Mean Aortic Valve Pressure Gradient Research Articles

#1397 Predictive factors for bioprosthetic valve stenosis and prognostic factors for survival following TAVR in hemodialysis patients with severe AS

Abstract Background and Aims Transcatheter aortic valve replacement (TAVR) is a promising option for the treatment of severe aortic valve stenosis (AS) in patients undergoing hemodialysis. Although the incidence of bioprosthetic valve deterioration (SVD) after TAVR has been reported to be lower than after surgical aortic valve replacement (SAVR), hemodialysis itself is still associated with a high risk of SVD. Until now, the factors that determine the prognosis of TAVR in hemodialysis patients were unknown. We previously reported that preoperative hypomagnesemia was correlated with an increase in postoperative mean aortic valve pressure gradient (MPG), an index of bioprosthetic valve stenosis as one of the indicators of SVD, in hemodialysis patients (Ren Fail. 2022 Dec;44(1):1083-1089). However, the study had a limited sample size of 24 cases, which raised concerns about statistical power. Therefore, we re-evaluate predictors of SVD and life expectancy in a larger number of post-TAVR hemodialysis patients. Methods From April 2012 to November 2021, all 100 hemodialysis patients treated with TAVR at Osaka University Hospital were included in the analysis. Pre- and post-operative demographic and laboratory data were analyzed by linear mixed-effects model and cox proportional hazards model. Results During the follow-up period (maximum 7 years), 4 out of 100 patients required re-TAVR (valve-in-valve) due to valve stenosis. The MPG increased over time with the lower preoperative serum Mg concentration (linear mixed-effects mode; +1.40 mmHg/year per 1mg/dl lower in Mg, p=0.006). However, serum calcium, phosphate, and intact PTH levels had no significant effect on the increase in MPG. In addition, a higher preoperative left ventricular ejection fraction (LVEF) was associated with a lower risk of death in a multivariate Cox proportional hazards model (hazard ratio [HR] 0.97 per 1% increase in LVEF; P=0.02). Conclusions Consistent with our previous report, preoperative hypomagnesemia was associated with increased MPG after TAVR. In addition, preoperative low cardiac function (LVEF<40%) may be a risk factor for postoperative mortality in dialysis patients. This was a single-center observational study, and the number of patients was still small, so our data may not be necessarily applicable to every patient. Further research is needed to identify a prognostic predictor of SVD and mortality, that will lead to the prevention of adverse outcomes in hemodialysis patients.

One-year initial efficacy and safety outcomes of the premounted dry-pericardium Vienna self-expandable transcatheter aortic valve system: A first-in-human VIVA feasibility study.

The dry-pericardium Vienna transcatheter aortic valve system is repositionable and retrievable, already premounted on the delivery system, eliminating the need for assembly and crimping of the device before valve implantation. The VIVA first-in-human feasibility study, a prospective, nonrandomized, single-center trial, evaluated the Vienna aortic valve in 10 patients with severe symptomatic aortic stenosis, who were at intermediate or high surgical risk. This study, registered at ClinicalTrials.gov (NCT04861805), focused on the safety, feasibility, clinical and hemodynamic performance of the Vienna system up to 1-year follow-up. The mean patient age was 79 ± 5 years, 60% male. Valve sizes used: 26 mm (10%), 29 mm (30%), 31 mm (60%). Key hemodynamic improvements were significant: mean aortic valve pressure gradient (mmHg) decreased from 48.7 to 8.1, aortic valve area (cm2) increased from 0.75 to 1.91, and maximum jet velocity through the aortic valve (m/s) decreased from 4.41 to 1.95 (p < 0.0001). No moderate/severe paravalvular leakage was observed, and computed tomography scans revealed no evidence of hypo-attenuated leaflet thickening. The study recorded one life-threatening bleeding event, two cases requiring postprocedural pacemaker implantation, and three ischemic events, with only one causing lasting neurological impairment. Importantly, there were no cases of cardiovascular mortality and only one noncardiovascular death, which was confirmed as unrelated to the device. The study indicates the Vienna valve as a potential option for severe symptomatic aortic stenosis, designed to streamline the procedure and potentially lower healthcare costs by reducing resource and equipment needs, also procedural errors. Further research is essential to thoroughly evaluate its safety and efficacy.

Prognostic Relevance of Global Myocardial Work Index in Patients with Moderate Aortic Valve Stenosis.

