Management and risk of postoperative bleeding in patients with low-dose antiplatelet aspirin medication during endoscopic endonasal surgery for pituitary adenomas.

BACKGROUND: To analyze the risk of postoperative bleeding following endoscopic endonasal transsphenoidal surgery (EETS) for treatment of pituitary adenomas (PA) in patients with short-term discontinuation of low-dose aspirin, if required for prevention of artherothrombotic disease (ATD). METHODS: Patients with preoperative aspirin medication were identified in this single-center retrospective analysis of consecutive patients with PA, who underwent EETS between December 2008 and June 2022. Aspirin was discontinued perioperatively less than 2 days, > 2 and < 4 days, and > 4 and < 7 days according to the assumed risk of perioperative ATD. For those patients, the rate of postoperative bleeding, which required surgery, was compared to patients without aspirin. RESULTS: Forty-five (14.8%) out of 304 patients underwent EETS with short-term perioperative aspirin discontinuation. Thirty-six (80%) patients discontinued aspirin < 2 days, 6 (13.3%) patients > 2 and < 4 days, and 3 patients (6.7%) > 4 but < 7 days. Postoperative bleeding rate was not increased in patients with short-term perioperative aspirin discontinuation. One patient (0.3%) without perioperative aspirin medication underwent revision surgery for treatment of postoperative hemorrhage with suprasellar extension. Eight patients (2.6%) had postoperative epistaxis (1 patient (0.3%) with short-term discontinuation and 7 patients (2.3%) without aspirin). Patients with perioperative aspirin were significantly older (68.3 ± 8.6 vs. 57.9 ± 14.1; p < 0.01) and had a significantly lower rate of hormonally active tumors (11.1% vs. 25.1%; p < 0.05) compared to patients without aspirin. No differences were found for tumor characteristics (tumor extension, tumor volume, largest diameter) between both groups. CONCLUSION: Short-term discontinuation of low-dose aspirin was not associated with increased rate of postoperative bleeding in patients, who underwent EETS for treatment of PA.

Influence of Culprit Lesion Intervention on Outcomes in Infarct-Related Cardiogenic Shock With Cardiac Arrest.

BACKGROUND: Cardiac arrest (CA) is common in patients with infarct-related cardiogenic shock (CS). OBJECTIVES: The goal of this study was to identify the characteristics and outcomes of culprit lesion percutaneous coronary intervention (PCI) of patients with infarct-related CS stratified according to CA in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) randomized trial and registry. METHODS: Patients with CS with and without CA from the CULPRIT-SHOCK study were analyzed. All-cause death or severe renal failure leading to renal replacement therapy within 30 days and 1-year death were assessed. RESULTS: Among 1,015 patients, 550 (54.2%) had CA. Patients with CA were younger, more frequently male, had lower rates of peripheral artery disease, a glomerular filtration rate <30 mL/min, and left main disease, and they presented more often with clinical signs of impaired organ perfusion. The composite of all-cause death or severe renal failure within 30 days occurred in 51.2% of patients with CA vs 48.5% in non-CA patients (P = 0.39) and 1-year death in 53.8% vs 50.4% (P = 0.29), respectively. In a multivariate analysis, CA was an independent predictor of 1-year mortality (HR: 1.27; 95% CI: 1.01-1.59). In the randomized trial, culprit lesion-only PCI was superior to immediate multivessel PCI in patients both with and without CA (P for interaction = 0.6). CONCLUSIONS: More than 50% of patients with infarct-related CS had CA. These patients with CA were younger and had fewer comorbidities, but CA was an independent predictor of 1-year mortality. Culprit lesion-only PCI is the preferred strategy, both in patients with and without CA. (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock [CULPRIT-SHOCK]; NCT01927549).

Impact of moderate or severe left ventricular outflow tract calcification on clinical outcomes of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation with self- and balloon-expandable valves: a post hoc analysis from the SOLVE-TAVI trial.

