BACKGROUND:Diastolic dysfunction in the setting of aortic valve replacement (AVR) for aortic stenosis (AS) is incompletely understood. This study aims to assess the net hydraulic force of left ventricular (LV) filling in participants with severe symptomatic AS undergoing AVR. METHODS:This single-centre prospective observational cohort study evaluated patients with severe, symptomatic AS undergoing AVR between 2012 and 2015. Clinical assessment and cardiovascular magnetic resonance were completed prior to AVR and 1-year post-operatively. Atrioventricular area difference (AVAD) was used as a surrogate for the hydraulic force of LV filling. AVAD at mid-diastole was measured as the difference between LV short-axis area and left atrial short-axis area. RESULTS:In patients with AS (n = 110, 54% [59/110] male, age 71 [64-77] years, aortic valve area 0.74 ± 0.25 cm2), AVAD was positive at baseline (2.8 ± 6.5 cm2), consistent with a net hydraulic force assisting LV filling. While AVAD did not change post-operatively on a group level (p = 0.70), an improvement in AVAD was associated univariably with increasing baseline LV ejection fraction, and decreasing baseline AVAD, LV volume, mass, myocardial extracellular volume, and infarct size (p<0.05 for all), and multivariably with baseline decreasing AVAD, LV mass, and age (model adjusted R2 = 0.49, p<0.001). CONCLUSION:In severe AS, hydraulic force contributes to LV filling prior to and following AVR. The greatest improvement in hydraulic force following AVR occurred in those with the lowest baseline hydraulic force, but also with lower age and the absence of otherwise deleterious LV myocardial remodelling.

Importance:Patients undergoing aortic valve replacement (AVR) for chronic severe aortic regurgitation (AR) based on current guideline-based thresholds may have irreversible myocardial scarring. Objective:To quantify reverse remodeling, functional recovery, and symptomatic change after AVR and assess whether myocardial fibrosis is associated with incomplete recovery. Design, Setting, and Participants:In this prospective longitudinal observational study, patients with chronic severe AR referred for AVR by a cardiology team were included. Key exclusion criteria were previous valve surgery, moderate or greater valve disease, and other primary cardiomyopathies. Included patients underwent paired biomarkers, echocardiography, cardiopulmonary exercise testing, and cardiovascular magnetic resonance (CMR) at baseline and at a median of 7 months after AVR. The study took place at 2 tertiary cardiothoracic centers in London, United Kingdom, with enrollment from August 2021 to October 2023. Data were analyzed from January to April 2026. Exposure:AVR. Main Outcomes and Measures:Left ventricular (LV) reverse remodeling (change in LV end-diastolic volume [LVEDV] and LV mass) post-AVR and preoperative correlates of incomplete recovery, with prespecified focus on CMR fibrosis markers (late gadolinium enhancement [LGE] and extracellular volume [ECV]). Results:Seventy-two patients (median [IQR] age, 60 [6-70] years; 59 [82%] male, 35 [49%] with bicuspid aortic valve) completed paired studies. Median (IQR) regurgitant volume fell from 61 (38-83) mL to 5 (3-8) mL; median (IQR) LVEDV fell 44% from 273 (211-307) mL to 153 (130-177) mL; and median (IQR) LV mass fell 21% from 200 (159-226) g to 158 (137-184) g (all P < .001). Indexed intracellular volume declined 21% and indexed extracellular volume 15% (26 mL/m2 to 22 mL/m2; P < .001), raising extracellular volume fraction (ECV%) from 27.4% to 29.1% (P < .001). LGE as a percentage of LV mass was unchanged (2.3% to 2.4%; P = .36); baseline LGE burden was associated with less regression of LV mass (χ22 = 29.4; P < .001) and LVEDV at 7 months (χ21 = 7.9; P = .007). New York Heart Association class and quality of life improved (median [IQR] EQ-5D index improved from 0.89 [0.78-1.00] to 0.94 [0.81-1.00]; P < .001), but maximum oxygen consumption was unchanged (22.6 mL/kg/min to 21 mL/kg/min; P = .08). N-terminal pro-B-type natriuretic peptide decreased slightly (228 pg/mL to 198 pg/mL; P = .27), with a larger fall in patients with evidence of decompensation (n = 31; 469 pg/mL to 279 pg/mL; P = .02). Conclusions and Relevance:In this study, AVR was associated with substantial reverse remodeling at 7 months, including regression of hypertrophy and a fall in indexed extracellular (matrix) volume; the extracellular volume fraction rose, as cellular regression outpaced matrix regression. Focal scar, as a proportion of myocardium, was unchanged. Preoperative focal scar was independently associated with less recovery and may mark incomplete remodeling. Objective functional recovery did not improve at this time point.

