Exploring the patient perspective in pulmonary hypertension.

The global impacts of pulmonary hypertension (PH) were formally recognised in 1973 at the 1st World Health Organization meeting dedicated to primary pulmonary hypertension, held in Geneva. Investigations into disease pathogenesis and classification led to the development of numerous therapies over the ensuing decades. While the impacts of the disease have been lessened due to treatments, the symptoms and adverse effects of PH and its therapies on patients' wellbeing and mental health remain significant. As such, there is a critical need to enhance understanding of the challenges patients face on a global scale with respect to care access, multidimensional patient support and advocacy. In addition, thoughtful analysis of the potential benefits and utilisation of mechanisms for the incorporation of patient-reported outcomes into diagnosis and treatment plans is needed. A summary of these areas is included here. We present a report of global surveys of patient and provider experiences and challenges regarding care access and discuss possible solutions. Also addressed is the current state of PH patient associations around the world. Potential ways to enhance patient associations and enable them to provide the utmost support are discussed. A summary of relevant patient-reported outcome measures to assess health-related quality of life in PH is presented, with suggestions regarding incorporation of these tools in patient care and research. Finally, information on how current global threats such as pandemics, climate change and armed conflict may impact PH patients is offered, along with insights as to how they may be mitigated with advanced contingency planning.

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.

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.

A new day has come: Sotatercept for the treatment of pulmonary arterial hypertension.

Despite increasing therapeutic options and evolving treatment strategies, including targeting 3 therapeutic pathways, in the management of pulmonary arterial hypertension (PAH), morbidity and mortality have remained unacceptably high. Sotatercept is a first-in-class, novel activin signaling inhibitor approved for treating PAH based on evolving efficacy and safety evidence. This state-of-the-art review summarizes the current understanding of the mechanism of action, the impact on outcomes that improve how patients feel, function, and survive, and the safety and adverse event profile to inform readers of this breakthrough novel therapy.

Safety Window for Effective Lesion Crossing in Patients With Chronic Thromboembolic Pulmonary Hypertension.

Background: Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension (CTEPH) is limited by a lack of safe and effective tools for crossing these lesions. We aim to identify a safety window for an intraluminal crossing device in this vascular bed by studying the piercing properties of pulmonary arterial vessel walls and intraluminal CTEPH lesion specimens. As a secondary objective, we also describe the histopathologic features of CTEPH lesions. Methods: Specimens were procured from 9 patients undergoing pulmonary endarterectomy. The specimens were subsampled and identified grossly as arterial wall or intraluminal CTEPH lesions. The force needed for tissue penetration was measured using a 0.38-mm (0.015-in) diameter probe in an ex vivo experimental model developed in our lab. Concurrent histology was also performed. Results: The mean force needed to penetrate the arterial wall and intraluminal CTEPH lesions was 1.75 ± 0.10 N (n = 121) and 0.30 ± 0.04 N (n = 56), respectively (P < .001). Histology confirmed the presence of intimal hyperplasia with calcium and hemosiderin deposition in the arterial wall as well as an old, organized thrombus in the lumen. Conclusions: The pulmonary arterial wall is friable and prone to perforation during instrumentation with workhorse coronary guide wires. However, the results of this study demonstrate that a much lower force is needed for the 0.38-mm (0.015-in) probe to penetrate an intraluminal CTEPH lesion compared to pulmonary arterial intima. This finding suggests the existence of a safety window for lesion-crossing devices, enabling effective balloon pulmonary angioplasty.

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.

Safe and Effective Balloon Pulmonary Angioplasty in the Outpatient Setting: The Michigan Medicine Experience.

Background: Balloon pulmonary angioplasty (BPA) is currently performed at select centers worldwide, with the current standard of practice being postprocedural inpatient monitoring for 24 to 72 hours. We sought to evaluate the safety and efficacy of BPA in a cohort of patients with chronic thrombo-embolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH) and outline a protocol for implementation in the outpatient setting. Methods: All patients with distal, inoperable CTEPH, residual symptoms after pulmonary endarterectomy, or symptomatic CTEPD from July 1, 2020, to June 30, 2022, were evaluated by a multidisciplinary chronic thromboembolic pulmonary hypertension team for consideration of BPA. Patients undergoing each BPA session adhered to a regimented protocol developed and implemented at our institution. Safety and efficacy were retrospectively evaluated with a mean follow-up time of 8.5 months. Results: Eighteen patients underwent a total of 78 BPA sessions. Overall, there was a significant improvement in World Health Organization functional class and mean improvement in 6-minute walking distance of +67 m. Hemodynamic parameters significantly improved with a mean decrease in mean pulmonary artery pressure and pulmonary vascular resistance of 7.3 ± 5.8 mm Hg and 1.7 ± 1.5 Wood units, respectively (P <.05). Complication rates were low with 3 (3.9%) of 78 patients developing scant hemoptysis and 1 (1.3%) of 78 experiencing vascular injury requiring inpatient hospitalization. Conclusions: BPA is both safe and effective when implemented in the outpatient setting using a regimented protocol provided there are necessary contingencies in place.