BACKGROUND: Left ventricular outflow tract (LVOT) calcification has been associated with worse outcomes in patients undergoing transcatheter aortic valve implantation (TAVI) and may influence the selection of prosthetic valve type. AIMS: We aimed to evaluate the impact of LVOT calcification on outcomes after TAVI with a self-expanding valve (SEV) versus a balloon-expandable valve (BEV). METHODS: Patients of the SOLVE-TAVI trial, randomised to Edwards SAPIEN 3 or Medtronic Evolut R, were divided according to LVOT calcification into no/mild (≤1 calcium nodule extending <5 mm and covering <10% of the LVOT perimeter) and moderate/severe LVOT calcification groups. The primary endpoint was a composite of death, stroke, moderate/severe paravalvular regurgitation, permanent pacemaker implantation and annulus rupture at 30 days. Additional endpoints included all-cause and cardiovascular mortality at 1 year. RESULTS: Out of 416 eligible patients, moderate/severe LVOT calcification was present in 143 (34.4%). Moderate/severe LVOT calcification was associated with significantly longer fluoroscopy time and higher rates of pre- and post-dilation. Regardless of the LVOT calcification group, there was no significant difference in the primary endpoint associated with the valve type (no/mild LVOT calcification group: SEV 25.0% vs BEV 27.0%; hazard ratio [HR] 1.10, 95% confidence interval [95% CI]: 0.68-1.73; p=0.73 and moderate/severe LVOT calcification group: SEV 25.0% vs BEV 19.4%; HR 0.76, 95% CI: 0.38-1.61; p=0.49), no significant interaction between LVOT calcification and valve type (pint=0.29) and no differences between SEV vs BEV within LVOT calcification groups regarding 1-year all-cause and cardiovascular mortality. CONCLUSIONS: Moderate/severe LVOT calcification was associated with longer fluoroscopy time and an increased need for pre- and post-dilation, but not with a higher incidence of early and mid-term adverse clinical outcomes, regardless of valve type. (ClinicalTrials.gov: NCT02737150).

Soluble ST2 as a Potential Biomarker for Risk Assessment of Pulmonary Hypertension in Patients Undergoing TAVR?

BACKGROUND: Severe aortic valve stenosis (AS) is associated with pulmonary hypertension (PH) and has been shown to limit patient survival. Soluble suppression of tumorigenicity-2 (sST2) is a cardiovascular biomarker that has proven to be an important prognostic marker for survival in patients undergoing transcatheter aortic valve replacement (TAVR). The aim of this study was to assess the importance of the sST2 biomarker for risk stratification in patients with severe AS in presence or absence of PH. METHODS: In 260 patients with severe AS undergoing TAVR procedure, sST2 serum level concentrations were analyzed. Right heart catheter measurements were performed in 152 patients, with no PH detection in 43 patients and with PH detection in 109 patients. Correlation analyses according to Spearman, AUROC analyses and Kaplan-Meier curves were calculated. RESULTS: Patients with severe AS and PH showed significantly higher serum sST2 concentrations (p = 0.006). The sST2 cut-off value for non-PH patients regarding 1-year survival yielded 5521.15 pg/mL, whereas the cut-off value of PH patients was at a considerably higher level of 10,268.78 pg/mL. A cut-off value of 6990.12 pg/mL was related with a significant probability of PH presence. Survival curves showed that patients with severe AS and PH not only had higher 1-year mortality, but also that increased levels of sST2 plasma concentration were associated with earlier death. CONCLUSION: sST2 definitely has the potential to provide information about the presence of PH in patients with severe AS, in a noninvasive way.

Tumor necrosis factor alpha-an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?

BACKGROUND: Systemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre-interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF-α in TAVR. METHODS: A total of 431 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were drawn prior to intervention, 24 h post-intervention, 4, 5, and 7 days post-intervention, and 1, 3, and 6 months post-TAVR. RESULTS: In a univariate Cox proportional hazard analysis, plasma concentrations of TNF-α after 24 h and after 5 days were associated with mortality after 12 months (after 24 h: HR 1.002 (1.000-1.004), p = 0.028; after 5d: HR 1.003 (1.001-1.005), p = 0.013). This association remained significant even after correction for confounders in a multivariate Cox regression analysis. Additionally, cut-offs were calculated. Patients above the cut-off for TNF-α after 5d had a significantly worse 12-month mortality than patients below the cut-off (18.8% vs. 2.8%, p = 0.046). CONCLUSION: Plasma levels of TNF-α after 24 h and 5 days were independently associated with 12-month mortality in patients undergoing TAVR. Thus, TNF-α could represent a novel biomarker for enhanced risk stratification in these patients.

