The Usefulness of the TAPSE/sPAP Ratio for Predicting Survival in Medically Treated Chronic Thromboembolic Pulmonary Hypertension.

OBJECTIVE: The ventriculoarterial uncoupling has been linked with unfavorable results as measured noninvasively by tricuspid annular plane systolic excursion divided by systolic pulmonary artery pressure (TAPSE/sPAP). However, its prognostic importance in chronic thromboembolic pulmonary hypertension (CTEPH) is limited. Thus, we determine the effect of the TAPSE/sPAP ratio on outcomes and predictors of all-cause mortality in these patients. METHODS: We analyzed 56 subjects with medically treated CTEPH. Two-dimensional echocardiographic examination and right heart catheterization findings were recorded from the hospital database. Baseline New York Heart Association functional class (NYHA-FC), 6-min walk distance (6MWD), and brain natriuretic peptide (BNP) test results were recorded. RESULTS: The median age was 65.5 years. Over a median follow-up time of 27 months, 29 (51.8%) patients died. BNP values were higher (P = 0.008), 6MWD values were lower (P = 0.004), and NHYA-FC (P = 0.0001) was worse in the non-survivor group. TAPSE (P = 0.0001) and TAPSE/sPAP ratio (P = 0.001) were significantly lower and pulmonary vascular resistance (PVR) was higher in the non-survivor group (P = 0.03). The best cut-off value for the TAPSE/sPAP ratio for predicting mortality was 0.20 mm/mmHg and the survival rates were significantly lower in the TAPSE/sPAP ratio ≤0.20 group (log-rank P = 0.012). 6MWD (P = 0.005), NHYA-FC III-IV (P = 0.0001), TAPSE/sPAP ratio ≤0.20 (P = 0.017), PVR (P = 0.008), and TAPSE/sPAP ratio ≤0.20 combined with NYHA-FC III-IV (P = 0.0001) were significant determinants and TAPSE/sPAP ratio ≤0.20 combined with NYHA-FC III-IV was the only independent predictor of mortality (P = 0.003). CONCLUSION: Medically treated CTEPH patients with a TAPSE/sPAP ratio ≤0.20 had lower survival rates. TAPSE/sPAP ratio≤0.20 combined with NYHA-FC III-IV was the independent predictor of poor prognosis.

Risk prediction in pulmonary hypertension due to chronic heart failure: incremental prognostic value of pulmonary hemodynamics.

BACKGROUND: There is no generally accepted comprehensive risk prediction model cooperating risk factors associated with heart failure and pulmonary hemodynamics for patients with pulmonary hypertension due to left heart disease (PH-LHD). We aimed to explore outcome correlates and evaluate incremental prognostic value of pulmonary hemodynamics for risk prediction in PH-LHD. METHODS: Consecutive patients with chronic heart failure undergoing right heart catheterization were prospectively enrolled. The primary endpoint was all-cause mortality. Individual variable selection was performed by machine learning methods. Cox proportional hazards models were conducted to identify the association between variables and mortality. Incremental value of hemodynamics was evaluated based on the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) scores. RESULTS: A total of 276 PH-LHD patients were enrolled, with a median follow-up time of 34.7 months. By L1-penalized regression model and random forest approach, diastolic pressure gradient (DPG) and mixed venous oxygen saturation (SvO2) were the hemodynamic predictors most strongly associated with mortality (coefficient: 0.0255 and -0.0176, respectively), with consistent significance after adjusted for SHFM [DPG: HR 1.067, 95% CI 1.024-1.113, P = 0.022; SvO2: HR 0.969, 95% CI 0.953-0.985, P = 0.002] or MAGGIC (DPG: HR 1.069, 95% CI 1.026-1.114, P = 0.011; SvO2: HR 0.970, 95% CI 0.954-0.986, P = 0.004) scores. The inclusion of DPG and SvO2 improved risk prediction compared with using SHFM [net classification improvement (NRI): 0.468 (0.161-0.752); integrated discriminatory index (IDI): 0.092 (0.035-0.171); likelihood ratio test: P < 0.001] or MAGGIC [NRI: 0.298 (0.106-0.615); IDI: 0.084 (0.033-0.151); likelihood ratio: P < 0.001] scores alone. CONCLUSION: In PH-LHD, pulmonary hemodynamics can provide incremental prognostic value for risk prediction. CLINICAL TRIAL REGISTRATION: NCT02164526 at https://clinicaltrials.gov .

