Background: Autoimmune rheumatic diseases (ARDs) often present diagnostic challenges, particularly in undifferentiated disease or overlap syndromes. Autoantibodies (AABs) serve as early biomarkers, but their relationship with cardiac involvement during the prodromal phase remains unclear. We hypothesized that cardiac involvement is an early, unifying feature in AAB-seropositive patients with suspected ARD/overlap syndromes but an as-of-yet unclear diagnosis. Methods: We prospectively recruited 18 treatment-naïve patients (mean age 52 ± 17 years, 94.4% women) with suspected undifferentiated ARD/overlap syndromes who were seropositive for myositis-specific (MSAs), myositis-associated (MAAs), or scleroderma-specific autoantibodies (SScSAs). All underwent comprehensive rheumatologic, pulmonologic, and cardiac evaluations, including multiparametric cardiovascular magnetic resonance (CMR) to assess myocardial inflammation, edema, and fibrosis. Results: Despite normal echocardiograms, electrocardiograms, and inflammatory biomarkers, all patients exhibited CMR evidence of cardiac involvement. Active myocardial inflammation (revised Lake Louise criteria) was confirmed in 66.7%, while subepicardial fibrosis was universal (median 5.0% of LV mass). During the 12-month follow-up, all patients with evidence of inflammation received immunosuppressive and cardioprotective therapy, leading to symptomatic improvement in all and reduced inflammation in 75% of repeat CMRs (3/4 patients). A definitive rheumatologic diagnosis was established in all cases, with 50% classified as overlap syndromes. Conclusions: Cardiac involvement is a highly prevalent disease manifestation in AAB-seropositive patients with suspected ARD/overlap syndromes and can be detected by CMR during the prodromal phase, even before diagnostic criteria are met. These findings support early CMR integration in the workup of such patients to guide timely immunosuppressive and cardioprotective interventions.

One-third of the mortality in autoimmune rheumatic diseases (ARDs) is due to cardiovascular disease (CVD). CVD in ARDs includes: (1) macro- or microvascular coronary artery disease (CAD), (2) inflammatory cardiomyopathy, due to myocardial microvasculopathy, myopericarditis, (3) heart failure with preserved ejection fraction or reduced ejection fraction, (4) valvular heart disease, and (5) non-coronary vascular disease. Cardiovascular magnetic resonance (CMR), a noninvasive imaging modality, provides functional and tissue characterization information and is the ideal tool for diagnosis/follow-up of CVD in ARDs. Both classic and new parametric indices strongly support the role of CMR as a potent diagnostic modality for cardiovascular evaluation in patients with ARDs.

There are only few reports in the literature regarding McLeod Syndrome and cardiomyopathy and all of them are referred to adults with neurological symptoms and hyperCKemia. To our knowledge, this is the first reported case of a neurologically asymptomatic 14-year-old male adolescent with hyperCKemia and dilated cardiomyopathy, due to McLeod syndrome. In our patient, the documentation of clinical suspicion of McLeod syndrome was achieved by genetic assessment. Our clinical awareness guided the decision to perform a cardiovascular magnetic resonance (CMR) evaluation although the echocardiogram was normal. The lack of neurological symptoms can be attributed to the young age of the patient, since neurological symptoms usually start from 25 to 60 years of age. However, nothing is known about the age of cardiomyopathy development. Again, there is no evidence from the literature that dilated cardiomyopathy can precede the development of neurological symptoms. There is only one case in the literature presenting the coexistence of dilated cardiomyopathy, due to myocarditis and McLeod syndrome, but in our patient no history of myocarditis was identified and the CMR showed lack of myocardial oedema, indicative of myocarditis.

Systemic sclerosis (SSc) is a chronic rheumatic disease characterized by the unique pathogenetic triad of microvasculopathy, autoimmunity, and fibrosis leading to significant morbidity/mortality. SSc has an annual incidence of 0.6 to 5.6/100 000, affects predominantly women and remains the most lethal of rheumatic diseases being the direct cause of death in >50% of patients. SSc with diffuse cutaneous involvement is defined as skin thickening proximal to the elbows/knees, whereas the limited form denotes cutaneous involvement limited to the distal extremities. Pulmonary fibrosis, pulmonary hypertension, and cardiac inflammation/fibrosis, although varying widely among patients in terms of severity, represent the main causes of death. Primary heart involvement occurs in the majority of patients at some disease stage but is overlooked. It may precede SSc diagnosis and should be carefully monitored using laboratory and imaging biomarkers. Among imaging biomarkers, echocardiography and cardiac magnetic resonance are the most commonly used. Echocardiography can provide functional information of both ventricles and assessment of pulmonary artery pressure. Additionally, strain echocardiography and cardiac magnetic resonance feature tracking can detect early systolic dysfunction before ejection fraction alterations take place. However, cardiac magnetic resonance, by providing functional assessment in parallel with tissue characterization, is the only imaging modality that has the potential to reveal early myocardial inflammation/replacement/diffuse fibrosis and coronary microvascular disease before any systolic alteration takes place. Prospective, multicenter studies that are currently under way will clarify the role of cardiac magnetic resonance in diagnosis, prognosis, and treatment decisions and will facilitate the conception of new imaging‐based guidelines for cardiac involvement in SSc.

