Objective: Ejection fraction preserved heart failure (HFpEF) is a common clinical syndrome with a high morbidity, accounting for ~50% of all heart failure patients, and a mortality comparable to that of ejection fraction reduced heart failure (HFrEF). The relationship between liver stiffness (LS) and HFpEF remains unclear. The purpose of this study was to explore the correlation between LS and the severity of HFpEF.Methods: We performed a prospective observational study. After accepting liver transient elastography on admission, consecutive 150 hospitalized HFpEF patients were divided into three groups based on their liver elasticity value: first-third quartiles. Left ventricular diastolic function, left ventricular hypertrophy degree, right cardiac function and short-term prognosis (≤1 year) were compared among the three groups, and the correlation between liver elasticity and each indicator was analyzed.Results: The elasticity of the liver was abnormally high in more than two-thirds of cases. The proportion of NYHA class III-IV in the third quartile group was significantly higher than that in the first quartile group . Significant differences were discovered in the level of lgNT-proBNP between the three groups . In terms of diastolic function and left ventricular hypertrophy, the ventricular septal e′ , lateral wall e′ , mean E/e′ , left atrial volume index , tricuspid regurgitation (TR) peak flow rate , left ventricular mass index (LVMI) in male  and in female  was significantly different between the third quartile and the first quartile. The proportion of patients with diastolic dysfunction in the third quartile was significantly higher than that in the first quartile . In terms of right cardiac function, right ventricular fractional area change (RVFAC) , tricuspid annular plane systolic excursion (TAPSE) , pulmonary systolic pressure , TR peak flow rate , and inferior vena cava diameter  were significantly different between the third quartile and the first quartile. More than half of HFpEF patients were combined with right ventricular dysfunction (RVD). Compared to HFpEF without RVD, HFpEF with RVD had higher male sex , higher NYHA class , higher proportion of atrial fibrillation , and higher liver elasticity value . In terms of short-term prognosis, the incidence of adverse cardiovascular events was significantly higher in the third quartile than in the first quartile (P = 0.003) and the second quartile (P = 0.008). Multivariate Cox proportional hazard analysis showed that adverse cardiovascular events were independently associated with NYHA class, atrial fibrillation, lgNT-proBNP and liver elasticity value .Conclusion: Increase of liver stiffness is common in HFpEF patients. Increased LS in HFpEF patients was significantly associated with worsen left diastolic function, left ventricular hypertrophy, and the right cardiac function. LS in HFpEF patients may be more than the result of right ventricular dysfunction. Male, atrial fibrillation, poorer NYHA class and increased liver elasticity value were significantly associated with HFpEF combined with RVD. Atrial fibrillation, poorer NYHA class, higher NT-proBNP, and increased liver elasticity value were independent predictors of poor short-term prognosis of HFpEF patients. Heart failure preserved ejection fraction (HFpEF) is a specific type of heart failure with a normal left ventricular ejection fraction (LVEF), which is characterized by abnormal diastolic function, decreased compliance, and increased stiffness . HFpEF iHeart failure, as a systemic disease, is often accompanied by impaired functional reserve of multiple organs, such as lung, blood vessels, skeletal muscle, kidney and liver , 5. ManyInflammation plays an important role in the pathophysiological process of HFpEF . HFpEF iIn the preliminary experiment, 30 HFrEF and 30 HFpEF patients were matched by sex and age 1:1 for liver elastography measurement  have typical signs or symptoms of heart failure; (2) LVEF ≥ 50%; (3) B-type natriuretic peptide (BNP) > 35 ng/L and/or N-terminal B-type natriuretic peptide precursor (NT-proBNP) > 125 ng/L. In addition, they met at least one of the following criterias: (1) evidence of left ventricular hypertrophy and/or left atrial enlargement, and (2) evidence of abnormal diastolic function. Exclusion criteria were as follows: (1) patients with acute heart failure, acute myocardial infarction, acute myocarditis, pericardial disease, and congenital heart disease; (2) patients with clear liver diseases, including various hepatitis and various cirrhosis with definite etiology ; (3) patients with advanced tumor; (4) patients requiring dialysis.n = 50), second quartile  and third quartile .Blood samples and echocardiography were obtained at admission . In addition, all patients accepted liver elastography at admission. The patients were divided into three groups according to the measured liver elasticity value (Elastic PQ) by the trinity method: first quartile  to calculate the left ventricular end-diastolic volume (Vd) and end-systolic volume (Vs), respectively. LVEF was then calculated by the formula LVEF = (Vd – Vs)/LVEF is calculated by Teichholz method: left ventricular end-diastolic dimension (LVDd) and left ventricular end-systolic dimension (LVDs) were measured during the cardiac cycle. Then, use the corrected cubic formula V = (2.4 + D)In this study, the liver elasticity value measured by transient elastography (TE) was used as the indicator to evaluate LS. LS measurements were performed by a single experienced examiner (Xu. MZ) at admission, who was blinded to all clinical data, using an ultrasonic elastography machine . In particular, TE is performed on a patient lying supine, with the right arm elevated to facilitate access to the right liver. The tip of the probe is in contact with the intercostal skin through a coupling gel in the 9th to 11th intercostal space at the level where TE would be performed. The operator, assisted by a time-motion image, locates a liver portion at least 6 cm deep and free of large vascular structures. The operator then presses the probe button to start the measurements (“shots”). TE measures the liver stiffness in a volume that approximates a cylinder 1 cm wide and 4 cm long, between 25 and 65 mm below the skin surface . The sofTE is a patient-friendly procedure: it only requires a short time (5 min) and can be performed bedside. The results are expressed in kilopascals (kPa), ranging from 2.5 to 75 kPa, and are available immediately. After recording 10 measurements, the average value is taken as the final measurement result.2, tricuspid regurgitation (TR) peak flow rate > 2.8 m/s. Therefore, ventricular septum e′, lateral wall e′, mean E/e′, left atrial volume index, and TR peak flow rate were used as indicators to evaluate left ventricular diastolic function in our study. All the above data were obtained by echocardiography. Then, according to the algorithm of left ventricular diastolic dysfunction in patients with normal LVEF developed by the guidelines writing group, the patients were judged for diastolic dysfunction  or 95 g/m2  is considered to have significant left ventricular hypertrophy. LVMI can be calculated from cardiac data and body surface area: LVM = (IVST + LVDd + PWT) 3-LVDd3; LVMI = LVM/BSA  (According to “Chinese Guidelines for the Diagnosis and Treatment of Heart Failure 2018” (ce area) .Up to now there is no uniform indicators for the evaluation of right cardiac function. In this study, we used the following indicators recommended by the Heart Failure Association of the European Society of Cardiology  to evaluShort-term prognosis is reflected by major adverse cardiovascular event (MACE) in 1 year after discharge, including cardiovascular death, malignant arrhythmia, myocardial infarction, stroke and re-hospitalization due to heart failure.n, %). Chi-square test was used to compare the counting data. If the frequency is <5, Fisher's exact-test is used. Spearman correlation analysis was used to analyze the correlation between liver elasticity value and diastolic function indicators, left ventricular remolding indicators and right cardiac function indicators. Statistics were conducted using SPSS 24.0. P < 0.05 was considered statistically significant.The measurement data were tested for normality and homogeneity of variance. measurement data obeying normal distribution and homogeneous population variance are presented with mean ± standard deviation, otherwise, logarithmic conversion was carried out and expressed in the form of lg (such as NT-proBNP). Since this study was a comparison among three groups, one-way analysis of variance and Kruscal-Wallis H test were used to compare the measurement data between groups according to whether they were in line with normal distribution and homogeneity of variance. For counting data, it is expressed as frequency and percentage , we take the logarithm of the NT-proBNP and then compare it between groups. As a result, the third quartile group had the highest lgNT-proBNP, as well as levels of abumin/globulin ratio (A/G), total bilirubin, direct bilirubin and indirect bilirubin. In contrast, ALT, AST, alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lipid levels and the electrolyte did not differ significantly among the three groups.In terms of laboratory data, as the overall value of NT-proBNP does not meet the normal distribution , total bilirubin , direct bilirubin , indirect bilirubin , ALP , GGT , and lgNT-proBNP  were significantly correlated. Scatter distribution of liver elasticity values and various parameters is shown in Spearman correlation analysis was performed between liver elasticity value and laboratory data. The results showed that the ratio of liver elasticity value to blood A/G . The higher the liver elasticity value, the higher the mean E/e′, and there were statistical differences between groups . The LAVI of the first, second and third quartile groups showed an increasing trend. There was a statistical difference between the first quartile group and the third quartile group (P = 0.008), as well as between the second quartile group and the third quartile group (P = 0.044). The higher the liver elasticity value, the higher the TR peak flow rate, and there was significant difference among all groups  . The comparison of the above data is shown in Ventricular septum e′, lateral wall e′, mean E/e′, left atrial volume index (LAVI), TR peak flow rate and left ventricular mass index (LVMI) were compared among the three groups. As a result, ventricular septum e′ and lateral wall e′ were lower in the third quartile than in the first quartile (< 0.001) . The LVMSpearman correlation analysis was performed between liver elasticity values and left ventricular diastolic function indicators and left ventricular hypertrophy indicators. The results showed that liver elasticity value was negatively correlated with ventricular septum e′ and lateral wall e′, but positively correlated with mean E/e′, LAVI, TR peak flow rate and LVMI . ScatterP = 0.008). On the contrary, proportion of patients with diastolic dysfunction in the third quartile was significantly higher than that in the first quartile . In addition, indicators of right heart volume/pressure, including pulmonary systolic pressure, TR peak flow rate and inferior vena cava (IVC) diameter all showed inter-group differences. Specifically, the pulmonary systolic pressure of the third quartile was significantly higher than that of the first and second quartile . TR peak flow rate differed significantly among all groups. The higher the liver elasticity value was, the greater the TR peak flow rate was . The higher