1. Right Heart Failure in Left Ventricular Assist Device Recipients
Michael Kiernan, MD, MS
Assistant Professor of Medicine, Tufts University School of Medicine
Medical Director, Ventricular Assist Device Program, Tufts Medical Center

2. The problem with right heart failure following LVAD implantation
12 mo
78%
Total RVF 20%
6 % RVAD
7% early extended inotropes
7% late inotropes
Survival
(N=484)
59%
Historically RVAD 5-25%, RVF 20-40%
423 pts in BTT trial
RVF strong independent determinants of outcomes
Kormos. J Thorac Cardiovasc Surg 2010;39:1316

3. Identifying risk for RVF
Fukamachi1
Michigan RVFRS2
Kormos3
Device Type
Pulsatile
Pulsatile (84%) &
cf-LVAD (16%)
cf-LVAD
# of LVAD patients
100
197
484
RVF Definition
RVAD
RVAD, inotropes, iNO
RVAD, inotropes
Incidence of RVF
11%
35%
20%
Incidence RVAD
15% 6%
Institution
Single center
Multicenter
Predictors
Univariate
Multivariable
RVSWI < 300
Vasopressor support
Ventilator support
Mean PAP < 40
Bilirubin > 2.0 mg/dL
BUN > 39 mg/dL
AST
AST > 80 IU/L
RA/PCWP > 0.63
Creatinine > 2.3 mg/dL
Fukamachi: Cleveland Clinic: 64 Thoratec HM 1000 IP, 36, VE HM
Matthews: HMI IP pts, VE 65, XVE 77, HMII 28 (14%), micromed
Lack of consistently identified predictors of rvf across studies made identification of pts who would benefit from biventricular support difficult
Planned use of bivads improve clinical outcomes compared to delayed
Risk factors, multifactorial nature of RVF difficult to predict
Other risk factors: female gender, NICM
1. Fukamachi. Ann Thorac Surg 1999;68: Kormos. J Thorac Cardiovasc Surg 2010;139:1316
2. Mathews. J Am Coll Cardiol 2008;51:2163

4. Complex etiology of post-LVAD RV failure
RVD
High flow
Chronic
Intra-op ischemia
LVAD & IVS
RVF
RAP
PVR
CPB
PRBCs
Hypoxia
Acidosis
PRBCs TR
Hepatic/renal congestion
Many patients have some degree of preoperative right ventricular dysfunction then develop the syndrome of rv failure
Septum contributes > 1/3 systolic function of RV
Transfusion associated with pulmonary insufficiency. TRALI, complement activation with CPB
RH dysfunction worsening congestive hepatopathy, coagulopathy, bleeding
Historically overall RVF 10-40%, rvad 5-25%
Rv less susceptible to ischemic damage. Less myocardial mass and more favorable oxygen supply demand ratio
Excessive lvad flows may result in excessive rv preload
RV dilates and rv output is initially maintained at expense of elevated ra and RV end diastolic pressures
Maintain LVAD flows high enough to maintain end organ perfusion but low enough to avoid RV volume overload, adjust flows to minimize distortion of RV
Intraoperative RV protection
RV lower stroke work than LV, oxygen extraction 50 versus 75%
Coupled to highly compliant pulmonary vascular tree
Diagnosis is complex
Ventricular interdependence implies shape and size and compliance of one ventricle affect size shape and pressure volume relationship of other through direct mechanical interactions. Systolic inter-dependence is mediated primarily though IVS, while diastolic inter-dependence occurs mainly via pericardium
Successful filling of LVAD requires rv to increase output to match lvad flow
Global contractility of rv impaired during lvad support changes in ivs position and motion when lv unladed and ivs buldge into lv jeopardizing efficient rv contraction, rv free wall must work harder and cannot compensate for loss of septal function
Stroke Volume RV LV
McDonald. Curr Opin Card. 2009;24
Meineri. Best Pract & Res Clin Anesth (26):217
Pressure vessel (mmHg)

