Significant aortic regurgitation (AR) leads to left ventricular (LV) remodeling; however, little data exist regarding sex-based differences in LV remodeling in this setting. We sought to compare LV remodeling and AR severity, assessed by echocardiography and cardiovascular magnetic resonance (CMR), to discern sex-based differences.Patients with ≥ moderate chronic AR by echocardiography who underwent CMR within 90 days between December 2005 and October 2015 were included. Nonlinear regression models were built to assess the effect of AR regurgitant fraction (RF) on LV remodeling. A generalized linear model and Bland Altman analyses were constructed to evaluate differences between CMR and echocardiography. Referral for surgical intervention based on symptoms and LV remodeling was evaluated.2 vs 125.6 ml/m2, p < 0.001), LV end-systolic volume index (LVESVI) , blunted LV dilation in the setting of increasing AR severity , and LV length indexed . On Bland Altman analysis, a significant interaction with sex and LV diameters was evident, demonstrating a significant increase in the difference between CMR and echocardiography measurements as the LV enlarged in women: LVEDVI (p = 0.006), LVESVI (p < 0.001), such that echocardiographic measurements increasingly underestimated LV diameters in women as the LV enlarged. LV length was higher for males with a linear effect from RF (p < 0.001), with LV length increasing at a higher rate with increasing RF for males compared to females (two-way interaction with sex p = 0.005). Sphericity volume index was higher for men after adjusting for a relative wall thickness (p = 0.033).Of the 243 patients  female), 119 (49%) underwent surgical intervention with a primary indication of severe AR, 97 (82%) men, 22 (18%) women. Significant sex differences in LV remodeling emerged on CMR. Women demonstrated significantly smaller LV end-diastolic volume index (LVEDVI) (96.8 ml/mCMR assessment of chronic AR revealed significant sex differences in LV remodeling and significant echocardiographic underestimation of LV dilation, particularly in women. Defining optimal sex-based CMR thresholds for surgical referral should be further developed.Trial registration: NA.The online version contains supplementary material available at 10.1186/s12968-022-00845-5. Chronic aortic regurgitation (AR) results in left ventricular (LV) remodeling; however, the extent of LV remodeling in patients with hemodynamically significant AR is not uniform and it is unknown as to how variation in LV remodeling may contribute to the development of symptoms , 2. CurrMuch controversy still surrounds what defines AR severity, optimal timing of intervention in the asymptomatic population, and the ideal imaging modality for AR assessment. Moreover, prior studies have demonstrated that women tend to be more symptomatic, and fewer women with severe AR are referred for surgical intervention based on LV remodeling , 7. CurrWe sought to evaluate the hypothesis that CMR quantification of AR severity and LV remodeling in patients with chronic AR can more optimally identify sex based differences in LV remodeling than echocardiography alone. Our study objectives were as follows: (1) to compare the correlation between LV remodeling and AR severity by echocardiography and CMR to discern sex-based differences; (2) to assess sex-based differences in LV remodeling; and (3) to assess sex-based differences in referral for surgical aortic valve intervention.This is a single center retrospective cohort study of consecutive patients with at least moderate chronic AR by echocardiography, who underwent CMR within 90 days of the qualifying echocardiogram between December 1, 2005 and December 3, 2019. Patients with an LVEF < 50%, acute AR, concomitant valvular lesions moderate or greater in severity, type A dissection or aortic valve endocarditis, congenital heart disease, prior cardiac surgery, hypertrophic cardiomyopathy, cardiac amyloidosis/sarcoidosis, pericardial disease, radiation heart disease, pulmonary hypertension, restrictive/dilated/ischemic cardiomyopathy were excluded. Patients with inadequate views on echocardiography for assessment of AR or LV dimensions/volume were excluded. Clinical data were entered into the electronic medical record prospectively and extracted for analysis. This study was approved by our Institutional Review Board and granted a waiver for informed consent.Comprehensive echocardiographic examination was performed for all patients using commercially available machines . LV dimensions  were measured and calculated based on the 2015 American Society of Echocardiography (ASE) guidelines . AR seveCMR was performed based on institutional protocols . Scan parameters for balanced steady state (bSSFP) imaging on the 1.5 T scanner are as follows: TR 2.7 ms, TE 1.4 ms, acquired matrix 180 × 183, flip angle 70°, temporal resolution 30 ms. Phase contrast imaging parameters for flow quantification on the 1.5 T scanner are as follows: TR 4.8 ms, TE 2.9 ms, acquired matrix 128 × 120, flip angle 12°, temporal resolution 39 ms. Scan parameters for the 3 T scanner are as follows: bSSFP imaging: TR 2.8 ms, TE 1.4 ms, acquired matrix 192 × 177, flip angle 45°, temporal resolution 53 ms. Phase contrast imaging parameters for flow quantification on the 3 T scanner are as follows: TR 4.7 ms, TE 2.7 ms, acquired matrix 128 × 110, flip angle 12°, temporal resolution 47 ms. Epicardial and endocardial borders were traced at end-diastole and end-systole, excluding the papillary muscles, from the short axis stack bSSFP cine images to determine LV volumes and LVEF. Sphericity index was calculated as the ratio of LV end-diastolic volume to the volume of a sphere with diameter equal to the LV length measured at end-diastole in the 4 chamber view, with values closer to 1 indicating greater sphericity. Relative wall thickness (RWT) was calculated as /LV end-diastolic dimension) . Phase-cClinical outcomes of aortic valve surgery (repair or replacement), and death were assessed for all patients until September 30, 2018. Outcomes were assessed by review of electronic medical records, or by phone call for patients not seen within our system in the prior three months using a script approved by our Institutional Review Board with two attempts at contact. Patients lost to follow up were censored at the time of last known contact.Continuous variables are expressed as mean ± standard deviation and categorical variables are expressed as percent. Differences in LV volumes indexed by both BSA and height, based on aortic valve morphology and sex. Non-linear regression models were built to assess the effect of RF on LV dimensions and volumes based on sex. Bland–Altman plots were constructed to assess differences in measurements between echocardiography and CMR by sex. A multivariable linear regression model was constructed to determine independent predictors of LV remodeling. Linear and nonlinear effects were considered for each continuous predictor and two-way interactions with gender were included. Sensitivity/specificity, and Youden’s index, were reported for various cut-points of CMR predictors. Statistical analyses were performed using SAS . Significance was based on a p-value of < 0.05.Two hundred forty-three patients  female patients) who had at least moderate AR on echocardiography were included in our study. Clinical demographic and imaging variables based on gender are described in Table 4% femaleThe severity of AR by echocardiography and CMR was concordant in 41% of cases; in 51% of cases AR severity was judged to be more severe by echocardiography and in 8% more severe by CMR. In female patients the two modalities agreed in 29% of cases, a significantly smaller proportion of cases, and was categorized as higher severity by CMR as compared with echocardiography in 5%. In male patients the two modalities agreed in 44%, significantly more than for females even after adjusting for valve type (p = 0.017), with 9% of men measured as having more severe AR on CMR than echocardiography , and this difference in measurement of LVEDVI between CMR and echocardiography was larger for women (p = 0.002). Multivariable models were created to determine the impact of sex on LVEDVI and LVESVI. The final models for LVEDVI by echocardiography and CMR included sex, age, heart rate, RF, and aortic valve type. Sex was a significant independent predictor of LVEDVI in both models, and men demonstrated significantly larger LVEDVI by CMR particularly in the presence of higher RF. Furthermore, significant sex interaction with CMR derived LVEDVI (p < 0.001) and LVESVI (p = 0.001) with increasing RF, such that women demonstrated a more blunted increase LV volumes in the setting of increasing RF. In regards to echocardiographic measurements, LVEDVI measured by echocardiography demonstrated the same significant sex difference . However, the sex interactions with LV volumes and RF were not present with echocardiographic measures of LV volumes. The final models for LVESVI by echocardiography and CMR included age and aortic valve type. Sex was a significant independent predictor of LVEDVI in both models, with men again demonstrating significantly larger LVESVI by CMR with increasing RF (p = 0.011), with similar findings when LVESVI was measured by echocardiography (p = 0.026).With increasing RF, both LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI) by echocardiography and CMR increased  Fig. . LVEDVI 2 demonstrated 2 × the mean difference between LVEDDI measured by CMR vs echocardiography seen in men (Table 2 demonstrated > 2 × the mean difference between LVESDI measured by CMR vs echocardiography seen in men (Table Both LV end-diastolic dimension index (LVEDDI) and LV end-systolic dimension index (LVESDI) by echocardiography and CMR increased with increasing RF  Fig. . Multivaen Table . After aen Table . The magen Table . Table 4LV length, sphericity, and RWT were measured to describe LV shape to further explore sex differences LV volumes, in the setting of similar LV diameters. LV length was longer for males (p < 0.001) and increased in a linear fashion with increasing RF in both male and female patients, (p < 0.001). However, LV length increased at a higher rate for males, as RF increased (two-way interaction with sex p = 0.005) Fig. . LV spheGiven the recent demonstration of HFR defining significant AR , 13, a u2 vs men: 143.2 ± 47.6 ml/m2, p = 0.003), LVESVI , and LV length , but LVEDDI and LVESDI by CMR were similar: women: 2.9 ± 0.4 cm/m2 vs men: 3.1 ± 0.6 cm/m2, (p = 0.754), and women: 1.8 ± 0.4 cm/m2 vs men: 2.1 ± 0.6 cm/m2, .During the follow up period, 156 patients (121 men and 35 women) underwent aortic valve surgery. Severe AR was the primary indication for aortic valve surgery in 119 patients (97 men and 22 women). Mean time from the CMR to date of surgery was 321 days, 62.2% within 6 months, with no difference between men and women. Adjusting for age, HR, RF, and aortic valve type, women who underwent aortic valve surgery with a primary indication of severe AR had significantly smaller LVEDVI  which have been shown to be > 50% lower than the standard coefficients of variability acquired by two-dimensional echocardiography . DespiteOur study demonstrates significant sex-based differences in LV remodeling, and the impact of sex on the accuracy of echocardiography to quantify LV remodeling in the presence of significant chronic AR. One prior study examining differences in sex-based LV remodeling by CMR in AR also demonstrated limited compensatory LV dilation in women with chronic AR compared to men . HoweverWhile previous research have also demonstrated sex-based differences in LVR in response to increased afterload, such as severe aortic stenosis, there are limited data regarding phenotypic differences in remodeling in response to AR, based on sex. Women in our study demonstrated significantly smaller CMR derived LV volumes, even when indexed to BSA. This significant difference was seen at all levels of AR severity, and women demonstrated a blunted increase in LV volumes with increasing AR severity. Furthermore, women in our study surprisingly demonstrated larger LVEDDI after adjusting for age, blood pressure, RF, and aortic valve morphology, while demonstrating significantly