Management of Fluid Overload in Patients With Severe Aortic Stenosis (EASE-TAVR): A Randomized Controlled Trial.

BACKGROUND: Fluid overload (FO) subjects patients with severe aortic stenosis (AS) to increased risk for heart failure and death after valve replacement and can be objectively quantified using bioimpedance spectroscopy (BIS). OBJECTIVES: The authors hypothesized that in AS patients with concomitant FO, BIS-guided decongestion could improve prognosis and quality of life following transcatheter aortic valve replacement (TAVR). METHODS: This randomized, controlled trial enrolled 232 patients with severe AS scheduled for TAVR. FO was defined using a portable whole-body BIS device according to previously established cutoffs (≥1.0 L and/or ≥7%). Patients with FO (n = 111) were randomly assigned 1:1 to receive BIS-guided decongestion (n = 55) or decongestion by clinical judgment alone (n = 56) following TAVR. Patients without FO (n = 121) served as a control cohort. The primary endpoint was the composite of hospitalization for heart failure and/or all-cause death at 12 months. The secondary endpoint was the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire. RESULTS: The occurrence of the primary endpoint at 12 months was significantly lower in the BIS-guided vs the non-BIS-guided decongestion group (7/55 [12.7%, all deaths] vs 18/56 [32.1%, 9 hospitalizations for heart failure and 9 deaths]; HR: 0.36; 95% CI: 0.15-0.87; absolute risk reduction = -19.4%). Outcomes in the BIS-guided decongestion group were identical to the euvolemic control group (log-rank test, P = 0.7). BIS-guided decongestion was also associated with a higher increase in the Kansas City Cardiomyopathy Questionnaire score from baseline compared to non-BIS-guided decongestion (P = 0.001). CONCLUSIONS: In patients with severe AS and concomitant FO, quantitatively guided decongestive treatment and associated intensified management post-TAVR was associated with improved outcomes and quality of life compared to decongestion by clinical judgment alone. (Management of Fluid Overload in Patients Scheduled for Transcatheter Aortic Valve Replacement [EASE-TAVR]; NCT04556123).

Low Bone Mineral Density on Computed Tomography: Association with Poor Survival after Transcatheter Aortic Valve Replacement.

Background: Transcatheter aortic valve replacement (TAVR) has evolved as first-line therapy for severe aortic valve stenosis (AS), with pre-procedural computed tomography (CT) providing critical anatomical information. While primarily used for anatomical planning, TAVR-CT also offers an opportunity to assess low bone mineral density (BMD), a known indicator of frailty. Despite this, the prognostic role of BMD in TAVR patients remains unknown. This study aimed to evaluate BMD on routine TAVR-CT and its impact on long-term survival. Methods: In this retrospective study, 770 consecutive TAVR patients (mean age 80.7 ± 6.7 years, 54.0% males) between November 2015 and March 2022 were included. BMD was measured from a single axial image at the thoracic vertebral level on unenhanced CT scans. Cox regression models assessed the impact of BMD on mortality, and Restricted Cubic Spline models identified potential mortality thresholds. Results: The mean BMD value, as measured on non-contrast CT, was 147.5 ± 5.4 Hounsfield units, demonstrating a noteworthy association with mortality (adjusted hazard ratio per 100 HU decrease: 1.27 [95%CI: 1.01-1.59], p = 0.041). Restricted cubic spline analysis indicated that BMD below 200 HU was linked to a substantial increase in mortality risk. Upon crude Cox regression analysis, every 100 HU decrease was associated with a 32% increase in risk for death (HR 1.32 [95%CI: 1.068-1.65)], p = 0.010). Conclusions: In conclusion, low BMD on TAVR-CT is independently associated with reduced survival, suggesting its potential as a tool for comprehensive frailty assessment and improved risk prediction in TAVR patients.

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.

Impact of stroke history on procedural cerebrovascular insult probability and long-term outcome after TAVI.

