Sunday, July 19, 2015

Pulmonary arterial hypertension as a medium-term risk of death in patients ith heart failure


A decade ago, the diagnosis of pulmonary arterial hypertension (PAH) heralded a uniformly poor prognosis. Progress has come in recent years via the development of carefully targeted therapies.
Heart failure (HF) is one of the most common causes of PH, - See more at: http://www.acc.org/latest-in-cardiology/articles/2015/04/14/15/21/left-heart-disease-check-for-pulmonary-hypertension-practical-approaches-to-the-management-of-pulmonary-hypertension#sthash.aXt4vyUX.dpuf

A growing appreciation that pulmonary hypertension (PH) in left heart disease (LHD) signals poor prognosis has led to a flurry of investigational activity.
Heart failure (HF) is one of the most common causes of PH.
There was a strong, positive, graded association between PA (Pulmonary Artery)  systolic pressure and subsequent mortality that was independent of age, sex, comorbidities, EF, and diastolic function. The investigators found that PA systolic pressure strongly predicted medium-term risk of death in patients with HF( Heart failure)  and improved prediction of death and CV death over traditional prognostic factors. Importantly, PH
( pulmonary hypertension ) appeared to be not only a marker of worse HF, but also to have direct deleterious effects.

PH   in HF has been postulated to result from the combination of the passive effect of elevated left ventricular end-diastolic pressure backward on the pulmonary venous circulation and an active vasoreactive process of vasoconstriction and PA remodeling. Pathology studies have shown remodeling changes in the elastic fibers of the pulmonary arterial wall, intimal fibrosis, and medial hypertrophy of pulmonary muscular arteries, with changes that are similar to or greater than those seen in idiopathic PAH.


Although PAH and PH secondary to LHD share a final common hemodynamic and prognostic outcome, translational investigations have suggested fundamental differences in the cellular basis and in outcomes related to pharmacological modulation of neurohormonal pathways in these distinct states. For example, the presence of the angiotensin-converting enzyme DD genotype is associated with adverse survival in LV failure, whereas in PAH, there are signals supporting a compensatory role in preserving right ventricular (RV) function. Similarly, beta-adrenergic neuroeffector pathways demonstrate distinct differences between right-side HF due to PAH or PH secondary to LHD.

 
Despite evidence for the expression of endothelin-1 excess in both PAH and LHD states, the outcome of targeting the aberration through endothelin antagonists is quite dissimilar, with a marked evidence of benefit in PAH but notable worsening in the context of LHD. Conversely, therapeutic modulation of the nitric oxide pathway with the use of phosphodiesterase-5 inhibitors may be equally beneficial between the two distinct syndromes of PAH and PH due to LHD.

Reference:

LeftHeart Disease? Check for Pulmonary Hypertension: Practical Approaches to theManagement of Pulmonary Hypertension
PH in HF has been postulated to result from the combination of the passive effect of elevated left ventricular end-diastolic pressure backward on the pulmonary venous circulation and an active vasoreactive process of vasoconstriction and PA remodeling. Pathology studies have shown remodeling changes in the elastic fibers of the pulmonary arterial wall, intimal fibrosis, and medial hypertrophy of pulmonary muscular arteries, with changes that are similar to or greater than those seen in idiopathic PAH. - See more at: http://www.acc.org/latest-in-cardiology/articles/2015/04/14/15/21/left-heart-disease-check-for-pulmonary-hypertension-practical-approaches-to-the-management-of-pulmonary-hypertension#sthash.aXt4vyUX.dpuf

There was a strong, positive, graded association between PA systolic pressure and subsequent mortality that was independent of age, sex, comorbidities, EF, and diastolic function. The investigators found that PA systolic pressure strongly predicted medium-term risk of death in patients with HF and improved prediction of death and CV death over traditional prognostic factors. Importantly, PH appeared to be not only a marker of worse HF, but also to have direct deleterious effects. - See more at: http://www.acc.org/latest-in-cardiology/articles/2015/04/14/15/21/left-heart-disease-check-for-pulmonary-hypertension-practical-approaches-to-the-management-of-pulmonary-hypertension#sthash.aXt4vyUX.dpuf

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