Normal-flow Severe Aortic Stenosis Research Articles

Aortic valve replacement and mortality with left ventricular hypertrophy in setting of normal LVEF

Abstract Background Without symptoms, indications for aortic valve replacement (AVR) in severe aortic stenosis (AS) differ for individuals with normal vs. low/decreasing left ventricular ejection fraction (LVEF). Conceptually, the development of left ventricular hypertrophy (LVH) could also indicate ventricular injury and potential benefit with earlier AVR. However, little is known about the comparative effectiveness of AVR in individuals with LVH. As such, unlike low or dropping LVEF, development of LVH is not in itself an indication for AVR in clinical guidelines. Methods Initially, 1,232,492 echocardiography reports from 12 hospitals were identified from 1 January 2000 to 22 November 2022, and previously validated natural language processing modules were then applied to identify aortic gradients, LVEF, and presence of LVH. These reports were linked to mortality data, key comorbidities with a 2-year lookback covariate window, and date of any AVR. We then isolated echocardiograms demonstrating normal flow severe AS, LVEF ≥ 55% and LVH. Chart reviews were conducted to reduce missing data and outcomes were censored on the date of the chart review (October 4, 2023). To assess the association between AVR and mortality, Cox proportional hazards models considering treatment status (ie, AVR or not) were used with the index echocardiogram as time zero. Covariates used in risk-adjustment were chosen a priori based on conditions and laboratory values used in cardiac surgery mortality risk-adjustment, since those variables could plausibly confound the treatment decision. To address immortal time bias, AVR was considered a time-varying covariate. Multiple additional approaches with propensity scores were performed as sensitivity analyses. Results After application of inclusion and exclusion criteria, 4856 unique patients remained for analysis. Of those, 2043 (42.1%) received AVR with 841/2043 (41.2%) receiving surgical AVR and 1202/2043 (58.8%) receiving transcatheter AVR. Patients who received AVR had lower unadjusted mortality than those who did not receive AVR (33.6% vs. 47.1%, p < 0.001). After adjustment, and accounting for time-dependence of AVR, AVR was associated with reduced mortality (HR 0.81, 95% CI 0.73-0.89, p < 0.0001). The sensitivity analyses were all consistent with the primary analysis. Conclusions AVR was associated with reduced mortality for patients with severe AS, preserved LVEF, and LVH. This association persisted even after accounting for time-dependence, which tends to reduce the observed effectiveness of procedures in observational data. With over a million echocardiograms over more than 20 years, this is the largest known analysis of AVR outcomes in individuals with severe AS and LVH. Our findings suggest LVH may be a high-risk phenotype of individuals with AS, similar to dropping LVEF. As such, these results raise the potential of more proactive AVR clinical guidelines in individuals with LVH, even when LVEF is normal.Survival in AVR Vs No AVR

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.

869 SUCCESSFUL TREATMENT OF COMBINED ANNULAR RUPTURE DURING TRANSCATHETER AORTIC VALVE IMPLANTATION: A CASE REPORT

Abstract Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of patients with severe, symptomatic aortic stenosis. Despite being less invasive than conventional open-chest surgery, TAVI remains associated with rare but serious complications such as vascular injury, stroke, coronary obstruction, cardiac perforation and annular rupture. We report a case of a combined annular rupture successful treated by emergent surgery. Case presentation: A low-risk (EuroSCORE:1.14%) 73-year-old male presenting with high-gradient, normal-flow severe aortic stenosis (AS) was referred to our centre. He had preserved left ventricular ejection fraction and heavily calcified aortic valve. The Heart Team recommended isolated surgical aortic valve replacement, but the patient refused this option. We decided to perform transfemoral-TAVI with a 26 mm Edwards valve which was deployed after predilatation with a 23 mm balloon. Immediately after valve deployment, the angiography revealed contrast leakage at the level of the Valsalva sinuses. The patient developed hypotension due to cardiac tamponade which was immediately managed with pericardial drainage. A bailout cardiac surgery was required to remove the TAVI prosthesis and the native aortic leaflets. A left ventricular outflow tract (LVOT) rupture was observed in addition to supra- annular and intra-annular injury. Repair of the left ventricle with a pericardial patch and implantation of a surgical bioprosthesis (Dafodil Meril 21 mm) were performed. No complications occurred post-operatively Annular rupture occurs in about 1% of all TAVI procedures and may involve the region of the aortic root and LVOT. According to the anatomical location of the injury, it can be classified into 4 types: intra-annular, sub-annular, supra-annular, and combined rupture. Annular rupture has been mainly observed after the use of balloon-expandable valves and only exceptionally after TAVI with self- expandable prosthesis. Nevertheless, the following anatomic characteristics are associated with an increased incidence of this catastrophic event: small aortic valve annulus (&amp;lt;20 mm), a narrow aortic root, heavy calcifications of aortic valve leaflets, annulus, LVOT and sinuses of Valsalva, bicuspid valve, short distance from a coronary artery to the annulus and LV hypertrophy. The voluminous amount of calcification located in the landing zone in addition to the force applied during the balloon expansion may be the main mechanism of this catastrophic complication. Clinical presentation is dramatic and emergent surgery can be the sole solution. Alternative bailout treatments, such as placing a second transcatheter valve to close the rupture have been occasionally reported. A precise preprocedural analysis of the device landing zone is mandatory. This includes determination of the size, morphology of all anatomical structures and a careful identification of possible factors for annular rupture. Moreover, in these cases, the availability of cardiac surgery onsite is pivotal to save patient's life. As more and younger patient will undergo TAVI in next years, our report highlightsthe need to optimize preprocedural planning and prosthesis selection. Improvements in devices, procedural techniques, and imaging tools may simplify TAVI and reduce possible complications.

