Orthostatic hypotension is associated with higher levels of circulating endostatin.

Aims: The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the relationship between OH and circulating endostatin, an endogenous angiogenesis inhibitor with antitumour effects proposed to be involved in blood pressure (BP) regulation. Methods and results: We compared endostatin levels in 146 patients with OH and 150 controls. A commercial chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin. Linear and multivariate logistic regressions were conducted to test the association between endostatin and OH. Endostatin levels were significantly higher in OH patients (59 024 ± 2513 pg/mL) vs. controls (44 090 ± 1978pg/mL, P < 0.001). A positive linear correlation existed between endostatin and the magnitude of systolic BP decline upon standing (P < 0.001). Using multivariate analysis, endostatin was associated with OH (adjusted odds ratio per 10% increase of endostatin in the whole study population = 1.264, 95% confidence interval 1.141-1.402), regardless of age, sex, prevalent cancer, and cardiovascular disease, as well as traditional cardiovascular risk factors. Conclusion: Circulating endostatin is elevated in patients with OH and may serve as a potential clinical marker of increased cardiovascular risk in patients with OH. Our findings call for external validation. Further research is warranted to clarify the underlying pathophysiological mechanisms.

Thromboembolic and bleeding risk in cardiac amyloidosis.

Cardiac amyloidosis represents a spectrum of conditions characterized by the accumulation of insoluble fibrils, resulting in progressive deposition and myocardial dysfunction. The exact mechanisms contributing to the heightened risk of thromboembolic events and bleeding tendencies in cardiac amyloidosis remain unclear. Proteins such as transthyretin in transthyretin amyloidosis and light chains in light-chain amyloidosis, along with acute phase proteins in amyloid A (AA) amyloidosis, play complex roles in the coagulation cascade, affecting both coagulation initiation and fibrinolysis regulation. The increased occurrence of atrial fibrillation, systolic and diastolic left ventricular dysfunction, and atrial myopathy in patients with cardiac amyloidosis may predispose them to thrombus formation. This predisposition can occur regardless of sinus rhythm status or even with proper anticoagulant management. Bleeding events are often linked to amyloid deposits around blood vessels, which may increase capillary fragility and cause coagulation disturbances, leading to unstable international normalized ratio levels during anticoagulant therapy. Thus, comprehensive risk assessment for both thrombotic and hemorrhagic complications, especially before commencing anticoagulant therapy, is imperative. This review will explore the essential pathophysiological, epidemiologic, and clinical aspects of thromboembolic and bleeding risk in cardiac amyloidosis, evaluating the existing evidence and uncertainties regarding thrombotic and bleeding risk assessment and antithrombotic treatment.

Phosphatase-degradable nanoparticles providing sustained drug release.

AIM: The study aimed to develop enzyme-degradable nanoparticles comprising polyphosphates and metal cations providing sustained release of the antibacterial drug ethacridine (ETH). METHODS: Calcium polyphosphate (Ca-PP), zinc polyphosphate (Zn-PP) and iron polyphosphate nanoparticles (Fe-PP NPs) were prepared by co-precipitation of sodium polyphosphate with cations and ETH. Developed nanocarriers were characterized regarding particle size, PDI, zeta potential, encapsulation efficiency and drug loading. Toxicological profile of nanocarriers was assessed via hemolysis assay and cell viability on human blood erythrocytes and HEK-293 cells, respectively. The enzymatic degradation of NPs was evaluated in presence of alkaline phosphatase (ALP) monitoring the release of monophosphate, shift in zeta potential and particle size as well as drug release. The antibacterial efficacy against Escherichia coli was determined via microdilution assay. RESULTS: NPs were obtained in a size range between 300 - 480 nm displaying negative zeta potential values. Encapsulation efficiency was in the range of 83.73 %- 95.99 %. Hemolysis assay underlined sufficient compatibility of NPs with blood cells, whereas drug and NPs showed a concentration dependent effect on HEK-293 cells viability. Ca- and Zn-PP NPs exhibited remarkable changes in zeta potential, particle size, monophosphate and drug release upon incubation with ALP, compared to Fe-PP NPs showing only minor differences. The released ETH from Ca- and Zn-PP nanocarriers retained the antibacterial activity against E. coli, whereas no antibacterial effect was observed with Fe-PP NPs. CONCLUSION: Polyphosphate nanoparticles cross-linked with divalent cations and ETH hold promise for sustained drug delivery triggered by ALP for parental administration.

