Pressure Gradient Research Articles

Right ventricular myocardial work predicts heart failure hospitalizations irrespective of ejection fraction

Abstract Hospitalization for heart failure worsening (HFW) associates with increased subsequent rehospitalization rate and mortality irrespective of left ventricular ejection fraction (EF). However there’s little evidence regarding predictors of HFW to timely apply preventive measurements. Since right ventricular (RV) dysfunction often associates with more advanced stages of HF we assumed that RV myocardial work (MW) assessment might be used in prediction of HFW. Methods 158 patients with HF (48% female) 58±7 years on guideline directed medical therapy in sinus rhythm and with at least one hospitalization in the last 6 months were enrolled in the study. Patients with HFrEF, HFmrEF and HFpEF were evenly represented. All patients were appropriately decongested prior to the study. The primary outcome was rehospitalization, HFW or cardiovascular death. RVMW was derived from RV global strain, including interventricular septum, and noninvasively estimated pulmonary arterial pressure (PAP). Systolic PAP (sPAP) was measured as the sum of maximum RV and right atrial (RA) pressure gradient (PGmax) from tricuspid regurgitation (TR) jet peak velocity and mean right atrial pressure (RAP) estimated from diameter and collapsing of inferior vena cava. Mean PAP (mPAP) was measured as the sum of PGmean RV-RA by tracing TR jet and RAP. Diastolic PAP was estimated as dPAP = 1.5 × [mPAP − (sPAP/3)]. Then RV global work index (RVGWI), constructive (RVGCW), and efficient work (RVGWE) were derived by the software dedicated for left ventricular MW. Left ventricular global longitudinal strain, left atrial (LA) reservoir strain (LAS), LA pump strain, LA volume index (LAVi), B lines, inferior vena cava, NT-pro-BNP, TAPSE/sPAP and RVMW were also measured. Patients followed up for 12 months. Results 53 events were registered at 12 months of which 42 rehospitalizations due to HFW and 11 CV deaths. Among all parameters in the multivariate analysis lower RVGCW was associated with HFW (HR 0.978, 95% CI 0.973–0.998, p = 0.014). RVGCW was the most powerful predictor of CV events (AUC 0.91) with cut off value of 148 mmHg% that had 96% sensitivity and 88% specificity. Number of patients who died with RVGCW < 148 mmHg% was 8 of 11 (73%) total deaths (HR 0.421, 95% CI 0.083–0.986, p = 0.028). Conclusion RVGCW was a predictor of HFW and 1 year mortality in patients with HF irrespective of EF.

Diagnostic value of low dose dobutamine stress echocardiography in paradoxical low flow low gradient aortic stenosis

Abstract Background In aortic stenosis with low-gradient scenarios distinguishing between fixed and pseudo-severe stenosis becomes challenging. Low-dose dobutamine stress echocardiography (DSE) is recommended for classical low-flow low- gradient stenosis with reduced ejection fraction. Doubts of DSE's utility in paradoxical low-flow low-gradient (PLFLG) stenosis when ejection fraction is preserved are partially reasoned by proposed inefficiency in generating a contractile reserve 1. Guidelines advocate an integrated approach, combining various clinical and imaging aspects 2. Purpose This study aimed to investigate usefulness of DSE in PLFLG stenosis, identifying specific features to predict the possibility of generating significant stroke volume augmentation and distinguishing fixed aortic stenosis. Methods We identified patients with aortic stenosis who underwent DSE and multi-modality imaging at our centre between 2020 and 2023. Among them, those with PLFLG situations were used for detailed analysis. Multiple linear regression analysis was performed to identify parameters predictive of significant contractile reserve, defined as 20% stroke volume increase from baseline. For patients demonstrating contractile reserve we assessed predefined parameters by receiver operating characteristics (ROC) analysis to predict fixed stenosis defined as final aortic valve area < 1cm² and valve area change <0.2cm² or final mean pressure gradient >40mmHg. For predictive value of Agatston score we conducted post-hoc analysis. Results Among 256 DSE cases, 67 were conducted for PLFLG stenosis. Patients were 82 years of median age and mostly female (63%). Symptoms included dyspnea in 90% and angina in 40% of cases. Baseline echo showed median aortic valve area (indexed to body surface area) of 0.8cm² (0.44cm²/m²) with mean pressure gradient of 20mmHg. Contractile reserve was inducible in 70% of patients, of which 74% showed criteria of fixed stenosis. Higher left ventricular end-diastolic diameter (LVESD) and lower baseline systolic flow-rate were predictive for contractile reserve (p<0.05). Among patients with contractile reserve ROC for baseline mean pressure gradient, acceleration time (median 0.08s; range 0.04-0.11s) and acceleration time to ejection time index (0.28; range: 0.148-0.458) revealed good prediction of fixed stenosis in DSE meanwhile Agatston calcium score (median 1076; range: 301-8821) did not (figure 1). No correlation was found between Agatston score probability of severe stenosis and aortic valve pressure gradient behavior with increased stroke volume (figure 2). Conclusion DSE proves to be a useful a method in the differentiation between fixed and pseudo-severe stenosis in PLFLG situation. Our findings question the predictive value of Agatston score for aortic valve behavior with increase of stroke volume and warrant further investigations regarding value of acceleration time and acceleration time to ejection time index in those patients.Receiver operating characteristicsPost-hoc analysis of Agatston score

The comparison of echocardiographic and serum parameters between Sapien 3 Ultra Resilia and Sapien 3 at one month

