Low-gradient Aortic Stenosis Patients Research Articles

Prognostic and therapeutic implications of low aortic valve calcium score in patients with low gradient aortic stenosis.

Low gradient (LG) aortic stenosis (AS) poses a diagnostic challenge. Aortic valve calcium score (AVCS) assessment has emerged as a complementary diagnostic method when echocardiography provides discordant results. However, the diagnostic and prognostic value of AVCS in LGAS has not been thoroughly studied. Our aims were to investigate the prognostic importance of AVCS in LGAS and to assess whether symptomatic patients with LGAS and low AVCS may benefit from aortic valve intervention (AVI). 327 symptomatic patients (78.5±7.3 years, 51% women) with severe AS defined by the aortic valve area who underwent computed tomography for transcatheter aortic valve intervention (TAVI) planning were enrolled. AVCS was measured. AVCS<2000 AU in men and<1200 AU in women was considered low AVCS. 243 patients had high gradient (HG) and 84 had LGAS. Low AVCS was present in 25(10%) of the HG and 34(40%) of the LGAS cases. Over a median follow-up period of 4.9 years, 194 deaths occurred. In multivariate analysis, AVCS was a significant independent predictor of all-cause mortality among HGAS (aHR:2.317; CI:1.104-4.861; p= 0.026), but not among LGAS (aHR:0.848; CI:0.434-1.658; p=0.630) patients. After propensity score matching between patients who underwent AVI and those who were medically treated, AVI (94% TAVI) was a significant and independent predictor of survival among LG AS patients with low AVCS even after adjustment for clinical variables (aHR:0.102, CI:0.028-0.369; p<0.001). The prevalence of low AVCS is much higher in LGAS than in HGAS. In symptomatic severe LGAS low AVCS did not entail a better prognosis. AVI is equally beneficial in LGAS patients with high or low AVCS, similarly to HGAS.

Impact of stroke volume assessment by three-dimensional transesophageal echocardiography on the classification of low-gradient aortic stenosis.

Accurate assessment of flow status is crucial in low-gradient aortic stenosis (AS). However, the clinical implication of three-dimensional transesophageal echocardiography (3DTEE) on flow status evaluation remains unclear. This study aimed to investigate the assessment of flow status using 3D TEE in low-gradient AS patients. We retrospectively reviewed patients diagnosed with low-gradient AS and preserved ejection fraction at our institution between 2019 and 2022. Patients were categorized into low-flow/low-gradient (LF-LG) AS or normal-flow/low-gradient (NF-LG) AS based on two-dimensional transthoracic echocardiography (2DTTE). We compared the left ventricular outflow tract (LVOT) geometry between the two groups and reclassified them using stroke volume index (SVi) obtained by 3DTEE. Among 173 patients (105 with LF-LG AS and 68 with NF-LG AS), 54 propensity-matched pairs of patients were analyzed. 3DTEE-derived ellipticity index of LVOT was significantly higher in LF-LG AS patients compared to NF-LG AS patients (p = 0.012). We assessed the discordance in flow status classification between SVi2DTTE and SVi3DTEE in both groups using a cutoff value of 35ml/m2. The LF-LG AS group exhibited a significantly higher discordance rate compared to the NF-LG AS group, with rates of 50% and 2%, respectively. The optimal cutoff values of SVi3DTEE for identifying low flow status, based on 2DTTE-derived cutoff values, were determined to be 43ml/m2. LVOT ellipticity in low-gradient AS patients varies depending on flow status, and this difference contributes to discrepancies between SVi3DTEE and SVi2DTTE, particularly in LF-LG AS patients. Utilizing SVi3DTEE is valuable for accurately assessing flow status.

The prognostic significance of stroke volume index in low gradient severe aortic stenosis: from the national echo database of Australia.

