Comparison of Contemporary Risk Scores in All Groups of Pulmonary Hypertension: A Pulmonary Vascular Research Institute GoDeep Meta-Registry Analysis.

BACKGROUND: Pulmonary hypertension (PH) is a heterogeneous disease with a poor prognosis. Accurate risk stratification is essential for guiding treatment decisions in pulmonary arterial hypertension (PAH). Although various risk models have been developed for PAH, their comparative prognostic potential requires further exploration. Additionally, the applicability of risk scores in PH groups beyond group 1 remains to be investigated. RESEARCH QUESTION: Are risk scores originally developed for PAH predictive in PH groups 1 through 4? STUDY DESIGN AND METHODS: We conducted a comprehensive analysis of outcomes among patients with incident PH enrolled in the multicenter worldwide Pulmonary Vascular Research Institute GoDeep meta-registry. Analyses were performed across PH groups 1 through 4 and further subgroups to evaluate the predictive value of PAH risk scores, including Registry to Evaluate Early and Long-Term PAH Disease Mangement (REVEAL) Lite 2, REVEAL 2.0, ESC/ERS 2022, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 3-strata, and COMPERA 4-strata. RESULTS: Eight thousand five hundred sixty-five patients were included in the study, of whom 3,537 patients were assigned to group 1 PH, whereas 1,807 patients, 1,635 patients, and 1,586 patients were assigned to group 2 PH, group 3 PH, and group 4 PH, respectively. Pulmonary hemodynamics were impaired with median mean pulmonary arterial pressure of 42 mm Hg (interquartile range, 33-52 mm Hg) and pulmonary vascular resistance of 7 Wood units (WU) (interquartile range, 4-11 WU). All risk scores were prognostic in the entire PH population and in each of the PH groups 1 through 4. The REVEAL scores, when used as continuous prediction models, demonstrated the highest statistical prognostic power and granularity; the COMPERA 4-strata risk score provided subdifferentiation of the intermediate-risk group. Similar results were obtained when separately analyzing various subgroups (PH subgroups 1.1, 1.4.1, and 1.4.4; PH subgroups 3.1 and 3.2; group 2 with isolated postcapillary PH vs combined precapillary and postcapillary PH; patients of all groups with concomitant cardiac comorbidities; and severe [> 5 WU] vs nonsevere PH). INTERPRETATION: This comprehensive study with real-world data from 15 PH centers showed that PAH-designed risk scores possess predictive power in a large PH cohort, whether considered as common to the group or calculated separately for each PH group (1-4) and various subgroups. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT05329714; URL: www. CLINICALTRIALS: gov.

Using PAH-SYMPACT to assess quality of life in patients with pulmonary hypertension associated with chronic lung disease.

Chronic lung disease (CLD) is the second leading cause of pulmonary hypertension (PH) and is associated with significant morbidity and mortality. Although PH associated with CLD (PH-CLD) leads to impaired health-related quality of life (HRQOL), there are no validated tools to assess HRQOL in PH-CLD. The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT) is an HRQOL instrument aimed at assessing the symptoms and impact of PH on overall function and well-being. We performed a single-center prospective cohort study using PAH-SYMPACT scores to compare symptoms, exercise capacity and HRQOL in patients with PAH and PH-CLD. One hundred and twenty-five patients (99 patients with idiopathic/heritable PAH and 26 with PH-CLD) completed the PAH-SYMPACT questionnaire which consists of 22 questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive/emotional (CE) impact. Higher scores indicate worse HRQOL. We compared patients with PAH and PH-CLD using a Wilcoxon rank sum or chi-squared test as appropriate. Multivariate linear regression analysis was used to assess the relationship between PH classification and SYMPACT scores. Compared to PAH, patients with PH-CLD were older, more likely to use oxygen and had worse functional class and exercise capacity. While there was no significant difference between the two groups in CP, CV, or CE domain scores, patients with PH-CLD had significantly worse PI scores by univariate (1.79 vs. 1.13, p < 0.001) and multivariate analysis (1.61 vs. 1.17, p = 0.02) and overall worse SYMPACT scores (1.19 vs. 0.91, p = 0.03). In conclusion, patients with PH-CLD have worse HRQOL as assessed by the PAH-SYMPACT questionnaire versus patients with PAH. Although PAH-SYMPACT has not been validated in PH-CLD, the results of this study can guide clinicians in understanding the symptoms and impact of PH-CLD relative to PAH.

