Right ventricular systolic strain in patients with pulmonary hypertension: clinical feasibility, reproducibility, and correlation with ejection fraction.

BACKGROUND: Right ventricular (RV) systolic function is the major determinant of prognosis in patients with pulmonary hypertension (PH) with quantitative assessment by speckle-tracking strain echocardiography emerging as a viable candidate measure. METHOD: We evaluated a prospective cohort of 231 patients with known or suspected PH referred for clinical echocardiography. All underwent measurement of RV free-wall systolic strain by sonographer staff. Digital images were recorded for blinded offline assessment by an expert echocardiographer. Reproducibility was assessed using the analysis methods of Bland-Altman and the Cohen's-Kappa coefficient. RESULTS: RV strain was feasible in 213 (92%). The average RV systolic pressure was 59 ± 22 mmHg. RV systolic strain correlated with functional class, NT-proBNP, and the degree of RV enlargement. The average free-wall systolic strain was - 20 ± 7% (range - 2 to - 37%). The RV strain measures (clinical practice versus blinded expert) had an excellent correlation with a normal distribution (R2 0.87, p < 0.0001). By Bland-Altman analysis, the mean difference in measurement was - 1.7% (95% CI - 1.4 to - 2.1) with a correlation of 0.93, p value of < 0.0001. The reproducibility of RV strain for clinically relevant thresholds was also excellent (Kappa coefficients 0.68-0.83). There was no effect on the variability of strain measures across body mass, pulmonary pressures, or rhythm. RV strain correlated with RV diastolic volumes and ejection fraction with RV free wall strain being the best echo predictor for a reduction in ejection fraction. CONCLUSION: Here RV systolic strain was found to be highly feasible and reproducible in clinical practice with excellent levels of agreement for clinically relevant thresholds.

CYP2C19 polymorphisms in the Thai population and the clinical response to clopidogrel in patients with atherothrombotic-risk factors.

Genetic variation in the cytochrome P450 2C19 (CYP2C19) gene has been documented gradually as the determinant conversion and variability in the antiplatelet effect of clopidogrel. The aims of this study were to determine the prevalence of clinically relevant allele variants (CYP2C19*2, CYP2C19*3, and CYP2C19*17) in a Thai study population, and finally determine whether the allele distributes and predicts metabolic phenotypes in clopidogrel treated patients. A total of 1,051 Thai patients participated in this study. Genotypes for CYP2C19 polymorphisms were detected by the microarray-based technique. Furthermore, results of genotyping and platelet aggregation in 96 cardiovascular disease patients on 75 mg clopidogrel maintenance daily dose therapy also were analyzed. Among 1,051 samples, the allele frequencies of CYP2C19 *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *1/*17 were found in 428 (40.72%), 369 (35.10%), 72 (6.85%), 77 (7.32%), 59 (5.61%), and 45 (4.30%) of the patients, respectively. Homozygous CYP2C19 *3/*3 was found in one patient (0.10%). Therefore, 40.72% of the patients were predicted as extensive metabolizers, 41.95% as intermediate metabolizers, 13.03% as poor metabolizers, and 4.30% as ultra-rapid metabolizers. Among 96 patients, the frequency of poor metabolizers was significantly higher in the clopidogrel non-responder group than in the responder group (36.0% and 15.5%, respectively, P = 0.03). CYP2C19*1/*17 was observed in responders (n = 2; 2.8%). As a result, CYP2C19 variants were associated with clopidogrel non-responders. However, there is a need for further elucidation of the clinical importance and use of this finding to make firm and cost-effective recommendations for drug treatment in the future.