Extent Of Myocardial Fibrosis Research Articles

Ethnicity Differences in Geometric Remodeling and Myocardial Composition in Hypertension unveiled by Cardiovascular Magnetic Resonance.

Hypertensive patients of African-ancestry (Afr-a) have higher incidences of heart failure and worse clinical outcomes than hypertensive patients of European-ancestry (Eu-a), yet the underlying mechanisms remain misunderstood. This study investigated right (RV) and left (LV) ventricular remodeling alongside myocardial tissue derangements between Afr-a and Eu-a hypertensives. Sixty-three Afr-a and forty-seven Eu-a hypertensives underwent multi-parametric cardiovascular-magnetic-resonance. Biventricular volumes, mass, function, mass/end-diastolic volume (M/V) ratios, T2- and pre/post-contrast T1-relaxation-times, synthetic-extracellular-volume (s-ECV) and myocardial fibrosis (MF) were measured. Three-dimensional shape modeling was implemented to delineate ventricular geometry.LV and RV-mass (indexed to body-surface-area) and M/V ratios were significantly greater in Afr-a than Eu-a hypertensives (67.1±21.7 vs. 58.3±16.7g/m2, 12.6±3.48 vs. 10.7±2.71g/m2, 0.79±0.21 vs. 0.70±0.14g/ml, 0.16±0.04 vs. 0.13±0.03g/ml, respectively; P<0.03) mirroring LV remodeling. Afr-a patients showed greater basal-interventricular-septum thickness than Eu-a patients, which may influence LV hypertrophy and RV cavity changes. This biventricular remodeling was associated with prolonged T2-relaxation-time (47.0±2.2 vs. 45.7±2.2ms, P=0.005) and higher prevalence (23% vs. 4%, P=0.001) and extent of MF (2.3[0.6-14.3] vs. 1.6[0.9-2.5] % of LV-mass, P=0.008) in Afr-a patients. Multivariable linear regression showed modifiable cardiovascular risk-factors and greater end-diastolic volume were independently associated with greater LV or RV-mass. Furthermore, ethnicity was independently associated with greater RV-mass, supporting our hypothesis of ethnic-specific hypertensive remodeling. Afr-a hypertensives had distinctive biventricular remodeling, including increased RV-mass and septal thickening, and subtle myocardial tissue abnormalities compared to Eu-a hypertensives. From this study, modifiable cardiovascular risk-factors, and ventricular geometry, but not ethnicity, were independently associated with higher LV mass.

Cardiac MRI in diagnosis, prognosis, and follow-up of hypertrophic cardiomyopathy in children: current perspectives.

Hypertrophic Cardiomyopathy (HCM) is an inherited myocardial disease characterised by left ventricular hypertrophy, which carries an increased risk of life-threatening arrhythmias and sudden cardiac death. The age of presentation and the underlying aetiology have a significant impact on the prognosis and quality of life of children with HCM, as childhood-onset HCM is associated with high mortality risk and poor long-term outcomes. Accurate cardiac assessment and identification of the HCM phenotype are therefore crucial to determine the diagnosis, prognostic stratification, and follow-up. Cardiac magnetic resonance (CMR) is a comprehensive evaluation tool capable of providing information on cardiac morphology and function, flow, perfusion, and tissue characterisation. CMR allows to detect subtle abnormalities in the myocardial composition and characterise the heterogeneous phenotypic expression of HCM. In particular, the detection of the degree and extent of myocardial fibrosis, using late-gadolinium enhanced sequences or parametric mapping, is unique for CMR and is of additional value in the clinical assessment and prognostic stratification of paediatric HCM patients. Additionally, childhood HCM can be progressive over time. The rate, timing, and degree of disease progression vary from one patient to the other, so close cardiac monitoring and serial follow-up throughout the life of the diagnosed patients is of paramount importance. In this review, an update of the use of CMR in childhood HCM is provided, focussing on its clinical role in diagnosis, prognosis, and serial follow-up.

Inflammation of conduction tissue is a major determinant of electrical instability in patients with arrhythmic phenotype of myocarditis

