Prognostic value of extraaortic-valvular cardiac damage in patients with moderate aortic stenosis and reduced left ventricular ejection fraction.

PURPOSE: The extraaortic-valvular cardiac damage (EVCD) Stage has shown potential for risk stratification for patients with aortic stenosis (AS). This study aimed to examine the usefulness of the EVCD Stage in risk stratification of patients with moderate AS and reduced left ventricular ejection fraction (LVEF). METHODS: Clinical data from patients with moderate AS (aortic valve area, .60-.85 cm2/m2; peak aortic valve velocity, 2.0-4.0 m/s) and reduced LVEF (LVEF 20%-50%) were analyzed during 2010-2019. Patients were categorized into three groups: EVCD Stages 1 (LV damage), 2 (left atrium and/or mitral valve damage), and 3/4 (pulmonary artery vasculature and/or tricuspid valve damage or right ventricular damage). The primary endpoint included a composite of cardiac death and heart failure hospitalization, with non-cardiac death as a competing risk. RESULTS: The study included 130 patients (mean age 76.4 ± 6.8 years; 62.3% men). They were categorized into three groups: 26 (20.0%) in EVCD Stage 1, 66 (50.8%) in Stage 2, and 48 (29.2%) in Stage 3/4. The endpoint occurred in 54 (41.5%) patients during a median follow-up of 3.2 years (interquartile range, 1.4-5.1). Multivariate analysis indicated EVCD Stage 3/4 was significantly associated with the endpoint (hazard ratio 2.784; 95% confidence interval 1.197-6.476; P = .017) compared to Stage 1, while Stage 2 did not (hazard ratio 1.340; 95% confidence interval .577-3.115; P = .500). CONCLUSION: The EVCD staging system may aid in the risk stratification of patients with moderate AS and reduced LVEF.

Moderate aortic stenosis: Navigating the uncharted.

Aortic stenosis (AS) stands as the most common valvular heart disease in developed countries and is characterized by progressive narrowing of the aortic valve orifice resulting in elevated transvalvular flow resistance, left ventricular hypertrophy, and progressive increased risk of heart failure and sudden death. This narrative review explores clinical challenges and evolving perspectives in moderate AS, where discrepancies between aortic valve area and pressure gradient measurements may pose diagnostic and therapeutic quandaries. Transthoracic echocardiography is the first-line imaging modality for AS evaluation, yet cases of discordance may require the application of ancillary noninvasive diagnostic modalities. This review underscores the importance of accurate grading of AS severity, especially in low-gradient phenotypes, emphasizing the need for vigilant follow-up. Current clinical guidelines primarily recommend aortic valve replacement for severe AS, potentially overlooking latent risks in moderate disease stages. The noninvasive multimodality imaging approach-including echocardiography, cardiac magnetic resonance, computed tomography, and nuclear techniques-provides unique insights into adaptive and maladaptive cardiac remodeling in AS and offers a promising avenue to deliver precise indications and exact timing for intervention in moderate AS phenotypes and asymptomatic patients, potentially improving long-term outcomes. Nevertheless, what we may have gleaned from a large amount of observational data is still insufficient to build a robust framework for clinical decision-making in moderate AS. Future research will prioritize randomized clinical trials designed to weigh the benefits and risks of preemptive aortic valve replacement in the management of moderate AS, as directed by specific imaging and nonimaging biomarkers.

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

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

On Left Ventricle Stroke Work Efficiency in Children with Moderate Aortic Valve Regurgitation or Moderate Aortic Valve Stenosis.

