Monitoring of mitral- and tricuspid valve interventions with CardioMEMS: Insights beyond imaging.

BACKGROUND: Mitral- and tricuspid regurgitation are associated with significant morbidity and mortality and are increasingly treated interventionally. CardioMEMS is a transcutaneously implanted pressure sensor placed in the pulmonary artery that allows invasive measurement of pulmonary artery pressure and cardiac output. METHODS: This proof-of-concept study aimed to observe hemodynamic changes as determined by CardioMEMS after transcatheter atrioventricular valve interventions, assess the additional value of CardioMEMS on top of echocardiography, and investigate a potential effect of CardioMEMS on outcome. Patients treated with transcatheter mitral- or tricuspid valve interventions (mitral: TMVR, tricuspid: TTVR) or bicaval valve implantation (bi-CAVI) were recruited. All patients were followed for 12 months. RESULTS: Thirty-six patients were included (4 with CardioMEMS, 32 controls). Patients with CardioMEMS were monitored prior to intervention and 3-12 months thereafter (one received TMVR, one bi-CAVI, one both TMVR and TTVR, and one isolated TTVR). CardioMEMS group: In both patients with TMVR and in the patient with bi-CAVI, mean pulmonary artery pressures decreased (all p < .001) and cardiac output increased significantly (both TMVR p < .001 and bi-CAVI p = .006) while functional parameters, echocardiography, and NT-proBNP were difficult to interpret, unreliable, or both. Changes after TTVR remained inconclusive. CONCLUSION: Invasive monitoring using CardioMEMS provides important information after mitral- and tricuspid valve interventions. Such data pave the way for a deeper understanding of the prerequisites for optimal patient selection and management for catheter-based interventions.

Plasma Small Extracellular Vesicle Cardiac miRNA Expression in Patients with Ischemic Heart Failure, Randomized to Percutaneous Intramyocardial Treatment of Adipose Derived Stem Cells or Placebo: Subanalysis of the SCIENCE Study.

Small extracellular vesicles (EVs) and their cargo are an important component of cell-to-cell communication in cardiac disease. Allogeneic adipose derived stem cells (ADSCs) are thought to be a potential approach for cardiac regenerative therapy in ischemic heart disease. The SCIENCE study investigated the effect of ADSCs administered via intramyocardial injection on cardiac function in patients with ischemic heart disease. The aim of this substudy, based on samples from 15 patients, was to explore small EV miRNA dynamics after treatment with ADSCs compared to a placebo. Small EVs were isolated at several timepoints after the percutaneous intramyocardial application of ADSCs. No significant effect of ADSC treatment on small EV concentration was detected. After 12 months, the expression of miR-126 decreased significantly in ADSC patients, but not in the placebo-treated group. However, all cardiac miRNAs correlated with plasma cardiac biomarkers. In line with the overall negative results of the SCIENCE study, with the exception of one miR, we did not detect any significant regulation of small EV miRNAs in this patient collective.

Bioimpedance Spectroscopy Reveals Important Association of Fluid Status and T1 -Mapping by Cardiovascular Magnetic Resonance.

BACKGROUND: Extracellular matrix expansion is a key pathophysiologic feature in heart failure and can be quantified noninvasively by cardiac magnetic resonance T1 -mapping. Free water within the interstitial space of the myocardium, however, may also alter T1 -mapping results. PURPOSE: To investigate the association between systemic fluid status and T1 -mapping by cardiac magnetic resonance. STUDY TYPE: Prospective, observational single-center study. POPULATION: Two-hundred eighty-five consecutive patients (44.4% female, 70.0 ± 14.9 years old) scheduled for cardiac MR due to various cardiac diseases. SEQUENCE AND FIELD STRENGTH: 1.5-T scanner (Avanto Fit, Siemens Healthineers, Erlangen, Germany). For T1 -mapping, electrocardiographically triggered modified-Look-Locker inversion (MOLLI) recovery sequence using a 5(3)3 prototype on a short-axis mid-cavity slice and with a four-chamber view was performed. ASSESSMENTS: MR parameters including native myocardial T1 -times using MOLLI and extracellular volume (MR-ECV) were assessed, and additionally, we performed bioimpedance analysis (BIA). Furthermore, demographic data and comorbidities were assessed. STATISTICS: Wilcoxon's rank-sum test, chi-square tests, and for correlation analysis, Pearson's correlation coefficients were used. Regression analyses were performed to investigate the association between patients' fluid status and T1 -mapping results. A P-value <0.05 was considered statistically significant. RESULTS: The mixed cohort presented with a mean overhydration (OH) of +0.2 ± 2.4 liters, as determined by BIA. By MR, native T1 -times were 1038 ± 51 msec and MR-ECV was 31 ± 9%. In the multivariable regression analysis, only OH was significantly associated with MR-ECV (adj. beta: 0.711; 95% CI: 0.28 to 1.14) along with male sex (adj. beta: 2.529; 95% CI: 0.51 to 4.55). In linear as well as multivariable analysis, only OH was significantly associated with native T1 times (adj. beta: 3.750; 95% CI: 1.27 to 6.23). CONCLUSION: T1 -times and MR-ECV were significantly associated with the degree of OH on BIA measurement. These effects were independent from age, sex, body mass index, and hematocrit. Patients' volume status may thus be an important factor when T1 -time and MR-ECV values are interpreted. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Tricuspid edge-to-edge repair for tricuspid valve prolapse and flail leaflet: feasibility in comparison to patients with secondary tricuspid regurgitation.