Abstract Background Sapien 3 Ultra Resilia (S3UR) is the latest balloon-expandable valve for transcatheter aortic valve replacement (TAVR). Compared to Sapien 3 (S3), previous model of balloon-expandable valve, the leaflets are modified to anti-calcification tissue and the outer skirt becomes 40% higher with textured polyethylene terephthalate. However, it is unknown how these structural changes affect echocardiographic and serum parameters after TAVR. Purpose To compare impacts of these design changes on relevant echocardiographic and serum parameters between S3UR and S3 in the short term. Methods Patients with severe aortic valve stenosis who underwent TAVR with S3 or S3UR were included in this study. Echocardiographic parameters and blood samples were retrospectively collected at discharge and at 1 month post-procedure. Echocardiographic outcomes included mean pressure gradient (PG), effective orifice area index (EOAi), and paravalvular leak (PVL) grade. Hemolytic anemia indicators, specifically lactate dehydrogenase (LDH) and hemoglobin (Hb), were also assessed. Findings suggestive of hemolytic anemia at 1 month were defined as "an increase in LDH level of ≧200 IU/L as well as a decrease in Hb level of ≧1.0 g/dL from pre-procedure." Results Among 443 patients (S3: April 2020-March 2023, S3UR: April 2023-December 2023), 339 patients (S3: n=270, S3UR: n=69) were available for this study. The mean PG was significantly lower in the S3UR group compared to the S3 group at discharge and at 1 month (Figure 1A). On the other hand, the EOAi was similar between the two groups at discharge and at 1 month (Figure 1B). Although the prevalence of none/trace PVL was significantly higher in the S3UR group at discharge, this difference disappeared at 1 month (Figure 1C). LDH levels were significantly increased from pre-procedure to 1 month in both groups (Figure 2A). The median of ΔLDH (1 month – pre-procedure) and %change of LDH (ΔLDH/ pre-procedure) were significantly higher in the S3UR group. The prevalence of hemolytic anemia at 1 month was also significantly higher in this group (Figure 2B). Conclusion At 1 month, S3UR demonstrated superiority in mean PG but equivalence in EOAi and PVL grade compared with S3. Although both S3UR and S3 showed significant increase in LDH from pre-procedure to 1 month, hemolytic anemia was experienced more frequently in S3UR cases. Further evaluation will be needed to assess the potential clinical impacts of these differences.

Evolution and prognostic impact of left ventricular myocardial work indices after transcatheter aortic valve replacement in patients with severe aortic stenosis

Abstract Introduction Left ventricular myocardial work (LVMW) is an echocardiographic-based technique to evaluate LV function using pressure-strain loops and therefore correcting for the left ventricular (LV) afterload. LVMW indices have been shown to be of prognostic importance in patients with aortic stenosis (AS) before transcatheter aortic valve replacement (TAVR), but no data is available on the evolution and the prognostic value of these parameters after TAVR. Purpose To measure LVMW indices before and after TAVR in patients with severe AS and explore the association with outcome. Methods As previously validated, LV global longitudinal strain (GLS) and LV systolic pressure (as the sum of the brachial arterial blood pressure and mean aortic valve gradient before TAVR and as brachial arterial blood pressure after TAVR) were incorporated to build pressure-strain loops and to calculate the following LVMW indices: global work index (LV GWI), global constructive work (LV GCW), global wasted work (LV GWW) and global work efficiency (LV GWE). The endpoint was all-cause mortality. Results A total of 255 patients were included with a median age of 82 years (IQR 77-85); 51% were men and 67% presented with NYHA class III/IV. After TAVR, LVEF and LV GLS remained in average unchanged (from 56 to 55%, p=0.470 and from 13.6 to 13.2%, p=0.068). While LV GWW remained unchanged after TAVR (from 247 to 258mmHg%, p=0.080), LV GWI, LV GCW and LV GWE significantly decreased (from 1882 to 1291mmHg%, p <0.001, from 2248 to 1671mmHg%, p <0.001 and from 89 to 85%, p <0.001 respectively). During a median follow-up of 59 months (IQR 40-72), 129 patients died. Univariable Cox regression analysis identified an association between all-cause mortality and male sex, diabetes mellitus, chronic obstructive pulmonary disease (COPD), renal function, atrial fibrillation, Charlson comorbidity index, pacemaker implantation, and post-TAVR LV GLS, LV GWI and LV GCW. These clinical parameters were used as a basal multivariable Cox regression model of which on top either post-TAVR LV GLS, LV GWI or LV GCW were added. All these parameters of post-TAVR LV systolic function showed an independent association with all-cause mortality, but LV GWI demonstrated the highest increase in model predictivity (Figure 1). Given the prognostic relevance of post-TAVR LV GWI, the population was divided into LV GWI tertiles. The group with the lowest LV GWI tertile showed a significantly higher proportion of male patients, higher prevalence of atrial fibrillation and also worse pre-TAVR LVEF, LV GLS, LV GWI, LV GCW and LV GWE. Kaplan Meier survival analysis confirmed the worse survival in the group with the lowest LV GWI compared to the highest tertile (log-rank ꭓ2: 8,224, p 0.016, Figure 2). Conclusion LVMW indices change after TAVR and post-TAVR LV GLS, LV GWI, LV GCW are independently associated with all-cause mortality. Among these parameters, LV GWI yielded the highest prognostic value.

Non-invasive assessment of left ventricular hemodynamic forces in hypertrophic cardiomyopathy

