Low-flow Low-gradient Severe 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.

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.

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 <1.0cm2 at peak dobutamine stress levels; moderate AS was diagnosed when resting AVA was ≥1.0cm2 and peak velocity was < 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 (<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

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 <1.0 cm2), transaortic gradients (mean gradient< 40 mmHg) and low flow rate (Q ≤210 ml/sec), to confirm the diagnosis of LFLGAS and preserved LVEF (>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<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.

Transcatheter Aortic Valve Implantation with balloon-expandable valve in low-flow low-gradient severe aortic stenosis in Nepal

Transcatheter aortic valve implantation is the most preferred treatment of aortic stenosis in elderly patients at high surgical risk; however, few data exist on the adoption of transcatheter aortic valve implantation for the management of low-flow, low-gradient severe aortic stenosis patients. We present a recent case experience with a 77-year-old man suffering from low-flow, low-gradient, symptomatic severe aortic stenosis with concomitant coronary artery lesions in the left anterior descending and right coronary arteries. He was treated successfully with balloon-expandable transcatheter aortic valve implantation after the percutaneous coronary intervention of the left anterior descending artery and right coronary artery lesion. Post-procedural and 30-day follow-ups showed good functional and hemodynamic improvements with the mean aortic gradient of 3 mmHg (baseline: 30 mmHg) without residual paravalvular leakage. Our first experience with a balloon-expandable transcatheter valve was satisfactory as we observed clinical efficacy and good performance of the balloon-expandable transcatheter aortic valve in low-flow, low-gradient, symptomatic severe AS patients.

Prevalence and Outcomes of Low-Gradient Severe Aortic Stenosis-From the National Echo Database of Australia.

BackgroundThe prevalence and outcomes of the different subtypes of severe low‐gradient aortic stenosis (AS) in routine clinical cardiology practice have not been well characterized.Methods and ResultsData were derived from the National Echocardiography Database of Australia. Of 192 060 adults (aged 62.8±17.8 [mean±SD] years) with native aortic valve profiling between 2000 and 2019, 12 013 (6.3%) had severe AS. Of these, 5601 patients (47%) had high‐gradient and 6412 patients (53%) had low‐gradient severe AS. The stroke volume index was documented in 2741 (42.7%) patients with low gradient; 1750 patients (64%) with low flow, low gradient (LFLG); and 991 patients with normal flow, low gradient. Of the patients with LFLG, 1570 (89.7%) had left ventricular ejection fraction recorded; 959 (61%) had paradoxical LFLG (preserved left ventricular ejection fraction), and 611 (39%) had classical LFLG (reduced left ventricular ejection fraction). All‐cause and cardiovascular‐related mortality were assessed in the 8162 patients with classifiable severe AS subtype during a mean±SD follow‐up of 88±45 months. Actual 1‐year and 5‐year all‐cause mortality rates varied across these groups and were 15.8% and 49.2% among patients with high‐gradient severe AS, 11.6% and 53.6% in patients with normal‐flow, low‐gradient severe AS, 16.9% and 58.8% in patients with paradoxical LFLG severe AS, and 30.5% and 72.9% in patients with classical LFLG severe AS. Compared with patients with high‐gradient severe AS, the 5‐year age‐adjusted and sex‐adjusted mortality risk hazard ratios were 0.94 (95% CI, 0.85–1.03) in patients with normal‐flow, low‐gradient severe AS; 1.01 (95% CI, 0.92–1.12) in patients with paradoxical LFLG severe AS; and 1.65 (95% CI, 1.48–1.84) in patients with classical LFLG severe AS.ConclusionsApproximately half of those patients with echocardiographic features of severe AS in routine clinical practice have low‐gradient hemodynamics, which is associated with long‐term mortality comparable with or worse than high‐gradient severe AS. The poorest survival was associated with classical LFLG severe AS.

