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Background: Tricuspid valve transcatheter edge-to-edge repair has emerged as a valuable treatment option for patients with severe tricuspid regurgitation (TR)., Objectives: This study aims to investigate the safety and effectiveness of the PASCAL transcatheter valve repair system in treating severe TR in a real-world patient population., Methods: The PASTE (PASCAL for Tricuspid Regurgitation-a European registry) study is an investigator-initiated, multicenter, retrospective, and prospective observational cohort analysis conducted across 16 European heart valve centers including consecutive patients treated with the PASCAL transcatheter valve repair system from February 2019 to November 2023. Echocardiographic assessments were performed at baseline, discharge, and follow-up, and were subjected to centralized analysis., Results: The study included 1,059 high-risk patients (mean age 79 ± 9 years; 53% female; TRI-SCORE risk 23% ± 18%; 87% NYHA functional class III/IV) with multiple comorbidities. Severe or higher graded TR was observed in 96% of patients. Intraprocedural success according to Tricuspid Valve Academic Research Consortium criteria was achieved in 85%, and TR reduced to ≤moderate in 87%. Independent predictors for a postprocedure residual TR of >moderate were coaptation gaps ≥8 mm (OR: 1.67; 95% CI: 1.03-2.72; P = 0.038), tenting height ≥10 mm (OR: 2.18; CI: 1.30-3.65; P = 0.003), the presence of a transvalvular lead (OR: 1.91; 95% CI: 1.19-3.05; P = 0.007), right ventricular dilatation >42 mm (OR: 3.35; 95% CI: 1.37-9.1; P = 0.009) and massive/torrential TR at baseline (OR: 4.59; 95% CI: 2.35-8.96; P < 0.001). At 1 year, 83% of patients showed ≤moderate TR. Significant clinical improvements included enhanced NYHA functional class (66% class I/II vs 17% at baseline; P < 0.001). Patients treated with the first-generation PASCAL system (n = 570) and with the new PASCAL Precision system (n = 489) had similar clinical profiles and TR severity at baseline. However, the Precision cohort showed greater TR reduction to trace/mild (63% vs 49%; P < 0.001), shorter procedure times (median 93 minutes [Q1-Q3: 69-130 minutes] vs 120 minutes [Q1-Q3: 82-165 minutes]; P < 0.001), and higher clinical success rates according to the Tricuspid Valve Academic Research Consortium at 30 days and 1 year (87% vs 81% [P = 0.021] and 56% vs 50% [P = 0.044], respectively). Higher center experience (≥21 patients/year) resulted in higher intraprocedural and clinical success., Conclusions: The PASCAL system effectively treats severe TR in high-risk patients, offering sustained TR reduction and significant clinical improvements at 1-year follow-up. (PASCAL for Tricuspid Regurgitation-a European registry [PASTE]; NCT05328284)., Competing Interests: Funding Support and Author Disclosures Dr Wild has received speaker fees from Abbott Vascular and Edwards Lifesciences; and has received honoraria for consultancy from IPPMed. Dr Stolz has received speaker honoraria from Edwards Lifesciences. Dr Praz has received travel expenses from Abbott Vascular, Polares Medical, and Edwards Lifesciences. Dr Lüdike has received speaker fees from Edwards Lifesciences. Dr Rassaf has received speaker fees from AstraZeneca, Daiichi-Sankyo, Bayer, Novartis, and Abiomed outside the submitted work. Dr Lurz has received grants from Abbott Vascular, Edwards Lifesciences, and ReCor Medical. Dr Stocker has received speaker honoraria from Edwards Lifesciences; and has served as a consultant for Occlutech International. Dr Kalbacher has received personal fees from Abbott Vascular, Edwards Lifesciences, Medtronic Inc, and Pi-Cardia Ltd. Dr Westermann has received honoraria from Abiomed, Medtronic, and Edwards Lifesciences. Dr Hausleiter has received research support and speaker honoraria from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

