Neurostimulation of Spinal Nerves That Affect the Heart
Neurostimulation of Spinal Nerves That Affect the Heart
The purpose of this study is to study the use of neurostimulation in chronic advanced
 refractory heart failure.

 The study is determine if it is safe to use neurostimulation in patients with chronic
 advanced refractory heart failure and to also determine initial observations with regards to
 its potential effect on heart function and quality of life. The investigators hypothesis is
 that this study will show both safe and positive effect of neurostimulation on heart failure
 patients.
Protocol Summary

 Title EVALUATION OF THE SAFETY OF NEUROSTIMULATION IN PATIENTS WITH SYMPTOMATIC HEART FAILURE
 FEASIBILTIY STUDY

 Description A feasibility trial of the use of neurostimulation in chronic advanced refractory
 heart failure.

 Objective To determine the safety of neurostimulation in patients with chronic advanced
 refractory heart failure and to generate initial observations with regards to its potential
 effect on ventricular function and quality of life.

 Design The trial will be a randomized double blind crossover feasibility trial with 2 week
 and 1,2,3,4,5,6,7 month clinical follow-up.

 After device implantation, patients enrolled in the trial will have been randomly assigned to
 have device programmed to deliver impulses, active, or to have the device programmed not to
 deliver impulses, inactive, for 3 months.

 After the 3 month initial phase, the devices will be inactivated and a 4 week washout period
 will convene.

 At the end of washout period, patients that were inactive during initial phase will crossover
 to active and similarly patients that were active during initial phase will crossover to
 inactive.

 Patient Population Patients with non-ischemic or ischemic cardiomyopathy with a length of
 illness of at least 6 months who have met the inclusion and exclusion criteria.

 Enrollment Enrollment of a total of 10 intent-to-treat patients Investigational Sites Up to 2
 investigational sites in the US Data Collection Data collection will be obtained in three
 categories: markers of cardiovascular safety, markers of device-device interactions and
 markers of efficacy.
Inclusion

 1. Male or female ≥18 years;

 2. Chronic heart failure NYHA class III-IV of ischemic and non-ischemic etiology;

 3. Screening Left ventricular Ejection Fraction (LVEF) ≤ 30% measured at baseline by
 echocardiography;

 4. Screening 6 minute walk test score of less than 450 meters measured at baseline;

 5. Hospitalization for heart failure or outpatient IV administration of inotropic agents,
 human B-natriuretic peptide or IV diuretics within the past 12 months (stable for at
 least 2 weeks);

 6. On standard optimal medical therapy for CHF before medical therapy.*

 7. No changes in active cardiac medications during the 1 week prior to treatment;

 8. Written informed consent.

 -  Patients with current or prior symptoms of heart failure and reduced LVEF should
 be on stable optimally uptitrated medical therapy recommended according to
 current guidelines (Circulation. 2005; 112 (12): e154) as standard of care for
 heart failure therapy in the United States. This minimally includes an
 ACE-inhibitor (ACE-I) at stable doses for 1 month prior to enrollment, if
 tolerated, and a beta blocker (carvedilol, metoprolol succinate, or bisoprolol)
 for 3 months prior to enrollment, if tolerated, with a stable up-titrated dose
 for 1 month prior to enrollment. This also includes an Angiotensin II Receptor
 Blocker (ARB) at stable doses for 1 month prior to enrollment, if tolerated, when
 ACE-I is not tolerated. Stable is defined as no more than a 100% increase or a
 50% decrease in dose. If the patient is intolerant to ACE-I, ARB, or beta
 blockers, documented evidence must be available. In those intolerant to both
 ACE-I and ARB, combination therapy with hydralazine and oral nitrate should be
 considered. Therapeutic equivalence for ACE-I substitutions is allowed within the
 enrollment stability timelines. Aldosterone inhibitor therapy should be added
 when NYHA Class III or IV symptoms occur on standard therapy. If aldosterone
 inhibitor therapy is administered in Class II patients, it must be initiated and
 optimized prior to enrollment. Eplerenone requires dosage stability for 1 month
 prior to enrollment. Diuretics may be used as necessary to keep the patient
 euvolemic.

 Exclusion

 1. Inability to comply with the conditions of the protocol;

 2. Inability to perform cardiopulmonary exercise test due to mechanical physical
 limitations

 3. Presence of a transplanted tissue or organ or LVAD (or the expectation of the same
 within the next 12 months);

 4. Planned AICD or CRT within the next 12 months unless AICD is prescribed for primary
 prevention

 5. Pacemaker dependent patients.

 6. Acute MI, CABG, PTCA, within the past 3 months

 7. Chronic refractory angina or peripheral vascular pain;

 8. Valvular heart disease requiring repair or replacement;

 9. Need for chronic intermittent inotropic therapy;

 10. Malignancy: evidence of disease within the previous 5 years;

 11. Known HIV infection or immunodeficiency state;

 12. Chronic active viral infection (such as hepatitis B or C);

 13. Severe systemic infection: defined as patients undergoing treatment with antibiotics;

 14. Active myocarditis or early postpartum cardiomyopathy (within the first 6-months of
 delivery);

 15. Systemic corticosteroids, cytostatics and immunosuppressive drug therapy
 (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), DNA depleting or
 cytotoxic drugs taken within 4 weeks prior to study treatment;

 16. Patient is pregnant, of childbearing potential and not using adequate contraceptive
 methods, or nursing.;

 17. Patient scheduled for hospice care;

 18. Any other medical, social or geographical factor, which would make it unlikely that
 the patient will comply with study procedures (eg. Alcohol abuse, lack of permanent
 residence, severe depression, disorientation, distant location and a history of
 non-compliance).