Complications of Right Heart Catheterization in Patients ≥70 Years of Age With Suspected Pulmonary Hypertension: Experience From a Tertiary Care Center.

Right heart catheterization (RHC) represents the gold standard diagnostic approach for pulmonary hypertension (PH). Historically, the complication rates of RHC are known to be low. The study aimed to evaluate the indications for performing RHC and the occurrence of adverse events related to the procedure in patients > over 70 years of age in a Mexican Tertiary Care Center. We conducted a retrospective single-center registry from July 2017 to July 2022. A total of 517 patients with suspected PH underwent RHC. The cohort included patients <70 (n = 427) and ≥70 years of age (n = 90). Adverse events were classified as major (eg, death, pneumothorax, and carotid artery puncture) and minor (eg, atrial arrhythmia, superior vena cava dissection, incidental arterial puncture, and local hematoma). Appropriate hemodynamic parameters were recorded. No report of major adverse events in the entire cohort. In the <70 years age group, 9 minor events, and 3 minor events were in the ≥70-year-old patients (P < 0.0001). There was a significant difference in the measurement of mean pulmonary artery pressure (mPAP) between the <70 years old vs ≥70 years old (P < 0.001); there was a significant difference in right atrial pressures: 4.71 ± 3.14 mmHg in the <70-year-old vs 4.07 ± 1.94 mmHg for the ≥ 70-year-old group (P = 0.014). Our findings suggest that RHC can be safely performed in patients aged ≥70 years using different vascular access routes without significant major complications.

Quantitative CT measures of pulmonary vascular volume distribution in pulmonary hypertension associated with COPD: Association with clinical characteristics and outcomes.

To determine whether quantitative computed tomography (qCT)-derived metrics of pulmonary vascular volume distribution could distinguish chronic obstructive pulmonary disease (COPD) subjects with associated pulmonary hypertension (PH) from those without and to characterize associations of these measurements with clinical and physiological characteristics and outcomes. We collected retrospective CT, pulmonary hemodynamic, clinical, and outcomes data from subjects with COPD and right-heart catheterization-confirmed PH (PH-COPD) and control subjects with COPD but without PH. We measured the volumes of pulmonary vessels < 5 and >10 mm2 in cross-sectional area as a percentage of total pulmonary vascular volume (qCT-derived volume of pulmonary vessels < 5 mm2 in cross-sectional area as a volume fraction of total pulmonary blood volume [BV5%] and qCT-derived volume of pulmonary vessels > 10 mm2 in cross-sectional area [BV10] as a volume fraction of total pulmonary blood volume [BV10%], respectively) using Functional Respiratory Imaging (FRI), an automated qCT platform, and compared them between PH and control arms and between subjects with mild-moderate PH and those with severe disease. Correlations of hemodynamics with pulmonary function and associations with survival were tested. Forty-five PH-COPD and 42 control subjects were studied. BV5% was lower in PH subjects (32.2% vs. 37.7%, p = 0.003), and BV10% was higher (50.2% vs. 43.5, p = 0.001). Subjects with severe PH did not differ from those with mild-moderate PH in qCT. Pulmonary vascular volumes were not associated with pulmonary function. BV10 was associated with mean pulmonary artery pressure (r = 0.3, p = 0.05). Associations with survival were observed for BV5% (hazard ratio 0.63, p = 0.02) and BV10% (hazard ratio 1.43, p = 0.03) in the PH-COPD arm, but not for controls. qCT-derived measures of pulmonary vascular volume may have diagnostic and prognostic significance in PH-COPD and should be investigated further as screening and risk stratification tools.

Portopulmonary Hypertension in Nontransplanted Patients: Results of the Largest US Single-Institution Registry.

