Axel Schmid

Renal Denervation in Moderate Treatment-Resistant Hypertension

OBJECTIVES This study sought to investigate the effect of renal denervation (RDN) in patients with treatment-resistant hypertension according to the established definition (Joint National Committee VII and European Society of Hypertension/European Society of Cardiology guidelines), that is, office blood pressure (BP) ≥140/90 mm Hg (with at least three antihypertensive drugs, including a diuretic, in adequate doses) and confirmed by 24-h ambulatory BP monitoring (ABPM). BACKGROUND RDN emerged as an innovative interventional antihypertensive therapy. However, so far, only patients with severe hypertension (systolic BP ≥160 mm Hg or ≥150 mm Hg for patients with type 2 diabetes) have been investigated. METHODS In this study, there were 54 patients with moderate treatment-resistant hypertension (office BP ≥140/90 mm Hg and <160/100 mm Hg and diagnosis confirmed by 24-h ABPM of ≥130/80 mm Hg) who underwent catheter-based RDN using the Symplicity catheter (Medtronic Inc., Mountain View, California). RESULTS Patients were treated with 5.1 ± 1.4 antihypertensive drugs on average. Office BP was significantly reduced by 13/7 mm Hg 6 months after RDN (systolic: 151 ± 6 mm Hg vs. 138 ± 21 mm Hg, p < 0.001; diastolic: 83 ± 11 mm Hg vs. 75 ± 11 mm Hg, p < 0.001). In patients (n = 36) who underwent ABPM 6 months after treatment, there was a reduction in average 24-h ABPM by 14/7 mm Hg (systolic: 150 ± 16 mm Hg vs. 136 ± 16 mm Hg, p < 0.001; diastolic: 83 ± 10 mm Hg vs. 76 ± 10 mm Hg, p < 0.001). In 51% of patients, office BP was controlled below 140/90 mm Hg after RDN. In addition, heart rate decreased from 67 ± 11 to 63 ± 10 beats/min (p = 0.006). CONCLUSIONS Our data indicate that RDN may reduce office and 24-h ambulatory BP substantially in patients with moderate treatment-resistant hypertension. (Renal Denervation in Treatment Resistant Hypertension; NCT01687725).

Attenuation-based automatic kilovolt selection in abdominal computed tomography: effects on radiation exposure and image quality.

ObjectivesDose reduction has become a major issue in computed tomography (CT). The benefit of kilovolt (kV) reduction has been demonstrated in CT angiography. We sought to evaluate an attenuation-based fully automated kV-selection and milliampere second-adaption algorithm for CT and to assess radiation dose and image quality in comparison with a standard 120 kV protocol in contrast-enhanced (CE) portal-venous thoracoabdominal imaging. Materials and MethodsOne hundred patients (mean age, 58.4 ± 5.7 years; mean body mass index [BMI], 26.1 ± 5.1 kg/m2) underwent CE CT using automated selection of the tube potential (80-140 kV) with milliampere second adaption based on the attenuation profile of the scout scan.The estimated CT dose index was recorded for the proposed scan setting and standard 120-kV protocol. Regions of interest measurements were performed at different locations for objective assessment of image quality. Signal-to-noise ratio and contrast-to-noise ratio (CNR) were calculated. The subjective image quality was assessed by 2 observers with a 4-point scale using previous CT examinations with the 120-kV standard protocol as the reference for comparison. ResultsThe kV-selection algorithm could be applied in all examinations without problems. Image quality was high, and there were no significant differences compared with previous examinations of the patients performed at 120 kV. Eighty kilovolts was used in 9% of examinations (mean BMI, 22.8 ± 2.8 kg/m2); 100 kV, in 75% (mean BMI, 23.7 ± 4.7 kg/m2); 120 kV, in 16% (mean BMI, 30 ± 3.3 kg/m2); and 140 kV, in a single case (BMI, 49.4 kg/m2). The average estimated CT dose index reduction was 25.3% in the 80-kV group, 14.5% in the 100-kV group, and 11.4% overall. The CNR did not differ significantly, whereas the signal-to-noise ratio was significantly higher in the 80- and 100-kV examinations. ConclusionThe attenuation-based kV-selection algorithm was demonstrated to be applicable in clinical routine of CE thoracoabdominal CT, to keep CNR constant, and to result in a significant dose reduction while preserving image quality.

