Therapy-resistant Hypertension Research Articles

Effects of baroreflex activation therapy on cardiac function and morphology.

Arterial hypertension (aHTN) plays a fundamental role in the pathogenesis and prognosis of heart failure with preserved ejection fraction (HFpEF). The risk of heart failure increases with therapy-resistant arterial hypertension (trHTN), defined as inadequate blood pressure (BP) control ≥140/90mmHg despite taking ≥3 antihypertensive medications including a diuretic. This study investigates the effects of the BP lowering baroreflex activation therapy (BAT) on cardiac function and morphology in patients with trHTN with and without HFpEF. Sixty-four consecutive patients who had been diagnosed with trHTN and received BAT implantation between 2012 and 2016 were prospectively observed. Office BP, electrocardiographic and echocardiographic data were collected before and after BAT implantation. Mean patients' age was 59.1years, 46.9% were male, and mean body mass index (BMI) was 33.2kg/m2. The prevalence of diabetes mellitus was 38.8%, atrial fibrillation was 12.2%, and chronic kidney disease (CKD) stage ≥3 was 40.8%. Twenty-eight patients had trHTN with HFpEF, and 21 patients had trHTN without HFpEF. Patients with HFpEF were significantly older (64.7 vs. 51.6years, P<0.0001), had a lower BMI (30.0 vs. 37.2kg/m2, P<0.0001), and suffered more often from CKD-stage ≥3 (64 vs. 20%, P=0.0032). After BAT implantation, mean office BP dropped in patients with and without HFpEF (from 169±5/86±4 to 143±4/77±3mmHg [P=0.0019 for systolic BP and 0.0403 for diastolic BP] and from 170±5/95±4 to 149±6/88±5mmHg [P=0.0019 for systolic BP and 0.0763 for diastolic BP]), while a significant reduction of the intake of calcium-antagonists, α2-agonists and direct vasodilators, as well as a decrease in average dosage of ACE-inhibitors and α2-agonists could be seen. Within the study population, a decrease in heart rate from 74 ± 2 to 67 ± 2 min-1 (P=0.0062) and lengthening of QRS-time from 96±3 to 106±4ms (P=0.0027) and QTc-duration from 422±5 to 432±5ms (P=0.0184) were detectable. The PQ duration was virtually unchanged. In patients without HF, no significant changes of echocardiographic parameters could be seen. In patients with HFpEF, posterior wall diameter decreased significantly from 14.0±0.5 to 12.7±0.3mm (P=0.0125), left ventricular mass (LVM) declined from 278.1±15.8 to 243.9±13.4g (P=0.0203), and e' lateral increased from 8.2±0.4 to 9.0±0.4cm/s (P=0.0471). BAT reduced systolic and diastolic BP and was associated with morphological and functional improvement of HFpEF.

The use of echocardiography compared to electrocardiogram when screening for left ventricular hypertrophy in hypertensive patients: A cross-sectional study.

Left ventricular hypertrophy (LVH) is often used as an indicator to assess hypertension-mediated organ damage (HMOD), alongside hypertensive retinopathy (HR) and nephropathy. Assessment of HMOD is crucial when making decisions about treatment optimization. Despite longstanding debate over its reliability to detect LVH, it is common practice to perform an electrocardiogram (ECG) instead of directly assessing left ventricular mass with echocardiography. In this study, the presence of LVH was evaluated using both ECG and echocardiography among consecutive patients suspected of therapy-resistant hypertension or secondary hypertension in the outpatient clinic of the Department of Internal Medicine at the Diakonessen Hospital, Utrecht, the Netherlands, between July 15, 2017, and July 31, 2020. The primary endpoints were the specificity and sensitivity of ECG as a diagnostic tool for LVH, with echocardiography serving as the reference method. Among the 329 participants, we identified 70 individuals (21.3%) with true LVH based on echocardiography. The ECG displayed a sensitivity of 47.9% and a specificity of 75.3%. Moreover, the area under the receiver operating characteristics curve was 0.604. In conclusion, ECG demonstrates limited value in identifying LVH. Considering the importance of accurately assessing HMOD for treatment optimization of hypertension, the role of ECG as a diagnostic tool for LVH is, therefore, questionable. Instead, we recommend employing standard echocardiography as a more reliable diagnostic.

