Transcatheter or surgical aortic valve implantation: 10-year outcomes of the NOTION trial.

BACKGROUND AND AIMS: Transcatheter aortic valve implantation (TAVI) has become a viable treatment option for patients with severe aortic valve stenosis across a broad range of surgical risk. The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomize patients at lower surgical risk to TAVI or surgical aortic valve replacement (SAVR). The aim of the present study was to report clinical and bioprosthesis outcomes after 10 years. METHODS: The NOTION trial randomized 280 patients to TAVI with the self-expanding CoreValve (Medtronic Inc.) bioprosthesis (n = 145) or SAVR with a bioprosthesis (n = 135). The primary composite outcome was the risk of all-cause mortality, stroke, or myocardial infarction. Bioprosthetic valve dysfunction (BVD) was classified as structural valve deterioration (SVD), non-structural valve dysfunction (NSVD), clinical valve thrombosis, or endocarditis according to Valve Academic Research Consortium-3 criteria. Severe SVD was defined as (i) a transprosthetic gradient of 30 mmHg or more and an increase in transprosthetic gradient of 20 mmHg or more or (ii) severe new intraprosthetic regurgitation. Bioprosthetic valve failure (BVF) was defined as the composite rate of death from a valve-related cause or an unexplained death following the diagnosis of BVD, aortic valve re-intervention, or severe SVD. RESULTS: Baseline characteristics were similar between TAVI and SAVR: age 79.2 ± 4.9 years and 79.0 ± 4.7 years (P = .7), male 52.6% and 53.8% (P = .8), and Society of Thoracic Surgeons score < 4% of 83.4% and 80.0% (P = .5), respectively. After 10 years, the risk of the composite outcome all-cause mortality, stroke, or myocardial infarction was 65.5% after TAVI and 65.5% after SAVR [hazard ratio (HR) 1.0; 95% confidence interval (CI) 0.7-1.3; P = .9], with no difference for each individual outcome. Severe SVD had occurred in 1.5% and 10.0% (HR 0.2; 95% CI 0.04-0.7; P = .02) after TAVI and SAVR, respectively. The cumulative incidence for severe NSVD was 20.5% and 43.0% (P < .001) and for endocarditis 7.2% and 7.4% (P = 1.0) after TAVI and SAVR, respectively. No patients had clinical valve thrombosis. Bioprosthetic valve failure occurred in 9.7% of TAVI and 13.8% of SAVR patients (HR 0.7; 95% CI 0.4-1.5; P = .4). CONCLUSIONS: In patients with severe AS and lower surgical risk randomized to TAVI or SAVR, the risk of major clinical outcomes was not different 10 years after treatment. The risk of severe bioprosthesis SVD was lower after TAVR compared with SAVR, while the risk of BVF was similar.

Transcatheter Aortic Valve Implantation in Low-Risk Tricuspid or Bicuspid Aortic Stenosis: The NOTION-2 Trial.

BACKGROUND AND AIMS: Transcatheter aortic valve implantation (TAVI) has become the first choice to treat older patients with severe symptomatic aortic stenosis (AS). This study aimed to compare TAVI with surgery in low-risk patients ≤ 75 years of age, including both tricuspid and bicuspid AS. METHODS: The NOTION-2 trial enrolled and 1:1 randomized low-risk patients aged ≤ 75 years with severe symptomatic AS to TAVI or surgery. The primary endpoint was a composite of all-cause mortality, stroke or rehospitalization (related to the procedure, valve or heart failure) at 12 months. RESULTS: A total of 370 patients were enrolled with a mean age of 71.1 years and a median Society of Thoracic Surgeons risk score of 1.1%. A total of 100 patients had bicuspid AS. The 1-year incidence of the primary endpoint was 10.2% in the TAVI group and 7.1% in the surgery group (absolute risk difference 3.1%; 95% confidence interval [CI], -2.7% to 8.8%; hazard ratio (HR) 1.4, 95% CI: 0.7 to 2.9; p=0.3). Patients with TAVI, when compared to surgery, had lower risk of major bleeding and new-onset atrial fibrillation and higher risk of non-disabling stroke, permanent pacemaker implantation and moderate-or-greater paravalvular regurgitation. The risk of the primary composite endpoint was 8.7% and 8.3% in patients with tricuspid AS (HR 1.0, 95% CI: 0.5 to 2.3) and 14.3% and 3.9% in patients with bicuspid AS (HR 3.8, 95% CI: 0.8 to 18.5) treated with TAVI or surgery, respectively (P for interaction=0.1). CONCLUSIONS: Among low-risk patients aged ≤ 75 years with severe symptomatic AS, the rate of the composite of death, stroke, or rehospitalization at one year was similar between TAVI and surgery. TAVI outcomes in young bicuspid AS patients warrant caution and should be further investigated. (NOTION-2, ClinicalTrials.gov, NCT02825134).

