Prognostic Impact of High-Molecular-Weight von Willebrand Factor Multimer Ratio in Classical Low-Flow Low-Gradient Aortic Stenosis.

INTRODUCTION: High-molecular-weight (HMW) von Willebrand factor (VWF) multimer deficiency occurs in classical low-flow, low-gradient (LF/LG) aortic stenosis (AS) due to shear force-induced proteolysis. The prognostic value of HMW VWF multimer deficiency is unknown. Therefore, we sought to evaluate the impact of HMW VWF multimer deficiency on clinical outcome. METHODS: In this prospective research study, a total of 83 patients with classical LF/LG AS were included. All patients underwent dobutamine stress echocardiography to distinguish true-severe (TS) from pseudo-severe (PS) classical LF/LG AS. HMW VWF multimer ratio was calculated using densitometric Western blot band quantification. The primary endpoint was all-cause mortality. RESULTS: Mean age was 79 ± 9 years, and TS classical LF/LG AS was diagnosed in 73% (n = 61) and PS classical LF/LG AS in 27% (n = 22) of all patients. Forty-six patients underwent aortic valve replacement (AVR) and 37 were treated conservatively. During a mean follow-up of 27 ± 17 months, 47 deaths occurred. Major bleeding complications after AVR (10/46; 22%) were more common in patients with HMW VWF multimer ratio <1 (8/17; 47%) in comparison to patients with a normal multimer pattern (2/29; 7%) at baseline (p = 0.003). In a multivariable Cox regression analysis, HMW VWF multimer deficiency was a predictor of all-cause mortality (HR: 3.02 [95% CI: 1.31-6.96], p = 0.009) in the entire cohort. This association was driven by higher mortality rates in the AVR group (multivariable-adjusted HR: 9.4; 95% CI 2.0-43.4, p = 0.004). CONCLUSIONS: This is the first study to demonstrate the predictive value of HMW VWF multimer ratio for risk stratification in patients with classical LF/LG AS. HMW VWF multimer deficiency was associated with an increased risk of all-cause mortality and major bleeding complications after AVR.

Prognostic value of transvalvular flow rate in patients with low-gradient severe aortic stenosis: A dobutamine stress echocardiography study.

BACKGROUNDS: There are limited data on the clinical relevance of transvalvular flow rate (Qmean ) at rest (Qrest) and at peak stress (Qstress ) during dobutamine stress echocardiography (DSE) in patients with low-gradient severe aortic stenosis (LG-SAS). METHODS: We retrospectively analyzed the clinical data of patients with LG-SAS who underwent DSE. LG-SAS was defined as an aortic valve (AV) area index of < .6 cm2 /m2 and a mean AV pressure gradient (AVPG) of < 40 mm Hg. The primary endpoint included all-cause death and heart failure hospitalization. RESULTS: Of 100 patients (mean age 79.5 ± 7.3 years; men, 45.0%; resting left ventricular ejection fraction [LVEF] 52.1% ± 15.9%; resting stroke volume index 35.8 ± 7.7 mL/m2 ; Qrest 171.8 ± 34.9 mL/s), the primary endpoint occurred in 51 patients during a median follow-up of 2.84 (interquartile range 1.01-5.21) years. When the study patients were divided into three subgroups based on Qrest and Qstress , the multivariate analysis showed that Qrest < 200 mL/s and Qstress ≥200 mL/s (hazard ratio 3.844; 95% confidence interval 1.143-12.930; p = .030), as well as Qrest and Qstress < 200 mL/s (hazard ratio 9.444; 95% confidence interval 2.420-36.850; p = .001), were significantly associated with unfavorable outcomes with Qrest and Qstress ≥200 mL/s as a reference after adjusting for resting LVEF, resting mean AVPG, chronic kidney disease, New York Heart Association functional class III/IV, and AV replacement. CONCLUSIONS: Flow conditions based on the combination of Qrest and Qstress are helpful for risk stratification in LG-SAS patients.