smaller LV length. Furthermore, when CMR measurements were indexed to height, rather than BSA, indexed LV diameters were significantly larger in women compared to men, despite having significantly smaller indexed LV volumes.Additionally men had consistently higher sphericity volume index than women after adjusting for relative wall thickness. These findings suggests that male LV remodeling is more consistent with a spherical phenotype and female LV remodeling is more consistent with a conical phenotype.Similar differences in phenotypic geometric remodeling have previously been described in an animal model of chronic overload . Ashikagp < 0.001, CI 5.8–7.7) and 5.9 mm , respectively [Previous studies have demonstrated sex differences in referral patterns for surgical aortic valve intervention, such that men tend to be referred for aortic valve surgery due to a dilated LV or depressed LVEF, whereas women tend to be referred in the setting of symptoms and often at an older age than their male counterparts . Our stuectively . Our dat2 [2. Thus, underestimation of LVESDI by echocardiography may lead to delayed surgical intervention and worse outcomes. Because men demonstrated a consistent underestimation of LV diameters by echocardiography, a simple correction factor could be derived for echocardiography-derived LV diameters in men. However, the difference between LV diameters by echocardiography and CMR increased with increasing dimension for women in our study, and women with LVESDI by CMR > 2.5 cm/m2 demonstrated an underestimation of LVESDI by echocardiography by an average of 0.70 ± 0.35)cm/m2. This significant discrepancy in LVESDI measurements demonstrates the impact of sex on the accuracy of LVESDI measurements in a range that has critical importance in regard to surgical referral and association of adverse post-surgical outcomes. Our findings, in conjunction with recent CMR studies by Kammalander et al. [Our study findings have important clinical implications, as two recent studies demonstrated increase in adverse post-operative outcomes and survival for patients who underwent surgical AVR with LVESDI 2.0–2.5 and > 2.5 cm/m2 , 28. Ther et al.  and Malar et al.  demonstr2 and implantable cardiac devices were excluded from our study. Therefore, we cannot exclude the presence of selection bias. Because these CMR studies were clinically indicated studies, the findings of the study may have influenced the decision to refer patients for surgical intervention. This study included a relatively small number of women; however, given the superior reproducibility of CMR measurements of LV remodeling our study is adequately powered to assess differences in LVR assessed by CMR, based on previously published data [While this study is one of the largest comparative studies of echocardiography versus CMR in patients with chronic AR, this was a single-center retrospective cross-sectional study examining patients referred for echocardiography and CMR at the discretion of the ordering provider. Echocardiographic contrast was utilized in a minority of the studies (3.6%) and thus conclusions cannot be made regarding whether the use of endocardial border definition contrast to better define the endocardial borders for measurement of LV volumes would alter the findings of sex-based differences. Furthermore, patients with an eGFR < 30 ml/min/1.73 mhed data , 30.Our study demonstrates the ability of CMR to provide accurate and comprehensive quantitative assessment of LV remodeling in the setting of chronic AR. CMR quantification of LV dilation revealed important and novel sex-based phenotypes of LV remodeling and sex differences in symptomatology in response to chronic AR. Based on our findings, CMR provides important evaluation of chronic AR, particularly in regards to the potential for determination of optimal thresholds for surgical referral, which should include sex-specific thresholds for LV remodeling. There is a critical need to derive CMR standardized thresholds for LV volumes and LV diameters, and cutoff values for categorization of AR severity, which should be also incorporated into the societal clinical guidelines for surgical referral for aortic valve intervention. Further studies are needed to determine the pathophysiology/mechanisms of blunted LV remodeling in women in the presence of chronic AR, and how these differences might impact therapeutic management and subsequent clinical outcomes.Additional file 1: Table S1. Echocardiographic and CMR Data Indexed by BSA and Stratified Based on Aortic Valve Morphology Table S2. Echocardiographic and CMR Data Indexed by Height and Stratified Based on Aortic Valve Morphology


We sought to explore the relationship between an index of left ventricular diastolic function parameters combined with left atrial strain and the diastolic function of patients with preserved ejection fraction.n = 339) were used to validate the diagnostic performance of the mitral early-diastolic inflow peak velocity (E)-to-left atrial reservoir strain ratio (E/LASr) in left ventricular diastolic dysfunction.We prospectively enrolled 388 patients with left ventricular ejection fraction (LVEF) ≥ 50%, 49 of whom underwent left heart catherization. Transthoracic echocardiography was performed within 12 h before or after the procedure. Left atrial (LA) strain was obtained by speckle tracking echocardiography. These patients served as the test group. The remaining patients (p < 0.001] in the test group (n = 49). After adjusting for age, mitral A, E/e' ratio and β-blocker use, the E/LASr ratio was an independent predictor of elevated LVEDP and showed good diagnostic performance in determining elevated LVEDP . In the validation group (n = 339), the E/LASr ratio also performed well in diagnosing elevated left atrial pressure (LAP) , while with a cut-off value of 2.7, the E/LASr ratio showed high accuracy in discriminating elevated LAP. In addition, E/LASr was a good index of excellent diagnostic utility (AUC: 0.899 to 0.996) in the categorization of diastolic dysfunction grades. Regarding the clinical relevance of this index, the E/LASr ratio could accurately diagnose HF with preserved ejection fraction (HFpEF) (0.781), especially in patients with “indeterminate” status (AUC: 0.829). Furthermore, an elevated E/LASr ratio was significantly associated with the risk of rehospitalization due to major adverse cardiac events (MACEs) within one year .Invasive measurements of LV end-diastolic pressure (LVEDP) demonstrated that the E/LASr ratio was increased in patients with elevated LVEDP [ 2.0 (1.8–2.2) vs 3.0 (2.6–4.0), In patients with EF preservation, the E/LASr ratio is a novel index for assessing elevated left ventricular filling pressure with high accuracy. Over 90% of patients with heart failure (HF) have diastolic dysfunction regardless of left ventricular ejection fraction (LVEF), and left ventricular (LV) diastolic dysfunction is the predominant pathomechanism of HF with preserved ejection fraction (HFpEF) . ImpaireThe 2016 ASE/SCAI guideline employing several parameters makes it more convenient than previous versions; nonetheless, the diagnostic quandary of “indeterminate” status for patients whose data do not neatly fulfill the algorithms is still unsolved . On the Several studies have shown that left atrial (LA) strain, especially LA strain during the reservoir phase (LASr), is impaired in the setting of LV diastolic dysfunction and correlates well with LVFP or pulmonary capillary wedge pressure, suggesting that LASr is clinically useful for estimating LVFP , 6. Howen = 339) were used to validate the results of the test group and evaluate the diagnostic performance of E/LASr in left ventricular diastolic dysfunction.We prospectively enrolled 394 patients treated at the First Affiliated Hospital of Soochow University from November 2018 to December 2019. Fifty-five of them who were suspected of having coronary artery disease or HFpEF underwent left heart catherization. LV end-diastolic pressure (LVEDP) was invasively measured by left heart catheterization. Standard transthoracic echocardiography was performed during the 12 h before or after the procedure, and LA strain was obtained by speckle tracking echocardiography. Six of the patients were excluded because echocardiographic imaging was not good enough; thus, 49 patients served in the test group. The remaining patients (The inclusion criteria were as follows: (1) LVEF ≥ 50%; (2) no severe valvular heart disease; and (3) presence of sinus rhythm. The exclusion criteria were as follows: (1) hemodynamic instability; (2) LVEF < 50%; (3) atrial fibrillation, atrial flutter, supraventricular tachycardia, or irregular ventricular rhythm; (4) severe heart valve disease: any mitral or aortic stenosis, moderate or greater tricuspid regurgitation, moderate or greater mitral regurgitation, or experience with any valvular heart surgery or interventions; (5) insufficient echocardiographic imaging; and (6) acute ST-segment elevation myocardial infarction or acute non-ST-segment elevation myocardial infarction.mean) and the ratio of E/e'mean were calculated. The maximum velocity of tricuspid regurgitation (TRmax) was measured by continuous-wave Doppler (CW) under the guidance of color Doppler from the parasternal long axis of the left ventricle or the apical four-chamber view. Researchers were blinded to the patient's LVEDP and clinical characteristics.Transthoracic echocardiographic measurements of all subjects were performed using a GE Vivid E9 or GE Vivid E95 (Norway) 2.5 MHz transducer in the left lateral decubitus position at rest. The biplane algorithm was used to measure the maximum volume of the left atrium in the standard apical four-chamber and two-chamber views before mitral valve opening for 1–2 frames. The LA maximal volume was divided by the body surface area to obtain the LA maximal volume index (LAVI). LVEF was measured in the standard apical four-chamber and two-chamber views by Simpson’s method biplane algorithm. Pulsed-wave Doppler (PW) was used to measure the peak early-diastolic (E) and peak end-diastolic (A) transmission velocity, E/A ratio, and E wave deceleration time at the level of the mitral leaflet tips from the apical four-chamber view. In the apical four-chamber view, the sampling points were placed at the levels of the basal portion of the septal and lateral mitral annulus. Tissue Doppler imaging (TDI) and PW were used to obtain the mitral annulus movement speed, and the peak value of the longitudinal movement in the early-diastolic period . Then, the mean early-diastolic myocardial velocity . The two base points of the mitral annulus and the top of the distal end of the LA were manually selected; the area of interest was adjusted to include the entire LA wall, each view was divided into six sections, and twelve sections from each patient were analyzed. The global longitudinal LA strain was measured as an average of 12 sections. The LA reservoir strain was measured as the average of the longitudinal positive peak of LA strain, which was from all LA segments  of the apical 4-chamber and 2-chamber views .The left ventricular filling pressure was measured using a 6F pigtail catheter. The invasive procedure was performed via the radial artery by an interventional cardiologist who was blinded to the echocardiography data. Before coronary angiography, transducers were balanced prior to the acquisition of hemodynamic data with zero level at the midaxillary line. After coronary angiography, left ventricular angiography was performed. The 6F pigtail catheter was reset routinely and placed in the left ventricle to obtain a stable pressure curve. Then, the ECG and left ventricular pressure curves were recorded simultaneously. Left ventricular end-diastolic pressure was measured at the QRS starting point for baseline stable left ventricular pressure curves. All parameters were averaged over three consecutive cardiac cycles. LVEDP > 16 mmHg was defined as elevated LVFP .2, and (4) TRmax > 2.8 m/s. When more than 50% of the above criteria were positive, the patients were diagnosed with LVDD, and LV diastolic function was considered normal when less than 50% of the above criteria were positive. In addition, when only 50% of the criteria were positive, patients were diagnosed