5. Severe RV Failure in INTERMACS
Continuous Flow LVAD
N =2900
RVAD at time of LVAD Implant
N = 84 (3%)
Return to OR for RVAD
N = 26 (1%)
4% of 2900 patients required RV support.
24% returned to OR, 76% in OR
9% durable
RVAD: Durable
N = 5 (6%)
RVAD: Temporary
N = 79 (94%)
RVAD: Durable
N = 5 (20%)
RVAD: Temporary
N = 21 (80%)
Kiernan. ISHLT 2012

6. 56% Cleveland. J Heart Lung Transplant 2011;30(8):862
Bivads have higher rates of infection, bleeding, 4-fold increase in neurologic complications
Cleveland. J Heart Lung Transplant 2011;30(8):862

7. Early management: Outcomes with planned versus delayed BiVAD
Survival until Discharge
P = 0.046
P = 0.001
P = 0.054
Median time to delayed RVAD 2 days
Mortality results primarily from MOSF, hemorrhage, thrombotic events, pulmonary complications
Need for RVAD most significant risk factor for LVAD recipients
ASAIO 2014: German experience. No difference in survival for thoratec bivad, HMII and r centrimag, LVAD with inotropes
Fitzpatrick (UPenn). J Thorac Cardiovasc Surg 2009;137(4):971

8. Risk Factors for Early RVAD Following LVAD Surgery
Adult Primary Continuous Flow Implants (N=2900)
Multivariable Logistic Regression (Event=RVAD)
Risk Factors (pre-implant) Odds Ratio p – value
INTERMACS Patient Profile Level <
PaPi (per 1 unit larger)
LVEDD (per 1 mm increase)
RV dysfunction by echo (any)
Primary Diagnosis CAD
Hemoglobin (per 1 gm/dl increase)
Concomitant surgery
INTERMACS Patient Profile Level
RVD by echo sensitive by not specific. If looks normal than probably okay, but dysfunction not helpful in determine need for bivad
Adjustment for multiple corrections with bon-fiori p < 0.001
Kiernan. ISHLT 2012

9. PA Systolic Pressure – PA Diastolic Pressure
Pulmonary Artery Pulsatility Index
PA Systolic Pressure – PA Diastolic Pressure
Right Atrial Pressure
PaPi =
Korabathina. Catheter Cardiovasc Interv Sep 27.

10. Prevention?: Pre-op optimization Class I (LOE C)
Therapy (Preload, Afterload, Inotropy):
Diuresis
Renal Replacement
Vasodilators
Inotropes
IABP/short term MCS
Vitamin K
Surgical technique
? RCA/LAD revascularization
Goals:
RA < 15 mmHg
Euvolemia
Correction metabolic derangements and end-organ function
Prevention?: Pre-op optimization
Class I (LOE C)
Two things to elicit RHF: decreased contractility or increased afterload
FS mechanism less important in RV hemodynamics
Larger surface to volume ratio: takes large increase in volume to stretch RV
RV more restrained by pericardium: increase fluid flattened septum
Recommended to admit preoperatively for tuning of RV
Patrick McCarthy’s at Cleveland clinicgroup demonstrated Vitamin K prevad 10mg sq daily for three days decreased post-operative nonsurgical (> 48 hrs) bleeding
Adequate BP necessary for coronary perfusion of RV
Piazza. Chest 2005;128:
ISHLT 2013 MCS Guidelines. JHLT 2013;32: 10

11. Implants June 2006 – March 2011: RHF Analysis
Adult Primary Continuous Flow Implants N=2900
By Right Heart Failure Level
Severe Right Heart Failure, n= 110
Moderate or Worse Right Heart Failure, n= 398
% Freedom RHF
Mild or Worse Right Heart Failure, n=1284
Overall p <
Event: Right Heart Failure
Months post implant

