Outcomes From Transcatheter Aortic Valve Replacement in Patients With Low-Flow, Low-Gradient Aortic Stenosis and Left Ventricular Ejection Fraction Less Than 30%: A Substudy From the TOPAS-TAVI Registry.
ABSTRACT: Importance:In low-flow, low-gradient aortic stenosis (LFLG AS), the severity of left ventricular dysfunction remains a key factor in the evaluation of aortic valve replacement. Objective:To evaluate the clinical outcomes and changes in left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) in patients with LFLG AS and severe left ventricular dysfunction. Design, Setting, and Participants:This multicenter registry is a substudy of the True or Pseudo-Severe Aortic Stenosis-TAVI registry that included patients with classic LFLG AS, defined as a mean transvalvular gradient less than 35 mm Hg, an effective orifice area less than 1.0 cm2, and an LVEF of 40% or less. Patients were divided in groups with very low (<30%) LVEF and low (30%-40%) LVEF. Dobutamine stress echocardiography (DSE) was performed before TAVR in a subset with very low LVEF, and presence of contractile reserve was defined as an increase of 20% or more in stroke volume. Clinical outcomes were assessed at 1 and 12 months and yearly thereafter, and echocardiography was performed at 1-year follow-up. Retrospective data were collected from 2007 to 2013 and prospective data from January 2013 to March 2018. Data were analyzed from March to October 2018. Exposures:Transcatheter aortic valve replacement in patients with LFLG AS. Main Outcomes and Measures:Changes in LVEF over time; periprocedural and late mortality. Results:A total of 293 patients were included, including 128 (43.7%) with very low LVEF and 165 with low LVEF (56.3%). Their mean (SD) age was 80 (7) years, and most (214 [73.0%]) were men. The mean (SD) LVEF in the very low LVEF group was 22% (5%), compared with 37% (7%) in the low LVEF group (P?
Project description:BACKGROUND:In patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), studies have suggested that reduced left ventricular (LV) ejection fraction (LVEF) and low aortic valve gradient (AVG) are associated with worse long-term outcomes. Because these conditions commonly coexist, the extent to which they are independently associated with outcomes after TAVR is unknown. OBJECTIVES:The purpose of this study was to evaluate the impact of LVEF and AVG on clinical outcomes after TAVR and to determine whether the effect of AVG on outcomes is modified by LVEF. METHODS:Using data from 11,292 patients who underwent TAVR as part of the Transcatheter Valve Therapies Registry, we examined rates of 1-year mortality and recurrent heart failure in patients with varying levels of LV dysfunction (LVEF <30% vs. 30% to 50% vs. >50%) and AVG (<40 mm Hg vs. ?40 mm Hg). Multivariable models were used to estimate the independent effect of AVG and LVEF on outcomes. RESULTS:During the first year of follow-up after TAVR, patients with LV dysfunction and low AVG had higher rates of death and recurrent heart failure. After adjustment for other clinical factors, only low AVG was associated with higher mortality (hazard ratio: 1.21; 95% confidence interval: 1.11 to 1.32; p < 0.001) and higher rates of heart failure (hazard ratio: 1.52; 95% confidence interval: 1.36 to 1.69; p <0.001), whereas the effect of LVEF was no longer significant. There was no evidence of effect modification between AVG and LVEF with respect to either endpoint. CONCLUSIONS:In this series of real-world patients undergoing TAVR, low AVG, but not LV dysfunction, was associated with higher rates of mortality and recurrent heart failure. Although these findings suggest that AVG should be considered when evaluating the risks and benefits of TAVR for individual patients, neither severe LV dysfunction nor low AVG alone or in combination provide sufficient prognostic discrimination to preclude treatment with TAVR.
