Identification of whole-genome mutations and structural variations of bile cell-free DNA in cholangiocarcinoma.

Bile cell-free DNA (cfDNA) has been reported as a promising liquid biopsy tool for cholangiocarcinoma (CCA), however, the whole-genome mutation landscape and structural variants (SVs) of bile cfDNA remains unknown. Here we performed whole-genome sequencing on bile cfDNA and analyzed the correlation between mutation characteristics of bile cfDNA and clinical prognosis. TP53 and KRAS were the most frequently mutated genes, and the RTK/RAS, homologous recombination (HR), and HIPPO were top three pathways containing most gene mutations. Ten overlapping putative driver genes were found in bile cfDNA and tumor tissue. SVs such as chromothripsis and kataegis were identified. Moreover, the hazard ratio of HR pathway mutations were 15.77 (95% CI: 1.571-158.4), patients with HR pathway mutations in bile cfDNA exhibited poorer overall survival (P = 0.0049). Our study suggests that bile cfDNA contains genome mutations and SVs, and HR pathway mutations in bile cfDNA can predict poor outcomes of CCA patients.

Effects of malnutrition on disease severity and adverse outcomes in idiopathic pulmonary arterial hypertension: a retrospective cohort study.

BACKGROUND: Malnutrition is common in patients with chronic cardiovascular disease and is associated with significantly higher all-cause mortality. Approximately one-third of patients with heart failure are malnourished. However, the relationship between malnutrition and idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to clarify the prognostic value of malnutrition in patients with IPAH. METHODS: A total of 432 consecutive participants with IPAH were included in this study between March 2013 and August 2021. Three common malnutrition assessment tools, including the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were used to evaluate the nutritional status of patients with IPAH. The relationships between the malnutrition tools and long-term adverse outcomes were determined using restricted cubic splines and multivariate Cox regression models. RESULTS: During a mean follow-up of 3.1 years, 158 participants experienced clinical worsening or all-cause death. Patients were stratified into the low-, intermediate- and high-risk groups based on the European Society of Cardiology (ESC) risk stratification, and the PNI (55.9 ± 5.7 vs. 54.4 ± 7.2 vs. 51.1 ± 7.1, P = 0.005) and CONUT score (2.1 ± 0.9 vs. 2.5 ± 1.2 vs. 3.3 ± 1.1, P < 0.001) identified these patient groups better than the GNRI. All three malnutrition tools were associated with well-validated variables that reflected IPAH severity, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide level. The CONUT score exhibited better predictive ability than both the GNRI (ΔAUC = 0.059, P < 0.001) and PNI (ΔAUC = 0.095, P < 0.001) for adverse outcomes and significantly improved reclassification and discrimination beyond the ESC risk score. Multivariable Cox regression analysis indicated that only the CONUT score (hazard ratio = 1.363, 95% confidence interval 1.147, 1.619 per 1.0-standard deviation increment, P < 0.001) independently predicted adverse outcomes. CONCLUSIONS: The malnutrition status was associated with disease severity in patients with IPAH. The CONUT score provided additional information regarding the risk of clinically worsening events, making it a meaningful risk stratification tool for these patients.

Usefulness of risk assessment tools in predicting hemodynamic outcome after balloon pulmonary angioplasty: a comparative analysis.