The value of ventricular gradient for predicting pulmonary hypertension and mortality in hemodialysis patients.

Pulmonary hypertension (PHT) is associated with increased mortality in hemodialysis (HD) patients. The ventricular gradient optimized for right ventricular pressure overload (VG-RVPO) is sensitive to early changes in right ventricular overload. The study aimed to assess the ability of the VG-RVPO to detect PHT and predict all-cause and cardiac mortality in HD patients. 265 selected HD patients were enrolled. Clinical, biochemical, electrocardiographic, and echocardiographic parameters were evaluated. Patients were divided into normal and abnormal VG-RVPO groups, and were followed-up for 3 years. Abnormal VG-RVPO patients were more likely to be at high or intermediate risk for PHT, were older, had longer HD vintage, higher prevalence of myocardial infarction, higher parathormone levels, shorter pulmonary flow acceleration time, lower left ventricular ejection fraction, higher values of left atrial volume index, left ventricular mass index, and peak tricuspid regurgitant velocity. Both all-cause and CV mortality were higher in abnormal VG-RVPO group. In multivariate Cox analysis, VG-RVPO remained an independent and strong predictor of all-cause and CV mortality. In HD patients, abnormal VG-RVPO not only predicts PHT, but also all-cause and CV mortality.

Interventricular systolic asynchrony predicts prognosis in patients with systemic sclerosis-associated pulmonary arterial hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a serious complication of SSc with high mortality. Interventricular systolic asynchrony (IVSA) is observed in PAH patients, but the effect of IVSA and its association with long-term mortality and clinical events in SSc-associated PAH are unclear. This study aimed to investigate the impact of IVSA on the prognosis of SSc-associated PAH. METHODS: Between March 2010 and July 2018, a total of 60 consecutive patients with SSc-associated PAH were enrolled. The end point was a composite of all-cause mortality and clinical worsening. Asynchrony was assessed by colour-coded tissue Doppler imaging (TDI) echocardiography. The myocardial sustained systole curves (Sm) of the basal portion of the right ventricular (RV) free wall and left ventricular (LV) lateral wall were obtained. IVSA was defined as the time difference from the onset of the QRS complex to the end of Sm between LV and RV. RESULTS: Patients with greater IVSA time differences presented with advanced pulmonary vascular resistance (PVR). The IVSA time difference was an independent predictive factor (Hazard Ratio (HR) = 1.018, 95% CI: 1.005, 1.031, P =0.005) for the composite end point and was significantly associated with PVR (r = 0.399, R2=0.092, P =0.002). Kaplan-Meier survival curves showed that patients with greater IVSA had worse prognoses (log-rank P =0.001). CONCLUSION: In conclusion, IVSA analysed by colour-coded TDI echocardiography provided added value as a noninvasive, easy-to-use approach for assessing the prognosis of patients with SSc-associated PAH. A significant IVSA time difference identifies the subgroup of patients at high risk of a poor prognosis.

Correlação entre medidas ecocardiográficas e hemodinâmicas na avaliação do átrio direito e ventrículo direito em pacientes com hipertensão pulmonar / Correlation between echocardiographic and hemodynamic measurements in right atrium and right ventricle assessments of patients with pulmonary hypertension

