Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart.
Right heart function is the main determinant of prognosis in pulmonary arterial hypertension (PAH). At present, no treatments are currently available that directly target the right ventricle, as we will demonstrate in this article. Meta-analysis of clinical trials in PAH revealed that current PAH medication seems to have limited cardiac-specific effects when analysed by the pump-function graph. Driven by the hypothesis that "left" and right heart failure might share important underlying pathophysiological mechanisms, we evaluated the clinical potential of left heart failure (LHF) therapies for PAH, based on currently available literature. As in LHF, the sympathetic nervous system and the renin-angiotension-aldosterone system are highly activated in PAH. From LHF we know that intervening in this process, e.g. by angiotensin-converting enzyme inhibition or β-blockade, is beneficial in the long run. Therefore, these medications could be also beneficial in PAH. Furthermore, the incidence of sudden cardiac death in PAH could be reduced by implantable cardioverter-defibrillators. Finally, pilot studies have demonstrated that interventricular dyssynchrony, present at end-stage PAH, responded favourably to cardiac resynchronisation therapy as well. In conclusion, therapies for LHF might be relevant for PAH. However, before they can be implemented in PAH management, safety and efficacy should be evaluated first in well-designed clinical trials.
Handoko
M L
ML
Dept. of Physiology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
de Man
F S
FS
Allaart
C P
CP
Paulus
W J
WJ
Westerhof
N
N
Vonk-Noordegraaf
A
A
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D002304:Cardiac Pacing, Artificial; D003131:Combined Modality Therapy; D017147:Defibrillators, Implantable; D065627:Familial Primary Pulmonary Hypertension; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy
D000319:Adrenergic beta-Antagonists