ABSTRACT
AIMS: Guidelines recommend opportunistic screening for atrial fibrillation (AF), using a 30â s single-lead electrocardiogram (ECG) recorded by a wearable device. Since many patients have paroxysmal AF, identification of patients at high risk presenting with sinus rhythm (SR) may increase the yield of subsequent long-term cardiac monitoring. The aim is to evaluate an AI-algorithm trained on 10â s single-lead ECG with or without risk factors to predict AF. METHODS AND RESULTS: This retrospective study used 13 479 ECGs from AF patients in SR around the time of diagnosis and 53 916 age- and sex-matched control ECGs, augmented with 17 risk factors extracted from electronic health records. AI models were trained and compared using 1- or 12-lead ECGs, with or without risk factors. Model bias was evaluated by age- and sex-stratification of results. Random forest models identified the most relevant risk factors. The single-lead model achieved an area under the curve of 0.74, which increased to 0.76 by adding six risk factors (95% confidence interval: 0.74-0.79). This model matched the performance of a 12-lead model. Results are stable for both sexes, over ages ranging from 40 to 90 years. Out of 17 clinical variables, 6 were sufficient for optimal accuracy of the model: hypertension, heart failure, valvular disease, history of myocardial infarction, age, and sex. CONCLUSION: An AI model using a single-lead SR ECG and six risk factors can identify patients with concurrent AF with similar accuracy as a 12-lead ECG-AI model. An age- and sex-matched data set leads to an unbiased model with consistent predictions across age groups.
Subject(s)
Atrial Fibrillation , Male , Female , Humans , Atrial Fibrillation/diagnosis , Artificial Intelligence , Retrospective Studies , Electrocardiography/methods , Risk FactorsABSTRACT
Background: The presence of a chronic total occlusion (CTO) and severe left ventricular (LV) systolic dysfunction are known negative prognostic factors in patients with coronary artery disease. Several studies have examined the effect of CTO revascularization on mortality, symptoms, occurrence of myocardial infarction (MI), and cardiac function in patients with normal or reduced LV function. However, the effect of CTO revascularization on heart failure-related events in patients with LV dysfunction, such as heart failure hospitalization (HFH), the occurrence of atrial fibrillation (AF), and a worsening renal function (WRF), has not yet been evaluated. To assess the success rate and safety of CTO percutaneous coronary interventions (PCIs) in coronary patients with LV ejection fractions of ≤ 40% and evaluate the impact of successful CTO revascularization on HFH, occurrence of AF, and WRF. Methods: Prospectively, data were collected from CTO PCIs performed at three referral centers and analyzed. From a total of 1435 CTO PCIs, 132 (9.2%) patients with a left ventricular ejection fraction (LVEF) of ≤ 40% were included in this analysis. The median follow-up duration was 23.18 months (interquartile range (IQR): 11.02-46.66 months). Results: A successful CTO PCI was achieved in 109 of these patients, while the procedure was unsuccessful in 23 patients (82.5% procedural success rate). Overall, the intervention had an acceptable number of peri-procedural (or in-hospital) complications (9.1%). During the follow-up period, the rates of all-cause death, cardiovascular death, and non-fatal MI were not significantly different between the two groups. The rates of HFH were significantly lower in the successful PCI group, while WRF and AF did not differ between successful and unsuccessful PCI groups. Successful PCI and higher estimated glomerular filtration rate (eGFR) were independent predictors of a lower risk of HFH, while prior stroke and diabetes were independent predictors of a higher risk of HFH. Conclusions: In patients with reduced LV systolic function (ejection fraction, EF ≤ 40%), CTO PCI is a safe and effective procedure and successful CTO PCI is independently associated with a lower risk of HFH during follow-up. Further expansion of this cohort is necessary to confirm these results.