as having indeterminate LV diastolic function.According to the recommendations of the 2016 ASE/SCAI guideline, 339 pat2, E/e 'mean > 14, or TRmax > 2.8 m/s) when mitral E/A ratio ≤ 0.8 and E > 50 cm/s or mitral E/A ratio > 0.8 to < 2; and normal left atrial pressure was defined as: mitral E/A ratio ≤ 0.8 and E ≤ 50 cm/s or ≥ 2 negative criteria  when mitral E/A ratio ≤ 0.8 and E > 50 cm/s or mitral E/A ratio > 0.8 to < 2.According to the recommendations of the 2016 ASE/SCAI guideline , elevatemean > 14, LAVI > 34 ml/m2, TRmax > 2.8 m/s) were negative, it suggested that the corresponding grade of diastolic dysfunction was grade I; when mitral E/A ratio ≥ 0.8 and E > 50 cm/s, or if the mitral E/A ratio was > 0.8 but < 2, and two or three of the three criteria were positive at the same time, it indicated that the corresponding grade of diastolic dysfunction was grade II; when mitral E/A ratio ≥ 2, it was diagnosed as grade III diastolic dysfunction   had good diagnostic accuracy for elevated LVEDP. The diagnostic performance of E/LASr for LVEDP > 16 mmHg is better than that of LASr  were divided into normal diastolic function , diastolic dysfunction grade I (n = 9), diastolic dysfunction grade II (n = 101) and diastolic dysfunction grade III (n = 8). There were significant differences in E/LASr among the groups , CEs Fig. .Fig. 4CoThis study aimed to evaluate the predictive value and potential clinical relevance of a new combination index, E/LASr, for elevated left ventricular filling pressure in patients with normal LVEF. We found that LASr and E/LASr were both independent predictors of elevated LVEDP. More importantly, we found that the combined E/LASr index predicts elevated LVEDP or LAP with increased accuracy. In addition, E/LASr can accurately diagnose HFpEF, particularly in patients with an “indeterminate” status. Furthermore, an elevated E/LASr ratio was significantly associated with the risk of rehospitalization due to MACEs within one year.Recently, LA function measured as LA reservoir strain (LASr) has been shown to be significantly related to invasive left ventricular filling pressure , 6, 11. Left atrium reservoir function reflects the relaxation and compliance of the left atrium and is regulated by left ventricular systolic function . The lefThis study found that combining the early-diastolic peak inflow velocity (E) of the mitral valve and left atrial reservoir strain (LASr) as a single index further improved the ability to discriminate elevated left ventricular filling pressure (AUC = 0.903) in patients with preserved LVEF with higher accuracy. The combination index E/LASr was composed of the patient’s current left ventricular filling state  and its LA function change (LASr). This reflected not only the influence of the pressure gradient between the LA and LV on LV filling but also the relaxation and compliance of the LA affected by LV diastolic function. Therefore, this index was a more comprehensive indicator for prediction of elevated left ventricular filling pressure.This study further verified the accuracy of the E/LASr ratio in evaluating left ventricular diastolic dysfunction in 339 patients with LVEF ≥ 50% in the validation group. However, the invasive LVEDP cutoff value (2.7) predicted by the E/LASr ratio in the test group was lower than the elevated LAP cutoff value (3.2) for the evaluation of the E/LASr ratio in the validation group. Previous studies have shown that in the early stages of left ventricular diastolic dysfunction, only LVEDP is elevated, while LA pressure and mean pulmonary capillary wedge pressure are still normal , 15. HowRegarding the clinical relevance of E/LASr, this study found that E/LASr can accurately diagnose HFpEF in the validation group, and even among patients classified as "indeterminate diastolic function", it can accurately distinguish patients with HFpEF. This shows that the E/LASr ratio added the value of supplementary diagnosis to the 2016 guidelines, especially for the diagnosis of HF in gray areas with indeterminate diastolic function. In addition, in this study, patients with an elevated E/LASr ratio had a significantly increased risk of MACEs. To a certain extent, this is consistent with the results of some recent studies. Braunauer et al. found that an elevated E/LASr ratio was significantly associated with worse functional capacity and HF hospitalization at 2 years . A studyThis study has several limitations. First, the sample size for invasive measurement of left ventricular filling pressure is limited, and it is necessary to increase the sample size for multicenter studies to further verify our results. Second, the left atrial strain measured by speckle tracking imaging is defined as the absolute strain value of the three phases of the left atrium, and this study measured and analyzed only the left atrial reservoir strain. Third, because patients with atrial fibrillation lack effective atrial contraction and patients with severe mitral stenosis or mitral regurgitation have an abnormally enlarged left atrium, we did not include such patients. Finally, the clarity of echocardiographic images affects the repeatability and credibility of the left atrial strain results. Therefore, the acquisition of left atrial images and analysis of strains require more skilled operators. However, an increasing number of studies have confirmed that left atrial strain may be a powerful indicator for evaluating left ventricular diastolic function, which makes it possible for left atrial strain to be included in the diagnosis and classification of left ventricular diastolic dysfunction in the future.The results of this study indicate that a novel combination index (E/LASr) may be a more accurate indicator in predicting elevated LVFP and assessing diastolic dysfunction in patients with preserved EF. This indicator can not only add complementary diagnostic value to the 2016 ASE/SCAI guideline but also has potential clinical relevance for adverse cardiovascular events, which is worthy of further study.


Heart failure (HF) is a clinical syndrome defined by specific symptoms and signs due to structural and/or functional heart abnormalities, which lead to inadequate cardiac output and/or increased intraventricular filling pressure. Importantly, HF becomes progressively a multisystemic disease. However, in August 2021, the European Society of Cardiology published the new Guidelines for the diagnosis and treatment of acute and chronic HF, according to which the left ventricular ejection fraction (LVEF) continues to represent the pivotal parameter for HF patients’ evaluation, risk stratification and therapeutic management despite its limitations are well known. Indeed, HF has a complex pathophysiology because it first involves the heart, progressively becoming a multisystemic disease, leading to multiorgan failure and death. In these terms, HF is comparable to cancer. As for cancer, surviving, morbidity and hospitalisation are related not only to the primary neoplastic mass but mainly to the metastatic involvement. In HF, multiorgan involvement has a great impact on prognosis, and multiorgan protective therapies are equally important as conventional cardioprotective therapies. In the light of these considerations, a revision of the HF concept is needed, starting from its definition up to its therapy, to overcome the old and simplistic HF perspective. Heart failure (HF) is a clinical syndrome characterised by specific symptoms and signs due to structural and/or functional heart abnormalities, which lead to insufficient cardiac output and/or increased intraventricular filling pressure ,2.Currently, in Europe, HF incidence reaches 5 cases for 1000 people ,4, with In August 2021, the European Society of Cardiology (ESC) published the new guidelines for the diagnosis and treatment of acute and chronic HF ,14,15,16Recently, an innovative approach to HF based on phenotypes has been proposed. The use of phenotypes, across the HF spectrum, to categorise HF patients certainly represents a practical approach to bring order to HF complexity . AlthougAccording to the latest ESC Guidelines , HF is cThe LVEF-based classification has a lot of limits. Firstly, it does not consider the pathophysiological mechanism and specific aetiology underlying HF ,11. MoreFrom an echocardiographic point of view, LVEF represents only one of the parameters needed to define left ventricular function, but other parameters may be also required, especially now that the HFpEF prevalence is growing . In factSeveral trials evaluated the effect of cardiopoietic stem cell therapy in the treatment of HF ,38,39,40To overcome the limits and pitfalls of the simplistic and categorical LVEF-based classification, other approaches have been proposed.The new Universal Definition and Classification of Heart Failure  proposesAnother approach based on a new HF perspective has been proposed . HF is dThe staging systems introduced with the Universal Definition and Classification of Heart Failure  and the According to symptom onset modalities, two HF types have been identified : (i) acuThe New York Heart Association (NYHA) classification is a functional scale based on HF symptoms. NYHA classification is the oldest classification used for HF, which is based on the evaluation of symptom severity and the ability to sustain effort. It has a prognostic value , with anHF first involves the heart, but it progressively becomes a multisystemic disease, leading to multiorgan failure and death. In these terms, HF is comparable to cancer: (i) the heart involvement may be considered as the primary neoplastic lesion; (ii) lungs represent the lymph nodes of the heart; (iii) kidneys, liver, bone marrow and nervous central system involvement is comparable to metastasis spread . As in cGiven this scenario, LVEF-based classification , new claFrom a pathophysiological point of view, other parameters should be considered, beyond LVEF and NYHA classification. Beyond a simplistic categorical classification, there are complex haemodynamic parameters and circulating biomarkers which are common to several HF phenotypes and not always related to LVEF and NYHA classification .HF patients may express a normal or reduced cardiac output . MoreovePulmonary capillary wedge pressure (PCWP) is a haemodynamic parameter to evaluate left ventricular filling pressure, which is conventionally increased when its value is ≥ 15 mmHg, at rest. Patients with HFpEF often show increased PCWP, which is frequently associated with high central venous pressure (CVP) values . HoweverPCWP evaluation is a precious haemodynamic parameter and an important prognostic predictor. It is useful for the evaluation and management of HF patients . Other p™ HF system [In this setting, heart catheterisation has very restricted indications in current Guidelines , althougF system ,67. OtheF system ,69,70 trF system ,69, and The haemodynamic stress that occurs in HF may also be non-invasively assessed with natriuretic peptides evaluation . The synRecently, the 2021 guidelines for the diagnosis and treatment of acute and chronic HF ; (ii) obAlthough a multidrug treatment approach is suggested right after HFrEF diagnosis, a relevant problem is forgotten: the treatment adherence. There is clear evidence that adherence to therapy is related to a better prognosis, with a lower number of HF hospitalisations and cardiovascular deaths in chronic HF patients ,86. HoweThe recently proposed phenotypic-based approach  suggestsLastly, the therapeutic decision cannot disregard comorbidities, which play a determining role in the HF prognosis and treatment efficacy. Cachexia and frailty, which are present in almost half of patients with HFrEF and in a consistent number of HFpEF patients, are linked with a worse quality of life and exercise capacity . They alAn extensive revision of the current HF paradigm is required, from the definition to therapy, due to the limitations exposed . The evaIn conclusion, given the HF complexity, a personalised and pragmatic approach to HF patients is required. A transition from a cardiocentric to multisystemic view and from an initial phenotypic classification to a subsequent, well-reasoned, pathophysiological approach may be appropriate to overcome the limitations of current HF perspective.


