Ten-year Durability, Hemodynamic Performance, and Clinical Outcomes after Transcatheter Aortic Valve Implantation Using a Self-expanding Device.

INTRODUCTION: The expansion of transcatheter aortic valve implantation (TAVI) to low-risk and younger patients has increased the relevance of the long-term durability of transcatheter heart valves (THV). The present study aims to assess the 10-year durability, hemodynamic performance, and clinical outcomes after TAVI using the CoreValve system. METHODS: An analysis from a prospective registry with predefined clinical and echocardiographic follow-up included 302 patients who underwent TAVI with the CoreValve system between 2007 and 2015. Bioprosthetic valve failure (BVF) was defined as any bioprosthetic valve dysfunction-related death, re-intervention, or severe hemodynamic valve deterioration. RESULTS: At the time of TAVI, the mean age was 80.41 ± 7.01 years, and the Society of Thoracic Surgeons (STS) score was 6.13 ± 5.23%. At latest follow-up (median [IQR]: 5 [2-7] years), cumulative all-cause mortality rates at 3, 5, 7, and 10 years was 23.7%, 40%, 65.8%, and 89.8%, respectively. Mean aortic valve area and transvalvular gradient post-TAVI and at 5, 7, and 10 years were 1.94, 1.87, 1.69, and 1.98 cm2 (p = 0.236) and 8.3, 9.0, 8.2, and 10.1 mmHg (p = 0.796), respectively. Overall, 11 patients had BVF, of whom six had structural valve deterioration (SVD). The 10-year actual and actuarial freedom from BVF was 96.1% and 78.8%, and from SVD was 97.9% and 80.9%, respectively. Three patients developed significant non-SVD due to severe paravalvular leakage, and two patients were diagnosed with infective endocarditis. CONCLUSION: Using an early-generation self-expanding bioprosthesis, we documented durable hemodynamic performance and low rates of BVF and SVD up to 10 years after TAVI.

Prognostic Value of HFA-PEFF Score in Patients Undergoing Transcatheter Aortic Valve Implantation.

Background The HFA-PEFF score may help in predicting long-term outcomes in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis and preserved left ventricular ejection fraction (EF). Methods We retrieved data from 1,332 patients undergoing TAVI between 2010 and 2019 from the Prospective Segeberg TAVI Registry (ClinicalTrials.gov Identifier: NCT03192774). We calculated the HFA-PEFF score for 1,022 patients who had preserved EF (≥50%). To assess the prognostic value of the HFA-PEFF score in predicting adverse events, we dichotomised the patients according to a cut-off score of five (score <5 group: n=528 (51.6%), score ≥5 group: n=494 (48.3%)). Results The HFA-PEFF score ≥5 groups were older (81.9±6.3 years vs. 80.3±6.9 years; p<0.001) and had a higher prevalence of atrial fibrillation (35.1% vs 20.8%; p<0.001) and chronic kidney disease (30.1% vs 26.1%; p<0.001). Kaplan-Meier survival analyses over 24 months showed increased cardiovascular (CV) mortality (12.5% vs. 7.7%, log-rank; p=0.028) and first heart failure-related rehospitalisation (7.7% vs. 4.0%, log-rank p=0.014) in the HFA-PEFF score ≥5 groups compared with those of lower scores. No significant difference in all-cause mortality between both groups was observed (22.0% vs. 17.9%, log-rank p=0.127). In multivariate analysis, HFA-PEFF score ≥5 failed to predict CV mortality (aHR 1.37, 95% CI: 0.90-2.08, p=0.140) and time to first heart failure-related rehospitalisation (aHR 1.49, 95% CI: 0.83-2.65, p=0.181). Conclusion The HFA-PEFF score showed limited value in predicting long-term mortality and adverse heart failure-related events in patients with preserved EF undergoing TAVI. Clinical variables specific to this population could complement the HFA-PEFF score for better risk prediction.

Feasibility of Coronary Access in Patients With Acute Coronary Syndrome and Previous TAVR.