the liver elasticity value was, the larger the IVC diameter was, and the IVC diameter in the third quartile was significantly greater than that in the first quartile . In addition, proportion of male, NYHA class, and proportion of atrial fibrillation in the RVD group were significantly higher than those in the no-RVD group .According to the cardiac ultrasound criteria for right heart dysfunction (RVD) of HFpEF established by the Heart Failure Association of the European Society of Cardiology, RVD exists when any of the following criteria is satisfied: RVFAC < 35%, TAPSE < 17 mm, TR peak flow rate > 2.8 m/s, IVC diameter > 21 mm, IVC collapse index < 50% at the end of inspiration. According to this criterion, 84 of the 150 patients in this study were combined with RVD, while the others were not. The liver elasticity value and basic data of the two groups were compared . As a reN < 5 in group), the chi-square test was not performed for these outcomes. However, significant differences were detected in the incidence of hospitalization due to heart failure and total number of major cardiovascular events (MACE) among groups . Total number of MACE in the third quartile was significantly higher in the third quartile than that in the first  and second quartile .All the patients were followed up, with a maximum of 386 days, a minimum of 52 days, and a median of 197 days. There was no statistical difference in the median follow-up time among the three groups. Due to the low incidence of cardiogenic death, malignant arrhythmia, acute myocardial infarction and stroke  and the second quartile . There was no statistical difference between the first quartile and the second quartile (detailed data seen in MACE-free Kaplan Meier (K-M) survival curves were drawn for the three groups, and the difference of the survival curves among groups were compared using the Log-Rank Test . As a reP < 0.0001). In the Multivariate analysis, increased LEV was independently associated with MACEs after adjusting for NYHA class, atrial fibrillation and lgNT-proBNP  of the patients had significant increased LS (liver elasticity > 7.0 kPa). This is an interesting finding, which indicates that increased LS in HFpEF is not entirely the result of RVD, on the contrary, as said before, is likely to be the joint action of inflammation, oxidative stress and vascular endothelial cell damage factors. This once again proved HFpEF is a systematic disease, and increased liver stiffness and myocardial stiffness may be the result of common factors acting on different organs.Although woman is a risk factor for HFpEF, we found a significantly higher proportion of men in HFpEF combined with RVD than in HFpEF without RVD. Previous studies in HFrEF reported an association between males and right ventricular dysfunction , 39. RV This study further explored the correlation between LS and short-term prognosis in patients with HFpEF. With the increase of LS, the prognosis of patients with HFpEF became worse, which was mainly manifested by an increase in the number of re-hospitalizations due to heart failure. MACE-free Kaplan Meier (K-M) survival curves showed that with the increase of follow-up days, the survival rate without MACE in the third quartile was significantly lower than that in the first and the second quartile. Multivariate Cox risk analysis showed that liver elasticity value, NYHA class, atrial fibrillation, and lgNT-proBNP were independently associated with poor prognosis of HFpEF. Our results prove that the degree of LS is closely related to the short-term prognosis of patients with HFpEF, and the more severe the degree of LS, the worse the short-term prognosis. More importantly, this study provides a theoretical support for this correlation, namely that the degree of LS reflects left ventricular diastolic function, left ventricular hypertrophy, and right cardiac function in patients with HFpEF. In other words, the degree of LS can predict the severity of HFpEF, and thus predict its clinical outcome. In terms of the predictive value of prognosis, liver elasticity value is better than NT-proBNP in some aspects. For example, NT-proBNP reflects the immediate severity of heart failure, vulnerable to cardiac functional state and change greatly. In contrast, as an indicator of liver stiffness, liver elasticity value is the result of long-term heart-liver influence, so it is more stable and can better reflect the long-term cardiac function status of patients. Therefore, liver elasticity value as a prognostic index has a certain promotion value.There are some limitations in this study. First, assessments of diastolic function, ventricular hypertrophy, and right cardiac function were based on echocardiographic indicators, lacking hemodynamic indicators such as cardiac MRI and invasive catheter measurements. Secondly, the poor prognosis in this study mainly refers to the number of re-hospitalizations due to heart failure rather than death. Due to the limitation of follow-up time and sample size, we could not clearly establish the correlation between LS and mortality.Increased LS is common in patients with HFpEF. The degree of LS reflected by liver elastography is not associated with LVEF, but closely correlated with left ventricular diastolic function, left ventricular hypertrophy, and right cardiac function in patients with HFpEF. Male, atrial fibrillation, higher NYHA class, and higher liver elasticity value are independently associated with RVD in HFpEF. Moreover, Increased LS is associated with worse short-term (<1 year) prognosis for HFpEF. Future studies with larger sample sizes, longer follow-up, and the introduction of cardiac MR and invasive cardiac catheterization are warranted to further explore the association between LS and HFpEF.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee of Suzhou Dushu Lake Hospital. The patients/participants provided their written informed consent to participate in this study.JZ designed the study and collected case data. MX analyzed the data and wrote the article. TC and YZ gave guidance to the development of this study and the writing of the article. All authors contributed to the article and approved the submitted version.This work was supported by grants from National Natural Science Foundation of China (Nos. 81873486 and 81770327), Natural Scientific Fund of Jiangsu province (No. BK20161226), Jiangsu Province's Key Provincial Talents Program (No. ZDRCA2016043), Jiangsu Province's 333 High-Level Talents Project (No. BRA2017539), and Jiangsu Provincial Medical Innovation Team (No. CXTDA2017009). The funders had no roles in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Mid-diastolic events (L events) include three phenomena appreciable on echocardiography occurring during diastasis: mid-diastolic transmitral flow velocity (L wave), mid-diastolic mitral valve motion (L motion), and mid-diastolic mitral annular velocity (L’ wave). L wave is a known marker of advanced diastolic dysfunction in different pathological clinical settings such as left ventricle and atrial remodeling, overloaded states, and cardiomyopathies. Patients with L events have poor outcomes with a higher risk of developing heart failure symptoms and arrhythmic complications, including sudden cardiac death. The exact mechanism underlying the genesis of mid-diastolic events is not fully understood, just as the significance of these events in healthy young people or their presence at the tricuspid valve level. We also report an explicative case of a patient with L events studied using speckle tracking imaging of the left atrium and ventricle at the same reference heartbeat supporting the hypothesis of a post-early diastolic relaxation or a “two-step” ventricular relaxation for L wave genesis. Our paper seeks to extend knowledge about the pathophysiological mechanisms on mid-diastolic events and summarizes the current knowledge. Recently, echocardiography and other diagnostic techniques in the field of cardiovascular diseases have been equipped with new application tools ,5,6,7,8.The studied populations were heterogeneous, mostly composed of aged patients having different underlying cardiovascular disease (CVD) with no significant valvular heart disease (VHD) . Althougp < 0.001) [Since well-represented diastasis is a fundamental prerequisite, L events are associated in clinical scenarios with a low HR and the prevalence seems higher in patients with atrial fibrillation (AF). Ha et al. reported a prevalence of triphasic transmitral flow of 0.9% in a sample of 9004 subjects in SR who underwent echocardiography examination in a time interval of 9 months . A subse< 0.001) . In thisRegardless of the basal rhythm, two groups of patients reach the highest rate of prevalence of L events: left ventricle hypertrophy (LVH), including hypertrophic cardiomyopathy (HCM), and heart failure (HF) patients. In 2008, Lam et al. reported in a population of subjects in SR with LVH and preserved left ventricular ejection fraction (LVEF) a prevalence of triphasic transmitral flow and mid-diastolic mitral annular velocity (L’ wave) patterns of 20% and 30%, respectively . RecentlIn partial discordance with previous studies, Kim et al. noted a triphasic transmitral flow pattern in only 1% of an entire population of 20,845 subjects with SR and any degree of diastolic dysfunction . The autThe relationship with HF is bidirectional since patients with an L wave (in both AF or SR) more frequently had HF (and were at risk of developing HF-related symptoms) and the HF subjects more frequently expressed a triphasic transmitral pattern. A high prevalence of the L wave was reported in both groups of patients with preserved and reduced LVEF (36% of heart failure cases with preserved ejection fraction (HFpEF) and 28% of heart failure cases with reduced ejection fraction (HFrEF)) during SR . In a prThere are no epidemiologic data about L events in young healthy people so prevalence in this group remains unknown.Normally, atrial function can be summarized as follows: reservoir, conduit, and contractile ,24,25,26During AF, the atria lack active contraction so they have to work at a higher pressure to fill the ventricles adequately, the conduit phase lengthens, and L events are more likely to take place.In 1986, Keren et al. studied the relationship between L events and other diastolic events . They stContrary to the model of Karen et al., Hatle et al. speculated that delayed left ventricular relaxation could contribute to L wave genesis . AccordiIn normal individuals, the diastole is initiated by the relaxation of the ventricle through a “ventricular suction mechanism”, thus the E’ wave occurs simultaneously or slightly before the E wave. In case of advanced (diastolic dysfunction) DD, high atrial pressure causes the opening of the mitral leaflets when the ventricle has not yet begun to relax, thus the E wave anticipates the E’ wave . In thisDuring diastasis, the LV exhibited global mid-diastolic events appreciable in the velocity and strain rate curves  while thThe literature offers other physiopathological mechanisms of L events as well.The early diastolic phase was described as composed of two moments, the first due to longitudinal relaxation producing a laminar diastolic flow toward the apex and the second due to radial expansion, creating a convective vortex decelerating the flow. The latter phase is responsible for the descending arm of transmitral early flow velocity (E wave) and may be involved in or affect L events . Ghosh eThere is a paucity of data on tricuspid L events. We found a report of a young patient with previously treated congenital heart disease who presented with