安辰鸿
中国医学科学院阜外医院 肺血管与血栓一病区
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.
Sleep medicine 2024
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) (β = 0.467, P < .001), pulmonary vascular resistance (PVR) (β = 0.433, P < .001), and RV stroke work index (RVSWI) (β = 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.
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 2023
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.
Sleep medicine 2023
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.
Nature and science of sleep 2023
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.
BMC pulmonary medicine 2023
BACKGROUND:Dysfunction of autonomic nervous system plays an important role in the development of pulmonary hypertension. The present study aimed to investigate the interaction between balloon pulmonary angioplasty (BPA) and cardiac autonomic function by using heart-rate recovery at 1 min (HRR1) after exercise as a surrogate marker.METHODS AND RESULTS:We retrospectively enrolled 89 consecutive patients with inoperable chronic thromboembolic pulmonary hypertension who underwent BPA from May, 2018 to Jan, 2021. According to hemodynamics at follow-up, patients were categorized as BPA responders if they met one or both of the following criteria: (1) mean pulmonary arterial pressure ≤ 30 mmHg and (2) a reduction of pulmonary vascular resistance ≥ 30%. Compared with baseline, HRR1 tended to increase within 7 days after the first BPA session, and this improvement persisted at follow-up. HRR1 at baseline and at follow-up were associated with well-validated markers of CTEPH severity, including N-terminal pro-brain natriuretic peptide, mean pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, the change of HRR1 from baseline to follow-up was also associated with the change of those variables. After adjustment for confounders, baseline HRR1 was still a strong independent predictor of BPA outcome. Receiver operator characteristic curve analysis showed that the cutoff value for HRR1 in predicting BPA outcome was 19 beats.CONCLUSIONS:BPA could significantly improve HRR1, suggesting the alleviation of sympathovagal imbalance. Easily available and non-invasive HRR1 seems to be a useful tool in predicting outcome of BPA and dynamically monitoring the efficacy of BPA.
Frontiers in cardiovascular medicine 2022
Purpose:Patients with pulmonary arterial hypertension (PAH) are at high risk for obstructive sleep apnea (OSA), which may adversely affect pulmonary hemodynamics and long-term prognosis. However, there is no clinical prediction model to evaluate the probability of OSA among patients with PAH. Our study aimed to develop and validate a nomogram for predicting OSA in the setting of PAH.Patients and Methods:From May 2020 to November 2021, we retrospectively analyzed the medical records of 258 patients diagnosed with PAH via right-heart catheterization. All participants underwent overnight cardiorespiratory polygraphy for OSA assessment. General clinical materials and biochemical measurements were collected and compared between PAH patients with or without OSA. Lasso regression was performed to screen potential predictors. Multivariable logistic regression analysis was conducted to establish the nomogram. Concordance index, calibration curve, and decision curve analysis were used to determine the discrimination, calibration, and clinical usefulness of the nomogram.Results:OSA was present in 26.7% of the PAH patients, and the prevalence did not differ significantly between male (29.7%) and female (24.3%) patients. Six variables were selected to construct the nomogram, including age, body mass index, hypertension, uric acid, glycated hemoglobin, and interleukin-6 levels. Based on receiver operating characteristic analysis, the nomogram demonstrated favorable discrimination accuracy with an area under the curve (AUC) of 0.760 for predicting OSA, exhibiting a better predictive value in contrast to ESS (AUC = 0.528) (P < 0.001). Decision curve analysis and clinical impact curve analysis also indicated the clinical utility of the nomogram.Conclusion:By establishing a comprehensive and practical nomogram, we were able to predict the presence of OSA in patients with PAH, which may facilitate the early identification of patients that benefit from further diagnostic confirmation and intervention.
Nature and science of sleep 2022
Aims:Impairment of right ventricle-to-pulmonary artery coupling (RV-PA coupling) is a major determinant of poor prognosis in patients with pulmonary hypertension. This study sought to evaluate the ability of an echo-derived metric of RV-PA coupling, the ratio between tricuspid annular plane systolic excursion (TAPSE), and pulmonary artery systolic pressure (PASP) and to predict adverse clinical outcomes in chronic thromboembolic pulmonary hypertension (CTEPH).Methods and results:A total of 205 consecutive patients with confirmed CTEPH were retrospectively recruited from Fuwai Hospital between February 2016 and November 2020. Baseline echocardiography, right heart catheterization, and cardiopulmonary exercise testing were analyzed. Patients with lower TAPSE/PASP had a significantly compromised echocardiographic and hemodynamic status and exercise capacity at baseline. The TAPSE/PASP ratio correlated significantly with hemodynamic parameters, including pulmonary vascular resistance (r = -0.48, p < 0.001) and pulmonary arterial compliance (r = 0.45, p < 0.001). During a median period of 1-year follow-up, 63 (30.7%) patients experienced clinical worsening. The relationship between TAPSE/PASP and clinical worsening was assessed using different multivariate Cox regression models. After adjustment for a series of previously screened independent predictors, TAPSE/PASP remained significantly associated with outcomes, and the hazard ratio (per standard deviation increase) of the final model was 0.402.Conclusion:In patients with CTEPH, baseline RV-PA coupling measured as the TAPSE/PASP ratio is associated with disease severity and adverse outcomes. A low TAPSE/PASP identifies patients with a high risk of clinical deterioration, and this novel metric could be applicable for risk stratification in CTEPH.
Therapeutic advances in chronic disease 2022
OBJECTIVES:Previous studies demonstrated that connective tissue diseases-associated pulmonary arterial hypertension (CTD-PAH) had a worse prognosis than idiopathic pulmonary arterial hypertension (IPAH), although the former one had better haemodynamic profiles and right heart function. To find potential explanations for this contradictory phenomenon, we compared the exercise pathophysiology of CTD-PAH with that of IPAH using cardiopulmonary exercise testing (CPET).METHODS:Ninety-three CTD-PAH patients were retrospectively enrolled and matched 1:1 with 93 IPAH patients according to age, gender, body mass index, and body surface area. Multiple linear regression analysis was performed to adjust confounding factors.RESULTS:CTD-PAH had higher rest heart rate (HR@Rest) and lower rest oxygen uptake/HR (VO2/HR@Rest) than IPAH. During exercise, the peak power (Power@Peak), VO2@Peak, peak metabolic equivalents (METS@Peak), peak minute ventilation (VE@Peak), peak tidal volume (VT@Peak), HR@Peak, peak systolic blood pressure (SBP@Peak) and peak diastolic blood pressure (DBP@Peak) of CTD-PAH were lower than those of IPAH. After adjustment, CTD-PAH still had lower values of Power@Peak, VO2@Peak, METS@Peak, VT@Peak, VO2/HR@Rest, DBP@Peak and had higher HR@Rest than IPAH.CONCLUSIONS:CTD-PAH had more impaired ventilation, cardiac function and muscular strength (reflected by CPET-derived parameters) than IPAH, in despite of better haemodynamic profiles and comparable heart structure (assessed by echocardiography) and functional status (indicated by World Health Organisation functional class, N-terminal pro-brain natriuretic peptide and six-minute walk distance).
Clinical and experimental rheumatology 2021
Background: Emerging evidence has showed that serum carbohydrate antigen 125 (CA 125) levels are associated with the severity and prognosis of heart failure. However, its role in pulmonary hypertension remains unclear. This study aimed to investigate the clinical, echocardiographic, hemodynamic, and prognostic associations of CA 125 in pulmonary hypertension. Methods and Results: We conducted a retrospective cohort study of all idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients receiving CA 125 measurement in Fuwai Hospital (January 1, 2014-December 31, 2018). The primary end-point was cumulative 1-year clinical worsening-free survival rate. Linear regression was performed to assess the association between CA 125 and clinical, echocardiographic, and hemodynamic parameters. Cox proportional hazards models were used to assess the association between CA 125 and clinical worsening events. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive performance of CA 125. A total of 231 patients were included. After adjustment, CA 125 still positively correlated with World Health Organization functional class, NT-proBNP, right ventricular end-diastolic diameter, pericardial effusion, mean right atrial pressure and pulmonary arterial wedge pressure; negatively correlated with 6-min walk distance, left ventricular end-diastolic diameter, mixed venous oxygen saturation, and cardiac index. After adjustment, CA 125 > 35 U/ml was associated with over 2 folds increased risk of 1-year clinical worsening. Further, ROC analysis showed that CA 125 provided additional predictive value in addition to the established pulmonary hypertension biomarker NT-proBNP. Conclusion: CA 125 was associated with functional status, echocardiography, hemodynamics and prognosis of pulmonary hypertension.
Frontiers in cardiovascular medicine 2021
