ABC | Volume 113, Nº3, September 2019

Review Article Calderado et al. Pulmonary hypertension Arq Bras Cardiol. 2019; 113(3):419-428 Table 3 – Specific drugs available for PH treatement (modified from Galiè N, et al. 11 ) Pathophysiological pathways Class Drug Endothelin Endothelin Receptor Antagonists 1 Ambrisentan Bosentan Macitentan Nitric Oxide Phosphodiesterase type5 inhibitors Sildenafil Tadalafil Vardenafil Soluble Guanylate Cyclase Stimulants Riociguat Prostaglandins Prostacyclin Epoprostenol Prostacycline Analogues Iloprost Treprostinil Beraprost Selective IP receptor agonists Selexipag Table 2 – Risk assessment in pulmonary arterial hypertension – adpted from the European guidelines on pulmonary hypertension published in 2015 11 Prognostic marker/RisK Low risk (Estimated mortality < 5% year) Intermediate risk (Estimated mortality 5-10% year) High risk (Estimated mortality > 10% year) Signs of heart failure Absent Absent Present Progression of symptoms No Slow Rapid Syncope No Occasional Frequent Functional class I, II III IV 6MWD > 440 m 165-440 m < 165 m Cardiopulmonary exercise testing Peak VO 2 > 15 ml/min/kg (> 65% pred.) VE/VCO 2 slope < 36 Peak VO 2 11-15 ml/min/kg (35-65% pred.) VE/VCO 2 slope 36-44.9 Peak VO 2 < 11ml/min/kg (< 35% pred.) VE/VCO 2 slope ≥ 45 BNP levels BNP < 50 ng/L NT-proBNP < 300 ng/L BNP 50-300 ng/L NT-proBNP 300-1400 ng/L BNP > 300 ng/L NT-proBNP > 1400 ng/L Imaging RA area < 18 cm 2 No pericardial effusion RA area 18-26 cm 2 No or minimal pericardial effusion RA area > 26 cm 2 Pericardial effusion Hemodynamics RAP < 8 mmHg CI ≥ 2.5 l/min/m 2 SvO 2 > 65% RAP 8-14 mmHg CI > 2-2.5 l/min/m 2 SvO 2 60-65% RAP > 14 mmHg CI < 2.0 l/min/m 2 SvO 2 < 60% VO 2 : consumo de oxigênio; VCO 2 : liberação de dióxido de carbono; Slope VE/VCO 2 : equivalente respiratório para o dióxido de carbono; BNP: peptídeo natriurético cerebral; NT pro BNP: fragmento N-terminal do pró BNP; AD: átrio direito; In.C: índice cardíaco; SVO 2 : saturação venosa mista de oxigênio. vs 37%. There was no significant differences in symptoms, quality of life or walking distance. Minor studies have shown conflicting data of clinical and/or hemodynamic improvement, but they had no power to assess mortality. 39 Until today, the use of epoprostenol (or the prostanoid analogs, i.e., iloprost, treprostinil, beraprost, or even selexipag, a specific IP-receptor agonist, which acts on the same pathway as prostaglandins) is not recommended for group 2 PH. Endothelin receptor antagonists Blockade of ETA receptors in patients with group 2 PH can be useful not only for the well-known effects on pulmonary circulation, but also because of its potential direct benefits to the systemic circulation and myocardium. In 1998, Sütsch etal. 40 observed an increase in cardiac output, decrease in pulmonary capillary pressure and severe systemic and pulmonary vascular resistance in a small number of patients with advanced HF, randomized to receive bosentan 1 g (a non-selective inhibitor of endothelin receptors A and B). 40 Four years later, in the ENABLE study, 1,613 patients with NYHA functional class III or IV heart failure due to severe left ventricular dysfunction (EF < 35%) received bosentan (125 mg 2X/day) or placebo; there was no difference in the primary outcome (death or hospitalization due to heart failure) and there was higher fluid retention in the group who had received the medication. 41,42 In the HEAT study, 157 patients with FC III HF (and cardiac index ≤ 2.6 L/min.m 2 and PCP ≥ 12 mmHg) were randomized to receive placebo or darusentan (a selective inhibitor of endothelin receptor A). The group who received darusentan showed increased cardiac index (the study's 423