Mean Aortic Pressure Gradient Research Articles

A propensity score matched analysis of transcatheter aortic valve replacement in failed bioprosthetic valves

Abstract Introduction While recently published data indicate similar long-term results of transcatheter aortic valve replacement (TAVR) compared to surgical procedures, surgical aortic valve replacement (SAVR) remains the standard of care in low-risk patients. However, since life expectancy increases, a non-negligible number of patients experience bioprosthetic valve dysfunction with the need for reintervention, but long-term data of TAVR in failed bioprosthetic valves is scarce. Purpose The aim of the study was to analyse long-term data of patients with TAVR in failed bioprosthetic valves compared to patients with native valve TAVR. The primary endpoint was 6-year all-cause mortality and the main secondary endpoint was echocardiographic valve function. Methods Patients undergoing TAVR for severe aortic valve disease between December 2012 and December 2020 were retrospectively analysed. Prior TAVR or aortic valve homografts led to exclusion from the study. A 2:1 propensity score matching by the optimal neighbor matching algorithm was performed to overcome differences in baseline characteristics. Results Between December 2012 and December 2020, 3,423 patients received TAVR for severe aortic valve disease and met inclusion criteria for the study. Of those, 3,287 patients underwent native valve TAVR, whereas 136 patients experienced bioprosthetic valve dysfunction and were treated with TAVR-in-SAV. After 2:1 propensity score matching, baseline characteristics without any relation to prior SAVR were similar between both groups. Concerning postprocedural echocardiographic function, a less pronounced gradient reduction (57.0 vs. 71.0 %, p < 0.01, Figure 1) and a higher number of patients with elevated mean pressure gradient > 20 mmHg could be found after prior SAVR (19.4 vs. 3.0 %, p < 0.01). However, there was no difference regarding 6-year all-cause mortality between both groups (log rank test p = 0.8, Figure 2). Conclusions Besides a less pronounced gradient reduction and higher mean aortic pressure gradients after TAVR-in-SAV compared to patients with native valve TAVR, no differences in 6-year all-cause mortality could be observed in a propensity score matched analysis.Reduction of mean pressure gradient6-year all-cause mortality

Abstract 15422: Diffuse Myocardial Fibrosis Predicts Outcome in Moderate and Asymptomatic Severe Aortic Stenosis

Introduction: Patients with moderate or asymptomatic severe aortic stenosis (AS) are at increased risk of cardiovascular events, but markers to guide intervention are lacking. We investigated the use of cardiovascular magnetic resonance (CMR) to identify drivers of outcome. Methods: Moderate (aortic valve area [AVA] 1.0-1.5 cm2) or asymptomatic severe AS patients (AVA≤1.0 cm2 and NYHA functional class I-II) (n=457) were prospectively enrolled from five international sites and parameters including extracellular volume fraction (ECV%) and late gadolinium enhancement were analyzed on CMR. Clinical events were defined as all-cause mortality and admission for heart failure. Results: Moderate AS patients had smaller left ventricular (LV) mass and less diastolic dysfunction compared to asymptomatic severe AS patients, but showed no difference in the extent of myocardial fibrosis and scar. During median 5.7-years follow-up, 83 clinical events occurred. Patients with clinical events had smaller AVA, greater diastolic dysfunction, and higher ECV% (median [interquartile range] ECV% 26.3% [24.3-29.8] vs 28.2% [25.5-30.8], P=0.003). There was a stepwise increase of clinical events across ECV tertiles. ECV% was associated with clinical outcome (adjusted HR 1.05, 95% CI 1.00–1.09, P=0.035), independent of AVA and aortic valve replacement as a time-dependent covariate. The prognostic significance of ECV% was consistent when AS severity was alternatively defined using aortic peak velocity and mean pressure gradient, and also across subgroups by AS severity and symptoms, AVA, aortic peak velocity, mean pressure gradient, and left ventricular ejection fraction (Figure). Conclusions: Increased diffuse myocardial fibrosis is associated with poor outcomes in moderate and asymptomatic severe AS patients and can help identify those who require closer surveillance and possibly earlier intervention.

Outcomes of Transcatheter Aortic Valve Replacement Patients With Different Transvalvular Flow-Gradient Patterns

