Prediction of All-Cause Mortality Using an Echocardiography-Based Risk Score in Hemodialysis Patients

<b><i>Aim:</i></b> To derive an echocardiography-based prognostic score for a 3-year risk of mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). <b><i>Methods:</i></b> 173 ESRD patients hospitalized in the second affiliated hospital of Soochow University from January 1, 2010, to July 31, 2016, were enrolled and followed up for 3 years. All subjects began to receive HD from recruitment. Baseline clinical and echocardiographic parameters were collected and screened for risk factors using univariate and multivariate analysis. The prognostic value of echocardiographic indexes was determined by concordance indexes and reclassification assay. Restricted cubic spline models (RCS) and forest plots were employed to visualize the association between risk factors and all-cause mortality. A multivariate nomogram including the identified factors was developed to estimate the prognosis. <b><i>Results:</i></b> After multivariate adjustment for advanced age, hypertension, diabetes, and decreased hemoglobin (Hb), echocardiographic indexes including left atrial diameter index (LADI), cardiac valvular calcification, and moderate to severe cardiac valve regurgitation were independently associated with the risk of 3-year mortality in HD patients. RCS showed that age, Hb, and LADI were positively associated with the risk of mortality. Adding multiple echocardiographic indexes to a basic model containing age, hypertension, diabetes, and Hb increased the concordance index and improved reclassification. A multivariate Cox model-derived nomogram showed the association between each factor and mortality by the end of follow-up. <b><i>Conclusions:</i></b> Echocardiographic indexes showed independent predictive power for mortality in ESRD patients and may constitute a promising prognostic tool in this population.

Safety of long-term treatment with cabergoline on cardiac valve disease in patients with prolactinomas

ObjectiveCabergoline (CAB) has been found to be associated with increased risk of cardiac valve regurgitation in Parkinson's disease, whereas several retrospective analyses failed to detect a similar relation in hyperprolactinemic patients. The current study aimed at investigating cardiac valve disease before and after 24 and 60 months of continuous treatment with CAB only in patients with hyperprolactinemia.Subjects and methodsForty patients (11 men and 29 women, aged 38.7±12.5 years) newly diagnosed with hyperprolactinemia entered the study. Cumulative CAB dose ranged from 12 to 588 mg (median 48 mg) at 24 months and 48–1260 mg (median 149 mg) at 60 months. All patients underwent a complete trans-thoracic echocardiographic examination. Valve regurgitation was assessed according to the American Society of Echocardiography.ResultsAt baseline, the prevalence of trace mitral, aortic, pulmonic, and tricuspid regurgitations was 20, 2.5, 10, and 40% respectively, with no patient showing clinically relevant valvulopathy. After 24 months, no change in the prevalence of trace mitral (P=0.78) and pulmonic (P=0.89) regurgitations and of mild aortic (P=0.89) and tricuspid (P=0.89) regurgitations was found when compared with baseline. After 60 months, the prevalence of trace tricuspid regurgitation was only slightly increased when compared with that after 24 months (37.5%; P=0.82), but none of the patients developed significant valvulopathy. No correlation was found between cumulative dose and prevalence or grade of valve regurgitation at both evaluations. Prolactin levels normalized in all patients but one.ConclusionCAB does not increase the risk of significant cardiac valve regurgitation in prolactinomas after the first 5 years of treatment.

The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis

Implantation of a retrogradely shed endometrium during menstruation requires an adequate blood supply, which allows the growth of endometriotic lesions. This suggests that the development of endometriosis can be impaired by inhibiting angiogenesis. The growth of endometriotic foci is impaired by commercial oncological antiangiogenic drugs used to block vascular endothelial growth factor (VEGF) signaling. The dopamine agonist cabergoline (Cb2) inhibits the growth of established endometriosis lesions by exerting antiangiogenic effects through VEGFR2 inactivation. However, the use of ergot-derived Cb2 is associated with an increased incidence of cardiac valve regurgitation. To evaluate the potential usage of non-ergot-derived dopamine agonists for the treatment of human endometriosis, we compared the efficacy of quinagolide with that of Cb2 in preventing angiogenesis and vascularization in a heterologous mouse model of endometriosis. Nude mice whose peritoneum had been implanted with eutopic human endometrial fragments were treated with vehicle, 50 μg/kg per day oral Cb2, or 50 or 200 μg/kg per day quinagolide during a 14-day period. At the end of the treatment period, the implants were excised in order to assess lesion size, cell proliferation, degree of vascularization, and angiogenic gene expression. Neoangiogenesis was inhibited and the size of active endometriotic lesions, cellular proliferation index, and angiogenic gene expression were significantly reduced by both dopamine agonists when compared with the placebo. Given that Cb2 and quinagolide were equally effective in inhibiting angiogenesis and reducing lesion size, these experiments provide the rationale for pilot studies to explore the use of non-ergot-derived dopamine agonists for the treatment of endometriosis in humans.