Pulmonary artery compliance in different forms of pulmonary hypertension.

OBJECTIVE: Pulmonary artery compliance (PAC), estimated as stroke volume (SV) divided by pulmonary artery pulse pressure (PP), may be a predictor of survival in pulmonary arterial hypertension (PAH). Resistance-compliance (RC) time, the product of PAC and pulmonary vascular resistance, is reported to be a physiological constant. We investigated if differences in PAC and RC time exist between pulmonary hypertension (PH) subgroups and examined whether PAC is an independent predictor of transplant-free survival in PAH. METHODS: This was a retrospective analysis of adult PAH (n=532) and chronic thromboembolic PH (CTEPH, n=84) patients enrolled in the US Pulmonary Hypertension Association Registry from 2015 to 2019. PAC and RC time were compared between PH subgroups (connective tissue disease-PAH (CTD-PAH), idiopathic/heritable-PAH (i/h-PAH), drug/toxin-PAH (d/t-PAH)). Cox proportional hazards models were constructed for transplant-free survival, adjusting for REVEAL 2.0 risk score. RESULTS: There were no differences in estimated PAC between PAH subgroups, nor between PAH and CTEPH. RC time was shorter in CTEPH compared with PAH (median 0.55 (IQR 0.45-0.64) vs 0.62 (0.52-0.73) s, p<0.0001). RC time was shortest in CTD-PAH when compared with i/h-PAH and d/t-PAH ((0.59±0.18) vs (0.65±0.20) vs (0.73±0.25) s, p=0.0001). PAC was associated with transplant-free survival (HR 0.72, 95% CI 0.55 to 0.94, p=0.02) but was not an independent predictor of outcome after adjustment for REVEAL 2.0 score. CONCLUSION: PAC was similar between PH groups and was not an independent predictor of transplant-free survival in PAH. RC time was different between PH subgroups, challenging RC time constancy. TRIAL REGISTRATION NUMBER: NCT04071327.

Delphi consensus recommendation for optimization of pulmonary hypertension therapy focusing on switching from a phosphodiesterase 5 inhibitor to riociguat.

Dual combination therapy with a phosphodiesterase-5 inhibitor (PDE5i) and endothelin receptor antagonist is recommended for most patients with intermediate-risk pulmonary arterial hypertension (PAH). The RESPITE and REPLACE studies suggest that switching from a PDE5i to a soluble guanylate cyclase (sGC) activator may provide clinical improvement in this situation. The optimal approach to escalation or transition of therapy in this or other scenarios is not well defined. We developed an expert consensus statement on the transition to sGC and other treatment escalations and transitions in PAH using a modified Delphi process. The Delphi process used a panel of 20 physicians with expertise in PAH. Panelists answered three questionnaires on the management of treatment escalations and transitions in PAH. The initial questionnaire included open-ended questions. Later questionnaires consolidated the responses into statements that panelists rated on a Likert scale from -5 (strongly disagree) to +5 (strongly agree) to determine consensus. The Delphi process produced several consensus recommendations. Escalation should be considered for patients who are at high risk or not achieving treatment goals, by adding an agent from a new class, switching from oral to parenteral prostacyclins, or increasing the dose. Switching to a new class or within a class should be considered if tolerability or other considerations unrelated to efficacy are affecting adherence. Switching from a PDE5i to an SGC activator may benefit patients with intermediate risk who are not improving on their present therapy. These consensus-based recommendations may be helpful to clinicians and beneficial for patients when evidence-based guidance is unavailable.

Erratum: Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: An analysis of the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211020913.].

Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: an analysis of the Pulmonary Hypertension Association Registry.

Compared to idiopathic pulmonary arterial hypertension (IPAH), patients with portopulmonary hypertension (POPH) have worse survival. Health disparities may contribute to these differences but have not been studied. We sought to compare socioeconomic factors in patients with POPH and IPAH and to determine whether socioeconomic status and/or POPH diagnosis were associated with treatment and health-care utilization. We performed a cross-sectional study of adults enrolled in the Pulmonary Hypertension Association Registry. Patients with IPAH (n = 344) and POPH (n = 57) were compared. Compared with IPAH, patients with POPH were less likely to be college graduates (19.6% vs. 34.9%, p = 0.02) and more likely to be unemployed (54.7% vs. 30.5%, p < 0.001) and have an annual household income below poverty level (45.7% vs. 19.0%, p < 0.001). Patients with POPH had similar functional class, quality of life, 6-min walk distance, and mean pulmonary arterial pressure with a higher cardiac index. Compared with IPAH, patients with POPH were less likely to receive combination therapy (46.4% vs. 62.2%, p = 0.03) and endothelin receptor antagonists (28.6% vs. 55.1%, p < 0.001) at enrollment with similar treatment at follow-up. Patients with POPH had more emergency department visits (1.7 ± 2.1 vs. 0.9 ± 1.2, p = 0.009) and hospitalizations in the six months preceding enrollment (1.5 ± 2.1 vs. 0.8 ± 1.1, p = 0.02). Both POPH diagnosis and lower education level were independently associated with a higher number of emergency department visits. Compared to IPAH, patients with POPH have lower socioeconomic status, are less likely to receive initial combination therapy and endothelin receptor antagonists but have similar treatment at follow-up, and have increased health-care utilization.