ABSTRACT
OBJECTIVES: This study aimed to assess the rate of difficult interatrial septum (IAS) crossing with the intracardiac echocardiography (ICE) probe during percutaneous left atrial appendage (LAA) closure and to identify techniques that facilitate IAS crossing with the ICE probe. BACKGROUND: Percutaneous LAA closure is increasingly performed by ICE guidance. Although such an approach omits the need for general anesthesia, crossing of the IAS with the ICE probe may sometimes be challenging. METHODS: All consecutive patients that underwent ICE-guided percutaneous LAA closure with an Amplatzer Amulet (Abbott) or WatchmanFLX (Boston Scientific) at our center in the period 2018-2021 were included. Cases in which IAS crossing with ICE was difficult were identified and techniques used to facilitate IAS crossing were identified and listed. RESULTS: In 17 (5%) out of 354 cases, IAS crossing with the ICE probe was difficult and required use of additional techniques. Ultimately, IAS crossing was also successful in these 17 cases by using one of three possible facilitation techniques: the probing technique (12 cases), the double-wire technique (3 cases), and the snaring technique (2 cases). In one case, the double-wire technique was converted to the snaring technique, as crossing of the ICE probe remained challenging despite the use of two stiff guidewires. CONCLUSION: Crossing of the IAS with the ICE probe can be challenging in 5% of ICE-guided percutaneous LAA closure procedures. Operators should be aware of possible facilitation techniques in challenging cases, as these show to be safe and effective.
Subject(s)
Atrial Appendage , Atrial Fibrillation , Humans , Atrial Appendage/diagnostic imaging , Echocardiography, Transesophageal , Cardiac Catheterization/adverse effects , Cardiac Catheterization/methods , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/therapy , Ultrasonography, Interventional/methods , Treatment OutcomeABSTRACT
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.
ABSTRACT
Bioprosthetic surgical aortic valve failure requiring reintervention is a frequent clinical problem with event rates up to 20% at 10 years after surgery. Transcatheter aortic valve-in-valve implantation (ViV-TAVI) has become a valuable treatment option for these patients, although it requires careful procedural planning. We here describe and illustrate a stepwise approach to plan and perform ViV-TAVI and discuss preprocedural computerized tomography planning, transcatheter heart valve selection, and implantation techniques. Particular attention is paid to coronary artery protection and the possible need for bioprosthetic valve fracture since patients with small surgical aortic bioprostheses are at a risk of high residual gradients after ViV-TAVI. Considering updated clinical data on long-term outcomes following ViV-TAVI, this approach may become the default treatment strategy for patients with a failing surgical aortic bioprosthesis.
Subject(s)
Aortic Valve Stenosis , Bioprosthesis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Bioprosthesis/adverse effects , Heart Valve Prosthesis/adverse effects , Heart Valve Prosthesis Implantation/methods , Humans , Prosthesis Design , Prosthesis Failure , Surgical Instruments , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Treatment OutcomeABSTRACT
BACKGROUND: Oral bleeding after dental extraction in patients on non-vitamin K oral anticoagulants (NOACs) is a frequent problem. We investigated whether 10% tranexamic acid (TXA) mouthwash decreases post-extraction bleeding in patients treated with NOACs. METHODS AND FINDINGS: The EXTRACT-NOAC study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial. Patients were randomly assigned to 10% TXA or placebo mouthwash and were instructed to use the mouthwash once prior to dental extraction, and thereafter for 3 times a day for 3 days. The primary outcome was the number of patients with any post-extraction oral bleeding up to day 7. Secondary outcomes included periprocedural, early, and delayed bleeding, and the safety outcomes included all thrombotic events. The first patient was randomized on February 9, 2018 and the last patient on March 12, 2020. Of 222 randomized patients, 218 patients were included in the full analysis set, of which 106 patients were assigned to TXA (74.8 (±8.8) years; 81 men) and 112 to placebo (72.7 (±10.7) years; 64 men). Post-extraction bleeding occurred in 28 (26.4%) patients in the TXA group and in 32 (28.6%) patients in the placebo group (relative risk, 0.92; 95% confidence interval [CI], 0.60 to 1.42; P = 0.72). There were 46 bleeds in the TXA group and 85 bleeds in the placebo group (rate ratio, 0.57; 95% CI, 0.31 to 1.05; P = 0.07). TXA did not reduce the rate of periprocedural bleeding (bleeding score 4 ± 1.78 versus 4 ± 1.82, P = 0.80) and early bleeding (rate ratio, 0.76; 95% CI, 0.42 to 1.37). Delayed bleeding (rate ratio, 0.32; 95% CI, 0.12 to 0.89) and bleeding after multiple extractions (rate ratio, 0.40; 95% CI, 0.20 to 0.78) were lower in the TXA group. One patient in the placebo group had a transient ischemic attack while interrupting the NOAC therapy in preparation for the dental extraction. Two of the study limitations were the premature interruption of the trial following a futility analysis and the assessment of the patients' compliance that was based on self-reported information during follow-up. CONCLUSIONS: In patients on NOACs undergoing dental extraction, TXA does not seem to reduce the rate of periprocedural or early postoperative oral bleeding compared to placebo. TXA appears to reduce delayed bleeds and postoperative oral bleeding if multiple teeth are extracted. TRIAL REGISTRATION: ClinicalTrials.gov NCT03413891 EudraCT; EudraCT number:2017-001426-17; EudraCT Public website: eudract.ema.europa.eu.