Abstract Background Arrhythmic presentation of myocarditis can be life-threatening although often associated with a preserved cardiac dimension and function. The involvement of conduction tissue (CT) has been suggested as pro-arrhythmic factor, but its role has not conclusively supported. Purpose CT inflammation in myocarditis with arrhythmic presentation. Methods We retrospectively enrolled consecutive patients from January 2010 to June 2021 with acute myocarditis (&amp;lt; 1 month from the onset of symptoms). Patients were categorized according to clinical presentation in arrhythmic [frequent premature ventricular beats, non-sustained or sustained ventricular tachycardia (VT) and survivors of ventricular fibrillation, associated to preserved cardiac contractility –LVEF ≥ 50%] (Group A) and cardiomyopathy phenotype (signs and symptoms of heart failure with LVEF≤ 45%) (Group B). All patients had a normal coronary network at angiography and an unremarkable valvular pattern at 2D-Echo.They all underwent a LV endomyocardial biopsy; sections of CT (Purkinje fibres) were identified by morphologic (Ashoff and Monkeberg criteria) findings and positive immunohistochemistry for HCN4. CT infiltration was demonstrated by the presence of CD45Ro+ T lymphocytes and the necrosis of adjacent small and loosely arranged myocytes. The extent of myocardial fibrosis, the rate of vasculitis and CT inflammation was compared between the two groups. Results Among 217 consecutive pts with biopsy-proven diagnosis of myocarditis, 107 (49.3%) had an arrhythmic presentation (Group A). CT was observed in 33 (30.8%) patients in the Group A and 31 (28.2%) of Group B. In patients with biopsy-evidence of CT, no significant difference was reported in the mean age (51.2±16.8 vs 53.7±14.7; p-value: 0.53) . Inflamed CT was documented in 2 (6.5%) cases in Group B and in 33 (100%) in Group A (p-value&amp;lt; 0.001). No statistically difference was observed between Group A and B regarding the presence of vasculitis (4 vs 1; p-value: 0.36) and myocardial fibrosis (8.8±4.2% vs 9.5±4.3%; p-value: 0.50). Conclusion CT inflammation is a major determinant of electrical instability in human myocarditis with arrhythmic presentation. Figure Legend Sustained ventricular tachycardia (A) associated to severe infiltration by CD45Ro T lymphocytes of CT in an acute myocarditis with arrhythmic presentation.

Abstract 15422: Diffuse Myocardial Fibrosis Predicts Outcome in Moderate and Asymptomatic Severe Aortic Stenosis

Introduction: Patients with moderate or asymptomatic severe aortic stenosis (AS) are at increased risk of cardiovascular events, but markers to guide intervention are lacking. We investigated the use of cardiovascular magnetic resonance (CMR) to identify drivers of outcome. Methods: Moderate (aortic valve area [AVA] 1.0-1.5 cm2) or asymptomatic severe AS patients (AVA≤1.0 cm2 and NYHA functional class I-II) (n=457) were prospectively enrolled from five international sites and parameters including extracellular volume fraction (ECV%) and late gadolinium enhancement were analyzed on CMR. Clinical events were defined as all-cause mortality and admission for heart failure. Results: Moderate AS patients had smaller left ventricular (LV) mass and less diastolic dysfunction compared to asymptomatic severe AS patients, but showed no difference in the extent of myocardial fibrosis and scar. During median 5.7-years follow-up, 83 clinical events occurred. Patients with clinical events had smaller AVA, greater diastolic dysfunction, and higher ECV% (median [interquartile range] ECV% 26.3% [24.3-29.8] vs 28.2% [25.5-30.8], P=0.003). There was a stepwise increase of clinical events across ECV tertiles. ECV% was associated with clinical outcome (adjusted HR 1.05, 95% CI 1.00–1.09, P=0.035), independent of AVA and aortic valve replacement as a time-dependent covariate. The prognostic significance of ECV% was consistent when AS severity was alternatively defined using aortic peak velocity and mean pressure gradient, and also across subgroups by AS severity and symptoms, AVA, aortic peak velocity, mean pressure gradient, and left ventricular ejection fraction (Figure). Conclusions: Increased diffuse myocardial fibrosis is associated with poor outcomes in moderate and asymptomatic severe AS patients and can help identify those who require closer surveillance and possibly earlier intervention.

The Depiction of Hypertension in Heart Imaging Examinations: An Up-to-Date Review of the Evidence.

Hypertension is one of the main preventable cardiovascular (CV) risk factors all over the years, closely related to CV morbidity and mortality. One of the most common hypertensive target organ damages is hypertensive heart disease (HHD), including left ventricular hypertrophy, which progresses gradually and leads to systolic or diastolic dysfunction of the left ventricular, and finally to end-stage heart failure. Regarding its prevalence and the need for early diagnosis, assessment of heart imaging examination is of major importance. Echocardiography has been used as the standard imaging technique to evaluate HHD for years, providing an accurate evaluation of the left ventricular geometry, along with the systolic and diastolic function. However, nowadays there is a growing interest in cardiovascular magnetic resonance (CMR). Despite the importance of the use of echocardiography in everyday clinical practice, numerous studies have shown the superiority of CMR as an imaging technique for clinical and research purposes, mainly due to its strength to provide an unlimited area of view, as well as the identification and quantification of the type and extent of myocardial fibrosis. Hence, this review aims to analyze the importance of heart imaging in the hypertensive population, with a special interest in CMR imaging.

Obesity enables NLRP3 activation and induces myocardial fibrosis via hyperacetylation of HADHa.