Low-flow low-gradient (LF-LG) aortic stenosis (AS) may occur with preserved or depressed left ventricular ejection fraction (LVEF). Both situations represent the most challenging subset of patients to manage and generally have a poor prognosis. Few and controversial data exist on the outcomes of these patients compared with normal flow-high gradient (NF-HG) AS after transcatheter aortic valve replacement (TAVR). We sought to characterize different transvalvular flow-gradient patterns and to examine their prognostic value after TAVR. We enrolled 1,208 patients with severe AS and categorized as follow: 976 patients NF-HG (mean aortic pressure gradient [MPG] ≥40mm Hg), 107 paradoxical LF-LG (pLF-LG, MPG <40mm Hg, LVEF ≥50%, stroke volume index <35ml/m2), and 125 classical LF-LG (cLF-LG) (MPG <40mm Hg, LVEF <50%, stroke volume index <35ml/m2). When compared with NF-HG and pLF-LG, cLF-LG had a worse symptomatic status (New York Heart Association III to IV 86% vs 62% and 67%, p <0.001), a higher prevalence of eccentric hypertrophy and a higher level of LV global afterload reflected by a higher valvuloarterial impedance. Valvular function after TAVR was excellent over time in all patients. While 30-day mortality (p=0.911) did not differ significantly among groups, cLF-LG had a lower 5-year survival rate (LF-LG 50% vs pLF-LG 62% and NF-HG 68%, p <0.05). cLF-LG was associated with a hazard ratio for mortality of 2.41 (95% confidence interval 1.65 to 3.52, p <0.001). In conclusion, TAVR is an effective procedure regardless of transvalvular flow-gradient patterns. However, special care should be given to characterized hemodynamic of AS, as patients with pLF-LG had similar survival rates than patients with NF-HG, whereas cLF-LG is associated with a twofold increased risk of mortality at 5-year follow-up.

Aortic valve calcification is promoted by interleukin-8 and restricted through antagonizing CXCR2.

Inflammatory cytokines play a critical role in the progression of calcific aortic valve disease (CAVD), for which there is currently no pharmacological treatment. The aim of this study was to test the hypothesis that interleukin-8 (IL-8), known to be involved in arterial calcification, also promotes aortic valve calcification (AVC) and to evaluate whether pharmacologically blocking the IL-8 receptor, CXC motif chemokine receptor 2 (CXCR2), could be effective in preventing AVC progression. A cohort of 195 patients (median age 73, 74% men) diagnosed with aortic valve stenosis (severe in 16.9% of cases) were prospectively followed by CT for a median time of 2.6 years. A Cox proportional hazards regression analysis indicated that baseline IL-8 serum concentrations were associated with rapid progression of AVC, defined as an annualized change in the calcification score by CT ≥ 110 AU/year, after adjustment for age, gender, bicuspid anatomy and baseline disease severity. In vitro, exposure of primary human aortic valvular interstitial cells (hVICs) to 15 pg/ml IL-8 induced a two-fold increase in inorganic phosphate (Pi)-induced calcification. IL-8 promoted NFκB pathway activation, MMP-12 expression, and elastin degradation in hVICs exposed to Pi. These effects were prevented by SCH527123, an antagonist of CXCR2. The expression of CXCR2 was confirmed in hVICs and samples of aortic valves isolated from patients with CAVD, in which the receptor was mainly found in calcified areas, along with MMP-12 and a degraded form of elastin. Finally, in a rat model of chronic kidney disease-associated CAVD, SCH527123 treatment (1 mg/kg/day given orally for 11 weeks) limited the decrease in aortic cusp separation, the increase in maximal velocity of the transaortic jet, and the increase in aortic mean pressure gradient measured by echocardiography, effects that were associated with a reduction in hydroxyapatite deposition and MMP-12 expression in the aortic valves. Overall, these results highlight, for the first time, a significant role for IL-8 in the progression of CAVD by promoting calcification via a CXCR2-- and MMP-12-dependent mechanism that leads to elastin degradation, and identify CXCR2 as a promising therapeutic target for the treatment of CAVD.

Durability of bioprosthetic aortic valve replacement in patients under the age of 60 years - 1-year follow-up from the prospective INDURE registry.

We report 1-year safety and clinical outcomes in patients <60 years undergoing bioprosthetic surgical aortic valve intervention. The INSPIRIS RESILIA Durability Registry is a prospective, multicentre registry to assess clinical outcomes of patients <60 years. Patients with planned SAVR with or without concomitant replacement of the ascending aorta and/or coronary bypass surgery were included. Time-related valve safety, haemodynamic performance and quality of life (QoL) at 1 year were assessed. A total of 421 patients were documented with a mean age of 53.5 years, 76.5% being male and 27.2% in NYHA class III/IV. Outcomes within 30 days included cardiovascular-related mortality (0.7%), time-related valve safety (VARC-2; 5.8%), thromboembolic events (1.7%), valve-related life-threatening bleeding (VARC-2; 4.3%) and permanent pacemaker implantation (3.8%). QoL was significantly increased at 6 months and sustained at 1 year. Freedom from all-cause mortality at 1 year was 98.3% (95% confidence interval 97.1; 99.6) and 81.8% were NYHA I versus 21.9% at baseline. No patient developed structural valve deterioration stage 3 (VARC-3). The mean aortic pressure gradient was 12.6 mmHg at 1 year and the effective orifice area was 1.9 cm2. The 1-year data from the INSPIRIS RESILIA valve demonstrate good safety and excellent haemodynamic performance as well as an early QoL improvement. clinicaltrials.gov: NCT03666741.

