With the emergence of transcatheter solutions for the treatment of tricuspid regurgitation (TR) increased attention has been directed to the once neglected tricuspid valve (TV) complex. Recent studies have highlighted new aspects of valve anatomy and TR etiology. The assessment of valve morphology along with quantification of regurgitation severity and RV function pose several challenges to cardiac imagers guiding transcatheter valve procedures. This review article aims to give an overview over the role of modern imaging modalities during assessment and treatment of the TV. Since the recent emergence of percutaneous valve interventions as a possible alternative to surgery or medical treatment, tricuspid valve (TV) disease has attracted growing attention. Although tricuspid regurgitation (TR) of any severity is present in about 70% of the population , in the Multiple observational studies have reported worse survival in patients with severe TR, irrespective of left and right ventricular function, pulmonary artery pressure, age, gender and co-morbidities , 5–10. IImaging the TV and grading TR is challenging as transfer of existing knowledge and recommendations from the left side of the heart is not always possible. In contrast to the mitral valve, the TV operates in a low pressure environment with slower jet velocity. In addition, valve geometry, TR proximal flow convergence zone, and jet morphologies are more complex, making the usual tools and geometrical assumptions less accurate . The higAutoptic studies have enhanced the anatomical understanding of the TV –19. IndeThe healthy tricuspid annulus has a three-dimensional saddle-shaped elliptical geometry , 21–23. TR etiology can be divided in primary (or organic) TR due to leaflet abnormalities, and secondary  TR due to annular and right atrial, or right ventricular dilation . DiseaseTR leads to volume overload and further RV and RA dilation, resulting in annulus dilation, papillary muscle displacement and leaflet tethering, also influenced by elevated pulmonary artery pressure, further aggravating valve dysfunction , 31. TR Chronic atrial fibrillation can be either the cause or the result of TR. Studies report a high overall prevalence of chronic atrial fibrillation in patients with moderate or severe TR (up to 68%) with a yearly incidence of 28% in the setting of associated left-sided valvular heart disease and 13% in isolated TR .TR in the presence of cardiac implantable electronic devices-leads (CIED) is a topic of growing concern due to the rising number of implantations. New-onset significant TR after CIED placement has been observed in up to 38% of the patients, either resulting from direct valve injury or adverse interaction with the leaflets, most commonly affecting the septal leaflet , or the Imaging the TV is associated with particular challenges summarized in Due to the anterior position of the RV close to the chest, transthoracic echocardiography usually provides satisfactory imaging quality for severity grading . AdvanceAn integrative approach considering identical parameters using different imaging modalities is likely to improve the diagnostic accuracy.Quantitative and semi-quantitative parameters considered useful for grading TR include the following:2. It is physiologically influenced by direction, momentum and velocity of the jet and the systolic pressure difference between RV and RA  , but witTricuspid inflow velocity can be used as a complementary method to grade TR. A peak tricuspid E-wave velocity >1.0 m/sec has been associated with right ventricular pathology  and seve2 have been proposed  assessed by quantitative Doppler and is calculated as the antegrade tricuspid diastolic SV minus the left ventricular or right ventricular outflow forward SV. In the presence of more than mild aortic regurgitation, the right ventricular forward SV should be preferred, and vice versa. In both cases, the SV is obtained from the diameter (D) and the velocity time integral (VTI) of either the right or left ventricular outflow tract as (D/2)The tricuspid diastolic SV by quantitative Doppler is calculated through multiplication of the tricuspid annular area (preferably measured on 3D multiplanar reconstruction) by the pulsed-wave Doppler VTI through the annulus , 55. TheUsing 4D MSCT the regurgitant volume and fraction are derived from the difference between RV and LV stroke volume obtained by ventricular volumetry. Higher saptial resolution may represent an advantage, but cutoffs to grade TR severity have not been established yet , 57. TabUsing CMR, the TR jet can be visualized based on its signal void with cine imaging. Quantitative TR severity is calculated indirectly. The forward flow volume is obtained from through-plane phase-contrast velocity mapping in the pulmonary artery. After substraction of the forward volume measured in the pulmonary artery from the total RV stroke volume assessed by RV volumetry (ciné steady-state free precession imaging), absolute TR regurgitant volume and fraction can be calculated . More re2 indicates severe TR. Calculation of the EROA according to the PISA method is based on the assumption of a circular orifice and thus disregards the complexity of the TV, resulting in underestimation of TR severity in one third of patients. Assessment of PISA by 3D-color echocardiography may overcome this limitation by providing a more realistic picture of the actual geometry of the flow convergence zone. However, it may underestimate the actual surface area of the PISA due to angle dependency of the color-Doppler. In addition, PISA only accounts for a single time point and therefore does not integrate the potentially dynamic nature of the flow  ≥ 40 mmthe flow . Alternathe flow . A possithe flow .Instead of using a single PISA to calculate the regurgitant volume, the concept of integrated PISA accounts for temporal changes of the regurgitant flow during systole. With this method, a 3D PISA is reconstructed for each frame of the acquired loop. The flow of each PISA corresponds to its area multiplied by the chosen Nyquist velocity. As explained in As recently described for the mitral valve , measureIn our experience, the values obtained using multiplanar reconstruction  are geneSince many patients present at a very advanced stage of the disease, current thresholds for severity grading may not sufficiently reflect the variability of the clinical presentation. For this reason, a new grading scheme including the two additional grades “massive” and “torrential” with corresponding cut-offs has recently been proposed , 65 and RV function has an important prognostic value in patients with TR  and, in RV ejection fraction is highly dependent on pre- and afterload, and for this reason, probably suboptimal for the evaluation of RV function in the presence of pulmonary hypertension and/or severe TR , 71. TriTo overcome these specific drawbacks, new methods have been proposed. Using 2D spackle tracking, the longitudinal strain can be derived in all RV segments. This measure correlates well with the RV ejection fraction by CMR  and has In contrast, 3D echocardiographic volumetric quantitation of the RV in different planes is limited by the need for clear delineation of the endocardial borders. Published data, which may overestimate the feasibility of this complex method, show a good correlation for systolic function, but a systematic underestimation of volumes in comparison to CMR , 73, 80.Although less investigated, RV function, dimensions, and volumes may also be reliably obtained from a dedicated 4D electrocardiogram-gated MSCT  and normMultimodality imaging is essential for patient selection as well as procedural planning. Moreover, it may help to anticipate and prevent complications and thereby improve outcomes. After thorough assessment of the underlying mechanism of TR, RV function and the exclusion of severe pulmonary hypertension, patients with persisting symptoms despite guideline-directed medical therapy should be evaluated for an intervention by the Heart Team. In patients with concomitant valvulopathy or coronary artery disease requiring surgical revascularization, open-heart surgery remains the first-line treatment. Patients at low surgical risk with isolated severe TR may also be referred for surgical valve repair or replacement, although evidence of an impact on survival is lacking , 84 In p2, a tenting height ≥ 0.8 cm and a tenting volume ≥ 2 cm3 are predictors of procedural failure for tricuspid repair  and if applicable, precise CIED-lead location and assessment of its relation to the leaflets (mobile vs. adherent) is crucial for procedural planning of any TV intervention. Especially the TEE short axis view, obtained from transgastric, or the surgical view, acquired by 3D imaging, delivers valuable anatomical information. When aiming for TV repair using leaflet approximation, the exact jet location as well the anticipated implantation strategy (triple orifice vs. bicuspidization), and the number of devices has to be determined. Coronary angiogram should also be part of pre-procedural work-up to confirm patency of the RCA.2 for the annular area is indicative of severe TR  is increasingly used to guide transcatheter TV repair, currently as an adjunct to TEE –109. PlaFusion-imaging integrating echocardiography and/or MSCT, and fluoroscopy require further validation for tricuspid interventions. However, it has the potential to simplify the procedural steps through sophisticated visualization of anatomical structures and catheters/devices in relationship to each other , 110.MSCT provides the necessary information for 3D printing of anatomical models than can be used to simulate and train complex TV procedures.in vitro studies compared the echocardiographic evaluation of multiple regurgitant orifices with an independent method (Assessment of interventional TR treatment efficacy using echocardiography can be challenging, especially after leaflet approximation procedures and/or when multiple TR jets are created. In addition, the implanted devices may produce acoustic shadows impairing correct evaluation of proximal flow convergence and vena contracta. Until now, only t method . From a The tricuspid valve complex challenges imaging specialists and interventional cardiologists in many respects. Patients with TR constitute a heterogeneous and polymorbid population who frequently present late during the course of the disease. Imaging plays a crucial role for the understanding of the natural progression and underlying mechanisms of the disease, as well as for the guiding of transcatheter interventions. Further refinements of current imaging methods will help to better select the appropriate device for the right patient and simplify transcatheter procedures.All authors have made substantial contributions to the conception of the work. It has been drafted by MW and FP and has been critically revised by all authors for important intellectual content. All authors have given their approval for publication of the content and have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.SW reports having received research grants to the institution from Abbott, Amgen, Bayer, BMS, Biotronik, Boston Scientific, CSL Behring, Edwards Lifesciences, Medtronic, Polares and Sinomed. TP reports having received research grants to the institution from Edwards Lifesciences, Boston Scientifc and Biotronik, and speaker fees from Biotronik and Boston Scientific. OK has received speaker's fees from Edwards Lifesciences, and is a consultant for Abbott Structural and Boston Scientific. RH is the Chief Scientific Of ficer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for which she receives no direct industry compensation; and has received personal fees from Abbott Vascular, Boston Scientific, Bayliss, Navigate, Philips Healthcare, and Siemens Healthineers. The remaining 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.