Introdução: Hipertensão Pulmonar (HP), uma condição clínica grave, pode levar à disfunção sistólica do ventrículo direto (DSVD), com implicações prognósticas. Pacientes com suspeita de HP devem ser submetidos ao ecocardiograma transtorácico (ECOTT) para diagnóstico e avaliação, colocando-o como o principal exame de triagem e acompanhamento. Objetivo: Verificar a associação e a concordância das medidas referentes à pressão média no átrio direito (AD) e à disfunção sistólica do ventrículo direto (DSVD) ao (ECOTT) e ao cateterismo de câmaras direitas (CCD) em pacientes com (HP). Métodos: Foram incluídos indivíduos com diagnóstico de (HP). Todos os pacientes foram submetidos ao ECOTT e CCD. Avaliou-se pelo ECOTT: área do átrio direito (AAD), pressão média do átrio direito (AD) através por meio do diâmetro e da colapsabilidade da veia cava inferior (PMADECOTT ), strain AD (SAD), TAPSE (excursão sistólica do plano anular tricúspide), MAF (mudança da área fracional), SPLVD (strain da parede livre do VD) e onda s´ tricuspídea. Pelo CCD avaliaram-se pressão média do (PMADCCD ) e índice cardíaco (IC). Resultados: Dos 16 pacientes, 13 eram do sexo feminino. A idade média foi de 44,4 anos (±14,9). Constataram-se associação entre pressão média do átrio direito PMADCCD com área do átrio direito, PMADECOTT pressão média do átrio direito e SAD strain do átrio direito (r=0,845, r=0,621 e r=-0,523, respectivamente; p< 0,05). Verificou-se associação entre as categorias de risco de mortalidade, mensuradas pelas medidas AAD da área do átrio direito e pressão média do átrio direito PMADCCD (X2=10,42; p=0,003), com concordância moderada (k=0,44; p=0,012). DSVD A disfunção sistólica do ventrículo direto estava presente em dez pacientes. Houve associação entre disfunção sistólica do ventrículo direto DSVD (presente ou ausente) e índice cardíaco IC (r=0,522; p=0,04), com concordância moderada (k=0,43; p=0,037). Conclusão: As medidas do ecocardiograma transtorácico (ECOTT) e cateterismo de câmara direita (CCD) demostraram associação na avaliação da pressão média do átrio direito com melhor associação entre área do átrio direito AAD e pressão média do átrio direito (PMADCCD) . Houve associação com concordância moderada quanto à disfunção sistólica do ventrículo direto (DSVD) entre métodos. (AU)

Introduction: Pulmonary hypertension (PH), a serious clinical condition, can lead to right ventricular systolic dysfunction (RVSD) with prognostic implications. Patients with suspected PH should undergo transthoracic echocardiography (TTE) for diagnosis and evaluation as the main screening and follow-up exam. Objective: To verify the associations of and agreement between measurements of mean pressure in the right atrium (RA) and RVSD with TTE Method: Individuals diagnosed with PH were included. All patients underwent TTE and RCC. The following were evaluated by TTE: right atrial area (RAA), mean right atrial pressure through the diameter and collapsibility of the inferior vena cava (RMAPTTE), RA strain (RAS), tricuspid annular plane systolic excursion, fractional area change, RV free wall strain, and tricuspid s' wave. Mean RA pressure (RMAPRCC) and cardiac index (CI) were evaluated through the RCC. Results: Of the 16 patients, 13 were female. The mean patient age was 44.4 (±14.9) years. An association was found between RMAPRCC and AAD, RMAPTTE, and RAS (r=0.845, r=0.621, and r=-0.523, respectively; p<0.05). There was an association between the mortality risk categories measured by the RAA and RMAPRCC measures (X2=10.42; p=0.003), with moderate agreement (k=0.44; p=0.012). RVSDJ was present in 10 patients. There was an association between RVSD (present or absent) and CI (r=0.522; p=0.04) with moderate agreement (k=0.43; p=0.037). Conclusion: The TTE and RCC measurements showed an association in the assessment of mean right atrial pressure, especially between RAA and RMAPRCC. An association with RVSD and moderate agreement between methods were also noted. (AU)

Outcomes and prognostic factors of decompensated pulmonary hypertension in the intensive care unit.