Approximately 50% of patients with severe aortic stenosis (AS) in clinical practice present with 'low-gradient' haemodynamics. Stroke Volume Index (SVI) is a measure of left ventricular output, with 'normal-flow' considered as > 35ml/m2. The association between SVI and prognosis in severe low-gradient AS (LGAS) in currently not well-understood. We analysed the National Echo Database of Australia (NEDA) and identified 109,990 patients with sufficiently comprehensive echocardiographic data, linked to survival information. We identified 1,699 with severe LGAS and preserved ejection fraction (EF) (≥ 50%) and 774 with severe LGAS and reduced EF. One- and three-year survival in each subgroup were assessed (follow-up of 74 ± 43months), according to SVI thresholds. In patients with preserved EF the mortality "threshold" was at SVI < 30ml/m2; 1- and 3-year survival was worse for those with SVI < 30ml/m2 relative to those with SVI > 35ml/m2 (HR 1.80, 95% CI 1.32-2.47 and HR 1.38, 95% CI 1.12-1.70), while survival was similar between those with SVI 30-35ml/m2 and SVI > 35ml/m2. In patients with reduced EF the mortality "threshold" was 35ml/m2; 1- and 3-year survival was worse for both those with SVI < 30ml/m2 and 30-35ml/m2 relative to those with SVI > 35ml/m2 (HR 1.98, 95% CI 1.27-3.09 and HR 1.41, 95% CI 1.05-1.93 for SVI < 30ml/m2 and HR 2.02, 95% CI 1.23-3.31 and HR 1.56, 95% CI 1.10-2.21 for SVI 30-35ml/m2). The SVI prognostic threshold for medium-term mortality in severe LGAS patients is different for those with preserved LVEF (< 30ml/m2) compared to those with reduced LVEF (< 35ml/m2).

Transcatheter Aortic Valve Replacement in Patients With Reduced Ejection Fraction and Nonsevere Aortic Stenosis.

The potential benefit of transcatheter aortic valve replacement (TAVR) in patients with nonsevere aortic stenosis (AS) and heart failure is controversial. This study aimed to assess outcomes of patients with nonsevere low-gradient AS (LGAS) and reduced left ventricular ejection fraction undergoing TAVR or medical management. Patients undergoing TAVR for LGAS and reduced left ventricular ejection fraction (<50%) were included in a multinational registry. True-severe low-gradient AS (TS-LGAS) and pseudo-severe low-gradient AS (PS-LGAS) were classified according to computed tomography-derived aortic valve calcification thresholds. A medical control group with reduced left ventricular ejection fraction and moderate AS or PS-LGAS was used (Medical-Mod). Adjusted outcomes between all groups were compared. Among patients with nonsevere AS (moderate or PS-LGAS), outcomes after TAVR and medical therapy were compared using propensity score-matching. A total of 706 LGAS patients undergoing TAVR (TS-LGAS, N=527; PS-LGAS, N=179) and 470 Medical-Mod patients were included. After adjustment, both TAVR groups showed superior survival compared with Medical-Mod patients (all P<0.001), while no difference was found between TS-LGAS and PS-LGAS TAVR patients (P=0.96). After propensity score-matching among patients with nonsevere AS, PS-LGAS TAVR patients showed superior 2-year overall (65.4%) and cardiovascular survival (80.4%) compared with Medical-Mod patients (48.8% and 58.5%, both P≤0.004). In a multivariable analysis including all patients with nonsevere AS, TAVR was an independent predictor of survival (hazard ratio, 0.39 [95% CI, 0.27-0.55]; P<0.0001). Among patients with nonsevere AS and reduced left ventricular ejection fraction, TAVR represents a major predictor of superior survival. These results reinforce the need for randomized-controlled trials comparing TAVR versus medical management in heart failure patients with nonsevere AS. URL: https://www. gov; Unique identifier: NCT04914481.

Abstract 12237: Transcatheter Aortic Valve Replacement in Very Low Gradient Aortic Stenosis

Introduction: Transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement is recommended for symptomatic patients with high-gradient aortic stenosis (HGAS) and certain patients with low-flow, low-gradient aortic stenosis (LGAS). While TAVI may be beneficial in LGAS (mean pressure gradient (MPG) &lt;40 mmHg), the outcomes of TAVI in very low-gradient AS (VLGAS) patients (&lt;25 mmHg) is under-reported. Methods: This retrospective cohort study analyzed 1269 patients who underwent TAVI at a multi-disciplinary, tertiary-care center. Patients with severe aortic stenosis were divided into VLGAS (≤25mmHg), LGAS (&gt;25 mmHg up to 40 mmHg) and HGAS groups (≥40 mmHg), using MPG derived from transthoracic echocardiography. Symptom improvement was measured by New York Heart Association (NYHA) functional classification at baseline, 30-days, and 1-year. Mortality and rehospitalization were secondary endpoints. Between group differences were evaluated with chi-squared tests. Results: Patients with VLGAS had improvement in NYHA functional class after TAVI that was similar to those with LGAS and HGAS (figure). While symptom improvement was similar between groups at 30 days (86% in VLGAS, 84% in LGAS and 85% in HGAS, p=0.46), VLGAS was associated with inferior symptom improvement at 1 year (76%, 87%, and 89%, respectively, p&lt;0.01). One-year rehospitalization rates were higher in patients with VLGAS than in patients with LGAS or HGAS (28%, 21%, and 17%, respectively, p =0.014). Mortality at 1-year did not differ between groups (p=0.65). Conclusion: TAVI improves symptoms in most LGAS patients, including those with VLGAS. More VLGAS patients with either no change or worsened symptoms after TAVI may be correlated to increased rehospitalization.

