Novel Long Noncoding RNA HEAT4 Affects Monocyte Subtypes, Reducing Inflammation and Promoting Vascular Healing.

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.

2-Year Outcomes of an Atrial Shunt Device in HFpEF/HFmrEF: Results From REDUCE LAP-HF II.

BACKGROUND: The REDUCE LAP-HF II (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II) trial found that, compared with a sham procedure, the Corvia Atrial Shunt did not improve outcomes in heart failure with preserved or mildly reduced ejection fraction. However, after 12-month follow-up, "responders" (peak-exercise pulmonary vascular resistance <1.74 WU and absence of a cardiac rhythm management device) were identified. OBJECTIVES: This study sought to determine: 1) the overall efficacy and safety of the atrial shunt vs sham control after 2 years of follow-up; and 2) whether the benefits of atrial shunting are sustained in responders during longer-term follow-up or are offset by adverse effects of the shunt. METHODS: The study analyzed 2-year outcomes in the overall REDUCE LAP-HF II trial, as well as in responder and nonresponder subgroups. The primary endpoint was a hierarchical composite of cardiovascular death or nonfatal ischemic/embolic stroke, total heart failure events, and change in health status. RESULTS: In 621 randomized patients, there was no difference between the shunt (n = 309) and sham (n = 312) groups in the primary endpoint (win ratio: 1.01 [95% CI: 0.82-1.24]) or its individual components at 2 years. Shunt patency at 24 months was 98% in shunt-treated patients. Cardiovascular mortality and nonfatal ischemic stroke were not different between the groups; however, major adverse cardiac events were more common in those patients assigned to the shunt compared with sham (6.9% vs 2.7%; P = 0.018). More patients randomized to the shunt had an increase in right ventricular volume of ≥30% compared with the sham control (39% vs 28%, respectively; P < 0.001), but right ventricular dysfunction was uncommon and not different between the treatment groups. In responders (n = 313), the shunt was superior to sham (win ratio: 1.36 [95% CI: 1.02-1.83]; P = 0.037, with 51% fewer HF events [incidence rate ratio: 0.49 [95% CI: 0.25-0.95]; P = 0.034]). In nonresponders (n = 265), atrial shunting was inferior to sham (win ratio: 0.73 [95% CI: 0.54-0.98]). CONCLUSIONS: At 2 years of follow-up in REDUCE LAP-HF II, there was no difference in efficacy between the atrial shunt and sham groups in the overall trial group. The potential clinical benefit identified in the responder group after 1 and 2 years of follow-up is currently being evaluated in the RESPONDER-HF (Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction Heart Failure) trial. (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II [REDUCE LAP-HF II]; NCT03088033).

TRISCEND II: Novel Randomized Trial Design for Transcatheter Tricuspid Valve Replacement.

Severe tricuspid regurgitation remains largely undertreated given limited treatment options. Transcatheter tricuspid valve interventions have emerged as a promising therapy for these patients, and the TRISCEND II pivotal trial is the first randomized controlled trial to evaluate transcatheter tricuspid valve replacement (TTVR). The TRISCEND II pivotal trial studies the transcatheter EVOQUE (Edwards Lifesciences, Irvine, California) tricuspid valve replacement system using a United States Food and Drug Administration Breakthrough Device Designation-a program intended to provide timely access to medical devices by speeding up development, assessment, and review. The TRISCEND II trial is a prospective, multicenter trial that randomizes patients with symptomatic severe tricuspid regurgitation to treatment with either TTVR in conjunction with optimal medical therapy or optimal medical therapy alone. The trial's novel 2-phase design evaluates 30-day safety and 6-month effectiveness end points for the first 150 patients in the initial phase and a 1-year safety and effectiveness end point for the full cohort of 400 patients in the second phase. The TRISCEND II trial's 2-phase trial design provided an opportunity for early review and led to the first commercial approval of a TTVR system. In conclusion, the design of the TRISCEND II trial will likely inform future transcatheter tricuspid device trials.

Association between socioeconomic and psychosocial factors with use of interventional and surgical treatments and outcomes in patients with myocardial infarction - Inpatient data of the largest European health care system.