Efficacy and safety of transcatheter aortic valve replacement in the treatment of severe aortic stenosis

Objective: To investigate the efficacy and safety of transcatheter aortic valve replacement (TAVR) in the treatment of severe aortic stenosis. Methods: The clinical data of patients with severe aortic stenosis who underwent TAVR at the People's Hospital of Xinjiang Uygur Autonomous Region between September 2016 and September 2022 were retrospectively analyzed. Changes in aortic transvalvular pressure gradients, valve orifice area, and activity tolerance of patients before and after the surgery were compared. Moreover, postoperative complications and follow-up results from 30 days to 6 years after the surgery were recorded. Results: A total of 76 patients were included in the study (50 males and 26 females), with an average age of (71.3±7.6) years, including 16 rheumatic valvular diseases, 60 senile degenerative diseases, 46 bicuspid valves and 30 tricuspid valves. The success rate of the operation was 96.1% (73/76). Compared with that before the operation, the mean aortic transvalvular pressure gradients decreased [(8.5±2.8) mmHg vs (68.5±19.2) mmHg (1 mmHg=0.133 kPa),P<0.001], but the valve orifice area increased [(1.91±0.31) cm2 vs (0.65±0.21) cm2, P<0.001]. Likewise, six-minute walking test (6MWT) showed that walking distance was longer after the surgery [(430±13) m vs (201±28) m, P<0.001]. There were 1 case of retroperitoneal hematoma, 1 case of stricture balloon dilatation after femoral artery suture concomitant with postoperative puncture site infection, 1 case of femoral artery surgical incision, 2 cases of valve-in-valve (ViV) and 5 cases of perivalvular leakage (4 cases were mild and 1 case was moderate) after the surgery, respectively. Moreover, acute left main artery occlusion during operation occurred in 1 case, ventricular rupture during operation occurred in 1 case and the patient was transferred to valve replacement surgery and finally dead, delayed coronary artery occlusion and death happened in 1 case, and all of the above-mentioned 3 cases were due to surgical failure. Postoperative pacemaker implantation due to third-degree atrioventricular block was performed in 5 cases. There were 1 case of pulmonary embolism, 1 case of transient right limb disorder, 1 case of gastrointestinal bleeding and 1 case of urethral bleeding after the surgery, respectively. The patients were followed up for (1.0±0.1) years (30 days to 6 years), and the results showed that 2 cases died, including 1 case died suddenly at home (the cause of death was unknown) and 1 case died of acute heart failure 8 months after the surgery. Chronic heart failure occurred repeatedly in 6 cases. The quality of life of other patients improved significantly. Conclusion: TAVR is effective and safe for patients with severe aortic stenosis.

Association between coronary flow and aortic stenosis during transcatheter aortic valve implantation.

In patients with aortic stenosis (AS), the coronary flow reserve decreases even in the absence of epicardial coronary artery stenosis. Systolic coronary flow reversal (SFR) reflecting reduced coronary microcirculation, often seen in patients with severe AS, has a potential negative impact on the pathogenesis of cardiac dysfunction. However, there are limited data on the relationship between the severity of AS and SFR, as well as on the benefits of transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the relationship between the severity of AS and efficacy of TAVI in improving SFR. Consecutive patients with AS who had undergone TAVI using transoesophageal echocardiography (TEE) from November 2020 to February 2022 were prospectively enrolled. Coronary flow in the left anterior descending artery as well as the aortic valve peak velocities, and the mean aortic valve pressure gradients (AVPGs), indicating the severity of AS, were measured using intraprocedural TEE before and after TAVI. The following parameters were measured as coronary flow: systolic and diastolic peak velocity (cm/s) and systolic and diastolic velocity-time integral (VTI) (cm). SFR was defined as the presence of a reversal coronary flow component in systole. The enrolled patients were classified into two groups according to the presence or absence of SFR before TAVI. A total of 25 patients were included: 13 had SFR and 12 who had no SFR, before TAVI. Patients with SFR had significantly higher aortic valve peak velocities (451.1±45.9 vs. 372.1±52.1cm/s; P<0.001) and mean AVPGs (49.2±14.5 vs. 30.3±11.6mmHg; P=0.002) than those without. The optimal binary cut-off aortic valve peak velocity values and the mean AVPG associated with the presence of SFR before TAVI were >410.0cm/s (specificity, 75.0%; sensitivity, 92.3%) and >37.4mmHg (specificity, 83.3%; sensitivity, 92.3%), respectively. After TAVI, SFR immediately disappeared in 11 of 13 patients with SFR (84.6%). Overall, the systolic coronary VTI significantly increased after TAVI (2.0±4.7 vs. 6.4±3.2cm, P<0.001), and this increase was greater in patients with SFR than in those without SFR before TAVI (interaction P=0.035). SFR was found to be associated with the severity of AS and with a greater increase in systolic coronary flow immediately after TAVI.

Prosthesis-Patient Mismatch after Aortic Valve Replacement with the Mosaic Ultra Bioprosthesis.

