Remodeling In Aortic Stenosis Research Articles

Remodeling in Aortic Stenosis With Reduced and Preserved Ejection Fraction: Insight on Motion Abnormality Via 3D + Time Personalized LV Modeling in Cardiac MRI.

Increased afterload in aortic stenosis (AS) induces left ventricle (LV) remodeling to preserve a normal ejection fraction. This compensatory response can become maladaptive and manifest with motion abnormality. It is a clinical challenge to identify contractile and relaxation dysfunction during early subclinical stage to prevent irreversible deterioration. To evaluate the changes of regional wall dynamics in 3D + time domain as remodeling progresses in AS. Retrospective. A total of 31 AS patients with reduced and preserved ejection fraction (14 AS_rEF: 7 male, 66.5 [7.8] years old; 17 AS_pEF: 12 male, 67.0 [6.0] years old) and 15 healthy (6 male, 61.0 [7.0] years old). 1.5 T Magnetic resonance imaging/steady state free precession and late-gadolinium enhancement sequences. Individual LV models were reconstructed in 3D + time domain and motion metrics including wall thickening (TI), dyssynchrony index (DI), contraction rate (CR), and relaxation rate (RR) were automatically extracted and associated with the presence of scarring and remodeling. Shapiro-Wilk: data normality; Kruskal-Wallis: significant difference (P < 0.05); ICC and CV: variability; Mann-Whitney: effect size. AS_rEF group shows distinct deterioration of cardiac motions compared to AS_pEF and healthy groups (TIAS_rEF : 0.92 [0.85] mm, TIAS_pEF : 5.13 [1.99] mm, TIhealthy : 3.61 [1.09] mm, ES: 0.48-0.83; DIAS_rEF : 17.11 [7.89]%, DIAS_pEF : 6.39 [4.04]%, DIhealthy : 5.71 [1.87]%, ES: 0.32-0.85; CRAS_rEF : 8.69 [6.11] mm/second, CRAS_pEF : 16.48 [6.70] mm/second, CRhealthy : 10.82 [4.57] mm/second, ES: 0.29-0.60; RRAS_rEF : 8.45 [4.84] mm/second; RRAS_pEF : 13.49 [8.56] mm/second, RRhealthy : 9.31 [2.48] mm/second, ES: 0.14-0.43). The difference in the motion metrics between healthy and AS_pEF groups were insignificant (P-value = 0.16-0.72). AS_rEF group was dominated by eccentric hypertrophy (47.1%) with concomitant scarring. Conversely, AS_pEF group was dominated by concentric remodeling and hypertrophy (71.4%), which could demonstrate hyperkinesia with slight wall dyssynchrony than healthy. Dysfunction of LV mechanics corresponded to the presence of myocardial scarring (54.9% in AS), which reverted the compensatory mechanisms initiated and performed by LV remodeling. The proposed 3D + time modeling technique may distinguish regional motion abnormalities between AS_pEF, AS_rEF, and healthy cohorts, aiding clinical diagnosis and monitoring of AS progression. Subclinical myocardial dysfunction is evident in early AS despite of normal EF. 4 TECHNICAL EFFICACY: Stage 1.

Left Atrial Remodeling in Response to Aortic Valve Replacement: Pathophysiology and Myocardial Strain Analysis.

Severe aortic stenosis (AS) is the most common valve disease in the elderly and is associated with poor prognosis if treated only medically. AS causes chronic pressure overload, concentric left ventricular (LV) hypertrophy, myocardial stiffness, and diastolic dysfunction. This adverse remodeling also affects the left atrium (LA), which dilates and develops myocardial fibrosis, with a reduction in intrinsic function and a consequent high risk of the development of atrial fibrillation. Speckle-tracking echocardiography is able to detect myocardial dysfunction before other conventional parameters, such as LV ejection fraction, and also predict clinical outcomes. This review aims at describing LV and LA remodeling in AS and before and after aortic valve replacement and the usefulness of myocardial strain analysis in this clinical setting.