BACKGROUND: Patients with acute decompensation of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) admitted to intensive care unit (ICU) have high in-hospital mortality. We hypothesized that pulmonary hypertension (PH) severity, measured by a simplified version of European Society of Cardiology/European Respiratory Society (ESC/ERS) risk assessment, and the severity of organ dysfunction upon ICU admission, measured by sequential organ failure assessment score (SOFA) were associated with in-hospital mortality in decompensated patients with PAH and CTEPH. We also described clinical and laboratory variables during ICU stay. METHODS: Observational study including adults with decompensated PAH or CTEPH with unplanned ICU admission between 2014 and 2019. Multivariate logistic regression models were used to evaluate the association of ESC/ERS risk assessment and SOFA score with in-hospital mortality. ESC/ERS risk assessment and SOFA score were included in a decision tree to predict in-hospital mortality. RESULTS: 73 patients were included. In-hospital mortality was 41.1%. ESC/ERS high-risk group (adjusted odds ratio = 95.52) and SOFA score (adjusted odds ratio = 1.80) were associated with in-hospital mortality. The decision tree identified four groups with in-hospital mortality between 8.1% and 100%. Nonsurvivors had a lower central venous oxygen saturation, higher arterial lactate and higher brain natriuretic peptide in the end of first week in the ICU. CONCLUSIONS: High-risk on a simplified version of ERS/ESC risk assessment and SOFA score upon ICU admission are associate with in-hospital mortality. A decision tree based on ESC/ERS risk assessment and SOFA score identifies four groups with in-hospital mortality between 8.1% and 100%.

Characteristics of patients meeting the new definition of pre-capillary pulmonary hypertension (Nice 2018) in a single Japanese pulmonary hypertension center.

BACKGROUND: The 6th World Symposium on Pulmonary Hypertension (Nice 2018) proposed a new definition of pre-capillary pulmonary hypertension (PH) as a condition with mean pulmonary artery pressure (mPAP) > 20 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU). The characteristics and prognosis of patients with pre-capillary PH, according to this new definition, is unclear. Therefore, we determined the characteristics and survival of patients with borderline pre-capillary PH. METHODS: We retrospectively enrolled 683 patients who underwent their first right heart catheterization at Chiba University, Japan. Among them, 489 patients met the pre-capillary PH requirement with mPAP ≥ 25 mmHg (conventional pre-capillary PH group), while 22 patients met the borderline pre-capillary PH criteria (borderline pre-capillary PH group). Additionally, 16 patients with a mean PAP of 20-25 and PVR of 2-3 WU were also examined. RESULTS: The borderline pre-capillary PH group comprised 4.3% of the total patients with pre-capillary PH, and the majority was in Group 3 (40.9%) or 4 (45.5%). The survival of the borderline pre-capillary PH group tended to be better than that of the conventional pre-capillary PH group. The prognosis of Group3 PH was the worst among the patients with borderline precapillary PH. There was no significant difference in survival between the borderline pre-capillary PH group with PVR ≥ 3 WU and that with PVR of 2-3 2WU, although none of the patients in the latter group died due to right heart failure. CONCLUSIONS: This is the first study conducted in a PH center in an Asian country to reveal the characteristics of patients with pre-capillary PH, according to the Nice 2018 definition. They comprised 4.3% of the total population with pre-capillary PH, and the majority of the pre-capillary PH cases were in either Group3 or 4. The prognosis may be affected by the patients' underlying diseases. Further prospective studies are needed to determine whether the new definition, including the PVR cut-off, is beneficial in clinical practice.

Intensive care unit admission for patients with pulmonary hypertension presenting to U.S. Emergency Departments.

