Hypertension Clinic Research Articles

Multiple Renal Infarctions in Spontaneous Double Renal Artery Dissection: A Case Report

Background: As spontaneous renal artery dissection (SRAD) is a rare cause of abdominal pain, bilateral dissection is an extremely rare event. Only approximately two hundred cases of SRAD have been reported in the literature. The diagnosis is often delayed due to the rarity of the disease and non-specific clinical presentations such as flank pain, hypertension, fever, nausea, vomiting, and hematuria, which can be often misdiagnosed as a genito-urinary infection or gastrointestinal or bowel disease. Before 1980, the diagnosis of SRAD was mostly confirmed via autopsy or, rarely, via angiography. At present, the diagnosis is made using advanced imaging approaches, including computed tomography angiography (CTA) and magnetic resonance angiography (MRA), with a higher number of incidentally diagnosed SRADs. Methods: we performed laboratory tests and radiological examinations (computed abdominal tomography and multiplanar reconstruction) that revealed multiple infarctions and ischemic areas with hypoperfusion in the upper middle third of the left kidney and in a large part of middle and lower areas of the right kidney; the left renal artery exhibited increased intimal thickening and arteritis. Results: The multiplanar reconstruction revealed bilateral renal artery dissection and multiple arterial infarctions disseminated throughout both kidneys. After a clinical follow-up and hypertension retargeting, the patient was discharged with dual antiplatelet therapy and ACE inhibitor drugs. No lipid-lowering therapy was needed. Conclusions: Spontaneous renal artery dissection (SRAD) is a rare clinical event that typically presents with acute low-back or flank pain, hypertension, fever, hematuria, and acute renal failure. The condition could be misdiagnosed or receive a delayed diagnosis due to its relative rarity and non-specific presentation. The gold standard is enhanced computed tomography (CT) scans, and if the diagnosis is positive, vascular multiplanar reconstruction is generally suggested, as it can display lesions more clearly. Over 300 cases have been reported since the first characterization of SRAD; however, to date, a consensus has not been reached on the most appropriate treatment. Conservative therapy, open surgery, and intravascular intervention have been reported as treatments for SRAD.

Left Atrial Size and Strain in Hypertensive Children Compared to Age-, Sex-, and Race/Ethnicity-Matched Controls.

Left atrial (LA) volume and peak longitudinal strain (LA strain) are indicators of left ventricular (LV) diastolic function in adults, but little is known about LA volume and strain in pediatric patients with hypertension (HTN). We evaluated LA volume and strain in pediatric cases with HTN compared to age-, sex-, and race/ethnicity-matched controls. This was a retrospective matched case-control study of patients who presented to the HTN clinic at CHOP from 12/2011 to 9/2018. Coarctation of the aorta, cardiomyopathy or heart transplantation cases were excluded. HTN was defined by an abnormal ambulatory blood pressure result. LA volume was measured by biplane area-length method and indexed to body surface area (BSA). LA strain and strain rate were measured using TOMTEC® software. Left ventricular mass index (LVMI) was measured by M-mode and the 5/6 area-length method indexed to height2.7. LV global longitudinal strain (LV GLS) was measured during the echocardiographic examination on the GE ultrasound machine for cases and offline using TOMTEC® software for controls. Measurements were compared using Chi-square, McNemar, or Wilcoxon signed rank tests. We included 47 cases and 47 controls. There was no difference in LA volume z-scores (-1.9 vs. -0.9, p = 0.068), LA strain (37.8% vs. 38.0%, p = 0.735) or LA strain rate (1.4 vs. 1.5, p = 0.852) in cases compared to controls. LVMI by M-mode and 5/6 area-length method was higher in cases compared to controls (40.0 vs. 33.7g/m2.7, p < 0.001 and 29.9 vs 24.4g/m2.7, p = < 0.001, respectively). LV GLS was decreased (less negative) in cases compared to controls. In summary there was no difference in LA volume or LA strain in cases compared to controls. In cases, LVMI was significantly elevated and LV GLS was significantly decreased, which may be the first response to HTN, prior to affecting LA size.

Screening for severe coronary stenosis in patients with apparently normal electrocardiograms based on deep learning

BackgroundPatients with severe coronary arterystenosis may present with apparently normal electrocardiograms (ECGs), making it difficult to detect adverse health conditions during routine screenings or physical examinations. Consequently, these patients might miss the optimal window for treatment.MethodsWe aimed to develop an effective model to distinguish severe coronary stenosis from no or mild coronary stenosis in patients with apparently normal ECGs. A total of 392 patients, including 138 with severe stenosis, were selected for the study. Deep learning (DL) models were trained from scratch and using pre-trained parameters via transfer learning. These models were evaluated based on ECG data alone and in combination with clinical information, including age, sex, hypertension, diabetes, dyslipidemia and smoking status.ResultsWe found that DL models trained from scratch using ECG data alone achieved a specificity of 74.6% but exhibited low sensitivity (54.5%), comparable to the performance of logistic regression using clinical data. Adding clinical information to the ECG DL model trained from scratch improved sensitivity (90.9%) but reduced specificity (42.3%). The best performance was achieved by combining clinical information with the ECG transfer learning model, resulting in an area under the receiver operating characteristic curve (AUC) of 0.847, with 84.8% sensitivity and 70.4% specificity.ConclusionsThe findings demonstrate the effectiveness of DL models in identifying severe coronary stenosis in patients with apparently normal ECGs and validate an efficient approach utilizing existing ECG models. By employing transfer learning techniques, we can extract “deep features” that summarize the inherent information of ECGs with relatively low computational expense.

Systemic alpha-1 adrenergic receptor inhibition reduces sperm damage in adult and aging spontaneously hypertensive rats

Decreased sperm quality has been reported in men with different clinical conditions, including aging and hypertension. In the male reproductive tract, it has been suggested that the α1-adrenergic receptor influences fertility and spermatogenesis, and important functions are also attributed to the renin–angiotensin axis, such as regulation of steroidogenesis, spermatogenesis, and sperm function. Previously, our group demonstrated impaired testicular vasomotion via α1-adrenergic receptor activation and increased hypoxia-related proteins in the testes of spontaneously hypertensive rats (SHRs) compared to Wistar normotensive rats. In this study, we aimed to investigate the effect of hypertension and inhibition of systemic α1-adrenergic receptor or angiotensin II AT1 receptor on sperm quality, sperm functional characteristics, and testicular microcirculation in rats from three different ages: young (8–10-week-old), adult (20–24-week-old) and older adult (60–66-week-old). We observed higher blood pressure in SHRs of all ages compared to age-matched Wistar rats. Lower blood pressure was observed either in prazosin or losartan-treated adult or aged SHRs. Additionally, lower sperm concentration, impaired motility and higher acrosome damage were demonstrated in SHRs. Prazosin treatment alleviated the effects of hypertension on sperm concentration and motility but not acrosome damage. Higher vasomotion was noticed in testicular blood vessels of adult and aged SHRs compared to Wistar rats. Thus, impaired sperm quality was observed in SHRs of different ages and was improved by sub-chronically blocking the α1-adrenergic receptor.

Abstract 4138494: Remote Blood Pressure Monitoring and Intervention as a better and cost-effective method of Hypertension control compared to Usual care: A Systematic Review

Introduction/Background: Hypertension is a leading cause of morbidity and mortality. Despite treatment recommendations and encouragement of lifestyle changes, the actual rate of blood pressure control is still not at par. Remote intervention methods have been shown to achieve better rates of blood pressure control utilising lesser resources and lower healthcare costs. We conducted a systematic review by qualitatively evaluating the potential impact of remote monitoring and interventions compared to usual care in controlling Hypertension. Research Question: Are remote monitoring techniques and interventions better than usual in-person blood pressure checks for hypertension control? Methods: We did a comprehensive literature search of Pubmed/MEDLINE, Google scholar, Cochrane central Library, PLOS ONE, ScienceDirect and Clinicaltrials.gov to identify eligible randomised control trials and clinical trials published between July 2013 and May 2025. A Risk of Bias assessment was conducted using Cochrane Risk of Bias tools such as ROB-2 for randomised control trials and ROBINS-1 for cohort studies. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Of the 5,185 records analysed, 10 randomised control trials, 1 cohort study and 1 implementation study satisfied our inclusion criteria. Compared to usual care, remote monitoring methods showed significant difference in systolic blood pressure control at 6-12 months in 9 out of 12 studies, while 3 studies did not show any significant difference. Quality of life, physical health, mental health and drug compliance have also shown a significant positive difference in patients. Remote self monitoring interventions were found to be more cost-effective than usual care. They also reduced the load of patients seeking appointments for hypertension control thereby improving the quality of patient care. Conclusion: The management of clinical hypertension is a challenging entity. Conventional methods of regular in-office blood pressure checks are both tedious and resource consuming. Using remote monitoring methods have shown to significantly improve blood pressure control compared to routine methods. It also eliminates white-coat hypertension during follow-up blood pressure checks which leads to more appropriate interventions. Remote monitoring and intervention for hypertension control is time-effective, cost-effective and improves quality of life.

Evaluation of the Design of Hemodialysis Patient Monitoring System at Lestari Kidney and Hypertension Clinic Semarang

Introduction: Patients diagnosed with kidney disease are very difficult to accept and are not ready to undergo haemodialysis treatment. Objective: Effectiveness is needed to make patients with chronic kidney disease more obedient to treatment and to ask about kidney treatment and important health information for kidney failure patients. Method: The aim of this research is to evaluate the design of a patient's haemodialysis monitoring system in the Gingival Clinic and the Pressure of Current Lester, by conducting research based on methods and qualitative descriptive types of research. Result: Research has shown that Clinical Kidney and Concurrent Lestari Hypertension require a haemodialysis patient monitoring system to facilitate healthcare in patient monitoring and facilitate physicians in decision making.

