Rheumatoid arthritis (RA) patients have a 1.5- to twofold higher risk of developing heart failure (HF) and a twofold increased risk of HF-associated mortality compared to those without RA. HF is preceded subclinically by left ventricular (LV) remodeling in the general population. There is a relative absence of prospective studies following RA patients from pre-clinical to clinical HF as well as prospective studies of LV remodeling in RA without clinical HF. In our study, 158 RA patients without clinical HF were enrolled and underwent transthoracic echocardiography (TTE) at baseline and on follow-up between 4 and 6 years. Extensive characterization of RA disease activity and cardiovascular risk factors were performed. LV remodeling was prevalent at 40% at baseline and increased to 60% over time. Higher levels of interleukin-6 (IL 6) were associated with concentric LV remodeling on follow-up. The use of tocilizumab was also significantly associated with baseline LV remodeling . These findings suggest a role for IL-6 as a biomarker for LV remodeling in RA patients without clinical HF. Future research should focus on prospective follow-up of LV remodeling and the effects of IL-6 inhibition on LV remodeling in RA patients.The online version contains supplementary material available at 10.1186/s13075-023-03113-8. People with rheumatoid arthritis (RA) have a 1.5- to twofold higher risk of developing heart failure (HF) and a twofold increased risk of HF-associated mortality compared with people without RA. Emerging data suggest that the dominant clinical HF phenotype in RA appears to be HF with preserved ejection fraction (HFpEF) –5. Whilen = 158) was designed as a cross-sectional study in 2011 to identify myocardial phenotypes in RA patients without clinical cardiovascular disease (CVD). Patients were subsequently re-recruited for a follow-up visit 4–6 years later to investigate changes in LV structure and function over time; 60 participants completed the follow-up visit. Detailed inclusion/exclusion criteria have been published previously [The RHYTHM cohort . Baseline scans (n = 158) were re-read side by side with the follow-up scans (n = 60) by the same echocardiographer (KI) without blinding to time sequence.The protocol for transthoracic 2-dimensional (2D) echocardiography was detailed in prior manuscripts –12. Usin2.7 sex neutral; 50 g/m2.7 for men and 47 g/m2.7 for women) [2 for men and 24 mL/m2 for women), RWT (< 0.42) [Sex-neutral as well as sex-specific cut offs for LV structure derived from the general population were utilized: LVMI (51 g/mr women) , 16, ESV(< 0.42) –20, LVM (< 0.42) .2 for men and > 95 g/m2 for women, and the sex independent cut off is 51 g/ht2.7 and RWT > 0.42 [2or LVMI > 115 g/m2 and RWT > 0.42. Concentric remodeling (CRM) is defined as LVM < 95 g/m2 or LVMI < 115 g/m2 and RWT > 0.42. Eccentric hypertrophy (EH) is defined as LVM > 95 g/m2 or LVMI > 115 g/m2 and RWT < 0.42. However, because the RA patients in this study did not have clinical HF, we utilized LVMI > 90 percentile indexed to height2.7 with RWT > 0.42 to define LV remodeling categories. Categories were constructed without regard to sex, as 84% of our cohort was female and there were no statistical differences in LVMI ht2.7 in male vs female (p = 0.52) within our cohort. Thus, the following cut-offs were utilized to define remodeling states in this RA cohort: (1) normal geometry, LVMI < 90 percentile and RWT < 0.42 and (2) CRM, LVMI < 90 percentile and RWT > 0.42; (3) CH, LVMI > 90 percentile and RWT > 0.42; and (4) EH, LVMI > 90 percentile and RWT < 0.42.LV remodeling states are defined in the general population using standardized cut-off values of LVMI and RWT. General population cut-offs for elevated LVMI are > 115 g/mCardiac PET-CT scans were performed at baseline to measure myocardial 18F-fluorodeoxyglucose (FDG) uptake, rest and stress myocardial perfusion using 13N-ammonia, and coronary artery calcium (CAC). These methods have been described extensively in prior publications , 12.Phlebotomy was performed on the morning of each visit after an overnight fast. Details of laboratory measurements have been previously published . Cholestt-tests or the Wilcoxon-Mann–Whitney test/signed ranks. Categorical variables were compared using the chi-squared goodness of fit test, Fisher’s exact test, or McNemar’s test, as appropriate. Linear regression was used to model the associations of clinical and laboratory characteristics with the primary outcomes, CRM and RWT. Univariable and multivariable models were constructed to identify variables associated with these LV structural outcomes. Multivariable models were constructed by including any variable associated with the outcome (p < 0.25) in univariable models, and a p-value of < 0.05 was considered significant for final models. All multivariable models were examined for co-linearity, omitted variables, and outliers. All analyses were performed using Stata version 16 .Means and standard deviations (SDs) for normally distributed variables, and counts and percentages for categorical variables, were calculated. For continuous variables, differences were compared using Student’s n = 158) and the longitudinal subset (n = 60) at baseline were previously reported [Characteristics of the full cohort (reported  and are 2.7 (p < 0.01) sex neutral; 50 g/m2.7 for men (p < 0.01) and 47 g/m2.7 for women (p < 0.01)) [2 for men (p < 0.01), 61 mL/m2 for women (p < 0.01)); mean baseline ESVI of 17.7 + 5.06 (vs 31 mL/m2 for men (p < 0.01) and 24 mL/m2 for women (p < 0.01)), mean baseline RWT of 0.34 ± 0.09 (vs < 0.42 (p < 0.01)) [LV structural measures are summarized in Table < 0.01)) , 16; mea< 0.01)) .p < 0.01 and p < 0.05, respectively) while mean LVMI, EDVI and ESVI were not significantly different from baseline (p = 0.82).Mean baseline LVM indexed to EDV (LVM/EDV) of 1.33 ± 0.24 was above established cut-off values  . Fifty-eThe percentages of patients fulfilling LV remodeling criteria are shown in Table p = 0.053) but not with baseline CRM  and tocilizumab use  were associated with higher baseline RWT  (Supplementary Table p = 0.009)  . Similar analyses were performed for individual measures of wall thickness (RWT and LVM/EDV) Tables  and 3. IM Tables . In multThere were no significant associations  between measures of myocardial inflammation and perfusion vs baseline/follow-up LV structure, including CRM and RWT. Additionally, there were no significant associations  between BNP, troponin-I, and galectin-3 and baseline/follow-up LV structure, including CRM and RWT.LV structure is assessed by LVM and RWT on two or three-dimensional TTE. Several proxy measures for RWT exist, including LVM indexed to EDV dimensions. Generally, increased LVM and RWT indicate abnormal LV geometry.In this study, we confirmed that CRM, defined by increased RWT but normal LVM, is prevalent in RA patients without HF and, importantly, showed for the first time that the prevalence increases over time. Furthermore, our data suggest several inflammatory determinants of LV remodeling and its progression including higher IL-6 levels or use of an IL-6 inhibitor (tocilizumab), as well as demographic and CV determinants including age, BMI, and SBP.p < 0.05 for both), consistent with the overall increasing prevalence of CRM. Other individual LV structural parameters such as LVMI, EDVI, and ESVI did not change significantly on follow-up.In our prospective sub-cohort, CRM was the most prevalent form of remodeling at baseline (13%) and increased significantly to 31% on follow-up. RWT and LVM/EDV also both increased significantly over time  increase in IL-6 was associated with 2.5 times higher odds of CRM on follow-up. These findings are consistent with the hypothesis that higher levels of IL-6 induce adverse LV structure/geometry, likely mediated by activation of pro-fibrotic and myocyte hypertrophy pathways –27. Tocin = 3) and on follow-up (n = 6), meaningful statistical differences in IL-6 levels could not be inferred. However, IL-6 levels were consistently higher in those on tocilizumab vs those not on tocilizumab (results not shown), which may reflect an accumulation of free/unmetabolized IL-6 in circulation resulting from uptake of IL-6 receptors after tocilizumab treatment.In as far as the association between tocilizumab and IL-6 levels are concerned, given the small numbers of patients on tocilizumab at baseline , we were still able to detect significant changes in key parameters of LV structure.In conclusion, LV remodeling is prevalent in RA patients without clinical HF and increases to 60% over time. Adverse LV structure/remodeling at baseline and follow-up are associated with higher IL-6 levels and use of tocilizumab. These findings suggest that inflammatory cytokines such as IL-6 could serve as biomarkers for LV remodeling in RA patients and possibly future development of HF. Investigating whether LV remodeling leads to clinical HF in RA patients and whether LV remodeling is reversible or attenuated by IL-6 inhibition (tocilizumab) remain key future research objectives, ultimately to reduce the twofold higher HF mortality rate associated with RA vs non-RA .Additional file 1: Table S1. Follow-up CRM *excluded to those who did not have CRM at baseline*.Table S2. Baseline LVM/EDV.Table S3. Annualized Rate of Change in LVM/EDV. Table S4. Baseline 3D LVMI ht2.7 > 90%. Table S5. Annualized Rate of Change in LVMI2.7