Extent of cardiac damage and hospitalization burden in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Cardiac damage has gained increasing attention as a valid prognostic marker of mortality after transcatheter aortic valve replacement (TAVR). However, studies investigating the possible association between cardiac damage and hospitalization burden in TAVR patients are lacking. AIMS: This study aimed to investigate the impact of baseline cardiac damage on the hospitalization burden before, during, and after TAVR in an all-comers population. METHODS: All consecutive patients who underwent TAVR between 2016 and 2020 were included. Electronic medical records of all patients were examined to validate cardiovascular (CV) and heart failure (HF) related hospitalizations from 6 months before to 1 year after TAVR. Baseline cardiac damage was defined according to the staging classification by Généreux et al. RESULTS: Among 1397 TAVR patients, 94 (6.7%) had stage 0, 368 (26.4%) stage 1, 736 (52.7%) stage 2, 115 (8.2%) stage 3, and 84 (6.0%) stage 4 cardiac damage. Patients with more advanced cardiac damage at baseline had more HF hospitalizations within 6 months before TAVR (p < 0.01) and with a longer length of stay (LoS) (p < 0.01). Regarding the index TAVR admission, there was no difference in procedure time (p = 0.26) or LoS (p = 0.18) between groups. Still, TAVR patients with more advanced baseline cardiac damage had a higher risk of CV and HF rehospitalization after TAVR (p < 0.05). CONCLUSIONS: Baseline cardiac damage in patients undergoing TAVR has an impact on the pre- and post-procedural cardiovascular hospitalization burden. However, the cardiac damage status does not affect the TAVR procedure time or index TAVR admission length of stay.

Liraglutide 3.0 mg once daily for the treatment of overweight and obesity in patients hospitalised at a forensic psychiatric department: A 26-week open-label feasibility study.

INTRODUCTION: Overweight and obesity constitute a major concern among patients treated at forensic psychiatric departments. The present clinical feasibility study aimed at investigating the extent to which glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with once-daily liraglutide 3.0 mg could be a feasible pharmacological treatment of these conditions in patients with schizophrenia spectrum disorders hospitalised in forensic psychiatry. METHODS: The 26-week, open-label feasibility study included participants aged 18-65 years diagnosed with a severe mental illness and hospitalised at a forensic psychiatric department. At the time of inclusion, all participants fulfilled the indication for using liraglutide as a treatment for overweight and obesity. Participants' baseline examinations were followed by a 26-week treatment period with liraglutide injection once daily according to a fixed uptitration schedule of liraglutide, with a target dose of 3.0 mg. Each participant attended seven visits to evaluate the efficacy and adverse events. The primary endpoint was the number of "completers", with adherence defined as >80% injections obtained in the period, weeks 12-26. Determining whether liraglutide is a feasible treatment was pre-defined to a minimum of 75% completers. RESULTS: Twenty-four participants were included in the study. Sex, male = 19 (79.2%). Mean age: 42.3 [25th and 75th percentiles: 39.1; 48.4] years; body mass index (BMI): 35.7 [31.7; 37.5] kg/m2; glycated haemoglobin (HbA1c): 37 [35; 39] mmol/mol. Eleven out of 24 participants (46%) completed the study. For the completers, the median net body weight loss after 26 weeks of participation was -11.4 kg [-15.4; -5.9]. The net difference in HbA1C and BMI was -2.0 mmol/mol [-4; -1] and -3.6 kg/m2 [-4.7; -1.8], respectively. The weight change and reduction in HbA1c and BMI were all statistically significant from baseline. CONCLUSION: The study did not confirm our hypothesis that liraglutide is a feasible treatment for a minimum of 75% of the patients initiating treatment with liraglutide while hospitalised in a forensic psychiatric department. The high dropout rate may be due to the non-naturalistic setting of the clinical trial. For the proportion of patients compliant with the medication, liraglutide 3.0 mg was an efficient treatment for overweight.

Transcatheter versus surgical aortic valve replacement in lower-risk and higher-risk patients: a meta-analysis of randomized trials.