Proteoglycan remodelling in aortic stenosis

Proteoglycan remodelling in aortic stenosis

Characterisation of metabolic phenotype in aortic stenosis: insights from a multi-parametric cardiac magnetic resonance study

Abstract Introduction Left ventricular hypertrophy develops in Aortic stenosis (AS) as a result of increased afterload and is related to perturbations in cardiac fatty acid metabolism with evidence of steatosis and impaired myocardial energetics in severe AS. However, there is wide individual heterogeneity when it comes to degree of hypertrophy and progression to myocardial fibrosis and heart failure in those with same degree of stenosis. Underlying interplay of metabolism and hypertrophy may explain this variability. Purpose We sought to determine if a gradient of myocardial energetic impairment and steatosis exists across the spectrum of AS and precedes irreversible structural remodelling and subclinical LV dysfunction. We investigated metabolic remodelling in AS, focusing on its relationship with stenosis severity, degree of hypertrophy and fibrosis. Methods 74 AS participants including mild AS (n=18), asymptomatic moderate AS (n=38), asymptomatic severe AS (n=18), and healthy volunteers (n=13) underwent assessment of cardiac function, energetics (myocardial phosphocreatine to adenosine triphosphate ratio, PCr/ATP) and myocardial triglyceride content (MTG) using cardiovascular magnetic resonance (CMR) imaging and spectroscopy. Participants were divided into quartile groups based on their LV wall thickness (LVWT) and peak aortic valve gradient (AVG) to study relationship between cardiac metabolism and hemodynamic markers of LV structure and function. Results Baseline CMR characteristics (Fig. 1B-C) show a stepwise deterioration in LV structure and function across both the LVWT and AVG quartile groups (p values significant) with high LV mass index and relatively dilated LV as disease severity increases. Cardiac energetics (PCr/ATP]) were reduced in mild-moderate AS, Q2 (1.43±0.13 vs normal controls, Q1 1.80±0.14, p=0.05, Fig.2A) with a progressive decline with increasing AS severity (severe AS, Q4 PCr/ATP 1.39±0.14, p=0.02 vs controls). MTG was elevated in mild-moderate AS, Q2 (1.52±0.84 vs normal, Q1 1.25±0.70%, p=0.032, Fig. 2B). Whilst all AS groups had evidence of subclinical LV dysfunction with impaired strain parameters, impaired systolic longitudinal strain was related to the degree of energetic impairment (R 0.219, p 0.03). In addition, PCr/ATP was strongly associated with the presence of myocardial fibrosis (p 0.01) strengthening the hypothesis that metabolic changes may play a causative role in disease progression (Fig. 2C). Conclusion A gradient of myocardial energetic deficit and steatosis exists across the spectrum of hypertrophied AS hearts, notably we show in our study that these metabolic changes precede irreversible LV remodelling and subclinical dysfunction. These findings may have value for defining distinct metabolic phenotypes and identifying those most at risk of decompensation. This also opens another avenue for precision metabolic therapy in AS with a potential to intervene and delay or prevent decompensation. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship

DIFFERENCES IN RIGHT VENTRICULAR REMODELING AND ITS IMPACT ON SURVIVAL BETWEEN MEN AND WOMEN WITH AORTIC STENOSIS

Current guidelines recommends to treat tricuspid regurgitation/annulus dilation (TR/D) at the time of aortic valve replacement (AVR) for aortic stenosis (AS). However, sex-differences in TR/D and right ventricle (RV) remodeling in AS in patients with AS have not been investigated. We thus aimed to evaluated the sex-differences in TR/D, RV remodeling, as well as their importance on survival after AVR.

Pericardial NT-Pro-BNP and GDF-15 as Biomarkers of Atrial Fibrillation and Atrial Matrix Remodeling in Aortic Stenosis.

Aims: This study aimed to evaluate the association of GDF-15 and NT-pro-BNP in two different biological matrices with AF in severe aortic stenosis patients undergoing aortic valve replacement surgery (AVR), its association with atrial matrix remodeling, as well as with 30-day postoperative outcomes. Main Methods: One hundred and twenty-six patients between 2009 and 2019 with severe aortic stenosis undergoing AVR surgery in a tertiary hospital were assessed. Key Findings: pericardial fluid GDF-15 and pericardial fluid and serum NT-pro-BNP were increased in AF patients with aortic stenosis. COL1A1 and COL3A1 gene expression increased when pericardial fluid NT-pro-BNP values were higher. TIMP4 was positively correlated with pericardial fluid GDF-15. Significance: GDF-15 and NT-pro-BNP in the pericardial fluid are biomarkers of atrial fibrillation in aortic stenosis and correlate with atrial matrix remodeling. AKI is predicted by both serum and pericardial fluid GDF-15.