BACKGROUND:Diffuse fibrosis is central to the pathophysiology of aortic stenosis (AS), can be assessed using cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV%), and is associated with mortality. The relevance of this signal to long-term prognosis remains unclear. We aim to assess predictors of long-term mortality with focus on diffuse fibrosis. METHODS:Single-center prospective observational cohort study of patients with severe, symptomatic AS undergoing aortic valve replacement (AVR). Patients were assessed using echocardiography, high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and CMR, including T1 mapping for ECV% quantification. All-cause mortality was identified using the NHS National Spine Database. Univariable and multivariable Cox regression models were fitted to assess all-cause mortality associations. RESULT:One hundred and sixty-eight patients (age 72 [65-77] years, 55% [92/168] male) underwent CMR. Over a follow-up period of 9.7 (6.8-10.9) years, 76 deaths occurred. Patients who died had higher ECV% (29.9% vs 27.6%, p = 0.014) and greater late gadolinium enhancement (3.9% vs 2.0%, p = 0.013). Univariable predictors of mortality were age, atrial fibrillation (AF), left atrial area, left atrial volume, total cholesterol, triglycerides, HDL:LDL ratio, non-bicuspid aortic valve, hs-cTnT, NT-proBNP, EuroSCORE II and ECV%. On multivariable regression, age, AF and ECV% remained significant predictors of mortality, independently of sex. AIC indicated that the model with four covariates was preferable to the one also including EuroSCORE II and coronary artery disease, and this result was confirmed by a likelihood ratio test (p=0.387). CONCLUSIONS:In the longest follow-up cohort of T1 mapping in severe AS, we demonstrate diffuse fibrosis remains an independent predictor of long-term mortality. Integration of ECV% in baseline risk stratification should be explored further in patients with AS undergoing AVR.

Aims:Computed tomography (CT) is increasingly being recognized as a diagnostic modality across a range of cardiovascular conditions. Myocardial late enhancement imaging has shown value as an imaging biomarker for the identification and prognostication of disease. The objective of this study was to compare extracellular volume fraction by CT (ECVCT) against cardiovascular magnetic resonance (ECVCMR), the latter considered as reference standard for this study. Methods and results:Consecutive patients with an index history of cardiac chest pain referred for invasive angiography were prospectively recruited. In addition to late gadolinium enhancement (LGE) imaging, patients underwent 1.5 T CMR with T1-mapping [by MOdified Look-Locker Inversion (MOLLI) recovery]. Pre- and post-contrast CT was performed for whole-heart ECVCT quantification. Averaged and segmental ECVCT was compared in patients with and without LGE, as well as between mid-ventricular averaged ECVCT and ECVCMR. Bland-Altman analysis was used to determine limits of agreement and identify differences between ECVCT and ECVCMR. A total of 88 participants (74% male, mean age 59.8 ± 9.1 years) underwent ECVCT and LGE; 49 of these also underwent mid-ventricular ECVCMR. For these, the CMR and CTECV fractions were 27.6 ± 2.4 and 26.8 ± 2.2, respectively. Patients with LGE findings on CMR (n = 24) had a significantly higher ECVCT than those without (n = 64): 27.2 [25.8, 28.7] vs. 26.1 [25.0, 27.7] (P = 0.02). Segments with LGE demonstrated a consistently higher ECV: 30.8 [25.7, 35.9] (P = 0.008) (endocardial LGE) and 30.9 [27.9, 33.1] (P = 0.0001) (transmural LGE) vs. 26.1 [25.0, 27.4]. Conclusion:ECVCT obtained from 5 min post-contrast CT protocols shows good agreement with CMR in a stable chest pain cohort. Such a protocol could be seamlessly introduced into a CT workflow for the identification of significant secondary pathologies.