Moderate aortic stenosis in the dysfunctional ventricle: should it be treated?

Moderate aortic stenosis is associated with a worse prognosis than milder degrees. Pathophysiologically, this condition in a dysfunctional ventricle could lead to a further mechanism of haemodynamic worsening, so its treatment should lead to clinical advantages for the patient. The low risk of complications associated with percutaneous correction of aortic valve disease (transcatheter aortic valve implantation) should also be considered, which would seem to favour an interventional approach even in the aforementioned condition. However, sparse data and small population studies make this approach still controversial. Three randomized controlled trials are underway to shed definitive light on the topic.

Multimodality Imaging in Aortic Stenosis: Beyond the Valve - Focusing on the Myocardium.

Current guidelines of aortic stenosis (AS) management focus on valve parameters, LV systolic dysfunction, and symptoms; however, emerging data suggest that there may be benefit of aortic valve replacement before it becomes severe by present criteria. Myocardial assessment using novel multimodality imaging techniques exhibits subclinical myocardial injury and remodeling at various stages before guideline-directed interventions, which predicts adverse outcomes. This raises the question of whether implementing serial myocardial assessment should become part of the standard appraisal, thereby identifying high-risk patients aiming to minimize adverse outcomes.

Severe low-gradient aortic stenosis: impact of inadequate left ventricular responses to high afterload on diagnosis and therapeutic decision-making.

The fact that nearly 50% of patients with an aortic valve (AV) area < 1.0 cm2, consistent with severe aortic stenosis (AS), can have mean trans-AV pressure gradients < 40 mmHg, consistent with non-severe AS, indicates that "low-gradient" (LG) severe AS, which is often associated with poor prognosis, deserves particular consideration. Inadequate left ventricular (LV) adaptation to severe AV stenosis resulting from preexistent intrinsic myocardial damages and/or maladaptive LV responses to increased afterload are typical features of severe LG-AS. The diagnosis and management of patients with severe LG-AS are particularly challenging because the discrepancy between the AV area and the trans-AV pressure gradient raises doubts concerning the actual severity of AS and therefore also about the necessity of AV replacement (AVR). LG-AS diagnosis requires integrative multimodality evaluation of both the AV and the LV and therapeutic decision-making necessitates careful individual benefit-risk estimation. Although patients with severe LG-AS associated with low trans-AV flow (i.e., stroke volume ≤ 35 ml/m2) have worse outcomes after AVR than those with high-gradient severe AS, even those with reduced LV ejection fraction (LVEF) can have a significant survival benefit particularly by transcatheter AVR. Dobutamine stress echocardiography facilitates distinction between true-severe and pseudo-severe low-flow LG-AS with reduced LVEF. The review aimed to provide an updated theoretical and practical basis for those engaged in this demanding and still current topic due to the new aspects which have emerged in conjunction with both the evolving scientific knowledge about the various LV responses to the increased afterload and the increasing use of the less invasive transcatheter AVR.

How to deal with low-flow low-gradient aortic stenosis and reduced left ventricle ejection fraction: from literature review to tips for clinical practice.

Low-flow low-gradient aortic stenosis (LFLG AS) with reduced left ventricle ejection fraction (LVEF) is still a diagnostic and therapeutic challenge. The aim of this paper is to review the latest evidences about the assessment of the valvular disease, usually difficult because of the low-flow status, and the therapeutic options. Special emphasis is given to the available diagnostic tools for the characterization of LFLG AS without functional reserve at stress echocardiography and to the factors that clinicians should evaluate to choose between surgical aortic valve repair, transcatheter aortic valve implantation, or medical therapy.

Low-gradient magnetic separation of magnetic nanoparticles under continuous flow: Experimental study, transport mechanism and mathematical modelling.

