The GRS and GCS of the left and right ventricles showed a moderate correlation in the PAH group . PAH patients with preserved RV function (n = 9) showed significantly decreased global and segmental RS, CS, and LS of the right ventricles than healthy controls , except for basal RVGCS . Only the LVGLS was significantly different between the PAH patients with preserved LV function (n = 32) and the healthy controls . Conclusions: As a nonradioactive and noninvasive technique, CMR-TT has preferable feasibility and repeatability in quantitatively evaluating LV and RV strain parameters in PAH patients and can be used to effectively detect early biventricular myocardial damage in patients with PAH.To evaluate both left and right ventricular (LV and RV) function in patients with pulmonary arterial hypertension (PAH) using cardiac magnetic resonance tissue-tracking (CMR-TT) technology and explore its clinical value. Methods: A total of 79 participants  underwent cardiac magnetic resonance imaging (CMRI) with a short-axis balanced steady-state free precession (SSFP) sequence. The biventricular cardiac function parameters and strain parameters were obtained by postprocessing with CVI42 software. A comparative analysis was performed between the LV and RV strain parameters in all PAH patients and in PAH patients with reduced or preserved cardiac function. Results: The results showed preferable repeatability of CMR-TT in analyzing the global radial strain (GRS), circumferential strain (GCS), and longitudinal strain (GLS) of the left and right ventricles in the PAH group. The GRS, GCS, and GLS of the left and right ventricles except for LV GRS (LVGRS) of PAH patients were significantly lower than those of healthy controls ( Pulmonary arterial hypertension (PAH) is defined by a mean pulmonary artery pressure (mPAP) ≥ 25 mmHg at rest associated with pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, leading to right ventricular (RV) dysfunction and a rising afterload ,4. It haThe gold standard for diagnosing PAH is right heart catheterization (RHC) , which cEchocardiography and cardiac magnetic resonance imaging (CMRI) are common noninvasive methods for cardiac examination . CMRI haAt present, studies on ventricular strain in patients with PAH using CMRI have mostly focused on a single ventricle (particularly the right ventricle), while fewer studies have focused on biventricular myocardial strain analysis. The purpose of this study was to retrospectively analyze the correlation between the LV and RV strain, as well as the ventricular strain changes associated with cardiac function preservation among PAH patients.We retrospectively analyzed 47 patients diagnosed with PAH  Group 1) who underwent CMRI between February 2017 and March 2020. The inclusion criteria were those established according to the 2015 ESC/ERS guidelines . All pat2, matrix = 256 × 192, TR = 51.45 ms, TE = 1.51 ms; short-axis planes: 10 or 8 mm thickness, 0 mm gap, matrix = 216 × 256)  and a 3.0-T MR system  with a 32-channel phased-array surface coil and MR-compatible ECG and respiratory gating. Multiphase cine imaging was performed using a standard steady-state free precession (SSFP) pulse sequence in the LV two-chamber and four-chamber long-axis views and in the biventricular short-axis views with breath holding (field of view (FOV) = 340 × 360 mm6 × 256) .The acquired MRI data were processed using CVI42  by 2 experienced radiologists with more than 3 years of CMRI experience. The endometrium and epicardium of the left and right ventricles were semiautomatically delineated on the short axis of the ventricles at the end of diastole and end of systole, and the parameters of the cardiac function of both ventricles were obtained after making appropriate adjustments. The cardiac functional parameters included the end-diastolic volume (EDV), end-systolic volume (ESV), and EF.Biventricular myocardial strain parameters were measured using the CVI42 TT technique. The investigators selected the diastolic phase of the left ventricle, semiautomatically outlined the endocardium of both ventricles, marked the septum in the short-axis view of both ventricles, marked the valve plane and apical position in the standard four-chamber view and the two-chamber view of the left ventricle, and then automatically generated the 2D strain parameters and strain curves of both ventricles, as shown in t tests or nonparametric rank-sum tests were selected for comparisons between the two groups. We used one-way ANOVA for comparisons among PAH patients with a reduced EF, PAH patients with a preserved EF, and healthy controls. The relationship between LV and RV strain parameters in the PAH group was assessed using Pearson’s correlation analysis. p < 0.05 was considered to indicate a statistically significant difference.SPSS version 22.0 software  was used to conduct the statistical analyses. Continuous data were expressed as the mean ± standard deviation (SD). The Shapiro–Wilk test was used to test the normality of the strain parameters, and two independent sample Twenty patients with PAH were randomly selected, and CMR-TT postprocessing was performed by two radiologists who were blinded to the information of the patients. Consistency was tested by Bland–Altman analysis, along with an interclass correlation coefficient (ICC) to calculate the 95% limits of mean deviation and consistency.Among the 47 patients in the PAH group, there were 9 males and 38 females. In the healthy control group, there were 20 males and 12 females. The age and cardiac function parameters in the two groups are shown in The global LV and RV strain were reproducible at the interobserver level. Bland–Altman Plots for global strain of both ventricles are shown in p < 0.001) (p = 0.027), but no significant difference in LVGRS was observed (p = 0.077)  . We furt= 0.077) .p = 0.02; r = 0.301, p = 0.04, respectively). The GLS of the left and right ventricles was not statistically correlated   .p < 0.05 for all). Compared to that of control subjects, RVGRS, RVGLS, the basal, mid-segment, and apical of RVGRS  of PAH patients with preserved RV function was significantly impaired , while that of PAH patients with reduced RV function showed no significant difference. There were no significant differences in the basal RVGCS (RVGCS-b) among the three groups (p = 0.996) (The RV strain parameters in the three groups are listed in = 0.996) .p < 0.01 for all). There was a significant difference in the LVGLS between the PAH patients with preserved LV function and the healthy controls  . All LV strain parameters in PAH patients with reduced LV function were significantly lower than those in both PAH patients with preserved LV function and in healthy controls ( < 0.01) .Our findings provide data supporting the role of quantitative tissue techniques in noncontrast methods for identifying and monitoring patients with PAH. The strain parameters of the PAH patients in this study were measured independently by two investigators for the same 20 randomly selected patients. The obtained GRS, GCS, and GLS of the left and right ventricles showed good correlations in the Bland–Altman analysis, along with an interclass correlation coefficient (ICC) indicating that the CMR-TT technique is feasible and reproducible for the evaluation of biventricular myocardial strain parameters in patients with PAH ,20.Currently, several studies on RV strain in patients with PAH can be found. de Siqueira et al.  found siStrain has been suggested as a potential metric for evaluating early or subclinical changes in LV function. It performs better than the LVEF in reflecting myocardial deformation and has already been incorporated into alternative measurements of therapeutic results ,23. Kallp = 0.02), and the close relation between RVESV index with LVGCS and LVGRS  provides evidence of systolic ventriculo-ventricular interaction in PAH. Another recent study performed by Kallianos et al. [2 = 0.27, p = 0.047). Our findings are consistent with those of several previous studies, in that LVGCS and LVGRS but not GLS are significantly correlated with RVGCS and RVGRS, respectively . It suggested that the relationship between biventricular strain parameters might be related to inter-ventricular dependence. A potential explanation could be that the reverse septal curvature and a more D-shaped LV in patients with PAH might affect circumferential more than longitudinal myocardial fiber shortening [The analysis of biventricular GLS performed by Lindholm et al.  in PH pas et al.  revealedortening , this thThe RVGRS, RVGCS, and RVGLS in PAH patients with preserved RV function were significantly different from those in the controls. This result is also consistent with the study reported by de Siqueira , in whicp = 0.634, age-corrected p = 0.150), while there was a significant difference in the GLS, which is similar to the results of our present study. In addition, Padervinskiene et al. [Most related studies have focused on RV function in PAH patients, and there have been no definitive studies on strain analysis in PAH patients with preserved LV function. In this study, only the GLS was significantly different between PAH patients with preserved LV function and the controls, while the LVGRS and LVGCS showed no significant difference between these two groups. Kallianos et al.  reportede et al.  analyzedThis was a single-center, retrospective analysis of patients with PAH who underwent clinical CMRI. The number of PAH patients who underwent clinical CMRI during the study was restricted. This study’s other limitation might be that there were differences in the sex ratio between the control and patient groups. Previous studies have shown sex differences in the LV and RV strain in healthy individuals ,31, thusAs a nonradioactive and noninvasive technique, CMR-TT has preferable feasibility and repeatability for quantitatively evaluating LV and RV strain parameters in PAH patients and can be used to effectively detect early biventricular myocardial damage in PAH patients.


