Low-flow Aortic Stenosis Research Articles

Left Ventricular Remodeling in Patients with Low Flow Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Low-flow (LF) aortic stenosis (AS) is common among the elderly and associated with worse outcomes than AS with normal stroke volume. It is unknown whether left ventricular (LV) remodeling identifies patients with LF AS at higher risk of complications.LV remodeling was evaluated in 463 patients with severe LF AS referred for transcatheter aortic valve replacement (TAVR) and classified as adaptive (normal geometry and concentric remodeling) or maladaptive (concentric and eccentric hypertrophy) using American Society of Echocardiography sex-specific criteria. Of these, the 390 who underwent TAVR were followed for the endpoints of heart failure (HF) hospitalization and all-cause mortality.The mean patients age was 79 (74.5-84) years. LV remodeling was adaptive in 57.4% (62 normal geometry, 162 concentric remodeling) and maladaptive in 42.6% (127 concentric hypertrophy, 39 eccentric hypertrophy). During a median follow-up of 3 years, 45 patients (11.5%) were hospitalized for HF and 73 (18.7%) died. After adjustment for widely used echocardiographic parameters, maladaptive remodeling was independently associated with HF hospitalization and death (adjusted HR 1.75, CI 1.03-3.00). There was no significant difference between men and women in the association of maladaptive LV remodeling with the composite outcome (p=0.40 for men and p=0.06 for women).In conclusion, in patients with LF AS, maladaptive LV remodeling prior to TAVR is independently associated with higher incidences of post-procedural HF rehospitalization and death in both men and women. Assessment of LV remodeling has prognostic value over and above LVEF and may improve risk stratification for patients with LF AS.

Stroke volume index (SVI) predicts all-cause mortality following transcatheter aortic valve replacement (TAVR)

BackgroundLeft ventricular systolic dysfunction in patients with severe aortic stenosis (AS) may result in low transvalvular gradients and underestimation of AS severity. A low-flow state may occur with reduced LVEF. Little is known about the implications of low compared to normal flow in patients with reduced LVEF undergoing transcatheter aortic valve replacement (TAVR). ObjectivesWe compared survival rates with degree of flow across stenosed aortic valves and left ventricular dysfunction. We hypothesized that the stroke volume index (SVI) offers essential information regarding survival following TAVR. MethodsWe retrospectively reviewed patients with LVEF <50 % undergoing TAVR at the Gates Vascular Institute in Buffalo, New York, from 2012 to 2017. We performed Receiver Operator Characteristics to examine the value of SVI in predicting the postoperative outcome of patients. Kaplan-Meier and Cox regression analyses were used to investigate the effect of a low-flow state on five-year survival in patients with systolic dysfunction undergoing TAVR. ResultsFive-year survival following TAVR was decreased in patients with low-flow AS (SVI <35 mL/m2) compared to patients with normal flow. Seventy-four percent (n = 50) of patients with low-flow compared to 43 % (n = 22) of patients with normal flow were deceased five years post-TAVR (p ≤0.001). ROC curve indicated SVI to be a clinical predictor of five year survival (AUC 0.732, 95 % CI: 0.641–0.823, p < 0.001). ConclusionPatients with systolic dysfunction and low transvalvular flow AS had increased mortality five years following TAVR. These findings highlight a better prognosis in patients with normal flow and LV systolic dysfunction. Condensed abstractLow-flow aortic stenosis can occur with reduced left ventricular function. We compared survival rates of patients with known reduced left ventricular function in low-flow and normal flow aortic stenosis. This retrospective single-center study examined mortality rates following transcatheter aortic valve replacement. The mean gradient was not a predictor of mortality. This study shows patients with low-flow aortic stenosis have decreased five-year survival following valve replacement.

Increased left ventricular remodelling index in paradoxical low-flow severe aortic stenosis with preserved left ventricular ejection fraction compared to normal-flow severe aortic stenosis.