Low-gradient magnetic separation (LGMS) of magnetic nanoparticles (MNPs) has been proven as one of the techniques with great potential for biomedical and environmental applications. Recently, the underlying principle of particle capture by LGMS, through a process known as magnetophoresis, under the influence of hydrodynamic effect has been widely studied and illustrated. Even though the hydrodynamic effect is very substantial for batch processes, its impact on LGMS operated at continuous flow (CF) condition remained largely unknown. Hence, in this study, the dynamical behaviour of LGMS process operated under CF was being studied. First, the LGMS experiments using poly(sodium 4-styrenesulfonate)-functionalized-MNP as modelled particle system were performed through batchwise (BW) and CF modes at different operating conditions. Here BW operation was used as a comparative study to elucidate the transport mechanism of MNP under the similar environment of CF-LGMS process, and it was found out that the convection induced by magnetophoresis (timescale effective is ∼1200 s) is only significant at far-from-magnet region. Hence, it can be deduced that forced convection is more dominant on influencing the transport behaviour of CF-LGMS (with resident time ≤240 s). Moreover, we found that the separation efficiency of CF-LGMS process can be boosted by the higher number of magnets, the higher MNP concentration and the lower flowrate of MNP solution. To better illustrate the underlying dynamical behaviour of LGMS process, a mathematical model was developed to predict its kinetic profile and separation efficiency (with average error of ∼2.6% compared to the experimental results).

Proposal criteria of paradoxical low-flow low-gradient aortic stenosis for predicting prognosis in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Paradoxical low-flow, low-gradient (PLF-LG) aortic stenosis (AS) is associated with poor prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). This study aimed to verify the conventional criteria of PLF-LG AS (left ventricular ejection fraction [LVEF] > 50%, mean aortic valve pressure gradient [AVPG] < 40 mm Hg and stroke volume index [SVI] < 35 ml/m2 by measuring Doppler method) compatible for predicting prognosis in patients undergoing TAVI. MATERIALS AND METHODS: A total of 128 consecutive patients who underwent TAVI for AS with LVEF > 50% were enrolled. The primary endpoint was the hospital readmission due to heart failure (HRHF) and the secondary endpoint was all-cause mortality after hospital discharge. The patients were classified by both the conventional criteria of PLF-LG AS and the proposal criteria of PLF-LG AS if mean aortic valve pressure gradient (AVPG) < 40 mmHg and SVI by measuring Simpson's method < cut off value based on the ROC curve for predicting HRHF. RESULTS: According to the conventional criteria, only 6 patients were diagnosed with PLF-LG AS. However, according to the proposal criteria, 16 patients were diagnosed with PLF-LG AS. Fourteen patients developed HRHF during the follow-up period after TAVI. Based on the ROC curves, SVI by measuring Simpson's method (cut off value = 25 ml/m2) had higher sensitivity and specificity for predicting HRHF (AUC = 0.74, p = 0.0013) than SVI by measuring Doppler method (AUC = 0.63, p = 0.045). The multivariate analysis revealed that PLF-LG AS defined by the proposal criteria (HR: 5.25; 95% CI: 1.60-17.16; p = 0.0073) but not by the conventional criteria was independently associated with HRHF. PLF-LG AS defined by the conventional criteria and the proposal criteria were not associated with all-cause mortality in the univariate analysis. CONCLUSIONS: Our results demonstrated that new criteria of PLF-LG AS defined as SVI < 25 ml/m2 measured by Simpson's method could predict HRHF in patients with severe AS who underwent TAVI.

Unequivocal interpretation of dobutamine stress echocardiography in low-flow, low-gradient aortic stenosis by right parasternal view.

We present the case of a 77-years-old man with aortic valve stenosis (AS) and reduced left ventricular ejection fraction, in whom right parasternal view provided the best hemodynamic evaluation of AS severity during dobutamine stress echocardiography.

The prognostic value of left ventricular dimensions at the time of transcatheter aortic valve replacement: A propensity-matched analysis.

