Classical Low-flow Low-gradient Aortic Stenosis Research Articles

Difference in Cardiac Response after Transcatheter Aortic Valve Implantation according to Flow and Gradient Pattern.

In patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS), data on the differences in subsequent cardiac structure and function among stratified groups with flow gradient patterns through the aortic valve are insufficient. In this large multicenter study, 4,523 patients undergoing TAVI for severe AS between 2013 and 2019 were divided into 3 groups according to the following criteria: (1) high-gradient AS (HG-AS) (mean pressure gradient [MPG] ≥40 mmHg), (2) classical low-flow low-gradient AS (cLFLG-AS) (MPG <40 mmHg, left ventricular [LV] ejection fraction [LVEF] <50%), and (3) paradoxical low-flow low-gradient AS (pLFLG-AS) (MPG <40 mmHg, LVEF ≥50% but stroke volume index [SVi] <35 mL/m2). Echocardiography was performed at baseline, post-procedure, and 1 year post-TAVI. 3,697, 507, and 319 patients had HG-AS, cLFLG-AS, and pLFLG-AS, respectively. After adjusting for clinical factors, cLFLG-AS and pLFLG-AS had an approximately 1.5-fold higher 2-year all-cause mortality compared with HG-AS. During 1 year following TAVI, compared with HG-AS, cLFLG-AS showed greater reduction of LV systolic diameter (LVDs) and LV diastolic diameter (LVDd) and greater increase of LVEF (p<0.001 for all), and changes in LV mass index (LVMi) and SVi were comparable (p=0.915 and p=0.821, respectively). However, pLFLG-AS demonstrated less reduction of LVDs and LVDd (p=0.039 and p=0.001, respectively), less improvement of LVEF and LVMi (p=0.045 and p<0.001, respectively), and comparable change in SVi (p=0.364). During 1 year post-TAVI, compared with HG-AS, cLFLG-AS achieves smaller LV diameters, greater increase in LVEF, and comparable regression of LVMi, whereas pLFLG-AS does not.

Sex Differences in Aortic Stenosis: From the Pathophysiology to the Intervention, Current Challenges, and Future Perspectives.

Calcific aortic stenosis (AS) is a major cause of morbidity and mortality in high-income countries. AS presents sex-specific features impacting pathophysiology, outcomes, and management strategies. In women, AS often manifests with a high valvular fibrotic burden, small valvular annuli, concentric left ventricular (LV) remodeling/hypertrophy, and, frequently, supernormal LV ejection fraction coupled with diastolic dysfunction. Paradoxical low-flow low-gradient AS epitomizes these traits, posing significant challenges post-aortic valve replacement due to limited positive remodeling and significant risk of patient-prosthesis mismatch. Conversely, men present more commonly with LV dilatation and dysfunction, indicating the phenotype of classical low-flow low-gradient AS, i.e., with decreased LV ejection fraction. However, these distinctions have not been fully incorporated into guidelines for AS management. The only treatment for AS is aortic valve replacement; women are frequently referred late, leading to increased heart damage caused by AS. Therefore, it is important to reassess surgical planning and timing to minimize irreversible cardiac damage in women. The integrity and the consideration of sex differences in the management of AS is critical. Further research, including sufficient representation of women, is needed to investigate these differences and to develop individualized, sex-specific management strategies.

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

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. 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. 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 &lt;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). 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 impact of cardiac damage staging classification in each aortic stenosis subtype undergoing TAVI.

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

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

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

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

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

Risk prediction in patients with classical low-flow, low-gradient aortic stenosis undergoing surgical intervention.