Patients with paradoxical low-flow (LF) severe aortic stenosis (AS) despite preserved left ventricular ejection fraction (LVEF) appear distinct from normal-flow (NF) patients, showing worse prognosis, more concentric hypertrophy and smaller left ventricular (LV) cavities. The left ventricular remodelling index (LVRI) has been demonstrated to reliably discriminate between physiologically adapted athlete's heart and pathological LV remodelling. We studied patients with index echocardiographic diagnosis of severe AS (aortic valve area <1 cm2) with preserved LVEF (>50%). The LVRI was determined by the ratio of the LV mass to the end-diastolic volume, as previously reported, and was compared between patients with LF and NF AS. Patients were prospectively followed up for at least 3 years, and clinical outcomes were examined in association with LVRI. Of the 450 patients studied, 112 (24.9%) had LF AS. While there were no significant differences in baseline clinical profile between LF and NF patients, LVRI was significantly higher in the LF group. Patients with high LVRI (>1.56 g/mL) had increased all-cause mortality (log-rank 9.18, P = 0.002) and were more likely to be admitted for cardiac failure (log-rank 7.61, P = 0.006) or undergo aortic valve replacement (log-rank 18.4, P < 0.001). After adjusting for the effect of age, hypertension, aortic valve area and mean pressure gradient on multivariate Cox regression, high LVRI remained independently associated with poor clinical outcomes (hazard ratio 1.64, 95% confidence interval 1.19-2.25, P = 0.002). Pathological LV remodelling (increased LVRI) was more common in patients with LF AS, and increased LVRI independently predicts worse clinical outcomes.

Real world application of left ventricular outflow tract diameter prediction and clinical implications

Abstract Background The Left Ventricular Outflow Tract diameter (LVOTd) measured with transthoracic echocardiogram is crucial for stroke volume, flow and effective orifice area (EOA) assessment in aortic stenosis (AS), but it’s also a source of error. A formula for its prediction has been proposed (Leye’s formula), based on body surface area (BSA). However, it has never been validated externally. Purpose The aim of study is to externally validate the equation by Leye et al. in a retrospective, single-center, large cohort of consecutive non-obese patients with severe symptomatic AS undergoing surgical aortic valve replacement. Methods A population of patients with severe symptomatic AS undergoing surgical aortic valve replacement was analyzed; three different LVOTd values were obtained for each patient: measured-LVOTd (m-LVOTd, from echo database), predicted-LVOTd (p-LVOTd, using Leye’s formula) and surgical-LVOTd (s-LVOTd, obtained by surgical reports). p-LVOTd was used to reevaluate stroke volume and EOA. Results Data from 735 patients were collected; mean age was 75±8 years and 417 patients (57%) were men, mean BMI was 25.6 kg/m2 and mean BSA was 1.8 m2. m-LVOTd was significantly lower than p-LVOTd (20.2±2.4mm and 22.4±1.0mm, respectively; bias 2.1mm; p &amp;lt; 0,001). Moreover the difference between p-LVOTd and s-LVOTd (23.2±1.7mm; bias 0.8 mm) was lower than the difference between m-LVOTd and s-LVOTd (bias 3.0 mm). When the stroke volume index (SVi) was calculated through p-LVOTd, its value increased significantly compared to SVi calculated with m-LVOTd (50.0±10.9 vs 40.9±10.2 mL/m2, p&amp;lt;0.001), leading to a significant decrease in patients classified as low-flow AS, from 216 (29%) to 73 (10%) (p&amp;lt;0.001). EOA calculated with p-LVOTd was significantly wider than that calculated using m-LVOTd, and correlation was weak (0.86±0.22 vs 0.70±0.16 cm2, p&amp;lt;0.001; r=0.599, p&amp;lt;0.001). Using the p-LVOTd instead of m-LVOTd has lead to the reclassification of 188 (26%) patients from EOA≤1 cm2 to EOA&amp;gt;1cm2. Conclusion We found that in non-obese patients with severe AS, LVOTd obtained from the simple formula proposed by Leye et al correlates better with the surgical annulus diameter compared with the echocardiographic measurement of LVOT, and this has relevant consequences on AS assessment.