Obesity increases the risk of myocardial fibrosis, a pathological change in most heart diseases, but the mechanism has not been fully elucidated. Here, we found that mice with high-fat diet (HFD)-induced obesity had more severe myocardial fibrosis than control mice under normal and ischemia/reperfusion (I/R) conditions, which could be alleviated by neutralizing antibodies against interleukin (IL)-1β and IL-18, downstream products of the nucleotide-binding oligomerization-like receptor protein 3 (NLRP3) inflammasome, and the NLRP3 inhibitor MCC950. Mechanistically, mitochondrial hyperacetylation in obese mouse hearts recruited apoptosis-associated speck-like protein containing a CARD (ASC) to mitochondria and thus facilitated NLRP3 inflammasome assembly. Acetylation of K255 on hydroxyl-CoA dehydrogenase alpha subunit (HADHa) was identified to trigger the mitochondrial localization of ASC. Blockade of HADHa-K255 acetylation downregulated mitochondrial ASC, suppressed the NLRP3 inflammasome and attenuated post-I/R myocardial fibrosis in obese mouse hearts. In obese human patients, the extent of myocardial fibrosis according to T1 MRI was positively correlated with the plasma levels of IL-1β and IL-18, supporting the connection of NLRP3 inflammation to obesity-induced myocardial fibrosis. In conclusion, our study demonstrates that the heart is susceptible to fibrosis under obesity through hyperacetylated HADHa mediated activation of the NLRP3 inflammasome.

The Role of Multimodality Imaging in Pediatric Cardiomyopathies.

Cardiomyopathies are a heterogeneous group of myocardial diseases representing the first cause of heart transplantation in children. Diagnosing and classifying the different phenotypes can be challenging, particularly in this age group, where cardiomyopathies are often overlooked until the onset of severe symptoms. Cardiovascular imaging is crucial in the diagnostic pathway, from screening to classification and follow-up assessment. Several imaging modalities have been proven to be helpful in this field, with echocardiography undoubtedly representing the first imaging approach due to its low cost, lack of radiation, and wide availability. However, particularly in this clinical context, echocardiography may not be able to differentiate from cardiomyopathies with similar phenotypes and is often complemented with cardiovascular magnetic resonance. The latter allows a radiation-free differentiation between different phenotypes with unique myocardial tissue characterization, thus identifying the presence and extent of myocardial fibrosis. Nuclear imaging and computed tomography have a complementary role, although they are less used in daily clinical practice due to the concern related to the use of radiation in pediatric patients. However, these modalities may have some advantages in evaluating children with cardiomyopathies. This paper aims to review the strengths and limitations of each imaging modality in evaluating pediatric patients with suspected or known cardiomyopathies.

Cardiac imaging and biomarkers for assessing myocardial fibrosis in children with hypertrophic cardiomyopathy

Myocardial fibrosis, as diagnosed on cardiac magnetic resonance imaging (cMRI) by late gadolinium enhancement (LGE), is associated with adverse outcomes in adults with hypertrophic cardiomyopathy (HCM), but its prevalence and magnitude in children with HCM have not been established. We investigated: (1) the prevalence and extent of myocardial fibrosis as detected by LGE cMRI; (2) the agreement between echocardiographic and cMRI measurements of cardiac structure; and (3) whether serum concentrations of N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) and cardiac troponin-T are associated with cMRI measurements. A cross-section of children with HCM from 9 tertiary-care pediatric heart centers in the U.S. and Canada were enrolled in this prospective NHLBI study of cardiac biomarkers in pediatric cardiomyopathy (ClinicalTrials.gov Identifier: NCT01873976). The median age of the 67 participants was 13.8 years (range 1-18 years). Core laboratories analyzed echocardiographic and cMRI measurements, and serum biomarker concentrations. In 52 children with non-obstructive HCM undergoing cMRI, overall low levels of myocardial fibrosis with LGE >2% of left ventricular (LV) mass were detected in 37 (71%) (median %LGE, 9.0%; IQR: 6.0%, 13.0%; range, 0% to 57%). Echocardiographic and cMRI measurements of LV dimensions, LV mass, and interventricular septal thickness showed good agreement using the Bland-Altman method. NT-proBNP concentrations were strongly and positively associated with LV mass and interventricular septal thickness (P < .001), but not LGE. Low levels of myocardial fibrosis are common in pediatric patients with HCM seen at referral centers. Longitudinal studies of myocardial fibrosis and serum biomarkers are warranted to determine their predictive value for adverse outcomes in pediatric patients with HCM.