OBJECTIVES: Several parameters of widely used risk assessment tools for pulmonary arterial hypertension (PAH) have been linked to hemodynamic outcomes of balloon pulmonary angioplasty (BPA). Therefore, we aimed to determine whether these risk assessment tools could be used to predict hemodynamic outcomes following BPA. METHODS: In this retrospective study, we included 139 patients with chronic thromboembolic pulmonary hypertension who had undergone BPA at Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China). We compared the accuracies of seven well-validated risk assessment tools for predicting hemodynamic outcomes following BPA. A favorable hemodynamic outcome was defined as a mean pulmonary arterial pressure < 30 mmHg at follow-up. RESULTS: The baseline risk profiles varied significantly among the risk assessment tools. The US Registry to Evaluate Early and Long-Term PAH Disease Management risk scales and the French risk assessment tools rated most patients as high-risk, while the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) series and laboratory examination-based risk scales categorized most patients as having intermediate-risk profile. COMPERA 2.0 (4-strata) exhibited the highest predictive power among all risk stratifications. Noninvasive risk stratification (COMPERA 2.0 [3-strata]) showed a comparable predictive ability to that of invasive risk stratification (COMPERA 1.0) (area under the curve 0.649 vs. 0.648). Moreover, incorporating diffusing capacity of the lungs for carbon monoxide and tricuspid regurgitation velocity into COMPERA 2.0 (4-strata) further enhanced its predictive power (net reclassification index 0.153, 95% confidence interval 0.009-0.298, p = 0.038). Additionally, this refined COMPERA version had a high calibration accuracy (slope 0.96). CONCLUSION: Although the risk strata distribution varied among different risk assessment tools, the proportion of patients achieving favorable hemodynamics decreased with the escalation of risk stratification in most models. The well-validated risk assessment tools for PAH could also predict hemodynamic outcomes following BPA, and the refined COMPERA 2.0 model exhibited the highest predictive ability among these. Applying risk assessment tools before BPA can facilitate early identification of patients in need of closer monitoring and more intensive interventions, contributing to a better prognosis after BPA.

Association of non-insulin-based insulin resistance indices with disease severity and adverse outcome in idiopathic pulmonary arterial hypertension: a multi-center cohort study.

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.

Blood urea nitrogen to serum albumin ratio as a new indicator of disease severity and prognosis in idiopathic pulmonary artery hypertension.

BACKGROUND: Emerging evidence has shown that the blood urea nitrogen to serum albumin ratio (BAR) is associated with the severity and prognosis of heart failure. However, its role in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study investigated the associations between BAR and functional status, echocardiographic findings, hemodynamics, and long-term outcomes among patients with IPAH. METHODS: This study included consecutive patients who underwent right heart catheterization (RHC) and were diagnosed with IPAH between January 2013 and January 2018 at Fuwai Hospital. The primary outcome was the worsening of clinical symptoms. Spearman correlation coefficients were used to evaluate the association between the BAR and established markers of IPAH severity. Receiver operating characteristic (ROC) curve analysis was used to determine BAR's optimal cut-off and predictive performance. Kaplan-Meier analysis and Cox proportional hazard models assessed the relationship between BAR and clinical worsening. RESULTS: A total of 340 patients with IPAH were included in this study. BAR correlated with well-validated variables that reflected the severity of IPAH, such as World Health Organization functional class, 6-min walk distance, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, mixed venous oxygen saturation, and cardiac index. Kaplan-Meier curves indicated that patients with BAR＞3.80 had a significantly higher clinical worsening rate (log-rank test, P < 0.001) than those with BAR≤3.80. Multivariate Cox analysis showed that BAR could independently predict clinical worsening [hazard ratio(HR):2.642, 95 % confidence interval (CI):1.659-4.208, P < 0.001]. In addition, BAR provided additional predictive value for the European Society of Cardiology (ESC)/European Respiratory Society (ERS) risk assessment score. CONCLUSIONS: BAR reflects disease severity and is independently associated with the prognosis of patients with IPAH.

Causal impact of gut microbiota and associated metabolites on pulmonary arterial hypertension: a bidirectional Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. METHODS: Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. RESULTS: Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. CONCLUSIONS: Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

Tumor biomarkers in evaluating the severity and prognosis of idiopathic pulmonary arterial hypertension: A comprehensive analysis.

Inflammation contributes to development of idiopathic pulmonary arterial hypertension (IPAH), and tumor biomarkers can reflect inflammatory and immune status. We aimed to determine the value of tumor biomarkers in IPAH comprehensively. We enrolled 315 patients with IPAH retrospectively. Tumor biomarkers were correlated with established indicators of pulmonary hypertension severity. Multivariable Cox regression found that AFP (hazard ratio [HR]: 1.587, 95% confidence interval [CI]: 1.014-2.482, p = 0.043) and CA125 (HR: 2.018, 95% CI: 1.163-3.504, p = 0.013) could independently predict prognosis of IPAH. The changes of AFP over time were associated with prognosis of patients, each 1 ng/mL increase in AFP was associated with 5.4% increased risk of clinical worsening (HR: 1.054, 95% CI: 1.001-1.110, p = 0.046), enabling detection of disease progression. Moreover, beyond well-validated PH biomarkers, CA125 was still of prognostic value in the low-risk patients (HR: 1.014, 95% CI: 1.004-1.024, p = 0.004), allowing for more accurate risk stratification and prediction of disease outcomes. AFP and CA125 can serve for prognosis prediction, risk stratification, and dynamic monitor in patients with IPAH.