A reduced global myocardial work index (GWI) ≤ 1951 mmHg% is associated with increased mortality in patients with severe aortic valve stenosis (AS). However, parameters predicting the outcome in patients with moderate AS are limited. Therefore, the aim of this study was to evaluate the prognostic value of the GWI in patients with moderate AS. In this prospective study, 103 patients with moderate AS (mean age 72 ± 10 years; male: 69%) underwent standardized transthoracic echocardiography. The primary endpoint was survival without an aortic valve replacement (AVR). After a median follow-up of 30 ± 5 months, 37 patients (36%) were referred for an AVR. Survival without an AVR was 96% at 12 months and 80% at 30 months (>1951 mmHg%) versus 96% and 68% (≤1951 mmHg%). A GWI ≤ 1951 mmHg% did not predict the need for an AVR (hazard ratio 1.31 (95% CI, 0.63-2.72), p = 0.49). Furthermore, there was no significant correlation between the mean GWI (1644 ± 448 mmHg%) and mean aortic valve pressure gradient (24.2 mmHg ± 6.2, p = 0.615) or effective aortic orifice area (1.24 cm2 ± 0.11, p = 0.678). There was no difference between the AVR and non-AVR groups in the occurrence of clinical symptoms. In contrast to patients with severe AS, a GWI ≤ 1951 mmHg% did not predict the need for an AVR. Further research is needed to improve the risk stratification in patients with moderate AS.

Short- and Long-term Clinical Outcomes of Balloon-expandable Versus Self-expanding Valves in Patients Undergoing Transcatheter Aortic Valve Replacement: A Meta-analysis

Background: Distinct clinical differences exist between balloon-expandable valves (BEVs) and self-expanding valves (SEVs) used in transcatheter aortic valve replacement (TAVR) for aortic stenosis. However, randomised data on comparative outcomes are limited. The aim of this meta-analysis was to analyse the differences in short- and longer-term clinical outcomes between the two valve designs. Methods: A comprehensive literature search for all studies up to and including April 2020 on the clinical outcomes of BEVs versus SEVs was performed. Study outcomes were divided into short term (in-hospital or 30 days), intermediate term (1 year) and long term (3 years). The primary outcome was all-cause mortality. Secondary endpoints were stroke or transient ischaemic attack (TIA), life-threatening or major bleeding, at least moderate paravalvular leak (PVL), permanent pacemaker (PPM) implantation, aortic valve area (AVA) and aortic valve mean pressure gradient (AV MPG). Results: A total of 41 studies (BEV, n=23,892; SEV, n=22,055) were included. At in-hospital/30 days, all-cause mortality favoured BEV (OR 0.85; 95% CI [0.75–0.96]). BEV had lower rates of PVL (OR 0.42; 95% CI [0.35–0.51]) and PPM (OR 0.56; 95% CI [0.44–0.72]), but smaller AVA (mean −0.09 cm2; 95% CI [−0.17, 0.00]) and higher AV MPG (mean 2.54 mmHg; 95% CI [1.84–3.23]). There were no significant differences in the incidence of stroke/TIA or bleeding between the two valve designs. At 1 year a lower PPM implantation rate (OR 0.44; 95% CI [0.37–0.52]), fewer PVLs (OR 0.26; 95% CI [0.09–0.77]), smaller AVA (mean −0.23 cm2; 95% CI [−0.35, −0.10]) and higher AV MPG (mean 6.05 mmHg; 95% CI [1.74–10.36]) were observed with BEV. No significant differences were observed in mortality, stroke/TIA or bleeding. There was no significant difference in mortality at 3 years between the two valve designs. Conclusion: In the short–intermediate term, SEVs had better valve haemodynamics but had higher PVL and PPM implantation rates than BEVs. However, there were no differences in intermediate–long-term mortality, stroke or TIA, or bleeding complications. A better understanding of these differences will enable TAVR operators to tailor their valve choice based on individual patient profile.

Prognostic value of transvalvular flow rate in patients with low-gradient severe aortic stenosis: A dobutamine stress echocardiography study.

There are limited data on the clinical relevance of transvalvular flow rate (Qmean ) at rest (Qrest) and at peak stress (Qstress ) during dobutamine stress echocardiography (DSE) in patients with low-gradient severe aortic stenosis (LG-SAS). We retrospectively analyzed the clinical data of patients with LG-SAS who underwent DSE. LG-SAS was defined as an aortic valve (AV) area index of<.6 cm2 /m2 and a mean AV pressure gradient (AVPG) of<40mm Hg. The primary endpoint included all-cause death and heart failure hospitalization. Of 100 patients (mean age 79.5±7.3 years; men, 45.0%; resting left ventricular ejection fraction [LVEF] 52.1%±15.9%; resting stroke volume index 35.8±7.7mL/m2 ; Qrest 171.8±34.9mL/s), the primary endpoint occurred in 51 patients during a median follow-up of 2.84 (interquartile range 1.01-5.21) years. When the study patients were divided into three subgroups based on Qrest and Qstress , the multivariate analysis showed that Qrest<200mL/s and Qstress ≥200mL/s (hazard ratio 3.844; 95% confidence interval 1.143-12.930; p=.030), as well as Qrest and Qstress<200mL/s (hazard ratio 9.444; 95% confidence interval 2.420-36.850; p=.001), were significantly associated with unfavorable outcomes with Qrest and Qstress ≥200mL/s as a reference after adjusting for resting LVEF, resting mean AVPG, chronic kidney disease, New York Heart Association functional class III/IV, and AV replacement. Flow conditions based on the combination of Qrest and Qstress are helpful for risk stratification in LG-SAS patients.