Multidisciplinary models of primary health care for patients with chronic non-communicable diseases

Introduction. Chronic non-communicable diseases (CNCD) requires a variety of strategies from different perspectives and at different levels, including individual and country-specific. Comprehensive patient-oriented and proactive approaches play an important role in the provision of multidisciplinary teams of medical care to patients with established CNCD. The purpose of this study is to present the Moscow experience in managing multidisciplinary teams for the treatment of CND patients, using the example of arterial hypertension in the framework of a pilot project in the outpatient clinics of the Troitsk and Novomoskovsky administrative districts (TiNAO; were attached to the territory of Moscow in 2012). Materials and methods. The study was conducted in two stages: at the first, a literature review was carried out, at the second, the stages of launching a pilot project on the management of multidisciplinary teams for the treatment patients with CNCD, using the example of arterial hypertension in the outpatient clinic of TinAO, were developed and discussed. Results. The research analyzes approaches to the use of multidisciplinary teams in the world. Based on the analyzed current regulatory documents, adjustments were made to the foreign model for its possible adaptation to Moscow polyclinics, focusing on proactive dispensary dynamic monitoring. Research limitations. The results of the conducted research are based on operational data from Moscow and can be applied only to the formation of management decisions in Moscow. Conclusion. According to the results of the pilot project testing, an increase in the level of coverage of the attached population with medical care, accessibility of narrow specialists and provision of equal opportunities for obtaining medical care for Muscovites was noted.

Adherence to antihypertensive medications in Omani patients: a comparison of drug biochemical analysis and the Morisky Medication Adherence Scale.

Medication nonadherence is a major risk factor for suboptimal or failed hypertension pharmacologic therapy. To determine the nonadherence rate to antihypertensive medications using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the self-reported Morisky Medication Adherence Scale (MMAS). This study used a prospective cross-sectional cohort design. Patients with hypertension aged ≥18 years and prescribed at least one antihypertensive medication were recruited from an outpatient hypertensive clinic at a tertiary healthcare institution in Oman. Adherence was assessed using LC-MS/MS urine analysis and the MMAS. In total, 162 patients completed the MMAS questionnaire and provided urine samples for LC-MS/MS analysis. The overall mean age of the cohort was 55 ± 13 years, and 57% of the patients were men. The mean systolic and diastolic blood pressures were 146 ± 18 mmHg and 79 ± 10 mmHg, respectively. Using the MMAS method, 65% of the patients reported nonadherence. However, LC-MS/MS analysis revealed that only 27% of the patients were nonadherent. The adherent group by LC-MS/MS had significantly lower systolic (P = 0.026) and diastolic blood pressures (P < 0.001) than the nonadherent group, whereas no differences were observed using the MMAS method. There was weak or no agreement between the MMAS and LC-MS/MS results (P = 0.142). Almost one-fourth of our patients with hypertension were nonadherent to their medications. There was a weak concordance between the MMAS and LC-MS/MS methods in detecting medication nonadherence. Further research into noninvasive convenient adherence scales or methods and their correlations with LC-MS/MS analysis is warranted.

HEART RATE VARIABILITY IN OFFSPRING OF NORMOTENSIVE AND HYPERTENSIVE PARENTS: A COMPARATIVE STUDY

Objective: This study aims to evaluate the differences in heart rate variability (HRV), a biomarker of autonomic nervous system, between offspring of normotensive and hypertensive parents to understand the genetic predisposition of autonomic dysfunction. Methods: This study was a cross-sectional observational study.Two groups of healthy adults, offspring of parents with hypertension (n = 50) and offspring of parents with normal blood pressure (n = 50). Short-term HRV was measured using 5-minute electrocardiogram (ECG). HRV indices such as time and frequency domainwere measured. Data were compared by using independent t-tests, with p &lt; 0.05 being considered as statistically significant. Results:The offspring of parents with hypertension showed significantly lower HRV, with SDNN (30.5 ± 8.2 ms) compared to offspring of parents with normal blood pressure (45.2 ± 7.1 ms, p &lt; 0.001). RMSSD also was significantly lower in offspring of hypertensive group. Low-frequency (LF) power was higher in offspring of parents with hypertension,while high-frequency (HF) power was significantly reduced in them compared to the normotensive group. The LF:HF ratio was higher in offspring of parents with hypertension (2.80 ± 0.85) compared to the normotensive group (1.40 ± 0.60, p &lt; 0.001), indicating sympathovagal imbalance. Conclusion: Offspring of parents with hypertension hadlower HRV, suggesting autonomic dysfunction even in the absence of clinical hypertension. These findings emphasize the potential role of genetic predisposition in the early onset of autonomic dysregulation Further studies are required to understand mechanisms contributing to these differences in HRV.

