Low-flow Low-gradient Aortic Stenosis Research Articles

Diagnostic Challenges in Aortic Stenosis

Aortic stenosis (AS) is the most prevalent degenerative valvular disease in western countries. Transthoracic echocardiography (TTE) is considered, nowadays, to be the main imaging technique for the work-up of AS due to high availability, safety, low cost, and excellent capacity to evaluate aortic valve (AV) morphology and function. Despite the diagnosis of AS being considered straightforward for a very long time, based on high gradients and reduced aortic valve area (AVA), many patients with AS represent a real dilemma for cardiologist. On the one hand, the acoustic window may be inadequate and the TTE limited in some cases. On the other hand, a growing body of evidence shows that patients with low gradients (due to systolic dysfunction, concentric hypertrophy or coexistence of another valve disease such as mitral stenosis or regurgitation) may develop severe AS (low-flow low-gradient severe AS) with a similar or even worse prognosis. The use of complementary imaging techniques such as transesophageal echocardiography (TEE), multidetector computed tomography (MDTC), or cardiac magnetic resonance (CMR) plays a key role in such scenarios. The aim of this review is to summarize the diagnostic challenges associated with patients with AS and the advantages of a comprehensive multimodality cardiac imaging (MCI) approach to reach a precise grading of the disease, a crucial factor to warrant an adequate management of patients.

Right ventricular to pulmonary artery coupling in patients with different types of aortic stenosis undergoing TAVI.

Right ventricular (RV) dysfunction in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) has long been disregarded. We aimed to assess the predictive value of RV to pulmonary artery coupling (RV/PAc), defined as tricuspid annular plane systolic excursion to systolic pulmonary artery pressure, on mortality in different flow types of AS after TAVI. All patients undergoing TAVI for AS at our centre between 2018 and 2020 were assessed; 862 patients were analysed. The cohort was dichotomized using a ROC analysis (cut-off 0.512mm/mmHg), into 429 patients with preserved and 433 patients with reduced RV/PAc. Reduced RV/PAc was associated with male sex and a higher rate of comorbidities. Short-term VARC-3 endpoints and NYHA classes at follow-up were comparable. Reduced RV/PAc was associated with higher 2-year all-cause mortality (35.0% [30.3-39.3%] vs. 15.4% [11.9-18.7%], hazard ratio 2.5 [1.9-3.4], p < 0.001). Cardiovascular mortality was almost tripled. Results were consistent after statistical adjustment and in a multivariate model. Sub-analyses of AS flow types revealed lower RV/PAc in classical and paradoxical low-flow low-gradient AS, with the majority having reduced RV/PAc (74% and 59%). RV/PAc retained its predictive value in these subgroups. RV dysfunction defined by low RV/PAc is a strong mortality predictor after TAVI independent of flow group. It should be incorporated in future TAVI risk assessment.

Normal-Flow Low-Gradient AorticStenosis: Comparing the U.S. and European Guidelines.

Patients with normal-flow low-gradient (NFLG) severe aortic stenosis present both diagnostic and management challenges, with debate about the whether this represents true severe stenosis and the need for valve replacement. Studies exploring the natural history without intervention have shown similar outcomes of patients with NFLG severe aortic stenosis to those with moderate aortic stenosis and better outcomes after valve replacement than those with low-flow low-gradient severe aortic stenosis. Most studies (all observational) have shown that aortic valve replacement was associated with a survival benefit vs surveillance. Based on available data, the European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines and European Association of Cardiovascular Imaging/American Society of Echocardiography suggest that these patients are more likely to have moderate aortic stenosis. This clinical entity is not mentioned in the American Heart Association/American College of Cardiology guidelines. Here we review the definition of NFLG severe aortic stenosis, potential diagnostic algorithms and points of error, the data supporting different management strategies, and the differing guidelines and outline the unanswered questions in the diagnosis and management of these challenging patients.

A Complex Case with a Completely Percutaneous Solution: Treatment of a Severe Calcific Left Main in a Patient with Low-Flow Low-Gradient Aortic Stenosis

Background: This case study explores an integrated approach to managing a complex cardiac condition, presenting a comprehensive single-session intervention. This includes balloon valvuloplasty using a Nucleus 18 mm balloon, complex angioplasty with rotational atherectomy (rotablator) targeting calcified lesions in the left main and left anterior descending artery, and Transcatheter Aortic Valve Implantation (TAVI) with a 23 mm Sapien 3 valve, all performed on an 81-year-old woman. Furthermore, this report underscores the strategic left atrial appendage closure conducted three months post-procedure due to the patient’s elevated hemorrhagic risk. Case presentation: Facing critical coronary and valvular pathologies, the patient underwent a meticulously planned, single-session intervention. The process began with a balloon valvuloplasty using a Nucleus 18 mm balloon to address the aortic stenosis. This was followed by a high-risk angioplasty, during which the Impella CP device provided hemodynamic support and rotational atherectomy was employed to address the calcified coronary artery disease effectively. The same session saw the successful execution of TAVI using a 23 mm Sapien 3 valve. The comprehensive approach notably diminished procedural complications, illustrating the benefits of an integrated treatment pathway in managing high-risk patients. Three months later, the patient underwent a left atrial appendage closure, a critical move considering her high risk of hemorrhage. This procedure also provided an opportunity to assess the favorable outcomes of the previous angioplasty. Conclusion: This case validates the feasibility and efficacy of performing multiple advanced percutaneous interventions in a single session for high-risk cardiac patients. It underscores the crucial role of innovative and personalized treatment strategies in improving patient outcomes, particularly in complex clinical scenarios. Moreover, the case exemplifies the essential relationship between immediate, comprehensive intervention and subsequent follow-up procedures in ensuring optimal long-term patient care.

