Twenty‐Four‐Month Blood Pressure Results After Renal Denervation Using Endovascular Ultrasound

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

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

Sex-Related Differences in Clinical Characteristics and Outcome Prediction Among Patients Undergoing Transcatheter Tricuspid Valve Intervention.

BACKGROUND Men and women differ regarding comorbidities, pathophysiology, and the progression of valvular heart diseases. OBJECTIVES This study sought to assess sex-related differences regarding clinical characteristics and the outcome of patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI). METHODS All 702 patients in this multicenter study underwent TTVI for severe TR. The primary outcome was 2-year all-cause mortality. RESULTS Among 386 women and 316 men in this study, men were more often diagnosed with coronary artery disease (52.9% in men vs 35.5% in women; P = 5.6 × 10-6). Subsequently, the underlying etiology for TR in men was predominantly secondary ventricular (64.6% in men vs 50.0% in women; P = 1.4 × 10-4), whereas women more often presented with secondary atrial etiology (41.7% in women vs 24.4% in men, P = 2.0 × 10-6). Notably, 2-year survival after TTVI was similar in women and men (69.9% in women vs 63.7% in men; P = 0.144). Multivariate regression analysis identified dyspnea expressed as New York Heart Association functional class, tricuspid annulus plane systolic excursion (TAPSE), and mean pulmonary artery pressure (mPAP) as independent predictors for 2-year mortality. The prognostic significance of TAPSE and mPAP differed between sexes. Consequently, we looked at right ventricular-pulmonary arterial coupling expressed as TAPSE/mPAP and identified sex-specific thresholds to best predict survival; women with a TAPSE/mPAP ratio <0.612 mm/mm Hg displayed a 3.43-fold increased HR for 2-year mortality (P < 0.001), whereas men with a TAPSE/mPAP ratio <0.434 mm/mm Hg displayed a 2.05-fold increased HR for 2-year mortality (P = 0.001). CONCLUSIONS Even though men and women differ in the etiology of TR, both sexes show similar survival rates after TTVI. The TAPSE/mPAP ratio can improve prognostication after TTVI, and sex-specific thresholds should be applied to guide future patient selection

Applying the TRILUMINATE Eligibility Criteria to Real-World Patients Receiving Tricuspid Valve Transcatheter Edge-to-Edge Repair.

BACKGROUND According to the Clinical TRIal to EvaLUate Cardiovascular OutcoMes IN PAtients Treated with the Tricuspid ValvE Repair System (TRILUMINATE) trial, transcatheter tricuspid edge-to-edge repair (T-TEER) improves quality of life beyond medical treatment, while no effects on heart failure hospitalizations (HFH) and survival were observed at 1 year. However, the generalizability of the TRILUMINATE trial to real-world conditions remains subject of discussion. OBJECTIVES To apply the clinical TRILUMINATE in- and exclusion criteria to a real-world T-TEER patient group and evaluate symptomatic and survival outcome in TRILUMINATE eligible and ineligible patients. METHODS Clinical TRILUMINATE in- and exclusion criteria were applied to a cohort of patients who underwent T-TEER at five European centers from 2016 until 2022. Study patients were compared regarding baseline characteristics, survival, HFH, and symptomatic outcomes as measured by New York Heart Association (NYHA) functional class, quality of life questionnaire and six-minute walk test distance (6MWD). RESULTS Out of 962 patients, 54.8% were classified as TRILUMINATE eligible, presenting with superior left ventricular function and fewer comorbidities compared to the ineligible population. TR reduction, improvement in NYHA class, quality of live and exercise capacity were comparable in both groups. However, the 1-year survival and HFH rates significantly differed (TR≤2+ at discharge: 82% vs. 85%; survival: 85% vs. 75%; HFH: 14% vs. 22% for eligible vs. ineligible patients). CONCLUSIONS The observed differences in survival and HFH outcomes suggest a limited generalizability of TRILUMINATE to real-world conditions and they indicate the need for additional studies evaluating the outcomes after T-TEER in less selected patient populations

Epiphenomenon or Prognostically Relevant Interventional Target? A Novel Proportionality Framework for Severe Tricuspid Regurgitation

Background Tricuspid regurgitation (TR) frequently develops in patients with long‐standing pulmonary hypertension, and both pathologies are associated with increased morbidity and mortality. This study aimed to improve prognostic assessment in patients with severe TR undergoing transcatheter tricuspid valve intervention (TTVI) by relating the extent of TR to pulmonary artery pressures. Methods and Results In this multicenter study, we included 533 patients undergoing TTVI for moderate‐to‐severe or severe TR. The proportionality framework was based on the ratio of tricuspid valve effective regurgitant orifice area to mean pulmonary artery pressure. An optimal threshold for tricuspid valve effective regurgitant orifice area/mean pulmonary artery pressure ratio was derived on 353 patients with regard to 2‐year all‐cause mortality and externally validated on 180 patients. Patients with a tricuspid valve effective regurgitant orifice area/mean pulmonary artery pressure ratio ≤1.25 mm2/mm Hg (defining proportionate TR) featured significantly lower 2‐year survival rates after TTVI than patients with disproportionate TR (56.6% versus 69.6%; P=0.005). In contrast with patients with disproportionate TR (n=398), patients with proportionate TR (n=135) showed more pronounced mPAP levels (37.9±9.06 mm Hg versus 27.9±8.17 mm Hg; P<2.2×10−16) and more severely impaired right ventricular function (tricuspid annular plane systolic excursion: 16.0±4.11 versus 17.0±4.64 mm; P=0.012). Moreover, tricuspid valve effective regurgitant orifice area was smaller in patients with proportionate TR when compared with disproportionate TR (0.350±0.105 cm2 versus 0.770±0.432 cm2; P<2.2×10−16). Importantly, proportionate TR remained a significant predictor for 2‐year mortality after adjusting for demographic and clinical variables (hazard ratio, 1.7; P=0.006). Conclusions The proposed proportionality framework promises to improve future risk stratification and clinical decision‐making by identifying patients who benefit the most from TTVI (disproportionate TR). As a next step, randomized controlled studies with a conservative treatment arm are needed to quantify the net benefit of TTVI in patients with proportionate TR