Association between left ventricular strain and fibrosis in severe aortic regurgitation with preserved ejection fraction: a magnetic resonance and histology study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Institutional Grant Na Homolce Hospital Background The presence and extent of myocardial fibrosis are associated with poor outcomes in patients with severe aortic regurgitation. In the present study, we tested a correlation between left ventricular (LV) strain derived by using feature-tracking cardiac magnetic resonance (MRI) and diffuse myocardial fibrosis percentage (DMF%) at quantitative histology. Methods A study population included 23 patients (age 51 ± 12 years, 78% males) who underwent perioperative myocardial biopsy during aortic valve surgery for severe aortic regurgitation and who had a satisfactory pre-surgery MRI. Myocardial specimens obtained with a deep needle technique from the basal interventricular septum were stained with picrosirius red, digitalized, and analyzed using Image J software by a pathologist blinded to imaging findings. The DMF% was calculated as a ratio of the total collagen content to the total area. MRI-derived global longitudinal-(GLS), circumferential- (GCS), and radial (GRS) strain, as well as their ratio to heart rate and systolic blood pressure, were assessed using a feature-tracking technique by a certified imager blinded to histological analysis. Results Compared to normal values, all patients showed increased DMF% (19 ± 9%) and decreased GLS (15 ± 2%) despite preserved LV ejection fraction (64 ± 7%). Out of all the imaging parameters, only GLS/heart rate ratio, GCS/heart rate ratio and extracellular volume fraction showed a significant correlation with DMF% (Table 1, Figure 1). In contrast, GLS and GCS only tended to correlate with DMF%. The remaining parameters including GRS did not show a significant association. Patients with focal midwall scar in late gadolinium enhancement imaging (n=8, 35%), which was mainly localized in the basal septum, had similar GLS as than patients without focal scar (14.5±2.3 vs 15.3±2.3, p = 0.768). Conclusions Feature-tracking-derived ratios of LV GLS and GCS over heart rate are the most promising indices for non-invasive assessment of diffuse myocardial fibrosis in severe aortic regurgitation with preserved ejection fraction. Figure 1 Legend Correlation of a GLS/HR ratio 1A) and GLS 1B) with diffuse myocardial fibrosis %. Myocardial histology stained with Picrosirius red (collagen fibers are in red).

Valvular Cardiomyopathy in Aortic Valve Regurgitation Correlates with Myocardial Fibrosis.

Objective: At the tissue level, disruption of the extracellular matrix network leads to irreversible cardiac fibrosis, which contributes to myocardial dysfunction. At the myocyte level, downregulation of beta-adrenoceptors (beta-AR) reduces adaptation to increased workload. The aim of our study was to analyse the correlation between myocardial fibrosis and beta-AR sensitivity in patients with aortic valve (AV) disease. Methods: A total of 92 consecutive patients who underwent elective AV surgery between 2017-2019 were included in our study (51 with aortic regurgitation (AR-group); 41 with aortic stenosis (AS-group) and left ventricular (LV) biopsies were obtained intraoperatively. In vitro force contractility testing was performed by measuring beta-AR sensitivity (-log EC50[ISO]). In parallel, a quantitative analysis of myocardial fibrosis burden was performed. Results: Mean age at the time of AV surgery was not statistically different in both groups (AR: 53.3 ± 15.3 years vs. AS: 58.7 ± 17.0 years; p = 0.116). The LV end-diastolic diameter was significantly enlarged in the AR-group when compared to the AS-group (59.4 ± 15.6 vs. 39.7 ± 21.2; p < 0.001). Analysis of beta-AR sensitivity (AR: -6.769 vs. AS: -6.659; p = 0.316) and myocardial fibrosis (AR: 8.9% vs. AS: 11.3%; p = 0.284) showed no significant differences between patients with AS and AR. There was no correlation between myocardial fibrosis and beta-AR sensitivity in the whole study cohort (R = 0.1987; p = 0.100) or in the AS-subgroup (R = 0.009; p = 0.960). However, significant correlation of fibrosis and beta-AR sensitivity was seen in AR-patients (R = 0.363; p = 0.023). Conclusion: More severe myocardial fibrosis was associated with reduced beta-AR sensitivity in patients presenting with AR but not with AS. Therefore, our results suggest that in patients with AR, cellular myocardial dysfunction is present and correlates with the extent of myocardial fibrosis in the myocardium.