Optimal short-term outcomes in balloon pulmonary angioplasty: the minimum frequency of three sessions annually.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is typically performed in a sequential manner. OBJECTIVES: This study aimed to determine the lowest frequency of BPA for patients who could not reach treatment goals in a short period. DESIGN: Retrospective cohort. METHODS: We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of performed BPA sessions or treated pulmonary vessels or the ratio of the number of treated pulmonary vessels/the number of baseline lesions (T/P) prior to the initial occurrence of clinical outcome or censored date, we divided patients into different groups. The principal outcome was clinical worsening. RESULTS: After stratifying patients by the number of performed BPA sessions, most baseline parameters were comparable among groups. During follow-up, 31 (16.7%) of 186 patients experienced clinical worsening. The 6-month cumulative clinical worsening-free survival rates of ⩾2 performed sessions group were significantly higher than that of 1 performed session group. The 12-month cumulative rates of clinical worsening-free survival exhibited a declining pattern in the subsequent sequence: ⩾3, 2, and 1 performed BPA sessions, and this trend persisted when follow-up time exceeded 12 months. The 6-, 12-, and 24-month cumulative clinical worsening-free survival rates were comparable between patients with 3 and ⩾4 performed BPA sessions. Similar results were also observed when stratifying patients by the accumulative number of treated pulmonary vessels (⩽8, 9-16, ⩾17) and T/P (⩽0.789, 0.790-1.263, ⩾1.264). CONCLUSION: To achieve optimal short-term outcomes, patients might need to undergo ⩾2 BPA sessions or have ⩾9 pulmonary vessels treated or have T/P ⩾0.790 within 6 months, and undergo ⩾3 BPA sessions or have ⩾17 pulmonary vessels treated or have T/P ⩾1.264 within 12 months.

The least number of BPA session to reach a favorable outcomeWhy was the study done? Balloon pulmonary angioplasty (BPA) has been recommended for patients with chronic thromboembolic pulmonary hypertension, which can significantly improve patients' hemodynamics. However, BPA is typically performed in a stepwise manner, and the duration from the initial session to the final session could extend over a year. If patients could not quickly undergo adequate number of BPA sessions and reach hemodynamic target due to various reasons, what is the best frequency of BPA for them? What did the researchers do? We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of BPA sessions, we divided patients into different groups to identify the best frequency of BPA to improve prognosis. What did the researchers find? Patients who received at least two BPA sessions within six months had significantly better prognosis than those with one BPA session. Patients who received at least three BPA sessions within a year had significantly better prognosis than those with two BPA sessions. What do the findings mean? To achieve optimal short-term outcome, patients might need to undergo at least two BPA sessions within six months, and undergo at least three BPA sessions within a year.

Role of the Systemic Inflammatory Response Index in Predicting Disease Severity and Prognosis in Idiopathic Pulmonary Arterial Hypertension.

Introduction: Mounting evidence indicates a possible connection between the systemic inflammatory response index (SIRI) and the prognosis of heart failure, but its role in idiopathic pulmonary arterial hypertension (IPAH) is not well understood. This study aimed to investigate the relationship between SIRI and variables such as functional ability, echocardiography results, hemodynamic measurements, and long-term outcomes in patients with IPAH. Methods: The study included 426 consecutive IPAH patients who underwent right heart catheterization at Fuwai Hospital from January 2013 to December 2020. SIRI was calculated using composite inflammation indicators from routine blood tests. The main outcome measure was clinical deterioration. Spearman correlation coefficients were used to assess associations between SIRI and indicators of IPAH severity. Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal SIRI threshold and predictive ability. Kaplan-Meier analysis and Cox proportional hazard models were used to examine the relationship between SIRI and clinical deterioration. Results: SIRI showed positive associations with indicators such as N-terminal pro-brain natriuretic peptide, right ventricular end-diastolic diameter, pericardial effusion, mean pulmonary arterial pressure, and pulmonary vascular resistance. Conversely, SIRI had inverse relationships with 6-minute walking distance and left ventricular end-diastolic diameter. Kaplan-Meier curves revealed a significantly higher rate of clinical deterioration in individuals with SIRI > 0.741 compared to those with SIRI ≤ 0.741 (P < 0.001). Adjusted Cox analysis showed SIRI remained an independent predictor of clinical worsening (hazard ratio 1.366, 95% confidence interval 1.073-1.738, P = 0.011). ROC analysis demonstrated SIRI provided additional predictive value beyond the risk assessment score of the European Society of Cardiology/European Respiratory Society. Discussion: In summary, SIRI could predict the severity and prognosis of IPAH independently. It was associated with various indicators of IPAH severity and was a significant predictor of clinical deterioration. SIRI also offered additional predictive value beyond existing risk assessment scores.