Late gadolinium enhancement (LGE) detected by cardiac MRI (CMR) has low correlation with low voltage zones (LVZs) detected by electroanatomical mapping (EAM). We aim to study correlation of myocardial strain by CMR- Feature Tracking (FT) alongside LGE with LVZs detected by EAM.Nineteen consecutive CMRs of patients with EAM were analyzed offline by CMR-FT. Peak value of circumferential strain (CS), longitudinal strain (LS), and LGE was measured in each segment of the left ventricle (17-segment model). The percentage of myocardial segments with CS and LS > −17% was determined. Percentage area of LGE-scar was calculated. Global and segment–wise bipolar and unipolar voltage was collected. Percentage area of bipolar LVZ (<1.5 mV) and unipolar LVZ (<8.3 mV) was calculated.r = +0.5, p = 0.03) and combined percentage CS+LS abnormality with percentage unipolar LVZ . Per-unit increase in CS increased the percentage area of unipolar LVZ by 2.09 (p = 0.07) and per-unit increase in LS increased the percentage area of unipolar LVZ by 2.49 (p = 0.06). The concordance rates between CS and LS to localize segments with bipolar/unipolar LVZ were 79% and 95% compared to 63% with LGE.Mean age was 62±11 years. Mean LVEF was 37±13%. Mean global CS was −11.8±5%. Mean global LS was −11.2±4%. LGE-scar was noted in 74% of the patients. Mean percentage area of LGE-scar was 5%. There was significant correlation between percentage abnormality detected by LS with percentage bipolar LVZ (Myocardial strain detected by CMR-FT has a better correlation with electrical low voltage zones than the conventional LGE.The online version contains supplementary material available at 10.1007/s10840-023-01553-5. Cardiac magnetic resonance (CMR) imaging is one of the most important diagnostic tools for characterization of myocardial diseases . Late gaNovel CMR parameters such as T1 mapping have recently been shown to be better predictors of the intramural concealed fibrosis seen in NICM . MyocardOur study population consisted of consecutive patients with NICM enrolled prospectively for CMR studies presenting to the Canberra Heart Rhythm Centre, in the period between November 2019 and November 2021. The patients underwent invasive electrophysiological studies with voltage mapping and radiofrequency ablation when deemed necessary. The diagnosis of NICM was made with corroborative evidence of LV dysfunction (LV ejection fraction <50%), in the absence of significant coronary artery disease (>50% stenosis as assessed by coronary angiography). The following categories of NICM were excluded: congenital heart diseases; hypertrophic cardiomyopathy; arrhythmogenic right ventricular cardiomyopathy (ARVC); and LV noncompaction. In addition, pacing-dependent patients, persistent/long standing atrial fibrillation patients were excluded for the study. The study was conducted as per the ethical guidelines of the Declaration of Helsinki and was approved by the Human Research and Ethics Committee of The Canberra Hospitals (2019/ETH13256).CMR was performed on a 1.5 T scanner  with a cardiac phased-array receiver surface coil and electrocardiogram (ECG) gating. For the assessment of LV functions, cine imaging was performed by using a steady-state free precession (SSFP) sequence in the vertical long axis, horizontal long axis and short axis. In patients with devices, Turbo Spin echo for cine imaging was used when significant susceptibility artifact was present on SSFP imaging. Patients with significant artifacts due to devices were excluded from the study. Pacing-dependent patients were excluded from the study. In patients with cardiac resynchronization devices, biventricular pacing was on. Standard parameters were repetition time/echo time 3.6/1.8 ms; sense factor 2, flip angle — 60°; section thickness — 8 mm; field of view — 300 mm. For scar assessment, LGE images covering the entire LV were acquired approximately 15 min after an intravenous injection of 0.2 mmol/kg gadobenate dimeglumine contrast agent. The LGE-images were acquired using a magnitude inversion-recovery (IR) or phase sensitive inversion recovery (PSIR) gradient–recalled echo sequence with 8.0 mm slice thickness. A wideband LGE sequence was used to minimize artifacts from the battery pack in subjects with device implants.www.medviso.com/segment). The base and the apex of the LV were defined from the short-axis slices. The endocardial and epicardial borders were traced manually in the short axis, apical 3-chamber long-axis, apical 2-chamber long-axis and apical 4-chamber long-axis images in end-diastole and end-systole. Adequate precaution was exercised to avoid blood pool contamination and to exclude the papillary muscles. CMR studies with poor image quality or missing slices were excluded from the analysis. Segmentation of the LV into the standard 17-segments was carried out by the software  Global circumferential and longitudinal strain has moderate correlation with percentage area of bipolar and unipolar LVZs; [2] Percentage segmental abnormality detected with combined circumferential and longitudinal strain has good correlation with percentage area of unipolar LVZs; [3] Localization of abnormalities with CMR-FT strain resulted in better concordance rates of 89% with a composite of circumferential and longitudinal strain compared to only 63% with LGE, for detection of bipolar or unipolar LVZs.The distribution of fibrosis in NICM is complex. A histological validation of fibrosis patterns in NICM showed patchy and/or diffuse distribution . The intThe architecture of the LV myocardium is such that the subendocardial and epicardial fibers are longitudinally oriented and the midmyocardial fibers are circumferentially oriented. Considering the more common mid-wall patchy distribution of scar in NICM, circumferential strain is likely to pick up these abnormalities . LongituThe highlight of our study is the higher concordance rate of myocardial strain compared to LGE to detect electrical abnormalities. In patients with right ventricle cardiomyopathies, the correlation between LGE and EAM-LVZs was only 48%. In the same study, 91% of patients with percentage area of EAM-LVZ <20% had no LGE, and endomyocardial biopsy was considered a better tool to correlate with EAM-LVZs . In a stMyocardial strain analysis can be performed by speckle-tracking echocardiography (STE) as well. In a recent study, endocardial longitudinal strain by STE correlated strongly with percentage bipolar low voltage zone and mid-myocardial longitudinal strain correlated strongly with percentage unipolar low voltage zone. In the same study, the concordance rate for regional abnormalities of strain with the LVZs was 75% . As myocAlternative CMR diagnostic tools, such as T1 mapping and ECV estimation, are being explored to see whether they better correlate with electrical abnormalities in NICM. In a study on 36 patients with dilated cardiomyopathy, native T1 mapping values and ECV estimation had strong correlation with the collagen fraction noted in the biopsy and was better than LGE in detection of diffuse microscopic fibrosis . In anotIn a large cohort of patients with NICM, the presence of LGE and epicardial or transmural distribution of LGE were significant predictors of ventricular arrhythmic events across different strata of LVEF . Though The results of the study should be interpreted in the context of the relatively small sample size of the study and small number of events over follow-up. The cut-off of −17% applied for segmental strain abnormalities was the same as for global strain values, however this needs large scale validation. CMR analysis might not be accurate in patients with bundle branch blocks (5 patients) and high PVC burden (4 patients), though this number was small in this study. This study did not test strain measurements by tissue tagging methods, such as Fast-SENC strain. CMR-FT, despite its distinct advantages, is subject to through-plane motion artefacts. This study did not test other CMR measures like T1 mapping values, assessment of ECV and perfusion scores. Further studies are needed to determine whether these investigations can complement LGE in the risk stratification for sudden cardiac death. Since the introduction of 8.3 mV as the cut-off for defining unipolar low voltage zones, a lot of studies have retained this value. We have also used the same cut-off for defining the unipolar low voltage zones. However, these cut-off values are likely to change, while using high-density mapping with multi-electrode catheters.Our study concludes that abnormal myocardial strain detected by CMR-FT method is more closely related to electrical abnormalities, than the conventional LGE detected by CMR. Localization of low voltage zones with CMR-strain has better concordance than LGE. Thus, CMR-strain can inform the operator about specific regions of substrate abnormalities during a VT ablation procedure, especially in the absence of LGE scar. Our study emphasizes the need to look beyond LGE detected by CMR with novel parameters such as CMR-strain while correlating with the LV electrical abnormalities.In patients with nonischemic cardiomyopathy, late gadolinium enhancement detected by CMR, while having important prognostic implications, has a poor concordance rate with electrical abnormalities detected by electro-anatomical mapping studies. Alternate measures like T1 mapping values, extracellular volume estimation and myocardial strain are being evaluated to better correlate with low voltage regions of the left ventricle.Myocardial strain picked up by CMR-feature tracking has good correlation with unipolar low voltage zones. The strain parameters can also be used to detect the segmental abnormalities with concordance rates better than late gadolinium enhancement. This is important for the operator to understand the underlying abnormalities while attempting ablation of the substrate.Supplementary file 1Supplemental Table S1: Segmental values of measured parameters from cardiac MRI and Electroanatomical mapping, Supplementary Table S2: Bivariate correlation between the measured parameters


The aim of the present review is to highlight the strengths and limitations of echocardiographic parameters and scores employed to predict favorable outcome in complex congenital heart diseases (CHDs) with borderline right ventricle (RV), with a focus on pulmonary atresia with intact ventricular septum and critical pulmonary stenosis (PAIVS/CPS). A systematic search in the National Library of Medicine using Medical Subject Headings and free-text terms including echocardiography, CHD, and scores, was performed. The search was refined by adding keywords “PAIVS/CPS”, Ebstein’s anomaly, and unbalanced atrioventricular septal defect with left dominance. A total of 22 studies were selected for final analysis; 12 of them were focused on parameters to predict biventricular repair (BVR)/pulmonary blood flow augmentation in PAIVS/CPS. All of these studies presented numerical (the limited sample size) and methodological limitations . There was heterogeneity in the echocardiographic parameters employed and cut-off values proposed, with difficultly in establishing which one should be recommended. Easy scores such as TV/MV  and RV/LV (right/left ventricle) ratios were proven to have a good prognostic accuracy; however, the data were very limited (only two studies with <40 subjects). In larger studies, RV end-diastolic area and a higher degree of tricuspid regurgitation were also proven as accurate predictors of successful BVR. These measures, however, may be either operator and/or load/pressure dependent. TV Z-scores have been proposed by several authors, but old and heterogenous nomograms sources have been employed, thus producing discordant results. In summary, we provide a review of the currently available echocardiographic parameters for risk prediction in CHDs with a diminutive RV that may serve as a guide for use in clinical practice. Borderline right ventricle (RV) encompasses a wide spectrum of complex congenital heart diseases (CHDs) with neonatal presentation including pulmonary atresia with intact ventricular septum (IVS), critical pulmonary stenosis (CPS), ,11,12,13In June 2022, we performed a systematic search in the National Library of Medicine for Medical Subject Headings and free-text terms including “echocardiography,” “congenital heart disease”, and “scores”. The search was refined by adding keywords for “pulmonary atresia intact ventricular septum” and “critical pulmonary stenosis,” “ Ebtsein’s anomaly”, and “uAVSD with left dominance”. The titles and abstracts of articles identified were evaluated and