Clinical Impact of Cardiac Fibrosis on Arrhythmia Recurrence after Ablation in Adults with Congenital Heart Disease

Adults with congenital heart disease (ACHD) are often affected by cardiac arrhythmias requiring catheter ablation. Catheter ablation in this setting represents the treatment of choice but is flawed by frequent recurrencies. Predictors of arrhythmia relapse have been identified, but the role of cardiac fibrosis in this setting has not been investigated. The aim of this study was to determine the role of the extension of cardiac fibrosis, detected by electroanatomical mapping, in predicting arrhythmia recurrencies after ablation in ACHD. Consecutive patients with congenital heart disease and atrial or ventricular arrhythmias undergoing catheter ablation were enrolled. An electroanatomical bipolar voltage map was performed during sinus rhythm in each patient and bipolar scar was assessed according to the current literature data. During follow-up, arrhythmia recurrences were recorded. The relationship between the extent of myocardial fibrosis and arrhythmia recurrence was assessed. Twenty patients underwent successful catheter ablation of atrial (14) or ventricular (6) arrhythmias, with no inducible arrhythmia at the end of the procedure. During a median follow-up period of 207 weeks (IQR 80 weeks), eight patients (40%; five atrial and three ventricular arrhythmias) had arrhythmia recurrence. Of the five patients undergoing a second ablation, four showed a new reentrant circuit, while one patient had a conduction gap across a previous ablation line. The extension of the bipolar scar area (HR 1.049, CI 1.011-1.089, p = 0.011) and the presence of a bipolar scar area >20 cm2 (HR 6.101, CI 1.147-32.442, p = 0.034) were identified as predictors of arrhythmia relapse. The extension of the bipolar scar area and the presence of a bipolar scar area >20 cm2 can predict arrhythmia relapse in ACHD undergoing catheter ablation of atrial and ventricular arrhythmias. Recurrent arrhythmias are often caused by circuits other than those previously ablated.

Diffuse Myocardial Fibrosis on Cardiac Magnetic Resonance Imaging Is Related to Galectin-3 and Predicts Outcome in Heart Failure.

Ongoing adverse remodeling is a hallmark of heart failure (HF), which might be reflected by either focal or diffuse myocardial fibrosis. Therefore, in (pre)clinical settings, we used immunohistochemistry or cardiac magnetic resonance imaging (CMR) to investigate the association of (focal or diffuse) fibrosis with cardiac biomarkers and adverse events in HF. In C57Bl/6J mice, we determined the presence and extent of myocardial fibrosis 6 weeks post-myocardial infarction (MI). Furthermore, we studied 159 outpatient HF patients who underwent CMR, and determined focal and diffuse fibrosis by late gadolinium enhancement (LGE) and post-contrast T1 time of the non-LGE myocardium, respectively. HF patients were categorized based on the presence of LGE, and by the median post-contrast T1 time. Kaplan-Meier and Cox regression analyses were used to determine the association of fibrosis with HF hospitalization and all-cause mortality. LGE was detected in 61 (38%) patients. Cardiac biomarker levels were comparable between LGE-positive and LGE-negative patients. LGE-positive patients with a short T1 time had elevated levels of both NT-proBNP and galectin-3 (1611 vs. 453 ng/L, p = 0.026 and 20 vs. 15 μg/L, p = 0.004, respectively). This was not observed in LGE-negative patients. Furthermore, a short T1 time in LGE-positive patients was associated with a higher risk of adverse events (log-rank p = 0.01). This study implies that cardiac biomarkers reflect active remodeling of the non-infarcted myocardium of patients with focal myocardial scarring. Diffuse fibrosis, in contrast to focal scarring, might have a higher prognostic value regarding adverse outcomes in HF patients.

Propionate alleviated post-infarction cardiac dysfunction by macrophage polarization in a rat model

The propionate (C3), the important components of short-chain fatty acids (SCFAs), had the effect of inhibiting pro-inflammatory macrophages. Earlier macrophages phenotypic transition from pro-inflammatory M1 to reparative M2 in early stage was a central juncture of cardiac dysfunction mitigation after myocardial infarction (MI). 160 Sprague-Dawley rats were assigned to 4 groups: sham group (n=40), sham+C3 group (n=40), MI group (n=40) and MI+C3 group (n=40). The rats in sham+C3 and MI+C3 group were treated with oral sodium propionate (200mM), and equivalent concentration of sodium chloride was administered in sham and MI group as control. After 7days of propionate adaptive feeding, rats were anesthetized and induced the MI by coronary occlusion. The classification of macrophages, the level of inflammatory factors and inflammatory signaling were estimated at 3rd days after thoracotomy, and the extent of myocardial fibrosis was evaluated at 7th and 28th days after operation. Echocardiography was estimated on 28th day after surgery. RAW264.7 cells, stimulated by LPS+IFN-γ with or without propionate, were harvested for western blot and supernatants were collected for cytokine analysis by ELISA. Propionate administration reduced the MI-induced myocardial fibrosis in infarcted border and attenuated cardiac function deterioration compared with MI group. In comparison with MI group, propionate promoted macrophages reduction, macrophage M2-like polarization, and inflammatory cytokines decrease in infarcted border zone following MI, which partly depends on the inhibition of JNK/P38/NFκB signaling pathways. Oral propionate in early stage, as a nutritional intervention, alleviated post-MI chronic cardiac remodeling and cardiac dysfunction at least in part by modulating macrophages polarization and pro-inflammatory cytokine, which were associated with reduction of JNK/P38/NFκB phosphorylation.