Abstract Background Hemodynamic force (HDF) analysis allows non-invasive measurement of intraventricular pressure gradients, portraying cyclic spatial-temporal interaction between blood and tissues. Impaired HDFs have been implicated in early detecting of adverse cardiac remodelling and treatment response in various cardiovascular disorders, providing insights into cardiac physiology not offered by traditional cardiovascular imaging (1). Mainly explored in heart failure, HDF analysis has not been previously applied to hypertrophic cardiomyopathy (HCM). Purpose To investigate differences in systo-diastolic function in HCM patients compared to healthy controls using HDF analysis. Methods Forty patients with HCM diagnosis (20 obstructive and 20 non-obstructive) were retrospectively evaluated in comparison with 22 healthy controls. Left ventricular (LV) HDFs were derived from routine transthoracic apical 4-, 2- and 3-chamber views using a dedicated software. Apical-basal HDF curves were generated, where positive deflections represent forces directed from the LV apex to the base, whilst negative ones are directed toward the apex. Amplitude and timing parameters were derived, the latter indexed to total cardiac cycle duration. Results Table 1 shows the demographic, clinical and echocardiographic characteristics of HCM compared to controls. Patients with HCM were older, had a slower heart rate due to treatment with beta-blockers, and showed hypercontractility, as expressed by higher LV ejection fraction. Compared to controls, HCM patients showed reduced LV longitudinal force, i.e. the force during the whole cardiac cycle (4.17% [2.36-5.52] vs. 6.01% [4.73-7.78], p=0.002), shorter time interval to systolic peak (0.15 [0.12-0.16] vs. 0.19 [0.17-0.20], p <0.001), and shorter duration of LV impulse (0.29 [0.27-0.32] vs. 0.34 [0.32-0.37], p <0.001) (Figure 1). However, no differences in terms of systolic force peak (p=0.283) or LV impulse intensity (p=0.689) were detected. During the transition between systole and diastole, LV suction (i.e. the interval including late systolic deceleration and early diastolic suction) was significantly longer (0.26 [0.22-0.29] vs. 0.23 [0.21-0.25], p=0.023) but less pronounced (6.30% [4.56-8.44] vs. 8.72% [6.71-12.59], p=0.005), likely reflecting a relaxation impairment from the very beginning of diastole. Such impairment was maintained during early diastolic filling, where the amplitude of the positive deceleration flow force was severely reduced in HCM compared to controls (2.98% [1.98-4.58] vs. 7.11% [4.55-8.72], p <0.001). Conclusions HDF analysis in HCM patients revealed unique systolic and diastolic changes reflecting faster LV contraction during systole and slower and weaker LV forces during diastole. This analysis deepens our understanding of HCM mechanic abnormalities and may help assess response to innovative treatment options.

Natural progression of rheumatic aortic valve disease following rheumatic mitral valve intervention: 16-year single center experience

Abstract Backgrounds and Objectives Recognizing the natural progression of the aortic valve (AV) disease is helpful in planning the intervention of significant rheumatic mitral valve (MV) disease accompanying rheumatic AV disease. We aimed to investigate the long-term course of AV disease and the need for AV surgery in patients with rheumatic mitral valve disease who underwent MV intervention. Methods We retrospectively investigated the progression of AV disease with rheumatic changes following MV intervention in a single tertiary center. A total of 890 patients who underwent MV intervention for rheumatic MS or mitral regurgitation (MR) without concurrent AV intervention were initially screened for eligibility. Among them, 76 patients met the criteria for rheumatic etiology and had over a year of echocardiographic follow-up after MV intervention (64 surgery, 12 balloon valvuloplasty). Results The median follow-up period was 4 years (mean 5.8 years, ranging from 1 to 31 years). MS was the most common indication for mitral intervention. Overall, trans-aortic peak velocity (AV Vmax) changed from 2.2 ± 0.6 m/s to 2.4 ± 0.8 m/s, and mean pressure gradient (mean PG) changed from 11.1 ± 6.0 mmHg to 13.2 ± 8.2 mmHg. Six patients fell under severe aortic stenosis (AS) definition-wisely (Figure 1) and three of them were classified as low flow low gradient severe AS despite normal ejection fraction. Eventually, four patients were found to have true-severe AS and only one of them underwent AV surgery for severe AS per se. None of the patients with aortic regurgitation deteriorated to severe (Figure 2). Conclusions Only a small portion of rheumatic AV involvement progresses to severe AS after MV intervention, and performing MV intervention for severe mitral stenosis or mitral regurgitation in patients with concurrent mild or moderate AS or aortic regurgitation due to rheumatic changes might be reasonable.The changes in the grading of ASThe changes in the grading of AR

Interventional treatment of patients with hypertrophic obstructive cardiomyopathy: the immediate and long-term results

Abstract Background Alcohol septal ablation (ASA) is a widely accepted and effective procedure for reducing septal thickness in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM) who do not respond to medical treatment and have significant outflow tract gradients. Despite numerous studies confirming its safety and efficacy, as well as current guidelines from 2020 recommending ASA as a class 1 treatment option alongside surgical myectomy[1], the decision between these methods is still a subject of debate. Methods From 2009 to 2022 154 ASA performed in 145 patients (91 males, 54 females) with HOCM at our centre. Mean age of pts. was 42 [6;77] years. All pts. had right ventricle pacing lead with pacemaker backup and myocardial contrast ECHO(MCE) before procedure. Mean peak pressure gradient (PG) on LVOT was 93,5 ± 8,2 mm. Hg. Mitral valve regurgitation (MR) from moderate to severe was in all pts. Mean interventricular septum thickness was 2,5сm [1,6; 3,8]. Results Mean PG on LVOT decreased from 93,5 ± 8,2 mmHg to 31,7±4,3 mmHg. The grade of MR reduced from at least moderate to mild or even trivial. The procedure – related mortality was 1,3%. In 3 cases (2%) the procedure was aborted by he MCE data. Mean follow up for 145pts (100%)was 91±4,6 months. 112(77,3%) pts had PG reduction (to ≤30 mtmHg) – regarded as good result of procedure. 19 (13,1%) pts had PG > 30mmHg, but significant improvement in symptoms. Long term mortality in ASA pts. was 2.7%. 10(6.9%) pts needed redo procedure due to residual LVOTO, which was effective. 13(8,9%) patients had complete AV block and required permanent pacemaker. Mean interventricular wall thickness decreased from 2,5±0,3сm to 1,8±0,2cm. MR decreased from at least moderate to mild or complete disappearance. NYHA class reduced from 2,9 to 1,2. Conclusions ASA is effective and safe method of HOCM treatment. Accumulation of the experience can lead to a reduction in procedure time, a decrease in the number of complications, and an overall improvement in the outcomes of interventional HOCM treatment.