Congenital heart disease (CHD) affects 0.8% of live births and over the past decades technical improvements and large-scale repair has led to increased survival into adulthood of over 95% of the new-born. A new group of patients, those who survived their congenital heart defect, has emerged but late complications including heart failure, pulmonary hypertension (PH), arrhythmias, aneurysms and endocarditis appeared numerous, with a huge impact on mortality and morbidity. However, innovations over the past years have changed the landscape of adult CHD dramatically. In the diagnostic process important improvements have been made in the use of MRI, biomarkers, e‑health concepts and 3D visualisation of anatomy. Care is now concentrated in specialised centres, with a continuous emphasis on education and the introduction of weekly multidisciplinary consultations on diagnosis and intervention. Surgery and percutaneous intervention have been refined and new concepts applied, further reducing the burden of the congenital malformations. Research has matured from case series to global networks. Currently, adults with CHD are still facing high risks of early mortality and morbidity. By global collaboration and continuous education and development and innovation of our diagnostic and therapeutic arsenal, we will improve the perspectives of these young patients. Excellent care for adult patients with congenital heart disease.Establishment of a national registry and DNA bank (CONCOR).Important contribution in scientific research in adult congenital heart disease.Leading role in global research networks.Birth prevalence of congenital heart disease (CHD) is estimated to be 8 cases per 1000 live births and up to 95% survive until adulthood  and computed tomography (low radiation and high resolution), MRI has emerged over the past few decades as the superior imaging modality for complex ACHD patients. Rapid, high-resolution imaging of complex anatomy and accurate quantitative assessment of physiology and function have become possible . New tecUpcoming techniques are 3D printing, in which computed tomography or MRI data may be used to reconstruct the heart and vessels . AnotherBiomarkers are becoming increasingly used in ACHD as clinicians start to recognise the diagnostic and prognostic significance. Brain natriuretic peptide, a cardiac hormone secreted by cardiac myocytes, responds to ventricular wall stress secondary to volume and pressure overload and is elevated in most adults with complex CHD . TroponiE‑health is an upcoming modality with high potential. E‑health is a concept covering several processes from telemedicine, teleradiology, teleconsulting, monitoring vital signs, to educational websites. The greatest impact seems to be in the early diagnosis of complications. In ACHD patients it has been shown that e‑health is feasible with high adherence enabling early detection of arrhythmias, hypertension and HF. This may lead to a swift therapeutic response or remote reassurance in case of normal findings .The outstanding improvements in surgical and interventional techniques over the last decades have resulted in a substantial decrease in mortality and morbidity of the ACHD population. This result has evolved from a strategy of not only restoring anatomy, function or haemodynamics, but also from preventing and solving long-term complications. Most complications are related to valvular dysfunction and fibrosis as a result of longstanding volume or pressure overload and the intervention itself, while endocarditis remains relevant. Complications of the modern Western lifestyle such as atherosclerosis, diabetes and obesity need to be taken into account as well.HF phenotypes in ACHD can be categorised into those with uncorrected defects, a repaired or palliated status and a failing single ventricle physiology . While iArrhythmogenesis is induced by a myriad of variables including anatomical defects, surgical scarring, hypoxaemia, haemodynamic sequelae and genetic factors . Any newDespite medical advances, the prevalence of endocarditis did not decrease . AlthougACHD patients are not exempt from acquired cardiovascular diseases. Compared with the general population, the relative risk for developing coronary artery disease (CAD) is between 4.6 and 12.0 for men and women aged 20 years, respectively . Not onlPH is a relatively common complication in CHD as approximately 4–10% will develop PH with an incidence of 35% in the elderly . It signPrevention of pulmonary arterial hypertension (PAH) is of paramount importance. Significant shunts should be closed with surgical or transcatheter repair shortly after diagnosis. Follow-up of closed defects is obligatory to detect PAH in an early phase.Treatment of PAH in CHD should be a multidisciplinary team approach and individualised for each patient according to the underlying aetiology, haemodynamics and clinical status. Supportive therapy is mainly given to avoid or treat complications related to PH-CHD and includes diuretics to unload the right ventricle, oxygen administration, psychosocial support, and supervised rehabilitation.In the last decades, several drugs interfering with one of the three pathways leading to pulmonary vascular remodelling have become available. In the past, endothelin receptor antagonists, e.g. bosentan, have shown favourable outcome in exercise capacity and pulmonary haemodynamics in patients with Eisenmenger syndrome . HoweverIn the last decade, development of percutaneous techniques has significantly contributed to the management of patients with ACHD  is a low-risk surgical procedure to strengthen the aortic root in connective tissue disorders such as Marfan’s syndrome and probably also degenerative disorders  and international networks such as the ISACHD and the EuroGUCH facilitate worldwide collaborative ACHD research and education. Several international initiatives have been undertaken to improve efficacy, such as the NOTE Registry, a global study assessing the efficacy and safety of non-vitamin K oral antagonists in preventing thromboembolic complications in ACHD and the ROPAC study, describing the outcome of pregnancy in cardiac patients, including ACHD , 39. MucIn the past decades tremendous progress has been made in ACHD care. However, we are facing new challenges to further reduce early mortality and morbidity. By applying improvements in diagnostics and innovations in our therapeutic arsenal together with global collaboration and education, our ACHD patients may benefit from these future achievements.


Despite the increasing interest in sleep and dream-related processes of emotion regulation, their reflection into wake and dream emotional experience remains unclear. Here, we aimed to assess dream emotions and their relationships with wake emotions through the modified Differential Emotions Scale , which includes a broad array of both positive and negative emotions. The scale has been first validated on 212 healthy Italian participants, in two versions: a WAKE-2wks form, assessing the frequency of 22 emotions over the past 2 weeks, and a WAKE-24hr form, assessing their intensity over the past 24 h. Fifty volunteers from the wider sample completed the WAKE-24hr mDES for several days until a dream was recalled, and dream emotions were self-reported using the same scale. A bifactorial structure was confirmed for both mDES forms, which also showed good validity and reliability. Though Positive and Negative Affect  were balanced in dreams, specific negative emotions prevailed; rmANOVA showed a different pattern  in wake (both WAKE-2wks and WAKE-24hr), with a decrease of PA and an increase of NA in the dream compared to previous wake. No significant regression model emerged between waking and dream affect, and exploratory analyses revealed a stable proportion of PA and NA (with prevailing PA) over the 3 days preceding the dream. Our findings highlight a discontinuity between wake and dream affect and suggest that positive and negative emotions experienced during wake may undertake distinct sleep-related regulation pathways.  The importance of sleep for healthy emotionality is now widely acknowledged, as testified by the amount of evidence produced on the topic in the last decade  in thesIndeed, several models propose that dreaming actively participates in the regulation of prior wake emotions, by facilitating the resolution of emotional conflicts ,17, enhaThe idea of a close connection between emotions experienced during wake and those of the dreams is thus central throughout the various models. At the biological level, it is supported by the existence of largely overlapping neural networks sustaining both (REM) dreaming and emotional processing (extensively reviewed in ). HoweveSome indications may come from the psychological data on dream emotions accumulated up to now. Numerous studies assessed associations between dream emotions  and several aspects of waking emotionality. For instance, trait anxiety , stress Overall, these results suggest that the predominant valence of waking affect has a tight correspondence with the valence of dream emotionality. However, these data refer to general measures of affective states, which are multicomponential in nature and, though partially overlapping, should be distinguished from the construct of emotion . SpecifiHowever, the paucity of existing data does not yet allow to clearly support any of the aforementioned hypotheses linking waking and dream emotions. Therefore, here we conduct an exploratory study with the aim to investigate the relationships between waking emotions and those of the subsequent night dreams using a self-report instrument, the modified Differential Emotions Scale mDES ,48), whi, whi48])In this study, we use three versions of the mDES: in addition to the one assessing dream emotions (DREAM mDES), we adopted two further versions in order to assess wake emotions across two different time frames. The WAKE-24hr form refers to the intensity of emotions in the last 24 h  and the other (WAKE-2wks form) refers to the frequency of presentation of each emotion over the past two weeks.(a)To investigate the general emotional tone of dreams and the frequency of specific emotions in dreams through a repertoire of emotions broader than the one mostly used in dream literature;(b)To assess the associations of dream emotions with emotions of the previous day and previous weeks, as well as possible differences in the intensity and frequency of emotions across the dream and the waking periods.Therefore, the aims of this study are the following:As part of this study, the mDES ,48 has aFour hundred volunteers from the cities of Naples and Caserta  were screened through a brief ad-hoc interview to collect general demographic data and information on medical condition and life habits. The interview was conducted via telephone by a psychologist of the Sleep Lab of the University of Campania. Two hundred and twelve healthy participants  were thus selected for the study, according to the following inclusion criteria: absence of any relevant somatic or psychiatric disorder, no sleep apnea or respiratory disorder symptoms, having a regular sleep-wake pattern, absence of sleep disorders; no history of drug or alcohol abuse, and limited caffeine  and alcohol (no more than 250 mL per day) consumption.n = 212) participated in the first part of the study, i.e., the validation of the Italian version of the modified Differential Emotions Scale . The. Then = le (mDES  and werele (mDES ), to colle (mDES ) to asseduring that particular day. This had to be done until the day they recalled a dream. On the morning they recalled a dream, they had to fill in the DREAM mDES, specifically referring to the emotions experienced during the dream. Data collection was thus ended as soon as the mDES ratings of one dream were provided by each participant.Of the 212 participants included in the validation study, 50  volunteered to take part in the second part of the study, i.e., the assessment of associations between waking and dream emotions. Participants received ten copies of the mDES WAKE-24hr version, with the instruction to fill one in each night at bedtime, referring to the emotions experienced The study design was submitted to the Ethical Committee of the Department of Psychology, University of Campania “L. Vanvitelli”, which approved the research (code 1/2017) and certified that the involvement of human participants was performed according to acceptable standards.