The frontal planar QRS/T angle in patients with non-ischemic type late gadolinium enhancement on cardiac magnetic resonance.

Evaluation of myocardial fibrosis may offer an insight into underlying pathological mechanisms of ventricular arrhythmias. We intended to investigate the possible association between the presence and extent of myocardial fibrosis and ventricular repolarization heterogeneity based on frontal planar QRS/T angle. We retrospectively investigated patients in whom gadolinium-based contrast agent cardiac magnetic resonance imaging was performed due to the suspicion of any myocardial disease. Patients with non-ischemic type late gadolinium enhancement (LGE) were enrolled into this study. The association between presence and extent of myocardial LGE and frontal planar QRS/T angle defined as the absolute difference between QRS wave axis and T-wave axis on a resting 12-lead surface ECG was evaluated. The frontal planar QRS/T angle was significantly higher in patients with myocardial fibrosis indicated by LGE compared to those without LGE (61.67 ± 40.70 vs. 37.27 ± 32.35, p < 0.001). LGE extent score assessed by visual 17-segment model was the only independent variable, which had a significant effect on frontal planar QRS/T angle [Unstandardized Coefficients B = 4.052, 95% CI [(2.025) - (6.079), p < 0.001]. In conclusion, this study showed that inhomogeneous areas of myocardium due to varying degrees of myocardial fibrosis might affect the electrical activity of the left ventricle, even with normal left ventricular dimensions and function.

Predictive value of cardiac magnetic resonance mechanical parameters for myocardial fibrosis in hypertrophic cardiomyopathy with preserved left ventricular ejection fraction.

Myocardial fibrosis leads to systolic dysfunction in hypertrophic cardiomyopathy (HCM) patients. This study aims to investigate the relationship between cardiac magnetic resonance mechanical parameters for evaluating the left ventricular function in HCM with preserved left ventricular ejection fraction (LVEF ≥50%) and the association between myocardial fibrosis defined by late gadolinium enhancement (LGE). This study was a retrospective analysis of CMR images of 93 patients with HCM with preserved ejection fraction (HCMpEF) and 96 controls diagnosed by cardiac magnetic resonance (CMR) at our hospital from July 2019 to January 2022. The myocardial contraction fraction (MCF) was calculated, and myocardial mechanical parameters, including global myocardial longitudinal strain (GLS), circumferential strain (GLS), and myocardial strain (GLS), were obtained by tissue tracking and LGE quantitative modules of dedicated software, respectively. The correlation between myocardial strain and LGE was analyzed, and a multivariate logistic regression model was developed to discuss the risk predictors of LGE. Compared to the control group, the left ventricular mechanical parameters GLS (-13.90 ± 3.80% versus -18.20 ± 2.10%, p < 0.001), GCS (-16.62 ± 3.50% versus -18.4 ± 2.69%, p < 0.001), GRS (28.99 ± 10.38% versus 33.02 ± 6.25%, p < 0.01), and MCF (64 ± 16% versus 99 ± 18%, p < 0.001) were found significantly lower in HCM group. Moreover, even in LGE-negative HCM patients, GLS (-16.3 ± 3.9%) and MCF (78 ± 19%) were significantly lower compared to the control group. Left ventricular GLS [OR = 1.61, (1.29, 2.02), p = 0.001] and MCF [OR = 0.90, (0.86, 0.94), p = 0.001] independently predicted myocardial late gadolinium enhancement (LGE). In participants of HCM with preserved ejection fraction, the early onset of reduced left ventricular GLS and MCF in patients with HCMpEF may provide new evidence for evaluating impaired myocardial systolic function. The reduction of myocardial mechanical indexes may reflect the presence and extent of myocardial fibrosis, and the more significant the reduction, the more severe the myocardial fibrosis; GLS and MCF may be ideal predictors for LGE.

Association between global longitudinal strain and myocardial fibrosis biomarkers in patients with end-stage chronic kidney disease