Aortic Valve Area and Strain Measurements by Cardiac MRI and Transthoracic Echocardiography in Severe Aortic Stenosis with Normal Left Ventricular Function.

Transthoracic echocardiography (TTE) is the recommended imaging technique for the evaluation of patients with aortic stenosis (AS). However, in cases with inconclusive findings, cardiac magnetic resonance (CMR) planimetry is used to grade AS severity. This study aimed to compare the results derived from TTE and CMR in patients with severe AS with normal left ventricular (LV) function. In a prospective study, 20 patients with severe AS were recruited and data derived from TTE and CMR modalities were compared with the archived records of 28 age- and sex-matched healthy controls. The data included aortic valve area (AVA), MRI-derived biventricular global strains, and TTE-derived global longitudinal strain (GLS). SPSS software was used to analyze the data with independent samples t test, intraclass correlation coefficient (ICC), and Pearson correlation. P<0.05 was considered statistically significant. An excellent agreement was found in AVA values derived from CMR and TTE with an average ICC of 0.932 (95% CI=0.829-0.973). There was a significant difference in LV-GLS, LV global radial strain (GRS), right ventricular (RV) GRS, and RV global circumferential strain between the groups. A good correlation was found between CMR- and TTE-derived GLS with an average ICC of 0.721 (95% C=0.255-0.896). The mean aortic valve pressure gradient in TTE had a significant inverse linear correlation with LV-GRS in CMR (r=-0.537). All P values were <0.05. There was a good agreement between AVA and strain values derived from cardiac MRI and TTE. The myocardial strain was impaired in patients with severe AS and normal LV function and correlated with disease severity.

Inhibiting the phosphatase activity of soluble epoxide hydrolase attenuates chronic kidney disease-induced calcific aortic valve disease in rats

Calcific aortic valve disease (CAVD) is the most frequent valvulopathy ultimaltely leading to aortic stenosis, one of the driving causes of an increased morbidity and mortality in aging and in patients with chronic kidney disease (CKD). Up to date, there is no available pharmacological treatment to prevent the development and progression of CAVD. Previous studies suggested that the bifunctional enzyme, soluble epoxide hydrolase (sEH), is involved in the regulation of cardiovascular calcification development. Our study aimed to investigate whether the phosphatase activity of sEH is involved in CAVD. Sprague Dawley sEH-P knocking rats (sEH-P KI) were generated using CRISPR/Cas9 method. Eighteen-week-old WT and sEH-P KI rats underwent subtotal nephrectomy (5/6Nx) to mimic CKD. These animals were afterword fed with a high-phosphate chow diet (1.8% phosphorus). In parallel, sham-operated animals on a standard diet (0.9% total phosphorus) served as controls. Twelve weeks after surgery, renal and cardiac parameters were determined and histological analysis of aortic valves was performed. Twelve weeks after surgery, the development of renal dysfunction in 5/6Nx + phosphate WT rats was shown by the augmentation in plasma creatinine and urea nitrogen concentrations and the decline in estimated glomerular filtration rate compared to sham-operated WT rats. These animals also displayed anemia, polyuria and polydipsia. The genetic inhibition of sEH-P did not allow to prevent these alterations. However, inhibiting sEH-P limited hydroxyapatite crystals deposition in the aortic valve of 5/6Nx + phosphate rats compared to 5/6Nx + phosphate WT rats (Fig. 1B, C), associated with a prevention of the decrease in intercusp distance and of the increase in aortic valve mean pressure gradient and in peak aortic valve velocity (Fig. 1A). In addition, left-ventricular diastolic (E/e′) and systolic dysfunction (fractional shortening) as well as cardiac fibrosis were prevented by sEH-P inhibition. Additional experiments on recombinant human and rat sEH allowed to demonstrate that sEH-P metabolizes pyrophosphate anions (PPi), a potent inhibitor of cardiovascular calcification, and that PPi degradation is efficiently prevented by sEH-P inhibition. Taking altogether, these results demonstrate that inhibition of sEH-P prevents aortic valve calcification and its hemodynamical consequences in the 5/6Nx + phosphate rat model, and may serve as a potential therapeutic strategy for the treatment of CAVD.

Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure

Introduction. This study addressed the hypothesis that subtotal nephrectomy associated with a high-phosphorus diet (5/6Nx + P) in rats represents a suitable animal model to mimic the cardiovascular consequences of chronic kidney disease (CKD) including calcified aortic valve disease (CAVD). Indeed, the latter contributes to the high morbidity and mortality of CKD patients and sorely lacks preclinical models for pathophysiological and pharmacological studies. Methods. Renal and cardiovascular function and structure were compared between sham-operated and 5/6 Nx rats + P 10 to 12 weeks after surgery. Results. As expected, 11 weeks after surgery, 5/6Nx + P rats developed CKD as demonstrated by their increase in plasma creatinine and urea nitrogen and decrease in glomerular filtration rate, estimated by using fluorescein-isothiocyanate-labelled sinistrin, anemia, polyuria, and polydipsia compared to sham-operated animals on a normal-phosphorus diet. At the vascular level, 5/6Nx + P rats had an increase in the calcium content of the aorta; a decrease in mesenteric artery dilatation in response to a stepwise increase in flow, illustrating the vascular dysfunction; and an increase in blood pressure. Moreover, immunohistology showed a marked deposition of hydroxyapatite crystals in the aortic valve of 5/6Nx + P rats. Echocardiography demonstrated that this was associated with a decrease in aortic valve cusp separation and an increase in aortic valve mean pressure gradient and in peak aortic valve velocity. Left-ventricular diastolic and systolic dysfunction as well as fibrosis were also present in 5/6Nx + P rats. Conclusion. This study demonstrates that 5/6Nx + P recapitulates the cardiovascular consequences observed in humans with CKD. In particular, the initiation of CAVD was shown, highlighting the interest of this animal model to study the mechanisms involved in the development of aortic stenosis and test new therapeutic strategies at an early stage of the disease.

Risk factors and clinical effects of subclinical leaflet thrombosis after transcatheter aortic valve replacement.

The number of trans-catheter aortic valve replacement (TAVR) procedure is increasing; However, the incidence of leaflet thrombosis is higher in TAVR than in surgical aortic valve replacement (SAVR). In this study, the risk factors for leaflet thrombosis after TAVR and its effects on hemodynamics and clinical course were investigated. Multidetector computed tomography (MDCT) was performed at 1year after TAVR in 94 patients from January 2015 to October 2020 at Samsung Medical Center in South Korea. Among the 94 patients, subclinical leaflet thrombosis occurred in 20 patients, and risk factors were analyzed. In addition, the difference in aortic valve (AV) hemodynamics between the two groups was examined and clinical outcomes compared. Indexed mean sinus of Valsalva (SOV) diameter, AV calcium volume, and post-procedure effective orifice area (EOA) were predictive of subclinical leaflet thrombosis with the area under the curve (AUC) value of 0.670 (P-value = 0.020), 0.695 (P-value = 0.013), and 0.665 (P-value = 0.031), respectively. In echocardiography performed at the time of follow-up CT, the value of AV max velocity and AV mean pressure gradient were higher in the thrombosis group and the EOA and Doppler velocity index values were lower in the thrombosis group than in the no thrombosis group. Clinical outcome was not significantly different between the two groups (log-rank P-value = 0.26). Larger indexed SOV diameter, higher AV calcium volume, and smaller post-procedure AV EOA were risk factors for subclinical leaflet thrombosis after TAVR. Subclinical leaflet thrombosis has a benign course when properly managed.

Abstract 13612: Using Pre-Operative Cardiac Computed Tomography and Echocardiography to Predict New-Onset Atrial Fibrillation Following TAVR

Introduction: New-onset atrial fibrillation (NOAF) following transcatheter aortic valve replacement (TAVR) has been associated with higher morbidity and mortality. Numerous studies have focused on clinical variables for NOAF prediction. In this study, we examine pre-operative cardiac computed tomography (cCT) and echocardiographic measurements for NOAF prediction following TAVR. Methods: This retrospective study includes 939 patients without pre-existing atrial fibrillation who underwent transfemoral TAVR between 2015 and 2020. Clinical data and standard pre-operative echocardiographic and cCT measurements were recorded. A machine learning method was used to derive left atrial volume and measures of epicardial adipose tissue from cCT. NOAF by 30-days was determined based on continuous electrocardiographic monitoring prior to hospital discharge and routine ECG at 2 and 4 weeks following TAVR. In a two-step analysis, random survival forest (RSF) was used to select variables of highest importance to NOAF prediction without assuming statistical models, followed by logistic regression analysis of the selected variables. Results: Among 939 patients, 47 (5%) experienced NOAF. Patients with NOAF had larger left atrial volume index (68.11 vs 56.96 cm 3 /kg/m 2 ; p&lt;0.001) but similar epicardial adipose tissue volume (71.78 vs 70.98 cm 3 ; p&gt;0.1) and epicardial adipose tissue attenuation (-81.16 vs -82.77 Hounsfield Units; p&gt;0.1). Among 28 covariates selected by RSF for variable importance, 4 covariates were predictive of NOAF in the multivariable logistic regression, including sinotubular junction short axis &gt;34mm [OR 5.687 (2.271-14.241); p=0.0002], maximum aortic valve pressure gradient [OR 1.037 (1.004-1.072); p=0.0266], mean aortic valve pressure gradient [OR 0.939 (0.894-0.986); p=0.0115], and body mass index &lt; 22kg/m 2 [OR 0.331 (0.150-0.729); p=0.006]. Model concordance was 0.75. Conclusions: Pre-operative cardiac computed tomography and echocardiographic measurements including sinotubular junction enlargement and aortic valve pressure gradient predict new-onset atrial fibrillation following TAVR.