acute clinical signs of peripheral congestion. In addition to high pulmonary pressure, a triphasic transtricuspid pattern and the tricuspid L’ wave were related with the same ventricular alterations connected with the appearance of L events on the left side of the heart: hypertrophic ventricle and diastolic dysfunction . NotablyIn summary, there appears to be a different mechanism generating L events in healthy versus pathologic hearts.L events characterize abnormal heart properties (particularly LVH) and functions both in SR and AF patients. L wave is a marker of poor prognosis and advanced diastolic dysfunction.Sinus rhythm allows for easier and more rapid interpretation of mid-diastolic events. Lam et al investigated the prognostic role of L events in two studies using 177 recruited patients with LVH and preserved LVEF ,20. L wap = 0.0012). The amplitude (p = 0.0002) and the time velocity integral (TVI) of the L wave were significantly greater in the patients with the L’ wave (p = 0.0079), but the meaning of this remains elusive. The authors utilized the Valsalva maneuver performed in all but two patients and an impaired relaxation pattern was unmasked in 85% of the cases, but no information about L’ wave variations during maneuvers was reported. In partial disagreement with what was previously reported, a prospective study for long-term prognosis involving 144 subjects with a triphasic transmitral pattern reported that the septal L’ wave  was more prevalent in the cohort of patients who experienced cardiac events; however, this did not reach statistical significance for predicting clinical outcomes (p = 0.059). A particularly poor prognosis was reported among the patients with altered NP, dilated LA, and a triphasic transmitral pattern [Consistent with the previous study, Ha et al. reported that the L’ wave in addition to the L wave indicated a more advanced diastolic dysfunction . They stp < 0.01; p < 0.05 for all-cause mortality in HFpEF). In both groups (HFrEF and HFpEF), the presence of the L wave was connected to grade II and III of diastolic dysfunction as well as to major anatomical alteration ). The provocative maneuvers  performed on HFpEF patients evoked the appearance of an L wave suggesting their diastolic equilibrium could be easily unbalanced. Regarding this, in our experience, we observed several cases of L wave and L’ wave appearance after extrasystolic beats  in decompensated patients without any baseline L events. A post-extrasystolic beat increases venous return and could be a surrogate of the provocative maneuvers providing similar information.The prognostic role of the L wave in HF patients was explored by Masai et al. in 2017 . The stuThe common final pathway of advanced diastolic dysfunction is the increased LV filling pressure with pulmonary vascular congestion so the aim of diastolic evaluation is to know if the filling pressure is above normal. The connection between L events and increased filling pressure was mostly based on indirect markers, E/E’ ratio, while invasive measurement often failed to demonstrate a significant correlation ,37,38.p = 0.015). Although with a limited sample size, this was one of the few studies that correlated invasive data with L events. The L’ wave was present in over a quarter of the total population (and in the majority of the patients with the L wave) but without reaching any clinically relevant association. This was also reported in almost half of the healthy volunteers and in this case the authors presumed a different mechanism producing the L’ pattern in healthy versus HF patients [In a publication involving 48 patients affected by dilated cardiomyopathy undergoing catheterization for heart transplantation candidacy, the mean pulmonary capillary wedge pressure (PCWP) was significantly higher in the cohort expressing an L wave . The L wave was associated with significant major cardiac morphologic alterations such as LVH , echocardiographic markers of increased left atrial pressure such as E/e’ ratio >15 , as well as higher levels of NP measured together with echocardiograms. No significant correlation was reported between the amplitude of the L wave and the E/e’ ratio or the left atrium volume so the mere identification of the L wave informed about advanced diastolic dysfunction and poor prognosis. Subsequently, consistent results on the prognostic value of the L wave in a similar population of AF patients were reported [p = 0.016) and all-cause mortality . The authors also demonstrated that added to conventional clinical and echocardiographic parameters, the L wave can provide incremental prognostic value for adverse cardiac events (p = 0.048) and all-cause mortality (p = 0.002).Nakai et al. studied the prognostic impact of the L wave on 99 persistent AF patients during a mean follow-up of 5.7 months . The evereported . The patp < 0.003) and a lower mean ventricular response compared to the other. Consistent with previous studies, the L wave-positive group had significantly greater morphologic cardiac alterations (LA volume and LV mass) and more severe diastolic alteration, as exemplified by the E/e’ ratio or the E/Vp ratio (p < 0.001). After achieving SR, the recurrence rate of AF at 30 days was 45% in the L wave-positive group, and the L wave was an independent predictor of early arrhythmia recurrence . The control echocardiograms in SR at 24 h after successful ECV showed differences in diastolic parameters but the presence of the L wave was no longer present. It would have been interesting to know how many patients still presented an L wave in SR. This leads us to the question: “Can the evidence of an L wave have prognostic implications even if it only appears in specific circumstances ?” This assertion seems likely. Another question is if the L wave appearance during provocative maneuvers in an L wave-“naïve” patient would have long-term prognostic implications.The natural history of AF contemplates an early stage of paroxysmal episodes that evolve later in the stable stage of persistent AF. This evolution involves structural changes of LA, which appears dilated, fibrotic, and dysfunctional. Recurrence of AF after spontaneous or iatrogenic cardioversion is a frequent problem and can cause episodes of syncope, acute HF, and thromboembolism. Left atrial dimensions, LVH grade, and advanced diastolic dysfunction are well-known risk factors of AF recurrence after electrical cardioversion . Ari et Some interesting single experiences reported the transient appearance of the L wave in different pathologic conditions of volume overload, such as severe anemia, new-onset HF (with or without new-onset AF), acute VHD, or acute coronary syndrome (ACS) ,41.Morisawa et al. described an interesting case of a pacemaker (PM)-dependent patient (pacing mode DDD) developing acute HF and new-onset AF . In thesInterestingly, another report described by Misumi et al. reported the appearance of an L wave in a patient developing acute severe mitral regurgitation, cardiac decompensation, and a transient episode of AF . After sp = 0.28 and p = 0.14, respectively). According to this, the L wave could represent a prognostic modifying factor and a complex index related to different variables rather than a diagnostic parameter of diastolic dysfunction.A common limitation of all the cited studies was the absence of invasive data. In this regard, Kaitka et al. retrospectively enrolled 48 subjects of the CHATARSIS trial. Twenty-four were in SR, 24—in AF . They unBased on the available data, patients with AF and diastolic dysfunction presenting an L wave have an increased risk of HF, all-cause mortality, and early recurrence of arrhythmia after a rhythm control strategy. Other investigations in larger cohorts are needed to corroborate these data.An abnormal diastolic function is an important determinant of HF in HCM, and AF paroxysms frequently exacerbate symptoms. Noninvasive evaluation of diastolic dysfunction in these patients is complex and less accurate . As mentp < 0.001) and for baseline factors  [In a recent publication by Saito et al., patients with an L wave had adverse midterm prognosis (mean follow-up of 8.8 years) with significantly higher HCM-related death. The L wave was independently associated with HCM-related death in a multivariable analysis using two different models adjusting for conventional SCD risk factors  . L wave p = 0.002), and the L wave was independently related to cardiac events (p = 0.03). The receiver operating characteristic (ROC) analysis defined 0.2 m/s as the L wave score cutoff value for cardiac events . Consistently with previous data, the SCD rate in this cohort was 0.46% per year [The role of the L wave in HCM patients with low HCM risk–SCD score and good functional status  was studper year .We found a single publication about the presence of an isolated septal L’ wave in an HCM patient with previous septal myectomy and a restrictive triphasic transmitral pattern . The conGiven the relatively high prevalence in this cohort of subjects, the L wave as other new parameters from other techniques  could be used for identifying a subgroup of patients with increased risk of cardiac events, particularly in the low SCD risk score group .The L wave is by far the most studied mid-diastolic phenomenon. It can define a category of patients at a particularly increased risk of HF and all-cause mortality, particularly when it is combined with altered NP levels. It could also be considered as a modifying risk factor for SCD in HCM patients. L events should be investigated during routine examinations as it is relatively easy to perform and has prognostic implications in different clinical scenarios.With the exception of young healthy patients, observation of L events is expected in 1–30% of cases based on the individual’s features. The classic patient for L events is a bradycardic elderly female with multiple CV risk factors with marked LVH and grade II–III diastolic dysfunction.The genesis of L events should be found in the complex atrioventricular interactions. The evaluation of the longitudinal component of diastolic ventricular relaxation with TDI leads to mid-diastolic flow as a consequence of marked delayed ventricular relaxation. In our report, we examined the temporal relationship between transmitral flow and chamber diastolic events. We noted an inverted time of early diastolic events, compatible with a high atrial pressure, followed by synchronous mid-diastolic events, supporting the idea of a “two-step ventricular relaxation” for the genesis of the L wave. The LA curves obtained by STI showed no significant variations during diastasis suggesting a minor role for the LA.The association of L events with certain anatomical features or changes in loading conditions is consistent with more than one theory and the acceptance of one does not strictly exclude the other so it appears there is a different mechanism generating L events in healthy versus pathological hearts.In the acute context, such as acute VHD or ACS, sudden and reversible appearance of L events is mainly related to an abrupt elevation of filling pressure. Therefore, in decompensated patients, the evidence of an L wave could contribute to the assessment of loading conditions and response to diuretic treatment.Mid-diastolic mitral annular motion is frequent in healthy subjects without clear meaning, especially if not accompanied by a triphasic transmitral pattern, but could represent a diastolic alteration preceding the appearance of an L wave.Further studies including L events in prognostic risk scores in specific subsets of patients are warranted to assess their clinical significance.


