High Prevalence of Occult Pulmonary Venous Hypertension Revealed by Fluid Challenge in Pulmonary Hypertension

Background— Determining the cause for pulmonary hypertension is difficult in many patients. Pulmonary arterial hypertension (PAH) is differentiated from pulmonary venous hypertension (PVH) by a wedge pressure (PWP) >15 mm Hg in PVH. Patients undergoing right heart catheterization for evaluation of pulmonary hypertension may be dehydrated and have reduced intravascular volume, potentially leading to a falsely low measurement of PWP and an erroneous diagnosis of PAH. We hypothesized that a fluid challenge during right heart catheterization would identify occult pulmonary venous hypertension (OPVH). Methods and Results— We reviewed the results of patients undergoing fluid challenge in our pulmonary hypertension database from 2004 to 2011. Baseline hemodynamics were obtained and repeated after infusion of 0.5 L of normal saline for 5 to 10 minutes. Patients were categorized as OPVH if PWP increased to >15 mm Hg after fluid challenge. Baseline hemodynamics in 207 patients met criteria for PAH. After fluid challenge, 46 patients (22.2%) developed a PWP >15 mm Hg and were reclassified as OPVH. Patients with OPVH had a greater increase in PWP compared with patients with PAH, P<0.001, and their demographics and comorbid illnesses were similar to patients with PVH. There were no adverse events related to fluid challenge. Conclusions— Fluid challenge at the time of right heart catheterization is easily performed, safe, and identifies a large group of patients diagnosed initially with PAH, but for whom OPVH contributes to pulmonary hypertension. These results have implications for therapeutic trials in PAH and support the routine use of fluid challenge during right heart catheterization in patients with risk factors for PVH.

[1]  Yuhui Zhang,et al.  Diastolic pulmonary vascular pressure gradient: a predictor of prognosis in "out-of-proportion" pulmonary hypertension. , 2013, Chest.

[2]  B. Levine,et al.  Hemodynamic Responses to Rapid Saline Loading: The Impact of Age, Sex, and Heart Failure , 2013, Circulation.

[3]  Horst Olschewski,et al.  Updated clinical classification of pulmonary hypertension. , 2009, Journal of the American College of Cardiology.

[4]  M. Hudson,et al.  High prevalence of occult left heart disease in scleroderma-pulmonary hypertension , 2012, European Respiratory Journal.

[5]  Sanjiv J. Shah,et al.  Clinical Characteristics of Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction , 2011, Circulation. Heart failure.

[6]  R. Arena,et al.  Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction: A Target of Phosphodiesterase-5 Inhibition in a 1-Year Study , 2009, Circulation.

[7]  R. Nishimura,et al.  Exercise Hemodynamics Enhance Diagnosis of Early Heart Failure With Preserved Ejection Fraction , 2010, Circulation. Heart failure.

[8]  M. Raza.  Misclassification of Pulmonary Hypertension Due to Reliance on Pulmonary Capillary Wedge Pressure Rather Than Left Ventricular End-Diastolic Pressure , 2010 .

[9]  S. Halpern,et al.  Misclassification of pulmonary hypertension due to reliance on pulmonary capillary wedge pressure rather than left ventricular end-diastolic pressure. , 2009, Chest.

[10]  J. Newman,et al.  Association of the metabolic syndrome with pulmonary venous hypertension. , 2009, Chest.

[11]  A. Torbicki,et al.  Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. , 2008, Journal of the American College of Cardiology.

[12]  R. Zimlichman,,et al.  Clinical and Hemodynamic Effects of Bosentan Dose Optimization in Symptomatic Heart Failure Patients with Severe Systolic Dysfunction, Associated with Secondary Pulmonary Hypertension – A Multi-Center Randomized Study , 2007, Cardiology.

[13]  R. Gerszten,et al.  Sildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension , 2007, Circulation.

[14]  C. O'connor,et al.  Tezosentan in patients with acute heart failure: design of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study (VERITAS). , 2005, American heart journal.

[15]  J. McMurray,et al.  Long-term effects of darusentan on left-ventricular remodelling and clinical outcomes in the EndothelinA Receptor Antagonist Trial in Heart Failure (EARTH): randomised, double-blind, placebo-controlled trial , 2004, The Lancet.

[16]  D. Mccrory,et al.  Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. , 2004, Chest.

[17]  F. Harrell,et al.  A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST). , 1997, American heart journal.

[18]  P. Reddy,et al.  Preoperative pulmonary hemodynamics and early mortality after orthotopic cardiac transplantation: the Pittsburgh experience. , 1993, American heart journal.

[19]  K. Moser,et al.  Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. , 1993, Chest.

[20]  N. Fowler.  Occult Constrictive Pericardial Disease , 1978, Circulation.

[21]  J. Kilman,et al.  Occult Constrictive Pericardial Disease: Diagnosis by Rapid Volume Expansion and Correction by Pericardiectomy , 1977, Circulation.

[22]  C. Lafarge,et al.  The estimation of oxygen consumption. , 1970, Cardiovascular research.