Thoratec Corporation HEARTMATE 3™ LEFT VENTRICULAR ASSIST SYSTEM

Implantation Procedure Using Surgical Techniques Other Than Full Median Sternotomy Addendum to the HeartMate 3™ Instructions for Use

Addendum to the HeartMate 3 Left Ventricular Assist System Instructions for Use ii Addendum to the HeartMate 3 Left Ventricular Assist System Instructions for Use United States & Canada Thoratec Corporation (International Headquarters) 6035 Stoneridge Drive Pleasanton, CA 94588 USA Telephone: (925) 847-8600 Fax: (925) 847-8574

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©2019 Thoratec Corporation. Document: 100167359.A Publication Date: 10/2019

Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use iii iv Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use Contents

Addendum to the HeartMate 3™ Instructions for Use ------vii Implantation Procedure Using Surgical Techniques Other Than Full Median Sternotomy ------vii Additional HeartMate 3 Accessories ------vii

HeartMate 3™ Implantation Procedure Using Surgical Techniques Other Than Full Median Sternotomy ------1-1 Cardio-Pulmonary Bypass (CPB) ------1-2 LVAD Implantation Steps ------1-3

Clinical experience with Implantation of HeartMate 3™ by Lateral Thoracotomy ------2-1 Background ------2-1 Results ------2-1 Conclusions ------2-3 References ------2-4

Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use v Contents

vi Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use Addendum to the HeartMate 3™ Instructions for Use

Implantation Procedure Using Surgical Techniques Other Than Full Median Sternotomy

This addendum contains a description of an implantation procedure that does not require a full median sternotomy and is intended to supplement the HeartMate 3™ Left Ventricular Assist System Instructions for Use. In particular, these instructions are meant to provide an alternative to the full median sternotomy implantation procedure as described in Chapter 5, “Surgical Procedures”, of the HeartMate 3™ Left Ventricular Assist System Instructions for Use.

Additional HeartMate 3 Accessories

In addition to the HeartMate 3 Implant Kit, this procedure may use the following accessories: • Mini Apical Cuff. For more information, refer to the HeartMate 3™ Mini Apical Cuff Kit Instructions for Use. • Apical Cuff Holder. For more information, refer to the HeartMate 3™ Mini Apical Cuff Kit Instructions for Use. • Coring Tool. For more information, refer to the HeartMate 3™ Coring Tool Instructions for Use.

Addendum to the HeartMate 3 Left Ventricular Assist System Instructions for Use vii

viii Addendum to the HeartMate 3 Left Ventricular Assist System Instructions for Use 1 HeartMate 3™ Implantation Procedure Using Surgical Techniques Other Than Full Median Sternotomy This document is intended to augment the HeartMate 3 Instructions for Use in order to provide an implantation method of the HeartMate 3 Left Ventricular Assist Device (LVAD) that does not require a full median sternotomy. WARNING ! • Thoroughly review all Warnings and Cautions found in Chapter 5 of the HeartMate 3 Instructions for Use regarding device preparation and implantation. • Do not attempt to use the Coring Tool in ventricles with wall thickness greater than 21mm. Use of the Coring Tool in tissue greater than 21mm may result in inadequately cored tissue and challenges removing the Coring Tool from the ventricle. • If any anatomical or technical complications present, use the standard sternotomy surgical approach as described in Chapter 5 of the HeartMate 3 Instructions for Use instead of the surgical approach described in this Addendum.