Serial changes in cardiac sympathetic nervous function after transcatheter aortic valve replacement: A prospective observational study using 123I-meta-iodobenzylguanidine imaging

BackgroundTranscatheter aortic valve replacement (TAVR) can rapidly improve cardiac sympathetic nervous function (CSNF) within 2 weeks in patients with aortic stenosis (AS). However, whether such short-term improvements will be sustained thereafter remains unclear. MethodsPatients with severe AS who underwent TAVR between October 2017 and June 2019 were enrolled in this single-center, prospective, observational study. 123I-meta-iodobenzylguanidine imaging was performed at baseline, within 2 weeks after TAVR, and at 6 to 12 months post-TAVR to evaluate the heart–mediastinum ratio (H/M) and washout rate. ResultsOf 183 consecutive patients, 75 (19 men; median age: 86 years) were evaluated. The late H/M significantly improved within 2 weeks after TAVR (P = .041) and further improved over 6 to 12 months after TAVR (P = .041). Multivariate analysis revealed that the baseline mean aortic valve pressure gradient (mPG) was an independent predictor of mid-term improvement in the late H/M (> 0.1) (P = .037). Patients with a high baseline mPG (≥ 58 mmHg) exhibited a significantly greater increase in the late H/M than those with a low baseline mPG (< 42 mmHg) (0.24 vs 0.01; P = .029). ConclusionCSNF demonstrated sustained improvement from within 2 weeks after TAVR until 6 to 12 months later. Such improvement was related to baseline hemodynamic AS severity.

Results of new-generation self-expanding transcatheter Porticoтм valve implantation in patients with degenerative aortic stenosis.

Aim To evaluate 30-day results of the transcatheter correction of degenerative aortic stenosis using a novel self-expandable valve, PorticoTM.Material and methods Transcatheter aortic valve implantation (TAVI) was performed in 42 patients with an intermediate surgical risk (mean age, 74.3±6.5 years, 8 men, 34 women, EuroSCORE II risk, 2.5 (1.5;4.1)) with severe degenerative aortic stenosis (AS). 20 (48 %) patients had ischemic heart disease; 8 (19%) of patients had atrial fibrillation, and 16 (38%) of patients had type 2 diabetes mellitus. Most of the patients (88 %) had preserved systolic function, and 5 patients had a pronounced decrease in left ventricular ejection fraction. Early efficacy and safety of the intervention were evaluated with VARC-2 criteria.Results In-hospital and 30-day mortality following TAVI was absent. Also, there were no adverse events, including cerebrovascular disorders, perioperative myocardial infarction, and conversion to open surgery. One patient had prosthesis migration to the aorta, which required implantation of the second self-expandable valve. Mean duration of the procedure was 90 min (80;110), fluoroscopy time was 21 min (19;24), and contrast volume 154 ml (200;240). Following TAVI, the mean aortic valve (AV) pressure gradient significantly decreased from 56.1±21.2 to 11.2±4.0 mm Hg, the maximal gradient decreased from 88.9±27.8 to 20.0±7.0 mm Hg, and the AV effective orifice area increased from 0.67±0.2 to 1.9±0.3 cm2 (p&lt;0.001). By the time of discharge from the hospital, all patients showed regression of AS clinical manifestations. The percentage of patients with NYHA functional class III chronic heart failure reduced from 62 % to 7 % (p&lt;0.001) after TAVI. In one case after the implantation, grade 3 aortic regurgitation was observed, which required endovascular occlusion to close the paraprosthetic fistula. Moderate paraprosthetic regurgitation (grade &lt;2) was observed in 3 (7 %) patients. Only 2 (4.8%) patients required permanent pacemaker implantation.Conclusion Results of the single-center prospective TAVI study using a novel self-expandable valve Porticoтм showed satisfactory hemodynamic parameters, efficacy and safety of the procedure for the 30-day follow-up period. A relatively low radial force of the carcass can be beneficial for reducing the incidence of permanent pacemaker implantation after TAVI.

Impact of atrial fibrillation on the symptoms and echocardiographic evaluation of patients with aortic valve stenosis

