Packer et al Angiotensin Neprilysin Inhibition in Heart Failure 55Background-Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. Methods and Results-We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensinconverting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-Btype natriuretic peptide and troponin) versus enalapril. Conclusions-Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. (Circulation. 2015;131:54-61.
Рабочая группа по диагностике и лечению гипертрофической кардиомиопатии Европейского общества кардиологов (ESC)Авторы/члены рабочей группы: perry M. Elliott* (Председатель) (великобритания) Aris Anastasakis (Греция), Michael A. borger (Германия), Martin borggrefe (Германия), Franco Cecchi (Италия), philippe Charron (Франция), Albert Alain Hagege (Франция), Antoine Lafont (Франция), Giuseppe Limongelli (Италия), Heiko Mahrholdt (Германия), William J. McKenna (великобритания), Jens Mogensen (дания), petros Nihoyannopoulos (великобритания), Stefano Nistri (Италия), petronella G. pieper (Нидерланды), burkert pieske (Австрия), Claudio Rapezzi (Италия), Frans H. Rutten (Нидерланды), Christoph Tillmanns (Германия), Hugh Watkins (великобритания). Дополнительный участник: Constantinos O'Mahony (великобритания).Комитет ESC по подготовке практических рекомендаций (КПР): Jose Luis Zamorano (Председатель) (Испания), Stephan Achenbach (Германия), Helmut baumgartner (Германия), Jeroen J. bax (Нидерланды), Héctor bueno (Испания), Veronica Dean (Франция), Christi Deaton (великобритания), Çetin Erol (Турция), Robert Fagard (Бельгия), Roberto Ferrari (Италия), David Hasdai (Израиль), Arno W. Hoes (Нидерланды), paulus Kirchhof (Германия/великобритания), Juhani Knuuti (Финляндия), philippe Kolh (Бельгия), patrizio Lancellotti (Бельгия), Ales Linhart (Чехия), petros Nihoyannopoulos (великобритания), Massimo F. piepoli (Италия), piotr ponikowski (Польша), per Anton Sirnes (Норвегия), Juan Luis Tamargo (Испания), Michal Tendera (Польша), Adam Torbicki (Польша), William Wijns (Бельгия), Stephan Windecker (Швейцария).Рецензенты: David Hasdai (Израиль) (КПР координатор рецензирования), piotr ponikowski (Польша) (КПР координатор рецензирования), Stephan Achenbach (Германия), Fernando Alfonso (Испания), Cristina basso (Италия), Nuno Miguel Cardim (Португалия), Juan Ramón Gimeno (Испания), Stephane Heymans (Нидерланды), per Johan Holm (Швеция), Andre Keren(Израиль), paulus Kirchhof (Германия/великобритания), philippe Kolh (Бельгия), Christos Lionis (Греция), Claudio Muneretto (Италия), Silvia priori (Италия), Maria Jesus Salvador (Испания), Christian Wolpert (Германия), Jose Luis Zamorano (Испания).Формы раскрытия конфликта интересов авторов и рецензентов рекомендаций доступны на сайте ESC www.escardio.org/guidelines
Fabry disease (FD) is an X-linked genetic disorder caused by the deficient activity of lysosomal α-galactosidase (α-Gal). While males are usually severely affected, clinical presentation in female patients may be more variable ranging from asymptomatic to, occasionally, as severely affected as male patients. The aim of this study was to evaluate the existence of skewed X-chromosome inactivation (XCI) in females with FD, its concordance between tissues, and its contribution to the phenotype. Fifty-six females with FD were enrolled. Clinical and biological work-up included two global scores [Mainz Severity Score Index (MSSI) and DS3], cardiac magnetic resonance imaging, measured glomerular filtration rate, and measurement of α-Gal activity. XCI was analyzed in four tissues using DNA methylation studies. Skewed XCI was found in 29% of the study population. A correlation was found in XCI patterns between blood and the other analyzed tissues although some punctual variability was detected. Significant differences in residual α-Gal levels, severity scores, progression of cardiomyopathy and deterioration of kidney function, depending on the direction and degree of skewing of XCI were evidenced. XCI significantly impacts the phenotype and natural history of FD in females.
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