Investigating Aortic Valve Calcification via Isolation and Culture of T Lymphocytes using Feeder Cells from Irradiated Buffy Coat.

Calcific aortic valve disease (CAVD), an active disease process ranging from mild thickening of the valve to severe calcification, is associated with high mortality, despite new therapeutic options such as transcatheter aortic valve replacement (TAVR). The complete pathways that start with valve calcification and lead to severe aortic stenosis remain only partly understood. By providing a close representation of the aortic valve cells in vivo, the assaying of T lymphocytes from stenotic valve tissue could be an efficient way to clarify their role in the development of calcification. After surgical excision, the fresh aortic valve sample is dissected in small pieces and the T lymphocytes are cultured, cloned then analyzed using fluorescence activated cell sorting (FACS). The staining procedure is simple and the stained tubes can also be fixed using 0.5% of paraformaldehyde and analyzed up to 15 days later. The results generated from the staining panel can be used to track changes in T cell concentrations over time in relation to intervention and could easily be further developed to assess activation states of specific T cell subtypes of interest. In this study, we show the isolation of T cells, performed on fresh calcified aortic valve samples and the steps of analyzing T cell clones using flow cytometry to further understand the role of adaptive immunity in CAVD pathophysiology.

Transcatheter Tricuspid Valve Intervention in Patients With Previous Left Valve Surgery.

BACKGROUND: Scarce data exist on patients with previous left valve surgery (PLVS) undergoing transcatheter tricuspid valve intervention (TTVI). This study sought to investigate the procedural and early outcomes in patients with PLVS undergoing TTVI. METHODS: This was a subanalysis of the multicenter TriValve registry including 462 patients, 82 (18%) with PLVS. Data were analyzed according to the presence of PLVS in the overall cohort and in a propensity score-matched population including 51 and 115 patients with and without PLVS, respectively. RESULTS: Patients with PLVS were younger (72 ± 10 vs 78 ± 9 years; p < 0.01) and more frequently female (67.1% vs 53.2%; P = 0.02). Similar rates of procedural success (PLVS 80.5%; no-PLVS 82.1%; P = 0.73), and 30-day mortality (PLVS 2.4%, no-PLVS 3.4%; P = 0.99) were observed. After matching, there were no significant differences in both all-cause rehospitalisation (PLVS 21.1%, no-PLVS 26.5%; P = 0.60) and all-cause mortality (PLVS 9.8%, no-PLVS 6.7%; P = 0.58). At last follow-up (median 6 [interquartile range 1-12] months after the procedure), most patients (81.8%) in the PLVS group were in NYHA functional class I-II (P = 0.12 vs no-PLVS group), and TR grade was ≤ 2 in 82.6% of patients (P = 0.096 vs no-PVLS group). A poorer right ventricular function and previous heart failure hospitalization determined increased risks of procedural failure and poorer outcomes at follow-up, respectively. CONCLUSIONS: In patients with PLVS, TTVI was associated with high rates of procedural success and low early mortality. However, about one-third of patients required rehospitalisation or died at midterm follow-up. These results would support TTVI as a reasonable alternative to redo surgery in patients with PLVS and suggest the importance of earlier treatment to improve clinical outcomes.

IMPULSE: the impact of gender on the presentation and management of aortic stenosis across Europe.