Efficacy and Safety of Radiofrequency-Based Renal Denervation on Resistant Hypertensive Patients: A Systematic Review and Meta-analysis.

New therapies for resistant hypertension (RH), including renal denervation (RDN), have been studied. Access the safety and effectiveness of radiofrequency-based RDN vs pharmacological treatment for RH. A thorough literature search was conducted across PubMed, EMBASE, and the Cochrane databases, focusing on studies that compared the effects of radiofrequency-based RDN versus pharmacological treatment for RH. Treatment effects for binary and continuous endpoints were pooled and used, respectively, odds-ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) to analyze continuous outcomes. In the 10 included studies, involving 1.182 patients, 682 received radiofrequency-based RDN. The follow-up period ranged from 6 to 84 months. Analysis revealed that the RDN group had a significant reduction in office systolic blood pressure (BP) (MD - 9.5 mmHg; 95% CI - 16.81 to - 2.29; P = 0.01), office diastolic BP (MD - 5.1 mmHg; 95% CI - 8.42 to - 2.80; P < 0.001), 24 h systolic BP (MD - 4.8 mmHg; 95% CI - 7.26 to - 2.42; P < 0.001). For 24 h diastolic BP RDN did not have a significant reduction (MD - 2.3 mmHg; 95% CI - 4.19 to - 0.52; P = 0.012). The heterogeneity between the studies was high, visible in the funnel and Baujat plots. The OR was non-significant for non-serious adverse events, but also clinically significant for hypertensive crises and strokes for the RDN group. While the pharmacological regimen of 3 or more anti-hypertensive, including a diuretic, still be the first-line option for RH treatment, our results support that radiofrequency-based RDN is superior in reducing global BP and is safe.

Clinical Relevance of Rapid FOXF1-Targeted Sequencing in Patients Suspected of Alveolar Capillary Dysplasia With Misalignment of Pulmonary Veins

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal congenital lung disorder that presents shortly after birth with respiratory failure and therapy-resistant pulmonary hypertension. It is associated with heterozygous point mutations and genomic deletions that involve the FOXF1 gene or its upstream regulatory region. Patients are unresponsive to the intensive treatment regimens and suffer unnecessarily because ACDMPV is not always timely recognized and histologic diagnosis is invasive and time consuming. Here, we demonstrate the usefulness of a noninvasive, fast genetic test for FOXF1 variants that we previously developed to rapidly diagnose ACDMPV and reduce the time of hospitalization.

The therapeutic concordance approach reduces adverse drug reactions in patients with resistant hypertension.

Adverse drug reactions (ADRs) remain among the leading causes of therapy-resistant hypertension (TRH) and uncontrolled blood pressure (BP). We have recently reported beneficial results in BP control in patients with TRH adopting an innovative approach, defined as therapeutic concordance, in which trained physicians and pharmacists reach a concordance with patients to make them more involved in the therapeutic decision-making process. The main scope of this study was to investigate whether the therapeutic concordance approach could lead to a reduction in ADR occurrence in TRH patients. The study was performed in a large population of hypertensive subjects of the Campania Salute Network in Italy (ClinicalTrials.gov Identifier: NCT02211365). We enrolled 4,943 patients who were firstly followed-up for 77.64 ± 34.44 months, allowing us to identify 564 subjects with TRH. Then, 282 of these patients agreed to participate in an investigation to test the impact of the therapeutic concordance approach on ADRs. At the end of this investigation, which had a follow-up of 91.91 ± 54.7 months, 213 patients (75.5%) remained uncontrolled while 69 patients (24.5%, p < 0.0001) reached an optimal BP control. Strikingly, during the first follow-up, patients had complained of a total of 194 ADRs, with an occurrence rate of 68.1% and the therapeutic concordance approach significantly reduced ADRs to 72 (25.5%). Our findings indicate that the therapeutic concordance approach significantly reduces ADRs in TRH patients.

New Generation of sGC Stimulators: Discovery of Imidazo[1,2-a]pyridine Carboxamide BAY 1165747 (BAY-747), a Long-Acting Soluble Guanylate Cyclase Stimulator for the Treatment of Resistant Hypertension.

