The tissue contrasts generated from conventional MRI and synthetic MRF also showed agreement in bone, muscle, and uterus for both T1-weighted and T2-weighted images. This study highlights the strengths of MRF in providing simultaneous T1 and T2 mapping. MRF offers distinct tissue contrast and has the potential for accurate diagnosis of female pelvic diseases, including tumors, fibroids, endometriosis, and pelvic inflammatory disease. Additionally, MRF shows promise in monitoring disease progression or treatment response. Overall, the study demonstrates the potential of MRF in the field of female pelvic organ imaging and suggests that it could be a valuable addition to the clinical practice of pelvic MRI exams. Further research is needed to establish the clinical utility of MRF and to develop standardized protocols for its implementation in clinical practice.The aim of this study was to explore the potential of magnetic resonance fingerprinting (MRF), an emerging quantitative MRI technique, in measuring relaxation values of female pelvic tissues compared to the conventional magnetic resonance image compilation (MAGiC) sequence. The study included 32 female patients who underwent routine pelvic MRI exams using anterior and posterior array coils on a 3T clinical scanner. Our findings demonstrated significant correlations between MRF and MAGiC measured T1 and T2 values ( Medical imaging plays a crucial role in precision medicine by providing quantifiable features . MagnetiMagnetic Resonance Image Compilation (MAGiC), on the other hand, is a technique that allows for the acquisition of multiple images contrasts in a single MRI scan by acquiring several images with varying contrast weightings, including T1-weighted, T2-weighted, and proton density-weighted images. This approach is primarily used in neuroimaging  but has The objective of this prospective study was to examine the relaxation values of the female pelvis using MRF and compare the obtained quantitative T1 and T2 values with those obtained from the MAGiC sequence.We prospectively enrolled 49 female patients between May 2020 and August 2021 who were scheduled for routine pelvic MRI exams. Informed consent was obtained from all study subjects, and the study was approved by the Chang Gung Institutional Review Board (IRB 201702080A0C601). The inclusion criteria were females aged over 20 years who were either in pre-operative or post-operative status for gynecological disease. The exclusion criteria included patients without available MRF or available MAGiC and suboptimal MR image quality. The study flow diagram is shown in A 3T clinical scanner  with anterior and posterior array coils was used to perform all MRI acquisitions. A 2D fast-spin-echo multi-saturation-delay multi-echo is employed for MAGiC acquisition. MRF was acquired using Steady-state free precession (SSFP), and the acquisition trajectories utilized under-sampled golden-angle spiral interleaves with sampling bandwidth = ±250 kHz, TE = 2.2 ms, NEX = 1, and 979 frames. The variable repetition time and scan flip angle list were adapted from Jiang et al. . A slice2. Contrast-enhanced T1WI was acquired after intravenous injection of 0.1 mmol/kg body weight of contrast medium  followed by a 20-mL saline flush, at about 120–180 s equilibrial phases. The T1WI was acquired with a TR of 567 ms, a TE of 10 ms, a flip angle of 150°, 2 signal averages, a matrix of 256 × 320, and a FOV of 20 cm. The scan was performed during normal respiration and minimal breathing, and no premedication was administered.Conventional MRI was also performed in the same study session. In brief, T1-weighted and T2-weighted turbo spin-echo sequences were applied with specific parameters: for T1, a repetition time (TR) of 626 ms and an echo time (TE) of 11 ms, with 2 signal averages and a matrix of 256 × 320, and a field of view (FOV) of 20 cm; for T2, a TR of 5630 ms and a TE of 87 ms, with 3 signal averages and a matrix of 256 × 320, and a FOV of 20 cm. Diffusion-weighted imaging (DWI) was carried out using a single-shot echo-planar technique with fat suppression, with a TR of 3300 ms and a TE of 79 ms, 4 signal averages, a matrix of 128 × 128, and a FOV of 20 cm, in 5-mm trans-axial plane. The diffusion-weighted gradients were applied orthogonally in slice-selective, phase encoding, and read-out directions. Apparent diffusion coefficient (ADC) maps were generated from isotropic diffusion-weighted images with b values of 0 and 1000 s/mmwww.itksnap.org, assessed on 2 February 2022) [Quantitative MAGiC T1 and T2 maps were generated from the MAGiC raw image dataset using SyMRI 8 software . MRF T1 and T2 maps were obtained by pattern matching of the T1 and T2 simulation dictionary with reconstructed time frames of the acquired data. The MRF dictionary was computed for T1 and T2 using the extended phase graphs formalism  and inclry 2022) .In this study, different types of tissues were selected for a qualitative comparison between MRF and T1WI and T2WI. The categories of tissues included bone, muscle, fat, uterus, vessel, and urine. To compare the signal intensity characteristics of these tissues, the signal intensity of all tissues on T1WI and T2WI was defined in comparison to the fatty bone marrow in the pubic symphysis, which was considered as a reference . The sigFor quantitative analysis, we calculated the Pearson correlation coefficient (r) to assess the correlation between T1 and T2 values obtained using MAGiC and MRF . We alsop-value of less than 0.05 was considered statistically significant.For qualitative agreement analysis, we evaluated the agreement of tissue contrast between MRF and conventional T1WI and T2WI using weighted κ statistics. The statistics were used to classify the level of agreement between the two methods as poor agreement (0.00 < κ < 0.040), fair to the good agreement (0.40 ≤ κ ≤ 0.75), or excellent agreement (κ > 0.75) . A correThe flow diagram in p < 0.0001) for T1 and r = 0.68 (p < 0.0001) for T2. After excluding the rectus abdominis and bladder wall tissues, a more positive correlation between MRF-derived T1 (r = 0.86) or T2 (r = 0.86) values with MAGiC-derived values was observed. These findings suggest that MRF and MAGiC are effective methods for measuring T1 and T2 values in various tissues, with strong correlations observed in most cases.The study observed significant correlations between the MRF and MAGiC measured T1 and T2 values for various tissues, including the ilium, femoral head, gluteus, obturator, iliopsoas, erector spinae, uterus, cervix, and cutaneous fat. These correlations were considered statistically significant, implying that there is a strong relationship between the MRF and MAGiC-measured T1 and T2 values for these tissues. p < 0.001). This finding suggests that radiotherapy may have an impact on the T1 values of bone tissue. The study also found similar results for the T1 values of the ilium and femoral head tissue in patients with and without radiotherapy. Interestingly, there was a significantly lower T1 value in patients who had undergone radiotherapy compared to those who had not for both ilium (p < 0.001) and femoral head (p = 0.034) tissues.The study conducted a comparison of T1 and T2 values of bone tissue between patients who had undergone radiotherapy and those who had not. We further compared the tissue contrasts generated from conventional MRI and synthetic MRF. The results showed that there were some agreements in the tissue contrasts for bone, muscle, and uterus in both T1-weighted and T2-weighted images. The tissue contrasts were visually better in the synthetic T2-weighted imaging than in the original T1 or T2 maps of MAGiC and MRF. This suggests that the synthetic MRF technique may provide more accurate and reliable tissue contrasts for detailed pelvic structures, including ilium, femoral head, gluteus, rectus abdominis, obturator, iliopsoas, erector spinae, uterus, cervix, bladder wall, cutaneous fat, for both MAGiC and MRF. The study also found that blood vessels showed overall high signal intensity in MRF-synthetic T2-weighted imaging, even in small vessels, such as superficial epigastric vessels. However, the agreements of T1 signal intensity were poor for fat and vessel, and the agreements of T2 signal intensity were fair to good for fat and poor for the vessel.In comparison with the pubic symphysis, the signal intensity of fatty bone marrow showed T1-iso/hypo-intensity and T2-iso/hypo-intensity in both conventional MRI and MRF-synthetic weighted imaging. Similar signal intensity patterns were also noted when observing muscle and uterus. T1-hypointensity and T2-hyperintensity of urine were also noted. Excellent agreement between conventional MRI and tissue contrast generated from MRF was observed in bone, muscle, uterus, and urine for both T1W and T2W. The agreements of T1 signal intensity were poor for fat (κ = 0.152) and vessel; the agreements of T2 signal intensity were fair to good for fat (κ = 0.600) and poor for the vessel. Overall, the study demonstrated that the synthetic MRF technique might provide better tissue contrasts for detailed pelvic structures and that there were some agreements between conventional MRI and tissue contrast generated from MRF for bone, muscle, uterus, and urine. These findings may have important clinical implications, as accurate tissue contrasts are crucial for diagnosis and treatment planning in various pelvic pathologies.In the present study, we have demonstrated the effectiveness of MRF in simultaneously