Sleep-disordered breathing patterns and prognosis in pulmonary arterial hypertension: A cluster analysis of nocturnal cardiorespiratory signals.

BACKGROUND: Sleep-disordered breathing (SDB) is common among pulmonary arterial hypertension (PAH) patients and has been associated with unfavorable outcomes. This study aims to cluster overnight cardiorespiratory signals to investigate PAH phenotypes and examining their prognostic implications. METHODS: In this retrospective cohort study, we recruited consecutive PAH patients who underwent right heart catheterization and nocturnal cardiorespiratory polygraphy to evaluate SDB. Cluster analysis was employed to classify patients based on their SDB patterns. Cox regression analysis and Kaplan-Meier curves were utilized to assess the association between cluster membership and clinical outcomes. Logistic regression was used to identify risk factors associated with the cluster at higher risk of adverse outcomes. RESULTS: The study comprised 386 PAH patients, with a mean age of 44.7 ± 17.0 years, of which 46.6 % were male. Three distinct clusters of PAH patients were identified: Cluster 1 (N = 182) presented with minimal SDB, Cluster 2 (N = 125) displayed obstructive sleep apnea (OSA) without significant hypoxemia, and Cluster 3 (N = 79) exhibited predominantly severe hypoxemic burden along with comorbid OSA. Notably, patients in Cluster 3 had an independent association with an increased risk of clinical worsening (hazard ratio 1.96, 95 % confidence interval [CI] 1.08-3.56, P = 0.027) compared to those in Clusters 1, even after adjusting for common confounders. The rate of clinical worsening for PAH-related events and mortality was higher in Cluster 3 than in Clusters 1 and 2 (26.6 % vs. 12.6 % and 19.2 %, respectively, log-rank P = 0.024). Moreover, the left ventricular mass index was identified as an independent risk factor for Cluster 3 (odds ratios 1.01, 95 % CI 1.00-1.02, P = 0.004). CONCLUSIONS: Patients with PAH who have nocturnal hypoxemia and OSA had worse clinical outcomes compared to those with only minimal SDB. Tailored management strategies that address both PAH and nocturnal hypoxemia may be effective in improving clinical outcomes.

Angiographic classification of total occlusion and its implication on balloon pulmonary angioplasty.

AIMS: Despite refinements in balloon pulmonary angioplasty (BPA), total occlusion remains a challenge in chronic thromboembolic pulmonary hypertension (CTEPH). Owing to their low success and high complication rates, most interventional cardiologists are reluctant to address total occlusion, and there is a paucity of literature on BPA performance in total occlusion. We aimed to classify total occlusion according to morphology and present an illustrative approach for devising a tailored treatment strategy for each distinct type of total occlusion. METHODS AND RESULTS: All patients diagnosed with CTEPH who underwent BPA between May 2018 and May 2022 at Fuwai Hospital in Beijing, China, were included retrospectively. A total of 204 patients with CTEPH who underwent BPA were included in this study. Among these, 38 occluded lesions were addressed in 33 patients. Based on the morphology, we categorized the lesions into three groups: pointed-head, round-head, and orifice occlusions. Pointed-head occlusion could be successfully addressed using soft-tip wire, round-head occlusion warranted hard-tip wire and stronger backup, and orifice occlusion warranted the strongest backup force. The success rates for each group were as follows: pointed-head (95.45%), round-head (46.15%), and orifice occlusion (33.33%), with orifice occlusion having the highest complication rate (50%). The classification of occlusion was associated with BPA success (round-head occlusion vs. pointed-head occlusion, OR 24.500, 95% CI 2.498-240.318, P = 0.006; orifice occlusion vs. pointed-head occlusion, OR 42.000, 95% CI 3.034-581.434, P = 0.005). CONCLUSIONS: Occlusion morphology has a significant impact on BPA success and complication rates. A treatment strategy tailored to each specific occlusive lesion, as outlined in the present study, has the potential to serve as a valuable guide for clinical practitioners.