Long-term survivors of Hodgkin lymphoma (HL) and mediastinal non-Hodgkin lymphoma experience late adverse effects of radiotherapy and/or anthracycline-containing chemotherapy, leading to premature cardiovascular morbidity and mortality.The aim of this study was to identify markers for subclinical cardiovascular disease using cardiovascular magnetic resonance (CMR) in survivors of HL and non-Hodgkin lymphoma.CMR was performed in 80 lymphoma survivors treated with mediastinal radiotherapy with or without anthracyclines, and results were compared with those among 40 healthy control subjects matched for age and sex.P < 0.001) and LV mass  and higher LV end-systolic volume  were found in lymphoma survivors. LV global strain parameters were also significantly worse in lymphoma survivors . Native myocardial T1 was significantly higher in lymphoma survivors compared with healthy control subjects , and late gadolinium enhancement was present in 11% of the survivors.Of the 80 lymphoma survivors, 98% had histories of HL, the mean age was 47 ± 11 years, and 54% were male. Median radiotherapy dose was 36 Gy (interquartile range: 36-40 Gy), and radiotherapy was combined with anthracyclines in 70 lymphoma survivors (88%). Mean time between diagnosis and CMR was 20 ± 8 years. Significantly lower left ventricular (LV) ejection fraction (53% ± 5% vs 60% ± 5%; Long-term lymphoma survivors have detectable changes in LV function and native myocardial T1 on CMR. Further longitudinal studies are needed to assess the implication of these changes in relation to treatment and clinical outcome.  In recent decades, improvements in the treatment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) have resulted in an increased survival rate of approximately 80% to 90%. Nevertheless, long-term survivors may experience several late adverse effects that may lead to premature morbidity and mortality , 2, 3. CNL7958). This study was approved by the Institutional Review Board, and written informed consent was obtained from all patients and healthy control subjects (MEC17-505/MEC-2014-096).For this single-center cross-sectional study, we screened lymphoma survivors of the BETER  outpatient clinic of the Erasmus Medical Center between February 2018 and October 2020 . LymphomStandard 12-lead electrocardiography was performed at rest and was scored for heart rate, rhythm, conduction times, T-wave amplitude, and ST-segment deviations. In case of prolongation of the QRS complex (>120 ms), the type of bundle branch block was noted.Transthoracic echocardiography was performed on a Philips Epiq 7C using a standardized acquisition protocol, and parameters related to diastolic function and valvular disease were measured. LV diastolic function was defined as normal, grade I , grade II , grade III (restrictive filling), or unclear on the basis of Doppler mitral inflow pattern parameters, including early (E) and late (A) LV filling velocities, E/A ratio, and tissue Doppler imaging–derived septal early diastolic velocities (e′) . ValvulaElectrocardiography and transthoracic echocardiography were not performed in healthy control subjects.CMR examinations were performed on a SIGNA Artist 1.5-T scanner  with a dedicated anterior-array coil, electrocardiographic gating, and breath-hold techniques. The detailed scan protocol and scan parameters are described in the Steady-state free precession cine images were obtained during breath-hold in all long-axis views  and in a contiguous short-axis stack, with coverage from base to apex. LV and right ventricular dimensions, systolic function, and LV mass were determined on the short-axis images. Volumes and mass were corrected for body surface area.Strain analyses using 2-dimensional feature tracking CMR were performed. Myocardial LV global longitudinal strain (GLS) was measured using all long-axis views. Endocardial right ventricular GLS was measured in the 4-chamber view. Myocardial global circumferential strain (GCS) and myocardial global radial strain measurements were performed using a basal, midventricular, and apical short-axis view. In addition, systolic and diastolic hemodynamic forces were calculated per entire heartbeat.Images for T1 mapping were obtained in a midventricular short-axis slice, using a modified Look-Locker inverse recovery sequence with a 5(3)3 acquisition scheme pre-contrast and a 4(1)3(1)2 acquisition scheme post-contrast. The same slice location was used for T2 mapping. The whole myocardium in the midventricular slice was included. Only in the case of artifacts was part of the myocardium excluded. Motion correction was performed. A blood sample was collected immediately after CMR examination for the determination of hematocrit in order to calculate extracellular volume fraction. The cell volume was calculated using the following formula: LV mass (indexed)/1.05 × [1 − extracellular volume] . Phase-sDedicated software was used for these measurements .2, epirubicin ≥540 mg/m2, or mitoxantrone ≥90 mg/m2.Baseline was defined as the date of CMR. The collected patient data included general, cardiovascular, and oncologic data; physical examination; and laboratory values. In addition, lymphoma survivors were stratified according to: 1) total mediastinal radiotherapy dose ≤36 and >36 Gy (median); and 2) treatment with or without high-dose anthracyclines. High-dose anthracyclines were defined as doxorubicin ≥300 mg/mContinuous data were tested for normality before analysis using the Kolmogorov-Smirnov test and are expressed as mean ± SD or median (interquartile range), as appropriate. Categorical variables are presented as number (percentage).t-test or the Mann-Whitney U test depending on their distributions, and categorical data were compared using the Pearson chi-square test or the Fisher exact test, as appropriate.Baseline characteristics were compared between lymphoma survivors and healthy control subjects, with aspects of CVD described in survivors. Subsequently, survivors were stratified according to radiotherapy and anthracycline dose for the comparison of baseline, transthoracic echocardiographic, and CMR characteristics. Continuous variables were compared using Student’s P values <0.20 in the univariable linear regression were included in a multivariable analysis (multivariable model 1). A second model was performed adding the following variables irrespective of P value: duration between diagnosis and CMR and total dose of anthracycline chemotherapy (multivariable model 2). Results are presented as parameter estimated (β) and 95% CI. Multicollinearity was assessed using the variance inflation factor.Univariable and multivariable linear regression analyses were used to assess the associations of baseline and treatment variables with LV ejection fraction, GLS, GCS, and LV mass in lymphoma survivors. All variables with P values <0.05 were considered to indicate statistical significance. Statistical analyses were performed using SPSS version 25 (IBM).All analyses were 2-tailed, and A total of 80 consecutive HL (n = 78) and mediastinal NHL (n = 2) survivors and 40 healthy control subjects matched for age and sex on a group level were included in this study . BaselinMost lymphoma survivors had a history of stage II disease (74%), and mean age at diagnosis was 27 ± 9 years. All survivors had been treated with mediastinal radiotherapy, with a median prescribed total dose of 36 Gy (interquartile range: 36-40 Gy). This local treatment was combined with systemic anthracycline chemotherapy in 70 of the survivors (88%), of whom 12 (15%) received high-dose anthracyclines. A total of 11 lymphoma survivors (14%) experienced a relapse requiring additional radiotherapy and/or anthracycline chemotherapy. The mean interval between diagnosis and CMR was 20 ± 8 years. Cardiovascular risk factors and medication are described in P < 0.001) and LV mass  and higher LV end-systolic volume  were found in lymphoma survivors. Moreover, they showed significantly lower right ventricular volumes than healthy control subjects  (P = 0.328). GLS , GCS , and global radial strain  of the LV were reduced in lymphoma survivors. Furthermore, the lateral-to-septal hemodynamic force was significantly lower in survivors , while the apical-to-basal hemodynamic force was comparable between both groups (P = 0.58). No significant difference in right ventricular myocardial strain was found, in line with preserved right ventricular ejection fraction.Differences in CMR characteristics between lymphoma survivors and healthy control subjects are shown in for all) , while rP = 0.007) and cell volume fraction  were observed, with higher values in lymphoma survivors. LGE, other than at the hinge point location, was detected in 11% of survivors (median LGE quantification 3.0% [interquartile range: 1.9%-4.1%] of left ventricle). Subendocardial and transmural LGE patterns, most likely due to myocardial infarction, were present in 4 of the survivors (5%). Further evaluation by coronary computed tomographic angiography in 6 survivors revealed in 1 survivor a significant stenosis in an intermediate branch, consistent with an area of subendocardial LGE. In 11 survivors (14%), hinge-point LGE was found (median LGE quantification 1.7% [interquartile range: 1.0%-2.3%] of LV). LGE images are presented in Both groups were similar with respect to extracellular volume fraction and myocardial T2; however, statistically significant differences regarding myocardial T1  and diabetes  were found to be independent significant predictors of LV ejection fraction. Male sex , time between diagnosis and CMR , and diabetes mellitus  were associated with impaired GLS. For GCS, male sex  and body mass index  were found to be predictors. Male sex , body mass index , and total mediastinal radiotherapy dose  were associated with LV mass.Results of the univariable and multivariable analysis for predictors of LV ejection fraction and GLS are shown in P = 0.053). A similar result occurred with regard to the association between total mediastinal radiotherapy dose and LV mass. Adding anthracycline dose and time between diagnosis and CMR to the models for GLS and GCS did not change the results. As diabetes mellitus appeared to be a strong predictor of LV ejection fraction and LV mass, but only 3 lymphoma survivors with diabetes were included, a sensitivity analysis was performed excluding these 3 survivors. The results did not substantially change , the effect of total mediastinal radiotherapy dose for the association with LV ejection fraction was comparable with that in multivariable model 1 , although the result was no longer statistically significant  acute <14 days); 2) early (1 week to 1 year); and 3) late (average 7 years) after the initiation of treatment. Acute onset cardiotoxicity is characterized by arrhythmias, acute coronary syndrome, myocarditis, transient LV dysfunction including acute heart failure, and electrocardiographic abnormalities, which can be reversible. However, there may also be myocardial, valvular, or coronary endothelial injury that can eventually progress to early or late onset cardiotoxicity. This can be irreversible, with a poor prognosis The prevalence of electrocardiographic abnormalities in our study was