excluded if:  the repoFrom 48 studies initially selected, 22 original studies ,23,25,26Echocardiographic parameters able to determine favorable immediate ,3,4,6,10Inclusion criteria were different in most studies, including only those children undergoing percutaneous balloon pulmonary valvuloplasty as an initial procedure ,6,8,9,10Endpoints were also different between studies, comprising of the need for PDA stenting or BTT ,4,6,8 reExclusion criteria were often poorly defined, and when they were specified ,12,13,14Tricuspid valve Z-scorep = 0.071).Many authors used TV Z-scores as an indicator for the need of PDA stenting or BTT ,4,6, re-TV/MV annular ratioThe use of the TV/MV annular ratio may overcome the issues related to the use of different Z-scores. The TV/MV annular ratio is an easy and very reproducible measurement, independent of external formulas, that has been employed by several authors ,4,5,13 . SimilarTricuspid regurgitationThe degree of tricuspid regurgitation (TR) is an important indicator for successful BVR ,2. MaskaEvaluation of RV size is difficult at echocardiography and may be even more difficult in hypoplastic, hypertrophied bipartite RV, such as those in neonates with PAIVS.RV diametersp = 0.027) [An easy way to measure RV dimensions is to calculate the lateral diameter and base–apex length in the four-chamber view . The RV/Right ventricle end-diastolic (RVED) area2/m2 for BVR [2 for ductal dependency after PBPV [2/m2 had a sensitivity of 93% and a specificity of 80% in predicting BVR. Petit and colleagues [n = 17) compared with those who underwent biventricular repair (n = 82) . The RVED area had an odds ratio of 0.81 per 0.1 cm2 increase  for the prediction of BVR, however, cut-off values were not proposed (2). Lastly, Giordano et al. indicated a value for the RVED area of 1.35 cm2 as a risk factor for duct-dependent pulmonary circulation after PBPV in PAIV [Another technique to measure RV size by echocardiography is to trace the end-diastolic area in the four-chamber view. However, the tracing of endocardial borders may be quite difficult in very hypertrophied, trabeculated RV such as those of neonates with PAIVS/CPS . RV area for BVR  to 1.35 Composite scores and other indices2, right atrial (RA) area > 2.45 cm2, % of PFO right-to-left shunt > 69.5%, moderate/severe TR, RV systolic pressure > 42.5 mmHg, tricuspid E/E′ ratio > 6), each of them assigning one point if reaching the cut-off value. A score ≥ 4 had a 100% sensitivity and 86% specificity in predicting the need for PDA stenting/shunt in 55 neonates with PA-IVS/CPS  nor the Celermajer’s index (p = 0.958) was significantly related to death. Instead, univariate analysis revealed that fetal distress (p = 0.002), prematurity (p = 0.036), low birth weight (p = 0.003), diameter of the ASD (p = 0.002), and pulmonary stenosis/atresia (p = 0.001) were related to mortality. On multivariate analysis, however, only fetal distress (p = 0.004) and pulmonary atresia/stenosis (p < 0.001) remained significant determinants of outcome [In 2013, Yu et al.  reviewed outcome . Both st outcome ,21 suffe outcome ,21. Furtn = 9) or isolated TV dysplasia (n = 3), six underwent a BVR and three survived [p < 0.001), and the presence of pericardial effusion (p = 0.04) [In a retrospective surgical series from 2016  on 12 nesurvived . A TR flsurvived . A study = 0.04) .Unbalanced atrioventricular septal defect (UAVSD) with left dominance is usually defined when the atrioventricular valve index (AVVI)  is >0.6 ,24,25,262) or AVVI  and apex-forming ventricles [2) and near apex-forming ventricles, single ventricle palliation and ventricular recruitment with subsequent staged biventricular conversion was advised, whereas univentricular palliation was advised only in UAVSD with severe ventricular hypoplasia  [Later, Nathan et al.  reviewedntricles . In contrriding) .Although echocardiography is often the primary and sometimes only imaging modality for pre-surgical/interventional diagnosis in complex neonatal CHDs characterized by borderline RV, the echocardiographic indicators available for risk prediction in this cardiac lesion remain limited.All the literature data reviewed herein showed significant methodological limitations, including a single-center design ,21,25,26A series of echocardiographic parameters have been proposed for BVR risk assessment in patients suffering from PAIVS/CPS ,11,12,13The use of composite scores with multiple markers, as recently proposed, seems to be a reasonable approach for future studies . There ip = 0.002). Typically, echocardiography tends to overestimate the severity of Ebstein’s anomaly, although underestimations can rarely occur [In summary, there is a shortage of echocardiographic studies clarifying prognostic indicators in other forms of borderline RV including Ebstein’s anomaly  ,19,20,21ly occur .The available literature describing UAVSD is extremely limited ,26, sincOur review summarizes the strengths and limitations of the current echocardiographic indices to predict successful BVR and the need for reintervention/pulmonary blood flow stabilization in complex neonatal CHD with borderline RV, with a specific focus on PAIVS and CPS. Examining the echocardiographic evaluation of disease severity is crucial for complex CHD’s encountered in daily practice and should serve as a guide for further research that would appear to be necessary based on the observations from this review.


Biological valve failure (BVF) is an inevitable condition that compromises the durability of biological heart valves (BHVs). It stems from various causes, including rejection, thrombosis, and endocarditis, leading to a critical state of valve dysfunction. Echocardiography, cardiac computed tomography, cardiac magnetic resonance, and nuclear imaging play pivotal roles in the diagnostic multimodality workup of BVF. By providing a comprehensive overview of the pathophysiology of BVF and the diagnostic approaches in different clinical scenarios, this review aims to aid clinicians in their decision-making process. The significance of early detection and appropriate management of BVF cannot be overstated, as these directly impact patients’ prognosis and their overall quality of life. Ensuring timely intervention and tailored treatments will not only improve outcomes but also alleviate the burden of this condition on patients’ life. By prioritizing comprehensive assessments and adopting the latest advancements in diagnostic technology, medical professionals can significantly enhance their ability to manage BVF effectively. In the last 20 years, the use of mechanical heart valves (MHVs) has declined progressively in favor of the use of biological heart valve (BHV) implantations, which have seen an 80% increase . The excThe most commonly implanted BHVs are xenografts made of bovine or porcine pericardia and porcine aortic valves pretreated with chemical agents  that reduce the immunogenicity of the BHV. Another nonmechanical alternative to BHV is represented by transcatheter heart valves (THVs), which were introduced in 2002. THVs consist of metal stent valves made of cobalt or nitinol with bovine or porcine pericardial leaflets inside . Both suA dysfunctional bioprosthetic valve (BV) is a condition in which the normal function of a BV is altered for structural and nonstructural reasons. Nonstructural BVDs include all conditions that do not implicate a morphological alteration of the components of the valve: prosthesis–patient mismatch, paravalvular regurgitation (with preserved integrity of the BV apparatus), inappropriate positioning of the valve, embolization, or dislocation. Structural BVD is instead determined by pathological changes of the BV: leaflets’ wear and tear, disruption, flail, fibrosis and calcification, strut or stent fracture, or deformation. Structural BVD can also be determined by valve thrombosis or endocarditis. Once structural or nonstructural valve dysfunction occurs, signifying BVD, the process can progress to BVF, a condition characterized by new symptoms’ onset, worsening of the left ventricular function/dimension, or pulmonary hypertension. Finally, BVF can lead to valve reintervention or death.In the following paragraphs, we focus on organic causes of BVF: SVD, thrombosis, and endocarditis.2+) into the prosthetic leaflets mediated by chemical pretreatment and precipitation of calcium phosphates (CaPs) into the cells, the collagen, and the elastin fibers. Recipient-related factors  can accelerate calcium deposition together with a cellular-recipient-mediated response through macrophages and red blood cells (RBCs). Macrophages infiltrate the BHV leaflets, leading to apoptosis and CaPs’ deposition, while internalized RBCs cause intra-valvular iron deposition and mineralization. In addition, BHVs are not able to produce an extracellular matrix (ECM) and perform self-repair in response to mechanical stress [Native heart valves are a complex multicellular system that is able to self-repair in response to mechanical, hemodynamic, and chemical stressors that occur at every cardiac cycle . On the l stress . Togethel stress . This rel stress ; the staA meta-analysis published in 2001 that included 5837 patients showed an annual rate of valve thrombosis of about 0.03% 0.3% at 10 years) ; however years ; Valvular thrombosis can be classified into two categories: subclinical thrombosis and clinically significant thrombosis ,12. If tThe risk of infective endocarditis (IE) is ten times higher in prosthetic heart valves (PVs) than in native heart valves (NVs). Between 10 and 30% of all endocarditis affect PV, with the same incidence among mechanical and biological PV. While staphylococci endocarditis is more frequent during the first year after surgery, other microorganisms seem to cause late-onset endocarditis (mainly streptococci and enterococci) . Early eTTE is the first-line diagnostic tool for detection of BVD . The curIn recent studies ,31, a prA poor acoustic window and contraindication to TEE can limit the echocardiographic evaluation in the case of BVD. Cardiac CT (CCT) overcomes these limitations thanks to its higher spatial resolution and its noninvasive nature . CCT emeCardiac magnetic resonance imaging (CMR) plays a relatively limited role in the evaluation of BVD . CMR has18F-fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) and white-blood-cell single-photon emission CT/CT (WBC SPECT/CT) can integrate the initial evaluation of BV diseases  [A suggested algorithm for the management of bioprosthetic valve dysfunction is provided in 2) , short B2) , acute m2) .Endocarditis, degeneration, and thrombosis can impact the lifespan of BV and often manifest with similar clinical presentations. The integration of all imaging modalities is crucial for achieving an accurate diagnosis and guiding subsequent patient management. Understanding the strengths and limitations of each modality is essential in identifying the trajectory toward biological valve failure and guiding appropriate therapy and reintervention.