AIMS: Additional randomized clinical trial (RCT) data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) is available, including longer term follow-up. A meta-analysis comparing TAVI to SAVR was performed. A pragmatic risk classification was applied, partitioning lower-risk and higher-risk patients. METHODS AND RESULTS: The main endpoints were death, strokes, and the composite of death or disabling stroke, occurring at 1 year (early) or after 1 year (later). A random-effects meta-analysis was performed. Eight RCTs with 8698 patients were included. In lower-risk patients, at 1 year, the risk of death was lower after TAVI compared with SAVR [relative risk (RR) 0.67; 95% confidence interval (CI) 0.47 to 0.96, P = 0.031], as was death or disabling stroke (RR 0.68; 95% CI 0.50 to 0.92, P = 0.014). There were no differences in strokes. After 1 year, in lower-risk patients, there were no significant differences in all main outcomes. In higher-risk patients, there were no significant differences in main outcomes. New-onset atrial fibrillation, major bleeding, and acute kidney injury occurred less after TAVI; new pacemakers, vascular complications, and paravalvular leak occurred more after TAVI. CONCLUSION: In lower-risk patients, there was an early mortality reduction with TAVI, but no differences after later follow-up. There was also an early reduction in the composite of death or disabling stroke, with no difference at later follow-up. There were no significant differences for higher-risk patients. Informed therapy decisions may be more dependent on the temporality of events or secondary endpoints than the long-term occurrence of main clinical outcomes.

Routine revascularization with percutaneous coronary intervention in patients with coronary artery disease undergoing transcatheter aortic valve implantation - the third nordic aortic valve intervention trial - NOTION-3.

BACKGROUND: Coronary artery disease (CAD) frequently coexists with severe aortic valve stenosis (AS) in patients planned for transcatheter aortic valve implantation (TAVI). How to manage CAD in this patient population is still an unresolved question. In particular, it is still not known whether fractional flow reserve (FFR) guided revascularization with percutaneous coronary intervention (PCI) is superior to medical treatment for CAD in terms of clinical outcomes. STUDY DESIGN: The third Nordic Aortic Valve Intervention (NOTION-3) Trial is an open-label investigator-initiated, multicenter multinational trial planned to randomize 452 patients with severe AS and significant CAD to either FFR-guided PCI or medical treatment, in addition to TAVI. Patients are eligible for the study in the presence of at least 1 significant PCI-eligible coronary stenosis. A significant stenosis is defined as either FFR ≤0.80 and/or diameter stenosis >90%. The primary end point is a composite of first occurring all-cause mortality, myocardial infarction, or urgent revascularization (PCI or coronary artery bypass graft performed during unplanned hospital admission) until the last included patient have been followed for 1 year after the TAVI. SUMMARY: NOTION-3 is a multicenter, multinational randomized trial aiming at comparing FFR-guided revascularization vs medical treatment of CAD in patients with severe AS planned for TAVI.

Impact of implantation technique on conduction disturbances for TAVR with the self-expanding portico/navitor valve.

BACKGROUND: Use of a right-left (R-L) cusp overlap view for transcatheter aortic valve replacement (TAVR) with self-expanding valves has recently been proposed aiming to reduce permanent pacemaker implantation (PPMI). An objective, data-driven explanation for this observation is missing. AIMS: To assess the impact of different implantation techniques on the risk of PPMI following TAVR with the Portico/NavitorTM transcatheter heart valve (THV; Abbott). METHODS: A TAVR-population treated with Portico/NavitorTM had the THV implanted in a right versus left anterior oblique (RAO/LAO) fluoroscopic view with no parallax in the delivery system. The impact of these different implantation views on the spatial relationship between THV and native aortic annulus and the risk of conduction disturbances and PPMI after TAVR was studied. RESULTS: A total of 366 matched TAVR patients were studied: 183 in the RAO group and 183 in the LAO group. The degree of aortic annulus plane tilt was significantly smaller in the RAO versus LAO group (median: 0° vs. 23°, p < 0.001), with no plane tilt in 105 out of 183 cases (57.3%) in the RAO group. At 30 days after TAVR, the overall PPMI and guideline-directed PPMI rates were 12.6% versus 18.0% (p = 0.15) and 8.2% versus 15.3% (p = 0.04) in the RAO versus LAO group, respectively. CONCLUSIONS: Use of a R-L cusp overlap (RAO-caudal) view for implantation of the Portico/NavitorTM valve results in less tilt of the native aortic annulus plane and a clear trend toward a lower 30-day PPMI rate as compared to TAVR using the conventional LAO implantation view.