12. Readmission rate by cause following LVAD implantation
Hospitalization/(patient*yr)
Readmission rate
Hasin (Mayo). JACC 2013;61(2):153

13. Impact of Tricuspid Valve Repair at time of LVAD
LVAD Only
N=81
LVAD + TVR
N=34
P-value
Baseline Characteristics
SCr
0.32
BUN
0.06
CVP/PCWP *
<0.01
CVP
16 + 8
19 + 7
0.09
Severe TR
33%
62%
OUTCOMES
RVAD
10% 3%
0.27
Inotrope
10d (8,17)
8d (7,12)
0.04
Post-op renal insuff
39%
21%
0.05
Hosp LOS
23d (16,46)
19d (14,25)
0.02
LVAD + TVR
Survival
LVAD
Not consistent in some other cohorts.
Piacentino (Duke). Ann Thorac Surg 2011;92:1414

14. 2196 patients with mod-severe TR--27% TVR TVR associated with:
No difference in death or RVAD
Increased renal failure
Greater transfusion requirement
Increased LOS
Concomitant TVP did not affect risk post-operative right VAD insertion (risk ratio[RR],0.81;95%confidenceinterval [CI],0.49–1.36; p ¼ )or death(RR,0.95;95%CI,0.68–1.33; p ¼ ).
However, TVP was associated with increased risk post-operative renal failure(RR,1.53;95%CI,1.13–2.08; p ¼ ), dialysis(RR,1.49;95%CI,1.03–2.15; p ¼ ),
reoperation(RR,1.24;95%CI,1.07–1.45; p ¼ ),
Greater total transfusion requirement (RR,1.03;95%CI,1.01–1.05; p ¼ ),
hospital length of stay 421 days(RR,1.29;95%CI,1.16–1.43; p o ).
Time on the ventilator and intensive care unit length of stay were also significantly prolonged for the LVAD þTVP group
JHLT 2014

15. Effect of digoxin on RV function in primary pulmonary hypertension with symptomatic heart failure
17 pts at Rush
No change in HR, no change in PCWP or RA or systemic BP
10% increase CO
Positive inotrope and sympotholytic properties (Decreased NE levels)
1mg IV digoxin given with baseline and 2h hemodynamics recorded
Reduction in NE levels
Recent presentation at ACC regarding effect of digoxin on improving long-term outcomes among patients with PAH
Class IIb (LOE C)
Rich (Rush). Chest 1998;114: 15

16. Effect of PDE-5A inhibition on PVR and RV hemodynamics post LVAD
Control
Sildenafil
PVR (WU)
dP/dtmax/IP
26 pts with persistently elevated pvr following lvad placement
PDE5 improve PVR in pts with LVADs may be started and help to wean iNO
Does not have large effect on mean arterial pressure
Class IIb (LOE C)
Tedford (Hopkins). Circ Heart Fail 2008;1:213

17. Effect of RV pacing on RV function in model of pulmonary hypertension induced RVD
Control
PHTN
RV dP/dt max
Effects of RV pacing in rat model of pulmonary hypertension induced RV dysfunction
PH induced by injection of MCT resulted in PHTN phenotype with RH failure 28 days later
RV pacing improves rv function and diminishes adverse diastolic interaction in rat model
Onset diastolic relaxation impaired. Delay in peak myocardial shortening and delayed onset of rv diastolic relaxation contributes to diminished efficiency of rv contraction and reduced stroke volume,
Rv to lv delay in onset of diastolic relaxation.
Hardziyenk europace 2011; cteph with rvd. Improved stroke volume with rv pacing
RVSP
Class IIb (LOE C)
Handoko. Am J Physiol Heart Circ Physiol 2009:297:H1752

18. Conclusions & Future Directions
RVF post LVAD remains common
Need multi-disciplinary pre-op evaluation
Need data/trials investigate operative techniques
Need trials investigate strategies for management of chronic RVF
Trials of temporary RV MCS support ongoing pre- and post-LVAD
Emerging biventricular mechanical support devices