AIMS: Transcatheter tricuspid edge-to-edge repair (T-TEER) has gained widespread use for the treatment of tricuspid regurgitation (TR) in symptomatic patients with high operative risk. Although secondary TR is the most common pathology, some patients exhibit primary or predominantly primary TR. Characterization of patients with these pathologies in the T-TEER context has not been systematically performed. METHODS AND RESULTS: Patients assigned to T-TEER by the interdisciplinary heart team were consecutively recruited in two European centres over 4 years. Echocardiographic images were evaluated to distinguish between primary and secondary causes of TR. Both groups were compared concerning procedural results. A total of 339 patients were recruited, 13% with primary TR and 87% with secondary TR. Patients with primary TR had a smaller right ventricle (basal diameter 45 vs. 49 mm, P = 0.004), a better right ventricular function (fractional area change 45 vs. 41%, P = 0.001), a smaller right (28 vs. 34 cm2, P = 0.021) and left (52 vs. 67 mL/m2, P = 0.038) atrium, and a better left ventricular ejection fraction (60 vs. 52%, P = 0.005). The severity of TR was similar in primary and secondary TR at baseline (TR vena contracta width pre-interventional 13 ± 4 vs. 14 ± 5 mm, P = 0.19), and T-TEER significantly reduced TR in both groups (TR vena contracta width post-interventional 4 ± 3 vs. 5 ± 5 mm, P = 0.10). These findings remained stable after propensity score matching. Complications were similar between both groups. CONCLUSION: T-TEER confers equally safe and effective reduction of TR in patients with primary and secondary TR.

Annular remodelling predicts outcome in isolated severe tricuspid regurgitation: a registry-based echocardiographic analysis.

AIMS: Depending on volume status, secondary tricuspid regurgitation (sTR) has a strong dynamic component. In contrast, associated structural dilatation of the tricuspid annulus and the right heart chambers may be less volume dependent. This study aimed to assess the prognostic value of right heart remodelling in isolated severe sTR (isoTR). METHODS AND RESULTS: A total of 36 000 patients from the longitudinal echocardiographic database of our tertiary centre were screened for severe isoTR [vena contracta (VC) ≥ 7 mm] in the absence of atrial fibrillation (AF), other valve disease, and/or reduced systolic left ventricular function. Echocardiographic examinations were re-read, focusing on right ventricular (RV) parameters and on quantitative and qualitative parameters of isoTR. All-cause mortality was defined as the primary endpoint. Two hundred and sixteen patients fulfilled the inclusion criteria. Severe TR was predominant; only few were classified in the new grades massive [n = 23 (10%)] and torrential TR [n = 4 (2%)]. During a median follow-up of 35 months (20-53), all-cause mortality was 31% (n = 67). Multivariate Cox regression analysis revealed no association of VC, effective regurgitant orifice area, or regurgitant volume with all-cause mortality. However, indexed RV end-diastolic diameter (P < 0.001), indexed right atrial dimensions (P = 0.019), and particularly tricuspid valve (TV) annulus diameter diastole index (P = 0.002) and TV annulus diameter systole index (P = 0.001) were significantly associated with outcome. CONCLUSION: Severe isolated TR in the absence of AF is a rare finding with a grim prognosis. Tricuspid annular diameter dimensions rather than quantitative measures of TR proved to be of significant prognostic value indicating a continuous remodelling leading to a 'point of no return' with a dismal outcome.

Efficacy and safety of the Aria pulmonary endovascular device in pulmonary hypertension.