Herein, we describe the identification, chemical optimization, and preclinical characterization of novel soluble guanylate cyclase (sGC) stimulators. Given the very broad therapeutic opportunities for sGC stimulators, new tailored molecules for distinct indications with specific pharmacokinetics, tissue distribution, and physicochemical properties will be required in the future. Here, we report the ultrahigh-throughput (uHTS)-based discovery of a new class of sGC stimulators from an imidazo[1,2-a]pyridine lead series. Through the extensive and staggered optimization of the initial screening hit, liabilities such as potency, metabolic stability, permeation, and solubility could be substantially improved in parallel. These efforts resulted ultimately in the discovery of the new sGC stimulators 22 and 28. It turned out that BAY 1165747 (BAY-747, 28) could be an ideal treatment alternative for patients with hypertension, especially those not responding to standard anti-hypertensive therapy (resistant hypertension). BAY-747 (28) demonstrated sustained hemodynamic effects up to 24 h in phase 1 studies.

PS-B05-4: COMPARATIVE EFFECTS OF RENAL DENERVATION IN DIFFERENT STAGES OF HYPERTENSION ON CARDIAC, RENAL, AND ADIPOSE PATHOLOGY IN DAHL SALT-SENSITIVE RATS

Objective: Renal denervation (RDN) has emerged as a novel therapy for resistant hypertension. In Dahl salt-sensitive (DahlS) rats, RDN does not prevent the development of hypertension but attenuates the progression of hypertension. We have now investigated the comparative effects of RDN in early versus advanced stages of hypertension on cardiac, renal, and adipose tissue pathology in DahlS rats. Design and method: Male DahlS rats fed an 8% NaCl diet after 6 weeks of age were subjected to RDN or sham surgery at 7 (early stage) or 9 (advanced stage) weeks. In the RDN groups, all visible nerves along the vessels were cut and the vessels were painted with a solution of 10% phenol in absolute ethanol. In contrast, in the sham-operated groups, the kidneys were exposed but the vessels were not stripped or coated with phenol. At 12 weeks, left ventricular (LV), renal, and adipose tissue were excised for analysis. Results: Successful RDN was confirmed by determination of renal norepinephrine content in each rat subjected to RDN less than 10% of the mean values of those in the sham-operated groups. Although both stages of RDN modestly attenuated blood pressure elevation, they improved LV diastolic function and fibrosis and attenuated macrophage infiltration and expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) genes in the heart, to a similar extent. In addition, both stages of RDN similarly reduced macrophage infiltration in glomeruli, the glomerulosclerosis index, the tubulointerstitial injury score as well as expression of MCP-1 and TNF-α genes in the kidney. The early stage group showed reductions in both retroperitoneal fat mass and adipocyte cross-sectional area, whereas the advanced stage group did an increase in fat mass without any change in adipocyte size. Conclusions: Both early and advanced stages of RDN mildly attenuated hypertension as well as ameliorated cardiac and renal injury, to a similar extent, in salt-loaded DahlS rats. The anti-hypertensive effect of RDN is thus likely attributable primarily to improved renal pathology. These results also suggest a possible crosstalk among the kidney, cardiovascular system, and adipose tissue via neural mechanisms in salt-sensitive hypertension.

Devices for the treatment of arterial hypertension

Abstract Hypertension is still the cause of many cardiovascular complications and the premature death of a large number of patients despite the use of increasingly effective pharmacological drugs. Most patients with therapy-resistant hypertension show excessive activity of the sympathetic system. In the last two decades, there have been successful attempts at nonpharmacological reduction of this activity. The earliest method for this purpose is the denervation of the renal arteries by using devices specially designed for this purpose. Other methods of lowering blood pressure are the electrical activation of baroreceptors, which increases the tone of the parasympathetic system, and special pacemaker software to lower blood pressure. The paper discusses the studies assessing the effectiveness and safety of these methods, and on the basis of the current research results, predictions are made concerning which patients with arterial hypertension would be the most appropriate for these treatment methods.