quantifying and visualizing tissue contrast on both T1-weighted and T2-weighted images in the female pelvis. This approach addresses the need for efficient T1 and T2 mapping in clinical applications, such as ovarian tumor characterization  and placMRF and MAGiC are two different techniques used in medical imaging. MRF generates quantitative maps of tissue properties, while MAGiC acquires multiple images contrasts in a single scan. Our study found that there is a significant correlation between the T1 and T2 values generated by MRF and MAGiC in the pelvic tissue, in line with previous studies that showed good correlation in tissues of the abdomen, such as the liver and spleen . HoweverMAGiC has a longer scan time compared to MRF, which can result in more artifacts from breathing motion, particularly in the pelvic organs of females. Additionally, MRF has demonstrated insensitivity to motion as the dictionary-matching process can reject such artifacts when a voxel is static for enough frames. Furthermore, MRF allows for the assessment of qualitative and quantitative data in a single sequence without misregistration. Our study validated MRF data using MAGiC and found significant correlations between T1 and T2 values generated from both techniques, especially for tissues other than the bladder and rectus abdominis. Drawing the thin bladder wall and rectus abdominis, along with partial volume effects at the border, may account for the error and difficulty in these areas. The application of MRF for imaging quantification of female pelvic structures shows promising potential, and diffusion imaging can also be obtained with MRF . AdditioThe study demonstrated the effectiveness of MRF in simultaneously quantifying and visualizing tissue contrast on both T1-weighted and T2-weighted images in the female pelvis, addressing the need for efficient T1 and T2 mapping in clinical applications. MRF has shown promise in examining pelvic organs, such as the uterine cervix, uterine body, rectum, urinary bladder, and even the femoral head. Additionally, MRF allows for the assessment of qualitative and quantitative data in a single sequence without misregistration and insensitivity to motion artifacts. The study validated MRF data using MAGiC and found significant correlations between T1 and T2 values generated from both techniques, especially for tissues other than the bladder and rectus abdominis. The application of MRF for imaging quantification of female pelvic structures shows promising potential, and diffusion imaging can also be obtained with MRF.Despite the promising potential of MRF in imaging quantification of female pelvic structures, there were several limitations in this study that should be acknowledged. Firstly, the sample size was small and heterogeneous, and no specific diseases were examined. This limitation may affect the generalizability of the study results to different patient populations with specific pelvic diseases. Larger sample sizes and studies focusing on specific diseases may be needed to further validate the findings of this study. Secondly, a phantom study was not conducted in this study, and references were used from external publications that also used MRF acquisition. Although external references were used to validate the MRF technique, it would have been more appropriate to have a phantom study to ensure the accuracy and consistency of the MRF technique ,21. ThirIn conclusion, the use of MRF allowed for the generation of T1 and T2 maps simultaneously, resulting in clear tissue contrast on both T1-weighted and T2-weighted images. The simultaneous generation of these maps using MRF provides a more precise diagnosis of diseases in the female pelvis. Furthermore, the potential of MRF in the field of female pelvis organ imaging is significant. The quantitative value and bone mineral density or muscle biological factors can be evaluated using MRF, which may aid in the detection of various conditions, such as tumors, fibroids, endometriosis, and pelvic inflammatory disease. MRF could be used as an opportunistic MRI in both patients with and without radiotherapy to evaluate the changes in the quantitative values and biological factors of pelvic organs. Overall, the findings of this study suggest that MRF is a promising imaging modality for the diagnosis of diseases in the female pelvis. Further research is needed to determine the full potential of MRF in this area and to develop standardized protocols for its clinical use.


DMD gene encoding dystrophin. Left ventricular noncompaction (LVNC) is a rare cardiomyopathy morphologically characterized by abnormal myocardial trabeculae and deep recesses in the left ventricle. LVNC in BMD patients has only rarely been reported.Becker muscular dystrophy (BMD) is an inherited X-linked recessive condition resulting from mutations of the DMD gene (reference sequence NM_004006.2) in two Chinese siblings with BMD and LVNC by high throughput targeted next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR). The proband was a 22-year-old man admitted with dyspnea, abdominal distention, and polyserositis. It is noteworthy that both the proband and his younger brother manifested progressive muscular atrophy and creatine kinase (CK) elevation. Light and electron microscopy examination of muscle biopsies showed the typical features of dystrophinopathies. Cardiac magnetic resonance imaging and echocardiography demonstrated that both brothers had an enlarged left ventricle, LVNC, and reduced left ventricular ejection fraction. Finally, the proband underwent heart transplantation at age 26 with an event-free follow-up over 4 years post-transplantation.In the present study, we identified a deletion mutation in exons 10 to 12 (EX10_12 del) of the This case further enriches our knowledge of the symptoms, genotype, cardiac performance, management, and prognosis of BMD patients complicated by LVNC. It is recommended that early comprehensive cardiac evaluation should be considered for patients with BMD to exclude LVNC, as this may have a significant impact on their prognosis. DMD affects about one in 3,500–5,000 newborn males with principal features of slowly progressive muscle weakness in the first few years, loss of ambulation in the second decade, and death from cardiomyopathy or respiratory failure early in the third decade of life 0200 and , 5, left2.In the studied family, the proband, a 22-year-old man, and his 20-year-old brother were born of non-consanguineous parents. Both patients exhibit normal intelligence, devoid of any other neurological symptoms, and no sign of further deterioration to date.The proband was admitted to Wuhan Union Hospital because of dyspnea, abdominal distention, and polyserositis, with progressive muscle weakness since the age of 13 years. Biochemical examination showed elevated CK at 11,933 U/L, aspartate transaminase (AST) of 164 U/L, alanine aminotransferase (ALT) of 202 U/L, and N-Terminal Pro-Brain Natriuretic Peptide (NT-pro BNP) of 9,835 pg/ml. Admission electrocardiography (ECG) showed sinus rhythm with a heart rate of 95 beats/min, deep and narrow Q waves in leads I, aVL, and V5 to V6 ,B. The tSignificantly, the proband showed typical clinical features with progressive proximal limb muscle atrophy and calf muscles pseudohypertrophy ,B. The eUnexpectedly, as the primary caregiver during hospitalization, his younger brother showed proximal limb muscle atrophy and calf muscles pseudohypertrophy similar to the proband . Based oDMD gene (reference sequence NM_004006.2) , followed by target enrichment based on a probe library (Roche NimbleGen SeqCap EZ Choice). Finally, the products were analyzed by NGS using the Illumina platform, MiSeq. Results indicated a deletion of exons 10–12 (EX10_12 del) in the 04006.2) , affecti by qPCR .After discharge from the hospital, the proband was on long-term treatment with a β-blocker, a diuretic, coenzyme Q10, and an angiotensin-converting enzyme inhibitor (ACEI). However, he required repeated hospitalization for heart failure, with gradually worsening muscle weakness, over the following 4 years. Finally, at the age of 26, he underwent orthotopic heart transplantation and has remained in good condition since transplantation.3.DMD gene located at Xp21.2  and LV assist device, as well as preparation for heart transplantation , myosin binding protein C3 (MYBPC3), LIM domain binding protein 3 (ZASP), tafazzin (TAZ/G4.5), desmin (DES), and others –16. 20%–DMD gene . It was DMD gene . In 2001antation . In DMD/antation , 23.To the best of our knowledge, this is the first case report of heart transplantation in a BMD patient with LVNC. With advances in the management of respiratory failure, heart disease has become the major cause of death in patients with muscular dystrophy . The priDMD gene (To date, there are no known mouse or cell culture models adequately reflecting the genotype. For decades the C57BL/10ScSn-Dmdmdx/J mouse has been the most commonly used model of DMD. However, BMD mouse models are rare. Previous studies have shown the feasibility of generating a DMD/BMD mouse model by exon deletion using CRISPR/Cas9 gene editing techniques , 29. ForIn conclusion, our 2 patients have provided new insights into the diagnosis, pathophysiology, genetic mechanism, and treatment of BMD patients with LVNC. We suggest that patients with BMD should be considered for early comprehensive cardiac evaluation to exclude LVNC, with the aim of preventing the development of severe end-stage heart failure.


