Real-world evidence to advance knowledge in pulmonary hypertension: Status, challenges, and opportunities. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative's Real-world Evidence Working Group.

This manuscript on real-world evidence (RWE) in pulmonary hypertension (PH) incorporates the broad experience of members of the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative Real-World Evidence Working Group. We aim to strengthen the research community's understanding of RWE in PH to facilitate clinical research advances and ultimately improve patient care. Herein, we review real-world data (RWD) sources, discuss challenges and opportunities when using RWD sources to study PH populations, and identify resources needed to support the generation of meaningful RWE for the global PH community.

Sex, Racial, and Geographic Disparities in Pulmonary Embolism-related Mortality Nationwide.

Rationale: Acute pulmonary embolism is a leading cause of cardiovascular death. There are limited data on the national mortality trends from pulmonary embolism. Understanding these trends is crucial for addressing the mortality and associated disparities associated with pulmonary embolism. Objectives: To analyze the national mortality trends related to acute pulmonary embolism and determine the overall age-adjusted mortality rate (AAMR) per 100,000 population for the study period and assess changes in AAMR among different sexes, races, and geographic locations. Methods: We conducted a retrospective cohort analysis using mortality data of individuals aged ⩾15 years with pulmonary embolism listed as the underlying cause of death in the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 2006 to December 2019. These data are produced by the National Center for Health Statistics. Results: A total of 109,992 pulmonary embolism-related deaths were noted in this dataset nationwide between 2006 and 2019. Of these, women constituted 60,113 (54.7%). The AAMR per 100,000 was not significantly changed, from 2.84 in 2006 to 2.81 in 2019 (average annual percentage change [AAPC], 0.2; 95% confidence interval [CI], -0.1 to 0.5; P = 0.15). AAMR increased for men throughout the study period compared with women (AAPC, 0.7 for men; 95% CI, 0.3 to 1.2; P = 0.004 vs. AAPC, -0.4 for women; 95% CI, -1.1 to 0.3; P = 0.23, respectively). Similarly, AAMR for pulmonary embolism increased for Black compared with White individuals, from 5.18 to 5.26 (AAPC, 0.4; 95% CI, 0.0 to 0.7; P = 0.05) and 2.82 to 2.86 (AAPC, 0.0; 95% CI, -0.6 to 0.6; P = 0.99), respectively. Similarly, AAMR for pulmonary embolism was higher in rural areas than in micropolitan and large metropolitan areas during the study period (4.07 [95% CI, 4.02 to 4.12] vs. 3.24 [95% CI, 3.21 to 3.27] vs. 2.32 [95% CI, 2.30-2.34], respectively). Conclusions: Pulmonary embolism mortality remains high and unchanged over the past decade, and enduring sex, racial and socioeconomic disparities persist in pulmonary embolism. Targeted efforts to decrease pulmonary embolism mortality and address such disparities are needed.

Periprocedural Complications With Balloon Pulmonary Angioplasty: Analysis of Global Studies.

BACKGROUND: Balloon pulmonary angioplasty (BPA) was introduced as a treatment modality for patients with inoperable, medically refractory chronic thromboembolic pulmonary hypertension decades ago; however, reports of high rates of pulmonary vascular injury have led to considerable refinement in procedural technique. OBJECTIVES: The authors sought to better understand the evolution of BPA procedure-related complications over time. METHODS: The authors conducted a systematic review of original articles published by pulmonary hypertension centers globally and performed a pooled cohort analysis of procedure-related outcomes with BPA. RESULTS: This systematic review identified 26 published articles from 18 countries worldwide from 2013 to 2022. A total of 1,714 patients underwent 7,561 total BPA procedures with an average follow up of 7.3 months. From the first period (2013-2017) to the second period (2018-2022), the cumulative incidence of hemoptysis/vascular injury decreased from 14.1% (474/3,351) to 7.7% (233/3,029) (P < 0.01); lung injury/reperfusion edema decreased from 11.3% (377/3,351) to 1.4% (57/3,943) (P < 0.01); invasive mechanical ventilation decreased from 0.7% (23/3,195) to 0.1% (4/3,062) (P < 0.01); and mortality decreased from 2.0% (13/636) to 0.8% (8/1,071) (P < 0.01). CONCLUSIONS: Procedure-related complications with BPA, including hemoptysis/vascular injury, lung injury/reperfusion edema, mechanical ventilation, and death, were less common in the second period (2018-2022), compared with first period (2013-2017), likely from refinement in patient and lesion selection and procedural technique over time.

Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a common medical condition associated with increased morbidity and mortality. Through different mechanisms, including passive left-sided congestion and/or vasculopathy, patients with HFpEF can develop pulmonary hypertension (PH). This association -PH-HFpEF- is linked with worsening symptomatology and long-term outcomes. Although pulmonary vasodilators have been effective in treating patients with a pulmonary vasculopathy, such as pulmonary arterial hypertension (PAH), these results have not been replicated in those with PH-HFpEF. There is an unmet need to develop effective medical therapy for this challenging population. In this article, we focus on understanding the definition, epidemiology, diagnosis, clinical implications, and treatment for PH in the setting of HFpEF.

Current status and barriers in pulmonary hypertension care delivery in India: A qualitative analysis.

Although pulmonary hypertension (PH) is widely prevalent in India, care delivery for this condition has unique challenges in a lower middle-income country (LMIC). To describe care delivery for patients with PH and associated barriers in India. We interviewed physicians across eight healthcare systems in India about PH clinical care using semi-structured enquiries to understand care delivery and associated challenges in their specific practice as well as the associated health system. Qualitative analysis was performed using content analysis methodology. Physicians reported that common causes for PH in their practice were rheumatic mitral valve disease, coronary artery disease, and congenital heart disease (CHD). No center had a dedicated PH program. Only one center had a specific protocol for PH management. Diagnostic evaluations were limited, and right heart catheterizations were recommended for patients with CHD. Pulmonary vasodilator therapy was used for severe symptoms or markers of severe disease. Agents used to treat PH were widely variable across physicians and prostacyclins are unavailable in India. Barriers included limited training in PH for physicians, lack of consensus guidelines for PH specific to LMIC, and lack of financial incentives for health care systems to organize dedicated PH programs. Other barriers included poor patient health literacy and socioeconomic barriers that limit ability to test and treat PH. PH care delivery in India is variable with widely differing clinical practices. Dedicated training in PH management and establishing guidelines specific to LMIC like India can form the first step forward.

Considerations for Inotrope and Vasopressor Use in Critically Ill Patients With Pulmonary Arterial Hypertension.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a rare and progressive cardiopulmonary disease, characterized by pulmonary vasculopathy. The disease can lead to increase pulmonary arterial pressures and eventual right ventricle failure due to elevated afterload. The prevalence of PAH in patients admitted to the intensive care unit (ICU) is unknown, and pulmonary hypertension (PH) in the ICU is more commonly the result of left heart disease or hypoxic lung injury (PH due to left heart disease and PH due to lung diseases and/or hypoxia, respectively), as opposed to PAH. Management of patients with PAH in the ICU is complex as it requires a careful balance to maintain perfusion while optimizing right-sided heart function. A comprehensive understanding of the underlying physiology and underlying hemodynamics is crucial for the management of this population. In this review, we summarized the evidence for use of vasopressors and inotropes in the management of PH and extrapolated the data to patients with PAH. We strongly believe that the understanding of the hemodynamic consequences of inotropes and vasopressors, especially from data in the PH population, can lead to better management of this complex patient population.

Performance of the DETECT Algorithm for Pulmonary Hypertension Screening in a Systemic Sclerosis Cohort.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is one of the leading causes of mortality in systemic sclerosis (SSc). This study was undertaken to assess predictive accuracies of the DETECT algorithm and the 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines in SSc patients who underwent right-sided heart catheterization (RHC) for pulmonary hypertension (PH) evaluation. METHODS: Patients with SSc who had diagnostic RHC, had no PH or had PAH, and had available data on variables to allow application of the DETECT and 2015 ESC/ERS guidelines were included for analysis. PH classification was based on hemodynamics using the 2018 revised criteria and extent of lung fibrosis shown on high-resolution computed tomography. Sensitivity and predictive accuracies of the DETECT algorithm and 2015 ESC/ERS guidelines were calculated, including analysis of subjects with a diffusing capacity for carbon monoxide (DLco) of ≥60% predicted. RESULTS: Sixty-eight patients with SSc had RHC, of whom 58 had no PH and 10 had PAH. The mean age was 60.0 years, and 58.8% had limited cutaneous SSc. The DETECT algorithm had a sensitivity of 1.00 (95% confidence interval [95% CI] 0.69-1.00) and a negative predictive value (NPV) of 1.00 (95% CI 0.80-1.00), whereas the 2015 ESC/ERS guidelines had a sensitivity of 0.80 (95% CI 0.44-0.97) and an NPV of 0.94 (95% CI 0.81-0.99). In patients with a DLco of ≥60% (n = 27), the DETECT algorithm had a sensitivity of 1.00 (95% CI 0.29-1.00) and an NPV of 1.00 (95% CI 0.59-1.00), whereas the 2015 ESC/ERS guidelines had a sensitivity of 0.67 (95% CI 0.09-0.99) and an NPV of 0.94 (95% CI 0.71-1.00). CONCLUSION: The DETECT algorithm has high sensitivity and NPV for diagnosis of PAH, including among individuals with a DLco of ≥60%.