(a)Italian version of the modified Differential Emotions Scale see : The ori(b)Pittsburgh Sleep Quality Index (PSQI ): This q(c)Mannheim Dream Questionnaire (MADRE ): This qAs for the validation study, the structure and psychometric properties of the Italian version of the mDES (both WAKE-24hr and WAKE-2wks versions) were examined through an item analysis , a Principal Components Analysis (PCA) with Varimax Rotation, a confirmatory factor analysis, and a validity and reliability Analysis . Descriptive and inferential statistics were analyzed through SPSS Statistics 19 and STATISTICA 10; validity and reliability analyses, as well as PCA, were performed by means of STATISTICA 10; confirmatory factor analysis was carried out through LISREL 8.71.p2 as a measure of effect size and using the Holm test for post-hoc analysis. A series of repeated measures ANOVAs (with 3 levels: WAKE-2wks/WAKE-24hr/Dream) was also performed to explore changes between wake and dream in all the specific emotions, using ηp2 as a measure of effect size and the Holm test  for post-hoc analysis. Moreover, in order to explore the potential predictors of dream emotions, we conducted several multiple linear regressions with each dream emotion as dependent variable and WAKE-24hr and WAKE-2wks emotions as predictors. For each significant predictor, we reported the unstandardized (b) and the standardized (β) coefficients. For both the ANOVAs and the regression models involving specific emotions, main effects were corrected using the False Discovery Rate (FDR) approach with Benjamini–Hochberg adjusted p-value, whereas post-hoc tests were corrected using the Holm approach.For the dream study, data analysis was conducted using JAMOVI 1.2.27. Descriptive data are reported as mean ± standard deviation or frequency. To assess the differences in positive and negative emotionality  experienced during wake and dream, we conducted a 2  × 3 (Condition: WAKE-2wks/WAKE-24hr/Dream) repeated measures ANOVA, reporting ηp-values were corrected using Benjamini–Hochberg adjusted p-value, whereas post-hoc tests were corrected using the Holm approach.Even though more than one WAKE-24hr mDES per participant was collected (due to the lag with which participants remembered a dream since the beginning of data collection), these analyses included only the scale referring to the 24 h preceding the dream (a single WAKE-24hr mDES per participant). Instead, the additional WAKE-24hr mDES scales  were studied in a separate analysis aimed to explore the presence of potential lag effects in the expression of waking emotions in the dream. Taking into account the different number of observations collected for each participant, we built a linear mixed model on emotion intensity scores with Valence (Positive and Negative) and Lag  as fixed factors and participant as random factor. In this case, Bonferroni was used for post-hoc comparisons. Again, p < 0.05 was considered statistically significant.A A bifactorial structure was confirmed for both mDES forms, which also showed good validity and reliability. All the results from the validation study are presented as n = 50) were 5.98 ± 2.59, indicating a mild degree of poor subjective sleep quality in our sample.Average PSQI scores  had a median of 2.50 (range 1–4), whereas affective tone had a median of 0 (from −2 = very negative to 2 = very positive), with 38% of participants reporting negatively toned dreams and 48% positively toned dreams. Finally, 58% of the sample reported to experience nightmares at least once a month, whereas the remaining 42% less than once a month.A total of 50 dream mDES and 50 WAKE-2wks mDES (one per participant) were collected. As for the WAKE-24hr version, 84 scales were collected in total (50 referring to the day immediately preceding the dream and the remaining referred to the previous days); in fact, thirty participants (60%) recalled a dream after 1 night, 6 participants (12%) after 2 nights, and the remaining 14 (28%) after 3 nights.p = 0.125, Cohens’ d = 0.22), indicating a balanced intensity of positive and negative emotionality in the dream.Scores at the Positive and Negative Affect subscales  of the DREAM mDES did not differ , with higher scores for WAKE-2wks emotions compared to WAKE-24hr and Dream  but no difference between WAKE-24hr and Dream (p = 0.467). We also observed a significant main effect of Valence , with higher scores for PA (p = 0.003), and a significant interaction Valence × Condition , whereas NA was reduced from WAKE-2wks to WAKE-24hr (p < 0.001) and increased from WAKE-24hr to Dream (p = 0.004). See also The ANOVA showed a significant main effect of Condition .The linear regression on the PA subscale showed that neither WAKE-2wks nor WAKE-24hr scores were predictive of PA experienced during the dream .The regression on NA scores was also non-significant  and Interest , with the corresponding WAKE-2wks emotions being the only significant predictors . Moreover, significant regression models emerged for Hopefulness , with the WAKE-24hr corresponding emotion as the only significant predictor  and for Pride , but no significant predictor emerged.As for specific dream emotions, the linear regression was significant for Embarrassment , with a general higher intensity for PA, no main effect of Lag  and a significant interaction Valence × Lag . Emotions were measured through a self-report instrument, the modified Differential Emotions Scale mDES ,48), whi, whi48])The validation study showed that the Italian mDES, both in its WAKE-24hr and WAKE-2wks forms, has good psychometric properties, in terms of internal validity, construct validity, and reliability. The factorial structure of the instrument was analyzed through confirmatory factor analysis which confirmed the bidimensionality of the scale, with the two factors corresponding to positive and negative emotion categories. The use of the Positive and Negative Affect subscales  thusMoreover, here we show that the mDES may be a useful and reliable tool to investigate dream emotionality. The mDES, in fact, has been very seldom used in dream research-with Sikka et al.’s work ,44,46,51It must be acknowledged here that, according to some authors ,63,64, sThe number of emotions reported by our participants is in line with several previous studies based on self-ratings of dream emotions, suggesting that most dreams are emotional, i.e., contain at least one emotion: 90.6% of laboratory dreams and 98.4% of home dreams in St-Onge et al.  and 100%As for the predominant dream valence, Negative Affect (NA) scores were slightly higher than those at the Positive Affect (PA) subscale, but this difference failed to reach significance. The fact that general emotional tone of the dream appears relatively balanced is coherent with dream literature based on self-reports, which mostly shows a more balanced ratio of positive and negative emotionality e.g., ,60,69) c,69 c60,6More specifically, the fact that Fear appears among the most frequent and most intense emotions in our sample is in line with studies finding emotions in the fear domain  to be the most frequently experienced in dreams  or stable (relative to the two weeks period). This suggests, as mentioned in the introduction, that valence differently affects the pathway of emotional expression from wake to the dream. A possible interpretation is that dream negative emotions reflect the negative emotions experienced more frequently during the general period in which the dream occurs , expressing the sleep-related regulation mechanisms proposed by several theoretical models ,15,16,17Another intriguing, complementary, hypothesis that comes to mind when looking at the general pattern of data is the existence of some sort of “day/night affective homeostasis” , with tHowever, it must be noted that our regression analyses did not yield significant results. In fact, scores at the general affect scales (PA and NA) of the previous day and previous two weeks did not predict those of the dream; similarly, predictive relationships among corresponding wake and dream emotions emerged only for three emotions. These results are consistent with those of the three other studies assessing associations between dream and waking emotions ,45,46: Ylast recalled dream, which is probably an early morning REM sleep dream. This type of dreams have been suggested to be characterized by greater emotional negativity than earlier night dreams [A couple of alternative explanations may be proposed to interpret our pattern of findings. One is that individuals could undergo some sort of social desirability effect in recognizing the experienced emotions from the scale ; in otht dreams .Another plausible hypothesis refers to the possibility that waking emotions are expressed in dreams across a different time span than those measured in our study. For instance, in analogy with data on the delayed incorporation of waking events in dreams ,22,23, eOur results should be considered in light of some limitations to be overcome in future research. First of all, our choice of not collecting dream reports did not allow us to control for several dream features, such as dream length ,79,80, wIn conclusion, this study is the first to investigate the relationships of dream emotions with those experienced during the previous waking days using the same instrument, the modified Differential Emotions Scale, which assesses a broad array of positive and negative emotions and has proved to possess good psychometric properties in a preliminary validation study. Overall, our findings highlight a discontinuity between wake and dream affect, with positive emotionality reduced in the dream and negative emotionality similar to that of the preceding two weeks but increased relative to the previous day. In the frame of recent theoretical models postulating a role of dreaming in emotion regulation processes, these results suggest that positive and negative emotions experienced during wake may undertake different but parallel sleep-related regulation pathways. Although we did not observe strong direct relationships between wake and dream emotions, these findings also suggest the intriguing hypothesis of a “day/night affective homeostasis” to be addressed in forthcoming studies. Future research assessing wake and dream emotions over longer time periods and in different kinds of samples , as well as studies conducted with experimental rather than correlational designs, could be usefully implemented to further investigate this interesting possibility.


At rest, myocardial blood flow in an area of myocardial infarction is roughly 20% that of blood flow in remote myocardium . Since mThe purpose of this study was to determine the sensitivity of resting cardiac magnetic resonance (CMR) perfusion for evaluating the presence and extent of myocardial infarction, as defined by delayed contrast-enhanced (DE) CMR.59 patients were imaged serially following acute ST-segment elevation myocardial infarction (MI) by CMR cine and DE as part of a study evaluating the ability of CMR indices to predict post-MI remodeling . We retrFor all studies with MI identified by DE, the sensitivity of resting CMR perfusion for the detection of MI was 71% (59/83). The sensitivity was higher in patients with acute infarcts  than for patients with chronic infarcts . The mean number of segments demonstrating hyperenhancement was higher than the mean number of segments demonstrating resting perfusion defects . When comparing patients with true-positive perfusion studies to those with false-negative perfusion studies, the mean hyperenhancement score was higher . Figure The sensitivity of resting magnetic resonance first-pass myocardial perfusion imaging for the detection of myocardial infarction is relatively low, and the extent of hyperenhancement is larger than the extent of perfusion defects. Sensitivity is higher for acute infarcts than for chronic infarcts, and smaller infarcts are more likely to be missed. When performing first-pass perfusion studies, delayed contrast-enhanced imaging also needs to be performed for accurate assessment of the size and extent of myocardial infarction.


