Neurohormonal modulation: The new paradigm of pharmacological treatment of heart failure.

The current paradigm of medical therapy for heart failure with reduced ejection fraction (HFrEF) is triple neurohormonal blockade with an angiotensin-converting enzyme inhibitor (ACEI), a beta-blocker (BB) and a mineralocorticoid receptor antagonist (MRA). However, three-year mortality remains over 30%. Stimulation of counter-regulatory systems in addition to neurohormonal blockade constitutes a new paradigm, termed neurohormonal modulation. Sacubitril/valsartan is the first element of this new strategy. PARADIGM-HF was the largest randomized clinical trial conducted in HFrEF. It included 8442 patients and compared the efficacy and safety of sacubitril/valsartan versus enalapril. The primary endpoint was the composite of cardiovascular mortality and hospitalization due to HF, which occurred in 914 (21.8%) patients receiving sacubitril/valsartan and in 1117 (26.5%) patients receiving enalapril (HR 0.8, 95% CI 0.73-0.87, p=0.0000002; NNT 21). Sacubitril/valsartan reduced both primary endpoint components, as well as sudden cardiac death, death due to worsening HF, and death from all causes. Patients on sacubitril/valsartan reported less frequent deterioration of HF and of quality of life, and discontinued study medication less frequently because of an adverse event. PARADIGM-HF demonstrated the superiority of sacubitril/valsartan over enalapril, with a 20% greater impact on cardiovascular mortality compared to ACEIs. Accordingly, in 2016, the European (ESC) and American (ACC/AHA/HFSA) cardiology societies simultaneously issued a class I recommendation for the replacement of ACEIs by sacubitril/valsartan in patients resembling PARADIGM-HF trial participants.

[Invasive pulmonary aspergillosis]. / Aspergilose pulmonar invasiva.

Aspergillosis, the most frequent of pulmonary mycosis, represents a group of varying pathogenesis diseases with the same etiological agent--Aspergillus. This fungus is a saprophyte of normal respiratory airways, but the disease occurs in immunocompromised hosts. There are several anatomo-clinical forms, but it is important to know that some could be fatal, being necessary an early diagnosis and therapy. The authors describe an Invasive Pulmonary Aspegillosis case, in a immunocompromised patient submitted to long term corticotherapy treatment. Was started with liposomal Amphotericin B, discontinued due to nephrotoxicity and substituted by Itraconazol, with clinical, laboratorial and radiologic favourable evolution, as it's proven by imagiological studies.

[Gangrenous cystitis]. / Cistite gangrenosa.

Gangrenous cystitis is a rare condition, there are no typical symptoms or clinical findings, which hampers diagnosis and may worsen the prognosis. The authors report the case of a diabetic male patient, hospitalized because of poor general condition, dehydration and diffuse abdominal pain. The diagnosis was made by typical pelvic CT findings. Medical treatment must be intensive and begun as soon as possible. As in the present case, the situation may have a favorable outcome.