Therapeutic concordance improves blood pressure control in patients with resistant hypertension

IntroductionAn empathetic approach may be particularly useful in patients with therapy-resistant hypertension (TRH), defined as the failure to achieve target blood pressure (BP) despite a maximal doses of 3 antihypertensive drugs including a diuretic. However, the effects of therapeutic concordance have not been determined in hypertensive patients. MethodsWe designed a study to explore the impact of therapeutic concordance in patients with TRH, who were included in an intervention arm based on a protocol in which trained personnel periodically verified the pharmacological regimen of these patients. ResultsFrom a cohort of 5331 hypertensive patients followed-up for 77.64 ± 34.44 months, 886 subjects were found to have TRH; of these, 322 had apparent TRH (aTRH: uncontrolled office BP but optimal home BP) and 285 refused to participate in a second follow-up study, yielding a population of 279 patients with true TRH (tTRH). These tTRH patients were followed according to the therapeutic concordance protocol for 91.91 ± 54.7 months, revealing that 210 patients (75.27%) remained with uncontrolled BP (uncontrolled tTRH, Group I) while 69 patients (24.73%) reached an optimal BP control (average BP <140/90 mmHg in at least 50% of follow-up visits, Group II). Strikingly, at the end of the second follow-up, the percentage of patients displaying a decline in kidney function was significantly smaller in Group II than in Group I (8.5% vs 23.4%, p < 0.012). ConclusionsTaken together, our findings indicate for the first time that therapeutic concordance significantly improves the outcome of antihypertensive treatment in a population of patients with TRH.

Efficacy and safety of adrenergic alpha-1 receptor antagonists in older adults: a systematic review and meta-analysis supporting the development of recommendations to reduce potentially inappropriate prescribing

BackgroundAdrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and in the management of therapy-resistant arterial hypertension, two conditions frequently found in older adults. This systematic review aims at presenting a complete overview of evidence over the benefits and risks of alpha-1 antagonist treatment in people ≥ 65 years, and at deriving recommendations for a safe application of alpha-1 antagonists in older adults from the evidence found.MethodsA comprehensive literature search was performed (last update March 25th 2022) including multiple databases (Medline/Pubmed, Embase, the Cochrane Library) and using the PICOS framework to define search terms. The selection of the studies was done by two independent reviewers in a two-step approach, followed by a systematic data extraction. Quality appraisal was performed for each study included using standardised appraisal tools. The studies retrieved and additional literature were used for the development of recommendations, which were rated for strength and quality according to the GRADE methodology.ResultsEighteen studies were included: 3 meta-analyses, 6 randomised controlled trials and 9 observational trials. Doxazosin in the management of arterial hypertension was associated with a higher risk of cardiovascular disease, particularly heart failure, than chlorthalidone. Regarding treatment of LUTS suggestive of BPH, alpha-1 antagonists appeared to be effective in the relief of urinary symptoms and improvement of quality of life. They seemed to be less effective in preventing disease progression. Analyses of the risk profile indicated an increase in vasodilation related adverse events and sexual adverse events for some agents. The risk of falls and fractures as well as the effects of long-term treatment remained unclear. All meta-analyses and 5 out of 6 interventional studies were downgraded in the quality appraisal. 7 out of 9 observational studies were of good quality.ConclusionsIt cannot be recommended to use doxazosin as first-line antihypertensive agent neither in older adults nor in younger patients. In the management of BPH alpha-1 antagonists promise to effectively relieve urinary symptoms with uncertainty regarding their efficacy in preventing long-term progression events.

Is ectopic Cushing's syndrome underdiagnosed in patients with small cell lung cancer?

IntroductionEctopic Cushing’s syndrome (ECS) is an uncommon disorder. Recently, however, a larger proportion of patients with endogenous Cushing’s syndrome (CS) had ECS than has previously been reported.ObjectiveThe aim of this study was to determine whether ECS is an underdiagnosed disorder in patients with small-cell lung cancer (SCLC).Materials and methodsMedical records from consecutive patients diagnosed with SCLC at our hospital between 2013 and 2019 were reviewed (N = 213; mean age 69.5 ± 9 years; range, 36–89 years). The probability of having ECS was evaluated by review of biochemical and clinical features, including presence of recent onset diabetes mellitus, therapy resistant hypertension and/or spontaneous hypokalaemia.ResultsOf 213 identified patients with SCLC, one (0.5%) patient had confirmed ECS, two (1%) patients had probable ECS, and twenty-three (11%) patients had possibly ECS. Patients with SCLC and possibly or probable ECS exhibited a significantly shorter survival than patients only with SCLC (8 vs. 14 months, respectively).ConclusionsOur findings indicate that ECS is underdiagnosed in patients with SCLC. Given the serious consequences of untreated ECS, the low detection rate highlights the need to improve endocrine work-up of patients with SCLC who present with biochemical and clinical features associated with ECS. Prospective studies are needed to establish a reliable assessment of the incidence of ECS and to optimise early detection strategies.