Strenuous exercise has been associated with functional and structural cardiac changes due to local and systemic inflammatory responses, reflecting oxidative, metabolic, hormonal, and thermal stress, even in healthy individuals. We aimed to assess changes in myocardial structure and function using cardiovascular magnetic resonance (CMR) imaging in master triathletes early after a full-distance Ironman Triathlon race.Ten master triathletes (age 45 ± 8 years) underwent CMR within 3 h after a full-distance Ironman Triathlon race  completed with a mean time of 12 ± 1 h. All the triathletes had a 30-day follow-up CMR. Cine balanced steady-state free precession, T2-short tau inversion recovery (STIR), tagging, and late gadolinium enhancement (LGE) imaging sequences were performed on a 1.5-T MR scanner. Myocardial edema was defined as a region with increased T2 signal intensity (SI) of at least two SDs above the mean of the normal myocardium. The extent of myocardial edema was expressed as the percentage of left ventricular (LV) mass. Analysis of LV strain and torsion by tissue tagging included the assessment of radial, longitudinal, and circumferential peak systolic strain, rotation, and twist.P = 0.004) and presented with a relative apical sparing distribution (P < 0.001) matched by reduction of radial peak systolic strain of basal segments (P = 0.003). Apical rotation and twist were significantly higher immediately after the competition compared with follow-up (P < 0.05).Compared with postrace, biventricular volumes, ejection fraction, and LV mass index remained unchanged at 30-day follow-up. Global T2 SI was significantly higher in the postrace CMR (postrace 10.5 ± 6% vs. follow-up 3.9 ± 3.8%, Strenuous exercise in master triathletes is associated with a reversible regional increase in myocardial edema and reduction of radial peak systolic strain, both presenting with a relative apical sparing pattern. Exercise training and moderate-to-high levels of physical activity have been shown to improve health outcomes and reduce cardiovascular morbidity and mortality –3. DespiIronman Triathlon  is a strenuous sports discipline, combining dynamic and static components and causing relevant cardiac adaptations –17. We hWe enrolled 10 healthy, amateur, Ironman triathletes , with a mean training time of 13 ± 9 years. The inclusion criteria for enrollment were: (i) experience with ultra-triathlon  races with at least two completed competitions; (ii) well-trained (>10 h of intense training per week); (iii) no known medical problems; (iv) no cardiovascular risk factors; and (v) no history of performance-enhancing drug use.The research study design complied with the Declaration of Helsinki and was approved by the local Ethics Committee . After receiving the description of the procedures and potential risks, all the subjects gave their written informed consent.Cardiovascular magnetic resonance was performed twice: (1) within 3 h following completion of the Ironman race (postrace) and (2) 30 days after the race (follow-up). The second CMR scan was performed in resting conditions, asking athletes not to exert physical activity for 2 days preceding the examination.Cardiovascular magnetic resonance examinations were performed using a 1.5-T Signa CVI scanner  with a cardiac phased-array 8-channel coil. Left ventricular (LV) and right ventricular (RV) volumes, mass, and function  were derived using steady-state free precession [Fast Imaging Employing Steady-State Acquisition (FIESTA)], pulse sequence cine images from the short axis , and para-axial views . The following acquisition parameters were applied: 30 phases, 10–25 views per segment depending on heart rate, the number of excitation (NEX) 1, the field of view (FOV) 40 cm, a matrix of 224 × 224, a 45° flip angle, repetition time/echo time (TR/TE) equal to 3.5/1.5 s, and a bandwidth of 125 kHz. T2-STIR images were acquired using triple inversion recovery T2-weighted pulse sequence in short-axis views and two long-axis views  using the following parameters: TR = 2 RR, TE 70 ms, FOV 40 cm, phase FOV 1, and matrix 256 × 256. LGE images were acquired 10 min after administering gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)  with a dosage of 0.2 mmol/kg. An inversion recovery T1-weighted gradient-echo sequence was used with the following parameters: FOV 40 mm, slice thickness 8 mm, no gap between each slice, TR 4.6 ms, TE 1.3 ms, flip angle 20°, matrix 224 × 224, reconstruction matrix 256 × 256, and an excitation number of 1. The appropriate inversion time was set to null for normal myocardium based on the Look-Locker scout sequence.Myocardial tagging images for calculation of LV systolic longitudinal, radial, and circumferential strain for basal, middle, and apical segments of the LV were acquired with an electrocardiography-gated, segmented K-space, fast gradient recalled echo pulse sequence with spatial modulation of magnetization to generate a grid tag pattern. Non-selective radiofrequency pulses separated by spatial modulation of magnetization encoding gradients allowed tag separation of 5 mm. Two sets of orthogonally intersecting tag lines were acquired in short-axis views at basal, mid, and apical levels. The number of views per phase was optimized based on the heart rate. The following parameters were used: field of view 40 cm, slice thickness 5 mm, no gap between each slice, repetition time 8 ms, echo time 4.3 ms, flip angle 12°, bandwidth 31 Hz, 30 phases, matrix 256 × 256, reconstruction matrix 256 × 256, and an excitation number of 1.Using dedicated software , the following functional parameters were obtained from the short-axis images: RV and LV end-diastolic volume indexed to body surface area, indexed RV and LV end-systolic volume, indexed LV mass, RV and LV ejection fraction (EF), and RV and LV stroke volumes. The indexed RV and LV volumes were compared with the respective age- and sex-specific reference values . Myocardt-test and ANOVA for immediate postrace vs. resting interslice comparison. One-way intraclass correlation coefficients (ICCs) were obtained to assess inter- and intraobserver variability. We considered a 2-sided p-value of <0.05 as statistically significant throughout. We ran all the tests with the R statistical software version 3.4.3.1Data were expressed as mean ± SD or percentages as appropriate. Differences in immediate postrace vs. resting parameters of the follow-up scans were explored using the paired The demographic and physical characteristics of triathletes are shown in P < 0.05), whereas LV ejection fraction remained unchanged.Postrace and resting structural and functional LV and RV parameters are shown in P < 0.05), whereas LV systolic basal radial strain significantly decreased postrace (P < 0.05)  –3.P = 0.004; P < 0.001) and a basal-to-apical gradient , and detailed data about the frequency, intensity, time, and type of training that led up to the competition. Finally, tissue characterization was limited to conventional T2-weighted STIR [with its intrinsic technical limitations , includiThe present study demonstrated significant early postrace changes in ventricular function and myocardial tissue composition and the full reversibility of these changes in a cohort of master Ironman triathletes. The results of this study add new insights regarding the acute cardiac response to strenuous and prolonged exercise on myocardial tissue component, function, and the reversible nature of these changes. In view of the variability of published results, larger multicenter studies are needed to confirm the presence, magnitude, and reversibility of myocardial functional and structural changes in order to help clarify the concept of cardiac fatigue and investigate the true prevalence of irreversible cardiac injury linked to intense and prolonged exercise.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study involved human participants and has been reviewed and approved by the local Ethics Committee  of Pisa, Italy.AP: full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. FR, GA, and AP: study concept and design. FR, GA, AP, CM, and SR: acquisition, analysis, or interpretation of data. FR, AP, and CD: drafting of the manuscript. FR: statistical analysis. GA: administrative, technical, or material support. SG and AP: study supervision. All authors critical revision of the manuscript for important intellectual content and approved the submitted version.


There have been several reports on the identification of the stage of transthyretin amyloid cardiomyopathy (ATTR-CM); however, a staging system for ATTR-CM has not yet been established. An 83-year-old woman was referred to our department about ten years ago. Recently, she was diagnosed with ATTR-CM. The electrocardiogram showed characteristic changes that take place over the duration of ATTR-CM progression. Among these, the precordial R amplitudes abruptly decreased before the development of increased ventricular thickness. This case suggested that the decrease in the precordial R wave amplitudes may represent a new diagnostic clue reflecting early myocardial damage due to ATTR-CM. Several therapeutic agents have been developed for the purpose of transthyretin amyloid cardiomyopathy (ATTR-CM) . As a reThe present case of ATTR-CM represented characteristic changes in the electrocardiogram (ECG) with the progression of ATTR-CM over a 10-year period.An 83-year-old woman undergoing treatment for hypertension and sleep apnea syndrome was referred to our department in 2014 for shortness of breath on exertion. The ECG results were within the normal limits. Echocardiography showed normal contractility, without an evident increase in ventricular thickness, and cardiac magnetic resonance (CMR) scans showed no significant stenosis in the coronary arteries.In 2016, her shortness of breath worsened. Echocardiography showed only grade II diastolic dysfunction. However, no other abnormalities were detected that could explain her symptoms. The blood pressure was controlled, and the patient was under observation.In 2020, she developed numbness in both hands, which suggested the presence of carpal tunnel syndrome (CTS). At that time, increased ventricular thickness, observed on echocardiography, was evident for the first time A,B. TechAccording to the detection of the early signs of ATTR-CM using ECG, her ECGs, which were taken every 1–2 years from 2007 onwards, were analyzed retrospectively. No abnormalities were evident on ECG until 2014. Then, the R waves of leads V1–3 abruptly decreased in 2016 D,E, whicIn contrast, there were no overt changes in the findings of the low potentials, PR duration, or QTc time before the detection of increased ventricular thickness. The increase in the QRS width became evident after 2020.Despite the initiation of tafamidis, recent ECG findings showed that the PR duration, QTc time, and QRS duration were all increased B.The ECG parameters were calculated by a visual assessment (R wave summation) and partly by computer-aided assessment . The LV thickness was measured using a long-axis view of a still image to detect the end-diastole with 2D tracing.In addition, we analyzed other cases in order to verify relationship between the summation of the amplitudes of the R waves in the V1–3 leads and increased ventricular thickness in ATTR-CM over time. We screened cases taken from our ATTR-CM cohort, which consisted of 32 cases with ATTRwt and 15 cases with a variant type of ATTR. From these, we extracted seven cases, for which a series of ECGs were recorded before the onset of increased ventricular thickness. Among the seven cases, three cases were excluded because two patients showed poor R progression after the first visit, and one patient had complete right bundle branch block. After excluding these cases, four cases (including the main case) remained, as described in ATTR-CM, which was previously considered as a rare condition, is increasingly recognized as a cause of heart failure in the elderly . There iIn addition, the natural history of cardiac dysfunction is not well understood in patients with ATTR. Technetium-labeled cardiac scintigraphy and CMR have proven to be useful for the diagnosis of ATTR-CM in patients with a high pre-test likelihood, but its usefulness is limited to a screening method, and the validity of frequent evaluation using these modalities to assess the grade of TTR deposition has not yet been demonstrated ,7,8. TheFor the effective monitoring of the progression of ATTR-CM, ECG might be a possible candidate for disease stage monitoring because of its simplicity. Typical ECG changes seen in ATTR include a low voltage, pseudo-infarct pattern, poor R wave progression (PRWP), atrioventricular block and atrial arrhythmias ,12.The definition of PRWP is an R wave amplitude of 3 mm or less in the precordial lead in V3, and an R wave amplitude in the lead in V2 that is equal to or smaller than the R wave amplitude in V3 . AlthougRegarding the findings of a low voltage, the prevalence was reported to be dependent on the definition. They also reported that low voltages based on limb leads lower than 0.5 mV and precordial leads lower than 1.0 mV were infrequent in ATTR-CM patients (6–38%). Low voltages based on the Sokolow criteria lower than 1.5 mV were more common (53–58%). Other ECG findings related to ATTR-CM include the increase in the PR interval, QRS width, PR interval, and QTc, which are, however, less frequent than PRWP . Light-cAccording to the change in the ECGs observed in this case over time, the changes in the PR interval and QTc time were too slight to notice. The increase in the QRS was observed with the appearance of obvious cardiac hypertrophy. Only PRWP was identified as an abnormal change prior to the detection of cardiac hypertrophy, suggesting that PRWP could detect the earliest myocardial change in the TTR deposition. Indeed, we could verify the usefulness of the summation of the amplitudes of the R waves in the V1–3 leads based on the detection of the progression of ATTR-CM in the other cases (2 cases of ATTRwt and 2 cases of variant-type of ATTR). While there are few reports that explain the relationship between the ECG changes and the stage of ATTR amyloidosis, it has been proposed that the ECG changes in Fabry disease reflect the stage of the disease to some extent. In Fabry disease, short P waves and specific T wave patterns are confirmed before the detection of increased ventricular thickness on echocardiography, and the ECG reveals characteristic changes as the disease progresses . As in tThe mechanism for the appearance of a specific ECG pattern before the development of increased ventricular thickness may be related to the multistep process of amyloid deposition. A recent report suggested that organ damage occurs at the stage of nonfibrillar TTR before amyloid deposition was observed in the organ . In ATTROur case suggests that the decrease in the R wave amplitudes of the V1–3 leads may appear earlier than the echocardiographic findings of cardiac hypertrophy. Among the ECG changes characteristic of ATTR-CM, the summation of the amplitudes of the V1–3 R waves is the most obvious change in the early stage of ATTR-CM. The monitoring of ECG changes is easy and cost-effective and is likely to be useful for the early detection of myocardial damage in ATTR patients, especially in patients with asymptomatic TTR variants or in patients with TTR detected in other organs. Further research is needed in order to investigate the relationships between the various findings of different modalities.There is one limitation of this case series. The parameters of the ECG and increased ventricular thickness on echocardiography are generally subject to intra- and inter-observer viabilities. In order to solve this problem to the greatest extent possible, the parameters were plotted at numerous time points, which might have lessened the effects of variations in the individual parameters measured .In conclusion, the decrease in the R wave amplitudes of the V1–3 leads may be a new diagnostic clue reflecting early myocardial damage due to ATTR-CM, and this finding could enable the concise follow-up of gradual changes in the TTR deposition, leading to a more appropriate therapeutic strategy.


