Hmeedan, A

Abstract Rationale Chronic thromboembolic disease (CTED), which is the result of persistent pulmonary vascular obstruction despite 3 months of anticoagulation, can present with significant functional limitations and exercise intolerance despite normal resting hemodynamics. These patients may experience functional impairment due to exercise-induced pulmonary hypertension, impaired stroke volume augmentation with exercise, ventilatory inefficiency, and/or preload insufficiency. Such exercise-induced pathophysiological abnormalities can significantly impair quality of life and contribute to poor long-term outcomes. Although balloon pulmonary angioplasty (BPA) has shown benefit in patients with chronic thromboembolic pulmonary hypertension (CTEPH), its role in CTED patients with normal resting hemodynamics remains uncertain. This systematic review and meta-analysis evaluated the efficacy of BPA in this population. Methods A systematic search of PubMed, Cochrane, Embase, and Scopus was performed from inception through March 1, 2025. A total of 763 studies were screened, of which 42 full-text articles were assessed: six met the inclusion criteria (four retrospective, two prospective), comprising 98 patients. Results Across the included studies, baseline mean values were 20.81 +/- 3.62 mmHg for mean pulmonary arterial pressure (mPAP), 3.49 +/- 1.42 Wood units for pulmonary vascular resistance (PVR), and 405.72 +/- 108.40 m for the 6-minute walk distance (6MWD). Balloon Pulmonary Angioplasty (BPA) was consistently associated with significant improvements in hemodynamic and functional outcomes; BPA reduced mPAP by 3.40 mmHg and PVR by 0.90 WU, while increasing 6MWD by 31.90 m. These changes were also statistically robust across studies, with pooled standardized mean changes (SMC) of -0.88 for mPAP (95% CI, -1.10 to -0.67; P < .05), -0.68 for PVR (95% CI, -0.87 to -0.49; P < .05), and 0.29 for 6MWD (95% CI, 0.13 to 0.45; P < .05). Study-level effect sizes for 6MWD ranged from 0.19 to 0.54 (Figure 1A). Functional improvements were further demonstrated by shifts in NYHA class distribution (Figure 1B). Conclusion BPA was associated with meaningful reductions in mPAP and PVR and significant improvements in functional capacity among patients with CTED. These results indicate that BPA could be an effective treatment for certain patients with CTED, though more research is necessary. This abstract is funded by: None

Abstract Rationale Chronic thromboembolic disease (CTED) is characterized by persistent pulmonary vascular obstruction due to unresolved thromboemboli despite at least three months of anticoagulation. Although resting hemodynamics often remain normal, affected patients frequently develop functional limitation due to exercise-induced pulmonary hypertension, ventilatory inefficiency, limited stroke volume augmentation, or preload insufficiency. Such exercise-induced pathophysiological dysregulation can significantly impair quality of life and contribute to poor long-term outcomes. Pulmonary endarterectomy (PEA) is an established treatment for Chronic Thromboembolic Pulmonary Hypertension (CTEPH), offering significant improvements in hemodynamics and survival. Its role in CTED, however, remains unclear. While CTED has traditionally been managed with anticoagulation and supportive therapy, emerging evidence suggests PEA may provide symptomatic and functional benefit in selected CTED patients. Given the ongoing uncertainty regarding the role of PEA in CTED, we performed a systematic review and meta-analysis to define its safety profile and clinical efficacy in this patient subset. Methods A systematic search of PubMed, Cochrane, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar was conducted from database inception to March 1, 2025. Of 2,244 records screened, 34 full-text articles were assessed, and seven met the inclusion criteria. Results Across the included studies, the pooled baseline mean values were 20.48 ± 3.03 mm Hg for mean pulmonary arterial pressure (mPAP), 2.83 ± 1.11 Wood units for pulmonary vascular resistance (PVR), and 397 ± 100.08 m for the 6-minute walk distance (6MWD). Pulmonary Endarterectomy (PEA) was consistently associated with significant improvements in hemodynamic and functional outcomes; PEA reduced mPAP by 3.58 mmHg (pooled Standardized Mean Change (SMC)=-1.03; 95% CI, -1.23 to -0.83; P < .05), PVR by 0.86 Woods units (pooled SMC=-0.86; 95% CI, -1.05 to -0.67; P < .05), while, conversely, increased 6MWD by 37.49 m (pooled SMC, 0.49; 95% CI, 0.32 to 0.67; P < .05). Study-level effect sizes for 6MWD ranged from 0.21 to 1.47 (Figure 1A). This clinical improvement is further reflected in the enhancement of the NYHA functional class, as illustrated in Figure 1B. Conclusion PEA was associated with significant reductions in mPAP and PVR, as well as a considerable improvement in functional capacity in patients with CTED, with robust results across multiple tests for bias, influence, and sensitivity analyses. These findings support PEA as a viable therapeutic option for selected patients with CTED, although further research is warranted. This abstract is funded by: None

Abstract Background Sulfhemoglobinemia is a rare but potentially life-threatening dyshemoglobinemia resulting from the irreversible incorporation of sulfur into the heme moiety, producing hemoglobin species incapable of oxygen transport. Its clinical presentation often mimics methemoglobinemia, with cyanosis and oxygen saturation (SpO2) readings discordant from arterial partial pressure of oxygen (PaO2). Phenazopyridine, an over-the-counter urinary analgesic, has been implicated as a rare cause, in 3 previously documented cases. Prompt recognition is essential to avoid inappropriate therapy, particularly methylene blue, which can precipitate hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Case Presentation A 71-year-old man with Parkinson’s disease, Crohn’s disease, and chronic anemia presented with unexplained cyanosis and SpO2 readings in the 70-80% range, despite a normal PaO2 of 180 mmHg and absence of respiratory symptoms. He had self-initiated phenazopyridine for dysuria three days prior. CT angiography of the chest and echocardiography with bubble study were unremarkable. Attempts to quantify methemoglobin and carboxyhemoglobin were unsuccessful due to analyzer errors. Laboratory evaluation revealed acute anemia (hemoglobin 5.7 g/dL), indirect hyperbilirubinemia, and low haptoglobin consistent with hemolysis. He was managed supportively with high-flow oxygen, and transfusion of two packed red blood cell units. Although initial G6PD levels were normal, testing during hemolysis can yield false negatives. Given this and the risk of methylene blue-induced oxidative stress, conservative management with ascorbic acid was chosen. The patient’s SpO2 improved gradually, and he was discharged on hospital day three. Send-out tests later confirmed sulfhemoglobinemia (1.1%), elevated cytochrome b5 reductase activity, and normal methemoglobin. Discussion This case underscores the diagnostic and therapeutic challenge of differentiating sulfhemoglobinemia from methemoglobinemia. Both disorders produce functional hypoxia with SpO2-PaO2 dissociation, but sulfhemoglobin cannot revert to hemoglobin and requires erythrocyte turnover for resolution. While methylene blue is the standard therapy for methemoglobinemia, it is ineffective for sulfhemoglobinemia and contraindicated in G6PD deficiency. In our patient, supportive care and transfusion facilitated recovery. Using the Naranjo Adverse Drug Reaction Probability Scale, the causality score was 7, indicating a highly probable relationship between phenazopyridine exposure and sulfhemoglobinemia. A high index of suspicion for G6PD deficiency as well as dyshemoglobinemia with a multidisciplinary collaboration are essential for diagnosis and management of unexplained cyanosis. This abstract is funded by: None