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Right Ventricular Diastolic Dysfunction and the Acute Effects of Sildenafil in Pulmonary Hypertension Patients^*

^* From the Departments of Pulmonary Diseases (Mr. Gan, Mr. Holverda, and Drs. Boonstra, Postmus, and Vonk-Noordegraaf), Physics and Medical Technology (Dr. Marcus), Physiology (Dr. Paulus), Cardiology (Drs. Marques and Bronzwaer), and Clinical Epidemiology and Biostatistics (Dr. Twisk), Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands.

Correspondence to: Anton Vonk-Noordegraaf, MD, PhD, VU University Medical Center, De Boelelaan 1117 PO Box 7057, 1007 MB Amsterdam, the Netherlands; e-mail: a.vonk{at}vumc.nl

Abstract

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.

Key Words: diastole • pulmonary hypertension • right ventricular function

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