Chemokine receptor 5 antagonist, maraviroc, does not affect the progression of aortic stenosis in hypercholesterolemic mice

Background and Aims: In aortic stenosis (AS), valvular calcification causes the aortic valve dysfunction. Currently, no pharmacologic treatment is available for AS. Inflammation drives extracellular matrix remodeling in AS. Increased expression of inflammatory chemokines CCL3 and CCL4 have been detected in AS. CCL3 and CCL4 mediate their effects partly via CCR5-receptor. Thus, CCR5-receptor antagonist may prevent inflammatory response and decelerate the progression of AS. Here, we studied the effect of CCR5 antagonist, maraviroc, on AS in the hypercholesterolemic mouse model of AS.

Natural history of left ventricular remodelling in aortic stenosis treated by surgery: Differences according to sex

Many studies have shown differences between men and women regarding left ventricular remodelling in aortic stenosis with opposing results. Our aim is to see if women have a better preoperative and reverse remodelling in aortic stenosis. A comprehensive echocardiographic study of systolic, diastolic function and myocardial fibrosis was performed preoperatively, at 1 year and 3 years in patients undergoing surgical aortic valve replacement for aortic stenosis (± coronary artery bypass grafting). In total, 477 patients were included (200 women and 277 men). Women had a more concentric remodelling, a lower indexed left ventricular (LV) mass (103.7 ± 29.9 vs. 115.9 ± 29.3; P < 0.001), a higher left ventricular ejection fraction (LVEF) ( P = 65% vs. 61%, P = 0.01) and were more symptomatic at the time of surgery. One year after surgery ( n = 221, 95 women, 126 men), there was a regression in left ventricular mass (−23.5 g/m 2 in women, −18.0 g/m 2 in men), a better LVEF (+1.0 in women, +3.0 in men) and Global Longitudinal Strain. However, there was no statistically significative interaction of sex on the evolution of those parameters (for LV mass, interaction P = 0.12). Three years after surgery ( n = 91, 42 women, 49 men), there was a tendency to an interaction of sex on the evolution of the LV mass. Indeed, the regression was higher among women (interaction P = 0.066). It is of note that sex was independently associated in a multivariate model with LV mass reduction (expressed in percentage) ( P = 0.03). Despite a tendency, we have not showed any significant interaction of sex on the postoperative evolution of echocardiographic parameters regarding left ventricular remodelling in aortic stenosis treated by surgery. Nevertheless, sex was independently associated with LV mass reduction expressed in percentage.

LV replacement fibrosis in aortic stenosis: prevalence and relation to LV remodelling and function

Abstract Background Progressive myocardial fibrosis takes part in left ventricular (LV) remodeling in aortic stenosis (AS) and drives the transition from hypertrophy to heart failure. Replacement fibrosis may be characterized by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR). Aim To assess the prevalence and association between LGE and indexes of LV function in patients with severe aortic stenosis. Methods We prospectively studied 53 consecutive patients (age: 71±8 years [min. 51–max. 84], 54.7% men) with severe symptomatic AS, referred for surgical aortic valve replacement with no previous history of ischemic cardiomyopathy. Aortic valve mean gradient was 54.6 mmHg [IQR 46.6–63.2] and aortic valve area 0.74cm2 [IQR 0.61–0.89]; all patients with high gradient, 4 with low-flow. CMR with tissue characterization (T1 mapping, LGE and extracellular volume by ECV quantification – using 5SD from remote myocardium as signal intensity cut-off), was performed before surgery. AS severity indexes, LV mass, systolic and diastolic LV function indexes including global longitudinal strain (GLS) and torsion were compared in both groups of patients, with and without LGE. Results Mid-wall LGE was present in 36 patients (67.9%) with a median fraction of 6.0% [IQR 4.9–12.7%] of LV mass. Native T1 value and ECV were within normal ranges (median values: 1047ms [IQR 1028–1084]; 22% [IQR 18–25], respectively). Median CMR LV ejection fraction and mass were 64.5% [IQR 51.3–70.8%] (11 patients with reduced EF) and 76.5g/m2 [IQR 57.4–94.8g/m2], respectively. Median GLS was −13.9% [IQR −11.4 to −17.0%] and torsion was 24.2° [IQR 19.8–32.5°]. Patients with LGE had significantly higher LV mass (87.1g/m2 vs 63.3 g/m2, p=0.001), worse GLS (−14.4% vs −16.9%, p=0.041) and higher NT-proBNP values (1333.7ng/mL vs 559.9ng/mL, p=0.004) (Figure). Conclusions Non-ischemic LGE is common in this group of patients with severe symptomatic high gradient aortic stenosis. As it is more prevalent in patients with more pronounced LVH, lower longitudinal deformation and higher NT-proBNP values, it probably represents a more advanced stage of the disease. Funding Acknowledgement Type of funding source: None