BACKGROUND: Myocardial infarction (MI) is an important driver of both morbidity and mortality on a global scale. Elucidating social inequalities may help to identify vulnerable groups as well as treatment imbalances and guide efforts to improve care for MI. METHODS: All hospitalized patient-cases with confirmed MI 2005-2020 in Germany were included in the study and stratified for socioeconomic or psychosocial factors (SPF) and the impact of SPF on treatment usage and adverse in-hospital events was analyzed. RESULTS: Overall, 4,409,597 hospitalizations of MI patients were included; of these, 17,297 (0.4 %) were coded with SPF. These patients were more often of female sex (49.4 % vs. 36.9 %, P<0.001), older (median 77.0 [IQR: 65.0-84.0] vs. 73.0 [62.0-81.0] years, P<0.001) and revealed an aggravated cardiovascular profile. Although SPF were independently associated with increased usage of cardiac catheterization (OR 1.174 [95 %CI 1.136-1.212]) and percutaneous coronary intervention (OR 1.167 [95 %CI 1.130-1.205]), they were accompanied by higher risk for a prolonged length of in-hospital stay >7 days (OR 1.236 [95 %CI 1.198-1.276]) and >10 days (OR 1.296 [95 %CI 1.254-1.339]). While SPF were associated with increased risk for deep venous thrombosis and/or thrombophlebitis (OR 1.634 [95 %CI 1.427-1.870]), pulmonary embolism (OR 1.337 [95 %CI 1.149-1.555]), and acute renal failure (OR 1.170 [95 %CI 1.105-1.240), these SPF were inversely associated with in-hospital case-fatality (OR 0.461 [95 %CI 0.433-0.490]). CONCLUSIONS: This study demonstrates that SPF in hospitalized MI patients have significant impacts on treatments and outcomes. Fortunately, our data did not revealed an underuse of interventional treatments in MI patients with SPF.

Guideline-Directed Medical Therapy and Survival After TEER for Secondary Mitral Regurgitation With Right Ventricular Impairment.

BACKGROUND: Right ventricular impairment is common among patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation (SMR). Adherence to guideline-directed medical therapy (GDMT) for heart failure is poor in these patients. OBJECTIVES: The aim of this study was to evaluate the impact of GDMT on long-term survival in this patient cohort. METHODS: Within the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) international registry, we selected patients with SMR and right ventricular impairment (tricuspid annular plane systolic excursion ≤17 mm and/or echocardiographic right ventricular-to-pulmonary artery coupling <0.40 mm/mm Hg). Titrated guideline-directed medical therapy (GDMTtit) was defined as a coprescription of 3 drug classes with at least one-half of the target dose at the latest follow-up. The primary outcome was all-cause mortality at 6 years. RESULTS: Among 1,213 patients with SMR and right ventricular impairment, 852 had complete data on medical therapy. The 123 patients who were on GDMTtit showed a significantly higher long-term survival vs the 729 patients not on GDMTtit (61.8% vs 36.0%; P < 0.00001). Propensity score-matched analysis confirmed a significant association between GDMTtit and higher survival (61.0% vs 43.1%; P = 0.018). GDMTtit was an independent predictor of all-cause mortality (HR: 0.61; 95% CI: 0.39-0.93; P = 0.02 for patients on GDMTtit vs those not on GDMTtit). Its association with better outcomes was confirmed among all subgroups analyzed. CONCLUSIONS: In patients with right ventricular impairment undergoing transcatheter edge-to-edge repair for SMR, titration of GDMT to at least one-half of the target dose is associated with a 40% lower risk of all-cause death up to 6 years and should be pursued independent of comorbidities.

Prognostic Implications of Residual Tricuspid Regurgitation Grading After Transcatheter Tricuspid Valve Repair.

BACKGROUND: The safety profile of transcatheter tricuspid valve (TTV) repair techniques is well established, but residual tricuspid regurgitation (TR) remains a concern. OBJECTIVES: The authors sought to assess the impact of residual TR severity post-TTV repair on survival. METHODS: We evaluated the survival rate at 2 years of 613 patients with severe isolated functional TR who underwent TTV repair in TRIGISTRY according to the severity of residual TR at discharge using a 3-grade (mild, moderate, and severe) or 4-grade scheme (mild, mild to moderate, moderate to severe, and severe). RESULTS: Residual TR was none/mild in 33%, moderate in 52%, and severe in 15%. The 2-year adjusted survival rates significantly differed between the 3 groups (85%, 70%, and 44%, respectively; restricted mean survival time [RMST]: P = 0.0001). When the 319 patients with moderate residual TR were subdivided into mild to moderate (n = 201, 33%) and moderate to severe (n = 118, 19%), the adjusted survival rate was also significantly different between groups (85%, 80%, 55%, and 44%, respectively; RMST: P = 0.001). Survival was significantly lower in patients with moderate to severe residual TR compared to patients with mild to moderate residual TR (P = 0.006). No difference in survival rates was observed between patients with no/mild and mild to moderate residual TR (P = 0.67) or between patients with moderate to severe and severe residual TR (P = 0.96). CONCLUSIONS: The moderate residual TR group was heterogeneous and encompassed patients with markedly different clinical outcomes. Refining TR grade classification with a more granular 4-grade scheme improved outcome prediction. Our results highlight the importance of achieving a mild to moderate or lower residual TR grade during TTV repair, which could define a successful intervention.