The optimal timing for management of pediatric patients with moderate aortic valve disease [moderate aortic stenosis (modAS) or moderate aortic regurgitation (modAR)] remains unknown and largely unexplored. Although usually asymptomatic, the risk of increased left ventricular (LV) wall stress, irreversible myocardial fibrosis and sudden death in untreated moderate conditions warrants clearer risk stratification for appropriate timely intervention. In this study, we explore the use of a patient-specific mathematical model to introduce a new evaluative parameter of LV performance in patients with moderate aortic valve disease. Synthetic patient data (N = 520) representing healthy patients, and patients with modAS or modAR were first generated. Then, data from twenty-five pediatric patients were included in this study (healthy = 9; moderate AS = 8; modAR = 8). The effect of modAS or modAR on LV performance was evaluated by LV stroke work (LVSW) efficiency, a new non-invasive parameter. The results demonstrate that healthy patients possess a very high LVSW efficiency (synthetic data: 91 ± 2%, in vivo data: 92 ± 3%). However, modAS patients have a significant reduction in LVSW efficiency (synthetic data: 78 ± 2%, in vivo data: 76 ± 5%, p < 0.05), whereas modAR patients had the lowest LVSW efficiency (synthetic data: 58 ± 3%, in vivo data: 66 ± 7%; p < 0.05). This highlights that patients with moderate aortic valve disease require careful myocardial assessment, regardless of onset of clinical symptoms as their LV performance is significantly reduced. The evaluation of LVSW efficiency offers a promising avenue for future stratification of mixed aortic valve disease for optimal timing of management and intervention.

Usefulness of velocity ratio in patients with moderate aortic stenosis and reduced left ventricular ejection fraction.

Background. Moderate aortic stenosis (AS) increases left ventricular afterload and results in unfavorable outcomes in patients with reduced left ventricular ejection fraction (LVEF). Velocity ratio (VR) may be appropriate for the evaluation of aortic valve (AV) hemodynamics because of the low dependence on flow. Therefore, this study investigated the usefulness of VR on the clinical outcomes of such patients. Method. Clinical data of patients with moderate AS (AV area, 0.60-0.85 cm2/m2; peak AV velocity, 2.0-4.0 m/s) and reduced LVEF (LVEF 20-50%) were analyzed during 2010-2018. VR was calculated as peak left ventricular outflow tract velocity/peak AV velocity. The primary endpoint included all-cause death, heart failure hospitalization, and AV replacement. Results. In total, 104 patients (mean age, 75.9 ± 7.0 years; 62.5% men) were included. LVEF was 39.5% ± 7.8%. The AV area was 0.72 ± 0.08 cm2/m2, peak AV velocity was 2.59 ± 0.40 m/s, and VR was 0.30 ± 0.07. The follow-up period was 1.7 (0.5-3.5) years. Kaplan-Meier estimates for the endpoint were 59.9% at 3 years. Multivariable analysis revealed that VR (hazard ratio, 0.947; 95% confidence interval, 0.905-0.990; p = .018) was significantly related to this endpoint. Patients with a VR <0.25 had significantly higher incidence rates of the endpoint than those with a VR ≥0.25 (85.6% versus 47.8% at 3 years; p < .001). Conclusions. Patients with moderate AS and reduced LVEF have unfavorable clinical outcomes, particularly those with low VR.

Aortic valve surgery and survival in patients with moderate or severe aortic stenosis and left ventricular dysfunction.

AIMS: We aimed to determine the frequency of aortic valve surgery (AVR) with or without coronary artery bypass grafting (CABG), among patients with moderate/severe aortic stenosis (AS) and left ventricular systolic dysfunction (LVSD), and its relationship with survival. METHODS AND RESULTS: The Duke Echocardiographic Database (N = 132 804) was queried for patients with mean gradient ≥25 mmHg and/or peak velocity ≥3 m/s and LVSD (left ventricular ejection fraction ≤50%) from 1 January 1995-28 February 2014. For analyses purposes, AS was defined both by mean gradient and calculated aortic valve area (AVA) criteria. Time-dependent indicators of AVR in multivariable Cox models were used to assess the relationship of AVR and all-cause mortality. A total of 1634 patients had moderate (N = 1090, 67%) or severe (N = 544, 33%) AS by mean gradient criteria. Overall, 287 (26%) patients with moderate AS and 263 (48%) patients with severe AS underwent AVR within 5 years of the qualifying echo. There were 863 (53%) deaths observed up to 5 years following index echo. After multivariable adjustment in an inverse probability weighted regression model, AVR was associated with higher 5-year survival amongst patients with moderate AS and severe AS whether classified by AVA or mean gradient criteria. Over all, AVR ± CABG compared with medical therapy was associated with significantly lower mortality [hazard ratio, HR = 0.49 (0.38, 0.62), P < 0.0001]. Compared with CABG alone, CABG + AVR was associated with better survival [HR = 0.18 (0.12, 0.27), P < 0.0001]. CONCLUSIONS: In patients with moderate/severe AS and LVSD, mortality is substantial and amongst those selected for surgery, AVR with or without CABG is associated with higher survival. Research is required to understand factors contributing to current practice patterns and the possible utility of transcatheter approaches in this high-risk cohort.

