Klaas Franzen

Catheter-based renal sympathetic denervation improves central hemodynamics and arterial stiffness: a pilot study.

J Clin Hypertens (Greenwich). 2012;14:861–870. ©2012 Wiley Periodicals, Inc.

Improved Heart Rate Dynamics in Patients Undergoing Percutaneous Renal Denervation

Autonomic sympathetic activation plays a key role in the pathophysiology of systemic hypertension and left ventricular hypertrophy. As shown in the Symplicity HTN-1 and HTN-2 trials, percutaneous renal denervation (PRD) has proven to be an effective and safe method to treat patients with medically resistant hypertension and is considered to influence central sympathetic tone. In patients after renal denervation, microneurography showed a gradual reduction in muscle sympathetic nerve activity in accordance with a modulation of central sympathetic tone. The effect on cardiac autonomic tone is not known. Heart rate variability (HRV) is a marker of cardiac autonomic activity. The present study assessed for the first time the effect of sympathetic renal denervation on heart rate dynamics in patients. This prospective single-center study was approved by the local ethics committee. All patients provided written informed consent. For inclusion, patients had to be older than 18 years with a systolic office blood pressure (BP) 150 mm Hg despite intake of 3 antihypertensive drugs, including one diuretic. Exclusion criteria were secondary causes of hypertension, reduced renal function (glomerular filtration rate <45 mL ⁄ min ⁄ 1.73 m), atrial fibrillation, pacemaker rhythm, and pregnancy. Patients with significant renal artery stenosis, abnormalities of renal artery anatomy, or a history of prior renal artery intervention were excluded from the study. Eligible patients had to document home BPs 3 times daily. Medication was maintained in all patients throughout follow-up and changes were made only when symptomatic low BP occurred. In 14 patients, Holter electrocardiographic recordings were analyzed for time and frequency domain HRV parameters before and 3 months after percutaneous renal sympathetic denervation. Twentyfour–hour electrocardiographic (ECG) recordings were performed using 3-channel Holter recorders (LifeCard CF, Spacelabs; Delmar Reynolds, Hertford, UK) at a sampling rate of 1024 Hz. Office BP measurements

Successful Single-Sided Renal Denervation Approach in a Patient With Stenosis of an Accessory Renal Artery

