INCOR Unique Periodic Flow Change Algorithm Promoting Native Aortic Valve Function During INCOR Therapy Patrycja Ganslmeier MD (Universitätsklinikum Klinik für Herz- und Gefäßchirurgie Regensburg, Germany) Prof. Christof Schmid MD (Universitätsklinikum Klinik für Herz- und Gefäßchirurgie Regensburg, Germany) Attilio Iacovoni MD (Azienda Ospedaliera Papa Giovanni XXIII Bergamo, Italy)
Aortic Valve Insufficiency in LVAD Therapy Continuous flow LVADs without Periodic Flow Change algorithm induce aortic valve insufficiency 1 π Development of aortic valve insufficiency (AI) 1 (mild to moderate) up to 52% during continuous flow (CF) LVAD support reported (no preoperative AI) 2 π Development of de novo AI during LVAD therapy is critical 4 and associated with: Exertion limitation Pulmonary congestion despite LVAD support Compromised net forward flow Possible surgical reintervention π Mortality doubled in patients with AI on continuous flow LVAD support (39% vs. 18%) 2 π Two potential mechanisms described that promote AI development: Aortic valve commissural fusion leads to valve fibrosis and degeneration² Aortic root dilatation with concomitant changes in wall elasticity and 3 chronically high diastolic aortic pressures π Independent risk factor for onset of AI: permanently closed aortic valve 2,3 2 1 Letsou et al., Is native aortic valve commissural fusion in patients with long-term left ventricular assist devices associated with clinically important aortic insufficiency?, J Heart Lung Transplant. 2006 Apr;25(4):395-9 2 Aggarwal et al., The development of aortic insufficiency in continuous-flow left ventricular assist device-supported patients, Ann Thorac Surg. 2013 Feb;95(2):493-8 3 Cowger et al., The development of aortic insufficiency in left ventricular assist devicesupported patients, Circ Heart Fail. 2010 Nov;3(6):668-74 4 Park, Aortic Insufficiency in LVAD Patients, oral communication ASAIO 59 th Annual Conference Chicago 2013 5 Iacovoni, Influence of Long Term INCOR therapy on aortic valve function, oral communication DGTHG 42 nd Annual Conference Freiburg 2013 6 Connelly et al., Acquired commissural fusion of aortic valves in patients with left ventricular assist devices, J Heart Lung Transplant. 2003 Dec;22(12):1291-5 7 John et al., Aortic valve pathophysiology during left ventricular assist device support, J Heart Lung Transplant. 2010 Dec;29(12):1321-9
Prevention of AI during LVAD therapy Acquired commissural fusion of aortic valves in patients on CF-LVAD support π Speed settings adjustment 4,5,7 π Blood pressure control 4,5 π Continuous echocardiography monitoring (M-mode interrogation of the aortic valve) FIGURE 1 Acquired commissural fusion of aortic valves in patients on CF-LVAD support (Adapted from Connelly, J Heart Lung Transplant. 2003 Dec;22(12):1291-5) Closed valves are prone to fusion and degeneration from lack of mobility in the setting of concomitant valve stress mediated by high pressure and velocity blood flow. 3 π Observing exercise tolerance and patients individual findings π INCOR Periodic Flow Change (PFC) algorithm 5 3 Freedom Aortic Valve from Insufficiency Primary Endpoint LVAD Therapy
INCOR Periodic Flow Change (PFC) Algorithm Operating principle of the INCOR PFC algorithm Speed Interval Set speed Duration of reduction Speed reduction Slew time Rise time Time FIGURE 2 Operating principle of the INCOR PFC algorithm The speed is reduced at fixed time intervals. After a defined period of speed reduction, the set speed is reinstated. Berlin Heart GmbH 4
Aortic valve function during LVAD support FIGURE 3A LVAD support without PFC during systole If the aortic valve is closed, the blood is ejected only through the LVAD. Berlin Heart GmbH FIGURE 3B LVAD support with PFC during systole The PFC algorithm induces the opening of the aortic valve. Berlin Heart GmbH 5 INCOR Periodic Flow Change (PFC) Algorithm
Influence of INCOR PFC Algorithm on Aortic Valve Function π Study type: Retrospective, multicenter* data analysis π Study objective: Influence of INCOR PFC algorithm on aortic valve function π Patient population: 16 patients (09/2008-01/2012) Follow-up at 6 month: 16 patients Follow-up at 12 month: 12 patients Pre-LVAD AI: 69% π *Trial sites: Universitätsklinikum Klinik für Herz- und Gefäßchirurgie Regensburg, Germany Azienda Ospedaliera Papa Giovanni XXIII Bergamo, Italy 6