Unraveling the Enigma of Moderate Aortic Stenosis: Challenges and Future Prospects.

According to current guidelines, only clinical surveillance is recommended for patients with moderate aortic valve stenosis (AS), while aortic valve replacement may be considered in patients undergoing surgery for other indications. Recent studies have shown that moderate AS is associated with a high risk of adverse cardiovascular events, including death, especially in patients with left ventricular dysfunction. In this context, multimodality imaging can help to improve the accuracy of moderate AS diagnosis and to assess left ventricular remodeling response. This review discusses the natural history of this valve disease and the role of multimodality imaging in the diagnostic process, summarizes current evidence on the medical and non-medical management, and highlights ongoing trials on valve replacement.

Natural history of moderate aortic stenosis and predictors for mortality: Systematic review and meta-analysis.

Although the current guidelines advocate imaging surveillance for moderate aortic stenosis (AS), recent studies suggest a worse prognosis associated with moderate AS than previously reported. Considering the recent paradigm shift in AS management, the risk/benefit profile of aortic valve replacement (AVR) for moderate AS needs to be re-evaluated. Herein, we conducted meta-analyses of natural history and risk predictors in patients with moderate AS. PubMed and EMBASE were searched through May 2022 to identify studies that investigated the natural history of patients with moderate AS. Meta-analyses with random effects model were conducted. Our analysis included 20 observational studies which enrolled a total of 11,114 patients with moderate AS. The rate of all-cause death was 11.0 [95 % confidence interval (CI), 7.6-14.4] per 100 patients per year. Surgical or transcatheter AVR occurred at a rate of 8.5 (95 % CI, 6.2-10.8; I2, 98.9 %) per 100 patients per year. Occurrence of AVR during follow-up [hazard ratio (HR) (95 % CI) = 0.56 (0.42-0.75), p < 0.001] and early AVR for moderate AS [HR (95 % CI) = 0.47 (0.25-0.90), p = 0.02] were associated with significantly lower all-cause mortality, while left ventricular ejection fraction <50 % [HR (95 % CI) = 1.84 (1.33-2.57), p = 0.0003] and symptomatic status [HR (95 % CI) = 1.52 (1.32-1.75), p < 0.0001] were associated with increased all-cause mortality. Sex difference was not related to all-cause mortality. Our meta-analysis suggested that moderate AS was associated with high mortality, especially in low left ventricular systolic function or symptomatic patients. In addition, significant portion of the patients underwent AVR during follow-up.

Aortic valve replacement for moderate aortic stenosis during mitral surgery improves survival free from severe stenosis.

BACKGROUND: Optimal management of moderate aortic stenosis during surgery for another indication is unclear. We assessed the effects of surgical aortic valve replacement for moderate aortic stenosis during mitral surgery. METHODS: An institutional mitral surgery database was queried for patients with preoperative moderate aortic stenosis. Patients were stratified by whether they underwent concomitant surgical aortic valve replacement. Morbidity was analyzed using Student's t tests, Wilcoxon rank sum, chi-squared, and Fisher's exact tests. Survival was analyzed using Kaplan-Meier estimation and Cox regression. RESULTS: Of 85 mitral surgery recipients with moderate aortic stenosis from 2012 to 2019, 62 (73%) underwent concomitant surgical aortic valve replacement. Surgical aortic valve replacement recipients were more likely to have bicuspid (11% vs. 0%, p = 0.019) or rheumatic (18% vs. 0%, p = 0.019) aortic valves, and to undergo mitral repair (32% vs. 9%, p = 0.028). Groups did not differ with respect to mitral etiology, New York Heart Association class, or cardiac intervention history (p > 0.05). Postoperatively, groups had similar stroke and gastrointestinal bleed rates (3% vs. 0% and 2% vs. 0% in the surgical aortic valve replacement vs. no surgical aortic valve replacement group respectively, both p > 0.99). Five-year survival free from severe aortic stenosis was higher in the surgical aortic valve replacement group (66% vs. 17%, p = 0.002). Surgical aortic valve replacement protected against the composite of death and progression to severe aortic stenosis at 5 years (hazard ratio: 0.32, p = 0.003). CONCLUSIONS: Surgical aortic valve replacement for moderate aortic stenosis at time of mitral surgery is a well-tolerated strategy to reduce aortic disease progression.