Prognostic Implication of Pulmonary Hypertension in Low-Flow Low-Gradient Aortic Stenosis After Transcatheter Aortic Valve Replacement

Prognostic implications of pulmonary hypertension (PH) in low-flow low-gradient (LG) aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) remains unexplored. We aimed to investigate the impact of baseline and changes in PH after TAVR. In this single-center retrospective study, we included patients who underwent TAVR for low-flow LG AS. Patients were categorized into 2 groups: baseline pulmonary artery systolic pressure (PASP) <46mm Hg (no-to-mild PH) and PASP ≥46mm Hg (moderate-to-severe PH). On the basis of changes in PASP after TAVR, patients were stratified into increased (ΔPASP ≥+5 mm Hg), no change (-4 to +4 mm Hg), and decreased (≤ -5 mm Hg) groups. Primary end point was a composite of all-cause mortality and heart failure rehospitalization. In total, 210 patients were included, 148 in the no-to-mild PH group and 62 in the moderate-to-severe PH group. Median follow-up was 13.2 months. The moderate-to-severe PH group was at an increased risk of composite end point (adjusted hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.8 to 6.9), all-cause mortality (HR 2.4, 95% CI 1.1 to 5.6), and heart failure rehospitalization (HR 8.3, 95% CI 2.9 to 23.7). There were no differences in clinical outcomes among those with increased (32%), no change (28%), and decreased (39%) PASP after TAVR. In conclusion, moderate-to-severe PH at baseline is an independent predictor of worse clinical outcomes in patients with low-flow LG AS who undergo TAVR, and this cohort of patients do not seem to derive the benefits of postoperative reduction of PASP.

Transcatheter aortic valve replacement outcomes in patients with low-flow very low-gradient aortic stenosis.

In patients with severe aortic stenosis (AS), low-flow low-gradient (LG) is a known predictor of worse outcomes. However, very LG may represent a distinct population with further cardiac dysfunction. It is unknown whether this population benefits from transcatheter aortic valve replacement (TAVR). We aimed to describe the patient characteristics and clinical outcomes of low-flow very LG severe AS. This single-centre study included all patients with low-flow severe AS between 2019 and 2021. Patients were divided into groups with very LG [mean pressure gradient (MPG) ≤ 20 mmHg], LG (20 < MPG < 40 mmHg), and high-gradient (HG) (MPG ≥ 40 mmHg). Composite endpoint of all-cause mortality and heart failure rehospitalization was compared. A total of 662 patients [very LG 130 (20%); LG 339 (51%); HG 193 (29%)] were included. Median follow-up was 12 months. Very LG cohort had a higher prevalence of comorbid conditions with lower left ventricular ejection fraction (45% vs. 57% vs. 60%; P < 0.001). There was a graded increase in the risk of composite endpoint in the lower MPG strata (P < 0.001). Among those who underwent TAVR, very LG was an independent predictor of the composite endpoint (adjusted HR 2.42 [1.29-4.55]). While LG and HG cohorts had decreased risk of composite endpoint after TAVR compared with conservative management, very LG was not associated with risk reduction (adjusted HR 0.69 [0.35-1.34]). Low-flow very LG severe AS represents a distinct population with significant comorbidities and worse outcomes. Further studies are needed to evaluate the short- and long-term benefits of TAVR in this population.

Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement

Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived. To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement. This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021. SAVR or TAVR. All-cause and cardiovascular (CV) mortality after aortic valve intervention. Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume). In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.

The role of TAVR in patients with heart failure: do we have the responses to all questions?

Severe aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries. Heart failure (HF) is a frequent comorbidity of this condition and represents a diagnostic and therapeutic challenge. The spectrum of both conditions has become progressively wider in the last decade; HF has been divided in three groups according to left ventricular ejection fraction (LVEF) and severe AS has been reclassified into four groups according to aortic valve (AV) gradient, AV flow measured by LV stroke index, and LVEF. Although all four AS types may be found in patients with signs and symptoms of HF, low-flow AS with low or normal gradient is the most common type in these patients. Several studies have documented that patients with low-flow severe AS have a higher mortality risk than patients with normal-flow and high-gradient AS not only during the natural progression of the disease, but also after either interventional or surgical AV replacement. Existing data support transcatheter AV replacement (TAVR) in patients with severe AS, irrespective of AV gradient, AV flow, and LVEF. Controversial issues, however, are still present on this topic, which has not been adequately addressed by large studies and trials. This clinical review summarizes the epidemiology of the different HF types in patients with severe AS, as well as the impact of HF and LVEF on clinical outcomes of AS patients either untreated or after AV replacement. In particular, we addressed the influence of AV gradient and AV flow on all-cause and cardiovascular mortality in AS patients after TAVR.