Project description:<h4>Objectives</h4>The association between extracellular volume (ECV) measured by computed tomography angiography (CTA) and clinical outcomes was evaluated in low-flow low-gradient (LFLG) aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR).<h4>Background</h4>Patients with LFLG AS comprise a high-risk group with respect to clinical outcomes. Although ECV, a marker of myocardial fibrosis, is traditionally measured with cardiac magnetic resonance, it can also be measured using cardiac CTA. The authors hypothesized that in LFLG AS, increased ECV may be associated with adverse clinical outcomes.<h4>Methods</h4>In 150 LFLG patients with AS who underwent TAVR, ECV was quantified using pre-TAVR CTA. Echocardiographic and clinical information including all-cause death and heart failure rehospitalization (HFH) was obtained from electronic medical records. A Cox proportional hazards model was used to evaluate the association between ECV and death+HFH.<h4>Results</h4>During a median follow-up of 13.9 months (range 0.07 to 28.9 months), there were 31 death+HFH events (21%). Patients who experienced death+HFH had a greater median Society of Thoracic Surgery score (9.9 vs. 4.7; p < 0.01), lower left ventricular ejection fraction (42.3 ± 20.2% vs. 52.7 ± 17.2%; p < 0.01), lower mean transvalvular gradient (24.9 ± 8.9 mm Hg vs. 28.1 ± 7.3 mm Hg; p = 0.04) and increased mean ECV (35.5 ± 9.6% vs. 29.9 ± 8.2%; p < 0.01) compared with patients who did not experience death+HFH. In a multivariable Cox proportional hazards model, increase in ECV was associated with increase in death+HFH, (hazard ratio per 1% increase: 1.04, 95% confidence interval: 1.01 to 1.09; p < 0.01).<h4>Conclusions</h4>In patients with LFLG AS, CTA measured increase in ECV is associated with increased risk of adverse clinical outcomes post-TAVR and may thus serve as a useful noninvasive marker for prognostication.
Project description:An 86-year-old man with unremarkable clinical history complaining of asthenia and dyspnea was diagnosed with low-flow low-gradient aortic stenosis [LFLG-AS; left ventricular ejection fraction (LVEF) 40% and transaortic mean gradient 37 mmHg, increasing to 52% and 55 mmHg after dobutamine infusion]. The patient underwent transcatheter aortic valve implantation (TAVI; Edwards CENTERA™ 29, Irvine, CA, USA). The procedure and the following hospital stay were free from complications, with no changes on electrocardiography (ECG). Six months later, few syncopal episodes occurred. No signs of orthostatic hypotension or neurologic disorders were present. Echocardiography showed normal functioning of the prosthetic valve and recovery of LV systolic function (LVEF 55%). Baseline ECG and 24-h Holter monitoring were unremarkable. An implantable loop recorder (ILR) was implanted to verify the occurrence of paroxysmal conduction disturbances. One month later, during a syncopal episode, ILR interrogation showed a complete atrioventricular (AV) block. Therefore, a dual chamber, single lead pacemaker was implanted. We are providing the first report of complete AV block occurring months after TAVI, possibly because of reverse LV remodeling following TAVI, with ensuing relative oversizing of the prosthetic valve. This possibility should be considered in patients with syncope not otherwise explained, and previous TAVI, especially in cases of LFLG-AS. <<b>Learning objective:</b> Complete atrioventricular block can occur even months after transcatheter aortic valve implantation (TAVI), possibly because of left ventricular reverse remodeling following valve replacement, with ensuing relative valve oversizing. This possibility should be considered in patients with syncope not otherwise explained, and previous TAVI, especially in cases of low flow low gradient aortic stenosis. Loop recorder implantation should be considered in this group of patients.>.
Project description:<h4>Aims</h4>Recovery of left ventricular ejection fraction (LVEF) after aortic valve replacement has prognostic importance in patients with aortic stenosis (AS). The mechanism by which myocardial fibrosis impacts LVEF recovery in AS is not well characterized. We sought to evaluate the predictive value of extracellular volume fraction (ECV) quantified by cardiac CT angiography (CTA) for LVEF recovery in patients with AS after transcatheter aortic valve replacement (TAVR).<h4>Methods and results</h4>In 109 pre-TAVR patients with LVEF <50% at baseline echocardiography, CTA-derived ECV was calculated as the ratio of change in CT attenuation of the myocardium and the left ventricular (LV) blood pool before and after contrast administration. Early LVEF recovery was defined as an absolute increase of ≥10% in LVEF measured by post-TAVR follow-up echocardiography within 6 months of the procedure. Early LVEF recovery was observed in 39 (36%) patients. The absolute increase in LVEF was 17.6 ± 8.8% in the LVEF recovery group and 0.9 ± 5.9% in the no LVEF recovery group (P < 0.001). ECV was significantly lower in patients with LVEF recovery compared with those without LVEF recovery (29.4 ± 6.1% vs. 33.2 ± 7.7%, respectively, P = 0.009). In multivariable analysis, mean pressure gradient across the aortic valve [odds ratio (OR): 1.07, 95% confidence interval (CI): 1.03-1.11, P: 0.001], LV end-diastolic volume (OR: 0.99, 95% CI: 0.98-0.99, P: 0.035), and ECV (OR: 0.92, 95% CI: 0.86-0.99, P: 0.018) were independent predictors of early LVEF recovery.<h4>Conclusion</h4>Increased myocardial ECV on CTA is associated with impaired LVEF recovery post-TAVR in severe AS patients with impaired LV systolic function.
