Ex vivo evaluation of 3 different right ventricular outflow tract substitutes.

OBJECTIVES: The Ross procedure represents an excellent treatment option in younger patients with aortic stenosis but is limited by poor availability of homografts. In this study, we investigated the hydrodynamic performance of 3 different types of right ventricular outflow tract replacement with pericardium or synthetic material. METHODS: Three different types of valved conduits were constructed using pericardium and/or synthetic material (Group PEPE: pericardial cusps and pericardial conduit, Group PEPR: pericardial cusps and Dacron conduit, Group PRPR: expanded polytetrafluoroethylene cusps and Dacron conduit). The conduits were designed according to the Ozaki method. Their hydrodynamic performance (effective orifice area, mean pressure gradient and leakage volume) were evaluated in a mock circulation loop at different hydrodynamic conditions. RESULTS: Hydrodynamic assessment showed significantly larger effective orifice area of PEPE and PEPR compared to PRPR under all conditions and there were no significant differences between PEPE and PEPR [for condition 2: PEPE 2.43 (2.35-2.54) cm2, PEPR: 2.42 (2.4-2.5) cm2, PRPR: 2.08 (1.97-2.21) cm2, adjusted pairwise comparisons: PEPE versus PEPR: P = 0.80, PEPE versus PRPR: P < 0.001, PEPR versus PRPR: P < 0.001]. Mean pressure gradient was significantly lower for PEPE and PEPR compared with PRPR, whereas no significant differences were seen between PEPE and PEPR. Leakage volume was significantly lower for PEPE and PEPR compared with PRPR under all conditions while leakage was similar between PEPE and PEPR. CONCLUSIONS: Pulmonary graft reconstruction with pericardium cusps showed superior hydrodynamic performance compared with polytetrafluoroethylene cusps. Our results suggest that it could be considered as an alternative substitute for right ventricular outflow tract replacement during the Ross procedure.

Association of pulmonary hypertension with the outcome in patients undergoing edge-to-edge mitral valve repair.

OBJECTIVES: The association of pulmonary hypertension (PH) with the outcome after mitral transcatheter edge-to-edge repair (M-TEER) focusing on the new ESC/ERS guidelines definition for PH. BACKGROUND: PH is frequently found in patients with mitral regurgitation and is associated with lower survival rates. Recent studies were based on echocardiographic parameters, but results based on invasive haemodynamics differentiating distinct types of PH using the new definition for PH are missing. METHODS: 449 consecutive M-TEER-treated patients from December 2009 to February 2015 were included in this retrospective analysis. All patients were stratified by the distinct types of PH (no PH, precapillary PH, isolated postcapillary PH, combined post-PH and precapillary PH) according to the definitions of the ESC/ERS guidelines for the diagnosis of PH from 2015 (meanPA cut-off <25 mm Hg, pulmonary capillary wedge pressure (PCWP) cut-off ≤15 mm Hg, diastolic pulmonary gradient cut-off ≥7 mm Hg or pulmonary vascular resistance (PVR) >3 WU) and 2022 (meanPA cut-off ≤20 mm Hg, PCWP cut-off ≤15 mm Hg, PVR cut-off ≥3 WU). RESULTS: Patients with any type of PH (2015: meanPA cut-off 25 mm Hg; 2022: meanPA cut-off >20 mm Hg) showed a higher risk of death after M-TEER compared with patients with no PH (2015: HR 1.61 (95% CI 1.25 to 2.07); p<0.001 and 2022: HR 2.09 (95% CI 1.54 to 2.83); p<0.001). Based on the new PH definition, each PH subgroup showed a lower survival after M-TEER compared with patients with no PH. Echocardiographic estimated systolic PAP showed a correlation with invasively measured mean pulmonary artery pressure (mPAP) (r=0.29, p<0.001) and systolic pulmonary arterial pressure (r=0.34,p<0.001). Cox-regression analysis showed higher invasive diastolic, systolic and mean pulmonary pressures were associated with higher all-cause mortality (p<0.001). In addition, invasive measured higher right atrial pressure, lower pulmonary arterial compliance, higher PVR and higher wedge pressure were identified as predictors of all-cause mortality after M-TEER. CONCLUSIONS: The new PH definition discriminates PH groups and mortality better than the old definition. The lower threshold of mPAP of 20mmHg improved prognostication in this cohort of patients.