OBJECTIVES: The aim of this study was to characterize the feasibility of coronary angiography (CA) and percutaneous coronary intervention (PCI) in acute settings among patients who have undergone transcatheter aortic valve replacement (TAVR). BACKGROUND: Impaired coronary access after TAVR may be challenging and particularly in acute settings could have deleterious consequences. METHODS: In this international registry, data from patients with prior TAVR requiring urgent or emergent CA were retrospectively collected. A total of 449 patients from 25 sites with acute coronary syndromes (89.1%) and other acute cardiovascular situations (10.9%) were included. RESULTS: Success rates were high for CA of the right coronary artery (98.3%) and left coronary artery (99.3%) and were higher among patients with short stent-frame prostheses (SFPs) than in those with long SFPs for CA of the right coronary artery (99.6% vs 95.9%; P = 0.005) but not for CA of the left coronary artery (99.7% vs 98.7%; P = 0.24). PCI of native coronary arteries was successful in 91.4% of cases and independent of valve type (short SFP 90.4% vs long SFP 93.4%; P = 0.44). Guide engagement failed in 6 patients, of whom 3 underwent emergent coronary artery bypass grafting and another 3 died in the hospital. Among patients requiring revascularization of native vessels, independent predictors of 30-day all-cause mortality were prior diabetes, cardiogenic shock, and failed PCI but not valve type or success of coronary engagement. CONCLUSIONS: CA or PCI after TAVR in acute settings is usually successful, but selective coronary engagement may be more challenging in the presence of long SFPs. Among patients requiring PCI, prior diabetes, cardiogenic shock, and failed PCI were predictors of early mortality.

5-Year Outcomes After TAVR With Balloon-Expandable Versus Self-Expanding Valves: Results From the CHOICE Randomized Clinical Trial.

OBJECTIVES: The purpose of this study was to evaluate clinical and echocardiographic outcome data of the CHOICE (Randomized Comparison of Transcatheter Heart Valves in High Risk Patients with Severe Aortic Stenosis: Medtronic CoreValve Versus Edwards SAPIEN XT) trial at 5 years. BACKGROUND: The CHOICE trial was designed to compare device performance of a balloon-expandable (BE) transcatheter heart valve (THV) versus a self-expanding (SE) THV. METHODS: The CHOICE trial is an investigator-initiated trial that randomized 241 high-risk patients with severe symptomatic aortic stenosis and an anatomy suitable for treatment with both BE and SE THVs to transfemoral transcatheter aortic valve replacement with either device. The primary endpoint was device success. Patients were followed up to 5 years, with assessment of clinical outcomes, and echocardiographic evaluation of valve function and THV durability. RESULTS: After 5 years, there were no statistically significant differences between BE and SE valves in the cumulative incidence of death from any cause (53.4% vs. 47.6%; p = 0.38), death from cardiovascular causes (31.6% vs. 21.5%; p = 0.12), all strokes (17.5% vs. 16.5%; p = 0.73), and repeat hospitalization for heart failure (28.9% vs. 22.5%; p = 0.75). SE patients had larger prosthetic valve area (1.6 ± 0.5 cm2 vs. 1.9 ± 0.5 cm2; p = 0.02) with a lower mean transprosthetic gradient (12.2 ± 8.7 mm Hg vs. 6.9 ± 2.7 mm Hg; p = 0.001) at 5 years. No differences were observed in the rates of paravalvular regurgitation. Clinical valve thrombosis occurred in 7 BE patients (7.3%) and 1 SE patient (0.8%; p = 0.06), and moderate or severe structural valve deterioration in 6 BE patients (6.6%) and no SE patient (0%; p = 0.018). The rate of bioprosthetic valve failure was low and not significantly different between both groups (4.1% vs. 3.4%; p = 0.63). CONCLUSIONS: Five-year follow-up of patients in the CHOICE trial revealed clinical outcomes after transfemoral transcatheter aortic valve replacement with early-generation BE and SE valves that were not statistically significantly different, with limited statistical power. Forward flow hemodynamics were significantly better with the SE valve. Moderate or severe structural valve deterioration was uncommon but occurred more frequently with the BE valve. (A Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: The CHOICE Trial [CHOICE]; NCT01645202).

Impact of prosthesis-iteration evolution and sizing practice on the incidence of prosthesis-patient mismatch after transcatheter aortic valve replacement.

