Hypertension Experts Research Articles

Abstract P117: Provider Concordance to the Current 2017 High Blood Pressure (BP) Clinical Practice Guidelines and Patient Blood Pressure Control

Introduction: The AHA/ACC 2017 High BP guidelines introduced key changes, compared to previous guidelines, including a new hypertension definition (≥130/80 mm Hg) and lower medication thresholds for patients at cardiovascular risk. The impact of provider adherence to these guidelines on patient BP control has not been fully explored. Methods: We identified 3,749 new stage 1 hypertension patients (7,214 visits) and 11,013 new stage 2 hypertension patients (33,321 visits), aged ≥18, from the Vanderbilt University Medical Center database. We scrutinized outpatient BP levels, prescribed medications, follow-up visits, lab results, demographics, comorbid conditions, and physician notes from January 2018 to December 2022. This data was compared to hypertension treatment criteria developed from the 2017 guidelines that was validated by six hypertension experts. Active primary care patients (with 1 visit per year) were included. Mixed-effects Poisson regression and mixed-effects linear regression examined the relationship between guideline adherence and controlled BP (<130/80 mm Hg) and continuous BP, respectively. Results: Among stage 1 hypertension visits, 12.2% were treated with at least one antihypertensive drug according to guidelines, resulting in a 13% increase in BP control and a reduction in systolic BP by 2.02 mm Hg. For stage 2 hypertension visits, 26% received treatment with at least two first-line antihypertensive drug classes, leading to a 45% increase in BP control and reductions in systolic and diastolic BP by 3.79 mm Hg and 1.93 mm Hg, respectively. No significant difference in BP control was observed among stage 2 patients treated with two versus one first-line drug. Adherence to follow-up guidelines resulted in a 24% improvement in BP control for stage 1 patients and stage 2 patients when their follow-up visit occurred within 1 month. Subsequent follow-up visits within 1-month improved BP control by 34% if BP was not controlled previously. Additionally, 42.4% of patients with uncontrolled BP for 1 month received an increase in medication dose or a change/addition of medication class and showed a 7% increase in BP control within next month. Conclusion: Provider adherence to recommended antihypertensive drug treatment guidelines (12%-26%), follow-up assessments guidelines (29%-37%), and treatment intensification (42.4%) were poor. However, patients treated according to the guidelines showed significant improved BP control.

A roadmap for clinical trials in MASH-related compensated cirrhosis.

Although metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of cirrhosis worldwide, therapeutic options are limited and the number of clinical trials in MASH-related compensated cirrhosis is low as compared to those conducted in earlier disease stages. Moreover, designing clinical trials in MASH cirrhosis presents a series of challenges regarding the understanding and conceptualization of the natural history, regulatory considerations, inclusion criteria, recruitment, end points and trial duration, among others. The first international workshop on the state of the art and future direction of clinical trials in MASH-related compensated cirrhosis was held in April 2023 at Vall d'Hebron University Hospital in Barcelona (Spain) and was attended by a group of international experts on clinical trials from academia, regulatory agencies and industry, encompassing expertise in MASH, cirrhosis, portal hypertension, and regulatory affairs. The presented Roadmap summarizes important content of the workshop on current status, regulatory requirements and end points in MASH-related compensated cirrhosis clinical trials, exploring alternative study designs and highlighting the challenges that should be considered for upcoming studies on MASH cirrhosis.

Translation, adaptation, and validation of a Chinese version of the Hypertension Self-Care Activity Level effects (H-SCALE) for patients with hypertension.