Long-term follow-up of patients undergoing renal sympathetic denervation

ObjectivesRenal denervation (RDN) proved to significantly lower blood pressure (BP) at 2–6 months in patients on and off antihypertensive drugs. Given a lack of longer-term follow-up data, our aim was to assess the safety and efficacy of RDN up to five years taking into account antihypertensive drug regimen changes over time.MethodsIn the present single-center study, patients underwent RDN for (therapy resistant) hypertension. Patients underwent protocolized yearly follow-up out to five years. Data were collected on 24-h ambulatory BP and office BP monitoring, renal function, antihypertensive drug regimen, and safety events, including non-invasive renal artery imaging at 6/12 months. Efficacy analyses were performed using linear mixed-effects models.ResultsSeventy-two patients with mean age 63.3 ± 9.5 (SD) years (51% female) were included. Median follow-up time was 3.5 years and Clark’s Completeness Index was 72%. Baseline ambulatory daytime BP was 146.1/83.7 ± 17.4/12.2 mmHg under a mean number of 4.9 ± 2.7 defined daily doses (DDD). At five years, ambulatory daytime systolic BP as calculated from the mixed model was 120.8 (95% CI 114.2–127.5) mmHg and diastolic BP was 73.3 (95% CI 69.4–77.3) mmHg, implying a reduction of -20.9/-8.3 mmHg as compared to baseline estimates (p < 0.0001). The number of DDDs remained stable over time (p = 0.87). No procedure-related major adverse events resulting in long-term consequences were observed.ConclusionsThe BP-lowering effect of RDN was safely maintained at least five years post-procedure as reflected by a significant decrease in ambulatory daytime BP in the absence of escalating antihypertensive drug therapy over time.Graphical abstract

SST2 Predicts Short Term Therapy Success in Patients with Therapy Resistant Hypertension after Renal Sympathetic Denervation

Background: Renal sympathetic denervation (RSD) has provided promising data in its ability to treat therapy resistant arterial hypertension. The effect of RSD on sST-2, a promising biomarker for risk stratification in cardiovascular diseases, has so far not been systematically studied. Methods: We evaluated serum levels of sST-2 and clinical parameter including left ventricular mass (LVM) in 54 patients with resistant hypertension (RH) undergoing bilateral RSD at baseline as well as at one and/or three months. Results: After RSD, mean office blood pressure showed a significant decrease after one month (p &lt; 0.001). On echocardiography a reduction of LVM was observed at three months (p &lt; 0.01). This was accompanied by a significant decrease of sST-2 levels at three months (sST-2 baseline: 6310.1 ± 3246.0 pg/mL vs. sST-2 three months: 4703.8 ± 1585.9 pg/mL, p = 0.048). Furthermore, baseline sST-2 levels were positively correlated with systolic blood pressure at one month (r = 0.514, p &lt; 0.01) but not three months, indicating a potential predictive value of sST-2 for early intervention success. Conclusion: In patients with RH, RSD is associated with a significant decrease of sST-2 levels after three months, indicating sST-2 to be involved in remodeling processes after RSD. Furthermore, lower sST-2 levels at baseline might be a potential predictor of early intervention success of RSD.