Obstructive sleep apnea (OSA) syndrome is a very important sleep-related breathing disorder related to increased cardiovascular and overall morbidity and mortality. It is associated with multisystemic target organ damage due to micro- and macrovascular changes, resulting in carotid and coronary atherosclerosis, increased arterial stiffness, retinal damage, microalbuminuria, and cardiac remodeling. The latter consists of left ventricular (LV) hypertrophy, as well as diastolic and systolic dysfunction. The increasing burden of evidence shows that OSA also induces right ventricular (RV) remodeling that is more difficult to diagnose, but may also contribute to cardiovascular morbidity and mortality in these patients. Conventional echocardiographic parameters for assessment of RV systolic and diastolic functions are often not sensitive enough to detect subclinical and subtle changes in the RV function. Data published over last decade showed that the RV function, particularly systolic, is impaired in OSA patients and related with its severity. However, the introduction of speckle tracking echocardiography and the particularly longitudinal strain enabled the earlier detection of functional and mechanical changes even when conventional echocardiographic parameters of RV systolic function remained unchanged. The 3D echocardiography provided the possibility to evaluate the entire RV, with its unique shape, and determine 3D RV ejection fraction, which is comparable with results obtained by cardiac magnetic resonance. The use of this modality also provided a new insight into RV systolic (dys)function in OSA patients. In addition to weight loss, which has been proven very helpful in OSA patients, the only approved therapeutic approach is continuous positive airway pressure (CPAP) therapy. It is very important to assess if this therapy induces any improvement in cardiac structure and function. Limited data on this topic show that RV longitudinal strain is a more sensitive parameter rather than other conventional RV indexes in the detection of improvement in RV systolic function and mechanics. The aim of this review article is to summarize the current understanding of RV structural, functional, and mechanical changes in patients with OSA. Furthermore, we sought to provide the current knowledge regarding the effect of CPAP therapy on RV reverse remodeling in OSA patients. Obstructive sleep apnea (OSA) syndrome is the most frequent sleep-related breathing disorder that has been the most prevalent in middle age population of patients suffering from obesity, diabetes, and arterial hypertension. It has been related with changes in pulmonary circulation that result in right ventricular (RV) structural and functional changes, which may be related with poor outcomes in these patients ,2,3. OveStudies showed that patients with OSA experienced higher cardiovascular morbidity and mortality in comparison with the general population ,5, whichRV changes are the results of oxidative stress, inflammation, elevated increased sympathetic nervous activity, and consequently elevated blood pressure, both systemic and pulmonary. Furthermore, the high negative intrathoracic pressures have an unfavorable effect on pulmonary and systemic hemodynamics, mainly by increasing afterload . The remThe PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search for English-language articles published until December 2022. Studies were identified by using the following terms: “obstructive sleep apnea”, “sleep quality”, “sleep disordered breathing”,“cardiac damage”, “right ventricle”, “systolic dysfunction”, “global longitudinal strain”, ”right ventricular mechanics”, “echocardiography”, and “STE echocardiography”.The aim of this review article is to provide a summary of the current knowledge about RV structural, functional, and mechanical remodeling in patients with OSA, as well as the effect of CPAP on RV reverse changes in these patients.There are several mechanisms that can be responsible for changes in RV morphology, function, and mechanics in OSA patients. Many investigations reported permanently increased pulmonary pressure and even pulmonary hypertension in these patients. This may be related with chronic obstructive pulmonary disease, but also with cardiac comorbidities, such as left ventricular (LV) dysfunction and hypertension. Nevertheless, even in the absence of other known cardiopulmonary disorders, permanent pulmonary hypertension can develop in these patients , which cEarly data reported that RV dysfunction in OSA patients was related with daytime hypoxemia due to underlying lung disease , but recRV diameters are increased in OSA patients compared with control subjects in the majority of studies investigating the effect of OSA on RV remodeling ,17,18,19The evaluation of RV diastolic function and filling pressures are not frequently assessed in studies investigating OSA patients, and available data are conflicting . Peak eaThere is not much evidence about RA changes in OSA patients, and findings are conflicting. Some authors reported dilated RA in OSA patients ,25,28 anThe RA phasic function is a more comprehensive method for evaluation of RA remodeling, as it provides information about RA function during each part of the cardiac cycle. It has three phases: reservoir during ventricular systole, conduit during early ventricular diastole, and booster pump during late ventricular diastole . RA reseLi et al. investigated RA phasic function in OSA patients, using velocity vector imaging, and revealed no difference in reservoir function between patients with various level of OSA severity, whereas conduit function was lower and booster pump function was higher in patients with moderate and severe OSA comparing with controls . Early aDifferent parameters were used for the evaluation of the RV systolic function in OSA patients . ConventVitarelli et al. reported not only the reduction in TAPSE, FAC, and 3D RVEF in patients with moderate and severe OSA, but also a significant difference in 3D RVEF between OSA patients with and without pulmonary hypertension . HoweverThe meta-analysis that included a large number of OSA patients and evaluated all conventional parameters of RV systolic function  showed a significant increase in myocardial performance index and decrease in all other parameters, which only confirms the impairment of RV systolic function in OSA patients .The difference was also noticed when correlation between OSA severity, defined by AHI, and RV systolic function was investigated. Some studies reported a significant correlation and worse RV systolic function in patients with moderate and severe OSA ,25,30, wRV global and free-wall longitudinal strains represent parameters of RV systolic function and mechanics, which provide more information than conventional parameters  due to their higher sensitivity, specificity, reproducibility, and predictive value in a large spectrum of cardiovascular conditions ,8,9. TabInvestigations mostly agree about reduced RV GLS and free-wall LS in OSA patients ,30,31,33Some authors went so far as to investigate RV segmental changes in OSA patients, and interestingly found no difference in RV basal and apical free-wall LS, even though average free-wall RVLS was significantly lower in OSA patients . All sepRVLS shows a significant predictive value in the diagnosis of severe OSA (AHI > 30). Vitarelli et al. showed similar sensitivity and specificity of 3D RVEF and RVLS to detect severe OSA , whereasIt should also be noted that not all investigators documented a reduced RVLS in OSA patients. In a very specific population of OSA patients living at high altitude (1768 m above sea level) there was no difference in free-wall RVLS, TAPSE, s’, or 3D RVEF . The obtOur meta-analysis that included almost all aforementioned studies showed significantly lower RV GLS and free-wall RVLS in OSA patients compared with controls, as well as in patients with severe OSA in comparison to those with mild OSA . The metCPAP represents the most effective method for OSA treatment, usually in combination with dietary changes that are crucial for the reduction in body weight, which sometimes includes extreme procedures such as bariatric surgery. In addition to improv quality of life and some polysomnographic parameters, it is difficult to determine the level of improvement caused by CPAP. Novel echocardiographic parameters, primarily RV strain, can help the clinician in determining reverse cardiac remodeling .Vitarelli et al. showed that CPAP therapy after 4 months induced improvement in 3D RVEF, RV GLS, and free-wall RVLS, but not in TAPSE, FAC, and s’ . The AHIHammerstingl et al. showed that only apical free-wall RVLS significantly improved after 6 months of CPAP therapy, whereas other segments and RV GLS did not change . When apOur recent meta-analysis showed that CPAP did not significantly change TAPSE, but significantly improved RV GLS . SimultaOSA is associated with increased cardiovascular and overall morbidity and mortality, which is largely related to cardiac damage. The main issue is to diagnose these subclinical changes as soon as possible, as well as to detect cardiac improvement soon after CPAP therapy is initiated. An increasing body of evidence shows that conventional echocardiographic parameters are not sensitive enough, and new imaging parameters such as speckle tracking derived longitudinal strain have better sensitivity and predictive value in OSA patients. Therefore, RV GLS and particularly free-wall RVLS should be considered as additional parameters in the routine echocardiographic report in all OSA patients at the baseline, as well as during each follow-up visit. Additional analysis is necessary to determine its real clinical value, particularly its relationship with outcome in OSA patients. Naturally, these measurements should be performed along with complete LV echocardiographic assessment, including LV GLS. On the other side, patients with severe OSA often have comorbidities such as heart failure and/or atrial fibrillation, which can significantly impact the evaluation of RV (dys)function. It should be also acknowledged that even though treatment of OSA is recommended, large, randomized data that suggest a mortality benefit in these patients with treatment/CPAP use are still missing. This remains an important task for future investigation.RV longitudinal strain, both global and free-wall, represents a good parameter of subtle RV damage that can be detected before impairment of any other conventional echocardiographic index. Existing studies are very heterogeneous with regards to number of patients, age, BMI, OSA duration and comorbidities, and subjects in the control group. These are significant limitations in making a final conclusion about the effect of OSA on RV remodeling or influence of CPAP therapy on RV reversal remodeling. Large longitudinal studies with long follow-up are warrantied to provide missing information and answers on many raised questions regarding cardiac remodeling in OSA patients.