Background: Activation of the immune system contributes to cardiovascular diseases. The role of human-specific long noncoding RNAs in cardioimmunology is poorly understood., Methods: Single-cell sequencing in peripheral blood mononuclear cells revealed a novel human-specific long noncoding RNA called HEAT4 (heart failure-associated transcript 4). HEAT4 expression was assessed in several in vitro and ex vivo models of immune cell activation, as well as in the blood of patients with heart failure (HF), acute myocardial infarction, or cardiogenic shock. The transcriptional regulation of HEAT4 was verified through cytokine treatment and single-cell sequencing. Loss-of-function and gain-of-function studies and multiple RNA-protein interaction assays uncovered a mechanistic role of HEAT4 in the monocyte anti-inflammatory gene program. HEAT4 expression and function was characterized in a vascular injury model in NOD.CB17-Prkdc scid/Rj mice., Results: HEAT4 expression was increased in the blood of patients with HF, acute myocardial infarction, or cardiogenic shock. HEAT4 levels distinguished patients with HF from people without HF and predicted all-cause mortality in a cohort of patients with HF over 7 years of follow-up. Monocytes, particularly anti-inflammatory CD16 + monocytes, which are increased in patients with HF, are the primary source of HEAT4 expression in the blood. HEAT4 is transcriptionally activated by treatment with anti-inflammatory interleukin-10. HEAT4 activates anti-inflammatory and inhibits proinflammatory gene expression. Increased HEAT4 levels result in a shift toward more CD16 + monocytes. HEAT4 binds to S100A9, causing a monocyte subtype switch, thereby reducing inflammation. As a result, HEAT4 improves endothelial barrier integrity during inflammation and promotes vascular healing after injury in mice., Conclusions: These results characterize a novel endogenous anti-inflammatory pathway that involves the conversion of monocyte subtypes into anti-inflammatory CD16 + monocytes. The data identify a novel function for the class of long noncoding RNAs by preventing protein secretion and suggest long noncoding RNAs as potential targets for interventions in the field of cardioimmunology., Competing Interests: None.

Background : Heart failure with preserved ejection fraction (HFpEF) is a widespread condition with significant morbidity and mortality. Its clinical heterogeneity may delay the diagnosis. Aim : To identify predictors of HFpEF-related hospitalizations in ambulatory patients presenting with elevated cardiovascular risk, suspected coronary artery diseases (CADs), and positive HFpEF screenings. Methods : Consecutive patients presenting with suspected CAD, enrolled in the observational LIFE-Heart study (2006-2014, NCT00497887), and meeting HFpEF criteria per the 2016 European Society of Cardiology (ESC) guidelines were categorized according to the presence of "overlapping conditions" potentially masking or contributing to their symptoms. Additional stratification using the H 2 FPEF score (<2: low risk, 2-5: intermediate risk, and ≥6 high risk) was performed. Follow-up for hospitalizations, reasons of hospitalization, and death spanned a median of 6 years. Results : Of 1054 patients (66 ± 10 years, 60% male, NT-pro-BNP 286, IQR 183-574 pg/mL), 53% had overlapping conditions, while 47% had "isolated HFpEF". The H 2 FPEF scores classified 23%, 57%, and 20% as low-, intermediate-, and high-risk, respectively, with consistent proportions across patients with and without overlapping conditions ( p = 0.91). During the follow-up observational phase, 54% were rehospitalized, 22% experienced heart failure (HF) rehospitalizations, and 11% of patients died. Multivariable logistic regression revealed a high-risk H 2 FPEF category as an independent predictor of HF rehospitalization in the overall cohort (odds ratio: 3.4, CI: 2.4-4.9, p < 0.01) as well as in patients with and without overlapping conditions. Furthermore, a H 2 FPEF score ≥ 6 was independently associated with higher mortality rates (hazard ratio: 1.8, CI: 1.2-2.6, p < 0.01) in the Cox regression analysis. Conclusions : Ambulatory patients presenting for suspected CAD and meeting HFpEF screening criteria face elevated risks for rehospitalizations over six years. Regardless of concomitant diagnoses, quantifying cardiac damage with the H 2 FPEF score helps in risk-stratifying patients for HF hospitalization and mortality.