AIMS: In the clinical practice a noteworthy proportion of severe symptomatic aortic stenosis patients presents with low-flow low-gradients features, these having reported a less favorable prognosis even when surgically or transcatheter treated. METHODS AND RESULTS: We retrospectively analyzed the prospectively collected data on 1051 consecutive patients undergone balloon-expandable transcatheter aortic valve replacement at our Institution from January 2008 to January 2020. We divided the population according with a mean aortic gradient (MAG) < or ≥40 mmHg and we performed a propensity-matched analysis based on the Society of Thoracic Surgery Score and age, obtaining two homogeneous groups of 314 patients each (Groups A and B, respectively). We then analyzed the outcomes of the two groups by implementing adjusted Cox models adjusted for significant clinical differences between the two groups, such as sex, ejection fraction, comorbidities and other variables not included in the propensity-matched analysis. The only variable associated with both cardiovascular and all-cause events was an ejection fraction ≤35%. Finally, a sensitivity analysis found that an ejection fraction ≤35% was associated with an increase cardiovascular and all-cause mortality only in patients with an indexed end-diastolic volume >97 ml/m2 (p = .0438 and .3363, respectively). CONCLUSIONS: In our series a MAG <40 mmHg was not found to be per se an independent risk factor for cardiac and all-cause mortality after transcatheter aortic valve replacement. The ejection fraction was found to be an independent risk factor only in the context of enlarged left ventricular dimensions.

Impact of sex on the management and outcome of aortic stenosis patients.

OBJECTIVE: The aim of this study was to assess the impact of sex on the management and outcome of patients according to aortic stenosis (AS) severity. INTRODUCTION: Sex differences in the management and outcome of AS are poorly understood. METHODS: Doppler echocardiography data of patients with at least mild-to-moderate AS [aortic valve area (AVA) ≤1.5 cm2 and peak jet velocity (VPeak) ≥2.5 m/s or mean gradient (MG) ≥25 mmHg] were prospectively collected between 2005 and 2015 and retrospectively analysed. Patients with reduced left ventricular ejection fraction (<50%), or mitral or aortic regurgitation >mild were excluded. RESULTS: Among 3632 patients, 42% were women. The mean indexed AVA (0.48 ± 0.17 cm2/m2), VPeak (3.74 ± 0.88 m/s), and MG (35.1 ± 18.2 mmHg) did not differ between sexes (all P ≥ 0.18). Women were older (72.9 ± 13.0 vs. 70.1 ± 11.8 years) and had more hypertension (75% vs. 70%; P = 0.0005) and less coronary artery disease (38% vs. 55%, P < 0.0001) compared to men. After inverse-propensity weighting (IPW), female sex was associated with higher mortality (IPW-HR: 1.91 [1.14-3.22]; P = 0.01) and less referral to valve intervention (competitive model IPW-HR: 0.88 [0.82-0.96]; P = 0.007) in the whole cohort. This excess mortality in women was blunted in concordant non-severe AS initially treated conservatively (IPW-HR = 1.03 [0.63-1.68]; P = 0.88) or in concordant severe AS initially treated by valve intervention (IPW-HR = 1.25 [0.71-2.21]; P = 0.43). Interestingly, the excess mortality in women was observed in discordant low-gradient AS patients (IPW-HR = 2.17 [1.19-3.95]; P = 0.01) where women were less referred to valve intervention (IPW-Sub-HR: 0.83 [0.73-0.95]; P = 0.009). CONCLUSION: In this large series of patients, despite similar baseline hemodynamic AS severity, women were less referred to AVR and had higher mortality. This seemed mostly to occur in the patient subset with discordant markers of AS severity (i.e. low-gradient AS) where women were less referred to AVR.

Resting echocardiographic predictors for true-severe aortic stenosis in patients with low-gradient severe aortic stenosis: A dobutamine stress echocardiography study.