Calculation of intraprocedural hemodynamics with computational functional dynamic in mitral valve edge-to-edge repair

Abstract Background Hemodynamic outcomes in patients undergoing transcatheter edge-to-edge-repair of the mitral valve (M-TEER) are difficult to predict. Computational functional dynamic (CFD) is frequently used in biomedical engineering to simulate blood flow patterns under various conditions. The authors developed a standardized workflow for individualized analyses and investigated the hemodynamic of mitral regurgitation volumes and gradients by using CFD. Methods 20 patients from two high volume centers who suffered from severe mitral regurgitation (MR) and underwent full cycle cardiac computed tomography (CT) prior procedure were enrolled. Baseline computed tomography and intraprocedural data were analyzed. Based on the specific valve morphology, individualized CFD-simulations were performed to calculate MR volumes prior to intervention and estimate hemodynamics after M-TEER. Results CFD-analyses of 20 patients (mean age 80±4 years, 60% male) showed excellent correlation between baseline PISA method-based MR volumes (45±23ml) measured in transesophageal echocardiography (TEE) and CFD-based calculation (45±26ml; R=0.917; P<0.001) as well as between TEE-measured mean baseline effective regurgitant orifice area (EROA; 27±16mm²) and CFD-measured EROA (24±18mm²; R=0.869; P<0.001)). After device implantation, correlation between intraprocedural TEE-measured and CFD-estimated correlation for residual MR volumes (R=0.949; P<0.001) and EROA (R=0.841; P<0.001) remained robust. Post-interventional mean diastolic pressure gradient (TEE) was 3.6±2.8mmHg which was in close correlation with the CFD estimated gradient (3.0±1.8mmHg, R=0.905; P<0.001). Conclusions This is the first study to use a CFD-standardized workflow for predicting hemodynamic changes in patients undergoing M-TEER using data from two different centers. In the future, CFD-based analyses might serve as a key-diagnostic tool for predicting residual MR volumes and gradients for M-TEER-procedures.Comparison of TEE and CFD flow patternBland-Altman-Blots

Transpulmonary proteome gradients identify inflammatory pathways involved in the development of pulmonary vasculopathy in heart failure

Abstract Background Some, but not all, patients with heart failure (HF) develop pulmonary vascular disease (PVD), which contributes to poor prognosis. Mechanisms leading to PVD in HF are poorly understood. Unbiased analysis of transpulmonary gradients may identify not only markers but also mediators of PVD by identifying proteins that may be consumed or elaborated across the lungs. Purpose Examine hemodynamics and transpulmonary proteome gradients in HFrEF and controls. Methods 21 non-HF controls and 160 patients with advanced HFrEF underwent pulmonary artery (PA) catheterization with blood sampling from the PA catheter in the wedged position (02sat > 90%, indicating pulmonary venous blood) and the un-wedged position to obtain transpulmonary proteome gradients. Samples from controls and HF from the highest quartile (Q4, n=40) and lowest quartile (Q1, n=40) of pulmonary vascular resistance (PVR) were analyzed using proteomic PEA assay of 275 proteins (Olink Target 96, panels CVII, CVIII, Inflammation). Pulmonary artery concentrations ("markers") or transpulmonary fold-change gradients (i.e. putative "mediators") of normalized protein expression (NPX) were plotted against significance; Benjamini–Hochberg FDR<0.05 considered as significant. Results Patients displayed typical characteristics of HFrEF (age 56±8y, NYHA 3.0 ±0.6, 87% males, LVEF 24±9.6%), Controls had similar anthropometrics, gender and age. Comparing all HF to Con, 38 markers of HF were identified (NPX fold-change>2), including 33 up (top 5: NTproBNP, BNP, GDF15, FGF23, IL8) and 5 down. HF patients in Q1 had median PVR 1.5 (IQR: 0.3-1.7) WU and those in Q4 had PVR 5.4 (4.3-6.6) WU. Comparison of Q1 and Q4 identified 3 protein markers of high PVR in PA blood from HF: chemokine CCL3, TNFRSF13B and surfactant protein-D (PSP-D). Examination of protein gradients from HF lungs (Figure) showed significant uptake of 14 protein mediators, most of which were associated with inflammatory responses (top 5: OSM, MMP9, CCL19, BNP, TR), and release of 8 mediators (top 4: IL-6, IL33, CCL4, CXCL10). In contrast, protein gradients were negligible in controls. Patients in Q4 PVR group were characterized by the highest pulmonary uptake of OSM (Oncostatin-M), lymphatic chemokine CCL19, BNP, MMP9, and had more significant transpulmonary release of IL6 and IL33. Across all patients, OSM lung uptake was the strongest correlate of transpulmonary pressure gradient (r=-0.3, p<0.001). Conclusions Lungs of patients with HF, and particularly those with high PVR, display abnormal uptake and release of proinflammatory CC and CXC chemokines and cytokines from IL1 and IL6 family, along with increased pulmonary uptake of IL6-type cytokine Oncostatin-M, a known mediator of lung inflammation and fibrosis, that acts via gp130/JAK/STAT, suggesting a novel role in PVD due to HF.Transpulmonary proteome in HF patients

Cardiac amyloidosis Echo-Score for patients with severe aortic stenosis. The AMY-TAVI trial

Abstract Background and Purpose A longitudinal strain pattern characterized by apical sparing (RELAPS>1) has been identified as indicative of cardiac amyloidosis (CA). We conducted an analysis to assess its diagnostic accuracy in individuals with severe aortic stenosis (AS) and explored novel echocardiographic variables for predictive value. Methods All patients diagnosed with AS who underwent transcatheter aortic valve implantation (TAVI) were prospectively enrolled. 2D-Speckle-tracking echocardiography was utilized to assess myocardial deformation parameters. Subsequent to TAVI, screening for CA was conducted through 99mTc-DPD scintigraphy and protein electrophoresis. Results A total of 324 patients were included (mean age 81.5 ± 5.8 years, 51% women). Among them, 38 individuals (11.7%) exhibited cardiac uptake in scintigraphy: 14 patients (4.3%) with grade 1, 13(4%) grade 2, and 11(3.4%) grade 3. RELAPS>1 was more prevalent in patients with AS-CA (74%vs.44%,p=0.006). We propose an echocardiographic prediction model (GRAM score) for CA in the context of AS that is more sensitive and specific than RELAPS >1 alone. This model incorporates the left ventricular mass index, maximum transvalvular aortic pressure gradient, RELAPS>1, and age (AUC: 0.85, 95% CI: 0.77–0.93). Conclusions While RELAPS >1 is more commonly observed in individuals with AS-CA, it is noteworthy that this pattern can also manifest in nearly half of AS patients without CA, diminishing its utility as a standalone screening tool. In light of this, our study puts forth a more sensitive and specific prediction score for identifying CA in patients with severe AS.GRAM score for predicting AS-CA