Aims: The aim of this study was to assess the pathophysiological implications of severe tricuspid regurgitation (TR) in patients with heart failure with preserved ejection fraction (HFpEF) by using tricuspid transcatheter edge-to-edge repair (T-TEER) as a model of right ventricular (RV) volume overload relief., Methods and Results: This prospective interventional single arm trial (NCT04782908) included patients with invasively diagnosed HFpEF. The following parameters were prospectively assessed before and after T-TEER: left ventricular (LV) diastolic properties by invasive pressure-volume loop recordings; biventricular time-volume curves and function as well as septal curvature by cardiac magnetic resonance imaging; strain analyses for timing of septal motion. Overall, 20 patients (median age 78, interquartile range [IQR] 72-83 years, 65% female) were included. T-TEER reduced TR by a median of 2 (of 5) grades (IQR 2-1). T-TEER increased LV stroke volume and LV end-diastolic volume (LVEDV) (p < 0.001), without increasing LV end-diastolic pressure (LVEDP) (p = 0.094), consequently diastolic function improved with a reduction in LVEDP/LVEDV (p = 0.001) and a rightward shift of the end-diastolic pressure-volume relationship. The increase in LVEDV correlated with a decrease in RV end-diastolic volume (p < 0.001) and LV transmural pressure increased (p = 0.028). Secondary to a decrease in early RV filling, improvements in early LV filling were observed, correlating with an alleviation of leftwards bowing of the septum (p < 0.01, respectively)., Conclusion: Diastolic LV properties in patients with HFpEF and severe TR are importantly determined by ventricular interaction in the setting of RV volume overload. T-TEER reduces RV volume overload and improves biventricular interaction and physiology., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: While invasively determined congestion holds mechanistic and prognostic significance in acute heart failure (HF), its role in patients with tricuspid regurgitation (TR)-related right- heart failure (HF) undergoing transcatheter tricuspid valve intervention (TTVI) is less well established. A comprehensive understanding of congestion patterns might aid in procedural planning, risk stratification, and the identification of patients who may benefit from adjunctive therapies before undergoing TTVI. The aim of this study was to investigate the role of congestion patterns in patients with severe TR and its implications for TTVI., Methods and Results: Within a multicentre, international TTVI registry, 813 patients underwent right heart catheterization (RHC) prior to TTVI and were followed up to 24 months. The median age was 80 (interquartile range 76-83) years and 54% were women. Both mean right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were associated with 2-year mortality on Cox regression analyses with Youden index-derived cut-offs of 17 mmHg and 19 mmHg, respectively (p < 0.01 for all). However, RAP emerged as an independent predictor of outcomes following multivariable adjustments. Pre-interventionally, 42% of patients were classified as euvolaemic (RAP <17 mmHg, PCWP <19 mmHg), 23% as having left-sided congestion (RAP <17 mmHg, PCWP ≥19 mmHg), 8% as right-sided congestion (RAP ≥17 mmHg, PCWP <19 mmHg), and 27% as bilateral congestion (RAP ≥17 mmHg, PCWP ≥19 mmHg). Patients with right-sided or bilateral congestion had the lowest procedural success rates and shortest survival times. Congestion patterns allowed for discerning specific patient's physiology and specifying prognostic implications of right ventricular to pulmonary artery coupling surrogates., Conclusion: In this large cohort of invasively characterized patients undergoing TTVI, congestion patterns involving right-sided congestion were associated with low procedural success and higher mortality rates after TTVI. Whether pre-interventional reduction of right-sided congestion can improve outcomes after TTVI should be established in dedicated studies., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Heart failure with preserved ejection fraction (HFpEF) is frequently attributed etiologically to an underlying left ventricular (LV) diastolic dysfunction, although its pathophysiology is far more complex and can exhibit significant variations among patients. This review endeavours to systematically unravel the pathophysiological heterogeneity by illustrating diverse mechanisms leading to an impaired cardiac output reserve, a central and prevalent haemodynamic abnormality in HFpEF patients. Drawing on previously published findings from our research group, we propose a pathophysiology-guided phenotyping based on the presence of: (1) LV diastolic dysfunction, (2) LV systolic pathologies, (3) arterial stiffness, (4) atrial impairment, (5) right ventricular dysfunction, (6) tricuspid valve regurgitation, and (7) chronotopic incompetence. Tailored to each specific phenotype, we explore various potential treatment options such as antifibrotic medication, diuretics, renal denervation and more. Our conclusion underscores the pivotal role of cardiac output reserve as a key haemodynamic abnormality in HFpEF, emphasizing that by phenotyping patients according to its individual pathomechanisms, insights into personalized