Eplerenone (EP), an aldosterone antagonist, is reported to produce renal and cardiac protective effects in noncanine species. However, there are no detailed reports available on cardiovascular effects of EP in dogs. This study aimed to determine effect of EP on echocardiographic parameters, blood pressures, and biochemical variables in healthy dogs. Five healthy Beagle dogs were randomly divided and repeatedly used in each of 3 dose groups, receiving 2.5, 5, or 10 mg/kg BW EP orally q24 h for 4 wks. Serum biochemical test, blood pressure, and Doppler echocardiography measurements were performed before EP administration and at 1, 2, and 4 weeks after EP administration. Treatment with EP reduced mean blood pressure in a dose-dependent manner and significantly (but in a dose-independent manner) decreased left atrium/aorta ratio, early diastolic transmitral flow, early diastolic transmitral flow/late diastolic transmitral flow, peak velocity of early diastolic transmitral flow/peak velocity of early diastolic mitral annular motion, left ventricle and right ventricle Tei indices, stroke volume, cardiac output, and mid systole myocardial velocity gradient 1 to 4 weeks after administration. Deceleration time of early diastolic transmitral flow significantly increased after EP administration. No significant changes were observed in serum biochemical variables. The results indicated that EP might reduce preload, thereby decreasing left atrial size. In addition, reduction of left ventricular stiffness may have theoretically taken place but this could not be tested using the present study design. It is suggested that EP administration within the dose range used in this study is safe for administration to healthy dogs. Further studies are needed to explore both safety and efficacy, as well as to seek a recommended dose range of EP treatment in client-owned dogs with heart disease. Aldosterone is a steroid hormone that is synthesized in the adrenal cortex and has a role in the renin-angiotensin–aldosterone system (RAAS). It induces fluid retention via the renal mineralocorticoid receptor by reabsorbing sodium and water ions. Aldosterone has been shown to promote myocardial fibrosis in rats . MoreoveSpironolactone, an anti-aldosterone drug, has been reported to reduce the mortality rate in dogs with mitral regurgitation caused by myxomatous mitral valve disease  and in cTreatment with EP exerts renal and cardiac protective effects in rat models of heart failure treated with angiotensin II and Nω-Nitro-L-arginine methyl ester  and imprTo the best of our knowledge, no detailed reports are currently available in the veterinary literature addressing the cardiovascular and serum biochemical effects of lower-dose EP in dogs. The aim of this pilot study was, therefore, to characterize the effects of EP on key echocardiographic parameters, blood pressure, and serum biochemical variables in healthy dogs and determine its potential safety. The hypothesis of this study was that EP may lower blood pressure even at low doses and may reduce left ventricular preload and stiffness.Five healthy, adult, neutered, female Beagle dogs  were used in this study. The dogs were fed a standard commercial dry food formulated for dogs and were raised in an appropriate animal management facility. The physical and hematological examinations performed before the experiments confirmed that all dogs were healthy. The study protocol was principally based on the Guide for the Care and Use of Laboratory Animals developed by the Institute of Laboratory Animal Research of the National Research Council of Japan and approved by the Animal Research Committee of Tottori University.The five dogs were assigned to receive each of the three treatment groups. The dogs received 2.5, 5, or 10 mg/kg of EP  orally q24 h for 4 weeks. Hereafter, the groups are denoted as EP 2.5, EP 5, and EP 10. Treatments were conducted in the order of EP 2.5, EP 5, and EP 10 in 3 dogs, EP 5, EP 10, and EP 2.5 in 1 dog, and EP 10, EP 2.5, and EP 5 in 1 dog. As it has been reported that the half-life of EP in dogs is 2.21 h, and EP and its metabolites are readily excreted , the wasSample collection and serum biochemical analyses were performed as reported previously : blood  with a 5 MHz probe. Heart rate (HR) was simultaneously calculated from the preceding R-to-R interval on the electrocardiogram. By using the M-mode method, the left atrium/aorta (LA/Ao) ratio was measured from the left ventricular (LV) outflow tract view in the right parasternal long-axis view with dogs in right lateral recumbency. LV fractional shortening (FS) [E), peak velocity of late transmitral flow (A), E/A ratio, and deceleration time of early diastolic transmitral flow (DTE) were recorded in the left apical four-chamber view. In the apical five-chamber view, a pulsed-wave sample volume was placed immediately below the aortic valve. The cross-sectional area of the left ventricular outflow tract, aortic peak ejection flow velocity (AEV), and velocity time integral (VTI) were measured from this view, and stroke volume (SV) [a) from the end of the left ventricular active and late inflow to the initiation of the early and passive reinflow was measured using the left apical four-chamber view. The time (b) from the onset to the offset of the LV ejection flow was measured using the apical five-chamber view. The LV Tei index was calculated as (a − b)/b [a) of the end of the right ventricular tricuspid inflow to the initiation of reinflow in the apical four-chamber view and from the time (b) of the onset to the offset of the right ventricular ejection flow in the apical short-axis view [E′) and the peak velocity of the late diastolic mitral annular motion (A′) were measured using high frequency tissue Doppler imaging, and the ratio of E′ to A′ (E′/A′) was calculated. Furthermore, the ratio of E to E′ (E/E′) was calculated. The endomyocardial and epimyocardial velocities were measured at the posterior wall of the LV in the short-axis view, and the myocardial velocity gradient (MVG) was calculated by dividing the difference  of the distance between the two points [Echocardiographic parameters and blood pressure measurements were performed as reported previously  as folloing (FS) , LV ejecing (FS) , interveume (SV)  and carda − b)/b . Likewisxis view . By usino points . The MVGP < 0.05.All data obtained were analyzed using commercially available software . One-way analysis of variance was used to examine the time effect within each group and the treatment effect at each time point for serum biochemical, echocardiographic, and blood pressure variables. When a significant difference was detected, Tukey's test was used to compare the means. The dose-dependent relationship was analyzed by a linear regression analysis. The results are expressed as mean ± standard error. The level of significance in all tests was set at E, A, E/A, DTE, and E/E′ values after EP administration. In the EP 10 group, the E values at 1, 2, and 4 weeks after EP administration decreased significantly compared with those observed at baseline. The A value did not change significantly in response to any of the EP doses. E/A in the EP 5 and EP 10 groups decreased significantly compared with baseline date and at 2 weeks and 1 week, respectively. At 2 and 4 weeks, DTE in the EP 5 (but not in the EP 10) group increased significantly compared with that recorded at baseline. E/E′ in the EP 2.5 and EP 10 groups decreased significantly at 2–4 weeks and 1–4 weeks compared with the baseline, respectively. E/E′ in the EP 5 group did not significantly decrease after EP administration. There were no significant differences between the groups in E, A, E/A, DTE, and E/E′ values.The LV Tei index in the EP 2.5, EP 5, and EP 10 groups decreased significantly at 4 weeks, 2–4 weeks and 1–4 weeks compared with the baseline, respectively . The RV E′, A′, E′/A′, MVGs, MVGe, and MVGa. The E′ value in the EP groups did not significantly increase after EP administration. A′, E′/A′, and MVGa did not change significantly after EP administration in any of the groups. At 4 weeks, MVGs in the EP 2.5 group decreased significantly compared with that observed at baseline. MVGs in the EP 5 and 10 groups and MVGe in all EP-treated groups did not significantly change after EP administration when compared with the baseline. There were no significant differences between the groups in each variable listed in R2 = 0.4175; P=0.0093) at 4 weeks.No behavioral adverse effects were observed in any of the groups.E wave, E/A, and E/E′ in healthy dogs. A decrease in E wave, E/A, and E/E′ suggests a decrease in left atrial pressure [E′ is observed with decrease in LA pressure in dogs with mitral valve insufficiency [E, and decreased E/E′ ratio, with no apparent change in E′.The results of this study revealed that EP administration reduced the LA/Ao, pressure . A decreficiency . The chaThis study revealed that EP administration reduced CO, SV, MVGs, MBP, and DBP and tended to reduce FS and SBP in clinically normal dogs. The decrease in the LV preload is known to induce the reduction of SV via the Frank–Starling mechanism in a healthy heart. The observed decrease in diastolic blood pressure induced by EP may be due to a decrease in either CO or systemic vascular resistance or both , 31. TheE and significantly reduced E/E'. It has been reported that DTE can be prolonged with a left ventricular stiffness decrease [E extended even in the face of deduced left ventricular preload reduction. However, LV stiffness, too, was not directly investigated or otherwise quantified in the present study. The changes of these parameters might indirectly suggest the enhancement of LV diastolic function [This study revealed that EP administration significantly increased DTdecrease . Therefofunction , 28, 33.function . It has function . Althougfunction , our stufunction  and myocfunction . EP has function . TherefoIn general, a reduction in SV and CO is thought to worsen “forward” heart failure, while in congestive heart failure a reduced preload should contribute more to symptomatic relief than the potential harm brought about by the concomitant reduction of fractional shortening . Our stuDuring treatment with EP, patients/animals should be monitored for the development of hyperkalemia . HoweverThere are some limitations in this study. In our pilot study design, only five dogs were used repeatedly, and all were females. Plasma aldosterone concentrations were not measured in this study. In humans, EP has been reported to have equivalent antihypertensive effect with both SID and BID administrations . This stSimilarly, the LA/Ao ratio in the present study was based on M-mode imaging in the right parasternal long-axis view rather than on more widely accepted 2D imaging in the right parasternal short-axis view. Finally, in the present study, the MBP decreased in a dose-dependent manner. While no significant dose-dependent effects of EP were observed for any of the other quantified parameters, some echocardiographic parameters did show significant changes at the low EP dose. It is suggested that EP can initiate cardiovascular effects even at lower doses  than those  reported previously in dogs , 21. TheTo the best of the authors' knowledge, the present pilot study is the first to systematically investigate the effect of EP on key echocardiographic parameters, blood pressure, and serum biochemical variables in healthy dogs. The present study indicated that EP is likely to reduce preload and therefore reduces left atrial size and potentially left ventricular stiffness. The present results also suggest that EP administration within the dose range used in this study is safe when given to healthy dogs. Our findings should be taken into consideration when designing future research on the clinical safety and efficacy of EP in canine cardiovascular disease.