"Artificial Intelligence-Enabled Assessment of Right Ventricular to Pulmonary Artery Coupling in Patients Undergoing Transcatheter Tricuspid Valve Intervention".

BACKGROUND Right ventricular to pulmonary artery (RV-PA) coupling has been established as a prognostic marker in patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve interventions (TTVI). RV-PA coupling assesses right ventricular systolic function related to pulmonary artery pressure levels, which are ideally measured by right heart catheterization. This study aims to improve the RV-PA coupling concept by relating tricuspid annular plane systolic excursion (TAPSE) to mean pulmonary artery pressure (mPAP) levels. Moreover, instead of right heart catheterization, this study sought to employ an extreme gradient boosting (XGB) algorithm to predict mPAP levels based on standard echocardiographic parameters. METHODS AND RESULTS This multicenter study included 737 patients undergoing TTVI for severe TR; among them, 55 patients from one institution served for external validation. Complete echocardiography and right heart catheterization data were available from all patients. The XGB algorithm trained on 10 echocardiographic parameters could reliably predict mPAP levels as evaluated on right heart catheterization data from external validation (Pearson correlation coefficient R: 0.68; p-value: 1.3x10-8). Moreover, predicted mPAP (mPAPpredicted) levels were superior to echocardiographic systolic pulmonary artery pressure (sPAPechocardiography) levels in predicting 2-year mortality after TTVI (area under the curve [AUC]: 0.607 vs. 0.520; p-value: 1.9x10-6). Furthermore, TAPSE/mPAPpredicted was superior to TAPSE/sPAPechocardiography in predicting 2-year mortality after TTVI (AUC: 0.633 vs. 0.586; p-value: 0.008). Finally, patients with preserved RV-PA coupling (defined as TAPSE/mPAPpredicted > 0.617 mm/mmHg) showed significantly higher 2-year survival rates after TTVI than patients with reduced RV-PA coupling (81.5% vs. 58.8%, p-value: < 0.001). Moreover, independent association between TAPSE/mPAPpredicted levels and 2-year mortality after TTVI was confirmed by multivariate regression analysis (p-value: 6.3x10-4). CONCLUSIONS Artificial intelligence-enabled RV-PA coupling assessment can refine risk stratification prior to TTVI without necessitating invasive right heart catheterization. A comparison with conservatively treated patients is mandatory to quantify the benefit of TTVI in accordance with RV-PA coupling

Epiphenomenon or prognostically relevant interventional target?

$\bf BACKGROUND:$ Tricuspid regurgitation (TR) frequently develops in patients with long-standing pulmonary hypertension, and both pathologies are associated with increased morbidity and mortality. This study aimed to improve prognostic assessment in patients with severe TR undergoing transcatheter tricuspid valve intervention (TTVI) by relating the extent of TR to pulmonary artery pressures. $\textbf {METHODS AND RESULTS:}$ In this multicenter study, we included 533 patients undergoing TTVI for moderate-to-severe or severe TR. The proportionality framework was based on the ratio of tricuspid valve effective regurgitant orifice area to mean pulmonary artery pressure. An optimal threshold for tricuspid valve effective regurgitant orifice area/mean pulmonary artery pressure ratio was derived on 353 patients with regard to 2-year all-cause mortality and externally validated on 180 patients. Patients with a tricuspid valve effective regurgitant orifice area/mean pulmonary artery pressure ratio $\leq$1.25$mm^{2}$/mmHg (defining proportionate TR) featured significantly lower 2-year survival rates after TTVI than patients with disproportionate TR (56.6% versus 69.6%; $\it P$=0.005). In contrast with patients with disproportionate TR (n=398), patients with proportionate TR (n=135) showed more pronounced mPAP levels (37.9$\pm$9.06mmHg versus 27.9$\pm$8.17mmHg; $\it {P}<2.2×10^{−16}$) and more severely impaired right ventricular function (tricuspid annular plane systolic excursion: 16.0$\pm$4.11 versus 17.0$\pm$4.64mm; $\it P$=0.012). Moreover, tricuspid valve effective regurgitant orifice area was smaller in patients with proportionate TR when compared with disproportionate TR (0.350$\pm$0.105$cm^{2}$ versus 0.770$\pm$0.432$cm^{2}$; $\it {P}<2.2×10^{−16}$). Importantly, proportionate TR remained a significant predictor for 2-year mortality after adjusting for demographic and clinical variables (hazard ratio, 1.7; $\it P$=0.006). $\bf CONCLUSIONS:$ The proposed proportionality framework promises to improve future risk stratification and clinical decisionmaking by identifying patients who benefit the most from TTVI (disproportionate TR). As a next step, randomized controlled studies with a conservative treatment arm are needed to quantify the net benefit of TTVI in patients with proportionate TR