therapeutic approaches can be gleaned., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Arterial stiffening contributes to hemodynamic derangements in heart failure with preserved ejection fraction (HFpEF). We sought to investigate the impact of renal denervation on pulsatile left ventricular loading in patients with HFpEF and hypertensive patients without heart failure (control)., Methods: Patients underwent renal denervation for treatment of hypertension and were followed up at 3 months at a single center. A validated computer model of the arterial tree, noninvasive aortic flow curves, left ventricular volumes, and E/e' as inputs were used to determine key parameters of left ventricular vascular load., Results: In comparison to controls (n=30), patients with HFpEF (n=30) demonstrated lower total arterial compliance (mean difference, -0.41 [95% CI, -0.72 to -0.10] mL/mm Hg), higher impedance of the proximal aorta (Zc: 0.02; 0.01 to 0.04 mHg·s/mL), premature wave reflections (shorter backward wave transit time normalized to ejection time: -3.5; -6.5% to -0.5%), and higher wave reflection magnitude (reflection coefficient: 7.3; 2.8% to 11.9%). Overall, daytime systolic (-9.2; -12.2 to -6.2 mm Hg) and diastolic blood pressures (-5.9; -7.6 to -4.1 mm Hg) as well as blood pressure variability (-2.0; -3.0 to -0.9 mm Hg) decreased after renal denervation. In patients with HFpEF, total arterial compliance (0.42; 0.17 to 0.67 mL/mm Hg) and backward transit time normalized to ejection time (1.7; 0.4% to 3.0%) increased; Zc (-0.01; -0.02 to -0.01 mm Hg·s/mL) and reflection coefficient (-2.6; -5.0% to -0.3%) decreased after renal denervation. This was accompanied by a symptomatic improvement in patients with HFpEF., Conclusion: HFpEF is characterized by heightened aortic stiffness and unfavorable pulsatile left ventricular load. These abnormalities are partly normalized after renal denervation., Competing Interests: Disclosures Drs Fengler and Lurz are consultants to and have received institutional research grants from Medtronic and ReCor. The other authors have no conflicts of interest to disclose.

Background Short-term effects on mitral valve (MV) anatomy after transcatheter edge-to-edge repair using the PASCAL system remain unknown. Precise quantification might allow for an advanced analysis of predictors for mean transmitral gradients. Methods and Results Consecutive patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation using PASCAL or MitraClip systems were included. Quantification of short-term MV changes throughout the cardiac cycle was performed using peri-interventional 3-dimensional MV images. Predictors for mean transmitral gradients were identified in univariable and multivariable regression analysis. Long-term results were described during 1-year follow-up. A total of 100 patients undergoing transcatheter edge-to-edge repair using PASCAL (n=50) or MitraClip systems (n=50) were included. Significant reductions of anterior-posterior diameter, annular circumference, and area throughout the cardiac cycle were found in both cohorts ( P <0.05 for all). Anatomic MV orifice area remained larger in the PASCAL cohort in mid (2.8±1.0 versus 2.4±0.9 cm 2 ; P =0.049) and late diastole (2.7±1.1 versus 2.2±0.8 cm 2 ; P =0.036) compared with the MitraClip cohort. Besides a device-specific profile of independent predictor of mean transmitral gradients, reduction of middiastolic anatomic MV orifice area was identified as an independent predictor in both the PASCAL ( β =-0.410; P =0.001) and MitraClip cohorts ( β =-0.318; P =0.028). At follow-up, reduction of mitral regurgitation grade to mild or less was more durable in the PASCAL cohort (90% versus 72%; P =0.035). Conclusions PASCAL and MitraClip showed comparable short-term effects on MV geometry. However, PASCAL might better preserve MV function and demonstrated more durable mitral regurgitation reduction during follow-up. Identification of independent predictors for mean transmitral gradients might potentially help to guide device selection in the future.

BACKGROUND Renal denervation has proven its efficacy to lower blood pressure in comparison to sham treatment in recent randomized clinical trials. Although there is a large body of evidence for the durability and safety of radiofrequency-based renal denervation, there are a paucity of data for endovascular ultrasound-based renal denervation (uRDN). We aimed to assess the long-term efficacy and safety of uRDN in a single-center cohort of patients. METHODS AND RESULTS Data from 2 previous studies on uRDN were pooled. Ambulatory 24-hour blood pressure measurements were taken before as well as 3, 6, 12, and 24 months after treatment with uRDN. A total of 130 patients (mean age 63±9 years, 24% women) underwent uRDN. After 3, 6, 12, and 24 months, systolic mean 24-hour ambulatory blood pressure values were reduced by 10±12, 10±14, 8±15, and 10±15 mm Hg, respectively, when compared with baseline ( P <0.001). Corresponding diastolic values were reduced by 6±8, 6±8, 5±9, and 6±9 mm Hg, respectively ( P <0.001). Periprocedural adverse events occurred in 16 patients, and all recovered without sequelae. CONCLUSIONS In this single-center study, uRDN effectively lowered blood pressure up to 24 months after treatment.

