Left Ventricular Remodeling Research Articles

Latent cytomegalovirus infection associates with impairments in myocardial reperfusion, left-ventricular function, and quality of life after ST-elevation myocardial infarction

Abstract Introduction Cytomegalovirus (CMV) is a ubiquitous herpesvirus affecting the majority of adults in European countries. CMV influences T-lymphocyte biology throughout life. We have previously associated CMV status with adverse left ventricular (LV) remodeling after ST-elevation myocardial infarction (STEMI) in a single-centre study. In this study, we aimed to assess the external validity of these findings. Methods This study is a retrospective analysis of 354 patients presenting with STEMI, who were recruited to A Trial of Low-Dose Adjunctive Alteplase During Primary PCI (T-TIME) and had blood samples archived. The participants underwent immediate coronary angiography and percutaneous coronary intervention (PCI), serial cardiovascular magnetic resonance (CMR) imaging at 2-7 days and 3 months post-STEMI, and serial assessment of health-related quality of life with the standardised EQ-5D visual analogue scale (VAS). CMV IgG titre was measured in cryopreserved samples from each patient, and patients were categorised as CMV negative, low-positive or high-positive. All analyses were adjusted for infarct location. Results Of 354 patients, 175 (49.4%) were CMV IgG titre negative, 89 (25.1%) were low-positive and 90 (25.4%) were high-positive. CMV+ patients were older (62.5 vs 58.7 years) and more likely to be non-White (6.7% vs 2.3%). CMV+ patients displayed several adverse outcomes. First, myocardial reperfusion was impaired. Thrombolysis in myocardial infarction (TIMI) flow grade 3 after PCI, indicating complete reperfusion, was less common in CMV+ patients (76.0% vs 84.6%; p=0.042). CMV+ patients also had a higher TIMI frame count after PCI (p=0.021), and non-significantly less ST-segment resolution at 60 minutes (38.8% vs 48.4%; p=0.066). Impaired myocardial reperfusion appeared to lead to impaired LV function, with LV ejection fraction (LVEF) measured on early CMR lower in CMV+ patients (42.6% vs 45.3%, p=0.004). At 3 months, LV function remained impaired in CMV+ patients (LVEF: 47.8% vs 49.7%; p=0.035). This was mirrored by CMV+ patients displaying higher NT-pro BNP levels at 2-7 days (1381 vs 1172pg/mL, p=0.097) and 3 months (575 vs 338pg/mL, p=0.021). Finally, impaired LV function appeared to affect quality of life. Over 3 months, in contrast to CMV-negative patients, those with the highest CMV IgG experienced almost no improvement in quality of life, measured by change in the EQ-5D VAS (negative: +9.93; high-positive: +0.70; p=0.0002). Conclusion CMV+ patients with STEMI experience worse outcomes, with impaired reperfusion, persistently reduced LV function and less improvement in health-related quality of life over 3 months. We hypothesise that the effect of CMV is mediated through immune activation. Future research should explore the mechanisms by which CMV-specific lymphocytes interact with myocardial reperfusion and repair post-STEMI.

Myocardial DNA damage is responsible for the relationship between genotype and treatment response in patients with dilated cardiomyopathy

Abstract Background Dilated cardiomyopathy (DCM) is one of the leading causes of heart transplantation. Our group and others have previously reported that DNA damage accumulation in myocardial tissue and certain genetic variants such as those in LMNA are associated with treatment response and prognosis (ref 1-5). However, the potential association between myocardial DNA damage and genotype, and their contribution when combined to predicting treatment response, remains unclear. Methods We identified the deleterious variants in cardiomyopathy-related genes by analyzing the whole exome sequencing data from 89 patients with DCM who were recruited from two participating facilities. Immunostaining of γ-H2A.X, a DNA damage marker, was performed on endomyocardial biopsy specimens from the same patients, from which the percentage of nuclei positive for γ-H2A.X signals (%γ-H2A.X) was calculated. Left ventricular reverse remodeling (LVRR) was assessed by transthoracic echocardiography at 1 year after biopsy. We examined the associations among genotype, myocardial DNA damage, and the achievement of LVRR. Results Among the 89 patients with DCM, 11 (12.4%) carried pathogenic or likely pathogenic (P/LP) variants in sarcomere genes such as TTN, and 21 (23.6%) carried P/LP variants in non-sarcomere genes such as LMNA, while the rest had no P/LP variants in cardiomyopathy-related genes (Figure A). Patients with P/LP variants in sarcomere genes had a lower %γ-H2A.X [21.2 (10.7–29.0)% vs. 7.0 (4.3–12.4)%, P = 0.002] (Figure B), and a higher probability to achieve LVRR at 1-year (81.8% vs. 23.8%, P = 0.003) (Figure C) when compared to those with P/LP variants in non-sarcomere genes. The odds ratio for carriers of P/LP variants in sarcomere genes to achieve LVRR was 14.40 (95%CI 2.31–89.94) compared to that for carriers of P/LP variants in non-sarcomere genes. However, this effect was markedly attenuated after adjusting for the proportion of γ-H2A.X-positive nuclei [adjusted odds ratio 6.05 (95%CI 0.86–42.53)] (Table). Conclusions Among patients with DCM, carriers of P/LP variants in sarcomere genes showed less DNA damage and a favorable treatment response, when compared with carriers of P/LP variants in non-sarcomere genes. Our results suggest that myocardial DNA damage was partially responsible for the relationship between genotype and treatment response in patients with DCM.Figure, panels A-C