Effect of Regional Upper Septal Hypertrophy on Echocardiographic Assessment of Left Ventricular Mass and Remodeling in Aortic Stenosis

Transthoracic echocardiography (TTE) is the reference method for evaluation of aortic stenosis (AS), and it is extensively used to quantitate left ventricular (LV) mass and volumes. Regional upper septal hypertrophy (USH) or septal bulge is a frequent finding in patients with AS and may lead to overestimation of LV mass when using linear measurements. The objective of this study was to compare estimates of LV mass obtained by two-dimensional transthoracic echocardiographic LV dimensions measured at different levels of the LV cavity with those obtained by cardiovascular magnetic resonance (CMR). One hundred six patients (mean age, 63±15years; 68% men) with AS were included in this subanalysis of the PROGRESSA study. Two-dimensional transthoracic echocardiographic measurements of LV dimensions were obtained at the basal level (BL; as recommended in guidelines), immediately below the septal bulge (BSB), and at a midventricular level (ML). Regional USH was defined as a basal interventricular septal thickness ≥ 13mm and >1.3 times the thickness of the septal wall at the ML. Agreement between transthoracic echocardiographic and CMR measures was evaluated using Bland-Altman analysis. The distribution of AS severity was mild in 23%, moderate in 57%, and severe in 20% of patients. Regional USH was present in 28 patients (26%). In the whole cohort, two-dimensional TTE overestimated LV mass (bias: BL,+60±31g; BSB,+59±32g; ML,+54±32g; P=.02). The biplane Simpson method slightly but significantly underestimated LV end-diastolic volume (bias -10±20mL, P<.001) compared with CMR. Overestimation of LV mass was more marked in patients with USH when measuring at the BL and was significantly lower when measuring LV dimensions at the ML (P<.025 vs BL and BSB). Two-dimensional TTE systematically overestimated LV mass and underestimated LV volumes compared with CMR. However, the bias between TTE and CMR was less important when measuring at the ML. Measurements at the BL as suggested in guidelines should be avoided, and measurements at the ML should be preferred in patients with AS, especially in those with USH.

MicroRNAs and ventricular remodeling in aortic stenosis

Introduction and ObjectivesSeveral mechanisms contribute to myocardial hypertrophy and fibrosis in aortic stenosis (AS). MicroRNAs are post-transcriptional modulators of such processes. We hypothesized that their expression in myocardial biopsies from patients with AS could be linked with the degree of left ventricular (LV) hypertrophy and remodeling and to plasma levels of important biomarkers of extracellular matrix turnover. MethodsWe performed myocardial biopsies in eleven patients with isolated severe AS undergoing aortic valve replacement. Echocardiographic exams and biomarker quantification were also performed. Five explanted hearts were used as controls for microRNA expression. ResultsOverexpression of microRNA-101-3p was found in AS, which correlated with higher levels of preoperative valvuloarterial impedance, angiotensin II receptor and angiotensin-converting enzyme, and LV mass regression after surgery. Although not differently expressed in AS compared to controls, both upregulation of miR-4268 and downregulation of microRNA-125-5p were associated with higher LV mass. MicroRNA-125b-5p correlated negatively with LV mass and with relative wall thickness at six-month follow-up. MicroRNA-4268 correlated positively with LV mass regression and was associated with higher plasma angiotensin II receptor levels. ConclusionsMicroRNA-101-3p and microRNA-4268 have potential new roles in the modulation of the hypertrophic response to AS via the renin-angiotensin-aldosterone system and as predictors of reverse remodeling after aortic valve replacement. Our results open new avenues in the understanding of myocardial response to pressure overload and of reverse remodeling after unloading. They also support the possibility of medical therapy to modulate the renin-angiotensin-aldosterone system in hypertrophic hearts.