Long-Term Outcomes of Aortic Stenosis Patients with Different Flow/Gradient Patterns Undergoing Transcatheter Aortic Valve Implantation.

Background: Few data exist on the comparative long-term outcomes of severe aortic stenosis (AS) patients with different flow-gradient patterns undergoing transcatheter aortic valve implantation (TAVI). This study sought to evaluate the impact of the pre-TAVI flow-gradient pattern on long-term clinical outcomes after TAVI and assess changes in the left ventricular ejection fraction (LVEF) of different subtypes of AS patients following TAVI. Methods: Consecutive patients with severe AS undergoing TAVI in our institution were screened and prospectively enrolled. Patients were divided into four subgroups according to pre-TAVI flow/gradient pattern: (i) low flow-low gradient (LF-LG): stroke volume indexed (SVi) ≤ 35 mL/m2 and mean gradient (MG) < 40 mmHg); (ii) normal flow-low gradient (NF-LG): SVi > 35 mL/m2 and MG < 40 mmHg; (iii) low flow-high gradient (LF-HG): Svi 35 mL/m2 and MG ≥ 40 mmHg and (iv) normal flow-high gradient (NF-HG): SVi > 35 mL/m2 and MG ≥ 40 mmHg. Transthoracic echocardiography was repeated at 1-year follow-up. Clinical follow-up was obtained at 12 months, and yearly thereafter until 5-year follow-up was complete for all patients. Results: A total of 272 patients with complete echocardiographic and clinical follow-up were included in our analysis. Their mean age was 80 ± 7 years and the majority of patients (N = 138, 50.8%) were women. 62 patients (22.8% of the study population) were distributed in the LF-LG group, 98 patients (36%) were LF-HG patients, 95 patients (34.9%) were NF-HG, and 17 patients (6.3%) were NF-LG. There was a greater prevalence of comorbidities among LF-LG AS patients. One-year all-cause mortality differed significantly between the four subgroups of AS patients (log-rank p: 0.022) and was more prevalent among LF-LG patients (25.8%) compared to LF-HG (11.3%), NF-HG (6.3%) and NF-LG patients (18.8%). At 5-year follow-up, global mortality remained persistently higher among LF-LG patients (64.5%) compared to LF-HG (47.9%), NF-HG (42.9%), and NF-LG patients (58.8%) (log-rank p: 0.029). At multivariable Cox hazard regression analysis, baseline SVi (HR: 0.951, 95% C.I.; 0.918-0.984), the presence of at least moderate tricuspid regurgitation at baseline (HR: 3.091, 95% C.I: 1.645-5.809) and at least moderate paravalvular leak (PVL) post-TAVI (HR: 1.456, 95% C.I.: 1.106-1.792) were significant independent predictors of late global mortality. LF-LG patients and LF-HG patients exhibited a significant increase in LVEF at 1-year follow-up. A lower LVEF (p < 0.001) and a lower Svi (p < 0.001) at baseline were associated with LVEF improvement at 1-year. Conclusions: Patients with LF-LG AS have acceptable 1-year outcomes with significant improvement in LVEF at 1-year follow-up, but exhibit exceedingly high 5-year mortality following TAVI. The presence of low transvalvular flow and at least moderate tricuspid regurgitation at baseline and significant paravalvular leak post-TAVI were associated with poorer long-term outcomes in the entire cohort of AS patients. The presence of a low LVEF or a low SVi predicts LVEF improvement at 1-year.

Myocardial sodium-glucose cotransporter 2 expression and cardiac remodelling in patients with severe aortic stenosis: The BIO-AS study.