AIMS: There is an increasing awareness of gender-related differences in patients with severe aortic stenosis and their outcomes after surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). METHODS: Data from the IMPULSE registry were analysed. Patients with severe aortic stenosis (AS) were enrolled between March 2015 and April 2017 and stratified by gender. A subgroup analysis was performed to assess the impact of age. RESULTS: Overall, 2171 patients were enrolled, and 48.0% were female. Women were characterised by a higher rate of renal impairment (31.7 vs 23.3%; p<0.001), were at higher surgical risk (EuroSCORE II: 4.5 vs 3.6%; p=0.001) and more often in a critical preoperative state (7.0vs 4.2%; p=0.003). Men had an increased rate of previous cardiac surgery (9.4 vs 4.7%; p<0.001) and a reduced left ventricular ejection fraction (4.9 vs 1.3%; p<0.001). Concomitant mitral and tricuspid valve disease was substantially more common among women. Symptoms were highly prevalent in both women and men (83.6 vs 77.3%; p<0.001). AVR was planned in 1379 cases. Women were more frequently scheduled to undergo TAVI (49.3 vs 41.0%; p<0.001) and less frequently for SAVR (20.3 vs 27.5%; p<0.001). CONCLUSIONS: The present data show that female patients with severe AS have a distinct patient profile and are managed in a different way to males. Gender-based differences in the management of patients with severe AS need to be taken into account more systematically to improve outcomes, especially for women.

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. CONCLUSIONS: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

Bacterial biofilms in infective endocarditis: an in vitro model to investigate emerging technologies of antimicrobial cardiovascular device coatings.

OBJECTIVE: In spite of the progress in antimicrobial and surgical therapy, infective endocarditis (IE) is still associated with a high morbidity and mortality. IE is characterized by bacterial biofilms of the endocardium, especially of the aortic and mitral valve leading to their destruction. About one quarter of patients with formal surgery indication cannot undergo surgery. This group of patients needs further options of therapy, but due to a lack of models for IE prospects of research are low. Therefore, the purpose of this project was to establish an in vitro model of infective endocarditis to allow growth of bacterial biofilms on porcine aortic valves, serving as baseline for further research. METHODS AND RESULTS: A pulsatile two-chamber circulation model was constructed that kept native porcine aortic valves under sterile, physiologic hemodynamic and temperature conditions. To create biofilms on porcine aortic valves the system was inoculated with Staphylococcus epidermidis PIA 8400. Aortic roots were incubated in the model for increasing periods of time (24 h and 40 h) and bacterial titration (1.5 × 104 CFU/mL and 1.5 × 105 CFU/mL) with 5 L cardiac output per minute. After incubation, tissue sections were analysed by fluorescence in situ hybridization (FISH) for direct visualization of the biofilms. Pilot tests for biofilm growth showed monospecies colonization consisting of cocci with time- and inocula-dependent increase after 24 h and 40 h (n = 4). In n = 3 experiments for 24 h, with the same inocula, FISH visualized biofilms with ribosome-containing, and thus metabolic active cocci, tissue infiltration and similar colonization pattern as observed by the FISH in human IE heart valves infected by S. epidermidis. CONCLUSION: These results demonstrate the establishment of a novel in vitro model for bacterial biofilm growth on porcine aortic roots mimicking IE. The model will allow to identify predilection sites of valves for bacterial adhesion and biofilm growth and it may serve as baseline for further research on IE therapy and prevention, e.g. the development of antimicrobial transcatheter approaches to IE.

Transcatheter therapies for severe tricuspid regurgitation. Quo vadis?

Moderate-to-severe tricuspid regurgitation (TR) is common and is associated with a poor prognosis. To date, most patients are undertreated; therefore, transcatheter options could be clinically impactful in those who are denied surgery. Several transcatheter solutions have been developed that address the problem via leaflet enhancement, annuloplasty, or heterotopic implantation of self-expandable or balloon-expandable valves in the caval veins. A comprehensive patient evaluation, based on multimodality imaging techniques for a better understanding of the valvular pathology and TR mechanism, remains paramount for an appropriate device selection. To date, several trials have shown the feasibility and safety of a multitude of devices in this setting, but data from randomized clinical trials regarding clinical benefit based on hard endpoints are still lacking. Although the optimal patient profile and timing of intervention remain under investigation, data from available studies indicate that an earlier treatment referral, before onset of irreversible right ventricular remodeling, could be beneficial. This review discusses the present landscape and future implications of transcatheter therapies for severe TR.