Persisting iatrogenic atrial septal defects (iASD) after transcatheter mitral edge-to-edge repair (M-TEER) are associated with impaired outcomes. We investigated the natural history of relevant iASDs with left-to-right shunting post-M-TEER, predictors of spontaneous closure of iASD between 1 and 6 months post-M-TEER, and outcomes (heart failure [HF] hospitalization) in patients with spontaneous closure versus those with persistent iASD 6 months post-M-TEER. Patients with a relevant iASD 1-month post-M-TEER, who were treated conservatively in the randomized controlled MITHRAS trial, underwent clinical follow-up including transesophageal echocardiography 6 months post-M-TEER. Overall, 36 patients (median 77 [interquartile range 65-81] years; 36% women) completed the 6-months follow-up. Six (17%) patients had a spontaneous closure of the iASD. The eccentricity index of the iASD 1-month after M-TEER was the strongest predictor for spontaneous closure (Odds ratio 3.78; 95% confidence interval 1.26-11.33, p = 0.01) and an eccentricity index of < 1.9 provided a sensitivity of 77% at a specificity of 83% for iASD persistence (Area under the curve 0.83, p < 0.001) within 6-months post M-TEER.At follow-up, a numerical difference in the endpoint of HF hospitalization between the spontaneous closure and the residual shunt group (0% vs. 20%, p = 0.25) was observed. The eccentricity of the iASD was the strongest predictor for spontaneous closure at 1-months and an eccentricity index of < 1.9 is associated with a high persistence rate for 6 month after M-TEER. Clinical Trial Registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03024268 Identifier: NCT03024268. a (red) is reflecting the mayor lengthwise dimension and b (blue) the mayor oblique dimension. The eccentricity index is calculated by dividing a through b. (Open circle) is depicting an example for a round iASD and (Open rhombus) an example for an eccentric iASD 1 month after M-TEER., (© 2022. The Author(s).)

Background: Recent trial data suggest that stratification of patients with heart failure with preserved ejection fraction (HFpEF) according to left ventricular ejection fraction (LVEF) provides a means for dissecting different treatment responses. However, the differential pathophysiologic considerations have rarely been described., Methods: This prospective, single-center study analyzed consecutive symptomatic patients with HFpEF diagnosed according to the 2016 European Society of Cardiology heart failure guidelines. Patients were grouped into LVEF 50% to 60% and LVEF >60% cohorts. All patients underwent cardiac magnetic resonance imaging. Transfemoral cardiac catheterization was performed to derive load-dependent and load-independent left ventricular (LV) properties on pressure-volume loop analyses., Results: Fifty-six patients with HFpEF were enrolled and divided into LVEF 50% to 60% (n=21) and LVEF >60% (n=35) cohorts. On cardiac magnetic resonance imaging, the LVEF >60% cohort showed lower LV end-diastolic volumes ( P =0.019) and end-systolic volumes ( P =0.001) than the LVEF 50% to 60% cohort; stroke volume ( P =0.821) did not differ between the cohorts. Extracellular volume fraction was higher in the LVEF 50% to 60% cohort than in the LVEF >60% cohort (0.332 versus 0.309; P =0.018). Pressure-volume loop analyses demonstrated higher baseline LV contractility (end-systolic elastance, 1.85 vs 1.33 mm Hg/mL; P <0.001) and passive diastolic stiffness (β constant, 0.032 versus 0.018; P =0.004) in the LVEF >60% cohort. Ventriculo-arterial coupling (end-systolic elastance/arterial elastance) at rest was in the range of optimized stroke work in the LVEF >60% cohort but was impaired in the LVEF 50% to 60% cohort (1.01 versus 0.80; P =0.005). During handgrip exercise, patients with LVEF >60% had higher increases in end-systolic elastance (1.85 versus 0.82 mm Hg/mL; P =0.023), attenuated increases in indexed end-systolic volume (-1 versus 7 mL/m²; P <0.004), and more exaggerated increases in LV filling pressures (8 vs 5 mm Hg; P =0.023). LV stroke volume decreased in the LVEF >60% cohort ( P =0.007) under exertion., Conclusions: Patients with HFpEF in whom LVEF ranged from 50% to 60% demonstrated reduced contractility, impaired ventriculo-arterial coupling, and higher extracellular volume fraction. In contrast, patients with HFpEF and a LVEF >60% demonstrated a hypercontractile state with excessive LV afterload and diminished preload reserve. A LVEF-based stratification of patients with HFpEF identified distinct morphologic and pathophysiologic subphenotypes.