Sex differences in severe aortic stenosis undergoing surgical replacement

Abstract Background Aortic stenosis (AS) is the most common valvular heart disease in developed countries. Sex differences have been described in AS pathophysiology and left ventricular (LV) remodelling, as well as clinical presentation and response to therapies (1). However, sex differences in LV function parameters, namely global longitudinal strain (GLS), have been scarcely explored so far. Purpose To investigate sex differences, taking into account GLS, in patients with severe AS referred to surgical aortic valve replacement (SAVR). Methods The study population was from a single centre, prospective registry of patients with severe native valve AS who were referred for SAVR between June 2020 to October 2022. Severe AS was defined by standard guideline criteria (2). All patients underwent an echocardiogram immediately before and at least 3 months after surgery. Results Table 1 recapitulates sex differences in our population (n=119, 43% women). No differences in age or cardiovascular (CV) risk factors were noted. Clinical presentation and AS etiology were also similar. At baseline, women had lower EuroSCORE (p=0.039), creatinine (p <0.001), and haemoglobin levels (p=0.001). The echocardiogram showed a higher mean aortic valve gradient in women (Gmean, 62 vs. 50 mmHg, p=0.002). Women also had higher relative wall thickness (RWT, 0.49 vs. 0.42, p=0.037), despite lower LV mass index (124.9 vs. 136.6 g/m², p=0.037). Regarding LV function, women showed higher EF (64% vs. 60%, p=0.002) and GLS (16.5% vs. 14.6%, p=0.006) values. This is partially explained by the higher prevalence of concomitant coronary artery disease (CAD) in men, more frequently subjected to a concomitant coronary artery bypass graft than women (CABG, 38% vs. 8%, p <0.001). Post-operative complications had similar rates in men and women. After a median follow-up of 16 (6-18) months, death from any cause (6.0% vs. 1.5%, p=0.186) and rehospitalization for CV causes (14.0% vs. 4.0%, p=0.055) tended to be more frequent among women. When considering patients with severe AS alone (n=89), women had higher Gmean (64 vs. 53 mmHg, p=0.035) and EF (65% vs. 62%, p=0.045) but similar GLS (16.9% vs. 16.6%, p=0.230) as compared to men (Figure 2). At follow-up, EF and GLS failed to improve in both sexes and no differences were noted between women and men (EF 60% vs. 60%, p=0.476; GLS 15.9% vs. 16.0%, p=0.976). Conclusions In a population of all-comers patients with severe AS undergoing SAVR, women showed higher Gmean, EF, and GLS values. This is partially due to the higher prevalence of a concomitant CAD in men. When considering patients with AS alone, women still had higher EF and Gmean than men, despite a similar GLS. Future larger prospective studies with longer follow-up are needed in order to further characterize such differences and correlate them with specific outcomes.

The dynamic increment of epicardial adipose tissue is associated with reverse remodeling after guideline-directed medical treatment in dilated cardiomyopathy patients

Abstract Background/Introduction Epicardial adipose tissue (EAT) accumulation is associated with adverse prognosis in patients with HFpEF and a better prognosis in HFrEF patients. Whether EAT is playing a protective role in dilated cardiomyopathy (DCM) patients have been described sparingly. Purpose Aim to explore whether the epicardial fat would change along with the dynamic changes in cardiac function and volumes after receiving guideline-directed medical therapy (GDMT) in patients with DCM. Methods We prospectively enrolled 232 DCM patients who underwent complete baseline and follow-up Cardiac magnetic resonance (CMR) examinations. The measurement of the epicardial fat composition includes epicardial fat thickness, paracardial fat thickness, and paracardial fat volume, while the measurement of body fat composition includes subcutaneous and visceral abdominal fat, while We used univariable and multivariable logistic regression to evaluate the association between different body and cardiac fat depots with the changes in bi-ventricular structure (delta indexed EDV) and function (delta EF). Results The study included 232 patients (mean age 46.1±14.1 years, 157 (67.7%) males). After GDMT, we found that the visceral fat thickness and EAT (thickness and volume) tend to significantly increase. The increase in the (left ventricular reverse remodeling) LVRR group was significantly higher compared with the non-LVRR group. Independently with the changes of BMI and body fat depots, the increment of EAT was associated with the improvement in bi-ventricular function and volumes (significantly positively correlated with the improvement of LVEF (r = 0.499, p < 0.001), and RVEF (r = 0.482, p < 0.001), negatively correlated with delta LVEDVi (r = -0.407, p < 0.001), delta RVEDVi (r = -0.305, p < 0.001)). Conclusions After GDMT, the increment of EAT was positively correlated with the improvement of bi-ventricular structure and function, independent of the changes in BMI and body fat depots.Graphic Abstract

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction

Abstract Background Heart failure (HF) with improved ejection fraction (EF, HFimpEF) gains increasing attention as a distinct HF subtype, characterized by left ventricular reverse remodeling and myocardial recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. Methods A total of 203 hospitalized HF patients with reduced EF (HFrEF, EF≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute EF improvement ≥10% and (2) a second EF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. Results During a median follow-up of 8.6 (4.9~13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (126.03 ± 57.71 cm3 vs 182.74 ± 82.99 cm3 , P< 0.001) and higher EAT density (-74.92 ± 6.84 HU vs -78.76 ± 6.28 HU, P< 0.001) both in ischemic and non-ischemic HF patients. EAT density was inversely correlated with EAT volume (r= -0.33, P< 0.001). Multivariate analysis showed lower EAT volume (OR: 0.881 [95% CI 0.821~0.939]) and higher density (OR: 2.354 [95% CI 1.314~4.415]) were both independently associated with the incidence of HFimpEF, after adjusting for conventional risk factors, pharmacological therapies and baseline anthropometric parameters including body mass index. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. Conclusions This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

Identification and validation of ventricular rhythmic risk subgroups in hypertrophic cardiomyopathy by clustering analysis including left ventricular strain analysis