Relative prevalence and outcomes of low gradient severe aortic stenosis in routine clinical practice

Abstract Background The prevalence and outcomes of low-gradient severe aortic stenosis (AS), in particular low-flow low-gradient (LFLG) severe AS, have not been well characterized. Objectives We sought to delineate the relative prevalence and outcomes of patients with low-gradient severe AS in routine clinical cardiology practice. Methods Data were derived from the National Echocardiography Database of Australia (NEDA), a national multicentre clinical registry with data linkage to mortality. A total of 192,060 adults with native aortic valve profiling from 2000–2019 were identified, of whom 12,013 (6.3%) had severe AS (aged 75.3±13.1 years, 53.5% men). Severe AS subtypes were determined using standard echocardiographic criteria. All-cause and cardiovascular-related mortality were assessed on an adjusted basis (age and sex) in 8,162 patients with classifiable severe AS subtypes, during mean follow-up of 88±45 months. Additionally, rates of recorded Aortic Valve Replacement (AVR) during follow-up were compared between AS groups. Results 5,601 patients (47%) had high-gradient and 6,412 patients (53%) had low-gradient severe AS. In the low-gradient group, Stroke Volume Index data was recorded in 2,741 patients; 1,750 (64%) had LFLG and 991 (36%) had normal-flow low-gradient (NFLG). For LFLG patients, 1,570 had LV ejection fraction recorded; 959 (61%) had paradoxical LFLG and 651 (39%) had classical LFLG. Adjusted 5-year cardiovascular mortality rates were 28% in high-gradient, 24% in NFLG, 27% in paradoxical LFLG and 50% in classical LFLG patients (p<0.001). Rates of recorded AVR per mean follow-up years were 5.2% for high-gradient, 4.0% for NFLG, 3.1% for classical LFLG and 2.4% for paradoxical LFLG severe AS (p<0.001). Conclusions Approximately half the subjects with echocardiographic features of severe AS in routine clinical practice have low-gradient haemodynamics, associated with long-term mortality comparable to or worse than high-gradient severe AS. The poorest survival was associated with classical LFLG severe AS. Funding Acknowledgement Type of funding sources: None. Summary illustration5 year mortality curves

Cardiac damage staging classification and prognosis in low flow low gradient severe aortic stenosis

Abstract Introduction There are currently no established prognostic models for low-flow, low-Gradient (LFLG) severe aortic stenosis (AS). The Cardiac Damage Staging Classification, has been validated as a clinically useful prognostic tool in high-gradient severe AS, but not specifically in LFLG severe AS. Objective To assess and confirm the prognostic utility of the Cardiac Damage Staging Classification, in LFLG severe AS patients. Methods We analysed data from the National Echocardiography Database of Australia (NEDA), a national multicentre registry with individual data linkage to mortality. Of 192,060 adults (aged 62.8±17.8 years) with comprehensive ultrasound profiling of the native aortic valve studied between 2000–2019, 12,013 (6.3%) had severe AS. Based on standard echocardiographic parameters, 611 classical and 959 paradoxical LFLG patients were identified. Mean follow-up was 70±41 months. All-cause and cardiovascular-related mortality were assessed for each LFLG group on an adjusted basis (age and sex), according to cardiac damage classification staging. Results Paradoxical LFLG patients were younger (mean age 74.3 vs 76.2, p=0.006) and more often female (62.8% vs 36.3%, p<0.001). Classical LFLG patients had greater associated cardiac damage at diagnosis (76% vs. 49%, for Stage ≥2, p<0.001). Compared to Stage 0 paradoxical LFLG patients, adjusted 1- and 5-year cardiovascular-related mortality was 200% (HR 2.82, 95% CI 1.12–7.11) and 120% (HR 2.42, 95% CI 1.46–4.02) higher in Stage 2 patients and 350% (HR 4.23, 95% CI 1.68–10.63) and 175% (HR 3.18, 95% CI 1.90–5.34) higher in Stage 3/4 patients, respectively. Compared to Stage 1 classical LFLG patients, adjusted 1- and 5-year cardiovascular-related mortality was 58% (HR 1.66, 95% CI 0.95–2.90) and 24% (HR 1.35, 95% CI 0.91–1.99) higher in Stage 2 patients and 125% (HR 2.48, 95% CI 1.43–4.28) and 52% (HR 1.87, 95% CI 1.26–2.78) higher in Stage 3/4 patients, respectively. Conclusion In patients with LFLG severe AS identified by echocardiography, increasing severity denoted by the cardiac damage staging classification is strongly associated with increasing medium- to long-term mortality. Funding Acknowledgement Type of funding sources: None. Stages + Classical LFLG 5 year mortalityParadoxical LFLG 5 year mortality curves

Cardiac Damage Staging Classification Predicts Prognosis in All the Major Subtypes of Severe Aortic Stenosis: Insights from the National Echo Database Australia