Eight-year outcomes for patients with aortic valve stenosis at low surgical risk randomized to transcatheter vs. surgical aortic valve replacement.

AIMS: The aims of the study were to compare clinical outcomes and valve durability after 8 years of follow-up in patients with symptomatic severe aortic valve stenosis at low surgical risk treated with either transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). METHODS AND RESULTS: In the NOTION trial, patients with symptomatic severe aortic valve stenosis were randomized to TAVI or SAVR. Clinical status, echocardiography, structural valve deterioration, and failure were assessed using standardized definitions. In total, 280 patients were randomized to TAVI (n = 145) or SAVR (n = 135). Baseline characteristics were similar, including mean age of 79.1 ± 4.8 years and a mean STS score of 3.0 ± 1.7%. At 8-year follow-up, the estimated risk of the composite outcome of all-cause mortality, stroke, or myocardial infarction was 54.5% after TAVI and 54.8% after SAVR (P = 0.94). The estimated risks for all-cause mortality (51.8% vs. 52.6%; P = 0.90), stroke (8.3% vs. 9.1%; P = 0.90), or myocardial infarction (6.2% vs. 3.8%; P = 0.33) were similar after TAVI and SAVR. The risk of structural valve deterioration was lower after TAVI than after SAVR (13.9% vs. 28.3%; P = 0.0017), whereas the risk of bioprosthetic valve failure was similar (8.7% vs. 10.5%; P = 0.61). CONCLUSIONS: In patients with severe aortic valve stenosis at low surgical risk randomized to TAVI or SAVR, there were no significant differences in the risk for all-cause mortality, stroke, or myocardial infarction, as well as the risk of bioprosthetic valve failure after 8 years of follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01057173.

Impact of early hospital discharge on clinical outcomes after transcatheter aortic valve implantation.

AIMS: Early discharge after transcatheter aortic valve implantation (TAVI) may potentially impact post-procedural safety of the patient. The study aim was to compare safety of TAVI in patients planned for fast track hospital stay with patients planned for standard hospital stay. METHODS AND RESULTS: All-comers patients undergoing transfemoral TAVI between 2011 and 2017 were allocated to two matched groups depending whether the procedure was performed before or after transition from standard to fast track course. Data on vital status and hospitalizations were obtained through national registries. Three hundred and nineteen matched pairs were eligible for analysis. The median length of post-procedural stay was 3 days (IQR: 2-4) for patients in the fast track group compared to 6 days (IQR: 4-8) in the standard approach group (p < .0001). There was no difference in all-cause mortality between groups at 30-day (1.3% vs. 1.9%, p = .52) or 90-day follow-up (2.9% vs. 4.1%, p = .42). There was no difference in the risk of new permanent pacemaker implantation (PPI) in pacemaker naïve patients between groups at 30-day (15.8% vs. 21.2%, p = .16) or 90-day follow-up (15.8% vs. 21.9%, p = .12). There was no difference in the rate of rehospitalization between groups between discharge and 90-day follow-up (2.09 per patient-year vs. 2.09 per patient-year, p = .99). CONCLUSIONS: Early discharge in an all-comers population undergoing transfemoral TAVI is safe with regards to all-cause mortality, need for PPI, and rehospitalization.

The effect of transcatheter aortic valve implantation approaches on mortality.

OBJECTIVES: We aimed to evaluate the effect of transcatheter aortic valve implantation (TAVI) approaches on mortality and identify effect modifiers and predictors for mortality. BACKGROUND: Alternative access routes to transfemoral (TF) TAVI include the surgical intra-thoracic direct-aortic (DA) and transapical (TA) approach. TA TAVI has been associated with a higher mortality rate. We hypothesized that this is related to effect modifiers, in particular the left ventricular ejection fraction (LVEF). METHODS: This multicentre study derived its data from prospective registries. To adjust for confounders, we used propensity-score based, stabilized inverse probability weighted Cox regression models. RESULTS: In total, 5,910 patients underwent TAVI via TF (N = 4,072), DA (N = 524), and TA (N = 1,314) access. Compared to TF, 30-day mortality was increased among DA (HR 1.87, 95%CI 1.26-2.78, p = .002) and TA (HR 3.34, 95%CI 2.28-4.89, p < .001) cases. Compared to TF, 5-year mortality was increased among TA cases (HR 1.50, 95%CI 1.24-1.83, p < .001). None of the variables showed a significant interaction between the approaches and mortality. An impaired LVEF (≤35%) increased mortality in all approaches. CONCLUSIONS: The surgical intra-thoracic TA and DA TAVI are both associated with a higher 30-day mortality than TF TAVI. TA TAVI is associated with a higher 5-year mortality than TF TAVI. The DA approach may therefore have some advantages over the TA approach when TF access is not feasible.