Impact of SAPIEN3 Ultra RESILIA on improvement of valve performance: Insights from the multicenter registry: a propensity-score matched analysis

Abstract Backgrounds: Transcatheter aortic valve implantation (TAVI) is now a cornerstone treatment for symptomatic severe aortic stenosis across all risk profiles, including low-risk and younger patients. As such, the performance and durability of transcatheter heart valves (THVs) are paramount. SAPIEN3 Ultra RESILIA (S3 UR) is expected to improve hemodynamics compared with SAPIEN3 (S3) due to the use of RESILIA bovine pericardial tissue and modified sawing maneuvers for each of three leaflets in 20 and 23mm valves. Aim The aim of study was to evaluate the hemodynamic improvement with S3 UR compared to S3 who underwent TAVI. Methods In a multicenter TAVI registry, we identified 1,931 patients who received a balloon-expandable valve over the past three years. We focused on post-procedural effective orifice area (EOA), post-procedural indexed EOA (EOAi), incidence of prosthesis-patient mismatch (PPM), paravalvular leakage (PVL) and post-procedural mean pressure gradient (mean PG) as our primary endpoints. We preformed propensity score matching analysis using a 1:1 ratio. Parameters including aortic stenosis severity, % oversizing and post dilatation were incorporated into the matching model. Results Of patients, mean age was 84 years old and 37.9% were male. EOAi was significantly larger in S3 UR group than in the S3 group for both cohorts [overall cohort: 1.21 (1.02 – 1.36) vs. 1.08 (0.93 – 1.26), P = 0.001; propensity matched cohort: 1.21 (1.01 – 1.35) vs. 1.11 (0.91 – 1.27), p = 0.042, respectively] (Figure 1). Similarly, the degree of PVL was significantly less in the S3 UR group than in the S3 group for both cohorts. In the propensity matched cohort, mild PVL was identified in 6.5% vs. 14.7%, and moderate PVL was present in 0.0% vs. 1.6% (p = 0.028). Peak PG and mean PG were significantly lower in the S3 UR group than in the S3 group for both cohorts. In the propensity matched cohort, peak PG was 17.7 (14.3 – 24.5) vs. 23.2 (18.2 – 29.2) (p = 0.001) and mean PG was 9.0 (7.1 – 12.5) vs. 11.5 (8.9 -14.8) (p = 0.005), respectively. The incidence of PVL ≥ mild, mean PG ≥ 20 mmHg, moderate PPM and severe PPM were tend to be lower in S3 UR group than in the S3 group for both cohorts (Figure 2). Conclusion The S3 UR valve exhibits significant hemodynamic improvements compared to the S3 valve, underscoring its potential for improved clinical outcomes in TAVI patients.

Endo-hepatology: Why should we do endoscopic ultrasound-guided interventions to the liver that we could do through the skin?

Endoscopic ultrasound (EUS)-guided interventions on the liver such as diffuse biopsy and portal pressure gradient measurement are emerging as potential alternatives to percutaneous procedures. The purpose of this editorial was to address all the indications that could potentially make an EUS-guided approach a possible alternative to the percutaneous procedures with respect to the proce-dures that could join the EUS examination such as upper endoscopy for gastro-esophageal varices, pancreaticobiliary investigation with EUS, and other potential advantages in terms of patient safety. The issue of a holistic gastroenterologist approach was also discussed along with the potential for developing clinical research.

PRIORiTize-TAVI might predict more than transcatheter aortic valve replacement waiting list priorities

Abstract Background PRIORiTize-TAVI (Predicting moRtalIty Or uRgent TAVI on waiting list) is a novel scoring system targeting identification of patients at risk of urgent hospitalization or death whilst waiting for transcatheter aortic valve replacement (TAVR) (1). Patients are divided into those with low (<2 points), intermediate (3-4 points) and high (>5) waiting risk. Given the novelty of the score, additional research is required to further validate it. However, being compiled of parameters applied in everyday practice that are readily available, the application of the score might have the potential to go beyond its original purpose. Purpose We aimed to investigate whether PRIORiTize-TAVI score can predict postprocedural complications and survival following TAVR. Methods We conducted a registry-based study including patients who underwent TAVR at our institution from 2018 to 2023. PRIORiTize-TAVI was calculated summarizing points according to NYHA status, left ventricular ejection fraction (LVEF), NTproBNP, mean pressure gradient (meanPG) and Charlson comorbidity index (CCI) at the time of patient placement onto TAVR waiting list. Results This registry-based study included 252 patients with median age 80 (interquartile range (IQR) 76-84) years, 50% female. Median PRIORiTize score was 5 (IQR 3-7). There were 41 (16%) low, 51 (20%) intermediate and 160 (64%) high risk patients. High risk patients had more frequently atrial fibrillation and ischaemic stroke, had lower LVEF and estimated glomerular filtration rate (eGFR), higher NTproBNP levels and CCI (Table 1). MeanPG also statistically differed between intermediate risk group and low risk group, but not with high risk group (Table 1). TAVR waiting time was significantly shorter in high-risk patients in comparison to intermediate risk patients. There was no statistical difference regarding baseline characteristics between the three groups (Table 1). There was no statistical difference in post-TAVR complications between the three groups. Survival significantly differed depending on PRIORiTize risk stratification (P=.023), as shown in Figure 1. Median survival time for high risk patients was 49 months (IQR 42-49), whereas the median survival time for intermediate and low risk patients could not be reached. High risk patients had lower survival probability compared to both intermediate (HR 4.089; CI 1.91-8.73) and low risk (HR 2.078; CI 0.77-5.59) patients. Intermediate risk patients had a higher survival probability compared to low risk patients (HR 0.508; CI 1.67-1.54). Length of TAVR waiting time had no significant association with overall survival (P=.891). Conclusions Our data show that PRIORiTize-TAVI has a potential to be used as a prognostic tool to predict survival probability post-TAVR. Our results suggest that prolonged time on TAVR waiting list did not negatively impact patient postprocedural complications nor survival.Table 1Figure 1

