Prediction of the Individual Aortic Stenosis Progression Rate and its Association With Clinical Outcomes.

Background: The progression rate of aortic stenosis differs between patients, complicating clinical follow-up and management. Objectives: This study aimed to identify predictors associated with the progression rate of aortic stenosis. Methods: In this retrospective longitudinal single-center cohort study, all patients with moderate aortic stenosis who presented between December 2011 and December 2022 and had echocardiograms available were included. The individual aortic stenosis progression rate was calculated based on aortic valve area (AVA) from at least 2 echocardiograms performed at least 6 months apart. Baseline factors associated with the progression rate of AVA were determined using linear mixed-effects models, and the association of progression rate with clinical outcomes was evaluated using Cox regression. Results: The study included 540 patients (median age 69 years and 38% female) with 2,937 echocardiograms (median 5 per patient). Patients had a linear progression with a median AVA decrease of 0.09 cm2/y and a median peak jet velocity increase of 0.17 m/s/y. Rapid progression was independently associated with all-cause mortality (HR: 1.77, 95% CI: 1.26-2.48) and aortic valve replacement (HR: 3.44, 95% CI: 2.55-4.64). Older age, greater left ventricular mass index, atrial fibrillation, and chronic kidney disease were associated with a faster decline of AVA. Conclusions: AVA decreases linearly in individual patients, and faster progression is independently associated with higher mortality. Routine clinical and echocardiographic variables accurately predict the individual progression rate and may aid clinicians in determining the optimal follow-up interval for patients with aortic stenosis.

Sex Differences in Outcomes After Transcatheter Aortic Valve Replacement: A POPular TAVI Subanalysis.

BACKGROUND: Stroke and bleeding are complications after transcatheter aortic valve replacement (TAVR). A higher incidence of bleeding and stroke has been reported in women, but the role of antithrombotic management pre- and post-TAVR has not been studied. OBJECTIVES: The study sought to compare bleeding and ischemic complications after TAVR between women and men stratified by antiplatelet and oral anticoagulant (OAC) regimen. METHODS: The POPular TAVI (Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation) trial was a randomized clinical trial to test the hypothesis that monotherapy with aspirin or OAC after TAVR is safer than the addition of clopidogrel. The primary endpoints of interest of this post hoc subanalysis were: 1) all bleeding; and 2) a composite of ischemic events consisting of stroke and myocardial infarction. Secondary endpoints were: 1) nonprocedural bleeding; 2) major or life-threatening bleeding; 3) minor bleeding; 4) stroke; 5) myocardial infarction; and 6) all-cause death. RESULTS: A total of 978 patients (466 [47.6%] women) were included in this study. All bleeding and the composite of myocardial infarction and stroke rates were similar between sexes (all bleeding: 106 [22.8%] women vs 121 [23.6%] men; P = 0.815; ischemic events: 26 [5.6%] vs 36 [7.0%]; P = 0.429). However, major or life-threatening bleeding occurred more often in women (58 [12.5%]) vs men (38 [7.4%]) (P = 0.011), most of which were access site bleedings. The use of aspirin pre- and post-TAVR increased major or life-threatening bleeding in women but not in men. CONCLUSIONS: After TAVR, overall bleeding and ischemic outcomes were similar between women and men. However, women had more major or life-threatening bleedings, especially those receiving aspirin pre- and post-TAVR.

Transcatheter edge-to-edge repair of tricuspid regurgitation in the Netherlands: state of the art and future perspectives.

Despite the high prevalence and adverse clinical outcomes of severe tricuspid regurgitation (TR), conventional treatment options, surgical or pharmacological, are limited. Surgery is associated with a high peri-operative risk and medical treatment has not clearly resulted in clinical improvements. Therefore, there is a high unmet need to reduce morbidity and mortality in patients with severe TR. During recent years, several transcatheter solutions have been studied. This review focuses on the transcatheter edge-to-edge repair of TR (TTVR) with respect to patient selection, the procedure, pre- and peri-procedural echocardiographic assessments and clinical outcomes. Furthermore, we highlight the current status of TTVR in the Netherlands and provide data from our initial experience at the University Medical Centre Groningen.

Computational quantitative flow ratio to assess functional severity of coronary artery stenosis.