Classical low-flow, low-gradient aortic stenosis (LFLG-AS) is an advanced stage of aortic stenosis, which has a poor prognosis with medical treatment and a high operative mortality after surgical aortic valve replacement (SAVR). There is currently a paucity of information regarding the current prognosis of classical LFLG-AS patients undergoing SAVR and the lack of a reliable risk assessment tool for this particular subset of AS patients. The present study aims to assess mortality predictors in a population of classical LFLG-AS patients undergoing SAVR. This is a prospective study including 41 consecutive classical LFLG-AS patients (aortic valve area ≤1.0 cm2, mean transaortic gradient <40 mmHg, left ventricular ejection fraction <50%). All patients underwent dobutamine stress echocardiography (DSE), 3D echocardiography, and T1 mapping cardiac magnetic resonance (CMR). Patients with pseudo-severe aortic stenosis were excluded. Patients were divided into groups according to the median value of the mean transaortic gradient (≤25 and >25 mmHg). All-cause, intraprocedural, 30-day, and 1-year mortality rates were evaluated. All of the patients had degenerative aortic stenosis, with a median age of 66 (60-73) years; most of the patients were men (83%). The median EuroSCORE II was 2.19% (1.5%-4.78%), and the median STS was 2.19% (1.6%-3.99%). On DSE, 73.2% had flow reserve (FR), i.e., an increase in stroke volume ≥20% during DSE, with no significant differences between groups. On CMR, late gadolinium enhancement mass was lower in the group with mean transaortic gradient >25 mmHg [2.0 (0.0-8.9) g vs. 8.5 (2.3-15.0) g; p = 0.034), and myocardium extracellular volume (ECV) and indexed ECV were similar between groups. The 30-day and 1-year mortality rates were 14.6% and 43.8%, respectively. The median follow-up was 4.1 (0.3-5.1) years. By multivariate analysis adjusted for FR, only the mean transaortic gradient was an independent predictor of mortality (hazard ratio: 0.923, 95% confidence interval: 0.864-0.986, p = 0.019). A mean transaortic gradient ≤25 mmHg was associated with higher all-cause mortality rates (log-rank p = 0.038), while there was no difference in mortality regarding FR status (log-rank p = 0.114). In patients with classical LFLG-AS undergoing SAVR, the mean transaortic gradient was the only independent mortality predictor in patients with LFLG-AS, especially if ≤25 mmHg. The absence of left ventricular FR had no prognostic impact on long-term outcomes.

Clinical Outcomes in High-Gradient, Classical Low-Flow, Low-Gradient, and Paradoxical Low-Flow, Low-Gradient Aortic Stenosis After Transcatheter Aortic Valve Implantation: A Report From the SwissTAVI Registry.

Background In view of the rising global burden of severe symptomatic aortic stenosis, its early recognition and treatment is key. Although patients with classical low-flow, low-gradient (C-LFLG) aortic stenosis have higher rates of death after transcatheter aortic valve implantation (TAVI) when compared with patients with high-gradient (HG) aortic stenosis, there is conflicting evidence on the death rate in patients with severe paradoxical low-flow, low-gradient (P-LFLG) aortic stenosis. Therefore, we aimed to compare outcomes in real-world patients with severe HG, C-LFLG, and P-LFLG aortic stenosis undergoing TAVI. Methods and Results Clinical outcomes up to 5 years were addressed in the 3 groups of patients enrolled in the prospective, national, multicenter SwissTAVI registry. A total of 8914 patients undergoing TAVI at 15 heart valve centers in Switzerland were analyzed for the purpose of this study. We observed a significant difference in time to death at 1 year after TAVI, with the lowest observed in HG (8.8%) aortic stenosis, followed by P-LFLG (11.5%; hazard ratio [HR], 1.35 [95% CI, 1.16-1.56]; P<0.001) and C-LFLG (19.8%; HR, 1.93 [95% CI, 1.64-2.26]; P<0.001) aortic stenosis. Cardiovascular death showed similar differences between the groups. At 5 years, the all-cause death rate was 44.4% in HG, 52.1% in P-LFLG (HR, 1.35 [95% CI, 1.23-1.48]; P<0.001), and 62.8% in C-LFLG aortic stenosis (HR, 1.7 [95% CI, 1.54-1.88]; P<0.001). Conclusions Up to 5 years after TAVI, patients with P-LFLG have higher death rates than patients with HG aortic stenosis but lower death rates than patients with C-LFLG aortic stenosis.

ABCDEG Stress Echocardiography in Aortic Stenosis.