Impact of heart rate, aortic compliance and stroke volume on the aortic regurgitation fraction studied in an ex vivo pig model.

INTRODUCTION: Drug therapy to reduce the regurgitation fraction (RF) of high-grade aortic regurgitation (AR) by increasing heart rate (HR) is generally recommended. However, chronic HR reduction in HFREF patients can significantly improve aortic compliance and thereby potentially decrease RF. To clarify these contrasts, we examined the influence of HR, aortic compliance and stroke volume (SV) on RF in an ex vivo porcine model of severe AR. METHODS: Experiments were performed on porcine ascending aorta with aortic valves (n=12). Compliance was varied by inserting a Dacron graft close to the aortic valve. Both tube systems were connected to a left heart simulator varying HR and SV. AR was accomplished by punching a 0.3 cm2 hole in one aortic cusp. Flow, RF, SV and aortic pressure were measured, aortic compliance with transoesophageal ultrasound probes. RESULTS: Compliance of the aorta was significantly reduced after Dacron graft insertion (0.55%±0.21%/mm Hg vs 0.01%±0.007%/mm Hg, p<0.001, respectively). With increasing HR, RF was significantly reduced in each steady state of the native aorta (HR 40 bpm: 88%±7% vs HR 120 bpm: 42%±10%; p<0.001), but Dacron tube did not affect RF (HR 40 bpm: 87%±8%; p=0.79; HR 120 bpm: 42%±3%; p=0.86). Increasing SV also reduced RF independent of the stiff Dacron graft. CONCLUSION: Aortic compliance did not affect AR in the ex vivo porcine model of AR. RF was significantly reduced with increasing HR and SV. These results affirm that HR lowering and negative inotropic drugs should be avoided to treat severe AR.

Elucidation of the genetic causes of bicuspid aortic valve disease.

AIMS: The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect. METHODS AND RESULTS: We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 × 10-08) and was replicated in an independent case-control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 × 10-16), GATA4 (P = 1.61 × 10-09), and TEX41 (P = 7.68 × 10-04). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and ∼20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology. CONCLUSION: Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.

A Novel Model to Predict 1-Year Mortality in Elective Transfemoral Aortic Valve Replacement: The TAVR-Risk Score.

OBJECTIVES: We aimed to develop and validate an effective prediction model for 1-year mortality risk in elective transfemoral transcatheter aortic valve replacement (TAVR), ie, the TAVR-Risk (TARI) model. BACKGROUND: TAVR is the primary treatment for patients with symptomatic severe aortic valve stenosis; however, risk assessment tools for longer-term outcomes after TAVR remain scarce. METHODS: This retrospective cohort study used logistic regression to test univariate and multivariate associations. The German Aortic Valve Registry (GARY) was the derivation (n = 20,704) and the Swedish SWEDEHEART TAVR Registry (SWENTRY) was the validation cohort (n = 3982). The main outcome was the area under the curve (AUC) in the prediction of 1-year mortality. The final model included 12 parameters that were associated with 1-year mortality in a multivariate analysis. RESULTS: The TARI model (AUC, 0.66; 95% confidence interval [CI] 0.65-0.67) performed better as compared with the Society of Thoracic Surgeons (STS) score (AUC, 0.63; 95% CI, 0.62-0.64; P<.001) and logistic EuroSCORE I (AUC, 0.60; 95% CI, 0.59-0.61; P<.001) in the GARY derivation cohort, and discriminated the risk for 1-year mortality better than logistic EuroSCORE I in the SWENTRY validation cohort (AUC, 0.62; 95% CI, 0.60-0.64 vs AUC, 0.59; 95% CI, 0.57-0.61; P=.04). CONCLUSIONS: This novel TARI score provides a relatively easy-to-use risk model and offers a superior prediction for 1-year mortality in European TAVR patients.

Impact of high-pressure balloon aortic valvuloplasty on the hydrodynamic result after a transcatheter valve-in-valve procedure.