Lifestyle modification is an essential component of prevention and management of hypertension. Existing instruments in Taiwan focus on assessing lifestyle modifications by evaluating medication adherence or confidence in controlling blood pressure. However, other self-care activities, such as diet, physical activity, weight management, smoking, and alcohol consumption are also important. The Hypertension Self-Care Activity Level Effects (H-SCALE) is one such instrument, but there are no similar tools available in Taiwan. This study aimed to translate the H-SCALE into Chinese and test its validity, and reliability in a sample of adults with hypertension. The English version of the 31-item H-SCALE was translated into Chinese using the forward-backward method. The content validity index (CVI) of the translated scale was determined by five experts in hypertension. Item analysis was conducted with a pilot sample of 20 patients with hypertension. Cronbach's α was used to establish the internal consistency reliability for the Chinese version of the H-SCALE (H-SCALE-C). Exploratory factor analysis (EFA) explored the structure of the H-SCALE-C. Additionally, construct validity was examined with confirmatory factor analysis (CFA). Patients with hypertension were recruited by convenience sampling from a cardiovascular outpatient clinic of a medical center in northern Taiwan. A total of 318 patients met the inclusion criteria and participated in factor analysis in the study. Pilot testing of the scale items indicated most patients could not accurately estimate the number of days of alcohol consumption for the previous week. Therefore, three alcohol-related items were removed. The adaptation resulted in a 28-item H-SCALE-C. EFA revealed a 4-factor solution with 13 items that explained 63.93% of the total variance. CFA indicated a good fit for a 4-factor model and construct validity was acceptable. Internal consistency reliability was acceptable (Cronbach's alpha for the four subscales ranged from 0.65 to 0.94). Convergent validity was acceptable, and discriminant validity was significant. The H-SCALE-C is a valid, reliable tool for promptly assessing life-style activities for patients with hypertension in Taiwan. The instrument is suitable for assisting healthcare providers in evaluating self-care activities, which could be used to facilitate lifestyle modifications for patients with hypertension.

Familial hyperaldosteronism: an European Reference Network on Rare Endocrine Conditions clinical practice guideline.

We describe herein the European Reference Network on Rare Endocrine Conditions clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, paediatric endocrinology, and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series. The guideline includes a brief description of the genetics and molecular pathophysiology associated with each condition, the patients to be screened, and how to screen. Diagnostic and treatment approaches for patients with genetically determined diagnosis are presented. The recommendations apply to patients with genetically proven familial hyperaldosteronism and not to families with more than one case of primary aldosteronism without demonstration of a responsible pathogenic variant.

The effect of sildenafil on maternal mortality in pulmonary arterial hypertension associated with congenital heart disease

Abstract Background Maternal mortality in pulmonary arterial hypertension (PAH) is very high, around 30–56%, so that patients with PAH and congenital heart disease (CHD) are advised to prevent pregnancy with class I-C recommendations. If the pregnancy continues, it must be handled by a multidisciplinary team with pulmonary hypertension (PH) experts, at the PH referral center. One of the PH-specific drug included in the FDA criteria B for pregnant women available in Indonesia is sildenafil. Sildenafil was reported to improve clinical symptoms and pregnancy outcomes in pregnant women with mild-moderate PAH. Sildenafil also had a tendency to reduce all-cause mortality although it was not statistically significant. Pulmonary hypertension specific drugs could reduce maternal mortality15.8% in subjects with PAH. However, research on sildenafil in maternal clinical outcomes is still very limited. Purpose This study aims to determine the effect of sildenafil on maternal mortality with PAH associated with CHD. Methods This study is an analytic observational study with a retrospective cohort method. Patient data were taken from the maternal registry, the Congenital HeARt Disease in adult and Pulmonary Hypertension (COHARD-PH) registry, and from the medical records of our general hospital who met the research criteria from August 2015 to December 2022. We assess the effect of sildenafil compared with controlled (without sildenafil) group. The clinical outcome of the study was maternal death during pregnancy and/or after delivery up to 42 days due to all causes (all causes mortality). Results Of 68 pregnant women who met the inclusion and exclusion criteria there were 32 subjects in the sildenafil group and 36 subjects in the control group. Maternal mortality was found to be higher (17.6%) in the group without sildenafil vs 9.7% in the sildenafil group. The majority causes of death were HP crisis (7 patients), 1 patient died from thromboembolism (HELLP syndrome), and 1 patient died from massive bleeding due to retained placenta. In the bivariate analysis, it was found that the NYHA functional class had a significant effect on maternal mortality with a p value <0.05, but not significantly from multivariate analysis. In the bivariate and multivariate analysis, general anesthesia had a statistically significant effect on maternal mortality with p=0.018. Of the 9 pregnant women who died, 5 patients received general anesthesia. Of the five patients, NYHA III-IV was found in 4 subjects (4/5 = 80%) and the other patient was NYHA II but subject came in at 63% saturation. All of the subjects are Eisenmeinger syndrome. Conclusion Sildenafil can reduce maternal mortality by 45% although it is not statistically significant. Further studies with larger data are needed to confirm this result.Basic Characteristics of SubjectsRelationship of Sildenafil with Maternal