Pressure difference [mmhg] Speed [rpm] Detection of aortic valve opening by analyzing pressure difference characteristic Pressure difference Flow rate 120 6.0 100 5.0 80 4.0 60 3.0 40 1.0 20 0.0 0-1.0-2.0 0 2.79 5.58 Time [s] 0 2.79 5.58 10000 Speed 8000 6000 4000 2000 Flow rate (l/min) Aortic valve closed Aortic valve open FIGURE 4 Detection of aortic valve opening by analyzing pressure difference characteristic Data of an INCOR patient was analyzed who presented aortic valve opening only during PFC algorithm. The speed characteristic displays the PFC algorithm. Opening of the aortic valve can be monitored by analyzing the pressure difference curve. Aortic valve open: If the aortic valve opens during systole, an instant pressure drop in the left ventricle is seen. The pressure difference curve increased displaying the rapidly increasing pressure difference between the aorta and the left ventricle. After the aortic valve is closed, the pressure difference curve follows the primary characteristic. Aortic valve closed: If the aortic valve is closed, the pressure difference curve displays the pressure increase and decrease in the left ventricle. Blood is pumped only through the INCOR system. Berlin Heart GmbH 7 Influence of INCOR PFC Algorithm on Aortic Valve Function
Patient characteristics Demographic data Primary cardiac diagnosis INTERMACS level Characteristics Value Mean age [years] (range) 49.6 (19-68) Mean weight [kg] (range) 75.0 (60-103) Mean BMI [kg/m 2 ] (range) 24.3 (20.6-33.3) Mean BSA [m 2 ] (range) 1.9 (1.7-2.3) Gender All male Other 19% Ischemic cardiomyopathy 12% Dilative cardiomyopathy 69% INTERMACS level 3 25% INTERMACS level 1 6% INTERMACS level 2 69% FIGURE 5 Primary cardiac diagnosis FIGURE 6 INTERMACS level 75% of the patients presented with INTERMACS level 1 or 2. 8
Results Overall outcome Percentage of patients 100 80 60 40 20 94% 69% 25% 6% 0 0 6 12 Time on device [month] FIGURE 7 Overall outcome 1-year survival was 94%, thereof 25% of the patients have been transplanted and 69% are still on support. Survival on system Transplanted Deceased Aortic valve insufficiency (AI) AI [Percentage of patients] 100 80 60 40 20 0 31% 69% 19% 81% 31% 69% 67% 25% pre-op at discharge 6 month 12 month FIGURE 8 Aortic valve insufficiency (AI) At 6 months on LVAD support, no AI was detected in 31% of the patients compared to 19% during check-up at discharge. At 12 months, 8% of the patients developed a moderate AI. No severe AI developed in any patient. Reduction of early onset of AI during INCOR support with PFC 0 (none) 1 (mild) 8% 2 (moderate) 3 (severe) 9 Influence of INCOR PFC Algorithm on Aortic Valve Function
Opening of the aortic valve Aortic valve free of fusion after INCOR therapy Opening of aortic valve [% of patients] 100 80 60 40 20 0 56% 50% 50% 42% 31% 25% 25% 13% 8% Echo at discharge Follow-up 6 months Follow-up 12 months FIGURE 9 Opening of the aortic valve Full opening of the aortic valve increased during LVAD support to 31% of the patients within the first 6 months and decreased slightly during the next 6 months to 42% of the patients. Full opening Intermittent opening Full closure FIGURE 10 Aortic valve free of fusion after INCOR therapy (by courtesy of Dr. A. Iacovoni) No aortic valve fusion was detected in the heart of an INCOR patient after transplantation (time on device 13 months). 10
Conclusion INCOR Periodic Flow Change (PFC) algorithm π promotes the opening of the aortic valve by modulating the speed at fixed intervals π reduces the early onset of AI during INCOR support, despite permanently closed aortic valve in 50% of the patients Detection of aortic valve opening by pressure difference trend analysis facilitates speed adjustment to further induce aortic valve opening. 11 Influence of INCOR PFC Algorithm on Aortic Valve Function
INCOR Periodic Flow Change (PFC) algorithm π promotes the opening of the aortic valve by modulating the speed at fixed intervals π reduces the early onset of AI during INCOR support, despite permanently closed aortic valve in 50% of the patients Berlin Heart GmbH Wiesenweg 10 12247 Berlin Germany Phone +49 30 81 87-26 00 Fax +49 30 81 87-26 01 info@berlinheart.de www.berlinheart.de Berlin Heart Inc. 200 Valleywood Road Suite B100 The Woodlands TX 77380 USA Phone +1 281 863-97 00 Fax +1 281 863-97 01 info@berlinheart.com www.berlinheart.com Version MFI21.0 September 2013 Berlin Heart GmbH