Rest and stress echocardiography (SE) plays a pivotal role in the evaluation of valvular heart disease. The use of SE is recommended in valvular heart disease when there is a mismatch between resting transthoracic echocardiography findings and symptoms. In aortic stenosis (AS), rest echocardiographic analysis is a stepwise approach that begins with the evaluation of aortic valve morphology and proceeds to the measurement of the transvalvular aortic gradient and aortic valve area (AVA) using continuity equations or planimetry. The presence of the following three criteria suggests severe AS: AVA < 1.0 cm2, a peak velocity > 4.0 m/s, or a mean gradient > 40 mmHg. However, in approximately one in three cases, we can observe a discordant AVA < 1 cm2 with a peak velocity < 4.0 m/s or a mean gradient <40 mmHg. This is due to reduced transvalvular flow associated with LV systolic dysfunction (LVEF < 50%) defined as "classical" low-flow low-gradient (LFLG) AS or normal LVEF "paradoxical" LFLG AS. SE has an established role in evaluating LV contractile reserve (CR) patients with reduced LVEF. In classical LFLG AS, LV CR distinguished pseudo-severe AS from truly severe AS. Some observational data suggest that long-term prognosis in asymptomatic severe AS may not be as favorable as previously thought, offering a window of opportunity for intervention prior to the onset of symptoms. Therefore, guidelines recommend evaluating asymptomatic AS with exercise stress in physically active patients, particularly those younger than 70 years, and symptomatic classical LFLG severe AS with low-dose dobutamine SE. A comprehensive SE assessment includes evaluating valve function (gradients), the global systolic function of the LV, and pulmonary congestion. This assessment integrates considerations of blood pressure response, chronotropic reserve, and symptoms. StressEcho 2030 is a prospective, large-scale study that employs a comprehensive protocol (ABCDEG) to analyze the clinical and echocardiographic phenotypes of AS, capturing various vulnerability sources which support stress echo-driven treatment strategies.

Multimodality imaging methods and systemic biomarkers in classical low-flow low-gradient aortic stenosis: Key findings for risk stratification.

The aim of the present study is to assess multimodality imaging findings according to systemic biomarkers, high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) levels, in low-flow, low-gradient aortic stenosis (LFLG-AS). Elevated levels of BNP and hsTnI have been related with poor prognosis in patients with LFLG-AS. Prospective study with LFLG-AS patients that underwent hsTnI, BNP, coronary angiography, cardiac magnetic resonance (CMR) with T1 mapping, echocardiogram and dobutamine stress echocardiogram. Patients were divided into 3 groups according to BNP and hsTnI levels: Group 1 (n = 17) when BNP and hsTnI levels were below median [BNP < 1.98 fold upper reference limit (URL) and hsTnI < 1.8 fold URL]; Group 2 (n = 14) when BNP or hsTnI were higher than median; and Group 3 (n = 18) when both hsTnI and BNP were higher than median. 49 patients included in 3 groups. Clinical characteristics (including risk scores) were similar among groups. Group 3 patients had lower valvuloarterial impedance (P = 0.03) and lower left ventricular ejection fraction (P = 0.02) by echocardiogram. CMR identified a progressive increase of right and left ventricular chamber from Group 1 to Group 3, and worsening of left ventricular ejection fraction (EF) (40 [31-47] vs. 32 [29-41] vs. 26 [19-33]%; p < 0.01) and right ventricular EF (62 [53-69] vs. 51 [35-63] vs. 30 [24-46]%; p < 0.01). Besides, there was a marked increase in myocardial fibrosis assessed by extracellular volume fraction (ECV) (28.4 [24.8-30.7] vs. 28.2 [26.9-34.5] vs. 31.8 [28.9-35.5]%; p = 0.03) and indexed ECV (iECV) (28.7 [21.2-39.1] vs. 28.8 [25.4-39.9] vs. 44.2 [36.4-51.2] ml/m2, respectively; p < 0.01) from Group 1 to Group 3. Higher levels of BNP and hsTnI in LFLG-AS patients are associated with worse multi-modality evidence of cardiac remodeling and fibrosis.