Transcatheter aortic valve replacement with balloon-expandable and self-expandable valves in Japanese patients with large annulus: the OCEAN-TAVI registry

Abstract Background East Asians have smaller aortic valve complexes than individuals from Western countries, and few studies have reported transcatheter aortic valve replacement (TAVR) outcomes in Asian patients with a large annulus. Purpose We aimed to compare the acute and long-term outcomes of TAVR using balloon-expandable valves (BEVs) and self-expandable valves (SEVs) in Asian patients with a large annulus. Methods We retrospectively analyzed the data from the Optimized transCathEter vAlvular interveNtion Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry. A large annulus was defined by annular area ≥ 500 mm2 and average diameter ≥ 25 mm in computed tomography scans. The primary endpoint was the 3-year all-cause mortality. Secondary endpoints were 3-year heart-failure rehospitalization (HFR) after TAVR, acute outcomes of TAVR, and changes in valve function on echocardiography 2 years after TAVR. Results Among 773 patients, 671 (86.8%) underwent BEV-TAVR. The SEV-TAVR group showed a significantly higher incidence of above-moderate perivalvular leakage (2.1% vs. 7.8%; P < 0.001), and included a significantly greater percentage of patients who required postoperative pacemaker implantation (6.1% vs. 11.8%; P = 0.035). The incidence of moderate-to-severe prosthesis–patient mismatch did not differ between the two groups. The Kaplan–Meier curve showed no significant intergroup differences in the 3-year all-cause mortality and HFR rates (log-rank P = 0.900), and the echocardiography-indexed effective orifice area and mean transaortic valve pressure gradient at 2 years post-TAVR did not differ significantly between the two groups. Conclusions The benefits of BEV-TAVR may outweigh those of SEV-TAVR in patients with a large annulus.

Interleukin-22 inhibits right ventricular remodelling by a unique mechanism in a pulmonary artery constriction model

Abstract Background Fibrosis and remodeling of right ventricle (RV) are associated with prognosis in patients with RV failure. Interleukin-22 (IL-22) is a member of the IL-10 cytokine family, play roles in tissue protection and wound repair. We have previously shown that IL-22 plays an important role in cardiac remodeling after acute myocardial infarction; however, the role of IL-22 in RV fibrosis and remodeling remains elusive. Purpose We investigated the role of IL-22 in the pathogenesis of RV remodeling during pressure overload. Methods Pulmonary artery banding (PAB) is performed by placing a 6-0 suture around the pulmonary artery over a 24 G needle in wild type mice (C57BL/6J) and IL-22 knockout mice (IL-22 KO). Only mice with moderate pulmonary artery stenosis (peak pressure gradient across the pulmonary band: 25–40 mmHg at 1 week after surgery by echo Doppler) were included in the study protocol. Four weeks after PAB, RV function was measured by echocardiography and real-time PCR analysis was performed to measure Col1a1, Col3a1, BNP, and transcriptome analysis was performed. Survival confirmation of mice with moderate pulmonary artery stenosis was also performed up to 56 days. Results IL-22 KO mice had significantly higher 56-day mortality rate compared with WT mice after PAC (p<0.01). Four weeks after PAB, IL-22 KO mice showed markedly increased RV weight (IL-22 KO mice vs. wild-type mice; RV/LV+IVS: 0.48±0.05 vs 0.40±0.02, P=0.002). IL-22 KO mice exhibited significant RV enlargement and RV dysfunction 4 weeks after PAB. (IL-22 KO mice vs wild type mice; RVEDV: 10±2.3mm2 vs 12.9±3.1mm2, P=0.005, TAPSE: 10.8±1.8mm vs 9.5±1.7mm, P=0.04, FAC: 35.2±7.8% vs 23±6.0%, P<0.001). The expressions of Col1a1 and Col3a1 were no difference between in IL22-KO mice and Wild mice. However, BNP, a cardioprotective marker, tended to be lower in IL-22KO mice. The transcriptome analysis also showed that the group of fibrosis-related genes that are elevated in PAC in WT mice were less elevated in IL-22 KO mice. Conclusion These results suggest that IL-22 is involved in RV remodelling during RV pressure loading without a general mechanism.

Prognostic impact of echocardiographic predictors of subclinical systolic dysfunction in patients with moderate aortic stenosis