Improvement of albuminuria after renal denervation

OBJECTIVES The primary objective of this study was the effect of renal denervation (RDN) on elevated urinary albumin-to-creatinine ratio (UACR) in treatment-resistant hypertensive patients. In addition, patients were stratified according their UACR at baseline into micro- (30-300 mg/g, n=37) and macroalbuminuria (≥ 300 mg/g, <2,200 mg/g, n=22). BACKGROUND Increased albuminuria indicates cardiovascular and renal damage in hypertension. RDN emerged as an innovative interventional approach to reduce blood pressure (BP) and may thus reduce albumin urinary excretion. METHODS Fifty-nine treatment-resistant hypertensive patients with elevated UACR at baseline underwent catheter-based RDN using the Symplicity Flex™ catheter (Medtronic Inc., Santa Rosa, CA). RESULTS In the whole and pre-specified subgroups both office and 24-h ambulatory BP were significantly reduced 6 months after RDN. In parallel, a significant reduction in UACR occurred in all patients (160 (65-496) versus 89 (29-319) mg/g creatinine, p<0.001) and in both subgroups (microalbuminuria: 83 (49-153) versus 58 (17-113) mg/g creatinine, p=0.001; macroalbuminuria: (536 (434-1483) versus 478 (109-1080) mg/g creatinine, p<0.001). In accordance, the prevalence of micro- and macroalbuminuria decreased significantly. Regression analysis revealed a modest positive relationship between the decrease of UACR and the fall of systolic BP (β=0.340, p=0.039) independent of renal function. Renal function remained unchanged after RDN. CONCLUSIONS In summary, following RDN, the magnitude of albuminuria as well as the prevalence of micro- and macroalbuminuria decreased in treatment-resistant hypertensive patients. Since albuminuria is an independent renal and cardiovascular risk factor, our findings suggest a reduction of renal and cardiovascular risk in these patients.

Vascular and Renal Hemodynamic Changes after Renal Denervation

BACKGROUND AND OBJECTIVES Renal denervation (RDN) has been shown to be effective in reducing BP in treatment-resistant hypertension. Measurement of the renal and sympathetic activity revealed a decrease in sympathetic drive to the kidney and small resistance vessels after RDN. However, the consequences on renal perfusion and renal vascular resistance (RVR), as well as central hemodynamics, are unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Nineteen patients with treatment-resistant hypertension (office BP≥140/90 mmHg, despite at least three antihypertensive drugs [including a diuretic], and diagnosis confirmed by 24-hour ambulatory BP monitoring) underwent RDN between January and October 2011. Renal perfusion and RVR were noninvasively assessed by magnetic resonance imaging with arterial spin labeling, and renal function was assessed by estimating GFR before (day -1), after (day +1), and again after 3 months of RDN. Central hemodynamics was assessed using pulse wave analysis at day -1 and after 6 months of RDN. RESULTS Peripheral office BP (systolic, 158±26 versus 142±23 mmHg, P=0.002; diastolic, 83±13 versus 76±9 mmHg, P=0.02) and mean systolic 24-hour ambulatory BP (159±17 versus 152±17 mmHg, P=0.02) were significantly reduced 6 months after RDN. Renal perfusion was not statistically different between day -1 and day +1 (256.8 [interquartile range (IQR), 241-278] versus 263.4 [IQR, 252-277] ml/min per 100 g; P=0.17) as well as after 3 months (256.8 [IQR, 241-278] versus 261.2 [IQR, 240-285] ml/min per 100 g; P=0.27) after RDN. RVR dropped (432.1 [IQR, 359-525] versus 390.6 [IQR, 338-461] AU; P=0.02), whereas renal function was not statistically different at any time point. Central systolic BP (145±31 versus 131±28 mmHg; P=0.009), diastolic BP (85±18 versus 80±14 mmHg; P=0.03), and central pulse pressure (61±18 versus 52±18 mmHg; P=0.02) were significantly reduced 6 months after RDN. Central augmentation index (24±8 versus 20±8%; P=0.02) was decreased 6 months after RDN. CONCLUSION The data indicate that RDN significantly reduced peripheral and central BP. Despite reduced systemic BP, renal perfusion and function did not change after RDN.

Renal Denervation in a Hypertensive Patient With End‐Stage Renal Disease and Small Arteries: A Direction for Future Research

J Clin Hypertens (Greenwich). 2012;14:799–801. ©2012 Wiley Periodicals, Inc.