SGC stimulation lowers elevated blood pressure in a new canine model of resistant hypertension

Therapy-resistant hypertension is a serious medical problem, causing end-organ damage, stroke, and heart failure if untreated. Since the standard of care fails in resistant hypertension patients, there is still a substantial unmet medical need for effective therapies. Active stimulation of soluble guanylyl cyclase via novel soluble guanylyl cyclase stimulators might provide an effective treatment option. To test this hypothesis, we established a new experimental dog model and investigated the effects of the soluble guanylyl cyclase-stimulator BAY 41-2272. In beagle dogs, a resistant hypertension phenotype was established by combining unilateral renal wrapping with the occlusion of the renal artery in the contralateral kidney. The most frequently used antihypertensive drugs were administered orally, either alone or in combination, and their acute effect on telemetric measured blood pressure was assessed and compared with that of BAY 41-2272. The chosen disease stimulus led to a moderate and stable increase in blood pressure. Even high doses of standard-of-care antihypertensives only slightly decreased blood pressure. In contrast, the administration of the soluble guanylyl cyclase stimulator BAY 41-2272 as standalone therapy led to a dose-dependent reduction in blood pressure (−14.1 ± 1.8 mmHg). Moreover, BAY 41-2272 could also further decrease blood pressure in addition to a triple combination of standard-of-care antihypertensives (−28.6 ± 13.2 mmHg). BAY 41-2272 was highly efficient as a standalone treatment in resistant hypertension but was also effective in addition to standard-of-care treatment. These data strongly suggest that soluble guanylyl cyclase stimulators might provide an effective pharmacologic therapy for patients with resistant hypertension.

Glypican 1 and syndecan 1 differently regulate noradrenergic hypertension development: Focus on IP3R and calcium

BackgroundVascular dysfunction is a checkpoint to the development of hypertension. Heparan sulfate proteoglycans (HSPG) participate in nitric oxide (NO) and calcium signaling, key regulators of vascular function. The relationship between HSPG-mediated NO and calcium signaling and vascular dysfunction has not been explored. Likewise, the role of HSPG on the control of systemic blood arterial pressure is unknown. Herein, we sought to determine if the HSPG syndecan 1 and glypican 1 control systemic blood pressure and the progression of hypertension. PurposeTo determine the mechanisms whereby glypican 1 and syndecan 1 regulate vascular tone and contribute to the development of noradrenergic hypertension. Experimental approach and key resultsBy assessing systemic arterial blood pressure we observed that syndecan 1 (Sdc1-/-) and glypican 1 (Gpc1-/-) knockout mice show a similar phenotype of decreased systolic blood pressure that is presented in a striking manner in the Gpc1-/- strain. Gpc1-/- mice are also uniquely protected from a norepinephrine hypertensive challenge failing to become hypertensive. This phenotype was associated with impaired calcium-dependent vasoconstriction and altered expression of calcium-sensitive proteins including SERCA and calmodulin. In addition, Gpc1-/- distinctively showed decreased IP3R activity and increased calcium storage in the endoplasmic reticulum. Conclusions and implicationsGlypican 1 is a trigger for the development of noradrenergic hypertension that acts via IP3R- and calcium-dependent signaling pathways. Glypican 1 may be a potential target for the development of new therapies for resistant hypertension or conditions where norepinephrine levels are increased.

Resistant arterial hypertension: the search of new approaches to antihypertensive drug therapy

Improving the effectiveness of drug therapy and reducing the risk of adverse cardiovascular and renal outcomes in patients with resistant hypertension (HTN) remains an unsolved problem of cardiology. The results of the PATHWAY-2, PATHWAY-3 and ReHOT studies have shown the clinical efficacy of spironolactone, amiloride and, to a lesser extent, the antiadrenergic drugs clonidine, bisoprolol and doxazosin in improving blood pressure (BP) control in this patient population. However, the inclusion of spironolactone and other known drugs in antihypertensive therapy does not ensure the achievement of target BP level in a significant proportion of these patients. The review presents the results of clinical studies of new approaches aimed at increasing the effectiveness of drug therapy in resistant HTN including sodium-glucose cotransporter type 2 inhibitors, brain aminopeptidase A inhibitors, and new antagonists of endothelin receptors.