There are currently no established prognostic models for "low-gradient" severe aortic stenosis (AS), including those with low-flow, low-gradient (LFLG) or normal-flow, low-gradient (NFLG) severe AS. The "cardiac damage staging classification" has been validated as a clinically useful prognostic tool for high-gradient severe AS but not yet for these other common subtypes of severe AS, LFLG and NFLG. The authors analyzed data from the National Echo Database of Australia, a large national, multicenter registry with individual data linkage to mortality. Of 192,060 adults (mean age, 62.8±17.8years) with comprehensive ultrasound profiling of the native aortic valve studied between 2000 and 2019, 12,013 (6.3%) had severe AS. On the basis of standard echocardiographic parameters, 5,601 patients with high-gradient, 611 with classical and 959 with paradoxical LFLG, and 911 with NFLG severe AS were identified. Mean follow-up was 88±45months. All-cause and cardiovascular-related mortality were assessed for each group on an adjusted basis (age and sex) and analyzed by cardiac damage stage. Patients with LFLG AS had greater associated cardiac damage at diagnosis (stages 3 and 4 in 34% of those with classical LFLG, 22.5% of those with paradoxical LFLG, 15.5% of those with NFLG, and 14% of those with high-gradient AS; P<.001). For all four major subtypes of severe AS, there was a progressive increase in 1- and 5-year mortality with increasing cardiac damage score. For example, for paradoxical LFLG severe AS, compared with stage 0 patients, adjusted 1-year all-cause mortality was 22% higher in stage 1 patients, 55% higher in stage 2 patients (P=.095), and 155% higher in stage 3 and 4 patients (P<.001). Among patients with classical LFLG severe AS, compared with stage 1 patients, adjusted 1-year all-cause mortality was 55% higher in stage 2 patients (P=.018) and 100% higher in stage 3 and 4 patients (P<.001). Regardless of severe AS subtype, increasing severity denoted by the cardiac damage staging classification is strongly associated with increasing mortality risk.

Prognosis of paradoxical low-flow low-gradient aortic stenosis after transcatheter aortic valve replacement.

In paradoxical low-flow low-gradient severe aortic stenosis (PLFLG AS) patients, stroke volume index (SVI) is reduced despite preserved left ventricular ejection fraction (LVEF). Although reduced SVI is already known as a poor prognostic predictor, the outcomes of PLFLG AS patients after transcatheter aortic valve replacement (TAVR) have not been clearly defined. We retrospectively investigated the post-TAVR outcomes of PLFLG AS patients in comparison with normal-flow high-gradient aortic stenosis (NFHG AS) patients. The current observational study included 245 patients with NFHG AS (mean transaortic pressure gradient ≥40 mmHg and LVEF ≥ 50%) and 48 patients with PLFLG AS (mean transaortic pressure gradient <40 mmHg, LVEF ≥ 50% and SVI < 35 ml/m2). The endpoints were all-cause mortality, hospitalization for valve-related symptoms or worsening congestive heart failure and New York Heart Association functional class III or IV. PLFLG AS patients had a significantly higher proportion with a history of atrial fibrillation/flutter as compared with NFHG AS patients. All-cause mortality of PLFLG AS patients was worse than that of NFHG AS patients (P = 0.047). Hospitalization for valve-related symptoms or worsening congestive heart failure was more frequent in PLFLG AS patients than in NFHG AS patients (P = 0.041). New York Heart Association functional class III-IV after TAVR was more frequently observed in PLFLG AS patients (P = 0.019). The outcomes of PLFLG AS patients were worse than those of NFHG AS patients in this study. Preexisting atrial fibrillation/flutter was frequent in PLFLG AS patients, and may affect their post-TAVR outcomes. Therefore, closer post-TAVR follow-up should be considered for these patients.

In the midst of a dangerous intersection with unclear therapeutic strategies: a challenging case of severe aortic stenosis

BackgroundOne out of seven patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) may be affected by transthyretin cardiac amyloidosis (ATTR-CA), mostly presenting with low-flow low-gradient AS with mildly reduced ejection fraction. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether TAVR may have a prognostic benefit in ATTR-CA patients with symptomatic severe AS remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients.Clinical caseWe present a case of an 87-year old man with low-flow low-gradient severe AS, for whom a diagnosis of ATTR-CA was suspected based on clinical and echocardiographic criteria specific to coexisting AS and ATTR-CA. The diagnosis was eventually confirmed by positive bone tracer scintigraphy imaging. Following in-depth Heart team discussion, integrating frailty and prognostic information from combined cardiomyopathy states, a decision was made to manage the patient’s severe AS conservatively.ConclusionIn the presented case, we deemed the natural history of ATTR-CA amyloidosis to negatively affect both the patient’ prognosis and procedural risk, adversing TAVR indication despite symptomatic severe AS. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if TAVR may have a prognostic benefit in ATTR-CA - and which ATTR-CA - patients.