Atrial electrofunctional predictors of incident atrial fibrillation in cardiac amyloidosis.

BACKGROUND: Atrial fibrillation (AF) is common in patients with cardiac amyloidosis (CA) and is a significant risk factor for heart failure hospitalization and thromboembolic events. OBJECTIVE: This study was designed to investigate the atrial electrofunctional predictors of incident AF in CA. METHODS: A multicenter, observational study was conducted in 4 CA referral centers including sinus rhythm patients with light-chain (AL) and transthyretin (ATTR) CA undergoing electrocardiography and cardiac magnetic resonance imaging. The primary end point was new-onset AF occurrence. RESULTS: Overall, 96 patients (AL-CA, n = 40; ATTR-CA, n = 56) were enrolled. During an 18-month median follow-up (Q1-Q3, 7-29 months), 30 patients (29%) had incident AF. Compared with those without AF, patients with AF were older (79 vs 73 years; P = .001). They more frequently had ATTR (87% vs 45%; P < .001); electrocardiographic interatrial block (IAB), either partial (47% vs 21%; P = .011) or advanced (17% vs 3%; P = .017); and lower left atrial ejection fraction (LAEF; 29% vs 41%; P = .004). Age (hazard ratio [HR], 1.059; 95% CI, 1.002-1.118; P = .042), any type of IAB (HR, 2.211; 95% CI, 1.03-4.75; P = .041), and LAEF (HR, 0.967; 95% CI, 0.936-0.998; P = .044) emerged as independent predictors of incident AF. Patients exhibiting any type of IAB, LAEF <40%, and age >78 years showed a cumulative incidence for AF of 40% at 12 months. This risk was significantly higher than that carried by 1 (8.5%) or none (7.6%) of these 3 risk factors. CONCLUSION: In patients with CA, older age, IAB on 12-lead electrocardiography, and reduced LAEF on cardiac magnetic resonance imaging are significant and independent predictors of incident AF. A closer screening for AF is advisable in CA patients carrying these features.

Left Atrial Strain to Predict Postoperative Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery being associated with poorer outcomes. Revealing before the operation of left atrial subtle structural/functional abnormalities may help to identify patients at increased risk of POAF. We investigated the role of left atrial strain parameters by preoperative speckle tracking echocardiography as independent predictors of POAF in patients undergoing coronary artery bypass graft. METHODS: Consecutive patients undergoing isolated coronary artery bypass graft were prospectively enrolled at three Italian centers. All patients underwent transthoracic echocardiography before the operation. The occurrence of POAF up to discharge was monitored. RESULTS: Overall, a total of 310 patients were included. POAF was demonstrated in 103 patients (33%). At receiver operating characteristic curve analysis, lower global peak atrial longitudinal strain (PALS) values significantly predicted the risk of POAF (area under the curve, 0.74; P<0.001). The optimal cutoff value for the arrhythmia prediction was a global PALS value <28%, with a specificity of 86% and a sensitivity of 36%. The incidence of POAF was 51% in patients with global PALS <28% versus 14% in those with PALS ≥28% (P<0.001), with a POAF-free survival at Kaplan-Meier analysis of 45.4% and 85.7%, respectively (P<0.001). At multivariate analysis, a global PALS <28% carried a 3.6-fold higher risk of POAF (hazard ratio, 3.6 [95% CI, 2.2-5.9]; P<0.001). The risk increase was even higher when PALS <28% was associated with age ≥70 years (adjusted hazard ratio, 11.2 [4.7-26.6], P<0.001). CONCLUSIONS: A presurgery global PALS <28% is a specific parameter to stratify patients at increased risk of POAF after coronary artery bypass graft. This assessment can be useful to identify patients at higher arrhythmic risk in whom perioperative preventive strategies and stricter monitoring aimed at early diagnosing and treating POAF may be applied.

Surgical management of atrial fibrillation in patients undergoing cardiac surgery: a systematic review of clinical practice guidelines and recommendations.