Background: Despite recent advances in the treatment of heart failure with preserved ejection fraction (HFpEF), the overall outcome is poor and evidence-based therapeutic options are scarce. So far, the only evidence-based therapy in HFpEF, sodium glucose linked transporter 2 inhibitors, has only insignificant effects in patients with a high EF (EF > 60%, HEF) when compared to a normal EF (EF 50%-60%, NEF). This could be explained by different biomechanical and cellular phenotypes of HFpEF across the range of EFs rather than a uniform pathophysiology. We aimed to investigate the concept of different phenotypes in the HEF and NEF using noninvasive single-beat estimations and to observe alterations in pressure-volume relations in both groups following sympathomodulation using renal denervation (RDN)., Methods: Patients from a previous study on RDN in HFpEF were stratified by having HFpEF with an HEF or NEF. Single-beat estimations were used to derive arterial elastance (Ea), end-systolic elastance (Ees), and diastolic capacitance (VPED 20 )., Results: Overall, 63 patients were classified as having an HEF, and 36 patients were classified as having an NEF. Ea did not differ between the groups and was reduced at follow-up in both groups ( p < 0.01). Ees was higher and VPED 20 was lower in the HEF than those in the NEF. Both were changed significantly at follow-up in the HEF but not in the NEF. Ees/Ea was lower in the NEF (0.95 ± 0.22 vs 1.15 ± 0.27, p < 0.01) and was significantly increased in the NEF (by 0.08 ± 0.20, p < 0.05) but not in the HEF., Conclusions: Beneficial effects of RDN were observed in the NEF and HEF, supporting the further investigation of sympathomodulating treatments for HFpEF in future trials., Competing Interests: P.L. and K.F. received modest institutional fees from ReCor Medical (Palo Alto, CA, USA) and Medtronic (Minneapolis, MN, USA). The remaining authors have nothing to disclosure., (© 2022 The Author(s).)

Background: Transcatheter treatment techniques for tricuspid regurgitation (TR) have evolved in recent years, with leaflet repair being the most commonly used, but thus far evidence on the PASCAL and PASCAL Ace system is based mainly on compassionate use data., Objectives: This is the first report on commercial use in a multicenter study with a large patient cohort investigating the safety and efficacy of the PASCAL and PASCAL Ace system in the treatment of TR., Methods: In a retrospective, multicenter, observational setting, data from all consecutive patients undergoing leaflet repair for TR at 8 centers was collected, including a centralized analysis of echocardiographic data., Results: A total of 235 high-risk patients (mean age 78 ± 8 years, 49% women, mean Society of Thoracic Surgeons Predicted Risk of Mortality score 8.6% ± 6.8%) were included. TR was functional in 87% of patients and graded severe or higher in 91%. TR was successfully reduced to moderate or less in 78% of patients (P < 0.001). Procedural success was 78% (n = 153). At the latest available follow-up (median 173 days), TR reduction was sustained (78% with TR moderate or less; P < 0.001), and echocardiography showed indications of right ventricular remodeling (mean right ventricular end-diastolic diameter 56 ± 9 mm vs 53 ± 9 mm; P < 0.001). Patients' symptoms diminished significantly (63% were in New York Heart Association functional class I or II at follow-up; P < 0.001). In a device-specific analysis, the PASCAL and PASCAL Ace showed no difference in TR reduction (postprocedural TR moderate or less in 77% vs 78%; P = 0.82)., Conclusions: In early clinical experience, the PASCAL (Ace) leaflet repair system has high technical and procedural success rates with efficient TR reduction and significant clinical and echocardiographic improvement at follow-up., Competing Interests: Funding Support and Author Disclosures Dr Praz has received travel expenses from Abbott Vascular, Polares Medical, and Edwards Lifesciences. Dr Higuchi has received lecture fees from Medtronic Japan, Daiichi-Sankyo, and Ono Pharmaceutical Company. Dr Luedike has received speaker fees from Edwards Lifesciences. Dr Rassaf has received speaker fees from AstraZeneca, Daiichi-Sankyo, Bayer, Novartis, and Abiomed outside the submitted work. Dr Braun has received speaker honoraria from Abbott Vascular. Dr Lurz has received grants from Abbott Vascular, Edwards Lifesciences, and ReCor Medical. Dr Hausleiter has received research support and speaker honoraria from Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate changes in quality of life (QoL) after transcatheter tricuspid valve repair (TTVR) for tricuspid regurgitation (TR)., Background: TTVR provides feasible and durable efficacy in reducing TR, but its clinical benefits on QoL still remain unclear., Methods: In 115 subjects undergoing TTVR for severe functional TR, QoL was evaluated using the 36-Item Short Form Health Survey (SF-36) and the Minnesota Living With Heart Failure Questionnaire (MLHFQ). All-cause mortality, heart failure (HF) rehospitalization, and a composite endpoint of all-cause mortality, HF rehospitalization, and repeat TTVR were recorded as clinical events., Results: Successful device implantation was achieved in 110 patients (96%). Moderate or less TR at discharge was achieved in 95 patients (83%). Mean SF-36 physical component summary (PCS) score improved from 34 ± 9 to 37 ± 9 points (+3 points; 95% CI: 1-5 points; P = 0.001), mean SF-36 mental component summary score improved from 49 ± 9 to 51 ± 10 points (+2 points; 95% CI: 0-4 points; P = 0.017), and mean MLHFQ score decreased from 29 ± 14 to 20 ± 15 points (-8 points; 95% CI: -11 to -5 points; P < 0.001). Baseline PCS, moderate or less TR at discharge, and baseline massive or torrential TR were associated with 1-month change in PCS score (P < 0.05). Change in PCS score after 1 month predicted HF rehospitalization after TTVR (adjusted HR: 0.74 [95% CI: 0.60-0.92] per 5-point increase in PCS score; P = 0.008)., Conclusions: This study demonstrates that TTVR provides improvement in QoL in patients with relevant TR. TR reduction to a moderate or less grade was associated with improvement of SF-36 and MLHFQ scores. Further, global QoL was associated with clinical outcomes and might serve as a future outcome surrogate following TTVR., Competing Interests: Funding Support and Author Disclosures Dr Lurz has been a consultant to Abbott Structural Heart, Edwards Lifesciences, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

For a long time, severe tricuspid valve regurgitation (TR) was an underestimated disease, especially in the older population and was associated with high morbidity and mortality. Due to the high perioperative mortality of tricuspid valve surgery, historically only pharmaceutical treatment was a practical treatment option. In the first studies interventional approaches could achieve promising results with an effective reduction of TR with simultaneous proof of a convincing safety profile. Conceptually, the currently available interventional treatment options can be divided into three concepts: coaptation systems (edge-to-edge repair), annuloplasty and interventional valve replacement. The largest clinical experience and best scientific body of evidence could so far be generated in the field of coaptation systems. Very promising preliminary results with effective reduction of TR and improvement of the clinical symptoms are, however, also available for interventional valve replacement. Meticulous preprocedural diagnostics with selection of the most suitable treatment option for each individual patient is paramount for successful treatment in this critically ill patient cohort. Future prospective randomized studies will investigate the net benefit of an interventional treatment of TR in comparison to a purely conservative treatment concept., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Osteoporosis is a common metabolic disorder diagnosed by lower bone density and higher risk of fracture. Fragility fractures because of osteoporosis are associated with high mortality rate. Deep understanding of fracture healing in osteoporosis is important for successful treatment. Therefore, the FDA approved the use of small and large animal models for preclinical testing. This study investigated the clinical relevance of a fracture defect model in the iliac crest of the osteoporotic sheep model and its several advantages over other models. The osteoporosis was achieved using ovariectomy (OVX) in combination with diet deficiency (OVXD) and steroid administration (OVXDS). Fluorochrome was injected to examine the rate of bone remodelling and bone mineralization. The defect areas were collected and embedded in paraffin and polymethyl metha acrylate (PMMA) for histological staining. OVXDS showed significantly lower bone mineral density (BMD) and bone mineral content (BMC) at all time points. Furthermore, variations in healing patterns were noticed, while the control, OVX and OVXD showed complete healing after 8 months. Bone quality was affected mostly in the OVXDS group showing irregular trabecular network, lower cortical bone thickness and higher cartilaginous tissue at 8 months. The mineral deposition rate showed a declining pattern in the control, OVX, and OVXD from 5 months to 8 months. One the contrary, the OVXDS group showed an incremental pattern from 5 months to 8 months. The defect zone in osteoporotic animals showed impaired healing and the control showed complete healing after 8 months. This unique established model serves as a dual-purpose model and has several advantages: no intraoperative and postoperative complications, no need for fixation methods for biomaterial testing, and reduction in animal numbers, which comply with 3R principles by using the same animal at two different time points.

