To perform a percutaneous renal sympathetic denervation in a cohort of 20 patients with therapy resistant CPVT and LQTS patients and to objectify and evaluate the benefit of this novel treatment for this group of patients.
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint in this study will be cardiac events after renal denervation,
defined as:
(1) an appropriate ICD shock, defined as an ICD shock on ventricular
fibrillation or ventricular tachycardia
(2) arrhythmic syncope, seizures, or aborted cardiac arrest(3) number of ventricular extra systoles (VES) in CPVT patients
(3) malignant non-sustained VT (NSVT)
Secondary outcome
n.a.
Background summary
Primary inherited arrhythmia syndromes, such as long QT syndrome (LQTS) and
catecholaminergic polymorphic ventricular tachycardia (CPVT), are genetic
cardiac diseases without apparent structural heart disease that may cause
cardiac syncope and sudden cardiac death in mainly young individuals. These
cardiac events are mainly induced by physical- or emotional stress, i.e.
adrenergic, triggers. Hence, *-blockers are considered first line therapy in
symptomatic and asymptomatic patients in both conditions.In addition, an
implantable cardiac defibrillator (ICD) is often used in patients who continue
to have ventricular arrhythmias despite *-blocker therapy.5, 6 However, ICDs do
not prevent ventricular arrhythmias and can even trigger catecholamine release,
subsequently resulting in arrhythmic storms and even death.7 Also the cost of
frequent shocks in terms of pain and fear is substantial8 and young patients
with ICDs are more likely to experience device complications over many years of
use, including inappropriate shocks and lead-related complications9.
In 1971 Moss and McDonald10 described left cardiac sympathetic denervation
(LCSD), which prevents norepinephrine release in the heart and therefore
raising the threshold for ventricular fibrillation without reducing the heart
rate or impairing myocardial contractility.11 In the last decade LCSD received
renewed attention as a viable alternative treatment for therapy resistant LQTS
and CPVT patients. Although a significant protective effect of LCSD was
demonstrated in both symptomatic and asymptomatic LQTS and CPVT patients12-16,
arrhythmias do not completely resolve in a significant proportion of the
patients. Therefore, an additional therapy would be expedient wherein further
attenuation of sympathetic drive is performed.
Catheter-based radiofrequency ablation of the renal sympathetic nerves is a
novel minimally invasive procedure which lowers blood pressure in patients with
resistant hypertension.17-20 This procedure was tested in the Symplicity-HTN-2
trial of 106 patients with resistant hypertension despite treatment with an
average of five antihypertensive medications including a diuretic.18 The
patients were randomly assigned to renal sympathetic denervation or maintenance
of previous medical therapy. At six months, radiofrequency ablation
significantly decreased the office blood pressure from 178/97 to 143/85 mmHg
compared with no decrease in blood pressure in patients maintained on baseline
antihypertensive therapy. In addition, a systolic pressure of less than 140
mmHg was attained significantly more often with radiofrequency ablation (39
versus 6 percent). There was no significant difference between the groups in
kidney function and no serious adverse events were reported.
With the therapeutic effects of LCSD in mind, the sympathicolytical effect of
catheter-based percutaneous renal denervation might further promote a
reduction in cardiac arrhythmic events in LQTS and CPVT patients. Preliminary,
unpublished, data from a reliable CPVT mouse model provide very promising
results. The same mouse model, i.e. the CASQ2 homozygous knockout, was used to
demonstrate the efficacy of flecainide, (Watanabe et al. NatMed 2009) a therapy
that is now widely used in patients in whom B-blockade provide not sufficient
protection (van der Werf 2011). Renal Denervation (RDN) seem to provide full
protection in this model for the exercise-induced arrhythmias, whereas, as one
would expect, isoproterenol-induced arrhythmias are unaffected. These observed
positive experimental data bare the hope that this innovative technique might
extend the currently very limited armory against this group of patients and its
hereforementioned substantial risks.
Study objective
To perform a percutaneous renal sympathetic denervation in a cohort of 20
patients with therapy resistant CPVT and LQTS patients and to objectify and
evaluate the benefit of this novel treatment for this group of patients.
Study design
Single-armed clinical intervention cohort study.
Intervention
Patients will be treated by renal sympathetic nerve denervation using RF energy
applied with a balloon catheter. The
treatment takes 30-60 seconds (depending on the length of the renal artery) and
will be applied in both renal arteries
Study burden and risks
With any interventional procedure, there are possible risks and complications.
It is believed that the risks associated with
the use of the V2 Catheter are similar to other angioplasty devices.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Inclusion Criteria
1. Subjects who have provided written informed consent;
2. Subjects who are * 18 years of age;
3. Subjects who in the last year have had at least 1 event related to therapy refractory CPVT or LQTS
4. Subjects with a eGFR * 45 ml/min per 1.73m2;
5. Subjects who are willing and able to comply with all study procedures. ;Anatomical Inclusion Criteria
1. Subjects with or without an accessory renal artery who have a main renal artery diameter of * 3.5 mm and * 7.0 mm for each of their kidneys
2. Subjects who have a main renal artery without significant stenosis (defined as < 30%)
3. Subjects who have a renal artery length of * 15 mm.
Exclusion criteria
1. Subjects who are contraindicated for intravascular contrast material;
2. Subjects who are contraindicated for anticoagulation medications (heparin, aspirin, Angiomax, etc.), analgesic medications (morphine, fentanyl, etc.), anxiolytic medications (alprazolam, lorazepam, diazepam, etc.) or other medications required for an interventional procedure;
3. Subjects with known bleeding or hyper-coagulation disorders;
4. Subjects who have type 1 diabetes mellitus;
5. Subjects who have experienced a myocardial infarction, unstable angina pectoris, uncompensated heart failure, or a cerebrovascular accident within six (6) months prior to the screening visit, or have widespread atherosclerosis, with documented intravascular thrombosis or unstable plaques;
6. Subjects who have planned percutaneous vascular or surgical intervention for any reason within the next six (6) months;
7. Subjects who have hemodynamically significant valvular heart disease for which reduction of blood pressure would be considered hazardous;
8. Subjects who have any serious medical condition, which in the opinion of the investigator, may adversely affect patient safety or the efficacy of the procedure in the study (i.e., patients with clinically significant peripheral vascular disease, abdominal aortic aneurysm, bleeding disorders);
9. Female participants of childbearing potential must have a negative serum or urine human chorionic gonadotropin (hCG) pregnancy test prior to the procedure;
10. Subjects who have a known, unresolved history of drug use or alcohol abuse/dependency;
11. Subjects who are currently enrolled in any investigational study wherein patient participation has not been completed;
12. Subjects who, for any reason, may not be able to understand or comply with instructions. ;Anatomical Exclusion Criteria
1. Subjects with only one kidney;
2. Subjects with prior renal denervation procedure;
3. Subjects with prior intervention to right or left renal artery;
4. Subjects with renal artery stenosis as defined by * 30% stenosis confirmed by angiography with two (2) orthogonal views with selective catheterization;
5. Subjects with iliac stenosis requiring intervention at time of procedure and/or within the next six (6) months;
6. Subjects with severe femoral, renal, iliac or aortic calcification that may cause a potential complication at the time of the procedure;
7. Subjects in which the physician is unable to cannulate the renal artery;
8. Subjects in which the physician is unable to access the femoral artery by percutaneous means.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL47656.018.14 |