Mauro Lo Rito, MD, Tamadhir Gazzaz, MD, Travis J. Wilder, MD, Rachel D

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Pulmonary vein stenosis: Severity and location predict survival after surgical repair Mauro Lo Rito, MD, Tamadhir Gazzaz, MD, Travis J. Wilder, MD, Rachel D. Vanderlaan, MD, PhD, Glen S. Van Arsdell, MD, Osami Honjo, MD, PhD, Shi-Joon Yoo, MD, PhD, Christopher A. Caldarone, MD The Journal of Thoracic and Cardiovascular Surgery Volume 151, Issue 3, Pages 657-666.e2 (March 2016) DOI: 10.1016/j.jtcvs.2015.08.121 Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Scheme of PV cross-sectional measurements (A) and PV stenosis classification (B). A, The scheme illustrates the upstream (red line) and downstream (blue line) where the diameters are measured by CT/MRI. The long and short diameters are used to calculate single PVCSAi at upstream and downstream levels. The sum of all single PVCSAi provides the TCSAi at the upstream region (red dotted line) and downstream region (blue dotted line). B, In the classification based on PVCSAi upstream/downstream ratio, 3 types of PV morphology can be identified. Predominant downstream narrowing with normal/dilated upstream (ratio >1.5), diffuse string-like narrowing (ratio, 0.5-1.5), and predominant upstream narrowing with normal/dilated downstream (ratio <0.5). In case of upstream/downstream ratio between 0.5 and 1.5, the PVCSAi downstream has been used to differentiate between diffuse string-like stenosis and normal vein; a PVCSAi 50 mm2/m2 or less indicates a stenotic PV, whereas a PVCSAi greater than 50 mm2/m2 indicates normal PV. RUPV, Right upper pulmonary vein; LUPV, left upper pulmonary vein; RLPV, right lower pulmonary vein; LLPV, left lower pulmonary vein; PVCSAi, pulmonary vein cross-sectional area indexed to body surface area. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 657-666.e2DOI: (10.1016/j.jtcvs.2015.08.121) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Measured downstream single PVCSAi versus predicted downstream single PVCSAi by clinically assessed stenosis status. The measured downstream single PVCSAi is shown in the x-axis. The predicted downstream single PVCSAi obtained with Sluysmans and Colan's predictive model is shown in the y-axis.18 Each dot represents a single PV with its measured (x-axis) and predicted (y-axis) PVCSAi value. On the basis of clinical assessment, the blue dots represent nonstenotic PVs and the red dots represent stenotic PVs. The vertical reference black line (50 mm2/m2) is the stenosis cut-point value determined for the measured downstream PVCSAi, and the horizontal black line (47 mm2/m2) is the stenosis cut-point value determined for predicted downstream PVCSAi. PVCSAi, Pulmonary vein cross-sectional area indexed to body surface area. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 657-666.e2DOI: (10.1016/j.jtcvs.2015.08.121) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Overall estimated survival after repair of PV stenosis. Overall unadjusted 8-year survival for all 31 patients after surgical repair for PV stenosis. The survival was 75% ± 7%, 69% ± 8% and 64% ± 7% at 1, 3, and 5 years, respectively. By 8 years, survival decreases to 56% ± 9%. Independent of time, there were a total of 11 deaths. Each circle represents a death positioned on the vertical axis by the Kaplan–Meier estimator. Vertical bars are confidence limits equivalent to ± 1 standard error. Solid lines are parametric estimates enclosed within dashed 68% confidence bands equivalent to ± 1 standard error. Numbers in parentheses are the number of patients at risk at each associated time. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 657-666.e2DOI: (10.1016/j.jtcvs.2015.08.121) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 The impact of upstream TCSAi, downstream TCSAi, and number of stenotic/occluded PVs on survival. A, Risk-adjusted nomogram demonstrating the differential impact on survival across the spectrum of upstream and downstream PV dimensions. The estimated 1-year survival is on the vertical axis across the spectrum of upstream TCSAi. Each curve represents the 1-year survival for a hypothetical patient with a given downstream TCSAi dimension. The black curve represents a downstream TCSAi of 50 mm2/m2. The red curve represents a downstream TCSAi of 100 mm2/m2. The yellow curve represents a downstream TCSAi of 150 mm2/m2. The blue curve represents a downstream TCSAi of 200 mm2/m2. The teal curve represents a downstream TCSAi of 250 mm2/m2. The green curve represents a downstream TCSAi of 300 mm2/m2. The values of the upstream TCSAi have been truncated to fit within the range of data for a given downstream TCSAi size. For example, a patient with a downstream TCSAi of 100 mm2/m2 (red curve) could have an upstream TCSAi from 120 to 470 mm2/m2, whereas a patient with a downstream TCSAi of 50 mm2/m2 (black curve) only had an upstream TCSAi between 170 and 270 mm2/m2. B, The estimated 5-year adjusted survival demonstrating the impact of the downstream TCSAi size on survival. The late survival (>1 year) tended to be worse for smaller downstream TCSAi. Each curve represents a hypothetical patient with 2-vessel stenosis and a median upstream TCSAi size of 260 mm2/m2. Each curve represents the estimated survival based on parametric estimates stratified by the size of the downstream TCSAI: red curve = 60 mm2/m2; yellow curve = 120 mm2/m2; blue curve = 160 mm2/m2; teal curve = 270 mm2/m2; green curve = 300 mm2/m2. C, The estimated 5-year adjusted survival demonstrating the impact of number total number of stenotic PVs on survival. A greater number of PVs with stenosis results in significantly worse survival. The differences in survival are related predominantly to a poor early survival (<1 year) that results with increased vessel involvement. Each curve represents the estimated survival for a hypothetical patient (based on parametric estimates) stratified by the number of stenotic veins with a median upstream TCSAi size of 260 mm2/m2 and median downstream TCSAi size of 160 mm2/m2: red curve = 4 veins with stenosis; yellow curve = 3 veins with stenosis; blue curve = 2 veins with stenosis; green curve = 1 vein with stenosis. TCSAi, Total pulmonary vein cross-sectional area indexed to body surface area. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 657-666.e2DOI: (10.1016/j.jtcvs.2015.08.121) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Scheme of PV diameters, measurements, and stenosis classification. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 657-666.e2DOI: (10.1016/j.jtcvs.2015.08.121) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions