Impairment of pulmonary vascular reserve and right ventricular systolic reserve in pulmonary arterial hypertension.
BACKGROUND
Exercise capacity is impaired in pulmonary arterial hypertension (PAH). We hypothesized that cardiovascular reserve abnormalities would be associated with impaired hemodynamic response to pharmacological stress and worse outcome in PAH.


METHODS
Eighteen PAH patients (p) group 1 NYHA class II/III and ten controls underwent simultaneous right cardiac catheterization and intravascular ultrasound at rest and during low dose-dobutamine (10 mcg/kg/min) with trendelenburg (DST). We estimated cardiac output (CO), pulmonary vascular resistance (PVR) and capacitance (PC), and PA elastic modulus (EM). We concomitantly measured tricuspid annular plane systolic excursion (TAPSE), RV myocardial peak systolic velocity (Sm) and isovolumic myocardial acceleration (IVA) in PAH patients. Based on the rounded mean + 2 SD of the increase in mPAP in our healthy control group during DST (2.8 + 1.8 mm Hg), PAH p were divided into two groups according to mean PA pressure (mPAP) response during DST, 1: ΔmPAP > 5 mm Hg and 2: ΔmPAP ≤ 5 mm Hg. Cardiovascular reserve was estimated as the change (delta, Δ) during DST compared with rest, including ΔmPAP with respect to ΔCO (ΔmPAP/ΔCO). All patients were prospectively followed up for 2 years.


RESULTS
PAH p showed significant lower heart rate and CO increase than controls during DST, with a significant mPAP and pulse PAP increase and higher ΔmPAP/ΔCO (p < 0.05). Neither hemodynamic, IVUS and echocardiographic data were different between both PAH groups at rest. In group 1, DST caused a higher ΔEM, ΔmPAP/ΔCO, ΔPVR, and ΔTAPSE than group 2, with a lower IVA increase and a negative ΔSV (p < 0.05). TAPSE correlated with mPAP and RVP (p < 0.05) and, IVA and Sm correlated with CO (p < 0.05). ΔEM correlated with ΔmPAP and ΔIVA with ΔCO (p < 0.05). There were two deaths/pulmonary transplantations in group 1 and one death in group 2 during the follow-up (p > 0.05).


CONCLUSIONS
Pulmonary vascular reserve and RV systolic reserve are significantly impaired in patients with PAH. The lower recruitable cardiovascular reserve is significantly related to a worse hemodynamic response to DST and it could be associated with a poor clinical outcome.
Enric
E
Domingo
Pathophysiology Department, School of Medicine, Hospital de Clínicas, Universidad de la República, Avda Italia 2870, PC 11600 Montevideo, Uruguay. jgrig@fmed.edu.uy.
Juan C
JC
Grignola
Rio
R
Aguilar
Christian
C
Arredondo
Nadia
N
Bouteldja
Manuel López
ML
Messeguer
Antonio
A
Roman
D000403:Airway Resistance / Q000502:physiology; D006328:Cardiac Catheterization / Q000379:methods*; D016022:Case-Control Studies; D004452:Echocardiography / Q000379:methods; D025401:Echocardiography, Stress / Q000379:methods*; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D005652:Functional Residual Capacity; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D013318:Stroke Volume; D015996:Survival Rate; D018084:Ultrasonography, Interventional / Q000379:methods; D014655:Vascular Resistance / Q000502:physiology; D018497:Ventricular Dysfunction, Right / Q000175:diagnosis* / Q000503:physiopathology