Platelets and Cardiac Arrhythmia

Sudden cardiac death (SCD) remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g., serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic-acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium, and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products

Improving the efficiency of the cardiac catheterization laboratories through understanding the stochastic behavior of the scheduled procedures

  Background: In this study, we sought to analyze the stochastic behavior of Catherization Labora­tories (Cath Labs) procedures in our institution. Statistical models may help to improve estimated case durations to support management in the cost-effective use of expensive surgical resources. Methods: We retrospectively analyzed all the procedures performed in the Cath Labs in 2012. The duration of procedures is strictly positive (larger than zero) and has mostly a large mini­mum duration. Because of the strictly positive character of the Cath Lab procedures, a fit of a lognormal model may be desirable. Having a minimum duration requires an estimate of the threshold (shift) parameter of the lognormal model. Therefore, the 3-parameter lognormal model is interesting. To avoid heterogeneous groups of observations, we tested every group-car­diologist-procedure combination for the normal, 2- and 3-parameter lognormal distribution. Results: The total number of elective and emergency procedures performed was 6,393 (8,186 h). The final analysis included 6,135 procedures (7,779 h). Electrophysiology (intervention) pro­cedures fit the 3-parameter lognormal model 86.1% (80.1%). Using Friedman test statistics, we conclude that the 3-parameter lognormal model is superior to the 2-parameter lognormal model. Furthermore, the 2-parameter lognormal is superior to the normal model. Conclusions: Cath Lab procedures are well-modelled by lognormal models. This information helps to improve and to refine Cath Lab schedules and hence their efficient use.

Arrhythmia mechanism dependent pulmonary vein ablation in paroxysmal atrial fibrillation

Atrial fibrillation (AF) often requires invasive treatment by ablation to decrease symptom burden. The pulmonary veins (PV) are thought to trigger paroxysms of AF, and ablative PV isolation (PVI) is a cornerstone in AF treatment. However, incomplete PVI, where electrical conduction between the PV and left atrium (LA) is maintained, is curative of AF in a subset of patients. This implies that an antiarrhythmic effect other than electrical isolation between the PV and LA plays a role in AF prevention in these patients. We reason that the PV myocardium constitutes an arrhythmogenic substrate conducive to reentry in the patients with curative incomplete PVI. This PV substrate is amenable to ablation, even when conduction between the LA and PV persists. We propose that PV ablation strategies are differentiated to fit the arrhythmogenic mechanisms in the individual patient. PV substrate modification in patients with PV reentry may constitute a new therapeutic approach that is potentially simpler and more effective, in this subgroup of patients

Low rate of asymptomatic cerebral embolism and improved procedural efficiency with the novel pulmonary vein ablation catheter GOLD: results of the PRECISION GOLD trial

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Careful Curation of Care Content:A Case Study of a Technology-Supported Atrial Fibrillation Outpatient Clinic

Medical care received outside the doctor’s office and the hospital is gaining traction. Lifestyle programs for transmural and remote care are increasingly facilitated by hospitals as part of rehabilitation, by general practitioners as preventative measures, and by various private (health) organizations through consumer apps. What is often overlooked is the time and energy spent on creating the content (i.e., health information and education) in these programs so that it is effective, appealing, relatable, and personalized. In this article, we discuss the elaborate content creation process of lifestyle content for an outpatient clinic for atrial fibrillation patients. We describe the close collaboration between clinicians, design researchers, data designers, and a copywriter, and reflect on how to streamline and formalize the clinical content creation process. Additionally, we highlight opportunities for further content personalization by making it dynamic, more versatile in terms of delivery and expanding the system further into the home context

Prehospital risk assessment in patients suspected of non-ST-segment elevation acute coronary syndrome:a systematic review and meta-analysis