Coronary artery ectatic/aneurysmatic disease (CAE/CAA) is a rare but clinically significant condition characterized by abnormal dilatation of the coronary arteries, either diffusely (CAE) or focally (CAA). Its pathophysiology is multifactorial, involving atherosclerosis, genetic predisposition, systemic autoimmunity, and infectious triggers, with distinct etiologies in adults (e.g., atherosclerosis, connective tissue disorders) and children (e.g., Kawasaki disease, multisystem inflammatory syndrome in children). CAE/CAA is associated with increased risks of thrombosis, embolization, and acute coronary syndromes, even in the absence of obstructive coronary artery disease. Diagnostic evaluation relies on multimodality imaging, including transthoracic echocardiography (especially in children), computed tomography coronary angiography, cardiovascular magnetic resonance angiography, and invasive coronary angiography with intravascular ultrasound. Each modality offers unique advantages, but challenges such as radiation exposure, contrast use, expertise and availability persist. Therapeutic management remains empirical due to a lack of randomized trials. In adults, risk factor modification, statins, angiotensin converting enzyme inhibitors / angiotensin receptor blockers, calcium channel blockers are commonly used. Optimal strategies for antiplatelet/anticoagulant treatment are currently under debate. In children, anticoagulation and antiplatelet therapy are recommended for large aneurysms, particularly in Kawasaki disease. Future research should focus on elucidating pathophysiology, comparing imaging modalities, and establishing evidence-based treatment strategies to improve outcomes in this complex patient population.

Lupus myocarditis (LM) is a rare but potentially life threatening manifestation of systemic lupus erythematous (SLE). LM may be rarely the initial presentation of SLE or ma y be presented during the course of the disease. Herein, we report a case of an adult female patient who presented with a 3-day history of abdominal pain, fever and recent onset dyspnea on exertion. Twenty-four hours later the patient developed acute heart failure went into cardiac arrest during her transfer from the internal medicine department to the CT scanner. She was intubated, an intra-aortic balloon pump was inserted, and was transferred to the intensive care unit (ICU). Based on clinical signs, laboratory parameters and cardiac imaging and after the exclusion of other causes of acute heart failure LM was diagnosed. The patient received high doses of corticosteroids and cyclophosphamide and she was improved. The vasopressors were tapered off and the intra-aortic balloon pump was removed. The patient improved and she shifted out of the ICU. The initially increased troponin levels were decreased, while the ejection fraction increased to 60

Various cardiac pathologies such as ischemic/non-ischemic heart disease, valvular heart disease and genetic heart disease may impair cardiac function and lead to heart failure (HF). Each individual condition but also the common endpoint of HF may involve the brain and the immune system next to the heart. The interaction of these systems plays an important role, particularly in the pathogenesis and prognosis of HF, and stress plays a pivotal role in this interaction. The stress system (SS) of the body can be activated by any stress factor exceeding a predefined threshold and all body structures including brain, heart and immune system can be affected. The SS is also responsible for body homeostasis. Both acute and chronic stress may lead to the development of acute and chronic heart disease. Magnetic Resonance Imaging (MRI) is the ideal noninvasive tool without radiation that can provide valuable information about the effect of the SS in various systems/organs using targeted protocols. A holistic approach provided by MRI has the potential to improve our knowledge regarding stress mechanisms on the axis of heart–brain–immune system in HF that may impact effective, individualized treatment. In this review paper, we describe how MRI can be used as a noninvasive tool to assess the effect of stress on the brain–immune system-heart-axis, discussing current possibilities, limitations and future directions.