Left Ventricular Mechanics Differ in Subtypes of Aortic Stenosis Following Transcatheter Aortic Valve Replacement.

BackgroundLeft ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). We hypothesized that there would be differences in myocardial mechanics, measured by global longitudinal strain (GLS) recovery in patients with four subtypes of severe AS after transcatheter aortic valve replacement (TAVR), stratified based upon flow and gradient.MethodsWe retrospectively evaluated 204 patients with severe AS who underwent TAVR and were followed post-TAVR at our institution for clinical outcomes. Speckle-tracking transthoracic echocardiography was performed pre- and post-TAVR. Patients were classified as: (1) normal-flow and high-gradient, (2) normal-flow and high-gradient with reduced LV ejection fraction (LVEF), (3) classical low-flow and low-gradient, or (4) paradoxical low-flow and low-gradient.ResultsBoth GLS (−13.9 ± 4.3 to −14.8 ± 4.3, P < 0.0001) and LVEF (55 ± 15 to 57 ± 14%, P = 0.0001) improved immediately post-TAVR. Patients with low-flow AS had similar improvements in LVEF (+2.6 ± 9%) and aortic valve mean gradient (−23.95 ± 8.34 mmHg) as patients with normal-flow AS. GLS was significantly improved in patients with normal-flow (−0.93 ± 3.10, P = 0.0004) compared to low-flow AS. Across all types of AS, improvement in GLS was associated with a survival benefit, with GLS recovery in alive patients (mean GLS improvement of −1.07 ± 3.10, P < 0.0001).ConclusionsLV mechanics are abnormal in all patients with subtypes of severe AS and improve immediately post-TAVR. Recovery of GLS was associated with a survival benefit. Patients with both types of low-flow AS showed significantly improved, but still impaired, GLS post-TAVR, suggesting underlying myopathy that does not correct post-TAVR.

Left ventricular myocardial work in patients with high gradient severe symptomatic aortic stenosis

Abstract Background Left ventricular myocardial work (LVMW) is a novel method to evaluated left ventricular (LV) function using pressure-strain loops. It might correct global longitudinal strain (GLS) for afterload, being eventually useful to assess whether GLS reduction is due to reduced contractility (reflected as reduced myocardial work) or increased afterload (reflected as increased myocardial work). Aim To describe indices of LVMW in a group of patients with severe symptomatic aortic stenosis (AS). Methods We prospectively studied 104 consecutive patients (age: 71 years [IQR 66.5–75.5] years, 51% men) with severe symptomatic high gradient AS: mean transaortic pressure gradient: 56.5mmHg [IQR 46.8–67.8]; aortic valve area: 0.73cm2 [IQR 0.61–0.88]; indexed stroke volume: 47.7±1.3 mL/m2 (11 patients with low-flow AS), preserved LV ejection fraction (EV) (LVEF: 56.0% [51.0–61.3]; GLS: −14.5% [IQR −16.1 to −10.6]), with no previous coronary artery disease and no history of cardiomyopathy. Beyond complete transthoracic echocardiography, all patients underwent cardiac magnetic resonance for LV myocardium tissue characterization. As proposed for AS, LV systolic pressure was corrected adding the mean transaortic pressure gradient to non-invasive systolic blood pressure cuff measurement in the echocardiographic algorithm. Four LVMW indices were collected in 83 patients (patients excluded for atrial fibrillation, left bundle branch block or absence of non-invasive blood pressure registration) and correlated to LV function indexes, LV hypertrophy and remodeling, myocardial tissue characterization, BNP and troponin levels (Pearson or Spearman correlation). These same indexes were compared in patients with LV ejection fraction (EF) below and above 50%, normal and reduced flow and presence of replacement fibrosis. Results Global constructive work (GCW) (2658.6±76.4mmHg%), global myocardial work (GMW) (2218.7±74.9mmHg%) and global wasted work (GWE) (262.0mmHg% [198.8–339.5]) were high above normal with concomitant lower work efficiency (WE) (88.0% [83.2–91.8]. Weak correlations were found between LVMW indexes and parameters describing aortic valve severity, flow and LV function (table). Except for significant differences of LVMI in patients with reduced LV ejection fraction (GCW 2770.3±687.4 vs 2056.0±380.7mmHg%, p=0,014 and GMW 2362.5±657.9 vs 1621.3±319.9, p=0,021 in patients with LV EF&amp;gt;50% vs. LV EF&amp;lt;50%, respectively) work indexes were neither significantly different in low-flow patients nor in those with myocardial late gadolinium enhancement. Conclusions Global constructive and myocardial work are increased in these patients with severe aortic stenosis. This might reflect an increased afterload predominance rather than a LV functional impairment, particularly relevant in this group of patients with exclusive high gradient disease and preserved LVEF. Funding Acknowledgement Type of funding sources: None. Correlations between LVMI – LV function

