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.

Mediterranean diet and blood pressure reduction in adults with and without hypertension: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: It is unclear whether the Mediterranean diet (MedDiet) has a favorable effect on blood pressure (BP) levels because among randomized controlled trials (RCTs) investigating the MedDiet-mediated BP reduction significant methodological and clinical differences are observed. The purpose of this study was to comprehensively assess the MedDiet BP-effect compared to the usual diet or another dietary intervention (e.g. low-fat diet) in adults with and without hypertension, accounting for methodological and clinical confounders. METHODS: We systematically searched Medline and the Cochrane Collaboration Library databases and identified 35 RCTs (13,943 participants). Random-effects model was used to calculate the mean attained systolic BP (SBP) and diastolic BP (DBP) differences during follow-up. Subgroup and meta-regression analyses were also conducted. RESULTS: Compared to the usual diet and all other active intervention diets the MedDiet reduced SBP and DBP (difference in means: -1.5 mm Hg; 95% CI: -2.8, -0.1; P = 0.035, and -0.9 mm Hg; 95% CI: -1.5, -0.3; P = 0.002, respectively). Compared only to the usual diet the MedDiet reduced SBP and DBP, while compared to all other active intervention diets or only to the low-fat diet the MedDiet did not reduce SBP and DBP. The MedDiet reduced DBP levels to a higher extent in trials with mean baseline SBP ≥130 mm Hg, while both SBP and DBP were reduced more in trials with a mean follow-up period ≥16 weeks. The quality of evidence was rated as moderate for both outcomes according to the grading of recommendations, assessment, development and evaluation (GRADE) approach. CONCLUSIONS: The adoption of the MedDiet was accompanied by a relatively small, but yet significant BP reduction, while higher baseline SBP levels and longer follow-up duration enhanced the BP-lowering effect of the intervention. This meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42020167308. REGISTRY NUMBER: CRD42020167308.

Dietary Approaches to Stop Hypertension (DASH) Diet and Blood Pressure Reduction in Adults with and without Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The Dietary Approaches to Stop Hypertension (DASH) diet is recognized as an effective dietary intervention to reduce blood pressure (BP). However, among randomized controlled trials (RCTs) investigating the DASH diet-mediated BP reduction, there are significant methodological and clinical differences. The purpose of this study was to comprehensively assess the DASH diet effect on BP in adults with and without hypertension, accounting for underlying methodological and clinical confounders. We systematically searched Medline and the Cochrane Collaboration Library databases and identified 30 RCTs (n = 5545 participants) that investigated the BP effects of the DASH diet compared with a control diet in hypertensive and nonhypertensive adults. Both random-effects and fixed-effect models were used to calculate the mean attained systolic BP (SBP) and diastolic BP (DBP) differences during follow-up. Subgroup and meta-regression analyses were also conducted. Compared with a control diet, the DASH diet reduced both SBP and DBP (difference in means: -3.2 mm Hg; 95% CI: -4.2, -2.3 mm Hg; P < 0.001, and -2.5 mm Hg; 95% CI: -3.5, -1.5 mm Hg; P < 0.001, respectively). Hypertension status did not modify the effect on BP reduction. The DASH diet compared with a control diet reduced SBP levels to a higher extent in trials with sodium intake >2400 mg/d than in trials with sodium intake ≤2400 mg/d, whereas both SBP and DBP were reduced more in trials with mean age <50 y than in trials of older participants. The quality of evidence was rated as moderate for both outcomes according to the Grading of Recommendations, Assessment, Development, and Evaluation approach. The adoption of the DASH diet was accompanied by significant BP reduction in adults with and without hypertension, although higher daily sodium intake and younger age enhanced the BP-lowering effect of the intervention. This meta-analysis was registered at www.crd.york.ac.uk/prospero as CRD42019128120.

Serial changes in vessel walls of renal arteries after catheter-based renal artery denervation: insights from volumetric computed tomography analysis.