The diagnostic value of cardiac magnetic resonance imaging (MRI) employing the 2018 Lake Louise criteria in pediatric and adolescent patients with acute myocarditis is undefined.To evaluate the diagnostic value of the Lake Louise criteria in pediatric and adolescent patients with suspected acute myocarditis and to show the utility of cardiac MRI for follow-up in this patient cohort.t-test were used for statistical analysis.Forty-three patients (age range: 8–21 years) with suspected acute myocarditis and 13 control patients who underwent cardiac MRI were retrospectively analyzed. T2-weighted and late gadolinium enhancement imaging were performed in all patients. T1 and T2 mapping were available in 26/43 patients (60%). The Lake Louise criteria were assessed. In 27/43 patients (63%), cardiac MRI follow-up was available. Receiver operating characteristic analysis, Pearson’s correlation coefficient and paired Student’s P=0.033). T2 relaxation times were higher in patients with admission to the intermediate care unit and were associated with the length of intermediate care unit stay . Cardiac MRI markers of active inflammation decreased on follow-up examinations .In the total cohort, the Lake Louise criteria achieved a sensitivity of 86%  and a specificity of 100% (95% CI: 79–100%) for the diagnosis of acute myocarditis. In the subgroup of patients with available mapping parameters, the diagnostic performance of the Lake Louise criteria was higher when mapping parameters were implemented into the score (area under the receiver operating characteristic curve: 0.944 vs. 0.870; The Lake Louise criteria have a high diagnostic performance for the diagnosis of acute myocarditis and are a valuable tool for follow-up in pediatric and adolescent patients. The mapping techniques enhance the diagnostic performance of the 2018 Lake Louise criteria.The online version contains supplementary material available at 10.1007/s00247-021-05169-7. Acute myocarditis is an inflammatory disorder of the myocardium primarily caused by infections, autoimmune processes, systemic diseases, drugs or toxins and can affect both adults and children . BecauseThe purpose of this cardiac MRI study was to evaluate (1) the diagnostic performance of the 2018 Lake Louise criteria for acute myocarditis in pediatric and adolescent patients and (2) to assess the value of cardiac MRI for follow-up of the disease.This retrospective, case-control study was approved by the institutional ethics committee and the requirement for written informed consent was waived. Patients with clinically defined acute myocarditis and control patients were included in this study. The department’s registry was searched for children and adolescents  who hadAll investigations were performed on a clinical whole-body MRI system . For signal reception, a 32-channel torso coil with digital interface was used. ECG-gated steady state free precession cine images were acquired in short-axis, four-chamber and two-chamber views. T2-weighted short tau inversion recovery (STIR) sequences were acquired in short-axis, two-chamber and transversal views to visualize myocardial edema and calculate the T2 signal intensity ratio. Late gadolinium enhancement imaging was based on segmented inversion recovery gradient echo sequences in short-axis, two-chamber and four-chamber orientation. Cardiac MRI protocol consisted of myocardial T1 and T2 mapping acquired in end-diastole in apical, midventricular and basal short-axis views. Post-contrast myocardial T1 maps were performed 10 min after contrast injection in the same orientation. T1 mapping was based on a standard 3(3)3(3)5 modified Look-Locker inversion recovery (MOLLI) acquisition scheme . A 6-echImages were analyzed by two radiologists  using dedicated software . Readers were blinded to the clinical information. All volumes and masses were indexed to body surface area using the Mosteller method. Visual analysis of T2 STIR and late gadolinium enhancement images was evaluated separately by consensus agreement of the two readers for focal myocardial hyperintensity as markers for myocardial edema and necrosis, respectively. Semiquantitative analysis allowed for determination of quantitative T2 signal intensity ratio  , 14. Myot-test. Dichotomous variables were compared using the Fisher exact test. For intraindividual comparisons, the paired Student’s t-test and McNemar’s test were used. Correlation analysis was performed using Pearson’s correlation coefficient. A receiver operating characteristic (ROC) analysis was performed to calculate area under the curve (AUC). Optimal cutoff values were determined using the Youden index and sensitivities and specificities were calculated. Differences between ROC curves were tested using the DeLong method. The level of statistical significance was set to P<0.05.Prism , SPSS Statistics  and MedCalc  were used for statistical analysis. The Kolmogorov-Smirnov test was applied to assess normality. Continuous patient characteristics are presented as mean±standard deviation or as absolute frequency. Continuous variables between the two groups were compared using the Student’s Fifty-nine subjects, 43 patients with acute myocarditis  and 16 age-matched control patients  were included in this study (Table P=0.32), left ventricular end-diastolic volume index , or cardiac index  between patients with acute myocarditis and control patients (Table P<0.001). Focal high intensities on T2 STIR images were detected in 32/43 (74%) patients with acute myocarditis , and T2 signal intensity ratio was elevated in the myocarditis group compared to the control group . Late gadolinium enhancement in a nonischemic distribution was found in 36/43 (84%) patients . Positive late gadolinium enhancement was observed more frequently in patients with reduced LVEF (<55%) than in patients with preserved LVEF (≥55%) .No significant differences were observed in left ventricular ejection fraction  . No difference was observed in extracellular volume fraction values between both groups . Quantitative parameters of myocardial inflammation were higher in patients with reduced LVEF . Patients with admission to the intermediate care unit had more elevated T1  and T2 relaxation times , but no significant differences in extracellular volume fraction , LVEF  or troponin level  when compared to patients without admission to the intermediate care unit. T2 relaxation time as a parameter of myocardial edema was associated with the length of intermediate care unit stay  and inflammatory laboratory parameters . T1 relaxation times correlated with troponin levels . Patients younger than 18 years old displayed lower parameters of myocardial edema , but no difference was found in T1 relaxation time  when compared to myocarditis patients ages ≥18 years.T2 relaxation time, as a marker of diffuse myocardial edema, was higher in patients compared to controls , the 2018 Lake Louise criteria could only be applied in a limited way because mapping parameters were not available in 17/43 patients. The application of the 2018 Lake Louise criteria in the total cohort reached a sensitivity of 37/43  and a specificity of 16/16  with an AUC of 0.930. Single parameters alone showed lower sensitivity .In the total cohort (n=26/43), high diagnostic performance was achieved by T2 mapping with an AUC of 0.899 , by T1 mapping with an AUC of 0.873 , and by T2 signal intensity ratio with an AUC of 0.868 . Extracellular volume fraction had an AUC of 0.687 . In this subgroup, the 2018 Lake Louise criteria yielded a significantly higher diagnostic performance  compared to the modified 2018 Lake Louise criteria with exclusion of mapping parameters . Mapping parameters allowed for the diagnosis of acute myocarditis in four additional patients. Furthermore, a combined non-contrast score of native T1 and T2 relaxation times yielded an AUC of 0.920 and a sensitivity of 22/26  and a specificity of 16/16 . Comparison of the ROC curves of this non-contrast score and the 2018 Lake Louise criteria showed no significant difference in diagnostic performance (P=0.15).In the subgroup analysis of patients with available mapping parameters (Table P=0.039). Visual myocardial edema was initially observed in 17/27 (63%) patients and was still present in 12/27 (44%) patients at follow-up. Late gadolinium enhancement was visible in 25/27 (93%) patients at baseline cardiac MRI and in 20/27 (74%) patients at follow-up. Native T1  and T2 relaxation times  decreased at follow-up. Baseline and follow-up parameters are presented in Table Cardiac MRI follow-up was performed in 27/43 patients with acute myocarditis. Mapping parameters were available in 17/27 follow-up scans. Median time to cardiac MRI follow-up was 53 days (range: 20–322 days). LVEF improved at follow-up  outperformed the original 2009 Lake Louise criteria  for diagnosis of acute myocarditis . In a peT1 mapping as a single parameter achieved high diagnostic values according to a recent meta-analysis in adults with acute myocarditis  . High seExtracellular volume fraction was implemented as another T1-based criterion in the 2018 Lake Louise criteria . It reflWhile neither extracellular volume fraction nor native T1 mapping strictly represent acute myocardial injury and are also biomarkers of myocardial fibrosis, T2 mapping has shown high sensitivity for detecting myocardial edema  and is considered specific for acute myocardial diseases , 22. TheAccording to the 2018 Lake Louise criteria, the diagnosis of acute myocarditis can be principally based on native parameters only (increased native T1 and T2 relaxation times). In our cohort, a combined native score of T1 and T2 mapping showed a high diagnostic performance , which was comparable to the original 2018 Lake Louise criteria . Although complications regarding gadolinium-based contrast agents are rare, especially since the introduction of new-generation agents, the application has several drawbacks. Peripheral intravenous insertion in children is often a traumatic procedure and extravasation may occur. Furthermore, anaphylactic reaction and nephrogenic systemic fibrosis in end-stage renal disease are extremely rare but serious complications . Given tBecause the clinical manifestation of myocarditis varies with broad spectrums of symptoms ranging from asymptomatic courses to fulminant presentations with cardiogenic shock, the diagnosis of myocarditis might be difficult. Therefore, in clinical routine, myocarditis is often diagnosed using a multimodal approach with clinical, laboratory, imaging-based and pathological parameters. Our results show correlations between quantitative parameters and disease severity. T1 and T2 values were higher in patients with reduced LVEF. Patients requiring intermediate care unit treatment presented with higher T1 and T2 relaxation times, but without significant differences in extracellular volume fraction, LVEF or troponin level, when compared to patients not requiring intermediate care unit treatment. Notably, T2 relaxation times were directly associated with the duration of intermediate care unit treatment and the extent of systemic inflammation . These findings indicate the diagnostic value of mapping parameters regarding the detection of severe courses of myocarditis, which are associated with increased mortality . FurtherOur study has some limitations. First, endomyocardial biopsy was not available as a reference standard because it is not routinely used in the diagnostic work-up of acute myocarditis at our institution due to relevant disadvantages, e.g., sampling error leading to false-negative results in focal myocarditis or its periprocedural risks, especially in sick children , 44. TheThe 2018 Lake Louise criteria including mapping parameters have a high performance for the diagnosis of acute myocarditis in children and adolescents and should be implemented into routine diagnostic work-up. Mapping parameters might be especially useful in tracking inflammatory disease activity.Online Supplementary Material 1(DOCX 20 kb)


