RDB Jaquiss Duke University Is “Four Stage Management” the Future of Univentricular Hearts? – Destination Therapy in the Young RDB Jaquiss Duke University

Disclosures None

Current Paradigm for Palliation Stage I – shunt/band PROTECT PVR Stage II – superior CPC RELIEVE VOLUME LOAD Stage III – Fontan completion RELIEVE CYANOSIS If (when?) palliation fails - transplant

Normal  (A) The normal cardiovascular circulation. The pulmonary circulation (P) is connected in series with the systemic circulation (S). The right ventricle maintains the right atrial pressure lower than the left atrial pressure, and provides enough energy to the blood to pass the pulmonary resistance. (B) The patient with a univentricular heart. The systemic and pulmonary circuits are connected in parallel, with a considerable volume overload to the single ventricle (V). The width of the line reflects the degree of volume load. There is complete admixture of systemic and pulmonary venous blood, causing arterial oxygen desaturation. (C) The Fontan circulation. The systemic and pulmonary circulations are connected in series. The right atrium (RA) or systemic veins are connected to the pulmonary artery (PA). The volume overload to the single ventricle is now less than expected for body surface area. In the absence of fenestration, there is no more admixture of systemic and pulmonary venous blood, but the systemic venous pressure is notably elevated. Ao; aorta; LA, left atrium; LV, left ventricle, RV, right ventricle.

Single Ventricle  (A) The normal cardiovascular circulation. The pulmonary circulation (P) is connected in series with the systemic circulation (S). The right ventricle maintains the right atrial pressure lower than the left atrial pressure, and provides enough energy to the blood to pass the pulmonary resistance. (B) The patient with a univentricular heart. The systemic and pulmonary circuits are connected in parallel, with a considerable volume overload to the single ventricle (V). The width of the line reflects the degree of volume load. There is complete admixture of systemic and pulmonary venous blood, causing arterial oxygen desaturation. (C) The Fontan circulation. The systemic and pulmonary circulations are connected in series. The right atrium (RA) or systemic veins are connected to the pulmonary artery (PA). The volume overload to the single ventricle is now less than expected for body surface area. In the absence of fenestration, there is no more admixture of systemic and pulmonary venous blood, but the systemic venous pressure is notably elevated. Ao; aorta; LA, left atrium; LV, left ventricle, RV, right ventricle.

Fontan Circulation  (A) The normal cardiovascular circulation. The pulmonary circulation (P) is connected in series with the systemic circulation (S). The right ventricle maintains the right atrial pressure lower than the left atrial pressure, and provides enough energy to the blood to pass the pulmonary resistance. (B) The patient with a univentricular heart. The systemic and pulmonary circuits are connected in parallel, with a considerable volume overload to the single ventricle (V). The width of the line reflects the degree of volume load. There is complete admixture of systemic and pulmonary venous blood, causing arterial oxygen desaturation. (C) The Fontan circulation. The systemic and pulmonary circulations are connected in series. The right atrium (RA) or systemic veins are connected to the pulmonary artery (PA). The volume overload to the single ventricle is now less than expected for body surface area. In the absence of fenestration, there is no more admixture of systemic and pulmonary venous blood, but the systemic venous pressure is notably elevated. Ao; aorta; LA, left atrium; LV, left ventricle, RV, right ventricle.

Fontan Circulation  (A) The normal cardiovascular circulation. The pulmonary circulation (P) is connected in series with the systemic circulation (S). The right ventricle maintains the right atrial pressure lower than the left atrial pressure, and provides enough energy to the blood to pass the pulmonary resistance. (B) The patient with a univentricular heart. The systemic and pulmonary circuits are connected in parallel, with a considerable volume overload to the single ventricle (V). The width of the line reflects the degree of volume load. There is complete admixture of systemic and pulmonary venous blood, causing arterial oxygen desaturation. (C) The Fontan circulation. The systemic and pulmonary circulations are connected in series. The right atrium (RA) or systemic veins are connected to the pulmonary artery (PA). The volume overload to the single ventricle is now less than expected for body surface area. In the absence of fenestration, there is no more admixture of systemic and pulmonary venous blood, but the systemic venous pressure is notably elevated. Ao; aorta; LA, left atrium; LV, left ventricle, RV, right ventricle.

How Well and How Long Does It Work? Conditional Freedom from Death or Transplant 5 years 94% 10 years 90% 15 years 87% 20 years 83%

A Very Large and Excellent Experience Conditional Survival Atriopulmonary 25 years 76% Lateral Tunnel 20 years 90% Extracardiac 13 years 97% 2

A Closer Look Survival Isn’t Everything

Problems with Fontan Circulation Low Cardiac Output (70% of Normal at Rest) Impaired Exercise Capacity pre-load (PVR) determined Thromboembolism Arrythmias Hepatopathy Nephropathy Death

Developments in Fontan Surgery Description by Fontan and Baudet Ten Commandments Lateral Tunnel Extracardiac Staging Fenestration Fontan conversion Intra/Extra “Y” Grafts

