Predictors of blood pressure response after renal denervation beyond pretreatment blood pressure

Abstract Background The principle of initial value (Wilder's law of initial value) proposes that the “direction of response of body function to any agent depends to a large degree on the initial value of that function”. Indeed, in several trials on renal denervation (RDN), pre-treatment blood pressure (BP) has been consistently and repeatedly found to predict the decrease in BP after RDN. Efforts to discover further statistically significant and clinically meaningful predictors of BP response to RDN failed. Objective By use of a new methodological approach, we aimed to determine predictors of BP response after RDN in patients with resistant hypertension. Methods The study population comprised 266 patients with resistant hypertension (mean age 62 years, 34% females, mean BMI 30.5 kg/m2, 27% had coronary heart disease, 42% had diabetes mellitus and 61% had hypercholesterolaemia) who underwent radiofrequency RDN with the Symplicity catheter at the Universities of Homburg and Erlangen. Clinical data including 24h ambulatory BP (ABP) were obtained prior to, and 3, 6 and 12 months after RDN. The primary parameter of response was defined as change in 24-hour systolic ABP after 6 months from pre-treatment values. As expected, change in 24h systolic ABP correlated with pre-treatment 24h systolic ABP (r2 linear = 0.225, p<0.001), with change in 24h systolic ABP = 73.82 + 0.55 x pre-treatment 24h systolic ABP. To overcome the predominant role of the pre-treatment BP that may mask other factors, we calculated for each individual patient the “expected systolic ABP decrease” by applying this regression equation and the “excessive systolic ABP decrease” by subtracting the measured from expected change in 24h systolic ABP. We divided the study population into 2 groups (above [responders] and below [non-responders] of the median change in excessive 24h systolic ABP. Results Neither pre-treatment 24h systolic or diastolic ABP, nor office systolic or diastolic BP differed between the two groups (all p>0.20). Following RDN, 24h systolic ABP decreased in the responders by −23.3±16 vs non-responders +1.4±11 mmHg at 6 month, and 24h systolic ABP values were also significantly lower in responders at 3 and 12 months (all p<0.001), without difference in number of antihypertensive drugs between the groups. Of all clinical variables at baseline, office heart rate (65.6 vs 68.7±12 bpm, p=0.024) and HbA1c (6.07±0.88 vs. 6.37±1.23%, p=0.035) were lower in responders compared with non-responders. Finally, a multiple regression analysis confirmed that pre-treatment 24h systolic ABP (beta +0.565, p<0001), HbA1c (beta −0.167, p=0.004) and office HR (beta +0.106, p=0.057) were independent predictors of decrease in 24h systolic ABP. Conclusion In patients with resistant hypertension, lower HbA1c and office HR were identified as predictors of BP response in addition to pre-treatment BP. This finding may help to identify hypertensive patients who benefit most from RDN. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Extramural grant provided vy Medtronic INc

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MP107SALT INTAKE AND BLOOD PRESSURE RESPONSE TO PERCUTANEOUS RENAL DENERVATION IN RESISTANT HYPERTENSION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfx163.mp107 ◽

2017 ◽

Vol 32 (suppl_3) ◽

pp. iii467-iii467

Author(s):

Esther de Beus ◽

Michiel Bots ◽

Peter Blankestijn

Keyword(s):

Blood Pressure ◽

Resistant Hypertension ◽

Renal Denervation ◽

Blood Pressure Response ◽

Pressure Response

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Resistant Hypertension: A Real Entity Requiring Special Treatment?

European Cardiology Review ◽

10.15420/ecr.2016.11.1 ◽

2016 ◽

Vol 11 (1) ◽

pp. 8

Author(s):

Stefano Taddei ◽

Rosa Maria Bruno ◽

◽

Keyword(s):

Blood Pressure ◽

Resistant Hypertension ◽

Renal Denervation ◽

Antihypertensive Drugs ◽

Pressure Control ◽

Clinical Situation ◽

Special Treatment ◽

Separate Clinical Entity ◽

Real Entity ◽

Definition Of

Resistant hypertension (RH) was defined many years ago as a clinical situation in which blood pressure remains uncontrolled despite concomitant intake of at least three antihypertensive drugs (one of them preferably being a diuretic) at full doses. This operative definition was aimed at identifying a subset of hypertensive patients requiring a more extensive clinical workup in order to achieve an adequate blood pressure control. An oversimplification of this picture led to consider RH as a separate clinical entity requiring special, expensive treatments, such as renal denervation and baroreceptor activating therapy. In this review we will discuss the utility and the shortcomings of the definition of RH and the possible consequences for treatment.

