Cardiac amyloidosis is increasingly recognized as an underlying cause of left ventricular wall thickening, heart failure, and arrhythmia with variable clinical presentation. Due to the subtle cardiac findings in early transthyretin cardiac amyloidosis and the availability of therapies that can modify but not reverse the disease progression, early recognition is vital. In light chain amyloidosis, timely diagnosis and treatment can significantly improve survival. In this manuscript, we review the clinical, imaging, and electrocardiographic clues that should raise suspicion for cardiac amyloidosis and provide a simplified diagnostic workup algorithm that ensures an accurate diagnosis. The evolution of the noninvasive diagnosis of cardiac amyloidosis has significantly influenced our understanding of disease prevalence, presentations, and outcomes. However, clinical recognition of clues and red flags remains the most important factor in advancing the care of patients with cardiac amyloidosis. In this review, we discuss the clinical clues that should raise suspicion for cardiac amyloidosis (CA) in patients presenting in outpatient settings, and we provide a patient-centered diagnostic workup that ensures an accurate diagnosis .Systemic amyloidosis is caused by the extracellular deposition of misfolded protein in multiple organs and systems. The two most prevalent amyloid types with common cardiac involvement are immunoglobulin light chain and transthyretin (ATTR) amyloidosis. These can overlap in presentation but differ in diagnostic pathway and therapeutic approaches2 AL-CA is relatively uncommon, with an incidence of 3 to 9 per million person-years.3 Across all forms of amyloidosis, misfolded proteins are often more prevalent in older individuals, possibly due to the changes in physiological microenvironments seen with aging.1 The age at diagnosis varies, although the mean age of AL-CA diagnosis is approximately 57 years old.5 AL-CA is historically more readily recognized compared to ATTR, often with a wide-ranging presentation depending on which organ is involved. Symptoms may include heart failure, weight loss, nephrotic syndrome, macroglossia, and GI disturbances, among others.6Light chain amyloidosis (AL-CA) is caused by sporadic deposition of kappa or lambda light chains in tissue and therefore does not follow any known inheritance pattern. The disease is one of the plasma cell dyscrasias and found in 10% of patients with multiple myeloma.7 ATTR amyloidosis can result from an amino acid change, leading to variants (ATTRv) that precipitate transthyretin tetramer instability, or can occur despite having normal protein structure, as in wild type ATTR (ATTRwt).8 These two types are closely related in pathophysiology, both showing deposition of fibrils in different organs and systems, but the distinction comes in their presentation and currently available therapies.Transthyretin is a thyroxine and retinol transport protein predominantly produced in the liver, choroid plexus, and retina and is found circulating in plasma and cervical spinal fluid.9 ATTRwt predominantly presents as heart failure with features of restrictive and infiltrative cardiomyopathy, with additional history clues including orthopedic manifestations such as prior carpal tunnel release, spinal stenosis, and neuropathy.10 ATTRv is inherited through an autosomal dominant pattern with over 100 different associated variants.11 The severity, age of onset, and symptomology of the disease is dependent on the particular variant and geographical location.12 In ATTRv, early onset is considered before the age of 50, and incidence varies geographically in endemic versus nonendemic areas.14 In the United States, there is a higher prevalence of the p.Val142Ile mutation among people of African and Afro-Caribbean ancestry but with variable penetrance.15 This mutation is of particular interest given its prevalence and predominantly cardiac phenotype.17 Overall, ATTRv has a rather heterogeneous presentation depending on the underlying variant and can emerge with a polyneuropathy phenotype, cardiomyopathy phenotype, or mixed.18As the name suggests, ATTRwt is a sporadic disease of older individuals, most often seen in White males, with prevalence increasing significantly (12-25%) in people over 80 years.Table 1 summarizes extracardiac symptoms and disease manifestations that should alert the clinician to consider amyloidosis in the differential.21Due to the varying and at times nonspecific symptomatology in patients with amyloidosis, it is important to pay attention to minor clues in a patient’s history, such as previous orthopedic or neurological conditions that were present years prior to presentation, and carefully evaluate left ventricular hypertrophy (LVH) even in the presence of hypertension. 22 The cardiac phenotype typically starts with subclinical extracellular deposition of amyloid fibrils, with progressive increase in ventricular wall thickness, atrial dilatation, arrhythmias, and conduction system abnormalities.23 The cardiac phenotype is the leading cause of mortality, with varying survival rates depending on the stage of cardiac involvement.24 For example, in untreated advanced AL-CA, the mean survival is less than 6 months after development of heart failure.25 Early recognition of cardiac involvement in amyloidosis is vital given the high morbidity and mortality coupled with therapeutics that frequently halt the progression of disease but do not reverse it.22In the cardiac phenotype, amyloidosis can cause a wide range of presentations; however, the classic presentation is often cardiomyopathy with restrictive hemodynamics and heart failure.Table 2 provides some clues from cardiac involvement in amyloidosis.32Perhaps the most important aspect is developing a systematic approach to evaluating systemic signs, symptoms, and diagnostic findings that could provide clues to the diagnosis, which, in the era of electronic medical record systems, can be integrated as a systematic checklist for every new patient with heart failure. 34 A history of hypertension should not discourage such an evaluation since hypertension is common in patients with a history of ATTR.35 Once clinical suspicion is raised, pretest probability should drive targeted evaluation.While the sensitivity and specificity of electrocardiograms for cardiac amyloidosis diagnosis is low, the combination of red flags from the patient’s history and electrocardiogram, in the setting of LV hypertrophy, should prompt an evaluation for cardiac amyloidosis.36 The coexistence of these conditions represents a unique challenge since AS can also lead to increased LV wall thickness and abnormal strain pattern. However, this also represents a unique opportunity to apply screening for red flags in patients presenting with AS, akin to those presenting with heart failure, to identify those with underlying ATTR-CM (Table 2). This is especially important given the comparable mortality between AS patients who underwent transcatheter aortic valve replacement (TAVR) and patients with AS and ATTR-CM who underwent TAVR without other treatments for ATTR-CM.37 Nitsche et al. recently reported on a clinical risk score that can be used to identify ATTR-CM by narrowing down red flags, which include carpal tunnel syndrome, right bundle branch block, ≥ 85 years of age, elevated high sensitivity troponin T ≥ 20 ng/L, having an interventricular septum thickness ≥ 18 mm, E/A ratio ≥ 1.4, and, when feasible to perform, a Sokolow index < 1.9 millivolt.38 Ultimately, the message is to recognize that ATTR-CM coexists with AS, and an evaluation for ATTR-CM red flags in all patients with AS is necessary to improve the care of such patients, especially given the availability of therapeutics.Coexistent aortic stenosis (AS) and ATTR cardiomyopathy (ATTR-CM) is a relatively recent finding, and there are no mechanistic studies to directly explain the high prevalence of ATTR-CM in AS.40 These markers, in addition to glomerular filtration rate, are the backbone of prognostic models in both AL-CA and ATTR-CM.44Currently, no single laboratory test can definitively rule in or out cardiac amyloidosis. When used within the clinical context, elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in patients with stable symptoms in the nonacute setting can be a red flag when it is