Prevalence and determinants of right ventricular dysfunction in patients with severe symptomatic high gradient aortic stenosis

Abstract Background Right ventricular (RV) function in aortic stenosis (AS) has been largely neglected. Recently it was demonstrated that right ventricular impairment may be influenced by left ventricular (LV) function and afterload, well before overt pulmonary hypertension development. Aim To describe the prevalence of RV dysfunction in a group of patients with severe symptomatic aortic stenosis (AS) and its relation to LV function parameters and afterload. Methods We prospectively studied 93 consecutive patients (age: 73 years [IQR 68–77] years, 55% women) with pure severe symptomatic high gradient aortic stenosis: mean transaortic pressure gradient: 57.0mmHg [IQR 46.9–71.1]; aortic valve area: 0.72cm2 [IQR 0.61–0.88]; indexed stroke volume: 48.8±1.5 mL/m2 (11 patients with low-flow AS), preserved LV ejection fraction (EV) (LVEF: 56.0% [51.0–61.3]; GLS: −14.5% [IQR −16.1 to −10.6]), with no previous coronary artery disease and no history of cardiomyopathy. Beyond complete transthoracic echocardiography, all patients underwent cardiac magnetic resonance (CMR) for LV myocardium tissue characterization (late gadolinium enhancement and extracellular volume). Normal RV function was defined according to TAPSE ≥17mm, tricuspid annular systolic velocity ≥12cm/s, mean free wall longitudinal strain ≤−20%. Patients were divided into four groups: (0) – all three RV parameters below normal (1.1%), (1) – 1 normal parameter (12.9%), (2) – 2 normal parameters (44.1%), (3) – 3 normal parameters (41.9%). Indexes of LV systolic and diastolic function, CMR derived LV geometric remodeling, hypertrophy and tissue characterization, aortic valve disease severity and afterload were compared across the 4 groups of patients. We tried to identify predictors of RV dysfunction (group 0, 1, 2 vs. group 3) at multivariate regression analysis. Results Left ventricular performance parameters, diastolic and myocardial work indexes were significantly different across the groups (Figure). Neither AV severity indexes nor LV tissue characterization were distinct. At multivariate analysis only global constructive work was an independent predictor of RV dysfunction. Conclusion RV dysfunction is common in this group of patients with severe high gradient aortic stenosis and preserved ejection fraction. RV impairment is significantly related to several LV systolic and diastolic parameters and also to LV afterload, probably accounting for RV-LV interdependence. Funding Acknowledgement Type of funding sources: None.

Influence of Atrial Fibrillation on the Diagnosis of Severe Low-Flow Aortic Stenosis

Low-flow severe aortic stenosis (AS) can be difficult to diagnose, particularly in the setting of atrial fibrillation (AF) in which multiple beats (5

Low Relative Valve Load is Associated With Paradoxical Low-Flow Aortic Stenosis Despite Preserved Left Ventricular Ejection Fraction and Adverse Clinical Outcomes