Characteristics and outcomes of normal-flow low-gradient aortic stenosis patients compared to high-gradient aortic stenosis patients undergoing TAVI

Abstract Background Guidelines recommend aortic valve replacement for aortic stenosis (AS) depending on mean pressure gradients (dPmean) and flow status. It is indicated when dPmean is ≥40 mmHg (high-gradient, HG) or when patients have low-flow low-gradient AS. Normal-flow (stroke volume index, SVi &amp;gt;35 ml/m2) low-gradient (dPmean &amp;lt;40 mmHg) (NFLG) AS is subject of scientific debate and severe AS is considered unlikely in current European guidelines. Purpose We hypothesized that NFLG patients are heterogenous, containing a subgroup similar to HG patients in terms of characteristics and outcomes. The purpose of this study was to identify and assess this subgroup by dividing NFLG patients by dPmean. Methods All patients undergoing transcatheter aortic valve implantation (TAVI) at our centre between 2013 and 2019 were analysed and categorised into groups according to dPmean, left-ventricular ejection fraction, and SVi. Among 2,326 patients analysed, 386 patients fulfilled criteria for NFLG AS (dPmean &amp;lt;40 mmHg, LV-EF ≥50%, SVi &amp;gt;35 ml/m2). They were further subdivided into two groups according to the median dPmean and were compared to 956 HG AS patients (dPmean ≥40 mmHg). Groups were compared for baseline characteristics, mortality, and outcomes according to Valve Academic Research Consortium (VARC) 3 definitions. Results Median dPmean was 33 mmHg in NFLG patients. Accordingly, they were split into two groups, with 204 patients above (higher gradient NFLG) and 182 patients below (lower gradient NFLG) this value. Characteristics of lower gradient NFLG patients differed from HG patients in many aspects while they were similar between higher gradient NFLG and HG patients. This was underscored by higher Society of Thoracic Surgeons (STS) scores in lower gradient NFLG compared to the other two groups (Table). Procedural and short-term clinical complications were similar between groups. The VARC-3 composite endpoint of technical failure occurred in 42 HG (4.4%), 12 higher gradient NFLG (5.9%), and 5 lower gradient NFLG patients (2.7%, p=0.32). The rates of the VARC-3 composite endpoint of device failure at 30 days were 108 patients (11.3%), 21 patients (10.3%), and 17 patients (9.3%), respectively (p=0.71). At follow-up, symptoms of patients from all three groups improved equally by at least one New York Heart Association class (p=0.47). Hazard ratio (HR) for 3-year mortality for all NFLG patients vs. HG patients was 1.4 [95% confidence interval, CI, 1.1–1.8]. Estimated 3-year all-cause mortality was significantly higher in lower gradient NFLG compared to HG patients, whereas mortality rate of higher gradient NFLG was similar to HG (Figure). Conclusions The data show that a large subgroup of NFLG patients has characteristics similar to those of HG patients, with similar clinical and procedural outcomes and comparable mortality rates. If severe AS was identified as the main clinical problem in this subgroup, aortic valve replacement can be justified. Funding Acknowledgement Type of funding sources: None.

Imaging Challenges in Patients with Severe Aortic Stenosis and Heart Failure: Did We Find a Way Out of the Labyrinth?