AIMS: A common feature of various forms of pulmonary hypertension (PH) is progressive decline of pulmonary arterial compliance (CPA), which correlates with reduced survival. In this acute study, we evaluated feasibility, safety and haemodynamic performance of the Aria pulmonary endovascular device in patients with PH associated with left heart disease (PH-LHD) and chronic lung disease (PH-CLD). METHODS AND RESULTS: Eight patients with PH-LHD and 10 patients with PH-CLD were included in this study. The device was placed in the main pulmonary artery via the right femoral vein and was connected by a catheter to a gas-filled reservoir outside the body. During systole, gas shifts from the balloon to the reservoir, leading to deflation of the balloon. In diastole, the gas returns from the reservoir to the balloon, leading to balloon inflation and enhancing diastolic blood flow to the distal pulmonary capillary bed. Haemodynamics were assessed at baseline, and again with device off, device on and device off. The primary safety endpoint was the incidence of serious adverse events through 30 days after the procedure. No complications or investigational device-related serious adverse events occurred. Device activation in PH-LHD and PH-CLD patients decreased pulmonary arterial pulse pressure by 5.6 ± 4.2 mmHg (-12%; p = 0.003) and 4.2 ± 2.2 mmHg (-11%; p < 0.001), increased CPA by 0.4 ± 0.2 ml/mmHg (+23%; p = 0.004) and 0.4 ± 0.3 ml/mmHg (+25%; p = 0.001), and increased right ventricular-to-pulmonary vascular (RV-PV) coupling by 0.24 ± 0.18 (+40%; p = 0.012) and 0.11 ± 0.07 (+21%; p = 0.001), respectively. CONCLUSIONS: Temporary implantation of the Aria endovascular device was feasible and safe. Device activation resulted in acute improvement of CPA and RV-PV coupling.

Lower free triiodothyronine (fT3) levels in cirrhosis are linked to systemic inflammation, higher risk of acute-on-chronic liver failure, and mortality.

Background & Aims: Advanced chronic liver disease (ACLD) may affect thyroid hormone homeostasis. We aimed to analyze the pituitary-thyroid axis in ACLD and the prognostic value of free triiodothyronine (fT3). Methods: Patients with ACLD (liver stiffness measurement [LSM] ≥10 kPa) undergoing hepatic venous pressure gradient (HVPG) measurement between June 2009 and September 2022 and available fT3 levels were included. Clinical stages of ACLD were defined as follows: probable ACLD (pACLD; LSM ≥10 kPa and HVPG ≤5 mmHg), S0 (mild portal hypertension [PH]; HVPG 6-9 mmHg), S1 (clinically significant PH), S2 (clinically significant PH with varices), S3 (past variceal bleeding), S4 (past/current non-bleeding hepatic decompensation), and S5 (further decompensation). Results: Among 297 patients with ACLD, 129 were compensated (pACLD, n = 10; S0, n = 33; S1, n = 42; S2, n = 44), whereas 168 were decompensated (S3, n = 12; S4, n = 97; S5, n = 59). Median levels of thyroid-stimulating hormone (TSH) numerically increased with progressive ACLD stage (from 1.2 µIU/ml [pACLD] to 1.5 µIU/ml [S5]; p = 0.152), whereas fT3 decreased (from 3.2 pg/ml [pACLD] to 2.5 pg/ml [S5]; p <0.001). Free thyroxin levels remained unchanged (p = 0.338). TSH (aB 0.45; p = 0.046) and fT3 (aB -0.17; p = 0.048) were independently associated with systemic C-reactive protein levels. Lower fT3 was linked to higher risk of (further) decompensation (adjusted subdistribution hazard ratio [asHR] 0.60; 95% CI 0.37-0.97; p = 0.037), acute-on-chronic liver failure (asHR 0.19; 95% CI 0.08-0.49; p <0.001) and liver-related death (asHR 0.14; 95% CI 0.04-0.51; p = 0.003). Conclusions: Increasing TSH and declining fT3 levels are observed with progressive ACLD stages. The association of TSH and fT3 with systemic inflammation suggests a liver disease-associated non-thyroidal illness syndrome. Lower fT3 levels in patients with ACLD indicate increased risk for decompensation, acute-on-chronic liver failure, and liver-related death. Impact and Implications: In a large well-characterized cohort of patients with advanced chronic liver disease (ACLD), we found a decline of free triiodothyronine (fT3) throughout the clinical stages of ACLD, paralleled by a numerical increase of thyroid-stimulating hormone (TSH). This suggests a progressive development of a non-thyroidal illness syndrome in association with ACLD severity. Importantly, C-reactive protein independently correlated with TSH and fT3, linking thyroid dysbalance in ACLD to systemic inflammation. Lower fT3 indicated an increased risk for subsequent development of hepatic decompensation, acute-on-chronic liver failure, and liver-related death. Clinical trial number: Vienna Cirrhosis Study (VICIS; NCT: NCT03267615).

Mixed aortic valve disease: association with paravalvular leak and reduced survival after transcatheter aortic valve replacement.

