Pulmonary hypertension (PH), a common complication of left heart diseases (LHD), negatively impacts symptoms, exercise capacity, and outcome. Although the true prevalence of PH-LHD is unknown, a subset of patients might present significant PH that cannot be explained by a passive increase in left-sided filling pressures. The term "out-of-proportion" PH has been used to identify that population without a clear definition, which has been found less than ideal and created confusion. We propose a change in terminology and a new definition of PH due to LHD. We suggest to abandon "out-of-proportion" PH and to distinguish "isolated post-capillary PH" from "post-capillary PH with a pre-capillary component" on the basis of the pressure difference between diastolic pulmonary artery pressure and pulmonary artery wedge pressure. Although there is no validated treatment for PH-LHD, we provide insights into management and discuss completed and randomized trials in this condition. Finally, we provide recommendations for future clinical trials to establish safety and efficacy of novel compounds to target this area of unmet medical need.

Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP] <25 mm Hg); COPD/IPF/CPFE with PH (mPAP ≥25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP ≥35 mm Hg or mPAP ≥25 mm Hg with low cardiac index [CI <2.0 l/min/m(2)]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on this severe PH group, and for the time being, these patients should be transferred to expert centers for individualized patient care.

Objective: To determine the prevalence of systemic sclerosis associated pulmonary arterial hypertension (SScPAH), evaluate outcome, and identify predictors of mortality in a large patient cohort. Methods: A prospective four year follow up study of 794 patients (722 from our own unit and 72 referrals). All patients screened for PAH using a combination of echocardiography, lung function testing, and clinical assessment. Patients with suspected raised pulmonary artery systolic pressures of .35 mm Hg, carbon monoxide transfer factor (TLCO) ,50% predicted, or a precipitous fall in TLCO .20% over a one year period with no pulmonary fibrosis, and patients with SSc with breathlessness with no pulmonary fibrosis found were investigated with right heart catheterisation. All patients with SScPAH were treated in accordance with current best practice. Results: The prevalence of PAH was 12% (89/722) by right heart catheter. The survival was 81%, 63%, and 56% at 1, 2, and 3 years from the diagnosis (in 89 patients from our own cohort and 59/72 referrals). Haemodynamic indices of right ventricular failure-raised mRAP (hazard ratio 21), raised mPAP (hazard ratio 20), and low CI (hazard ratio 11) predicted an adverse outcome There was no significant difference in survival between patients with SScPAH with (n = 40) and without (n = 108) pulmonary fibrosis (p = 0.3). Conclusions: The prevalence of SScPAH in this cohort was similar to that of other catheter based studies and lower than that of previous echo based studies. The 148 patients with SScPAH actively treated had comparable outcomes to those of the cohorts with primary pulmonary hypertension. A high mRAP was the strongest haemodynamic predictor of mortality. To improve prognosis, future treatments need to be implemented at an earlier disease stage to prevent right ventricular decompensation.

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Several prognostic variables have previously been identified in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Specific medical conditions have also been associated with the development and prognosis of CTEPH. Using a national registry, the current authors have assessed the prognostic value of a larger number of variables and have also attempted to validate the clinical importance of previously identified aetiological factors.Baseline information for all 469 CTEPH patients diagnosed in the UK pulmonary hypertension service between January 2001 and June 2006 was collected from hospital records.Although univariate analysis confirmed the prognostic importance of pulmonary resistance, in multivariate analysis gas transfer and exercise capacity predicted pulmonary endarterectomy perioperative mortality. Cardiac index and exercise capacity independently predicted outcome in patients with nonoperable disease. Previous splenectomy was noted in 6.7% of patients, being significantly more common in patients with nonoperable than operable disease (13.7 versus 3.6%). Medical risk factors were not found to predict mortality.In a large national cohort, predictors of outcome in patients with both operable and nonoperable chronic thromboembolic pulmonary hypertension have been identified. These may be useful in planning treatment. The aetiological importance of previously identified medical risk factors has been confirmed, although the current authors were unable to validate their prognostic strength.

Objective. To determine whether patients with systemic sclerosis (SSc) and borderline mean pulmonary artery pressure (PAP) at cardiac catheterization are more likely to develop pulmonary hypertension (PH) than those in whom pulmonary pressure is normal.Methods. Patients with SSc in whom PH and significant interstitial lung disease had been excluded at baseline were enrolled in our prospective cohort. Analysis of followup data identified patients who met prespecified criteria prompting repeat catheterization to reassess for possible PH. Using Kaplan-Meier, receiver operating characteristic, and Cox regression methods, we studied the development of PH and death.Results. Of 228 patients in this study, 86 had borderline mean PAP (21-24 mm Hg) at baseline. Following prespecified criteria, 76 patients underwent repeat catheterization, and 29 of these developed PH. Two cases were related to disease of the left side of the heart. The average mean PAP increased from baseline (20.2 mm Hg) to followup (24.3 mm Hg) (P < 0.05 by Student's t-test). Patients with borderline mean PAP were more likely to develop PH than patients with mean PAP <20 mm Hg (P < 0.001 by log rank test, hazard ratio [HR] 3.7). A transpulmonary gradient (TPG) >11 mm Hg at baseline also predicted PH (P < 0.001 by log rank test, HR 7.9). Incident development of pulmonary arterial hypertension (PAH) was not benign, with a mortality of 18% within 3 years.Conclusion. Our findings indicate that borderline mean PAP and an elevated TPG in patients with SSc predict progression to PH. These patients should be monitored closely for the development of PH. Our findings indicate that catheterization data are useful in patients considered at risk of PAH.

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