Project description:Low-dose dobutamine stress echocardiography (DSE) is a valuable tool to distinguish true-severe (TS) from pseudo-severe (PS) low gradient aortic valve stenosis (LGAS) in patients with reduced left ventricular ejection fraction (LVEF). However, only scanty studies reported the clinical utility of DSE in differentiating TS-LGAS patients with preserved LVEF. We investigated the clinical utility of DSE in LGAS patients with preserved LVEF and the echocardiographic determinants suggestive of TS-LGAS. 130 consecutive LGAS patients [indexed aortic valve area (AVA) ≤ 0.6cm<sup>2</sup>/m<sup>2</sup> and mean trans-aortic pressure gradient (PG<sub>mean</sub>) < 40mmHg] with preserved (≥ 50%, n = 63) and reduced (< 50%, n = 67) LVEF were included. DSE defined TS-LGAS (projected AVA ≤ 1 cm<sup>2</sup>) in 61.2% patients with reduced LVEF and in 68.3% patients with preserved LVEF. Multivariate logistic regression analysis showed that baseline AVA was an independent determinant of TS-LGAS both in LVEF ≥ 50% (OR 0.45, P = 0.004) and LVEF < 50% groups (OR 0.55, P = 0.005). Reduced septal and lateral mitral annular plane systolic excursion (MAPSE, OR 0.72 and 0.75, P = 0.013 and 0.016) and septal TDI-s´ were significantly associated with TS-LGAS in patients with LVEF ≥ 50%. Higher systolic pulmonary artery pressure (SPAP, OR 1.43, P = 0.045) was associated with TS-LGAS in patients with LVEF < 50%. DSE is useful to define TS-LGAS also in patients with preserved LVEF. Lower baseline AVA values are linked with TS-LGAS in both patients with reduced and preserved LVEF. Reduced MAPSE and septal TDI-s´ are suggestive of TS-LGAS in patients with preserved LVEF, while higher SPAP is associated with TS-LGAS in patients with reduced LVEF.
Project description:<h4>Objective</h4>Patients with low-flow, low-gradient aortic stenosis (LFLG AS) and reduced left ventricular ejection fraction (LVEF) are known to suffer from poor prognosis after transcatheter aortic valve implantation (TAVI). This study aimed to develop a simple score system for risk prediction in this vulnerable subset of patients.<h4>Methods</h4>All patients with LFLG AS with reduced EF and sufficient CT data for aortic valve calcification (AVC) quantification, who underwent TAVI at five German centres, were retrospectively included. The Risk prEdiction in patients with Low Ejection Fraction low gradient aortic stenosis undergoing TAVI (RELiEF TAVI) score was developed based on multivariable Cox regression for all-cause mortality.<h4>Results</h4>Among all included patients (n=718), RELiEF TAVI score variables were defined as independent predictors of mortality: male sex (HR 1.34 (1.06, 1.68), p=0.013), underweight (HR 3.10 (1.50, 6.40), p=0.0022), chronic obstructive pulmonary disease (HR 1.55 (1.21, 1.99), p=0.001), pulmonary hypertension (HR 1.51 (1.17, 1.94), p=0.0015), atrial fibrillation (HR 1.28 (1.03, 1.60), p=0.028), stroke volume index (HR 0.96 (0.95, 0.98), p<0.001), non-transfemoral access (HR 1.36 (1.05, 1.76), p=0.021) and low AVC density (HR 1.44 (1.15, 1.79), p=0.0012). A score system was developed ranging from 0 to 12 points (risk of 1-year mortality: 13%-99%). Kaplan-Meier analysis for low (0-1 points), moderate (2-4 points) and high RELiEF TAVI score (>4 points) demonstrated rates of 18.0%, 29.0% and 46.1% (p<0.001) for all-cause mortality and 23.8%, 35.9% and 53.4% (p<0.001) for the combined endpoint of all-cause mortality or heart failure rehospitalisation after 1 year, respectively.<h4>Conclusions</h4>The RELiEF TAVI score is based on simple clinical, echocardiographic and CT parameters and might serve as a helpful tool for risk prediction in patients with LFLG AS and reduced LVEF scheduled for TAVI.