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Aarne Koskelo foundation and Helsinki University Hospital EVO funding Introduction Atrial fibrillation (AF) is common among patients with aortic valve stenosis (AS) and can cause similar symptoms. AF may also contribute to diastolic dysfunction. Since AF may alter the echocardiographic profile and provoke symptoms independent of AS, it may complicate the evaluation of AS severity and decision of the time for valve intervention. The purpose of this study was to assess the effect of AF on symptoms and the echocardiographic evaluation of AS. Methods We followed 192 patients (46% female) with suspected severe symptomatic AS who were referred to our institution for intervention. Echocardiography and symptom questionnaires were performed at baseline and 3 months after the intervention. Aortic valve calcium score was measured using computed tomography in the 121 patients considered for transcatheter intervention (TAVR). Results 52 of the 192 patients (27%) had AF. Patients with AF were older (median 81.5 [IQR 74.5-86.3] vs. 74 [64.0-81.3] years) and more often underwent TAVR (81% vs. 54%). In patients with AF the aortic valve mean pressure gradient was lower (39.5 [31.8-48.3] mmHg) than in patients without AF (46 [39.8-52.3] mmHg, p = 0.006, Fig.1A) and a low-gradient phenotype was more common (50% vs. 25% had mean gradient &amp;lt; 40 mmHg). There were no significant differences between groups in AVA, median EF or the proportion of patients with EF &amp;lt;50% (27% vs 17%). The aortic valve calcium score was similar in patients with or without AF (Fig.1B) and, based on the calcium score, 86% (AF) vs. 88% (no AF) of the patients were classified likely or very likely to have severe AS. AF patients had more advanced diastolic dysfunction as demonstrated by higher average E/e’ ratio (15.5 [12.9-20.2] vs. 12.4 [9.90-14.0], p &amp;lt;0.001), left atrial volume index (55.3 [42.0-62.7] vs. 36.7 [32.4-48.7] ml/m2, p &amp;lt;0.001) and tricuspid regurgitation gradient (35.0 [29.0-43.0 vs. 25.0 [23.0-29.0] mmHg, p &amp;lt;0.001). AF patients had worse functional class at baseline (49% vs. 27% with NYHA III or higher, p = 0.01, Fig.2A). There was significant improvement in both groups on follow-up (71% vs 72% improved at least one class), with no difference between groups. Dyspnoea, chest pain and exercise intolerance were equally frequent in patients with and without AF (Fig.2B). After intervention symptoms decreased significantly in both groups. Only exercise intolerance remained more common among AF patients (35% vs. 17%, p = 0.01). Conclusions AS patients with AF present more often with low-gradient phenotype and diastolic dysfunction, which may hamper the evaluation of AS severity. However, calcium score can serve as an alternative tool in the assessment of AS severity particularly in patients with AF and low gradient. Patients with AF are more symptomatic at baseline, but their symptoms improve significantly after intervention and nearly as well as in those without AF. Multiple imaging tools may be needed in decision-making in these patients. Abstract Figure 1 Abstract Figure 2

Proposal criteria of paradoxical low-flow low-gradient aortic stenosis for predicting prognosis in patients undergoing transcatheter aortic valve implantation.

Paradoxical low-flow, low-gradient (PLF-LG) aortic stenosis (AS) is associated with poor prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). This study aimed to verify the conventional criteria of PLF-LG AS (left ventricular ejection fraction [LVEF] > 50%, mean aortic valve pressure gradient [AVPG] < 40mm Hg and stroke volume index [SVI] < 35ml/m2 by measuring Doppler method) compatible for predicting prognosis in patients undergoing TAVI. A total of 128 consecutive patients who underwent TAVI for AS with LVEF > 50% were enrolled. The primary endpoint was the hospital readmission due to heart failure (HRHF) and the secondary endpoint was all-cause mortality after hospital discharge. The patients were classified by both the conventional criteria of PLF-LG AS and the proposal criteria of PLF-LG AS if mean aortic valve pressure gradient (AVPG) < 40mmHg and SVI by measuring Simpson's method < cut off value based on the ROC curve for predicting HRHF. According to the conventional criteria, only 6 patients were diagnosed with PLF-LG AS. However, according to the proposal criteria, 16 patients were diagnosed with PLF-LG AS. Fourteen patients developed HRHF during the follow-up period after TAVI. Based on the ROC curves, SVI by measuring Simpson's method (cut off value = 25ml/m2) had higher sensitivity and specificity for predicting HRHF (AUC = 0.74, p = 0.0013) than SVI by measuring Doppler method (AUC = 0.63, p = 0.045). The multivariate analysis revealed that PLF-LG AS defined by the proposal criteria (HR: 5.25; 95% CI: 1.60-17.16; p = 0.0073) but not by the conventional criteria was independently associated with HRHF. PLF-LG AS defined by the conventional criteria and the proposal criteria were not associated with all-cause mortality in the univariate analysis. Our results demonstrated that new criteria of PLF-LG AS defined as SVI < 25ml/m2 measured by Simpson's method could predict HRHF in patients with severe AS who underwent TAVI.