Background: Inflammatory arthritides (IAs) are systemic inflammatory syndromes that can affect diverse body tissues. Central nervous system involvement has been reported, but is considered rare. We investigated the relationship between cardiac and subclinical brain involvement in patients with IAs. Methods: We consecutively enrolled 25 patients with IAs and 31 as disease controls with non-autoimmune cardiovascular diseases (CVDs) reporting cardiac symptoms. Each participant underwent combined brain/heart magnetic resonance imaging (MRI). We also recruited 25 consecutive asymptomatic healthy controls without CVDs who underwent brain MRI. MRI scans were performed on a 1.5 T system. We investigated cardiac function/tissue characterization and the presence/localization of white matter hyperintensities (WMHs). Results: All groups had similar ages (p = 0.267), and 16 (64%) patients with IAs vs. 7 (23%) disease controls vs. 16 (64%) healthy controls were women (p = 0.001). WMHs were detected in ≥1 brain area in 15 (60%) patients with IAs and 16 (53%) disease controls (p = 0.620). WMHs were significantly less prevalent amongst healthy controls [two (8%)] compared to patients with IAs (p < 0.001). Amongst patients with IAs, an increased cardiac T2 ratio was associated with an increased probability of WMH occurrence [OR per 0.1 unit change (95% CI): 1.29 (1.05–1.59), p = 0.016], while a higher cardiac T2 ratio (per 0.1 unit change) and extracellular volume fraction (ECV) were associated with higher WMH lesion burdens [β (95% CI): 0.12 (0.03–0.20), p = 0.008 and 0.25 (0.00–0.49), p = 0.049, respectively]. Conclusions: Patients with IAs and cardiac symptoms had significantly higher subclinical WMH burdens compared to age/sex-matched healthy controls. Myocardial edema was associated with a greater WMH burden, potentially suggesting shared pathophysiologic substrates.

Myocardial fibrosis constitutes an important pathophysiologic and maladaptive process in the vast majority of cardiac diseases. Contemporary cardiologists are permitted a very nuanced glimpse of myocardial fibrosis by means of cardiovascular magnetic resonance imaging (CMR), and specifically late gadolinium enhancement (LGE) methods. These allow the evaluation of the presence, extent, and distribution of myocardial replacement fibrosis. An increasing amount of scientific evidence has demonstrated a significant role for LGE in the elucidation of cardiac pathophysiologic substrates in patients with autoimmune rheumatic diseases (ARDs) and cardiac involvement. However, whether existing methods for the evaluation of myocardial fibrosis can uniformly be extrapolated for use in patients with ARDs in their present form remains an important question. In this opinion paper, we provide a brief overview of the basic principles underlying LGE imaging, as well as the current status and challenges regarding its use in patients with and without ARDs.

Our purpose was to discuss the advantages and disadvantages of various noninvasive imaging modalities in the evaluation of cardiovascular disease (CVD) in patients with autoimmune rheumatic diseases (ARDs). The detailed knowledge of imaging modalities will facilitate the diagnosis and follow up of CVD in ARDs. Autoimmune Rheumatic Diseases (ARDs) are characterized by alterations in immunoregulatory system of the body. Although there is great progress in anti-rheumatic treatment, ARD patients are still at a higher risk for reduced life expectancy, compared with the general population, which is mainly due to the high incidence of CVD. Cardiovascular imaging holds the promise of early, noninvasive diagnosis and follow up of these patients. Echocardiography (echo), a cost effective, widely available imaging modality, can provide valuable early information about CVD in ARDs and motivate the use of more sophisticated investigations, if needed. Single Photon Emission tomography (SPECT) gives information about myocardial perfusion, while positron emission tomography (PET) gives information about both myocardial perfusion and inflammation with better spatial resolution and less radiation but at a higher financial cost, compared to SPECT. Computed Tomography Coronary Angiography (CTCA) is a reliable tool to rule out the presence of coronary artery disease, which has high incidence in ARD population. Lastly, Cardiovascular Magnetic Resonance (CMR) can perform function and tissue characterization evaluation in the same scan without using radiation and represents the ideal tool for serial evaluation of ARD patients. Lastly, molecular imaging holds the promise for individualized treatment in various ARDs. Cardiovascular imaging is the modern “stethoscope” of the clinicians and therefore they should be familiar with pro and contra of these modalities in order to achieve the best diagnostic and therapeutic target in ARD patients.

Systemic lupus erythematosus (SLE) is a multisystem auto-immune disease that may affect any organ/system, including the cardiovascular system. Several studies have shown that SLE is associated with an increased risk of cardiovascular disease (CVD), even though most of the patients who have lupus are young women. In this review, we present that apart from the traditional risk factors, there are more appropriate SLE-related indices such as imaging parameters, auto-antibodies, disease manifestations, medications, and genetic factors that might represent useful tools to create an algorithm for early identification of SLE patients at increased risk of CVD. Early recognition and appropriate treatment of patients at increased CVD risk might reduce morbidity/mortality and improve the quality of life of patients with SLE.