OBJECTIVE: To explore clinical characteristics, risk profiles, and outcomes of patients with portopulmonary hypertension (PoPH) who have contraindications to liver transplant (LT). METHODS: From the largest US single-institution registry of patients with PoPH, we analyzed 160 patients who did not receive LT between 1988 to 2019. Pulmonary arterial hypertension (PAH)-pertinent characteristics, hemodynamic features, treatments, and risk stratification were compared at baseline, first follow-up visit, and censor/death time. RESULTS: Median survival for the entire cohort was 27.5 months from the diagnosis of PoPH. Overall survival was 89%, 77%, 51%, and 38% at 6 months, 1 year, 3 years, and 5 years, respectively. Survival was significantly affected by the severity of liver disease (P<.001). Most patients received PAH-specific therapies (136 [85%]), predominantly monotherapy (123 [77%)]. With treatment, significant improvements were noted in World Health Organization functional class (P=.04), 6-minute walk distance (P<.001), right ventricular function (P<.001), pulmonary vascular resistance (P<.001), and Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) Lite 2 score (P=.02) univariately. Per European Society of Cardiology risk stratification, no patient met full criteria for low risk at baseline or at follow-up. In a multivariate Cox risk model, 6-minute walk distance, right atrial pressure, pulmonary capillary wedge pressure, bilirubin level, and Model for End-Stage Liver Disease-sodium score of 15 or higher were associated with increased risk of death. CONCLUSION: Patients with PoPH who did not undergo LT had a poor prognosis. This persisted despite use of PAH-specific therapies and significant improvements in hemodynamics, echocardiography parameters of right ventricle function, 6-minute walk distance, and World Health Organization functional class.

Bezold-Jarisch reflex mediated syncope in pulmonary arterial hypertension: An illustrative case series.

We present a novel description of Bezold-Jarisch Reflex (BJR) during cardiopulmonary exercise testing (CPET) in three young female patients with Group 1 pulmonary arterial hypertension (PAH). These three cases presented within 26 months, representing only 0.8% of 11,387 tests on patients with PAH undergoing CPET during this time frame.

The feasibility and value of assessing patient-reported outcomes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that negatively impacts health-related quality of life (HRQOL). The PAH-symptoms and impact (PAH-SYMPACT) questionnaire is a validated disease-specific patient-reported outcome (PRO) instrument that assesses a patient's symptoms and the impact of PAH and its treatment on well-being. We performed a single-center prospective cohort study of patients with PAH to determine the feasibility of assessing PROs in clinical practice and to determine the association between PAH-SYMPACT domains and clinical characteristics and outcomes. One hundred and ten patients completed the 1-day version of the PAH-SYMPACT questionnaire which consists of 22 Likert-scale questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive and emotional (CE) impact. Higher scores indicate worse HRQOL. Patients were predominantly female (n = 86, 78%) with a mean age of 57.8 ± 16.2 years. While several patient characteristics were associated with CP and PI domains, few were associated with CV and CE domains. PI and CE impact scores were associated with recent hospitalizations and mortality and CE impact score was independently associated with an increased risk of death after adjustment for disease severity (hazard ratio: 3.29, 95% confidence interval: 1.56-6.91, p = 0.002). In conclusion, the assessment of PROs in clinical practice using the PAH-SYMPACT questionnaire is both feasible and valuable. PAH-SYMPACT scores have independent prognostic value and are not adequately reflected by traditional measures of disease severity. These findings underscore the importance of assessing HRQOL in clinical practice.

Pulmonary Vascular Research Institute GoDeep: A meta-registry merging deep phenotyping datafrom international PH reference centers.

The Pulmonary Vascular Research Institute GoDeep meta-registry is a collaboration of pulmonary hypertension (PH) reference centers across the globe. Merging worldwide PH data in a central meta-registry to allow advanced analysis of the heterogeneity of PH and its groups/subgroups on a worldwide geographical, ethnical, and etiological landscape (ClinTrial. gov NCT05329714). Retrospective and prospective PH patient data (diagnosis based on catheterization; individuals with exclusion of PH are included as a comparator group) are mapped to a common clinical parameter set of more than 350 items, anonymized and electronically exported to a central server. Use and access is decided by the GoDeep steering board, where each center has one vote. As of April 2022, GoDeep comprised 15,742 individuals with 1.9 million data points from eight PH centers. Geographic distribution comprises 3990 enrollees (25%) from America and 11,752 (75%) from Europe. Eighty-nine perecent were diagnosed with PH and 11% were classified as not PH and provided a comparator group. The retrospective observation period is an average of 3.5 years (standard error of the mean 0.04), with 1159 PH patients followed for over 10 years. Pulmonary arterial hypertension represents the largest PH group (42.6%), followed by Group 2 (21.7%), Group 3 (17.3%), Group 4 (15.2%), and Group 5 (3.3%). The age distribution spans several decades, with patients 60 years or older comprising 60%. The majority of patients met an intermediate risk profile upon diagnosis. Data entry from a further six centers is ongoing, and negotiations with >10 centers worldwide have commenced. Using electronic interface-based automated retrospective and prospective data transfer, GoDeep aims to provide in-depth epidemiological and etiological understanding of PH and its various groups/subgroups on a global scale, offering insights for improved management.