Utility of Doppler Systolic Timing Intervals in Discriminating “True” Severe from “Pseudo-Severe” Stenosis in Classical Low-Flow Low-Gradient Aortic Stenosis

Utility of Doppler Systolic Timing Intervals in Discriminating “True” Severe from “Pseudo-Severe” Stenosis in Classical Low-Flow Low-Gradient Aortic Stenosis

Comparing Outcomes Between Surgical and Transcatheter Aortic Valve Replacement in Classical Low-Flow Low-Gradient Aortic Stenosis

Patients with classic low-flow low-gradient (cLFLG) aortic stenosis (AS) have a poor prognosis but still benefit from aortic valve replacement. There is a paucity of evidence to guide the choice between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). This study compared procedural and midterm outcomes in patients with cLFLG AS between TAVR and SAVR. Patients with cLFLG AS, defined as an aortic valve area ≤1 cm2, mean gradient <40 mm Hg, and left ventricular ejection fraction <50%, were selected from a single center between 2015 and 2020. Inverse probability weighting and regression were used to adjust for differences in baseline characteristics, the nonrandom assignment of treatment modalities, and procedural differences. The primary end point was all-cause mortality. A total of 322 patients (220 TAVR and 102 SAVR) were included. At a follow-up of 4.4 ± 1.5years, the adjusted hazard ratio (HR) for mortality after inverse probability weighting with SAVR was 0.66, 95% confidence interval (CI) 0.31 to 1.35; p=0.24. Worse renal function at baseline (per 10ml/min/m2 increase HR 0.92, 95% CI 0.84 to 1.00, p=0.04) and multiple valve interventions (HR 5.39, 95% CI 2.62 to 11.12, p <0.001) independently predicted mortality. There was no difference in stroke and permanent pacemaker implantation, but the rates of renal replacement therapy were higher among the SAVR cohort: 13.7% versus 0%; p <0.001. In conclusion, among patients with cLFLG AS, there was no difference in midterm mortality between TAVR and SAVR, supporting the use of either treatment. However, in patients with poor renal function or at risk of renal failure, TAVR may be the preferred option.

The diagnostic role of "acceleration time" measurement in patients with classical low flow low gradient aortic stenosis with reduced left ventricular ejection fraction.

In our study, we aimed to assess the role of acceleration time (AT), ejection time (ET), and AT/ET ratio to distinguish between true and pseudo severe AS in patients with classical low flow-low gradient (LF-LG) aortic stenosis (AS) with reduced left ventricular ejection fraction (LVEF). Sixty-seven classical LF-LG AS with reduced LVEF patients who underwent dobutamine stress echocardiography (DSE) were included in the study. According to DSE results, all patients were divided into two groups; true AS and pseudo severe AS. Aortic valve calcium score was measured in patients with inconclusive DSE results. AT and other ejection dynamics (ET and AT/ET) were calculated by taking baseline echocardiographic records into account for all patients. The predictive power of AT and other ejection dynamics were evaluated to estimate true and pseudo severe AS. According to DSE results, out of 67 patients, 44 (65.7%) was diagnosed as true severe AS. There was a statistically significant relation between baseline AT and true AS [adjusted OR 4.47 (95% CI 1.93-10.4), p = 0.001]. The best cutoff value of AT was measured as 100 msec according to the Youden index. This value had a sensitivity value of 77%, specificity value of 87%, positive predictive value of 92%, and a negative predictive value of 67%. The measurement of AT can predict the DSE outcome and can be used for diagnostic purposes to distinguish between true and pseudo severe AS in classical LF-LG AS patients with reduced LVEF.