Differences in the presentation and management of patients with severe aortic stenosis in different European centres.

BACKGROUND: An investigation into differences in the management and treatment of severe aortic stenosis (AS) between Germany, France and the UK may allow benchmarking of the different healthcare systems and identification of levers for improvement. METHODS: Patients with a diagnosis of severe AS under management at centres within the IMPULSE and IMPULSE enhanced registries were eligible. RESULTS: Data were collected from 2052 patients (795 Germany; 542 France; 715 UK). Patients in Germany were older (79.8 years), often symptomatic (89.5%) and female (49.8%) and had a lower EF (53.8%) than patients in France and UK. Comorbidities were more common and they had a higher mean Euroscore II.Aortic valve replacement (AVR) was planned within 3 months in 70.2%. This was higher (p<0.001) in Germany than France/ UK. Of those with planned AVR, 82.3% received it within 3 months with a gradual decline (Germany>France> UK; p<0.001). In 253 patients, AVR was not performed, despite planned. Germany had a strong transcatheter aortic valve implantation (TAVI) preference (83.2%) versus France/ UK (p<0.001). Waiting time for TAVI was shorter in Germany (24.9 days) and France (19.5 days) than UK (40.3 days).Symptomatic patients were scheduled for an AVR in 79.4% (Germany> France> UK; p<0.001) and performed in 83.6% with a TAVI preference (73.1%). 20.4% of the asymptomatic patients were intervened. CONCLUSION: Patients in Germany had more advanced disease. The rate of intervention within 3 months after diagnosis was startlingly low in the UK. Asymptomatic patients without a formal indication often underwent an intervention in Germany and France.

Impact of selected comorbidities on the presentation and management of aortic stenosis.

BACKGROUND: Contemporary data regarding the impact of comorbidities on the clinical presentation and management of patients with severe aortic stenosis (AS) are scarce. METHODS: Prospective registry of severe patients with AS across 23 centres in nine European countries. RESULTS: Of the 2171 patients, chronic kidney disease (CKD 27.3%), left ventricular ejection fraction (LVEF) <50% (22.0%), atrial fibrillation (15.9%) and chronic obstructive pulmonary disease (11.4%) were the most prevalent comorbidities (49.3% none, 33.9% one and 16.8% ≥2 of these). The decision to perform aortic valve replacement (AVR) was taken in a comparable proportion (67%, 72% and 69%, in patients with 0, 1 and ≥2 comorbidities; p=0.186). However, the decision for TAVI was more common with more comorbidities (35.4%, 54.0% and 57.0% for no, 1 and ≥2; p<0.001), while the decision for surgical AVR (SAVR) was decreased with increasing comorbidity burden (31.9%, 17.4% and 12.3%; p<0.001). The proportion of patients with planned AVRs that were performed within 3 months was significantly higher in patients with 1 or ≥2 comorbidities than in those without (8.7%, 10.0% and 15.7%; p<0.001). Furthermore, the mean time to AVR was significantly shorter in patients with one (30.5 days) or ≥2 comorbidities (30.8 days) than in those without (35.7 days; p=0.012). Patients with reduced LVEF tended to be offered an AVR more frequently and with a shorter delay while patients with CKD were less frequently treated. CONCLUSIONS: Comorbidities in severe patients with AS affect the presentation and management of patients with severe AS. TAVI was offered more often than SAVR and performed within a shorter time period.

Virome Sequencing in Patients With Myocarditis.