Background Computational quantitative flow ratio (QFR) based on 3-dimensional quantitative coronary angiography (3D QCA) analysis offers the opportunity to assess the significance of coronary artery disease (CAD) without using an invasive pressure wire or inducing hyperemia. This study aimed to evaluate the diagnostic performance of QFR compared to wire-based fractional flow reserve (FFR) and to validate the previously reported QFR cut-off value of >0.90 to safely rule out functionally significant CAD. Methods QFR was retrospectively derived from standard-care coronary angiograms. Correlation and agreement of fixed-flow QFR (fQFR) and contrast-flow QFR (cQFR) models with invasive wire-based FFR was calculated. Diagnostic performance of QFR was evaluated at different QFR cut-off values defining significant CAD (FFR ≤ 0.80). Results 101 vessels in 96 patients who underwent FFR were studied. Mean FFR was 0.87 ±â€¯0.08 and 21 of 101 (21%) vessels had an FFR ≤ 0.80. Correlation of fQFR and cQFR with FFR was r = 0.71 (p < 0.001) and r = 0.70 (p < 0.001), respectively. Sensitivity and specificity were 57% and 93% for fQFR and 67% and 96% for cQFR at a QFR cut-off value >0.80 defining non-significant CAD, respectively. fQFR > 0.90 was present in 34 (34%) and cQFR > 0.90 in 39 (39%) vessels. For both QFR models, none of the vessels with QFR > 0.90 had an FFR ≤ 0.80. Conclusions QFR appears to be a safe and effective gatekeeper to wire-based FFR when applying a QFR threshold of >0.90 to rule out significant CAD. Further prospective research is required to establish QFR in the real-life setting of functional CAD assessment in the catheterization laboratory.

Left ventricular restoration devices post myocardial infarction.

Even in the era of percutaneous reperfusion therapy, left ventricular (LV) remodeling after myocardial infarction (MI) leading to heart failure remains a major health concern. Contractile dysfunction of the infarcted myocardium results in an increased pressure load, leading to maladaptive reshaping of the LV. Several percutaneous transcatheter procedures have been developed to deliver devices that restore LV shape and function. The purposes of this review are to discuss the spectrum of transcatheter devices that are available or in development for attenuation of adverse LV remodeling and to critically examine the available evidence for improvement of functional status and cardiovascular outcomes.

In vivo coronary lesion differentiation with computed tomography angiography and intravascular ultrasound as compared to optical coherence tomography.

BACKGROUND: In vitro studies have shown the feasibility of coronary lesion grading with computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as compared to histology, whereas OCT had the highest discriminatory capacity. OBJECTIVE: We investigated the ability of CTA and IVUS to differentiate between early and advanced coronary lesions in vivo, OCT serving as standard of reference. METHODS: Multimodality imaging was prospectively performed in 30 NSTEMI patients. Plaque characteristics were assessed in 1083 cross-sections of 30 culprit lesions, co-registered among modalities. Absence of plaque, fibrous and fibrocalcific plaque on OCT were defined as early plaque, whereas lipid rich-plaque on OCT was defined as advanced plaque. Odds ratios adjusted for clustering were calculated to assess associations between plaque types on CTA and IVUS with early or advanced plaque. RESULTS: Normal findings on CTA as well as on IVUS were associated with early plaque. Non-calcified, calcified plaques and the napkin ring sign on CTA were associated with advanced plaque. On IVUS, fatty and calcified plaques were associated with advanced plaque. CONCLUSIONS: In vivo coronary plaque characteristics on CTA and IVUS are associated with plaque characteristics on OCT. Of note, normal findings on CTA and IVUS relate to early lesions on OCT. Nevertheless, multiple plaque features on CTA and IVUS are related to advanced plaques on OCT, which may make it difficult to use qualitative plaque assessment in clinical practice.

Filter-based cerebral embolic protection with transcatheter aortic valve implantation: the randomised MISTRAL-C trial.

