Félix, Iuri Ferreira

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy typically transmitted in an autosomal dominant fashion. There is growing importance in identifying genetic test positive patients given its prognostic value. The Mayo HCM Genotype Predictor Score has been extensively validated for assessment of patient’s pre-test probability for genotype positive HCM and helps guide clinical decision-making based on clinical and echocardiographic variables. Herein, we evaluated the role of cardiac magnetic resonance (CMR) to enhance the genotype predictor score. Purpose Evaluate performance of the Mayo Clinic HCM Genotype Predictor Score using CMR variables, and develop an updated, CMR incorporated score. Methods Retrospective analysis was conducted on 175 unrelated HCM patients with at least 1 MRI and a HCM genetic testing seen at the Mayo Clinic between April 2004 and April 2018. Phenotyping information was obtained through review of electronic medical records. The original Mayo HCM Genotype Predictor Score was calculated using both echocardiography and clinical variables. An updated score was created incorporating CMR-specific variables. Diagnostic accuracy of the models was assessed thought Receiver Operating Characteristic (ROC) curves. Results Overall, 108 (62%) were males with a mean age at CMR of 51 ± 18 years. The yield of positive genetic test for the echocardiogram-derived Mayo HCM Genotype Predictor Score ranged from 38% for patients with -1 point to 100% for patients with 4 or 5 points. There was a significant incremental increase in diagnostic yield between score subgroups (p < 0.01) with an AUC of 0.659 (Figure 1A). Similar findings were observed using CMR variables (AUC of 0.697; Figure 1B). Univariate and multivariate analysis identified late gadolinium enhancement (LGE) as a strong predictor of a positive genetic test (OR 3.72; p=0.002), and it was added to the original score to create a new version. The Updated Mayo HCM Genotype Predictor Score predicted a positive genetic test ranging from 25% for patients with -1 point to 100% for patients with 5 or 6 points (p < 0.01). There was a significant increase in diagnostic accuracy when compared to the original score (AUC 0.724 vs 0.679; p=0.03; Figure 1C). Conclusion Using LGE, the updated CMR-based Mayo HCM Genotype Predictor score provides a simple and improved tool to aid in genetic counseling for HCM patients.

Abstract Importance Menopausal hormone therapy (HT) includes a wide variety of hormonal compounds, and its effect on blood pressure is still uncertain. Objective The aim of this study was to assess evidence regarding the effect of HT on blood pressure in postmenopausal women and its association with arterial hypertension. Evidence Review This systematic review and meta-analysis included randomized clinical trials and prospective observational studies. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of hypertension were assessed. All stages were independently performed by two reviewers. For blood pressure outcome, standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated as effect measures. Heterogeneity was assessed using the I 2 statistic. The results are presented based on the HT type. The incidence of hypertension was compared using descriptive analyses. Findings Eleven studies were included with 81,041 women evaluated, of which 29,812 used HT. The meta-analysis, conducted with 8 studies and 1,718 women, showed an increase in SBP with the use of oral conjugated equine estrogens plus progestogen (SMD = 0.60 mm Hg, 95% CI = 0.19 to 1.01). However, oral or transdermal use of estradiol plus progestogen (SMD = −2.00 mm Hg, 95% CI = −7.26 to 3.27), estradiol alone, and tibolone did not show any significant effect. No significant effect on DBP was observed for any formulation. Women who used oral estrogen plus progestogen had a higher risk of incident hypertension than those who never used it. Conclusions and Relevance The effect of HT on blood pressure is influenced by the formulation used, especially the type of estrogen. The combined formulations of conjugated equine estrogens plus progestogen increased SBP and the risk of hypertension, which was not observed among estradiol plus progestogen, estradiol alone, and tibolone users.