Systemic sclerosis (SSc) is an autoimmune rheumatic disease, characterized by vascular, inflammatory and fibrotic alterations. Cardiac involvement is the « fatal tip of the iceberg» in SSc, as it leads to high morbidity/mortality. Cardiovascular imaging modalities play an important role in the early diagnosis and treatment assessment of cardiac involvement. Echocardiography is the corner stone for evaluation of cardiac involvement, providing information about function, wall motion, pulmonary pressure, pericardium and valvular disease. It is a low-cost modality, widely available, without radiation and with great experience among cardiologists. However, it is a window and operator dependent modality and cannot provide tissue characterization information, absolutely necessary for diagnosis and treatment of cardiac involvement in SSc. Cardiovascular magnetic resonance (CMR) can perform myocardial function and tissue characterization in the same examination without radiation, has excellent reproducibility and is window and operator independent. The great advantage of CMR is the capability to assess peri- myo-vascular inflammation, myocardial ischemia and presence of replacement and diffuse myocardial fibrosis in parallel with ventricular function assessment. The modified Lake Louise criteria including T2, native T1 mapping and extracellular volume fraction (ECV) has been recently used to diagnose inflammatory cardiomyopathy. According to expert recommendations, myocardial inflammation should be considered if at least 2 indices, one T2 and one T1 parameter are positive, whereas native T1 mapping and ECV assess diffuse fibrosis or oedema, even in the absence of late gadolinium enhancement (LGE). Moreover, transmural/subendocardial LGE following the distribution of coronary arteries and diffuse subendocardial fibrosis not related with epicardial coronary arteries are indicative of epicardial and micro-vascular coronary artery disease, respectively. To conclude, CMR can overcome the limitations of echocardiography by identifying acute/active or chronic myocardial inflammation/fibrosis, ischemia and myocardial infarction using classic and parametric indices in parallel with biventricular function assessment

Cardiac involvement in sickle beta thalassemia (Sβ-thal) patients has been poorly investigated. We aimed to evaluate cardiac function and myocardial iron overload by cardiovascular magnetic resonance (CMR) in patients with Sβ-thal. One-hundred and eleven Sβ-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell anemia (SCA) patients and with 111 gender- and age- matched healthy volunteers. Cine images were acquired to quantify biventricular function. Myocardial iron overload (MIO) was assessed by the T2* technique, while macroscopic myocardial fibrosis was evaluated by the late gadolinium enhancement (LGE) technique. In Sβ-thal and SCA patients, the morphological and functional CMR parameters were not significantly different, except for the left atrial area and left ventricular (LV) stroke volume, indexed by body surface area (p = 0.023 and p = 0.048, respectively), which were significantly higher in SCA patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sβ-thal patients showed significantly higher bi-atrial and biventricular parameters, except for LV ejection fraction, which was significantly lower. The CMR analysis confirmed that Sβ-thal and SCA patients are phenotypically similar. Since Sβ-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sβ-thal/SCA-specific bi-atrial and biventricular reference values.

Atherosclerosis affects patients with systemic immune-mediated inflammatory diseases at an increased rate compared with the general population. In recent years, our understanding of the pathophysiology of atherosclerosis has advanced considerably. Nevertheless, cardiovascular imaging modalities that can adequately assess the biological background of atherosclerosis have not reached widespread clinical adoption. Novel developments in cardiac imaging have the potential to enhance the diagnostic yield of these modalities further while providing essential insights into the anatomy, composition, and biology of atherosclerotic lesions. In this review, we highlight some of the latest developments in the field for the evaluation of atherosclerosis using advances in echocardiography, computed tomography, positron emission tomography, and cardiovascular magnetic resonance. Additionally, we discuss evidence specifically in patients with immune-mediated inflammatory diseases and outline unmet research needs for future development.

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.

The safety of tumor necrosis factor (TNF) inhibitors has been demonstrated for over two decades. However, their effects on cardiovascular function in patients with rheumatic diseases remain controversial, and conclusions are additionally hampered by the cardiovascular complications inherent in such diseases. We present two 15-year-old patients diagnosed with ankylosing spondylitis and juvenile idiopathic arthritis classified as polyarthritis with positive rheumatoid factor, respectively. Soon after treatment onset with adalimumab and etanercept, respectively, they developed myocardial inflammation leading to heart failure. Their condition improved upon treatment discontinuation and onset of secukinumab and tocilizumab, respectively. A thorough literature search revealed that these are the only cases of heart failure reported to date after anti-TNF treatment in adolescents with rheumatic diseases. Although cardiovascular adverse effects seem to be very rare in this population, even atypical symptoms of cardiac failure should not be ignored, and cardiac function should be closely monitored when administering anti-TNF-α.

EDITORIAL article Front. Cardiovasc. Med., 31 January 2024Sec. Cardiovascular Imaging Volume 11 - 2024 | https://doi.org/10.3389/fcvm.2024.1352268

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.