low and in line with a previous study in long-term lymphoma survivors . HoweverAs is known from published research, LV mass may decline following anthracycline administration, with an inverse relationship between dose and LV mass ,18. The Small but significantly worse LV function and differences in volumes were found in lymphoma survivors. Only LV end-systolic volume was significantly higher in lymphoma survivors. This LV remodeling may develop because of myocardial damage from earlier treatment with radiotherapy and/or anthracyclines , 24, 25.Native myocardial T1 was significantly higher in lymphoma survivors compared with healthy control subjects. This may suggest that diffuse myocardial fibrosis is actually present in lymphoma survivors, but it may still be explained by partial volume effect due to decrease of the amount of myocardial tissue. Extracellular volume fraction, which is associated with native T1, was not increased in lymphoma survivors, although our control subjects also demonstrated higher than expected myocardial extracellular volume. However, research has shown that extracellular volume fraction has a lower discriminatory performance compared with native T1 . PreviouSubendocardial and transmural LGE was present in 5% of lymphoma survivors, which was most likely consistent with myocardial infarction. This can be a consequence of coronary artery disease due to treatment with radiotherapy. In 6% of the survivors, the LGE pattern was midmyocardial or epicardial. No differences were found in the presence and localization of LGE between higher and lower doses of radiotherapy and/or anthracyclines. LGE at the hinge points was also prevalent in our cohort, although this is not specific for late cardiotoxicity. Hinge-point LGE is rather common in the (older) general population but also in specific populations such as athletes, making it difficult to identify the cause of this nonischemic LGE pattern.Cardio-oncology is a relatively new field and still growing because of increased survival rates. More knowledge about subclinical CVD in long-term survivors of HL is needed for the implementation of preventive and/or therapeutic treatment in order to reduce its burden . TherefoFrom this study we can deduce that lymphoma survivors are not exempt from subclinical CVD in comparison with healthy control subjects. This manifests mainly in changes in LV function, mass, and native myocardial T1. CMR is a suitable imaging modality for the detection of these changes, mainly because of its unique ability of tissue characterization. To the best of our knowledge, only a few studies have been performed to detect subclinical CVD using CMR in this study population ,29. TherAlthough comprehensive CMR was performed, the sample size was relative small, with only 80 lymphoma survivors included. These survivors were compared with age- and sex-matched healthy control subjects. However, unmeasured confounding cannot be excluded. There is selection bias by including only less affected lymphoma survivors due to the exclusion of patients with previous surgical or percutaneous intervention for valvular or coronary artery disease. However, we still found evident signs of subclinical CVD, which underscores the severity of the problem in this relatively young study population. However, we acknowledge that we did not adjust for multiple testing, and as such our results are susceptible to type I error. Only 2 patients with NHL were included, and therefore no conclusion can be drawn regarding HL versus NHL. All consecutive patients fulfilling the inclusion criteria of the PROCARBI study were included, and the treatment of HL and mediastinal NHL is comparable, so we left these survivors in the analysis. In addition, stress perfusion CMR for the detection of ischemia was not performed, so in theory, asymptomatic coronary artery disease could have been missed. Finally, no conventional tests  were performed in healthy control subjects.PerspectivesCOMPETENCY IN MEDICAL KNOWLEDGE: Long-term survivors of HL and mediastinal NHL lymphomas experience late adverse effects of mediastinal radiotherapy and/or anthracyclines, which lead to premature cardiovascular morbidity and mortality. Markers of CVD on CMR can detect changes in LV myocardial function and native myocardial T1. Lymphoma survivors treated with mediastinal radiation therapy and 88% received anthracyclines, had lower LV ejection fraction and LV mass compared with control subjects. LV global strain parameters were also worse. Our multivariable analysis showed that total mediastinal radiotherapy dose was significantly associated with LV ejection fraction, while male sex and duration between diagnosis and CMR were significantly associated with worsened GLS. Regular cardiac evaluation with cardiac imaging should be considered in lymphoma survivors for the detection of subclinical CVD.TRANSLATIONAL OUTLOOK: Further longitudinal studies are needed to assess the implications of changes in LV function and native myocardial T1 in relation to clinical outcome.Lymphoma survivors are not exempt from CVD, which can be detected by changes in LV function and native myocardial T1 with CMR. Further longitudinal studies are needed to assess the implication of these changes in relation to clinical outcomes.The authors have reported that they have no relationships relevant to the contents of this paper to disclose.


In childhood cancer survivors (CCSs) anthracycline-related cardiotoxicity is an important cause of morbidity and late mortality, but the optimal modality of cardiac surveillance still remains to be defined. The aim of this study was to assess whether non-invasive echocardiography-based functional cardiac measures can detect early subclinical myocardial changes in long-term pediatric cancer survivors who received anthracycline therapy.2. All subjects underwent a comprehensive functional echocardiographic protocol study including two-dimensional echocardiography (2D Echo), tissue Doppler imaging (TDI), speckle tracking (STE) and three-dimensional echocardiography (3D Echo). Patients were studied at a mean follow-up time of 6.5 ± 2.8 years from the end of therapy.Twenty anthracycline-treated long-term CCSs and 20 age, sex, and body surface area matched healthy controls were enrolled in this study. Among cancer survivors, mean age at diagnosis was 6.5 ± 4.4 years, and the mean cumulative anthracycline dose was 234.5 ± 87.4 mg/mNo significant differences in two-dimensional left ventricle ejection fraction (LVEF), diastolic parameters and speckle tracking (STE)-derived myocardial strain were observed between patients treated with anthracyclines and controls. Myocardial performance index was significantly prolonged (p = 0.005) and three-dimensional LVEF was significantly reduced (p = 0.002) in CCSs compared to controls, even though most values were within the normal range. There were no significant correlations between 2D, STE, and 3D echocardiographic parameters and age at diagnosis or duration of follow-up. No significant differences in echocardiographic parameters were found when stratifying cancer patients according to established risk factors for anthracycline cardiomyopathy.This study found significantly reduced three-dimensional LVEF in CCSs compared with controls, despite no significant differences in two-dimensional LVEF and longitudinal strain values. These findings suggest that long-term CCSs who had received anthracycline therapy may be found to have subclinical features of myocardial dysfunction. However, further studies are needed to demonstrate the validity of new imaging techniques, including STE and 3D Echo, to identify patients at risk for cardiomyopathy in the long-term follow-up of CCSs. Advances in treatment strategies for childhood cancer have resulted in a significant improvement in survival , 2, but Left ventricle (LV) dysfunction and heart failure (HF) are the most concerning cardiovascular complications of cancer therapies and could increasingly become a main cause of morbidity and death of childhood cancer survivors s (CCSs) , 8.The early detection of cardiotoxicity is often challenging, due to a long subclinical phase of LV dysfunction; however, an early diagnosis of cardiovascular disease in these patients would be crucial as it could allow a timely initiation of cardioprotective therapies that might delay myocardial remodeling and prevent LV cardiomyopathy.Because of its widespread availability and safety, two-dimensional echocardiography (2D Echo) is standardly utilized in monitoring cancer patients, although it is not always adequate to detect an early, clinically asymptomatic stage of disease . RecentlThe aim of this study was to assess whether advanced non-invasive echocardiography-based methods can be helpful in detecting early subclinical myocardial dysfunction in childhood anthracycline-exposed cancer survivors.This is an observational case–control study investigating 20 CCSs who received anthracycline therapy compared with 20 healthy subjects matched according to age, sex, and body surface area.CCSs patients were followed at the Pediatric Oncology Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy and were evaluated between October 2019 and February 2020. All patients received anthracycline therapy by a central line, with anthracycline infusion lasting 4 h.2; no symptoms of HF and normal global LV systolic function [defined as a LV ejection fraction [LVEF] ≥55%, and a LV shortening fraction (LVSF) ≥28%] at the last standard echocardiogram. Exclusion criteria included a history of congenital cardiac defects or any other cardiac disease; mediastinal/chest radiotherapy; bone marrow or staminal cells transplantation; signs and/or symptoms of acute and early cardiotoxicity. Healthy subjects were children referred to our Pediatric Cardiology Unit for complaints such as chest pain or palpitation, who were found to have normal cardiac examination, electrocardiogram, and standard transthoracic Doppler echocardiography.Inclusion criteria for the study were: completion of anthracycline therapy for more than 3 years; cumulative anthracycline dose <360 mg/mPrior to the participation, the patients and their parents provided signed consent forms after being informed about the aim of the project as foreseen by the Italian Law on Privacy and the Safeguarding of the Sensitive Data . The study was carried out in accordance with the Helsinki declaration of human rights. Approval by the Ethics Committee was not necessary since echocardiography is recommended as the primary cardiomyopathy surveillance modality for assessment of left ventricular systolic function in follow-up of survivors treated with anthracyclines.2, renal failure), and modifiable cardiovascular risk factors  were collected from CCSs patients.Demographic characteristics, blood pressure (BP), heart rate (HR), body mass index (BMI), and body surface area (BSA) were collected from all subjects. Type of malignancies, age at diagnosis, time since the last anthracycline dose, cumulative anthracycline dose, non-modifiable risk factors , tissue Doppler imaging (TDI), speckle tracking (STE), and three-dimensional echocardiography (3D Echo).