Abstract Background The excess mortality in hypertrophic cardiomyopathy (HCM) patients is mainly attributed to the occurrence of ventricular arrhythmia (VA).The prediction of VA remains challenging and could be improved. Purpose The study aimed to characterize the VA risk profile in HCM patients through clustering analysis combining conventional parameters with information derived from left ventricular longitudinal strain analysis (LV-LS). Methods 434 HCM patients (65% men, mean age 56 years) were retrospectively included from two referral centers and followed longitudinally (mean duration 6 years). The validation cohort included 177 HCM patients from an other tertiary French center. Mechanical and temporal parameters were automatically extracted from the LV-LS segmental curves of each patient in addition to conventional clinical and imaging data. A total of 287 features were analyzed using a clustering approach (k-means). The first endpoint for VA included suspected SCD, aborted cardiac arrest, appropriate ICD therapy (AIT), sustained ventricular tachycardia (SVT) and non-sustained ventricular tachycardia (NSVT) during follow-up. Results From the derivation cohort, 4 clusters were identified with a higher rhythmic risk for clusters 1 and 4 (VA rates of 26%(28/108), 13%(13/97), 12%(14/120), and 31%(34/109) for cluster 1,2,3 and 4 respectively) (Figure 1). These 4 clusters differed mainly by the LV mechanics. Patients from cluster 4 had a severe and homogeneous decrease of myocardial deformation (global longitudinal strain (GLS) -11%, normal value ≥ -20%) associated with LV and left atrium (LA) remodeling (left atrial volume index (LAVI) 46.6 vs. 41.5 ml/m², p=0.04 and LVEF 59.7 vs. 66.3%, p < 0.001) and impaired exercise capacity (% predicted peak work 58.6 vs. 69.5%; p= 0.025). Patients from cluster 1 showed a marked deformation delay and temporal dispersion on the segmental analysis associated with a moderate decrease of the GLS (-15.3%; p <0.0001 for GLS comparison between clusters). Patients from clusters 2 and 3 had a small GLS decrease (GLS -17.2 and -16.3%, respectively) with a less severe phenotype for cluster 2 and older patients for cluster 3 (mean age 62.1 vs. 54.1 years; p < 0.0001). The clustering analysis in the validation population resulted in the creation of 4 clusters overlapping the derivation cohort with similar characteristics (Figure 2). Clusters 1’ and 4’ had a higher incidence of ventricular arrhythmia with a VA rate of 22%(5/23), 18%(16/88), 0%(0/17), and 20%(10/49) for clusters 1’,2’,3’ and 4’ respectively. Conclusion Machine-learning-based cluster analysis processing LV-LS parameters in HCM patients identified 4 clusters with specific LV-strain patterns and different rhythmic risk levels. In the future, the automatic extraction and analysis of LV strain parameters could help to improve the risk stratification for SCD in HCM patients.Clustering analysisExternal validation

Cardiovascular (reverse) remodelling induced by pregnancy: looking at the right side of the heart

Abstract Introduction Many studies have focused on pregnancy-induced left ventricular remodelling, overlooking the changes in right cardiac chambers. Purpose To characterize the right cardiovascular (CV) remodelling and reverse remodelling (RR) induced by pregnancy and postpartum, respectively, and the impact of CV risk (CVR) factors on these processes. Methods This prospective cohort was recruited at two tertiary centers from 2019 to 2022, including 51 healthy and 79 obese and/or hypertensive and/or with gestational diabetes and/or smoking habits pregnant women (cardiovascular risk [CVR] group). Women were evaluated by transthoracic echocardiography at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy, as well as one-month (PP1), six-months (PP2), and one-year postpartum (PP3). Generalized linear mixed-effects models were used for the analysis of right CV remodelling and RR and to evaluate the impact of CVR factors on these processes. Results This study included 130 pregnant women, 60.8% primiparous, with a median age of 33 years. Despite all echocardiographic results being within the normality range, we describe the progression of right heart adaptations throughout pregnancy and postpartum (Table 1), namely: 1) Similar enlargement of the right atrium (RA) and right ventricle (RV) dimensions throughout pregnancy, recovering at PP2 except for RA in the CVR group; 2) Preserved RV systolic function throughout pregnancy in both groups, while the postpartum hemodynamic normalization triggers a reduction of (TAPSE) and tricuspid S' wave velocity; 3) Reduced RA strain in both groups during pregnancy, more evident in CVR group, which had a slower postpartum recovery; 4) Preserved RV global longitudinal strain (GLS) throughout follow-up time, being significantly reduced in 3T of CVR group and recovering at PP2; 5) Reduction of tricuspid E/A ratio from 1T to 3T in both groups with an early recovery at PP1, being these values significantly higher in the healthy group, and 6) Steady pulmonary artery systolic pressure (PASP) values throughout follow-up time, showing consistently higher values in the CVR group. Conclusion This study describes the subclinical right cardiac functional and structural changes within the physiological range, which recover 6 months after delivery. CVR factors impact the magnitude of the subclinical RV diastolic function changes, PASP and myocardial deformation (strain) without any impact on classic RV systolic function.

TLR7 deficiency alleviated myocardial ischemia reperfusion injury via regulating macrophage-neutrophil interaction

Abstract Background Toll-like receptor 7 (TLR7) is an intracellular innate immune receptor activated by single-stranded RNA. We previously reported that TLR7 could recognize RNA from dying cardiac cells and thereby deteriorating post myocardial infarction left ventricular remodeling. However, its effect on myocardial ischemia reperfusion (IR) injury is still unknown. Purpose In this study, we aimed to investigate the role of TLR7 in myocardial IR injury and the underlying mechanisms. Methods C57BL/6J wild type (WT) and TLR7 deficient (TLR7-/-) mice underwent left anterior descending artery occlusion for 30min followed by reperfusion. Myocardial infarct size was measured by Evan’s blue and TTC staining. mRNA expression levels of cytokines and phagocytosis-related receptors were detected by qPCR. TUNEL assay was conducted to determine apoptosis in the heart. Influx of neutrophils and macrophages in ischemic myocardium was analyzed by flow cytometry and Histone Cit3 was imaged to examine formation of neutrophils extracellular traps (NETs), cardiac function was evaluated by echocardiography during post-IR injury follow-up. Results TLR7 expression was up-regulated after IR injury in ischemic myocardium of WT mice. Compared to WT mice, fewer apoptotic cells and smaller infarct size (34±2% vs. 23±3% of area at risk, p<0.01) were observed in TLR7-/- mice at 24 hours post-IR, which was accompanied by reduced inflammatory cytokines (IL-1β: 110.5±14.1 vs. 54.8±13.7, p<0.05; TNF-α: 4.6±1.0 vs. 2.0±0.4, p<0.05) and increased anti-inflammatory factors (TNF-β: 2.9±0.3 vs. 8.6±2.6, p<0.05; IL-10: 14.2±2.1 vs. 32.3±8.8, p<0.05). Surprisingly, although the influx of neutrophils and macrophages increased to a similar extent in WT and TLR7-/- mice, the latter exhibited remarkably less NETs formation and enhanced macrophage phagocytosis in the infarct region. Moreover, TLR7 deficiency improved cardiac function, as indicated by increased left ventricular ejection fraction (LVEF) and fraction shortening (FS) at 56d post-IR. Conclusions TLR7 deficiency alleviates myocardial IR injury and improves cardiac function probably via enhancing macrophage clearance of NETs in the injured myocardium.TLR7 deficiency in cardiac functionTLR7 deficiency decreased NETs formation