AIMS: Transcatheter aortic valve replacement (TAVR) revolutionized the therapy of severe aortic stenosis (AS) with rising numbers. Mixed aortic valve disease (MAVD) treated by TAVR is gaining more interest, as those patients represent a more complex cohort as compared with isolated AS. However, concerning long-term outcome for this cohort only, limited data are available. The aim of the study is to assess the prevalence of MAVD in TAVR patients, investigate its association with paravalvular regurgitation (PVR), and analyse its impact on long-term mortality after TAVR. METHODS AND RESULTS: We conducted a registry-based cohort study using the Vienna TAVR registry, enrolling patients who underwent TAVR at Medical University of Vienna between January 2007 and May 2020 with available transthoracic echocardiography before and after TAVR (n = 880). Data analysis included PVR incidence and long-term survival outcomes. A total of 647 (73.52%) out of 880 patients had ≥ mild aortic regurgitation next to severe AS. MAVD was associated with PVR compared with isolated AS with an odds ratio of 2.06, 95% confidence interval (CI): 1.51-2.81 (P = <0.001). More than mild PVR after TAVR (n = 168 out of 880: 19.09%) was related to higher mortality compared with the absence of PVR with a hazard ratio (HR) of 1.33, 95% CI: 1.05- 1.67 (P = 0.016). MAVD patients developing ≥ mild PVR after TAVR were also associated with higher mortality compared with the absence of PVR with an HR of 1.30 and 95% CI: 1.04-1.62 (P = 0.022). CONCLUSION: MAVD is prevalent among TAVR patients and presents unique challenges, with increased PVR risk and worse outcomes compared with isolated AS. Long-term survival for MAVD patients, not limited to those developing PVR post-TAVR, is compromised. Earlier intervention before the occurrence of structural myocardial damage or surgical valve replacement might be a potential workaround to improve outcomes.

Left Ventricular Filling Pressure in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of major pulmonary arteries with organized thrombi. Clinical risk factors for pulmonary hypertension due to left heart disease including metabolic syndrome, left-sided valvular heart disease, and ischemic heart disease are common in CTEPH patients. OBJECTIVES: The authors sought to investigate prevalence and prognostic implications of elevated left ventricular filling pressures (LVFP) in CTEPH. METHODS: A total of 593 consecutive CTEPH patients undergoing a first diagnostic right and left heart catheterization were included in this study. Mean pulmonary arterial wedge pressure (mPAWP) and left ventricular end-diastolic pressure (LVEDP) were utilized for assessment of LVFP. Two cutoffs were applied to identify patients with elevated LVFP: 1) for the primary analysis mPAWP and/or LVEDP >15 mm Hg, as recommended by the current pulmonary hypertension guidelines; and 2) for the secondary analysis mPAWP and/or LVEDP >11 mm Hg, representing the upper limit of normal. Clinical and echocardiographic features, and long-term mortality were assessed. RESULTS: LVFP was >15 mm Hg in 63 (10.6%) and >11 mm Hg in 222 patients (37.4%). Univariable logistic regression analysis identified age, systemic hypertension, diabetes, atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume as significant predictors of elevated LVFP. Atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume remained independent determinants of LVFP in adjusted analysis. At follow-up, higher LVFPs were measured in patients who had meanwhile undergone pulmonary endarterectomy (P = 0.002). LVFP >15 mm Hg (P = 0.021) and >11 mm Hg (P = 0.006) were both associated with worse long-term survival. CONCLUSIONS: Elevated LVFP is common, appears to be due to comorbid left heart disease, and predicts prognosis in CTEPH.

Incidence, causes, correlates, and outcome of bioprosthetic valve dysfunction and failure following transcatheter aortic valve implantation.

AIMS: Bioprosthetic valve dysfunction (BVD) is a major concern regarding transcatheter aortic valve implantation (TAVI) durability. We aimed to assess incidence, correlates, causes, and outcome of early to mid-term BVD after TAVI in relation to patient's life expectancy. METHODS AND RESULTS: Consecutive TAVI recipients (2007-20) with a follow-up ≥1 year were prospectively included. BVD and bioprosthetic valve failure (BVF) were assessed according to Valve-Academic-Research-Consortium-3. BVD/BVF and all-cause death served as endpoints. Average life expectancy was calculated from National Open Health Data and patients were stratified according to tertiles (1st: <6.85 years, 2nd: 6.85-9.7 years, 3rd: >9.7 years). Of 1047 patients (81.6 ± 6.8 years old, EuroSCORE II 4.5 ± 2.5), ≥2 follow ups were available from 622 (serial echo cohort). After a median echo follow up of 12.2 months, incidence rates of BVD/BVF were 8.4% (95% confidence interval 6.7-10.3), and 3.5% (2.5-4.9) per valve-year, respectively, without differences between life expectancy tertiles. The incidence of BVD was two-fold higher within the first year of implant (9.9% per valve-year) vs. beyond (4.8% per valve-year). Valve-in-valve procedure and residual stenosis, but not age/life expectancy predisposed for BVD. BVD/BVF were independently associated with outcome for patients in the first [adjusted hazard ratio (AHR) 1.72 (1.06-2.88)/2.97 (1.72-6.22)] and second [AHR 1.96 (1.02-3.73)/2.31 (1.00-5.30)], but not the third tertile of life expectancy (P = n.s.). CONCLUSIONS: In this large prospective observational cohort, early to mid-term BVD after TAVI occurred at the same rate across the spectrum of life expectancy and was associated with increased mortality in patients with short but not in those with the longest life expectancy.