OBJECTIVES: The aim of this study was to investigate the degree of functional improvement of a transcatheter heart valve (THV) for valve-in-valve after bioprosthetic valve fracture (BVF) of three small surgical aortic valve bioprostheses (SAVBP) using high-pressure balloon aortic valvuloplasty (HP-BAV) under standardized ex-vivo-conditions. METHODS: A THV 26 mm (Evolut R) and SAVBP 21 mm (Perimount Magna Ease, Trifecta, and Epic supra [n = 4] were used. Mean pressure gradient (MPG), effective orifice area (EOA), geometric orifice area (GOA), minimal internal diameter (MID), and pinwheeling index (PWI) were analyzed before and after HP-BAV of the SAVBP using a noncompliant balloon. Fracturing of the SAVBP was done before implantation of the THV and the balloon pressures at the point of fracture were recorded. RESULTS: The Magna Ease and Epic fractured at balloon pressures of 18 and 8 atm, respectively. The Trifecta did not fracture up to a balloon pressure of 30 atm but was dilated. HP-BAV led to increased THV expansion as evident by straightened coaptation lines of the Evolut R 26 mm with reduced PWI, increased MID, and increased GOA in all 21 mm SAVBP. Evolut R showed significantly lower MPG and higher EOA as ViV in all prostheses after HP-BAV (p < 0.001). MPG and EOA of Evolut R differed regarding the SAVBP. Evolut R presented the lowest MPG and highest EOA in Magna Ease and the highest MPG and lowest EOA in Epic supra. CONCLUSIONS: The degree of function improvement of the same THV as ViV after HP-BAV depends on the surgical valve model. Functional improvement can also be achieved without valve fracture.

Functional performance of 8 small surgical aortic valve bioprostheses: an in vitro study.

OBJECTIVES: Selection of a surgical aortic valve (SAV) bioprosthesis model for the treatment of aortic valve disease remains controversial. The aim of this study was to characterize the functional performance of 8 SAV models in a standardized in vitro setting. METHODS: The hydrodynamic performance of 8 SAVs with labelled size 21 mm (Avalus™, Hancock® II, Mosaic® Ultra™, Perimount®, Perimount® Magna Ease, Epic™ Supra, Trifecta™ GT; Freestyle®), was investigated in a pulse duplicator. Transvalvular pressure gradients and effective orifice area (EOA) were recorded. The geometrical orifice area and physical dimensions of the valves were determined, and new functional dimensions were introduced. RESULTS: Mean pressure gradient (MPG) and EOA differed significantly between the analysed SAVs. The Epic presented with the lowest EOA and highest MPG, while the Trifecta showed the highest EOA and the lowest MPG. We introduce a useful way to determine the minimal internal diameter and a new measure termed 'relative orifice area' to characterize a valve's performance. CONCLUSIONS: SAVs showed significant differences in their hydrodynamic performance despite the same label size. This finding was related to the construction of the valves. We introduce a new measure that characterizes the functional performance of a valve model and size for the treatment of an aortic annulus of a specific size. Our data emphasize that SAV selection should carefully be done using an individual patient approach and that future research is necessary to improve the current generation of SAVs.

Ex vivo evaluation of the Ozaki procedure in comparison with the native aortic valve and prosthetic valves.

OBJECTIVES: We investigated the hydrodynamic performance and cusp kinematics of the Ozaki neocuspidized aortic valve in comparison with the native aortic and prosthetic valves in an ex vivo study. METHODS: Native aortic valves of swine hearts were replaced by aortic valve substitutes, and their hydrodynamic performance (effective orifice area and mean pressure gradient) was evaluated in a mock circulation under defined conditions. The following aortic valve substitutes were investigated: native aortic valve, Ozaki valve, Perimount Magna Ease, Trifecta and St. Jude Medical Masters. All prosthetic valves had a labelled size of 21 mm. RESULTS: The Ozaki valve and native aortic valve showed a similar and significantly larger orifice area than all investigated prosthetic valves particularly at high flow rates. There was no significant difference between the Ozaki valve and the native aortic valve. The native aortic valve and Ozaki valve showed a similar increase in orifice area with increasing flow through the valve while prosthetic valves showed a markedly weaker increase. Similarly, the native and Ozaki valve showed a similar increase in mPG with forward flow which was weaker than prosthetic valves. Cusp kinematics were similar between the native and Ozaki valve, whilst prosthetic valves were clearly distinguishable from them. CONCLUSIONS: The Ozaki procedure showed excellent hydrodynamic performance compared to prosthetic valves and showed similar cusp motion characteristics to the native aortic valve. Our results suggest that the Ozaki neocuspidized valve behaves physiologically in many aspects, which may contribute to beneficial clinical outcomes.