Aortic stenosis (AS) is the most frequent degenerative valvular disease in developed countries. Its incidence has been constantly rising due to population aging. The diagnosis of AS was considered straightforward for a very long time. High gradients and reduced aortic valve area were considered as “sine qua non” in diagnosis of AS until a growing body of evidence showed that patients with low gradients could also have severe AS with the same or even worse outcome. This completely changed the paradigm of AS diagnosis and involved large numbers of parameters that had never been used in the evaluation of AS severity. Low gradient AS patients may present with heart failure (HF) with preserved or reduced left ventricular ejection fraction (LVEF), associated with changes in cardiac output and flow across the aortic valve. These patients with low-flow low-gradient or paradoxical low-flow low-gradient AS are particularly challenging to diagnose, and cardiac output and flow across the aortic valve have become the most relevant parameters in evaluation of AS, besides gradients and aortic valve area. The introduction of other imaging modalities in the diagnosis of AS significantly improved our knowledge about cardiac mechanics, tissue characterization of myocardium, calcium and inflammation burden of the aortic valve, and their impact on severity, progression and prognosis of AS, not only in symptomatic but also in asymptomatic patients. However, a variety of novel parameters also brought uncertainty regarding the clinical relevance of these indices, as well as the necessity for their validation in everyday practice. The aim of this review is to summarize the prevalence of HF in patients with severe AS and elaborate on the diagnostic challenges and advantages of comprehensive multimodality cardiac imaging to identify the patients that may benefit from surgical or transcatheter aortic valve replacement, as well as parameters that may help during follow-up.

Impact of left ventricular fibrosis and longitudinal systolic strain on outcomes in low gradient aortic stenosis

Abstract Background The clinical utility of comprehensive cardiac magnetic resonance (CMR) for the assessment of myocardial structure and function remains unknown in patients with low gradient (LG) aortic stenosis (AS). Purpose This study sought to compare CMR characteristics of myocardial structure and function according to different flow / gradient patterns of AS: classical low flow LG (LFLG); paradoxical LFLG; normal flow LG; and high gradient, and to evaluate their impact on the outcomes of these patients. Methods International multicentric prospective study included 147 patients with LG moderate to severe AS and 18 patients with high gradient severe AS who underwent comprehensive CMR evaluation of left ventricular global longitudinal strain (LVGLS), extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). Results Patients with classical LFLG (n=90) had more LV adverse remodeling and impaired longitudinal function including higher ECV, and higher LGE and volume, and worst LVGLS, compared to other patterns of AS. Over a median follow-up of 2-years, 43 deaths and 48 composite outcomes of death or heart failure hospitalization occurred in LG AS patients. As LVGLS or ECV worsened, risks of adverse events also increased (per tertile of LVGLS: HR [95% CI] for mortality, 1.50 [1.02–2.20]; p=0.04; HR [95% CI] for composite outcome, 1.45 [1.01–2.09]; p&amp;lt;0.05) (per tertile of ECV: HR [95% CI] for mortality, 1.63 [1.07–2.49]; p=0.02; HR [95% CI] for composite outcome, 1.54 [1.02–2.33]; p=0.04). LGE presence was also associated with higher mortality (HR [95% CI], 2.27 [1.01–5.11]; p&amp;lt;0.05) and risk of the composite outcome (HR [95% CI], 3.00 [1.16–7.73]; p=0.02). The risk of all-cause death and of the composite outcome increased in proportion to the number of impaired components (i.e. LVGLS, ECV and LGE) (Figure) with and without adjustment for age, true severe AS, classical LFLG, and aortic valve replacement as a time-varying covariate. Conclusions In this international multicentric study of LG AS, comprehensive CMR assessment of myocardial structure and function provides independent prognostic value that is cumulative and incremental to clinical and echocardiographic characteristics. Funding Acknowledgement Type of funding sources: None.

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

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. Sex differences in the management and outcome of AS are poorly understood. 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. 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). 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.

Prognostic significance of vascular and valvular calcifications in low- and high-gradient aortic stenosis.

In low-gradient aortic stenosis (LGAS), the high valvulo-arterial impedance observed despite low valvular gradient suggests a high vascular load. Thoracic aortic calcifications (TACs) and valvular aortic calcifications (VACs) are, respectively, surrogates of aortic load and aortic valvular gradient. The aim of this study was to compare the respective contributions of TAC and VAC on 3-year cardiovascular (CV) mortality following TAVI in LGAS vs. high-gradient aortic stenosis (HGAS) patients. A total of 1396 consecutive patients were included. TAC and VAC were measured on the pre-TAVI CT-scan. About 435 (31.2%) patients had LGAS and 961 (68.8%) HGAS. LGAS patients were more prone to have diabetes, coronary artery disease (CAD), atrial fibrillation (AF), and lower left ventricular ejection fraction (LVEF), P<0.05 for all. During the 3 years after TAVI, 245(17.8%) patients experienced CV mortality, 92(21.6%) in LGAS and 153(16.2%) in HGAS patients, P=0.018. Multivariate analysis adjusted for age, gender, diabetes, AF, CAD, LVEF, renal function, vascular access, and aortic regurgitation showed that TAC but not VAC was associated with CV mortality in LGAS, hazard ratio (HR) 1.085 confidence interval (CI) (1.019-1.156), P=0.011, and HR 0.713 CI (0.439-1.8), P=0.235; the opposite was observed in HGAS patients with VAC but not TAC being associated with CV mortality, HR 1.342 CI (1.034-1.742), P=0.027, and HR 1.015 CI (0.955-1.079), P=0.626. TAC plays a major prognostic role in LGAS while VAC remains the key in HGAS patients. This confirms that LGAS is a complex vascular and valvular disease.