Several studies have reported high rates of prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) with the Mosaic prosthesis. This work assesses the incidence of PPM after AVR with a modified version of the Mosaic prosthesis, the Mosaic Ultra. We performed a retrospective analysis of the data of 532 patients who underwent AVR with implantation of the Mosaic Ultra prosthesis in the period 2007-2016 in our institution. Patients were classified according to their indexed effective orifice area (EOAi) to severe (EOAi < 0.65 cm2/m2), moderate (EOAi 0.65-0.85 cm2/m2), and absent/mild PPM (EOAi > 0.85 cm2/m2). In-hospital postoperative outcomes and the impact of PPM on mean transvalvular pressure gradient after stratification by prosthesis size were assessed. Overall, 3 (0.6%) patients had severe, 92 (17.3%) moderate, and 437 (82.1%) absent/mild PPM. There was a significant difference in PPM proportions (moderate/severe vs absent/mild PPM) across different prosthesis sizes overall (p < 0.0001), observing gradually increasing rates of PPM with decreasing prosthesis sizes. Patients with moderate/severe PPM had higher mean transvalvular pressure gradients (19 [13-25] vs 13 [10-17] mm Hg, p < 0.0001) than patients with absent/mild PPM. There was a significant difference in mean transvalvular pressure gradient between the different aortic valve prosthesis sizes overall (p < 0.0001), observing gradually increasing gradients with decreasing prosthesis sizes. Patients undergoing AVR with the smaller sized (19, 21, and 23 mm) Mosaic Ultra aortic valve prostheses exhibit a higher risk for moderate/severe PPM and higher mean aortic transvalvular pressure gradients than patients receiving the larger sized (25, 27, and 29 mm) prostheses.

Emergent transcatheter aortic valve implantation combined with enterectomy for acute decompensated heart failure caused by severe aortic stenosis and strangulated femoral hernia.

A 74-year-old female was admitted to our department with orthopnea, oliguria, and vomiting. She had a pacemaker implanted two years ago. Physical examination revealed an 8 cm × 6 cm bulge in the right groin. The transthoracic echocardiography showed that the area of aortic orifice was 0.4 cm2 and the left ventricle ejection fraction (LVEF) was 25%. The Society of Thoracic Surgeons score was 25.6%. Abdominal ultrasound demonstrated right femoral hernia with intestinal obstruction. Because of hemodynamic instability and the risk of intestinal necrosis, emergent transcatheter aortic valve implantation (TAVI) combined with hernia repair was scheduled to perform. The procedure was performed under general anesthesia with intubation. The transesophageal echocardiography (TEE) showed that the maximal and mean pressure gradient was 64 and 35 mmHg, respectively (Panels A–C); coronary angiography indicated no coronary artery stenosis. We chose left femoral artery access for TAVI through a totally percutaneous approach. According to TEE, aortic root angiography and based on the balloon pre-dilation (Panel D), 26 Venus-A self-expandable valve was successfully implanted (Panel F). And then, the right oblique cutdown was performed, and a tense hernial sac was revealed, in which we observed an 8-cm-long necrotic bowel (Panel E). The gastrointestinal surgeon had to resect the strangulated and anastomose the normal bowel. TEE showed that the maximal and mean aortic pressure gradient was 13 and 7 mmHg, respectively (Panels G and H). Thirteen days later after the operation, the patient was discharged from the hospital with no complications. Follow-up echocardiography demonstrated that the device position was appropriate, no perivalvular leakage, and the LVEF increased to 50%.

IL6 gene polymorphism association with calcific aortic valve stenosis and influence on serum levels of interleukin-6.

Aortic valve stenosis is the most frequent valve disease in developed countries and its prevalence will increase with population aging. There is still no pharmaceutical treatment nor biomarker to determine the susceptibility to develop aortic stenosis. Therefore, we analyzed the association of polymorphisms in risk loci with calcific aortic stenosis. Patients with aortic valve disease were genotyped for PALMD rs6702619, LPA rs10455872, and IL6 rs1800795 polymorphisms and circulating levels of interleukin-6 (IL-6) were measured. Calcium content of leaflets obtained in valve replacement surgeries was determined by micro-computed tomography. In the genotyping of 578 individuals, we found significant association between PALMD and IL6 polymorphisms and aortic stenosis in patients with tricuspid aortic valve, independently of other potentially confounding variables such as age and dyslipidemia. There was no association of these polymorphisms with valve calcium content, but this value correlated with the mean aortic pressure gradient (r = 0.44; P < 0.001). The CC genotype of IL6 polymorphism was associated with higher levels of serum IL-6 compared to other genotypes (23.5 vs. 10.5 pg/ml, respectively; P = 0.029). Therefore, patients carrying the CC genotype of IL6 rs1800795 polymorphism present higher levels of circulating IL-6 and this could contribute to the severity of the aortic valve stenosis. Our results agree with the identification of IL6 as a locus risk for stenosis and also with the intervention of this cytokine in aortic valve calcification. A more exhaustive follow-up of those patients carrying risk genotypes is therefore recommended.