Surgical aortic valve replacement in patients aged 50-69 years-insights from the German Aortic Valve Registry (GARY).

OBJECTIVES: The aim of this study was to analyse the outcome of patients between 50 and 69 years of age undergoing biological or mechanical aortic valve replacement. METHODS: Data were collected from the German Aortic Valve Registry. Data were analysed regarding baseline characteristics and outcome parameters such as 5-year survival, stroke and reintervention. RESULTS: In total.3046 patients undergoing isolated surgical aortic valve replacement between 2011 and 2012 were investigated and a propensity score matching was performed. Within this period, 2239 patients received a biological prostheses, while 807 patients received a mechanical prosthesis. Mean age in the biological group was 63.07 (±5.11) and 57.34 (±4.67) in the mechanical group (standardized mean difference 1.172). In the overall cohort, there were more female patients in the biological group (32.7% vs 28.4%) and log EuroSCORE I was higher (5.41% vs 4.26%). After propensity matching (610 pairs), there was no difference in the mortality at 5-year follow-up (12.1% biological vs 9.2% mechanical P = 0.05) nor for reoperation/reintervention (2.5% biological vs 2.0% mechanical, P = 0.546). Patients undergoing mechanical aortic valve replacement suffered from a higher stroke rate 3.3% vs 1.5% (P = 0.04) at 5-year follow-up. CONCLUSIONS: Aortic valve replacement with biological or mechanical prostheses showed similar 5-year outcomes for survival and reoperation in a propensity-matched cohort, but significantly increased stroke rate after mechanical aortic valve replacement. This could influence the choice of a mechanical valve in younger patients.

The figure-of-8 aortic valve suturing technique optimizes the effective orifice area of a small aortic annulus-an ex vivo study.

OBJECTIVES: Surgical aortic valve replacement (SAVR) in small annuli carries an elevated risk for the patient-prosthesis mismatch. In this study, we systematically investigated the influence of different implantation techniques including annular enlargement (AE) on the functional result after SAVR in small annuli using a standardized ex vivo model. METHODS: SAVR using the PERIMOUNT Magna Ease® (PME) 21 mm was performed in small porcine aortic roots using 4 implantation techniques: non-everting pledgeted (NE) suture, single interrupted (SI) suture, continuous suture (CS), figure-of-8 (F8) suture, as well as the PME 23 mm after AE using the Nunez method and the NE suture technique (PME23 AE). The effective orifice area (EOA), mean pressure gradient and leakage volume were evaluated using a mock circulation loop in accordance with ISO regulations. RESULTS: Experiments were conducted on 31 porcine aortic roots. PME21 using F8 and PME23 after AE achieved a significantly larger EOA than using NE. PME23 after AE showed a larger EOA than the PME21 using any suture technique, except the F8 [for stroke volume of 74 ml: PME21 NE: 1.68 (1.63-1.72) cm2, PME21 SI: 1.76 (1.68-1.81) cm2 (P = 0.17), PME21 CS: 1.76 (1.65-1.79) cm2 (P = 0.14), PME21 F8: 1.81 (1.70-1.85) cm2 (P = 0.005); PME23 AE: 1.83 (1.73-1.92) cm2 (P < 0.001)]. SI and CS did not result in larger EOA compared with the NE technique. PME21 using SI had a significantly larger leakage volume than using NE and there was no significant difference between other techniques [for stroke volume of 74 ml: PME21 NE: 3.51 (1.85-4.53) ml/stroke, PME21 SI: 6.00 (4.02-7.06) ml/stroke (P < 0.001), PME21 CS: 4.04 (3.60-4.49) ml/stroke (P = 0.10), PME21 F8: 3.16 (1.99-3.62) ml/stroke (P = 0.74), PME23 NE: 2.89 (2.45-4.72) ml/stroke (P = 0.51)]. CONCLUSIONS: The F8 technique with the PME21 achieved a similar EOA as the 1 size larger PME23 using NE after AE. These results suggest that the F8 technique may be an effective surgical modification to improve the haemodynamic result in a small annulus without additional AE.

Impact of different valve-in-valve positions on the hydrodynamic performance of the newest-generation self-expanding transcatheter heart valve.