Prognostic Signals From Moderate Valve Disease in Big Data: An Artefact of Digital Imaging and Communications in Medicine Structured Reporting?

BACKGROUND: Recent studies have identified an association between moderate aortic stenosis (AS) and outcome. We assessed whether Digital Imaging and Communications in Medicine (DICOM) structured reporting (SR), which captures and inserts echocardiographic measurements and text data directly into radiological reports, may lead to misclassifying patients with severe AS as moderate. METHODS: Moderate or severe AS cases were filtered from an echocardiography data set based on aortic valve area (AVA) < 1.5 cm2, indexed AVA (AVAi) ≤ 0.85 cm2/m2, mean pressure gradient ≥ 25 mm Hg, dimensionless severity index (DSI) ≤ 0.5, or peak velocity > 3 m/sec. Data validation was conducted by verification of each parameter. All echocardiographic parameters and definitions of AS were compared pre- and postvalidation by taking differences in measurements. Misclassification rates were assessed by determining the percentage of cases that changed AS severity classification and impact on outcomes. Patients were followed over 4.3 ± 1.5 years. RESULTS: Of 2,595 validated echocardiograms with AS, up to 36% of the echocardiographic parameters for AS criteria had a >10% difference between DICOM-SR and manual validation, the highest with mean pressure gradient (36%) and the lowest with DSI (6.5%). The validation process changed the reported degree of AS in up to 20.6% of echocardiograms with resultant changes in AS severity and its association with mortality or heart failure-related hospitalizations. In contrast to multiple quantitative metrics in DICOM-SR after manual validation, clinicians' evaluation of AS severity was unable to distinguish composite outcomes over 3 years between moderate and severe AS. The risk of composite outcomes was significantly increased when severe AS was evidenced by at least 1 echocardiographic parameter of severe AS (hazard ratio = 1.24; 95% CI, 1.12-1.37; P < .001). The greatest hazard was based on DSI only (hazard ratio = 1.26; 95% CI, 1.10-1.44; P < .001), which was higher after manual validation compared to DICOM-SR. Averaging of repeated echo measures including invalid values contributed the most to erroneous data. CONCLUSIONS: Nonpeak data in DICOM-SR led to incorrect categorization of a high proportion of patients based on AS severity definitions. Standardization of data fields and curation to ensure that only peak values are imported from DICOM-SR data are essential.

Is "moderate" aortic stenosis still the right name? A review of the literature.

Current guidelines recommend aortic valve replacement for symptomatic or selected asymptomatic high-risk patients with severe aortic stenosis. Conversely, a watchful waiting attitude applies to patients with moderate aortic stenosis, regardless of their risk profile and symptoms, until the echocardiographic thresholds of severe aortic stenosis are reached. This strategy is based on data reporting high mortality in untreated severe symptomatic aortic stenosis, whereas moderate aortic stenosis has always been perceived as a non-threatening condition, with a benefit-risk balance against surgery. Meanwhile, numerous studies have reported a worrying event rate in these patients, surgical techniques and outcomes have improved significantly and the use of transcatheter aortic valve replacement has become more widespread and extended to lower-risk patients, leaving this strategy open to question, especially for patients with moderate aortic stenosis and left ventricular dysfunction. In this review, we summarize the current state of knowledge about moderate aortic stenosis progression and prognosis. We also discuss the particular case of moderate aortic stenosis associated with left ventricular dysfunction, and the ongoing trials that that might change our paradigm for the management of this "moderate" valvular heart disease.

Managing Patients With Moderate Aortic Stenosis.

