Renal Denervation in the Treatment of Resistant Hypertension and Difficult-to-Control Hypertension – Consensus Document of the Croatian Hypertension League – Croatian Society of Hypertension, Croatian Cardiac Society, Croatian Endovascular Initiative, Croatian Society for Diabetes and Metabolic Diseases, Croatian Renal Association, and Croatian Society of Family Physicians of the Croatian Medical Association

Figures & data

Figure 1 Systolic blood pressure (ABPM) reduction and durability - results obtained in the of sham-controlled studies using new methods and from the Global Symplicity Registry.

Figure 2 Effect of renal denervation on: (A) systolic (blue) and diastolic (red) BP, and (B) heart rate after 6 months of follow-up. Data from the Croatian renal denervation registry.

Figure 3 The effect of renal denervation on the nocturnal pattern (systolic blood pressure (A1) and diastolic blood pressure (A2) and on the morning BP surge (B). Data from the Croatian renal denervation registry. Definition of morning BP surge: Sleep-trough morning BP surge is the difference between the mean systolic BP over 2 hours following the awakening and the average of three BP values centered on the lowest nocturnal BP.

Figure 4 Changes in estimated glomerular filtration rate (eGFR) and albuminuria (24-hour urine) during the six- month follow-up. Data from the Croatian renal denervation registry.

Table 1 Complications and Side Effects (%) in the Sham-Controlled Trials (Second Generation)

	Studies Spyral HTN-OFF, Spyral HTN-ON, Radiance-HTN SOLO, Radiance-HTN TRIO	Global Symplicity Registry
	N = 442	N= 3000
Hypertensive crisis/events	0.6	2.6
Stroke/TIA	0.4	3.2
CV death	0.2	2
Newly developed renal artery stenosis	0.2	0.1
Acute myocardial infarction	0.2
Femoral access site pseudoaneurysm	0.2
Increase in serum creatinine	0.2	1.5
End-stage-kidney disease		1.6

Box 1 Exclusion Criteria for Renal Denervation

Exclusion Criteria
1. White coat hypertension
2. Secondary hypertensions  – renovascular atherosclerotic hypertension  – primary aldosteronism  – hyperthyroidism  – hypothyroidism  – pheochromocytoma  – Morbus Cushing  – coarctation of the aorta
3. Pregnancy
4. Anatomically inadequate renal arteries

Box 2 Secondary Hypertension Where Renal Denervation Could Be Considered

Secondary Hypertension where RDN is Possible
1. Obesity
2 Chronic kidney disease* (including haemodialysis patients and kidney transplant patients with resistant AH)
3. Obstructive sleep apnea syndrome (OSA)
4. Primary aldosteronism**

Notes: *RDN to be done with CO_2, or exceptionally with low doses of contrast and then taking care to prevent contrast-induced nephropathy. **In patients in whom surgery is not possible or who is not prone to surgery.

Table 2 Groups of Patients in Whom Renal Denervation Could Be Considered by the Consensus of the Croatian Hypertension League

Group 1 Resistant Hypertension Treated with ACE-i-ARB/CCB/tD in the Optimal dose	Group 2 Uncontrolled Hypertension Treated With ≥ 2 Medicines In The Optimal Dose	Group 3 Special Groups of Patients
Side effects/intolerance of MRA	Side effects to antihypertensive drugs	Chronic kidney disease
Permanently poor adherence (despite education)	Permanently poor adherence (despite education)	Obstructive sleep apnea sy.
Uncontrolled AH	Uncontrolled AH	Atrial fibrillation
	Masked uncontrolled AH	Heart failure
	Non-dipping/rising pattern	Isolated systolic AH (elderly)
	Morning SBP surge (> 50 mmHg)
	Heart rate (24h) > 74/min
High/very high CV risk	High/very high CV risk	High/very high CV risk
	HFpEF
Shared decision making with the patient	Shared decision making with the patient	Shared decision making with the patient

Abbreviations: MRA, mineralocorticoid receptor antagonists; AH, arterial hypertension; SBP, systolic blood pressure; CV, cardiovascular; HFpEF, heart failure with preserve ejection function.