(A) The normal cardiovascular circulation  (A) The normal cardiovascular circulation. The pulmonary circulation (P) is connected in series with the systemic circulation (S). The right ventricle maintains the right atrial pressure lower than the left atrial pressure, and provides enough energy to the blood to pass the pulmonary resistance. (B) The patient with a univentricular heart. The systemic and pulmonary circuits are connected in parallel, with a considerable volume overload to the single ventricle (V). The width of the line reflects the degree of volume load. There is complete admixture of systemic and pulmonary venous blood, causing arterial oxygen desaturation. (C) The Fontan circulation. The systemic and pulmonary circulations are connected in series. The right atrium (RA) or systemic veins are connected to the pulmonary artery (PA). The volume overload to the single ventricle is now less than expected for body surface area. In the absence of fenestration, there is no more admixture of systemic and pulmonary venous blood, but the systemic venous pressure is notably elevated. Ao; aorta; LA, left atrium; LV, left ventricle, RV, right ventricle. Marc Gewillig Heart 2005;91:839-846

“…pattern of endothelial dysfunction-induced remodeling due to chronic, non-pulsatile flow with in situ thrombotic lesions.”

Fontan Circulation  (A) The normal cardiovascular circulation. The pulmonary circulation (P) is connected in series with the systemic circulation (S). The right ventricle maintains the right atrial pressure lower than the left atrial pressure, and provides enough energy to the blood to pass the pulmonary resistance. (B) The patient with a univentricular heart. The systemic and pulmonary circuits are connected in parallel, with a considerable volume overload to the single ventricle (V). The width of the line reflects the degree of volume load. There is complete admixture of systemic and pulmonary venous blood, causing arterial oxygen desaturation. (C) The Fontan circulation. The systemic and pulmonary circulations are connected in series. The right atrium (RA) or systemic veins are connected to the pulmonary artery (PA). The volume overload to the single ventricle is now less than expected for body surface area. In the absence of fenestration, there is no more admixture of systemic and pulmonary venous blood, but the systemic venous pressure is notably elevated. Ao; aorta; LA, left atrium; LV, left ventricle, RV, right ventricle.

Modes of Fontan Failure Pump failure (LV<RV) Intrinsic, iatrogenic, arrythmic, valvular Concept failure “high”PVR leading to high Fontan pressure PLE, plastic bronchitis Cyanosis (V-V collaterals)

Scope of Problem STS Congenital Database 7/2010 to 6/2014 3245 “Fontan” operation (excluding conversions) 810/year entering pipeline Scientific Registry of Transplant Recipients

Total Heart Transplants – U.S.

47% of patients were listed as Status 2 (i.e. high PVR failure) Status 2 – 10% waitlist mortality Status 1 (inotropes) – 40% waitlist mortality Status 1 (ventilator) – 70% waitlist mortality

Changing Profile of Adult Heart Transplant 2002 and 2012 % Urgency Status 1A 660 34.8 1190 58.5 1B 723 38.2 743 36.5 2 509 26.9 102 5.0 Bridge No VAD 1454 76.8 1194 58.7 VAD 440 23.2 841 41.3

Application of LVAD Pump failure (LV<RV) Concept failure Intrinsic, iatrogenic, arrythmic, valvular Concept failure “high”PVR leading to high Fontan pressure PLE, plastic bronchitis Cyanosis (V-V collaterals)

“As many as two thirds of adult Fontan patients who die or require transplantation do so with preserved ventricular function.”

LVAD for Concept Failure – “Pulling”

Concept Failure – “Pushing” “Fontan patients are doomed to a circulatory failure and many of them will require a circulatory assistance as a bridge to transplantation.”

RVAD vs. LVAD Pushing vs. Pulling Power Requirements X 0.25 X Size Small Smaller Embolic Consequences Very Bad Bad Duarbility Unknown Unknown+++

Fig. 2 Aortic flow and superior vena cava (SVC) pressure at various phases of the experiment (mean flow and pressure of all 4 animals). Aortic flow decreased with institution of the Fontan circulation and was restored upon activation of the VAD. SVC pressu...

Factors Which Will Impact Future

Right Heart Failure after LVAD ~10-15% temporary RVAD ~20-30% moderate RVF Worse survival DT Worse outcome BTT Worse QOL

“It's tough to make predictions, especially about the future.” Yogi Berra

Transplant vs. Fontan-RVAD Resting Cardiac Output Normal Exercise Cardiac Output Hepatic Venous Pressure Normal to Slightly Elevated Chronic Anticoagulation No Yes Power Cord Probably Immunosuppression Risks Diabetes, Hypertension, Renal Failure Additional Surgery Needed Yes (Redo Tx) Yes (Redo VAD or Tx)

Future Paradigm for Palliation Stage I – shunt/band PROTECT PVR Stage II – superior CPC RELIEVE VOLUME LOAD Stage III – Fontan completion RELIEVE CYANOSIS SET UP STAGE IV Stage IV A. Pump Failure leads to transplant B. Concept Failure leads to RVAD (timing?)