OBJECTIVE: To review, inventory and compare available diagnostic tools and investigate which tool has the best performance for prehospital risk assessment in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: Systematic review and meta-analysis. Medline and Embase were searched up till 1 April 2021. Prospective studies with patients, suspected of NSTE-ACS, presenting in the primary care setting or by emergency medical services (EMS) were included. The most important exclusion criteria were studies including only patients with ST-elevation myocardial infarction and studies before 1995, the pretroponin era. The primary end point was the final hospital discharge diagnosis of NSTE-ACS or major adverse cardiac events (MACE) within 6 weeks. Risk of bias was evaluated by the Quality Assessment of Diagnostic Accuracy Studies Criteria. MAIN OUTCOME AND MEASURES: Sensitivity, specificity and likelihood ratio of findings for risk stratification in patients suspected of NSTE-ACS. RESULTS: In total, 15 prospective studies were included; these studies reflected in total 26 083 patients. No specific variables related to symptoms, physical examination or risk factors were useful in risk stratification for NSTE-ACS diagnosis. The most useful electrocardiographic finding was ST-segment depression (LR+3.85 (95% CI 2.58 to 5.76)). Point-of-care troponin was found to be a strong predictor for NSTE-ACS in primary care (LR+14.16 (95% CI 4.28 to 46.90) and EMS setting (LR+6.16 (95% CI 5.02 to 7.57)). Combined risk scores were the best for risk assessment in an NSTE-ACS. From the combined risk scores that can be used immediately in a prehospital setting, the PreHEART score, a validated combined risk score for prehospital use, derived from the HEART score (History, ECG, Age, Risk factors, Troponin), was most useful for risk stratification in patients with NSTE-ACS (LR+8.19 (95% CI 5.47 to 12.26)) and for identifying patients without ACS (LR-0.05 (95% CI 0.02 to 0.15)). DISCUSSION: Important study limitations were verification bias and heterogeneity between studies. In the prehospital setting, several diagnostic tools have been reported which could improve risk stratification, triage and early treatment in patients suspected for NSTE-ACS. On-site assessment of troponin and combined risk scores derived from the HEART score are strong predictors. These results support further studies to investigate the impact of these new tools on logistics and clinical outcome. FUNDING: This study is funded by ZonMw, the Dutch Organisation for Health Research and Development. TRIAL REGISTRATION NUMBER: This meta-analysis was published for registration in PROSPERO prior to starting (CRD York, CRD42021254122).</p

Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients

Gaucher disease (GD) is the most common lysosomal storage disorder (LSD). Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs).Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD

Initial rhythm control with cryoballoon ablation vs drug therapy: Impact on quality of life and symptoms

Background Cryoballoon ablation (CBA) as a first-line rhythm control strategy is superior to antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrence; the impact of first-line CBA on quality of life (QoL) and symptoms has not been well characterized. Methods Patients aged 18 to 75 with symptomatic paroxysmal AF naïve to rhythm control therapy were randomized (1:1) to CBA (Arctic Front Advance, Medtronic) or AAD (Class I or III). Symptoms and QoL were assessed at baseline, 1, 3, 6, 9, and 12 months using the EHRA classification and Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and SF-36v2 questionnaires. Symptomatic palpitations were evaluated via patient diary. Results Overall, 107 patients were randomized to CBA and 111 to AAD; crossovers occurred in 9%. Larger improvements in the AFEQT summary, subscale and treatment satisfaction scores were observed at 12 months with CBA vs AAD (all P <0.05). At 12 months, the mean adjusted difference in the AFEQT summary score was 9.9 points higher in the CBA group (95% CI: 5.5 –14.2, P <0.001). Clinically important improvements in the SF-36 physical and mental component scores were observed at 12 months in both groups, with no significant between group differences at this timepoint. In the CBA vs AAD group, larger improvements in EHRA class were observed at 6, 9 and 12 months (P <0.05) and the incidence rate of symptomatic palpitations was lower (4.6 vs 15.2 days/year post-blanking; IRR: 0.30, P <0.001). Conclusions In patients with symptomatic AF, first-line CBA was superior to AAD for improving AF-specific QoL and symptoms.publishedVersio

Validation of mean upper cervical cord area (MUCCA) measurement techniques in multiple sclerosis (MS): High reproducibility and robustness to lesions, but large software and scanner effects

INTRODUCTION: Atrophy of the spinal cord is known to occur in multiple sclerosis (MS). The mean upper cervical cord area (MUCCA) can be used to measure this atrophy. Currently, several (semi-)automated methods for MUCCA measurement exist, but validation in clinical magnetic resonance (MR) images is lacking. METHODS: Five methods to measure MUCCA (SCT-PropSeg, SCT-DeepSeg, NeuroQLab, Xinapse JIM and ITK-SNAP) were investigated in a predefined upper cervical cord region. First, within-scanner reproducibility and between-scanner robustness were assessed using intra-class correlation coefficient (ICC) and Dice's similarity index (SI) in scan-rescan 3DT1-weighted images (brain, including cervical spine using a head coil) performed on three 3 T MR machines (GE MR750, Philips Ingenuity, Toshiba Vantage Titan) in 21 subjects with MS and 6 healthy controls (dataset A). Second, sensitivity of MUCCA measurement to lesions in the upper cervical cord was assessed with cervical 3D T1-weighted images (3 T GE HDxT using a head-neck-spine coil) in 7 subjects with MS without and 14 subjects with MS with cervical lesions (dataset B), using ICC and SI with manual reference segmentations. RESULTS: In dataset A, MUCCA differed between MR machines (p  0.176). However, there was an effect of method for both volumetric and voxel wise agreement of the segmentations (both p < 0.001). Highest volumetric and voxel wise agreement was obtained with Xinapse JIM (ICC absolute agreement = 0.940 and median SI = 0.962). CONCLUSION: Although MUCCA is highly reproducible within a scanner for each individual measurement method, MUCCA differs between scanners and between methods. Cervical cord lesions do not affect MUCCA measurement performance