Italian Society of Interventional Cardiology (GISE) and Italian Society of Arterial Hypertension (SIIA) Consensus document on the role of renal denervation in the management of the difficult to treat hypertension

Arterial hypertension is the most prevalent cardiovascular risk factor worldwide. Despite the availability of many and effective antihypertensive medications, the prevalence of uncontrolled blood pressure (BP) remains high. As sympathetic hyperactivity has long been recognized as a major contributor to resistant hypertension, catheter-based renal denervation (RDN) has emerged as a new strategy to reduce BP. RDN aims to interrupt the activity of renal sympathetic nerves by applying radiofrequency (RF) energy, ultrasound (US) energy, or injection of alcohol in the perivascular space. The Symplicity HTN-3 trial, the largest sham-controlled trial using the first-generation RF-based RDN device, failed to significantly reduce BP. Since then, new devices and techniques have been developed and consequently many sham-controlled trials using second-generation RF or US-based RDN devices have demonstrated the BP lowering efficacy and safety of the procedure. A multidisciplinary team involving hypertension experts, interventionalists with expertise in renal interventions and anesthesiologists, plays a pivotal role from the selection of the patient candidate for the procedure to the post-procedural care. The aim of this consensus document is to summarize the current evidence about the use of RDN in difficult to treat hypertension and to propose a management strategy from the selection of the patient candidate for the procedure to the post-procedural care.

Implementation Strategies to Improve Blood Pressure Control in the United States: A Scientific Statement From the American Heart Association and American Medical Association.

Hypertension is one of the most important risk factors that contribute to incident cardiovascular events. A multitude of US and international hypertension guidelines, scientific statements, and policy statements have recommended evidence-based approaches for hypertension management and improved blood pressure (BP) control. These recommendations are based largely on high-quality observational and randomized controlled trial data. However, recent published data demonstrate troubling temporal trends with declining BP control in the United States after decades of steady improvements. Therefore, there is a widening disconnect between what hypertension experts recommend and actual BP control in practice. This scientific statement provides information on the implementation strategies to optimize hypertension management and to improve BP control among adults in the United States. Key approaches include antiracism efforts, accurate BP measurement and increased use of self-measured BP monitoring, team-based care, implementation of policies and programs to facilitate lifestyle change, standardized treatment protocols using team-based care, improvement of medication acceptance and adherence, continuous quality improvement, financial strategies, and large-scale dissemination and implementation. Closing the gap between scientific evidence, expert recommendations, and achieving BP control, particularly among disproportionately affected populations, is urgently needed to improve cardiovascular health.

Renal Denervation as a Complementary Treatment Option for Uncontrolled Arterial Hypertension: A Situation Assessment.

Uncontrolled arterial hypertension is a major global health issue. Catheter-based renal denervation has shown to lower blood pressure in sham-controlled trials and represents a device-based, complementary treatment option for hypertension. In this situation assessment, the authors, who are practicing experts in hypertension, nephrology, general practice and cardiology in the Republic of Ireland, discuss the current evidence base for the BP-lowering efficacy and safety of catheter-based renal denervation with different modalities. Although important questions remain regarding the identification of responders, and long-term efficacy and safety of the intervention, renal denervation has the potential to provide much-needed help to address hypertension and its adverse consequences. The therapeutic approach needs to be multidisciplinary and personalised to take into account the perspective of patients and healthcare professionals in a shared decision-making process.

Requirements for design and function of blood pressure measuring devices used for the management of hypertension: Consensus Statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular variability and STRIDE BP.