Subject(s)
Anticoagulants/administration & dosage , Antifibrinolytic Agents/therapeutic use , Hemorrhage/prevention & control , Postoperative Hemorrhage/drug therapy , Tooth Extraction/adverse effects , Tranexamic Acid/therapeutic use , Administration, Oral , Aged , Aged, 80 and over , Belgium , Double-Blind Method , Female , Humans , Male , Middle Aged , Postoperative Hemorrhage/etiology , Prospective StudiesABSTRACT
Although concomitant coronary artery disease (CAD) is frequent in patients with severe aortic stenosis (AS), hemodynamic assessment of CAD severity in patients undergoing valve replacement for severe AS is challenging. Myocardial hypertrophic remodeling interferes with coronary blood flow and may influence the values of fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). The aim of the current study is to investigate the effect of the AS and its treatment on current indices used for evaluation of CAD. We will compare intracoronary hemodynamics before, immediately after, and 6 mo after aortic valve replacement (AVR) when it is expected that microvascular function has improved. Furthermore, we will compare FFR and resting full-cycle ratio (RFR) with myocardial perfusion single-photon emission-computed tomography (SPECT) as indicators of myocardial ischemia in patients with AS and CAD. One-hundred consecutive patients with AS and intermediate CAD will be prospectively included. Patients will undergo pre-AVR SPECT and intracoronary hemodynamic assessment at baseline, immediately after valve replacement [if transcatheter AVR (TAVR) is chosen], and 6 mo after AVR. The primary end point is the change in FFR 6 mo after AVR. Secondary end points include the acute change of FFR after TAVR, the diagnostic accuracy of FFR versus RFR compared with SPECT for the assessment of ischemia, changes in microvascular function as assessed by the index of microcirculatory resistance (IMR), and the effect of these changes on FFR. The present study will evaluate intracoronary hemodynamic parameters before, immediately after, and 6 mo after AVR in patients with AS and intermediate coronary stenosis. The understanding of the impact of AVR on the assessment of FFR, NHPR, and microvascular function may help guide the need for revascularization in patients with AS and CAD planned for AVR.
Subject(s)
Aortic Valve Stenosis/diagnostic imaging , Aortic Valve/diagnostic imaging , Coronary Artery Disease/diagnostic imaging , Coronary Circulation , Hemodynamics , Microcirculation , Myocardial Perfusion Imaging , Research Design , Tomography, Emission-Computed, Single-Photon , Aortic Valve/physiopathology , Aortic Valve/surgery , Aortic Valve Stenosis/complications , Aortic Valve Stenosis/physiopathology , Aortic Valve Stenosis/surgery , Belgium , Clinical Decision-Making , Coronary Artery Disease/complications , Coronary Artery Disease/physiopathology , Coronary Artery Disease/surgery , Fractional Flow Reserve, Myocardial , Humans , Predictive Value of Tests , Prospective Studies , Severity of Illness Index , Time Factors , Transcatheter Aortic Valve Replacement , Treatment OutcomeABSTRACT
We have previously demonstrated that systemic AMP-activated protein kinase α1 (AMPKα1) invalidation enhanced adverse LV remodelling by increasing fibroblast proliferation, while myodifferentiation and scar maturation were impaired. We thus hypothesised that fibroblastic AMPKα1 was a key signalling element in regulating fibrosis in the infarcted myocardium and an attractive target for therapeutic intervention. The present study investigates the effects of myofibroblast (MF)-specific deletion of AMPKα1 on left ventricular (LV) adaptation following myocardial infarction (MI), and the underlying molecular mechanisms. MF-restricted AMPKα1 conditional knockout (cKO) mice were subjected to permanent ligation of the left anterior descending coronary artery. cKO hearts exhibit exacerbated post-MI adverse LV remodelling and are characterised by exaggerated fibrotic response, compared to wild-type (WT) hearts. Cardiac fibroblast proliferation and MF content significantly increase in cKO infarcted hearts, coincident with a significant reduction of connexin 43 (Cx43) expression in MFs. Mechanistically, AMPKα1 influences Cx43 expression by both a transcriptional and a post-transcriptional mechanism involving miR-125b-5p. Collectively, our data demonstrate that MF-AMPKα1 functions as a master regulator of cardiac fibrosis and remodelling and might constitute a novel potential target for pharmacological anti-fibrotic applications.