We evaluated the effects of varying blood flow rate during peripheral veno-arterial extracorporeal membrane oxygen (V-A ECMO) on left ventricular function measured by two-dimensional strain.Adult patients who were supported by peripheral V-A ECMO were recruited. Serial hemodynamic and cardiac performance parameters were measured by transthoracic echocardiogram within the first 48 h after implementation of V-A ECMO. Measurements at 100%, 120%, and 50% of target blood flow (TBF) were compared.p < 0.001], stroke volume was greater , and cardiac index was higher . Left ventricular contractile function measured by global longitudinal strain improved at 50% compared with 100% TBF . Similarly, left ventricular ejection fraction increased  and left ventricular outflow tract velocity time integral increased . Adding echocardiographic parameters of left ventricular systolic function to the Survival After Veno-arterial ECMO (SAVE) score had better discriminatory value in predicting eventual hospital mortality  and successful weaning from V-A ECMO .A total of 54 patients were included and the main indications for V-A ECMO were myocardial infarction [32 (59.3%)] and myocarditis [6 (11.1%)]. With extracorporeal blood flow at 50% compared with 100% TBF, the mean arterial pressure was lower [66 ± 19 vs. 75 ± 18 mmHg, In the initial period of V-A ECMO support, measures of left ventricular function including left ventricular ejection fraction and global longitudinal strain were inversely related to ECMO blood flow rate. Understanding the heart-ECMO interaction is vital to interpretation of echocardiographic measures of the left ventricle while on ECMO. Due to In the peripheral configuration of V-A ECMO, oxygenated blood from the ECMO circuit returns to the arterial system in a “retrograde” manner from cannulas sited in peripheral vasculature, most commonly the femoral artery. This returning blood flow may increase the left ventricular (LV) afterload, leading to increase in LV wall stress and myocardial oxygen demand, a condition that may be deleterious to the recovery of an acutely-injured heart , 4. AlthIn this prospective observational study, we utilized detailed echocardiography and strain analyses to examine LV function in response to different levels of ECMO blood flow during acute cardiogenic shock. We hypothesized that the association between LV systolic function and ECMO blood flow rate during the initial period of peripheral V-A ECMO support can be measured by two-dimensional strain.2.2.1.This was a single-center prospective observational study including all adult patients (≥18 years old) with acute cardiogenic shock who were admitted between April 2019 and December 2021, and were treated with peripheral V-A ECMO in a tertiary referral center in Hong Kong.Patients were excluded if they met one of the following criteria: (1) clinically unstable hemodynamics including unstable or poor ECMO blood flow which precludes ECMO flow adjustment; (2) presence of pathological intracardiac shunt, for example, ventricular septal defect; (3) presence of iatrogenic shunt, for example, left ventricular vent; (4) echocardiographic image quality unsatisfactory for data processing; or (5) absence of patient or surrogate consent. Patients who had concurrent use of intra-aortic balloon pump (IABP) were not excluded. This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (HKU/HA HKW IRB) (IRB Reference Number: UW 17–449). Informed consent was obtained from all participants or their surrogates if the fitness to consent was impaired.2.2.Transthoracic echocardiogram (TTE) examinations were performed as soon as practicable within the first 48 h after initiation of V-A ECMO support by one of the 3 physicians trained in detailed cardiac echocardiography, using a commercially available system . Two-dimensional sequences with three beats were obtained using a 3.5 MHz ultrasound transducer probe at a frame rate of 50 frames/s and stored digitally in Digital Imaging and Communications in Medicine (DICOM) format. Standard echocardiographic measurements were obtained according to current recommendations , and repLV systolic function assessment included traditional parameters of left ventricular ejection fraction (LVEF), fractional shortening (FS), left ventricular outflow tract (LVOT) velocity-time integral (VTI), left ventricular index of myocardial performance (LIMP), and peak systolic tissue velocity (s') at the mitral annulus measured by pulsed-wave Doppler. LVEF was measured using both the linear (Teichholz formula) and biplane Simpson methods. Two-dimensional strain for each of the LV segments were measured by speckle tracking echocardiography in longitudinal 3-chamber, 4-chamber and 2-chamber planes. The LV global longitudinal strain (GLS) was obtained by averaging segmental strain values. All echocardiographic measurements were analyzed offline by a single investigator blinded to clinical data and subsequent analyses. Detailed definitions of these measurements are shown in Hemodynamic data were measured by continuous invasive measurement of arterial pressure and by parameters obtained during transthoracic echocardiography according to current recommendations . Patient2.3.The primary outcome was the LV systolic function measured by two-dimensional GLS. Secondary outcomes were other measures of LV systolic function, including LVEF using modified Simpson's rule, LVOT VTI, LIMP, and s' at the lateral and septal mitral annular level.2.4.2.4.1.Data were expressed either as mean ± standard deviation or median with interquartile ranges for continuous variables, and frequencies with percentages for categorical variables. Comparisons between LV parameters at different ECMO flow rates were made using paired t-tests or Wilcoxon signed-rank tests.2.4.2.We examined whether data gathered early after ECMO implantation is useful to predict eventual clinical outcomes. The performance of 2 different models were assessed—Model 1 was the Survival After Veno-arterial ECMO (SAVE) score ; Model 22.4.3.It is possible that the concurrent use of IABP affects echocardiographic parameters of LV function, therefore, a subgroup analysis excluding patients on IABP during ECMO was performed.P value of less than 0.025 was considered statistically significant.Data management and statistical analyses were performed in Stata, version 13 (StataCorp LP). Bonferroni correction was used to adjust for multiple comparisons, and a two-tailed 3.3.1.From 1st April 2019 to 31st December 2021, 90 adult patients who were admitted to the intensive care unit (ICU) with a diagnosis of cardiogenic shock requiring V-A ECMO support were identified . After eThe median age of the study population was 59 (50–65) years and there were 40 (74.1%) males. The most common indications of V-A ECMO were acute coronary syndrome  and myocarditis . Baseline characteristics are summarized in On day 1 of ECMO support, the median of the lowest mean arterial pressure (MAP) was 55 (45–76) mmHg and the highest heart rate were 115 (101–126) bpm. The vasoactive inotropic score was 24.8 (6.6–48.7), and the mean of the highest lactate level was 11.6 ± 5.9 mmol/L. The mean APACHE IV score was 122.4 ± 28.5. Detailed clinical parameters are summarized in 3.2.The median duration on V-A ECMO was 120.3 (70.3–188.0) hours. There were 25 (46.3%) patients who were able to be weaned off ECMO. A total of 25 (46.3%) patients survived the ICU stay and 23 (42.6%) patients survived the hospital stay. There were 2 (3.7%) patients who had IABP inserted prior to V-A ECMO, and 5 (9.3%) patients required IABP insertion after ECMO was initiated. The clinical outcomes stratified by SAVE score are shown in 3.3.p < 0.001; 66 ± 19 vs. 77 ± 17 mmHg, p < 0.001; respectively). Having ECMO blood flow at 50% TBF when compared with 100% TBF and 120% TBF was associated with higher stroke volume (SV) , and higher cardiac index (CI) , respectively.There were significant differences in hemodynamic parameters with ECMO blood flows at 50% compared with 100% and 120% TBF. The MAP was significantly lower at 50% compared with 100% TBF, and at 50% compared with 120% TBF  vs. 0 (−3.8–0) %, p < 0.001], respectively. Similarly, there were significant differences in segmental strain values obtained at the LV longitudinal 3-chamber, 2-chamber, and 4-chamber views when ECMO blood flow was titrated.TTE were performed on a mean 1.0 ± 0.7 days after initiation of ECMO. The myocardial systolic function measured by LV GLS was significantly better at 50% TBF compared with 100% TBF and 120% TBF , FS , LIMP , LVOT VTI , and s' measured at the medial  and lateral mitral annulus . Detailed echocardiographic data at different levels of ECMO blood flows are shown in The LV systolic function was significantly better across all echocardiographic measurements at 50% TBF compared with 100% TBF, and at 50% TBF compared with 120% TBF. These included the LVEF measured by the biplane method [24.4 (15.8–35.5) vs. 16.7 (10.0–28.5)%, 3.6.p = 0.008 vs. 0.62, 95% CI 0.46–0.78, p = 0.15; respectively) and successful weaning from V-A ECMO  .The performance of 2 clinical models including data gathered early after ECMO implantation to predict eventual hospital mortality and successful weaning from V-A ECMO were examined. The addition of echocardiographic parameters of LV systolic function obtained at 100% TBF (Model 2) resulted in better discriminatory value compared with SAVE score only in predicting the hospital mortality  . Hosmer-3.7.7 (13.0%) patients who had IABP during ECMO were excluded from the subgroup analysis. All indices of LV systolic function including strain measurements were significantly better at 50% TBF were compared with 100% and 120% TBF, respectively .4.In a prospective cohort of patients on V-A ECMO, the use of two-dimensional strain provided robust echocardiographic evidence of the afterload effect of peripheral V-A ECMO support during the acute phase of myocardial injury. Across different echocardiographic parameters, decreasing ECMO blood flow was associated with significantly measures increased LV systolic function. These physiological data are fundamental to understanding the heart-ECMO interaction, interpreting echocardiographic measures of LV function, guiding titration of ECMO blood flow, and optimizing cardiac recovery.The prevalent beliefs about hemodynamics during peripheral V-A ECMO include a decrease in the SV and cardiac output due to reduction in native cardiopulmonary circulation and an increase in the LV afterload , 11. DepThe optimization of ECMO blood flow for the heterogeneous conditions necessitating V-A ECMO is a complex issue, with sparse evidence for specific targets in published literature. Considering that initial ECMO set up is largely titrated to a target flow, this “ECMO dose” should be better delineated. While a general target ECMO flow of 50–80 ml/kg/min have been proposed , 8, otheWe highlighted that quantitative echocardiography in the management of patients requiring V-A ECMO extends beyond assessment of myocardial function at stably maintained ECMO flows . Recent The SAVE score is one of the most widely accepted risk prediction models to estimate hospital survival for patients on V-A ECMO . HoweverOne of the limitations of this study is its single-centered design, with possible systemic biases in patient selection and management. However, the inclusion criteria were not restrictive, and this is one of the larger V-A ECMO cohorts with detailed echocardiographic documentation of the heart-ECMO interaction at various flow rates. Second, patients who were hemodynamically unstable during the first 48 h and patients who had LV venting had to be excluded by nature of the study design, potentially limiting the application of the study findings to these patients. Third, other aspects of patient management, including the use of inotropes and titration of positive end-expiratory pressure were not protocolized, possibly introducing variable effects on preload and afterload.5.We provided echocardiographic data to demonstrate the inverse effects of ECMO blood flow on LV systolic function in a dose-dependent manner. These physiological data highlight the significance of determining goals of ECMO flow after initiation. Two-dimensional strain should be considered a promising tool for repeatable assessment of LV function for patients on V-A ECMO.


