Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis

Objective To evaluate the accumulated information from genetic association studies investigating the impact of variants of the cytochrome P450 (CYP) 2C19 genotype on the clinical efficacy of clopidogrel

Early onset and progression of left ventricular remodeling after alcohol septal ablation in hypertrophic obstructive cardiomyopathy

Background - Alcohol septal ablation (ASA) reduces left ventricular outflow tract (LVOT) pressure gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM), which leads to left ventricular remodeling. We sought to describe the early to midterm changes and modulating factors of the remodeling process using cardiac MRI (CMR). Methods and Results - CMR was performed at baseline and 1 and 6 months after ASA in 29 patients with HOCM (age 52±16 years). Contrast-enhanced CMR showed no infarct-related hyperenhancement outside the target septal area. Septal mass decreased from 75±23 g at baseline to 68±22 and 58±19 g (P<0.001) at 1- and 6-month follow-up, respectively. Remote, nonseptal mass decreased from 141±41 to 132±40 and 111±27 g (P<0.001), respectively. Analysis of temporal trends revealed that septal mass reduction was positively associated with contrast-enhanced infarct size and transmural or left-sided septal infarct location at both 1 and 6 months. Remote mass reduction was associated with infarct location at 6 months but not with contrast-enhanced infarct size. By linear regression analysis, percentage remote mass reduction correlated significantly with LVOT gradient reduction at 6-month follow-up (P=0.03). Conclusions - Left ventricular remodeling after ASA occurs early and progresses on midterm follow-up, modulated by CMR infarct size and location. Remote mass reduction is associated with infarct location and correlates with reduction of the LVOT pressure gradient. Thus, myocardial hypertrophy in HOCM is, at least in part, afterload dependent and reversible and is not exclusively caused by the genetic disorder

The Clinical Implementation of CYP2C19 Genotyping in Patients with an Acute Coronary Syndrome:Insights From the FORCE-ACS Registry

BACKGROUND: Guidelines recommend prasugrel or ticagrelor for acute coronary syndrome (ACS) patients. However, these P2Y12 inhibitors increase bleeding risk compared to clopidogrel. Although genotype-guided P2Y12-inhibitor selection has been shown to reduce bleeding risk, data on its clinical implementation is lacking. METHODS: The study included ACS patients receiving genotype-guided antiplatelet therapy, utilising either a point-of-care (POC) device or laboratory-based testing. We aimed to collect qualitative and quantitative data on genotyping, eligibility for de-escalation, physician adherence to genotype results, time to de-escalation and cost reduction. RESULTS: Of the 1,530 patients included in the ACS registry from 2021 to 2023, 738 ACS patients treated with ticagrelor received a CYP2C19 genotype test. The median turnover time of genotyping was 6.3 hours (interquartile range [IQR], 3.2-16.7), with 82.3% of the genotyping results known within 24 hours after admission. POC genotyping exhibited significantly shorter turnaround times compared to laboratory-based testing (with respective medians of 5.7 vs 47.8 hours; P &lt; .001). Of the genotyped patients, 81.7% were eligible for de-escalation which was carried out within 24 hours in 70.9% and within 48 h in 93.0%. The time to de-escalation was significantly shorter using POC (25.4 hours) compared to laboratory-based testing (58.9 hours; P &lt; .001). Implementing this strategy led to a reduction of €211,150.50 in medication costs. CONCLUSIONS: CYP2C19 genotype-guided-de-escalation in an all-comers ACS population is feasible. POC genotyping leads to shorter turnaround times and quicker de-escalation. Time to de-escalation from ticagrelor to clopidogrel in noncarriers was short, with high physician adherence to genotype results.</p

The validity and precision of the leicester cough questionnaire in COPD patients with chronic cough

Background: A validated instrument to assess the effects of chronic cough on health status in patients with chronic obstructive pulmonary disease (COPD) is currently not available. The Leicester Cough Questionnaire (LCQ) is a cough-specific health status questionnaire which is originally validated for a population of general patients presenting with chronic cough. We examined the psychometric performance of the LCQ in patients with COPD and chronic productive cough. Methods: Concurrent validity, internal consistency, reproducibility and responsiveness were determined. The St. George's Respiratory Questionnaire (SGRQ) and the Short Form-36 (SF-36) were used as external criteria. Questionnaires were completed at the start of the study. After 2 and 12 weeks the LCQ was repeated, together with a global rating of change. Results: In total 54 patients were included. Concurrent validity analysis showed significant correlations between corresponding domains of the LCQ and the SGRQ (r(s) - 0.31 to - 0.60). Corresponding domains of the LCQ and the SF-36 showed weaker correlations (r(s) 0.04 to 0.41). Internal consistency was adequate for two of the three domains (Cronbach's alpha 0.74 - 0.86). Test-retest reliability in stable patients was high (intraclass correlation coefficients 0.79 - 0.93). The mean difference after two weeks was 0.73 (+/- 1.75). Responsiveness analysis indicated that the LCQ was able to detect changes after 12 weeks. Conclusion: The LCQ is a valid, reliable, responsive instrument to measure health status in COPD patients with chronic productive cough

The Relationship between Nociceptive Detection Thresholds and Pressure-and Electrical Pain Thresholds:An Explorative Study in Rheumatoid Arthritis Patients

Recently, methods have been developed enabling the characterization of the nociceptive function at the detection threshold level by measuring nociceptive detection thresholds (NDTs), rather than at the level of the pain threshold via pain threshold (PT) measurements. Both NDT and PT measurements aim to characterize (parts of) the nociceptive system. To date it is unclear if, and if so to what extent, the two outcomes relate to one another. In this study, the primary aim is to explore the relationship between the two measures in patients with rheumatoid arthritis (RA). As secondary aim, we explore differences in NDT between these RA patients with age-and sex-matched healthy controls (HC) from a readily existing dataset. In total 46 RA patients have been recruited, whereby the pressure-(PPT; bilaterally at two locations) and electrical (EPT) pain threshold were evaluated, as well as the NDTs. Significant, positive correlations were found between the EPT and PPT (R=0.54-0.60), but not with the NDTs (R≤0.25). As compared to HC, higher NDTs were found in the RA group. As the presence of a statistically significant weak relationship can only be evaluated using a larger sample size, our results indicate that there is no moderate or stronger relation between PT and NDT outcomes. This implicates that the two outcomes are not strongly driven by the same (nociceptive) mechanism(s). Future research into NDTs and what factors and/or mechanisms affect the outcome, could yield relevant insights into how to use and interpret the results of this relatively new method.Clinical Relevance-The evaluation of nociceptive detection thresholds, in isolation or together with conventionally evaluated pain thresholds, might provide valuable and complementary insights into nociceptive (dis)function in man.</p

aspirin therapy in primary cardiovascular disease prevention a position paper of the european society of cardiology working group on thrombosis

Although the use of oral anticoagulants (vitamin K antagonists) has been abandoned in primary cardiovascular prevention due to lack of a favorable benefit-to-risk ratio, the indications for aspirin use in this setting continue to be a source of major debate, with major international guidelines providing conflicting recommendations. Here, we review the evidence in favor and against aspirin therapy in primary prevention based on the evidence accumulated so far, including recent data linking aspirin with cancer protection. While awaiting the results of several ongoing studies, we argue for a pragmatic approach to using low-dose aspirin in primary cardiovascular prevention and suggest its use in patients at high cardiovascular risk, defined as $2 major cardiovascular events (death, myocardial infarction, or stroke) projected per 100 person-years, who are not at increased risk of bleeding. (J Am Coll Cardiol 2014;64:319–27) © 2014 by the American College of Cardiology Foundation