This study aims to evidence the persistence of left ventricular (LV) systolic function (LV-SF) alterations and diastolic dysfunction (DD) in COVID-19 patients without history of cardiovascular (CV) diseases by transthoracic echocardiography (TTE). (2) Methods: 125 patients, aged under 55 years, hospitalized during the first outbreak of Covid-19 for moderate pneumonia, underwent a comprehensive cardiologic examination and TTE at 6–10 weeks after discharge. Their initial in-hospital laboratory data and thorax computer tomography (TCT) were accessed from the electronic database of the hospital. (3) Results: with TTE, we documented alterations of LV-SF and DD in 8.8% of patients and in 16.8% only patterns of DD, statistically correlated with the initial levels of creatin-kinase (CK-MB) and inflammatory factors. Multivariate regression analysis evidenced that CK-MB levels, age, and body mass index (BMI) are responsible for 65% of LV-SF decrease. (4) Conclusions: Alterations of LV-SF and DD are frequent in post-acute COVID-19 infection and are responsible for the persistence of symptoms. Elevated myocardial necrosis markers during the acute phase seem to predict subsequent alteration of cardiac performance.  COVID-19, determined by the infection with Coronavirus SARS-CoV-2), generated a global pandemic, associated with significant morbidity and mortality , generat,4. AlthoSince COVID-19 is a recent disease, the evolution of CV abnormalities has not yet been established, but as we are confronted with its second or even third outbreak, we will be facing new challenges regarding the long-term consequences of this disease. It is known that many patients experience symptoms like fatigue, reduced effort capacity, dyspnea, palpitations, or chest discomfort a long time after COVID-19, and routine cardiologic exams and TTE often reveal altered myocardial contractility and impaired cardiac performance. Terms as post-acute COVID include the persistence of symptoms from 3 to 12 weeks after the acute phase, and long COVID describes the presence of manifestations even after 12 weeks .This study aims to explore, by TTE, the alterations of the LV systolic and diastolic function in patients not yet recovered from COVID-19, at 6–10 weeks after their discharge from the hospital. Another aim is to document if the modified TTE parameters, indicating alterations of LV-SF or diastolic dysfunction (DD), are related to the magnitude of the initial immune response and levels of CK-MB, or the severity of the primary pulmonary injury, assessed on thorax computer-tomography (TCT).Study population: By analyzing the electronic database of the Hospital for Infectious Diseases from Timisoara of all 768 patients hospitalized for a SARS-CoV2 infection during the first COVID-19 outbreak (28 February and 31 July 2020) when hospitalization was mandatory for all individuals infected with SARS-CoV 2 virus, we observed that 69 patients died and 699 were discharged alive after a median in-hospital stay of 9.8 (8.3 to 12) days. Of these, 415 patients were classified according to the WHO’s criteria as mild/moderate forms of COVID-19 pneumonia [The Local Scientific Research Ethics Committee of our hospital approved the design and methodology of our study (No. 209/17 October 2020).Thorax computer tomography: based on the TCT results, all patients with pneumonia were classified at admission in the hospital in mild (<30% pulmonary injury) or moderate (30–60% lesions) forms. In the context of our study, TCT images were re-examined and pulmonary lesions were semi-quantitatively classified, according to the scoring proposed by Francone et al. in their study . Taking Echocardiographic examination: to avoid inter-observer differences, the same experienced operator performed all TTE measurements, according to guidelines recommendations . After a-the assessment of LV ejection fraction (LVEF); by the modified Simpson rule, values of LVEF < 50% being considered abnormal;-the measurement of the lateral mitral annular plane systolic excursion (MAPSE); values < 10 mm being considered pathologically;-the assessment, in Tissue Doppler imaging (TDI), of the average systolic mitral annular velocity (LV-S’); values under 0.07 m/s being considered abnormal;-the quantification of the LV global longitudinal strain (LV-GLS) was realized from apical 2-, 3-, and 4-chamber view, the region of interest being automatically generated and, after tracing the LV endocardial border, manual corrections were subsequently performed to fit the thickness of the LV myocardial wall ,21,22. VLeft ventricular (LV) systolic dysfunction was assessed from apical 4-chamber view and included:-the assessment of left ventricular mass index (LVMI); values of over 115 g/m2 for males and 95 g/m2 for females defined left ventricular hypertrophy (LVH);-left atrial volume index (LAVI); values over 34 mL were considered pathological;-in pulsed Doppler, in apical 4-chamber view, we registered the mitral inflow at the level of the mitral valve annulus and analyzed the peak early diastolic velocity (E), the late diastolic velocity (A), and the E/A ratio.-TDI was used to record the early diastolic velocity (e’) and the late diastolic velocity at the level of the septal and lateral mitral annulus. Subsequently, an average and E/e’ ratio were calculated. Type I of DD was defined by an E/A ratio ≤0.8 and E < 50cm/Sec, while type III DD was confirmed by an E/A ratio of over 2. In case of an E/A ratio ≤ 0.8, but with an E of over 50 cm/Sec, or if the E/A was between 0.8 and 2, a type II DD was considered, and was certified if at least two of the following three criteria were present: an average E/e’ > 14, LAVI > 34 mL/m2, and/or TRV > 2.8 m/Sec. In cases where only one of the three previously mentioned criteria were fulfilled, a type I DD was diagnosed .Left ventricular diastolic dysfunction (DD) comprised:-tricuspid annular plane systolic excursion (TAPSE) was measured at the level of the lateral tricuspid valve annulus in M-Mode;-tricuspid regurgitation velocity (TRV) was recorded by continuous-wave Doppler, from the apical window, at the level of the tricuspid valve;-echocardiographically determined systolic PAP (sPAP) was assessed based on the peak TRV, taking into account the right atrial pressure, determined by measuring the inferior vena cava diameter and its respiratory variations. In this study, we considered that sPAP values of ≥35 mmHg at rest indicate PH ,16 with -RV global longitudinal strain (RV-GLS) was performed in apical 4 chamber view ,26 and, Right ventricular (RV) performance was evaluated in 4-chamber view, visualizing the entire RV: A first endpoint of our study was to evaluate, in terms of cardiovascular complications, the outcome of 125 patients in whom we ruled out by history, clinical examination, and TTE a pre-existing cardiovascular condition that would have explained the presence of cardiac alterations assessed by TTE.The second endpoint was to identify the patients with alterations of the cardiac performance to refer them for further evaluation and to monitor their evolution under therapy. p < 0.05, exclusion criteria p > 0.10) to obtain the most appropriate theoretical model to fit the collected data. We considered that p values under 0.05 indicate statistically significant differences.Statistical analysis: The Statistical Package for the Social Sciences v.25  was employed to perform data analysis. We presented continuous variables as mean and standard deviation (SD) or median and interquartile range (IQR), and categorical variables as frequency and percentages. Because the results of the normality test (Shapiro–Wilk) showed a non-Gaussian distribution, we continued the analysis by using nonparametric tests. For comparing the three groups , we employed the Kruskal–Wallis test, followed by post-hoc analysis with Mann–Whitney U test and Bonferroni correction for pairwise comparisons. To compare TTE parameters, the Mann–Whitney U test was employed. Fisher’s exact test was employed to evaluate the significance of differences in the proportions of nominal variables. We employed Spearman’s correlation test to assess the potential connection between LV-GLS and E/e’ ratio with other TTE parameters and laboratory results. We built several multivariate regression models to assess the individual impact of several confounding factors on the variance of continuous variables, and the model was validated based on the accuracy of prediction and R squared. In the final regression equations, the predictors were accepted according to a repeated backward-stepwise algorithm . All had a recent hospitalization for a mild/moderate SARS-CoV-2 pneumonia, confirmed by RT-PCR and TCT during the first outbreak of COVID-19 less than 10 weeks before. None of them had severe respiratory insufficiency requiring mechanical ventilation or ICU stay. Of those patients, 29.6% were overweight and 28.8% had obesity. When they were contacted by phone, 57 of them (53.6%) still reported symptoms, most frequently fatigue, dyspnea, and palpitations. After the inclusion in the study, patients’ laboratory data were accessed from the electronic database of the hospital, and their TCTs were re-analyzed and a global TCT COVID score calculated. All these results are displayed in Therapy during hospitalization was prescribed according to current recommendations with protease inhibitors , lopinavir/ritonavir-AbbVie, Ludwigshafen, Germany), antibiotics  or azithromycine-Sandoz, Targu-Mures, Romania), corticoids , and anticoagulants  or rivaroxaban-Bayer AG, Leverkusen, Germany), continued 40 days after discharge in a prophylactic dose.At the inclusion in the study, at 6–10 weeks after the discharge from the hospital, a detailed clinical exam and a comprehensive TTE were performed in all patients that should have recovered from COVID-19 at that time. Values are presented in p < 0.001). Referring to our study group, in 93 patients (74.4%), TTE parameters characterizing the LV systolic and diastolic function were within normal limits, although we identified in 7 individuals (4 men and 3 women) mild LVH and another 4 patients had borderline values of RV-GLS . It is tIn a subset of 11 patients (8.8%), we identified alterations of LV-SF, certified by LV-GLS < 17, MAPSE < 10, and LVEF under 50 (between 36 and 48%). All of them had associated DD: 6 