While invasive assessment of hemodynamics and testing of acute vasoreactivity in the catheterization laboratory is the gold standard for diagnosing pulmonary hypertension (PH) and pulmonary vascular disease (PVD) in children, transthoracic echocardiography (TTE) serves as the initial diagnostic tool. International guidelines suggest several key echocardiographic variables and indices for the screening studies when PH is suspected. However, due to the complex anatomy and special physiological considerations, these may not apply to patients with congenital heart disease (CHD). Misinterpretation of TTE variables can lead to delayed diagnosis and therapy, with fatal consequences, or–on the other hand-unnecessary invasive diagnostic procedures that have relevant risks, especially in the pediatric age group. We herein provide an overview of the echocardiographic workup of children and adolescents with PH with a special focus on children with CHD, such as ventricular/atrial septal defects, tetralogy of Fallot or univentricular physiology. In addition, we address the use of echocardiography as a tool to assess eligibility for exercise and sports, a major determinant of quality of life and outcome in patients with PH associated with CHD. Pulmonary hypertension (PH) associated with congenital heart disease (CHD) is a complex condition associated with increased morbidity and mortality that can affect individuals at any age ,2,3. Acc2, in addition to mPAP > 20 mm Hg and PAWP or LVEDP ≤ 15 mm Hg. Thus, PAH with only slightly elevated PVR index is neither synonymous nor indicative of PVD in patients with CHD ), using continuous wave (CW)-Doppler to assess the TRV, describes the relationship of TR and right ventricular systolic pressure (RVSP) as a surrogate of sPAP ,5737,57]Besides PAAT alone, the ratio of PAAT and RV ejection time (RVET) has been shown to be reduced in adults and children with PH and to highly correlate with mPAP ,64. EspeFor estimation of PVR, the RVOT VTI can be obtained from PSAX by placing a PW Doppler sample in the RVOT just proximal to the pulmonary valve . Age-relThe systolic (S) to diastolic (D) duration ratio reflects the global RV function. By using TR duration from Doppler flow, durations of S and D are measured in the apical four-chamber view B. The duIn children with HLHS, S/D duration ratios after the Norwood procedure  were significantly higher compared to those after Glenn- or Fontan-Procedure . However, S/D durations after Glenn-/Fontan-Procedure were demonstrated to be significantly higher as compared to healthy controls . Moreoveculation ,79.TAPSE, usually measured in M-Mode in the apical four-chamber view, assesses the longitudinal excursion of the tricuspid annulus towards the apex during systole A 80]. B. B80]. BContemporary echocardiographic assessment of RV function in patients with PH requires a multiparametric approach that includes TAPSE to avoid overreliance on a single parameter. For example, TAPSE/sPAP ratio values have been shown to inversely correlate to New York Heart Association functional class (NYHA FC) and thus might be helpful in predicting outcomes in children and adults ,87,88,89In critically ill patients following cardiac surgery, the assessment of TAPSE in the apical four-chamber view is often hampered by extensive wound dressings . ReferenImportantly, it should be noted that TAPSE is preserved for a long time in the disease process, especially in younger children, despite very high PAP, and as such, TAPSE is a typical echocardiographic variable that when used as a single surrogate, can lead to a gross misinterpretation of systolic function.The RV FAC, recommended by recent guidelines for the evaluation of RV systolic function ,2,3, refFAC use for assessing RV systolic function is limited by several factors: FAC is dependent on preload and has been shown to be less reproducible than TAPSE ,99,100. Tissue Doppler imaging (TDI) allows for the assessment of systolic and diastolic ventricular function by measuring myocardial velocities by PW-Doppler in the apical four-chamber view ,104. TheEspecially beneficial in patients with operated PH-CHD, TDI is independent of chamber geometry, which permits its use in any chamber configuration . ReducedIn adult patients with RV pressure overload due to severe PH, RV tricuspid S’ was demonstrated to be lower as compared to patients with RV volume overload due to, e.g., an ASD , in which elevated tricuspid S’ and lower tricuspid E’ values were shown ,112. AccStrain measurements provide substantial information on RV and LV global and regional function. The technique is angle independent and less load-dependent than classic parameters of ventricular function. ,115. ThiIn adults with PAH, RV global longitudinal peak systolic strain and strain rate have been shown to be lower with varying degrees of PAH than controls . LikewisIn both adults and children with PH, RV diastolic dysfunction and elevated RAP are associated with increased mortality ,99,129. In children with PH, lower E’ velocities have been shown as compared to controls . The triRA strain measurements are also useful indicators of RV diastolic function. In adults and in children with PH, all phases of atrial function  have been shown to be impaired, which likely reflects RV failure and overload ,133. WorVVI refers to the impact of alterations in function, filling, pressure and volume related changes in geometry and synchrony that one ventricle shows in response to pathologic changes that primarily affect the other ventricle ,25,137. The end-systolic LV eccentricity index (LVesEI), measured in the PSAX, is defined as the ratio of the minor axis of the LV parallel to the septum divided by the minor axis perpendicular to the septum and is used to evaluate the LV compression for hemodynamic assessment in PH patients  37,141],14137,14However, the maximal leftward septal shift in PH often occurs at the time of mitral valve opening (early LV diastole) . In accoBy using strain measurements, a negative impact of RV dilation on LV circumferential deformation, but not on longitudinal or radial deformation, has been demonstrated . FurtherHowever, the RV/LV ratio, the LVesEI as well as the LVpsEIM should be interpreted cautiously, especially in patients with PH/PAH after surgical repair of CHD as the structure and shape of the IVS may be affected by the procedure  . FurtherLV systolic function can be estimated by LVEF determination using the biplane Simpson formula. In pediatric patients with severe PH, a decreased LVEF has been shown to be associated with an increasing ratio of sPAP/sSAP and an increasing PVRi . Althoug2 × 3.14 × VTI (LVOT) × HR [Severe septal shift may lead to obstruction of the LV-mid cavity or LVOT and therefore to decreased CO. CO can be estimated by the following equation: CO = (LVOT diameter/2)OT) × HR . The LVOOT) × HR .The differentiation between normal and abnormal LV diastolic function is challenging as diastolic measurements are heavily influenced by age, heart rate and preload, among other factors . LV diasThe mitral Doppler inflow is assessed in the apical four-chamber view with the curser placed across the mitral valve just inside the LV . Early LBy TDI measurements, mitral S’, E’, and A’ velocities can be determined; however, in pediatric patients, normal values and z-scores should be used ,157. The2 may indicate LV diastolic dysfunction in adults [For LA pressure estimation, the assessment of the LA maximum volume index from the apical four-chamber view at end-systole should be preferred over measurements of linear dimensions ,132. A Ln adults . An incrn adults . Bowing n adults . In chiln adults ,144. Impn adults ,144.After percutaneous ASD device closure, mitral E wave and mitral E/E’ ratio values significantly increased, which indicated elevated LV filling pressures in a small cohort of adult patients . In contEchocardiographic evidence of systolic and diastolic ventricular dysfunction has also been demonstrated by TDI measurements in patients with Fontan physiology, with TDI velocities being lower in both left and right systemic ventricles as compared to normal age-related values. However, morphologic RVs show more severely depressed TDI values than LVs in patients with single-ventricle physiologies . In chilIn addition, a higher LV free wall E/E’ ratio (≥12) is associated with a reduced peak oxygen uptake (VO2peak) in adult patients after Fontan palliation .Commonly, echocardiography is performed at rest and can thus only partially aid in understanding the pathophysiology of the often debilitating exercise intolerance experienced by patients suffering from PAH and RV dysfunction . While eThe assessment of RV function during exercise stress (ventricular reserve) has been used in adult PAH  to explaA pathophysiological study questioned the hypothesis that PAP changes indeed indicated RV contractility changes  and concParameters such as PW TDI and 2-D strain can describe myocardial exercise reserve, and normal reference values for children exist ,169,170.In PH-CHD, differentiation between an elevated PAP with or without PVD and appropriate etiologic classification of disease entities represent critical prerequisites for optimal management. The new WSPH classification (2018) may assign a patient to more than one PH group . Screening for the presence of PH during routine TTE should be performed in every CHD patient as PH/PAH may develop even after surgical repair, and this review highlights the most useful and predictive echocardiographic parameters and their specific virtue. This review also describes that many echocardiographic variables and indices which are recommended for screening of (suspected) PH in international guidelines do not apply to patients with CHD, and the rationale for specific echocardiographic variables to monitor PH in CHD are described. In addition, as exercise capacity represents a major potential outcome variable in children with PH, this review provides an overview of the use of exercise stress echocardiography as a novel tool to monitor myocardial exercise performance.