OBJECTIVE: Dobutamine stress echocardiography (DSE) is not always feasible in patients with low-gradient severe aortic stenosis (LG-SAS), and there are limited data available on the resting echocardiographic predictors for true-severe aortic stenosis (TSAS). This study investigated resting echocardiographic predictors for TSAS. METHODS: Clinical data of 106 LG-SAS patients who underwent DSE were retrospectively analyzed. LG-SAS was defined as an aortic valve area index (AVAi) < .6 cm2 /m2 , and a mean AV pressure gradient < 40 mm Hg. The velocity ratio (VR) was calculated as the peak left ventricular outflow tract velocity/peak AV velocity. TSAS was defined as a projected AVAi < .6 cm2 /m2 . RESULTS: The mean age was 79.3 ± 7.3 years, and 45 (42.5%) were men. The resting AV data were as follows: AVAi, .50 ± .07 cm2 /m2 ; mean AV pressure gradient, 23.0 ± 7.4 mm Hg; and VR, .25 ± .05. The projected AVAi was .58 ± .09 cm2 /m2 , and TSAS was documented in 65 (61.3%) patients. In multivariate analysis, the independent predictors of TSAS were AVAi (p = 0.012) and VR (p = 0.004) with respective best cut-off values of .52 cm2 /m2 and .25 on receiver-operating characteristic curve analysis. According to incremental numbers of the predictors, correct classification percentages of TSAS significantly increased with the Cochran-Armitage trend test (16.2% in no predictors, 65.2% in one predictor, and 95.7 % in two predictors; p < 0.001). CONCLUSIONS: Resting AVAi and VR were independent predictors of TSAS in LG-SAS patients. The true severity might be predictable using the combination of resting parameters.

Moderate gradient severe aortic stenosis: diagnosis, prognosis and therapy.

Aortic stenosis (AS) is defined as severe in the presence of: mean gradient ≥40 mmHg, peak aortic velocity ≥4 m/s, and aortic valve area (AVA) ≤1 cm2 (or an indexed AVA ≤0.6 cm2/m2). However, up to 40% of patients have a discrepancy between gradient and AVA, i.e. AVA ≤1 cm2 (indicating severe AS) and a moderate gradient: >20 and <40 mmHg (typical of moderate stenosis). This condition is called 'low-gradient AS' and includes very heterogeneous clinical entities, with different pathophysiological mechanisms. The diagnostic tools needed to discriminate the different low-gradient AS phenotypes include colour-Doppler echocardiography, dobutamine stress echocardiography, computed tomography scan for the definition of the calcium score, and recently magnetic resonance imaging. The prognostic impact of low-gradient AS is heterogeneous. Classical low-flow low-gradient AS [reduced left ventricular ejection fraction (LVEF)] has the worst prognosis, followed by paradoxical low-flow low-gradient AS (preserved LVEF). Conversely, normal-flow low-gradient AS is associated with a better prognosis. The indications of the guidelines recommend surgical or percutaneous treatment, depending on the risk and comorbidities of the individual patient, both for patients with classic low-flow low-gradient AS and for those with paradoxical low-flow low-gradient AS.

Echocardiographic findings on aortic stenosis: an observational, prospective, and multi-center registry.

BACKGROUND: The aim of this aortic stenosis registry was to investigate the changes of routine echocardiographic indices and strain in patients with moderate-to-severe aortic stenosis over a 6-month follow-up period. METHODS: Our aortic stenosis registry is observational, prospective, multicenter registry of nine countries, with 197 patients with aortic valve area less than 1.5 cm2. The enrolment took place from January to August 2017. We excluded patients with uncontrolled atrial arrhythmias, pulmonary hypertension or cardiomyopathies, as well as those with hemodynamically significant valvular disease other than aortic stenosis. We included patients who did not require intervention and who had a complete follow-up study. RESULTS: In patients with preserved ejection fraction, left ventricular mass has significantly increased between baseline and follow-up studies (218 ± 34 grams vs 253 ± 29 grams, p = 0.02). However, when indexed to body surface area, there was no significant difference. Left ventricular global longitudinal strain significantly decreased (-19.7 ± -4.8 vs (-16.4 vs -3.8, p = 0.01). Left atrial volume was significantly higher at follow-up (p = 0.035). Right ventricular basal diameter and mid-cavity diameter were greater at the follow-up (p = 0.04 and p = 0.035, respectively). Patients with low-flow low-gradient aortic stenosis had significantly lower global longitudinal strain (-12.3% ± -3.9% vs -19.7% ± -4.8%, p = 0.01). CONCLUSION: Left atrial dilatation is one of the first changes to take place in low-flow low-gradient aortic stenosis patients even when left ventricular dimensions and function remains intact. Global longitudinal strain is an important determinant of left ventricular systolic and diastolic dysfunction and right ventricular function is an important parameter of aortic stenosis assessment. Accordingly, our registry has further shed the light on these indices role as multisite follow-up of aortic stenosis.