Project description:<b>Aims: </b>The aim of present study was to examine the preoperative prevalence and distribution of impaired left ventricular global longitudinal strain (LVGLS) in elderly patients with symptomatic aortic stenosis (AS) undergoing transcutaneous aortic valve replacement (TAVR) and to determine the predictive value of LVGLS on survival.<br><br><b>Methods: </b>We included 411 patients with symptomatic severe AS treated with TAVR during a 5-year period, where a baseline echocardiography including LVGLS assessment was available.<br><br><b>Results: </b>Mean age was 80.1?±?7.1 years and aortic valve area (AVA) index 0.4?±?0.1 cm<sup>2</sup>. 78 patients died during a median follow-up of 762 days. Mean left ventricular ejection fraction (LVEF) was 50?±?13% and mean LVGLS was?-?14.0%. LVEF was preserved in 60% of patients, while impaired LVGLS?>?-?18% was seen in 75% of the patients. Previous myocardial infarction, LVEF?<?50%, LVGLS?>?-?14%, low gradient AS (<?4.0 m/s), tricuspid regurgitant gradient?>?30 mmHg were identified as significant univariate predictors of all-cause mortality. On multivariate analysis LVGLS?>?-?14% (HR 1.79 [1.02-3.14], p?=?0.04) was identified as the only independent variable associated with all-cause mortality. Reduced survival was observed with an impaired LVGLS?>?-?14% in the total population (p?<?0.002) but also in patients with high AS gradient with preserved LVEF. LVGLS provided incremental prognostic value with respect to clinical characteristics, AVA and LVEF (?<sup>2</sup> 19.9, p?=?0.006).<br><br><b>Conclusions: </b>In patients with symptomatic AS undergoing TAVR, impaired LVGLS was highly prevalent despite preserved LVEF. LVGLS?>?-?14% was an independent predictor of all-cause mortality, and survival was reduced if LVGLS?>?-?14%.
Project description:BACKGROUND:Transcatheter aortic valve replacement (TAVR) is increasingly used to treat patients with severe aortic stenosis (AS). Cardiovascular magnetic resonance imaging (CMR) provides reliable and reproducible estimates for assessment of cardiac structure and function after TAVR. The goal of this study was to conduct a systematic review and meta-analysis of the literature to assess left ventricular (LV) volumes, mass and function by CMR after TAVR. METHODS:Using Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we searched PubMed and Embase for studies reporting CMR findings before and at least 1?month after TAVR. Main factors of interest were LV end-diastolic volume index (LVEDVi), LV end-systolic volume index (LVESVi), LV mass index (LVMi), and left ventricular ejection fraction (LVEF). Standardized mean differences (SMD) were pooled by random effects meta-analytic techniques. RESULTS:Of 453 screened publications, 10 studies (published between 2012 and 2018) were included. A total of 305 patients completed pre- and post-TAVR follow-up CMR (mean age range 78.6-85.0?years, follow-up range 6-15?months). Random effects analysis showed TAVR resulted in reduced LVEDVi (SMD: -0.25, 95% CI: -?0.43 to -?0.07, P?=?0.006), LVESVi (SMD: -0.24, 95% CI: -?0.44 to -?0.05, P?=?0.01), LVMi (SMD: -0.82, 95% CI: -?1.0 to -?0.63, P?<?0.001) and increased LVEF (SMD: 22, 95% CI: 6 to 38%, P =?0.006). Heterogeneity across studies was low (I2: 0%, Pheterogeneity?>?0.05 for all). The median reduction was 4?ml/m2 (IQR: 3.1 to 8.2) for LVEDVi, 5?ml/m2 (IQR: 3.0 to 6.0) for LVESVi, and 15.1?g/m2 (IQR: 11.8 to 18.3) for LVMi. The median increase for LVEF was 3.4% (IQR 1.0 to 4.6%). CONCLUSIONS:CMR demonstrates reverse LV remodeling occurrs within 6-15?months after TAVR, with reductions in LVEDVi, LVESVi and LVMi, and increased LVEF.