discrepant with New York Heart Association (NYHA) class. Similarly, chronically elevated troponin is a marker of subclinical myocardial injury and, in the absence of other explanation, should prompt workup for amyloidosis in the presence of LVH.46 Local teams should work with their respective labs to ensure that direct immunofixation is performed on all samples, irrespective of the results of protein electrophoresis, rather than only as a reflex immunofixation to samples with abnormal protein electrophoresis. It should be noted that patients with ATTR-CM have a high prevalence of monoclonal gammopathy of undetermined significance , and this should prompt careful evaluation in conjunction with a hematologist to rule out AL-CA and risk stratify MGUS.48 Light chains are renally cleared, and in the setting of chronic kidney disease, both kappa and lambda light chain levels are elevated (kappa > lambda), which led to the introduction of a “renal” free light chain ratio to account for alterations in renal clearance in these patients.51 Given the complexities of patients presenting with CA, a granular evaluation of these patients is still indicated.Additionally, with the overlap between AL and ATTR presentation, it is important to rule out AL-CA via laboratory studies early in the evaluation, although at times, for practicality purposes, ruling out AL and obtaining technetium-99m pyrophosphate (Tc-99m PYP) scintigraphy occur simultaneously. All patients with CA phenotype should undergo direct serum and urine immunofixation electrophoresis and light chain quantification to screen for AL-CA with a > 95% sensitivity.53 Additionally, retinol binding protein 4, which binds to the transthyretin tetramer, has shown diagnostic potential when combined with additional clinical factors in identifying p.Val142Ile ATTRv-CM.54In ATTR-CM, transthyretin  levels can be useful for risk stratification and show early promise for assessing treatment response in patients on tafamidis.55The two most common imaging modalities used after echocardiography in the workup of LVH are cardiac magnetic resonance imaging (CMR) and bone scintigraphy . CMR can be viewed as part of the routine workup of patients with LVH or can be specifically used in the workup of patients with suspected CA. Pretest probability should guide which imaging test to pursue after echocardiography. In patients who have undifferentiated LVH or appear to be at low to intermediate suspicion of CA, CMR is the appropriate next step in evaluating LVH. In patients who have clear high pretest probability for ATTR-CM based on clinical and echocardiographic evaluation, bone scintigraphy is used to confirm ATTR-CM after ruling out AL amyloid cardiomyopathy.56 Aside from the typical features that can be seen, two main CMR sequences provide diagnostic and mechanistic understanding into the underlying burden of disease.CMR provides a wealth of cardiac data including anatomy, function, and tissue characterization, with the constellation of findings being highly sensitive and specific for detecting CA.57 The presence and pattern of LGE provides important diagnostic clues to the extent of CA. The main LGE patterns are diffuse subendocardial LGE and transmural LGE. A common issue when performing LGE imaging is abnormal gadolinium kinetics, where the myocardium and blood T1 values are similar because of high myocardial uptake and fast blood pool washout, which makes it harder to null the myocardium for acquisition of phase-sensitive inversion recovery sequences.58 Although abnormal gadolinium kinetics can provide diagnostic clues, it can cause confusion in interpreting the images due to poor LGE technique . Routine use of native T1 mapping and extracellular volume (ECV) quantification can rescue these shortcomings .In amyloidosis, LGE is reflective of amyloid fibrils occupying the extracellular space and the associated subendocardial fibrosis.59 ECV, which requires both native and post-gadolinium T1 map, can also be used as a surrogate for total amyloid mass in the myocardium.60 Rarely, certain early amyloidosis phenotypes, especially in patients with hereditary ATTR, can present without significant LVH and with minimal or absent LGE but with elevated T1 mapping and ECV . Hence, one should always attempt to acquire these sequences in patients referred with LVH or suspicion for CA.Progressive amyloid fiber deposition leads to progressive expansion of the extracellular space, which can be estimated using CMR. Native T1 mapping can offer clues regarding the presence of CA without using gadolinium.61It is worth noting that CMR cannot differentiate between subtypes of CA. Based on the recent multisocietal expert consensus recommendations for multimodality imaging in CA, typical imaging findings of CA on CMR should be accompanied by either histological confirmation (cardiac or extra-cardiac) or by bone scintigraphy and laboratory studies for AL-CA.62 While planar imaging has been historically used, recent advances have shown how myocardial single-photon emission computed tomography (SPECT) imaging is essential to define myocardial involvement and exclude false positive scans due to blood pooling of the tracer.65 In addition, SPECT/computed tomography in particular provides excellent anatomical landmarks that help differentiate blood pooling versus myocardial uptake in milder and regional forms of tracer uptake.66 Despite its limitations, in a population with a high clinical pre-test probability for ATTR-CM, grades 2 to 3 on planar imaging combined with a negative serum evaluation for AL-CA yield a 100% positive predictive value.55 The use of Tc-99m PYP with SPECT can be a successful strategy in making a nontissue diagnosis of ATTR-CM when clear diffuse uptake of the tracer is present. In all other atypical imaging findings, supportive evidence should be sought from other imaging tests or tissue biopsy to avoid misdiagnosis of ATTR-CM.The resurrection of Tc-99m PYP scintigraphy and a subsequent multicenter study in 2016 have revolutionized the approach to diagnosing ATTR-CM.67Historically, endomyocardial biopsy was required to diagnose and subtype cardiac amyloidosis. With advances in diagnostic imaging and evaluation of CA, endomyocardial biopsy is not required routinely for ATTR-CM patients. Biopsy in ATTR-CM is indicated in the following cases: (1) when one cannot reliably differentiate between AL and ATTR-CM, such as abnormal monoclonal protein workup in elderly individuals who are at risk for ATTR-CM or in conjunction with abnormal bone scintigraphy; (2) when imaging has atypical findings, such as borderline or negative nuclear scintigraphy in suspected patients with ATTR-CM; or (3) to evaluate for other less common forms of amyloidosis. In AL-CA, endomyocardial biopsy is more frequently required in the absence of histological confirmation from an extra-cardiac site. The demonstration of Congo red stained extracellular amorphous material in the presence of an amyloid clinical phenotype is diagnostic of the disease, with mass spectroscopy providing unique capabilities of subtyping the amyloid protein.69 If a patient is genotype positive for a pathogenic variant, it is vital to provide genetic counseling and assess family members either for the phenotype or via cascade genetic screening. ATTRv has an autosomal dominant inheritance pattern that is age dependent with variable penetrance.11 Each pathogenic variant has its own unique biochemical effects and phenotype. Generally, it is recommended to start genetic testing at least 10 years prior to the onset of clinical disease in a family member or earlier if signs of clinical disease appear.1In patients deemed to have ATTR-CM, transthyretin gene sequencing is essential to differentiate ATTRv-CM from ATTRwt-CM. It is vital to differentiate between the two subtypes because there are implications with regard to understanding disease severity, family screening, and utilization of approved therapies.Cardiac amyloidosis, particularly ATTR-CM, is common in elderly patients with heart failure. Red flags exist and can be systematically incorporated into one’s own practice as simple screening tools to improve the pretest probability. It is essential to differentiate ATTR-CM from AL-CA given the vastly different treatment approach. As the noninvasive diagnosis of CA continues to evolve, improvement in the diagnosis rate of ATTR-CM with less reliance on endomyocardial biopsy as well as availability of novel therapeutics promise a better future for patients living with ATTR-CM.Transthyretin cardiac amyloidosis (CA) is a common cause of heart failure in elderly patients. Enhancing pretest probability by clinical screening of red flags improves diagnostic yield of testing.Transthyretin amyloid cardiomyopathy coexists with aortic stenosis.Light chain amyloidosis should be ruled out in all patients with CA phenotype using serum free light chain assay and direct serum and urine immunofixation electrophoresis.A modern approach to the noninvasive diagnosis of transthyretin CA using bone scintigraphy requires imaging with single-photon emission computed tomography.Cardiac magnetic resonance imaging has diverse roles in the imaging cascade of patients with left ventricular hypertrophy including CA.Houston Methodist is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.Houston Methodist designates this enduring material for a maximum of .25 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.https://cvent.me/0KEEPx.Click to earn CME credit:


Ischemic heart disease (IHD), also known as coronary artery disease (CAD), is a leading cause of morbidity and mortality in adults. The aims of this research were to study the recent advances on the prognostic and diagnostic value, drawbacks, and the future directions of cardiac magnetic resonance imaging (CMRI) in the diagnosis of IHD. One hundred patients with IHD who had been clinically diagnosed were enrolled in this study prospectively. CMRI; Siemens Magnetom Sola 1.5 T MRI scanner was used to examine the patients. To confirm the diagnosis, conventional coronary angiography was used. CMRI revealed that the left ventricular (LV) volumes and systolic function of male and female patients differed by age decile were 28.9 ± 3.5%; 32 ± 1.7%, 53.3 ± 11.2; 58 ± 6.6 ml, 100.6 ± 7.1; 98.3 ± 14.7 bpm, 5.4 ± 1.4; 5.8 ± 1.5 L/min, 189 ± 14.3; 180 ± 10.9 ml, and 136 ± 3.1; 123 ± 4.4 ml for the left ventricle ejection fraction (LVEF), stroke volume (SV), heart rate, cardiac output, end diastolic volume (EDV), and end systolic volume (ESV), respectively. CMRI has sensitivity, specificity, and accuracy of 97%, 33.33%, and 95.15%, respectively. Finally, CMRI provides a comprehensive assessment of LV function, myocardial perfusion, and viability, as well as coronary anatomy. As a result, the purpose of this study was to investigate the utility of cardiac magnetic resonance imaging (CMRI) as a diagnostic tool for IHD. This study's specific objectives are to update the reader on the current state of CMRI, with a special emphasis on the basic CMR sequences in IHD. Recent advances in the prognostic and diagnostic value of CMR in the evaluation of IHD are also discussed. Furthermore, the limitations of CMRI in the evaluation of IHD in the study samples will be presented in this study.Ischemic heart disease (IHD), also known as coronary artery disease (CAD), can be accurately diagnosed with advanced radio-diagnostic techniques such as cardiac catheterization and computed tomography cardiac angiography (CTCA). However, such applications are associated with a number of limitations that have an impact on patient safety and the accuracy of diagnoses. The problem with both cardiac catheterization and CTCA is that the patient is exposed to a high radiation dose during the procedure. As a result, using cardiac magnetic resonance (CMR) technologies to overcome such issues is extremely beneficial to the patientOne hundred patients with IHD were enrolled prospectively in this study after providing informed written and verbal consent from a local ethics committee at the Radiology and Medical Imaging Department, King Fahad Medical City (KFMC), Riyadh-Saudi Arabia, that was obtained prior to the study's start. Informed consent was obtained from parents or legal guardians of participants who are under the age of 18. The local ethics committee (LEC) of the College of Medical Radiological Sciences (CMRS), Sudan University of Science and Technology, Khartoum, Sudan approved study . The ethics procedures used were in accordance with the 1975 Helsinki Declaration, which was updated in 2013. Patients who had been clinically examined by a referring cardiologist and were scheduled for CMRI and conventional coronary angiography were included in the study after their consent was obtained. CMRI was used on patients to localize the affected coronary artery and predict the affected myocardial segments. Conventional coronary angiography was the gold standard tool used to confirm the diagnosis in all patients. Other inclusion criteria included sinus heart rhythm, the ability to hold one's breath for 10–20 Sec, and normal serum creatinine. Exclusion criteria included hemodynamic instability, atrial fibrillation, MRI contraindications, claustrophobia, pacemaker or metal implants, contrast material contraindications, including known allergy, and renal insufficiency (serum creatinine greater than 1.4 mg/dl).9 guidelines, our patients were examined in the supine position, head first using a respiratory sensor and ECG gating. Additionally, a sensitivity encoding (SENSE) cardiac coil was used.A Siemens Magnetom Sola 1.5 T MRI scanner with a superconducting magnet  was used. In the current study, we followed Abdelrahman et al.2, phases: 25, number of signal averages (NSA): 1, matrix: 128 × 128, bandwidth: 125 kHz, flip angle: 200, scan time: 1 Sec, slice thickness: 8 mm, slice number: 3. (iii) An additional bolus of 0.2 mmol/kg gadopentetate dimeglumine was administered immediately following the end of the rest perfusion scan. (iv) Functional cine images were obtained in short axis view using an electrocardiographic gated, breath hold balanced fast field echo (b-FFE) sequence. During repeated breath-holds, a stack of eight to eleven short-axis views were obtained, starting from the mitral valve insertion and covering the entire left ventricle with the following parameters: TR/TE: 4.4/2.5, FOV: 300 × 300 mm2, phases: 25, NSA: 1, matrix: 128 × 128, slice thickness: 8 mm, slice number: 8–11. This sequence was carried out between the previously mentioned injection of an additional bolus of contrast and the delayed gadolinium enhancement sequences. (v) Standard delayed gadolinium enhancement imaging was performed using segmental inversion recovery balanced turbo field echo (IR-b-TFE) 10–15 min after the last intravenous bolus was injected. With the following parameters, contrast-enhanced images were acquired in the short axis plane and at least one of the long axis planes: TR/TE: 3.8/1.86, FOV: 300 × 300 mm2, inversion time (TI): 260–350, NSA: 1, matrix: 128 × 128, bandwidth: 125 kHz, flip angle: 15°, scan time: 9–15 Sec, slice thickness: 8 mm, slice number: 8–1110. The mean time of the CMRI imaging examination was about 30–35 min.For the contrast agent, all patients were cannulated with a wide bore intravenous line. The patients were subjected to a standard magnetic resonance examination, which included the following procedures: (i) Scout images were collected in orthogonal orientations to aid in the planning of the final long-axis and short-axis views. (ii) Before beginning the actual index test, perform a first pass rest perfusion imaging with scan angle geometry identical to that of the short axis cine views to carefully exclude any wraparound or trigger artifacts. This included an intravenous bolus injection of 0.025 mmol/kg gadopentetate dimeglumine (Magnevist) at a rate of 5 mL/s was followed by a flush of 20 mL of saline solution at the same rate. Scanning began approximately 10 Sec after contrast injection began and lasted approximately 1 min. A hybrid gradient echo-planar imaging pulse sequence was used to perform breath-hold first-pass perfusion MRI. This pulse sequence produces three sections   Viable myocardial segment was defined as having no myocardial scarring or having ≤ 50% myocardial scarring. Subendocardial scarring was defined as 25% myocardial scarring and partial thickness scarring as 50% myocardial scarring. (ii) A nonviable myocardial segment was defined, as scarring that was > 50% of the thickness of the myocardium. On delayed-enhancement imaging, a no-reflow zone (microvascular obstruction) was visible as a dark region surrounded by