Non-invasive quantitative characterization of aortic valve tissue composition from computed tomography angiography improves patient risk stratification in transcatheter aortic valve implantation

Abstract Background Computed tomography angiography (CTA) performed for procedural planning of transcatheter aortic valve implantation (TAVI) can be used for a more complete characterization of aortic valve tissue beyond calcium assessment. Combining quantitative data on both noncalcified and calcified tissues may improve differentiation of aortic stenosis (AS) subtypes and prognostication post-TAVI. Purpose We sought to noninvasively assess aortic valve tissue composition with quantitative cardiac CTA in patients with AS and its prognostic vaalue in those who underwent TAVI. Methods In 185 consecutive AS patients in a prospective registry who underwent cardiac CTA before TAVR and 90 matched controls with normal aortic valves, non-luminal aortic valve tissue were identified using semi-automated software as non-calcified (low-attenuation [−30 to 30 Hounsfield Units (HU)], fibro-fatty (31 to 130 HU), fibrous (131 to 350 HU) and calcified (&amp;gt;650 HU) tissue; with total tissue as (non-calcified + calcified components). Volumes of each component and composition [(tissue component volume/total tissue volume) ×100%] were quantified. The association of aortic valve composition and clinical outcomes post-TAVI including all-cause mortality was evaluated using Valve Academic Research Consortium (VARC)-2 definitions. Results AS patients had greater aortic valve tissue volume (median 2000.2, vs 527.8 mm3, p&amp;lt;0.001) with a higher calcified tissue composition (41.8% vs 3.4%, p&amp;lt;0.001) compared to controls. Total aortic valve tissue (noncalcified and calcified) volume yielded the highest area under the operating curve (AUC) for diagnosing severe AS (0.93,95% CI:0.93–0.99) as compared to calcified tissue volume alone (0.87,95% CI:0.81–0.94, p=0.002). Low-flow low-gradient AS was associated with increase in total tissue volume compared to controls (1515.3 vs 527.8 mm3, p&amp;lt;0.001), with lower volumes of calcified tissue than high-gradient AS (412.5 vs 829.6 mm3, p&amp;lt;0.001). Device success was achieved in 88% (164 of 185) patients and prevalence of moderate or severe paravalvular leak was 3.8%, however no differences between in aortic valve composition were observed in patients with and without device success. Early safety endpoints occurred in 16.1% (29 of 180) patients and 30-day all-cause mortality was 4.4%. Whereas only calcified tissue volume was related to VARC-2 early safety, AUC for prediction of 30-day mortality post-TAVI was 0.793 (95% CI:0.685–0.901) for total tissue volume and 0.776 (95% CI:0.676–0.876) for calcified tissue volume. Conclusions Quantitative CTA assessment of aortic valve tissue volume and composition can improve identification of high-gradient AS and low-flow low-gradient AS patients referred for TAVI and predict 30-day mortality post-TAVI. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute (NHLBI)

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

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. 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. 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). 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.

Low gradient aortic stenosis and TAVI: The differential prognostic value of valvular and aortic calcifications may traduce a particular pathophysiology