Clinical impact of conduction disturbances in transcatheter aortic valve replacement recipients: a systematic review and meta-analysis.

AIMS: The clinical impact of new-onset persistent left bundle branch block (NOP-LBBB) and permanent pacemaker implantation (PPI) on transcatheter aortic valve replacement (TAVR) recipients remains controversial. We aimed to evaluate the impact of (i) periprocedural NOP-LBBB and PPI post-TAVR on 1-year all-cause death, cardiac death, and heart failure hospitalization and (ii) NOP-LBBB on the need for PPI at 1-year follow-up. METHODS AND RESULTS: We performed a systematic search from PubMed and EMBASE databases for studies reporting raw data on 1-year clinical impact of NOP-LBBB or periprocedural PPI post-TAVR. Data from 30 studies, including 7792 patients (12 studies) and 42 927 patients (21 studies) for the evaluation of the impact of NOP-LBBB and PPI after TAVR were sourced, respectively. NOP-LBBB was associated with an increased risk of all-cause death [risk ratio (RR) 1.32, 95% confidence interval (CI) 1.17-1.49; P < 0.001], cardiac death (RR 1.46, 95% CI 1.20-1.78; P < 0.001), heart failure hospitalization (RR 1.35, 95% CI 1.05-1.72; P = 0.02), and PPI (RR 1.89, 95% CI 1.58-2.27; P < 0.001) at 1-year follow-up. Periprocedural PPI after TAVR was associated with a higher risk of all-cause death (RR 1.17, 95% CI 1.11-1.25; P < 0.001) and heart failure hospitalization (RR 1.18, 95% CI 1.03-1.36; P = 0.02). Permanent pacemaker implantation was not associated with an increased risk of cardiac death (RR 0.84, 95% CI 0.67-1.05; P = 0.13). CONCLUSION: NOP-LBBB and PPI after TAVR are associated with an increased risk of all-cause death and heart failure hospitalization at 1-year follow-up. Periprocedural NOP-LBBB also increased the risk of cardiac death and PPI within the year following the procedure. Further studies are urgently warranted to enhance preventive measures and optimize the management of conduction disturbances post-TAVR.

Five-Year Clinical and Echocardiographic Outcomes From the NOTION Randomized Clinical Trial in Patients at Lower Surgical Risk.

BACKGROUND: The NOTION trial (Nordic Aortic Valve Intervention) was designed to compare transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) in patients ≥70 years old with isolated severe aortic valve stenosis. Clinical and echocardiographic outcomes are presented after 5 years. METHODS: Patients were enrolled at 3 Nordic centers and randomized 1:1 to TAVR using the self-expanding CoreValve prosthesis (n=145) or SAVR using any stented bioprostheses (n=135). The primary composite outcome was the rate of all-cause mortality, stroke, or myocardial infarction at 1 year defined according to Valve Academic Research Consortium-2 criteria. RESULTS: Baseline characteristics were similar. The mean age was 79.1±4.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 3.0%±1.7%. After 5 years, there were no differences between TAVR and SAVR in the composite outcome (Kaplan-Meier estimates 38.0% versus 36.3%, log-rank test P=0.86) or any of its components. TAVR patients had larger prosthetic valve area (1.7 cm2 versus 1.2 cm2, P<0.001) with a lower mean transprosthetic gradient (8.2 mm Hg versus 13.7 mm Hg, P<0.001), both unchanged over time. More TAVR patients had moderate/severe total aortic regurgitation (8.2% versus 0.0%, P<0.001) and a new pacemaker (43.7% versus 8.7%, P<0.001). Four patients had prosthetic reintervention and no difference was found for functional outcomes. CONCLUSIONS: These are currently the longest follow-up data comparing TAVR and SAVR in lower risk patients, demonstrating no statistical difference for major clinical outcomes 5 years after TAVR with a self-expanding prosthesis compared to SAVR. Higher rates of prosthetic regurgitation and pacemaker implantation were seen after TAVR. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01057173.

Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study.