High-sensitive Troponin T is not associated with the progression of asymptomatic mild to moderate aortic stenosis: a post hoc substudy of the SEAS trial

Abstract Background Aortic stenosis (AS) and coronary artery disease (CAD) share pathophysiological pathways, as reflected by frequent concomitant revascularization in patients undergoing aortic valve replacement (AVR). High-sensitive Troponin T (hsTnT) is a proven biomarker of cardiomyocyte overload and injury, and predicts postoperative mortality after AVR. However, it is unknown if hsTnT can predict AVR, mortality or ischemic coronary events (ICE) in asymptomatic AS patients. Purpose To investigate the hypothesis that increased hsTnT is associated with more severe AS and a higher risk of adverse outcomes in asymptomatic AS patients without overt CAD. Methods hsTnT concentrations were examined at baseline and after 1-year follow-up in 1739 asymptomatic AS patients enrolled in the randomized, double-blind Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. The main inclusion criteria were: left ventricular (LV) ejection fraction &amp;gt;55%, transaortic maximal velocity between 2.5–4.0 m/s, and no history of CAD. The primary exposure variable was increased hsTnT (&amp;gt;14 pg/mL according to the assay manufacturer, Roche). This study's primary endpoint was a composite of competing risk outcomes: all-cause mortality as the first event, AVR without revascularization, and ICE (defined as myocardial infarction before AVR, PCI before or combined with AVR, or any CABG). Multivariable regression examined associations between hsTnT and clinical variables. Cox proportional hazards regression models were adjusted for age, sex, creatinine, LV mass index, mean aortic pressure gradient (Pmean) and stratified by center and lipid-lowering treatment. We analyzed outcomes during 5-year follow-up from baseline. Results At baseline, 453 (26.0%) patients had increased hsTnT and 302 (17.4%) had moderate-severe AS with a mean (SD) aortic valve area of 0.8 (0.2) cm2 and Pmean of 33.2 (8.8) mmHg. The median annual hsTnT change from baseline to year 1 was 0.8 pg/mL (IQR, −0.4 to 2.3), regardless of AS severity (P=0.08). In adjusted models, log(hsTnT at baseline) was associated with age, sex, creatinine, and LV mass index (all P&amp;lt;0.05), but not with AS severity (P=0.36). The incidence rate ratio for ICE (Figure 1) in patients with increased vs normal baseline hsTnT concentrations was 2.32 (95% CI, 1.72–3.11, P&amp;lt;0.001). In adjusted Cox regression, increased hsTnT was associated with an increased 5-year ICE risk (HR 1.64; 95% CI, 1.18–2.29, P=0.003), but neither with AVR without revascularization nor death (Figure 1). Conclusion In these asymptomatic AS patients without overt CAD, hsTnT is often normal and remains stable during 1 year of follow-up regardless of AS severity. Increased hsTnT is associated with CAD-related events, but neither to AS severity nor AVR without concomitant revascularization. This analysis does not support routine hsTnT measurement in asymptomatic AS to predict AVR related to AS progression, although hsTnT could improve the risk assessment for ICE. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Main sponsor (SEAS): Merck &amp; Co Inc, Whitehouse Station, New JerseyBlood analysis sponsor: Roche Diagnostics International Ltd, Switzerland

Serial measurements of myocardial efficiency in patients with aortic valve stenosis: pathophysiological insights and prognostic information

Abstract Background In patients with aortic valve stenosis (AS), the pathophysiological abnormalities involved in the transition to symptomatic heart failure are unclear. During progression of chronic heart failure, the coupling between myocardial stroke work and myocardial oxygen consumption, i.e. myocardial external efficiency (MEE), deteriorates. However, in AS patients it is unknown whether changes in MEE over time are involved in disease progression and whether MEE has prognostic information. Purpose In patients with AS, we 1) investigated changes in MEE over time and 2) studied if MEE was associated with long-term prognosis. Methods In a prospective design, we studied 10 healthy controls and 38 patients with moderate-severe, asymptomatic AS (aortic valve area 0.5±0.1 cm2/m2, mean gradient 31±12 mmHg) and left ventricular ejection fraction ≥50%. The patient group was evaluated by serial 11C-acetate positron emission tomography, cardiovascular magnetic resonance imaging and echocardiography with a median follow-up period of 2.8 years. Furthermore, we conducted an extended follow-up of patients for a median of 5.2 years to detect clinical events (defined as symptoms due to AS, aortic valve replacement, hospitalization due to heart failure or cardiovascular death) and related them to MEE changes. Results During follow-up AS patients mean aortic valve pressure gradients increased by 13 mmHg (9 to 17; p&amp;lt;0.001) (mean (95% confidence interval)) and aortic valve opening area declined by −0.15 cm2 (−0.20 to −0.09; p&amp;lt;0.001). Global longitudinal strain worsened by 2.6% (1.8 to 3.5; p&amp;lt;0.001) and N-terminal pro-B-type natriuretic peptide increased by 162 ng/L (28 to 296; p=0.02) whereas left ventricular ejection fraction and cardiac index did not change significantly. MEE increased during follow-up by 4.3% (1.9 to 6.8; p=0.001) from 25.2% (24.0 to 26.5) to 29.5% (27.3 to 31.8) and was higher compared to healthy volunteers 19.9% (18.1 to 21.8; p&amp;lt;0.001). The changes in MEE were positively correlated to changes in end-diastolic volume (r=0.58, p=0.005) and wall stress (r=0.54, p=0.01). There were no changes in MVO2 0.0 mL/min/100g (−0.8 to 0.8; p=0.98) during follow-up. As compared to event-free patients, patients who experienced a clinical event during long-term follow-up (n=24, 63%) had higher baseline MEE 26.5% (24.3 to 28.6) vs 23.8% (22.6 to 25.1) (p=0.04) and did not increase MEE during follow-up 1.9% (−1.8 to 5.6; p=0.28) vs 5.9% (2.6 to 9.2; p=0.002). Conclusion In asymptomatic AS patients, MEE increased over time in tandem with increasing transvalvular gradients and wall stress. Thus, the myocardium displayed an inherent capacity to improve the coupling between oxidative metabolism and contractile function in response to pressure overload. High baseline MEE and blunted MEE increase predicted a poor prognosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Lundbeck FoundationArvid Nilssons Foundation

