Chest
Volume 132, Issue 1, July 2007, Pages 11-17
Journal home page for Chest

ORIGINAL RESEARCH
PULMONARY VASCULAR DISEASE
Right Ventricular Diastolic Dysfunction and the Acute Effects of Sildenafil in Pulmonary Hypertension Patients

https://doi.org/10.1378/chest.06-1263Get rights and content

Aims:

This study investigated whether right ventricular (RV) diastolic function is impaired in pulmonary hypertension (PH) patients, and whether it is related to RV mass and afterload. In addition, the effects of an acute reduction of RV afterload by the oral intake of sildenafil were studied. Finally, we assessed whether diastolic function is related to cardiac parameters of disease severity.

Methods and results:

Twenty-five PH patients and 11 control subjects were studied. Right-heart catheterization and N-terminal pro-brain natriuretic peptide (NT-proBNP) sampling were performed in patients. MRI measured RV ejection fraction, mass, and diastolic function. Isovolumic relaxation time (IVRT), normalized early peak filling rate (E), atrium-induced peak filling rate (A), and E/A ratio described diastolic function. Compared to control subjects, patients had prolonged mean (± SD) IVRT (133.5 ± 53.2 vs 29.3 ± 20.8 ms, respectively; p < 0.001), decreased E (3.0 ± 1.6 vs 6.4 ± 2.5 s−1, respectively; p < 0.001) and E/A ratio (1.1 ± 0.7 vs 5.3 ± 4.9, respectively; p < 0.001), and increased A (3.0 ± 1.4 vs 1.5 ± 0.9 s−1, respectively; p = 0.001). IVRT was related to RV mass (r25 = 0.56; p = 0.005) and pulmonary vascular resistance (r25 = 0.74; p < 0.0001). Sildenafil therapy reduced RV afterload and improved RV diastolic and systolic function. IVRT was correlated with NT-proBNP level (r = 0.70; p < 0.001), and was inversely related to cardiac index (r = −0.70; p < 0.001) and RV ejection fraction (r = −0.69; p < 0.001).

Conclusion:

In PH patients, RV diastolic dysfunction is related to RV mass and afterload. RV diastolic function improves by reducing afterload. The correlations between diastolic function and prognostic parameters showed that diastolic function is most impaired in patients with severe disease.

Section snippets

Patients

Twenty-five PH patients with normal renal function and 11 nonsmoking, healthy control subjects were studied. Eighteen patients were referred to our center for the initial evaluation of PH, and seven patients were referred for the evaluation of treatment effects (three patients were receiving epoprostenol, and four patients were receiving bosentan). The different etiologies of PH were distributed as follows: idiopathic pulmonary arterial hypertension (PAH) [n = 18]; PAH related to the limited

Results

There was no difference between the PH patients and control subjects with respect to mean age (PH patients, 49.1 ± 15.3 years; control subjects, 46.5 ± 11.4 years; t34 = 0.59 [t test]; p = 0.56) and the proportion of men/women (PH patients, 5/20; control subjects, 3/8; p = 0.41 [Fisher exact test]). Patient characteristics and hemodynamics are summarized in Table 1. The majority of patients were female and in New York Heart Association functional class III. Hemodynamics yielded the

Discussion

This study showed the following: (1) in PH patients, RV diastolic function, quantified by RV IVRT, peak filling rate, and filling pattern, was significantly impaired compared to control subjects; (2) diastolic function was related to RV mass and afterload, and improved by reducing RV afterload; and (3) RV diastolic dysfunction was related to parameters of disease severity.

Conclusion

RV diastolic function is impaired in PH patients, which is related to RV mass and the extent of RV afterload, and improves by reducing RV afterload. The correlations that were found between diastolic function and well-known prognostic parameters in PH patients showed that diastolic function is most impaired in patients with severe disease.

References (27)

  • H Wilkens et al.

    Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension

    Circulation

    (2001)
  • HA Ghofrani et al.

    Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension

    Ann Intern Med

    (2002)
  • JT Marcus et al.

    MRI evaluation of right ventricular pressure overload in chronic obstructive pulmonary disease

    J Magn Reson Imaging

    (1998)
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      Right ventricular diastolic dysfunction determines ventricular performance and patient outcomes for many conditions. Moreover, this dysfunction may precede the apparent systolic dysfunction (Dernellis 2001; Gan et al. 2007; Leeuwenburgh et al. 2002; Rudski et al. 2010). Overall, we believe that our current findings indicate the great clinical implications for this method with respect to the management of PAH patients.

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    Mr. Gan was financially supported by the Netherlands Organisation for Scientific Research (NWO), Mozaiek grant, project No. 017.001.154.

    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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