Paradoxical low-flow (LF) severe aortic stenosis (AS) despite preserved left ventricular (LV) ejection fraction (LVEF) has been shown to be distinct from normal-flow (NF) AS, with a poorer prognosis. Relative valve load (RVL) is a novel echocardiographic haemodynamic index based on the ratio of transaortic mean pressure gradient to the global valvulo-arterial impedance (Zva) in order to estimate the contribution of the valvular afterload to the global LV load. We aimed to determine the usefulness of RVL in LF AS versus NF AS. A total of 450 consecutive patients with medically managed severe AS (aortic valve area <1.0 cm2) with preserved LVEF (>50%) were studied. Patients were divided into LF (stroke volume index <35 mL/m2) or NF, and high RVL or low RVL. Baseline clinical and echocardiographic profiles, as well as clinical outcomes, were compared. There were 149 (33.1%) patients with LF. Despite higher global impedance in LF (Zva 6.3±2.4 vs 3.9±0.9 mmHg/mL/m2; p<0.001) compared with NF, the RVL in LF AS was significantly lower (5.4±2.7 vs 9.8±5.1 mL/m2; p<0.001). On multivariable analysis, low RVL (≤7.51) remained independently associated with poor clinical outcomes on Cox regression (hazard ratio, 1.31; 95% confidence interval, 1.03-1.68), with 53.2% sensitivity and 70.3% specificity. This was comparable to other prognostic indices in AS. Kaplan-Meier curves demonstrated that low RVL was associated with increased mortality. Increased systemic arterial afterload may be important in the pathophysiology of LF AS. Low RVL was an independent predictor of poor clinical outcomes in medically managed severe AS. There may be a greater role in the attenuation of systemic arterial afterload in AS to improve outcomes.

THE IMPACT OF FLOW-IMPROVEMENT AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT ON MORTALITY IN PATIENTS WITH LOW FLOW AND SEVERE AORTIC STENOSIS

THE IMPACT OF FLOW-IMPROVEMENT AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT ON MORTALITY IN PATIENTS WITH LOW FLOW AND SEVERE AORTIC STENOSIS

Interaction of stroke volume and myocardial phenotype in patients with severe aortic stenosis referred for intervention: outcome data from the BSCMR AS700 study

Abstract Funding Acknowledgements Type of funding sources: None. onbehalf The BSCMR Valve Consortium Background Patients with low-flow aortic stenosis (LF-AS) have higher mortality than those with high-flow severe AS. The conventional echocardiographic definition of LF-AS is an indexed stroke volume (SVi) &amp;lt;35ml/m2. Whether this cut-off translates to cardiac magnetic resonance (CMR), and how CMR SVi associates with myocardial remodelling (volume/function/scar) and survival is unclear. Purpose To determine the association between CMR SVi, myocardial remodelling and survival in severe symptomatic AS. Methods In a multi-centre longitudinal outcome study of patients with severe AS listed for either surgical (SAVR) or transcatheter aortic valve intervention (TAVI) at six cardiothoracic centres, survival was assessed and stratified by SVi. Patients underwent preprocedural echocardiography and CMR between January 2003 and May 2015. Standardised core-lab analyses on pre-procedural CMR for biventricular volumes, function and scar quantification were performed. All-cause and cardiovascular mortality were tracked for a minimum of two years after AVR. Results A total of 674 patients with severe AS (age 75 ± 14years; 63% male, aortic valve area 0.4 ± 0.1 cm2/m2) were included. Patients with low SVi by CMR &amp;lt;35ml/m2 were older and had a greater burden of comorbidities (atrial fibrillation [AF], diabetes, high BMI). Independent predictors of SVi were age, AF, increased left atrial volume, aortic valve regurgitant fraction and left ventricular mass (LV) mass index (by CMR). There was no difference in SVi with choice of intervention (TAVI vs SAVR) or presence of late gadolinium enhancement. In multivariate analysis (Table 1), SVi was associated with cardiovascular mortality in the whole cohort (HR 0.97, 95%CI 0.95-0.99, p = 0.02), and all-cause mortality after TAVI (HR 0.97, 95%CI 0.95-0.99, p = 0.006) but not SAVR (p = 0.6). Adjusted mortality hazard increases below 50ml/m2 and plateaus between 35-40ml/m2 (Figure 1A), adjusted for LGE, STS score (Society of Thoracic Surgery score) and wall thickness. Conclusion SVi by CMR is an independent predictor of cardiovascular mortality. Mortality hazard increases progressively below a SVi of 50mL/m2. Abstract Figure 1