Real-World 1-Year Results of Tricuspid Edge-to-Edge Repair From the bRIGHT Study.

BACKGROUND: Severe tricuspid regurgitation (TR) is known to be associated with poor quality of life and increased risk of death when left untreated. OBJECTIVES: We sought to report the 1-year clinical outcomes of subjects treated by tricuspid transcatheter edge-to-edge repair (TEER) with the TriClip system (Abbott Cardiovascular) in a contemporary real-world setting. METHODS: The bRIGHT (An Observational Real-World Study Evaluating Severe Tricuspid Regurgitation Patients Treated With the Abbott TriClip Device) postapproval study is a prospective, single-arm, open-label, multicenter postmarket registry conducted at 26 sites in Europe, with central event adjudication and echocardiographic core-laboratory assessment. RESULTS: Enrolled subjects (n = 511) were elderly (79 ± 7 years) with significant comorbidities. A total of 88% had baseline massive or torrential TR, and 80% of subjects were in NYHA functional class III/IV. TR was reduced to moderate or less in 81% at 1 year. Significant improvements in NYHA functional class (21% to 75% I/II, P < 0.0001) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score (19 ± 26-point improvement, P <0.0001) were observed at 1 year. One-year mortality was significantly lower in subjects who achieved moderate or lower TR at 30 days; however, there was no difference in mortality among subjects who achieved moderate, mild, or trace TR at 30 days. In addition to TR reduction at 30 days, baseline serum creatinine and baseline right ventricular tricuspid annular plane systolic excursion (RV TAPSE) were independently associated with mortality at 1 year (OR: 2.169; 95% CI: 1.494-3.147; P < 0.0001; OR: 0.636; 95% CI: 0.415-0.974; P = 0.0375). Mortality was not associated with baseline TR grade or with center volume. CONCLUSIONS: Tricuspid TEER using the TriClip system was safe and effective through 1 year for subjects with significant TR and advanced disease in a diverse real-world population. (An Observational Real-world Study Evaluating Severe Tricuspid Regurgitation Patients Treated With the Abbott TriClip Device [bRIGHT]; NCT04483089).

App-Based Mental Training to Reduce Atrial Fibrillation-Related Symptoms After Pulmonary Vein Isolation: MENTAL AF Trial.

BACKGROUND: Even after atrial fibrillation (AF) catheter ablation, many patients still experience relevant symptom burden. The objective of the MENTAL AF trial was to determine whether app-based mental training (MT) during the 3 months following pulmonary vein isolation reduces AF-related symptoms. METHODS AND RESULTS: Patients scheduled for pulmonary vein isolation were enrolled and randomized 1:1 to either app-based MT or usual care. Of 174 patients, 76 in the MT and 75 in the usual care group were included in the final analysis. The intervention was delivered by a daily 10-minute app-based MT. The primary outcome was the intergroup difference of the mean AF6 sum score, an AF-specific questionnaire, during the 3-month study period. Secondary outcomes included quality-of-life measures such as the AFEQT (Atrial Fibrillation Effect on Quality of Life). Mean age (SD) was 61 (8.7) years and 61 (41%) were women. The mean AF6 sum score over the study period was 8.9 (6.9) points in the MT group and 12.5 (10.1) in the usual care group (P=0.011). This referred to a reduction in the AF6 sum score compared with baseline of 75% in MT and 52% for usual care (P<0.001). The change in the AFEQT Global Score was 22.6 (16.3) and 15.7 (22.1), respectively; P=0.026. CONCLUSIONS: MENTAL AF showed that app-based MT as an adjunctive treatment tool following pulmonary vein isolation was feasible. App-based MT was found to be superior to standard care in reducing AF-related symptom burden and improving health-related quality of life. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04067427.

Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry.

AIMS: Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. METHODS AND RESULTS: Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm2). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012). CONCLUSIONS: T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction.

Impact of heart failure hospitalizations on clinical outcomes after mitral transcatheter edge-to-edge repair: Results from the EXPAND study.

AIM: This analysis aimed to compare the clinical outcomes associated with heart failure (HF) readmissions and to identify associations with HF hospitalizations (HFH) in patients treated with the MitraClip™ NTR/XTR System in the EXPAND study. METHODS AND RESULTS: The global, real-world EXPAND study enrolled 1041 patients with primary or secondary mitral regurgitation (MR) treated with the MitraClip NTR/XTR System. Echocardiograms were analysed by an independent echocardiographic core laboratory. The study population was stratified into HFH and No-HFH groups based on the occurrence of HFH 1 year post-index procedure. Clinical outcomes including MR severity, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and all-cause mortality were compared (HFH: n = 181; No-HFH: n = 860). Both groups achieved consistent 1-year MR reduction to ≤1+ (HFH vs. No-HFH: 87.3% vs. 89.5%, p = 0.6) and significant 1-year improvement in KCCQ scores (+16.5 vs. +22.3, p = 0.09) and NYHA functional class. However, more patients in the No-HFH group had 1-year NYHA class ≤II (HFH vs. No-HFH: 67.9% vs. 81.9%, p < 0.01). All-cause mortality at 1 year was 36.8% in the HFH group versus 10.4% in the No-HFH group (p < 0.001). The HFH rate decreased by 63% at 1 year post-M-TEER versus 1 year pre-treatment (relative risk 0.4, p < 0.001). Independent HFH associations were MR ≥2+ at discharge, HFH 1 year prior to treatment, baseline NYHA class ≥III, baseline tricuspid regurgitation ≥2+, and baseline left ventricular ejection fraction ≤40%. CONCLUSIONS: This study reports the impact of HFH on clinical outcomes post-treatment in the EXPAND study. Results demonstrate that the occurrence of HFH was associated with worse 1-year survival, and treatment with the MitraClip system substantially reduced HFH and improved patient symptoms and quality of life.

New Approaches to Assessment and Management of Tricuspid Regurgitation Before Intervention.

Severe tricuspid regurgitation (TR) is a progressive condition associated with substantial morbidity, poor quality of life, and increased mortality. Patients with TR commonly have coexisting conditions including congestive heart failure, pulmonary hypertension, chronic lung disease, atrial fibrillation, and cardiovascular implantable electronic devices, which can increase the complexity of medical and surgical TR management. As such, the optimal timing of referral for isolated tricuspid valve (TV) intervention is undefined, and TV surgery has been associated with elevated risk of morbidity and mortality. More recently, an unprecedented growth in TR treatment options, namely the development of a wide range of transcatheter TV interventions (TTVI) is stimulating increased interest and referral for TV intervention across the entire medical community. However, there are no stepwise algorithms for the optimal management of symptomatic severe TR before TTVI. This article reviews the contemporary assessment and management of TR with addition of a medical framework to optimize TR before referral for TTVI.

Mitral Valve Transcatheter Edge-to-Edge Repair: 1-Year Outcomes From the MiCLASP Study.

BACKGROUND: Mitral transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with severe symptomatic mitral regurgitation (MR). Outcomes with the PASCAL system in a post-market setting have not been established. OBJECTIVES: The authors report 30-day and 1-year outcomes from the MiCLASP (Transcatheter Repair of Mitral Regurgitation with Edwards PASCAL Transcatheter Valve Repair System) European post-market clinical follow-up study. METHODS: Patients with symptomatic, clinically significant MR were prospectively enrolled. The primary safety endpoint was clinical events committee-adjudicated 30-day composite major adverse event rate and the primary effectiveness endpoint was echocardiographic core laboratory-assessed MR severity at discharge compared with baseline. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year. RESULTS: A total of 544 patients were enrolled (59% functional MR, 30% degenerative MR). The 30-day composite major adverse event rate was 6.8%. MR reduction was significant from baseline to discharge and sustained at 1 year with 98% of patients achieving MR ≤2+ and 82.6% MR ≤1+ (all P < 0.001 vs baseline). One-year Kaplan-Meier estimate for survival was 87.3%, and freedom from heart failure hospitalization was 84.3%. Significant functional and quality-of-life improvements were observed at 1 year, including 71.6% in NYHA functional class I/II, 14.4-point increase in Kansas City Cardiomyopathy Questionnaire score, and 24.2-m improvement in 6-minute walk distance (all P < 0.001 vs baseline). CONCLUSIONS: One-year outcomes of this large cohort from the MiCLASP study demonstrate continued safety and effectiveness of M-TEER with the PASCAL system in a post-market setting. Results demonstrate high survival and freedom from heart failure hospitalization, significant and sustained MR reduction, and improvements in symptoms, functional capacity, and quality of life.