The impact of pulmonary hypertension on outcomes of transcatheter mitral valve replacement in mitral annular calcification.

OBJECTIVES: To assess the impact of pulmonary hypertension (PH) on outcomes of patients with severe mitral annular calcification (MAC) undergoing transcatheter mitral valve replacement (TMVR). BACKGROUND: PH is associated with poor outcomes after mitral valve surgery. Whether the presence of PH in patients with MAC undergoing (TMVR) is associated with poor outcomes, is unknown. METHODS: Retrospective evaluation of 116 patients from 51 centers in 11 countries who underwent TMVR with valve in mitral annular calcification (ViMAC) using balloon-expandable aortic transcatheter valves (THVs) from September 2012 to March 2017. Pulmonary artery systolic blood pressure (PASP) by echocardiogram was available in 90 patients. The subjects were stratified based on PASP: No PH = PASP ≤35 mmHg (n = 11); mild to moderate PH = PASP 36-49 mmHg (n = 21) and severe PH = PASP ≥50 mmHg (n = 58). Clinical, procedural, and echocardiographic outcomes were assessed. RESULTS: Mean age was 72.7 (±12.8) years, 59 (65.6%) were female, Society of Thoracic Surgeons score was 15.8 + 11.8% and 90.0% where in New York Heart Association (NYHA) class III-IV. There was no significant difference in all-cause mortality at 30 days (no PH = 27.3%, mild-moderate PH = 19.0%, severe PH = 31.6%; p = 0.55) or at 1 year (no PH = 54.5%, mild-moderate PH = 38.1%, severe PH = 56.1%; p = 0.36). No difference in adverse events, NYHA class or amount of residual mitral regurgitation at 1 year were observed between the groups. CONCLUSION: This study suggests that the presence of PH in patients with predominantly mitral stenosis with MAC undergoing TMVR does not impact mortality or adverse events. Further studies are needed to fully understand the effect of PH in this group of patients.

ICU and Hospital Outcomes in Patients with Hepatopulmonary Syndrome Undergoing Liver Transplantation.

PURPOSE: There are limited data regarding hospital and intensive care unit (ICU) outcomes in patients with hepatopulmonary syndrome (HPS) following liver transplantation (LT). METHODS: Data were retrospectively collected from consecutive HPS adult patients who underwent LT and were immediately admitted to the ICU at three transplant centers with shared management protocols, from 2002 to 2018. Demographic, clinical, surgical, laboratory, and outcome data were extracted. RESULTS: We identified 137 patients (74 male, 54%), with a median age at LT of 58 years (IQR: 52-63). One hundred and 31 (95.6%) patients were admitted to the ICU on invasive mechanical ventilation (MV). The median time on invasive MV in the ICU was 12 hours (IQR: 5-28) and 97 patients (74%) were extubated within 24 hours of ICU admission. The median highest positive end expiratory pressure and fraction of inspired oxygen (FiO2) were 7 (IQR: 5-8) and 0.6 (IQR: 0.5-0.7), respectively. 7 patients (5%) developed severe post-transplant hypoxemia. Of all patients, 42 (30.4%) required vasopressors and the median ICU and hospital length of stay (LOS) were 3 (IQR: 1-5) and 10 (IQR: 7-20) days, respectively. The in-hospital mortality rate was 3.6% (5/137). HPS severity was not associated with hospital mortality. CONCLUSION: Most HPS patients have short durations of MV, ICU, and hospital LOS post-LT. HPS severity does not impact hospital mortality.

Outcomes of liver transplantation in patients with hepatopulmonary syndrome in the pre and post-MELD eras: A systematic review.