OBJECTIVES: To investigate the impact of the introduction of the next generation self-expanding (SE) and balloon-expandable (BE) transcatheter heart valves (THVs) on the incidence of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR). BACKGROUND: PPM is a risk factor for accelerated degeneration of bioprosthetic aortic valves. Data on PPM after TAVR are derived mainly from studies of older generation THVs. METHODS: PPM was assessed at 30 days post-TAVR with the older generation (Medtronic CoreValve, n = 120 and Edwards Sapien XT, n = 121) and the next generation THVs (Medtronic Evolut R/Pro, n = 136 and Edwards Sapien 3, n = 363). RESULTS: The incidence of any and severe PPM was 15.1% and 0.0% for the older generation THVs, and 42.8% and 12.1% for the next generation THVs. The incidence of moderate and severe PPM was 23.3% and 3.5% in patients who received an Evolut R/Pro vs. 33.1% and 14.7% in those who received a Sapien 3 (P < 0.001). On multivariable analysis, TAVR with the Sapien 3 THV was not associated with PPM, while left ventricular ejection fraction (0.97 [0.95-0.99], P = 0.002), history of myocardial infarction (2.09 [1.00-4.34], P = 0.049), annulus maximum diameter (0.84 [0.77-0.92], P < 0.001), and THV oversizing (0.90 [0.87-0.94], P < 0.001) were independently associated with PPM. In Sapien 3, the risk of any and severe PPM was higher in those with no oversizing (odds ratio: 3.25 [1.23-8.53], P = 0.017 and 5.79[2.33-14.36], P < 0.001). CONCLUSIONS: The incidence of PPM in contemporary TAVR is significant, especially with the next generation BE THV without adequate oversizing.

Clinical Valve Thrombosis After Transcatheter Aortic Valve-in-Valve Implantation.

Background Limited data exist on clinical valve thrombosis after transcatheter aortic valve-in-valve (ViV) implantation. Our objective was to determine the incidence, timing, clinical characteristics, and treatment outcomes of patients diagnosed with clinical ViV thrombosis. Methods and Results Centers participating in the Valve-in-Valve International Data Registry were surveyed for thrombosis cases, and clinical valve thrombosis was defined based on a combination of the presence of new valve dysfunction and an imaging evidence of leaflet thrombosis. Three hundred ViV implantations were included. The surgical valve was stented in 86.3% and stentless in 13.7% of cases; and the transcatheter heart valve was self-expanding in 50%, balloon-expandable in 49%, and mechanically expanding in 1.0%. The incidence of clinical valve thrombosis was 7.6% (n=23), diagnosed at a median time of 101 days (interquartile range, 21-226) after the procedure. Fifteen patients (65%) presented with worsening symptoms and 21 (91%) with transvalvular mean gradient elevation. The mean gradient at the time of diagnosis (median 39 mm Hg; interquartile range, 30-44) was significantly higher than immediately post-ViV (13 mm Hg; interquartile range, 8-20.5; P<0.001) and was significantly reduced after oral anticoagulation therapy (17.5 mm Hg; interquartile range, 11-20.5; P<0.001). There were no deaths or strokes related to valve thrombosis. Factors associated with valve thrombosis were oral anticoagulation (odds ratio [95% confidence limits]: 0.067 [0.008-0.543], P=0.011), surgical valve true internal diameter indexed to body surface area (0.537 [0.331-0.873], P=0.012), and Mosaic or Hancock II stented porcine bioprostheses (4.01 [1.287-12.485], P=0.017). Conclusions Clinical valve thrombosis after transcatheter aortic ViV implantation is common, especially in patients not on oral anticoagulation. Although aortic ViV is commonly associated with elevated gradients, valve thrombosis should be ruled out if gradients increase compared with early postprocedural values. A higher incidence was observed after treatment of certain stented porcine surgical valve types, suggesting a specific adjustment of the adjunctive antithrombotic therapy in this subset of ViV patients.

Bioprosthetic Valve Performance After Transcatheter Aortic Valve Replacement With Self-Expanding Versus Balloon-Expandable Valves in Large Versus Small Aortic Valve Annuli: Insights From the CHOICE Trial and the CHOICE-Extend Registry.