Current guidelines recommend that clinical surveillance for patients with moderate aortic stenosis (AS) and aortic valve replacement (AVR) may be considered if there is an indication for coronary revascularization. Recent observational studies, however, have shown that moderate AS is associated with an increased risk of cardiovascular events and mortality. Whether the increased risk of adverse events is caused by associated comorbidities, or to the underlying moderate AS itself, is incompletely understood. Similarly, which patients with moderate AS need close follow-up or could potentially benefit from early AVR is also unknown. In this review, the authors provide a comprehensive overview of the current published reports on moderate AS. They first provide an algorithm that helps to diagnose moderate AS correctly, especially when discordant grading is observed. Although the traditional focus of AS assessment has been on the valve, it is increasingly acknowledged that AS is not only a disease of the aortic valve but also of the ventricle. The authors therefore discuss how multimodality imaging can help to evaluate the left ventricular remodeling response and improve risk stratification in patients with moderate AS. Finally, they summarize current evidence on the management of moderate AS and highlight ongoing trials on AVR in moderate AS.

Incremental value of left ventricular global longitudinal strain in moderate aortic stenosis and reduced left ventricular ejection fraction.

BACKGROUND: Moderate aortic stenosis (AS) often coexists with left ventricular (LV) systolic dysfunction and may affect survival through afterload mismatch. Because outcomes are ultimately driven by the condition of the LV, accurate assessment of LV performance is crucial to improve risk stratification. This study investigated the prognostic value of LV global longitudinal strain (GLS) in patients with moderate AS and reduced LV systolic dysfunction. METHODS: Patients with moderate AS (aortic valve area 1.0-1.5 cm2) and reduced LV ejection fraction (EF) (<50%) were identified. LVGLS was evaluated with speckle-tracking echocardiography. Patients were divided into 2 groups according to an LVGLS value of 11%, based on spline curve analysis. The primary endpoint was all-cause mortality. RESULTS: A total of 166 patients (mean age 73 ± 11 years, 71% male) were included. The cumulative 1- and 5-year mortality rates were higher in patients with LVGLS <11% (25% and 60%) versus LVGLS ≥11% (10% and 27%) (p < 0.001). On multivariable analysis, LVGLS as a continuous variable (HR 0.753; 95% CI 0.673-0.843; p < 0.001) and as a categorical variable (<11%) (HR 3.028; 95% CI 1.623-5.648; p < 0.001) were independently associated with outcomes, whereas LVEF was not. LVGLS provided additional prognostic information in patients with/without coronary artery disease and with mildly versus severely reduced LVEF. In addition, LVGLS had incremental prognostic value over established risk factors, including LVEF. CONCLUSION: The combination of moderate AS and reduced LV systolic dysfunction is associated with a high mortality risk. LVGLS, but not LVEF, is independently associated with mortality and provides incremental prognostic value over established risk factors in patients with moderate AS and reduced LVEF.

Impact of Moderate Aortic Stenosis on Long-Term Clinical Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: The clinical course of patients with moderate aortic stenosis (AS) remains incompletely defined. OBJECTIVES: This study sought to analyze the clinical course of moderate AS and compare it with other stages of the disease. METHODS: Multiple electronic databases were searched to identify studies on adult moderate AS. Random-effects models were used to derive pooled estimates. The primary endpoint was all-cause death. The secondary endpoints were cardiac death, heart failure, sudden death, and aortic valve replacement. RESULTS: Among a total of 25 studies (12,143 moderate AS patients, 3.7 years of follow-up), pooled rates per 100 person-years were 9.0 (95% CI: 6.9 to 11.7) for all-cause death, 4.9 (95% CI: 3.1 to 7.5) for cardiac death, 3.9 (95% CI: 1.9 to 8.2) for heart failure, 1.1 (95% CI: 0.8 to 1.5) for sudden death, and 7.2 (95% CI: 4.3 to 12.2) for aortic valve replacement. Meta-regression analyses detected that diabetes (P = 0.019), coronary artery disease (P = 0.017), presence of symptoms (P < 0.001), and left ventricle (LV) dysfunction (P = 0.009) were associated with a significant impact on the overall estimate of all-cause death. All-cause mortality was higher in patients with reduced LV ejection fraction (<50%) than with normal LV ejection fraction: 16.5 (95% CI: 5.2 to 52.3) and 4.2 (95% CI: 1.4 to 12.8) per 100 person-years, respectively. Compared with moderate AS, the incidence rate difference of all-cause mortality was -3.9 (95% CI: -6.7 to -1.1) for no or mild AS and +2.2 (95% CI: +0.8 to +3.5) for severe AS patients. CONCLUSIONS: Moderate AS appears to be associated with a mortality risk higher than no or mild AS but lower than severe AS, which increases in specific population subsets. The impact of early intervention in moderate AS patients having high-risk features deserves further investigation.