Early Hemodynamic Outcomes in Self-Expandable Valves: Comparison of ACURATE Neo Versus ACURATE Neo2

BackgroundComparisons of hemodynamic results between ACURATE Neo and ACURATE Neo 2, which have updated outer sealing skirts, are limited. This retrospective study aimed to demonstrate the differences in hemodynamic outcomes between the two transcatheter heart valves (THVs). MethodsWe included 449 patients who underwent transfemoral transcatheter aortic valve replacement (TAVR) with either ACURATE Neo2 (n = 100) or ACURATE Neo (n = 348) between January 2016 and November 2021. The primary endpoint was the incidence of moderate or severe paravalvular leakage (PVL). The mean aortic pressure gradient (APG), peak aortic velocity (AV), and early clinical outcomes were assessed as secondary outcomes. ResultsIn the propensity-score matching comparison (94 pairs), there were no significant differences in the incidence of moderate or severe PVL (4.3 % in Neo2 group vs. 8.5 % in Neo group, p = 0.233), and peak AV and mean APG were significantly higher in Neo2 group (Peak AV: 2.1 ± 0.4 vs. 1.9 ± 0.5 m/s, p = 0.003; mean APG: 10.6 ± 4.8 vs. 9.0 ± 6.1 mmHg, p = 0.045). In the multivariate logistic regression analysis, the THV type (ACURATE Neo2) was not an independent predictor of moderate or severe PVL. ConclusionThe incidence of moderate or severe PVL did not significantly differ between TAVR with ACURATE Neo2 and ACURATE Neo; however, it was numerically lower in ACURATE Neo2. In contrast, the Neo2 group had a higher residual mean APG and peak AV. A larger study with long-term follow-up is warranted to assess the clinical relevance of these findings.

Preoperative hypomagnesemia as a possible predictive factor for postoperative increase of transvalvular pressure gradient in hemodialysis patients treated with transcatheter aortic valve implantation

Background Patients undergoing maintenance hemodialysis (HD) with severe aortic stenosis are at a high risk for bioprosthetic valve dysfunction after transcatheter aortic valve implantation (TAVI). Currently, preoperative factors that predict the occurrence of valve dysfunction after TAVI on HD patients remain to be elucidated. The aim of this study is to analyze the association between preoperative clinical factors and valve stenosis after TAVI on HD patients. Methods Twenty-four of HD patients who underwent TAVI at our institution between April 2012 and January 2016 were analyzed. The mean aortic transvalvular pressure gradient (MPG) and effective orifice area index (EOAi) were assessed by serial echocardiography. Associations between preoperative clinical factors and time-series changes in MPG were examined using mixed-effects linear regression model for repeated measures. Results Three patients developed severe structural valve deterioration with calcific valve stenosis requiring reoperation. A multivariate linear mixed-effects model showed that lower serum magnesium (sMg) levels were associated with the increase of MPG after TAVI (beta-coefficient = 0.019, p = 0.03). No correlation was observed with serum calcium, phosphorus, or intact parathyroid hormone. Time-series changes of MPG and EOAi had significant difference between lower and higher sMg group. All 3 of the patients who underwent reoperation showed lower preoperative sMgs. Conclusion Among bone-mineral metabolism markers, preoperative hypomagnesemia was associated with the increase of MPG after TAVI, suggesting that hypomagnesemia could predict post-TAVI valve dysfunction in HD patients. Further studies with larger sample sizes are warranted.

Relation of Monocyte Number to Progression of Aortic Stenosis

Rapid progression of aortic stenosis (AS) is associated with poor prognosis. However, the relation between monocyte number and AS progression is unknown. Here, we detected the relation between monocyte number and AS progression. We retrospectively analyzed 220 patients with AS with at least 2 echocardiograms with the maximal interval ≥180days from January 2016 to June 2021. AS severity was categorized by aortic jet velocity (Vmax) and mean pressure gradient. Rapid progression of AS was defined when Vmax increased ≥0.3m/s/year. Patients were divided into low and high monocyte groups according to the cut-off value of the receiver-operating characteristic curve. AS progression was compared between the 2 groups. Various models of binary logistic regression were used to reveal the association between monocyte number and rapid progression. During a median of 601days of echocardiographic follow-up (interquartile range 353 to 909), 52.7% of the population was in rapid progression. Patients in the high monocyte group had more rapid progression in both Vmax and mean pressure gradient (p=0.020 and p=0.030, respectively). The percentage of patients with severe AS was increased by 5.4% in the low monocyte group and 16.9% in the high monocyte group. Different models of binary logistic regression showed that the monocyte number was positively associated with the rapid progression. In conclusion, a higher monocyte number was associated with the rapid progression of AS.

