The effects of phosphodiesterase 5 inhibition on hemodynamics, functional status and survival in advanced heart failure and pulmonary hypertension: a case-control study.
BACKGROUND
The goal was to examine the hemodynamic and clinical effects of long-term therapy with PDE5 inhibitor sildenafil (SILD) in patients with advanced, pre-transplant heart failure (HF) and severe pulmonary hypertension (PH), in comparison to a similar control group (CON).


METHODS
In this non-randomized, retrospective case-control study, 32 middle-aged patients (81% males) with advanced systolic HF (80%≥ NYHA III, 56% ischemic) and severe pre-capillary PH (transpulmonary pressure gradient>15 mm Hg) were studied before and after initiation of SILD (dose 73 ± 25 mg/day) and were compared to 15 CON patients, matched for key clinical characteristics (including PH severity, age and co-morbidities), not exposed to SILD. Changes at 3 months and the long-term outcome were compared between groups.


RESULTS
SILD significantly reduced pulmonary vascular resistance (-32% vs. baseline), transpulmonary gradient (-25%) and increased cardiac output (+15%) compared to controls, without affecting systemic or ventricular filling pressures. SILD-treated subjects experienced an improvement in NYHA class and had a steady body weight which contrasted with significant weight loss in the CON group (by -4.8%, absolutely by 4.3 ± 6 kg). During follow-up (median 349 days from baseline), 60% of patients underwent heart transplantation. Two patients in CON group had severe post-transplant failure of the right ventricle, none in SILD group. Overall pre- and peritransplant survival (censored 30 days after transplantation) was significantly better in SILD than CON group (93.7 vs 60%, p=0.0048).


CONCLUSIONS
In patients with advanced HF and severe PH, SILD therapy has beneficial effects on hemodynamics, clinical status, cardiac cachexia, and contributes to improved peri-transplant survival.
Department of Cardiology, Institute of Clinical and Experimental Medicine - IKEM, Prague, Czech Republic.
Adrian
A
Reichenbach
Hikmet
H
Al-Hiti
Ivan
I
Malek
Jan
J
Pirk
Eva
E
Goncalvesova
Josef
J
Kautzner
Vojtech
V
Melenovsky
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
D058986:Phosphodiesterase 5 Inhibitors