Sex-Related Differences in Medically Treated Moderate Aortic Stenosis.

Background: Recent data showed poor long-term survival in patients with moderate AS. Although sex differences in left ventricular (LV) remodeling and outcome are well described in severe AS, it has not been evaluated in moderate AS. Methods: In this retrospective, multicenter study, patients with a first diagnosis of moderate AS diagnosed between 2001 and 2019 were identified. Clinical and echocardiographic parameters were recorded at baseline and compared between men and women. Patients were followed up for the primary endpoint of all-cause mortality with censoring at the time of aortic valve replacement. Results: A total of 1895 patients with moderate AS (age 73 ± 10 years, 52% male) were included. Women showed more concentric hypertrophy and had more pronounced LV diastolic dysfunction than men. During a median follow-up of 34 (13-60) months, 682 (36%) deaths occurred. Men showed significantly higher mortality rates at 3- and 5-year follow-up (30% and 48%, respectively) than women (26% and 39%, respectively) (p = 0.011). On multivariable analysis, male sex remained independently associated with mortality (hazard ratio 1.209; 95% CI: 1.024-1.428; p = 0.025). LV remodeling (according to LV mass index) was associated with worse outcomes (hazard ratio 1.003; CI: 1.001-1.005; p = 0.006), but no association was observed between the interaction of LV mass index and sex with outcomes. Conclusions: LV remodeling patterns are different between men and women having moderate AS. Male sex is associated with worse outcomes in patients with medically treated moderate AS. Further studies investigating the management of moderate AS in a sex-specific manner are needed.

Left ventricular remodelling patterns in patients with moderate aortic stenosis.

AIMS: Moderate aortic stenosis (AS) is associated with an increased risk of adverse events. Because outcomes in patients with AS are ultimately driven by the condition of the left ventricle (LV) and not by the valve, assessment of LV remodelling seems important for risk stratification. This study evaluated the association between different LV remodelling patterns and outcomes in patients with moderate AS. METHODS AND RESULTS: Patients with moderate AS (aortic valve area 1.0-1.5 cm2) were identified and stratified into four groups according to the LV remodelling pattern: normal geometry (NG), concentric remodelling (CR), concentric hypertrophy (CH), or eccentric hypertrophy (EH). Clinical outcomes were defined as all-cause mortality and a composite endpoint of all-cause mortality and aortic valve replacement (AVR). Of 1931 patients with moderate AS (age 73 ± 10 years, 52% men), 344 (18%) had NG, 469 (24%) CR, 698 (36%) CH, and 420 (22%) EH. Patients with CH and EH showed higher 3-year mortality rates (28% and 32%, respectively) when compared with patients with NG (19%) (P < 0.001). After multivariable adjustment, CH remained independently associated with mortality (HR 1.258, 95% CI 1.016-1.558; P = 0.035), whereas both CH (HR 1.291, 95% CI 1.088-1.532; P = 0.003) and EH (HR 1.217, 95% CI 1.008-1.470; P = 0.042) were associated with the composite endpoint of death or AVR. CONCLUSION: In patients with moderate AS, those who develop CH already have an increased risk of all-cause mortality. Assessment of the LV remodelling patterns may identify patients at higher risk of adverse events, warranting closer surveillance, and possibly earlier intervention.

Left Ventricular Global Longitudinal Strain in Patients with Moderate Aortic Stenosis.