In patients with aortic stenosis (AS), the relation of cardiac energetic pathways with cardiac structure and function, their changes, and their prognostic significance are not well understood. We aimed to characterize metabolic profiles in patients with severe AS before and after aortic valve replacement (AVR) and their association with functional status, structural remodeling and mortality. Patients with symptomatic, severe AS before (n = 143) and 1-year after (n = 113) AVR underwent cardiac magnetic resonance (CMR), serum cardiac biomarkers, and 6-minute walk test. Resting nonfasting plasma samples underwent targeted nuclear magnetic resonance (NMR) for fatty acids (FA), branched chain amino acids (BCAAs), glycolysis-related metabolites, and ketones. Lower FA and BCAA concentrations, but not glycolysis metabolites or ketones, correlated with greater myocardial mass and focal fibrosis, NT-proBNP, TnT and 6-minute walk distance. After 10.5 years of follow-up (66/143 deaths), lower FAs and BCAAs, but not ketones were independently associated with higher mortality risk (p <0.05). At 1-year after AVR, FAs had decreased compared to baseline. In conclusion, reduced serum FA and BCAA concentrations are cardiac, maladaptive, prognostic metabolic changes to AS, which are not reversible after AVR. Whether these markers may be used to guide the timing of AVR or provide metabolic risk stratification remains to be evaluated by future research. In patients with AS systemic metabolomics and their association with myocardial remodeling and outcome after AVR are largely unknown. We show that in severe AS low levels of unsaturated FA and BCAAs correlate with higher mortality risk, and biomarkers measured by CMR, serum, and functional incapacity, and do not increase after AVR. This may provide an alternate approach to risk stratification using blood biomarkers or guide targeted therapies to myocardial energetics before or after AVR.

Current guideline criteria for surgical intervention in chronic aortic regurgitation (AR) rely on fixed thresholds of left ventricular size and ejection fraction, but these metrics may overlook early myocardial injury and under-appreciate patient heterogeneity, particularly in women and older adults. Cardiovascular magnetic resonance (CMR) offers robust quantification of regurgitant volume, three-dimensional ventricular volumes, and both focal (late gadolinium enhancement) and diffuse (T1-mapping-derived extracellular volume) fibrosis. Observational studies have linked CMR-detected fibrosis to worse clinical outcomes and less favourable reverse remodelling after valve intervention, suggesting that fibrosis may mark the transition from compensated overload to irreversible myocardial damage. In this narrative review, we appraise the limitations of current guidelines, compare echocardiographic and CMR approaches to AR assessment, and summarize the evidence supporting myocardial fibrosis as a potential imaging biomarker for risk stratification. We discuss how integrating CMR-derived fibrosis metrics with volumetric and functional data could personalize timing of aortic valve intervention. While prospective studies are needed to validate fibrosis-guided decision-making, this evolving paradigm holds promise for earlier identification of patients at risk for irreversible myocardial injury, with the ultimate goal of preserving ventricular function and improving long-term outcomes.

Purpose: To investigate and mitigate the influence of physiological and acquisition-related parameters on myocardial blood flow (MBF) measurements obtained with myocardial Arterial Spin Labeling (myoASL). Methods: A Flow-sensitive Alternating Inversion Recovery (FAIR) myoASL sequence with bSSFP and spoiled GRE (spGRE) readout is investigated for MBF quantification. Bloch-equation simulations and phantom experiments were performed to evaluate how variations in acquisition flip angle (FA), acquisition matrix size (AMS), heart rate (HR) and blood T-1 relaxation time (T-1,T-B) affect quantification of myoASL-MBF. In vivo myoASL-images were acquired in nine healthy subjects. A corrected MBF quantification approach was proposed based on subject-specific T-1,T-B values and, for spGRE imaging, subtracting an additional saturation-prepared baseline from the original baseline signal. Results: Simulated and phantom experiments showed a strong dependence on AMS and FA (R-2>0.73), which was eliminated in simulations and alleviated in phantom experiments using the proposed saturation-baseline correction in spGRE. Only a very mild HR dependence (R-2>0.59) was observed which was reduced when calculating MBF with individual T-1,T-B For corrected spGRE, in vivo mean global spGRE-MBF ranged from 0.54 to 2.59 mL/g/min and was in agreement with previously reported values. Compared to uncorrected spGRE, the intra-subject variability within a measurement (0.60 mL/g/min), between measurements (0.45 mL/g/min), as well as the inter-subject variability (1.29 mL/g/min) were improved by up to 40% and were comparable with conventional bSSFP.