Clinical Trajectory and Risk Stratification for Heart Failure with Preserved Ejection Fraction in a Real-World Cohort of Patients with Suspected Coronary Artery Disease.

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 H2FPEF 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 H2FPEF 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 H2FPEF 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 H2FPEF 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 H2FPEF score helps in risk-stratifying patients for HF hospitalization and mortality.

Congestion patterns in severe tricuspid regurgitation and transcatheter treatment: Insights from a multicentre registry.

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.

Injection Site Matters: A Comparative Analysis of Transpulmonary Thermodilution via Simultaneous Femoral and Jugular Indicator Injections under Veno-Venous Extracorporeal Membrane Oxygenation Therapy.

Background: The use of veno-venous extracorporeal membrane oxygenation (vv-ECMO) in acute lung failure has witnessed a notable increase. The PiCCO system is frequently used for advanced hemodynamic monitoring in this cohort. Our study aimed to investigate whether the choice of indicator injection site (jugular vs. femoral) in patients undergoing vv-ECMO therapy affects transpulmonary thermodilution (TPTD) measurements using the PiCCO® device (Pulsion Medical Systems SE, Munich, Germany). Methods: In a retrospective single-center analysis, we compared thermodilution-derived hemodynamic parameters after simultaneous jugular and femoral injections in 28 measurements obtained in two patients with respiratory failure who were undergoing vv-ECMO therapy. Results: Elevated values of the extravascular lung water index (EVLWI), intrathoracic blood volume index (ITBVI) and global end-diastolic volume index (GEDVI) were observed following femoral indicator injection compared to jugular indicator injection (EVLWI: 29.3 ± 10.9 mL/kg vs. 18.3 ± 6.71 mL/kg, p = 0.0003; ITBVI: 2163 ± 631 mL/m2 vs. 806 ± 125 mL/m2, p < 0.0001; GEDVI: 1731 ± 505 mL/m2 vs. 687 ± 141 mL/m2, p < 0.0001). The discrepancy between femoral and jugular measurements exhibited a linear correlation with extracorporeal blood flow (ECBF). Conclusions: In a PiCCO®-derived hemodynamic assessment of patients on vv-ECMO, the femoral indicator injection, as opposed to the jugular injection, resulted in an overestimation of all index parameters. This discrepancy can be attributed to mean transit time (MTt) and downslope time-dependent (DSt) variations in GEDVI and cardiac function index and is correlated with ECBF.

Prediction of Mortality and Heart Failure Hospitalization After Transcatheter Tricuspid Valve Interventions: Validation of TRISCORE.

BACKGROUND: Data on the prognostic role of the TRI-SCORE in patients undergoing transcatheter tricuspid valve intervention (TTVI) are limited. OBJECTIVES: The aim of this study was to evaluate the performance of the TRI-SCORE in predicting outcomes of patients undergoing TTVI. METHODS: TriValve (Transcatheter Tricuspid Valve Therapies) is a large multicenter multinational registry including patients undergoing TTVI. The TRI-SCORE is a risk model recently proposed to predict in-hospital mortality after tricuspid valve surgery. The TriValve population was stratified based on the TRI-SCORE tertiles. The outcomes of interest were all-cause death and all-cause death or heart failure hospitalization. Procedural complications and changes in NYHA functional class were also reported. RESULTS: Among the 634 patients included, 223 patients (35.2%) had a TRI-SCORE between 0 and 5, 221 (34.8%) had 6 or 7, and 190 (30%) had ≥8 points. Postprocedural blood transfusion, acute kidney injury, new atrial fibrillation, and in-hospital mortality were more frequent in the highest TRI-SCORE tertile. Postprocedure length of stay increased with a TRI-SCORE increase. A TRI-SCORE ≥8 was associated with an increased risk of 30-day all-cause mortality and all-cause mortality and the composite endpoint assessed at a median follow-up of 186 days (OR: 3.00; 95% CI: 1.38-6.55; HR: 2.17; 95% CI: 1.78-4.13; HR: 2.08, 95% CI: 1.57-2.74, respectively) even after adjustment for procedural success and EuroSCORE II or Society of Thoracic Surgeons Predicted Risk of Mortality. The NYHA functional class improved across all TRI-SCORE values. CONCLUSIONS: In the TriValve registry, the TRI-SCORE has a suboptimal performance in predicting clinical outcomes. However, a TRISCORE ≥8 is associated with an increased risk of clinical events and a lack of prognostic benefit after successful TTVI.