Valvular and myocardial fibroblast activation in aortic stenosis: a prospective positron emission tomography study

Abstract Introduction In patients with aortic stenosis, fibrosis is a common pathophysiological feature of leaflet thickening as well as left ventricular decompensation as it transitions from hypertrophy to heart failure. Valvular fibrosis can be quantified by contrast-enhanced computed tomography, and myocardial fibrosis by late gadolinium enhancement on magnetic resonance imaging, but neither can detect the activity of fibrosis and extracellular matrix remodelling. Gallium-68 Fibroblast Activation Protein Inhibitor (68Ga-FAPI) binds to activated fibroblasts, the key effector cell of fibrogenesis, and provides a measure of fibroblast activation and fibrosis activity. We aimed to measure fibrosis activity in the aortic valve and left ventricular myocardium of patients with aortic stenosis using 68Ga-FAPI uptake. Methods In a prospective observational cohort, patients with aortic stenosis and control subjects with normal aortic valves underwent transthoracic echocardiography, 68Ga-FAPI positron emission tomography, computed tomography, and magnetic resonance imaging. Valvular and myocardial 68Ga-FAPI uptake was quantified using the target-to-background ratio (TBRmax). Valvular non-calcific volume was quantified on computed tomography and replacement myocardial fibrosis was quantified by late gadolinium enhancement on magnetic resonance imaging. Results Fifty patients with aortic valve disease (9 with aortic sclerosis, and 7 with mild, 23 with moderate and 11 with severe aortic stenosis; 72±8 years, 70% male) and 4 control subjects (66±7 years, 50% male) participated. Increased 68Ga-FAPI uptake was observed in the aortic valves of patients with aortic sclerosis and stenosis and peaked in those with moderate disease (Figure 1). TBRmax of 68Ga-FAPI uptake correlated with the aortic valve non-calcific volume (r=0.354, p<0.05) on computed tomography. Thirty-one patients (62%) had myocardial 68Ga-FAPI uptake, of whom half (n=17; 34%) also had late gadolinium enhancement corresponding to the region of 68Ga-FAPI uptake (Figure 2). Myocardial 68Ga-FAPI uptake correlated with increased indexed left ventricular mass (r=0.333, p<0.05) and left ventricular wall thickness (r=0.385, p<0.05). Conclusions For the first time, we have identified both valvular and myocardial fibrosis activity in patients with aortic stenosis. Valvular fibroblast activation is increased in patients with aortic sclerosis and stenosis, peaking in patients with moderate disease and correlating with leaflet thickening. Myocardial fibroblast activation is seen in the majority of patients with aortic stenosis both in areas with and without established fibrosis, and is associated with indices of adverse left ventricular remodelling. Activated fibroblasts are thus an important potential treatment target in the valve and myocardium, with 68Ga-FAPI positron emission tomography holding major promise in better understanding the pathophysiology, progression and consequences of aortic stenosis.

Impact of microvascular resistance reserve on post-STEMI cardiac remodelling and diastolic function

Abstract Background Coronary microvascular dysfunction (CMD) is a common sequelae of ST-segment elevation myocardial infarction (STEMI), preventing adequate recovery of left ventricular (LV) perfusion. The interferences of con-commitment epicardial stenosis or hyperemic hemodynamic alterations limit traditional physiologic metrics. The microvascular resistance reserve (MRR) was developed to overcome these shortcomings. Purpose We aim to investigate the association between post-STEMI MRR, and the ensuing left ventricle (LV) diastolic dysfunction, and functional remodeling. Methods In this prospective, observational study, we enrolled STEMI patients with multivessel disease who successfully underwent primary percutaneous coronary intervention (PCI). At three months post-PCI, all patients received complete revascularization followed by coronary physiology assessment using the bolus thermodilution method to measure the fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR). MRR was calculated using the formula: MRR = (CFR/FFR) × (Pa rest/Pa hyper), where Pa rest and Pa hyper represent resting and hyperemic aortic pressure, respectively(1). CMD was defined as an MRR < 3.0 based on Boerhout et al(2). Diastolic dysfunction was defined according to the ASE 2016 guidelines. Functional LV remodelling (FLVR) was categorized according to Chimed et al(3). The relationship between CMD and the stages of FLVR and diastolic dysfunction was scrutinized over a 12-month follow-up period. Results We enrolled 210 patients, of whom 125 (59.5%) were men with a median age of 65 (IQR: 58–76). At the 3-month follow-up, the MRR was 3.46 (IQR 3.00, 3.92), with 56 (26.7%) patients having CMD (MRR<3.0). MRR is significantly correlated with the change of LVEF between primary PCI and 12 months (r=0.48, p<0.001, Fig1A). CMD patients have lower LVEF at 12 months (50.00% vs. 40.00%; p < 0.001) and demonstrated significantly less recovery in LV systolic function (-10.00% vs. 8.00%; p < 0.001, Fig 1B, 1C). CMD patients had a higher prevalence of grade 2 or 3 LV diastolic dysfunction (65.38% vs. 3.95%; p < 0.001, Fig 2A) and a higher incidence of advanced FLVR (Groups 3 and 4) compared to those without CMD (30.77% vs. vs. 10.53%; p < 0.001, Fig 2B). In multivariable logistic regression analysis, MRR was independently associated with LV diastolic dysfunction (0.17, 95%CI 0.08-0.33, p<0.001). Conclusions The novel parameter MRR is significantly related to LVEF recovery in STEMI patients and is an independent predictor for advanced LV diastolic dysfunction and FLVR. CMD patients, as diagnosed with MRR, showed a higher prevalence of advanced FLVR and diastolic dysfunction. These results suggest that MRR is a useful parameter for the identification and management of CMD in STEMI patients.