OBJECTIVES: Transcatheter aortic valve-in-valve (ViV) procedures are increasingly performed for the treatment of degenerated surgical aortic valves with a high risk for a redo operation. For an optimal functional result, precise positioning of the transcatheter heart valve (THV) inside the SHV is crucial. The aim of this study was to systematically investigate the impact of implantation depth on the functional result after a ViV procedure in a standardized in vitro setting. METHODS: A THV 23 mm (Evolut PRO) and 3 SHV 21 mm (Perimount Magna Ease, Trifecta and Hancock II) were used for hydrodynamic testing with a constant heartbeat 64/min and a range of 55-105 ml of stroke volume in 5 different positions of the THV. The following parameters were analysed: mean pressure gradient (MPG), effective orifice area (EOA), geometric orifice area, minimal internal diameter and pin-wheeling index. RESULTS: MPG and EOA differed significantly regarding the position of the THV in the same SHV. The highest EOA and the lowest MPG were recorded for Evolut PRO with significance for both parameters in Hancock II at 4 vs 5 mm (P < 0.001), in Magna Ease at 2 mm (vs 3 mm and vs 6 mm, P < 0.001) and in Trifecta at 4 mm (vs 5 and 6 mm, P < 0.001). Leaflet coadaptation, minimal internal diameter and maximal geometric orifice area of the same TAV differ regarding the position of the TAV. CONCLUSIONS: The optimal position for hydrodynamic performance of the THV as ViV differs among specific SHV models. The findings may be useful for planning a ViV procedure using the Evolut PRO THV.

Chalcone-Supported Cardiac Mesoderm Induction in Human Pluripotent Stem Cells for Heart Muscle Engineering.

Human pluripotent stem cells (hPSCs) hold great promise for applications in cell therapy and drug screening in the cardiovascular field. Bone morphogenetic protein 4 (BMP4) is key for early cardiac mesoderm induction in hPSC and subsequent cardiomyocyte derivation. Small-molecular BMP4 mimetics may help to standardize cardiomyocyte derivation from hPSCs. Based on observations that chalcones can stimulate BMP4 signaling pathways, we hypothesized their utility in cardiac mesoderm induction. To test this, we set up a two-tiered screening strategy, (1) for directed differentiation of hPSCs with commercially available chalcones (4'-hydroxychalcone [4'HC] and Isoliquiritigen) and 24 newly synthesized chalcone derivatives, and (2) a functional screen to assess the propensity of the obtained cardiomyocytes to self-organize into contractile engineered human myocardium (EHM). We identified 4'HC, 4-fluoro-4'-methoxychalcone, and 4-fluoro-4'-hydroxychalcone as similarly effective in cardiac mesoderm induction, but only 4'HC as an effective replacement for BMP4 in the derivation of contractile EHM-forming cardiomyocytes.

An ex vivo evaluation of two different suture techniques for the Ozaki aortic neocuspidization procedure.

OBJECTIVES: We investigated the Ozaki procedure using a single interrupted suture technique (SST) and compared this with the standard continuous suture technique (CST) with regard to hydrodynamic valve performance. In addition, both techniques were compared with the native aortic valve (NAV). METHODS: Effective orifice area, mean pressure gradient and leakage volume were evaluated in the NAV as well as after an Ozaki procedure using SST or CST in fresh swine aortic roots using a mock circulation loop. The NAV, SST and CST were evaluated under 4 defined hydrodynamic conditions. RESULTS: Both suture techniques resulted in a similar effective orifice area under all conditions [for stroke volume of 70 ml: SST: 1.50 (1.35-1.87) vs CST: 1.57 (1.41-1.72) cm2, P = 0.8] and there were no significant differences between both suture techniques and the NAV (P > 0.05). Regarding mean pressure gradient, the Ozaki procedure with SST and CST showed no significant differences [7.23 (5.53-8.91) vs 7.04 (6.65-7.60) mmHg, P = 0.72] and there was no significant difference between both suture techniques and the NAV (P > 0.1). In leakage volume, there was no significant difference between SST and CST [4.49 (3.91-4.99) vs CST: 4.23 (3.58-4.87) ml/stroke, P = 0.34]. CONCLUSIONS: The Ozaki procedure with SST performed similarly to that with CST with regard to hydrodynamic performance. Our results suggest that the Ozaki procedure can be performed with SST instead of CST, which may be useful in patients with limited surgical exposure, such as a small annulus.