PurposeEvaluate the feasibility of quantification of Relaxation Along a Fictitious Field in the 2nd rotating frame (RAFF2) relaxation times in the human myocardium at 3 T.MethodsTRAFF2 mapping was performed using a breath-held ECG-gated acquisition of five images: one without preparation, three preceded by RAFF2 trains of varying duration, and one preceded by a saturation prepulse. Pixel-wise TRAFF2 maps were obtained after three-parameter exponential fitting. The repeatability of TRAFF2, T1, and T2 was assessed in phantom via the coefficient of variation (CV) across three repetitions. In seven healthy subjects, TRAFF2 was tested for precision, reproducibility, inter-subject variability, and image quality (IQ) on a Likert scale (1 = Nondiagnostic, 5 = Excellent). Additionally, TRAFF2 mapping was performed in three patients with suspected cardiovascular disease, comparing it to late gadolinium enhancement (LGE), native T1, T2, and ECV mapping.ResultsIn phantom, TRAFF2 showed good repeatability (CV < 1.5%) while showing no (R2=0.09) and high (R2=0.99) correlation with T1 and T2, respectively. Myocardial TRAFF2 maps exhibited overall acceptable image quality (IQ = 3.0±1.0) with moderate artifact levels, stemming from off-resonances near the coronary sinus. Average TRAFF2 time across subjects and repetitions was 79.1 ± 7.3 ms. Good precision (7.6 ± 1.4%), reproducibility (1.0 ± 0.6%), and low inter-subject variability (10.0 ± 1.8%) were obtained. In patients, visual agreement of the infarcted area was observed in the TRAFF2 map and LGE.ConclusionMyocardial TRAFF2 quantification at 3 T was successfully achieved in a single breath-hold with acceptable image quality, albeit with residual off-resonance artifacts. Nonetheless, preliminary clinical data indicate potential sensitivity of TRAFF2 mapping to myocardial infarction detection without the need for contrast agents, but off-resonance artifacts mitigation warrants further investigation.

Objectives Grading the severity of moderate mixed aortic stenosis and regurgitation (MAVD) is challenging and the disease poorly understood. Identifying markers of haemodynamic severity will improve risk stratification and potentially guide timely treatment. This study aims to identify prognostic haemodynamic markers in patients with moderate MAVD. Methods Moderate MAVD was defined as coexisting moderate aortic stenosis (aortic valve area (AVA) 1.0–1.5 cm 2 ) and moderate aortic regurgitation (vena contracta (VC) 0.3–0.6 cm). Consecutive patients diagnosed between 2015 and 2019 were included from a multicentre registry. The primary composite outcome of death or heart failure hospitalisation was evaluated among these patients. Demographics, comorbidities, echocardiography and treatment data were assessed for their prognostic significance. Results 207 patients with moderate MAVD were included, aged 78 (66–84) years, 56% male sex, AVA 1.2 (1.1–1.4) cm 2 and VC 0.4 (0.4–0.5) cm. Over a follow-up of 3.5 (2.5–4.7) years, the composite outcome was met in 89 patients (43%). Univariable associations with the primary outcome included older age, previous myocardial infarction, previous cerebrovascular event, atrial fibrillation, New York Heart Association >2, worse renal function, tricuspid regurgitation ≥2 and mitral regurgitation ≥2. Markers of biventricular systolic function, cardiac remodelling and transaortic valve haemodynamics demonstrated an inverse association with the primary composite outcome. In multivariable analysis, peak aortic jet velocity (Vmax) was independently and inversely associated with the composite outcome (HR: 0.63, 95% CI 0.43 to 0.93; p=0.021) in an adjusted model along with age (HR: 1.05, 95% CI 1.03 to 1.08; p<0.001), creatinine (HR: 1.002, 95% CI 1.001 to 1.003; p=0.005), previous cerebrovascular event (85% vs 42%; HR: 3.04, 95% CI 1.54 to 5.99; p=0.001) and left ventricular ejection fraction (LVEF) (HR: 0.97, 95% CI 0.95 to 0.99; p=0.007). Patients with Vmax ≤2.8 m/s and LVEF ≤50% (n=27) had the worst outcome compared with the rest of the population (72% vs 41%; HR: 3.87, 95% CI 2.20 to 6.80; p<0.001). Conclusions Patients with truly moderate MAVD have a high incidence of death and heart failure hospitalisation (43% at 3.5 (2.5–4.7) years). Within this group, a high-risk group characterised by disproportionately low aortic Vmax (≤2.8 m/s) and adverse remodelling (LVEF ≤50%) have the worst outcomes.