ECG as a screening tool for detection of significant functional mitral regurgitation in patients with left bundle branch block

Abstract Background Functional mitral regurgitation (FMR) may occur in the left bundle branch block (LBBB) due to mechanical left ventricular (LV) dyssynchrony, by the imbalance between the tethering and the closing forces exerted on the mitral apparatus1-3. Progressive FMR and LV remodeling result in a reciprocal worsening downward spiral and worse clinical outcomes1-3. Therefore, timely screening and follow-up of these patients to prevent the irreversible progression of FMR is required. To date, only LBBB morphology and QRS duration have been proven predictors of FMR4. Purpose This study aimed to assess the relationship between ECG parameters of LV dyssynchrony and the severity of FMR in patients with LBBB. Methods We retrospectively included 154 consecutive patients with LBBB, in sinus rhythm, who had an echocardiogram, with no more than mild organic valvular heart disease. We measured the following intraventricular dyssynchrony markers: LV activation times (LVAT), intrinsicoid deflection (ID) in lateral and aVF leads and a newly defined marker – the difference (Diff) between aVL and aVF ID’s (Diff_IDaVL_aVF). These two leads record the electrical activation of the two opposing myocardial segments adjacent to the posteromedial and anterolateral papillary muscles, respectively5 (Figure 1). Based on the severity of FMR, the patients were divided into two groups: no/mild FMR (grade II or less) (61%), and significant FMR (grade III and IV) (39%). Results In patients with significant FMR, the LVAT measured in lateral leads, the IDaVL and Diff_IDaVL_aVF were significantly longer, but IDaVF was significantly shorter compared to patients with no/mild FMR (p<0.001). Of all studied ECG parameters, the Diff_IDaVL_ aVF was the parameter that had the strongest correlation with significant FMR (r correlation coefficient 0.82, p < 0.001). In multivariable analysis the Diff_IDaVL_aVF (p = 0.010) was the only parameter independently correlated with significant FMR. On ROC analysis the best cut-off for significant FMR prediction was 55 ms (AUC of 0.99, sensitivity 90% and specificity 97%) (Figure 2). Conclusions In LBBB, a simple intraventricular dyssynchrony ECG parameter can provide insights into FMR severity. A 55 msec Diff_IDaVL_aVF identifies significant FMR that may benefit from early medical or CRT treatment to avoid progression and worse prognosis.

Identification of left ventricular flow features in healthy and pathological conditions

Abstract Background In the presence of mitral valve diseases or following surgical interventions, the hemodynamics in the left ventricle (LV) are significantly altered [1]. These maladaptive intraventricular hemodynamic alterations can stimulate a cascade of events leading to progressive adverse LV remodeling and eventual heart failure [2]. Qualitative and quantitative evaluation of LV flow features may provide a potential for sensitive risk stratification of clinical cardiac function [3]. Purpose The purpose of this study is to identifying LV flow features using in vitro experiments under both normal and pathological conditions, including mitral regurgitation (MR), mitral valve replacement with bioprosthetic/mechanical valve, and transcatheter mitral valve edge-to-edge repair (TEER). Methods We utilized a biohybrid approach to construct the in vitro experimental platform, where the native mitral valve (including chordae tendineae and papillary muscles) and aortic valve from porcine were combined with a 3D-printed silicon LV (figure 1). To ensure comparability across different conditions, we maintained consistency by utilizing the same native valve and 3D-printed LV. For pathological conditions, we cut the chordae tendineae in A2 zone to induce the severe degenerative MR, and TEER was performed on this prolapsed valve by placing two clips in A2-P2 zone. Then, the anterior leaflet of valve was cut, and a bioprosthetic valve and mechanical valve were sutured to mitral annulus to simulate surgical valve replacement, respectively. Left ventricular flow fields were measured using four-dimensional particle image velocimetry (4D-PIV) technique, with vector interval of 0.9 mm in all the spatial directions and temporal resolution of 10 ms. Results Significant differences in mean flow field were observed among healthy and pathological conditions (figure 2). Firstly, the vortex orientation was clockwise in healthy, MR, bioprosthetic valve replacement, and TEER conditions, which could accompany the redirection of blood flows towards the aortic valve. However, the replacement with a mechanical valve resulted in an alteration in vortex orientation from clockwise to counterclockwise. Secondly, the position of the center of the vortex changed in pathological conditions, with the center of the vortex closest to the apex and the left ventricle outflow tract in the healthy condition. Thirdly, the maximum Reynolds shear stress (RSS), which may be responsible for thrombus formation, significantly increased after TEER procedure and bioprosthetic valve replacement. Conclusions This study demonstrates significant changes in LV hemodynamics across different conditions. The flow features, including vortex orientations, vortex positions and the RSS, may potentially become crucial considerations for the optimization of artificial valves and mitral valve repair devices.Figure 1 Figure 2

Sinus rhythm maintenance and the changes of echocardiographic parameters in patients with late persistent atrial fibrillation at 6 months after direct current cardioversion

Abstract Background Late persistent non-valvular atrial fibrillation (AF), with a duration of its episode ≥90 days and up to 12 months, is considered a distinct persistent AF entity, which might possess substantial differences as compared to its early persistent pattern (up to 3 months) in terms of myocardial remodeling and its reversibility after cardioversion. Purpose To study the changes of echocardiographic parameters in patients with non-valvular late persistent AF with respect to sinus rhythm (SR) maintenance at 6 months after successful direct current cardioversion (DCCV). Methods The cohort single-center study enrolled 59 late persistent AF patients, who underwent a successful elective DCCV. At 6-months follow-up, patients were subdivided into the groups regarding SR maintenance: 32 (54 %%) patients with a maintained SR (G1), and 27 (46 %) patients with a failure to maintain SR (G2). The parameters of myocardial remodeling and function were evaluated by transthoracic (TTE) and transesophageal echocardiography (TEE) baseline (by TTE and TEE) and at 6-months follow-up (by TTE). Results TTE data from G1 patients, in contrast to G2, suggested better baseline status of left heart chambers, particularly the lower diameter of left atrium (LA), left ventricular (LV) end-diastolic and end-systolic volumes and higher LV systolic function (by LV ejection fraction [EF]). According to the TEE data, G2 (vs. G1) was characterized by more prevalent cases of LA spontaneous (echo) contrast (41 % vs. 15 %, respectively; p=0,042) and LA appendage flow velocity ≤40 cm/s (82 % vs. 53 %, respectively; p=0,022). At 6-months follow-up TTE, G1 patients, as opposed to G2, demonstrated a better profile of echocardiographic parameters, namely a lower LA diameter, LA and right atrium (RA) volumes, along with less advanced LV remodeling and higher LV EF. TTE data from G1 at 6-months follow-up after DCCV suggested the reverse remodeling of both atria, namely the decrease of LA diameter, LA volume and its index (Fig. 1), as well as RA volume and its index. Moreover, G2 demonstrated a decline in LV systolic function, in particular the rise of LV end-systolic volume and decrease of LV EF (Fig. 2), as compared to G1. Furthermore, at 6-months follow-up, G2 patients presented with more advanced severity of PH and tricuspid regurgitation, in comparison with G1. Conclusions Late persistent AF patients with a SR maintenance at 6-months follow-up after successful DCCV presented a better baseline profile of myocardial remodeling and systolic function. The SR maintenance at 6-months follow-up after DCCV was associated with the reverse remodeling of left heart chambers (LA and LV) and RA. On the contrary, a failure to maintain SR in late persistent AF patients was associated with a deterioration in LV systolic function, and more advanced PH and tricuspid regurgitation.

