Novel Drugs for the Treatment of Pulmonary Arterial Hypertension: Where Are We Going?

Pulmonary arterial hypertension (PAH) is a progressive disease that despite advances in therapy is associated with a 7-year survival of approximately 50%. Several risk factors are associated with developing PAH, include methamphetamine use, scleroderma, human immunodeficiency virus, portal hypertension, and genetic predisposition. PAH can also be idiopathic. There are traditional pathways underlying the pathophysiology of PAH involving nitric oxide, prostacyclin, thromboxane A2, and endothelin-1, resulting in impaired vasodilation, enhanced vasoconstriction and proliferation in the pulmonary vasculature. Established PAH medications targets these pathways; however, this paper aims to discuss novel drugs for treating PAH by targeting new and alternative pathways.

Pulmonary Hypertension Association's 2022 International Conference Scientific Sessions Overview.

The considerable progress made in recent years in the diagnosis, risk stratification, and treatment of pulmonary hypertension was highlighted during the most recent edition of the Pulmonary Hypertension Association Scientific Sessions, which was held in Atlanta, Georgia from June 9 to 11, 2022, with the theme: Vision for the PHuture: The Evolving Science and Management of PH. Content presented over the 3-day conference focused on scientific and management updates since the last sessions were held in 2018 and included didactic talks, debates, and roundtable discussions across a broad spectrum of topics related to pulmonary hypertension. This article aims to summarize the key messages from each of the session talks.

Characteristics of Patients With Pulmonary Arterial Hypertension in a Pulmonary Hypertension Association-Accredited Comprehensive Care Center: A Contrast in Features When Compared With US National Registry Data.

Background Since the initial description in the 1980s, our understanding of the diversity of pulmonary arterial hypertension (PAH) has continued to evolve. In this study, we report the characteristics of patients seen in an academic medical center for PAH from August 2020 through November 2021 and contrast those with nationally reported data from the United States Pulmonary Hypertension Scientific Registry (USPHSR).  Study Design Investigators at the University of Utah Pulmonary Hypertension Program prospectively enrolled adult patients diagnosed with WHO Group 1 PAH, who were evaluated between August 2020 and November 2021 in a program-specific registry. Patient exposure and health histories were collected through structured interviews and questionnaires, along with clinical data and medication use. A total of 242 patients were enrolled in the University of Utah Pulmonary Hypertension Registry (UUPHR).  Results Of the 242 enrolled patients, the most common etiology was associated PAH (APAH), accounting for 71.1% of the population. The second largest etiology was idiopathic PAH (IPAH) at 26.4%. The remaining patients were distributed between familial PAH (FPAH), pulmonary veno-occlusive disease (PVOD), and others. Of the total population classified as APAH, 39% of cases were noted as secondary to connective tissue disease (CTD) and 33% as toxin-induced. These represented 28% and 24% of the total population, respectively.  Conclusions In this US-based accredited academic medical center, the etiology of PAH in our patient population contrasts with national registry data. In the UUPHR, APAH, specifically CTD-PAH and toxin-associated PAH, accounts for the majority of patients with PAH. This contrasts with IPAH, which nationally is the most reported cause of PAH. Differences in our population may reflect the regional variation of the referral site, but it is noteworthy for its contrast with historically reported phenotypes.

Imaging in Pulmonary Vascular Disease-Understanding Right Ventricle-Pulmonary Artery Coupling.

The right ventricle (RV) and pulmonary arterial (PA) tree are inextricably linked, continually transferring energy back and forth in a process known as RV-PA coupling. Healthy organisms maintain this relationship in optimal balance by modulating RV contractility, pulmonary vascular resistance, and compliance to sustain RV-PA coupling through life's many physiologic challenges. Early in states of adaptation to cardiovascular disease-for example, in diastolic heart failure-RV-PA coupling is maintained via a multitude of cellular and mechanical transformations. However, with disease progression, these compensatory mechanisms fail and become maladaptive, leading to the often-fatal state of "uncoupling." Noninvasive imaging modalities, including echocardiography, magnetic resonance imaging, and computed tomography, allow us deeper insight into the state of coupling for an individual patient, providing for prognostication and potential intervention before uncoupling occurs. In this review, we discuss the physiologic foundations of RV-PA coupling, elaborate on the imaging techniques to qualify and quantify it, and correlate these fundamental principles with clinical scenarios in health and disease. © 2022 American Physiological Society. Compr Physiol 12: 1-26, 2022.

Left Heart Disease-Related Pulmonary Hypertension.

Pulmonary hypertension (PH) due to left heart disease (LHD; group 2 PH) is a common complication of heart failure with reduced ejection fraction and heart failure with preserved ejection fraction and is often related to disease severity and duration of these diseases. PH due to LHD is associated with negative impact on outcomes in addition to worse symptoms and exercise capacity. Risk factors for group 2 PH are older age, hypertension, atrial fibrillation, and features of metabolic syndrome. The main mechanisms for group 2 PH are believed to be vascular remodeling secondary to sustained elevated intravascular pressure.