Subject(s)
AMP-Activated Protein Kinases/deficiency , Connexin 43/metabolism , Myocardial Infarction/enzymology , Myocardium/enzymology , Myofibroblasts/enzymology , Ventricular Function, Left , Ventricular Remodeling , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Animals , Cell Proliferation , Connexin 43/genetics , Disease Models, Animal , Female , Fibrosis , Gene Deletion , HEK293 Cells , Humans , Male , Mice, Knockout , MicroRNAs/genetics , MicroRNAs/metabolism , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardium/pathology , Myofibroblasts/pathology , Signal TransductionABSTRACT
BACKGROUND: The MAVIG X-ray protective drape (MXPD) has been shown to reduce operator radiation dose during percutaneous coronary interventions (PCI). Whether MXPDs are also effective in reducing operator radiation during chronic total occlusion (CTO) PCI, often with dual access, is unknown. METHODS: We performed a prospective, randomized-controlled study comparing operator radiation dose during CTO PCI (n = 60) with or without pelvic MXPDs. The primary outcomes were the difference in first operator radiation dose (µSv) and relative dose of the first operator (radiation dose normalized for dose area product) at the level of the chest in the two groups. The effectiveness of MXPD in CTO PCI was compared with non-CTO PCI using a patient-level pooled analysis with a previously published non-CTO PCI randomized study. RESULTS: The use of the MXPD was associated with a 37% reduction in operator dose (weighted median dose 26.0 (IQR 10.00-29.47) µSv in the drape group versus 41.8 (IQR 30.82-60.59) µSv in the no drape group; P < 0.001) and a 60% reduction in relative operator dose (median dose 3.5 (IQR 2.5-5.4) E/DAPx10-3 in the drape group versus 8.6 (IQR 4.2-12.5) E/DAPx10-3 in the no drape group; P=0.001). MXPD was equally effective in reducing operator dose in CTO PCI compared with non-CTO PCI (P value for interaction 0.963). CONCLUSIONS: The pelvic MAVIG X-ray protective drape significantly reduced CTO operator radiation dose. This trial is clinically registered with https://www.clinicaltrials.gov (unique identifier: NCT04285944).
Subject(s)
Coronary Occlusion , Occupational Exposure , Percutaneous Coronary Intervention , Chronic Disease , Coronary Angiography , Coronary Occlusion/surgery , Humans , Occupational Exposure/adverse effects , Percutaneous Coronary Intervention/adverse effects , Prospective Studies , Radiation Dosage , Risk Factors , Treatment Outcome , X-RaysABSTRACT
BACKGROUND: The field of CTO PCI is expanding, but successful and safe percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTO) requires a substantial resource and experience investment. We aimed to assess temporal trends in strategies and outcomes of 2 dedicated programs for CTO PCI. METHODS: Between 2011 and 2020, 920 CTO PCI procedures were prospectively included at 2 referral centres in Belgium. Temporal trends were assessed, and logistic regression models were built to identify predictors of outcome. RESULTS: Despite an increase in lesion complexity (the J-CTO score increased from 1.3 in year 1 to 1.7-2.0 in years 8-9, p < 0.001), technical success improved from 70.0% to 85.6% in year 9 (p value for trend <0.001). We observed the most significant improvement starting at years 3-4 (OR 2.3 in year 4 versus year 1, p=0.018). Together with an increase in success rates and lesions complexity, there was an increase in the use of dual injections, retrograde approaches, the number of balloons and stents, and the use of microcatheters. Conversely, there was a decrease in large bore access, an increase in radial approach, and a shift towards contemporary dissection/reentry techniques. This strategy resulted in a stable major complication rate of 4.7% (p value for trend 0.33). The rate of coronary procedure-related myocardial injury was high (71.0%) and was associated with the use of more intracoronary devices. CONCLUSIONS: Three to four years after initiation of a dedicated CTO PCI program with 50 CTO PCIs per year, consistent high technical success and low complication rates are achieved using contemporary strategies.