Breast radiotherapy (RT) induces diffuse myocardial changes, which may increase the incidence of heart failure with preserved ejection fraction. This study aimed to evaluate the early signs of diffuse fibrosis after RT and their evolution during a six-year follow-up.Thirty patients with early-stage left-sided breast cancer were studied with echocardiography and electrocardiography (ECG) at baseline, after RT, and at three-year and six-year follow-up visits. Echocardiography analysis included an off-line analysis of integrated backscatter (IBS). ECG was analysed for fragmented QRS (fQRS). In addition, cardiac magnetic resonance (CMR) imaging was performed at the six-year control. The left ventricle 16-segment model was used in cardiac imaging, and respective local radiation doses were analysed.Regional myocardial reflectivity in inferoseptal segments increased by 2.02 (4.53) dB (p = 0.026) and the percentage of leads with fQRS increased from 9.2 to 16.4% (p = 0.002) during the follow-up. In CMR imaging, abnormal extracellular volume (ECV) and T1 mapping values were found with anteroseptal and apical localization in a median of 3.5 (1.00–5.75) and 3 (1.25–4.00) segments, respectively. A higher left ventricle radiation dose was associated with an increased likelihood of having changes simultaneously in CMR and echocardiography .After radiotherapy, progressive changes in markers of diffuse myocardial fibrosis were observed in a multimodal manner in ECG and echocardiography. Changes in echocardiography and abnormal values in CMR were localized in the septal and apical regions, and multiple changes were associated with higher radiation doses.The online version contains supplementary material available at 10.1186/s13014-023-02319-z. Radiotherapy (RT) remains an essential part of cancer therapy despite remarkable advances in medical cancer treatment. Refinements in RT treatment protocols have reduced adverse effects on healthy tissue, but some direct radiation and scattering unavoidably affects nearby tissue. Breast RT induces slowly evolving fibrotic changes in cardiac structures, causing excess late cardiac morbidity and mortality , 2.The risk of heart failure with preserved ejection fraction (HFpEF) is increased 16-fold in breast cancer patients with prior RT compared to nonirradiated matched controls MyocardiThis single-centre prospective study included thirty eligible early-stage female left-sided breast cancer patients. The inclusion and exclusion criteria have been described previously in detail In additAfter surgery, all patients received adjuvant conformal 3D RT with modern RT techniques (3D-CRT). The treatment was delivered according to the institutional clinical guidelines. All patients underwent 3D computed tomographic treatment planning and were scanned under free breathing, as the voluntary deep-inspiration breath-hold technique (DIBH) was not implemented as clinical practice in our unit then. The radiation dose was either 50 Gy in 2 Gy fractions with an additional boost of 16 Gy in 2 Gy fractions to the tumor bed if clinically indicated or 42.56 Gy in 2.66 Gy fractions (hypofractionation). A mean heart dose constraint of 5 Gy was used in the treatment planning.The full details of treatment planning and contouring of the primary heart structures have been described previously . A dedicCardiac examinations were performed 6 ± 8 days prior to RT, within three days of completion of the RT, and three (2.5–3.3 years) and six years (5.7–6.2 years) after RT. Echocardiography was performed using a 1–5 MHz matrix-array X5-1 transducer. Baseline to three-year control examinations were performed with a Philips iE33 ultrasound machine . Due to the clinical update of equipment, the six-year control was performed using a Philips Epiq7 ultrasound machine . The off-line analysis of integrated backscatter (IBS) was performed using Philips Qlab version 13 . The IBS analysis is explained in Additional file 1: Figure A 12-lead ECG was recorded at each study visit. A visible notch in any part of the QRS complex in several consecutive beats was defined as a fragmented QRS (fQRS) . Cine-images were acquired using a balanced steady-state gradient echo (TrueFISP) sequence. All studies included standard long and short axis images. T1- and T2-mapping sequences were included in the standard protocol using a shortened Modified Look-Locker Inversion-recovery (ShMOLLI) sequence  for nonnormally distributed variables, or as numbers with percentages for categorical variables. The differences between groups were tested with the independent samples t-test or Mann–Whitney U test where appropriate. The differences in the measurements were tested with the paired samples t-test, Friedman’s test, Cochran’s Q test, or the Wilcoxon signed-rank test. Correlations were estimated using Spearman’s rank correlation coefficients. Multivariable linear regression analyses were performed to model the changes in fQRS, T1, ECV, and IBS values, adjusting the models with body mass index (BMI), hypertension, current smoking status, and mean left ventricle radiation dose. Binary logistic regression analysis was used to explain changes for groups formed based on the extent of abnormal imaging values. The analysis was performed with IBM SPSS Statistics software, version 27.0 for Windows . All p-values are two-sided. All p-values less than 0.05 were considered significant.The data are presented as the means with standard deviations (SD) for variables with normal distributions, as medians with quartiles (QThe baseline patient characteristics are shown in Table The mean heart radiation dose in the study population was 2.85 Gy (1.71–3.87 Gy). The mean heart dose was < 2 Gy in nine patients (30.0%), 2–4 Gy in 14 (46.7%), and > 4 Gy in seven (23.3%). The radiation doses varied remarkably between different left ventricle segments; please see Additional file 4: Table 2, 22.87 (7.31) mL/m2, 69.13 (7.04) %, and 48.53 (8.86) g/m2, respectively. In Table At six years, CMR-assessed left ventricle end-diastolic and end-systolic volumes, ejection fraction, and mass were within normal range: 73.53 (15.75) mL/mT1 mapping. The global median T1 was 1235 ms (1199–1273 ms). The incidence of abnormal T1 values (> 1300 ms) varied between segments, being most frequent in the apical and anteroseptal segments. Twenty-seven patients (90%) had at least one segment with abnormal T1 values (range 1–12). The median for number of abnormal segments was 3.00 (1.25–4.00), corresponding to 18.75% (7.81–25.00%) of the segments. In the multivariable analysis, hypertension predicted higher T1 values in apical segments .T2 mapping. The global median T2 was 35.54 ms (34.61–38.23 ms). Only two patients (6.67%) had abnormal values (> 60 ms) in any of the segments. One patient had abnormal values in two apical segments, the other in five basal segments.ECV mapping. The global ECV was 28.0% (26–30.2%). The incidence of abnormal ECV values (> 30%) varied between different segments, being most frequent in the apical and septal segments. In total, twenty-four patients (80%) had abnormal ECV values in at least one of the segments (range 1–13). The median number of abnormal segments was 3.50 (1.00–5.75), corresponding to 21.88% (6.25–35.94%) of the segments. In the multivariable analysis, hypertension predicted higher ECV values in apical segments .The change from baseline to six-year follow-up visit was measured with IBS analysis. The global IBS change was 1.04 (2.80) dB (p = 0.060). The most significant change was seen in inferoseptal segments, from 9.29 (3.35) dB at baseline to 11.76 (4.30) dB at six years (p = 0.026). Values were regarded as abnormal if they increased ≥ 100%. Twenty-three patients (77%) had at least one segment with abnormal IBS values (range 1–6). The median number of abnormal segments was 1.00 (1.00–3.00), corresponding to 6.25% (6.25–18.75%) of the segments. In the multivariable analysis, BMI  and hypertension  predicted IBS change when the whole left ventricle was assessed.Eighteen patients (60%) had fQRS in at least one lead (range 1–4 leads) at baseline. A spontaneous correction of some or all fragmentation changes was observed in twelve patients during the six-year follow-up.At six years, twenty-four patients (80%) had fQRS in one to five leads, including eight patients (26.7%) without fQRS at baseline. Novel changes (range 1–5 leads) were seen in twenty (66.7%) patients’ ECGs and the total percentage of leads with fQRS increased from 9.2 to 16.4% (p = 0.002) during the follow-up. Fourteen patients (46.7%) had new fragmentation at least in two different leads. For the distribution of changes, please see Fig. Patients were analysed based on whether they had more than one lead with a new fQRS during the six-year follow-up. The group with multiple new fragmentation changes (n = 14) had a statistically lower left ventricle radiation dose  and were less frequently hypertensive . A higher left ventricle dose was associated with fewer new fQRS in the multivariable analysis .Additional analyses were performed considering the extent of abnormal values in T1, ECV, and IBS in the different segments. There was no correlation between individual segmental or regional changes and RT doses. However, five patients (16.7%) had simultaneous abnormal values in T1, ECV, and IBS in the same segments. The patients with abnormal values in all three analyses had a higher left ventricle dose  than the rest, although this did not reach statistical significance. In the binary logistic regression analysis, increasing left ventricle radiation dose was associated with an increase in the likelihood of having changes in all three measurements .This multimodality imaging study showed that changes indicating diffuse myocardial fibrosis were progressive (IBS and ECG) during a six-year follow-up period, and they were localized in the RT-prone septal and apical segments in the echocardiography and CMR analysis. An association with radiation dose was seen when multiple parameters were combined.A key mechanism of RT-induced cardiotoxicity is the development of diffuse myocardial fibrosis HistologDiffuse fibrosis is commonly present in the early phases of several heart disorders, and the extent of fibrosis has been associated with the severity of clinical symptoms In fact,The role of CMR in oncology has been established, and growing evidence endorses the use of CMR in evaluating cancer patients receiving systemic cancer therapy CurrentlStudies of patient groups receiving chemotherapy and RT include lymphoma and breast, lung, and oesophagus cancer patients–17 It seIn our study, 90% and 80% of the patients (n = 27 and n = 24) presented abnormal segmental values in T1 and ECV mapping, respectively. The proportion of abnormal myocardial segments was 18.75% in T1 mapping and 21.88% in ECV mapping, a significant proportion concentrated in the apical and anteroseptal areas. As RT is known to induce diffuse myocardial fibrosis, our finding of changes indicating diffuse myocardial fibrosis in the areas of higher radiation dose is noteworthy. However, a dose relationship with a segmental radiation dose was not evident comparing single parameters, as has been the case in other studies , 15.While 36.7% of our patients had hypertension at baseline and an increase in the T1 and ECV values have been observed in hypertensive patients, this acts as a possible confounding factor. However, T1 and ECV elevation has been remarkable only among patients with co-occurring left ventricular hypertrophy, which was not present in our study population Besides Integrated backscatter measures myocardial reflectivity. The first studies showed increased values with histologically verified replacement scars Later stIn this study, all left ventricle segments were studied. A doubling of reflectivity was observed in 77% of our patients in at least one segment. Overall, 6.3% of the segments displayed a doubling of myocardial reflectivity, indicating the evolution of myocardial changes. Rising baseline BMI predicted a more significant change in left ventricle IBS values in our study. Obesity has been previously linked to higher IBS values, and it may predispose the heart to the cardiotoxicity of RT , 24.The presence of fQRS has been associated with abnormal myocardial activation and has been investigated in multiple cardiac diseases It has bKnowledge about fQRS after RT is scarce. In one study, Adar et al. . followeWe found an unexpected inverse association between new fQRS and radiation dose. Patients with multiple new fQRS also had hypertension less frequently, although this was not statistically significant. While it is counter-intuitive that a higher RT dose would cause fewer changes in the ECG, it can be speculated whether the hypertension medication protected patients from RT-induced cardiotoxicity, as we know that these medications hold cardioprotective qualities In additWe found an association with left ventricle RT dose in the situations where abnormal values were observed in the same segment with CMR (T1 and ECV) and echocardiography (IBS). This was most often seen apically and anteroseptally, where the high RT doses were delivered. However, no direct segmental level correlation was found. This might be due to various reasons, including imprecision between various imaging modalities considering the segmental data level. However, an association with the radiation dose was evident when the impact was high enough to simultaneously induce changes in the same segment in both CMR and echocardiography. It may be that milder impact was diluted by imaging inaccuracies, while only a more powerful effect with multiple changes produced an association with radiation heart doses.Our study endorses the results of previous studies indicating the evolution of diffuse myocardial fibrosis after RT , 13, 15 First, the study population was small and not powered enough to show a statistically meaningful correlation. Second, the results did not translate to clinically significant adverse events, most likely due to too short follow-up time. Third, there is evidence that cancer itself can cause changes in the myocardium shown by the CMR[Fourth, there were technical issues with the imaging. In contrast to CMR and echocardiography imaging, CT images were not ECG-gated or acquired with a breath-hold. This might have contributed to the missing segmental associations. In addition, we acknowledge that IBS is an angle-sensitive measurement also affected by depth. However, to overcome difficulties caused by angle and depth, a relative change in tissue reflectivity during the follow-up period was used instead.There are several limitations to be acknowledged. y the CMR This couDuring a six-year follow-up, multimodality imaging identified an accumulation of the markers indicating diffuse fibrosis in RT-prone regions of the left ventricle. An association with RT dose was found when multiple modalities were combined.Below is the link to the electronic supplementary material.Additional file 1: Figure S1. The integrated backscatter off-line analysis.Additional file 2: Figure S2. Fragmented QRS analysis example.Additional file 3: Figure S3. T1, T2 and extracellular volume (ECV) mapping in the CMR imaging.Additional file 4: Table S1. Mean and maximal radiation doses of left ventricle segments.Additional file 5: Table S2. Left ventricle segmental T1, T2, ECV, and IBS values.