of type III, with E/A > 2 and 5 of type II. LVH was evidenced in 4 men and 1 woman. Other associated findings, detected in all these patients, were RVD and PH (of mild or moderate severity).In another subgroup of 21 patients (16.8%), 13 women and 8 men, with normal LV-SF, we documented the presence of DD: 6 subjects had DD of type I and 15 of type II. Ten patients (6 women and 4 men) had associated LVH, and 7 of them had mild RVD. Taking into account that all 11 patients with altered LV-SF had associated DD, the real prevalence of this dysfunction rises to 25.6%.When we examined the existence of correspondences between LV-GLS with other TTE parameters characterizing cardiac performance in all patients with altered LV-SF and/or DD, we documented, by using Spearman’s correlation, statistically significant correlations between all these TTE parameters, as well as between LV-GLS with TCT scores and laboratory data assessed at the admission in the hospital, p < 0.001, p = 0.002, and p = 0.012, respectively) and moderate ones with age, BMI, and TCT score . A strong correlation with MAPSE  was also documented, as well as moderate ones with LVEF, RV-GLS, and TRV . Referring to LV-GLS as the most sensitive parameter characterizing the LV function, if we take into account only the 11 patients with impaired LV-SF, the statistical analysis by using Spearman’s correlation, reveal statistically significant correlations with several inflammatory markers like Interleukin-6, CRP, and with CK-MB , with COVID TCT score , and with markers of inflammation determined at the admission in the hospital: CRP, interleukin-6, and fibrinogen . We evidenced moderate correlations with other parameters characterizing DD: LAVI , TRV , and the number of days until negativation of PCR (r = 0.7 p < 0.001). Although LVMI should be a factor that strongly influences DD, due to different limits for men and women, the correlation was not statistically significant.Considering that elevated values of E/e’ ratio were the most common finding in patients with DD, by using the Spearman’s correlation, the statistical analysis evidenced statistically significant correlation of the E/e’ ratio with age and BMI . For each increase of CK-MB with 1 IU/L, the risk of a reduced LV-SF augments by 1.3%. Similar results were obtained also for the E/e’ ratio.We employed in our patient group a multivariate linear regression analysis to determine the most significant independent predictor factors that could explain the occurrence of altered LV-GLS associated with DD or not. The forward stepwise method was used to build the regression model, and the best model was appreciated based on Akaike information criteria (AIC). After the adjustment for all other TTE parameters characterizing the cardiac performance as potential confounding factors, we identified that the initial values of CK-MB, more advanced age, and BMI are responsible for 65% of the reduced values of LV-GLS , and therapy with angiotensin converting enzyme (ACE) inhibitors and antiischemic agents  and in several cases beta-blockers  was initiated.The increased prevalence of CV complications in the acute phase of COVID-19 is a debated topic in numerous scientific articles ,28,29. Mp < 0.001) were evidenced between TTE parameters characterizing LV-SF, as well as DD, and the initial levels of CK-MB and several inflammatory biomarkers  supporting the hypothesis that the cytokine storm, following the acute viral injury, determines myocardial lesions that could potentially progress to fibrosis affecting the cardiac performance [The pathogeny of DD and HFpEF in COVID-19 patients represents a controversial subject, with several hypothesis being proposed: a direct viral infiltration of the myocardium, inflammation, ischemia, or subsequent fibrosis. The exacerbation of a preexisting DD or the unmasking of subclinical forms in subjects with risk factors cannot be ruled out . By seleformance .Even more concern has arisen in the last period, regarding the persistence of symptoms like dyspnea, fatigue, reduced effort capacity, in COVID-19 patients, a long time after the acute disease, when they should have totally recovered. Different terms and pathogenies have been proposed, but precise information is still missing. Few studies are referring to the evolution of CV complications in patients who had suffered a SARS-Cov-2 infection, but still have symptoms starting from 3 to 12 weeks after the acute phase, the so-called post-acute COVID-19 and even less in those who have not yet achieved their base-line health after 12 weeks, considered to suffer from the Long COVID syndrome ,32. HoweAlterations of cardiac performance are not so uncommon after COVID-19 and could explain, at least partially, the persistence of symptoms in the post-acute COVID-19 phase. Elevated myocardial necrosis markers and inflammation during the acute infection, older age, and increased body mass index seem to predict subsequent impairment of the systolic or diastolic cardiac function.


ECV at nearly all myocardial segments and a global ECV were higher in patients with AB . Only indexed left ventricular end-diastolic diameter  and global ECV  were independently associated with AB. The global ECV cut-off value of 31.05% differentiated both groups . Neither qualitative nor quantitative LGE-based assessment of replacement fibrosis allowed for the stratification of DCM patients into low or high AB. Interstitial fibrosis, expressed as ECV, was an independent predictor of AB in DCM. Incorporation of CMR parametric indices into decision-making processes may improve arrhythmic risk stratification in DCM.The current stratification of arrhythmic risk in dilated cardiomyopathy (DCM) is sub-optimal. Cardiac fibrosis is involved in the pathology of arrhythmias; however, the relationship between cardiovascular magnetic resonance (CMR) derived extracellular volume (ECV) and arrhythmic burden (AB) in DCM is unknown. This study sought to evaluate the presence and extent of replacement and interstitial fibrosis in DCM and to compare the degree of fibrosis between DCM patients with and without AB. This is a prospective, single-center, observational study. Between May 2019 and September 2020, 102 DCM patients underwent CMR T1 mapping. 99 DCM patients  composed study population. AB was defined as the presence of VT or a high burden of PVCs. There were 41 (41.4%) patients with AB and 58 (58.6%) without AB. Replacement fibrosis was assessed with late gadolinium enhancement (LGE), whereas interstitial fibrosis with ECV. Overall, LGE was identified in 41% of patients. There was a similar distribution of LGE (without AB 50% vs. with AB 53.7%;  The bulk of evidence indicates that runs of NSVT and frequent PVCs, defined as arrhythmic burden (AB), lead to an increased sudden cardiac death (SCD) risk in DCM patients2. Susceptibility to ventricular arrhythmias in DCM relies on the combined presence of an anatomic substrate  and triggering mechanisms. Profound cardiac remodeling and fibrosis provide ample substrate for the initiation of ventricular arrhythmias.Ventricular arrhythmias, including premature ventricular contractions (PVCs) and non-sustained ventricular tachycardia (NSVT), occur in 40% of patients with dilated cardiomyopathy (DCM)4. Broadly, two types of fibrosis have been identified. Replacement or scarring fibrosis develops as a consequence of local myocytes death and serves to preserve the integrity and function of the heart after injury5. DCM is typically characterized with wide-spread interstitial fibrosis given that the need for cardiac repair is minimal and, ultimately, fibrosis is a maladaptive event5.Cardiac fibrosis is typically observed in 40–60% of DCM patients7. Identification of late gadolinium enhancement (LGE) allows for the detection of areas of replacement fibrosis, which are relatively large and focal7. However, LGE cannot be used to detect and quantify interstitial fibrosis7. T1 mapping has emerged as a robust technique for the quantification of interstitial fibrosis by measuring T1 times and extracellular volume (ECV)8. In fibrotic hearts, both native T1 time and ECV increase, whereas post-contrast T1 time decreases8. T1 times and ECV have been validated against biopsy-determined collagen volume fraction11.The preferred contemporary method of assessment of cardiac fibrosis is cardiovascular magnetic resonance (CMR)14. Studies on cardiac fibrosis, utilizing either LGE-based or T1-parametric assessment showed associations between fibrosis and clinically-relevant outcomes, including arrhythmic risk17. However, the relationship between comprehensive assessment of interstitial fibrosis, by means of ECV, and AB in DCM has not been established. The primary hypothesis underlying the study was that patients with high AB would have an increased ECV, suggesting a higher amount of interstitial fibrosis. Therefore, we compared the degree of interstitial fibrosis, expressed as ECV, between DCM patients with high and low AB.Despite evidence suggesting that cardiac fibrosis is the crucial parameter influencing arrhythmic risk, current guidelines do not take fibrosis into accountp < 0.05), whereas all other parameters were similarly distributed. No gender-based differences were identified.Out of 102 initially recruited patients, 3 subjects had incomplete data such that the final study population consisted of 99 DCM patients. Eighty-eight (88.9%) patients were male, and the mean age was 45.2 ± 11.8 years. Patients were divided into those with  and without  AB. The comparison of the baseline demographic, clinical, laboratory, echocardiographic parameters, and therapies between the two groups is presented in Table LGE presence and extent were similarly distributed between the groups Table . There wp < 0.10), only indexed LVEDd and the global ECV were found to be independently associated with AB (Table p = 0.04) of discriminating AB presence  than indexed LVEDd  The proposed cut-off point of ECV of 31.05% had a higher specificity and sensitivity than indexed LVEDd cut-off point of 33.27 mm/m2 . The proposed cut-off points of ECV and indexed LVEDd had the highest accuracy   with adjustment for the presence of hypertension, systolic blood pressure, LV end-diastolic indexed diameter and loop diuretics’ daily dosage.Out of all the parameters that differentiated patients with and without AB  and for the inter-observer T1 measurements of 1.02% and 2.34% . The Bland–Altman curves are presented in the Supplementary Fig. The study findings can be summarized as follows. Patients with and without AB were indistinguishable according to numerous demographic, clinical, echocardiographic and laboratory parameters as well as baseline therapy with the exception of larger LV cavities in DCM patients with AB. Neither qualitative nor quantitative LGE-based assessment of replacement fibrosis allowed for the stratification into low or high AB. ECV in nearly all myocardial segments as well as the global ECV were larger in patients with AB. ECV and indexed LV end-diastolic diameter were independently associated with AB in DCM.14. In practice, LVEF remains the cornerstone of risk-stratification. However, LVEF has a low sensitivity and specificity for the prediction of SCD18. The DANISH study revealed that ICD implantation did not result in a reduction of SCD but was associated with an increased rate of device-related adverse events in DCM19. In the landmark meta-analysis based on 45 studies enrolling 6,088 patients, Goldberger et al. evaluated the predictive power of 12 commonly used arrhythmic risk tools. The authors reported prognostic accuracies with a range of sensitivities (28.8–91%) and specificities (36.2–87.1%) for all studied tests with the best performance for fragmented QRS and T-wave alternans20. In this study, the prevalence of NSVT was 45.5%, and it had moderate diagnostic accuracy for SCD prediction 20.Accurate arrhythmic risk stratification is a cornerstone of optimal management of the DCM patients. However, current guidelines select DCM patients for implantable cardioverter-defibrillator (ICD) implantation for primary prevention of SCD based on only three parameters: symptoms (according to NYHA class), persistent LVEF ≤ 35% despite of at least 3 months of optimal medical therapy and an expected survival longer than 1 year14. However, in almost all contemporary DCM-dedicated studies on SCD, enrolled patients are in their sixth or even seventh decade, e.g. Dawson et al.