Echinococcus multilocularis infects humans as a false intermediate host, primarily with intrahepatic manifestation. Incorrect diagnostic interpretation of these liver tumors, especially the hemangioma-like pattern, can lead to progressive disease. The aim of the study was to investigate the differentiation of typical hemangioma and a hemangioma-like pattern of E. multilocularis using contrast-enhanced ultrasound (CEUS).n = 14) and patients with alveolar echinococcosis (AE) and hemangioma-like pattern (n = 7). Inclusion criteria were the detection of a liver lesion according to a hemangioma-like pattern on E. multilocularis Ulm classification—ultrasound (EMUC-US) and “confirmed” or “probable” AE according to WHO case definition. The comparison group had hepatic hemangioma with typical B-scan sonographic morphology. All participants underwent conventional and contrast-enhanced ultrasonography.This prospective clinical pilot study comprised patients with hemangioma (p < 0.0001) and iris diaphragm phenomenon could only be visualized in the patients with hemangioma (p < 0.0001). Furthermore, the patients with hemangioma exhibited hyperenhancement in the late phase (p = 0.0003). In contrast, the patients exhibited typical early arterial rim enhancement (p < 0.0001) and, in the portal venous and late phase, complete or incomplete non-enhancement .The patient group comprised five men (71.4%) and two women (28.6%) with a mean average age of 64.1 ± 11.2 years. The patient group with hemangioma comprised nine female subjects (64.3%) and five male subjects (35.7%) with a mean average age of 56.1 ± 12.0 years. Early arterial bulbous ring enhancement (The behavior of hemangioma-like AE lesions and typical liver hemangiomas is significantly different on CEUS. AE should be considered as a possible differential diagnosis, especially in high-endemic areas. Echinococcus multilocularis, for which humans may act as a false intermediate host. The worm eggs are ingested accidentally, penetrate the small intestinal wall and travel to organs via the blood or lymphatic vessels. In a majority of cases, AE primarily affects the liver and forms infiltrative alveolar space-occupying lesions, similar to a malignant tumor FDG uptake in 18FDG positron emission tomography (PET) suggests that discontinuation of mebendazole therapy is feasible  homogeneous hemangiomas and 14.3% [2/14] inhomogeneous hemangiomas (p = 0.00031). All hemangiomas presented without perfusion using standard Doppler techniques  of the AE lesions had a polycyclic shape, whereas all 14 (100.0%) hemangiomas had round-oval presentation      Fig. a. In one01) Fig. a. All AE04) Fig. a. No sig0) Table .Fig. 4a p < 0.0001)   and 2 with iso-enhancement (p = 0.5333) in the late phase  Fig. b. In the01) Fig. b. Of theThis is the first prospective clinical study to evaluate AE patients with a hemangioma-like pattern classified by EMUC-US in contrast-enhanced sonography and compare them to patients with typical hepatic hemangioma. The results of this study support the hypothesis that typical hemangiomas and AE space-occupying hemangioma-like lesions differ significantly on CEUS.Multiple prior studies also observed early arterial rim enhancement and black hole sign in fox tapeworm lesions , 17–21. [18F]FDG uptake on PET-CT and demonstrated increased PET activity for type I–III microcysts [The hemangioma-like pattern of AE and its difficult differential diagnosis from atypical hemangioma on B-scan ultrasonography was first described by Bresson-Hadni et al. in 2006 . Consistcrocysts . Given tcrocysts . Our stucrocysts –33.The small number of included patients with AE with a hemangioma-like pattern must be considered a limitation. Furthermore, the patients with hemangioma consisted of nine women and only five men. However, a possible different contrast behavior of hemangiomas between women and men has not been described in the literature so far. Due to the rarity of the disease in Germany, further multicenter studies are necessary to confirm the results.Our work shows that hemangioma-like AE lesions classified by EMUC-US differ from typical liver hemangiomas on CEUS. In the presence of early arterial rim enhancement and black hole sign, the diagnosis of AE should be considered. When a hemangioma-like liver lesion is first diagnosed, CEUS of the liver should be performed in high-endemic areas to rule out hepatic AE.


PA diameter was associated with LV end-diastolic volume . Interestingly, the PA/Ao ratio was only associated with RV end-diastolic and end-systolic volume . Furthermore, we found different relationships between men and women. Ao and PA diameter were associated with LV and RV volumetric parameters in subjects free of cardiovascular diseases suggesting that ventricular volumetric performance directly relates to vascular diameter properties.To investigate the association between Aorta (Ao), pulmonary artery (PA) diameters and the PA/Ao ratio with right (RV) and left ventricle (LV) volumetric properties in subjects free of cardiovascular diseases. In the KORA-MRI study, 339 subjects  underwent whole-body 3T-MRI. Ao and PA were measured on DIXON sequences. Cvi42 quantified cardiac functional parameters from a SSFP sequence. The relationship between ascending (AAo), and descending aorta (DAo), as well as PA diameters, and RV and LV function were assessed using linear regression models adjusted for age, sex, and cardiovascular risk factors. AAo and DAo diameter were associated with LV end-diastolic volume (β = 4.52,  Left ventricular (LV) performance is the primary determinant of cardiac function, which may be influenced by arterial properties ,2. UnderThe KORA-MRI study enrolled participants aged 25 to 74 years old from the Augsburg region of Germany . Between2, slice thickness (ST) 3 mm, field of view (FOV) 297 × 360 mm, matrix 320 × 195, repetition time/echo time (TR/TE) 4.1/1.23; 2.46; 3.69; 4.92; 6.15; 7.38, flip angle (FA) 9°. For analysis of the cardiac parameters, the cine-steady-state free precession sequence was obtained in a short-axis perspective with 10 layers and 25 phases. A FOV of 297 mm × 360 mm, a matrix of 240 × 160, a TR of 29.97 ms, a TE of 1.46 ms, and a FA of 62° were all included in the 8 mm slice thickness.The whole-body MRI scans were performed using a 3-Tesla MRI system   with an The outer diameters were measured at two predefined aortic segments: AAo and descending aorta (DAo) at the level of the right pulmonary artery (RPA) . DiameteCine steady-state free precession (cine-SSFP) sequences were performed for imaging of heart function, morphology, and cardiac morphology disorders. The LV and RV function was assessed using Circle Cardiovascular Imaging Inc.’s cvi42 software (version 4.1.5 190), Calgary, Alberta, Canada). The detection of LV contours and calculation of LV volumes were done automatically, then manually corrected, if necessary , and the0, CalgarPhysical examination, interview, and blood samples were used to collect information on risk factors. Body mass index (BMI) and body surface area (BSA) were determined using height and weight, and smoking status, as well as antihypertensive and lipid-lowering medicine (statin usage), were evaluated using a questionnaire. Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg, or current antihypertensive therapy were all considered hypertension. Prediabetes  glucose concentration between 140 and 200 mg/dL; and/or impaired fasting glucose concentration, as defined by fasting glucose levels between 110 and 125 mg/dL and an average 2-h serum glucose concentration), and diabetes (2-h serum glucose concentration as determined by OGTT that was >200 mg/dL and/or a fasting glucose concentration between 110 and 125 mg/dL) were defined according to the WHO criteria [For continuous and categorical variables, the distribution of demographic characteristics was reported using mean and standard deviation (SD), median (interquartile ranges (IQRs)), or percentages, respectively. We employed a multi-step approach, first focusing on the relationship between the diameter of AAo and ADo, and LV and RV functional characteristics using linear regression models. We adjusted for sex and age in model 1. Smoking, BMI, systolic blood pressure, diastolic blood pressure, and diabetes mellitus were additionally adjusted in Model 2. Model 3 was also adjusted for cholesterol, triglycerides, hypertension medication, and lipid-lowering medication. Second, using the above-mentioned linear regression models, we investigated the relationship between MPA, RPA as well as LPA, the ratio of MPA/Ao, and RV and LV function characteristics. Third, using the same models as in linear regression analysis, stratified analyses for sex were carried out. Stata was used to conduct all analyses .There were significant associations between ascending AAo and ADo diameters and LV and RV functional parameters. AAo and ADo diameter were positively associated with LV end-diastolic volume, end-systolic volume, stroke volume, peak ejection rate, and mass . In contThe diameters of the pulmonary artery system were significantly related to LV and RV functional characteristics. The diameter of the MPA was positively associated with LV end-diastolic volume, stroke volume, peak ejection rate, early diastolic rate, late diastolic rate, mass, as well as with RV end-diastolic volume, end-systolic volume, and stroke volume, but not with LV or RV ejection fraction . The diaIn females , the diaIn females , the diaIn males , the diaIn this sample with subjects free of cardiovascular diseases, our results indicate that larger AAo and ADo diameters were positively associated with LV volumetric parameters, while the ADo diameter was associated with RV volumes. Furthermore, the MPA was positively associated with LV and RV volumetric parameters, while the ratio of MPA/Ao was related to RV end-diastolic and end-systolic volumes.To date, our study is the first to evaluate the relationship between the aorta and pulmonary artery segments and cardiac volumes in a healthy cohort without established cardiovascular disease. Previously, the data from the CARDIA study, based on echocardiography assessments with a follow-up of 20 years, showed that increased aortic root seize was associated with increased LV mass and concentric LV remodeling in subjects from early adulthood to middle age, confirming a direct link between large artery diameter and cardiac performance . Our stuSeveral risk factors influence the vascular system, affecting various conditions . The preThe link between aorta diameter and LV volumes has been assessed in an athletes’ population, and the study reported a significant relationship between ascending aorta dilatation and LV performance . Our finThe diameter of MPA, and its relation to the diameter of AAo has been used to identify patients at risk  and was The major strength of the study incorporates the implementation of advanced 3T-whole-body MRI technology with a detailed protocol. Whole-body MRI allows simultaneous assessment of the heart, great vessels, and lungs at a single time point for reliable real-time assessment of cardiopulmonary function. In addition, automated algorithms for MR image analysis have been used to quantify cardiac functional volume. With the increasing establishment of machine learning, whole-body MRI may become increasingly attractive as a one-stop-shop model, especially with regard to personalized medicine. Furthermore, multi-level adjustment was applied to confirm the results. The study recruited healthy individuals free of cardiovascular diseases from a population-based cohort. Nonetheless, there are limitations necessary to mention. First, although the MRI protocol included atria, the atria size or function was not used in adjustment. Second, cross-sectional design study limits to draw causal inferences, and generated hypotheses require further confirmation in other designs and populations. Third, the study represents a relatively small number of participants from the population-based cohort. Fourth, the generalizability of findings may be limited to other populations or geographical regions.In conclusion, larger aorta and pulmonary artery diameters were positively associated with LV and RV volumetric parameters in subjects free of cardiovascular diseases suggesting that ventricular volumetric performance directly relates to vascular diameter properties. Further studies with longitudinal designs are needed to confirm our findings.