BACKGROUND: Polymerase chain reaction analyses of cardiac tissues have detected viral sequences in up to 67% of cases of myocarditis. However, viruses have not been implicated in giant cell myocarditis (GCM). Furthermore, efforts to detect viruses implicated in myocarditis have been unsuccessful in more accessible samples such as peripheral blood. METHODS: We used Virome Capture Sequencing for Vertbrate Viruses (VirCapSeq-VERT), a method that simultaneously screens for all known vertebrate viruses, to investigate viruses in 33 patients with myocarditis. We investigated peripheral blood mononuclear cells (n=24), plasma (n=27), endomyocardial biopsies (n=2), and cardiac tissue samples from explanted hearts (n=13). RESULTS: Nine patients (27%) had GCM and 4 patients (13%) had fulminant myocarditis. We found the following viruses in the blood of patients with myocarditis: Epstein Barr virus (n=11, 41%), human pegivirus (n=1, 4%), human endogenous retrovirus K (n=27, 100%), and anellovirus (n=15, 56%). All tissue samples from fulminant myocarditis (n=2) and GCM (n=13) contained human endogenous retrovirus K. CONCLUSIONS: No nucleic acids from viruses previously implicated in myocarditis or other human illnesses were detected in relevant amounts in cardiac tissue samples from GCM or in blood samples from other types of myocarditis. These findings do not exclude a role for viral infection in GCM but do suggest that if viruses are implicated, the mechanism is likely to be indirect rather than due to cytotoxic infection of myocardium.

Treatment of Severe TRIcuspid Regurgitation in Patients with Advanced Heart Failure with CAval Vein Implantation of the Edwards Sapien XT VALve (TRICAVAL): a randomised controlled trial.

AIMS: The aim of our study was to compare the impact of implantation of a balloon-expandable transcatheter valve into the inferior vena cava (CAVI) on exercise capacity with optimal medical therapy (OMT) in patients with severe tricuspid regurgitation (TR) and high surgical risk. METHODS AND RESULTS: Twenty-eight patients were randomised to OMT (n=14) or CAVI (n=14). The primary endpoint was maximal oxygen uptake at the three-month follow-up. Secondary endpoints included six-minute walk test, NYHA class, NT-proBNP levels, right heart function, unscheduled heart failure hospitalisation, and quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Patients underwent follow-up examinations one, three, six, and twelve months after randomisation. Maximal oxygen uptake did not change significantly in either group after three months and there was no difference between the OMT and CAVI groups (-0.1±1.8 ml∙kg-1∙min-1 vs -1.0±1.6 ml∙kg-1∙min-1, p=0.4995). Compared to baseline, CAVI improved NYHA class, dyspnoea, and quality of life after three months. However, there were no statistically significant differences in the secondary endpoints between the groups. Four periprocedural complications occurred after CAVI, resulting in open heart surgery. Four patients in the OMT group and eight patients (including four after conversion to surgery) in the CAVI group died from right heart failure, sepsis or haemorrhage. CONCLUSIONS: CAVI did not result in a superior functional outcome compared to OMT. Due to an unexpectedly high rate of valve dislocations, the study was stopped for safety reasons.

Assessment of intermediate coronary lesions by fractional flow reserve and quantitative flow ratio in patients with small-vessel disease.

BACKGROUND: Quantitative flow ratio (QFR) has recently been introduced as a novel, less-invasive, adenosine-free measure for functional coronary lesion assessment. Whether reference vessel dimensions affect functional lesion assessment is uncertain. METHODS: A total of 436 patients with 516 interrogated coronary vessels by means of FFR were included in the study. Patients were dichotomized according to the median reference vessel diameter (group 1: ≤2.8 mm and group 2: >2.8 mm). QFR analyses were performed offline at the institution's core laboratories. RESULTS: Reference vessel diameter was 2.5 [2.3-2.7] mm in group 1 and 3.3 [3.0-3.6] mm in group 2. Diameter stenosis (41.4 [36.4-47.6] % vs. 41.4 [36.4-45.7] %, p = .20) did not differ among groups. Median FFR values were lower in group 1 (0.87 [0.81-0.92]) as compared with group 2 (0.89 [0.84-0.93], p = .001). Consistently, QFR values were lower in group 1 (0.88 [0.82-0.92]) than in group 2 (0.91 [0.85-0.94], p = .001). The proportions of functionally significant coronary lesions as defined by FFR ≤0.80 were 24.1% and 14.2% in groups 1 and 2 (p = .005), and as defined by cQFR ≤0.80 20.4% and 11.8% (p = 0.009), respectively. In ROC analysis for an FFR ≤.80, the AUC was 0.89 (95% CI 0.85-0.93, p < .001) in group 1 and 0.81 (95% CI 0.76-0.86, p < .001) in group 2. CONCLUSIONS: These results suggest that QFR measurements are accurate irrespective of the reference vessel diameter. Future studies are needed to elucidate the higher percentage of functionally significant lesions observed in small vessels despite a similar angiographic lesion severity.