Low gradient aortic stenosis (LGAS) is still poorly understood. The valular aspect may be less prominent than in the other forms of aortic stenosis (AS) and intertwined with other aspects such as vascular ones. The severity of the valvular disease was assessed from aortic valvular calcifications (VAC) and that of aorta from thoracic aortic calcifications (TAC). To assess the prognostic significance of VAC and TAC in patients with and without LGAS treated by TAVI. Ancillary study of the C4CAPRI trial including 1282 consecutive patients from 4 French hospitals. The primary outcome was 3 years CV mortality after TAVI. 397 (31%) had a LGAS. They were more frequently men, younger, with atrial fibrillation (AF), and lower left ventricular ejection fraction (LVEF), P < 0.05 for all. VAC was lower in LGAS (1.05 cm 3 ± 0.7 vs. 0.75 cm 3 ± 0.5), P < 0.001, while the opposite was noticed for TAC, (3.1 cm 3 ± 3 vs. 3.7 cm 3 ± 3.7), P = 0.01. After 3 years, 227 (17.7%) patients died from CV causes; respectively 85(21.4%) and 142(16.1%) patients with and without LGAS, P = 0.02. Multivariate analysis was adjusted for TAC, VAC, age, gender, AF, LVEF, pulmonary systolic pressures, history of diabetes, chronic respiratory disease, renal insufficiency and peripheral vascular disease. In LGAS patients TAC HR 1.090 CI (1.02–1.16) but not VAC was a predictor of CV mortality while in patients without LGAS, VAC HR 1.377 CI (1.049–1.809) but not TAC was associated with CV mortality. The present study confirms that valvular disease seems less prevailing in LGAS patients than in other forms of AS. On the other hand, vascular after load, estimated by TAC, conveys a major prognostic information in this subgroups. This has clinical impact: VAC may be a marker of early and periprocedural mortality and aortic regurgitation in non-LGAS patients, while TAC may continue to increase left ventricular after load in patients with LGAS whom LVEF is often impaired.

P907Respective pronostic value of the valvular aortic calcifications and the thoracic aorta calcifications in patients with and without low gradient aortic stenosis after TAVI

Abstract Background Both the valvular aortic calcifications (VAC) and the thoracic aorta calcifications (TAC) have a prognostic impact in patients with aortic stenosis. Their respective prognostic values in patients with and without low gradient aortic stenosis (LGAS) remain unknown after TAVI. Objectives To assess the prognostic significance of VAC and TAC in patients with and without LGAS regarding cardiovascular mortality after 3 years follow-up. Methods The CAPRI-LGAS is an ancillary study of the C4CAPRI trial (NCT02935491) including 1282 consecutive TAVI patients. Calcifications were measured on pre-TAVI CT. The primary outcome was defined as cardiovascular mortality 3 years after TAVI. Results Among the 1282 patients, 397 (31%) had a LGAS. Compared to the other patients, LGAS patients were more prone to be men, younger, with atrial fibrillation, and lower left ventricular ejection fraction (LVEF), p&lt;0.05 for all. No statistically significant difference was noticed for pulmonary systolic pressures, history of diabetes, chronic respiratory disease, renal insufficiency or peripheral vascular disease. VAC was lower in LGAS compared to non-LGAS patients (1.05 cm3±0.7 vs 0.75 cm3±0.5), p&lt;0.001, the contrary was noticed for TAC, (3.1 cm3±3 vs 3.7 cm3±3.7), p=0.011. After 3 years follow-up, 227 (17.7%) patients died from cardiovascular causes; respectively 85 (21.4%) and 142 (16.1%) patients with and without LGAS, p=0.02. In univariate analysis, in LGAS patients each increase of 1cm3 TAC was associated with cardiovascular mortality while VAC was not, respectively Hazard Ratio (HR) 1.07 and confidence interval (CI) (1.023–1.119) p=0.003, and HR 0.822 CI (0.523–1.292), p=0.39. In patients without LGAS both TAC and VAC were associated with mortality, respectively HR 1.054 CI (1.006–1.104), p=0.028 and HR 1.363 CI (1.092–1.701), p=0.006. Multivariate analysis was adjusted for TAC, VAC, age, gender, atrial fibrillation, and LVEF. In LGAS patients TAC but not VAC was still a predictor of cardiovascular mortality, respectively HR 1.092 CI (1.031–1.158), p=0.003, and HR 0.743 CI (0.464–1.191), p=0.21. In patients without LGAS TAC was no more associated with cardiovascular mortality while VAC was, respectively HR 1.306 CI (1.024–1.666), p=0.031, and HR 1.038 CI (0.985–1.094), p=0.161. When further adjusting on pulmonary systolic pressures, history of diabetes, chronic respiratory disease, renal insufficiency and peripheral vascular disease, the results remained similar ie in LGAS patients, TAC HR 1.090 CI (1.022–1.162), p=0.009 while in patients without LGAS VAC HR 1.377 CI (1.049–1.809), p=0.021. Conclusions The present study shows that VAC and TAC involve different prognostic information in patients with and without LGAS after TAVI. While VAC may be a marker of early and periprocedural mortality and aortic regurgitation in non-LGAS patients, TAC may continue to be harmful and increase afterload in patients with LGAS whom LVEF is often impaired.