NATURAL HISTORY OF MITRAL ANNULUS CALCIFICATION AND CALCIFIC MITRAL VALVE DISEASE

<h3>BACKGROUND</h3> Mitral annular calcification (MAC) is a common finding, but the natural history and risk for developing calcific mitral valve disease (CMVD) have been poorly defined. We sought to evaluate the progression rate of MAC and of the development of CMVD. <h3>METHODS AND RESULTS</h3> Patients with at least mild MAC and paired echocardiograms at least one year apart between 2005 and 2019 were included. Progression rates from mild/moderate MAC to severe MAC and to CMVD (defined as severe MAC and significant mitral stenosis and/or regurgitation) were assessed, along with potential associations with sex and aortic valve stenosis (AS) progression. A total of 11,605 patients (73±10 years, 51% male) with MAC (78% mild, 17% moderate, 5% severe) were included and had a follow up echocardiogram at 4.2±2.7 years. In patients with mild/moderate MAC on their initial echocardiogram, the incidence of severe MAC at 10 years was 33%. The incidence was higher in females than in males (41% vs. 24%, P < 0.001, HR=1.3, P < 0.001) and in patients with moderate vs. mild MAC (71% vs. 22%, P < 0.001, HR=6.1, P < 0.001, see Figure 1). The overall incidence of CMVD at 10 years was 10% (4%, 23% and 60% in patients with mild, moderate, and severe MAC, respectively) and was predicted by female sex (15% vs. 5%, P < 0.0001), even after adjustment for MAC severity (HR=1.9, P < 0.001, see Figure 2). Patients who progressed to severe MAC had larger increases in aortic valve mean pressure gradient (AV MPG) (+4.1±4.5 vs. +3.3±3.6 mmHg/year, P < 0.001) that persisted after adjustment for age, sex, and baseline AV MPG. <h3>CONCLUSION</h3> In this large patient cohort with MAC, progression to severe MAC is common and frequently results in CMVD. Female sex was associated with higher progression rates and an association between MAC and AS progression was observed. MAC and CMVD are expected to dramatically increase as the population ages and there is an urgent need to better understand the pathophysiology of MAC in order to develop effective preventative medical therapies.

Incidence and Risk Factors of Pannus after Mechanical Aortic Valve Replacement.

This study was conducted to evaluate the occurrence rate and risk factors of subaortic pannus (SAP) after bileaflet mechanical aortic valve (AV) replacement. Between 1990 and 2014, 862 patients underwent primary AV replacement with bileaflet mechanical prosthesis. SAP was defined as (1) gradual increase in mean pressure gradient through mechanical AV without any evidence of motion limitation of the leaflets on echocardiography and (2) AV mean pressure gradient >40 mm Hg or AV peak velocity >4 m/s on echocardiography, and (3) any visible subaortic tissue ingrowth beneath the mechanical AV on echocardiography or computed tomography. Clinical and echocardiographic follow-up durations were 13.8 ± 8.0 and 10.7 ± 7.9 years, respectively. Mean age was 51.1 ± 12.1 years and concomitant surgeries were performed in 503 patients (58.4%). Overall survival at 10 and 20 years was 84.2 and 67.1%, respectively. SAP occurred in 33 patients, and in only 2 patients during the first 10 years after surgery. The cumulative incidence of SAP formation at 10, 20, and 25 years were 0.3, 5.0, and 9.9%, respectively. The Fine and Gray model demonstrated that small prosthetic valve size (hazard ratio [HR] [95% confidence interval, CI] = 0.738 [0.575-0.946]), young age (HR [95% CI] = 0.944 [0.909-0.981]), and concomitant mitral valve replacement (MVR) (HR [95% CI] = 3.863 [1.358-10.988]) were significant risk factors for the SAP formation. SAP occurred gradually over time with 10- and 20-year cumulative incidence of 0.3 and 5.0%, respectively. Young age, small prosthetic valve size, and concomitant MVR were risk factors for SAP formation. Therefore, we recommend efforts to select large prostheses for young patients requiring concomitant MVR.

Polish Multicenter Registry (Pol-LAS-SE registry). Stress echocardiography in low-gradient aortic stenosis in Poland: numbers, settings, results, complications and clinical practice.

The diagnostic workup of low-gradient aortic stenosis (LG AS) is a challenge in clinical practice. Our goal was to assess the diagnostic value of stress echocardiography (SE) performed in patients with undefined LG AS with low and preserved ejection fraction (EF) and the impact of its result on therapeutic decisions in Polish third level of reference. All the patients with LG AS and with SE performed were recruited in 16 Polish cardiology departments between 2016 and 2019. The main exclusion criteria were as follows: moderate or severe aortic or mitral regurgitation and mitral stenosis. The study group included 163 patients (52% males) with LG AS who underwent SE for adequate diagnostic and therapeutic decision. In 14 patients DSE was non-diagnostic. The mean aortic valve (AV) pressure gradient was 24.1 (7.3) mm Hg, while an AV area was 0.86 (0.2) cm2. Among 149 patients with conclusive DSE, severe AS was found in 59.8%, pseudo-severe in 22%, and moderate AS in 18%. There were no cases of death or vascular events related to DSE. Among 142 patients 63 (44%) patients had an aortic valve intervention in a follow-up (median: 208 days; lower-upper quartile: 73-531 days). Based on the result of the DSE test, severe AS was significantly more often associated with qualification to interventional treatment compared to the moderate and pseudo-severe subgroups (P <0.0001). The DSE test in severe AS is a valuable diagnostic tool in patients with LG AS in Poland.