hyperenhancing myocardium and/or a first pass resting perfusion defect corresponding to delayed myocardial enhancement. The results of the CMRI were compared to the results of the corresponding conventional coronary angiograms in this study.Results of CMRI in the current study were subdivided into two groups the same as in the study of Abdelrahman et al.11. CMRI sequences used in IHD patients in the current study  Consider a single-shot module or free breathing with real-time image acquisition if patient has trouble with breath holding, arrhythmia, or motion artifacts. (ii) Consider using an abdominal band to reduce artifacts in cases of difficulty due to extensive respiratory motion. (iii) In cases of difficulties due to pericardial effusion and a weak ECG signal, considered a peripheral pulse gating. (iv) If there are difficulties due to ghost artifacts caused by pleural effusion and respiratory difficulties, considered postponing the CMRI imaging until after pleural effusion drainage. These IHD patient preparation guidelines for CMRI were consistent with the Asian Society of Cardiovascular Imaging (ASCI) standardized practice protocol for cardiac magnetic resonance imaging12.CMRI was performed using the precise planes required for imaging. MRI technologists in this study were familiar with various image axes for accurate imaging interpretation, despite the fact that recent MRI units provide a support system for the CMRI plane. The imaging plane of CMRI in IHD patients used in this study was consistent with the KOSCI practical and standard CMRI protocol and guideline for CMRIE and PFRA), were calculated13. CMRI at 1.5 T necessitates protocol optimization, careful shimming, and RF pulse adjustment to avoid artifacts. Furthermore, when using Gadolinium-based MRI contrast agents, it is critical to reduce the relaxation times of nuclei within the body. These considerations and patient safety applied in this study were similar to the considerations and patient safety of CMRI in IHD patients stated in the KOSCI guideline for CMRI12.CMRI analysis was performed with a personal computer and semiautomated software . The analysis consisted of three major steps: First, in all cardiac phases, the LV endocardial and epicardial borders were delineated in all planes; second, the systolic descent and twist of the mitral valve was calculated by tracking valve motion on the long axis cines and used to correct for systolic LV volume loss due to atrioventricular ring descent; and third, blood pool thresholding was used to distinguish the papillary muscles. The LV mass was calculated using end-systolic frames. The LV volume/time curve generated from all frames of all cines was used to calculate end-systolic (ESV) and end-diastolic (EDV) volumes, and there was no requirement to choose the largest and smallest ventricular frames. The difference between EDV and ESV was used to calculate stroke volume (SV), and EF was calculated as SV/EDV. When measuring mass , papillary muscles were included, but not when measuring volume . The longitudinal atrioventricular plane descent was measured in the septum and lateral wall and expressed as a ventricular length ration. Finally, the end-diastolic and end-systolic sphericity indexes were calculated. The diastolic function was calculated from the time/volume curve's derivative and expressed as a peak filling rate (PFR). The ratio, as well as the early and active peak filling rates  mapping, and coronary angiography are among the CMRI exam modules used in this study in IHD patients. Table 12.Cine imaging, perfusion imaging, LGE imaging, flow imaging, morphological imaging, tissue characterization Tt-test (unpaired t-test) was used to compare variables. The significance of the findings was determined using the P-value. A p ≤ 0.05 value was considered significant. The binomial test was used to compare observed frequencies of symptoms and lifestyle risk factors in IHD patients to a given probability parameter . To determine the significance of the findings, the test was performed with a one-tailed alternative. A statistical diagnostic test was performed on the study samples to determine the sensitivity, specificity, accuracy, positive and negative likelihood ratio, and positive and negative predictive value of CMRI in the diagnosis of IHD. The probability that a test result will be positive when the disease is present is referred to as sensitivity (true positive rate). The probability that a test result will be negative when the disease is not present is referred to as specificity (true negative rate). The overall probability that a patient is correctly classified is referred to as accuracy. The positive likelihood ratio is the ratio of the likelihood of a positive test result given the presence of the disease to the likelihood of a positive test result given the absence of the disease. The negative likelihood ratio is the ratio of the likelihood of a negative test result in the presence of the disease to the likelihood of a negative test result in the absence of the disease. Finally, positive predictive value (PPV) is the probability that the disease exists when the test is positive, whereas negative predictive value (NPV) is the probability that the disease does not exist when the test is negative.The Statistical Package for the Social Sciences version 20 for Windows  was used to analyze the data, and the results were initially summarized in the form of comparison tables and graphs. All study variables were presented as mean ± SD because the obtained data had a symmetric normal distribution. The Student's One hundred  patients with IHD were enrolled prospectively in this study after providing written and verbal consent and receiving approval from the local ethics committee at the Radiology and Medical Imaging Department, KFMC, Riyadh, Saudi Arabia (Table p ≤ 0.05), whereas angina (chest pain), shortness of breath, sweating, weakness, dizziness, nausea, tachycardia, and palpation were significantly associated with IHD in female patients (p ≤ 0.05).The symptoms detected in IHD male and female patients include sweating 90.2%; 71.8%), weakness , angina , shortness of breath , dizziness , and nausea , respectively . In female patients, smoking, non-vegetarian diet intake, high fat intake, lack of physical activity, and obesity were significant lifestyle risk factors for IHD (p ≤ 0.05).Lifestyle risk factors of IHD patients in the current study were smoking 88.5%; 5.1%), absent physical activity , high fat intake , non-vegetarian diet intake 29.5%; 38.5%), obesity , and alcohol intake  in male and female patients, respectively 13. Gender had a significant independent influence on normalized LV volume in a multivariate analysis13. In terms of the effect of age on LV parameters, females had a significant decrease in absolute and normalized ESV with increasing age (p = 0.013)13. Normalized EDV decreased with age in both men and women (p = 0.019)13. LVEF did not change significantly with age in either men or women. Age was found to be an independent predictor of all absolute and normalized ventricular volumes in a multivariate analysis . With age, both absolute and normalized ventricular volumes decreased significantly13.These findings could be compared with our results on age-decile LV volumes and systolic function in IHD male and female patients using CMRI, which were presented in (Tables The effect of gender on LV volume reveals that males have significantly larger LV volumes (n Tables  and 7.One of the most significant strengths of this study is that it used a diagnostic test to reveal the sensitivity, specificity, and accuracy of CMRI in the diagnosis of IHD in Saudi patients, after each case had been confirmed using conventional angiography as the gold standard tool. Whereas it has been statistically proven that CMRI had a sensitivity, specificity, and accuracy in the diagnosis of IHD Table  which isIn conclusion, CMRI provides a comprehensive assessment of LV function, myocardial perfusion and viability, and as well as the coronary anatomy. One of the most significant strengths of this study is that it revealed the sensitivity, specificity, and accuracy of CMRI in the diagnosis of IHD in the patients and that was after the confirmation of the diagnosis of each case was confirmed using the conventional angiography as the gold standard tool.