Moderate aortic stenosis (AS) is associated with an increased risk for adverse events. Although reduced left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe AS, its prognostic value in patients with moderate AS is unknown. The aim of this study was to investigate the prognostic implications of LV GLS in patients with moderate AS. METHODS: LV GLS was evaluated using speckle-tracking echocardiography in patients with moderate AS (aortic valve area 1.0-1.5 cm2) and reported as absolute (i.e., positive) values. Patients were divided into three groups: LV ejection fraction (LVEF) < 50% (group 1), LVEF ≥ 50% but LV GLS < 16% (group 2), and LVEF ≥ 50% and LV GLS ≥ 16% (group 3). The LV GLS value of 16% was based on spline curve analysis. The primary end point was all-cause mortality. RESULTS: A total of 760 patients (mean age, 71 ± 12 years; 61% men) were analyzed. During a median follow-up period of 50 months (interquartile range, 26-94 months), 257 patients (34%) died. Patients with LVEF < 50% and LVEF ≥ 50% but LV GLS < 16% showed significantly higher mortality rates at 1-, 3-, and 5-year follow-up (82%, 71%, and 58%; and 92%, 77%, and 58%, respectively) compared with those with LVEF ≥ 50% and LV GLS ≥ 16% (96%, 91%, and 85%, respectively; P < .001). Long-term outcomes were not different between patients with LVEF < 50% and those with LVEF ≥ 50% but LV GLS < 16% (P = .592). LV GLS discriminated higher risk patients even among those with LVEF ≥ 60% (P < .001) or those who were asymptomatic (P < .001). On multivariable analysis, LVEF < 50% (hazard ratio, 2.384; 95% CI, 1.614-3.522; P < .001) and LVEF ≥ 50% but LV GLS < 16% (hazard ratio, 2.467; 95% CI, 1.802-3.378; P < .001) were independently associated with all-cause mortality. CONCLUSIONS: In patients with moderate AS, reduced LV GLS is associated with an increased risk for all-cause mortality, even if LVEF is still preserved.

Evolving Indications of Transcatheter Aortic Valve Replacement-Where Are We Now, and Where Are We Going.

Indications for transcatheter aortic valve replacement (TAVR) have steadily increased over the last decade since the first trials including inoperable or very high risk patients. Thus, TAVR is now the most common treatment of aortic valve stenosis in elderly patients (vs. surgical aortic valve replacement -SAVR-). In this review, we summarize the current indications of TAVR and explore future directions in which TAVR indications can expand.

Prevalence and Prognostic Implications of Discordant Grading and Flow-Gradient Patterns in Moderate Aortic Stenosis.

BACKGROUND: The prognostic implications of discordant grading in severe aortic stenosis (AS) are well known. However, the prevalence of different flow-gradient patterns and their prognostic implications in moderate AS are unknown. OBJECTIVES: The purpose of this study was to investigate the occurrence and prognostic implications of different flow-gradient patterns in patients with moderate AS. METHODS: Patients with moderate AS (aortic valve area >1.0 and ≤1.5 cm2) were identified and divided in 4 groups based on transvalvular mean gradient (MG), stroke volume index (SVi), and left ventricular ejection fraction (LVEF): concordant moderate AS (MG ≥20 mm Hg) and discordant moderate AS including 3 subgroups: normal-flow, low-gradient moderate AS (MG <20 mm Hg, SVi ≥35 mL/m2, and LVEF ≥50%); "paradoxical" low-flow, low-gradient moderate AS (MG <20 mm Hg, SVi <35 mL/m2, and LVEF ≥50%) and "classical" low-flow, low-gradient moderate AS (MG <20 mm Hg and LVEF <50%). The primary endpoint was all-cause mortality. RESULTS: Of 1,974 patients (age 73 ± 10 years, 51% men) with moderate AS, 788 (40%) had discordant grading, and these patients showed significantly higher mortality rates than patients with concordant moderate AS (P < 0.001). On multivariable analysis, "paradoxical" low-flow, low-gradient (HR: 1.458; 95% CI: 1.072-1.983; P = 0.014) and "classical" low-flow, low-gradient (HR: 1.710; 95% CI: 1.270-2.303; P < 0.001) patterns but not the normal-flow, low-gradient moderate AS pattern were independently associated with all-cause mortality. CONCLUSIONS: Discordant grading is frequently (40%) observed in patients with moderate AS. Low-flow, low-gradient patterns account for an important proportion of the discordant cases and are associated with increased mortality. These findings underline the need for better phenotyping patients with discordant moderate AS.