Incidence and predictors of transthyretin cardiac amyloidosis in patients with degenerative aortic stenosis

Abstract Background The approval of new therapies for treating transthyretin (TTR) cardiac amyloidosis has led to significant interest in identifying patients at high risk for this disease. Investigators have identified a correlation between severe degenerative aortic stenosis (AS) and TTR cardiac amyloidosis in older patients, with several studies finding up to 20% of patients who undergo transcatheter aortic valve replacement (TAVR) having TTR cardiac amyloidosis. These initial TAVR studies were conducted when TAVR was performed almost exclusively in high surgical risk populations. Therefore, the true incidence of TTR cardiac amyloidosis in an all-comers with severe degenerative AS referred for TAVR is unknown. Purpose To identify the true burden of TTR cardiac amyloidosis in a contemporary population of severe degenerative AS undergoing TAVR screening. Methods All patients ≥70 years with severe native valve degenerative AS seen in a multidisciplinary valve clinic were referred for technetium-99m pyrophosphate cardiac scintigraphy (PYP scan) for evaluation of cardiac amyloidosis. Diagnosis was made via combination of planar grade and heart to contralateral lung ratio, confirmed on single positron emission computed tomography/computed tomography (SPECT/CT). Patients with a positive PYP scan were referred to a heart failure clinic where they underwent testing for AL amyloidosis. Results Over a 10 month period, 247 patients seen in valve clinic underwent a PYP scan. Of this cohort, 203 patients ultimately underwent TAVR, 15 surgical aortic valve replacement, and 2 balloon valvuloplasty with 27 patients having not yet undergone a procedure. The positivity rate was 4% (10/247) with 1 patient having an equivocal result. The patients with a positive PYP scan had higher rate of low-flow low-gradient (LFLG) AS (64% vs 29%, p=0.006) and classical LFLG AS (27% vs 8%, p=0.02). Echocardiographic measures associated with a positive PYP scan include a lower global longitudinal strain (−10.0% vs −16.1%, p=0.008), lower average e' (4.5 vs 6.5, p=0.003), and an increased E/A ratio (1.8 vs 1.1, p=0.018). Conclusions The incidence of TTR amyloidosis in a contemporary, severe AS population ≥70 years undergoing TAVR screening appears much lower than previously described in the literature. Echocardiographic traits may be able to predict which patients with severe AS should undergo evaluation for TTR cardiac amyloidosis. Funding Acknowledgement Type of funding sources: None.

Multimodality imaging and systemic biomarkers in classical low-flow low-gradient aortic stenosis: key findings for cardiac remodeling evaluation

Abstract Background Elevated levels of troponin I (hsTnT) and B-type natriuretic peptide (BNP) have been related with poor prognosis in patients with LFLG-AS. Biomarkers are less expensive, more practical and more accessible than imaging tests, so their use can be an alternative to imaging in the evaluation of patients with LFLG-AS. Purpose The aim of the present study is to assess multimodality imaging findings according to systemic biomarkers (i.e. hsTnT and BNP) in Low-Flow, Low-Gradient Aortic Stenosis (LFLG-AS) and reduced left ventricular ejection fraction (LVEF) patients. Methods Prospective study with LFLG-AS patients (LVEF &amp;lt;50%, aortic valve area ≤1,0 cm2 and mean gradient &amp;lt;40 mmHg) that underwent hsTNnT, BNP, cardiac magnetic resonance (CMR) with T1 mapping and 2 dimensional echocardiogram (2DEcho). All patients also underwent dobutamine stress echocardiogram to define aortic stenosis severity. Patients were divided into 3 groups according to BNP and hsTnT levels: Group 1: BNP and hsTnT levels below median (BNP &amp;lt;395 pg/ml and TnI-Ultra &amp;lt;0.042 ng/ml); Group 2: BNP or hsTnT higher than median; and Group 3: both hsTnT and BNP higher than median. Results 49 patients with LFLG-AS were included (Group 1: 17 patients, Group 2: 14 patients and Group 3: 18 patients). Clinical characteristics (including risk scores) were not able to stratify these groups. Patients with elevation of both biomarkers had lower valvuloarterial impedance (P=0.03), lower LVEF (P=0.02), less moderate/severe mitral (P=0.01) and tricuspid regurgitation (P&amp;lt;0.01) by 2DEcho. CMR identified a progressive increase (from Group 1 to 3) of right and left chamber volumes; reduction in right and left ejection fraction and a marked increase in myocardial fibrosis assessed by extracellular volume (ECV) and indexed extracellular volume (iECV) (Figure 1). Conclusion Higher levels of BNP and hsTnT in LFLG-AS patients were associated with worse multi-modality imaging parameters and can be a surrogate of cardiac remodeling. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): No funding