Impact of right ventricular-to-pulmonary artery coupling on remodeling and outcome in patients undergoing transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Right ventricular-to-pulmonary artery (RV-PA) coupling has recently been shown to be associated with outcome in valvular heart disease. However, longitudinal data on RV dysfunction and reverse cardiac remodeling in patients following transcatheter edge-to-edge mitral valve repair (M-TEER) are scarce. METHODS: Consecutive patients with primary as well as secondary mitral regurgitation (MR) were prospectively enrolled and had comprehensive echocardiographic and invasive hemodynamic assessment at baseline. Kaplan-Meier estimates and multivariable Cox-regression analyses were performed, using a composite endpoint of heart failure hospitalization and death. RESULTS: Between April 2018 and January 2021, 156 patients (median 78 y/o, 55% female, EuroSCORE II: 6.9%) underwent M-TEER. On presentation, 64% showed impaired RV-PA coupling defined as tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio < 0.36. Event-free survival rates at 2 years were significantly lower among patients with impaired coupling (57 vs. 82%, p < 0.001), both in patients with primary (64 vs. 91%, p = 0.009) and secondary MR (54 vs. 76%, p = 0.026). On multivariable Cox-regression analyses adjusted for baseline, imaging, hemodynamic, and procedural data, TAPSE/PASP ratio < 0.36 was independently associated with outcome (adj.HR 2.74, 95% CI 1.17-6.43, p = 0.021). At 1-year follow-up, RV-PA coupling improved (TAPSE: ∆ + 3 mm, PASP: ∆ - 10 mmHg, p for both < 0.001), alongside with a reduction in tricuspid regurgitation (TR) severity (grade ≥ II: 77-54%, p < 0.001). CONCLUSIONS: TAPSE/PASP ratio was associated with outcome in patients undergoing M-TEER for primary as well as secondary MR. RV-PA coupling, alongside with TR severity, improved after M-TEER and might thus provide prognostic information in addition to established markers of poor outcome.

A streamlined, machine learning-derived approach to risk-stratification in heart failure patients with secondary tricuspid regurgitation.

AIMS: Secondary tricuspid regurgitation (sTR) is the most frequent valvular heart disease and has a significant impact on mortality. A high burden of comorbidities often worsens the already dismal prognosis of sTR, while tricuspid interventions remain underused and initiated too late. The aim was to examine the most powerful predictors of all-cause mortality in moderate and severe sTR using machine learning techniques and to provide a streamlined approach to risk-stratification using readily available clinical, echocardiographic and laboratory parameters. METHODS AND RESULTS: This large-scale, long-term observational study included 3359 moderate and 1509 severe sTR patients encompassing the entire heart failure spectrum (preserved, mid-range and reduced ejection fraction). A random survival forest was applied to investigate the most important predictors and group patients according to their number of adverse features.The identified predictors and thresholds, that were associated with significantly worse mortality were lower glomerular filtration rate (<60 mL/min/1.73m2), higher NT-proBNP, increased high sensitivity C-reactive protein, serum albumin < 40 g/L and hemoglobin < 13 g/dL. Additionally, grouping patients according to the number of adverse features yielded important prognostic information, as patients with 4 or 5 adverse features had a fourfold risk increase in moderate sTR [4.81(3.56-6.50) HR 95%CI, P < 0.001] and fivefold risk increase in severe sTR [5.33 (3.28-8.66) HR 95%CI, P < 0.001]. CONCLUSION: This study presents a streamlined, machine learning-derived and internally validated approach to risk-stratification in patients with moderate and severe sTR, that adds important prognostic information to aid clinical-decision-making.

Quantitative fluid overload in severe aortic stenosis refines cardiac damage and associates with worse outcomes.

