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Dr. Simon Gibbs,
Left heart disease in patients with pulmonary hypertension is a hot topic and will make a fruitful area for research in the next decade. The crucial questions to ask are why some patients develop pulmonary hypertension and what treatment they should receive.
Heart failure with reduced ejection fraction, preserved ejection fraction and valve disease can lead to pulmonary hypertension. The driving factor in each case is raised left atrial pressure which results in an inevitable rise in pulmonary artery pressure to maintain flow. Some patients then develop pulmonary vascular remodelling with a consequent rise in pulmonary vascular resistance.
It is this last group that could be a target for drug therapies directed at the pulmonary circulation in patients with heart failure with preserved ejection fraction. Such investigation must proceed with caution given a past history of clinical deterioration in trials of prostacyclin and endothelin receptor antagonists in patients with systolic heart failure, albeit not selected for having pulmonary hypertension. Furthermore a trial of sildenafil in heart failure with preserved ejection fraction did not show benefit over placebo.
Since the mechanism of pulmonary hypertension driven by left heart disease is quite different from pulmonary arterial hypertension for which these drugs were initially conceived, perhaps the lack of efficacy is unsurprising. For patients with pulmonary hypertension related to heart failure with preserved ejection fraction this leaves patients in a quandary: there is no evidence based treatment for the myocardium or the pulmonary hypertension.
There is an urgent need to address this and new trials to treat the pulmonary circulation using riociguat and also macitentan may go some way to providing an answer.
Pulmonary hypertension in left heart disease: marker or target?
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