BACKGROUND: In TAVI procedural stroke is one of the most feared complications and for this reason also extensively studied. But there is a lack of data concerning the impact of previous stroke on procedural stroke and on long-term survival. The aim of this registry-based cohort study is to evaluate the prevalence of previous stroke in TAVI patients and its impact on procedural stroke risk as well as long-term outcome. METHODS: We included all patients treated with TAVI between January 2007 and December 2020 and investigated concerning previous stroke in their medical history. Among 958 patients, 55 patients had previous stroke and were included in the present analysis. RESULTS: The salient finding of the present study is that previous stroke is significantly associated with higher all-cause mortality and has established itself as a predictor for poor outcome after TAVI. This is also observed after adjusting for confounders like EuroSCORE II (European system for cardiac operative risk evaluation) and AF (atrial fibrillation) as one of the main underlying diseases for cerebrovascular insult (CVI). However, previous stroke is not associated with higher rates of procedural CVI. CONCLUSION: A history of stroke is significantly associated with higher all-cause mortality and has established itself as a predictor for poor outcome after TAVI without higher rates of procedural stroke.

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.

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.

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.

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.

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.

Reverse Remodeling Following Valve Replacement in Coexisting Aortic Stenosis and Transthyretin Cardiac Amyloidosis.

BACKGROUND: Dual pathology of severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR) is increasingly recognized. Evolution of symptoms, biomarkers, and myocardial mechanics in AS-ATTR following valve replacement is unknown. We aimed to characterize reverse remodeling in AS-ATTR and compared with lone AS. METHODS: Consecutive patients referred for transcatheter aortic valve replacement (TAVR) underwent ATTR screening by blinded 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) before intervention. ATTR was diagnosed by DPD and absence of monoclonal protein. Reverse remodeling was assessed by comprehensive evaluation before TAVR and at 1 year. RESULTS: One hundred twenty patients (81.8±6.3 years, 51.7% male, 95 lone AS, 25 AS-ATTR) with complete follow-up were studied. At 12 months (interquartile range, 7-17) after TAVR, both groups experienced significant symptomatic improvement by New York Heart Association functional class (both P<0.001). Yet, AS-ATTR remained more symptomatic (New York Heart Association ≥III: 36.0% versus 13.8; P=0.01) with higher residual NT-proBNP (N-terminal pro-brain natriuretic peptide) levels (P<0.001). Remodeling by echocardiography showed left ventricular mass regression only for lone AS (P=0.002) but not AS-ATTR (P=0.5). Global longitudinal strains improved similarly in both groups. Conversely, improvement of regional longitudinal strain showed a base-to-apex gradient in AS-ATTR, whereas all but apical segments improved in lone AS. This led to the development of an apical sparing pattern in AS-ATTR only after TAVR. CONCLUSIONS: Patterns of reverse remodeling differ from lone AS to AS-ATTR, with both groups experiencing symptomatic improvement by TAVR. After AS treatment, AS-ATTR transfers into a lone ATTR cardiomyopathy phenotype.

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.

Relationship of diabetes, heart failure, and N-terminal pro-B-type natriuretic peptide with cardiovascular outcomes in patients with atrial fibrillation.