The 2016 guidelines for left ventricular diastolic dysfunction diagnosis has been simplified from previous versions; however, multiparametric diagnosis approach still exists indeterminate left ventricular diastolic dysfunction category. Left atrial (LA) strain was recently found useful to predict elevated left ventricular (LV) filling pressures noninvasively. This study aimed to (1) analyze the diagnostic value of LA strain for noninvasive assessment of LV filling pressures in patients with stable coronary artery disease (CAD) with preserved LV ejection fraction (LVEF), using invasive hemodynamic assessment as the gold standard, and (2) explore whether LA strain combined with conventional diastolic parameters could detect elevated LV filling pressures alone.Sixty-four patients with stable CAD having LVEF > 50% and 30 healthy controls were enrolled. Two-dimensional speckle-tracking echocardiography was used to measure LA strain during the reservoir (LASr), conduit, and contraction phases. LV end-diastolic pressure (LVEDP), as a surrogate for LV filling pressures, was invasively obtained by left heart catheterization. Logistic regression was used to calculate the odds ratio to predict LV filling pressures. Pearson’s correlation was used to analyze associations between echocardiographic parameters and LVEDP. The area under the receiver-operating characteristic curve was calculated to determine the capability of the echocardiographic parameters to detect elevated LVEDP. Inter-technique agreement was analyzed by contingency tables and tested by kappa statistics.LASr and the ratio of early-diastolic transmitral flow velocity (E) to tissue Doppler early-diastolic septal mitral annular velocity  significantly predicted elevated LV filling pressures. LASr was combined with E/E′septal to generate a novel parameter . LASr/E/E′septal had the best predictive ability of elevated LV filling pressures. LVEDP was negatively correlated with LASr and LASr/E/E′septal but positively correlated with E/E′septal. The area under the receiver-operating characteristic curve of LASr/E/E′septal was higher than that of LASr alone (0.83 vs. 0.75), better than all conventional LV diastolic parameters. Inter-technique agreement analysis showed that LASr/E/E′septal had good agreement with the invasive LVEDP measurement, better than the 2016 guideline (kappa = 0.63 vs. 0.25).LASr provided additive diagnostic value for the noninvasive assessment of LV filling pressures. LASr/E/E′septal had the potential to be a better single noninvasive index to predict elevated LV filling pressures in patients with stable CAD and preserved LVEF. The American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) 2016 guideline algorithms for left ventricular diastolic dysfunction (LVDD) diagnosis are simpler than previous versions, making clinical use more convenient. The latest guideline, however, still cannot solve the diagnostic quandary of “indeterminate” status for patients whose data do not neatly fulfill the algorithms . The resRecent studies have shown that abnormalities in the left atrium have an important effect on the pathophysiology and disease progression of LVDD and heart failure with preserved ejection fraction (HFpEF) –14. MoreHowever, in patients with CAD with preserved LV ejection fraction (LVEF), the role of LA strain when assessing LV filling pressures is unknown. Whether combining LA strain with conventional diastolic parameters could be a better single noninvasive method of predicting LVDD needs to be explored and compared with invasive hemodynamic data.The study population included 64 patients treated at Fuwai Hospital from October 2013 to July 2014 for stable CAD. The patients were in sinus rhythm with normal resting wall motion and preserved LVEF (> 50%) having cardiac symptoms such as angina, ischemic-type chest pain, or other symptoms suggestive of myocardial ischemia. Thirty sex- and age-matched healthy controls with good acoustic windows were enrolled. All patients underwent left ventriculography and coronary angiography. Cardiac catheterization and echocardiography were performed on the same day (within 24 h). CAD was defined as > 50% luminal stenosis in one or more major epicardial vessels by visual assessment. The exclusion criteria were as follows: (1) patients with an LVEF ≤50%, including unstable conditions such as cardiac shock and ventricular aneurysm; (2) old myocardial infarction (within the past 3 months) or with distinct regional wall motion abnormalities at rest; (3) severe aortic or mitral disease; (4) atrial fibrillation, flutter, or ventricular-paced rhythm; and (5) hypermobile interatrial septum or interatrial septal aneurysm. The following data were gathered: clinical baseline characteristics, parameters of conventional echocardiography and two-dimensional speckle-tracking echocardiography (2D-STE), and hemodynamic data during left heart catheterization.3 − (LVEDd)3] + 0.6}, where LVEDd is LV end-diastolic diameter, PWTd is end-diastolic posterior wall thickness, and SWTd is end-diastolic septal wall thickness. LV mass was then indexed for body surface area to generate the LV mass index (LVMI). Peak early-diastolic (E) and peak late-diastolic (A) transmitral velocities, the E/A ratio, and the deceleration time of the E wave were measured from the apical four-chamber view by pulsed Doppler echocardiography. Peak velocity of the tricuspid regurgitant jet was determined by continuous-wave Doppler. Peak early-diastolic myocardial velocity (E′) was measured from the apical four-chamber view by tissue Doppler echocardiography, at the levels of the basal portion of the septal and lateral mitral annuli, to generate E′septal and E′lateral, respectively, and the mean early-diastolic myocardial velocity (E′mean) was calculated. The ratio of early-diastolic transmitral flow velocity to tissue Doppler early-diastolic septal mitral annular velocity , the ratio of early-diastolic transmitral flow velocity to tissue Doppler early-diastolic lateral mitral annular velocity , and the ratio of early-diastolic transmitral flow velocity to tissue Doppler mean early-diastolic myocardial velocity (E/E′mean) were also calculated. Mitral regurgitation severity was assessed using the Doppler quantitative technique, and according to the ASE guideline [2 (using the biplane Simpson method); and (4) tricuspid regurgitation (TR) peak velocity >  2.8 m/s. Patients were diagnosed with LVDD when > 50% of the aforementioned criteria were positive and normal LV diastolic function when < 50% of these criteria were positive. In addition, when only 50% of the criteria were positive, patients were diagnosed as having indeterminate LV diastolic function. The normal reference values of other diastolic function parameters refer to the Normal Reference Ranges for Echocardiography (NORRE) Study [All conventional transthoracic echocardiographic measurements were performed at rest in the left lateral decubitus position using the Vivid E9 ultrasound system . Digital loops were stored and analyzed offline using EchoPAC clinical workstation software, version 202 . Measurements were performed on four consecutive heartbeats, and the average of three measurements was taken. Apical four- and two- chamber views were used to analyze the LV and LA volumes. LV end-systolic and -diastolic volume and ejection fraction (EF) were assessed by the biplane Simpson method. LA maximal volume, LA minimal volume, and LA volume at the onset time of the P wave were also measured by the biplane Simpson method. LA maximal volume was divided by the body surface area to obtain the LA maximal volume index (LAVI). The volumetric parameters of LA systolic function were calculated as follows : LA emptuideline . Conventuideline : (1) sep2D-STE image acquisition using the Vivid E9 ultrasound system  was performed with apical four-, three-, and two-chamber views to achieve optimal imaging quality for subsequent analyses. EchoPAC software was used to trace the LA endocardial border in both the four- and two- chamber views  curve (AUC) was calculated to determine the capability of the echocardiographic parameters to detect elevated LVEDP [Continuous variables were presented as the mean ± standard deviation and were analyzed with an independent ed LVEDP . ContingReproducibility was assessed by Bland-Altman plots, intraclass correlation coefficients, and the calculation of the absolute differences between two measurements divided by the mean, which were expressed as percentages.P-values of < 0.05 were considered to indicate statistical significance.Analyses were performed using SPSS, version 25.0 , MedCalc, version 19.0.5 , and GraphPad Prism 8 . Two-tailed Sixty patients with stable CAD and preserved LVEF were included in this study. Four patients with poor image quality in more than one LA segment were excluded (feasibility 93.8%). The control group comprised 30 age- and sex-matched healthy participants. Demographic and clinical characteristics are presented in Table The mean age of the 60 patients with CAD was 56 ± 9 years, and most (48 patients) were men. Overall, 30 patients had diabetes mellitus, 39 had hypertension, 53 had dyslipidemia, and 26 had a prior myocardial infarct. On coronary angiography, coronary artery diameter stenosis > 50% was present in a single vessel in 16 (26.7%) patients, and two or three (multiple) vessels in 44 (73.3%) patients. The location of the culprit lesion was the left main coronary artery in eight (13.3%) patients, the left anterior descending coronary artery in 54 (90.0%) patients, the left circumflex coronary artery in 40 (66.7%) patients, and the right coronary artery in 38 (63.3%) patients. The types of coronary dominance were right, left, and balanced in 51 (85.0%), five (8.3%), and four (6.7%) patients, respectively. Compared with the control group, the CAD group had higher systolic and diastolic blood pressures. Other baseline characteristics did not significantly differ between these two groups (Table n = 27) and group II . No significant differences were found between group I and group II in terms of age, gender, blood pressures, medical history, medication, or coronary angiography findings , and E/E′septal  (Table P = 0.000) became the only parameter to significantly predict elevated LV filling pressures.In univariate logistic regression analysis, the variables that significantly predicted elevated LV filling pressures included LASr, LASct, LAVI, E′septal, E/E′septal, and E/E′mean. LAScd, LVGLS, LAEF, and LAEF-active did not show significant predictive value in detecting LVDD Table . In multr = 0.48, P < 0.01) and negatively correlated with LASr  and LASr/E/E′septal   Fig. .Fig. 2CROC curve analysis showed that LASr could predict elevated LVEDP in patients with CAD and preserved LVEF , and a cut-off value of LASr < 24.7% was able to most accurately identify patients with LVEDP > 15 mmHg. However, LASr/E/E′septal was superior to LASr alone, with an AUC of 0.83  than LASr, showing good agreement with the invasive technique  was a better stand-alone parameter to predict elevated LV filling pressures in patients with stable CAD who have preserved LVEF.Our findings demonstrated that LASr (AUC = 0.75) was more beneficial in predicting elevated LVEDP and detecting LVDD than all the above mentioned conventional parameters except E/E′septal (AUC = 0.76). However, when countered with clinical situations in which the acquisition of Doppler parameters is complicated or the results are ambiguous, LASr has advantages over E/E′septal in the evaluation of LVDD. The results of our research were consistent with several previous studies, which indicated that LA reservoir strain decreased as LV diastolic dysfunction worsened  and provLA strain reflects the LV diastolic function for the following reasons. In the early stages of LVDD, as LV pressures and/or stiffness increase, the left atrium may compensate for higher LV pressures by contracting, but prolonged higher LV pressures and dysfunction may cause LA dilatation , 30. SevNormalizing LA reservoir strain to the estimated filling pressure index  further improved the discrimination ability (AUC = 0.83) of elevated LV filling pressures with relatively high sensitivity (87.9%) and specificity (74.1%) in patients with stable CAD who had preserved LVEF. LASr/E/E′septal was comprised of the best LA strain parameter and a preferable estimated LV filling pressures parameter, revealing not only the LV function affected by LV filling pressures but also the LA compliance influenced by LV diastolic function, which was a more comprehensive index in detecting elevated LV filling pressures. In a recent study, Reddy et al. found that LA compliance  may be the single best echocardiographic correlate of elevated filling pressures either at rest or during exertion in patients with preserved LVEF , and ourWhen the 2016 guideline algorithms were used to diagnose LVDD, 20 of 60 patients (33.3%) in our study were categorized as “indeterminate” status. Among the 20 patients with indeterminate results, LASr discriminated the filling pressures status in agreement with invasive measurements in 15 patients (75.0%), while LASr/E/E′septal correctly determined the status in 17 patients (85.0%). The findings suggested that LASr and LASr/E/E′septal added great complementary diagnostic value to the current guideline, particularly in patients diagnosed with “indeterminate diastolic function”. Meanwhile, LASr and LASr/E/E′septal showed substantial or good agreement with the invasive technique , significantly better than that of the 2016 guideline (kappa = 0.25). Prior studies demonstrated that in the early stages of diastolic dysfunction, LVEDP is the only abnormally elevated pressure , while mean pulmonary capillary wedge pressure and LA pressure remain normal at this time . HoweverLASr provided additional value in predicting elevated LV filling pressures in patients with stable CAD and preserved EF in comparison with conventional echocardiographic parameters in the 2016 guideline, especially when encountered with “indeterminate diastolic dysfunction” or clinical situations in which the acquisition of Doppler parameters is difficult, such as lack of or incomplete tricuspid regurgitation jet, tachycardia obscuring mitral annular tissue Doppler tracing and so on. Furthermore, LA reservoir strain combined with E/E'septal  proved to be a better noninvasive parameter to predict elevated LV filling pressures and identify LVDD earlier and more accurately in patients with stable CAD and preserved EF. However, the routine clinical use of LV filling pressure assessment by LASr/ E/E’septal alone needs further validation in larger samples. In addition, further research is required to explore how best to incorporate LASr and LASr/E/E′septal into multiparametric diagnostic models for CAD patients with preserved LVEF, and to validate the optimal cutoff value for these parameters to differentiate LVDD from the normal.Several limitations of our research should be noted. First, the sample size in our study was relatively small. Thus, further multicenter studies with large samples are necessary to confirm our preliminary findings. Second, patients with atrial fibrillation or other severe arrhythmia were excluded from this study; the populations comprised patients with CAD with preserved LVEF. Thus, the present findings may be only generalizable to patients with sinus rhythm with intermediate to high probability of LVDD and preserved LVEF. Third, we used the average of the four- and two-chamber views to analyze LA strain, rather than the four-chamber view alone as recommended . HoweverLASr could provide additional value in predicting elevated LV filling pressures in patients with stable CAD who have preserved EF in comparison with the conventional echocardiographic parameters of the 2016 guideline. LASr/E/E′septal, superior to LASr, had the potential to be a better stand-alone echocardiographic parameter to identify elevated LV filling pressures and discriminate LVDD earlier and more accurately in patients with stable CAD and preserved EF.Additional file 1: Table S1. LA Strain Variables of four- and two-chamber views vs. four-chamber view alone. Table S2. Logistic Regression Analysis of Variables Indicating Left Ventricular Diastolic Dysfunction . Table S3. Receiver Operating Characteristic Curve Analysis .Additional file 2: Figure S1. Bland-Altman analysis for intra-observer and inter-observer variabilities for LA strain measurements of four-chamber view alone.