AIM: Radiofrequency ablation of peri-arterial renal autonomic nerves has been studied as a potential therapeutic option for resistant hypertension. While recent clinical trials have reported its efficacy, there is paucity of data addressing the effects of the procedure on renal arteries, such as changes in vessel and lumen areas. Herein, the effect of atheroma burden on renal arteries after renal denervation was assessed using computed tomography (CT) imaging. MATERIALS AND METHODS: Serial renal artery CT imaging was conducted in 38 patients from the EnligHTN™ I study, a prospective, multicenter study evaluating the efficacy of the EnligHTN multi-electrode radiofrequency ablation catheter in resistant hypertensive subjects. Cross-sectional images of renal arteries at 1 mm intervals were acquired using commercially available software (3mensio Structural Heart version 5.1). Vessel and lumen areas were manually traced in each image. Vessel wall volume (VWV) and percent vessel wall volume (P-VWV) were calculated. The measurements within the ablation (first 30 mm segments) and the non-ablation (subsequent 30 mm segment after the first bifurcation of renal arteries) zones were compared. RESULTS: On serial evaluation, greater increase in P-VWV and VWV was observed in the ablation zone (change in P-VWV, 6.7%±5.1% vs 3.6%±2.8%, P=0.001; change in VWV, 106.3±87.4 vs 23.0±18.2 mm3, P=0.001). Receiver-operating characteristic analysis demonstrated baseline P-VWV in the ablation zone >37.1% as an optimal cutoff value to predict its substantial progression after the procedure (area under the curve=0.88, sensitivity 89.8%, specificity 79.1%). CONCLUSION: Change in vessel wall was greater within the segments receiving renal artery denervation. Baseline VWV predicted its substantial increase after the procedure. These observations suggest that atheroma burden within the renal arteries is a potential contributing factor to vascular changes after renal sympathetic denervation.

Clinical Diagnosis and Management of Resistant Hypertension.

Resistant hypertension (RHT) is variably defined as insufficient blood pressure (BP) response to multiple drug treatment. Prevalence of RHT has been thoroughly studied in the recent years, ranging from about 5 to 30 % in various cohorts. Initial management of patients with apparent RHT requires identification of true treatment resistance by out-of-office BP measurements, assessment of adherence and screening for treatable causes of uncontrolled BP. Endorsement of lifestyle modifications and maximisation of the doses of a suitable regimen, preferably with the further addition of an aldosterone antagonist, are the mainstay of treatment. An invasive approach to RHT, mainly represented by renal nerve ablation, should be kept for persistently severe cases managed in a specialised hypertension centre.

Catheter-based renal denervation for resistant hypertension: Twenty-four month results of the EnligHTN I first-in-human study using a multi-electrode ablation system.

BACKGROUND: Long term safety and efficacy data of multi-electrode ablation system for renal denervation (RDN) in patients with drug resistant hypertension (dRHT) are limited. METHODS AND RESULTS: We studied 46 patients (age: 60 ± 10 years, 4.7 ± 1.0 antihypertensive drugs) with drug resistant hypertension (dRHT). Reduction in office BP at 24 months from baseline was -29/-13 mmHg, while the reduction in 24-hour ambulatory BP and in home BP at 24 months were -13/-7 mmHg and -11/-6 mmHg respectively (p<0.05 for all). A correlation analysis revealed that baseline office and ambulatory BP were related to the extent of office and ambulatory BP drop. Apart from higher body mass index (33.3 ± 4.7 vs 29.5 ± 6.2 kg/m(2), p<0.05), there were no differences in patients that were RDN responders defined as ≥10 mmHg decrease (74%, n=34) compared to non-responders. Stepwise logistic regression analysis revealed no prognosticators of RDN response (p=NS for all). At 24 months there were no new serious device or procedure related adverse events. CONCLUSIONS: The EnligHTN I study shows that the multi-electrode ablation system provides a safe method of RDN in dRHT accompanied by a clinically relevant and sustained BP reduction.

Exaggerated carotid sinus massage responses are related to severe coronary artery disease in patients being evaluated for chest pain.

BACKGROUND: Previous studies have reported that carotid sinus massage responses are associated with advancing age and carotid or coronary artery disease. HYPOTHESIS: This study was undertaken to investigate the potential role of carotid sinus hypersensitivity as a marker for the presence of coronary artery disease, and especially left main stem disease, in patients who were referred for evaluation of chest pain. METHODS: Toward this end, carotid sinus stimulation with simultaneous recordings of the electrocardiogram and aortic pressure was performed before coronary arteriography in 150 selected consecutive patients (mean age 59.4+/-9 years) who were referred for evaluation of chest pain. RESULTS: Coronary artery disease was present in 118 patients (78.7%); of these, 35 had single-vessel disease, 35 had double-vessel disease, 33 had triple-vessel disease, and 15 had left main stem with or without such vessel disease. Carotid sinus hypersensitivity was found in 40 patients (26.6%). The incidence of hypersensitivity in patients with single-, double-, or triple-vessel disease and left main stem disease was 8.5, 14.2, 57.5, and 73.3%, respectively. Stepwise multiple logistic regression analysis revealed that left main stem disease was significantly and independently related to the presence of carotid sinus hypersensitivity (p < 0.05). In addition, the presence of hypersensitivity had 73.3% sensitivity, 86.2% specificity, and 96.3% negative predictive value for the presence of left main stem disease. CONCLUSION: In patients being evaluated for suspected ischemic heart disease, carotid sinus massage responses are related to severe coronary disease. The absence of hypersensitivity may reflect absence of left main stem disease.