CMR score had potential to screen for early cardiac involvement in IIM patients, compared to MDAAT.Idiopathic inflammatory myopathies (IIM) is a group of heterogeneous autoimmune systemic diseases, which not only involve skeletal muscle but also myocardium. Cardiac involvement in IIM, which eventually develops into heart failure, is difficult to identify by conventional examinations at early stage. The aim of this study was to investigate if multi-parametric cardiac magnetic resonance (CMR) imaging can screen for early cardiac involvement in IIM, compared with clinical score . Forty-nine patients of IIM, and 25 healthy control subjects with comparable age-range and sex-ratio were enrolled in this study. All subjects underwent CMR examination, and multi-slice short-axis and 4-chamber cine MRI were acquired to evaluate biventricular global circumferential strain (GCS) and global longitudinal strain (GLS). Native T1 and T2 mapping were performed, and post-contrast T1 mapping and LGE were acquired after administration of contrast. A CMR score was developed from native T1 mean and T2 mean for the identification of cardiac involvement in the IIM cohort. Using contingency tables MDAAT and CMR were compared and statistically analyzed using McNemar test. McNemar’s test revealed no significant difference between CMR score and MDAAT ( Cardiac involvement in IIM, occurring in around 75% of IIM patients, is an important extramuscular manifestation and a major cause of mortality in PM and DM as it eventually develops into heart failure4. However, about 70% of patients only have subclinical involvement6, which fails to be identified at an early stage due to lack of sensitive screening tools. Early detection of cardiac involvement in IIM is essential for timely treatment to prevent further adverse remodelling and cardiac mortality in this patient group.Idiopathic inflammatory myopathies (IIM) is a group of heterogeneous autoimmune systemic diseases characterized by skeletal muscle inflammation, including polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) and inclusion body myositis (IBM)10. This method needs various time consuming and costly clinical examinations, including cardiac-specific serological markers, electrocardiography and echocardiography, but lacks the sensitivity to screen for subclinical cardiac involvement in IIM. Once symptoms appear in IIM patients, most of them has morphological or functional changes, which progress rapidly and even lead to heart failure. To improve the sensitivity of cardiac involvement in IIM patients, advanced diagnostic tools are of significant clinical interest.Endomyocardial biopsy is considered as the golden standard to diagnose cardiac involvement in IIM, but it is limited in clinical practice due to its invasiveness and risk of complication. In clinical practice, cardiac involvement in IIM is usually diagnosed by the Myositis Disease Activity Assessment Tool (MDAAT)11. Late gadolinium enhancement (LGE) can detect focal fibrosis in the myocardium and is a highly specific indicator of cardiac injury in IIM. However, it is also lacking in sensitivity, as IIM patients without focal enhancement may still have myocardial involvement in the form of diffuse fibrosis4, which is not detectable by LGE MRI. In previous studies, it was reported that LGE only presents regions of focal hyper-enhancement in 19–35% of patients with IIM13. In addition, LGE requires administration of Gadolinium-based contrast agents (GBCA), which limits its use in IIM patients with GBCA allergy and renal dysfunction.Cardiac magnetic resonance imaging (CMR) is an advanced tool for evaluation of cardiac morphology, function, and tissue characteristics14. Previous studies have shown that up to 90% of LGE-negative IIM patients actually had elevated T1 and T2 values compared with normal15, which can reflect disease progression. Furthermore, it has also been reported that myocardial strain assessed by CMR or echocardiography can reveal subtle myocardial remodelling in different patient cohorts with preserved left ventricular ejection fraction (LVEF)17, thereby more sensitive than traditional imaging markers for detecting subclinical myocardial involvement.With the recent MR T1 and T2 mapping techniques, diffuse fibrosis and edema can be quantitatively assessedWe hypothesize that multiple relevant CMR parameters, including the tissue and mechanical properties of the myocardium as quantified by T1, T2, and strain, may improve the screening performance of cardiac involvement detection in IIM patients. The purpose of this study was therefore to develop a multi-parametric CMR score for the detection of subclinical myocardial involvement in IIM patients.15.This study was approved by the local Institutional Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-C20121221), and written informed consent was obtained from all participating subjects. It complies with the ethical principles of the Declaration of Helsinki. A cohort of 57 consecutive patients with confirmed idiopathic inflammatory myopathy (IIM) screening for myocardial involvement were enrolled in this study from October 2015 to October 2020. All patients underwent skeletal muscle biopsy, laboratory tests of blood, muscle and myocardium enzyme, and myositis—specific as well as myositis-associate autoantibodies, electromyography, electrocardiography, echocardiography, and CMR. Some IIM patients were included in a previous study of our team published before19 and the recommended diagnostics by the International Myositis Classification Criteria Project (IMCCP)2. Patients with immune-mediated necrotizing myopathy (IMNM) were diagnosed according to the ENMC criteria8. Cardiac involvement in IIM was diagnosed using the Myositis Disease Activity Assessment Tool (MDAAT)-cardiac domain20. Assessment of pericarditis, myocarditis, arrhythmia and sinus tachycardia were based on clinical manifestation, hs cTnI, electrocardiography, echocardiography, and conventional CMR. Pericarditis was diagnosed according to the 2015 ESC Guidelines for the diagnosis and management of pericardial diseases21, in patients who satisfied at least 2 of 4 diagnostic criteria. Patients who met clinical diagnostic criteria22 proposed by the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases were defined as clinically suspected myocarditis. Arrhythmia  and sinus tachycardia (i.e. sinus rhythm with heart rate more than 100 beats per minute) were diagnosed based on electrocardiography.Patients with PM and DM were diagnosed according to the Bohdan and Peter criteria9. Disease activity of cardiac involvement was evaluated by visual analogue scale (0–10 cm), with 0 representing no activity, 5 representing moderate activity, and 10 representing severe activity23. Exclusion criteria included: (1) history of coronary artery disease, myocarditis, cardiomyopathy, and valvular heart disease, (2) MR contraindication, (3) history of allergy to Gadolinium-based contrast agent, and (4) pregnancy. A flowchart of patient enrolment is shown in Fig. Cardiac involvement was defined as cardiac visual analogue scales (VAS) on the MDAAT > 0, which was based on diagnosis and disease activitiy assessment of pericarditis, myocarditis, arrhythmia and sinus tachycardia scale 0–0 cm, witAll subjects underwent CMR imaging on a 3T MR scanner  using an 18-channel cardiac coil. All images were acquired with retrospective ECG gating during breath-hold. The CMR protocol consisted of 4-chamber steady-state-free-precession (SSFP) cine and a stack of short-axis SSFP cine, short-axis native/post-contrast T1 mapping, T2 mapping and late gadolinium enhancement (LGE) imaging. Typical parameters of SSFP were: echo time (TE) = 1.39 ms, repetition time (TR) = 2.50 ms, field of view (FOV) = 320–360 mm, matrix = 192 × 146, flip angle (FA) = 47°, slice thickness = 8 mm, slice gap = 2 mm. The T1/T2 mapping and LGE sequences had the same imaging plane as the short-axis cine.Native T1 mapping was acquired using an ECG-gated single-shot modified Look-Locker inversion recovery (MOLLI) sequence. The scan protocol was 5(3)3, with TE = 1.2 ms, TR = 322.48 ms, FOV = 320–360 mm, matrix = 192 × 144, FA = 35°, slice thickness = 8 mm, 72 segments, minimum TI = 100 ms, TI increment = 80 ms, GRAPPA acceleration factor = 2, imaging window = 136 ms. The T2 mapping technique involved a T2 prepared pulse sequence to produce single-shot T2 prepared SSFP images (T2p-SSFP), with different T2 preparation times . The images were generated with three heart-beat recovery durations for each T2 preparation . LGE imaging was performed 10–15 min after intravenous administration of gadobenate dimeglumine  using a phase-sensitive inversion-recovery (PSIR) sequence . Post-contrast T1 mapping was performed after 15 min following the administration of gadolinium using the MOLLI scan protocol of 4(1)3(1)2. All native T1, T2 mapping and post-contrast T1 mapping were acquired on the whole LV, which were same to short-axis SSFP cine. Haematocrit (HCT) was measured within 3 days of CMR scanning for extracellular volume (ECV) calculation.All CMR images were analysed by two experienced radiologists (L.H. and P.Z.) using the MASS research software . LV/RV volumetric and functional parameters, including end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and mass were evaluated by manually drawing the endocardial and epicardial contours at the end-diastolic and end-systolic phases of the short-axis cine images. All volumes and masses were normalized by the body surface area (BSA).For both T1 and T2 mapping, a built-in algorithm was applied for motion correction by the MR scanner before parametric fitting. Examples of segmentation and histograms are shown in Fig. Focal scar within the myocardium was categorized as present or absent on the LGE images by two observers in consensus after reading all PSIR images independently. A senior observer  adjudicated any discrepancies between two observers.Automated deformable image registration was used to calculate LV/RV longitudinal strain from the manually traced endocardial contours at the end-diastolic phase of the 4-chamber cine images and biventricular circumferential strain was derived from the short-axis cine acquisition in all slices. Global strain values were averaged over all slices.2 test for categorical variables. A CMR score was developed to screen for cardiac involvement in IIM, which was defined as pathological if T1 mean and/or T2 mean is above the 95% quantile in the healthy volunteers. If either of the patient's T1 and T2 values was