To investigate the relationships between global and sectoral macular vascular microcirculation parameters in the ganglion cell-inner plexiform layer (GCIPL) assessed by optical coherence tomography angiography (OCTA), and global and sectoral visual field (VF) central mean sensitivity (CMS) assessed by standard automated perimetry.Fifty-four eyes with open angle glaucoma were scanned using a swept-source OCTA  and macular vascular microcirculation was measured by calculating the overall flux and vessel area density (VAD) over the entire 6mm x 6mm area, excluding large retinal vessels. Central 10-degree VF CMS was calculated based on 24–2 VF. Pearson correlation was used to investigate the correlation between global and sectoral OCTA parameters and global and sectoral VF CMS.Both global GCIPL flux and VAD were significantly correlated with VF CMS (p<0.001). For the sectoral analysis, sectoral VAD was significantly correlated with sectoral VF CMS in all comparisons except for the inferonasal VF CMS with supero-temporal (ST) GCIPL VAD (p = 0.097). Although highest correlation was observed for both ST VF CMS with inferior GCIPL VAD and infero-temporal VF CMS with superior GCIPL VAD , there was no significant difference in correlation when compared to the global VAD and other sectors' correlation coefficients (p≥ 0.091), except for the ST GCIPL VAD (p = 0.001).Global and sectoral macular vascular microcirculation in the GCIPL, as determined by OCTA, was significantly correlated with global and sectoral VF CMS in glaucomatous patients. OCTA can aid in the understanding of the structure-function relationships of the macular region. Glaucoma is a leading cause of irreversible blindness and diagnosis is frequently delayed due to asymptomatic disease progression until relatively late stages . ProjectAmong many risk factors for the development of glaucoma, only intraocular pressure (IOP) has been found to be modifiable . Other rAutomated static perimetry is the standard test used for assessing peripheral retinal sensitivity in patients with glaucoma. The purpose of the present study is to investigate the relationships between global and sectoral VF central (10 degree) mean sensitivity (CMS), and global and sectoral macular vascular microcirculation parameters in the ganglion cell-inner plexiform layer. We hypothesized that global and sectoral macular vascular microcirculation detected by OCTA correlates with disease severity and corresponding sectoral VF central mean sensitivity measurements in glaucomatous eyes and sought to evaluate whether any sector has more significant correlation compared to global or other sectors correlations.This study was approved by the Institutional Review Board of the University of Washington (UW) and informed consent was obtained from all subjects before imaging. This study followed the tenets of the Declaration of Helsinki and was conducted in compliance with the Health Insurance Portability and Accountability Act.Patients with diagnosis of open-angle glaucoma were prospectively enrolled at the UW Medicine Eye Institute. Inclusion criteria were defined as best-corrected visual acuity of 20/40 or better and refractive error between -6.0 and +3.0 D spherical equivalent. Exclusion criteria were defined as significant media opacity preventing high-quality imaging, any ocular disease other than glaucoma or cataract, and previous intraocular surgeries other than uncomplicated glaucoma or cataract surgery. Diagnosis of open-angle glaucoma was based on (1) optic disc rim defect (thinning or notching) or RNFL defect visible through either slit-lamp biomicroscopy or optic coherence tomography (OCT) scan; and (2) glaucomatous VF loss. Each subject received a comprehensive ophthalmologic exam and underwent a VF exam to determine mean deviation (MD) and pattern standard deviation (PSD). All VFs were performed on a Humphrey Field Analyzer II , and only reliable tests were included . Patients were classified into stages based on HVF MD value: mild stage has MD no worse than 6.00 dB; moderate stage has MD worse than -6.00 dB but no worse than -12.00 dB; severe stage has MD worse than -12.00 dB. Visual field central mean sensitivity  was calculated by averaging the anti-log absolute sensitivity values within the central 10 degrees (12 tested points) area . One eyeBlood pressure (BP) was measured in a seated position using the Welch Allyn  automatic BP monitor. The BP was measured once at the same visit immediately after the OCTA scan to calculate mean ocular perfusion pressure (MOPP). MOPP was defined as 2/3 , where mean arterial pressure = diastolic BP + 1/3(systolic BP–diastolic BP).en face images were generated using maximum projection. Macular vascular microcirculation was then measured as previously described by calculating the overall flux, vessel area density (VAD), vessel diameter index (VDI), vessel skeleton density (VSD), vessel perimeter index (VPI) and vessel complexity index (VCI) over the entire 6mm x 6mm area excluding large retinal vessels [All subjects were scanned centered at the foveola using swept-source OCTA , characterized by a central wavelength of 1050 nm, a bandwidth of 100 nm, and a 100 kHz scanning rate. Each scan consisted of 500 A-scans within one B-scan and 500 B-scan clusters (2 repeats at each transverse location) covering a 6 mm x 6 mm scanning area. The scanning depth was 3.0 mm in tissue with 1536 sampling pixels. Blood flow signals were extracted using a complex optical microangiography (OMAG) method and exported from the Plex Elite device. A semi-automatic retinal layer segmentation program was applied to the structural OCT images to precisely separate the GCIPL from the outer boundary of the nerve fiber layer to the outer boundary of the inner plexiform layer . Macular vessels . Measure vessels . In brieSample size was calculated using G*Power 3.1 ; with p Pearson correlation was used to investigate the correlation between global and sectoral OCTA parameters and global and sectoral VF CMS adapted from the structure-function correspondence map suggested by Garway-Heath et al. . The supWe included fifty-four eyes from 54 enrolled subjects diagnosed with open-angle glaucoma . BaselinGlobal GCIPL thickness and global OCTA parameters were significantly correlated to functional and structural clinical measurements, except for global GCIPL thickness and VF PSD (p = 0.109) .All global GCIPL OCTA parameters  were significantly correlated with VF CMS (p<0.001), except for global GCIPL vessel diameter and global VF CMS (p = 0.251) .For the sectoral analysis, sectoral VAD was significantly correlated with sectoral VF CMS in all comparisons, except for the ST GCIPL VAD and IN VF CMS (p = 0.097) . AlthougSectoral analysis for the other OCTA parameters also showed statistically significant correlations between VSD and VPI in all sectors (p < 0.001), except for the ST GCIPL parameters and IN VF CMS (p = 0.097). Vessel diameter and VCI were found to be insignificantly correlated with VF CMS in all sectoral analysis parameters except for SN GCIPL and IT VF CMS .Evaluating the strength of structural and functional associations in glaucoma is essential to improve our ability to detect the presence and progression of glaucomatous damage and can have clinical implications, as the use of the stronger region could provide better detection and follow up in glaucoma for patients who may present with an early stage of macular VF defects. In the present study, we investigated macular vascular microcirculation in the GCIPL among eyes with open-angle glaucoma with different severity stages using OCTA and VF assessment methods. Global macular vascular microcirculation in the GCIPL, as determined by OCTA, was significantly correlated with global VF CMS in glaucomatous patients. Sectoral macular vascular microcirculation was also significantly correlated with sectoral VF CMS in all sectors except for the ST GCIPL and IN VF CMS. Other parameters such as vessel diameter and VCI were not significantly correlated with functional changes.Shin et al.  studied Prior studies have used 3 x 3mm OCTA scans to study the macular region in eyes with glaucoma. Yarmohammadi et al.  investigWe chose to study the sectoral OCTA parameters to better understand the relationship of blood flow and glaucoma damage. The sectoral VF CMS was adapted from the structure-function correspondence map suggested by Garway-Heath et al.  Fig 1)..Fig 1). The structure–function relationship in glaucoma has been commonly reported using a simple linear regression model –34, but Our study has some limitations. We obtained our VF CMS by averaging the 12 central points of the 24–2 HVF. Although 24 degree VF testing is routinely used in glaucoma patients, 10 degree VF testing could have increased the sensitivity to detect parafoveal VF defects . Also, aIn conclusion, we found significant correlations between global and sectoral macular vascular microcirculation in the GCIPL and global and sectoral VF CMS in glaucomatous patients. To the best of our knowledge, this study is the first to compare GCIPL structure and different VF deficits using scanning patterns determined by an OCTA device. These results show that OCTA may aid macular structure-function relationship studies in glaucoma patients, though further research is warranted.S1 File(XLSX)Click here for additional data file.