MicroRNAs and ventricular remodeling in aortic stenosis

Several mechanisms contribute to myocardial hypertrophy and fibrosis in aortic stenosis (AS). MicroRNAs are post-transcriptional modulators of such processes. We hypothesized that their expression in myocardial biopsies from patients with AS could be linked with the degree of left ventricular (LV) hypertrophy and remodeling and to plasma levels of important biomarkers of extracellular matrix turnover. We performed myocardial biopsies in eleven patients with isolated severe AS undergoing aortic valve replacement. Echocardiographic exams and biomarker quantification were also performed. Five explanted hearts were used as controls for microRNA expression. Overexpression of microRNA-101-3p was found in AS, which correlated with higher levels of preoperative valvuloarterial impedance, angiotensin II receptor and angiotensin-converting enzyme, and LV mass regression after surgery. Although not differently expressed in AS compared to controls, both upregulation of miR-4268 and downregulation of microRNA-125-5p were associated with higher LV mass. MicroRNA-125b-5p correlated negatively with LV mass and with relative wall thickness at six-month follow-up. MicroRNA-4268 correlated positively with LV mass regression and was associated with higher plasma angiotensin II receptor levels. MicroRNA-101-3p and microRNA-4268 have potential new roles in the modulation of the hypertrophic response to AS via the renin-angiotensin-aldosterone system and as predictors of reverse remodeling after aortic valve replacement. Our results open new avenues in the understanding of myocardial response to pressure overload and of reverse remodeling after unloading. They also support the possibility of medical therapy to modulate the renin-angiotensin-aldosterone system in hypertrophic hearts. Numerosos mecanismos contribuem para hipertrofia e fibrose miocárdica em doentes com estenose aórtica (EA), incluindo modulação pós-transcripcional por microARNs. Levantamos a hipótese da sua expressão em biópsias miocárdicas de doentes com EA relacionar-se com o grau de hipertrofia ventricular esquerda e processos de remodelagem ventricular, bem como com níveis plasmáticos de biomarcadores importantes de turnover da matriz extracelular. Realizamos biópsias miocárdicas em 11 doentes com EA grave isolada referenciados para substituição valvular. Executamos também ecocardiografia e quantificação de biomarcadores. Cinco corações explantados foram usados como controlo da expressão dos microARNs. Descobrimos uma sobre-expressão do microARN-101-3p em doentes com EA que se correlaciona com níveis mais elevados pré-operatórios de impedância valvuloarterial, recetor tipo 2 da angiotensina (AT2), enzima conversora da angiotensina e regressão da massa ventricular esquerda (MVE) pós-cirurgia. Apesar de não significativamente diferentes entre grupos, descobrimos que sobrerregulação do microARN-4268 e sub-regulação do microARN-125b-5p estão associadas a maior MVE pré-operatória. O microARN-125-5p correlaciona-se negativamente com a MVE indexada e com a espessura relativa da parede aos seis meses de seguimento. O microRNA-4268 correlaciona-se positivamente com a regressão da MVE e associa-se a níveis mais elevados do recetor AT2. Os microARN-101-3p e microARN-4268, via sistema renina-angiotensina-aldosterona, têm potencial novo papel na modulação hipertrófica na EA e como preditores de remodelagem reversa pós-cirurgia. Estes resultados auxiliam na compreensão da resposta miocárdica à sobrecarga de pressão e da remodelagem reversa após diminuição da carga. Suportam também a hipótese de modulação farmacológica do sistema renina-angiotensina-aldosterona em corações hipertróficos.