Catheter-based renal denervation for resistant hypertension: 12-month results of the EnligHTN I first-in-human study using a multielectrode ablation system.

Renal denervation has emerged as a novel approach for the treatment of patients with drug-resistant hypertension. To date, only limited data have been published using multielectrode radiofrequency ablation systems. In this article, we present the 12-month data of EnligHTN I, a first-in-human study using a multielectrode ablation catheter. EnligHTN I enrolled 46 patients (average age, 60±10 years; on average 4.7±1.0 medications) with drug-resistant hypertension. Eligible patients were on ≥3 antihypertensive medications and had a systolic blood pressure (BP) ≥160 mm Hg (≥150 mm Hg for diabetics). Bilateral renal artery ablation was performed using a percutaneous femoral approach and standardized techniques. The average baseline office BP was 176/96 mm Hg, average 24-hour ambulatory BP was 150/83 mm Hg, and average home BP was 158/90 mm Hg. The average reductions (mm Hg) at 1, 3, 6, and 12 months were as follows: office: -28/-10, -27/-10, -26/-10, and -27/-11 mm Hg (P<0.001 for all); 24-hour ambulatory: -10/-5, -10/-5, -10/-6 (P<0.001 for all), and -7/-4 for 12 months (P<0.0094). Reductions in home measurements (based on 2-week average) were -9/-4, -8/-5,-10/-7, and -11/-6 mm Hg (P<0.001 at 12 months). At 12 months, there were no signals of worsening renal function and no new serious or life-threatening adverse events. One patient with baseline nonocclusive renal artery stenosis progressed to 75% diameter stenosis, requiring renal artery stenting. The 12-month data continue to demonstrate safety and efficacy of the EnligHTN ablation system in patients with drug-resistant hypertension. Home BP measurements parallel measurements obtained with 24-hour ambulatory monitoring.

Impact of waist circumference on cardiac phenotype in hypertensives according to gender.

Our aim was to assess the differential effect of waist circumference on left-ventricular (LV) structural and functional alterations, in hypertensive males and females. One thousand seven hundred and eighty nine consecutive, nondiabetic, essential hypertensives (aged 55.8 +/- 13.5 years, 966 females), included in the 3H Study, an ongoing registry of hypertension-related-target-organ damage, were classified to obese and nonobese groups according to Adult Treatment Panel III criteria. All participants underwent complete echocardiographic study including LV diastolic function evaluation by means of conventional and tissue Doppler imaging (TDI) methods, averaging early and late diastolic mitral annular peak velocities (Em, Am, Em/Am) from four separate sites of measurement. Hypertensive obese women compared with nonobese exhibited significantly greater LV mass index and prevalence of LV hypertrophy (by 5.5 g/m(2), P = 0.003, and 8.8%, P = 0.005, respectively), while such differences were not present among men. Obese women compared to nonobese ones were accompanied by lower transmitral E/A (by 0.08, P < 0.001), TDI-derived Em/Am (by 0.12, P < 0.001), and higher E/Em ratio (by 0.8, P = 0.016). In contrast, hypertensive obese men compared to nonobese ones exhibited lower E and Em (by 0.04 m/s and 0.6 cm/s, both P < 0.05). A significant interaction between sex and abdominal obesity was observed only regarding TDI-derived Am and Em/Am. Furthermore, waist circumference was a predictor of E/A (beta = -0.097, P = 0.002) and Em/Am (beta = -0.116, P = 0.001), independently of body size, in females but not in males. The adverse effect of abdominal obesity on LV alterations is more pronounced among female hypertensives, suggesting that routine measurement of waist circumference provides additional information on cardiac phenotype especially in women.