AIMS: Our aim was to determine whether use of the filter-based Sentinel™ Cerebral Protection System (CPS) during transcatheter aortic valve implantation (TAVI) can affect the early incidence of new brain lesions, as assessed by diffusion-weighted magnetic resonance imaging (DW-MRI), and neurocognitive performance. METHODS AND RESULTS: From January 2013 to July 2015, 65 patients were randomised 1:1 to transfemoral TAVI with or without the Sentinel CPS. Patients underwent DW-MRI and extensive neurological examination, including neurocognitive testing one day before and five to seven days after TAVI. Follow-up DW-MRI and neurocognitive testing was completed in 57% and 80%, respectively. New brain lesions were found in 78% of patients with follow-up MRI. Patients with the Sentinel CPS had numerically fewer new lesions and a smaller total lesion volume (95 mm3 [IQR 10-257] vs. 197 mm3 [95-525]). Overall, 27% of Sentinel CPS patients and 13% of control patients had no new lesions. Ten or more new brain lesions were found only in the control cohort (in 20% vs. 0% in the Sentinel CPS cohort, p=0.03). Neurocognitive deterioration was present in 4% of patients with Sentinel CPS vs. 27% of patients without (p=0.017). The filters captured debris in all patients with Sentinel CPS protection. CONCLUSIONS: Filter-based embolic protection captures debris en route to the brain in all patients undergoing TAVI. This study suggests that its use can lead to fewer and overall smaller new brain lesions, as assessed by MRI, and preservation of neurocognitive performance early after TAVI. CLINICAL TRIAL REGISTRATION: Dutch trial register-ID: NTR4236. URL http://www.trialregister.nl/trialreg/admin/rctsearch.asp?Term=mistral.

Rationale and design of POPular-TAVI: antiPlatelet therapy fOr Patients undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Despite improving experience and techniques, ischemic and bleeding complications after transcatheter aortic valve implantation (TAVI) remain prevalent and impair survival. Current guidelines recommend the temporary addition of clopidogrel in the initial period after TAVI to prevent thromboembolic events. However, explorative studies suggest that this is associated with a higher rate of major bleeding without a decrease in thromboembolic complications. METHODS: The POPular TAVI trial is a prospective randomized, controlled, open-label multicenter clinical trial to test the hypothesis that monotherapy with aspirin or oral anticoagulation (OAC) after TAVI is safer than the addition of clopidogrel for 3 months, without compromising clinical benefit. This trial encompasses 2 cohorts: cohort A, patients are randomized 1:1 to aspirin vs aspirin + clopidogrel, and cohort B, patients on OAC therapy are randomized 1:1 to OAC vs OAC + clopidogrel. Primary outcome is freedom from non-procedure-related bleeding at 1 year. Secondary net-clinical benefit outcome is freedom from the composite of cardiovascular death, non-procedural-related bleeding, myocardial infarction, or stroke at 1 year. The primary outcome is analyzed for superiority, whereas the secondary outcome is analyzed for noninferiority. Recruitment began in February 2014, and the trial will continue until a total of 1,000 patients (684 expected in cohort A and 316 in cohort B) are included and followed up for 1 year. SUMMARY: The POPular TAVI trial (NCT02247128) is the first large randomized controlled trial to test if monotherapy with aspirin or OAC vs additional clopidogrel after TAVI reduces bleeding with a favorable net-clinical benefit.

Soluble interleukin 6 receptor levels are associated with reduced myocardial reperfusion after percutaneous coronary intervention for acute myocardial infarction.

AIMS: Interleukin-6 receptor (IL-6R) signalling has been suggested to play a causal role in the development and outcome of coronary heart disease (CHD). The aim of this study was to investigate the association of sIL-6R levels with myocardial reperfusion after percutaneous coronary intervention (PCI) for acute ST-elevated myocardial infarction (STEMI). METHODS: Blood was sampled from 70 patients presenting with STEMI at 6 different time-points (baseline, post-PCI, t=1h, t=6h, t=24h, t=2w). Coronary angiograms post-PCI were analysed for myocardial blush grade (MBG) as indicator of myocardial reperfusion. Serum IL-6 and sIL-6R were measured using IL-6 and sIL-6R enzyme-linked immunosorbent assays (ELISA). RESULTS: sIL-6R levels fluctuated biphasic during the two weeks after STEMI. Reduced MBG was associated with a larger change in sIL-6R levels between baseline and post-PCI compared to optimal MBG (-13.40; SEM 2.78ng/ml vs -1.99; SEM 2.35ng/ml, respectively; p<0.001). Patients with reduced MBG also showed a larger increase in sIL-6R levels after PCI and 1h after myocardial infarction (MI) compared to optimal MBG (respectively 11.56; SEM 2.68ng/ml vs 3.02; SEM 2.39ng/ml; p=0.018). IL-6/sIL-6R ratio was also more increased in patients with reduced MBG at 24h after myocardial infarction (0.23; SEM 0.08-0.51 vs 0.10; SEM 0.05-0.21; p=0.024). An optimal MBG was associated with a 10ng increase in sIL-6R level between baseline and post-PCI (OR 1.687, CI 1.095-2.598; p=0.018). CONCLUSIONS: sIL-6R levels fluctuate biphasic during the two weeks after MI with larger changes and increased IL-6/sIL-6R ratio in patients with reduced MBG. Further research is needed to increase our understanding of the possible causality of these associations.