Sympathetic overactivity has been implicated in the pathophysiology of systemic hypertension. As shown in randomized controlled trials, percutaneous renal denervation has been proven to be an effective and safe method to treat patients with resistant hypertension. In present trials, patients with significant renal artery stenosis or abnormalities in renal artery anatomy or a history of prior renal artery intervention were excluded. Thus, no data exist regarding renal denervation in patients with accessory renal artery. Here, we report a single-sided renal denervation in an 83-year-old woman (weight, 70 kg; height, 152 cm) with contralateral accessory renal artery, who experienced medically resistant hypertension despite intake of 7 antihypertensive drugs. The patient fulfilled inclusion criteria of the Symplicity HTN-1 and HTN-2 trials. Secondary causes for hypertension were excluded including sleep apnea syndrome. The patient did not have diabetes, renal failure, or coronary heart disease. The patient was required to record automated home blood pressure (BP) measurements 3 times daily for periods of 7 days before and 1 and 3 months after renal denervation. Antihypertensive medication was maintained unchanged throughout follow-up. Baseline systolic ⁄ diastolic BP was 173 22 mm Hg ⁄ 86 14 mm Hg. For renal denervation, the femoral artery was accessed in standard technique and fluoroscopic angiography was performed to visualize the renal artery. Angiography revealed normal configuration of left renal artery, where denervation was performed with application of 5 low-power radiofrequency treatments along the proximal portion of the vessel. Mean temperature was 48 3 C during 120 seconds of ablation at each point. On the right side, angiography revealed a cranial accessory renal artery with high ostial stenosis. The caudal renal artery showed a diameter of <4 mm precluding an ablation procedure. Because of a rather small renal artery diameter, stenting was not performed. In result, only left single-sided renal denervation was performed. After denervation, renal function assessed by serum creatinine was unchanged (baseline 74.9 lmol ⁄ L vs after 3 months 84.2 lmol ⁄ L). Single-sided renal denervation resulted in moderate office BP reduction 1 month after the procedure (173 22 mm Hg vs 162 20 mm Hg; not significant). Significant systolic BP changes were seen at 3 months follow-up of 14% (173 22 mm Hg vs 148 15 mm Hg; P<.001). Diastolic BP did not change significantly over time (86 14 mm Hg vs 83 9 mm Hg [1 month] and vs 83 9 mm Hg [3 months]). No adverse events were observed. Our case report supports previous data on effective and significant BP reduction after renal denervation in patients with medically resistant hypertension. We describe here for the first time successful one-sided sympathetic renal denervation in a patient with an accessory renal artery showing a relevant stenosis of the ostium. Systolic BP reduction of 25 mm Hg after 3 months was comparable to the results in the randomized Symplicity HTN-1 and HTN-2 controlled trials. However, our patient had nonsignificant changes in systolic BP after 1 month and was not affected in diastolic parameters. This observation underlines the individual response of renal denervation in patients with resistant hypertension. Accessory renal arteries originating directly from the aorta were found in 25% to 50% of normal patients at autopsy. The accessory renal arteries were often narrower than main renal arteries. There are conflicting data whether accessory renal arteries lead to systemic arterial hypertension by activation of the renin-angiotensin system as a consequence of lower perfusion pressure and higher resistance across the accessory artery. In the present case, we found an additional, significant stenosis of the accessory renal artery. The estimated incidence of accessory renal artery stenosis ranges from 1.5% in a catheter angiography study (n=68) to 2.2% in a magnetic resonance angiography study (n=45). Controversial data suggested either transcatheter angioplasty or interventional occlusion of accessory renal arteries to treat hypertension linked to this abnormality. Gupta and Tello concluded in their study that accessory renal arteries are not associated with an increased risk of hypertension development. In our patient, we performed renal denervation only on the side with normal renal anatomy and not on the side with the accessory renal artery. Also, no dilatation or stenting of the accessory renal artery stenosis was performed due to small vessel diameter. Yet, follow-up showed a significant reduction in BP. We therefore conclude that in select patients, single-sided renal denervation may be an acceptable approach to treat resistant hypertension. Furthermore, our data support the hypothesis that accessory renal arteries may not be causative for resistant hypertension.

Central hemodynamics and arterial stiffness during the finals of the world cup soccer championship 2010.

BACKGROUND Emotional stress is considered a risk factor for cardiovascular events, the underlying pathophysiology remains unclear. METHODS To evaluate how emotional stress effects hemodynamics, thirteen healthy German soccer fans (mean 37.6 years, 24-56 years) were studied during live TV coverage of the finals with German national team participation (GP) and the respective finals without German participation (noGP). Peripheral blood pressure, heart rate, central blood pressure, augmentation pressure and index, cardiac output and peripheral resistance were measured. RESULTS In the 1st hour before the match all parameters were not significantly different between the groups. In the GP group peripheral systolic pressure (1st halftime noGP 118 ± 1(s.e.m) versus GP 126 ± 2 mmHg, p<0.05, 2nd 117 ± 1 vs. 125 ± 2 mmHg, p<0.05), mean blood pressure, diastolic blood pressure, heart rate (1st 73 ± 2 vs. 86 ± 3 bpm, p<0.05, 2nd 75 ± 2 vs. 87 ± 2 bpm, p<0.05), cardiac output (1st 4,4 ± 0,1 versus 4,8 ± 0,1L/min, p<0.05, 2nd 4,6 ± 0,1 versus 4,7 ± 0,11 L/min, p>0.05) and peripheral resistance were significantly increased compared to the noGP group during the matches. Systolic central aortic pressure (noGP: 101 ± 2 versus GP 107 ± 2 mmHg, p<0.05) and central pulse pressure (noGP: 31.3 ± 1.3 mmHg vs. GP: 38.5 ± 2.7 mmHg, p<0,05) remained elevated during the second hour after the match. CONCLUSIONS We observed persistent changes in central hemodynamics 2h after emotional stress. Despite normalization of peripheral values after the end of the finals, we observed prolonged elevation of central systolic blood and pulse pressure. Our findings contribute to the understanding of the increased risk of cardiovascular events in emotional stress.