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Non-pharmacological methods in the treatment of resistant hypertension

Folia Medica ◽

10.2478/v10153-011-0081-y ◽

2012 ◽

Vol 54 (2) ◽

pp. 5-12 ◽

Cited By ~ 2

Author(s):

Kostadin N. Kichukov ◽

Hristo V. Dimitrov ◽

Lora K. Nikolova ◽

Ivo S. Petrov ◽

Maria P. Tokmakova

Keyword(s):

Blood Pressure ◽

Resistant Hypertension ◽

Renal Denervation ◽

Antihypertensive Drugs ◽

Adult Population ◽

Clinical Problem ◽

Renal Sympathetic Denervation ◽

Great Promise ◽

Long Term Effects ◽

Blood Pressure Targets

ABSTRACT INTRODUCTION: Arterial hypertension is the most common chronic cardiovascular disease affecting about 25% of the adult population. Meta-analyses have demonstrated a linear relationship between blood pressure and the risk of cardiovascular events. Resistant hypertension defined as failure to reach blood pressure targets despite treatment with three antihypertensive drugs including a diuretic represents a serious clinical problem. It has been estimated that it affects between 8.9% and 12.8% of all treated hypertensive subjects. In resistant hypertension the optimal blood pressure is illusive despite very well tailored therapy. OBJECTIVE: Management of resistant hypertension is exactly the fi eld where blood pressurecontrolling non-pharmacological methods fi t best. The present article aims at throwing light on these methods’ principles of action, on who the target patient groups are and the respective results. Two methods are especially reviewed here: the carotid barorefl ex stimulation and the transcatheter renal sympathetic denervation. Current results from the use of renal denervation suggest stable effi ciency of the method, the results becoming signifi cant 6 months after the procedure is applied and sustained for two years in the follow-up. As much as 90% of the treated patients respond to the procedure. The transcatheter renal denervation is associated with only 2.61% of procedural complications. The barorefl ex carotid stimulation, too, is known to produce a stable effect on blood pressure: the effect become obvious at 12 months in 88% of the treated subjects. The neurologic complications associated with the procedure are reported to occur in 4.4% of cases. CONCLUSION: The present review article clearly demonstrates that non-pharmacological methods for treatment of resistant hypertension show great promise despite some open questions concerning their long term effects and procedural safety.

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[PP.23.22] CORRELATION CENTRAL BLOOD PRESSURE RESPONSE WITH CREATININ, EGFR AND HEART RATE AFTER RENAL DENERVATION IN PATIENTS WITH RESISTANT HYPERTENSION IN UKRAINE

Journal of Hypertension ◽

10.1097/01.hjh.0000492093.66024.00 ◽

2016 ◽

Vol 34 ◽

pp. e260

Author(s):

O. Rekovets ◽

Y. Sirenko ◽

A. Dobrokhod ◽

O. Torbas ◽

S. Kushnir ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Resistant Hypertension ◽

Renal Denervation ◽

Blood Pressure Response ◽

Pressure Response ◽

Central Blood Pressure

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Salt intake and blood pressure response to percutaneous renal denervation in resistant hypertension

Journal of Clinical Hypertension ◽

10.1111/jch.13085 ◽

2017 ◽

Vol 19 (11) ◽

pp. 1125-1133 ◽

Cited By ~ 1

Author(s):

Esther de Beus ◽

Rosa L. de Jager ◽

Martine M. Beeftink ◽

Margreet F. Sanders ◽

Wilko Spiering ◽

...