Adherence to Antihypertensive Medication in Treatment‐Resistant Hypertension Undergoing Renal Denervation

Background Adherence to medication has been repeatedly proposed to represent a major cause of treatment‐resistant hypertension (TRH); however, treatment decisions such as treating TRH with renal denervation depend on accurate judgment of adherence. We carefully analyzed adherence rates to medication before and after renal denervation and its effect on blood pressure (BP) control. Methods and Results Eighty patients with TRH were included in 2 prospective observational studies that assessed the difference of potential antihypertensive and nephroprotective effects of renal denervation. To compare prescribed with actual medication intake (representing a measure of adherence), we analyzed urine samples collected at baseline and at 6 months after renal denervation for antihypertensive compounds or metabolites (by liquid chromatography–mass spectrometry). In addition to office BP, 24‐hour ambulatory BP and central hemodynamics (central systolic pressure, central pulse pressure) were assessed. Informed consent for analyses of urine metabolites was obtained from 79 of 80 patients. Actual intake of all antihypertensive drugs was detected at baseline and at 6 months after renal denervation in 44 (56%) and 52 (66%) patients, respectively; 1 drug was missing in 22 (28%) and 17 (22%) patients, respectively, and ≥2 drugs were missing in 13 (16%) and 10 (13%) patients, respectively. At baseline, 24‐hour ambulatory BP (P=0.049) and central systolic BP (P=0.012) were higher in nonadherent patients. Adherence did not significantly change overall (McNemar‐Bowker test, P=0.362). An increase in adherence was observed in 21 patients, and a decrease was observed in 11 patients. The decrease in 24‐hour ambulatory BP was not different in those with stable adherence 6 months after renal denervation (n=41, −7±13 mm Hg) compared with those with increased adherence (n=21, −10±13 mm Hg) and decreased adherence (n=11, −7±14 mm Hg) (P>0.20). Our study is limited by the relatively small sample size and potentially by the specific health environment of our university center (Northern Bavaria, Germany). Conclusions Nonadherence to medication among patients with TRH was relatively low: ≈1 of 6 patients with TRH did not take ≥2 of the prescribed drugs. Adherence pattern did not change significantly after renal denervation and had no impact on the overall observed BP changes, supporting the concept that renal denervation is an effective treatment in patients with TRH. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00888433, NCT01442883 and NCT01687725.

A heart within the heart: double-chambered left ventricle.

We describe a rare congenital anomaly in a 49-year-old woman who presented with palpitations and slightly reduced exercise capacity. A double-chambered left ventricle was suspected on echocardiography and confirmed by cardiac computed tomography scanning, cardiac magnet resonance imaging, and invasive angiography.

Immediate changes of angiosome perfusion during tibial angioplasty.

Objective: In recent years, a controversial discussion about the clinical relevance of the angiosome concept during tibial angioplasty has developed. Therefore, we conducted a prospective study to evaluate the angiosome concept on the level of microcirculation during tibial vascular interventions. Methods: Thirty patients with isolated tibial angioplasty were examined prospectively. Macrocirculation was evaluated by measurement of the ankle‐brachial index (ABI). For the assessment of microcirculation, a combined method of laser Doppler flowmetry and tissue spectrometry (O2C; LEA Medizintechnik GmbH, Giessen, Germany) was applied. Microcirculatory parameters were measured continuously during the procedures. Measuring points were located over different angiosomes of the index foot; a control probe was placed on the contralateral leg. Results: Cumulated microcirculation parameters (sO2, flow) as well as the ABI showed a significant improvement postinterventionally (ABI, P < .001; sO2, P < .001; flow, P < .001). Assessment of the separate angiosomes of the index leg and the comparison of the directly revascularized (DR) and indirectly revascularized (IR) angiosomes showed no significant difference concerning the microperfusion postinterventionally (DR − IR: sO2, P = .399; flow, P = .909) as well as during angioplasty. Even a further subdivision of the collective into patients with diabetes (sO2, P = .445; flow, P =.758) and renal insufficiency (sO2, P = .246; flow, P = .691) could not demonstrate a superiority of the direct revascularization at the level of microcirculation in these patients (comparison DR − IR). Conclusions: There is a significant overall improvement in tissue perfusion of the foot immediately after tibial angioplasty. The effect shown in this study, however, was found to be global and was not restricted to certain borders, such as defined by angiosomes.

