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.

Long term safety and efficacy data of multi-electrode ablation system for renal denervation (RDN) in patients with drug resistant hypertension (dRHT) are limited. 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. 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.

Tsioufis CP ，Papademetriou V ，Dimitriadis KS ，Kasiakogias A ，Tsiachris D ，Worthley MI ，Sinhal AR ，Chew DP ，Meredith IT ，Malaiapan Y ，Thomopoulos C ，Kallikazaros I ，Tousoulis D ，Worthley SG ... -  《-》

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.

Papademetriou V ，Tsioufis CP ，Sinhal A ，Chew DP ，Meredith IT ，Malaiapan Y ，Worthley MI ，Worthley SG ... -  《-》

Impact of multi-electrode renal sympathetic denervation on short-term blood pressure variability in patients with drug-resistant hypertension. Insights from the EnligHTN I study.

Transluminal renal sympathetic denervation (RDN) has been shown to reduce blood pressure (BP) in patients with treatment-resistant hypertension. We assessed the effect of multi-electrode RDN on short-term BP variability indexes in resistant hypertensives. Thirty-one patients with drug-resistant uncontrolled hypertension, participants in the EnligHTN I study, underwent ambulatory BP measurements at baseline and 6months after RDN using the EnligHTN ablation catheter (St. Jude Medical). Twelve resistant hypertensives matched for office BP served as control group. At 6months post-RDN, office BP and 24-hour BP were reduced by 25.6/10.3mmHg and by 10.2/6mmHg (p<0.001 for all cases), respectively. No significant changes were observed 6months post-RDN in standard short-term BP variability indexes including 24-hour systolic and diastolic average real variability. The rates of systolic and diastolic 24-hour BP variation were decreased 6months after RDN, (from 0.40/0.30 to 0.34/0.24, p=0.030/0.006, respectively), especially in the responders group (n=23, 74.2%). No significant differences in BP and BP variability parameters in the control group were detected. ROC analysis revealed an area under the curve for prediction of response to RDN by systolic time rate of 66.8% (95% CI: 46.7% to 87%; p=0.16) and by diastolic time rate of 76.1% (95% CI: 58.2% to 93.9%; p=0.030). Although standard BP variability indexes remained unchanged, the rate of systolic and diastolic BP variation was significantly decreased 6months after RDN in patients with drug-resistant hypertension. These novel indexes might also be useful as predictors of response.

Tsioufis C ，Papademetriou V ，Tsiachris D ，Kasiakogias A ，Kordalis A ，Thomopoulos C ，Dimitriadis K ，Tousoulis D ，Stefanadis C ，Parati G ，Worthley S ... -  《-》

Safety and performance of the second generation EnligHTN™ Renal Denervation System in patients with drug-resistant, uncontrolled hypertension.

Catheter-based renal denervation for the treatment of drug-resistant hypertension has been intensively investigated in recent years. To date, only limited data have been published using multi-electrode radiofrequency ablation systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and performance of the second generation EnligHTN™ Renal Denervation System. This first-in-human, prospective, multi-center, non-randomized study included 39 patients (62% male, mean age 63 years, and mean baseline office blood pressure 174/93 mmHg) with drug-resistant hypertension. The primary safety and performance objectives were to characterize, from baseline to 6 months post procedure, the rate of serious procedural and device related adverse events, as adjudicated by an independent Clinical Events Committee, and the reduction of office systolic blood pressure. Renal artery denervation, using the second generation EnligHTN multi-electrode system significantly reduced office blood pressure from baseline to 1, 3, 6, 12, 18 and 24 months by 19/7, 26/9, 25/7, 23/7, 25/8 and 27/9 mmHg, respectively (p ≤ 0.0005). No serious device or procedure related adverse events affecting the renal arteries or renal function occurred through 24 months of follow-up. Renal sympathetic denervation using the second generation EnligHTN Renal Denervation System resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 24 months. Future studies will need to address the utility of this system against an appropriate sham based comparator.

Worthley SG ，Wilkins GT ，Webster MW ，Montarello JK ，Delacroix S ，Whitbourn RJ ，Warren RJ ... -  《-》

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

Worthley SG ，Tsioufis CP ，Worthley MI ，Sinhal A ，Chew DP ，Meredith IT ，Malaiapan Y ，Papademetriou V ... -  《-》