above the 95% percentile, the score was defined as 1, and if both T1 and T2 value were above the 95% percentile the score was defined as 2, while neither of T1 and T2 value were above the 95% percentile the score was defined as 0. The CMR score > 1 was defined as "abnormal T1 or T2 value", i.e. cardiac involvement. The comparison between MDAAT and CMR score with their dichotomous answers were used to construct contingency tables and statistically evaluated using McNemar test. For McNemar’s test, binary ordinal cardiac involvement data was generated for each methods and transferred to a contingency table. Receiver operating characteristic (ROC) curve analysis was used to assess the screening sensitivity of T1/T2 mapping parameters to detect cardiac involvement in IIM. A P value lower than 0.05 was considered statistically significant.Statistical analysis was performed using SPSS . Categorical variables were expressed as counts (percentage), and continuous variable as mean ± SD or median (interquartile range). Normality of distribution was tested using the Shapiro–Wilk test. We differentiated three categories of subjects: IIM patients with myocardial involvement (n = 37), IIM patients without myocardial involvement (n = 12), and healthy controls (n = 25). Comparisons among IIM patients with/without myocardial involvements and controls were performed by the analysis of variance (ANOVA) for normally distributed or Kruskal–Wallis test for non-normally distributed variables. Comparison between any of the two classes were performed by t-test  or Mann–Whitney U test  in case of continuous variables, or χ+) using the clinical criteria (MDAAT) as detailed in “-). Twenty-five healthy volunteers with similar age-range  and similar sex-ratio , without cardiovascular disease, metabolic diseases and systemic inflammation, were enrolled as the control group.Forty-nine IIM patients were finally enrolled in this study, including 37 patients with myocardial involvement . Heart rate of IIM-C+ was higher than controls . Blood hs cTnI in IIM-C+ patients’ group was higher than in IIM-C- patients . Fourteen of 37 (38%) IIM-C+ patients had elevated hs cTnI level . The other serological biomarkers  showed no significant difference between IIM-C+ and IIM-C- groups  among the three groups. Compared to the controls, LV global longitudinal strain (GLS) (adjusted p = 0.001), RV GCS and RV GLS of IIM-C+ patients were reduced significantly . However, LV GLS, RV GCS and RV GLS did not show significant difference between the IIM-C- and IIM-C+ groups .Compared to the healthy control group, all LV and RV volumetric and functional parameters showed no significant difference in IIM-C+ and IIM-C− groups Table . All LGE+ than in IIM-C- .Mean of native T1/T2 mapping and extracellular volume (ECV) are reported in Table - group . Combined T1 mean and T2 mean, the AUC of ROC curve was 0.788  with sensitivity of 81.1% , which may screen for cardiac involvement in IIM patients, compared to MDAAT. The CMR score only requires native T1 and T2 parameters, without the need for contrast agent administration and is therefore applicable in patients with contraindications for GBCA. Further study should be performed to validate our CMR score accuracy, which potentially facilitates early treatment to prevent cardiac mortality in IIM patient group.


Normal pulmonary artery (PA) diameter remains blurred and the definitions of PA aneurysm are heterogenous. We aimed to assess PA diameters, identify a threshold for normal diameters, define PA aneurysms, possible predictors of PA size and evaluate the correlation with mid-ascending aortic diameters.Between April 2018 and August 2019, 497 consecutive patients who underwent whole-body computed tomographic angiography were reviewed. Clinical and imaging data were collected from our institutional database. Precise three-dimensional centreline measurements were taken. Linear regression analysis was performed to detect parameters associated with PA diameter. A two-stage model was created to identify potential predictors and the resulting statistically significant interactions were tested. Data were grouped and PA, standard deviation, and upper normal limits were calculated.P = 0.032]. The mean PA length, left PA and right PA diameters were similar between male and female patients. We found a significant correlation  between the PAs and mid-ascending aortic diameters. Body surface area  was the only significant influencing variable for PA diameter.Among 497 patients with an average age of 51.4 (20.2) , the mean PA diameter measured 32.0 (4.6) mm . Pulmonary artery aneurysms (PAA) are rare, and their incidence is low . PAA is The aim of this study was to assess PA diameters, identify a threshold for normal diameters and define PAA. We also aimed to identify possible risk factors and influencing predictors of PA size and evaluate any correlation with mid-ascending aortic diameters in high-quality computed tomography (CT) scans.IRB approval was obtained on 27 February 2020 by the institutional review board of the University of Freiburg (# 71/20). Informed consent was waived due to our analysis’ retrospective nature. There was no patient and public involvement regarding analysis,Seven hundred and eighteen consecutive patients underwent whole-body CT for suspected trauma injuries at the Emergency Department of the University Hospital Freiburg, Germany, between April 2018 and August 2019.n = 15), age <18 years (n = 26), pulmonary embolism (n = 1), pulmonary fibrosis (n = 4), tension pneumothorax (n = 1), acute aortic syndrome (n = 6), poor quality scans (n = 5), extra-corporal life support (n = 3) and previous aortic surgery (n = 1) to reduce the bias of contributing diseases on PA diameter. The clinical database was reviewed for demographic data and cardiovascular risk factors, which revealed missing data on an additional 159 patients. Accordingly, our final cohort comprises 497 patients for careful analysis. Patient selection is shown in Clinical and imaging data were collected retrospectively from our institutional database. Patients were excluded for the following reasons: non-contrast-enhanced scans  following the split bolus technique application protocol for contrast agents (region of interest in the ascending aorta).2) of the pulmonary trunk and right and left PA were calculated subsequently. The length of the pulmonary trunk was measured from the pulmonary valve to the PA bifurcation. We analysed the ascending aorta’s length from the aortic valve to brachiocephalic trunk and its largest diameter, as well as the surface within that segment. Detailed stepwise measurements are shown in Fig. CT images were transferred to imaging software  for precise three-dimensional measurements using the software’s CPR tool. The centreline of the pulmonar(Color online) y trunk and PA was defined automatically and adjusted manually if necessary. Diameter and surface area  for maximum PA length, and the diameters of left PA, right PA and PA. We then summarized the PA characteristics after stratifying the patients by age and BMI. Lastly, we created an exploratory model to identify possible predictors for pulmonary trunk diameter from a two-stage, stepwise, backward selection process, with significance levels of 0.10. At stage 1, we started with a full linear regression model containing all potential influencing factors, including age , sex, body surface area (BSA) (m2 as continuous variable), BMI (kg/m2), smoking history, diabetes mellitus, dyslipidaemia, hypertension and coronary artery disease. Subsequently, at stage 2, we began selecting by specifying a full model with all main effectors, i.e. remaining variables from the stage 1 selection, as well as all possible pairwise interaction terms between the main effectors. The sum of cardiovascular risk factors was included as continuous variable. Robust variance estimators were used in all regression steps , respectively. We refrained to test PA diameter for normality as normality can be assumed for large thoracic vessels. To assess the difference between male and female patients, we performed Pearson’s Chi-squared tests on binary variables and the Student’s on steps . All ana2) and mean BMI 25.8 (4.8) kg/m2. Hypertension was the most common cardiovascular risk factor .Our final study population comprises 497 patients . The mean BSA was 2.0  mm and 83.6 (15) mm, respectively. We noted a significant difference in diameter and length in men and women. The PA diameter was 32.0 (4.6) mm [female: 31.2 (4.7) mm vs male: 32.2 (4.5) mm; The stage I models of potential predicators revealed that age, BSA and smoking were significant predictors of mean pulmonary trunk diameter. The stage I model is shown in The corresponding upper limits of the respective diameters were 41 mm (PA), 34 mm (right PA), 33 mm (left PA) and 78 mm (PA length). Detailed PA diameter stratifications by age and BSA are shown in Table Using these values, regular mean PA diameter can be calculated according to the patient’s individual risk profile. The formula for predicting the mean PA diameter in patients younger than 45 years of age is 4.31 × BSA + 22.56, in patients aged 45–54 years is 4.7 × BSA + 23.37, 55–64 years is 5.71 × BSA + 20.43 and older than 65 years of age is 4.6 × BSA + 24.27, which means that one only has to calculate the BSA according to the patient’s weight and height and insert this value in the equation of the respective age category.www.pa-diameter.com).We have created an online calculator to calculate the normal diameter of the PA diameter based on age, height, weight, sum of cardiovascular risk factors and smoking history  between PA and the mid-ascending aortic diameter.Figure This study’s 3 most essential findings can be summarized as: (i) normal mean PA diameter in a representative patient cohort (primarily non-cardiovascular patients) is 32.0 ± 4.6 mm; (ii) BSA is the only influencing variable of PA diameter; and (iii) measured normal diameters and the corresponding upper limits of normal, as well as the previous definition of arterial aneurysms  revealed that our threshold’s definition for PAA should not be <45 mm.et al. [ectasia may be appropriate.Few studies have investigated the issue of PAA or discussed what constitutes normal diameters of the main, right and left PAs and their correlation with the ascending aorta’s diameter. The current definitions mainly rely on postmortem data from Deterling and Clagett in 109 571 cadavers published 1947  and the et al. . What iset al.  and >1.5Previous studies have identified