Page 193 - Assessing right ventricular function and the pulmonary circulation in pulmonary hypertension Onno Anthonius Spruijt

Contractile reserve of patients with scleroderma related pulmonary hypertension and patients with scleroderma and borderline pulmonary hypertension
In chapter 10 we compared the contractile reserve between control subjects and precapillary pulmonary hypertension patients. Whether differences exist between different precapillary pulmonary hypertension subtypes is unknown. In systemic scleroderma related pulmonary hypertension right ventricular contractility and right ventricular – arterial coupling at rest are more severely compromised compared to idiopathic pulmonary hypertension patients [19, 20]. Whether or not differences are even more pronounced during exercise is unknown. As such, it would be interesting to study the contractile reserve in systemic scleroderma patients with borderline pulmonary hypertension.
Effectiveness of inotropic drugs in patients with pulmonary hypertension
Contractility can increase due to ẞ-adrenergic stimulation. Inotropic drugs increase catecholamine release which binds to ẞ-adrenergic receptors subsequently activating sarcomeres, the contractile elements of cardiomyocytes.
The European pulmonary hypertension guideline recommends to treat patients with pulmonary arterial hypertension admitted to the hospital because of right ventricular failure with inotropes, with a preference for dobutamine [21]. However, this recommendation is mostly based on expert opinions rather than clear scientific evidence [22-24].
In the right ventricle of patients with pulmonary hypertension there is a downregulation and desensitization of ẞ-adrenergic receptors [25, 26] and patients with pulmonary hypertension have an impaired exertional contractile reserve [13, 14, 16, 18]. Therefore, it can be questioned whether patients with pulmonary hypertension benefit from inotropic drugs. Decreased contractile reserve measured by TAPSE upon dobutamine infusion has been shown in patients with pulmonary hypertension compared to control subjects [27] as well as in a pulmonary hypertension piglet model [28].
Acosta et al. studied the effects of dobutamine in patients with liver cirrhosis and pulmonary hypertension and showed that load-independent right ventricular contractility could increase upon administration of dobutamine [29]. However, pulmonary hypertension in these patients was relatively mild and therefore we do not know whether these results can be extrapolated to pulmonary hypertension patients with more severely compromised hemodynamics.
Chapter 11
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