When and How to Replace an LVAD Nader Moazami, MD Department of Thoracic and Cardiovascular Surgery and Biomedical Engineering, Cleveland Clinic

Disclosures NONE

> 10,000 patients, 141 Hospitals Between June 23, 2006 and December 31, 2013, 158 hospitals participated in INTERMACS and, of these, 141 hospitals actively contributed information on a total of 10,542 primary implant patients. Cumulative patient accrual and the number of participating hospitals over this period are displayed. Kirklin et al J Heart Lung Transplant. 2014 Jun;33(6):555-64

Indications For LVAD Exchange Mechanical Pump Failure (rare if ever) Lead Failure (10-20%) “Other”: inflow cannula malposition; outflow graft kinking; “bend relief” disconnection (<10%) Infection (10%)

Infectious Complications

Hazard of Driveline infections Koval et al JHLT 2014 Nov;33(11):1164-72

LVAD infection and Transplantation Tong et al Ann Thorac Surg (in press)

Indications For LVAD Exchange Pump Thrombosis/Hemolysis (50-60%)

Free of Thrombosis at 3 Mo. 100 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 80 ● % ● 60 40 2006 2008 2010 2012 HeartMate II Implant Date

CONFIRMED Pump Thrombosis at 3 Months after HeartMate II Implantation 30 20 25 15 CC Duke 20 10 BJH Devices with Confirmed Pump Thrombosis (%) 15 5 Figure 1. Overall Occurrence of Confirmed Pump Thrombosis at 3 Months after HeartMate II Implantation. Dashed lines represent the 95% confidence interval. There was a steep increase in the occurrence of thrombosis starting in early 2011. The inset shows the changing occurrence of confirmed pump thrombosis according to study site (Cleveland Clinic [CC], Barnes–Jewish Hospital [BJH], and Duke University Medical Center [Duke]). 10 2004 2006 2008 2010 2012 2014 5 2004 2006 2008 2010 2012 2014 Implantation Year Starling RC et al. N Engl J Med 2013. DOI: 10.1056/NEJMoa1313385

Pump Thrombosis and Hemolysis

Clinical Presentation Conformed Pump Thrombosis (n=36) Parameters Number of Patients (% of N) Asymptomatic, no new symptoms 4 (11.1) Heart failure, new onset or worsening 20 (55.6) Renal dysfunction Chronic renal dysfunction Acute renal dysfunction 8 (22.2) 0 (0) Hematuria (N=30) 27 (90%) Thromboembolism 1 (2.8) Unexplained change in clinical status NYHA functional status Class I Class II Class III Class IV 2 (5.6) 12 (33.3) 17 (47.2) 5 (13.9)

Clinical Spectrum of HM2 Pump Thrombosis The clinical spectrum of VAD thrombosis. Patients with VAD thrombosis may be completely asymptomatic. The condition may progress, leading to a variable presentation, ranging from shortness of breath, low cardiac output state, valvular insufficiency, arrhythmias and right ventricular failure. With or without medical therapy, these patients can progress to cardiogenic shock and death. Despite the wide spectrum of presentations highlighted, there is a consistent finding of elevated LDH as a marker of active hemolysis in all patients. Edo et al JHLT 34, 613-615 (2015)

Months before Confirmed Pump Thrombosis Elevated Lactate Dehydrogenase (LDH) Levels within 3 Months after HeartMate II Implantation 2,500 2,000 BJH 1,500 LDH (IU\L) 1,000 Figure 3. Elevated Lactate Dehydrogenase (LDH) Levels within 3 Months after HeartMate II Implantation. The overall estimate of the percentage of patients with LDH levels of more than 1000 IU per liter within 3 months after the implantation of a HeartMate II is shown, without regard to diagnosis of confirmed or suspected pump thrombosis. The parametric estimate is shown (solid line) with the 95% confidence interval (dashed lines). The occurrence of elevated LDH levels increased steadily starting in 2011, which was similar to the pattern observed for pump thrombosis. The inset shows changes in occurrence according to study site. Duke 500 CC -3 -2 -1 Months before Confirmed Pump Thrombosis Starling RC et al. N Engl J Med 2013. DOI: 10.1056/NEJMoa1313385

Mortality According to Management Strategy after Confirmed Pump Thrombosis 70 60 Neither transplantation nor replacement 50 40 Patients Who Died (%) 30 Figure 5. Mortality According to Management Strategy after Confirmed Pump Thrombosis. Squares indicate deaths after heart transplantation or pump replacement, and diamonds indicate deaths of patients who did not undergo heart transplantation or pump replacement, with the horizontal axis truncated at 6 months. For reference, triangles indicate deaths without confirmed pump thrombosis during HeartMate II support from the time of implantation (gray). Symbols represent nonparametric estimates, and I bars 95% confidence intervals. The dashed line represents patients for whom follow-up data were available and who remained alive. Transplantation or replacement 20 10 HeartMate II support without thrombosis 1 2 3 4 5 6 Months Starling RC et al. N Engl J Med 2013. DOI: 10.1056/NEJMoa1313385

HVAD BTT Trial (n=382) Najjar, et al JHLT 33,;23-34 Kaplan-Meier analysis shows time to any thrombus event and time to left ventricular assist device exchange for pump thrombus. Najjar, et al JHLT 33,;23-34

HVAD DT Trial (ENDURANCE)

When to Change the Pump? Heartmate 2 LDH>2.5X monitor closely Superimposing Hemoglobinuria or any symptoms PUMP EXCHANGE HVAD Pump power elevavation: 1 or 2 rounds of tPA If no resolution PUMP EXCHANGE

Evaluation Prior To Pump Exchange TEE Contrast-enhanced CT Scan with 3-D reconstruction

3-D CT Imaging Mohamed I et al Radiographics. 2015 Mar-Apr;35(2):327-56

3-D CT Imaging Mohamed I et al Radiographics. 2015 Mar-Apr;35(2):327-56

Bend Relief Disconnect Mohamed I et al Radiographics. 2015 Mar-Apr;35(2):327-56.

Advantages of Non-Sternotomy Approach Less time on CPB Less Bleeding Shorter Ventilation Less RV Failure Shorter LOS

De-Airing

HVAD Exchange Left Anterolateral Thoracotomy Schmitto et al Artif Organs Vol 38;6, 2014 Sajjad et al EJCTS 43;1247-1250, 2012 Schmitto et al. J Thorac Cardiovasc Surg. 2012 Feb;143(2):511-3.

Conclusion Increasing number of exchanges for pump thrombosis With HM2 medical treatment likely futile and subcostal approach is preferred. With HVAD initial trial tPA seems warranted if unsuccessful them exchange through left anterolateral thoracotomy