Age-related differences in hemodynamics and functional status in pulmonary arterial hypertension: Baseline results from the Pulmonary Hypertension Association Registry.

BACKGROUND: The age of patients with pulmonary arterial hypertension (PAH) has increased, with registries now reporting mean ages of 50 to 65 years old. Limited data exist on age-related differences in hemodynamic and functional assessments in PAH. METHODS: Adults with PAH in the Pulmonary Hypertension Association Registry were divided into 3 groups (18-50, 51-65, and >65 years old). Analysis of variance and chi-square testing were used to assess for baseline differences. Linear regression was used to examine the association of age with continuous hemodynamic and functional variables. RESULTS: A total of 769 patients with mean age of 56 ± 16 years were included. Older patients had more connective tissue disease-associated PAH and less drug-associated PAH. In linear regression models, each year of increased age was associated with shorter 6-minute walk distance (-3.37 meters; 95% CI, -3.97 to -2.76), lower mean pulmonary arterial pressure (-0.21 mm Hg; 95% CI, -0.27 to -0.15), and lower pulmonary vascular resistance (-0.06 Wood units; 95% CI, -0.09 to -0.04). Pulmonary arterial compliance, cardiac index, right ventricular stroke work index, and percent predicted 6-minute walk distance were unrelated to age; resistance-compliance time was negatively related to age (-3 milliseconds per year; 95% CI, -4 to -2). CONCLUSIONS: Relative to their pulmonary vascular resistance, older patients have lower pulmonary artery compliance and worse right ventricular performance. Based on these findings, we suspect that age influences right ventricular loading conditions and the response of the right ventricle to increased afterload.

Residence at moderately high altitude and its relationship with WHO Group 1 pulmonary arterial hypertension symptom severity and clinical characteristics: the Pulmonary Hypertension Association Registry.

BACKGROUND: WHO Group 1 pulmonary arterial hypertension is a progressive and potentially fatal disease. Individuals living at higher altitude are exposed to lower barometric pressure and hypobaric hypoxemia. This may result in pulmonary vasoconstriction and contribute to disease progression. We sought to examine the relationship between living at moderately high altitude and pulmonary arterial hypertension characteristics. METHODS: Forty-two US centers participating in the Pulmonary Hypertension Association Registry enrolled patients who met the definition of WHO Group 1 pulmonary arterial hypertension. We utilized baseline data and patient questionnaire responses. Patients were divided into two groups: moderately high altitude residence (home ≥4000 ft) and low altitude residence (home <4000 ft) based on zip-code. Clinical characteristics, hemodynamic data, patient demographics, and patient reported quality of life metrics were compared. RESULTS: Controlling for potential confounders (age, sex at birth, body mass index, supplemental oxygen use, race, 100-day cigarette use, alcohol use, and pulmonary arterial hypertension medication use), subjects residing at moderately high altitude had a 6-min walk distance 32 m greater than those at low altitude, despite having a pulmonary vascular resistance that was 2.2 Wood units higher. Additionally, those residing at moderately high altitude had 3.7 times greater odds of using supplemental oxygen. CONCLUSION: Patients with pulmonary arterial hypertension who live at moderately high altitude have a higher pulmonary vascular resistance and are more likely to need supplemental oxygen. Despite these findings, moderately high altitude Pulmonary Hypertension Association Registry patients have better functional tolerance as measured by 6-min walk distance. It is possible that a "high-altitude phenotype" of pulmonary arterial hypertension may exist. These findings warrant further study.

Surgical therapies for pulmonary arterial hypertension.