Project description:Moderate aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF) constitute a clinical entity that has been proposed as a therapeutic target for transcatheter aortic valve replacement (TAVR). It is defined by a mean trans-aortic gradient between 20 and 40 mmHg and an aortic valve area between 1.0 and 1.5 cm2 in patients with LVEF < 50%. Retrospective data suggests a prevalence of 0.8% among patients referred for echocardiographic assessment. These patients are younger and show a higher frequency of previous myocardial infarction than those with severe AS randomized to TAVR in recent trials. In two retrospective studies including patients with moderate AS and reduced LVEF, a one-year mortality rate of 9 and 32% was reported, the latter in patients treated with medical therapy only during follow-up. Echocardiographic diagnosis of moderate AS poses challenges as current guidelines are directed to determine severe AS, and different presentations of moderate and mild AS have been generally neglected. Thus, the nomenclature would need to be revised and a description of possible scenarios is provided in this review. Dobutamine stress echocardiography and computed tomography are promising complementary tools. Likewise, a standardized clinical pathway is needed, in which a high level of suspicion and a low threshold for referral to a heart valve center is warranted. The Transcatheter Aortic Valve Replacement to UNload the Left ventricle in patients with Advanced heart failure (TAVR UNLOAD) trial (NCT02661451) is exploring whether TAVR would improve outcomes in patients receiving optimal heart failure therapy.
Project description:Background The prevalence and outcomes of the different subtypes of severe low-gradient aortic stenosis (AS) in routine clinical cardiology practice have not been well characterized. Methods and Results Data were derived from the National Echocardiography Database of Australia. Of 192 060 adults (aged 62.8±17.8 [mean±SD] years) with native aortic valve profiling between 2000 and 2019, 12 013 (6.3%) had severe AS. Of these, 5601 patients (47%) had high-gradient and 6412 patients (53%) had low-gradient severe AS. The stroke volume index was documented in 2741 (42.7%) patients with low gradient; 1750 patients (64%) with low flow, low gradient (LFLG); and 991 patients with normal flow, low gradient. Of the patients with LFLG, 1570 (89.7%) had left ventricular ejection fraction recorded; 959 (61%) had paradoxical LFLG (preserved left ventricular ejection fraction), and 611 (39%) had classical LFLG (reduced left ventricular ejection fraction). All-cause and cardiovascular-related mortality were assessed in the 8162 patients with classifiable severe AS subtype during a mean±SD follow-up of 88±45 months. Actual 1-year and 5-year all-cause mortality rates varied across these groups and were 15.8% and 49.2% among patients with high-gradient severe AS, 11.6% and 53.6% in patients with normal-flow, low-gradient severe AS, 16.9% and 58.8% in patients with paradoxical LFLG severe AS, and 30.5% and 72.9% in patients with classical LFLG severe AS. Compared with patients with high-gradient severe AS, the 5-year age-adjusted and sex-adjusted mortality risk hazard ratios were 0.94 (95% CI, 0.85-1.03) in patients with normal-flow, low-gradient severe AS; 1.01 (95% CI, 0.92-1.12) in patients with paradoxical LFLG severe AS; and 1.65 (95% CI, 1.48-1.84) in patients with classical LFLG severe AS. Conclusions Approximately half of those patients with echocardiographic features of severe AS in routine clinical practice have low-gradient hemodynamics, which is associated with long-term mortality comparable with or worse than high-gradient severe AS. The poorest survival was associated with classical LFLG severe AS.