Both stenosis rate and intraplaque hemorrhage (IPH) are important predictors of stroke risk. Simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) cardiovascular magnetic resonance (CMR) imaging can detect both stenosis rate and IPH. We aimed to evaluate consistency between SNAP and digital subtraction angiography (DSA) to assess symptomatic patients with stroke and explore the performance of SNAP to identify IPH and the clinical factors associated with IPH.Eighty-one symptomatic patients with stroke, admitted to Wuhan Union Hospital who underwent CMR high-resolution vessel wall imaging (HR-VWI) and SNAP, were retrospectively identified. For patients who received interventional therapy, the imaging functions of SNAP and HR-VWI were compared with DSA. The diameters of the intracranial and carotid vessels were measured, and stenotic vessels were identified. The consistency of SNAP and HR-VWI in identifying IPH was also examined, and the correlations between IPH and clinical factors were analyzed.SNAP-DSA = 0.917, ICC HR-VWI-DSA = 0.878). Regarding the diameter measurements of each intracranial and carotid vessel segment, SNAP was superior or similar to HR-VWI, and both were consistent with DSA in the measurement of major intracranial vascular segments. HR-VWI and SNAP exhibited acceptable agreement in identifying IPH . Patients who underwent interventional therapy had a higher plaque burden (P < 0.001). Patients with IPH had lower levels of high-density lipoprotein cholesterol (HDL) (P = 0.038) and higher levels of blood glucose (P = 0.007) and cystatin C (P = 0.040).SNAP was more consistent with DSA than HR-VWI in measuring vascular stenosis (intraclass correlation coefficient [ICC]CMR SNAP is consistent with DSA in measuring vessel diameters and identifying atherosclerosis stenosis in each intracranial and carotid vessel segment. SNAP is also a potential alternative to HR-VWI in identifying stenosis and IPH.The online version contains supplementary material available at 10.1186/s12968-022-00849-1. Intracranial and carotid atherosclerotic disease are the major causes of ischemic stroke worldwide, especially in Asia . The risA growing body of evidence suggests that the composition and burden of plaques are important for stroke assessment and prognosis , 15. IPHThere are few studies comparing the performance of SNAP and DSA in assessing arterial stenosis in the head and neck vessels, as well as the association between IPH and clinical factors. The present study aimed to compare the performance of SNAP with DSA in measuring luminal stenosis of the head and neck arteries. It also explored the value of SNAP in identifying IPH and the clinical factors associated with IPH to provide an effective imaging basis for improving diagnostic and therapeutic efficacy.Data from symptomatic patients with stroke, admitted to the Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology  from January 2019 to January 2020, were retrospectively analyzed  symptomatic inpatients (18 to 80 years); (2) recent stroke (within the first two weeks after admission); (3) underwent both SNAP and HR-VWI, with or without interventional therapy . Exclusion criteria were: (1) non-atherosclerotic causes of stroke, such as Moyamoya disease, vasculitis, and arterial dissection; (2) hemorrhagic stroke; (3) cerebral neoplasm; (4) cardiogenic stroke ; (5) poor-quality CMR images; (6) contraindications for gadolinium-based contrast agent administration.Clinical data were extracted from the patient’s electronic medical records, including age, sex, height, weight, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). Traditional vascular risk factors, including hypertension, smoking, alcohol, diabetes, hyperlipidemia, and levels of total protein, serum amyloid A (SAA), total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides were also obtained. All biochemical markers mentioned in our study were measured using routine biochemical tests within two weeks of admission.Patients underwent vessel wall imaging on a 3 T CMR system  with a combination of a 32-channel head coil  and an 8-channel neck coil . The imaging protocols are summarized as follows: 3-dimensional (3D) time-of-flight (3D-TOF), 3D SNAP in both transverse and coronal orientations, multi-sequence HR-VWI  VISTA), T1-weighted inversion recovery (T1w-IR), T2-FLAIR-weighted (T2w-FLAIR), and diffusion-weighted-imaging (DWI). 3D-TOF, T1w, T2w-FLAIR, and DWI were used to identify symptomatic patients with stroke. 3D-TOF imaging was used to detect arterial stenosis. Moreover, the T1w imaging, T2w-FLAIR, and DWI were used to find infarcted intracranial lesions. We also used 3D SNAP, 3D T1-VISTA, and 3D T2-VISTA to assess both intracranial and extracranial arterial stenosis and plaque. The T1/T2-VISTA sequences were used to identify the atherosclerotic plaques and their compositions, and the contrast-enhanced T1-VISTA imaging to further determined the nature of the plaque and to measure the degree of stenosis.2; slices = 150; slice thickness = 0.55 mm; acquisition matrix size = 500 × 332; reconstruction voxel size = 0.4 × 0.4 × 0.55 mm3; parallel acquisition factor = 3; and scan time = 4 min and 15 s. For T1w imaging: turbo spin echo (TSE) sequence, TR/TE = 2000/16 ms; acquisition matrix size = 288 × 204; slice thickness = 5 mm. For T2w-FLAIR: TSE sequence, TR/TE = 9000/125 ms, acquisition matrix size = 384 × 192; slice thickness = 5 mm. For DWI: spin echo (SE) sequence, TR/TE = 2732/77 ms; acquisition matrix size = 152 × 106; FA = 90°; slices = 23; slice thickness = 5 mm. DWI was obtained with b values of 0 and 1000 s/mm2.The main imaging parameters were as follows: For 3D TOF CMR angiogram (CMRA): fast field echo (FFE) sequence, repetition time (TR)/echo time (TE) = 23/3.5 ms; flip angle (FA) = 18°; field of view (FOV) = 160 × 160 mm3; compressed sensing factor = 3; scan time = 4 min and 52 s. For T2wVISTA: TSE sequence, TR/TE = 1800/214 ms; FA = 90°; acquisition matrix = 416 × 270; slice thickness = 0.6 mm; reconstruction voxel size = 0.6 × 0.6 × 0.6 mm3; compressed sensing factor = 3; and with SPAIR fat suppression, scan time = 4 min and 26 s. For SNAP: FFE sequence, TR/TE = 11/5.9 ms; FA = 11°; inversion time = 500 ms; FOV = 160 × 160 mm2; slices = 150, slice thickness = 0.8 mm; acquisition matrix size = 200 × 200; reconstruction voxel size = 0.4 × 0.4 × 0.4 mm3; parallel acquisition factor = 2; scan time = 3 min and 2 s.For T1w VISTA: TSE sequence, TR/TE = 600/26 ms; FA = 90°; acquisition matrix = 416 × 270; slice thickness = 0.6 mm; reconstruction voxel size = 0.6 × 0.6 × 0.6 mmTwo radiologists  analyzed the imaging examinations results independently using Vessel Explorer 2.0 software . Both were blinded to patients' clinical characteristics. HR-VWI and SNAP assessments were performed independently, and the interval between the two radiologists’ assessments was about one month. The results of HR-VWI/SNAP were also evaluated independently against the DSA results, and the evaluation interval between the HR-VWI/SNAP and DSA was also about one month. In addition, both radiologists also investigated the location and number of IPH on the SNAP images. The lumen, wall, and IPH components of SNAP and HR-VWI were manually delineated , 19.Disagreements were resolved by discussion between the two radiologists. If an agreement could not be reached, a senior radiologist (J.W. with 12 years of neuro-radiology experience) would repeat the measurements and come to a consensus.Multi-contrast vessel wall imaging of arteries of the head and neck arteries  was reconstructed using the software to measure luminal stenosis via the North American Symptomatic Carotid Endarterectomy