BACKGROUND: The lack of large hepatopulmonary syndrome cohorts undergoing liver transplantation (LT) has resulted in limited information about post-LT outcomes and expectations. METHODS: The long and short-term outcomes of LT in patients with hepatopulmonary syndrome (HPS) were evaluated before and after the implementation of Model for Endstage Liver Disease (MELD) score in 2002, granting exception points for patients with HPS. PubMed/Medline, Embase, Web of Science and Scopus databases were searched for published and unpublished studies from 01/1990 to 04/2019. Studies that included HPS patients who underwent LT and reported post-LT outcomes and HPS severity were reviewed. After reviewing the full text of 1421 articles, 30 were included in the pre-MELD era (before 2002) and 60 in the post-MELD era. RESULTS: A total of 598 patients (210 children and 388 adults) with HPS who underwent LT were included in this systematic review. In children, 5-year survival probability was similar in the pre and post-MELD groups (85.7% vs. 97.4; p = 0.09). Median post-transplant PaO2 in room air was higher in the post-MELD group (71 [53-87] vs. 97 [80-108] mmHg: p = 0.008). In adults, 5-year survival probability was higher in the post-MELD era (73 vs. 87.3%; p = 0.008). Median post-transplant PaO2 in room air was higher in post-MELD group (75 [63-85] vs. 87 [75-95] mmHg; p = 0.001).. CONCLUSIONS: After MELD exception implementation, survival rates and post-transplant oxygenation improved in adult patients with HPS who underwent liver transplantation, whereas only post-transplant oxygenation improved in children.

Healthcare Utilization and Costs associated with Hereditary Hemorrhagic Telangiectasia Patients in a Large US Claims Database.

OBJECTIVE: To assess the health care costs and utilization in patients with hereditary hemorrhagic telangiectasia (HHT) in the United States. PATIENTS AND METHODS: Retrospective analysis of patients with HHT diagnosed between 2007 and 2017 was performed using deidentified administrative claims data from the OptumLabs Data Warehouse. Adult patients with new (incident) diagnosis of HHT between January 1, 2007, and December 31, 2017, were included. Comparisons were made using the Wilcoxon rank sum test. RESULTS: Three thousand nine hundred seventy-seven patients with a first diagnosis of HHT between 2007 and 2017 were identified, of which 3590 were matched 1:1 to non-HHT patients with similar baseline characteristics and comorbidities. These 3590 patients with HHT were 63.1% female and 83.9% white with a mean age of 51.1 ± 18.5 years, and a mean follow-up period of 3.2 ± 2.2 years (range, 1.0-11.7 years). Compared with the control group, the cumulative 5-year median total health care cost for patients with HHT was 41.4% higher ($21,118 vs $14,929; P < .001) in those with private commercial insurance and 31.7% higher ($35,462 vs $26,925; P < .001) in those with Medicare Advantage coverage. The median annual health care costs were significantly higher in patients with HHT with commercial insurance and Medicare Advantage in the first year after diagnosis ($4,333 vs $1,804; P < .001), and ($7,322 vs $5,245; P < .001), respectively, and remained higher throughout the duration of follow-up. Further analysis showed that outpatient clinic visits, hospital admission, imaging rates, invasive procedures, iron infusions, and blood transfusions were all significantly higher in the HHT group. CONCLUSION: Patients with HHT have significantly higher health care costs compared with a matched control group. A better understanding of the reasons underlying these cost differences will provide opportunities for patients, providers, and other stakeholders to better manage this rare condition.

Impact of Right Ventricular Dysfunction on Short-term and Long-term Mortality in Sepsis: A Meta-analysis of 1,373 Patients.

BACKGROUND: Right ventricular (RV) dysfunction in sepsis and septic shock has been infrequently studied and has uncertain prognostic significance. RESEARCH QUESTION: Does RV function impact mortality in sepsis and septic shock? STUDY DESIGN AND METHODS: We reviewed the published literature from January 1999 to April 2020 for studies evaluating adult patients with sepsis and septic shock. Study definition of RV dysfunction was used to classify patients. The primary outcome was all-cause mortality divided into short-term mortality (ICU stay, hospital stay, or mortality ≤30 days) and long-term mortality (>30 days). Effect estimates from the individual studies were extracted and combined, using the random-effects, generic inverse variance method of DerSimonian and Laird. RESULTS: Ten studies, 1,373 patients, were included; RV dysfunction was noted in 477 (34.7%). RV dysfunction was variably classified as decreased RV systolic motion, high RV/left ventricular ratio and decreased RV ejection fraction. Septic shock, ARDS, and mechanical ventilation were noted in 82.0%, 27.5%, and 78.4% of the population, respectively. Patients with RV dysfunction had lower rates of mechanical ventilation (71.9% vs 81.9%; P < .001), higher rates of acute hemodialysis (38.1% vs 22.4%; P = .04), but comparable rates of septic shock and ARDS. Studies showed moderate (I2 = 58%) and low (I2 = 49%) heterogeneity for short-term and long-term mortality, respectively. RV dysfunction was associated with higher short-term (pooled OR, 2.42; 95%CI, 1.52-3.85; P = .0002) (10 studies) and long-term (pooled OR, 2.26; 95%CI, 1.29-3.95; P = .004) (4 studies) mortality. INTERPRETATION: In this meta-analysis of observational studies, RV dysfunction was associated with higher short-term and long-term mortality in sepsis and septic shock.