BACKGROUND: Subclinical leaflet thrombosis of bioprosthetic aortic valves after transcatheter valve replacement (TAVR) and surgical aortic valve replacement (SAVR) has been found with CT imaging. The objective of this study was to report the prevalence of subclinical leaflet thrombosis in surgical and transcatheter aortic valves and the effect of novel oral anticoagulants (NOACs) on the subclinical leaflet thrombosis and subsequent valve haemodynamics and clinical outcomes on the basis of two registries of patients who had CT imaging done after TAVR or SAVR. METHODS: Patients enrolled between Dec 22, 2014, and Jan 18, 2017, in the RESOLVE registry, and between June 2, 2014, and Sept 28, 2016, in the SAVORY registry, had CT imaging done with a dedicated four-dimensional volume-rendered imaging protocol at varying intervals after TAVR and SAVR. We defined subclinical leaflet thrombosis as the presence of reduced leaflet motion, along with corresponding hypoattenuating lesions shown with CT. We collected data for baseline demographics, antithrombotic therapy, and clinical outcomes. We analysed all CT scans, echocardiograms, and neurological events in a masked fashion. FINDINGS: Of the 931 patients who had CT imaging done (657 [71%] in the RESOLVE registry and 274 [29%] in the SAVORY registry), 890 [96%] had interpretable CT scans (626 [70%] in the RESOLVE registry and 264 [30%] in the SAVORY registry). 106 (12%) of 890 patients had subclinical leaflet thrombosis, including five (4%) of 138 with thrombosis of surgical valves versus 101 (13%) of 752 with thrombosis of transcatheter valves (p=0·001). The median time from aortic valve replacement to CT for the entire cohort was 83 days (IQR 33-281). Subclinical leaflet thrombosis was less frequent among patients receiving anticoagulants (eight [4%] of 224) than among those receiving dual antiplatelet therapy (31 [15%] of 208; p<0·0001); NOACs were equally as effective as warfarin (three [3%] of 107 vs five [4%] of 117; p=0·72). Subclinical leaflet thrombosis resolved in 36 (100%) of 36 patients (warfarin 24 [67%]; NOACs 12 [33%]) receiving anticoagulants, whereas it persisted in 20 (91%) of 22 patients not receiving anticoagulants (p<0·0001). A greater proportion of patients with subclinical leaflet thrombosis had aortic valve gradients of more than 20 mm Hg and increases in aortic valve gradients of more than 10 mm Hg (12 [14%] of 88) than did those with normal leaflet motion (seven [1%] of 632; p<0·0001). Although stroke rates were not different between those with (4·12 strokes per 100 person-years) or without (1·92 strokes per 100 person-years) reduced leaflet motion (p=0·10), subclinical leaflet thrombosis was associated with increased rates of transient ischaemic attacks (TIAs; 4·18 TIAs per 100 person-years vs 0·60 TIAs per 100 person-years; p=0·0005) and all strokes or TIAs (7·85 vs 2·36 per 100 person-years; p=0·001). INTERPRETATION: Subclinical leaflet thrombosis occurred frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. Anticoagulation (both NOACs and warfarin), but not dual antiplatelet therapy, was effective in prevention or treatment of subclinical leaflet thrombosis. Subclinical leaflet thrombosis was associated with increased rates of TIAs and strokes or TIAs. Despite excellent outcomes after TAVR with the new-generation valves, prevention and treatment of subclinical leaflet thrombosis might offer a potential opportunity for further improvement in valve haemodynamics and clinical outcomes. FUNDING: RESOLVE (Cedars-Sinai Heart Institute) and SAVORY (Rigshospitalet).

Recurrence of new-onset post-operative AF after cardiac surgery: detected by implantable loop recorders: A systematic review and Meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. New-onset post-operative AF may signal an elevated risk of AF and associated outcomes in long-term follow-up. We aimed to estimate the rate of AF recurrence as detected by an implantable loop recorder (ILR) in patients experiencing post-operative AF within 30 days after cardiac surgery. METHODS: We searched MEDLINE, Embase and Cochrane CENTRAL to April 2023 for studies of adults who did not have known AF, experienced new-onset AF within 30 days of cardiac surgery and received an ILR. We pooled individual participant data on timing of AF recurrence using a random-effects model with a frailty model applied to a Cox proportional hazard analysis. RESULTS: From 8671 citations, 8 single-centre prospective cohort studies met eligibility criteria. Data were available from 185 participants in 7 studies, with a median follow-up of 1.7 (IQR: 1.3-2.8) years. All included studies were at a low risk of bias. Pooled AF recurrence rates following 30 post-operative days were 17.8% (95% CI 11.9%-23.2%) at 3 months, 24.4% (17.7%-30.6%) at 6 months, 30.1% (22.8%-36.7%) at 12 months and 35.3% (27.6%-42.2%) at 18 months. CONCLUSIONS: In patients who experience new-onset post-operative AF after cardiac surgery, AF recurrence lasting at least 30 s occurs in approximately 1 in 3 in the first year after surgery. The optimal frequency and modality to use for monitoring for AF recurrence in this population remain uncertain.