Five-year outcome in 18 010 patients from the German Aortic Valve Registry.

OBJECTIVES: To determine the 5-year outcome in patients treated by isolated transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (sAVR)-a prospective observational cohort study. METHODS: A total of 18 010 patients were included (n = 8942 TAVI and n = 9068 sAVR) in the German Aortic Valve Registry (GARY) who were treated in 2011 and 2012 at 92 sites in central Germany. Eligible patients with TAVI and sAVR were matched using propensity scores in a nearest-neighbour approach. Patients with repeat procedures or unequivocal indication for one treatment option (e.g. frailty) were excluded (n = 4785 for TAVI and n = 2 for sAVR). This led to 13 223 patients (4157 TAVI and 9066 sAVR) as an unmatched subcohort. The main outcome measure was the 5-year all-cause mortality. RESULTS: TAVI patients were significantly older (80.9 ± 6.1 vs 68.5 ± 11.1 years, P < 0.001), had a higher Society of Thoracic Surgeons (STS) score (6.3 ± 4.9 vs 2.6 ± 3.0, P < 0.001) and a higher 5-year all-cause mortality (49.8% vs 16.5%, P < 0.0001). There was no major difference in in-hospital stroke, in-hospital myocardial infarction, or temporary and chronic dialysis. In the propensity score-matched group (n = 3640), there were 763 deaths (41.9%) among 1820 TAVI patients compared with 552 (30.3%) among 1820 treated with sAVR during the 5-year follow-up (hazard ratio 1.51, 95% confidence interval 1.35-1.68; P < 0.0001). New pacemaker implantation was performed in 448 patients (24.6%) after TAVI and in 201 (11.0%) after sAVR (P < 0.0001). CONCLUSIONS: The 5-year follow-up data show that TAVI patients were significantly older and had a higher STS score than sAVR patients. After propensity score matching, TAVI with early-generation prosthesis was associated with significantly higher 5-year all-cause mortality than sAVR.

Long-Term Outcomes of Patients Undergoing the Ross Procedure.

BACKGROUND: Treatment of aortic-valve disease in young patients still poses challenges. The Ross procedure offers several potential advantages that may translate to improved long-term outcomes. OBJECTIVES: This study reports long-term outcomes after the Ross procedure. METHODS: Adult patients who were included in the Ross Registry between 1988 and 2018 were analyzed. Endpoints were overall survival, reintervention, and major adverse events at maximum follow-up. Multivariable regression analyses were performed to identify risk factors for survival and the need of Ross-related reintervention. RESULTS: There were 2,444 adult patients with a mean age of 44.1 ± 11.7 years identified. Early mortality was 1.0%. Estimated survival after 25 years was 75.8% and did not statistically differ from the general population (p = 0.189). The risk for autograft reintervention was 0.69% per patient-year and 0.62% per patient-year for right-ventricular outflow tract (RVOT) reintervention. Larger aortic annulus diameter (hazard ratio [HR]: 1.12/mm; 95% confidence interval [CI]: 1.05 to 1.19/mm; p < 0.001) and pre-operative presence of pure aortic insufficiency (HR: 1.74; 95% CI: 1.13 to 2.68; p = 0.01) were independent predictors for autograft reintervention, whereas the use of a biological valve (HR: 8.09; 95% CI: 5.01 to 13.08; p < 0.001) and patient age (HR: 0.97 per year; 95% CI: 0.96 to 0.99; p = 0.001) were independent predictors for RVOT reintervention. Major bleeding, valve thrombosis, permanent stroke, and endocarditis occurred with an incidence of 0.15% per patient-year, 0.07% per patient-year, 0.13%, and 0.36% per patient-year, respectively. CONCLUSIONS: The Ross procedure provides excellent survival over a follow-up period of up to 25 years. The rates of reintervention, anticoagulation-related morbidity, and endocarditis were very low. This procedure should therefore be considered as a very suitable treatment option in young patients suffering from aortic-valve disease. (Long-Term Follow-up After the Autograft Aortic Valve Procedure [Ross Operation]; NCT00708409).

State-of-the-art: Insights from the Ross Registry.