Cardiac remodelling plays a major role in the prognosis of patients with aortic stenosis (AS) and could impact the benefits of aortic valve replacement. Our study aimed to evaluate the expression of sodium-glucose cotransporter 2 (SGLT2) gene and protein in patients with severe AS stratified in high gradient (HG) and low flow-low gradient (LF-LG) AS and its association with cardiac functional impairments. Gene expression and protein levels of main biomarkers of cardiac fibrosis (galectin-3, sST2, serpin-4, procollagen type I amino-terminal peptide, procollagen type I carboxy-terminal propeptide, collagen, transforming growth factor [TGF]-β), inflammation (growth differentiation factor-15, interleukin-6, nuclear factor-κB [NF-κB]), oxidative stress (superoxide dismutase 1 [SOD1] and 2 [SOD2]), and cardiac metabolism (sodium-hydrogen exchanger, peroxisome proliferator-activated receptor [PPAR]-α, PPAR-γ, glucose transporter 1 [GLUT1] and 4 [GLUT4]) were evaluated in blood samples and heart biopsies of 45 patients with AS. Our study showed SGLT2 gene and protein hyper-expression in patients with LF-LG AS, compared to controls and HG AS (p < 0.05). These differences remained significant even after adjusting for age, gender, body mass index, history of diabetes mellitus, arterial hypertension, and coronary artery disease. SGLT2 gene expression was positively correlated with: (i) TGF-β (r = 0.72, p < 0.001) and collagen (r = 0.73, p < 0.001) as markers of fibrosis; (ii) NF-κB (r = 0.36, p < 0.01) and myocardial interleukin-6 (r = 0.68, p < 0.001) as markers of inflammation: (iii) SOD2 (r = -0.38, p < 0.006) as a marker of oxidative stress; (iv) GLUT4 (r = 0.33, p < 0.02) and PPAR-α (r = 0.36, p < 0.01) as markers of cardiac metabolism. In patients with LF-LG AS, SGLT2 gene and protein were hyper-expressed in cardiomyocytes and associated with myocardial fibrosis, inflammation, and oxidative stress.

Transcatheter aortic valve implantation impact on left ventricular myocardial damage: long term follow-up.

Aortic stenosis (AS) is causing myocardial damages and replacement is mainly indicated based on symptoms. Non-invasive estimation of myocardial work (MW) provide a less afterload dependent tool that, we sought to look at the impact of transcatheter aortic valve implantation (TAVI) on the myocardium at long-term follow-up and according to current indications. We conducted an observational, cross-sectional, single-center study. Patients were selected based on the validated indication for a TAVI. Standardized echocardiographies were repeated. 102 patients were included. Mean age was 85-year-old, 45% were female, 68% get high-blood pressure and 52% had a coronary disease. One fifth was suffering from low-flow low-gradient aortic stenosis. Follow-up was performed at 22 ± 9.5 months after the TAVI. No TAVI-dysfunction was observed. LVEF was stable (62 ± 8%), and global longitudinal strain get improved (-14.0% ± 3.7 vs -16.0% ± 3.6, p-value <0.0001). No improvement of the MW-parameters was noticed (Global Work Index (LV GWI) 2099 ± 692mmHg% vs 2066 ± 706mmHg%, p=0.8, Global Constructive (LV GCW) 2463 ± 736mmHg% vs 2463 ± 676mmHg%, p=0.8). Global Wasted Work increased (214 [149; 357] mmHg% vs 247 [177; 394] mmHg%, p= 0.0008). In a population of severe symptomatic AS-patients who had undergone a TAVI, the non-invasive myocardial indices that assess the LV performance at long term follow-up did not improve. These results are questioning the timing of the intervention and the need for a more attention in the pharmacological management of these AS-patients.

Paradoxical low flow-low gradient aortic stenosis: lights and shadows

Paradoxical low flow-low gradient aortic valve stenosis (AVS) is an increasing phenotype in the general population, particularly after the seventh decade of life. It is an AVS in which, despite the preserved ejection fraction, the mean transvalvular gradient is not suggestive of severe AVS (<40 mmHg). The pathophysiology is often intertwined with conditions resulting in heart failure with preserved ejection fraction, such as arterial hypertension and cardiac amyloidosis. Its management is rather controversial about the diagnosis and therapeutic management. The aims of this focus are: to clarify the role and reliability of the main available diagnostic methods, the efficacy of surgical and percutaneous treatments, and to develop a diagnostic-therapeutic algorithm for managing this condition in clinical practice. This algorithm will involve a multi-parametric evaluation, integrating standard echocardiographic assessment with three-dimensional planimetric valve area calculation, determination of the energy loss index), and calcium score calculation by computed tomography scan. This approach aims to ascertain the severity of the stenosis and determine the appropriate therapeutic management.

Carotid Duplex Ultrasonography to Assess Severity of Low-Flow Low-Gradient Aortic Stenosis