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.

Clinical and echocardiographic features of paradoxical low-flow and normal-flow severe aortic stenosis patients with concomitant mitral regurgitation.

Mitral regurgitation (MR) coexists in a significant proportion of patients with severe aortic stenosis (AS), and portends inferior therapeutic outcomes. In severe AS, MR is thought to contribute to a low-flow state by decreasing forward stroke volume. We investigated concomitant MR on the clinical and echocardiographic features of patients with "paradoxical" low-flow (PLF) and normal-flow (NF) severe AS. Clinical and echocardiographic profiles of 886 consecutive patients with index echocardiographic diagnosis of severe AS (AVA < 1.0cm2) were analysed retrospectively. All patients had preserved ejection fraction (LVEF ≥50%, n = 645), and were divided into PLF (stroke volume index, SVI < 35mL/m2) and NF AS. They were then further subdivided based on the presence or absence of moderate-or-severe MR (msMR). A higher prevalence of concomitant msMR was observed in patients with PLF AS (14.9%; n = 33/221) compared to those with NF AS (8.0%; n = 34/424). Concomitant msMR was associated with echocardiographic features of increased diastolic dysfunction in both PLF AS and NF AS patients, as evidenced by increased LA diameter (PLF AS 52.9 ± 12.5 to 43.9 ± 8.9mm; NF AS 29.6 ± 10.8 to 42.4 ± 8.8mm; p < 0.001) and increased transmitral E/A ratio (PLF AS 1.26 ± 0.56 to 0.92 ± 0.43; NF AS 1.19 ± 0.63 to 0.94 ± 0.45; p = 0.004). Amongst patients with NF AS, msMR was additionally associated with increased E:e' ratio (25.5 ± 15.1 vs 19.3 ± 10.8; p = 0.025). Concomitant MR was more common in PLF AS compared to NF. Although possibly related to the MR, patients severe AS and MR appeared to have more severe diastolic dysfunction. Further studies are warranted to evaluate prognosis and guide management.

Clinical safety and efficacy of tolvaptan for acute phase therapy in patients with low-flow and normal-flow severe aortic stenosis.

Conventional diuretic therapy for low-flow (LF) severe aortic stenosis (SAS) often has an inadequate effect or causes hemodynamic instability. Tolvaptan is used for acute heart failure in addition to conventional diuretics, and it does not cause intravascular dehydration. This study aimed to retrospectively investigate the safety and efficacy of tolvaptan in the acute phase in 56 consecutive patients with SAS and compared LF-SAS with normal-flow (NF) SAS. The primary endpoints were adverse clinical events (death, worsening heart failure, worsening renal failure, fatal arrhythmia, cardiogenic or hypovolemic shock, and use of inotropic agents) and the volume of urine within 48h of tolvaptan administration. Among 56 patients, 16 had LF-SAS (29%), and 40 had NF-SAS (71%). Severe adverse clinical events were not observed 48h after tolvaptan administration. In both groups, the urine volume significantly increased after tolvaptan administration in comparison to 24h before tolvaptan administration (both, p < 0.01). There were no changes in the urine volume during the initial 24 and 48h. In the LF-SAS group, tolvaptan resulted in a significant decrease in fluid balance during the initial 24 and 48h compared to 24h before tolvaptan administration (p < 0.05). Adding tolvaptan to conventional treatment is safe and effective without renal dysfunction and hypotension in patients with SAS, including those with LF.

Challenges in Aortic Valve Stenosis: Low-Flow States Diagnosis, Management, and a Review of the Current Literature.