AIMS: Cardiac decompensation in aortic stenosis (AS) involves extra-valvular cardiac damage and progressive fluid overload (FO). FO can be objectively quantified using bioimpedance spectroscopy. We aimed to assess the prognostic value of FO beyond established damage markers to guide risk stratification. METHODS AND RESULTS: Consecutive patients with severe AS scheduled for transcatheter aortic valve implantation (TAVI) underwent prospective risk assessment with bioimpedance spectroscopy (BIS) and echocardiography. FO by BIS was defined as ≥1.0 L (0.0 L = euvolaemia). The extent of cardiac damage was assessed by echocardiography according to an established staging classification. Right-sided cardiac damage (rCD) was defined as pulmonary vasculature/tricuspid/right ventricular damage. Hospitalization for heart failure (HHF) and/or death served as primary endpoint. In total, 880 patients (81 ± 7 years, 47% female) undergoing TAVI were included and 360 (41%) had FO. Clinical examination in patients with FO was unremarkable for congestion signs in >50%. A quarter had FO but no rCD (FO+/rCD-). FO+/rCD+ had the highest damage markers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. After 2.4 ± 1.0 years of follow-up, 236 patients (27%) had reached the primary endpoint (29 HHF, 194 deaths, 13 both). Quantitatively, every 1.0 L increase in bioimpedance was associated with a 13% increase in event hazard (adjusted hazard ratio 1.13, 95% confidence interval 1.06-1.22, p < 0.001). FO provided incremental prognostic value to traditional risk markers (NT-proBNP, EuroSCORE II, damage on echocardiography). Stratification according to FO and rCD yielded worse outcomes for FO+/rCD+ and FO+/rCD-, but not FO-/rCD+, compared to FO-/rCD-. CONCLUSION: Quantitative FO in patients with severe AS improves risk prediction of worse post-interventional outcomes compared to traditional risk assessment.

Contemporary insights into the epidemiology, impact and treatment of secondary tricuspid regurgitation across the heart failure spectrum.

AIM: Tricuspid regurgitation secondary to heart failure (HF) is common with considerable impact on survival and hospitalization rates. Currently, insights into epidemiology, impact, and treatment of secondary tricuspid regurgitation (sTR) across the entire HF spectrum are lacking, yet are necessary for healthcare decision-making. METHODS AND RESULTS: This population-based study included data from 13 469 patients with HF and sTR from the Viennese community over a 10-year period. The primary outcome was long-term mortality. Overall, HF with preserved ejection fraction was the most frequent (57%, n = 7733) HF subtype and the burden of comorbidities was high. Severe sTR was present in 1514 patients (11%), most common among patients with HF with reduced ejection fraction (20%, n = 496). Mortality of patients with sTR was higher than expected survival of sex- and age-matched community and independent of HF subtype (moderate sTR: hazard ratio [HR] 6.32, 95% confidence interval [CI] 5.88-6.80, p < 0.001; severe sTR: HR 9.04; 95% CI 8.27-9.87, p < 0.001). In comparison to HF and no/mild sTR patients, mortality increased for moderate sTR (HR 1.58, 95% CI 1.48-1.69, p < 0.001) and for severe sTR (HR 2.19, 95% CI 2.01-2.38, p < 0.001). This effect prevailed after multivariate adjustment and was similar across all HF subtypes. In subgroup analysis, severe sTR mortality risk was more pronounced in younger patients (<70 years). Moderate and severe sTR were rarely treated (3%, n = 147), despite availability of state-of-the-art facilities and universal health care. CONCLUSION: Secondary tricuspid regurgitation is frequent, increasing with age and associated with excess mortality independent of HF subtype. Nevertheless, sTR is rarely treated surgically or percutaneously. With the projected increase in HF prevalence and population ageing, the data suggest a major burden for healthcare systems that needs to be adequately addressed. Low-risk transcatheter treatment options may provide a suitable alternative.

Case Report: Residual Atrial Shunt Lesions in Aging Adults With Congenital Heart Disease: An Underestimated Risk of Stroke?

We report two cases of paradoxical cerebral embolism in adults with congenital heart disease (ACHD) with residual atrial shunt lesions, a 59 year-old male patient with partial detachment of a surgical ASD closure patch, and a 57 year-old male patient with Ebstein's anomaly and a large patent foramen ovale. Considering these mechanisms and the increasing incidence of venous thrombosis with age, a higher prevalence of paradoxical embolism in ACHD patients with residual atrial shunts may be suspected. Regular follow-up of patients with ACHD remains important throughout life even in seemingly stable lesions.

Severe tricuspid regurgitation: prognostic role of right heart remodelling and pulmonary hypertension.