CAUTION ! • Please review the section, Clinical experience with Implantation of HeartMate 3™ by Lateral Thoracotomy, on page 2-1of this Addendum before deciding on the best surgical approach for the implantation of the HeartMate 3 LVAD. • When sewing the Apical Cuff or Mini Apical Cuff to the exterior of the heart, the felt surface should have a flat or convex shape. This is so that the pump and Slide Lock mechanism can engage the metal ring on the Mini Apical Cuff or Apical Cuff. • When sewing the Apical Cuff or Mini Apical Cuff to the exterior of the heart, the sutures should not create protrusions of the myocardial tissue that would prevent the LVAD from fully approximating a flat/convex Mini Apical Cuff or Apical Cuff. • The suture knots should not interfere with the connection. • If a sealing agent is used on or near the Apical Cuff or Mini Apical Cuff, it should not interfere with the Slide Lock mechanism. • If the Slide Lock mechanism on the HeartMate 3 LVAD fails to engage, do not make further attempts to engage until retracting the Slide Lock mechanism. Evidence of the Slide Lock mechanism failing to engage will be either visual evidence of the yellow “wings,” or a tactile feel of three ridges versus one. The Slide Lock will not engage the Apical Cuff or Mini Apical Cuff unless initially fully retracted. • If difficulty persists when engaging the Slide Lock mechanism, the LVAD should be removed from the Apical Cuff or Mini Apical Cuff to visualize what might be preventing the connection.

Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use 1-1 1

CAUTION ! • The Mini Apical Cuff must be affixed to the Left Ventricle only by the Sew-Then-Cut method. Using the Cut-Then-Sew method may lead to challenges with engaging the Slide Lock mechanism.

• The Mini Apical Cuff must be affixed to the Left Ventricle only by the prescribed technique in this document to avoid challenges with engaging the Slide Lock mechanism.

• Sharp instruments enter the left ventricle during this procedure. Guide all sharp instruments with caution.

• Avoid counter-clockwise rotation or oscillation of Coring Tool while cutting as tissue may be released into the ventricle.

• Avoid rotating the center rod within the blade while cutting tissue as this can result in tissue twisting or release of cored tissue.

• Always retract the helix into the Coring Tool before engaging the blade into the tissue. The helix may damage the septum if the blade cores the tissue before retracting the helix.

• Depressing the locking tabs may cause the helix to retract with force. Maintain a grip on the locking tabs while deflecting.

• Once the helix is retracted into the Coring Tool, the surgeon should avoid re-engaging the center rod to the blade until the Coring Tool is removed from the ventricle as tissue may be released into the ventricle.

• Components of the system that are supplied sterile are intended for single use only and should not be reused or re-sterilized. Do not use sterile components if sterile packaging is compromised. Contact Abbott for a Return Authorization number.

1-2 Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use 1

Cardio-Pulmonary Bypass (CPB)

The implant procedure should be performed while the patient is supported on cardio-pulmonary bypass. The following cannulation options may be used based upon surgeon preference: • Central cannulation, • Peripheral cannulation, or • Combination of central and peripheral.

LVAD Implantation Steps 1. Create access/exposure to the ascending aorta.

2. Assess the location of the LV apex using a transthoracic echocardiogram (TTE). Create access/exposure of the left ventricular apex by performing a left anterolateral thora- cotomy preferably through the 4th, 5th, or 6th intercostal space based on the TTE find- ings.

3. Using echocardiography (2D or 3D – preferred), target desired Inflow Cannula coring site (and Apical Cuff position).

4. On the back table, attach the HeartMate 3 Outflow Graft to the HeartMate 3 pump cover.

Note: For information about attaching the HeartMate 3 Outflow Graft to the HeartMate 3 Pump, refer to the section titled, "Attaching the Sealed Outflow Graft to the Pump", in Chapter 5, “Surgical Considerations”, of the HeartMate 3™ Left Ventric- ular Assist System Instructions for Use.

Note: If using the HeartMate 3 Apical Cuff or the HeartMate Coring Knife, refer to Chapter 5 of the HeartMate 3 Instructions for Use.

5. Using the Mini Apical Cuff, Apical Cuff Holder and Coring Tool begin the Apical anastomosis. 6. Preparing the Mini Apical Cuff and Apical Cuff Holder: a. Engage the Cuff Holder to the Mini Apical Cuff by inserting the bottom part of the Cuff Holder into the metal ring of the Mini Apical Cuff. Notes: • One side of the Mini Apical Cuff is printed and should be facing the handle. The blank side of the Cuff goes onto the heart.