the thoracic aorta’s normal diameter and predictors of an increasing aortic diameter  . The facWhile this study helps considerably to specifically define a PAA, 2 questions remain regarding a possible diameter threshold for interventions and how a PAA should be treated. There seems to be general consensus in the literature for smaller PAAs to be medically managed conservatively, since PAA-associated complications such as dissection, rupture or local displacement of surrounding structures occur seldom and are more likely to occur in PAAs of larger diameter . MedicalThere are various surgical treatment options proposed in the literature: the 2 main surgical strategies are aneurysmorraphy and PAA resection and replacement , 16. AneThis is a retrospective, single-centre study with all their inherent limitations. We have focused on 1 specific patient collective and cannot rule out a possible selection bias regarding the PA diameter, nor can we exclude other possible influencing factors on PA diameter. Therefore, BSA should be interpreted and applied cautiously in very small or obese patients. Our diameters were measured much more precisely, and in a sufficient number of patients than in other studies. Moreover, there is an absence of model fit criteria as part of the model building steps in our exploratory approach and the treatment of missing data and data quality may be another limitation.Assessing PA diameter by taking three-dimensional centreline measurements in a representative patient cohort after contrast-enhanced, whole-body CT is a very precise method by which to define normal PA diameters. Normal mean PA diameter is 32.0 ± 4.6 mm. BSA proved to be the only influencing variable of pulmonary trunk diameter. The normal diameters and corresponding upper limits of normal measured in this study reveal that our definition of the PAA’s threshold should not be <45 mm. We also discussed the indications and surgical treatment options for PAA that effectively reduce the risk of subsequent complications.ICVTS online.This study receives institutional funding. Conflict of interest: none declared.Tim Berger: Conceptualization; Validation; Writing—original draft. Matthias Siepe: Conceptualization; Supervision; Visualization; Writing—review & editing. Björn Simon: Conceptualization; Data curation; Formal analysis; Visualization; Writing—review & editing. Friedhelm Beyersdorf: Supervision; Validation; Writing—review & editing. Zehang Chen: Formal analysis; Methodology; Visualization; Writing—review & editing. Stoyan Kondov: Data curation; Software; Visualization; Writing—review & editing. Christopher L. Schlett: Conceptualization; Supervision; Writing—review & editing. Fabian Bamberg: Supervision; Writing—review & editing. Aleksandre Tarkhnishvili: Data curation; Writing—review & editing. Salome Chikvatia: Data curation; Writing—review & editing. Martin Czerny: Visualization; Writing—review & editing. Bartosz Rylski: Conceptualization; Methodology; Supervision; Writing—review & editing. Maximilian Kreibich: Conceptualization.Interactive CardioVascular and Thoracic Surgery thanks Diego Alejandro Murillo Brito, Mateo Marin-Cuartas and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.ivab308_Supplementary_DataClick here for additional data file.


Reperfusion injury is common following primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction. In a prospective Canadian single-arm study of 15patients, the use of myocardial contrast echocardiography with high mechanical index ultrasound impulses (sonothrombolysis) initiated prior to primary PCI resulted in 7 patients with pre-PCI thrombolysis in myocardial infarction-2/3 flow (46.7%). Following reperfusion, all 15 patients had thrombolysis in myocardial infarction-3 flow, and 14 patients achieved ST-segment resolution ≥ 50% at 30 minutes post-PCI (93.3%). At 90 days, 12 patients had normal left ventricular ejection fraction ≥ 50% (80.0%). Our results demonstrate the feasibility of a novel technique to enhance reperfusion in ST-elevation myocardial infarction and provide a rationale for a randomized Canadian study. Although prompt reperfusion with primary percutaneous coronary intervention (pPCI) improves clinical outcomes in ST-elevation myocardial infarction (STEMI), abrupt recanalization often leads to reperfusion injury and microvascular dysfunction. In the first North American study, we evaluated the effects of sonothrombolysis on epicardial patency, myocardial perfusion, and left ventricular performance in STEMI.Sonothrombolysis in ST-Elevation Myocardial Infarction (SONOSTEMI) was a prospective, single-centre, single-arm study of subjects presenting within 6 hours of chest pain and found to have a STEMI requiring pPCI (NCT03092089). Following consent, sonothrombolysis was administered as early as possible prior to pPCI as previously described.Between August 2017 and June 2019, 15 subjects were enrolled (53.3% anterior STEMI) with a mean age of 61.8 ± 8.0 years, and 26.7% were female. Although this novel technique has been tested in STEMI patients in São Paulo, Brazil,


Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represents a pathology with primary pulmonary involvement and multisystemic impact, including cardiovascular injuries. The present study aimed to assess the value of clinical, biochemical, and imaging factors in COVID-19 patients in determining the severity of myocardial involvement, and to create a model that can be used toevaluate myocardial injury risk based on clinical, biochemical and imaging factors. Materials and Methods: We performed an observational cohort study on 150 consecutive patients, evaluating their age, sex, hospitalization period, peripheral oxygen saturation (SpO2) in ambient air, systolic and diastolic blood pressure, heart rate, respiratory rate, biochemical markers of cardiac dysfunction , inflammatory markers (C reactive protein (CRP), fibrinogen, serum ferritin, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα)), D-dimers, lactate dehydrogenase (LDH), myoglobin and radio-imaging parameters. All patients underwent computerized tomography chest scan in the first two days following admission. Results: We observed elevated heart and respiratory rates, higher systolic blood pressure, and a lower diastolic blood pressure in the patients with cardiac injury; significant differences between groups were registered in TnI, NT-proBNP, LDH, CRP, and D-dimers. For the radiological parameters, we found proportional correlations with the myocardial injury for the severity of lung disease, number of pulmonary segments with alveolar consolidation, number of pulmonary lobes with pneumonia, crazy paving pattern, type of lung involvement, the extent of fibroatelectatic lesions and the mediastinal adenopathies. Conclusions: Myocardial injury occurred in 12% of patients in the study group. Ground glass opacities, interstitial interlobular septal thickening (crazy paving pattern), fibroatelectasic lesions and alveolar consolidations on CT scan were correlated with myocardial injury. Routine lung sectional imaging along with non-specific biomarkers  can be further valuable in the characterization of the disease burden, thus impacting patient care. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exerts a primary pulmonary involvement; however, it also affects the cardiovascular system, and has an important impact on patient outcomes . AlthougThe pulmonary involvement patterns found in patients with COVID-19 are represented by ground-glass opacities with or without thickened intralobular septa, alveolar consolidation, and fibroatelectatic lesions. Since the outbreak of the pandemic, the ground-glass opacities have been described as hazy areas with increased density in lung parenchyma, which do not obscure bronchial or vascular structures, and it has been hypothesized that they occur due to partial filling of airspaces and initial interstitial thickening . Post-moThe present study aimed to assess the value of clinical, biochemical and imaging factors (computerized tomography of the thoracic segment) in COVID-19 patients in determining the severity of myocardial involvement at admission, and to create a model that can determine the risk of myocardial injury based on clinical, biochemical and imaging factors at admission. We performed an observational cohort study on 150 consecutive patients admitted to Department 2 of the National Institute of Infectious Diseases Prof. Dr. Matei Bals, Romania, between March 2021 and June 2021, dividing them into two groups: Group A  and Group B . 2 × 2] , and caWe considered an elevated serum value for troponin I (TnI) greater than 0.04 ng/mL as a biochemical marker of myocardial injury. All the data in this study were collected upon admission of patients, and the following inclusion criteria were used: age over 18 years, confirmed diagnosis of COVID-19 by Real Time-Polymerase Chain Reaction (RT-PCR), and chest computerized tomography (CT) on admission or within the first two days following admission. The exclusion criteria included age under 18 years, pregnant or breastfeeding women, patients with readily myocardial injury before admission orinfection with COVID-19, chronic heart disease, and chronic kidney disease . At the 2) in ambient air, systolic and diastolic blood pressure, heart rate, respiratory rate, biochemical markers of cardiac dysfunction (TnI andNT-proBNP), inflammatory markers (C reactive protein (CRP), fibrinogen, serum ferritin, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα)), D-dimers, lactate dehydrogenase (LDH), myoglobin and radio-imaging parameters, as described below.The following data were recorded for each participant: age, sex, hospitalization period, peripheral oxygen saturation , Grade 1 (mild pulmonary involvement: 1–5 pulmonary segments with pneumonia), Grade 2 (medium pulmonary involvement: 6–11 pulmonary segments with pneumonia), Grade 3 (severe pulmonary involvement: 12–19 pulmonary segments with pneumonia)Number of pulmonary segments with interstitial lung involvement (from 0 to 19)Number of pulmonary segments with alveolar consolidation (from 0 to 19)Number of pulmonary lobes with pneumonia ;Type of lung involvement: unilateral (1) or bilateral (2)Crazy paving pattern :Category 1 (changes are present in less than a third of pulmonary segments with ground glass lesions), Category 2 (changes are present in one-third to two-thirds of pulmonary segments with ground glass lesions) Cnd category 3 (changes are present in more than two-thirds of pulmonary segments with ground glass