Severe tricuspid valve (TV) regurgitation (TR) has been associated with adverse long-term outcomes in several natural history studies, but isolated TV surgery presents high mortality and morbidity rates. Transcatheter tricuspid valve interventions (TTVI) therefore represent a promising field and may currently be considered in patients with severe secondary TR that have a prohibitive surgical risk. Tricuspid transcatheter edge-to-edge repair (T-TEER) represents one of the most frequently used TTVI options. Accurate imaging of the tricuspid valve (TV) apparatus is crucial for T-TEER preprocedural planning, in order to select the right candidates, and is also fundamental for intraprocedural guidance and post-procedural follow-up. Although transesophageal echocardiography represents the main imaging modality, we describe the utility and additional value of other imaging modalities such as cardiac CT and MRI, intracardiac echocardiography, fluoroscopy, and fusion imaging to assist T-TEER. Developments in the field of 3D printing, computational models, and artificial intelligence hold great promise in improving the assessment and management of patients with valvular heart disease. Recently, an extended classification to “massive”  and “torrential”  has been proposed [Two-dimensional TTE also allows for an evaluation of the severity of TR. Severe TR may be identified through qualitative , semi-quantitative , and quantitative parameters (effective regurgitant orifice area (EROA) ≥ 0.40 cmproposed .Two-dimensional TTE also allows for left ventricle (LV) evaluation, RV assessment , and pulmonary hypertension (PHT) diagnosis and classification .Three-dimensional TTE allows for an evaluation of all three TV leaflets at the same time  and to sThe three-dimensional TTE TV acquisition protocol includes an apical four-chamber view with and without Color and a parasternal RV-inflow view with and without Color; the TV en face view should locate the septal leaflet and the interatrial septum in the 6 o’ clock position, the posterior leaflet to the left, and the anterior leaflet and aorta to the right ,23. To vThese assessments are necessary for pre-procedural screening to select eligible patients for transcatheter TV repair, following the echocardiographic exclusion criteria of the CLASP TR easy feasibility study (severe LV dysfunction with LV ejection fraction (LVEF) < 30%, severe RV dysfunction, coaptation gaps > 10 mm, leaflet length < 8 mm), the TRILUMINATE PIVOTAL trial , or common for both of them . This first screening allows for the identification of the correct intervention timing and avoids futile procedures ,16,24.The anatomical assessment of the TV is better studied through two-dimensional (2D) and three-dimensional (3D) transoesophageal echocardiography (TEE), which is key to obtain a detailed functional valve anatomy, necessary to assess repairability. Anteroseptal jet location, a small septolateral gap (≤7 mm), and trileaflet TV morphology are the favorable anatomical features to perform leaflet approximation strategy; a septolateral coaptation gap between 7–8.5 mm and a posteroseptal jet location are considered feasible but suboptimal anatomical characteristics to perform . A comprThe main pre-procedural two-dimensional TEE views firstly include mid-esophageal (ME) views, where the TV is in the far field and the annular plane cannot be aligned perpendicular to the ultrasound beam. An ME four-chamber view at 0° allows for a visualization of the septal leaflet adjacent to the septum and the anterior or posterior leaflet on the other side, which can be clarified using biplane imaging. An ME RV inflow-outflow view at 50–60°, also defined as the “TV commissural view”, images the anterior leaflet adjacent to the aorta and the posterior leaflet opposed, and with biplane imaging we can visualize the septal leaflet as well . TV commConsidering the TV anatomic variability, 3D imaging is crucial for pre-procedural planning as it has higher accuracy in the identification of the number and location of the leaflets. Leaflets identification is based on the surrounding anatomy, with the aorta adjacent to the anteroseptal commissure and the coronary sinus adjacent to the posteroseptal commissure. A 3D en face TV view is acquired from the 2D commissural view and may be realized in two different orientations: with Z rotation (180° rotation) to obtain a “surgeon’s view” with aorta and anterior leaflet on top , or withThree-dimensional echocardiography also has a prognostic role; indeed, impaired pre-procedural three-dimensional echocardiographic-derived RVEF ≤ 45% has been associated with increased all-cause mortality at 1-year follow up after tricuspid TEER .Although the relevance of cardiac computed tomography (CCT) imaging in patient screening and the pre-procedural planning of transcatheter TV treatments is less well established compared to echocardiography , it has To maximize image quality, a specific CT acquisition protocol with right-sided opacification  is recomCCT may provide useful information on TV and leaflet anatomy, the valve gap, mechanisms of TR, and the best fluoroscopic angles for coplanar alignment and leaflet grasping strategy ,34.Using the multiplanar reconstruction, a short-axis plane can be reconstructed on the annular level starting from RV two- and four-chamber views ; this alAdditional MPR planes parallel to the TV can optimize the visualization of the TV leaflets anatomy and identification of a four-leaflet configuration variant, which is associated with an increased risk of residual TR, especially in patients with a wide coaptation gap or TR jet from the posteroseptal or anteroposterior commissures . It alsoCCT can also provide useful information on the right chambers, such as right ventricular and right atrial volumes , as wellFurthermore, CT can assess peripheral vessels in terms of suitability of access and route to the heart. Indeed, CT can be used to analyze the measurements of the inferior vena cava, as well as the size of the femoral veins, which are used to deliver the sheaths and the devices to their target ,27.Finally, CCT can predict the ideal fluoroscopic projections to be intra-procedurally used and generate projection images, which can be exported and used to support intraprocedural fluoroscopy with fusion imaging for guiding treatments, which is critical for reducing procedure times and radiation exposure .X-ray exposure remains the main disadvantage of CCT, although the newest generation of CT scanners allow for substantially shorter scan times, lower radiation doses, and less iodinated contrast utilization .Cardiac magnetic resonance (CMR) is not the first line imaging modality, but given its excellent spatial resolution, it has an additive value to 3D echocardiography for both anatomic and functional assessment of the TV, TA, and right-sided chambers ; it can CMR is useful to assess the severity of regurgitant TV lesions in patients with inadequate echocardiographic quality or discrepant results; it represents the reference method for the evaluation of RV volumes and function allowing for an evaluation of the consequences of TR ; finallyTR severity can be assessed by CMR using indirect  as RV stroke volume- forward pulmonic flow volume or TR fraction (TRF) as TR volume/RV stroke volume ×100) or direct methods (by effective regurgitant orifice area measurement) . No specPre-procedural CMR-quantified RVEF and RV end systolic volume indexes were independently associated with increased postoperative cardiac death and major cardiac events in patients with isolated severe TR undergoing corrective surgery . BaselinCMR also allows for a non-invasive measurement of the pulmonary vascular resistance (PVR), which may help improve the selection of candidates for tricuspid interventions since patients with end-stage RV failure may present reduced pulmonary artery pressure but higher PVR .Finally, myocardial fibrosis detection by CMR has a prognostic implication for RV failure and may be useful to define the optimal timing of interventions in patients with severe TR .ME and DE RV inflow/outflow views  and TG views are the main views for the intraprocedural guidance of tricuspid transcatheter repair by coaptation devices ; the maiThe first step is represented by the introduction and advancement of the delivery system into the right atrium (RA), guided by the bicaval view with biplane imaging . For theThe role of TTE during the procedure is generally limited, since TEE allows us to continuously follow the procedure with less exposure of the structural imager to the radiations, although TTE may be useful in the case of an intraprocedural complication assessment, such as pericardial effusion .The idea of using catheter-based devices to image the cardiac structures dates back to the 1960s , but theFor intraprocedural guidance of TV transcatheter repair, ICE is particularly useful in patients with low quality TEE imaging , which iUntil recently, the use of ICE for structural heart procedures has been limited by the presence of only 2D imaging planes, lower color Doppler quality, and volume size capability, and by the need for considerable catheter manipulations to visualize the target cardiac structures . EnhanceA complementary approach using both TEE and ICE imaging with 4D catheters has been shown to be useful during T-TEER. Indeed, ICE can overcome TEE acoustic shadowing from the clip delivery system, facilitating leaflet grasping and confirmation of leaflet insertion and mobility , which mDespite the superb ability of ICE to visualize the tricuspid apparatus and the RV, current limitations for its use for intra-procedural guidance of tricuspid transcatheter interventions are represented by the presence of limited published data on guidance for TV interventions and by the operator learning curve; additionally, there is limited reusability for ICE catheters, with increased costs compared with TEE, and a higher risk of complications related to the additional access site and catheter manipulation. Finally, there is also a lack of standardization regarding ICE imaging acquisition, interpretation, reporting, and related society guidelines .Fluoroscopy represents a key imaging modality for the intraprocedural guidance of transcatheter TV procedures , since TWhile fluoroscopy is a 2D planar imaging modality affected by parallax and requiring multiple viewing angles to obtain accurate 3D spatial data, multi-slice computed tomography (MSCT) is not affected