Categorization of Patients with Pulmonary Embolism by Charlson Comorbidity Index.

BACKGROUND: Short-term outcomes of pulmonary embolism are closely related to right ventricular dysfunction and patient's hemodynamic status, but also to individual comorbidity profile. However, the impact of patients' comorbidities on survival during pulmonary embolism might be underrated. Although the Charlson Comorbidity Index (CCI) is the most extensively studied comorbidity index for detecting comorbidity burden, studies analyzing the impact of CCI on pulmonary embolism patients' survival are limited. METHODS: We used the German nationwide inpatient sample to analyze all hospitalized patients with pulmonary embolism in Germany 2005-2020 and calculated CCI for each patient, compared the CCI classes (very low: CCI = 0 points, mild: CCI = 1-2 points, moderate: CCI = 3-4, high severity: CCI >4 points) and impact of CCI class on outcomes. RESULTS: Overall, 1,373,145 hospitalizations of patients with acute pulmonary embolism (53.0% females, 55.9% aged ≥70 years) were recorded in Germany between 2005 and 2020; the CCI class stratified them. Among these, 100,156 (7.3%) were categorized as very low; 221,545 (16.1%) as mild; 394,965 (28.8%) as moderate; and 656,479 (47.8%) as patients with a high comorbidity burden according to CCI class. In-hospital case fatality increased depending on the CCI class: 3.6% in very low, 6.5% in mild, 12.1% in moderate, and 22.1% in high CCI class (P < .001). CCI class was associated with increased in-hospital case fatality (odds ratio 2.014; 95% confidence interval, 2.000-2.027; P < .001). CONCLUSION: Our study results may help practitioners to better understand and measure the association between an aggravated comorbidity profile and increased in-hospital case fatality in patients with pulmonary embolism.

Transthyretin amyloid cardiomyopathy among patients with heart failure and preserved ejection fraction: the AMY score.

AIMS: Transthyretin 'wild-type' amyloid cardiomyopathy (ATTRwt-CM) is a differential diagnosis of heart failure with preserved ejection fraction (HFpEF). The clinical work-up for ATTRwt-CM is challenging. Considering a combination of clinical variables specific for ATTRwt-CM might aid in identifying patients at risk. METHODS AND RESULTS: Sixty patients (78 ± 6 years, 8% female) were diagnosed with ATTRwt-CM by endomyocardial biopsy. Preserved ejection fraction (LVEF >45%) was present in 41 of the patients. Those were 1:1 propensity score age- and sex-matched to a cohort of patients with HFpEF. ATTRwt-CM patients had less obesity (P = 0.01) and higher septal thickness (IVSd, P < 0.01) as well as more diastolic dysfunction (E/e', P < 0.01). On multivariable regression IVSd > 14 mm, E/e' > 14 and absence of obesity (P > 0.01 for all) were identified as predictors for ATTRwt-CM. A weighted point-based score was derived with IVSd > 14 mm = 1 point; absence of obesity = 2 points; and E/e' > 14 = 3 points. Area under the curve (AUC) for the summation score was 0.91 (0.84-0.97, P < 0.01) and a score of more than 3 points predicted ATTRwt-CM with good sensitivity (78%) and specificity (90%). The score was validated in an external cohort of 142 patients with ATTRwt-CM and 419 HFpEF patients showing sufficient accuracy (AUC 0.91, 0.88-0.94, P < 0.01). A value greater than 3 points demonstrated a high sensitivity (93%) and a negative predictive value of 97%. CONCLUSIONS: A score based on basic clinical and echocardiographic features helps to distinguish ATTRwt-CM from typical HFpEF. This could facilitate the diagnostic work-up for these patients and enable earlier disease screening on a large scale.

Implications of tricuspid regurgitation and right ventricular volume overload in patients with heart failure with preserved ejection fraction.

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.