Evaluating an integrated clinical pharmacy service model in an ambulatory cardiac clinic- a single centre study

Abstract Background Evidence suggests that multidisciplinary cardiology clinics improve patient outcomes. Currently, there is limited data on the type of pharmacist-led interventions occurring in cardiac ambulatory clinics in the Australian setting. Purpose The primary aim of this pilot audit is to examine the frequency and type of pharmacist-led interventions in the ambulatory clinics of this specialist hospital. The secondary aim is to assess factors associated with hospital readmissions within 30 days of Pharmacists' reviews. Methods A retrospective pilot audit was conducted for patients who attended an integrated multidisciplinary Heart Failure (HF) and Hypertension (HTN) clinic from April 2023 to February 2024. Patients’ demographics, Charlson comorbidity index (CCI), and the number and types of pharmacist interventions and readmission data 30 days post clinic review were recorded. Descriptive statistics were used to evaluate patient characteristics and logistic regression for hospital readmissions. Results A total of 398 patients were reviewed by pharmacists, with 300 (75%) from the HF clinics and 98 (25%) from the HTN clinics. Patients’ median age was 63± 14.8 years and median CCI was 4± 3.7. Pharmacists documented medication histories for all patients (100%) and provided 355 recommendations, of which 213 (60%) were actioned by the cardiologist. Pharmacists had a face-to-face consultation and provided education and counselling to 175 (44%) patients. The most common types of interventions were related to guideline-directed prescribing and deprescribing (68, 39%), followed by up-titration of current therapies (61, 35%). Pharmacists also provided education on medication adherence and lifestyle modifications (28, 16%) as well as optimizing medications related to other comorbidities (18, 10%). A total of 8 patients (2%) were re-admitted l within 30 days of clinic review from either heart failure exacerbation or hypertensive crisis. Patients who had a face-to-face consultation and education with a pharmacist were less likely to be readmitted within 30 days (P=0.048). However, none of the other predictors tested for readmission such as age (P= 0.572), gender (0.296), history of non-compliance (0.834), CCI (0.984) or a diagnosis of HF or HTN (0.473) were predictors for readmission within 30 days of clinic review. Conclusion Pharmacists play an integral role in the cardiac ambulatory setting by providing expert medication advice and patient education to optimize patients’ outcomes. This study demonstrates that the activities performed by pharmacists working in Australian cardiac clinics are consistent with other international ambulatory clinics. The study also identified opportunities to develop a similar service for other ambulatory clinics at this hospital such as lipid and atrial fibrillation clinics. Additionally, further research is required to assess long term benefit of pharmacist led interventions on cardiac patients.

Prolonged dual antiplatelet therapy in an extended Phase 3 Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Prolonged dual antiplatelet therapy (P-DAPT) is recommended in selected patients beyond 12 months after myocardial infarction (MI). Several risk scores have been developed to estimate the ischemic and bleeding risk and individualize the decision-making process. Purpose We aim to analyse the factors, including ischemic and bleeding scores, associated with P-DAPT prescription in MI patients submitted to a Cardiac Rehabilitation Program (CRP). Methods Patients with ST-segment elevation MI (STEMI) or occlusion MI (OMI) who were submitted to our CRP underwent Phase 2 CRP and were prospectively included. Patients were followed in an extended Phase 3 CRP, and a follow-up visit was scheduled 12 months after hospital discharge. Baseline and follow-up clinical characteristics and treatment after the 12-months visit were registered, specifically P-DAPT. Ischemic (DAPT score) and bleeding (PRECISE-DAPT and CRUSADE scores) risk scores were retrospectively computed. Predictors of P-DAPT were studied by univariate analysis and multivariable binary logistic regression. The model was tested by area under the curve (AUC) analysis in receiver operating characteristic curves. A p&amp;lt;0.05 was considered statistically significant. Results The cohort comprised 78 patients (mean age 61±11 years, 84.6% male). Anterior and inferior STEMI were the most common presentations (43.6% and 47.4%, respectively). The most prevalent cardiovascular risks factors were hypercholesterolemia (85.9%), hypertension (53.8%), smoking habit (46.2%) and diabetes mellitus (23.1%). P-DAPT was prescribed in 39 (50%) patients beyond 12 months after MI, primarily combining aspirin 100mg o.d. and ticagrelor 60mg b.i.d. (n=33, 84.6%). On multivariate analysis, variables associated with P-DAPT prescription were hypertension (HR 4.92 [1.37-17.68], p=0.02), diabetes mellitus (HR 5.13 [1.09-24.09], p=0.04), multivessel disease (HR 5.54 [1.55-19.79], p=0.008), and stent diameter &amp;lt;3mm (HR 5.46 [1.25-23.78], p=0.02). The predictive power of the model was excellent (AUC 0.88 [0.8-0.96], p&amp;lt;0.001). Ischemic (DAPT score) and bleeding (PRECISE-DAPT and CRUSADE) risk scores were not associated with P-DAPT neither in continuous form nor by using their standard cutoffs (≥2, &amp;lt;25 and &amp;gt;40 points, respectively). Conclusions In a real-life cohort of MI patients undergoing extended Phase 3 Cardiac Rehabilitation, P-DAPT was prescribed in half of the population. Clinical (hypertension and diabetes mellitus) and angiographic (multivessel disease and stent diameter &amp;lt;3mm) variables straightforwardly predict the likelihood of receiving P-DAPT, unlike ischemic and bleeding risk scores. The clinical consequences of this management should be further explored.Prolonged DAPT in Cardiac Rehabilitation

