Alem Mehari1,2, Norris Igbineweka3, Darlene Allen3, Jim Nichols3, Swee Lay Thein3, Nargues A Weir3,4. 1. Sickle Cell Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland alem.mehari@howard.edu. 2. Division of Pulmonary Diseases, Howard University College of Medicine, Washington, District of Columbia; and. 3. Sickle Cell Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. 4. Inova Advanced Lung Disease Program, Falls Church, Virginia.
Abstract
Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated with early mortality. Chronic thromboembolic PH (CTEPH) is an important complication and contributor to PH in SCD but is likely underappreciated. Guidelines recommend ventilation-perfusion (V/Q) scintigraphy as the imaging modality of choice to exclude CTEPH. Data on V/Q scanning are limited in SCD. Our objective was to compare the performance of V/Q scanning with that of CT pulmonary angiography (CTPA) and to report clinical outcomes associated with abnormal V/Q findings. Methods: Laboratory data, echocardiography, 6-min-walk testing, V/Q scanning, CTPA, and right heart catheterization (RHC) were prospectively obtained. High-probability and intermediate-probability V/Q findings were considered to be abnormal. Included for analysis were 142 SCD adults (aged 40.1 ± 13.7 y, 83 women, 87% hemoglobin SS) in a stable state enrolled consecutively between March 13, 2002, and June 8, 2017. Results: V/Q results were abnormal in 65 of 142 patients (45.8%). CTPA was positive for pulmonary embolism in 16 of 60 (26.7%). RHC confirmed PH (mean pulmonary artery pressure ≥ 25 mmHg) in 46 of 64 (71.9%), of whom 34 (73.9%) had abnormal V/Q findings. Among those without PH by RHC (n = 18), 2 of 18 patients had abnormal V/Q findings. Thirty-three patients had a complete dataset (V/Q scanning, CTPA, and RHC); 29 of 33 had abnormal RHC findings, of whom 26 had abnormal V/Q findings, compared with 11 who had abnormal CTPA findings. There was greater concordance between V/Q findings and RHC (κ-value = 0.53; P < 0.001) than between CTPA and RHC (κ-value = 0.13; P = 0.065). The sensitivity and specificity for V/Q scanning was 89.7% and 75.0%, respectively, whereas CTPA had sensitivity of 37.3% and specificity of 100%. Abnormal V/Q finding swere associated with hemodynamic severity (mean pulmonary artery pressure, 35.2 ± 9.6 vs. 26.9 ± 10.5 mm Hg, P = 0.002; transpulmonary gradient, 21.5 ± 9.7 vs. 12.16 ± 11 mmHg, P = 0.005; and pulmonary vascular resistance, 226.5 ± 135 vs. 140.7 ± 123.7 dynes⋅s⋅cm-5, P = 0.013) and exercise capacity (6-min-walk distance, 382.8 ± 122.3 vs. 442.3 ± 110.6 m, P < 0.010). Thirty-four deaths were observed over 15 y. All-cause mortality was higher in the abnormal-V/Q group (21 [61.8%]) than in the normal-V/Q group (13 [38.2%]) (log-rank test, P = 0.006; hazard ratio, 2.54). Conclusion: V/Q scanning is superior to CTPA in detecting thrombotic events in SCD. Abnormal V/Q findings are associated with PH, worse hemodynamics, lower functional capacity, and higher mortality. Despite high sensitivity in detecting CTEPH, V/Q scanning is underutilized. We recommend the use of V/Q scanning in the evaluation of dyspnea in adult SCD patients given the important implications toward management.
Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated with early mortality. Chronic thromboembolic PH (CTEPH) is an important complication and contributor to PH in SCD but is likely underappreciated. Guidelines recommend ventilation-perfusion (V/Q) scintigraphy as the imaging modality of choice to exclude CTEPH. Data on V/Q scanning are limited in SCD. Our objective was to compare the performance of V/Q scanning with that of CT pulmonary angiography (CTPA) and to report clinical outcomes associated with abnormal V/Q findings. Methods: Laboratory data, echocardiography, 6-min-walk testing, V/Q scanning, CTPA, and right heart catheterization (RHC) were prospectively obtained. High-probability and intermediate-probability V/Q findings were considered to be abnormal. Included for analysis were 142 SCD adults (aged 40.1 ± 13.7 y, 83 women, 87% hemoglobin SS) in a stable state enrolled consecutively between March 13, 2002, and June 8, 2017. Results: V/Q results were abnormal in 65 of 142 patients (45.8%). CTPA was positive for pulmonary embolism in 16 of 60 (26.7%). RHC confirmed PH (mean pulmonary artery pressure ≥ 25 mmHg) in 46 of 64 (71.9%), of whom 34 (73.9%) had abnormal V/Q findings. Among those without PH by RHC (n = 18), 2 of 18 patients had abnormal V/Q findings. Thirty-three patients had a complete dataset (V/Q scanning, CTPA, and RHC); 29 of 33 had abnormal RHC findings, of whom 26 had abnormal V/Q findings, compared with 11 who had abnormal CTPA findings. There was greater concordance between V/Q findings and RHC (κ-value = 0.53; P < 0.001) than between CTPA and RHC (κ-value = 0.13; P = 0.065). The sensitivity and specificity for V/Q scanning was 89.7% and 75.0%, respectively, whereas CTPA had sensitivity of 37.3% and specificity of 100%. Abnormal V/Q finding swere associated with hemodynamic severity (mean pulmonary artery pressure, 35.2 ± 9.6 vs. 26.9 ± 10.5 mm Hg, P = 0.002; transpulmonary gradient, 21.5 ± 9.7 vs. 12.16 ± 11 mmHg, P = 0.005; and pulmonary vascular resistance, 226.5 ± 135 vs. 140.7 ± 123.7 dynes⋅s⋅cm-5, P = 0.013) and exercise capacity (6-min-walk distance, 382.8 ± 122.3 vs. 442.3 ± 110.6 m, P < 0.010). Thirty-four deaths were observed over 15 y. All-cause mortality was higher in the abnormal-V/Q group (21 [61.8%]) than in the normal-V/Q group (13 [38.2%]) (log-rank test, P = 0.006; hazard ratio, 2.54). Conclusion: V/Q scanning is superior to CTPA in detecting thrombotic events in SCD. Abnormal V/Q findings are associated with PH, worse hemodynamics, lower functional capacity, and higher mortality. Despite high sensitivity in detecting CTEPH, V/Q scanning is underutilized. We recommend the use of V/Q scanning in the evaluation of dyspnea in adult SCDpatients given the important implications toward management.
Authors: Alem Mehari; Shoaib Alam; Xin Tian; Michael J Cuttica; Christopher F Barnett; George Miles; Dihua Xu; Catherine Seamon; Patricia Adams-Graves; Oswaldo L Castro; Caterina P Minniti; Vandana Sachdev; James G Taylor; Gregory J Kato; Roberto F Machado Journal: Am J Respir Crit Care Med Date: 2013-04-15 Impact factor: 21.405
Authors: Elizabeth S Klings; Roberto F Machado; Robyn J Barst; Claudia R Morris; Kamal K Mubarak; Victor R Gordeuk; Gregory J Kato; Kenneth I Ataga; J Simon Gibbs; Oswaldo Castro; Erika B Rosenzweig; Namita Sood; Lewis Hsu; Kevin C Wilson; Marilyn J Telen; Laura M Decastro; Lakshmanan Krishnamurti; Martin H Steinberg; David B Badesch; Mark T Gladwin Journal: Am J Respir Crit Care Med Date: 2014-03-15 Impact factor: 21.405
Authors: Nick H Kim; Marion Delcroix; David P Jenkins; Richard Channick; Philippe Dartevelle; Pavel Jansa; Irene Lang; Michael M Madani; Hitoshi Ogino; Vittorio Pengo; Eckhard Mayer Journal: J Am Coll Cardiol Date: 2013-12-24 Impact factor: 24.094
Authors: Gerald Simonneau; Michael A Gatzoulis; Ian Adatia; David Celermajer; Chris Denton; Ardeschir Ghofrani; Miguel Angel Gomez Sanchez; R Krishna Kumar; Michael Landzberg; Roberto F Machado; Horst Olschewski; Ivan M Robbins; Rogiero Souza Journal: J Am Coll Cardiol Date: 2013-12-24 Impact factor: 24.094
Authors: Victor R Gordeuk; Vandana Sachdev; James G Taylor; Mark T Gladwin; Gregory Kato; Oswaldo L Castro Journal: Am J Hematol Date: 2008-01 Impact factor: 10.047
Authors: Salam Alkindi; Anwaar R Al-Ghadani; Samah R Al-Zeheimi; Said Y Alkindi; Naglaa Fawaz; Samir K Ballas; Anil V Pathare Journal: J Int Med Res Date: 2021-12 Impact factor: 1.671