® ultrasound system with a Philips X5-1 probe . Standard imaging planes were acquired according to current guidelines and recording three beat loops saved in DICOM format and stored in a workstation. These digital loops were interpreted by the same physicians, together, and both were blind to the subject’s group.All echocardiographic studies were performed by an experienced physician , using a Philips EPIQ 7CFirst, we assessed LV morphology and function by M-mode and 2D echo. Standard echocardiographic parameters included LV end-diastolic (LVEDD) and end-systolic (LVESD) diameters, LV end-diastolic (LVEDV) and end-systolic (LVESV) volumes, interventricular septum (IVS) and posterior wall (PW) thickness. Measurements were indexed for BSA. As surrogates of LV systolic function, we determined the LVSF on M-mode imaging, LVEF by biplane Simpson’s calculation, the mitral annular plane systolic excursion (MAPSE) and the myocardial performance index (MPI). MPI is an index that incorporates both systolic [isovolumic contraction time (IVCT) and LV ejection time (LVET)] and diastolic [isovolumic relaxation time (IVRT)] time intervals. It is, therefore, an expression of both global systolic and diastolic LV function and is calculated with the following formula: IVCT + IVRT/LVET. An MPI ≤0.40 is considered to be normal . LV dimei.e., the ratio between the peak of early diastolic Doppler mitral blood flow velocity (E wave) and the peak of late diastolic Doppler mitral blood flow velocity (A wave); 2) septal and lateral E/E′ wave ratio, i.e., the ratio between the E wave peak and the peak of the early diastolic myocardial velocity (E′ wave) on tissue Doppler imaging.Diastolic function was assessed following the recommendations of the last guidelines . The folThen, STE was used to quantify myocardial deformation (“strain”) as an index of myocardial function . Peak reLastly, we evaluated three-dimensional LV volumes and LVEF. 3D Echo is a novel echocardiographic technology that is based on the acquisition of “volumes” containing heart structures . 3D measurements of volumes and LVEF have been proved to be more accurate and reproducible compared to standard 2D Echo and similar to those obtained with cardiac magnetic resonance (CMR) , 18. ForContinuous variables are reported as means and standard deviations, while categorical variables as numbers and percentages. The analysis of variance test was used to compare continuous variables, whereas nominal variables were compared by Fisher exact test. Correlation analysis was done by Pearson’s test. Statistical significance was set at a p value <0.05.The main demographic and clinical characteristics of the two groups are summarized in 2.Data about the neoplastic disease and treatment of CCSs patients are summarized in Acute lymphoblastic leukemia was the most common form of disease, followed by Hodgkin lymphoma, non-Hodgkin lymphoma and Ewing’s sarcoma; only one patient was affected by neuroblastoma. At the time of the present study, all CCSs were asymptomatic and did not refer any physical limitation.Conventional echocardiographic parameters are shown in vs 38.80 ± 7.26, respectively; p = 0.027). Furthermore, there was no significant difference in LVEF.No significant differences in LV dimensions and volumes were found between the two groups. SF was slightly lower in CCS patients compared to controls, although values were still within the normal range . The difference was related to a significant increase in IVCT in patients , whereas there were no significant differences in LVET and IVRT between the two groups.Global myocardial function evaluated through MPI resulted significantly lower in CCS patients than in controls . In CC patients, an inverse correlation was found between the E/A ratio and the cumulative anthracycline dose , although values were within the normal range in all subjects. No significant differences in LV 3D volumes were found comparing patients and control group.On 3D Echo imaging, LVEF was found significantly lower in CCSs compared with healthy controls  and age at cancer diagnosis or duration of follow-up. Furthermore, no significant differences were found in echocardiographic findings when patients were divided according to sex, age at diagnosis <5 years, cumulative anthracycline dose >250 mg/m² and concomitant radiotherapy (data not shown).A growing number of CCSs have to face lifelong side effects of cancer therapies, some of which affecting the cardiovascular system , 4, 6. IAmong chemotherapeutics, anthracycline are widely used because of their high efficacy for treatment of childhood hematological malignancies and solid tumors, but are also those most commonly implicated in cardiac damage, resulting in an anthracycline-induced cardiomyopathy .There is a strong dose-dependent relationship between anthracycline chemotherapy exposure and risk of congestive HF, with the incidence of cardiac dysfunction also increasing over time . CongestThe cardiotoxicity of anthracycline may be acute, early or late . Acute cAlthough characteristics and course of anthracycline-induced cardiotoxicity are still to be fully elucidated, the most commonly accepted pathophysiological mechanism is oxidative stress. According to this theory, the generation of reactive oxygen species and lipid peroxidation of the cell membrane can induce progressive cardiac remodeling as a late consequence of earlier myocyte injury, resulting in late cardiomyopathy .2, infusion regimen, age younger than 5 years, additional radiation therapy, other concomitant chemotherapies and female sex  and diastolic function (IVRT) and is independent of HR, ventricular geometry and preload/afterload . PreviouAs a decrease in diastolic function often precedes the decline in systolic function , we inveRecently, myocardial strain imaging obtained by STE and 3D echo have been suggested to be more sensitive techniques than standard echocardiography for the earlier detection of subtle changes in myocardial function after anthracycline therapy . Recent Myocardial strain imaging, obtained by STE, evaluates the change in myocardial fiber length as compared to its original length in the plane in which it is measured . Unlike Among newer techniques, 3D echo has been shown to overcome the geometric limitations of 2D Echo for the assessment of LV volumes and EF and has been validated against CMR in assessing the LV volumes and EF in both children  and adulIn our study, we did not demonstrate statistically significant correlations between echocardiographic parameters  and age at diagnosis or duration of follow-up. Similarly, a correlation between the echocardiographic parameters and established risk factors for anthracycline cardiomyopathy could not be documented. This may be due to a small sample size and/or young age of this cohort.In conclusion, our study found significantly reduced 3D LVEF in CCSs compared with healthy controls, despite no significant differences in 2D EF and longitudinal strain values. These findings might support the use of 3D echo for the detection of early LVEF in CCSs.In recent years, cardiac surveillance for early detection of late subclinical cardiac dysfunction in CCSs treated with anthracycline has received increasing attention. Although commonly used, conventional echocardiographic parameters may not detect early cardiovascular damage in these patients. Novel imaging techniques, including ST imaging and 3D echo, have been investigated, but further longitudinal studies are necessary to clarify and optimize their role in routine clinical practice. The challenge with these non-conventional methods is to understand whether an abnormal result may be considered predictive of subsequent overt LV dysfunction, which might allow the identification of patients at risk and undertaking early preventive strategies.Some limitations of our study should be acknowledged. First, we did not perform a preliminary sample size calculation to plan the number of subjects to enroll in the study. However, since previous studies showed that CCSs may have a decrease in LVEF of 10% , 59, we The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.Conceptualization, AnR, AD, AL, and GL. Methodology, PL, VM, and AV. Writing—original draft preparation, AlR, RS, LB, and GA. Writing—review and editing, AD, RS and AL. Supervision, AnR and GL. Statistical analysis, GL, GA, and AV. All authors contributed to the article and approved the submitted version.This work was supported by Fondazione Policlinico Agostino Gemelli IRCCS.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The pulmonary artery catheter (PAC) was introduced into clinical practice in the 1970s and was initially used to monitor patients with acute myocardial infarctions. The indications for using the PAC quickly expanded to critically ill patients in the intensive care unit as well as in the perioperative setting in patients undergoing major cardiac and noncardiac surgery. The utilization of the PAC is surrounded by multiple controversies, with literature claiming its benefits in the perioperative setting, and other publications showing no benefit. The right interpretation of the hemodynamic parameters measured by the PAC and its clinical implications are of the utmost essence in order to guide a specific therapy. Even though clinical trials have not shown a reduction in mortality with the use of the PAC, it still remains a valuable tool in a wide variety of clinical settings. In general, the right selection of the patient population (high-risk patients with or without hemodynamic instability undergoing high-risk procedures) as well as the right clinical setting (centers with experience and expertise) are essential in order for the patient to benefit most from PAC use. Initially, the main purpose of pulmonary artery catheterization, which was first introduced into medicine in 1944  allowed Even though the use of the PAC has declined over the past decades, it remains the preferred invasive hemodynamic method for multiple surgical interventions, such as cardiothoracic procedures including heart transplantation, left ventricular assist device (LVAD) implantation, as well as lung and liver transplants. One of the several advantages of the PAC is the ability to monitor several hemodynamic parameters , pulmonary and peripheral vascular resistance, and mixed venous saturation) as well as therapeutic interventions such as the administration of drugs and right atrial and ventricular pacing .This review will critically examine the role of the PAC in the perioperative setting considering new clinical trials, especially during cardiothoracic surgery.Take-home messages from the included studies regarding the application of the PAC in various clinical settings are summarized in The PAC allows continuous tracking of several hemodynamic variables, which seems particularly valuable in critically ill high-risk patients with circulatory dysfunction. The measurement of cardiac output can differentiate shock states into hypovolemic etiology (low cardiac output with low filling pressures), cardiogenic etiology (low cardiac output and high filling pressures), and distributive etiology (high cardiac output and low systemic vascular resistance). Furthermore, the measurement of cardiac output