AIMS: Surgical ablation of atrial fibrillation (AF) has been demonstrated to be a safe procedure conducted concomitantly alongside cardiac surgery. However, there are conflicting guideline recommendations surrounding indications for surgical ablation. We conducted a systematic review of current recommendations on concomitant surgical AF ablation. METHODS AND RESULTS: We identified publications from MEDLINE and EMBASE between January 2011 and December 2022 and additionally searched Guideline libraries and websites of relevant organizations in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 895 studies screened, 4 were rigorously developed (AGREE-II > 50%) and included. All guidelines agreed on the definitions of paroxysmal, persistent, and longstanding AF based on duration and refraction to current treatment modalities. In the Australia-New Zealand (CSANZ) and European (EACTS) guidelines, opportunistic screening for patients >65 years is recommended. The EACTS recommends systematic screening for those aged >75 or at high stroke risk (Class IIa, Level B). However, this was not recommended by American Heart Association or Society of Thoracic Surgeons guidelines. All guidelines identified surgical AF ablation during concomitant cardiac surgery as safe and recommended for consideration by a Heart Team with notable variation in recommendation strength and the specific indication (three guidelines fail to specify any indication for surgery). Only the STS recommended left atrial appendage occlusion (LAAO) alongside surgical ablation (Class IIa, Level C). CONCLUSION: Disagreements exist in recommendations for specific indications for concomitant AF ablation and LAAO, with the decision subject to Heart Team assessment. Further evidence is needed to develop recommendations for specific indications for concomitant AF procedures and guidelines need to be made congruent.

Power-Up for Mucoadhesiveness: Two Generations of Thiolated Surfactants for Enhanced Sticky Nanoemulsions.

Nanoemulsions can be tuned toward enhanced gastro-intestinal retention time by incorporating thiolated surfactants into their surface. Tailoring the chemical reactivity of the thiol headgroup has major influence on mucoadhesive features of the nanoemulsion. Two generations of thiolated surfactants were synthetically derived from PEG-40-stearate featuring either a free thiol group or an S-protected thiol group. The surfactants were characterized regarding critical micelle concentration (CMC), hemolytic activity, and cytotoxicity. Subsequently, they were incorporated into nanoemulsions and the resulting nanoemulsions were characterized regarding particle size, polydispersity index (PDI), zeta potential, and time-dependent stability. Afterward, mucosal interactions as well as mucoadhesion on porcine intestinal mucosa were investigated. Successful synthesis of Cysteine-PEG-40-stearate (CYS-PEG-40-stearate) and MNA-Cysteine-PEG-40-stearate (MNA-CYS-PEG-40-stearate) was confirmed by 1H NMR spectroscopy. Both chemical modifications led to slightly elevated CMC values while preserving low cytotoxicity and hemotoxicity. Incorporation into nanoemulsions had minor influence on overall physical particle characteristics, while interactions with mucus and mucoadhesiveness of the nanoemulsions were drastically improved resulting in the rank order PEG-40-stearate < CYS-PEG-40-stearate < MNA-CYS-PEG-40-stearate. Accordingly, thiolated surfactants, especially S-protected derivatives, are versatile tools to generate highly mucoadhesive nanoemulsions.

Common Clinical and Molecular Pathways between Migraine and Sarcoidosis.

Migraine and sarcoidosis are two distinct medical conditions that may have some common biological and clinical pathways. Sarcoidosis is a chronic granulomatous disease characterized by the formation of granulomas in various organs, including the lungs, skin, cardiovascular system, lymph nodes, and brain. Migraine is a common comorbidity in sarcoidosis patients and a common neurological disorder characterized by recurrent headaches that can be accompanied by other symptoms, such as nausea, vomiting, and sensitivity to light and sound. There have been several reports of individuals with neurosarcoidosis experiencing migraines, though the exact relationship between the two disorders is not well understood. Both conditions have been associated with inflammation and the activation of the immune system. In sarcoidosis, the formation of granulomas is thought to be an immune response to the presence of an unknown antigen. Similarly, the pain and other symptoms associated with migraines are thought to be caused by inflammation in the brain and the surrounding blood vessels. There is also evidence to suggest an interplay of environmental and genetic factors playing a role in both conditions, but evidence is inconsistent with the hypothesis of shared genetic susceptibility. This review aims to illustrate common clinical and biological pathways between migraine and sarcoidosis, including inflammation and dysregulation of the immune system, with a focus on the cumulative burden of concurrent disorders and therapeutic implications.