AIMS: We aim to explore the relationship of heart failure (HF) and diabetes with cardiovascular (CV) death or hospitalization for HF (HHF) and to study the clinical utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an unselected patient population with atrial fibrillation (AF). METHODS AND RESULTS: Patients with AF admitted to a tertiary academic center between January 2005 and July 2019 were identified through a search of electronic health records. We used Cox regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, HF, body mass index, prior myocardial infarction, coronary artery disease, hypertension, smoking, C-reactive protein, and low-density lipoprotein cholesterol. To select the most informative variables, we performed a least absolute shrinkage and selection operator Cox regression with 10-fold cross-validation. In total, 7412 patients (median age 70 years, 39.7% female) were included in this analysis and followed over a median of 4.5 years. Both diabetes [adjusted (Adj.) HR 1.87, 95% CI 1.55-2.25] and HF (Adj. HR 2.57, 95% CI 2.22-2.98) were significantly associated with CV death/HHF after multivariable adjustment. Compared with patients with diabetes, HF patients had a higher risk of HHF but a similar risk of CV and all-cause death. NT-proBNP showed good discriminatory performance (area under the curve 0.78, 95% CI 0.77-0.80) and the addition of NT-proBNP to the covariates used for adjustment resulted in a significant area under the curve improvement (Δ = 0.04, P < 0.001). With least absolute shrinkage and selection operator, the strongest associations for CV death/HHF were obtained for NT-proBNP [HR 1.91 per 1-SD in log-transformed biomarker], HF (HR 1.72), and diabetes (HR 1.56). CONCLUSIONS: Diabetes and HF were independently associated with an increased risk of CV death/HHF in an unselected AF patient population, and NT-proBNP improved risk assessment. These findings suggest that AF patients with diabetes and/or HF should be managed not only for their risk of stroke and systemic embolic events but also for CV death/HHF.

Guideline directed medical therapy and reduction of secondary mitral regurgitation.

BACKGROUND: Guideline-directed medical therapy (GDMT) is the recommended initial treatment for secondary mitral regurgitation (SMR), however, supported by only little comprehensive evidence. This study, therefore, sought to assess the effect of GDMT titration on SMR and to identify specific substance combinations able to reduce SMR severity. METHODS AND RESULTS: We included 261 patients who completed two visits with an echocardiographic exam available within 1 month at each visit. After comprehensively defining GDMT titration as well as SMR reduction, logistic regression analysis was applied in order to assess the effects of overall GDMT titration and specific substance combinations on SMR severity. SMR severity improved by at least 1° in 39.3% of patients with subsequent titration of GDMT and was accompanied by reverse remodelling and clinical improvement. The effects of GDMT titration were significantly associated with SMR reduction (adj. odds ratio 2.91, 95% confidence interval 1.34-6.32, P = 0.007). Moreover, angiotensin receptor/neprilysin inhibitor (ARNi) as well as the combined dosage effects of (i) renin-angiotensin system inhibitors (RASi) and mineralocorticoid-receptor antagonists (MRA), (ii) beta-blockers (BB) and MRA, as well as (iii) RASi, BB, and MRA were all significantly associated with SMR improvement (P < 0.044 for all). CONCLUSION: The present study provides comprehensive evidence for the effectiveness of contemporary GDMT to specifically improve SMR. Our data indicate that GDMT titration conveys a three-fold increased chance of reducing SMR severity. Moreover, the dosage effects of ARNi, as well as the combination of RASi and MRA, BB and MRA, and all three substances in the aggregate are able to significantly improve SMR.

Cerebral Protection in TAVR-Can We Do Without? A Real-World All-Comer Intention-to-Treat Study-Impact on Stroke Rate, Length of Hospital Stay, and Twelve-Month Mortality.

Background: Stroke associated with transcatheter aortic valve replacement (TAVR) is a potentially devastating complication. Until recently, the Sentinel™ Cerebral Protection System (CPS; Boston Scientific, Marlborough, MA, USA) has been the only commercially available device for mechanical prevention of TAVR-related stroke. However, its effectiveness is still undetermined. Objectives: To explore the impact of Sentinel™ on stroke rate, length of hospital stay (LOS), and twelve-month mortality in a single-center, real-world, all-comers TAVR cohort. Material and Methods: Between January 2019 and August 2020 consecutive patients were assigned to TAVR with or without Sentinel™ in a 1:1 fashion according to the treating operator. We defined as primary endpoint clinically detectable cerebrovascular events within 72 h after TAVR and as secondary endpoints LOS and 12-month mortality. Logistic and linear regression analyses were used to assess associations of Sentinel™ use with endpoints. Results: Of 411 patients (80 ± 7 y/o, 47.4% female, EuroSCORE II 6.3 ± 5.9%), Sentinel™ was used in 213 (51.8%), with both filters correctly deployed in 189 (46.0%). Twenty (4.9%) cerebrovascular events were recorded, ten (2.4%) of which were disabling strokes. Patients with Sentinel™ suffered 71% less (univariate analysis; OR 0.29, 95%CI 0.11-0.82; p = 0.02) and, respectively, 76% less (multivariate analysis; OR 0.24, 95%CI 0.08-0.76; p = 0.02) cerebrovascular events compared to patients without Sentinel™. Sentinel™ use was also significantly associated with shorter LOS (Regression coefficient -2.47, 95%CI -4.08, -0.87; p < 0.01) and lower 12-month all-cause mortality (OR 0.45; 95%CI 0.22-0.93; p = 0.03). Conclusion: In the present prospective all-comers TAVR cohort, patients with Sentinel™ use showed (1) lower rates of cerebrovascular events, (2) shortened LOS, and (3) improved 12-month survival. These data promote the use of a CPS when implanting TAVR valves.