BackgroundPatients with low-flow, low-gradient aortic valve stenosis constitute a substantial subset of all severe aortic stenosis patients. However, assessment of true severity of these patients can be challenging. In this analysis, we study the utility of the common carotid artery waveforms to distinguish true from pseudo-severe low-flow low-gradient aortic stenosis. MethodsThis is an observational analysis that included patients who underwent a transthoracic echocardiogram (TTE) and duplex carotid ultrasonography (DCUS) and had low-flow, low-gradient aortic stenosis with reduced left ventricular ejection fraction (LVEF) on the index TTE (LVEF <50%, calculated aortic valve area [AVA] of ≤1.0 cm2, mean and peak gradient of <40 and <64 mm Hg, respectively, and stroke volume index <35 mL/m2). Patients were classified as pseudo-severe and true-severe aortic stenosis based on additional subsequent testing. Differences in various TTE and DCUS waveform parameters across the aortic valve and the common carotid artery were compared between the 2 groups. ResultsThe study included 30 patients (60 carotid arteries). Fifteen patients were categorized as pseudo-severe and 15 as true severe aortic stenosis. There were no significant differences in calculated AVA, LVEF, stroke volume/stroke volume index, and Doppler Velocity Index in the 2 groups. Mean and peak gradient were higher in patients with true-severe aortic stenosis. Carotid acceleration time (cAT) was significantly prolonged in patients with true-severe compared with pseudo-severe aortic stenosis. A cAT ≥80 ms was 83.3% sensitive and 83.3% specific for true-severe aortic stenosis. ConclusioncAT acceleration time may be used to distinguish true from pseudo-severe low-flow, low-gradient aortic valve stenosis.

Prognostic impact of cardiac damage staging classification in each aortic stenosis subtype undergoing TAVI.

The prognostic value of cardiac damage staging classifications across the haemodynamic spectrum of severe aortic stenosis (AS) remains unknown. We aimed to investigate the prognostic impact of cardiac damage staging classifications in patients with high-gradient AS (HG-AS) and low-gradient AS (LG-AS) undergoing transcatheter aortic valve implantation (TAVI). In a prospective TAVI registry, five-year mortality was evaluated for early stages of cardiac damage (stage 0, 1, or 2) and advanced stages of cardiac damage (stage 3 or 4) in patients with HG-AS, classical low-flow (LF) LG-AS, LF LG-AS with preserved ejection fraction (pEF), and normal-flow (NF) LG-AS. Among 2,090 patients undergoing TAVI, 1,045 patients had HG-AS, 337 patients had classical LF LG-AS, 394 patients had LF LG-AS with pEF, and 314 patients had NF LG-AS. The majority of patients with classical LF LG-AS exhibited advanced cardiac damage (73.6%), followed by LF LG-AS with pEF (55.6%), NF LG-AS (51.6%), and HG-AS (50.6%). Patients with advanced stage cardiac damage had significantly higher mortality after TAVI than those with early stage cardiac damage in all subtypes of AS (adjusted hazard ratio [HRadjusted] 1.66, 95% confidence interval [CI]: 1.34-2.06 for HG-AS; HRadjusted 1.49, 95% CI: 1.02-2.16 for classical LF LG-AS; HRadjusted 1.69, 95% CI: 1.22-2.35 for LF LG-AS with pEF; and HRadjusted 1.52, 95% CI: 1.04-2.32 for NF LG-AS). Cardiac damage staging classifications stratified mortality after TAVI irrespective of AS subtype.

Impact of cardiac staging classification in transcatheter aortic valve implantation for major subtypes of severe aortic stenosis

Abstract Background Staging classification to quantify the extent of extra-aortic valve cardiac damage is recognized as a useful prognostic tool in patients undergoing transcatheter aortic implantation (TAVI) for aortic stenosis (AS). However, this classification has not been validated in each AS subtype. Objectives The present study aimed to investigate the prognostic impact of staging classification in patients with four major AS subtypes. Methods In a prospective TAVI registry, patients were classified into high gradient AS (HG-AS), classical low flow low gradient AS (LFLG-AS), paradoxical LFLG-AS, and normal flow low gradient AS (NFLG-AS). Five-year mortality was compared between early stage (stage 0, 1, or 2) and advanced stage (stage 3 or 4). Results Among 1,507 patients undergoing TAVI, 812 patients had HG-AS, 186 patients had classical LFLG-AS, 277 patients had paradoxical LFLG-AS, and 232 patients had NFLG-AS. There were much difference in the distribution of cardiac stage among AS subtypes; advanced stage accounting for 54.3% in HG-AS, 58.6% in NFLG-AS, 62.5% in paradoxical LFLG-AS, and 80.6% in classical LFLG-AS. Patients with advanced stage had higher all-cause mortality compared with early stage in HG-AS and paradoxical LFLG-AS (HRadjusted 2.00; 95% CI 1.44-2.78 and HRadjusted 2.15; 95% CI 1.43-3.21), but not in classical LFLG-AS and NFLG-AS (HRadjusted 1.17; 95% CI 0.70-1.95 and HRadjusted 1.43; 95% CI 0.90-2.27). Conclusions Early stage was associated with a reduced risk for five-year mortality in patients with HG-AS and paradoxical LFLG-AS, while there was comparable mortality between early and advanced stages in patients with classical LFLG-AS and NFLG-AS.

Impact of route of access and stenosis subtype on outcome after transcatheter aortic valve replacement.