An acute increase in Left Atrial volume and left ventricular filling pressure during Adenosine administered myocardial hyperaemia: CMR First-Pass Perfusion Study.

OBJECTIVE: To investigate whether left atrial (LA) volume and left ventricular filling pressure (LVFP) assessed by cardiovascular magnetic resonance (CMR) change during adenosine delivered myocardial hyperaemia as part of a first-pass stress perfusion study. METHODS AND RESULTS: We enrolled 33 patients who had stress CMR. These patients had a baseline four-chamber cine and stress four-chamber cine, which was done at peak myocardial hyperaemic state after administering adenosine. The left and right atria were segmented in the end ventricular diastolic and systolic phases. Short-axis cine stack was segmented for ventricular functional assessment. At peak hyperaemic state, left atrial end ventricular systolic volume just before mitral valve opening increased significantly from baseline in all (91 ± 35ml vs. 81 ± 33ml, P = 0.0002), in males only (99 ± 35ml vs. 88 ± 33ml, P = 0.002) and females only (70 ± 26ml vs. 62 ± 22ml, P = 0.02). The right atrial end ventricular systolic volume increased less significantly from baseline (68 ± 21ml vs. 63 ± 20ml, P = 0.0448). CMR-derived LVFP (equivalent to pulmonary capillary wedge pressure) increased significantly at the peak hyperaemic state in all (15.1 ± 2.9mmHg vs. 14.4 ± 2.8mmHg, P = 0.0002), females only (12.9 ± 2.1mmHg vs. 12.3 ± 1.9mmHg, P = 0.029) and males only (15.9 ± 2.8mmHg vs. 15.2 ± 2.7mmHg, P = 0.002) cohorts. CONCLUSION: Left atrial volume assessment by CMR can measure acute and dynamic changes in preloading conditions on the left ventricle. During adenosine administered first-pass perfusion CMR, left atrial volume and LVFP rise significantly.

Clinical and Cardiovascular Magnetic Resonance Imaging Features of Cardiac Amyloidosis.

Amyloidosis is a systemic disease characterized by the accumulation of insoluble aggregates in various organs, leading to parenchymal damage. When these amyloid fibrils are deposited in the extracellular matrix of the cardiac structures, the condition is referred to as cardiac amyloidosis (CA). The extent of organ involvement determines the degree of cardiac impairment, which can significantly impact prognosis. The two most implicated proteins in CA are transthyretin and misfolded monoclonal immunoglobulin light chains. These proteins give rise to two distinct clinical forms of CA: transthyretin amyloidosis (ATTR-CA) and light-chain amyloidosis (AL-CA). ATTR-CA is further classified into two subtypes: ATTRm-CA, which occurs at a younger age and is caused by hereditary misfolded mutated proteins, and ATTRwt-CA, which is an acquired wild-type form more commonly observed in older adults, referred to as senile amyloidosis. While AL-CA was considered the most prevalent form for many years, recent autopsy studies have revealed an increase in cases of ATTRwt-CA. This narrative review aims to describe the clinical and imaging features of CA, with a particular focus on cardiac complications and mortality associated with the AL form. Early identification and differentiation of CA from other disorders are crucial, given the higher risk and severity of cardiac involvement in AL-CA. Furthermore, emphasis is placed on the potential utility of cardiovascular magnetic resonance imaging in detecting early cases of CA.

Sarcoidosis and COVID-19: At the Cross-Road between Immunopathology and Clinical Manifestation.

Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of the immune system featuring inappropriate immune responses, exacerbation of inflammatory responses, and multiple organ dysfunction syndrome in patients with severe disease. Sarcoidosis, also known as Besnier-Boeck-Schaumann disease, is an idiopathic granulomatous multisystem disease characterized by dense epithelioid non-necrotizing lesions with varying degrees of lymphocytic inflammation. These two diseases have similar clinical manifestations and may influence each other at multiple levels, eventually affecting their clinical courses and prognosis. Notably, sarcoidosis patients are at high risk of severe COVID-19 pneumonia because of the underlying lung disease and chronic immunosuppressive treatment. In this narrative review, we will discuss interactions between sarcoidosis and COVID-19 in terms of clinical manifestations, treatment, and pathogenesis, including the role of the dysregulated renin-angiotensin system, altered immune responses involving increased cytokine levels and immune system hyperactivation, and cellular death pathways.