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.

The prognostic impact of left ventricular thrombus resolution after acute coronary syndrome and risk modulation via antithrombotic treatment strategies.

BACKGROUND: Left ventricular thrombus (LVT) is a rare but dreaded complication during the acute phase of acute coronary syndrome (ACS). However, profound data on long-term outcome and associated antithrombotic treatment strategies of this highly vulnerable patient population are scarce in current literature. METHODS: Patients presenting with ACS were screened for presence of LVT and subsequently included within a prospective clinical registry. All-cause mortality and the composite of major adverse cardiac events (MACE) and thromboembolic events were defined as primary and secondary endpoint. RESULTS: Within 43 patients presenting with LVT, thrombus resolution during patient follow-up was observed in 27 individuals (62.8%). Patients that reached a resolution of LVT experienced lower incidence rates of death (-23.9%; p = .022), MACE (-37.8%; p = .005), and thromboembolic events (-35.2%; p = .008). Even after adjustment for clinical variables, thrombus resolution showed an independent inverse association with all-cause death with a hazard ratio (HR) of 0.14 (95% CI: 0.03-0.75; p = .021) and as well with MACE with a HR of 0.22 (95% CI: 0.07-0.68; p = .008) and thromboembolic events with a HR of 0.22 (95% CI: 0.06-0.75; p = .015). Triple antithrombotic therapy (TAT) with ticagrelor/prasugrel showed a strong and independent association with thrombus resolution with an adjusted HR of 3.25 (95% CI: 1.22-8.68; p = .019) compared to other strategies. CONCLUSION: The presented data indicate a poor outcome of ACS patients experiencing LVT. In terms of a personalized risk stratification, thrombus resolution has a strong protective impact on both all-cause death and MACE with the potential to tailor treatment decisions-including an intensified antithrombotic treatment approach-in this patient population.

Heart failure with preserved ejection fraction after left-sided valve surgery: prevalent and relevant.

AIMS: To investigate the epidemiological and prognostic relationship between heart failure with preserved ejection fraction (HFpEF) and left-sided valve surgery using all-cause mortality as a primary endpoint. METHODS AND RESULTS: We studied a total of 973 patients, of whom 673 had undergone left-sided valve surgery (time from surgery to enrolment 50 ± 30 months after valve surgery) and 300 patients with HFpEF without prior surgery served as control group. Among patients after surgery, 67.4% fulfilled all criteria of HFpEF according to current guideline recommendations, 20.6% had no heart failure (HF), and 12.0% had HF with mid-range or reduced ejection fraction (HFmrEF/HFrEF). During 83 ± 39 months of follow-up, a total of 335 (34.4%) patients died. Compared to surgical patients with no subsequent HF, patients with HFpEF and HFmrEF/HFrEF after surgery showed significantly higher all-cause mortality rates [hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.25-2.57, P = 0.001; and HR 1.86, 95% CI 1.16-2.98, P = 0.010, respectively]. This increased mortality rate was similar to the control HFpEF group without surgery (HR 2.05, 95% CI 1.38-3.02, P < 0.001). Results remained consistent after adjustment for clinical and imaging risk factors and when using the established HFA-PEFF risk score for HFpEF diagnosis. Notably, only 12.5% of HFpEF patients after surgery were diagnosed with HF despite regular follow-up visits by board-certified cardiologists. In contrast, 92.1% of HFmrEF/HFrEF patients after surgery were diagnosed correctly. CONCLUSIONS: Heart failure with preserved ejection fraction following left-sided valve surgery is highly prevalent, associated with unfavourable outcomes, but rarely recognized.

