Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: The EnligHTN I trial

Aims: Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN™ multi-electrode system. Methods and results: We conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN™ system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by −28/10, −27/10 and −26/10 mmHg, respectively (P < 0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2). Conclusion: Renal sympathetic denervation, using the EnligHTN™ multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN™ system delivers a promising therapy for the treatment of drug-resistant hypertension.Stephen G. Worthley, Costas P. Tsioufis, Matthew I. Worthley, Ajay Sinhal, Derek P. Chew, Ian T. Meredith, Yuvi Malaiapan, and Vasilios Papademetrio

Proceedings from the 2nd European Clinical Consensus Conference for device-based therapies for hypertension: state of the art and considerations for the future.

The interest in RDN for hypertension has fluctuated recently, with a flurry of initial enthusiasm followed by sudden loss of interest by researchers and device manufacturers, with an almost as sudden resurgence in clinical trials activity and device innovation more recently. There is widespread consensus that this therapeutic strategy can be effective, at least for some of the technologies available. Major uncertainties remain as to the clinical role of RDN, and whether any of the emerging technologies such as AV-anastomosis formation, carotid body ablation, carotid bulb expansion, or baroreflex stimulation will have a future as effective treatment options in patients with hypertension. In our first consensus report in 2015, the European Expert Group pointed to the major unmet need of standardization of measurements, trial design and procedural performance.6 With the large number of different technologies currently in the pipeline, this need has even increased. Only through high-quality, collaborative research and openness to new methods for recruitment, patient selection, and assessment of outcomes will it be possible to establish incontrovertibly whether device therapies for hypertension are effective and what are preferred patient populations. Once the proof of concept is established, further studies with a design relevant to clinical reality will be needed to establish the place of new devices in the treatment armoury. The clinical and research community has a large responsibility to prove or disprove the value of new therapies, in order to ensure that antihypertensive devices provide future patients with the greatest benefit and the smallest risk. copy; The Author 2017

Asymptomatic Chronic Large Pericardial Effusions: To Drain or to Observe?

Pericardial effusions, especially large ones, have traditionally been regarded with concern by clinicians due to the sometimes unpredictable development of life-threatening cardiac tamponade. In the European Society of Cardiology Guidelines on pericardial diseases, the simplified algorithm for pericardial effusion triage and management recommends pericardial drainage in cases of cardiac tamponade and/or suspicion of bacterial or neoplastic etiology. In the presence of acute pericarditis, empiric anti-inflammatory treatment should be given, while when a specific indication known to be associated with pericardial effusion is found, then treatment of the underlying cause is indicated. Notably, the most challenging subgroup of patients includes those with large, asymptomatic, C-reactive-protein-negative, idiopathic effusions. In the latter subjects, pericardial drainage is proposed in cases of chronic effusions (lasting more than three months). However, this recommendation is based on scant data stemming from small-sized non-randomized studies. Nevertheless, recent evidence in a larger cohort of patients pointed out that a watchful waiting strategy is a safe option in terms of complication-free survival. This review summarizes the contemporary evidence on this challenging topic and provides recommendations for tailoring individual patient treatments

The correlates of urinary albumin to creatinine ratio (ACR) in a high risk Australian Aboriginal community

Background: Albuminuria marks renal disease and cardiovascular risk. It was estimated to contribute 75% of the risk of all-cause natural death in one Aboriginal group. The urine albumin/creatinine ratio (ACR) is commonly used as an index of albuminuria. This study aims to examine the associations between demographic factors, anthropometric index, blood pressure, lipid-protein measurements and other biomarkers and albuminuria in a cross-sectional study in a high-risk Australian Aboriginal population. The models will be evaluated for albuminuria at or above the microalbuminuria threshold, and at or above the "overt albuminuria" threshold with the potential to distinguish associations they have in common and those that differ

Diagnostic and therapeutic approach to acute blood pressure elevations: results of an international survey among excellence centres of the European society of hypertension.

Acute blood pressure (BP) elevations are common in emergency settings and are traditionally classified into hypertensive urgencies (HU) and hypertensive emergencies (HE). Malignant hypertension (MHT) represents a severe form of HE characterised by small vessel damage. Although international guidelines provide clear definitions and treatment strategies, real-world data have shown persistent fragmentation and heterogeneity in the diagnosis and management of these patients. A web-based, anonymous survey promoted by the European Society of Hypertension (ESH) was distributed among physicians from 18 European and 4 non-European countries. The questionnaire assessed definitions, diagnostic work-up, BP measurement practices, and therapeutic strategies for HU, HE, and MHT. Sixty-four participants in 56 centres completed the survey. HU was correctly defined as a severe BP elevation without acute clinically symptomatic hypertension-mediated organ damage (A-HMOD) by 45.3% of respondents. Small cuffs were available to 79.7% and extra-large cuffs to 70.3% of respondents.. Intravenous antihypertensive therapy was used for HE by 88.7% of participants, while 20.6% also used intravenous drugs for HU. Parenteral clonidine and sublingual nifedipine were prescribed by 29.7% and 26.6% of respondents, respectively. Definitions and therapeutic approaches for MHT varied substantially, with 62.9% adopting a recently proposed definition involving at least three target organ damages in patients with BP &gt;200/120 mmHg. This international survey highlights considerable variability in the definition, diagnostic work-up, and therapeutic management of acute BP elevations, emphasising the need for harmonised protocols and further education