—mean age of 48–57 years, aus dem Siepen et al.—55–58 years, Nakamori et al.—56 ± 16 years, Cui et al.—49.3 ± 16, Køber et al.—63–64 years, Goldberger et al.—52.8 ± 14.5 years, Nakamori et al.—52 years (range 19–89), Neilan et al.—55 years, Kodama et al.—61 ± 12 years23. Our study is one of the very few in which the mean age of DCM patients is much younger (45.2 ± 11.8 years) and more likely reflects the true spectrum of DCM population. In addition, our study population of almost 100 DCM patients with T1-parametric assessment is one of the largest published cohorts as the majority of studies enrolled a smaller number of patients. Of note, all data on the associations between investigated parameters and outcomes should be interpreted with caution given the size of the studies. Thus, we focused on the established predictor of arrhythmic events—arrhythmic burden.DCM is commonly diagnosed in young adults in whom it is the primary reason for HF and SCD16. However, the majority of those studies stratified patients based on a binary classification into: LGE-present and LGE-absent groups, which is an oversimplification and gross underestimation of the true burden of cardiac fibrosis. There are several studies that quantified the extent of LGE in the context of arrhythmic risk. In one study, the amount of cardiac fibrosis, expressed as LGE extent, was found to be an independent SCD predictor. Neilan et al. reported that LGE extent was the strongest predictor of major events, including SCD and appropriate ICD therapy, and patients with LGE involving > 6.1% of LV had the highest rate of events22. It should be emphasized that LGE extent is variably measured in studies, and there is still no consensus on the best method of quantification24. In our study LGE was present in 41% of patients and LGE extent constituted approximately 4.5% of the LV. Both qualitative (LGE “+” or LGE “−”) and quantitative (LGE extent) assessments showed very similar LGE distribution in patients with and without AB. Consequently, neither LGE presence nor LGE extent were found to be associated with AB.Several studies have reported an association between LGE and ventricular arrhythmias and SCD25. Based on measurements in 3872 volunteers, normal values for ECV have been established as 25.9% (95%CI 25.4–26.5%) at 3.0-T25. Our examinations were performed at 3.0-T utilizing the MOLLI protocol; mean native T1 times in the control group were 1196.3 ± 34.8 ms in comparison to DCM patients in whom an average native T1 time was 1232.2 ± 174.7 ms. The average ECV in the control group was 23.9 ± 1.2% and the septal ECV was 26.3 ± 3.5%, whereas in our patients it was 28.7 ± 4.9% and 32.2 ± 7.7%, respectively. We also report very high reproducibility of measurements, both for intra- and inter-variability assessments. Thus, we believe our data represents high-quality measurements.CMR-based parametric mapping overcomes numerous shortcomings of LGE-based assessment of cardiac fibrosis. Crucially, T1-mapping allows for the quantification of interstitial fibrosis. In order to ensure high quality and reproducible measurements, acquired parametric data should be compared with: (1) published referral values, and (2) an internal control group. An impressive number of 5541 healthy subjects with CMR mapping were aggregated in a recent meta-analysis, which showed a mean native T1 time of 1159 ms (95%CI 1143–1175 ms) at 3.0-T for MOLLI-based protocol23. Nakamori et al. compared 50 DCM patients with a history of complex ventricular arrhythmias (ComVA) with 57 age-matched DCM patients without ComVA. The authors found that global native T1 time was significantly higher in patients with ComVA in comparison to those without ComVA (1131 ± 42 vs. 1107 ± 45 ms). Moreover, native T1 was found to be independently associated with ComVA, even after adjusting for LV function and LGE17. In the another paper, Nakamori et al. examined 115 DCM patients referred for SCD primary prevention assessment. The combination of native T1 time and the novel index—Mad-SD  showed excellent diagnostic accuracy in regard to the prediction of arrhythmic event-free survival21. Kodama et al., who studied 60 DCM patients, showed that patients with ECV ≥ 30% and QRS duration > 120 ms had a higher rate of arrhythmic events23. In the present study, we measured ECV in 16 myocardial segments, which allowed for the calculation of global ECV as well as an average of two mid-myocardial septal segments (no. 8 and 9 according to AHA classification). We observed that septal segments, regardless of anatomical location—basal, mid-ventricular or apical, had the highest ECV values, which is consistent with previous reports. This ECV gradient is common in patients with and without AB; however, all septal ECV values were significantly higher in those with AB.Since 2013, a few dozen studies utilizing CMR T1 mapping in DCM have been published. Native and post-contrast T1 times as well as ECV have been found to be associated with LV reverse remodelling and outcomes in DCM. There are only a few studies that have investigated the relationships between T1 parameters and ventricular arrhythmias in DCM7. These aforementioned conditions are infrequent and have been excluded such that ECV is believed to reflect interstitial fibrosis. It is not surprising that wide-spread interstitial fibrosis negatively affects electrical signal transmission between cardiomyocytes and may promote the development of arrhythmias. Interstitial fibrosis (i.e. increased ECV) should not be viewed as a direct mechanism of arrhythmia in a particular patient as those mechanisms are much more complex and include scar related re-entry circuit, bundle branch block re-entry or mutations of ion channels14. Thus, ECV (i.e. increased ECV) should be considered a very strong marker of ventricular arrhythmias, specifically in DCM.Until recently, it was not feasible to reliably assess and quantify interstitial fibrosis. The advent of the CMR parametric technique has dramatically changed this perspective. Nonetheless, it should be acknowledged that ECV is not a 100% specific measure of fibrosis given that other interstitial pathologies, such as oedema, protein degradation and aggregation, lipid accumulation, and deposition of iron or amyloid profoundly impact on ECV valuesIt may be time to challenge the paradigm of cardiac fibrosis in the setting of DCM. A binary classification scheme of cardiac fibrosis seems to be outdated in the era of quantitative assessment of fibrosis. Cardiac fibrosis, as almost all biological processes, is a continuum, and it is a gross assessment to dichotomize between absent and present as “present” may infer significantly different degrees of fibrosis. In the early days of CMR, when only LGE-based assessment was present, it may have been a reasonable description of results. However, in the era of quantitative assessment of fibrosis, the “degree” of cardiac fibrosis may be precisely defined. Based on ROC analysis, we found that ECV > 31% accurately stratifies patients into low and high arrhythmic risk. Cardiac fibrosis is present in both sub-groups, as ECV is already elevated in all of them (in comparison to the controls); however, it is the amount of fibrosis that increases the arrhythmic risk.Although our study is one of the largest published studies, it is a single-centre study with a relatively small number of patients. Despite the fact that CMR T1 parametric mapping is already a mature technique, several different imaging protocols exist. We relied on the most commonly-used MOLLI protocol; however, utilizing other protocols may provide slightly different results. Due to the lack of complete data from historic reports or examinations, AB was based on a 48-h Holter monitor during the index hospitalization or outpatient visit.Neither qualitative nor quantitative LGE-based assessment of replacement fibrosis allowed for the stratification of DCM patients into low or high AB. Interstitial fibrosis, expressed as ECV, was significantly higher in patients with AB. ECV alongside with indexed LV diameter were found to be the only independent predictors of AB in DCM. Incorporation of CMR parametric indices into predictive models may improve arrhythmic risk stratification in DCM.26. Our control group consisted of 11 healthy volunteers who were free of any chronic diseases.Between May 2019 and September 2020, 102 consecutive patients with a diagnosis of DCM were recruited. All patients received optimal heart failure (HF) therapy and displayed stable symptoms (New York Heart Association—NYHA I–III class) for at least 2 weeks prior to enrollment. DCM was diagnosed based on (1) the presence of impaired left ventricle (LV) systolic function  and LV dilation, and (2) the exclusion of significant coronary artery disease , primary heart valve disease, congenital heart disease and severe arterial hypertension12. The study protocol was approved by the John Paul II Institutional Review Board and the Krakow Medical Chamber Ethics Committee (reference number 7/KBL/OIL/2019). All study-related procedures were performed in accordance with the current Guideline for Good Clinical Practice and Declaration of Helsinki 2013. All patients and volunteers gave written informed consent.This is a prospective, single-centre observational study. All patients underwent detailed diagnostic work-up, including clinical evaluation, laboratory tests, electrocardiogram (ECG), 48-h Holter ECG monitoring, transthoracic echocardiography, 6-min walk test (6MWT) and CMR. The patients were on guideline-directed medical therapy for HF including beta-blockers (BB), angiotensin receptor-neprilysin inhibitor (ARNI) or angiotensin-converting-enzyme inhibitor (ACE-I), mineralocorticoid receptor antagonist (MRA) and loop diuretics8. Steady-state free precession cine images were obtained in consecutive short-axis slices covering the LV and three long-axis  slices. The