Preference of sweeteners among Saudi diabetes patients from a tertiary health care centre in Riyadh, Saudi Arabia.

BACKGROUND: Choice of sweetening options can influence glyceamic control among patients with diabetes. This study aims to investigate the preference of added sweeteners for Saudi patients with diabetes, factors associated with the choice of sweeteners and the attitude of the patients towards the use of artificial sweeteners. METHODS: This was a cross-sectional study conducted at King Saud University Medical City in Riyadh, Saudi Arabia and targeting Saudi patients with type 2 diabetes mellitus. Data was collected via personal interviews accessing medical records of interviewed patients. Patients were asked about consumption of sweeteners and types of consumed soft drinks on daily basis. Bi-variate analysis of the associations between choice of sweeteners and patients characteristics was performed and followed by binary logistic regression to adjust for potential confounders such as age, gender, and education level. RESULTS: A total of 302 Saudi diabetic patients were recruited in this investigation. Among this sample, frequency of patients reporting weekly consumption of white sugar was the highest (57%), followed by honey (26%) and artificial sweeteners (12% for powder form and 10.5% for tablets). Consumption of white sugar was significantly more frequent among patients with higher level of Body Mass Index (BMI) (P value < 0.05). The frequency of using honey was higher among females while consumption of either sugared or low calorie soft drinks was significantly higher among male patients (P values < 0.05). Upon asking the patients about their attitude towards artificial sweeteners, only 25% of the sample agreed that their use can aid in reduction of caloric intake while 35% of the sample agreed that artificial sweeteners can be harmful to the body. CONCLUSIONS: Among this sample of type 2 diabetes patients, the frequency of white sugar and honey use as a sweetening option is high. These findings generate the need for further research to investigate the effectiveness of health education and nutritional advice among diabetes patients attending similar clinical settings in Saudi Arabia.

Diabetes and driving recommendations among healthcare providers in Saudi Arabia. A significant gap that requires action.

OBJECTIVES: To assess healthcare providers' knowledge and awareness of the recommendations for drivers with insulin-treated diabetes in Saudi Arabia. Methods: A cross-sectional study was conducted among healthcare providers working at 4 tertiary hospitals in Riyadh, Saudi Arabia between April 2016 and December 2016 using a self-administered questionnaire. Results: A total of 285 healthcare providers completed the survey (response rate 88.5%). Most (70.2%) were aware of the safe driving recommendations for patients with insulin-treated diabetes. However, the need to check blood glucose levels before driving was underestimated by almost one-third (30.2%). Only one-quarter (24.6%) identified the correct level of blood glucose level that is safe for a patient when driving, and 28.4% identified the recommended time for checking blood glucose before driving. Participants who were aware of the recommendations for safe driving had a significantly higher average knowledge score (68.8%) than those who were not aware (58.8%; p less than 0.001). There was a significant difference in the average knowledge score among medical specialties (p=0.002) and job levels (p less than 0.001). Conclusions: Most healthcare providers identified the importance of evaluating their patients for ability to drive safely, but we found some important areas of knowledge deficit. Professional intervention to improve healthcare providers' awareness and knowledge regarding diabetes and driving is the first step in improving detection and reporting high-risk drivers with diabetes to prevent future driving mishaps.

Patterns and determinants of stress among consultant physicians working in Saudi Arabia.

BACKGROUND: Physicians experience several work-related stressors that have been mounting up in recent decades. This study aimed to examine perceived stress and its risk factors and consequences among consultant physicians in Saudi Arabia. METHODS: A cross-sectional study was conducted from November 2014 to March 2015 among physicians who were assigned rank of consultant. The stress level was assessed using perceived stress scale (PSS). RESULTS: A total of 582 consultants participated. The average age was 46.9±7.9 years, 71% were males, 56% were Saudi, 15% were smokers, and 68% slept ≤6 hours per night. The median PSS score was 17 (interquartile range of 14-21), which represented 44% of maximum possible PSS score. The upper tertile of PSS score (represents a high stress level) was significantly associated with being younger, female, and Saudi. The majority (85%) considered job environment to be stressful and ~50% attributed that to a high workload and a noncooperative administration. In the year preceding this study, half of consultants frequently contemplated or even worked toward changing their medical institutes or even moving to work outside Saudi Arabia because of perception of a stressful working environment. Over the previous year, encountering life stressors, considering job environment as stressful and experiencing passive suicidal ideation, were significantly associated with higher levels of stress. In multivariate analysis, the following factors were independently associated with stress: female gender (odds ratio [OR]=2.41, 95% CI 1.58-3.70) and perceived stressful working environment (OR=3.66, 95% CI 1.87-7.17). CONCLUSION: Consultant physicians in Saudi Arabia experience moderate to high levels of perceived stress that are relatively comparable to physicians worldwide. A significant association was found between stress levels and both female gender and perception of a stressful working environment. Further studies are required to assess physician-based interventions and organization-directed approaches to management of stress among physicians.