ABC | Volume 114, Nº1, January 2019

Review Article Fernandes et al. Heart Failure with Preserved Ejection Fraction Arq Bras Cardiol. 2020; 114(1):120-129 Digoxin DIG PEF 23 2006 Digoxin vs. placebo 988 LVEF > 40% (mean 53%), sinus rhythm 3.1 years No effect on natural history endpoints such as mortality and hospitalizations (HR 0.82; 95%CI: 0.63–1.07; p = 0.136) Nitrates and Nitrites NEAT HFpEF 24 2015 Isosorbide mononitrate vs. placebo 110 ≥50 years, LVEF ≥ 50%, evidence of HF 6 weeks No effect on quality of life (p = 0.37) or NT-proBNP levels (p = 0.22); Reduction in daily activity level (-381 95%CI -780-17, p = 0.06) and increased symptoms of HF Inorganic nitrate on exercise capacity 25 2015 NO3-rich beetroot juice vs. placebo (single dose) 17 Symptomatic HF, LVEF > 50% 12 days Increased exercise capacity (p = 0.04) (reduction in systemic vascular resistance, increased cardiac output and increased oxygen delivery) Sildenafil RELAX 26 2013 Sildenafil vs. placebo 216 LVEF ≥ 50%, NYHA II‑IV, NT‑proBNP > 400 pg/mL, Peak VO 2  < 60%, or elevated LV filling pressures 24 weeks No effect on exercise capacity (p = 0.90), clinical status (p = 0.85) or diastolic function (p = 0.16). Worsening of renal function, NTproBNP, endothelin-1 and uric acid sCG Stimulators DILATE-1 27 2014 Riociguat vs. placebo (single dose) 39 ≥18 years, LVEF > 50% and PH; mPAP ≥ 25 mmHg and PCWP > 15 mmHg 30 days Well tolerated; improved exploratory hemodynamic and echocardiographic parameters; No impact on mPAP (p = 0.60) SOCRATES- Preserved 28 2016 Vericiguat vs. placebo 470 LVEF ≥ 45%, NYHA II‑IV, elevated natriuretic peptides 12 weeks No effect on NT-proBNP (p = 0.20) or LA volume (p = 0.37). Some potential in improving quality of life (p = 0.016), particularly with higher doses Ranolazine RALI-DHF 29 2013 Ranolazine vs. placebo 20 LVEF ≥ 45%, E/ E` > 15 or NT‑proBNP > 220pg/mL, tau ≥ 50ms, LVEDP ≥ 18 mmHg 14 days Despite hemodynamic improvements at 24 h, there was no effect on diastolic function parameters B Clinical Trial Year Intervention Patients, n Major inclusion criteria Mean follow- up Main conclusions Albuterol BEAT – HFpEF 30 2019 Albuterol vs. placebo 30 LVEF ≥ 50%, elevated LV filling pressures, PCWP > 15 mmHg and/or ≥ 25 mmHg during exercise - Symptom evaluation through its effect on pulmonary vascular resistance at rest and during exercise Shunt REDUCE LAP-HF I 31 2017 Interatrial septal shunt device vs. sham procedure 94 LVEF>40% and elevated PCWP 1 month Showed to be safe and effective; Reduction of PCWP (p = 0.028) without significant increase in PAP or pulmonary vascular resistance Monitoring CHAMPION 34 2014 Hemodynamic monitoring vs. control 119 LVEF > 40% (mean 50.6%), NYHA III 17.6 months Significant reduction in HF hospitalizations (HR 0.50; 95%CI: 0.35–0.70; P < 0.0001) Exercise EX DHF 36 2011 Supervised resistance training vs. usual care 64 > 45 years, LVEF ≥ 50%, NYHA II-III, diastolic dysfunction, sinus rhythm and ≥ 1 CV risk factor 3 months It showed to be achievable, safe and effective; Improved functional capacity, diastolic function and quality of life (´p < 0.001) Comorbidities OPTIMIZE-HFPEF 38 2016 Systematic screening and optimal treatment of comorbidities vs. usual care 360 >60 years, LVEF ≥ 50%, NYHA II‑IV 2 years Assessment of clinical status Pacing RAPID-HF 39 (NCT02145351) 2019 Dual chamber pacemaker with pacing on vs. pacing off 30* LVEF ≥ 50%, NYHA II‑III, diastolic dysfunction and chronotropic incompetence 4 weeks Assessment of exercise capacity, symptoms and quality of life 124