Automated quantification of cerebral microbleeds in susceptibility-weighted MRI: association with vascular risk factors, white matter hyperintensity burden, and cognitive function.

To train and validate a deep learning (DL)-based segmentation model for cerebral microbleeds (CMB) on susceptibility-weighted MRI; and to find associations between CMB, cognitive impairment, and vascular risk factors. Participants in this single-institution retrospective study underwent brain MRI to evaluate cognitive impairment between January-September 2023. For training the DL model, the nnU-Net framework was used without modifications. The DL model's performance was evaluated on independent internal and external validation datasets. Linear regression analysis was used to find associations between log-transformed CMB numbers, cognitive function (mini-mental status examination [MMSE]), white matter hyperintensity (WMH) burden, and clinical vascular risk factors (age, sex, hypertension, diabetes, lipid profiles, and body mass index). Training of the DL model (n = 287) resulted in a robust segmentation performance with an average dice score of 0.73 (95% CI, 0.67-0.79) in an internal validation set, (n = 67) and modest performance in an external validation set (dice score = 0.46, 95% CI, 0.33-0.59, n = 68). In a temporally independent clinical dataset (n = 448), older age, hypertension, and WMH burden were significantly associated with CMB numbers in all distributions (total, lobar, deep, and cerebellar; all P <.01). MMSE was significantly associated with hyperlipidemia (β = 1.88, 95% CI, 0.96-2.81, P <.001), WMH burden (β = -0.17 per 1% WMH burden, 95% CI, -0.27-0.08, P <.001), and total CMB number (β = -0.01 per 1 CMB, 95% CI, -0.02-0.001, P = .04) after adjusting for age and sex. The DL model showed a robust segmentation performance for CMB. In all distributions, CMB had significant positive associations with WMH burden. Increased WMH burden and CMB numbers were associated with decreased cognitive function. CMB = cerebral microbleed; DL = deep learning, DSC = dice similarity coefficient; MMSE = mini-mental status examination; SVD = small vessel disease; SWI = susceptibility-weighted image; WMH = white matter hyperintensity.

8356 Total Hypophysectomy in Cushing’s Disease: Results from a Terciary Center

Abstract Disclosure: M.V. Lopes: None. M.D. Severino: None. J. Rocha: None. C.R. Peixe: None. M.I. Alexandre: None. A. Gomes: None. M.J. Bugalho: None. Introduction: Transsphenoidal surgery (TSS) is the first line treatment for Cushing’s disease (CD), leading to remission in 70-80% of cases. Though selective adenomectomy is the preferred approach, total hypophysectomy may be needed. Objective: To describe 3 CD patients in which total hypophysectomy was performed. Clinical cases 1. A 58-year-old man with a history of type 2 diabetes (T2D) and obesity, was referred to the Endocrinology Clinic due to abdominal purple striae and facial plethora. Laboratory tests suggested ACTH dependent hypercortisolism, with normal serum ACTH, high 24h urinary cortisol and no cortisol suppression in the overnight 1mg dexamethasone suppression test (DST). The CRH test was suggestive of CD but no adenoma was found on pituitary MRI. Inferior petrosal sinus sampling (IPSS) was compatible with CD with right-sided lateralization. Right hypophysectomy was performed but no CD remission was achieved, so the patient underwent total hypophysectomy. Corticotroph hyperplasia was identified in histology. After 9 months of follow-up, he mantains CD remission. 2.A 37-year-old woman was diagnosed with ACTH dependent hypercortisolism after referral to the Endocrinology Clinic for alopecia, amenorrhea, hypertension and hirsutism. Laboratory tests showed severe hypokalemia, high plasma ACTH and 24h urinary cortisol and the MRI showed a right-sided macroadenoma. Nonetheless, considering the clinical severity, an IPSS was performed and definitely excluded an ectopic Cushing’s syndrome (CS) thus confirming the diagnosis of CD with right-sided lateralization. The patient underwent selective TSS, however, for lack of CD remission, total hypophysectomy was performed. Histology revealed an adenocorticotrophic adenoma. Yet, a year later, she maintains persistence of CD, although less severe, and is under treatment with metyrapone. 3.A 58-year-old woman with a history of T2D and class 3 obesity, was evaluated in our Endocrinology Clinic due to obesity. Her physical examination suggested CS, so this hypothesis was investigated. Laboratory tests suggested ACTH dependent hypercortisolism, with normal serum ACTH, elevated 24h urinary cortisol and no cortisol suppression in the overnight 1mg DST. The high dose DST was suggestive of CD but the pituitary MRI didn’t show an adenoma. IPSS was compatible with CD but it was not possible to determine lateralization. So, total hypophysectomy was performed. An adenocorticotrophic adenoma was identified in histology. Postoperative CD remission was achieved and persists 3 months later. Conclusions: These 3 cases highlight the challenge of treating CD and suggest that in certain cases total hypophysectomy may be the treatment of choice to cure or at least improve CD. Although it is associated with more complications than selective TSS, our patients had no complications, only developed panhypopituitarism and diabetes insipidus. Presentation: 6/1/2024