Surgical therapies for the treatment of pulmonary arterial hypertension typically are reserved for patients who are deemed to be refractory to medical therapy and have evidence of progressive right-sided heart failure. Atrial septostomy, a primarily palliative procedure, may stave off hemodynamic collapse from right-sided heart failure long enough to permit a more definitive surgical treatment such as lung or combined heart-lung transplantation. This article discusses indications for and results of atrial septostomy and lung and heart-lung transplantation in patients who have pulmonary arterial hypertension.

Emergency extracorporeal life support for asphyxic status asthmaticus.

We report a case of successful use of extracorporeal life support (ECLS) as salvage treatment in an adult with acute, severe, reversible respiratory failure due to asphyxic status asthmaticus. Conventional measures were ineffective to combat the dynamic hyperinflation; the patient had intrinsic positive end-expiratory pressure > 30 cm H(2)O. We initiated emergency ECLS at the bedside, and after 55 hours of ECLS his respiratory mechanics had markedly improved and he was subsequently weaned off of ECLS and decannulated, without vascular, pulmonary, or neurologic complications. This article reviews the history of ECLS for adult respiratory failure and its application for life-threatening status asthmaticus. This case illustrates the effective use of ECLS for acute respiratory failure due to asphyxic status asthmaticus, and to our knowledge is the first reported case in which the patient's impending cardiopulmonary arrest was due to an unsustainable level of intrinsic positive end-expiratory pressure.

Recommendations for the clinical management of patients receiving macitentan for pulmonary arterial hypertension (PAH): A Delphi consensus document.

In patients treated with macitentan (Opsumit®, Actelion Pharmaceuticals Ltd., Basel, Switzerland) for pulmonary arterial hypertension (PAH), prevention and/or effective management of treatment-related adverse events may improve adherence. However, management of these adverse events can be challenging and the base of evidence and clinical experience for macitentan is limited. In the absence of evidence, consensus recommendations from physicians experienced in using macitentan to treat PAH may benefit patients and physicians who are using macitentan. Consensus recommendations were developed by a panel of physicians experienced with macitentan and PAH using a modified Delphi process. Over three iterations, panelists developed and refined a series of statements on the use of macitentan in PAH and rated their agreement with each statement on a Likert scale. The panel of 18 physicians participated and developed a total of 118 statements on special populations, add-on therapy, drug-drug interactions, warnings and precautions, hospitalization and functional class, and adverse event management. The resulting consensus recommendations are intended to provide practical guidance on real-world issues in using macitentan to treat patients with PAH.

Impact of primary graft failure on outcomes following lung transplantation.

STUDY OBJECTIVES: Primary graft failure (PGF) is a severe acute lung injury syndrome that occurs following lung transplantation. We compared the clinical outcomes of patients who developed PGF with those who did not. METHODS: We conducted a retrospective cohort study including 255 consecutive lung transplant procedures. PGF was defined as (1) diffuse alveolar opacities developing within 72 h of transplantation, (2) an arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio of < 200 beyond 48 h postoperatively, and (3) no other secondary cause of graft dysfunction. PGF was tested for acceptance with 30-day and all-cause hospital mortality rates, overall survival, hospital length of stay (HLOS), duration of mechanical ventilation, and best 6-min walk test (6MWT) distance achieved within 12 months. SETTING: Academic medical center. RESULTS: The overall incidence of PGF was 11.8% (95% confidence interval [CI], 7.9 to 15.9%). The all-cause mortality rate at 30 days was 63.3% in patients with PGF and 8.8% in patients without PGF (relative risk [RR], 7.15; 95% CI, 4.34 to 11.80%; p < 0.001). A total of 73.3% of patients with PGF died during hospitalization vs 14.2% of patients without PGF (RR, 5.18%; 95% CI, 3.51 to 7.63; p < 0.001). The median HLOS in 30-day survivors was 47 days in patients with PGF vs 15 days in those without PGF (p < 0.001), and the mean duration of mechanical ventilation was 15 days in patients with PGF vs 1 day in those without PGF (p < 0.001). By 12 months, a total of 28.5% of survivors with PGF achieved a normal age-appropriate 6MWT distance vs 71.4% of survivors without PGF at 12 months (p = 0.014). The median best 6MWT distance achieved within the first 12 months was 1,196 feet in patients with PGF vs 1,546 feet in those without PGF (p = 0.009). CONCLUSIONS: PGF has a significant impact on mortality, HLOS, and duration of mechanical ventilation following lung transplantation. Survivors of PGF have a protracted recovery with impaired physical function up to 1 year following transplantation.

Ventilator auto-triggering in a patient with tuberculous bronchopleural fistula.