Previous analyses have reported the outcomes of transcatheter aortic valve replacement (TAVR) for patients with low-flow, low-gradient (LFLG) aortic stenosis (AS), without stratifying according to the route of access. Differences in mortality rates among access routes have been established for high-gradient (HG) patients and hypothesized to be even more pronounced in LFLG AS patients. This study aims to compare the outcomes of patients with LFLG or HG AS following transfemoral (TF) or transapical (TA) TAVR. A total of 910 patients, who underwent either TF or TA TAVR with a median follow-up of 2.22 (IQR: 1.22-4.03) years, were included in this multicenter cohort study. In total, 146 patients (16.04%) suffered from LFLG AS. The patients with HG and LFLG AS were stratified according to the route of access and compared statistically. The operative mortality rates of patients with HG and LFLG were found to be comparable following TF access. The operative mortality rate was significantly increased for patients who underwent TA access [odds ratio (OR): 2.91 (1.54-5.48), p = 0.001] and patients with LFLG AS [OR: 2.27 (1.13-4.56), p = 0.02], which could be corroborated in a propensity score-matched subanalysis. The observed increase in the risk of operative mortality demonstrated an additive effect [OR for TA LFLG: 5.45 (2.35-12.62), p < 0.001]. LFLG patients who underwent TA access had significantly higher operative mortality rates (17.78%) compared with TF LFLG (3.96%, p = 0.016) and TA HG patients (6.36%, p = 0.024). HG patients experienced a twofold increase in operative mortality rates following TA compared with TF access, while LFLG patients had a fivefold increase in operative mortality rates. TA TAVR appears suboptimal for patients with LFLG AS. Prospective studies should be conducted to evaluate alternative options in cases where TF is not possible.

Dobutamine stress echocardiography remains indispensable for the diagnosis of low-flow low-gradient severe aortic stenosis

Abstract Background In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, current guidelines recommend dobutamine stress echocardiography (DSE) to determine valve stenosis severity. Additionally, aortic valve calcification (AVC) scores are also used with this intent. Previous studies have determined cut-off values of ≥2000AU for men and ≥1200AU for women to distinguish between true severe AS and pseudosevere AS. Purpose To assess the relationship between AVC and DSE in low-flow low-gradient aortic stenosis. Methods We performed a multicenter international registry study including patients that underwent DSE to determine AS severity and multi-slice computed tomography (MSCT) of sufficient quality to determine AVC scores. Severe AS was diagnosed when resting peak aortic valve velocity was ≥4.0 m/s, or stress aortic valve area (AVA) remained &amp;lt;1.0cm2 at peak dobutamine stress levels; moderate AS was diagnosed when resting AVA was ≥1.0cm2 and peak velocity was &amp;lt; 4.0m/s or stress AVA exceeded 1.0cm² at peak stress. Using the previous cut-off values, MSCT-AVC scores were compared to DSE-derived AS diagnoses to determine sensitivity and specificity of AVC, and the positive and negative predictive values of high and low scores. Subsequently, we performed a receiver-operating characteristics (ROC)-curve analysis for men and women separately. Results We included 271 patients from 8 centers, of which 231 patients had sufficiently interpretable DSE and MSCT. Median age was 79 years (Interquartile range (IQR): 71-84), median BMI was 26.4 kg/m2 (IQR: 24.1-30.0) and median BSA was 1.9 m2(IQR: 1.8-2.1). Left ventricular ejection fraction was reduced (&amp;lt;50%) in 209 (90.5%) patients. Bicuspid valve morphology was present in 20 patients (8.7%). DSE confirmed severe AS in 103 patients, 4 of whom already had resting peak aortic valve velocity ≥4.0m/s. Moderate AS was diagnosed in 128 patients, of which 76 had a resting AVA ≥ 1.0cm2. Characteristics of these patients are summarized the table. Of the patients with severe AS, 49 (47.6%) had a high AVC score (≥2000 for men or ≥1200 for women) and of patients with moderate AS, 75 (58.6%) had an AVC score below those cut-off values. This corresponds to a sensitivity of 47.6%, a specificity of 58.4% and positive and negative predictive values of 53.5% and 51.6%, respectively. The ROC-curves are shown in the figure; the area under the curve was 0.55 for men and 0.52 for women, signifying poor discriminative performance. Conclusion In this multicenter international registry we found that aortic valve calcification scores correlated poorly with AS severity and therefore DSE remains the preferred technique to assess borderline AS severity.Table.Patient characteristicsFigure.ROC curve

The potential role of the aortic valve calcium score by computed tomography scan in the diagnosis of concomitant cardiac amyloidosis in patients with severe aortic stenosis