Repositioning of an intraventricular dislocated aortic valve during transcatheter aortic valve implantation.

The case is presented of a 75-year-old man referred for transcatheter aortic valve implantation. During the procedure the prosthetic aortic valve became dislocated into the left ventricle shortly after expansion. The subsequent steps taken to reposition the valve using only materials at hand are described.

Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.

IMPORTANCE: Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function. OBJECTIVE: To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI). DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013. INTERVENTIONS: Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure. RESULTS: At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed. CONCLUSIONS AND RELEVANCE: Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01217307.

Percutaneous aortic valve replacement using a subclavian artery graft.

Over the past few years transcatheter heart valve implantation (THI) has become an alternative treatment for aortic valve replacement. The THI does not require a midline sternotomy or cardiopulmonary bypass and can be performed through a transfemoral or a transapical approach. In case of severe peripheral vascular disease the transapical route is usually chosen. However, when the use of a small anterolateral thoracotomy is not preferred due to comorbidities, the subclavian artery can be considered as a third alternative route. This case report describes an approach for THI through the subclavian artery, by using a Dacron graft.

Percutaneous Edwards SAPIEN valve implantation in the tricuspid position: case report and review of literature.

AIMS: Experience with transcatheter valve-in-valve implantation in a failing bioprosthetic tricuspid valve is very limited. Fewer than 30 cases have been reported, and in most of them the Melody valve (Medtronic, Inc., Minneapolis, MN, USA) was used. With this case report and review of literature we sought to evaluate the safety and feasibility of the Edwards SAPIEN transcatheter valve (Edwards Lifesciences, Irvine, CA, USA) in valve implantation in the tricuspid position and to compare this intervention with the more established Melody valve implantation. METHODS AND RESULTS: We describe one of the rarely reported Edwards SAPIEN valve implantations in a bioprosthetic tricuspid valve which is also the first in a patient with Ebstein's anomaly. A review is presented of all eight case reports on Edwards SAPIEN valve implantations in tricuspid position. The procedure was successful in all cases. Valve performance after implantation was good and no complications were described. In only one procedure pre-stenting was performed. Transatrial, transjugular and transfemoral approaches have been used. The results are comparable to those of the series about Melody valve-in-valve implantation in the tricuspid valve. Mid-term follow-up data are not yet available for both valves. CONCLUSIONS: Edwards SAPIEN valve implantation in tricuspid bioprosthetic valves is feasible and safe. Considering the available sizes of the Edwards SAPIEN valve, it may become the preferred prosthesis for valve-in-valve implantation in the tricuspid position in the future.

Usefulness of thrombus aspiration for the treatment of coronary stent thrombosis.

Current treatment for coronary stent thrombosis (ST) often lacks satisfactory results and clinical outcome is poor. We investigated the impact of manual thrombus aspiration during percutaneous coronary intervention (PCI) on myocardial reperfusion and clinical outcome in patients with angiographically proved ST. We interrogated our PCI registry for patients with a first stent placement from January 2002 through May 2010 who had undergone an emergency repeated PCI procedure and systematically reviewed coronary angiograms and hospital records for evidence of ST. We identified 113 patients with ST. Thrombus aspiration was used in 51 patients and 62 patients received conventional PCI. Histopathologic analysis of thrombus aspirates was performed in 6 patients. Use of thrombus aspiration predicted postprocedure Thrombolysis In Myocardial Infarction grade 3 flow (odds ratio 3.16, 95% confidence interval 1.22 to 8.17, p = 0.018) and myocardial blush grade 2/3 (odds ratio 3.20, 95% confidence interval 1.20 to 8.55, p = 0.020) after multivariable adjustment with bootstrap model selection. Distal embolization was lower in the thrombus aspiration group compared to the conventional PCI group (14% vs 37%, p = 0.017). In most patients, aspirated thrombus was large and contained platelet and erythrocyte components at histopathologic analysis. Mortality in the thrombus aspiration group and conventional PCI group was 9.8% versus 16% at 30 days (p = 0.351) and 12% versus 21% at 1 year (p = 0.220), respectively. In conclusion, use of manual thrombus aspiration in patients with ST was associated with greater epicardial and microvascular myocardial reperfusion. In addition, mortality was lower in patients treated with thrombus aspiration, although not statistically significant.