Barriers to physical activity in patients with pulmonary hypertension.

Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) have low levels of physical activity (PA). Increased PA has health benefits including improved quality of life. This study aimed to identify patient-perceived barriers to PA that correlate with objectively measured PA in this population. We performed a cross-sectional survey of 40 patients with PAH and CTEPH. Participants rated how often 15 barriers interfere with being physically active on a 5-point Likert Scale. The primary outcome measure was PA quantified using the Fitbit Zip activity tracker for two weeks. The primary independent variables were the 15 barriers and a summary score (total average barriers). Separate multivariable linear regressions were performed to assess the association between the 15 barriers and the summary score and PA adjusting for age, sex, and PAH etiology. Of the participants, 85% (34/40) had valid step counts and were included. Of these 34, 85% (n = 29) were female and 91% (n = 31) had PAH. The median (interquartile range [IQR]) number of daily steps was 3913 (2309-6313). The barriers endorsed most strongly were lack of self-discipline, lack of energy, and lack of interest. In the multivariable analysis, a 1-unit increase in perceived lack of interest, lack of enjoyment, and lack of skills was associated with a significant decrease in step counts of -1414 steps (95% confidence interval [CI] = (-2580 - -248), -1458 steps (-2404 - -511), and -1533 steps (-2910 - -156), respectively. Counseling and interventions aimed at increasing PA in patients with PAH should address interest, enjoyment, and skill development.

Safety of regadenoson stress testing in patients with pulmonary hypertension.

OBJECTIVES: We sought to determine the safety of regadenoson stress testing in patients with PH. BACKGROUND: PH is increasingly recognized at more advanced ages. As many as one-third of patients with PH have coronary artery disease. Because of their physical limitations, patients with PH are unable to adequately exercise. Regadenoson can potentially have an adverse impact due to their tenuous hemodynamics. Current guidelines suggest performing a coronary angiography in patients with PH who have angina or multiple coronary risk factors. METHODS: We identified 67 consecutive patients with confirmed PH by catheterization (mean PA > 25 mmHg not due to left heart disease) who underwent MPI with regadenoson stress. Medical records were reviewed to determine hemodynamic and ECG response to regadenoson. RESULTS: No serious events occurred. Common side effects related to regadenoson were observed, dyspnea being the most common (70.6%). No syncope occurred. Heart rate increased from 74.6 ± 14 to 96.3 ± 18.3 bpm, systolic blood pressure increased from 129.8 ± 20.9 to 131.8 ± 31 mmHg, and diastolic blood pressure decreased from 77.1 ± 11.4 to 72.9 ± 15.3 mmHg. There was no ventricular tachycardia, ventricular fibrillation, or second- or third-degree atrioventricular block. CONCLUSION: Regadenoson stress MPI appears to be well tolerated and safe in patients with PH.

Insuficiencia cardíaca de alto gasto por fístula arterio-venosa congénita: Síndrome de Parkes Weber / High output cardiac failure by congenital arteriovenous fistula: Parkes Weber Syndrome / Insuficiência cardíaca de alto débito por fístula artério-venosa congênita: Síndrome de Parkes Weber

Se presenta el caso de un paciente joven con fístula arterio-venosa congénita en miembro superior derecho, que evoluciona con elefantiasis del miembro afectado, miocardiopatía dilatada e insuficiencia cardíaca de alto gasto. Ante el fracaso del tratamiento quirúrgico (ligadura de la fístula), se decide la embolización percutánea de la misma.

We present a case of a young patient with congenital arteriovenous fistula in the right upper limb, which evolves with elephantiasis of the affected limb, dilated cardiomyopathy and high output heart failure. With the surgical treatment failure (fistula ligation), we decided the fistulas embolization.

Relatamos o caso de um jovem paciente com fístula artério-venosa congênita no membro superior direito, que evolui com elefantíase do membro afetado, cardiomiopatia dilatada e insuficiência cardíaca de alto débito. Com o fracasso do tratamento cirúrgico (ligadura de fistula), decidiu-se a embolização da fístula.