Incidence and outcome of peri-procedural transcatheter heart valve embolization and migration: the TRAVEL registry (TranscatheteR HeArt Valve EmboLization and Migration).

AIMS: Peri-procedural transcatheter valve embolization and migration (TVEM) is a rare but potentially devastating complication of transcatheter aortic valve implantation (TAVI). We sought to assess the incidence, causes, and outcome of TVEM in a large multicentre cohort. METHODS AND RESULTS: We recorded cases of peri-procedural TVEM in patients undergoing TAVI between January 2010 and December 2017 from 26 international sites. Peri-procedural TVEM occurred in 273/29 636 (0.92%) TAVI cases (age 80.8 ± 7.3 years; 53.8% female), of which 217 were to the ascending aorta and 56 to the left ventricle. The use of self-expanding or first-generation prostheses and presence of a bicuspid aortic valve were independent predictors of TVEM. Bail-out measures included repositioning attempts using snares or miscellaneous tools (41.0%), multiple valve implantations (83.2%), and conversion to surgery (19.0%). Using 1:4-propensity matching, we identified a cohort of 235 patients with TVEM (TVEMPS) and 932 patients without TVEM (non-TVEMPS). In the matched cohort, all-cause mortality was higher in TVEMPS than in non-TVEMPS at 30 days (18.6% vs. 4.9%; P < 0.001) and after 1 year (30.5% vs. 16.6%; P < 0.001). Major stroke was more frequent in TVEMPS at 30 days (10.6% vs. 2.8%; P < 0.001), but not at 1 year (4.6% vs. 1.9%; P = 0.17). The need for emergent cardiopulmonary support, major stroke at 30 days, and acute kidney injury Stages 2 and 3 increased the risk of 1-year mortality, whereas a better renal function at baseline was protective. CONCLUSION: Transcatheter valve embolization and migration occurred in approximately 1% and was associated with increased morbidity and mortality.

Transcatheter valve-in-valve implantation (VinV-TAVR) for failed surgical aortic bioprosthetic valves.

OBJECTIVE: We sought to investigate the procedural and hemodynamic outcome after valve-in-valve transcatheter aortic valve replacement (VinV-TAVR) for different surgical (SBV) and transcatheter (TAVR) bioprosthetic valves. METHODS AND RESULTS: 223 patients (76 ± 11years, STS-Score 8.3 ± 10.1) suffering from SBV failure treated with VinV-TAVR were enrolled at 6 centers across Germany. At time of the intervention, the majority of patients were in NYHA-class ≥ III (88%, n = 180). Failure mode of the SBVs was either stenosis, regurgitation (AR) or a combination of both in 85 (38%), 76 (34%) and 62 (28%) patients, respectively. 138 (62%) patients were treated with first generation TAVR valves (Edwards Sapien XT or CoreValve). Second generation valves were implanted in 85 (38%) patients (Sapien 3, Medtronic CoreValve Evolut, SJM-Portico, JenaValve). VinV-TAVR was associated with high procedural success rate, conversion to surgery was necessary in 3 (2%) patients. After VinV-TAVR procedure, 4 (2%) patients suffered from ≥ moderate AR. In 6 (3%) patients a second valve was implanted due to mispositioning of the first valve and subsequent severe paravalvular AR. Coronary obstruction was observed in 4 (2%) patients. Major bleeding and cerebrovascular complications (according to VARC) were reported in 3 (1%) and 4 (2%) patients at 30 days. Post-interventionally, 44/178 (25%) patients evidenced a mean pressure gradient (mPG) ≥ 20 mmHg. Residual stenosis was not associated with increased mortality (HR 0.39; 95% CI 0.13-1.22; p = 0.11). CONCLUSION: In VinV-TAVR for SBV-failure is a safe procedure resulting in hemodynamic improvement in the majority of patients. Residual stenosis is a common finding which can be observed in 1/4 of patients undergoing VinV-TAVR. However, this condition is not associated with increased 1-year-mortality.