Prognostic impact of mitral valve geometry in patients with secondary mitral regurgitation: a secondary analysis of the MITRA-FR trial

Abstract Background Mitral valve (MV) transcatheter edge-to-edge repair (TEER) has emerged as a second line therapy on top of guidelines-directed medical treatment (GDMT) in heart failure (HF) patients with severe secondary mitral regurgitation (SMR). Following the disparate results of the COAPT and MITRA-FR pivotal trials, echocardiographic markers of LV remodeling and MR severity have been proposed to select patients most likely to benefit from MV-TEER. The characterization of MV geometry arises as a potential tool to stratify risk of outcomes in SMR patients, who underwent classical surgery or MV-TEER intervention. However, it remains unknown whether MV geometry parameters were associated with prognosis in MITRA-FR patients and whether MV-TEER could modulate their impact on outcomes. Purpose To evaluate the association between MV geometry and outcomes of HF patients with SMR in the MITRA-FR trial, as well as the impact of SMR treatment modality. Methods Thirteen MV geometry parameters were assessed from baseline transthoracic echocardiograms in patients from the MITRA-FR trial. The prognostic impact of MV geometry parameters was studied on top of the baseline clinical variables used in the primary analysis of MITRA-FR (i.e. age, atrial fibrillation [AF], ischemic cardiomyopathy, myocardial infarction, left ventricular ejection fraction [LVEF] and effective regurgitant orifice area [EROA]). The primary endpoint was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. The effect of treatment arms (MV-TEER plus GDMT vs. GDMT alone) on this association was also evaluated. Results Among the 307 patients included in the pivotal trial, 272 were analyzed in the present study (i.e. 135 from the GDMT group and 137 from the GDMT + MV-TEER group). Mean age was 70±10, 74% male. 50% had ischemic cardiomyopathy and 34% AF. LVEF was 33±7% and EROA was 31±11 mm². MV geometry parameters were presented for the whole population and according to the randomization group in the Table. Among these parameters, only MV tenting area remained independently associated with the primary endpoint (Hazard Ratio (HR) = 1.22 per 1 cm², Confidence Interval (CI) = 1.01-1.47; p=0.041) after multivariate analysis (Figure). Tenting height was independently associated with the risk of HFH (HR=1.07 per 1 mm, CI=1.00-1.14, p=0.037), but no MV geometry variable was associated with all-cause death. These findings remained consistent in both treatment arms (p>0.20 for interaction). Conclusion In HF patients with SMR included in the MITRA-FR trial, MV tenting area and MV tenting height were independently associated with the risk of HFH or all-cause mortality and HFH respectively, without any difference according to treatment arms. These data suggest that MV tethering provides an incremental prognostic value beyond classical echocardiographic variables, including EROA, and then should be considered in the risk stratification of patients with HF and SMR.Table of MV geometry parameters featuresMultivariate analysis (Forrest-plots)

A comparative analysis of conventional echocardiographic findings among different heart failure stages and phenotypes: insights from the national echocardiographic society registry

Abstract Background The contemporary conceptualization of heart failure (HF) encompasses four developmental stages (at risk for HF, pre-HF, symptomatic HF, and advanced HF) and three distinct HF phenotypes categorized by left ventricular ejection fraction (LVEF) (HFpEF, HFmrEF, HFrEF). However, there is a need for a more comprehensive understanding of echocardiographic similarities and differences among pre-HF stages and various HF phenotypes. Material and Methods Our national echocardiographic society conducted a multicenter HF screening initiative. General practitioners in 13 primary care centers utilized the original mobile phone app to determine referrals for transthoracic echocardiography and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing in individuals without a prior HF diagnosis. The 2021 ESC guidelines' algorithms were used to diagnose HF phenotypes and 2016 EACVI/ASA recommendation² to assess diastolic function. This study defined "heart stress" (elevated NT-proBNP in asymptomatic individuals with risk factors, regardless of structural heart disease or cardiac dysfunction) and "patients at risk for HF" (normal NTproBNP and at least one HF risk factor). All patients were categorized into six groups: (I) no HF, no risk, (II) at risk for HF, (III) heart stress, (IV) HFpEF, (V) HFmrEF, and (VI) HFrEF. Echocardiographic findings were compared among groups (II) to (VI), using ANOVA, Kruskal-Wallis and Chi-squared test, when needed. Results In a cohort of 930 outpatients (mean age 66±11 years, 61% female), 34.2% were diagnosed with HF, 22.3% experienced heart stress, 37.8% were at risk for HF, and 12.8% had neither HF nor risk factors (Figure). While NT pro BNP showed progressive increase, LVEF showed a progressive decline across the groups, reaching its lowest in HFrEF patients (Table). Simultaneously, left ventricular mass index (LVMi), left atrial volume index (LAVi), and maximal velocity of tricuspid regurgitation (TR Vmax) significantly increased in a stepwise manner. Variations in predominant LV geometry were significant across groups (p<0.001): normal LV geometry in those without HF (60.8%), concentric LV remodeling in at-risk patients (38.6%), normal LV geometry in heart stress (49%), concentric LV hypertrophy (LVH) in HFpEF (27.7%), eccentric LVH in HFmrEF (42.3%), and both concentric and eccentric LVH in HFrEF (43.3% each). Diastolic dysfunction increased prevalence across the groups (12.9% vs 24.7% vs 37.6% vs 19.6% vs 51.1%, p<0.001). Remarkably, HFmrEF group had the highest proportion of undetermined diastolic function (14.7% vs 23.1% vs 27.9% vs 50% vs 26.7%, p<0.001). Conclusions The mobile phone app used in primary care setting allowed identification of significant number of individuals in the pre-HF stages, warranting further investigation. Distinct echocardiographic differences in pre-HF stages and HF phenotypes provide valuable insights for early detection and tailored treatments.