Prognostic value of myocardial fibrosis in severe aortic stenosis: study protocol for a prospective observational multi-center study (FIB-AS)

BackgroundAdverse cardiac remodeling with a myocardial fibrosis as a key pathophysiologic component may be associated to worse survival in aortic stenosis (AS) patients. Therefore, with the application of advanced cardiac imaging we aim to investigate left ventricular myocardial fibrosis in severe AS patients undergoing aortic valve replacement (AVR) and determine its impact with post-intervention clinical outcomes.MethodsIn a prospective, observational, cohort study patients with severe AS scheduled either for surgical or transcatheter AVR will be recruited from two tertiary heart centers in Denmark and Lithuania. All patients will receive standard of care in accordance with the current guidelines and will undergo additional imaging testing before and after AVR: echocardiography with deformation analysis and cardiovascular magnetic resonance (CMR) with T1 parametric mapping. Those undergoing surgical AVR will also have a myocardial biopsy sampled at the time of a surgery for histological validation. Patients will be recruited over a 2-year period and followed up to 2 years to ascertain clinical outcomes. Follow-up CMR will be performed 12 months following AVR, and echocardiography with deformation analysis will be performed 3, 12, and 24 months following AVR. The study primary outcome is a composite of all-cause mortality and major adverse cardiovascular events.DiscussionDespite continuous effort of research community there is still a lack of early predictors of left ventricular decompensation in AS, which could improve patient risk stratification and guide the optimal timing for aortic valve intervention, before irreversible left ventricular damage occurs. Advanced cardiac imaging and CMR derived markers of diffuse myocardial fibrosis could be utilized for this purpose. FIB-AS study is intended to invasively and non-invasively assess diffuse myocardial fibrosis in AS patients and investigate its prognostic significance in post-interventional outcomes. The results of the study will expand the current knowledge of cardiac remodeling in AS and will bring additional data on myocardial fibrosis and its clinical implications following AVR.Ethics/disseminationThe study has full ethical approval and is actively recruiting patients. The results will be disseminated through scientific journals and conference presentations.Trial registrationClinicalTrials.govNCT03585933. Registered on 02 July 2018.

Transcatheter Aortic Valve Replacement in the Coronavirus Disease 2019 (COVID-19) Era.

Transcatheter Aortic Valve Replacement in the Coronavirus Disease 2019 (COVID-19) Era.

Sex-differences in aortic stenosis: Effect on functional capacity and prognosis

BackgroundThe patterns of left ventricular (LV) remodeling in aortic stenosis (AS) are different in men and women. We aimed to assess whether there were also sex differences in measurements obtained on exercise testing. MethodsEchocardiography and ETT (modified Bruce) were performed at presentation in 316 patients with moderate or severe AS. An early rapid rise in heart rate (RR-HR) during ETT was defined as achieving at least 85% of target heart rate or ≥50% increase from baseline within the first 6 min. ResultsMean age was 66 ± 12 years in men (n = 212) and 65 ± 12 years in women (n = 104) (p = NS). Men walked longer than women on the treadmill (10.4 ± 4.3 vs. 8.2 ± 4.2 min, p < 0.001) and achieved higher METs (9.2 ± 4.5 vs. 7.6 ± 4.3, p < 0.001), but both sexes achieved similar levels of peak heart rate and blood pressure. During a mean follow up of 34.9 ± 34.6 months, 29 deaths occurred (20 in men and 9 in women, p = 0.821). Age and body mass index were strong determinants of lower METs in men, but not in women, while Zva was a determinant in women but not in men. RR-HR was a strong determinant of lower METs in both sexes. Event-free survival was significantly lower in men with RR-HR but not in women. ConclusionExercise capacity was lower in women than men, and the determinants of exercise capacity differed. An RR-HR was a strong determinant of lower METs in both sexes, but predicted all-cause mortality only in men.

IMPAIRED MYOCARDIAL FLOW RESERVE AND LEFT VENTRICULAR REMODELING IN AORTIC STENOSIS

Coronary microvascular dysfunction (CMD) has been implicated in maladaptive left ventricular (LV) remodeling in aortic stenosis (AS). In a retrospective cohort of control patients and patients with aortic sclerosis or stenosis with normal perfusion on rest/stress 82Rubidium PET and LV ejection

Epicardial fat amount is associated with the magnitude of left ventricular remodeling in aortic stenosis.

