MITRACLIP CLIP DELIVERY SYSTEMS

INDICATION FOR USE

The MitraClip™ NTR/XTR System is indicated for the percutaneous reduction of significant symptomatic mitral regurgitation (MR ≥ 3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral regurgitation.

The MitraClip™ NTR/XTR System, when used with maximally tolerated guideline-directed medical therapy (GDMT), is indicated for the treatment of symptomatic, moderate-to-severe or severe secondary (or functional) mitral regurgitation (MR; MR ≥ Grade III  per American Society of Echocardiography criteria) in patients with a left ventricular ejection fraction (LVEF) ≥ 20% and ≤ 50%, and a left ventricular end systolic dimension (LVESD) ≤ 70 mm whose symptoms and MR severity persist despite maximally tolerated GDMT as determined by a multidisciplinary heart team experienced in the evaluation and treatment of heart failure and mitral valve disease.

CONTRAINDICATIONS

The MitraClip™ NTR/XTR System is contraindicated in patients with the following conditions:

Patients who cannot tolerate procedural anticoagulation or post procedural anti-platelet regimen

Active endocarditis of the mitral valve

Rheumatic mitral valve disease

Evidence of intracardiac, inferior vena cava (IVC) or femoral venous thrombus

WARNINGS

DO NOT use MitraClip™ outside of the labeled indication.

The MitraClip™ Implant should be implanted with sterile techniques using fluoroscopy and echocardiography (e.g., transesophageal [TEE] and transthoracic [TTE]) in a facility with on-site cardiac surgery and immediate access to a cardiac operating room.

Read all instructions carefully.  Failure to follow these instructions, warnings and precautions may lead to device damage, user injury or patient injury. Use universal precautions for biohazards and sharps while handling the MitraClip™ System to avoid user injury.

Use of the MitraClip™ should be restricted to those physicians trained to perform invasive endovascular and transseptal procedures and those trained in the proper use of the system.

The Clip Delivery System is provided sterile and designed for single use only.  Cleaning, re-sterilization and / or reuse may result in infections, malfunction of the device or other serious injury or death.

Use caution when treating patients with hemodynamic instability requiring inotropic support or mechanical heart assistance due to the increased risk of mortality in this patient population. The safety and effectiveness of MitraClip™ in these patients has not been evaluated.

PRECAUTIONS

Note the product “Use by” date specified on the package.

Inspect all product prior to use. Do not use if the package is open or damaged, or if product is damaged.

Prohibitive Risk Primary (or degenerative) Mitral Regurgitation

Prohibitive risk is determined by the clinical judgment of a heart team, including a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease, due to the presence of one or more of the following documented surgical risk factors:

30-day STS predicted operative mortality risk score of

≥8% for patients deemed likely to undergo mitral valve replacement or

≥6% for patients deemed likely to undergo mitral valve repair

Porcelain aorta or extensively calcified ascending aorta.

Frailty (assessed by in-person cardiac surgeon consultation).

Hostile chest

Severe liver disease / cirrhosis (MELD Score > 12)

Severe pulmonary hypertension (systolic pulmonary artery pressure > 2/3 systemic pressure)

Unusual extenuating circumstance, such as right ventricular dysfunction with severe tricuspid regurgitation, chemotherapy for malignancy, major bleeding diathesis, immobility, AIDS, severe dementia, high risk of aspiration, internal mammary artery (IMA) at high risk of injury, etc.

Evaluable data regarding safety or effectiveness is not available for prohibitive risk DMR patients with an LVEF < 20% or an LVESD > 60 mm.  MitraClipTM should be used only when criteria for clip suitability for DMR have been met.

The heart team should include a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease and may also include appropriate physicians to assess the adequacy of heart failure treatment and valvular anatomy.

Secondary Mitral Regurgitation

Evaluable data regarding safety or effectiveness is not available for secondary MR patients with an LVEF < 20% or an LVESD > 70 mm.

The multidisciplinary heart team should be experienced in the evaluation and treatment of heart failure and mitral valve disease and determine that symptoms and MR severity persist despite maximally tolerated GDMT.

POTENTIAL COMPLICATIONS AND ADVERSE EVENTS

The following ANTICIPATED EVENTS have been identified as possible complications of the MitraClipTM procedure.