CMR protocol included cine CMR, native and post-contrast T1 mapping, and LGE imaging. The LV was divided into 16-segment model described by the American Heart Association. Cardiac volumetric and functional parameters were quantified based on manual delineation of the endocardial and epicardial borders using a stack of continuous short-axis slice cine images.CMR examinations were performed at the time of the inclusion on a 3.0-T scanner . CMR studies were analysed by using Syngo.VIA software version VB 40  following the post-processing guideline from the Society of Cardiovascular Magnetic Resonance8.Consecutive short-axis LGE images covering the LV were obtained 15 min after intravenous injection of 0.1 mmol/kg of body weight gadolinium-based contrast agent. The presence of LGE was judged by three independent observers blinded to patients’ information . Fibrosis was considered present if LGE was visualized on both short- and orthogonal long-axis LGE images. The quantitative analysis of LGE extent was assessed using 5 standard deviations threshold on consecutive short-axis slices and calculated as a percentage of total LV mass (%LGE) Fig. 7,8.Figur2, matrix of 144 × 256 pixels, flip angle of 35°. Native and post-contrast T1-values were determined by drawing regions of interest (ROI) in every segment of the basal, mid-ventricular slice as well as in the centre of LV cavity for measuring T1 blood pools. ROIs were drawn in mid-wall region of the myocardial segments and were copied between native and post-contrast T1 maps  a Modified Look Locker Inversion (MOLLI) Recovery sequence before and 15 min after gadolinium-based contrast agent injection. The following typical MOLLI sequence tfi2Dl parameters were used: breath-hold TR/TE of 281/1.1 ms, slice thickness of 8 mm, FOV from 320 × 260 mm8. A blood sample was obtained on the day of scanning to measure hematocrit.Areas of LGE replacement fibrosis were included in the T1 times and ECV measurements28.Patients underwent 48-h ECG Holter monitoring . The mean, minimum and maximum heart rate, the total number of PVCs and NSVT were recorded. VT was defined as a minimum of three consecutive PVCs with a rate of ≥ 100 bpm. All recorded VTs were non-sustained. We divided the total number of PVCs during the recording by the number of analysis hours (PVC/h) and calculated the daily VT numbers by dividing the total VT number by the 2-days monitoring (VT/d). The AB was defined as the presence of VT or a high burden of PVC (≥ 30 PVCs per hour)2 test was performed for the comparison of qualitative parameters. The associations between the parameters and the AB were analysed with uni- and multivariate logistic regression methods. All parameters  were included in the regression analyses. When normality was confirmed, a Pearson correlation was performed in order to identify a potential correlation between AB predictors. Otherwise, a Spearman rank correlation was used. Due to the high correlation between ECV and native and post-contrast T1 times (R-Spearman > 0.8) and between systolic and diastolic blood pressure , only total ECV and SBP were included in the regression models. Areas under (AUC) the receiver operating curve (ROC) were calculated to assess the cut-off values of ECV for AB. The Z test was used for comparing the AUC of each prognostic scale. Agreement between measurements was assessed using Bland–Altman plots. All results were considered statistically significant when the p value was < 0.05. The Statistica package, version 13.0 , was used.All values are presented as mean ± SD or percentage where appropriate. All quantitative variables were tested for the normal distribution of data with the Shapiro–Wilk test. Comparisons of the continuous variables were conducted with a t-test when normality was confirmed, otherwise with a Mann–Whitney test. The χSupplementary Information.


A forma de onda do ECG é a expressão dos potenciais de ação transmembrana e é composta por dois processos distintos: despolarização e repolarização.11 realizaram um estudo observacional, retrospectivo, avaliando a relação entre a cicatriz miocárdica detectada por RM com contraste e vários parâmetros eletrocardiográficos de repolarização ventricular em pacientes com ICFEr. Os autores observaram medidas prolongadas do intervalo QTc, intervalo Tp-e e ângulo QRX-T frontal em pacientes com ICFEr que apresentaram cicatriz miocárdica na RM com contraste, em comparação a pacientes que não a apresentaram.Nesta edição dos Arquivos Brasileiros de Cardiologia, Erturk et al.,11Com base na análise de múltiplas variáveis, o intervalo Tp-e foi o melhor parâmetro para predizer a presença de cicatriz miocárdica. Os autores concluíram que é possível predizer essa condição utilizando parâmetros eletrocardiográficos na ICFEr.12 o que determina o intervalo QT. Estudos prévios mostraram uma forte associação entre presença de cicatriz subendocárdica e repolarização ventricular anormal em pacientes com doença arterial coronariana.13 Estudos com RM cardíaca de indivíduos da comunidade também demonstraram que a presença de cicatriz subclínica detectada por RM com contraste estava associada com maior mortalidade.14 Portanto, a repolarização ventricular anormal, detectada por ECG, pode ser útil na predição de cicatriz miocárdica subclínica e na identificação de pacientes em alto risco.Há poucos estudos sobre a relação entre a presença de cicatriz miocárdica e alterações no ECG. Modelos experimentais mostraram que a indução da formação de cicatriz subendocárdica prolonga o tempo de repolarização das células M,15 o estudo apresenta limitações, incluindo o tamanho amostral pequeno, seleção de pacientes em um único centro, e delineamento retrospectivo e observacional. Serão necessários estudos grandes prospectivos para validar os parâmetros de repolarização ventricular propostos. Os autores estabeleceram uma base sólida de informações que promoverá o avanço da área de ECG em estudos futuros.Apesar deste estudo apresentar resultados animadores que agregam importantes informações a publicações anteriores,11 também destaca a íntima relação entre fibrose miocárdica e distúrbios na condução elétrica. Existe um forte interesse em se compreender a composição da cicatriz e a instabilidade elétrica relacionada.7 Sabe-se que áreas de tecido cicatrizado exibem regiões de baixa condução que favorecem circuitos de reentrada e predispõem à taquicardia ventricular. No entanto, o mecanismo subjacente que conduz à fibrilação ventricular é menos claro. A instabilidade elétrica é raramente uma consequência de uma única anormalidade, e sim um processo dinâmico que envolve uma série de fatores que, em conjunto, conduzem a um evento fatal. Consequentemente, novos métodos incorporando diferentes modalidades são necessários para caracterizar a instabilidade elétrica ventricular. O presente estudo encoraja o desenvolvimento de estudos maiores que avaliem prospectivamente o uso de ECG para o rastreio de cicatriz miocárdica e consequente avaliação de risco de arritmia ventricular.O estudo de Erturk et al., 2 Myocardial scar, detected by contrast enhanced magnetic resonance imaging (ce-MRI), has been shown to be a predictor of prognosis and sudden cardiac death in patients with HFrEF.6 Cardiac MRI has emerged as a non-invasive gold standard for the assessment of scar and risk prediction of ventricular arrhythmias.8 Nevertheless, cardiac MRI can be time consuming, expensive, and not easily available.Myocardial fibrosis is a final common feature of most inflammatory pathway and is frequently seen in patients with heart failure with reduced ejection fraction (HFrEF).9 Ventricular repolarization is a complex electrical phenomenon which in clinical practice is measured from the beginning of the QRS complex to the end of the T-wave.10 Cardiac structural and electrical changes may cause action potential abnormalities, affecting the refractory period and thus favoring the onset of ventricular arrhythmias.10The 12-lead surface electrocardiogram (ECG) is a simple and inexpensive diagnostic tool that is widely used in clinical practice for the diagnosis of cardiac arrhythmias. The ECG waveform is the expression of the transmembrane action potentials and is composed of two distinct processes: depolarization and repolarization.Arquivos Brasileiros de Cardiologia , Erturk et al.11 conducted an observational, retrospective study evaluating the relationship between myocardial scar by ce-MRI and several electrocardiographic parameters of ventricular repolarization in patients with HFrEF. The authors observed prolonged measurements of QTc interval, Tp-e interval, and frontal QRS-T angle in patients with HFrEF who exhibited myocardial scar on ceMRI compared to those who did not.In this issue of the 11Based on multivariable analysis, Tp-e interval was the best parameter to predict the presence of myocardial scar. The authors concluded that it is possible to predict myocardial scar in HFrEF using ECG parameters.12 which determines the QT interval. Previous studies have shown a strong association between the presence of subendocardial scar and the abnormal ventricular repolarization in patients with coronary artery disease.13 Interestingly, community-based cardiac MRI studies have also demonstrated that the presence of subclinical scar detected by ceMRI was associated with increased mortality.14 Therefore, abnormal ventricular repolarization detected by ECG may be useful in predicting subclinical myocardial scar and identifying high risk patients.There are limited reports concerning the relationship between the presence of myocardial scar and changes in the ECG. In experimental models, the induction of subendocardial scar formation has been shown to prolong repolarization time of the M cells,15 it has several limitations, including the small sample size, single-center patient selection and the retrospective and observational design. Large prospective studies are needed to validate the ventricular repolarization parameters proposed here. The investigators established a solid basis of information that will move forward the electrocardiography field in future studies.Although the study presents encouraging results that add important information to prior reports,11 also highlights the intimate relationship between myocardial fibrosis and disturbances in electrical conduction. There has been a substantial effort in understanding scar composition and related electrical instability.7 It is well known that areas of scarred tissue exhibit regions of slow conduction that favor reentry circuits and predispose to ventricular tachycardia. However, the underlying mechanism that yield ventricular fibrillation is less clear. Electrical instability is rarely the consequence of a single abnormality but rather a dynamic process involving of a group of factors that together lead to a fatal event. Consequently, new methods incorporating different modalities are needed to characterize ventricular electrical instability. The current study motivates the development of larger, prospective study to evaluate the use of ECG for screening of myocardial scar and consequent evaluation of ventricular arrhythmia risk.This study, Erturk et al.