Abstract Background Cardiac amyloidosis (CA) and aortic stenosis (AS) are two related, but the diagnosis of both these condition is challenging because of the common phenotype. Different predictors of CA in AS have been proposed in the last years. Purpose To identify a new red-flag of concomitant CA in patients with severe AS analyzing aortic valve calcium burden using calcium score, calcium mass and calcium volume by computed tomography scan (CT). Methods 55 patients with severe AS and suspicion of concomitant CA were retrospectively enrolled from 2009 to 2022. 5 Patients with a bicuspid aortic valve, previous aortic valve replacement, or an incomplete diagnostic workup for CA were excluded. 50 patients underwent CT-scan and were included in the final analysis. Results Of the 50 patients, 21 patients (AS-CA) had positive 99m Tc-DPD bone scintigraphy (19 with score 2 and 2 with score 3), none of the patients presented laboratory suspicion for AL amyloidosis, so all the patients had a diagnosis of transthyetin related CA. 29 patients (AS alone) had negative bone scintigraphy. AVA indexed were comparable between AS-CA and AS alone groups (0.3 mm2/m2, in both the group p: 0.88). Stroke volume, maximum and mean gradient were significatively lower in AS-CA group (29 vs 36 ml/m2, p: 0.01, 60 vs 72 mmHg, p: 0.016 and 34 vs 45 mmHg, p:0.01) with a higher percentage of low flow-low gradient aortic stenosis in AS-CA group (11 patients,52% vs 5 patients in AS-alone 17%, p: 0.014)ECG in AS-CA group showed atrial fibrillation in 12 patients (57%), versus 3 patients in the AS-alone group (10%), and lower QRS voltages (peripheral QRS score 44 mV vs 58 mV, p-value:0.017; total QRS score 120 mV versus 160 mV, p-value: 0.005). The echocardiogram showed a more thickened IVS and PW in AS-CA patients (17 versus 15 mm, p: 0.03 and 15 versus 14 mm, p: 0.01) with a decreases longitudinal systolic function (septal S wave at TDI 4.4 vs 5.1 cm/s, p: 0.011, lateral S wave 4.5 versus 5.6 cm/s, p: 0.014).CT- aortic valve calcium was quantified by an experienced operator. A statistically significant difference between AS-CA and AS-alone groups was observed in calcium score (3569 vs 4480 Agatston units, p: 0.017) calcium volume (2575 vs 3445 mm3, p: 0.012) and calcium mass (798 vs 1082 g, p: 0.016).At logistic regression analyses,confirmed perdictors of concomitant CA in AS were: AS low flow- low gradient (p:0.011), atrial fibrillation (p:0.001), lower QRS score periferical(p:0.004) and total (p:0.002) and a decreased longitudinal systolic function (p:0.028). Regarding the aortic valve calcium burden, calcium score( p:0.031) and calcium volume(p:0.026) were confirmed predictor of CA in AS. Conclusions This study shows that calcium burden at CT scan in patients with concomitant CA-AS is significatily lower than in patients with AS alone. Calcium burden at CT scan could be used in addition to the classical parameters as a potential red-flag of concomitant CA in AS severe.

Right-ventricular/pulmonary artery coupling predicts long-term mortality in aortic stenosis patients with different flow types

Abstract Background Right-ventricular (RV) dysfunction in aortic stenosis (AS) patients undergoing transcatheter aortic valve implantation (TAVI) has long been neglected. Right-ventricular to pulmonary artery coupling (RV/PAc), a parameter of RV function, can be determined by echocardiography (tricuspid annular plane systolic excursion over systolic pulmonary artery pressure). Its use for mortality prediction in contemporary AS patients warrants further evaluation, data for different flow types of AS are lacking. Purpose To assess the impact of pathological RV/PAc on long-term mortality in AS patients with different flow types. Methods All 1577 consecutive patients from our registry from 2018 to 2020 were assessed. Patients without tricuspid regurgitation (n=523) or inconclusive echocardiography images (n=111) were excluded. RV/PAc could be analysed in 862 patients. To dichotomize the cohort, a receiver operator curve (ROC) analysis for 2-year mortality was used. Primary endpoint was 2-year mortality. Patients were further analysed according to the Valve Academic Research Consortium (VARC) 3 endpoint definitions. Results By ROC analysis, 0.512 mm/mmHg was defined as a cut-off, dividing the cohort into 428 patients with physiological RV/PAc (above cut-off) and 434 patients with pathological RV/PAc. Patients with pathological RV/PAc were more often male, had more comorbidities, a lower ejection fraction (50% [40-55%] vs. 55% [53-58%], p&amp;lt;0.01) and a higher Society of Thoracic Surgeons (STS) score (4.0 [2.5-6.0] vs. 2.8 [2.0-4.0], p&amp;lt;0.01). Procedural outcomes according to VARC-3 were comparable: the composite endpoints technical failure and device failure at 30 days occurred in 3.9% and 3.5% (p=0.75) and 11.3% and 13.3% (p=0.42) in the pathological and physiological group, respectively. Clinical outcomes in terms of New York Heart Association functional class were comparable at follow-up, with an improvement by at least one class in 76.2% (pathological group) and 79.9% (physiological group, p=0.33). All-cause 2-year mortality was significantly higher in the pathological group (34.9% [30.2-39.2%] vs. 15.4% [11.9-18.8%], p&amp;lt;0.01, hazard ratio, HR, 2.5 [1.9-3.4], Figure 1). The result persisted when adjusted for STS score (HR 2.3 [1.7-3.1]) or in a multivariate Cox regression. Cardiovascular mortality was increased too (pathological, 23.7% [19.3-27.8%], vs. physiological, 8.5% [5.8-11.2%], HR 2.9 [2.0-4.2], p&amp;lt;0.01). The fraction of patients with pathological RV/PAc differed significantly across the AS flow types (high-gradient, 40.3%, classical low-flow low-gradient (LFLG), 73.9%, paradoxical LFLG, 58.9%, and normal-flow low-gradient, 36.6%, p&amp;lt;0.01). Mortality differences persisted in high-gradient and LFLG groups (Figure 2A-D), which was consistent after statistical adjustment. Conclusions RV dysfunction defined as low RV/PAc is a strong predictor for long-term mortality in TAVI patients, with a strong prognostic value also in LFLG AS.