Both genetic and environmental factors interact to control left ventricular (LV) remodeling in the context of aortic stenosis (AS). Epicardial adipose tissue (EAT) is a specific visceral adipose tissue with paracrine properties in close contact with the myocardium. We sought to assess determinants of EAT amount and its association with the magnitude and pattern of LV remodeling in patients suffering from severe AS. Between January 2014 and September 2017, we prospectively explored consecutive patients referred to our Heart Valve Center for SAVR presenting with severe AS and normal left ventricular ejection fraction (> 50%). Comprehensive transthoracic echocardiography (TTE) including assessment of LV remodeling and EAT amount were performed. 202 patients were included. EAT was significantly larger in elderly, diabetic and obese patients. EAT thickness was correlated positively with indexed LV mass in AS (r2 = 0.21; p < 0.0001) as well as severe LV remodeling pattern. Importantly, this observation persisted after adjustment for other factors associated with LV remodeling (β ± SE = 1.74 ± 0.34; p < 0.0001). Large amounts of EAT are positively and independently associated with more pronounced and severe LV remodeling in severe AS. Further exploration regarding the impact of functional properties of EAT on LV remodeling is required.

Sex Dimorphism in the Myocardial Response to Aortic Stenosis

ObjectivesThe goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers. BackgroundAS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping. MethodsThis study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro–brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. ResultsIn 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro–brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001). ConclusionsCMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471)

Impact of Valvuloarterial Impedance on Concentric Remodeling in Aortic Stenosis and Its Regression after Valve Replacement.

BackgroundLeft ventricle (LV) in patients with aortic stenosis (AS) faces a double hemodynamic load incorporating both valvular stenosis and reduced systemic arterial compliance (SAC). This study aimed to evaluate the impact of global LV afterload on LV hypertrophy (LVH) before and after aortic valve replacement (AVR).MethodsThe study cohort included 453 patients (247 males; mean age, 64 ± 11 years) who underwent AVR. Pre- and post-AVR echocardiographic examinations were retrospectively analyzed including an index of valvuloarterial impedance (ZVA) and LV mass index/LV end-diastolic volume index (LVMI/LVEDVI) as a parameter of LVH.ResultsPre-AVR LVMI/LVEDVI was 2.7 ± 0.9 g/mL with an aortic valve area (AVA) of 0.6 ± 0.2 cm2. ZVA was 5.9 ± 1.9 mm Hg/mL/m2 and showed a stronger correlation (β = 0.601, p < 0.001) with pre-AVR LVMI/LVEDVI than indexed AVA (β = 0.061, p = 0.19), transvalvular peak velocity (β = 0.211, p < 0.001). During a median follow-up of 3.5 years, patients had a 18.8 ± 10.4% decrease in the LV geometry index with a decrease in SAC from 1.20 ± 0.48 to 1.00 ± 0.38 mL/m2/mm Hg (p < 0.001). Pre-AVR LV ejection fraction (r = 0.284, p < 0.001) and ZVA (r = 0.523, p < 0.001) were independent factors associated with LVH regression in 322 patients with follow-up duration >1 year after AVR.ConclusionZVA is a major determinant of concentric remodeling in AS before AVR and LVH regression after AVR, which should be incorporated in routine evaluation of AS.

T1 mapping in severe aortic stenosis: insights into LV remodeling

Background Aortic stenosis (AS) appears to be not just a disease of the valve, with adaptive and maladaptive myocardial remodeling playing a key role. Left ventricular (LV) remodeling in AS is characterized by cellular hypertrophy and diffuse myocardial fibrosis. Macroscopic patterns differ between patients: as hypertrophy increases, the pattern changes from normal to concentric remodeling, concentric hypertrophy and finally decompensation. T1 mapping allows non-invasive estimation of diffuse myocardial fibrosis (native T1 and extracellular volume fraction; ECV). We use this methodology to investigate and correlate macroscopic and tissue level patterns of LV remodeling in AS patients prior to aortic valve replacement (AVR) as part of a larger outcome study (RELIEF-AS Study: NCT 02174471).