Abstract Introduction Moderate aortic stenosis (AS) marks a critical point in AS severity spectrum, paralleled by significant cardiac structural changes. Concentric left ventricular (LV) hypertrophy, in response to the increased afterload, enables the preservation of a normal ejection fraction (EF) despite significant underlying myocardial dysfunction. Reductions in LVEF may serve as early indicators of the LV's diminished capacity to withstand this increased afterload, potentially leading to LV fibrosis and irreversible myocardial damage. Research has shown that LVEF may not recover in some patients following aortic valve replacement (AVR). Consequently, there is a growing debate concerning higher LVEF thresholds for triggering AVR in patients with severe AS, aiming to intervene before clinical systolic dysfunction ensues and irreversible damage occurs. Meanwhile, a combination of objective indicators may help to identify those patients AS at high risk before a decline in LVEF occurs. Aim To explore the role of baseline left ventricle global longitudinal strain (GLS) and strain rate (SR) as markers of subclinical LV dysfunction, as predictors of LVEF depression, and their impact on survival of patients with moderate AS. Methods Patients with moderate AS and LVEF ≥ 50% at least in 2 echocardiograms were retrospectively identified. Prosthetic and bicuspid valves were excluded. Baseline LV GLS and SR were used as covariates in cox regression models to predict the cumulative incidence of LVEF depression over 5 years and overall survival after multivariable adjustment including time-dependent AVR. Results 574 patients were included (age 76 ± 9 years; 51% female; median follow-up time of 8.97 years). The average baseline aortic peak velocity was 3.4±0.8 m/s, mean pressure gradient was 25±9 mmHg, aortic valve area was 1.1± 0.3 cm2, and LVEF 60±5%. The average GLS was -17±7 % while the peak systolic SR was 1.2 ± 0.5/s. Both baseline GLS (HR= 0.88 for each -1%; 95% CI= 079-0.99; p= 0.04) and SR (HR= 0.89 for each +0.1/s; 95% CI= 0.80-0.99; p=0.03) were associated with 5-year incidence of LVEF depression (<50%). Risk discrimination improved by incorporating SR on top of GLS (increase in area under curve from 0.78 to 0.84; 95% CI= 0.01-0.10; p= 0.04). Furthermore, a nonlinear relation was found between GLS (optimal boundary <-15.8%; p=0.35) and SR (optimal boundary >0.96/s; p=0.34) and overall survival. Conclusions This study identifies baseline GLS and SR as predictors of LVEF depression in moderate AS underscoring their importance in detecting subclinical LV dysfunction. The combination of GLS and SR may enhance the prediction of cardiac function decline, suggesting their potential utility in guiding early intervention strategies. Although their direct relationship with survival needs further exploration, these findings advocate for incorporating GLS and SR in AS management to inform timely AVR decisions and improve patient outcomes.

Intracoronary nicardipine to induce hypaeremia

Abstract Background Several pharmacological agents and routes of administration have been used to induce transient maximal hyperaemia, but most suffer from shortcomings that limit their clinical usage. Nicardipine, a dihydropyridine calcium channel blocker, has been proposed as a coronary hyperaemic agent with the advantage of not causing any adverse effects. Purpose We compared intracoronary (IC) nicardipine with IC papaverine for obtaining fractional flow reserve (FFR) and pullback pressure gradient (PPG). Methods and results This is a prospective, single-center study enrolling stable patients presenting with intermediate coronary artery disease (CAD) undergoing invasive functional assessment. The lowest FFR, duration of the hyperemic plateau, and PPG were assessed after IC nicardipine (400 µg to the left coronary or 300 µg to the right coronary artery) and IC papaverine (12 mg to the left coronary artery and 8 mg to the right coronary artery). Results Overall, 107 patients with 108 vessels (216 FFR and 216 PPG paired measurements) were analyzed. The correlation in FFR between nicardipine and papaverine was r = 0.95 (95% CI 0.92 to 0.96, p < 0.001) with a mean difference of 0.02 FFR units (limit of the agreement [LOA]: -0.04 to 0.08). Similarly, the correlation in PPG between nicardipine and papaverine was r = 0.86 (95% CI 0.71 to 0.93, p < 0.001) with a mean difference of 0.01 PPG units (limit of the agreement [LOA]: -0.14 to 0.17). The hyperaemic plateau was significantly longer with nicardipine (101.4 ± 62.1 s nicardipine vs 41.5 ± 14.3 s papaverine, p < 0.001). No significant differences were observed in the magnitude of changes in blood pressure and heart rate (p=NS). No complications occurred with the administration of IC nicardipine or papaverine. Conclusion FFR and PPG values obtained following nicardipine administration exhibited excellent agreement with those obtained using papaverine. Moreover, the hyperaemic response induced by nicardipine led to a significantly prolonged steady state in comparison to papaverine. Given its widespread availability, cost-effectiveness, safety profile and frequent utilization in clinical settings, nicardipine emerges as the optimal vasodilator for coronary physiology testing.FFR by Nicardipine vs PapaverinePPG by Nicardipine vs Papaverine

Comparison of the effects of pre-dilatation with conventional versus larger balloon sizes on clinical outcomes in transcatheter aortic valve implantation with self-expandable valves

Abstract Background Transcatheter aortic valve implantation (TAVI) is considered an established treatment option for patients with severe aortic stenosis. When implanting self-expandable valve, pre-dilatation is often necessary to facilitate optimal transcatheter heart valve (THV) deployment. Traditionally, balloon sizes chosen for pre-dilatation are smaller than the minimum annulus diameter. Insufficient pre-dilatation can result in under-expansion of the THV, necessitating post-dilatation, and can increase the risk of complications. However, this conventional approach may not always yield the best outcomes, prompting a reassessment of balloon sizing strategies to improve procedural success and patient outcomes. Purpose The aim of this study was to investigate the impact on procedural outcomes of using larger balloons, sized less than the mean annulus diameter, for pre-dilatation compared to the traditional practice of using balloons sized less than the minimum annulus diameter during the implantation of self-expandable valves. Methods We analyzed 785 patients who underwent TAVI with self-expandable valve with pre-dilatation out of a consecutive 3880 cases at 6 centers from 2010 to 2023 (Figure 1). Among them, we divided the patients into two groups: those who underwent pre-dilation with balloons smaller than the minimum annulus diameter defined as the Conventional-size group and those who underwent pre-dilatation with balloons smaller than the mean annulus diameter defined as the Large-size group. The primary endpoint of this study was procedural success, stroke and need for permanent pacemaker implantation as designated by the VARC-3criteria. Results Of patients (69% female; mean age 84.9), there were 563 (71.7%) patients in the Conventional-size group and 222 (28.2%) patients in the Large-size group. There was no annulus rupture in either group. The incidence of post-dilatation was significantly higher in the Conventional-size group than in the Large-size group (109 of 563 [19.4%] vs. 23 of 222 [10.3%], p=0.001) (Figure 2). There was no significant difference in the incidence of primary endpoints (all p > 0.05). In post-echocardiographic outcomes, there was no significant difference in effective orifice area, mean pressure gradient, patients-prosthesis mismatch, or paravalvular leakage between the groups (P > 0.05). Conclusions This study demonstrates that a large-size strategy using a balloon smaller than the mean annulus diameter in the deployment of self-expandable valves is safe and may avoid the need for post-dilatation compared to the traditional strategy using a balloon smaller than the smallest diameter.