To investigate the relationship between fragmented QRS (fQRS) quantified by a new method and myocardial fibrosis (MF) and the diagnostic value of quantitative fQRS (Q-fQRS) to detect MF in hypertrophic obstructive cardiomyopathy (HOCM) patients based on histological validation.We performed a retrospective study that included 69 patients with HOCM who underwent ventricular septal surgery. Nine individuals who died from accidents were studied as a control reference for the histological parameters. Septal myocardium samples were subjected to Masson’s trichrome staining to quantify the collagen volume fraction (CVF). An fQRS pattern was defined as the presence of additional R waves or RSR’, evidenced by notched R or S wave on electrocardiography (ECG). The Q-fQRS was quantified as the total amount of deflections in the QRS complex in all 12 routine ECG leads together. Cardiac magnetic resonance imaging was conducted, and late gadolinium enhancement (LGE) was measured at 2, 4, 6 and 8 standard deviations (SDs).P < 0.001; P = 0.040). Q-fQRS was correlated with CVF , and Q-fQRS showed the best correlation with LGE measured at 8 SD . Multivariate regression analyses revealed that Q-fQRS was independently associated with the extent of CVF in HOCM patients after adjusting for age, sex, body surface area and the extent of LGE at 6 SD (P < 0.001). When the patients were divided into subgroups with normal CVF or high CVF according to the CVF in controls, Q-fQRS and LGE at 6SD showed similar diagnostic value in detecting patients with high CVF, with sensitivities of 66.7% vs 68.6%, specificities of 76.7% vs 72.4%, and accuracies of 71% vs 70.3%.Of the 69 patients, fQRS was documented in 38 (55.1%) patients, the mean number of leads with fQRS was 3.7 ± 1.6, and the mean Q-fQRS was 17 ± 7.2. Compared with HOCM patients without fQRS, HOCM patients with fQRS had a higher CVF and more LGE at 6 SD (HOCM patients with fQRS showed more extensive MF. Q-fQRS was an independent predictor for MF and had a good diagnostic value, with a sensitivity of 66.7% and specificity of 76.7%, in identifying patients with higher fibrotic burden. Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease that is characterized as myocardial fibrosis (MF) . HCM patLate gadolinium enhancement (LGE) is a standard approach for the assessment of MF because collagen deposition and excessive retention of gadolinium lead to enhancement on CMR images . HoweverSixty-nine consecutive HOCM patients with symptomatic left ventricular (LV) outflow tract obstruction who underwent surgical myectomy at Fuwai hospital,Beijing between 2015 and 2020 were retrospectively studied. All patients underwent a detailed cardiovascular evaluation, including medical history, clinical examination, 12-lead ECG, and CMR.HCM was diagnosed by the criteria mentioned previously ..LV outfControl myocardium from the LV septal wall was collected at autopsy of 9 individuals  who died from accidents, showing no signs of macroscopic or microscopic cardiac lesions.A standard 12-lead ECG  was recorded in the supine position during quiet respiration before the surgeries. The fQRS was defined as previously described ,as folloTransthoracic echocardiography was performed by an experienced cardio-sonographer using the Phillips iE33 Color Doppler Ultrasound System . M-mode, twodimensional, and pulsed and continuous-wave Doppler studies were utilized in the standard evaluation according to the guidelines of the American Society of Echocardiography . All patCMR imaging was performed using a 1.5-T speed clinical scanner  before ventricular septal myectomy. All images were acquired with an electrocardiographically gated breath-hold technique.To evaluate functional parameters, electrocardiographic gating cine images were then acquired using a segmented, balanced, steady-state-free precession sequence. The images were acquired during multiple short breath holds (8–15 s). After scout images, cine imaging was performed in four chamber, three-chamber and two-chamber long- and short axis views with the following protocol: 6-mm-thick sections with a 2-mm gap between sections, repetition time, 2.7 ms; eho time, 1.2 ms; 70° flip angle; temporal resolution, 40 ms; field of view, 360 × 315 mm2; matrix, 192 × 162 pixels; pixel size, 1.9 × 1.3;slice thickness, 6 mm.All CMR images were analyzed using standard ventricular analysis software . For all patients, wall thickness at the septal, posterior and LV end-diastolic dimensions were all determined in the short-axis view (at the midpapillary level). Epicardial and endocardial borders of the LV myocardium were manually traced during the whole cardiac phase on each cine short-axis image to obtain LV and RV end-diastolic and end-systolic volumes, ejection fractions, and myocardial mass. Myocardial mass was calculated by multiplying the volume of the myocardium calculated at end-diastole by the specific gravity of the myocardium (1.05 g/ml). The end-diastolic volume index, end-systolic volume index, and mass index were indexed to body surface area. Late Gadolinium Enhanced (LGE) images were obtained 10–15 min after injection of 0.2 mmol/Kg gadolinium-DPTA.The extent of scarred myocardium was determined automatically by computer counting of all hyperenhanced pixels in the myocardium on each of the shortaxis images. Hyperenhanced pixels resembling LGE were defined as those with image intensities of 2SD, 4SD, 6SD, and 8SD above the mean of image intensities in a remote myocardial region in the same image. A percentage of LGE was then generated by the ratio of total LGE mass to total LV mass.We applied extended septal myectomy evolving from the classic Morrow procedure. The hypertrophic ventricular septal leading to systolic anterior motion of the anterior mitral valve and LVOT obstruction was resected. The resection range in the long-axis direction started from approximately 4 mm below the aortic ring to the apex of the left ventricle beyond the bases of the papillary muscles. In the shortaxis direction, the myectomy started rightward to the nadir of the right aortic cusp and to the left and terminated near the mitral anterior commissure. Part of the LV anterior free wall detached to the ventricular septal causing LVOT narrowing may also need to be resected. Furthermore, the anomalous chordal attachments between the mitral valve leaflflets or papillary muscle and the ventricular septal were also excised. Additional surgery was performed based on expert consensus among the experienced cardiac surgeons. If intraoperative transoesophageal echocardiography detected a postoperative LVOT gradient > 30 mmHg or more-than-moderate mitral valve regurgitation after weaning from cardiopulmonary bypass, reoperation was required.The septal myocardium samples were immediately fixed in 10% buffered formalin and embedded in paraffin. The samples were sectioned and stained with Masson’s trichrome staining for evaluating MF. Four images of every section were acquired with a projection microscope  or median and interquartile range according to their distribution. Categorical variables were presented as percentage frequency. Differences between groups were compared with the use of the Student t test (for parametric variables) and Mann–Whitney test (for nonparametric variables) for continuous variables. Categorical variables were compared with chi-square tests or Fisher’s exact chi-square tests. The Spearman’s correlation coefficient method was utilized to test for association between continuous variables. Patients were categorized in 2 subgroups according to values of CVF within  and above (subgroup with high CVF) the upper limit of normality . Receiver operating characteristic (ROC) analysis was plotted and the accuracy of the ROC curve was determined by measuring the area underneath it (AUC). Sensitivity, specifificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for the presence of fQRS were defined as previously reported . MultivaSixty-nine HOCM patients who underwent ventricular septal surgery were included, and LGE was assessed in 64 patients. Among the HOCM patients, the mean age was 46.1 ± 14.4 years; 43 (62.3%) were male. fQRS was documented in 38 (55.1%) patients. A representative ECG with fQRS is presented in Fig. P > 0.05). The extent of LGE at 6SD was higher in patients with fQRS than those without fQRS . The baseline characteristics are listed in Table The LV mass index, septal thickness, LV end-diastole volume index, LV ejection fraction were all comparable between HOCM patients with and without fQRS . The mean CVF was higher in patients with HOCM than in controls , and 39 patients exhibited high CVF values [subgroup with high CVF 10.48% (7.16–13.33%)]. In the ROC analysis for the identification of patients with high CVF, the AUC, sensitivity and specificity of Q-fQRS, the number of leads showing fQRS and LGE at 6SD were 0.732 vs 0.715 vs 0.74, 66.7% vs 59% vs 68.6, and 76.7% vs 80% vs 72.4%, respectively. See Table .22%], anIn this study,we demonstrated the following points: 1. HOCM patients with fQRS exhibited more extensive MF than those with normal QRS wave morphology; 2. Q-fQRS showed good correlation with the fibrotic state of the myocardium and was an independent predictor for MF in HOCM patients; and 3. compared with LGE at 6SD, Q-fQRS showed a similar sensitivity and specificity in identifying patients with severe MF and could be used as an effective and cost-efficient predictor to evaluate fibrotic burden.MF is one of the main pathological characteristics in HCM patients . MF is aTwelve-lead ECG is a simple and cost-efficient tool. Patients with HCM frequently exhibit a wide spectrum of ECG abnormalities, especially in HCM patients with LV outflow track obstruction . fQRS waHowever, fQRS is not limited to patients with cardiac diseases. fQRS is also present in almost 19.7% of subjects without a known cardiac disease and was not associated with increased mortality in these subjects. Although fQRS morphologies could be early markers of subclinical cardiac disease , it cannOne limitation of this study was that this was a retrospective study, however, we prospectively enrolled HOCM patients from 2015, and all patients were diagnosed and managed by protocol. Second,because the controls were coming from autopsies of 9 individuals who died from accidents, we had no access to their medical history. Third, sample size was small and restricted to HOCM, which needed to be validated in a larger HCM patient cohort. Fourth, our study limited to single samples of the septum obtained at surgical myectomy, so sampling in different regions might be essential to detect distribution of MF in HOCM patients. Fifth, the lack of long-term longitudinal follow up data prevented us from analyzing the prognostic effect in HOCM patients with high CVF and the influence of collagen accumulation during the development of HOCM.In conclusion, HOCM patients with the presence of fQRS showed greater histological MF. Q-fQRS was an independent predictor to detect MF and had a good diagnostic value of 66.7% sensitivity and 76.7% specificity to identify patients with higher fibrotic burden.