Outcomes of acute pericarditis with an inflammatory phenotype

Background: Patients with pericarditis may show elevation of C-reactive protein (CRP) and pericardial effusion at presentation. There are limited data on the prognostic implications of this inflammatory phenotype. Objectives: Aim of the present study is to evaluate the outcome of the inflammatory phenotype in a cohort of patients with acute pericarditis. Methods: Observational cohort study of consecutive adult patients with acute pericarditis in 4 referral centers for pericarditis (Athens, Milan, Turin, Udine). Results: Our cohort included 918 patients with acute pericarditis (median age of 56, IQR 28 years, 55.6 % females). The etiology of pericarditis was respectively idiopathic in 82.1 %, post-cardiac injury syndrome in 9.3 %, and systemic inflammatory disease in 4.9 % of cases. CRP elevation was detected at presentation in 778 cases (84.7 %), an inflammatory phenotype (CRP elevation and pericardial effusion) was found in 557 patients (60.7 %). Baseline medical therapy included a NSAID in 74.9 %, colchicine 70.9 %, and corticosteroids 25.1 % of cases. After a mean follow-up of 22.5 months, patients with an inflammatory phenotype had a higher recurrence rate at 18 months (respectively 46.0 % vs. 31.0 %; p < 0.0001), and a shorter recurrence-free survival (Log-rank p = 0.0001). In multivariable analysis the inflammatory phenotype presentation was independently associated with an increased risk of recurrences (OR 2.005, 95 % CI 1.454 to 2.765; p < 0.0001). Conclusions: The inflammatory phenotype of presentation of acute pericarditis is associated with an increased risk of recurrences, highlighting the importance of timely individualized therapy and close follow-up for these patients

Targeting the sympathetic nervous system with the selective imidazoline receptor agonist moxonidine for the management of hypertension: an international position statement

Hypertension is often linked with metabolic risk factors that share common pathophysiological pathways. Despite wide-spread availability of multiple drug classes, optimal blood pressure (BP) control remains challenging. Increased central sympathetic outflow is frequently neglected as a critical regulator of both circulatory and metabolic pathways and often remains unopposed therapeutically. Selective imidazoline receptor agonists (SIRAs) effectively reduce BP with a favorable side effect profile compared with older centrally acting antihypertensive drugs. Hard outcome data in hypertension, such as prevention of stroke, heart and kidney diseases, are not available with SIRAs. However, in direct comparisons, SIRAs were as effective as angiotensin-converting enzyme inhibitors, β-blockers, calcium channel blockers, and diuretics in lowering BP. Other beneficial effects on metabolic parameters in hypertensive patients with concomitant overweight and obesity have been documented with SIRAs. Here we review the existing evidence on the safety and efficacy of moxonidine, a widely available SIRA, compared with common antihypertensive agents and provide a consensus position statement based on inputs from 12 experts from Europe and Australia on SIRAs in hypertension management

Exercise tolerance and quality of life in patients with known or suspected coronary artery disease

Background: Coronary artery disease (CAD) is known to impact on patients’ physical and mental health. The relationship between performance on treadmill exercise tolerance test (ETT) and health-related quality of life (HRQL)has never been specifically investigated in the setting of CAD. Methods: Consecutive patients undergoing an ETT with the Bruce protocol during a diagnostic workup for CAD (n = 1,631, age 55 ± 12&nbsp;years) were evaluated. Exercise-related indices were recorded. Detailed information on cardiovascular risk factors and past medical history were obtained. HRQLwas assessed with the use of the validated 36-Item Short Form Survey (SF-36) questionnaire. Results: Increasing age and the presence of cardiovascular risk factors and comorbidities correlated with lower scores on the physical and mental health component of SF-36(all P &lt; 0.05). Subjects with arrhythmias during exercise and slow recovery of systolic blood pressure had lower scores on the physical health indices or the Social Role Functioning component (P &lt; 0.05). Achieved target heart rate and good exercise tolerance were independently associated with better scores of the physical and mental health domains of SF-36 and overall HRQLscores (β = 0.05 for target HR and PCS-36, β = 1.86 and β = 1.66 per increasing stage of exercise tolerance and PCS-36 and MCS-36, respectively, P &lt; 0.001 for all associations). Ischemic ECG changes were associated with worse scores on Physical Functioning (β = − 3.2, P = 0.02) and Bodily Pain (β = − 4.55, P = 0.026). Conclusion: ETT parameters are associated with HRQL indices in patients evaluated for possible CAD. Physical conditioning may increase patient well-being and could serve as a complementary target in conjunction with cardiovascular drug therapy