1139Prognostic impact of aortic valve replacement in contemporary low-gradient aortic stenosis patients with lack of contractile reserve

1139Prognostic impact of aortic valve replacement in contemporary low-gradient aortic stenosis patients with lack of contractile reserve

Dilemma in the therapeutic management of low-gradient aortic stenosis.

Grading of aortic stenosis is essential in aortic stenosis management patients. However, despite clear thresholds provided in the guidelines, up to 30% of patients have discordant grading of aortic stenosis. The management of patients with low gradients/velocity despite tight aortic valve area is challenging. Recent studies demonstrated that patients with or without low flow may have a severe aortic stenosis despite a low gradient. Moreover, aortic valve replacement has been shown to improve outcome in low-gradient aortic stenosis patients with or without low flow. Finally, measurement of aortic valve calcification by multidetector computed tomography is an important tool to assess aortic stenosis severity in these patients. The presence of a low gradient/velocity despite a tight aortic valve area could be linked to low ejection fraction or low flow with preserved ejection fraction but also with normal flow and normal ejection fraction. In each situation, aortic stenosis could be truly severe or pseudosevere, and the severity of aortic stenosis has to be accurately evaluated for clinical decision-making. Nowadays, two types of interventions are available: surgical and transcatheter aortic valve replacement, whereas conservative management should be considered as a palliative treatment in patients with proven severe aortic stenosis and symptoms or left ventricle dysfunction.

Abstract 13803: Integration of Stroke Volume Index Into Clinical Decision Making for Patients With Suspected Severe Aortic Stenosis and Preserved Ejection Fraction: A Systematic Review of Evidence and Meta-Analysis

Introduction: The 2014 ACC/AHA valvular disease guidelines recommend estimation of stroke volume index (SVI) by echocardiography in patients with suspected low-gradient severe aortic stenosis (SAS) and preserved left ventricular ejection fraction. We explored the evidence base for this recommendation by comparing the natural history of the disease in subgroups of low gradient aortic stenosis patients with high gradient patients. Methods: Pubmed, Embase and Scopus databases were searched for all studies that have compared natural history of SAS with preserved LVEF in flow-gradient patterns. We studied the following 3 groups: high gradient (HG), low-flow low-gradient (LFLG), and normal-flow low-gradient (NFLG). Random effects model was used to pool individual study results. The end-point was long-term all-cause mortality. Results: A total of 7 studies with 3,954 patients fulfilled the criteria. Compared to HG SAS, both LFLG and NFLG patients had a higher burden of comorbidities such as atrial fibrillation, coronary artery disease, and hypertension. Also, end-diastolic volume index was smaller for LFLG patients and indexed aortic valve area larger for NFLG patients. All-cause mortality was similar between HG and LFLG groups [Relative risk (RR): 1.27, 95% confidence interval (CI): 0.85 -1.91, p=0.24], while patients with NFLG had significantly lower all-cause mortality compared to HG group [RR: 0.63, 95% CI: 0.44-0.89, p=0.009]. Conclusions: Compiled evidence supports using SVI in patients with suspected low gradient SAS. All analyses revealed high heterogeneity and further high-quality studies are necessary.

Abstract 9883: Impact of Low Transvalvular Gradient on Early and Late Outcomes After Aortic Valve Replacement for Aortic Stenosis