E-cigarettes and cigarettes worsen peripheral and central hemodynamics as well as arterial stiffness: A randomized, double-blinded pilot study:

The introduction of electronic cigarettes has led to widespread discussion on the cardiovascular risks compared to conventional smoking. We therefore conducted a randomized cross-over study of the acute use of three tobacco products, including a control group using a nicotine-free liquid. Fifteen active smokers were studied during and after smoking either a cigarette or an electronic cigarette with or without nicotine (eGo-T CE4 vaporizer). Subjects were blinded to the nicotine content of the electronic cigarette and were followed up for 2 hours after smoking a cigarette or vaping an electronic cigarette. Peripheral and central blood pressures as well as parameters of arterial stiffness were measured by a Mobil-O-Graph® device. The peripheral systolic blood pressure rose significantly for approximately 45 minutes after vaping nicotine-containing liquid (p<0.05) and for approximately 15 minutes after smoking a conventional cigarette (p<0.01), whereas nicotine-free liquids did not lead to significant changes during the first hour of follow-up. Likewise, heart rate remained elevated approximately 45 minutes after vaping an electronic cigarette with nicotine-containing liquid and over the first 30 minutes after smoking a cigarette in contrast to controls. Elevation of pulse wave velocity was independent from mean arterial pressure as well as heart rate in the electronic cigarette and cigarette groups. In this first of its kind trial, we observed changes in peripheral and central blood pressure and also in pulse wave velocity after smoking a cigarette as well as after vaping a nicotine-containing electronic cigarette. These findings may be associated with an increased long-term cardiovascular risk.

Biomarker response and therapy prediction in renal denervation therapy - the role of MR-proadrenomedullin in a multicenter approach.

Abstract Background: Renal denervation has been proposed as a therapeutic option in patients with resistant hypertension. Circulating blood borne biomarkers might be helpful to identify individuals responding to RDN therapy. MR-proADM is a strong prognostic marker in patients with cardiovascular disease. The aim of this multicenter study was to evaluate the effect of RDN on MR-proADM concentrations. Methods and results: We measured MR-proADM, BNP, and MR-proANP in 110 patients before and after RDN in a multicenter setting. All patients were followed up after 1 and 6 months by office and ambulatory blood pressure (BP) measurements. The mean office BP decreased from 165/89 to 152/87 mmHg 6 months after RDN (systolic: p < 0.001; diastolic: ns), the responder-rate was 74%. Intriguingly MR-proADM concentrations increased from 0.66 to 0.69 nmol/L (p < 0.001) and were significantly associated with reduction of systolic office BP after 6 months in multivariate analyses (coefficient −0.0018, p < 0.001). In therapy-responders MR-proADM concentrations showed a significantly higher increase over time (coefficient 0.0105, p < 0.05), as compared to non-responders. There were no significant differences in BP change for individuals with low and high baseline MR-proADM (BP-Delta low MR-proADM −23/−4 mmHg vs. high MR-proADM −24/−5 mmHg). The natriuretic biomarkers BNP and MR-proANP did not change significantly after 6 months. Biomarkers at baseline were not able to predict for therapy-responder. Conclusion: In patients undergoing RDN, baseline measurements of various biomarkers had no prognostic use for therapy success in this short time follow-up period in a multicenter approach. Intriguingly, MR-proADM showed a significant association with BP reduction after 6 months.

Renal denervation - a clinical update and future directions.

The aim of this review is to give a contemporary update on renal denervation therapy focusing particularly on the scientific background and present literature as well as on different technical approaches and potential future directions.

Renal denervation improves 24-hour central and peripheral blood pressures, arterial stiffness, and peripheral resistance

Ambulatory blood pressure (BP) and central BP are better predictors for overall cardiovascular risk and mortality than brachial BP. Renal denervation (RDN) has been shown to reduce office brachial and central BP as well as brachial ambulatory BP, but data on central ambulatory BP are limited. Patients (N = 94) with treatment resistant hypertension (TRH) who underwent RDN were included. Ambulatory BP, including central pressures, hemodynamics, and arterial stiffness were measured at baseline and 3, 6, 12 months after RDN by an oscillometric device (MobiloGraph™). At 3, 6, and 12‐month follow‐ups, brachial ambulatory BP was reduced (P for all < .001). Consistently, central ambulatory BP was reduced (P for all < .001). Ambulatory assessed averaged daytime pulse wave velocity improved after RDN (P < .05). Total vascular resistance decreased (P for all < .01). In patients with TRH, RDN improves brachial and central ambulatory BP, arterial stiffness, and total vascular resistance, indicating an improvement of cardiovascular outcome.