and left and right filling pressures (pulmonary artery wedge pressure (PAWP) and central venous pressure (CVP), respectively) allows the distinction between left ventricular (LV) or right ventricular (RV) dysfunction or global dysfunction. For RV dysfunction, the PAC can further differentiate between RV dysfunction predominantly related to increased afterload (high pulmonary artery pressure (PAP)) versus dysfunction related mostly to pump failure (high CVP and low PAP) ,11.Despite these advantages, the PAC has seen a decline in its usage, which has been justified with the arguments that it is an expensive, invasive technique which has still not shown to improve patient outcomes. In the ’90s and 2000s, several large, randomized, adequately powered studies have been published regarding the use of the PAC in various settings: general non-cardiac surgery , vasculaIn 2003, the American Society of Anesthesiology published recommendations pertaining to the perioperative use of PACs . The tasThe evidence-base for PAC use in patients undergoing cardiac surgery is scant, particularly lacking prospective randomized trials, so much of the evidence is derived from retrospective or observational studies. Furthermore, several contradicting studies exist regarding the use of a PAC, with some demonstrating benefits, others showing disadvantages, and still others having neutral results.p < 0.001), decreased cardiopulmonary morbidity , and increased infectious morbidity . Even though no mortality benefit could be observed in this study, a reduced length of stay and decreased cardiopulmonary morbidity, albeit at the cost of an increased infectious morbidity, suggests an overall potential benefit associated with PAC-based monitoring in this population [A retrospective cohort study  includinp = 0.004), longer ICU length-of-stay , and more postoperative red blood cell transfusion  compared with the group without PAC insertion. Otherwise, perioperative outcomes were similar between the two groups, including the cardiopulmonary bypass time (p = 0.593), ischemic time (p = 0.420), stroke (p = 0.498), sepsis (p = 0.576), and new postoperative renal failure (p = 0.563). Operative mortality was 2.4% for both groups and thus not associated with PAC insertion status. The findings in this study suggest that PACs may have limited benefit in cardiac surgery and may even have unintended consequences for postoperative management [A large observational study  includinp = 0.0048). No statistically significant differences were noted in the incidence of cardiac arrest or death between groups [This study is in contrast to a large retrospective study , which in groups .Since a clear correlation between right ventricular dysfunction and mortality exists, the use of a PAC to measure the right ventricular function has been used widely in the operating room during cardiac surgery. More recently, 3D-transesophageal echocardiography (TEE) has been increasingly utilized to measure right ventricular volumes. A recent, small, prospective observational study  aimed toAnother small, prospective observational study  assessedRaymond et.al.  describeAdvanced cardiovascular monitoring, such as with a PAC, has routinely been used in clinical practice to manage patients undergoing liver surgery. About 8% of patients with chronic liver disease have underlying portopulmonary hypertension, and in patients with severe pulmonary hypertension (mean pulmonary artery pressure >50 mmHg) mortality in the perioperative period during liver transplantation approaches 100%. The PAC may be useful in differentiating the causes of pulmonary hypertension, including high cardiac output and low vascular resistance states and increased blood volume with high pulmonary artery occlusion pressure, which result in a better prognosis than patients with elevated pulmonary vascular resistance .p = 0.03) and the lowest 30-day mortality rate . However, the TEE + PAC group also had the highest rate of a new postoperative need for dialysis . When TEE and PAC are being compared with each other, PAC use was associated with a shorter length of hospitalization (9.1 vs. 10.3 days) as well as a lower 30-day mortality rate (3.5% vs. 12.8%). This study showed that the combination of PAC and TEE leads to better outcomes in terms of the length of hospitalization and 30-day mortality, albeit at the cost of an increased need for dialysis postoperatively [A recent retrospective study  includedEven though there is a paucity of data on the use of the PAC in lung surgery, its routine use is still common in the western world. Severe pulmonary hypertension is one of the most common indications for PAC use, given its high reliability in measuring beat-to-beat pulmonary artery pressure in the operating room . Besides2), oxygen utilization, oxygen delivery, oxygen extraction, and PvCO2) makes it especially useful in the management of patients with shock. As such, current guidelines recommend the use of the PAC over other less invasive devices in patients with severe or refractory shock to monitor cardiac function and CO [The ability of the PAC to measure several important hemodynamic variables as well as tissue perfusion variables .Arrhythmias .Catheter knotting.Pulmonary thrombosis and infarction.Endothelial or valvular damage.Colonization and bacteremia.Pulmonary artery rupture.Complications arising from venous access are the same as those occurring during the insertion of a central venous catheter. In a multicenter study comparing hemodynamic management guided by a PAC versus a central venous catheter, complications were uncommon and were similar in both groups. Positive blood cultures following catheter insertion were found equally often in both groups . CardiacPulmonary artery rupture, although an exceptionally rare complication, is probably the most feared complication due to its high mortality rate (70%) . OverinfWhen analyzing the current data published on the use of PACs, a reasonable conclusion is that PAC use is reserved to centers with significant experience and expertise. The PAC generally is used to monitor and guide therapy in high-risk surgical patients undergoing high-risk procedures, those at high risk for hemodynamic instability, and those who are judged more critically ill by a variety of clinical means, especially if elderly and suffering from other systemic diseases.There exist a variety of less invasive alternatives to the PAC for CO measurement with their respective advantages and disadvantages . ProbablIn conclusion, in the perioperative setting PAC remains the gold standard for CO measurement. Obviously, the PAC itself has no potential for benefit unless it guides therapies that improve patient outcomes. Future research should focus on defining subgroups of patients who might benefit from use of a PAC, as well as defining effective therapeutic interventions based on the hemodynamic information gained from the PAC.


The aim of the study is to investigate the correlation between LASr and NT-proBNP and its prognostic value with regards to the composite endpoint of HF hospitalization and all-cause mortality within 1 year.The left atrium (LA) is a key player in the pathophysiology of systolic and diastolic heart failure (HF). Speckle tracking derived LA reservoir strain . Compared to NT-proBNP, LASr predicts the endpoint with a comparable specificity (83% vs. 84%), however with a lower sensitivity (70% vs. 61%).We included 174 HF patients, 43% with reduced, 36% with mildly reduced, and 21% with preserved ejection fraction. The study population showed a strong inverse correlation between LASr is inversely correlated with NT-proBNP and a good echocardiographic predictor for the composite endpoint of hospitalization and all-cause mortality in patients with HF.LASTrial registration:https://www.trialregister.nl/trial/7268 Heart failure (HF) is among the leading causes of morbidity and mortality worldwide . Early rr) by speckle-tracking echocardiography for both diagnosis and prognosis of HF  with a median LASr 27% [20–35]. On subgroup analysis, patients with HFrEF had significantly larger LVEDV and prevalence of mitral valve regurgitation was higher compared with HFmrEF (p < 0.01). LA size did not differ significantly between HFrEF and HFpEF patients, however LASr was lower in the HFrEF compared with HFpEF and HFmrEF patients   142 ml [100–195], and median LAVI 37 ml/mp < 0.01, HFpEF p = 0.02) (Table Median NT-proBNP (568 pg/mL 276–1114]) was significantly higher in the HFrEF group (HFmrEF 76–1114) r (r = − 0.55 p < 0.01), which improved after 10log-transformation of NT-proBNP   Fig. . For ther . E/A and E/e’ ratio had a moderate inverse correlation with LASr .Both deceleration time of early mitral inflow (E) and early diastolic mitral annular velocity (e’) had a weak correlation with LASTwenty-three patients 13%) reached the composite endpoint of all-cause mortality and heart failure hospitalization , however not from LVEF and NT-proBNP (p = 0.10 and p = 0.25). Figure r (Panel A) and NT-proBNP (Panel B). Patients with LASr ≤ 17% showed significantly worse survival than patients with LASr > 17%. Patients with NT-proBNP ≥ 1191 pg/mL also showed significantly worse survival.Results of receiver operating characteristic (ROC) analysis for all predictors of the endpoint are shown in Fig. r is a strong echocardiographic predictor of the composite endpoint of HF hospitalization and all-cause mortality. Compared to NT-proBNP, LASr predicts the endpoint with a comparable specificity (83% vs. 84%), however with a lower sensitivity (70% vs. 61%). Also, LASr correlates strongly with 10log-transformed NT-proBNP levels.The key findings of the present study are as follows. First, LASr has enhanced prognostic value beyond conventional echocardiographic measures to discriminate which heart failure patients are at greater risk for hospital admission or death. For HF subgroups, Carluccio et al. [r by speckle-tracking strain echocardiography had powerful prognostication in patients with HFrEF and HFpEF, respectively.LASo et al.  and Freeo et al.  showed tr, are in line with our results. Al Saikhan [r had moderate inverse correlation with NT-proBNP (r = − 0.42) [r and a log-transformation of NT-proBNP levels was not reported, although it has been shown that plasma concentrations of NT-proBNP follow a log-normal distribution in patients with HF [Although limited in number, previous studies that investigated the correlation between NT-proBNP and LAS Saikhan  demonstr − 0.42) . In both with HF . Prastar with HF  evaluate with HF .r. Moreover, LASr can accurately categorize patients based on a normal or elevated LV filling pressures [Assessment of LV filling pressure has important diagnostic and prognostic implications in patients with HF , 11. Altressures , 20.r provides potentially clinical relevance in the detection of LV diastolic dysfunction, because LASr detects subtle dysfunction, even before the LA begins to enlarge [r decreases in a linear fashion as LV diastolic dysfunction progresses [r should not be used in patients with atrial fibrillation [r, that seemed to precede conventional measures of LV diastolic dysfunction [r is not only influenced by diastolic, but also by