Clinical and echocardiographic characteristics of severe aortic stenosis patients with inappropriate left ventricular mass

Introduction and objectivesInappropriate left ventricular mass (iLVM) in patients with aortic stenosis (AS) was associated with unfavorable cardiovascular outcome. Our aim was to study the prevalence and characteristics of iLVM in patients with severe AS. MethodsThose patients with severe AS (valve area <1cm2) in our Echocardiography Laboratory between January 2016 and January 2018 were prospectively included. iLVM was diagnosed when the measured left ventricular mass exceeded by 28% the expected value predicted from height, sex and stroke work. Patients with significant left ventricular dysfunction (left ventricular ejection fraction <40%) were excluded. ResultsNinety patients were included (mean age 76±9 years, 55% women), 83% with iLVM. Patients with iLVM had lower indexed aortic valve area (0.39±0.08 vs 0.48±0.06cm2/m2, P<.001), time–velocity integral ratio (0.22±0.04 vs 0.27±0.04; P<.001), indexed stroke volume (39±9 vs 51±13mL/m2, P<.001), higher acceleration time (113±18 vs 88±22ms, P=.001), acceleration time/ejection time ratio (0.37±0.05 vs 0.28±0.07; P<.001) and valvuloarterial impedance (4.8±1.1 vs 4.2±1.0mmHg/mL/m2, P=.04), whilst we did not find differences in mean gradient (48±11 vs 18±12mmHg; P=.96) or peak velocity (4.4±0.5 vs 4.4±0.5m/s; P=.99). Left ventricular ejection fraction, acceleration time to ejection time ratio, indexed systolic volume and valvuloarterial impedance were the only determining variables of iLVM in multivariable analysis. ConclusionsInappropriate left ventricular mass is a frequent finding in patients with severe AS, with echocardiographic characteristics similar to paradoxical low-flow low-gradient severe AS despite normal left ventricular ejection fraction.

DOES LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN DIFFERENTIATE LOW-FLOW, LOW-GRADIENT SEVERE AORTIC STENOSIS PATIENTS IN ADDITION TO CONVENTIONAL CONTRACTILE RESERVE ASSESSMENT?

Patients with left ventricular (LV) dysfunction, low-flow low-gradient severe aortic stenosis represent a population of high risk, particularly when they do not have LV contractile reserve (CR). CR has been described as an increase in stroke volume index (SVi) ≥20% during dobutamine stress

Large-scale assessment of aortic stenosis: facing the next cardiac epidemic?

Aortic stenosis (AS) is the most frequent valvular disease in developed countries. As society grows older, the prevalence of AS increases. However, the real burden, current aetiology, severity distribution, and echocardiographic patterns of AS are not fully clear. The aim of the present study is to provide an accurate overall picture of AS, focusing on its epidemiology, aetiology, and echocardiographic features. A total of 29 502 consecutive echocardiograpies were prospectively included in this multicentre study. The present sample was composed of patients with advanced age (mean 75.2 years) and similar gender distribution. High proportion (7.2%) showed any grade of AS, with important number of patients (2.8%) presenting severe AS, most of them aged 75 years or more. Coexisting valvular disease appeared in almost half of the sample (49.6%), being the most frequently diagnosed aortic regurgitation (AR) (22%) followed by mitral regurgitation (MR) (15.6%). Degenerative aetiology was found in the vast majority (93.4%) of the studies whereas rheumatic is currently infrequent (3.35%). Low flow-low gradient (LFLG) appeared in 24.6% of patients with severe AS. Atrial fibrillation (23.1% vs. 11.6%; P = 0.002), MR (23.3% vs. 15.1%; P = 0.018), and right ventricle dysfunction (13.3% vs. 5.2%; P = 0.003) appeared frequently in LFLG group. Burden of AS is higher than previously assumed. Degenerative aetiology is the main cause of AS. Most of the patients are elder with high prevalence of significant co-existing valvular disease. LFLG severe AS is present in an important proportion of patients, showing high grade of left ventricle remodelling.