Table 3 Diagnostic Tests Before Renal Denervation

Mandatory Tests Before RDN
Blood group Rh factor
Red blood count
Coagulogram
eGFR
Serum potassium
Plasma renin activity, aldosterone
NT pro BNP
24h urine: sodium, potassium, albumin, creatinine
ABPM*
ECG
Office PWV (Sphygmocor)
Office central aortic pressure*
Additional tests before RDN
ABPM – central aortic pressure and central PWV
CAVI - determination of arterial stiffness independent of BP
ANX - determining the activity of the vegetative nervous system

Note: *Validated devices.

Abbreviations: RDN, renal denervation; eGFR, estimated glomerular filtration rate; ABPM, ambulatory blood pressure monitoring, PWV, pulse wave velocity; CAVI, cardio-ankle vascular index; ANX, sympathetic /parasympathetic activity): The ANSAR ANX 3.0 system.

Figure 5 Diagnostic and therapeutic algorithm for setting the indication for renal denervation according the consensus of the Croatian Hypertension League.

Table 4 Tests That Need to Be Done During Patient Follow-Up After Renal Denervation

	−1 Day	+1 Day	+1 Month	+3 Months	+6 Months	+12 Months	+18 Months	+24 Months
Office blood pressure and heart rate (sitting)	+	+	+	+	+	+	+	+
Office blood pressure and heart rate (standing)	+	+	+	+	+	+	+	+
Checking cooperation -medical history	+	+	+	+	+	+	+	+
Checking cooperation -Toxicol. Lab	+		+	+	+	+	+	+
Blood group Rh factor	+
Red blood cell count	+					+		+
Coagulogram	+
Serum creatinine (eGFR)	+		+	+	+	+		+
Plasma renin activity, Aldosterone	+					+		+
NT proBNP	+			+	+	+		+
Fasting blood glucose, insulin, HbA1C	+			+		+		+
Uric acid, lipids	+			+		+		+
24h urine: Na, K, albumin, creatinine	+		+		+	+	+	+
ABPM	+	+	+	+	+	+	+	+
ECG	+				+	+		+
PWV	+	+		+	+	+		+
CAP	+	+		+	+	+		+
CAVI	+	+		+	+	+		+
ANX	+	+	+	+	+	+		+
Color Doppler renal arteries					+			+
MRI / CO2 angiography						+

Abbreviations: eGFR, estimated glomerular filtration rate; ABPM, ambulatory blood pressure monitoring, PWV, pulse wave velocity; CAP, central aortic pressure; CAVI, cardio-ankle vascular index; ANX, sympathetic/ parasympathetic activity): The ANSAR ANX 3.0 system; MRI, magnetic resonance imaging.

Table 5 Areas of Scientific and Research Work in Renal Denervation in Croatia

1. Predictors of a Positive Response	2. Effects Beyond BP Lowering	3. Special Groups of Patients
– arterial stiffness (PWV measured in the office and 24h PWV, CAVI) – central aortic pressure (measured in the office and 24h CAP) – heart rate (measured in the office and using ABPM) – kidney function (eGFR) – salt intake (24-hour urine sodium excretion) –sympathetic/parasympathetic activity	– variability and circadian rhythm of BP – CAP –arterial stiffness (office, 24h PWV, CAVI) – sympathetic activity – kidney function (eGFR) – albuminuria (24.-hour urine) –metabolic effects (glycemia, insulin resistance, dyslipidemia, uric acid…)	– patients on a chronic dialysis program – kidney transplant patients – heart failure – atrial fibrillation – OSA – isolated systolic hypertension (in elderly and in youth) – patients with diabetes and a very high CV risk

Abbreviations: eGFR, estimated glomerular filtration rate; ABPM, ambulatory blood pressure monitoring, PWV, pulse wave velocity; CAP, central aortic pressure; CAVI, cardio-ankle vascular index; OSA, obstructive sleep apnea syndrome.