Death; Allergic reaction (anesthetic, contrast, Heparin, nickel alloy, latex); Aneurysm or pseudo-aneurysm; Arrhythmias; Atrial fibrillation; Atrial septal defect requiring intervention; Arterio-venous fistula; Bleeding; Cardiac arrest; Cardiac perforation; Cardiac tamponade / Pericardial Effusion; Chordal entanglement / rupture; Coagulopathy; Conversion to standard valve surgery; Deep venous thrombus (DVT); Dislodgement of previously implanted devices; Dizziness; Drug reaction to anti-platelet / anticoagulation agents / contrast media; Dyskinesia; Dyspnea; Edema; Emboli (air, thrombus, MitraClipTM Implant); Emergency cardiac surgery; Endocarditis; Esophageal irritation; Esophageal perforation or stricture; Failure to deliver MitraClipTM to the intended site; Failure to retrieve MitraClipTM System components; Fever or hyperthermia; Gastrointestinal bleeding or infarct; Hematoma; Hemolysis; Hemorrhage requiring transfusion; Hypotension / hypertension; Infection; Injury to mitral valve complicating or preventing later surgical repair; Lymphatic complications; Mesenteric ischemia; MitraClipTM Implant erosion, migration or malposition; MitraClipTM Implant thrombosis; MitraClipTM System component(s) embolization; Mitral stenosis; Mitral valve injury; Multi-system organ failure; Myocardial infarction; Nausea / vomiting; Pain; Peripheral ischemia; Prolonged angina; Prolonged ventilation; Pulmonary congestion; Pulmonary thrombo-embolism; Renal insufficiency or failure; Respiratory failure / atelectasis / pneumonia; Septicemia; Shock, Anaphylactic or Cardiogenic; Single leaflet device attachment (SLDA); Skin injury or tissue changes due to exposure to ionizing radiation; Stroke or transient ischemic attack (TIA); Urinary tract infection; Vascular trauma, dissection or occlusion; Vessel spasm; Vessel perforation or laceration; Worsening heart failure; Worsening mitral regurgitation; Wound dehiscence

INDICATIONS AND USAGE

The AMPLATZERTM PFO Occluder is indicated for percutaneous transcatheter closure of a patent foramen ovale (PFO) to reduce the risk of recurrent ischemic stroke in patients, predominantly between

the ages of 18 and 60 years, who have had a cryptogenic stroke due to a presumed paradoxical embolism,

as determined by a neurologist and cardiologist following an evaluation to exclude known causes of ischemic stroke.

CONTRAINDICATIONS

• Patients with intra-cardiac mass, vegetation, tumor or thrombus at the intended site of implant, or documented evidence of venous thrombus in the vessels through which access to the PFO is gained.
• Patients whose vasculature, through which access to the PFO is gained, is inadequate to accommodate the appropriate sheath size.
• Patients with anatomy in which the AMPLATZERTM PFO device size required would interfere with other intracardiac or intravascular structures, such as valves or pulmonary veins.
• Patients with other source of right-to-left shunts, including an atrial septal defect and/or fenestrated septum.
• Patients with active endocarditis or other untreated infections.

WARNINGS

• Patients who are at increased risk for venous thromboembolic events should be managed with thromboembolic risk reduction regimen after the PFO Closure following standard of care.
• Do not use this device if the sterile package is open or damaged.
• Prepare for situations that require percutaneous or surgical removal of this device. This includes availability of a surgeon.
• Embolized devices must be removed as they may disrupt critical cardiac functions. Do not remove an embolized occluder through intracardiac structures unless the occluder is fully recaptured inside a catheter or sheath.
• Patients who are allergic to nickel can have an allergic reaction to this device.
• This device should be used only by physicians who are trained in standard transcatheter techniques.
• Transient hemodynamic compromise may be encountered during device placement, which may require fluid replacement or other medications as determined by the physician.
• Do not release the device from the delivery cable if the device does not conform to its original configuration, or if the device position is unstable or if the device interferes with any adjacent cardiac structure (such as Superior Vena Cava (SVC), Pulmonary Vein (PV), Mitral Valve (MV), Coronary Sinus (CS), aorta (AO)). If the device interferes with an adjacent cardiac structure, recapture the device and redeploy. If still unsatisfactory, recapture the device and either replace with a new device or refer the patient for alternative treatment.
• Ensure there is sufficient distance from the PFO to the aortic root or SVC (typically defined as 9 mm or greater as measured by echo). See Figure 6. and Figure 7.