Prevalence and outcomes of patients with discordant high gradient aortic stenosis

Abstract Background Conflicting prognostic results have been reported in patients with discordant high gradient aortic stenosis (DHG-AS, the combination of a mean pressure gradient ≥40 mmHg and an aortic valve area (AVA) >1cm² ). Moreover, existing studies only included selected patients without concomitant aortic regurgitation. Purpose We assessed the prevalence and survival of patients presenting with DHG-AS in an unselected group of consecutive patients presenting to the echocardiography laboratory of a tertiary referral center. Methods 3,547 adult patients with AVA ≤1.5cm² and peak aortic jet velocity ≥2.5m/s or mean gradient ≥25mmHg who presented between 2005 and 2015 were included. Baseline clinical and echocardiographic data, and, when available, aortic valve calcium score (AVC) were collected in an institutional database, with subsequent retrospective analysis. The primary endpoint was all cause mortality during follow-up. Results DHG-AS was observed in 163 patients (11.6% of all patients with a gradient ≥ 40mmHg). After adjustment for potential confounders, overall mortality rate of patients with DHG-AS was similar to that of concordant severe AS (AVA ≤1cm², mean gradient ≥40mmHg; CSev-AS) patients (N=1,243; HR: 0.98[0.68;-1.44]; p=0.91), and discordant low gradient-AS (AVA ≤1cm²; gradient <40 mmHg; HGDLG-AS) patients (N=1,131, HR: 0.85[0.58-1.26]; p=0.42), and was worse than that of concordant moderate AS (AVA >1.0cm², gradient <40mmHg; CMod-AS) patients (N=1,010; HR: 0.54[0.36-0.81]; p=0.003, Fig 1). After adjustment for aortic velocities, aortic regurgitation had no significant impact on survival. Calcium scoring was performed in 716 patients, including 40 patients with DHG-AS. AVC in DHG-AS was higher than in patients with CMod-AS and DLG-AS, and not significantly different from that of CSev-AS. The AVC ratio (AVC divided by the sex-specific thresholds) was higher in patients with DHG-AS as compared to both CMod-AS and DLG-AS patients (Fig 2). Conclusions DHG-AS is not uncommon. Although an AVA ≥1.0 cm² is often seen as reassuring and mistaken as moderate AS, a high-pressure gradient conveys a poor prognosis, whatever the AVA and independently of the presence of concomitant aortic regurgitation.

Interleukin 6 in asymptomatic patients with nonsevere aortic valve stenosis: a post-hoc study of the SEAS trial

Abstract Background Inflammation plays a pivotal role in the pathogenesis of aortic valve stenosis (AS) through cytokine-mediated valve calcification. Studies of explanted valves found associations of an elevated pro-inflammatory cytokine, Interleukin 6 (IL-6), with increased postoperative mortality. However, limited knowledge exists regarding the prognostic value of elevated circulating IL-6 in asymptomatic patients with nonsevere AS. Purpose To investigate the hypothesis that elevated plasma IL-6 concentration ≥7 pg/mL (above the upper limit of normal 95th percentile) correlates with more severe AS and a higher risk of adverse outcomes in asymptomatic patients with nonsevere AS. Methods We analyzed data of 1574 asymptomatic patients who had mild-to-moderate AS, preserved systolic and kidney function, no overt cardiovascular diseases, and an event-free follow-up one year after enrollment in the randomized Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. We ascertained the correlation of year-0 and year-1 IL-6 levels with echocardiographic AS severity, defined as moderate-severe AS in the presence of ≥2 measurements at year-0: aortic valve area <1 cm², mean pressure gradient ≥40 mmHg, maximal transaortic velocity ≥4 m/s, and velocity ratio <0.25. Multivariable regression examined correlations between IL-6 at year-0 and clinical variables. Cox proportional hazard models and competing risk analyses examined associations of elevated IL-6 at year-1 and 4-year risk of the primary composite endpoint of major cardiovascular events (MACE) comprising the first event of cardiovascular death, aortic valve replacement, hospitalization with heart failure, myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or ischemic stroke. Results At year-0, among 1574 patients with a mean (SD) age of 67.5 (9.7) years, 629 (40.0%) were women, 263 (16.7%) had moderate-severe AS, and 194 (12.3%) had elevated IL-6. The median relative IL-6 change from year-0 to year-1 was 1.0 (IQR, 0.8-1.4) across AS-severity groups (P=0.12) (Figure 1). In adjusted models, IL-6 at year-0 did not correlate with AS-severity (P=0.30). In mild AS, an elevated IL-6 at year-1 was associated with an increased 4-year MACE risk (HR 1.40; 95% CI, 1.02-1.92; p=0.04) in adjusted Cox regression analyses (Figure 2A). In sensitivity analyses, the annual IL-6 increase >50% combined with normal IL-6 was associated with an increased 4-year MACE-risk of HR 1.48 (95% CI, 1.10-2.00; P=0.009) in patients with mild AS and 1.82 (95% CI, 0.68-1.74; P=0.73) in patients with moderate-severe AS (all P for interaction>0.25) (Figure 2C-D). Conclusion In asymptomatic patients with nonsevere AS, circulating IL-6 remains stable within the reference range in 7 out of 8 patients during a 1-year follow-up, regardless of AS severity. An elevated IL-6 was associated with a 1.4-fold increased 4-year MACE-risk in patients with mild AS, suggesting its possible role as an early risk marker.Figure 1Figure 2