Prognostic impact of atrial fibrillation in patients with paradoxical low-flow low-gradient aortic stenosis undergoing TAVI

Abstract Background Atrial fibrillation (AF) has been associated with adverse clinical outcomes after transcatheter aortic valve implantation (TAVI). However, the impact of AF on post-TAVI flow status and clinical outcomes in patients with paradoxical low-flow low-gradient aortic stenosis (PLFLG-AS) is still unclear. Objectives The present study aimed to investigate the effect of AF on post-TAVI flow status and clinical outcomes in patients with PLFLG-AS undergoing TAVI. Methods In a prospective TAVI registry, patients with preserved left ventricular ejection fraction (LVEF ≥50%) were stratified according to the flow-gradient status and presence of AF. Results Among 2,259 TAVI patients with preserved LVEF between August 2007 and June 2021, 765 had high-gradient AS (HG-AS) (mean gradient ≥40 mmHg) and 444 had PLFLG-AS (mean gradient &amp;lt;40 mmHg and stroke volume index [SVi] &amp;lt;35 ml/m2). AF was observed in 199 patients with HG-AS (26.0%) and 190 patients with PLFLG-AS (42.8%). At 1 year after TAVI, SVi was significantly improved in PLFLG-AS patients with no AF, whereas those with AF remained low-flow status (from 25.9 ± 8.5 mL/m2 to 37.2 ± 9.9 mL/m2 and from 26.8 ± 5.1 mL/m2 to 26.1 ± 9.1 mL/m2, respectively). PLFLG-AS patients had an increased risk of all-cause mortality at 1 year after TAVI compared with those without AF (HRadjust 2.79; 95% CI 1.58-4.93). Whereas PLFLG-AS patients with no AF had a similar mortality compared with HG-AS patients with no AF (HRadjust 0.84; 95% CI 0.49-1.44). Conclusions AF was associated with worse flow status and impaired prognosis after TAVI in patients with PLFLG-AS.

Abstract 18349: The Impact of Concomitant Mitral Regurgitation on Aortic Valve Intervention Outcomes in Paradoxical Low-Flow Low-Gradient Severe Aortic Stenosis

Background: Patients with paradoxical low flow low gradient severe aortic stenosis (LFLGAS) exhibit low transvalvular flow rates due to reduced stroke volumes, while maintaining preserved left ventricular ejection fraction (LVEF). The presence of mitral regurgitation (MR) adds complexity to this already challenging diagnosis, by further lowering flow rate. However, the impact of aortic valve intervention in this patient population remains uncertain. Methods: A total of 1178 patients were included from an institutional echo database with adjudicated aortic valve area (AVA &lt;1.0 cm2), transaortic gradients (mean gradient&lt; 40 mmHg) and low flow rate (Q ≤210 ml/sec), to confirm the diagnosis of LFLGAS and preserved LVEF (&gt;50%). Subgroups were formed based on the presence of severe MR and subsequent surgical and transcatheter aortic valve intervention (SAVR/TAVR). Patients who underwent mitral valve intervention were censored. All-cause mortality was assessed as the primary outcome. Results: Patients with severe MR had significantly lower flow rates compared to patients w/o severe MR (166.5 ± 26.3 vs 174.7 ± 25, p=0.006). During a median follow up of 1.3 years, 745 deaths (62.2%) were identified, with a cumulative incidence significantly lower in the intervention groups (Figure). After multivariate propensity adjustment for age, sex, aortic valve area and comorbidities, aortic valve intervention showed a significant reduction in mortality risk in both intervention groups, which was more pronounced in the severe MR group compared to patients w/o severe MR (AdjHR 0.334, p=0.015 vs 0.436, p&lt;0.001, p for interaction =0.24). Conclusions: In paradoxical low-flow low-gradient severe aortic stenosis, aortic valve intervention results in a survival benefit, especially among patients with concomitant severe MR. Our findings highlight the importance of recognizing severe MR as a flow-diverting lesion that can impact outcomes in LFLGAS.