7236 Long Term Extension of Osilodrostat Therapy in Canadian Patients with Cushing’s Disease Benefiting from the LINC 3 and LINC 4 Studies

Abstract Disclosure: L.M. Martel: Other; Self; LMD receives partial fellowship salary support though educational grants from Recordati Rare Disease Canada Inc and Pfizer Canada. G. Houde: Other; Self; GH served as a consultant for Novartis. C. Chik: Other; Self; grants and/or consulting fees from Pfizer, Ipsen, Novartis and Novo Nordisk Canada. S.A. Imran: Other; Self; consulting fees from Pfizer, Recordati and Novartis. E. Paron: Other; Self; employees of Recordati Rare Disease Canada Inc. F. Lebel: Other; Self; employees of Recordati Rare Disease Canada Inc. A. Lacroix: Other; Self; reports grants and personal consulting fees from Novartis, Recordati and Pfizer. Introduction: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided rapid, sustained cortisol normalization in Cushing’s disease (CD) patients in two Phase III trials (LINC 3, NCT02180217; LINC 4, NCT02697734); persistent biochemical and clinical improvement of CD were reported after 72 and 96 weeks of therapy, respectively (10.1530/EJE-22-0317; 10.3389/fendo.2023.1236465). After study completion and continued clinical benefit with osilodrostat, patients could transition in a roll-over study (CLCI699C2X01B , NCT03606408). As osilodrostat is now approved for therapy of CS in Europe and CD in USA, but not in Canada, seven Canadian patients who had benefited from osilodrostat were transitioned to an investigator initiated study ((ISS-CA-2023, NCT06131580). Objective: To analyze the course of therapy with osilodrostat which allowed long-term biochemical and clinical control of CD since initiation of LINC 3 and LINC 4 core studies for up to 105 months. Methods: Retrospective review of clinical, biochemical and imaging data were collected through chart review of 11patients enrolled in four Canadian centers in LINC 3 and 4 in LINC 4 parent studies. Seven patients remained in the roll-over study until termination and initiation of the Canadian study on October 24 2023. Data from initiation of therapy until October 24 2023 were analyzed. Results: Of the eleven enrolled patients, four discontinued treatment due to muscle cramps, repeat transsphenoidal surgery (TSS) for corticotroph adenoma progression in 2 cases, and hyperandrogenism and opting for bilateral adrenalectomy in one case. Seven cases (5 LINC 3 and 2 LINC 4) pursued therapy in the extension study: 2 men and 5 women, mean age 46 y.o. (range 28-72). All but one had previous TSS, one Gamma Knife and 4 received previous medical therapy. The median 24 hour urinary free cortisol (UFC) before starting osilodrostat was 334 nnmol/d (2.4 x ULN; range 133-414). The median treatment duration was 82 months (range 67-105) and median time to normalize UFC was 36 days. The median maximal dose required to normalize UFC was 10 mg/day (4-60); dose was frequently reduced because of symptoms of relative cortisol withdrawal or adrenal insufficiency (n: 5) to 6.5 mg/day (range: 1 mg every 6 days to 30 mg/d) currently. Last median UFC was 60 nmol/d (range 22-154; 6/7 in normal range &amp;lt; 138nmol/d). Tumor growth occurred in 1 patient (2mm). All patients presented partial to complete improvement of CD features, whereas one patient developed moderate clinical hyperandrogenism, hypertension and borderline prolongation of QTc that normalized after a dose reduction. Conclusions: Osilodrostat can provide sustained biochemical and clinical control of hypercortisolism in patients with CD for up to 9 years; however drug efficacy and dose requirement varies greatly between patients and must be adjusted carefully and regularly during course of therapy. Presentation: 6/3/2024

8401 Genetic Characterization of a Case of Primary Aldosteronism in an 11-Year-Old Girl carrying a Germline VUS of CACNA1H and a Somatic Mutation of CTNNB1