Comparison of the temporal release pattern of copeptin with conventional biomarkers in acute myocardial infarction.

BACKGROUND: Early detection of acute myocardial infarction (AMI) using cardiac biomarkers of myocardial necrosis remains limited since these biomarkers do not rise within the first hours from onset of AMI. We aimed to compare the temporal release pattern of the C-terminal portion of provasopressin (copeptin) with conventional cardiac biomarkers, including creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnT), and high-sensitivity cTnT (hs-cTnT), in patients with ST-elevation AMI. METHODS: We included 145 patients undergoing successful primary percutaneous coronary intervention (PCI) for a first ST-elevation AMI presenting within 12 h of symptom onset. Blood samples were taken on admission and at four time points within the first 24 h after PCI. RESULTS: In contrast to all other markers, copeptin levels were already elevated on admission and were higher with a shorter time from symptom onset to reperfusion and lower systolic blood pressure. Copeptin levels peaked immediately after symptom onset at a maximum of 249 pmol/L and normalized within 10 h. In contrast, CK-MB, cTnT, and hs-cTnT peaked after 14 h from symptom onset at a maximum of 275 U/L, 5.75 µg/L, and 4.16 µg/L, respectively, and decreased more gradually. CONCLUSIONS: Copeptin has a distinct release pattern in patients with ST-elevation AMI, peaking within the first hour after symptom onset before conventional cardiac biomarkers and falling to normal ranges within the first day. Further studies are required to determine the exact role of copeptin in AMI suspects presenting within the first hours after symptom onset.

Operator dependence of outcome after primary percutaneous coronary intervention.

AIMS: Primary percutaneous coronary intervention (PCI) is a widely practised therapeutic procedure to treat ST-elevation myocardial infarction (STEMI). However, a significant proportion of patients undergoing primary PCI suffers from adverse events, such as incomplete myocardial reperfusion. It is currently unknown to which degree these adverse events are operator related. METHODS AND RESULTS: We investigated inter-operator variation using objective safety and efficacy endpoints during primary PCI for STEMI. All PCIs were performed by six experienced interventional cardiologists as part of a randomised single centre trial. The primary endpoint of this study was optimal myocardial reperfusion (myocardial blush grade 3 [MBG]). All 1,071 patients enrolled in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) were included in this analysis. In the six operator groups, the rate of the primary endpoint MBG 3 ranged between 29.2% and 55.5%. The variable for operators remained significantly associated with MBG 3 after adjustment for baseline and procedural differences. There were no statistical differences observed with regard to safety endpoints. CONCLUSIONS: This study illustrates the observation that even in a controlled setting significant inter-operator variation may exist in the efficacy of primary PCI. This study supports the routine collection of high-quality datasets to evaluate and improve individual operator competence and skills.

Intracoronary versus intravenous administration of abciximab in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration: the comparison of intracoronary versus intravenous abciximab administration during emergency reperfusion of ST-segment elevation myocardial infarction (CICERO) trial.

BACKGROUND: administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary over intravenous administration of abciximab, this has not been investigated in a medium-scale randomized clinical trial. METHODS AND RESULTS: a total of 534 ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration within 12 hours of symptom onset were randomized to either an intracoronary or an intravenous bolus of abciximab (0.25 mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel. The primary end point was the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution. Secondary end points included myocardial reperfusion as assessed by myocardial blush grade, enzymatic infarct size, and major adverse cardiac events at 30 days. The incidence of complete ST-segment resolution was similar in the intracoronary and intravenous groups (64% versus 62%; P=0.562). However, the incidence of myocardial blush grade 2/3 was higher in the intracoronary group than in the intravenous group (76% versus 67%; P=0.022). Furthermore, enzymatic infarct size was smaller in the intracoronary than in the intravenous group (P=0.008). The incidence of major adverse cardiac events was similar in both groups (5.5% versus 6.1%; P=0.786). CONCLUSIONS: in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with thrombus aspiration, intracoronary administration of abciximab compared with intravenous administration does not improve myocardial reperfusion as assessed by ST-segment resolution. However, intracoronary administration is associated with improved myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size.