Assessment of a strategy combining ambulatory blood pressure, adherence monitoring and a standardised triple therapy in resistant hypertension

Purpose Poor adherence to drug therapy and inadequate drug regimens are two frequent factors responsible for the poor blood pressure (BP) control observed in patients with apparent resistant hypertension. We evaluated the efficacy of an antihypertensive management strategy combining a standardised therapy with three long acting drugs and electronic monitoring of drug adherence in patients with apparent resistant hypertension. Materials and Methods In this multicentric observational study, adult patients with residual hypertension on 24 h ambulatory BP monitoring (ABMP) despite the use of three or more antihypertensive drugs could be included. Olmesartan/amlodipine (40/10 mg, single pill fixed-dose combination) and chlorthalidone (25 mg) were prescribed for 3 months in two separated electronic pills boxes (EPB). The primary outcome was 24 h ambulatory systolic BP (SBP) control at 3 months, defined as mean SBP <130 mmHg. Results We enrolled 48 patients (36.0% women) of whom 35 had complete EPB data. After 3 months, 52.1% of patients had 24 h SBP <130 mmHg. 24 h SBP decreased by respectively −9.1 ± 15.5 mmHg, −22.8 ± 30.6 mmHg and −27.7 ± 16.6 mmHg from the tertile with the lowest adherence to the tertile with the highest adherence to the single pill combination (p = 0.024). A similar trend was observed with tertiles of adherence to chlorthalidone. Adherence superior to 90% was associated with 24 h systolic and diastolic blood pressure control in multiple logistic regression analysis (odds ratio = 14.1 (95% confidence interval 1.1–173.3, p = 0.039). Conclusions A simplified standardised antihypertensive therapy combined with electronic monitoring of adherence normalises SBP in about half of patients with apparent resistant hypertension. Such combined management strategy enables identifying patients who need complementary investigations and those who rather need a long-term support of their adherence.

HartWacht telemonitoring effectively reduces blood pressure in a real-life setting

Abstract Introduction Telemedicine platforms have the potential to reduce costs and improve outcomes in blood pressure reduction. Although results in the literature are promising, evidence remains limited and few home monitoring programs have successfully been integrated into daily clinical practice. The HartWacht home monitoring program is set-up for remote monitoring and treatment of patients with therapy resistant hypertension (systolic blood pressure&amp;gt;140 mmHg and &amp;gt;1 antihypertensive drugs). HartWacht is fully integrated into clinical care and is reimbursed by the majority of Dutch healthcare insurers. Purpose The purpose of this study is to evaluate the effectiveness of the HartWacht program in blood pressure treatment in a real-life setting, and evaluate the number of interventions necessary to reach normotension. Methods In this single center retrospective cohort study, we included all patients with therapy resistant hypertension that were included in the HartWacht program by their treating physician. At baseline, all patients measure blood pressure twice a day for the duration of one week, after which blood pressure measurements were performed once a week. Two pre-set alarms informed a team of designate nurses if blood pressures exceeded 140/90 mmHg (orange alarm) or 180/110 mmHg (red alarm). After one red or two successive orange alarms, the patient was contacted by telephone for guideline driven lifestyle advice or medication adjustment in consultation with a cardiologist. After every intervention, a blanking period of four weeks was set in which no orange alarms were visible. Results The cohort consisted of 161 patients (mean age 63±9.8 years; 54% male). The median follow up time was 318 days. At baseline, the mean blood pressure was 155/91 mmHg. During follow-up mean blood pressure decreased significantly to 134/83 mmHg (p&amp;lt;0.001 for both systolic and diastolic blood pressure). At follow up, 102 (62%) patients were normotensive. During follow up participants received a mean of 0.46 lifestyle advices and 0.74 medication changes in 1.07 consultations. Conclusion Home monitoring and treatment of patients therapy resistant hypertension with HartWacht resulted in a significant overall reduction of blood pressure, with &amp;gt;60% of patients being normotensive at last follow-up. Normotension in HartWacht patients Funding Acknowledgement Type of funding source: None

Interventional recanalisation of long segment aortic atresia

We report the case of a long-segment aortic atresia as the cause for therapy resistant arterial hypertension in a young adult. Recanalization was achieved interventionally by wire-crossing and stent implantation with subsequent normalization of blood pressure.

Retrospective cohort study to characterise the blood pressure response to spironolactone in patients with apparent therapy-resistant hypertension using electronic medical record data

ObjectiveIdentify blood pressure (BP) response to spironolactone in patients with apparent therapy-resistant hypertension (aTRH) using electronic medical records (EMRs) in order to estimate response in a real-world clinical setting.DesignDeveloped an...