We will describe and define the current diagnosis, management, and potential therapy for low-flow aortic stenosis (AS) states, as well as summarize the available evidence underlying these recommendations. Low-flow aortic stenosis syndromes have worse prognoses than traditionally defined normal flow severe aortic stenosis. In this setting, aortic valve replacement is the only therapy that improves outcomes. Transcatheter aortic valve replacement has an ever-expanding role in the treatment of aortic stenosis, and there is growing evidence that TAVR may be a preferred therapy for low-flow AS states. Aortic stenosis remains one of the most common valvular diseases requiring therapy. Low-flow AS represents up to 40% of all patients with AS and is associated with significant mortality. This condition requires further testing for appropriate diagnosis and treatment. Low-flow AS states have poor prognoses, thus AVR and especially TAVR have a growing role in treatment of this challenging subset of AS patients.

Comparing characteristics and clinical and echocardiographic outcomes in low-flow vs normal-flow severe aortic stenosis with preserved ejection fraction in an Asian population.

In severe aortic stenosis (AS), deterioration of left ventricular ejection fraction (LVEF) to <50% is an AHA/ACC class I indication for valve replacement, regardless of symptoms. Controversy surrounds prognosis of low-flow AS compared to normal-flow, and no study has examined LVEF deterioration. We compared factors associated with LVEF deterioration (to <50%) and clinical outcomes. Consecutive subjects with low-flow (stroke volume index <35mL/m2 , n=56) and normal-flow (n=72) severe AS (aortic valve area <1cm2 ) with preserved LVEF (>50%) and with paired echocardiography were studied. Univariate and multivariate analyses identified factors associated with LVEF deterioration. Clinical outcomes were determined on follow-up for more than 5years. Significant LVEF deterioration (to <50%) was seen in 18% of low-flow (initial LVEF 63±8% to 32±9%) and 18% of normal-flow AS (61±7% to 31±12%). Independent factors in low-flow AS were hypertension (OR: 30.7, 95% CI: 2.0-467.6, P=.014) and higher end-systolic wall stress (OR: 1.086, 95% CI: 1.022-1.153, P=.008), compared to normal-flow, which were hypertension (OR: 15.9, 95% CI: 3.1-81.9, P=.001), higher septal E/E' ratio (OR: 1.16, 95% CI: 1.01-1.35, P=.043), lower septal S' velocity (OR: 0.204, 95% CI: 0.061-0.682, P=.010), and higher end-systolic wall stress (OR: 1.051, 95% CI: 1.001-1.104, P=.047). Overall, a third of the cohort experienced MACE, regardless of flow (log-rank 0.048, P=.827). However, aortic valve replacement (AVR) rates were lower in low-flow AS (20% vs 43%, P=.005). Low-flow AS despite normal LVEF appears similar to normal-flow in terms of LVEF deterioration and clinical outcomes in our Asian population. AVR rate was lower even though low-flow may not reflect less severe disease.

Causes of death and predictors of survival after aortic valve replacement in low flow vs. normal flow severe aortic stenosis with preserved ejection fraction.

Reduced stroke volume index (SVI) in patients with severe aortic stenosis (AS) and preserved ejection fraction (EF) is associated with adverse outcomes even after aortic valve replacement (AVR), although specific reasons for impaired survival in this group are unknown. We investigated predictors of post-AVR survival and specific cause of death in patients with AS according to SVI. Among 1120 consecutive patients with severe AS (aortic valve area <1.0 cm(2)) and preserved EF (≥50%) using 2-D and Doppler echocardiography who had AVR, 61 (5%) patients had reduced SVI [<35 mL/m(2) (low flow, LF)] and 1059 (95%) had normal SVI [≥35 mL/m(2) (normal flow, NF)]. Survival post-AVR was lower in patients with LF compared with NF [3-year survival in LF group 76% (95% CI 70-82) vs. 89% (95% CI 88-90%), P = 0.03] primarily due to higher cardiac mortality [3-year event rate 13% (95% CI 8-18%) in LF vs. 5% (95% CI 5-7%) in NF, P = 0.02]. Congestive heart failure (CHF) was the most common cause of cardiac death in the LF group (57% of post-AVR cardiac deaths) and was a more frequent cause of death in LF compared with NF (3-year risk 7 vs. 2%, P = 0.008). Multivariable predictors of post-AVR mortality included age, creatinine, haemoglobin, right ventricular systolic pressure, SVI, and cognitive impairment. Reduced SVI is associated with higher cardiac mortality after AVR. CHF is the predominant cause of cardiac mortality after AVR in patients with LF, suggesting the presence of persistent myocardial impairment in this population.