To develop scientific consensus recommendations for the optimal design and functions of different types of blood pressure (BP) measuring devices used in clinical practice for the detection, management, and long-term follow-up of hypertension. A scientific consensus meeting was performed by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability and STRIDE BP (Science and Technology for Regional Innovation and Development in Europe) during the 2022 Scientific Meeting of the ESH in Athens, Greece. Manufacturers were also invited to provide their feedback on BP device design and development. Thirty-one international experts in clinical hypertension and BP monitoring contributed to the development of consensus recommendations on the optimal design of BP devices. International consensus was reached on the requirements for the design and features of five types of BP monitors, including office (or clinic) BP monitors, ambulatory BP monitors, home BP monitors, home BP telemonitors, and kiosk BP monitors for public spaces. For each device type "essential" requirements (must have), and "optional" ones (may have) are presented, as well as additional comments on the optimal device design and features. These consensus recommendations aim at providing manufacturers of BP devices with the requirements that are considered mandatory, or optional, by clinical experts involved in the detection and management of hypertension. They are also directed to administrative healthcare personnel involved in the provision and purchase of BP devices so that they can recommend the most appropriate ones.

ERECTILE DYSFUNCTION IN HYPERTENSIVE PATIENTS: SCREENING AND MANAGEMENT BY GENERAL PRACTITIONERS IN FRANCE

Objective: Non-compliance remains one of the main factors of poor blood pressure control in France and worldwide. Erectile dysfunction (ED), a cardiovascular risk factor (CVRF), is common in hypertensive patients. The general practitioner (GP) is in the front line in the management of hypertension and is often the first point of contact in the event of ED. To review the knowledge and practices of a sample of French GPs to promote the French Society of Hypertension (SFHTA) expert consensus on ED in hypertensive patients. Design and method: Descriptive observational study, carried out in a declarative mode via a Google Forms questionnaire distributed to 102 GPs practicing in Seine-St-Denis. Results: GPs (94,1 %) didn’t know the French Expert Consensus of the SFHTA, regardless their age or their mode of exercise. Only 10% of the GPs talked about ED with their patient regularly, whereas 68.6% of them declared to be comfortable discussing sexuality. GPs recognized ED as CVRF marker and were aware of possible side effects of the antihypertensive treatment on sexual function of their patient. However, the GPs were divided on the fact of warning the patients of the possible side effect of the treatments. Conclusions: Beyond the fact that the French Expert Consensus of the SFHTA concerning ED in hypertensive patients (2018) is not known in GPs, this work also highlights the difficulty of addressing the subject in consultation. Not prescribing beta-blockers in hypertensive patients (without any other indication) and identifying hypertensive patients with CVRF a fortiori with several drug classes are key elements for the best management of ED and combat non-compliance in hypertension.

Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice. This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision-making process should take (i) the patient's global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure. Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.

Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice. This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision-making process should take (i) the patient's global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure. Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.

S-45-1: ONCO-HYPERTENSION: CONCEPT AND FUTURE PERSPECTIVES

In these decades, the morbidity of cancer has been increasing worldwide. On the other hand, the development of cancer treatment, such as small-molecule inhibitors, had improved the prognosis of patients with cancer. Consequently, cardiovascular diseases in cancer-survivors have become a matter of global concern. As a matter of fact, the mortality from cardiovascular events surpasses the mortality from cancers themselves in several types of cancer. Hypertension is reported to be the most frequent comorbidity and a significant risk factor for cardiovascular diseases among cancer-survivors. Besides, many types of newly discovered small-molecule inhibitors, including vascular endothelial growth factor signaling pathway inhibitors, proteasome inhibitors and Bruton-type tyrosine kinase inhibitors have been reported to be associated with blood pressure elevation. On the other hand, there have been reports that hypertension itself is associated with the occurrence of certain types of cancer, such as kidney or colon cancer, and some researchers have raised the possibility that antihypertensive drugs, such as thiazide diuretics, could elevate the risk of skin cancer from cancer registry database. From these, there is a close relationship between hypertension and cancers. However, many issues have remained to be solved regarding this field. For example, few guidelines mentioned the optimal target blood pressure and appropriate types of antihypertensive drugs during and after cancer therapy. Indeed, cancer patients are excluded from major large-scale trials evaluating the effects of antihypertensive drugs, and the patients with cardiovascular diseases are excluded from trials studying the effect of anticancer therapy, which makes it difficult to draw a definite conclusion regarding these issues. Additionally, it has not been clarified whether hypertension itself or the use of antihypertensive drugs are real risk factors for certain types of cancer and the screening for cancer occurrence is necessary for patients with hypertension or antihypertensive drugs. From these, we have been proposed a new concept, Onco-Hypertension, to better understand the complex association between hypertension and cancer. The concept, Onco-Hypertension, not only covers experimental and clinical studies exploring the bidirectional association between hypertension and cancer but also pursues comprehensive management of hypertensive cancer patients to improve their prognosis and quality of life. We think that multidisciplinary team approach including experts in hypertension, oncology, cardiology, nursing and so on, is necessary to clarify the unsolved issues regarding this, Onco-Hypertension, field.