What Is New in Low Gradient Aortic Stenosis: Surgery, TAVR, or Medical Therapy?

BACKGROUND: A significant proportion of patients with aortic stenosis (AS) have discordance in severity by mean gradient/peak velocity and aortic valve area. Low gradient aortic stenosis (LG-AS) is defined when the aortic valve area is < 1 cm2 consistent with severe AS and mean aortic gradient is < 40 mmHg consistent with non-severe AS. LG-AS represents a diagnostic and therapeutic challenge. PURPOSE OF REVIEW: To summarize the different categories, diagnosis, management, and prognosis of LG-AS. LG-AS is classified as classical (ejection fraction (EF) < 50%, indexed stroke volume (SVi) < 35 ml/m2), paradoxical (EF > 50%, SVi < 35 ml/m2), pseudo-severe (moderate AS with reduced EF), or normal flow low gradient AS. RECENT FINDINGS: Recent findings emphasize the importance of low-dose dobutamine stress echocardiography and CT calcium score in the assessment of aortic valve. In addition, flow reserve (increase in SV > 50%) can be evaluated during dobutamine stress echocardiography and helps predict perioperative prognosis. Patients with LG-AS have better survival with aortic valve replacement (AVR) compared to medical therapy, irrespective of presence or absence of flow reserve. Some recent studies suggest that transcatheter aortic valve replacement (TAVR) may be superior to surgical AVR for patients with a lack of contractile flow reserve or those with paradoxical LG-AS, but further investigation is needed to clarify optimal treatment. The role of TAVR in patients with moderate AS and reduced EF is also under investigation.

Hemodynamic characterization of aortic stenosis states.

Aortic stenosis (AS) has become an increasingly prevalent clinical condition, as a result of the "greying of the population", the widespread application of sophisticated diagnostic tools including non-invasive imaging and invasive techniques, and the advent of minimally invasive surgical and percutaneous valve therapies. The diagnosis of severe AS traditionally has relied on the assessment of the mean transvalvular gradient (ΔPmean ) and aortic valve area (AVA) by either echocardiography or catheterization. However, other hemodynamic variables as flow, pressure recovery, and jet eccentricity also play a major role in determining the final hemodynamic state of AS. Moreover, mismatch between ΔPmean and AVA as in low flow low gradient AS and discordance between catheterization and echocardiographic studies in grading severity of AS have increased the complexity of AS diagnosis. The present case-based treatise emphasizes a multi-modality approach to delineation of the hemodynamic pathophysiology of different AS states. KEY POINTS: Reduction in the aortic valve area, flow across the aortic valve, and direction of the aortic stenosis jet determine the pressure gradient generated across the aortic valve in patients with aortic stenosis. Discordance between echo and catheterization maximum gradients is related to the inherent temporal differences between the times of their acquisition. Discordance between echo and catheterization mean gradients is related to pressure recovery and assumptions in the application of Bernoulli equation to estimate the aortic valve gradient. Pressure recovery relates to the ratio of the aortic valve area and ascending aortic diameter as well as the jet direction. Mismatch between area and gradient criteria for aortic stenosis severity may occur with or without concordance between echocardiographic and catheterization data. Errors of measurement should be excluded prior to assuming any mismatch or discordance between the data. Area gradient mismatch occurs when the aortic valve area is in the severe range, while the gradient is in the non-severe range as in low flow low gradient aortic stenosis. Reverse area gradient mismatch occurs when the gradient is in the severe range, while the aortic valve area is in the non-severe range as in congenital aortic stenosis with an eccentric jet.