Subject(s)
Coronary Occlusion , Percutaneous Coronary Intervention , Chronic Disease , Coronary Angiography , Coronary Occlusion/surgery , Humans , Prospective Studies , Registries , Risk Factors , Treatment OutcomeABSTRACT
AIMS: During the first 6-12 h of intensive care unit (ICU) stay, post-cardiac arrest (CA) patients treated with a mean arterial pressure (MAP) 65 mmHg target experience a drop of the cerebral oxygenation that may cause additional cerebral damage. Therefore, we investigated whether an early goal directed haemodynamic optimization strategy (EGDHO) (MAP 85-100 mmHg, SVO2 65-75%) is safe and could improve cerebral oxygenation, reduce anoxic brain damage, and improve outcome when compared with a MAP 65 mmHg strategy. METHODS AND RESULTS: A total of 112 out-of-hospital CA patients were randomly assigned to EGDHO or MAP 65 mmHg strategies during the first 36 h of ICU stay. The primary outcome was the extent of anoxic brain damage as quantified by the percentage of voxels below an apparent diffusion coefficient (ADC) score of 650.10-6 mm2/s on diffusion weighted magnetic resonance imaging (at day 5 ± 2 post-CA). Main secondary outcome was favourable neurological outcome (CPC score 1-2) at 180 days. In patients assigned to EGDHO, MAP (P < 0.001), and cerebral oxygenation during the first 12 h of ICU stay (P = 0.04) were higher. However, the percentage of voxels below an ADC score of 650.10-6 mm2/s did not differ between both groups [16% vs. 12%, odds ratio 1.37, 95% confidence interval (CI) 0.95-0.98; P = 0.09]. Also, the number of patients with favourable neurological outcome at 180 days was similar (40% vs. 38%, odds ratio 0.98, 95% CI 0.41-2.33; P = 0.96). The number of serious adverse events was lower in patients assigned to EGDHO (P = 0.02). CONCLUSION: Targeting a higher MAP in post-CA patients was safe and improved cerebral oxygenation but did not improve the extent of anoxic brain damage or neurological outcome.
Subject(s)
Hemodynamics/physiology , Hypoxia, Brain/prevention & control , Neuroprotection/physiology , Out-of-Hospital Cardiac Arrest/therapy , Aged , Brain/blood supply , Brain/diagnostic imaging , Brain/pathology , Coma/etiology , Coma/physiopathology , Diffusion Magnetic Resonance Imaging , Female , Humans , Hypoxia, Brain/etiology , Male , Middle Aged , Out-of-Hospital Cardiac Arrest/complications , Oxygen/blood , Oxygen/metabolism , Treatment Outcome , Troponin/bloodABSTRACT
OBJECTIVE: The interruption of antithrombotics prior to tooth removal because of the fear of bleeding or following postoperative bleeding increases the risk of thromboembolic events. The aim of this systematic review was to investigate which local haemostatic measures can effectively prevent postoperative bleeding in patients continuing oral antithrombotics. METHODS: A systematic review was conducted by running a search in PubMed, Embase, Web of Science and Cochrane Library. Clinical randomised trials investigating bleeding and haemostatics after tooth removal in patients on antithrombotics were identified. RESULTS: In total, 15 articles were included. The investigated haemostatics included gauze pressure, tranexamic acid-soaked gauze, sponges, glue, calcium sulfate, plant extract Ankaferd Blood Stopper, epsilon-aminocaproic acid and tranexamic acid. In patients treated with vitamin K antagonists, tranexamic acid mouthwash significantly reduced bleeding compared to placebo. Further, histoacryl glue was proven better than gelatin sponges. Other studies failed to show significant differences between haemostatics, but bleeding events were low. CONCLUSIONS: Tranexamic acid seems to effectively reduce bleeding, although its superiority to other haemostatics was not proven. In view of the rapidly changing landscape of antithrombotics and the lack of standardization of bleeding outcome, adequately powered clinical studies are required to optimise postoperative management in patients on antithrombotics. CLINICAL RELEVANCE: In order to optimise postoperative management, the best haemostatics over different patient groups have to be identified and implemented in guidelines.