Provider Perspectives on Patient- and Provider-Facing High Blood Pressure Clinical Decision Support.

Hypertension, persistent high blood pressures (HBP) leading to chronic physiologic changes, is a common condition that is a major predictor of heart attacks, strokes, and other conditions. Despite strong evidence, care teams and patients are inconsistently adherent to HBP guideline recommendations. Patient-facing clinical decision support (CDS) could help improve recommendation adherence but must also be acceptable to clinicians and patients. This study aimed to partly address the challenge of developing a patient-facing CDS application, we sought to understand provider variations and rationales related to HBP guideline recommendations and perceptions regarding patient role and use of digital tools. We engaged hypertension experts and primary care respondents to iteratively develop and implement a pilot survey and a final survey which presented five clinical cases that queried clinicians' attitudes related to actions; variations; prioritization; patient input; importance; and barriers for HBP diagnosis, monitoring, and treatment. Analysis of Likert's scale scores was descriptive with content analysis for free-text answers. Fifteen hypertension experts and 14 providers took the pilot and final version of the surveys, respectively. The majority (>80%) of providers felt the recommendations were important, yet found them difficult to follow-up to 90% of the time. Perceptions of relative amounts of patient input and patient work for effective HBP management ranged from 22 to 100%. Stated reasons for variation included adverse effects of treatment, patient comorbidities, shared decision-making, and health care cost and access issues. Providers were generally positive toward patient use of electronic CDS applications but worried about access to health care, nuance of recommendations, and patient understanding of the tools. At baseline, provider management of HBP is heterogeneous. Providers were accepting of patient-facing CDS but reported preferences for that CDS to capture the complexity and nuance of guideline recommendations.

Blood pressure telemonitoring and telemedicine for hypertension management—positions, expectations and feasibility of Latin–American practitioners. SURVEY carried out by several cardiology and hypertension societies of the Americas

Purpose To assess the opinion of Latin–American physicians on remote blood pressure monitoring and telehealth for hypertension management. Material and methods Cross-sectional survey of physicians residing in Latin–America. The study was conducted by the Mexico Hypertension Experts Group, Interamerican Society of Hypertension, Interamerican Society of Cardiology Epidemiology and Cardiovascular Prevention Council, and National Cardiologist Association of Mexico. An online survey composed of 40 questions using Google Forms was distributed from 7 December 2021, to 3 February 2022. The survey was approved by the GREHTA Ethics Committee and participation was voluntary and anonymous. Multiple logistic regression models were constructed to identify the challenges of telehealth. Results 1753 physicians’ responses were gathered. The responses came from physicians from different Latin–American countries, as follows: 24% from Mexico, 20.6% from Argentina, 14.7% from Colombia, 10.9% from Brazil, 8.7% from Venezuela, 8.2% from Guatemala and 3.2% from Paraguay. Responders with a high interest in carrying out their assistance task through remote telemonitoring reached 48.9% (821), while 43.6% are already currently conducting telemonitoring. A high number, 62%, claimed to need telemonitoring training. There is a direct relation between higher interest in telemonitoring and age, medical specialty, team working, residence in the biggest cities, expectations regarding telemedicine and reimbursement. Conclusions Remote monitoring is feasible in Latin–America. General practitioners and specialists from bigger cities seem eager and are self-perceived as well-trained and experienced. Facilities and resources do not seem to be a challenge but training reinforcement and telemedicine promotion is necessary for those physicians less motivated. PLAIN LANGUAGE SUMMARY What is the context? Hypertension is one of the leading worldwide modifiable risk factors for premature death. Strong evidence supports that effective treatment of this condition results in a significant reduction of hard outcomes. Only 20%–30% of hypertensive patients are within the blood pressure targets recommended by guidelines in Latin–America. There is an urgent need to implement innovative strategies to reverse this alarming health situation. What is new? Latin–American physicians were highly predisposed to telemonitoring practice. This high motivation was not influenced by hardware or software availability, technological knowledge or experience, by volume of monthly consultations, or by area (private–public) where the care activity is carried out. This high motivation may be supported by the conviction that this practice could be very useful as a complement to face–to–face assistance and a highly effective tool to improve adherence even though respondents considered that just 10% of the patients would prefer telemonitoring over office consultation. What is the impact? Facilities and resources do not seem to be a challenge but training reinforcement and telemedicine promotion is necessary for those physicians less motivated. The general perception is that it is necessary to move forward to resolve legal gaps and financial aspects. Physicians must adapt to changes and develop new communication strategies in a world where the unrestricted access to teleinformation makes patients self-perceived as experts.