Development and validation of a nomogram for predicting hemodynamic response to balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Balloon pulmonary angioplasty (BPA) can effectively alleviate pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Identifying predictors of unfavorable hemodynamic response to BPA is essential to guide clinical practice. Therefore, our objective was to construct and validate a nomogram to facilitate clinicians predicting hemodynamic response to BPA. METHODS: Patients with CTEPH and underwent BPA from May 2018 to April 2022 were retrospectively collected. Favorable hemodynamic response to BPA was defined as a mean pulmonary arterial pressure ≤30 mmHg and/or a reduction in pulmonary vascular resistance ≥30 % at follow-up. RESULTS: A total of 155 patients were included. At baseline, patients with favorable hemodynamic response had significantly lower proportion of occlusive lesions (11.11 % vs. 26.32 %, P = 0.017), higher diffusing capacity of the lungs for carbon monoxide (63.77 % ± 14.10 % vs. 59.11 % ± 11.78 %, P = 0.039), and better cardiac morphology than counterparts. LASSO regression and random forest were used to construct prediction models respectively. The LASSO regression model demonstrated better predictive ability and accuracy than the random forest model, as evidenced by higher area under curve (0.745 vs. 0.740) and lower Brier score (0.192 vs. 0.195). A nomogram was constructed based on the LASSO regression model, consisting of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter, number of treated pulmonary vessels and proportion of occlusion lesions. High predictive ability of the LASSO model was preserved in validation (C index 0.744). CONCLUSIONS: The current study constructed a nomogram with high accuracy in predicting BPA hemodynamic outcome, which could facilitate decision-making in clinical practice.

Impact of Obstructive Sleep Apnea on Disease Severity and Adverse Outcomes in Patients with Acute Pulmonary Embolism.

Purpose: Acute pulmonary embolism (PE) poses a life-threatening risk with high mortality rates. While the coexistence of PE and obstructive sleep apnea (OSA) is gaining recognition, its influence on PE severity and prognosis remains uncertain. This study aims to investigate the associations between OSA and disease severity, as well as outcomes, in patients with acute PE. Patients and Methods: We conducted a retrospective cohort study on patients diagnosed with acute PE who had undergone previous cardiorespiratory polygraphy. OSA severity was assessed using the apnea-hypopnea index (AHI) derived from cardiorespiratory polygraphy. The severity of acute PE was evaluated using the simplified Pulmonary Embolism Severity Index (sPESI) score. Logistic regression analysis was performed to investigate the associations between AHI and the risk of belonging to the sPESI≥1 group. Cox regression analysis was used to examine the relationship between AHI and long-term adverse events, defined as a composite of all-cause mortality and non-fatal cardiovascular events. Results: Among 145 acute PE patients (mean age 62.2 years, 49.7% male), 94 (64.8%) had OSA. Patients with OSA had a significantly higher proportion of sPESI≥1 (89.4% vs 68.6%, p=0.002) than non-OSA patients. Each unit increase in AHI was associated with a 15% increased risk of severe PE (sPESI≥1) (odds ratio: 1.15, 95% CI 1.05-1.26, p=0.002) after adjusting for confounders. During a median follow-up of 15.2 months, 27 (18.6%) patients experienced adverse events. Increased AHI independently predicted a higher risk of adverse events (hazard ratio: 1.03, 95% CI: 1.00-1.05, p=0.026), even after adjusting for potential confounders. AHI ≥8 events/h was associated with a significantly higher adjusted hazard ratio of 2.56 (95% CI: 1.15-5.72, p=0.022) for adverse events compared to AHI <8 events. Conclusion: OSA is common in acute PE patients and is linked to increased disease severity and adverse outcomes. Implementing routine OSA screening and management may aid risk stratification and improve outcomes in acute PE patients.

The potential of cystatin C as a predictive biomarker in pulmonary hypertension.