Keyword(s):

Blood Pressure ◽

Resistant Hypertension ◽

Renal Denervation ◽

Salt Intake ◽

Blood Pressure Response ◽

Pressure Response

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Renal Denervation Therapy (RDT) in Resistant Hypertension

BIRDEM Medical Journal ◽

10.3329/birdem.v2i2.12325 ◽

2012 ◽

Vol 2 (2) ◽

pp. 104-112

Author(s):

Mohammad Gaffar Amin ◽

Hasna Fahmima Haque

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Renal Artery ◽

Resistant Hypertension ◽

Renal Denervation ◽

Antihypertensive Drugs ◽

Antihypertensive Agents ◽

Radiofrequency Energy ◽

Sympathetic Nervous

Resistant hypertension is defined as blood pressure that remains above therapeutic goal despite the use of three antihypertensive drugs including a diuretic. As much as one third of patients with arterial hypertension are treatmentrefractory as they do not reach sufficient blood pressure control despite combination antihypertensive therapy of significant duration. The hyperactivity of sympathetic nervous system (SNS) in the occurrence of treatment-resistant long standing hypertension has been established both in animal models and in clinical practice. In these patients, the kidneys play a central role as an activator of the sympathetic nervous system. The failure of purely pharmacological approaches to treat resistant hypertension has stimulated interest in invasive device-based treatments based on old concepts. In the absence of orally active antihypertensive agents, patients with severe and complicated hypertension were widely treated by surgical denervation of the kidneys until the 1960s, but this approach was associated with a high incidence of severe adverse events and a high mortality rate. A new catheter system using radiofrequency energy has been developed, allowing an endovascular approach to renal denervation and providing patients, with resistant hypertension, with a new therapeutic option that is minimally invasive and can be performed rapidly under local anaesthesia. With this method the afferent and efferent sympathetic nervous fibers surrounding the renal artery are ablated precisely keeping the renal artery intact. To date, this technique has been evaluated only in open-label trials including small numbers of highly selected resistant hypertensive patients with suitable renal artery anatomy. The available evidence suggests a significant and persistent blood pressure-lowering effect and a very low incidence of short & long term complications with no deleterious effects on renal function. These data, although promising, need confirmation in larger randomized controlled clinical trials with longerterm follow-up.DOI: http://dx.doi.org/10.3329/birdem.v2i2.12325(Birdem Med J 2012; 2(2): 104-112)

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Abstract 641: Renal Denervation does not Lower Blood Pressure in Spontaneously Hypertensive Rats Treated with a Beta-1 Adrenergic Receptor Antagonist.

Hypertension ◽

10.1161/hyp.64.suppl_1.641 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Jeremiah Phelps ◽

Gregory Fink

Keyword(s):

Blood Pressure ◽

Adrenergic Receptor ◽

Renal Denervation ◽

Blood Pressure Response ◽

Beta Blockers ◽

Antihypertensive Drug Therapy ◽

Spontaneously Hypertensive ◽

Adrenergic Antagonist ◽

Before And After ◽

Pre Treatment

We have used the SHR as an animal model to understand how renal denervation (RDN) lowers blood pressure. In order to determine how concomitant antihypertensive drug therapy could affect the blood pressure response to RDN, we performed RDN both before and after chronic (several days) treatment via the drinking water with the selective alpha-1 adrenergic antagonist prazosin and the selective beta-1 adrenergic antagonist atenolol. In the presence of prazosin treatment, RDN (n=7) significantly (p<0.05) lowered mean arterial pressure (MAP) compared to sham operated (SO; n=6) SHR (Δ=–4.0±1.7mmHg in RDN-SHR vs +1.5±1.3 in SO-SHR). Subsequent addition of atenolol during prazosin treatment reduced MAP significantly in both groups, but MAP in SO-SHR fell to the same level as in RDN-SHR, i.e. the antihypertensive effect of RDN was lost. After discontinuation of all drug treatment, the change in MAP from pre-treatment baseline was –7.7±3.5mmHg in RDN-SHR and +3.0±4.0mmHg in SO-SHR, p=0.06). To test whether the BP response to RDN would be lost during blockade of beta-1 adrenergic receptors alone, we performed RDN in SHR (n=5) pre-treated with atenolol. Atenolol alone significantly reduced MAP (Δ=-20.7±2.5mmHg). Steady-state MAP was not further reduced by RDN (Δ=+2.1±0.9mmHg). When atenolol was withdrawn MAP rose but remained reduced from baseline (Δ= -9.5±0.9mmHg). This magnitude of BP reduction is comparable to what we have previously observed after RDN in untreated SHR. In summary, in SHR RDN does not lower BP in the presence of an effective antihypertensive dose of a beta-1 antagonist. This indicates that RDN is reducing BP in SHR by interrupting a mechanism also affected by beta-1 adrenergic receptor signaling. Although further investigation is necessary, the data suggest that possibility that patients on clinically effective antihypertensive doses of beta-blockers may not exhibit a good response to RDN.

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