Network Analysis to Risk Stratify Patients With Exercise Intolerance

Author(s):Show less -

Oldham, William M. ^{[1, 2]} ; Oliveira, Rudolf K. F. ^[3] ; Wang, Rui-Sheng ^[1] ; Opotowsky, Alexander R. ^{[4, 5, 6]} ; Rubins, David M. ^[1] ; Hainer, Jon ^{[5, 7]} ; Wertheim, Bradley M. ^{[1, 2]} ; Alba, George A. ^{[5, 8]} ; Choudhary, Gaurav ^{[9, 10]} ; Tornyos, Adrienn ^{[11, 12]} ; MacRae, Calum A. ^{[1, 4]} ; Loscalzo, Joseph ^{[1, 4]} ; Leopold, Jane A. ^{[1, 4]} ; Waxman, Aaron B. ^{[1, 2]} ; Olschewski, Horst ^{[11, 12]} ; Kovacs, Gabor ^{[11, 12]} ; Systrom, David M. ^{[1, 2]} ; Maron, Bradley A. ^{[4, 13]}

Affiliation:Show less -

^[1] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 - USA

^[2] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 - USA

^[3] Fed Univ Sao Paulo UNIFESP, Dept Med, Div Resp Dis, Sao Paulo - Brazil

^[4] Brigham & Womens Hosp, Div Cardiovasc Med, 77 Ave Louis Pasteur, NRB Room 0630-N, Boston, MA 02115 - USA

^[5] Harvard Med Sch, 77 Ave Louis Pasteur, NRB Room 0630-N, Boston, MA 02115 - USA

^[6] Boston Childrens Hosp, Dept Cardiol, Boston, MA - USA

^[7] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 - USA

^[8] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 - USA

^[9] Brown Univ, Providence Vet Affairs Med Ctr, Dept Med, Div Cardiol, Providence, RI 02912 - USA

^[10] Brown Univ, Alpert Med Sch, Providence, RI 02912 - USA

^[11] Med Univ Graz, Dept Pulmonol, Graz - Austria

^[12] Ludwig Boltzmann Inst Lung Vasc Res, Graz - Austria

^[13] Boston VA Healthcare Syst, Dept Cardiol, Boston, MA - USA

• Document type: Journal article
• Source: Circulation Research; v. 122, n. 6, p. 864+, MAR 16 2018.
• Web of Science Citations: 9

Abstract

Rationale: Current methods assessing clinical risk because of exercise intolerance in patients with cardiopulmonary disease rely on a small subset of traditional variables. Alternative strategies incorporating the spectrum of factors underlying prognosis in at-risk patients may be useful clinically, but are lacking. Objective: Use unbiased analyses to identify variables that correspond to clinical risk in patients with exercise intolerance. Methods and Results: Data from 738 consecutive patients referred for invasive cardiopulmonary exercise testing at a single center (2011-2015) were analyzed retrospectively (derivation cohort). A correlation network of invasive cardiopulmonary exercise testing parameters was assembled using vertical bar r vertical bar>0.5. From an exercise network of 39 variables (ie, nodes) and 98 correlations (ie, edges) corresponding to P<9.5e(-46) for each correlation, we focused on a subnetwork containing peak volume of oxygen consumption (pVo(2)) and 9 linked nodes. K-mean clustering based on these 10 variables identified 4 novel patient clusters characterized by significant differences in 44 of 45 exercise measurements (P<0.01). Compared with a probabilistic model, including 23 independent predictors of pVo(2) and pVo(2) itself, the network model was less redundant and identified clusters that were more distinct. Cluster assignment from the network model was predictive of subsequent clinical events. For example, a 4.3-fold (P<0.0001; 95% CI, 2.2-8.1) and 2.8-fold (P=0.0018; 95% CI, 1.5-5.2) increase in hazard for age-and pVo(2)-adjusted all-cause 3-year hospitalization, respectively, were observed between the highest versus lowest risk clusters. Using these data, we developed the first risk-stratification calculator for patients with exercise intolerance. When applying the risk calculator to patients in 2 independent invasive cardiopulmonary exercise testing cohorts (Boston and Graz, Austria), we observed a clinical risk profile that paralleled the derivation cohort. Conclusions: Network analyses were used to identify novel exercise groups and develop a point-of-care risk calculator. These data expand the range of useful clinical variables beyond pVo(2) that predict hospitalization in patients with exercise intolerance. (AU)

• FAPESP's process: 14/12212-5 - Pulmonary hypertension induced by invasive cardiopulmonary exercise testing in patients with fibrotic interstitial lung diseases
• Grantee: Rudolf Krawczenko Feitoza de Oliveira
• Support Opportunities: Scholarships abroad - Research