BACKGROUND: Cystatin C is a novel biomarker to identify renal dysfunction and cardiovascular risk. OBJECTIVE: The aim of this study was to investigate the role of cystatin C in non-invasive risk prediction in a large cohort of patients with pre-capillary pulmonary hypertension (PH). METHOD: We retrospectively analyzed pre-capillary PH patients with available cystatin C and hemodynamic data derived from right heart catheterization. RESULTS: A total of 398 consecutive patients with confirmed pre-capillary PH were recruited from Fuwai Hospital between November 2020 and November 2021. Over a median duration of 282 days, 72 (18.1%) of these patients experienced clinical worsening. Cystatin C levels significantly correlated with cardiac index (r = -0.286, P < 0.001), mixed venous oxygen saturation (r = -0.216, P < 0.001), and tricuspid annular plane systolic excursion (r = -0.236, P < 0.001), and high cystatin C levels independently predicted a poor prognosis after adjusting potential confounders in different models (all P < 0.05). A three-group non-invasive risk model was constructed based on the combined assessment of the cystatin C and WHO-FC using dichotomous cut-off value. Those patients with higher cystatin C (≥ 1.0 mg/L) and a worse WHO-FC experienced the highest risk of endpoint occurrence. The predictive capacity of this model was comparable to that of an existing invasive risk stratification model (area under curve: 0.657 vs 0.643, P = 0.619). CONCLUSIONS: Cystatin C levels were associated with disease severity and prognosis in patients with pre-capillary PH. A combination of high cystatin C and advanced WHO-FC identifies patients at particularly high risk of clinical deterioration.

The defense of Shangri-La: Protecting isolated communities by periodic infection screening in the worst future pandemic.

In the worst future pandemic, effective vaccines and medicines could be unavailable for a long time. In such circumstances, it is necessary to evaluate whether a periodic screening can protect isolated communities and critical facilities and avoid a complete shutdown. In this study, we introduced an epidemiological model that included the essential parameters of infection transmission and screening. With varying parameters, we studied the dynamics of viral infection in the isolated communities. In the scenario with a periodic infection screening once per 3 days and a viral basic reproduction number 3.0, >85% of the infection waves have a duration <7 days and the infection size in each of the waves is generally <4 individuals when the efficiency of infection discovery is 0.9 in the screening. When the period of screening was elongated to once per 7 days, the cases of infection dramatically increased to 5 folds of that mentioned previously. Further, with a weak discovery efficiency of 0.7 and the aforementioned low screening frequency, the spread of infection would be out of control. Our study suggests that frequent periodic screening is capable of controlling a future epidemic in isolated communities without other measures.

Angiographic classification of pulmonary vascular lesion in Takayasu arteritis: A cohort study.

BACKGROUND: Percutaneous transluminal pulmonary angioplasty (PTPA) can significantly improve the haemodynamics and prognosis of patients with Takayasu arteritis and pulmonary artery involvement. However, the choice of PTPA is mainly based on clinical experience. We aim to classify pulmonary artery lesions in Takayasu arteritis according to pulmonary angiogram and evaluate the PTPA success rate and technical difficulty of different types of lesions. METHODS: We enrolled consecutive patients diagnosed with Takayasu arteritis and pulmonary artery involvement. Patients who underwent pulmonary angiography were included. RESULTS: A total of 365 pulmonary vascular lesions were observed in 63 patients based on pulmonary angiography. According to morphology, distal blood flow of the lesions and PTPA treatment success rate, we classified the pulmonary arterial lesions into 4 groups: type A, stenosis; type B, dilation; type C, subtotal occlusion; type D, total occlusion. Total occlusion was further subclassified as D1, cone-shape occlusion; D2, pocket-like occlusion; and D3, ostium occlusion. The success rate of PTPA was higher in stenosis and subtotal occlusion, whereas ostium occlusion had the lowest success rate. The 2-year survival rate was 97.3% in patients who underwent PTPA. CONCLUSIONS: The morphology of pulmonary lesions in Takayasu arteritis had a significant impact on the PTPA success rate. The failure rate and technical difficulty of PTPA increased in the following order: stenosis, dilation, subtotal occlusion, and total occlusion. Our classification scheme could guide the performance of PTPA for pulmonary artery lesions in Takayasu arteritis.