Subject(s)
Antifibrinolytic Agents , Fibrinolytic Agents , Hemostatics , Tooth Extraction , Antifibrinolytic Agents/therapeutic use , Fibrinolytic Agents/therapeutic use , Hemostatics/therapeutic use , Humans , Tranexamic AcidABSTRACT
Optimal healing after myocardial infarction requires not only the induction of inflammation, but also its timely resolution. In patients, 30 days post myocardial infarction, circulating monocytes have increased expression of Semaphorin3A (Sema3A) as compared to directly after admission. This increased expression coincides with increased expression of Cx3CR1-a marker of non-classical monocytes that are important for immune resolution hence proper wound healing. In mice, the expression of Sema3A also increases in response to myocardial ischemia being expressed by infiltrating leukocytes. Comparing Sema3A heterozygote (HZ) and wild type (WT) mice post myocardial infarction, revealed increased presence of leukocytes in the cardiac tissues of HZ mice as compared to WT, with no differences in capillary density, collagen deposition, cardiomyocyte surface area, chemokine-or adhesion molecules expression. Whilst infarct sizes were similar 14 days after myocardial infarction in both genotypes, Sema3A HZ mice had thinner infarcts and reduced cardiac function as compared to their WT littermates. In vitro experiments were conducted to study the role of Sema3A in inflammation and resolution of inflammation as a potential explanation for the differences in leukocyte recruitment and cardiac function observed in our in vivo experiments. Here, recombinant Sema3A protein was able to affect the pro-inflammatory state of cultured bone marrow derived macrophages. First, the pro-inflammatory state was altered by the induced apoptosis of classical macrophages in the presence of Sema3A. Second, Sema3A promoted the polarization of classical macrophages to resolution-phase macrophages and enhanced their efferocytotic ability, findings that were reflected in the infarcted cardiac tissue of the Sema3A HZ mice. Finally, we demonstrated that besides promoting resolution of inflammation, Sema3A was also able to retard the migration of monocytes to the myocardium. Collectively our data demonstrate that Sema3A reduces cardiac inflammation and improves cardiac function after myocardial infarction by promoting the resolution of inflammation.
Subject(s)
Myocardial Infarction/metabolism , Myocarditis/metabolism , Myocardium/metabolism , Semaphorin-3A/metabolism , Wound Healing , Animals , Apoptosis , Cells, Cultured , Chemotaxis, Leukocyte , Disease Models, Animal , Female , Heterozygote , Macrophage Activation , Macrophages/metabolism , Macrophages/pathology , Male , Mice, Knockout , Monocytes/metabolism , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocarditis/genetics , Myocarditis/pathology , Myocarditis/physiopathology , Myocardium/pathology , Phenotype , Recovery of Function , Semaphorin-3A/deficiency , Semaphorin-3A/genetics , Signal Transduction , Time FactorsABSTRACT
Extracellular vesicles are now widely recognized as key players in the prevention, repair or progression of cardiovascular disease. Here we first focus on the functional roles of extracellular vesicles in the cross-talk between cardiomyocytes and endothelial cells, important for maintaining normal development and function of the heart. Second, we discuss the role of extracellular vesicles secreted by embryonic and non-embryonic stem cells in repairing cardiomyocyte function and in restoring angiogenic potential after myocardial ischemia-reperfusion injury. Third, we focus on the role of extracellular vesicles in Endothelial to Mesenchymal Transition (EndMT), leading to conversion of endothelial cells to fibroblasts, secretion of extracellular proteins collagen and fibronectin, and fibrosis. Finally, we discuss the role of extracellular vesicles secreted under stress by endothelial cells, macrophages and vascular smooth muscle cells in atherosclerosis. On aggregate, the reviewed preclinical studies present evidence that extracellular vesicles secreted by cardiomyocytes, fibroblasts, endothelial cells, immune-system-related cells, vascular smooth muscle cells and stem cells play an important role in the pathogenesis of cardiovascular disease. However, further studies are needed to gain better insight into the mechanisms used to select specific content to transfer to specific target cells, and to induce or repress signaling pathways in their target cells.
Subject(s)
Coronary Artery Disease/metabolism , Coronary Vessels/metabolism , Exosomes/metabolism , Heart Diseases/metabolism , Myocardium/metabolism , Signal Transduction , Animals , Cell Communication , Coronary Artery Disease/pathology , Coronary Vessels/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Epithelial-Mesenchymal Transition , Exosomes/pathology , Heart Diseases/pathology , Humans , Myocardium/pathology , Plaque, Atherosclerotic , Stem Cells/metabolism , Stem Cells/pathologyABSTRACT
OBJECTIVES: The aim of this study was to validate a standardized pragmatic approach to manage new oral anticoagulants (NOACs) in patients who undergo dental extractions. MATERIALS AND METHODS: This prospective case-control study in patients undergoing dental extraction included 26 patients (mean age 76 years, 57% male) treated with dabigatran, rivaroxaban, or apixaban and 26 matched controls. Regardless of timing of extraction, drug regimen, or renal function, patients were instructed to skip only the dose on the morning of the procedure. A procedural bleeding score was recorded and early and delayed bleeding was assessed at day 1 and day 7. Bleeding events were compared with a prospectively matched control group not taking any antithrombotic drug. RESULTS: There was no difference in the procedural bleeding score or in early bleeding events (5 in both groups). However, delayed bleeding occurred more frequently in anticoagulated compared to non-anticoagulated patients (7 versus none, p = 0.01). CONCLUSIONS: Skipping the morning dose of NOACs avoids excess bleeding during and early after the procedure. However, anticoagulated patients had an increased risk of delayed bleedings. Further study is needed to determine the optimal post-procedural management. CLINICAL RELEVANCE: This is the first prospective study for the management of patients on NOACs undergoing dental extraction. Our pragmatic approach, omitting only a single morning dose, can guide clinical practice. Both patients and physicians should be aware of the increased delayed bleeding risk.
Subject(s)
Anticoagulants/administration & dosage , Dental Care for Chronically Ill , Oral Hemorrhage/prevention & control , Tooth Extraction , Administration, Oral , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Male , Prospective StudiesSubject(s)
Fibrinolytic Agents/administration & dosage , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction/therapy , Shock, Cardiogenic/prevention & control , Thrombolytic Therapy , Drug Administration Schedule , Fibrinolytic Agents/adverse effects , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Randomized Controlled Trials as Topic , Risk Factors , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/physiopathology , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/mortality , Shock, Cardiogenic/physiopathology , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Time Factors , Time-to-Treatment , Treatment OutcomeABSTRACT
BACKGROUND: The obesity-related hormones leptin and adiponectin are independently and oppositely associated with insulin resistance, which is an important risk factor for coronary artery disease (CAD) and restenosis after coronary intervention. In this report, we set out to determine the role of the leptin-adiponectin ratio (LAR) in non-diabetic patients with or without impaired glucose tolerance undergoing a percutaneous coronary intervention. METHODS: 300 PCI patients were enrolled in this prospective single-centre study. Patients with known diagnosis of diabetes (n = 50) and newly diagnosed diabetes (2h OGTT > 200 mg/dL, n = 25) were excluded. In both stable and acute subjects, assessment was done on the day of discharge and included a fasting glucose level, leptin, adiponectin and an oral glucose tolerance test (OGTT). RESULTS: LAR was significantly higher in diabetic (7.2 ± 0.7) than in non-diabetic patients (3.9 ± 0.3, P = 0.001), and even higher in newly diagnosed diabetics (9.8 ± 1.5, P < 0.001). Likewise, among non-diabetic patients, LAR was significantly higher in patients with impaired glucose tolerance. LAR was significantly higher in pre-diabetic (4.57 ± 0.48) versus normoglycaemic patients (3.45 ± 0.33, P = 0.05). LAR was found to be numerically higher in pre-diabetic versus normoglycaemic patients with two- and three-vessel disease (VD), but not in patients with single VD. In pre-diabetic patients, LAR was found to be significantly increased with more advanced CAD (P = 0.021), independent of stable versus unstable presentation. CONCLUSIONS: LAR is related to the extent of CAD in pre-diabetic patients but not in normoglycaemic patients. This finding might in part explain the poorer outcome in revascularized patients with impaired glucose tolerance compared to normoglycaemic patients.
Subject(s)
Adiponectin/blood , Coronary Artery Disease/blood , Leptin/blood , Percutaneous Coronary Intervention , Prediabetic State/blood , Aged , Biomarkers/blood , Blood Glucose/metabolism , Coronary Angiography , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prediabetic State/complications , Preoperative Period , Prospective Studies , Risk FactorsABSTRACT
BACKGROUND: Both surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) are Class Ia recommended therapies for specific subgroups of severe aortic stenosis (AS) patients in the latest 2021 European guidelines. AIMS: We aimed to report on the multidisciplinary Heart Team evaluation process and real-world practice of treating severe symptomatic AS in East Denmark in the context of the latest European guideline recommendations. METHODS: All consecutive patients with severe AS referred for intervention in 2021 (N=672) were discussed in a multidisciplinary Heart Team meeting. All patients (100%) had a cardiac computed tomography (CT) analysis prior to the meeting. Baseline characteristics, Heart Team decision-making, final treatment and 30-day clinical outcomes were prospectively recorded. RESULTS: The majority of severe AS patients (N=456, 68%) were referred for TAVI following discussion in the Heart Team. Ultimately, 94% of patients (N=632) received the Heart Team-recommended treatment. Patients undergoing TAVI (N=439) were significantly older (78.4±6.7 vs 67.2±8.3 years; p<0.001) and more comorbid than patients undergoing SAVR (N=189). The overall 30-day clinical outcomes were satisfactory for both treatment groups (overall 30-day mortality: 1.1%). The mean index hospitalisation length was markedly longer in the SAVR group (8.6±8.3 days) as compared to the TAVI group (1.8±3.2 days). CONCLUSIONS: TAVI was routinely performed in low surgical risk patients in 2021 with two-thirds of all severe AS patients undergoing TAVI, thereby applying the latest European guidelines. A dedicated Heart Team meeting, including CT evaluation for all AS patients, is needed to make individualised management decisions in this new era of aortic valve interventions.