Clinical applications of heart rhythm monitoring tools in symptomatic patients and for screening in high-risk groups.

Recent technological advances have facilitated and diversified the options available for the diagnosis of cardiac arrhythmias. Ranging from simple resting or exercise electrocardiograms to more sophisticated and expensive smartphones and implantable cardiac monitors. These tests and devices may be used for varying periods of time depending on symptom frequency. The choice of the most appropriate heart rhythm test should be guided by clinical evaluation and optimized following accurate characterization of underlying symptoms, 'red flags', risk factors, and consideration of cost-effectiveness of the different tests. This review provides evidence-based guidance for assessing suspected arrhythmia in patients who present with symptoms or in the context of screening, such as atrial fibrillation or advanced conduction disturbances following transcatheter aortic valve implantation in high-risk groups. This is intended to help clinicians choose the most appropriate diagnostic tool to facilitate the management of patients with suspected arrhythmias.

Chitosan/sulfobutylether-ß-cyclodextrin based nanoparticles coated with thiolated hyaluronic acid for indomethacin ophthalmic delivery.

Indomethacin (IND) is topically administered for the treatment of the anterior segment diseases such as conjunctivitis, uveitis, and inflammation prevention for post-cataract surgery, as well as posterior segment diseases as macular edema. Currently IND is available as 0.1% w/v hydroxypropyl-ß-cyclodextrin-based eye drop formulation and its bioavailability is limited by several drawbacks such as the nasolacrimal duct draining, the reflex blinking and the low volume of the conjunctival sac. In this study, chitosan (CS)/sulfobutylether-ß-cyclodextrin (SBE-ß-CD) based nanoparticles (NPs) with a mean diameter of 340 (±7) nm, a ζ-potential value of +18.3 (±0.5) mV and coated with thiolated low molecular weight hyaluronic acid were formulated to improve both the solubility and the residential time in the conjunctival sac of the loaded drug IND. The NPs were prepared through the ionotropic gelation technique, exploiting the interaction between the positively charged amino group of CS and the negatively charged sulfonic group of SBE-ß-CD. The mucoadhesive properties of the NPs were evaluated on chicken trachea and esophagus tissues using a texture analyser. The irritability effects of NPs were disclaimed with Hecam test. The developed coated NPs showed increased residential time in the conjunctival sac, displayed no irritancy or toxicity for local administration, making them an optimal and innovative drug delivery system for the treatment of anterior segment inflammation diseases. On the other hand, the uncoated NPs displayed better permeating properties since they are smaller and could be further exploited for the treatment of posterior segment diseases.

Magnetic Resonance for Differential Diagnosis of Left Ventricular Hypertrophy: Diagnostic and Prognostic Implications.

BACKGROUND: Left ventricular hypertrophy (LVH) may be due to different causes, ranging from benign secondary forms to severe cardiomyopathies. Transthoracic Echocardiography (TTE) and ECG are the first-level examinations for LVH diagnosis. Cardiac magnetic resonance (CMR) accurately defines LVH type, extent and severity. OBJECTIVES: to evaluate the diagnostic and prognostic role of CMR in patients with TTE and/or ECG evidence of LVH. METHODS: We performed CMR in 300 consecutive patients with echocardiographic and/or ECG signs of LVH. RESULTS: Overall, 275 patients had TTE evidence of LVH, with initial suspicion of hypertrophic cardiomyopathy (HCM) in 132 (44%), cardiac amyloidosis in 41 (14%), hypertensive LVH in 48 (16%), aortic stenosis in 4 (1%), and undetermined LVH in 50 (16%). The initial echocardiographic diagnostic suspicion of LVH was confirmed in 172 patients (57.3%) and changed in 128 patients (42.7%, p < 0.0001): the diagnosis of HCM increased from 44% to 71% of patients; hypertensive and undetermined LVH decreased significantly (respectively to 4% and 5%). CMR allowed for a diagnosis in 41 out of 50 (82%) patients with undetermined LVH at TTE. CMR also identified HCM in 17 out of 25 patients with apparently normal echocardiography but with ECG criteria for LVH. Finally, the reclassification of the diagnosis by CMR was associated with a change in survival risk of patients: after CMR reclassification, no events occurred in patients with undetermined or hypertensive LVH. CONCLUSIONS: CMR changed echocardiographic suspicion in almost half of patients with LVH. In the subgroup of patients with abnormal ECG, CMR identified LVH (particularly HCM) in 80% of patients. This study highlights the indication of CMR to better characterize the type, extent and severity of LVH detected at echocardiography and suspected with ECG.