Identifying new drugs associated with pulmonary arterial hypertension: A WHO pharmacovigilance database disproportionality analysis.

We used VigiBase, the largest pharmacovigilance database worldwide to generate disproportionality signals through the Bayesian neural network method. All disproportionality signals were further independently reviewed by experts in pulmonary arterial hypertension, pharmacovigilance and vascular pharmacology and their plausibility ranked according to World Health Organization causality categories. We included 2184 idiopathic PAH cases, yielding a total of 93 disproportionality signals. Among them, 25 signals were considered very likely, 15 probable, 28 possible and 25 unlikely. Notably, we identified 4 new protein kinases inhibitors (lapatinib, lorlatinib, ponatinib and ruxolitinib), 1 angiogenesis inhibitor (bevacizumab), and several chemotherapeutics (etoposide, trastuzumab), antimetabolites (cytarabine, fludarabine, fluorouracil, gemcitabine) and immunosuppressants (leflunomide, thalidomide, ciclosporin). Such signals represent plausible adverse drug reactions considering the knowledge of iatrogenic PAH, the drugs' biological and pharmacological activity and the characteristics of the reported case. Although confirmatory studies need to be performed, the signals identified may help clinicians envisage an iatrogenic aetiology when faced with a patient who develops PAH.

Jeremiah Stamler, MD (1919-2022).

Jeremiah Stamler, MD (1919-2022).

WASOG statement on the diagnosis and management of sarcoidosis-associated pulmonary hypertension.

Sarcoidosis-associated pulmonary hypertension (SAPH) is an important complication of advanced sarcoidosis. Over the past few years, there have been several studies dealing with screening, diagnosis and treatment of SAPH. This includes the results of two large SAPH-specific registries. A task force was established by the World Association of Sarcoidosis and Other Granulomatous disease (WASOG) to summarise the current level of knowledge in the area and provide guidance for the management of patients. A group of sarcoidosis and pulmonary hypertension experts participated in this task force. The committee developed a consensus regarding initial screening including who should undergo more specific testing with echocardiogram. Based on the results, the committee agreed upon who should undergo right-heart catheterisation and how to interpret the results. The committee felt there was no specific phenotype of a SAPH patient in whom pulmonary hypertension-specific therapy could be definitively recommended. They recommended that treatment decisions be made jointly with a sarcoidosis and pulmonary hypertension expert. The committee recognised that there were significant defects in the current knowledge regarding SAPH, but felt the statement would be useful in directing future studies.