Subject(s)
Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Humans , Heart , Hospitalization , Patients , Aortic Valve Stenosis/surgeryABSTRACT
BACKGROUND: The percutaneous treatment of calcified coronary lesions remains challenging and is associated with worse clinical outcomes. In addition, coronary artery calcification is associated with more frequent peri-procedural myocardial infarction. STUDY DESIGN AND OBJECTIVES: The ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions (SONAR) study is an investigator-initiated, prospective, randomized, international, multicenter, open label trial (NCT05208749) comparing a lesion preparation strategy with either shockwave intravascular lithotripsy (IVL) or rotational atherectomy (RA) before drug-eluting stent implantation in 170 patients with moderate to severe calcified coronary lesions. The primary endpoint is difference in the rate of peri-procedural myocardial infarction. Key secondary endpoints include rate of peri-procedural microvascular dysfunction, peri-procedural myocardial injury, descriptive study of IMR measurements in calcified lesions, technical and procedural success, interaction between OCT calcium score and primary endpoint, 30-day and 1-year major adverse clinical events. CONCLUSIONS: The SONAR trial is the first randomized controlled trial comparing the incidence of peri-procedural myocardial infarction between 2 contemporary calcium modification strategies (Shockwave IVL and RA) in patients with calcified coronary artery lesions. Furthermore, for the first time, the incidence of peri-procedural microvascular dysfunction after Shockwave IVL and RA will be evaluated and compared.
Subject(s)
Atherectomy, Coronary , Coronary Artery Disease , Drug-Eluting Stents , Myocardial Infarction , Percutaneous Coronary Intervention , Vascular Calcification , Humans , Atherectomy, Coronary/adverse effects , Prospective Studies , Coronary Vessels/diagnostic imaging , Coronary Vessels/surgery , Calcium , Coronary Angiography , Treatment Outcome , Vascular Calcification/diagnostic imaging , Vascular Calcification/therapy , Vascular Calcification/etiology , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/etiology , Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effects , AtherectomyABSTRACT
AIM: Transcatheter aortic valve implantation (TAVI) is a mainstay in the management of severe aortic valve stenosis in elderly patients, but there is uncertainty on their long-term effectiveness. We aimed to assess the long-term outcome of patients undergoing TAVI with the Portico valve. METHODS: We retrospectively collected the data on patients in whom TAVI with Portico was attempted from 7 high-volume centres. Only patients theoretically eligible for 3 or more years of follow-up were included. Clinical outcomes, including death, stroke, myocardial infarction, reintervention for valve degeneration and hemodynamic valve performance were systematically assessed. RESULTS: A total of 803 patients were included, with 504 (62.8%) women, mean age of 82 years, median EuroSCORE II of 3.1%, and 386 (48.1%) subjects at low/moderate risk. The median follow-up was 3.0 years (3.0; 4.0). The composite of death, stroke, myocardial infarction, and reintervention for valve degeneration occurred in 37.5% (95% confidence interval: 34.1-40.9%), with all-cause death in 35.1% (31.8-38.4%), stroke in 3.4% (1.3-3.4%), myocardial infarction in 1.0% (0.3-1.5%), and reintervention for valve degeneration in 1.1% (0.6-2.1%). The mean aortic valve gradient at follow-up was 8.1 ± 4.6 mmHg, and at least moderate aortic regurgitation was present in 9.1% (6.7-12.3%). Independent predictors of major adverse events or death were: peripheral artery disease, chronic obstructive pulmonary disease, estimated glomerular filtration rate, atrial fibrillation, prior pacemaker implantation, EuroSCORE II, and reduced left ventricular ejection fraction (all p < 0.05). CONCLUSIONS: Portico use is associated with favorable long-term clinical outcomes. Clinical outcomes were largely impacted by baseline risk factors and surgical risk.