The treatment of aortic valve disease in young patients is still a major clinical challenge, as the pre-eminent emphasis is on durability and long-term outcomes beyond 10 to 15 years, sometimes >20 to 30 years. The Ross procedure uses the autologous pulmonary valve as an aortic valve substitute and aims to improve valve durability while avoiding anticoagulation and therefore achieve a sustained long-term result with regard to survival, valve functionality, and quality of life. However, this procedure is technically demanding and only performed at a low frequency. Data investigating the Ross procedure are mostly limited to observational studies from single expert centers, while sufficient randomized data are almost completely lacking. Therefore, to create a clinically relevant database of this therapy, the multicenter Ross Registry was founded in 2001. New patients were included, follow-up of past patients continuously updated, and outcomes regularly reported. Throughout recent years, numerous analyses have been performed to characterize this patient population, surgical techniques, risk factors for morbidity and mortality, and most importantly survival outcomes. Currently, more than 2500 patients are included, and the long-term follow-up has reached >25 years in the very first patients who were included. In the most recent study, 2444 adult patients with a mean age of 44.1 ± 11.7 years were analyzed, and it showed that excellent mid-term survival is maintained after 25 years. In addition, the rate of reintervention was lower than reported in patients with xenografts and anticoagulation-related morbidity lower than reported in patients with mechanical valves. In the absence of robust randomized controlled trials, registry data are very important to monitor outcomes and mirror the quality of current practice. Therefore, the Ross Registry provides a unique and important data base regarding treatment of aortic valve disease in young patients.

Transcatheter Versus Rapid-Deployment Aortic Valve Replacement: A Propensity-Matched Analysis From the German Aortic Valve Registry.

OBJECTIVES: This study sought to compare patient characteristics, procedural outcomes, and valve hemodynamics of surgical aortic valve replacement (SAVR) with current-generation rapid-deployment valves (RDVs) versus transcatheter aortic valve replacement (TAVR) with current-generation transcatheter heart valves (THVs). BACKGROUND: The patient population currently treated with RDVs may have potential similarities with the current TAVR population, but comparative studies in a large patient population remain scarce. METHODS: A total of 16,473 patients who underwent isolated SAVR using current-generation RDVs or isolated transfemoral TAVR with current-generation THVs between 2011 and 2017 were enrolled into the German Aortic Valve Registry. Baseline, procedural, and in-hospital outcome parameters were analyzed for RDVs and THVs before and after 1:1 propensity score matching. Furthermore, RDVs and THVs with similar design characteristics were compared with each other. RESULTS: A total of 1,743 patients received SAVR with an RDV, whereas 14,730 patients were treated with transfemoral TAVR. Patients treated with TAVR were significantly older and had higher surgical risk scores. Following valve replacement, patients treated with an RDV had a significantly higher rate of disabling stroke (1.7% vs. 1.1%; p = 0.03), need for transfusion of >4 red blood cell units (8.5% vs. 1.4%; p < 0.001), and new onset renal replacement therapy (1.9% vs. 1.2%; p = 0.01), whereas the need for a new permanent pacemaker was lower (8.4% vs. 14.9%; p < 0.001). In-hospital mortality was similar (1.6% vs. 1.8%; p = 0.62). These findings persisted after 1:1 propensity score matching, but in-hospital mortality was significantly higher after RDVs (1.7% vs. 0.6%; p = 0.003). Balloon-expandable (BE) RDVs had significantly lower residual gradients compared with BE-THVs, while self-expanding (SE)-RDVs had significantly higher residual gradients compared with SE-THVs. CONCLUSIONS: In a large all-comers' registry, TAVR with current-generation THVs was associated with improved in-hospital outcomes compared with SAVR with current-generation RDVs. The pacemaker rate is significantly higher with TAVR. Post-procedural hemodynamic function varied between individual RDVs and THVs.

Bicuspid Aortic Valve Morphology and Outcomes After Transcatheter Aortic Valve Replacement.