A DOUBLE HIT: PULMONARY ARTERIAL HYPERTENSION, BMPR2 MUTATION, AND EXPOSURE TO PRESCRIPTION AMPHETAMINES

TOPIC: Pulmonary Vascular Disease TYPE: Fellow Case Reports INTRODUCTION: Pulmonary arterial hypertension (PAH) management during pregnancy is challenging. We present a case of PAH diagnosed during 3rd trimester of pregnancy, in a patient with familial history of PAH and exposure to prescription-amphetamines. CASE PRESENTATION: 30-year-old primigravid female at 30 weeks of gestation was referred to our Pulmonary Hypertension program for evaluation of rapidly progressive dyspnea, lightheadedness and echocardiogram revealing increased pulmonary pressures. She had a history of Attention-deficit/hyperactivity disorder, treated with dextroamphetamine/amphetamine (Adderall®) and lisdexamfetamine (Vyvanse®) for several years. Her mother had died of pulmonary hypertension at the age of 30. She had functional class III symptoms. An echo showed an estimated right ventricular systolic pressure of 69mm Hg, with right ventricular dilation and dysfunction, as well as interventricular septal flattening. A right heart catheterization (RHC) showed a mPAP of 34 mmHg, PAWP 10 mmHg, cardiac output 3.96 L/min, cardiac index of 2.08 L/min/m2 and PVR of 6.1 WU. She was admitted for expedited work-up and treatment of pulmonary hypertension. Investigational studies were negative for alternative etiologies of pulmonary hypertension, there was no evidence of chronic thromboembolic disease. She was started on a rapid titration with intravenous treprostinil. Once at a dose of 40 ng/kg/min, a repeated RHC showed mPAP of 28 mmHg, PAWP 6 mmHg, cardiac output 5.8 L/min, cardiac index of 3.1 L/min/m2 and PVR of 5.1 WU. A multidisciplinary discussion with high-risk OB, cardiac anesthesia, neonatology and our Pulmonary Hypertension program recommended for C-section under epidural anesthesia with VA-ECMO on stand-by, which was performed at 32 weeks of gestation. Her post-op course was uneventful and she was discharged home on triple therapy with sildenafil, ambrisentan and intravenous treprostinil. She was found to have the BMPR2 mutation. At follow-up, she is functional class II, six-minute walk distance is 530 meters and BNP values are 17 ?g/mL. DISCUSSION: Studies report 75% prevalence of BMPR2 mutations in cases of hereditary PAH, with an autosomal dominant mode of inheritance and incomplete penetrance. It is hypothesized that a "two-hit” phenomenon with environmental influencers like drugs, toxins or infection known to cause pulmonary hypertension may have a role in providing the "second hit” leading to development of the disease. We wonder if the exposure to prescription-amphetamines could have been a second hit, on top of her genetic background. PAH in pregnant females poses a very high risk of maternal and fetal mortality. Aggressive counseling focusing of avoiding pregnancy and early termination should be instituted in all patients. In cases where pregnancy is continued, care at centers with expertise in pulmonary hypertension and ECMO/transplant capability is recommended. CONCLUSIONS: . REFERENCE #1: Geraci MW, Bull TM, Tuder RM. Genomics of pulmonary arterial hypertension: implications for therapy. Heart failure clinics. 2010 Jan 1;6(1):101-14. DISCLOSURES: No relevant relationships by Roberto Bernardo, source=Web Response No relevant relationships by HUZAIFA JALIAWALA, source=Web Response No relevant relationships by Katherine Summers, source=Web Response

Safety and efficacy of balloon pulmonary angioplasty in a Portuguese pulmonary hypertension expert center

Balloon pulmonary angioplasty (BPA) is an alternative therapy in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or residual/recurrent pulmonary hypertension (PH) after surgery. The aim of this study was to assess the short-term efficacy and safety of a BPA program.This prospective single-center study included all BPA sessions performed in CTEPH patients between 2017 and 2019. Clinical assessment including WHO functional class, plasma biomarkers, 6-min walk test (6MWT) and right heart catheterization was performed at baseline and six months after the last BPA session.A total of 57 BPA sessions were performed in 11 CTEPH patients (64% with inoperable disease, 82% under pulmonar vasodilator therapy). Nine patients completed both the BPA program and a minimum six-month follow-up period. There were significant improvements in WHO functional class (p=0.004) and 6MWT (mean increase of 42 m; p=0.050) and a trend for significant hemodynamic improvement: 25% decrease in mean pulmonary artery pressure (mPAP) (p=0.082) and 42% decrease in pulmonary vascular resistance (PVR) (p=0.056). In the group of patients with severely impaired hemodynamics (three patients with mPAP >40 mmHg), the reduction was significant: 51% in mPAP (p=0.013) and 67% in PVR (p=0.050). Prostacyclin analogs and long-term oxygen therapy were withdrawn in all patients. Minor complications were recorded in 25% of patients. There were no major complications or deaths.A BPA strategy on top of pulmonary vasodilator therapy further improves symptoms, exercise capacity and hemodynamics with an acceptable risk-benefit ratio in patients with inoperable CTEPH or residual/recurrent PH after surgery.