Zuzana Krátká

Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension: One-Year Outcomes of Randomized PRAGUE-15 Study.

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.

Renal denervation in comparison with intensified pharmacotherapy in true resistant hypertension: 2-year outcomes of randomized Prague-15 study

Objectives: The randomized, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month data. Methods: A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline SBP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after 1 year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in five patients. Results: Similar and comparable reduction of 24-h SBP after RDN or spironolactone addition after randomization was observed, 9.1 mmHg (P = 0.001) and 10.9 mmHg (P = 0.001), respectively. Similar decrease of office blood pressure (BP) was observed, 17.7 mmHg (P < 0.001) versus 14.1 mmHg (P < 0.001), whereas the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed nonsignificantly better efficacy of spironolactone addition in 24-h SBP and office SBP reduction than RDN (3.7 mmHg, P = 0.27 and 4.6 mmHg, P = 0.28 in favour of spironolactone addition, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, P = 0.001). Conclusion: In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in BP reduction over a period of 24 months. However, by contrast to the 12-month results, BP changes were not significantly greater.

Long-Term Effect of Adrenalectomy on Cardiovascular Remodeling in Patients With Pheochromocytoma

Context Catecholamines may contribute to the accumulation of collagen fibers and extracellular matrix in the arterial and myocardial wall due to various mechanisms. Reversibility of this process has not been studied on both structures simultaneously. Objective To clarify the long-term effect of excess normalization of catecholamines on carotid and myocardial wall changes in patients with pheochromocytoma or functional paraganglioma (PHEO) after tumor removal. Design, Settings, and Patients Carotid intima-media thickness (IMT) and the left ventricular (LV) mass index were studied in 50 patients with PHEO before tumor removal and 5 years after tumor removal, and in 50 blood pressure- and age-matched essential hypertensive patients before follow-up and after 5 years of follow-up. Main Outcome Measures Common carotid artery (CCA)-IMT and LV mass indexed to lean body mass (LBM). Results Elimination of catecholamine excess in the PHEO group resulted in a significant decrease in CCA-IMT and LV mass index from 0.86 ± 0.17 to 0.83 ± 0.18 mm (P < 0.05) and from 3.2 ± 0.9 to 2.9 ± 0.9 g/LBM (P < 0.001), respectively. In contrast, CCA-IMT and LV mass index increased significantly from 0.78 ± 0.14 to 0.81 ± 0.15 mm (P < 0.05) and from 3.1 ± 0.7 to 3.2 ± 0.6 g/LBM (P < 0.05), respectively, in patients with essential hypertension. Conclusion In patients with PHEO, carotid IMT and LV mass index can significantly regress after tumor removal, in contrast to the impairment of these parameters in essential hypertensive patients during the same long-term period.

Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.

PREDICTION OF LONG-TERM RENAL DENERVATION EFFICACY

Objective: Diversity of blood pressure response and great variability within studies emphasise the need to identify predictors of renal denervation efficacy. Previous studies identified various predictors within periods of 3–6 months. Design and method: The goal of the current study is to examine the possible predictors of sustained decline of blood pressure after renal denervation in a long-term period of 2 years. Evaluated patients were either randomised in the original Prague-15 study or were pilot patients, meeting the same inclusion criteria of true-resistant hypertension. Patients were considered as responsive when the decline of 24 h systolic blood pressure > 10 mmHg was present 6, 12 and 24 months after the procedure. In addition, analysis for separate visits was performed. Denervation was performed using the unipolar Symplicity® Renal Denervation System. Extensive assessment of computed tomography angiography by numerous measurements including morphology of the renal arteries was performed. Results: A total of 48 patients were analysed with 27 patients suitable for long-term prediction. According to the protocol of the study, spironolactone was added at 12-month follow-up as a crossover and these patients were excluded from long-term analysis. Five of the 27 patients were identified as long-term responders with average 24 h blood pressure decline of 20/9 mmHg. Strongest predictors of BP decline were higher baseline 24 h systolic blood pressure (p = 0.01) and higher diameter of the left renal artery (p = 0.04). Conclusions: Only a minority of denervated patients exhibited sustained blood pressure decline. Higher baseline blood pressure and higher renal artery diameter were the strongest predictors. Our findings thus might theoretically support the actual hypothesis of the necessity to ablate the distal parts of the renal artery (these conditions might allow such ablation to be performed).