by parallax and allows preserved spatial resolution in all imaging planes . MSCT muFour main fluoroscopic projections are described for the right chambers. The right heart one-chamber short axis view is obtained by placing the C-arm in a left anterior oblique view or “LAO” with a variable degree of caudal angulation (average LAO 55°/CAU 15°); it shows the “enface” view of the TV seen from the RV side, mimicking the 3D echo “enface” view, and is used to navigate the catheter to the target structure; it also visualizes the trajectory of the right coronary artery and its distance from the TA, as well as the trajectory of the coronary sinus ,62,63. TInterventional imagers and interventionalists usually have to mentally combine complementary data from multiple imaging modalities for intraprocedural guidance; in addition, data from different modalities are generally imaged from different perspectives and are therefore displayed in different orientations, and each modality presents different limitations . EchocarFusion imaging systems combine CCT, CMR, or echocardiographic images (from TEE or ICE) with fluoroscopy, creating a multi-modalities image overlay on a single screen  that oveIn order to create hybrid images, it is necessary to utilize compatible same-brand equipment and specialized hardware and software . Static The benefits of fusion imaging have been shown for some structural transcatheter procedures, such as a reduced procedure time for transeptal puncture for either MitraClip or left atrial appendage closure , a decreIn the future, the development of more advanced fusion approaches such as a combination of CT, fluoroscopy, and echocardiography all together may further improve intraprocedural navigation.Echocardiography represents the first and key modality by which to assess the efficacy and durability of transcatheter TV repair interventions.As T-TEER has only recently emerged as a widespread therapeutical approach, there is no standardized timing for postprocedural follow-up. However, most sites endorse outpatient evaluation at 1, 6, and 12 months after the procedure , followed by annual re-evaluation, in the case of procedure success . The echDue to the anterior position of the TV apparatus, 2D and 3D TTE echocardiography is non-inferior to TEE evaluation; usually, 2D TTE provides all the necessary information to obtain a global evaluation of the right-heart structures and follow outcomes after TV percutaneous repair. It is important to assess the grade of residual TR, to confirm the correct positioning of the device/s, and to evaluate signs of reverse remodeling of the TV apparatus  and of the RV, and changes in RV function . The thrFirstly, one should focus on the device in order to ensure appropriate leaflets insertion, arms stability, and orientation: the device must be oriented perpendicularly to the coaptation line of the selected leaflets, and this can be particularly appreciated with the 3D zoom en face view of the TV ,76. DoppIn case of suspicion of complications, such as device detachment, loss of leaflet insertion, leaflet tears, or active endocarditis, 2D and 3D TOE evaluation is mandatory.Finally, post-procedural tricuspid annulus remodeling and right ventricular-pulmonary arterial (RV-PA) coupling and afterload reserve should be evaluated, as they may have a long-term prognostic relevance; a decline in the RV-PA coupling ratio (measured by dividing pulmonary artery systolic pressure by TAPSE obtained by TTE) is independently associated with a lower risk of all-cause mortality during the first year after TTVR, and is more frequent in patients with a high baseline RV-PA coupling ratio, although additional studies are needed for validation ,80.The role of cross-sectional imaging for follow-up evaluation after T-TEER still has to be defined and certainly represents a promising area for future growth .Currently, cardiac CT plays a role during follow-up mainly in cases with dubious findings with the first line imaging modalities regarding tricuspid apparatus/device evaluation or the presence of potential complications ,81. IndeSerial CMR assessment of the right heart chambers size, volumes, and function may also be helpful to determine responses to TV transcatheter therapy and might have a role in predicting clinical outcomes ,83.The application of new technologies to echocardiographic valvular assessment is growing and has the potential to play a pivotal role considering the fast-increasing development of these new tools, the growing volume of patient data, and the issue of clinical time restrictions.The use of 3D printing has recently increased to reach a wide range of medical applications and, in the field of heart valve disease, it might address many of the present challenges, such as patient selection, prosthesis choice and sizing, and innovation in valve design . In factDevelopments in the field of artificial intelligence (AI) hold great promise too in improving the assessment and management of patients with valvular heart disease. In fact, AI may improve the acquisition and processing of echocardiographic images, as has already been demonstrated . Commerc


Studies over recent years have redeveloped our understanding of uremic cardiomyopathy, defined as left ventricular hypertrophy, congestive heart failure, and associated cardiac hypertrophy plus other abnormalities that result from chronic kidney disease and are often the cause of death in affected patients. Definitions of uremic cardiomyopathy have conflicted and overlapped over the decades, complicating the body of published evidence, and making comparison difficult. New and continuing research into potential risk factors, including uremic toxins, anemia, hypervolemia, oxidative stress, inflammation, and insulin resistance, indicates the increasing interest in illuminating the pathways that lead to UC and thereby identifying potential targets for intervention. Indeed, our developing understanding of the mechanisms of UC has opened new frontiers in research, promising novel approaches to diagnosis, prognosis, treatment, and management. This educational review highlights advances in the field of uremic cardiomyopathy and how they may become applicable in practice by clinicians. Pathways to optimal treatment with current modalities  will be described, along with proposed steps to be taken in research to allow evidence-based integration of developing investigational therapies. Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD), ahead of even end-stage renal disease (ESRD) . While tThese conflicting definitions have made it challenging to precisely define the size of this patient population worldwide, but reports from the USA estimate that 2 million people in that country alone will require dialysis for ESRD by 2030  and thatAmong those patients with ESRD, cardiovascular disease is the cause of approximately half of deaths , and an Established risk factors associated with the development of UC include hypertension, hyperlipidemia, and diabetes, which are also well-known risk factors for atherosclerotic disease . UC alsoHowever, other more specific potential risk factors for UC have been identified, including uremic toxins, anemia, hypervolemia, oxidative stress, inflammation, insulin resistance, and CKD-mineral and bone disorder (MBD) . ContinuThe topics covered in this review are aimed at providing an overall understanding of UC Fig. , particuUC was first described by Bailey et al. in 1967 . From thThe definition of a typical time duration for the development of UC after the onset of CKD is difficult because of the lack of a firm definition or threshold for UC. However, the disease process itself becomes evident in the early stages of CKD, at relatively preserved estimated glomerular filtration rates .As the field progresses, researchers should take care to identify any potential differential or atypical patient subsets in whom UC may develop differently. In children and adolescents with CKD, for example, there is typically no clinical background of pre-existing cardiac disease, although the risk of cardiovascular death is similar to that in adults with CKD . The impRegardless of patient type or stage of development, the pathogenesis of UC is clearly multifactorial, involving multiple pathways including circulating uremic toxins, mineral metabolism, insulin resistance, and eventually hemodynamic overload. These pathways contribute to the increased left ventricular (LV) mass common in CKD and attributable to both myocyte hypertrophy and an expansion of the interstitial space caused by DIF .A deficiency in carnitine, an important factor in the oxidation of fatty acids, is postulated to play a role in insulin resistance and the development of UC, on the basis of observations in patients undergoing dialysis . InsulinThe process of cardiac metabolic remodeling in patients with CKD is characterized by various forms of cardiac metabolic maladaptation including altered mitochondrial function, myocardial substrate utilization, metabolic transporter function and expression, and impaired insulin response and phosphoinositide-3 kinase-AKT signaling, leading to impaired cardiac function . These mUremic toxins, by definition uremic retention solutes that impede normal organ function, represent another pathway leading to UC and include P-cresyl sulfate (pCS), β2-microglobulin, indoxyl sulfate, and homocysteine . Many ofAdditionally, certain monocyte/macrophage subsets have been shown to be positively or negatively associated with cardiovascular calcification, an important predictor of CVD, in patients with CKD . The infOne of the most promising areas of understanding UC is the recent progress in understanding the role of low serum levels of Klotho and elevated serum levels of FGF-23, both regulators of phosphate metabolism, in the development of LVH . Klotho,Importantly, none of the established treatments for CKD directly targets the metabolism of the uremic heart, implying a potential area for the development of new treatments.Because of the heterogeneous nature and involvement of multiple systems in UC, current clinical methods for its diagnosis involve multiple modalities.Electrocardiogram (ECG) is the most widely available, least invasive, and least expensive method for assessing LV dysfunction and identifying volume and pressure abnormalities in patients with CKD. ECG changes that are characteristic or indicative of UC include the presence of Q waves, ST segment changes, prolonged QRS