Can haemodynamic force analysis be used to identify cancer treatment-related cardiac dysfunction? A comparison with strain and ejection fraction.

Abstract Background Haemodynamic Force Analysis (HDF) is an approach to quantification of intraventricular pressure gradients, from routine transthoracic echocardiography. HFA is potentially a sensitive means of assessing LV dysfunction, and has been used for the prediction of LV remodelling, but its use in the detection of subclinical LV dysfunction remains undefined. We sought whether HDF could be used to detect Cancer Treatment-Related Cardiac Dysfunction (CTRCD). Methods From a group of 240 pts undergoing echos at baseline and every 3 months in the course of potentially-cardiotoxic chemotherapy, we matched 28 pts who developed CTRCD with 33 controls. HDF was calculated by tracking the endocardial contour throughout the cardiac cycle (Figure). CTRCD was defined by the development of a 12% relative change in GLS, or an asymptomatic absolute EF change of 10% at 3, 6, 9 and 12 months. Results Of 28 pts developed CTRCD; 17 at 3 months, 5 at 6 months, 3 at 9 months and 3 at 12 months. At the time of developing CTRCD, there was a difference between absolute GLS (p-0.04) and borderline difference in EF (p=0.08). However, although there was a small difference in HDF between groups, the variance of this parameter was large, and the values were not significantly different (Table). There was no difference in total HDF (Table). Conclusions Although absolute levels of systolic HDF were different between pts with CTRCD and controls, the scatter of this parameter was large and no significant difference was documented. HDF may be better for predicting the evolution of abnormal LVs than ion the detection of subclinical dysfunction.

Sex differences related changes in cardiac structure and function after ST-segment elevation myocardial infarction

Abstract Background Sex disparities in presentation, treatment, and outcomes after ST-segment Elevation Myocardial Infarction (STEMI) are well recognized. However, little is known about sex related changes in cardiac structure and function following a STEMI in this contemporary era of early PCI. Purpose To compare sex differences in change of echocardiographic parameters of structure and function following a first-time STEMI. Methods This echocardiographic study involved 380 non-diabetic first-time STEMI patients. Structural and functional parameters were evaluated during initial hospitalization (median 1 day after presentation) and at 4-months. Adverse remodelling was defined as a 20% increase in left ventricular end-diastolic volume (LVEDV) at 4 months compared to the hospitalisation echo. Functional parameters included left ventricular ejection fraction (LVEF) and wall motion score index (WMSI). According to current guidelines, eccentric hypertrophy was defined as left ventricular mass index (LVMI) >95 g/m2 for women and >115 g/m2 for men with a relative wall thickness (RWT) ≤0.42; concentric hypertrophy was defined as LVMI >95 g/m2 for women and >115 g/m2 for men with RWT >0.42. The different patterns in geometry were assessed at 4-months. Results Among 380 patients, comprising 285 males and 95 females, females had a higher prevalence of hypertension (42% vs. 25.6%, p=0.004), lower hemoglobin levels (8.40 mmol/l vs. 9.10, p<0.001), and higher plasma NT-proBNP concentrations upon admission (132 ng/L vs 67, p<0.001) and after 24 hours (1322 ng/l vs 784, p<0.001). During the initial echocardiogram conducted upon hospitalization, as well as during the echocardiogram at 4 months, women had significantly lower LV diameters, LV volumes, LV mass, LAVI and wall thickness compared to man. However, during both evaluations women showed higher E/e’ ratio’s and LVEF. The change in echocardiographic variables between both timepoints did not differ significantly between sexes. Furthermore, no significant difference in LV geometry patterns (eccentric or concentric) were observed between sexes and adverse LV remodelling was similar between both groups at approximately 22-23% (p=0.991). Conclusions Although differences exist between sexes in patient characteristics and individual echocardiographic parameters, no disparity is observed in geometry patterns, adverse LV remodelling, or the change in echocardiographic parameters after STEMI.

Assessment of mechanical dyssynchrony can improve the new ESC-2021 guidelines for cardiac resynchronization therapy

Abstract Background In 2021, new guidelines for cardiac resynchronization therapy (CRT) were published by the European society of cardiology (ESC-2021), where the different classes of recommendations were based on a new ECG-based definition of left bundle branch block (LBBB). However, its association with reverse LV remodeling and additive prognostic value remain unknown. Aim To investigate (1) the association between the ESC-2021 CRT guidelines and reverse LV remodeling at follow up, and (2) the additive prognostic value of baseline assessment of mechanical dyssynchrony to the ESC-2021 guidelines. Methods We investigated 244 heart failure patients in sinus rhythm treated with CRT in two European centers. 70% of the population were males. Mean age was 69 ± 10 years, QRS duration: 154 ± 24 msec. Mechanical dyssynchrony at baseline was defined as the presence of apical rocking or septal flash (ApRock/SF) in 2D transthoracic echocardiography. LV volumes were measured at baseline and at 12 ± 6 months after CRT, where the amount of CRT induced reverse LV remodeling was calculated as the percent change of LVESV at follow-up compared to baseline. Results Applying the ESC-2021 LBBB definition, only 18% (n=45) of patients had LBBB. Applying the guidelines, only 14% (n=35) had class I recommendation (LBBB + QRS ≥ 150 msec), 44% (n=107) had class IIa (LBBB + QRS 130-149 msec or non-LBBB + QRS ≥ 150 msec), 29% (n=70) had class IIb (Non-LBBB + QRS 130-149 msec), and 13% (n = 33) were not recommended according to the ESC-2021 because of having baseline QRS duration between 120 and 129 msec. On the other hand, ApRock/SF was evident in 57% (n=140) of the patients. There was non-significant difference in the relative decrease in LVESV at follow up between patients with LBBB and non-LBBB applying the new LBBB definition (44% [IQR: 32-63], vs. 39%, IQR [20-57], P = 0.08, panel A). Similarly, there was no significant difference in the relative decrease in LVESV at CRT follow up among the four guideline recommendation classes, panel B. We combined presence of mechanical asynchrony at baseline with each of the guideline recommendation classes. The combination of ApRock/SF with classes IIa and IIb improved the prediction of reverse LV remodeling significantly (P<0.001 and <0.01 respectively), while adding mechanical asynchrony did not significantly improve prediction in the class I and the not-recommended subgroups. However, results of these last 2 may have been impacted by a small number of patients, panel C. Conclusion The new ESC-2021 definition of LBBB is associated with few patients with LBBB and consequently small number of patients with class I recommendation according to the new guidelines. There was weak association between the new ESC-2021 guideline classes of recommendation and reverse LV remodeling after CRT. However, baseline assessment of ApRock and SF can significantly improve the guidelines in predicting CRT outcome.