Diabetes Is Associated With Rapid Progression of Aortic Stenosis: A Single-Center Retrospective Cohort Study

BackgroundMounting evidence indicates that rapid progression of aortic stenosis (AS) is significantly associated with poor prognosis. Whether diabetes accelerates the progression of AS remains controversial.ObjectivesThe purpose of the present study was to investigate whether diabetes was associated with rapid progression of AS.MethodsWe retrospectively analyzed 276 AS patients who underwent transthoracic echocardiography at least twice with a maximum interval ≥ 180 days from January 2016 to June 2021. AS severity was defined by specific threshold values for peak aortic jet velocity (Vmax) and/or mean pressure gradient. An increase of Vmax ≥ 0.3 m/s/year was defined as rapid progression. The binary Logistic regression models were used to determine the association between diabetes and rapid progression of AS.ResultsAt a median echocardiographic follow-up interval of 614 days, the annual increase of Vmax was 0.16 (0.00–0.41) m/s. Compared with those without rapid progression, patients with rapid progression were older and more likely to have diabetes (P = 0.040 and P = 0.010, respectively). In the univariate binary Logistic regression analysis, diabetes was associated with rapid progression of AS (OR = 2.02, P = 0.011). This association remained significant in the multivariate analysis based on model 2 and model 3 (OR = 1.93, P = 0.018; OR = 1.93, P = 0.022). After propensity score-matching according to Vmax, diabetes was also associated rapid progression of AS (OR = 2.57, P = 0.045).ConclusionsDiabetes was strongly and independently associated with rapid progression of AS.

Clinical and echocardiographic parameters associated with left ventricular recovery after TAVI

Abstract Introduction The relationship between severe Aortic Stenosis (AS) and Left Ventricular (LV) dysfunction is well established. However, there is a paucity of data regarding LV functional recovery after TAVI. Purpose To study the clinical and echocardiographic parameters associated with LV functional recovery after TAVI. Methods We evaluated all patients who underwent TAVI between 2009–2020 in a tertiary medical center. We included patients with pre-procedural LV Ejection Fraction (LVEF) of 40% and below. All patients had baseline and in-hospital post-procedural echo, and their clinical characteristics were recorded in a designated TAVI registry. LV functional recovery was defined as an absolute increase in at least 10% in LVEF post-procedurally. No LV recovery was defined as an absolute change of up to ±10% in post-procedure LVEF, and LVEF deterioration was defined as an absolute decrease of more than 10% in post-procedural LVEF compared to baseline. Univariate analysis consisting clinical and echocardiographic factors for LV functional recovery was performed, followed by logistic regression adjusting for confounders. Results Out of 1,349 consecutive TAVI patients, 100 (7.4%) had LVEF of 40% or less. There were 69 (69%) men with a mean age of 82±8 years, and average BMI of 27±4 kg/m2. Prior coronary artery disease and hypertension were present in 34 (34%) and 21 (21%) of patients, respectively. Out of these 100 patients, 32 (32%) had achieved LV functional recovery and no patient had experienced LVEF deterioration (FIGURE). Mean Left Ventricular End Systolic Diameter (LVESD) was 3.79 and 4.43 in the LV functional recovery and no LV recovery groups, respectively. Mean aortic pressure gradient was higher among patients who had LV functional recovery compared to no LV recovery (45.9 vs. 31.5 mmHg, respectively). Multivariable analysis revealed parameters that were independently associated with LV functional recovery: Coronary artery disease – OR 5.29 (95% CI 1.59–20.44), LVESD – OR 0.87 (95% CI 0.8–0.95) for each 1 mm increment and mean aortic pressure gradient – OR 1.91 (95% CI 1.21–3.28) per each 10 mmHg increment. Conclusion In patients with severe AS and LV dysfunction undergoing TAVI, the presence of coronary artery disease, increased aortic pressure gradient and reduced LVESD were associated with early LV functional recovery. Funding Acknowledgement Type of funding sources: None. Figure 1

Comparison of Echocardiographic Variables in Patients With Severe Aortic Stenosis and Preserved Ejection Fraction Grouped by Flow and Gradient