Outcomes of transcatheter mitral valve replacement for degenerated bioprostheses, failed annuloplasty rings, and mitral annular calcification.

Aims: We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring (ViR)], and severe mitral annular calcification [valve-in-mitral annular calcification (ViMAC)]. Methods and results: From the TMVR multicentre registry, procedural and clinical outcomes of ViV, ViR, and ViMAC were compared according to Mitral Valve Academic Research Consortium (MVARC) criteria. A total of 521 patients with mean Society of Thoracic Surgeons score of 9.0 ± 7.0% underwent TMVR (322 patients with ViV, 141 with ViR, and 58 with ViMAC). Trans-septal access and the Sapien valves were used in 39.5% and 90.0%, respectively. Overall technical success was excellent at 87.1%. However, left ventricular outflow tract obstruction occurred more frequently after ViMAC compared with ViR and ViV (39.7% vs. 5.0% vs. 2.2%; P < 0.001), whereas second valve implantation was more frequent in ViR compared with ViMAC and ViV (12.1% vs. 5.2% vs. 2.5%; P < 0.001). Accordingly, technical success rate was higher after ViV compared with ViR and ViMAC (94.4% vs. 80.9% vs. 62.1%; P < 0.001). Compared with ViMAC and ViV groups, ViR group had more frequent post-procedural mitral regurgitation ≥moderate (18.4% vs. 13.8% vs. 5.6%; P < 0.001) and subsequent paravalvular leak closure (7.8% vs. 0.0% vs. 2.2%; P = 0.006). All-cause mortality was higher after ViMAC compared with ViR and ViV at 30 days (34.5% vs. 9.9% vs. 6.2%; log-rank P < 0.001) and 1 year (62.8% vs. 30.6% vs. 14.0%; log-rank P < 0.001). On multivariable analysis, patients with failed annuloplasty rings and severe MAC were at increased risk of mortality after TMVR [ViR vs. ViV, hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.27-3.12; P = 0.003; ViMAC vs. ViV, HR 5.29, 95% CI 3.29-8.51; P < 0.001]. Conclusion: The TMVR provided excellent outcomes for patients with degenerated bioprostheses despite high surgical risk. However, ViR and ViMAC were associated with higher rates of adverse events and mid-term mortality compared with ViV.

Comparison of resting distal to aortic coronary pressure with angiography-based quantitative flow ratio.

BACKGROUND: Quantitative flow ratio (QFR) is a novel, adenosine-free method for functional coronary lesion interrogation, which is based on 3-dimensional quantitative coronary angiography and computational algorithms. Data on QFR in all-comer patients with intermediate coronary lesions are scarce, and the diagnostic performance in comparison to resting distal to aortic coronary pressure (Pd/Pa) ratio unknown. METHODS: A total of 436 patients with 516 vessels undergoing FFR measurements were included in the analysis. Diagnostic performance of QFR, distal to aortic coronary pressure (Pd/Pa) ratio, and anatomic indices versus FFR was assessed. RESULTS: FFR ≤0.80 was measured in 19.4% of interrogated vessels. QFR significantly correlated with FFR (r = 0.82, p < 0.001) with good agreement between QFR and FFR (mean difference 0.011, 95% CI 0.008-0.015). The AUC for an FFR ≤0.80 was 0.86 (95% CI 0.83-0.89, p < 0.001) for QFR, 0.76 (0.72-0.80, p < 0.001) for resting Pd/Pa ratio, and 0.63 (0.59-0.67, p < 0.001) for diameter stenosis. The diagnostic accuracy for identifying an FFR ≤0.80 was 93.4% for QFR, 84.3% for resting Pd/Pa ratio, and 80.4% for diameter stenosis. CONCLUSIONS: QFR provides a novel diagnostic tool for functional coronary lesion assessment with superior diagnostic accuracy as compared with resting Pd/Pa ratio and anatomic indices. Future studies are needed to determine the non-inferiority of QFR analysis to FFR assessment with respect to clinical outcomes.