Predictors of true-severe classical low-flow low-gradient aortic stenosis at resting echocardiography

BackgroundClassical low-flow, low-gradient (LF/LG) aortic stenosis (AS) is subclassified into a true-severe (TS) and a pseudo-severe (PS) subform using low-dose dobutamine stress echocardiography (DSE). In clinical practice a resting peak jet velocity (Vmax) >3.5 m/s or a mean transvalvular gradient (MPG) >35 mmHg suggests the presence of TS classical LF/LG AS, but there is no data to support this. The aim of this study was therefore to investigate whether a resting Vmax >3.5 m/s or MPG >35 mmHg reliably predicted diagnosis of TS classical LF/LG AS. MethodsOne hundred (100) consecutive patients with classical LF/LG AS were prospectively recruited. All patients underwent DSE for subcategorization. The impact of Vmax and MPG for the presence of the TS subform were analyzed. ResultsTS classical LF/LG AS was diagnosed in 72 patients. Resting Vmax and resting MPG predicted true-severity with an ROC-AUC of 0.737 (95%CI: 0.635–0.838; p < 0.001) and 0.725 (95%CI: 0.615–0.834; p < 0.001), respectively. The optimal positive predictive values (PPV) for the diagnosis of TS classical LF/LG AS were obtained with a resting Vmax >3.5 m/s or resting MPG >35 mmHg. In a multivariate logistic regression analysis, Vmax >3.5 m/s was independently associated with a 5.33-fold odds-ratio of TS classical LF/LG AS (OR 5.33; 95%CI: 1.34–21.18, p = 0.018). ConclusionsTS classical LF/LG AS can be reliably predicted by a resting Vmax >3.5 m/s or a resting MPG >35 mmHg. Further imaging for subclassification is not needed in this situation.

Patient survival in severe low-flow, low-gradient aortic stenosis after aortic valve replacement or conservative management.

Background and aimClassical and paradoxical low‐flow, low‐gradient (LFLG) aortic stenosis (AS) are the most challenging subtypes of AS. The current therapeutic options are aortic valve replacement (AVR) and conservative management: AVR promotes long‐term survival but is invasive, while conservative management yields a poor prognosis but is noninvasive since it uses no aortic valve replacement (noAVR). The present meta‐analysis investigated the rate of survival of patients with LFLG AS undergoing either AVR or noAVR interventions.MethodsThe meta‐analysis compared the outcomes of AVR with those of noAVR in terms of patient survival. In both groups, a meta‐regression was conducted to investigate the impact on patient survival of the left ventricular ejection fraction (LVEF), either preserved (paradoxical LFLG AS) or reduced (classical LFLG AS).ResultsThe relative risk of survival between the AVR and noAVR groups was 1.99 [1.40, 2.82] (p = .0001), suggesting that survival tends to be better in AVR patients than in noAVR patients. The meta‐regression revealed that a reduced LVEF may be related to a higher survival in AVR patients when compared to a preserved LVEF (p = .04). Finally, the analysis indicated that LVEF seems not to be prognostic of survival in noAVR patients (p = .18).ConclusionsPatients with LFLG AS have better survival if they undergo AVR. In AVR patients, reduced LVEF rather than preserved LVEF is related to better survival, whereas there seems to be no difference in prognostic value between reduced and preserved LVEF in noAVR patients.

Clinical application of stress echocardiography in valvular heart disease: an expert consensus of the Working Group on Valvular Heart Disease of the Polish Cardiac Society.