BACKGROUND: Bicuspid aortic stenosis accounts for almost 50% of patients undergoing surgical aortic valve replacement in the younger patients. Expanding the indication of transcatheter aortic valve replacement (TAVR) toward lower-risk and younger populations will lead to increased use of TAVR for patients with bicuspid aortic valve (BAV) stenosis despite the exclusion of bicuspid anatomy in all pivotal clinical trials. OBJECTIVES: This study sought to evaluate the association of BAV morphology and outcomes of TAVR with the new-generation devices. METHODS: Patients with BAV confirmed by central core laboratory computed tomography (CT) analysis were included from the international multicenter BAV TAVR registry. BAV morphology including the number of raphe, calcification grade in raphe, and leaflet calcium volume were assessed with CT analysis in a masked fashion. Primary outcomes were all-cause mortality at 1 and 2 years, and secondary outcomes included 30-day major endpoints and procedural complications. RESULTS: A total of 1,034 CT-confirmed BAV patients with a mean age of 74.7 years and Society of Thoracic Surgeons score of 3.7% underwent TAVR with contemporary devices (n = 740 with Sapien 3; n = 188 with Evolut R/Pro; n = 106 with others). All-cause 30-day, 1-year, and 2-year mortality was 2.0%, 6.7%, and 12.5%, respectively. Multivariable analysis identified calcified raphe and excess leaflet calcification (defined as more than median calcium volume) as independent predictors of 2-year all-cause mortality. Both calcified raphe plus excess leaflet calcification were found in 269 patients (26.0%), and they had significantly higher 2-year all-cause mortality than those with 1 or none of these morphological features (25.7% vs. 9.5% vs. 5.9%; log-rank p < 0.001). Patients with both morphological features had higher rates of aortic root injury (p < 0.001), moderate-to-severe paravalvular regurgitation (p = 0.002), and 30-day mortality (p = 0.016). CONCLUSIONS: Outcomes of TAVR in bicuspid aortic stenosis depend on valve morphology. Calcified raphe and excess leaflet calcification were associated with increased risk of procedural complications and midterm mortality. (Bicuspid Aortic Valve Stenosis Transcatheter Aortic Valve Replacement Registry; NCT03836521).

4D flow CMR analysis comparing patients with anatomically shaped aortic sinus prostheses, tube prostheses and healthy subjects introducing the wall shear stress gradient: a case control study.

BACKGROUND: Anatomically pre-shaped sinus prostheses (SP) were developed to mimic the aortic sinus with the goal to preserve near physiological hemodynamic conditions after valve-sparing aortic root replacement. Although SP have shown more physiological flow patterns, a comparison to straight tube prosthesis and the analysis of derived quantitative parameters is lacking. Hence, this study sought to analyze differences in aortic wall shear stress (WSS) between anatomically pre-shaped SP, conventional straight tube prostheses (TP), and age-matched healthy subjects) using time-resolved 3-dimensional flow cardiovascular magnetic resonance (4D Flow CMR). Moreover, the WSS gradient was introduced and analyzed regarding its sensitivity to detect changes in hemodynamics and its dependency on the expression of secondary flow patterns. METHODS: Twelve patients with SP (12 male, 62 ± 9yr), eight patients with TP (6 male, 59 ± 9yr), and twelve healthy subjects (2 male, 55 ± 6yr) were examined at 3 T with a 4D Flow CMR sequence in this case control study. Six analysis planes were placed in the thoracic aorta at reproducible landmarks. The following WSS parameters were recorded: WSSavg (spatially averaged over the contour at peak systole), max. WSSseg (maximum segmental WSS), min. WSSseg (minimum segmental WSS) and the WSS Gradient, calculated as max. WSSseg - min. WSSseg. Kruskal-Wallis- and Mann-Whitney-U-Test were used for statistical comparison of groups. Occurrence and expression of secondary flow patterns were evaluated and correlated to WSS values using Spearman's correlation coefficient. RESULTS: In the planes bordering the prosthesis all WSS values were significantly lower in the SP compared to the TP, approaching the physiological optimum of the healthy subjects. The WSS gradient showed significantly different values in the four proximally localized contours when comparing both prostheses with healthy subjects. Strong correlations between an elevated WSS gradient and secondary flow patterns were found in the ascending aorta and the aortic arch. CONCLUSION: Overall, the SP has a positive impact on WSS, most pronounced at the site and adjacent to the prosthesis. The WSS gradient differed most obviously and the correlation of the WSS gradient with the occurrence of secondary flow patterns provides further evidence for linking disturbed flow, which was markedly increased in patients compared to healthy sub jects, to degenerative remodeling of the vascular wall.