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• A silicone o-ring is present in the groove in the bottom part of the Cuff Holder and some resistance may be felt during insertion. b. Visually confirm that the Cuff Holder is fully seated in the metal ring of the Mini Apical Cuff. c. Confirm that the Apical Cuff Holder Tool’s luer cap is fully tightened to avoid unintentional blood loss from the tool. d. Place the assembly in a sterile area until it is time to suture the Mini Apical Cuff on the heart. 7. Securing Mini Apical Cuff to Ventricle a. Choose the LVAD cannulation site. Identify the LVAD cannulation site slightly ante- rior to the apex, a few centimeters lateral to the left anterior descending coronary artery. b. With the Mini Apical Cuff loaded on the Cuff Holder, mark the outer diameter of the Mini Apical Cuff on the left ventricle. c. Approximately 1 cm from the edge of where the felt will sit on the myocardium, place 2-0 pledgeted braided sutures. d. Apply corresponding suture to the felt ring of the Mini Apical Cuff to achieve a horizontal mattress suture, targeting their placement on or inside the black circumferential line marked on the Mini Apical Cuff felt. e. Place a minimum of four horizontal mattress sutures around the periphery of the Mini Apical Cuff. It is recommended that the four sutures be placed at the locations of the four radial black markings on the felt. f. Separate the sutures. Tie the sutures tightly, with 6 to 7 throws on each knot. g. Disconnect the Apical Cuff Holder from the Mini Apical Cuff by gently pulling on the Apical Cuff Holder.

Note: Hold on to the Mini Apical Cuff when detaching the Apical Cuff Holder to avoid applying the disengagement force to the sutured connection to the heart.

h. Secure a running suture around the periphery of the felt ring using a 3-0 monofila- ment suture, with the suture placed close to the felt. Target placement on or inside the circumferential black line marked on the felt ring.

i. Ensure that the bites of the running sutures are sufficiently close to each other to achieve hemostasis.

1-4 Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use 1

Note: This will help ensure that a hemostatic connection between the Mini Apical Cuff and the heart tissue, for which uninterrupted opposition between the myocardial tissue and the Mini Apical Cuff felt is required.

j. Inspect the area to ensure that the Mini Apical Cuff and surrounding tissue produces no interference that would prevent the LVAD from approximating the Mini Apical Cuff. k. Inspect the ventricular chamber for mural thrombi and crossing trabeculae, addressing both as needed. 8. Core the left ventricle with the Coring Tool. a. Align and insert the guide pin of the HeartMate 3 Coring Tool into the center of the HeartMate 3 Apical Cuff or HeartMate 3 Mini Apical Cuff. b. Align the orientation of the Coring Tool towards the mitral valve. c. Advance the Coring Tool guide pin through the myocardium until the helix is touching the ventricular surface. d. Turn the Coring Tool handle clockwise for three turns to install the helix into the tissue. e. Pinch the locking tabs on the back of the Coring Tool to retract the helix and pull the tissue to the blade. f. Turn the Coring Tool clockwise to core the ventricle. Continue rotating until the white line on the green center rod becomes visible and the ventricle is completely cored. Loss of rotation resistance is another indication that the coring is completed.

Note: The blade should rotate about the stationary helix.

g. Pull to remove Coring Tool from the heart. h. If resistance is felt while removing the Coring Tool from the ventricle then the tissue may not be fully cored. i. Pull back the locking tabs until the white line becomes visible while rotating the Coring Tool blade clockwise to cut the remaining tissue. j. Always rotate the blade about the stable helix. k. Inspect the ventricular chamber for mural thrombi and crossing trabeculae, addressing both as needed.

Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use 1-5 1

9. Confirming Hemostasis with the Apical Cuff Holder a. After coring the implant site, complete the following steps to check the hemostasis of the anastomosis of the Mini Apical Cuff. b. Push the Apical Cuff Holder onto the Mini Apical Cuff to re-engage to the Apical Cuff Holder. Ensure that the luer cap is tightened to the Apical Cuff Holder port. c. Fill the left ventricle with blood by increasing volume going to the heart and reduce that going to the CPB machine. d. Remove the luer cap to allow air in the ventricle to escape from the luer port on top of the Apical Cuff Holder. e. Once the ventricle is cleared of air and some bleed through is observed, close the luer port completely to prevent further bleeding. f. Check the anastomosis for bleeding. If any bleeding is observed, place additional sutures until bleeding is sufficiently addressed. g. Once hemostasis is verified, re-initiate cardiopulmonary bypass. h. Disconnect the handle by gently pulling on the Cuff Holder. 10. The following steps are required. Complete them in order of preference: • Insert pump into ventricle, orient the driveline and Outflow Graft, then lock the Cuff Lock into place per instructions in Chapter 5 of the HeartMate 3 Instructions for Use. • Tunnel the Outflow Graft with Bend Relief to the ascending aorta, taking care not to twist or kink the graft. • Anastomose the outflow graft to the ascending aorta per Chapter 5 of the HeartMate 3 Instructions for Use. Continue to remove air from the LVAD blood path. Initiate HeartMate 3 function and wean from cardiopulmonary bypass. • Connect Outflow Graft Bend Relief. Verify its locked position per Chapter 5 of the HeartMate 3 Instructions for Use. • Tunnel driveline as described in Chapter 5 of the HeartMate 3 Instructions for Use using preferred exit site location & exit method (silicone-to-skin or velour-to-skin). Place chest tubes per standard techniques and preference for drainage. 11. De-air and operate the pump per Chapter 5 of the HeartMate 3 Instructions for Use. 12. Close incisions per standard technique. 13. Continue with the remainder of the HeartMate 3 LVAD implant as instructed in Chapter 5 of the HeartMate 3 Instructions for Use.

1-6 Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use 2 Clinical experience with Implantation of HeartMate 3™ by Lateral Thoracotomy

Background

The Lateral Thoracotomy (LAT) implantation technique has been adopted as an alternate technique for the HeartMate 3 (HM3) LVAD (1 - 7). In the LAT approach (also called Less Invasive Surgery; LIS) the HM3 LVAD is implanted through a LAT incision, and a separate upper hemi-sternotomy or upper right mini-thoracotomy is performed to anastomose the outflow graft (3, 5, 6). LAT clinical experience with the HM3 LVAD has been collected in the HM3 ELEVATE (“Evaluating the HeartMate 3 with Full MagLev Technology in a Post-Market Approval Setting”) Registry and in the separate LAT Feasibility Study. ELEVATE, is a multi-center, voluntary, observational registry collecting post-marketing data of the HM3 LVAD. This Registry involves early post-marketing HM3 experience at predominantly European sites. The LAT Feasibility study was a single arm, prospective, multicenter study conducted in Europe.

Results

The ELEVATE Registry included 463 consented subjects with de novo implants who were enrolled between March 2015 and February 2017 at 25 European and 1 Asian centers. Of these 463 patients, 44 (9.5%) were implanted via LAT. The LAT Feasibility Study enrolled 13 consented patients at 3 European centers between May and December 2015. Both the ELEVATE Registry and the LAT Feasibility Study data presented below had a follow-up period of 180 days. Demographic data for ELEVATE Registry patients (divided by implant technique LAT and Sternotomy) and LAT Feasibility Study patients are presented below (Table 1.1). Overall median age was ~60 years and patients were predominantly male (85-90%). Bridge-to-Transplant was the main indication (approximately 65%). Most patients were in INTERMACS profile 2 to 4.

Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use 2-1 1

Table 1.1 Demographics ELEVATE Registry LAT Feasibility LAT group Sternotomy group Study (n=44) (n=419) (n=13) Median age years (range) 58 (36 - 76) 58 (16 - 77) 62 (42 – 70) % Male 91% 89% 85% Ischemic Etiology 45% (20/44) 49% (204/419) 23% (3/13) Indication: BTT 68% (30/44) 66% (275/419) 62% (8/13) DT 27% (12/44) 26% (110/419) 38% (5/13) Other 5% (2/44) § 8% (34/419) ? 0% (0/13) INTERMACS Profile: 1 11% (5/44) 9% (38/412) 0% (0/13) 2 20% (9/44) 23% (93/412) 0% (0/13) 3 43% (19/44) 38% (157/412) 77% (10/13) 4 25% (11/44) 28% (114/412) 23% (3/13) 5-6 0% (0/44) 2% (10/412) 0% (0/13) not provided 0 7 0 NYHA Class: I 0% (0/43) 0% (0/395) 0% (0/13) II 0% (0/43) 0% (0/395) 0% (0/13) IIIA 7% (3/43) 10% (39/395) 0% (0/13) IIIB 30% (13/43) 38% (152/395) 54% (7/13) IV 63% (27/43) 52% (204/395) 46% (6/13) not provided 1 24 0

The survival rates (% ± standard error) at 180 days observed in the three analysis cohorts are: 84.1% ± 5.5% for the ELEVATE LAT group, 92.3% ± 1.3% for ELEVATE Sternotomy group and 76.9% ± 11.7% for the LAT Feasibility Study. Table 1.2 presents the mortality and adverse events rates that occurred through 180 days of support in the three analysis cohorts. A total of 39 deaths occurred within 180 days in the ELEVATE Registry, of which 7 were in the LAT group and 32 were in the Sternotomy group. The causes of death of the 7 ELEVATE LAT patients were mostly non-cardiac (6 out of 7 including sepsis, multi-organ failure due to ischemic intestine, retroperitoneal bleeding and RV failure) and occurred primarily after the first 30 post-operative days (4 out of 7). In the LAT Feasibility Study, 3 patients out of 13 died prior to 180 days of non-cardiac causes (multi-organ failure from sepsis, hypotonus and vasoplegia, cranial trauma after a fall).

2-2 Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use 2

Table 1.2 Mortality and Adverse Events at 180 days ELEVATE Registry LAT Feasibility LAT group Sternotomy group Study (n=44) (n=419) (n=13) Mortality 7 (16% ± 5%) 32 (8% ± 1%) 3 (23% ± 12%) Bleeding 12 (27% ± 7%) 16 107 (26% ± 2%) 165 6 (46% ± 14%) 8 Bleeding requiring surgery 3 (7% ± 4%) 4 46 (11% ± 2%) 57 0 (0%) 0 GI Bleeding 2 (5% ± 3%) 2 24 (6% ± 1%) 31 2 (15% ± 10%) 2 Arrhythmias 3 (7% ±4%) 3 72 (17% ± 2%) 83 6 (46% ± 14%) 8 Pericardial Fluid 1 (2% ± 2%) 1 34 (8% ± 1%) 39 0 (0%) 0 Hypertension 1 (2% ± 2%) 1 10 (2% ± 1%) 11 2 (15% ± 10%) 2 Infection 15 (34% ± 7%) 23 149 (36% ± 2%) 220 3 (23% ± 12%) 5 Localized non-device 6 (14% ± 5%) 6 93 (22% ± 2%) 126 2 (15% ± 10%)) 3 infection Sepsis 5 (11% ± 5%) 6 39 (9% ± 1%) 42 1 (8% ± 7%) 1 Driveline 7 (16% ± 6%) 8 42 (10% ± 1%) 46 1 (8% ± 7%) 1 Ischemic Stroke 2 (5% ± 3%) 2 16 (4% ± 1%) 16 1 (8% ± 7%) 1 Hemorrhagic Stroke 2 (5% ± 3%) 2 5 (1% ± 1%) 5 0 (0%) 0 Other neurological dysfunction? 4 (9% ± 4%) 4 18 (4% ± 1%) 20 2 (15% ± 10%) 2 Psychiatric episode 0 (0%) 0 16 (4% ± 1%) 16 0 (0%) 0 Renal dysfunction 6 (14% ± 5%) 6 51 (12% ± 2%) 57 4 (31% ± 13%) 4 Respiratory Failure 5 (11% ± 5%) 5 71 (17% ± 2%) 79 0 (0%) 0 Right Heart Failure 9 (20% ± 6%) 9 55 (13% ± 2%) 55 0 (0%) 0 Required only Inotropes 5 (11% ± 5%) 5 24 (6% ± 1%) 24 0 (0%) 0 RVAD 3 (7% ± 4%) 3 29 (7% ± 1%) 29 0 (0%]) 0 Hemolysis 1 (2% ± 2%) 1 1 (<1% ± <1%) 1 1 (8% ± 7%) 1 Pump Thrombosis 0 (0%) 0 1 (<1% ± <1%) 1 0 (0%) 0 Wound Dehiscence 1 (2% ± 2%) 2 10 (2% ± 1%) 10 0 (0%) 0 124 (30% ± 2%) Other events 19 (43% ± 7%) 27* 7 (54% ± 14%) 11? 185§