Clinical Impact of Pre-Procedural Percutaneous Coronary Intervention in Low- and Intermediate-Risk Transcatheter Aortic Valve Replacement Recipients.

The clinical relevance of as well as the optimal treatment strategy for coronary artery disease (CAD) in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) are unclear. Current data are conflicting, and mainly derived from high-risk patients. We aimed to investigate the feasibility and safety of complete revascularization prior to TAVR for severe AS in low- and intermediate-risk patients. We enrolled 449 patients at low (STS score < 4%) and intermediate risk (STS score 4-8%) undergoing TAVR for severe AS and investigated the influence of recent (<3 months) and prior (>3 months) complete revascularization on clinical outcome. Primary study endpoint was all-cause mortality. Overall, 58% of patients had no or non-significant CAD; 18% had a history of complete revascularization prior to TAVR and 24% had complete revascularization shortly before TAVR. Two-year all-cause mortality was not different between patients with recent revascularization prior to TAVR and patients with no or non-significant CAD (13.7% vs. 14.2%, p = 0.905). Cox regression did not reveal an effect on all-cause mortality for recent revascularization. The present analysis reassures that percutaneous complete revascularization prior to TAVR procedures is neutral in terms of all-cause mortality in patients at low and intermediate surgical risk.

Principal Morphomic and Functional Components of Secondary Mitral Regurgitation.

OBJECTIVES: The aim of this work was to identify the key morphological and functional features in secondary mitral regurgitation (sMR) and their prognostic impact on outcome. BACKGROUND: Secondary sMR in patients with heart failure and reduced ejection fraction typically results from distortion of the underlying cardiac architecture. The morphological components which may account for the clinical impact of sMR have not been systematically assessed or correlated with clinical outcomes. METHODS: Morphomic and functional network profiling were performed on a cohort of patients with stable heart failure optimized on guideline-based medical therapy. Principal component (PC) analysis and subsequent cluster analysis were used to condense the morphomic and functional data first into PCs with varimax rotation (PCVmax) and second into homogeneous clusters. Clusters and PCs were tested for their correlations with clinical outcomes. RESULTS: Morphomic and functional data from 383 patients were profiled and subsequently condensed into PCs. PCVmax 1 describes high loadings of left atrial morphological information, and PCVmax 2 describes high loadings of left ventricular (LV) topology. Based on these components, 4 homogeneous clusters were derived. sMR was most prominent in clusters 3 and 4, with the morphological difference being left ventricular size (median end-diastolic volume 188 mL [interquartile range: 160 mL-224 mL] vs 315 mL [264 mL-408 mL]; P < 0.001). Clusters were associated with mortality (P < 0.001), but sMR remained independently associated with mortality after adjusting for the clusters (adjusted HR: 1.42; 95% CI: 1.14-1.77; P < 0.01). The detrimental association of sMR with mortality was mainly driven by cluster 3 (HR: 2.18; 95% CI: 1.32-3.60; P = 0.002), the "small LV cavity" phenotype. CONCLUSIONS: These results challenge the current perceptions that sMR in heart failure with reduced ejection fraction results exclusively from global or local LV remodeling and are suggestive of a potential role of the left atrial component. The association of sMR with mortality cannot be purely attributed to cardiac morphology alone, supporting other complementary key aspects of mitral valve closure consistent with the force balance theory. Unsupervised clustering supports the association of sMR with mortality predominantly driven by the small LV cavity phenotype, as previously suggested by a conceptional framework and termed disproportionate sMR.