Natural History of Asymptomatic Severe Aortic Stenosis and the Association of Early Intervention With Outcomes

Whether intervention should be performed in patients with asymptomatic severe aortic stenosis (AS) remains debated. To meta-analyze the natural history of asymptomatic severe AS and examine the association of early intervention with survival. PubMed, Embase, and Cochrane databases were searched from inception to February 1, 2020. Observational studies of adult patients with asymptomatic severe AS. Two investigators independently extracted study and patient characteristics, follow-up time, events, and prognostic indicators of events. Random-effects models were used to derive pooled estimates. The meta-analysis on natural history was performed on the primary end point of all-cause death occurring during a conservative treatment period, with secondary end points consisting of cardiac death, death due to heart failure, sudden death, development of symptoms, development of an indication for aortic valve intervention, and aortic valve intervention. The primary end point for the meta-analysis of early intervention vs a conservative strategy was all-cause death during long-term follow-up. Finally, meta-analysis was performed on the association of prognostic indicators with the composite of death or aortic valve intervention found in multivariable models. A total of 29 studies with 4075 patients with 11 901 years of follow-up were included. Pooled rates per 100 patients per year were 4.8 (95% CI, 3.6-6.4) for all-cause death, 3.0 (95% CI, 2.2-4.1) for cardiac death, 2.0 (95% CI, 1.3-3.1) for death due to heart failure, 1.1 (95% CI, 0.6-2.1) for sudden death, 18.1 (95% CI, 12.8-25.4) for an indication for aortic valve intervention, 18.5 (95% CI, 13.4-25.5) for development of symptoms, and 19.2 (95% CI, 15.5-23.8) for aortic valve intervention. Early intervention was associated with a significant reduction in long-term mortality (hazard ratio, 0.38; 95% CI, 0.25-0.58). Factors associated with worse prognosis were severity of AS, low-flow AS, left ventricular damage, and atherosclerotic risk factors. Data from observational studies and a recent randomized clinical trial suggest that many patients with asymptomatic severe AS develop an indication for aortic valve intervention, and their deaths are mostly cardiac but not only sudden. Other end points besides sudden death should be considered during the decision to perform early intervention that are associated with improved survival.

Transcatheter Aortic Valve Replacement (TAVR) in Patients with Paradoxical Low-Flow Low-Gradient Aortic Stenosis

ABSTRACT Background Aortic valve replacement is recommended in symptomatic patients with severe aortic stenosis (AS) or asymptomatic with reduced left ventricular ejection fraction (LVEF). The treatment algorithm of patients with paradoxical low-flow (pLF-LG) AS is not well defined. The purpose of this study is to examine the efficacy and outcomes of TAVR in patients with pLF-LG AS at our institution. Methods From 2008 to 2017, we retrospectively analyzed patients who underwent TAVR with an LVEF > 50% and stratified into 4 groups based on gradient and stroke volume index. The groups were normal flow, high gradient (NFHG), normal flow, low gradient (NFLG), low flow, high gradient (LFHG), and paradoxical low flow, low gradient (pLF-LG). Baseline, procedural characteristics, post-procedure, 30-day, and 12-month endpoints were obtained. Our primary endpoints included all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE) at post-procedure, 30 days, and 1 year. Results Groups were NF-HG (n = 145), NF-LG (n = 81), LF-HG (n = 97), and pLF-LG (n = 75). There was an increased prevalence of pacemakers in the pLF-LG group (p = 0.01) and a significant difference in the prevalence of atrial fibrillation (AF) (p = 0.01). No difference in post-procedure, 30-day, and 12-month all-cause mortality and MACCE was noted. All patients demonstrated symptomatic improvement as measured by New York Heart Association (NYHA) class at 30 days and 12 months (p < 0.0001) Conclusion When compared to patients with normal flow and high gradients, patients with pLF-LG treated with TAVR had similar procedural complications and 30-day and 1-year mortality with improvement in symptom profile. Once identified as symptomatic, patients with pLF-LG should undergo valve replacement.