[PP.05.36] RENAL DENERVATION IN COMPARISON TO INTENSIFIED PHARMACOTHERAPY IN TRUE RESISTANT HYPERTENSION. TWO-YEAR OUTCOMES OF RANDOMISED PRAGUE-15 STUDY

Objective: This randomised, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month data. Figure. No caption available. Design and method: A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomised to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after one year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in 5 patients. Results: Similar and comparable reduction of 24-hour systolic blood pressure after RDN or spironolactone addition after randomisation was observed, 9.1 mmHg (p = 0.001) and 10.9 mmHg (p = 0.001), respectively. Similar decrease of office blood pressure was observed, 17.7 mmHg (p < 0.001) versus 14.1 mmHg (p < 0.001), while the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed non-significantly better efficacy of spironolactone addition in 24 h systolic and office systolic blood pressure reduction than RDN (3.7 mmHg, p = 0.27 and 4.6 mmHg in favour of spironolactone addition, p = 0.28, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, p = 0.001). Conclusions: In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in blood pressure reduction over a period of 24 months. However, by contrast to the 12-month results, blood pressure changes are not significantly greater.

[PP.27.12] DIFFERENCES BETWEEN HYPERMETABOLIC AND NORMOMETABOLIC PHEOCHROMOCYTOMA

Objective: The aim of the study was to evaluate differences between patients with pheochromocytoma presenting with hypermetabolism and normometabolism according to resting energy expenditure (REE), and to estimate factors affecting metabolic state. Design and method: We have measured REE in 34 patients (17 women) with pheochromocytoma by indirect calorimeter (Vmax-Encore 29N system) before adrenalectomy. The hypermetabolic state was defined as measured REE above 10% higher than the predicted value. Body fat percentage was measured by Bodystat device. The diagnosis of PHEO was based on plasma metanephrines and the demonstration of tumor by CT scan. The diagnose was confirmed histopathologically. Results: The hypermetabolic state was confirmed in 16 patients with pheochromocytoma (47%). Hypermetabolism was more frequent in patients with adrenergic phenotype. Hypermetabolic state was characterized by higher age (56 ± 13 vs 48 ± 15 years, P = 0.07), serum cholesterol levels (4.1 ± 0.9 vs 5.1 ± 1.0 mmol/l, P = 0.005), especially LDL (P = 0.006) and serum chromogranin A levels (P = 0.041) in comparison with normometabolic pheochromocytoma. No differences were found in BMI, body fat percentage, blood pressure, glucose levels, TSH, plasma normetanephrine levels and pharmacotherapy. No significant correlations between calorimetry parameters and hormones were detected. Conclusions: Chronic catecholamine overproduction in pheochromocytoma may lead to a proinflammatory and hypermetabolic state characterized by increased REE. A hypermetabolic state was found in 47% patients with pheochromocytoma and was more common in older patients with adrenergic phenotype and higher chromogranin A levels as a possible indicator of disease activity. We did not observe a correlation between catecholamine metabolites and calorimetry parameters.

[OP.7D.09] THE ROLE OF ADDING SPIRONOLACTONE AND RENAL DENERVATION IN TRUE RESISTANT HYPERTENSION. ONE-YEAR OUTCOMES OF RANDOMIZED PRAGUE-15 STUDY

Objective: This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension (TRH) and assessed the effect of spironolactone addition. We present the 12-month data. Design and method: The entry criteria included office systolic blood pressure (BP) over 140 mmHg, ambulatory 24-hour mean systolic BP over 130 mmHg, treatment with at least 3 antihypertensive drugs including a diuretic, exclusion of secondary hypertension and excluding drug non-compliance. Thus, only patients with TRH were included after thorough examination in three tertiary hypertension centers. After randomization, patients selected for RDN were maintained on baseline medical therapy for 1 year unless changes were considered clinically necessary. Patients selected for intensified medical treatment received baseline medical therapy plus spironolactone (25 mg daily, as generally recommended), if tolerated, and if no contraindications were present. Results: A total of 106 patients with TRH were randomized: 52 patients to RDN and 54 patients to the spironolactone addition, with baseline systolic BP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable 24-hour systolic BP decline of 6.4 mmHg, p = 0.001 in RDN versus 8.2 mmHg, p = 0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic BP decline between complete RDN (6.3 mmHg, p = 0.004) and the subgroup where spironolactone was added and this continued within the 12 months (15 mmHg, p = 0.003). See Figure. Renal artery CT angiograms before and after one year post-renal denervation did not reveal any relevant changes. Figure. No caption available. Conclusions: This study shows that, over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of TRH with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in BP reduction.

Role of Adding Spironolactone and Renal Denervation in True Resistant HypertensionNovelty and Significance: One-Year Outcomes of Randomized PRAGUE-15 Study

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.

Role of Adding Spironolactone and Renal Denervation in True Resistant HypertensionNovelty and Significance

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.