Clustering analysis based on clinically available data for improving risk stratification and outcome prediction of hypertension

Abstract Background Hypertension (HTN) is a heterogeneous condition with several factors contributing to adverse outcomes. Machine learning can harness complex data to unveil outcome predictors and guide prevention. Purpose To use clustering analysis on clinical data to identify HTN risk profiles and their associations with cardiovascular abnormalities and clinical outcomes. Methods A cohort of 14,840 UK Biobank hypertensive participants without pre-existing heart failure (HF) who underwent cardiovascular magnetic resonance (CMR) assessment was examined using K-means clustering on 79 clinical attributes. The clusters’ association with incident HF, mortality, atrial fibrillation (AF), and major adverse cardiovascular events (MACE) were evaluated, alongside imaging characteristics, with mediation analysis probing the role of imaging in risk differentiation. All post-hoc analyses were adjusted for vascular risk factors (VRFs), including diabetes, hypercholesterolaemia, previous myocardial infarction. Results Three distinct clusters differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles were identified. Cluster 1 (lowest risk), predominantly females, exhibited the most favourable metabolic profile and outcomes. Cluster 2 (highest risk), predominantly males, had the most adverse metabolic and cardiovascular profiles, and the highest risk of all adverse outcomes, especially AF and HF (hazard ratio (HR) 1.80 [1.45–2.25] and 1.85 [1.39–2.46]; p <0.005). This group was associated with more eccentric LV hypertrophy (LVH), overall poorer left atrial emptying function (LAEF), bi-ventricular systolic function and LV mechanics, and higher systemic vascular resistance (Figure 1). Cluster 3 (intermediate risk) was a more heterogeneous group with the highest burden of diabetes and adiposity and a moderate rise in AF and MACE risk (HR 1.61 [1.12-2.32] and 1.30 [1.07-1.58]; p <0.05). This cluster was associated with concentric LV remodelling and better indices of cardiac mechanics, but greater impairment in LA booster pump function (active LAEF) than Cluster 2 (Figure 1). Cluster 2's effect on MACE was mostly mediated through LV mass increase (proportion mediated, 67%), followed by changes (reducing) in LV global longitudinal strain (33%), and ejection fraction (25.4%). The indirect effect of CMR changes in the association between cluster 3 and MACE was much smaller with the highest proportion of the effects mediated through increased myocardial wall thickness (26%) but not LV mass, and changes in all the components of LA function. Conclusions Clinical data clustering provides insight into distinct HTN risk profiles, each with specific imaging characteristics and clinical trajectories, hinting at different pathophysiological mechanisms. Enhanced phenotyping can facilitate tailored interventions based on the disease subtype and improve clinical outcomes.Figure 1.

Left ventricular hypertrophy, wall thickness, and histological myocyte alteration in end-stage heart failure: a call for a standard definition

Abstract Objective This study aimed to examine the relationship between different left ventricular hypertrophy (LVH) classification criteria according to the American Society of Echocardiography (ASE), and anatomical measurement of LV wall thickness (LVWT) and histological evidence of myocyte hypertrophy. Methods Data from 146 consecutive patients (47 years; 75% were male) who have undergone heart transplantation were analysed. Fixed ventricles were dissected and measured in weight after both atria, great vessels, and epicardial fat were removed. The fixed biventricular weight was calculated as 87% of total weight (the effect of fixed formalin reduced the total weight by 3%). Anatomical LVWT was measured with a ruler at LV free wall where maximal thickness is located. A comprehensive echocardiogram was performed in all patients before heart transplantation. LVM and relative wall thickness (RWT) (2 PWT/LVEDD) were measured by M-mode echocardiography in parasternal long-axis view. Patients were considered to have LVH when the LVM index exceeds 95 g/m2 in women and exceeds 115 g/m2 in men. Patients were considered to have concentric LVH when RWT > 0.42. LVWT was measured using 2D echocardiography perpendicular to the LV long axis. Results Of 146 explanted hearts, dilated cardiomyopathy (CM), cardiac amyloid, and hypertrophic CM were diagnosed in 53 (47%), 1 (1%), and 8 (5%) patients, respectively. Anatomic ventricular mass correlated with echocardiographic LVM (r=0.5, p < 0.01). Anatomic LVWT modestly correlated with echocardiographic LVWT (r=0.2, p=0.01). Of 146 patients, echocardiographic normal LV geometry, concentric LV remodelling, concentric LVH, and eccentric LVH were present in 22 (15%), 6 (4%), 14 (10%), and 104 (71%), respectively. Increased LVWT (≥ 13 mm) assessed by 2-D echocardiography was present in normal LV geometry (5%), concentric LV remodelling (5%), concentric LVH (57%), and eccentric LVH (33%) (p <0.001) in those classified by ASE guidelines. Anatomic LVWT (≥ 13 mm) was present in normal LV geometry (14%), concentric LV remodelling 5%), concentric LVH (14%), and eccentric LVH (80%) (p <0.001) in those classified by ASE guidelines. Histological myocyte hypertrophy was present in normal LV geometry (12%), concentric LV remodelling (2%), concentric LVH (11%), and eccentric LVH (70%) (p <0.001) in those classified by ASE guidelines. Conclusions 2D-derived echocardiographic increased LVWT in patients with LVH defined by increased LVM index was present in approximately 30-50%. Furthermore, anatomical increased LVWT in those with LVH classified by ASE guidelines was present in a varying range of 10-70%. Patients with concentric LVH had a low prevalence of histological myocyte hypertrophy (approximately 10%). Inconsistencies in classification methods reveal the need for more robust LVH terminologies and definition that is consistent across cardiac imaging and anatomico-pathological examination, particularly in patients with CM.