Aortic regurgitation management: a systematic review of clinical practice guidelines and recommendations.

Guidelines for the diagnosis and management of aortic regurgitation (AR) contain recommendations that do not always match. We systematically reviewed clinical practice guidelines and summarized similarities and differences in the recommendations as well as gaps in evidence on the management of AR. We searched MEDLINE and Embase (1 January 2011 to 1 September 2021), Google Scholar, and websites of relevant organizations for contemporary guidelines that were rigorously developed as assessed by the Appraisal of Guidelines for Research and Evaluation II tool. Three guidelines met our inclusion criteria. There was consensus on the definition of severe AR and use of echocardiography and of multimodality imaging for diagnosis, with emphasis on comprehensive assessment by the heart valve team to assess suitability and choice of intervention. Surgery is indicated in all symptomatic patients and aortic valve replacement is the cornerstone of treatment. There is consistency in the frequency of follow-up of patients, and safety of non-cardiac surgery in patients without indications for surgery. Discrepancies exist in recommendations for 3D imaging and the use of global longitudinal strain and biomarkers. Cut-offs for left ventricular ejection fraction and size for recommending surgery in severe asymptomatic AR also vary. There are no specific AR cut-offs for high-risk surgery and the role of percutaneous intervention is yet undefined. Recommendations on the treatment of mixed valvular disease are sparse and lack robust prospective data.

Tricuspid regurgitation management: a systematic review of clinical practice guidelines and recommendations.

Tricuspid regurgitation (TR) is a highly prevalent condition and an independent risk factor for adverse outcomes. Multiple clinical guidelines exist for the diagnosis and management of TR, but the recommendations may sometimes vary. We systematically reviewed high-quality guidelines with a specific focus on areas of agreement, disagreement, and gaps in evidence. We searched MEDLINE and EMBASE (1 January 2011 to 30 August 2021), the Guidelines International Network International, Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, Google Scholar, and websites of relevant organizations for contemporary guidelines that were rigorously developed (as assessed by the Appraisal of Guidelines for Research and Evaluation II tool). Three guidelines were finally retained. There was consensus on a TR grading system, recognition of isolated functional TR associated with atrial fibrillation, and indications for valve surgery in symptomatic vs. asymptomatic patients, primary vs. secondary TR, and isolated TR forms. Discrepancies exist in the role of biomarkers, complementary multimodality imaging, exercise echocardiography, and cardiopulmonary exercise testing for risk stratification and clinical decision-making of progressive TR and asymptomatic severe TR, management of atrial functional TR, and choice of transcatheter tricuspid valve intervention (TTVI). Risk-based thresholds for quantitative TR grading, robust risk score models for TR surgery, surveillance intervals, population-based screening programmes, TTVI indications, and consensus on endpoint definitions are lacking.

Clinical Features and Diagnosis of Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is an unusual, but potentially harmful, manifestation of systemic sarcoidosis (SA), a chronic disease characterized by organ involvement from noncaseating and nonnecrotizing granulomas. Lungs and intrathoracic lymph nodes are usually the sites that are most frequently affected, but no organ is spared and CS can affect a variable portion of SA patients, up to 25% from post-mortem studies. The cardiovascular involvement is usually associated with a bad prognosis and is responsible for the major cause of death and complications, particularly in African American patients. Furthermore, the diagnosis is often complicated by the occurrence of non-specific clinical manifestations, which can mimic the effect of more common heart disorders, and imaging and biopsies are the most valid approach to avoid misdiagnosis. This narrative review summarizes the main clinical features of CS and imaging findings, particularly of CMR and 18-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) that can give the best cost/benefit ratio in terms of the diagnostic approach. Imaging can be very useful in replacing the endomyocardial biopsy in selected cases, to avoid unnecessary, and potentially dangerous, invasive maneuvers.