Background: Few data are available concerning the results of aortic valve replacement (AVR) for low-gradient severe aortic stenosis (AS). Aim of this study was to assess the hypothesis that low-gradient is an independent predictor of early and late results after AVR. Methods: We retrospectively analyzed a series of 340 consecutive AS patients (area≦1.0cm 2 ) who underwent AVR from 2002 to 2012. Low-gradient AS was defined by the mean transvalvular gradient &lt;40mmHg (n=68, 20%). The outcome measures included hospital mortality, major postoperative complication, prolonged length of hospital stay, and late survival. Results: Hospital mortality was 3.2% (n=11) (low-gradient 8.8%; high-gradient 1.8%; p=0.01). Low-gradient AS was an independent predictor for hospital mortality (odds ratio [OR] 6.0, 95% confidence interval [CI]: 1.6 to 21.2, p=0.006), but did not predict any postoperative major complication. NYHA class III/IV was another independent predictor of hospital mortality (OR 19.3, 95%CI: 2.4 to 155.1, p=0.005). In the patients with low-gradient AS who were in NYHA class III/IV (n=25), hospital mortality was significantly higher (24%) compared to those in NYHA class II (n=43, hospital mortality 0%). Multivariable predictors of late mortality (excluding hospital death) included NYHA class III/IV (OR 9.6, 95%CI: 1.2 to 76.7, p=0.03) and creatinine &gt;2mg/dl (OR 6.9, 95%CI: 2.1 to 22.8, p=0.002). Low-gradient was no longer a risk of late mortality in operative survivors. The survival rate at 7 years after AVR was 84±10% in low-gradient and 95±2% in high-gradient patients (p=0.42). We also calculated propensity score for low-gradient status (C-statistic: 0.71), and 37 low-gradient were matched to 41 high-gradient patients. No statistically significance was observed in late survival between propensity matched low and high-gradient patients (83% vs 95% at 7 years, p=0.86). Conclusions: Low-gradient AS was an independent predictor of increased hospital mortality, but did not predict late mortality in operative survivors. Surgical risk was very high in low-gradient patients with advanced NYHA class. However, AVR could be performed safely if low-gradient AS patients were in NYHA class II, and good long-term survival was seen in operative survivors.

Differential left ventricular remodelling and longitudinal function distinguishes low flow from normal-flow preserved ejection fraction low-gradient severe aortic stenosis

There is uncertainty in identifying patients with severe aortic stenosis (AS) with preserved left ventricular (LV) ejection fraction, low flow, and low gradients (LFLG). Prior studies propose that these patients demonstrate significant concentric remodelling and decreased survival, while others suggest that they have features and survival similar to moderate AS. We compared the clinical characteristics, echocardiographic features, and overall survival of LFLG AS patients (n = 38) to those with normal-flow, low-gradient (NFLG) severe AS (n = 75) and moderate AS (n = 70). Low-flow, low-gradient patients had the lowest end-diastolic volume index (43 vs. 54 vs. 54 mL/m², P < 0.001), highest relative wall thickness (RWT) (60 vs. 49 vs. 48%, P < 0.001), and lowest septal mitral annular displacement (1.0 vs. 1.5 vs. 1.5 cm, P < 0.001). New York Heart Association (NYHA) class III/IV symptoms were the most frequent in the LFLG group (29 vs. 11 vs. 3%, P < 0.001). Survival at 3 years was significantly lower in LFLG compared with NFLG (P = 0.006) and moderate AS (P = 0.002), but not different between NFLG and moderate AS (P = 0.49). Higher NYHA classification (HR 1.77, 95% CI 1.22-2.57), RWT > 50% (HR 3.28, 95% CI 1.33-8.1), and septal displacement <1.1 cm (HR 3.93, 95% CI 1.96-7.82) but not low flow were independent predictors of survival in Cox proportional hazards analysis. Preserved ejection fraction, LFLG AS patients exhibit marked concentric remodelling and impaired longitudinal functional-features that predict their poor long-term survival. Normal-flow, low-gradient AS patients have outcomes similar to moderate AS.

Low-flow, low-gradient aortic stenosis: from evaluation to treatment

Valve replacement improves symptoms and survival in symptomatic severe aortic stenosis. Low-flow, low-gradient aortic stenosis, however, is an especially challenging subset as valve replacement has a significant risk, and may fail to alleviate symptoms or improve left ventricular function. This article reviews the potential problems in evaluating aortic stenosis severity in low-flow, low-gradient aortic stenosis, the utility of dobutamine challenge to identify patients most likely to benefit from surgery, and the factors predicting patient outcome. Low-flow, low-gradient aortic stenosis consists of a heterogeneous group of patients with 'true' severe aortic stenosis, in whom afterload mismatch results from a severely stenotic valve; and 'pseudo-severe' aortic stenosis, where the valve is only mildly or moderately stenotic, but appears severe due to limitations in determining disease severity under low-flow conditions. Valve replacement is likely to benefit the former group, but may have little benefit to the latter. Dobutamine challenge can distinguish 'true' and 'pseudo-severe' aortic stenosis, and can evaluate contractile reserve, one of the strongest predictors of patient outcome. Strategies to avoid prosthesis-patient mismatch should be considered to optimize postoperative outcome. Dobutamine challenge can identify low-flow, low-gradient aortic stenosis patients most likely to benefit from valve replacement and provides important prognostic information on the operative risks and long-term outcome.