OBJECTIVES: The aim of this study was to compare self-expanding and balloon-expandable transcatheter heart valves (THVs) in large versus small aortic valve annuli. BACKGROUND: The degree of THV oversizing varies according to annular size, and this can modify the hemodynamic performance of self-expanding and balloon-expandable THVs. METHODS: Patients undergoing transcatheter aortic valve replacement in the randomized CHOICE (Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: Medtronic CoreValve vs Edwards SAPIEN XT) trial (CoreValve [CV], n = 120; SAPIEN XT [SXT], n = 121) and the nonrandomized CHOICE-Extend registry (Evolut R [ER], n = 100; SAPIEN 3 [S3], n = 334) were compared for THV performance by echocardiography (in all patients) and by cardiac magnetic resonance imaging (MRI) regurgitant fraction (RF) (in a subgroup of patients). Patients were stratified according to aortic valve annular mean diameter into those with large (>23 mm) or small (≤23 mm) annuli. RESULTS: THV percentage oversizing was 19.1 ± 6.4% with the CV, 11.4 ± 7.0% with the SXT, 18.8 ± 4.8% with the ER, and 3.7 ± 5.5% with the S3. Transvalvular mean pressure gradient was lower with the CV and ER than with the SXT and S3 in both the large and small annulus groups. In the randomized CHOICE trial, moderate to severe prosthetic valve regurgitation (PVR) was more with the CV than the SXT in large annuli (15.1% vs. 0.0%; p = 0.002; MRI RF: 10.5 ± 10.2% vs. 4.4 ± 4.5%; p = 0.036) but not in small annuli (0.0% vs. 5.7%; p = 0.50; MRI RF: 4.0 ± 4.1% vs. 4.0 ± 3.4%; p = 0.98). In the CHOICE-Extend registry, moderate to severe PVR occurred in 2 patients, and any PVR was not significantly different between the ER and the S3 in large (41.7% vs. 32.5%; p = 0.24) or small (47.1% vs. 43.8%; p = 0.84) annuli. MRI RF was not different in large annuli (5.0 ± 3.8% vs. 5.0 ± 6.1%; p = 0.99) but was significantly lower with the ER than the S3 in small annuli (2.9 ± 2.3% vs. 4.8 ± 3.7%; p = 0.023). On multivariate analysis, transcatheter aortic valve replacement with the ER in small annuli was associated with a lower rate of prosthesis-patient mismatch than with the S3, with no increased risk for PVR. CONCLUSIONS: Older-generation balloon-expandable THVs were associated with less PVR than self-expanding THVs in patients with large but not small annuli. The next-generation self-expanding THV has improved sealing in patients with large annuli and may have potential advantages in patients with small annuli.

Nitrated fatty acids suppress angiotensin II-mediated fibrotic remodelling and atrial fibrillation.

AIM: Atrial fibrosis, one of the most striking features in the pathology of atrial fibrillation (AF), is promoted by local and systemic inflammation. Electrophilic fatty acid nitroalkenes, endogenously generated by both metabolic and inflammatory reactions, are anti-inflammatory mediators that in synthetic form may be useful as drug candidates. Herein we investigate whether an exemplary nitro-fatty acid can limit atrial fibrosis and AF. METHODS AND RESULTS: Wild-type C57BL6/J mice were treated for 2 weeks with angiotensin II (AngII) and vehicle or nitro-oleic acid (10-nitro-octadec-9-enoic acid, OA-NO2, 6 mg/kg body weight) via subcutaneous osmotic minipumps. OA-NO2 significantly inhibited atrial fibrosis and depressed vulnerability for AF during right atrial electrophysiological stimulation to levels observed for AngII-naive animals. Left atrial epicardial mapping studies demonstrated preservation of conduction homogeneity by OA-NO2. The protection from fibrotic remodelling was mediated by suppression of Smad2-dependent myofibroblast transdifferentiation and inhibition of Nox2-dependent atrial superoxide formation. CONCLUSION: OA-NO2 potently inhibits atrial fibrosis and subsequent AF. Nitro-fatty acids and possibly other lipid electrophiles thus emerge as potential therapeutic agents for AF, either by increasing endogenous levels through dietary modulation or by administration as synthetic drugs.