INTRODUCTION: Pulmonary hypertension (PH) is an important contributor to morbidity and mortality in patients seeking emergency care, resulting in high acuity presentations and resource utilization. The objective was to characterize the rate of intensive care unit (ICU) admission for PH among adult patients presenting to the emergency department (ED) along with other important clinical outcomes. METHODS: We analyzed data from the State Emergency Department Databases (SEDD) and State Inpatient Databases (SID) from two geographically separated U.S. states (New York and Nebraska). The primary outcome measure was admission to an ICU. Other measures of interest included the hospital admission rate, hospital length of stay (LOS), inpatient mortality, and rate of critical care procedures performed. RESULTS: From 2010 to 2014, in a sample of 34 million ED visits, patients with a diagnosis of PH accounted for 0.71% of all ED visits. Of the PH visits, 20.2% were admitted to the ICU, compared to 2.6% of all other visits (P < 0.001), with an aOR of 1.74 (95% CI 1. 72-1.76). The vast majority (94.6%) of PH patients were admitted to the hospital, compared to 20.5% for all other ED visits (P < 0.001). Hospital LOS and hospital-based mortality were higher in the PH group than for other ED patients. With the exception of invasive mechanical ventilation, a significantly higher percentage of patients with PH admitted to the ICU than other patients underwent all critical care procedures evaluated. CONCLUSIONS: In this study, patients with PH who sought emergency care in U.S. EDs from 2010 to 2014 were significantly more likely to require ICU admission than all other patients. They were also significantly more likely to be admitted to the hospital than all other patients, had longer hospital LOS, increased risk of inpatient mortality, and underwent more critical care procedures. These findings indicate the high acuity of PH patients seeking emergency care and demonstrate the need for additional research into this population.

Pulmonary Artery Hypertension as A Risk Factor for Long-Term Survival after Heart Transplantation.

BACKGROUND: Heart failure is the most frequent cause of pulmonary artery hypertension (PAH) and its severity may predict the development of heart failure (HF) and is known to be a prognostic factor of poor outcome after heart transplant (HTx). The aim of this study was to investigate the impact of preoperative PAH related to left-sided HF on long-term survival after HTx and to identify the hemodynamic parameters of PAH that predict survival after HTx. METHODS: A prospective observational trial was performed, and it included 44 patients subjected to heart transplantation. Patients were divided into two groups: The first one with the preoperative diagnosis of PAH and the second one without the PAH diagnosed prior to the HTx. The two groups were compared for baseline characteristics, operative characteristics, survival, and hemodynamic parameters obtained by right heart catheterization. Survival was analyzed using Kaplan Meyer analysis, and Cox regression analysis was performed to determine independent predictors of survival. RESULTS: The median follow-up time was 637.4 days (1-2028 days). The median survival within the group of patients with preoperative PAH was 1144 days (95% CI 662.884-1625.116) and 1918.920 days (95% CI 1594.577-2243.263) within the group of patients without PAH (P = .023), HR 0.279 (95% [CI]: 0.086-0.910; P = .034. The 30-day mortality in patients within PAH group was significantly higher, six versus two patients in the non PAH group (χ2 = 5.103, P < .05), while the long-term outcome after this period did not differ between the groups. Patients with preoperative PAH had significantly higher values of MPAP, PCWP, TPG and PVRI, while CO and CI did not differ between the two groups. Mean PVRI was 359.1 ± 97.3 dyn·s·cm-5 in the group with preoperative PAH and 232.2 ± 22.75 dyn·s·cm-5 in the group without PAH, P < .001. TPG values were 11.95 ± 5.08 mmHg in the PAH group while patients without PAH had mean values of 5.16 ± 1.97 mmHg, P < .001. Cox regression analysis was done for the aforementioned parameters. Hazard ratio for worse survival after HTx for elevated values of PVRI was 1.006 (95% [CI]: 1.001-1.012; P = .018) TPG had a hazard ratio of 1.172 (95% [CI]: 1.032-1.233; P = .015). CONCLUSION: Pulmonary artery hypertension is an independent risk factor for higher 30-day mortality after HTx, while it does not affect the long-term outcome. Hemodynamic parameters obtained by right heart catheterization in heart transplant candidates could predict postoperative outcome. PVRI and TPG have been identified as independent predictors of higher 30-day postoperative mortality.

Mortality from Pulmonary Hypertension in the Pediatric Cardiac ICU.