Abstract Disclosure: S. Parisien-La Salle: None. G. Van Vliet: None. G. Corbeil: None. M. Labrecque: None. M. Tétreault: None. I. Bourdeau: None. Introduction: Primary aldosteronism is a frequent cause of secondary hypertension in adults but is rare in children. We report the case and genetic studies of an 11 yo girl presenting with primary aldosteronism at puberty. Case presentation: An 11-year-old female patient was referred to the pediatric endocrinology clinic for hypertension (166/118). Her past medical history and family history were unremarkable. She reported polyuria, polydipsia and occasional headaches and abdominal pain. Her Tanner stage indicated that puberty was initiated (P2M2). An abdominal CT revealed a 9x10x11cm right adrenal mass with calcifications and a necrotic zone. On [1]8F-FDG PET/CT, the mass had an uptake of 2.9 SUVmax. Laboratory results revealed hypokalemia (K: 2.6 mmol/L [N: 3.5-4.5]) and elevated aldosterone (1712.8 pmol/L [N: 110-1330]) with suppressed renin (0.2 ng/ml/h [N: &amp;lt;5.3]). Her urinary aldosterone level was elevated (114 nmol/day [N: &amp;lt;67]). The rest of the biochemical adrenal panel was normal. Patient underwent a right adrenalectomy by laparotomy. The pathology report showed an adrenal tumor without capsular or vascular invasion. The only malignancy criterion was an area of necrosis and the ki-67% proliferation index was &amp;lt; 1%. Genetic investigations: After informed consent, the patient underwent germline analysis for the chimeric gene CYP11B2/CYP11B1 (Ruhr University Bochum, Germany) and a multigene panel including KCNJ5, CACNA1D, CACNA1H and CLCN2 genes (Fulgent, CA), which were both negative except for a variant of unknown significance (VUS) that was identified in CACNA1H (c.3868G&amp;gt;A, p.Val1290Ile) with a minor allele frequency of 3.291E-5 (GnomAD). Tumor DNA was extracted after adrenalectomy from fresh frozen tissues. Somatic genetic analysis of GNAS, CTNNB1, KCNJ5, ATP1A1, ATP2B3 and CACNA1D was performed using direct Sanger Sequencing (Genome Quebec Innovation Centre) and revealed a heterozygous missence pathogenic variant in the CTNNB1 gene (c.121 A&amp;gt;G p.Thr41Ala). This mutation was absent in leukocyte DNA of the patient. Immunohistochemistry of the adrenal tumor disclosed strong cytoplasmic β-catenin staining in most tumor cells (monoclonal anti-β-catenin antibody; BD Transduction Laboratories). RNA-sequencing of patient tumor RNA was performed (Research Center CHU Québec) and compared to human adrenal total RNA (Clontech, Mountain View, CA). Pathway enrichment analysis showed activation of the Wnt signaling pathway. No variant was identified in GNAQ or GNA11 genes. However, GNRHR was upregulated compared to the control sample with a log2 fold change of 3.96 (p=0.000074). Conclusion: We present a rare pediatric case of an aldosterone producing adenoma harbouring a somatic β-catenin pathogenic variant with upregulation of GNRHR. The implication of the germline CACNA1H VUS still needs to be clarified. Presentation: 6/3/2024

Identifying pseudo-resistant hypertension and optimizing diuretic therapy for confirmed resistant cases in primary care.

Approximately 10% of individuals with hypertension are expected to have resistant hypertension (RH). Many have pseudo-resistant hypertension (p-RH) due to a variety of factors. To date, the prevalence of p-RH and optimal diuretic therapy in primary care have not been studied. A retrospective chart review was conducted, including patients referred to the hypertension clinic at the Centre for Family Medicine (CFFM) Family Health Team in Kitchener, ON, from January 2010 to September 2020. Individuals ≥18 years old referred to clinic by their family physician or other health care provider with 2 consecutive blood pressure (BP) readings of ≥140/90 mmHg despite using ≥3 antihypertensive agents were included. Fifty-one patients taking ≥3 antihypertensive agents were referred during the study timeframe. Forty-one patients had ≥2 consecutive BP readings of ≥140/90 and were classified as having presumed RH. Of these, 24 patients (59%) had p-RH after BP was measured systematically in the hypertension clinic. Of the 17 with RH, 5 (29%) were prescribed optimal diuretic therapy upon referral. Most common clinic interventions included initiating or adjusting the dose of a diuretic (47%), adding a different antihypertensive agent (27%) or discontinuing an antihypertensive agent due to side effects (24%). To our knowledge, this is the first time that the prevalence of p-RH and optimal diuretic therapy have been studied in primary care. p-RH was common and diuretic therapy was underused in RH. This study suggests that p-RH is prevalent and diuretic therapy underused in primary care. Systematic BP measurement and optimization of diuretic therapy should be prioritized prior to specialist referral.

Impact of a Disease-Focused Electronic Health Record Dashboard on Clinical Staff Efficiency in Previsit Patient Review in an Ambulatory Pulmonary Hypertension Care Clinic.