P < 0.05). The independent predictors of obstructive CAD were age , left ventricular ejection fraction , and GLS . CT-derived GLS of the left ventricle is correlated with CAD-RADS levels and CACs. It may be a better indicator than CACs to reflect the severity of CAD.To evaluate myocardial strain in patients with different coronary artery disease-reporting and data system (CAD-RADS) levels using the computed tomography (CT) feature tracking technology and to investigate the relationship of myocardial strain with coronary artery calcium scores (CACs) and the degree of coronary artery stenosis. We prospectively enrolled 237 consecutive patients to undergo coronary CT angiography. The participants were divided into the following groups: control (n = 87), CAD-RADS 1 (n = 43), CAD-RADS 2 (n = 43), CAD-RADS 3 (n = 38), and CAD-RADS 4 and above (n = 26). Myocardial strains were analyzed by commercial software, and CACs and coronary stenosis were assessed on post-processing stations. Differences between multiple groups were analyzed using one-way analysis of variance or the Kruskal–Wallis test. Logistic regression were used to analyze the effects of dichotomous variables. As the CAD-RADS level increased, the global circumferential strain (GCS), global longitudinal strain (GLS) and global radial strain (GRS) of the left ventricle based on CT gradually decreased. A significant correlation was observed between global myocardial strain and CACs (GRS: r =  − 0.219, GCS: r = 0.189, GLS: r = 0.491;  Coronary artery calcium score (CACs) is well known as an independent predictor of future coronary events. Quantifying CACs can aid in the prediction of future cardiovascular disease, and an increased CACs is directly related to increased disease risk2. The value of myocardial strain for diagnosis and risk stratification has been demonstrated in various cardiovascular diseases, such as severe aortic stenosis3, aortic valve replacement5, adult congenital heart disease6, isolated left anterior descending coronary stenosis7, and myocardial infarction8.Coronary artery disease (CAD) is a major cardiovascular disease in many countries worldwide. In 2016, the American Heart Association published an updated heart disease and stroke statistics report, which stated that 15.5 million people over the age of 20 in the United States have CAD9. Echocardiography and cardiac magnetic resonance (CMR) are currently used to quantify local systolic cardiac function11. Due to the angle dependence, sound window limitation, and manipulator dependence of echocardiography and the long acquisition time of CMR, cardiac computerized tomography (CT) has become a rapid, valuable method for assessing myocardial strain and is in good agreement with echocardiography and CMR13.Myocardial feature tracking is a highly reproducible method for measuring myocardial strainTherefore, this study aimed to evaluate the differences in CT-derived myocardial strain in patients with different CAD-reporting and data system (CAD-RADS) levels and investigate the relationship of cardiac CT-based myocardial strain with coronary artery calcium scores (CACs) and the degree of coronary stenosis.14; based on the CAD-RADS level, the patients were divided into groups I (CAD-RADS 1), II (CAD-RADS 2), III (CAD-RADS 3), and IV (CAD-RADS 4 and 5). Patients with evidence of arrhythmia, valvular heart disease, cardiomyopathy, congenital heart disease, or poor image quality or those with a history of coronary reconstruction were excluded. The inclusion criteria for the control group were as follows: (1) no history of CAD (≥ 1% diameter stenosis assessed via CTA), cardiomyopathy, valvular heart disease, or other cardiovascular diseases, (2) no hypertension, diabetes, or dyslipidemia, and (3) normal electrocardiograph (ECG) findings obtained 2 weeks before CTA. All subjects with renal dysfunction (glomerular filtration rate < 30 mL/min/1.73 m2), pregnant women, and children were excluded.The study was approved by the ethics committee. Patients with suspected CAD  were prospectively enrolled to undergo coronary CT angiography (CTA) to rule out CAD in the Union Hospital in Wuhan from August to November 2020. The CAD-RADS classification was implemented as described in the Cardiology of the American Expert Consensus document7. Family history of CAD was defined as a confirmed diagnosis of CAD in an immediate family member. Patients with incomplete clinical information were excluded from the analysis.Data on medical comorbidities were obtained from patients through questionnaires. Hypertension was defined as systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg, or use of antihypertensive medication. Diabetes was defined as the 2-h plasma glucose > 200 mg/dL during an oral glucose tolerance test (OGTT), or use of glucose-lowering medication. Dyslipidaemia was defined as total cholesterol > 5.7 mmol/L, low-density lipoprotein cholesterol > 4.1 mmol/L, triglyceride > 1.7 mmol/L, or use of cholesterol-lowering drugs. Non-smokers were defined as having less than 100 lifetime cigarettes, and the rest of the patients were categorized as regular smokers. Patients who drank alcohol were defined as having a positive history of alcohol consumptionCardiac CT was performed using the Siemens third-generation dual-source CT scanner . Patients with heart rates above 90 bpm received 25–50 mg metoprolol  to control heart rate and then, took nitroglycerin  orally to dilate coronary arteries 3–5 min before examination. Participants were trained to inhale and hold their breath before the examination. The scanning was initiated from the calcification score with a tube voltage of 120 kVp and a layer thickness of 3 mm. Scan range from 1–2 cm below the tracheal bifurcation to the diaphragmatic level of the heart. The retrospective ECG-gated coronary CTA scanning parameters were as follows: detector collimation, 192 × 0.6 mm; gantry rotation time, 0.25 s/r; pitch, 0.15; and slice, 0.75 mm. Automatic tube voltage technology  and intelligent tube current scanning technology  were used to automatically determine tube voltage and tube current, respectively. Based on the weight of the participants, a total of 30–60 mL of iopromide  was injected continuously into the median cubital vein at a rate of 2–4 mL/s, followed by an injection of saline solution. 20-phase images were reconstructed in 5% steps of the RR interval. The reconstruction parameters were as follows: thickness, 0.75 mm; the increment, 0.5 mm; reconstruction kernel, Bv40. The effective radiation dose was 4.9 ± 1.4 mSv, which was obtained by multiplying the dose-length product by 0.014.Eleven patients were randomly selected from the disease groups to undergo CMR using the 3.0 T system . They were repeatedly trained to inhale and hold their breath to ensure cooperation with commands during examination. A balanced steady-state free precession sequence and retrospective ECG gating were used to acquire left ventricular (LV) long-axis  and short-axis cine images covering the entire LV layer. The parameters were as follows: field of view, 340 mm × 287 mm, matrix, 256 × 216, repetition time/echo time, 34.2 ms/1.53 ms, reversal angle, 90°, and slice thickness, 8 mm.The best diastolic and systolic reconstruction images were imported into the postprocessing workstation , and coronary artery stenosis and CACs were analyzed by two experts with more than 10 years of experience in cardiovascular disease diagnosis. Obstructive CAD was defined as coronary CTA showing maximum diameter stenosis of ≥ 50% including groups III and IV. The disease groups were divided into 0 Agatston units (AU), 1–99 AU, 100–299 AU, and ≥ 300 AU according to the CACs. The commercial software  automatically calculated the following cardiac functional parameters using data of 20 phases per cardiac cycle: LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), stroke volume (SV), cardiac output (CO), LV ejection fraction (LVEF), global radial strain (GRS), circumferential strain (GCS), longitudinal strain (GLS). LV radial and circumferential strains were quantified on the short axis, whereas LV longitudinal strains were quantified on the long axis including 2-chambers, 3-chambers, 4-chambers and then averaged  was used to analyze all CMR images. Myocardial strain analysis was performed by manually outlining the endocardial and epicardial borders of the LV at the end-diastolic and end-systolic phases.A total of 16 samples were randomly selected, and myocardial strain was independently measured by two radiologists with more than 5 years of experience in cardiovascular disease diagnosis. Additionally, one observer measured myocardial strain after 2 weeks.1, the prevalence of CAD in adults was 5.6%. With a test level α of 0.05 and within a tolerance σ of 3%, the sample size was calculated on the formula: n = Z2α*P*(1−P)/σ2. The data were analyzed using Statistical Package for the Social Sciences Version 21.0. The normality of distributions for all continuous variables was assessed using the Shapiro–Wilk test. Continuous data with a normal distribution were expressed as x ± s, skewed data were expressed as median and upper and lower interquartile ranges, and categorical variables were expressed as frequencies (percentages). Differences between multiple groups were analyzed using one-way analysis of variance or the Kruskal–Wallis test. Additionally, Bonferroni and Tamhane’s methods were used for post hoc comparisons between two groups. Pearson’s and Spearman correlation coefficients were used to evaluate correlations between continuous variables as appropriate. Logistic regressions were used to analyze the effects of dichotomous variables. The Bland–Altman test was used to assess inter-method and intra- and inter-observer agreement. P-values of < 0.05 (two-tailed) were considered statistically significant.As reported in the previous literatureThe study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Tongji Medical College, Huazhong University of Science and Technology . All participants signed informed consent forms autonomously and voluntarily prior to participation.A total of 237 patients with basic clinical information and coronary CTA examination data were enrolled. 546 patients were excluded from the study population (arrhythmias (n = 43), valvular heart disease (n = 45), cardiomyopathy (n = 54), congenital heart disease n = 21), poor image quality (n = 35), a history of coronary artery reconstruction (n = 176), or insufficient clinical data (n = 172)). The general clinical characteristics and cardiac function parameters of each group are detailed in Table , poor imP < 0.01). As the CAD-RADS level increased, GRS, the absolute values of GCS (|GCS|), and GLS (|GLS|) gradually decreased. In CAD-RADS level 1, a significant decreased in |GLS| was observed in the three LV global myocardial strains. The GRS, |GCS|, and |GLS| were the smallest in group IV and differed significantly between the control group and groups I–III (P < 0.01). GRS was significantly lower in group III than in the control group and group I.The myocardial strain in patients with different CAD-RADS levels is shown in Table P < 0.01; Fig. P < 0.05).GRS, GCS, and GLS were found to be significantly correlated with CACs , LVEF , and GLS .The results of the univariate and multivariate logistic regression analysis of the obstructive CAD group and the baseline clinical characteristics are summarized in Table The Bland–Altman test was used for repeatability analysis between intra-observer and inter-observer agreement Fig. . Only 6.Figure The CAD-RADS level depends on the severity of coronary artery stenosis, which influences the decision-making for the appropriate treatment option for patients. We evaluated the differences in CT-derived myocardial strain in patients with different CAD-RADS levels and investigated the relationship between cardiac CT-based myocardial strain and the degree of CACs and coronary stenosis. The results revealed that LV global myocardial strain based on CT gradually decreased as the CAD-RADS level increased. A significant correlation was found between LV myocardial strain and CACs.15. The older the age and the higher the BMI, the greater the risk of CAD.We found significant differences in age, BMI, and CACs between groups. Age and BMI were greater in groups I–IV than that in the control group. Age is a