lesions)Vascular ectasia—Category 0 (when no vascular ectasia is noted), Category 1 , and Category 2 Fibro-atelectatic lesions: Grade 0 (no pulmonary sign of fibroatelectatic lesions), Grade 1 (associated with mild pulmonary involvement: 1–5 pulmonary segments with fibroatelectatic lesions), Grade 2 (associated with medium pulmonary involvement: 6–11 pulmonary segments with fibroatelectatic lesions), and Grade 3 (associated with severe pulmonary involvement: 12–19 pulmonary segments with fibroatelectatic lesions);Mediastinal adenopathy: presence or absence of adenopathy measuring more than 1 cm in the short axisPericardial effusion (present or absent)Pleural effusion The imaging characteristics were categorized as follows:Two radiologists (ED and ML) with 5 and 20 years of experience in thoracic radiology, respectively, assessed the CT scans in a consensus reading for image quality and parenchymal changes, and both radiologists were blinded towards the identity of the patients as well as their demographic, clinical, and biological parameters.Statistical Package for Social Sciences  was used for the statistical analysis. Patient data are presented as medians and quartiles  for continuous variables and as percentages for the categorical variables. The Spearman’s correlation was used to establish the independent variable that showed the highest correlation with the cardiac injury. We evaluated the impact of all parameters on cardiac injury using binary logistic regression univariate analyses with the registered data as the independent variables and cardiac injury as the dependent variable, followed by multivariable analysis.The odds ratio (OR) for the variables with statistically significant variation was calculated using logistic regression. p < 0.05) were grouped into demographic, clinical, biological, and imaging parameters. We evaluated the correlations between the recorded parameters to avoid collinearity , and where any such pairs were found, the predictor with the lowest p-value was included in theanalysis and the other was ignored. All the variables with significant association with the cardiac injury .Group A, which included patients with biochemical evidence of myocardial injury as defined above, consisted of 18 participants (12%)—10 men (55.5%) and 8 women(44.5%)—while Group B, which included patients without biochemical evidence of myocardial injury, consisted of 132 participants (88%)—65 men (49.2%) and 67 women (50.8%). The sex ratios  in Groups A and B were 1.25:1 and 0.97:1, respectively, while the median age in Group A was slightly higher than that in Group B (58 years vs. 54 years).All patients were admitted with the diagnosis of SARS-CoV-2 infection. The median duration from the first positive PCR test was 2 days for patients in both groups, with interquartile ranges (IQR), Q1 and Q3, of 1  and 2  for the patients in Groups A and B, respectively. We recorded prior SARS-CoV-2 infections in one patient in Group A (5.5%) and three patients in Group B (2.27%). Vaccination status was positive for two patients in Group A (11.1%) and 24 patients in group B (18.8%). The comorbidities of patients in both groups are presented in p-value. The median levels ofserum ferritin, fibrinogen, and IL-6 were higher in Group A than in Group B; however, similar TNFα values were recorded in both groups  from Group A and 24 patients (18.18%) from Group B. Meanwhile, most of the inflammatory markers (except CRP) did not reach a significant h groups .From CT scan results at admission, there were statistically significant differences in the severity of lung disease, number of pulmonary lobes with pneumonia, presence of crazy paving aspect, extent of fibroatelectatic lesions, and the presence of mediastinal adenopathy between participants in the two groups. The highest OR was observed in the case of mediastinal adenopathy (2.8), followed by the extent of fibroatelectatic lesions (2.4), crazy paving aspect (2.2), severity of lung disease (2.1), and the number of pulmonary lobes with pneumonia (1.6) .An increase ofone degree in the severity of lung disease increased the risk of myocardial injury by 118%; an increase ofone lobe in the number of pulmonary lobes with pneumonia increased the risk of myocardial injury by 61.8%; an increase ofone degree in the crazy paving aspect increased the risk of myocardial injury by 125%; an increase ofonedegree in the extent of fibro-atelectatic lesions increased the risk of myocardial injury by 144%; the presence of mediastinal adenopathies increases the risk of myocardial injury by 187% in the patients with SARS-CoV-2 pneumonia.D-dimers showed the highest correlation with myocardial injury (Spearman’s rho = 0.322), followed by NT-proBNP, CRP, and LDH .For the radiological parameters, a proportional correlation with myocardial injury was observed with the severity of lung disease, number of pulmonary segments with alveolar consolidation, number of pulmonary lobes with pneumonia, crazy paving pattern, type of lung involvement, extent of fibroatelectatic lesions and the mediastinal adenopathies.p-value < 0.001.LDH, D-dimer levels, extent of fibroatelectatic lesions, and presence of mediastinal adenopathieswere found to be valuable in predicting myocardial injury in COVID-19 patients, as shown in the multivariable logistic regression model depicted in Based on the data in From this study, the extent of interstitial pneumonia and superimposed interlobular septal thickening (“crazy paving pattern”), vascular ectasia, pulmonary lobes with pneumonia, pulmonary segments with alveolar consolidation, and pleural effusion were observed in patients with myocardial injury.Ground-glass opacities are the most common imaging findings in COVID-19 in medical literature . This isThickened intralobular septa generally suggest lymphocytic infiltration. Therefore, due to direct lung injury in COVID-19, interstitial lung edema usually indicates an increase in pulmonary vascular permeability that results in the movement of fluid to the interstitial compartments . HoweverFibroatelectatic lesions, which increase the vascular resistance due to lung fibrosis , were moThe presence of mediastinal adenopathy was more prevalent among Group A participants. Therefore, we hypothesize that mediastinal adenopathy may follow extensive lung damageand may reveal bacterial suprainfection or an excessive inflammatory response. The accumulation of lymphocytes in the coronary microcirculation may increase coronary resistance to flow, trigger coronary vasospasm, and induce cardiomyocyte necrosis .The prevalence of pericardial effusion among COVID19 patients has been reported to vary between 4.6% and 90.7% in critically ill patients and was reported as an incidental finding on CT scans; pericardial effusion found in severe cases of COVID-19 may be associated with myocardial dysfunction and an increase in overall mortality by 60% compared to cases without pericardial involvement . From thTissue damage can generally be indicated by elevated levels of cytolytic enzymes, including LDH, and although lacking cardiac specificity, LDH has been shown in our current study to correlate with myocardial injury. Recent studies have indicated a higher risk of negative clinical prognosis and higher mortality in patients with elevated LDH, indicating myocardial injury by a general inflammatory response with premature cell death, and transitory or definitive cardiac cell ischemia due to thrombus formation, mainlyin conditions involving endothelial dysfunction ,19. AlthSome studies have shown the importance of D-dimers in the diagnosis of myocardial injury and acute coronary syndrome . SimilarAlthough TnI and NT-pro-BNP are widely used as markersof myocardial injury, they are not fully specific. Therefore, additional markers such as serum valosin-containing protein (VCP), lectin mannose-binding 2 (LMAN2), and calpain-1 catalytic subunit (CAPN-1) should be used if available. These show a diagnostic specificity above 60% compared to CK-Mb (43.4%) and TnI (34.7%) ,28.Various types of viruses including Coxsackie B, enterovirus, HIV, parvovirus, and herpesvirus have been found to show cardiac involvement. After entering into cardiomyocytes and activating the innate immunity, the virus replicates and activates the acquired immune response, followed by disease resolution or further complications manifesting as dilated cardiomyopathy (enteroviruses), cardiomyocytes necrosis (Coxsackie B), and compromise of the systolic function. Not all myocardial injuries are exerted directly, for instance, parvovirus B endothelial damage may occur with diminished myocardial perfusion and ventricular dysfunction .In HIV infection, the involvement of the myocardium is usually multifactorial—usually by a direct invasion of cardiomyocytes by the virus. However, HIV infection may be associated with other viral infections, drug-related cardiac toxicity, nutritional deficiencies, and prolonged immunosuppression . ChronicIn a study conducted on 106 autopsied hearts Matsumori et al.  identifiCOVID-19 myocarditis seems to have distinct inflammatory characteristics that distinguish it from other viral etiologies, with a wide variety of presentations ranging from dyspnea and chest pain to acute heart failure and possibly death . The maiThe administration of steroids is considered beneficial in the management of COVID-19 , becauseStudy limitations: No cardiac ultrasound was available for use in the management of patients on admission at the hospital, meanwhile, more cardiac measures such as MRI and echocardiography may be helpful for comprehensively estimating the extent of myocardial injury. Since cTnI and NT-pro-BNP may not be fully specific or sensitive for diagnosing myocardial injury, additional markers (such as VCP or endoplasmic reticulum stress-related secretory proteins) should be used if available.The results in this study are descriptive and have no prospective observation period; therefore, the obtained results need to be validated by further prospective studies and confirmed on larger samples. The present study only assessed the value of clinical, biochemical and imaging factors in determining the severity of myocardial involvement, without demonstrating specific pathways for cardiac injury.This study showed that myocardial injury occurred in 12% of patients in the study group, and that routine lung sectional imaging along with non-specific biomarkers , can provide further value in the characterization of the disease burden, including myocardial injury, thus impacting patient care.