AIMS: Left heart diseases (LHDs) are the main driving forces for the development of functional tricuspid regurgitation (TR). Therefore, in most cases, the true prognostic value of TR remains concealed by concomitant LHD. This study aimed to analyse right heart remodelling in patients with TR without other valve disease and with normal systolic left ventricular function (sysLVF), and to stratify its prognostic value in the presence (dPH, maximal TR velocity signal (TRVmax) ≥ 3.5 m/s in echocardiography) or absence (nsPH, TRVmax < 3.5m/s) of concomitant pulmonary hypertension (PH). METHODS AND RESULTS: We performed an observational analysis of all patients diagnosed with TR in the absence of other valve disease and reduced sysLVF at our institution between 1 January 2003 and 31 December 2013. Five-year mortality was chosen as endpoint. The final cohort entailed 29 979 consecutive patients (median age 60 years, interquartile range 46-70), 49.9% were male, mean follow-up was 95±49 months. Severe TR was present in 790 patients (2.6%). In dPH and in nsPH, severe TR was associated with an excess 5-year mortality that was even more pronounced in the dPH group (58.2% vs. 43.6%, P = 0.001). In nsPH, right ventricular dysfunction predicted mortality. In dPH, mortality was independent of presence or absence of right heart dilatation or dysfunction. CONCLUSION: Severe TR without concomitant left heart valve disease or LV systolic dysfunction was a rare disease in this large-scale all-comer population and is associated with an unfavourable prognosis. The differentiation of patients with nsPH and dPH is essential as they present with different patterns of right heart remodelling and with different long-time outcomes.

Prevalence and Outcomes of Cardiac Amyloidosis in All-Comer Referrals for Bone Scintigraphy.

The prevalence of cardiac amyloidosis (CA) in the general population and associated prognostic implications remain poorly understood. We aimed to identify CA prevalence and outcomes in bone scintigraphy referrals. Methods: Consecutive all-comers undergoing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic-acid (99mTc-DPD) bone scintigraphy between 2010 and 2020 were included. Perugini grade 1 was defined as low-grade uptake and grade 2 or 3 as confirmed CA. All-cause mortality, cardiovascular death, and heart failure hospitalization (HHF) served as endpoints. Results: In total, 17,387 scans from 11,527 subjects (age, 61 ± 16 y; 63.0% women, 73.6% cancer) were analyzed. Prevalence of 99mTc-DPD positivity was 3.3% (n = 376/11,527; grade 1: 1.8%, grade 2 or 3: 1.5%), and was higher among cardiac than noncardiac referrals (18.2% vs. 1.7%). In individuals with more than 1 scan, progression from grade 1 to grade 2 or 3 was observed. Among patients with biopsy-proven CA, the portion of light-chain (AL)-CA was significantly higher in grade 1 than grade 2 or 3 (73.3% vs. 15.4%). After a median of 6 y, clinical event rates were: 29.4% mortality, 2.6% cardiovascular death, and 1.5% HHF, all independently predicted by positive 99mTc-DPD. Overall, adverse outcomes were driven by confirmed CA (vs. grade 0, mortality: adjusted hazard ratio [AHR] 1.46 [95% CI 1.12-1.90]; cardiovascular death: AHR 2.34 [95% CI 1.49-3.68]; HHF: AHR 2.25 [95% CI 1.51-3.37]). One-year mortality was substantially higher in cancer than noncancer patients. Among noncancer patients, also grade 1 had worse outcomes than grade 0 (HHF/death: AHR 1.45 [95% CI 1.01-2.09]), presumably because of longer observation and higher prognostic impact of early infiltration. Conclusion: Positive 99mTc-DPD was identified in a substantial number of consecutive 99mTc-DPD referrals and associated with adverse outcomes.

Transcatheter Versus Surgical Valve Repair in Patients with Severe Mitral Regurgitation.

BACKGROUND: Transcatheter edge-to-edge mitral valve repair (TMVR) is increasingly performed. However, its efficacy in comparison with surgical MV treatment (SMV) is unknown. METHODS: Consecutive patients with severe mitral regurgitation (MR) undergoing TMVR (68% functional, 32% degenerative) or SMV (9% functional, 91% degenerative) were enrolled. To account for differences in baseline characteristics, propensity score matching was performed, including age, EuroSCORE-II, left ventricular ejection fraction, and NT-proBNP. A composite of heart failure (HF) hospitalization/death served as primary endpoint. Kaplan-Meier curves and Cox-regression analyses were used to investigate associations between baseline, imaging, and procedural parameters and outcome. RESULTS: Between July 2017 and April 2020, 245 patients were enrolled, of whom 102 patients could be adequately matched (73 y/o, 61% females, EuroSCORE-II: 5.7%, p > 0.05 for all). Despite matching, TMVR patients had more co-morbidities at baseline (higher rates of prior myocardial infarction, coronary revascularization, pacemakers/defibrillators, and diabetes mellitus, p < 0.009 for all). Patients were followed for 28.3 ± 27.2 months, during which 27 events (17 deaths, 10 HF hospitalizations) occurred. Postprocedural MR reduction (MR grade <2: TMVR vs. SMV: 88% vs. 94%, p = 0.487) and freedom from HF hospitalization/death (log-rank: p = 0.811) were similar at 2 years. On multivariable Cox analysis, EuroSCORE-II (adj.HR 1.07 [95%CI: 1.00-1.13], p = 0.027) and residual MR (adj.HR 1.85 [95%CI: 1.17-2.92], p = 0.009) remained significantly associated with outcome. CONCLUSIONS: In this propensity-matched, all-comers cohort, two-year outcomes after TMVR versus SMV were similar. Given the reported favorable long-term durability of TMVR, the interventional approach emerges as a valuable alternative for a substantial number of patients with functional and degenerative MR.