We aimed to improve the operational efficiency of clinical staff, including physicians and allied health professionals, in the previsit review of patients by implementing a disease-focused dashboard within the electronic health record system. The dashboard was tailored to the unique requirements of the clinic and patient population. A prospective quality improvement study was conducted at an accredited pulmonary hypertension (PH) clinic within a large academic center, staffed by two full time physicians and two allied health professionals. Physicians' review time before and after implementation of the PH dashboard was measured using activity log data derived from an EHR database. The review time for clinic staff was measured through direct observation, with review method-either conventional or newly implemented dashboard-randomly assigned. Over the study period, the median number of patients reviewed by physicians per day increased slightly from 5.50 (interquartile range [IQR]: 1.35) before to 5.95 (IQR: 0.85) after the implementation of the PH dashboard (p = 0.535). The median review time for the physicians decreased with the use of the dashboard, from 7.0 minutes (IQR: 1.55) to 4.95 minutes (IQR: 1.35; p < 0.001). Based on the observed timing of 70 patient encounters among allied clinical staff, no significant difference was found for experienced members (4.65 minutes [IQR: 2.02] vs. 4.43 minutes [IQR: 0.69], p = 0.752), while inexperienced staff saw a significant reduction in review time after familiarization with the dashboard (5.06 minutes [IQR: 1.51] vs. 4.12 minutes [IQR: 1.99], p = 0.034). Subjective feedback highlighted the need for further optimization of the dashboard to align with the workflow of allied health staff to achieve similar efficiency benefits. A disease-focused dashboard significantly reduced physician previsit review time while that for clinic staff remained unchanged. Validation studies are necessary with our patient populations to explore further qualitative impacts on patient care efficiency and long-term benefits on workflow.

Correction to “An audit of the initial 12 months of a multi‐disciplinary pulmonary hypertension clinic in South Western Sydney (Campbelltown Hospital)”

Correction to “An audit of the initial 12 months of a multi‐disciplinary pulmonary hypertension clinic in South Western Sydney (Campbelltown Hospital)”

In vivo safety assessment of a polyherbal formulation (Stress WIN) proposed for clinical hypertension management

Herbal treatments are nowadays considered dietary supplements and nutraceuticals for health maintenance and alternative/complementary therapy. A large range of herbal medications worldwide can easily be accessible in the local market. The polyherbal formulation (Stress WIN) containing Ashwagandha (Withania somnifera L. Dunal), Pushkarmoola (Inula racemosa Hook. F.), and Jatamansi (Nardostachys jatamansi (D. Don) DC.) root has been used empirically in the management of hypertension. However, toxicity data for the StressWIN is not available yet. The present study aims to evaluate the StressWIN’s safety profile by 28 days of repeated dose oral toxicity in Wistar rats. Rats received different doses (500 mg/kg/day, 1000 mg/kg/day, and 2000 mg/kg/day) of StressWIN, for 28 days. The study was conducted in compliance with the OECD guideline 423. No significant differences were observed in hematological and biochemical parameters as compared to the control group (p > 0.05). Histopathological studies revealed no significant alterations in the macroscopic and microscopic architecture of the liver, kidney, heart, and spleen of the StressWIN treated groups in comparison to the control group (p > 0.05). Findings from the present study suggest that StressWIN supplementation has not shown any side effects in terms of sub-acute toxicity in both male and female rats. These findings indicated no observed adverse effect level (NOAEL) of StressWIN was higher than 2000 mg/kg/day.

Patient-Related Factors Influencing Drug Non-Compliance among Hypertensive Patients in Selected State Hospitals in Lagos, Nigeria

Drug non-compliance for some time has remained a major health-related issue among chronic diseases, especially among hypertensive patients. Drug non-compliance in middle and low-income countries including Nigeria is attributed to many factors but aggravated by economic recession. There have not been sufficient studies, particularly theory-based, which explored drug non-compliance among hypertensive patients at the secondary health facilities. Understanding major factors that could influence drug non-compliance is a key step in controlling hypertension. Thus, this study aims to explore patient-related factors influencing drug non-compliance among hypertensive patients in selected state hospitals in Lagos State, Nigeria. The study adopted quantitative and qualitative research designs using descriptive surveys and Key Informant Interviews (KII) with a sample size of 349 participants among patients with hypertension in cardiac outpatient clinics of the selected general hospitals. Responses were also collected from purposively selected healthcare providers through oral interviews and their responses were analyzed qualitatively. Survey data were analyzed using Statistical Package for Social Science (SPSS) version 25.0. The study revealed that both old and young patients are ignorant of the disease thus, they tend to forget their drug prescriptions. The study further discovered that poverty and inability to procure their drugs regularly often make them turn to unorthodox medicine, and these were responsible for drug non-compliance. The study recommended that government and healthcare-providing institutions should intensify efforts to educate patients on drug compliance so as to prevent complications resulting from drug non-compliance.