Trial (NASCET) algorithm or the Warfarin-Aspirin Symptomatic Intracranial Disease Study (WASID) algorithm , 21. TheSPSS  was used for statistical analyses. Continuous variables are presented as the mean ± standard deviation (SD), and categorical variables are presented as the frequency and percentage. For clinical factor analyses, an unequal number of patients with or without IPH was matched according to the age distribution and sex ratio of the two groups. The Chi-square and McNemar’s tests were used to assess associations between the presence of IPH and vascular risk factors. Nonparametric test was used to investigate the relationship between the presence of IPH and clinical data when the data were abnormally distributed. The intraclass correlation coefficient (ICC) and Bland–Altman plot with 95% confidence intervals (CIs) were calculated to evaluate intraclass and intergroup reproducibility in diagnosing the degrees of stenosis. The Kappa value was used to evaluate the consistency between SNAP and HR-VWI in identifying IPH. Statistical significance was set at P < 0.05.Eighty-one symptomatic patients with stroke were identified Table  54.6 ± . PatientThe location and number of IPH were counted in patients with IPH Table . A totalintraclass = 0.960) and between the two readers (ICCinterclass = 0.889) were satisfactory  and HR-VWI (ICCHR-VWI-DSA = 0.878) both showed good agreement with DSA the measurement of luminal stenosis  imaging in identifying intraplaque hemorrhage (IPH) at different sites of intracranial and carotid arteries. Fig. S1 The agreement between simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) and high-resolution vessel wall imaging (HR-VWI) with digital subtraction angiography (DSA) in measuring the diameter of different intracranial and carotid arterial segments.


Objective: Immune checkpoint inhibitors (ICIs) are effective anti-cancer drugs that can improve survival in cancer patients, but their use may be associated with adverse cardiovascular side effects. Therefore, there is a clinical unmet need to identify non-invasive biomarker to detect subclinical cardiac toxicity after ICI treatment. The aim of this study is to examine the plasma levels of biomarkers in cancer survivors who were treated with ICIs.Patients and Methods: In a cohort of 19 cancer patients, biomarkers were evaluated at baseline, 1 month, 3 and 6 months after ICI administration. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included cardiac troponin I (cTnI), high-sensitivity C-reactive protein (Hs-CRP), N-terminal pro–B-type natriuretic peptide (NT-pro BNP), CK (creatine kinase), CK-MB (creatine kinase-MB), Pentraxin-related protein 3 (PTX3), growth differentiation factor 15 (GDF-15), heart type-fatty acid binding protein (H-FABP) and galectin 3 .Results: H-FABP, but not other biomarkers, were increased at 3 months, which persisted at 6 months . Left ventricular ejection fraction  was not significantly reduced at this time point.Conclusions: H-FABP, but not other biomarkers, were increased in patients who were treated using ICIs. H-FABP might be a more sensitive biomarker to detect ICI-related subclinical myocardial damage than traditional cardiac biomarkers. Utilizing the immune system to recognize and target malignant cells has been a strategy used in oncology for many years . In the 2); thyroid disease; acute infectious diseases; mental illness; life expectancy is less than 6 months.The study protocol was approved by the institutional review boards of the participating institutions. The study is registered with the Chinese Clinical Trial Registry (registration number: ChiCTR18000162216). All participants provided informed consent. A total of 19 consecutive patients who never used the ICIs and hospitalized in the Oncology Department of Tianjin Medical University Second Hospital from June 2018 to June 2019 were enrolled to the study. Eligible patients were 18–85 years of age, diagnosed with cancer and planned for adjuvant therapy with ICIs. Patients with one of the following conditions were excluded: intolerance to ICIs treatment; severe left main coronary artery disease confirmed by angiography; presence of grade III or IV heart failure; acute myocardial infarction (acute or recovery period); hepatic insufficiency (AST/ALT >80U/L); severe renal insufficiency (eGER ≤ 30 m/min/1.73 mAt baseline (before immune-therapy) and 1month, 3 months, 6 months after ICIs administration, demographics and clinical history were recorded. Transthoracic echocardiograms were obtained at each visit, and blood samples were obtained immediately before cancer therapy infusion at 1, 3, 6-month intervals.A transthoracic echocardiographic examination was performed in all patients using the Vivid-7 system equipped with a 2.4 MHz transducer . Left ventricular end systolic diameter (LVEDS), left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were obtained using Simpson’s method of discs in the apical 4- and 2-chamber views as recommended by the American Society of Echocardiography. All tracings were made by a single observer and the data measurement is done by two ultrasound doctors at a centralized reading center who was blinded to all other clinical or biomarker data.At the time of the echocardiography, venous blood samples were drawn from all participants and collected in standard tubes for plasma with EDTA. Place the collected blood samples properly, it is strictly forbidden to freeze whole blood to avoid hemolysis. After the blood culture sampling is completed, it should be sent to the biological laboratory for verification by a dedicated person immediately, generally not more than 2 h hemolysis specimens centrifuged at 3,000 rpm for 15 min, plasma was removed, allocated, and frozen at −80°C until assay. Measurement of cTnI, NT-proBNP, CK, CK-MB, Hs-CRP were performed on the clinical Laboratory System. Serum levels of GDF-15, Gal-3, PTX3 and H-FABP were assayed using commercially available ELISA kit . All measurements were performed on previously unthawed samples. Concentrations of unknown samples are determined using a standard curve that was constructed by plotting absorbance values against concentrations of the standards.p value of <0.05 was regarded as statistically significant. All tests were two tailed and analyses were performed using SPSS 22.0 Statistical Package Program .Each biomarker was evaluated at baseline, 1 month, 3 and 6 months. The normality of the distribution of each continuous variable was tested by the Kolmogorov–Smirnov test. Continuous variables were reported as means ± SD or median (interquartile range) as appropriate. Statistical analysis was performed using the ANOVA test for continuous variables. A N = 19) who using ICIs was 48.2 ± 11.6 years with 42.1% being male. Prior to ICIs administration, only one patient had previous myocardial infarction and coronary stenting, but the left ventricular ejection fraction (LVEF) was >50% in all those with a baseline measurement.The baseline characteristics of the study cohort are shown in The most common indications for ICIs were Renal cell carcinoma, lung cancer and female reproductive system tumor. Of the monotherapy at the time of presentation, anti-PD1 was the most frequent (63.1%) in cases. For better therapeutic effect and clinical prognosis, single ICI therapy administrated with radiation or other chemotherapy is presented in Cardiac function and biomarkers at 1, 3, 6 months after ICI therapy compared to baseline.p = 0.608), LVEDD (p = 0.105) or LVEDS (p = 0.178) 6 months after ICI therapy. , whereas GDF-15 was significantly lower only at 6 months (p = 0.017). Gal-3 was not significantly altered whilst PTX3 was