Determinants of adverse outcomes following patent foramen ovale closure in elderly patients.

BACKGROUND: Limited data are available on transcatheter patent foramen ovale (PFO) closure outcomes in the elderly. AIMS: Through this study, we aimed to determine the incidence and predictors of adverse events (recurrent cerebrovascular events [CVE] and atrial fibrillation [AF]) post-PFO closure in older patients with cryptogenic events. METHODS: This multicentre international study included patients over 60 years undergoing PFO closure for cryptogenic thromboembolic events. A dedicated database compiled baseline, procedural, and follow-up data. Competing risk and adjusted outcome predictor analyses were conducted. RESULTS: A total of 689 patients were included (median age 65 years, 41.2% female, mean Risk of Paradoxical Embolism [RoPE] score 4.5). The procedural success rate was 99.4%. After a median follow-up of 2 (interquartile range 1-5) years, 66 patients (9.6%) had died. CVE and stroke rates were 1.21 and 0.55 per 100 patient-years, respectively. Diabetes (hazard ratio [HR] 3.89, 95% confidence interval [CI]: 1.67-9.07; p=0.002) and atrial septal aneurysm (ASA; HR 5.25, 95% CI: 1.56-17.62; p=0.007) increased the CVE risk. New-onset AF occurred at a rate of 3.30 per 100 patient-years, with 51.3% within one month post-procedure. Older age (HR 1.05 per year, 95% CI: 1.00-1.09; p=0.023) and the absence of hypertension (HR 2.04, 95% CI: 1.19-3.57; p=0.010) were associated with an increased risk of AF. CONCLUSIONS: Older patients undergoing PFO closure had a relatively low rate of CVE and new-onset AF after a median follow-up of 2 years. The presence of diabetes, ASA, and a more advanced age determined an increased risk of adverse clinical events. These factors may be considered in the clinical decision-making process regarding PFO closure in this challenging population.

Pulmonary Valve Replacement in Tetralogy of Fallot: Procedural Volume and Durability of Bioprosthetic Pulmonary Valves.

BACKGROUND: Robust data on changes in pulmonary valve replacement (PVR) procedural volume and predictors of bioprosthetic pulmonary valve (BPV) durability in patients with tetralogy of Fallot (TOF) are scarce. OBJECTIVES: This study sought to assess temporal trends in PVR procedural volume and BPV durability in a nationwide, retrospective TOF cohort. METHODS: Data were obtained from patient records. Robust linear regression was used to assess temporal trends in PVR procedural volume. Piecewise exponential additive mixed models were used to estimate BPV durability, defined as the time from implantation to redo PVR with death as a competing risk, and to assess risk factors for reduced durability. RESULTS: In total, 546 PVR were performed in 384 patients from 1976 to 2021. The annual number of PVR increased from 0.4 to 6.0 per million population (P < 0.001). In the last decade, the transcatheter PVR volume increased by 20% annually (P < 0.001), whereas the surgical PVR volume did not change significantly. The median BPV durability was 17 years (Q1: 10-Q3: 10 years-not applicable). There was no significant difference in the durability of different BPV after adjustment for confounders. Age at PVR (HR: 0.78 per 10 years from <1 year; 95% CI: 0.63-0.96; P = 0.02) and true inner valve diameter (9-17 mm vs 18-22 mm HR: 0.40; 95% CI: 0.22-0.73; P = 0.003 and 18-22 mm vs 23-30 mm HR: 0.59; 95% CI: 0.25-1.39; P = 0.23) were associated with reduced BPV durability in multivariate models. CONCLUSIONS: The PVR procedural volume has increased over time, with a greater increment in transcatheter than surgical PVR during the last decade. Younger patient age at PVR and a smaller true inner valve diameter predicted reduced BPV durability.

Association between organic dietary choice during pregnancy and hypospadias in offspring: a study of mothers of 306 boys operated on for hypospadias.