Management of aortic valve replacement according to the gradient across symptomatic aortic valve stenosis and its prognostic impact.

BACKGROUND: Treatment strategy for low-gradient (LG) aortic stenosis (AS) remains an unresolved issue. The presence of a low aortic gradient and preserved left ventricular ejection fraction (LVEF) might lead toward the underestimation of aortic stenosis severity and a more conservative management. We sought (a) to describe the nature and timing of intervention according to flow/gradient subgroups in patibents with LG-AS, (2) to determine the factors associated with the decision to intervene, and (c) to describe prognosis. METHODS AND RESULTS: One hundred and ten patients prospectively included in this study underwent a standardized clinical and imaging evaluation at inclusion and at 1-year follow-up. According to aortic flow, gradient and LVEF, patients were divided into 4 groups: LG-normal flow [n = 27], LG-low flow-low LVEF [n = 27], LG-low flow-normal LVEF [n = 16], and high gradient (HG) [n = 40]). 73% of patients underwent AVR 86 ± 59 days after the initial assessment. The HG subgroup had significantly higher intervention rates (P < .001). In multivariable analysis, four parameters were associated with the AVR: aortic gradient (HR 1.52 [1.10-2.11], P = .012), LVEF (HR 0.58 [0.40-0.85], P = .006), atrial fibrillation (HR 0.43 [0.021-0.87], P = .019), and NT-proBNP (HR 0.92[0.86-0.98), P = .008]. Patients operated earlier had better outcomes than those having a delayed AVR (P = .042). LG-AS patients had worse outcomes than HG-AS patients (P < .001). CONCLUSION: Compared to HG-AS, LG-AS is less likely to benefit from an AVR and had a significantly worse outcome. Further interventional studies are needed to investigate the timing of AVR in these patients.

Impact of baseline left ventricular ejection fraction on outcome after transfemoral transcatheter aortic valve implantation in patients with and without low-gradient aortic stenosis.

OBJECTIVES: To evaluate the impact of baseline left ventricular ejection fraction (LVEF) and its interaction with low-gradient aortic stenosis (LGAS) on all-cause mortality after transfemoral aortic valve implantation (TF-TAVI). METHODS: We reviewed mortality data of 624 consecutive single center TF-TAVI patients and categorized LVEF according to current ASE/EACVI recommendations (normal, mildly-, moderately-, and severely abnormal). RESULTS: Baseline LVEF was normal in 336 (53.8%), mildly abnormal in 160 (25.6%), moderately abnormal in 91 (14.6%), and severely abnormal in 37 (5.9%) patients, and 1-year mortality was 19%, 17%, 23%, and 43% (P = 0.002), respectively. Patients with LGAS had a similar 1-year mortality compared to those without LGAS in groups with normal (19% vs 19%, P = 0.899) and mildly abnormal LVEF (16% vs 17%, P = 0.898). One-year mortality of patients with LGAS was significantly greater than in those without LGAS in presence of moderately abnormal LVEF (31% vs 11%, P = 0.022), and it was numerically greater than in those without LGAS in presence of severely abnormal LVEF (48% vs 25%, P = 0.219). In multivariate analysis, only the combination of moderately/severely abnormal LVEF and LGAS predicted increased 1-year mortality (HR: 2.12, 95% CI: 1.4-3.2, P < 0.001). Other variables, including EuroSCORE I did not affect this result. CONCLUSIONS: Moderately/severely abnormal LVEF (≤40%) at baseline is associated with increased mortality after TF-TAVI, especially when the mean transvalvular aortic gradient is <40 mm Hg (LGAS), while outcomes in patients with normal and mildly abnormal LVEF are comparable regardless of the pressure gradient across the native aortic valve. (DRKS00013729).

Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) has been reported in patients with aortic stenosis (AS) but its prevalence and phenotype are not known. We examine elderly patients with severe symptomatic AS undergoing transcatheter aortic valve replacement (TAVR) and determine the prevalence and phenotype of ATTR-CA non-invasively. METHODS AND RESULTS: We performed technetium-99m pyrophosphate (99mTc-PYP) cardiac scintigraphy prospectively on patients who underwent TAVR, to screen for ATTR-CA. Transthoracic echocardiography and speckle-strain imaging were performed. We assessed the association of several parameters with ATTR-CA using multivariable logistic regression and constructed receiver operating curves to evaluate the best predictors of ATTR-CA. Among 151 patients (mean age 84 ± 6 years, 68% men), 16% (n = 24) screened positive for ATTR-CA with 99mTc-PYP scintigraphy. Compared with patients without ATTR-CA, ATTR-CA patients had a thicker interventricular septum (1.3 vs. 1.1 cm, P = 0.007), higher left ventricular (LV) mass index (130 vs. 98 g/m2, P = 0.002), and lower stroke volume index (30 vs. 36 mL/m2, P = 0.009). ATTR-CA patients had advanced diastolic dysfunction with higher E/A ratio (2.3 vs. 0.9, P = 0.001) and lower deceleration time (176 vs. 257 ms, P < 0.0001); impairment in systolic function with lower ejection fraction (48% vs. 56%, P = 0.011), myocardial contraction fraction (26 vs. 41, P < 0.0001), and average of lateral and septal mitral annular tissue Doppler S' (4.0 vs. 6.6 cm/s, P < 0.0001). While ATTR-CA patients had more impaired global longitudinal strain (-12 vs. -16%, P = 0.007), relative apical longitudinal strain was the same regardless of ATTR-CA diagnosis (0.98 vs. 0.98, P = 0.991). Average S' best predicted ATTR-CA in multivariable logistic regression (odds ratio 16.67 per 1 cm/s decrease with AUC 0.96, 95% confidence interval 0.90-0.99, P = 0.002) with a value ≤6 conferring 100% sensitivity for predicting a positive 99mTc-PYP amyloid scan. CONCLUSIONS: Transthyretin cardiac amyloidosis is prevalent in 16% of patients with severe calcific AS undergoing TAVR and is associated with a severe AS phenotype of low-flow low-gradient with mildly reduced ejection fraction. Average tissue Doppler mitral annular S' of < 6 cm/s may be a sensitive measure that should prompt a confirmatory 99mTc-PYP scan and subsequent testing for ATTR-CA. Prospective assessment of outcomes after TAVR is needed in patients with and without ATTR-CA.

[Diagnosis and treatment of aortic valve stenosis]. / Diagnose und Therapie der Aortenklappenstenose.

Aortic valve stenosis (AS) is the most frequently observed valvular heart disease. Once it is symptomatic the mortality rapidly increases. The diagnostic gold standard is transthoracic echocardiography. By measuring the maximum transvalvular velocity, mean transaortic pressure gradient and aortic valve opening area, classification of the type of stenosis can be defined. A differentiation is made between high-gradient AS, low-flow low gradient AS with reduced ventricular ejection fraction (<50%) and the paradoxical low-flow low-gradient AS with preserved ventricular function (≥50%). In some cases, additional diagnostic tools are necessary using dobutamine stress echocardiography, transesophageal echocardiography and cardiac computed tomography. The treatment follows an individualized approach. In cases of indications for valve replacement the multidisciplinary heart team takes into account the patient's age and individual risk for deciding whether an open surgical approach or transcatheter aortic valve implantation is indicated.