We report a case of ventilator auto-triggering resulting from tuberculous bronchopleural fistula being managed with chest tube suction. Early recognition of bronchopleural fistula-related auto-triggering is extremely important. Auto-triggering can lead to serious adverse effects, including severe hyperventilation and inappropriate escalation of sedatives and/or neuromuscular blockers (administered to reduce spontaneous breathing efforts). Auto-triggering was confirmed in our patient when tachypnea persisted despite pharmacologic neuromuscular paralysis. Auto-triggering can be reduced or eliminated by decreasing ventilator trigger sensitivity or by decreasing the air leak flow by reducing the degree of chest tube suction.

Outcomes using extracorporeal life support for adult respiratory failure due to status asthmaticus.

Our objective was to describe the outcomes for extracorporeal life support (ECLS) use in adult respiratory failure because of status asthmaticus and to determine whether ECLS use in status asthmaticus is associated with greater survival than other indications for ECLS. This retrospective cohort study used the multicenter, International ECLS Organization Registry. The study population included 1,257 adults with respiratory failure requiring ECLS. Status asthmaticus was the primary indication for ECLS in 24 patients. A total of 83.3% of asthmatics survived to hospital discharge compared with 50.8% of nonasthmatics (n=1,233) [odds ratio (OR) favoring survival for asthmatics=4.86, 95% confidence interval (CI) 1.65-14.31, p=0.004]. The survival advantage for asthmatics remained significant after adjustment for potential confounders. Complications were noted in 19 of 24 asthmatics (79.2%). In conclusion, we found that status asthmaticus, as an indication for ECLS in adult respiratory failure, seemed to be associated with greater survival than other indications for ECLS. However, complications are common and whether ECLS confers a survival advantage compared with other salvage treatment options remains unknown. More detailed information and complete reporting of ECLS use for status asthmaticus are needed to determine whether and when the potentially life-saving intervention of ECLS should be initiated in the asthmatic failing conventional therapy.

Wide variation in clinicians' assessment of New York Heart Association/World Health Organization functional class in patients with pulmonary arterial hypertension.

OBJECTIVE: To assess interrater reliability of the New York Heart Association/World Health Organization functional classification as applied by clinicians (defined as both physicians and nurses in this article) to patients with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS: Between March 16 and August 31, 2007, a survey that described 10 hypothetical patients was completed by physicians and nurses attending a conference on PAH. Results were subsequently validated with physicians and nurses who were contacted online through the Pulmonary Hypertension Association. Respondents were asked to assign each patient's functional class as they would normally in clinical practice. RESULTS: The functional class evaluations were completed by 113 clinicians, 87 (77%) of whom had participated in PAH trials; 106 (94%) reported using functional class when determining therapy. Clinicians reported a broad range of factors they considered when evaluating functional class, and their assessments of functional class varied widely. The intraclass correlation coefficient was 0.58 for the initial patient survey and 0.62 for the online survey. At best, one patient was ranked as either class II (by 60 clinicians [53%]) or class III (by 53 [47%]). Clinicians' rankings spanned at least 3 functional classes for each of the other patients. Equally divergent rankings were observed among nurses and physicians. Cluster analysis identified clinicians' tendencies toward "higher" or "lower" functional class rankings. Of the 113 clinicians, 101 (89%) thought that the patients described resembled those seen in their practices. CONCLUSION: Despite the wide use of the New York Heart Association/World Health Organization functional class in clinical care and as a research tool, interrater agreement may be inadequate. Efforts to promote a uniform approach to evaluating functional class might help to standardize PAH care and research.

Coexistent sarcoidosis and HIV infection: an immunological paradox?

The CD4 lymphocyte plays a pivotal role in both sarcoidosis and HIV infection. Caring for a patient with both conditions represents a diagnostic and therapeutic challenge. We describe a patient, previously diagnosed with sarcoidosis, who subsequently contracted HIV infection. Manifestations of sarcoidosis were clinically silent until highly active anti-retroviral therapy was instituted. Her condition improved with the institution of corticosteroids. The diagnostic and therapeutic dilemmas encountered in patients with both conditions will be discussed including a complete review of the literature.

Effects of lung allocation score on waiting list rankings and transplant procedures.

The effect of the new lung allocation score on ranking of patients on the waiting list and the number of transplants performed is not known. We assessed this effect on our lung transplant program and conducted a simulation of lung transplants for the first few months of the new system, using the old waiting lists. Patients with idiopathic pulmonary fibrosis had improved rankings and patients with emphysema had worse rankings, but the number of transplants for each disease category did not change significantly compared with the simulated transplants.