intervals, and tachycardia . AssociaAs summarized in Table Transthoracic echocardiography (TTE) is a readily available, inexpensive, and noninvasive modality offering detailed observation of cardiac structures and potential abnormalities, particularly LVH. TTE is a well-established method to assess LV mass, commonly used to provide prognostic information or as an endpoint in studies of CVD risk. However, these methods involve indirect calculation of LV mass rather than direct observation of the actual measurements, and a large meta-analysis showed no clear association between changes in LV mass and CV mortality in patients with CKD , limitinCardiac computed tomography (CT) scanning can be used in UC, for example, to define areas of myocardial fibrosis . This isCardiac MRI (cMRI) can be used to provide information on multiple cardiac structural and functional parameters including coronary arterial flow, perfusion, myocardial scarring, and interstitial fibrosis . cMRI isAdditionally, there has been some research into the use of PET in the setting of CKD to evaluate myocardial perfusion and identify infarcted areas, as well as to assess coronary flow reserve  and areaEach of these imaging methods has some limitations in diagnosing or predicting UC, particularly in differentiating UC from other cardiomyopathies. However, these methods continue to evolve and become more practical and specific.Continuing advances in imaging have led to promising techniques for improved diagnosis of UC. For example, the fibrotic process can now be observed on cardiac MRI by T1 mapping, a technique that quantifies the relaxation time of protons on inversion recovery prepared images  times) by using analytical expression of image-based signal intensities . FibrotiThese cardiac MRI T1 and T2 (transverse relaxation time) mapping techniques can be used to characterize myocardial involvement in CKD, with higher scores related to worsening clinical status and myocardial damage  In other developments in cardiac MRI, the feature-tracking analysis technique involves a post-processing algorithm that uses a block-matching approach to assess the movement of specific anatomical features and identify longitudinal strain throughout the course of the diastole and systole . A newerNew and more useful quantification measures are being developed along with the abovementioned novel imaging techniques. For example, global longitudinal strain  has been reported to be a more sensitive predictor of myocardial dysfunction in ESRD compared with LVEF .One obvious step to further advance screening and diagnosis procedures in the clinic would be to identify and quantify risk factors for UC and to apply that information to develop a predictive scoring system. This will be challenging because, compared with other cardiomyopathies, there are probably few findings that are specific to UC. To date, unfortunately, not enough is known about the use of existing or emerging diagnostic biomarkers or other means of detecting asymptomatic patients who may be at high risk for UC. The establishment of specific imaging methods should also be a priority. Echocardiography and MRI are the most promising noninvasive modalities.In addition to developing the means to diagnose UC, in general practice, it will be important to detect ischemic changes early, based on their association with CKD, using ECG, echocardiography, chest X-ray, or coronary artery CT. This means that cardiac function should be screened and followed up from the early stages of CKD. In age-related decline in cardiac function, diastolic dysfunction is generally accepted to appear prior to systolic dysfunction. Echocardiography is the preferred modality for this identification, but as mentioned above, ischemic changes may also be detected by ECG. For patients who are already showing typical symptoms of cardiomyopathy, it may be too late to implement interventions that could change the clinical course.Significant clinical experience has shown that UC is closely associated with CKD and that cardiac function declines over time in patients with CKD. The most common cause of this decline is ischemic heart disease. Therefore, if coronary artery stenosis is observed, revascularization procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) may be performed, with resulting improvement in cardiac function. However, myocardial injury in UC is likely to extend beyond myocardial ischemia to endothelial damage in the microvasculature and cellular-level damage, as well as to the development of myocardial fibrosis. There is sufficient overlap between ischemic cardiomyopathy and UC to make it clinically difficult to distinguish between these two conditions, although it is important to treat UC when it cannot be explained as ischemic cardiomyopathy. To date, however, there is no specific treatment for UC, and the utility of current treatments may be insufficient at this point. Clarification in this area will be an important future issue for both diagnosis and treatment.In terms of advances that can easily and immediately be adapted to the clinic, it is important to note that in no area related to UC does there already exist a sufficient evidence base to adopt new procedures based on current knowledge. For this reason, filling the knowledge gaps will be of critical importance.This section will discuss the application of new findings in the therapeutic management of UC, the monitoring of disease progression, and the overall efficacy of available treatment. Current available care options, the limitations thereof, and the potential of new therapeutics are presented in Table Current options for pharmacotherapy for patients with UC include many therapies used for heart failure in general. In particular, these include ACE inhibitors and angiotensin receptor blockers, which have been shown to reduce the progression of renal and vascular damage in patients with CKD ; carvediRegardless of pharmacotherapy, the eventual treatment for UC in most cases is renal replacement therapy, which can be accomplished by hemodialysis, peritoneal dialysis, or renal transplantation.Hemodialysis has been shown in many studies to potentiate reverse cardiac remodeling and to reverse some of the clinical sequelae of UC . This isPeritoneal dialysis is a home therapy that may represent a preferable treatment option for some patients versus hemodialysis, as it does not require patients to travel 3–5 times a week to a dialysis center and may even be carried out while the patient is sleeping. Costs may also be lower than those for dialysis, depending on the treatment setting. However, there may be greater risk of treatment discontinuation with peritoneal dialysis because it is self-administered, and some studies suggest that if not adequately monitored, patients undergoing treatment via this modality appear to have worse CV outcomes, including increased LV mass index, in the long term  .Finally, renal transplantation confers a significant survival advantage versus other treatment modalities, as well as long-term improvement in LVEF and reduction in LVH . These aSalvia miltiorrhiza Bunge (red sage), which is widely used as an herbal medication in traditional Chinese medicine. A recent study using a rat model of UC  reported efficacy in reducing cardiac hypertrophy, edema, inflammation, and fibrosis [Beyond these existing treatments, new and experimental therapies offer the potential for superior outcomes. Among these is a potential role for salvianolic acid B , the active component in fibrosis .The role of recombinant human erythropoietin (EPO) administration in the treatment of anemia in CKD has been explored with controversial results. Initial studies in anemic patients undergoing dialysis showed improved quality of life and reduced need for transfusions; the use of erythropoiesis-stimulating agents (ESAs) subsequently became widespread. However, some recent studies have indicated an increased risk of stroke without a survival benefit . It appeThe role of vitamin D supplementation in this population is also being explored, with some positive findings in terms of LV fiber shortening . IntraveFurther research is clearly needed to address the gaps in the literature regarding the etiology, diagnosis, and management of UC. This section describes the shortcomings in the current understanding of UC and offers suggestions for the types of prospective or retrospective research that could be carried out to address these gaps. There is an overall lack of research in this population in general; for example, many trials of therapies aimed at reducing CV risk have systematically excluded patients with CKD. As a result, there is a relative paucity of specific data, with much research focusing either on all patients with CKD or all those with heart failure.A promising area for research is that related to the cardiac effects resulting from the interplay of FGF23 and Klotho . If thisThe contributions of inflammation and systemic oxidant stress should be further explored, especially as oxidative stress appears to play some role in the molecular pathways postulated to be associated with the development of UC via myocyte hypertrophy and DIF causing expansion of interstitial spaces .Besides these specific factors, research should be aimed at improving detection and treatment and at addressing the limitations of current methods, as noted above. There is a gap between the understanding of the underlying pathomechanisms and the development of actual treatments (including pharmacotherapy). In other words, we can diagnose the disease, but there are virtually no specific treatment options for UC. The potential and emerging modalities identified in Table The research to date has been essential in forming the modern understanding of the etiology, pathogenesis, diagnosis, and treatment of UC. However, this improved understanding has not yet led to applicable modifications to practice for the treating clinician, apart from substantial improvements in imaging technology. Innovative research must take place to fill these gaps in current research. Differential diagnosis, risk quantification and stratification, and specific treatment options for UC are important areas where research must transform our current understanding into applicable tools for the clinician. Clinicians, institutions, and organizations must work toward furthering the science and acting on it to improve patient outcomes in this disease that has such a significant global burden.