Symptoms Suggestive of Postpulmonary Embolism Syndrome and Utilization of Diagnostic Testing.

Background: Persistent symptoms of chest pain, dyspnea, fatigue, lightheadedness, and/or syncope more than 3 months after an acute pulmonary embolism (PE) are collectively classified as postpulmonary embolism syndrome (PPES). Although PPES is increasingly recognized as an important long-term sequel of acute PE, its contemporary incidence is unclear. Furthermore, the utilization of diagnostic testing for further phenotypic characterization of these patients is unknown. This study aimed to define the incidence of PPES and evaluate the utilization of diagnostic tests among a national cohort of patients with PE. Methods: Retrospective cohort study was performed using the national administrative database, Clinformatics DataMart Database (Optum Insight), and included adult patients (18 years or older) with no history of acute PE or pulmonary hypertension, diagnosed with acute PE between October 1, 2016, and December 31, 2018. With acute PE event as the exposure, the incidence of symptoms consistent with PPES and diagnostic test utilization among patients with PPES were evaluated. Results: Of 21,297 incident patients with acute PE, 11,969 (56.2%) showed ≥1 symptom of PPES, which was new since their pre-PE baseline. New dyspnea was the most common and noted in 3268/15,203 (21.5%) patients, followed by new malaise or fatigue in 2894/15,643 (18.5%) patients. Among the 11,969 patients with PPES, 5128 (42.8%) received ≥1 diagnostic test, with 3242 (27%) receiving a computed tomography pulmonary angiogram, 2997 (25%) receiving an echocardiogram, and 325 (2.7%) received a ventilation-perfusion scan within 3-12 months after PE. Significantly lower use of diagnostic testing was noted in patients older than 65 years (adjusted odds ratio, 0.89; 95% CI, 0.81-0.98). Conclusions: Symptoms consistent with PPES are common after acute PE, occurring in more than half of the patients. Diagnostic imaging for further phenotypic characterization is used in less than half of such patients with PPES.

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.

Anatomical Variations in Pulmonary Arterial Branches in Patients Undergoing Evaluation for Chronic Thromboembolic Pulmonary Hypertension.

Background: Catheter-based interventions have emerged for both acute and chronic pulmonary thromboembolic disease. With this development and the need for segmental cannulation, anatomic understanding of pulmonary arterial segmental branch origination is important. We aim to describe the prevalence of different pulmonary arterial segmental branch origination patterns. Methods: This study included 179 consecutive patients who underwent bilateral nonselective invasive pulmonary angiography for the evaluation of chronic thromboembolic pulmonary hypertension. Results: In our study population (age, 59.0 ± 14.8 years, 55.3% female, 71% White), we found several anatomic variations of branches to the different lobes. These included 7 branching patterns in the right upper lobe, 3 in the right middle lobe, and 10 in the right lower lobe (4 patterns for the origin of the superior segmental artery and 6 for the origin of the basilar segmental arteries). On the left side, we found 8 patterns in the left upper lobe, with 5 involving lingular branches, and 9 in the left lower lobe (5 for the origin of the superior segmental artery and 4 for the basilar segmental pulmonary arteries). Although there were many variations, only 2-3 variations for each individual lobe accounted for >90% of the angiograms. Conclusions: Up to 3 anatomic branching patterns per lobe were noted to account for >90% of pulmonary artery branching variations in this study. This knowledge is not only useful for the interventionalist performing catheter-directed therapies but also for future research efforts that aim to standardize reporting of pulmonary angiographic findings.

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.

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.

Interventional Imaging Roadmap to Successful Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension.

Balloon pulmonary angioplasty (BPA) is an evolving treatment modality for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not candidates for pulmonary endarterectomy. Although several imaging modalities currently exist for evaluating CTEPH, their individual use, specifically in the clinical practice of BPA, has not been well described. In this article, we provide a preprocedural, intraprocedural, and postprocedural interventional imaging roadmap for safe and effective BPA performance in routine clinical practice. Preprocedural assessment includes transthoracic echocardiography for right ventricular assessment, ventilation/perfusion scan to identify pulmonary segments with the highest degree of hypoperfusion, cross-sectional chest imaging excluding alternative causes of mismatched defects and providing anatomic and perfusion imaging concurrently, and nonselective invasive pulmonary angiography for risk stratification of individual lesion subtypes. Intraprocedural assessment includes subselective segmental angiography (SSA) for delineating segmental and subsegmental branch anatomy, lesion identification, and vessel sizing. Intravascular ultrasound and optical coherence tomography serve as adjunctive intraprocedural tools for more accurate vessel sizing and lesion characterization when SSA alone is insufficient. Postprocedural considerations include chest radiography to monitor for immediate postprocedure complications and echocardiography for the interval assessment of the right ventricle on longer-term follow-up.

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.

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.