Tailored Risk Stratification in Severe Mitral Regurgitation and Heart Failure Using Supervised Learning Techniques.

Background: Secondary mitral regurgitation (sMR) in the setting of heart failure (HF) has considerable impact on quality of life, HF rehospitalizations, and mortality. Identification of high-risk cohorts is essential to understand disease trajectories and for risk stratification. Objectives: This study aimed to provide a structured decision tree-like approach to risk stratification in patients with severe sMR and HF. Methods: This observational study included 1,317 patients with severe sMR from the entire HF spectrum. Clinical, echocardiographic, and laboratory data were extracted for all patients. The primary end point was all-cause mortality. Survival tree analysis, a supervised learning technique, was applied to identify patient subgroups at risk of mortality and further stratified by HF subtype (preserved, mildly reduced, and reduced ejection fraction). Results: Using supervised learning (survival tree method), 8 distinct subgroups were identified that differed significantly in long-term survival. Subgroup 7, characterized by younger age (≤66 years), higher hemoglobin (>12.7 g/dL), and higher albumin levels (>40.6 g/L) had the best survival. In contrast, subgroup 5 displayed a 20-fold risk of mortality (hazard ratio: 20.38 [95% CI: 10.78-38.52]); P < 0.001 and had older age (>68 years), low serum albumin (≤40.6 g/L), and higher NT-proBNP levels (≥9,750 pg/mL). Unique subgroups were further identified for each type of HF subtypes. Conclusions: Supervised machine learning reveals heterogeneity in the sMR risk spectrum, highlighting the clinical variability in the population. A decision tree-like model can help identify differences in outcomes among subgroups and can help provide tailored risk stratification.

Invasive Hemodynamic Assessment and Procedural Success of Transcatheter Tricuspid Valve Repair-Important Factors for Right Ventricular Remodeling and Outcome.

Introduction: Severe tricuspid regurgitation (TR) is a common condition promoting right heart failure and is associated with a poor long-term prognosis. Transcatheter tricuspid valve repair (TTVR) emerged as a low-risk alternative to surgical repair techniques. However, patient selection remains controversial, particularly regarding the benefits of TTVR in patients with pulmonary hypertension (PH). Aim: We aimed to investigate the impact of preprocedural invasive hemodynamic assessment and procedural success on right ventricular (RV) remodeling and outcome. Methods: All patients undergoing TTVR with a TR reduction of ≥1 grade without precapillary or combined PH [mean pulmonary artery pressure (mPAP) ≥25 mmHg, mean pulmonary artery Wedge pressure ≤ 15 mmHg, pulmonary vascular resistance ≥3 Wood units] were assigned to the responder group. All patients with a TR reduction of ≥1 grade and precapillary or combined PH were classified as non-responders. Patients with a TR reduction ≥2 grade were directly classified as responders, and patients without TR reduction were directly assigned as non-responders. Results: A total of 107 patients were enrolled, 75 were classified as responders and 32 as non-responders. We observed evidence of significant RV reverse remodeling in responders with a decrease in RV diameters (-2.9 mm, p = 0.001) at a mean follow-up of 229 days (±219 SD) after TTVR. RV function improved in responders [fractional area change (FAC) + 5.7%, p < 0.001, RV free wall strain +3.9%, p = 0.006], but interestingly further deteriorated in non-responders (FAC -4.5%, p = 0.003, RV free wall strain -3.9%, p = 0.007). Non-responders had more persistent symptoms than responders (NYHA ≥3, 72% vs. 11% at follow-up). Subsequently, non-response was associated with a poor long-term prognosis in terms of death, heart failure (HF) hospitalization, and re-intervention after 2 years (freedom of death, HF hospitalization, and reintervention at 2 years: 16% vs. 78%, log-rank: p < 0.001). Conclusion: Hemodynamic assessment before TTVR and procedural success are significant factors for patient prognosis. The hemodynamic profiling prior to intervention is an essential component in patient selection for TTVR. The window for edge-to-edge TTVR might be limited, but timely intervention is an important factor for a better outcome and successful right ventricular reverse remodeling.