non-adjustable risk factor for CAD, whereas obesity is a risk factor that can be adjusted by changing lifestyle habits16. An increased resting HR leads to an increase in the risk of cardiovascular diseases, and its effect on cardiovascular mortality is independent of other cardiovascular risk factors17. Several studies have shown that increased resting HR is positively correlated with cardiovascular mortality19. HR is the main determinant of myocardial oxygen consumption and coronary blood flow20. In CAD, HR is a relevant factor affecting myocardial oxygen balance; an increase in HR causes a decrease in oxygen supply and an increase in oxygen demand, thereby leading to myocardial ischemia, decreased myocardial elasticity, and reduced myocardial strain values. An experimental study21 has revealed that there is a close linear relationship between myocardial blood flow and systolic function and that a decrease in local blood flow causes a corresponding decrease in systolic function.Compared with the control group, the heart rate (HR) was higher in groups III and IV, whereas LV global myocardial strain values were lower. Generally, HR is a predictor of cardiovascular and all-cause mortality in patients with cardiovascular diseases22. When ventricular wall motion abnormalities cannot be visually detected in the early stages, a local myocardial strain may help detect subtle ischemia-induced changes in myocardial function. Longitudinal myocardial fibers are mainly located in the subendocardium, and longitudinal strain mainly reflects the contractile function of subendocardial fibers, which are most vulnerable to ischemia23.Significant differences were found in LVEF between group IV and the control group and in GLS between groups I–IV and the control group. A significantly decreased GLS was observed before a significantly decreased LVEF as the CAD-RADS level increased. LVEF represents the percent change in LV chamber size and determines the entire cardiac systolic function, with limited regional myocardial systolic function. Compared with LVEF, GLS is more sensitive in CAD, which can be used as an early sensitive marker of clinically asymptomatic and mild LV insufficiency24. Our study results were consistent with the findings of that study and showed that the absolute values of GRS, GLS, and GCS gradually decreased with an increase in the CAD-RADS level; this is because the coronary blood supply gradually decreases as the degree of coronary artery stenosis increases. This gradually leads to an imbalance in myocardial blood and oxygen supply and demand and the myocardium becoming ischemic, resulting in reduced myocardial elasticity and compliance and reduced myocardial strain values. Conversely, we evaluated LV global myocardial strain using the CAD-RADS classification, whereas the former study grouped patients according to intervals of 25% diameter stenosis. The variation of GRS in groups I and II and GCS within groups I–III were not statistically significant, suggesting that impaired LV short-axis motor function occurred later than long-axis function. In addition to the effect of myocardial fiber distribution, the radius of curvature of the circularly aligned middle layer fibers is smaller than that of the longitudinal fibers; thus, there is less myocardial stress and the appearance of functional abnormality is delayed24.A previous study reported that LV myocardial strain measured using three-dimensional speckle-tracking echocardiography (3D-STE) decreases to varying degrees with increasing coronary artery stenosis25, which demonstrates its predictive value for symptomatic/asymptomatic CAD27. Kerut et al. used coronary artery calcification for future CAD risk assessment and found that the likelihood of CAD events in patients was related to the total plaque load in the coronary arteries28. They also found a significant correlation between myocardial strain and CACs. The higher the CACs, the lower the absolute value of global myocardial strains. We found that CACS and strain parameters were mildly to moderately correlated. This may be due to the fact that the majority of patients prospectively collected had CACs ≤ 300. In the future, an equal sample of patients will be collected within different graded ranges of calcification scores to reduce bias. Greenland et al. discovered that the incidence of future CAD events will increase when the CACs is greater than 300 AU25. In the present study, GRS, |GCS|, and |GLS| in the group with a CACs of ≥ 300 AU were significantly decreased, which is consistent with the findings of Erasmo et al.29. The risk of CAD prevalence is closely related to the calcification score, and CACs of 100 AU and 400 AU are considered the thresholds that distinguish hemodynamically significant low and high-risk groups for CAD prevalence, respectively30. Our results showed that myocardial strain values tended to decrease with an increase in disease risk, which was significantly lower in the control group than in the disease groups. Compared with CACs of 0 in the control group, |GLS| in CACs of 0 in the disease groups was significantly decreased, suggesting that GLS may help detect subclinical LV dysfunction earlier than CACs. A retrospective study with a large sample showed that a calcification score of 0 was associated with a very low risk of experiencing a coronary event in the future, regardless of the number of coronary risk factors27. This may be because the presence of noncalcified plaque causes severe lumen stenosis, resulting in a high CAD-RAD grade in the disease group with a CAC of 0.CACs is an independent predictor of future cardiovascular events31. Our study revealed that age, LVEF, and GLS are independent risk factors for obstructive CAD. The risk of obstructive CAD increased by 6.7% for each year of age and by 15.6% and 26.1% for each unit increase in LVEF and GLS, respectively. The findings revealed that a decreased GLS can be an indicator of non-obstructive CAD32. Moreover, GLS assessed at rest was an independent predictor of significant CAD in patients with suspected stable angina (OR = 1.25)33. That means in patients with low- and intermediate-risk chest pain, the addition of resting GLS to exercise echocardiography and conventional echocardiographic indicators improves the prediction of severe CAD. Severe coronary artery obstruction can result in myocardial infarction and ultimately heart failure. A prospective study found that GLS was independently associated with the risk of heart failure occurrence in patients with CAD34. It provided increased prognostic value to standard markers in patients with CAD with preserved or decreased LVEF.The causes of INOCA include coronary microcirculation disorders, coronary artery spasms, and coronary artery coarctation. It lacks optimal treatment options in clinical practice. The present study showed a significant decrease in myocardial strain values of obstructive CAD, which is consistent with the results of a previous study14. Second, in the study, the mean heart rate was not statistically different between the groups, but few patients took beta-blockers when their heart rate was above 90 before performing the test, which may have affected the strain assessment. Third, to verify the consistency of CT and CMR, we randomly selected 11 patients for CMR examination. CMR was not performed on all patients because simultaneous examinations would likely add additional financial burden to patients and cause waste of medical resources. Finally, the study did not assess the regional LV myocardial strain in specific single coronary artery stenosis. However, studies related to single coronary lesions have been published by our team7. The focus of future research should be directed towards the application of CT-derived myocardial strain in the assessment of cardiomyopathy, as well as its potential to serve as a predictive tool for post-coronary revascularization outcomes.This study has some limitations. First, obstructive CAD was not verified by coronary angiography. Invasive exams are more appropriate for patients with severe stenosis or a history of myocardial infarction. None of our patients had a history of myocardial infarction. CTA was used to exclude coronary artery disease, and most patients showed mild to moderate stenosis, the guidelines recommend that functional evaluation should be used as a priority in this group of patientsIn conclusion, we found a mild to moderate correlation between myocardial strains and CACs. The LV global myocardial strain absolute values based on CT gradually decreased as the CAD-RADS level increased. Age, LVEF, and GLS were identified as independent risk factors for obstructive CAD.


Increased collagen content of the myocardium modifies tissue reflectivity and integrated backscatter (IBS) indexes are suggested as markers of myocardial fibrosis (MF). We sought to assess the correlation between calibrated (c) IBS and bidimensional (2D) strain derived IBS with left ventricular (LV) MF in patients with severe aortic stenosis (AS).2) AS and preserved left ventricular ejection fraction (60 ± 9%) were included. Basal septum cIBS was − 17.45 (–31.2–10.95) and − 9.17 ± 9.45dB from PLAX and A3C views, respectively. No significant correlations were found between IBS and both non-invasive CMR tissue characterization and CVF: median MF of 9.7(2.1–79.9)%. Acoustic indexes were not significantly different according to the presence of pre-operative LGE.We made a prospective observational cohort study including 157 patients with severe AS referred for surgical aortic valve replacement (AVR), with complete preoperative transthoracic echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) obtained from the anterior basal septum at the time of surgery. Two groups of 30 patients were specifically evaluated, with and without late gadolinium enhancement (LGE) at CMR. IBS was obtained at QRS peak from both parasternal long axis (PLAX) and apical-three-chamber (AP3C) views and measured in decibels (dB). Whole-cardiac cycle IBS at basal anterior septum was obtained from 2D longitudinal strain. Correlation analysis of reflectivity indexes was performed with global and segmental  values of native T1 and extracellular volume (ECV), and EMB collagen volume fraction (CVF) (Masson´s Trichrome). IBS values were compared in both group of patients (LGE + vs. LGE –). 60 patients  with high gradient (mean gradient: 63 ± 20mmHg), normal flow (45 ± 10mL/mIn this group of patients with classical severe AS, IBS reflectivity indexes are of no added value to discriminate the presence of MF.The online version contains supplementary material available at 10.1186/s12947-023-00311-x. Degenerative aortic stenosis (AS) is the most common valvular heart disease, characterized by the progressive narrowing of the aortic valve and concomitant left ventricular (LV) adaptation to chronic pressure overload . UltrastEndomyocardial biopsy (EMB) remains the gold standard method to assess cardiomyocyte adaptation and myocardium extracellular remodeling. Collagen volume fraction (CVF), as provided from histomorphometry analysis, is correlated with myocardial collagen content and is a recognized tool for the quantitative assessment of MF . HoweverCurrently, cardiac magnetic resonance (CMR) is progressing as the imaging modality of choice for the non-invasive detection and quantification of LV fibrosis in a wide range of clinical scenarios . It may Ancillary transthoracic echocardiography (TTE) studies tried to assess myocardial reflectivity properties by ultrasonic integrated backscatter (IBS) signal –14. As eHence, our aim was to assess the correlation between echocardiographic derived IBS and LV myocardial fibrosis in a group of patients with severe symptomatic AS, as evaluated by both non-invasive CMR and myocardial biopsy.From a cohort of 157 consecutive patients with severe symptomatic AS referred and accepted for aortic valve replacement (AVR) surgery at our tertiary centre between April 2019 and January 2022, we randomly selected 30 patients with and 30 patients without LV LGE at pre-operative CMR for the analysis in two groups, as specified in Supplementary Fig. Clinical parameters , 12-lead ECG and TTE were collected at study inclusion before AVR. CMR was performed within 2 weeks after patient inclusion alongside blood sample for haematocrit (Htc), creatinine, high-sensitivity