The pathophysiology of severe aortic stenosis (AS) is complex with vascular, valvular, and myocardial components. To better define this process, we compared echocardiographic and clinical variables in patients with severe AS and preserved EF according to flow and gradient. We retrospectively studied the clinical and echocardiographic data of 287 patients (mean age 76 ± 11 years, 57% men) from 2012 to 2017 with severe AS (indexed aortic valve area <0.6 cm2/m2) and preserved ejection fraction (>50%). Patients were divided into 4 groups based on flow (stroke volume index < or ≥35 ml/m2) and mean aortic pressure gradient (< or ≥40 mm Hg): normal flow, high gradient (NFHG), normal flow, low gradient (NFLG), low flow, high gradient (LFHG) and low flow, low gradient (LFLG). Among patients with severe AS, 23% had NFHG, 44% had NFLG, 10% had LFHG, and 23% had LFLG. Only diabetes was marginally significantly different among the clinical variables. Aortic valve area index was largest in NFLG and smallest in LFHG (p < 0.001 for pairwise comparisons). Valvuloarterial impedance was highest in LFHG (p < 0.01 for pairwise comparisons). Systemic arterial compliance was lower and systemic vascular resistance was higher in low flow compared with normal flow groups. In conclusion, LFHG had the smallest valve area index along with markers of increased vascular resistance combined with high gradients, which suggests a unique pathophysiology in this group of severe AS patients with preserved EF.

Deoxyribonuclease is prognostic in patients undergoing transcatheter aortic valve replacement.

Degenerative aortic valve stenosis is an inflammatory process that resembles atherosclerosis. Neutrophils release their DNA upon activation and form neutrophil extracellular traps (NETs), which are present on degenerated aortic valves. NETs correlate with pressure gradients in severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) is an established treatment option for aortic valve stenosis. Bioprosthetic valve deterioration promoted by inflammatory, fibrotic and thrombotic processes limits outcome. Deoxyribonuclease is a natural counter mechanism to degrade DNA in circulation. In the present observational study, we investigated plasma levels of double-stranded DNA, deoxyribonuclease activity and outcome after TAVR. 345 consecutive patients undergoing TAVR and 100 healthy reference controls were studied. Double-stranded DNA was measured by fluorescence assays in plasma obtained at baseline and after TAVR. Deoxyribonuclease activity was measured at baseline using single radial enzyme diffusion assays. Follow-up was performed at 12months, and mean aortic pressure gradient and survival were evaluated. Receiver operating characteristic, Kaplan-Meier curves and Cox regression models were calculated. Baseline double-stranded DNA in plasma was significantly higher compared to healthy controls, was increased at 3 and 7days after TAVR, and declined thereafter. Baseline deoxyribonuclease activity was decreased compared to healthy controls. Interestingly, low deoxyribonuclease activity correlated with higher C-reactive protein and higher mean transaortic gradient after 12months. Finally, deoxyribonuclease activity was a strong independent predictor of outcome 12months after TAVR. Deoxyribonuclease activity is a potential biomarker for risk stratification after TAVR. Pathomechanisms of bioprosthetic valve deterioration involving extracellular DNA and deoxyribonuclease merit investigation.

Clinical outcomes after implantation of a sutureless aortic bioprosthesis with concomitant mitral valve surgery: the SURE-AVR registry

BackgroundEarly treatment of aortic valve stenosis is recommended in eligible symptomatic patients with severe aortic valve stenosis who would otherwise have a poor prognosis. The sutureless aortic valve bioprosthesis offers an alternative to standard aortic valve replacement with a sutured valve, but limited data are available in patients who have undergone multiple valve procedures involving the new, sutureless technology. We sought to investigate outcomes in high operative risk patients with previous or concomitant valve surgery who were implanted with a sutureless valve.MethodsSURE-AVR is an ongoing, prospective, multinational registry of patients undergoing aortic valve replacement. In-hospital and post-discharge outcomes up to 5 years were collected.ResultsThe study population comprised 78 patients (mean ± SD: age 73.6 ± 7.6 years, logistic EuroSCORE 18.0 ± 17.5) enrolled at 13 sites who presented for concomitant or previous mitral valve repair (n = 45) or replacement (n = 33), with or without additional concomitant procedures, and were implanted with a sutureless valve. Mean ± SD overall aortic cross-clamp time was 109 ± 41 min and cardiopulmonary bypass time was 152 ± 49 min. Mean ± SD aortic pressure gradients decreased from 37.6 ± 17.7 mmHg preoperatively to 13.0 ± 5.7 mmHg at hospital discharge, and peak aortic pressure gradient from 61.5 ± 28.7 to 23.4 ± 10.6 mmHg. Early events included 1 death, 1 transient ischaemic attack, and 1 bleed (all 1.3%); a permanent pacemaker implantation was required in 6 patients (7.7%), and 2 reoperations (not valve related) (2.6%) took place. Over a median follow-up of 55.5 months (Q1 13.4, Q3 68.6), 12 patients died (6 cardiovascular and 6 non-cardiovascular, both 2.1% per patient-year). Five-year survival was 81.3%. Late paravalvular leak occurred in 2 patients (0.7% per patient-year) and permanent pacemaker implantation was required in 3 patients (0.1% per patient-year). There was no apparent rise in mean or peak aortic pressure gradient over the study.ConclusionsThese results suggest that the sutureless implant is a technically feasible procedure during mitral surgery and is associated with good clinical outcomes.