Impact of stroke volume assessment by integrating multi-detector computed tomography and Doppler data on the classification of aortic stenosis

BackgroundThe prevalence of low flow low gradient (LFLG) severe aortic stenosis (AS) may be overrated due to underestimation of stroke volume in two-dimensional (2D) echocardiography. The implications of 3D imaging on stroke volume calculation for AS classification have not been elucidated. Integrating multi-detector computed tomography (MDCT) and Doppler data may improve diagnostic accuracy in patients with LFLG AS. MethodsA total of 186 patients with severe AS evaluated for transcatheter aortic valve replacement were classified according to indexed stroke volume (SVI, cut-off 35mL/m2) and mean transaortic pressure gradient (cut-off 40mmHg). SVI was calculated using a) the biplane Simpson's method, b) left ventricular outflow tract (LVOT) velocity time integral (VTI) and LVOT diameter determined by 2D echocardiography, or c) LVOT VTI and LVOT area planimetered by MDCT. ResultsSVI assessed by the biplane Simpson's method was smaller than that obtained from 2D echocardiography LVOT diameter (29.5±0.6 vs 34.9±0.8mL/m2, p<0.001). The latter was smaller than SVI calculated by integrating MDCT and Doppler data (47.5±1.4mL/m2, p<0.001). LFLG and paradoxical LFLG severe AS were diagnosed in 42.5% and 27.4% of patients using the biplane Simpson's method, in 30.1% and 16.7% using 2D echocardiography LVOT diameter, and in 17.2% and 8.1% when integrating MDCT and Doppler data. ConclusionsThe prevalence of LFLG and paradoxical LFLG severe AS was overestimated by 2.5- and 3.4-fold based on 2D echocardiography alone. Integration of MDCT and Doppler data should be considered for stroke volume assessment in the classification of severe AS.

Prognostic Impact of Low-Flow Severe Aortic Stenosis in Small-Body Patients Undergoing TAVR: The OCEAN-TAVI Registry

ObjectivesThis study aimed to analyze the prognostic impact of low-flow (LF) severe aortic stenosis in small-body patients undergoing transcatheter aortic valve replacement (TAVR). BackgroundWestern literature demonstrates a poor prognosis with paradoxical LF and low-flow low-gradient (LF-LG) severe aortic stenosis (AS), as defined by stroke volume index (SVi) <35 ml/m2 and mean pressure gradient <40 mm Hg with preserved left ventricular ejection fraction (LVEF). However, this poor prognosis is contested in Japan owing to the smaller body size of Japanese patients relative to that of Western patients. Additionally, there are no reports of the prognostic implication of paradoxical LF or LF-LG severe AS in small-body patients undergoing TAVR. MethodsThis was a retrospective analysis of 723 consecutive Japanese patients (median age 85 years; 32.6% male; median body surface area 1.4 m2) who underwent TAVR for severe AS at 9 sites in Japan. The primary and secondary endpoints were cumulative all-cause and cardiovascular mortality after TAVR, respectively. ResultsNinety-seven (13.4%) patients had paradoxical LF severe AS whereas 38 (5.3%) had paradoxical LF-LG with severe AS. PLF was associated with a significant increase in all-cause (hazard ratio [HR]: 3.00; 95% confidence interval [CI]: 1.34 to 6.72; p < 0.001) and cardiovascular mortality (HR: 5.58; 95% CI: 1.19 to 26.2; p < 0.01), as compared with patients’ normal flow and preserved LVEF. PLF-LG was associated with a significant increase in all-cause mortality (HR: 3.76; 95% CI: 1.09 to 13.73; p < 0.01), as compared with normal flow high gradient with preserved LVEF. SVi was an independent predictor of cardiovascular mortality on multivariate analysis after adjustments for age, sex, clinically relevant variables, and other echocardiographic parameters (HR: 1.96; 95% CI: 1.19 to 3.23; p < 0.01). ConclusionsAmong Japanese small-body patients with severe AS, both paradoxical LF and LF-LG severe AS were associated with poor outcomes following TAVR. SVi was an independent predictor of cardiovascular mortality after TAVR. (Optimised Transcatheter Valvular Intervention registry [OCEAN-TAVI]; UMIN000020423)

Integration of Flow-Gradient Patterns Into Clinical Decision Making for Patients With Suspected Severe Aortic Stenosis and Preserved LVEF: A Systematic Review of Evidence and Meta-Analysis