Clinical Outcomes After Liver Transplantation in Patients With Portopulmonary Hypertension.

BACKGROUND: Portopulmonary hypertension (POPH) is the presence of pulmonary arterial (PA) hypertension in patients with portal hypertension and is associated with significant morbidity and mortality. In a cohort of POPH patients, we describe the clinical outcomes of POPH patients who underwent liver transplantation (LT). METHODS: Retrospectively collected data from a prospectively assembled cohort of all consecutive POPH adults evaluated in 3 transplant centers from 1996 to 2019. RESULTS: From a cohort of 228 POPH patients, 50 patients underwent LT. Significant hemodynamic improvement after PA-targeted therapy was observed, with 58% receiving only monotherapy pretransplant. After LT, 21 (42%) patients were able to discontinue and remained off PA-targeted therapy. The 1-, 3-, and 5-y unadjusted survival rates after LT were 72%, 63%, and 60%, respectively. An elevated pulmonary vascular resistance (PVR) before LT was associated with worse survival rate (HR, 1.91; 95% CI, 1.07-3.74, P = 0.04). No survival difference was observed in those granted MELD exception or transplants performed before or after the year 2010. CONCLUSIONS: Significant number of POPH patients discontinued PA-targeted therapy after LT. Higher PVR before LT was associated with worse survival, as was monotherapy use. Despite effective PA-targeted therapies, POPH survival outcomes after LT in our cohort were modest and may reflect the need for more aggressive therapy.

Inpatient Palliative Care Use in Patients With Pulmonary Arterial Hypertension: Temporal Trends, Predictors, and Outcomes.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease associated with significant morbidity and mortality. Despite the negative impact of PAH on quality of life and survival, data on use of specialty palliative care services (PCS) is scarce. RESEARCH QUESTION: We sought to evaluate the inpatient use of PCS in patients with PAH. STUDY DESIGN AND METHODS: Using the National (Nationwide) Inpatient Sample, 30,495 admissions with a primary diagnosis of PAH were identified from 2001 through 2017. The primary outcome of interest was temporal trends and predictors of inpatient PCS use in patients with PAH. RESULTS: The inpatient use of PCS was low (2.2%), but increased during the study period from 0.5% in 2001 to 7.6% in 2017, with a significant increase starting in 2009. White race, private insurance, higher socioeconomic status, hospital-specific factors, higher comorbidity burden (Charlson Comorbidity Index), cardiac and noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation were independent predictors of increased PCS use. PCS use was associated with a higher prevalence of do-not-resuscitate status, a longer length of stay, higher hospitalization costs, and increased in-hospital mortality with less frequent discharges to home, likely because these patients were also sicker (higher comorbidity index and illness acuity). INTERPRETATION: The inpatient use of PCS in patients with PAH is low, but has been increasing over recent years. Despite increased PCS use over time, patient- and hospital-specific disparities in PCS use continue. Further studies evaluating these disparities and the role of PCS in the comprehensive care of PAH patients are warranted.

Intravenous Bevacizumab in Hereditary Hemorrhagic Telangiectasia-Related Bleeding and High-Output Cardiac Failure: Significant Inter-Individual Variability in the Need for Maintenance Therapy.