Short-Term Outcomes Following Transcatheter Aortic Valve Implantation: Classical Low-Flow Low-Gradient Versus Normal-Flow Low-Gradient Severe Aortic Stenosis

Background: Both classical severe low-flow low-gradient aortic stenosis (LFLG-AS) and severe normal-flow low-gradient aortic stenosis (NFLG-AS) patients undergo transcatheter aortic valve implantation (TAVI). However, few studies have compared outcomes between the two groups. Our study aimed to assess short term post-TAVI outcomes between classical LFLG-AS and NFLG-AS. Methods: We conducted a retrospective, single-center, analysis of 206 patients who underwent TAVI between January 2011 to September 2020. Of these, 44 (males: 33) had classical LFLG-AS and 162 (males: 89) had NFLG-AS. Six-month primary outcomes included all-cause and cardiovascular mortality. Multiple secondary outcomes were assessed including stroke, myocardial infarction (MI), new-onset atrial fibrillation, acute kidney injury (AKI), major bleeding, vascular complications, and repeat hospitalizations from cardiac causes. Results: The cumulative six-month all-cause and cardiovascular mortality were similar between classical severe LFLG-AS and NFLG-AS patients (6.81 % vs. 4.32 %, P = 0.49 and 2.27 % vs. 2.47 %, P = 0.93 respectively). All secondary outcomes were also similar, except for a statistically significant higher rate of AKI in patients with classical LFLG-AS (P = &lt; 0.0001). Conclusion: Except for a higher incidence of AKI in patients with severe classical LFLG-AS, six-month post-TAVI outcomes did not differ between classical LFLG-AS and NFLG-AS.

Outcomes of Transcatheter Aortic Valve Replacement Patients With Different Transvalvular Flow-Gradient Patterns

Low-flow low-gradient (LF-LG) aortic stenosis (AS) may occur with preserved or depressed left ventricular ejection fraction (LVEF). Both situations represent the most challenging subset of patients to manage and generally have a poor prognosis. Few and controversial data exist on the outcomes of these patients compared with normal flow-high gradient (NF-HG) AS after transcatheter aortic valve replacement (TAVR). We sought to characterize different transvalvular flow-gradient patterns and to examine their prognostic value after TAVR. We enrolled 1,208 patients with severe AS and categorized as follow: 976 patients NF-HG (mean aortic pressure gradient [MPG] ≥40mm Hg), 107 paradoxical LF-LG (pLF-LG, MPG <40mm Hg, LVEF ≥50%, stroke volume index <35ml/m2), and 125 classical LF-LG (cLF-LG) (MPG <40mm Hg, LVEF <50%, stroke volume index <35ml/m2). When compared with NF-HG and pLF-LG, cLF-LG had a worse symptomatic status (New York Heart Association III to IV 86% vs 62% and 67%, p <0.001), a higher prevalence of eccentric hypertrophy and a higher level of LV global afterload reflected by a higher valvuloarterial impedance. Valvular function after TAVR was excellent over time in all patients. While 30-day mortality (p=0.911) did not differ significantly among groups, cLF-LG had a lower 5-year survival rate (LF-LG 50% vs pLF-LG 62% and NF-HG 68%, p <0.05). cLF-LG was associated with a hazard ratio for mortality of 2.41 (95% confidence interval 1.65 to 3.52, p <0.001). In conclusion, TAVR is an effective procedure regardless of transvalvular flow-gradient patterns. However, special care should be given to characterized hemodynamic of AS, as patients with pLF-LG had similar survival rates than patients with NF-HG, whereas cLF-LG is associated with a twofold increased risk of mortality at 5-year follow-up.

Prognostic Implication of Pulmonary Hypertension in Low-Flow Low-Gradient Aortic Stenosis After Transcatheter Aortic Valve Replacement

Prognostic implications of pulmonary hypertension (PH) in low-flow low-gradient (LG) aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) remains unexplored. We aimed to investigate the impact of baseline and changes in PH after TAVR. In this single-center retrospective study, we included patients who underwent TAVR for low-flow LG AS. Patients were categorized into 2 groups: baseline pulmonary artery systolic pressure (PASP) <46mm Hg (no-to-mild PH) and PASP ≥46mm Hg (moderate-to-severe PH). On the basis of changes in PASP after TAVR, patients were stratified into increased (ΔPASP ≥+5 mm Hg), no change (-4 to +4 mm Hg), and decreased (≤ -5 mm Hg) groups. Primary end point was a composite of all-cause mortality and heart failure rehospitalization. In total, 210 patients were included, 148 in the no-to-mild PH group and 62 in the moderate-to-severe PH group. Median follow-up was 13.2 months. The moderate-to-severe PH group was at an increased risk of composite end point (adjusted hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.8 to 6.9), all-cause mortality (HR 2.4, 95% CI 1.1 to 5.6), and heart failure rehospitalization (HR 8.3, 95% CI 2.9 to 23.7). There were no differences in clinical outcomes among those with increased (32%), no change (28%), and decreased (39%) PASP after TAVR. In conclusion, moderate-to-severe PH at baseline is an independent predictor of worse clinical outcomes in patients with low-flow LG AS who undergo TAVR, and this cohort of patients do not seem to derive the benefits of postoperative reduction of PASP.