Heart failure with preserved ejection fraction (HFpEF) is increasing in incidence and has a higher prevalence compared with heart failure with reduced ejection fraction. So far, no effective treatment of HFpEF is available, due to its complex underlying pathophysiology and clinical heterogeneity. This article aims to provide an overview and a future perspective of transcriptomic biomarker research in HFpEF. Detailed characterisation of the HFpEF phenotype and its underlying molecular pathomechanisms may open new perspectives regarding early diagnosis, improved prognostication, new therapeutic targets and tailored therapies accounting for patient heterogeneity, which may improve quality of life. A combination of cross-sectional and longitudinal study designs with sufficiently large sample sizes are required to support this concept., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © 2020, Radcliffe Cardiology.)

Bone histomorphometry allows quantitative evaluation of bone micro-architecture, bone formation, and bone remodeling by providing an insight to cellular changes. Histomorphometry plays an important role in monitoring changes in bone properties because of systemic skeletal diseases like osteoporosis and osteomalacia. Besides, quantitative evaluation plays an important role in fracture healing studies to explore the effect of biomaterial or drug treatment. However, until today, to our knowledge, bone histomorphometry remain time-consuming and expensive. This incited us to set up an open-source freely available semi-automated solution to measure parameters like trabecular area, osteoid area, trabecular thickness, and osteoclast activity. Here in this study, the authors present the adaptation of Trainable Weka Segmentation plugin of ImageJ to allow fast evaluation of bone parameters (trabecular area, osteoid area) to diagnose bone related diseases. Also, ImageJ toolbox and plugins (BoneJ) were adapted to measure osteoclast activity, trabecular thickness, and trabecular separation. The optimized two different scripts are based on ImageJ, by providing simple user-interface and easy accessibility for biologists and clinicians. The scripts developed for bone histomorphometry can be optimized globally for other histological samples. The showed scripts will benefit the scientific community in histological evaluation.

Statement of Problem: The passive fit of superstructures for implant-supported restorations is affected by each step of the fabrication process. In this context the question arises whether ceramic veneering would increase static implant loading., Purpose: The purpose of this study was to quantify the strain development of various fixed partial dentures (FPDs) both in the as-cast condition and after ceramic veneering., Material and Methods: Four different types (n = 10) of 5-unit FPDs (cementable, screw retained/plastic cylinder, screw retained/gold cylinder, screw retained/cemented) representing commonly used types of FPDs were investigated before and after ceramic veneering. Three implants were placed in a model simulating a patient situation, and strain gauges were mounted mesially and distally adjacent to the implants. The strain development was recorded during cement setting (provisional cement) and screw fixation. The data were analyzed statistically using multivariate 2-sample tests (alpha=.1)., Results: All FPDs revealed measurable amounts of strain. Neither the type of retention nor the mode of fabrication for conventional screw-retained FPDs had a significant influence on strain development. Ceramic veneering caused an increase in strain development for the conventional fixed partial dentures tested. The lowest strains were found in FPDs cemented to gold cylinders on the model for the metal frames and the ceramic-veneered FPDs., Conclusion: Conventional procedures were unable to produce superstructures with absolute passive fit. Ceramic veneering appeared to increase strain development and, thus, inaccuracy of the fit. The technique of cementing superstructures to prefabricated components directly on the implants may compensate for dimensional errors caused by impression making and superstructure fabrication.