cardiac troponin I (hsTnI) and N-terminal pro b-type natriuretic peptide (NT-proBNP). Both TTE and CMR studies were performed within 6 months before AVR. If clinically justified for coronary artery disease exclusion, patients performed a coronary angiography before intervention and coronary revascularization was added to AVR when indicated. Surgical myectomy was concomitantly performed if planned before intervention because of asymmetric septal hypertrophy or at surgeon´s discretion.All patients underwent a comprehensive TTE by experienced cardiologists before AVR, using commercially available ultrasound systems  with a 4D probe (3.5-MHz 2D phased array transducer), in accordance with current guidelines –22 Supp. ImagingAs previously described  and recoQanalysis and longitudinal strain imaging at AP3C view to obtain LV myocardial deformation curves and gather average whole-cardiac cycle absolute values of IBS at basal anterior septum (designated as strain-derived IBS)  Fig. B. Qanalyposition , 24.CMR study was performed at 1.5T equipment  using a clinical scan protocol, as previously published . MethodsFor the assessment of reflectivity indexes in both groups of patients, with and without LGE at CMR, we did not specifically perform the analysis according to the presence of LGE at the basal anterior septum. This would be supposed to be closer or coincident to the place of echocardiographic assessment. However, we suspected that this could limit the number of patients in the group with LGE.JTBaker®) for 24 to 48 h at room temperature (20ºC). Formalin fixed, paraffin  embedded tissues were processed in Sakura´s “Tissue-Tek VIP” and cut into 3 μm thick sections. Tissue section adhesion time and temperature were constant for one hour at 70ºC. Sections were stained with Masson´s trichrome for collagen/fibrosis assessment according to a standard protocol. Using a digital microscopic scanner  we obtained whole slide images (WSI), at a resolution of 0.5 μm. These were analysed at a dedicated algorithm specifically developed for brightfield images at the software platform QuPath 0.3.0. For quantification, dense endocardial fibrosis was excluded  or from complementary septal myectomy, performed by the surgical team at the time of surgical AVR. In a pre-analytical phase, biopsies were fixed in 10% neutral buffered formalin , or as median and interquartile range for variables with skewed distributions. Normal distribution was checked using Shapiro-Wilk test or skewness and kurtosis, as appropriate. Clinical characteristics of the subgroups of interest were compared using the χ2-test and Fisher’s exact test (when applicable) for dichotomous variables; and the student’s t-test or Mann-Whitney U test (when applicable) for continuous variables. Categorical variables were compared by two-tailed chi-square. Pearson or Spearman’s correlation coefficients were used to assess the correlation between global and segmental  values of native T1 and ECV, EMB CVF and cIBS within overall cohort and between each group. Inter and intra-observer variability for the quantification of reflectivity indexes was evaluated using Bland-Altman plots . This wap-value < 0.05 was considered statistically significant. The statistical analysis was performed with IBM SPSS Statistics 26.0 .A two-sided p < 0.001). Patients showed a median LGE mass of 3.0 g (0.0–23.8), exclusively with a mid-myocardial and/or junctional pattern. Median ECV values were within normal range. At EMB, all, except four of the cases, had appropriate endocardial inclusion. All types of myocardial fibrosis  were included for CVF quantification at the automatic algorithm. Pre-operative imaging and histopathology data are presented in Table A total of 60 patients with severe symptomatic AS and appropriate preoperative echocardiographic study, complete comprehensive CMR protocol and septal EMB performed at surgical AVR were included in this analysis. The median age of the patients was 74 [36-74] years, with female predominance (55%). These were all ambulatory patients, mostly with effort dyspnoea or functional impairment on daily activities. Overall clinical and laboratory data are summarized in Table .0 g 0.0–3.8, exclClinical and imaging data, including IBS indexes, in patients with and without LGE at preoperative CMR are depicted in Table At Bland-Altman plots, the mean difference of IBS measurements for the same observer was not statistically different. The results were similar for cIBS for both echocardiographic windows and strain derived IBS. Likewise, interobserver variability was negligible except for 2D strain derived mean IBS .cIBS values were significantly lower when calculated from AP3C view [–9.17 ± 9.45 vs. − 17.45 (–31.2–10.95), We were not able to detect significant correlations between IBS data, as assessed from distinct echocardiographic windows and methodologies, and distinct CMR tissue characterization parameters and CVF from histopathology Table , except We found no significant correlations between global and regional  longitudinal 2D strain and IBS indexes Table . Except The main findings of our study were that: (i) cIBS is not significantly different in patients with severe symptomatic AS according to the presence or absence of LGE; (ii) ultrasonic reflectivity indexes have neither relation to non-invasive markers of myocardial ultrastructural remodeling, as assessed by multi-parametric CMR, nor to CVF at EMB. In accordance with current clinical practice, where multimodality echocardiography is unable to provide direct markers of tissue composition, we found that IBS is of no added value to discriminate the presence of myocardial fibrosis in this setting.Despite our negative results, we are mostly in line with previous correlation studies, namely with those that investigate the usefulness of ultrasonic reflectivity indexes in patients with less than extensive grades of myocardial fibrosis . Older iTo further enhance the strength of a possible positive correlation of IBS with non-invasive markers, we quantified MF invasively at septal surgical EMB i.e., transaortic 0.5-10 mm sub valvular sample, making the same correlation analysis. As our quantification of MF at the gold-standard method is clearly less than extensive (median CVF below 10%), the lack of discriminatory power of IBS as a non-invasive method of fibrosis assessment in this cohort aligns with previous studies. Even so we should recognize that, particularly for segmental values of native T1 and ECV, conventional IBS estimation from a ROI sample at bidimensional echo images is probably not perfectly matching or representing the same area of the LV septum at CMR. Additionally, EMB not only involves endocardial tissue as it is also smaller than the 4 × 4 mm ROI dimension, positioned at the mid-septum. As said, dense subendocardial fibrosis was excluded from the quantification to counteract this issue and gather more mid-septum representativity. Finally, LGE quantification is for global LV replacement instead of histology derived MF, and this should be kept in mind for the correlation with IBS at a specific point of the interventricular septum. Strain derived IBS was neither related to non-invasive markers of myocardial structure nor to CVF, and this is probably related to the fact that cyclic variation of reflectivity is more a marker of contractility . Even soThe theoretical basis supporting the relation between myocardial tissue characterization and myocardial physical properties that define the interaction with ultrasonic waves may explain our results. Older studies have shown that collagen is a major determinant of echo intensity and ultrasonic backscatter expected to be sensitive to collagen type, postprocessing and organizational level . HoweverDespite being able to provide combined information towards valvular disease, global and regional LV function in patients with severe AS, echocardiography did not equally provide ultrastructural MF assessment by IBS. For more advanced LV disease stage in this setting, we might suppose that IBS may be of value in trying to identify patients with high fibrotic burden, eventually in some patients with preserved LVEF, whose prognosis would be deemed worse. As for myocardial strain, which is not capable to provide direct information towards ultrastructural composition, as also confirmed by our additional correlation, cyclic derived strain IBS was neither related to markers of fibrotic content.echomics signatures, as derived from reflectivity indexes, for non-invasive identification of MF at routine pre-operative echocardiography.EMB is both inappropriate and mainly feasible in already surgical referred patients, with sampling related limitations. On the other hand, CMR lacks echo´s availability, being expensive for the ever-increasing number of patients with severe AS. Hence, additional correlation studies are needed in trying to better assess IBS feasibility, reliability, and cut-off values for ultrastructural characterization. The final goal would be to develop ultrasound-based Technical details concerning IBS assessment are far from standardized. We were not able to use a defined protocol and we followed the measurements according to our echocardiographic equipment and post-processing software. For the sake of uniformization, we calibrated IBS for the pericardium to reduce the effects of distinct imaging setting such as depth, gain, compensation and temporal resolution, as recommended .Reflectivity indexes, except strain derived IBS, were acquired at QRS-peak to improve the acoustic signal from distinct myocardial scatters, as in theory these are better apart from each other during diastole. Contrary to previous data assessing the usefulness of IBS in patients with AS  we did nWe made this correlation analysis in a mostly uniform phenotype of patients with severe AS. Nevertheless, a control group of patients (non-severe AS and with no LV remodeling or dysfunction) could have been of value in trying to assess the possible distinct order of magnitude in terms of the acoustic measurements. In the same way, a group of patients with severe AS and extensive MF might have provided useful IBS cut-off values.Finally, the presence of disarray at histology might have interfered with the present results, as the orientation of the myocardial elements relative to the angle of insonation (anisotropic effect) should be considered for reflectivity properties .Integrated backscatter and derived indexes are unrelated to MF in symptomatic patients with severe AS referred for surgical AVR. As there is no correlation between IBS and both non-invasive markers of replacement and interstitial fibrosis and CVF at histopathology, reflectivity indexes are deemed not suitable for ultrastructural tissue characterization, at least in this group of patients with less than extensive grades of MF.Additional file 1. Supplemental methods.Additional file 2. Supplemental results.Additional file 3: Supplementary Figure 1. Study flow-chart depicting how both group of patients, with and without late gadolinium enhancement (LGE), were selected for the analysis. SAVR – surgical aortic valve replacement; TTE – transthoracic echocardiography; CMR – cardiac magnetic resonance; LV – left ventricular; IBS – integrated backscatter; I.V. – intra-venous; TAVR – transcatheter aortic valve replacement; EMB – endomyocardial biopsy. *two patients with small areas of subendocardial LGE – ischemic scars, with no previous history of ischemic cardiomyopathy. Supplementary Figure 2. Masson´s trichrome whole slide image for MF quantification. Endocardial delineation is depicted (dotted line) to exclude dense endocardial fibrosis before automatic algorithm quantification. Supplementary Figure 3. A) Detailed view with specific colour coded tissue components at automatic algorithm of quantification – white is fibrosis; B) Example of an automatic quantification table displaying absolute areas and proportion of each tissue components.Additional file 4: Supplemental Table 1. Spearman correlation analysis between GLS and basal interventricular septum longitudinal strain (ivs LS) and global and localized CMR tissue characterization parameters respectively. The correlation between ivs LS and collagen volume fraction at endomyocardial biopsy is also depicted. Abbreviations as in tables 1, 2, 3 and 4.