Valvular heart diseases (VHDs) constitute an increasing problem both as a consequence of population aging and as the sequelae of other heart diseases. Accurate diagnosis is essential for correct clinical decision‑making; however, in many patients, transthoracic and transesophageal echocardiography is insufficient. Stress echocardiography (SE) proved to be a useful tool allowing for simultaneous assessment of left ventricular contractile reserve and HVD hemodynamics under conditions of physiological or pharmacological stress. It is recommended for assessing the severity of VHD, guiding the choice of treatment, as well as for surgical risk stratification. It can be applied both in asymptomatic patients with severe VHD and in symptomatic individuals with moderate disease. In patients with VHD, SE can be performed either as exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE). The first modality is recommended to unmask symptoms or abnormal blood pressure response in patients with aortic stenosis (AS) who report to be asymptomatic or in those with mitral stenosis with discordance between clinical symptoms and the severity of valve disease on transthoracic echocardiography. In asymptomatic patients with paradoxical low‑flow, low‑gradient (LFLG) AS, ESE can be used to assess the severity of stenosis. On the other hand, low‑dose DSE can be a useful diagnostic tool in classical LFLG AS, providing information on stenosis severity and contractile reserve. Moreover, SE is indicated in patients with prosthetic valve when there is discordance between symptoms and echocardiographic findings. It is also recommended in high‑risk surgical patients with VHD with poor functional capacity and more than 2 clinical risk factors. The present paper discusses in detail the use of SE in VHD.

FLOW RESERVE ASSESSED BY FLOW RATE BUT NOT BY STROKE VOLUME PREDICTS MORTALITY IN LOW-FLOW, LOW-GRADIENT AORTIC STENOSIS

Flow reserve i.e. an increase in stroke volume >20% (Δ20%SV) during dobutamine stress echocardiography (DSE), has been used to predict mortality following surgical aortic valve replacement (AVR) in patients with classical low-flow, low-gradient aortic stenosis (CLF-AS). We hypothesized that mean

Transcatheter Aortic Valve Replacement in Patients With Low-Flow, Low-Gradient Aortic Stenosis: The TOPAS-TAVI Registry

BackgroundFew data exist on patients with low-flow, low-gradient aortic stenosis (LFLG-AS) undergoing transcatheter aortic valve replacement (TAVR). Also, very scarce data exist on the usefulness of dobutamine stress echocardiography (DSE) before TAVR in these patients. ObjectivesThe authors sought to evaluate clinical outcomes and changes in left ventricular ejection fraction (LVEF) following TAVR in patients with classical LFLG-AS. MethodsThis multicenter registry included 287 patients with LFLG-AS undergoing TAVR. DSE was performed before TAVR in 234 patients and the presence of contractile reserve was defined as an increase of ≥20% in stroke volume. Transthoracic echocardiography was repeated at hospital discharge and at 1-year follow-up. Clinical follow-up was obtained at 1 and 12 months, and yearly thereafter. ResultsThe median Society of Thoracic Surgeons score of the study population was 7.7% (interquartile range 5.3% to 12.0%), and the mean LVEF and transvalvular gradient were 30.1 ± 9.7% and 25.4 ± 6.6 mm Hg, respectively. The presence of contractile reserve was observed in 45% of patients at DSE. Mortality rates were 3.8%, 20.1%, and 32.3% at 30 days, 1 year, and 2 years, respectively. On multivariable analysis, chronic obstructive pulmonary disease (p = 0.022) and lower hemoglobin values (p < 0.001) were associated with all-cause mortality. Lower hemoglobin values (p = 0.004) and moderate-to-severe aortic regurgitation post-TAVR (p = 0.018) were predictors of the composite of mortality and rehospitalization due to heart failure. LVEF increased by 8.3% (95% confidence interval: 6% to 11%) at 1-year follow-up, and the lack of prior coronary artery bypass graft (p = 0.004), a lower LVEF at baseline (p < 0.001), and a lower stroke volume index at baseline (p = 0.019) were associated with greater increase in LVEF. The absence of contractile reserve at baseline DSE was not associated with any negative effect on clinical outcomes or LVEF changes at follow-up. ConclusionsTAVR was associated with good periprocedural outcomes in patients with LFLG-AS. However, approximately one-third of LFLG-AS TAVR recipients died at 2-year follow-up, with pulmonary disease, anemia, and residual paravalvular leaks associated with poorer outcomes. LVEF improved following TAVR, but DSE failed to predict clinical outcomes or LVEF changes over time. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS Study]; NCT01835028)