Little is known about the characteristics of arterial stiffness in heart failure (HF). This study was performed to compare the degree of arterial stiffness and its association with left ventricular (LV) diastolic function among three groups: control subjects, patients with HF with reduced ejection fraction (HFrEF), and patients with HF with preserved ejection fraction (HFpEF).A total of 83 patients with HFrEF, 68 patients with HFpEF, and 84 control subjects were analyzed. All HF patients had a history of hospitalization for HF treatment. Brachial-ankle pulse wave velocity (baPWV) measurement and transthoracic echocardiography were performed at the same day in a stable condition.P < 0.05 for each). After adjustment of age, baPWV values were similar between patients with HFrEF and HFpEF (P = 0.948). In the multiple linear regression analysis, baPWV was significantly associated with both septal e′ velocity  and E/e′ . However, baPWV was not associated with either of the diastolic indices in HFrEF group. The baPWV was associated only with septal e′ velocity  but not with E/e′ in the HFpEF group in the same multivariable analysis.The baPWV was significantly higher in patients with both HFrEF and HFpEF compared to control subjects (1,661 ± 390, 1,909 ± 466, and 1,477 ± 296 cm/sec, respectively; Although arterial stiffness was increased, its association with LV diastolic function was attenuated in HF patients compared to control subjects. The degree of arterial stiffening was similar between HFrEF and HFpEF.The online version contains supplementary material available at 10.1186/s40885-022-00233-2. Heart failure (HF) is a terminal state of almost all heart diseases, and its prevalence continues to increase with age. Mortality and medical costs due to HF are so enormous that they pose a huge burden to our human society , 2. TherHF is divided into HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) according to left ventricular ejection fraction (LVEF) . AlthougThis study is a cross-sectional study conducted at a general hospital in a large city . The study was conducted in accordance with the Declaration of Helsinki. The study protocol was reviewed and approved by the Institutional Review Board of Seoul Metropolitan Government Seoul National University Boramae Medical Center (No. 10–2020-313). Written informed consent was obtained for prospectively enrolled subjects and informed consent was waived by Institutional Review Board for retrospectively enrolled subjects.In the HF groups, the eligible study subjects were patients who had a history of hospitalization for the management of new-onset acute HF or acute exacerbation of chronic HF. At the time of hospitalization, the main diagnosis should be HF. HF patients with LVEF < 40% were further stratified as the HFrEF group, and HF patients with LVEF ≥ 50% were further stratified as the HFpEF group . Relativ2). Systolic and diastolic blood pressures were recorded at the time of study enrollment using an oscillometric device. Information on cardiovascular risk factors including hypertension, diabetes mellitus, dyslipidemia, cigarette smoking status, coronary artery disease (CAD), and stroke were obtained. Hypertension was defined basis on previous diagnosis, the current use of antihypertensive medications used to control blood pressure, or blood pressure ≥ 140/90 mmHg. Diabetes mellitus was defined based on previous diagnosis, the current use of antidiabetic medications used to control hyperglycemia, or fasting blood glucose ≥ 126 mg/dL. Dyslipidemia was defined based on previous diagnosis, the current use of antidyslipidemic medications used to control dyslipidemia, or low-density lipoprotein cholesterol ≥ 160 mg/dL. Smokers were defined as those who had smoked during the past year. CAD included myocardial infarction and coronary revascularization. Stroke was defined as a sudden neurological abnormality with cerebral infarction or hemorrhage in imaging studies. After overnight fasting, venous blood was drawn and the blood levels of the following laboratory parameters were obtained: white blood cell count, hemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, creatinine, glucose, glycated hemoglobin, and C-reactive protein. Estimated glomerular filtration rate was calculated by the Modification of Diet in Renal Disease study equation. Information on concomitant cardiovascular medications including calcium channel blockers, beta blockers, renin-angiotensin system blockers, statins, and diuretics was also obtained.Body mass index was calculated as weight in kilograms divided by the square of height in meters (kg/m3 – (LV end-diastolic dimension)3] + 0.6. LV mass index was calculated as LV mass / body surface area. In apical four-chamber view, peak velocities of E and A waves of mitral inflow during diastole were obtained using a pulsed wave Doppler, and E/A ratio was calculated. Deceleration time of E wave was also measured. Using the tissue Doppler imaging technique, the peak velocity of mitral septal annulus (e′) was obtained. Left atrial (LA) volume was measured using the biplane disk summation method and indexed to body surface as LA volume index. In modified four-chamber view, the maximal velocity of tricuspid regurgitation (TR Vmax) was obtained using the continuous Doppler method. In this study, we focused on sepal e′ velocity and E/e′ as indicators of LV diastolic function because these indicators are relatively easy to measure and reliable indicators that are recommended first for the evaluation of left ventricular diastolic function [Transthoracic echocardiography was performed using commercially available machines . Echocardiography was performed according to standardized protocols based on current guidelines’ recommendations , 17. LV function .Arterial stiffness was assessed using baPWV. The baPWV was measured noninvasively using a volume-plethysmography device  in the supine position 5 to 10 min after resting in an independent space in a quiet state , 20. On P < 0.05. All statistical analyses were performed with the statistical package IBM SPSS ver. 23.0 .Continuous variables were expressed as mean ± standard deviation and categorical variables were expressed as number (%). Comparisons among three groups  were performed using analysis of variance (ANOVA) for continuous variables and chi-square test for categorical variables. Bonferroni post-hoc analysis was applied to compare the baPWV mean difference between the two groups. The difference in baPWV among the three groups was further compared by correcting for age through the analysis of covariance (ANCOVA). Linear relations between baPWV and diastolic parameters were assessed using Pearson correlation analysis. Scatter plots demonstrated these correlations. To find independent association between echocardiographic diastolic indices and baPWV, multiple linear regression analysis was performed. The following potential confounders were controlled during multivariable analysis: age, sex, and cardiovascular risk factors including hypertension, diabetes mellitus, and dyslipidemia, and smoking status. All analyses were two-tailed, and clinical significance was defined as Comparisons of clinical characteristics among three groups are shown in Table Results of transthoracic echocardiography are demonstrated in Table P < 0.001). In post-hoc analysis, baPWV value was significantly higher in patients with HFrEF than in control subjects (P = 0.006). Also, baPWV value was significantly higher in the HFpEF group compared to the control and HFrEF groups (P < 0.05 for each). Differences in baPWV values between the control group and HFrEF or HFpEF groups were also significant when age-adjusted using ANCOVA analysis . However, after adjusting for age, no difference in baPWV values was observed between the HFrEF and HFpEF groups . Without stratification by heart failure type, baPWV was significantly higher in heart failure group than in control group  even after controlling for age  . baPWV was significantly correlated with E/e′ in control group , but not in the HFrEF  and HFpEF groups . Without stratification by heart failure type, baPWV was significantly correlated with septal e′ velocity  but not with septal E/e′   and E/e′  even after controlling for clinical confounders in the control group. However, baPWV was not associated with septal e′ velocity  and E/e′  after controlling for confounders in the HFrEF group. The baPWV was associated with septal e′ velocity  but not with E/e′  in the HFpEF group in the same multivariable analysis. Without stratification by heart failure type, baPWV was independently associated with septal e′ velocity  but not with E/e′   baPWV was significantly higher in patients with HFrEF and HFpEF compared to control subjects; (2) although univariable comparison showed that baPWV was significantly higher in patients with HFpEF than in those with HFrEF, it was similar between patients with HFrEF and HFpEF after adjusting for age; and (3) baPWV was significantly associated with septal e′ velocity and E/e′ in the control group, had no association with either of the LV diastolic indices in patients with HFrEF, and was associated only with septal e′ velocity, but not with E/e′ in patients with HFpEF.Our results showed that baPWV was significantly higher in patients with HF than in control subjects who had no HF or other documented cardiovascular disease and stroke. The significance of this difference remains even after adjusting for age, a major determinant of arterial stiffness. It may be due to the fact that patients with HF had more various risk factors that could increase arterial stiffness compared to the control group, which was consistent with the characteristics of our study population. We also presented, for the first time, differences in the degree of arterial stiffness according to HF types. Although the baPWV value in the univariable comparison was higher in the HFpEF group than in the HFrEF group, there was no difference between the two groups after age adjustment. Large-scale data are required to verify our findings.As arterial stiffness increases, LV diastolic function deteriorates. In a stiffened artery, the velocity of reflected wave is increased and merges with the forward wave early . This raIn the comparisons between control and HF groups, our results showed that the degree of arterial stiffness is more severe in the HF groups, but the association between arterial stiffness and LV diastolic function was stronger in the control group. This implies that arterial stiffness has a greater impact on the diastolic function of LV in the stage before the HF onset, and that the effect is somewhat weakened when HF has already occurred. Therefore, this may suggest that strategy targeting arterial stiffness to improve LV diastolic function or prevent HF  should bOur study has several limitations. First, the associations of baPWV with septal e′ velocity and E/e′ were determined with cross-sectional data; therefore, the causal relationship between arterial stiffness and diastolic function could not be confirmed. Second, although carotid-femoral pulse wave velocity (cfPWV) is the gold standard for the non-invasive measurement of arterial stiffness , baPWV wCompared to the control subjects, arterial stiffness was increased in HF patients, but the association of the arterial stiffness on LV diastolic function was weaker in HF patients compared to the control subjects. These results suggest early detection and effective intervention for reverse arterial stiffening may limit adverse cardiac remodeling and HF. The degree of arterial stiffness was similar between HFrEF and HFpEF, but the association between arterial stiffness and LV diastolic function was stronger in the HFpEF group. Given that baPWV correlated well with septal e′ velocity in HFpEF, septal e′ velocity could be useful for devising a therapeutic strategy targeting VA coupling. Further large-scale studies are needed to confirm our findings.Additional file 1:Supplementary Figure S1. The difference in baPWV between control and HF group. baPWV was significantly higher in HF patients than in control subjects. Supplementary Figure S2. Associations between baPWV and LV diastolic parameters in control and HF group. The associations of baPWV with septal e′ velocity and septal E/e′ were stronger in control subjects than in HF patients. Supplementary Table S1. Independent association between brachial-ankle pulse wave velocity and left ventricular diastolic parameters.