Rationale: Patients with pulmonary hypertension (PH) admitted to pediatric cardiac ICUs are at high risk of mortality. Objectives: To identify factors associated with mortality in cardiac critical care admissions with PH. Methods: We evaluated medical admissions with PH to Pediatric Cardiac Critical Care Consortium institutions over 5 years. PH was standardly defined in the clinical registry by diagnosis and/or receipt of intensive care-level pulmonary vasodilator therapy. Multivariable logistic regression identified independent associations with mortality. Measurements and Main Results: We analyzed 2,602 admissions; mortality was 10% versus 3.9% for all other medical admissions. Covariates most strongly associated with mortality included invasive ventilation (adjusted odds ratio, 44.8; 95% confidence interval, 6.2-323), noninvasive ventilation (19.7; 2.8-140), cardiopulmonary resuscitation (8.9; 5.6-14.1), and vasoactive infusions (4.8; 2.6-8.8). Patients receiving both invasive ventilation and vasoactive infusions on admission Days 1 and 2 had an observed mortality rate of 29.2% and 28.6%, respectively, compared with <5% for those not receiving either. Vasoactive infusions emerged as the dominant early risk factor for mortality, increasing the absolute risk of mortality on average by 6.4% when present on admission Day 2. Conclusions: Patients with PH admitted to pediatric cardiac critical care units have high mortality rates. Those receiving invasive ventilation and vasoactive infusions on Day 1 or Day 2 had an observed mortality rate that was more than fivefold greater than that of those who did not. These data highlight the illness severity of patients with PH in this setting and could help inform conversations with families regarding the prognosis.

COVID-19 in Adults With Congenital Heart Disease.

BACKGROUND: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS: From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS: COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.

Protocol: Prospective observational study investigating the prevalence and clinical outcome of portopulmonary hypertension in Japanese patients with chronic liver disease.

BACKGROUND: Portopulmonary hypertension (PoPH) is a subtype of the pulmonary arterial hypertension (PAH) associated with portal hypertension. There is a dissociation between the proportion of PoPH in PAH and that of PoPH in patients with liver cirrhosis, suggesting PoPH underdiagnosis and an incomplete understanding of this entity in the clinical setting. Specifically, real-world data in Japan is largely unknown as compared with in Europe and the United States. The present study aims to elucidate the prevalence and etiology of PoPH in Japanese patients with chronic liver disease. METHODS AND DESIGN: In this prospective, single-center, observational investigation of PoPH patients with chronic liver disease, a targeted 2,500 Japanese adult patients regularly visiting Shinshu University Hospital in Matsumoto, Japan, for chronic liver disease will complete a standardized questionnaire on the presence of PoPH symptoms. If the respondent has signs of possible PoPH, ultrasound echocardiography (UCG) will be performed as a primary screening. In the case that UCG findings indicate pulmonary hypertension, the patient will be referred to a cardiologist for further evaluation, whereby a definitive diagnosis PoPH can be made. PoPH prevalence and etiology will be investigated at the time of diagnosis. Afterwards, patients with PoPH will be followed for five years for determination of survival rate. DISCUSSION: This study will reveal the prevalence, etiology, and 5-year survival rate of PoPH in Japanese patients with chronic liver disease. TRIAL REGISTRATION: This study is being performed at Shinshu University following registration as UMIN 000042287 on October 29, 2020.

Risk prediction in medically treated chronic thromboembolic pulmonary hypertension.

