CALM-DIEM_EUR - Controlling and Lowering Blood Pressure with the MobiusHD* - Defining Efficacy Markers ;CALM-DIEM_EUR Sub-study - Studying the Effect of the MobiusHDTM on Sympathetic Activity and Baroreflex Sensitivity;CALM-DIEM_HTN-HF Sub-study - Studying the Effect of the MobiusHD® System in Hypertensive Patients with mild Chronic Heart Failure

1. >= 18 years of age and <= 80 years of age;
2. Diagnosed with primary resistant hypertension;
3. Mean 24-hour systolic ABPM is >=130 mmHg following at least 30 days on a
stable anti-hypertensive medication regimen (no changes in medication or dose)
and no more than 7 days prior to implantation.For the sub-study:
1. Eligible for the CALM-DIEM Study and having passed all CALM-DIEM Study
inclusion and exclusion criteria at CALM-DIEM Study ScreeningFor the HF
sub-study:
1. Eligible for the CALM-DIEM Study and having passed all CALM-DIEM Study
inclusion and exclusion criteria at CALM-DIEM Study Screening
2. Mild to moderate chronic heart failure (New York Heart Association
(NYHA) Class II or III)ndefined

1. An inability provide written informed consent.
2. Known or clinically suspected baroreflex failure or autonomic neuropathy.
3. Known significant aortoiliac or common femoral artery disease that will
prohibit safe femoral access.
4. Hypertension secondary to an identifiable and treatable cause other than
sleep apnea (e.g., hyperaldosteronism, renal artery stenosis, pheochromocytoma,
Cushing's disease, co-arctation of the aorta, hyperparathyroidism and
intracranial tumor).
5. Treatable cause of resistant hypertension including, but not limited to,
improper BP measurement, volume overload and pseudotolerance (excessive sodium
intake, volume retention from kidney disease, inadequate diuretic therapy),
drug-induced or other causes (non-adherence, inadequate doses, inappropriate
combinations, NSAIDs, COX-2 inhibitors, cocaine, amphetamines, or other drugs,
sympathomimetics, oral contraceptives (confirmed cause of resistant
hypertension), adrenal steroids, cyclosporine, and tacrolimus, erythropoietin ,
licorice (including some chewing tobacco), ephedra, ma haung, bitter orange);
and excessive alcohol intake.
6. Arm circumference greater than 46 cm and/or BMI >= 45.
7. Chronic atrial fibrillation or recurrent atrial fibrillation with episode
within the last twelve (12) months.
8. History of bleeding complications with dual antiplatelet therapy in the past
or has known uncorrectable bleeding diathesis.
9. Current use of anticoagulation therapy, other than dual antiplatelet
medications. Examples include vitamin K antagonists and novel oral
anticoagulants including apixaban, rivaroxaban, dabigatran etexilate and
edoxoban.
10. Peptic ulcer disease with documented active ulcer or bleeding within the
last year.
11. History of allergy to contrast media that cannot be managed medically.
12. Persistent symptomatic orthostatic hypotension (>20/10 mmHg).
13. Persistent symptomatic syncope documented to be related to hypertension
within the last six (6) months.
14. History of myocardial infarction or unstable angina within the past three
(3) months.
15. History of cerebral vascular accident (stroke or TIA) within the past year,
and NIHSS >5 or mRs >1.
16. Chronic kidney disease (GFR calculated by the Modification of Diet in Renal
Disease equation < 45 ml/min).
17. Prior carotid surgery, radiation, or endovascular stent placement in either
carotid region.
18. Severe valvular or structural heart disease (excluding LV hypertrophy).
19. Severe chronic obstructive pulmonary disease (requiring twenty-four-hour
oxygen or oral steroids), asthma, or severe pulmonary hypertension.
20. Uncontrolled diabetes mellitus with HbA1c >= 10 %.
21. Active infection within the last month requiring antibiotics.
22. Uncontrolled co-morbid medical condition, including mental health issues,
that would adversely affect participation in the trial.
23. Co-morbid condition that reduces life expectancy to less than one (1) year.
24. Planned surgery or other procedure within the next six (6) months requiring
cessation of antiplatelet medications.
25. Pregnant or lactating females. For females of child-bearing potential, a
positive pregnancy test within seven (7) days of the pre-randomization
screening or refusal to use a medically accepted method of birth control for
the duration of the trial;
26. Presence of visible atherosclerotic plaque or areas of intimal thickness
(IMT) of >1500 micron in the region of the carotid bifurcation (15 mm proximal
and 15 mm distal to the ICA ostium), determined at a central core laboratory.
27. Significant obstructive vascular disease, calcification or plaque of aortic
arch and great vessels by ultrasound, CTA or MRA;
28. Renal artery stenosis >50% or systolic gradient >10mmHg in borderline cases
diagnosed by renal artery imaging in the last 36 months. Acceptable renal
artery imaging modalities include renal duplex, magnetic resonance angiography,
CT angiography, and selective or nonselective renal angiography depending on
trial site diagnostic standards;
29. Internal Carotid Artery (ICA) lumen diameters <5 mm or >12.5 mm within the
planned location of the implant placement via CTA or MRA. Evidence of landing
zone restrictions, such as inadequate length, vessel tapering, and/or vessel
curvature that would preclude safe placement of the implant;
30. Enrolled in a concurrent clinical trial or an investigational drug or
device that has not yet reached its primary endpoint.
31. Unable or unwilling to fulfill the protocol follow-up requirements.
32. Subject is a prisoner or member of other vulnerable population. For the
sub-study:
1. An inability to provide written informed consent for the sub-study;
2. Use of anti-hypertensive medications directly acting on the sympathetic
nervous system, that
cannot be discontinued safely;
3. Uncontrolled or involuntary movements disturbing microneurography, such as
tremors, fasciculations and chorea;
4. Absence or paralysis of both legs;
5. Polyneuropathy or clinical suspicion for autonomic nervous system
dysfunction;
6. Known claustrophobia;
7. Metallic implants, prostheses or other foreign bodies causing potential
artefacts obscuring the visibility of signals from the site of MobiusHD
implantation during MRI scanning;
8. Cochlear implants, pacemakers, neurostimulators, stents or grafts at risk of
malfunction due to the magnetic field;
9. Underlying conditions that prohibit a Valsalva maneuver: i.e. aortic
stenosis, cardiac arrhythmia, glaucoma, and/or retinopathy.Angiographic
1. Evidence of any carotid plaque, ulceration or any stenosis on selective
carotid angiography performed in orthogonal views. Luminal diameters will be
assessed to exclude subjects with ICA lumen diameters < 5 mm or > 11.75 mm
within the planned location of the device placement;
2. Any angiographic evidence of plaque or ulceration in the aortic arch and/or
the supra aortic vasculature;
3. Inappropriate anatomy of the carotid bifurcation for deployment of the
MobiusHD, including, but not limited to; tortuosity of the extracranial vessels
and significant angulation of the common carotid artery bifurcation;
4. Type III arch or horizontal takeoff of the left carotid from the innominate
and calcification of the carotid bulb.For the HF sub-study:
1. Patients must not have any of the following specific Heart Failure Sub-study
exclusion criteria:
• NYHA Class IV Heart Failure
• Acute pulmonary edema or unstable angina within 60 days
• On IV inotropic medication
• Receiving cardiac resynchronization therapy

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