The comorbidity burden and disease phenotype in pre-capillary pulmonary hypertension: The contributing role of obstructive sleep apnea.

BACKGROUND: Pre-capillary pulmonary hypertension (PH) with risk factors for left ventricular diastolic dysfunction, described as an atypical phenotype of "mixed" pre- and post-capillary PH, has become a research focus. However, the relationship between obstructive sleep apnea (OSA), a known risk factor for cardiometabolic conditions, and comorbidity burden and disease phenotype in PH remains unclear. OBJECTIVE: This study aimed to investigate the effect of the presence and severity of OSA on the left ventricular function, comorbidity burden and disease phenotype in pre-capillary PH patients. METHODS AND RESULTS: We retrospectively examined 450 consecutive pre-capillary PH patients undergoing cardiorespiratory polygraphy and right heart catheterization between May 2020 to November 2021 at Fuwai Hospital. The prevalence of OSA was 34.2%, and the presence and severity of OSA in pre-capillary PH patients was associated with increased left heart mass index (P < 0.001), pulmonary arterial wedge pressure (P = 0.06) and H2FPEF score (P < 0.001). After adjustment for confounding factors, the severity of OSA measured as apnea-hypopnea index (AHI) was an independent risk factor associated with obesity, systemic hypertension, diabetes mellitus and an atypical phenotype (OR: 1.054, P = 0.004) in pre-capillary PH. A dose-response relationship was also identified between sleep parameters (AHI, oxygen desaturation index, the percentage of sleep time with oxygen saturation<80%) and the number of key comorbidities. Patients with ≥3 comorbidities (atypical phenotype) were older, experienced negative alterations in left ventricular structure and function, and were at a higher risk of OSA. CONCLUSION: OSA is relatively prevalent in pre-capillary PH patients, independently associated with the presence of a variety of comorbidities and the atypical phenotype of PH. These findings highlight the importance of OSA as a modifiable target for optimal treatment in PH with comorbidities.

Implication of prolonged nocturnal hypoxemia and obstructive sleep apnea for pulmonary hemodynamics in patients being evaluated for pulmonary hypertension: a retrospective study.

STUDY OBJECTIVES: The unique pathophysiologic contributions of obstructive sleep apnea (OSA) toward pulmonary hypertension and right ventricular (RV) dysfunction still represent an understudied area. We aimed to investigate the impacts of various respiratory parameters on pulmonary hemodynamics and RV performance in OSA. METHODS: Data of consecutive patients with OSA who completed right heart catheterization for evaluation of pulmonary hemodynamics were retrospectively reviewed and analyzed. Univariable and multivariable regression analyses were used to determine the significant respiratory parameter associated with right heart catheterization metrics. RESULTS: Of 205 patients with OSA (43.4% male), 134 (65.4%) had pulmonary hypertension. Among various sleep parameters, the time percentage spent with SpO2 below 90% (T90) was the sole and the strongest independent factor associated with mean pulmonary artery pressure (mPAP) (ß = 0.467, P < .001), pulmonary vascular resistance (PVR) (ß = 0.433, P < .001), and RV stroke work index (RVSWI) (ß = 0.338, P < .001). For every 5-unit increase in T90, there was approximately 36% greater risk of mPAP ≥ 25 mmHg (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.16-1.59, P < .001), and 45% greater risk of PVR > 3 Woods units (OR 1.45, 95% CI 1.21-1.74, P < .001), respectively. T90 per 5-unit increment was also related to a nearly 1.2-fold higher risk of RVSWI ≥ 12 g/m2/beat (OR 1.19, 95% CI 1.11-1.28, P < .001). These associations remained significant even after multivariable adjustment for confounding factors (all P < .05). CONCLUSIONS: Increased mPAP, PVR, and RVSWI were associated with prolonged T90 in patients with OSA. Assessment of OSA with insights into hypoxemic duration may aid in early recognition of impaired pulmonary hemodynamics and RV dysfunction. CITATION: Huang Z, Duan A, Hu M, et al. Implication of prolonged nocturnal hypoxemia and obstructive sleep apnea for pulmonary hemodynamics in patients being evaluated for pulmonary hypertension: a retrospective study. J Clin Sleep Med. 2023;19(2):213-223.