can be used for evaluating cardiac anatomy, mass, wall motion, atrial/ventricular function. Secondly, T2-weighted imaging (T2-W) can be used for oedema detection, which appears as a high signal intensity area on STIR (short tau inversion recovery) images. T2 mapping is a newer T2-W technique that can provide more optimal identification of myocardial oedema. Lastly, late gadolinium enhanced (LGE) T1-W images, taken 15 min. after injection of contrast agent, allow the detection of myocardial replacement fibrosis, which appears as a bright area in a background of black myocardium. However, LGE has inherent disadvantages for the assessment of diffuse myocardial fibrosis. Therefore, T1 mapping and extracellular volume fraction (ECV) have been developed to quantify diffuse myocardial fibrosis. RESULTS: Although multicentre studies are still missing, the CMR parameters have been extensively applied for the identification of oedema/fibrosis and treatment decision making in ARDs. CONCLUSIONS: Tissue characterisation with CMR allows early and robust identification of CVD in ARD patients and contributes to personalized management in the patients.