Residual pulmonary vasodilative reserve predicts outcome in idiopathic pulmonary hypertension

Objective: Idiopathic pulmonary arterial hypertension (IPAH) remains a devastating and incurable, albeit treatable condition. Treatment response is not uniform and parameters that help to anticipate a rather benign or a malignant course of the disease are warranted. Acute pulmonary vasoreactivity testing during right heart catheterisation is recommended to identify a minority of patients with IPAH with sustained response to calcium channel blocker therapy. This study aimed to evaluate the prognostic significance of a residual pulmonary vasodilative reserve in patients with IPAH not meeting current vasoresponder criteria. Design: Observational right heart catheter study in 66 (n=66) patients with IPAH not meeting current vasoresponse criteria. Pulmonary vasodilative reserve was assessed by inhalation of 5 µg iloprost-aerosol. Results: Sixty-six (n=66) of 72 (n=72) patients with IPAH did not meet current definition criteria assessed during vasodilator testing to assess pulmonary vasodilatory reserve. In those, iloprost-aerosol caused a reduction of mean pulmonary artery pressure (Δ pulmonary artery pressure—11.4%; p<0.001) and increased cardiac output (Δ cardiac output +16.7%; p<0.001), resulting in a reduction of pulmonary vascular resistance (Δ pulmonary vascular resistance—25%; p<0.001). The magnitude of this response was pronounced in surviving patients. A pulmonary vascular resistance reduction of ≥30% turned out to predict outcome in patients with IPAH. Conclusions: Residual pulmonary vasodilative reserve during acute vasodilator testing is of prognostic relevance in patients with IPAH not meeting current definitions of acute vasoreactivity. Therefore vasoreactivity testing holds more information than currently used

Residual pulmonary vasodilative reserve predicts outcome in idiopathic pulmonary hypertension

Objective: Idiopathic pulmonary arterial hypertension (IPAH) remains a devastating and incurable, albeit treatable condition. Treatment response is not uniform and parameters that help to anticipate a rather benign or a malignant course of the disease are warranted. Acute pulmonary vasoreactivity testing during right heart catheterisation is recommended to identify a minority of patients with IPAH with sustained response to calcium channel blocker therapy. This study aimed to evaluate the prognostic significance of a residual pulmonary vasodilative reserve in patients with IPAH not meeting current vasoresponder criteria. Design: Observational right heart catheter study in 66 (n=66) patients with IPAH not meeting current vasoresponse criteria. Pulmonary vasodilative reserve was assessed by inhalation of 5 µg iloprost-aerosol. Results: Sixty-six (n=66) of 72 (n=72) patients with IPAH did not meet current definition criteria assessed during vasodilator testing to assess pulmonary vasodilatory reserve. In those, iloprost-aerosol caused a reduction of mean pulmonary artery pressure (Δ pulmonary artery pressure—11.4%; p<0.001) and increased cardiac output (Δ cardiac output +16.7%; p<0.001), resulting in a reduction of pulmonary vascular resistance (Δ pulmonary vascular resistance—25%; p<0.001). The magnitude of this response was pronounced in surviving patients. A pulmonary vascular resistance reduction of ≥30% turned out to predict outcome in patients with IPAH. Conclusions: Residual pulmonary vasodilative reserve during acute vasodilator testing is of prognostic relevance in patients with IPAH not meeting current definitions of acute vasoreactivity. Therefore vasoreactivity testing holds more information than currently used

Self-Report Daily Life Activity as a Prognostic Marker of Idiopathic Pulmonary Fibrosis

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive disease, leading to substantial physical impairment. The distance walked in 6 min (6MWD) is a measure of exercise tolerance and is of prognostic relevance in IPF. While 6MWD is a punctual measurement which may not be representative, self-reported daily life activity may represent the patients' functional capacity more globally even in less severe affected patients. OBJECTIVES We evaluated and characterized a simple classification system based on the patients' self-reported daily activity and analyzed if this would add significantly to the prognostic information of the 6MWD alone in IPF patients. METHODS Daily life activity was assessed in IPF (n = 156) patients with standardized questions and categorized in activity classes (AC I-IV), comprising the less severe impaired in AC I and II. The 6MWD was also assessed. RESULTS ACs were related to the lung functional impairment and inversely correlated to the 6MWD. Thirty-two patients were in AC I/II, 98 in AC III and 26 patients in AC IV. Thirty-seven (23.7%) patients died during a median follow-up of 14.9 months, comprising 1 patient in AC I/II. In addition, a 6MWD \textless470 m predicted mortality. Combining AC I/II and a 6MWD \textgreater470 m identified a subgroup of patients with favorable outcome. CONCLUSIONS AC is a novel scoring system which can easily be obtained and correlates with lung functional and physical impairments as well as mortality. Moreover, AC adds prognostic information to the 6MWD

Sparse Decomposition and Modeling of Anatomical Shape Variation

Recent advances in statistics have spawned powerful methods for regression and data decomposition that promote sparsity, a property that facilitates interpretation of the results. Sparse models use a small subset of the available variables and may perform as well or better than their full counterparts if constructed carefully. In most medical applications, models are required to have both good statistical performance and a relevant clinical interpretation to be of value. Morphometry of the corpus callosum is one illustrative example. This paper presents a method for relating spatial features to clinical outcome data. A set of parsimonious variables is extracted using sparse principal component analysis, producing simple yet characteristic features. The relation of these variables with clinical data is then established using a regression model. The result may be visualized as patterns of anatomical variation related to clinical outcome. In the present application, landmark-based shape data of the corpus callosum is analyzed in relation to age, gender, and clinical tests of walking speed and verbal fluency. To put the data-driven sparse principal component method into perspective, we consider two alternative techniques, one where features are derived using a model-based wavelet approach, and one where the original variables are regressed directly on the outcome

Long-term effects of intravenous iloprost in patients with idiopathic pulmonary arterial hypertension deteriorating on non-parenteral therapy

Background: The majority of patients with idiopathic pulmonary arterial hypertension (IPAH) in functional classes II and III are currently being treated with non-parenteral therapies, including endothelin receptor antagonists (ERA), phosphodiesterase (PDE)-5 inhibitors, inhaled iloprost or combinations of these substances. If these treatments fail, current guidelines recommend the addition of parenteral prostanoid therapy. There is, however, limited evidence for the efficacy of parenteral prostanoids when added to combinations of non-parenteral therapies. Methods: In this retrospective, multicentre study we collected data from consecutive IPAH patients receiving intravenous iloprost in addition to optimized non-parenteral therapy between Jan 2002 and Dec 2009. Analyses included 6 min walk distance (6MWD), functional class, need for transplantation, and survival. Results: During the observation period, 50 patients were treated with intravenous iloprost in addition to non-parenteral therapy; 44% of the patients were on dual combination therapy and 52% on triple combination. Three months after initiation of iloprost, functional class had improved in 24% of the patients and the median 6MWD had increased from 289 m to 298 m (n.s.). During the observation period, 22 patients (44%) died and 14 (28%) underwent lung transplantation. The probabilities of LuTx-free survival at 1, 3 and 5 years following iloprost initiation were 38%, 17% and 17%, respectively. A 6MWD &lt; 300 m and persistent functional class IV at 3 months after initiation of intravenous iloprost were predictors of an adverse outcome. Conclusion: In essence, late initiation of intravenous iloprost in IPAH patients who previously failed to respond to non-parenteral therapies appears to be of limited efficacy in the majority patients. Alternative therapeutic options are currently not available, underlying the need for the development of new drugs