Conclusions

The ELEVATE Registry and LAT Feasibility study provide initial information on the results of the HM3 when implanted via the LAT. The data may be useful to surgeons considering risks and benefits of LVAD implantation techniques. For additional HM3 experience, please refer to the HeartMate 3 Instructions for Use, Appendix A-1 to A-28, Summary of the Clinical Study, for the study results of the MOMENTUM 3 Clinical Trial.

Addendum to HeartMate 3 Left Ventricular Assist System Instructions for Use 2-3 1

References

1. Kocabeyoglu SS, Kervan U, Sert DE, Unal EU, Demirkan B, Guray Y, et al. Is it Possible to Implant HeartMate 3 Less Invasively? New Pump, New Approach. Artificial organs. 2018;42(12):1132-8. 2. Netuka I. HeartMate 3 left ventricular assist system implantation technique: the devil is in the detail. Interactive cardiovascular and thoracic surgery. 2018;27(6):946-9. 3. Potapov EV, Kukucka M, Falk V, Krabatsch T. Off-pump implantation of the HeartMate 3 left ventricular assist device through a bilateral thoracotomy approach. The Journal of thoracic and cardiovascular surgery. 2017;153(1):104-5. 4. Riebandt J, Wiedemann D, Simon P, Dimitrov K, Laufer G, Zimpfer D. Use of the Novel Surgical Enhancement Tools for Less Invasive Abbott HeartMate 3 Implantation. The Annals of thoracic surgery. 2018;106(4):e209-e10. 5. Schmitto JD, Krabatsch T, Damme L, Netuka I. Less invasive HeartMate 3 left ventricular assist device implantation. Journal of thoracic disease. 2018;10(Suppl 15):S1692-S5. 6. Wood KL, Ayers BC, Sagebin F, Vidula H, Thomas S, Alexis JD, et al. Complete Sternal-Sparing HeartMate 3 Implantation: A Case Series of 10 Consecutive Patients. The Annals of thoracic surgery. 2019;107(4):1160-5. 7. Wood KL, Ayers BC, Vidula H, Alexis JD, Barrus B, Prasad S, et al., editors. INTERMACS 3 and 4 Patients Have Excellent Outcomes after Complete Sternal-Sparing HeartMate 3 Implantation. Journal of Heart and Lung Transplantation; 2019.

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Thoratec Corporation 6035 Stoneridge Drive Pleasanton, CA 94588 Tel: 925-847-8600 Toll Free: 800-528-2577 Fax: 925-847-8574 www.thoratec.com. © 2019 Thoratec Corporation. Thoratec, the Thoratec logo, and HeartMate and HeartMate 3 are registered trademarks of Thoratec Corporation.