Heart failure (HF) is a challenging situation in healthcare worldwide. Secondary mitral regurgitation (SMR) is a common condition in HF patients with reduced ejection fraction (HFrEF) and tends to be increasingly associated with unfavorable clinical outcomes as the severity of SMR increases. It is worth noting that SMR can deteriorate dynamically under stress. Over the past three decades, the characteristics of dynamic SMR have been studied. Dynamic SMR contributes to the reduction in exercise capacity and adverse clinical outcomes. Current guidelines refer to the indication of transcatheter edge-to-edge repair (TEER) for significant SMR based on data from the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial if symptomatic despite optimal guideline-directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT), but nonpharmacological treatment for dynamic SMR remains challenging. In HFrEF patients with LV dyssynchrony and dynamic SMR, CRT can improve LV dyssynchrony and subsequently attenuate SMR at rest and during exercise. Also, a recent study suggests that TEER with GDMT and CRT is more effective in symptomatic patients with HFrEF and dynamic SMR than GDMT and CRT alone. Further studies are needed to evaluate the safety and efficacy of nonpharmacological treatments for dynamic SMR. In this review, current evidence and challenges for the future of dynamic SMR are discussed. Heart failure (HF) is a challenging situation in healthcare worldwide –3. HF wiIt is worth noting that SMR can deteriorate dynamically according to changes in hemodynamics . The chaThis review summarizes current evidence and challenges for the future of dynamic SMR in light of the mechanisms of dynamic SMR, its prognostic value, and its potentially effective treatment options.The mitral valve apparatus is intricately comprised of several components, including the mitral annulus, anterior and posterior mitral leaflets, chordae tendinae, anterolateral and posteromedial papillary muscles, and adjacent LV wall. MR can be regulated based on an exquisite balance among these components during systole. In SMR, tethering and closing forces of the mitral valve during systole are essential to understand the intricate mechanism. The tethering force is affected by LV dilatation, LV sphericity, LV regional wall motion abnormalities, papillary muscle displacement, papillary muscle dyssynchrony, papillary muscle asymmetry, annular dilatation, and annular flattening. The closing force is decreased due to LV contractility impairments, LV dyssynchrony, increased left atrial (LA) pressure, and decreased mitral annular contraction.Over the past three decades, the characteristics of dynamic SMR have been studied –13. Prev2 and VE/VCO2 slope and that the rate of exercise termination is higher in patients with dynamic SMR (ΔEROA ≥0.13 cm2 during exercise) than in those without dynamic SMR (2 during exercise) was less than that of patients without dynamic severe SMR  were shown to be unfavorable by Suzuki et al. /angiotensin II receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers (BB), mineralocorticoid receptor agonists (MRA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i); these drugs should be titrated to the maximum tolerated doses in all patients with HFrEF regardless of the presence of SMR –10. The A meta-analysis of three cardiac magnetic resonance imaging trials reported that SGLT2i therapy in patients with HFrEF was not significantly associated with reverse cardiac remodeling, including left ventricular ejection fraction, end-systolic volume, and end-diastolic volume; however, there was a tendency toward the improvement of these parameters .In HFrEF patients with persistent severe SMR, GDMT should be optimized as much as possible; however, such patients often suffer from either residual or worsening HF symptoms or undergo repeat HF hospitalization. Thus, when these patients have symptoms despite optimal GDMT, current guidelines recommend nonpharmacological treatment, including CRT and TEER (if applicable), after appropriate revascularization for significant coronary artery disease. However, there remains a matter for consideration in terms of nonpharmacological treatment for dynamic SMR in patients with HFrEF. Then, the nonpharmacological treatment of dynamic SMR is discussed below with a focus on CRT and TEER.In HFrEF patients with LV dyssynchrony, CRT can suppress LV dyssynchrony and subsequently improve LV hemodynamics while attenuating MR at rest and during exercise  20, 22), 2220, 2Also, it was (reportedly) possible to induce a left bundle branch block (LBBB) during exercise by increasing the heart rate of HFrEF patients with non-LBBB at rest . Rate-re2 during exercise) refractory to treatment with optimized GDMT and CRT if applicable (2) at rest but significant SMR (the EROA of 0.38 ± 0.10 cm2) during exercise, had a significantly higher rate of HF-related hospitalization and all-cause mortality than those in the TEER group. This suggested that resting SMR in patients with HFrEF is potentially underestimated unless ESE is performed and, consequently, even a non-significant resting SMR can bring about adverse clinical events if medically treated. In addition, this study addressed the association of EROA of SMR with left ventricular end-diastolic volume at rest and during exercise. In the study patients, EROA and left ventricular end-diastolic volume increased significantly during exercise, and as a result, the relationship between EROA in the study and left ventricular end-diastolic volume during exercise was similar to that in the COAPT study. Thus, ESE may be useful to figure out symptomatic patients with HFrEF who have potentially disproportionate dynamic SMR and are expected to receive adequate benefit from TEER.In patients with HFrEF and dynamic SMR, it may be possible that HF symptoms remain or recur with dynamic SMR refractory to optimal GDMT and CRT. In such patients, TEER can control not only the SMR at rest but also the dynamic change during exercise . Previouplicable . Of noteTEER can reduce the intensity of the symptoms of SMR and its prevalence because of the acute changes in mitral valve geometry as follows; improved coaptation area and mitral valve tethering, decreased anteroposterior diameter and area of the mitral annulus, and increased sphericity of the mitral annulus –50, all Optimal GDMT reduces the severity of SMR in patients with HFrEF , 35, 40.The study also reported that 67% of the patients who underwent TEER had either unchanged or uptitrated GDMT . Such paTEER for dynamic SMR may be expected to improve hemodynamics, mitral valve geometry, and HF symptoms, subsequently enabling patients to avoid downtitrated GDMT and gain clinical benefits as with TEER for persistent severe SMR. Thus, optimal GDMT even after TEER for dynamic SMR is also considered the crucial cornerstone of HF management considering its effect in further cardiac reverse remodeling and SMR reduction –53. FurtAlso, there are issues with ESE in patients with HFrEF and SMR; such patients can not exercise long enough to reach peak stress. Therefore, it may be difficult to compare dynamic SMRs among different patients based on certain stress criteria. Then, low-load ESE, which can be performed for a shorter time and under lower stress than conventional ESE, may be reasonable to evaluate the dynamic changes of SMR under specific stress in HFrEF patients. In such patients, it is expected that the usefulness of low load ESE will be examined in future.Dynamic SMR is associated with exercise performance impairments and adverse clinical outcomes in patients with HFrEF. In such patients, optimal GDMT and CRT are expected to ameliorate the deteriorated mitral valve apparatus, which subsequently leads to improvements in the dynamic SMR. Dynamic SMR can be residual or recurrent even after administering the appropriate treatments above. In such cases, other invasive treatment options, including TEER, may be indicated considering the effectiveness of TEER for dynamic SMR. CRT and TEER, along with GDMT, can improve deteriorated mitral valves and LVs, left ventricular dynamics, HF symptoms, exercise tolerance, and clinical outcomes. Even after obtaining such clinical benefits from CRT and TEER, GDMT regimens should be re-evaluated and reinforced as long as patients are tolerated to aim at further cardiac reverse remodeling and the reduction and prevention of dynamic SMR, subsequently leading to the amelioration of exercise tolerance and clinical outcomes.HO and MI drafted the manuscript and prepared the figures. TN, SN, and YA revised the manuscript. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


As variantes patogênicas mais frequentes são p.Arg302Gln e p.Asn488Ile.1 Devido à raridade da condição, a maioria das publicações consiste em pequenas séries de casos ou relatos de casos, com poucas exceções.3 Nenhuma das publicações anteriores relata especificamente os achados de imagem do ventrículo direito nessa condição.O gene PRKAG2 codifica a subunidade reguladora gama 2 da proteína quinase ativada por monofosfato de adenosina (AMPK). A AMPK tem um papel central na homeostase da energia celular. A variação patogênica no PRKAG2 causa uma síndrome autossômica dominante composta por hipertrofia ventricular, arritmias supraventriculares, pré-excitação eletrocardiográfica e anormalidades do sistema de condução.6 Pena et al.,7 fornecem um breve relatório com foco no ventrículo direito (VD), usando a mesma coorte, na edição atual desta Revista.Expandindo seu trabalho anterior, onde os achados de ecocardiografia 3D e imagem de strain do ventrículo esquerdo foram descritos em uma coorte de 30 pacientes com síndrome PRKAG2,Achados relevantes incluem uma alta prevalência de hipertrofia do VD (presente em 27 de 30 pacientes), uma redução mais significativa do strain basal do ventrículo direito em comparação com os segmentos médio e apical e uma fração de ejeção do VD anormalmente baixa em 17 pacientes (que é inferior a 35% em 7). É importante ressaltar que apenas 4 pacientes apresentaram aumento das pressões sistólicas da artéria pulmonar, portanto, não parece que as anormalidades do VD sejam secundárias ao aumento das pressões de enchimento à esquerda. Os achados esperados incluíam pacientes com marca-passo com pior fração de ejeção do VD e pior deformação miocárdica e uma correlação entre o strain ventricular direito e a fração de ejeção.5 O estudo também mostrou alta prevalência de disfunção sistólica do VD, com consequências clínicas e prognósticas potencialmente significativas. Investigações anteriores mostraram que a hipertrofia do VD na CMH foi correlacionada com um escore de risco de morte súbita cardíaca calculado aumentado e independentemente relacionado à presença de arritmias ventriculares.8 O próximo passo relevante será a investigação do impacto clínico desse envolvimento do VD em termos de desfechos na síndrome PRKAG2.Esses achados confirmam a impressão de hipertrofia biventricular como característica dessa condição, em comum com outras doenças metabólicas. PRKAG2 gene encodes the adenosine monophosphate-activated protein kinase (AMPK) gamma 2 regulatory subunit. AMPK has a central role in cellular energy homeostasis. Pathogenic variation in PRKAG2 causes an autosomal dominant syndrome comprising ventricular hypertrophy, supraventricular arrhythmias, electrocardiographic pre-excitation and conduction system abnormalities.3 The genetic background of this syndromic presentation was discovered in 2001.4. Histologically there is myocyte glycogen accumulation, and the typical pattern of hypertrophy is usually described as biventricular and concentric, similar to other metabolic phenocopies of hypertrophic cardiomyopathy (HCM),5 with systolic dysfunction as another possible “red-flag” feature. The more frequent pathogenic variants are p.Arg302Gln and p.Asn488Ile.1 Due to the condition’s rarity, most publications consist of small case series or case reports, with few exceptions.3. None of the previous publications specifically report right ventricular imaging findings in this condition.The 6 Pena et al.7 provide a short report focusing on the right ventricle (RV), using the same cohort, in the current edition of this Journal.Expanding on their previous work, where 3D echocardiography and strain imaging findings of the left ventricle were described in a cohort of 30 patients with PRKAG2 syndrome,Relevant findings include a high prevalence of RV hypertrophy (present in 27 out of 30 patients), a more significant basal right ventricular stain reduction compared to mid and apical segments, and an abnormally low RV ejection fraction in 17 patients (which is below 35% in 7). Importantly, only 4 patients had increased pulmonary artery systolic pressures, so it does not seem that the RV abnormalities are secondary to increased filling pressures from the left. Expected findings included patients with pacemakers having worse RV ejection fraction and poorer myocardial deformation and a correlation between right ventricular strain and ejection fraction.5 The study also showed a high prevalence of RV systolic dysfunction, with potentially significant clinical and prognostic consequences. Previous investigations have shown that RV hypertrophy in HCM was correlated with an increased calculated sudden cardiac death risk score and independently related to the presence of ventricular arrhythmias.8 The relevant next step will be an investigation of the clinical impact of this RV involvement in terms of outcomes in the PRKAG2 syndrome.These findings confirm the impression of biventricular hypertrophy as a characteristic feature of this condition, in common with other metabolic diseases.