BALLOON AORTIC VALVULOPLASTY WITH VALVER BALLOON CATHETER IN ADULTS WITH SEVERE AORTIC STENOSIS AS A BRIDGE OR PALLIATIVE TREATMENT

The aim: We aimed to assess the feasibility and safety of performing balloon aortic valvuloplasty (BAV) with Valver balloon catheter (Balton, Poland) in adults with severe aortic stenosis as a bridge or palliative treatment. Materials and methods: We identified consecutive patients who underwent BAV procedures between May 2019 and March 2020 using Valver balloon catheters. Demographic data, medical history, and clinical characteristics were retrospectively collected in all study patients together with periprocedural data as well as 12-month follow-up data. Results: We included 18 patients. The mean population age was 78.1±8.9 years, and women were 61.1%. The most common co-morbidities were arterial hypertension (88.9%), dyslipidemia (83.3%), and coronary artery disease (72.2%). The baseline mean aortic valve pressure gradient was 49.94±27.02 mmHg and the mean aortic valve area (AVA) was 0.65±0.20 cm2. In all cases, the procedure was performed from the femoral access via the 8F sheath. Two Valver balloon catheter sizes were used 18x40mm (33.3%) and 20x40mm (66.7%). Three periprocedural complications were observed, and none was associated with the Valver balloon catheter per se. The transthoracic echocardiography after the procedure revealed a decrease in the mean pressure gradient of 11.1±8.85 mmHg, and an increase in AVA of 0.21±0.19 cm2. At 12-month follow-up, the mortality rate was 38.9%. Conclusions: BAV is a procedure increasingly performed in catheterization laboratories worldwide. This paper confirmed the relative safety of BAV with Valver balloon catheters in the modern era, showing a low incidence of valve and vascular complications.

Markers of Elevated Left Ventricular Filling Pressure Are Associated with Increased Mortality in Nonsevere Aortic Stenosis

Echocardiographic measures of elevated left ventricular filling pressures are associated with an adverse prognosis. The aim of this study was to determine the relationship between acute (ratio of early transmitral flow to mitral annular velocity [E/e']) and chronic (indexed left atrial volume) markers of left ventricular filling pressure and mortality in patients with nonsevere aortic stenosis (AS), within the National Echo Database Australia cohort, testing the hypothesis that they would reflect the early hemodynamic consequences of AS and be associated with increased mortality in this setting. The first record for patients ≥18years of age showing hemodynamically significant but nonsevere (mild or moderate) AS (mean pressure gradient≥10 to <40mm Hg and aortic valve area > 1cm2) was analyzed. Baseline demographics and echocardiographic variables were compared with those among patients without AS (mean pressure gradient<10mm Hg). Mortality linkage data were available for all patients. Of 78,886 patients with aortic valve mean pressure gradients < 40mm Hg and aortic valve areas > 1cm2, 13,768 (17%) were identified with nonsevere AS (aortic valve mean pressure gradient 10-40mm Hg), of whom 57% were men (mean age, 73±13.4years) with a median follow-up of 3.4years (interquartile range, 1.7-6.1years). In unadjusted time-varying coefficient models, nonsevere AS and indexed left atrial volume > 34mL/m2 (hazard ratio [HR], 2.29; 95% CI, 2.03-2.58), E/e' ratio>14 (HR, 2.27; 95% CI, 2.08-2.49), left ventricular ejection fraction<50% (HR, 2.82; 95% CI, 2.50-3.19), and tricuspid regurgitation peak velocity>280cm/sec (HR, 2.54; 95% CI, 2.30-2.80) were associated with increased mortality hazard at the time of echocardiography. All markers were significant when combined in a multivariate model. Indices of elevated left ventricular filling pressure are independently associated with death in patients with nonsevere AS. Risk stratification models incorporating these variables may identify patients at risk for complications, warranting closer surveillance and possibly earlier intervention.

The effect of multiple-inflation balloon aortic valvuloplasty.

Recent improvements of balloon aortic valvuloplasty (BAV) devices and procedures have provided improved outcomes, but it is not clear whether the multiple-inflation BAV technique is effective in patients with symptomatic severe aortic valve stenosis (AS). We conducted an analysis of the impact of multiple-inflation BAV (at least 6 times inflation) on the mean aortic valve area (AVA) and mean aortic valve pressure gradient (AV-PG) in patients with symptomatic severe aortic stenosis as compared with conventional BAV (from single to three times inflation). We identified two studies of multiple-inflation BAV with antegrade approach using Inoue-balloon catheter (425 patients) and four studies of conventional BAV (170 patients) with retrograde approach. Using a random intercept model, we found that multiple-inflation BAV significantly increased mean AVA (mean difference (MD) [95% indicates confidence interval (CI)] = 0.25 [0.16-0.34], P < 0.001) and significantly decreased mean AV-PG (MD [95% CI] = - 20.2 [- 27.8, - 12.70], P < 0.001) as compared with the conventional BAV. Furthermore, despite an extremely high Society of Thoracic Surgeons (STS) score (9.2-14.5), the all-cause mortality rate at one year of multiple-inflation BAV was 16-17%. The results of our analyses indicate that the multiple-inflation BAV technique seem to be effective for patients with symptomatic severe AS as compared with conventional BAV.