PRECAUTIONS

• The safety and effectiveness of the AMPLATZERTM PFO Occluder has not been established in patients (with):
  • Age less than 18 years or greater than 60 years because enrollment in the pivotal study (the RESPECT trial) was limited to patients 18 to 60 years old
  • A hypercoagulable state including those with a positive test for a anticardiolipin antibody (IgG or IgM), Lupus anticoagulant, beta-2 glycoprotein-1 antibodies, or persistently elevated fasting plasma homocysteine despite medical therapy
  • Unable to take antiplatelet therapy
  • Atherosclerosis or other arteriopathy of the intracranial and extracranial vessels associated with a ≥50% luminal stenosis
  • Acute or recent (within 6 months) myocardial infarction or unstable angina
  • Left ventricular aneurysm or akinesis
  • Mitral valve stenosisorsevere mitral regurgitation irrespective of etiology
  • Aortic valve stenosis (mean gradient greater than 40 mmHg) or severe aortic valve regurgitation
  • Mitral or aortic valve vegetation or prosthesis n Aortic arch plaques protruding greater than 4 mm into the aortic lumen
  • Left ventricular dilated cardiomyopathy with left ventricular ejection fraction (LVEF) less than 35%
  • Chronic, persistent, or paroxysmal atrial fibrillation or atrial flutter
  • Uncontrolled hypertension or uncontrolled diabetes mellitus
  • Diagnosis of lacunar infarct probably due to intrinsic small vessel as qualifying stroke event
  • Arterial dissection as cause of stroke
  • Index stroke of poor outcome (modified Rankin score greater than 3)
  • Pregnancy at the time of implant n Multi-organ failure
• Use on or before the last day of the expiration month that is printed on the product packaging label.
• This device was sterilized with ethylene oxide and is for single use only. Do not reuse or re-sterilize this device. Attempts to re-sterilize this device can cause a malfunction, insufficient sterilization, or harm to the patient.
• The AMPLATZERTM PFO Occluder device consists of a nickel-titanium alloy, which is generally considered safe. However, in vitro testing has demonstrated that nickel is released from this device for a minimum of 60 days. Patients who are allergic to nickel may have an allergic reaction to this device, especially those with a history of metal allergies. Certain allergic reactions can be serious; patients should be instructed to notify their physicians immediately if they suspect they are experiencing an allergic reaction such as difficulty breathing or inflammation of the face or throat. Some patients may also develop an allergy to nickel if this device is implanted.
• Store in a dry place.
• Pregnancy – Minimize radiation exposure to the fetus and the mother.
• Nursing mothers – There has been no quantitative assessment for the presence of leachables in breast milk.

ADVERSE EVENTS

Potential adverse events that may occur during or after a procedure using this device may include, but are not limited to:

Air embolus Allergic drug reaction; Allergic dye reaction; Allergic metal reaction: Nitinol (nickel, titanium), platinum/iridium, stainless steel (chromium, iron, manganese, molybdenum, nickel); Anesthesia reactions; Apnea; Arrhythmia; Bacterial

endocarditis; Bleeding ; Brachial plexus injury; Cardiac perforation; Cardiac tamponade; Cardiac thrombus; Chest pain; Device embolization; Device erosion; Deep vein thrombosis; Death; Endocarditis; Esophagus injury; Fever; Headache/migraine; Hypertension/hypotension; Myocardial infarction; Pacemaker placement secondary to PFO device closure; Palpitations; Pericardial effusion; Pericardial tamponade; Pericarditis; Peripheral embolism; Pleural effusion; Pulmonary embolism; Reintervention for residual shunt/device removal; Sepsis; Stroke; Transient ischemic attack; Thrombus; Valvular regurgitation; Vascular access site injury;

Vessel perforation

INDICATIONS FOR USE

The SJM^TM Masters Series Mechanical Heart Valve is intended for use as a replacement valve in patients with a diseased, damaged, or malfunctioning mitral or aortic heart valve. This device

may also be used to replace a previously implanted mitral or aortic prosthetic heart valve.

The sizer model 905-15 is indicated to confirm size selection of the 15AHPJ-505 and 15MHPJ-505 valves.