systolic LV function. As LA expansion is also determined by the base-to-apex displacement during LV systolic contraction [r. Thus, LASr correlates with both LV filling pressures and systolic performance.In HFpEF a fortiori, elevated filling pressures are the main physiologic consequence of the diastolic dysfunction . Current enlarge . LASr deogresses . In lineogresses  encouragillation . We prevfunction . Moreovetraction , any conThe LA seems to have a central role in HF. LA function can be easily studied using speckle-tracking strain echocardiography. The LA strain measurements should be included in the standard evaluation of outpatients with heart failure, because it can stratify their risk for hospital admission and death more reliable than LVEF. Further research is need if a closer follow-up of these patients will reduce their morbidity and mortality.r. Fourth, in this prospective study a combined endpoint of HF hospitalization and all-cause mortality has been chosen. Cardiovascular death might have been a stronger endpoint. However, the exact cause of death was not known in all of our HF patients. Finally, in 7% of the study population, LASr could not be analyzed due to poor image quality.Although the current study is based on a real-world, prospective, observational data of an outpatient HF population referred to the echocardiography lab, the subgroups of different HF types were relatively small. Second, the number of events was too small to perform a multivariate Cox regression analysis. A logistic regression with NT-proBNP and echocardiographic parameters did not result in an improvement in AUC. However, follow-up research with a larger population and more events is needed to draw conclusions on the AUC of combined laboratory and echocardiographic parameters. Third, the length of follow-up in the current study was limited to 1 year, so we were unable to determine the long-term prognostic value of LASr is a strong echocardiographic predictor of the composite endpoint of HF hospitalization and mortality. LASr is inversely correlated with NT-proBNP and predicts the endpoint with a comparable specificity.LAS


AF in HCM patients seems to be LA as well as LV disease. Revealing lower strain for LV, in addition to lower LA strain, may have an important impact on accurate characteristics of HCM patients with AF history.Atrial fibrillation (AF) is an important arrhythmia in hypertrophic cardiomyopathy (HCM). We aimed to explore whether a complex evaluation of the left ventricle (LV) using modern echocardiography techniques, additionally to the left atrium (LA) boosts the probability of AF diagnosis. Standard echocardiography, 2D and 3D speckle tracking, were performed for LA and LV evaluation in HCM patients and healthy volunteers. Of 128 initially qualified HCM patients, 60 fulfilled included criteria, from which 43 had a history of AF, and 17 were without AF. LA volume index and peak strain, LV ejection fraction, and strains were significant predictors of AF. In addition, 2D global longitudinal strain (GLS) for LV at cut off −16% turned out to be the most accurate predictor of AF (OR 48.00 [95% CI 2.68–859.36],  Atriasc SCORE ,5,6,7. Tsc SCORE ,8. Thus sc SCORE ,10,11. Fsc SCORE ,10. Recesc SCORE ,15,16,17Recently, the evaluation of LV function, not only LA, in AF prediction enjoys growing interest. The connection between the LV and LA functions is well known. The LA reservoir function (consisted of active relaxation and passive dilatation)  is assocMoreover, strains calculated in three-dimensional (3D) STE could have a complementary role in HCM patients’ assessment due to the potential ability to overcome some of the intrinsic limitations of 2D STE in assessing complex LV myocardial mechanics offering additional deformation parameters. However, it has been studied so far only in a few publications ,28,29,30Our study aimed to explore the value of LV assessment, using modern 2D and 3D echocardiography techniques in revealing the history of AF in HCM patients. We tried to answer whether the through LV assessment additionally to LA boosts the probability of AF diagnosis.A prospective analysis of retrospectively enrolled consecutive patients of the Outpatient University Clinic in Gdansk with HCM diagnosis was performed with data collected from October 2013 to October 2018. The HCM diagnosis was based on the current criteria: determined by echocardiography, at least one or more LV segmental hypertrophy ≥ 15 mm, which could not result from abnormal loading condition (such as hypertension or aortic stenosis) . The AF Echocardiography examination was performed during sinus rhythm, using the GE VIVID E9 machine , equipped with phased-array transducer (M5S) and 3D (4V) probe. In addition, 2D echo sets were obtained following applicable recommendations using parasternal and apical views : the imaLA diameter size (LADs) was measured in the parasternal view. The LA and LV volumes and LVEF were measured by Simpson’s Biplane Method in the apical 2D views. LV mass was calculated as it was described in the literature . The LA 2D STE parameters were obtained following the applicable recommendations . For the3D measurements were obtained following applicable recommendations ,38. The p < 0.05 were considered significant. The statistical analysis was conducted with and R 3.1.2. environment .Continous data are presented as median (25th percentile–75th percentile), whereas categorical data are expressed as proportions. The Shapiro–Wilk test was performed to determine whether data were normally distributed. The majority of the analyzed parameters did not have a normal data distribution, even after logarithmic data transformation. Therefore, we selected appropriate statistical analysis methods based on nonparametric tests. Comparisons between groups were performed with the Mann–Whitney U-test for continuous variables and Pearson’s chi-square test for categorical variables, as appropriate. Intra- and inter-observer reproducibility was assessed on 20 randomly selected patients: intra-class correlation coefficient (ICC), coefficient of variation (CV), the lower and upper limits of agreement, and mean bias (Bland–Altman test) were calculated. The clinical significance of ICC was interpreted as follows: excellent, ICC ≥ 0.80; good, 0.60 ≤ ICC < 0.80; moderate, 0.40 ≤ ICC < 0.60; and poor, ICC < 0.40 . The accAmongst 128 consecutive HCM patients, finally, we enrolled 60 , from whAmong standard echocardiography, LADs, LAA index, LAV index, and diastolic function parameters (Em and E/Em) differed significantly between HCM patients and healthy persons; regarding the comparison between AF+ and AF− patients, the only parameter significantly differed between the two groups was LVEF, which was lower in AF+ patients . The accPrespecified cut-off values calculated in the ROC analysis are presented in LAVi, LA peak strain, LV strains, and LVEF with prespecified cut-off values calculated from the ROC curves were significant predictors of AF in the univariate logistic regression analysis that was not confirmed for LADs .p = 0.001. A combination of LV GLS worse than −16% and LA peak strain lower than 22% in logistic regression analysis increased the probability of AF revealing OR 76.36 (4.13–1411.36), p = 0.001.LV GLS turned out to be the strongest predictor of AF: OR 48.00 (2.68–859.36), The inter- and intra-observer variability analysis shows similar and satisfactory results for the measured STE parameters: for 2D LA and LV strains and 3D LV strains . The ICCThe main finding of the present study is revealing the complex mechanism of AF in HCM patients based not only on the LA dysfunction but the LV dysfunction as well. We confirmed that the measurement of the LV strains additionally to LA boosts the probability of AF diagnosis. To the best of our knowledge, this is the first study where a thorough analysis of the LV, including 2D and 3D speckle-tracking techniques, additionally to LA assessment, was performed in AF diagnosis revealing in HCM patients.p = 0.078). LAVi, as the following standard echocardiography parameter, turned out to be better than the LADs predictor of AF history, being in line with data from the literature [p = 0.005.LADs, mentioned in the European HCM guidelines  as the oterature ,10,11. Iterature . Howeverterature ,16: in Dterature , that waOur study revealed the differences in the LV strains between the HCM patients with and without AF , postulaTo the best of our knowledge, our research is one of the first studies concerning the relationship between the LV strain and AF occurrence in patients with HCM. Russo et al. in the Northern Manhattan Study of 675 patients showed that a value measured from 2D GLS for LV worse than –14.7% was a strong predictor of AF appearance , but thiOur study’s innovation is that 3D STE for the LV evaluation may help diagnose AF in HCM patients. Indeed, 3D echocardiography plays a particular role in assessing HCM patients due to the complex mechanics of LV contraction ,29,44 T. Tanaka The knowledge of the occurrence and early diagnosis of AF in HCM patients is of great clinical value. Widely available and easy to perform, STE may be helpful in the identification of HCM patients with a high risk of AF appearance. Strain for the LA enjoys a growing clinical interest in this issue. GLS for LV measured by 2D STE is a well-studied, validated, and accessible parameter, useful in many clinical conditions, including HCM patients. Diagnosis of AF in this group could be another essential clinical application for this parameter, particularly in combination with the LA strain measurement. Furthermore, 2D LV GLS worse than −16%, in addition to 2D LA strain below 22%, allows for AF diagnosis with high probability. Moreover, 3D STE analysis opens up further clinical possibilities in AF risk estimation of HCM patients.Due to the necessity of selecting a clinically homogeneous group of patients, the most critical limitation is that this study is a single-center analysis based only on a small group of patients with taking into account only patients with good echocardiographic image quality, especially considering the evaluation of strain. The small number of patients translated to the lack of multivariate analysis and the lack of other kinds of statistics . Contrary to complex 3D STE parameters, we did not analyze 2D circumferential and radial strains as an analysis that requires a complex approach. The next limitation is that LA strain was analyzed using the software for LV strain analysis due to the lack of appropriate software dedicated to LA. Furthermore, GLS was assessed using only one of the available vendor platforms; therefore, the results may differ slightly from those received with alternative software algorithms.AF in HCM patients seems to have a complex mechanism based on LA and LV dysfunction. Modern echocardiography techniques could help for better discrimination of HCM patients with a history of AF, which may have a potential clinical impact due to the necessity of anticoagulation treatment in such patients regardless of the other known risk factors for thromboembolic complications. Further research based on a more extensive group of patients is strongly recommended.