PURPOSE: The etiology of hypospadias is poorly understood. Exposure to pesticides has been considered a risk factor, although findings are inconsistent. Diet constitutes a significant exposure route for pesticides, and pesticide residues are more frequently reported in conventional than organic food products. We examined the association between organic dietary choice during pregnancy and presence of hypospadias in the offspring. MATERIALS AND METHODS: Mothers of 306 boys operated on for hypospadias were frequency matched for geography and child birth year to 306 mothers of healthy boys in a case-control study. Telephone interviews were conducted regarding demographic and lifestyle factors, including intake and organic choice of selected food items (milk, dairy products, egg, fruit, vegetables and meat). Logistic regression models were constructed for dietary variables, and odds ratios were calculated controlling for maternal age, body mass index and alcohol consumption. RESULTS: Overall organic choice of food items during pregnancy was not associated with hypospadias in the offspring. However, frequent current consumption of high fat dairy products (milk, butter) while rarely or never choosing the organic alternative to these products during pregnancy was associated with increased odds of hypospadias (adjusted OR 2.18, 95% CI 1.09-4.36). CONCLUSIONS: This large case-control study of boys operated on for hypospadias suggests an association between hypospadias in the offspring and the mother not choosing the organic alternative, and having a high current intake of nonorganic butter and cheese. This finding could be due to chemical contamination of high fat dairy products. However, general lifestyle and health behavior related to choosing organic alternatives may also explain the finding.

Comparison of middle-term valve durability between transcatheter aortic valve implantation and surgical aortic valve replacement: an updated systematic review and meta-analysis of RCTs.

Background: This study aims to compare valve durability between transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). Methods: We conducted a systematic review and meta-analysis using data from randomized controlled trials (RCTs). The primary outcome was structural valve deterioration (SVD). Secondary outcomes were bioprosthetic valve failure, reintervention, effective orifice area (EOA), mean pressure gradient, and moderate-severe aortic regurgitation (AR, transvalvular and/or paravalvular). Results: Twenty-five publications from seven RCTs consisting of 7,970 patients were included in the analysis with follow-up ranges of 2-8 years. No significant difference was found between the two groups with regard to SVD [odds ratio (OR) 0.72; 95% CI: 0.25-2.12]. The TAVI group was reported to exhibit a statistically significant higher risk of reintervention (OR 2.03; 95% CI: 1.34-3.05) and a moderate-severe AR (OR 6.54; 95% CI: 3.92-10.91) compared with the SAVR group. A trend toward lower mean pressure gradient in the TAVI group [(mean difference (MD) -1.61; 95% CI: -3.5 to 0.28)] and significant higher EOA (MD 0.20; 95% CI: 0.08-0.31) was noted. Conclusion: The present data indicate that TAVI provides a comparable risk of SVD with favorable hemodynamic profile compared with SAVR. However, the higher risk of significant AR and reintervention was demonstrated. Systematic Review Registration: PROSPERO (CRD42022363060).

Incidence, predictors, and prognostic impact of rehospitalization after transcatheter aortic valve implantation.

AIMS: Despite rehospitalization being common after transcatheter aortic valve implantation (TAVI), an in-depth analysis on this topic is missing. This study sought to report on the incidence, predictors, and prognostic impact of rehospitalization within one year following TAVI. METHODS AND RESULTS: All consecutive patients treated with TAVI between 2016 and 2020 in East Denmark were included. Medical records of all patients were reviewed to validate rehospitalizations up to 1 year after discharge from the index admission. The study population consisted of 1,397 patients, of whom 615 (44%) had an unplanned rehospitalization within the first year post-TAVI. The rehospitalization incidence rate was 3-fold higher in the early period (within 30 days) compared with the late period (30 days to 1 year; 2.5 vs. 0.8 per patient-year, respectively; p < 0.001). Predictors of early unplanned rehospitalization were procedure-related complications and prior stroke, whereas late unplanned rehospitalization was associated with pre-existing comorbidities. Predictors of HF rehospitalization included ischemic heart disease, the extent of cardiac damage, atrial fibrillation, and NYHA class at baseline. HF rehospitalization within 30 days and 1-year post-TAVI was associated with a markedly increased 1-year and 5-year mortality risk (hazard ratio (HR) of 4.3 and 3.2 for 1-year mortality and HR of 3.2 and 2.9 for 5-year mortality, respectively; p < 0.001). CONCLUSIONS: Rehospitalization after TAVI is frequent in real-world practice. Early rehospitalization is mostly procedure-related whereas late rehospitalization is related to pre-existing comorbidities. HF rehospitalization is associated with poor long-term survival and could be validated as a prognostically relevant endpoint for TAVI trials.