CONTRAINDICATIONS

The SJM^TM Masters Series Mechanical Heart Valve is contraindicated for individuals unable to tolerate anticoagulation therapy.

The sizer model 905-15 is contraindicated for use with any devices other than the 15 AHPJ-505 and 15MHPJ-505 valves. Any sizer sterilization method other than steam is contraindicated.

WARNINGS

Valve

• For single use only. Attempts to reuse the valve may result in valve malfunction, inadequate sterilization, or patient harm.
• Use only St. Jude MedicalTM mechanical heart valve sizers.
• Do not use if:
  • The valve has been dropped, damaged, or mishandled in anyway.
  • The expiration date has elapsed.
  • The tamper-evident container seal or inner/ outer tray seals are damaged, broken, or missing.
• Remove any residual tissue that may impair valve size selection, correct seating of the valve, rotation of the valve, or leaflet motion.
• Proper valve size selection is crucial. Do not oversize the valve. If the native annulus measurement falls between two SJM^TM Masters Series Mechanical Heart Valve sizes, use the smaller prosthetic valve size.
• The outer tray is not sterile, and should not be placed in the sterile field.
• To minimize direct handling of the valve during implantation, do not remove the holder/rotator until the valve has been seated in the annulus.
• Do not use hard or rigid instruments to test leaflet mobility, as this may result in structural damage to the valve or thromboembolic complications. Use a St. Jude MedicalTM leaflet tester to gently test valve leaflet mobility.
• Place sutures in the outer half of the valve sewing cuff.
• Never apply force to the valve leaflets. Force may cause structural damage to the valve.
• Use only SJM^TM Valve Holder/Rotators to perform valve rotation. Use of other instruments could result in structural damage. The valve holder/rotator is intended for single use only and should be discarded after surgery.
• The two retention sutures on the valve holder/ rotator must be cut and removed before the valve can be rotated.
• Do not pass catheters or other instruments through St. Jude MedicalTM mechanical heart valves. This could result in scratched or damaged valve components, leaflet fracture, or dislodgment.
• Cut suture ends short, especially in the vicinity of the pivot guards, to prevent leaflet impingement.

PRECAUTIONS

Valve

• Do not touch the prosthetic valve unnecessarily, even with gloved hands. This may cause scratches or surface imperfections that may lead to thrombus formation.
• Be careful not to cut or tear the valve sewing cuff when removing the identification tag and the holder/rotator from the valve.
• Before placing sutures in the valve sewing cuff, verify that the valve is mounted correctly on the valve holder/rotator.
• To avoid structural damage, the valve must be rotated in the fully open position.
• To minimize rotational torque, verify that the valve holder/rotator is properly seated in the valve, and that the valve holder handle is perpendicular to the valve.
• Remove any loose suture or thread, which may be a source of thrombus or thromboembolism.
• Implantation of a prosthetic valve too large for the annulus may result in increased risk of damage to the conductive system, obstruction of the left ventricular outflow tract, impairment of valve mobility, damage to the left circumflex artery, and damage to surrounding tissues or cardiac structures including obstruction and/or distortion of adjacent cardiac structures.
• NOTE: PROSPECTIVE DATA TO SUPPORT SAFETY AND EFFECTIVENESS OF THE 15-mm HP VALVE IMPLANTED IN THE AORTIC POSITION ARE NOT CURRENTLY AVAILABLE.

Sizer

• Instruments must be cleaned and sterilized prior to use.
• Do not use cracked, deformed, discolored/rusted, or damaged instruments.
• Improper cleaning may result in an immunological or toxic reaction.
• Instrument sterilization temperature must not exceed 280°F (138°C).
• Do not bend flexible instrument handles beyond a 90° angle.
• Instruments must be sterilized in a tray or container that is permeable to steam.
• Do not expose instruments to cleaning or rinse agents that are not compatible with polysulfone or polyphenylsulfone.

POTENTIAL ADVERSE EVENTS

Complications associated with replacement mechanical heart valves include, but are not limited to, hemolysis, infections, thrombus, or thromboembolism, valve dehiscence, unacceptable hemodynamic performance, hemorrhagic complications secondary to anticoagulation therapy, heart block requiring pacemaker implant, prosthetic failure, adjacent cardiac structure interference, heart failure, stroke, myocardial infarction, or death. Any of these complications may require reoperation or explantation of the device.