significantly reduced at 1 month , D-dimer (p = 0.219), CK (p = 0.059) and CK-MB (p = 0.92) were observed at 1 month, 3 and 6 months  are relatively small cytoplasmic proteins that are abundant in tissues with active fatty acid metabolism, including the heart and the skeletal muscles. In fact, heart-type FABP (H-FABP) is particularly important for cardiomyocyte energy homoeostasis, since 50–80% of the heart’s energy is provided by the oxidation of fatty acids and H-FABP ensures intracellular transport of insoluble fatty acids. Following myocardial cell damage, H-FABP diffuse much more rapidly than troponins secretion into the interstitial space and appears in the circulation as early as 90 min after the onset of symptoms. Recently, H-FABP has become a newer perspective marker for the early detection of myocardial ischemia and necrosis, evaluated in the diagnostics and risk stratification of acute coronary syndromes . ExperimGal-3 is a 26-kDa protein that is expressed by macrophages, plays a prominent role in tumor growth, metastasis, angiogenesis, and immune evasion and is believed to be a mediator of profibrotic pathways, stimulating cardiac fibroblasts to proliferate and deposit collagen. Gal-3 concentrations are elevated in patients with acute HF and are predictive of an increased risk of adverse outcomes . On the PTX3 is a member of the pentraxin family, the prototype of the pentraxin family is C reactive protein (CRP), a widely used clinical biomarker in human pathologies with an inflammatory or infectious origin . NowadayThere are several limitations of this study. Firstly, a relatively small number of patients was enrolled. Further studies in a larger number of patients will be needed to define the potential role of new circulating biomarkers in the assessment of ICIs-induced subclinical myocardial injury. Secondly, follow-up was relative short at 6 months. Thirdly, myocarditis is more prevalent in patients with combined use of CTLA-4 and PD-1/PD-L1, but CTLA-4 has not yet been marketed in the Mainland and was therefore not included in this study. Lastly, the application of imaging such as cardiac magnetic resonance imaging (CMR) or speckle-tracking echocardiography would be able to quantify the degree and location of cardiac dysfunction more precisely. had been resonated, the accuracy of the diagnosis could be improved. For example, speckle tracking imaging is recommended by ESC for detecting subclinical cardiac damage. It can be used in combination with measurements of H-FABP levels for further patient monitoring and risk stratification.H-FABP, but not other biomarkers, were increased in patients underwent ICIs therapy. H-FABP might be a more sensitive biomarker to detect ICI-related subclinical myocardial damage than traditional cardiac biomarkers.


Decreasing signal intensity of the spleen assessed by T2* MRI is a frequent finding in patients with beta-thalassemia due to iron deposition within the reticuloendothelial cells in this organ. This parameter can also be applied to determine the candidates for blood cell transfusion. However, the association between splenic siderosis and iron overload in other vital organs such as heart and liver remains unclear. The present study aimed to assess the correlation between iron deposition in splenic, hepatic and myocardial tissues by T2* relaxometry technique.This cross-sectional study included 39 consecutive patients with a definitive diagnosis of beta-thalassemia major who underwent spleen, liver and heart MRI examinations for iron deposition and cardiac function.ROC curve analysis, the splenic T2* could significantly, but moderately predict moderate to severe from mild liver iron excess (AUC=0.667).No significant correlation was found between the heart and splenic T2* relaxation time . We revealed a strong correlation between the splenic T2* relaxation time and hepatic calculated T2*s . The liver T2* values can be predicted from the splenic T2*s by a new linear equation. According to the Our study demonstrated a significant linear correlation between the splenic and hepatic T2* relaxation time, probably indicative of the same iron deposition mechanism, and made us available to write a linear model that would predict the deposited iron density in the spleen with the use of the magnetic resonance T2* values. In beta-thalassemia patients, varying mechanisms, transfusion and non-transfusion-dependent, are responsible for iron loading. This phenomenon can be first developed by increasing iron absorption from the intestine signalled by ineffective erythropoiesis that might be secondary to transfusion . SuppresMore than all, heart and liver are significantly affected by iron overloading. The occurrence of cardiac iron overloading commonly leads to cardiac siderosis, a severe source of cardiac arrhythmia, heart failure, and even death, especially in patients with transfusion-dependent thalassemia . In thisMore interestingly, in non-transfusion-dependent thalassemia, the liver is involved rather than the myocardium leading to liver fibrosis and chronic, increase the risk for viral hepatitis cirrhosis and even hepatic failure .Along with clinical evaluation, some recent imaging techniques such as magnetic resonance imaging using R2 or T2* techniques have been introduced as a good alternative for invasive management via biopsy for the assessment of iron overload . Although histological assessment has been known as a highly sensitive and specific for assessing iron overload in vital organs, the diagnostic performance of R2 or T2* MRI in this goal has received strong attention . MRI is As a new suggestion, because the spleen and lymph nodes are reticuloendothelial cells-rich organs, the effect of these organs via iron overload is also expected ; howeverStudy Population: This cross-sectional study included 39 consecutive patients with a definitive diagnosis of beta-thalassemia major who underwent spleen, liver, and heart MRI examinations for iron deposition and cardiac function. All national and international ethical research rules were supervised by the institution's ethics research committee, and the researchers followed the rules completely. MRI Examination: All the MRI examinations were performed using a 1.5 Tesla MR system . The protocol was identical for all patients. A 16-channel phased-array body Radiofrequency (RF) coil was employed for the signal reception. All the sequences were ECG-gated either retrospectively or prospectively. For cine imaging, several 2D, Breath-held, True-Fast Imaging with Steady State Precession MRI (True-FISP) were performed retrospectively in the 2-chamber, 4-chamber, and a whole-heart coverage short-axis views in all the patients assess- ing the left ventricular function qualitatively and quantitatively tFor T2* mapping, the cardiac T2* relaxometry data were acquired by a breath-held, Bright-Blood, Gradient-Recalled-Echo pulse sequence which could obtain 8 signals with different echo-times (TE) in each repetition-time (TR). The patients' hearts were imaged in the three cardiac basal, mid-ventricular, and apical short-axis, and three spleen and hepatic transverse planes by the given parameters  for quantitative variables and were summarized by absolute frequencies and percentages for categorical variables. Normality of data was analyzed using the Kolmogorov-Smirnoff test. The association between the quantitative variables was examined by the Pearson’s correlation test or Spearman’s non-parametric correlation test. The receiver operating characteristic (ROC) curve analysis was employed to assess the value of splenic T2* in predicting the severity of iron excess in the heart and liver. The Statistical Package for the Social Sciences (SPSS),  was used for analysis. P-values of 0.05 or less were considered statistically significant. All the data used in the analysis were labeled, hence the statisticians were blind to the groups.Overall, 98 region of interests (ROIs) were drawn for all patients who participated in our study. 