Novel Echocardiography-Derived Left Ventricular Stiffness Index in Low-Flow Versus Normal-Flow Severe Aortic Stenosis with Preserved Left Ventricular Ejection Fraction

Background Paradoxical low-flow (LF) severe aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF) may have poorer prognosis than normal-flow (NF) AS, though its pathophysiology remained unclear. In particular, LV stiffness has not been compared between LF vs NF. We used a novel echocardiography-derived index of LV stiffness to compare between these groups. Consecutive patients with medically-managed isolated severe AS (aortic valve area < 1 cm2) and preserved LVEF (>50%) were studied. Echocardiographic LV stiffness index was measured by a method previously validated against cardiac catheterization. We compared LF (stroke volume index, SVI < 35 ml/m2) and NF severe AS. Of the 352 patients, 121 (34%) were LF. Both LF and NF groups had similar demographics, valve areas and indices. Compared to NF, LF severe AS had higher LV stiffness indices (>0.11 ml−1 OR 3.067, 95% CI 1.825–5.128, p < 0.001). Increased LV stiffness was associated with concentric remodelling and more severe diastolic dysfunction, especially in LF AS. An LV stiffness index of > 0.11 ml−1 was independently associated with increased mortality, after adjusting for age, clinical and echocardiographic parameters (HR 2.283 95% CI 1.318–3.968, p = 0.003). Non-invasive echocardiographic-derived index of LV stiffness may be important in LF AS. Increased LV stiffness was related to LV concentric remodelling and diastolic dysfunction, and associated with poorer clinical outcomes in medically-managed AS.

Right ventricle assessment in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

Limited data are available regarding the evaluation of right ventricular (RV) performance in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). To evaluate the prevalence of RV dysfunction in patients with severe AS undergoing TAVI and long-term changes. Consecutive patients with severe AS undergoing TAVI from January 2016 to July 2017 were included. RV anatomical and functional parameters were analyzed: RV diameters, fractional area change, tricuspid annular plane systolic excursion (TAPSE), S-wave tissue Doppler of the tricuspid annulus (RV-S'TDI), global longitudinal strain (RV-GLS), and free wall strain (RV-FWS). Preprocedure and 1-year echo were analyzed. Final population included 114 patients, mean age 83.63±6.31years, and 38.2% women. The prevalence of abnormal RV function was high, variable depending on the parameter that we analyzed, and it showed a significant reduction 1year after TAVI implantation: 13.9% vs 6.8% (TAPSE<17mm), P=.04; 26.3% vs 20% (fractional area change<35%), P=.048; 41.2% vs 29.2% (RV-S'TDI<9.5cm/s), P=.04; 48.7% vs 39.5% (RV-GLS>[20]), P=.049; and 48.7% vs 28.9% (RV-FWS>[20]), P=.03. Significant differences were noted between patients with low-flow (LF) vs normal-flow (NF) AS in RV dysfunction prevalence as well as in RV function recovery which is less evident in LF compared with NF patients. RV dysfunction is high among symptomatic AS patients undergoing TAVI, with variable prevalence depending on the echocardiographic parameter used.

New Insight in the Assessment of Left Ventricular Function in Paradoxical Low Flow Aortic Stenosis Patients with Normal Left Ventricular Ejection Fraction: A Mini-Review

Paradoxical valvular aortic stenosis (VAS) is a challenging area of clinical cardiology for the practitioners. It involves a small aortic valve area, low flow rate and mean pressure gradient although there is normal left ventricular ejection fraction. The aim of this study was to assess left ventricular (LV) dysfunction in a symptomatic severe aortic valve stenosis which is of crucial importance in identifying patients at risk of heart failure, postoperative complications and increased mortality. There are new insights which are involved in assessment of LV myocardial function including global longitudinal strain (GLS) by two-dimensional speckle tracking echocardiography (2D STE), myocardial performance index (MPI) and maximum rate of LV pressure rise (+dP/dt) during isovolumetric contraction time of the LV. This information can provide both diagnostic and prognostic information in addition to standard echocardiographic and clinical parameters. However, a profound understanding of the complex interaction between loading conditions, chamber geometry and contractility is necessary for the correct interpretation of myocardial deformation in order to draw appropriate conclusions in patients with aortic valve disease. This mini review is related to new and novel insights into the assessment of left ventricular function (LVF) in paradoxical low flow aortic stenosis patients with normal left ventricular ejection fraction (LVEF).