Abstract Introduction Myocardial fibrosis represents a landmark characteristic of uremic cardiomyopathy, leading to a high burden of arrhythmias, diastolic dysfunction (DD) and ultimately heart failure in this population. Collagen-derived biomarkers (Procollagen type I carboxy-terminal propeptide (PICP), Procollagen type III N-terminal peptide (P3NP)) and Galectin-3 (Gal-3) are associated with the extent of myocardial fibrosis on myocardial biopsy. Global longitudinal strain (GLS) as assessed by two-dimensional speckle tracking echocardiography (2D-STE) has been shown to detect subclinical myocardial dysfunction in various populations. The correlation between GLS and the serum level of these biomarkers has not been studied so far. Purpose The aim of this study was to evaluate the association between the left ventricular GLS measured by 2D-STE and the serum level of three biomarkers (PICP, P3NP, Gal-3) known to be associated with the presence of myocardial fibrosis, in patients with end-stage renal disease (ESRD), not on dialysis. Methods We conducted a cross-sectional study that included 135 patients with an eGFR (CKD-EPI) &amp;lt;15 ml/min/1.73 m2, stable, asymptomatic, not on dialysis. We performed a complete transthoracic echocardiography with 2D-STE and determined serum levels of PICP, P3NP and Gal-3 by ELISA. Patients in atrial fibrillation, with a permanent pacemaker or with a poor acoustic window were excluded. Results The mean age was 59.2±15.5 (median 61 years), 44% of the patients were males, 33% were diabetic, 11% had a history of myocardial infarction and 14% were smokers. The average volumetric ejection fraction (EF) was 54.4±9.8% (median 55%), with only 6.3% of the patients having an EF &amp;lt;40%. The majority of the patients (86.6%) had at least grade I DD, with only 5.3% having a restrictive pattern (grade III DD). The mean GLS was −16.8% ± 0.1 (median −17%). The average serum levels of PICP, P3NP and Gal-3 were 440.2±139.6, 244.9±380.1 and 10.8±6.7, respectively. After regression analysis, GLS was correlated with PICP, P3NP and Gal-3 levels (p=0.005, r=0.88; p=0.001, r=0.75; and p=0.006, r=0.81 respectively). Additionally, GLS was inversely correlated with the severity of DD (p=0.0001, r=0.84). In multiple regression analysis of a model consisting of GLS, PICP, P3NP and Gal-3, the serum level of PICP counted for 34% of the variance of GLS (R2=0.559, p=0.002, F=32.39). Conclusions In conclusion, this study proves that although stable and asymptomatic, patients with ESRD have lower values of GLS, a high proportion of DD and higher values of PICP, P3NP and Gal-3, when compared with the general population, in spite of a normal EF. Our study is the first to demonstrate that these biomarkers correlated with GLS in patients with ESRD, suggesting that GLS could represent an important tool for estimating the amount of fibrosis and risk stratification in this population. Funding Acknowledgement Type of funding sources: None.

Association of electrocardiographic markers with myocardial fibrosis as assessed by cardiac magnetic resonance in different clinical settings.

BACKGROUNDCardiac magnetic resonance (CMR) is a unique tool for non-invasive tissue characterization, especially for identifying fibrosis. AIMTo present the existing data regarding the association of electrocardiographic (ECG) markers with myocardial fibrosis identified by CMR - late gadolinium enhancement (LGE).METHODSA systematic search was performed for identifying the relevant studies in Medline and Cochrane databases through February 2021. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com).RESULTSA total of 32 studies were included. In hypertrophic cardiomyopathy (HCM), fragmented QRS (fQRS) is related to the presence and extent of myocardial fibrosis. fQRS and abnormal Q waves are associated with LGE in ischemic cardiomyopathy patients, while fQRS has also been related to fibrosis in myocarditis. Selvester score, abnormal Q waves, and notched QRS have also been associated with LGE. Repolarization abnormalities as reflected by increased Tp-Te, negative T-waves, and higher QT dispersion are related to myocardial fibrosis in HCM patients. In patients with Duchenne muscular dystrophy, a significant correlation between fQRS and the amount of myocardial fibrosis as assessed by LGE-CMR was observed. In atrial fibrillation patients, advanced inter-atrial block is defined as P-wave duration ≥ 120 ms, and biphasic morphology in inferior leads is related to left atrial fibrosis.CONCLUSIONMyocardial fibrosis, a reliable marker of prognosis in a broad spectrum of cardiovascular diseases, can be easily understood with an easily applicable ECG. However, more data is needed on a specific disease basis to study the association of ECG markers and myocardial fibrosis as depicted by CMR.

Therapeutic hypothermia alleviates myocardial ischaemia-reperfusion injury by inhibiting inflammation and fibrosis via the mediation of the SIRT3/NLRP3 signalling pathway.

Therapeutic hypothermia (TH) may attenuate myocardial ischaemia–reperfusion injury, thereby improving outcomes in acute myocardial infarction. However, the specific mechanism by which TH alleviates MIRI has not been elucidated so far. In this study, 120 healthy male Sprague‐Dawley rats were randomly divided into five groups. Haemodynamic parameters, myocardial infarction area, histological changes and the levels of cardiac enzymes, caspase‐1 and inflammatory cytokines were determined. In addition, the extent of myocardial fibrosis, the degree of cardiomyocyte apoptosis and the expression levels of SIRT3, GSDMD‐N, fibrosis‐related proteins and inflammation‐related proteins were estimated.TH reduced myocardial infarct area and cardiac enzyme levels, improved cardiomyopathic damage and haemodynamic indexes, and attenuated myocardial fibrosis, the protein expression levels of collagen I and III, myocardial apoptosis, the levels of inflammatory cytokines and inflammation‐related proteins. Notably, the immunofluorescence and protein expression levels of SIRT3 were upregulated in the 34H+DMSO group compared to the I/R group, but this protective effect was abolished by the SIRT3 inhibitor 3‐TYP. After administration of Mcc950, the reversal effects of 3‐TYP were significantly abolished, and TH could protect against MIRI in a rat isolated heart model by inhibiting inflammation and fibrosis. The SIRT3/NLRP3 signalling pathway is one of the most important signalling pathways in this regard.