For critically ill patients, hemodynamic fluctuations can be life-threatening; this is particularly true for patients experiencing cardiac comorbidities. Patients may suffer from problems with heart contractility and rate, vascular tone, and intravascular volume, resulting in hemodynamic instability. Unsurprisingly, hemodynamic support provides a crucial and specific benefit during percutaneous ablation of ventricular tachycardia (VT). Mapping, understanding, and treating the arrhythmia during sustained VT without hemodynamic support is often infeasible due to patient hemodynamic collapse. Substrate mapping in sinus rhythm can be successful for VT ablation, but there are limitations to this approach. Patients with nonischemic cardiomyopathy may present for ablation without exhibiting useful endocardial and/or epicardial substrate-based ablation targets, either due to diffuse extent or a lack of identifiable substrate. This leaves activation mapping during ongoing VT as the only viable diagnostic strategy. By enhancing cardiac output, percutaneous left ventricular assist devices (pLVAD) may facilitate conditions for mapping that would otherwise be incompatible with survival. However, the optimal mean arterial pressure to maintain end-organ perfusion in presence of nonpulsatile flow remains unknown. Near infrared oxygenation monitoring during pLVAD support provides assessment of critical end-organ perfusion during VT, enabling successful mapping and ablation with the continual assurance of adequate brain oxygenation. This focused review provides practical use case scenarios for such an approach, which aims to allow mapping and ablation of ongoing VT while drastically reducing the risk of ischemic brain injury. Changes in hemodynamics can be life-threatening, particularly for critically ill patients. Patients with various medical conditions may suffer from difficulties with heart contractility and rate, vascular tone, and intravascular volume; these difficulties may result in hemodynamic instability, where adequate aerobic metabolism is not maintained , 2. ConsTraditional first line treatment for hemodynamic support includes vasopressor and inotropic drugs. While these methods are noninvasive, and typically result in increased blood pressure and CO, end-organ perfusion is often unreliable, and heart-related adverse effects can occur , 4. CounImpella is approved for use in cardiogenic shock; it has also been used in acute myocardial infarction complicated by cardiogenic shock, during high-risk percutaneous coronary intervention, cardiomyopathy with acute decompensation, postcardiotomy cardiogenic shock, off-pump coronary bypass, and more recently, ventricular tachycardia (VT) ablation , 7. ImpeHemodynamic support has a crucial and specific benefit when employed during percutaneous ablation of VT. Mapping, understanding, and treating the particular mechanism of the arrhythmia during sustained VT without support is often not feasible, as the vast majority of patients will experience hemodynamic collapse . ConsequAs mentioned, each form of MCS has its own hemodynamic benefits, limitations, and related complications. IABP provides a modest increase in CO, but at the expense of increased risk for vascular stroke injury and limb ischemia. VA-ECMO offers the greatest level of CO augmentation, but also risks vascular injury, limb ischemia, bleeding, sepsis, and embolism. Impella devices offer a range of CO levels and LV support but require a large arterial cannula and carry the highest risks for vascular injury . Further2 gap (P (v-a) CO2), where elevated (>6 mmHg) P (v-a) CO2 is an indicator of decreased systemic blood flow  use during VT ablation, including a higher complication rate due to the need for additional vascular access, continuous anticoagulation, and interference with electroanatomical mapping systems . A critiood flow . HoweverMore recently, noninvasive monitoring of cerebral tissue oxygen saturation by near-infrared spectroscopy (NIRS) has become more frequent, particularly in the context of Impella usage during VT ablation. VT is often unstable in patients in need of VT ablation, resulting in significant hemodynamic difficulties . ImpellaThe evidence supporting neuromonitoring for oxygen saturation is derived from numerous clinical arenas. In the cardiac surgery setting, monitoring and treatment of declining regional cerebral oxygen saturation prevented prolonged desaturations, correlated with reduced ICU visits and major organ morbidity and mortality , and may– In panel A, NIRS perfusion is measured on two separate channels, from which the tissue oxygenation index (TOI) is determined. Normal TOI values range from 60%–80%, and a drop of >20% from baseline values, or a value below 55%, may indicate poor oxygen delivery. Two 30 s VT episodes are simulated by rapid ventricular pacing (220 ms cycle length). During the first VT episode, Impella support is active, and only a moderate TOI drop is observed on both channels, with fast and complete recovery after cessation of VT. Conversely, during the second VT episode, Impella support is disabled and a profound drop in TOI is observed, taking 2 min to recover post-cessation of VT, and remaining unstable for an additional 2 min.– In panel B, arterial blood pressure curves and TOI collected at the onset of VT in a clinical case are presented. Typical nonpulsatile flow with overlap of systolic and diastolic curves is observed, offering very little guidance of what MAP values are acceptable for end organ perfusion.– Panel C shows TOI for this same VT onset, remaining within normal range with only minor drift from baseline, indicating adequate brain oxygenation during this part of the procedure.– Panel D shows a sudden deterioration of perfusion that was observed despite stable VT cycle length and pressure curves after more than 30 min of mapping, as evinced by the sharp drop of TOI after a reasonably horizontal phase . Simultaneous EEG monitoring revealed a near complete loss of electrical brain activity, indicating a loss of adequate brain oxygenation ; the VT was subsequently terminated by DC cardioversion (not shown). TOI recovery was near-immediate, but EEG monitoring demonstrated a burst suppression pattern  for several minutes after VT termination .As indicated above, pLVAD support is increasingly used in patients in need of VT ablation. Cerebral oximetric monitoring may serve as an “early warning” of decreased oxygen delivery to the brain. Percutaneous LVAD support is able to safely maintain end-organ perfusion even in the face of extended periods of hemodynamically unstable VT, enabling greater ability to execute entrainment and activation mapping. This translates into an improved hemodynamic profile, and avoidance of cerebral desaturation below a threshold of 55% . These oA 51-year-old woman with a VVI implantable cardiac defibrillator (ICD) for secondary prevention after an episode of sustained monomorphic VT presented with cardiac sarcoidosis and preserved LVEF. Magnetic resonance imaging (MRI) revealed a transmural left anterior and subepicardial late gadolinium enhancement. During the patient's first procedure, a bi-ventricular voltage map revealed normal endocardial substrate. However, sustained VT was not inducible despite an aggressive stimulation protocol and pharmacological autonomic tone modulation. After 3 months, a new episode of sustained monomorphic VT was terminated by ICD shock. With an endocardial and epicardial approach confirming normal voltage maps, sustained monomorphic VT (CL of 230 ms) was induced. During VT, a drop in arterial blood pressure and loss of CO was confirmed by NIRS neuromonitoring (NIRO-200NX monitoring system). As such, the VT was terminated by electrical cardioversion and an Impella 2.5 pLVAD was implanted to enable VT activation mapping. After pLVAD placement, cerebral perfusion was immediately repristinated and patient hemodynamics stabilized. Epicardial mapping revealed a focal (concentric) activation pattern and successful ablation of the VT was performed, resulting in VT termination during radiofrequency (RF) ablation and non-inducibility . There were no complications. The patient experienced an early recurrence during the first month but has since been recurrence-free for ≥2 years.A 68-year-old man with a cardiac resynchronization therapy device (CRT-D) implanted for primary prevention presented with non-ischemic dilated cardiomyopathy with reduced LVEF. The patient underwent an initial endocardial ablation for VT targeting late potentials, but experienced multiple recurrent VT events. A new procedure was performed with an endocardial and epicardial approach, with no circulatory support at case onset. Mapping revealed diffuse epicardial distribution of fragmented electrograms over both ventricles that was considered too extensive for substrate ablation. After VT induction, the patient showed hemodynamic instability and loss of CO. An Impella CP pLVAD was placed to allow VT activation mapping which showed a macro-reentry with critical conduction slowing over a modest region at the epicardial right ventricular outflow tract (RVOT). Ablation at this region was performed resulting in VT termination and the RVOT area was targeted for elimination of abnormal electrograms, after which non-inducibility was achieved. VT induction testing was guided by EEG and after VT termination, TOI recovery was near-immediate, though EEG monitoring often showed a few minutes of burst suppression pattern. A year post-procedure, the patient has not experienced any recurrence.A 64-year-old man with a CRT-D implanted for primary prevention presented with ischemic cardiomyopathy with reduced LVEF. The patient had two prior endocardial ablations and one endo-epicardial attempt due to recurrent VT storms with multiple ICD shocks. He was on a heart transplant waiting list due to lack of other options for arrhythmia control, despite a fairly good functional status classified as NYHA class 1 or 2. After referral for a second opinion, a new ablation was performed with an endocardial and epicardial approach with upfront Impella CP pLVAD circulatory support. Substrate mapping was performed followed by a VT induction protocol with burst pacing. The activation map revealed an endo-epicardial macro-reentry at the base of the LV, next to the mitral annulus. After ablation in this zone, other sustained VTs were still inducible, originating from the scar region of the LV ; these were also successfully ablated. Despite borderline MAP values, non-invasive neuromonitoring revealed sufficient end-organ perfusion throughout the procedure and eventually contributed to the procedural success .The key messages of this case series are that the presence of a pLVAD during ablation is a determining factor for procedural success, and that noninvasive neuromonitoring enables informed decision-making. Crucial factors for decisions regarding pLVAD placement were the absence of endo-epicardial substrate (patient 1), extensive substrate and impaired LVEF (patient 2), and the clinical history of multiple VT recurrences and presentation with VT storm (patient 3). Avoiding cerebral desaturation during prolonged periods of nonpulsatile flow reduced the risk of end-organ damage and contributed to a safer and more effective ablation. The presence of EEG also provided additional information that improved the assessment of complete brain recovery after VT termination.In the evolving landscape of pharmacological treatment for heart failure, more patients with ischemic, and even more so non-ischemic heart failure, are enjoying increased survival rates than ever before. These improvements have also challenged the existing VT ablation strategy of substrate mapping in sinus rhythm and have led to the identification of the limitations of this approach in the most challenging cases. These limitations present in cases where there is no identifiable useful substrate, where targeting the available substrate is not adequate for arrhythmia control, or where the substrate is too diffuse to make focal treatment by ablation a realistic option. In these scenarios, activation mapping may be considered, leveraging techniques and approaches used in supraventricular arrhythmias, provided the patient can be kept in a hemodynamic state that allows VT to exist long enough for detailed mapping. Mechanical circulatory support in the form of pLVADs can be introduced as needed during a procedure and provide enough support to make this approach realistic. Prompt identification of patients requiring prophylactic mechanical hemodynamic support may prevent periprocedural acute hemodynamic decompensation, which is associated with increased risk of mortality over follow-up . The PAIAll procedural indication assessments should involve input from a multidisciplinary team that includes an electrophysiologist, a heart failure specialist, and a cardiac intensivist. Subsequent decisions regarding appropriate procedural flow should involve the electrophysiologist, cardiac anesthetist, cardiac intensivist, and cardiac and vascular surgeons. The primary goal is to achieve patient weaning from the pLVAD at the end of procedure, except in cases where the patient presented as initially unstable, with pLVAD/ECMO already in place. Procedures should include closure of the access site with percutaneous devices, and as such, coordination with the surgical team is essential. Decisions regarding treatment and approach must consider patient stability and substrate conditions, as well as exclusion criteria and VT inducibility . SeveralConversely, some contraindications are relative, and may instead require additional procedures and/or tools to facilitate safe usage in these populations. Severe aortic regurgitation is one such contraindication, as the pLVAD mechanism increases aortic pressure, which can aggravate aortic insufficiency; this may lead to significant volume loading of the LV and result in dilatation. This may be counteracted with procedures such as surgical or transcatheter aortic valve replacement , 28, cenAs emphasized above, in daily practice, this decision flow should include input from a multidisciplinary team. This will ensure the ideal patient approach is evaluated and selected based on patient condition, comorbidities, and potential contraindications. Subsequent to VT mapping and ablation, patients should be weaned as soon as safely possible to restore native cardiac function. Weaning assessments should also involve multidisciplinary input throughout the weaning process, to ensure all necessary conditions are continually met. Cardiac power output is a key measure of intrinsic cardiac function and must be robust (>0.6 W), and pulsatility should be preserved after reduction or cessation of inotropic or vasopressor therapy . Tissue Combined NIRS and EEG monitoring in addition to pLVAD usage enables assessment of end-organ perfusion during VT, facilitating successful mapping and ablation. The use of pLVAD can be beneficial for all patients needing VT mapping and ablation, ameliorating the typically severe loss of CO, and neuromonitoring allows maintaining sufficient end-organ perfusion even in patients with impaired EF during long procedures. This may ultimately lead to successful VT ablation while drastically reducing the risk of ischemic brain injury.