Page 69 - Assessing right ventricular function and the pulmonary circulation in pulmonary hypertension Onno Anthonius Spruijt

Pre-clinical studies have shown that in PH as compared to controls RV contractility, or Ees, is increased and that RV-A coupling is decreased [6, 47, 48]. β-Adrenergic receptor blockade increases contractility and partially restores Ees/Ea in rats with PH induced by monocrotaline (MCT) [6]. Sildenafil improved RV contractility in rats with mechanical RV pressure overload due to pulmonary artery banding [49]. Similar contractility improving effects of Sildenafil were also suggested in another study on MCT rats using a Langendorf preparation [9]. With the same experimental set-up, this group also showed a decrease in RV contractility in MCT rats after Bosentan treatment [8]. Despite the preclinical evidence of direct cardiac effects of pulmonary vasodilators, RV contractility and RV-A coupling were never assessed in clinical trials in PAH patients. In contrast to the cited experimental studies, a recent meta-analysis using pump-function graph analyses, suggested that PAH therapies have little or no cardiac specific effects on top of their vasodilating effects [4]. This may not be true for some of the newer drugs, including growth factor receptor inhibitors.
RV function during exercise
During exercise the cardiovascular system is pushed to its upper limits. Holverda et al [50] showed that exercising iPAH patients show no increase in SV and even a decrease in RVEF. This implies that RV failure becomes more manifest during exercise. Although assessing load-dependent parameters of RV function during exercise is challenging, its interest is rising [51]. Load-independent measurements of RV function can also be assessed during exercise using an exercise protocol during RHC [52]. Future studies will have to reveal if RV functional parameters obtained during exercise could be more sensitive to assess RV responses to therapy.
Conclusions
Today, after two decades of treating PH patients with pulmonary vasodilators, a thorough understanding of RV responses to therapy is still lacking. Given the importance of RV function in patient outcome, future studies on new PH therapies should include a comprehensive determination of load-dependent and load-independent effects of treatment on the RV. Serial assessment of RV structure and function should include a combination of RV parameters and should at least include volumetric parameters. PH therapies specifically targeting the RV, e.g. treatment with β-adrenergic receptor blockers, should use load-independent parameters to determine cardiac- specific effects of therapy.
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