Renal Artery Denervation for the Treatment of Hypertension: Opening up New Horizons

Hypertension is a major global public health concern. Anestimated 30–40% of the adult population in the developedworld suffer from this condition [1, 2]. Currently the role ofinterventional radiology is limited to the few cases inwhich the renin–angiotensin–aldosterone system is acti-vated by renal artery stenosis. However, stenosis of therenal artery accounts for elevated blood pressure in much\5% of patients, and the effect of renal stenting on bloodpressure is not as high as expected in the past [3, 4]. In themajority of patients, hypertension is deemed ‘‘essential,’’meaning that no direct cause can be identified and it isbelieved to be related to both genetic disposition andenvironmental influences. These patients need lifelongpharmacological therapy. Despite a plethora of antihyper-tensive drugs, hypertension remains resistant in a consid-erable number of patients. A new interventional procedure,the catheter-based renal sympathetic denervation (RSD),promises help in such cases of resistant hypertension.There is increasing evidence that renal efferent sympa-thetic nerves and afferent sensory nerves that lie within andimmediately adjacent to the wall of the renal artery arecrucial for initiation and maintenance of systemic hyper-tension [5–8]. Efferent renal sympathetic activation leadsto volume retention via sodium reabsorption, a reduction ofrenal blood flow by pre- and postglomerular vasocon-striction, and activation of the renin–angiotensin–aldosterone system. Afferent renal sensory nerve activitydirectly influences sympathetic outflow from the centralnervous system to the kidneys and other highly innervatedorgans involved in cardiovascular control, such as the heartand peripheral blood vessels, by modulating hypothalamicactivity [9]. Hence, functional denervation of the humankidney by targeting both efferent sympathetic nerves andafferent sensory nerves seems to be a valuable treatmentstrategy for hypertension [10].Renal denervation has been used successfully as atherapeutic strategy to prevent hypertension in a variety ofexperimental models. In humans, radical surgical methodsfor thoracic, abdominal, and pelvic sympathetic denerva-tion were successfully applied as early as the 1930s tolower blood pressure in patients with malignant hyperten-sion. However, the so-called Smithwick intervention wasassociated with high perioperative morbidity and mortalityand long-term complications, such as bowel, bladder, anderectile dysfunction, and severe postural hypotension[11–13].For RSD, the treatment catheter (Symplicity, Ardian,Inc., Palo Alto, CA) is introduced into the renal artery viafemoral access. Radiofrequency ablations lasting up to2 min each are applied to four to six discrete points in therenal artery. To destroy the nerve tissue in the whole cir-cumference of the artery, the tip of the ablation wire has tobe pulled in a helical manner backward toward the renalartery ostium by 5-mm steps between each ablation. Thetreatment is analogical to the radiofrequency ablation ofaberrant nerve bundles in the heart, which has been per-formed for many years. At first for safety reasons, theprocedure was only performed on one artery per session.After establishing the safety of the technique, a simulta-neous bilateral renal artery denervation is normally per-formed [14].

Transvenous Renal Transplant Biopsy via a Transfemoral Approach.

Percutaneous renal biopsy (PRB) of kidney transplants might be prevented by an elevated risk of bleeding or limited access to the allograft. In the following, we describe our initial experience with 71 transvenous renal transplant biopsies in 53 consecutive patients with unexplained reduced graft function who were considered unsuitable candidates for PRB (4.2% of all renal transplant biopsies at our institution). Biopsies were performed via the ipsilateral femoral vein with a renal biopsy set designed for transjugular renal biopsy (TJRB) of native kidneys. Positioning of the biopsy system within the transplant vein was achievable in 58 of 71 (81.7%) procedures. The specimen contained a median of 10 glomeruli (range 0–38). Tissue was considered as adequate for diagnosis in 56 of 57 (98.2%) biopsies. With respect to BANFF 50.9% of the specimen were adequate (>10 glomeruli), 47.4% marginally adequate (1–9 glomeruli) and 1.8% inadequate (no glomeruli). After implementation of real‐time assessment all specimen contained glomeruli. One of the fifty‐eight (1.8%) procedure‐related major complications occurred (hydronephrosis requiring nephrostomy due to gross hematuria). Transfemoral renal transplant biopsy (TFRTB) is feasible and appears to be safe compared to PRB. It offers a useful new alternative for histological evaluation of graft dysfunction in selected patients with contraindications to PRB.