Index of microcirculatory resistance in the assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy

Introduction and objectivesCoronary microvascular dysfunction (CMD) is one of the most important pathophysiological features in hypertrophic cardiomyopathy (HCM). The index of microcirculatory resistance (IMR) is an invasive method to assess the coronary microcirculation. The aim was to assess CMD in patients with HCM by IMR. MethodsAdult patients with HCM without epicardial coronary artery disease underwent cardiac catheterization for the assessment of CMD by IMR (normal cut-off value ≤22.0) and coronary flow reserve (CFR) (normal cut-off value ≥2). Cardiovascular magnetic resonance (CMR) was performed to assess the ischemic burden by perfusion imaging during regadenoson-induced hyperemia, and the extent of myocardial fibrosis was assessed by late gadolinium enhancement (LGE), native T1 mapping and extracellular volume (ECV). ResultsFourteen patients were enrolled with a mean age of 62.8±6.2years, 8 (57.1%) males, of whom 9 (64.3%) had obstructive HCM. Using IMR, CMD was detected in 4 (29%) patients. Among four patients with an IMR>22.0, all had non-obstructive HCM and two had angina. CFR<2 was reported in eight patients (57%). Concordance between IMR and CFR (both normal or both abnormal) was verified in 6 patients (43%). Among four patients with IMR>22.0, perfusion defects were found in two of the three patients who underwent stress CMR. Increased ECV (>28%) was documented in two of the patients with IMR>22 and in three of the patients with IMR≤22.0. LGE was >15% in 2 of the patients with IMR>22 and in 4 with IMR≤22.0. ConclusionsIMR assessment in HCM is feasible and safe. Patients with abnormal IMR seemed to have more significant tissue abnormalities on CMR.

Predictive Value of Echocardiographic Strain for Myocardial Fibrosis and Adverse Outcomes in Autoimmune Diseases

BackgroundMyocardial fibrosis is an important pathophysiologic mechanism of cardiac involvement that leads to increased mortality in patients with autoimmune diseases (AIDs). The aim of this study was to evaluate the association between myocardial strain from speckle-tracking echocardiography (STE) and fibrosis on cardiovascular magnetic resonance (CMR) and to further explore their prognostic implications in patients with AIDs.MethodsWe prospectively included 102 AIDs patients with clinically suspected cardiac involvement and 102 age- and sex-matched healthy individuals. Patients underwent CMR for evaluation of myocardial fibrosis by late gadolinium enhancement (LGE) and T1 mapping. A semiquantitative evaluation based on the extent of LGE was used to calculate the total (tLGEs) and segmental (sLGEs) LGE score. Global longitudinal strain (GLS) was evaluated by STE in all subjects. All patients were regularly followed up every 6 months. The primary endpoint was the composite incidence of all-cause death and cardiovascular hospitalization.ResultsCompared to healthy controls, AIDs patients had impaired GLS (−17.9 ± 5.1% vs. −21.2 ± 2.5%, p < 0.001). LGE was detected in 70% of patients. Patients with LGE presented worse GLS (−17.1 ± 5.3% vs. −19.6 ± 4.1%, p = 0.018) than those without LGE. On multivariate logistic analysis, GLS ≥ −15% was an independent predictor of LGE presence (OR = 4.98, 95%CI 1.35–18.33, p = 0.016). Moreover, a marked and stepwise impairment of segmental longitudinal strain (−19.3 ± 6.6 vs. −14.9 ± 6.5 vs. −8.9 ± 6.3, p < 0.001) was observed as sLGEs increased. During a median follow-up time of 25 months, 6 patients died, and 14 patients were hospitalized for cardiovascular reasons. Both GLS ≥ −15% (HR 3.56, 95%CI 1.28–9.86, p = 0.015) and tLGEs ≥ 6 (HR 4.13, 95%CI 1.43–11.92, p = 0.009) were independently associated with the primary endpoint.ConclusionsIn AIDs patients, impaired myocardial strain on STE could reflect the presence and extent of myocardial fibrosis and provide incremental prognostic value in addition to LGE in the prediction of adverse outcomes.