BACKGROUND: At present, there is no generally accepted comprehensive prognostic risk prediction model for medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients. METHODS: Consecutive medically treated CTEPH patients were enrolled in a national multicenter prospective registry study from August 2009 to July 2018. A multivariable Cox proportional hazards model was utilized to derive the prognostic model, and a simplified risk score was created thereafter. Model performance was evaluated in terms of discrimination and calibration, and compared to the Swedish/COMPERA risk stratification method. Internal and external validation were conducted to validate the model performance. RESULTS: A total of 432 patients were enrolled. During a median follow-up time of 38.73 months (IQR: 20.79, 66.10), 94 patients (21.8%) died. The 1-, 3-, and 5-year survival estimates were 95.5%, 83.7%, and 70.9%, respectively. The final model included the following variables: the Swedish/COMPERA risk stratum (low-, intermediate- or high-risk stratum), pulmonary vascular resistance (PVR, ≤ or > 1600 dyn·s/cm5), total bilirubin (TBIL, ≤ or > 38 µmol/L) and chronic kidney disease (CKD, no or yes). Compared with the Swedish/COMPERA risk stratification method alone, both the derived model [C-index: 0.715; net reclassification improvement (NRI): 0.300; integrated discriminatory index (IDI): 0.095] and the risk score (C-index: 0.713; NRI: 0.300; IDI: 0.093) showed improved discriminatory power. The performance was validated in a validation cohort of 84 patients (C-index = 0.707 for the model and 0.721 for the risk score). CONCLUSIONS: A novel risk stratification strategy can serve as a useful tool for determining prognosis and guide management for medically treated CTEPH patients. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01417338).

Mildly Elevated Pulmonary Arterial Pressure Is Associated With a High Risk of Progression to Pulmonary Hypertension and Increased Mortality: A Systematic Review and Meta-Analysis.

Background Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (PAP) ≥25 mm Hg measured by right heart catheterization. However, the upper limit of a normal mean PAP is 20 mm Hg. There is a gap between the upper limit of normal and the threshold for diagnosing PH. Therefore, we aimed to investigate whether individuals with a mildly elevated PAP, defined as 20 mm Hg < mean PAP <25 mm Hg, are at an increased risk of progression to PH or mortality than those with a normal PAP. Methods and Results We reviewed studies evaluating the risk of progression to PH and/or mortality in individuals with a mildly elevated PAP versus those with a normal PAP. The mean PAP value of each participant was confirmed by right heart catheterization. We reviewed 1213 studies and 8 fulfilled our inclusion criteria. Our results indicated that individuals with a mildly elevated PAP were 1.81 to 2.45 times more likely to progress to PH than individuals with a normal PAP. There was a statistically significant difference in mortality between the mildly elevated PAP and normal PAP groups (hazard ratio, 2.48; 95% CI, 1.69-3.64). We also pooled survival probabilities in each arm to obtain a summary survival curve for each group, and the pooled survival rates in the mildly elevated PAP group were numerically lower than those in the normal PAP group. Conclusions Our study revealed that individuals with a mildly elevated PAP were at an increased risk of progression to PH and mortality than those with a normal PAP.

The clinical characteristics, treatment, and survival of portopulmonary hypertension in Japan.

BACKGROUND: Portopulmonary hypertension (PoPH) refers to the simultaneous presentation of pulmonary arterial and portal hypertension. However, few reports have included the characteristics and treatments for patients with PoPH of Asian population; thus, we investigated the clinical characteristics, treatment, and survival of these patients in a Japanese cohort. METHODS: Pulmonary arterial hypertension (PAH) has been included in the National Research Project on Intractable Disease in Japan; therefore, we extracted data of patients with PoPH from the forms of newly registered cases of the project from 2012 to 2013 (for 2 years), and updated cases of the project in 2013 (Study 1, n = 36 newly registered forms, n = 46 updated forms). Additionally, for Study 2, we performed a retrospective, observational cohort study at Chiba University Hospital (n = 11). We compared the characteristics between patients with PoPH and those with idiopathic/heritable PAH (I/H-PAH). RESULTS: Both studies showed higher cardiac outputs (COs) and cardiac indexes (CIs), lower pulmonary vascular resistance (PVR), and less treated with combination therapy in patients with PoPH than those with I/H-PAH. In Study 2, the overall and disease-specific survival between PoPH and I/H-PAH were similar. Conversely, many patients (45%) had to change their PAH-specific medicine because of adverse effects. CONCLUSION: As seen in western countries, Japanese patients with PoPH showed higher COs and CIs, better exercise tolerance, and lower PVRs than patients with I/H-PAH. Further studies are needed to improve PoPH treatments.