37 ROIs were drawn in liver (mean: 4.1868±5.1317 ms), out of which 23 ROIs were classified as the severe iron overload, 10 ROIs with moderate iron overload, and 4 with mild iron status. Also, 38 ROIs were drawn in the myocardial inter-ventricular septum (mean: 23.3776±11.3660 ms), out of which, 7 ROIs were diagnosed with severe iron deposition and 31 with mild status. No moderate myocardial iron deposition was noticed among the patients. From the total 98 regions of interest, 21 ROIs were drawn in the middle of the splenic tissue (mean: 16.0136±17.0022 ms). Due to the non-parametric nature of all quantitative parameters assessed, the bivariate two-tailed Spearman’s correlation test was performed between the splenic and myocardial iron deposition statuses  and indiAccording to the ROC curve analysis , the splDecreasing signal intensity of the spleen assessed by T2* MRI is a common finding in patients with beta-thalassemia frequently due to iron deposition within the reticuloendothelial cells in this organ , 18. ThiMRI plays a pivotal role in planning the beta-thalassemia major treatment strategy. The hepatic biopsy is the gold standard method to measure the iron deposition density; however, as an invasive method, it has limitations for repeated assessment. Hence, MR relaxometry could be a suitable tool for patients' annual assessment. There were numerous studies evaluating the role of MRI and its accuracy in in-vivo iron measurements by the use of T1, T2, and T2* relaxometry methods. By recent investigations, it has been proven that the T2* relaxation time was the most robust phenomenon by the iron deposition density. In the recent years, many studies have been done on the hepatic and myocardial iron deposition density and kinetics by the use of T2* relaxometry, but few were done on spleen and the endocrine system. In this study, we assessed the linear/curvilinear relationship between the splenic and hepatic/myocardial T2* relaxation times, to find the similarities of iron deposition mechanisms and acquire a robust relationship between the splenic iron content and its quantitative T2* values based on the previous studies. Our study demonstrated a significant linear correlation between the splenic and hepatic T2* relaxation times, probably indicative of the same iron deposition mechanism, and made us available to write a linear model that would predict the deposited iron density in spleen by the use of the magnetic resonance T2* values.Ethical considerations: The protocol of the study was approved by the Ehics Committee of Iran University of Medical Sciences with the number of IR.IUMS.REC.1396.9211282015. Design and objectives of the study were explained to the parents and written informed consent was obtained from those who were willing to participate in the study and they were ensured that their information will be kept confidential and analyzed anonymously. All the ethical considerations of Helsinki declaration were met throughout the study.


Congenital complete heart block is defined as a complete atrioventricular block occurring prenatally, at birth, or within the first month of life. Congenital complete heart block has a high mortality rate, and in infants with normal heart morphology, it is often associated with maternal connective tissue disease. In these latter cases, neonatal congenital complete heart block is usually irreversible. We present a rare case of a female neonate who had bradycardia noted at a gestational age of 37 weeks. Her mother had no autoimmune disease history. She had no structural heart disease, and the serology surveys for autoantibodies including SSA/Ro and SSB/La were all negative. Without intervention or medication, her congenital complete heart block completely recovered to a normal sinus rhythm within 5 days. The cause of the transient congenital complete heart block was unknown in this case. Congenital heart block is defined as an atrioventricular block occurring prenatally, at birth, or within the first month of life, and it has a high mortality rate . A congeA female neonate was born to a 29-year-old gravida 3 para 2 abortus 1 mother at the gestational age of 37 weeks with unremarkable prenatal laboratory results and an unremarkable second trimester anatomic ultrasound. She had no past history of autoimmune disease, and no medication was used during pregnancy. The fetal heartbeat (FHB) decreased to less than 60 bpm during a routine prenatal examination, and the infant was delivered via an emergency Cesarean section on the same day.The baby cried well soon after birth, and the Apgar score was 8 at both 1 and 5 min after birth. The amniotic fluid was clear without meconium staining. The birth body weight was 2615 g, which was appropriate for the gestational age. She was admitted to the neonatal intensive care unit. On admission, bradycardia (heart rate: 70 bpm) was noted but the pulse was strong and no hypotension was detected (blood pressure: 70/29 mmHg). The peripheral saturation was 100% in room air. The electrocardiogram (ECG) showed a complete atrioventricular (AV) block with an atrial rate of 158 bpm and a ventricular rate of 75 bpm . EchocarThe patient was hemodynamically stable under continuous ECG monitoring in the neonatal intensive care unit. The heart rate was between 63 and 93 beats per minute without any signs of hypoperfusion. She received neither respiratory support nor inotropic agents, and there was no metabolic acidosis. A temporary pacemaker implantation, although initially planned, was eventually not performed because of the constant good clinical condition, sufficient perfusion, and acceptable heart rate. Repeated 12-lead ECG follow-up at 3 days of age indicated a change to a Mobitz type I second degree AV block with an atrial rate of 144 bpm and a ventricular rate of 60–90 bpm . To diffComplete congenital heart block increases the risk of morbidity and mortality in utero and in the first few months of life 15–30%) ,8. Compl5–30% ,8.In SSA/Ro- or SSB/La-positive mothers, the risk of developing complete congenital heart block lies at about 1–2%. The mother may have symptoms of systemic lupus erythematosus or Sjögren’s syndrome or may be asymptomatic . It is uReports of a spontaneous recovery from idiopathic complete congenital heart block are scarce. Four fetal cases of a transient heart block at 18 to 35 gestational weeks were reported in 2005. The heart blocks were diagnosed by fetal ultrasonography and were spontaneously resolved in 4 weeks. None of these mothers or infants had connective tissue disease, and the SSA/Ro and SSB/La antibodies were both negative. Maturation of the balance between the parasympathetic and the sympathetic nervous systems or myocardial ischemia might be the cause, but the cause of the transient fetal heart blocks was still unknown in this report . The parIn this case report, the infant had a complete congenital heart block in the third trimester and spontaneously reverted back to a normal sinus rhythm 5 days after birth. Although the serology surveys for autoantibodies were negative, undetected transplacental maternal autoantibodies or unreported events might have been possible causes of the transient complete congenital heart block. The presented case demonstrates that spontaneous recovery of complete congenital heart block is possible in infants without detectable autoantibodies.