ObjectivesThis study was designed to evaluate the evidence base for the 2014 American Heart Association/American College of Cardiology (AHA/ACC) guidelines for severe aortic stenosis (SAS) and preserved left ventricular ejection fraction by comparing the natural history of the disease in subgroups of low-gradient (LG) aortic stenosis patients with high-gradient (HG) patients. BackgroundThe 2014 AHA/ACC valvular disease guidelines recommend estimation of stroke volume index by echocardiography in patients with suspected LG SAS and preserved left ventricular ejection fraction. MethodsPubMed, Embase, and Scopus databases were searched for all studies that have compared the natural history of SAS with preserved ejection fraction in flow-gradient patterns. We studied the following 3 subgroups: HG, low-flow low-gradient (LFLG), and normal-flow low-gradient (NFLG). The random effects model was used to pool individual study results. The end-point was long-term all-cause mortality. ResultsA total of 9 studies with 3,065 patients fulfilled the criteria. Compared to HG SAS, both LFLG and NFLG patients had a higher burden of comorbidities such as coronary artery disease and hypertension. Atrial fibrillation was more prevalent in LFLG patients. Moreover, end-diastolic volume index was smaller for LFLG patients and indexed aortic valve area was larger for NFLG patients. All-cause mortality was similar between HG and LFLG subgroups (relative risk: 1.07; 95% confidence interval: 0.83 to 1.38; p = 0.60), whereas patients with NFLG had a significantly lower all-cause mortality compared to the HG subgroup (relative risk: 0.64; 95% confidence interval: 0.47 to 0.86; p = 0.004). ConclusionsPatients with LFLG SAS have similar outcomes compared to HG SAS but worse compared to NFLG SAS. These findings support estimating stroke volume index in patients with suspected LG SAS. All analyses revealed high heterogeneity and further high-quality studies are necessary.

Low-gradient aortic stenosis.

An important proportion of patients with aortic stenosis (AS) have a 'low-gradient' AS, i.e. a small aortic valve area (AVA <1.0 cm(2)) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS.

Low-flow low-gradient aortic stenosis: surgical outcomes and mid-term results after isolated aortic valve replacement

To analyse operative outcomes and mid-term results following isolated aortic valve replacement (AVR) in patients with low-flow low-gradient severe aortic stenosis (LFLG AS) compared with normal flow high-gradient aortic stenosis (NFHG AS). A retrospective analysis of data for all isolated AVRs performed for AS at our centre in the last 17 years (n = 846). Two groups were identified: LFLG AS (n = 198, 23%) [subdivided into: True LFLG AS (n = 66, 33%) and paradoxical LFLG AS (n = 132, 67%)] and NFHG AS (n = 648, 77%). Follow-up was done by clinical visits and telephone interviews. The mean follow-up was 5.8 ± 4.2 years. The mean age was 71.5 ± 9.7 years in the LFLG AS group and 68.7 ± 10.8 years in the NFHG group (P = 0.01). The LFLG AS group had a mean gradient 31.2 ± 7.4 mmHg compared with 59.1 ± 16.6 mmHg in the NFHG group (P = 0.001). Diabetes, chronic obstructive pulmonary disease, previous coronary disease, peripheral vascular disease, atrial fibrillation and pulmonary hypertension were significantly more frequent in the LFLG AS patients (P < 0.01). The in-hospital mortality rate was 2% in the LFLG and 1% in the NFHG group, P = 0.13. One- and 5-year mortality rates were significantly higher in the LFLG group (13 and 28 vs 4 and 16% in the NFHG, respectively, P = 0.001). Patients with true LFLG AS also had a significantly higher long-term mortality than those with paradoxical LFLG AS (27 vs 6% at 1 year and 42 vs 20% at 5 years, P < 0.05). AVR in patients with LFLG AS is associated with similar surgical mortality but increased mid-term mortality compared with NFHG AS. Patients with true LFLG AS have the worst outcomes. Surgery should still be offered for LFLG AS on prognostic grounds and for symptomatic benefit among survivors.

Dobutamine stress echo for suspected paradoxical low-flow low-gradient severe aortic stenosis: Value of left ventricular wall thickening assessment

Dobutamine stress echo for suspected paradoxical low-flow low-gradient severe aortic stenosis: Value of left ventricular wall thickening assessment