OBJECTIVE: To present our center's experience with a maintenance treatment algorithm for intravenous bevacizumab that allows for personalized therapy decisions. PATIENTS AND METHODS: We reviewed all patients treated with intravenous bevacizumab for hereditary hemorrhagic telangiectasia-related bleeding and/or high-output cardiac failure (HOCF) from January 1, 2013, to July 1, 2019, at the Mayo Clinic, Rochester, Minnesota. Data regarding subsequent bevacizumab dosing were abstracted. RESULTS: A total of 57 patients (n=40, 70.2% females) were identified with a median age of 65 (55 to 74; range, 37 to 89) years. High-cardiac output state was present in 21 patients (36.8%) and 10 (17.5%) were treated with intravenous bevacizumab primarily for HOCF. The median duration of follow-up after completion of the initial intravenous bevacizumab treatment was 25 (12.3 to 40.8; range, 0.1 to 65.4) months. A total of 20 (35.1%) patients with a median follow-up of 13.5 (range, 0 to 48.4) months required no maintenance dosing throughout the duration of follow-up. Among those who required subsequent maintenance doses, only a small fraction (8 patients; 14.0%) required regular maintenance doses every 4 to 8 weeks during follow-up whereas the majority of patients required intermittent "as-needed" doses at varying intervals. CONCLUSION: There is significant inter-individual variability in the need for maintenance intravenous bevacizumab when patients are followed using a predefined bevacizumab maintenance dosing treatment algorithm. The use of "as-needed" maintenance bevacizumab appears to be an effective strategy for management of hereditary hemorrhagic telangiectasia-related bleeding and HOCF.

A Cardiac Computed Tomography-Based Score to Categorize Mitral Annular Calcification Severity and Predict Valve Embolization.

OBJECTIVES: This study aims to establish a computed tomography (CT)-based scoring system for grading mitral annular calcification (MAC) severity and potentially aid in predicting valve embolization during transcatheter mitral valve (MV) replacement using balloon-expandable aortic transcatheter heart valves. BACKGROUND: Transcatheter MV replacement is emerging as an alternative treatment for patients with severe MAC who are not surgical candidates. Although cardiac CT is the imaging modality of choice in the evaluation of candidates for valve-in-MAC (ViMAC), a standardized grading system to quantify MAC severity has not been established. METHODS: We performed a multicenter retrospective review of cardiac CT and clinical outcomes of patients undergoing ViMAC. A CT-based MAC score was created using the following features: average calcium thickness (mm), degrees of annulus circumference involved, calcification at one or both fibrous trigones, and calcification of one or both leaflets. Features were assigned points according to severity (total maximum score = 10) and severity grade was assigned based on total points (mild ≤3, moderate 4 to 6, and severe ≥7 points). The association between MAC score and device migration/embolization was evaluated. RESULTS: Of 117 patients in the TMVR in MAC registry, 87 had baseline cardiac CT of adequate quality. Of these, 15 were treated with transatrial access and were not included. The total cohort included 72 (trans-septal = 37, transapical = 35). Mean patient age was 74 ± 12 years, 66.7% were female, and the mean Society of Thoracic Surgery risk score was 15.4 ± 10.5%. The mean MAC score was 7.7 ± 1.4. Embolization/migration rates were lower in higher scores: Patients with a MAC score of 7 had valve embolization/migration rate of 12.5%, MAC score ≥8 had a rate of 8.7%, and a MAC score of ≥9 had zero (p = 0.023). Patients with a MAC score of ≤6 had 60% embolization/migration rate versus 9.7% in patients with a MAC score ≥7 (p < 0.001). In multivariable analysis, a MAC score ≤6 was in independent predictor of valve embolization/migration (odds ratio [OR]: 5.86 [95% CI: 1.00 to 34.26]; p = 0.049). CONCLUSIONS: This cardiac CT-based score provides a systematic method to grade MAC severity which may assist in predicting valve embolization/migration during trans-septal or transapical ViMAC procedures.

Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery.

Cardiac glycosides (CGs) are used primarily for cardiac failure and have been reported to have other effects, including inhibition of viral replication. Here we set out to study mechanisms by which CGs as inhibitors of the Na-K-ATPase decrease influenza A virus (IAV) replication in the lungs. We found that CGs inhibit influenza virus replication in alveolar epithelial cells by decreasing intracellular potassium, which in turn inhibits protein translation, independently of viral entry, mRNA transcription, and protein degradation. These effects were independent of the Src signaling pathway and intracellular calcium concentration changes. We found that short-term treatment with ouabain prevented IAV replication without cytotoxicity. Rodents express a Na-K-ATPase-α1 resistant to CGs. Thus we utilized Na-K-ATPase-α1-sensitive mice, infected them with high doses of influenza virus, and observed a modest survival benefit when treated with ouabain. In summary, we provide evidence that the inhibition of the Na-K-ATPase by CGs decreases influenza A viral replication by modulating the cell protein translational machinery and results in a modest survival benefit in mice.